Human Papillomavirus Type 16 Genetic Variants: Phylogeny and Classification Based on E6 and LCR

Naturally occurring genetic variants of human papillomavirus type 16 (HPV16) are common and have previously been classified into 4 major lineages; European-Asian (EAS), including the sublineages European (EUR) and Asian (As), African 1 (AFR1), African 2 (AFR2), and North-American/Asian-American (NA/AA). We aimed to improve the classification of HPV16 variant lineages by using a large resource of HPV16-positive cervical samples collected from geographically diverse populations in studies on HPV and/or cervical cancer undertaken by the International Agency for Research on Cancer. In total, we sequenced the entire E6 genes and long control regions (LCRs) of 953 HPV16 isolates from 27 different countries worldwide. Phylogenetic analyses confirmed previously described variant lineages and subclassifications. We characterized two new sublineages within each of the lineages AFR1 and AFR2 that are robustly classified using E6 and/or the LCR. We could differentiate previously identified AA1, AA2, and NA sublineages, although they could not be distinguished by E6 alone, requiring the LCR for correct phylogenetic classification. We thus provide a classification system for HPV16 genomes based on 13 and 32 phylogenetically distinguishing positions in E6 and the LCR, respectively, that distinguish nine HPV16 variant sublineages (EUR, As, AFR1a, AFR1b, AFR2a, AFR2b, NA, AA1, and AA2). Ninety-seven percent of all 953 samples fitted this classification perfectly. Other positions were frequently polymorphic within one or more lineages but did not define phylogenetic subgroups. Such a standardized classification of HPV16 variants is important for future epidemiological and biological studies of the carcinogenic potential of HPV16 variant lineages

Supplementary Material for: Infrastructure and Facilities for Human Biobanking in Low- and Middle-Income Countries: A Situation Analysis

<b><i>Objective:</i></b> To collect information on biobanking facilities in low- and middle-income countries (LMICs) as a first step towards establishing an LMIC biobank and cohort building network (BCNet) to support research, with a focus on cancer control. <b><i>Method:</i></b> Sixty centres were identified from sources including cancer centres, universities, hospitals, and public health facilities and invited to participate in a survey between December 2012 and March 2013. <b><i>Results:</i></b> Of the 27 centres (45%) that responded, most have existed for <10 years. They store between 1,000 and 1,000,000 research samples as well as samples remaining after clinical diagnosis. Sample storage is mostly in freezers, although 45% (9/20) of the centres do not have regular access to electricity. Biobank managers, sample management systems, and mechanisms for follow-up using linkages are uncommon. Many (80%; 21/26) of the centres have regulations to govern research, but regulations for the use of biobank resources (samples and data) are not well developed. <b><i>Conclusions:</i></b> Biobanking facilities are being developed in LMICs. Shortcomings in international visibility, sample sharing regulations, standardization, quality assurance, and sample management systems could be alleviated by international networking. Stakeholders need to work together to increase access to high-quality biological resources for scientific research

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The extent of linkage disequilibrium in a large cattle population of western Africa and its consequences for association studies

Several previous studies concluded that linkage disequilibrium (LD) in livestock populations from developed countries originated from the impact of strong selection. Here, we assessed the extent of LD in a cattle population from western Africa that was bred in an extensive farming system. The analyses were performed on 363 individuals in a Bos indicus x Bos taurus population using 42 microsatellite markers on BTA04, BTA07 and BTA13. A high level of expected heterozygosity (0.71), a high mean number of alleles per locus (9.7) and a mild shift in Hardy-Weinberg equilibrium were found. Linkage disequilibrium extended over shorter distances than what has been observed in cattle from developed countries. Effective population size was assessed using two methods; both methods produced large values: 1388 when considering heterozygosity (assuming a mutation rate of 10(-3)) and 2344 when considering LD on whole linkage groups (assuming a constant population size over generations). However, analysing the decay of LD as a function of marker spacing indicated a decreasing trend in effective population size over generations. This decrease could be explained by increasing selective pressure and/or by an admixture process. Finally, LD extended over small distances, which suggested that whole-genome scans will require a large number of markers. However, association studies using such populations will be effective

Aberrant DNA methylation of cancer-associated genes in gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Epigenetic events have emerged as key mechanisms in the regulation of critical biological processes and in the development of a wide variety of human malignancies, including gastric cancer (GC), however precise gene targets of aberrant DNA methylation in GC remain largely unknown. Here, we have combined pyrosequencing-based quantitative analysis of DNA methylation in 98 GC cases and 64 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in cancer tissue and non-tumorigenic adjacent tissue of an independent series of GC samples. A panel of 10 cancer-associated genes (CHRNA3, DOK1, MGMT, RASSF1A, p14ARF, CDH1, MLH1, ALDH2, GNMT and MTHFR) and LINE-1 repetitive elements were included in the analysis and their association with clinicopathological characteristics (sex, age at diagnosis, anatomical sub-site, histological sub-type) was examined. Three out of the 10 genes analyzed exhibited a marked hypermethylation, whereas two genes (ALDH2 and MTHFR) showed significant hypomethylation, in gastric tumors. Among differentially methylated genes, we identified new genes (CHRNA3 and DOK1) as targets of aberrant hypermethylation in GC, suggesting that epigenetic deregulation of these genes and their corresponding cellular pathways may promote the development and progression of GC. We also found that global demethylation of tumor cell genomes occurs in GC, consistent with the notion that abnormal hypermethylation of specific genes occurs concomitantly with genome-wide hypomethylation. Age and gender had no significant influence on methylation states, but an association was observed between LINE-1 and MLH1 methylation levels with histological sub-type and anatomical sub-site. This study identifies aberrant methylation patters in specific genes in GC thus providing information that could be exploited as novel biomarkers in clinics and molecular epidemiology of GC. © 2011 Elsevier Ireland Ltd