Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results.
Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results.
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DOI：
10.1159/000224636
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发表时间：
2009
期刊：
影响因子：
1.8
通讯作者：
Arcos-Burgos M
中科院分区：
文献类型：
--
作者：
Marazita ML;Lidral AC;Murray JC;Field LL;Maher BS;Goldstein McHenry T;Cooper ME;Govil M;Daack-Hirsch S;Riley B;Jugessur A;Felix T;Morene L;Mansilla MA;Vieira AR;Doheny K;Pugh E;Valencia-Ramirez C;Arcos-Burgos M
非综合征性唇腭裂，即唇裂（CL）和腭裂（CP），是最常见的出生缺陷之一。本研究的目的是确定有或无CP（CL/P）的CL基因组区域和基因。我们在820个多重CL/P家族（6，565个个体）中进行了10 cM基因组扫描的连锁分析。显著连锁结果之后是候选基因和区域中的1，476个SNP的关联分析，利用加权错误发现率（wFDR）方法来控制多次测试并结合基因组扫描结果。在1 q32、2 p13、3q 27 -28、9 q21、12 p11、14 q21 -24和16 q24区域发现了显著（多点HLOD≥3.2）或全基因组显著（HLOD≥4.02）连锁结果。IRF 6（1 q32）和FOXE 1（9 q21）中或附近的SNP达到了正式的全基因组wFDR调整的显著性。此外，结果是表型依赖性的，因为IRF 6区域结果对于受影响个体仅具有CL的家族最显著，并且FOXE 1区域结果对于部分或全部受影响个体具有CL伴CP的家族最显著。这些结果强调了在大样本家庭中仔细描绘表型对于复杂异质性状（如CL/P）的遗传分析的重要性。
Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects. The goal of this study was to identify genomic regions and genes for CL with or without CP (CL/P). We performed linkage analyses of a 10 cM genome scan in 820 multiplex CL/P families (6,565 individuals). Significant linkage results were followed by association analyses of 1,476 SNPs in candidate genes and regions, utilizing a weighted false discovery rate (wFDR) approach to control for multiple testing and incorporate the genome scan results. Significant (multipoint HLOD≥3.2) or genome-wide-significant (HLOD≥4.02) linkage results were found for regions 1q32, 2p13, 3q27-28, 9q21, 12p11, 14q21-24 and 16q24. SNPs in IRF6 (1q32) and in or near FOXE1 (9q21) reached formal genome-wide wFDR-adjusted significance. Further, results were phenotype dependent in that the IRF6 region results were most significant for families in which affected individuals have CL alone, and the FOXE1 region results were most significant in families in which some or all of the affected individuals have CL with CP. These results highlight the importance of careful phenotypic delineation in large samples of families for genetic analyses of complex, heterogeneous traits such as CL/P.
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影响因子：
3.5
作者：
Castanet, M;Park, SM;Polak, M
通讯作者：
Polak, M
影响因子：
3.5
作者：
Chiquet, Brett T.;Lidral, Andrew C.;Hecht, Jacqueline T.
通讯作者：
Hecht, Jacqueline T.
DOI：
10.1101/sqb.2003.68.69
发表时间：
2003-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Fan, JB;Oliphant, A;Chee, MS
通讯作者：
Chee, MS
影响因子：
3.5
作者：
Cai, JL;Ash, D;Lovett, M
通讯作者：
Lovett, M
影响因子：
2
作者：
Gläser, B;Rossier, E;Kehrer-Sawatzki, H
通讯作者：
Kehrer-Sawatzki, H