caa a22 4500 39757410X CHVBK 20180308164850.0 cr unu---uuuuu 161202e199609 xx s 000 0 eng 10.1093/hmg/5.9.1289 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.9.1289 Human, Canine and Murine BRCA1 Genes: Sequence Comparison Among Species [Elektronische Daten] [Csilla I. Szabo, Lori A. Wagner, Leigh V. Francisco, Jared C. Roach, Rhoda Argonza, Mary-Claire King, Elaine A. Ostrander] Five to ten percent of breast cancer in the western world may be attributed to the inheritance of highly penetrant mutations in the breast and ovarian cancer susceptibility gene, BRCA1. The biological function of BRCA1 and factors affecting expressivity, such as gene-environment and gene-gene interactions, may be more effectively studied in appropriate animal models. We report the cloning and sequencing of the canine and murine BRCA1 genes and contrast the sequences with human BRCA1. The amino terminal 120 residues of the gene are >80% identical among the three species. The C-terminus is also highly conserved, containing an 80 amino acid stretch that is over 80% identical. Motifs of likely functional significance are maintained, including the amino terminal RING finger motif (amino acids 24-64) and the granin consensus sequence (1214-1223). The distribution of missense mutations and neutral polymorphisms identified in BRCA1-linked breast cancer suggests that disease associated missense mutations occur at highly conserved residues whereas polymorphisms are in regions of lower conservation. Among eighteen missense mutations with unknown consequences, seven occur in amino acids that are identical across species. Four of these seven (E1219D, A1708E, P1749R and M1775R) are also within conserved domains. Taken together, these data predict regions of the gene which may be critical for normal function. © 1996 Oxford University Press Szabo Csilla I. Division of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195, USA aut Wagner Lori A. Clinical Research Division-M318, 1124 Columbia St., Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA aut Francisco Leigh V. Clinical Research Division-M318, 1124 Columbia St., Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA aut Roach Jared C. Department of Molecular Biotechnology, University of Washington, Seattle, WA 98195, USA aut Argonza Rhoda Division of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195, USA aut King Mary-Claire Division of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195, USA aut Ostrander Elaine A. Clinical Research Division-M318, 1124 Columbia St., Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA aut Human Molecular Genetics Oxford University Press 5/9(1996-09), 1289-1298 0964-6906 5:9<1289 1996 5 hmg https://doi.org/10.1093/hmg/5.9.1289 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.9.1289 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Szabo Csilla I. Division of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Wagner Lori A. Clinical Research Division-M318, 1124 Columbia St., Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA aut NATIONALLICENCE 700 1- Francisco Leigh V. Clinical Research Division-M318, 1124 Columbia St., Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA aut NATIONALLICENCE 700 1- Roach Jared C. Department of Molecular Biotechnology, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Argonza Rhoda Division of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- King Mary-Claire Division of Medical Genetics, Box 357720, University of Washington, Seattle, WA 98195, USA aut NATIONALLICENCE 700 1- Ostrander Elaine A. Clinical Research Division-M318, 1124 Columbia St., Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/9(1996-09), 1289-1298 0964-6906 5:9<1289 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford