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

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