Over the last 10 years, several hundred individuals from four remote communities in north and central Australia have consented to their blood or saliva samples being DNA sequenced for the purpose of genomic research.
Together with the National Centre for Indigenous Genomics (NCIG), we present a joint analysis of Illumina whole genome sequencing from 168 individuals and long-read de novo assemblies from 4 individuals. Consistent with their deep cultural and linguistic distinction, these communities display strong genetic population structure and a wealth of novel genetic variation.
Our ability to reconstruct a genome de novo from each community reveals the amount of genetic variation that is not readily recovered using short reads and the reference genome alone. As one might expect, assembly allows the identification of more than double the number of structural variants within an individual's genome compared to that recovered using typical short-read structural variant callers.
Perhaps surprisingly, assembly also reveals a substantial amount of single nucleotide variation in regions of the reference genome not previously considered problematic using standard approaches. We discuss the population and genomic causes of this disparity and the possible consequences when Indigenous ancestry is not taken into account during typical research and clinical analysis.