Genome-wide and interaction linkage scan for nonsyndromic cleft lip with or without cleft palate in two multiplex families in Shenyang, China.
OBJECTIVE
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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Department of Nutrition and Food Hygiene, School of Public Health, Peking University Health Science Centre, Beijing 100191, China.
Yun
Y
Wang
Xin
X
Li
Wen-Li
WL
Zhu
Jin-Zhen
JZ
Guo
Xiao-Ming
XM
Song
Shu-Qin
SQ
Li
Yong
Y
Li
D002681:China; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D002971:Cleft Lip / Q000150:complications / Q000235:genetics*; D002972:Cleft Palate / Q000150:complications / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree