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Bereir, R E H; Mohamed, Hiba S.; Seielstad, Mark; Hassani, Abbas; Khalil, E. A. G.; Peacock, Christopher; Blackwell, Jenefer M.; Ibrahim, Muntaser E.

doi:10.1023/a:1024486716497

Cited by 18 publications

(7 citation statements)

References 33 publications

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“…Even if the positively selected substitutions are advantageous, it could be randomly lost over time due to the bottleneck effect. By contrast, the neutral substitutions could be easily fixed in small virus population over time by chance [58]. In our study, six codons with observed amino acid substitutions in DENV-1 E gene consensuses were under neutral genetic drift.…”

Section: Resultsmentioning

confidence: 64%

Dengue virus type 1 clade replacement in recurring homotypic outbreaks

et al. 2013

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BackgroundRecurring dengue outbreaks occur in cyclical pattern in most endemic countries. The recurrences of dengue virus (DENV) infection predispose the population to increased risk of contracting the severe forms of dengue. Understanding the DENV evolutionary mechanism underlying the recurring dengue outbreaks has important implications for epidemic prediction and disease control.ResultsWe used a set of viral envelope (E) gene to reconstruct the phylogeny of DENV-1 isolated between the periods of 1987–2011 in Malaysia. Phylogenetic analysis of DENV-1 E gene revealed that genotype I virus clade replacements were associated with the cyclical pattern of major DENV-1 outbreaks in Malaysia. A total of 9 non-conservative amino acid substitutions in the DENV-1 E gene consensus were identified; 4 in domain I, 3 in domain II and 2 in domain III. Selection pressure analyses did not reveal any positively selected codon site within the full length E gene sequences (1485 nt, 495 codons). A total of 183 (mean dN/dS = 0.0413) negatively selected sites were found within the Malaysian isolates; neither positive nor negative selection was noted for the remaining 312 codons. All the viruses were cross-neutralized by the respective patient sera suggesting no strong support for immunological advantage of any of the amino acid substitutions.ConclusionDENV-1 clade replacement is associated with recurrences of major DENV-1 outbreaks in Malaysia. Our findings are consistent with those of other studies that the DENV-1 clade replacement is a stochastic event independent of positive selection.

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Section: Resultsmentioning

confidence: 64%

Dengue virus type 1 clade replacement in recurring homotypic outbreaks

et al. 2013

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“…p53 genotype distributions and allele frequencies of cervical cancer patients were compared with data from a healthy Sudanese control population published in 2003 (17) (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…Also, 36 formalin-fixed paraffin-embedded tissues (PETs) of non-cancerous samples were used as control for the presence of HPV. The control for the p53 study was previously published data of 253 Sudanese individuals from different ethnic groups (17). DNA was extracted from fresh tissues using TRIzol reagent protocol, while DNA from PETs was extracted using the JETQUICK kit (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Contribution of retinoblastoma LOH and the p53 Arg/Pro polymorphism to cervical cancer

2012

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Epidemiological studies indicate that infections by certain types of human papillomaviruses (HPVs) are causally linked to the development of cervical cancer. It is also known that HPV infections alone do not cause progression to cervical cancer, as additional genetic changes such as loss of distinct chromosomal regions, inactivation of tumor-suppressor genes and activation of oncogenes must also occur in order for malignant transformation to take place. In the present study, 78 patients diagnosed with cervical cancer and 36 cervical cancer-free cases (control) were analyzed for high-risk HPV genotypes (16 and 18) by polymerase chain reaction (PCR). Loss of heterozygosity (LOH) of the retinoblastoma gene (Rb) at two polymorphic intronic sites (intron 1 and 17) and the p53 polymorphism in codon 72 were detected by RFLP and allele-specific PCR, respectively. HPV 16 and 18 were found at frequencies of 93.6 and 8.3% in the cervical cancer and control samples, respectively. LOH was detected in 63% of patients in intron 1 and/or intron 17. p53 allele frequency for Arg/Arg was 43.6% (34/78), for Arg/Pro 37.2% (29/78) and for Pro/Pro 19.2% (15/78). The relative risk (RR) of LOH and Arg/Arg alone was 1.7 and 1.1, respectively, while the combined RR for Rb LOH and p53 Arg/Arg was 2.5. The present study showed a significant association of the chromosomal allelic loss of Rb in Sudanese cervical cancer patients, while no such association was observed with other parameters, such as clinical stage and degree of differentiation; hence, it cannot be a determinant of tumor behavior in cervical carcinoma. Although the p53 arginine allele is itself an important risk factor for cervical cancer, the combined risk with LOH of Rb, which appears to be greater, might indicate a possible epistatic effect of the two genes/polymorphisms.

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“…We recently reported a striking risk association between the p53 arginine allele and breast cancer in Sudanese individuals [35], an unusual example of a common polymorphism with a major effect (OR= 13). This polymorphism has a known geographic pattern of a north South cline [36], which brings into consideration the geographical conditioning of the association between EBV and nasopharyngeal carcinoma endemicity, a known EBV associated tumour, around the tropics [37]. …”

Section: Discussionmentioning

confidence: 99%

Epstein Barr virus: a prime candidate of breast cancer aetiology in Sudanese patients

Yahia

Adam

Elgizouli

et al. 2014

Infect Agents Cancer

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Breast cancer is the commonest cancer in Sudanese women. Reported genetic alterations in the form of mutations in tumor suppressors are low in frequencies and could not explain the peculiarities of the diseases including its focal nature. Potential contributors disease aetiology include oncogenic viruses such as Epstein-Barr virus (EBV), an established culprit of nasopharyngeal carcinoma, one of the most frequent cancers in Sudan.In this study, DNA was extracted from malignant tissue samples and healthy tumour-free tissue from the same breast. Polymerase chain Reaction (PCR) was used to amplify two genes encoding for EBV viral proteins. The presence of Epstein-Barr virus and its cellular localization was confirmed by in situ hybridization (ISH) for Epstein-Barr encoded small RNAs (EBERs). Given the reported low frequency of mutations in BRCA1 and BRCA2 in Sudanese breast cancer patients, the methylation status of six tumor suppressor genes was investigated using methylation specific PCR. EBV genome was detected in 55.5% (n = 90) of breast cancer tissues as compared to 23% in control tissue samples (p = 0.0001). Using ISH, EBV signal was detected in all 18 breast cancer biopsies examined while all five normal breast tissue biopsies tested were negative for EBV. Of six tumour suppressor genes investigated BRCA1, BRCA2, and p14 appeared to be under strong epigenetic silencing.In conclusion, we present evidence of a strong association between EBV and breast carcinoma in Sudanese patients, and considerable epigenetic silencing of tumor suppressors that may likely be an outcome or an association with viral oncogenesis.

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Cited by 18 publications

References 33 publications

Dengue virus type 1 clade replacement in recurring homotypic outbreaks

Dengue virus type 1 clade replacement in recurring homotypic outbreaks

Contribution of retinoblastoma LOH and the p53 Arg/Pro polymorphism to cervical cancer

Epstein Barr virus: a prime candidate of breast cancer aetiology in Sudanese patients

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