2. AP Biology 2006-2007 Beyond Mendel’s Laws of Inheritance Chapter 11

3. AP Biology Mendel’s Basic Pattern hold true for some diseases/disorders like:  Albinism  Cystic Fibrosis  Tay-Sachs Disease  Huntington’s Disease  Polydactyly

4. AP Biology enzyme Skin color: Albinism albino Africans inherited as a single gene trait Recessive = aa melanin = universal brown color tyrosine melanin albinism

5. AP Biology OCA1 albinoBianca Knowlton

6. 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

7. AP Biology Normal Lungs Chloride channel Transports chloride through protein channel out of cell Osmotic effects: H 2 O follows Cl - airway cells lining lungs Cl - Na + mucus secreting glands

8. AP Biology Cystic fibrosis airway cells lining lungs Cl - Na + bacteria & mucus build up thickened mucus hard to secrete damaged lung tissue

9. AP Biology

10. Tay-Sachs  Primarily Jews of eastern European (Ashkenazi) descent & Cajuns  strikes 1 in 3600 births  100 times greater than incidence among non-Jews or Mediterranean (Sephardic) Jews  non-functional enzyme fails to breakdown lipids in brain cells  symptoms begin few months after birth  seizures, blindness & degeneration of motor & mental performance  child usually dies before 5yo

11. AP Biology Recessive diseases  The diseases are recessive because the allele codes for either a malfunctioning protein or no protein at all  Heterozygotes (Aa)  carriers  have a normal phenotype because one “normal” allele produces enough of the required protein

12. AP Biology Heterozygote crosses Aa x Aa Aa male / sperm A a female / eggs AA Aaaa Aa A a A a AAAaaaAa  Heterozygotes as carriers of recessive alleles

13. AP Biology Some Diseases ARE DOMINANT  Huntington’s Chorea  Polydactyly

14. AP Biology Huntington’s chorea  Dominant inheritance  on end of chromosome 4  one of 1 st genes to be identified  mutation = CAG repeats = glutamine amino acid  build up of protein “huntington” in neurons (brain) causing cell death  memory loss  muscle tremors, jerky movements = “chorea”  early death (10-20 years after onset)  onset age 30-50 1872

15. AP Biology Woody Guthrie & Arlo Guthrie

16. AP Biology Polydactyly recessive allele far more common than dominant  only 1 individual out of 500 has more than 5 fingers/toes  so 499 out of 500 people are homozygous recessive (aa) the allele for >5 fingers/toes is DOMINANT & the allele for 5 digits is recessive individuals are born with extra fingers or toes

17. AP Biology Hound Dog Taylor

18. 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

19. AP Biology Extending Mendelian genetics  Mendel worked with a simple system  peas are genetically simple  most traits are controlled by a single gene  each gene has only 2 alleles, 1 of which is completely dominant to the other  The relationship between genotype & phenotype is rarely that simple

20. AP Biology Complex Patterns of Inheritance  MOST Inheritance is NOT simple Other Patterns of Inheritance are quite common  Incomplete and Codominance  Multiple Alleles  Pleiotrophy  Epistasis  Polygenic Traits  Sex-linked traits

21. AP Biology Incomplete dominance  Heterozygote shows an intermediate, blended phenotype  example:  RR = red flowers  rr = white flowers  Rr = pink flowers  make 50% less color RRRrrr

22. AP Biology Co-dominance true-breeding red flowers true-breeding white flowers X P 100% 100% pink flowers F 1 generation (hybrids) self-pollinate 25% white F 2 generation 25% red 1:2:1 50% pink It’s like flipping 2 pennies!

23. AP Biology Co dominance CRCR CWCW male / sperm CRCR CWCW female / eggs CRCRCRCR CRCWCRCW CWCWCWCW CRCWCRCW 25% 1:2:1 25% 50% 25% 1:2:1 % genotype % phenotype CRCRCRCR CRCWCRCW CRCWCRCW CWCWCWCW 25% 50% C R C W x C R C W

24. AP Biology Co-dominance AND Multiple Alleles  2 alleles affect the phenotype equally & separately not blended phenotype  example: ABO blood groups A and B are both dominant O is recessive 3 alleles so multiple alleles  I A, I B, i  I A & I B alleles are co-dominant to each other  both antigens are produced  both I A & I B are dominant to i allele

25. AP Biology Genetics of Blood type pheno- type genotype antigen on RBC antibodies in blood donation status AI A I A or I A i type A antigens on surface of RBC anti-B antibodies __ BI B I B or I B i type B antigens on surface of RBC anti-A antibodies __ ABI A I B both type A & type B antigens on surface of RBC no antibodies universal recipient Oi ii i no antigens on surface of RBC anti-A & anti-B antibodies universal donor

26. AP Biology Blood compatibility  Matching compatible blood groups  critical for blood transfusions  A person produces antibodies against antigens in foreign blood  wrong blood type  donor’s blood has A or B antigen that is foreign to recipient  antibodies in recipient’s blood bind to foreign molecules  cause donated blood cells to clump together  can kill the recipient Karl Landsteiner (1868-1943) 1901 | 1930

27. AP Biology Blood donation clotting

28. AP Biology Pleiotropy  Most genes are pleiotropic  one gene affects more than one phenotypic character  wide-ranging effects due to a single gene  dwarfism (achondroplasia)  gigantism (acromegaly)

