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Review
. 2023 Nov 1;31(4):32.
doi: 10.1007/s10577-023-09740-w.

Chromosome instability and aneuploidy in the mammalian brain

Olivia Albert  1 , Shixiang Sun  1 , Anita Huttner  2   3 , Zhengdong Zhang  1 , Yousin Suh  4 , Judith Campisi  5 , Jan Vijg  1   6   7 , Cristina Montagna  8   9
Affiliations
Review

Chromosome instability and aneuploidy in the mammalian brain

Olivia Albert et al. Chromosome Res. .

Abstract

This review investigates the role of aneuploidy and chromosome instability (CIN) in the aging brain. Aneuploidy refers to an abnormal chromosomal count, deviating from the normal diploid set. It can manifest as either a deficiency or excess of chromosomes. CIN encompasses a broader range of chromosomal alterations, including aneuploidy as well as structural modifications in DNA. We provide an overview of the state-of-the-art methodologies utilized for studying aneuploidy and CIN in non-tumor somatic tissues devoid of clonally expanded populations of aneuploid cells.CIN and aneuploidy, well-established hallmarks of cancer cells, are also associated with the aging process. In non-transformed cells, aneuploidy can contribute to functional impairment and developmental disorders. Despite the importance of understanding the prevalence and specific consequences of aneuploidy and CIN in the aging brain, these aspects remain incompletely understood, emphasizing the need for further scientific investigations.This comprehensive review consolidates the present understanding, addresses discrepancies in the literature, and provides valuable insights for future research efforts.

Keywords: Aging; Aneuploidy; Astrocytes; Brain; Cancer; Chromosome instability; Copy number alterations; Disease; Genomic instability; Glioblastoma; Mutation frequency; Mutations; Neurodegeneration; Neurons; Tumor.

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Conflict of interest statement

Conflicts of Interest (CoI)

The authors have no conflict to declare.

Figures

Figure 1:
Figure 1:. Molecular Cytogenetic Techniques commonly used to quantify aneuploidy and large copy number variation.
A) Spectral Karyotyping (SKY) image of metaphase chromosomes illustrating human chromosomes labeled with unique fluorophores or combinations. This allows the identification of all human chromosomes in a single image based on the emission spectra assigned to each autosome or sex chromosome. B-C) Representative interphase nucleus analyzed using interphase FISH (iFISH) to quantify copy number changes to infer chromosome specific aneuploidies. Copy number alterations are determined by enumerating signals at locus-specific probes of interest. A 4-color iFISH approach is employed, utilizing 2-locus specific probes mapping to a single chromosome, which enable the measurement of aneuploidy events (C). D) Representative example of copy number estimates across the entire genome quantified by scL-WGS. After normalizing mappability, GC content, and amplification bias, the results are presented as a copy number variation plot. Each black dot represents a genomic bin, while green horizontal lines indicate regions with 2 copies. Purple regions represent chromosome loss, and red regions represent chromosome gain. The plots were generated using Ginko.
See this image and copyright information in PMC

