Browsing by Author "Honaker, Christa F."

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    Association of MHCY genotypes in lines of chickens divergently selected for high or low antibody response to sheep red blood cells
    Zhang, Jibin; Goto, Ronald M.; Honaker, Christa F.; Siegel, Paul B.; Taylor, Robert L.; Parmentier, Henk K.; Miller, Marcia M. (Elsevier, 2022-03)
    The chicken MHCY region contains members of several gene families including a family of highly polymorphic MHC class I genes that are structurally distinct from their classical class I gene counterparts. Genetic variability at MHCY could impart variability in immune responses, but robust tests for whether or not this occurs have been lacking. Here we defined the MHCY genotypes present in 2 sets of chicken lines selected for high or low antibody response, the Virginia Tech (VT) HAS and LAS, and the Wageningen University (WU) HA and LA lines. Both sets were developed under long-term bidirectional selection for differences in antibody responses following immunization with the experimental antigen sheep red blood cells. Lines in which selection was relaxed (VT HAR and LAR) or lacking (WU C) provided controls. We looked for evidence of association between MHCY genotypes and antibody titers. Chickens were typed for MHCY using a recently developed method based on a multilocus short tandem repeat sequence found across MHCY haplotypes. Five MHCY haplotypes were found segregating in the VT HAS and LAS lines. One haplotype was present only in HAS chickens, and another was present only in LAS chickens with distribution of the remaining 3 haplotypes differing significantly between the lines. In the WU HA and LA lines, there was a similar MHCY asymmetry. The control populations lacked similar asymmetries. These observations support the likelihood of MHCY genetics affecting heritable antibody responses and provide a basis for further investigations into the role of MHCY region genes in guiding immune responses in chickens.
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    Bidirectional Selection for Body Weight on Standing Genetic Variation in a Chicken Model
    Lillie, Mette; Honaker, Christa F.; Siegel, Paul B.; Carlborg, Örjan (Genetics Society of America, 2019-04)
    Experimental populations of model organisms provide valuable opportunities to unravel the genomic impact of selection in a controlled system. The Virginia body weight chicken lines represent a unique resource to investigate signatures of selection in a system where long-term, single-trait, bidirectional selection has been carried out for more than 60 generations. At 55 generations of divergent selection, earlier analyses of pooled genome resequencing data from these lines revealed that 14.2% of the genome showed extreme differentiation between the selected lines, contained within 395 genomic regions. Here, we report more detailed analyses of these data exploring the regions displaying within- and between-line genomic signatures of the bidirectional selection applied in these lines. Despite the strict selection regime for opposite extremes in body weight, this did not result in opposite genomic signatures between the lines. The lines often displayed a duality of the sweep signatures, where an extended region of homozygosity in one line, in contrast to mosaic pattern of heterozygosity in the other line. These haplotype mosaics consisted of short, distinct haploblocks of variable between-line divergence, likely the results of a complex demographic history involving bottlenecks, introgressions and moderate inbreeding. We demonstrate this using the example of complex haplotype mosaicism in the growth1 QTL. These mosaics represent the standing genetic variation available at the onset of selection in the founder population. Selection on standing genetic variation can thus result in different signatures depending on the intensity and direction of selection.
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    Body Weight Selection Affects Quantitative Genetic Correlated Responses in Gut Microbiota
    Meng, He; Zhang, Yan; Zhao, Lele; Zhao, Wenjing; He, Chuan; Honaker, Christa F.; Zhai, Zhengxiao; Sun, Zikui; Siegel, Paul B. (PLOS, 2014-03-07)
    The abundance of gut microbiota can be viewed as a quantitative trait, which is affected by the genetics and environment of the host. To quantify the effects of host genetics, we calculated the heritability of abundance of specific microorganisms and genetic correlations among them in the gut microbiota of two lines of chickens maintained under the same husbandry and dietary regimes. The lines, which originated from a common founder population, had undergone >50 generations of selection for high (HW) or low (LW) 56-day body weight and now differ by more than 10-fold in body weight at selection age. We identified families of Paenibacillaceae, Streptococcaceae, Helicobacteraceae, and Burkholderiaceae that had moderate heritabilities. Although there were no obvious phenotypic correlations among gut microbiota, significant genetic correlations were observed. Moreover, the effects were modified by genetic selection for body weight, which altered the quantitative genetic background of the host. Heritabilities for Bacillaceae, Flavobacteriaceae, Helicobacteraceae, Comamonadaceae, Enterococcaceae, and Streptococcaceae were moderate in LW line and little to zero in the HW line. These results suggest that loci associated with these microbiota families, while exhibiting genetic variation in LW, have been fixed in HW line. Also, long term selection for body weight has altered the genetic correlations among gut microbiota. No microbiota families had significant heritabilities in both the LW and HW lines suggesting that the presence and/or absence of a particular microbiota family either has a strong growth promoting or inhibiting effect, but not both. These results demonstrate that the quantitative genetics of the host have considerable influence on the gut microbiota.
