Background: Recent studies generating complete human sequences from Asian, African and European subgroupshave revealed population-specific variation and disease susceptibility loci. Here, choosing a DNA sample from apopulation of interest due to its relative geographical isolation and genetic impact on further populations, weextend the above studies through the generation of 11-fold coverage of the first Irish human genome sequence. Results: Using sequence data from a branch of the European ancestral tree as yet unsequenced, we identifyvariants that may be specific to this population. Through comparisons with HapMap and previous geneticassociation studies, we identified novel disease-associated variants, including a novel nonsense variant putativelyassociated with inflammatory bowel disease. We describe a novel method for improving SNP calling accuracy atlow genome coverage using haplotype information. This analysis has implications for future re-sequencing studiesand validates the imputation of Irish haplotypes using data from the current Human Genome Diversity Cell LinePanel (HGDP-CEPH). Finally, we identify gene duplication events as constituting significant targets of recent positiveselection in the human lineage. Conclusions: 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 similarinitiatives geared towards answering specific biological questions will emerge.
展开▼
