2. AP Biology 2008-2009 Human Genetic Diseases 12 3456

3. AP Biology Mutations Gene mutations are changes in the DNA code (one or more bases) Chromosome mutations are changes in the number or structure of chromosomes

4. AP Biology Causes of Gene mutations Mutagens are the original cause of mutations. If mutations affect the gametes they can be inherited. Somatic mutations only affect body cells and are not inherited. Ex.Thalidomide babies Examples of mutagens include: 1. Radiation (X-rays, ultraviolet rays) 2.Chemicals (Agent Orange, chemotherapy drugs)

5. AP Biology Pedigree analysis Pedigree analysis reveals Mendelian patterns in human inheritance  data mapped on a family tree = male= female= male w/ trait = female w/ trait

6. AP Biology Genetic counseling Pedigrees can help us understand the past & predict the future Thousands of genetic disorders are inherited as simple recessive traits  from benign conditions to deadly diseases albinism cystic fibrosis Tay sachs sickle cell anemia PKU

7. AP Biology Genetic testing sequencing individual genes Test parents Test baby- aminocentesis

8. AP Biology Recessive diseases-most common The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all  Heterozygotes (Aa) have a normal phenotype because one “normal” allele produces enough of the required protein We all have 7-8 unknown bad mutations

9. AP Biology Genetics & culture Why do all cultures have a taboo against incest?  laws or cultural taboos forbidding marriages between close relatives are fairly universal Fairly unlikely that 2 unrelated carriers of the same rare harmful recessive allele will meet & mate  but matings between close relatives increase risk “consanguineous” (same blood) matings  individuals who share a recent common ancestor are more likely to carry same recessive alleles Think of pure-bred dog They usually have inbred problems

10. AP Biology A hidden disease reveals itself AA x Aa AA male / sperm A a female / eggs Aa AA Aa AA Aa x aa Aa male / sperm A a female / eggs increase carriers in population hidden disease is revealed

11. AP Biology Cystic Fibrosis Primarily whites of European descent  strikes 1 in 2500 births 1 in 25 whites is a carrier (Aa)  normal allele codes for a membrane protein that transports Cl - across cell membrane defective or absent channels limit transport of Cl - & H 2 O across cell membrane thicker & stickier mucus coats around cells mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections  without treatment children die before 5; with treatment can live past their late 20s normal lung tissue

12. AP Biology Effect on Lungs Chloride channel transports salt through protein channel out of cell Osmosis: H 2 O follows Cl – airway Cl – H2OH2O H2OH2O mucus secreting glands bacteria & mucus build up thickened mucus hard to secrete normal lungs cystic fibrosis cells lining lungs Cl – channel

13. AP Biology loss of one amino acid

14. AP Biology enzyme Skin color: Albinism Johnny & Edgar Winter albino Africans albinism can be inherited as a single gene trait  aa = albino  Lack of enzyme involved in making melanin melanin = universal brown color tyrosine melanin albinism

15. AP Biology OCA1 albinoBianca Knowlton

16. AP Biology Albinism in animals

17. AP Biology Tay Saks Disease Primarily Jews of eastern European (Ashkenazi) descent & Cajuns  strikes 1 in 3600 births 100 times greater than incidence among non-Jews  non-functional enzyme fails to breakdown lipids in brain cells fats collect in cells destroying their function symptoms begin few months after birth seizures, blindness & degeneration of muscle & mental performance child usually dies before 5years

18. AP Biology Red spot in eye

19. AP Biology

20. PKU - Phenylketonurea Lack of an enzyme that is needed to metabolize phenylalanine – an amino acid found in many proteins If caught at birth, a very strict diet can prevent retardation that occurs when phenyalanine by-products build up in the brain.

21. AP Biology

22. PKU

23. AP Biology Sickle Cell Anemia Primarily Africans  strikes 1 out of 400 African Americans high frequency  caused by substitution of a single amino acid in hemoglobin  when oxygen levels are low, sickle-cell hemoglobin crystallizes into long rods deforms red blood cells into sickle shape sickling creates pleiotropic effects = cascade of other symptoms

24. AP Biology Sickle cell anemia Substitution of one amino acid in polypeptide chain hydrophilic amino acid hydrophobic amino acid

25. AP Biology

26. Sickle cell phenotype 2 alleles are codominant  both normal & mutant hemoglobins are synthesized in heterozygote (Ss)  50% cells sickle; 50% cells normal  carriers usually healthy  sickle-cell disease triggered under blood oxygen stress exercise

27. AP Biology Heterozygote advantage Malaria  single-celled eukaryote parasite spends part of its life cycle in red blood cells In tropical Africa, where malaria is common: High frequency of sickle cell allele in African Americans is vestige of African roots

28. AP Biology Prevalence of Malaria Prevalence of Sickle Cell Anemia

29. AP Biology Dominant Mutations Huntington’s Disease  repeated mutation on end of chromosome 4 mutation = CAG repeats glutamine amino acid repeats in protein one of 1 st genes to be identified  build up of “huntingtin” protein in brain causing cell death memory loss muscle tremors, jerky movements  “chorea” starts at age 30-50 early death  10-20 years after start 1872 Testing… Would you want to know?

30. AP Biology Polydactly-6 fingers

31. AP Biology Polydactyl

32. AP Biology Ptosis – also dominant

33. AP Biology Sex Linked Diseases Hemophilia SCIDS Color blindness

34. AP Biology

35. Chromosome defects Caused during meiosis-failure of chromosomes to attach to spindle or to separate at anaphase Ex. 1. Polyploidy – zygote is 3n, 4n, 5n, Only survives in plants Polyploid strawberries

36. AP Biology Non-disjunction Failure of one pair of chromosomes to separate in meiosis I or II Results in gametes which are n+1 or n-1 and zygotes which are 2n+1 or 2n-1 In humans gametes have 22 or 24 chromosomes Zygote results in 47 or 45 chromosomes in each cell

37. AP Biology http://www.youtube.com/watch? v=EA0qxhR2oOk http://glencoe.mcgraw- hill.com/olcweb/cgi/pluginpop.cg i?it=swf::550::400::/sites/dl/free/ 0078695104/383925/Chapter11 _NGS_VisualizingNondisjunctio n_10_10_06.swf::Visualizing%2 0Nondisjunction https://www.youtube.com/watch ?v=wFsxVkuChdU&nohtml5=Fa lse

38. AP Biology Nondisjunction

39. AP Biology Nondisjunction of Chromosome 21 Trisomy 21 – Down Syndrome Have 3 genes for traits with genes on 21 st chromosome

40. AP Biology Down Syndrome Karyotype

41. AP Biology Maternal age and Down Syndrome

42. AP Biology Nondisjunction can happen to any chromosome, but the effects usually cause death of the early embryo. Trisomy 18 sometimes survives but with many problems

43. AP Biology Nondisjunction of sex chromosomes Results in gametes that have extra or missing X or Y chromosomes. Zygote may be 47, XXX (Trisomy X) 47, XXY – Kleinfelter’s Syndrome 47, XYY – so called “criminal behavior” this was disproven 45, X Turner’s Syndrome 45, Y does not survive

44. AP Biology Barr Body Diagnosis A female with 2 is 47,XXX A Female with none is 45, X A Male with one is XXY

45. AP Biology Structural mutations Deletions, inversions, translocations and duplications