Genomic Responses to Abnormal Gene Dosage The X Chromosome Improved on a Common Strategy 英文参考文献.docVIP

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Genomic Responses to Abnormal Gene Dosage The X Chromosome Improved on a Common Strategy 英文参考文献.doc

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Genomic Responses to Abnormal Gene Dosage The X Chromosome Improved on a Common Strategy 英文参考文献

Primer 1 GenomicResponsestoAbnormalGeneDosage:TheX ChromosomeImprovedonaCommonStrategy XinxianDeng1,ChristineM.Disteche1,2* 1Department of Pathology, University of Washington, Seattle, Washington, United States of America, 2Department of Medicine, University of Washington, Seattle, Washington,UnitedStatesofAmerica Mechanismstoguardgenomicintegrityarecriticaltoensuring the welfare and survival of an organism. Disruptions of genomic integritycanresultinaneuploidy,alarge-scalegenomicimbalance caused by either extra or missing whole chromosomes (chromo- somalaneuploidy)orchromosomesegments(segmentalaneuploi- dy).Achangeindosageofasinglegenemaynotcompromisethe well-being of an organism, but the combined altered dosage of manygenesduetoaneuploidydisturbstheoverallbalanceofgene expression networks, resulting in decreased fitness and mortality [1,2]. Chromosomal aneuploidy is a common cause of birth defects—Down syndrome is caused by an extra copy of Chromosome 21, and Turner syndrome by a single copy of the X chromosome in females. Furthermore, methods that detect segmentalaneuploidyhaveuncoveredsmalldeletionsorduplica- tions of the genome in association with many disorders, such as mentalretardation.Chromosomalandsegmentalaneuploidiesare also frequent in cancer cells in which changes in copy number paradoxicallyincreasecellfitnessbutareunfavorabletosurvivalof theorganism.Afundamentalissueinbiologyandmedicineisto understand the effects of aneuploidy on gene expression and the mechanisms that alleviate aneuploidy-induced imbalance of the genome. increaseingenedosagefrom2to3,duetoachromosomalgainor duplication,wouldproduce1.5-foldmoreproducts(Figure1).In the second scenario, the amount of products from altered gene dosagewouldeitherequalornearlyequalthatinWTcells,dueto completeorpartialcompensation(Figure1). Geneexpressionanalysesofaneuploidcellsortissuesinhuman, mouse, fly, yeast, and plant provide examples of both primary dosage effects and dosage compensation. Hence, c