@article{zavattari_transmission-ratio_2000,

title = {Transmission-ratio distortion at Xp11.4-p21.1 in type 1 diabetes.},

author = {Zavattari, P. and Esposito, L. and Nutland, S. and Todd, J. A. and Cucca, F.},

doi = {10.1086/302701},

issn = {0002-9297 0002-9297},

year  = {2000},

date = {2000-01-01},

journal = {Am J Hum Genet},

volume = {66},

number = {1},

pages = {330--332},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid10570147,

title = {Genetic dissection of dome formation in a mammary cell line: identification of two genes with opposing action},

author = {I Zucchi and C Montagna and L Susani and R Montesano and M Affer and S Zanotti and E Redolfi and P Vezzoni and R Dulbecco},

year  = {1999},

date = {1999-11-01},

journal = {Proc Natl Acad Sci U S A},

volume = {96},

number = {24},

pages = {13766--13770},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{dalfonso_linkage_1999,

title = {Linkage analysis of multiple sclerosis with candidate region markers in Sardinian and Continental Italian families.},

author = {D'Alfonso, S. and Nistico, L. and Zavattari, P. and Marrosu, M. G. and Murru, R. and Lai, M. and Massacesi, L. and Ballerini, C. and Gestri, D. and Salvetti, M. and Ristori, G. and Bomprezzi, R. and Trojano, M. and Liguori, M. and Gambi, D. and Quattrone, A. and Fruci, D. and Cucca, F. and Richiardi, P. M. and Tosi, R.},

doi = {10.1038/sj.ejhg.5200301},

issn = {1018-4813 1018-4813},

year  = {1999},

date = {1999-04-01},

journal = {Eur J Hum Genet},

volume = {7},

number = {3},

pages = {377--385},

abstract = {Previous genome screens in multiple sclerosis have shown some evidence of linkage in scattered chromosomal regions. Although in no case the evidence of each single study was compelling and although in general the linkage 'peaks' of the different studies did not coincide, some regions can be considered likely candidates for the presence of MS risk genes because of the clustering of MLS scores and homology with eae loci. We performed a linkage analysis of markers in these regions and of intragenic markers of some individual candidate genes (HLA-DRB1,},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{esposito_genetic_1998,

title = {Genetic analysis of chromosome 2 in type 1 diabetes: analysis of putative loci IDDM7, IDDM12, and IDDM13 and candidate genes NRAMP1 and IA-2 and the interleukin-1 gene cluster. IMDIAB Group.},

author = {Esposito, L. and Hill, N. J. and Pritchard, L. E. and Cucca, F. and Muxworthy, C. and Merriman, M. E. and Wilson, A. and Julier, C. and Delepine, M. and Tuomilehto, J. and Tuomilehto-Wolf, E. and Ionesco-Tirgoviste, C. and Nistico', L. and Buzzetti, R. and Pozzilli, P. and Ferrari, M. and Bosi, E. and Pociot, F. and Nerup, J. and Bain, S. C. and Todd, J. A.},

issn = {0012-1797 0012-1797},

year  = {1998},

date = {1998-11-01},

journal = {Diabetes},

volume = {47},

number = {11},

pages = {1797--1799},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cucca1998a,

title = {Investigation of linkage of chromosome 8 to type 1 diabetes: multipoint analysis and exclusion mapping of human chromosome 8 in 593 affected sib-pair families from the U.K. and U.S.},

author = {Cucca, F and Esposito, L and Goy, J V and Merriman, M E and Wilson, A J and Reed, P W and Bain, S C and Todd, J A},

url = {http://www.ncbi.nlm.nih.gov/pubmed/9726245},

issn = {0012-1797},

year  = {1998},

date = {1998-09-01},

journal = {Diabetes},

volume = {47},

number = {9},

pages = {1525--7},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Marrosu1998,

title = {DRB1-DQA1-DQB1 loci and multiple sclerosis predisposition in the Sardinian population.},

author = {Marrosu, M G and Murru, M R and Costa, G and Murru, R and Muntoni, F and Cucca, F},

url = {http://www.ncbi.nlm.nih.gov/pubmed/9668164},

issn = {0964-6906},

year  = {1998},

date = {1998-08-01},

journal = {Human molecular genetics},

volume = {7},

number = {8},

pages = {1235--7},

abstract = {Multiple sclerosis (MS) is a common neurological disease caused by genetic and environmental factors. Previous genetic analyses have suggested that theMHC/HLA region on chromosome 6p21 contains an MS-predisposing component. Which of the many genes present in this region is primarily responsible for disease susceptibility is still an open issue. In this study, we evaluated, in a large cohort of MS families from the Mediterranean island of Sardinia, the role of allelic variation at the HLA-DRB1, DQA1 and DQB1 candidate loci in MS predisposition. Using the transmission disequilibrium test (TDT), we found significant evidence of association with MS in both the Sardinian-specific DRB1*0405(DR4)- DQA1*0501-DQB1*0301 haplotype and the DRB1* 0301(DR3)-DQA1*0501-DQB1*0201 haplotype. Detailed comparative analysis of the DRB1-DQA1- DQB1 haplotypes present in this data set did not identify an individual locus that could explain MS susceptibility. The predisposing effect is haplotype specific, in that it is confined to specific combinations of alleles at the DRB1, DQA1 and DQB1 loci. Cross-ethnic comparison between the two HLA haplotypes associated with MS in Sardinians and the DRB1*1501 (DR2)-DQA1*0102-DQB1* 0602 haplotype, associated with MS in other Caucasian populations, failed to identify any shared epitopes in the DR and DQ molecules that segregated with disease susceptibility. These results suggest that another MHC gene(s), in linkage disequilibrium with specific HLA-DRB1, DQA1, DQB1 haploypes, might be primarily responsible for genetic susceptibility to MS. Alternatively, the presence of complex interactions between different HLA haplotypes, other non-HLA predisposing genes and environmental factors may explain different associations in different populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nakagawa_fine_1998,

title = {Fine mapping of the diabetes-susceptibility locus, IDDM4, on chromosome 11q13.},

author = {Nakagawa, Y. and Kawaguchi, Y. and Twells, R. C. and Muxworthy, C. and Hunter, K. M. and Wilson, A. and Merriman, M. E. and Cox, R. D. and Merriman, T. and Cucca, F. and McKinney, P. A. and Shield, J. P. and Tuomilehto, J. and Tuomilehto-Wolf, E. and Ionesco-Tirgoviste, C. and Nistico, L. and Buzzetti, R. and Pozzilli, P. and Joner, G. and Thorsby, E. and Undlien, D. E. and Pociot, F. and Nerup, J. and Ronningen, K. S. and Bain, S. C. and Todd, J. A.},

issn = {0002-9297 0002-9297},

year  = {1998},

date = {1998-08-01},

journal = {Am J Hum Genet},

volume = {63},

number = {2},

pages = {547--556},

abstract = {Genomewide linkage studies of type 1 diabetes (or insulin-dependent diabetes mellitus [IDDM]) indicate that several unlinked susceptibility loci can explain the clustering of the disease in families. One such locus has been mapped to chromosome 11q13 (IDDM4). In the present report we have analyzed 707 affected sib pairs, obtaining a peak multipoint maximum LOD score (MLS) of 2.7 (lambda(s)=1.09) with linkage (MLStextgreater=0.7) extending over a 15-cM region. The problem is, therefore, to fine map the locus to permit structural analysis of positional candidate genes. In a two-stage approach, we first scanned the 15-cM linked region for increased or decreased transmission, from heterozygous parents to affected siblings in 340 families, of the three most common alleles of each of 12 microsatellite loci. One of the 36 alleles showed decreased transmission (50% expected, 45.1% observed [P=.02, corrected P=.72]) at marker D11S1917. Analysis of an additional 1,702 families provided further support for negative transmission (48%) of D11S1917 allele 3 to affected offspring and positive transmission (55%) to unaffected siblings (test of heterogeneity P=3x10-4, corrected P=. 01]). A second polymorphic marker, H0570polyA, was isolated from a cosmid clone containing D11S1917, and genotyping of 2,042 families revealed strong linkage disequilibrium between the two markers (15 kb apart), with a specific haplotype, D11S1917*03-H0570polyA*02, showing decreased transmission (46.4%) to affected offspring and increased transmission (56.6%) to unaffected siblings (test of heterogeneity P=1.5x10-6, corrected P=4.3x10-4). These results not only provide sufficient justification for analysis of the gene content of the D11S1917 region for positional candidates but also show that, in the mapping of genes for common multifactorial diseases, analysis of both affected and unaffected siblings is of value and that both predisposing and nonpredisposing alleles should be anticipated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cucca1998,

