Chapter 09

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Chapter 9 Genes, chromosomes and patterns
of inheritance
Chapter 10 Nature, structure and organisation
of the genetic material
Chapter 11 Gene function: genes in action
Chapter 12 Manipulating DNA: tools
and techniques
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AREA OF STUDY 1
Heredity
286 NATURE OF BIOLOGY BOOK 1
9
Genes, chromosomes and
patterns of inheritance
KEY KNOWLEDGE
This chapter is designed to
enable students to:
identify how meiosis
generates genetic variability
between offspring of the
same parents
recognise the relationship
between alleles and their
effects on the phenotype
predict outcomes of
monohybrid and dihybrid
crosses
recognise that linked genes
do not assort independently
extend knowledge of the
interplay between genotypes
and the environment
analyse pedigrees and trace
patterns of inheritance.
Figure 9.1 The Adelie penguin at right is visibly different
from the typical Adelie penguins shown at left. This pale penguin
is variously described as an isbelline or leucistic or albinistic
variety. This penguin variety inherited from each of its parents a
faulty genetic instruction for making the enzyme responsible for
pigment production. This and other genetic instructions or genes
are carried on structures known as chromosomes. In this chapter
we will explore the behaviour of chromosomes and of the genes
that they carry and will examine patterns of inheritance from
parents to their offspring.
GENES, CHROMOSOMES AND PATTERNS OF INHERITANCE 287
The genetic lottery
The outcome of the rst pregnancy for Tracey and John was known twins
and the excited parents-to-be were looking forward to the joys and challenges
of parenthood. The pregnancy had proceeded uneventfully. Ultrasonography
showed that Tracey was expecting non-identical twins a girl and a boy
each having developed from a separate fertilised egg and each having a separate
placenta. Ultrasonography also showed that the various internal organs and limbs
of the each fetus were developing normally.
The parents were delighted at the birth of the twins. Tim, the rst-born, had
dark hair, brown eyes and olive skin like his parents. The parents were somewhat
concerned that Fiona, the second-born, showed some unexpected features
including white hair, pink skin and pale-coloured eyes. The doctors advised the
parents that Fiona had a condition known as oculo-cutaneous albinism, in which
pigment is absent from the skin, hair and irises of the eyes.
Tracey and John were relieved to learn that Fionas mental development
would be normal, but were advised that she would be sensitive to the ultraviolet
(UV) component of sunlight because her unpigmented skin would be unable to
produce a tan. This could be managed by minimising exposure to sunlight and
using UV-ltering creams. Other effects of albinism include nystagmus (rapid
involuntary eye movements), reduced visual acuity and photophobia (extreme
discomfort in bright light), which could be managed with prescription glasses.
The parents were anxious to know more about albinism and were referred for
genetic counselling. The counsellor explained that the condition was not due to
any environmental factors, such as medication taken by Tracey during her preg-
nancy, but was an inherited condition.
As there was no history of albinism in either of their families, Tracey and John
were keen to nd the answers to questions such as:
How can our child have albinism when we both have normal pigmentation and
when there is no history of this condition in either of our families?
Could our next baby be affected by this condition?
Could grandchildren be affected by albinism?
Some conditions are more common in males than in females, so does the sex
of a baby inuence the likely occurrence of albinism?
A neighbours friend recently had a child with Down syndrome. What is the
cause of this condition?
Inherited variations
Albinism also occurs in a range of vertebrates, including mammals (for example,
albino koalas and kangaroos), birds (albino budgerigars, ravens and kookaburras)
and reptiles (albino snakes and alligators) (see gure 9.2).
Pigment production in vertebrates, including people, is under genetic control
and so is an inherited condition. In order to make pigment, an enzyme, known
as tyrosinase, must be present. This enzyme is a protein whose production is
controlled by a specic genetic instruction, or gene, passed on to an offspring
by each parent. If both parents transmit a faulty genetic instruction to their off-
spring, such as occurred in the case of baby Fiona, an altered protein that cannot
act as tyrosinase enzyme results. Therefore, pigment production cannot occur,
leading to albinism.
Gametes: packages of genetic instructions
A child receives an estimated 20 000 to 25 000 genetic instructions from each
parent. The double set of genetic instructions, one set from the mother and one
set from the father, affect the child throughout its life, long after the parents are
ODD FACT
Famous people
showing albinism include
the Rev. Dr W. A. Spooner
(18441930), Warden of New
College, Oxford, whose speech
transpositions are now known
as spoonerisms, as for example,
saying blushing crow instead
of crushing blow.
The box on page 290 describes the
work of a genetic counsellor at the
Royal Childrens Hospital, Victoria.
Figure 9.2 (a) An albino baby koala (b) An albino kookaburra
(c) An albino family that in the late 1800s exhibited themselves at circuses
Figure 9.3 An egg cell with sperm cells adhering. Each of these cell types
carries one set of genetic instructions.
ODD FACT
Plato (427347 BC)
thought that semen, which
contains sperm cells, was
produced in the brain. This idea
was still current in 1720, when
one author wrote: Semen . . .
is chiey supplied by the brain
and carried through innumerable
channels to the testicles.
dead. The child will itself transmit to any of its future offspring a set of genetic
instructions selected from its own double set. All this involves gametes.
The set of genetic instructions that pass from mother to offspring is packaged
in the nucleus of her egg cell and the set from a father is packaged into the
nucleus of a sperm cell (see gure 9.3). The term gamete refers to both egg and
sperm cells. Gametes, and the cells that give rise to them, are called germline
cells.
After fertilisation, the nucleus of the sperm cell fuses with the nucleus of the
egg cell to form the nucleus of the fertilised egg which contains the double set of
instructions for a unique individual. The only exception to this are identical twins
(or higher multiples) which result from cells derived from a single fertilised egg
and so share the same genetic instructions.
Gametes are the only cells that can naturally cross the generation gap. All the
other cells that make up a multicellular organism are known as somatic cells and
they die when the organism dies. A continuity exists between parents and their
children, and between them and their childrens children, and so on, across the
generations. The link across generations is through the chemical compound
deoxyribo nucleic acid (DNA), the material of the genetic instructions or
genes, and these are transmitted between generations by gametes.
Genetic instructions within your cells include some that have been
passed down from your great-great-grandparents and earlier genera-
tions, who may have been born in another part of the world.
The double set of genetic instructions present in an organism
makes up its genotype. A particular genotype is generated when an
egg is fertilised by a sperm. The visible expression of the genotype
in the physical, biochemical and physiological characteristics of
a person is called the phenotype. In gure 9.4, one feature of the
phenotype seen in most family members is a distinctive pointed
hairline, known as a widows peak. Do you have a widows peak or
is your hairline straight? Other examples of phenotypes are traits such
as blood group A, ability to make pigment and colour blindness.
(a) (b) (c)
Figure 9.4 This gure shows
two parents, their only daughter
and their seven sons. Most show a
widows peak hairline. Parents are
physically linked to their children
through the genetic material that
they pass on to them in their
gametes.
Gonads: where instructions are
packaged into gametes
The ovaries of females and the testes of males are specialised organs, known as
gonads. These organs are the sites where the double set of genetic instructions is
halved and packaged into gametes (see gure 9.5). The halving occurs through
meiosis (see pages 3034).
(a)
(b)
Figure 9.5 Photomicrograph showing the cross-sections
of: (a) normal mammalian testis with mature sperm inside
the tubules of the testis, and (b) testis from an infertile
male with no mature sperm but showing evidence of cell
death (apoptosis) where brown stain appears
BIOLOGIST AT WORK
Lisette Curnow genetic counsellor
When I completed my degree in biological science,
I knew that, while I enjoyed laboratory work and had a
real interest in science, especially genetics, I couldnt
see myself in the lab long-term. Having heard about
genetic counselling as an emerging profession, I liked
the idea of combining my genetic interest with dealing
with people in a clinical setting. The role of a genetic
counsellor is to provide accurate information and
options, together with counselling and support to indi-
viduals or families whose lives are impacted in some
way by a genetic condition in themselves, their children
or their extended family. It is a particularly important
eld given the dramatic advances that are being made in
genetics, and complex information needs to be imparted
to the public in a clear and concise way.
The convenor of the Post Graduate Diploma in Genetic
Counselling (run through Melbourne University) rec-
ommended that I try to develop some counselling skills
to see if that was something I would like to do. I volun-
teered at Lifeline, a telephone counselling service that
puts volunteers through a fairly comprehensive training
program, an experience that I found to be invaluable
in determining whether I was interested in counselling
and had any skills in the area. I subsequently completed
the Graduate Diploma in genetic counselling, then
travelled for 12 months, combining backpacking with
six months of work experience at the Hospital for
Sick Children in Toronto. On my return to Melbourne,
I took up some volunteer work before embarking on
my Master of Health Sciences (Genetic Counselling)
degree. This gave me a real interest in research and I
developed skills I have been able to use in my job.
While completing my masters, I worked part-time in
cancer genetics at Peter MacCallum Cancer Institute.
This work involved meeting with individuals with a
very strong family history of cancer to assess whether
or not they may carry an inherited mutation in one of
the cancer-predisposing genes. While testing for cancer
predisposition is still limited, it may be available for
families who meet high risk criteria for breast cancer
and some forms of bowel cancer. Assessment of people
to see if they meet these criteria is done by genetic coun-
sellors and other relevant clinicians (such as geneticists,
oncologists, gastroenterologists and breast surgeons)
through the various cancer genetics services.
I later worked in developing cancer services at the
Royal Childrens Hospital before moving into my
current role in 2000 as genetic counsellor to the Royal
Childrens Hospital. This job is varied and challenging
two reasons that I enjoy it so much. Part of my role
involves dealing with abnormal cystic brosis results
from Newborn Screening (the heel-prick test that is
carried out on every baby born in Victoria a couple
of days after birth). This involves contacting families
to bring their new babies in for further testing. I also
attend the weekly paediatric clinic where I see a range
of patients, such as families who may have a child with
a new diagnosis of a genetic condition, or a family
member who is concerned about their risk of being a
carrier of a condition that is present in the family. I am
also fortunate to be involved in coordinating the genetics
component of the Graduate Diploma in Genetic Coun-
selling, as well as frequently giving lectures to various
groups. Finally, I squeeze as much research as possible
into my schedule as I am perfectly positioned to access
valuable information regarding the impact of todays
genetic technology on the public.
Our genetic knowledge is constantly evolving and,
as genetics does not discriminate, the families we meet
are necessarily varied and multifaceted. This ensures
that there is rarely a dull moment in my day-to-day
work. The interpreting of complex genetics and tech-
nology to the people it affects every day is an extremely
challenging yet rewarding eld in which to work.
Figure 9.6
Lisette Curnow
Chromosomes: gene carriers
Genetic instructions are present in the DNA in the nucleus of each somatic cell.
Each different instruction is a specic gene made of DNA. Genes are organised
into larger structures known as chromosomes with each chromosome carrying a
large number of genes (see gure 9.7).
Genetic instructions are packaged in gametes (either eggs or sperm
cells) for transmission from parents to offspring.
Each parent contributes a set of genetic instructions to its offspring so
that the offspring inherits a double set.
Genetic instructions consist of genes that are made of DNA.
The genetic instructions comprise the genotype of an organism.
The phenotype is the physical, biochemical or physiological expression
of the genotype.
In animals, egg and sperm cells are formed in specialised organs called
gonads ovaries in females and testes in males.
KEY IDEAS
1 What material can cross the generation gap?
2 Where does egg formation occur in females?
3 What percentage contribution is made by each parent to the genotype
of an offspring?
4 True or false? Briey justify.
a A child could inherit genetic instructions that were present in its
great-great-grandparent.
b An inherited characteristic such as hairline shape or blood type is
part of a persons phenotype.
c A gamete is a gonad.
QUICK-CHECK
Figure 9.7 Scanning electron
microscope image of double-stranded
chromosomes
Chromosomes: how many?
Each species has a characteristic number of chromosomes in its somatic cells; for
humans, this number is 46. This number is often denoted as 2n and is referred to
as the diploid number. Table 9.1 provides data on some other species. Gametes
