CORRELATION OF PHENOTYPE AND CHROMOSOMAL ABNORMALITIES

这项拟议的研究将结合细胞遗传学和分子技术。 确定缺失、重复和标记染色体的特征，并 相关的分子和表型变异。我们将测试 假设出现结构异常的染色体 在细胞学上相似，实际上在分子上不同，我们将 比较可能的结构DNA差异以阐明临床 部分核型相似的患者表现出的异常 异常现象。具体地说，我们将：1)分子表征和 确定性染色体标记的染色体来源。2) 卫星常染色体标记，特别强调inv DUP(15) 染色体。3)常染色体非随体遗传的染色体起源 用于确定是否另外存在任何等色性物质的标记 对检测到的着丝粒物质4)的断点和量 染色体9p缺失患者的染色体材料缺失5) 细微疾病患者染色体材料缺失/复制的数量 删除/复制6)如果染色体材料丢失且 在患有其他疾病的患者中删除或复制此类材料的数量 上面没有描述的重新安排。 一般来说，有三组不同的个体带有染色体 更改将被研究：(1)通过先证者确定的家庭 有表型异常；(2)有额外或缺失的家系 染色体材料，但无表型异常；和(3) 具有未知表型的染色体异常的个体 (即，通过产前诊断确定)。至少100-150 带有标记染色体或从头重排的先证者将被 学习。

This proposed study will combine cytogenetic and molecular techniques to characterize deletions, duplications and marker chromosomes, and to correlate molecular and phenotypic variability. We will test the hypothesis that structurally abnormal chromosomes which appear cytologically similar, are in fact molecularly different, and we will compare possible structural DNA differences to clarify the clinical abnormalities manifested by some of the patients with similar karyotypic abnormalities. Specifically we will: 1) molecularly characterize and determine the chromosomal origin of sex chromosome markers. 2) satellited autosomal markers, with particular emphasis on inv dup (15) chromosomes. 3) the chromosomal origin of autosomal non-satellited markers to determine if any euchromatic material is present in addition to the detected centromeric material 4) the breakpoint and amount of chromosome material missing in chromosome 9p deletion patients 5) the amount of chromosome material deleted/duplicated in patients with subtle deletions/duplications 6) if chromosomal material is missing and the amount of such material deleted or duplicated in patients with other rearrangements not delineated above. In general, three separate groups of individuals with chromosome alterations will be studied: (1) families ascertained via a propositus with phenotypic abnormalities; (2) families with extra or missing chromosomal material, but with no phenotypic abnormalities; and (3) individuals with a chromosome abnormality with a yet unknown phenotype (i.e., ascertained through prenatal diagnosis). A minimum of 100-150 probands with marker chromosomes or de novo rearrangements will be studied.