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Chunk #5 — Methods — DNA Collection and Genotyping

Source
Linkage scan of nicotine dependence in the University of California, San Francisco (UCSF) Family Alcoholism Study.
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Prior to analysis, a number of quality control steps were undertaken to ensure the accuracy of the genotype calls. First, the Pedigree Relationship Statistical Test (PREST) (McPeek and Sun, 2000) software was used to identify sample and pedigree structure errors based on the genotypes for autosomal markers. For those individuals in which a probable error was detected, DNA was reisolated from a stored frozen blood specimen and the genotyping was repeated. If the error could not be resolved, the problematic genotype was subsequently treated as missing. Fifteen families were identified with pedigree structure errors. Five were resolved following re-genotyping. Second, Mendelian errors were identified using the program Pedcheck (O'Connell and Weeks, 1998). When isolated Mendelian errors were observed, the genotypes for the entire family were excluded for the marker yielding the error. Markers exhibiting a high rate of Mendelian errors across families were excluded from subsequent analysis. Pedcheck identified 3104 Mendelian errors resulting in 7714 lost genotypes and the exclusion of one marker. Third, the error-checking algorithm implemented in MERLIN (Abecasis et al., 2002) was used to assess the probability