Chromosomes and

Human Genetics

Chromosomes & Cancer

Some genes on chromosomes control
cell growth and division
If something affects chromosome
structure at or near these loci, cell
division may spiral out of control
This can lead to cancer

Philadelphia Chromosome
First abnormal chromosome to be

associated with a cancer

Reciprocal translocation

Causes chronic myelogenous leukemia

(CML)

Genes
Units of information about heritable
traits

In eukaryotes, distributed among

chromosomes
Each has a particular locus
Location on a chromosome

Homologous Chromosomes
Homologous autosomes are identical in
length, size, shape, and gene sequence
Sex chromosomes are nonidentical but
still homologous
Homologous chromosomes interact,
then segregate from one another during
meiosis

Alleles
Different molecular forms of a gene
Arise through mutation
Diploid cell has a pair of alleles at each
locus

Alleles on homologous chromosomes

may be same or different

18.1 Chromosomes

Chromosomes: A review

Humans have 46 chromosomes that are in 23 pairs

within a cells nucleus
Pairs of chromosomes are called homologous chromosomes
Autosomes are the 22 pairs of chromosomes that control traits
that do not relate to gender of an individual
Sex chromosomes are the 1 pair that contains the genes that do
control gender

Cells (body cells) that have 46 (2N) chromosomes are

called diploid

Cells (sex cells) that have only 23 (N) chromosomes not

in pairs are called haploid

Sex Chromosomes
Discovered in late 1800s
Mammals, fruit flies
XX is female, XY is male

In other groups XX is male, XY female

Human X and Y chromosomes function

as homologues during meiosis

Karyotype Preparation Stopping the Cycle

Cultured cells are arrested at
metaphase by adding colchicine
This is when cells are most condensed
and easiest to identify

Karyotype Preparation
Arrested cells are broken open
Metaphase chromosomes are fixed
and stained
Chromosomes are photographed
through microscope

Photograph of chromosomes is cut

up and arranged to form karyotype
diagram

18.1 Chromosomes

What is a karyotype?
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

sister
chromatids
centromere

homologous
autosome pair

sex chromosomes
in males

The 46 chromosomes of a male

CNRI/SPL/Photo Researchers, Inc.

Karyotype Diagram

13

14

15

16

17

18

19

20

21

10

22

11

12

XX (or XY)

Figure 12.4
Page 197

Sex
Determination

Figure 12.5
Page 198

female
(XX)

male
(XY)

eggs

sperm

XX

XX

XY

XY

The Y Chromosome
Fewer than two dozen genes identified
One is the master gene for male sex
determination
SRY gene (sex-determining region of Y)

SRY present, testes form

SRY absent, ovaries form

Effect of Y
Chromosome

appearance of structures
that will give rise to
external genitalia

appearance of
uncommitted duct system
of embryo at 7 weeks

7 weeks
Y
present

Y
absent

Y
present

Y
absent

testes

ovaries

10 weeks

ovary

Figure 12.6
Page 199

birth approaching

testis

The X Chromosome
Carries more than 2,300 genes

Most genes deal with nonsexual traits

Genes on X chromosome can be
expressed in both males and females

Discovering
Linkage

homozygous dominant
female

recessive male

Gametes:
X

All F1
have red eyes
Gametes:

x
X

X
1/2

1/2

1/4

1/2
F2
generation:

1/2
1/4

1/4
1/4

Figure 12.7
Page 200

Linkage Groups
Genes on one type of chromosome
Fruit flies
4 homologous chromosomes
4 linkage groups

Not all genes on chromosome are

tightly linked

Full Linkage
B

Parents:

A
AB

a
b

F1 offspring:

ab

All AaBb

meiosis, gamete formation

Equal ratios of two

types of gametes:

A
B

50% AB

a
b

50% ab

Figure 12.8a
Page 201

Incomplete Linkage
AC

A
C

Parents:

ac

a
c

C
F1 offspring:

All AaCc
meiosis, gamete formation

Unequal ratios of four

types of gametes:

A
C

parental
genotypes

A
c

recombinant
genotypes

Figure 12.8b
Page 201

Crossover Frequency
Proportional to the distance that
separates genes
A

Crossing over will disrupt linkage between

A and B more often than C and D
In-text figure
Page 201

Linkage Mapping in Humans

Linkage maps based on pedigree
analysis through generations
Color blindness and hemophilia are very
closely linked on X chromosome

Pedigree
Symbols

male
female
marriage/mating

offspring in order of birth,

from left to right

Individual showing trait

being studied
sex not specified

I, II, III, IV...

