Sequencing and analysis of an Irish human genome

Using sequence data from a branch of the European ancestral tree as yet unsequenced, we identify variants that may be specific to this population. Through comparisons with HapMap and previous genetic association studies, we identified novel disease-associated variants, including a novel nonsense variant putatively associated with inflammatory bowel disease. We describe a novel method for improving SNP calling accuracy at low genome coverage using haplotype information. This analysis has implications for future re-sequencing studies and validates the imputation of Irish haplotypes using data from the current Human Genome Diversity Cell Line Panel (HGDP-CEPH). Finally, we identify gene duplication events as constituting significant targets of recent positive selection in the human lineage.Our findings show that there remains utility in generating whole genome sequences to illustrate both general principles and reveal specific instances of human biology. With increasing access to low cost sequencing we would predict that even armed with the resources of a small research group a number of similar initiatives geared towards answering specific biological questions will emerge.Publication of the first human genome sequence heralded a landmark in human biology [1]. By mapping out the entire genetic blueprint of a human, and as the culmination of a decade long effort by a variety of centers and laboratories from around the world, it represented a significant technical as well as scientific achievement. However, prior the publication, much researcher interest had shifted towards a 'post-genome' era in which the focus would move from the sequencing of genomes to interpreting the primary findings. The genome sequence has indeed prompted a variety of large scale post-genome efforts, including the encyclopedia of DNA elements (ENCODE) project [2], which has pointed towards increased complexity at the levels of the genome and transcriptome. Analysis of this complexity is increasin