@article{pmid22022514,

title = {Single-cell analysis of ploidy and centrosomes underscores the peculiarity of normal hepatocytes},

author = {F Faggioli and P Vezzoni and C Montagna},

year  = {2011},

date = {2011-01-01},

journal = {PLoS One},

volume = {6},

number = {10},

pages = {e26080},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21283782,

title = {Application of a new method for GWAS in a related case/control sample with known pedigree structure: identification of new loci for nephrolithiasis},

author = {Tore, S. and Casula, S. and Casu, G. and Concas, M. P. and Pistidda, P. and Persico, I. and Sassu, A. and Maestrale, G. B. and Mele, C. and Caruso, M. R. and Bonerba, B. and Usai, P. and Deiana, I. and Thornton, T. and Pirastu, M. and Forabosco, P.},

year  = {2011},

date = {2011-01-01},

journal = {PLoS Genet},

volume = {7},

number = {1},

pages = {e1001281},

abstract = {In contrast to large GWA studies based on thousands of individuals and large meta-analyses combining GWAS results, we analyzed a small case/control sample for uric acid nephrolithiasis. Our cohort of closely related individuals is derived from a small, genetically isolated village in Sardinia, with well-characterized genealogical data linking the extant population up to the 16(th) century. It is expected that the number of risk alleles involved in complex disorders is smaller in isolated founder populations than in more diverse populations, and the power to detect association with complex traits may be increased when related, homogeneous affected individuals are selected, as they are more likely to be enriched with and share specific risk variants than are unrelated, affected individuals from the general population. When related individuals are included in an association study, correlations among relatives must be accurately taken into account to ensure validity of the results. A recently proposed association method uses an empirical genotypic covariance matrix estimated from genome-screen data to allow for additional population structure and cryptic relatedness that may not be captured by the genealogical data. We apply the method to our data, and we also investigate the properties of the method, as well as other association methods, in our highly inbred population, as previous applications were to outbred samples. The more promising regions identified in our initial study in the genetic isolate were then further investigated in an independent sample collected from the Italian population. Among the loci that showed association in this study, we observed evidence of a possible involvement of the region encompassing the gene LRRC16A, already associated to serum uric acid levels in a large meta-analysis of 14 GWAS, suggesting that this locus might lead a pathway for uric acid metabolism that may be involved in gout as well as in nephrolithiasis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21807894,

title = {Klf1 affects DNase II-alpha expression in the central macrophage of a fetal liver erythroblastic island: a non-cell-autonomous role in definitive erythropoiesis},

author = {Porcu, S. and Manchinu, M. F. and Marongiu, M. F. and Sogos, V. and Poddie, D. and Asunis, I. and Porcu, L. and Marini, M. G. and Moi, P. and Cao, A. and Grosveld, F. and Ristaldi, M. S.},

year  = {2011},

date = {2011-01-01},

journal = {Mol Cell Biol},

volume = {31},

number = {19},

pages = {4144--4154},

abstract = {A key regulatory gene in definitive erythropoiesis is the erythroid Kruppel-like factor (Eklf or Klf1). Klf1 knockout (KO) mice die in utero due to severe anemia, while residual circulating red blood cells retain their nuclei. Dnase2a is another critical gene in definitive erythropoiesis. Dnase2a KO mice are also affected by severe anemia and die in utero. DNase II-alpha is expressed in the central macrophage of erythroblastic islands (CMEIs) of murine fetal liver. Its main role is to digest the DNA of the extruded nuclei of red blood cells during maturation. Circulating erythrocytes retain their nuclei in Dnase2a KO mice. Here, we show that Klf1 is expressed in CMEIs and that it binds and activates the promoter of Dnase2a. We further show that Dnase2a is severely downregulated in the Klf1 KO fetal liver. We propose that this downregulation of Dnase2a in the CMEI contributes to the Klf1 KO phenotype by a non-cell-autonomous mechanism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sanna2011,

title = {Fine Mapping of Five Loci Associated with Low-Density Lipoprotein Cholesterol Detects Variants That Double the Explained Heritability},

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

editor = {Greg Gibson},

url = {https://doi.org/10.1371/journal.pgen.1002198},

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

year  = {2011},

date = {2011-01-01},

journal = {PLoS Genetics},

volume = {7},

number = {7},

pages = {e1002198},

publisher = {Public Library of Science (PLoS)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{fozza_keratitis-ichthyosis-deafness_2011,

title = {Keratitis-Ichthyosis-Deafness Syndrome, Atypical Connexin GJB2 Gene Mutation, and Peripheral Ŧ-Cell Lymphoma: More Than a Random Association?},

author = {Fozza, Claudio and Poddie, Fausto and Contini, Salvatore and Galleu, Antonio and Cottoni, Francesca and Longinotti, Maurizio and Cucca, Francesco},

doi = {10.1155/2011/848461},

issn = {2090-6579 2090-6579},

year  = {2011},

date = {2011-01-01},

journal = {Case Rep Hematol},

volume = {2011},

pages = {848461},

abstract = {Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder characterized by skin lesions, neurosensorial hypoacusia, and keratitis, usually due to the c.148G --textgreater A mutation involving the connexin 26 gene. We report on a KID patient who showed the atypical c.101T --textgreater C mutation and developed a T-cell lymphoma so far never described in this group of patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{dottorini_serum_2011,

title = {Serum IgE reactivity profiling in an asthma affected cohort},

author = {Tania Dottorini and Gabriella Sole and Luisa Nunziangeli and Francesca Baldracchini and Nicola Senin and Giorgio Mazzoleni and Carla Proietti and Lenuta Balaci and Andrea Crisanti},

doi = {10.1371/journal.pone.0022319},

issn = {1932-6203},

year  = {2011},

date = {2011-01-01},

journal = {PloS One},

volume = {6},

number = {8},

pages = {e22319},

abstract = {BACKGROUND: Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear. 

METHODS: We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema. 

RESULTS: Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09). An artificial neural network (ANN)-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations. 

CONCLUSIONS: These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20557886,

title = {Ŧhe androgen derivative 5alpha-androstane-3beta,17beta-diol inhibits tumor necrosis factor alpha and lipopolysaccharide induced inflammatory response in human endothelial cells and in mice aorta},

author = {G D Norata and P Cattaneo and A Poletti and A L Catapano},

year  = {2010},

date = {2010-09-01},

volume = {212},

number = {1},

pages = {100--106},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20547828,

title = {Ħomeostatic expansion of autoreactive immunoglobulin-secreting cells in the Rag2 mouse model of Omenn syndrome},

author = {B Cassani and P L Poliani and V Marrella and F Schena and A V Sauer and M Ravanini and D Strina and C E Busse and S Regenass and H Wardemann and A Martini and F Facchetti and M van der Burg and A G Rolink and P Vezzoni and F Grassi and E Traggiai and A Villa},

year  = {2010},

date = {2010-07-01},

journal = {J Exp Med},

volume = {207},

number = {7},

pages = {1525--1540},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20331458b,

title = {Regulation of the human HBA genes by KLF4 in erythroid cell lines},

author = { M. G. Marini and L. Porcu and I. Asunis and M. G. Loi and M. S. Ristaldi and S. Porcu and T. Ikuta and A. Cao and P. Moi},

