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

中文翻译：

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全基因组扫描可识别涉及特定语言障碍的两个新基因座。

尽管有足够的机会和正常的智力，大约4％的英语儿童会受到特殊语言障碍（SLI）的影响，这是一种语言技能发展障碍。多项研究表明遗传因素在SLI中的重要性。积极的家族史会增加患病的风险，单卵双生双胞胎的一致性始终超过双卵双生双胞胎的一致性。但是，像许多行为特征一样，SLI被认为是遗传上复杂的，有多个基因座导致了整体风险。我们从流行病学和临床人群中收集了98个家庭，所有这些家庭的先证者的标准语言得分低于其年龄平均值的均值= 1.5 SD。系统性的全基因组定量特征位点分析，涉及三种语言相关的指标（即 语言基础修订版[CELF-R]接受和表达量表的临床评估以及非单词重复[NWR]测试）产生两个区域，一个位于16号染色体上，一个位于19号上，两个区域的最大LOD得分均为3.55。模拟表明，在这两个多点结果中，在Haseman-Elston（HE）分析下（LOD得分3.55； P = .00003），与16q染色体的NWR连锁关系最为显着，经验P值达到10（-5）。 ）和方差成分（VC）分析（LOD得分2.57； P = .00008）。单点分析为该基因座的参与提供了进一步的支持，在连锁峰下具有三个标记，LOD得分> 1.9。19q基因位点与CELF-R表达语言得分相关联，并且在进行的所有类型的分析下均超过了提示性链接的阈值-多点HE分析（LOD得分3.55；经验值P = .00004）和VC（LOD得分2.84；经验值） P = .00027）和单点HE分析（LOD得分2.49）和VC（LOD得分2.22）。此外，临床和流行病学样本均显示了16q染色体和19q染色体上连锁的独立证据，表明它们可能代表了SLI中普遍重要的基因座，因此，也是语言障碍的一般危险因素。