J. Francis Borgio
@iau.edu.sa
Associate Professor and Chairman
Imam Abdulrahman Bin Faisal University
Dr. J. Francis Borgio, Chairman, Department of Epidemic Diseases Research, & Associate Professor of Molecular Genetics, Department of Genetic Research at the Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, (Formerly: University Of Dammam), Saudi Arabia. He was a Former-Deputy Chairman, International Indian School Dammam (IISD), one of the biggest school in the Gulf. He is having 12 Years of Experience in the field of Molecular Biology. His Area of Expertise includes: Molecular Genetics, Hemoglobinopathies, Dental Genetics, Genetics of Autism, etc. He is a Principle Investigator or Co-investigator for 10 small and 3 major ongoing funded research projects.
EDUCATION
Trialect Fellowship, Apr 2023, Trialect Fellowship in Covid-19 Variants and Virus-Cell Interactions, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
Trialect Fellowship in Red Blood Cell Physiology, Oct 2018, Clinical Translational Research-Anemia and Red Blood Cells Traineeship, Red Blood Cell Research Group, Institute of Veterinary Physiology, University of Zürich, Zürich, Switzerland
Ph. D., Microbiology , 29 March 2010, Manonmanium Sundaranar University, Tirunelveli, Tamil Nadu, INDIA.
M. Sc., Microbiology, April 2004, Sri Paramakalyani College, Alwarkurichi., Tirunelveli (Dist), Tamil Nadu, INDIA.
RESEARCH, TEACHING, or OTHER INTERESTS
Biochemistry, Genetics and Molecular Biology, Molecular Biology, Microbiology (medical), Genetics
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Omar Mohammed Alakloby, Fatimah Almuqarrab, Johannes Zschocke, Mathias Schmuth, Adnan Abdulkareem, Kholood Alnutaifi, Francis Borgio, Robert Gruber, and Hans Christian Hennies
Springer Science and Business Media LLC
AbstractIchthyoses are a heterogeneous group of cornification disorders. The most common form of ichthyoses is ichthyosis vulgaris (IV) ([OMIM] #146,700), which can be inherited as autosomal semi-dominant mutation in the filaggrin gene (FLG). We present the findings of a study involving 35 Saudi patients with a clinical diagnosis of ichthyosis vulgaris. For identifying the pathogenic mutation of their disease, we used Sanger sequencing analysis of the extracted DNA samples. We also identified the underlying 22 FLG variants, which have been seen before. However, the detected mutations do not involve the common p.R501* c. 2282del4 mutations reported in European populations. Indeed, we did not identify any statistical influence of the homozygous or heterozygous genotypes on the phenotype severity of the disease.
Jawaher Khamis Al-Zahrani, Amira Hassan Al-Abdalall, Mohamed Aly Osman, Lena A. Aldakheel, Nada Faisal AlAhmady, Sumayh A. Aldakeel, Sayed AbdulAzeez, J. Francis Borgio, Medhat A. ElNaggar, Nadiyah M. Alabdallah,et al.
Elsevier BV
J. Francis Borgio, Reem AlJindan, Lujeen H. Alghourab, Rahaf Alquwaie, Razan Aldahhan, Norah F. Alhur, Doaa M. AlEraky, Nehal Mahmoud, Noor B. Almandil, and Sayed AbdulAzeez
MDPI AG
We report on a highly virulent, multidrug-resistant strain of Enterococcus faecalis IRMC827A that was found colonizing a long-term male patient at a tertiary hospital in Khobar, Saudi Arabia. The E. faecalis IRMC827A strain carries several antimicrobial drug resistance genes and harbours mobile genetic elements such as Tn6009, which is an integrative conjugative element that can transfer resistance genes between bacteria and ISS1N via an insertion sequence. Whole-genome-sequencing-based antimicrobial susceptibility testing on strains from faecal samples revealed that the isolate E. faecalis IRMC827A is highly resistant to a variety of antibiotics, including tetracycline, doxycycline, minocycline, dalfopristin, virginiamycin, pristinamycin, chloramphenicol, streptomycin, clindamycin, lincomycin, trimethoprim, nalidixic acid and ciprofloxacin. The isolate IRMC827A carries several virulence factors that are significantly associated with adherence, biofilm formation, sortase-assembled pili, manganese uptake, antiphagocytosis, and spreading factor of multidrug resistance. The isolate also encompasses two mutations (G2576T and G2505A) in the 23S rRNA gene associated with linezolid resistance and three more mutations (gyrA p.S83Y, gyrA p.D759N and parC p.S80I) of the antimicrobial resistance phenotype. The findings through next-generation sequencing on the resistome, mobilome and virulome of the isolate in the study highlight the significance of monitoring multidrug-resistant E. faecalis colonization and infection in hospitalized patients. As multidrug-resistant E. faecalis is a serious pathogen, it is particularly difficult to treat and can cause fatal infections. It is important to have quick and accurate diagnostic tests for multidrug-resistant E. faecalis, to track the spread of multidrug-resistant E. faecalis in healthcare settings, and to improve targeted interventions to stop its spread. Further research is necessary to develop novel antibiotics and treatment strategies for multidrug-resistant E. faecalis infections.