Figure 12.9a
Page 202

generation

Pedigree for Polydactyly

female

male

II
5,5
6,6

III

IV

5,5
6,6
6

6,6
5,5

5,5
6,6

5,5
6,6

5,5
6,6

5,5
6,6

5,6
6,7
12

*Gene not expressed in this carrier.

Figure 12.9b
Page 202

6,6
5,5

6,6
6,6

Genetic Abnormality
A rare, uncommon version of a trait

Polydactyly
Unusual number of toes or fingers
Does not cause any health problems
View of trait as disfiguring is subjective

Genetic Disorder
Inherited conditions that cause mild to
severe medical problems

Why dont they disappear?

Mutation introduces new rare alleles
In heterozygotes, harmful allele is masked,
so it can still be passed on to offspring

Autosomal Recessive
Inheritance Patterns
If parents are
both
heterozygous,
child will have a
25% chance of
being affected
Figure 12.10a
Page 204

20.3 Inheritance of genetic disorders

Autosomal recessive disorder

Individuals must be homozygous recessive to
have the disorder
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

aa

II

III

IV

A?

A?

Aa

Aa

A?

relatives

Aa

Aa

aa

aa

Autosomal recessive disorders

Affected children can have
unaffected parents.

A?

A?

Key

A?

aa = affected
Aa = carrier (unaffected)
AA = unaffected
A? = unaffected
(one allele unknown)

Heterozygotes (Aa) have an unaffected phenotype.

Two affected parents will always have affected children.
Affected individuals with homozygous unaffected mates will have
unaffected children.
Close relatives who reproduce are more likely to have
affected children.
Both males and females are affected with equal frequency.

Galactosemia
Caused by autosomal recessive allele
Gene specifies a mutant enzyme in the
pathway that breaks down lactose
enzyme 1

lactose

In-text figure
Page 204

enzyme 3

enzyme 2

galactose
+
glucose

galactose-1phosphate

galactose-1phosphate

intermediate
in glycolysis

Autosomal
Dominant Inheritance
Trait typically
appears in
every
generation

Figure 12.10b
Page 204

20.3 Inheritance of genetic disorders

Autosomal dominant disorder

Individuals that are homozygous dominant and
heterozygous will have the disorder
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Aa

Aa

*
II

III

Aa

aa

Aa

Aa

A?

aa

Autosomal dominant disorders

aa

aa

aa

aa

aa

aa

Key
AA = affected
Aa = affected
A? = affected
(one allele unknown)
aa = unaffected

Affected children will usually have

an affected parent.
Heterozygotes (Aa) are affected.
Two affected parents can produce an unaffected child.
Two unaffected parents will not have affected children.
Both males and females are affected with equal frequency.

20.3 Inheritance of genetic disorders

Genetic disorders of interest

Tay-Sachs disease: lack of the enzyme that breaks down lipids in
lysosomes resulting in excess and eventually death of a baby
Cystic fibrosis: Cl- do not pass normally through a cell membrane
resulting in thick mucus in lungs and other places often causing
infections

Phenylketonuria (PKU): lack of an enzyme needed to make a certain

amino acid and affects nervous system development
Sickle-Cell disease: red-blood cells are sickle shaped rather than
biconcave that clog blood vessels
Huntington disease: huntington protein has too many glutamine
amino acids leading to the progressive degeneration of brain cells

20.3 Inheritance of genetic disorders

Genetic disorders
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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

