Chromosomes and Human Genetics

1. Chromosomes andHuman 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. X X X Y Y X X X XX XX XY XY Sex Determination eggs sperm Female germ cell Male germ cell sex chromosome combinations possible in new individual

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. appearance of structures that will give rise to external genitalia appearance of “uncommitted” duct system of embryo at 7 weeks Effect of YChromosome 7 weeks Y present Y absent Y present Y absent testes ovaries 10 weeks ovary testis birth approaching

10. The X Chromosome • Carries more than 2,062 genes • Most genes deal with nonsexual traits • Genes on X chromosome can be expressed in both males and females

11. 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

12. 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

13. Human Karyotype

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

15. A A a B B b A a B b a b Full Linkage AB ab Parents: x F1 offspring: All AaBb meiosis, gamete formation 50%AB 50%ab With no crossovers, half of the gametes have one parental genotype and half have the other

16. A a a c c C A C Incomplete Linkage AC ac x Parents: F1 offspring All AaCc meiosis, gamete formation Unequal ratios of four types of gametes: a a A A C c C c Most gametes have parental genotypes A smaller number have recombinant genotypes

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

18. 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

19. 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

20. I II III IV V *Gene not expressed in this carrier. Pedigree for Polydactyly 5,5 6,6 5,5 6,6 * 5,5 6,6 6,6 5,5 6,6 5,5 6 7 5,5 6,6 5,5 6,6 5,5 6,6 5,6 6,7 12 6,6 6,6

21. 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

22. 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

23. Autosomal Dominant Inheritance • Trait typically appears in every generation

24. 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

25. 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

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

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

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

29. 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

30. 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

31. 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

32. Duplication

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

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

35. 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

36. Translocation

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

38. A Reciprocal Translocation 1 2 Chromosome 9 and chromosome 22 exchanged pieces 6 13 15 19 20

39. 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

40. 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

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

42. 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

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

44. 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

45. 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

46. 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

47. 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

48. 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

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

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