Biphasic survival analysis of trypanotolerance QTL in mice

A marker-assisted introgression (MAI) experiment was conducted to transfer trypanotolerance quantitative trait loci (QTL) from a donor mouse strain, C57BL/6, into a recipient mouse strain, A/J. The objective was to assess the effect of three previously identified chromosomal regions on mouse chromos...

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Autores principales: Koudande, O.D., Thomson, P.C., Bovenhuis, H., Iraqi, F.A., Gibson, John P., Arendonk, Johan A.M. van
Formato: Journal Article
Lenguaje:Inglés
Publicado: Springer 2008
Materias:
Acceso en línea:https://hdl.handle.net/10568/32934
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author Koudande, O.D.
Thomson, P.C.
Bovenhuis, H.
Iraqi, F.A.
Gibson, John P.
Arendonk, Johan A.M. van
author_browse Arendonk, Johan A.M. van
Bovenhuis, H.
Gibson, John P.
Iraqi, F.A.
Koudande, O.D.
Thomson, P.C.
author_facet Koudande, O.D.
Thomson, P.C.
Bovenhuis, H.
Iraqi, F.A.
Gibson, John P.
Arendonk, Johan A.M. van
author_sort Koudande, O.D.
collection Repository of Agricultural Research Outputs (CGSpace)
description A marker-assisted introgression (MAI) experiment was conducted to transfer trypanotolerance quantitative trait loci (QTL) from a donor mouse strain, C57BL/6, into a recipient mouse strain, A/J. The objective was to assess the effect of three previously identified chromosomal regions on mouse chromosomes 1 (MMU1), 5 (MMU5) and 17 (MMU17) in different genetic backgrounds on the survival pattern following infection with Trypanosoma congolense. An exploratory data analysis revealed a biphasic pattern of time to death, with highly distinct early and late mortality phases. In this paper, we present survival analysis methods that account for the biphasic mortality pattern and results of reanalyzing the data from the MAI experiment. The analysis with a Weibull mixture model confirmed the biphasic pattern of time to death. Mortality phase, an unobserved variable, appears to be an important factor influencing survival time and is modeled as a binary outcome variable using logistic regression analysis. Accounting for this biphasic pattern in the analysis reveals that a previously observed sex effect on average survival is rather an effect on proportion of mice in the two mortality phases. The C57BL/6 (donor) QTL alleles on MMU1 and MMU17 act dominantly in the late mortality phase while the A/J (recipient) QTL allele on MMU17 acts dominantly in the early mortality phase. From this study, we found clear evidence for a biphasic survival pattern and provided models for its analysis. These models can also be used when studying defense mechanisms against other pathogens. Finally, these approaches provide further information on the nature of gene actions.
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spelling CGSpace329342023-12-08T19:36:04Z Biphasic survival analysis of trypanotolerance QTL in mice Koudande, O.D. Thomson, P.C. Bovenhuis, H. Iraqi, F.A. Gibson, John P. Arendonk, Johan A.M. van trypanosomiasis disease resistance mice chromosomes mortality genes genetics A marker-assisted introgression (MAI) experiment was conducted to transfer trypanotolerance quantitative trait loci (QTL) from a donor mouse strain, C57BL/6, into a recipient mouse strain, A/J. The objective was to assess the effect of three previously identified chromosomal regions on mouse chromosomes 1 (MMU1), 5 (MMU5) and 17 (MMU17) in different genetic backgrounds on the survival pattern following infection with Trypanosoma congolense. An exploratory data analysis revealed a biphasic pattern of time to death, with highly distinct early and late mortality phases. In this paper, we present survival analysis methods that account for the biphasic mortality pattern and results of reanalyzing the data from the MAI experiment. The analysis with a Weibull mixture model confirmed the biphasic pattern of time to death. Mortality phase, an unobserved variable, appears to be an important factor influencing survival time and is modeled as a binary outcome variable using logistic regression analysis. Accounting for this biphasic pattern in the analysis reveals that a previously observed sex effect on average survival is rather an effect on proportion of mice in the two mortality phases. The C57BL/6 (donor) QTL alleles on MMU1 and MMU17 act dominantly in the late mortality phase while the A/J (recipient) QTL allele on MMU17 acts dominantly in the early mortality phase. From this study, we found clear evidence for a biphasic survival pattern and provided models for its analysis. These models can also be used when studying defense mechanisms against other pathogens. Finally, these approaches provide further information on the nature of gene actions. 2008-04 2013-07-03T05:25:47Z 2013-07-03T05:25:47Z Journal Article https://hdl.handle.net/10568/32934 en Open Access Springer Heredity;100(4): 407-414
spellingShingle trypanosomiasis
disease resistance
mice
chromosomes
mortality
genes
genetics
Koudande, O.D.
Thomson, P.C.
Bovenhuis, H.
Iraqi, F.A.
Gibson, John P.
Arendonk, Johan A.M. van
Biphasic survival analysis of trypanotolerance QTL in mice
title Biphasic survival analysis of trypanotolerance QTL in mice
title_full Biphasic survival analysis of trypanotolerance QTL in mice
title_fullStr Biphasic survival analysis of trypanotolerance QTL in mice
title_full_unstemmed Biphasic survival analysis of trypanotolerance QTL in mice
title_short Biphasic survival analysis of trypanotolerance QTL in mice
title_sort biphasic survival analysis of trypanotolerance qtl in mice
topic trypanosomiasis
disease resistance
mice
chromosomes
mortality
genes
genetics
url https://hdl.handle.net/10568/32934
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