Specific Language Impairment Genetic Research in Extended Pedigrees :: The Research Institute at Nationwide Children's Hospital, Columbus, Ohio

Specific Language Impairment Genetic Research in Extended Pedigrees

Specific language impairment (SLI) is an idiopathic neurodevelopmental complex disorder consisting of clinically depressed language ability despite normal hearing, education and intelligence. Approximately 5-7 percentof school age children meet these criteria and represent the largest portion of children receiving special education services within the nation’s public school system costing on average an additional $2400/year per child while incurring less tax revenue due to lost educational opportunities. SLI is consistently heritable, defined either categorically or quantitatively (Bishop et al. 1995; Tomblin and Buckwalter 1998). To date, two genome-wide scans for SLI have been conducted (Bartlett et al. 2002; SLI_Consortium 2002).  In a previous funding period we found compelling evidence for a susceptibility allele within our families selected for SLI on 13q21-22 (Bartlett et al. 2002) with a PPL of 53% (LOD=3.92).  This finding was followed up with a replication PPL of 17 percent (LOD=2.62) (Bartlett et al. 2004); joint analysis of both datasets shows strong evidence for linkage to 13q21 with a PPL of 96.9 percent (LOD=7.86).  We are executing a series of complementary approaches to assist in understanding the highly complex interrelationships between language and reading measures and how those relationships may underlie the SLI.  To this end we are employing new multivariate approaches which are expected to 1) improve our understanding of how quantitative language and reading measures, some perhaps representing different etiologic mechanisms, relate to SLI as a diagnosis and 2) increase power to detect novel loci.  Our strong linkage signal on 13q21 provides a solid foundation to perform a series of linkage/association analyses using uni- and multi-variate phenotypes including both categorical affection status and quantitative measures of language and related skills in order to dissect the multiple, heterogeneous, pathways to an SLI diagnosis.

Funding:

NIH  R01 DC009453 (Christopher Bartlett, PI)
Total funding: $3,501,664

Project Members:

- Steve Petrill, PhD
- Christopher Bartlett, PhD
- Mike Goode
- Ning Li, PhD

Nationwide Children's Hospital
700 Children's Drive Columbus, Ohio 43205 614.722.2000