1Changes in chromosome numberReading: Hartwell pp516-525Problem set at endChanges in whole sets of chromosomes-changes in ploidyChanges in # of individual chromosomes-aneuploidySome definitionsPloidy is the # of sets of chromosomesx is the number of chromosomes in a set.Haploid # (n) is the number of chromosomes in a gamete.For diploids, x = nBut in polyploids,where the ploidy is > 2x, n > xe.g., wheat is a hexaploid or 6x, where x = 7 and n = 21MonoploidsMale bees and wasps are naturally occuring monoploids,which develop by parthenogenesis.Can also generate experimentally.e.g., zebrafish, many plants.Zebrafish geneticists take advantage of monoploids ingenetic screens.Need to be studying a phenotype that you cansee during embryogenesis before monoploidsdie.In plants, can generate monoploids by culturingmeiotic products.2BUT sterile. In meiosis no pairing homologs.Only 2 gametes OKAll gametesabnormalWith increasing x, # of functional gametes decreasesTetraploids (4x), hexaploids (6x),octaploids (8x), ….Increasing ploidy increasing size2n 8nCan artificially use colchicine to increase ploidy.Triploids are sterile.Bananas, seedless watermelons are seedless becausethey are triploidGenerated by crossing diploid and tetraploid2x x 4x3x3But why are they sterile?2 gametes2x-OK2 gametes1x-OK2 gametesunbalanced2 gametesunbalancedUp until now we have been dealing withautopolyploids, which contain multiple sets ofchromosomes from the same species. Allopolyploids are produced from sets ofchromosomes of closely related species.Closely related chromosomes from different speciesare not homolgous, but are referred to ashomeologous.Homeologous chromosomes do not pair duringmeiosis and this can lead to problems.If cross two related species, ok until meiosis.Homeologouschromosomes don’t pair,which leads to sterility.But by doubling thechromosomes, generate anallopolyploid (amphidiploid)that is fertileTriticum (wheat)6n =42Gametes: 3n = 21Gametes: 3n = 21Secale (Rye)2n =14gametes: n = 7gametes: n = 7Sterile hybrid4n = 28One successful allopolyploid is TriticaleTriticale Triticale combines the high proteincombines the high proteincontent of wheat with the high lysinecontent of wheat with the high lysinelevels and ability to adapt to marginallevels and ability to adapt to marginalenvironments of rye.environments of rye.Fertile ‘Triticale’8n =56Chromosomedoubling withcolchicine.AneuploidyAmniocentesis4Chromosomes can be identified by their sizeand banding pattern...Normal female, XXNormal male, XYMeiosis results in gametes with a single set of chromosomes!Nondisjunction in meiosis I or II results in gameteswith an extra or missing chromosome.When these gametes fuse, the fusion results inzygotes with an extra or missing chromosome, asituation termed aneuploidy!What are the consequences of aneuploidy inhumans?5All monosomic (43 autosomes; missing an autosome)spontaneously abort (miscarriage).Almost all trisomic (45 autosomes; an extra autosome)fetuses spontaneously abort!There are exceptions.Autosomes first!Trisomy 13; Patau Syndrome Trisomy 18; Edwards SyndromeMany fetuses spontaneously abortThose that make it die in first yearTrisomy 21; Down SyndromeCan survive to age 50Mental retardationBut, why do aneuploid fetuses die?1000s of genes are over or under expressed!Resulting in genetic imbalance.(the consequences of genetic imbalance are differentin plants and animals.)6But the rules are different for the sex chromosomes!Turner syndrome, XOFemaleShort, wide-chestedUnderdeveloped breastsRudimentary ovariesSterileNormal intelligenceALL autosomal monosomics die,BUT XO individuals often survive andcan be relatively normal!!!There is something different about theautosomes and sex chromosomes.Klinefelter syndrome, XXYMalePhenotype of syndromenot apparent until pubertyBreast developmentLow fertilitySubnormal intelligenceThe Y chromosome is necessary and sufficient formale development!But what on Y is important for maledevelopment?SRY is both necessary and sufficientfor male developmentThe mouse on the left is XYand the mouse on the right isXX and has an SRY transgene--both are phenotypic males7Yet another difference between sexchromosomes and autosomes.Autosomal trisomies die, but XXY,XYY and XXX trisomies survive.BUT WHY?One of the first clues came from Liane RussellMice heterozygous for a recessive coat color mutation (c)on an autosome had wild-type (dark) fur. (homozygotes havewhite fur)c+c+X chromosomes autosomeBut a strain carrying a reciprocal translocation (more onthese later) between X and the autosome was variegated,having patches of wild-type and mutant fur.In other words, having thewild-type coat color genefused to X resulted in amutant phenotype in sometissues.Additional resultsX-linked mutations sometimes result in variegatedphenotype in females.Females that are heterozygous for a mutant versionof the glucose-6-phosphate dehydrogenase gene thatlacks activity and produces an electrophoretic variantwere analyzed. When tissue from these individualswas analyzed, it possessed activity and containedboth isoforms. If isolated cells were cultured andthen examined, the clones either had G-6-PD activityor lacked it, expressing only a single isoform.Murray Barr noted that the nuclei of female but notmale cats contained a darkly stained element. This isnow known as a Barr body.XXOne Barr bodyXXXTwo Barr bodies8Karyotype # Barr bodiesXY 0XO 0XX 1XXX 2In 1961 Mary Lyon proposed that in mammals, the dose ofgene products was equalized between males and females byinactivating one of the X chromosomes in females. Theinactive X is the Barr body. This mechanism of dosagecompensation is often referred to as the Lyon hypothesis.In mammalian females, early in embryonicdevelopment each cell inactivates one XchromosomeWhoa!!! All mammalian females are mosaic!!!These cells express onlypaternal X chromosome genes.These cells express onlymaternal X chromosomegenes.Female Calico cats have black and orange alleles ofan X-linked gene.X inactivation results in black andorange patches on Calico cats.These cells express onlypaternal black gene.These cells express onlymaternal orange gene.orange geneblack gene9Certain X-linked inherited traits result inmosaicism in females.e.g., anhidrotic ectodermal dysplasiaBut how is only one X inactivated?Studies of X:autosome translocations defined a specificsite on X, known as the X-inactivation center (Xic), thatwas required for inactivation.X
View Full Document
Unlocking...