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PowerPoint to accompany Genetics: From Genes to Genomes Fourth Edition Leland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M.

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Presentation on theme: "PowerPoint to accompany Genetics: From Genes to Genomes Fourth Edition Leland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M."— Presentation transcript:

1 PowerPoint to accompany Genetics: From Genes to Genomes Fourth Edition Leland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M. Silver Prepared by Mary A. Bedell University of Georgia 1 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition

2 How Genes Travel on Chromosomes 2 PART IV Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 Chromosomal Rearrangements and Changes in Chromosome Number 13.1 Rearrangements of DNA Sequences 13.2 Transposable Genetic Elements 13.3 Rearrangements and Evolution: A Speculative Comprehensive Example 13.4 Changes in Chromosome Number 13.5 Emergent Technologies: Beyond the Karyotype CHAPTER OUTLINE CHAPTERCHAPTER

3 Two main themes underlying the observations on chromosomal changes 1. Karyotypes generally remain constant within a species Most genetic imbalances result in a selective disadvantage 2. Related species usually have different karyotypes Closely-related species differ by only a few rearrangements Distantly-related species differ by many rearrangements Correlation between karyotypic rearrangements and speciation Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 3

4 Chromosomal rearrangements Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 4 Table 13.1

5 Changes in chromosome number Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 5 Table 13.1 (cont)

6 Deletions: origin and detection Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 6 Fig. 13.2 Symbols for a deletion are Del or Df (i.e. Del/+ or Df/+ is a deletion heterozygote and Del/Del or Df/Df is a deletion homozygote)

7 Heterozygosity for deletions may have phenotypic consequences With some genes, an abnormal phenotype can be caused by an imbalance in gene dosage (i.e. 2 copies vs. 1 copy of an autosomal gene) In humans, deletion heterozygotes with loss of >3% of genome are not viable Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 7 Fig. 13.3

8 Deletion loops form in the chromosomes of deletion heterozygotes Recombination between homologs can occur only at regions of similarity No recombination can occur within a deletion loop Consequently, genetic map distances in deletion heterozygotes will not be accurate Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 8 Fig. 13.4

9 In deletion heterozygotes, pseudodominance can "uncover" a recessive mutation Similar to a complementation test Examine phenotype of a heterozygote for recessive allele and deletion: If the phenotype is mutant, the mutant gene must lie inside the deleted region If the phenotype is wild-type, the mutant gene must lie outside the deleted region Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 9 Fig. 13.5

10 Polytene chromosomes in the salivary glands of Drosophila larvae In Drosophila, interphase chromosomes replicate 10 times without going through mitosis Each chromosome has 2 10 double helices Banding patterns are reproducible and provide detailed physical guide to gene mapping Total ~5000 bands, size of each band is 3-150 kb Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 10 Fig. 13.6a

11 Deletion loops also form in polytene chromosomes of Drosophila deletion heterozygotes In Drosophila, homologous chromosomes pair with each other during interphase Comparison of banding patterns in polytene chromosomes of a deletion heterozygote can reveal the position of deletion Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 11 Fig. 13.7

12 Using deletions to assign genes to bands on Drosophila polytene chromosomes Complementation tests with several deletions used to determine the locations of white (w), roughest (rst), and facet (fa) genes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 12 Fig. 13.8

13 In situ hybridization as a tool for locating genes at the molecular level A DNA probe containing the white gene hybridizes to the tip of the Drosophila wild-type polytene X chromosome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 13 Fig. 13.9a

14 Characterizing deletions with in situ hybridization to polytene chromosomes Labeled DNA probe hybridizes to the wild-type chromosome but not to the deletion chromosome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 14 Fig. 13.9b

15 Diagnosing DiGeorge syndrome by fluorescence in situ hybridization (FISH) DiGeorge syndrome in humans: Accounts for 5% of all congenital heart defects Affected people are heterozygous for a 22q11 deletion Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 15 Fig. 13.10 FISH on human metaphase chromosomes Green dots; control probe for chromosome 22 Red dot; probe from 22q11 region

16 Summary of phenotypic and genetic effects of deletions Homozygosity or heterozygosity for deletions can be lethal or harmful Depends on size of deletions and affected genes In deletion heterozygotes, deletions reveal the effects of recessive mutations Deletions can be used to map and identify genes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 16

17 Types of duplications (Dp) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 17 Fig. 13.11a

18 Chromosome breakage can produce duplications According to one scenario, nontandem duplications could be produced by insertion of a fragment elsewhere on the homologous chromosome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 18 Fig. 13.11b

19 Different kinds of duplication loops in duplication heterozygotes (Dp/+) Different configurations can occur in prophase I of meiosis Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 19 Fig. 13.11c

20 Duplication heterozygosity can cause visible phenotypes Increased gene dosage can result in a mutant phenotype Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 20 Fig. 13.12a

21 For rare genes, survival requires exactly two copies Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 21 Fig. 13.12b

22 Unequal crossing-over can increase or decrease copy number Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 22 Fig. 13.13 Genotype of X chromosome Out-of-register pairing during meiosis can occur in a Bar-eyed female Phenotype

23 Summary of phenotypic and genetic effects of duplications Novel phenotypes may occur because of increased gene copy number or because of altered expression in new chromosomal environment Homozygosity or heterozygosity for a duplication can be lethal or harmful Depends on size of duplication and affected genes Unequal crossing-over between duplicated regions on homologous chromosomes can result in increased and decreased copy number Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 23

24 Chromosome breakage can produce inversions (In) Pericentric inversion – centromere is within the inverted segment Paracentric inversion – centromere is not within the inverted segment Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 24 Fig. 13.14a

25 Intrachromosomal recombination can also produce inversions Recombination occurs between related sequences that are in opposite orientations on the same chromosome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 25 Fig. 13.14b

26 Phenotypic effects of inversions Most inversions do not result in an abnormal phenotype Abnormal phenotypes can occur if: Inversion disrupts a gene (Fig. 13.14c) Inversion places a gene in chromosomal environment that alters its expression i.e. Gene is placed near regulatory sequences for other genes or near heterochromatin (PEV, chapter 12) Inversions can act as crossover suppressors In inversion heterozygotes, no viable offspring are produced that carry chromosomes resulting from recombination in inverted region Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 26

27 Inversions can disrupt a gene Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 27 Fig. 13.14c

28 Inversion loops form in inversion heterozygotes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 28 Fig. 13.15 Formation of inversion loop allows tightest possible alignment of homologous regions Crossing over within the inversion loop produces aberrant recombinant chromatids

29 Why pericentric inversion heterozygotes produce few if any recombinant progeny Each recombinant chromatid has a centromere, but each will be genetically unbalanced Zygotes formed from union of normal gametes with gametes carrying these recombinant chromatids will be nonviable Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 29 Fig. 13.16a

30 Why paracentric inversion heterozygotes produce few if any recombinant progeny One recombinant chromatid lacks a centromere and the other recombinant chromatid has two centromeres Zygotes formed from union of normal gametes with gametes carrying the broken dicentric recombinant chromatids will be nonviable Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 30 Fig. 13.16b

31 Balancer chromosomes are useful tools for genetic analysis Balancer chromosomes have a dominant visible marker and multiple, overlapping inversions In progeny of crosses of heterozygotes with a marked balancer and a non-inversion chromosome No viable progeny with recombinants on this chromosome will be produced because of crossover suppression Progeny that don't carry the marked chromosome must carry the nonrecombined, unmarked chromosome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 31 Fig. 13.17 Balancer chromosome Normal chromosome with mutations of interest

32 Summary of phenotypic and genetic effects of inversions Inversions don't add or remove DNA, but can disrupt a gene or alter expression of a gene In inversion heterozygotes, recombination within inverted segment results in genetically unbalanced gametes Balancer chromosomes with inversions are useful genetic tools Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 32

