Volatile secondary metabolome and transcriptome analysis reveals distinct regulation mechanism of aroma biosynthesis in Syringa oblata and S. vulgaris.

Lilacs have high ornamental value due to their strong aroma. However, the molecular regulatory mechanisms of aroma biosynthesis and metabolism in lilac were largely unclear. In this study, two varieties with distinct aroma, Syringa oblata 'Zi Kui' (faint aroma) and Syringa vulgaris 'Li Fei' (strong aroma), were used for exploring the regulation mechanism of aroma difference. Via GC-MS analysis, a total of 43 volatile components were identified. Terpene volatiles was the most abundant volatiles constituting the aroma of two varieties. Notably, 3 volatile secondary metabolites were unique in 'Zi Kui' and 30 volatile secondary metabolites were unique in 'Li Fei'. Then, a transcriptome analysis was performed to clarify the regulation mechanism of aroma metabolism difference between these two varieties, and identified 6411 differentially expressed genes (DEGs). Interestingly, ubiquinone and other terpenoid-quinone biosynthesis genes were significantly enriched in DEGs. We further conducted a correlation analysis between the volatile metabolome and transcriptome and found that TPS, GGPPS, and HMGS genes might be the key contributors to the differences in floral fragrance composition between the two lilac varieties. Our study improves the understanding in the regulation mechanism of Lilac aroma and would help improve the aroma of ornamental crops by metabolic engineering.

Prenatal nutritional deficiency reprogrammed postnatal gene expression in mammal brains: implications for schizophrenia.

BACKGROUND: Epidemiological studies have identified prenatal exposure to famine as a risk factor for schizophrenia, and animal models of prenatal malnutrition display structural and functional brain abnormalities implicated in schizophrenia. METHODS: The offspring of the RLP50 rat, a recently developed animal model of prenatal famine malnutrition exposure, was used to investigate the changes of gene expression and epigenetic modifications in the brain regions. Microarray gene expression analysis was carried out in the prefrontal cortex and the hippocampus from 8 RLP50 offspring rats and 8 controls. MBD-seq was used to test the changes in DNA methylation in hippocampus depending on prenatal malnutrition exposure. RESULTS: In the prefrontal cortex, offspring of RLP50 exhibit differences in neurotransmitters and olfactory-associated gene expression. In the hippocampus, the differentially-expressed genes are related to synaptic function and transcription regulation. DNA methylome profiling of the hippocampus also shows widespread but systematic epigenetic changes; in most cases (87%) this involves hypermethylation. Remarkably, genes encoded for the plasma membrane are significantly enriched for changes in both gene expression and DNA methylome profiling screens (p = 2.37×10(-9) and 5.36×10(-9), respectively). Interestingly, Mecp2 and Slc2a1, two genes associated with cognitive impairment, show significant down-regulation, and Slc2a1 is hypermethylated in the hippocampus of the RLP50 offspring. CONCLUSIONS: Collectively, our results indicate that prenatal exposure to malnutrition leads to the reprogramming of postnatal brain gene expression and that the epigenetic modifications contribute to the reprogramming. The process may impair learning and memory ability and result in higher susceptibility to schizophrenia.

Association study on the DLG4 gene and schizophrenia in the Chinese Han population.

BACKGROUND: Abnormal expressions of the N-methyl-D-aspartate receptor and its interacting postsynaptic density (PSD) molecules have been hypothesized to be involved in the pathophysiology of schizophrenia. Few studies have carried out association studies with DLG4 gene (coding PSD-95 protein) and sought to validate the results with Asian schizophrenia patients. PATIENTS AND METHODS: To further investigate the significance of DLG4 in Asian schizophrenic patients, we examined seven single-nucleotide polymorphisms (SNPs) within this gene in 1504 unrelated Chinese mainland individuals (893 patients and 611 controls). RESULTS: No association was found between these seven SNPs and schizophrenia within our sample. No significant differences in allele or genotype frequencies between schizophrenic paranoid patients and controls were found. CONCLUSION: Although no allelic or genotypic variances of this gene were observed, the possibility that SNPs within DLG4 represent a positive schizophrenia risk gene cannot be excluded. Our research provided a reference for further research into this gene in other populations.

Association between a COMT polymorphism and clinical response to risperidone treatment: a pharmacogenetic study.

