Sequencing of an extended pedigree in Western chimpanzees. O. Venn1, I. Turner2, Z. Iqbal1, I. Mathieson1, N. de Groot3, G. McVean1,2 1) Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom; 2) Department of Statistics, University of Oxford, Oxford, Oxfordshire, United Kingdom; 3) Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

   A wide spectrum of processes including crossover, gene conversion, mutation and DNA repair impact genomes from the level of single nucleotide changes to multiple megabases. Although many of these processes have been studied biochemically, their relative genome-wide distributions are not fully characterized. The analysis of genetic variation estimated from high-throughput population sequencing is a potentially powerful approach to study such processes. However, a major challenge in interpreting this information is the detection of erroneous, mis-assembled, or incorrectly genotyped genetic variants. Currently these errors are identified using ad hoc filters, which have limited application for the analysis of de novo mutation events.
    We present an approach to study rare events in large genomes through the whole genome sequencing of a Western chimpanzee, Pan troglodytes verus, pedigree. We sequenced three founder, three F1, and three F2 individuals to a combined mapped coverage of 315x. This combined coverage is utilized effectively because 7/8 of the founder genomes are transmitted at least once, thereby improving precision to identify and validate genomic changes of different types. To detect events we called variants and Indels across the samples using both alignment-based and de novo assembly algorithms. The data enabled 99.2% of sites that are polymorphic across all individuals to be phased unambiguously. By resolving transmission vectors we were able to accurately observe a wide spectrum of genomic changes enabling insight into biological processes. For instance, we describe the impact of meiotic recombination on the chimpanzee genome at crossover, non-crossover, and gene conversion events across the two generations.

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