| Title |
An intronic VNTR affects splicing of ABCA7 and increases risk of Alzheimer’s disease
|
|---|---|
| Published in |
Acta Neuropathologica, March 2018
|
| DOI | 10.1007/s00401-018-1841-z |
| Pubmed ID | |
| Authors |
Arne De Roeck, Lena Duchateau, Jasper Van Dongen, Rita Cacace, Maria Bjerke, Tobi Van den Bossche, Patrick Cras, Rik Vandenberghe, Peter P. De Deyn, Sebastiaan Engelborghs, Christine Van Broeckhoven, Kristel Sleegers, On Behalf of the BELNEU Consortium |
| Abstract |
Mutations leading to premature termination codons in ATP-Binding Cassette Subfamily A Member 7 (ABCA7) are high penetrant risk factors of Alzheimer's disease (AD). The influence of other genetic variants in ABCA7 and downstream functional mechanisms, however, is poorly understood. To address this knowledge gap, we investigated tandem repetitive regions in ABCA7 in a Belgian cohort of 1529 AD patients and control individuals and identified an intronic variable number tandem repeat (VNTR). We observed strong association between VNTR length and a genome-wide associated signal for AD in the ABCA7 locus. Expanded VNTR alleles were highly enriched in AD patients [odds ratio = 4.5 (1.3-24.2)], and VNTR length inversely correlated with amyloid β1-42in cerebrospinal fluid and ABCA7 expression. In addition, we identified three novel ABCA7 alternative splicing events. One isoform in particular-which is formed through exon 19 skipping-lacks the first nucleotide binding domain of ABCA7 and is abundant in brain tissue. We observed a tight correlation between exon 19 skipping and VNTR length. Our findings underline the importance of studying repetitive DNA in complex disorders and expand the contribution of genetic and transcript variation in ABCA7 to AD. |
X Demographics
The data shown below were collected from the profiles of 9 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 4 | 44% |
| Spain | 1 | 11% |
| United Kingdom | 1 | 11% |
| Unknown | 3 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 44% |
| Scientists | 3 | 33% |
| Practitioners (doctors, other healthcare professionals) | 1 | 11% |
| Science communicators (journalists, bloggers, editors) | 1 | 11% |
Mendeley readers
The data shown below were compiled from readership statistics for 114 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 114 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 21 | 18% |
| Student > Ph. D. Student | 16 | 14% |
| Student > Bachelor | 13 | 11% |
| Student > Master | 11 | 10% |
| Professor | 10 | 9% |
| Other | 14 | 12% |
| Unknown | 29 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 27 | 24% |
| Agricultural and Biological Sciences | 18 | 16% |
| Neuroscience | 17 | 15% |
| Medicine and Dentistry | 10 | 9% |
| Computer Science | 3 | 3% |
| Other | 9 | 8% |
| Unknown | 30 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 18. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 July 2023.
All research outputs
#1,893,100
of 24,282,284 outputs
Outputs from Acta Neuropathologica
#417
of 2,470 outputs
Outputs of similar age
#41,219
of 333,495 outputs
Outputs of similar age from Acta Neuropathologica
#14
of 44 outputs
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