Brief research communication - Further evidence of a maternal parent-of-origin effect on chromosome 10 in late-onset Alzheimer's disease
Brief research communication - Further evidence of a maternal parent-of-origin effect on chromosome 10 in late-onset Alzheimer's disease
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DOI：
10.1002/ajmg.b.30350
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发表时间：
2006-07-05
影响因子：
2.8
通讯作者：
Fallin, M. Daniele
中科院分区：
文献类型：
--
作者：
Bassett, Susan Spear;Avramopoulos, Dimitrios;Fallin, M. Daniele
最近，染色体10q区域在晚发性阿尔茨海默病(LOAD)中受到了极大的关注，因为越来越多的证据表明，染色体10q区域与LOAD或A-β水平有关，几个小组报告了这一点。在最近的一篇论文中，我们报告了在我们的NIMH AD遗传学倡议家系子集中该区域连锁的证据，当只分析起源于母体疾病的家庭时，接近全基因组意义(非参数LOD分数=3.27)[Bassett等人。(2002)；Am J MedGenet 114：679-686]。我们现在扩展了这项工作，使用来自阿拉巴马大学伯明翰分校(UAB)的NIMH AD家系的独立子集，并使用父母起源信息显示了进一步的连锁证据。在我们的霍普金斯样本中，与未分层的样本相比，母系而不是父系的家系在染色体10q区域的连锁显著增加。结合我们之前对该区域的精细作图工作的数据和在所有家系中分型的五个新标记，在同一区域的非参数LOD值为3.73LOD值，该值达到了全基因组范围的连锁意义，经验P值=0.003。这些结果支持了我们早先的发现，缩小了感兴趣的区域。结合其他研究小组的发现，这些结果提供了进一步的证据，证明10号染色体区域包含一个与LOAD有关的基因，我们使用父母起源信息在进一步缩小感兴趣区域方面是有用的。(C)2006年Wiley-Liss，Inc.
The chromosome 10q region has recently received a great deal of attention in late-onset Alzheimer's disease (LOAD), given the growing evidence of linkage to LOAD, or to A-beta levels, reported by several groups. In a recent paper we reported evidence of linkage in this region in our subset of the NIMH AD genetics initiative pedigrees, approaching genome-wide significance (nonparametric LOD score = 3.27), when only families with maternal disease origin were analyzed [Bassett et al. (2002); Am J Med Genet 114:679-686]. We have now extended this work, using an independent subset of NIMH AD pedigrees from the University of Alabama at Birmingham (UAB), and show further evidence of linkage using parent-of-origin information. As in our Hopkins sample, maternal but not paternal pedigrees show significantly increased linkage in the chromosome 10q region compared to the unstratified sample. Combining data from our previous fine-mapping work on this region and five new markers genotyped in all pedigrees results in a non-parametric LOD score of 3.73 in the same region, a value that reaches genome wide significance for linkage, with an empirical P value = 0.003. These results support our earlier findings and narrow the region of interest. In combination with findings from other groups, these results provide further evidence that this chromosome 10 region harbors a gene implicated in LOAD, and our use of parent-of-origin information has been useful in further narrowing the region of interest. (c) 2006 Wiley-Liss, Inc.