2019
Aberrant splicing contributes to severe α-spectrin-linked congenital hemolytic anemia
Gallagher PG, Maksimova Y, Lezon-Geyda K, Newburger PE, Medeiros D, Hanson RD, Rothman J, Israels S, Wall DA, Sidonio RF, Sieff C, Gowans LK, Mittal N, Rivera-Santiago R, Speicher DW, Baserga SJ, Schulz VP. Aberrant splicing contributes to severe α-spectrin-linked congenital hemolytic anemia. Journal Of Clinical Investigation 2019, 129: 2878-2887. PMID: 31038472, PMCID: PMC6597203, DOI: 10.1172/jci127195.Peer-Reviewed Original ResearchConceptsRecessive hereditary spherocytosisSplice acceptor siteHuman genetic diseasesMRNA stability studiesAberrant splicing contributesSplicing contributesWhole-genome sequencingSplicing analysisHereditary pyropoikilocytosisTermination codonNull allelesGenome sequencingWhole-exome sequencingBranch pointsNumerous mutationsGenetic diseasesLinkage disequilibriumMRNA transcriptsΑ-spectrinMinigene studiesAcceptor sitesMutationsExome sequencingNew targets
2018
Altered Splicing from a Mutated Alternate Branch Point Is Common in Severe Alpha-Spectrin Linked Inherited Anemia
Lezon-Geyda K, Schulz V, Maksimova Y, Gallagher P. Altered Splicing from a Mutated Alternate Branch Point Is Common in Severe Alpha-Spectrin Linked Inherited Anemia. Blood 2018, 132: 503. DOI: 10.1182/blood-2018-99-117752.Peer-Reviewed Original ResearchMRNA transcriptsTermination codonK562 cellsMinigene assayIntron 30Precise genetic basisAcceptor sitesInsertion/deletion mutationsHereditary pyropoikilocytosisWhole-genome sequencingNMD inhibitorsAcceptor splice siteDiagnostic gene panelsGenome databaseMRNA splicingWild-type minigeneConsensus sitesAltered splicingExon 31Genetic basisTranscript productionErythroid cellsGene manipulationGenetic analysisWT backgroundPklr Intron Splicing-Associated Mutations and Alternate Diagnoses Are Common in Pyruvate Kinase Deficient Patients with Single or No Pklr Coding Mutations
Lezon-Geyda K, Rose M, McNaull M, Knoll C, Yaish H, Pastore Y, Fermi E, Glader B, Bianchi P, Grace R, Gallagher P. Pklr Intron Splicing-Associated Mutations and Alternate Diagnoses Are Common in Pyruvate Kinase Deficient Patients with Single or No Pklr Coding Mutations. Blood 2018, 132: 3607. DOI: 10.1182/blood-2018-99-117805.Peer-Reviewed Original ResearchWhole-genome sequencingPyruvate kinase-deficient patientsSplice siteDonor splice sitePyruvate kinasePK-deficient patientsGenome sequencingPKLR geneSequence analysisWhole-exome sequencingIntron mutationsDominant negative phenotypeExon 7Exon 10Detailed sequence analysisPyruvate kinase geneDisease-associated variantsRare genetic variantsNormal mRNA processingSplice acceptor siteRegion mutationsIntron retentionErythroid promoterGenome databasePremature chain termination
2014
Assessment of HbF QTLs Affecting Disease Severity and Genetic Analysis in Patients Homozygous for Codon 8 (–AA) β0-Thalassemia Mutation
Jiang Z, Huang S, Luo H, Akar N, Basak A, Al-Allawi N, Unal S, Gumruk F, Davis L, Morrison T, Campbell A, Gallagher P, Forget B, Steinberg M, Chui D. Assessment of HbF QTLs Affecting Disease Severity and Genetic Analysis in Patients Homozygous for Codon 8 (–AA) β0-Thalassemia Mutation. Blood 2014, 124: 2690. DOI: 10.1182/blood.v124.21.2690.2690.Peer-Reviewed Original ResearchQuantitative trait lociGene clusterIntergenic regionHbF quantitative trait lociΓ-globin gene expressionKb intergenic regionSevere phenotypeMild phenotypeHBS1L-MYB intergenic regionΒ-globin gene clusterGenome-wide SNP arraysMild disease phenotypeDisease phenotypeMinor alleleWhole-genome sequencingTrait lociHPFH mutationNovel SNPsGenetic analysisSNP arrayGene expressionΒ-hemoglobinopathiesGenome sequencingQTL genotypesWhole-exome sequencing