year  = {2010},

date = {2010-06-01},

journal = {Br J Haematol},

volume = {149},

number = {5},

pages = {748--758},

abstract = {KLF1/EKLF and related Krueppel-like factors (KLFs) are variably implicated in the regulation of the HBB-like globin genes. Prompted by the observation that four KLF sites are distributed in the human alpha-globin gene (HBA) promoter, we investigated if KLFs could also act to modulate the expression of the HBA genes. Among the KLFs tested, only KLF4/GKLF bound specifically to three out of four alpha-globin KLF sites. The occupancy of the same sites by KLF4 in vivo was confirmed by chromatin immunoprecipitation assays with KLF4-specific antibodies. In luciferase reporter assays in MEL cells, high levels of the wild type HBA promoter, but not mutated promoters bearing point mutations that disrupted KLF4-DNA binding, were transactivated by over-expression of KLF4. In K562 cells, induced KLF4 expression with a Tet-off regulated cassette stimulated the expression of the endogenous HBA genes. In a complementary assay in the same cell line, knocking down KLF4 with lentiviral delivered sh-RNAs caused a parallel decrease in the transcription of the HBA genes. All experiments combined support a regulatory role of KLF4 in the control of HBA gene expression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20331458,

title = {Regulation of the human ĦBA genes by KLF4 in erythroid cell lines},

author = { M. G. Marini and L. Porcu and I. Asunis and M. G. Loi and M. S. Ristaldi and S. Porcu and T. Ikuta and A. Cao and P. Moi},

year  = {2010},

date = {2010-06-01},

journal = {Br J Haematol},

volume = {149},

number = {5},

pages = {748--758},

abstract = {KLF1/EKLF and related Krueppel-like factors (KLFs) are variably implicated in the regulation of the HBB-like globin genes. Prompted by the observation that four KLF sites are distributed in the human alpha-globin gene (HBA) promoter, we investigated if KLFs could also act to modulate the expression of the HBA genes. Among the KLFs tested, only KLF4/GKLF bound specifically to three out of four alpha-globin KLF sites. The occupancy of the same sites by KLF4 in vivo was confirmed by chromatin immunoprecipitation assays with KLF4-specific antibodies. In luciferase reporter assays in MEL cells, high levels of the wild type HBA promoter, but not mutated promoters bearing point mutations that disrupted KLF4-DNA binding, were transactivated by over-expression of KLF4. In K562 cells, induced KLF4 expression with a Tet-off regulated cassette stimulated the expression of the endogenous HBA genes. In a complementary assay in the same cell line, knocking down KLF4 with lentiviral delivered sh-RNAs caused a parallel decrease in the transcription of the HBA genes. All experiments combined support a regulatory role of KLF4 in the control of HBA gene expression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sanna2010,

title = {Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis.},

author = {Sanna, Serena and Pitzalis, Maristella and Zoledziewska, Magdalena and Zara, Ilenia and Sidore, Carlo and Murru, Raffaele and Whalen, Michael B and Busonero, Fabio and Maschio, Andrea and Costa, Gianna and Melis, Maria Cristina and Deidda, Francesca and Poddie, Fausto and Morelli, Laura and Farina, Gabriele and Li, Yun and Dei, Mariano and Lai, Sandra and Mulas, Antonella and Cuccuru, Gianmauro and Porcu, Eleonora and Liang, Liming and Zavattari, Patrizia and Moi, Loredana and Deriu, Elisa and Urru, M Francesca and Bajorek, Michele and Satta, Maria Anna and Cocco, Eleonora and Ferrigno, Paola and Sotgiu, Stefano and Pugliatti, Maura and Traccis, Sebastiano and Angius, Andrea and Melis, Maurizio and Rosati, Giulio and Abecasis, Gon{ç}alo R and Uda, Manuela and Marrosu, Maria Giovanna and Schlessinger, David and Cucca, Francesco},

url = {http://www.nature.com/doifinder/10.1038/ng.584 http://www.ncbi.nlm.nih.gov/pubmed/20453840 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3786343},

doi = {10.1038/ng.584},

issn = {1546-1718},

year  = {2010},

date = {2010-06-01},

journal = {Nature genetics},

volume = {42},

number = {6},

pages = {495--7},

abstract = {A genome-wide association scan of approximately 6.6 million genotyped or imputed variants in 882 Sardinian individuals with multiple sclerosis (cases) and 872 controls suggested association of CBLB gene variants with disease, which was confirmed in 1,775 cases and 2,005 controls (rs9657904, overall P = 1.60 x 10(-10)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20190016,

title = {A synonymous mutation in the CFTR gene causes aberrant splicing in an italian patient affected by a mild form of cystic fibrosis},

author = { V. Faa' and A. Coiana and F. Incani and L. Costantino and A. Cao and M. C. Rosatelli},

year  = {2010},

date = {2010-05-01},

journal = {J Mol Diagn},

volume = {12},

number = {3},

pages = {380--383},

abstract = {Mutations within exons are responsible for aberrant splicing of pre-mRNA in several human disease genes and in some viral systems. Nonsense, missense, and even synonymous mutations can induce aberrant skipping of the mutant exon, producing nonfunctional proteins. In this paper, we describe the effect on the splicing efficiency of the synonymous variant 2811 G>T [Gly893Gly] detected in a patient of Italian descent affected by a mild form of cystic fibrosis, until now mentioned as sequence variation with unknown functional consequences. The study, performed through DNA as well as RNA analyses, shows that this mutation creates a new 5' splice site within exon 15, resulting in a transcript lacking 76 amino acid residues. Although this aberrant splicing causes a shorter exon 15, the downstream exonic sequence from exon 16 to the end of the open reading frame is in frame. This study indicates that apparently neutral polymorphism, which may be erroneously classified as nonpathogenic, may indeed led to aberrant splicing thereby resulting in defective protein.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{morelli_comparison_2010,

title = {A comparison of Y-chromosome variation in Sardinia and Anatolia is more consistent with cultural rather than demic diffusion of agriculture.},

author = {Morelli, Laura and Contu, Daniela and Santoni, Federico and Whalen, Michael B. and Francalacci, Paolo and Cucca, Francesco},

doi = {10.1371/journal.pone.0010419},

issn = {1932-6203 1932-6203},

year  = {2010},

date = {2010-04-01},

journal = {PLoS One},

volume = {5},

number = {4},

pages = {e10419},

abstract = {Two alternative models have been proposed to explain the spread of agriculture in Europe during the Neolithic period. The demic diffusion model postulates the spreading of farmers from the Middle East along a Southeast to Northeast axis. Conversely, the cultural diffusion model assumes transmission of agricultural techniques without substantial movements of people. Support for the demic model derives largely from the observation of frequency gradients among some genetic variants, in particular haplogroups defined by single nucleotide polymorphisms (SNPs) in the Y-chromosome. A recent network analysis of the R-M269 Y chromosome lineage has purportedly corroborated Neolithic expansion from Anatolia, the site of diffusion of agriculture. However, the data are still controversial and the analyses so far performed are prone to a number of biases. In the present study we show that the addition of a single marker, DYSA7.2, dramatically changes the shape of the R-M269 network into a topology showing a clear Western-Eastern dichotomy not consistent with a radial diffusion of people from the Middle East. We have also assessed other Y-chromosome haplogroups proposed to be markers of the Neolithic diffusion of farmers and compared their intra-lineage variation--defined by short tandem repeats (STRs)--in Anatolia and in Sardinia, the only Western population where these lineages are present at appreciable frequencies and where there is substantial archaeological and genetic evidence of pre-Neolithic human occupation. The data indicate that Sardinia does not contain a subset of the variability present in Anatolia and that the shared variability between these populations is best explained by an earlier, pre-Neolithic dispersal of haplogroups from a common ancestral gene pool. Overall, these results are consistent with the cultural diffusion and do not support the demic model of agriculture diffusion.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{meloni_daxx_2010,

