Genetics: From genes to genomes - Chapter 13: How genes travel on chromosomes

PowerPoint to accompanyGenetics: From Genes to GenomesFourth EditionLeland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M. SilverPrepared by Mary A. BedellUniversity of Georgia*Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th editionHow Genes Travel on Chromosomes*PART IVCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13Chromosomal Rearrangements and Changes in Chromosome Number13.1 Rearrangements of DNA Sequences13.2 Transposable Genetic Elements13.3 Rearrangements and Evolution: A Speculative Comprehensive Example13.4 Changes in Chromosome Number13.5 Emergent Technologies: Beyond the KaryotypeCHAPTER OUTLINECHAPTERTwo main themes underlying the observations on chromosomal changesKaryotypes generally remain constant within a speciesMost genetic imbalances result in a selective disadvantageRelated species usually have different karyotypesClosely-related species differ by only a few rearrangementsDistantly-related species differ by many rearrangementsCorrelation between karyotypic rearrangements and speciationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Chromosomal rearrangementsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Table 13.1Changes in chromosome numberCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Table 13.1 (cont)Deletions: origin and detectionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.2Symbols 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)Heterozygosity for deletions may havephenotypic consequencesWith 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 viableCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.3Deletion loops form in the chromosomesof deletion heterozygotesRecombination between homologs can occur only at regions of similarityNo recombination can occur within a deletion loopConsequently, genetic map distances in deletion heterozygotes will not be accurateCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.4In deletion heterozygotes, pseudodominancecan "uncover" a recessive mutationSimilar to a complementation testExamine phenotype of a heterozygote for recessive allele and deletion:If the phenotype is mutant, the mutant gene must lie inside the deleted regionIf the phenotype is wild-type, the mutant gene must lie outside the deleted regionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.5Polytene chromosomes in the salivaryglands of Drosophila larvaeIn Drosophila, interphase chromosomes replicate 10 times without going through mitosisEach chromosome has 210 double helicesBanding patterns are reproducible and provide detailed physical guide to gene mappingTotal ~5000 bands, size of each band is 3-150 kbCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.6aDeletion loops also form in polytene chromosomes of Drosophila deletion heterozygotesIn Drosophila, homologous chromosomes pair with each other during interphaseComparison of banding patterns in polytene chromosomes of a deletion heterozygote can reveal the position of deletionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.7Using deletions to assign genes to bandson Drosophila polytene chromosomesComplementation tests with several deletions used to determine the locations of white (w), roughest (rst), and facet (fa) genesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.8In situ hybridization as a tool for locatinggenes at the molecular levelA DNA probe containing the white gene hybridizes to the tip of the Drosophila wild-type polytene X chromosomeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.9aCharacterizing deletions with in situ hybridization to polytene chromosomesLabeled DNA probe hybridizes to the wild-type chromosome but not to the deletion chromosomeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.9bDiagnosing DiGeorge syndrome byfluorescence in situ hybridization (FISH)DiGeorge syndrome in humans:Accounts for 5% of all congenital heart defectsAffected people are heterozygous for a 22q11 deletionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.10FISH on human metaphase chromosomesGreen dots; control probe for chromosome 22Red dot; probe from 22q11 regionSummary of phenotypic and genetic effects of deletionsHomozygosity or heterozygosity for deletions can be lethal or harmfulDepends on size of deletions and affected genesIn deletion heterozygotes, deletions reveal the effects of recessive mutationsDeletions can be used to map and identify genesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Types of duplications (Dp)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.11aChromosome breakage can produce duplicationsAccording to one scenario, nontandem duplications could be produced by insertion of a fragment elsewhere on the homologous chromosomeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.11bDifferent kinds of duplication loops in duplication heterozygotes (Dp/+)Different configurations can occur in prophase I of meiosisCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.11cDuplication heterozygosity can cause visible