Autosomal dominant nonsyndromic cleft lip and palate: Significant evidence of linkage at 18q21.1
Autosomal dominant nonsyndromic cleft lip and palate: Significant evidence of linkage at 18q21.1
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DOI：
10.1086/518944
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发表时间：
2007-07-01
影响因子：
9.8
通讯作者：
Radhakrishna, Uppala
中科院分区：
文献类型：
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作者：
Beiraghi, Soraya;Nath, Swapan K.;Radhakrishna, Uppala
非综合征性唇裂伴或不伴腭裂（NSCL/ P）是最常见的先天性面部缺陷之一，在欧洲血统的个体中，发病率为700- 1000活产婴儿中有1例。一些nsl / P的连锁和关联研究已经提出了许多候选基因和基因组区域。使用单核苷酸多态性阵列对一个大型多代家族（UR410）进行了NSCL/ P全基因组连锁分析。非参数连锁（NPL）分析显示，18q21.1染色体上rs728683标记存在显著连锁（NPL = 43.33 P= 0.0061 LOD = 3.97 P= 0.00001）。参数连锁分析结果显示，在18q21.1染色体47.4 Mb位置，显性遗传模式和低外显率的LOD评分最高，为3.61。单倍型分析确定了一个5.7 Mb的基因组区域，近端标记rs1824683 （42,403,918 bp）和远端标记rs768206 （48,132,862 bp）。因此，在18q21.1上发现了一个新的基因组区域，最有可能在该家族中携带nsl / P的高风险变体；我们建议将此位点命名为“OFC11”（orofacial cleft 11）。
Nonsyndromic cleft lip with or without cleft palate (NSCL/ P) is one of the most common congenital facial defects, with an incidence of 1 in 700-1,000 live births among individuals of European descent. Several linkage and association studies of NSCL/ P have suggested numerous candidate genes and genomic regions. A genomewide linkage analysis of a large multigenerational family (UR410) with NSCL/ P was performed using a single-nucleotide-polymorphism array. Nonparametric linkage (NPL) analysis provided significant evidence of linkage for marker rs728683 on chromosome 18q21.1 (NPL = 43.33 P = .000061 LOD = 3.97 P= .00001). Parametric linkage analysis with a dominant mode of inheritance and reduced penetrance resulted in a maximum LOD score of 3.61 at position 47.4 Mb on chromosome 18q21.1. Haplotype analysis with informative crossovers defined a 5.7- Mb genomic region spanned by proximal marker rs1824683 (42,403,918 bp) and distal marker rs768206 (48,132,862 bp). Thus, a novel genomic region on 18q21.1 was identified that most likely harbors a high- risk variant for NSCL/ P in this family; we propose to name this locus "OFC11" (orofacial cleft 11).