title = {DAXX is a new AIRE-interacting protein},

author = {Alessandra Meloni and Edoardo Fiorillo and Denise Corda and Federica Incani and Maria Luisa Serra and Antonella Contini and Antonio Cao and Maria Cristina Rosatelli},

doi = {10.1074/jbc.M109.037747},

issn = {1083-351X},

year  = {2010},

date = {2010-04-01},

journal = {The Journal of Biological Chemistry},

volume = {285},

number = {17},

pages = {13012--13021},

abstract = {The AIRE protein plays a remarkable role as a regulator of central tolerance by controlling the promiscuous expression of tissue-specific antigens in thymic medullary epithelial cells. Defects in the AIRE gene cause the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, a rare disease frequent in Iranian Jews, Finns, and Sardinian population. To this day, the precise function of the AIRE protein in regulating transcription and its interacting proteins has yet to be entirely clarified. The knowledge of novel AIRE interactors and their precise role will improve our knowledge of its biological activity and address some of the foremost autoimmunity-related questions. In this study, we have used a yeast two-hybrid system to identify AIRE-interacting proteins. This approach led us to the discovery of a new AIRE-interacting protein called DAXX. The protein is known to be a multifunctional adaptor with functions both in apoptosis and in transcription regulation pathways. The interaction between AIRE and DAXX has been validated by in vivo coimmunoprecipitation analysis and colocalization study in mammalian cells. The interaction has been further confirmed by showing in transactivation assays that DAXX exerts a strong repressive role on the transcriptional activity of AIRE.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20209145,

title = {The forkhead transcription factor Foxl2 is sumoylated in both human and mouse: sumoylation affects its stability, localization, and activity},

author = {Marongiu, M. and Deiana, M. and Meloni, A. and Marcia, L. and Puddu, A. and Cao, A. and Schlessinger, D. and Crisponi, L.},

year  = {2010},

date = {2010-03-01},

journal = {PLoS One},

volume = {5},

number = {3},

pages = {e9477},

abstract = {The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES) and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gonadal sex determination and ovary development and revealed its antagonism of Sox9, the effector of male testis development. To help to define the regulatory activities of FOXL2, we looked for interacting proteins. Based on yeast two-hybrid screening, we found that FOXL2 interacts with PIAS1 and UBC9, both parts of the sumoylation machinery. We showed that human FOXL2 is sumoylated in transfected cell lines, and that endogenous mouse Foxl2 is comparably sumoylated. This modification changes its cellular localization, stability and transcriptional activity. It is intriguing that similar sumoylation and regulatory consequences have also been reported for SOX9, the male counterpart of FOXL2 in somatic gonadal tissues.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{faa_alpha_2010,

title = {Alpha globin gene duplications in beta thalassemia patients with intact beta globin gene},

author = {Valeria Fa{à} and Maddalena Masala and Antonio Cao and Maria Cristina Rosatelli},

doi = {10.1016/j.bcmd.2009.12.009},

issn = {1096-0961},

year  = {2010},

date = {2010-03-01},

journal = {Blood Cells, Molecules & Diseases},

volume = {44},

number = {3},

pages = {156--158},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20109747,

title = {Đefect of regulatory Ŧ cells in patients with Omenn syndrome},

author = {B Cassani and P L Poliani and D Moratto and C Sobacchi and V Marrella and L Imperatori and D Vairo and A Plebani and S Giliani and P Vezzoni and F Facchetti and F Porta and L D Notarangelo and A Villa and R Badolato},

year  = {2010},

date = {2010-01-01},

journal = {J Allergy Clin Immunol},

volume = {125},

number = {1},

pages = {209--216},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19953639,

title = {Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations},

author = {A Pangrazio and M Pusch and E Caldana and A Frattini and E Lanino and P M Tamhankar and S Phadke and A G Lopez and P Orchard and E Mihci and M Abinun and M Wright and K Vettenranta and I Bariae and D Melis and I Tezcan and C Baumann and F Locatelli and M Zecca and E Horwitz and L S Mansour and M Van Roij and P Vezzoni and A Villa and C Sobacchi},

year  = {2010},

date = {2010-01-01},

journal = {Hum Mutat},

volume = {31},

number = {1},

pages = {E1071--1080},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20644257,

title = {MŦORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice},

author = {D Zhang and R Contu and M V Latronico and J Zhang and J L Zhang and R Rizzi and D Catalucci and S Miyamoto and K Huang and M Ceci and Y Gu and N D Dalton and K L Peterson and K L Guan and J H Brown and J Chen and N Sonenberg and G Condorelli},

year  = {2010},

date = {2010-01-01},

journal = {J Clin Invest},

volume = {120},

number = {8},

pages = {2805--2816},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{tolea_sex-specific_2010,

title = {Sex-specific correlates of walking speed in a wide age-ranged population.},

author = {Tolea, Magdalena I. and Costa, Paul T. and Terracciano, Antonio and Griswold, Michael and Simonsick, Eleanor M. and Najjar, Samer S. and Scuteri, Angelo and Deiana, Barbara and Orru, Marco and Masala, Marco and Uda, Manuela and Schlessinger, David and Ferrucci, Luigi},

doi = {10.1093/geronb/gbp130},

issn = {1758-5368 1079-5014},

year  = {2010},

date = {2010-01-01},

journal = {J Gerontol B Psychol Sci Soc Sci},

volume = {65B},

number = {2},

pages = {174--184},

abstract = {The goals of this cross-sectional study were to explore correlates of walking speed in a large wide age-ranged population and to identify factors affecting lower walking speed at older ages. Participants were 3,872 community-dwelling adults in the first follow-up of the SardiNIA study who completed a 4-m walking test. Sex-specific correlates of walking speed included marital status, height, waist circumference, pulse wave velocity, comorbidity, subjective health, strength, and personality. Effect modifiers of the age-walking speed association included extraversion (textless55 years},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hilner_designing_2010,

title = {Designing and implementing sample and data collection for an international genetics study: the Type 1 Diabetes Genetics Consortium (Ŧ1DGC).},

author = {Hilner, Joan E. and Perdue, Letitia H. and Sides, Elizabeth G. and Pierce, June J. and Wagner, Ana M. and Aldrich, Alan and Loth, Amanda and Albret, Lotte and Wagenknecht, Lynne E. and Nierras, Concepcion and Akolkar, Beena},

