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Chunk #5 — Methods and Materials — Linkage Analysis

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Genome-wide linkage analyses of quantitative and categorical autism subphenotypes.
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The genotypes were obtained using the Affymetrix (Santa Clara, California) 10K single nucleotide polymorphism (SNP) arrays at the Translational Genomics Research Institute (3). Detailed genotyping methods are available at http://www.affymetrix.com/products/arrays/specific/10k.affx, and details of quality control can be found in Supplement 1. A total of 5371 tag SNPs were selected for linkage analyses so that they were not in strong linkage disequilibrium with each other (maximum D' = .6 with a mean distance of .68 cM and SD of 1 cM and a mean minor allele frequency of .31 with SD = .12) (40). The Rutgers genetic map (http://compgen.rutgers.edu/maps/) (41) was used as the basis for linear interpolation for the locations of the Affymetrix 10K SNPs with the physical locations from National Center for Biotechnology Information (NCBI) Build 35 (42). Because Merlin (http://www.sph.umich.edu/csg/abecasis/Merlin/index.html) assumes a no-interference model, the Kosambi map was converted into the Haldane map for linkage analyses while all results were reported on the Kosambi scale. The marker allele frequencies were calculated using the founders from the inferred Caucasian families by Haploview (http://www.broad.mit.edu/mpg/haploview/index.php) (43).