Genome scan for spelling deficits: effects of verbal IQ on models of transmission and trait gene localization.
Dyslexia is a complex learning disability with evidence for a genetic basis. Strategies that may be useful for dissecting its genetic basis include the study of component phenotypes, which may simplify the underlying genetic complexity, and use of an analytic approach that accounts for the multilocus nature of the trait to guide the investigation and increase power to detect individual loci. Here we present results of a genetic analysis of spelling disability as a component phenotype. Spelling disability is informative in analysis of extended pedigrees because it persists into adulthood. We show that a small number of hypothesized loci are sufficient to explain the inheritance of the trait in our sample, and that each of these loci maps to one of four genomic regions. Individual trait models and locations are a function of whether a verbal IQ adjustment is included, suggesting mediation through both IQ-related and unrelated pathways.
Rubenstein
Kevin
K
Department of Biostatistics, University of Washington, Box 357232, Seattle, WA, USA.
Matsushita
Mark
M
Berninger
Virginia W
VW
Raskind
Wendy H
WH
Wijsman
Ellen M
EM
D000124:Achievement; D000293:Adolescent; D002648:Child; D002874:Chromosome Mapping; D004410:Dyslexia / Q000235:genetics* / Q000523:psychology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D020412:Multifactorial Inheritance; D010641:Phenotype; D040641:Quantitative Trait Loci; D014706:Verbal Learning