Scientific article

Conserved noncoding sequences are selectively constrained and not mutation cold spots

Published inNature genetics, vol. 38, no. 2, p. 223-227
Publication date2006

Noncoding genetic variants are likely to influence human biology and disease, but recognizing functional noncoding variants is difficult. Approximately 3% of noncoding sequence is conserved among distantly related mammals, suggesting that these evolutionarily conserved noncoding regions (CNCs) are selectively constrained and contain functional variation. However, CNCs could also merely represent regions with lower local mutation rates. Here we address this issue and show that CNCs are selectively constrained in humans by analyzing HapMap genotype data. Specifically, new (derived) alleles of SNPs within CNCs are rarer than new alleles in nonconserved regions (P = 3 x 10(-18)), indicating that evolutionary pressure has suppressed CNC-derived allele frequencies. Intronic CNCs and CNCs near genes show greater allele frequency shifts, with magnitudes comparable to those for missense variants. Thus, conserved noncoding variants are more likely to be functional. Allele frequency distributions highlight selectively constrained genomic regions that should be intensively surveyed for functionally important variation.

  • Conserved Sequence/ genetics
  • Gene Frequency/genetics
  • Humans
  • Mutation/ genetics
  • Polymorphism, Single Nucleotide/genetics
  • Population Groups/genetics
  • Selection, Genetic
Citation (ISO format)
DRAKE, J. A. et al. Conserved noncoding sequences are selectively constrained and not mutation cold spots. In: Nature genetics, 2006, vol. 38, n° 2, p. 223–227. doi: 10.1038/ng1710
Main files (1)
ISSN of the journal1061-4036

Technical informations

Creation07/12/2010 11:57:45 AM
First validation07/12/2010 11:57:45 AM
Update time03/14/2023 3:50:49 PM
Status update03/14/2023 3:50:49 PM
Last indexation02/12/2024 6:50:47 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack