Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration
Genetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far ha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15871 |
| _version_ | 1797457282090401792 |
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| author | Paolo Abondio Francesco Bruno Amalia Cecilia Bruni Donata Luiselli |
| author_facet | Paolo Abondio Francesco Bruno Amalia Cecilia Bruni Donata Luiselli |
| author_sort | Paolo Abondio |
| collection | DOAJ |
| description | Genetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. In the present study, 70 single-point mutations on the <i>APP</i> gene in a publicly available genetic dataset that included 2504 healthy individuals from 26 populations were scanned, and their distribution was analyzed. Furthermore, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations were detected in the worldwide dataset, with several of them being specific for a single individual, population, or macroarea. Patterns of segment sharing reflected recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementia. |
| first_indexed | 2024-03-09T16:19:58Z |
| format | Article |
| id | doaj.art-b0caef0e698c4016a4d0aa27ed1862ff |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:19:58Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b0caef0e698c4016a4d0aa27ed1862ff2023-11-24T15:29:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241587110.3390/ijms232415871Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of NeurodegenerationPaolo Abondio0Francesco Bruno1Amalia Cecilia Bruni2Donata Luiselli3Laboratory of Ancient DNA, Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, ItalyRegional Neurogenetic Center (CRN), Department of Primary Care, ASP Catanzaro, 88046 Lamezia Terme, ItalyRegional Neurogenetic Center (CRN), Department of Primary Care, ASP Catanzaro, 88046 Lamezia Terme, ItalyLaboratory of Ancient DNA, Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, ItalyGenetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. In the present study, 70 single-point mutations on the <i>APP</i> gene in a publicly available genetic dataset that included 2504 healthy individuals from 26 populations were scanned, and their distribution was analyzed. Furthermore, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations were detected in the worldwide dataset, with several of them being specific for a single individual, population, or macroarea. Patterns of segment sharing reflected recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementia.https://www.mdpi.com/1422-0067/23/24/15871amyloid precursor proteinAlzheimer’s diseaseneurodegenerative diseasesneurodegenerationdementiapopulation genomics |
| spellingShingle | Paolo Abondio Francesco Bruno Amalia Cecilia Bruni Donata Luiselli Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration International Journal of Molecular Sciences amyloid precursor protein Alzheimer’s disease neurodegenerative diseases neurodegeneration dementia population genomics |
| title | Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration |
| title_full | Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration |
| title_fullStr | Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration |
| title_full_unstemmed | Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration |
| title_short | Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration |
| title_sort | rare amyloid precursor protein point mutations recapitulate worldwide migration and admixture in healthy individuals implications for the study of neurodegeneration |
| topic | amyloid precursor protein Alzheimer’s disease neurodegenerative diseases neurodegeneration dementia population genomics |
| url | https://www.mdpi.com/1422-0067/23/24/15871 |
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