GENETIC BASIS OF DISEASE

Dr A Hussainy
Dr H Yousif
25-11-1435 (19-10-2014)

GENES
A gene is a molecular unit of.. HEREDITY
(passing of trait to offspring from its parents).
GENE is a name given to some areas / segments
of DNA, that code for a polypeptide.

Genotype

v/s

Phenotype

The genetic makeup of

individual

The effects produced by

these genes.

Some More Terms.....

LOCUS: Each gene is situated at a specific site on
one of a pair of chromosomes & the genes
forming a pair are called ALLELES.

Homozygote: If the genes (alleles) are alike.

Heterozygote: If the genes (alleles) are NOT alike.

MODE OF INHERITANCE
Dominant genes
produce effects both
in heterozygote & in
homozygote
members.

Recessive genes
produce their
effects only in
homozygote
members.

Intermediate inheritance

v/s

Co-Dominance

An example for intermediate inheritance is, the patients

with sickle cell anemia, in which the heterozygote has
the sickle-cell trait & differs both from normal individual
& patient with sickle-cell anemia

So, What is a Genetic disorder?

A genetic disorder is a condition

caused by abnormalities in
GENES or CHROMOSOMES.

Types of genetic disorders

1.

Single gene disorders.

2.

Chromosomal disorders.

3.

Complex multigenic disorders.

Types of genetic disorders

1.

Single gene disorders.

2.

Chromosomal disorders.

3.

Complex multigenic disorders.

Single gene disorders

1.

Autosomal dominant (AD)

2.

Autosomal recessive (AR).

3.

Sex-linked gene linked.

Autosomal Dominant Disease

Only one copy of an allele is necessary for

an individual to get the disease.

Appears in both heterozygous &

homozygous members.

The

disease appears in every generation.

Autosomal Dominant Disease

Autosomal dominant
diseases (prevalence)
The three most common AD diseases in the
world.....
1.
2.
3.

Familial hypercholesterolemia (1 in 500)

Polycystic kidney disease (1 in 1250)
Neurofibromatosis type I (1 in 2,500)

Single gene disorders

1.

Autosomal dominant (AD)

2.

Autosomal recessive (AR).

3.

Sex-linked gene linked.

Autosomal Recessive Inheritance

A normal or abnormal genetic trait is
transmitted from parent to offspring, TWO
copies of this gene MUST be present in
order for the trait to develop.
This means that disease occurs only in
homozygous members.

Autosomal recessive
diseases (prevalence)
The three most common AR diseases in the
world.....
1.
2.
3.

Sickle cell anemia (1 in 625)

Cystic fibrosis (1 in 2,000)
Tay-Sachs disease (1 in 3,000)

Sickle Cell Anemia

Single gene disorders

1.

Autosomal dominant (AD)

2.

Autosomal recessive (AR).

3.

Sex-linked gene linked.

Sex-Linked
Gene Inheritance

When gene is
localized on X or Y
chromosome.

Usually recessive & is

on X chromosome.

E.g. Hemophilia

Types of genetic disorders

1.

Single gene disorders.

2.

Chromosomal disorders.

3.

Complex multigenic disorders.

CHROMOSOMAL DISORDERS
Karyotype

Alteration

in number
(increase or decrease)

Or

structural changes
within chromosome

TRISOMY

(increased number)
Presence

of an
additional (3rd)
chromosome in an
otherwise diploid
chromosome
complex.

Total

no. of
chromosomes is 47

DOWNS SYNDROME
(trisomy 21, monogolism)

Down syndrome
(Karyotype)

normal

abnormal

Monosomy

(reduction in number)

45 chromosomes (only
one X chromosome)

At adolescence, NO
ovulation & menstruation

Short, stunted & sterile.

Web-neck

Ovarian Dysgenesis
(Turner's Syndrome)

Turners Syndrome
(karyotype)

Abnormalities of chromosome
structure.

In many tumors, the affected cells have

constant chromosomal abnormality

IN CHRONIC MYELOID LEUKAEMIA

- translocation between chromosome
9 and 22 leading to formation small
chromosome 22 called
Philadelphia, or Ph, chromosome.

More abnormalities of structure

INVERSION.

Types of genetic disorders

1.

Single gene disorders.

2.

Chromosomal disorders.

3.

Complex multigenic disorders.

COMPLEX MULTIGENIC DISORDERS

Disorder caused by combination of
small variation in genes, with involvement of
environmental factors & lifestyle (also called
multifactorial diseases).
1.

Heart diseases.

2.

Diabetes.

GENETIC TESTING
1.

Biochemical genetic testing - assay for

specific metabolites that indicate a genetic
disease (Galactosemia, Tay Sachs Disease).

2.

Direct genetic testing - examination of DNA to

determine if mutations are present.
(Sickle cell anemia, beta thelassemia).

3. Cytogenetic testing (Downs syndrome).

Down syndrome
(Karyotype)

normal

abnormal

3. Cytogenetic testing - Deletions