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BIRS Workshop Lecture Videos

Inferring rare disease risk variants based on exact probabilities of sharing among multiple affected relatives. Ruczinski, Ingo


Sequencing DNA in extended multiplex families can help to identify high penetrance disease variants too rare in the population to be detected through tests of association in population based studies, but co-segregate with disease in families. When only few affected subjects per family are sequenced, evidence that a rare single nucleotide or copy number variant may be causal can be quantified from the probability of sharing alleles by all affected relatives given it was seen in any one family member under the null hypothesis of complete absence of linkage and association. We present a general framework for calculating such sharing probabilities when two or more affected subjects per family are sequenced, and show how information from multiple families can be combined by calculating a p-value as the sum of the probabilities of sharing events as (or more) extreme. We present case studies from families with multiple members born with oral clefts, and introduce the Bioconductor package RVS.

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