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猪母性行为杀婴的关联与单体型分析:人类产褥期精神病的模型?

An association and haplotype analysis of porcine maternal infanticide: a model for human puerperal psychosis?

机构信息

Human Molecular Genetics Group, Department of Pathology, University of Cambridge, Cambridge, UK.

出版信息

Am J Med Genet B Neuropsychiatr Genet. 2012 Dec;159B(8):908-27. doi: 10.1002/ajmg.b.32097. Epub 2012 Sep 13.

Abstract

An association analysis using the Illumina porcine SNP60 beadchip was performed to identify SNPs significantly associated with porcine maternal infanticide. We previously hypothesised that this was a good animal model for human puerperal psychosis, an extreme form of postnatal mood disorder. Animals were selected from carefully phenotyped unrelated infanticide and control groups (representing extremes of the phenotypic spectrum), from four different lines. Permutation and sliding window analyses and an analysis to see which haplotypes were in linkage disequilibrium (LD) were compared to identify concordant regions. Across all analyses, intervals on SSCs 1, 3, 4, 10, and 13 were constant, contained genes associated with psychiatric or neurological disorders and were significant in multiple lines. The strongest (near GWS) consistent candidate region across all analyses and all breeds was the one located on SSC3 with one peak at 23.4 Mb, syntenic to a candidate region for bipolar disorder and another at 31.9 Mb, syntenic to a candidate region for human puerperal psychosis (16p13). From the haplotype/LD analysis, two regions reached genome wide significance (GWS): the first on SSC4 (KHDRBS3 to FAM135B), which was significant (-logP 5.57) in one Duroc based breed and is syntenic to a region in humans associated with cognition and neurotism; the second on SSC15, which was significant (-log10P 5.68) in two breeds and contained PAX3, which is expressed in the brain.

摘要

利用 Illumina 猪 SNP60 珠芯进行关联分析,以鉴定与猪母代杀婴行为显著相关的 SNP。我们之前假设这是人类产后精神病的良好动物模型,产后精神病是一种极端的产后情绪障碍。从四个不同的系中选择来自精心表型无关的杀婴和对照组(代表表型谱的极端)的动物。通过置换和滑动窗口分析以及分析哪些单倍型处于连锁不平衡(LD)来比较识别一致的区域。在所有分析中,SSC1、3、4、10 和 13 上的区间是恒定的,包含与精神或神经障碍相关的基因,并且在多个系中具有重要意义。在所有分析和所有品种中,最强(接近 GWS)的一致候选区域是位于 SSC3 上的一个区域,在 23.4 Mb 处有一个峰值,与双相情感障碍的候选区域和另一个位于 31.9 Mb 处的候选区域连锁,与人类产后精神病(16p13)的候选区域连锁。从单倍型/ LD 分析中,有两个区域达到全基因组显著性(GWS):第一个位于 SSC4(KHDRBS3 到 FAM135B),在一个杜洛克基础品种中显著(-logP 5.57),与人类认知和神经质相关区域连锁;第二个位于 SSC15,在两个品种中显著(-log10P 5.68),包含在大脑中表达的 PAX3。

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