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Sci Rep. 2017 Nov 21;7(1):15888. doi: 10.1038/s41598-017-15752-4.

Whole Exome Sequencing reveals new candidate genes in host genomic susceptibility to Respiratory Syncytial Virus Disease.

Author information

1
Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela(USC), Galicia, Spain. antonio.salas@usc.es.
2
GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago de Compostela (SERGAS), Galicia, Spain. antonio.salas@usc.es.
3
Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain. antonio.salas@usc.es.
4
GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain. antonio.salas@usc.es.
5
Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela(USC), Galicia, Spain.
6
GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago de Compostela (SERGAS), Galicia, Spain.
7
Translational Pediatrics and Infectious Diseases, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
8
GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago, Galicia, Spain.

Abstract

Respiratory syncytial virus (RSV) is an important cause of serious lower respiratory tract disease in infants. Several studies have shown evidence pointing to the genome of the host as an important factor determining susceptibility to respiratory disease caused by RSV. We sequenced the complete exomes of 54 patients infected by RSV that needed hospitalization due to development of severe bronchiolitis. The Iberian sample (IBS) from The 1000 Genomes Project (1000G) was used as control group; all the association results were pseudo-replicated using other 1000G-European controls and Spanish controls. The study points to SNP rs199665292 in the olfactory receptor (OR) gene OR13C5 as the best candidate variant (P-value = 1.16 × 10-12; OR = 5.56). Genetic variants at HLA genes (HLA-DQA1, HLA-DPB1), and in the mucin 4 gene (MUC4) also emerge as susceptibility candidates. By collapsing rare variants in genes and weighing by pathogenicity, we obtained confirmatory signals of association in the OR gene OR8U1/OR8U8, the taste receptor TAS2R19, and another mucin gene (MUC6). Overall, we identified new predisposition variants and genes related to RSV infection. Of special interest is the association of RSV to olfactory and taste receptors; this finding is in line with recent evidence pointing to their role in viral infectious diseases.

PMID:
29162850
PMCID:
PMC5698448
DOI:
10.1038/s41598-017-15752-4
[Indexed for MEDLINE]
Free PMC Article

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