Matches in SemOpenAlex for { <https://semopenalex.org/work/W4210334516> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W4210334516 abstract "Initially, ABCA7 was associated with Alzheimer's disease (AD) in large genome-wide association studies. Targeted resequencing of ABCA7 suggested a role for rare premature termination codon (PTC) mutations. We observed loss of ABCA7 in PTC carriers, although with high variability due to differences in transcript rescue. Additionally, rare missense mutations are present in ABCA7 with unknown effect on the protein. We aimed to investigate the contribution of rare (MAF≤1%) mutations or compound heterozygous mutations in ABCA7 in Belgian AD patient and control cohorts, as well as the effect of rare missense mutations on the subcellular localization of the protein.Targeted resequencing or whole exome sequencing of ABCA7 exons and splice sites in 1375 Belgian AD patients and 976 controls. We validated all rare, non-synonymous coding and splice mutations. Allele-specific PCR, haplotype sharing analysis and long-read sequencing to determine cis/trans configuration of compound heterozygous mutations. In vitro mutagenesis to introduce missense mutations of interest in an entry vector. Gateway cloning to generate wild type and mutant ABCA7 pCR3 expression vectors with a C-terminal EmGFP-tag. Transfection of HeLa and HEK293 cells for immunofluorescence microscopy to localize wild type versus mutant ABCA7.We identified rare mutations in 12.7% (175/1375) of the patients and in 7.8% (76/976) of the controls. We observed co-segregation of p.G1820S with AD in a family with apparent autosomal dominant inheritance. We observed compound heterozygous mutations in 10 patients (0.73%) and five controls (0.51%). We confirmed trans configuration in four of the patients and cis configuration in four other patients. In the remaining two patients, configuration remains unknown. In the five controls, we confirmed trans configuration in one and cis configuration in the other four. We selected eight missense mutations present in Belgian AD patients (Figure) to introduce in an entry vector. Mutant and wild type entry clones were subcloned in the expression vector to transfect and generate immunofluorescence localization data.We observed an enrichment in patients of rare single mutations and compound heterozygous mutations. In addition, trans compound heterozygous mutations might modify penetrance and pathogenicity. Functional studies of missense mutations are necessary to determine their potential pathogenic effect." @default.
- W4210334516 created "2022-02-08" @default.
- W4210334516 creator A5013074656 @default.
- W4210334516 creator A5013163624 @default.
- W4210334516 creator A5015001209 @default.
- W4210334516 creator A5027033208 @default.
- W4210334516 creator A5039638206 @default.
- W4210334516 creator A5041038663 @default.
- W4210334516 creator A5046266581 @default.
- W4210334516 creator A5059991915 @default.
- W4210334516 creator A5071341444 @default.
- W4210334516 creator A9999999999 @default.
- W4210334516 date "2021-12-01" @default.
- W4210334516 modified "2023-10-18" @default.
- W4210334516 title "Rare missense mutations and compound heterozygous mutations in <i>ABCA7</i> contribute to Alzheimer's disease in Belgian patients" @default.
- W4210334516 doi "https://doi.org/10.1002/alz.051341" @default.
- W4210334516 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35108979" @default.
- W4210334516 hasPublicationYear "2021" @default.
- W4210334516 type Work @default.
- W4210334516 citedByCount "0" @default.
- W4210334516 crossrefType "journal-article" @default.
- W4210334516 hasAuthorship W4210334516A5013074656 @default.
- W4210334516 hasAuthorship W4210334516A5013163624 @default.
- W4210334516 hasAuthorship W4210334516A5015001209 @default.
- W4210334516 hasAuthorship W4210334516A5027033208 @default.
- W4210334516 hasAuthorship W4210334516A5039638206 @default.
- W4210334516 hasAuthorship W4210334516A5041038663 @default.
- W4210334516 hasAuthorship W4210334516A5046266581 @default.
- W4210334516 hasAuthorship W4210334516A5059991915 @default.
- W4210334516 hasAuthorship W4210334516A5071341444 @default.
- W4210334516 hasAuthorship W4210334516A9999999999 @default.
- W4210334516 hasBestOaLocation W42103345162 @default.
- W4210334516 hasConcept C104317684 @default.
- W4210334516 hasConcept C12125453 @default.
- W4210334516 hasConcept C153911025 @default.
- W4210334516 hasConcept C180754005 @default.
- W4210334516 hasConcept C36823959 @default.
- W4210334516 hasConcept C501734568 @default.
- W4210334516 hasConcept C54355233 @default.
- W4210334516 hasConcept C75563809 @default.
- W4210334516 hasConcept C86803240 @default.
- W4210334516 hasConceptScore W4210334516C104317684 @default.
- W4210334516 hasConceptScore W4210334516C12125453 @default.
- W4210334516 hasConceptScore W4210334516C153911025 @default.
- W4210334516 hasConceptScore W4210334516C180754005 @default.
- W4210334516 hasConceptScore W4210334516C36823959 @default.
- W4210334516 hasConceptScore W4210334516C501734568 @default.
- W4210334516 hasConceptScore W4210334516C54355233 @default.
- W4210334516 hasConceptScore W4210334516C75563809 @default.
- W4210334516 hasConceptScore W4210334516C86803240 @default.
- W4210334516 hasIssue "S3" @default.
- W4210334516 hasLocation W42103345161 @default.
- W4210334516 hasLocation W42103345162 @default.
- W4210334516 hasLocation W42103345163 @default.
- W4210334516 hasOpenAccess W4210334516 @default.
- W4210334516 hasPrimaryLocation W42103345161 @default.
- W4210334516 hasRelatedWork W1533351568 @default.
- W4210334516 hasRelatedWork W1991651726 @default.
- W4210334516 hasRelatedWork W2329070144 @default.
- W4210334516 hasRelatedWork W2349400098 @default.
- W4210334516 hasRelatedWork W2768077825 @default.
- W4210334516 hasRelatedWork W3155541108 @default.
- W4210334516 hasRelatedWork W3189132110 @default.
- W4210334516 hasRelatedWork W3201076994 @default.
- W4210334516 hasRelatedWork W4287398924 @default.
- W4210334516 hasRelatedWork W2268430446 @default.
- W4210334516 hasVolume "17" @default.
- W4210334516 isParatext "false" @default.
- W4210334516 isRetracted "false" @default.
- W4210334516 workType "article" @default.