Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease

Michael J Hurley; Claudio Urra; B Maximiliano Garduno; Agostino Bruno; Allison Kimbell; Brent Wilkinson; Cristina Marino-Buslje; Marcelo Ezquer; Fernando Ezquer; Pedro F Aburto; Elie Poulin; Rodrigo A Vasquez; Robert Deacon; Ariel Avila; Francisco Altimiras; Peter Whitney Vanderklish; Guido Zampieri; Claudio Angione; Gabriele Constantino; Todd C Holmes; Marcelo P Coba; Xiangmin Xu; Patricia Cogram

doi:10.3389/fnagi.2022.894994

Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease

Michael J Hurley, Claudio Urra, B Maximiliano Garduno, Agostino Bruno, Allison Kimbell, Brent Wilkinson, Cristina Marino-Buslje, Marcelo Ezquer, Fernando Ezquer, Pedro F Aburto, Elie Poulin, Rodrigo A Vasquez, Robert Deacon, Ariel Avila, Francisco Altimiras, Peter Whitney Vanderklish, Guido Zampieri, Claudio Angione, Gabriele Constantino, Todd C HolmesMarcelo P Coba, Xiangmin Xu, Patricia Cogram

Research output: Contribution to journal › Article › peer-review

Abstract

The degu (Octodon degus) is a diurnal long-lived rodent that can spontaneously develop molecular and behavioral changes that mirror those seen in human aging. With age some degu, but not all individuals, develop cognitive decline and brain pathology like that observed in Alzheimer's disease including neuroinflammation, hyperphosphorylated tau and amyloid plaques, together with other co-morbidities associated with aging such as macular degeneration, cataracts, alterations in circadian rhythm, diabetes and atherosclerosis. Here we report the whole-genome sequencing and analysis of the degu genome, which revealed unique features and molecular adaptations consistent with aging and Alzheimer's disease. We identified single nucleotide polymorphisms in genes associated with Alzheimer's disease including a novel apolipoprotein E (Apoe) gene variant that correlated with an increase in amyloid plaques in brain and modified the in silico predicted degu APOE protein structure and functionality. The reported genome of an unconventional long-lived animal model of aging and Alzheimer's disease offers the opportunity for understanding molecular pathways involved in aging and should help advance biomedical research into treatments for Alzheimer's disease.

Original language	English
Article number	894994
Pages (from-to)	894994
Journal	Frontiers in Aging Neuroscience
Volume	14
Early online date	30 Jun 2022
DOIs	https://doi.org/10.3389/fnagi.2022.894994
Publication status	Published - 30 Jun 2022

Bibliographical note

Funding Information:
We sincerely thank the Fraunhofer Chile Research and all the Biomedicine division team.

Funding Information:
XX and PC were funded by US National Institutes of Health Grant R24AG073198. PC was funded by ANID-FONDECYT 1200928. RV and EP were funded by AFB-170008-CONICYT-Chile-IEB. BW and MC were funded by grant 3R01MH115005-02S1. AA was funded by ANID EX-CONICYT PAI77180086. GZ and CA are grateful for support from Research England's THYME project. TH is funded by R35 GM127102.

Publisher Copyright:
Copyright © 2022 Hurley, Urra, Garduno, Bruno, Kimbell, Wilkinson, Marino-Buslje, Ezquer, Ezquer, Aburto, Poulin, Vasquez, Deacon, Avila, Altimiras, Whitney Vanderklish, Zampieri, Angione, Constantino, Holmes, Coba, Xu and Cogram.