Essam Kotb, Amira H. Alabdalall, Mariam A. Alsayed, Azzah I. Alghamdi, Eida Alkhaldi, Sayed AbdulAzeez, and J. Francis Borgio
MDPI AG
In this study, thirty-seven alkaline protease-producing bacteria were recovered from different regions of Saudi Arabia. The proteolytic strain with the highest productivity was identified as Bacillus sp. Mar64. Maximum productivity of Mar64P alkaline protease was reached at 60 h, pH 9.0, and 45 °C using 1% tyrosine and 0.5% maltose as nitrogen and carbon supplies, respectively. Specific activity was intensified to 8.5-fold with a recovery of 12.4% and SDS—PAGE revealed one band at 28 kDa after enzyme purification. Mar64P was maximally active at 55 °C and pH 11.0 with thermal stability up to 70 °C and pH stability at 7.0–12.0 for 1 h. It was inhibited by EDTA and unaffected by PMSF, therefore tentatively classified as metalloprotease-type. Storage efficacy was effective for up to eight weeks and it was durable in presence of organic solvents (20%, v/v) such as acetonitrile, acetone, and isopropanol upto to 15 days. The enzyme was compatible with dry detergents at both low and high temperature, in addition, was successful in removing various stains such as blood, egg yolk, chocolate, tea, coffee, and sweat. Furthermore, it was successful in removing skin hairs and hydrolyzing gelatin of waste X-ray films. Collectively, due to these unique properties, Mar64P could be considered an environmentally friendly candidate in both detergent and leather industries.
Reem AlJindan, Doaa M. AlEraky, Maha Farhat, Noor B. Almandil, Sayed AbdulAzeez, and Jesu Francis Borgio
MDPI AG
Clostridium perfringens is a spore-forming, Gram-positive anaerobic pathogen that causes several disorders in humans and animals. A multidrug-resistant Clostridium strain was isolated from the fecal sample of a patient who was clinically suspected of gastrointestinal infection and had a recent history of antibiotic exposure and diarrhea. The strain was identified by 16s rRNA sequencing as Clostridium perfringens. The strain’s pathogenesis was analyzed through its complete genome, specifically antimicrobial resistance-related genes. The Clostridium perfringens IRMC2505A genome contains 19 (Alr, Ddl, dxr, EF-G, EF-Tu, folA, Dfr, folP, gyrA, gyrB, Iso-tRNA, kasA, MurA, rho, rpoB, rpoC, S10p, and S12p) antibiotic-susceptible genetic species according to the k-mer-based detection of antimicrobial resistance genes. Genome mapping using CARD and VFDB databases revealed significant (p-value = 1 × 10−26) genes with aligned reads against antibiotic-resistant genes or virulence factors, including phospholipase C, perfringolysin O, collagenase, hyaluronidase, alpha-clostripain, exo-alpha-sialidase, and sialidase activity. In conclusion, this is the first report on C. perfringens from Saudi Arabia that conducted whole genome sequencing of IRMC2505A and confirmed the strain as an MDR bacterium with several virulence factors. Developing control strategies requires a detailed understanding of the epidemiology of C. perfringens, its virulence factors, and regional antimicrobial resistance patterns.
Noor B. Almandil, Maram Adnan Alismail, Hind Saleh Alsuwat, Abdulla AlSulaiman, Sayed AbdulAzeez, and J. Francis Borgio
Frontiers Media SA
BackgroundAutism Spectrum Disorder (ASD) is a multifactorial, neurodevelopmental disorder, characterized by deficits in communication, restricted and repetitive behaviors. ASD is highly heritable in Saudi Arabia; indecencies of affected individuals are increasing.ObjectivesTo identify the most significant genes and SNPs associated with the increased risk of ASD in Saudi females to give an insight for early diagnosis.MethodsPilot case–control study mostly emphasized on the significant SNPs and haplotypes contributing to Saudi females with ASD patients (n = 22) compared to controls (n = 51) without ASD. With the use of allelic association analysis tools, 243,345 SNPs were studied systematically and classified according to their significant association. The significant SNPs and their genes were selected for further investigation for mapping of ASD candidate causal variants and functional impact.ResultsIn females, five risk SNPs at p ≤ 2.32 × 10−05 was identified in association with autism. The most significant exonic variants at chromosome 6p22.1 with olfactory receptor genes (OR12D2 and OR5V1) clustered with high linkage disequilibrium through haplotyping analysis. Comparison between highly associated genes (56 genes) of male and female autistic patients with female autistic samples revealed that 39 genes are unique biomarkers for Saudi females with ASD.ConclusionMultiple variations in olfactory receptor genes (OR5V1 and OR12D2) and single variations on SPHK1, PLCL2, AKAP9 and LOC107984893 genes are contributing to ASD in females of Arab origin. Accumulation of these multiple predisposed coding SNPs can increase the possibility of developing ASD in Saudi females.