contain half the diploid number, the haploid number (n).
Human chromosomes
Figure 9.8a shows the chromosomes from a normal human male as viewed
through a microscope. To assist analysis, the complete set of chromosome images
is organised according to an international convention to form a karyotype (see
gure 9.8b). The 46 human chromosomes from a normal human male can be
arranged into 23 pairs of chromosomes, consisting of 22 matched pairs and one
odd pair that is made up of one larger X chromosome and a smaller Y chromo-
some. In a normal female, a similar arrangement is seen, except that there are two
X chromosomes and no Y chromosome. The pair of chromosomes that differs
between the sexes makes up the sex chromosomes. A shorthand way of denoting
the pairs of chromosomes for each sex is as follows normal human male:
46, XY, and normal female: 46, XX. (Note that the number indicates the total
number of chromosomes including the sex chromosomes and the letters denote
the sex chromosomes.) A similar pattern is seen in other mammals where the
female typically has two X chromosomes and the male has one X and one Y
chromosome. This is not the case in other animal groups.
The 22 matched pairs of chromosomes present in both males and females are
termed autosomes. These different autosomes can be distinguished by:
their relative size
the position of the centromere, which appears as a constriction along the
chromosome. In some cases, the centromere is near the middle (for example,
the number-2 chromosome in gure 9.8b), while in others it is close to one end
(for example, the number-13 chromosome in gure 9.8b).
patterns of light and dark bands that result from special staining techniques.
ODD FACT
Chromosomes
can be examined before
birth from cells obtained by
chorionic villus sampling or by
amniocentesis (refer back to
chapter 4, pages 10910).
Table 9.1 Diploid number of
chromosomes in somatic cells of
various species. What number would
be expected in sperm and egg cells of
a rabbit?
ODD FACT
The mammal with
the lowest diploid number
is the female Indian muntjac
or barking deer (Muntiacus
muntjac) in which 2n = 6.
ODD FACT
In the early years
of the twentieth century,
published counts of the number
of human chromosomes ranged
from as low as 8 to as high as
50 per somatic cell. It was only
in 1956 that the human diploid
number was nally correctly
identied as 2n = 46.
Species Diploid number (2n)
Animal
chicken (Gallus gallus)
buttery (Lysandra nivescens)
cat (Felis catus)
dog (Canis familiaris)
bilby (Macrotis lagotis)
honeybee (Apis mellifera)
housey (Musca domestica)
leopard seal (Hydrurga leptonyx)
platypus (Ornithorhynchus anatinus)
rabbit (Oryctolagus cuniculus)
eastern tiger snake (Notechis scutatus)
78
190
38
78
19 (male) 18 (female)
32
12
34
52
44
34
Plant
crimson bottlebrush (Callistemon citrinus)
drooping she oak (Casuarina stricta)
edible pea (Pisum sativum)
ginkgo (Ginkgo biloba)
Iceland poppy (Papaver nudicaule)
kangaroo-paw (Anigozanthos avidus)
native rose (Boronia serrulata)
Ovens wattle (Acacia pravissima)
pineapple (Ananas comosus)
river red gum (Eucalyptus cameldulensis)
silky oak (Grevillea robusta)
silver wattle (Acacia dealbata)
Sydney blue gum (Eucalyptus saligna)
tomato (Lycopersicon esculentum)
22
26
14
24
14
12
22
26
50
22
20
26
22
24
Autosomes are identied by the numbers, 1 to 22 in order of decreasing size;
the number-1 chromosomes are the longest, and the number-21 and number-22
chromosomes are the smallest. The larger the chromosome, the more DNA it
contains and usually the greater the number of genes that it carries.
The members of each matching pair of chromosomes, such as the two
number-5 chromosomes, are said to be homologous. Non-matching chromo-
somes, such as a number-5 chromosome and a number-14 chromosome are said
to be non-homologous.
At a particular location along its length, each chromosome has a constric-
tion that is known as a centromere. In human chromosomes, the DNA at the
centromere contains about one million base pairs and much consists of repeated
sequences of bases. Figure 9.9 shows the chromosomes from a dividing white
blood cell where the chromosomes have been hybridised with a pink uorescent
probe that binds to the DNA of the centromere. The centromere is surrounded by
a structure, known as the kinetochore, that is made of protein. The kinetochore
forms the attachment point for the spindle bres that are necessary for the orderly
movement of chromosomes during both cell division (mitosis) and gamete for-
mation (meiosis). This orderly movement of chromosomes ensures that daughter
Figure 9.8 (a) Chromosomes
from the white blood cell of a
normal human male. Are these single
stranded or double stranded?
(b) Karyotype of a normal human
male. How does this differ from that
of a normal female? (c) Ideogram
showing stylised representation of
human chromosomes
1 2 3 4 5 6 7 8 9 10 11 12
13 14 15 16 17 18 19 20 21 22 X Y
ODD FACT
A chemical
extracted from the bulb of a
Mediterranean plant (Colchinium sp.)
can interfere with the formation
of the spindle that normally forms
during cell multiplication (mitosis).
Treatment of cells with this
chemical, known as colchicine,
stops cells at metaphase.
(a) (b)
(c)
Figure 9.11 Various diagrammatic
representations of chromosomes
(a) in the double-stranded condition,
and (b) in the single-stranded
condition. The double-stranded
condition is a temporary state
formed only during part of a cell
multiplication cycle (mitosis) or
during gamete formation (meiosis).
cells formed by mitosis will each have a double (diploid) set of chromosomes
and that gametes formed by meiosis will contain a single (haploid) set of chro-
mosomes.
Human chromosomes, like the chromosomes of other eukaryotes, have dis-
tinctive ends. Chromosome ends are known as telomeres and they consist of
DNA made up of many thousands of repeats of short sequences of base pairs.
In your chromosomes, the repeated sequence is TTAGGG. Telomeres prevent
chromosomes sticking together and they enable complete replication of chromo-
somes to occur.
Analysing karyotypes
Mistakes in chromosome numbers or abnormalities of single chromosomes can
produce congenital disorders. In addition, specic chromosome abnormalities
are associated with various cancers and these chromosome changes can indicate
the likelihood of remission. Scientists who specialise in the study of human
karyotypes are known as cytogeneticists.
Today, in hospital cytogenetic laboratories, images of chromosome sets from
cells are captured by a camera attached to a microscope (see gure 9.10). The
images are then transferred to a computer where a scientist uses special software
such as Cyto Vision to analyse the chromosomes and automatically generates
karyotypes (as shown in gure 9.8, page 293). The chromosomes in a minimum
of 15 cells must be examined before a karyotype can be decided. This computer-
based automation has increased the capacity of hospital laboratories to prepare
the karyotypes that are important in diagnosis of conditions such as Down
syndrome, where an extra number-21 chromosome is present, or Prader-Willi
syndrome, in which a small deletion of the number-15 chromosome occurs.
Figure 9.9 Human chromosomes
with their centromeres made visible
with a probe labelled with a pink
uorescent dye that binds to the
centromeric DNA of all chromosomes.
The remainder of the chromosomes
have been stained with a blue
uorescent dye. Can you identify a
chromosome with a centromere near
the end of the chromosome?
Figure 9.10 A scientist in a
cytogenetic laboratory analyses
a patients chromosomes under a
microscope and studies the display
on a computer screen.
Single or double stranded?
Typically, chromosomes are viewed in somatic cells
that are either naturally undergoing cell multiplication
(mitosis), such as skin broblasts or bone marrow
cells, or from cells that have been articially stimu-
lated to multiply, such as white blood cells. The cells
are treated with a chemical that causes them to stop at
metaphase of mitosis. As a result, photographs of these
chromosomes show them as double stranded, as shown
in gure 9.8 (page 293). Diagrams of chromosomes
can depict them as either double or single stranded (see
gure 9.11).
(a)
(b)
Wrong numbers and other errors
Various changes can occur involving chromosomes, including:
changes in the total number of chromosomes
changes involving part of one chromosome
changed arrangements of chromosomes.
Changes in total number
Some newborn babies have an abnormal number of chromosomes in their cells.
A baby may have an additional chromosome, giving a total of 47 instead of the
normal 46. One additional chromosome or one missing chromosome typically
has deleterious effects on development and, for most chromosomes, death occurs
during early development and the pregnancy never proceeds to term.
A pregnancy may still be carried to term if the chromosomal changes involve
a few particular chromosomes (see table 9.2). The most common chromo somal
anomaly seen in human populations is Down syndrome (DS), in which there is an
additional copy of the number-21 chromosome. When three copies of a chromo-
some occur, instead of the typical pair of chromosomes, a cell or an organism is
said to be trisomic for that chromosome. When one member of the typical pair of
chromosomes is missing, the condition is termed monosomy. Monosomy causes
embryonic death, except for a monosomy involving the sex chromosomes.
ODD FACT
Changes from the
normal diploid chromosome
number in animal species
produce deleterious effects,
often death. In contrast, in
plant species, changes in
chromosome number, such as
from 2n to 4n, often produce a
larger, more vigorous plant.
Chromosome change Resulting syndrome
Approximate
incidence rate
Addition: whole chromosome
extra number-21 (47, +21)
extra sex chromosome (47, XXY)
extra Y chromosome (47, XYY)
Down syndrome
Edwards syndrome
Patau syndrome
Klinefelter syndrome
n/a
1/700 live births
1/3000 live births
1/5000 live births
1/1000 male births
1/1000 male births
Deletion: whole chromosome
missing sex chromosome
(46, XO)
Turner syndrome 1/5000 female births
Deletion: part chromosome
missing part of number-4
missing part of number-5
Wolf-Hirschhorn
syndrome
cri-du-chat syndrome
1/50 000 live births
1/10 000 live births
Table 9.2 Some examples
of chromosome changes and
approximate incidence rates. Which
syndrome is an example of a trisomy?
a monosomy? The XYY condition does
not have a clinical name.
Changes to parts of chromosomes
Changes can occur that involve part of a chromosome, such as:
duplication, in which part of a chromosome is duplicated (see gure 9.12a)
deletion, in which part of a chromosome is missing (see gure 9.12b), as
for example, cri-du-chat syndrome, so named because affected babies have a
cat-like cry (see table 9.2).
Re-arrangements of chromosomes
Structural changes may occur in which the location of a chromosome segment is
altered so that it becomes located to a new region within the karyotype. Such a
change is known as a translocation. One example is related to a special case of
Down syndrome when part of the number-21 chromosome becomes physically
attached to a number-14 chromosome (see gure 9.12c).
deletion: type of chromosome change in which part
of a chromosome is lost (p. 295)
The parental origin of the chromosomes is also important. Normally a child
inherits one member of each chromosome pair from each of its parents. If both
copies of a particular chromosome are inherited from one parent, instead of the
usual one from each parent, abnormalities of development result. For example
Angelman syndrome, characterised by poor motor coordination and mental
retardation, can result if an embryo inherits both of its number-15 chromosomes
from its mother and none from its father.
A case of Down syndrome
Michael (see gure 9.13a) is a young boy who has 47 chromosomes in his body
cells, instead of the normal 46. His karyotype shows the presence of an extra
ODD FACT
An error after
fertilisation can result in an egg
with 46 maternal chromosomes
only. Such an egg develops into
an abnormal structure known
as a teratoma.
Figure 9.13 (a) Michael, then
aged 11, is a DS boy who enjoys using
a computer, which is one of his many
interests. (b) A typical karyotype
from a DS male like Michael. Which
chromosome is present as a trisomy?
Figure 9.12 (a) Normal
chromosome and the same
chromosome showing a duplication
(b) Normal chromosome and the
same chromosome showing a deletion
(c) An example of a 14/21
translocation
Normal
chromosome
Chromosome
with a segment
duplicated
Normal
chromosome
Chromosome
with a segment
deleted
(a) Duplication (b) Deletion
Duplicated
segment
Site of
deletion
Breakage
points
Normal
chromosome 14
Normal
chromosome 21
14/21 translocated
chromosome
(c) Translocation
Breakage
points
New join
21
14
(a) (b)
(a)
2n = 46
21 21
(b)
2n = 47
21 21 21
n = 23
EGG
21
21
n = 24
EGG
SPERM
21
21
21
SPERM
n = 23
n = 23
Fertilisation
Fertilisation
number-21 chromosome, which is typical of the condition Down syndrome. This
karyotype can be denoted as 47, XY, +21 (where 47 denotes the total number
of chromosomes, XY denotes the sex chromosomes present, and +21 denotes
the identity of the extra chromosome).
About one in 700 babies born in Australia has an extra
number-21 chromosome, but the rate differs according to the
age of the mother (see gure 9.14). The risk of having a DS
baby increases with maternal age; the risk for mothers aged 20 is
about 1/2300 while the risk for mothers aged 40 is about 1/100.
The presence of an extra number-21 chromosome produces
various symptoms including a fold on the inner margin of the
upper eyelid, a smaller than normal mouth cavity and distinctive
creases on the palms of the hands and the soles of the feet.
The trisomy condition in which three separate copies of the
number-21 chromo some are present in the karyotype is the
most common form of DS. In most cases, the extra number-21
chromosome is transmitted via an abnormal egg with 24 chromo-
somes, including two number-21 chromosomes. If this egg is fertilised by a
normal sperm (with 23 chromosomes including one number-21 chromosome), a
DS embryo will result (see gure 9.15).
Figure 9.14 Incidence of DS births
for mothers of different ages. How
does the risk of a DS baby for a
40-year-old woman compare with
that of a 20-year-old? Increased
fathers age also increases the risk,
but to a lesser extent.
20 25 30 35 40 45
0.03
0.02
0.01
0.00
F
r
e
q
u
e
n
c
y