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10.3389/fnagi.2022.894994

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Hurley, M. J., Urra, C., Garduno, B. M., Bruno, A., Kimbell, A., Wilkinson, B., Marino-Buslje, C., Ezquer, M., Ezquer, F., Aburto, P. F., Poulin, E., Vasquez, R. A., Deacon, R., Avila, A., Altimiras, F., Whitney Vanderklish, P., Zampieri, G., Angione, C., Constantino, G., ... Cogram, P. (2022). Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease. Frontiers in Aging Neuroscience, 14, 894994. Article 894994. https://doi.org/10.3389/fnagi.2022.894994

@article{a8ff257df75d46d498df0a850eead47f,

title = "Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease",

abstract = "The degu (Octodon degus) is a diurnal long-lived rodent that can spontaneously develop molecular and behavioral changes that mirror those seen in human aging. With age some degu, but not all individuals, develop cognitive decline and brain pathology like that observed in Alzheimer's disease including neuroinflammation, hyperphosphorylated tau and amyloid plaques, together with other co-morbidities associated with aging such as macular degeneration, cataracts, alterations in circadian rhythm, diabetes and atherosclerosis. Here we report the whole-genome sequencing and analysis of the degu genome, which revealed unique features and molecular adaptations consistent with aging and Alzheimer's disease. We identified single nucleotide polymorphisms in genes associated with Alzheimer's disease including a novel apolipoprotein E (Apoe) gene variant that correlated with an increase in amyloid plaques in brain and modified the in silico predicted degu APOE protein structure and functionality. The reported genome of an unconventional long-lived animal model of aging and Alzheimer's disease offers the opportunity for understanding molecular pathways involved in aging and should help advance biomedical research into treatments for Alzheimer's disease.",

author = "Hurley, {Michael J} and Claudio Urra and Garduno, {B Maximiliano} and Agostino Bruno and Allison Kimbell and Brent Wilkinson and Cristina Marino-Buslje and Marcelo Ezquer and Fernando Ezquer and Aburto, {Pedro F} and Elie Poulin and Vasquez, {Rodrigo A} and Robert Deacon and Ariel Avila and Francisco Altimiras and {Whitney Vanderklish}, Peter and Guido Zampieri and Claudio Angione and Gabriele Constantino and Holmes, {Todd C} and Coba, {Marcelo P} and Xiangmin Xu and Patricia Cogram",

note = "Funding Information: We sincerely thank the Fraunhofer Chile Research and all the Biomedicine division team. Funding Information: XX and PC were funded by US National Institutes of Health Grant R24AG073198. PC was funded by ANID-FONDECYT 1200928. RV and EP were funded by AFB-170008-CONICYT-Chile-IEB. BW and MC were funded by grant 3R01MH115005-02S1. AA was funded by ANID EX-CONICYT PAI77180086. GZ and CA are grateful for support from Research England's THYME project. TH is funded by R35 GM127102. Publisher Copyright: Copyright {\textcopyright} 2022 Hurley, Urra, Garduno, Bruno, Kimbell, Wilkinson, Marino-Buslje, Ezquer, Ezquer, Aburto, Poulin, Vasquez, Deacon, Avila, Altimiras, Whitney Vanderklish, Zampieri, Angione, Constantino, Holmes, Coba, Xu and Cogram.",

year = "2022",

month = jun,

day = "30",

doi = "10.3389/fnagi.2022.894994",

language = "English",

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pages = "894994",

journal = "Frontiers in Aging Neuroscience",

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Hurley, MJ, Urra, C, Garduno, BM, Bruno, A, Kimbell, A, Wilkinson, B, Marino-Buslje, C, Ezquer, M, Ezquer, F, Aburto, PF, Poulin, E, Vasquez, RA, Deacon, R, Avila, A, Altimiras, F, Whitney Vanderklish, P, Zampieri, G, Angione, C, Constantino, G, Holmes, TC, Coba, MP, Xu, X & Cogram, P 2022, 'Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease', Frontiers in Aging Neuroscience, vol. 14, 894994, pp. 894994. https://doi.org/10.3389/fnagi.2022.894994