Lubna Al Asoom, Maha Alassaf, Najd AlSulaiman, Dhuha Boumarah, Aldana Almubireek, Gaeda Alkaltham, Hussain Alhawaj, Taleb Alkhamis, Nazish Rafique, Ahmed Alsunni,et al.
Informa UK Limited
Effectiveness of
J. Francis Borgio, Rahaf Alhujaily, Rahaf Alquwaie, Maryam Jawad Alabdullah, Eman AlHasani, Wojod Alothman, Rawan Khalid Alaqeel, Aqeelah Salman Alfaraj, Ayidah Kaabi, Norah F. Alhur,et al.
Elsevier BV
Lubna Al Asoom, Maha A Alassaf, Najd S AlSulaiman, Dhuha N Boumarah, Aldana M Almubireek, Gaeda K Alkaltham, Hussain A Alhawaj, Taleb Alkhamis, Nazish Rafique, Ahmed Alsunni,et al.
Informa UK Limited
Background Obesity is a global pandemic that is associated with high morbidity and mortality. Natural herbs are commonly used for weight reduction and appetite suppression. Therefore, we aim to investigate the role and mechanism of Nigella sativa (NS) and ginger on weight reduction and appetite regulation. Methods This experimental study was performed at Imam Abdulrahman Bin Faisal University. Twenty-five female rats were distributed into 5 groups: NS (oral 1000mg/kg), Ginger (500 mg/kg), NS-ginger (both interventions), a positive control (intraperitoneal 50 μg/kg Liraglutide), and a negative control. Each intervention was given for 9 weeks. Food intake and body weight were assessed weekly. Serum lipid profile and peptides involved in appetite control (cholecystokinin (CCK), glucagon-like peptide 1(GLP-1), gastric inhibitory polypeptide (GIP), ghrelin, peptide YY, and orexin) were assayed at the end of the experiment. Results None of the interventions showed a statistically significant difference regarding food consumption or weight gain (p > 0.05). However, the three interventions significantly reduced total cholesterol (TC), NS and NS-ginger significantly increased HDL, NS increased ghrelin and ginger increased orexin. Conclusion The present dose and duration of NS, ginger, or in combination did not demonstrate a significant change in body weight or food consumption in comparison to the negative or positive controls. However, NS or ginger has improved the lipid profile by reducing TC and increasing HDL. In addition, NS or ginger can influence some of the peptides involved in appetite regulation such as the increase in ghrelin induced by NS and the reduction of orexin induced by ginger. We believe that these latter effects are novel and might indicate a promising effect of these natural products on appetite regulation.
J Francis Borgio
Termedia Sp. z.o.o.
More than 25 million DNA variations were discovered as novel including major alleles from Arab population. Exome studies on Arabs discovered >3000 novel nucleotide variants associated with >1200 rare genetic disorders. Reclassification of many pathogenic variant into benign through the Arab database enhance building a detailed and comprehensive map of Arab morbid genome. Intellectual disability stands first with the combined and observed carrier frequency. Genome studies and advanced computational biology discovered interesting novel candidate disease marker variations in many genes from consanguineous families with intellectual disability, neurogenetic disorders, blood and bleeding disorder and rare genetic diseases. Pathogenic variants in C12orf57 gene are prominently associated with the etiology of developmental delay/intellectual impairment. Arab mitogenome exposed hundreds of variations in mtDNA genome and its association with obesity. Further study is needed in genomics to fully comprehend the molecular abnormalities and associated pathogenesis that cause inherited disorders in Arab ancestries.
Johra Khan, Lubna Al Asoom, Ahmad Al Sunni, Nazish Rafique, Rabia Latif, Majed Alabdali, Azhar Alhariri, Majed Aloqaily, Sayed AbdulAzeez, Sadaf Jahan,et al.
