High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains

Abstract Circadian variability is driven by genetics and Diversity Outbred (DO) mice is a powerful tool for examining the genetics of complex traits because their high genetic and phenotypic diversity compared to conventional mouse crosses. The DO population combines the genetic diversity of eight f...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sam-Moon Kim, Chelsea A. Vadnie, Vivek M. Philip, Leona H. Gagnon, Kodavali V. Chowdari, Elissa J. Chesler, Colleen A. McClung, Ryan W. Logan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b12b457980724ac89299756c29d2f1e8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b12b457980724ac89299756c29d2f1e8
record_format	dspace
spelling	oai:doaj.org-article:b12b457980724ac89299756c29d2f1e82021-12-02T13:23:50ZHigh-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains10.1038/s41598-021-82069-82045-2322https://doaj.org/article/b12b457980724ac89299756c29d2f1e82021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82069-8https://doaj.org/toc/2045-2322Abstract Circadian variability is driven by genetics and Diversity Outbred (DO) mice is a powerful tool for examining the genetics of complex traits because their high genetic and phenotypic diversity compared to conventional mouse crosses. The DO population combines the genetic diversity of eight founder strains including five common inbred and three wild-derived strains. In DO mice and their founders, we established a high-throughput system to measure cellular rhythms using in vitro preparations of skin fibroblasts. Among the founders, we observed strong heritability for rhythm period, robustness, phase and amplitude. We also found significant sex and strain differences for these rhythms. Extreme differences in period for molecular and behavioral rhythms were found between the inbred A/J strain and the wild-derived CAST/EiJ strain, where A/J had the longest period and CAST/EiJ had the shortest. In addition, we measured cellular rhythms in 329 DO mice, which displayed far greater phenotypic variability than the founders—80% of founders compared to only 25% of DO mice had periods of ~ 24 h. Collectively, our findings demonstrate that genetic diversity contributes to phenotypic variability in circadian rhythms, and high-throughput characterization of fibroblast rhythms in DO mice is a tractable system for examining the genetics of circadian traits.Sam-Moon KimChelsea A. VadnieVivek M. PhilipLeona H. GagnonKodavali V. ChowdariElissa J. CheslerColleen A. McClungRyan W. LoganNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sam-Moon Kim Chelsea A. Vadnie Vivek M. Philip Leona H. Gagnon Kodavali V. Chowdari Elissa J. Chesler Colleen A. McClung Ryan W. Logan High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains
description	Abstract Circadian variability is driven by genetics and Diversity Outbred (DO) mice is a powerful tool for examining the genetics of complex traits because their high genetic and phenotypic diversity compared to conventional mouse crosses. The DO population combines the genetic diversity of eight founder strains including five common inbred and three wild-derived strains. In DO mice and their founders, we established a high-throughput system to measure cellular rhythms using in vitro preparations of skin fibroblasts. Among the founders, we observed strong heritability for rhythm period, robustness, phase and amplitude. We also found significant sex and strain differences for these rhythms. Extreme differences in period for molecular and behavioral rhythms were found between the inbred A/J strain and the wild-derived CAST/EiJ strain, where A/J had the longest period and CAST/EiJ had the shortest. In addition, we measured cellular rhythms in 329 DO mice, which displayed far greater phenotypic variability than the founders—80% of founders compared to only 25% of DO mice had periods of ~ 24 h. Collectively, our findings demonstrate that genetic diversity contributes to phenotypic variability in circadian rhythms, and high-throughput characterization of fibroblast rhythms in DO mice is a tractable system for examining the genetics of circadian traits.
format	article
author	Sam-Moon Kim Chelsea A. Vadnie Vivek M. Philip Leona H. Gagnon Kodavali V. Chowdari Elissa J. Chesler Colleen A. McClung Ryan W. Logan
author_facet	Sam-Moon Kim Chelsea A. Vadnie Vivek M. Philip Leona H. Gagnon Kodavali V. Chowdari Elissa J. Chesler Colleen A. McClung Ryan W. Logan
author_sort	Sam-Moon Kim
title	High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains
title_short	High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains
title_full	High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains
title_fullStr	High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains
title_full_unstemmed	High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains
title_sort	high-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b12b457980724ac89299756c29d2f1e8
work_keys_str_mv	AT sammoonkim highthroughputmeasurementoffibroblastrhythmsrevealsgeneticheritabilityofcircadianphenotypesindiversityoutbredmiceandtheirfounderstrains AT chelseaavadnie highthroughputmeasurementoffibroblastrhythmsrevealsgeneticheritabilityofcircadianphenotypesindiversityoutbredmiceandtheirfounderstrains AT vivekmphilip highthroughputmeasurementoffibroblastrhythmsrevealsgeneticheritabilityofcircadianphenotypesindiversityoutbredmiceandtheirfounderstrains AT leonahgagnon highthroughputmeasurementoffibroblastrhythmsrevealsgeneticheritabilityofcircadianphenotypesindiversityoutbredmiceandtheirfounderstrains AT kodavalivchowdari highthroughputmeasurementoffibroblastrhythmsrevealsgeneticheritabilityofcircadianphenotypesindiversityoutbredmiceandtheirfounderstrains AT elissajchesler highthroughputmeasurementoffibroblastrhythmsrevealsgeneticheritabilityofcircadianphenotypesindiversityoutbredmiceandtheirfounderstrains AT colleenamcclung highthroughputmeasurementoffibroblastrhythmsrevealsgeneticheritabilityofcircadianphenotypesindiversityoutbredmiceandtheirfounderstrains AT ryanwlogan highthroughputmeasurementoffibroblastrhythmsrevealsgeneticheritabilityofcircadianphenotypesindiversityoutbredmiceandtheirfounderstrains
_version_	1718393174226894848

High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains

Ejemplares similares