Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-12-14
pubmed:abstractText
Microindels, defined as mutations that result in a colocalized microinsertion and microdeletion with a net gain or loss of between 1 and 50 nucleotides, may be an important contributor to cancer. We report the first comprehensive analysis of somatic microindels. Our large database of mutations in the lacI transgene of Big Blue((R)) mice contains 0.5% microindels, 2.8% pure microinsertions, and 11.5% pure microdeletions. There appears to be no age, gender, or tissue-type specificity in the frequency of microindels. Of the independent somatic mutations that result in a net in-frame insertion or deletion, microindels are responsible for 13% of protein expansions and 6% of protein contractions. These in-frame microindels may play a crucial role in oncogenesis and evolution via "protein tinkering" (i.e., modest expansion or contraction of proteins). Four characteristics suggest that microindels are caused by unique mechanisms, not just simple combinations of the same mechanisms that cause pure microinsertions and pure microdeletions. First, microinsertions and microdeletions commonly occur at hotspots, but none of the 30 microindels are recurrent. Second, the sizes of the deletions and insertions in microindels are larger and more varied than in pure microdeletions and pure microinsertions. Third, microinsertions overwhelmingly repeat the adjacent base (97%) while the insertions in microindels do so only infrequently (17%). Fourth, analysis of the sequence contexts of microindels is consistent with unique mechanisms including recruitment of translesion DNA synthesis polymerases. The mouse somatic microindels have characteristics similar to those of human germline microindels, consistent with similar causative mechanisms in mouse and human, and in soma and germline.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
Published 2006 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
69-80
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16977595-Age Factors, pubmed-meshheading:16977595-Animals, pubmed-meshheading:16977595-Bacterial Proteins, pubmed-meshheading:16977595-Base Sequence, pubmed-meshheading:16977595-Eukaryotic Cells, pubmed-meshheading:16977595-Female, pubmed-meshheading:16977595-Gene Deletion, pubmed-meshheading:16977595-Germ Cells, pubmed-meshheading:16977595-Germ-Line Mutation, pubmed-meshheading:16977595-Humans, pubmed-meshheading:16977595-Lac Repressors, pubmed-meshheading:16977595-Male, pubmed-meshheading:16977595-Mice, pubmed-meshheading:16977595-Mice, Transgenic, pubmed-meshheading:16977595-Molecular Sequence Data, pubmed-meshheading:16977595-Mutagenesis, Insertional, pubmed-meshheading:16977595-Mutation, pubmed-meshheading:16977595-Nucleic Acid Conformation, pubmed-meshheading:16977595-Organ Specificity, pubmed-meshheading:16977595-Repressor Proteins, pubmed-meshheading:16977595-Sequence Analysis, DNA, pubmed-meshheading:16977595-Sex Characteristics
pubmed:year
2007
pubmed:articleTitle
Somatic microindels: analysis in mouse soma and comparison with the human germline.
pubmed:affiliation
Department of Molecular Genetics, City of Hope National Medical Center, Duarte, California.
pubmed:publicationType
Journal Article, Comparative Study