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    Dynamics of Small Non-coding RNA Profiles and the Intestinal Microbiome of High and Low Weight Chickens
    Zhou, Hao; Yang, Lingyu; Ding, Jinmei; Xu, Ke; Liu, Jiajia; Zhu, Wenqi; Zhu, Jianshen; He, Chuan; Han, Chengxiao; Qin, Chao; Luo, Huaixi; Chen, Kangchun; Zheng, Yuming; Honaker, Christa F.; Zhang, Yan; Siegel, Paul B.; Meng, He (Frontiers, 2022-06-30)
    The host and its symbiotic bacteria form a biological entity, holobiont, in which they share a dynamic connection characterized by symbiosis, co-metabolism, and coevolution. However, how these collaborative relationships were maintained over evolutionary time remains unclear. In this research, the small non-coding RNA (sncRNA) profiles of cecum and their bacteria contents were measured from lines of chickens that have undergone long-term selection for high (HWS) or low (LWS) 56-day body weight. The results from these lines that originated from a common founder population and maintained under the same husbandry showed an association between host intestinal sncRNA expression profile (miRNA, lncRNA fragment, mRNA fragment, snoRNA, and snRNA) and intestinal microbiota. Correlation analyses suggested that some central miRNAs and mRNA fragments had interactions with the abundance of intestinal microbial species and microbiota functions. miR-6622-3p, a significantly differentially expressed (DE) miRNA was correlated with a body weight gain related bacterium, Alistipes putredinis. Our results showed that host sncRNAs may be mediators of interaction between the host and its intestinal microbiome. This provides additional clue for holobiont concepts.
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    Genome-wide standing variation facilitates long-term response to bidirectional selection for antibody response in chickens
    Lillie, Mette; Sheng, Zheya; Honaker, Christa F.; Dorshorst, Benjamin J.; Ashwell, Christopher M.; Siegel, Paul B.; Carlborg, Örjan (2017-01-18)
    Background Long-term selection experiments provide a powerful approach to gain empirical insights into adaptation, allowing researchers to uncover the targets of selection and infer their contributions to the mode and tempo of adaptation. Here we implement a pooled genome re-sequencing approach to investigate the consequences of 39 generations of bidirectional selection in White Leghorn chickens on a humoral immune trait: antibody response to sheep red blood cells. Results We observed wide genome involvement in response to this selection regime. Many genomic regions were highly differentiated resulting from this experimental selection regime, an involvement of up to 20% of the chicken genome (208.8 Mb). While genetic drift has certainly contributed to this, we implement gene ontology, association analysis and population simulations to increase our confidence in candidate selective sweeps. Three strong candidate genes, MHC, SEMA5A and TGFBR2, are also presented. Conclusions The extensive genomic changes highlight the polygenic genetic architecture of antibody response in these chicken populations, which are derived from a common founder population, demonstrating the extent of standing immunogenetic variation available at the onset of selection.
