Journal Article

A regulatory SNP of the <i>BICD1</i> gene contributes to telomere length variation in humans

Massimo Mangino, Scott Brouilette, Peter Braund, Nighat Tirmizi, Mariuca Vasa-Nicotera, John R. Thompson and Nilesh J. Samani

in Human Molecular Genetics

Volume 17, issue 16, pages 2518-2523
Published in print August 2008 | ISSN: 0964-6906
Published online May 2008 | e-ISSN: 1460-2083 | DOI:
A regulatory SNP of the BICD1 gene contributes to telomere length variation in humans

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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 × 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.

Journal Article.  3848 words.  Illustrated.

Subjects: Genetics and Genomics

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