Profiling genetically driven alternative splicing across the Indonesian archipelago
Journal article
Ibeh, Neke, Kusuma, Pradiptajati, Crenna Darusallam, Chelzie, Malik, Safarina G., Sudoyo, Herawati, McCarthy, Davis J. and Gallego Romero, Irene. (2024). Profiling genetically driven alternative splicing across the Indonesian archipelago. American Journal of Human Genetics. 111(11), pp. 2458-2477. https://doi.org/10.1016/j.ajhg.2024.09.004
Authors | Ibeh, Neke, Kusuma, Pradiptajati, Crenna Darusallam, Chelzie, Malik, Safarina G., Sudoyo, Herawati, McCarthy, Davis J. and Gallego Romero, Irene |
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Abstract | 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. |
Year | 2024 |
Journal | American Journal of Human Genetics |
Journal citation | 111 (11), pp. 2458-2477 |
Publisher | Cell Press |
ISSN | 0002-9297 |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.ajhg.2024.09.004 |
PubMed ID | 39383868 |
Scopus EID | 2-s2.0-85207357067 |
PubMed Central ID | PMC11568790 |
Open access | Published as ‘gold’ (paid) open access |
Page range | 2458-2477 |
Funder | National Health and Medical Research Council (NHMRC) |
Australian Research Council (ARC) | |
Wellcome Trust | |
European Union | |
European Regional Development Fund (FEDER) | |
Operational Infrastructure Support (OIS) Program, Victorian Government | |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 07 Nov 2024 |
Publication process dates | |
Accepted | 12 Sep 2024 |
Deposited | 03 Apr 2025 |
ARC Funded Research | This output has been funded, wholly or partially, under the Australian Research Council Act 2001 |
Grant ID | GNT1195595 |
GNT1112681 | |
GNT1162829 | |
DP200101552 | |
GNT2020501 | |
222992/Z/21/Z | |
810645 | |
MOBEC008 | |
Additional information | © 2024 The Author(s). Published by Elsevier Inc. on behalf of American Society of Human Genetics. |
https://acuresearchbank.acu.edu.au/item/91903/profiling-genetically-driven-alternative-splicing-across-the-indonesian-archipelago
Download files
Publisher's version
OA_Ibeh_2024_Profiling_genetically_driven_alternative_splicing_across.pdf | |
License: CC BY-NC-ND 4.0 | |
File access level: Open |
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