@article{nokey,

title = {Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.},

author = {Köttgen A and Albrecht E and Teumer A and et al and Tore Silvia and et al. },

doi = {10.1038/ng.2500},

year  = {2012},

date = {2012-12-23},

urldate = {2012-12-23},

journal = {Nature Genetics},

volume = {45},

number = {2},

pages = {145-154},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22962300,

title = {Chromosome-specific accumulation of aneuploidy in the aging mouse brain},

author = {F Faggioli and T Wang and J Vijg and C Montagna},

year  = {2012},

date = {2012-12-01},

journal = {Hum Mol Genet},

volume = {21},

number = {24},

pages = {5246--5253},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23106691,

title = {Proteomic profile identifies dysregulated pathways in Cornelia de Lange syndrome cells with distinct mutations in SMC1A and SMC3 genes},

author = {A Gimigliano and L Mannini and L Bianchi and M Puglia and M A Deardorff and S Menga and I D Krantz and A Musio and L Bini},

year  = {2012},

date = {2012-12-01},

journal = {J. Proteome Res.},

volume = {11},

number = {12},

pages = {6111--6123},

abstract = {Mutations in cohesin genes have been identified in Cornelia de Lange syndrome (CdLS), but its etiopathogenetic mechanisms are still poorly understood. To define biochemical pathways that are affected in CdLS, we analyzed the proteomic profile of CdLS cell lines carrying mutations in the core cohesin genes, SMC1A and SMC3. Dysregulated protein expression was found in CdLS probands compared to controls. The proteomics analysis was able to discriminate between probands harboring mutations in the different domains of the SMC proteins. In particular, proteins involved in the response to oxidative stress were specifically down-regulated in hinge mutated probands. In addition, the finding that CdLS cell lines show an increase in global oxidative stress argues that it could contribute to some CdLS phenotypic features such as premature physiological aging and genome instability. Finally, the c-MYC gene represents a convergent hub lying at the center of dysregulated pathways, and is down-regulated in CdLS. This study allowed us to highlight, for the first time, specific biochemical pathways that are affected in CdLS, providing plausible causal evidence for some of the phenotypic features seen in CdLS.},

note = {[PubMed Central:hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519430PMC3519430] [DOI:hrefhttps://dx.doi.org/10.1021/pr300760p10.1021/pr300760p] [PubMed:hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2310669123106691]},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{van_der_harst_seventy-five_2012,

title = {Seventy-five genetic loci influencing the human red blood cell},

author = {van der Harst, Pim and Zhang, Weihua and {Mateo Leach}, Irene and Rendon, Augusto and Verweij, Niek and Sehmi, Joban and Paul, Dirk S and Elling, Ulrich and Allayee, Hooman and Li, Xinzhong and Radhakrishnan, Aparna and Tan, Sian-Tsung and ... and Sanna, Serena and Uda, Manuela and Hicks, Andrew A and Penninger, Josef Martin and Gieger, Christian and Kooner, Jaspal S and Ouwehand, Willem H and Soranzo, Nicole and Chambers, John C},

doi = {10.1038/nature11677},

issn = {1476-4687},

year  = {2012},

date = {2012-12-01},

journal = {Nature},

volume = {492},

number = {7429},

pages = {369--375},

abstract = {Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sutin_impulsivity-related_2012,

title = {Impulsivity-related traits are associated with higher white blood cell counts},

author = {Angelina R Sutin and Yuri Milaneschi and Alessandra Cannas and Luigi Ferrucci and Manuela Uda and David Schlessinger and Alan B Zonderman and Antonio Terracciano},

doi = {10.1007/s10865-011-9390-0},

issn = {1573-3521},

year  = {2012},

date = {2012-12-01},

journal = {Journal of Behavioral Medicine},

volume = {35},

number = {6},

pages = {616--623},

abstract = {A chronically elevated white blood cell (WBC) count is a risk factor for morbidity and mortality. The present research tests whether facets of impulsivity-impulsiveness, excitement-seeking, self-discipline, and deliberation-are associated with chronically elevated WBC counts. Community-dwelling participants (N = 5,652) from Sardinia, Italy, completed a standard personality questionnaire and provided blood samples concurrently and again 3 years later. Higher scores on impulsivity, in particular impulsiveness and excitement-seeking, were related to higher total WBC counts and higher lymphocyte counts at both time points. Impulsiveness was a predictor of chronic inflammation: for every standard deviation difference in this trait, there was an almost 25% higher risk of elevated WBC counts at both time points (OR = 1.23, 95% CI = 1.10-1.38). These associations were mediated, in part, by smoking and body mass index. The findings demonstrate that links between psychological processes and immunity are not limited to acute stressors; stable personality dispositions are associated with a chronic inflammatory state.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rootsi_distinguishing_2012,

title = {Distinguishing the co-ancestries of haplogroup G Y-chromosomes in the populations of Europe and the Caucasus},

author = {Siiri Rootsi and Natalie M Myres and Alice A Lin and Mari J{ä}rve and Roy J King and Ildus Kutuev and Vicente M Cabrera and Elza K Khusnutdinova and K{ä}rt Varendi and Hovhannes Sahakyan and Doron M Behar and Rita Khusainova and Oleg Balanovsky and Elena Balanovska and Pavao Rudan and Levon Yepiskoposyan and Ardeshir Bahmanimehr and Shirin Farjadian and Alena Kushniarevich and Rene J Herrera and Viola Grugni and Vincenza Battaglia and Carmela Nici and Francesca Crobu and Sena Karachanak and Baharak {Hooshiar Kashani} and Massoud Houshmand and Mohammad H Sanati and Draga Toncheva and Antonella Lisa and Ornella Semino and Jacques Chiaroni and Julie {Di Cristofaro} and Richard Villems and Toomas Kivisild and Peter A Underhill},

doi = {10.1038/ejhg.2012.86},

issn = {1476-5438},

year  = {2012},

date = {2012-12-01},

journal = {European journal of human genetics: EJHG},

volume = {20},

number = {12},

pages = {1275--1282},

abstract = {Haplogroup G, together with J2 clades, has been associated with the spread of agriculture, especially in the European context. However, interpretations based on simple haplogroup frequency clines do not recognize underlying patterns of genetic diversification. Although progress has been recently made in resolving the haplogroup G phylogeny, a comprehensive survey of the geographic distribution patterns of the significant sub-clades of this haplogroup has not been conducted yet. Here we present the haplogroup frequency distribution and STR variation of 16 informative G sub-clades by evaluating 1472 haplogroup G chromosomes belonging to 98 populations ranging from Europe to Pakistan. Although no basal G-M201* chromosomes were detected in our data set, the homeland of this haplogroup has been estimated to be somewhere nearby eastern Anatolia, Armenia or western Iran, the only areas characterized by the co-presence of deep basal branches as well as the occurrence of high sub-haplogroup diversity. The P303 SNP defines the most frequent and widespread G sub-haplogroup. However, its sub-clades have more localized distribution with the U1-defined branch largely restricted to Near/Middle Eastern and the Caucasus, whereas L497 lineages essentially occur in Europe where they likely originated. In contrast, the only U1 representative in Europe is the G-M527 lineage whose distribution pattern is consistent with regions of Greek colonization. No clinal patterns were detected suggesting that the distributions are rather indicative of isolation by distance and demographic complexities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lo_iacono_osteopetrosis_2012,

title = {Osteopetrosis rescue upon RANKL administration to Rankl(-/-) mice: a new therapy for human RANKL-dependent ARO},

author = {Nadia {Lo Iacono} and Harry C Blair and Pietro L Poliani and Veronica Marrella and Francesca Ficara and Barbara Cassani and Fabio Facchetti and Elena Fontana and Matteo M Guerrini and Elisabetta Traggiai and Francesca Schena and Marianna Paulis and Stefano Mantero and Antonio Inforzato and Serenella Valaperta and Alessandra Pangrazio and Laura Crisafulli and Virginia Maina and Paul Kostenuik and Paolo Vezzoni and Anna Villa and Cristina Sobacchi},

doi = {10.1002/jbmr.1712},

issn = {1523-4681},

year  = {2012},

date = {2012-12-01},

journal = {Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research},

volume = {27},

number = {12},

pages = {2501--2510},

abstract = {In the last decades the molecular basis of monogenic diseases has been largely unraveled, although their treatment has often remained unsatisfactory. Autosomal recessive osteopetrosis (ARO) belongs to the small group of genetic diseases that are usually treated with hematopoietic stem cell transplantation (HSCT). However, this approach is not effective in the recently identified form carrying mutations in the receptor activator of NF-κB ligand (RANKL) gene. In this subset, therapy replacement approach based on RANKL delivery has a strong rationale. Here we demonstrate that the systematic administration of RANKL for 1 month to Rankl(-/-) mice, which closely resemble the human disease, significantly improves the bone phenotype and has beneficial effects on bone marrow, spleen and thymus; major adverse effects arise only when mice are clearly overtreated. Overall, we provide evidence that the pharmacological administration of RANKL represents the appropriate treatment option for RANKL-deficient ARO patients, to be validated in a pilot clinical trial.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23122588,

