The Research Projects in the Colorado Learning Disabilities Research Center are focused on thecharacterization of reading disabilities (RD) and ADHD using genetic analyses to define fundamental deficitsbased on etiology. This task is complicated by genetic heterogeneity (different genes affecting the samephenotype) and pleiotropism (a single gene affecting more than one phenotype). The studies in Project IVaddress these problems through identification and detailed phenotypic. characterization of quantitative traitloci (QTLs) underlying RD and ADHD and discovery of mutations in candidate genes. Identification of QTLsis critical to validating the independent genetic contributions to phenotypes examined by the projects in theCLDRC and to documenting deficits that are influenced by the same QTLs. In particular, the influences ofseparate loci on RD and ADHD will determine whether their frequent comorbidity is due to co-segregation ofindependent loci, or if they can have a common genetic, and therefore etiologic, basis. In addition to aidingthe genetic dissection of cognitive abilities, we will also examine genetic influences at a clinical level, testingwhether certain loci contribute to variation in response to intervention. While there have been many reportsof linkage of chromosomal loci to RD and to ADHD, only a few of these have been replicated, and many ofthe regions of linkage are quite large. The size of our population and the depth of the phenotypic analysis willallow us to verify candidate loci, characterize their phenotypes, and narrow the critical region sufficiently toidentify candidate genes. Discovery of mutations that affect the structure or regulation of the gene productwill be strong evidence that a gene has a causal role, and knowledge of the function of such genes will leadto understanding of the neurological mechanisms underlying the processes of reading and attention. Thisdetailed genetic and phenotypic information, along with the corresponding measures of response tointervention, will ultimately contribute to the development of more effective methods of treatment.
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