Search results for "ML"

showing 10 items of 1465 documents

Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder

2017

AbstractGenetic risk factors for autism spectrum disorder (ASD) have yet to be fully elucidated. Postzygotic mosaic mutations (PMMs) have been implicated in several neurodevelopmental disorders and overgrowth syndromes. We systematically evaluated PMMs by leveraging whole-exome sequencing data on a large family-based ASD cohort, the Simons Simplex Collection. We found evidence that 11% of published single nucleotide variant (SNV)de novomutations are potentially PMMs. We then developed a robust SNV PMM calling approach that leverages complementary callers, logistic regression modeling, and additional heuristics. Using this approach, we recalled SNVs and found that 22% ofde novomutations like…

Male0301 basic medicineProbandZygoteautism spectrum disorderSYNGAP1Biologypostzygoticmedicine.disease_causeArticleGermlineCohort Studies03 medical and health sciencessplicing0302 clinical medicineNeurodevelopmental disorderGermline mutationDatabases GeneticGeneticsmedicineHumansMissense mutationGenetic Predisposition to DiseaseChild[ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human geneticsGenetics (clinical)030304 developmental biologyGenetics0303 health sciencesMutationneurodevelopmentsomaticGenetic VariationExonsmedicine.disease030104 developmental biologymosaicism[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human geneticsAutism spectrum disorderCHD2AutismFemalemutation030217 neurology & neurosurgeryexome
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Dopamine and serotonin transporter genotypes moderate sensitivity to maternal expressed emotion: the case of conduct and emotional problems in attent…

2009

Contains fulltext : 80906.pdf (Publisher’s version ) (Closed access) BACKGROUND: Mothers' positive emotions expressed about their children with attention deficit/hyperactivity disorder (ADHD) are associated with a reduced likelihood of comorbid conduct problems (CP). We examined whether this association with CP, and one with emotional problems (EMO), is moderated by variants within three genes, previously reported to be associated with ADHD and to moderate the impact of environmental risks on conduct and/or emotional problems; the dopamine transporter gene (SLC6A3/DAT1), the dopamine D4 receptor gene (DRD4) and the serotonin transporter gene (SLC6A4/5HTT). METHODS: Seven hundred and twenty-…

Male110 012 Social cognition of verbal communicationGenetics and epigenetic pathways of disease [NCMLS 6]MedizinDopamine transportDevelopmental psychology2738 Psychiatry and Mental Health0302 clinical medicineDevelopmental and Educational PsychologyPerception and Action [DCN 1]Emotional expressionGene–environment interactionChildSerotonin transporterSerotonin Plasma Membrane Transport Proteinsbiology05 social sciences10058 Department of Child and Adolescent PsychiatryMother-Child Relations3. Good healthPsychiatry and Mental healthExpressed EmotionConduct disorderChild Preschool/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingFemalePsychologyFunctional Neurogenomics [DCN 2]050104 developmental & child psychologyAdolescentGenotype610 Medicine & healthChild Behavior DisordersMental health [NCEBP 9]150 000 MR Techniques in Brain FunctionGenomic disorders and inherited multi-system disorders [IGMD 3]03 medical and health sciencesSDG 3 - Good Health and Well-beingmental disordersmedicineAttention deficit hyperactivity disorderExpressed emotionHumans0501 psychology and cognitive sciences2735 Pediatrics Perinatology and Child Healthddc:610Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie Psychosomatik und Psychotherapie des Kindes- und JugendaltersDopamine transporter3204 Developmental and Educational PsychologyDopamine Plasma Membrane Transport ProteinsReceptors Dopamine D4medicine.diseaseAttention Deficit Disorder with HyperactivityPediatrics Perinatology and Child Healthbiology.protein030217 neurology & neurosurgery
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Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemother…

2011

Background Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. Design and Methods We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent trials of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) and Hemato-Oncologie voor Volwassenen Nederland (HOVON) groups between 1996 and 2005. Results FLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%) and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (9%) pa…