MDPI AG
Migraine, as the seventh most disabling neurological disease with 26.9% prevalence in Saudi females, lacks studies on identifying associated genes and pathways with migraines in the Arab population. This case control study aims to identify the migraine-associated novel genes and risk variants. More than 1900 Arab ancestry young female college students were screened: 103 fulfilled the ICHD-3 criteria for migraine and 20 cases confirmed in the neurology clinic were included for the study with age-matched healthy controls. DNA from blood samples were subjected to paired-end whole-exome sequencing. After quality control, 3365343 missense, frameshift, missense splice region variants and insertion–deletion (indels) polymorphisms were tested for association with migraine. Significant variants were validated using Sanger sequencing. A total of 17 (p-value 9.091 × 10−05) functional variants in 12 genes (RETNLB, SCAI, ADH4, ESPL1, CPT2, FLG, PPP4R1, SERPINB5, ZNF66, ETAA1, EXO1 and CPA6) were associated with higher migraine risk, including a stop-gained frameshift (-13-14*SX) variant in the gene RETNLB (rs5851607; p-value 3.446 × 10−06). Gene analysis revealed that half of the significant novel migraine risk genes were expressed in the temporal lobe (p-value 0.0058) of the cerebral cortex. This is the first study exploring the migraine risk of 17 functional variants in 12 genes among Saudi female migraineurs of Arab ancestry using whole-exome sequencing. Half of the significant genes were expressed in the temporal lobe, which expands migraine pathophysiology and early identification using biomarkers for research possibilities on personalised genetics.
Hanan A. Aldossary, Suriya Rehman, B. Rabindran Jermy, Reem AlJindan, Afra Aldayel, Sayed AbdulAzeez, Sultan Akhtar, Firdos Alam Khan, J. Francis Borgio, and Ebtesam Abdullah Al-Suhaimi
MDPI AG
Candida auris (C. auris), an emerging multidrug-resistant microorganism, with limited therapeutical options, is one of the leading causes of nosocomial infections. The current study includes 19 C. auris strains collected from King Fahd Hospital of the University and King Fahad Specialist Hospital in Dammam, identified by 18S rRNA gene and ITS region sequencing. Drug-resistance-associated mutations in ERG11, TAC1B and FUR1 genes were screened to gain insight into the pattern of drug resistance. Molecular identification was successfully achieved using 18S rRNA gene and ITS region and 5 drug-resistance-associated missense variants identified in the ERG11 (F132Y and K143R) and TAC1B (H608Y, P611S and A640V) genes of C. auris strains, grouped into 3 clades. The prophylactic and therapeutic application of hydrothermally synthesized Ag-silicalite-1 (Si/Ag ratio 25) nanomaterial was tested against the 3 clades of clinical C. auris strains. 4wt%Ag/TiZSM-5 prepared using conventional impregnation technique was used for comparative study, and nano formulations were characterized using different techniques. The antibiofilm activity of nanomaterials was tested by cell kill assay, scanning electron microscopy (SEM) and light microscopy. Across all the clades of C. auris strains, 4 wt%Ag/TiZSM-5 and Ag-silicalite-1 demonstrated a significant (p = 1.1102 × 10−16) inhibitory effect on the biofilm’s survival rate: the lowest inhibition value was (10%) with Ag-silicalite-1 at 24 and 48 h incubation. A profound change in morphogenesis in addition to the reduction in the number of C.auris cells was shown by SEM and light microscopy. The presence of a high surface area and the uniform dispersion of nanosized Ag species displays enhanced anti-Candida activity, and therefore it has great potential against the emerging multidrug-resistant C. auris.
P. Sowmiya, T. S. Dhas, D. N. Sai, Jyotsna, N. Anandakumar, V. G. Kumar, M. Ravi, S. Nalini, J. F. Borgio, S. AbdulAzeez,et al.
