Insights into the loss of the Y chromosome with age in control individuals and in patients with age-related macular degeneration using genotyping microarray data

International AMD Genomics Consortium (IAMDGC)

doi:10.1007/s00439-019-02029-1

Insights into the loss of the Y chromosome with age in control individuals and in patients with age-related macular degeneration using genotyping microarray data

International AMD Genomics Consortium (IAMDGC)

Medical Sciences

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

16 Citations (Scopus)

Abstract

The extent of aneuploidy of the sex chromosomes increases with age in human leukocytes. Here, we re-explore the dynamics of normal loss of the Y chromosome (LOY) with age based on microarray data using two exponential models and two different ways to estimate the fraction of LOY. This analysis shows the existence of a significant correlation between the fraction of LOY estimated from molecular cytogenetics and genotyping microarray data. Although the specific estimates of the parameters for the two exponential models are different from those derived from cytogenetics data, the present analysis in an independent dataset of normal individuals confirms that X0 cells have a selective advantage over XY cells. Moreover, patients with age-related macular degeneration display higher fraction of LOY values and seem to have a predisposition to lose their Y chromosome even at young ages compared to control individuals. As there are no data available for the same individuals at different time points, the parameters reported here are average values drawn from population analyses.

Original language	English
Pages (from-to)	401-407
Number of pages	7
Journal	Human Genetics
Volume	139
Early online date	27 May 2019
DOIs	https://doi.org/10.1007/s00439-019-02029-1
Publication status	Published - Mar 2020

Bibliographical note

Acknowledgements: This work was supported by the University Paris Diderot, by the Centre National de la Recherche Scientifique and from the Fondation pour la Recherche Médicale Grant: (DEQ 20150331757).

Funding: This work was supported by the University Paris Diderot, by the Centre National de la Recherche Scientifique, from the Fondation pour la Recherche Médicale Grant: (DEQ 20150331757) and by institutional funds of the Institute of Human Genetics, University of Regensburg (TG77 to BHFW). Genotyping was conducted as part of the IAMDGC exome-chip project supported by CIDR (Contract number HHSN268201200008I) and funded by EY022310 (to Jonathan L. Haines, Case Western Reserve University, Cleveland) and 1X01HG006934-01 (to Gonçalo R. Abecasis, University of Michigan, Department of Biostatistics).

Keywords

Aging/genetics
Aneuploidy
Chromosome Deletion
Chromosomes, Human, Y/genetics
Genotype
Humans
Leukocytes/physiology
Macular Degeneration/genetics
Male
RISK
MOSAIC LOSS
GENETICS
MEN
COMMON
BLOOD

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@article{f44640b726c24c749679bbd45630b281,

title = "Insights into the loss of the Y chromosome with age in control individuals and in patients with age-related macular degeneration using genotyping microarray data",

abstract = "The extent of aneuploidy of the sex chromosomes increases with age in human leukocytes. Here, we re-explore the dynamics of normal loss of the Y chromosome (LOY) with age based on microarray data using two exponential models and two different ways to estimate the fraction of LOY. This analysis shows the existence of a significant correlation between the fraction of LOY estimated from molecular cytogenetics and genotyping microarray data. Although the specific estimates of the parameters for the two exponential models are different from those derived from cytogenetics data, the present analysis in an independent dataset of normal individuals confirms that X0 cells have a selective advantage over XY cells. Moreover, patients with age-related macular degeneration display higher fraction of LOY values and seem to have a predisposition to lose their Y chromosome even at young ages compared to control individuals. As there are no data available for the same individuals at different time points, the parameters reported here are average values drawn from population analyses.",

keywords = "Aging/genetics, Aneuploidy, Chromosome Deletion, Chromosomes, Human, Y/genetics, Genotype, Humans, Leukocytes/physiology, Macular Degeneration/genetics, Male, RISK, MOSAIC LOSS, GENETICS, MEN, COMMON, BLOOD",

author = "Felix Grassmann and Weber, {Bernhard H.F.} and Veitia, {Reiner A.} and {International AMD Genomics Consortium (IAMDGC)}",

