Screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease
Early-onset Alzheimer’s disease (EOAD) can be familial (FAD) or sporadic (sEOAD); both have a disease onset ≤ 65 years of age. 451 sEOAD samples were screened for known causative mutations in exon 16 and 17 of the Amyloid Precursor Protein gene (APP). Four samples were shown to be heterozygous for...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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Elsevier
2016
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| Online Access: | https://eprints.nottingham.ac.uk/46889/ |
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| author | Barber, Imelda S. García-Cárdenas, Jennyfer M. Sakdapanichkul, Chidchanok Deacon, Christopher Zapata Erazo, Gabriela Guerreiro, Rita Bras, Jose Hernandez, Dena Singleton, Andrew Guetta-Baranes, Tamar Braae, Anne Clement, Naomi Patel, Tulsi Brookes, Keeley Medway, Christopher Chappell, Sally Mann, David M. Morgan, Kevin |
| author_facet | Barber, Imelda S. García-Cárdenas, Jennyfer M. Sakdapanichkul, Chidchanok Deacon, Christopher Zapata Erazo, Gabriela Guerreiro, Rita Bras, Jose Hernandez, Dena Singleton, Andrew Guetta-Baranes, Tamar Braae, Anne Clement, Naomi Patel, Tulsi Brookes, Keeley Medway, Christopher Chappell, Sally Mann, David M. Morgan, Kevin |
| author_sort | Barber, Imelda S. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Early-onset Alzheimer’s disease (EOAD) can be familial (FAD) or sporadic (sEOAD); both have a disease onset ≤ 65 years of age. 451 sEOAD samples were screened for known causative mutations in exon 16 and 17 of the Amyloid Precursor Protein gene (APP). Four samples were shown to be heterozygous for one of three known causative mutations: p.A713T, p.V717I and p.V717G, this highlights the importance of screening EOAD patients for causative mutations. Additionally, we document an intronic 6 base pair (bp) deletion located 83 bp downstream of exon 17 (rs367709245, IVS17 83-88delAAGTAT), which has a non-significantly increased minor allele frequency in our sEOAD cohort (0.006) compared to LOAD (0.002) and controls (0.002). To assess the effect of the 6 bp deletion on splicing, COS-7 and BE (2)-C cells were transfected with a minigene vector encompassing exon 17. There was no change in splicing of exon 17 from constructs containing either wild type or deletion inserts. Sequencing of cDNA generated from cerebellum and temporal cortex of a patient harbouring the deletion found no evidence of transcripts with exon 17 removed. |
| first_indexed | 2025-11-14T20:03:35Z |
| format | Article |
| id | nottingham-46889 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:03:35Z |
| publishDate | 2016 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-468892020-05-04T17:34:05Z https://eprints.nottingham.ac.uk/46889/ Screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease Barber, Imelda S. García-Cárdenas, Jennyfer M. Sakdapanichkul, Chidchanok Deacon, Christopher Zapata Erazo, Gabriela Guerreiro, Rita Bras, Jose Hernandez, Dena Singleton, Andrew Guetta-Baranes, Tamar Braae, Anne Clement, Naomi Patel, Tulsi Brookes, Keeley Medway, Christopher Chappell, Sally Mann, David M. Morgan, Kevin Early-onset Alzheimer’s disease (EOAD) can be familial (FAD) or sporadic (sEOAD); both have a disease onset ≤ 65 years of age. 451 sEOAD samples were screened for known causative mutations in exon 16 and 17 of the Amyloid Precursor Protein gene (APP). Four samples were shown to be heterozygous for one of three known causative mutations: p.A713T, p.V717I and p.V717G, this highlights the importance of screening EOAD patients for causative mutations. Additionally, we document an intronic 6 base pair (bp) deletion located 83 bp downstream of exon 17 (rs367709245, IVS17 83-88delAAGTAT), which has a non-significantly increased minor allele frequency in our sEOAD cohort (0.006) compared to LOAD (0.002) and controls (0.002). To assess the effect of the 6 bp deletion on splicing, COS-7 and BE (2)-C cells were transfected with a minigene vector encompassing exon 17. There was no change in splicing of exon 17 from constructs containing either wild type or deletion inserts. Sequencing of cDNA generated from cerebellum and temporal cortex of a patient harbouring the deletion found no evidence of transcripts with exon 17 removed. Elsevier 2016-03-01 Article PeerReviewed Barber, Imelda S., García-Cárdenas, Jennyfer M., Sakdapanichkul, Chidchanok, Deacon, Christopher, Zapata Erazo, Gabriela, Guerreiro, Rita, Bras, Jose, Hernandez, Dena, Singleton, Andrew, Guetta-Baranes, Tamar, Braae, Anne, Clement, Naomi, Patel, Tulsi, Brookes, Keeley, Medway, Christopher, Chappell, Sally, Mann, David M. and Morgan, Kevin (2016) Screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease. Neurobiology of Aging, 39 . 220.e1-220.e7. ISSN 1558-1497 Alzheimer's disease ; Early-onset ; Sporadic ; Screening ; APP ; rs367709245 http://www.sciencedirect.com/science/article/pii/S0197458015006156?via%3Dihub doi:10.1016/j.neurobiolaging.2015.12.011 doi:10.1016/j.neurobiolaging.2015.12.011 |
| spellingShingle | Alzheimer's disease ; Early-onset ; Sporadic ; Screening ; APP ; rs367709245 Barber, Imelda S. García-Cárdenas, Jennyfer M. Sakdapanichkul, Chidchanok Deacon, Christopher Zapata Erazo, Gabriela Guerreiro, Rita Bras, Jose Hernandez, Dena Singleton, Andrew Guetta-Baranes, Tamar Braae, Anne Clement, Naomi Patel, Tulsi Brookes, Keeley Medway, Christopher Chappell, Sally Mann, David M. Morgan, Kevin Screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease |
| title | Screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease |
| title_full | Screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease |
| title_fullStr | Screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease |
| title_full_unstemmed | Screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease |
| title_short | Screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease |
| title_sort | screening exon 16 and 17 of the amyloid precursor protein gene in sporadic early-onset alzheimer's disease |
| topic | Alzheimer's disease ; Early-onset ; Sporadic ; Screening ; APP ; rs367709245 |
| url | https://eprints.nottingham.ac.uk/46889/ https://eprints.nottingham.ac.uk/46889/ https://eprints.nottingham.ac.uk/46889/ |