title = {Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease},

author = {A Indrieri and V A van Rahden and V Tiranti and M Morleo and D Iaconis and R Tammaro and I DÁmato and I Conte and I Maystadt and S Demuth and A Zvulunov and K Kutsche and M Zeviani and B Franco},

year  = {2012},

date = {2012-11-01},

volume = {91},

number = {5},

pages = {942--949},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23166348,

title = {Mutual antagonism between IP(3)RII and miRNA-133a regulates calcium signals and cardiac hypertrophy},

author = {F M Drawnel and D Wachten and J D Molkentin and M Maillet and J M Aronsen and F Swift and I Sjaastad and N Liu and D Catalucci and K Mikoshiba and C Hisatsune and H Okkenhaug and S R Andrews and M D Bootman and H L Roderick},

year  = {2012},

date = {2012-11-01},

journal = {J Cell Biol},

volume = {199},

number = {5},

pages = {783--798},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{1000_genomes_project_consortium_integrated_2012,

title = {An integrated map of genetic variation from 1,092 human genomes},

author = {1000 Genomes Project Consortium and Goncalo R Abecasis and Adam Auton and Lisa D Brooks and Mark A DePristo and Richard M Durbin and Robert E Handsaker and Hyun Min Kang and Gabor T Marth and Gil A McVean},

doi = {10.1038/nature11632},

issn = {1476-4687},

year  = {2012},

date = {2012-11-01},

journal = {Nature},

volume = {491},

number = {7422},

pages = {56--65},

abstract = {By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{fozza_t-cell_2012,

title = {T-cell receptor repertoire analysis in monozygotic twins concordant and discordant for type 1 diabetes.},

author = {Fozza, Claudio and Contini, Salvatore and Corda, Giovanna and Virdis, Patrizia and Galleu, Antonio and Bonfigli, Silvana and Pacifico, Adolfo and Maioli, Mario and Mastinu, Francesco and Pitzalis, Maristella and Cucca, Francesco and Longinotti, Maurizio},

doi = {10.1016/j.imbio.2012.01.002},

issn = {1878-3279 0171-2985},

year  = {2012},

date = {2012-09-01},

journal = {Immunobiology},

volume = {217},

number = {9},

pages = {920--925},

abstract = {Several data suggest that stochastic rearrangements of the TCR could play a pathogenic role in both disease predisposition and protection in type 1 diabetes (T1D). As twin sets offer an enormous potential in evaluating the role of genetic and environmental factors in susceptibility to disease, the main goal of this study was to assess whether the degree of sharing of the expressed TCR repertoire of twin pairs discordant for T1D differs from that of disease concordant pairs. We performed our analysis in 5 pairs of monozygotic twins, 3 of which were concordant and 2 discordant for T1D, by combining flow cytometry and CDR3 spectratyping on both CD4+ and CD8+ T-cells. Our data show that TCR repertoires show increased level of concordance within each twin pair, especially in CD8+ cells, in terms of mean BV expression levels on flow cytometry as well as of CDR3 patterns and frequencies of skewed or oligoclonal BV subfamilies on spectratyping. It is worth noting that the degree of similarity among twins seems to be independent of concordance or discordance for T1D. Our findings seem to suggest that in monozygotic twins with T1D the TCR repertoire is influenced by genetic factors more than by the presence of the autoimmune disorder itself.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cabras_ring_2012,

title = {Ring 20 syndrome mosaicism and epilepsy: a case with duplication of two BAC clones in 20q11.21-q11.22 defined by genome array-CGH},

author = {Valentina Cabras and Matteo Erriu and Mario Loi and Angela Milia and Caterina Montaldo and Anna Lisa Nucaro},

doi = {10.1136/jclinpath-2011-200573},

issn = {1472-4146},

year  = {2012},

date = {2012-09-01},

journal = {Journal of Clinical Pathology},

volume = {65},

number = {9},

pages = {851--853},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22484412,

title = {Mutation analysis of the ATP7B gene in a new group of Wilson's disease patients: contribution to diagnosis},

author = {M. B. Lepori and A. Zappu and S. Incollu and V. ì and E. Mameli and L. Demelia and A. M. Nurchi and L. Gheorghe and G. Maggiore and M. Sciveres and V. Leuzzi and G. Indolfi and L. é and C. Casali and P. Angeli and P. Barone and A. Cao and G. Loudianos},

year  = {2012},

date = {2012-08-26},

urldate = {2012-08-26},

journal = {Mol Cell Probes},

volume = {26},

number = {4},

pages = {147--150},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22614978,

title = {BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma},

author = {Colombino, M. and Capone, M. and Lissia, A. and Cossu, A. and Rubino, C. and De Giorgi, V. and Massi, D. and Fonsatti, E. and Staibano, S. and Nappi, O. and Pagani, E. and Casula, M. and Manca, A. and Sini, M. and Franco, R. and Botti, G. and Carac?, C. and Mozzillo, N. and Ascierto, P. A. and Palmieri, G.},

year  = {2012},

date = {2012-07-01},

journal = {J Clin Oncol},

volume = {30},

number = {20},

pages = {2522--2529},

abstract = {The prevalence of BRAF, NRAS, and p16CDKN2A mutations during melanoma progression remains inconclusive. We investigated the prevalence and distribution of mutations in these genes in different melanoma tissues. In all, 291 tumor tissues from 132 patients with melanoma were screened. Paired samples of primary melanomas (n = 102) and synchronous or asynchronous metastases from the same patients (n = 165) were included. Tissue samples underwent mutation analysis (automated DNA sequencing). Secondary lesions included lymph nodes (n = 84), and skin (n = 36), visceral (n = 25), and brain (n = 44) sites. BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15% NRAS); 62% in lymph nodes, 61% subcutaneous, 56% visceral, and 70% in brain sites. Mutations were observed in 63% of metastases (48% BRAF; 15% NRAS), a nonsignificant increase in mutation frequency after progression from primary melanoma. Of the paired samples, lymph nodes (93% consistency) and visceral metastases (96% consistency) presented a highly similar distribution of BRAF/NRAS mutations versus primary melanomas, with a significantly less consistent pattern in brain (80%) and skin metastases (75%). This suggests that independent subclones are generated in some patients. p16CDKN2A mutations were identified in 7% and 14% of primary melanomas and metastases, with a low consistency (31%) between secondary and primary tumor samples. In the era of targeted therapies, assessment of the spectrum and distribution of alterations in molecular targets among patients with melanoma is needed. Our findings about the prevalence of BRAF/NRAS/p16CDKN2A mutations in paired tumor lesions from patients with melanoma may be useful in the management of this disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rizzi_post-natal_2012,

title = {Post-natal cardiomyocytes can generate iPS cells with an enhanced capacity toward cardiomyogenic re-differentation},

author = {R Rizzi and E {Di Pasquale} and P Portararo and R Papait and P Cattaneo and M V G Latronico and C Altomare and L Sala and A Zaza and E Hirsch and L Naldini and G Condorelli and C Bearzi},

doi = {10.1038/cdd.2011.205},

issn = {1476-5403},

year  = {2012},

date = {2012-07-01},

journal = {Cell Death and Differentiation},

volume = {19},

number = {7},

pages = {1162--1174},

abstract = {Adult mammalian cells can be reprogrammed to a pluripotent state by forcing the expression of a few embryonic transcription factors. The resulting induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers. It is well known that post-natal cardiomyocytes (CMs) lack the capacity to proliferate. Here, we report that neonatal CMs can be reprogrammed to generate iPS cells that express embryonic-specific markers and feature gene-expression profiles similar to those of mouse embryonic stem (mES) cell and cardiac fibroblast (CF)-derived iPS cell populations. CM-derived iPS cells are able to generate chimeric mice and, moreover, re-differentiate toward CMs more efficiently then either CF-derived iPS cells or mES cells. The increased differentiation capacity is possibly related to CM-derived iPS cells retaining an epigenetic memory of the phenotype of their founder cell. CM-derived iPS cells may thus lead to new information on differentiation processes underlying cardiac differentiation and proliferation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{okada_meta-analysis_2012,

title = {Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations},

author = {Yukinori Okada and Xueling Sim and Min Jin Go and Jer-Yuarn Wu and Dongfeng Gu and Fumihiko Takeuchi and Atsushi Takahashi and Shiro Maeda and Tatsuhiko Tsunoda and Peng Chen and Su-Chi Lim and Tien-Yin Wong and Jianjun Liu and Terri L Young and Tin Aung and Mark Seielstad and Yik-Ying Teo and Young Jin Kim and Jong-Young Lee and Bok-Ghee Han and Daehee Kang and Chien-Hsiun Chen and Fuu-Jen Tsai and Li-Ching Chang and Cathy S -J Fann and Hao Mei and Dabeeru C Rao and James E Hixson and Shufeng Chen and Tomohiro Katsuya and Masato Isono and Toshio Ogihara and John C Chambers and Weihua Zhang and Jaspal S Kooner and KidneyGen Consortium and CKDGen Consortium and Eva Albrecht and GUGC consortium and Kazuhiko Yamamoto and Michiaki Kubo and Yusuke Nakamura and Naoyuki Kamatani and Norihiro Kato and Jiang He and Yuan-Tsong Chen and Yoon Shin Cho and E.-Shyong Tai and Toshihiro Tanaka},

