Genome-Wide Linkage Scan of Nonsyndromic Orofacial Clefting in 91 Families of Central European Origin
Genome-Wide Linkage Scan of Nonsyndromic Orofacial Clefting in 91 Families of Central European Origin
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DOI：
10.1002/ajmg.a.33136
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发表时间：
2009-12-01
影响因子：
2
通讯作者：
Lacava, Amalia Diaz
中科院分区：
文献类型：
--
作者：
Mangold, Elisabeth;Reutter, Heiko;Lacava, Amalia Diaz
口面部裂是所有先天性疾病中最常见的一种。伴有或不伴有腭裂 (NSCL/P) 和单纯腭裂 (NSCPO) 的非综合征性唇裂病例被认为具有多因素病因，涉及遗传和环境因素。我们展示了 91 个患有非综合征性口面部裂 (NSC) 的中欧血统家庭的全基因组连锁扫描结果。样本包括 74 个 NSCL/P 家庭、15 个 NSCPO 家庭和 2 个混合家庭（总共对 217 名受影响个体和 230 名未受影响个体进行了基因分型）。我们对 542 个微卫星标记进行了基因分型（平均标记间距离 = 6.9 cM）。使用 Allegro 2.0f 进行多点非参数连锁分析。除了之前全基因组连锁分析中研究的因素外，我们还搜索了性别特异性易感性位点、显示亲本印记的位点以及 NSCL/P 和 NSCPO 共享的位点。在名义显着性水平上鉴定了可能包含 NSC 易感位点的几个基因组区域。其中一些与之前研究中确定的区域重叠。基因座 4q21-q26 和 1p31-p21 获得了提示性连锁证据，其中 1 号染色体基因座显示出男性特异性遗传效应。我们的研究已经确定了用于鉴定 NSC 相关基因的有希望的染色体区域，并证明了进行详细统计分析的重要性，其中考虑了复杂的遗传机制，例如性别特异性效应和基因组印记。有必要对大量患者样本进行进一步研究，以确定 NSCL/P 和 NSCPO 的共同因素。 (C) 2009 Wiley-Liss, Inc.
Orofacial clefts are among the most common of all congenital disorders. Nonsyndromic cases of cleft lip with or without cleft palate (NSCL/P) and cleft palate only (NSCPO) are considered to have a multifactorial etiology which involves both genetic and environmental factors. We present the results of a genome-wide linkage scan in 91 families of central European descent with nonsyndromic orofacial clefts (NSC). The sample included 74 NSCL/P families, 15 NSCPO families, and 2 mixed families (a total of 217 affected and 230 unaffected individuals were genotyped). We genotyped 542 microsatellite markers (average intermarker distance = 6.9 cM). Multipoint nonparametric linkage analysis was performed using Allegro 2.0f. In addition to the factors investigated in previous genome-wide linkage analyses, we searched for sex-specific susceptibility loci, loci demonstrating parental imprinting and loci that are shared by NSCL/P and NSCPO. Several genomic regions likely to contain susceptibility loci for NSC were identified at the level of nominal significance. Some of these overlap with regions identified in previous studies. Suggestive evidence of linkage was obtained for the loci 4q21-q26 and 1p31-p21, with the chromosome 1 locus showing a male-specific genetic effect. Our study has identified promising chromosomal regions for the identification of NSC-associated genes, and demonstrates the importance of performing detailed statistical analyses which take into account complex genetic mechanisms such as sex-specific effects and genomic imprinting. Further research in large patient samples is necessary to identify factors common to NSCL/P and NSCPO. (C) 2009 Wiley-Liss, Inc.