phenotypesIncreased gene dosage can result in a mutant phenotypeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.12aFor rare genes, survival requires exactly two copiesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.12bUnequal crossing-over can increase ordecrease copy numberCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.13Genotype of X chromosomeOut-of-register pairing during meiosis can occur in a Bar-eyed femalePhenotypeSummary of phenotypic and genetic effects of duplicationsNovel phenotypes may occur because of increased gene copy number or because of altered expression in new chromosomal environmentHomozygosity or heterozygosity for a duplication can be lethal or harmfulDepends on size of duplication and affected genesUnequal 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*Chromosome breakage can produce inversions (In)Pericentric inversion – centromere is within the inverted segmentParacentric inversion – centromere is not within the inverted segmentCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.14aIntrachromosomal recombination can also produce inversionsRecombination occurs between related sequences that are in opposite orientations on the same chromosomeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.14bPhenotypic effects of inversionsMost inversions do not result in an abnormal phenotypeAbnormal phenotypes can occur if:Inversion disrupts a gene (Fig. 13.14c)Inversion places a gene in chromosomal environment that alters its expressioni.e. Gene is placed near regulatory sequences for other genes or near heterochromatin (PEV, chapter 12)Inversions can act as crossover suppressorsIn inversion heterozygotes, no viable offspring are produced that carry chromosomes resulting from recombination in inverted regionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Inversions can disrupt a geneCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.14cInversion loops form in inversion heterozygotesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.15Formation of inversion loop allows tightest possible alignment of homologous regionsCrossing over within the inversion loop produces aberrant recombinant chromatidsWhy pericentric inversion heterozygotes produce few if any recombinant progenyEach recombinant chromatid has a centromere, but each will be genetically unbalancedZygotes formed from union of normal gametes with gametes carrying these recombinant chromatids will be nonviableCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.16aWhy paracentric inversion heterozygotes produce few if any recombinant progenyOne recombinant chromatid lacks a centromere and the other recombinant chromatid has two centromeresZygotes formed from union of normal gametes with gametes carrying the broken dicentric recombinant chromatids will be nonviableCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.16bBalancer chromosomes are useful toolsfor genetic analysisBalancer chromosomes have a dominant visible marker and multiple, overlapping inversionsIn progeny of crosses of heterozygotes with a marked balancer and a non-inversion chromosomeNo 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 chromosomeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.17Balancer chromosomeNormal chromosome with mutations of interestSummary of phenotypic and genetic effects of inversionsInversions don't add or remove DNA, but can disrupt a gene or alter expression of a geneIn inversion heterozygotes, recombination within inverted segment results in genetically unbalanced gametesBalancer chromosomes with inversions are useful genetic toolsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Translocations attach part of one chromosome to another chromosomeReciprocal translocation (Fig. 13.18)Two different chromosomes each have a chromosome breakReciprocal exchange of fragments – each fragment replaces the fragment on the other chromosomeRobertsonian translocation (Fig. 13.19)Chromosomal breaks occur at or near centromeres of two acrocentric chromosomesGenerates one large metacentric chromosome and one small chromosome, which is usually lostCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Two chromosome breaks can produce a reciprocal translocationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.18aChromosome painting reveals a reciprocal translocationTranslocated chromosomes are stained red and greenNon-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*Fig. 13.18bRobertsonian translocations can reshape genomesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.19Phenotypic effects of reciprocal translocationsMost reciprocal translocations don't affect the phenotype because they don't add or remove DNAAbnormal phenotypes can be caused if translocation breakpoint disrupts a gene or results in altered expression of a geneTranslocations 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 pseudolinkageCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*A reciprocal translocation is the basis for chronic myelogenous leukemiaCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.20bIn