doi = {10.1038/ng.2352},

issn = {1546-1718},

year  = {2012},

date = {2012-07-01},

journal = {Nature Genetics},

volume = {44},

number = {8},

pages = {904--909},

abstract = {Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{danjou_genetic_2012,

title = {Genetic modifiers of β-thalassemia and clinical severity as assessed by age at first transfusion},

author = {Fabrice Danjou and Franco Anni and Lucia Perseu and Stefania Satta and Carlo Dess{ì} and Maria Eliana Lai and Paolo Fortina and Marcella Devoto and Renzo Galanello},

doi = {10.3324/haematol.2011.053504},

issn = {1592-8721},

year  = {2012},

date = {2012-07-01},

journal = {Haematologica},

volume = {97},

number = {7},

pages = {989--993},

abstract = {BACKGROUND: The clinical and hematologic features of β-thalassemia are modulated by different factors, resulting in a wide range of clinical severity. The main factors are the type of disease-causing mutation and the ability to produce α-globin and γ-globin chains. In the present study we investigated the respective contributions of known modifiers to the prediction of the clinical severity of β-thalassemia as assessed by the patients' age at first transfusion. 

DESIGN AND METHODS: We studied the effect of seven loci in a cohort of 316 Sardinian patients with β(0)-thalassemia. In addition to characterizing the β-globin gene mutations, α-globin gene defects and HBG2:g.-158C>T polymorphism, we genotyped two different markers in the BCL11A gene and three in the HBS1L-MYB intergenic region using single nucleotide polymorphism microarrays, imputation and direct genotyping. We performed Cox proportional hazard analysis of the time to first transfusion. RESULTS: According to the resulting model, we were able to explain phenotypic severity to a large extent (Harrell's concordance index=0.72; Cox & Snell R(2)=0.394) and demonstrated that most of the model's discriminatory ability is attributable to the genetic variants affecting fetal hemoglobin production (HBG2:g.-158C>T, BCL11A and HBS1L-MYB loci: C-index=0.68, R(2)=0.272), while the remaining is due to α-globin gene defects and gender. Consequently, significantly distinct survival curves can be described in our population. 

CONCLUSIONS: This detailed analysis clarifies the impact of genetic modifiers on the clinical severity of the disease, measured by time to first transfusion, by determining their relative contributions in a homogeneous cohort of β(0)-thalassemia patients. It may also support clinical decisions regarding the beginning of transfusion therapy in patients with β-thalassemia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cagliani_trans-specific_2012,

title = {A trans-specific polymorphism in ZC3HAV1 is maintained by long-standing balancing selection and may confer susceptibility to multiple sclerosis.},

author = {Cagliani, R. and Guerini, F. R. and Fumagalli, M. and Riva, S. and Agliardi, C. and Galimberti, D. and Pozzoli, U. and Goris, A. and Dubois, B. and Fenoglio, C. and Forni, D. and Sanna, S. and Zara, I. and Pitzalis, M. and Zoledziewska, M. and Cucca, F. and Marini, F. and Comi, G. P. and Scarpini, E. and Bresolin, N. and Clerici, M. and Sironi, M.},

doi = {10.1093/molbev/mss002},

issn = {1537-1719 0737-4038},

year  = {2012},

date = {2012-06-01},

journal = {Mol Biol Evol},

volume = {29},

number = {6},

pages = {1599--1613},

abstract = {The human ZC3HAV1 gene encodes an antiviral protein. The longest splicing isoform of ZC3HAV1 contains a C-terminal PARP-like domain, which has evolved under positive selection in primates. We analyzed the evolutionary history of this same domain in humans and in Pan troglodytes. We identified two variants that segregate in both humans and chimpanzees; one of them (rs3735007) does not occur at a hypermutable site and accounts for a nonsynonymous substitution (Thr851Ile). The probability that the two trans-specific polymorphisms have occurred independently in the two lineages was estimated to be low (P = 0.0054), suggesting that at least one of them has arisen before speciation and has been maintained by selection. Population genetic analyses in humans indicated that the region surrounding the shared variants displays strong evidences of long-standing balancing selection. Selection signatures were also observed in a chimpanzee population sample. Inspection of 1000 Genomes data confirmed these findings but indicated that search for selection signatures using low-coverage whole-genome data may need masking of repetitive sequences. A case-control study of more than 1,000 individuals from mainland Italy indicated that the Thr851Ile SNP is significantly associated with susceptibility to multiple sclerosis (MS) (odds ratio [OR] = 1.47, 95% confidence intervals [CI]: 1.08-1.99},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{crobu_differentiation_2012,

title = {Differentiation of single cell derived human mesenchymal stem cells into cells with a neuronal phenotype: RNA and microRNA expression profile},

author = {Francesca Crobu and Veronica Latini and Maria Franca Marongiu and Valeria Sogos and Franca Scintu and Susanna Porcu and Carla Casu and Manuela Badiali and Adele Sanna and Maria Francesca Manchinu and Maria Serafina Ristaldi},

doi = {10.1007/s11033-011-1180-9},

issn = {1573-4978},

year  = {2012},

date = {2012-04-01},

journal = {Molecular Biology Reports},

volume = {39},

number = {4},

pages = {3995--4007},

abstract = {The adult bone marrow contains a subset of non-haematopoietic cells referred to as bone marrow mesenchymal stem cells (BMSCs). Mesenchymal stem cells (MSCs) have attracted immense research interest in the field of regenerative medicine due to their ability to be cultured for successive passages and multi-lineage differentiation. The molecular mechanisms governing the self-renewal and differentiation of MSCs remain largely unknown. In a previous paper we demonstrated the ability to induce human clonal MSCs to differentiate into cells with a neuronal phenotype (DMSCs). In the present study we evaluated gene expression profiles by Sequential Analysis of Gene Expression (SAGE) and microRNA expression profiles before and after the neuronal differentiation process. Various tissue-specific genes were weakly expressed in MSCs, including those of non-mesodermal origin, suggesting multiple potential tissue-specific differentiation, as well as stemness markers. Expression of OCT4, KLF4 and c-Myc cell reprogramming factors, which are modulated during the differentiation process, was also observed. Many peculiar nervous tissue genes were expressed at a high level in DMSCs, along with genes related to apoptosis. MicroRNA profiling and correlation with mRNA expression profiles allowed us to identify putative important genes and microRNAs involved in the differentiation of MSCs into neuronal-like cells. The profound difference in gene and microRNA expression patterns between MSCs and DMSCs indicates a real functional change during differentiation from MSCs to DMSCs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{camnasio_first_2012,

title = {The first reported generation of several induced pluripotent stem cell lines from homozygous and heterozygous Huntington's disease patients demonstrates mutation related enhanced lysosomal activity},

author = {Stefano Camnasio and Alessia {Delli Carri} and Angelo Lombardo and Iwona Grad and Caterina Mariotti and Alessia Castucci and Bj{ö}rn Rozell and Pietro {Lo Riso} and Valentina Castiglioni and Chiara Zuccato and Christelle Rochon and Yasuhiro Takashima and Giuseppe Diaferia and Ida Biunno and Cinzia Gellera and Marisa Jaconi and Austin Smith and Outi Hovatta and Luigi Naldini and Stefano {Di Donato} and Anis Feki and Elena Cattaneo},

doi = {10.1016/j.nbd.2011.12.042},

issn = {1095-953X},

year  = {2012},

date = {2012-04-01},

journal = {Neurobiology of Disease},

volume = {46},

number = {1},

pages = {41--51},

abstract = {Neuronal disorders, like Huntington's disease (HD), are difficult to study, due to limited cell accessibility, late onset manifestations, and low availability of material. The establishment of an in vitro model that recapitulates features of the disease may help understanding the cellular and molecular events that trigger disease manifestations. Here, we describe the generation and characterization of a series of induced pluripotent stem (iPS) cells derived from patients with HD, including two rare homozygous genotypes and one heterozygous genotype. We used lentiviral technology to transfer key genes for inducing reprogramming. To confirm pluripotency and differentiation of iPS cells, we used PCR amplification and immunocytochemistry to measure the expression of marker genes in embryoid bodies and neurons. We also analyzed teratomas that formed in iPS cell-injected mice. We found that the length of the pathological CAG repeat did not increase during reprogramming, after long term growth in vitro, and after differentiation into neurons. In addition, we observed no differences between normal and mutant genotypes in reprogramming, growth rate, caspase activation or neuronal differentiation. However, we observed a significant increase in lysosomal activity in HD-iPS cells compared to control iPS cells, both during self-renewal and in iPS-derived neurons. In conclusion, we have established stable HD-iPS cell lines that can be used for investigating disease mechanisms that underlie HD. The CAG stability and lysosomal activity represent novel observations in HD-iPS cells. In the future, these cells may provide the basis for a powerful platform for drug screening and target identification in HD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sarwar_interleukin-6_2012,

