Linked Life Data

19685533

Source:http://linkedlifedata.com/resource/pubmed/id/19685533

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-10-5
pubmed:abstractText
Data from diverse organisms suggests that transient hypermutability is a general mutational mechanism with the potential to generate multiple synchronous mutations, a phenomenon probably best exemplified by closely spaced multiple mutations (CSMMs). Here we have attempted to extend the concept of transient hypermutability from somatic cells to the germline, using human inherited disease-causing multiple mutations as a model system. Employing stringent criteria for data inclusion, we have retrospectively identified numerous potential examples of pathogenic CSMMs that exhibit marked similarities to the CSMMs reported in other systems. These examples include (1) eight multiple mutations, each comprising three or more components within a sequence tract of <100 bp; (2) three possible instances of "mutation showers"; and (3) numerous highly informative "homocoordinate" mutations. Using the proportion of CpG substitution as a crude indicator of the relative likelihood of transient hypermutability, we present evidence to suggest that CSMMs comprising at least one pair of mutations separated by < or =100 bp may constitute signatures of transient hypermutability in human genes. Although this analysis extends the generality of the concept of transient hypermutability and provides new insights into what may be considered a novel mechanism of mutagenesis underlying human inherited disease, it has raised serious concerns regarding current practices in mutation screening.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1098-1004
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1435-48
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Closely spaced multiple mutations as potential signatures of transient hypermutability in human genes.
pubmed:affiliation
Institut National de la Santé et de la Recherche Médicale, U613, Brest, France. Jian-Min.Chen@univ-brest.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't