Resolving ATM haplotypes in whites.
Resolving ATM haplotypes in whites.
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解析白人的 ATM 单倍型。
DOI：
10.1086/373879
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发表时间：
2003
影响因子：
9.8
通讯作者：
Nathanson,KatherineL
中科院分区：
文献类型：
--
作者：
Letrero,Richard;Weber,BarbaraL;Nathanson,KatherineL
在最近的两项研究中，Bonnen 等人。和托尔斯滕森等人。使用 SNP 证明了沿 ATM（GenBank 登录号 U82828）分布的广泛连锁不平衡（Bonnen 等人，2000 年；Thorstenson 等人，2001 年）。在白人（欧洲人）中，沿 ATM 未观察到重组。然而，两篇文章之间存在一些差异，因为 Thorstenson 等人。在白人中发现了三种单倍型（H2、H3 和 H4），而 Bonnen 等人。在白人中发现了频率为 15% 的五种主要单倍型（2、3、15、17 和 22）和两种次要单倍型。托尔斯滕森等人。表明单倍型 2 和 H4 可能是等效的，17 和 H2 以及 15 和 H3 也可能是等效的。然而，单倍型 22（由 Bonnen 等人确定占总体的 35%）并未在建议的等价性中得到考虑。这两项研究只有一个重叠的 SNP 用于确定单倍型，这可能导致了差异。因为我们对 ATM 与乳腺癌关联研究的单倍型感兴趣，所以我们比较了来自 83 个不相关家庭的 159 名具有有害 BRCA1 突变的个体的两项研究的单倍型，以确定哪些单倍型是等效的。来自 83 个家庭的先证者全部携带 BRCA1 突变，其中 72 个患有癌症，11 个未患癌症。此外，我们试图确定先前研究的三个非保守编码区 SNP（S49C、D1853N 和 P1054R）与每个单倍型的关联。正如 Thorstenson 等人所描述的，所有种群中共有 12 个非保守编码区 SNP，其中 4 个出现在白人中（S49C、F868L、D1853N 和 P1054R）。正如 Thorstenson 等人所言，我们对检查 SNP 与单倍型的关联特别感兴趣。发现 D1853N 定义了单个单倍型 (H3)，这与 Bonnen 等人独立描述单倍型 15（建议的 H3 等价物）不同。
In two recent studies, Bonnen et al. and Thorstenson et al. demonstrated extensive linkage disequilibrium distributed along ATM (GenBank accession number U82828) using SNPs (Bonnen et al. 2000; Thorstenson et al. 2001). In whites (Europeans), no recombination was observed along ATM. However, there are some discrepancies between the two articles, in that Thorstenson et al. found three haplotypes (H2, H3, and H4) in whites, whereas Bonnen et al. found five major haplotypes with frequencies 15%(2, 3, 15, 17, and 22) and two minor haplotypes in whites. Thorstenson et al. suggest that haplotype 2 and H4 may be equivalent, as may be 17 and H2 and 15 and H3. However, haplotype 22, which accounts for 35% of the population as determined by Bonnen et al., was not accounted for in the suggested equivalency. The two studies had only one overlapping SNP used to determine haplotypes, which may contribute to the discrepancy. Because we are interested in haplotyping ATM for association studies with breast cancer, we compared the haplotypes from the two studies in 159 individuals from 83 unrelated families with deleterious BRCA1 mutations in order to determine which haplotypes are equivalent. Of the probands from the 83 families, all of whom carried BRCA1 mutations, 72 were affected with cancer and 11 were not affected with cancer. In addition, we sought to determine the association of the three previously studied nonconservative coding region SNPs (S49C, D1853N, and P1054R) with each haplotype. As delineated by Thorstenson et al., there is a total of 12 nonconservative coding region SNPs in all populations, of which four appear in whites (S49C, F868L, D1853N, and P1054R). We were particularly interested in examining the association of the SNPs with the haplotypes, as Thorstenson et al. found that D1853N defined a single haplotype (H3), unlike Bonnen et al., who describe haplotype 15 (the suggested equivalent of H3) independently.