A whole-organism landscape of X-inactivation in humans

As females are mosaic for X-inactivation, direct determination of X-linked allelic expression in bulk tissues is typically unfeasible. Using females that are non-mosaic (completely skewed) for X-inactivation (nmXCI) has proven a powerful and natural genetic system for profiling X-inactivation in hum...

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Main Authors: Bjorn Gylemo, Maike Bensberg, Colm E Nestor
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-07-01
Series:eLife
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Online Access:https://elifesciences.org/articles/102701
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author Bjorn Gylemo
Maike Bensberg
Colm E Nestor
author_facet Bjorn Gylemo
Maike Bensberg
Colm E Nestor
author_sort Bjorn Gylemo
collection DOAJ
description As females are mosaic for X-inactivation, direct determination of X-linked allelic expression in bulk tissues is typically unfeasible. Using females that are non-mosaic (completely skewed) for X-inactivation (nmXCI) has proven a powerful and natural genetic system for profiling X-inactivation in humans. By combining allele-resolution data for one previously reported and two newly identified nmXCI females, we directly determined X-inactivation status of 380 X-linked genes across 30 normal tissues, including 198 genes for which XCI status is directly determined for the first time. Our findings represent a substantial advance in our understanding of human X-inactivation and will serve as a reference for dissecting the genetic origin of sex bias in human traits. In addition, our study reveals nmXCI as a common feature of the human female population, with profound consequences for the penetrance and expressivity of X-linked traits in humans.
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spelling doaj-art-9d78a2a3f1854920904ec7f07def40772025-08-20T03:30:37ZengeLife Sciences Publications LtdeLife2050-084X2025-07-011410.7554/eLife.102701A whole-organism landscape of X-inactivation in humansBjorn Gylemo0https://orcid.org/0000-0001-5253-6737Maike Bensberg1https://orcid.org/0000-0003-2395-6083Colm E Nestor2https://orcid.org/0000-0001-5853-1769Crown Princess Victoria Children´s Hospital, Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, SwedenCrown Princess Victoria Children´s Hospital, Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, SwedenCrown Princess Victoria Children´s Hospital, Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, SwedenAs females are mosaic for X-inactivation, direct determination of X-linked allelic expression in bulk tissues is typically unfeasible. Using females that are non-mosaic (completely skewed) for X-inactivation (nmXCI) has proven a powerful and natural genetic system for profiling X-inactivation in humans. By combining allele-resolution data for one previously reported and two newly identified nmXCI females, we directly determined X-inactivation status of 380 X-linked genes across 30 normal tissues, including 198 genes for which XCI status is directly determined for the first time. Our findings represent a substantial advance in our understanding of human X-inactivation and will serve as a reference for dissecting the genetic origin of sex bias in human traits. In addition, our study reveals nmXCI as a common feature of the human female population, with profound consequences for the penetrance and expressivity of X-linked traits in humans.https://elifesciences.org/articles/102701X-inactivationskewed X-inactivationescape from X-inactivation
spellingShingle Bjorn Gylemo
Maike Bensberg
Colm E Nestor
A whole-organism landscape of X-inactivation in humans
eLife
X-inactivation
skewed X-inactivation
escape from X-inactivation
title A whole-organism landscape of X-inactivation in humans
title_full A whole-organism landscape of X-inactivation in humans
title_fullStr A whole-organism landscape of X-inactivation in humans
title_full_unstemmed A whole-organism landscape of X-inactivation in humans
title_short A whole-organism landscape of X-inactivation in humans
title_sort whole organism landscape of x inactivation in humans
topic X-inactivation
skewed X-inactivation
escape from X-inactivation
url https://elifesciences.org/articles/102701
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