0000000000173178
AUTHOR
Marco Zucchelli
Fine mapping of the 2p11 dyslexia locus and exclusion of TACR1 as a candidate gene.
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 value0.001) in the near vicinity of D2S2216. We w…
A locus on 2p12 containing the co-regulated MRPL19 and C2ORF3 genes is associated to dyslexia.
DYX3, a locus for dyslexia, resides on chromosome 2p11-p15. We have refined its location on 2p12 to a 157 kb region in two rounds of linkage disequilibrium (LD) mapping in a set of Finnish families. The observed association was replicated in an independent set of 251 German families. Two overlapping risk haplotypes spanning 16 kb were identified in both sample sets separately as well as in a joint analysis. In the German sample set, the odds ratio for the most significantly associated haplotype increased with dyslexia severity from 2.2 to 5.2. The risk haplotypes are located in an intergenic region between FLJ13391 and MRPL19/C2ORF3. As no novel genes could be cloned from this region, we hy…
The Aromatase Gene CYP19A1: Several Genetic and Functional Lines of Evidence Supporting a Role in Reading, Speech and Language
Inspired by the localization, on 15q21.2 of the CYP19A1 gene in the linkage region of speech and language disorders, and a rare translocation in a dyslexic individual that was brought to our attention, we conducted a series of studies on the properties of CYP19A1 as a candidate gene for dyslexia and related conditions. The aromatase enzyme is a member of the cytochrome P450 super family, and it serves several key functions: it catalyzes the conversion of androgens into estrogens; during early mammalian development it controls the differentiation of specific brain areas (e.g. local estrogen synthesis in the hippocampus regulates synaptic plasticity and axonal growth); it is involved in sexua…
Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
The work conducted at the WTCHG was supported by Wellcome Trust grants [076566/Z/05/Z] and [075491/Z/04]; the work in Zurich partly by an SNSF grant [32-108130]. We also thank MAF (Mutation Analysis core Facility) at the Karolinska Institute, Novum, Huddinge. The French part of the project was funded by Agence Nationale de la Recherche (ANR-06-NEURO-019-01 GENEDYS) and Ville de Paris. S Paracchini is a Royal Society University Research Fellow. D Czamara was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy). Dyslexia is one of the most common childhood disorders with a prevalence o…