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    Genotyping by low-coverage whole-genome sequencing in intercross pedigrees from outbred founders: a cost-efficient approach
    Zan, Yanjun; Payen, Thibaut; Lillie, Mette; Honaker, Christa F.; Siegel, Paul B.; Carlborg, Örjan (2019-08-14)
    Background Experimental intercrosses between outbred founder populations are powerful resources for mapping loci that contribute to complex traits i.e. quantitative trait loci (QTL). Here, we present an approach and its accompanying software for high-resolution reconstruction of founder mosaic genotypes in the intercross offspring from such populations using whole-genome high-coverage sequence data on founder individuals (~ 30×) and very low-coverage sequence data on intercross individuals (< 0.5×). Sets of founder-line informative markers were selected for each full-sib family and used to infer the founder mosaic genotypes of the intercross individuals. The application of this approach and the quality of the estimated genome-wide genotypes are illustrated in a large F2 pedigree between two divergently selected lines of chickens. Results We describe how we obtained whole-genome genotype data for hundreds of individuals in a cost- and time-efficient manner by using a Tn5-based library preparation protocol and an imputation algorithm that was optimized for this application. In total, 7.6 million markers segregated in this pedigree and, within each full-sib family, between 10.0 and 13.7% of these were fully informative, i.e. fixed for alternative alleles in the founders from the divergent lines, and were used for reconstruction of the offspring mosaic genotypes. The genotypes that were estimated based on the low-coverage sequence data were highly consistent (> 95% agreement) with those obtained using individual single nucleotide polymorphism (SNP) genotyping. The estimated resolution of the inferred recombination breakpoints was relatively high, with 50% of them being defined on regions shorter than 10 kb. Conclusions A method and software for inferring founder mosaic genotypes in intercross offspring from low-coverage whole-genome sequencing in pedigrees from heterozygous founders are described. They provide high-quality, high-resolution genotypes in a time- and cost-efficient manner. The software is freely available at https://github.com/CarlborgGenomics/Stripes.
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    Glucose Tolerance and Plasma Non-Esterified Fatty Acid Levels in Chickens Selected for Low Body Weight, Red Junglefowl, and their Reciprocal Cross
    Sutherland, Dez-Ann A. T.; Honaker, Christa F.; Gilbert, Elizabeth R.; Andersson, Leif; Siegel, Paul B. (Japan Poultry Science Association, 2019-10-01)
    Responses of an individual to food deprivation, such as a 16-h fast, are complex, and are influenced by environmental and genetic factors. Domestication is an ongoing process during which adaptations to changing environments occur over generations. Food deprivation by their caretakers is less for domestic chickens than for their junglefowl ancestors. Unlike domestic chicken, the junglefowl adapted over generations to periods of food deprivation, which may be reflected in differences in metabolic responses to brief periods without food. Here, we compared the blood glucose and plasma levels of non-esterified fatty acids (NEFA) among four populations when deprived of feed for 16 h. The four populations included a domestic White Rock experimental line (LWS) maintained for generations under ad libitum feeding, adult red junglefowl (RJF), and a reciprocal cross of the lines. Although there were significant differences in adult (31-week) body weight between the RJF (683 g) and LWS (1282 g), with the weight of F1 crosses being intermediate, the amount of abdominal fat relative to body weight was similar for all populations. Patterns for blood glucose responses to a glucose bolus after a 16-h fast were similar for the initial and final points in the parental and cross populations. However, RJF reached their peak faster than LWS, with the reciprocal cross intermediate to the parental populations. Plasma NEFA concentrations were higher after the 16-h fast than in fed states, with no population differences for the fasting state. However, in the fed state, NEFA levels were lesser for LWS than for others, which was reflected further in percentage change from fed to fasted. This larger change in LWS suggests differences in mobilization of energy substrates and implies that during domestication or development of the LWS line, thresholds for responses to acute stressors may have increased.
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    Growth of White Leghorn Chicken Immune Organs after Long-Term Divergent Selection for High or Low Antibody Response to Sheep Red Blood Cells
    Honaker, Christa F.; Taylor, Robert L.; Edens, Frank W.; Siegel, Paul B. (MDPI, 2024-05-17)
    Long-term divergent selection from a common founder population for a single trait—antibody response to sheep erythrocytes 5 days post-injection—has resulted in two distinct lines of White Leghorn chickens with a well-documented difference in antibody titers: high (HAS)- and low (LAS)-antibody selected lines. Subpopulations—high (HAR)- and low (LAR)-antibody relaxed—were developed from generation 24 of the selected lines to relax selection. The objective of the current experiment was to determine if this long-term selection and relaxation of selection impacted the growth of two organs important to chicken immunity: the spleen and the bursa of Fabricius. Spleens and bursae were obtained from ten chickens per line at nine timepoints (E18, D0, D6, D13, D20, D35, D49, D63, and D91) throughout their rapid growth phase and presented as a percent of body weight. Significance was set at p ≤ 0.05. For the spleen, all lines consistently increased in size relative to body weight to D49, followed by a consistent decline. All lines had a similar growth pattern, but HAS spleens grew faster than LAS spleens. For the bursa, LAS was smaller than the other three lines as an embryo and also smaller than HAS through D63. In the selected lines, bursa weight peaked at D35, whereas the relaxed lines peaked at D49. By D91, there was no difference between lines. Artificial and natural selection, represented by the long-term selected and relaxed antibody lines, resulted in differences in the growth patterns and relative weights of the spleen and bursa of Fabricius.
