Hamdi Jarjanazi | Arabian Gulf University (original) (raw)

Papers by Hamdi Jarjanazi

Environmental Science & Technology, 2012

An ecosystem perspective to restoring beneficial uses in Areas of Concern can be interpreted as a... more An ecosystem perspective to restoring beneficial uses in Areas of Concern can be interpreted as a shift from the traditional elucidation of simple cause−effect relationships to a multicausal way of thinking that more effectively accommodates ecosystem complexity. This holistic management paradigm has also pervaded the contemporary ecological modeling practice, making compelling the adoption of more sophisticated ecosystem modeling tools. In this study, our primary objective is to develop a Bayesian hierarchical network of simple ecological models for Lake Simcoe, Ontario, Canada, aiming to establish a realistic representation of the causal connections among exogenous nutrient loading, ambient nutrient conditions, and epilimnetic plankton dynamics. In particular, we used a spatially explicit simple mass-balance model forced with idealized sinusoidal loading to predict total phosphorus concentrations. A structural equation model was then used to delineate the interplay among nutrients, ambient light conditions, phytoplankton, and herbivorous biomass. Our analysis highlights the strength of the causal linkages between total phosphorus and water clarity with phytoplankton as well as the capacity of zooplankton grazing to modulate the algal standing crop. Our Bayesian network is also used to examine the exceedance frequency of threshold values for total phosphorus (15 μg/L) and chlorophyll a (4 μg/L) concentrations under scenarios of phosphorus loading reduction. Our study suggests that a 15% phosphorus loading decrease will still result in >25% violations of the 4 μg chla/L value in the two embayments of Lake Simcoe (Cook's Bay and Kempenfelt Bay). The TP levels will decrease in response to the exogenous loading reductions and this improvement will be primarily manifested in the northcentral segments of the system.

Journal of Great Lakes Research, 2011

Climate change is anticipated to have major physical and biological effects on aquatic ecosystems... more Climate change is anticipated to have major physical and biological effects on aquatic ecosystems. Changes to the thermal regime of lakes such as shorter duration of ice-cover, earlier onset of stratification and an increase in the length of the stratified period have already been observed in some lakes in North America and Europe. Using vertical temperature profiles of Lake Simcoe during the open-water period from 1980 to 2008 we evaluated trends in water column stability, the onset of stratification and the timing of fall turnover at three stations situated in the lake's two bays and its main basin. Dramatic changes were observed at the three stations; each stratified earlier in the spring, mixed later in the fall and remained stratified for more than a month longer in 2008 compared to 1980. Long-term monotonic trends in the timing of the onset of thermal stratification, fall mixing and duration of stratification were significant. These trends resulted from changes in water column density that are strongly correlated with increasing average air temperatures over time, indicating that climate warming has had a significant effect on the thermal regime of Lake Simcoe.

We present a Bayesian variable selection procedure that is applicable to genomewide studies invol... more We present a Bayesian variable selection procedure that is applicable to genomewide studies involving a combination of clinical, gene expression and genotype information. We use the Mode Oriented Stochastic Search (MOSS) algorithm of Dobra and Massam (2010) to explore regions of high posterior probability for regression models involving discrete covariates and to perform hierarchical log-linear model search to identify the most relevant associations among the resulting subsets of regressors. We illustrate our methodology with simulated data, expression data and SNP data.

Annals of Human Biology, 2014

The geographical location of Egypt at the crossroads of several major cultural areas between Nort... more The geographical location of Egypt at the crossroads of several major cultural areas between North Africa and the Middle East has contributed to its population history. To analyse the genetic structure of the population living in two geographical parts of Egypt. A sample of 112 Egyptians from the North African part of Egypt (Ismailia sample) and a sample of 52 Egyptians from the Asian part Sinai, have been analysed using 10 Alu insertion polymorphisms. The results of the present study showed a significant genetic difference between the Sinai and Ismailia samples. The latter showed an evident genetic affinity with North African populations; whereas the Sinai sample was found to be genetically closer to the Middle East populations. The Sinai sample showed a low average heterozygosity, unlike that found in the Ismailia sample. This study provides new insights into the genetic structure of the Egyptian population living in a land bridge between Africa and Asia. Results suggest a genetic discontinuity between the Sinai population and that of the North African part of Egypt. This discontinuity would have been maintained thanks to geo-climatic and social factors.

Inland Waters, 2013

Thermophilic Campylobacter species have been implicated in human gastrointestinal infections and ... more Thermophilic Campylobacter species have been implicated in human gastrointestinal infections and can occur in agricultural run off, sewage discharges, and the feces of domestic and wild animals including birds. A 2-year study was designed to investigate the occurrence of the primary thermophilic Campylobacter species (C. jejuni, coli, and lari) associated with human disease at 5 recreational beaches on Lake Simcoe, Ontario, Canada. A biweekly sampling program involved collecting water samples across 3 depth zones (sand pore water and ankle-and chest-depth waters). To identify the potential sources of contamination, samples were also collected from 4 neighboring rivers corresponding to selected beaches, a few fresh seagull and Canada geese fecal droppings on beaches, and a stormwater outfall. Water and fecal samples were processed for Campylobacter spp. isolation and detection using a minimum probable number culture enrichment protocol. Thermophilic Campylobacter spp. generally occurred infrequently and at low concentrations (≤30 cells L −1 ) at all sampling locations; they were detected in 12% of water samples from beaches (n = 289) compared to 14% from rivers (n = 100). C. jejuni and C. lari were the species most commonly detected. Nine isolates identified as unknown Campylobacter spp. were further sequenced and shown to be more closely related to Arcobacter spp. At beaches, thermophilic Campylobacter spp. were generally detected more often in sand pore water than in ankle-or chest-depth water. The study suggests that sand, rivers, and bird droppings could be potential sources of Campylobacter spp. contamination at Lake Simcoe recreational beaches.