doi = {10.1177/1740774510373497},

issn = {1740-7753 1740-7745},

year  = {2010},

date = {2010-01-01},

journal = {Clin Trials},

volume = {7},

number = {1 Suppl},

pages = {S5--S32},

abstract = {BACKGROUND AND PURPOSE: The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide. METHODS: T1DGC was organized into four regional networks (Asia-Pacific, Europe, North America, and the United Kingdom) and a Coordinating Center. A Steering Committee, with representatives from each network, the Coordinating Center, and the funding organizations, was responsible for T1DGC operations. The Coordinating Center, with regional network representatives, developed study documents and data systems. Each network established laboratories for: DNA extraction and cell line production; human leukocyte antigen genotyping; and autoantibody measurement. Samples were tracked from the point of collection, processed at network laboratories and stored for deposit at National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories. Phenotypic data were collected and entered into the study database maintained by the Coordinating Center. RESULTS: T1DGC achieved its original ASP recruitment goal. In response to research design changes, the T1DGC infrastructure also recruited trios, cases, and controls. Results of genetic analyses have identified many novel regions that affect susceptibility to type 1 diabetes. T1DGC created a resource of data and samples that is accessible to the research community. LIMITATIONS: Participation in T1DGC was declined by some countries due to study requirements for the processing of samples at network laboratories and/or final deposition of samples in NIDDK Central Repositories. Re-contact of participants was not included in informed consent templates, preventing collection of additional samples for functional studies. CONCLUSIONS: T1DGC implemented a distributed, regional network structure to reach ASP recruitment targets. The infrastructure proved robust and flexible enough to accommodate additional recruitment. T1DGC has established significant resources that provide a basis for future discovery in the study of type 1 diabetes genetics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{maioli_number_2010,

title = {Number of autoantibodies and HLA genotype, more than high titers of glutamic acid decarboxylase autoantibodies, predict insulin dependence in latent autoimmune diabetes of adults.},

author = {Maioli, M. and Pes, G. M. and Delitala, G. and Puddu, L. and Falorni, A. and Tolu, F. and Lampis, R. and Orru, V. and Secchi, G. and Cicalo, A. M. and Floris, R. and Madau, G. F. and Pilosu, R. M. and Whalen, M. and Cucca, F.},

doi = {10.1530/EJE-10-0427},

issn = {1479-683X 0804-4643},

year  = {2010},

date = {2010-01-01},

journal = {Eur J Endocrinol},

volume = {163},

number = {4},

pages = {541--549},

abstract = {OBJECTIVE: In latent autoimmune diabetes of adults (LADA), the progression into insulin-dependent diabetes is usually faster than in type 2 diabetes (T2D) but the factors influencing this progression are not completely known. In this study, we searched for sensitive markers associated with early development of insulin dependence. DESIGN: The screening of 5568 T2D patients for glutamic acid decarboxylase autoantibodies (GAD65Ab) identified 276 LADA patients (M=131; F=145) and in 251 of them, tyrosine phosphatase-2 (IA-2Ab) and thyroperoxidase autoantibodies (TPOAbs), some clinical features and genotype variation of the main type 1 diabetes (T1D) disease susceptibility loci (HLA-DRB1 and HLA-DQB1) were analyzed. RESULTS: Four years after the diagnosis of diabetes, high GAD65Ab titer was not significantly associated with faster progression toward insulin deficiency (P=0.104). Patients with GAD65Ab and TPOAb or IA-2Ab or triple positivity for both islet and TPOAbs (GAD65Ab/IA-2Ab/TPOAb) showed a significantly faster disease progression (P=0.002). Among 104 TPOAb-positive LADA patients, 10 received replacement therapy (l-thyroxine), 43 showed high TSH levels (62.7% developed insulin dependence), and 3 had hyperthyroidism treated with methimazole. Multivariate analysis revealed a significant effect on disease progression only for TPOAb (P=0.022), female gender (P=0.036), low body mass index (BMI; P=0.001), and T1D high/intermediate risk HLA-DRB1/DQB1 genotypes grouped (P=0.020). CONCLUSIONS: High GAD65Ab titers per se are not a major risk factor for disease progression in LADA, while the number of positive autoantibodies and HLA DRB1-DQB1 genotypes at high risk for T1D are significant predictors. Moreover, clinical characteristics such as low BMI and female gender are more likely to identify patients who will require insulin therapy within 4 years of diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19679637,

title = {Nebulin plays a direct role in promoting strong actin-myosin interactions},

author = {M L Bang and M Caremani and E Brunello and R Littlefield and R L Lieber and J Chen and V Lombardi and M Linari},

year  = {2009},

date = {2009-12-01},

journal = {FASEB J},

volume = {23},

number = {12},

pages = {4117--4125},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{faa_characterization_2009,

title = {Characterization of a disease-associated mutation affecting a putative splicing regulatory element in intron 6b of the cystic fibrosis transmembrane conductance regulator (CFTR) gene},

author = {Valeria Faà and Federica Incani and Alessandra Meloni and Denise Corda and Maddalena Masala and Maria A Baffico and Manuela Seia and Antonio Cao and Cristina M Rosatelli},

doi = {10.1074/jbc.M109.032623},

issn = {1083-351X},

year  = {2009},

date = {2009-10-01},

journal = {The Journal of Biological Chemistry},

volume = {284},

number = {44},

pages = {30024--30031},

abstract = {Cystic fibrosis (CF) is a common recessive disorder caused by >1600 mutations in the CF transmembrane conductance regulator (CFTR) gene. About 13% of CFTR mutations are classified as "splicing mutations," but for almost 40% of these, their role in affecting the pre-mRNA splicing of the gene is not yet defined. In this work, we describe a new splicing mutation detected in three unrelated Italian CF patients. By DNA analyses and mRNA studies, we identified the c.1002-1110_1113delTAAG mutation localized in intron 6b of the CFTR gene. At the mRNA level, this mutation creates an aberrant inclusion of a sequence of 101 nucleotides between exons 6b and 7. This sequence corresponds to a portion of intron 6b and resembles a cryptic exon because it is characterized by an upstream ag and a downstream gt sequence, which are most probably recognized as 5'- and 3'-splice sites by the spliceosome. Through functional analysis of this splicing defect, we show that this mutation abolishes the interaction of the splicing regulatory protein heterogeneous nuclear ribonucleoprotein A2/B1 with an intronic splicing regulatory element and creates a new recognition motif for the SRp75 splicing factor, causing activation of the cryptic exon. Our results show that the c.1002-1110_1113delTAAG mutation creates a new intronic splicing regulatory element in intron 6b of the CFTR gene exclusively recognized by SRp75.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19553676,

title = {Bone morphogenetic protein 15 (BMP15) acts as a BMP and Wnt inhibitor during early embryogenesis},

author = {E Di Pasquale and A H Brivanlou},

year  = {2009},

date = {2009-09-01},

journal = {J Biol Chem},

volume = {284},

number = {38},

pages = {26127--26136},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{sanna_common_2009,

title = {Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia},

author = {Serena Sanna and Fabio Busonero and Andrea Maschio and Patrick F McArdle and Gianluca Usala and Mariano Dei and Sandra Lai and Antonella Mulas and Maria Grazia Piras and Lucia Perseu and Marco Masala and Mara Marongiu and Laura Crisponi and Silvia Naitza and Renzo Galanello and Gon{ç}alo R Abecasis and Alan R Shuldiner and David Schlessinger and Antonio Cao and Manuela Uda},

