Linked Life Data

1682803

Source:http://linkedlifedata.com/resource/pubmed/id/1682803

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1991-11-27
pubmed:abstractText
Expression of recessive mutant phenotypes can occur by a number of different mechanisms. Inactivation of the wild-type allele by base-substitution mutations, frameshift mutations or small deletions occurs at both hemizygous and heterozygous cellular loci, while other events, such as chromosome level rearrangements, may not be detected at hemizygous loci because of inviability of the resulting mutants. In order to assess the relative contribution of each type of mutational event, we isolated a human lymphoblastoid cell line that is heterozygous at the adenine phosphoribosyltransferase (aprt) locus. The mutation rate for the expression of the mutant phenotype (aprt(+/-)----aprt-/-) was 1.3 x 10(-5)/cell/generation. Molecular analysis of the DNA from 26 mutant clones revealed that 19% had undergone deletion of the entire wild-type allele. The aprt heterozygote carries a mutation in the coding sequence of the gene that results in the loss of a restriction site. Analysis of aprt-/- mutants for this restriction fragment length difference revealed that 23% of the mutants contained point mutations or small (less than 100 bp) deletions. The remainder of the mutants (58%) resulted from reduction to homozygosity of the mutant allele. We suggest that, as in tumor cells in vivo, reduction to homozygosity is a major mechanism for the expression of recessive mutant phenotypes in cultured human cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:volume
250
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
365-74
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
Reduction to homozygosity is the predominant spontaneous mutational event in cultured human lymphoblastoid cells.
pubmed:affiliation
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't