Biomarkers in Cancer, 2015

Inconsistency in the reported associations between the A66G polymorphism in the methionine syntha... more Inconsistency in the reported associations between the A66G polymorphism in the methionine synthase reductase (MTRR) gene and colorectal cancer (CRC) prompted a meta-analysis, so that we could obtain a more precise estimate. Databases searches of the published literature yielded 20 case-control studies from 17 articles (8,371 cases and 12,574 controls). We calculated pooled odds ratios (ORs) and 95% confidence intervals in three genetic comparisons (A allele, G allele, and A/G genotype). We found no evidence of overall associations between MTRR A66G and CRC risk (OR 0.96-1.05, P = 0.12-0.44). This was materially unchanged when reanalyzed without the Hardy-Weinberg equilibrium (HWE)-deviating studies (OR 0.97-1.06, P = 0.11-0.65). In the A allele comparison, however, outlier treatment generated significant protection (OR 0.91, P = 0.01). Combined removal of the outliers and HWE-deviating studies reflected this summary effect (OR 0.90, P = 0.01) as did the pooled OR from high-quality studies (OR 0.90, P = 0.01). Only the Asian subgroup showed significant (both at P = 0.05) A allele (OR 1.13) and A/G genotype (OR 0.88) associations. In conclusion, post-outlier A allele effects were protective. Our study also suggests ethnic-specific associations with Asian susceptibility and protection in the A allele and A/G genotype comparisons, respectively. Folate status showed no association of this polymorphism with CRC.

Journal of Gastrointestinal Cancer, 2015

Reported associations of ACE polymorphisms with gastric cancer have been inconsistent, prompting ... more Reported associations of ACE polymorphisms with gastric cancer have been inconsistent, prompting a meta-analysis of 12 published case-control studies where we estimated risk (odds ratio [OR]). We searched MEDLINE through PubMed and EMBASE for suitable articles that had case-control design with gastric cancer as outcome. In this meta-analysis, our overall findings were subjected to modifier analyses (outlier and sensitivity treatments). We also performed subgroup analysis based on ethnicity (German and Japanese) and histological subtype (intestinal and diffuse). Significance of the protective effects among homozygote carriers of the II genotype (OR 0.54-0.63, P = 0.01-0.02) disappeared with outlier analysis (OR 0.81-0.88, P = 0.12-0.14). Among DD homozygotes, this treatment altered the direction of association from weak protection (OR 0.95-0.96, P = 0.79-0.82) to increased risk (OR 1.13-1.19, P = 0.14-0.16). No significant associations were observed among ID genotype carriers (OR 0.91-0.94, P = 0.69-0.72). Japanese pooled effects varied across the genotype comparisons (OR 0.93-1.06, P = 0.54-0.72). Sensitivity treatment demonstrated robustness of the II genotype, but not the other two, both in overall and subgroup analyses. Histological subtype analysis yielded protection from intestinal cancer across the comparisons (OR 0.38-0.71, P = 0.15-0.50) but variable results for the diffuse type (OR 0.59-1.32, P = 0.19-0.92). In summary, carriers of the ACE II genotype appear to be protected from gastric cancer, regardless of ethnicity or tumor type.

Human genomics, 2006

Although highly penetrant alleles of BRCA1 and BRCA2 have been shown to predispose to breast canc... more Although highly penetrant alleles of BRCA1 and BRCA2 have been shown to predispose to breast cancer, the majority of breast cancer cases are assumed to result from the presence of low-moderate penetrant alleles and environmental carcinogens. Non-synonymous single nucleotide polymorphisms (nsSNPs) are hypothesised to contribute to disease susceptibility and approximately 30 per cent of them are predicted to have a biological significance. In this study, we have applied a bioinformatics-based strategy to identify breast cancer-related nsSNPs from 981 carcinogenesis-related genes expressed in breast tissue. Our results revealed a total of 367 validated nsSNPs, 109 (29.7 per cent) of which are predicted to affect the protein function (functional nsSNPs), suggesting that these nsSNPs are likely to influence the development and homeostasis of breast tissue and hence contribute to breast cancer susceptibility. Sixty-seven of the functional nsSNPs presented as commonly occurring nsSNPs (min...

BioTechniques, 2002

... 2002 May;32(5):1006, 1008, 1010. Modified rapid expansion detection method to analyze Cag/CTG... more ... 2002 May;32(5):1006, 1008, 1010. Modified rapid expansion detection method to analyze Cag/CTG repeat expansions. Jarjanazi H, Ozcelik H. Mount Sinai Hospital, Toronto, Ontario, Canada. PMID: 12019772 [PubMed - indexed for MEDLINE]. Publication Types: ...

Archives of Gynecology and Obstetrics, 2014

Reported associations of progesterone receptor gene polymorphism (PROGINS) with endometriosis hav... more Reported associations of progesterone receptor gene polymorphism (PROGINS) with endometriosis have been inconsistent. To evaluate the association between the PROGINS polymorphism and the risk of endometriosis. A meta-analysis of 12 published case-control studies with a total sample size of 3,321 (1,323 cases/1,998 controls) was performed. We estimated the risk (odds ratio [OR] 95 % confidence intervals) of endometriosis association with the PROGINS polymorphism. An association between the presence of the variant allele and risk of endometriosis was found, more in the homozygous and recessive models (OR 1.41-1.43, p = 0.15-0.17), and less in the dominant and co-dominant models (OR 1.22, p = 0.11-0.15). Reanalysis without the studies whose controls deviated from the Hardy-Weinberg Equilibrium did not materially alter the dominant and co-dominant effects (OR 1.19-1.22, p = 0.19-0.32), but exacerbated the homozygous and recessive effects (OR 1.59, p = 0.09). The subgroups based on geography showed increased risk associations, consistently significant in the European (OR 1.52-2.72, p = 0.0008-0.03) but not in the Brazilian studies, where ORs ranged from reduced (OR 0.70-0.74, p = 0.54-0.61) to increased (OR 1.11, p = 0.75) risks. Heterogeneity was confined in all comparisons to the dominant and co-dominant models (I (2) = 38-70 %), except in the European subgroup, which had zero heterogeneity (I (2) = 0 %) in all genetic models, as did all homozygous and recessive effects. This meta-analysis provides a comprehensive profile of the role of the PROGINS polymorphism in endometriosis by exploring the magnitude of the summary effects with modifier analysis. This magnitude is expressed with modulation or exacerbation of the summary effects, as defined by the parameters of the analysis. Thus, the results showed trend towards an increased risk of the variant PROGINS allele and susceptibility for the endometriosis.

