Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice

Publication Date:
2018-02-09
Publisher:
Genetics Society of America (GSA)
Electronic ISSN:
2160-1836
Topics:
Biology
Published by:
http://www.genetics-gsa.org/
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autor Maurizio, P. L., Ferris, M. T., Keele, G. R., Miller, D. R., Shaw, G. D., Whitmore, A. C., West, A., Morrison, C. R., Noll, K. E., Plante, K. S., Cockrell, A. S., Threadgill, D. W., Pardo-Manuel de Villena, F., Baric, R. S., Heise, M. T., Valdar, W.
beschreibung Influenza A virus (IAV) is a respiratory pathogen that causes substantial morbidity and mortality during both seasonal and pandemic outbreaks. Infection outcomes in unexposed populations are affected by host genetics, but the host genetic architecture is not well understood. Here, we obtain a broad view of how heritable factors affect a mouse model of response to IAV infection using an 8 x 8 diallel of the eight inbred founder strains of the Collaborative Cross (CC). Expanding on a prior statistical framework for modeling treatment response in diallels, we explore how a range of heritable effects modify acute host response to IAV through 4 d postinfection. Heritable effects in aggregate explained ~57% of the variance in IAV-induced weight loss. Much of this was attributable to a pattern of additive effects that became more prominent through day 4 postinfection and was consistent with previous reports of antiinfluenza myxovirus resistance 1 ( Mx1 ) polymorphisms segregating between these strains; these additive effects largely recapitulated haplotype effects observed at the Mx1 locus in a previous study of the incipient CC, and are also replicated here in a CC recombinant intercross population. Genetic dominance of protective Mx1 haplotypes was observed to differ by subspecies of origin: relative to the domesticus null Mx1 allele, musculus acts dominantly whereas castaneus acts additively. After controlling for Mx1 , heritable effects, though less distinct, accounted for ~34% of the phenotypic variance. Implications for future mapping studies are discussed.
citation_standardnr 6159743
datenlieferant ipn_articles
feed_id 169615
feed_publisher Genetics Society of America (GSA)
feed_publisher_url http://www.genetics-gsa.org/
insertion_date 2018-02-09
journaleissn 2160-1836
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher Genetics Society of America (GSA)
quelle G3: Genes, Genomes, Genetics
relation http://www.g3journal.org/cgi/content/short/8/2/427?rss=1
search_space articles
shingle_author_1 Maurizio, P. L., Ferris, M. T., Keele, G. R., Miller, D. R., Shaw, G. D., Whitmore, A. C., West, A., Morrison, C. R., Noll, K. E., Plante, K. S., Cockrell, A. S., Threadgill, D. W., Pardo-Manuel de Villena, F., Baric, R. S., Heise, M. T., Valdar, W.
shingle_author_2 Maurizio, P. L., Ferris, M. T., Keele, G. R., Miller, D. R., Shaw, G. D., Whitmore, A. C., West, A., Morrison, C. R., Noll, K. E., Plante, K. S., Cockrell, A. S., Threadgill, D. W., Pardo-Manuel de Villena, F., Baric, R. S., Heise, M. T., Valdar, W.
shingle_author_3 Maurizio, P. L., Ferris, M. T., Keele, G. R., Miller, D. R., Shaw, G. D., Whitmore, A. C., West, A., Morrison, C. R., Noll, K. E., Plante, K. S., Cockrell, A. S., Threadgill, D. W., Pardo-Manuel de Villena, F., Baric, R. S., Heise, M. T., Valdar, W.
shingle_author_4 Maurizio, P. L., Ferris, M. T., Keele, G. R., Miller, D. R., Shaw, G. D., Whitmore, A. C., West, A., Morrison, C. R., Noll, K. E., Plante, K. S., Cockrell, A. S., Threadgill, D. W., Pardo-Manuel de Villena, F., Baric, R. S., Heise, M. T., Valdar, W.
shingle_catch_all_1 Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
Influenza A virus (IAV) is a respiratory pathogen that causes substantial morbidity and mortality during both seasonal and pandemic outbreaks. Infection outcomes in unexposed populations are affected by host genetics, but the host genetic architecture is not well understood. Here, we obtain a broad view of how heritable factors affect a mouse model of response to IAV infection using an 8 x 8 diallel of the eight inbred founder strains of the Collaborative Cross (CC). Expanding on a prior statistical framework for modeling treatment response in diallels, we explore how a range of heritable effects modify acute host response to IAV through 4 d postinfection. Heritable effects in aggregate explained ~57% of the variance in IAV-induced weight loss. Much of this was attributable to a pattern of additive effects that became more prominent through day 4 postinfection and was consistent with previous reports of antiinfluenza myxovirus resistance 1 ( Mx1 ) polymorphisms segregating between these strains; these additive effects largely recapitulated haplotype effects observed at the Mx1 locus in a previous study of the incipient CC, and are also replicated here in a CC recombinant intercross population. Genetic dominance of protective Mx1 haplotypes was observed to differ by subspecies of origin: relative to the domesticus null Mx1 allele, musculus acts dominantly whereas castaneus acts additively. After controlling for Mx1 , heritable effects, though less distinct, accounted for ~34% of the phenotypic variance. Implications for future mapping studies are discussed.
Maurizio, P. L., Ferris, M. T., Keele, G. R., Miller, D. R., Shaw, G. D., Whitmore, A. C., West, A., Morrison, C. R., Noll, K. E., Plante, K. S., Cockrell, A. S., Threadgill, D. W., Pardo-Manuel de Villena, F., Baric, R. S., Heise, M. T., Valdar, W.
