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TRIM4 is associated with neural tube defects based on genome-wide DNA methylation analysis
- Source :
- Clinical Epigenetics, Vol 11, Iss 1, Pp 1-13 (2019)
- Publication Year :
- 2019
- Publisher :
- BMC, 2019.
-
Abstract
- Abstract Background Neural tube defects (NTDs) are complex abnormalities associated with gene-environment interactions. The underlying cause has not been determined. Methods Spinal cord tissues from cases with NTDs and healthy controls were collected. Methylation patterns between cases and normal individuals were compared using 450K Infinium Methylation BeadChip Illumina. DNA methylation analysis by pyrosequencing (PyroMark Q96) and mRNA and protein expression were analyzed using real-time quantitative PCR and Western blotting, respectively. Next-generation and Sanger sequencing were used to determine genetic variants in the target genes. Results Spinal cord tissues from cases with NTDs had more hypomethylated than hypermethylated genes. Further evaluation showed that the exon 1 region of TRIM4 was hypomethylated, and TRIM4 mRNA and protein levels were significantly increased in NTDs compared to controls. A rare missense variant (rs76665876) in TRIM4 was found in 3 of the 14 NTD cases but was not related to TRIM4 expression. TRIM4 mRNA levels were significantly increased in cases with hypomethylation and without the rs76665876 variant. Conclusion These findings suggest that spinal cord tissues in cases with NTDs had a different genome-wide methylation pattern compared to controls. Abnormal methylation patterns in TRIM4 in immunity pathways might be involved in NTD pathogenesis. Genetic variants in TRIM4 genes only slightly contribute to the etiology of human NTDs.
- Subjects :
- Neural tube defects
Methylation
TRIM4
Medicine
Genetics
QH426-470
Subjects
Details
- Language :
- English
- ISSN :
- 18687075 and 18687083
- Volume :
- 11
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Clinical Epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.f696e65fb9584372bc39fa8995b5ba71
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13148-018-0603-z