Reading disability (RD) is a multifactorial heritable disorder defined as difficulty in learning to read despite adequate intelligence and opportunity. It is the most common neurobehavioral disorder affecting children, with a prevalence rate of 10 to 20% accounting for more than 80% of all learning disabilities. While acquisition of skilled reading is to a great extent influenced by important environmental factors such as exposure to print media, story reading, and early childhood education, our group and others have shown that approximately 50% or more of the deficits in RD children can be attributed to inherited factors. Specific risk factors that make a child susceptible to RD are variant alleles of a small number of genes at loci yet to be precisely identified on human chromosome 18, 25, 6, 3, 2, and 2. Clues to the function of these genes may be found in the converging data from functional magnetic resonance imaging (fMRI) studies, which consistently and convincingly show that the normal neural circuitry activated in reading is disrupted in children and adults with RD. We recently confined the location of the strongest-acting of the RD susceptibility loci to a 4 million base region on chromosome 6p through high-resolution studies of linkage disequilibrium in families whose children have RD. Thus, we hypothesize that the 6pRD gene can be identified by an intense genetic analysis of this region using a high-density marker panel in well-characterized cohorts. To address this hypothesis we will: A) Define three RD cohorts for analysis, B) Map the peak of linkage disequilibrium to localize the 6pRD gene, and C) Identify sequence variants in gene-candidates. These studies will take advantage of our experience in gene mapping of the 6p region and our experience in characterizing RD. We anticipate that these studies will lead to the identification of a gene that plays a role in the pathogenesis of RD.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Biobehavioral and Behavioral Processes 3 (BBBP)
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Leblanc, Gabrielle G
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Yale University
Schools of Medicine
New Haven
United States
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DeMille, Mellissa M C; Tang, Kevin; Mehta, Chintan M et al. (2018) Worldwide distribution of the DCDC2 READ1 regulatory element and its relationship with phoneme variation across languages. Proc Natl Acad Sci U S A 115:4951-4956
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