1. Genes, Chromosomes, and Human Genetics Chapter 13

2. Why It Matters • Progeria

3. 13.1 Genetic Linkage and Recombination • The principles of linkage and recombination were determined with Drosophila • Recombination frequency can be used to map chromosomes • Widely separated linked genes assort independently

4. Chromosomes • Genes • Sequences of nucleotides in DNA • Arranged linearly in chromosomes

5. Linked Genes • Genes carried on the same chromosome • Linked during transmission from parent to offspring • Inherited like single genes • Recombination can break linkage

6. Drosophila melanogaster • Fruit fly • Model organism for animal genetics • Compared to Mendel’s peas • Used to test linkage and recombination

7. Gene Symbolism • Normal alleles (wild-type) • Usually most common allele • Designated by “+” symbol • Usually dominant Wild-typeMutant + = red eyes pr = purple + = normal wings vg = vestigial wings

8. Genetic Recombination • Alleles linked on same chromosome exchange segments between homologous chromosomes • Exchanges occur while homologous chromosomes pair during prophase I of meiosis

9. Evidence for Gene Linkage

10. Recombination Frequency • Amount of recombination between two genes reflects the distance between them • The greater the distance, the greater the recombination frequency • Greater chance of crossover between genes

11. Recombination Frequency

12. Chromosome Maps • Recombination frequencies used to determine relative locations on a chromosome • Linkage map for genes a, b, and c: • 1 map unit = 1% recombination = 1 centimorgan

13. Map: Drosophila Chromosome 2

14. Recombination Occurs Often • Widely separated linked genes often recombine • Seem to assort independently • Detected by testing linkage to genes between them

15. 13.2 Sex-Linked Genes • In both humans and fruit flies, females are XX, males are XY • Human sex determination depends on the Y chromosome

16. 13.2 (cont.) • Sex-linked genes were first discovered in Drosophila • Sex-linked genes in humans are inherited as they are in Drosophila • Inactivation of one X chromosome evens out gene effects in mammalian females

17. Sex Chromosomes • Sex chromosomes determine gender • X and Y chromosomes in many species • XX: female • XY: male • Other chromosomes are called autosomes

18. Sex Determination in Humans

19. Human Sex Chromosomes • Human X chromosome • Large (2,350 genes) • Many X-linked genes are nonsexual traits • Human Y chromosome • Small (few genes) • Very few match genes on X chromosome • Contains SRY gene • Regulates expression of genes that trigger male development

20. Sex Linkage • Female (XX): 2 copies of X-linked alleles • Male (XY): 1 copy of X-linked alleles • Only males have Y-linked alleles

21. Sex Linkage • Males have only one X chromosome • One copy of a recessive allele results in expression of the trait • Females have two X chromosomes • Heterozygote: recessive allele hidden (carrier) • Homozygote recessive: trait expressed

22. Eye Color Phenotypes in Drosophila • Normal wild-type: red eye color • Mutant: white eye color

23. Evidence for Sex-Linked Genes

24. Animation: Morgan’s reciprocal crosses

25. Human Sex-Linked Genes • Pedigree chart show genotypes and phenotypes in a family’s past generations • X-linked recessive traits more common in males • Red-green color blindness • Hemophilia: defective blood clotting protein

26. Inheritance of Hemophilia • In descendents of Queen Victoria of England

27. X Inactivation (1) • Dosage compensation • In female mammals, inactivation of one X chromosome makes the dosage of X-linked genes the same as males • Occurs during embryonic development

28. X Inactivation (2) • Random inactivation of either X chromosome • Same X chromosome inactivated in all descendents of a cell • Results in patches of cells with different active X chromosomes

29. Calico Cats • Heterozygote female (no male calico cats)

30. Barr Body • Tightly coiled condensed X chromosome • Attached to side of nucleus • Copied during mitosis but always remains inactive

31. 13.3 Chromosomal Alterations That Affect Inheritance • Most common chromosomal alterations: deletions, duplications, translocations, and inversions • Number of entire chromosomes may also change

32. Chromosomal Alterations (1) • Deletion: broken segment lost from chromosome • Duplication: broken segment inserted into homologous chromosome

33. Chromosomal Alterations (2) • Translocation: broken segment attached to nonhomologous chromosome • Inversion: broken segment reattached in reversed orientation

34. Nondisjunction (1) • Failure of homologous pair separation during Meiosis I

35. Nondisjunction (2) • Failure of chromatid separation during Meiosis II

36. Changes in Chromosome Number • Euploids • Normal number of chromosomes • Aneuploids • Extra or missing chromosomes • Polyploids • Extra sets of chromosomes (triploids, tetraploids) • Spindle fails during mitosis

37. Aneuploids • Abnormalities usually prevent embryo development • Exception in humans is Down syndrome • Three copies of chromosome 21 (trisomy 21) • Physical and learning difficulties • Frequency of nondisjunction increases as women age

38. Down Syndrome

39. Aneuploidy of Sex Chromosomes

40. Aneuploidy of Sex Chromosomes

41. Animation: Karyotype preparation

42. Polyploids • Common in plants • Polyploids often hardier and more successful • Source of variability in plant evolution • Uncommon in animals • Usually has lethal effects during embryonic development

43. 13.4 Human Genetics and Genetic Counseling • In autosomal recessive inheritance, heterozygotes are carriers and homozygous recessives are affected by the trait • In autosomal dominant inheritance, only homozygous recessives are unaffected

44. 13.4 (cont.) • Males are more likely to be affected by X-linked recessive traits • Human genetic disorders can be predicted, and many can be treated

45. Modes of Inheritance • Autosomal recessive inheritance • Autosomal dominant inheritance • X-linked recessive inheritance

46. Autosomal Recessive Inheritance • Males or females carry a recessive allele on an autosome • Heterozygote • Carrier • No symptoms • Homozygote recessive • Shows symptoms of trait

47. Autosomal Recessive Inheritance

48. Cystic Fibrosis

49. Autosomal Dominant Inheritance • Dominant gene is carried on an autosome • Homozygote dominant or heterozygote • Show symptoms of the trait • Homozygote recessive • Normal

50. Autosomal Dominant Inheritance