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  • Oncogenomics
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Marsupial BRCA1: conserved regions in mammals and the potential effect of missense changes

Oncogene volume 23, pages 1780–1788 (2004)Cite this article

Abstract

More than half of the reported missense changes in the breast cancer susceptibility protein BRCA1 occur in exon 11, but none has been clearly identified as disease associated and only 28 are designated ‘probable’ neutral polymorphisms. Previously, in a comparison of sequences from 57 eutherian mammal species, we found seven ‘highly conserved regions’ between amino acids 282 and 1103, and identified 38 missense changes as likely to disrupt gene function. These conserved regions were also present in birds and amphibians and included only six of the mutations predicted to affect function. In this new analysis, we hypothesized that using 37 ancestral sequences derived from the 57 GenBank sequences and including eight marsupial sequences would allow us to identify regions unique to mammals and refine our predictions of disease-associated missense changes. We identified 13 conserved regions, three of which appear to be unique to mammals, and 21 likely disease-associated missense changes, 11 of which occur in conserved regions. Seven regions identified in this analysis, including the three found only in mammalian sequences, and nine missense changes predicted to affect function are in the putative STAT1-interaction domain, suggesting that the role of STAT1 in immune response is important to mammary function. The reduction in the number of missense changes predicted to be disease associated and the identification of conserved regions specific to mammals can facilitate the further study of the role of missense changes in BRCA1-associated breast cancers.

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Acknowledgements

We thank Dr John AW Kirsch of the University of Wisconsin Zoological Museum for the Virginia opossum tissue sample, Dr Tammie Bettinger of the Cleveland Zoo for red kangaroo and wallaroo blood samples, and Dr Janis Joslin of the Woodland Park Zoo for tree kangaroo blood samples. This work was supported by Grant T32-HG00035 to CJ Ramirez, Grant K05 CA-90754-01 to EA Ostrander, and Grant U24 CA-78164 to JD Potter.

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Authors and Affiliations

  1. Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, 98109-1024, WA, USA

    Christina J Ramirez, Melissa A Fleming & Elaine A Ostrander

  2. Department of Molecular and Cellular Biology, University of Washington, Seattle, 98195, WA, USA

    Christina J Ramirez

  3. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, 98109-1024, WA, USA

    John D Potter

  4. Departments of Biology and Comparative Medicine, Johns Hopkins University, Baltimore, 21218, MD, USA

    Gary K Ostrander

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  1. Christina J Ramirez
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  2. Melissa A Fleming
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Correspondence to Elaine A Ostrander.

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Ramirez, C., Fleming, M., Potter, J. et al. Marsupial BRCA1: conserved regions in mammals and the potential effect of missense changes. Oncogene 23, 1780–1788 (2004). https://doi.org/10.1038/sj.onc.1207292

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