Genetics timeline

1882
German biologist Walter Fleming
discovers rod-shaped bodies he
calls "chromosomes

1902
Walter Sutton demonstrates that
chromosomes exist in pairs
In light of Mendel's theory that
genetic "factors" segregate, he
concludes that hereditary factors
must lie on chromosomes
 Genotype: encoded in chromosomes

Chromosome - a long strand of DNA, packaged together with

proteins and other molecules

Number of
Organism Chromosome
Pairs
Tomato 12 Pairs
Mouse 20 Pairs
Human 23 Pairs
Dog 39 Pairs
 Basic chromosome structure
During mitosis or meiosis,
chromosomes condense,
become visible under the
microscope
Centromere
Region where spindle fibers attach
and move the chromosome during
mitosis or meiosis
essential for segregation
Chromatid
of a replicated chromosome
2 sister chromatids in replicated
chromosome

3
 The human genome

Humans have 23
chromosome pairs
consisting of 2 types:

1. Sex chromosomes -
determine the sex of
an individual
XX or XY

2. Autosomal
chromosomes
22 pairs
 Cell types
Somatic cells (2n) form the body of the organism

Germ cells form the sex cells needed for sexual

reproduction
Egg = from ovaries
Sperm = from testes

The egg and sperm fuse (fertilization) to form the

zygote (2n) which gives rise to the new organism

The genetic material in the germ cells determine

heredity
 Haploid genome Diploid genome
Refers collectively to the Refers to both copies of
single copy of all all chromosomes
chromosomes Same diploid genome
Found in sex cells found in all non-sex cells
Sperm in a given individual
Egg
 The cell cycle
During a cell cycle, a cell

1. grows (the G1 gap)

2. prepares for division
(the S phase)
3. continues to function
for a while (G2 phase)
4. divides to form two
daughter cells (M
phase)
 The eukaryotic cell cycle
During G1, S, and G2 phases, the cell grows continuously.
During M phase growth stops, the nucleus divides, and the
cell divides in two.
DNA replication is confined to S phase.
 2 types of cell divison
Meiosis Mitosis
Gives rise to haploid Gives rise to diploid
genome genome
4 daughter cells of 2 daughter cells of
meiosis are NOT mitosis are
genetically identical genetically
equivalent
Somatic cells undergo mitosis
 4 stages of mitosis
1. Prophase: condensation of chromosomes
2. Metaphase: the spindle forms, attaches to
kinetochore
3. Anaphase: sister chromatids move towards
opposite poles
4. Telophase: two new nuclei form, chromosomes
decondense

Cytokinesis = process by which the cytoplasm divides

Stages of
mitosis
 Meiosis in sex cells
Process that produces haploid
gametes from diploid cells

Reduces no. of chromosomes

to half of that in the non-sex
cells
Homologous chromosomes
which exist in diploid cells are
separated

Before meiosis starts, cells

have already undergone DNA
replication

Egg and sperm cells

Meiosis 1

Reductional
division
reduces the
chromosome
number by
half
In the first stage
of meiosis,
homologous
chromosomes,
NOT
chromatids,
separate

15
Meiosis 2

Produces 4
haploid cells

Takes place
place
without DNA
replication
Dosage compensation by X inactivation
Dosage Compensation = dosage equalization for active genes
Having twice as much dosage may be deleterious; too much of a gene
product is made

For genes on the X chromosome, 2 copies in females, 1 copy in

males

X inactivation: one copy of X is randomly inactivated in all

somatic cells of females
Females are genetic mosaics for genes on the X chromosome
only one X allele is active in each cell

Barr body = inactive X chromosome in the nucleus of

interphase cells
X-chromosome
inactivation
 Mosaics

White fur results from action of another gene

How does X Inactivation affect an X-linked
trait like Hemophilia?

XH = make the clotting Factor VIII

Xh = does not make clotting Factor VIII
Your blood clots fine with half as much
Factor VIII
Liver cells make Factor VIII
Compare XHXH homozygote with XHXh
heterozygote

20
What we get from our parents
Each cell contains the same genetic material
 Chromosomal abnormalities

Genetic anomalies in which an individual may

have
1. An atypical number of chromosomes (karyotype)
2. a structural abnormality in one or more
chromosomes

