Stratigrafia ed assetto geometrico dell’Unità del Sannio nel settore settentrionale dei monti del Matese

New stratigraphic and biostratigraphic data arising from the realization of the Sheet No. 405 "Campobasso" of the new Geological map of Italy (1:50.000 scale - CARG Project) allowed, for the first time in this area, to stratigraphically and cartographically define all the ranges composing the basinal Sannio Unit Auct.. Structural analysis and the chronostratigraphic redefinition of siliciclastic deposits covering the Sannio Unit and the carbonate platform successions of the Matese- Frosolone Units, indicate two main evolutionary stages in the Miocene- Pliocene structuring of this portion of the Southern Apennines. In the first stage, starting before Serravallian times, E-verging contraction affected exclusively the basinal units together with their siliciclastic cover. During the second stage, beginning after early Messinian times, NE-verging compression involved both the basinal Sannio Unit and the Matese-Frosolone Units.UnpublishedISPRA - Roma, Italy2.2. Laboratorio di paleomagnetismorestricte

A tagging SNP in INSIG2 is associated with obesity-related phenotypes among Samoans

<p>Abstract</p> <p>Background</p> <p>A genome wide association study found significant association of a sequence variant, rs7566605, in the insulin-induced gene 2 (<it>INSIG2</it>) with obesity. However, the association remained inconclusive in follow-up studies. We tested for association of four tagging SNPs (tagSNPs) including this variant with body mass index (BMI) and abdominal circumference (ABDCIR) in the Samoans of the Western Pacific, a population with high levels of obesity.</p> <p>Methods</p> <p>We studied 907 adult Samoan participants from a longitudinal study of adiposity and cardiovascular disease risk in two polities, American Samoa and Samoa. Four tagSNPs were identified from the Chinese HapMap database based on pairwise <it>r</it>^{<it>2 </it>}of ≥0.8 and minor allele frequency of ≥0.05. Genotyping was performed using the TaqMan assay. Tests of association with BMI and ABDCIR were performed under the additive model.</p> <p>Results</p> <p>We did not find association of rs7566605 with either BMI or ABDCIR in any group of the Samoans. However, the most distally located tagSNPs in Intron 3 of the gene, rs9308762, showed significant association with both BMI (p-value 0.024) and ABDCIR (p-value 0.009) in the combined sample and with BMI (p-value 0.038) in the sample from Samoa.</p> <p>Conclusion</p> <p>Although rs7566605 was not significantly associated with obesity in our study population, we can not rule out the involvement of <it>INSIG2 </it>in obesity related traits as we found significant association of another tagSNP in <it>INSIG2 </it>with both BMI and ABDCIR. This study suggests the importance of comprehensive assessment of sequence variants within a gene in association studies.</p

INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men

Background A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G\u3eC, Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population. Methods We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18–40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test. Results Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 ± 5713 mm3 vs. GC/CC: n = 181; 268521 ± 5003 mm3; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% ± 1.74% vs. GC/CC: n = 93; 6.39% ± 1.82%; p = 0.035). Conclusion Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation

Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes

<p>Abstract</p> <p>Background</p> <p>A genome-wide scan in unrelated US Caucasians identified rs7001819 upstream of farnesyl-diphosphate farnesyltransferase 1 (<it>FDFT1</it>) and multiple variants within catenin (cadherin-associated protein), β-like 1 (<it>CTNNBL1</it>) to associate strongly with body mass index (BMI). The most significantly associating variants within <it>CTNNBL1 </it>including rs6013029 and rs6020846 were additionally confirmed to associate with morbid obesity in a French Caucasian case-control sample. The aim of this study was to investigate the impact of these three variants on obesity, through analyses of obesity-related quantitative traits, and case-control studies in large study samples of Danes.</p> <p>Methods</p> <p>The <it>FDFT1 </it>rs7001819, <it>CTNNBL1 </it>rs6013029 and rs6020846 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising 18,014 participants ascertained from; the population-based Inter99 cohort (<it>n </it>= 6,514), the ADDITION Denmark screening study cohort (<it>n </it>= 8,662), and a population-based sample (<it>n </it>= 680) and a type 2 diabetic patients group (<it>n </it>= 2,158) from Steno Diabetes Center.</p> <p>Results</p> <p>Both <it>CTNNBL1 </it>variants associated with body weight and height with per allele effect sizes of 1.0 [0.3–0.8] kg and 0.6 [0.2–0.9] cm, respectively, for the rs6020846 G-allele. No association was observed with BMI and waist circumference. In case-control studies neither of the <it>CTNNBL1 </it>variants showed association with overweight, obesity or morbid obesity (rs6013029: Odds Ratio (OR)_overweight= 1.02 [0.90–1.16], OR_obesity= 1.09 [0.95–1.25], OR_{morbidobesity}= 1.26 [0.91–1.74]; rs6020846: OR_overweight= 1.05 [0.93–1.18], OR_obesity= 1.13 [1.00–1.28], OR_{morbidobesity}= 1.17 [0.86–1.61]). However, in meta-analyses of the present and the previous study, both the rs6013029 T-allele and the rs6020846 G-allele increased the risk of developing morbid obesity (rs6013029: OR_combined= 1.36 [1.12–1.64], <it>p </it>= 0.002; rs6020846: OR_combined= 1.26 [1.06–1.51], <it>p </it>= 0.01), and obesity (rs6013029: OR_combined= 1.17 [1.04–1.31], <it>p </it>= 0.007; rs6020846: OR_combined= 1.17 [1.05–1.30], <it>p </it>= 0.004).</p> <p>The <it>FDFT1 </it>rs7001819 C-allele showed no association with obesity-related quantitative measures or dichotomous measures of overweight, obesity and morbid obesity.</p> <p>Conclusion</p> <p><it>CTNNBL1 </it>variants associated with body weight and height, and confer the risk of developing obesity in meta-analyses combining the present and a previous study. <it>FDFT1 </it>rs7001819 showed no association with obesity, neither when analysing quantitative traits nor when performing case-control studies of obesity.</p

Non-Replication of Genome-Wide Based Associations between Common Variants in INSIG2 and PFKP and Obesity in Studies of 18,014 Danes

(rs17782313) as genetic risk factors. = 2,158) from Steno Diabetes Center. rs17782313 were observed. rs7566605 may influence the level of BMI in combination with the level of physical activity

Association Analysis of the FTO Gene with Obesity in Children of Caucasian and African Ancestry Reveals a Common Tagging SNP

Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI≥95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r2 = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08–1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91–1.21; P = 0.49) and of 1.31 (95% CI 1.050–1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact

Gene expression profiling for molecular distinction and characterization of laser captured primary lung cancers

<p>Abstract</p> <p>Methods</p> <p>We examined gene expression profiles of tumor cells from 29 untreated patients with lung cancer (10 adenocarcinomas (AC), 10 squamous cell carcinomas (SCC), and 9 small cell lung cancer (SCLC)) in comparison to 5 samples of normal lung tissue (NT). The European and American methodological quality guidelines for microarray experiments were followed, including the stipulated use of laser capture microdissection for separation and purification of the lung cancer tumor cells from surrounding tissue.</p> <p>Results</p> <p>Based on differentially expressed genes, different lung cancer samples could be distinguished from each other and from normal lung tissue using hierarchical clustering. Comparing AC, SCC and SCLC with NT, we found 205, 335 and 404 genes, respectively, that were at least 2-fold differentially expressed (estimated false discovery rate: < 2.6%). Different lung cancer subtypes had distinct molecular phenotypes, which also reflected their biological characteristics. Differentially expressed genes in human lung tumors which may be of relevance in the respective lung cancer subtypes were corroborated by quantitative real-time PCR.</p> <p>Genetic programming (GP) was performed to construct a classifier for distinguishing between AC, SCC, SCLC, and NT. Forty genes, that could be used to correctly classify the tumor or NT samples, have been identified. In addition, all samples from an independent test set of 13 further tumors (AC or SCC) were also correctly classified.</p> <p>Conclusion</p> <p>The data from this research identified potential candidate genes which could be used as the basis for the development of diagnostic tools and lung tumor type-specific targeted therapies.</p

Replicating genotype-phenotype associations

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62757/1/447655a.pd