eb0da0df-edac-4e4e-995e-f8d46c640f09
title
Fine mapping of the 2p11 dyslexia locus and exclusion of  TACR1  as a candidate gene.
f72f0e84-492b-4f35-9eb5-bad0e55ef190
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 approximately 15-cM candidate region (D2S2110-D2S2181) by adding six SNPs covering approximately 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 approximately 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.