o
f

D
S
p
e
r

l
i
v
e

b
i
r
t
h
s
Age of mother
1
2300
1
880
1
290
1
100
1
46
Figure 9.15 (a) Fertilisation of
normal gametes (b) Possible gametes
involved in fertilisation to produce a
DS zygote. (In both (a) and (b), the
number-21 chromosomes are shown
separately.)
An abnormal egg results when, during the process of egg formation by meiosis
in the ovary, the normal separation of the two copies of the number-21 chromo-
some does not occur. This type of error is known as a non-disjunction, and is
unpredictable. For parents who have a DS child that is a result of non-disjunction
during egg formation in the mother (or during sperm production in the father),
the risk of a second child with DS is low and is determined by the mothers age.
When a child with DS is born, new challenges arise for the family concerned.
Read the following box about Jane, a young woman with DS, as told by her
mother.
Jane is the third of four children born into our family.
When she was born 31 years ago, little did we realise
the extent to which our ideas about disability and life
chances would change. At the time of her birth, we
were shocked, saddened and confused about what it
might mean to have a child with Down syndrome. We
didnt know very much about it; however, we were for-
tunate to have doctors who provided us with as much
information as possible and urged us to treat her just
like any other baby. Jane received the same attention,
the same love and the same opportunities for learning
and socialising that her brothers experienced.
Janes early development proceeded through the
same stages as for most other children, but more
slowly. For example, she sat up at 10 months, crawled
at 15 months, walked when she was 26 months old and
talked by the time she was three and a half. We came
to believe that Jane could learn to do most things that
other children learn, but that the learning process would
take longer. She was happy to sit and watch others, but
wouldnt necessarily initiate action as much as other
children do, so we ensured that Jane was actively
involved in as many play experiences as possible.
When Jane was three and a half, she attended a Day
Training Centre for the Intellectually Handicapped, as
such centres were called then. She became involved
in the usual kindergarten activities such as music,
painting, solving jigsaws and so on. However, she was
still doing much the same things two years later and her
opportunities for academic learning were very limited.
We believed that Jane was capable of learning much
more than was expected of her at the centre. When Jane
was ve, she had the opportunity of attending the local
kindergarten for two days a week where she socialised
with children with a much broader range of abilities.
At the age of six, Jane began to learn how to read.
Having been a primary teacher, I decided to teach Jane
at home and was delighted to nd that she learned with
relative ease. From then on, we learned never to assume
what Jane may or may not be capable of learning, but
always to provide opportunities for her to learn. At this
time the integration debate began, and it reinforced my
conviction that Jane should be able to attend her local
school with her brothers and neighbourhood peers. So
when Jane was seven, she was admitted along with
other school beginners at our local school and had her
needs met in the same way as theirs. Although Jane was
two years older than most of the other children, she was
very small and was at their level developmentally, so
her placement was appropriate.
PERSONAL STORY
Janes story, as told by her mother
In looking for secondary school options for Jane,
we were delighted when she was accepted into a small
Catholic girls school that catered for individual dif-
ferences in an inclusive way. Jane attended secondary
school for ve years, after which time the work was
becoming too complex and difcult for her, so a job
placement seemed to be a more appropriate option.
Having been integrated into the mainstream of edu-
cation, we believed Janes options for integration into
the workforce were considerably broadened. Since
leaving school she has been employed in fast-food busi-
nesses including McDonalds and also in retail stores.
For the past eight years she has been employed in a
Target store under a productivity-based pay scheme,
whereby she is paid according to her level of produc-
tivity, which is measured against the average worker.
Under this scheme, she receives a disability pension
reduced according to her wage.
Jane knows that she has Down syndrome and has
a simple understanding of what that means geneti-
cally, but she doesnt see herself as disabled because
she can learn to do so many things that other people
learn. Indeed, she continues to learn and has reached a
level of independence that we would not have believed
possible.
She has had piano lessons and has always been inter-
ested in TV, books, music and dancing. She is capable
of travelling to and from work, shopping by herself,
operating quite complex video, DVD and Internet tech-
nology, arranging social outings with her friends and
making appointments for herself. Jane is currently
having lessons on cooking and budgeting to enable
her to take the next step towards greater independence.
Although Jane received her L plates ready for driving
lessons, she didnt in fact take them. The important
thing is that she did have the opportunity to learn.
Figure 9.16
Jane in 2005
Another form of DS: translocation
Each year in Australia, a few babies are born that show all the clinical signs of
DS. Their karyotype, however, shows just 46 chromosomes, instead of the 47
expected in DS. So, what has happened?
In these cases, a third number-21 chromosome is present, but it is not a separate
chromosome. Instead, the extra number-21 is joined to another chromosome, for
example, the number-14 chromosome, through a translocation (see gure 9.17).
As a result, the total number of chromosomes in somatic cells of this rarer form
of DS is 46.
Baby Leanne has DS. Examination of her chromosomes showed a total of
46 chromosomes. The third copy of the number-21 chromosome is attached to
one of her number-14 chromosomes. This type of DS is called translocation-DS,
because the extra number-21 chromosome has been transferred to an unusual
location on another chromosome.
When a translocation-DS baby is detected, the chromosomes of its parents are
also investigated because many cases of translocation-DS are inherited. When
this is the case, one of the parents is found to have 45 instead of the expected
46 chromosomes (see gure 9.17) because this parent has one of the number-21
chromosomes translocated to another chromosome. In these cases, the chance
that the next child will be affected is theoretically about one in three but in reality
is about one in 10.
Figure 9.17 A translocation form
of Down syndrome in which the
condition is inherited. Note that the
mother can produce four kinds of egg
in terms of their chromosomal make-
up. Baby Leanne resulted from the
fertilisation of an egg of type C with
a normal sperm. What would result
when an egg of type B was fertilised?
A fertilised type-D egg would die.
Why?
ODD FACT
About 92 per cent
of cases of DS are
trisomy-21 and about
4 per cent are translocation DS.
The remainder are mosaic DS
with a mixture of normal cells
and trisomy-21 cells.
45
Type A Type B Type C Type D
Total
number of
chromosomes
Leanne's
parents
View of
number-14 and
number-21
chromosomes Possible gametes
46
14 21 14/21
14 14
21 21
14
21
Chromosomes and sex determination
The wife of King Farouk of Egypt had given birth to three healthy daughters. In
1948, Farouk divorced his wife because she had not produced a male heir. Was
this reasonable?
In mammals, birds and some reptiles, the sex chromosomes are important
in determining sex. This is because they carry certain genes that are critical in
sex determination, such as the SRY gene on the mammalian Y chromosome,
which controls testis formation. This mode is known as genetic sex determi-
nation (GSD) (see table 9.3).
Animal group Chromosome system
mammals and some reptiles XX female; XY male
birds and some reptiles WZ female; ZZ male
some insects XX female; XO male
Table 9.3 Genetic sex determination
involving sex chromosomes
Mammals: the XX/XY system
The sex of a human fetus can be predicted before birth on the basis of the sex
chromosomes present two X chromosomes indicate a female, while one X
and one Y chromosome indicates a male. A similar XX/XY situation applies
with a few rare exceptions to other mammals. All the normal eggs produced by a
human female during meiosis will contain one X chromosome as well as 22 non-
homologous autosomes. In contrast, male mammals produce two kinds of sperm.
All normal human sperm have 22 non-homologous autosomes but some carry
one X chromosome and others carry one Y chromosome (see gure 9.18).
ODD FACT
As expected,
female swamp wallabies
(Wallabia bicolor) are XX but
normal males are exceptional
in that they have one
X chromosome and two
Y chromosomes one smaller
one (denoted Y
1
) and
one larger one (Y
2
).
Figure 9.18 Which parent
determines the sex of a baby?
Was King Farouk (page 299)
reasonable in divorcing his wife?
Meiosis
Eggs
Its a girl!
Its a boy!
Sperm
Meiosis
22 + X
22 + X
22 + X
22 + Y
22 + Y
22 + X
22 + X
22 + X
46
44 + XY
46
44 + XY
46
44 + 2X
46
44 + XX
The WZ/ZZ system
Sex chromosome differences also occur in birds but the arrangement is different
from mammals. Male birds have two similar sex chromosomes that are known
as Z chromosomes. In contrast, the pair of sex chromosomes in female birds
comprises one W and one Z chromosome, and so it is the female parent in these
groups that determines the sex of the offspring.
This WZ/ZZ genetic system of sex determination is also seen in some reptiles,
such as snakes and monitor lizards (e.g. goannas), and in amphibians, such as
some frog species. Tiger snakes (Notechis spp.), for example, have a total of 34
chromosomes with males having two Z chromosomes and females having one Z
and one W chromosome.
Reptiles other means
It was discovered that, in some reptiles, the sex of offspring depends on the
incubation temperature of the eggs. This is an example of environmental sex
determination (ESD), and is seen in green turtles (Chelonia midas) (see gure
9.19). Female turtles lay an average of 110 eggs and bury them in the sandy
beaches along Australias tropical coastline. After laying, the female turtles
return to the sea. Male turtle hatchlings result from eggs that are incubated
at high temperatures (above 31C), female hatchlings are produced when the
incubation temperature is lower (27C and below), while at intermediate
temperatures (around 29 C) about equal numbers of both sexes are produced.
ODD FACT
We tend to think
of sex as determined for life, but
individual sh of several species
have the ability to change
sex during their lifetimes (see
Nature of Biology Book 1 Third
Edition, page 190).
Crocodiles also have ESD. Crocodiles lay their eggs in a mound of mud and
vegetation that produces heat as it rots. The mother guards her nest and monitors
its temperature. If the temperature rises too much, she pushes away some of the
vegetation cover. If the temperature falls too low, she adds more vegetation to
the mound.
Chromosomes are organised collections of genes.
Each species has a characteristic number of chromosomes, known as
the diploid number, typically present in body (somatic) cells.
Human chromosomes in body cells exist in pairs, normally 23 pairs.
The 23 pairs of human chromosomes include 22 pairs of autosomes
present in both sexes, and one pair of sex chromosomes, XX in the
female and XY in the male.
Additional or missing entire chromosomes or parts of chromosomes
typically produce deleterious effects.
Various mechanisms of sex determination exist in Kingdom Animalia.
KEY IDEAS
5 Distinguish between the terms: autosome, sex chromosome and
chromosome.
6 Two chromosomes are homologous. Could they be:
a two number-9 chromosomes?
b a number-4 and a number-20 chromosome?
7 A biologist examined human cells showing chromosomes. Could the
sex of the person from whom they came be identied? Explain.
8 What is the condition 47, +21?
QUICK-CHECK
Figure 9.19 Green turtle
hatchlings emerge from a nest
in the sand of a northern
Queensland beach.
Meiosis: diploid to haploid
Human body cells contain the diploid number of 46 chromosomes (22 pairs of
autosomes and one pair of sex chromosomes). Egg and sperm cells each have 23
chromosomes, where 23 denotes the haploid number (n = 23), consisting of 22
non-homologous autosomes and one sex chromosome (X or Y).
Meiosis is the process that produces gametes with half the number of
chromosomes seen in somatic cells, that is, half the diploid number. After
fertilisation, when the egg nucleus and the sperm nucleus fuse, the diploid
number of chromosomes is restored (see gure 9.20).
The chromosomal dance of meiosis
In mammals, in females, the process of meiosis of one precursor cell produces
just a single functional egg. In contrast, in males, the products of meiosis of a
precursor cell are four functional sperm (see gure 9.21).
Haploid egg
23
Diploid zygote
46
Haploid sperm
23
n n 2n
Figure 9.20 Fusing of a sperm
nucleus with an egg nucleus restores
the typical number of chromosomes.
The key outcomes of meiosis are as follows:
meiosis halves the chromosome number, reducing it from diploid to haploid;
as a result, each gamete contains just one member of each homologous pair of
chromosomes (see gure 9.22a)
meiosis produces random combinations of the members of the different
homologous chromosome pairs; as a result, in a large number of gametes, any
member of one homologous pair can be found with any member of the other
homologous pairs (see gure 9.22b)
meiosis splices parts of one chromosome with its partner homologue; as a
result, gametes contain chromosomes with new genetic combinations differing
from those in the precursor cell (see gure 9.22c).
Figure 9.23 (page 304) shows the various steps of meiosis and how this process
juggles chromosomes and the particular forms of the genes that they carry.
OGENESIS
(egg formation)
ovum (egg) polar bodies
SPERMATOGENESIS
(sperm formation)
sperm
Figure 9.21 The formation of eggs
and sperm by meiosis. Note that only
one egg is formed but four sperm are
produced from each starting cell.
Meiosis: source of variability in offspring
The biological signicance of meiosis is that it produces variability among
the offspring produced by sexual reproduction involving gametes from two
parents. No two offspring are the same! In contrast, asexual reproduction, in
which one parent organism gives rise to offspring through the process of meiosis,
produces offspring that are genetically identical with each other and with the
parent organism.
A litter of kittens may consist of a seemingly odd mixture of colours and
patterns (see gure 9.24, page 305). Siblings (brothers and sisters) in a human
family can show differences in hair colour, eye colour, blood types and other
phenotypic traits. Inherited differences between offspring can be traced back to
