Chromosomes and Human Genetics

1. Chromosomes andHuman Genetics Chapter 12

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. 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

5. Studying Human Genetics • Studying Human Genetics is much more complicated than using other model systems (e.g. Pea Plants) • Humans reproduce slowly, have few offspring, and it is unethical to breed humans for experiments • There are many techniques that are used to study human genetics indirectly • Karyotypes • Pedigree analysis • Linkage maps

6. Karyotype • Picture of an individual’s chromosomes • Making a Karyotype: • Metaphase chromosomes are fixed and stained • Chromosomes are photographed through microscope • Photograph of chromosomes is cut up and arranged to form karyotype diagram

7. Karyotype Autosomes Sex Chromosomes

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

9. X X x X Y x Y X X X XX XX XY XY Sex Determination female (XX) male (XY) eggs sperm Figure 12.5Page 198

10. 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

11. The X Chromosome • Carries more than 2,300 genes • Most genes deal with nonsexual traits • Genes on X chromosome can be expressed in both males and females

12. Pedigree • A chart showing the genetic connections between individuals • A genetic family tree • Often groups of people whose heritage is well documented or who are somewhat isolated from others are used to develop pedigrees. • E.g. Icelanders, Mormons, Ashkenazi Jews, Amish, Sardinians

13. Pedigree Symbols male female marriage/mating offspring in order of birth, from left to right Individual showing trait being studied sex not specified generation I, II, III, IV...

14. I II III IV V *Gene not expressed in this carrier. Example: Pedigree of Polydactyly female male 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 5,5 6,6 5,6 6,7 12 6,6 6,6

15. Polydactyly or Extra Digits

16. Linked Genes • Genes found on one type of chromosome • Linked genes can assort separately from on another only through crossing over • The closer to genes are to each other on a chromosome, the more tightly linked they are (i.e. the more likely they are to assort together during meiosis

17. A B C D a b c d A B C D a b c d A B c d a b C D Markers A & B are linked Markers A & C are not linked

18. A A a B B b A a B b a b Full Linkage x Parents: AB ab F1 offspring: All AaBb meiosis, gamete formation Equal ratios of two types of gametes: 50% AB 50% ab

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

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

21. Linkage mapping • Done by using known “landmarks” or markers on chromosomes • These markers are either genes or DNA fragments whose location has already been worked out • By watching how these markers are inherited by those with & without the disorder, geneticists can predict the location of the gene responsible for the disorder • If a gene and a marker are found together 100% of the time, they are completely linked • If a gene and a marker are found together 50% of the time they are completely unlinked

22. Human Genetic Conditions • A genetic abnormality is an uncommon or rare trait • E.g. Polydactyly • A genetic disorder is an inherited condition that may cause medical problems • E.g. Cystic Fibrosis • A syndrome is a set of symptoms that characterize a disorder • E.g. Down Syndome

23. Human Genetic Abnormalities/Disorders • Different patterns of inheritance are observed depending on the condition: • Autosomal Recessive Inheritance • Autosomal Dominant Inheritance • X-linked inheritance

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

25. Albinism

26. Autosomal Dominant Inheritance Trait typically appears in every generation

27. 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

28. 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

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

30. Color Blindness

31. Hemophilia

32. Chromosomal Mutations • Duplication • Deletion • Inversion • Translocation

33. 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

34. Duplication normal chromosome one segment repeated three repeats

35. Inversion A linear stretch of DNA is reversed within the chromosome segments G, H, I become inverted In-text figurePage 206

36. 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

37. Translocation one chromosome a nonhomologous chromosome nonreciprocal translocation In-text figurePage 206

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

39. 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

40. Polyploidy Individuals have three or more of each type of chromosome (3n, 4n) Common in flowering plants Found in some fish & amphibians Lethal for humans

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. Nondisjunction n + 1 n + 1 n - 1 chromosome alignments at metaphase I n - 1 nondisjunction at anaphase I alignments at metaphase II anaphase II Figure 12.17Page 208

43. 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

44. Aneuploidy Having one extra or one less chromosome Downs Syndrome trisomy 21 Turners Syndrome XO Klinefelters XXY Downs Syndrome

45. Trisomy and monosomy in sex chromosomes

46. 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

47. 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

48. Turners Syndrome Klinefelters Syndrome

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. 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