29. AP Biology Acromegaly: André the Giant

30. AP Biology Aa x aa Inheritance pattern of Achondroplasia aa A a Aa A a Aa x Aa Aa aa Aa 50% dwarf:50% normal or 1:1 AA aa Aa 67% dwarf:33% normal or 2:1 Aa 

31. AP Biology Sickle cell anemia  Primarily Africans  strikes 1 out of 400 African Americans  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

32. AP Biology Sickle cell anemia  Substitution of one amino acid in polypeptide chain

33. AP Biology

34. Sickle cell phenotype(Sickle cell trait)  2 alleles are codominant  both normal & mutant hemoglobins are synthesized in heterozygote (Aa)  carriers usually healthy, although some suffer some symptoms of sickle-cell disease under blood oxygen stress  exercise

35. AP Biology Heterozygote advantage  Sickle cell frequency  high frequency of heterozygotes is unusual for allele with severe detrimental effects in homozygotes  1 out of 400 African Americans  Suggests some selective advantage of being heterozygous  sickle cell: resistance to malaria?  cystic fibrosis: resistance to cholera?

36. 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:  homozygous dominant individuals die of malaria  homozygous recessive individuals die of sickle cell anemia  heterozygote carriers are relatively free of both  High frequency of sickle cell allele in African Americans is vestige of African roots

37. AP Biology Malaria

38. AP Biology Epistasis B_C_ bbC_ _ _cc  One gene completely masks another gene  coat color in mice = 2 separate genes  C,c: pigment (C) or no pigment (c)  B,b: more pigment (black=B) or less (brown=b)  cc = albino, no matter B allele  9:3:3:1 becomes 9:3:4

39. AP Biology Epistasis in Labrador retrievers  2 genes: (E,e) & (B,b)  pigment (E) or no pigment (e)  pigment concentration: black (B) to brown (b) E–B–E–bbeeB–eebb

40. AP Biology Polygenic inheritance  Some phenotypes determined by additive effects of 2 or more genes on a single character  phenotypes on a continuum  human traits  skin color  height  weight  eye color  intelligence  behaviors

41. AP Biology Sex linked traits  Genes are on sex chromosomes  as opposed to autosomal chromosomes  first discovered by T.H. Morgan at Columbia U.  Drosophila breeding  good genetic subject  prolific  2 week generations  4 pairs of chromosomes  XX=female, XY=male 1910 | 1933 Thomas Hunt Morgan

42. AP Biology autosomal chromosomes sex chromosomes KARYOTYPE (Picture)of chromosomes made from pictures taken at metaphase

43. AP Biology RRrr What’s up with Morgan’s flies? x rr R R Rr 100% red eyes Rr x Rr R r RR Rrrr Rr 3 red : 1 white  Doesn’t work that way!

44. AP Biology F 2 generation 100% red-eye female 50% red-eye male 50% white eye male Discovery of sex linkage P X F 1 generation (hybrids) 100% red eye offspring true-breeding white-eye male true-breeding red-eye female

45. AP Biology  In humans & other mammals, there are 2 sex chromosomes: X & Y  2 X chromosomes  develop as a female: XX  an X & Y chromosome  develop as a male: XY Genetics of Sex XY X X XX XY 50% female : 50% male XX

46. AP Biology XRXRXRXR XrYXrY What’s up with Morgan’s flies? x XrXr Y XRXR 100% red eyes XRXR XRXrXRXr XRYXRY XRYXRYXRXrXRXr x  XRXrXRXr XRYXRY XRXR Y XRXR XrXr XRXrXRXr XRYXRYXRXRXRXR XrYXrY 100% red females 50% red males; 50% white males BINGO!

47. AP Biology Genes on sex chromosomes  Y chromosome  few genes other than turns on genes for production of male hormones  many effects = pleiotropy!  X chromosome  other genes/traits beyond sex determination  mutations:  hemophilia  Duchenne muscular dystrophy  color-blindness

48. AP Biology  Sex-linked  usually means “X-linked”  more than 60 diseases traced to genes on X chromosome Human X chromosome

49. AP Biology Sex-linked traits summary  X-linked  follow the X chromosomes  males get their X from their mother  trait is never passed from father to son  Y-linked  very few genes / traits  trait is only passed from father to son  females cannot inherit trait

50. AP Biology

52. Hemophilia Hh x HH XHYXHY XHXhXHXh XHXhXHXh XHXH XhXh XHYXHY Y XHXH sex-linked recessive XHXH Y male / sperm XHXH XhXh female / eggs XHXHXHXH XHXhXHXh XHYXHYXhYXhY XHXHXHXH XHYXHY XHXhXHXh XhYXhY carrierdisease

53. AP Biology X-inactivation  Female mammals inherit 2 X chromosomes  one X becomes inactivated during embryonic development  condenses into compact object = Barr body  which X becomes Barr body is random  patchwork trait = “mosaic” XHXhXHXh XHXHXhXh

54. AP Biology X-inactivation & tortoise shell cat  2 different cell lines in cat

55. AP Biology Nature vs. nurture  Phenotype is controlled by bothenvironment & genes Color of Hydrangea flowers is influenced by soil pH Human skin color is influenced by both genetics & environmental conditions Coat color in arctic fox influenced by heat sensitive alleles

56. AP Biology Genetic counseling  Pedigree 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

57. AP Biology Genetic testing