Abstract
The recently cloned human breast and ovarian cancer suseptibility gene,BRCA1, is located on human chromosome 17q21. We have isolated murine genomic clones containingBrca1 as a first step in generating a mouse model for the loss ofBRCA1 function. A mouse genomic library was screened using probes corresponding to exon 11 of the humanBRCA1 gene. Two overlapping mouse clones were identified that hybridized to humanBRCA1 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 mouseBrca1 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 theBRCA1 gene has been conserved between mice and humans.
This is a preview of subscription content, log in via an institution to check access.
References
Barch MJ (1991) The ACT Cytogenetics Laboratory Manual. Association of Cytogenetic Technologists. 2dnd edn. Raven Press, New York
Bernards A, Snijders A, Hannigan G, Murthy A, Gusella J (1994). Mouse neurofibromatosis type 1 cDNA sequence reveals high degree of conservation of both coding and non-coding mRNA segments. Hum Mot Genet 2:645–650
Easton D, Bishop D, Ford D, Crockford G, the Breast Cancer Linkage Consortium (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am J Hum Genet 52:678–701
Fain PR, Goldgar DE, Wallace MR, Collins FS, Wright E, Nguyen K, Barker DF (1989) Refined physical and genetic mapping of the NF1 region on chromosome 17. Am J Hum Genet 45:721–728
Futreal P, Lui Q, Shattuck-Eidens D, Cochran C, Harshman K, Tavtigian S, Benett LM, Haugen-Strano A, Swenson J, Miki Y (1994) BRCA1 mutations in primary breast and ovarian carcinomas. Science 266:120–122
Li W-H, Wu C-I, Luo C-C (1985) A new method for estimating synonymous and non synonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol 2:150–174
Lossie AC, MacPhee M, Buchberg AM, Camper SA (1994) Mouse chromosome II. Mamm Genome 5:S164-S180
Marquis ST, Rajan JV, Wynshaw-Boris A, Xu J, Yin G-Y, Abel KF, Weber BL, Chodosh LA (1995) BRCA1: developmental pattern of expression and modulation by ovarian hormones implies a role in differentiation of the breast and other tissues. Nature Genet 11: 17–26
Marshall E (1993) A statistical portrait of breast cancer. Science 259:619
Miki Y, Swensen J, Shattuck-Eidens D, Futreal A, Harshman K, Tavtigian S, Lui Q, Cochran C, Benett LM, Ding W (1994) A strong canidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71
Ried T, Baldim A, Rand TC, Ward DC (1992) Simultaneous visualization of seven different DNA probes by in situ hybridization using combinatorial fluorescence and digital imaging microscopy. Proc Natl Acad Sci USA 89:1388–1392
Shattuck-Eidens D, McClure M, Simard J, et al (1995) A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. JAMA 273:535–541
Wolfe KH, Sharp PM (1993) Mammalian gene evolution: nucleotide sequence divergence between mouse and rat. J Mol Evol 37:441–456
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schröck, E., Badger, P., Larson, D. et al. The murine homolog of the human breast and ovarian cancer susceptibility geneBrca1 maps to mouse chromosome 11D. Hum Genet 97, 256–259 (1996). https://doi.org/10.1007/BF02265277
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02265277