Genetics: Analyzing Pedigrees & Inheritance

Analyzing Pedigrees

• Mendelian concepts of dominance and segregation studied in humans through pedigree charts.
• Pedigree charts use symbols to represent males, females, marriages, identical twins, fraternal twins, consanguineous marriages, affected and unaffected individuals, carriers, deceased individuals, and unknown sex.
• Roman numerals symbolize generations.
• Arabic numbers symbolize individuals within a given generation.
• Birth order within each group of offspring goes from left to right.
• Autosomal recessive inheritance is illustrated via a pedigree example.

Patterns of Inheritance

• Inheritance patterns include autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and Y-linked.

Autosome Linked Dominant Traits

• Transmission of traits occurs from parents of either sex.
• Males and females are equally affected.
• The pedigree is vertical, meaning the trait is present in each generation.
• Multiple generations are typically affected.
• If A is the dominant allele and a is the recessive allele, then individuals who are AA or Aa are affected.
• Unaffected individuals are aa.

Autosome Linked Dominant Examples

• Achondroplasia causes dwarfism, large head, and short extremities.
• Marfan syndrome causes long, thin extremities and fingers, with eye and cardiovascular problems.
• Von Hippel-Lindau condition can have onset in adolescence or adulthood; it may cause hemangioblastomas, retinal angiomas, or kidney/pancreatic tumors.

Autosomal Recessive Traits

• Occur in equal proportions in multiple male and female siblings with normal carrier parents.
• Siblings are homozygous for a defective allele, while parents are heterozygous carriers.
• Consanguinity (marriage between relatives) may lead to the traits sometimes.

Autosomal Recessive Traits - Alleles

• If A is normal/dominant and a is mutant/recessive, affected individuals are aa.
• Carriers are Aa, and unaffected individuals are AA.

Autosomal Recessive Trait Examples

• Sickle cell anemia affects red blood cells, leading to pain, infections, and other issues.
• Cystic fibrosis causes thick, sticky mucus to build up in the lungs, digestive system, and other organs leading to respiratory issues and digestive complications.
• Tay-Sachs disease causes a neurological disorder from the absence of a specific enzyme that breaks down fatty substances leading to nerve damage and progressive disability.

X-Linked Dominant Traits

• The trait appears in almost all generations, with vertical inheritance.
• If the female is affected (XDXd / XDXD), about half of her sons are affected.
• If the male is affected, all his daughters would be affected, but none of his sons are.
• The pedigree resembles the pattern of autosomal dominants, except there is no male-to-male.
• If X^ is the affected/dominant X and Xª is the normal/recessive X, affected males are X^Y.
• Unaffected females are XªXª.
• Affected females are X^Xª or X^X^.

X-Linked Dominant Trait Examples

• Incontinentia pigmenti causes a “marble-cake-like” appearance on the skin, as well as problems with the eyes, teeth, nails, and hair.
• Alport syndrome is a hereditary disease that affects the eyes, kidneys, and cochlea; some females may have very few signs of the disease.

X-Linked Recessive Traits

• Females express the trait only when homozygous for the recessive mutant allele (XrXr), whereas males do so even when they are hemizygous (XrY).

X-Linked Recessive Trait Examples

• Red-green color blindness: common, and affects more men than women.
• Hemophilia A: a bleeding disorder resulting from a mutation in the factor VIII gene.
• Duchenne muscular dystrophy: causes muscle weakness leading to respiratory failure and death.

Y-Chromosome Linked Traits

• Any trait on the Y-chromosome must be present in males only, and not in any females.

Y-Chromosome Linked Inheritance

• If Y^ is mutant/affected and Y is normal, affected males are XYA.
• Unaffected males are XY.

Y-Chromosome Linked Example

• Hypertrichosis of the ear (hairy ears) is one common example.
• Webbed toes are a condition with a web-like connection between the second and third toes.
• Y-linked infertility: Conditions like azoospermia (absence of sperm) or oligospermia (low sperm count).
• Porcupine man (ichthyosis hystrix) is a condition with thickening of the skin, that gradually becomes darker, scaly, rough, and with bristle-like outgrowths.