title: Pleiotropic effects of a chromosome 3 locus on speech-sound disorder and reading.
abstract: Speech-sound disorder (SSD) is a complex behavioral disorder characterized by speech-sound production errors associated with deficits in articulation, phonological processes, and cognitive linguistic processes. SSD is prevalent in childhood and is comorbid with disorders of language, spelling, and reading disability, or dyslexia. Previous research suggests that developmental problems in domains associated with speech and language acquisition place a child at risk for dyslexia. Recent genetic studies have identified several candidate regions for dyslexia, including one on chromosome 3 segregating in a large Finnish pedigree. To explore common genetic influences on SSD and reading, we examined linkage for several quantitative traits to markers in the pericentrometric region of chromosome 3 in 77 families ascertained through a child with SSD. The quantitative scores measured several processes underlying speech-sound production, including phonological memory, phonological representation, articulation, receptive and expressive vocabulary, and reading decoding and comprehension skills. Model-free linkage analysis was followed by identification of sib pairs with linkage and construction of core shared haplotypes. In our multipoint analyses, measures of phonological memory demonstrated the strongest linkage (marker D3S2465, P=5.6 x 10(-5), and marker D3S3716, P=6.8 x 10(-4)). Tests for single-word decoding also demonstrated linkage (real word reading: marker D3S2465, P=.004; nonsense word reading: marker D3S1595, P=.005). The minimum shared haplotype in sib pairs with similar trait values spans 4.9 cM and is bounded by markers D3S3049 and D3S3045. Our results suggest that domains common to SSD and dyslexia are pleiotropically influenced by a putative quantitative trait locus on chromosome 3.
authors.affiliation: Department of Epidemiology and Biostatistics, Rammelkamp Center for Research, Case Western Reserve University, Cleveland, OH 44109, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Stein
authors.forename: James H
authors.initials: JH
authors.lastname: Schick
authors.forename: H
authors.initials: H
authors.lastname: Gerry Taylor
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Shriberg
authors.forename: Christopher
authors.initials: C
authors.lastname: Millard
authors.forename: Amy
authors.initials: A
authors.lastname: Kundtz-Kluge
authors.forename: Karlie
authors.initials: K
authors.lastname: Russo
authors.forename: Nori
authors.initials: N
authors.lastname: Minich
authors.forename: Amy
authors.initials: A
authors.lastname: Hansen
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Freebairn
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Lewis
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
mesh_terms: D001184:Articulation Disorders / Q000235:genetics*; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D004410:Dyslexia / Q000235:genetics*; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007806:Language Disorders / Q000235:genetics*; D040641:Quantitative Trait Loci