Riley B M, Schultz R E, Cooper M E, Goldstein-McHenry T, Daack-Hirsch S, Lee K T, Dragan E, Vieira A R, Lidral A C, Marazita M L, Murray J C
Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA.
Am J Med Genet A. 2007 Apr 15;143A(8):846-52. doi: 10.1002/ajmg.a.31673.
Isolated or nonsyndromic cleft lip and palate (NS CLP) is a complex disorder resulting from multiple genetic and environmental factors. NS CLP has a birth prevalence of 1 per 500 in the Philippines where large families provide an opportunity for gene localization. Genotyping of 392 microsatellite repeat markers at 10 cM intervals over the genome was performed by the Center for Inherited Disease Research (CIDR) on 220 Filipino families with 567 affected and 1,109 unaffected family members genotyped. Among the most statistically significant results from analysis of the genome-wide scan data was a 20 cM region at 8p11-23 in which markers had LODs > or =1.0. This region on 8p11-23 has not been found in any previous genome wide scan nor does it contain any of the candidate genes widely studied in CLP. Fine mapping in 8p11-23 was done in the 220 families plus an additional 51 families, using SNP markers from 10 known genes (FGFR1, NRG1, FZD3, SLC8A1, PPP3CC, EPHX2, BNIP3L, EGR3, PPP2R2A, and NAT1) within the 20 cM region of 8p11-23. Linkage and association analyses of these SNPs yield suggestive results for markers in FGFR1 (recessive multipoint HLOD 1.07) and BAG4 (recessive multipoint HLOD 1.31).
孤立性或非综合征性唇腭裂（NS CLP）是一种由多种遗传和环境因素导致的复杂疾病。在菲律宾，NS CLP的出生患病率为每500人中有1例，那里的大家庭为基因定位提供了机会。遗传性疾病研究中心（CIDR）对220个菲律宾家庭进行了基因组扫描，这些家庭中有567名受影响家庭成员和1109名未受影响家庭成员进行了基因分型，扫描间隔为10厘摩，共检测了392个微卫星重复标记。全基因组扫描数据分析中最具统计学意义的结果之一是8p11 - 23区域有一个20厘摩的区域，其中标记的对数优势比（LOD）≥1.0。此前在任何全基因组扫描中均未发现8p11 - 23上的这个区域，该区域也不包含任何在唇腭裂研究中广泛研究的候选基因。在这220个家庭以及另外51个家庭中，利用8p11 - 23区域20厘摩范围内10个已知基因（FGFR1、NRG1、FZD3、SLC8A1、PPP3CC、EPHX2、BNIP3L、EGR3、PPP2R2A和NAT1）的单核苷酸多态性（SNP）标记，对8p11 - 23进行了精细定位。这些SNP的连锁和关联分析对FGFR1（隐性多点HLOD为1.07）和BAG4（隐性多点HLOD为1.31）中的标记产生了提示性结果。
