uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 108) Show all publications
Guo, Y., Lillie, M., Zan, Y., Beranger, J., Martin, A., Honaker, C., . . . Carlborg, Ö. (2019). A genomic inference of the White Plymouth Rock genealogy. Poultry Science
Open this publication in new window or tab >>A genomic inference of the White Plymouth Rock genealogy
Show others...
2019 (English)In: Poultry Science, ISSN 0032-5791, E-ISSN 1525-3171Article in journal (Refereed) Epub ahead of print
Abstract [en]

Crossing of populations has been, and still is, a central component in domestication and breed and variety formation. It is a way for breeders to utilize heterosis and to introduce new genetic variation into existing plant and livestock populations. During the mid-19thcentury, several chicken breeds that had been introduced to America from Europe and Asia became the founders for those formed in the USA. Historical records about the genealogy of these populations are often unclear and inconsistent. Here, we used genomics in an attempt to describe the ancestry of the White Plymouth Rock (WPR) chicken. In total, 150 chickens from the WPR and 8 other stocks that historical records suggested contributed to its formation were whole-genome re-sequenced. The admixture analyses of the autosomal and sex chromosomes showed that the WPR was likely founded as a cross between a paternal lineage that was primarily Dominique, and a maternal lineage where Black Java and Cochin contributed in equal proportions. These results were consistent and provided quantification with the historical records that they were the main contributors to the WPR. The genomic analyses also revealed genome-wide contributions (<10% each) by Brahma, Langshan, and Black Minorca. When viewed on an individual chromosomal basis, contributions varied considerably among stocks. 

Keywords
Domestication, Ancestry, Admixture, Phenotype-genotype interface, Chickens
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-388828 (URN)10.3382/ps/pez411 (DOI)
Available from: 2019-07-05 Created: 2019-07-05 Last updated: 2019-08-16Bibliographically approved
Zan, Y. & Carlborg, Ö. (2019). A polygenic genetic architecture of flowering time in the worldwide Arabidopsis thaliana population.. Molecular biology and evolution, 36(1), 141-154
Open this publication in new window or tab >>A polygenic genetic architecture of flowering time in the worldwide Arabidopsis thaliana population.
2019 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 36, no 1, p. 141-154Article in journal (Refereed) Published
Abstract [en]

Here, we report an empirical study of the polygenic basis underlying the evolution of complex traits. Flowering time variation measured at 10 and 16 °C in the 1,001-genomes Arabidopsis thaliana collection of natural accessions were used as a model. The polygenic architecture of flowering time was defined as the 48 loci that were significantly associated with flowering time - at 10 and/or 16 °C and/or their difference - in this population. Contributions from alleles at flowering time associated loci to global and local adaptation were explored by evaluating their distribution across genetically and geographically defined subpopulations across the native range of the species. The dynamics in the genetic architecture of flowering time in response to temperature was evaluated by estimating how the effects of these loci on flowering changed with growth temperature. Overall, the genetic basis of flowering time was stable - about 2/3 of the flowering time loci had similar effects at 10 °C and 16 °C - but many loci were involved in gene by temperature interactions. Globally present alleles, mostly of moderate effect, contributed to the differences in flowering times between the subpopulations via subtle changes in allele-frequencies. More extreme local adaptations were, on several occasions, due to regional alleles with relatively large effects, and their LD-patterns suggest co-evolution of functionally connected alleles within local populations. Overall, these findings provide a significant contribution to our understanding about the possible modes of global and local evolution of a complex adaptive trait in Arabidopsis thaliana.

National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-364954 (URN)10.1093/molbev/msy203 (DOI)000459327400012 ()30388255 (PubMedID)
Available from: 2018-11-07 Created: 2018-11-07 Last updated: 2019-08-01Bibliographically approved
Lillie, M., Honaker, C. F., Siegel, P. B. & Carlborg, Ö. (2019). Bidirectional Selection for Body Weight on Standing Genetic Variation in a Chicken Model. G3: Genes, Genomes, Genetics, 9(4), 1165-1173
Open this publication in new window or tab >>Bidirectional Selection for Body Weight on Standing Genetic Variation in a Chicken Model
2019 (English)In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 9, no 4, p. 1165-1173Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Chicken, White Plymouth Rock, selective sweeps, body weight, quantitative trait
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-382651 (URN)10.1534/g3.119.400038 (DOI)000463929500018 ()30737239 (PubMedID)
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationSwedish National Infrastructure for Computing (SNIC), b2015010Swedish Research Council Formas, DNR 221-2013-450
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-04-29Bibliographically approved
Zan, Y., Forsberg, S. K. G. & Carlborg, Ö. (2018). On the Relationship Between High-Order Linkage Disequilibrium and Epistasis. G3: Genes, Genomes, Genetics, 8(8), 2817-2824
Open this publication in new window or tab >>On the Relationship Between High-Order Linkage Disequilibrium and Epistasis
2018 (English)In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 8, no 8, p. 2817-2824Article in journal (Refereed) Published
Abstract [en]