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    Gut Microbiota Co-microevolution with Selection for Host Humoral Immunity
    Yang, Lingyu; Liu, Shuyun; Ding, Jinmei; Dai, Ronghua; He, Chuan; Xu, Ke; Honaker, Christa F.; Zhang, Yan; Siegel, Paul B.; Meng, He (Frontiers, 2017-07-04)
    To explore coevolution between the gut microbiota and the humoral immune system of the host, we used chickens as the model organism. The host populations were two lines (HAS and LAS) developed from a common founder that had undergone 40 generations of divergent selection for antibody titers to sheep red blood cells (SRBC) and two relaxed sublines (HAR and LAR). Analysis revealed that microevolution of host humoral immunity contributed to the composition of gut microbiota at the taxa level. Relaxing selection enriched some microorganisms whose functions were opposite to host immunity. Particularly, Ruminococcaceae and Oscillospira enriched in high antibody relaxed (HAR) and contributed to reduction in antibody response, while Lactobacillus increased in low antibody relaxed (LAR) and elevated the antibody response. Microbial functional analysis showed that alterations were involved in pathways relating to the immune system and infectious diseases. Our findings demonstrated co-microevolution relationships of host-microbiota and that gut microorganisms influenced host immunity.
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    Haplotype Purging after Relaxation of Selection in Lines of Chickens That Had Undergone Long-Term Selection for High and Low Body Weight
    Yang, Yunzhou; Zan, Yanjun; Honaker, Christa F.; Siegel, Paul B.; Carlborg, Örjan (MDPI, 2020-06-08)
    Bi-directional selection for increased and decreased 56-day body weights (BW56) has been applied to two lines of White Plymouth Rock chickens—the Virginia high (HWS) and low (LWS) body weight lines. Correlated responses have been observed, including negative effects on traits related to fitness. Here, we use high and low body weight as proxies for fitness. On a genome-wide level, relaxed lines (HWR, LWR) bred from HWS and LWS purged some genetic variants in the selected lines. Whole-genome re-sequencing was here used to identify individual loci where alleles that accumulated during directional selection were purged when selection was relaxed. In total, 11 loci with significant purging signals were identified, five in the low (LW) and six in the high (HW) body weight lineages. Associations between purged haplotypes in these loci and BW56 were tested in an advanced intercross line (AIL). Two loci with purging signals and haplotype associations to BW56 are particularly interesting for further functional characterization, one locus on chromosome 6 in the LW covering the sour-taste receptor gene PKD2L1, a functional candidate gene for the decreased appetite observed in the LWS and a locus on chromosome 20 in the HW containing a skeletal muscle hypertrophy gene, DNTTIP1.
