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Chunk #83 — III. Selected Methodological Issues — A. Genotyping using pooled DNAs

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Molecular genetics of addiction and related heritable phenotypes: genome-wide association approaches identify "connectivity constellation" and drug target genes with pleiotropic effects.
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1. DNA quality, quantity and contamination: Care in assessing and maintaining the quantity and quality of DNA in every sample is crucial for pooling studies. Rough DNA quantitation procedures that are routinely used in most genotyping laboratories are likely to introduce such substantial errors that many of the apparent disease/control differences will actually arise from occult over- or under-representation of genotypes of individuals with misquantitated DNAs. Uneven DNA quality can provide the same selective over- and under-representation of genotypes of selected individuals in each pool, leading to more false positives and less sensitivity for detection of true positive results. Contamination of pooled DNA samples with even a modest amount of DNA from laboratory personnel or other sources can also provide difficulties for pooling procedures.