Method: This IRB approved study carried out a multipoint PPL genome scan for 556 families from five population-groups (Colombia, India, Philippines, China, USA) on 401 microsatellite markers, 10cM apart, genotyped by CIDR. Using the program KELVIN, multipoint PPLs were generated for each group using population-specific genetic maps, and then they were sequentially updated over all groups to produce the composite genome scan.
Result: PPL<0.10 observed for 95% of the genome; 67% of the genome gave evidence against linkage (PPL<0.02). Peak PPL by chromosomal region: 0.60 12p11.2-12; 0.32 15q22; 0.20 8p22-23; 0.18 6q22-23, 2p21, 2q37(q-ter), 1q44.
Conclusion: These findings not only support prior linkage results, particularly confirming the role of ancestry in observed heterogeneity of CL/P, they also provide stronger evidence in favor of novel chromosomal regions and genes. While it is expected that analyses currently underway that incorporate additional phenotypic information along with patterns of linkage disequilibrium will further refine the regions for follow-up and/or fine mapping, the current results demonstrate the potential power of this approach to facilitate identification of genes associated with complex traits.
Keywords: Biostatistics, Cleft lip-palate, Gene Mapping, Genetics and Methodology