H2O

Cl

Cl

Cl
H2O

Cl
H2O

Cl

nebulizer

many neurons in
normal brain
defective
channel

percussion
vest

loss of neurons in
huntington brain
(both brain tissue slides): Courtesy Dr. Hemachandra Reddy, The Neurological Science Institute, Oregon Health
& Science University; (woman with Huntington): Steve Uzzell

thick mucus

Pat Pendarvis

Huntington Disorder
Autosomal dominant allele
Causes involuntary movements, nervous
system deterioration, death
Symptoms dont usually show up until person
is past age 30
People often pass allele on before they know
they have it

Achondroplasia
Autosomal dominant allele
In homozygous form usually leads to
stillbirth
Heterozygotes display a type of dwarfism
Have short arms and legs relative to other
body parts

20.5 Sex-linked inheritance

Sex-linked inheritance
Traits are controlled by genes on the sex
chromosomes
X-linked inheritance: the allele is carried on
the X chromosome
Y-linked inheritance: the allele is carried on
the Y chromosome
Most sex-linked traits are X-linked

X-Linked Recessive
Inheritance
Males show
disorder more
than females
Son cannot inherit
disorder from his
father
Figure 12.12a
Page 205

Examples of X-Linked Traits

Color blindness
Inability to distinguish among some of all
colors

Hemophilia
Blood-clotting disorder

1/7,000 males has allele for hemophilia A

Was common in European royal families

20.5 Sex-linked inheritance

X-linked inheritance: Color blindness

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Parents

XBY

Possible offspring:
XBXB normal vision female
XBXb normal vision female
XBY normal vision male
XbY normal vision male

XBY

XBXb

eggs

XB

XB

Xb

XBXB

XBXb

Key
XB = Normal vision
Xb = Color-blind
Normal vision
Color-blind

Phenotypic Ratio
Females All

sperm

Cross:
XBXb x

XBY
Offspring

XbY

Males 1:1 1
1

20.5 Sex-linked inheritance

X-linked disorders
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

XBXB

XBY

XbY

XBXb daughter

grandfather

XBY

XbXb

XbY

XBY

XBXB

XBXb

XbY

grandson

Key
XBXB = Unaffected female
XBXb = Carrier female
XbXb = Color-blind female
XBY = Unaffected male
XbY = Color-blind male

X-linked Recessive
Disorders
More males than females are affected.
An affected son can have parents who have the
normal phenotype.
For a female to have the characteristic, her father
must also have it. Her mother must have it or be a
carrier.
The characteristic often skips a generation from the
grandfather to the grandson.
If a woman has the characteristic, all of her sons will
have it.

20.5 Sex-linked inheritance

X-linked disorders: Hemophilia

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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Unaffected female

Unaffected male
Victoria Edward

Carrier female

Hemophiliac male

Albert

Victoria

Alice Louis IV

Alexandra

?
Olga

Nicholas II

10

Leopold

Beatrice

Mary

Helena

Marie
Alexi
Tatiana
Anastasia

?
9

Juan Carlos
5

All were assassinated

6
1. Victoria
2. Edward VII
3. Irene
4. George V
6. Margaret
7. Victoria
8. Alfonso XIII
9. Juan

Philip Elizabeth II

12

William

11

13

16

14

15

Harry

(queen): Stapleton Collection/ Corbis; (prince): Huton Archive/Getty Images

10. Alexandra
11. Charles
12. Diana
13. Andrew
14. Edward
15. Anne
16. Sarah

Fragile X Syndrome
An X-linked recessive disorder
Causes mental retardation

Mutant allele for gene that specifies a

protein required for brain development
Allele has repeated segments of DNA

Hutchinson-Gilford Progeria
Mutation causes accelerated aging
No evidence of it running in families

Appears to be dominant
Seems to arise as spontaneous
mutation
Usually causes death in early teens

18.6 Chromosome inheritance

Changes in chromosome structure

Deletions loss of a piece of the chromosome (e.g.,

Williams syndrome)

Translocations movement of chromosome segments

from one chromosome to another nonhomologous
chromosome (Alagille syndrome)

