Despite a growing body of evidence indicating that speech sound disorder (SSD) has an underlying genetic etiology, researchers have not yet identified specific genes predisposing to this condition. The speech and language deficits associated with SSD are shared with several other disorders, including dyslexia, autism, Prader-Willi Syndrome (PWS), and Angelman's Syndrome (AS), raising the possibility of gene sharing. Furthermore, we previously demonstrated that dyslexia and SSD share genetic susceptibility loci. The present study assesses the hypothesis that SSD also shares susceptibility loci with autism and PWS. To test this hypothesis, we examined linkage between SSD phenotypes and microsatellite markers on the chromosome 15q14-21 region, which has been associated with autism, PWS/AS, and dyslexia. Using SSD as the phenotype, we replicated linkage to the 15q14 region (P=0.004). Further modeling revealed that this locus influenced oral-motor function, articulation and phonological memory, and that linkage at D15S118 was potentially influenced by a parent-of-origin effect (LOD score increase from 0.97 to 2.17, P=0.0633). These results suggest shared genetic determinants in this chromosomal region for SSD, autism, and PWS/AS.

Background/Aims: Genetic studies have raised the possibility of common bases for cognitive linguistic disorders such as speech sound disorder (SSD), reading disorder (RD) and language impairment (LI). Thus, some of the same genes may jointly influence cognitive components within and between these three disorders. We examined the plausibility of this theory in a sample of families ascertained on the basis of a child with SSD. Methods: Using the method of generalized estimating equations to solve a bivariate family predictive model we obtained measures of comorbidity and familial aggregation of SSD and LI. We then used two methods of multipoint model-free linkage analysis to evaluate SSD and LI psychometric test measures over a region previously implicated in linkage studies of RD, DYX8 region, 1p34-p36. Results: Bivariate phenotypic analyses show evidence of comorbidity and within family aggregation and coaggregation of SSD and LI. In addition, two regions on chromosome 1 show suggestive evidence of linkage. The first region was previously reported in dyslexia studies. Our maximum linkage signal in this region measured articulation (p = 0.0009) in SSD sibling pairs. The second region is characterized by processes involved in language production, with the maximum linkage signal measuring listening comprehension (p = 0.0019) using all sibling pairs. Conclusion: We conclude that the DYX8 region could bear genes controlling pleiotropic effects on SSD, LI and RD.

The results documented both residual effects in adulthood of childhood SSD and familial aggregation for SSD. These residual difficulties do not appear to affect educational and occupational outcomes.

Standard genetic mapping techniques scan chromosomal segments for location of genetic linkage and association signals. The majority of these methods consider only correlations at single markers and/or phenotypes with explicit detailing of the genetic structure. These methods tend to be limited by their inability to consider the effect of large numbers of model variables jointly. In contrast, we propose a Bayesian analysis of variance (ANOVA) method to categorize individuals based on similarity of multidimensional profiles and attempt to analyze all variables simultaneously. Using Problem 1 of the Genetic Analysis Workshop 15 data set, we demonstrate the method's utility for joint analysis of gene expression levels and single-nucleotide polymorphism genotypes. We show that the method extracts similar information to that of previous genetic mapping analyses, and suggest extensions of the method for mining unique information not previously found.