Comparison of X-chromosome inactivation patterns in multiple tissues from human females
Comparison of X-chromosome inactivation patterns in multiple tissues from human females
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DOI：
10.1136/jmg.2007.055244
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发表时间：
2008-05-01
影响因子：
4
通讯作者：
Butler, M. G.
中科院分区：
文献类型：
--
作者：
Bittel, D. C.;Theodoro, M. F.;Butler, M. G.
背景资料：X染色体失活（XCI）是一种机制，通过这种机制，具有两条X染色体的雌性哺乳动物和具有一条X染色体的雄性哺乳动物之间实现基因剂量均匀性，并且被认为是随机发生的。对于分子遗传学检测，通常研究可接近的组织（例如血液），但与不可接近的组织（例如大脑）的关系知之甚少。对于可访问的组织是信息的遗传分析，组织类型之间的遗传结果的高度一致性是required.Objective：为了确定在不同年龄（胎儿至82岁）的女性多个组织之间的关系：XCI模式进行了分析，使用多态性雄激素受体（AR）基因检测。使用代表三个胚胎生殖层的34个尸检组织，从26名无恶性肿瘤史的不同人类女性中分离DNA。结果：分析了26名女性中13名女性的280个组织样本中的33个，显示出倾斜的XCI值（>80：20%）。组织间的平均XCI值无显著差异，但在研究的血液和其他组织中观察到XCI变异性随年龄增加的趋势（例如，0-2岁组研究的所有组织的SD为9.9%，而>60岁组为14.8%）。我们发现一个显着的相关性（r（s）= 0.51，p= 0.035）之间的XCI值的血液和/或脾脏和脑组织，并在大多数其他组织代表的三个胚胎germinlayers.Conclusions：在我们的研究中，XCI数据之间可访问（如血液）和不可访问的组织（如大脑）在不同年龄的女性，并可能是有用的基因检测。随着年龄的增长，XCI变异性有增加的趋势，特别是在老年女性（> 60岁）中。
Background: X-chromosome inactivation (XCI) is the mechanism by which gene dosage uniformity is achieved between female mammals with two X chromosomes and male mammals with a single X chromosome, and is thought to occur randomly. For molecular genetic testing, accessible tissues (eg blood) are commonly studied, but the relationship with inaccessible tissues (eg brain) is poorly understood. For accessible tissues to be informative for genetic analysis, a high degree of concordance of genetic findings among tissue types is required.Objective: To determine the relationship among multiple tissues within females at different ages (fetus to 82 years).Methods: XCI patterns were analysed using the polymorphic androgen receptor (AR) gene assay. DNA was isolated from 26 different human females without history of malignancy, using 34 autopsy tissues representing the three embryonic germ layers.Results: 33 of the 280 tissue samples analysed from 13 of the 26 females showed skewed XCI values (>80:20%). Average XCI value was not significantly different among the tissues, but a trend for increasing XCI variability was observed with age in blood and other tissues studied (eg the SD for all tissues studied for the 0-2 years group was 9.9% compared with 14.8% in the >60 years group). We found a significant correlation (r(s)= 0.51, p= 0.035) between XCI values for blood and/or spleen and brain tissue, and in most other tissues representing the three embryonic germ layers.Conclusions: In our study, XCI data were comparable among accessible (eg blood) and inaccessible tissues (eg brain) in females at various ages, and may be useful for genetic testing. A trend was seen for greater XCI variability with increasing age, particularly in older women (> 60 years).