GENOTYPE AND PHENOTYPE ANALYSES OF FAMILIAL DYSLEXIA

提出的研究的总体目标是实现一个更好的

The overall goals of the proposed research are to achieve a better understanding of both the genetics and the phenotype(s) of developmental dyslexia. Genetic heterogeneity appears to be very likely in dyslexia, but key features of the linguistic phenotype appear to be common across etiologies. Whether certain clinical correlates of dyslexia are part of the phenotype(s) is much less clear. The specific aims of this project are (1) to test alternative models of genetic transmission of dyslexia and to obtain better information about both the transmissible phenotype and genetic parameters important of linkage analysis; (2) to more precisely map the dyslexia locus on chromosome 15 and to confirm or disconfirm a second possible locus on chromosome 6 near the HLA region; (3) to screen the genome for other regions which appear to contribute to the dyslexia phenotype(s); (4) to clarify the development of the underlying linguistic phenotype and components of the reading process; (5) to determine which phonological processing deficits are causal predictors of later familial dyslexia; and (6) to determine whether and how apparent clinical correlates of dyslexia are related to the dyslexia phenotype(s). The methodology that is proposed to meet these objectives consists of (1) segregation analyses using POINTER (Lalouel, et al., 1983) of three large samples of dyslexic families; (2) continued linkage studies of 25 large dyslexic families; (3) a sibling pair linkage study using 100 dyslexic DZ twins pairs; (4) a cross -sectional study of the linguistic phenotype in both family and clinic dyslexics; (5) a longitudinal study of the linguistic precursors of reading in preschool children of either high or low familial risk for dyslexia; and (6) longitudinal, cosegregation, and coheritability analyses of apparent clinical correlates of the dyslexia phenotype. Achieving these objectives will lead to a clearer, neuroscientific understanding of the effects of genes on a specific and culturally significant aspect of human cognition. Clinically, this research will contribute to a well-grounded approach to early identification and treatment of this common developmental disorder.