title = {A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3-positive patients.},

author = {Cucca, F and Goy, J V and Kawaguchi, Y and Esposito, L and Merriman, M E and Wilson, A J and Cordell, H J and Bain, S C and Todd, J A},

url = {http://www.nature.com/doifinder/10.1038/995 http://www.ncbi.nlm.nih.gov/pubmed/9662410},

doi = {10.1038/995},

issn = {1061-4036},

year  = {1998},

date = {1998-07-01},

journal = {Nature genetics},

volume = {19},

number = {3},

pages = {301--2},

abstract = {It is generally assumed that the male:female (M:F) ratio in patients with type 1 (insulin-dependent) diabetes mellitus (IDDM) is 1. A recent survey, however, revealed that high incidence countries (mainly European) have a high M:F ratio and low incidence ones (Asian and African) have a low M:F ratio. We have now analysed the M:F ratio according to genotype at the major locus, the major histocompatibility complex (MHC; IDDM1). There are two main IDDM1 susceptibility haplotypes, HLA-DR3 and -DR4, which are present in 95% of Caucasian cases. We report here that in medium/high incidence Caucasian populations from the United States of America, United Kingdom and Sardinia (1307 cases), the bias in male incidence is largely restricted to the DR3/X category of patients (X not = DR4) with a M:F ratio of 1.7 (P=9.3x10(-7)), compared with a ratio of 1.0 in the DR4/Y category (Y;DR3). This is additional evidence for significant heterogeneity between the aetiology of 'DR4-associated' and 'DR3-associated' diabetes. We analysed linkage of type 1 diabetes to chromosome X, and as expected, most of the linkage to Xp13-p11 was in the DR3/X affected sibpair families (n=97; peak multipoint MLS at DXS1068=3.5},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{mein_search_1998,

title = {A search for type 1 diabetes susceptibility genes in families from the United Kingdom.},

author = {Mein, C. A. and Esposito, L. and Dunn, M. G. and Johnson, G. C. and Timms, A. E. and Goy, J. V. and Smith, A. N. and Sebag-Montefiore, L. and Merriman, M. E. and Wilson, A. J. and Pritchard, L. E. and Cucca, F. and Barnett, A. H. and Bain, S. C. and Todd, J. A.},

doi = {10.1038/991},

issn = {1061-4036 1061-4036},

year  = {1998},

date = {1998-07-01},

journal = {Nat Genet},

volume = {19},

number = {3},

pages = {297--300},

abstract = {Genetic analysis of a mouse model of major histocompatability complex (MHC)-associated autoimmune type 1 (insulin-dependent) diabetes mellitus (IDDM) has shown that the disease is caused by a combination of a major effect at the MHC and at least ten other susceptibility loci elsewhere in the genome. A genome-wide scan of 93 affected sibpair families (ASP) from the UK (UK93) indicated a similar genetic basis for human type 1 diabetes, with the major genetic component at the MHC locus (IDDM1) explaining 34% of the familial clustering of the disease (lambda(s)=2.5; refs 3,4). In the present report, we have analysed a further 263 multiplex families from the same population (UK263) to provide a total UK data set of 356 ASP families (UK356). Only four regions of the genome outside IDDM1/MHC, which was still the only major locus detected, were not excluded at lambda(s)=3 and lod=-2, of which two showed evidence of linkage: chromosome 10p13-p11 (maximum lod score (MLS)=4.7},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{villa_partial_1998,

title = {Partial V(D)J recombination activity leads to Omenn syndrome.},

author = {A Villa and S Santagata and F Bozzi and S Giliani and A Frattini and L Imberti and L B Gatta and H D Ochs and K Schwarz and L D Notarangelo and P Vezzoni and E Spanopoulou},

url = {http://www.ncbi.nlm.nih.gov/pubmed/9630231},

issn = {0092-8674},

year  = {1998},

date = {1998-05-01},

journal = {Cell},

volume = {93},

number = {5},

pages = {885--96},

abstract = {Genomic rearrangement of the antigen receptor loci is initiated by the two lymphoid-specific proteins Rag-1 and Rag-2. Null mutations in either of the two proteins abrogate initiation of V(D)J recombination and cause severe combined immunodeficiency with complete absence of mature B and T lymphocytes. We report here that patients with Omenn syndrome, a severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T cells, hypereosinophilia, and high IgE levels, bear missense mutations in either the Rag-1 or Rag-2 genes that result in partial activity of the two proteins. Two of the amino acid substitutions map within the Rag-1 homeodomain and decrease DNA binding activity, while three others lower the efficiency of Rag-1/Rag-2 interaction. These findings provide evidence to indicate that the immunodeficiency manifested in patients with Omenn syndrome arises from mutations that decrease the efficiency of V(D)J recombination.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{merriman_transmission_1998,

title = {Transmission of haplotypes of microsatellite markers rather than single marker alleles in the mapping of a putative type 1 diabetes susceptibility gene (IDDM6).},

author = {Merriman, T. R. and Eaves, I. A. and Twells, R. C. and Merriman, M. E. and Danoy, P. A. and Muxworthy, C. E. and Hunter, K. M. and Cox, R. D. and Cucca, F. and McKinney, P. A. and Shield, J. P. and Baum, J. D. and Tuomilehto, J. and Tuomilehto-Wolf, E. and Ionesco-Tirgoviste, C. and Joner, G. and Thorsby, E. and Undlien, D. E. and Pociot, F. and Nerup, J. and Ronningen, K. S. and Bain, S. C. and Todd, J. A.},

issn = {0964-6906 0964-6906},

year  = {1998},

date = {1998-03-01},

journal = {Hum Mol Genet},

volume = {7},

number = {3},

pages = {517--524},

abstract = {Allelic association methods based on increased transmission of marker alleles will have to be employed for the mapping of complex disease susceptibility genes. However, because the extent of association of single marker alleles with disease is a function of the relative frequency of the allele on disease-associated chromosomes versus non disease-predisposing chromosomes, the most associated marker allele in a region will not necessarily be closest to the disease locus. To overcome this problem we describe a haplotype-based approach developed for mapping of the putative type 1 diabetes susceptibility gene IDDM6. Ten microsatellite markers spanning a 550 kb segment of chromosome 18q21 in the putative IDDM6 region were genotyped in 1708 type 1 diabetic Caucasian families from seven countries. The most likely ancestral diabetogenic chromosome was reconstructed in a stepwise fashion by analysing linkage disequilibrium between a previously defined haplotype of three adjacent markers and the next marker along the chromosome. A plot of transmission from heterozygous parents to affected offspring of single marker alleles present on the ancestral chromosome versus the physical distance between them, was compared with a plot of transmission of haplotypes of groups of three adjacent markers. Analysing transmission of haplotypes largely negated apparent decreases in transmission of single marker alleles. Peak support for association of the D18S487 region with IDDM6 is P = 0.0002 (corrected P = 0.01). The results also demonstrate the utility of polymorphic microsatellite markers to trace and delineate extended and presumably ancient haplotypes in the analysis of common disease and in the search for identical-by-descent chromosome regions that carry an aetiological variant.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid9448288,

