| Title |
Substantial linkage disequilibrium across the insulin-degrading enzyme locus but no association with late-onset Alzheimer's disease
|
|---|---|
| Published in |
Human Genetics, November 2001
|
| DOI | 10.1007/s00439-001-0614-1 |
| Pubmed ID | |
| Authors |
Richard Abraham, Amanda Myers, Fabienne Wavrant-DeVrieze, Marian L. Hamshere, Hollie V. Thomas, Helen Marshall, Danielle Compton, Gillian Spurlock, Dragana Turic, Bastiaan Hoogendoorn, Jennifer M. Kwon, Ronald C. Petersen, Eric Tangalos, Joanne Norton, John C. Morris, Roger Bullock, Danae Liolitsa, Simon Lovestone, John Hardy, Alison Goate, Michael O'Donovan, Julie Williams, Michael J. Owen, Lesley Jones |
| Abstract |
Insulin-degrading enzyme (IDE; insulysin; EC 3.4.24.56) is a 110-kDa neutral metallopeptidase that can degrade a number of peptides including beta-amyloid. The gene encoding IDE is located on chromosome 10 close to a region of linkage for late-onset Alzheimer's disease (LOAD) and thus is a functional and positional candidate for this disorder. We analysed all of the coding exons, untranslated regions and 1000 bp of 5'-flanking sequence of IDE by using denaturing high-performance liquid chromatography and sequencing. We detected eight single nucleotide polymorphisms (SNPs), three in the 5' flanking sequence and five in the coding sequence, of which three were found at lower than 5% frequency. None of them changed the amino acid sequence. We genotyped the five SNPs with allele frequencies of more than 5% in 133 Caucasian LOAD cases and 135 controls collected in the UK and 95 cases and 117 controls collected at the Mayo Clinic, Rochester, USA. Two of the SNPs were analysed in a further independent case-control sample (Washington University, St. Louis: 86 cases, 94 controls). No significant association was found with any individual SNP in any of the samples or with any haplotypes. Analysis of the marker D10S583, which maps 36 kb upstream of IDE, also failed to show association in 134 cases and 111 matched controls from the UK ( P=0.63). Strong linkage disequilibrium was detected between the five SNPs that spanned the whole of the 120-kb genomic region of IDE and one major and a number of minor haplotypes were detected in the populations studied. We conclude that IDE does not make a substantial contribution to the aetiology of LOAD and therefore cannot account for the linkage between LOAD and 10q. |
Mendeley readers
The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 2% |
| United States | 1 | 2% |
| Unknown | 43 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 20% |
| Professor > Associate Professor | 7 | 16% |
| Professor | 5 | 11% |
| Other | 5 | 11% |
| Student > Ph. D. Student | 5 | 11% |
| Other | 6 | 13% |
| Unknown | 8 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 24% |
| Agricultural and Biological Sciences | 10 | 22% |
| Neuroscience | 8 | 18% |
| Biochemistry, Genetics and Molecular Biology | 3 | 7% |
| Psychology | 3 | 7% |
| Other | 3 | 7% |
| Unknown | 7 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 June 2015.
All research outputs
#7,487,068
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Outputs from Human Genetics
#937
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#14,485
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Outputs of similar age from Human Genetics
#9
of 24 outputs
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