Age-associated skewing of X-inactivation ratios of blood cells in normal females: a candidate-gene analysis approach
Age-associated skewing of X-inactivation ratios of blood cells in normal females: a candidate-gene analysis approach
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DOI：
10.1016/j.exphem.2005.06.023
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发表时间：
2005-10-01
影响因子：
2.6
通讯作者：
Busque, L
中科院分区：
文献类型：
--
作者：
Chagnon, P;Provost, S;Busque, L
X-失活是一个随机过程，发生在胚胎发育早期的女性。女性是嵌合体，具有相同比例的细胞，其中父方X染色体（Xp）或母方X染色体（Xm）处于活跃状态。然而，接近40%的健康女性年龄超过60岁。X-失活比率呈现显著的偏斜（Xp：Xm > 3：1）。血细胞中这种与年龄相关的偏斜（AAS）的确切病因尚不清楚。我们假设AAS是由于造血或细胞存活基因的等位基因变异引起的半合子细胞选择。为了验证这一假设，我们招募了700名年龄超过60岁的法裔加拿大健康女性。我们确定了在HUMARA基因座的X-失活率。我们使用TaqMan技术对15个不同的候选基因中的81个不同的SNPs进行了基因分型，这些候选基因在造血、细胞周期或X-失活中具有已知的作用。进行了广泛的统计分析，并表明，没有15个候选基因的研究有助于AAS显着。(c)2005年国际实验血液学学会。爱思唯尔公司出版
X-inactivation is a random process that occurs in females early during embryogenesis. Females are mosaics with an equal proportion of cells with the paternal (Xp) or maternal X-chromosome (Xm) in the active state. However, close to 40% of healthy females aged more than 60 y.o. present a significant skewing of X-inactivation ratios (Xp:Xm > 3 :1). The exact etiology of this age-associated skewing (AAS) in blood cells is unknown. We hypothesized that AAS is due to hemizygous cell selection caused by allelic variants in hematopoiesis or cell survival genes. To test this hypothesis, we recruited 700 unrelated healthy females of French Canadian ancestry aged more than 60. We determined X-inactivation ratio at the HUMARA locus. We genotyped 81 different SNPs, using TaqMan (R) technology, in 15 different candidate genes with known role in hematopoiesis, cell cycle, or X-inactivation. Extensive statistical analyses were conducted and demonstrated that none of the 15 candidate genes investigated contribute significantly to AAS. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc.