3. Mendelian Pedigree patterns Autosomal dominant Autosomal recessive X-Linked recessive X-linked dominant Y-linked

4. Autosomal dominant (3.2A) Marfan’s 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.

7. 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.

10. 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.

13. 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.

16. 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.

19. Mitochondrial diseases Typical pattern for hearing loss. Atypical Leber’s hereditary optic atrophy.

21. Complications to basic pedigrees Typical pattern for blood group O (3.13). AD with nonpenetrance in II2 (3.14). AD with variable expression (3.17). Genetic imprinting (3.18). X-linked dominant incontinentia pigmenti (3.19). X-linked recessive with inbreeding (3.20). A new AD mutation, mimicking recessive (3.21).

22. Complications to basic pedigrees Typical pattern for blood group O (3.13). –Appears as a dominant pattern

23. Complications to basic pedigrees AD with nonpenetrance in II2 (3.14).

24. Complications to basic pedigrees AD with variable expression (3.17). –Waardenburg syndrome –Shading 1st quad = hearing loss –Shading of 2 nd quad = different colored eyes –Shading of 3 rd quad = white forelock –Shading of 4 th quad = premature graying of hair

26. Complications to basic pedigrees Genetic imprinting (3.18). –AD glomus tumors manifest only when gene s inherited from father (A). –AD Beckwith-Wiedemann syndrome manifests only when gene is inherited from mother (B).

28. Complications to basic pedigrees X-linked dominant incontinentia pigmenti (3.19). –Affected males abort spontaneously.

29. Complications to basic pedigrees X-linked recessive with inbreeding (3.20). –Inbreeding gives an affected female and apparent male to male transmission.

31. Complications to basic pedigrees A new AD mutation, mimicking recessive (3.21).

32. 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).

34. 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.

36. Germinal Mosaic AD adenomatous polyposis –Normal = bottom band, mutant = upper bands –Females II 2 and II 3 are carriers of high risk allele. –High risk chromosome is blue, II 2 shows mosaic expression while III 4 does not.

40. Hardy-Weinberg Law p 2 + 2pq + q 2 = 1.0 p + q = 1.0

41. Incidence Autosomal recessive –q 2 Autosomal dominant –p 2 + 2pq

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