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Ethology of diseases
For any condition, the over all balance of genetic and
environmental determinants can be represented by a
point somewhere within the triangle.
Continuum of Penetrance
There is a Continuum of Penetrance from fully
penetrant conditions, where other genes and
environmental factors have no effect, through to low-
penetrance genes that simply play a small part, along
with other genetic and environmental factors, in
determining a persons susceptibility to a diseases.
Classification of Genetic Disorders
Multifactorial and polygenic

Single gene (Mendelian)


Somatic Mutations (cancer)

Multifactorial and Polygenic
Associated with the effects of multiple genes in
combination with lifestyle and environmental factors.

There is no clear cut patter of inheritance.

On a pedigree, polygenetic disorders do tend to run in

families", but the inheritance does not fit simple pattern
as the Mendelian diseases.

E.g. Gout, Heat diseases, Hypertension, Diabetes,

Single gene (Mendelian)
The result of a single mutated gene that can be pass
on to subsequent generation

Subclasses of single gene disorders:

Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
Autosomal dominant
Only one mutated copy of the gene is needed for a
person to be affect by an Autosomal dominant disorder.

Each affected person usually have one affected parent.

Low penetrance

E.g. Huntingtons disease, Marfan syndrome

Autosomal Recessive
Two copies of the gene must be mutated for the
person to be affected

An affected person usually has unaffected parents

who each carry a single copy of the mutated gene.

E.g. E.g. Cystic fibrosis, Sickle cell anemia, Tay-

Sachs disease,
X-linked dominant
Mutations in genes on the X chromosome

Males are more frequently affected than female.

A woman with an Xlinked dominant disorder has a

50% chance of having an affected daughter or son.

E.g Hypophosphatemia, Aicardi Syndrome,

Aicardi Syndrome
Xlinked recessive
Xlinked recessive disorders are also caused by
mutations in genes on the X chromosome.
Males are more frequently affected than females
The sons of a man with an Xlinked recessive disorder
will not be affected, and his daughters will carry one
copy of the mutated gene.
With each pregnancy, a woman who carries an Xlinked
recessive disorder has a 50% chance of having sons
who are affected and a 50% chance of having
daughters who carry one copy of the mutated gene.
E.g Hemophilia A, Color blindness, Muscular
Ylinked disorders
Ylinked disorders are caused by mutations on the Y

Only males can be affected.

E.g. Male Infertility

Mitochondrial Inheritance

Also known as maternal inheritance

Only females can pass on mitochondrial conditions to

their children.

E.g. Leber's Hereditary Optic Neuropathy (LHON)

Chromosomal disorders
These may be from alterations in the number or structure of
the chromosomes and may affect autosomes or sex

The major chromosomal disorders are associated with

cardiovascular disorders lead primarily to congenital heart

Aneuploidy is the most common and clinical significant type

of chromosomal disorder.

Exits when an entire chromosome is missing or when there is

an extra chromosome.
Abnormalities of chromosome structure involves
chromosomal rearrangement caused by chromosome
breakage followed by reconstitution in an abnormal form.

Fragile X chromosome- Characterized by mental
retardation and an inducible cytogenetic abnormality in
the X chromosome.

Other disorders include Downs Syndrome in which the

number of chromosomes is increased by a third 21st
chromosome and hence a total of 47 chromosomes
Somatic mutation
Occur in non-germ line tissues.


Mutation (by environmental mutagens or as

consequence of normal cellular metabolism or by
spontaneous errors in DNA replication and repair) in
genes results in altered proteins.
The Human genome
Gene structure and function
First, many genes are capable of generating multiple
different proteins, not just one.
Second, individual proteins do not function by
Most human genes are unique single-copy genes
coding for polypeptides that are involved in or carry
out a variety of cellular functions.
Many genes have similar functions, making up what
are known as multigene families.
Some are found physically close together in clusters,
for example the - and -globin gene clusters on
chromosomes l6 and 11.
Classic gene families include the numerous copies of
genes coding for the various ribosomal RNAs e.g.
transfer RNAs.
Gene super families include the HLA (human
leukocyte antigen) genes on chromosome 6 and the T-
cell receptor genes, which have structural homology
with the immunoglobulin (Ig) genes.
Pseudogenes are genes that closely resemble known
structural genes but which, in general, are not
Gene Organization and Structure
Fundamental of Gene Expression
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