Savage Sharon A, Stewart Brian J, Eckert Andrew, Kiley Maureen, Liao Jason S, Chanock Stephen J
Section on Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA.
Hum Mutat. 2005 Oct;26(4):343-50. doi: 10.1002/humu.20226.
To maintain chromosomal integrity and to protect the ends of chromosomes against recognition as damaged DNA, end-to-end fusion, or recombination, a coordinated set of genes is required to stabilize the telomere. We surveyed common genetic variation in seven genes that are vital to telomere stability (TERT, POT1, TNKS, TERF1, TINF2, TERF2, and TERF2IP) and validated single nucleotide polymorphisms (SNPs) in four different ethnic groups (n=118 total). Overall, our data show limited degrees of nucleotide diversity in comparison with data from other gene families. We observed that these genes are highly conserved in sequence between species, and that for nearly all of the coding SNPs the most common allele is ancestral (i.e., it is observed in primate sequences). Our findings support the hypothesis that genetic variation in a pathway that is critical for telomere stability may be under constraint. These data establish a foundation for further investigation of these genes in population-genetics, evolution, and disease-association studies.
为维持染色体完整性，并保护染色体末端不被识别为受损DNA、不发生端对端融合或重组，需要一组协调的基因来稳定端粒。我们调查了对端粒稳定性至关重要的七个基因（TERT、POT1、TNKS、TERF1、TINF2、TERF2和TERF2IP）中的常见遗传变异，并在四个不同种族群体（共118人）中验证了单核苷酸多态性（SNP）。总体而言，与其他基因家族的数据相比，我们的数据显示核苷酸多样性程度有限。我们观察到这些基因在物种间序列高度保守，并且几乎所有编码SNP的最常见等位基因都是祖先型的（即在灵长类序列中观察到）。我们的研究结果支持这样一种假说，即对端粒稳定性至关重要的通路中的遗传变异可能受到限制。这些数据为在群体遗传学、进化和疾病关联研究中进一步研究这些基因奠定了基础。
