This is a pilot grant to examine the familial and genetic basis of developmental phonology disorders, the most prevalent group of communication disorders in children. The overall goal of this project is to determine if a gene(s) on chromosome 7q31 plays a substantial role in development of phonology disorders in the general population. We will examine ten microsatellite markers encompassing a 5.6 cM region on chromosome 7q31 in 20 families of children with Developmental Apraxia of Speech (DAS) and 20 families of children with developmental phonology disorders identified in a familial study of phonology disorders. A recent study of a single family with DAS in combination with a grammatical deficit found linkage of this phenotype to markers on this 5.6 cM region of chromosome 7q31. This study was the first clear demonstration that susceptibility to speech sound disorders is mediated via genes. We intend to extend these analyses to a more substantive dataset from the general population to determine if the locus on chromosome 7 has a substantial impact in the etiology of developmental phonology disorders. Model-free approaches to genetic linkage analysis based upon juvenile sibling pairs concordant for DAS or developmental phonology disorder will be used to evaluate phenotypic data separately and as a composite. We will use linkage disequilibrium analysis for fine mapping if we obtain evidence for linkage. Family-based association testing methods will be used to evaluate if any of the markers tested are in very close proximity to the gene for apraxia. This application is intended to provide a core for a further, more extensive, acquisition of DAS and developmental phonology disorder phenotype and genotype data. We, ultimately, intend to expand the entire population to include a genome scan and to positionally clone genes for developmental phonology disorders.
| Stein, Catherine M; Lu, Qing; Elston, Robert C et al. (2011) Heritability estimation for speech-sound traits with developmental trajectories. Behav Genet 41:184-91 |
| Miscimarra, L; Stein, C; Millard, C et al. (2007) Further evidence of pleiotropy influencing speech and language: analysis of the DYX8 region. Hum Hered 63:47-58 |
| Stein, Catherine M; Millard, Christopher; Kluge, Amy et al. (2006) Speech sound disorder influenced by a locus in 15q14 region. Behav Genet 36:858-68 |
| Lewis, Barbara A; Freebairn, Lisa A; Hansen, Amy J et al. (2006) Dimensions of early speech sound disorders: A factor analytic study. J Commun Disord 39:139-57 |
| Lewis, Barbara A; Shriberg, Lawrence D; Freebairn, Lisa A et al. (2006) The genetic bases of speech sound disorders: evidence from spoken and written language. J Speech Lang Hear Res 49:1294-312 |
| Lewis, Barbara A; Freebairn, Lisa A; Hansen, Amy et al. (2004) Family pedigrees of children with suspected childhood apraxia of speech. J Commun Disord 37:157-75 |
| Stein, Catherine M; Schick, James H; Gerry Taylor, H et al. (2004) Pleiotropic effects of a chromosome 3 locus on speech-sound disorder and reading. Am J Hum Genet 74:283-97 |
