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Candidate gene isolation and comparative analysis of a commonly deleted segment of 7q22 implicated in myeloid malignancies.

机译:候选基因的分离和比较分析涉及髓系恶性肿瘤的7q22的通常删除的部分。

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摘要

Monosomy 7 and deletion of 7q are recurring abnormalities in malignant myeloid diseases. Here we extensively characterize an approximately 2-Mb commonly deleted segment (CDS) of 7q22 bounded by D7S1503 and D7S1841. Approximately 1.8 Mb of sequence have been generated from this interval, facilitating the construction of a transcript map that includes large numbers of genes and ESTs. The intron/exon organization of seven genes and expression patterns of three genes were determined, and leukemia samples were screened for mutations in five genes. We have used polymorphic markers from this region to examine leukemia cells for allelic loss within 7q22. Finally, we isolated mouse genomic clones orthologous to several of the characterized human genes. Fluorescence in situ hybridization studies using these clones indicate that a region of orthologous synteny lies on proximal mouse chromosome 5. These resources should greatly accelerate the pace of candidate gene discovery in this region.
机译:7号单体性和7q缺失是恶性骨髓疾病中反复出现的异常。在这里,我们广泛地描述了由D7S1503和D7S1841界定的7q22的大约2 Mb的普遍缺失片段(CDS)。从该间隔产生了大约1.8 Mb的序列,这有助于构建包含大量基因和EST的转录本。确定了七个基因的内含子/外显子组织和三个基因的表达模式,并筛选了白血病样本中五个基因的突变。我们使用了来自该区域的多态性标记来检查7q22内白血病细胞的等位基因丢失。最后,我们分离了与某些人类基因同源的小鼠基因组克隆。使用这些克隆进行的荧光原位杂交研究表明,直系同源区域位于小鼠近端5号染色体上。这些资源应大大加快该区域候选基因的发现速度。

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