Ttn as a likely causal gene for QTL of alcohol preference on mouse chromosome 2

Lishi Wang,Robert W Williams,Weikuan Gu,Yan Jiao,Yue Huang,Dawei Li,Beth Bennett,Lindsay A Farrer,Joel Gelernter,Henry R Kranzler,Hongyu Zhao

doi:10.1186/1471-2105-15-s10-p12

Abstract

Background Many quantitative trait loci (QTL) influencing mouse model phenotypes for alcoholism have been mapped genetically. However, the gene(s) comprising the QTL (QTG) are largely unknown. In previous work, Bennett and colleagues created congenic strains carrying the DBA/2IBG (D2) region for alcohol preference (AP) on chromosome 2, on a C57BL/6IBG (B6) background [1]. Subsequently, interval specific congenic recombinant strains (ISCRS), in which the full D2 QTL region was broken into smaller, partially overlapping regions of introgression, were generated and tested. With information from two ISCRS, the QTL has been mapped onto mouse chromosome 2 (Chr2) in a region of 3.4Mb by using C57BL/6J (B6) x DBA/2J (D2) recombinant inbred (RI) strains as well as by using F2 populations. Several candidate genes, Gad1, Atp5g3, Atf2, Sp3 and Sp9, have been evaluated but none of them has been confirmed for a definitive role in the regulation of the QTL of AP on Chr2 [2,3].

Highlights

Many quantitative trait loci (QTL) influencing mouse model phenotypes for alcoholism have been mapped genetically
* Correspondence: wgu@uthsc.edu 1Department of Orthopaedic Surgery & BME - Campbell Clinic and Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USA Full list of author information is available at the end of the article recombinant strains (ISCRS); and 4) analysis of the association of candidate genes in the human population
Our data indicated that 1) the expression level of Ttn in the less alcohol preference (AP) congenic strains is significantly higher than that in by using C57BL/6J (B6); 2) the expression of a Ttn probe in the BXD recombinant inbred (RI) strains is negatively correlated to that of AP; 3) One SNP is up- and the other is downstream of Ttn

Summary

Introduction

Many quantitative trait loci (QTL) influencing mouse model phenotypes for alcoholism have been mapped genetically. * Correspondence: wgu@uthsc.edu 1Department of Orthopaedic Surgery & BME - Campbell Clinic and Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USA Full list of author information is available at the end of the article recombinant strains (ISCRS); and 4) analysis of the association of candidate genes in the human population.

Results

Conclusion