Johansen A

References (3)

Title : Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders - Novarino_2014_Science_343_506
Author(s) : Novarino G , Fenstermaker AG , Zaki MS , Hofree M , Silhavy JL , Heiberg AD , Abdellateef M , Rosti B , Scott E , Mansour L , Masri A , Kayserili H , Al-Aama JY , Abdel-Salam GMH , Karminejad A , Kara M , Kara B , Bozorgmehri B , Ben-Omran T , Mojahedi F , El Din Mahmoud IG , Bouslam N , Bouhouche A , Benomar A , Hanein S , Raymond L , Forlani S , Mascaro M , Selim L , Shehata N , Al-Allawi N , Bindu PS , Azam M , Gunel M , Caglayan A , Bilguvar K , Tolun A , Issa MY , Schroth J , Spencer EG , Rosti RO , Akizu N , Vaux KK , Johansen A , Koh AA , Megahed H , Durr A , Brice A , Stevanin G , Gabriel SB , Ideker T , Gleeson JG
Ref : Science , 343 :506 , 2014
Abstract : Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.
ESTHER : Novarino_2014_Science_343_506
PubMedSearch : Novarino_2014_Science_343_506
PubMedID: 24482476

Title : Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes - Torsvik_2010_Hum.Genet_127_55
Author(s) : Torsvik J , Johansson S , Johansen A , Ek J , Minton J , Raeder H , Ellard S , Hattersley A , Pedersen O , Hansen T , Molven A , Njolstad PR
Ref : Hum Genet , 127 :55 , 2010
Abstract : We have previously shown that heterozygous single-base deletions in the carboxyl-ester lipase (CEL) gene cause exocrine and endocrine pancreatic dysfunction in two multigenerational families. These deletions were found in the first and fourth repeats of a variable number of tandem repeats (VNTR), which has proven challenging to sequence due to high GC-content and considerable length variation. We have therefore developed a screening method consisting of a multiplex PCR followed by fragment analysis. The method detected putative disease-causing insertions and deletions in the proximal repeats of the VNTR, and determined the VNTR-length of each allele. When blindly testing 56 members of the two families with known single-base deletions in the CEL VNTR, the method correctly assessed the mutation carriers. Screening of 241 probands from suspected maturity-onset diabetes of the young (MODY) families negative for mutations in known MODY genes (95 individuals from Denmark and 146 individuals from UK) revealed no deletions in the proximal repeats of the CEL VNTR. However, we found one Danish patient with a short, novel CEL allele containing only three VNTR repeats (normal range 7-23 in healthy controls). This allele co-segregated with diabetes or impaired glucose tolerance in the patient's family as six of seven mutation carriers were affected. We also identified individuals who had three copies of a complete CEL VNTR. In conclusion, the CEL gene is highly polymorphic, but mutations in CEL are likely to be a rare cause of monogenic diabetes.
ESTHER : Torsvik_2010_Hum.Genet_127_55
PubMedSearch : Torsvik_2010_Hum.Genet_127_55
PubMedID: 19760265
Gene_locus related to this paper: human-CEL

Title : Large-scale studies of the functional K variant of the butyrylcholinesterase gene in relation to Type 2 diabetes and insulin secretion - Johansen_2004_Diabetologia_47_1437
Author(s) : Johansen A , Nielsen EM , Andersen G , Hamid YH , Jensen DP , Glumer C , Drivsholm T , Borch-Johnsen K , Jorgensen T , Hansen T , Pedersen O
Ref : Diabetologia , 47 :1437 , 2004
Abstract : AIMS/HYPOTHESIS: Polymorphisms of the butyrylcholinesterase gene (BCHE) are reported to associate with Alzheimer's disease and a recent study found a significant association of the BCHE K variant (G1615A/Ala539Thr) with Type 2 diabetes. The objectives of our study were to examine whether the BCHE K variant is associated with Type 2 diabetes or estimates of pancreatic beta cell function in large-scale populations of glucose-tolerant Caucasians.
METHODS: The variant was genotyped in association studies comprising a total of 1408 Type 2 diabetic patients and 4935 glucose-tolerant control subjects. Genotype-phenotype studies were carried out in the 4935 glucose-tolerant control subjects.
RESULTS: There was no difference in allele frequency between Type 2 diabetic patients and control subjects (20.3% [95% confidence interval: 18.8-21.8] vs 20.4% [19.6-21.2], non-significant). In the genotype-phenotype studies we found no consistent association with BMI, fasting or post-OGTT plasma glucose, serum insulin or serum C-peptide levels. CONCLUSIONS/INTERPRETATION: The present study does not support the suggestion that the BCHE K polymorphism is associated with Type 2 diabetes or with estimates of pancreatic beta cell function in large-scale Danish Caucasian populations.
ESTHER : Johansen_2004_Diabetologia_47_1437
PubMedSearch : Johansen_2004_Diabetologia_47_1437
PubMedID: 15258737