Skip Navigation


Human Molecular Genetics Advance Access originally published online on May 16, 2008
Human Molecular Genetics 2008 17(16):2518-2523; doi:10.1093/hmg/ddn152
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
17/16/2518    most recent
ddn152v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Mangino, M.
Right arrow Articles by Samani, N. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mangino, M.
Right arrow Articles by Samani, N. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A regulatory SNP of the BICD1 gene contributes to telomere length variation in humans

Massimo Mangino1, Scott Brouilette1, Peter Braund1, Nighat Tirmizi1, Mariuca Vasa-Nicotera1, John R. Thompson2 and Nilesh J. Samani1,*

1 Department of Cardiovascular Sciences 2 Department of Health Sciences, University of Leicester, Leicester, UK

* To whom correspondence should be addressed at: Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK. Tel: +44 1162563021; Fax: +44 1162875792. Email: njs{at}le.ac.uk

Received March 13, 2008; Revised April 27, 2008; Accepted May 14, 2008

Telomeres are repetitive sequences of variable length at the ends of chromosomes involved in maintaining their integrity. Telomere dysfunction is associated with increased risk of cancer and other age-related diseases. Telomere length is an important determinant of telomere function and has a strong genetic basis. We previously carried out a genome-wide linkage analysis of mean leukocyte telomere length, and identified a 12 cM quantitative-trait locus affecting telomere length on human chromosome 12. In the present study we confirmed linkage to this locus in an extended sample (380 families, 520 sib-pairs, maximum LOD score 4.3). Fine-mapping identified a 51 kb region of association within intron 1 of the Bicaudal-D homolog 1 (BICD1, MIM 602204 [OMIM] ) gene. The strongest association (P = 1.9 x 10–5) was with SNP rs2630578 where the minor allele C (frequency 0.21) was associated with telomeres that were shorter by 604 (±204) base pairs, equivalent to ~15–20 years of age-related attrition in telomere length. Subjects carrying the C allele for rs2630778 had 44% lower BICD1 mRNA levels in their leukocytes compared with GG homozygotes (P = 0.004). BICD1 is involved in Golgi-to-endoplasmic reticulum vacuolar transport. Previous studies have implicated vacuolar genes in telomere length homeostasis in yeast. Our study indicates that BICD1 plays a similar role in humans.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.