A typical migraine susceptibility region localizes to chromosome 1q31 |
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Authors: | Lea Rod A Shepherd A Graeme Curtain Robert P Nyholt Dale R Quinlan Sharon Brimage Peter J Griffiths Lyn R |
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Institution: | (1) Genomics Research Centre, School of Health Sciences, Griffith University, Parklands Drive, Southport, Queensland, Australia 4217,;(2) Centre for Molecular and Cellular Biology, University of Queensland, St Lucia, Queensland, Australia,;(3) Queensland Institute of Medical Research, Queensland, Australia,;(4) Institute of Neurological Sciences, Prince of Wales Hospital, Sydney, Australia, |
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Abstract: | Migraine (with and without aura) is a prevalent neurovascular disease that shows strong familial aggregation, although the
number of genes involved and the mode of inheritance is not clear. Some insight into the disease has been gained from genetic
studies into a rare and very severe migraine subtype known as familial hemiplegic migraine (FHM). In this study, we took a
family-based linkage and association approach to investigate the FHM susceptibility region on chromosome 1q31 for involvement
in typical migraine susceptibility in affected Australian pedigrees. Initial multipoint ALLEGRO analysis provided strong evidence
for linkage of Chr1q31 markers to typical migraine in a large multigenerational pedigree. The 1-LOD* unit support interval
for suggestive linkage spanned approximately 18 cM with a maximum allele sharing LOD* score of 3.36 obtained for marker D1S2782
(P=0.00004). Subsequent analysis of an independent sample of 82 affected pedigrees added support to the initial findings with
a maximum LOD* of 1.24 (P=0.008). Utilising the independent sample of 82 pedigrees, we also performed a family-based association test. Results of this
analysis indicated distortion of allele transmission at marker D1S249 global χ2
(5) of 15.00, P=0.010] in these pedigrees. These positive linkage and association results will need further confirmation by independent researchers.
However, overall they provide good evidence for the existence of a typical migraine locus near these markers on Chr1q31, and
reinforce the idea that an FHM gene in this genomic region may also contribute to susceptibility to the more common forms
of migraine.
Electronic Publication |
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Keywords: | Migraine Gene Linkage Association |
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