Autosomal dominant inheritance

• All affected individuals should have an affected parent

• Both sexes should be equally affected

• Roughly 50% of the offspring of an affected individual should also be affected

• Huntington’s disease, Achondroplastic dysplasia, Neurofibromatosis.

A large autosomal dominant pedigree!

Autosomal Recessive Inheritance

• Usually there is no previous family history• The most likely place to find a second affected

child is a sibling of the first

Autosomal recessive

• Inbreeding increases the chance of observing an autosomal recessive condition

• E.g. Cystic fibrosis, sickle cell disease, Tay Sachs disease.

Exceptions to clear cut Mendelian inheritance

• Lethal alleles

T/+ x T/+

T/T T/+ +/+ 1 : 2 : 1 ratio at conception

0 : 2 : 1 ratio at birth

Exceptions to clear cut Mendelian inheritance

• Lethal alleles

• Incomplete dominance

Familial Hypercholesterolemia

+/+ = normal

+/- = death as young adult

-/- = death in childhood

Exceptions to clear cut Mendelian inheritance

• Lethal alleles

• Incomplete dominance

• Codominance

• Silent alleles

Exceptions to clear cut Mendelian inheritance

• Lethal alleles

• Incomplete dominance

• Codominance

• Silent alleles

• Epistasis The Bombay Phenotype:

The ABO blood group genotype cannot be deduced in h/h homozygotes.

Exceptions to clear cut Mendelian inheritance

• Lethal alleles

• Incomplete dominance

• Codominance

• Silent alleles

• Epistasis

• Pleiotropy

• genetic heterogeneity

Exceptions to clear cut Mendelian inheritance

• Lethal alleles

• Incomplete dominance

• Codominance

• Silent alleles

• Epistasis

• Pleiotropy

• genetic heterogeneity

• variable expressivity

• incomplete penetrance

Exceptions to clear cut Mendelian inheritance

• Lethal alleles

• Incomplete dominance

• Codominance

• Silent alleles

• Epistasis

• Pleiotropy

• genetic heterogeneity

• variable expressivity

• incomplete penetrance

• Anticipation

E.g. Myotonic dystrophy

Number of CTGrepeats

phenotype

5 normal

19 - 30 premutant

50 - 100 mildly affected

2,000 or more severely affected

Exceptions to clear cut Mendelian inheritance

• Lethal alleles

• Incomplete dominance

• Codominance

• Silent alleles

• Epistasis

• Pleiotropy

• genetic heterogeneity

• variable expressivity

• incomplete penetrance

• Anticipation

• germline mosaicism

• phenocopies

Phocomelia

• Incomplete ascertainment

• mitochondrial inheritance

Mitochondrial inheritance

Exceptions to clear cut Mendelian inheritance

• Lethal alleles

• Incomplete dominance

• Codominance

• Silent alleles

• Epistasis

• Pleiotropy

• Genetic heterogeneity

• Variable expressivity

• Incomplete penetrance

• Anticipation

• Reverse anticipation

• Germline mosaicism

• Phenocopies

• Mitochondrial inheritance

• Uniparental disomy

• Linkage