doi = {10.1093/hmg/ddp203},

issn = {1460-2083},

year  = {2009},

date = {2009-07-01},

journal = {Human Molecular Genetics},

volume = {18},

number = {14},

pages = {2711--2718},

abstract = {Bilirubin, resulting largely from the turnover of hemoglobin, is found in the plasma in two main forms: unconjugated or conjugated with glucuronic acid. Unconjugated bilirubin is transported into hepatocytes. There, it is glucuronidated by UGT1A1 and secreted into the bile canaliculi. We report a genome wide association scan in 4300 Sardinian individuals for total serum bilirubin levels. In addition to the two known loci previously involved in the regulation of bilirubin levels, UGT1A1 (P = 6.2 x 10(-62)) and G6PD (P = 2.5 x 10(-8)), we observed a strong association on chromosome 12 within the SLCO1B3 gene (P = 3.9 x 10(-9)). Our findings were replicated in an independent sample of 1860 Sardinians and in 832 subjects from the Old Order Amish (combined P textless 5 x 10(-14)). We also show that SLC01B3 variants contribute to idiopathic mild unconjugated hyperbilirubinemia. Thus, SLC01B3 appears to be involved in the regulation of serum bilirubin levels in healthy individuals and in some bilirubin-related disorders that are only partially explained by other known gene variants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{palomba_role_2009,

title = {A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population},

author = {Grazia Palomba and Angela Loi and Antonella Uras and Patrizia Fancello and Giovanna Piras and Attilio Gabbas and Antonio Cossu and Mario Budroni and Antonio Contu and Francesco Tanda and Antonio Farris and Sandra Orr{ù} and Carlo Floris and Marina Pisano and Mario Lovicu and Maria Cristina Santona and Gennaro Landriscina and Laura Crisponi and Giuseppe Palmieri and Maria Monne},

doi = {10.1186/1471-2407-9-245},

issn = {1471-2407},

year  = {2009},

date = {2009-07-01},

journal = {BMC cancer},

volume = {9},

pages = {245},

abstract = {BACKGROUND: In recent years, numerous studies have assessed the prevalence of germline mutations in BRCA1 and BRCA2 genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of BRCA1-2 mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of BRCA1-2 germline mutations was also evaluated. 

METHODS: Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for BRCA1-2 mutations by DHPLC analysis and DNA sequencing. Association of BRCA1 and BRCA2 mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test. 

RESULTS AND CONCLUSION: Overall, 8 BRCA1 and 5 BRCA2 deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in BRCA2 gene. The geographical distribution of BRCA1-2 mutations was related to three specific large areas of Sardinia, reflecting its ancient history: a) the Northern area, linguistically different from the rest of the island (where a BRCA2 c.8764_8765delAG mutation with founder effect was predominant); b) the Middle area, land of the ancient Sardinian population (where BRCA2 mutations are still more common than BRCA1 mutations); and c) the South-Western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of BRCA1-2 germline mutations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{barrett_genome-wide_2009,

title = {Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.},

author = {Barrett, Jeffrey C. and Clayton, David G. and Concannon, Patrick and Akolkar, Beena and Cooper, Jason D. and Erlich, Henry A. and Julier, Cecile and Morahan, Grant and Nerup, Jorn and Nierras, Concepcion and Plagnol, Vincent and Pociot, Flemming and Schuilenburg, Helen and Smyth, Deborah J. and Stevens, Helen and Todd, John A. and Walker, Neil M. and Rich, Stephen S.},

doi = {10.1038/ng.381},

issn = {1546-1718 1061-4036},

year  = {2009},

date = {2009-06-01},

journal = {Nat Genet},

volume = {41},

number = {6},

pages = {703--707},

abstract = {Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 reference samples. Forty-one distinct genomic locations provided evidence for association with T1D in the meta-analysis (P textless 10(-6)). After excluding previously reported associations, we further tested 27 regions in an independent set of 4,267 cases, 4,463 controls and 2,319 affected sib-pair (ASP) families. Of these, 18 regions were replicated (P textless 0.01; overall P textless 5 x 10(-8)) and 4 additional regions provided nominal evidence of replication (P textless 0.05). The many new candidate genes suggested by these results include IL10, IL19, IL20, GLIS3, CD69 and IL27.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19371217,

title = {RNA analysis of consensus sequence splicing mutations: implications for the diagnosis of Wilson disease},

author = {M. Lovicu and M. B. Lepori and S. Incollu and V. ì and A. Zappu and R. Iorio and M. DÁmbrosi and M. T. Pellecchia and P. Barone and G. Maggiore and S. De Virgiliis and A. Cao and G. Loudianos},

year  = {2009},

date = {2009-04-13},

urldate = {2009-04-13},

journal = {Genet Test Mol Biomarkers},

volume = {13},

number = {2},

pages = {185--191},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19179076,

title = {Indolyl-pyrrolone as a new scaffold for Pim1 inhibitors},

year  = {2009},

date = {2009-03-01},

journal = {Bioorg Med Chem Lett},

volume = {19},

number = {5},

pages = {1512--1516},

abstract = {Pim1 belongs to a family of serine/threonine kinases, which is involved in the control of cell growth, differentiation, and apoptosis. Pim1 plays a pivotal role in cytokine signaling and is implicated in the development of a large number of tumors, representing a very attractive target for anticancer therapy. In this work, we applied a virtual screening protocol aimed at identifying small molecules able to inhibit Pim1 activity. The search of novel inhibitors was performed through a structure-based molecular modeling approach, taking advantage of the availability of the three-dimensional crystal structure of inhibitors bound to Pim1. Starting from the knowledge of protein-ligand complexes, the software LigandScout was used to generate pharmacophoric models, in turn used as queries to perform a virtual screening of databases, followed by docking experiments. As a result, a restricted set of candidates for biological testing was identified. Finally, among the six compounds selected as potential inhibitors of Pim1, two candidates endowed with a significant activity against Pim1 emerged. Interestingly, one of these compounds has a chemical scaffold different from inhibitors previously identified.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18996922,

title = {Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to ĐNA},

author = {E Revenkova and M L Focarelli and L Susani and M Paulis and M T Bassi and L Mannini and A Frattini and D Delia and I Krantz and P Vezzoni and R Jessberger and A Musio},

year  = {2009},

date = {2009-02-01},

journal = {Hum Mol Genet},

volume = {18},

number = {3},

pages = {418--427},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19179314,

title = {Gene therapy for immunodeficiency due to adenosine deaminase deficiency},

year  = {2009},

date = {2009-01-01},

journal = {N Engl J Med},

volume = {360", 

 Number="5},

pages = {447--458},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19652199,

title = {Integration of retroviral vectors induces minor changes in the transcriptional activity of Ŧ cells from AĐA-SCIĐ patients treated with gene therapy},

author = {B Cassani and E Montini and G Maruggi and A Ambrosi and M Mirolo and S Selleri and E Biral and I Frugnoli and V Hernandez-Trujillo and C Di Serio and M G Roncarolo and L Naldini and F Mavilio and A Aiuti},

year  = {2009},

date = {2009-01-01},

journal = {Blood},

volume = {114},

number = {17},

pages = {3546--3556},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19542187,

title = {A computational procedure to identify significant overlap of differentially expressed and genomic imbalanced regions in cancer datasets},

author = {S Bicciato and R Spinelli and M Zampieri and E Mangano and F Ferrari and L Beltrame and I Cifola and C Peano and A Solari and C Battaglia},

year  = {2009},

date = {2009-01-01},

journal = {Nucleic Acids Res},

volume = {37},

number = {15},

pages = {5057--5070},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19303062,

title = {Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations},

author = { T. Tanaka and P. Scheet and B. Giusti and S. Bandinelli and M. G. Piras and G. Usala and S. Lai and A. Mulas and A. M. Corsi and A. Vestrini and F. Sofi and A. M. Gori and R. Abbate and J. Guralnik and A. Singleton and G. R. Abecasis and D. Schlessinger and M. Uda and L. Ferrucci},

