2015
A Rapid, High-Quality, Cost-Effective, Comprehensive and Expandable Targeted Next-Generation Sequencing Assay for Inherited Heart Diseases
Wilson KD, Shen P, Fung E, Karakikes I, Zhang A, InanlooRahatloo K, Odegaard J, Sallam K, Davis RW, Lui GK, Ashley EA, Scharfe C, Wu JC. A Rapid, High-Quality, Cost-Effective, Comprehensive and Expandable Targeted Next-Generation Sequencing Assay for Inherited Heart Diseases. Circulation Research 2015, 117: 603-611. PMID: 26265630, PMCID: PMC4568077, DOI: 10.1161/circresaha.115.306723.Peer-Reviewed Original ResearchConceptsHeterozygous single nucleotide polymorphismsCongenital heart disease genesThousands of mutationsHeart disease genesShelf kitsRegulatory sequencesNext-generation sequencingSingle nucleotide polymorphismsCardiac developmentDisease genesGenomic DNATargeted Next-Generation Sequencing AssayCardiac genesGenesSequencing runPowerful new toolHigh-throughput detectionNucleotide polymorphismsSequencing assaysMutationsMiR-499Polymorphic regionDNA mutation detectionGermline variantsNext-generation sequencing assay
2014
A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system
Schlecht U, Suresh S, Xu W, Aparicio AM, Chu A, Proctor MJ, Davis RW, Scharfe C, St Onge RP. A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system. BMC Genomics 2014, 15: 263. PMID: 24708151, PMCID: PMC4023593, DOI: 10.1186/1471-2164-15-263.Peer-Reviewed Original ResearchConceptsRespiratory growthFunctional screenCopper homeostasis genesHomozygous diploid deletionIntracellular copper concentrationList of genesComplex cellular systemsDeletion strainHomeostasis genesCopper homeostasisLow vacuolar pHDirect regulatorRespiratory defectsDifferent genesAerobic organismsIron uptakeFunctional linkMendelian disordersGenesCellular systemsGrowth mediumVacuolar pHHomeostasis resultsGenetic originHuman health
2011
High-quality DNA sequence capture of 524 disease candidate genes
Shen P, Wang W, Krishnakumar S, Palm C, Chi AK, Enns GM, Davis RW, Speed TP, Mindrinos MN, Scharfe C. High-quality DNA sequence capture of 524 disease candidate genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 6549-6554. PMID: 21467225, PMCID: PMC3080966, DOI: 10.1073/pnas.1018981108.Peer-Reviewed Original ResearchConceptsGenome informationCandidate genomic regionsCopy number differencesHigh GC contentPadlock probesMolecular diagnosticsSingle nucleotide changeExon-level resolutionDisease candidate genesMitochondrial genesGenomic regionsSequence captureOrnithine transcarbamylase deficiencyGC contentOTC geneCandidate genesDNA variantsExon captureGenomic DNANucleotide changesSample processingStructural variantsGenesSequence verificationDNA samples
2010
Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing
Wang W, Shen P, Thiyagarajan S, Lin S, Palm C, Horvath R, Klopstock T, Cutler D, Pique L, Schrijver I, Davis RW, Mindrinos M, Speed TP, Scharfe C. Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing. Nucleic Acids Research 2010, 39: 44-58. PMID: 20843780, PMCID: PMC3017602, DOI: 10.1093/nar/gkq750.Peer-Reviewed Original ResearchConceptsDNA variantsFunctional DNA variantsMitochondrial DNA maintenanceRare DNA variantsSecond-generation sequencing technologiesNovel rare variantsSanger capillary sequencingSynergistic genetic effectsNuclear candidate genesDNA maintenanceRare variantsGenomic variationSequencing technologiesRare heterozygous variantsCandidate genesGenetic effectsFalse discovery rateMitochondrial disordersCapillary sequencingSequence verificationGenesNovel statistical methodSequencingDiscovery rateHeterozygous variants
2009
Mapping Gene Associations in Human Mitochondria using Clinical Disease Phenotypes
Scharfe C, Lu HH, Neuenburg JK, Allen EA, Li GC, Klopstock T, Cowan TM, Enns GM, Davis RW. Mapping Gene Associations in Human Mitochondria using Clinical Disease Phenotypes. PLOS Computational Biology 2009, 5: e1000374. PMID: 19390613, PMCID: PMC2668170, DOI: 10.1371/journal.pcbi.1000374.Peer-Reviewed Original ResearchConceptsMitochondrial disease genesDisease genesMitochondrial genesMost mitochondrial proteinsMitochondrial disease phenotypesGene network analysisDisease phenotypePhenotypic featuresGenotype-phenotype relationsNuclear genesHuman mitochondriaMitochondrial proteinsCharacteristic interaction patternsPhenotypic dataCandidate genesMitochondrial systemDifferent genesSimilar phenotypeGene associationsGenesFunctional interactionMitochondrial disordersClinical disease phenotypeSimilarity valuesPhenotype
2006
MitoP2: the mitochondrial proteome database—now including mouse data