Journal of Ovarian Research, 2014

Background/aims: Reported associations of controlled ovarian hyperstimulation response (COH) with... more Background/aims: Reported associations of controlled ovarian hyperstimulation response (COH) with genotypes of the Ser680Asn (N680S) polymorphism in the follicle stimulating hormone receptor (FSHR) gene have conflicting results. Methods: PubMed and Embase databases were searched for studies that investigated the N680S polymorphism in the FSHR gene in COH. Parameters used to examine ovarian response were poor and hyper-responses to COH. Using the meta-analytic approach, we estimated ovarian response risk (odds ratio [OR] with 95% confidence intervals) according to genotype.

Journal of Gastrointestinal Cancer, 2014

Inconsistency of reported associations of the G/A polymorphism (rs2301756) in the PTPN11 gene and... more Inconsistency of reported associations of the G/A polymorphism (rs2301756) in the PTPN11 gene and gastric atrophy prompted us to undertake a meta-analysis. We searched PubMed for published literature up to July 2013. Individual data from studies with case-control design were evaluated for the PTPN11 G/A polymorphism in Helicobacter pylori (-) (seronegative) and (+) (seropositive) subjects (four studies each, totaling 3,597 cases and 4,865 controls). Associations of PTPN11 polymorphism with gastric atrophy in H. pylori (-) and (+) subjects are more readily interpreted in the homozygous and recessive models given that the dominant codominant effects skirted null associations. Thus, homozygous and recessive effects indicated reduced risk [odds ratio (OR) 0.92-0.96, p = 0.51-0.74], which is significant among H. pylori (+) subjects (OR 0.66-0.68, p = 0.04-0.05). Confined to the Japanese, reduced risk effects were unaltered in both groups, less protective among seronegative subjects (OR 0.85-0.86, p = 0.71-0.73) than seropositive subjects with significance in the recessive model (OR 0.67, p = 0.05). Sensitivity analysis demonstrated robustness of the seropositive findings, but probably not the seronegative results where homozygous and recessive pooled ORs were altered from protection to increased risk. Evidence of overall and subgroup decreased risks, strong in seropositive subjects, demonstrates protective effects of the PTPN11 G/A polymorphism from gastric atrophy.

Archives of Gynecology and Obstetrics, 2014

The +331G/A progesterone receptor (PgR) gene polymorphism may influence risk of endometrial cance... more The +331G/A progesterone receptor (PgR) gene polymorphism may influence risk of endometrial cancer. However, data from published studies have been controversial. To evaluate whether combined evidence shows an association between this polymorphism and endometrial cancer, we considered all available studies in a meta-analysis. We searched PubMed and EMBASE and identified eight studies representing data for 3,790 cases and 6,458 controls. We estimated risk [odds ratio (OR) and 95 % confidence interval] of these associations, which were non-significant in the entire body of results. Overall effects indicated increased risks, slightly pronounced in the homozygous and recessive models (OR 1.16-1.17, p = 0.57-0.60). These effects were exacerbated when confined to studies in Hardy-Weinberg Equilibrium (OR 1.33-1.36, p = 0.33-0.35) and in the underpowered subgroup (OR 1.62-1.68, p = 0.27-0.30). The exception is the powered subgroup which showed reduced risk (OR 0.96-0.97, p = 0.92-0.93). None of the comparisons were heterogeneous, in fact, 10 of the 16 comparisons had zero heterogeneity (I (2) = 0 %). In summary, the non-significant results suggest that the PgR +331G/A polymorphism might not be a conspicuous low-penetrant risk factor for developing endometrial cancer.

Epidemiological studies have suggested an association between selenium intake and protection from... more Epidemiological studies have suggested an association between selenium intake and protection from a variety of cancer. Considering this clinical importance of selenium, we aimed to identify the genes associated with resistance to selenium treatment. We have applied a previous methodology developed by our group, which is based on the genetic and pharmacological data publicly available for the NCI60 cancer cell line panel. In short, we have categorized the NCI60 cell lines as selenium resistant and sensitive based on their growth inhibition (GI50) data. Then, we have utilized the Affymetrix 125K SNP chip data available and carried out a genome-wide case-control association study for the selenium sensitive and resistant NCI60 cell lines. Our results showed statistically significant association of four SNPs in 5q33-34, 10q11.2, 10q22.3 and 14q13.1 with selenium resistance. These SNPs were located in introns of the genes encoding for a kinase-scaffolding protein (AKAP6), a membrane protein (SGCD), a channel protein (KCNMA1), and a protein kinase (PRKG1). The knock-down of KCNMA1 by siRNA showed increased sensitivity to selenium in both LNCaP and PC3 cell lines. Furthermore, SNP-SNP interaction (epistasis) analysis indicated the interactions of the SNPs in AKAP6 with SGCD as well as SNPs in AKAP6 with KCNMA1 with each other, assuming additive genetic model. These genes were also all involved in the Ca 2+ signaling, which has a direct role in induction of apoptosis and induction of apoptosis in tumor cells is consistent with the chemopreventive action of selenium. Once our findings are further validated, this knowledge can be translated into clinics where individuals who can benefit from the chemopreventive characteristics of the selenium supplementation will be easily identified using a simple DNA analysis.

