The Chromosomal Basis of Inheritance

1. The Chromosomal Basis ofInheritance Campbell & Reece Chapter 15

2. Chromosome Theory of Inheritance 1860: Mendel 1875: stages of mitosis 1890: stages of meiosis 1902: Walter Sutton & Theodor Boveri noted parallels between Mendel’s “factors” & what chromosomes do in mitosis & meiosis

3. Chromosome Theory of Inheritance Chromosomes & genes are present in pairs in diploid cells Homologous chromosomes separate during meiosis Fertilization restores chromosomes to 2n Chromosomes segregate & assorts independently

5. Morgan’s Experiment • provided 1st evidence that associated specific gene with specific chromosome • Drosophila melanogaster (fruit flies) • 100’s offspring from 1 mating • new generation q2 wks • 4 chromosomes (3 pair autosomes/1 pair sex chromosomes)

6. Morgan’s Experiment after months of mating & inspecting each fly Morgan finally got what he wanted: normally fruit flies have red eyes; now he had one with white eyes

7. Morgan’s Experiment • wild type: the phenotype for a character most commonly observed in natural populations • any alternative is mutant phenotype • symbols: • w+ wild type (“w” for white eyes)

8. Morgan’s Experiment mated white eyed male x w+ female

9. Morgan’s Experiment white-eyed trait showed up only in male offspring: 100% F2 females red eyes 50% F2 males white eyes/ 50% red eyes suggested that gene for eye color located on X chromosome

11. Sex-Linked Genes: Unique Patterns of Inheritance • in mammals: • ova: 1 X chromosome • sperm: 50% X chromosome/ 50% Y chromosome • short segments of X & Y are homologous & there is opportunity for crossing over in Prophase I

12. Other Chromosomal Systems of Sex Determination

13. Sex-Linked Gene • any gene located on either sex chromosome • very few genes on Y chromosome so very few Y-linked • most related to male-ness • rare example • produces abnl sperm

14. X-Linked Genes ~1,100 genes many unrelated to sex

15. X-Linked Recessive Traits • terms homozygous * heterozygous lack meaning when describing X-linked genes • males only have 1 copy • females will have 2 copies • rare, but not impossible for female to show recessive phenotype

16. X-Linked Recessive Disorders Color-blindness Duchenne Muscular Dystrophy Hemophilia

19. X Chromosome Inactivation in Female Mammals 1 of the 2 X’s in females becomes inactivated during embryonic development Barr body: inactive X condenses, found along inside edge of nuclear envelope selection of which X will inactivate occurs randomly & independently in each embryonic cell …. females are a mosaic of the 2 X chromosomes

20. Barr Bodies

21. Inactivating an X involves modification of DNA & the histone proteins bound to it (includes attachment of methyl groups, ---CH3) several genes on each X involved in inactivation process XIST gene (X-inactive specific transcript) becomes active only on the X that will become the Barr body

23. Gene Linkage Linked Genes: genes located near each other on same chromosome & tend to be inherited together in genetic crosses results of genetic crosses deviate from what is expected using the Law of Independent Assortment

25. How Linkage Affects Inheritance • Morgan’s Drosophila experiments: • Wild-type flies have gray bodies & normal-sized wings • thru breeding Morgan produced flies with black bodies & much smaller wings (vestigial wings) • both characters have genes not on the X chromosome & both are recessive to the wild type

28. Morgan’s Experiments with Linkage results had much higher proportion of the combinations of traits seen in P generation flies than would be expected if the 2 genes assorted independently Morgan concluded that body color & wing size are usually inherited together in parental combinations because the genes for these characters are near each other on the same chromosome

29. Genetic Recombination • production of offspring with combinations of traits that differ from those found in either parent • occurs with unlinked genes in simple dihybrid cross of parents heterozygous for the 2 characters • phenotypes that match those of the parents called: parental types • phenotypes that do not match those of parents called: recombinant types or recombinants • if 50% of offspring are recombinants: 50% frequency of recombination: will see 50% if the 2 genes in testcrtoss are on different chromosomes

30. Cross of hybrid parents

31. Recombination of Linked Genes • back to Morgan’s flies: saw >50% (most) offspring with parental types so conclude these genes are linked • What about the 17% that were recombinants? • Answer: Crossing Over (1st proposed by Morgan) • proteins in Prophase I orchestrate an exchange of corresponding segments of 1 maternal chromosome with its homolog

33. Recombinant Chromosomes add to Genetic Variation many new genetic variations possible thru crossing over random fertilization then increases even further the # of variant allele combinations that can be created

34. Mapping Distances between Genes • genetic map: an ordered list of the genetic loci along a particular chromosome • 1st done by Sturtevant (student of Morgan) • hypothesized the % of recombinant offspring (recombination frequency) depends on the distance between genes on a chromosome • assumed crossing over a random event, equally likely to occur anywhere along length of a chromosome

35. Linkage Map • Sturtevant predicted that the farther apart 2 genes are, the higher the probability that a crossover will occur between them & therefore the higher the recombination frequency. • Linkage Map: genetic map based on recombination frequencies • Map Unit: distances between genes with: • 1 map unit = 1% recombinant frequency

38. Genetic Disorders due to Chromosomal Abnl • large-scale chromosomal changes • many  abortion of fetus (spontaneous miscarriage) • Chromosomes can be damaged: • in meiosis • by chemical or physical means

39. Abnormal Chromosome # occasionally, meiotic spindle does not distribute chromosomes equally nondisjunction: an error in meiosis or mitosis in which members of a pair of homologous chromosomes or a pair of sister chromatids fail to separate properly from each other

40. Nondisjunction in Meiosis I

41. Nondisjunction when any of the gametes in last slide go thru fertilization  zygote with abnl # of a particular chromosome: condition called aneuploidy if 1 gamete has 0 copies of chromosome the aneuploid zygote is said to be monosomic for that chromosome if 1 gamete has 2 copies of chromosome the aneuploid zygote is said to be trisomic for that chromosome

42. Aneuploidy

43. Aneuploidy Mitosis will subsequently transmit the anomaly to all embryonic cells (most of these zygotes will end in spontaneous abortion) those that survive it has characteristic set of traits (syndrome) if nondisjunction takes place during mitosis in early embryonic development  passed to large # of cells & is likely to have substantial effect on organism

44. Polyploidy 2 or more complete sets of chromosomes in all somatic cells: 3n = triploidy 4n = tetraploidy individuals appear more normal than having 1 extra or 1 missing chromosome common in plant kingdom 3n: bananas 6n: wheat 8n: strawberries animal kingdom: few examples: fish & amphibians

46. Which is polyploid?

47. Alterations of Chromosome Structure breakage in chromosome can lead to 4 types of changes: deletion: chromosome fragment is lost duplication: “deleted” fragment attaches to some other chromosome inversion: fragment reattaches to original chromosome but is in reverse orientation translocation: fragment joins a nonhomologous chromosome

48. Alterations in Chromosome Structure • deletions & duplications likely to occur during meiosis • sometime crossing over exchange unequal fragments • If missing any # of essential genes condition is usually lethal • translocations & inversions can alter phenotype because a gene’s expression can be influences by its location among neighboring genes

49. Human Disorders due to Chromosomal Alterations Trisomy 21 (Down Syndrome) 1/700 children born in USA each have 47 chromosomes (extra 21st) characteristic facial features, short stature, treatable heart defects, developmental delays, increased risk of leukemia, Alzheimer’s disease, and a lower rate of hypertension, atherosclerosis, stroke, many types of solid tumors

50. Trisomy 21 Features