title = {Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies.},

author = {Sarwar, Nadeem and Butterworth, Adam S. and Freitag, Daniel F. and Gregson, John and Willeit, Peter and Gorman, Donal N. and Gao, Pei and Saleheen, Danish and Rendon, Augusto and Nelson, Christopher P. and Braund, Peter S. and Hall, Alistair S. and Chasman, Daniel I. and Tybjaerg-Hansen, Anne and Chambers, John C. and Benjamin, Emelia J. and Franks, Paul W. and Clarke, Robert and Wilde, Arthur A. M. and Trip, Mieke D. and Steri, Maristella and Witteman, Jacqueline C. M. and Qi, Lu and van der Schoot, C. Ellen and de Faire, Ulf and Erdmann, Jeanette and Stringham, Heather M. and Koenig, Wolfgang and Rader, Daniel J. and Melzer, David and Reich, David and Psaty, Bruce M. and Kleber, Marcus E. and Panagiotakos, Demosthenes B. and Willeit, Johann and Wennberg, Patrik and Woodward, Mark and Adamovic, Svetlana and Rimm, Eric B. and Meade, Tom W. and Gillum, Richard F. and Shaffer, Jonathan A. and Hofman, Albert and Onat, Altan and Sundstrom, Johan and Wassertheil-Smoller, Sylvia and Mellstrom, Dan and Gallacher, John and Cushman, Mary and Tracy, Russell P. and Kauhanen, Jussi and Karlsson, Magnus and Salonen, Jukka T. and Wilhelmsen, Lars and Amouyel, Philippe and Cantin, Bernard and Best, Lyle G. and Ben-Shlomo, Yoav and Manson, JoAnn E. and Davey-Smith, George and de Bakker, Paul I. W. and O'Donnell, Christopher J. and Wilson, James F. and Wilson, Anthony G. and Assimes, Themistocles L. and Jansson, John-Olov and Ohlsson, Claes and Tivesten, Asa and Ljunggren, Osten and Reilly, Muredach P. and Hamsten, Anders and Ingelsson, Erik and Cambien, Francois and Hung, Joseph and Thomas, G. Neil and Boehnke, Michael and Schunkert, Heribert and Asselbergs, Folkert W. and Kastelein, John J. P. and Gudnason, Vilmundur and Salomaa, Veikko and Harris, Tamara B. and Kooner, Jaspal S. and Allin, Kristine H. and Nordestgaard, Borge G. and Hopewell, Jemma C. and Goodall, Alison H. and Ridker, Paul M. and Holm, Hilma and Watkins, Hugh and Ouwehand, Willem H. and Samani, Nilesh J. and Kaptoge, Stephen and Di Angelantonio, Emanuele and Harari, Olivier and Danesh, John},

doi = {10.1016/S0140-6736(11)61931-4},

issn = {1474-547X 0140-6736},

year  = {2012},

date = {2012-03-01},

journal = {Lancet},

volume = {379},

number = {9822},

pages = {1205--1213},

abstract = {BACKGROUND: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. METHODS: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. FINDINGS: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele textgreater/=0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cattaneo_molecular_2012,

title = {Molecular chaperones as therapeutic targets to counteract proteostasis defects},

author = {Monica Cattaneo and Roberto Dominici and Marina Cardano and Giuseppe Diaferia and Ermanna Rovida and Ida Biunno},

doi = {10.1002/jcp.22856},

issn = {1097-4652},

year  = {2012},

date = {2012-03-01},

journal = {Journal of Cellular Physiology},

volume = {227},

number = {3},

pages = {1226--1234},

abstract = {The health of cells is preserved by the levels and correct folding states of the proteome, which is generated and maintained by the proteostasis network, an integrated biological system consisting of several cytoprotective and degradative pathways. Indeed, the health conditions of the proteostasis network is a fundamental prerequisite to life as the inability to cope with the mismanagement of protein folding arising from genetic, epigenetic, and micro-environment stress appears to trigger a whole spectrum of unrelated diseases. Here we describe the potential functional role of the proteostasis network in tumor biology and in conformational diseases debating on how the signaling branches of this biological system may be manipulated to develop more efficacious and selective therapeutic strategies. We discuss the dual strategy of these processes in modulating the folding activity of molecular chaperones in order to counteract the antithetic proteostasis deficiencies occurring in cancer and loss/gain of function diseases. Finally, we provide perspectives on how to improve the outcome of these disorders by taking advantage of proteostasis modeling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21769867,

title = {MiR-133a regulates collagen 1A1: potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension},

author = {G Castoldi and C R Di Gioia and C Bombardi and D Catalucci and B Corradi and M G Gualazzi and M Leopizzi and M Mancini and G Zerbini and G Condorelli and A Stella},

year  = {2012},

date = {2012-02-01},

journal = {J Cell Physiol},

volume = {227},

number = {2},

pages = {850--856},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{fozza_tcrbv20s1_2012,

title = {TCRBV20S1 polymorphism does not influence the susceptibility to type 1 diabetes and multiple sclerosis in the Sardinian population.},

author = {Fozza, Claudio and Zoledzieska, Magdalena and Pitzalis, Maristella and Simula, Maria Pina and Galleu, Antonio and Contini, Salvatore and Bonfigli, Silvana and Cucca, Francesco and Longinotti, Maurizio},

doi = {10.1007/s00251-011-0575-z},

issn = {1432-1211 0093-7711},

year  = {2012},

date = {2012-02-01},

journal = {Immunogenetics},

volume = {64},

number = {2},

pages = {153--154},

abstract = {Among the different T-cell receptor (TCR) BV20S1 polymorphisms, nucleotide substitution at position 524 results in the introduction of a stop codon, whose potential functional relevance is still unknown. We have recently showed in Sardinian subjects the most elevated allele frequency ever reported worldwide for this "null allele" (0.44). As this variant generates a gap in the TCR repertoire, this preliminary finding prompted us to further analyze the role of this polymorphism in the susceptibility to type 1 diabetes (T1D) and multiple sclerosis (MS), which are extremely common in this population. With this aim, we evaluated the influence of the TCRBV20S1 polymorphism by assessing it with the transmission disequilibirum test (TDT) in 652 T1D and 616 MS families, without detecting any significant difference. We conclude that the high frequency of this null allele in Sardinia is not directly related to the high incidence of these autoimmune diseases observed in this founder population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{gianfrancesco_nonsynonymous_2012,

title = {A nonsynonymous TNFRSF11A variation increases NFκB activity and the severity of Paget's disease},

author = {Fernando Gianfrancesco and Domenico Rendina and Marco {Di Stefano} and Alessandra Mingione and Teresa Esposito and Daniela Merlotti and Salvatore Gallone and Sara Magliocca and Alice Goode and Daniela Formicola and Giovanna Morello and Robert Layfield and Annalisa Frattini and Gianpaolo {De Filippo} and Ranuccio Nuti and Mark Searle and Pasquale Strazzullo and Giancarlo Isaia and Giuseppe Mossetti and Luigi Gennari},

doi = {10.1002/jbmr.542},

issn = {1523-4681},

year  = {2012},

date = {2012-02-01},

journal = {Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research},

volume = {27},

number = {2},

pages = {443--452},

abstract = {Mutations in the SQSTM1 gene were identified as a common cause of Paget's disease of bone (PDB) but experimental evidence demonstrated that SQSTM1 mutation is not sufficient to induce PDB in vivo. Here, we identified two nonsynonymous single nucleotide polymorphisms (SNPs) (C421T, H141Y and T575C, V192A) in the TNFRSF11A gene, associated with PDB and with the severity of phenotype in a large population of 654 unrelated patients that were previously screened for SQSTM1 gene mutations. The largest effect was found for the T575C variant, yielding an odds ratio of 1.29 (p = 0.003), with the C allele as the risk allele. Moreover, an even more significant p-value (p = 0.0002) was observed in the subgroup of patients with SQSTM1 mutation, with an odds ratio of 1.71. Interestingly, patients with the C allele also showed an increased prevalence of polyostotic disease (68%, 53%, and 51% in patients with CC, CT, and TT genotypes, respectively; p = 0.01), as well as an increased number of affected skeletal sites (2.9, 2.5, and 2.0 in patients with CC, CT, and TT genotypes, respectively},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22723555,

title = {Anti-CĐ3ε mAb improves thymic architecture and prevents autoimmune manifestations in a mouse model of Omenn syndrome: therapeutic implications},

author = {V Marrella and P L Poliani and E Fontana and A Casati and V Maina and B Cassani and F Ficara and M Cominelli and F Schena and M Paulis and E Traggiai and P Vezzoni and F Grassi and A Villa},

year  = {2012},

date = {2012-01-01},

journal = {Blood},

volume = {120},

number = {5},

pages = {1005--1014},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22810587,

