Mendelian Pedigree patterns

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 2nd quad = different colored eyes • Shading of 3rd quad = white forelock • Shading of 4th 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 II2 and II3 are carriers of high risk allele. • High risk chromosome is blue, II2 shows mosaic expression while III4 does not.

40. Hardy-Weinberg Law • p2 + 2pq + q2 = 1.0 • p + q = 1.0

41. Incidence • Autosomal recessive • q2 • Autosomal dominant • p2 + 2pq