TRIM4 is associated with neural tube defects based on genome-wide DNA methylation analysis

Autor: Hui Gu, Wenting Luo, Henan Zhang, Xiaowei Wei, Jieting Huang, Hongyan Wang, Zhengwei Yuan, Naixuan Dong, Shanshan Jia, Jia Xue, Yanfu Wang, Yusi Liu, Wei Ma, Dan Liu, Ling Ma, Kun Yu, Yi Guo
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
congenital
hereditary
and neonatal diseases and abnormalities
lcsh:QH426-470
Ubiquitin-Protein Ligases
Mutation
Missense
lcsh:Medicine
Gestational Age
Biology
Methylation
Epigenesis
Genetic
Tripartite Motif Proteins
03 medical and health sciences
Exon
symbols.namesake
0302 clinical medicine
Genetics
medicine
Humans
Molecular Biology
Gene
TRIM4
Genetics (clinical)
Neural tube defects
Sanger sequencing
Whole Genome Sequencing
Research
Gene Expression Profiling
lcsh:R
Neural tube
High-Throughput Nucleotide Sequencing
DNA Methylation
Molecular biology
Human genetics
Up-Regulation
lcsh:Genetics
030104 developmental biology
medicine.anatomical_structure
Real-time polymerase chain reaction
030220 oncology & carcinogenesis
DNA methylation
Trans-Activators
symbols
Female
Genome-Wide Association Study
Developmental Biology
Zdroj: Clinical Epigenetics, Vol 11, Iss 1, Pp 1-13 (2019)
Clinical Epigenetics
ISSN: 1868-7083
1868-7075
DOI: 10.1186/s13148-018-0603-z
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s13148-018-0603-z) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje