A STUDY OF THE STRUCTURE AND THE EXPRESSION OF PROTOONCOGENES IN HUMAN PRIMARY GASTRIC CANCER

The allelic distribution of EcoRI and BamHI fragments of ras family genes between the human primary gastric cancer tissues and the corresponding adjacent normal tissues did not show any differences. Three genotypes of BamHI restriction fragments length polymorphism of c-H-ras were revealed. No significant differences in the RFLPs were observed between normal individuals and gastric cancer patients. Four protooncogenes, c-H-ras, N-ras, c-myc and c-fos, were found to be transcriptionally active in the gastric cancer tissues in some cases examined. The comparison of the expression of these oncogenes between the malignant tissues and the corresponding normal tissues showed differential patterns. The expression of c-H-ras at cellular level was detected with in situ hybridization. The enhanced expression of c-H-ras in the gastric cancer cells was demonstrated, but the degree of the expession among the cancer cells was shown to be heterogeneous. In addition, the enhanced expression of c-H-ras was seen in the inflammatory cells.

Porcine methionine sulfoxide reductase B3:molecular cloning,tissue-specific expression profiles,and polymorphisms associated with ear size in Sus scrofa

Background： In Sus scrofa, methionine sulfoxide reductase B3（MSRB3） is a crucial candidate gene for ear size, and an important conformational trait of pig breeds. However, challenges in MSRB3 c DNA amplification have prevented further identification of MSRB3 allelic variants influencing pig ear size.Results： We cloned a full-length c DNA sequence of porcine MSRB3 by rapid-amplification of c DNA ends. The3,765-bp gene contained a 5＇-untranslated region（UTR）（190 bp）, a coding region（552 bp）, and a 3＇-UTR（3,016 bp） and shared 84 %, 84 %, 87 %, 86 %, and 70 % sequence identities with human, orangutan, mouse, chicken, and zebrafish,respectively. The gene encoded a 183-amino acid protein, which shared 88 %, 91 %, 89 %, 86 %, and 67 % identities with human, orangutan, mouse, chicken, and zebrafish, respectively. Tissue expression analysis using q RT-PCR revealed that MSRB3 was expressed in the heart, liver, lung, kidney, spleen, ear, muscle, fat, lymph, skeletal, and hypothalamic tissues. Three single nucleotide polymorphisms（SNPs） were identified in MSRB3： c.-735 C 〉 T in the 5＇ flanking region,c.2571 T 〉 C in the 3＇-UTR, and a synonymous mutation of c.484 T 〉 C in the coding region. The SNPs c.-735 C 〉 T and c.2571 T 〉 C were significantly associated with ear size in a Large White × Minzhu F2 population other than in Beijing Black pigs. Subsequently, at SNP c.-735 C 〉 T, the m RNA of MSRB3 was significantly higher expressed in ears of individuals with the TT genotype（Minzhu） than those with CC（Large White）.Conclusions： The porcine MSRB3 owned a 3,765-bp full-length c DNA sequence and was detected to express in ear tissue. Two SNPs of this gene were shown to be significantly associated with ear size in a Large White × Minzhu intercross population instead of Beijing Black pig population. What＇s more, the individuals with higher m RNA expression of MSRB3 have larger ear sizes. These results provide useful information for further functional analyses of MSRB3 influencing ear size in pigs.

Application of systems biology to the study of chronic kidney disease

Chronic kidney disease （CKD） is a major public health problem that affects about 10% of the general population. Current approaches to characterize the category and progression of CKD are normally based on renal histopathological results and clinical parameters. However, this information is not sufficient to predict CKD progression risk reliably or to guide preventive interventions. Nowadays, the appearance of systems biology has brought forward the concepts of ＂-omics＂ technologies, including genomics, transcriptomics, proteomics, and metabolomics. Systems biology, together with molecular analysis approaches such as microarray analysis, genome-wide association studies （GWAS）, and serial analysis of gene expression （SAGE）, has provided the framework for a comprehensive analysis of renal disease and serves as a starting point for generating novel molecular diagnostic tools for use in nephrology. In particular, analysis of urinary mRNA and protein levels is rapidly evolving as a non-invasive approach for CKD monitoring. All these systems biological molecular approaches are required for application of the concept of ＂personalized medicine＂ to progressive CKD, which will result in tailoring therapy for each patient, in contrast to the ＂one-size-fits-all＂ therapies currently in use.

Underpinning the soft nature of soak-n-eat rice - A physicochemical and molecular approach

Soak-n-eat rice, a natural treasure of Eastern India, is popular rice based ethnic food item of the tribal peoples of Assam. In the present study, 22 low amylose containing glutinous Bora rice lines were explored for their unique ‘ready-to-eat’ properties, where physicochemical and molecular approach was used to investigate the science behind softness and finally the establishment of trait linked marker associated with this unique soft trait. Very low amylose content, pinholes in kernel, low final viscosity and detection of unique functional groups, made physicochemical properties of soft rice very distinct from normal rice. Polymorphic trait linked markers;a good number of SNPs in trait linked loci and down regulation of those loci during grain filling revealed the unique molecular basis of softness. RM190 is associated with amylose content and softness, confirmed as a trait linked marker by showing heterozygous band in hybrid lines with desired trait. This study may be the first holistic approach on soft rice for its unique soak-n-eat properties and developed hybrid lines may be the source of future environment friendly food.

Transcriptome-wide association studies: a view from Mendelian randomization

Background:Genome-wide association studies(GWASs)have identified thousands of genetic variants that are associated with many complex traits.However,their biological mechanisms remain largely unknown.Transcriptome-wide association studies(TWAS)have been recently proposed as an invaluable tool for investigating the potential gene regulatory mechanisms underlying variant-trait associations.Specifically,TWAS integrate GWAS with expression mapping studies based on a common set of variants and aim to identify genes whose GReX is associated with the phenotype.Various methods have been developed for performing TWAS and/or similar integrative analysis.Each such method has a different modeling assumption and many were initially developed to answer different biological questions.Consequently,it is not straightforward to understand their modeling property from a theoretical perspective.Results:We present a technical review on thirteen TWAS methods.Importantly,we show that these methods can all be viewed as two-sample Mendelian randomization(MR)analysis,which has been widely applied in GWASs for examining the causal effects of exposure on outcome.Viewing different TWAS methods from an MR perspective provides us a unique angle for understanding their benefits and pitfalls.We systematically introduce the MR analysis framework,explain how features of the GWAS and expression data influence the adaptation of MR for TWAS,and re-interpret the modeling assumptions made in different TWAS methods from an MR angle.We finally describe future directions for TWAS methodology development.Conclusions:We hope that this review would serve as a useful reference for both methodologists who develop TWAS methods and practitioners who perform TWAS analysis.