Insights Into Functional and Structural Impacts of nsSNPs in XPA-DNA Repairing Gene

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in people. SNPs are valuable resource for exploring the genetic basis of disease. The XPA gene provides a way to produce a protein used to repair damaged DNA. This study used the computational methods to classify SNPs and estimate their probability of being neutral or deleterious. The purpose of this analysis is to predict the effect of nsSNPs on the structure and function of XPA proteins. Data was collected from the NCBI hosted dbSNP. The authors examined the pathogenic effect of 194 nsSNPs in the XPA gene with computational tools. Four nsSNPs (C126S, C126W, R158S, and R227Q) those potentially effect on structure and function of the XPA protein were identified with combination of SIFT, PolyPhen, Provean, PHD-SNP, I-Mutant, ConSurf server and Project HOPE. This is the first comprehensive analysis in which XPA gene variants studied using in silico methods and this research able to gain further insight into XPA protein variants and function.

Investigating Variations/SNPs in AUH Gene Causing 3-Methylglutaconic Aciduria, Type I

A Single nucleotide polymorphisms (SNPs) is a source variation in a genome. The AUH gene gives guidance about how to generate an enzyme named 3-methylglutaconyl-CoA hydratase. Mutations in AUH gene leads to 3-Methylglutaconic aciduria type I disease. The authors used multiple bioinformatics tools SIFT, Provean, PolyPhen, PHD-SNP, I-Mutant, ConSurf server and Project HOPE to isolate missense SNPs that should be deleterious to the structure and function of the AUH protein. This research aims to analyze the impact of missense SNPs on the structure and function of AUH protein. There have been a total of 259 Missense SNPs obtained, of which 13 mutations were identified as deleterious to the structure and function of the AUH protein. This is the first study in relation to AUH gene missense SNPs where most damaging SNPs associated with the AUH gene were examined using computational analysis. This research could be useful in designing specific medicines for treatment of genomic variation diseases.

SNP Association in the Leptin Gene and Beef Quality Traits in Indigenous Sudanese Baggara Cattle

The present study was conducted on 112 Sudanese Baggara bulls (Nyalawi and Mesairi strains) from two separate locations in Darfur and Kordofan, Sudan, raised under dryland farming conditions. A single nucleotide polymorphism (C/T) Arg25Cys in exon 2 of the bovine leptin gene (NC_032653.1) was studied and the association of leptin genotypes with meat quality attributes was evaluated for these two Sudanese Baggara cattle strains which comprise the mainstay of Sudan export and local beef trade. The accuracy of genotyping was checked through PCR-RFLP technique followed by DNA sequencing and analyzed using BioEdit, MEGA6 and project Hope softwares. The genotype frequencies for CC, CT and TT genotypes in Nyalawi strain were 37.5, 39.3 and 23.2%, respectively, whereas the respective genotypic frequencies for Mesairi strain were 46.4, 28.6 and 25%. Significant differences (P<0.05) were found in hot carcass weight, dressing percentage, Myofibril fragmentation index (MFI), water holding capacity (WHC), cooking loss, moisture and fat between the two Baggara cattle strains. Association between the C>T SNP at the leptin gene and carcass weight, dressing and fat percentages was significant (P<0.05). It was concluded that Leptin gene polymorphisms contributed to the observed meat quality differences among these Sudanese cattle strains. This will allow for the use of molecular information in future selection of beef cattle in Sudan. The possible value of the leptin gene and its polymorphisms have been elucidated for the first time in Baggara cattle.

In silico analysis of non-synonymous single nucleotide polymorphisms of human DEFB1 gene

