Identifying migraine gene mutations in a large genetic isolate pedigree population.
Migraine is a complex, debilitating neurovascular disease that imparts considerable economic and social burdens on sufferers and their families. The disorder is common in westernised countries – approx 12%, and shows a marked female preponderance (~3:1). A tendency for migraine to run in families also suggests a strong genetic influence on the disorder. We have been involved in migraine genetic studies for over 15 years and our group was the first to map a common migraine gene, and has subsequently identified a number of genes that influence migraine susceptibility.
Recently we undertook a genetic study of the large pedigree from Norfolk Island – in which ancestry can be traced back to the ‘Bounty’ mutineers and Tahitian women who were the original founders of the population. The Norfolk Island population is uniquely suited for pedigree based studies of migraine not only due to the relationships of the cohort but also due to the high number of migraine sufferers. Migraine prevalence was determined to be 25.5% in this population, compared to 12% seen in general populations, interestingly the female preponderance remained consistent in the Norfolk population.
Using this population cohort, we recently identified a novel migraine locus on the X chromosome in a large pedigree from the Norfolk Island genetic isolate. This locus contains a potential migraine candidate gene – the Hephaestin gene, which is in involved in iron transport. We now propose to undertake a study to deep sequence this susceptibility region to further investigate this chromosomal region. The objective of this project is to follow-on from our Norfolk X chromosome study by completely sequencing the Hephaestin gene in migraineurs from the Norfolk Island pedigree in an effort to identify functionally relevant genetic variants associated with migraine predisposition in this and also other migraine populations.