Genetic pdf - د. فائزة

Genetic disorders

Dec. 9 . 2015

Genetic disorders

Objectives

• SNP & CNV
•  Types of genetic disorders
• Genes encoding structural pr.
   Marfan Syndrome “MFS”
   Ehlers- Danlos Syndrome “EDSs”
• Genes encoding receptor proteins’ or channels.
   Familial hypercholestremia.

The DNA encodes 30,000 genes

CNV

Single Nucleotide Polymorphism

Copy Number Variation

SNPs are used as genetic markers

to identify genes responsible for
disease susceptibility

or a

particular trait.

SNPs as gene mapping markers

Point mutations



Not all single base pair differences are
SNPs



They can be a mutation if least
abundant allele has

a frequency < 1% in

a population

Causes of gene mutations

Mutation



Gene directly leads to
disorder



Mendelian pattern of
inheritance



Rar

Polymorphism



Gene confers an increased
risk, but does not directly
cause disorder



No clear inheritance pattern



Common in population

CNV

• It was generally thought that genes were almost

always present in

two copies

in a genome.

• However, recent discoveries have revealed that

large segments of DNA ranging in size from
thousands to millions of DNA bases, can vary in
copy-number.

• CNV; affecting a greater fraction of the genome

than single nucleotide polymorphisms (SNPs).

Copy Number Variation (CNV)

• CNV

; is when the number of copies of a

particular gene varies from one individual to
the next.

• The genome experiences

gains and losses

genetic material.

• The extent to which CNV contributes to

human disease is not yet known.

• Some

cancers

are associated with elevated

CNs of particular genes.

Genes are found to be CNV
are;

Genes that are involved in the

immune system

and in

brain

development and activity

–

two functions that have
evolved rapidly in humans

–

tend to be enriched in CNVs.

While, genes that play a role in

early development and cell
division

– both critical to

fundamental biology

– tend to

be spared

Mitochondrial

inheritance

SINGLE GENE DISORDERS

• STRUCTURAL PROTEIN DEFECT

(Marfan, Ehl-Dan)

– Structure
– Function
– Quantity

• RECEPTOR/TRANSPORT PROTEIN DEFECT

(Familial

Hypercholesterolemia)

• ENZYME DEFECT

(Most of them, e.g., PKU)

– Accumulation of substrate
– Lack of product
– Failure to inactivate a protein which causes damage

• ENZYME DEFECT WHICH INCREASES DRUG

SUSCEPTIBILITY:

G6PDPrimaquine

STRUCTURAL PROTEIN DEFECTS

• Marfan Syndrome

– Fibrillin-1 defect.
– Tall, dislocated lens, aortic arch aneurysms, etc.
– Abraham Lincoln?

• Ehlers-Danlos Syndromes (AD, AR)

– Multiple (30?) different types
– Classical, Hypermob., Vasc., KyphoSc., Joints., Derm
– Various collagen defects
– Hyperelastic skin, hyperextensible joints

•

Fibrillin-1

is a major component of

the

microfibrils

that form a sheath

surrounding the amorphous

elastin



Marfan Syndrome

• AD
• Mutation affect fibrillin (Glycopr. In microfibrils

in ECM)

• Aorta, Ligaments, Cilliary zonules (lenses)

Lens dislocation &Marfan”s family

Marfan Syndrome (MFS)

Pectus excavatum and dislocated lens in
marfan syndrome

Marfan syndrome

Aorta Media fragmentation & aneurysm
Valve Incompetence
Mitral Floppy valve, prolaps

Ehlers-Danlos syndrome (EDSs)

(Cutis Laxa)

• Group of dis. (more than 30).
• Single gene diorders (

AD or AR

)

• caused by defect in collagen synthesis or
structure weakness in tissue rich in
collagen.
• considerable increase in skin, joints &
ligament extensibility