33 Translocations attach part of one chromosome to another chromosome Reciprocal translocation (Fig. 13.18) Two different chromosomes each have a chromosome break Reciprocal exchange of fragments – each fragment replaces the fragment on the other chromosome Robertsonian translocation (Fig. 13.19) Chromosomal breaks occur at or near centromeres of two acrocentric chromosomes Generates one large metacentric chromosome and one small chromosome, which is usually lost Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 33

34 Two chromosome breaks can produce a reciprocal translocation Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 34 Fig. 13.18a

35 Chromosome painting reveals a reciprocal translocation Translocated chromosomes are stained red and green Non-translocated chromosomes are stained entirely red or entirely green Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 35 Fig. 13.18b

36 Robertsonian translocations can reshape genomes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 36 Fig. 13.19

37 Phenotypic effects of reciprocal translocations Most reciprocal translocations don't affect the phenotype because they don't add or remove DNA Abnormal phenotypes can be caused if translocation breakpoint disrupts a gene or results in altered expression of a gene Translocations in somatic cells can result in oncogene activation (Fig. 13.20) Defects that are observed in translocation heterozygotes Unbalanced gametes are produced, which results in reduced fertility (Fig. 13.21) Genetic map distance are altered because of pseudolinkage Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 37

38 A reciprocal translocation is the basis for chronic myelogenous leukemia Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 38 Fig. 13.20b

39 In a translocation homozygote, chromosomes segregate normally during meiosis I If the breakpoints of a reciprocal translocation do not affect gene function, there are no genetic consequences in homozygotes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 39 Fig. 13.21a

40 Chromosome pairing in a translocation heterozygote In a translocation heterozygote, the two haploid sets of chromosomes carry different arrangements of DNA Chromosome pairing during prophase I of meiosis is maximized by formation of a cruciform structure Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 40 Three segregation patterns are possible (Fig. 13.21c) Fig. 13.21b

41 Three chromosome segregation patterns are possible in a translocation heterozygote Balanced gametes are produced only by alternate segregation, and not by adjacent-1 or adjacent-2 segregation Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 41 Fig. 13.21 c

42 Semisterility in a corn plant that is heterozygous for a reciprocal translocation Slightly less than 50% of gametes arise from alternate segregation and are viable Unbalanced ovules resulting from adjacent-1 or adjacent-2 segregation are aborted Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 42 Fig. 13.21d

43 Pseudolinkage is observed in heterozygotes with reciprocal translocations In non-translocation heterozygotes, there are only two possible segregation patterns With all offspring viable, Mendel's law of independent assortment would be observed with unlinked genes In a reciprocal translocation heterozygote, only the alternate segregation pattern results in viable progeny In outcrosses, genes located on the nonhomologous chromosomes would behave as if they are linked Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 43

44 Down syndrome arising from a Robertsonian translocation between chromosomes 21 and 14 14q21q translocation heterozygote Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 44 Fig. 13.22 Three chromosome segregation patterns

45 Transposable elements (TEs) are movable genetic elements TEs are any segment of DNA that evolves the ability to move from place to place within a genome Marcus Rhoades (1930s) and Barbara McClintock (1950s) inferred existence of TEs from genetic studies of corn TEs have now been found in all organisms Previously considered to be selfish DNA – carried no genetic information useful to host Now known that some TEs have evolved functions that are beneficial to host TE length ranges from 50 bp to 10 kb TEs can be present in hundreds of thousands of copies per genome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 45

46 Barbara McClintock: Discoverer of transposable elements Received Nobel Prize in 1983 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 46 Fig. 13.23

47 TEs can move to many locations in a genome In situ hybridization for the copia TE in Drosophila Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 47 Fig. 13.24

48 Mammals have two major classes of TEs Long interspersed elements (LINEs) Main LINE in humans is L1 Up to 6.4 kb in length 20,000 copies in human genome Short, interspersed elements (SINEs) Main SINE in humans is Alu 0.28 kb in length 300,000 copies in human genome, dispersed at ~ 10 kb intervals L1 and Alu sequences make up 7% of the human genome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 48