Pleiades Publishing Ltd
Ayman M. Al-Qaaneh, Fuad H. Al-Ghamdi, Sayed AbdulAzeez, and J. Francis Borgio
MDPI AG
Severe acute respiratory coronavirus-2 (SARS-CoV-2) still presents a public threat and puts extra strain on healthcare facilities. Without an effective antiviral drug, all available treatment options are considered supportive. Tocilizumab as a treatment option has to date shown variable results. In this retrospective study, we aimed to assess predictors of mortality of COVID-19 patients (n = 300) on tocilizumab and the clinical effectiveness of this drug. The results showed that ICU admission OR = 64.6 (95% CI: 8.2, 507.4); age of the patient OR = 1.1 (95% CI: 1.0, 1.1); and number of tocilizumab doses administered by the patient OR(two doses) = 4.0 (95% CI: 1.5, 10.9), OR(three doses) = 1.5 (95% CI: 0.5, 5.1), and OR(four doses or more) = 7.2 (95% CI: 2.0, 25.5) presented strong correlation factors that may be linked to COVID-19 mortality. Furthermore, our study showed the beneficial effects of early administration of tocilizumab OR = 1.2 (95% CI: 1.1, 1.4) and longer hospital length of stay OR = 0.974 (95% CI: 0.9, 1.0) in reducing COVID-19 mortalities. High blood D-dimer concentration OR = 1.1 (95% CI: 1.0, 1.2) and reciprocal blood phosphate concentration OR = 0.008 (95% CI: 0.0, 1.2) were correlated to high mortality under SARS-CoV-2 infection. The short-term effect of a single dose of tocilizumab was a significant increase in blood BUN and liver enzymes (ALT, AST, and LDH) above their normal ranges. Furthermore, it significantly reduced CRP blood concentration, but not to normal levels (13.90 to 1.40 mg/dL, p < 0.001). Assessing the effect of different doses of tocilizumab (in terms of the number of doses, total mg, and total mg/kg administered by the patients) indicated that administering more than one dose may lead to increases in ICU length of stay and hospital length of stay of up to 14 and 22 days after the last dose of tocilizumab (6 to 14, p = 0.06, and 10 to 22, p < 0.001), with no improvement in 28- and 90-day mortality, as confirmed by Kaplan–Meier analysis. There were also clear correlations and trends between the number of doses of tocilizumab and increased blood CO2, MCV, RDW, and D-dimer concentrations and between number of doses of tocilizumab and decreased CRP, AST, and hemoglobin concentrations. Microbiology analysis showed a significant increase in the incidence of infection after tocilizumab administration (28 to 119, p < 0.001) with a median time of incidence within 6 days of the first dose of tocilizumab. A significant correlation was also found between the number of tocilizumab doses and the number of incidences of infections after tocilizumab administration r (298) = 0.396, p = 1.028 × 10−12. Based on these results and depending on the pharmacokinetic parameters of the drug, we recommend single-dose administration of tocilizumab as the optimal dosage for COVID-19 patients who do not have active bacterial infection or liver diseases, to be administered as soon as the patient is admitted to the hospital.
Antonino Giambona, Margherita Vinciguerra, Filippo Leto, Filippo Cassarà, Viviana Tartaglia, Valentina Cigna, Emanuela Orlandi, Francesco Picciotto, Nourah H. Al Qahtani, Eman S. Alsulmi,et al.
Springer Science and Business Media LLC
Noor B. Almandil, Abdulla AlSulaiman, Sumayh A. Aldakeel, Deem N. Alkuroud, Halah Egal Aljofi, Safah Alzahrani, Aishah Al-mana, Asma A. Alfuraih, Majed Alabdali, Fahd A. Alkhamis,et al.
MDPI AG
Autism is a complex disease with genetic predisposition factors. Real factors for treatment and early diagnosis are yet to be defined. This study integrated transcriptome and exome genotyping for identifying functional variants associated with autism spectrum disorder and their impact on gene expression to find significant variations. More than 1800 patients were screened, and 70 (47 male/23 female) with an average age of 7.56 ± 3.68 years fulfilled the DSM-5 criteria for autism. Analysis revealed 682 SNPs of 589 genes significantly (p < 0.001) associated with autism among the putative functional exonic variants (n = 243,345) studied. Olfactory receptor genes on chromosome 6 were significant after Bonferroni correction (α = 0.05/243345 = 2.05 × 10−7) with a high degree of linkage disequilibrium on 6p22.1 (p = 6.71 × 10−9). The differentially expressed gene analysis of autistic patients compared to controls in whole RNA sequencing identified significantly upregulated (foldchange ≥0.8 and p-value ≤ 0.05; n = 125) and downregulated (foldchange ≤−0.8 and p-value ≤ 0.05; n = 117) genes. The integration of significantly up- and downregulated genes and genes of significant SNPs identified regulatory variants (rs6657480, rs3130780, and rs1940475) associated with the up- (ITGB3BP) and downregulation (DDR1 and MMP8) of genes in autism spectrum disorder in people of Arab ancestries. The significant variants could be a biomarker of interest for identifying early autism among Arabs and helping to characterize the genes involved in the susceptibility mechanisms for autistic subjects.
J. Francis Borgio, Hind Saleh Alsuwat, Widyan Alamoudi, Fatma Mohammed Hegazi, Waad Mohammed Al Otaibi, Abdallah M. Ibrahim, Noor B. Almandil, Amani M. Al-Amodi, Yousef M. Alyousef, Emad AlShwaimi,et al.
Elsevier BV
J Sherlin John, , Prathas Selvaraj, T Pushpanathan, B Ravichandran, Sayed AbdulAzeez, J Francis Borgio, , , ,et al.
