Conflation of Short Identity-by-Descent Segments Bias Their Inferred Length Distribution

Abstract

Abstract Identity-by-descent (IBD) is a fundamental concept in genetics with many applications. In a common definition, two haplotypes are said to share an IBD segment if that segment is inherited from a recent shared common ancestor without intervening recombination. Segments several cM long can be efficiently detected by a number of algorithms using high-density SNP array data from a population sample, and there are currently efforts to detect shorter segments from sequencing. Here, we study a problem of identifiability: because existing approaches detect IBD based on contiguous segments of identity-by-state, inferred long segments of IBD may arise from the conflation of smaller, nearby IBD segments. We quantified this effect using coalescent simulations, finding that significant proportions of inferred segments 1–2 cM long are results of conflations of two or more shorter segments, each at least 0.2 cM or longer, under demographic scenarios typical for modern humans for all programs tested. The impact of such conflation is much smaller for longer (> 2 cM) segments. This biases the inferred IBD segment length distribution, and so can affect downstream inferences that depend on the assumption that each segment of IBD derives from a single common ancestor. As an example, we present and analyze an estimator of the de novo mutation rate using IBD segments, and demonstrate that unmodeled conflation leads to underestimates of the ages of the common ancestors on these segments, and hence a significant overestimate of the mutation rate. Understanding the conflation effect in detail will make its correction in future methods more tractable.