title = {APJ acts as a dual receptor in cardiac hypertrophy},

author = {M C Scimia and C Hurtado and S Ray and S Metzler and K Wei and J Wang and C E Woods and N H Purcell and D Catalucci and T Akasaka and O F Bueno and G P Vlasuk and P Kaliman and R Bodmer and L H Smith and E Ashley and M Mercola and J H Brown and P Ruiz-Lozano},

year  = {2012},

date = {2012-01-01},

journal = {Nature},

volume = {488},

number = {7411},

pages = {394--398},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{matesanz_genome-wide_2012,

title = {Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1.},

author = {Matesanz, Fuencisla and Gonzalez-Perez, Antonio and Lucas, Miguel and Sanna, Serena and Gayan, Javier and Urcelay, Elena and Zara, Ilenia and Pitzalis, Maristella and Cavanillas, Maria L. and Arroyo, Rafael and Zoledziewska, Magdalena and Marrosu, Marisa and Fernandez, Oscar and Leyva, Laura and Alcina, Antonio and Fedetz, Maria and Moreno-Rey, Concha and Velasco, Juan and Real, Luis M. and Ruiz-Pena, Juan Luis and Cucca, Francesco and Ruiz, Agustin and Izquierdo, Guillermo},

doi = {10.1371/journal.pone.0036140},

issn = {1932-6203 1932-6203},

year  = {2012},

date = {2012-01-01},

journal = {PLoS One},

volume = {7},

number = {5},

pages = {e36140},

abstract = {Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 x 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{voight_metabochip_2012,

title = {The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits.},

author = {Voight, Benjamin F. and Kang, Hyun Min and Ding, Jun and Palmer, Cameron D. and Sidore, Carlo and Chines, Peter S. and Burtt, Noel P. and Fuchsberger, Christian and Li, Yanming and Erdmann, Jeanette and Frayling, Timothy M. and Heid, Iris M. and Jackson, Anne U. and Johnson, Toby and Kilpelainen, Tuomas O. and Lindgren, Cecilia M. and Morris, Andrew P. and Prokopenko, Inga and Randall, Joshua C. and Saxena, Richa and Soranzo, Nicole and Speliotes, Elizabeth K. and Teslovich, Tanya M. and Wheeler, Eleanor and Maguire, Jared and Parkin, Melissa and Potter, Simon and Rayner, N. William and Robertson, Neil and Stirrups, Kathleen and Winckler, Wendy and Sanna, Serena and Mulas, Antonella and Nagaraja, Ramaiah and Cucca, Francesco and Barroso, Ines and Deloukas, Panos and Loos, Ruth J. F. and Kathiresan, Sekar and Munroe, Patricia B. and Newton-Cheh, Christopher and Pfeufer, Arne and Samani, Nilesh J. and Schunkert, Heribert and Hirschhorn, Joel N. and Altshuler, David and McCarthy, Mark I. and Abecasis, Goncalo R. and Boehnke, Michael},

doi = {10.1371/journal.pgen.1002793},

issn = {1553-7404 1553-7390},

year  = {2012},

date = {2012-01-01},

journal = {PLoS Genet},

volume = {8},

number = {8},

pages = {e1002793},

abstract = {Genome-wide association studies have identified hundreds of loci for type 2 diabetes, coronary artery disease and myocardial infarction, as well as for related traits such as body mass index, glucose and insulin levels, lipid levels, and blood pressure. These studies also have pointed to thousands of loci with promising but not yet compelling association evidence. To establish association at additional loci and to characterize the genome-wide significant loci by fine-mapping, we designed the "Metabochip," a custom genotyping array that assays nearly 200,000 SNP markers. Here, we describe the Metabochip and its component SNP sets, evaluate its performance in capturing variation across the allele-frequency spectrum, describe solutions to methodological challenges commonly encountered in its analysis, and evaluate its performance as a platform for genotype imputation. The metabochip achieves dramatic cost efficiencies compared to designing single-trait follow-up reagents, and provides the opportunity to compare results across a range of related traits. The metabochip and similar custom genotyping arrays offer a powerful and cost-effective approach to follow-up large-scale genotyping and sequencing studies and advance our understanding of the genetic basis of complex human diseases and traits.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{li_likelihood-based_2012,

title = {A likelihood-based framework for variant calling and de novo mutation detection in families.},

author = {Li, Bingshan and Chen, Wei and Zhan, Xiaowei and Busonero, Fabio and Sanna, Serena and Sidore, Carlo and Cucca, Francesco and Kang, Hyun M. and Abecasis, Goncalo R.},

doi = {10.1371/journal.pgen.1002944},

issn = {1553-7404 1553-7390},

year  = {2012},

date = {2012-01-01},

journal = {PLoS Genet},

volume = {8},

number = {10},

pages = {e1002944},

abstract = {Family samples, which can be enriched for rare causal variants by focusing on families with multiple extreme individuals and which facilitate detection of de novo mutation events, provide an attractive resource for next-generation sequencing studies. Here, we describe, implement, and evaluate a likelihood-based framework for analysis of next generation sequence data in family samples. Our framework is able to identify variant sites accurately and to assign individual genotypes, and can handle de novo mutation events, increasing the sensitivity and specificity of variant calling and de novo mutation detection. Through simulations we show explicit modeling of family relationships is especially useful for analyses of low-frequency variants and that genotype accuracy increases with the number of individuals sequenced per family. Compared with the standard approach of ignoring relatedness, our methods identify and accurately genotype more variants, and have high specificity for detecting de novo mutation events. The improvement in accuracy using our methods over the standard approach is particularly pronounced for low-frequency variants. Furthermore the family-aware calling framework dramatically reduces Mendelian inconsistencies and is beneficial for family-based analysis. We hope our framework and software will facilitate continuing efforts to identify genetic factors underlying human diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nurnberg_gwas_2012,

title = {A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site.},

author = {Nurnberg, Sylvia T. and Rendon, Augusto and Smethurst, Peter A. and Paul, Dirk S. and Voss, Katrin and Thon, Jonathan N. and Lloyd-Jones, Heather and Sambrook, Jennifer G. and Tijssen, Marloes R. and Italiano, Joseph E. Jr and Deloukas, Panos and Gottgens, Berthold and Soranzo, Nicole and Ouwehand, Willem H.},

doi = {10.1182/blood-2012-01-401893},

issn = {1528-0020 0006-4971},

year  = {2012},

date = {2012-01-01},

journal = {Blood},

volume = {120},

number = {24},

pages = {4859--4868},

abstract = {We recently identified 68 genomic loci where common sequence variants are associated with platelet count and volume. Platelets are formed in the bone marrow by megakaryocytes, which are derived from hematopoietic stem cells by a process mainly controlled by transcription factors. The homeobox transcription factor MEIS1 is uniquely transcribed in megakaryocytes and not in the other lineage-committed blood cells. By ChIP-seq, we show that 5 of the 68 loci pinpoint a MEIS1 binding event within a group of 252 MK-overexpressed genes. In one such locus in DNM3, regulating platelet volume, the MEIS1 binding site falls within a region acting as an alternative promoter that is solely used in megakaryocytes, where allelic variation dictates different levels of a shorter transcript. The importance of dynamin activity to the latter stages of thrombopoiesis was confirmed by the observation that the inhibitor Dynasore reduced murine proplatelet for-mation in vitro.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Naitza2012,

title = {A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation.},

author = {Naitza, Silvia and Porcu, Eleonora and Steri, Maristella and Taub, Dennis D and Mulas, Antonella and Xiao, Xiang and Strait, James and Dei, Mariano and Lai, Sandra and Busonero, Fabio and Maschio, Andrea and Usala, Gianluca and Zoledziewska, Magdalena and Sidore, Carlo and Zara, Ilenia and Pitzalis, Maristella and Loi, Alessia and Virdis, Francesca and Piras, Roberta and Deidda, Francesca and Whalen, Michael B and Crisponi, Laura and Concas, Antonio and Podda, Carlo and Uzzau, Sergio and Scheet, Paul and Longo, Dan L and Lakatta, Edward and Abecasis, Gon{ç}alo R and Cao, Antonio and Schlessinger, David and Uda, Manuela and Sanna, Serena and Cucca, Francesco},

editor = {Sabeti, Pardis C.},

url = {http://dx.plos.org/10.1371/journal.pgen.1002480 http://www.ncbi.nlm.nih.gov/pubmed/22291609 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3266885},

doi = {10.1371/journal.pgen.1002480},

issn = {1553-7404},

year  = {2012},

date = {2012-01-01},

journal = {PLoS genetics},

volume = {8},

number = {1},

pages = {e1002480},

abstract = {Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL-6), the general measure of inflammation erythrocyte sedimentation rate (ESR), monocyte chemotactic protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs) and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals) for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals-5 of which were identified only with the custom arrays-and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10(-29)); for ESR, at the HBB (rs4910472, p = 2.31×10(-11)) and UCN119B/SPPL3 (rs11829037, p = 8.91×10(-10)) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10(-13)) and in CADM3 (rs3026968, p = 7.63×10(-13)); for hsCRP, within the CRP gene (rs3093077, p = 5.73×10(-21)), near DARC (rs3845624, p = 1.43×10(-10)), UNC119B/SPPL3 (rs11829037, p = 1.50×10(-14)), and ICOSLG/AIRE (rs113459440, p = 1.54×10(-08)) loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267); for ESR at CR1 (rs12567990) and TMEM57 (rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205), HNF1A (rs225918), and APOC-I (rs4420638). Our results improve the current knowledge of genetic variants underlying inflammation and provide novel clues for the understanding of the molecular mechanisms regulating this complex process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{stolk_meta-analyses_2012,