note = "Acknowledgements: This work was supported by the University Paris Diderot, by the Centre National de la Recherche Scientifique and from the Fondation pour la Recherche M{\'e}dicale Grant: (DEQ 20150331757). Funding: This work was supported by the University Paris Diderot, by the Centre National de la Recherche Scientifique, from the Fondation pour la Recherche M{\'e}dicale Grant: (DEQ 20150331757) and by institutional funds of the Institute of Human Genetics, University of Regensburg (TG77 to BHFW). Genotyping was conducted as part of the IAMDGC exome-chip project supported by CIDR (Contract number HHSN268201200008I) and funded by EY022310 (to Jonathan L. Haines, Case Western Reserve University, Cleveland) and 1X01HG006934-01 (to Gon{\c c}alo R. Abecasis, University of Michigan, Department of Biostatistics).",

year = "2020",

month = mar,

doi = "10.1007/s00439-019-02029-1",

language = "English",

volume = "139",

pages = "401--407",

journal = "Human Genetics",

issn = "0340-6717",

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T1 - Insights into the loss of the Y chromosome with age in control individuals and in patients with age-related macular degeneration using genotyping microarray data

AU - Grassmann, Felix

AU - Weber, Bernhard H.F.

AU - Veitia, Reiner A.

AU - International AMD Genomics Consortium (IAMDGC)

N1 - Acknowledgements: This work was supported by the University Paris Diderot, by the Centre National de la Recherche Scientifique and from the Fondation pour la Recherche Médicale Grant: (DEQ 20150331757). Funding: This work was supported by the University Paris Diderot, by the Centre National de la Recherche Scientifique, from the Fondation pour la Recherche Médicale Grant: (DEQ 20150331757) and by institutional funds of the Institute of Human Genetics, University of Regensburg (TG77 to BHFW). Genotyping was conducted as part of the IAMDGC exome-chip project supported by CIDR (Contract number HHSN268201200008I) and funded by EY022310 (to Jonathan L. Haines, Case Western Reserve University, Cleveland) and 1X01HG006934-01 (to Gonçalo R. Abecasis, University of Michigan, Department of Biostatistics).

PY - 2020/3

Y1 - 2020/3

N2 - The extent of aneuploidy of the sex chromosomes increases with age in human leukocytes. Here, we re-explore the dynamics of normal loss of the Y chromosome (LOY) with age based on microarray data using two exponential models and two different ways to estimate the fraction of LOY. This analysis shows the existence of a significant correlation between the fraction of LOY estimated from molecular cytogenetics and genotyping microarray data. Although the specific estimates of the parameters for the two exponential models are different from those derived from cytogenetics data, the present analysis in an independent dataset of normal individuals confirms that X0 cells have a selective advantage over XY cells. Moreover, patients with age-related macular degeneration display higher fraction of LOY values and seem to have a predisposition to lose their Y chromosome even at young ages compared to control individuals. As there are no data available for the same individuals at different time points, the parameters reported here are average values drawn from population analyses.

AB - The extent of aneuploidy of the sex chromosomes increases with age in human leukocytes. Here, we re-explore the dynamics of normal loss of the Y chromosome (LOY) with age based on microarray data using two exponential models and two different ways to estimate the fraction of LOY. This analysis shows the existence of a significant correlation between the fraction of LOY estimated from molecular cytogenetics and genotyping microarray data. Although the specific estimates of the parameters for the two exponential models are different from those derived from cytogenetics data, the present analysis in an independent dataset of normal individuals confirms that X0 cells have a selective advantage over XY cells. Moreover, patients with age-related macular degeneration display higher fraction of LOY values and seem to have a predisposition to lose their Y chromosome even at young ages compared to control individuals. As there are no data available for the same individuals at different time points, the parameters reported here are average values drawn from population analyses.

KW - Aging/genetics

KW - Aneuploidy

KW - Chromosome Deletion

KW - Chromosomes, Human, Y/genetics

KW - Genotype

KW - Humans

KW - Leukocytes/physiology

KW - Macular Degeneration/genetics

KW - Male

KW - RISK

KW - MOSAIC LOSS

KW - GENETICS

KW - MEN

KW - COMMON

KW - BLOOD

UR - http://www.scopus.com/inward/record.url?scp=85071846024&partnerID=8YFLogxK

U2 - 10.1007/s00439-019-02029-1

DO - 10.1007/s00439-019-02029-1

M3 - Article

C2 - 31134332

AN - SCOPUS:85071846024

SN - 0340-6717

VL - 139

SP - 401

EP - 407

JO - Human Genetics

JF - Human Genetics

ER -

Insights into the loss of the Y chromosome with age in control individuals and in patients with age-related macular degeneration using genotyping microarray data

Abstract

Bibliographical note

Keywords

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