Authors
Tong, PinPrendergast, James G D
Lohan, Amanda J
Farrington, Susan M
Cronin, Simon
Friel, Nial
Bradley, Dan G
Hardiman, Orla
Evans, Alex
Wilson, James F
Loftus, Brendan
Affiliation
Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.Issue Date
2010MeSH
Base SequenceChromosome Mapping
Codon, Nonsense
European Continental Ancestry Group
Gene Duplication
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation
Genome, Human
Geography
Haplotypes
Human Genome Project
Humans
INDEL Mutation
Inflammatory Bowel Diseases
Ireland
Male
Polymorphism, Single Nucleotide
Selection, Genetic
Sequence Analysis, DNA
Metadata
Show full item recordCitation
Sequencing and analysis of an Irish human genome. 2010, 11 (9):R91 Genome Biol.Journal
Genome biologyDOI
10.1186/gb-2010-11-9-r91PubMed ID
20822512Abstract
Recent studies generating complete human sequences from Asian, African and European subgroups have revealed population-specific variation and disease susceptibility loci. Here, choosing a DNA sample from a population of interest due to its relative geographical isolation and genetic impact on further populations, we extend the above studies through the generation of 11-fold coverage of the first Irish human genome sequence.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.
Item Type
ArticleLanguage
enISSN
1465-6914ae974a485f413a2113503eed53cd6c53
10.1186/gb-2010-11-9-r91
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