Human Genetic Disorders

1. Human Genetic Disorders

2. Autosomal Recessive Disorders Requires the inheritance of two recessive alleles Error found on chromosomes 1 - 22

3. Albinism • Inability to make melanin which gives pigmentation to hair, eyes, and skin • Mutation in the tyrosinase gene on chromosome #11 • Tyrosinase is an enzyme that functions in the production of melanin

4. Problems • Visual Problems that cannot be corrected with glasses • Sunburn VERY easily • Life expectancy is normal

5. Cystic Fibrosis • Results in thick, sticky secretions in the respiration and digestive tract • Mutation in the gene for the transmembrane protein that acts as a channel for chloride ions • This gene is located on chromosome #7

6. Cystic Fibrosis • 3,200 white babies born each year with CF • 30,000 Americans live with CF • 12 million Americans are carriers • 1/20 European Americans are carriers

7. Cystic Fibrosis & Cholera • Cholera produces a toxin that opens chloride channels in the small intestine. This causes the often fatal diarrhea and dehydration in cholera patients. • In Europe, cholera epidemics have claimed millions of lives • People heterozygous for CF have fewer chloride channels and are resistant to cholera. • This explains the prevalence in European Americans

9. Phenylketonuria (PKU) • One of the most common causes of mental retardation • Mutation in gene for the enzyme phenylalanine hydroxylase on chromosome #12 • This enzyme converts the amino acid phenylalanine to the amino acid tyrosine

10. Phenylketonuria (PKU) • If phenylalanine is not broken down, the build up of this amino acid causes brain dysfunction and mental retardation • All babies in the US are screen for PKU and if put on a phenylalanine restricted diet will not develop mental retardation. • 1 in 4,500 people from Ireland have PKU • 1 in 8,000 American Caucasians have PKU

11. Sickle Cell Anemia • A blood disorder that results in a change in shape of the red blood cell from round to “sickle” shaped. This causes clogging of capillaries and tissues are deprived of oxygen. • Mutation in the beta chain of the hemoglobin protein gene found on chromosome #11.

12. Sickle Cell Anemia • Most prevalent in persons of African descent. • 1/12 African Americans are carriers of the disease. • Heterozygotes have protection from malaria.

14. Tay Sach’s Disease • A fatal disease that results from the build up of fatty acids around nerves of the central nervous system (brain & spinal cord) • Caused by the lack of the enzyme hexosaminidase A which is responsible for degrading lipids (fats) • The gene for this protein is located on chromosome #15

15. Problems • Babies appear normal at first. After a few months they develop developmental problems, go blind, deaf, and become paralyzed. • They are diagnosed by a “cherry-red” spot in the eye • They die by the age of five.

16. Prevalence • Tay-Sachs is most common in descendents of Central & Eastern European Jews • About 1/30 American Jews are carriers of Tay-Sachs disease

17. Autosomal Dominant Disorders Require the inheritance of only one copy of the allele Found on chromosomes 1 - 22

18. Achondroplasia • The most common form of dwarfism • Caused by a mutation in the gene for the Fibroblast growth factor receptor 3 protein • This protein functions in normal bone growth • This gene is found on chromosome #4

19. Achondroplasia • Because dwarfism was widely recorded in Egyptian art, it is considered the oldest recorded birth defect • 1/25,000 births result in achondroplasia • Over 80% of these births are to parents of normal height; they are the result of a spontaneous mutation

20. Huntington’s Disease • Genetically programmed degeneration of brain cells causing uncontrolled movements, loss of mental faculties, and emotional disturbance • Caused by an abnormal gene for the protein huntingtin. Huntingtin is believed to function in normal brain activity. • The gene is located on chromosome #4.

21. Huntington’s Disease • In the normal gene for huntingtin, there is a section of DNA with up to 28 CAG codons repeated. (This codes for glutamine.) • In the abnormal gene, there is 40 or more repeats of the CAG codon and subsequently, a longer chain of glutamine in the protein. • Chains of glutamine are known for causing other neurological disorders.

22. Huntington’s Disease • Symptoms usually do not appear until a person is in their 40’s • There are currently 1,500 people in the US with Huntington’s Disease • It affects males and females and all races at the same rate

23. Marfan Syndrome • Characterized by problems with the skeleton, eyes, heart, and blood vessels. • Caused by a mutation in the gene for the protein fibrillin. This protein is essential for the formation of elastic fibers in the connective tissue. • This gene is located on chromosome #15.