title = {Ŧhe rat gene homologous to the human gene 9-27 is involved in the development of the mammary gland},

author = {I Zucchi and C Montagna and L Susani and P Vezzoni and R Dulbecco},

year  = {1998},

date = {1998-02-01},

journal = {Proc Natl Acad Sci U S A},

volume = {95},

number = {3},

pages = {1079--1084},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cucca_male-female_1998,

title = {A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC},

author = {Cucca, F. and Goy, J. V. and Kawaguchi, Y. and Esposito, L. and Merriman, M. E. and Wilson, A. J. and Cordell, H. J. and Bain, S. C. and Todd, J. A.},

doi = {10.1038/995},

issn = {1061-4036 1061-4036},

year  = {1998},

date = {1998-01-01},

journal = {Nat Genet},

volume = {19},

number = {3},

pages = {301--302},

abstract = {It is generally assumed that the male:female (M:F) ratio in patients with type 1 (insulin-dependent) diabetes mellitus (IDDM) is 1. A recent survey, however, revealed that high incidence countries (mainly European) have a high M:F ratio and low incidence ones (Asian and African) have a low M:F ratio. We have now analysed the M:F ratio according to genotype at the major locus, the major histocompatibility complex (MHC; IDDM1). There are two main IDDM1 susceptibility haplotypes, HLA-DR3 and -DR4, which are present in 95% of Caucasian cases. We report here that in medium/high incidence Caucasian populations from the United States of America, United Kingdom and Sardinia (1307 cases), the bias in male incidence is largely restricted to the DR3/X category of patients (X not = DR4) with a M:F ratio of 1.7 (P=9.3x10(-7)), compared with a ratio of 1.0 in the DR4/Y category (Y;DR3). This is additional evidence for significant heterogeneity between the aetiology of 'DR4-associated' and 'DR3-associated' diabetes. We analysed linkage of type 1 diabetes to chromosome X, and as expected, most of the linkage to Xp13-p11 was in the DR3/X affected sibpair families (n=97; peak multipoint MLS at DXS1068=3.5},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cucca_evaluation_1998,

title = {Evaluation of IgA deficiency in Sardinians indicates a susceptibility gene is encoded within the HLA class III region.},

author = {Cucca, F. and Zhu, Z. B. and Khanna, A. and Cossu, F. and Congia, M. and Badiali, M. and Lampis, R. and Frau, F. and De Virgiliis, S. and Cao, A. and Arnone, M. and Piras, P. and Campbell, R. D. and Cooper, M. D. and Volanakis, J. E. and Powis, S. H.},

issn = {0009-9104 0009-9104},

year  = {1998},

date = {1998-01-01},

journal = {Clin Exp Immunol},

volume = {111},

number = {1},

pages = {76--80},

abstract = {IgA deficiency (IgA-D) has been associated with the HLA region, in particular with the North European haplotype HLA-A1, -B8, -DR3, but the exact location of the susceptibility gene(s) is unknown. Some reports suggest that a susceptibility gene is encoded in the class II region, while others implicate the class III region. We exploited differences between the common Sardinian and North European},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{marrosu_multiple_1997,

title = {Multiple sclerosis in Sardinia is associated and in linkage disequilibrium with},

author = {Marrosu, M. G. and Murru, M. R. and Costa, G. and Cucca, F. and Sotgiu, S. and Rosati, G. and Muntoni, F.},

doi = {10.1016/S0002-9297(07)64074-9},

issn = {0002-9297 0002-9297},

year  = {1997},

date = {1997-08-01},

journal = {Am J Hum Genet},

volume = {61},

number = {2},

pages = {454--457},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{merriman_evidence_1997,

title = {Evidence by allelic association-dependent methods for a type 1 diabetes polygene (IDDM6) on chromosome 18q21.},

author = {Merriman, T. and Twells, R. and Merriman, M. and Eaves, I. and Cox, R. and Cucca, F. and McKinney, P. and Shield, J. and Baum, D. and Bosi, E. and Pozzilli, P. and Nistico, L. and Buzzetti, R. and Joner, G. and Ronningen, K. S. and Thorsby, E. and Undlien, D. and Pociot, F. and Nerup, J. and Bain, S. and Barnett, A. and Todd, J.},

issn = {0964-6906 0964-6906},

year  = {1997},

date = {1997-07-01},

journal = {Hum Mol Genet},

volume = {6},

number = {7},

pages = {1003--1010},

abstract = {Type 1 diabetes is a common polygenic disease. Fine mapping of polygenes by affected sibpair linkage analysis is not practical and allelic association or linkage disequilibrium mapping will have to be employed to attempt to detect founder chromosomes. Given prior evidence of linkage of the Jk-D18S64 region of chromosome 18q12-q21 to type 1 diabetes, we evaluated the 12 informative microsatellite markers in the region for linkage with disease by the transmission disequilibrium test (TDT) in a UK data set of type 1 diabetic families (n = 195). Increased transmission of allele 4 of marker D18S487 to affected children was detected (P = 0.02). Support for this was extended in a total of 1067 families from four different countries by isolating, and evaluating by the TDT, two novel microsatellites within 70 kb of D18S487. Evidence for linkage and association was P = 5 x 10(-5) and 3 x 10(-4), respectively. There was no evidence for increased transmission of associated alleles to nonaffected siblings. Analysis of an additional 390 families by the TDT did not extend the evidence further, and reduced support in the total 1457 families to P = 0.001 for linkage and P = 0.003 for association. However, evidence for linkage by affected sibpair allele sharing was strong (P = 3.2 x 10(-5)) in the second data set. Heterogeneity in TDT results between data sets was, in part, accounted for by the presence of more than one common disease-associated haplotype (allelic heterogeneity) which confounds the analysis of individual alleles by the TDT. Guidelines for strategies for the mapping of polygenes are suggested with the emphasis on collections of large numbers of families from multiple populations that should be as genetically homogeneous as possible.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{reed_evidence_1997,

title = {Evidence for a type 1 diabetes susceptibility locus (IDDM10) on human chromosome 10p11-q11.},

author = {Reed, P. and Cucca, F. and Jenkins, S. and Merriman, M. and Wilson, A. and McKinney, P. and Bosi, E. and Joner, G. and Ronningen, K. S. and Thorsby, E. and Undlien, D. and Merriman, T. and Barnett, A. and Bain, S. and Todd, J.},

issn = {0964-6906 0964-6906},

year  = {1997},

date = {1997-07-01},

journal = {Hum Mol Genet},

volume = {6},

number = {7},

pages = {1011--1016},

abstract = {A region of linkage to type 1 diabetes has been defined on human chromosome 10p11-q11 (IDDM10; P = 0.0007) using 236 UK and 76 US affected sibpairs and a 1 cM resolution microsatellite marker map. Analysis by the transmission disequilibrium test (TDT) in 1159 families with at least one diabetic child, from the UK, the US, Norway, Sardinia and Italy provided additional support for linkage at D10S193 (P = 0.006},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid9195958,

title = {hMAF, a small human transcription factor that heterodimerizes specifically with Nrf1 and Nrf2},

author = { M. G. Marini and K. Chan and L. Casula and Y. W. Kan and A. Cao and P. Moi},

