Mapping of a major locus that determines telomere length in humans
Mapping of a major locus that determines telomere length in humans
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DOI：
10.1086/426734
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发表时间：
2005-01-01
影响因子：
9.8
通讯作者：
Samani, NJ
中科院分区：
文献类型：
--
作者：
Vasa-Nicotera, M;Brouilette, S;Samani, NJ
端粒长度是染色体正常功能和衰老的关键因素。人类的平均端粒长度显示出相当大的个体间差异和强烈的遗传决定。为了了解是否可以绘制影响人类端粒长度的基因座（或基因座），我们对383名成年受试者（包括258个同胞对）进行了平均白细胞端粒限制性片段（TRF）长度的定量性状连锁分析。平均（+/- SE）TRF的遗传率为81.9% +/-11.8%。平均TRF长度与12号染色体上的一个位点存在显著连锁（LOD评分3.20），这解释了平均TRF长度总体变异的49%。我们提出了一个强有力的候选基因在该地区，DNA解旋酶DDX 11的初步分析。总之，我们报告的第一个基因座，决定平均端粒长度在人类的映射。鉴定所涉及的基因并阐明其作用机制可能对我们理解染色体组装、端粒生物学和年龄相关疾病的易感性具有重要意义。
Telomere length is a crucial factor for both normal chromosomal function and senescence. Mean telomere length in humans shows considerable interindividual variation and strong genetic determination. To see if a locus ( or loci) affecting telomere length in humans could be mapped, we performed a quantitative-trait linkage analysis of mean leukocyte telomere-restriction-fragment (TRF) lengths, measured by Southern blotting, in 383 adult subjects comprising 258 sib pairs. Heritability of mean (+/- SE) TRF was 81.9% +/- 11.8%. There was significant linkage (LOD score 3.20) of mean TRF length to a locus on chromosome 12, which explained 49% of the overall variability in mean TRF length. We present preliminary analysis of a strong candidate gene in the region, the DNA helicase DDX11. In conclusion, we report mapping of the first locus that determines mean telomere length in humans. Identification of the gene involved and elucidation of its mechanism of action could have important implications for our understanding of chromosomal assembly, telomere biology, and susceptibility to age-related diseases.