24. Marfan Syndrome • People with Marfan characteristically are tall with very long limbs and fingers • It is believed that Abraham Lincoln had Marfan Syndrome • Many times people do not know they have the disease and yet are susceptible to aortic rupture • 1/5,000 people in the US have Marfan Syndrome

26. Neurofibromatosis • Results in the growth of noncancerous tumors along nerves • Caused by a mutation in the gene for neurofibronin which is believed to act in tumor suppression. Therefore, if it is mutated, tumors are the result. • This gene is located on chromosome #17.

27. Neurofibromatosis • People afflicted have tumors that grow on their skin and can have bone deformity • 1/4,000 babies in the US are born with neurofibromatosis • 30 – 50% of the cases arise spontaneously • People usually lead a normal life

28. Osteogenesis Imperfecta • Characterized by bones that break frequently, often from no apparent cause • Results from abnormal production of collagen, the protein that is the primary constituent of the connective tissue (BOND IS A CONNECTIVE TISSUE!) • The gene for the alpha chain of collagen is located on chromosome #17, and the gene for the beta chain is on chromosome #7.

29. Osteogenesis Imperfecta • It is estimated there are 20,000 – 50,000 people in the US with OI • Many cases are the result of spontaneous mutations • The symptoms vary widely but with proper care, good diet, exercise, etc. people with OI can lead normal lives

30. X-Linked Recessive Females have to inherit two copies of the gene Males have to inherit one copy on the X from their mother

31. Duchenne Muscular Dystrophy • Characterized by progressive muscle weakness and wasting beginning early in life • Caused by a mutation in the gene for dystrophin • Dystrophin is the structural protein that provides support for muscle cells • No dystrophin—muscles do not work

32. Duchenne Muscular Dystrophy • 1/3,500 boys worldwide have DMD • Most are wheelchair bound by 10 and die by age 20 • Eventually cardiac and respiratory muscles waste away

33. Fragile X Syndrome • Most common cause of genetic mental impairment • Mutation in the Fragile X Mental retardation protein believed to help brain cells develop & function normally

34. Fragile X Syndrome • In the promoter region for the FMR1 gene, there are CGG repeats • In the normal gene there are 6 – 40 repeats • In the abnormal gene there may be hundreds of repeats • The more CGG is repeated the more severe the disease • Heterozygous females make enough FMR to have normal intelligence • 1/2000 males have Fragile X; 1/4,000 females

35. Fragile X

36. Hemophilia • Disorder resulting in improper blood clotting from cuts or from internal injuries • It is a result of a mutation in the gene for Blood Clotting Factor VIII • This protein is involved in stopping the flow of blood out of vessels when they are ruptured

37. ROYAL Hemophilia

38. Hemophilia • About 18,000 people (almost all male) in the US have hemophilia • 400 babies in the US each year are born with hemophilia • In the 1980’s approximately 10,000 children were infected with HIV because of transfusions for hemophilia • With proper treatment, hemophiliacs can live a normal life

39. Nondisjunction Disorders Caused by an abnormal number of a particular chromosome

40. Down Syndrome • Trisomy 21 • Low muscle tone, flat face, slanted eyes, abnormal shape and small size ears • Most have congenital heart defects • Suffer from mild to moderate mental retardation • With good care, most live to around age 55 • 1/800 to 1/1,000 live births result in Down Syndrome

41. Down Syndrome

42. Edward’s Syndrome • Trisomy 18 • Results in small jaw, low-set ears, malformation of the head, hands, feet; kidney and heart defects • 30% of babies die in first month • Less than 10% survive first year • Occurs in 1/6,000 live births • Twice as many females are born with Edward’s as are males

43. Edward’s Syndrome

44. Klinefelter’s Syndrome • XXY • Men affected have enlarged breasts, small testes, sparse facial and body hair, and inability to produce sperm • Some have lower IQ, many are very tall with long arms & legs • These men live as long as healthy individuals • 1/500 – 1/1,000 males in US have XXY • 3,000 males are born yearly with XXY

45. Klinefelter’s Syndrome

46. Patau Syndrome • Trisomy 13 • Results in cleft palate, polydactyly, severe mental deficiency, heart defects, and other abnormalities • Average lifespan is 3 days • Only 1 in 20 children survive longer than 6 months • Least common of all survivable trisomies • Occurs in 1/8,000 – 1/12,000 births • Birth rate favors females

47. Patau Syndrome

48. Turner Syndrome • Monosomy X • Inhibits sexual development and causes infertility • Females are usually short with webbed necks, drooping eyelids, bone development problems, and retarded secondary sex characteristics • IQ is usually normal • Occurs in 1/3,000 live births

49. Turner Syndrome