the process of meiosis and to the genetic variation that this process produces in
gametes.
Recombination produces variation
Gametes carry unique genetic combinations because of crossing over between
homologous chromosomes and because of independent disjunction of chromo-
somes during meiosis. This re-assortment of genetic material to produce new
genetic combinations is known as recombination and is a major cause of vari-
ation in offspring of the same parents.
We can get some idea of the variation produced by sexual reproduction if
we consider organisms with just two pairs of chromosomes (2n = 4) (see gure
9.25, page 305). Ignoring crossing over, the female parent can produce gametes
with four different combinations of chromosomes: A
1
B
1
and A
1
B
2
and A
2
B
1
and
A
2
B
2
. Likewise, the male parent can produce four combinations, including A
3
B
3
.
Can you identify the other three combinations? Consequently, the chance that
two offspring will receive the same chromosomal combinations from their two
parents is 1/4 1/4 = 1/16. The probability that offspring will receive different
chromosomal combinations from their parents is 15/16.
Input: Cells with genotype Aa Bb
A a
B b
A a
B b
AB AB Ab Ab
aB aB ab ab
MEIOSIS
Output: Cells with random combinations
of alleles. One allele only of each gene is
present in each gamete.
(b) Input: 1 cell with 2 pairs of
homologous chromosomes
(a)
MEIOSIS
Output: 4 cells with one member
only of each pair of homologues
Input: 1 cell with 1 pair of
homologous chromosomes with
2 linked genes
MEIOSIS
Output: 4 cells, some with splicing
of homologous chromosomes to
create some new gene combinations
(c)
A a
D d
A
D
A
d
a
D
a
d
Figure 9.22 Meiosis: the halving and mixing machine (a) The halving is precise one member of each pair of chromosomes
appears in the cell products. (b) Meiosis produces cells with random combinations of the alleles of each separate gene on non-
homologous chromosomes. (c) During meiosis, exchange of segments can occur between homologous chromosomes. This is known as
crossing over.
Asexual reproduction is covered in
detail in Nature of Biology Book 1,
Third Edition, pages 17683.
1. Starting point: cell with two pairs of single-stranded
homologous chromosomes (2n = 4).
2. Early in meiosis, each chromosome replicates
to become double stranded.
3. The homologous chromosomes align and pair closely
or synapse. One or more exchanges or crossovers
occur between a matching segment of one
chromosome with a strand in its paired homologue.
Crossing over produces new combinations of genetic
instructions. The chromosomes then line up across the
equator of the cell. Different arrangements are
possible.
4. The homologous chromosomes separate (disjoin) from
each other when their centromeres are pulled to
opposite poles. The disjunction of each homologous
pair is independent of any others. (For example, if the
red chromosome goes to the left-hand side, this in no
way influences which of the longer chromosomes will
go to the right-hand side.)
5. The resulting two products each have two
double-stranded chromosomes, one long and one
short.
6. The strands of each replicated chromosome then
disjoin so that the single-stranded chromosome moves
in opposite directions. The separation of the
single-stranded copies of each chromosome is
independent of that of other chromosomes.
7. End point: typically, four cells result from meiosis with
each end product containing the haploid number of
chromosomes. Having started from one cell (2n = 4),
the process has produced four cells, each n = 2.
Note the variation between end products.
1.
2.
3.
4.
5.
6.
7.
A
A
E
E
e
e
b
b
B
B
a
a
A
E e
E E e e
e e
b B
a
b B b B
A A a a
b B
a a
b
b A
A
E
B
e
e
B
A A
E E
a
a
B
b
E
A
b
e
e
B
A
a
B
E
E
b
a
Stages shown are:
1, 2, and 3
prophase 1
4 metaphase 1
moving into
anaphase 1
5 telophase 1
moving into
prophase 2
6 anaphase 2
7 telophase 2
Figure 9.23 Stages in the process of meiosis, from the starting diploid cell to the nal haploid gametes. In human females,
only one of these four cells will result.
Table 9.4 shows how the variation in sexually reproducing species increases
with increasing numbers of chromosomes.
Table 9.4 Probabilities of two offspring receiving identical or dissimilar chromosomal
combinations from parents. What happens as 2n increases? (If crossing over is included, the
chances of identical combinations are even lower.)
Diploid number
of chromosomes
Chance of receiving
identical chromosomal
combinations
Chance of receiving
different chromosomal
combinations
2n = 4 1/16 15/16
6 1/64 63/64
8 1/256 255/256
10 1/1024 1023/1024
When fertilisation of genetically variable eggs and sperm occurs, the results
are offspring with genetic combinations that differ from each other and from
those of their parents (see gure 9.26). In contrast, in organisms that reproduce
asexually, the offspring are identical with each other and identical to the single
parent that produced them.
When meiosis goes wrong
Occasionally, a pair of chromosomes fails to disjoin so that two copies of a
chromosome rather than the usual one are present in a gamete formed by meiosis.
The failure to separate is called non-disjunction, which is an unpredictable
error. Non-disjunction can occur at either step 4 or 6 of meiosis (see gure
9.23, page 304). In the trisomy form of DS, the number-21 chromosomes fail to
disjoin.
Figure 9.24 Kittens from two parents show variation in colour and pattern.
Female parent Male parent
A
1
A
2
B
1
B
2
A
3
A
4
B
3
B
4
Figure 9.25 Homologous
chromosomes in an organism.
The homologous pairs are colour
coded.
Figure 9.26
Genes: inherited instructions
The genetic instuctions that we inherit from our parents consist of a collection
of genes. A gene is an inherited instruction made of DNA. Genes control various
structures and functions. One human gene controls the type of collagen present
in bone and cartilage. Another controls the production of Factor VIII, a sub-
stance essential for blood clotting. Yet another gene controls the production of
the enzyme, tyrosinase, whose absence causes albinism.
How many genes?
The human genetic material comprises an estimated 20 000 to 25 000 different
genes. So far, several thousand of these genes have been identied and they are
listed in a reference book Mendelian Inheritance in Man (MIM). Because the
rate of identication has become so rapid, the list has been made into a computer
database called OMIM (Online Mendelian Inheritance in Man). This has two
main advantages:
A computer database can be updated and revised as soon as each new gene is
identied; revisions of a book must wait until the next printing.
Information from the database can be obtained easily and quickly using
a personal computer and phone link to the US Medical Library where the
database is maintained.
Naming genes
Genes can be named after the functions they control, such as the gene control-
ling Rhesus blood type. For convenience, genes are given shorter identiers.
9 Typical somatic cells in dogs (Canis familiaris) contain 78
chromosomes. How many chromosomes would be expected in:
a the normal egg of a female dog?
b a fertilised egg?
c a cell with a trisomy?
10 Which chromosome is involved in non-disjunction in Down syndrome?
11 a Does crossing over increase or decrease the variation in one
persons gametes? Explain.
b How many normal disjunctions occur in meiosis?
QUICK-CHECK
During meiosis, gametes with a haploid set of chromosomes are formed.
Normal human eggs contain 22 different autosomes and one
X chromosome.
Normal human sperm contains 22 different autosomes and either one
X chromosome or one Y chromosome.
Normally only one member of each pair of chromosomes goes into a
gamete.
Variation between gametes of one person arises from exchanges during
crossing over and from random disjoining of chromosomes.
Non-disjunction leads to gametes with abnormal numbers of
chromosomes.
KEY IDEAS
Just as a young boy named Benjamin James McDonald is called Ben, so scien-
tists have developed a shorthand scheme for naming genes. In this scheme, genes
are usually given a name consisting of a group of up to ve characters (capital
letters or numbers), with the rst character always being a letter (see table 9.5).
Table 9.5 A few human genes.
In this book the names of genes will be
shown in bold type.
ODD FACT
It was only in 1968
that the rst autosomal gene
was assigned to a particular
chromosome, namely the
Duffy blood group gene to the
number-1 chromosome.
Gene Chromosome location Gene function
ABO 9 controls ABO blood type
ACH 4 controls production of broblast growth
factor receptor; abnormal form results in
achondroplasia, a type of dwarsm
BRCA1 17 controls an early onset form of breast cancer
CFTR 7 controls nature of mucus and secretions from
various glands
DMD X controls production of the muscle protein,
dystrophin
F8C X controls ability to produce Factor VIII,
a blood-clotting factor
HBB 11 controls production of beta chains of
haemoglobin
HD 4 controls production of huntingtin; an
abnormal form of this gene results in
Huntington disease
PKU1 12 controls production of phe hydroxylase
enzyme
RH 1 controls Rhesus blood type
TYR 11 controls production of enzyme, tyrosinase,
needed for pigment production
Location of genes
We have seen that genes do not oat freely in cells, like peas in soup, but are located
on chromosomes that are found in the nuclei of eukaryote cells. The position
occupied by a gene is its locus (plural = loci), which is like its address. A simple
analogy is to think of a chromosome as a residential street with a large number of
houses. Each house is like a gene, and its address corresponds to its locus.
The HBB gene locus is near the end of the short arm of chromosome 11. The
EGFR gene has its locus near the centromere of chromosome 7. A chromosome
drawing showing some of the gene loci that it carries is called a chromosome
map (see gure 9.27).
Figure 9.27 Map of some human
chromosomes showing a few gene
loci (some of these genes are
discussed in the text). The region
in which a locus is positioned is
identied by a system, such as 7q31
or Xp2, where:
the rst number (or letter)
identies the chromosome
the letter p or q denotes the
chromosome arm, with p = short
(from the French petit) arm and
q = long arm
the nal number identies the
region of the chromosome arm.
p
p
q
q
1
1
1
2
2
3
1
2
3
4 7 9 11 X
HD
ACH
EGFR
CFTR
TCRB
p
q
1
1
2
2
3
FRDA
ABO
ABL
p
q
1
1
2
HBB
TYR
p
q
1
2
1
2
DMD
FMR1
F8C
Tall
(D)
Dwarf
(d )
Chromosome number 1 Chromosome number 2
Chromosome
number 7
Smooth
(P )
Peach
(p )
Woolly
(Wo )
Normal
(wo )
Simple
inflor. (S )
Compound
inflor. (s )
Non-beaked
(Bk )
Few locules
(Lc )
Beaked
(bk )
Many locules
(lc )
Red
(R )
Green-base
(U )
Smooth
(H )
Non-tangerine
(T )
Xanthophyllous
(Xa)
Yellow
(Wf )
Yellow
(r )
White
(wf )
Uniform fruit
(u )
Hairy
(h )
Tangerine
(t )
Green
(xa )
An average human chromosome carries a large number of genes, arranged
in a particular linear order. The larger a chromosome, the more genes it carries.
Table 9.6 gives information about some larger and some of the smaller human
chromosomes in terms of their size (expressed in the number of base pairs in the
chromosomal DNA) and the likely number of genes that they carry.
Figure 9.28 Linkage groups in
the tomato Lycopersicon esculentum.
A linkage group corresponds to the
genes on one chromosome.
Table 9.6 Information about the size and likely number of genes carried on some of the human chromosomes
Chromosome
Number of base pairs
in the chromosomal DNA
Likely number of
genes on chromosome
One of the disease-related genes
on chromosome
1 246 million bps 2100 to 2600 genes FHC31 familial hypercholesterolemia
5 181 million bps 900 to 1300 genes F12 factor XII deciency
21 47 million bps 200 to 400 genes APP Alzheimer disease 1
X 155 million bps 900 to 1200 genes FRM fragile X syndrome
Y 50 million bps 70 to 300 genes USP9Y azoospermia
Genes located on one chromosome are members of the same linkage group.
Figure 9.28 shows three of the linkage groups in the tomato. The total number of
linkage groups is typically equal to the haploid number of chromosomes. So, the
tomato with a diploid number of 24 has 12 linkage groups. In humans, however,
there are 22 autosomal linkage groups plus the X- and Y-linkage groups. Refer
back to gure 9.27 to see a few of the genes in some human linkage groups.
For a detailed chromosome map,
check out gure 10.43 on
page 368.
Unusual locations
The statement that Genes are found on chromosomes is true for almost all genes.
The cell organelles known as mitochondria contain a small number of genes within
their membrane boundaries. These genes are known as mitochondrial genes to
distinguish them from the chromosomal genes (located on chromosomes).
ODD FACT
In plants, a few
genes occur in the chloroplasts
that form part of the cytoplasm.
An estimated 20 000 to 25 000 human genes exist.
Genes are identied in terms of the functions they control.
A system of symbols to denote genes exists.
Excluding mitochondrial genes, genes are located on chromosomes in
the nucleus of eukaryotic cells.
Each gene occupies a specic position or locus on a chromosome.
Genes located on the same chromosome form a linkage group.
A very small number of genes exist in mitochondria.
KEY IDEAS
12 Identify the following as true or false:
a The locus of the gene for factor XII deciency is on chromosome 5.
b The HD gene is part of the same linkage group as the ACH gene.
c The DMD gene is located on the long arm of the X chromosome.
d The number of human genes is estimated to be in the range of
20 000 to 25 000.
13 Have all human genes been identied and named?
14 Where would you nd the locus of the gene controlling Rhesus blood
type?
15 Refer to table 9.5. Which of the following genes are part of the same
linkage group: ABO, AMY1, CF, RH, DMD?
16 Why are colour blind females far less common than colour blind males?
QUICK-CHECK
Alleles: particular forms of a gene
A gene that controls one function can exist in different forms or variants that are
called alleles of that gene. One gene can have several alleles and each is identi-
ed in terms of its specic action. The ABO gene that controls human ABO
blood type has three different alleles. Alleles of one gene are commonly repre-
sented by variations of one letter of the alphabet (see table 9.7).
How many alleles?
In terms of the phenotypic expression of genes, the common situation for most
genes is that they have two alleles as indicated in table 9.7. This is not always
the case, as can be seen for the ABO gene which has three common alleles, I
A
,
I
B
and i. When three or more alleles exist for a gene, the gene is said to have
multiple alleles. Table 9.8 (page 311) shows some examples of multiple alleles.
We will see later (chapter 12, page 439) that some chromosomal regions,
known as short tandem repeats (STRs), are hypervariable and each has multiple
alleles, ranging from 10 to 40 different alleles for the various STRs.
In this book, allele symbols are
shown in boldface italics.
Table 9.7
Gene and its function
Chromosomal
location Common alleles
ABO controls ABO blood type 9 I
A