Duplications presence of a chromosome segment

more than once in the same chromosome

Inversions a segment of a chromosome is inverted

180 degrees

Duplication
Gene sequence that is repeated several
to hundreds of times

Duplications occur in normal

chromosomes
May have adaptive advantage
Useful mutations may occur in copy

Duplication
normal chromosome

one segment
repeated
three repeats

Inversion
A linear stretch of DNA is reversed
within the chromosome
segments
G, H, I
become
inverted

In-text figure
Page 206

Translocation
A piece of one chromosome becomes
attached to another nonhomologous
chromosome
Most are reciprocal
Philadelphia chromosome arose from a
reciprocal translocation between
chromosomes 9 and 22

Translocation
one chromosome

a nonhomologous
chromosome

nonreciprocal translocation
In-text figure
Page 206

In-text
figure
Page 206

Deletion
Loss of some segment of a chromosome
Most are lethal or cause serious disorder

18.6 Chromosome inheritance

Changes in chromosome structure

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

a
b
c

a
b
c

b
c
+

a
d

a
b
c

a
b
c

a
b
d

l
m
n

l
m
n

g
h

g
a. Deletion

b. Duplication

c. Inversion

a
b
c

c
e

a
b
c

d. Translocation

18.6 Chromosome inheritance

Changes in chromosome number

Nondisjunction occurs when both members of a
homologous pair go into the same daughter cell
during meiosis I or when sister chromatid fails
to separate in meiosis II.

Results of nondisjunction:
Monosomy: cell has only 1 copy of a chromosome
e.g., Turner syndrome (only one X chromosome)

Trisomy: cell has 3 copies of a chromosome

e.g., Down syndrome (3 copies of chromosome 21)

Aneuploidy
Individuals have one extra or less
chromosome
(2n + 1 or 2n - 1)
Major cause of human reproductive
failure
Most human miscarriages are
aneuploids

Polyploidy
Individuals have three or more of each
type of chromosome (3n, 4n)

Common in flowering plants

Lethal for humans
99% die before birth
Newborns die soon after birth

Nondisjunction
n+1

n+1

n-1

chromosome
alignments at
metaphase I

n-1
nondisjunction alignments at
at anaphase I metaphase II

anaphase II
Figure 12.17
Page 208

Down Syndrome
Trisomy of chromosome 21
Mental impairment and a variety of
additional defects
Can be detected before birth
Risk of Down syndrome increases
dramatically in mothers over age 35

18.5 Chromosome inheritance

Changes in sex chromosome number

Turner syndrome (X) short stature, broad shouldered with folds of

skin on the neck, underdeveloped sex organs, no breasts

Klinefelter syndrome (XXY) underdeveloped sex organs, breast

development, large hands and long arms and legs

Poly-X female (XXX, XXXX)

XXX tends to be tall and thin but not usually retarded

XXXX are severely retarded

Jacobs syndrome (XYY) tall, persistent acne, speech and reading

problems

18.5 Chromosome inheritance

Changes in sex chromosome number

Turner Syndrome
Inheritance of only one X (XO)
98% spontaneously aborted

Survivors are short, infertile females

No functional ovaries
Secondary sexual traits reduced

May be treated with hormones, surgery

Klinefelter Syndrome
XXY condition
Results mainly from nondisjunction in
mother (67%)
Phenotype is tall males
Sterile or nearly so
Feminized traits (sparse facial hair,
somewhat enlarged breasts)
Treated with testosterone injections

XYY Condition
Taller than average males
Most otherwise phenotypically normal

Some mentally impaired

Once thought to be predisposed to
criminal behavior, but studies now
discredit

Phenotypic Treatments
Symptoms of many genetic disorders
can be minimized or suppressed by
Dietary controls
Adjustments to environmental conditions
Surgery or hormonal treatments

Genetic Screening
Large-scale screening programs detect
affected persons

Newborns in United States routinely

tested for PKU
Early detection allows dietary intervention
and prevents brain impairment

Prenatal Diagnosis
Amniocentesis

Chorionic villus sampling

Fetoscopy
All methods have some risks

Preimplantation Diagnosis
Used with in-vitro fertilization
Mitotic divisions produce ball of 8 cells

All cells have same genes

One of the cells is removed and its
genes analyzed
If cell has no defects, the embryo is
implanted in uterus