Human papilloma viruses and cervical tumours: mapping of integration sites and analysis of adjacent cellular sequences

BACKGROUND: In cervical tumours the integration of human papilloma viruses (HPV) transcripts often results in the generation of transcripts that consist of hybrids of viral and cellular sequences. Mapping data using a variety of techniques has demonstrated that HPV integration occurred without obvious specificity into human genome. However, these techniques could not demonstrate whether integration resulted in the generation of transcripts encoding viral or viral-cellular sequences. The aim of this work was to map the integration sites of HPV DNA and to analyse the adjacent cellular sequences. METHODS: Amplification of the INTs was done by the APOT technique. The APOT products were sequenced according to standard protocols. The analysis of the sequences was performed using BLASTN program and public databases. To localise the INTs PCR-based screening of GeneBridge4-RH-panel was used. RESULTS: Twelve cellular sequences adjacent to integrated HPV16 (INT markers) expressed in squamous cell cervical carcinomas were isolated. For 11 INT markers homologous human genomic sequences were readily identified and 9 of these showed significant homologies to known genes/ESTs. Using the known locations of homologous cDNAs and the RH-mapping techniques, mapping studies showed that the INTs are distributed among different human chromosomes for each tumour sample and are located in regions with the high levels of expression. CONCLUSIONS: Integration of HPV genomes occurs into the different human chromosomes but into regions that contain highly transcribed genes. One interpretation of these studies is that integration of HPV occurs into decondensed regions, which are more accessible for integration of foreign DNA

Improving the Nurse-Family Partnership in Community Practice

Evidence-based preventive interventions are rarely final products. They have reached a stage of development that warrant public investment but require additional research and development to strengthen their effects. The Nurse-Family Partnership (NFP), a program of nurse home visiting, is grounded in findings from replicated randomized controlled trials

The Relationship between Oral Squamous Cell Carcinoma and Human Papillomavirus: A Meta-Analysis of a Chinese Population (1994–2011)

Background: Previous studies indicated that oral squamous cell carcinomas (OSCC) might be related to human papilloma virus (HPV) infection. However, up to now, there still lacks a large sample study to analyze the relationship between OSCC in a Chinese population and oral HPV infection. In the present study, we used a meta-analysis to evaluate the relationship of OSCC with HPV infection in a Chinese population. Methods: The reports on HPV and OSCC in a Chinese population published between January, 1994, and September, 2011 were retrieved via CNKI/WANFANG/OVID/MEDLINE databases. According to the inclusion criteria, we selected 18 eligible case-control studies. After testing the heterogeneity of the studies by the Cochran Q test, the meta-analyses for HPV and HPV16 were performed using the fixed effects model. Results: The overall positive rates of HPV and HPV16 in OSCC were 58.0 % (354/610; 95 % confidence interval [CI], 54.1–61.9) and 47.47 % (169/356; 95 % CI: 42.3–52.7), respectively; which were significantly higher than those in normal controls 10.44% (26/249; 95 % CI: 7.2–14.7) and 7.1 % (13/182; 95 % CI: 4.2–11.8). Quantitative meta-analysis revealed that, compared with normal controls, the combined odds ratios of OSCC with HPV or HPV16 infection were 12.7 (95 % CI: 8.0–20.0) and 9.0 (95% CI: 5.1–15.6), respectively. Both Begg’s test and funnel plots revealed that no publication bias was found in this present study (P.0.05)

Assessment of parental contributions to fast- and slow-growing progenies in the sea bream Sparus aurata L. using a new multiplex PCR

