Modes of Inheritance

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Modes of Inheritance

• Jonathan Wolfe
• Wolfson House, room 109
• http//www.ucl.ac.uk/ucbhjow/

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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

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Mendels laws

• 0. 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.

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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
• Huntingtons disease, Achondroplastic dysplasia,
  Neurofibromatosis.

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A large autosomal dominant pedigree!
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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

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Autosomal recessive

• Inbreeding increases the chance of observing an
  autosomal recessive condition
• E.g. Cystic fibrosis, sickle cell disease, Tay
  Sachs disease.

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Exceptions to clear cut Mendelian inheritance

• Lethal alleles

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Exceptions to clear cut Mendelian inheritance

• Lethal alleles
• Incomplete dominance

Familial Hypercholesterolemia / normal /-
death as young adult -/- death in childhood
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Exceptions to clear cut Mendelian inheritance

• Lethal alleles
• Incomplete dominance
• Codominance
• Silent alleles

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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.
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Exceptions to clear cut Mendelian inheritance

• Lethal alleles
• Incomplete dominance
• Codominance
• Silent alleles
• Epistasis

• Pleiotropy
• genetic heterogeneity

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Exceptions to clear cut Mendelian inheritance

• Lethal alleles
• Incomplete dominance
• Codominance
• Silent alleles
• Epistasis
• Pleiotropy
• genetic heterogeneity

• variable expressivity
• incomplete penetrance

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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
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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

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Mitochondrial inheritance
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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
• Incomplete ascertainment
• mitochondrial inheritance
• uniparental disomy
• linkage