year  = {2009},

date = {2009-01-01},

volume = {84},

number = {4},

pages = {477--482},

abstract = {The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated with coronary heart disease, stroke and neurological disease. To investigate genetic factors that affect circulating vitamin B6, vitamin B12, folate and homocysteine, a genome-wide association analysis was conducted in the InCHIANTI (N = 1175), SardiNIA (N = 1115), and BLSA (N = 640) studies. The top loci were replicated in an independent sample of 687 participants in the Progetto Nutrizione study. Polymorphisms in the ALPL gene (rs4654748},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{tarasov_col4a1_2009,

title = {COL4A1 is associated with arterial stiffness by genome-wide association scan.},

author = {Tarasov, Kirill V. and Sanna, Serena and Scuteri, Angelo and Strait, James B. and Orru, Marco and Parsa, Afshin and Lin, Ping-I. and Maschio, Andrea and Lai, Sandra and Piras, Maria Grazia and Masala, Marco and Tanaka, Toshiko and Post, Wendy and O'Connell, Jeffrey R. and Schlessinger, David and Cao, Antonio and Nagaraja, Ramaiah and Mitchell, Braxton D. and Abecasis, Goncalo R. and Shuldiner, Alan R. and Uda, Manuela and Lakatta, Edward G. and Najjar, Samer S.},

doi = {10.1161/CIRCGENETICS.108.823245},

issn = {1942-3268 1942-3268},

year  = {2009},

date = {2009-01-01},

journal = {Circ Cardiovasc Genet},

volume = {2},

number = {2},

pages = {151--158},

abstract = {BACKGROUND: Pulse wave velocity (PWV), a noninvasive index of central arterial stiffness, is a potent predictor of cardiovascular mortality and morbidity. Heritability and linkage studies have pointed toward a genetic component affecting PWV. We conducted a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) associated with PWV. METHODS AND RESULTS: The study cohort included participants from the SardiNIA study for whom PWV measures were available. Genotyping was performed in 4221 individuals, using either the Affymetrix 500K or the Affymetrix 10K mapping array sets (with imputation of the missing genotypes). Associations with PWV were evaluated using an additive genetic model that included age, age(2), and sex as covariates. The findings were tested for replication in an independent internal Sardinian cohort of 1828 individuals, using a custom chip designed to include the top 43 nonredundant SNPs associated with PWV. Of the loci that were tested for association with PWV, the nonsynonymous SNP rs3742207 in the COL4A1 gene on chromosome 13 and SNP rs1495448 in the MAGI1 gene on chromosome 3 were successfully replicated (P=7.08 x 10(-7) and P=1.06 x 10(-5), respectively, for the combined analyses). The association between rs3742207 and PWV was also successfully replicated (P=0.02) in an independent population, the Old-Order Amish, leading to an overall P=5.16 x 10(-8). CONCLUSIONS: A genome-wide association study identified a SNP in the COL4A1 gene that was significantly associated with PWV in 2 populations. Collagen type 4 is the major structural component of basement membranes, suggesting that previously unrecognized cell-matrix interactions may exert an important role in regulating arterial stiffness.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zoledziewska2009,

title = {Variation within the CLEC16A gene shows consistent disease association with both multiple sclerosis and type 1 diabetes in Sardinia.},

author = {Zoledziewska, M and Costa, G and Pitzalis, M and Cocco, E and Melis, C and Moi, L and Zavattari, P and Murru, R and Lampis, R and Morelli, L and Poddie, F and Frongia, P and Pusceddu, P and Bajorek, M and Marras, A and Satta, A M and Chessa, A and Pugliatti, M and Sotgiu, S and Whalen, M B and Rosati, G and Cucca, F and Marrosu, M G},

url = {http://www.nature.com/doifinder/10.1038/gene.2008.84 http://www.ncbi.nlm.nih.gov/pubmed/18946483},

doi = {10.1038/gene.2008.84},

issn = {1476-5470},

year  = {2009},

date = {2009-01-01},

journal = {Genes and immunity},

volume = {10},

number = {1},

pages = {15--7},

abstract = {Variation within intron 19 of the CLEC16A (KIAA0350) gene region was recently found to be unequivocally associated with type 1 diabetes (T1D) in genome-wide association (GWA) studies in Northern European populations. A variant in intron 22 that is nearly independent of the intron 19 variant showed suggestive evidence of association with multiple sclerosis (MS). Here, we genotyped the rs725613 polymorphism, representative of the earlier reported associations with T1D within CLEC16A, in 1037 T1D cases, 1498 MS cases and 1706 matched controls, all from the founder, autoimmunity-prone Sardinian population. In these Sardinian samples, allele A of rs725613 is positively associated not only with T1D (odds ratio=1.15, P one-tail=5.1 x 10(-3)) but also, and with a comparable effect size, with MS (odds ratio=1.21, P one-tail 6.7 x 10(-5)). Taken together these data provide evidence of joint disease association in T1D and MS within CLEC16A and underline a shared disease pathway.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nucaro_familial_2008,

title = {Familial translocation t(3;10) (p26.3;p12.31) leading to trisomy 10p12.31-->pter and monosomy 3p26.3-->pter in seven members},

author = {Anna Lisa Nucaro and Marta Meloni and Tiziana Pisano and Paola Melis and Elena Rossi and Rossano Rossino and Simona Corona and Mario Loi and Francesco Achena and Orsetta Zuffardi and Carlo Cianchetti},

doi = {10.1002/ajmg.a.32590},

issn = {1552-4833},

year  = {2008},

date = {2008-12-01},

journal = {American Journal of Medical Genetics. Part A},

volume = {146A},

number = {24},

pages = {3242--3245},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18925640,

title = {Cell fusion is a physiological process in mouse liver},

author = {F Faggioli and M G Sacco and L Susani and C Montagna and P Vezzoni},

year  = {2008},

date = {2008-11-01},

journal = {Hepatology},

volume = {48},

number = {5},

pages = {1655--1664},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18606301,

title = {Ħuman osteoclast-poor osteopetrosis with hypogammaglobulinemia due to ŦNFRSF11A (RANK) mutations},

author = {M M Guerrini and C Sobacchi and B Cassani and M Abinun and S S Kilic and A Pangrazio and D Moratto and E Mazzolari and J Clayton-Smith and P Orchard and F P Coxon and M H Helfrich and J C Crockett and D Mellis and A Vellodi and I Tezcan and L D Notarangelo and M J Rogers and P Vezzoni and A Villa and A Frattini},

year  = {2008},

date = {2008-07-01},

volume = {83},

number = {1},

pages = {64--76},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{noauthor_refining_2008,

title = {Refining genetic associations in multiple sclerosis.},

doi = {10.1016/S1474-4422(08)70122-4},

issn = {1474-4422 1474-4422},

year  = {2008},

date = {2008-07-01},

journal = {Lancet Neurol},

volume = {7},

number = {7},

pages = {567--569},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18514160,

title = {Phosphodiesterase 8B gene variants are associated with serum ŦSH levels and thyroid function},

