SUSCEPTIBILITY LOCI FOR DISTINCT COMPONENTS OF DEVELOPMENTAL DYSLEXIAON CHROMOSOME-6 AND CHROMOSOME-15

Six extended dyslexic families with at least four affected individuals were genotyped with markers in three chromosomal regions: 6p23-p21.3, 15pter-qter, and 16pter-qter. Five theoretically derived phenotypes w ere used in the linkage analyses: (1) phonological awareness; (2) phon ological decoding; (3) rapid automatized naming; (4) single-word readi ng; and (5) discrepancy between intelligence and reading performance, an empirically derived, commonly used phenotype. Two-point and multipo int allele-sharing analyses of chromosome 6 markers revealed significa nt evidence (P < 10(-6)) for linkage of the phonological awareness phe notype to five adjacent markers (D6S109, D6S461, D6S299, D6S464, and D 6S306). The least compelling results were obtained with single-word re ading. In contrast, with chromosome 15 markers, a LOD score of 3.15 wa s obtained for marker D15S143 at theta = 0.0 with single-word reading. Multipoint analyses with markers adjacent to D15S143 (D15S126, D15S13 2, D15S214, and D15S128) were positive, but none reached acceptable si gnificance levels. Chromosome 15 analyses with the phonological awaren ess phenotype were negative. Parametric and nonparametric linkage anal yses with chromosome 16 markers were negative. The most intriguing asp ect of the current findings is that two very distinct reading-related phenotypes, reflecting different levels in the hierarchy of reading-re lated skills, each contributing to different processes, appear to be l inked to two different chromosomal regions.