49 TEs in the corn genome Mottling of kernels caused by movements of a TE into and out of a pigment gene Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 49 Fig. 13.25b

50 Two groups of TEs Retroposons Move via reverse transcription of an RNA intermediate e.g. copia elements in Drosophila, L1 and Alu in humans Transposons Move directly without being transcribed into RNA e.g. TEs studied by McClintock in corn, P elements in Drosophila Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 50

51 Two kinds of retroposons Both types carry a gene for reverse transcriptase Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 51 Fig. 13.26a Has long terminal repeats (LTRs) oriented in the same direction on either side of element Has polyA tail at 3'end of an RNA-like DNA strand

52 Experiment done with Ty1 retroposon of yeast Ty1 with an intron cloned into a plasmid All new insertions of this Ty1 into the yeast genome lacked the intron The intron must have been removed by splicing from an RNA Evidence that retroposons move via RNA intermediates Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 52 Fig. 13.26b

53 How retroposons move Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 53 Reverse transcriptase makes a double-stranded retroposon cDNA Staggered cut is made in genomic target site Retroposon cDNA inserts into target site Sticky ends of target site are filled in, creating two copies of the 5 bp target site Original copy remains while new copy inserts into another genomic location Fig. 13.26c

54 Transposon structure Most transposons contain: Inverted repeats (IRs) of 10-200 bp long at each end Gene encoding transposase, which recognizes the IRs and cuts at border between the IR and genomic DNA Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 54 Fig. 13.27a

55 P elements in Drosophila melanogaster Most laboratory strains of D. melanogaster are M strains Isolated in early 1900s Have no P elements Natural populations of D. melanogaster are P strains Isolated since 1950 Have many copies of P elements Hybrid dysgenesis - cross P male with M female Offspring are sterile, have high levels of mutation, and chromosome breaks Elevated levels of P element transposition Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 55

56 How P element transposons move Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 56 Fig. 13.27b

57 Genomes often contain defective copies of TEs Many TEs sustain deletions during the process of transposition or after transposition Deletion of promoter for retroposon transcription Deletion of reverse transcriptase gene or transposase gene Deletion of IRs Most SINEs and LINEs in human genome are defective Autonomous TEs – nondeleted TEs that can transpose on their own Nonautonomous TEs – defective TEs that can transpose only if transposase activity expressed from intact TE Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 57

58 TEs can disrupt genes and alter genomes TE insertion can result in altered phenotype TE can insert within coding region of a gene TE can insert near a gene and affect its expression Examples: Drosophila white gene (Fig. 13.28), wrinkled peas studied by Mendel, hemophilia in humans caused by Alu insertion into clotting factor IX TEs can trigger spontaneous chromosomal rearrangements Unequal crossing over between TEs (Fig. 13.29a) Gene relocation due to transposition Formation of composite TE (Fig. 13.29b) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 58

59 Spontaneous mutations in the white gene of Drosophila arising from TE insertions Eye color phenotype depends on the TE involved (pogo, copia, roo, and Doc) and where it inserts Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 59 Fig. 13.28

60 Unequal crossing-over between TEs Can occur between TEs found in slightly different locations on homologous chromosomes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 60 Fig. 13.29a

61 Two transposons can form a large, composite transposon Composite transposons Can occur when two copies of a TE integrate in nearby locations on the same chromosome Transposase can recognize outermost IR sequences and move intervening sequences to a different location Can move up to 400 kb of DNA Mediates transfer of drug resistance genes between different strains and species of bacteria (discussed in Chapter 14) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 61 Fig. 13.29b

62 Rearrangements and evolution: A speculative comprehensive example Deletions May move the coding region of one gene closer to regulatory sequences of another gene Timing or tissue-specificity of expression may be altered Duplications One copy of the gene retains original function and the new copy evolves new functions Generation of multi-gene families Inversions Crossover suppression can ensure that beneficial alleles of closely-linked genes do not separate by recombination Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 62

