Version 1
: Received: 28 March 2024 / Approved: 28 March 2024 / Online: 28 March 2024 (10:52:32 CET)
How to cite:
Chien, W.; Chen, C.; Cheng, M.; Wu, Y.; Gau, S.S. Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder. Preprints2024, 2024031755. https://doi.org/10.20944/preprints202403.1755.v1
Chien, W.; Chen, C.; Cheng, M.; Wu, Y.; Gau, S.S. Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder. Preprints 2024, 2024031755. https://doi.org/10.20944/preprints202403.1755.v1
Chien, W.; Chen, C.; Cheng, M.; Wu, Y.; Gau, S.S. Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder. Preprints2024, 2024031755. https://doi.org/10.20944/preprints202403.1755.v1
APA Style
Chien, W., Chen, C., Cheng, M., Wu, Y., & Gau, S.S. (2024). Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder. Preprints. https://doi.org/10.20944/preprints202403.1755.v1
Chicago/Turabian Style
Chien, W., Yu-Yu Wu and Susan Shurfen Gau. 2024 "Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder" Preprints. https://doi.org/10.20944/preprints202403.1755.v1
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogeneous and complex genetic underpinnings. Our previous microarray gene-expressed profiling identified significantly different neuregulin-2 (NRG2) gene expressions between ASD patients and controls. Thus, we aimed to clarify whether NRG2 is a candidate gene associated with ASD.
The study consisted of two stages. First, we used real-time quantitative PCR in 20 ASDs and 20 controls to confirm the microarray gene expression profiling results. The average NRG2 gene expression level in patients with ASD (3.23±2.80) was significantly lower than that of controls (9.27±4.78, p < 0.001). Next, we resequenced all exons of NRG2 in other 349 ASD subjects, who were compared with super-controls from the Taiwan Biobank using case-control association analysis to determine the existence of mutations or single-nucleotide polymorphisms (SNPs). We identified three SNPs, including two noncoding ones, IVS3 + 13A > G (rs889022) and IVS9 + 32T > A (rs182642591), and one insertion/deletion (indel) SNP, named indel GCCCGGC, rs1323957797, in the NRG2 coding region. The genotype and allele frequency distribution of rs1323957797 significantly differed between ASDs and controls (p < 0.0001).
Our findings showed significant differences in genotype and allele frequency distribution of the indel SNP, rs1323957797, located in the EGF-like domain region at the C-terminal of the NRG2 precursor protein. Together with our findings, the indel SNP mutation was significantly more common in ASDs than controls, leading to lower NRG2 expression than controls, influencing NRG2 function. Our study’s findings suggest that NRG2 is a susceptibility gene for ASD.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