A total of 130 Chinese schizophrenic patients (45 male, 85 female) were enrolled in the study. Clinical efficacy was determined using Brief Psychiatric Rating Scale (BPRS) scores. We genotyped 10 single-nucleotide polymorphisms (SNPs) of the catechol-O-methyl transferase gene (COMT) in our patients and re-examined them for association with changes in BPRS scores after 8 weeks of risperidone monotherapy. COMT is one of the genes that confer susceptibility to schizophrenia, both because of its role in neurotransmitter metabolism and because of its location in the high-risk schizophrenia-related region 22q11. Recent studies also found that COMT functional polymorphisms influenced individual response to antipsychotic medication. Our aim in this study was to explore the influence of COMT polymorphisms on pharmacological response to risperidone in the Chinese population. Statistical analysis revealed a significant association between an upstream COMT SNP, rs9606186, and scores reduction of BPRS in all patients and in the male subgroup but not in the female subgroup (allele analysis: P=0.055 for all, P=0.012 for male patients; genotype analysis: P=0.046 for all, P=0.020 for male patients, uncorrected, odds ratio=3.95). The COMT gene polymorphism, SNP rs9606186, is associated with risperidone therapy efficiency in the Chinese population. This association exhibited a sexually dimorphic difference, which may shed light on the genetics of COMT and its enzymatic sex-dependent mechanism.

No association between the USP7 gene polymorphisms and colorectal cancer in the Chinese Han population.

Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. USP7 is a very important protein with an important role in regulating the p53 pathway, which is critical for genomic stability and tumor suppression. We here genotyped eight SNPs within the USP7 gene and conducted a case-control study in 312 CRC patients and 270 healthy subjects in the Chinese Han population. No significant associations were found for any single SNP and CRC risk. Our data eliminate USP7 as a potential candidate gene towards for CRC in the Han Chinese population.

Association study of APC polymorphisms with colorectal cancer in Han Chinese.

OBJECTIVES: Colorectal cancer (CRC) is a common malignancy with worldwide prevalence. Familial adenomatous polyposis (FAP), a predisposition syndrome of CRC, is caused by germ line mutations in the APC gene. Mutations in APC are thought to be an early event in colorectal tumorigenesis. We hypothesized that common variants in APC might be associated with CRC. DESIGN AND METHODS: A case-control study genotyping ten SNPs was conducted in 312 CRC patients and 270 normal controls in the Chinese Han population. RESULTS: The genotype frequency of rs2019720 showed a significant difference between cases and controls (p=0.046, after Bonferroni correction). For the three pairs of SNPs in strong LD, we carried out haplotype analyses but no significant association was detected. CONCLUSION: Our results suggest that APC polymorphisms might be associated with CRC in the Chinese Han population.

No association between the KCNH1, KCNJ10 and KCNN3 genes and schizophrenia in the Han Chinese population.

Schizophrenia is a common severe mental illness affecting 0.3-2.0% of the world's population. The potassium channels are thought to have a role in modulating electrical excitability in neurons, regulating calcium signaling in oligodendrocytes and regulating action potential duration in presynaptic terminals and GABA release. Previous studies have reported that some potassium channel genes might be candidate genes for susceptibility to schizophrenia. In the present study, we chose three potassium channel genes, KCNH1, KCNJ10, KCNN3 to investigate the role of potassium channels in schizophrenia by genotyping 23 SNPs (9 in KCNH1, 5 in KCNJ10 and 9 in KCNN3) in a Han Chinese sample consisting of 893 schizophrenia patients and 611 healthy controls. No significant difference in allelic or genotypic frequency was revealed between schizophrenia patients and healthy individuals. Nor was a significant difference in haplotypic distribution detected. MDR analysis revealed no gene-gene interaction within the three potassium channel genes. Our study suggests that the 23 SNPs within the three potassium genes we examined do not play a major role in schizophrenia in the Han Chinese population.

Polymorphisms of XRCC4 are involved in reduced colorectal cancer risk in Chinese schizophrenia patients.

BACKGROUND: Genetic factors related to the regulation of apoptosis in schizophrenia patients may be involved in a reduced vulnerability to cancer. XRCC4 is one of the potential candidate genes associated with schizophrenia which might induce colorectal cancer resistance. METHODS: To examine the genetic association between colorectal cancer and schizophrenia, we analyzed five SNPs (rs6452526, rs2662238, rs963248, rs35268, rs2386275) covering ~205.7 kb in the region of XRCC4. RESULTS: We observed that two of the five genetic polymorphisms showed statistically significant differences between 312 colorectal cancer subjects without schizophrenia and 270 schizophrenia subjects (rs6452536, p = 0.004, OR 0.61, 95% CI 0.44-0.86; rs35268, p = 0.028, OR 1.54, 95% CI 1.05-2.26). Moreover, the haplotype which combined all five markers was the most significant, giving a global p = 0.0005. CONCLUSIONS: Our data firstly indicate that XRCC4 may be a potential protective gene towards schizophrenia, conferring reduced susceptibility to colorectal cancer in the Han Chinese population.