MaleAIDA PROTOCOLGene mutationmedicine.disease_causeGastroenterologyLeukemia Promyelocytic AcuteRESIDUAL DISEASEhemic and lymphatic diseasesMOLECULAR SUBTYPESChildanthracyclinesMutationRemission InductionFLT3 mutationshemic and immune systemsHematologyMiddle AgedPrognosisall-trans retinoic acidLeukemiaTreatment Outcomeembryonic structuresFemaleTandem exon duplicationmedicine.drugAcute promyelocytic leukemiaAdultmedicine.medical_specialtyAdolescentAntineoplastic AgentsTretinoinACUTE MYELOID-LEUKEMIABiologyYoung AdultQUALITY-CONTROLTretinoinPOOR-PROGNOSISInternal medicinemedicineCoagulopathyHumansAgedprognostic factorsOriginal Articlesacute promyelocytic leukemiamedicine.diseaseSurvival AnalysisINTERNAL TANDEM DUPLICATIONRISK-ADAPTED TREATMENTPML/RAR-ALPHAfms-Like Tyrosine Kinase 3Fms-Like Tyrosine Kinase 3ImmunologyPETHEMA GROUPMutation
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Linkage to chromosome 1p36 for attention-deficit/hyperactivity disorder traits in school and home settings.

2008

Contains fulltext : 69485.pdf (Publisher’s version ) (Closed access) BACKGROUND: Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan specifically designed to map ADHD quantitative trait loci (QTL). METHODS: A set of 1094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative single nucleotide polymorphism (SNP) panel. Two quantitative traits measuring the children's symptoms in home and school settings were collecte…

MaleAdolescentGenetics and epigenetic pathways of disease [NCMLS 6]Genetic LinkageMedizin610 Medicine & healthSingle-nucleotide polymorphismLocus (genetics)Quantitative trait locusNeuroinformatics [DCN 3]Social EnvironmentMental health [NCEBP 9]ArticleWhite PeopleDyslexiaGenomic disorders and inherited multi-system disorders [IGMD 3]03 medical and health sciences0302 clinical medicineCognitive neurosciences [UMCN 3.2]Genetic linkagemental disordersmedicinePerception and Action [DCN 1]HumansAttention deficit hyperactivity disorderddc:610Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie Psychosomatik und Psychotherapie des Kindes- und JugendaltersChildBiological PsychiatryGenetics0303 health sciencesSchools030305 genetics & heredityDyslexia10058 Department of Child and Adolescent PsychiatryHeritabilitymedicine.disease030227 psychiatryPhenotypeGenetic defects of metabolism [UMCN 5.1]Attention Deficit Disorder with HyperactivityChromosomes Human Pair 1Child PreschoolTraitFemalePsychology2803 Biological PsychiatryFunctional Neurogenomics [DCN 2]
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Genome-wide association study identifies novel susceptibility loci for KIT D816V positive mastocytosis

2021

Mastocytosis is a rare myeloid neoplasm characterized by uncontrolled expansion of mast cells, driven in >80% of affected individuals by acquisition of the KIT D816V mutation. To explore the hypothesis that inherited variation predisposes to mastocytosis, we performed a two-stage genome-wide association study, analyzing 1,035 individuals with KIT D816V positive disease and 17,960 healthy control individuals from five European populations. After quality control, we tested 592,007 SNPs at stage 1 and 75 SNPs at stage 2 for association by using logistic regression and performed a fixed effects meta-analysis to combine evidence across the two stages. From the meta-analysis, we identified three …

MaleAmino Acid Transport System y+TERTReceptors Cytoplasmic and NuclearGenome-wide association studySingle-nucleotide polymorphismDiseaseBiologyQuantitative trait locusPolymorphism Single NucleotideGermlineArticleGenetic variationCEBPACEBPAGeneticsHumansTBL1XR1Genetic Predisposition to DiseaseGeneTelomeraseGenetics (clinical)GeneticsInterleukin-13KITIntronsRepressor ProteinsProto-Oncogene Proteins c-kitD816VCebpa ; D816v ; Kit ; Mastocytosis ; Myeloid Cancer ; Tbl1xr1 ; TertCCAAT-Enhancer-Binding ProteinsDNA IntergenicFemaleRNA Long NoncodingTryptasesMyeloid cancerMastocytosisGenome-Wide Association Study
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The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation.

