The overall theme ofthe CLDRC is the recognition that reading disability, reading comprehension deficits, and attention deficit hyperactivity disorder are complex conditions that result from deficits in multiple component abilities, some of which are independent and some which are shared. In the projects within the CLDRC, these components are characterized by their genetic and developmental characteristics and their interaction with environment. In Project IV, we will also characterize the genetic contributions to these abilifies at the molecular level. We hypothesize that the genes affecting reading, reading comprehension, and attention will be in similar developmental pathways, and that those pathways will help define the neurodevelopmental processes involved in these conditions. Further, we expect that there will be some distinct genetic influences on reading, reading comprehension, and attention, and that there will also be genes that have more universal effects. To identify the contributing genes, we will extend our current association analyses to design targeted DNA sequencing approaches to identify both common and rare variants in well-characterized candidate regions. We will then test whether these same genetic variants (putative mutations) influence reading, reading comprehension and attention in geographically and ethnically diverse populations. The molecular genetic results will tie together the detailed phenotypic studies of the other projects to define the neurodevelopmental etiologies of learning disabilities and then determine how they generalize across populations. This will provide an etiological framework to describe the genetic influences on learning disabilities, with potential therapeutic and diagnostic implications.
The Genomic Analyses project will combine molecular genetic studies with the detailed data on reading, reading comprehension, and ADHD that is being obtained from twins and their families by the other Projects in the Center. Comprehensive DNA sequencing will be used to discover mutations in genes and regulatory regions, with the overall goal of understanding the developmental processes that affect learning disorders.
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