I
B

i
produce antigen A
produce antigen B
produce neither antigen
CFTR controls type of secretion 7 C
c
normal secretions
abnormal secretions (cystic brosis)
CBD controls colour vision X V
v
produce green sensitive pigment
lack pigment (colour vision defect)
DMD controls muscle protein (dystrophin) X M
m
produce normal muscle protein
produce abnormal muscle protein
EL1 controls shape of red blood cells 1 E
e
elliptical red blood cells
usual shape
F8C controls blood clotting X H
h
produce factor VIII
no factor VIII (haemophilia)
HBB controls beta chains of haemoglobin 11 T
t
produce beta chains
beta chains missing (thalassaemia)
LDLR controls blood cholesterol level 19 B
b
abnormally high cholesterol level
normal range
PKU1 controls phe hydroxylase enzyme 12 P
p
produce normal enzyme
enzyme absent (PKU)
RH controls Rhesus blood type 1 D
d
Rhesus positive
Rhesus negative
TYR controls pigment production 11 A
a
produce tyrosinase enzyme
no enzyme (albinism) (see gure 9.29)
Figure 9.29 An albino woman and her dark-skinned sister
Gene function Multiple alleles and their action
controls human
ABO blood type
I
A
I
B
i
antigen A present
antigen B present
neither antigen present
controls white
spotting in dogs
S
s
i
s
p
s
e
white spots absent
Irish spotting (as in collies) (see gure 9.30b)
piebald spotting (as in fox terriers) (see gure 9.30a)
produce extreme spotting (as in Samoyeds or
Maltese terriers)
controls pigment
levels in cats
C
c
b
c
s
intense pigment (as in a black cat, see gure 9.31b)
Burmese dilution (see gure 9.31a)
Siamese dilution (see gure 9.31c)
controls colour
intensity in rabbits
C
c
ch
c
h
c
intense pigment (as in solid black)
Chinchilla colouring (white fur with black tips)
Himalayan colouring (colour on ears, nose, feet
and tail only)
albino (white fur and pink eyes)
controls white
markings in cattle
S
s
h
s
c
s
white band around middle (as in Galloways)
Hereford type spotting
solid colour with no spots (as in Belmont Reds)
Friesian type spotting
controls eye colour
in fruit-y
(Drosophila sp.)
w
+
w
a
w
h
w
p
w
i
w
red eye
apricot
honey
pearl
ivory
white
(c)
Figure 9.30 Dogs showing
(a) piebald spotting phenotype and
(b) Irish spotting phenotype
Figure 9.31 Cats showing
(a) Burmese dilution in which the
black pigment is reduced to brown,
(b) intense black pigment, and
(c) Siamese pigment in which the
pigment is further reduced and
restricted to the ears, face, feet and
tail. The order of dominance is
C > c
b
= c
s
.
(a)
(a)
(b)
(b)
Table 9.8 Multiple alleles of selected genes in various organisms. Not every allele
is shown in each case for example, there are more than 12 multiple alleles for the
Drosophila eye colour gene in this table.
Identifying genotypes
Genotypes for autosomal genes
Both females and males have two copies of each gene located on an autosome.
While people share identical genes, they may differ in the specic alleles they
possess.
Each person has two copies of the ABO gene on their pair of number-9
chromosomes. However, people may have different alleles of that gene. One
person may have two copies of the i allele, another person may have one copy of
the I
A
allele and one copy of the i allele, yet another person may have one copy
of the I
B
allele and one copy of the i allele. The particular combination of alleles
of a gene is that persons genotype in terms of that gene.
A person with two identical alleles such as genotype I
A
I
A
is said to be
homozygous. The gametes produced by that person will be identical, with all
having the same allele.
A person with two different alleles such as genotype I
A
I
B
is said to be
heterozygous. The gametes produced by that person will be of two kinds, with
half having the I
B
allele, and half having the I
A
allele.
Figure 9.32
ODD FACT
In AD 200,
a Jewish edict exempted from
circumcision a son if two
brothers had bled to death. Male
cousins were also exempted.
More of one sex: nding explanations
People have been aware for a long time that some conditions, such as certain
colour vision defects and a blood-clotting disorder (haemophilia) that occur in
particular families, appear more often in males than in females. Why?
This is because the genes controlling colour vision and blood clotting are
located on the X chromosome and are not represented on the Y chromosome. To
be affected, females must inherit two copies of the particular allele; males are
affected if they have just one allele so males more commonly show the trait.
When a gene is located on a sex chromosome, the traits controlled by its
alleles do not appear equally in both sexes.
Genes on the X chromosome
Many genes are located on the human X chromosome; such genes are said to
be X-linked. Examples of X-linked genes include the DMD gene, located on
the short arm of the X chromosome (refer back to gure 9.27, page 307). This
gene controls production of the muscle protein, dystrophin, that is found on the
membrane of voluntary muscle cells. The DMD gene has two alleles. When only
abnormal dystrophin is produced by muscle cells, a disorder called Duchenne
muscular dystrophy results. This disorder is extremely rare in females, but affects
about 1 in every 3500 male babies. Affected males suffer slow but irreversible
loss of the muscle function and are conned to a wheelchair usually before
they reach their teens (see gure 9.33). Death usually occurs before or in early
adulthood.
Males have only one X chromosome and so have one allele of this gene. A male
has a hemizygous genotype, and is either M or m. (These genotypes are shown as
M (Y) and m (Y), where the (Y) denotes the Y chromosome.) Males affected by
Duchenne muscular dystrophy have the hemizygous genotype m (Y).
Normal females with two X chromosomes have two alleles of the DMD gene.
A female with the heterozygous Mm genotype is not affected by muscular dys-
trophy, nor is a female with a genotype MM. Affected males invariably inherit
the m allele from a heterozygous mother, not an affected father. (Why?)
Y-linked genes
Compared with other chromosomes, the human Y chromosome carries a small
number of genes, including the SRY gene that controls production of a protein
that causes testes formation in a human embryo normally at about six weeks of
Figure 9.33 Children with
muscular dystrophy take part in
play group therapy.
embryonic development. If this protein is not produced, the gonads differen-
tiate to form ovaries. So this is the male-determining gene (with the letters SRY
coming from the Sex-determing Region of Y).
The SRY gene is said to be Y-linked. Normal males have one copy of each
Y-linked gene and so are hemizygous for Y-linked genes. Normal females have
no Y chromosome.
X-inactivation
We have seen that a normal male has only one copy of each gene that is X-linked
and so has a hemizygous genotype for all these genes. In contrast, normal females
have two copies of each X-linked gene and so can have either a homozygous or
a heterozygous genotype.
A British geneticist, Mary Lyon (1925 ), hypothesised that in normal female
mammals one of the two X chromosomes was randomly switched off in every
somatic cell so that only one X chromosome was active. What evidence exists to
support this hypothesis? Look no further than the tortoiseshell domestic cat (see
the box opposite).
Relationship between
expression of alleles
If you are simultaneously given two instructions that are mutually exclusive,
such as: Turn left at the next corner! and Turn right at the next corner!, you
can carry out only one instruction. However, for two other instructions, such
as: Paint the door yellow and Paint the door green, you might carry out both
instructions by producing a bi-coloured yellow and green door. Similar situations
can be recognised for the phenotypes produced by genes.
Complete dominance
Tracey and Johns baby, Fiona, was diagnosed as having albinism. The TYR
gene, located on the number-11 chromosome, has two alleles denoted A and a
(see table 9.7, page 310).
A person with the heterozygous Aa genotype has two mutually exclusive
genetic instructions, but such persons have skin and hair pigmentation. The
pigmented phenotype is dominant to albinism. Or, we can say that albinism is
recessive. Table 9.9 shows the relationship between genotypes and phenotypes
for the alleles of the TYR gene.
Table 9.9
Genotype Phenotype
homozygous AA pigment produced
heterozygous Aa pigment produced
homozygous aa no pigment (albinism)
To decide whether a trait is dominant or recessive, the phenotype of a hetero-
zygous organism is identied. The trait that is expressed in this phenotype is the
dominant trait.
Alleles that control dominant traits are usually symbolised by a capital letter;
for example, the allele S controls the dominant short fur length trait in cats.
Alleles that control recessive traits are symbolised by the lower case of the same
letter; for example, the allele s controls the recessive long fur length in cats.
ODD FACT
A common
misunderstanding is that
dominant traits are the common
traits. An inherited trait may be
common, but this observation
by itself does not justify the
conclusion that it is dominant.
In many cases, dominant
traits are rare, such as
Huntington disease.
In hunans, Lhere
are nore Lhan 1000 X-linked
genes, buL only 78 Y-linked
genes have so ar been
idenLiFed as aL January 2006.
TORTOISESHELL CATS AND THE X CHROMOSOME
Figure 9.35 Karyotype of a normal male cat. In addition to the 18 pairs of autosomes, this cat has one
X chromosome and one Y chromosome.
Cat breeders know that tortoiseshell colouring
orange (ginger) in combination with another colour,
usually black is almost always seen in cats that are
female (see gure 9.34). Breeders condently predict
that a black and orange tortoiseshell kitten would be
female.
Explaining the tortoiseshellfemale link
In cats, the gene that controls orange colouring is located
on the X chromosome. This gene has two alleles:
O
o
produce orange colouring
O
+
produce non-orange colouring.
The non-orange colour is controlled by other genes,
and is most commonly black. We will assume this to
be the case.
Cats have 38 chromosomes consisting of 18 pairs of
autosomes and one pair of sex chromosomes (see gure
9.35). Female cats have two X chromosomes and so have
two alleles of the gene controlling orange colouring.
Possible genotypes and phenotypes for female cats
are:
O
o
O
o
orange
O
o
O
+
orange and black (tortoiseshell)
O
+
O
+
black.
The orange-and-black phenotype of a female cat
with the heterozygous genotype is due to the fact that
in somatic cells, one only of the two X chromosomes
determines phenotype; the other X chromosome is appar-
ently switched off. Alleles of genes carried on that
X chromosome are not expressed. This process of
switching off or X-inactivation occurs during early
embryonic development and randomly affects one of the
X chromosomes in somatic cells. In hair cells in some
regions, only the X chromosome with the O
o
allele is
active and orange colour results. In hair cells in other
regions, only the X chromosome with the O
+
allele is
active and non-orange colour, usually black, results.
Figure 9.35 shows the karyotype of a normal male
cat.
Normal male cats have one X chromosome and one
Y chromosome. Possible hemizygous genotypes for
males are:
O
o
(Y) orange
O
+
(Y) black.
Male tortoiseshell cats are occasionally identied
and are often found to have 39 chromosomes, instead
of the usual 38. Can you predict the identity of the extra
chromosome? These cats have an extra X chromosome.
Can you explain how they can show the phenotypic
effect of both an O
o
allele and an O
+
allele?
Grey and cream colouring is diluted black and
orange. Almost without exception, grey and cream cats
are female, not male. Is this unexpected?
Figure 9.34 Two tortoiseshell (tortie) females showing their
orange and black colouring
If the genotype of an individual
is unknown but could be either
Aa or AA, this may be denoted
as A (where represents
either allele).
As well as co-dominance,
you may see terms such as
partial dominance or incomplete
dominance in various
genetics books.
Being a carrier
In genetics, the term carrier refers to a heterozygote that has the allele for a reces-
sive trait but does not show the trait. In people, alleles may be carried for hidden
recessive traits that do not affect normal functioning, such as straight hairline and
blood type O. However, some alleles that are carried by heterozygotes are for
recessive disorders, such as cystic brosis or albinism (see table 9.10).
Table 9.10 Some dominant and recessive human traits. Heterozygotes carry alleles
for recessive traits but their effects are not expressed. What genotype is necessary for a
recessive trait to be expressed for an autosomal gene?
Dominant trait Recessive trait
peaked hairline (widows peak) (W) straight hairline (w)
free ear lobes (F) attached ear lobes (f)
mid-digital hair present (G) mid-digital hair absent (g)
shortened ngers (brachydactyly) (S) normal length ngers (s)
normal pigmentation (A) pigmentation lacking (albinism) (a)
non-red hair (R) red hair (r)
normal secretions (C) cystic brosis (c)
dwarf stature (achondroplasia) (N) average stature (n)
Rhesus positive (Rh +ve) blood (D) Rhesus negative (Rh ve) blood (d)
Most often, heterozygotes are not aware of their carrier status for an allele
controlling a recessive trait. Parents may realise they are carriers only when they
have a baby with a recessive disease. Tracey and John, the parents of the albino
baby, Fiona, were unaware that they were each genotype Aa and so were carriers
of an allele that resulted in lack of pigment production until baby Fiona was
born.
People with heterozygous genotypes sometimes know that they are carrying
a hidden allele. Consider the case of Maria, a young woman living in a suburb
of Melbourne. Both Marias sister and her cousin have thalassaemia, a recessive
inherited disorder affecting the haemoglobin in red blood cells. Maria wondered
if she was a carrier. A simple test done through the Thalassaemia Society in
Melbourne conrmed that Maria was a carrier of thalassaemia with the hetero-
zygous genotype Tt.
Co-dominance
The ABO gene, located on the number-9 chromosome, has three alleles that
determine antigen production (see table 9.7, page 310).
Antigen A and antigen B occur on the surface of the red blood cells of some
people. Depending on which antigens are present, blood is typed as group A, B,
AB or O. The presence (or absence) of a particular antigen is inferred by adding
specic antibodies and observing the result (see gure 9.37). Antibodies used
to type blood are anti-A antibodies and anti-B antibodies. Anti-A antibodies
cause clumping or agglutination of red blood cells with antigen A. Anti-B anti-
bodies cause clumping of red blood cells with antigen B.
Figure 9.36 A short-statured man
at work. Achondroplasia is due to the
action of one allele at the ACH gene
locus, with dwarsm being dominant
to normal stature. While aspects of
their skeletal structure are affected,
people of short stature (which is
their preferred description) are
otherwise unaffected and play normal
roles in society.
Look at the reaction of the blood sample from Tran (column 3). His blood
clumped when anti-A antibodies were added, so his red blood cells have antigen
A and he has the allele I
A
. Trans blood also clumped when anti-B antibodies
were added, so his red blood cells have antigen B and he must also have the allele
I
B
. Trans genotype is heterozygous I
A
I
B
. Because both traits are expressed in
the heterozygote, these two alleles show co-dominance. Alleles showing co-
dominance are denoted by a capital letter with a superscript added to distinguish
between them. Table 9.11 shows that the phenotypic actions of both the I
A
and I
B

