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The maize brown midrib2 (bm2) gene encodes a methylenetetrahydrofolate reductase that contributes to lignin accumulation.

ABSTRACT: The midribs of maize brown midrib (bm) mutants exhibit a reddish-brown color associated with reductions in lignin concentration and alterations in lignin composition. Here, we report the mapping, cloning, and functional and biochemical analyses of the bm2 gene. The bm2 gene was mapped to a small region of chromosome 1 that contains a putative methylenetetrahydrofolate reductase (MTHFR) gene, which is down-regulated in bm2 mutant plants. Analyses of multiple Mu-induced bm2-Mu mutant alleles confirmed that this constitutively expressed gene is bm2. Yeast complementation experiments and a previously published biochemical characterization show that the bm2 gene encodes a functional MTHFR. Quantitative RT-PCR analyses demonstrated that the bm2 mutants accumulate substantially reduced levels of bm2 transcript. Alteration of MTHFR function is expected to influence accumulation of the methyl donor S-adenosyl-L-methionine (SAM). Because SAM is consumed by two methyltransferases in the lignin pathway (Ye et al., ), the finding that bm2 encodes a functional MTHFR is consistent with its lignin phenotype. Consistent with this functional assignment of bm2, the expression patterns of genes in a variety of SAM-dependent or -related pathways, including lignin biosynthesis, are altered in the bm2 mutant. Biochemical assays confirmed that bm2 mutants accumulate reduced levels of lignin with altered composition compared to wild-type. Hence, this study demonstrates a role for MTHFR in lignin biosynthesis.

SUBMITTER: Tang HM

PROVIDER: S-EPMC4282534 | biostudies-other | 2014 Feb

REPOSITORIES: biostudies-other

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The maize brown midrib2 (bm2) gene encodes a methylenetetrahydrofolate reductase that contributes to lignin accumulation.

Tang Ho Man HM Liu Sanzhen S Hill-Skinner Sarah S Wu Wei W Reed Danielle D Yeh Cheng-Ting CT Nettleton Dan D Schnable Patrick S PS

The Plant journal : for cell and molecular biology 20140110 3

The midribs of maize brown midrib (bm) mutants exhibit a reddish-brown color associated with reductions in lignin concentration and alterations in lignin composition. Here, we report the mapping, cloning, and functional and biochemical analyses of the bm2 gene. The bm2 gene was mapped to a small region of chromosome 1 that contains a putative methylenetetrahydrofolate reductase (MTHFR) gene, which is down-regulated in bm2 mutant plants. Analyses of multiple Mu-induced bm2-Mu mutant alleles confi ...[more]

PMID: 24286468

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Project description:BackgroundCongenital heart disease (CHD), which involve congenital cardiovascular malformations that occur during an embryo stage, may be the result of a complex interaction between genetic factors and environmental factors. The homozygous 677 T/T MTHFR gene and potential factors have been associated with CHD. Our objective was to study associations between potential environmental risk factors and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in CHD.MethodsA total of 346 children with CHD and 237 healthy children were recruited. Their parents were also enlisted in the study and interviewed face-to-face to identify potential environmental risk factors. The MTHFR genotype was analyzed by restriction fragment length polymorphism (RFLP). Interactions between environmental risk factors and MTHFR gene polymorphisms were evaluated by the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S).ResultsThere were significant differences in the occupational statuses of the mothers and their levels of drug exposure during gestation between the controls and the cases (P<0.05). These differences significantly increased offspring CHD risk (occupation: OR =5.45, 95% CI: 3.46-8.58; drug exposure: OR =4.91, 95% CI: 2.18-11.09). The frequency of the MTHFR gene 677 TT polymorphism in the mothers who had offspring with CHD was significantly different from that in the non-CHD controls (P<0.05). The frequency of this polymorphism also significantly differed between the children with CHD and the control group (P<0.05). An interaction was identified between the presence of the homozygous 677 TT genotype in the children and the mothers' occupational statuses (RERI =9.43, CI: 0.06-18.91).ConclusionsA significant interaction was found between the homozygous 677 T/T MTHFR gene in children and the maternal occupational status and level of drug exposure during gestation. Avoiding or reducing the exposure of the risk factors mentioned above, strengthening pre-pregnancy checkups and guidance might help to reduce the risk of CHD.

Project description:BackgroundAcute lymphoblastic leukemia (ALL) is the most common malignancy in children, and methotrexate (MTX) is the key drug for ALL. Studies on the relationship between High-Dose methotrexate (HD-MTX) toxicity and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genes have drawn different conclusions. This study aimed to investigate the relationship between the polymorphism of MTHFR C677T and A1298C genes and the toxicity responses of MTX.MethodsThe MTHFR C677T and A1298C genotypes of 271 children with ALL who received HD-MTX chemotherapy in southern China from September 2017 to June 2021 were analyzed, and the toxicity of HD-MTX was evaluated and analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0.ResultsThe MTHFR C677T and A1298C gene polymorphisms were not correlated with the 48-hour MTX blood concentrations (P>0.05). Unconditional logistic regression model analysis also revealed that the risk of liver function impairment [odds ratio (OR) =1.656, 95% confidence interval (CI): 1.179-2.324, P<0.05] and mucosal damage (OR =1.508, 95% CI: 1.042-2.183, P<0.05) were 1.656 and 1.508 times higher for the heterozygous mutant (CT), and homozygous mutant (TT) mutant type than for the wild-type (CC), wild-type, respectively. The risk of neutropenia and liver function impairment were 0.498 (OR =0.498, 95% CI: 0.251-0.989, P<0.05) and 6.067 (OR =6.067, 95% CI: 1.183-31.102, P<0.05) times higher in low-risk children with CT+TT mutant genotypes than in those with CC wild genotypes, respectively. Furthermore, the risk of mucosal damage was 1.906 times higher in high-risk children with the CT+TT genotype than in those with the CC genotype (OR =1.906, 95% CI: 1.033-3.518, P<0.05). The MTHFR A1298C genotypes differed in the incidence of liver function damage and gastrointestinal toxic reactions in children with ALL. Nonetheless, no increased risk of liver function impairment nor gastrointestinal reactions in children with the heterozygous mutant (AC)+CC mutation was observed.ConclusionsAdvancements in MTHFR genotype testing in children with ALL and the introduction of personalised treatments based on genotype results during HD-MTX chemotherapy will help to predict, prevent, and reduce the occurrence of adverse MTX-related toxic reactions.

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Dataset Information

The maize brown midrib2 (bm2) gene encodes a methylenetetrahydrofolate reductase that contributes to lignin accumulation.

Publications

The maize brown midrib2 (bm2) gene encodes a methylenetetrahydrofolate reductase that contributes to lignin accumulation.

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