year  = {1997},

date = {1997-06-01},

journal = {J Biol Chem},

volume = {272},

number = {26},

pages = {16490--16497},

abstract = {A 1.6-kilobase pair full-length cDNA encoding a transcription factor homologous to the Maf family of proteins was isolated by screening a K562 cDNA library with the NFE2 tandem repeat probe derived from the globin locus control region. The protein, which was designated hMAF, contains a basic DNA binding domain and an extended leucine zipper but lacks any recognizable activation domain. Expressed in vitro, the hMAF protein is able to homodimerize in solution and band-shift the NFE2 tandem repeat probe. In addition to homodimers, hMAF can also form high affinity heterodimers with two members of the NFE2/CNC-bZip family (Nrf1 and Nrf2) but not with a third family member, p45-NFE2. Although hMAF/hMAF homodimers and hMAF/Nrf1 and hMAF/Nrf2 heterodimers bind to the same NFE2 site, they exert functionally opposite effects on the activity of a linked gamma-globin gene. In fact, whereas all hMAF/CNC-bZip heterodimers stimulate the activity of a gamma-promoter reporter construct in K562 cells, the association into homodimers that is induced by overexpressing hMAF inhibits the activity of the same construct. Thus variations in the expression of hMAF may account for the modulation in the activity of the genes that bear NFE2 recognition sites.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Marrosu1997,

title = {Parenteral inheritance of susceptible and protective hla-dr, dq haplotypes in sardinian multiple sclerosis},

author = {Marrosu, M.G., Cucca, F., Murru, R., Costa, G., Murru, M.R., Muntoni, F. },

issn = {03920461},

year  = {1997},

date = {1997-04-01},

journal = {Italian Journal of Neurological Sciences},

volume = {18},

number = {4},

pages = {27},

abstract = {The preponderance of genetic factors in accounting for susceptibility to multiple sclerosis (MS) has recently been demonstrated. Regarding parenteral inheritance, data on MS susceptibility are discordant. Using the transmission-disequilibrium test, we examined maternal and paternal segregation of susceptible and protective HLA-DR,DQ haplotype from 109 MS Sardinian pedigrees. The susceptible DRB1*0405,DQA1*0501,DQB1*0301 haplo-type, found in linkage-disequilium with MS (chi-square=0.001), was inherited by mothers (chi-square=0.001). The protective DRB1*1502,DQA1*0103, DQB1*0603 haplotype, found increased in healthy siblings (chi-square=0.01), was inherited by mothers (chi-square =0.02). These data may suggest an imprinting mechanism in inheritance of HLA alleles involved in MS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{bennett_insulin_1997,

title = {Insulin VNTR allele-specific effect in type 1 diabetes depends on identity of untransmitted paternal allele. The IMDIAB Group.},

author = {Bennett, S. T. and Wilson, A. J. and Esposito, L. and Bouzekri, N. and Undlien, D. E. and Cucca, F. and Nistico, L. and Buzzetti, R. and Bosi, E. and Pociot, F. and Nerup, J. and Cambon-Thomsen, A. and Pugliese, A. and Shield, J. P. and McKinney, P. A. and Bain, S. C. and Polychronakos, C. and Todd, J. A.},

doi = {10.1038/ng1197-350},

issn = {1061-4036 1061-4036},

year  = {1997},

date = {1997-01-01},

journal = {Nat Genet},

volume = {17},

number = {3},

pages = {350--352},

abstract = {The IDDM2 type 1 diabetes susceptibility locus was mapped to and identified as allelic variation at the insulin gene (INS) VNTR regulatory polymorphism. In Caucasians, INS VNTR alleles divide into two discrete size classes. Class I alleles (26 to 63 repeats) predispose in a recessive way to type 1 diabetes, while class III alleles (140 to more than 200 repeats) are dominantly protective. The protective effect may be explained by higher levels of class III},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{congia_hla_1996,

title = {HLA class II genes in chronic hepatitis C virus-infection and associated immunological disorders.},

author = {Congia, M. and Clemente, M. G. and Dessi, C. and Cucca, F. and Mazzoleni, A. P. and Frau, F. and Lampis, R. and Cao, A. and Lai, M. E. and De Virgiliis, S.},

doi = {10.1002/hep.510240603},

issn = {0270-9139 0270-9139},

year  = {1996},

date = {1996-12-01},

journal = {Hepatology},

volume = {24},

number = {6},

pages = {1338--1341},

abstract = {To investigate the factors that may confer susceptibility or protection to hepatitis C virus (HCV) infection and to HCV-associated immunological disorders, we designed two studies on 420 Sardinian transfusion-dependent thalassemia patients followed in our department in Cagliari since 1974. The first one was an epidemiological survey aimed to evaluate the prevalence of HCV infection and},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{davies_saturation_1996,

title = {Saturation multipoint linkage mapping of chromosome 6q in type 1 diabetes.},

author = {Davies, J. L. and Cucca, F. and Goy, J. V. and Atta, Z. A. and Merriman, M. E. and Wilson, A. and Barnett, A. H. and Bain, S. C. and Todd, J. A.},

issn = {0964-6906 0964-6906},

year  = {1996},

date = {1996-07-01},

journal = {Hum Mol Genet},

volume = {5},

number = {7},

pages = {1071--1074},

abstract = {Linkage analysis of type 1 diabetes sib pair families (n = 334) has suggested two separate regions of human chromosome 6q are linked to disease (designated IDDM5 and IDDM8). To test if these are false positive results, all available sib pair families (n = 429) were typed using a 92% informative map of chromosome 6q and multipoint analysis. The two regions still showed positive evidence of linkage, most notably the proterminal region, 6q27, corresponding to IDDM8 (MLS = 2.57},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{bennett_iddm2-vntr-encoded_1996,

title = {IDDM2-VNTR-encoded susceptibility to type 1 diabetes: dominant protection and parental transmission of alleles of the insulin gene-linked minisatellite locus.},

author = {Bennett, S. T. and Wilson, A. J. and Cucca, F. and Nerup, J. and Pociot, F. and McKinney, P. A. and Barnett, A. H. and Bain, S. C. and Todd, J. A.},

doi = {10.1006/jaut.1996.0057},

issn = {0896-8411 0896-8411},

year  = {1996},

date = {1996-06-01},

journal = {J Autoimmun},

volume = {9},

number = {3},

pages = {415--421},

abstract = {IDDM2-encoded predisposition to type 1 diabetes has recently been mapped to the minisatellite or variable number of tandem repeat (VNTR) locus upstream of the insulin and insulin-like growth factor II genes on human chromosome 11p15.5. In a UK case-control study (n = 228 sporadic diabetics; n = 441 healthy controls), we show here that the genotype homozygous for VNTR class I alleles is predisposing to disease (RR = 2.68), and VNTR class III alleles are dominantly protective (RR = 0.37). In 722 diabetic families from the UK (n = 356), USA (n = 173), Denmark (n = 55) and Sardinia (n = 138), we have analysed the transmission of class I alleles to diabetic offspring from class I/III heterozygous parents. We confirm that in families from the USA, class I alleles are transmitted preferentially from fathers. However, in family data sets from the UK, Denmark and Sardinia, the reverse is true and maternal transmission is stronger. Furthermore, in the UK family data set, the difference between maternal and paternal transmissions is significant (P textless 0.05). It is therefore unlikely that 'maternal imprinting' alone explains the parent-of-origin effects in IDDM2-encoded predisposition to type 1 diabetes, at least not in the UK. There is a relationship between VNTR class (allele length) and insulin gene expression, though some results from different studies are conflicting. In the human adult cadaveric pancreas, we confirm our preliminary results that class III alleles are associated with lower levels of insulin mRNA in vivo. Similar results have been obtained independently in human foetal pancreas samples. It is difficult to explain how these marginally lower levels of insulin expression could account for the observed VNTR class},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{davies_linkage_1996,

title = {Linkage of chromosome 6 and type 1 diabetes.},

author = {Davies, J. L. and Cucca, F. and Goy, J. V. and Atta, Z. A. and Merriman, M. E. and Wilson, A. and Barnett, A. H. and Bain, S. C. and Todd, J. A.},

issn = {1042-5179 1026-7913},

year  = {1996},

date = {1996-01-01},

journal = {DNA Seq},

volume = {7},

number = {1},

pages = {25--26},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{macchi_mutations_1995,

title = {Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)},

author = {P Macchi and A Villa and S Giliani and M G Sacco and A Frattini and F Porta and A G Ugazio and J A Johnston and F Candotti and J J O'Shea},

