Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/16621
Title: A regulatory SNP of the BICD1 gene contributes to telomere length variation in humans.
Authors: Mangino, M
Brouilette, S
Braund, P
Tirmizi, N
Vasa-Nicotera, M
Thompson, JR
Samani, NJ
First Published: 15-Aug-2008
Citation: HUM MOL GENET, 2008, 17 (16), pp. 2518-2523
Abstract: 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) 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 approximately 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.
DOI Link: 10.1093/hmg/ddn152
eISSN: 1460-2083
Links: http://hdl.handle.net/2381/16621
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Health Sciences

Files in This Item:
There are no files associated with this item.


Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.