L. Marazita, Mary et al., Genome Scan for Loci Involved in Cleft Lip With or Without Cleft Palate, in Chinese Multiplex Families, American journal of human genetics , 71(2), 2002, pp. 349-364
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 .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 .1.0 and/or NPL P..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 .2.0; .=0.37) were for chromosomes 3q and 4q. Associations with P..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).