St. Xavier's College
Assassin bugs are terrestrial predators belonging to the family Reduviidae. Among the 24 subfamilies, harparctorinae is predominant and extensively investigated for biocontrol applications compared to the others subfamilies in Reduviidae. Being natural enemies of phytophagous insects, understanding the phylogeny of these predatory bugs can precise the selection of candidates to employ in insect pest management. In addition to morphological systematics, complete mitochondrial genome sequences provide great insights into the phylogeny for resolving evolutionary complexity. Complete mitochondrial genomes of four potential predatory harpactorinae and one outgroup triatominae were retrieved from NCBI GenBank database. Comparative analysis of the five mitogenomes and the nucleotide sequence between nad1 and nad2 genes were selected as the best option to distinguish. The nucleotide sequence between nad1- nad2 are found to be biased towards A and T similar to their respective complete mitogenomes. Tajima’s test of neutrality suggest that the evolutionary selection at nad1-nad2 was parallel to the complete mitogenome and showed positive and significant (p > 0.1) with high nucleotide diversity. Unequal evolutionary rate at nad1-nad2 between lineages observed in Tajima’s relative rate test and proved the nucleotide sequences of nad1-nad2 between species are highly variable. Comparing the phylogenetic trees generated using the complete mitogenomes and nad1-nad2 genes uncovered the correlation between the trees and having identical branches with varying bootstrap values. Conventionally the highly conserved protein-coding cox1 gene is used for molecular taxonomy whereas this study provides an additional and/or a possible alternative molecular marker for genetic comparative test (the nucleotide sequence between nad1-nad2) to understand the systematics and phylogeny of Reduviidae. The significant nucleotide diversity, high genetic distance and less genetic similarity of the sequence between nad1-nad2 genes among the species studied, Agriosphodrus dohrni, Rhynocoris fuscipes, Scipinia horrida, and Velinus nodipes undoubtedly propose the possible utilization of nad1-nad2 region as distinguishable molecular marker.
Yasser Osman, Tarek Elsharkawy, Tariq Mohammad Hashim, Jumana Abdulwahab Alratroot, Fatima Aljindan, Liqa Almulla, Hind Saleh Alsuwat, Waad Mohammed Al Otaibi, Fatma Mohammed Hegazi, Abdallah M. Ibrahim,et al.
Hindawi Limited
The aim of this study is to investigate the single nucleotide polymorphisms (SNPs) associated with breast cancer in our population of Arab patients. We investigated 26 breast cancer patients and an equal number of healthy age- and sex-matched control volunteers. We examined the exome wide microarray-based biomarkers and screened 243,345 SNPs for their possible significant association with our breast cancer patients. Successfully, we identified the most significant ( p value ≤ 9.14 × 10 − 09 ) four associated SNPs [SNRK and SNRK-AS1-rs202018563G; BRCA2-rs2227943C; ZNF484-rs199826847C; and DCPS-rs1695739G] among persons with breast cancer versus the healthy controls even after Bonferroni corrections ( p value < 2.05 × 10 − 07 ). Although our patients’ numbers were limited, the identified SNPs might shed some light on certain breast cancer-associated functional multigenic variations in Arab patients. We assert on the importance of more extensive large-scale analysis to confirm the candidate biomarkers and possible target genes of breast cancer among Arab ancestries.
Lubna Al Asoom, Johra Khan, Ahmad Al Sunni, Nazish Rafique, Rabia Latif, Majed Alabdali, Sayed AbdulAzeez, and J Francis Borgio
Informa UK Limited
Background Mitochondrial DNA (mtDNA) mutations have been reported in multiple neurological diseases and helped to explain the pathophysiology of these diseases. Similarly, variations in mtDNA might exist in migraine and can explain the effect of low ATP production in the neurons on the initiation of migraine attack. Therefore, in the current study we aim to explore the association of mtDNA mutations on migraine in the Saudi population. Subjects and Methods Over 1950 young Saudi female students were screened for migraine, among that a total of 103 satisfied the ICHD-3 criteria. However, 20 migraine cases confirmed in the neurology clinic and gave consent to participate in the study. Another 20 age-matched healthy controls were also recruited. Mitochondrial sequence variations were filtered from exome sequencing using NCBI GenBank Reference Sequence: NC_012920.1 and analysed using MITOMAP. Genes with significant single nucleotide polymorphisms (SNPs) were investigated by the gene functional classification tool DAVID and functional enrichment analysis of protein–protein interaction networks through STRING 11.5 for the most significant associated genes. Results Genome wide analysis of the mitochondrial sequence variations between the patients with migraine and control revealed the association of 30 SNPs (p < 0.05) in the mitochondrial genome. The highest significance (p = 0.001033) was observed in a coding SNP (rs1603225278) in the CYTB gene and rs386829281 in the region of origin of replication. Twenty-four significant SNPs were in the coding region of nine (ND5, ND4, COX2, COX1, ND3, CYTB, COX3, ND2 and ND1) genes. Conclusion This is the first study to demonstrate the association of mtDNA variations with migraine in the Saudi population. The current findings will help to highlight the significance of mtDNA mutations to migraine pathophysiology and will serve as a reference data for larger national and international studies.
