Large-scale population study of human cell lines indicates that dosage compensation is virtually complete

被引:108
作者
Johnston, Colette M. [1 ]
Lovell, Frances L. [1 ]
Leongamornlert, Daniel A. [1 ]
Stranger, Barbara E. [2 ]
Dermitzakis, Emmanouil T. [2 ]
Ross, Mark T. [1 ]
机构
[1] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Chromosome Grp 10, Cambridge, England
[2] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Populat & Comparat Genom Grp, Cambridge, England
来源
PLOS GENETICS | 2008年 / 4卷 / 01期
基金
英国惠康基金;
关键词
D O I
10.1371/journal.pgen.0040009
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
X chromosome inactivation in female mammals results in dosage compensation of X-linked gene products between the sexes. In humans there is evidence that a substantial proportion of genes escape from silencing. We have carried out a large-scale analysis of gene expression in lymphoblastoid cell lines from four human populations to determine the extent to which escape from X chromosome inactivation disrupts dosage compensation. We conclude that dosage compensation is virtually complete. Overall expression from the X chromosome is only slightly higher in females and can largely be accounted for by elevated female expression of approximately 5% of X-linked genes. We suggest that the potential contribution of escape from X chromosome inactivation to phenotypic differences between the sexes is more limited than previously believed.
引用
收藏
页码:0088 / 0098
页数:11
相关论文
共 34 条
  • [1] A NOVEL X-GENE WITH A WIDELY TRANSCRIBED Y-LINKED HOMOLOG ESCAPES X-INACTIVATION IN MOUSE AND HUMAN
    AGULNIK, AI
    MITCHELL, MJ
    MATTEI, MG
    BORSANI, G
    AVNER, PA
    LERNER, JL
    BISHOP, CE
    [J]. HUMAN MOLECULAR GENETICS, 1994, 3 (06) : 879 - 884
  • [2] A haplotype map of the human genome
    Altshuler, D
    Brooks, LD
    Chakravarti, A
    Collins, FS
    Daly, MJ
    Donnelly, P
    Gibbs, RA
    Belmont, JW
    Boudreau, A
    Leal, SM
    Hardenbol, P
    Pasternak, S
    Wheeler, DA
    Willis, TD
    Yu, FL
    Yang, HM
    Zeng, CQ
    Gao, Y
    Hu, HR
    Hu, WT
    Li, CH
    Lin, W
    Liu, SQ
    Pan, H
    Tang, XL
    Wang, J
    Wang, W
    Yu, J
    Zhang, B
    Zhang, QR
    Zhao, HB
    Zhao, H
    Zhou, J
    Gabriel, SB
    Barry, R
    Blumenstiel, B
    Camargo, A
    Defelice, M
    Faggart, M
    Goyette, M
    Gupta, S
    Moore, J
    Nguyen, H
    Onofrio, RC
    Parkin, M
    Roy, J
    Stahl, E
    Winchester, E
    Ziaugra, L
    Shen, Y
    [J]. NATURE, 2005, 437 (7063) : 1299 - 1320
  • [3] DOSAGE COMPENSATION IN DROSOPHILA
    BAKER, BS
    GORMAN, M
    MARIN, I
    [J]. ANNUAL REVIEW OF GENETICS, 1994, 28 : 491 - 521
  • [4] Expression of genes from the human active and inactive X chromosomes
    Brown, CJ
    Carrel, L
    Willard, HF
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 60 (06) : 1333 - 1343
  • [5] X-inactivation profile reveals extensive variability in X-linked gene expression in females
    Carrel, L
    Willard, HF
    [J]. NATURE, 2005, 434 (7031) : 400 - 404
  • [6] X inactivation analysis and DNA methylation studies of the ubiquitin activating enzyme E1 and PCTAIRE-1 genes in human and mouse
    Carrel, L
    Clemson, CM
    Dunn, JM
    Miller, AP
    Hunt, PA
    Lawrence, JB
    Willard, HF
    [J]. HUMAN MOLECULAR GENETICS, 1996, 5 (03) : 391 - 401
  • [7] A first-generation X-inactivation profile of the human X chromosome
    Carrel, L
    Cottle, AA
    Goglin, KC
    Willard, HF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (25) : 14440 - 14444
  • [8] Silencing of the mammalian X chromosome
    Chow, JC
    Yen, Z
    Ziesche, SM
    Brown, CJ
    [J]. ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, 2005, 6 : 69 - 92
  • [9] Application of microarrays to the analysis of the inactivation status of human X-linked genes expressed in lymphocytes
    Craig, IW
    Mill, J
    Craig, GM
    Loat, C
    Schalkwyk, LC
    [J]. EUROPEAN JOURNAL OF HUMAN GENETICS, 2004, 12 (08) : 639 - 646
  • [10] DEMONSTRATION OF 2 POPULATIONS OF CELLS IN HUMAN FEMALE HETEROZYGOUS FOR GLUCOSE-6-PHOSPHATEDEHYDROGENASE VARIANTS
    DAVIDSON, RG
    NITOWSKY, HM
    CHILDS, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1963, 50 (03) : 481 - &