Prokisch H, Andreoli C, Ahting U, Heiss K, Ruepp A, Scharfe C, Meitinger T. MitoP2: the mitochondrial proteome database—now including mouse data. Nucleic Acids Research 2006, 34: d705-d711. PMID: 16381964, PMCID: PMC1347489, DOI: 10.1093/nar/gkj127.Peer-Reviewed Original ResearchConceptsMitochondrial proteinsSystematic genome-wide studiesMitochondrial proteome databaseNovel mitochondrial proteinGenome-wide studiesSystems biology approachOrthologous proteinsMolecular functionsBiology approachProteome databaseRare mitochondrial diseaseMitochondrial diseasePhenotype screeningMitochondrial dysfunctionReference proteinProteinMitochondriaMouse dataMitoP2ProteomicsIntegration of dataYeastGenesSpeciesPathway
2005
Identifying new candidate genes for hereditary facial paresis on chromosome 3q21–q22 by RNA in situ hybridization in mouse
van der Zwaag B, Burbach JP, Scharfe C, Oefner PJ, Brunner HG, Padberg GW, van Bokhoven H. Identifying new candidate genes for hereditary facial paresis on chromosome 3q21–q22 by RNA in situ hybridization in mouse. Genomics 2005, 86: 55-67. PMID: 15953540, DOI: 10.1016/j.ygeno.2005.03.007.Peer-Reviewed Original ResearchConceptsHereditary congenital facial paresisNew candidate genesMouse developmentCandidate genesSitu hybridizationTranscription-PCR analysisUndetectable expression levelsMouse embryogenesisPositional candidatesExpression analysisUbiquitous expressionGenesMeans of RNAExpression levelsGenetic defectsRNADisease familiesHybridizationCongenital cranial dysinnervation disordersExpressionFacial paresisCranial dysinnervation disordersEmbryogenesisChromosomesFamily
2003
Role of duplicate genes in genetic robustness against null mutations
Gu Z, Steinmetz LM, Gu X, Scharfe C, Davis RW, Li WH. Role of duplicate genes in genetic robustness against null mutations. Nature 2003, 421: 63-66. PMID: 12511954, DOI: 10.1038/nature01198.Peer-Reviewed Original ResearchConceptsDuplicate genesGenetic robustnessNull mutationSevere fitness effectsGenome-wide evaluationAlternative metabolic pathwaysFitness effectsLoss of functionSequence similarityRegulatory networksDeletion mutantsS. cerevisiaeGenesMetabolic pathwaysDuplicate copiesGene deletionFunctional compensationFitness dataCopiesMutationsMutantsCerevisiaeRelative importanceOrganismsSecond mechanism
2002
Systematic screen for human disease genes in yeast
Steinmetz LM, Scharfe C, Deutschbauer AM, Mokranjac D, Herman ZS, Jones T, Chu AM, Giaever G, Prokisch H, Oefner PJ, Davis RW. Systematic screen for human disease genes in yeast. Nature Genetics 2002, 31: 400-404. PMID: 12134146, DOI: 10.1038/ng929.Peer-Reviewed Original ResearchConceptsMitochondrial proteinsNuclear-encoded mitochondrial proteinsGenomic map positionFunctional genomic studiesHuman disease genesGene expression analysisHuman mitochondriaYeast deletionHuman orthologGenomic studiesMap positionHuman genesSystematic screenFunctional screenStrain fitnessExpression analysisDisease genesHuman disordersMitochondrial diseaseHigh similarityMitochondrial respirationHeritable diseaseMitochondrial functionGenesProtein
2000
The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein
Pusch C, Zeitz C, Brandau O, Pesch K, Achatz H, Feil S, Scharfe C, Maurer J, Jacobi F, Pinckers A, Andreasson S, Hardcastle A, Wissinger B, Berger W, Meindl A. The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein. Nature Genetics 2000, 26: 324-327. PMID: 11062472, DOI: 10.1038/81627.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceBrainChromosome MappingDNA Mutational AnalysisDNA, ComplementaryElectroretinographyEye ProteinsFemaleGene Expression ProfilingGenesGenetic HeterogeneityGenetic MarkersGlycosylphosphatidylinositolsHumansKidneyLeucineMaleModels, MolecularMolecular Sequence DataMultigene FamilyMuscle ProteinsMusclesNerve Tissue ProteinsNight BlindnessOrgan SpecificityPedigreeProtein ConformationProteoglycansRepetitive Sequences, Amino AcidRetinaReverse Transcriptase Polymerase Chain ReactionSequence DeletionSequence Homology, Amino AcidTestisX ChromosomeConceptsLeucine-rich repeatsLeucine-rich repeat proteinFuture functional analysisProtein-protein interactionsCell-cell contactProximal short armCongenital stationary night blindnessGenetic mappingNew genesX chromosome2Repeat proteinsExtracellular proteinsLinkage intervalFunctional analysisStationary night blindnessDifferent lociShort armCell adhesionAmino acidsGenesCSNB1 locusProteinDifferent mutationsLociMutation analysis
1999
MITOP: database for mitochondria-related proteins, genes and diseases
Scharfe C, Zaccaria P, Hoertnagel K, Jaksch M, Klopstock T, Lill R, Prokisch H, Gerbitz K, Mewes HW, Meitinger T. MITOP: database for mitochondria-related proteins, genes and diseases. Nucleic Acids Research 1999, 27: 153-155. PMID: 9847163, PMCID: PMC148118, DOI: 10.1093/nar/27.1.153.Peer-Reviewed Original ResearchConceptsGene catalogProtein entriesMitochondrial-encoded genesMitochondria-related proteinsCaenorhabditis elegansProtein catalogueEST hitsMitochondrial processesNeurospora crassaFASTA searchInterspecies homologyMus musculusReference sequenceHomologyGenesProteinFacilitate investigationProtein abnormalitiesSequenceElegansCrassaCerevisiaeMusculusSpeciesPathway