2014

The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared …

MaleCancer ResearchCell Cycle Proteinsmedicine.disease_causeFusion geneCDKN2AMedicine and Health Sciences2.1 Biological and endogenous factorsAetiologyChildGenetics (clinical)CancerPediatricMutationTissue microarrayTumorGenomeSarcomasHigh-Throughput Nucleotide SequencingAntigens NuclearSarcomaNeoplasm ProteinsOncologyChild PreschoolFemaleSarcomaResearch ArticleBiotechnologyHumanAdultPediatric Research Initiativelcsh:QH426-470Cohesin complexAdolescentPediatric CancerEwing SarcomaSarcoma EwingBiologyDisease-Free SurvivalFrameshift mutationCell LineGermline mutationRare DiseasesCell Line TumorEwingCancer GeneticsmedicineGeneticsHumansNuclearGenetic TestingAntigensPreschoolMolecular BiologyEcology Evolution Behavior and SystematicsGenome HumanHuman GenomeBiology and Life SciencesCancers and NeoplasmsInfantmedicine.diseaselcsh:GeneticsOrphan DrugMutationCancer researchGene DeletionDevelopmental Biology
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Somatic mutation profiles as molecular classifiers of ulcerative colitis-associated colorectal cancer.

2021

Ulcerative colitis increases colorectal cancer risk by mechanisms that remain incompletely understood. We approached this question by determining the genetic and epigenetic profiles of colitis-associated colorectal carcinomas (CA-CRC). The findings were compared to Lynch syndrome (LS), a different form of cancer predisposition that shares the importance of immunological factors in tumorigenesis. CA-CRCs (n=27) were investigated for microsatellite instability, CpG island methylator phenotype, and somatic mutations of 999 cancer-relevant genes ("Pan-cancer" panel). A subpanel of "Pan-cancer" design (578 genes) was used for LS colorectal tumors (n=28). Mutational loads and signatures stratifie…

MaleCancer ResearchColorectal cancermedicine.disease_cause0302 clinical medicinesomatic mutationPromoter Regions Genetictulehdukselliset suolistosairaudetMiddle AgedLynch syndrome3. Good healthOncology030220 oncology & carcinogenesissyöpätauditDNA mismatch repairFemaleMicrosatellite InstabilityMutL Protein Homolog 1Adult3122 Cancerscolorectal cancersuolistosyövätBiologymikrosatelliititMLH103 medical and health sciencesGermline mutationmedicineHumansLynchin oireyhtymäulcerative colitisDNA-analyysiCpG Island Methylator PhenotypeMicrosatellite instabilitySequence Analysis DNADNA Methylationmedicine.diseaseColorectal Neoplasms Hereditary NonpolyposisLynch syndromeUlcerative colitisMutationCancer researchmicrosatellite instabilityColitis UlcerativeCpG IslandsmutaatiotColitis-Associated NeoplasmsTumor Suppressor Protein p53CarcinogenesisInternational journal of cancerREFERENCES
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Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease

2017

Abstract In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD‐HCC. In 40 patients with NAFLD‐HCC, 45 with NAFLD‐cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT‐PCR and hTERT coding regions and intron–exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD‐PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequ…

