genomic responses to abnormal gene dosage the x chromosome improved on a common strategy基因组反应异常基因剂量x染色体在一个常见的改善策略.pdfVIP

Primer 1 Genomic Responses to Abnormal Gene Dosage: The X Chromosome Improved on a Common Strategy 1 1,2 Xinxian Deng , Christine M. Disteche * 1 Department of Pathology, University of Washington, Seattle, Washington, United States of America, 2 Department of Medicine, University of Washington, Seattle, Washington, United States of America Mechanisms to guard genomic integrity are critical to ensuring increase in gene dosage from 2 to 3, due to a chromosomal gain or the welfare and survival of an organism. Disruptions of genomic duplication, would produce 1.5-fold more products (Figure 1). In integrity can result in aneuploidy, a large-scale genomic imbalance the second scenario, the amount of products from altered gene caused by either extra or missing whole chromosomes (chromo- dosage would either equal or nearly equal that in WT cells, due to somal aneuploidy) or chromosome segments (segmental aneuploi- complete or partial compensation (Figure 1). dy). A change in dosage of a single gene may not compromise the Gene expression analyses of aneuploid cells or tissues in human, well-being of an organism, but the combined altered dosage of mouse, fly, yeast, and plant provide examples of both primary many genes due to aneuploidy disturbs the overall balance of gene dosage effects and dosage compensation. Hence, changes in expression networks, resulting in decreased fitness and mortality expression levels due to chromosomal aneuploidy do not affect all [1,2]. Chromosomal aneuploidy is a common cause of birth genes in the same manner. For example, in Down syndrome, 29% defects—Down syndrome is