The projects in the Colorado Learning Disabilities Research Center are focused on the characterization of reading disabilities (RD) and ADHD using genetic analyses to define fundamental deficits based on etiology. This task is complicated by genetic heterogeneity (different genes affecting similar phenotypes) and plieotropism (a single gene affecting more than one phenotype). Identification of quantitative trait loci (QTLs) underlying RD and ADHD is critical to validating the genetic influences on the phenotypes examined by the Projects in the CLDRC and to documenting deficits that are influenced by the same QTLs. In particular, the influences of separate loci on RD and ADHD will determine whether the comorbidity of these disorders is due to the co-segregation of independent loci, or if some loci affect both conditions. We will also be able to determine if certain loci contribute significantly to variation in response to intervention. While there have been many reports of linkage of chromosomal loci to RD and to ADHD, only a few of these have been replicated, and many of the regions of linkage are quite large. The size of our population and the depth of the phenotypic analysis is allowing us to verify candidate loci, characterize their phenotypes, and narrow the critical region sufficiently to identify candidate genes. Discovery of mutations that affect the structure or regulation of the gene product will be strong evidence that a gene has a causal role, and knowledge of the function of such genes will lead to understanding of the neurological mechanisms underlying the processes of reading and attention. This detailed genetic and phenotypic information, along with the corresponding measures of response to intervention, will ultimately contribute to the development of more effective methods of treatment.