doi = {10.1038/377065a0},

issn = {0028-0836},

year  = {1995},

date = {1995-09-01},

journal = {Nature},

volume = {377},

number = {6544},

pages = {65--68},

abstract = {Severe combined immune deficiency (SCID) represents a heterogenous group of hereditary diseases. Mutations in the common gamma-chain (gamma c), which is part of several cytokine receptors including those for interleukin (IL)-2, IL-4, IL-7, IL-9 and IL-15, are responsible for X-linked SCID, which is usually associated with a lack of circulating T cells and the presence of B lymphocytes (T- B+ SCID). The gene(s) responsible for autosomal recessive T- B+ SCID is still unknown. The Jak-3 protein kinase has been found to associate with the gamma c-chain-containing cytokine receptors. Therefore Jak-3 or other STAT proteins with which it interacts are candidate genes for autosomal recessive T- B+ SCID. Here we investigate two unrelated T- B+ SCID patients (both from consanguineous parents) who have homozygous mutations in the gene for Jak-3. One patient carries a mutation (Tyr100-->Cys) in a conserved tyrosine residue in the JH7 domain of Jak-3 which is absent in more than 150 investigated chromosomes. The other patient carries a homozygous 151-base-pair deletion in the kinase-like domain, leading to a frameshift and premature termination. Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cucca1995,

title = {The distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci.},

author = {Cucca, F and Lampis, R and Frau, F and Macis, D and Angius, E and Masile, P and Chessa, M and Frongia, P and Silvetti, M and Cao, A and {De Virgiliis}, S and Congia, M},

url = {http://www.ncbi.nlm.nih.gov/pubmed/7499178},

issn = {0198-8859},

year  = {1995},

date = {1995-08-01},

journal = {Human immunology},

volume = {43},

number = {4},

pages = {301--8},

abstract = {The contribution of genetic variation at HLA class II loci to the susceptibility to and protection from IDDM was investigated by analyzing the distribution of HLA-DRB1*04 haplotypes in 630 Sardinian newborns and 155 Sardinian IDDM patients. The different RRs and ARs of the various DR4-DQB1*0302 haplotypes, significantly ranging from the strongly associated DRB1*0405, DQB1*0302 to the protective DRB1*0403, DQB1*0302 haplotypes, provides clearcut evidence that the DRB1 locus is crucial in conferring IDDM predisposition or protection. Also, the DQB1 locus influences IDDM predisposition or protection by restricting the disease-positive association to DRB1*0405 haplotypes carrying the susceptibility DQB1*0302 or DQB1*0201 alleles but not the protective DQB1*0301 allele. Haplotype analysis not only suggests that the DRB1 and DQB1 loci influence IDDM risk in the same way, but also that the HLA-linked protection is "dominant" compared with "susceptibility." These results, obtained from a population with one of the highest IDDM incidences in the world, define more clearly the contribution of the various HLA loci to IDDM protection or susceptibility and allow a more precise calculation of AR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Copeman1995,

title = {Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31–q33},

author = {Copeman, J.B. and Cucca, F. and Hearne, C.M. and Cornall, R.J. and Reed, P.W. and R{ø}nningen, K.S. and Undlien, D.E. and Nistic{ò}, L. and Buzzetti, R. and Tosi, R. and Pociot, F. and Nerup, J. and Corn{é}lis, F. and Barnett, A.H. and Bain, S.C. and Todd, J.A.},

url = {http://www.ncbi.nlm.nih.gov/pubmed/7704030 http://www.nature.com/doifinder/10.1038/ng0195-80},

doi = {10.1038/ng0195-80},

issn = {1061-4036},

year  = {1995},

date = {1995-01-01},

journal = {Nature Genetics},

volume = {9},

number = {1},

pages = {80--85},

abstract = {The role of human chromosome 2 in type 1 diabetes was evaluated by analysing linkage and linkage disequilibrium at 21 microsatellite marker loci, using 348 affected sibpair families and 107 simplex families. The microsatellite D2S152 was linked to, and associated with, disease in families from three different populations. Our evidence localizes a new diabetes susceptibility gene, IDDM7, to within two centiMorgans of D2S152. This places it in a region of chromosome 2q that shows conserved synteny with the region of mouse chromosome 1 containing the murine type 1 diabetes gene, Idd5. These results demonstrate the utility of polymorphic microsatellites for linkage disequilibrium mapping of genes for complex diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cucca_distribution_1995,

title = {The distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci.},

author = {Cucca, F. and Lampis, R. and Frau, F. and Macis, D. and Angius, E. and Masile, P. and Chessa, M. and Frongia, P. and Silvetti, M. and Cao, A. and De Virgiliis, S. and Congia, M.},

issn = {0198-8859 0198-8859},

year  = {1995},

date = {1995-01-01},

journal = {Hum Immunol},

volume = {43},

number = {4},

pages = {301--308},

abstract = {The contribution of genetic variation at HLA class II loci to the susceptibility to and protection from IDDM was investigated by analyzing the distribution of},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid7795648,

title = {X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene},

author = {A Villa and L Notarangelo and P Macchi and E Mantuano and G Cavagni and D Brugnoni and D Strina and M C Patrosso and U Ramenghi and M G Sacco},

year  = {1995},

date = {1995-01-01},

journal = {Nat Genet},

volume = {9},

number = {4},

pages = {414--417},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cucca_insulin-dependent_1994,

title = {Insulin-dependent diabetes mellitus and the major histocompatibility complex peptide transporters TAP1 and TAP2: no association in a population with a high disease incidence.},

author = {Cucca, F. and Congia, M. and Trowsdale, J. and Powis, S. H.},

issn = {0001-2815 0001-2815},

year  = {1994},

date = {1994-10-01},

journal = {Tissue Antigens},

volume = {44},

number = {4},

pages = {234--240},

abstract = {Although many studies have established an association between insulin-dependent diabetes mellitus (IDDM) and the class II region of the human major histocompatibility complex (MHC), it has been difficult to assign susceptibility to a single locus. Recently, two antigen-processing genes, TAP1 and TAP2, have been identified within the region. Previous studies have reached conflicting conclusions as to the role of these genes in IDDM; it is uncertain whether an increased frequency of the allele TAP2A and a concomitant decrease in TAP2B are independent disease associations or secondary to linkage disequilibrium (LD) between TAP2A and HLA-DR3. To further investigate this question, we have characterized TAP1 and TAP2 alleles in 129 IDDM patients from Sardinia, a population with limited genetic heterogeneity and a high disease incidence. When compared to 90 random controls, the only significant difference was a decrease in the minor allele TAP2C in patients. However, when HLA-DR and -DQ matched controls were compared, this difference disappeared. Further analysis suggested that TAP2C was in LD with HLA-DRB1*1401 and subtypes of HLA-DRB1*11, alleles which were not observed in the IDDM population. LD was also observed between other TAP and},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid7833930,

title = {Mutations in the vasopressin V2-receptor gene in three families of Italian descent with nephrogenic diabetes insipidus},

author = { V. Faà and M. L. Ventruto and S. Loche and M. Bozzola and R. Podda and A. Cao and M. C. Rosatelli},

year  = {1994},

date = {1994-09-01},

journal = {Hum Mol Genet},

volume = {3},

number = {9},

pages = {1685--1686},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cucca_hla-dqb1*0305_1994,

title = {HLA-DQB1*0305 and -DQB1*0304 alleles among Sardinians. Evolutionary and practical implications for oligotyping.},

author = {Cucca, F. and Frau, F. and Lampis, R. and Floris, M. and Argiolas, L. and Macis, D. and Cao, A. and De Virgiliis, S. and Congia, M.},

