Genetic Disorders

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Genetic Disorders
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• Disorders with Multifactorial Inheritance
• Environmental influences two or more mutant
  genes having additive effects
• Genetic component exerts a dosage effect -the
  greater the number of inherited deleterious
  genes, the more severe the expression of the
  disease
• Polygenic inheritance should not be used (because
  of significant role of environmental factors)
• Normal phenotypic characteristics governed by
  multifactorial inheritance
• Hair color, eye color, skin color, height, and
  intelligence

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• Disorders with Multifactorial Inheritance
• Characterized by
• 1.Risk of expressing a multifactorial disorder is
  conditioned by the number of mutant genes
  inherited
• -risk of cleft lip in the siblings of an index
  case is
• 2.5 if the cleft lip is unilateral but
• 6 if it is bilateral
• 2. Greater the number of affected relatives, the
  higher is the risk for other relatives
• 3. Rate of recurrence of the disorder (in the
  range of 2 to 7) same for all first degree
  relatives
• 4. Both identical twins will be affected is
  significantly less than 100 (range of 20 to
  40)
• 5. Risk of recurrence of the phenotypic
  abnormality in subsequent pregnancies
• Depends on outcome in previous pregnancies
• If one child is affected- up to a 7
• After two affected siblings-the risk is 9.

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Multifactorial Disorders
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• Disorders with Multifactorial Inheritance
• Assigning a disease as Multifactorial Disorders
  depends on
• Factors
• First on familial clustering
• Exclusion of Mendelian and chromosomal modes of
  transmission
• Difficult to distinguish between Mendelian and
  multifactorial inheritance
• Disorders associated with defects in proteins
  that regulate cell growth
• Cancer-causing mutations
• 95 ?affect somatic cells and hence are not
  passed in the germ line
• 5 ? affect germ line (familial cancers )
• Most are AD (few -recessive )