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© Research
Publication : HLA

Characterising the genetic basis of immune response variation to identify causal mechanisms underlying disease susceptibility.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in HLA - 01 Sep 2019

Rotival M,

Link to Pubmed [PMID] – 31115186

Link to DOI [DOI] – 10.1111/tan.13598

HLA 2019 09; 94(3): 275-284

Over the last 10 years, genome-wide association studies (GWAS) have identified hundreds of susceptibility loci for autoimmune diseases. However, despite increasing power for the detection of both common and rare coding variants affecting disease susceptibility, a large fraction of disease heritability has remained unexplained. In addition, a majority of the identified loci are located in noncoding regions, and translation of disease-associated loci into new biological insights on the etiology of immune disorders has been lagging. This highlights the need for a better understanding of noncoding variation and new strategies to identify causal genes at disease loci. In this review, I will first detail the molecular basis of gene expression and review the various mechanisms that contribute to alter gene activity at the transcriptional and post-transcriptional level. I will then review the findings from 10 years of functional genomics studies regarding the genetics on gene expression, in particular in the context of infection. Finally, I will discuss the extent to which genetic variants that modulate gene expression at transcriptional and post-transcriptional level contribute to disease susceptibility and present strategies to leverage this information for the identification of causal mechanisms at disease loci in the era of whole genome sequencing.

https://pubmed.ncbi.nlm.nih.gov/31115186