Non Mendelian Inheritance

Dr Heba Kassem (Ph.D., M.D.)

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Non Mendelian Inheritance

Mitochondrial inheritance Unstable or Expanding mutations Multifactorial inheritance

Mitochondrial Inheritance
It is transmitted only through females to both sex (pedigree) The proportion of affected offspring is variable Examples: Lebers optic atrophy, Deafness, poorly classified CNS degenerative diseases

Pedigree of Mitochondrial inheritance

Figure 7-34 Pedigree of Leber hereditary optic neuropathy, a form of spontaneous blindness caused by a defect in mitochondrial DNA. Inheritance is only through the maternal lineage, in agreement with the known maternal inheritance of mitochondrial DNA. No affected male transmits the disease.

Downloaded from: StudentConsult (on 22 January 2010 09:44 PM) 2005 Elsevier

Mitochondrial inheritance

Unstable or Expanding mutation (Dynamic)

These are tandem repeats that often change size on transmission to children (usually trinucleotide repeats) Fragile X Syd (CGG repeats)

Normally they are 50, premutation is 50200 (normal phenotype but transmit the trait), >200 is the full mutation. The severity correlates with the size of the repeat.

Fragile X (Molecular testing)

Triplet expansion Huntingtons Disease (CAG)

Triplet expansion of Myotonic Dystrophy

10Kb 9Kb

Multifactorial /Polygenic Disorders

They are caused by multiple genes at more than one locus with environmental contribution. The sum of these determine the individual susceptibility Common disorders: DM, CV diseases, congenital malformation and cancer

Multifactorical Inheritance
Increased risk to relatives

Multiple family members Proband is of a rarely affected sex Close relationship to proband Severe or early onset in the proband The incidence in close relatives is around 2-4%

Genetic susceptibility
Single nucleotide polymorphism (SNP)
AGCCTGTCACT AGCCTATCACT
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Ethical issues in medical genetics

Genetics affect the whole family and the society in general not just the individual Genetic counselling is not directive, non judgemental communication Informed consent before genetic testing (predictive) Confidentiality Examples of ethical dilemmas