An Aboriginal Australian Genome Project
Dr Ashley Farlow
Genome Biologist, National Centre for Indigenous Genomics, The Australian National University
Reconstruction of a human genome de novo from Australian Indigenous individuals reveals the amount of genetic variation that is not readily recovered using standard techniques. I will present a joint analysis of Illumina whole genome sequencing from 168 individuals and long-read de novo assemblies from 4 individuals for four remote Aboriginal communities. Consistent with their deep cultural and linguistic distinction, these communities display strong genetic population structure and a wealth of novel genetic variation.
I will focus on the surprising observation that these assemblies reveal a substantial amount of single nucleotide variation in regions of the reference genome not previously considered problematic when using standard approaches.
National Centre for Indigenous Genomics enabling the inclusion of Indigenous Australians in precision medicine
Dr Hardip Patel
Bioinformatics Lead, National Centre for Indigenous Genomics, The Australian National University
Large-scale projects that develop perpetual community resources, such as UK Biobank, 1000 Genome Project, and the Human PanGenome Reference, play an increasingly important role in biomedical research and precision medicine. The National Centre for Indigenous Genomics (NCIG) is establishing genomic reference resources and related biospecimens from Indigenous Australians. It is an example of a community resource built to enable broad-scale representation of ancestrally diverse populations to enable equitable benefits of genomics for all humans, irrespective of their ancestry. In the first phase, we have established deeply trusted relationships with four Indigenous communities; 684 individuals (10% of population) have donated their genomic data and samples into the growing NCIG collection. We have begun generating reference genomes leading to telomere-2-telomere assemblies. In addition, whole-genome sequence data from 160 individuals using ONT long reads and Illumina short reads has revealed distinct genetic diversity missing from global resources and specific to Indigenous communities. We have established first that the unique genetic diversity of Indigenous Australia will require modification to data analysis workflows to discover genetic variations accurately. Second, many more Indigenous communities would have to be included in genetic reference resources to comprehensively ascertain genetic diversity to benefit all Indigenous Australians. The next phase of NCIG, under Indigenous governance backed by federal statutory powers, will enable integration of these genomic resources into clinical practice in coming years.
Investigating the genetic basis of chronic kidney disease in the Tiwi Islands
Dr Simon Jiang
Nephrologist and Group Leader, College of Health and Medicine, The Australian National University
Indigenous Australian populations have the highest recorded rates of chronic kidney disease (CKD) worldwide. These rates of kidney disease are in excess of rates of diabetes and other cardiovascular ilness in these communities. It has been estimated that genetics accounts for 60% of the risk of CKD. We have established a national collaboration to sequence and define the genetic contribution to the high rates of CKD in Indigenous communities.
From this we have identified rare, potentially deleterious variants in CKD-relevant genes at high frequencies in patients from the Tiwi Islands including A20/TNFAIP3, AIRE, BLK, IRF5 as well variants in IRAK3, LYN, TRAF5 and RELB which are unique to the Tiwi. Variants in A20, LYN and AIRE were validated for altered function. Whilst the LYN variant had no impact, one variant in AIRE and two in A20 impaired IFN and NFkB expression respectively, highlighting the importance of understanding the unique pathophysiologic processes in Indigenous communities.