CRISPLD2: a novel NSCLP candidate gene
CRISPLD2: a novel NSCLP candidate gene
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DOI：
10.1093/hmg/ddm176
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发表时间：
2007-09-15
影响因子：
3.5
通讯作者：
Hecht, Jacqueline T.
中科院分区：
文献类型：
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作者：
Chiquet, Brett T.;Lidral, Andrew C.;Hecht, Jacqueline T.
非综合征性唇裂伴或不伴腭裂(NSCLP)是基因与环境因素复杂相互作用的结果。候选基因分析和基因组扫描已经被用来识别与NSCLP有关的基因。在这项研究中，我们评估了16q24.1染色体区域，该区域已被多次基因组扫描确定为感兴趣的NSCLP区域。在该区域发现了两个候选基因：干扰素调节因子8(IRF8)和富含半胱氨酸的分泌蛋白LCCL结构域包含2(CRISPLD2)。最初，对高加索人和西班牙裔NSCLP多基因家庭和单亲亲子三人组进行了IRF8和CRISPLD2的单核苷酸多态(SNPs)基因分型。CRISPLD2随后在由来自南美洲哥伦比亚的NSCLP家庭组成的数据集中进行了基因分型。连锁不平衡分析发现CRISPLD2和NSCLP在我们的高加索人和西班牙裔NSCLP队列中都有显著的关联。SNP rs1546124和rs1546124与rs4783099或rs16974880之间的单倍型在高加索多基因群体中具有显著意义(分别为P=0.01、P=0.002和P=0.001)。在西班牙裔人群中检测到CRISPLD2 SNPs rs8061351(P=0.02)和rs2326398(P=0.06)的遗传变异。没有发现CRISPLD2与我们的哥伦比亚人口或IRF8和NSCLP之间的关联。原位杂交结果表明，CRISPLD2基因在E13.5~E17.5的颅面发育过程中分别在下颌、腭部和鼻咽部表达。综上所述，这些数据表明CRISPLD2基因变异在NSCLP的病因学中起作用。
Non-syndromic cleft lip with or without cleft palate (NSCLP) results from the complex interaction between genes and environmental factors. Candidate gene analysis and genome scans have been employed to identify the genes contributing to NSCLP. In this study, we evaluated the 16q24.1 chromosomal region, which has been identified by multiple genome scans as an NSCLP region of interest. Two candidate genes were found in the region: interferon regulatory factor 8 (IRF8) and cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2). Initially, Caucasian and Hispanic NSCLP multiplex families and simplex parent-child trios were genotyped for single nucleotide polymorphisms (SNPs) in both IRF8 and CRISPLD2. CRISPLD2 was subsequently genotyped in a data set comprised of NSCLP families from Colombia, South America. Linkage disequilibrium analysis identified a significant association between CRISPLD2 and NSCLP in both our Caucasian and Hispanic NSCLP cohorts. SNP rs1546124 and haplotypes between rs1546124 and either rs4783099 or rs16974880 were significant in the Caucasian multiplex population (P = 0.01, P = 0.002 and P = 0.001, respectively). An altered transmission of CRISPLD2 SNPs rs8061351 (P = 0.02) and rs2326398 (P = 0.06) was detected in the Hispanic population. No association was found between CRISPLD2 and our Colombian population or IRF8 and NSCLP. In situ hybridization showed that CRISPLD2 is expressed in the mandible, palate and nasopharynx regions during craniofacial development at E13.5-E17.5, respectively. Altogether, these data suggest that genetic variation in CRISPLD2 has a role in the etiology of NSCLP.