BMC Genetics, 2014

Background: There is growing evidence that the ghrelin axis, including ghrelin (GHRL) and its rec... more Background: There is growing evidence that the ghrelin axis, including ghrelin (GHRL) and its receptor, the growth hormone secretagogue receptor (GHSR), play a role in cancer progression. Ghrelin gene and ghrelin receptor gene polymorphisms have been reported to have a range of effects in cancer, from increased risk, to protection from cancer, or having no association. In this study we aimed to clarify the role of ghrelin and ghrelin receptor polymorphisms in cancer by performing a meta-analysis of published case-control studies. We conducted searches of the literature published up to January 2013 in MEDLINE using the PubMed search engine. Individual data on 8,430 cases and 14,008 controls from six case-control studies of an all Caucasian population were evaluated for three ghrelin gene (GHRL; rs696217, rs4684677, rs2075356) and one ghrelin receptor (GHSR; rs572169) polymorphism in breast cancer, esophageal cancer, colorectal cancer and non-Hodgkins lymphoma. Results: In the overall analysis, homozygous and recessive associations indicated that the minor alleles of rs696217 and rs2075356 GHRL polymorphisms conferred reduced cancer risk (odds ratio [OR] 0.61-0.78). The risk was unchanged for breast cancer patients when analysed separately (OR 0.73-0.83). In contrast, the rs4684677 GHRL and the rs572169 GHSR polymorphisms conferred increased breast cancer risk (OR 1.97-1.98, p = 0.08 and OR 1.42-1.43, p = 0.08, respectively). All dominant and co-dominant effects showed null effects (OR 0.96-1.05), except for the rs572169 co-dominant effect, with borderline increased risk (OR 1.08, p = 0.05).

Proteins: Structure, Function, and Bioinformatics, 2007

Proteins destined for secretion or membrane compartments possess signal peptides for insertion in... more Proteins destined for secretion or membrane compartments possess signal peptides for insertion into the membrane. The signal peptide is therefore critical for localization and function of cell surface receptors and ligands that mediate cell-cell communication. About 4% of all human proteins listed in UniProt database have signal peptide domains in their N terminals. A comprehensive literature survey was performed to retrieve functional and disease associated genetic variants in the signal peptide domains of human proteins. In 21 human proteins we have identified 26 disease associated mutations within their signal peptide domains, 14 mutations of which have been experimentally shown to impair the signal peptide function and thus influence protein transportation. We took advantage of SignalP 3.0 predictions to characterize the signal peptide prediction score differences between the mutant and the wild-type alleles of each mutation, as well as 189 previously uncharacterized single nucleotide polymorphisms (SNPs) found to be located in the signal peptide domains of 165 human proteins. Comparisons of signal peptide prediction outcomes of mutations and SNPs, have implicated SNPs potentially impacting the signal peptide function, and thus the cellular localization of the human proteins. The majority of the top candidate proteins represented membrane and secreted proteins that are associated with molecular transport, cell signaling and cell to cell interaction processes of the cell. This is the first study that systematically characterizes genetic variation occurring in the signal peptides of all human proteins. This study represents a useful strategy for prioritization of SNPs occurring within the signal peptide domains of human proteins. Functional evaluation of candidates identified herein may reveal effects on major cellular processes including immune cell function, cell recognition and adhesion, and signal transduction.

Journal of Gastrointestinal Cancer, 2014

Reported associations of capsaicin with gastric cancer development have been conflicting. Here, w... more Reported associations of capsaicin with gastric cancer development have been conflicting. Here, we examine 10 published articles that explore these associations using 2,452 cases and 3,996 controls. We used multiple search strategies in MEDLINE through PubMed to seek for suitable articles that had case-control design with gastric cancer as outcome. The outcomes of our study shows protection (odds ratio [OR] 0.55, P = 0.003) and susceptibility (OR 1.94, P = 0.0004), both significant with low and medium-high intake of capsaicin, respectively, although under relatively heterogeneous conditions (P(heterogeneity) = <0.0001). Outlier analysis resulted in loss of overall heterogeneity (P = 0.14) without affecting the pooled ORs. Among the subgroups, low intake elicited protection in both Korean (OR 0.37) and Mexican (OR 0.63) populations while high intake rendered these subgroups susceptible (OR 2.96 and OR 1.57, respectively). These subgroup values were highly significant (P = 0.0001-0.01) obtained in heterogeneous conditions (P(heterogeneity) < 0.0001-0.04). The homogeneous (P(heterogeneity) = 0.27-0.37) H. pylori (OR 0.60 and 1.69) effects were highly significant (P < 0.001) in the low and medium-high intake analyses, respectively. Given outcomes from the tests of interaction, high capsaicin intake is significantly different from the protection that low consumption offers. This meta-analysis implies moderation in capsaicin consumption in order to derive its protective benefits.

Indian Journal of Medical Microbiology, 2014

The use of meta-analysis in microbiology may facilitate decision-making that impacts public healt... more The use of meta-analysis in microbiology may facilitate decision-making that impacts public health policy. Directed at clinicians and researchers in microbiology, this review outlines the steps in performing this statistical technique, addresses its biases and describes its value in this discipline. The survey to estimate extent of the use of meta-analyses in microbiology shows the remarkable growth in the use of this research methodology, from a minimal Asian output to a level comparable with those of Europe and North America in the last 7 years.

Proceedings of the National Academy of Sciences, 2000

Haplotypes constructed from Y-chromosome markers were used to trace the paternal origins of the J... more Haplotypes constructed from Y-chromosome markers were used to trace the paternal origins of the Jewish Diaspora. A set of 18 biallelic polymorphisms was genotyped in 1,371 males from 29 populations, including 7 Jewish (Ashkenazi, Roman, North African, Kurdish, Near Eastern, Yemenite, and Ethiopian) and 16 non-Jewish groups from similar geographic locations. The Jewish populations were characterized by a diverse set of 13 haplotypes that were also present in non-Jewish populations from Africa, Asia, and Europe. A series of analyses was performed to address whether modern Jewish Y-chromosome diversity derives mainly from a common Middle Eastern source population or from admixture with neighboring non-Jewish populations during and after the Diaspora. Despite their long-term residence in different countries and isolation from one another, most Jewish populations were not significantly different from one another at the genetic level.

