Comment on: Marchand and Polychronakos (2007) Evaluation of Polymorphic Splicing in the Mechanism of the Association of the Insulin Gene with Diabetes: Diabetes 56:709–713
- Santiago Rodriguez1,
- Tom R. Gaunt1,
- Igoř Vorechovský2,
- Jana Kralovičová2,
- Peter J. Wood2 and
- Ian N.M. Day1
- 1Bristol Genetic Epidemiology Laboratories (BGEL) and Medical Research Council Centre for Causal Analyses in Translational Epidemiology (CAiTE), Department of Social Medicine, University of Bristol, Bristol, U.K
- 2Human Genetics Division, University of Southampton School of Medicine, Southampton, U.K
- Address correspondence to Ian N.M. Day, Bristol Genetic Epidemiology Laboratories and the Medical Research Council Centre for Causal Analyses in Transitional Epidemiology, Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS82PR, U.K. E-mail: ian.day{at}bristol.ac.uk
This letter concerns quantitative modeling of allelic insulin gene splicing, transcription, and translation in complex traits. Marchand and Polychronakos (1) report an ex vivo study of allelic insulin gene pre-mRNA splicing in follow up to our demonstration (2) of the in silico and in vitro of effects of the −23HphI (IVSI-6A/T) polymorphism on 5′-noncoding intron I retention. This retention occurs in insulin mRNA, and there are additional consequential effects on translation from which we proposed a new category of quantitative trait loci dubbed STEPs (splice translational efficiency polymorphisms) (3). Marchand and Polychronakos confirmed the existence of message with intron I retention in human fetal pancreata, and they also confirmed …
