Schröck E, Badger P, Larson D, Erdos M, Wynshaw-Boris A, Ried T, Brody L
Diagnostic Development Branch, National Center for Human Genome Research/NIH, Bethesda, MD 20892-4470, USA.
Hum Genet. 1996 Feb;97(2):256-9. doi: 10.1007/BF02265277.
The recently cloned human breast and ovarian cancer susceptibility gene, BRCA1, is located on human chromosome 17q21. We have isolated murine genomic clones containing Brca1 as a first step in generating a mouse model for the loss of BRCA1 function. A mouse genomic library was screened using probes corresponding to exon 11 of the human BRCA1 gene. Two overlapping mouse clones were identified that hybridized to human BRCA1 exons 9-12. Sequence analysis of 1.4 kb of the region of these clones corresponding to part of human exon 11 revealed 72% nucleic acid identity but only 50% amino acid identity with the human gene. The longest of the mouse Brca1 genomic clones maps to chromosome 11D, as determined by two-color fluorescence in situ hybridization. The synteny to human chromosome 17 was confirmed by cohybridization with the mouse probe for the NF1-gene. This comparative study confirms that the relative location of the BRCA1 gene has been conserved between mice and humans.
最近克隆出的人类乳腺癌和卵巢癌易感基因BRCA1,位于人类第17号染色体的q21区域。我们已分离出含有Brca1的小鼠基因组克隆,这是构建BRCA1功能缺失小鼠模型的第一步。使用与人类BRCA1基因第11外显子对应的探针筛选小鼠基因组文库。鉴定出两个与人类BRCA1第9至12外显子杂交的重叠小鼠克隆。对这些克隆中对应人类第11外显子部分区域的1.4 kb进行序列分析,结果显示与人类基因的核酸同一性为72%,但氨基酸同一性仅为50%。通过双色荧光原位杂交确定,最长的小鼠Brca1基因组克隆定位于第11号染色体的D区。通过与小鼠NF1基因探针共杂交,证实了与人类第17号染色体的同线性。这项比较研究证实,BRCA1基因的相对位置在小鼠和人类之间是保守的。