Profiling genetically driven alternative splicing across the Indonesian archipelago.

Autor:	Ibeh N; School of BioSciences, University of Melbourne, Parkville, VIC 3010, Australia; Melbourne Integrative Genomics, University of Melbourne, Parkville, VIC 3010, Australia; Bioinformatics and Cellular Genomics, St Vincents Institute of Medical Research, Fitzroy, VIC 3065, Australia; Human Genomics and Evolution, St Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia., Kusuma P; Genome Diversity and Disease Laboratory, Mochtar Riady Institute of Nanotechnology, Tangerang 15811, Indonesia., Crenna Darusallam C; Genome Diversity and Disease Laboratory, Mochtar Riady Institute of Nanotechnology, Tangerang 15811, Indonesia., Malik SG; Genome Diversity and Disease Laboratory, Mochtar Riady Institute of Nanotechnology, Tangerang 15811, Indonesia., Sudoyo H; Genome Diversity and Disease Laboratory, Mochtar Riady Institute of Nanotechnology, Tangerang 15811, Indonesia., McCarthy DJ; Melbourne Integrative Genomics, University of Melbourne, Parkville, VIC 3010, Australia; Bioinformatics and Cellular Genomics, St Vincents Institute of Medical Research, Fitzroy, VIC 3065, Australia; School of Mathematics and Statistics, Faculty of Science, University of Melbourne, Parkville, VIC 3010, Australia., Gallego Romero I; School of BioSciences, University of Melbourne, Parkville, VIC 3010, Australia; Melbourne Integrative Genomics, University of Melbourne, Parkville, VIC 3010, Australia; Human Genomics and Evolution, St Vincent's Institute of Medical Research, Fitzroy, VIC 3065, Australia; Centre for Genomics, Evolution and Medicine, Institute of Genomics, University of Tartu, 51010 Tartu, Estonia. Electronic address: irene.gallego@svi.edu.au.
Jazyk:	angličtina
Zdroj:	American journal of human genetics [Am J Hum Genet] 2024 Nov 07; Vol. 111 (11), pp. 2458-2477. Date of Electronic Publication: 2024 Oct 08.
DOI:	10.1016/j.ajhg.2024.09.004
Abstrakt:	One of the regulatory mechanisms influencing the functional capacity of genes is alternative splicing (AS). Previous studies exploring the splicing landscape of human tissues have shown that AS has contributed to human biology, especially in disease progression and the immune response. Nonetheless, this phenomenon remains poorly characterized across human populations, and it is unclear how genetic and environmental variation contribute to AS. Here, we examine a set of 115 Indonesian samples from three traditional island populations spanning the genetic ancestry cline that characterizes Island Southeast Asia. We conduct a global AS analysis between islands to ascertain the degree of functionally significant AS events and their consequences. Using an event-based statistical model, we detected over 1,500 significant differential AS events across all comparisons. Additionally, we identify over 6,000 genetic variants associated with changes in splicing (splicing quantitative trait loci [sQTLs]), some of which are driven by Papuan-like genetic ancestry, and only show partial overlap with other publicly available sQTL datasets derived from other populations. Computational predictions of RNA binding activity reveal that a fraction of these sQTLs directly modulate the binding propensity of proteins involved in the splicing regulation of immune genes. Overall, these results contribute toward elucidating the role of genetic variation in shaping gene regulation in one of the most diverse regions in the world. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu