HUMAN GENETICS

1. HUMAN GENETICS Disorders

2. Interpreting Pedigrees with Andrew Douch • Interpreting Pedigrees the Fast Way –Example 1(6:42) • Example 2 (6:46) • 1. Is anyone with a phenotype different from parents? • 2.Are there any girls with recessive phenotype who have a father or son with a dominant phenotype? • Autosomal Dominant X-linked dominant • Autosomal Recessive X-linked recessive

3. Autosomal Dominant:trait does not skip generations

4. Autosomal Recessive: tends to skip generations

5. X-linked dominant: both males and females affecteddoes not skip generations • Affected sons have an affected mother

6. X-linked recessive: more males than females affected • Skips generations: affected sons from non-affected mothers

7. Testing for genetic disorders • Ultrasound imaging-a sonogram made from passing high-frequency sound waves with a transducer through the abdomen • (least invasive)

8. Testing for genetic disorders • Amniocentesis-a small amount of amniotic fluid, which contains fetal tissues, is sampled • Use cells for karyotyping

9. Testing for genetic disorders • Chorionic villus sampling (CVS)-take a sample of the placental tissue for chromosomal abnormalities • Can use cells for karyotyping

10. AUTOSOMAL RECESSIVE • Autosomes = , chromosomes #1- #22

11. It causes the body to produce a thick,sticky mucus that clogs the lungs and digestive tract. Cystic Fibrosis-ff On Chromosome 7 Autosomal recessive

12. One test is for salty skinCF salt test • Salty skin (Mutations of the CFTR gene affect functioning of the chloride ion channels) • thin (do not digest well) • abnormal bowel movements • CFTR video (8:18) describe 6 mutation disfunctions for 2 pts Ex Cr

13. Cystic Fibrosis (cont.) • Most common fatal genetic disease in US today • Most common in Caucasians • Small Child CR Treatment (thumping) • Thumping Vest (1:24) • Living with CF (3:48) Daily meds

14. Chromosome 7 FF = no CF Ff = carrier ff = has CF (recessive) Life with CF (3:48) Cystic Fibrosis

15. PKU • Phenylketonuria (PKU)

16. Lacks enzyme to break down the amino acid phenylalanine (found in milk) PKU on chromosome 12recessive

17. PKU (cont.) • The breakdown products can be harmful to developing nervous systems • Leads to mental retardation. • Kate with PKU Movie

18. Chromosome 12 Put on low protein diet Avoid phenylalanine PKU

19. Results in degeneration of the nervous system. Chromosome 15 recessive Highest rate in Eastern European Jews, next Irish-Americans TAY SACHS

20. Tay Sachs (cont) • Lack enzyme to break down fat, accumulates in brain (poisons it) • tt • Chromosome 15 • NOVA Online | Cracking the Code of Life | Watch the Program Here #3

21. Tay Sachs Disease is a fatal lipid storage disorder where a fatty substance (ganglioside) builds up in the nerve tissue and cells of the brain. This is caused by an insufficient enzyme called beta-hexosaminidase A that catalyzes the biodegration of gangliosides.

22. Tay-Sachs Symptoms Symptoms first appear at 4 to 6 months of age when an apparently healthy baby gradually stops smiling, crawling or turning over, loses its ability to grasp or reach out, and eventually becomes blind, paralyzed and unaware of its surroundings. Death usually occurs by age 4. Tay-Sachs PT (1:52)

23. Inability to manufacture pigments (melanin) in skin and eyes Autosomal recessive trait Chromosome 11 Albinism

24. Albinism

25. Famous Albinos • Andy Warhol, a famous artist “The Twins” in Matrix Reloaded Rock musician Edgar Winter, an albino.

26. Is this an advantage or disadvantage?

27. Different kinds of albinism • affect chromosomes 1, 9, 10, 11, 15 and X (ocular albinism) Often rapid back and forth eye movement – lack of pigment in eyes.