63 Rearrangements and evolution: A speculative comprehensive example (cont) Translocations Robertsonian translocations can lead to reproductive isolation and speciation e.g. Two populations of mice on the island of Madeira (Fig. 13.30) Transpositions Create novel mutations, duplications, inversions that affect gene functions in beneficial ways Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 63

64 Rapid chromosomal evolution in house mice on the island of Madeira One population of mice introduced to island in 1400s Two populations evolved different sets of Robertsonian translocations, hybrid offspring are sterile Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 64 Fig. 13.30

65 Aneuploidy is the loss or gain of one or more chromosomes Aneuploids – individuals whose chromosome number is not an exact multiple of the haploid number (n) for that species Monosomic – individuals that lack one chromosome from the normal diploid number (2n – 1) Trisomic – individuals that have one chromosome in addition to the normal diploid number (2n + 1) Tetrasomic – organisms with four copies of a particular chromosome (2n + 2) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 65

66 Deleterious effects of autosomal aneuploidy in humans Most autosomal aneuploidies and trisomies are lethal and result in spontaneous abortion Trisomy 21 (Down syndrome) is the most frequently observed autosomal trisomy Majority of Down syndrome results from nondisjunction during maternal meiosis I (Fig. 13.32a) Individuals with monosomy 21 survive for only a short time after birth Two autosomal trisomies allow birth, but cause severe developmental abnormalities and early death Trisomy 18 causes Edwards syndrome Trisomy 13 cause Patau syndrome Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 66

67 X chromosome aneuploidies X-inactivation results in dosage compensation for most genes on the X chromosome Some genes on X chromosome escape inactivation X reactivation occurs in oogonia so that every mature ovum receives an active X XXY individuals – Klinefelter syndrome (see Fig. 13.31) Some X-linked genes expressed at twice the normal level and result in skeletal abnormalities, long limbs, and sterility XO individuals – Turner syndrome Sterility may be caused by decreased dosage of X-linked genes in oogonia Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 67

68 Humans tolerate X chromosome aneuploidy because of X inactivation Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 68 Fig. 13.31

69 Aneuploidy is caused by nondisjunction Nondisjunction is the failure of chromosomes to segregate normally and can occur during either meiosis I or meiosis II Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 69 Fig. 13.32a

70 Aneuploids beget aneuploid progeny Offspring of fertile aneuploids have an extremely high chance of aneuploidy because of production of unbalanced gametes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 70 Fig. 13.32b

71 Mistakes in chromosome segregation can occur in somatic cells Mitotic nondisjunction – failure of sister chromatids to separate during anaphase of mitosis Chromosome loss – lagging chromatid that is not pulled to either spindle pole at mitotic anaphase Mosaic organism Aneuploid cells can survive and undergo further rounds of mitosis, producing clones of aneuploid cells Side-by-side existence of aneuploid and normal tissues e.g. Mitotic nondisjunction of X chromosome Gynandromorphs in XX Drosophila (Fig. 13.33c) Some cases of Turner and Down syndrome in humans Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 71

72 Nondisjunction during mitosis can generate clones of aneuploid cells Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 72 Fig. 13.33

73 Some euploid species are not diploid Euploids carry complete sets of chromosomes Polyploids – carry 3 complete sets of chromosomes Monoploids – 1x, carry only one set of chromosomes Triploids – 3x, three complete sets of chromosomes Tetraploids – 4x, four complete sets of chromosomes Monoploidy and polyploidy rarely observed in animals Exceptions – in some species of ants and bees, males are monoploid and females are diploid; hermaphroditic worms are polyploid; some fish are tetraploid Polyploidy in humans is lethal Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 73

74 Chromosome numbers x = the number of different chromosomes that make up a single, complete set n = number of chromosomes in gametes In diploids, x = n For polyploids, x n (e.g. bread wheat is hexaploid, x = 7, 6x = 42, n = 21) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 74

