Genetics

GeneticsDr.Shatha Th.Ahmed

Lec 2

Autosomal Recessive Disorders

• They represent the largest group of Mendelian disorders.
• Appear only when both alleles have the same gene mutation (i.e. manifested in the homozygous state).
• Both parents are usually heterozygous but are phenotypically normal (asymptomatic heterozygous or carriers).
• Siblings of carrier parents have the chance of one in four to be affected.
• Usually increased in the marriage between relatives.Onset is frequently early in life.
• The expression is mostly uniform.
• Complete penetrance is common.
• New mutation is rare.
• In many cases enzymes are affected





Examples of Autosomal Recessive Disorders
Sickle cell anemia
cystic fibrosis
juvenile polycystic kidney disease,
phenylketonuria, glycogen storage diseases
galactosemia
α-1 antitrypsin deficiency
Hemochromatosis
Thalassemia
Lysosomal storage diseases…etc

Sex -Linked Disorders

• Almost all these disorders are X-linked.
• The only Y-linked disorder is the hairy ears.
• Most of the X-linked disorders are X-linked recessive.
• The only X-linked dominant disorders are vitamin D-resistant rickets and Alport's syndrome (Hereditary glomerulonephritis with nerve deafness)

Features of X-linked Disorders

• Females are carriers & males are affected.
• The carrier females transmit the disorder only to their sons which have the chance of 50% to be affected.
• The affected male cannot transmit the disease to sons, but all the daughters are carriers.


• Heterozygous females rarely express the disease except when there is
• Inactivation of the other X-chromosome.
• Father is affected & mother is a carrier.
• Female has one affected X-chromosome as in Turner syndrome.

Examples of X-linked recessive disorders;

Duchenne muscular dystrophy, hemophilias, G6PD and red-green colour blindness, Hemophilia A and B, Hunter syndrome, Fragile Fragile X syndrome.

Mechanisms of Single Gene Disorders

• Enzyme defects and their consequences
• Defects in membrane receptors and transport systems
• Alterations in structure, function, or quantity of non enenzyme proteins
• Mutations resulting in unusual reactions to drugs

Marfan syndrome:

Autosomal dominant disorder of connective tissue that affects fibrillin 1 (a glycoprotein that is secreted by fibroblast) encoded by FBN1 gene (mapped on chr.15).

Prevalence, 3 per 10 000 & 75% are familial.

Fibrillin 1 is a scaffold for deposition of elastin. Its mutation leads to multiple systemic effects.

The main 3 systems affected are the skeleton, eye & cardiovascular system.

Diseases caused by mutations in non-enzymatic structural proteins





Skeletal abnormalities include long legs, arms & fingers, hyperextensibility of joints, depressed sternum

Ocular changes are bilateral subluxation of the lens

CVS abnormalities are aortic aneurysm, aortic incompetence, floppy mitral valve & heart failure
Morphology of Marfan Syndrome