author = { },

year  = {2008},

date = {2008-06-01},

volume = {82},

number = {6},

pages = {1270--1280},

abstract = {Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over a life span. By genotyping 362,129 SNPs in 4,300 Sardinians, we identified a strong association (p = 1.3 x 10(-11)) between alleles of rs4704397 and circulating TSH levels; each additional copy of the minor A allele was associated with an increase of 0.13 muIU/ml in TSH. The single-nucleotide polymorphism (SNP) is located in intron 1 of PDE8B, encoding a high-affinity cAMP-specific phosphodiesterase. The association was replicated in 4,158 individuals, including additional Sardinians and two genetically distant cohorts from Tuscany and the Old Order Amish (overall p value = 1.9 x 10(-20)). In addition to association of TSH levels with SNPs in PDE8B, our genome scan provided evidence for association with PDE10A and several biologically interesting candidates in a focused analysis of 24 genes. In particular, we found evidence for association of TSH levels with SNPs in the THRB (rs1505287},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18462698,

title = {Pbx1 regulates self-renewal of long-term hematopoietic stem cells by maintaining their quiescence},

author = {F Ficara and M J Murphy and M Lin and M L Cleary},

year  = {2008},

date = {2008-05-01},

journal = {Cell Stem Cell},

volume = {2},

number = {5},

pages = {484--496},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zoledziewska2008-oq,

title = {Further evidence of a primary, causal association of the  PTPN22 620W variant with type 1 diabetes},

author = {Magdalena Zoledziewska and Chiara Perra and Valeria Orr`u and Loredana Moi and Paola Frongia and Mauro Congia and Nunzio Bottini and Francesco Cucca},

doi = {10.2337/db07-0289},

year  = {2008},

date = {2008-01-01},

urldate = {2008-01-01},

journal = {Diabetes},

volume = {57},

number = {1},

pages = {229--234},

publisher = {Ämerican Diabetes Association},

abstract = {ÖBJECTIVE: The minor allele of the nonsynonymous single 

 nucleotide polymorphism (SNP) +1858C>T within the PTPN22 gene is 

 positively associated with type 1 diabetes and other autoimmune 

 diseases. Genetic and functional data underline its causal 

 effect, but some studies suggest that this polymorphism does not 

 entirely explain disease association of the PTPN22 region. The 

 aim of this study was to evaluate type 1 diabetes association 

 within this gene in the Sardinian population. RESEARCH DESIGN 

 AND METHODS: We resequenced the exons and potentially relevant 

 portions of PTPN22 and detected 24 polymorphisms (23 SNPs and 1 

 deletion insertion polymorphism [DIP]), 8 of which were novel. A 

 representative set of 14 SNPs and the DIP were sequentially 

 genotyped and assessed for disease association in 794 families, 

 490 sporadic patients, and 721 matched control subjects. 

 RESULTS: The +1858C>T variant, albeit rare in the general 

 Sardinian population (allele frequency 0.014), was positively associated with type 1 diabetes (P(one tail) = 3.7 x 10(-3)). In 

 contrast, the background haplotype in which this mutation 

 occurred was common (haplotype frequency 0.117) and neutrally 

 associated with disease. We did not confirm disease associations 

 reported in other populations for non +1858C>T variants 

 (rs2488457, rs1310182, and rs3811021), although they were 

 present in appreciable frequencies in Sardinia. Additional weak 

 disease associations with rare variants were detected in the 

 Sardinian families but not confirmed in independent case-control 

 sample sets and are most likely spurious. CONCLUSIONS: We 

 provide further evidence that the +1858C>T polymorphism is 

 primarily associated with type 1 diabetes and exclude major 

 contributions from other purportedly relevant variants within 

 this gene."},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18218852,

title = {Altered intracellular and extracellular signaling leads to impaired Ŧ-cell functions in AĐA-SCIĐ patients},

author = {B Cassani and M Mirolo and F Cattaneo and U Benninghoff and M Hershfield and F Carlucci and A Tabucchi and C Bordignon and M G Roncarolo and A Aiuti},

year  = {2008},

date = {2008-01-01},

journal = {Blood},

volume = {111},

number = {8},

pages = {4209--4219},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{contu_y-chromosome_2008,

title = {Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans.},

author = {Contu, Daniela and Morelli, Laura and Santoni, Federico and Foster, Jamie W. and Francalacci, Paolo and Cucca, Francesco},

doi = {10.1371/journal.pone.0001430},

issn = {1932-6203 1932-6203},

year  = {2008},

date = {2008-01-01},

journal = {PLoS One},

volume = {3},

number = {1},

pages = {e1430},

abstract = {The island of Sardinia shows a unique high incidence of several autoimmune diseases with multifactorial inheritance, particularly type 1 diabetes and multiple sclerosis. The prior knowledge of the genetic structure of this population is fundamental to establish the optimal design for association studies in these diseases. Previous work suggested that the Sardinians are a relatively homogenous population, but some reports were contradictory and data were largely based on variants subject to selection. For an unbiased assessment of genetic structure, we studied a combination of neutral Y-chromosome variants, 21 biallelic and 8 short tandem repeats (STRs) in 930 Sardinian males. We found a high degree of interindividual variation but a homogenous distribution of the detected variability in samples from three separate regions of the island. One haplogroup, I-M26, is rare or absent outside Sardinia and is very common (0.37 frequency) throughout the island, consistent with a founder effect. A Bayesian full likelihood analysis (BATWING) indicated that the time from the most recent common ancestor (TMRCA) of I-M26, was 21.0 (16.0-25.5) thousand years ago (KYA) and that the population began to expand 14.0 (7.8-22.0) KYA. These results suggest a largely pre-Neolithic settlement of the island with little subsequent gene flow from outside populations. Consequently, Sardinia is an especially attractive venue for case-control genome wide association scans in common multifactorial diseases. Concomitantly, the high degree of interindividual variation in the current population facilitates fine mapping efforts to pinpoint the aetiologic polymorphisms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pitzalis_genetic_2008,

title = {Genetic loci linked to type 1 diabetes and multiple sclerosis families in Sardinia.},

author = {Pitzalis, Maristella and Zavattari, Patrizia and Murru, Raffaele and Deidda, Elisabetta and Zoledziewska, Magdalena and Murru, Daniela and Moi, Loredana and Motzo, Costantino and Orru, Valeria and Costa, Gianna and Solla, Elisabetta and Fadda, Elisabetta and Schirru, Lucia and Melis, Maria Cristina and Lai, Marina and Mancosu, Cristina and Tranquilli, Stefania and Cuccu, Stefania and Rolesu, Marcella and Secci, Maria Antonietta and Corongiu, Daniela and Contu, Daniela and Lampis, Rosanna and Nucaro, Annalisa and Pala, Gavino and Pacifico, Adolfo and Maioli, Mario and Frongia, Paola and Chessa, Margherita and Ricciardi, Rossella and Lostia, Stanislao and Marinaro, Anna Maria and Milia, Anna Franca and Landis, Novella and Zedda, Maria Antonietta and Whalen, Michael B. and Santoni, Federico and Marrosu, Maria Giovanna and Devoto, Marcella and Cucca, Francesco},

