Project 1. Genotype-Phenotype Association in HLA Genes and AIDS: Progression Markers and Pharmacogenetics. (BB1, XB5, IO1, SI4)
Description and objectives:
Different histocompatibility antigens (HLA) have been implicated as prognosis markers of the evolution of HIV-1 disease and predictors of adverse events of antiretroviral therapy. It is yet unknown the prevalence of allele HLA-B * 5701 related to cases of abacavir hypersensitivity [a nucleoside analog reverse transcriptase inhibitor (NRTI)] on population infected with human immunodeficiency virus 1 (HIV-1), in Spain. The ultimate goal of this study is to quantify the prevalence of these haplotypes in a group of HIV-1 patients and assess their application in clinical usage. As specific objectives, include:
1. Molecular study of markers HLA B * 35, HLA-Cw * 04, HLA B * 27, HLA-B * 57, CCR2, CCR5, CX3CR1, and SDF1 and prognosis of the disease.
2. Correlation analysis of the of HLA B * 5701, Hsp70-Hom, and development of hypersensitivity to abacavir. Study of modification, appearance and/or severity of clinical aspects.
3. Identification of new alleles in genes HLA A, HLA-B, HLA C to determine the specific and characteristic haplotype of the Galician population.
To develop this project, in collaboration with Hospital Complex of Vigo (CHUVI), it has been contracted a PhD student, highlighting the experience in biostatistics, in the areas of Survival Analysis, Epidemiology, Neurology, oncology, and bioinformatics. The work in progress includes:
• Data Analysis (type of variables collected, number of cases, time of patient monitoring ,...) for the study of genotype-phenotype association.
• Possibilities of statistical analysis, and inclusion of new variables.
• Throughput, data collection and case refinement.
• Analysis of the database for the storage of genotypes and phenotypes
• Web server for remote execution of methods and algorithms developed during the project.
Group SI4 supports the implementation of associated software tools:
• experimental database for the storage of genotypes and phenotypes
• web server for remote execution of methods and algorithms developed during the project.
Collaboration between groups XB5 and SI4 has produceds the recent publication of the implementation of a web server capable of performing conversions between different formats of multiple sequence alignment.
[ALTER: program-oriented format conversion of DNA and protein alignments. Nucleic Acids Research. 38 (Web Server issue): W14-W18. (Doi:10.1093/nar/gkq321)]
ALTER’s front-end and its API are freely available at http://sing.ei.uvigo.es/ALTER/ and http://sing.ei.uvigo.es/ALTER/api/, respectively.