Molecular tools to assist breeding programs in the gilthead sea bream (Sparus aurata L.) are scarce. A new multiplex PCR technique (OVIDORPLEX), which amplifies nine known microsatellite markers, was developed in this work. This multiplex system showed a high mean heterozygosity (>0.800) and a high mean number of alleles per marker (>14) when tested in two sea bream broodstocks (A: 40 breeders and B: 38 breeders). We tested this multiplex PCR for inferring parentage in a Spanish hatchery that graded the animals by size as part of their management procedure. The progeny of the broodstock were divided into fast- and slow-growth groups. Parentage studies revealed that this management procedure entailed a global reduction of the breeders' representation in progeny and that breeders' contributions were significantly unequal. Due to this, effective sample sizes fell to N ê¿13-14 for fast- and N ê¿18-24 for slow-growth progeny groups. These results imply a 3 to 4% rate of inbreeding per generation in the fast-growth group, which is more important to hatchery managers than the slow group. Not all the progeny were evaluated in this experiment (due to the discarding steps), and thus it is difficult to know if the phenotypic performance showed by the fast-growing progeny will be heritable. However, there were genetic differences between the differentiated growth progeny groups (fast vs. slow, F ST values=0.016 to 0.023; P<0.01). We also identified breeders with significantly different contributions to the fast- (10 breeders) or to the slow- (15 breeders) growth progeny groups. Our results demonstrated that this new multiplex PCR could be useful for quantitative programs (breeding programs, detection of QTL, inbreeding control or reconstruction of fish genealogies) to improve the aquaculture of the gilthead sea bream (S. aurata). © 2011 Elsevier B.V.This work was carried out in collaboration with the fish farm Granja Marina Safor, S.L. (Gandia, Valencia, Spain) and the hatchery Piscicultura Marina Mediterranea, S.L. (Burriana, Castellon, Spain). It was financed by JACUMAR (the PROGENSA project) and the Spanish Ministry of Science and Innovation (MICINN; National Program of Resources and Food and Agriculture Technologies, AGL2006-13411-C03-00, SELECTSPARUS, and AGL2007-64040-C03-00, SELECTBREAM, including European Regional Development Funds). V. Gallego was supported by a FPI scholarship financed by MICINN; C. Garcia-Fernandez was supported by a FPU scholarship financed by MICINN; and I. Mazzeo was supported by a FPI scholarship financed by Generalitat Valenciana. We are indebted to three anonymous referees and the journal editor for valuable comments.Borrell, YJ.; Gallego Albiach, V.; García Fernández, C.; Mazzeo ., I.; Pérez Igualada, LM.; Asturiano Nemesio, JF.; Carleos, CE.... (2011). Assessment of parental contributions to fast- and slow-growing progenies in the sea bream Sparus aurata L. using a new multiplex PCR. Aquaculture. 314(1-4):58-65. https://doi.org/10.1016/j.aquaculture.2011.01.028S58653141-

Microarray comparative genomic hybridization detection of chromosomal imbalances in uterine cervix carcinoma

BACKGROUND: Chromosomal Comparative Genomic Hybridization (CGH) has been applied to all stages of cervical carcinoma progression, defining a specific pattern of chromosomal imbalances in this tumor. However, given its limited spatial resolution, chromosomal CGH has offered only general information regarding the possible genetic targets of DNA copy number changes. METHODS: In order to further define specific DNA copy number changes in cervical cancer, we analyzed 20 cervical samples (3 pre-malignant lesions, 10 invasive tumors, and 7 cell lines), using the GenoSensor microarray CGH system to define particular genetic targets that suffer copy number changes. RESULTS: The most common DNA gains detected by array CGH in the invasive samples were located at the RBP1-RBP2 (3q21-q22) genes, the sub-telomeric clone C84C11/T3 (5ptel), D5S23 (5p15.2) and the DAB2 gene (5p13) in 58.8% of the samples. The most common losses were found at the FHIT gene (3p14.2) in 47% of the samples, followed by deletions at D8S504 (8p23.3), CTDP1-SHGC- 145820 (18qtel), KIT (4q11-q12), D1S427-FAF1 (1p32.3), D9S325 (9qtel), EIF4E (eukaryotic translation initiation factor 4E, 4q24), RB1 (13q14), and DXS7132 (Xq12) present in 5/17 (29.4%) of the samples. CONCLUSION: Our results confirm the presence of a specific pattern of chromosomal imbalances in cervical carcinoma and define specific targets that are suffering DNA copy number changes in this neoplasm

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Mapping and validation of a major QTL affecting resistance to pancreas disease (salmonid alphavirus) in Atlantic salmon (Salmo salar)

Pancreas disease (PD), caused by a salmonid alphavirus (SAV), has a large negative economic and animal welfare impact on Atlantic salmon aquaculture. Evidence for genetic variation in host resistance to this disease has been reported, suggesting that selective breeding may potentially form an important component of disease control. The aim of this study was to explore the genetic architecture of resistance to PD, using survival data collected from two unrelated populations of Atlantic salmon; one challenged with SAV as fry in freshwater (POP 1) and one challenged with SAV as post-smolts in sea water (POP 2). Analyses of the binary survival data revealed a moderate-to-high heritability for host resistance to PD in both populations (fry POP 1 h(2)~0.5; post-smolt POP 2 h(2)~0.4). Subsets of both populations were genotyped for single nucleotide polymorphism markers, and six putative resistance quantitative trait loci (QTL) were identified. One of these QTL was mapped to the same location on chromosome 3 in both populations, reaching chromosome-wide significance in both the sire- and dam-based analyses in POP 1, and genome-wide significance in a combined analysis in POP 2. This independently verified QTL explains a significant proportion of host genetic variation in resistance to PD in both populations, suggesting a common underlying mechanism for genetic resistance across lifecycle stages. Markers associated with this QTL are being incorporated into selective breeding programs to improve PD resistance