doi = {10.1186/1471-2350-9-3},

issn = {1471-2350 1471-2350},

year  = {2008},

date = {2008-01-01},

journal = {BMC Med Genet},

volume = {9},

pages = {3},

abstract = {BACKGROUND: The Mediterranean island of Sardinia has a strikingly high incidence of the autoimmune disorders Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). Furthermore, the two diseases tend to be co-inherited in the same individuals and in the same families. These observations suggest that some unknown autoimmunity variant with relevant effect size could be fairly common in this founder population and could be detected using linkage analysis. METHODS: To search for T1D and MS loci as well as any that predispose to both diseases, we performed a whole genome linkage scan, sequentially genotyping 593 microsatellite marker loci in 954 individuals distributed in 175 Sardinian families. In total, 413 patients were studied; 285 with T1D, 116 with MS and 12 with both disorders. Model-free linkage analysis was performed on the genotyped samples using the Kong and Cox logarithm of odds (LOD) score statistic. RESULTS: In T1D, aside from the HLA locus, we found four regions showing a lod-score textgreater or =1; 1p31.1, 6q26, 10q21.2 and 22q11.22. In MS we found three regions showing a lod-score textgreater or =1; 1q42.2, 18p11.21 and 20p12.3. In the combined T1D-MS scan for shared autoimmunity loci, four regions showed a LOD textgreater1, including 6q26, 10q21.2, 20p12.3 and 22q11.22. When we typed more markers in these intervals we obtained suggestive evidence of linkage in the T1D scan at 10q21.2 (LOD = 2.1), in the MS scan at 1q42.2 (LOD = 2.5) and at 18p11.22 (LOD = 2.6). When all T1D and MS families were analysed jointly we obtained suggestive evidence in two regions: at 10q21.1 (LOD score = 2.3) and at 20p12.3 (LOD score = 2.5). CONCLUSION: This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zoledziewska2008,

title = {Further evidence of a primary, causal association of the PTPN22 620W variant with type 1 diabetes.},

author = {Zoledziewska, Magdalena and Perra, Chiara and Orr{ù}, Valeria and Moi, Loredana and Frongia, Paola and Congia, Mauro and Bottini, Nunzio and Cucca, Francesco},

url = {http://diabetes.diabetesjournals.org/cgi/doi/10.2337/db07-0289 http://www.ncbi.nlm.nih.gov/pubmed/17934143},

doi = {10.2337/db07-0289},

issn = {1939-327X},

year  = {2008},

date = {2008-01-01},

journal = {Diabetes},

volume = {57},

number = {1},

pages = {229--34},

abstract = {OBJECTIVE The minor allele of the nonsynonymous single nucleotide polymorphism (SNP) +1858C>T within the PTPN22 gene is positively associated with type 1 diabetes and other autoimmune diseases. Genetic and functional data underline its causal effect, but some studies suggest that this polymorphism does not entirely explain disease association of the PTPN22 region. The aim of this study was to evaluate type 1 diabetes association within this gene in the Sardinian population. RESEARCH DESIGN AND METHODS We resequenced the exons and potentially relevant portions of PTPN22 and detected 24 polymorphisms (23 SNPs and 1 deletion insertion polymorphism [DIP]), 8 of which were novel. A representative set of 14 SNPs and the DIP were sequentially genotyped and assessed for disease association in 794 families, 490 sporadic patients, and 721 matched control subjects. RESULTS The +1858C>T variant, albeit rare in the general Sardinian population (allele frequency 0.014), was positively associated with type 1 diabetes (P(one tail) = 3.7 x 10(-3)). In contrast, the background haplotype in which this mutation occurred was common (haplotype frequency 0.117) and neutrally associated with disease. We did not confirm disease associations reported in other populations for non +1858C>T variants (rs2488457, rs1310182, and rs3811021), although they were present in appreciable frequencies in Sardinia. Additional weak disease associations with rare variants were detected in the Sardinian families but not confirmed in independent case-control sample sets and are most likely spurious. CONCLUSIONS We provide further evidence that the +1858C>T polymorphism is primarily associated with type 1 diabetes and exclude major contributions from other purportedly relevant variants within this gene.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{murru_cri_2008,

title = {Cri du chat mosaicism: an unusual case of partial deletion and partial deletion/ duplication of the short arm of chromosome 5, leading to an unusual cri du chat phenotype.},

author = {D Murru and L Boccone and M S Ristaldi and A L Nucaro},

url = {http://www.ncbi.nlm.nih.gov/pubmed/19239081},

issn = {1015-8146},

year  = {2008},

date = {2008-01-01},

journal = {Genetic counseling (Geneva, Switzerland)},

volume = {19},

number = {4},

pages = {381--6},

abstract = {The Cri du Chat Syndrome (CdCS) is one of the most common deletion syndromes, involving the short arm of chromosome 5, with an incidence of 1 in 50.000 live births. The following are the characteristic features of this syndrome: microcephaly, hypertelorism, round face, micrognatia, epicanthic folds, prominent nasal bridge, hypotonia and severe psychomotor retardation. Patients also show a high pitched cry similar to the mewing of a cat. Deletions and duplications of chromosome 5p have been described in the literature. Mosaicism represents only 3% of this cytogenetic aberration. Up to date, only cases of de novo 5p mosaic anomalies involving two or three rearranged cell lines, with deletions and duplications, have been described. Herein, we report the first case of a patient affected by multiple congenital anomalies and a mosaicism, with two rearranged cell lines: one with a 5p deletion; the other with a 5p deletion/duplication. Our patient did not show the characteristic features described in patients with 5p duplications, but a phenotype compatible with the CdCS. Our case represents the first description of a mosaicism with deletion and deletion/duplication of a portion of the short arm of chromosome 5.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{schirru_genetic_2007,

title = {Genetic testing improves the diagnosis of adult type hypolactasia in the Mediterranean population of Sardinia.},

author = {Schirru, E. and Corona, V. and Usai-Satta, P. and Scarpa, M. and Oppia, F. and Loriga, F. and Cucca, F. and De Virgiliis, S. and Rossino, R. and Macis, M. Doloretta and Jores, R.-D. and Congia, M.},

doi = {10.1038/sj.ejcn.1602638},

issn = {0954-3007 0954-3007},

year  = {2007},

date = {2007-10-01},

journal = {Eur J Clin Nutr},

volume = {61},

number = {10},

pages = {1220--1225},

abstract = {OBJECTIVE: Recently, the C/T-13910 polymorphism on chromosome 2q21 in North-European populations has been found completely associated with lactase activity and its genetic typing proposed as first-stage screening test for adult hypolactasia. However, the C/T-13910 variant in some sub-Saharan African groups is not a predictor of lactase persistence. In this work, we wanted to verify if in the Mediterranean island of Sardinia, located in Southern Europe, the C/T-13910 polymorphism may be useful or not for the diagnosis of adult type hypolactasia. DESIGN: Validation study of a genetic testing for adult type hypolactasia in Sardinians. SETTING: Brotzu Hospital and Microcitemico Hospital, Cagliari, Italy. SUBJECTS: The sample consisted in 84 Sardinian individuals (63 women and 21 men; range 20-73 years) selected from a group of 832 patients. METHODS: Genetic testing was compared to an improved test obtained by a combination of different breath hydrogen tests and clinical assessment. RESULTS: We found that all 49 individuals with lactose malabsorption, demonstrated by a combination of different breath hydrogen tests and clinical assessment, carried the C/C-13910 genotype associated with lactase non-persistence, 23 individuals with lactose normal absorption carried the C/T-13910 genotype associated with lactase persistence and only one person with the above phenotype showed a discordant C/C-13910 genotype. The genetic testing showed very high sensitivity, specificity, positive and negative predictive values of 100, 95.8, 98 and 100%, respectively. CONCLUSIONS: Sardinians, unlike some ethnic groups in sub-Saharan Africa, show the same genetic association of hypolactasia with the C/T-13910 variant as other North-European populations. The genetic testing for the C/T-13910 variant may contribute to improving the diagnosis of adult type hypolactasia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}