• 제목/요약/키워드: polyphen-2

검색결과 6건 처리시간 0.017초

In Silico Evaluation of Deleterious SNPs in Chicken TLR3 and TLR4 Genes

  • Shin, Donghyun;Song, Ki-Duk
    • 한국가금학회지
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    • 제45권3호
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    • pp.209-217
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    • 2018
  • The innate immune recognition is based on the detection of microbial products. Toll-like receptors (TLRs) located on the cell surface and the endosome senses microbial components and nucleic acids, respectively. Chicken TLRs mediate immune responses by sensing ligands from pathogens, have been studied as immune adjuvants to increase the efficacy of vaccines. Single nucleotide polymorphisms (SNPs) of TLR3 and TLR4 genes in chicken were associated with resistance and susceptibility to viral infection. In this study, SNPs of chTLR3 and chTLR4 genes were retrieved from public database and annotated with chicken reference genome. Three-dimensional models of the chTLR3 and chTLR4 proteins were built using a Swiss modeler. We identified 35 and 13 nsSNPs in chTLR3 and chTLR4 genes respectively. Sorting Intolerant from Tolerant (SIFT) and Polymorphism Phenotyping v2 (Polyphen-2) analyses, suggested that, out of 35 and 13 nsSNPs, 4 and 2 SNPs were identified to be deleterious in chTLR3 and chTLR4 gene respectively. In chTLR3, 1 deleterious SNP was located in ectodomain and 3 were located in the Toll / IL-1 receptor (TIR) domain. Further structural model of chTLR3-TIR domain suggested that 1 deleterious SNP be present in the B-B loop region, which is important for TIR-TIR domain interactions in the downstream signaling. In chTLR4, the deleterious SNPs were located both in the ectodomain and TIR domain. SNPs predicted for chTLR3 and chTLR4 in this study, might be related to resistance or susceptible to viral infection in chickens. Results from this study will be useful to develop the effective measures in chicken against infectious diseases.

Prediction and Analysis of Breast Cancer Related Deleterious Non-Synonymous Single Nucleotide Polymorphisms in the PTEN Gene

  • Naidu, C Kumaraswamy;Suneetha, Y
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.2199-2203
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    • 2016
  • One of the most common cancer types faced by the women around the world is breast cancer. Among the several low, moderate and high penetrance genes conferring susceptibility to breast cancer, PTEN is one which is known to be mutated in many tumor types. In this study, we predicted and analyzed the impact of three deleterious coding non-synonymous single nucleotide polymorphisms rs121909218 (G129E), rs121909229 (R130Q) and rs57374291 (D107N) in the PTEN gene on the phenotype of breast tumors using computational tools SIFT, Polyphen-2, PROVEAN, MUPro, POPMusic and the GETAREA server.

Novel SLC5A2 Mutations and Genetic Characterization in Korean Patients with Familial Renal Glucosuria

  • Lee, Weon Kyung;Oh, Seung Hwan;Chung, Woo Yeong
    • Childhood Kidney Diseases
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    • 제22권2호
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    • pp.37-41
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    • 2018
  • Purpose: Familial renal glucosuria (FRG, OMIM #233100) is a rare but relatively benign genetic condition characterized by persistent isolated glucosuria with a normal blood glucose level. We report three additional SLC5A2 mutations and examine their phenotypic and genetic characteristics in a Korean FRG cohort. We also reviewed the literature and summarized the genotypes of all Korean patients with FRG. Methods: A genetic analysis was conducted by directly sequencing all 14 exons of the SLC5A2 gene and their flanking regions in six unrelated Korean children with FRG and their family members. Novel non-synonymous single-nucleotide polymorphisms were identified and compared with known mutations that are repeatedly detected in the Korean population. Results: We found two novel mutations [c.274G>A (G92S) and c.1168C>T (L390F)] and one known [c.1382G>A (S461N)] mutation in each family and one recurrent mutation [c.1346G>A (G449D) (rs768392222)] in two pedigrees. The recurrent G449D was predicted to be "possibly damaging," with a score of 0.883 in Polyphen-2, while G92S, L390F, and S461N were predicted to be "probably damaging," with scores of 1.000, 0.999, and 0.996, respectively. Conclusions: Two novel, one previously reported, and one recurrent mutation were identified in six Korean FRG pedigrees as causative mutations of renal glucosuria. Sequence variations in the SLC5A2 gene were frequently detected in children with persistent isolated glucosuria. A long-term follow-up of this FRG cohort is needed to understand how these specific SGLT2 mutations impair kidney function and energy homeostasis.

