0000000000970937

AUTHOR

Jennifer C. Schymick

showing 3 related works from this author

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis

2009

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 …

amyotrophic lateral sclerosisLinkage disequilibriumPopulationamyotrophic lateral sclerosis; genetics; GWASingle-nucleotide polymorphismGenome-wide association studyBiologyGWAPolymorphism Single Nucleotide03 medical and health sciences0302 clinical medicineGenotypeGeneticsmedicineHumansPolymorphismAmyotrophic lateral sclerosiseducationMolecular BiologyGenetics (clinical)030304 developmental biologyGenetics0303 health scienceseducation.field_of_studyGenomeSLA wide genome screeningGenome HumanAssociation Studies ArticlesCase-control studySingle NucleotideGeneral MedicineOdds ratiomedicine.diseaseSettore MED/26 - NEUROLOGIAAmyotrophic Lateral Sclerosis; genetics Case-Control Studies Genome; Human Genome-Wide Association Study Humans Polymorphism; Single NucleotideCase-Control Studies030217 neurology & neurosurgeryHumanGenome-Wide Association StudyHuman Molecular Genetics
researchProduct

FUS mutations in sporadic amyotrophic lateral sclerosis

2011

Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease. © 2010 .

AdultMaleAgingAmyotrophic lateral sclerosis; FUS; Italy; Sporadic disease; United States of America;AdolescentGenotypesporadic patientsDNA Mutational AnalysisALS; FUS mutations; sporadic patientsBiologymedicine.disease_causeArticlePathogenesisExonYoung AdultDNA Mutational AnalysisGenotypemedicineHumansFUS mutationsAmyotrophic lateral sclerosisChildGeneAgedGeneticsAged 80 and overMutationGeneral NeuroscienceAmyotrophic Lateral Sclerosisamyotrophic lateral sclerosis FUS geneticsExonsMiddle Agedmedicine.diseaseUnited StatesSettore MED/26 - NEUROLOGIAItalyMutationRNA-Binding Protein FUSFemaleNeurology (clinical)Geriatrics and GerontologyALSDevelopmental BiologyRNA-Binding Protein FUS
researchProduct

Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS

2010

Summary Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein ( VCP ) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS). Mutations in VCP have previously been identified in families with Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD). Screening of VCP in a cohort of 210 familial ALS cases and 78 autopsy-proven ALS cases identified four additional mutations including a p.R155H mutation in a pathologically proven case of ALS. VCP protein is essential for maturation of ubiquitin-containing autophagosomes, and mutant VCP toxicity is partially mediated through its effect on…

Adenosine TriphosphataseMaleCell Cycle ProteinsUBQLN2Cohort Studies0302 clinical medicineReference ValuesValosin Containing ProteinCell Cycle ProteinReference ValueAmyotrophic lateral sclerosisExome sequencingAdenosine TriphosphatasesGenetics0303 health sciencesGeneral NeuroscienceExonsMiddle AgedPedigree3. Good healthMultisystem proteinopathyFemaleSettore MED/26 - NeurologiaCase-Control StudieChromosomes Human Pair 9HumanFrontotemporal dementiaNeuroscience(all)Valosin-containing proteinExonBiologyProtein degradationTARDBPArticle03 medical and health sciencesmedicineHumansAged030304 developmental biologyAmyotrophic lateral sclerosis familial ALS exome sequencingNeuroscience (all)business.industryAmyotrophic Lateral Sclerosismedicine.diseaseAmino Acid SubstitutionCase-Control StudiesMutationbiology.proteinCohort Studiebusiness030217 neurology & neurosurgeryAmyotrophic Lateral SclerosiNeuron
researchProduct