Environmental Science & Technology, 2012

An ecosystem perspective to restoring beneficial uses in Areas of Concern can be interpreted as a... more An ecosystem perspective to restoring beneficial uses in Areas of Concern can be interpreted as a shift from the traditional elucidation of simple cause−effect relationships to a multicausal way of thinking that more effectively accommodates ecosystem complexity. This holistic management paradigm has also pervaded the contemporary ecological modeling practice, making compelling the adoption of more sophisticated ecosystem modeling tools. In this study, our primary objective is to develop a Bayesian hierarchical network of simple ecological models for Lake Simcoe, Ontario, Canada, aiming to establish a realistic representation of the causal connections among exogenous nutrient loading, ambient nutrient conditions, and epilimnetic plankton dynamics. In particular, we used a spatially explicit simple mass-balance model forced with idealized sinusoidal loading to predict total phosphorus concentrations. A structural equation model was then used to delineate the interplay among nutrients, ambient light conditions, phytoplankton, and herbivorous biomass. Our analysis highlights the strength of the causal linkages between total phosphorus and water clarity with phytoplankton as well as the capacity of zooplankton grazing to modulate the algal standing crop. Our Bayesian network is also used to examine the exceedance frequency of threshold values for total phosphorus (15 μg/L) and chlorophyll a (4 μg/L) concentrations under scenarios of phosphorus loading reduction. Our study suggests that a 15% phosphorus loading decrease will still result in >25% violations of the 4 μg chla/L value in the two embayments of Lake Simcoe (Cook's Bay and Kempenfelt Bay). The TP levels will decrease in response to the exogenous loading reductions and this improvement will be primarily manifested in the northcentral segments of the system.

Journal of Great Lakes Research, 2011

Climate change is anticipated to have major physical and biological effects on aquatic ecosystems... more Climate change is anticipated to have major physical and biological effects on aquatic ecosystems. Changes to the thermal regime of lakes such as shorter duration of ice-cover, earlier onset of stratification and an increase in the length of the stratified period have already been observed in some lakes in North America and Europe. Using vertical temperature profiles of Lake Simcoe during the open-water period from 1980 to 2008 we evaluated trends in water column stability, the onset of stratification and the timing of fall turnover at three stations situated in the lake's two bays and its main basin. Dramatic changes were observed at the three stations; each stratified earlier in the spring, mixed later in the fall and remained stratified for more than a month longer in 2008 compared to 1980. Long-term monotonic trends in the timing of the onset of thermal stratification, fall mixing and duration of stratification were significant. These trends resulted from changes in water column density that are strongly correlated with increasing average air temperatures over time, indicating that climate warming has had a significant effect on the thermal regime of Lake Simcoe.

We present a Bayesian variable selection procedure that is applicable to genomewide studies invol... more We present a Bayesian variable selection procedure that is applicable to genomewide studies involving a combination of clinical, gene expression and genotype information. We use the Mode Oriented Stochastic Search (MOSS) algorithm of Dobra and Massam (2010) to explore regions of high posterior probability for regression models involving discrete covariates and to perform hierarchical log-linear model search to identify the most relevant associations among the resulting subsets of regressors. We illustrate our methodology with simulated data, expression data and SNP data.

Annals of Human Biology, 2014

The geographical location of Egypt at the crossroads of several major cultural areas between Nort... more The geographical location of Egypt at the crossroads of several major cultural areas between North Africa and the Middle East has contributed to its population history. To analyse the genetic structure of the population living in two geographical parts of Egypt. A sample of 112 Egyptians from the North African part of Egypt (Ismailia sample) and a sample of 52 Egyptians from the Asian part Sinai, have been analysed using 10 Alu insertion polymorphisms. The results of the present study showed a significant genetic difference between the Sinai and Ismailia samples. The latter showed an evident genetic affinity with North African populations; whereas the Sinai sample was found to be genetically closer to the Middle East populations. The Sinai sample showed a low average heterozygosity, unlike that found in the Ismailia sample. This study provides new insights into the genetic structure of the Egyptian population living in a land bridge between Africa and Asia. Results suggest a genetic discontinuity between the Sinai population and that of the North African part of Egypt. This discontinuity would have been maintained thanks to geo-climatic and social factors.

Inland Waters, 2013

Thermophilic Campylobacter species have been implicated in human gastrointestinal infections and ... more Thermophilic Campylobacter species have been implicated in human gastrointestinal infections and can occur in agricultural run off, sewage discharges, and the feces of domestic and wild animals including birds. A 2-year study was designed to investigate the occurrence of the primary thermophilic Campylobacter species (C. jejuni, coli, and lari) associated with human disease at 5 recreational beaches on Lake Simcoe, Ontario, Canada. A biweekly sampling program involved collecting water samples across 3 depth zones (sand pore water and ankle-and chest-depth waters). To identify the potential sources of contamination, samples were also collected from 4 neighboring rivers corresponding to selected beaches, a few fresh seagull and Canada geese fecal droppings on beaches, and a stormwater outfall. Water and fecal samples were processed for Campylobacter spp. isolation and detection using a minimum probable number culture enrichment protocol. Thermophilic Campylobacter spp. generally occurred infrequently and at low concentrations (≤30 cells L −1 ) at all sampling locations; they were detected in 12% of water samples from beaches (n = 289) compared to 14% from rivers (n = 100). C. jejuni and C. lari were the species most commonly detected. Nine isolates identified as unknown Campylobacter spp. were further sequenced and shown to be more closely related to Arcobacter spp. At beaches, thermophilic Campylobacter spp. were generally detected more often in sand pore water than in ankle-or chest-depth water. The study suggests that sand, rivers, and bird droppings could be potential sources of Campylobacter spp. contamination at Lake Simcoe recreational beaches.

