Evidence for mutation showers.

Evidence for mutation showers. Research Abstract Details 

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Evidence for mutation showers. Abstract Text:

Mutants in the Big Blue transgenic mouse system show spontaneous clustered multiple mutations with unexpectedly high frequency, consistent with chronocoordinate events. We tested the prediction that the multiple mutations seen within the lacI mutation target sometimes occur in the context of chronocoordinate multiple mutations spanning multiple kilobases (mutation showers). Additional sequencing of mutants was performed in regions immediately flanking the lacI region (total of 10.7 kb). Nineteen additional mutations were found outside the lacI region ("ectomutations") from 10 mutants containing two or more lacI mutations, whereas only one ectomutation was found in 130 mutants with a single mutation (P < 0.0001). The mutation showers had an average of approximately one mutation per 3 kb. Four mutants showed closely spaced double mutations in the new sequence, and analysis of the spacing between these mutations revealed significant clustering (P = 0.0098). To determine the extent of the mutation showers, regions (8.5 kb total) remote from the lacI region (approximately 16-17 kb away) were sequenced. Only two additional ectomutations were found in these remote regions, consistent with mutation showers that generally do not extend more than approximately 30 kb. We conclude that mutation showers exist and that they constitute at least 0.2% and possibly 1% or more of mutational events observed in this system. The existence of mutation showers has implications for oncogenesis and evolution, raising the possibilities of "cancer in an instant" and "introns as sponges to reduce the deleterious impact of mutation showers."

Evidence for mutation showers. Publishing Authors By Initials

For similar proteins: transcription factors: repressor proteins research abstracts see: proteins: transcription factors: repressor proteins research

PUBMED ID PMID:

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Evidence for mutation showers. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 8403-8

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 7

MONTH: 05

YEAR: 2007

Evidence for mutation showers. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Evidence for mutation showers. Keywords Mesh Terms:

KEYWORDS: Repressor Proteins

MESH TERMS: genetics

Chemical & Substance for Abstract: Evidence for mutation showers. Information

Substance Name: Repressor Proteins

Registry Number: 0

Grant and Affiliation Information for Evidence for mutation showers.

AFFILIATION: Department of Molecular Genetics and Bioinformatics Group, Department of Molecular Genetics, City of Hope National Medical Center, Duarte, CA 91010, USA.

Country: United States

AGENCY: United States NIA

GRANT: R01 AG 19784

ACRONYM: AG

MEDLINETA: Proc Natl Acad Sci U S A

REFSOURCE: Proc Natl Acad Sci U S A. 2007 May 15;10

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