a translocation homozygote, chromosomes segregate normally during meiosis IIf the breakpoints of a reciprocal translocation do not affect gene function, there are no genetic consequences in homozygotesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.21aChromosome pairing in a translocation heterozygoteIn a translocation heterozygote, the two haploid sets of chromosomes carry different arrangements of DNAChromosome pairing during prophase I of meiosis is maximized by formation of a cruciform structureCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Three segregation patterns are possible (Fig. 13.21c)Fig. 13.21bThree chromosome segregation patterns are possible in a translocation heterozygoteBalanced gametes are produced only by alternate segregation, and not by adjacent-1 or adjacent-2 segregationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.21cSemisterility in a corn plant that is heterozygous for a reciprocal translocationSlightly less than 50% of gametes arise from alternate segregation and are viableUnbalanced ovules resulting from adjacent-1 or adjacent-2 segregation are abortedCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.21dPseudolinkage is observed in heterozygotes with reciprocal translocationsIn 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 genesIn a reciprocal translocation heterozygote, only the alternate segregation pattern results in viable progenyIn outcrosses, genes located on the nonhomologous chromosomes would behave as if they are linkedCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Down syndrome arising from a Robertsonian translocation between chromosomes 21 and 1414q21q translocation heterozygoteCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.22Three chromosome segregation patterns Transposable elements (TEs) are movable genetic elementsTEs are any segment of DNA that evolves the ability to move from place to place within a genomeMarcus Rhoades (1930s) and Barbara McClintock (1950s) inferred existence of TEs from genetic studies of cornTEs have now been found in all organismsPreviously considered to be selfish DNA – carried no genetic information useful to hostNow known that some TEs have evolved functions that are beneficial to hostTE length ranges from 50 bp to 10 kbTEs can be present in hundreds of thousands of copies per genomeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Barbara McClintock: Discoverer oftransposable elementsReceived Nobel Prize in 1983Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.23TEs can move to many locations in a genomeIn 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*Fig. 13.24Mammals have two major classes of TEsLong interspersed elements (LINEs)Main LINE in humans is L1Up to 6.4 kb in length20,000 copies in human genomeShort, interspersed elements (SINEs)Main SINE in humans is Alu0.28 kb in length300,000 copies in human genome, dispersed at ~ 10 kb intervalsL1 and Alu sequences make up 7% of the human genomeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*TEs in the corn genomeMottling of kernels caused by movements of a TE into and out of a pigment geneCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.25bTwo groups of TEsRetroposonsMove via reverse transcription of an RNA intermediatee.g. copia elements in Drosophila, L1 and Alu in humansTransposonsMove directly without being transcribed into RNAe.g. TEs studied by McClintock in corn, P elements in DrosophilaCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Two kinds of retroposonsBoth types carry a gene for reverse transcriptaseCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.26aHas long terminal repeats (LTRs) oriented in the same direction on either side of elementHas polyA tail at 3'end of an RNA-like DNA strandExperiment done with Ty1 retroposon of yeastTy1 with an intron cloned into a plasmidAll new insertions of this Ty1 into the yeast genome lacked the intronThe intron must have been removed by splicing from an RNAEvidence that retroposons move via RNA intermediatesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.26bHow retroposons moveCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Reverse transcriptase makes a double-stranded retroposon cDNAStaggered cut is made in genomic target siteRetroposon cDNA inserts into target siteSticky 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 locationFig. 