Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease

Imelda S. Barber, Jennyfer M. Garc??a-C??rdenas, Chidchanok Sakdapanichkul, Christopher Deacon, Gabriela Zapata Erazo, Rita Guerreiro, Jose Bras, Dena Hernandez, Andrew B Singleton, Tamar Guetta-Baranes, Anne Braae, Naomi Clement, Tulsi Patel, Keeley Brookes, Christopher Medway, Sally Chappell, David M. Mann, Peter Passmore, David Craig, Janet JohnstonBernadette McGuinness, Stephen Todd, Reinhard Heun, Heike Kolsch, Patrick G Kehoe, Emma R L C Vardy, Nigel M Hooper, Stuart Pickering-Brown, Julie Snowden, Anna Richardson, Matt Jones, David Neary, Jenny Harris, James Lowe, A David Smith, Gordon Wilcock, Donald Warden, Clive Holmes, K. Morgan

Research output: Chapter in Book/Report/Conference proceedingChapter

7 Citations (Scopus)

Abstract

Early-onset Alzheimer's disease (EOAD) can be familial (FAD) or sporadic EOAD (sEOAD); both have a disease onset ???65 years of age. A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. Four samples were shown to be heterozygous for 1 of 3 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 nonsignificantly 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 harboring the deletion found no evidence of transcripts with exon 17 removed.
Original languageEnglish
Title of host publicationNeurobiology of Aging
PublisherElsevier Inc.
Pages220.e1-220.e7
ISBN (Print)1558-1497 (Electronic)\r0197-4580 (Linking)
DOIs
Publication statusPublished - 01 Mar 2016

Publication series

NameNeurobiology of Aging
Volume39

Fingerprint

Amyloid beta-Protein Precursor
Exons
Alzheimer Disease
Base Pairing
Genes
Mutation
Flavin-Adenine Dinucleotide
Temporal Lobe
Gene Frequency
Cerebellum
Complementary DNA

Keywords

  • APP
  • Alzheimer's disease
  • Early-onset
  • Rs367709245
  • Screening
  • Sporadic

Cite this

Barber, I. S., Garc??a-C??rdenas, J. M., Sakdapanichkul, C., Deacon, C., Zapata Erazo, G., Guerreiro, R., ... Morgan, K. (2016). Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease. In Neurobiology of Aging (pp. 220.e1-220.e7). (Neurobiology of Aging; Vol. 39). Elsevier Inc.. https://doi.org/10.1016/j.neurobiolaging.2015.12.011
Barber, Imelda S. ; Garc??a-C??rdenas, Jennyfer M. ; Sakdapanichkul, Chidchanok ; Deacon, Christopher ; Zapata Erazo, Gabriela ; Guerreiro, Rita ; Bras, Jose ; Hernandez, Dena ; Singleton, Andrew B ; Guetta-Baranes, Tamar ; Braae, Anne ; Clement, Naomi ; Patel, Tulsi ; Brookes, Keeley ; Medway, Christopher ; Chappell, Sally ; Mann, David M. ; Passmore, Peter ; Craig, David ; Johnston, Janet ; McGuinness, Bernadette ; Todd, Stephen ; Heun, Reinhard ; Kolsch, Heike ; Kehoe, Patrick G ; Vardy, Emma R L C ; Hooper, Nigel M ; Pickering-Brown, Stuart ; Snowden, Julie ; Richardson, Anna ; Jones, Matt ; Neary, David ; Harris, Jenny ; Lowe, James ; Smith, A David ; Wilcock, Gordon ; Warden, Donald ; Holmes, Clive ; Morgan, K. / Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease. Neurobiology of Aging. Elsevier Inc., 2016. pp. 220.e1-220.e7 (Neurobiology of Aging).
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abstract = "Early-onset Alzheimer's disease (EOAD) can be familial (FAD) or sporadic EOAD (sEOAD); both have a disease onset ???65 years of age. A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. Four samples were shown to be heterozygous for 1 of 3 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 nonsignificantly 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 harboring the deletion found no evidence of transcripts with exon 17 removed.",
keywords = "APP, Alzheimer's disease, Early-onset, Rs367709245, Screening, Sporadic",
author = "Barber, {Imelda S.} and Garc??a-C??rdenas, {Jennyfer M.} and Chidchanok Sakdapanichkul and Christopher Deacon and {Zapata Erazo}, Gabriela and Rita Guerreiro and Jose Bras and Dena Hernandez and Singleton, {Andrew B} and Tamar Guetta-Baranes and Anne Braae and Naomi Clement and Tulsi Patel and Keeley Brookes and Christopher Medway and Sally Chappell and Mann, {David M.} and Peter Passmore and David Craig and Janet Johnston and Bernadette McGuinness and Stephen Todd and Reinhard Heun and Heike Kolsch and Kehoe, {Patrick G} and Vardy, {Emma R L C} and Hooper, {Nigel M} and Stuart Pickering-Brown and Julie Snowden and Anna Richardson and Matt Jones and David Neary and Jenny Harris and James Lowe and Smith, {A David} and Gordon Wilcock and Donald Warden and Clive Holmes and K. Morgan",
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Barber, IS, Garc??a-C??rdenas, JM, Sakdapanichkul, C, Deacon, C, Zapata Erazo, G, Guerreiro, R, Bras, J, Hernandez, D, Singleton, AB, Guetta-Baranes, T, Braae, A, Clement, N, Patel, T, Brookes, K, Medway, C, Chappell, S, Mann, DM, Passmore, P, Craig, D, Johnston, J, McGuinness, B, Todd, S, Heun, R, Kolsch, H, Kehoe, PG, Vardy, ERLC, Hooper, NM, Pickering-Brown, S, Snowden, J, Richardson, A, Jones, M, Neary, D, Harris, J, Lowe, J, Smith, AD, Wilcock, G, Warden, D, Holmes, C & Morgan, K 2016, Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease. in Neurobiology of Aging. Neurobiology of Aging, vol. 39, Elsevier Inc., pp. 220.e1-220.e7. https://doi.org/10.1016/j.neurobiolaging.2015.12.011

Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease. / Barber, Imelda S.; Garc??a-C??rdenas, Jennyfer M.; Sakdapanichkul, Chidchanok; Deacon, Christopher; Zapata Erazo, Gabriela; Guerreiro, Rita; Bras, Jose; Hernandez, Dena; Singleton, Andrew B; Guetta-Baranes, Tamar; Braae, Anne; Clement, Naomi; Patel, Tulsi; Brookes, Keeley; Medway, Christopher; Chappell, Sally; Mann, David M.; Passmore, Peter; Craig, David; Johnston, Janet; McGuinness, Bernadette; Todd, Stephen; Heun, Reinhard; Kolsch, Heike; Kehoe, Patrick G; Vardy, Emma R L C; Hooper, Nigel M; Pickering-Brown, Stuart; Snowden, Julie; Richardson, Anna; Jones, Matt; Neary, David; Harris, Jenny; Lowe, James; Smith, A David; Wilcock, Gordon; Warden, Donald; Holmes, Clive; Morgan, K.

Neurobiology of Aging. Elsevier Inc., 2016. p. 220.e1-220.e7 (Neurobiology of Aging; Vol. 39).

Research output: Chapter in Book/Report/Conference proceedingChapter

TY - CHAP

T1 - Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease

AU - Barber, Imelda S.

AU - Garc??a-C??rdenas, Jennyfer M.

AU - Sakdapanichkul, Chidchanok

AU - Deacon, Christopher

AU - Zapata Erazo, Gabriela

AU - Guerreiro, Rita

AU - Bras, Jose

AU - Hernandez, Dena

AU - Singleton, Andrew B

AU - Guetta-Baranes, Tamar

AU - Braae, Anne

AU - Clement, Naomi

AU - Patel, Tulsi

AU - Brookes, Keeley

AU - Medway, Christopher

AU - Chappell, Sally

AU - Mann, David M.

AU - Passmore, Peter

AU - Craig, David

AU - Johnston, Janet

AU - McGuinness, Bernadette

AU - Todd, Stephen

AU - Heun, Reinhard

AU - Kolsch, Heike

AU - Kehoe, Patrick G

AU - Vardy, Emma R L C

AU - Hooper, Nigel M

AU - Pickering-Brown, Stuart

AU - Snowden, Julie

AU - Richardson, Anna

AU - Jones, Matt

AU - Neary, David

AU - Harris, Jenny

AU - Lowe, James

AU - Smith, A David

AU - Wilcock, Gordon

AU - Warden, Donald

AU - Holmes, Clive

AU - Morgan, K.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Early-onset Alzheimer's disease (EOAD) can be familial (FAD) or sporadic EOAD (sEOAD); both have a disease onset ???65 years of age. A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. Four samples were shown to be heterozygous for 1 of 3 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 nonsignificantly 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 harboring the deletion found no evidence of transcripts with exon 17 removed.

AB - Early-onset Alzheimer's disease (EOAD) can be familial (FAD) or sporadic EOAD (sEOAD); both have a disease onset ???65 years of age. A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. Four samples were shown to be heterozygous for 1 of 3 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 nonsignificantly 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 harboring the deletion found no evidence of transcripts with exon 17 removed.

KW - APP

KW - Alzheimer's disease

KW - Early-onset

KW - Rs367709245

KW - Screening

KW - Sporadic

U2 - 10.1016/j.neurobiolaging.2015.12.011

DO - 10.1016/j.neurobiolaging.2015.12.011

M3 - Chapter

C2 - 26803359

SN - 1558-1497 (Electronic)\r0197-4580 (Linking)

T3 - Neurobiology of Aging

SP - 220.e1-220.e7

BT - Neurobiology of Aging

PB - Elsevier Inc.

ER -

Barber IS, Garc??a-C??rdenas JM, Sakdapanichkul C, Deacon C, Zapata Erazo G, Guerreiro R et al. Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease. In Neurobiology of Aging. Elsevier Inc. 2016. p. 220.e1-220.e7. (Neurobiology of Aging). https://doi.org/10.1016/j.neurobiolaging.2015.12.011