Chissoe S L, Bodenteich A, Wang Y F, Wang Y P, Burian D, Clifton S W, Crabtree J, Freeman A, Iyer K, Jian L
University of Oklahoma, Department of Chemistry and Biochemistry, Norman 73019, USA.
Genomics. 1995 May 1;27(1):67-82. doi: 10.1006/geno.1995.1008.
The complete human BCR gene (152-141 nt) on chromosome 22 and greater than 80% of the human ABL gene (179-512 nt) on chromosome 9 have been sequenced from mapped cosmid and plasmid clones via a shotgun strategy. Because these two chromosomes are translocated with breakpoints within the BCR and ABL genes in Philadelphia chromosome-positive leukemias, knowledge of these sequences also might provide insight into the validity of various theories of chromosomal rearrangements. Comparison of these genes with their cDNA sequences reveal the positions of 23 BCR exons and putative alternative BCR first and second exons, as well as the common ABL exons 2-11, respectively. Additionally, these regions include the alternative ABL first exons 1b and 1a, a new gene 5' to the first ABL exon, and an open reading frame with homology to an EST within the BCR fourth intron. Further analysis reveals an Alu homology of 38.83 and 39.35% for the BCR and ABL genes, respectively, with other repeat elements present to a lesser extent. Four new Philadelphia chromosome translocation breakpoints from chronic myelogenous leukemia patients also were sequenced, and the positions of these and several other previously sequenced breakpoints now have been mapped precisely, although no consistent breakpoint features immediately were apparent. Comparative analysis of genomic sequences encompassing the murine homologues to the human ABL exons 1b and 1a, as well as regions encompassing the ABL exons 2 and 3, reveals that although there is a high degree of homology in their corresponding exons and promoter regions, these two vertebrate species show a striking lack of homology outside these regions.
通过鸟枪法策略，已从定位的黏粒和质粒克隆中对22号染色体上完整的人类BCR基因（152 - 141 nt）以及9号染色体上超过80%的人类ABL基因（179 - 512 nt）进行了测序。由于在费城染色体阳性白血病中，这两条染色体在BCR和ABL基因内发生易位且存在断点，这些序列的知识也可能为各种染色体重排理论的有效性提供见解。将这些基因与其cDNA序列进行比较，分别揭示了23个BCR外显子以及推定的BCR第一和第二外显子的位置，以及常见的ABL外显子2 - 11的位置。此外，这些区域包括ABL第一外显子1b和1a的替代形式、ABL第一外显子上游的一个新基因，以及BCR第四内含子内与一个EST具有同源性的开放阅读框。进一步分析显示，BCR和ABL基因与其他重复元件的Alu同源性分别为38.83%和39.35%，其他重复元件的存在程度较低。还对来自慢性粒细胞白血病患者的四个新的费城染色体易位断点进行了测序，尽管没有立即发现一致的断点特征，但这些断点以及其他几个先前测序的断点的位置现在已被精确绘制。对包含人类ABL外显子1b和1a的小鼠同源物的基因组序列，以及包含ABL外显子2和3的区域进行比较分析，结果表明，尽管它们相应的外显子和启动子区域具有高度同源性，但这两个脊椎动物物种在这些区域之外显示出明显缺乏同源性。