Faisal M Alzahrani, Asma A Al Faris, Layla A Bashawri, Fathelrahman Mahdi Hassan, Omar S El-Masry, Maryam A Aldossary, Osama Al Sultan, J Francis Borgio, Mohammed A Alsahli, and Anne Goodeve
Informa UK Limited
Introduction von Willebrand disease (VWD) is the most prevalent bleeding disease, which is associated with either low levels of von Willebrand factor (VWF) or abnormality in its structure. Three types of the disease have been described; type 1 (VWD1) and 3 (VWD3) are caused by deficiency of VWF and type 2 (VWD2) is caused by production of defective VWF. The aim of the current study was to characterize gene variants of VWF gene; exon 18 in particular, in a cohort of Saudi families as well as healthy control subjects. Methods A total of 19 families comprising 60 subjects of type 1 VWD were enrolled in the study. Participants were divided into 22 index cases, 21 affected family members and 17 unaffected family members ranging in age from 6 to 70 years. Blood samples were collected from all participants to measure activated partial thromboplastin time test (APTT), von Willebrand antigen level (VWF:Ag), Factor VIII activity (FVIII:C) and ristocetin cofactor activity (VWF:RCo), platelet count, determining the ABO blood group and for genetic analysis by Sanger sequencing. Results The results indicated that VWD1 patients have lower levels of VWF and factor VIII than the non-affected family members and the control subjects. In addition, five gene variants were reported in VWF exon 18; of these, c.2365A>G and c.2385T>C were more common in the control group and might be protective from VWD. Discussion In conclusion, VWF levels are influenced by blood group, and there was no association between variants in exon 18 of VWF gene reported in all groups and the disease status; however, blood group analysis and genome-wide genotyping could help to highlight high-risk groups and improve clinical management of VWD.
Arwa Ali Almahasheer, Amal Mahmoud, Hesham El-Komy, Amany I. Alqosaibi, Sultan Aktar, Sayed AbdulAzeez, and J. Francis Borgio
MDPI AG
In this study, five keratinolytic bacteria were isolated from poultry farm waste of Eastern Province, Saudi Arabia. The highest keratinase activity was obtained at 40–45 °C, pH 8–9, feather concentration 0.5–1%, and using white chicken feather as keratin substrate for 72 h. Enhancement of keratinase activity through physical mutagen UV radiation and/or chemical mutagen ethyl methanesulfonate (EMS) resulted in five mutants with 1.51–3.73-fold increased activity over the wild type. When compared with the wild type, scanning electron microscopy validated the mutants’ effectiveness in feather degradation. Bacterial isolates are classified as members of the S8 family peptidase Bacillus cereus group based on sequence analysis of the 16S rRNA and keratinase genes. Interestingly, keratinase KerS gene shared 95.5–100% identity to keratinase, thermitase alkaline serine protease, and thermophilic serine protease of the B. cereus group. D137N substitution was observed in the keratinase KerS gene of the mutant strain S13 (KerS13uv+ems), and also seven substitution variations in KerS26 and KerS26uv of strain S26 and its mutant S26uv. Functional analysis revealed that the subtilisin-like serine protease domain containing the Asp/His/Ser catalytic triad of KerS gene was not affected by the predicted substitutions. Prediction of physicochemical properties of KerS gene showed instability index between 17.5–19.3 and aliphatic index between 74.7–75.7, which imply keratinase stability and significant thermostability. The docking studies revealed the impact of substitutions on the superimposed structure and an increase in binding of mutant D137N of KerS13uv+ems (affinity: −7.17; S score: −6.54 kcal/mol) and seven mutants of KerS26uv (affinity: −7.43; S score: −7.17 kcal/mol) compared to the wild predicted structure (affinity: −6.57; S score: −6.68 kcal/mol). Together, the keratinolytic activity, similarity to thermostable keratinases, and binding affinity suggest that keratinases KerS13uv+ems and KerS26uv could be used for feather processing in the industry.