TY - JOUR

T1 - Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease

AU - Hurley, Michael J

AU - Urra, Claudio

AU - Garduno, B Maximiliano

AU - Bruno, Agostino

AU - Kimbell, Allison

AU - Wilkinson, Brent

AU - Marino-Buslje, Cristina

AU - Ezquer, Marcelo

AU - Ezquer, Fernando

AU - Aburto, Pedro F

AU - Poulin, Elie

AU - Vasquez, Rodrigo A

AU - Deacon, Robert

AU - Avila, Ariel

AU - Altimiras, Francisco

AU - Whitney Vanderklish, Peter

AU - Zampieri, Guido

AU - Angione, Claudio

AU - Constantino, Gabriele

AU - Holmes, Todd C

AU - Coba, Marcelo P

AU - Xu, Xiangmin

AU - Cogram, Patricia

N1 - Funding Information: We sincerely thank the Fraunhofer Chile Research and all the Biomedicine division team. Funding Information: XX and PC were funded by US National Institutes of Health Grant R24AG073198. PC was funded by ANID-FONDECYT 1200928. RV and EP were funded by AFB-170008-CONICYT-Chile-IEB. BW and MC were funded by grant 3R01MH115005-02S1. AA was funded by ANID EX-CONICYT PAI77180086. GZ and CA are grateful for support from Research England's THYME project. TH is funded by R35 GM127102. Publisher Copyright: Copyright © 2022 Hurley, Urra, Garduno, Bruno, Kimbell, Wilkinson, Marino-Buslje, Ezquer, Ezquer, Aburto, Poulin, Vasquez, Deacon, Avila, Altimiras, Whitney Vanderklish, Zampieri, Angione, Constantino, Holmes, Coba, Xu and Cogram.

PY - 2022/6/30

Y1 - 2022/6/30

N2 - The degu (Octodon degus) is a diurnal long-lived rodent that can spontaneously develop molecular and behavioral changes that mirror those seen in human aging. With age some degu, but not all individuals, develop cognitive decline and brain pathology like that observed in Alzheimer's disease including neuroinflammation, hyperphosphorylated tau and amyloid plaques, together with other co-morbidities associated with aging such as macular degeneration, cataracts, alterations in circadian rhythm, diabetes and atherosclerosis. Here we report the whole-genome sequencing and analysis of the degu genome, which revealed unique features and molecular adaptations consistent with aging and Alzheimer's disease. We identified single nucleotide polymorphisms in genes associated with Alzheimer's disease including a novel apolipoprotein E (Apoe) gene variant that correlated with an increase in amyloid plaques in brain and modified the in silico predicted degu APOE protein structure and functionality. The reported genome of an unconventional long-lived animal model of aging and Alzheimer's disease offers the opportunity for understanding molecular pathways involved in aging and should help advance biomedical research into treatments for Alzheimer's disease.

AB - The degu (Octodon degus) is a diurnal long-lived rodent that can spontaneously develop molecular and behavioral changes that mirror those seen in human aging. With age some degu, but not all individuals, develop cognitive decline and brain pathology like that observed in Alzheimer's disease including neuroinflammation, hyperphosphorylated tau and amyloid plaques, together with other co-morbidities associated with aging such as macular degeneration, cataracts, alterations in circadian rhythm, diabetes and atherosclerosis. Here we report the whole-genome sequencing and analysis of the degu genome, which revealed unique features and molecular adaptations consistent with aging and Alzheimer's disease. We identified single nucleotide polymorphisms in genes associated with Alzheimer's disease including a novel apolipoprotein E (Apoe) gene variant that correlated with an increase in amyloid plaques in brain and modified the in silico predicted degu APOE protein structure and functionality. The reported genome of an unconventional long-lived animal model of aging and Alzheimer's disease offers the opportunity for understanding molecular pathways involved in aging and should help advance biomedical research into treatments for Alzheimer's disease.

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U2 - 10.3389/fnagi.2022.894994

DO - 10.3389/fnagi.2022.894994

M3 - Article

C2 - 35860672

SN - 1663-4365

VL - 14

SP - 894994

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

M1 - 894994

ER -

Genome Sequencing Variations in the Octodon degus, an Unconventional Natural Model of Aging and Alzheimer's Disease

Abstract

Bibliographical note

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