Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-12-5
pubmed:databankReference
pubmed:abstractText
De novo LINE-1 (long interspersed element-1, or L1) retrotransposition events are responsible for approximately 1/1,000 disease-causing mutations in humans. Previously, L1.2 was identified as the likely progenitor of a mutagenic insertion in the factor VIII gene in a patient with hemophilia A. It subsequently was shown to be one of a small number of active L1s in the human genome. Here, we demonstrate that L1.2 is present at an intermediate insertion allele frequency in worldwide human populations and that common alleles (L1.2A and L1.2B) exhibit an approximately 16-fold difference in their ability to retrotranspose in cultured human HeLa cells. Chimera analysis revealed that two amino acid substitutions (S1259L and I1220M) downstream of the conserved cysteine-rich motif in L1 open reading frame 2 are largely responsible for the observed reduction in L1.2A retrotransposition efficiency. Thus, common L1 alleles can vary widely in their retrotransposition potential. We propose that such allelic heterogeneity can influence the potential L1 mutational load present in an individual genome.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-10050284, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-10066175, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-10699189, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-10742098, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-10779482, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-10833198, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-10964437, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-11042149, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-11158327, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-11237011, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-11319268, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-11700292, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-11731495, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-12070800, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-12176319, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-12682288, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-12761047, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-12897783, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-1328181, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-1415253, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-1662412, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-1722352, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-2454389, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-2831458, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-3562227, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-3692483, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-7540721, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-7679954, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-7920631, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-8393568, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-8599946, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-8945517, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-8945518, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-8994846, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-9140383, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-9140393, http://linkedlifedata.com/resource/pubmed/commentcorrection/14610717-9312060
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0002-9297
pubmed:author
pubmed:issnType
Print
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1431-7
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Allelic heterogeneity in LINE-1 retrotransposition activity.
pubmed:affiliation
Departments of Human Genetics and Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0618, USA. moranj@umich.edu
pubmed:publicationType
Journal Article, Comparative Study, 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