Biomarkers in Cancer, 2015

Inconsistency in the reported associations between the A66G polymorphism in the methionine syntha... more Inconsistency in the reported associations between the A66G polymorphism in the methionine synthase reductase (MTRR) gene and colorectal cancer (CRC) prompted a meta-analysis, so that we could obtain a more precise estimate. Databases searches of the published literature yielded 20 case-control studies from 17 articles (8,371 cases and 12,574 controls). We calculated pooled odds ratios (ORs) and 95% confidence intervals in three genetic comparisons (A allele, G allele, and A/G genotype). We found no evidence of overall associations between MTRR A66G and CRC risk (OR 0.96-1.05, P = 0.12-0.44). This was materially unchanged when reanalyzed without the Hardy-Weinberg equilibrium (HWE)-deviating studies (OR 0.97-1.06, P = 0.11-0.65). In the A allele comparison, however, outlier treatment generated significant protection (OR 0.91, P = 0.01). Combined removal of the outliers and HWE-deviating studies reflected this summary effect (OR 0.90, P = 0.01) as did the pooled OR from high-quality studies (OR 0.90, P = 0.01). Only the Asian subgroup showed significant (both at P = 0.05) A allele (OR 1.13) and A/G genotype (OR 0.88) associations. In conclusion, post-outlier A allele effects were protective. Our study also suggests ethnic-specific associations with Asian susceptibility and protection in the A allele and A/G genotype comparisons, respectively. Folate status showed no association of this polymorphism with CRC.

Journal of Gastrointestinal Cancer, 2015

Reported associations of ACE polymorphisms with gastric cancer have been inconsistent, prompting ... more Reported associations of ACE polymorphisms with gastric cancer have been inconsistent, prompting a meta-analysis of 12 published case-control studies where we estimated risk (odds ratio [OR]). We searched MEDLINE through PubMed and EMBASE for suitable articles that had case-control design with gastric cancer as outcome. In this meta-analysis, our overall findings were subjected to modifier analyses (outlier and sensitivity treatments). We also performed subgroup analysis based on ethnicity (German and Japanese) and histological subtype (intestinal and diffuse). Significance of the protective effects among homozygote carriers of the II genotype (OR 0.54-0.63, P = 0.01-0.02) disappeared with outlier analysis (OR 0.81-0.88, P = 0.12-0.14). Among DD homozygotes, this treatment altered the direction of association from weak protection (OR 0.95-0.96, P = 0.79-0.82) to increased risk (OR 1.13-1.19, P = 0.14-0.16). No significant associations were observed among ID genotype carriers (OR 0.91-0.94, P = 0.69-0.72). Japanese pooled effects varied across the genotype comparisons (OR 0.93-1.06, P = 0.54-0.72). Sensitivity treatment demonstrated robustness of the II genotype, but not the other two, both in overall and subgroup analyses. Histological subtype analysis yielded protection from intestinal cancer across the comparisons (OR 0.38-0.71, P = 0.15-0.50) but variable results for the diffuse type (OR 0.59-1.32, P = 0.19-0.92). In summary, carriers of the ACE II genotype appear to be protected from gastric cancer, regardless of ethnicity or tumor type.

Human genomics, 2006

Although highly penetrant alleles of BRCA1 and BRCA2 have been shown to predispose to breast canc... more Although highly penetrant alleles of BRCA1 and BRCA2 have been shown to predispose to breast cancer, the majority of breast cancer cases are assumed to result from the presence of low-moderate penetrant alleles and environmental carcinogens. Non-synonymous single nucleotide polymorphisms (nsSNPs) are hypothesised to contribute to disease susceptibility and approximately 30 per cent of them are predicted to have a biological significance. In this study, we have applied a bioinformatics-based strategy to identify breast cancer-related nsSNPs from 981 carcinogenesis-related genes expressed in breast tissue. Our results revealed a total of 367 validated nsSNPs, 109 (29.7 per cent) of which are predicted to affect the protein function (functional nsSNPs), suggesting that these nsSNPs are likely to influence the development and homeostasis of breast tissue and hence contribute to breast cancer susceptibility. Sixty-seven of the functional nsSNPs presented as commonly occurring nsSNPs (min...

BioTechniques, 2002

... 2002 May;32(5):1006, 1008, 1010. Modified rapid expansion detection method to analyze Cag/CTG... more ... 2002 May;32(5):1006, 1008, 1010. Modified rapid expansion detection method to analyze Cag/CTG repeat expansions. Jarjanazi H, Ozcelik H. Mount Sinai Hospital, Toronto, Ontario, Canada. PMID: 12019772 [PubMed - indexed for MEDLINE]. Publication Types: ...

Archives of Gynecology and Obstetrics, 2014

Reported associations of progesterone receptor gene polymorphism (PROGINS) with endometriosis hav... more Reported associations of progesterone receptor gene polymorphism (PROGINS) with endometriosis have been inconsistent. To evaluate the association between the PROGINS polymorphism and the risk of endometriosis. A meta-analysis of 12 published case-control studies with a total sample size of 3,321 (1,323 cases/1,998 controls) was performed. We estimated the risk (odds ratio [OR] 95 % confidence intervals) of endometriosis association with the PROGINS polymorphism. An association between the presence of the variant allele and risk of endometriosis was found, more in the homozygous and recessive models (OR 1.41-1.43, p = 0.15-0.17), and less in the dominant and co-dominant models (OR 1.22, p = 0.11-0.15). Reanalysis without the studies whose controls deviated from the Hardy-Weinberg Equilibrium did not materially alter the dominant and co-dominant effects (OR 1.19-1.22, p = 0.19-0.32), but exacerbated the homozygous and recessive effects (OR 1.59, p = 0.09). The subgroups based on geography showed increased risk associations, consistently significant in the European (OR 1.52-2.72, p = 0.0008-0.03) but not in the Brazilian studies, where ORs ranged from reduced (OR 0.70-0.74, p = 0.54-0.61) to increased (OR 1.11, p = 0.75) risks. Heterogeneity was confined in all comparisons to the dominant and co-dominant models (I (2) = 38-70 %), except in the European subgroup, which had zero heterogeneity (I (2) = 0 %) in all genetic models, as did all homozygous and recessive effects. This meta-analysis provides a comprehensive profile of the role of the PROGINS polymorphism in endometriosis by exploring the magnitude of the summary effects with modifier analysis. This magnitude is expressed with modulation or exacerbation of the summary effects, as defined by the parameters of the analysis. Thus, the results showed trend towards an increased risk of the variant PROGINS allele and susceptibility for the endometriosis.

