A genomewide scan identifies two novel loci involved in specific language impairment

摘要: Approximately 4% of English-speaking children are affected by specific language impairment (SLI), a disorder in the development skills despite adequate opportunity and normal intelligence. Several studies have indicated importance genetic factors SLI; positive family history confers an increased risk development, concordance monozygotic twins consistently exceeds that dizygotic twins. However, like many behavioral traits, SLI is assumed to be genetically complex, with several loci contributing overall risk. We compiled 98 families drawn from epidemiological clinical populations, all probands whose standard scores fall > or =1.5 SD below mean for their age. Systematic genomewide quantitative-trait-locus analysis three language-related measures (i.e., Clinical Evaluation Language Fundamentals-Revised [CELF-R] receptive expressive scales nonword repetition [NWR] test) yielded two regions, one on chromosome 16 19, both had maximum LOD 3.55. Simulations suggest that, these multipoint results, NWR linkage 16q most significant, empirical P values reaching 10(-5), under Haseman-Elston (HE) (LOD score 3.55; P=.00003) variance-components (VC) 2.57; P=.00008). Single-point analyses provided further support involvement this locus, markers, peak linkage, yielding >1.9. The 19q locus was linked CELF-R expressive-language threshold suggestive types performed-multipoint HE P=.00004) VC 2.84; P=.00027) single-point 2.49) 2.22). Furthermore, samples showed independent evidence 19q, indicating may represent universally important and, thus, general