The genome of an Irish man has been fully sequenced for the first time, and reveals a unique 'Irish genetic signature'. Professor Brendan Loftus from the Conway Institute at University College Dublin, who led the study, hopes that the findings will contribute to the understanding of genetic diversity in the human population and help to identify genetic susceptibility to diseases common in the Irish population such as cystic fibrosis, haemochromatosis and phenylketonuria.
Professor Loftus and colleagues sequenced the DNA of an anonymous male from Irish Caucasian ancestry of at least three generations. The individual had previously been involved in genotyping studies and was confirmed to be representative of the Irish population as well as genetically distinct from the British population.
The researchers studied the SNPs (single nucleotide polymorphisms), insertion/deletions (indels) and CNVs (copy number variants) in the individual’s genome and compared these to reference genomes.
The study, published in the journal Genome Biology, identified three million SNP variants and compared to a reference genome, of which 13 per cent were unique to the Irish genome and not previously reported. A number of the SNP variants were identified as disease risk markers associated with genes implicated in inflammatory bowel disease and primary sclerosing cholangitis, a type of chronic liver disease.
The researchers also used data from the sequenced Irish genome and nine other sequenced genomes – from Caucasian, Chinese, Korean and African individuals – to investigate the role of copy number variation in positive selection of genes. They found that where gene duplication has occurred in recent human lineage, both of the new gene paralogs are subject to high levels of positive selection and a high rate of evolution.
The sequenced Irish genome will complement the 1000 genomes project, an international research collaboration in which European genetic diversity is represented by Italian, Spanish, British, Finnish and European American populations.
'Having an Irish genome is important because essentially genes mirror geography in many parts. We are distinct from other Europeans and have our own genetic structure', said Professor Loftus. Dr Gerard Cagney, principal investigator in functional genomics at the Conway Institute, agreed: 'it can be used to place Irish genes in the context of worldwide human genome diversity'.
The sequenced Irish genome also gives insight into the genetic basis of susceptibility to diseases in the Irish population. Professor Loftus also said that, 'the majority of blockbuster drugs, from aspirin to cancer medication, do not appear to work on significant sections of the population… There is a big thrust in the medical community towards personalising medicine and nutrition because people respond in different ways to the same product'.
'And one of the most likely reasons for this is their genetic background. The drug companies are interested to see who these people are, and to find out if they will respond to variations of the existing drug compounds'.