LINGUISTIC PHENOTYPE IN FAMILIAL DYSLEXIA

拟议研究的重点是继续进行基因分型和 常染色体显性遗传家系的表型研究 阅读障碍的显性传递。阅读困难症与 15号染色体标记在这些家族中的一些中，但在 其他的，表明基因的异质性。 该项目的具体长期目标是(1)实现更多 精确定位15号染色体上的阅读障碍基因 评估是否有第二个主要的阅读障碍部位 未与15号染色体连锁的家族中的另一条染色体；(2) 为了澄清这两个基本语言的发展 阅读障碍者阅读过程的表型和成分 来自这些家族；(3)测试任何表型差异 在不同的遗传性阅读障碍之间；和(4)确定 潜在的语言表型是否具有连续性 从学龄前到成年，如果是这样的话，来确定这是如何 潜在的缺陷会影响不同年龄的阅读过程。 因为发展研究的独特优势在 有共同病因的阅读障碍家庭，拟议的研究 将为整个阅读障碍的发展提供一个更加清晰的图景 比以前可能的寿命更长。 实现这些目标将导致更清晰、更科学的 了解一个(或多个)主效基因对 人类认知的特定和具有文化意义的方面。 临床上，这样的理解将形成一口井的基础- 早期识别和治疗这种疾病的根基方法 常见的发育障碍。 为实现这些目标而提出的方法 包括(1)新旧两方面的持续联系研究 与雪莉·史密斯和比尔·金伯林合作的家庭 奥马哈；(2)对两个潜在的 英语阅读过程中的语言表型和成分 来自这些家庭的青少年和儿童阅读障碍；以及(3) 中英潜在语言表型的纵向研究 学龄前儿童确定这种表型的哪一方面 在这些高危家庭中，最有可能出现阅读障碍。

The focus of the proposed research is continued genotype and phenotype studies of families who demonstrate autosomal dominant transmission of dyslexia. Dyslexia is linked to chromosome 15 markers in some of these families, but not in others, indicating genetic heterogeneity. The specific long-term objectives of this project are (1) to more precisely map the dyslexia locus on chromosome 15 and to evaluate whether there is a second major dyslexia locus on another chromosome in families not linked to chromosome 15; (2) to clarify the development of both the underlying linguistic phenotype and components of the reading process in dyslexics from these families; (3) to test for any phenotypic differences between genotypically different dyslexics; and (4) to determine whether there is continuity in the underlying linguistic phenotype from preschool to adulthood, and, if so, to determine how this underlying deficit affects reading processes at different ages. Because of the unique advantages of developmental studies within dyslexic families with a common etiology, the proposed research will yield a much clearer picture of dyslexic development across the life-span than has previously been possible. Achieving these objectives will lead to a clearer, scientific understanding of the effects of one (or more) major genes on a specific and culturally significant aspect of human cognition. Clinically, such an understanding will form the basis of a well- grounded approach to early identification and treatment of this common developmental disorder. The methodology that is proposed to meet these objectives consists of (1) continued linkage studies of both old and new families in collaboration with Shelley Smith and Bill Kimberling in Omaha; (2) a cross-sectional study of both the underlying linguistic phenotype and the components of the reading process in adolescent and child dyslexics from these families; and (3) a longitudinal study of the underlying linguistic phenotype in preschool children to determine which aspect of this phenotype is most predictive of later dyslexia in these high-risk families.