TY  - JOUR
A1  - Kaupmann, Klemens
A1  - Sendtner, Michael
A1  - Stöckli, Kurt A.
A1  - Jockusch, Harald
T1  - The gene of ciliary neurotrophic factor (cntf) maps to murine chromosome 19 and its expression is not affected in the hereditary motoneuron disease 'wobbler' of the mouse
N2  - The cDNA for ciliary neurotrophic factor (CNTF), a polypeptide involved in the survival of motoneurons in mammals, has recently been cloned (Stöckli et al., Nature, 342, 920 - 923, 1989; Lin et al. Science, 246, 1023 - 1025, 1989). We have now localized the corresponding gene Cntf to chromosome 19 in the mouse, using an interspecific cross between Mus spretus and Mus musculus domesticus. The latter was carrying the gene wobbler (wr) for spinal muscular atrophy. DNA was prepared from backcross individuals and typed for the segregation of species-specific Cntf restriction fragments in relation to DNA markers of known chromosomal location. The M.spretus allele of Cntf cosegregated with chromosome 19 markers and mapped closely to Ly-1, to a region of mouse chromosome 19 with conserved synteny to human chromosome 11q. Cntf is not linked to wr, and the expression of CNTF mRNA and protein appears close to normal in facial and sciatic nerves, of affected (wr/wr) mice, suggesting that motoneuron degeneration of wobbler mice has its origin in defects other than reduced CNTF expression.
KW  - Mus spretus
KW  - interspeific backcross
KW  - spinal muscular atrophy
KW  - linkage
KW  - restriction fragment length polymorphism
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-42626
ER  - 
TY  - JOUR
A1  - Galimberti, Daniela
A1  - Dell'Osso, Bernardo
A1  - Fenoglio, Chiara
A1  - Villa, Chiara
A1  - Cortini, Francesca
A1  - Serpente, Maria
A1  - Kittel-Schneider, Sarah
A1  - Weigl, Johannes
A1  - Neuner, Maria
A1  - Volkert, Juliane
A1  - Leonhard, C.
A1  - Olmes, David G.
A1  - Kopf, Juliane
A1  - Cantoni, Claudia
A1  - Ridolfi, Elisa
A1  - Palazzo, Carlotta
A1  - Ghezzi, Laura
A1  - Bresolin, Nereo
A1  - Altamura, A.C.
A1  - Scarpini, Elio
A1  - Reif, Andreas
T1  - Progranulin Gene Variability and Plasma Levels in Bipolar Disorder and Schizophrenia
JF  - PLoS One
N2  - Basing on the assumption that frontotemporal lobar degeneration (FTLD), schizophrenia and bipolar disorder (BPD) might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN) in a German population of patients with schizophrenia (n=271) or BPD (n=237) as compared with 574 age-, gender-and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls. A significantly decreased allelic frequency of the minor versus the wild-type allele was observed for rs2879096 (23.2 versus 34.2%, P<0.001, OR: 0.63, 95% CI: 0.49-0.80), rs4792938 (30.7 versus 39.7%, P=0.005, OR: 0.70, 95% CI: 0.55-0.89) and rs5848 (30.3 versus 36.8, P=0.007, OR: 0.71, 95% CI: 0.56-0.91). Mean +/- SEM progranulin plasma levels were significantly decreased in BPD patients, either Germans or Italians, as compared with controls (89.69 +/- 3.97 and 116.14 +/- 5.80 ng/ml, respectively, versus 180.81 +/- 18.39 ng/ml P<0.001) and were not correlated with age. In conclusion, GRN variability decreases the risk to develop BPD and schizophrenia, and progranulin plasma levels are significantly lower in BPD patients than in controls. Nevertheless, a larger replication analysis would be needed to confirm these preliminary results.
KW  - people
KW  - frontotemporal lobar degeneration
KW  - genome-wide association
KW  - Alzheimers disease
KW  - risk genes
KW  - dementia
KW  - GRN
KW  - mutation
KW  - families
KW  - linkage
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131910
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Kiryluk, Krzysztof
A1  - Yifu, Li
A1  - Sanna-Cherchi, Simone
A1  - Rohanizadegan, Mersedeh
A1  - Suzuki, Hitoshi
A1  - Eitner, Frank
A1  - Snyder, Holly J.
