Long-read sequencing of neuropsychiatric disorder risk gene isoforms in human brain

Ricardo De Paoli-Iseppi

Ricardo De Paoli-Iseppi, The University of Melbourne


Neuropsychiatric disorders have a strong genetic component and hundreds of risk genes have been identified. How these genes contribute to disease risk is not well understood. Nanopore amplicon sequencing was used to examine the entire coding regions of two high-confidence risk genes in seven regions of post-mortem human brain from five control individuals. Pilot sequencing also identified 78 novel exons in 13 risk genes. Three novel isoforms were shown to contribute to over 25% of MAPT expression. Isoform abundance differences between cerebellum and cortical regions were also identified. Our study demonstrates the power of nanopore sequencing to characterise full-length isoform diversity in human brain.


Ricardo is a Postdoctoral Researcher with the Clark Lab at the University of Melbourne. Ricardo completed his PhD in 2019 at the University of Tasmania where he used short-read sequencing technologies to identify a biomarker of age in seabirds. Ricardo’s current research aims include using long-read sequencing to investigate the expression and splicing of risk genes for neuropsychiatric disorders. This work will lead to a better understanding of splicing diversity in human brain regions and will support further studies in the identification of disease-linked isoforms.