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Identification of Functional SNPs in BARD1 Gene and In Silico Analysis of Damaging SNPs: Based on Data Procured from dbSNP Database
"... Background: The BARD1 gene encodes for the BRCA1-associated RING domain (BARD1) protein. Germ line and somatic mutations in BARD1 are found in sporadic breast, ovarian and uterine cancers. There is a plethora of single nucleotide polymorphisms (SNPs) which may or may not be involved in the onset of ..."
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Background: The BARD1 gene encodes for the BRCA1-associated RING domain (BARD1) protein. Germ line and somatic mutations in BARD1 are found in sporadic breast, ovarian and uterine cancers. There is a plethora of single nucleotide polymorphisms (SNPs) which may or may not be involved in the onset of female cancers. Hence, before planning a larger population study, it is advisable to sort out the possible functional SNPs. To accomplish this goal, data available in the dbSNP database and different computer programs can be used. To the best of our knowledge, until now there has been no such study on record for the BARD1 gene. Therefore, this study was undertaken to find the functional nsSNPs in BARD1. Result: 2.85 % of all SNPs in the dbSNP database were present in the coding regions. SIFT predicted 11 out of 50 nsSNPs as not tolerable and PolyPhen assessed 27 out of 50 nsSNPs as damaging. FastSNP revealed that the rs58253676 SNP in the 39 UTR may have splicing regulator and enhancer functions. In the 59 UTR, rs17489363 and rs17426219 may alter the transcriptional binding site. The intronic region SNP rs67822872 may have a medium-high risk level. The protein structures 1JM7, 3C5R and 2NTE were predicted by PDBSum and shared 100 % similarity with the BARD1 amino acid sequence. Among the predicted nsSNPs, rs4986841, rs111367604, rs13389423 and rs139785364 were identified as deleterious and damaging by the SIFT and PolyPhen programs. Additionally, I-Mutant showed a decrease in stability for these nsSNPs upon mutation. Finally, the ExPASy-PROSIT program revealed that the predicted deleterious mutations are contained in the ankyrin ring and
Alternative 5′ untranslated regions are involved in expression regulation of human heme oxygenase-1. PLoS One 2013, 8, Article e77224
"... The single nucleotide polymorphism rs2071746 and a (GT)n microsatellite within the human gene encoding heme oxygenase-1 (HMOX1) are associated with incidence or outcome in a variety of diseases. Most of these associations involve either release of heme or oxidative stress. Both polymorphisms are loc ..."
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The single nucleotide polymorphism rs2071746 and a (GT)n microsatellite within the human gene encoding heme oxygenase-1 (HMOX1) are associated with incidence or outcome in a variety of diseases. Most of these associations involve either release of heme or oxidative stress. Both polymorphisms are localized in the promoter region, but previously reported correlations with heme oxygenase-1 expression remain not coherent. This ambiguity suggests a more complex organization of the 5 ’ gene region which we sought to investigate more fully. We evaluated the 5 ‘ end of HMOX1 and found a novel first exon 1a placing the two previously reported polymorphisms in intronic or exonic positions within the 5 ’ untranslated region respectively. Expression of exon 1a can be induced in HepG2 hepatoma cells by hemin and is a repressor of heme oxygenase-1 translation as shown by luciferase reporter assays. Moreover, minigene approaches revealed that the quantitative outcome of alternative splicing within the 5 ’ untranslated region is affected by the (GT)n microsatellite. This data supporting an extended HMOX1 gene model and provide further insights into expression regulation of heme oxygenase-1. Alternative splicing within the HMOX1 5 ' untranslated region contributes to translational regulation and is a mechanistic feature involved in the interplay between genetic variations, heme oxygenase-1
Differential expression of novel adiponectin receptor-1 transcripts in skeletal muscle of subjects with normal glucose tolerance and type 2 diabetes
- Diabetes
, 2011
"... OBJECTIVE—Adiponectin receptor-1 (AdipoR1) expression in skeletal muscle has been suggested to play an important role in insulin resistance and diabetes. We aimed at evaluating the presence of novel AdiopR1 splice variants in human muscle and their regulation under physiological and pathophysiologic ..."
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OBJECTIVE—Adiponectin receptor-1 (AdipoR1) expression in skeletal muscle has been suggested to play an important role in insulin resistance and diabetes. We aimed at evaluating the presence of novel AdiopR1 splice variants in human muscle and their regulation under physiological and pathophysiological states. RESEARCH DESIGN AND METHODS—AdipoR1 59UTR mRNA transcripts, predicted from bioinformatics data, were eval-uated in fetal and adult human tissues. Expression and function of the identified transcripts were assessed in cultured human skeletal muscle cells and in muscle biopsies obtained from indi-viduals with normal glucose tolerance (NGT) and type 2 diabetes (n = 49). RESULTS—Screening of potential AdipoR1 59UTR splice variants revealed a novel highly abundant muscle transcript (R1T3) in ad-dition to the previously described transcript (R1T1). Unlike R1T1,
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"... The promoter of human telomerase reverse transcriptase is activated during liver regeneration and hepatocyte proliferation. ..."
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The promoter of human telomerase reverse transcriptase is activated during liver regeneration and hepatocyte proliferation.
Short Title: Gene-specific antibodies for SP-A1 Corresponding author:
"... The human surfactant protein A (SP-A) locus consists of two functional genes (SP-A1, SP-A2) with gene specific products exhibiting qualitative and quantitative differences. The aim here was two-fold: 1) generate SP-A1 gene-specific antibody, and 2) use this to assess gene-specific SP-A content in th ..."
