Genetic variation, nucleotide diversity, and linkage disequilibrium in seven telomere stability genes suggest that these genes may be under constraint

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Conserved Sequence
  • Ethnicity / genetics
  • Genetic Variation*
  • Haplotypes
  • Heterozygote
  • Humans
  • Linkage Disequilibrium / genetics*
  • Mice
  • Pan troglodytes / genetics
  • Polymorphism, Single Nucleotide*
  • Pongo pygmaeus / genetics
  • Regulatory Elements, Transcriptional
  • Sequence Analysis, DNA
  • Species Specificity
  • Telomere / genetics
  • Telomere / metabolism
  • Telomere-Binding Proteins / genetics*
  • Telomere-Binding Proteins / metabolism


  • Telomere-Binding Proteins

Associated data

  • OMIM/127550
  • OMIM/187270
  • OMIM/600951
  • OMIM/602027
  • OMIM/602322
  • OMIM/606505