INTERNATIONAL UNIVERSITY FOR

SCIENCE & TECHNOLOGY

GENETICS lecture course

Dr. A. Rahmo
PhD. Biochemistry and Molecular biology USC

GENETICS COURSE LECTURES

1- INTRODUCTION
2- MONOGENIC INHERITANCE (ONE GENE)
3- MONOGENIC INHERITANCE (TWO GENES)
4- PEDIGREE ANALYSIS
5- BEYOND CLASSICAL (MENDELIAN) GENETICS
6- EXAM
7-POLYGENIC INHERITANCE
8- CYTOGENETICS
9- MOLECULAR GENETICS OF PROCARYOTES
10- MOLECULAR GENETICS OF EUCARYOTES
11- ONCOGENETICS
12- EXAM
13- TESTING & TREATMENT OF GENETIC DISEASES
14- POPULATION GENETICS
15- REVIEW

Cytogenetics

Cytogenetics
A subdiscipline within genetics
Focuses on chromosome variations
Abnormal number of copies of genes or
chromosomes can lead to genetic
abnormalities
Human genome sequence information is used
to identify genes that contribute to the
chromosome-related syndromes

The Normal Karyotype

Human somatic cells
contain 46 chromosomes
23 diploid chromosomes
paired homologs of
chromosomes 1 to 22
sex chromosomes (XX
or XY)
Diploid - two sets of each
chromosome.
Haploid gametes - one set
of each chromosome
Euploid cells have a normal
chromosome constitution

Karyotypes
Chromosomal
chart
Chromosomes
arranged by size
and structure
24 types
Arranged by
largest to smallest

Three Copies of Chromosome 21

Down Syndrome

Portrait of a Chromosome
Primarily DNA and protein
Described by size and shape
Heterochromatin (dark) contains
mostly repetitive DNA
Euchromatin (light) contains more
protein encoding genes
Contains:
Telomere are chromosome tips
composed of many repeats of
TTAGGG and shorten with each cell
division
Origin of replication sites
Centromere largest constriction of
the chromosome and spindle fibers
attach

Centromeres

Alpha satellite the bases

that form the centromere are
repeats of a 171-base DNA
sequence
Centromere associated
proteins form the
kinetochore that attaches to
spindle fibers
Centromere protein A
(CENP-A) involved in
centromere replication is
passed to next generation
and nearly identical in all
species

Subtelomeres
The chromosome region between
the centromere and telomeres
Consists of 8,000 - 300,000 bases
Includes at least 500 proteinencoding genes
Near telomere the repeats similar
to the telomere sequence
Multigene families that include
pseudogenes (non functioning copies
of working genes)

Chromosome classification:
A- Size:
Chromosomes Differ in Size

B- Shape:
Centromere Position

At tip - telocentric

Close to end- acrocentric

Displaced from center submetacentric

At midpoint metacentric

Long arm q

Short arm p

Chromosomal description
An ideogram represents a
chromosome schematically.
The major banding regions
are indicated with numbers.
Example
Sucrose intolerance is located
at 3q.26
or chromosome 3, long arm,
major band 26)

Chromosome 3

Polyploidy
17% of all spontaneous abortions and 3%
of stillbirths/newborn deaths show
polyploidy

Triploid - three copies of each

chromosome
Produced by:
-Two sperm fertilize one egg.
-Haploid sperm fertilizes diploid
egg

Aneuploidy
Cells with extra or missing chromosomes:
Nondisjunction is a common cause
Gametes produced with one extra chromosome and another with one
missing chromosome
Nondisjunction during Meiosis I results in copies of both homologs in
one gamete
Nondisjunction during Meiosis II results in both sister chromatids in one
gamete

Meiotic nondisjunction

Meiotic nondisjunction. Gametes with an abnormal chromosome number can arise by nondisjunction
in either meiosis I or meiosis II.

Trisomies and Monosomies

Results in extra or missing copies of all of the genes on the
chromosome
Most cease developing as embryos
Some fetuses with trisomy of smaller autosomes survive to birth

Trisomy 21

Down syndrome
Most common of trisomy
Distinctive facial and physical problems
Many medical problems are treatable
Varying degrees of developmental
disabilities
Link with one form of Alzheimer disease
May also be produced by a translocation
Maternal age is a risk factor for having a
child with Down syndrome

Large tongue
Flat face
Slanted eyes
Single crease across palm
Mental retardation
Some are not

Trisomy 13

Patau syndrome

Very rare and generally

do not survive 6 months
Medical and physical
abnormalities
Facial malformation and

eye fusion

Cleft lip and palate

Extra fingers & toes
polydactylism

Defects
Heart
Brain
Kidneys

Most abort
Live span < 1 month

Trisomy 18

Edward syndrome

1 in 6,000-10,000

Most do not

survive

Serious medical
and physical

disabilities

Heart defects
Displaced liver
Low-set ears
Abnormal hands
Severe retardation
98% abort
Lifespan < 1 year