alleles are dominant to the action of the i allele, and so blood group O is recessive
to the other blood types.
Genotype
Instructons carried
by alleles Phenotype
homozygous I
A
I
A
produce antigen A blood type A
homozygous I
B
I
B
produce antigen B blood type B
homozygous ii produce neither antigen A nor B blood type O
heterozygous I
A
I
B
produce antigen A and produce
antigen B
blood type AB
heterozygous I
A
i produce antigen A and produce
neither antigen
blood type A
heterozygous I
B
i produce antigen B and produce
neither antigen
blood type B
Genes and alleles in domestic mammals
Like people, plants and other animals carry genetic instructions or genes on
their chromosomes. Figure 9.38 identies some phenotypes due to the action
of common alleles in several domestic mammals: cat (Felis catus), dog (Canis
familiaris) and horse (Caballus equus).
Figure 9.37 Addition of specic
antibodies to blood samples causes
cells to clump or agglutinate when
the corresponding antigen is present
on the surface of the red blood cells.
Table 9.11 Relationship between
genotypes and phenotypes for the
ABO gene. What relationship exists
between the I
A
and the I
B
alleles?
Between the I
B
and the i alleles?
1 2 3 4 5
ANTI-A
ANTI-B
ANTI-A
+
ANTI-B
Figure 9.38 Some
phenotypes in domestic
mammals and their possible
genotypes. Which is dominant
in cats: dense colour (black)
or dilute colour (grey)? What
is the action of the
G allele in horses?
Black Black Chestnut
Grey Brown Bay
Black tabby Red Grey
aa BB DD BB EE AA bb gg
aa BB dd bb EE AA BB gg
AA BB DD ee GG
Environmental interactions with
genotypes
The phenotypes shown in gure 9.38 are true expressions of the underlying geno-
types. However, a phenotype is not always produced exclusively by the genotype.
In some cases, the phenotype is a result of the interaction of the genotype and
environmental factors:
genotype + environment phenotype
Many environmental factors, both external and internal, act on an organism
so that its nal phenotype is due to varying contributions of genotype and
environment.
The phenotype due to a particular genotype may appear only in one specic
environment. In a different environment, another phenotype may appear. Lets
examine some examples of how environmental factors can affect the phenotype.
ODD FACT
For a fetus, its
environment is the mothers
uterus. A mothers actions
drinking alcohol, smoking
can change this environment
and affect the phenotype
of the fetus.
PKU and dietary-controlled phenotype
The inherited disorder, phenylketonuria (PKU) results from the action of the
gene that controls production of an enzyme known as phe hydroxylase. Babies
that inherit the homozygous recessive genotype pp from their parents cannot
produce this enzyme. If these babies are fed diets that include proteins that
contain normal quantities of the amino acid, phe, the babies will suffer brain
damage and become mentally retarded, so early diagnosis is critical (see the
newborn screening card in gure 9.39). However, if these babies are fed a special
diet that includes proteins with very low levels of phe, the babies will not suffer
brain damage and will show a normal phenotype.
In this case, the phenotype of a child with genotype pp depends on the internal
environment that is controlled by the diet:
genotype pp + HIGH phe level in diet phenotype: PKU with
mental retardation
genotype pp + LOW phe level in diet phenotype: normal
Figure 9.39 Special blotting
paper with a sample of blood taken
from a baby a few days after birth.
Small discs of blood-soaked paper
are tested for the presence of
phenylalanine (phe). A high level of
phe indicates that the baby has PKU.
As we saw in chapter 4 (see pages 1034), Phe is present in high levels in
proteins such as red meat, chicken, sh, lentils, dairy products, eggs, wheat and
other grains. Phe is present at lower levels in most fruit and vegetables. Foods
such as sugar, honey, jam, low protein pasta, jellies, and special breads made
from PKU bread mix contain no phe. A child with the missing enzyme cannot
have a diet that has no phe, because this is an essential amino acid required for
growth and development. Early diagnosis is vital and can be achieved only by
screening. The child must have an intake of phe, but not too much because the
body will not be able to dispose of the excess. The diet of such a child must be
critically balanced. The child needs to take a protein supplement which consists
of all the essential amino acids except phe.
Cats and temperature
Figure 9.40a shows some Siamese kittens. At birth, these kittens are all white.
A few weeks later, the kittens begin to develop pigmentation rst along the edges
of their ears. Gradually the pigment spreads until the kittens show the character-
istic colouring on the face, ears, feet and tail. This pattern of colour change is due
to an interaction between the cats genotypes and their environment.
Refer back to chapter 4, pages
1025, to read more about PKU.
Cooler
Cooler
Warmer
Figure 9.40 (a) Red point and
seal point Siamese kittens. What
colour were they at birth?
(b) How does the environment
affect their colouring?
(a)
(b)
One gene can exist in a number of different forms, called alleles.
Each different allele is identied by its specic phenotypic action.
A person is said to be homozygous when she/he has two identical
alleles and heterozygous when she/he has two different alleles of one
gene.
Males are hemizygous for both X-linked and Y-linked genes.
When an allele is expressed in the phenotype of a heterozygote
organism, the trait controlled by that allele is dominant.
The trait controlled by the hidden allele in a heterozygote is
recessive.
When two different alleles are both expressed in the phenotype of a
heterozygous organism, they are said to show co-dominance.
The phenotype of an organism can be due to an interaction between
the genotype and the environment.
KEY IDEAS
Siamese cats have a particular form of a gene that is involved in the pigment
production. This gene codes for the production of tyrosinase. This enzyme
catalyses one step in the production of pigment:
tyrosinase
precursor pigment
In Siamese cats, the particular form (allele) of this gene produces a tyro-
sinase enzyme that is heat-sensitive. This enzyme can catalyse the step in the
production of pigment only when the temperature is lower than the core body
temperature. Siamese kittens undergo embryonic development in a warm uterine
environment and so are born unpigmented (white). Pigment appears rst on the
coolest parts of their bodies the ear margins and then on other extremities
(gure 9.40b).
Plants and soil pH
Hydrangea plants (see gure 9.41) produce blooms with colours that vary
depending on the acidity or alkalinity (pH) of the soil in which they are growing.
The colour is due to pigments known as anthocyanins which are located in
membrane-bound sacs within the petal cells. In soil with an acidic pH, these
pigments are a bright blue, while at alkaline pH, they are a pale pink or
off-white.
Figure 9.41 Hydrangeas.
When grown in acid soil, hydrangeas
produce deep blue owers. In
contrast, when grown in non-acid
soil, the ower colour is pink or
off-white. Is variation in ower
colour in hydrangeas under genetic
or environmental control?
Rules of the genetic game
What kinds of children?
Tracey and John are planning their next pregnancy. One of their rst-born non-
identical twin children, Fiona, has the condition of albinism and the parents
want to know about the chance of this condition appearing in their next child.
Figure 9.42 shows the chromosomal portraits of Tracey, John and their twins.
Both parents are carriers of albinism and have the genotype Aa. In terms of their
ABO blood types, both parents are blood group B, while the twins are both blood
group O. It may be concluded that both parents have the genotype I
B
i. (Why?)
Figure 9.42 Genotypes and
phenotypes of Tracey, John, Fiona
and Tim. What is the chance that
Tracey and Johns next baby could
show albinism? What is the chance
that it too will be blood group O
like its siblings?
17 Fill in the following gaps with the term gene or allele:
a the _____ that produces short fur length in cats
b the _____ controlling fur length in cats.
18 Explain the difference between the members of the following pairs of
terms:
a homozygous and heterozygous
b X-linked and Y-linked.
19 Refer to table 9.7 on page 310. What is the phenotype and sex of a
person with the genotype I
B
I
B
, MM?
20 Natalie displays the dominant peaked hairline but her mother shows
the recessive straight hairline.
a What is Natalies genotype?
b What is her mothers genotype?
21 The offspring of a homozygous purple and a homozygous pink plant are
bi-coloured purple and pink.
a Assuming that a single gene is involved, what relationship exists
between the phenotypic expression of alleles?
b Would your conclusion change if the offspring were purple? Explain.
QUICK-CHECK
The alleles that parents pass on to their children are determined by the chromo-
somal sorting that occurs during gamete formation by meiosis. Non-homologous
chromosomes behave independently of each other during meiosis.
I
B
i
I
B
i A a I
B
i A a i

i
Tim Fiona John Tracey
a a i

i A A
9
Group B
Normal pigment
Genotype
Chromosomes
Phenotype
Group B
Normal pigment
Group O
Albino
Group O
Normal pigment
9 11 11
A a
I
B
i
9 9 11 11
A a
i i
9 9 11 11
a a
i i
9 9 11 11
A A
Traceys eggs
J
o
h
n
s

s
p
e
r
m
1
4
A
1
2
A
1
2
a
1
2
a
1
2
Normal
AA
3
4
normal :
1
4
albino
1
4
AA :
2
4
Aa :
1
4
aa
1
4
Normal
Aa
1
4
Normal
Aa
1
4
Albino
aa
First look at the number-11 chromosomes
For the TYR gene on the number-11
chromosome, which controls pigment
production, the cross can be shown as
at right.
During meiosis, the pair of
number-11 chromo somes disjoin
carrying the alleles to different
gametes. Traceys eggs have either the A allele or the a allele. This also applies
to the sperm cells produced by John. This separation of the alleles of one gene
into different gametes that occurs during meiosis is known as the segregation of
alleles. For each parent, the chance of a gamete with A is 1 in 2, and the chance
of a gamete with a is also 1 in 2.
These probabilities can also be incorporated into a Punnett square (gure 9.43).
Tracey
A a
John
A a
x
ODD FACT
The chance of an
event can be expressed as a
fraction (say, 1/4), a percentage
(25%), a ratio (1 in 4) or a
decimal (0.25). When a decimal
number is used, the value
0 represents an impossible
occurrence and a chance of 1
represents a certainty.
So, the chance that you will
run a two-minute mile today is
0 and the chance that you will
take a breath in the next
half hour is 1.
The AA and the Aa genotypes both result in normal pigmentation. The aa
geno type causes albinism.
A Punnett square shows the chance of each possible outcome, not what
will happen. This Punnett square simply shows that the chance of a child with
normal pigmentation from this cross is 3/4 and the chance of a child with
albinism is 1/4.
Now look at the number-9 chromosomes
For the ABO gene on the number-9
chromosome, which controls the
ABO blood types, the cross is shown
at right.
Disjunction of the number-9
chromosomes during meiosis in
Tracey means that her eggs will have
either one I
B
allele or one i allele and
the chance of each type is 1/2. Johns number-9 chromosomes also disjoin during
meiosis. Likewise, his sperm cells will have either one I
B
allele or a i allele.
The chance of a child with blood group B is is 3/4. The chance of a child with
blood group O is 1/4. Can you construct a Punnett square to show this?
ODD FACT
When alleles of
one gene only are involved, a
cross is said to be monohybrid.
When alleles of two gene loci
are involved, a cross is said to
be dihybrid. What do you think
is involved in a trihybrid cross?
Tracey
I
B
i I
B
i
John
x
I
B
i I
B
i
Figure 9.43
Figure 9.45 Punnett square
showing the cross of Tracey and
John. Note that, in the overall
summary statement below the
Punnett square, the dash symbol
() means that the second allele in
the genotype can be either of the
two possible alleles. So, for example,
A denotes both AA and Aa.
iiAa
1
16
iiAA
1
16
iiAa
1
16
I
B
i Aa I
B
i Aa
Tracey John
IA
1
4
IA
1
4
Ia
1
4
iA
1
4
ia
1
4
Ia
1
4
iA
1
4
ia
1
4
IIAA
1
16
IIAa
1
2
IIAa
1
16
IIaa
1
16
IiAA
1
16
IiAa
1
16
IiAa
1
16
Iiaa
1
16
IiAA
1
16
IiAa
1
16
IiAa
1
16
Iiaa
1
16
iiaa
1
16
Overall
summary
I
B
A
9
16
: I
B
aa
3
16
: iiA
3
16
: iiaa
1
16
Group B
normal
pigment
9 Group B
albino
3 Group O
normal
pigment
3 Group O
albino
1
Traceys eggs
J
o
h
n
s

s
p
e
r
m
x
Combining probabilities
Consider tossing two dice. What is the chance of throwing double 6? The outcomes
for the two dice are independent events and the chance of the combined events
is found by multiplying the chance of each separate event. The chance of a six
with the rst die is 1/6. The chance with the second die is 1/6. So, the chance of
a double 6 is 1/6 1/6 = 1/36.
The disjoining of one pair of chromosomes is independent of the disjoining of
the other pairs. This independent disjoining juggles the gene combinations in
a process termed gene assortment. The chance that Tracey and John will have a
child that has albinism is 1/4 and the chance that the child will have blood type O
is 1/4. These are independent events so the combined chance of a child that has
albinism and has O blood type is 1/4 1/4 = 1/16. The chance that the next child
will be blood group B and have normal pigmentation is 3/4 3/4 = 9/16. What is
the chance of a child with blood group B and albinism?
A dihybrid cross AaIi AaIi can be considered as a combination of two mono-
hybrid crosses (see gure 9.44) or seen as a Punnett square (see gure 9.45).
Figure 9.44 Looking at a
dihybrid cross. What is the chance
of a aaII offspring? Note that, for
convenience, the B superscript has
been omitted from symbols inside
the square, but you should remember
that, where the I appears, it is the
I
B
allele.
Aa x Aa Ii x Ii AAII : 1/4 x 1/4 = 1/16
Locus 1 Locus 2 Offspring and chance
Aaii : 1/2 x 1/4 = 1/8
1/4 AA : 1/2 Aa : 1/4 aa 1/4 II : 1/2 Ii : 1/4 ii AaIi : 1/2 x 1/2 = 1/4
aaii : 1/4 x 1/4 = 1/16
etc.
Dad Mum
It took me to
show that black dad
is heterozygous
Dd.
Sarah has elliptical red blood
cells and is Rhesus positive; her
genotype is Dd Ee. Dave has normal
red blood cells and he is Rhesus
negative; his genotype is dd ee.
Consider the cross between Sarah
and Dave at right.
The gure shows the arrange-
ments of the alleles of the two genes
on the chromosomes in Sarah and David. Their genotypes can be written as
DE/de and de/de respectively. Because the RH and the EL1 genes are physically
close together on the number-1 chromosome, alleles of these two genes do not
behave independently, as is the case for the TYR and the ABO genes.
Test crosses
A cross involving a single gene, such as Aa Aa, is termed a monohybrid cross,
while a cross involving two genes, such as AaBb AaBb, is called a dihybrid
cross.
Another important type of cross that can be either monohybrid or dihybrid is
a test cross. A test cross involves one parent that is homozygous recessive, such
as aa or aabb, and is used for the following purposes:
to identify if an organism showing a dominant trait is homozygous or
heterozygous
to establish linkage relationships between genes.
In reality, today, it is possible to make these decisions using molecular
techniques.
Lets look at how a test cross was able to identify whether an organism showing
a dominant phenotype was homozygous or heterozygous.
In cats, one gene controlling coat colour has the alleles intense and dilute,
with intense colour, such as black (D), being dominant to dilute colour, such as
grey (d). A black cat of unknown parentage may have the genotype
either DD or Dd. A cross of this cat with a grey cat will, if the
black cat is homozygous dominant DD, produce only black
kittens. Why? If the black cat is heterozygous Dd, the cross
with a grey cat can produce black kittens and grey kittens with
an equal chance of either colour. Can you prepare a Punnett
square showing one of these crosses? While only one grey
kitten is needed to identify that the black cat must be hetero-
zygous Dd (see gure 9.46) a minimum of 16 successive
black offspring is required before it can be concluded with
reasonable condence that the black cat is homozygous
dominant DD.
Linked genes can also be denoted
in other ways when the allele
arrangements are known.
For example:
A b
OR Ab/aB OR
A b
a B a B
Figure 9.46
Sarah
D
E
d
e
x
Dave
d
e
d
e
What about
linked genes?
The RH gene that controls Rhesus blood
type and the EL1 gene that controls the
shape of red blood cells are close together
on the number-1 chromosome and so are
said to be linked.
Because the loci of two linked genes are physically close, the particular
combi nation of alleles of the genes that are present on parental chromosomes
will tend to be inherited together more often than alternative combinations. These
combinations of alleles can, however, be broken by crossing over during meiosis
so that new combinations of alleles are generated. The chance that this will occur
depends on the distance between the two linked genes (see gure 9.47).
Sarah can produce both DE eggs and de eggs and the chance of each type is
equal. These eggs are called parental or non-crossover eggs because they are
identical with the original allele combinations present in Sarah. Crossing over
and an exchange of segments can occur anywhere along the paired number-1
chromosomes. When an exchange occurs between the RH locus and the EL1
locus, recombinant or crossover eggs result. Sarahs recombinant eggs are De
and dE.
Crossing over occurs between all paired chromosomes during meiosis.
A crossover point is more likely to occur between two genes that are widely
separ ated on a chromosome than between two gene loci that are closer together.
The closer the genes, the smaller the chance of a crossover. Because the loci of
the RH gene and the EL1 gene are very close on the number-1 chromosome,
the chance of a crossover occurring between them is small. As a result, Sarahs
eggs are more likely to transmit the parental rather than recombinant types. We
will assume that for these two genes the chance of each kind of parental (non-
crossover) gamete is 0.49 and the chance of each type of recombinant gamete is
0.01.
Since Dave is homozygous, he produces only de sperm cells a 1.0 chance.
A Punnett square can be drawn up to show the chance of production of each
kind of gamete, and the chance of each possible offspring (gure 9.48).
Figure 9.47 Alleles of closely
linked genes are more likely to be
inherited together than the alleles
of widely separated genes. Why?
During crossing over:
Figure 9.48
Sarahs eggs
D
E
d
e
D
e
d
E
D
a
v
e
s

