Research Focus: Unravelling the First Bruneian Genomes 5 Advancement in next generation sequencing (NGS) and computational technologies over the last decade has allowed sequencing of the entire human genome to be routinely performed for various biomedical and clinical applications. The underlying genetic causes of many human phenotypes and diseases, such as cancer, have also come to light with the identification of variants (e.g. single nucleotide variant (SNV) and insertion/deletion (indel)) derived from these data. Indeed, prescription of pharmacogenomic treatments incorporating personalised genetic data is now in practice for a number of genetic diseases. However, realisation of true precision medicine can only be achieved when genetic variants from both healthy and diseased groups can be analysed and compared to ascertain the causative aberrant genetic elements. In Brunei, little is known about the genetic variation within the local population groups. To date, although genetic testing for some inherited diseases and certain cancer types have been made available in the country, none of the variants identified has been deposited in NCBI’s dbSNP database, and in fact, less than 10 human DNA sequences can be found in the NCBI’s GenBank database. The much needed effort and challenge to quickly fill in these gaps has been taken up by two final year biomedical science undergraduate students, Mirza Azmi and Nabil Abdul Kadir, at our Institute. Both are under the supervision of Dr Lu Zen Huat and the project is in collaboration with Dr Hj Abdul Ghani Hj Naim of Institute of Applied Data Analytics. The whole genome of two Dusun individuals from Brunei were recently sequenced, using the NGS method, as a small part of The Simons Foundation’s Human Diversity Project. While focusing on the evolutionary genetics, detailed analysis was not done for any of the 300+ individual genomes. Mirza and Nabil were therefore tasked with analysing the raw sequencing data and identifying all the genetic variants in the two individuals. After overcoming the steep learning curve in genomics, bioinformatics, data analytics and Linux computing, they have to plough through NGS data exceeding 150GB using some state-of-the-art bioinformatics tools running on the high performance Linux server at the Information Communication Technology Centre (ICTC). In brief, raw sequencing reads derived from the genome of the two individuals were first mapped (i.e. aligned) against different versions of the latest human reference genome before all the potential variants were discovered and quality-filtered. Each of the two individuals was found to harbour approximately 4.1 million genetic variants. Preliminary analysis shows that more than 100,000 of the variants have not been reported in the NCBI’s dbSNP database. Mirza and Nabil next attempted to look at the molecular and inferred clinical impacts of these variants. They were able to identify SNVs in genes associated with drug response and genetic diseases. For instance, a SNV falling on the miRNA regulating the Brca2 gene expression was identified in the female Dusun and this SNV has been predicted to increase the risk of breast cancer. Findings from the current works will be presented during their final year project presentation. Although the work thus far have been limited to only two Bruneian individuals, this whole genome variant discovery project is, to our best knowledge, first of its kind in the Sultanate. Future research in population genetics and genomics will lead to better understanding of diseases and more accurate prediction of drug responses within the different Bruneian population groups. Ultimately, the practice of genomic medicine is expected to greatly improve the healthcare in the country. This is an important milestone in the progress of genomic medicine at not only the university, but also the Sultanate. One small step for human genomics, one giant leap for personalized medicine in Brunei
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