Showing papers by "Chao Xing published in 2005"

Comparison of microsatellites, single-nucleotide polymorphisms (SNPs) and composite markers derived from SNPs in linkage analysis

Abstract: There is growing evidence that a map of dense single-nucleotide polymorphisms (SNPs) can outperform a map of sparse microsatellites for linkage analysis. There is also argument as to whether a clustered SNP map can outperform an evenly spaced SNP map. Using Genetic Analysis Workshop 14 simulated data, we compared for linkage analysis microsatellites, SNPs, and composite markers derived from SNPs. We encoded the composite markers in a two-step approach, in which the maximum identity length contrast method was employed to allow for recombination between loci. A SNP map 2.3 times as dense as a microsatellite map (~2.9 cM compared to ~6.7 cM apart) provided slightly less information content (~0.83 compared to ~0.89). Most inheritance information could be extracted when the SNPs were spaced < 1 cM apart. Comparing the linkage results on using SNPs or composite markers derived from them based on both 3 cM and 0.3 cM resolution maps, we showed that the inter-SNP distance should be kept small (< 1 cM), and that for multipoint linkage analysis the original markers and the derived composite markers had similar power; but for single point linkage analysis the resulting composite markers lead to more power. Considering all factors, such as information content, flexibility of analysis method, map errors, and genotyping errors, a map of clustered SNPs can be an efficient design for a genome-wide linkage scan.

Genetic linkage of systemic lupus erythematosus to 13q32 in African American families with affected male members.

Abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving genetic and environmental factors. Previously, our group showed that SLE females with affected male relatives have higher prevalence of renal disease than SLE females with no affected male relatives in a sample of 372 individuals from 159 families. By adding 392 individuals from 181 new families, we replicated this finding in the largest collection of families with affected males, confirming our hypothesis that multiplex SLE families with at least one affected male member (“male families”) comprise a distinct subpopulation of SLE multiplex families. We studied 64 male families by a genome-wide scan for SLE and found the largest signal (lod=3.08) at 13q32 in 18 African American male families using an affected-relative-pair model-free linkage method. Closer examination of IBD sharing at this region suggested a dominant mode of inheritance. Multipoint model-based linkage analysis generated a lod score of 3.13 in the same chromosomal region with a low-disease allele frequency of 0.0004 and a disease penetrance of 0.5 for the 18 African American male families. We performed fine mapping in these and three additional African American male families and the SLE predisposing locus was localized to a region tightly linked to the marker D13S892. We have therefore confirmed the linkage of SLE to 13q32, which was reported previously, and suggested that an SLE susceptibility gene in this region is specific to predisposition of African Americans to a specific form of SLE, with males at high risk.

Linkage analysis of alcohol dependence using both affected and discordant sib pairs

Abstract: The basic idea of affected-sib-pair (ASP) linkage analysis is to test whether the inheritance pattern of a marker deviates from Mendelian expectation in a sample of ASPs. The test depends on an assumed Mendelian control distribution of the number of marker alleles shared identical by descent (IBD), i.e., 1/4, 1/2, and 1/4 for 2, 1, and 0 allele(s) IBD, respectively. However, Mendelian transmission may not always hold, for example because of inbreeding or meiotic drive at the marker or a nearby locus. A more robust and valid approach is to incorporate discordant-sib-pairs (DSPs) as controls to avoid possible false-positive results. To be robust to deviation from Mendelian transmission, here we analyzed Collaborative Study on the Genetics of Alcoholism data by modifying the ASP LOD score method to contrast the estimated distribution of the number of allele(s) shared IBD by ASPs with that by DSPs, instead of with the expected distribution under the Mendelian assumption. This strategy assesses the difference in IBD sharing between ASPs and the IBD sharing between DSPs. Further, it works better than the conventional LOD score ASP linkage method in these data in the sense of avoiding false-positive linkage evidence.