s
p
e
r
m
d
e
Rh+ve
elliptical
0.49 DE /de
Rhve
normal
0.49 de /de
Rh+ve
normal
0.01 De /de
Rhve
elliptical
0.01 dE /de
1.0
0.49 0.49 0.01 0.01
For Sarah and Dave, what is the chance of a child with Rh negative blood and
elliptical red blood cells? This phenotype corresponds to the genotype dE/de.
The chance of this offspring is 0.01 or 1/100.
Detecting linkage
Are two gene loci linked? This question may be explored by looking at the results
of a particular test cross of a known double heterozygote (Aa Bb) with a double
homozygous recessive (aa bb). If the two gene loci are not linked, the genes will
assort independently and the outcome of the test cross will be four classes of
offspring in equal proportions (see gure 9.49).
If the two gene loci are linked, the outcome of the test cross can reveal that
linkage. There will be four classes of offspring but the proportions of these will
not be equal. Instead, there will be an excess of offspring from parental gametes
and a deciency of offspring from recombinant gametes.
Linked gene loci are located close
together on the same chromosome
(separated by a distance of no
more than 40 map units) and do
not assort independently.
Figure 9.49
Parent 1
Because of equal numbers of each kind of offspring, we can conclude that the genes
are not linked but are assorting independently and the chromosome make-up of
the cross is:
A a
B
AaBb
b
ab
AB ab Ab aB
25% 25% 25% 25%
AaBb aabb Aabb
AaBb aabb
aaBb Offspring
Ratio
Parent 1 gametes
P
a
r
e
n
t

2
g
a
m
e
t
e
s
x
x
Parent 2
a a
b
aabb
b
ESTIMATING DISTANCE BETWEEN LINKED GENES
Figure 9.50
From the results of a test cross with linked genes, it
is possible to estimate the distance between the gene
loci. This estimate is based on the percentage of
recombinant offspring.
Distance between loci =
100 number of recombinant offspring
total number of offspring
The percentage of recom-
binant offspring corresponds
to the number of map units
separating the two genes. So,
if there are 12 per cent total
recombinant offspring, then
the loci of the two genes are
separated by about 12 map
units (see gure 9.50).
.
Parent 1
Because of unequal numbers of parental and recombinant offspring, we can conclude
that the genes are linked, the genotypes can be written as shown in the table and the
chromosome make-up of the cross is:
E e
EF /ef
12 map units
ef
EF ef Ef eF
44% 44% 6% 6%
EF /ef ef /ef Ef /ef
EeFf eeff
eF /ef Offspring
Ratio
Parent 1 gametes
Parental type Recombinant type
P
a
r
e
n
t

2
g
a
m
e
t
e
s
x
x
Parent 2
e e
F f f f
ef /ef
Predicting outcomes of crosses for linked
genes
When a test cross is carried out with two genes that are known to be linked and
are separated by a known number of map units (but less than 40), the outcome
of the cross can be predicted. For example, if two linked genes are separated by,
say, 8 map units, then a test cross involving these genes will produce about 8 per
cent of the recombinant type offspring and about 92 per cent of the parental type
offspring. The actual genotypes and phenotypes of the recombinant offspring
will depend on which alleles of the two genes were together originally on the
one chromosome in the heterozygous parent, before any crossing over occurred
during gamete formation. For example, the test cross RT/rt rt/rt gives 8 per cent
recombinant offspring. The cross Rt/rT rt/rt also gives 8 per cent recombinant
offspring. However, the genotypes of the recombinant offspring differ in each
case as shown in gure 9.51.
Note that the outcome of a test cross involving two linked genes allows you
to deduce how the alleles of the genes are arranged on the chromosomes of the
heterozygous parent.
Figure 9.51
Female
R r
RT /rt
8 map units
46% 46% 4% 4%
RT /rt rt /rt rT /rt Rt /rt
46% 46% 4% 4%
Eggs of RT /rt parent
Offspring and their proportions
S
p
e
r
m

o
f

r
t

/
r
t

p
a
r
e
n
t
x
Male
r r
T t
r r
or
t t
R
T
r
t
r
T
R
t
t t
rt /rt
Female
R r
Rt /rT
8 map units
46% 46% 4% 4%
Rt /rt rT /rt rt /rt RT /rt
46% 46% 4% 4%
Eggs of Rt /rT parent
Offspring and their proportions
S
p
e
r
m

