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Amyloid Precursor Protein A713T Mutation in Calabrian Patients with Alzheimer’s Disease: A Population Genomics Approach to Estimate Inheritance from a Common Ancestor

Mutation A713T in the amyloid precursor protein (APP) has been linked to cases of Alzheimer’s disease (AD), cerebral amyloid angiopathy (CAA) and cerebrovascular disease. Despite its rarity, it has been observed in several families from the same geographical area, in the Calabria region in Southern...

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Autores principales: Abondio, Paolo, Sarno, Stefania, Giuliani, Cristina, Laganà, Valentina, Maletta, Raffaele, Bernardi, Livia, Bruno, Francesco, Colao, Rosanna, Puccio, Gianfranco, Frangipane, Francesca, Borroni, Barbara, Van Broeckhoven, Christine, Luiselli, Donata, Bruni, Amalia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773445/
https://www.ncbi.nlm.nih.gov/pubmed/35052700
http://dx.doi.org/10.3390/biomedicines10010020
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author Abondio, Paolo
Sarno, Stefania
Giuliani, Cristina
Laganà, Valentina
Maletta, Raffaele
Bernardi, Livia
Bruno, Francesco
Colao, Rosanna
Puccio, Gianfranco
Frangipane, Francesca
Borroni, Barbara
Van Broeckhoven, Christine
Luiselli, Donata
Bruni, Amalia
author_facet Abondio, Paolo
Sarno, Stefania
Giuliani, Cristina
Laganà, Valentina
Maletta, Raffaele
Bernardi, Livia
Bruno, Francesco
Colao, Rosanna
Puccio, Gianfranco
Frangipane, Francesca
Borroni, Barbara
Van Broeckhoven, Christine
Luiselli, Donata
Bruni, Amalia
author_sort Abondio, Paolo
collection PubMed
description Mutation A713T in the amyloid precursor protein (APP) has been linked to cases of Alzheimer’s disease (AD), cerebral amyloid angiopathy (CAA) and cerebrovascular disease. Despite its rarity, it has been observed in several families from the same geographical area, in the Calabria region in Southern Italy. Genotyping of 720,000 genome-wide SNPs with the HumanOmniExpress BeadChip was performed for six patients that were representative of apparently unrelated Calabrian families, as well as a Belgian subject of Italian descent (all with the same A713T mutation and disease). Their genomic structure and genetic relationships were analyzed. Demographic reconstruction and coalescent theory were applied to estimate the time of the most recent common ancestor (tMRCA) among patients. Results show that all A713T carriers fell into the genetic variability of Southern Italy and were not more closely related to each other than to any other healthy Calabrian individual. However, five out of seven patients shared a 1.7 Mbp-long DNA segment centered on the A713T mutation, making it possible to estimate a tMRCA for its common origin in the Calabrian region dating back over 1000 years. The analysis of affected individuals with methodologies based on human population genomics thus provides informative insights in support of clinical observations and biomedical research.
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spelling pubmed-87734452022-01-21 Amyloid Precursor Protein A713T Mutation in Calabrian Patients with Alzheimer’s Disease: A Population Genomics Approach to Estimate Inheritance from a Common Ancestor Abondio, Paolo Sarno, Stefania Giuliani, Cristina Laganà, Valentina Maletta, Raffaele Bernardi, Livia Bruno, Francesco Colao, Rosanna Puccio, Gianfranco Frangipane, Francesca Borroni, Barbara Van Broeckhoven, Christine Luiselli, Donata Bruni, Amalia Biomedicines Article Mutation A713T in the amyloid precursor protein (APP) has been linked to cases of Alzheimer’s disease (AD), cerebral amyloid angiopathy (CAA) and cerebrovascular disease. Despite its rarity, it has been observed in several families from the same geographical area, in the Calabria region in Southern Italy. Genotyping of 720,000 genome-wide SNPs with the HumanOmniExpress BeadChip was performed for six patients that were representative of apparently unrelated Calabrian families, as well as a Belgian subject of Italian descent (all with the same A713T mutation and disease). Their genomic structure and genetic relationships were analyzed. Demographic reconstruction and coalescent theory were applied to estimate the time of the most recent common ancestor (tMRCA) among patients. Results show that all A713T carriers fell into the genetic variability of Southern Italy and were not more closely related to each other than to any other healthy Calabrian individual. However, five out of seven patients shared a 1.7 Mbp-long DNA segment centered on the A713T mutation, making it possible to estimate a tMRCA for its common origin in the Calabrian region dating back over 1000 years. The analysis of affected individuals with methodologies based on human population genomics thus provides informative insights in support of clinical observations and biomedical research. MDPI 2021-12-23 /pmc/articles/PMC8773445/ /pubmed/35052700 http://dx.doi.org/10.3390/biomedicines10010020 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Abondio, Paolo
Sarno, Stefania
Giuliani, Cristina
Laganà, Valentina
Maletta, Raffaele
Bernardi, Livia
Bruno, Francesco
Colao, Rosanna
Puccio, Gianfranco
Frangipane, Francesca
Borroni, Barbara
Van Broeckhoven, Christine
Luiselli, Donata
Bruni, Amalia
Amyloid Precursor Protein A713T Mutation in Calabrian Patients with Alzheimer’s Disease: A Population Genomics Approach to Estimate Inheritance from a Common Ancestor
title Amyloid Precursor Protein A713T Mutation in Calabrian Patients with Alzheimer’s Disease: A Population Genomics Approach to Estimate Inheritance from a Common Ancestor
title_full Amyloid Precursor Protein A713T Mutation in Calabrian Patients with Alzheimer’s Disease: A Population Genomics Approach to Estimate Inheritance from a Common Ancestor
title_fullStr Amyloid Precursor Protein A713T Mutation in Calabrian Patients with Alzheimer’s Disease: A Population Genomics Approach to Estimate Inheritance from a Common Ancestor
title_full_unstemmed Amyloid Precursor Protein A713T Mutation in Calabrian Patients with Alzheimer’s Disease: A Population Genomics Approach to Estimate Inheritance from a Common Ancestor
title_short Amyloid Precursor Protein A713T Mutation in Calabrian Patients with Alzheimer’s Disease: A Population Genomics Approach to Estimate Inheritance from a Common Ancestor
title_sort amyloid precursor protein a713t mutation in calabrian patients with alzheimer’s disease: a population genomics approach to estimate inheritance from a common ancestor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773445/
https://www.ncbi.nlm.nih.gov/pubmed/35052700
http://dx.doi.org/10.3390/biomedicines10010020
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