Recent genetics of Cleft Lip and Palate

唇裂和腭裂的最新遗传学

• 批准号: 20791560
• 负责人: SUZUKI Satoshi
• 金额: $ 2.5万
• 依托单位: Aichi Gakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20791560/
• 关键词: 口唇裂; 口蓋裂; 口唇口蓋裂; TGFB遺伝子; BMP4遺伝子

Nonsyndromic cleft lip with or without cleft palate (CL/P), a common birth defect, is a complex trait, arising from the influence of genetic and environmental factors. There are many studies have been reported. Our study supports the role of BMP4 in nonsyndromic CL/P, with mutations in BMP4 associated with microforms and OO, and polymorphic variants increasing the susceptibility to overt CL/P.A recent study of variants in the IRF6 gene showed variants in an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. We have also previously reported the linkage of NS CL/P to the 6p23 region that contains TFAP2A gene. We genotyped 8 SNPs in and near TFAP2A and FBAT was used for transmission disequilibrium test. A statistically significant association between CL/P and TFAP2A (p<0.001) was shown for rs1675414. These results support a direct role for variation of TFAP2A in orofacial clefting and suggests that examination of additional members of this pathway and deeper investigation of SNPs at the TFAP2A locus may disclose etiologic variants. Also recent Genome wide associations study discovered multiple loci such as MAFB, VAX1 and PAX7. We genotyped single nucleotide polymorphisms (SNPs) in or near VAX1, MAFB and PAX7. Results showed strong association between these genes and cleft lip and palate.

非综合征性唇腭裂（CL/P）是一种常见的出生缺陷，是遗传和环境因素共同作用的结果。有许多研究已经报道。我们的研究支持BMP 4在非综合征型CL/P中的作用，BMP 4的突变与微小型和OO相关，多态性变异增加了对明显CL/P的易感性。最近对IRF 6基因变异的研究表明，IRF 6增强子中AP-2 α结合位点的变异与唇裂相关。我们以前也报道了NS CL/P与含有TFAP 2A基因的6p 23区域的连锁。我们对TFAP 2A及其附近的8个SNPs进行了基因分型，并使用FBAT进行了传递不平衡检验。对于rs 1675414，CL/P和TFAP 2A之间的统计学显著关联（p<0.001）被显示。这些结果支持TFAP 2A变异在口面裂中的直接作用，并表明对该途径的其他成员进行检查和对TFAP 2A位点的SNP进行更深入的调查可能会揭示病因变异。最近的全基因组关联研究也发现了多个基因座，如MAFB，VAX 1和PAX 7。我们对VAX 1、MAFB和PAX 7中或附近的单核苷酸多态性（SNP）进行了基因分型。结果显示这些基因与唇腭裂有很强的相关性。

项目成果

TFAP2A is associated with nonsyndromic Cleft Lip and Palate

TFAP2A 与非综合征性唇裂和腭裂相关

• 发表时间: 2009
• 作者: Suzuki S;Marazita ML;Cooper ME;Miwa N;Hing A;Jugessur A;Natsume N;Shimozato K;Ohbayashi N;Suzuki Y;Niimi T;Minami K;Yamamoto M;Altannamar TJ;Erkhembaatar T;Furukawa H;Daack-Hirsch S;L' heureux J;Brandon CA;Weinberg SM;Nei swanger K;De;鈴木聡;Satoshi Suzuki;鈴木聡;Satoshi Suzuki
• 通讯作者: Satoshi Suzuki

Replication of genome wide association findings for Cleft Lip and Palate a role for variants in MAFB, VAX1 and PAX7 in Asian population

唇腭裂全基因组关联研究结果的复制对亚洲人群中 MAFB、VAX1 和 PAX7 变异的作用

• 发表时间: 2010
• 作者: Suzuki S;Marazita ML;Cooper ME;Miwa N;Hing A;Jugessur A;Natsume N;Shimozato K;Ohbayashi N;Suzuki Y;Niimi T;Minami K;Yamamoto M;Altannamar TJ;Erkhembaatar T;Furukawa H;Daack-Hirsch S;L' heureux J;Brandon CA;Weinberg SM;Nei swanger K;De;鈴木聡;Satoshi Suzuki
• 通讯作者: Satoshi Suzuki

Mutations in BMP4 Are Associated with Subepithelial, Microform, and Overt Cleft Lip

• DOI: 10.1016/j.ajhg.2009.02.002
• 发表时间: 2009-03-13
• 期刊: AMERICAN JOURNAL OF HUMAN GENETICS
• 影响因子: 9.8
• 作者: Suzuki, Satoshi;Marazita, Mary L.;Murray, Jeffrey C.
• 通讯作者: Murray, Jeffrey C.

Replication of genome wide association findings for Cleft Lip and Palste a role for variants in MAFB, VAX1 and PAX7 in Asian population

唇裂和 Palste 基因组范围关联研究结果的复制对亚洲人群中 MAFB、VAX1 和 PAX7 变异的作用

• 发表时间: 2010
• 作者: Suzuki S;Marazita ML;Cooper ME;Miwa N;Hing A;Jugessur A;Natsume N;Shimozato K;Ohbayashi N;Suzuki Y;Niimi T;Minami K;Yamamoto M;Altannamar TJ;Erkhembaatar T;Furukawa H;Daack-Hirsch S;L' heureux J;Brandon CA;Weinberg SM;Nei swanger K;De;鈴木聡;Satoshi Suzuki;鈴木聡
• 通讯作者: 鈴木聡