A plausible explanation for statistical epistasis revealed in genome wide association analyses is the presence of high order linkage disequilibrium (LD) between the genotyped markers tested for interactions and unobserved functional polymorphisms. Based on findings in experimental data, it has been suggested that high order LD might be a common explanation for statistical epistasis inferred between local polymorphisms in the same genomic region. Here, we empirically evaluate how prevalent high order LD is between local, as well as distal, polymorphisms in the genome. This could provide insights into whether we should account for this when interpreting results from genome wide scans for statistical epistasis. An extensive and strong genome wide high order LD was revealed between pairs of markers on the high density 250k SNP-chip and individual markers revealed by whole genome sequencing in the Arabidopsis thaliana 1001-genomes collection. The high order LD was found to be more prevalent in smaller populations, but present also in samples including several hundred individuals. An empirical example illustrates that high order LD might be an even greater challenge in cases when the genetic architecture is more complex than the common assumption of bi-allelic loci. The example shows how significant statistical epistasis is detected for a pair of markers in high order LD with a complex multi allelic locus. Overall, our study illustrates the importance of considering also other explanations than functional genetic interactions when genome wide statistical epistasis is detected, in particular when the results are obtained in small populations of inbred individuals.

Place, publisher, year, edition, pages
GENETICS SOCIETY AMERICA, 2018
Keywords
Arabidopsis thaliana, epistasis, high order linkage disequilibrium, leaf, molybdenum
National Category
Genetics
Research subject
Biology
Identifiers
urn:nbn:se:uu:diva-356530 (URN)10.1534/g3.118.200513 (DOI)000440327400025 ()29945968 (PubMedID)
Funder
Swedish Research Council Formas, 2013-450Swedish Research Council, 2012-4634
Available from: 2018-07-31 Created: 2018-07-31 Last updated: 2018-11-12Bibliographically approved
Forsberg, S. K. G., Bloom, J. S., Sadhu, M. J., Kruglyak, L. & Carlborg, Ö. (2017). Accounting for genetic interactions improves modeling of individual quantitative trait phenotypes in yeast. Nature Genetics, 49(4), 497-503
Open this publication in new window or tab >>Accounting for genetic interactions improves modeling of individual quantitative trait phenotypes in yeast
Show others...
2017 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, no 4, p. 497-503Article in journal (Refereed) Published
Abstract [en]

Experiments in model organisms report abundant genetic interactions underlying biologically important traits, whereas quantitative genetics theory predicts, and data support, the notion that most genetic variance in populations is additive. Here we describe networks of capacitating genetic interactions that contribute to quantitative trait variation in a large yeast intercross population. The additive variance explained by individual loci in a network is highly dependent on the allele frequencies of the interacting loci. Modeling of phenotypes for multilocus genotype classes in the epistatic networks is often improved by accounting for the interactions. We discuss the implications of these results for attempts to dissect genetic architectures and to predict individual phenotypes and long-term responses to selection.

National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-316620 (URN)10.1038/ng.3800 (DOI)000397603700012 ()28250458 (PubMedID)
Funder
NIH (National Institute of Health), R01 GM102308 F32 GM116318Swedish Research Council, 621-2012-4632
Available from: 2017-03-06 Created: 2017-03-06 Last updated: 2018-01-18
Zan, Y., Sheng, Z., Lillie, M., Rönnegård, L., Honaker, C. F., Siegel, P. B. & Carlborg, Ö. (2017). Artificial Selection Response due to Polygenic Adaptation from a Multilocus, Multiallelic Genetic Architecture.. Molecular biology and evolution, 34(10), 2678-2689
Open this publication in new window or tab >>Artificial Selection Response due to Polygenic Adaptation from a Multilocus, Multiallelic Genetic Architecture.
Show others...
2017 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 34, no 10, p. 2678-2689Article in journal (Refereed) Published
Abstract [en]

The ability of a population to adapt to changes in their living conditions, whether in nature or captivity, often depends on polymorphisms in multiple genes across the genome. In-depth studies of such polygenic adaptations are difficult in natural populations, but can be approached using the resources provided by artificial selection experiments. Here, we dissect the genetic mechanisms involved in long-term selection responses of the Virginia chicken lines, populations that after 40 generations of divergent selection for 56-day body weight display a 9-fold difference in the selected trait. In the F15 generation of an intercross between the divergent lines, 20 loci explained >60% of the additive genetic variance for the selected trait. We focused particularly on fine-mapping seven major QTL that replicated in this population and found that only two fine-mapped to single, bi-allelic loci; the other five contained linked loci, multiple alleles or were epistatic. This detailed dissection of the polygenic adaptations in the Virginia lines provides a deeper understanding of the range of different genome-wide mechanisms that have been involved in these long-term selection responses. The results illustrate that the genetic architecture of a highly polygenic trait can involve a broad range of genetic mechanisms, and that this can be the case even in a small population bred from founders with limited genetic diversity.

