1. Chromosomes and Human Genetics Chapter 11

2. Genes Units of information about heritable traits In eukaryotes, distributed among chromosomes Each has a particular locus –Location on a chromosome

3. Homologous Chromosomes Homologous autosomes are identical in length, size, shape, and gene sequence Sex chromosomes are nonidentical but still homologous Homologous chromosomes interact, then segregate from one another during meiosis

4. Homologous Chromosomes

5. Alleles Different molecular forms of a gene Arise through mutation Diploid cell has a pair of alleles at each locus Alleles on homologous chromosomes may be same or different

6. Sex Chromosomes Discovered in late 1800s Mammals, fruit flies –XX is female, XY is male In other groups XX is male, XY female Human X and Y chromosomes function as homologues during meiosis

7. Sex Determination XX XY XX XY X X Y X sex chromosome combinations possible in new individual Y X sperm X X eggs Female germ cellMale germ cell

8. The Y Chromosome Fewer than two dozen genes identified One is the master gene for male sex determination –SRY gene (sex-determining region of Y) SRY present, testes form SRY absent, ovaries form

9. Effect of Y Chromosome - anatomical development 10 weeks Y present Y absent 7 weeks birth approaching appearance of structures that will give rise to external genitalia appearance of “uncommitted” duct system of embryo at 7 weeks Y present Y absent testis ovary testesovaries

10. The X Chromosome Carries more than 2,000 genes Most genes deal with nonsexual traits Genes on X chromosome can be expressed in both males and females

11. Viewing chromosomes

12. Karyotype Preparation - Stopping the Cycle Cultured cells are arrested at metaphase by adding colchicine This is when cells are most condensed and easiest to identify

13. Karyotype Preparation Arrested cells are broken open Metaphase chromosomes are fixed and stained Chromosomes are photographed through microscope Photograph of chromosomes is cut up and arranged to form karyotype diagram

14. Human Karyotype

15. Linkage groups Demo Need 20 students

16. Linkage Groups Genes on one type of chromosome Fruit flies –4 homologous chromosomes –4 linkage groups Indian corn –10 homologous chromosomes –10 linkage groups

17. Full Linkage x ABab 50% AB 50% ab All AaBb meiosis, gamete formation Parents: F 1 offspring: With no crossovers, half of the gametes have one parental genotype and half have the other A B a b A B a b a b A B

18. Incomplete Linkage Parents: F 1 offspring Unequal ratios of four types of gametes: All AaCc x meiosis, gamete formation ACac A C A C A C a c a c A c a C a c Most gametes have parental genotypes A smaller number have recombinant genotypes

19. Crossover Frequency Proportional to the distance that separates genes Crossing over will disrupt linkage between A and B more often than C and D

20. Cannot perform experiments on humans So……..

21. Human Genetic Analysis Geneticists often gather information from several generations to increase the numbers for analysis If a trait follows a simple Mendelian inheritance pattern they can be confident about predicting the probability of its showing up again

22. Pedigree Dogs? Cats?

23. Pedigree Chart that shows genetic connections among individuals Standardized symbols Knowledge of probability and Mendelian patterns used to suggest basis of a trait Conclusions most accurate when drawn from large number of pedigrees

24. HELLO, HELLO, HELLO, HELLO, HELLO, HELLO

25. Pedigree for Polydactyly… next slide too 67 12 5,5 6,6 6,6 5,5 5,6 6,7 6,6 * Gene not expressed in this carrier. * I II III IV V 5,5 6,6

26. Genetic Disorder A rare, uncommon version of a trait Polydactyly –Unusual number of toes or fingers –Does not cause any health problems –View of trait as disfiguring is subjective

27. Genetic Disorder Inherited conditions that cause mild to severe medical problems Why don’t they disappear? –Mutation introduces new rare alleles –In heterozygotes, harmful allele is masked, so it can still be passed on to offspring

28. Auto Sex-linked Dominant Recessive

29. Autosomal Dominant Inheritance Trait typically appears in every generation

30. Achondroplasia Autosomal dominant allele In homozygous form usually leads to stillbirth Heterozygotes display a type of dwarfism Have short arms and legs relative to other body parts

31. Huntington Disorder Autosomal dominant allele Causes involuntary movements, nervous system deterioration, death Symptoms don’t usually show up until person is past age 30 People often pass allele on before they know they have it