title = {Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways},

author = {Stolk, Lisette and Perry, John R B and Chasman, Daniel I and He, Chunyan and Mangino, Massimo and Sulem, Patrick and Barbalic, Maja and Broer, Linda and Byrne, Enda M and ... and Sanna, Serena and Schlessinger, David and Spector, Tim D and Stefansson, Kari and Streeten, Elizabeth A and Thorsteinsdottir, Unnur and Uda, Manuela and Uitterlinden, Andr{é} G and van Duijn, Cornelia M and V{ö}lzke, Henry and Murray, Anna and Murabito, Joanne M and Visser, Jenny A and Lunetta, Kathryn L},

doi = {10.1038/ng.1051},

issn = {1546-1718},

year  = {2012},

date = {2012-01-01},

journal = {Nature Genetics},

volume = {44},

number = {3},

pages = {260--268},

abstract = {To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-$kappa$B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{stenirri_study_2012,

title = {Study of FTMT and ABCA4 genes in a patient affected by age-related macular degeneration: identification and analysis of new mutations},

author = {Stefania Stenirri and Paolo Santambrogio and Marco Setaccioli and Benedetta Gaia Erba and Maria {Pia Manitto} and Ermanna Rovida and Maurizio Ferrari and Sonia Levi and Laura Cremonesi},

doi = {10.1515/cclm-2011-0854},

issn = {1437-4331},

year  = {2012},

date = {2012-01-01},

journal = {Clinical Chemistry and Laboratory Medicine},

volume = {50},

number = {6},

pages = {1021--1029},

abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a multifactorial disease for which an involvement of alterations in the retinal ABC transporter gene (ABCA4) is still debated. Oxidative stress in retinal pigment epithelial cells has been postulated to contribute to the pathogenesis of the disease. Mitochondrial ferritin (FtMt), an iron-sequestering protein, is expressed in cell types characterized by high metabolic activity and oxygen consumption, including human retina, suggesting a role in protecting mitochondria from iron-dependent oxidative damage. Based on these findings we wanted to investigate whether mutations in this gene could be found in AMD patients. 

METHODS: Mutational scanning of the FTMTgene was performed in a cohort of 50 patients affected by age-related macular degeneration. The ABCA4 gene was also scanned in one patient carrying an FtMt mutation. In silico analyses were carried out on the identified variants. The recombinant form of FtMt variant was expressed in Escherichia coli and biochemically characterized. 

RESULTS: One patient was found to be heterozygous for two previously unreported genetic changes: a complex FtMt mutation (c.437_450delinsCT: delAGGACATCAAGAAGinsCT) and a missense p.Leu973Phe (c.2919G>T) mutation in exon 20 of ABCA4. Computational analyses predicted a severe structural impairment for FtMt variant and a mild destabilizing effect for ABCA4. E. coli expression of recombinant FtMt variant yielded a highly insoluble protein that could not be renatured under in vitro conditions suitable for wild-type ferritins. 

CONCLUSIONS: Our findings suggest that the FtMt mutation may determine a condition similar to haploinsufficiency resulting in a reduced protection from iron-dependent oxidative stress in mitochondria.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{satta_delayed_2012,

title = {Delayed fetal hemoglobin switching in subjects with KLF1 gene mutation},

author = {Stefania Satta and Lucia Perseu and Liliana Maccioni and Nicolina Giagu and Renzo Galanello},

doi = {10.1016/j.bcmd.2011.10.003},

issn = {1096-0961},

year  = {2012},

date = {2012-01-01},

journal = {Blood Cells, Molecules & Diseases},

volume = {48},

number = {1},

pages = {22--24},

abstract = {Variations at the KLF1 gene have been associated with a series of human erythroid phenotypes including the In-(Lu) phenotype, hereditary persistence of fetal hemoglobin, congenital dyserythropoietic anemia, borderline HbA(2) and increased red blood cell protoporphyrin. Natural mutations have shown that KLF1 regulates gamma globin gene expression and its role in the switching from fetal to adult globin expression has been suggested by experimental studies. In this paper we report that subjects with S270X KLF1 mutations show a decrease of HbF levels with increasing age, supporting in vivo the role of KLF1 in hemoglobin switching in humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{piras_haplotype_2012,

title = {Haplotype affinities resolve a major component of goat (Capra hircus) MtDNA D-loop diversity and reveal specific features of the Sardinian stock},

author = {Daniela Piras and Maria Grazia Doro and Giuseppina Casu and Paola Maria Melis and Simona Vaccargiu and Ignazio Piras and Debora Parracciani and Roberta Stradoni and Bruno Frongia and Graziano Lai and Salvatore Sale and Walter Cattari and Roberto Piras and Ombretta Querci and Piergiorgio Demuro and Sandro Cui and Franco Atzori and Marco Mancosu and Francesca Marchiori and Rossana Cammelli and Alessandra Spiga and Pier Paolo Loddo and Gianfranco Pili and Roberto Boi and Giuseppe Argiolas and Paolo Mereu and Giovanni Giuseppe Leoni and Salvatore Naitana and Mario Pirastu and Andrea Novelletto},

doi = {10.1371/journal.pone.0030785},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

journal = {PloS One},

volume = {7},

number = {2},

pages = {e30785},

abstract = {Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity.We identified haplotype groups overrepresented in Sardinian goats as a result of founder effects. We found that breeders maintain diversity of matrilines most likely through equalization of the reproductive potential. Moreover, the relevant amount of inter-farm mtDNA diversity found does not increase proportionally with distance. Our results illustrate the effects of breeding practices on the composition of maternal gene pool and identify mtDNA types that may be considered in projects aimed at retrieving the maternal component of the oldest breeds of Sardinia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{marongiu_reversible_2012,

title = {Reversible disruption of pre-pulse inhibition in hypomorphic-inducible and reversible CB1-/- mice},

author = {Maria Franca Marongiu and Daniela Poddie and Susanna Porcu and Maria Francesca Manchinu and Maria Paola Castelli and Valeria Sogos and Valentina Bini and Roberto Frau and Elisabetta Caredda and Maria Collu and Maria Serafina Ristaldi},

doi = {10.1371/journal.pone.0035013},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

journal = {PloS One},

volume = {7},

number = {4},

pages = {e35013},

abstract = {Although several genes are implicated in the pathogenesis of schizophrenia, in animal models for such a severe mental illness only some aspects of the pathology can be represented (endophenotypes). Genetically modified mice are currently being used to obtain or characterize such endophenotypes. Since its cloning and characterization CB1 receptor has increasingly become of significant physiological, pharmacological and clinical interest. Recently, its involvement in schizophrenia has been reported. Among the different approaches employed, gene targeting permits to study the multiple roles of the endocannabinoid system using knockout ((-/-)) mice represent a powerful model but with some limitations due to compensation. To overcome such a limitation, we have generated an inducible and reversible tet-off dependent tissue-specific CB1(-/-) mice where the CB1R is re-expressed exclusively in the forebrain at a hypomorphic level due to a mutation (IRh-CB1(-/-)) only in absence of doxycycline (Dox). In such mice, under Dox(+) or vehicle, as well as in wild-type (WT) and CB1(-/-), two endophenotypes motor activity (increased in animal models of schizophrenia) and pre-pulse inhibition (PPI) of startle reflex (disrupted in schizophrenia) were analyzed. Both CB1(-/-) and IRh-CB1(-/-) showed increased motor activity when compared to WT animals. The PPI response, unaltered in WT and CB1(-/-) animals, was on the contrary highly and significantly disrupted only in Dox(+) IRh-CB1(-/-) mice. Such a response was easily reverted after either withdrawal from Dox or haloperidol treatment. This is the first Inducible and Reversible CB1(-/-) mice model to be described in the literature. It is noteworthy that the PPI disruption is not present either in classical full CB1(-/-) mice or following acute administration of rimonabant. Such a hypomorphic model may provide a new tool for additional in vivo and in vitro studies of the physiological and pathological roles of cannabinoid system in schizophrenia and in other psychiatric disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cocco_vitamin_2012,

title = {Vitamin Đ responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis associated alleles},

author = {Eleonora Cocco and Alessandra Meloni and Maria Rita Murru and Daniela Corongiu and Stefania Tranquilli and Elisabetta Fadda and Raffaele Murru and Lucia Schirru and Maria Antonietta Secci and Gianna Costa and Isadora Asunis and Stefania Cuccu and Giuseppe Fenu and Lorena Lorefice and Nicola Carboni and Gioia Mura and Maria Cristina Rosatelli and Maria Giovanna Marrosu},

doi = {10.1371/journal.pone.0041678},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