Asma Y. Alsulaim, Faisal Azam, Tunny Sebastian, Fathelrahman Mahdi Hassan, Sayed AbdulAzeez, J. Francis Borgio, and Faisal M. Alzahrani
Elsevier BV
Norah Ali AlGhamdi, Hind Saleh Alsuwat, J. Francis Borgio, and Sayed AbdulAzeez
Informa UK Limited
Abstract SARS-CoV-2 is causative of pandemic COVID-19. There is a sequence similarity between SARS-CoV-2 and SARS-CoV; however, SARS-CoV-2 RBDs (receptor-binding domain) binds 20-fold strongly with human angiotensin-converting enzyme 2 (hACE2) than SARS-CoV. The study aims to investigate protein–protein interactions (PPI) of hACE2 with SARS-CoV-2 RBD between wild and variants to detect the most influential interaction. Variants of hACE2 were retrieved from NCBI and subjected to determine the most pathogenic nsSNPs. Probability of PPIs determines the binding affinity of hACE2 genetic variants with RBD was investigated. Composition variations at the hACE2 and RBD were processed for PatchDock and refined by FireDock for the PPIs. Twelve nsSNPs were identified as the top pathogenic from SNPs (n = 7489) in hACE2 using eight bioinformatics tools. Eight RBD variants were complexed with 12 nSNPS of hACE2, and the global energy scores (Kcal/mol) were calculated and classified as very weak (–3.93 to −18.43), weak (–18.42 to −32.94), moderate (–32.94 to −47.44), strong (–47.44 to −61.95) and very strong (–61.95 to −76.46) zones. Seven composition variants in the very strong zone [G726R-G476S; R768W-V367F; Y252N-V483A; Y252N-V367F; G726R-V367F; N720D-V367F and N720D-F486L], and three in very weak [P263S-S383C; RBD-H378R; G726R-A348T] are significantly (p < 0.00001) varied for global energy score. Zonation of the five zones was established based on the scores to differentiate the effect of hACE2 and RBD variants on the binding affinity. Moreover, our findings support that the combination of hACE2 and RBD is key players for the risk of infection that should be done by further laboratory studies. Communicated by Ramaswamy H. Sarma
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GRANT DETAILS
Principal Investigator
(2012-2020) Genetic modifiers in networks of interacting genes with extreme HbF levels in Saudi β-thalassemia (Strategic Project) NSTIP, KACST,
Saudi Arabia.
Principal Investigator
2011-2012 Screening of carriers for ATRX (alpha-thalassemia/ mental retardation, X-linked) syndrome in alpha thalassemia patients in Eastern Province, Saudi Arabia. DSR, University of Dammam, Saudi Arabia.
Principal Investigator 2011-2013 Development of simple multiplex PCR assay to detect the prevalent bacterial and fungal infections KACST,
Saudi Arabia.
Co-PI
2013-2014 Prevalence of novel ATRX gene mutations (c.29delA and c.-51_54delAATG) in healthy Saudi population DSR, UoD, KSA.
Co-PI
2012-2014 Molecular nature of point α0 and α+ defects in Saudis by direct DNA sequencing. DSR, UoD, KSA.
Principal Investigator
2012-2014 Interrelationships between gene polymorphisms and dental caries among Saudi children in Eastern Province DSR, UoD, Saudi Arabia.
Co-PI
2012-2014 Studies on genetic variants of 9p21 and 10 loci in the development of coronary artery disease in population of the Eastern Province of Saudi Arabia DSR, UoD, Saudi Arabia.
Principal Investigator
2013-2015 Sequence variants of the AHSP gene in Saudi subjects with α-thalassemia and/or β-thalassemia mutations DSR, UoD, Dammam, KSA.
Co-PI
2014-2016 Microarray gene profiling of sickle cell disease with cardiovascular complications DSR, UoD, KSA.
Principal Investigator
2015-2016 Development of simple PCR method f
RESEARCH OUTPUTS (PATENTS, SOFTWARE, PUBLICATIONS, PRODUCTS)
US PATENT
1. Borgio, JF., AbdulAzeez, S., Al-Muhanna, F., Al-Ali, A.K. Primer Compositions For Detecting Thalassemia. (United States Patent and Trademark Office, United States Patent Application 20210285051; Filing Date: 27th May 2021), Published on 16th Sep 2019; Published by United States Patent and Trademark Office.
2. Borgio, JF., AbdulAzeez, S., Al-Muhanna, F., Al-Ali, A.K. Single tube multiplex PCR method for the detection of HBA1, HBA2 and HBA12 genes in Saudis. (United States Patent and Trademark Office, United States Patent Application 20200239956; Filing Date: 25th Jan 2019), Published on 07/30/2020; Patent No: “US 11,118,229 B2” on 14th Sep 2021. Granted by United States Patent and Trademark Office.
3. Al-Ali, AK., Borgio, JF., Nasserullah, Z., AbdulAzeez, S., Al-Jarrash, S. Sequence specific primer pool for multiplex PCR and method of detecting microbial infection in thalassemia patients" Filed on 21 Oct 2014. Patent No: “US 9863009 B2” on 9th Jan 2018. Granted by United States Patent and Trademark Office.
CONSULTANCY
Consultant Supervisor
2020-2021 Study of antibiotic resistance genes of Candia auris and the nanoparticles as a potential therapeutic. PI: Ms Hanan No: 2021-182-IRMC DSR, IAU, KSA.
Industry, Institute, or Organisation Collaboration
Principal Investigator (2018), Ensure quality on RNA extraction protocol, MOLEQULE-ON, New Zealand