BIOL 102 Chp 15 PowerPoint


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BIOL 102 Chp 15 PowerPoint

  1. 1. Chapter 15 The Chromosomal Basis of Inheritance Rob Swatski Associate Professor of Biology HACC – York Campus1
  2. 2. Overview: Genes and Chromosomes We know Mendel’s “hereditary factors” are genes We know genes are located on chromosomes in specific regions (loci) - Fluorescent “tagging” 2
  3. 3. Mitosis & meiosis were first described in the late 1800’s The chromosome theory of inheritance: - Mendelian genes have specific loci on chromosomes - Chromosomes undergo segregation & independent assortment Chromosome behavior during meiosis accounts for Mendel’s laws 3
  4. 4. P Generation Gametes Meiosis Fertilization Yellow-round seeds (YYRR) Green-wrinkled seeds (yyrr) All F1 plants produce yellow-round seeds (YyRr) y y y r r r Y Y YR RR  4
  5. 5. 0.5 mm Meiosis Metaphase I Anaphase I Metaphase II Gametes LAW OF SEGREGATION The two alleles for each gene separate during gamete formation. LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation. 1 4 yr 1 4 Yr1 4 YR 3 3 F1 Generation 1 4 yR R R R R RR R R R R R R Y Y Y Y Y YY Y YY YY y r r rr r r rr r r r r y y y y y y y yyy y All F1 plants produce yellow-round seeds (YyRr) 1 2 2 1 5
  6. 6. F2 Generation 3Fertilization recombines the R and r alleles at random. Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation. An F1  F1 cross-fertilization 9 : 3 : 3 : 1 LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT 3 6
  7. 7. Morgan’s Experimental Evidence • The 1st solid evidence associating a specific gene with a specific chromosome came from the embryologist, Thomas Hunt Morgan • Morgan’s experiments with fruit flies provided convincing evidence that Mendel’s heritable factors are located on chromosomes 7
  8. 8. 8 The “Fly Room” @ Columbia University
  9. 9. 9
  10. 10. 10 Drosophila melanogaster
  11. 11. Why Fruit Flies? - Fast breeding rate & lots of offspring - New generation produced every 2 weeks - The have only 4 pairs of chromosomes 11
  12. 12. Wild type (normal) phenotypes were common in the fly populations Traits alternative to the wild type are called mutant phenotypes wild type mutant 12
  13. 13. Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair In one mating experiment, Morgan crossed: - male white eyes (mutant) with female red eyes (wild type) - The F1 generation all had red eyes - The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes - The white-eyed mutant allele must be on the X chromosome Morgan’s finding supported the chromosome theory of inheritance 13
  14. 14. All offspring had red eyes. P Generation F1 Generation F2 Generation RESULTS EXPERIMENT 14
  15. 15. F2 Generation P Generation Eggs Eggs Sperm Sperm X w CONCLUSION X X Y w w w w w w w w w w w w w w w w F1 Generation 15
  16. 16. The Chromosomal Basis of Sex In humans & other mammals, there are 2 varieties of sex chromosomes: - larger X chromosome - smaller Y chromosome Only the ends of Y chromosomes are homologous with corresponding regions of the X chromosomes The SRY gene on the Y chromosome codes for the development of testes X Y 16
  17. 17. (a) The X-Y system: females are XX and males are XY 44 + XY 44 + XX Parents 44 + XY 44 + XX 22 + X 22 + X 22 + Yor or Sperm Egg + Zygotes (offspring) 17
  18. 18. (b) The X-0 system (insects) 22 + XX 22 + X (c) The Z-W system (birds, fishes, insects) - Sex chromosomes are present in the egg (not sperm) 76 + ZW 76 + ZZ X0 18
  19. 19. (d) The haplo-diploid system (bees & ants) - No sex chromosomes 32 (Diploid) 16 (Haploid) 19
  20. 20. Inheritance of Sex-Linked Genes Sex-linked gene: a gene that is located on either sex chromosome - in humans, this usually refers to x-linked genes, which are genes located on the X chromosome (there are few Y-linked genes) - X chromosomes have genes for many characters, most unrelated to sex - contains 2000 genes 20
  21. 21. X-linked genes follow specific patterns of inheritance For a recessive sex-linked trait to be expressed: - A female needs 2 copies of the allele (XnXn) = homozygous - A male needs only 1 copy of the allele (XnY) = hemizygous Sex-linked recessive disorders are much more common in males than in females – why? 21
