| Title: |
Transcript analysis using long‐read sequencing reveals the complex splicing profile of AD‐associated gene ABCA7 ; Genetics: Genetics and omics of AD I |
| Authors: |
Duchateau, Lena; Küçükali, Fahri; Van Dongen, Jasper; Bossaerts, Liene; Hens, Elisabeth; De Roeck, Arne; Mateiu, Ligia; Van Broeckhoven, Christine; Sleegers, Kristel |
| Source: |
Alzheimer's & Dementia ; volume 16, issue S3 ; ISSN 1552-5260 1552-5279 |
| Publisher Information: |
Wiley |
| Publication Year: |
2020 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background The ATP‐Binding Cassette Subfamily A member 7 ( ABCA7 ) gene is one of most alluring risk genes for Alzheimer’s disease (AD). Of special interest are alternative splice events that are a) able to rescue the effect of premature termination codon (PTC) mutations, possibly explaining the wide range in phenotype and onset age of PTC mutation carriers, and b) associated with an elongated intronic variable number of tandem repeat (VNTR). However, our knowledge of alternative splice events in ABCA7 is limited. Here, we analyze the ABCA7 transcript using long‐read sequencing in a unique population of ABCA7 PTC carriers. Moreover, we look for possible association between rescue splicing and AD onset age. Methods We characterized the ABCA7 transcript of 28 AD patients (24 PTC carriers), 17 controls (11 PTC carriers) and 5 mild cognitive impairment patients using targeted long‐read cDNA sequencing on an Oxford Nanopore MinION platform. RNA was extracted from 47 lymphoblastoid cell lines, as well as 4 hippocampi and 2 prefrontal cortices. Alternative splice events and rescue events were quantified using the full‐length alternative isoform analysis of RNA (FLAIR) pipeline and an in‐house R script. Result All PTC mutation carriers displayed nonsense‐mediated mRNA degradation escape (mutant reads |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/alz.042815 |
| Availability: |
https://doi.org/10.1002/alz.042815; https://onlinelibrary.wiley.com/doi/pdf/10.1002/alz.042815 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.D9BC5390 |
| Database: |
BASE |