A1  - Choi, Murim
A1  - Hou, Ping
A1  - Scolari, Francesco
A1  - Izzi, Claudia
A1  - Gigante, Maddalena
A1  - Gesualdo, Loreto
A1  - Savoldi, Silvana
A1  - Amoroso, Antonio
A1  - Cusi, Daniele
A1  - Zamboli, Pasquale
A1  - Julian, Bruce A.
A1  - Novak, Jan
A1  - Wyatt, Robert J.
A1  - Mucha, Krzysztof
A1  - Perola, Markus
A1  - Kristiansson, Kati
A1  - Viktorin, Alexander
A1  - Magnusson, Patrik K.
A1  - Thorleifsson, Gudmar
A1  - Thorsteinsdottir, Unnur
A1  - Stefansson, Kari
A1  - Boland, Anne
A1  - Metzger, Marie
A1  - Thibaudin, Lise
A1  - Wanner, Christoph
A1  - Jager, Kitty J.
A1  - Goto, Shin
A1  - Maixnerova, Dita
A1  - Karnib, Hussein H.
A1  - Nagy, Judit
A1  - Panzer, Ulf
A1  - Xie, Jingyuan
A1  - Chen, Nan
A1  - Tesar, Vladimir
A1  - Narita, Ichiei
A1  - Berthoux, Francois
A1  - Floege, Jürgen
A1  - Stengel, Benedicte
A1  - Zhang, Hong
A1  - Lifton, Richard P.
A1  - Gharavi, Ali G.
T1  - Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis
JF  - PLoS Genetics
N2  - IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5x10\(^{-32}\) 3x10\(^{-10}\), with heterogeneity detected only at the PSMB9/TAP1 locus (I\(^{-2}\) = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5x10\(^{-4}\)). A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3x10\(^{-128}\)). This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.
KW  - linkage
KW  - genome-wide association
KW  - multiple sclerosis
KW  - renal disease
KW  - New mexico
KW  - recombination hotspot
KW  - italian population
KW  - natural history
KW  - HLA
KW  - glomerulonephritis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130195
VL  - 8
IS  - 6
ER  - 
TY  - JOUR
A1  - Sadovnick, A. Dessa
A1  - Traboulsee, Anthony L.
A1  - Bernales, Cecily Q.
A1  - Ross, Jay P.
A1  - Forwell, Amanda L.
A1  - Yee, Irene M.
A1  - Guillot-Noel, Lena
A1  - Fontaine, Bertrand
A1  - Cournu-Rebeix, Isabelle
A1  - Alcina, Antonio
A1  - Fedetz, Maria
A1  - Izquierdo, Guillermo
A1  - Matesanz, Fuencisla
A1  - Hilven, Kelly
A1  - Dubois, Bénédicte
A1  - Goris, An
A1  - Astobiza, Ianire
A1  - Alloza, Iraide
A1  - Antigüedad, Alfredo
A1  - Vandenbroeck, Koen
A1  - Akkad, Denis A.
A1  - Aktas, Orhan
A1  - Blaschke, Paul
A1  - Buttmann, Mathias
A1  - Chan, Andrew
A1  - Epplen, Joerg T.
A1  - Gerdes, Lisa-Ann
A1  - Kroner, Antje
A1  - Kubisch, Christian
A1  - Kümpfel, Tania
A1  - Lohse, Peter
A1  - Rieckmann, Peter
A1  - Zettl, Uwe K.
A1  - Zipp, Frauke
A1  - Bertram, Lars
A1  - Lill, Christina M.
A1  - Fernandez, Oscar
A1  - Urbaneja, Patricia
A1  - Leyva, Laura
A1  - Alvarez-Cermeño, Jose Carlos
A1  - Arroyo, Rafael
A1  - Garagorri, Aroa M.
A1  - García-Martínez, Angel
A1  - Villar, Luisa M.
A1  - Urcelay, Elena
A1  - Malhotra, Sunny
A1  - Montalban, Xavier
A1  - Comabella, Manuel
A1  - Berger, Thomas
A1  - Fazekas, Franz
A1  - Reindl, Markus
A1  - Schmied, Mascha C.
A1  - Zimprich, Alexander
A1  - Vilariño-Güell, Carles
T1  - Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients
JF  - G3: Genes Genomes Genetics
N2  - Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.
KW  - multiple sclerosis
KW  - genetics
KW  - linkage
KW  - association
KW  - plasminogen
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165405
VL  - 6
IS  - 7
ER  -