journal = {PloS One},

volume = {7},

number = {7},

pages = {e41678},

abstract = {Vitamin D response elements (VDREs) have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and 112 healthy subjects). Sequencing of the DRB1 promoter region revealed a homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cabras_cryptic_2012,

title = {Cryptic chromosome rearrangements in five patients, with normal and/or abnormal karyotypes, associated with mental retardation, autism and/or epilepsy, detected by BAC genome array-CGH},

author = {V Cabras and A Milia and C Montaldo and A Nucaro},

doi = {10.14712/23362936.2015.11},

issn = {1214-6994},

year  = {2012},

date = {2012-01-01},

journal = {Prague Medical Report},

volume = {113},

number = {4},

pages = {279--288},

abstract = {This report describes the usefulness of the BAC genome array-CGH platform in the detection of cryptic rearrangements. We examined ten patients with normal and/or abnormal karyotypes and dysmorphic features, associated with mental retardation, autism and/or epilepsy. This approach led us to discover further cryptic chromosomal rearrangements, not previously detected by conventional cytogenetic procedures, and allowed us to better delineate genotype/phenotype correlation. Our experience shows the validity of the BAC platform as a reliable method for genome-wide screening of chromosomal aberrations in patient with idiopathic mental retardation and/or in association with autism and epilepsy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21925467,

title = {Gut-tropic Ŧ cells that express integrin α4β7 and CCR9 are required for induction of oral immune tolerance in mice},

author = {B Cassani and E J Villablanca and F J Quintana and P E Love and A Lacy-Hulbert and W S Blaner and T Sparwasser and S B Snapper and H L Weiner and J R Mora},

year  = {2011},

date = {2011-12-01},

journal = {Gastroenterology},

volume = {141},

number = {6},

pages = {2109--2118},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22040217,

title = {Novel and recurrent JAG1 mutations in patients with tetralogy of Fallot},

author = {Guida, V. and Chiappe, F. and Ferese, R. and Usala, G. and Maestrale, G. and Iannascoli, C. and Bellacchio, E. and Mingarelli, R. and Digilio, M. C. and Marino, B. and Uda, M. and De Luca, A. and Dallapiccola, B.},

year  = {2011},

date = {2011-12-01},

journal = {Clin Genet},

volume = {80},

number = {6},

pages = {591--594},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hunt_rare_2011,

title = {Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry.},

author = {Hunt, Karen A. and Smyth, Deborah J. and Balschun, Tobias and Ban, Maria and Mistry, Vanisha and Ahmad, Tariq and Anand, Vidya and Barrett, Jeffrey C. and Bhaw-Rosun, Leena and Bockett, Nicholas A. and Brand, Oliver J. and Brouwer, Elisabeth and Concannon, Patrick and Cooper, Jason D. and Dias, Kerith-Rae M. and van Diemen, Cleo C. and Dubois, Patrick C. and Edkins, Sarah and Folster-Holst, Regina and Fransen, Karin and Glass, David N. and Heap, Graham A. R. and Hofmann, Sylvia and Huizinga, Tom W. J. and Hunt, Sarah and Langford, Cordelia and Lee, James and Mansfield, John and Marrosu, Maria Giovanna and Mathew, Christopher G. and Mein, Charles A. and Muller-Quernheim, Joachim and Nutland, Sarah and Onengut-Gumuscu, Suna and Ouwehand, Willem and Pearce, Kerra and Prescott, Natalie J. and Posthumus, Marcel D. and Potter, Simon and Rosati, Giulio and Sambrook, Jennifer and Satsangi, Jack and Schreiber, Stefan and Shtir, Corina and Simmonds, Matthew J. and Sudman, Marc and Thompson, Susan D. and Toes, Rene and Trynka, Gosia and Vyse, Timothy J. and Walker, Neil M. and Weidinger, Stephan and Zhernakova, Alexandra and Zoledziewska, Magdalena and Weersma, Rinse K. and Gough, Stephen C. L. and Sawcer, Stephen and Wijmenga, Cisca and Parkes, Miles and Cucca, Francesco and Franke, Andre and Deloukas, Panos and Rich, Stephen S. and Todd, John A. and van Heel, David A.},

doi = {10.1038/ng.1037},

issn = {1546-1718 1061-4036},

year  = {2011},

date = {2011-12-01},

journal = {Nat Genet},

volume = {44},

number = {1},

pages = {3--5},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21302287,

title = {Unexpectedly low mutation rates in beta-myosin heavy chain and cardiac myosin binding protein genes in Italian patients with hypertrophic cardiomyopathy},

author = {R Roncarati and M V Latronico and B Musumeci and S Aurino and A Torella and M L Bang and G S Jotti and A A Puca and M Volpe and V Nigro and C Autore and G Condorelli},

year  = {2011},

date = {2011-11-01},

journal = {J Cell Physiol},

volume = {226},

number = {11},

pages = {2894--2900},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{terracciano_meta-analysis_2011,

title = {Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking.},

author = {Terracciano, A. and Esko, T. and Sutin, A. R. and de Moor, M. H. M. and Meirelles, O. and Zhu, G. and Tanaka, T. and Giegling, I. and Nutile, T. and Realo, A. and Allik, J. and Hansell, N. K. and Wright, M. J. and Montgomery, G. W. and Willemsen, G. and Hottenga, J.-J. and Friedl, M. and Ruggiero, D. and Sorice, R. and Sanna, S. and Cannas, A. and Raikkonen, K. and Widen, E. and Palotie, A. and Eriksson, J. G. and Cucca, F. and Krueger, R. F. and Lahti, J. and Luciano, M. and Smoller, J. W. and van Duijn, C. M. and Abecasis, G. R. and Boomsma, D. I. and Ciullo, M. and Costa, P. T. Jr and Ferrucci, L. and Martin, N. G. and Metspalu, A. and Rujescu, D. and Schlessinger, D. and Uda, M.},

doi = {10.1038/tp.2011.42},

issn = {2158-3188 2158-3188},

year  = {2011},

date = {2011-10-01},

journal = {Transl Psychiatry},

volume = {1},

pages = {e49},

abstract = {The tendency to seek stimulating activities and intense sensations define excitement-seeking, a personality trait akin to some aspects of sensation-seeking. This trait is a central feature of extraversion and is a component of the multifaceted impulsivity construct. Those who score high on measures of excitement-seeking are more likely to smoke, use other drugs, gamble, drive recklessly, have unsafe/unprotected sex and engage in other risky behaviors of clinical and social relevance. To identify common genetic variants associated with the Excitement-Seeking scale of the Revised NEO Personality Inventory, we performed genome-wide association studies in six samples of European ancestry (N=7860), and combined the results in a meta-analysis. We identified a genome-wide significant association between the Excitement-Seeking scale and rs7600563 (P=2 x 10(-8)). This single-nucleotide polymorphism maps within the catenin cadherin-associated protein, alpha 2 (CTNNA2) gene, which encodes for a brain-expressed alpha-catenin critical for synaptic contact. The effect of rs7600563 was in the same direction in all six samples, but did not replicate in additional samples (N=5105). The results provide insight into the genetics of excitement-seeking and risk-taking, and are relevant to hyperactivity, substance use, antisocial and bipolar disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{chambers_genome-wide_2011,

