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Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications For the Study of Neurodegeneration
Abondio, P.; Bruno, F.; Bruni, A.C.; Luiselli, D. Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration. Int. J. Mol. Sci.2022, 23, 15871.
Abondio, P.; Bruno, F.; Bruni, A.C.; Luiselli, D. Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration. Int. J. Mol. Sci. 2022, 23, 15871.
Abondio, P.; Bruno, F.; Bruni, A.C.; Luiselli, D. Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration. Int. J. Mol. Sci.2022, 23, 15871.
Abondio, P.; Bruno, F.; Bruni, A.C.; Luiselli, D. Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration. Int. J. Mol. Sci. 2022, 23, 15871.
Abstract
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. The present study aims at scanning 70 single-point mutations on the APP gene in a publicly available genetic dataset including 2.504 healthy individuals from 26 populations, and analyzing their distribution. Moreover, 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 have been detected in the worldwide dataset, with several of them being specific for a single individual, population or macroarea. Patterns of segment sharing reflect 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 dementias.
Biology and Life Sciences, Biochemistry and Molecular Biology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
