AIMS

To test this hypothesis we propose to assess the sensitivity, specificity, positive predictive value, and negative predictive value of DCDC2 allelic variations for reading performance in all 10,000 DNA samples of the ALSPAC epidemiologic collection. These children have been phenotyped with an array of age-appropriate neurocognitive and reading assessments. At a minimum we will attempt to correlate genotypes with quantitative tests of basic word reading (Wechsler Objective Reading Dimension: WORD subtests49), phoneme deletion (Auditory Analysis Test of Rosner and Simon50), and spelling (regular and irregular words). These tests are administered to the ALSPAC cohort at age 7. We will also include IQ assessments at age 8 through the Wechsler Intelligence Scale for Children III51, and other cognitive measures such as language and verbal short-term memory, and Key Stage 1 School Assessments, if available. Furthermore, our on-going lab studies of the developmental biology of DCDC2 and it's role in neuronal migration, and physiology studies through functional imaging studies at the Yale Center for the Study of Learning and Attention, will suggest correlating additional age-appropriate neurocognitive and language measures that are extant in the ALSPAC cohort.

These studies will lead to the development of a sensitive and cost-effective population screening tool that will identify children at-risk for RD before entering school and help to guide strategies for effective early intervention.Moreover, when considered in the context of our parallel studies of gene function and cognitive imaging profiles, they will lead to a comprehensive understanding of the neurodevelopmental processes subserving language, which should further guide the remediation of RD and other learning disorders.