title = {Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.},

author = {Chambers, John C. and Zhang, Weihua and Sehmi, Joban and Li, Xinzhong and Wass, Mark N. and Van der Harst, Pim and Holm, Hilma and Sanna, Serena and Kavousi, Maryam and Baumeister, Sebastian E. and Coin, Lachlan J. and Deng, Guohong and Gieger, Christian and Heard-Costa, Nancy L. and Hottenga, Jouke-Jan and Kuhnel, Brigitte and Kumar, Vinod and Lagou, Vasiliki and Liang, Liming and Luan, Jian'an and Vidal, Pedro Marques and Mateo Leach, Irene and O'Reilly, Paul F. and Peden, John F. and Rahmioglu, Nilufer and Soininen, Pasi and Speliotes, Elizabeth K. and Yuan, Xin and Thorleifsson, Gudmar and Alizadeh, Behrooz Z. and Atwood, Larry D. and Borecki, Ingrid B. and Brown, Morris J. and Charoen, Pimphen and Cucca, Francesco and Das, Debashish and de Geus, Eco J. C. and Dixon, Anna L. and Doring, Angela and Ehret, Georg and Eyjolfsson, Gudmundur I. and Farrall, Martin and Forouhi, Nita G. and Friedrich, Nele and Goessling, Wolfram and Gudbjartsson, Daniel F. and Harris, Tamara B. and Hartikainen, Anna-Liisa and Heath, Simon and Hirschfield, Gideon M. and Hofman, Albert and Homuth, Georg and Hypponen, Elina and Janssen, Harry L. A. and Johnson, Toby and Kangas, Antti J. and Kema, Ido P. and Kuhn, Jens P. and Lai, Sandra and Lathrop, Mark and Lerch, Markus M. and Li, Yun and Liang, T. Jake and Lin, Jing-Ping and Loos, Ruth J. F. and Martin, Nicholas G. and Moffatt, Miriam F. and Montgomery, Grant W. and Munroe, Patricia B. and Musunuru, Kiran and Nakamura, Yusuke and O'Donnell, Christopher J. and Olafsson, Isleifur and Penninx, Brenda W. and Pouta, Anneli and Prins, Bram P. and Prokopenko, Inga and Puls, Ralf and Ruokonen, Aimo and Savolainen, Markku J. and Schlessinger, David and Schouten, Jeoffrey N. L. and Seedorf, Udo and Sen-Chowdhry, Srijita and Siminovitch, Katherine A. and Smit, Johannes H. and Spector, Timothy D. and Tan, Wenting and Teslovich, Tanya M. and Tukiainen, Taru and Uitterlinden, Andre G. and Van der Klauw, Melanie M. and Vasan, Ramachandran S. and Wallace, Chris and Wallaschofski, Henri and Wichmann, H.-Erich and Willemsen, Gonneke and Wurtz, Peter and Xu, Chun and Yerges-Armstrong, Laura M. and Abecasis, Goncalo R. and Ahmadi, Kourosh R. and Boomsma, Dorret I. and Caulfield, Mark and Cookson, William O. and van Duijn, Cornelia M. and Froguel, Philippe and Matsuda, Koichi and McCarthy, Mark I. and Meisinger, Christa and Mooser, Vincent and Pietilainen, Kirsi H. and Schumann, Gunter and Snieder, Harold and Sternberg, Michael J. E. and Stolk, Ronald P. and Thomas, Howard C. and Thorsteinsdottir, Unnur and Uda, Manuela and Waeber, Gerard and Wareham, Nicholas J. and Waterworth, Dawn M. and Watkins, Hugh and Whitfield, John B. and Witteman, Jacqueline C. M. and Wolffenbuttel, Bruce H. R. and Fox, Caroline S. and Ala-Korpela, Mika and Stefansson, Kari and Vollenweider, Peter and Volzke, Henry and Schadt, Eric E. and Scott, James and Jarvelin, Marjo-Riitta and Elliott, Paul and Kooner, Jaspal S.},

doi = {10.1038/ng.970},

issn = {1546-1718 1061-4036},

year  = {2011},

date = {2011-10-01},

journal = {Nat Genet},

volume = {43},

number = {11},

pages = {1131--1138},

abstract = {Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21852550,

title = {MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo},

author = {D Torella and C Iaconetti and D Catalucci and G M Ellison and A Leone and C D Waring and A Bochicchio and C Vicinanza and I Aquila and A Curcio and G Condorelli and C Indolfi},

year  = {2011},

date = {2011-09-01},

journal = {Circ Res},

volume = {109},

number = {8},

pages = {880--893},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sanna_fine_2011,

title = {Fine mapping of five loci associated with low-density lipoprotein cholesterol detects variants that double the explained heritability.},

author = {Sanna, Serena and Li, Bingshan and Mulas, Antonella and Sidore, Carlo and Kang, Hyun M. and Jackson, Anne U. and Piras, Maria Grazia and Usala, Gianluca and Maninchedda, Giuseppe and Sassu, Alessandro and Serra, Fabrizio and Palmas, Maria Antonietta and Wood, William H. 3rd and Njolstad, Inger and Laakso, Markku and Hveem, Kristian and Tuomilehto, Jaakko and Lakka, Timo A. and Rauramaa, Rainer and Boehnke, Michael and Cucca, Francesco and Uda, Manuela and Schlessinger, David and Nagaraja, Ramaiah and Abecasis, Goncalo R.},

doi = {10.1371/journal.pgen.1002198},

issn = {1553-7404 1553-7390},

year  = {2011},

date = {2011-07-01},

journal = {PLoS Genet},

volume = {7},

number = {7},

pages = {e1002198},

abstract = {Complex trait genome-wide association studies (GWAS) provide an efficient strategy for evaluating large numbers of common variants in large numbers of individuals and for identifying trait-associated variants. Nevertheless, GWAS often leave much of the trait heritability unexplained. We hypothesized that some of this unexplained heritability might be due to common and rare variants that reside in GWAS identified loci but lack appropriate proxies in modern genotyping arrays. To assess this hypothesis, we re-examined 7 genes (APOE, APOC1, APOC2, SORT1, LDLR, APOB, and PCSK9) in 5 loci associated with low-density lipoprotein cholesterol (LDL-C) in multiple GWAS. For each gene, we first catalogued genetic variation by re-sequencing 256 Sardinian individuals with extreme LDL-C values. Next, we genotyped variants identified by us and by the 1000 Genomes Project (totaling 3,277 SNPs) in 5,524 volunteers. We found that in one locus (PCSK9) the GWAS signal could be explained by a previously described low-frequency variant and that in three loci (PCSK9, APOE, and LDLR) there were additional variants independently associated with LDL-C, including a novel and rare LDLR variant that seems specific to Sardinians. Overall, this more detailed assessment of SNP variation in these loci increased estimates of the heritability of LDL-C accounted for by these genes from 3.1% to 6.5%. All association signals and the heritability estimates were successfully confirmed in a sample of approximately 10,000 Finnish and Norwegian individuals. Our results thus suggest that focusing on variants accessible via GWAS can lead to clear underestimates of the trait heritability explained by a set of loci. Further, our results suggest that, as prelude to large-scale sequencing efforts, targeted re-sequencing efforts paired with large-scale genotyping will increase estimates of complex trait heritability explained by known loci.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21598388,

title = {A comparative MudPIŦ analysis identifies different expression profiles in heart compartments},

author = {C Comunian and F Rusconi and A De Palma and P Brunetti and D Catalucci and P L Mauri},

year  = {2011},

date = {2011-06-01},

journal = {Proteomics},

volume = {11},

number = {11},

pages = {2320--2328},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21424129,

title = {Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (AĐI) in melanoma cells},

author = {Manca, A. and Sini, M. C. and Izzo, F. and Ascierto, P. A. and Tatangelo, F. and Botti, G. and Gentilcore, G. and Capone, M. and Mozzillo, N. and Rozzo, C. and Cossu, A. and Tanda, F. and Palmieri, G.},

year  = {2011},

date = {2011-06-01},

volume = {25},

number = {6},

pages = {1495--1502},

abstract = {Arginine deiminase (ADI), an arginine-degrading enzyme, has been used in the treatment of tumours sensitive to arginine deprivation, such as malignant melanoma (MM) and hepatocellular carcinoma (HCC). Endogenous production of arginine is mainly dependent on activity of ornithine transcarbamylase (OTC) and argininosuccinate synthetase (ASS) enzymes. We evaluated the effect of ADI treatment on OTC and ASS expression in a series of melanoma cell lines. Twenty-five primary melanoma cell lines and normal fibroblasts as controls underwent cell proliferation assays and Western blot analyses in the presence or absence of ADI. Tissue sections from primary MMs (N = 20) and HCCs (N = 20) were investigated by immunohistochemistry for ASS expression. Overall, 21/25 (84%) MM cell lines presented a cell growth inhibition by ADI treatment; none of them presented constitutive detectable levels of the ASS protein. However, 7/21 (33%) ADI-sensitive melanoma cell lines presented markedly increased expression levels of the ASS protein following ADI treatment, with a significantly higher IC50 median value. Growth was not inhibited and the IC50 was not reached among the remaining 4/25 (16%) MM cell lines; all of them showed constitutive ASS expression. The OTC protein was found expressed in all melanoma cell lines before and after the ADI treatment. Lack of ASS immunostaining was observed in all analyzed in vivo specimens. Our findings suggest that response to ADI treatment in melanoma is significantly correlated with the ability of cells to express ASS either constitutively at basal level (inducing drug resistance) or after the treatment (reducing sensitivity to ADI).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{herholz_differential_2011,

title = {Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders},

author = {Jana Herholz and Alessandra Meloni and Mara Marongiu and Francesca Chiappe and Manila Deiana and Carmen Roche Herrero and Giuseppe Zampino and Hanan Hamamy and Yusra Zalloum and Per Erik Waaler and Giangiorgio Crisponi and Laura Crisponi and Frank Rutsch},

doi = {10.1038/ejhg.2010.253},

issn = {1476-5438},

year  = {2011},

date = {2011-05-01},

journal = {European journal of human genetics: EJHG},

volume = {19},

number = {5},

pages = {525--533},

abstract = {Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) are disorders caused by mutations in CRLF1. The two syndromes share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia, associated with death in most cases in the first years of life. To evaluate a potential genotype/phenotype correlation and whether CS and CISS1 represent two allelic diseases or manifestations at different ages of the same disorder, we carried out a detailed clinical analysis of 19 patients carrying mutations in CRLF1. We studied the functional significance of the mutations found in CRLF1, providing evidence that phenotypic severity of the two disorders mainly depends on altered kinetics of secretion of the mutated CRLF1 protein. On the basis of these findings, we believe that the two syndromes, CS and CISS1, represent manifestations of the same disorder, with different degrees of severity. We suggest renaming the two genetic entities CS and CISS1 with the broader term of Sohar-Crisponi syndrome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}