Publications (27) View all
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Article: Genome-wide significant association of ANKRD55 rs6859219 and multiple sclerosis risk.
Journal of Medical Genetics 01/2013; · 6.36 Impact Factor -
Article: Mitochondrial haplogroup H correlates with ATP levels and age at onset in Huntington disease.
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ABSTRACT: Mitochondrial dysfunction has been implicated in the pathogenesis of Huntington disease (HD), a primarily neurodegenerative disorder that results from an expansion in the polymorphic trinucleotide CAG tract in the HD gene. In order to evaluate whether mitochondrial DNA (mtDNA) variation contributes to HD phenotype we genotyped 13 single nucleotide polymorphisms (SNPs) that define the major European mtDNA haplogroups in 404 HD patients. Genotype-dependent functional effects on intracellular ATP concentrations were assessed in peripheral leukocytes. In patients carrying the most common haplogroup H (48.3%), we demonstrate a significantly lower age at onset (AO). In combination with PGC-1 alpha genotypes, 3.8% additional residual variance in HD AO can be explained. Intracellular ATP concentrations in HD patients carrying the cytochrome c oxidase subunit I (CO1) 7028C allele defining haplogroup H were significantly higher in comparison to non-H individuals (mean +/- SEM, 599 +/- 51.8 ng/ml, n = 14 vs. 457.5 +/- 40.4 ng/ml, p = 0.03, n = 9). In contrast, ATP concentrations in cells of HD patients independent from mtDNA haplogroup showed no significant differences in comparison to matched healthy controls. Our data suggest that an evolutionarily advantageous mitochondrial haplogroup is associated with functional mitochondrial alterations and may modify disease phenotype in the context of neurodegenerative conditions such as HD.Journal of Molecular Medicine 04/2010; 88(4):431-6. · 4.67 Impact Factor -
Article: Progressive retinal atrophy in Schapendoes dogs: mutation of the newly identified CCDC66 gene.
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ABSTRACT: Canine generalized progressive retinal atrophy (gPRA) is characterized by continuous degeneration of photoreceptor cells leading to night blindness and progressive vision loss. Until now, mutations in 11 genes have been described that account for gPRA in dogs, mostly following an autosomal recessive inheritance mode. Here, we describe a gPRA locus comprising the newly identified gene coiled-coil domain containing 66 (CCDC66) on canine chromosome 20, as identified via linkage analysis in the Schapendoes breed. Mutation screening of the CCDC66 gene revealed a 1-bp insertion in exon 6 leading to a stop codon as the underlying cause of disease. The insertion is present in all affected dogs in the homozygous state as well as in all obligatory mutation carriers in the heterozygous state. The CCDC66 gene is evolutionarily conserved in different vertebrate species and exhibits a complex pattern of differential RNA splicing resulting in various isoforms in the retina. Immunohistochemically, CCDC66 protein is detected mainly in the inner segments of photoreceptors in mouse, dog, and man. The affected Schapendoes retina lacks CCDC66 protein. Thus this natural canine model for gPRA yields superior potential to understand functional implications of this newly identified protein including its physiology, and it opens new perspectives for analyzing different aspects of the general pathophysiology of gPRA.Neurogenetics 09/2009; 11(2):163-74. · 3.35 Impact Factor -
Article: Analysis of variation in the IL7RA and IL2RA genes in atopic dermatitis.
Journal of dermatological science 07/2009; 55(2):138-40. · 3.71 Impact Factor -
Article: Genomic NGFB variation and multiple sclerosis in a case control study.
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ABSTRACT: Nerve growth factor beta (NGFB) is involved in cell proliferation and survival, and it is a mediator of the immune response. ProNGF, the precursor protein of NGFB, has been shown to induce cell death via interaction with the p75 neurotrophin receptor. In addition, this neurotrophin is differentially expressed in males and females. Hence NGFB is a good candidate to influence the course of multiple sclerosis (MS), much like in the murine model of experimental autoimmune encephalomyelitis (EAE). Ten single nucleotide polymorphisms (SNPs) were genotyped in the NGFB gene in up to 1120 unrelated MS patients and 869 controls. Expression analyses were performed for selected MS patients in order to elucidate the possible functional relevance of the SNPs. Significant association of NGFB variations with MS is evident for two SNPs. NGFB mRNA seems to be expressed in sex- and disease progression-related manner in peripheral blood mononuclear cells. NGFB variation and expression levels appear as modulating factors in the development of MS.BMC Medical Genetics 01/2009; 9:107. · 2.33 Impact Factor
