Department of Nutrition and Food Hygiene, School of Public Health, Peking University Health Science Centre, Beijing 100191, China.
Biomed Environ Sci. 2010 Oct;23(5):363-70. doi: 10.1016/S0895-3988(10)60077-3.
To identify the loci involved in nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Northern Chinese people in Shenyang by using genomewide and interaction linkage scan.
Two multiplex families in Shenyang from North China were ascertained through probands with NSCL/P. Blood of every member was drawn for DNA extraction and analysis. Genotypes were available for 382 autosomal short tandem repeat (STR) markers from the ABI Prism Linkage Mapping Set version 2.5. Linkage between markers and NSCL/P was assessed by 2-point parametric LOD scores, multipoint-heterogeneity parametric LOD scores (HLODs), and multipoint nonparametric linkage score (NPL).
The initial scan suggested linkage on Chromosomes 1, 2, and 15. In subsequent fine mapping, 1q32-q42 showed a maximum multipoint LOD score of 1.9(empirical P=0.013) and an NPL score of 2.35 (empirical P=0.053). For 2p24-p25, the multipoint NPL increased to 2.94 (empirical P=0.007). 2-locus interaction analysis obtained a maximum NPL score of 3.73 (P=0.00078) and a maximum LOD score of 3 for Chromosome 1 (at 221 cM) and Chromosome 2 (at 29 cM).
Both parametric and nonparametric linkage scores greatly increased over the initial linkage scores on 1q32-q42, suggesting a susceptibility locus in this region. Nonparametric linkage gave a strong evidence for a candidate region on chromosome 2p24-p25. The superiority of 2-locus linkage scores compared to single-locus scores gave additional evidence for linkage on 1q32-q42 and 2p24-p25, and suggested that certain genes in the two regions may contribute to NCSL/P risks with interaction.
通过全基因组和相互作用连锁扫描，确定中国沈阳北方人群中非综合征性唇裂伴或不伴腭裂（NSCL/P）的相关基因座。
通过 NSCL/P 先证者在沈阳确定了两个北方的多态性家族。从每位成员中抽取血液进行 DNA 提取和分析。ABI Prism Linkage Mapping Set version 2.5 中的 382 个常染色体短串联重复（STR）标记的基因型可用。通过 2 点参数 LOD 评分、多点异质性参数 LOD 评分（HLOD）和多点非参数连锁评分（NPL）评估标记与 NSCL/P 之间的连锁关系。
初步扫描提示染色体 1、2 和 15 上存在连锁。在随后的精细作图中，1q32-q42 显示出最大的多点 LOD 评分 1.9（经验 P=0.013）和 NPL 评分 2.35（经验 P=0.053）。对于 2p24-p25，多点 NPL 增加到 2.94（经验 P=0.007）。2 个位点相互作用分析获得最大的 NPL 评分 3.73（P=0.00078）和最大的 LOD 评分 3，位于染色体 1（在 221 cM）和染色体 2（在 29 cM）。
参数和非参数连锁评分大大高于 1q32-q42 上的初始连锁评分，表明该区域存在易感基因座。非参数连锁为染色体 2p24-p25 上的候选区域提供了强有力的证据。与单一位点评分相比，2 个位点评分的优势为 1q32-q42 和 2p24-p25 上的连锁提供了额外的证据，并表明这两个区域的某些基因可能通过相互作用导致 NSCL/P 风险。
