title: Genome scan for loci involved in cleft lip with or without cleft palate, in Chinese multiplex families.
abstract: Cleft lip with or without cleft palate (CL/P) is a common congenital anomaly. Birth prevalences range from 1/500 to 1/1,000 and are consistently higher in Asian populations than in populations of European descent. Therefore, it is of interest to determine whether the CL/P etiological factors in Asian populations differ from those in white populations. A sample of 36 multiplex families were ascertained through probands with CL/P who were from Shanghai. This is the first reported genome-scan study of CL/P in any Asian population. Genotyping of Weber Screening Set 9 (387 short tandem-repeat polymorphisms with average spacing approximately 9 cM [range 1-19 cM]) was performed by the Mammalian Genotyping Service of Marshfield Laboratory. Presented here are the results for the 366 autosomal markers. Linkage between each marker and CL/P was assessed by two-point and multipoint LOD scores, as well as with multipoint heterogeneity LOD scores (HLODs) plus model-free identity-by-descent statistics and the multipoint NPL statistic. In addition, association was assessed via the transmission/disequilibrium test. LOD-score and HLOD calculations were performed under a range of models of inheritance of CL/P. The following regions had positive multipoint results (HLOD > or =1.0 and/or NPL P< or =.05): chromosomes 1 (90-110 cM), 2 (220-250 cM), 3 (130-150 cM), 4 (140-170 cM), 6 (70-100 cM), 18 (110 cM), and 21 (30-50 cM). The most significant multipoint linkage results (HLOD > or =2.0; alpha=0.37) were for chromosomes 3q and 4q. Associations with P< or =.05 were found for loci on chromosomes 3, 5-7, 9, 11, 12, 16, 20, and 21. The most significant association result (P=.009) was found with D16S769 (51 cM).
authors.affiliation: Center for Craniofacial and Dental Genetics, Division of Oral Biology, School of Dental Medicine, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA 15261, USA. marazita@sdmgenetics.pitt.edu
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: L Leigh
authors.initials: LL
authors.lastname: Field
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Rose
authors.initials: R
authors.lastname: Tobias
authors.forename: Brion S
authors.initials: BS
authors.lastname: Maher
authors.forename: Supakit
authors.initials: S
authors.lastname: Peanchitlertkajorn
authors.forename: You-e
authors.initials: YE
authors.lastname: Liu
mesh_terms: D002681:China; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D002894:Chromosomes, Human, Pair 4; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D010375:Pedigree