Changes in primary DNA sequence complexity influence the phenotypic consequences of mutations in human gene regulatory regions

R transversions was also apparent for transitions. These findings suggest that the maintenance of a defined level of DNA sequence complexity, or at least the avoidance of an increase in sequence complexity, is a critical prerequisite for the function of gene regulatory regions. -->
ISSN: 0340-6717
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c62382833239101e4d3f5dd4c3c80e0
https://pubmed.ncbi.nlm.nih.gov/11129336
Rights: CLOSED
Přírůstkové číslo: edsair.doi.dedup.....1c62382833239101e4d3f5dd4c3c80e0
Autor: Peter D. Stenson, David Neil Cooper, Nadia Chuzhanova, Bent N. Johansen, Edward V. Ball, Michael Krawczak
Rok vydání: 2000
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Zdroj: Scopus-Elsevier
ISSN: 0340-6717
Popis: No general rules have been proposed to account for the functional consequences of gene regulatory mutations. In a first attempt to establish the nature of such rules, an analysis was performed of the DNA sequence context of 153 different single base-pair substitutions in the regulatory regions of 65 different human genes underlying inherited disease. Use of a recently proposed measure of DNA sequence complexity (taking into account the level of structural repetitiveness of a DNA sequence, rather than simply the oligonucleotide composition) has served to demonstrate that the concomitant change in local DNA sequence complexity surrounding a substituted nucleotide is related to the likelihood of a regulatory mutation coming to clinical attention. Mutations that led to an increase in complexity exhibited higher odds ratios in favour of pathological consequences than mutations that led to a decrease or left complexity unchanged. This relationship, however, was discernible only for pyrimidine-to-purine transversions. Odds ratios for other types of substitution were not found to be significantly associated with local changes in sequence complexity, even though a trend similar to that observed for Y-->R transversions was also apparent for transitions. These findings suggest that the maintenance of a defined level of DNA sequence complexity, or at least the avoidance of an increase in sequence complexity, is a critical prerequisite for the function of gene regulatory regions.
Databáze: OpenAIRE
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