Modes of Inheritance
Jonathan Wolfe
Wolfson House, room 109
http://www.ucl.ac.uk/~ucbhjow/
Objectives - at the end of this
lecture you should be able to:
• Identify dominant and recessive Mendelian
modes of inheritance
• Describe reasons why some genetic diseases
seem to depart from Mendelian expectations
Mendel’s laws
0.
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Genes are particulate and come in different forms known as alleles.
Organisms (peas or humans!) have two copies of each gene but transmit only
one to each offspring. Which one is transmitted is chosen at random. i.e. if
you are heterozygous for two different alleles, the alleles will segregate from
each other in your offspring.
Where alleles of more than one gene are segregating, segregation at each
gene occurs independently of the others.
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
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Lethal alleles
Incomplete dominance
Codominance
Silent alleles
Exceptions to clear cut Mendelian
inheritance
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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
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Lethal alleles
Incomplete dominance
Codominance
Silent alleles
Epistasis
Pleiotropy
genetic heterogeneity
Exceptions to clear cut Mendelian
inheritance
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•
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Lethal alleles
Incomplete dominance
Codominance
Silent alleles
Epistasis
Pleiotropy
genetic heterogeneity
• variable expressivity
• incomplete penetrance
Exceptions to clear cut Mendelian
inheritance
•
•
•
•
•
•
•
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•
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
• germline mosaicism
• phenocopies
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•
•
•
Incomplete ascertainment
mitochondrial inheritance
uniparental disomy
linkage