issn = {0198-8859 0198-8859},

year  = {1994},

date = {1994-06-01},

journal = {Hum Immunol},

volume = {40},

number = {2},

pages = {143--149},

abstract = {This study, performed in individuals of Sardinian descent, reports an epidemiologic and molecular analysis of the recently identified DQB1*0304 and DQB1*0305 alleles. These two alleles having a gene frequency of 0.017 and 0.005, respectively, are not uncommon in Sardinia and are distributed fairly uniformly on the island. The analysis of DQB1 second and third exons of the two alleles revealed that although they have always been found included within the same DRB1*0403-DQA1*03 haplotype, they had a different origin. The sequence pattern of DQB1*0305 confirmed that it originated from the DQB1*0302 "recipient" gene by the insertion of a DQB1*0402 nucleotide stretch, within its beta-sheet region, while that of DQB1*0304 suggested that it originated from the DQB1*0301 gene, either by a single point mutation at codon 57 (GCC instead of GAC) or, alternatively, by a segmental transfer of a DQB1*0302 motif, including codon 57, within its alpha-helic region. Independently from the mechanism of generation, the fact that DQB1*0304 originated from DQB1*0301 allele was intriguing considering that, in over 1500 HLA class II Sardinian haplotypes examined, neither the putative parental DRB1*0403-DQA1*03-DQB1*0301 haplotypes were found. Finally, since the assignment of DQB1*0305 may be inaccurate with the traditional panel of probes commonly used for DQB1 oligotyping, the use of an additional oligonucleotide probe is recommended.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{congia_gene_1994,

title = {A gene dosage effect of the DQA1*0501/DQB1*0201 allelic combination influences the clinical heterogeneity of celiac disease.},

author = {Congia, M. and Cucca, F. and Frau, F. and Lampis, R. and Melis, L. and Clemente, M. G. and Cao, A. and De Virgiliis, S.},

issn = {0198-8859 0198-8859},

year  = {1994},

date = {1994-06-01},

journal = {Hum Immunol},

volume = {40},

number = {2},

pages = {138--142},

abstract = {This study reports the HLA-DR and DQ molecular characterization of 62 CD patients of Sardinian descent. Patients were divided in two groups (36 in group I and 26 in group II) according to the clinical features at the disease onset. Among the patients of group I, having the fully expressed form of CD and a mean age of 3 years at disease onset, a significant increase of DRB1*0301, DQA1*0501, DQB1*0201 homozygotes, encoding in cis two DQ (alpha 1*0501, beta 1*0201) susceptibility heterodimers, was observed when compared either with the patients of group II (pIII textless 0.012) or with healthy individuals (pI textless 10(-6)). On the other hand, in the patients of group II, presenting oligosymptomatic forms and a mean age of 5.7 years at the disease onset, the haplotype combinations encoding in cis or in trans only one DQ (alpha 1*0501, beta 1*0201) heterodimer were significantly increased in comparison either with the patients of group I (pIII textless 0.026) or with controls (pII textless 10(-6)). These findings suggest that a double dose of DQA1*0501, DQB1*0201 genes may predispose a person to an earlier onset and to more severe disease manifestations. Genotype analysis showed that only three patients (all in group I) failed to form in trans or in cis the DQ (alpha 1*0501, beta 1*0201) heterodimer and carried the DQA1*0101,DQB1*0501 haplotype, suggesting its possible role in CD susceptibility. In addition, a significant increment of DQB1*0501 gene (pc textless 0.0065) was found comparing the frequency of DQB1 alleles in CD patients and healthy controls, after exclusion of DQB1*0201 chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cucca_combinations_1993,

title = {Combinations of specific DRB1, DQA1, DQB1 haplotypes are associated with insulin-dependent diabetes mellitus in Sardinia.},

author = {Cucca, F. and Muntoni, F. and Lampis, R. and Frau, F. and Argiolas, L. and Silvetti, M. and Angius, E. and Cao, A. and De Virgiliis, S. and Congia, M.},

issn = {0198-8859 0198-8859},

year  = {1993},

date = {1993-06-01},

journal = {Hum Immunol},

volume = {37},

number = {2},

pages = {85--94},

abstract = {The Sardinian population has an extremely high incidence of IDDM (30.2 of 100.000 in the age group of 0-14 years). This study reports the molecular characterization of HLA class II genes in 120 IDDM sporadic patients and 89 healthy subjects of Sardinian origin. Compared with other Caucasians, both Sardinian patients and controls had an unusual distribution of haplotypes and genotypes. In particular, there was a high gene frequency of the DRB1*0301, DQA1*0501, DQB1*0201 susceptibility haplotype both in patients (0.58) and controls (0.23) while a reduction of the DRB1*1501, DQA1*0102, DQB1*0602 protective haplotype (0.03) was observed in the healthy population. This distribution may partially explain the high incidence of IDDM reported in Sardinia. The analysis of the DQ beta 57 and DQ alpha 52 residues showed that the absence of Asp 57 and the presence of Arg 52 were associated with IDDM in a dose-response manner. On the other hand, we found that (a) a very similar distribution of these residues was found when comparing Sardinians with another healthy Caucasian population from the same latitude but with a lower rate of IDDM incidence; (b) several genotypes encoding the identical DQ alpha 52/DQ beta 57 phenotype carried very different relative risks; and (c) the DRB1*0403, DQA1*0301, DQB1*0304 haplotype (DQ beta 57 Asp-neg and DQ alpha 52 Arg-pos) was found in 40% of the DR4-positive controls but not in patients (p = 0.00034), while the DRB1*0405, DQA1*0301, and DQB1*0302 haplotype carrying the same residues at the same positions was found in 70% of the DR4-positive patients and in only one control (p = 0.00003). These findings suggest that IDDM susceptibility cannot be completely explained by the model in which only DQ alpha 52 and DQ beta 57 residues are taken into account.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cucca_novel_1993,

title = {A novel HLA-DQB1 allele: evidence for gene conversion event promoted by chi-like sequence at DQB1 locus.},

author = {Cucca, F. and Muntoni, F. and Lampis, R. and Frau, F. and Cao, A. and De Virgiliis, S. and Congia, M.},

issn = {0001-2815 0001-2815},

year  = {1993},

date = {1993-05-01},

journal = {Tissue Antigens},

volume = {41},

number = {5},

pages = {263--266},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{congia_high_1992,

title = {A high frequency of the A30, B18, DR3, DRw52, DQw2 extended haplotype in Sardinian celiac disease patients: further evidence that disease susceptibility is conferred by DQ A1*0501, B1*0201.},

author = {Congia, M. and Frau, F. and Lampis, R. and Frau, R. and Mele, R. and Cucca, F. and Muntoni, F. and Porcu, S. and Boi, F. and Contu, L.},

issn = {0001-2815 0001-2815},

year  = {1992},

date = {1992-02-01},

journal = {Tissue Antigens},

volume = {39},

number = {2},

pages = {78--83},

abstract = {This study characterizes by serological and molecular methods the HLA class I and class II alleles in a group of celiac disease children, their parents and a control group of Sardinian descent. We found the DR3-DQw2 haplotype in all patients which was, in almost all cases (84%), associated with the HLA-A30, B18, DR3, DRw52, DQw2 extended haplotype named "Sardinian haplotype" because of its frequency (12-15%) in this Caucasian population. This is the first time that this DQw2-linked haplotype has been reported with such a high frequency in CD. However, no different distribution of "Sardinian haplotype" was found comparing CD patients with 91 haplotyped DQw2-positive controls. This finding indicates that the DQw2 antigen in Sardinians is almost always associated with the A30, B18, DR3, DRw52, DQw2 extended haplotype. The DQA1 and DQB1 second exon sequence analysis of the B18,DR3 and B8,DR3 haplotypes showed the DQA1*0501 and DQB1*0201 alleles which shared the already published sequences. DPB1 subtyping showed the DPB1*0301 allele more frequently (p less than 0.005) in CD patients but this difference was no longer significant when patients and controls, both heterozygous for the DR3-DQw2 haplotype, were compared. We suggest that the divergent HLA extended haplotypes and DP allele associated with CD, described in different Caucasian populations, can be explained by the particular DQw2 linkage disequilibrium in each population.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{muntoni_hla_1992,