75 Creation and use of monoploid plants Creation of monoploid plants (see Fig. 13.34a): Special treatment of germ cells from diploid species Rare spontaneous events in large, natural populations Usually sterile, but can easily be converted to diploid (Fig. 13.34c) Uses of monoploid plants (see Fig. 13.34b): Can visualize recessive traits directly, without crosses to homozygosity Introduce mutations into individual monoploid cells Select for desirable phenotypes (herbicide resistance) Hormone treatment to grow cells into monoploid plants Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 75

76 The creation and use of monoploid plants Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 76 Fig. 13.34

77 Colchicine treatment prevents spindle formation and results in doubling of chromosome numbers Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 77 Fig. 13.34c

78 Formation of a triploid organism Diploid gametes may arise from 4x parent or from a diploid with defects in meiosis (defect in spindle or defect at cytokinesis) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 78 Fig. 13.35a

79 Meiosis in a triploid organism Regardless of how chromosomes pair, there is no way to ensure that gametes contain a complete balanced set of chromosomes All polyploids with odd numbers of chromosome sets are sterile because they cannot produce balanced gametes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 79 Fig. 13.35b

80 Generation of tetraploid (4x) cells Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 80 Tetraploid cells occur during mitosis in a diploid when chromosomes fail to separate into two daughter cells If tetraploidy occurs in gamete precursors, diploid gametes are produced Union of two diploid gametes produces a tetraploid organism Autopolyploid – all chromosome sets are derived from the same species Fig. 13.36a

81 In a tetraploid, pairing of chromosomes as bivalents generates balanced gametes Four copies of each group of homologs pair two-by-two to form two bivalents Successful tetraploids produce balanced 2X gametes and are fertile Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 81 Fig. 13.36b

82 Gametes formed by A A a a tetraploids Tetraploids generate unusual Mendelian ratios Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 82 Fig. 13.36c

83 Polyploids in agriculture One-third of all known flowering plant species are polyploid Polyploidy often results in increased size and vigor Many polyploid plants have been selected for agricultural cultivation Tetraploids – alfalfa, coffee, peanuts, Macintosh apples, Bartlett pear Octaploids – strawberries (Fig. 13.37) Allopolyploid – hybrids in which chromosome sets come from distinct, but related, species Amphidiploid – has two diploid parental species e.g. Raphanobrassica – sterile F 1 from crossing cabbages and radishes, has 18 chromosomes (9 from each parent) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 83

84 Creation of the allopolyploid Triticale F1 hybrid of wheat and rye is sterile because there are no pairing partners for the rye chromosomes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 84 Fig. 13.38a

85 Fertile Triticale can be created from infertile F1 hybrid Triticale Different Triticale hybrids have been generated Some combine high yield of wheat with ability of rye to grow in unfavorable enviroments Some combine high level of protein from wheat with high level of lysine from rye Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 85 Fig. 13.38a (cont)

86 Emergent technologies: Beyond the karyotype Two main problems with traditional karyotyping Procedure is tedious and microscopic analysis is subjective Very low resolution – cannot detect deletions or duplications of < 5 Mb Development of microarray-based technologies Can scan entire genome for chromosomal rearrangements and aneuploidy Has much higher accuracy, resolution, and throughput Comparative genomic hybridization (Fig. 13.39) Also called "virtual karyotyping" Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 86

87 Preparation of microarray and samples for comparative genomic hybridization (CGH) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 87 Fig. 13.39

88 Detection of duplications and deletions by CGH After hybridization of DNA samples, analyze microarray for ratio of yellow (control DNA) and orange (test DNA) Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 88 (c) Incubate microarray with combined samples Fig. 13.39

89 Aneuploidy in the human population Incidence of abnormal phenotypes caused by aberrant chromosome organization or number is 0.004% Half of spontaneously aborted fetuses have chromosome abnormalities Incidence of abnormal phenotypes caused by single-gene mutations is 0.010% Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13 89 Table 13.2


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