Genome Analysis Toolkit

Variant Discovery in High-Throughput Sequencing Data

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Developed in the Data Sciences Platform at the Broad Institute, the toolkit offers a wide variety of tools with a primary focus on variant discovery and genotyping. Its powerful processing engine and high-performance computing features make it capable of taking on projects of any size. Learn more

Case v Control variant comparisons

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    Ricky Magner

    Hi,

    We typically only support technical questions regarding how to use our GATK software, but I'll try to give a few comments about your questions (other users are of course welcome to provide some scientific advice if they wish). 

    1. I'm not familiar with the SnpSift software, but seeing 100% heterozygotes at a site across 120+ individuals does sound a little suspect, especially if this happens at many sites in your cohort. You might be interested in investigating statistics like Excess Heterozygosity if your samples are unrelated. This is somewhat similar to using Hardy-Weinberg equilibrium as a heuristic to measure how the genotype distribution differs from a "population expected" one, when it makes scientific sense, i.e. there's not strong selection pressure against the existence of homozygous variant samples. Being a heterozygote at a site is reference independent, so I don't think this would be related to ancestry or particular references used.

    2. Questions about "scientific legitimacy" are probably better aimed at your research area's community as they can be application specific, but it sounds like you might be interested in functional annotation tools like our Funcotator, which can leverage databases to annotate variants based on existing criteria. I think gnomAD might have labels like missense mutations, etc for common variants you might be able to check out, and possibly save some time in IGV.

    If you have further questions about using our tools, please feel free to post. Thanks!

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