References

    1. Jacobs KB, Yeager M, Zhou W, Wacholder S, Wang Z, Rodriguez-Santiago B, Hutchinson A, Deng X, Liu C, Horner MJ, Cullen M, Epstein CG, Burdett L, Dean MC, Chatterjee N, Sampson J, Chung CC, Kovaks J, Gapstur SM, Stevens VL, Teras LT, Gaudet MM, Albanes D, Weinstein SJ, Virtamo J, Taylor PR, Freedman ND, Abnet CC, Goldstein AM, Hu N, Yu K, Yuan JM, Liao L, Ding T, Qiao YL, Gao YT, Koh WP, Xiang YB, Tang ZZ, Fan JH, Aldrich MC, Amos C, Blot WJ, Bock CH, Gillanders EM, Harris CC, Haiman CA, Henderson BE, Kolonel LN, Le Marchand L, McNeill LH, Rybicki BA, Schwartz AG, Signorello LB, Spitz MR, Wiencke JK, Wrensch M, Wu X, Zanetti KA, Ziegler RG, Figueroa JD, Garcia-Closas M, Malats N, Marenne G, Prokunina-Olsson L, Baris D, Schwenn M, Johnson A, Landi MT, Goldin L, Consonni D, Bertazzi PA, Rotunno M, Rajaraman P, Andersson U, Beane Freeman LE, Berg CD, Buring JE, Butler MA, Carreon T, Feychting M, Ahlbom A, Gaziano JM, Giles GG, Hallmans G, Hankinson SE, Hartge P, Henriksson R, Inskip PD, Johansen C, Landgren A, McKean-Cowdin R, Michaud DS, Melin BS, Peters U, Ruder AM, Sesso HD, Severi G, Shu XO, Visvanathan K, White E, Wolk A, Zeleniuch-Jacquotte A, Zheng W, Silverman DT, Kogevinas M, Gonzalez JR, Villa O, Li D, Duell EJ, Risch HA, Olson SH, Kooperberg C, Wolpin BM, Jiao L, Hassan M, Wheeler W, Arslan AA, Bueno-de-Mesquita HB, Fuchs CS, Gallinger S, Gross MD, Holly EA, Klein AP, LaCroix A, Mandelson MT, Petersen G, Boutron-Ruault MC, Bracci PM, Canzian F, Chang K, Cotterchio M, Giovannucci EL, Goggins M, Hoffman Bolton JA, Jenab M, Khaw KT, Krogh V, Kurtz RC, McWilliams RR, Mendelsohn JB, Rabe KG, Riboli E, Tjonneland A, Tobias GS, Trichopoulos D, Elena JW, Yu H, Amundadottir L, Stolzenberg-Solomon RZ, Kraft P, Schumacher F, Stram D, Savage SA, Mirabello L, Andrulis IL, Wunder JS, Patino Garcia A, Sierrasesumaga L, Barkauskas DA, Gorlick RG, Purdue M, Chow WH, Moore LE, Schwartz KL, Davis FG, Hsing AW, Berndt SI, Black A, Wentzensen N, Brinton LA, Lissowska J, Peplonska B, McGlynn KA, Cook MB, Graubard BI, Kratz CP, Greene MH, Erickson RL, Hunter DJ, Thomas G, Hoover RN, Real FX, Fraumeni JF Jr., Caporaso NE, Tucker M, Rothman N, Perez-Jurado LA & Chanock SJ Detectable clonal mosaicism and its relationship to aging and cancer. Nature genetics 44, 651–658, doi:10.1038/ng.2270 (2012). - DOI - PMC - PubMed
    1. Costantino I, Nicodemus J & Chun J Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain. Genes (Basel) 12, doi:10.3390/genes12071071 (2021). - DOI - PMC - PubMed
    1. Breuss MW, Yang X, Schlachetzki JCM, Antaki D, Lana AJ, Xu X, Chung C, Chai G, Stanley V, Song Q, Newmeyer TF, Nguyen A, O'Brien S, Hoeksema MA, Cao B, Nott A, McEvoy-Venneri J, Pasillas MP, Barton ST, Copeland BR, Nahas S, Van Der Kraan L, Ding Y, Network NBSM, Glass CK & Gleeson JG Somatic mosaicism reveals clonal distributions of neocortical development. Nature 604, 689–696, doi:10.1038/s41586-022-04602-7 (2022). - DOI - PMC - PubMed
    1. Andriani GA, Vijg J & Montagna C Mechanisms and consequences of aneuploidy and chromosome instability in the aging brain. Mech Ageing Dev, doi:10.1016/j.mad.2016.03.007 (2016). - DOI - PMC - PubMed
    1. Schumacher B, Pothof J, Vijg J & Hoeijmakers JHJ The central role of DNA damage in the ageing process. Nature 592, 695–703, doi:10.1038/s41586-021-03307-7 (2021). - DOI - PMC - PubMed

References (Table1 and 2).

    1. Schröck E, du Manoir S, Veldman T, Schoell B, Wienberg J, Ferguson-Smith MA, Ning Y, Ledbetter DH, Bar-Am I, Soenksen D, Garini Y & Ried T Multicolor spectral karyotyping of human chromosomes. Science 273, 494–497 (1996). - PubMed
    1. Faggioli F, Vijg J & Montagna C Four-color FISH for the detection of low-level aneuploidy in interphase cells. Methods in molecular biology 1136, 291–305, doi:10.1007/978-1-4939-0329-0_14 (2014). - DOI - PubMed
    1. Andriani GA, Maggi E, Pique D, Zimmerman SE, Lee M, Quispe-Tintaya W, Maslov A, Campisi J, Vijg J, Mar JC & Montagna C A direct comparison of interphase FISH versus low-coverage single cell sequencing to detect aneuploidy reveals respective strengths and weaknesses. Scientific reports 9, 10508, doi:10.1038/s41598-019-46606-w (2019). - DOI - PMC - PubMed
    1. Garvin T, Aboukhalil R, Kendall J, Baslan T, Atwal GS, Hicks J, Wigler M & Schatz MC Interactive analysis and assessment of single-cell copy-number variations. Nature methods 12, 1058–1060, doi:10.1038/nmeth.3578 (2015). - DOI - PMC - PubMed
    1. Rehen SK, McConnell MJ, Kaushal D, Kingsbury MA, Yang AH & Chun J Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proceedings of the National Academy of Sciences of the United States of America 98, 13361–13366, doi:10.1073/pnas.231487398 (2001). - DOI - PMC - PubMed

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