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The human surfactant protein A (SP-A) locus consists of two functional genes (SP-A1, SP-A2) with gene specific products exhibiting qualitative and quantitative differences. The aim here was two-fold: 1) generate SP-A1 gene-specific antibody, and 2) use this to assess gene-specific SP-A content in the bronchoalveolar lavage fluid (BALF). An SP-A1 specific polyclonal antibody (hSP-A1_Ab68-88_Col) was raised in chicken and its specificity determined by immunoblot and ELISA using mammalian CHO cell-expressed SP-A1 and SP-A2 variants, and by immunofluorescence with stably transfected CHO cell lines expressing SP-A1 or SP-A2 variants. SP-A1 content was evaluated according to age and lung status. A gradual decrease (p<0.05) in SP-A1/SP-A ratio was observed in healthy subjects (HS) with increased age, although no significant change was observed in total SP-A content among age groups. Total SP-A and SP-A1 content differed significantly between alveolar proteinosis (AP) patients and HS, with no significant difference observed in SP-A1/SP-A ratio between AP and HS.
Floros J. Characterization of a human surfactant protein A1 (SP-A1)
, 2006
"... Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health ..."
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Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health
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"... Abstract. Epstein-Barr virus (EBV)-associated naso-pharyngeal carcinoma (NPC) is a squamous cell cancer endemic in Southern China and Southeast Asia. It has been shown that inflammatory and immune responses during EBV infection contribute to the development of NPC. The complement receptor 2 (CR2) ge ..."
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Abstract. Epstein-Barr virus (EBV)-associated naso-pharyngeal carcinoma (NPC) is a squamous cell cancer endemic in Southern China and Southeast Asia. It has been shown that inflammatory and immune responses during EBV infection contribute to the development of NPC. The complement receptor 2 (CR2) gene plays central roles during inflammatory and immune responses and, therefore, is a good candidate susceptibility gene for NPC. We performed PCR-based sequencing to identify multiple single-nucleotide polymorphisms (SNPs) within the exon regions of the CR2 gene in a Cantonese population. Two SNPs were screened in 528 NPC patients and 408 normal individuals to perform a case-control study matched according to age, gender and resi-dence. Furthermore, we cloned the entire 5'-UTR and entire CR2 promoter into a luciferase report system and compared the luciferase activities between the different allelic constructs. A SNP in the 5'-UTR of CR2 (24 T/C, rs3813946) showed a significant association (P<0.01) with NPC in the Cantonese population studied. The subjects were categorized into 2 age groups: group 1, age ≤45 years and group 2, age>45 years. In group 1, the allelic frequencies of 24 T/C in the patients were significantly different from those of the controls (P=0.0034). The odds ratio (OR=1.81) also indicated a higher risk of NPC in individuals who carried the minor allele C. All constructs exerted allelic differences on luciferase activities, but only the susceptible allele +24C construct showed increased activity. Our findings implicate CR2 as a susceptibility gene for NPC and suggest that enhanced CR2 expression may be involved in the oncogenesis and development of NPC.
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. DOI: 10.1093/abbs/gmn004. The optional long 5 0-untranslated region of human ACAT1 mRNAs impairs the production of ACAT1 protein by promo
"... We have previously reported that human ACAT1 mRNAs produce the 50 kDa protein using the AUG 1397 – 1399 initiation codon, and also a minor 56 kDa isoform using the upstream in-frame GGC1274 – 1276 initiation codon. The GGC 1274 – 1276 codon is located at the optional long 5 0-untranslated region (5 ..."
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We have previously reported that human ACAT1 mRNAs produce the 50 kDa protein using the AUG 1397 – 1399 initiation codon, and also a minor 56 kDa isoform using the upstream in-frame GGC1274 – 1276 initiation codon. The GGC 1274 – 1276 codon is located at the optional long 5 0-untranslated region (5 0-UTR, nt 1–1396) of the mRNAs. The DNA sequences corresponding to this 5 0-UTR are located in two different chromosomes, 7 and 1. In the current work, we report that the optional long 5 0-UTR significantly impairs the production of human ACAT1 protein initiated from the AUG 1397 – 1399 codon, mainly by promoting its mRNA decay. The western blot analyses indicated that the optional long 5 0-UTR potently impaired the production of different proteins initiated from the AUG 1397 – 1399
female rat preoptic
"... Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor a transcripts with alternative 5 0-untranslated regions in the ..."
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Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor a transcripts with alternative 5 0-untranslated regions in the
COMPUTATIONAL ANALYSIS OF DISEASE ASSOCIATED nsSNPs in MMP2
"... MMPs have significant role in pathological processes and are associated with cancer invasion, and metastasis, cartilage destruction in arthritis. Non-synonymous single nucleotide polymorphisms (nsSNPs) occurring in protein coding regions of MMP potentially affect their function, and results in disea ..."
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MMPs have significant role in pathological processes and are associated with cancer invasion, and metastasis, cartilage destruction in arthritis. Non-synonymous single nucleotide polymorphisms (nsSNPs) occurring in protein coding regions of MMP potentially affect their function, and results in diseases. In this study we performed an insilco analysis of SNPs associated with MMP2 genes. Total of 683 SNPs are reported for MMP2 gene, coding region. In that only 39 are nsSNPs and 46 SNPs are in UTRs, 277 SNPs are in intronic region of mRNA. Our postulation is based on nsSNPs in the coding region as well as SNPs in the UTR region. Only 8SNPs out of 39nsSNP were identified as deleterious and had significant impact in structural stability which was analyzed using modeled and mutant proteins and native protein structures. Hence, these SNPs can be used for the larger population based studies based on MMP2 associated diseases.