Background Single nucleotide polymorphisms (SNPs) play a significant role in differences in individual’s susceptibility to diseases, and it is imperative to differentiate potentially harmful SNPs from neutral ones. Defensins are small cationic antimicrobial peptides that serve as antimicrobial and immunomodulatory molecules, and SNPs in β-defensin 1 (DEFB1 gene) have been associated with several diseases. In this study, we have determined deleterious SNPs of the DEFB1 gene that can affect the susceptibility to diseases by using different computational methods. Non-synonymous SNPs (nsSNPs) of the DEFB1 gene that have the ability to affect protein structure and functions were determined by several in silico tools—SIFT, PolyPhen v2, PROVEAN, SNAP, PhD-SNP, and SNPs&GO. Then, nsSNPs identified to be potentially deleterious were further analyzed by I-Mutant and ConSurf. Post-translational modifications mediated by nsSNPs were predicted by ModPred, and gene-gene interaction was studied by GeneMANIA. Finally, nsSNPs were submitted to Project HOPE analysis. Results Ten nsSNPs of the DEFB1 gene were found to be potentially deleterious: rs1800968, rs55874920, rs56270143, rs140503947, rs145468425, rs146603349, rs199581284, rs201260899, rs371897938, rs376876621. I-Mutant server showed that nsSNPs rs140503947 and rs146603349 decreased stability of the protein, and ConSurf analysis revealed that SNPs were located in conserved regions. The physiochemical properties of the polymorphic amino acid residues and their effect on structure were determined by Project HOPE. Conclusion This study has determined high-risk deleterious nsSNPs of β-defensin 1 and could increase the knowledge of nsSNPs towards the impact of mutations on structure and functions mediated by β-defensin 1 protein.

In silico analysis of CDC73 gene revealing 11 novel SNPs with possible association to Hyperparathyroidism-Jaw Tumor syndrome

Hyperparathyroidism-Jaw Tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the most deleterious SNPs mutations on CDC73 gene and to predict their influence on the functional and structural levels using different bioinformatics tools. Method: Computational analysis using twelve different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, P-Mut, I-Mutant ,Project Hope, Chimera, COSMIC and dbSNP Short Genetic Variations were used to identify the impact of mutations in CDC73 gene that might be causing jaw tumor. Results: From (733) SNPs identified in the CDC73 gene we found that only Eleven SNPs (G49C, L63P, L64P, D90H, R222G, W231R, P360S, R441C, R441H, R504S and R504H) has deleterious effect on the function and structure of protein and expected to cause the syndrome. Conclusion: Eleven substantial genetic/molecular aberrations in CDC73 gene identified that could serve as diagnostic markers for hyperparathyroidism-jaw tumor (HPT-JT).

In silico analysis of single nucleotide polymorphism (SNPs) in human [BMPR2] gene: دراسة وتحليل الجين (BMPR2) عن طريق (SNPs) باستخدام برمجيات الحاسب الآلي

Background: (BMPR2) gene is encoded gene and cause pulmonary arterial hypertension. Also, it has major role in regulating the growth the maturation of cells. A (BMPR2) gene contains only 25 SNPs as deleterious SNPs and was analyzed in this study. Material and methods: 25 SNPs investigated using the NCBI database (htt: / / www.ncbi.nlm.nih.gov/)and the SNPs were analyzed using six prediction tools: SIFT, Polyphen- 2, I- Mutant, PROVEAN, PhD- SNP and Project Hope. 76% SNPs predict Probably Damaging by POLYPHEN software. the protein stability checked by I- MUTANT and 72% SNPs trend to decrease effected. when used SNPs & GO 52% SNPs were diseased.64% SNPs were deleterious by PROVEAN. There are 20 associated genes, 14 genes share the same protein domains and 13 genes similar in their expression when predicted by GENE MANIA software. Using PROJEC HOPE software to predict the structural effect in function. Result: eight SNPs of 25 SNPs were sharing the same and significant results, so that leads to confirm this result. Conclusions: eight SNPs, rs137852744, rs137852745, rs137852746, rs137852749, rs137852750, rs137852750, rs143740797and rs374694591 were shown to have highly damaging and cause the pulmonary arterial hypertension disease.

The Hidden Wounds of Hurricane Dorian: Why Emergency Response Must Look Beyond Physical Trauma

ABSTRACTProject HOPE, a global health and humanitarian assistance organization, has responded to some of the world’s largest natural disasters and humanitarian and health crises for more than 60 years. As natural disasters increase in frequency and intensity, otherwise effective health systems can become compromised, and - although less visible than traumatic injuries – populations with chronic diseases can be significantly impacted. Emergency preparedness and response efforts must adapt to address issues around continuity of care, access to pharmaceuticals, strengthening cold chain mechanisms, restoring supply chains, and educating patients with chronic illnesses on emergency preparedness. Project HOPE designs medical teams and supply donations to work alongside, rather than parallel to, existing health care infrastructure, laying the foundation for the long-term recovery of the health system.