title = {The HLA DQB1*0502 allele is neutrally associated with insulin-dependent diabetes mellitus in the Sardinian population.},

author = {Muntoni, F. and Congia, M. and Cucca, F. and Cossu, P. and Porcu, S. and Frau, F. and Arnone, M. and Songini, M. and Muntoni, S. and Cao, A.},

issn = {0001-2815 0001-2815},

year  = {1992},

date = {1992-01-01},

journal = {Tissue Antigens},

volume = {39},

number = {5},

pages = {262--265},

abstract = {In the Sardinian population a very high incidence of insulin-dependent diabetes mellitus (IDDM) and the lack of HLA-DR2 protective effect due to the high frequency of the A2, Cw7, B17, 3F31, DR2, DQw1 extended haplotype has been reported. This haplotype, carrying a Serine at position 57 of the DQB1*0502 allele, has been previously reported to be underrepresented in patients when compared to controls. In order to provide an explanation for this finding, we defined by RFLP analysis the HLA haplotype of 45 Sardinian IDDM patients and 49 controls. All DR-2DQw1 subjects were molecularly characterized at the HLA DQA and DQB loci. All DR2-positive patients and the vast majority of the DR2-positive controls had the DQB1*0502 allele at the DR2-linked DQB1 locus, with no statistically significant difference between the two groups. All DQA1 genes were the ones expected, with only two exceptions. Nine out of 10 of the DR2-positive patients were compound heterozygotes for DQB1*0201/DQB1*0502 alleles; only this allele combination was significantly increased (p less than 0.0003). Our data suggests that a) the DQB1*0502 allele is neutral for IDDM development and b) the susceptibility to IDDM in our DR2-positive patients is related to the compound heterozygous state between the neutral DQA1*0102/DQB1*0502 and the susceptibility DQA1*0501/DQB1*0201 alleles.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{muntoni_different_1991,

title = {Different HLA DR2-DQw1 haplotypes in Sardinian and northern Italian populations: implications for multiple sclerosis susceptibility.},

author = {Muntoni, F. and Murru, M. R. and Costa, G. and Congia, M. and Cucca, F. and Cossu, P. and Cao, A. and Dessalvi, L. and Pirastu, M. and Marrosu, M. G.},

issn = {0001-2815 0001-2815},

year  = {1991},

date = {1991-07-01},

journal = {Tissue Antigens},

volume = {38},

number = {1},

pages = {34--36},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{de_virgiliis_deferoxamine-induced_1988,

title = {Deferoxamine-induced growth retardation in patients with thalassemia major.},

author = {De Virgiliis, S. and Congia, M. and Frau, F. and Argiolu, F. and Diana, G. and Cucca, F. and Varsi, A. and Sanna, G. and Podda, G. and Fodde, M.},

issn = {0022-3476 0022-3476},

year  = {1988},

date = {1988-10-01},

journal = {J Pediatr},

volume = {113},

number = {4},

pages = {661--669},

abstract = {In the retrospective study reported here, we compared the longitudinal growth in three groups of children with thalassemia major who received a similar transfusion program but different schedules of chelation treatment. In those patients who initiated deferoxamine (DF) administration by daily subcutaneous infusion (50 to 80 mg/kg/day) simultaneously with the beginning of transfusion (at 8 +/- 6 months), mean height at 2 to 6 years of age was significantly reduced in comparison (1) with those patients who initiated DF subcutaneous treatment after 3 years at similar doses and (2) with those who were treated intramuscularly with small doses. In the patients treated at an early stage, those with more marked stunted growth had a clinical and radiologic ricketslike syndrome associated with joint stiffness. Mineral metabolism studies in these patients showed a reduction of hair and leukocyte zinc levels and leukocyte alkaline phosphatase activity. Our findings indicate that DF administration at high doses by continuous infusion before iron overload has been established adversely affects longitudinal growth. By contrast, after 3 years of age, even large doses (in the order of 100/mg/kg/day) did not result in growth retardation. The growth retardation observed may be related to chelation of other trace elements, including zinc, in the presence of low iron burden, to the direct toxic effect of unchelated DF by interference with critical iron-dependent enzymes, or both. These results indicate that in patients with thalassemia major, DF administration should be initiated only after iron accumulation is established, namely, around 3 years of age, after 20 to 30 transfusions, which are usually associated with ferritin levels in the range of 800 to 1000 ng/ml. At this age, deferoxamine doses should be established on the basis of iron balance studies and dose response curves. Doses higher than 50 to 60 mg/kg do not adversely affect growth but produce toxic side effects on acoustic and visual pathways and therefore should not be used. Longitudinal growth monitoring of DF-treated patients is warranted.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31497877b,

title = {Crisponi/cold-induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts},

author = {Insa Buers and Ivana Persico and Lara Schöning and Yvonne Nitschke and Maja Di Rocco and Angela Loi and Puneet Kaur Sahi and Gulen Eda Utine and Bilge Bayraktar-Tanyeri and Giuseppe Zampino and Giangiorgio Crisponi and Frank Rutsch and Laura Crisponi},

doi = {10.1111/cge.13639},

issn = {1399-0004},

journal = {Clin Genet},

volume = {97},

number = {1},

pages = {209--221},

abstract = {Crisponi/cold-induced sweating syndrome (CS/CISS) is an autosomal recessive disease characterized by hyperthermia, camptodactyly, feeding and respiratory difficulties often leading to sudden death in the neonatal period. The affected individuals who survived the first critical years of life, develop cold-induced sweating and scoliosis in early childhood. The disease is caused by variants in the CRLF1 or in the CLCF1 gene. Both proteins form a heterodimeric complex that acts on cells expressing the ciliary neurotrophic factor receptor (CNTFR). CS/CISS belongs to the family of "CNTFR-related disorders" showing a similar clinical phenotype. Recently, variants in other genes, including KLHL7, NALCN, MAGEL2 and SCN2A, previously linked to other diseases, have been associated with a CS/CISS-like phenotype. Therefore, retinitis pigmentosa and Bohring-Optiz syndrome-like (KLHL7), Congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome (NALCN), Chitayat-Hall/Schaaf-Yang syndrome (MAGEL2), and early infantile epileptic encephalopathy-11 syndrome (SCN2A) all share an overlapping phenotype with CS/CISS, especially in the neonatal period. This review aims to summarize the existing literature on CS/CISS, focusing on the current state of differential diagnosis, pathogenesis and treatment concepts in order to achieve an accurate and rapid diagnosis. This will improve patient management and enable specific treatments for the affected individuals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38981480,

title = {Intestinal Blastocystis is linked to healthier diets and more favorable cardiometabolic outcomes in 56,989 individuals from 32 countries},

author = {Elisa Piperni and Long H Nguyen and Paolo Manghi and Hanseul Kim and Edoardo Pasolli and Sergio Andreu-Sánchez and Alberto Arrè and Kate M Bermingham and Aitor Blanco-Míguez and Serena Manara and Mireia Valles-Colomer and Elco Bakker and Fabio Busonero and Richard Davies and Edoardo Fiorillo and Francesca Giordano and George Hadjigeorgiou and Emily R Leeming and Monia Lobina and Marco Masala and Andrea Maschio and Lauren J McIver and Mauro Pala and Maristella Pitzalis and Jonathan Wolf and Jingyuan Fu and Alexandra Zhernakova and Simone M Cacciò and Francesco Cucca and Sarah E Berry and Danilo Ercolini and Andrew T Chan and Curtis Huttenhower and Tim D Spector and Nicola Segata and Francesco Asnicar},

