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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