  22. 22. (a) (b) (c) XN XN Xn Y XN Xn   XN Y XN Xn  Xn Y YXn SpermYXN SpermYXn Sperm XN Xn Eggs XN XN XN Xn XN Y XN Y Eggs XN Xn XN XN Xn XN XN Y Xn Y Eggs XN Xn XN Xn Xn Xn XN Y Xn Y Transmission of Sex-Linked Recessive Traits 22
  23. 23. Sex-linked recessive disorders in humans include: - Color blindness - Duchenne muscular dystrophy - Hemophilia 23
  24. 24. X-inactivation in Female Mammals In female mammals, 1 of the two X chromosomes in each cell is randomly inactivated during embryonic development - the inactive X condenses into a Barr body If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character 24
  25. 25. X chromosomes Early embryo: Allele for orange fur Allele for black fur Cell division & X chromosome inactivation 2 cell populations in adult cat: Active X Active X Inactive X Black fur Orange fur 25 Tortoiseshell cat
  26. 26. Linked genes: located near each other on the same chromosome - Linked genes are usually inherited together 26
  27. 27. How Linkage Affects Inheritance Morgan experimented with fruit flies to see how linkage affects the inheritance of 2 characters He crossed flies that differed in: - body color & wing size 27
  28. 28. P Generation (homozygous) Wild type (gray body, normal wings) F1 dihybrid (wild type) Testcross offspring TESTCROSS b b vg vg b b vg vg b b vg vg b b vg vg Double mutant (black body, vestigial wings) Double mutant Eggs Sperm EXPERIMENT RESULTS PREDICTED RATIOS Wild type (gray-normal) Black- vestigial Gray- vestigial Black- normal b vg b vg b vg b vg b b vg vg b b vg vg b b vg vg b b vg vg 965 944 206 185 1 1 1 1 1 0 1 0 If genes are located on different chromosomes: If genes are located on the same chromosome and parental alleles are always inherited together: : : : : : : : : : b vg 28
  29. 29. Conclusion: body color & wing size are usually inherited together in specific combinations (parental phenotypes) These genes do not assort independently & Morgan reasoned that they were on the same chromosome 29
  30. 30. Most offspring (F2) F1 dihybrid female & homozygous recessive male in testcross or b+ vg+ b vg b+ vg+ b vg b vg b vg b vg b vg Results: a much higher % of parental phenotypes than would be expected by independent assortment 30
  31. 31. However, non-parental phenotypes were also produced Understanding this result involves exploring genetic recombination - the production of offspring with combinations of traits different from either parent Both findings of Mendel & Morgan relate to the chromosomal basis of recombination 31
  32. 32. Recombination of Unlinked Genes: Independent Assortment of Chromosomes Mendel observed that combinations of traits in some offspring differ from either parent - Parental types: offspring with a phenotype matching 1 of the parental phenotypes - Recombinant types (recombinants): offspring with non-parental phenotypes (new combinations of traits) A 50% frequency of recombination is observed for any 2 genes on different chromosomes 32
  33. 33. YyRr Gametes from green- wrinkled homozygous recessive parent (yyrr) Gametes from yellow-round heterozygous parent (YyRr) Parental- type offspring Recombinant Offspring (50%) yr yyrr Yyrr yyRr YR yr Yr yR 33
  34. 34. Recombination of Linked Genes: Crossing Over Morgan discovered that genes can be linked, but the linkage was incomplete (as shown by the appearance of recombinant phenotypes) Morgan proposed that some process must sometimes break the physical connection between genes on the same chromosome = the crossing over of homologous chromosomes during meiosis 34
  35. 35. Testcross parents Replication of chromo- somes Gray body, normal wings (F1 dihybrid) Black body, vestigial wings (double mutant) Replication of chromo- somes b+ vg+ b+ vg+ b+ vg+ b vg b vg b vg b vg b vg b vg b vg b vg b vg b+ vg+ b+ vg b vg+ b vg Recombinant chromosomes Meiosis I and II Meiosis I Meiosis II Eggs Sperm b+ vg+ b vg b+ vg b vgb vg+ Crossing- over 35
