Mendelian Pedigree patterns

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Mendelian Pedigree patterns

• Autosomal dominant
• Autosomal recessive
• X-Linked recessive
• X-linked dominant
• Y-linked

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Autosomal dominant (3.2A)

• Marfans syndrome, Neurofibromatosis, Huntington
  Disease, Retinoblastoma
• An affected person usually has at least one
  affected parent.
• Affects either sex.
• Transmitted by either sex.
• A child of affected x unaffected mating has a 50
  chance of being affected.

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Autosomal recessive (3.2B)

• Cystic fibrosis, Phenylketonuria, Tay-Sachs
• Affected people are usually born to unaffected
  parents.
• Parents of affected people usually asymptomatic
  carriers.
• There is an increased incidence of parental
  consanguinity.
• Affects either sex.
• After birth of an affected child each subsequent
  child has 25 chance of being affected.

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X-linked recessive (3.2C)

• Hemophilia, Lesch-Nyhan
• Affects mainly males.
• Affected males are usually born to unaffected
  parents the mother is typically an asymptomatic
  carrier and may have affected male relatives.
• Females may be affected if father is affected and
  mother is a carrier.
• No male to male transmission.

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X-linked dominant (3.2D)

• Vitamin D resistant rickets.
• Affects either sex, but more females than males.
• Females are often more mildly and more variably
  affected than males.
• The child of an affected female, regardless of
  sex, has a 50 chance of being affected.
• For an affected male, all daughters and no sons
  are affected.

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Y-linked inheritance (3.2E)

• Affects only males.
• Affected males always have an affected father
  unless there is a new mutation.
• All sons of an affected man are affected.

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Mitochondrial diseases

• Typical pattern for hearing loss.
• Atypical Lebers hereditary optic atrophy.

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Complications to basic pedigrees

• Typical pattern for blood group O (A).
• AD with nonpenetrance in II2 (B).
• AD with variable expression (C).
• Genetic imprinting (D and E).
• X-linked dominant incontinentia pigmenti (F).
• X-linked recessive with inbreeding (G).
• A new AD mutation, mimicking recessive (H).

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Complications to basic pedigrees

• Typical pattern for blood group O (A).
• Appears as a dominant pattern

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Complications to basic pedigrees

• AD with nonpenetrance in II2 (B).

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Complications to basic pedigrees

• AD with variable expression (C).
• Waardenburg syndrome
• Shading 1st quad hearing loss
• Shading of 2nd quad different colored eyes
• Shading of 3rd quad white forelock
• Shading of 4th quad premature graying of hair

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Complications to basic pedigrees

• Genetic imprinting (D and E).
• AD glomus tumors manifest only when gene s
  inherited from father (D).
• AD Beckwith-Wiedemann syndrome manifests only
  when gene is inherited from mother (E).

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Complications to basic pedigrees

• X-linked dominant incontinentia pigmenti (F).
• Affected males abort spontaneously.

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Complications to basic pedigrees

• X-linked recessive with inbreeding (G).
• Inbreeding gives an affected female and apparent
  male to male transmission.

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Complications to basic pedigrees

• A new AD mutation, mimicking recessive (H).

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Huntington Age of Onset

• Probability that an individual carrying the
  disease gene will have developed symptoms by a
  given age (A).
• Risk that a healthy child of an affected parent
  carries the disease gene at a given age (B).

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New Mutation in X-linked recessive DMD

• III1 has the grandparental X which acquired a
  mutation at some point.
• III1 caries a new mutation
• II1 is a germinal mosaic (risk for children, but
  not sisters)
• II1 was the result of a single mutation, standard
  recurrence risk or X-linked recessives, sister
  free of risk.
• I1 was a germinal mosaic, all the sisters have a
  significant risk, which is hard to quantify.

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Germinal Mosaic

• AD osteogenesis imperfecta
• Normal 63bp band, mutant 72bp band
• Both affected sons are heterozygous.
• Fathers blood is normal (A lane 5) with sperm
  abnormal (A lane 10).
• Tissue specific mosaicism (B).

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Hardy-Weinberg Law

• p2 2pq q2 1.0
• p q 1.0

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Incidence

• Autosomal recessive
• q2
• Autosomal dominant
• p2 2pq

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