A major insertion accounts for a significant proportion of mutations underlying human lipoprotein lipase deficiency.
- 1 February 1989
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 86 (3) , 948-952
- https://doi.org/10.1073/pnas.86.3.948
Abstract
Lipoprotein lipase (LPL; triacylglyceroprotein acylhydrolase, EC 3.1.1.34) is an important enzyme involved in triacylglycerol metabolism. Primary LPL deficiency is a genetic disorder that is usually manifested by a severe elevation in triacylglycerol levels. We have used a recently isolated LPL cDNA clone to study 15 probands from 11 families with this inherited disorder. Surprisingly, 7 of the probands from 4 families, of different ancestries, had a similar insertion in their LPL gene. In contrast to other human genetic disorders, where insertions are rare causes of mutation, this insertion accounts for a significant proportion of the alleles causing LPL deficiency. Detailed restriction mapping of the insertion revealed that it was unlikely to be a duplication of neighboring DNA and that it was not similar to the consensus sequence of human L1 repetitive elements. This suggest that there must be other mechanisms of insertional mutagenesis in human genetic disease besides transposition of mobile L1 repetitive elements.This publication has 24 references indexed in Scilit:
- Detection of specific sequences among DNA fragments separated by gel electrophoresisPublished by Elsevier ,2006
- Transcriptional activation of the lipoprotein lipase and apolipoprotein E genes accompanies differentiation in some human macrophage-like cell linesBiochemistry, 1988
- Insertional Mutagenesis of the Drosophila Genome with Single P ElementsScience, 1988
- Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in manNature, 1988
- Direct detection of more than 50% of the Duchenne muscular dystrophy mutations by field inversion gelsNature, 1987
- Preferential deletion of exons in Duchenne and Becker muscular dystrophiesNature, 1987
- HPRT: GENE STRUCTURE, EXPRESSION, AND MUTATIONAnnual Review of Genetics, 1985
- Selective Measurement of Two Lipase Activities in Postheparin Plasma from Normal Subjects and Patients with HyperlipoproteinemiaJournal of Clinical Investigation, 1974
- Tissue Lipoprotein Lipase in Normal Individuals and in Individuals with Exogenous Hypertriglyceridemia and the Relationship of this Enzyme to Assimilation of Fat *Journal of Clinical Investigation, 1967
- IDIOPATHIC HYPERLIPEMIA: METABOLIC STUDIES IN AN AFFECTED FAMILY*Journal of Clinical Investigation, 1960