  36. 36. Testcross offspring 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal b+ vg+ b vg b vg b vg b+ vg b vg b vg b+ vg+ Spermb vg Parental-type offspring Recombinant offspring (206 + 185 = 391) b vg b+ vg b vg+ b vg+ Recombination frequency = 391 recombinants 2,300 total offspring  100 = 17% Eggs Recombinant chromosomes 36
  37. 37. Recombinant chromosomes bring alleles together in new combinations in gametes Random fertilization further increases the number of variant combinations that can be produced This abundance of genetic variation is the raw material upon which natural selection works New Combinations of Alleles: Variation for Normal Selection 37
  38. 38. Genetic Maps Alfred Sturtevant, one of Morgan’s students, constructed a genetic map: an ordered list of loci along a particular chromosome 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 38
  39. 39. Linkage Maps Genetic map of a chromosome based on recombination frequencies Distances between genes expressed as map units: 1 map unit (centimorgan) = 1% recombination frequency Map units indicate relative distance & order, not precise locations of genes 39
  40. 40. RESULTS Recombination frequencies Chromosome 9% 9.5% 17% b cn vg 40
  41. 41. Genes that are far apart on the same chromosome can have a recombination frequency near 50% Such genes are physically linked, but genetically unlinked, & behave as if found on different chromosomes 41
  42. 42. Sturtevant used recombination frequencies to make linkage maps of fruit fly genes Using methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomes - Indicate positions of genes with respect to chromosomal features 42
  43. 43. Mutant phenotypes Short aristae Black body Cinnabar eyes Vestigial wings Brown eyes Red eyes Normal wings Red eyes Gray body Long aristae (appendages on head) Wild-type phenotypes 0 48.5 57.5 67.0 104.5 A partial linkage map of a Drosophila chromosome 43
  44. 44. Large-scale chromosomal alterations often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders Plants tolerate such genetic changes better than animals do Alteration of Chromosome Number or Structure Cause Some Genetic Disorders 44
  45. 45. Abnormal Chromosome Number Nondisjunction: pairs of homologous chromosomes do not separate normally during meiosis - As a result, one gamete receives 2 of the same type of chromosome & another gamete receives no copy 45
  46. 46. Meiosis I Nondisjunction of homologous chromosomes (a) Nondisjunction of homologous chromosomes in meiosis I (b) Nondisjunction of sister chromatids in meiosis II Meiosis II Nondisjunction of sister chromatids Gametes Number of chromosomes n + 1 n + 1 n + 1n – 1 n – 1 n – 1 n n 46 Normal
  47. 47. Aneuploidy: results from the fertilization of gametes in which nondisjunction occurred - offspring have an abnormal number of a particular chromosome Monosomic zygote: has only 1 copy of a particular chromosome (ex: Turner Syndrome – females have 1 X chromosome); most others lethal Trisomic zygote: has 3 copies of a particular chromosome (ex: Trisomy 21 – Down Syndrome) 47
  48. 48. Polyploidy: organism has more than 2 complete sets of chromosomes - Common in plants, but not animals (in some flatworms & leeches) - Polyploids are more normal in appearance than aneuploids - Triploidy (3n): 3 sets of chromosomes (Ex: seedless watermelons) - Tetraploidy (4n): 4 sets of chromosomes (Ex: cotton, salmon) 48
  49. 49. Alterations of Chromosome Structure Breakage of a chromosome can lead to 4 types of changes in structure: - Deletion: removes a chromosomal segment - Duplication: repeats a segment - Inversion: reverses the orientation of a segment within a chromosome - Translocation: moves a segment from 1 chromosome to another non-homologous chromosome 49
  50. 50. (a) Deletion (b) Duplication (c) Inversion (d) Translocation A deletion removes a chromosomal segment. A duplication repeats a segment. An inversion reverses a segment within a chromosome. A translocation moves a segment from one chromosome to a non-homologous chromosome. A B C D E F G H A B C E F G H A B C D E F G H A B C D E F G HB C A B C D E F G H A D C B E F G H A B C D E F G H M N O P Q R GM N O C HFED A B P Q R 50
