SysGen seminar – Lesley Gray – 15th July, 2016

darwintree_blue_tips_sysgen2

Genetic determinants of rheumatic heart disease in Indigenous Australians

Dr Lesley Gray
Centre for Systems Genomics

Friday 15th July
11:00am-12:00pm
ESJ King Theatre, Medical Building, The University of Melbourne

Rheumatic Heart Disease (RHD) is the most common cause of cardiac death in people under 40 years old. Much is unknown about the pathogenesis of RHD, however it is generally accepted that untreated recurrent throat infections caused by group A streptococcus (GAS) can progress into rheumatic fever causing exaggerated immune responses that in an estimated 60% of cases results in RHD. While aspects of RHD pathogenesis have been attributed to poor hygiene conditions and reduced medical access in developing areas, recent studies suggest that the contribution of genetics may be as high as 60%. In Australia, the incidence of RHD in the indigenous population is more than 2% and the mean age of onset is almost half that seen in the non-indigenous population. To identify the genetic factors underlying susceptibility to RHD we conducted the first large-scale genome wide association study for rheumatic heart disease in indigenous Australians. We genotyped 1,340 individuals using the HumanCoreExome array and further imputed SNP variation genome-wide. Using linear mixed models, we performed genome-wide scans for variants associated with RHD case/control status as well as RHD sub-phenotypes defined by echocardiograph. We identified associations within the well-known Human Leukocyte Antigen (HLA) locus suggesting a shared genetic component to other known autoimmune diseases. Targeted imputation and sequencing of HLA was undertaken to fine-map these associations to key variants within this important immunoregulatory gene family. These results provide exciting insight into the factors causing increased susceptibility to RHD in high-risk indigenous populations and offer new avenues for exploration of diagnosis and treatment options that can be applied to RHD research globally.

Bio

Lesley completed a Bachelor of Biological Sciences at La Trobe University with honours in the field of quantitative genetics. She completed a PhD at the Department of Primary Industries researching the genetics of milk production and fertility for selective breeding in dairy cattle, lead by Prof. Benjamin Cocks and Assoc. Prof. Ben Hayes. As part of the Inouye Lab she now continues using the genome-wide approach and works towards identifying the genetic factors contributing to rheumatic heart disease in Indigenous Australians and improving genotype imputation. She has undertaken a broad range of roles in science including laboratory technician, lecturer, post-doctoral researcher building bacterial gene networks with the Holt laboratory, and also reviewing research outcomes for the DSDBI with the Small Technologies Cluster (STC). During her downtime she still pursues important scientific research genotyping her crossbreed dog, Belle, and works towards improving her performance in Melbourne fun runs with the Monash University running club.

Enquiries: Andrew Siebel (asiebel@unimelb.edu.au)