13.26cTransposon structureMost transposons contain:Inverted repeats (IRs) of 10-200 bp long at each endGene encoding transposase, which recognizes the IRs and cuts at border between the IR and genomic DNACopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.27aP elements in Drosophila melanogasterMost laboratory strains of D. melanogaster are M strains Isolated in early 1900sHave no P elementsNatural populations of D. melanogaster are P strainsIsolated since 1950 Have many copies of P elementsHybrid dysgenesis - cross P male with M femaleOffspring are sterile, have high levels of mutation, and chromosome breaksElevated levels of P element transposition Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*How P element transposons moveCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.27bGenomes often contain defective copies of TEsMany TEs sustain deletions during the process of transposition or after transpositionDeletion of promoter for retroposon transcriptionDeletion of reverse transcriptase gene or transposase geneDeletion of IRs Most SINEs and LINEs in human genome are defectiveAutonomous TEs – nondeleted TEs that can transpose on their ownNonautonomous TEs – defective TEs that can transpose only if transposase activity expressed from intact TECopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*TEs can disrupt genes and alter genomesTE insertion can result in altered phenotypeTE can insert within coding region of a geneTE can insert near a gene and affect its expressionExamples: Drosophila white gene (Fig. 13.28), wrinkled peas studied by Mendel, hemophilia in humans caused by Alu insertion into clotting factor IXTEs can trigger spontaneous chromosomal rearrangementsUnequal crossing over between TEs (Fig. 13.29a)Gene relocation due to transpositionFormation 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*Spontaneous mutations in the white gene of Drosophila arising from TE insertionsEye 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*Fig. 13.28Unequal crossing-over between TEsCan occur between TEs found in slightly different locations on homologous chromosomesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.29aTwo transposons can form a large, composite transposonComposite transposons Can occur when two copies of a TE integrate in nearby locations on the same chromosomeTransposase can recognize outermost IR sequences and move intervening sequences to a different locationCan move up to 400 kb of DNAMediates 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*Fig. 13.29bRearrangements and evolution: A speculative comprehensive exampleDeletionsMay move the coding region of one gene closer to regulatory sequences of another geneTiming or tissue-specificity of expression may be alteredDuplicationsOne copy of the gene retains original function and the new copy evolves new functionsGeneration of multi-gene familiesInversionsCrossover suppression can ensure that beneficial alleles of closely-linked genes do not separate by recombinationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Rearrangements and evolution: A speculative comprehensive example (cont)TranslocationsRobertsonian translocations can lead to reproductive isolation and speciation e.g. Two populations of mice on the island of Madeira (Fig. 13.30)TranspositionsCreate 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*Rapid chromosomal evolution in housemice on the island of MadeiraOne population of mice introduced to island in 1400sTwo populations evolved different sets of Robertsonian translocations, hybrid offspring are sterileCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.30Aneuploidy is the loss or gain of one or more chromosomesAneuploids – individuals whose chromosome number is not an exact multiple of the haploid number (n) for that speciesMonosomic – 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*Deleterious effects of autosomal aneuploidy in humansMost autosomal aneuploidies and trisomies are lethal and result in spontaneous abortionTrisomy 21 (Down syndrome) is the most frequently observed autosomal trisomyMajority of Down syndrome results from nondisjunction during maternal meiosis I (Fig. 13.32a)Individuals with monosomy 21 survive for only a short time after birthTwo autosomal trisomies allow birth, but cause severe developmental abnormalities and early deathTrisomy 18 causes Edwards syndrome Trisomy 13 cause Patau syndromeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*X chromosome aneuploidiesX-inactivation results in dosage compensation for most genes on the X chromosomeSome genes on X chromosome escape inactivationX reactivation occurs in oogonia so that every mature ovum receives an active XXXY 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 sterilityXO individuals – Turner syndromeSterility may be caused by decreased dosage of X-linked genes in oogoniaCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Humans tolerate X chromosome aneuploidy because of X inactivationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.31Aneuploidy is caused by nondisjunctionNondisjunction is the failure of chromosomes to segregate normally and can occur during either meiosis I or meiosis IICopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.32aAneuploids beget aneuploid progenyOffspring of fertile aneuploids have an extremely high chance of aneuploidy because of production of unbalanced gametesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.32bMistakes in chromosome segregation can occur in somatic cellsMitotic nondisjunction – failure of sister chromatids to separate during anaphase of mitosisChromosome loss – lagging chromatid that is not pulled to either spindle pole at mitotic anaphaseMosaic organismAneuploid cells can survive and undergo further