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    Imputation-Based Fine-Mapping Suggests That Most QTL in an Outbred Chicken Advanced Intercross Body Weight Line Are Due to Multiple, Linked Loci
    Brandt, Monika; Ahsan, Muhammad; Honaker, Christa F.; Siegel, Paul B.; Carlborg, Örjan (Genetics Society of America, 2017-01)
    The Virginia chicken lines have been divergently selected for juvenile body weight for more than 50 generations. Today, the high-and low-weight lines show a >12-fold difference for the selected trait, 56-d body weight. These lines provide unique opportunities to study the genetic architecture of long-term, single-trait selection. Previously, several quantitative trait loci (QTL) contributing to weight differences between the lines were mapped in an F-2-cross between them, and these were later replicated and fine-mapped in a nine-generation advanced intercross of them. Here, we explore the possibility to further increase the fine-mapping resolution of these QTL via a pedigree-based imputation strategy that aims to better capture the genetic diversity in the divergently selected, but outbred, founder lines. The founders of the intercross were high-density genotyped, and then pedigree-based imputation was used to assign genotypes throughout the pedigree. Imputation increased the marker density 20-fold in the selected QTL, providing 6911 markers for the subsequent analysis. Both single-marker association and multi-marker backward-elimination analyses were used to explore regions associated with 56-d body weight. The approach revealed several statistically and population structure independent associations and increased the mapping resolution. Further, most QTL were also found to contain multiple independent associations to markers that were not fixed in the founder populations, implying a complex underlying architecture due to the combined effects of multiple, linked loci perhaps located on independent haplotypes that still segregate in the selected lines.
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    Pathogenesis and shedding of Usutu virus in juvenile chickens
    Kuchinsky, Sarah C.; Frere, Francesca; Heitzman-Breen, Nora; Golden, Jacob; Vázquez, Ana; Honaker, Christa F.; Siegel, Paul B.; Ciupe, Stanca M.; LeRoith, Tanya; Duggal, Nisha K. (Taylor & Francis, 2021-01-01)
    Usutu virus (USUV; family: Flaviviridae, genus: Flavivirus), is an emerging zoonotic arbovirus that causes severe neuroinvasive disease in humans and has been implicated in the loss of breeding bird populations in Europe. USUV is maintained in an enzootic cycle between ornithophilic mosquitos and wild birds. As a member of the Japanese encephalitis serocomplex, USUV is closely related to West Nile virus (WNV) and St. Louis encephalitis virus (SLEV), both neuroinvasive arboviruses endemic in wild bird populations in the United States. An avian model for USUV is essential to understanding zoonotic transmission. Here we describe the first avian models of USUV infection with the development of viremia. Juvenile commercial ISA Brown chickens were susceptible to infection by multiple USUV strains with evidence of cardiac lesions. Juvenile chickens from two chicken lines selected for high (HAS) or low (LAS) antibody production against sheep red blood cells showed markedly different responses to USUV infection. Morbidity and mortality were observed in the LAS chickens, but not HAS chickens. LAS chickens had significantly higher viral titers in blood and other tissues, as well as oral secretions, and significantly lower development of neutralizing antibody responses compared to HAS chickens. Mathematical modelling of virus-host interactions showed that the viral clearance rate is a stronger mitigating factor for USUV viremia than neutralizing antibody response in this avian model. These chicken models provide a tool for further understanding USUV pathogenesis in birds and evaluating transmission dynamics between avian hosts and mosquito vectors.
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    Standing genetic variation as a major contributor to adaptation in the Virginia chicken lines selection experiment
    Sheng, Zheya; Pettersson, Mats E.; Honaker, Christa F.; Siegel, Paul B.; Carlborg, Örjan (2015-10-01)
    Background Artificial selection provides a powerful approach to study the genetics of adaptation. Using selective-sweep mapping, it is possible to identify genomic regions where allele-frequencies have diverged during selection. To avoid false positive signatures of selection, it is necessary to show that a sweep affects a selected trait before it can be considered adaptive. Here, we confirm candidate, genome-wide distributed selective sweeps originating from the standing genetic variation in a long-term selection experiment on high and low body weight of chickens. Results Using an intercross between the two divergent chicken lines, 16 adaptive selective sweeps were confirmed based on their association with the body weight at 56 days of age. Although individual additive effects were small, the fixation for alternative alleles across the loci contributed at least 40 % of the phenotypic difference for the selected trait between these lines. The sweeps contributed about half of the additive genetic variance present within and between the lines after 40 generations of selection, corresponding to a considerable portion of the additive genetic variance of the base population. Conclusions Long-term, single-trait, bi-directional selection in the Virginia chicken lines has resulted in a gradual response to selection for extreme phenotypes without a drastic reduction in the genetic variation. We find that fixation of several standing genetic variants across a highly polygenic genetic architecture made a considerable contribution to long-term selection response. This provides new fundamental insights into the dynamics of standing genetic variation during long-term selection and adaptation.