Chromosome 19p13 loci in Finnish migraine with aura families

Biomedicum Helsinki, Research Program in Molecular Medicine, University of Helsinki, Helsinki, Finland.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.27). 01/2005; 132B(1):85-9. DOI: 10.1002/ajmg.b.30082
Source: PubMed

ABSTRACT Chromosomal area 19p13 contains two migraine associated genes: a Ca(v)2.1 (P/Q-type) calcium channel alpha(1) subunit gene, CACNA1A, and an insulin receptor gene, INSR. Missense mutations in CACNA1A cause a rare Mendelian form of migraine, familial hemiplegic migraine type 1 (FHM1). Contribution of CACNA1A locus has also been studied in the common forms of migraine, migraine with (MA) and without aura (MO), but the results have been contradictory. The role of INSR is less well established: A region on 19p13 separate from CACNA1A was recently reported to be a major locus for migraine and subsequently, the INSR gene was associated with MA and MO. Our aim was to clarify the role of these loci in MA families by analyzing 72 multigenerational Finnish MA families, the largest family sample so far. We hypothesized that the potential major contribution of the 19p13 loci should be detected in a family sample of this size, and this was confirmed by simulations. We genotyped eight polymorphic microsatellite markers surrounding the INSR and CACNA1A genes on 757 individuals. Using parametric and non-parametric linkage analysis, none of the studied markers showed any evidence of linkage to MA either under locus homogeneity or heterogeneity. However, marginally positive lod scores were observed in three families, and thus for these families the results remain inconclusive. The overall conclusion is that our study did not provide evidence of a major MA susceptibility region on 19p13 and thus we were not able to replicate the INSR locus finding.

  • [Show abstract] [Hide abstract]
    ABSTRACT: There are contrary results about the role of CACNA1A gene in the causation of common migraine in different populations. However, migraine may be genetically heterogeneous and more studies in different families and populations are required for a definite conclusion. The aim of this study was to surveyed leukocyte genomic DNA mutation of CACNA1A in Iranian migraine patients with [MA] and without aura [MO] who has family history of migraine and we performed a narrative review of all studies that evaluated CACNA1A gene, non-hemiplegic migraine [MA and MO] and FHM [familial hemiplegic migraine]. The 30 patients with family history of migraine were selected for mutations analysis for CACNA1A gene by PCR method. For review, we searched MEDLINE-PUBMED, ISI, Scopus and Cochrane databases up to December 2012. Mutation analysis of the 4 exons of the CACNA1A gene in these patients revealed no mutations in this gene. Direct sequencing revealed a polymorphism previously reported G to A transition in the exon 16 [nt2369, G→A] in 9 patients. In review, the correlation of FHM loci [CACNA1A gene] with MA and MO has been showed in different population and only small population from Caucasians presented this correlation. CACNA1A is most likely not a major susceptibility gene for common migraine in Iranian maigrainous. It's essential to study more on larger series and covering all 47 exons of the CACNA1A gene to confirm this hypothesis.
    Journal of research in medical sciences 03/2013; 18(Suppl 1):S6-S10. · 0.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PSEUDOMARKER is a software package that performs joint linkage and linkage disequilibriumanalysis between a marker and a putative disease locus. A key feature of PSEUDOMARKER isthat it can combine case-controls and pedigrees of varying structure into a single unified analysis.Thus it maximizes the full likelihood of the data over marker allele frequencies or conditional allelefrequencies on disease and recombination fraction. The new version 2.0 uses the software package NOMAD to maximize likelihoods, resulting in generallycomparable or better optima with many fewer evaluations of the likelihood functions. After being modified substantially to use modern optimization methods, PSEUDOMARKER version2.0 is more robust and substantially faster than version 1.0. NOMAD may be useful in other bioinformaticsproblems where complex likelihood functions are optimized.
    BMC Bioinformatics 02/2014; 15(1):47. DOI:10.1186/1471-2105-15-47 · 2.67 Impact Factor
  • Source