Abstract
Developmental dyslexia, or reading disability, is a multigenic complex disease for which at least five loci, i.e. DYX1–3 and DYX5–6, have been clearly identified from the human genome. To date, DYX1C1 is the only dyslexia candidate gene cloned. We have previously reported linkage to 2p11 and 7q32 in 11 Finnish pedigrees. Here, we report the fine mapping of the approximately 40-cM linked region from chromosome 2 as we increased marker density to one per 1.8 cM. Linkage was supported with the highest NPL score of 3.0 (P=0.001) for marker D2S2216. Association analysis using the six pedigrees showing linkage pointed to marker D2S286/rs3220265 (P value <0.001) in the near vicinity of D2S2216. We went on to further characterise this ~15-cM candidate region (D2S2110-D2S2181) by adding six SNPs covering ~670 kb centred at D2S286/rs3220265. A haplotype pattern could no longer be observed in this region, which was therefore excluded from the candidate area. This also excluded the TACR1 (tachykinin receptor 1) gene, located at marker D2S286. The dyslexia candidate region on 2p11 is, therefore, now limited to the chromosomal area D2S2116-D2S2181, which is ~12 Mbp of human sequence and is at a distinct location from the previously reported DYX3 locus, raising the possibility of two distinct loci on chromosome 2p.
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Acknowledgements
We thank Dr. Cecilia Lindgren for her valuable comments on the manuscript and for supervising the SNP genotyping work at the Mutation Analysis Facility (MAF), Clinical Research Center, Huddinge Hospital, Sweden. This work was supported by the Sigrid Jusélius Foundation, the Academy of Finland and the Swedish Medical Research Council (“Vetenskapsrådet”).
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H. Anthoni and P. Onkamo contributed equally to this work
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Peyrard-Janvid, M., Anthoni, H., Onkamo, P. et al. Fine mapping of the 2p11 dyslexia locus and exclusion of TACR1 as a candidate gene. Hum Genet 114, 510–516 (2004). https://doi.org/10.1007/s00439-004-1103-0
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DOI: https://doi.org/10.1007/s00439-004-1103-0