Evolution of a VNTR located within the promoter region of the thiopurine methyltransferase gene: inferences from population and sequence data View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-08

AUTHORS

Sandra Alves, António Amorim, Maria Prata

ABSTRACT

The promoter region of the human thiopurine methyltransferase (TPMT) gene contains a variable number of tandem repeats (VNTR) with three kind of motifs (A, B, and C) differing by the length of the unit core and nucleotide sequence. We have studied the structural variation within the VNTR alleles in two human populations and in samples from gorillas and chimpanzees. In humans, no intermingling of motifs was detected within the VNTR, and the sequences of the three core motifs remained remarkably unchanged, differences between alleles corresponding essentially to variations in the number of A and B repeats. The variation pattern in humans is consistent with an interpretation in which two contiguous genetic units (repeats A and B) behave evolutionarily according to the stepwise mutation model, as inferred from the population distribution profiles and from the molecular phylogenetic relationships among the VNTR alleles. However, the observation of a strong negative correlation between the numbers of A and B repeats also suggests that the regularity and/or independence of the mutational process has been disrupted to some extent by interactions between the A and B stretches. Selective pressure (the VNTR plays some role, although minor, in the TPMT function) or biased mutation are possible explanations. In gorillas and chimpanzees, several A-, B-, or C-like motifs were detected, but their arrangement within the VNTR alleles did not followed the regular pattern registered in humans and, particularly for the B-like motifs, a considerable sequence hypervariability was registered. Furthermore, the structural differences among non-human alleles were sufficiently numerous to render more plausible the assumption of the infinite allele model. More... »

PAGES

172-178

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00439-002-0784-5

DOI

http://dx.doi.org/10.1007/s00439-002-0784-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017007106

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12189491


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