Turner Syndrome (45,X)

Only one copy of X chromosome

1 in 2,000 female births
99% of affected fetuses die in utero
Absence of Y leads to development as a
female
Phenotypes include short stature,
webbing at back of neck, incomplete
sexual development, hearing impairment

Short
Not go through pruberty
Produce little estrogen
Sterile
Extra skin on neck

Klinefelter Syndrome (47,XXY)

1 in 1,000 male births

Extra copy of each X-linked gene
Phenotypes include
incomplete sexual development
rudimentary testes and prostate
long limbs, large hands and feet
some breast tissue development
Some cases are not diagnosed until fertility
problems arise or remain undiagnosed

Breast development
Small testes
Sterile
Low intelligence
Not retarded

Chromosome Structural Abnormalities

Chromosomal deletions or
duplications result in extra
or missing copies of genes

Inversions alter the

sequence of genes

Translocations

deletions
Example: microdeletion

The loss of a tiny piece of a

chromosome, a piece so small
its absence is not apparent on
ordinary examination (using a
regular light microscope to look
at chromosomes prepared in
the usual fashion).
The detection of microdeletions
requires special techniques
such as high-resolution
chromosome banding,
molecular chromosome
analysis

Microdeletions:

1p36 microdeletion syndrome, 1p36 deletion,

Wolf-Hirschhorn, 4p deletion,
Cri-du-Chat, 5p deletion,
Sotos syndrome, 5q deletion,
Williams syndrome, 7q11.23 deletion,
Prader-Willi/Angelman syndrome, 15q11.2
deletion,
15q11.2 duplication syndrome,
Miller-Dieker syndrome, 17p13.3 deletion,
Smith-Magenis syndrome, 17p11.2 deletion,
Neurofibromatosis Type 1, 17q11.2 deletion,
DiGeorge/Shprintzen (VCF) syndrome, 22q11.2
deletion,
Kallmann syndrome, Xp22.3 deletion,
Steroid sulfatase deficiency, Xp22.3 deletion,

A Duplication

Larger regions of deletion or duplication increase the

likelihood that there will be an associated phenotype

Translocation
Nonhomologous chromosome exchange segments
Includes two major types:
Robertsonian translocation
Two nonhomologous acrocentric chromosomes break at the
centromere and long arms fuse. The short arms are often lost.
5% of Down syndrome results from a Robertsonian translocation
between chr 21 and chr14.
Reciprocal translocation
Two nonhomologous chromosomes exchange a portion of their
chromosome arms.

Segregation of a Robertsonian Translocation

Causing aneuploidy

Reciprocal Translocation
Exchange of material from one chromosome arm to
another
Some individuals carry a translocation but are not
missing any genetic material unless a translocation
breakpoint interrupts a gene

Inversions
Inverted chromosomes have a region flipped in orientation
5-10% cause health problems probably due to disruption of
genes at the breakpoints
Inversions may impact meiotic segregation
Two types of inversions occur:
Paracentric
inverted region does NOT include centromere
Pericentric
inverted region includes centromere

Segregation of a Paracentric Inversion

Segregation of a Pericentric Inversion

Isochromosomes
Chromosomes with identical
arms
Form when centromeres divide
along the incorrect plane during
meiosis

Ring Chromosomes
Chromosomes shaped like a ring
Occur in 1 in 25,000 conceptions
May arise when telomeres are
lost and sticky chromosome end
fuse
Ring chromosomes have
phenotypes associated with the
loss or addition of genetic
material

Uniparental Disomy
Inheritance of two
chromosomes from one parent
May occur
When nondisjunction
occurs in both parents (a
disomic gamete and one
without homolog)
Loss or nondisjunction of
one homolog in early
embryo followed by
reduplication of remaining
homolog

Mosaics and Chimeras

A mosaic is an organism which is derived from a
single fertilization but which contains cells with two
or more different chromosome compositions.
For instance, it is possible to be 46,XY / 45,X. Some cells are normal
male (XY) cells, while others are Turner syndrome female cells.
This is caused by chromosome loss or non-disjunction in one of the
first few mitoses of a newly formed embryo.

Trisomy 9
Mosaic

A chimera is an organism which is composed of

two genetically different organisms, which have
fused together.
Usually seen as a person with blood cells from a fraternal twin whose
body was absorbed: a person with two different blood types.
Cheep goat
chimera

Transgenic animals

Human Animal Chimeras

A major bioethical concern