32. Auto Recessive….

33. Autosomal Recessive Inheritance Patterns If parents are both heterozygous, child will have a 25% chance of being affected

34. Galactosemia Caused by autosomal recessive allele Gene specifies a mutant enzyme in the pathway that breaks down lactose LACTOSEGALACTOSE GALACTOSE-1- PHOSOPHATE GALACTOSE-1- PHOSOPHATE enzyme 1enzyme 2enzyme 3 + glucose intermediate in glycolysis

35. Sex-linked

36. X-Linked Recessive Inheritance Males show disorder more than females Son cannot inherit disorder from his father

37. Examples of X-Linked Traits Color blindness –Inability to distinguish among some of all colors Hemophilia –Blood-clotting disorder –1/7,000 males has allele for hemophilia A –Was common in European royal families

38. Hutchinson-Guilford Progeria Mutation causes accelerated aging No evidence of it running in families Appears to be dominant Seems to arise as spontaneous mutation Usually causes death in early teens

39. Duplication Gene sequence that is repeated several to hundreds of times Duplications occur in normal chromosomes May have adaptive advantage –Useful mutations may occur in copy

40. Duplication

41. Inversion A linear stretch of DNA is reversed within the chromosome segments G, H, I become inverted

42. Deletion Loss of some segment of a chromosome Most are lethal or cause serious disorder segment C deleted

43. Translocation A piece of one chromosome becomes attached to another nonhomologous chromosome Most are reciprocal Philadelphia chromosome arose from a reciprocal translocation between chromosomes 9 and 22

44. Translocation

45. Philadelphia Chromosome First abnormal chromosome to be associated with a cancer Associated with a chronic leukemia –Overproduction of white blood cells

46. A Reciprocal Translocation 12 6 1315 1920 Chromosome 9 and chromosome 22 exchanged pieces

47. An Altered Gene When the reciprocal translocation occurred, a gene at the end of chromosome 9 fused with a gene from chromosome 22 This hybrid gene encodes an abnormal protein that stimulates uncontrolled division of white blood cells

48. Does Chromosome Structure Evolve? Alterations in the structure of chromosomes generally are not good and tend to be selected against Over evolutionary time, however, many alterations with neutral effects became built into the DNA of all species

49. Aneuploidy Individuals have one extra or less chromosome (2n + 1 or 2n - 1) Major cause of human reproductive failure Most human miscarriages are aneuploids

50. Polyploidy Individuals have three or more of each type of chromosome (3n, 4n) Common in flowering plants Lethal for humans –99% die before birth –Newborns die soon after birth

51. Nondisjunction n + 1 n - 1 chromosome alignments at metaphase I nondisjunction at anaphase I alignments at metaphase II anaphase IIchromosome number in gametes

52. Down Syndrome Trisomy of chromosome 21 Mental impairment and a variety of additional defects Can be detected before birth Risk of Down syndrome increases dramatically in mothers over age 35

53. Turner Syndrome Inheritance of only one X (XO) 98% spontaneously aborted Survivors are short, infertile females –No functional ovaries –Secondary sexual traits reduced –May be treated with hormones, surgery

54. Klinefelter Syndrome XXY condition Results mainly from nondisjunction in mother (67%) Phenotype is tall males –Sterile or nearly so –Feminized traits (sparse facial hair, somewhat enlarged breasts) –Treated with testosterone injections

55. XYY Condition Taller than average males Most otherwise phenotypically normal Some mentally impaired Once thought to be predisposed to criminal behavior, but studies now discredit

56. Genetic Screening Large-scale screening programs detect affected persons Newborns in United States routinely tested for PKU –Early detection allows dietary intervention and prevents brain impairment

57. Phenotypic Treatments Symptoms of many genetic disorders can be minimized or suppressed by –Dietary controls –Adjustments to environmental conditions –Surgery or hormonal treatments

58. Prenatal Diagnosis Amniocentesis Chorionic villus sampling Fetoscopy All methods have some risks

59. Genetic Counseling Parents-to-be can seek genetic counseling to compare risks of diagnostic procedures against the risk that their child will be affected by a severe genetic disorder

60. Preimplantation Diagnosis Used with in-vitro fertilization Mitotic divisions produce ball of 8 cells All cells have same genes One of the cells is removed and its genes analyzed If cell has no defects, the embryo is implanted in uterus