MaleCancer ResearchHepatocellular carcinomaSeverity of Illness IndexGermlineLoss of heterozygosityCohort StudiesLiver disease0302 clinical medicineNon-alcoholic Fatty Liver DiseaseNuclear Medicine and ImagingNonalcoholic fatty liver disease80 and overLeukocytesTelomeraseTelomere ShorteningOriginal ResearchCancer BiologyAged 80 and overHepatocellular carcinoma; Nonalcoholic fatty liver; Rare germline mutations; Telomerase reverse transcriptase; Telomere; Oncology; Radiology Nuclear Medicine and Imaging; Cancer ResearchtelomereLiver Neoplasmstelomerase reverse transcriptaseMiddle Aged3. Good healthPhenotypeOncology030220 oncology & carcinogenesisHepatocellular carcinoma030211 gastroenterology & hepatologyFemaleDisease SusceptibilityRadiologySequence AnalysisRare germline mutationCarcinoma HepatocellularMononuclearBiology03 medical and health sciencesGermline mutationHepatocellular carcinoma; Nonalcoholic fatty liver; Rare germline mutations; Telomerase reverse transcriptase; Telomere; Aged; Aged 80 and over; Alleles; Amino Acid Substitution; Carcinoma Hepatocellular; Cohort Studies; Computational Biology; Disease Susceptibility; Female; Genetic Association Studies; Humans; Leukocytes Mononuclear; Liver Neoplasms; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phenotype; Sequence Analysis DNA; Severity of Illness Index; Telomerase; Telomere; Telomere Shortening; Germ-Line Mutationmedicinenonalcoholic fatty liverHumansRadiology Nuclear Medicine and imagingTelomerase reverse transcriptaseAllelesGenetic Association StudiesGerm-Line MutationAgedrare germline mutationsCarcinomaComputational BiologyHepatocellularDNASequence Analysis DNAmedicine.diseasedigestive system diseasesTelomereAmino Acid SubstitutionCancer researchLeukocytes MononuclearCancer Medicine
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Neuroblastoma after Childhood: Prognostic Relevance of Segmental Chromosome Aberrations, ATRX Protein Status, and Immune Cell Infiltration

2014

AbstractNeuroblastoma (NB) is a common malignancy in children but rarely occurs during adolescence or adulthood. This subgroup is characterized by an indolent disease course, almost uniformly fatal, yet little is known about the biologic characteristics. The aim of this study was to identify differential features regarding DNA copy number alterations, α-thalassemia/mental retardation syndrome X-linked (ATRX) protein expression, and the presence of tumor-associated inflammatory cells. Thirty-one NB patients older than 10 years who were included in the Spanish NB Registry were considered for the current study; seven young and middle-aged adult patients (range 18-60 years) formed part of the c…

MaleCancer ResearchHet heterogeneousGene ExpressionNeuroblastomaImmunophenotypingRegistriesYoung adultNeoplasm MetastasisMLPA multiplex ligation probe amplificationChildIn Situ Hybridization FluorescenceNuclear ProteinsMiddle AgedAYA adolescent and young adultsPrognosislcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogensNCA numerical chromosome aberrationImmunohistochemistryFemaleSCA segmental chromosome aberrationIHC immunohistochemistryNB neuroblastomaAdultX-linked Nuclear ProteinAdolescentaSNP single nucleotide polymorphism arrayBiologyMalignancyChromosome aberrationPolymorphism Single Nucleotidelcsh:RC254-282ArticleImmunophenotypingYoung AdultLymphocytes Tumor-InfiltratingNeuroblastomacnLOH copy-neutral loss of heterozygositymedicineHumansHom homogeneousATRXNeoplasm StagingChromosome AberrationsDNA Helicasesmedicine.diseaseSpainMNNA MYCN not amplifiedCancer researchFSCA focal segmental chromosome aberrationCD8MNA MYCN amplifiedNeoplasia
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POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes

2021

POLE, POLD1, and NTHL1 are involved in DNA replication and have recently been recognized as hereditary cancer-predisposing genes, because their alterations are associated with colorectal cancer and other tumors. POLE/POLD1-associated syndrome shows an autosomal dominant inheritance, whereas NTHL1-associated syndrome follows an autosomal recessive pattern. Although the prevalence of germline monoallelic POLE/POLD1 and biallelic NTHL1 pathogenic variants is low, they determine different phenotypes with a broad tumor spectrum overlapping that of other hereditary conditions like Lynch Syndrome or Familial Adenomatous Polyposis. Endometrial and breast cancers, and probably ovarian and brain tumo…

MaleCancer ResearchSettore MED/06 - Oncologia MedicaColorectal cancerBiologymedicine.disease_causeGermlineFamilial adenomatous polyposisDeoxyribonuclease (Pyrimidine Dimer)Breast cancerNeoplasmsGeneticsmedicineHumansGenetic Predisposition to DiseasePoly-ADP-Ribose Binding ProteinsMolecular BiologyDNA Polymerase IIIGenetic testingMutationPOLD1medicine.diagnostic_testDNA Polymerase IIDNAmedicine.diseaseLynch syndromePOLE POLD1 and NTHL1Lynch SyndromeCancer researchFemaleOncogene
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