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. 2003 Jan;72(1):161-7.
doi: 10.1086/345298. Epub 2002 Dec 9.

A locus for migraine without aura maps on chromosome 14q21.2-q22.3

D Soragna  1 , A Vettori, G Carraro, E Marchioni, G Vazza, S Bellini, R Tupler, F Savoldi, M L Mostacciuolo
Affiliations

A locus for migraine without aura maps on chromosome 14q21.2-q22.3

D Soragna et al. Am J Hum Genet. 2003 Jan.

Abstract

Migraine is a common and disabling neurological disease of unknown origin characterized by a remarkable clinical variability. It shows strong familial aggregation, suggesting that genetic factors are involved in its pathogenesis. Different approaches have been used to elucidate this hereditary component, but a unique transmission model and causative gene(s) have not yet been identified. We report clinical and molecular data from a large Italian pedigree in which migraine without aura (MO) segregates as an autosomal dominant trait. After exclusion of any association between MO and the known familial hemiplegic migraine and migraine with aura loci, we performed a genomewide linkage analysis using 482 polymorphic microsatellite markers. We obtained significant evidence of linkage between the MO phenotype and the marker D14S978 on 14q22.1 (maximum two-point LOD score of 3.70, at a recombination fraction of 0.01). Multipoint parametric analysis (maximum LOD score of 5.25 between markers D14S976 and D14S978) and haplotype construction showed strong evidence of linkage in a region of 10 cM flanked by markers D14S1027 and D14S980 on chromosome 14q21.2-q22.3. These results indicate the first evidence of a genetic locus associated with MO on chromosome 14.

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Figures

Figure 1
Figure 1
MO family pedigree. Individuals available for typing are indicated by the generated genotype data. The disease haplotype for MO is indicated by the blackened bar. Blackened symbols denote affected individuals; unblackened symbols denote unaffected individuals. The arrow indicates the propositus; the asterisks indicate key recombinants (III:4 and IV:10), who determine the critical interval to be 10 cM, flanked by markers D14S1027 and D14S980.
Figure 2
Figure 2
Multipoint localization of MO. Genetic location (distance in cM) is plotted against the multipoint LOD score. The locations of markers used in the multipoint analysis are indicated. A maximum multipoint LOD score of 5.25 was obtained between markers D14S976 and D14S978.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. Genetic Location Database, http://cedar.genetics.soton.ac.uk/public_html/ldb.html (for genetic-linkage distances)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for migraine [MIM 157300], FHM1 [MIM 141500], CACNA1A [MIM 601011], FHM2 [MIM 602481], MFTS [MIM 300125], MGAU [MIM 300125], GCH1 [MIM 600225], SPG3A [MIM 606439], PTGDR [MIM 606687], PTGER2 [MIM 176804], and BMP4 [MIM 112262])
    1. UCSC Human Genome Project Working Draft, http://genome.ucsc.edu/ (for choosing the microsatellite markers on chromosome 14q)

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