o
f

r
t

/
r
t

p
a
r
e
n
t
x
Male
r r
t T
r r
or
t t
R
t
r
T
r
t
R
T
t t
rt /rt
Family pedigrees: drawing
genetic portraits
A family portrait is an important record of events in the life of a particular family.
Photographs of groups of family members are commonly taken on occasions
such as a wedding, a 21st birthday party or a graduation. A different kind of
family picture can be made to show the inheritance of a particular trait. This kind
of picture is called a pedigree. In drawing a human pedigree certain symbols are
used (see gure 9.52).
The chance of various kinds of offspring from a cross can be identied
from knowledge of the kinds and proportions of gametes that parents
can produce.
The probability of two independent events is the product of their
separate probabilities.
When genes are linked, parental gametes will be produced and, in
addition, recombinant gametes will arise from crossing over.
The closer two linked genes are, the less the chance that crossing over
will separate them during meiosis.
The result of a test cross involving two genes can identify whether the
genes are linked or not.
When genes are closely linked and separated by a known map distance,
the results of a test cross can be predicted.
KEY IDEAS
Figure 9.52 A pedigree and explanation of symbols used
22 Assume that a gene on the number-6 chromosome has the alleles
A and a, and that a second gene on the number-8 chromosome has
the alleles B and b.
a What kinds of gametes could be produced by a person, genotype
Aa Bb?
b A person produces gametes of one type only, aB. What is the
probable genotype of this person?
23 A man has the genotype RT/rt and these two gene loci are linked.
Would he produce more Rt gametes than RT gametes? Explain.
24 What is the difference between parental and recombinant gametes?
QUICK-CHECK
I, II
I
II
III
Key to symbols
Normal female Carrier (heterozygote)
Non-identical twins
Identical twins
First, second, etc., generation
Normal male
Female with the trait
being investigated
Male with the trait
being investigated
Mating line
1 2
1 2
1 2 3 4 5 6
3 4
The pattern of inheritance of a trait in a pedigree may provide information
about the trait. The pattern may indicate whether:
the trait concerned is dominant or recessive
the controlling gene is located on an autosome or on a sex chromosome.
However, a single pedigree may not always provide conclusive evidence.
Autosomal dominant pattern
Figure 9.53 shows the pattern of appearance of familial hypercholesterolaemia
in a family. This is an inherited condition in which affected individuals have
abnormally high levels of cholesterol in their blood. Affected individuals are
at risk of suffering a heart attack in early adulthood. The gene concerned is the
LDLR gene located on the short arm of chromosome 19. Abnormally high blood
cholesterol level (B) is dominant to normal levels (b). So, hypercholesterolaemia
is expressed in a heterozygote.
Figure 9.53 Pedigree for highly
elevated blood cholesterol levels, an
autosomal dominant trait. Does every
affected person have at least one
affected parent?
Recall that 4p16 reads as
chromosome 4, short arm, major
region 1, sub region 6 (see caption
for gure 9.27, page 307).
Cleft palate can have several other
causes, besides a genetic cause.
An idealised pattern of inheritance of an autosomal dominant trait includes
the following features:
both males and females can be affected
all affected individuals have at least one affected parent
transmission can be from fathers to daughters and sons, or from mothers to
daughters and sons
once the trait disappears from a branch of the pedigree, it does not reappear
in a large sample, approximately equal numbers of each sex will be affected.
Other autosomal dominant traits include:
Huntington disease, a degenerative brain disorder; controlled by the HD gene
on the short arm of the number-4 chromosome (4p16)
achondroplasia, a form of dwarsm; controlled by the ACH gene on the short
arm of the number-4 chromosome (4p16)
familial form of Alzheimer disease; controlled by the AD1 gene on the long
arm of the number-21 chromosome (21q21)
defective enamel of the teeth; controlled by the DGI1 gene on the number-4
chromosome (4q13)
neurobromatosis, the Elephant man disease; controlled by the NF1 gene on
the number-17 chromosome (17q11)
familial breast cancer controlled by the BRCA1 gene on the number-17
chromosome (17q21)
lip pits and cleft palate; controlled by the LPS gene on the number-1
chromosome (1q32).
Autosomal recessive pattern
Figure 9.54 is a pedigree showing the pattern of inheritance of oculo-cutaneous
albinism, a condition in which pigmentation is absent from skin, eyes and hair.
Albinism (a) is an autosomal recessive trait.
I
II
III
IV
1 2
1 2 3 4 5
1 2 3
6 7
1 2 3
5 6 4
Figure 9.54 Pedigree for albinism,
an autosomal recessive condition.
Can a person show an albino
phenotype even though neither
parent has the condition?
I
II
III
IV
1 2
4 5
2 1 4 3
2 3 1
1 2
8 6 7
1 2 3
Figure 9.55 Simons red hair is an
example of an autosomal recessive
trait. Must his parents also have red
hair?
An idealised pattern of inheritance of an autosomal recessive trait includes the
following features:
both males and females can be affected
two unaffected parents can have an affected child
all the children of two persons with the condition must also show the
con dition
the trait may disappear from a branch of the pedigree, but reappear in later
generations
over a large number of pedigrees, there are approximately equal numbers of
affected females and males.
Other autosomal recessive traits include:
cystic brosis, controlled by the CFTR gene on the number-7 chromosome
(7q31)
thalassaemia, a blood disorder; controlled by the HBB gene on the number-11
chromosome (11p15)
Tay-Sachs disease, a degenerative disease of the central nervous system that
causes death in infancy and is common in Jewish people of middle-European
ancestry; controlled by the HEXA gene on the number-15 chromosome
(15q23)
Wilson disease, a disease in which copper metabolism is abnormal; controlled
by the WND gene on the number-13 chromosome (13q14)
insulin-dependent diabetes mellitus-1; controlled by the IDDM1 gene on the
number-6 chromosome (6p21)
phenylketonuria; controlled by the PKU1 gene on the number-12 chromosome
(12q24)
red hair colour (see gure 9.55), controlled by the HCL2 gene; located on the
number-4 chromosome (4q28)
a form of osteogenesis imperfecta (brittle bones), a disorder affecting the
collagen protein of bones; controlled by the COL1A1 gene on the number-17
chromosome (17q21)
galactosaemia, a disease in which a person cannot metabolise the major sugar
(galactose) found in milk; controlled by the GALT gene on the number-9
chromosome (9p13).
X-linked dominant pattern
Figure 9.56 shows a pedigree for one form of vitamin D-resistant rickets in a
family. This form of rickets is an X-linked dominant trait, controlled by the HYP
gene located on the X chromosome (Xp22) and is expressed even if a person has
just one copy of the allele responsible.
An idealised pattern of inheritance of an X-linked dominant trait includes the
following features:
a male with the trait passes it on to all his daughters and none of his sons
a female with the trait may pass it on to both her daughters and her sons
every affected person has at least one parent with the trait
if the trait disappears from a branch of the pedigree, it does not reappear
ODD FACT
In the past, babies
with cystic brosis (CF) were
detected when the midwife
licked the babys forehead.
A salty taste was a clue to CF.
over a large number of pedigrees, there are more affected females than males.
Other X-linked dominant traits include:
incontinentia pigmenti, a rare disorder that results in the death of affected
males before birth; controlled by the IP2 gene on the X chromosome (Xq28)
Xg(a) blood group; controlled by the XG gene on the X chromosome
(Xp22).
X-linked recessive pattern
Figure 9.57 shows the pattern of appearance of favism in a family. Favism is a
disorder in which the red blood cells are rapidly destroyed if the person with
this condition comes into contact with certain agents. These agents include sub-
stances in broad beans and mothballs.
Figure 9.56 Pedigree for
vitamin D resistant rickets, an
X-linked dominant condition. Look
at the daughters and sons of affected
males what pattern is apparent?
Could daughters of person III-3
show the trait?
I
II
III
IV
1 2
1 2 3 4
1 2
5 6
1 2
3 4
3 4
Figure 9.57 Pedigree for favism
an X-linked recessive disorder.
Can this disorder skip a generation?
I
II
III
IV
V
1 2
1 2
1 2 3
5 4 3
2 1
5 4 3 2 1
ODD FACT
People lacking the
G6PD enzyme are sensitive to
the drug primaquine which
is used in the treatment of
malaria. After a few days on
this drug, such people develop
jaundice and excrete very
dark, even black urine. These
symptoms are due to the
massive breakdown of
red blood cells.
Favism results from a missing enzyme and is controlled by the G6PD gene
on the long arm of the X chromosome (Xq28). Favism (f ), which occurs when
the G6PD enzyme is absent from red blood cells, is recessive to the unaffected
condition (F), which occurs when the enzyme is present. The condition of favism
is inherited as an X-linked recessive and is expressed only in females with the
homozygous (ff ) genotype or in males with the hemizygous (f ) (Y) genotype.
An idealised pattern of inheritance of an X-linked recessive trait includes the
following features:
all the sons of a female with the trait are affected
all the daughters of a male with the trait will be carriers of the trait and will not
show the trait; the trait can appear in their sons
none of the sons of a male with the trait and an unaffected female will show
the trait, unless the mother is a carrier
all children of two individuals with the trait will also show the trait
in a large sample, more males than females show the trait.
Other X-linked recessive traits include:
ichthyosis, an inherited skin disorder; controlled by the STS gene on the
X chromosome (Xp22)
one form of redgreen colour-blindness; controlled by the CBD gene on the
X chromosome (Xq28)
one form of severe combined immunodeciency disease; controlled by the
SCIDX gene on the X chromosome (Xq13)
haemophilia, an inherited blood-clotting disorder; controlled by the F8C gene
on the X chromosome (Xq28)
one form of mental retardation, known as fragile X syndrome; controlled by
the FMR1 gene on the X chromosome (Xq27)
Duchenne muscular dystrophy; controlled by the DMD gene on the X chromo-
some (Xp21).
In this chapter, we have examined conditions and disorders that are chromo-
somal or genic in origin. In the following box, you can read about the work of a
group at the Murdoch Childrens Research Institute who collect and analyse data
on various conditions.
As Head of the Public Health Genetics Unit at the
Murdoch Childrens Research Institute, I work along-
side medical geneticists and genetic counsellors who
look after children with inherited conditions and
counsel adults about the risk of passing on a genetic
disorder to their child. Inherited conditions such as
cystic brosis are caused by changes (mutations)
in specic genes, and the genetic counselling for such
conditions usually takes place in a hospital-based clinic
with members of the family. There is another group of
genetic conditions that are not inherited. These occur
because of errors in cell division that lead to an extra
chromosome in the fetus as is the case in Down
syndrome.
I was rst involved in data collection when there
were only a few hundred genetic tests done each year
on pregnant women who were 37 years or older, to see
if they were carrying a fetus with Down syndrome. As
the numbers of women interested in these tests grew,
services were expanded and a system was set up to
examine the ndings and determine the pregnancy
outcomes. I had to be trained in data collection and
analysis, because my undergraduate Science degree and
graduate laboratory genetics skills were not enough. I
did a one-year postgraduate course in Epidemiology
and Biostatistics at the University of Melbourne, and
went on to do a PhD in Epidemiology, from 1992 to
1995, using all the data I collected on the prenatal diag-
nostic tests (amniocentesis (amnio) and chorionic villus
sampling (CVS)) undertaken by pregnant women.
A peak in the number of these tests performed in
Victoria was reached in 1998 when over 5000 tests
were done, representing about 9 per cent of all pregnant
women mainly older women. Since then, more
younger women have had these tests because they are
now available to all pregnant women. In 2004, about
60 per cent of all pregnant women had a screening test.
Prenatal screening tests involve testing blood from
the mother, and the results can suggest that the fetus
may have Down syndrome. However, the diagnostic
test (amnio or CVS) is needed to conrm whether or
not the fetus is truly affected. This means that younger
women who have had an abnormal result from their
screen test have added to the number of diagnostic tests
being done. By 2004, almost half of prenatal diagnostic
tests done were to follow up these abnormal screening
test results.
The numbers from our data collection can be used to
plan and fund genetic services, help us understand what
women are experiencing during pregnancy and provide
data to give back to women and their partners for
their use in deciding whether or not to have a prenatal
screening or diagnostic test.
Associate Professor Jane Halliday epidemiologist
BIOLOGY IN THE WORKPLACE
Figure 9.58 Associate Professor Jane Halliday
A pedigree uses symbols to show the pattern of appearance of an
inherited trait across several generations.
Features of the pattern of inheritance of a trait may allow conclusions
to be drawn regarding its mode of inheritance.
Common modes of inheritance are autosomal dominant, autosomal
recessive, X-linked dominant or X-linked recessive.
KEY IDEAS
25 In a family, all persons showing a disorder have at least one parent
who also shows the disorder. Suggest a likely mode of inheritance.
26 Two unaffected parents have a child affected by an inherited disorder.
Suggest a likely mode of inheritance.
27 A man showing a dominant trait has a daughter who does not show
the trait. Could this be an X-linked dominant trait? Explain.
QUICK-CHECK
Data collection is only part of our role. Staff of
Public Health Genetics also conduct surveys and inter-
views, and even provide a randomised trial of a decision
aid for GPs to give pregnant women at their rst ante-
natal visit to help them decide which test(s) to have, if
any. Pregnancy potentially involves lots of testing these
days, and women must be informed about all their
options. We play a role in ensuring this is possible.
We have also been involved in a study of an inher-
ited blood disorder called haemochromatosis, which
is an accumulation of iron in the blood that can lead
to ill health and organ failure. Approximately 1 in 300
people have the genetic change, but the condition can
be treated very simply by regularly donating blood,
thereby preventing the iron build-up. Because this is
such a successful primary prevention technique, we set
out to screen over 12 000 people in their workplace in
a two-year period, looking for this genetic change. The
genetic education and counselling experts made sure
people had enough information to understand and make
a decision about whether or not to have the genetic
test, and we epidemiologists used questionnaires to
survey the population being offered the test. Our work
described the population offered the testing, their
reasons for having or not having a test, and what people
understood about the test and the possible results. There
is now a project looking at the feasibility and accept-
ability of giving this test to school-age children, so we
will again play a role in surveying the population being
tested to make sure the service is working well, from
both the laboratory and community perspective.
We are trained to collect and analyse population-
based data related to genetic testing that will provide
evidence for or against a hypothesis. The hypothesis
might be that a test is working, that a birth defect is
caused by some genetic factor, or that people in the
community will benet from a particular genetic test.
In the world of genetics and with the technological
advances that accompany our growing knowledge, the
impact on public health is potentially very large. Epi-
demiologists will be able to measure this impact and
inuence those creating and using the technology. It is
a very exciting area to work in.
BIOCHALLENGE
1
Human chromosomes
a Where are the following genes HD, DMD,
F8C and HBB located? Indicate this by
labelling the relevant chromosome with its
number and by writing the gene loci that
occur on that chromosome.
b Which of these chromosomes, as a
trisomy, causes the most common human
chromosomal abnormality?
c In a normal human gamete, how many
copies would be expected of each of the
chromosomes represented by this gure?
d Would these chromosomes be single- or
double-stranded chromosomes?
2
Human pedigree
a What mode of inheritance is shown for the
trait in this pedigree?
b What evidence supports your decision in
part a?
c If a fourth child of II5 and II6 were also
to be affected, would it change your
conclusion in part a?
d If II2 were affected, would it change your
conclusion?
3
ABO blood typing
Gavins blood agglutinates only when anti-A
antibodies are mixed with a sample of his
blood. Sally, his wife, shows agglutination only
when anti-B antibodies are added to a sample
of her blood. A blood sample from their rst
child, Kylie, shows no agglutination with either
antibody. Their newborn son is about to be
blood typed.
a What are the ABO phenotypes of each of
Sally, Gavin and Kylie?
b What are the ABO genotypes of each of Sally,
Gavin and Kylie?
c Which of the blood types A, B, AB, O
could their son be? Explain.
I
II
III
1 2
1 2 3 4 5
1 2 3 4 5 6
ANTI-A
ANTI-B
ANTI-A
+
ANTI-B
1 2 3 4 5
CHAPTER REVIEW
1 Demonstrating knowledge Where would you locate each of the following:
a human cells undergoing meiosis?
b haploid cells in a cat?
c cells containing 20 unpaired chromosomes in a mouse?
d the genetic instruction for your ABO blood type?
2 Demonstrating your understanding Use words and/or diagrams to identify
the differences, if any, between the items in each of the following pairs:
a haploid and diploid
b autosome and sex chromosome
c somatic cell and germline cell
d gene and allele
e monohybrid and dihybrid cross.
3 Making connections between concepts Draw a concept map that contains
at least eight key words from this chapter. You may add any other concepts
that you need.
4 Making distinctions Which of the following entries refer to a gene? Which
refer to the particular alleles of a gene?
a the . . . that controls eye colour in humans
b the . . . that produces blue eye colour in humans
c the . . . that produces non-blue eye colour
Key words
Questions
CROSSWORD
albinism
alleles
amniocentesis
asexual reproduction
autosomes
carrier
centromere
chorionic villus sampling (CVS)
chromosome map
chromosomes
co-dominance
crossing over
crossover
deletion
deoxyribonucleic acid (DNA)
dihybrid cross
diploid
disjunction
dominant
Down syndrome (DS)
duplication
egg
embryo
fetus
gamete
gene
gene assortment
genetic counselling
genotype
germline cells
gonads
haploid
hemizygous
heterozygous
homologous
homozygous
ideogram
karyotype
kinetochore
linked
locus
meiosis
mitochondrial genes
monohybrid cross
monosomy
multiple alleles
non-crossover
non-disjunction
non-homologous
ovaries
parental
pedigree
phenotype
recessive
recombinant
recombination
sex chromosomes
sexual reproduction
somatic cells
sperm
synapse
telomeres
test cross
testes
traits
translocation
trisomic
vertebrates
X-inactivation
X-linked
Y-linked
5 Recognising patterns A new-born baby showed facial abnormalities and
other signs including deformed kidneys and nails, and an unusual way of
clenching its fist. Its karyotype was prepared (see figure 9.59). Examine this
karyotype.
a What is the total number of chromosomes?
b What is the sex of the baby?
c What abnormality is visible in the karyotype?
d What name is given to this condition?
Figure 9.59
6 Applying understanding in a new context In cats, one autosomal gene
controls fur length with short fur (S) being dominant to long fur (s). A
second autosomal gene unlinked to the first controls the density of colour
and has the alleles black (D) and grey (d).
a Is either of these genes located on one of the sex chromosomes?
A grey cat with long fur (cat 1) is crossed with a black cat with short fur
(cat 2).
b Write the genotype of cat 1 and draw a simple chromosomal picture
showing this genotype.
c What is the phenotype of cat 2?
d How many kinds of gametes can cat 1 produce?
e List all possible genotypes for cat 2.
f If cat 2 produced many kittens and, regardless of the phenotype of the
other parent, the kittens were always black and short furred, what does
this suggest about the genotype of cat 2?
7 Developing and evaluating hypotheses In a certain breed of dog, the
coat colouring is either black or brown (also known as liver). A number of
observations were made about this breed as follows:
Brown by brown matings always produced brown pups.
Black by black matings sometimes produced all black pups, but in other
similar matings produced both black and brown pups.
Suggest a possible genetic basis for this colouring in dogs.
8 Applying principles Consider the mating between two cats: ss dd Ss Dd.
Draw a Punnett square showing possible kittens and their chance of occur-
rence.
9 Recognising patterns Examine the pedigrees in figure 9.60 and suggest the
most likely pattern(s) of inheritance for each trait. Explain your choice(s).
10 Applying principles Make simple drawings to show the relevant chromo-
some pair(s) and appropriate alleles for the following persons (refer to table
9.7 for allele symbols):
a a man with normal colour vision
b a woman with normal colour vision, but who is a carrier of colour vision
defect
c a person with AB blood type and Rhesus negative
d a boy with Duchenne muscular dystrophy
e a person with normal haemoglobin but whose father had thalassaemia.
11 Making predictions For persons (a) and (b) in question 10 above:
a Identify the types of gametes that they would be expected to produce.
b What different kinds of children in terms of colour vision capability could
they produce?
c Could this couple produce a colour-blind daughter? Explain.
12 Demonstrating your understanding Two genes located close on the
number-9 chromosome are the ABO gene, with the alleles I
A
, I
B
and i, and
the NP1 gene, with the alleles N (deformed nails) and n (normal nails). Fred
is blood type O and is homozygous for normal nails. Gina is blood type AB
and is heterozygous for deformed nails.
a What is Freds genotype?
b Draw Freds pair of number-9 chromosomes showing the arrangement of
the alleles of the two genes.
c What kind(s) of sperm can Fred produce?
d What is Ginas genotype?
e Draw Ginas pair of number-9 chromosomes showing a possible arrange-
ment of the alleles of the two genes.
f What kinds of parental (non-crossover) eggs can Gina produce?
g What kinds of recombinant (crossover) eggs can Gina produce?
h Will crossing over affect the kinds of sperm that Fred produces?
Explain.
13 Applying principles Consider the typical features in the pedigree for
inheritance of an X-linked dominant trait. Explain how this pattern would
change if all affected males died in infancy.
14 Interpreting data A test cross between a heterozygous curly, green-leafed
plant, genotype Kk Gg, and a recessive straight, red-leafed plant, genotype
kk gg, produced the following results:
curly, green: 42 straight, red: 38
curly, red: 5 straight, red: 5
a Do the results support the conclusion that the genes for leaf shape and leaf
colour are linked? Explain.
b What result would be expected if the two genes were not linked but
assorted independently?
Figure 9.60
(a)
(b)
15 Using the web Go to www.jaconline.com.au/natureofbiology/natbiol2-3e
and click on the Chromosome 4 weblink for this chapter. Answer the
following questions.
a What is the likely number of genes of chromosome 4?
b How many base pairs are in the DNA that makes up chromosome 4?
c What percentage of the total DNA of the chromosomes is represented by
chromosome 4?
d What is an ideogram?
Under the diagram on this web page there is a link called How do geneti-
cists indicate the location of a gene?. Click on this link to answer the
following question.
e Where would you look for:
i 5q?
ii Xp?
iii 4q26?
16 Using the web Go to www.jaconline.com.au/natureofbiology/natbiol2-3e
and click on the Centromeres weblink for this chapter. Check on the role
of the centromere and its kinetochore in chromosome movement.
a How long is the base sequence that is repeated in the region of the
centromere?
b About how many base sequences in total make up the centromere of a
human chromosome?
c What is the most common fate of an embryo that has an unbalanced set
of chromosomes?

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