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 CTG
repeats
5
phenotype
19 - 30
premutant
50 - 100
mildly affected
2,000 or more
severely affected
normal
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