28. Polar bears actually have black skin under all that white fur.

29. AUTOSOMAL DOMINANTon chromosomes 1-22

30. Autosomal dominant disease Chromosome #11 Red blood cells collapse and clot blood vessels Found in African-Americans Sickle Cell Anemia

31. Normal Red Blood Cells-like a donut Sickle-cells collapse, hard, clog vessels Sickle-Cells

32. Sickle-Cell Anemia • Codominant • SS = disease • AS = carrier (somewhat resistant to malaria) • AA =normal hemoglobin • Living with SSA Plasmodium in blood - malaria

33. Sickle-Cell Complications 1.pain episodes 2.strokes 3.increased infections 4.leg ulcers 5.bone damage 6.yellow eyes or jaundice 7.early gallstones 8.lung blockage 9.kidney damage and loss of body water in urine 10.painful erections in men (priapism) 11.blood blockage in the spleen or liver (sequestration) 12.eye damage 13.low red blood cell counts (anemia) 14.delayed growth

34. Woody Guthrie’s disease (folksinger 1960’s) Autosomal dominant Does not manifest itself until age 20’s - 30’s H=dominant disease Huntington’s Disease

35. What is the chance of a child of a Huntington Mother having Hungtingtons?

36. Chromosome 4 Atrophy of brain Uncontrollable muscle spasms 40+ CAG’s (build up protein clumps) Huntington's Chorea Dance (5:33) Huntington’s Controls thinking, emotion, movement

37. Huntington’s • Clumsiness • Jaw clenching • Loss of coordination and balance • Slurred speech • Swallowing and/or eating difficulty • Uncontrolled continual muscular contractions • Walking difficulty, stumbling • Hostility/irritabilityInability to take pleasure in life • Lack of energy • person with Huntington's also may exhibit psychotic behavior: • Delusion • Halluciations • Inappropriate behavior (e.g., unprovoked aggression) • Paranoia

38. Achondroplasia -Autosomal Dominant -chromosome 4 Achondroplasia: Genetic Causes (2:40)

39. Achondroplasia • Dwarfism • Achondroplasia: Genetics (2:20) • short stature • Dwarfism • shortening of limbs, • trident hands • prominent forehead • Average adult male height of 52 inches; average adult female height of 49 inches

41. FAQ • Can short-statured couples become the parents of average-size children? • AA=dead • Aa=Achondroplasia • aa=normal A a A a

42. FAQ • Can short-statured couples become the parents of average-size children? • AA=dead • Aa=Achondroplasia • aa=normal A a A a X

43. Alzheimer syndrome • Widespread nerve cell dysfunction and cell death in the brain • Dementia (memory loss) • Alzheimer's Disease: Medical Update (1:39) • Life with Alzheimers (3:56)

44. Alzheimer Syndrome • Autosomal Dominant • Found on Chromosome 1, or 10, or 14, or 19, or 21 • APO4, is a cholesterol-carrying protein linked to development a protein that forms plaque in the brain • Alzheimer's neurology (1:01) • Alzheimers' Disease: Neurology

45. Brain Loss

46. Early or mild stage: • memory loss, especially of recent events • difficulty in recalling names and conversations • misplacing objects  • becoming lost in familiar neighborhoods • repeating stories and conversations • difficulty in learning new information • personality changes • decreased motivation and drive • easily upset or anxious 

47. Marfan Syndrome • autosomal dominant disorder • chromosome 15

48. Marfan’s: taller, pigeon chest Marfan's Video (2:45) Spidery fingers, enlargement of aorta

49. Michael Phelps Does Not Have Marfans X Extra Tall Athletes in their recruiting physical are tested for Marfans. Clarence Holloway of Louisville does have Marfan's syndrome (had open-heart surgery) ManuteBol did Died at age 47 Gheorge Muresan 7’7”

50. Marfan Syndrome • a connective tissue disorder • Affects skeleton, lungs, eyes, heart and blood vessels. • unusually long limbs • High arch palate • Debated if Abraham Lincoln has Marfan’s.