doi = {10.1016/j.cell.2024.06.018},

issn = {1097-4172},

journal = {Cell},

volume = {187},

number = {17},

pages = {4554--4570.e18},

abstract = {Diet impacts human health, influencing body adiposity and the risk of developing cardiometabolic diseases. The gut microbiome is a key player in the diet-health axis, but while its bacterial fraction is widely studied, the role of micro-eukaryotes, including Blastocystis, is underexplored. We performed a global-scale analysis on 56,989 metagenomes and showed that human Blastocystis exhibits distinct prevalence patterns linked to geography, lifestyle, and dietary habits. Blastocystis presence defined a specific bacterial signature and was positively associated with more favorable cardiometabolic profiles and negatively with obesity (p < 1e-16) and disorders linked to altered gut ecology (p < 1e-8). In a diet intervention study involving 1,124 individuals, improvements in dietary quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings suggest a potentially beneficial role for Blastocystis, which may help explain personalized host responses to diet and downstream disease etiopathogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39076966,

title = {Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination},

author = {Valeria Orrù and Valentina Serra and Michele Marongiu and Sandra Lai and Valeria Lodde and Magdalena Zoledziewska and Maristella Steri and Annalisa Loizedda and Monia Lobina and Maria Grazia Piras and Francesca Virdis and Giuseppe Delogu and Maria Giuseppina Marini and Maura Mingoia and Matteo Floris and Marco Masala and M Paola Castelli and Rafaela Mostallino and Jessica Frau and Lorena Lorefice and Gabriele Farina and Marzia Fronza and Daniele Carmagnini and Elisa Carta and Silvy Pilotto and Paola Chessa and Marcella Devoto and Paolo Castiglia and Paolo Solla and Roberto Ignazio Zarbo and Maria Laura Idda and Maristella Pitzalis and Eleonora Cocco and Edoardo Fiorillo and Francesco Cucca},

doi = {10.3389/fimmu.2024.1416464},

issn = {1664-3224},

journal = {Front Immunol},

volume = {15},

pages = {1416464},

abstract = {INTRODUCTION: Disease-modifying therapies (DMTs) have been shown to improve disease outcomes in multiple sclerosis (MS) patients. They may also impair the immune response to vaccines, including the SARS-CoV-2 vaccine. However, available data on both the intrinsic immune effects of DMTs and their influence on cellular response to the SARS-CoV-2 vaccine are still incomplete.



METHODS: Here, we evaluated the immune cell effects of 3 DMTs on the response to mRNA SARS-CoV-2 vaccination by comparing MS patients treated with one specific therapy (fingolimod, dimethyl fumarate, or natalizumab) with both healthy controls and untreated patients. We profiled 23 B-cell traits, 57 T-cell traits, and 10 cytokines, both at basal level and after stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS patients, treated with DMTs or untreated, and 32 healthy controls. Measurements were made before vaccination and at three time points after immunization.



RESULTS AND DISCUSSION: MS patients treated with fingolimod showed the strongest immune cell dysregulation characterized by a reduction in all measured lymphocyte cell classes; the patients also had increased immune cell activation at baseline, accompanied by reduced specific immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike specific B cells progressively increased over the three time points after vaccination, even when antibodies measured from the same samples instead showed a decline. Our findings demonstrate that repeated booster vaccinations in MS patients are crucial to overcoming the immune cell impairment caused by DMTs and achieving an immune response to the SARS-CoV-2 vaccine comparable to that of healthy controls.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28445677,

title = {Overexpression of the Cytokine BAFF and Autoimmunity Risk},

author = {Maristella Steri and Valeria Orrù and M Laura Idda and Maristella Pitzalis and Mauro Pala and Ilenia Zara and Carlo Sidore and Valeria Faà and Matteo Floris and Manila Deiana and Isadora Asunis and Eleonora Porcu and Antonella Mulas and Maria G Piras and Monia Lobina and Sandra Lai and Mara Marongiu and Valentina Serra and Michele Marongiu and Gabriella Sole and Fabio Busonero and Andrea Maschio and Roberto Cusano and Gianmauro Cuccuru and Francesca Deidda and Fausto Poddie and Gabriele Farina and Mariano Dei and Francesca Virdis and Stefania Olla and Maria A Satta and Mario Pani and Alessandro Delitala and Eleonora Cocco and Jessica Frau and Giancarlo Coghe and Lorena Lorefice and Giuseppe Fenu and Paola Ferrigno and Maria Ban and Nadia Barizzone and Maurizio Leone and Franca R Guerini and Matteo Piga and Davide Firinu and Ingrid Kockum and Izaura Lima Bomfim and Tomas Olsson and Lars Alfredsson and Ana Suarez and Patricia E Carreira and Maria J Castillo-Palma and Joseph H Marcus and Mauro Congia and Andrea Angius and Maurizio Melis and Antonio Gonzalez and Marta E Alarcón Riquelme and Berta M da Silva and Maurizio Marchini and Maria G Danieli and Stefano Del Giacco and Alessandro Mathieu and Antonello Pani and Stephen B Montgomery and Giulio Rosati and Jan Hillert and Stephen Sawcer and Sandra D'Alfonso and John A Todd and John Novembre and Gonçalo R Abecasis and Michael B Whalen and Maria G Marrosu and Alessandra Meloni and Serena Sanna and Myriam Gorospe and David Schlessinger and Edoardo Fiorillo and Magdalena Zoledziewska and Francesco Cucca},

doi = {10.1056/NEJMoa1610528},

issn = {1533-4406},

journal = {N Engl J Med},

volume = {376},

number = {17},

pages = {1615--1626},

abstract = {BACKGROUND: Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways.



METHODS: Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated.



RESULTS: A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria.



CONCLUSIONS: A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24074872b,

title = {Genetic variants regulating immune cell levels in health and disease},

author = {Valeria Orrù and Maristella Steri and Gabriella Sole and Carlo Sidore and Francesca Virdis and Mariano Dei and Sandra Lai and Magdalena Zoledziewska and Fabio Busonero and Antonella Mulas and Matteo Floris and Wieslawa I Mentzen and Silvana A M Urru and Stefania Olla and Michele Marongiu and Maria G Piras and Monia Lobina and Andrea Maschio and Maristella Pitzalis and Maria F Urru and Marco Marcelli and Roberto Cusano and Francesca Deidda and Valentina Serra and Manuela Oppo and Rosella Pilu and Frederic Reinier and Riccardo Berutti and Luca Pireddu and Ilenia Zara and Eleonora Porcu and Alan Kwong and Christine Brennan and Brendan Tarrier and Robert Lyons and Hyun M Kang and Sergio Uzzau and Rossano Atzeni and Maria Valentini and Davide Firinu and Lidia Leoni and Gianluca Rotta and Silvia Naitza and Andrea Angius and Mauro Congia and Michael B Whalen and Chris M Jones and David Schlessinger and Gonçalo R Abecasis and Edoardo Fiorillo and Serena Sanna and Francesco Cucca},

doi = {10.1016/j.cell.2013.08.041},

issn = {1097-4172},

journal = {Cell},

volume = {155},

number = {1},

pages = {242--256},

abstract = {The complex network of specialized cells and molecules in the immune system has evolved to defend against pathogens, but inadvertent immune system attacks on "self" result in autoimmune disease. Both genetic regulation of immune cell levels and their relationships with autoimmunity are largely undetermined. Here, we report genetic contributions to quantitative levels of 95 cell types encompassing 272 immune traits, in a cohort of 1,629 individuals from four clustered Sardinian villages. We first estimated trait heritability, showing that it can be substantial, accounting for up to 87% of the variance (mean 41%). Next, by assessing ∼8.2 million variants that we identified and confirmed in an extended set of 2,870 individuals, 23 independent variants at 13 loci associated with at least one trait. Notably, variants at three loci (HLA, IL2RA, and SH2B3/ATXN2) overlap with known autoimmune disease associations. These results connect specific cellular phenotypes to specific genetic variants, helping to explicate their involvement in disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}