Genes, Chromosomes, and Human Genetics

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. 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

10. 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

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

12. 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

13. 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

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

15. 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

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

17. 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

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

19. 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

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

21. 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

22. 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

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

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

25. 13.3 Chromosomal Alterations That Affect Inheritance • Most common chromosomal alterations: deletions, duplications, translocations, and inversions • Number of entire chromosomes may also change

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

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

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

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

30. 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

31. 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

32. 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

33. 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

34. 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

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

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

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

38. X-Linked Recessive Inheritance • Recessive allele carried on X chromosome • Males • Recessive allele on X chromosome • Show symptoms • Females • Heterozygous carriers, no symptoms • Homozygous, show symptoms

39. Genetic Counseling • Identification of parental genotypes • Construction of family pedigrees • Prenatal diagnosis • Allows prospective parents to reach an informed decision about having a child or continuing a pregnancy

40. Genetic Counseling Techniques • Prenatal diagnosis tests cells for mutant alleles or chromosomal alterations • Cells obtained from: • Embryo • Amniotic fluid around embryo (amniocentesis) • Placenta (chorionic villus sampling) • Postnatal genetic screening • Biochemical and molecular tests

41. 13.5 Nontraditional Patterns of Inheritance • Cytoplasmic inheritance follows the pattern of inheritance of mitochondria or chloroplasts • In genomic imprinting, the allele inherited from one of the parents is expressed while the other allele is silent

42. Cytoplasmic Inheritance • Genes carried on DNA in mitochondria or chloroplasts • Cytoplasmic inheritance follows the maternal line • Zygote’s cytoplasm originates from egg cell

43. Cytoplasmic Inheritance • Mutant alleles in organelle DNA • Mendelian inheritance not followed (no segregation by meiosis) • Uniparental inheritance from female

44. Cytoplasmic Inheritance • Inheritance of variegation in Mirabalis

45. Genomic Imprinting • Expression of an allele is determined by the parent that contributed it • Only one allele (from either father or mother) is expressed • Other allele is turned off (silenced) • Often, result of methylation of region adjacent to gene responsible for trait