Journal of Ovarian Research, 2014

Background/aims: Reported associations of controlled ovarian hyperstimulation response (COH) with... more Background/aims: Reported associations of controlled ovarian hyperstimulation response (COH) with genotypes of the Ser680Asn (N680S) polymorphism in the follicle stimulating hormone receptor (FSHR) gene have conflicting results. Methods: PubMed and Embase databases were searched for studies that investigated the N680S polymorphism in the FSHR gene in COH. Parameters used to examine ovarian response were poor and hyper-responses to COH. Using the meta-analytic approach, we estimated ovarian response risk (odds ratio [OR] with 95% confidence intervals) according to genotype.

Journal of Gastrointestinal Cancer, 2014

Inconsistency of reported associations of the G/A polymorphism (rs2301756) in the PTPN11 gene and... more Inconsistency of reported associations of the G/A polymorphism (rs2301756) in the PTPN11 gene and gastric atrophy prompted us to undertake a meta-analysis. We searched PubMed for published literature up to July 2013. Individual data from studies with case-control design were evaluated for the PTPN11 G/A polymorphism in Helicobacter pylori (-) (seronegative) and (+) (seropositive) subjects (four studies each, totaling 3,597 cases and 4,865 controls). Associations of PTPN11 polymorphism with gastric atrophy in H. pylori (-) and (+) subjects are more readily interpreted in the homozygous and recessive models given that the dominant codominant effects skirted null associations. Thus, homozygous and recessive effects indicated reduced risk [odds ratio (OR) 0.92-0.96, p = 0.51-0.74], which is significant among H. pylori (+) subjects (OR 0.66-0.68, p = 0.04-0.05). Confined to the Japanese, reduced risk effects were unaltered in both groups, less protective among seronegative subjects (OR 0.85-0.86, p = 0.71-0.73) than seropositive subjects with significance in the recessive model (OR 0.67, p = 0.05). Sensitivity analysis demonstrated robustness of the seropositive findings, but probably not the seronegative results where homozygous and recessive pooled ORs were altered from protection to increased risk. Evidence of overall and subgroup decreased risks, strong in seropositive subjects, demonstrates protective effects of the PTPN11 G/A polymorphism from gastric atrophy.

Archives of Gynecology and Obstetrics, 2014

The +331G/A progesterone receptor (PgR) gene polymorphism may influence risk of endometrial cance... more The +331G/A progesterone receptor (PgR) gene polymorphism may influence risk of endometrial cancer. However, data from published studies have been controversial. To evaluate whether combined evidence shows an association between this polymorphism and endometrial cancer, we considered all available studies in a meta-analysis. We searched PubMed and EMBASE and identified eight studies representing data for 3,790 cases and 6,458 controls. We estimated risk [odds ratio (OR) and 95 % confidence interval] of these associations, which were non-significant in the entire body of results. Overall effects indicated increased risks, slightly pronounced in the homozygous and recessive models (OR 1.16-1.17, p = 0.57-0.60). These effects were exacerbated when confined to studies in Hardy-Weinberg Equilibrium (OR 1.33-1.36, p = 0.33-0.35) and in the underpowered subgroup (OR 1.62-1.68, p = 0.27-0.30). The exception is the powered subgroup which showed reduced risk (OR 0.96-0.97, p = 0.92-0.93). None of the comparisons were heterogeneous, in fact, 10 of the 16 comparisons had zero heterogeneity (I (2) = 0 %). In summary, the non-significant results suggest that the PgR +331G/A polymorphism might not be a conspicuous low-penetrant risk factor for developing endometrial cancer.

Epidemiological studies have suggested an association between selenium intake and protection from... more Epidemiological studies have suggested an association between selenium intake and protection from a variety of cancer. Considering this clinical importance of selenium, we aimed to identify the genes associated with resistance to selenium treatment. We have applied a previous methodology developed by our group, which is based on the genetic and pharmacological data publicly available for the NCI60 cancer cell line panel. In short, we have categorized the NCI60 cell lines as selenium resistant and sensitive based on their growth inhibition (GI50) data. Then, we have utilized the Affymetrix 125K SNP chip data available and carried out a genome-wide case-control association study for the selenium sensitive and resistant NCI60 cell lines. Our results showed statistically significant association of four SNPs in 5q33-34, 10q11.2, 10q22.3 and 14q13.1 with selenium resistance. These SNPs were located in introns of the genes encoding for a kinase-scaffolding protein (AKAP6), a membrane protein (SGCD), a channel protein (KCNMA1), and a protein kinase (PRKG1). The knock-down of KCNMA1 by siRNA showed increased sensitivity to selenium in both LNCaP and PC3 cell lines. Furthermore, SNP-SNP interaction (epistasis) analysis indicated the interactions of the SNPs in AKAP6 with SGCD as well as SNPs in AKAP6 with KCNMA1 with each other, assuming additive genetic model. These genes were also all involved in the Ca 2+ signaling, which has a direct role in induction of apoptosis and induction of apoptosis in tumor cells is consistent with the chemopreventive action of selenium. Once our findings are further validated, this knowledge can be translated into clinics where individuals who can benefit from the chemopreventive characteristics of the selenium supplementation will be easily identified using a simple DNA analysis.