rounds of mitosis, producing clones of aneuploid cellsSide-by-side existence of aneuploid and normal tissuese.g. Mitotic nondisjunction of X chromosomeGynandromorphs in XX Drosophila (Fig. 13.33c)Some cases of Turner and Down syndrome in humansCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Nondisjunction during mitosis can generate clones of aneuploid cellsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.33Some euploid species are not diploidEuploids carry complete sets of chromosomesPolyploids – carry ≥ 3 complete sets of chromosomesMonoploids – 1x, carry only one set of chromosomesTriploids – 3x, three complete sets of chromosomesTetraploids – 4x, four complete sets of chromosomesMonoploidy and polyploidy rarely observed in animalsExceptions – in some species of ants and bees, males are monoploid and females are diploid; hermaphroditic worms are polyploid; some fish are tetraploidPolyploidy in humans is lethalCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Chromosome numbersx = the number of different chromosomes that make up a single, complete setn = number of chromosomes in gametesIn diploids, x = nFor 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*Creation and use of monoploid plantsCreation of monoploid plants (see Fig. 13.34a):Special treatment of germ cells from diploid speciesRare spontaneous events in large, natural populationsUsually 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 homozygosityIntroduce mutations into individual monoploid cellsSelect 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*The creation and use of monoploid plantsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.34Colchicine treatment prevents spindle formation and results in doubling of chromosome numbersCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.34cFormation of a triploid organismDiploid 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*Fig. 13.35aMeiosis in a triploid organismRegardless of how chromosomes pair, there is no way to ensure that gametes contain a complete balanced set of chromosomesAll polyploids with odd numbers of chromosome sets are sterile because they cannot produce balanced gametesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.35bGeneration of tetraploid (4x) cellsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Tetraploid cells occur during mitosis in a diploid when chromosomes fail to separate into two daughter cellsIf tetraploidy occurs in gamete precursors, diploid gametes are producedUnion of two diploid gametes produces a tetraploid organismAutopolyploid – all chromosome sets are derived from the same speciesFig. 13.36aIn a tetraploid, pairing of chromosomes as bivalents generates balanced gametesFour copies of each group of homologs pair two-by-two to form two bivalentsSuccessful tetraploids produce balanced 2X gametes and are fertileCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.36bGametes formed by A A a a tetraploidsTetraploids generate unusual Mendelian ratiosCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.36cPolyploids in agricultureOne-third of all known flowering plant species are polyploidPolyploidy often results in increased size and vigorMany polyploid plants have been selected for agricultural cultivationTetraploids – alfalfa, coffee, peanuts, Macintosh apples, Bartlett pearOctaploids – strawberries (Fig. 13.37)Allopolyploid – hybrids in which chromosome sets come from distinct, but related, speciesAmphidiploid – has two diploid parental speciese.g. Raphanobrassica – sterile F1 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*Creation of the allopolyploid TriticaleF1 hybrid of wheat and rye is sterile because there are no pairing partners for the rye chromosomesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.38aFertile Triticale can be created from infertile F1 hybrid Triticale Different Triticale hybrids have been generatedSome combine high yield of wheat with ability of rye to grow in unfavorable enviromentsSome combine high level of protein from wheat with high level of lysine from ryeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 13*Fig. 13.38a(cont)Emergent technologies: Beyond the karyotypeTwo main problems with traditional karyotypingProcedure is tedious and microscopic analysis is subjectiveVery low resolution – cannot detect deletions or duplications of < 5 MbDevelopment of microarray-based technologiesCan scan entire genome for chromosomal rearrangements and aneuploidyHas much higher accuracy, resolution, and throughputComparative 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*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*Fig. 13.39Detection of duplications and deletions by CGHAfter 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*(c) Incubate microarray with combined samplesFig. 13.39Aneuploidy in the human populationIncidence of abnormal phenotypes caused by aberrant chromosome organization or number is 0.004%Half of spontaneously aborted fetuses have chromosome abnormalitiesIncidence 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*Table 13.2