MENDELIAN INHERITANCE 2002

1. MENDELIAN INHERITANCE 2002 • Genotype • Phenotype • Locus • Allele • Homozygote/ Heterozygote • Compound heterozygote • Proband

2. AD • AR • XLR • XLD • Not genetic

3. Mozart’s Piano Concerto in A-major is Köchel number • A K365 • B K450 • C K482 • D K488 • E K491

4. Clinical vignette • S G: 20 yo college student • Spontaneous rupture of the common iliac artery • Friable tissues, extensive bleeding • Past history: • Easy bruising • Lax joints (fingers, elbows, left shoulder) • D G: 53 yo mother of SG • Spontaneous perforation of the sigmoid colon • Past history • Easy bruising • No joint laxity • Two normal pregnancies

5. Laboratory analysis • Skin fibroblasts: abnormal type III collagen • COL3A1 DNA analysis: Gly25Val • Diagnosis: Ehlers-Danlos Syndrome, Type IV

6. Pedigree symbols

8. Autosomal dominant inheritance • Vertical • Males and females affected • Males and females transmit • Each affected has one affected parent…

10. NF1 Neurofibroma Café-au-lait

11. Lisch Nodules

12. Neurofibromatosis 1variable expressivity • Café-au-lait spots • Axillary freckling • Lisch nodules • Cutaneous neurofibromas • Plexiform neurofibromas • Scoliosis • CNS tumors

13. Marfan syndrome

14. Marfan ectopia lentis

15. Marfan life expectancy

16. Marfan Syndrome variable expressivity

17. Incomplete penetrance AD Erythermalgia

18. Achondroplasia

19. What is the risk that this couple’s child will have achondroplasia ? • A ¼ • B ½ • C ¾ • D 1 • E 0

21. Achondroplasia mutations in FGFR3

22. Allelic Heterogeneity COL3A1 (EDS IV)

23. Autosomal Recessive

24. Autosomal Recessive • Horizontal • Males and females affected • Parents of affected are normal

27. Autosomal recessive

28. AD • AR • XLR • XLD • Not genetic

30. Locus Heterogeneity congenital deafness IV-1,2,3,4,5,6 are all double heterozygotes

31. X-linked recessive

32. X-linked recessive inheritance • “Diagonal” • Males affected… • Transmitted by carrier females • NO male-to-male transmission • Daughters of affected males are obligate carriers

33. X-linked recessiveinheritance

34. X-linked dominant

35. X-linked NOT sex-linked

36. Mitochondrial inheritance • Mitochondrial DNA • 2 to 100 mitochondria/cell • 5 to 10 chromosomes/mitochondrium • 16.5 kb mt DNA • 37 genes • Mitochondrial inheritance • Maternal • Heteroplasmy

37. MERRF

38. MERRF Pedigree

39. Heteroplasmy

40. Myotonic Muscular Dystrophy • Most common inherited muscular dystrophy of adults • Muscle wasting—face, neck, distal muscles • Myotonia • Cardiac and smooth muscle affected • Cataracts • Immunoglobulin abnormalities • Insulin resistance • Occ. Mild MR

45. Autosomal dominant ANTICIPATION

46. DENIAL AIN’T JUST A RIVER IN EGYPT -Rap song

47. The absence of evidence is NOT equivalent to evidence of absence

48. Triplet (CTG) Repeats

49. Repeat Expansion

50. Triplet Repeat Diseases