Imperial College London
Dr Alexessander da Silva Couto Alves

DrAlexessanderda Silva Couto Alves

Faculty of Medicine, School of Public Health

Honorary Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 3420a.couto-alves

 
 
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Location

 

150Variety Club WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{El-Sayed:2012:hmg/dds187,
author = {El-Sayed, Moustafa JS and Eleftherohorinou, H and de, Smith AJ and Andersson-Assarsson, JC and Alves, AC and Hadjigeorgiou, E and Walters, RG and Asher, JE and Bottolo, L and Buxton, JL and Sladek, R and Meyre, D and Dina, C and Visvikis-Siest, S and Jacobson, P and Sjostrom, L and Carlsson, LM and Walley, A and Falchi, M and Froguel, P and Blakemore, AI and Coin, LJ},
doi = {hmg/dds187},
journal = {Hum Mol Genet},
pages = {3727--3738},
title = {Novel association approach for variable number tandem repeats (VNTRs) identifies DOCK5 as a susceptibility gene for severe obesity},
url = {http://dx.doi.org/10.1093/hmg/dds187},
volume = {21},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Variable number tandem repeats (VNTRs) constitute a relatively under-examined class of genomic variants in the context of complex disease because of their sequence complexity and the challenges in assaying them. Recent large-scale genome-wide copy number variant mapping and association efforts have highlighted the need for improved methodology for association studies using these complex polymorphisms. Here we describe the in-depth investigation of a complex region on chromosome 8p21.2 encompassing the dedicator of cytokinesis 5 (DOCK5) gene. The region includes two VNTRs of complex sequence composition which flank a common 3975 bp deletion, all three of which were genotyped by polymerase chain reaction and fragment analysis in a total of 2744 subjects. We have developed a novel VNTR association method named VNTRtest, suitable for association analysis of multi-allelic loci with binary and quantitative outcomes, and have used this approach to show significant association of the DOCK5 VNTRs with childhood and adult severe obesity (P(empirical)= 8.9 x 10(-8) and P= 3.1 x 10(-3), respectively) which we estimate explains ~0.8% of the phenotypic variance. We also identified an independent association between the 3975 base pair (bp) deletion and obesity, explaining a further 0.46% of the variance (P(combined)= 1.6 x 10(-3)). Evidence for association between DOCK5 transcript levels and the 3975 bp deletion (P= 0.027) and both VNTRs (P(empirical)= 0.015) was also identified in adipose tissue from a Swedish family sample, providing support for a functional effect of the DOCK5 deletion and VNTRs. These findings highlight the potential role of DOCK5 in human obesity and illustrate a novel approach for analysis of the contribution of VNTRs to disease susceptibility through association studies.
AU  - El-Sayed,Moustafa JS
AU  - Eleftherohorinou,H
AU  - de,Smith AJ
AU  - Andersson-Assarsson,JC
AU  - Alves,AC
AU  - Hadjigeorgiou,E
AU  - Walters,RG
AU  - Asher,JE
AU  - Bottolo,L
AU  - Buxton,JL
AU  - Sladek,R
AU  - Meyre,D
AU  - Dina,C
AU  - Visvikis-Siest,S
AU  - Jacobson,P
AU  - Sjostrom,L
AU  - Carlsson,LM
AU  - Walley,A
AU  - Falchi,M
AU  - Froguel,P
AU  - Blakemore,AI
AU  - Coin,LJ
DO  - hmg/dds187
EP  - 3738
PY  - 2012///
SN  - 1460-2083
SP  - 3727
TI  - Novel association approach for variable number tandem repeats (VNTRs) identifies DOCK5 as a susceptibility gene for severe obesity
T2  - Hum Mol Genet
UR  - http://dx.doi.org/10.1093/hmg/dds187
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22595969
VL  - 21
ER  -
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