Chromosome anomalies usually occur when

there is an error in cell division following
meiosis or mitosis.
Types of chromosome
abnormalities
Chromosome deletion syndromes
cri du chat syndrome
part of chromosome 5 is missing
small head with many abnormal features
round face
small jaw
wide nose
widely separated eyes
ears set low in the head
has a high-pitched cry that sounds like a kitten crying
Mental, physical development are greatly retarded
Cri du chat syndrome
Prader-Willi syndrome
symptoms vary
according to the child's
age
Newborns feel limp,
feed poorly, and gain
weight slowly
between 1 6 years,
appetite increases, often
becoming insatiable
Obsessive-compulsive
behaviors are common
Weight gain is excessive
 Chromosome duplication
if the deleted fragment joins the homologous
chromosome, then that region is repeated
e.g., Fragile X
most common form of mental retardation
X chromosome of some people is unusually fragile at one
tip - seen "hanging by a thread" under a microscope
Normal people have 29 "repeats" at this end of their X-
chromosome
those with Fragile X have over 700 repeats due to
duplications
affects 1:1500 males, 1:2500 females.
Fragile X syndrome
 Abnormalities of Chromosome
Number
usually a result
of
nondisjunction
errors during
meiosis
not inherited
Nondisjunction in Meiosis I and Meiosis II
Irregular number of chromosomes
variation in the number of chromosomes from
the normal 46
Aneuploidy: extra copy or a missing copy of a
chromosome
May be
1. Trisomy 3 copies of a chromosome
- e.g., Down syndrome
2. Monosomy - one copy of a certain chromosome
 Down syndrome characteristics

short, stocky bodies with thick hands and feet

simian crease
broad, short heads with small low-set ears
relatively large ridged tongues that roll over a
protruding lower lip
eyes have an East Asian-like appearance due to
an epicanthic fold
 Down syndrome: medical problems
epilepsy
hypothyroidism
crossed eyes
near-sightedness or far-sightedness
Cataracts
hearing impairment
heart defects
intestinal malformations
susceptibility to respiratory infections, e.g., pneumonia
Mental retardation

Abnormal traits a result of the over expression of the

involved genes
 Sex chromosome abnormalities

slightly less common than autosomal

abnormalities
usually much less severe in their effects

Female Male
Syndrome Syndrome
Genotype Genotype
XX normal XY normal
XO Turner XXY Klinefelter
XXX Triple-X XYY XYY
 Female chromosome abnormalities

Turner syndrome
~1:3,000 to 5000 female infants
genotype is X0
Short, have distinctive webbed necks , small jaws,
and high arched palates
lack prominent female secondary sexual
characteristics
exceptionally small, widely spaced breasts, broad
shield-shaped chests, and turned-out elbows
ovaries do not develop normally
estrogen replacement therapy can result in some
breast development and menstruation
Turners syndrome
 Metafemales , or triple-X females
~1:1000 female infants
genotype is XXX
Usually taller than average with unusually long legs
and slender torsos, but otherwise appear normal
normal development of sexual characteristics and
are fertile.
may have slight learning difficulties
usually in the low range of normal intelligence
tend to be emotionally immature for their size during
childhood
 Male sex chromosome abnormalities

Klinefelter syndrome
genotype is XXY
relatively high-pitched voices, asexual to
feminine body contours, little facial and body
hair
testes and prostate gland are small; produce
relatively small amounts of testosterone.
likely to be overweight
usually have learning difficulties as children,
especially with language and short-term memory
Klinefelter syndrome
 XYY syndrome
1 in 900 male births to as rare as 1 in 1500
usually tall (>6 feet) and generally appear and act normal
produce high levels of testosterone
during adolescence, they often are slender, have severe
facial acne, and are poorly coordinated
usually fertile and lead ordinary lives as adults
Sex chromosome abnormalities
 Consequences of numerical
chromosomal abnormalities
1. Polyploidy Triploidy (69,XXX, XXY or XYY)
13% of all conceptions
almost never liveborn; do not survive

2. Aneuploidy
one chromosome missing)
Embryonic lethal
a) trisomy (one extra chromosome)
Usually embryonic or fetal lethal
Trisomy 13 (Patau syndrome) and trisomy 18 (Edwards
syndrome) may survive to term
Trisomy 21 (Down syndrome) may survive to age 40 or
longer
3. Sex chromosomes XXX, XXY, XYY
Relatively minor problems
normal lifespan
45,X Turner syndrome - 99% abort spontaneously
survivors are of normal intelligence but infertile and
show minor physical signs
 ~2/3 of human triploids arise by fertilization of a single egg by two
sperm (A). Other causes are a diploid egg (B) or sperm (C). Most
human triploids abort spontaneously; very rarely they survive to term,
but not beyond.
Tetraploidy (D) results from failure to divide after fertilization, and is
incompatible with development.
Risk for chromosomal abnormalities
increases with maternal age

48
Amniocentesis
Weeks 14 to 16 of pregnancy
Risk of miscarriage is 1/300

Arrest cells in metaphase (block mitosis)

Perform karyotype
 Inheritance of chromosomal
abnormalities
Most chromosome anomalies occur as an
accident in the egg or sperm
not inherited

Some anomalies can happen after conception,

resulting in mosaicism (where some cells have
the anomaly and some do not)
 Mosaics and chimeras
1. Mosaics
2 or more genetically different cell lines derived
from a single zygote
change indicated may be a gene mutation, a
numerical or structural chromosomal change

2. Chimera
derived from two zygotes
usually both normal but genetically distinct.