title: Absence of significant linkage between phonological coding dyslexia and chromosome 6p23-21.3, as determined by use of quantitative-trait methods: confirmation of qualitative analyses.
abstract: We recently reported the absence of significant linkage of phonological coding dyslexia (PCD) to chromosome 6p23-p21.3 in 79 families with at least two affected siblings, even though linkage of dyslexia to this region has been found in four other independent studies. Whereas, in our previous analyses, we used a qualitative (affected, unaffected, or uncertain) PCD phenotype, here we report a reanalysis of linkage to the chromosome 6p region, by use of four quantitative measures of reading disability: phonological awareness, phonological coding, spelling, and rapid-automatized-naming (RAN) speed. The phonological-coding and spelling measures were highly correlated with each other and with the qualitative PCD phenotype, whereas the phonological-awareness and RAN-speed measures were only moderately correlated with the other measures. Using two-point and multipoint quantitative-trait sib-pair linkage analyses and variance-components analyses, we were unable to detect significant evidence for a locus in the 6p23-p21.3 region influencing any of the quantitative reading measures, supporting our previous qualitative linkage results. The most likely explanation for our inability to detect linkage between dyslexia and this region is that families with subtypes of dyslexia linked to this region are underrepresented in our sample, because of either chance or varying ascertainment criteria.
authors.affiliation: Department of Medical Genetics, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
authors.forename: T L
authors.initials: TL
authors.lastname: Petryshen
authors.forename: B J
authors.initials: BJ
authors.lastname: Kaplan
authors.forename: M F
authors.initials: MF
authors.lastname: Liu
authors.forename: L L
authors.initials: LL
authors.lastname: Field
mesh_terms: D000293:Adolescent; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004410:Dyslexia / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D008126:Lod Score; D016555:Matched-Pair Analysis; D018895:Microsatellite Repeats / Q000235:genetics; D009679:Nuclear Family; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D015203:Reproducibility of Results; D015983:Selection Bias; D012984:Software