MOLECULAR ANALYSIS OF THE BLOOMS SYNDROME GENE PRODUCT

描述(改编自《调查者摘要》)：布鲁姆综合征 (Bs)是一种罕见的常染色体隐性遗传病，由生长缺陷定义， 免疫缺陷和早发癌症的易感性 类型。早期的研究记录了染色体断裂、重排、 体细胞突变和姐妹染色单体互换率升高 来自受影响个体的细胞。这种高度的基因组不稳定性 导致多个关键基因组位置的突变和高比例的 肿瘤。派的实验室已经分离出布鲁姆综合征基因(BLM) 通过基因作图和位置克隆。一项关于调查的报告 野生型和突变型BLm基因产物的活性将是重要的 在我们对突变基因如何影响临床的理解中 以及人类体细胞中染色体不稳定性是如何发生的。 PI的建议提出了对遗传和生化的研究 BLm基因产物的活性及其利用实验的尝试 酵母遗传学的精确度，开始其功能鉴定。这个 Pi的工作将构成阐明 BLM基因产物在维持人体细胞遗传保真度中的作用 它的突变如何导致布鲁姆综合征的临床表型。

DESCRIPTION (Adapted from the Investigator's Abstract): Bloom's Syndrome (BS) is a rare autosomal recessive disorder defined by growth deficiency, immunodeficiency, and a predisposition to early onset of cancers of all types. Earlier studies documented chromosome breaks, rearrangements, somatic mutations, and an elevated rate of sister-chromatid exchanges in cells from affected individuals. This high level of genomic instability leads to mutations at multiple critical genomic sites and the high rate of neoplasia. The PI's laboratory has isolated the Bloom's Syndrome gene (BLM) by genetic mapping and positional cloning. An investigation of the activities of the wild-type and mutant BLM gene products will be important in our understanding of how the mutated genes influence the clinical phenotype and how chromosome instability occurs in human somatic cells. The PI's proposal presents investigations into the genetic and biochemical activities of the BLM gene product and an attempt to use the experimental precision of yeast genetics to begin its functional characterization. The PI's work will constitute the first steps toward elucidating the role of the BLM gene product in maintaining genetic fidelity in human somatic cells and how its mutation leads to the clinical phenotype of Bloom's Syndrome.