This article is part of the supplement: UT-ORNL-KBRIN Bioinformatics Summit 2008 .

Poster presentation

Bioinformatics analysis of immune response to group A streptococcal sepsis integrating quantitative trait loci mapping with genome-wide expression studies

Nourtan Abdeltawab^1,5, Rita Kansal¹, Sarah Rowe⁵, Lidia Gardner¹, Charity Brannen¹, Mohammed Nooh^1,2,5, Santhosh Mukundan¹, Hossam Abdelsamed^1,2,5, Ramy Attia^1,5, William Taylor⁴, Lu Lu³, Robert Williams³ and Malak Kotb^1,2,5

¹  Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA

²  Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA

³  Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA

⁴  Molecular Resource Center, University of Tennessee Health Science Center, Memphis, TN 38163, USA

⁵  Veterans Affairs Medical Center, Memphis, TN 38104, USA

author email corresponding author email

from UT-ORNL-KBRIN Bioinformatics Summit 2008
Cadiz, KY, USA. 28–30 March 2008

BMC Bioinformatics 2008, 9(Suppl 7):P6doi:10.1186/1471-2105-9-S7-P6

Published:	8 July 2008

First paragraph (this article has no abstract)

Individuals infected with genetically identical group A streptococcal (GAS) strains develop starkly different disease progression and outcome [1]. We reported that HLA class II allelic variation contributes to differences in systemic disease severity by modulating host responses to streptococcal superantigens [2]. Inasmuch as the bacteria produce additional virulence factors, we sought to identify additional host gene networks modulating GAS sepsis. Accordingly, we used two parallel approaches to define these gene networks, quantitative trait loci (QTL) mapping and genome-wide transcriptome analyses. To map QTLs modulating response to severe GAS sepsis, we used advanced recombinant inbred (ARI) strains, which are genetically diverse strains that have common ancestral parents [3]. We chose to use BXD strains of ARI mice, as parental strains C57Bl/6J (B6) and DBA/2J (D2) show differential response to GAS sepsis and BXD strains are heavily genotyped at 13377 SNPs and microsatellite markers. BXD strains, derived from B6 and D2 parental strains, are homozygous inbred lines, each of which is genetically distinct. Using 30 different BXD strains (n = 5–26 mice per strain), we identified significant QTLs on chromosome 2 that strongly modulate disease severity [4]. To narrow down these mapped QTLs, we applied bioinformatics tools including: linkage, interval specific haplotype analyses, and gene ontology and we identified multiple candidate gene networks modulating immune response to sepsis.