Serine hydroxymethyltransferase 1 and 2: gene sequence variation and functional genomic characterization

Area of Science:

• Biochemistry
• Genetics
• Molecular Biology

Background:

• Serine hydroxymethyltransferase (SHMT) is crucial for neurotransmitter synthesis and metabolism.
• SHMT catalyzes the conversion of serine to glycine and 5,10-methylene-tetrahydrofolate.

Purpose of the Study:

• To resequence SHMT1 and SHMT2 genes and conduct functional genomic studies.
• To investigate the impact of genetic polymorphisms on SHMT gene function and expression.

Main Methods:

• Gene resequencing of SHMT1 and SHMT2.
• Identification and functional analysis of single-nucleotide polymorphisms (SNPs).
• Imputation of variants using '1000 Genomes' data and expression quantitative trait loci (eQTL) analysis.
• Reporter gene assays and correlation analysis with protein expression.

Main Results:

• Identified 87 polymorphisms in SHMT1 and 60 in SHMT2.
• No significant functional effect of 13 non-synonymous SNPs on catalytic activity or protein levels.
• 14 variants significantly associated with SHMT1 mRNA expression; several correlated with SHMT1 protein levels.
• SHMT1 promoter SNP rs669340 implicated in expression variation.
• SHMT1 and SHMT2 expression correlated with other Folate and Methionine Cycle genes.

Conclusions:

• Comprehensive analysis of SHMT1 and SHMT2 sequence variation and functional implications.
• Preliminary evidence suggests co-regulation of SHMT genes with Folate and Methionine Cycle genes.