Identification of Causal and/or Rare Genetic Variants for Complex Traits by Targeted Resequencing in Population-based Cohorts

  • Kim, Yun-Kyoung;Hong, Chang-Bum;Cho, Yoon-Shin
    • Genomics & Informatics
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    • 제8권3호
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    • pp.131-137
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    • 2010
  • Genome-wide association studies (GWASs) have greatly contributed to the identification of common variants responsible for numerous complex traits. There are, however, unavoidable limitations in detecting causal and/or rare variants for traits in this approach, which depends on an LD-based tagging SNP microarray chip. In an effort to detect potential casual and/or rare variants for complex traits, such as type 2 diabetes (T2D) and triglycerides (TGs), we conducted a targeted resequencing of loci identified by the Korea Association REsource (KARE) GWAS. The target regions for resequencing comprised whole exons, exon-intron boundaries, and regulatory regions of genes that appeared within 1 Mb of the GWA signal boundary. From 124 individuals selected in population-based cohorts, a total of 0.7 Mb target regions were captured by the NimbleGen sequence capture 385K array. Subsequent sequencing, carried out by the Roche 454 Genome Sequencer FLX, generated about 110,000 sequence reads per individual. Mapping of sequence reads to the human reference genome was performed using the SSAHA2 program. An average of 62.2% of total reads was mapped to targets with an average 22X-fold coverage. A total of 5,983 SNPs (average 846 SNPs per individual) were called and annotated by GATK software, with 96.5% accuracy that was estimated by comparison with Affymetrix 5.0 genotyped data in identical individuals. About 51% of total SNPs were singletons that can be considered possible rare variants in the population. Among SNPs that appeared in exons, which occupies about 20% of total SNPs, 304 nonsynonymous singletons were tested with Polyphen to predict the protein damage caused by mutation. In total, we were able to detect 9 and 6 potentially functional rare SNPs for T2D and triglycerides, respectively, evoking a further step of replication genotyping in independent populations to prove their bona fide relevance to traits.

In-silico and structure-based assessment to evaluate pathogenicity of missense mutations associated with non-small cell lung cancer identified in the Eph-ephrin class of proteins

  • Shubhashish Chakraborty;Reshita Baruah;Neha Mishra;Ashok K Varma
    • Genomics & Informatics
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    • 제21권3호
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    • pp.30.1-30.13
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    • 2023
  • Ephs belong to the largest family of receptor tyrosine kinase and are highly conserved both sequentially and structurally. The structural organization of Eph is similar to other receptor tyrosine kinases; constituting the extracellular ligand binding domain, a fibronectin domain followed by intracellular juxtamembrane kinase, and SAM domain. Eph binds to respective ephrin ligand, through the ligand binding domain and forms a tetrameric complex to activate the kinase domain. Eph-ephrin regulates many downstream pathways that lead to physiological events such as cell migration, proliferation, and growth. Therefore, considering the importance of Eph-ephrin class of protein in tumorigenesis, 7,620 clinically reported missense mutations belonging to the class of variables of unknown significance were retrieved from cBioPortal and evaluated for pathogenicity. Thirty-two mutations predicted to be pathogenic using SIFT, Polyphen-2, PROVEAN, SNPs&GO, PMut, iSTABLE, and PremPS in-silico tools were found located either in critical functional regions or encompassing interactions at the binding interface of Eph-ephrin. However, seven were reported in nonsmall cell lung cancer (NSCLC). Considering the relevance of receptor tyrosine kinases and Eph in NSCLC, these seven mutations were assessed for change in the folding pattern using molecular dynamic simulation. Structural alterations, stability, flexibility, compactness, and solvent-exposed area was observed in EphA3 Trp790Cys, EphA7 Leu749Phe, EphB1 Gly685Cys, EphB4 Val748Ala, and Ephrin A2 Trp112Cys. Hence, it can be concluded that the evaluated mutations have potential to alter the folding pattern and thus can be further validated by in-vitro, structural and in-vivo studies for clinical management.

한국 재래닭에서 지질대사 관련 유전자에 존재하는 유해성 nsSNP 발굴 및 생물학적 기능 예측 (Discovery of Deleterious nsSNPs on the Genes related to the Lipid Metabolism and Prediction of Changes on Biological Function in Korean Native Chicken)

  • 오재돈;신동현;신상수;윤창;송기덕
    • 한국가금학회지
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    • 제43권4호
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    • pp.263-272
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    • 2016
  • 한국 재래닭은 맛이나 기호성에서 한국 소비자들의 입맛에 적합한 것으로 알려져 있는데, 이러한 한국 재래닭의 특성을 결정짓는 유전적 요소들이 어떤 것들이 있는지 많이 밝혀지지 않았다. 본 연구에서는, 맛을 결정하는 요인 중 하나인 지질의 대사와 관련된 유전자들 내에 존재하는 nsSNP 연구를 통해서, 한국 재래닭의 유전적 특성을 설명하기 위한 자료를 확보하고자 분석을 실시하였다. 지질대사와 관련한 81개 유전자에 대하여 한국 재래닭에 공통으로 존재하는 nsSNP를 139개 동정하였으며, 이 중 9개의 유전자에 존재하는 14개의 nsSNP가 유해성 nsSNP로 확인되었다. 이들 9개 유전자에 대해 단백질 도메인 예측을 실시하였으며, 그 결과, 유해성 nsSNP들에 의해 바뀐 아미노산들이 모두 주요도메인의 외부에 존재함을 알 수 있었다. 이는 한국 재래닭에서 공통으로 발견한 nsSNP들이 유전자의 고유 기능에 큰 영향을 미치기 보다는 다소 미미한 변화를 통해 한국 재래닭 고유의 특성을 형성하는데 더 큰 역할을 한 것으로 사료된다. 이러한 부분들은 차후 실험을 통해 밝혀져야 할 부분이며, 한국 재래닭의 맛과 관련된 형질 개량을 위한 분자육종 기술 개발에 주요한 자료로 활용될 수 있을 것으로 기대되어진다.