  51. 51. Human Disorders Due to Chromosomal Alterations Some types of aneuploidy have higher survival rates, resulting in individuals surviving to birth & beyond These survivors have a set of symptoms (syndrome) characteristic of the type of aneuploidy 51
  52. 52. Down Syndrome (Trisomy 21) Aneuploidy due to 3 copies of chromosome 21 - affects 1 out of every 700-1000 US children - most common chromosomal abnormality in humans - frequency increases with mother’s age (40+ years) - due to nondisjunction in Meiosis I - diagnosed via prenatal screening 52
  53. 53. 53 - Short stature - Heart defects - Developmental delays - Sexually underdeveloped or sterile - Mild/moderate intellectual disability - 50-60 year life expectancy Down Syndrome (Trisomy 21)
  54. 54. Aneuploidy of Sex Chromosomes Due to nondisjunction of sex chromosomes Klinefelter syndrome: results from an extra X chromosome in a male, producing XXY individuals (the extra X chromosome is inactivated) Monosomy X (Turner syndrome): produces sterile X0 females - the only known viable monosomy in humans - reproductive organs don’t mature 54
  55. 55. Klinefelter Syndrome (47, XXY) 55 - 1 in 500-1000 births - Hypogonadism - Sterility - Some have no symptoms - Lots of variations
  56. 56. Turner Syndrome (X0) 56 - 1 in 2500 births - Short stature - Webbed necks - Ovaries non- functional - Sterility - Heart disease - Hypothyroidism
  57. 57. 57 Turner Syndrome: webbed neck
  58. 58. Disorders Caused by Structurally Altered Chromosomes Cri du chat syndrome: due to a specific deletion at the end of chromosome 5 (deletions often cause severe problems) - 1 in 50,000 births - mental retardation, catlike cry - small head with unusual facial features - individuals usually die in infancy or early childhood 58 partial monosomy
  59. 59. Disorders Caused by Structurally Altered Chromosomes Certain cancers are caused by translocations of chromosomes - Chronic myelogenous leukemia (CML) 59 - Abnormal WBC’s accumulate in blood during mitosis of myeloid stem cells in red bone marrow - Cause unknown - Diagnosed in mid-60’s - Higher survival rates - Treated with tyrosine kinase inhibitors (TKI’s)
  60. 60. Normal chromosome 9 Normal chromosome 22 Reciprocal translocation Translocated chromosome 9 Translocated chromosome 22 – much shorter (Philadelphia chromosome): gene activated that causes uncontrolled mitosis in CML patients 60
  61. 61. There are 2 normal exceptions to Mendelian genetics 1. One involves genes located inside the nucleus (genomic imprinting) 2. The other involves genes located outside the nucleus (extranuclear genes) In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance 61
  62. 62. Genomic Imprinting For a few mammalian developmental traits, phenotype depends on which parent passed along those alleles - this phenotype variation is called genomic imprinting - involves the silencing of certain genes that are “stamped” with an imprint during gamete production - due to the methylation (addition of –CH3) of cysteine (C) nucleotides of DNA 62
  63. 63. Normal Igf2 allele is expressed Paternal chromosome Maternal chromosome (a) Homozygote Wild-type mouse (normal size) Normal Igf2 allele is not expressed Genomic imprinting of the mouse Igf2 gene 63
  64. 64. Mutant Igf2 allele inherited from mother Mutant Igf2 allele inherited from father Normal size mouse (wild type) Dwarf mouse (mutant) Normal Igf2 allele is expressed Mutant Igf2 allele is expressed Mutant Igf2 allele is not expressed Normal Igf2 allele is not expressed (b) Heterozygotes 64
  65. 65. Inheritance of Organelle Genes Extranuclear (cytoplasmic) genes: found in organelles in the cytoplasm - mitochondria, chloroplasts, & other plant plastids carry small circular DNA molecules - extranuclear genes are inherited maternally because the zygote’s cytoplasm comes from the egg - the first evidence came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant 65
  66. 66. 66
  67. 67. Some defects in mitochondrial genes prevent normal ATP synthesis - result in diseases that affect the muscular & nervous systems - Mitochondrial myopathy 67
  68. 68. 68