Genetics Society of America (GSA)
2160-1836
21601836
shingle_catch_all_2 Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
Influenza A virus (IAV) is a respiratory pathogen that causes substantial morbidity and mortality during both seasonal and pandemic outbreaks. Infection outcomes in unexposed populations are affected by host genetics, but the host genetic architecture is not well understood. Here, we obtain a broad view of how heritable factors affect a mouse model of response to IAV infection using an 8 x 8 diallel of the eight inbred founder strains of the Collaborative Cross (CC). Expanding on a prior statistical framework for modeling treatment response in diallels, we explore how a range of heritable effects modify acute host response to IAV through 4 d postinfection. Heritable effects in aggregate explained ~57% of the variance in IAV-induced weight loss. Much of this was attributable to a pattern of additive effects that became more prominent through day 4 postinfection and was consistent with previous reports of antiinfluenza myxovirus resistance 1 ( Mx1 ) polymorphisms segregating between these strains; these additive effects largely recapitulated haplotype effects observed at the Mx1 locus in a previous study of the incipient CC, and are also replicated here in a CC recombinant intercross population. Genetic dominance of protective Mx1 haplotypes was observed to differ by subspecies of origin: relative to the domesticus null Mx1 allele, musculus acts dominantly whereas castaneus acts additively. After controlling for Mx1 , heritable effects, though less distinct, accounted for ~34% of the phenotypic variance. Implications for future mapping studies are discussed.
Maurizio, P. L., Ferris, M. T., Keele, G. R., Miller, D. R., Shaw, G. D., Whitmore, A. C., West, A., Morrison, C. R., Noll, K. E., Plante, K. S., Cockrell, A. S., Threadgill, D. W., Pardo-Manuel de Villena, F., Baric, R. S., Heise, M. T., Valdar, W.
Genetics Society of America (GSA)
2160-1836
21601836
shingle_catch_all_3 Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
Influenza A virus (IAV) is a respiratory pathogen that causes substantial morbidity and mortality during both seasonal and pandemic outbreaks. Infection outcomes in unexposed populations are affected by host genetics, but the host genetic architecture is not well understood. Here, we obtain a broad view of how heritable factors affect a mouse model of response to IAV infection using an 8 x 8 diallel of the eight inbred founder strains of the Collaborative Cross (CC). Expanding on a prior statistical framework for modeling treatment response in diallels, we explore how a range of heritable effects modify acute host response to IAV through 4 d postinfection. Heritable effects in aggregate explained ~57% of the variance in IAV-induced weight loss. Much of this was attributable to a pattern of additive effects that became more prominent through day 4 postinfection and was consistent with previous reports of antiinfluenza myxovirus resistance 1 ( Mx1 ) polymorphisms segregating between these strains; these additive effects largely recapitulated haplotype effects observed at the Mx1 locus in a previous study of the incipient CC, and are also replicated here in a CC recombinant intercross population. Genetic dominance of protective Mx1 haplotypes was observed to differ by subspecies of origin: relative to the domesticus null Mx1 allele, musculus acts dominantly whereas castaneus acts additively. After controlling for Mx1 , heritable effects, though less distinct, accounted for ~34% of the phenotypic variance. Implications for future mapping studies are discussed.
Maurizio, P. L., Ferris, M. T., Keele, G. R., Miller, D. R., Shaw, G. D., Whitmore, A. C., West, A., Morrison, C. R., Noll, K. E., Plante, K. S., Cockrell, A. S., Threadgill, D. W., Pardo-Manuel de Villena, F., Baric, R. S., Heise, M. T., Valdar, W.
Genetics Society of America (GSA)
2160-1836
21601836
shingle_catch_all_4 Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
Influenza A virus (IAV) is a respiratory pathogen that causes substantial morbidity and mortality during both seasonal and pandemic outbreaks. Infection outcomes in unexposed populations are affected by host genetics, but the host genetic architecture is not well understood. Here, we obtain a broad view of how heritable factors affect a mouse model of response to IAV infection using an 8 x 8 diallel of the eight inbred founder strains of the Collaborative Cross (CC). Expanding on a prior statistical framework for modeling treatment response in diallels, we explore how a range of heritable effects modify acute host response to IAV through 4 d postinfection. Heritable effects in aggregate explained ~57% of the variance in IAV-induced weight loss. Much of this was attributable to a pattern of additive effects that became more prominent through day 4 postinfection and was consistent with previous reports of antiinfluenza myxovirus resistance 1 ( Mx1 ) polymorphisms segregating between these strains; these additive effects largely recapitulated haplotype effects observed at the Mx1 locus in a previous study of the incipient CC, and are also replicated here in a CC recombinant intercross population. Genetic dominance of protective Mx1 haplotypes was observed to differ by subspecies of origin: relative to the domesticus null Mx1 allele, musculus acts dominantly whereas castaneus acts additively. After controlling for Mx1 , heritable effects, though less distinct, accounted for ~34% of the phenotypic variance. Implications for future mapping studies are discussed.
Maurizio, P. L., Ferris, M. T., Keele, G. R., Miller, D. R., Shaw, G. D., Whitmore, A. C., West, A., Morrison, C. R., Noll, K. E., Plante, K. S., Cockrell, A. S., Threadgill, D. W., Pardo-Manuel de Villena, F., Baric, R. S., Heise, M. T., Valdar, W.
Genetics Society of America (GSA)
2160-1836
21601836
shingle_title_1 Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
shingle_title_2 Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
shingle_title_3 Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
shingle_title_4 Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
timestamp 2025-06-30T23:32:35.981Z
titel Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
titel_suche Bayesian Diallel Analysis Reveals Mx1-Dependent and Mx1-Independent Effects on Response to Influenza A Virus in Mice
topic W
uid ipn_articles_6159743