The use of genome wide association methods to investigate pathogenicity, population structure and serovar in Haemophilus parasuis

BMC Genomics

Research Article

Susanna M Williamson¹  Virginia Aragon²  Albert Bensaid²  Jukka Corander³  Paul R Langford⁴  Roy R Chaudhuri⁵  Lucy A Weinert⁶  Sarah E Peters⁶  Duncan J Maskell⁶  Shi-Lu Luan⁶  Alexander W Tucker⁶  Kate J Howell⁶  Brendan W Wren⁷  Øystein Angen⁸  Matthew T G Holden⁹  Andrew N Rycroft^1,10  David Harris^1,11  Julian Parkhill^1,11 

[1] Animal Health and Veterinary Laboratories Agency (AHVLA), IP33 2RX, Rougham Hill, Bury St Edmunds, Suffolk, UK;Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, and Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Barcelona, Spain;Department of Mathematics and Statistics, University of Helsinki, 00100, Helsinki, Finland;Department of Medicine, Section of Paediatrics, Imperial College London, St. Mary’s Campus,, W2 1PG, London, UK;Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, S10 2TN, Western Bank, Sheffield, UK;Department of Veterinary Medicine, University of Cambridge, Madingley Road, CB3 0ES, Cambridge, UK;Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, WC1E 7HT, London, UK;Norwegian Veterinary Institute, N-0106, Oslo, Norway;School of Medicine, University of St. Andrews, KY16 9TF, St Andrews, UK;The Royal Veterinary College, Hawkshead Campus, AL9 7TA, HatfieldHertfordshire, UK;The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, Cambridge, UK;

关键词: Genome wide association study;    Pan-genome;    Recombination;    DAPC;    Virulence factors;    Population structure;    Haemophilus parasuis;   

DOI  :  10.1186/1471-2164-15-1179

 received in 2014-06-30, accepted in 2014-12-12,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundHaemophilus parasuis is the etiologic agent of Glässer’s disease in pigs and causes devastating losses to the farming industry. Whilst some hyper-virulent isolates have been described, the relationship between genetics and disease outcome has been only partially established. In particular, there is weak correlation between serovar and disease phenotype. We sequenced the genomes of 212 isolates of H. parasuis and have used this to describe the pan-genome and to correlate this with clinical and carrier status, as well as with serotype.ResultsRecombination and population structure analyses identified five groups with very high rates of recombination, separated into two clades of H. parasuis with no signs of recombination between them. We used genome-wide association methods including discriminant analysis of principal components (DAPC) and generalised linear modelling (glm) to look for genetic determinants of this population partition, serovar and pathogenicity. We were able to identify genes from the accessory genome that were significantly associated with phenotypes such as potential serovar specific genes including capsule genes, and 48 putative virulence factors that were significantly different between the clinical and non-clinical isolates. We also show that the presence of many previously suggested virulence factors is not an appropriate marker of virulence.ConclusionsThese genes will inform the generation of new molecular diagnostics and vaccines, and refinement of existing typing schemes and show the importance of the accessory genome of a diverse species when investigating the relationship between genotypes and phenotypes.

【 授权许可】

CC BY   
© Howell et al.; licensee BioMed Central. 2014