BMC Genetics, 2014

Background: There is growing evidence that the ghrelin axis, including ghrelin (GHRL) and its rec... more Background: There is growing evidence that the ghrelin axis, including ghrelin (GHRL) and its receptor, the growth hormone secretagogue receptor (GHSR), play a role in cancer progression. Ghrelin gene and ghrelin receptor gene polymorphisms have been reported to have a range of effects in cancer, from increased risk, to protection from cancer, or having no association. In this study we aimed to clarify the role of ghrelin and ghrelin receptor polymorphisms in cancer by performing a meta-analysis of published case-control studies. We conducted searches of the literature published up to January 2013 in MEDLINE using the PubMed search engine. Individual data on 8,430 cases and 14,008 controls from six case-control studies of an all Caucasian population were evaluated for three ghrelin gene (GHRL; rs696217, rs4684677, rs2075356) and one ghrelin receptor (GHSR; rs572169) polymorphism in breast cancer, esophageal cancer, colorectal cancer and non-Hodgkins lymphoma. Results: In the overall analysis, homozygous and recessive associations indicated that the minor alleles of rs696217 and rs2075356 GHRL polymorphisms conferred reduced cancer risk (odds ratio [OR] 0.61-0.78). The risk was unchanged for breast cancer patients when analysed separately (OR 0.73-0.83). In contrast, the rs4684677 GHRL and the rs572169 GHSR polymorphisms conferred increased breast cancer risk (OR 1.97-1.98, p = 0.08 and OR 1.42-1.43, p = 0.08, respectively). All dominant and co-dominant effects showed null effects (OR 0.96-1.05), except for the rs572169 co-dominant effect, with borderline increased risk (OR 1.08, p = 0.05).

Proteins: Structure, Function, and Bioinformatics, 2007

Proteins destined for secretion or membrane compartments possess signal peptides for insertion in... more Proteins destined for secretion or membrane compartments possess signal peptides for insertion into the membrane. The signal peptide is therefore critical for localization and function of cell surface receptors and ligands that mediate cell-cell communication. About 4% of all human proteins listed in UniProt database have signal peptide domains in their N terminals. A comprehensive literature survey was performed to retrieve functional and disease associated genetic variants in the signal peptide domains of human proteins. In 21 human proteins we have identified 26 disease associated mutations within their signal peptide domains, 14 mutations of which have been experimentally shown to impair the signal peptide function and thus influence protein transportation. We took advantage of SignalP 3.0 predictions to characterize the signal peptide prediction score differences between the mutant and the wild-type alleles of each mutation, as well as 189 previously uncharacterized single nucleotide polymorphisms (SNPs) found to be located in the signal peptide domains of 165 human proteins. Comparisons of signal peptide prediction outcomes of mutations and SNPs, have implicated SNPs potentially impacting the signal peptide function, and thus the cellular localization of the human proteins. The majority of the top candidate proteins represented membrane and secreted proteins that are associated with molecular transport, cell signaling and cell to cell interaction processes of the cell. This is the first study that systematically characterizes genetic variation occurring in the signal peptides of all human proteins. This study represents a useful strategy for prioritization of SNPs occurring within the signal peptide domains of human proteins. Functional evaluation of candidates identified herein may reveal effects on major cellular processes including immune cell function, cell recognition and adhesion, and signal transduction.

Journal of Gastrointestinal Cancer, 2014

Reported associations of capsaicin with gastric cancer development have been conflicting. Here, w... more Reported associations of capsaicin with gastric cancer development have been conflicting. Here, we examine 10 published articles that explore these associations using 2,452 cases and 3,996 controls. We used multiple search strategies in MEDLINE through PubMed to seek for suitable articles that had case-control design with gastric cancer as outcome. The outcomes of our study shows protection (odds ratio [OR] 0.55, P = 0.003) and susceptibility (OR 1.94, P = 0.0004), both significant with low and medium-high intake of capsaicin, respectively, although under relatively heterogeneous conditions (P(heterogeneity) = <0.0001). Outlier analysis resulted in loss of overall heterogeneity (P = 0.14) without affecting the pooled ORs. Among the subgroups, low intake elicited protection in both Korean (OR 0.37) and Mexican (OR 0.63) populations while high intake rendered these subgroups susceptible (OR 2.96 and OR 1.57, respectively). These subgroup values were highly significant (P = 0.0001-0.01) obtained in heterogeneous conditions (P(heterogeneity) < 0.0001-0.04). The homogeneous (P(heterogeneity) = 0.27-0.37) H. pylori (OR 0.60 and 1.69) effects were highly significant (P < 0.001) in the low and medium-high intake analyses, respectively. Given outcomes from the tests of interaction, high capsaicin intake is significantly different from the protection that low consumption offers. This meta-analysis implies moderation in capsaicin consumption in order to derive its protective benefits.

Indian Journal of Medical Microbiology, 2014

The use of meta-analysis in microbiology may facilitate decision-making that impacts public healt... more The use of meta-analysis in microbiology may facilitate decision-making that impacts public health policy. Directed at clinicians and researchers in microbiology, this review outlines the steps in performing this statistical technique, addresses its biases and describes its value in this discipline. The survey to estimate extent of the use of meta-analyses in microbiology shows the remarkable growth in the use of this research methodology, from a minimal Asian output to a level comparable with those of Europe and North America in the last 7 years.

Proceedings of the National Academy of Sciences, 2000

Haplotypes constructed from Y-chromosome markers were used to trace the paternal origins of the J... more Haplotypes constructed from Y-chromosome markers were used to trace the paternal origins of the Jewish Diaspora. A set of 18 biallelic polymorphisms was genotyped in 1,371 males from 29 populations, including 7 Jewish (Ashkenazi, Roman, North African, Kurdish, Near Eastern, Yemenite, and Ethiopian) and 16 non-Jewish groups from similar geographic locations. The Jewish populations were characterized by a diverse set of 13 haplotypes that were also present in non-Jewish populations from Africa, Asia, and Europe. A series of analyses was performed to address whether modern Jewish Y-chromosome diversity derives mainly from a common Middle Eastern source population or from admixture with neighboring non-Jewish populations during and after the Diaspora. Despite their long-term residence in different countries and isolation from one another, most Jewish populations were not significantly different from one another at the genetic level.