Keywords
epistasis, genetic architecture, genetic variation, multiallelic, multilocus, polygenic adaptation
National Category
Natural Sciences Genetics
Identifiers
urn:nbn:se:uu:diva-332731 (URN)10.1093/molbev/msx194 (DOI)000411814800019 ()28957504 (PubMedID)
Funder
Swedish Research Council, 2012-4634Swedish Research Council Formas, 2010-643, 2013-450
Available from: 2017-11-01 Created: 2017-11-01 Last updated: 2018-02-26
Nelson, R. M., Temnykh, S. V., Johnson, J. L., Kharlamova, A. V., Vladimirova, A. V., Gulevich, R. G., . . . Kukekova, A. V. (2017). Genetics of Interactive Behavior in Silver Foxes (Vulpes vulpes). Behavior Genetics, 47(1), 88-101
Open this publication in new window or tab >>Genetics of Interactive Behavior in Silver Foxes (Vulpes vulpes)
Show others...
2017 (English)In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 47, no 1, p. 88-101Article in journal (Refereed) Published
Abstract [en]

Individuals involved in a social interaction exhibit different behavioral traits that, in combination, form the individual's behavioral responses. Selectively bred strains of silver foxes (Vulpes vulpes) demonstrate markedly different behaviors in their response to humans. To identify the genetic basis of these behavioral differences we constructed a large F2 population including 537 individuals by cross-breeding tame and aggressive fox strains. 98 fox behavioral traits were recorded during social interaction with a human experimenter in a standard four-step test. Patterns of fox behaviors during the test were evaluated using principal component (PC) analysis. Genetic mapping identified eight unique significant and suggestive QTL. Mapping results for the PC phenotypes from different test steps showed little overlap suggesting that different QTL are involved in regulation of behaviors exhibited in different behavioral contexts. Many individual behavioral traits mapped to the same genomic regions as PC phenotypes. This provides additional information about specific behaviors regulated by these loci. Further, three pairs of epistatic loci were also identified for PC phenotypes suggesting more complex genetic architecture of the behavioral differences between the two strains than what has previously been observed.

National Category
Zoology
Research subject
Genetics; Bioinformatics
Identifiers
urn:nbn:se:uu:diva-313200 (URN)10.1007/s10519-016-9815-1 (DOI)000392185800008 ()27757730 (PubMedID)
Funder
NIH (National Institute of Health), MH077811
Available from: 2017-01-17 Created: 2017-01-17 Last updated: 2018-01-18
Lillie, M., Sheng, Z., Honaker, C. F., Dorshorst, B. J., Ashwell, C. M., Siegel, P. B. & Carlborg, Ö. (2017). Genome-wide standing variation facilitates long-term response to bidirectional selection for antibody response in chickens. BMC Genomics, 18, Article ID 99.
Open this publication in new window or tab >>Genome-wide standing variation facilitates long-term response to bidirectional selection for antibody response in chickens
Show others...
2017 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 18, article id 99Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Pooled genome sequencing, Selective sweeps, Virginia chicken lines, Sheep red blood cells, Antibody response
National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:uu:diva-313897 (URN)10.1186/s12864-016-3414-7 (DOI)000394380200006 ()28100171 (PubMedID)
Available from: 2017-01-25 Created: 2017-01-25 Last updated: 2018-01-18Bibliographically approved
Lillie, M., Sheng, Z., Honaker, C., Andersson, L., Siegel, P. & Carlborg, Ö. (2017). Genomic signatures of 60 years of bidirectional selection for 8-week body weight in chickens. Poultry Science, 97(3), 781-790
Open this publication in new window or tab >>Genomic signatures of 60 years of bidirectional selection for 8-week body weight in chickens
Show others...
2017 (English)In: Poultry Science, ISSN 0032-5791, E-ISSN 1525-3171, Vol. 97, no 3, p. 781-790Article in journal (Refereed) Published
Abstract [en]

Sixty years, constituting 60 generations, have passed since the founding of the Virginia body weight lines, an experimental population of White Plymouth Rock chickens. Using a stringent breeding scheme for divergent 8-week body weight, the lines, which originated from a common founder population, have responded to bidirectional selection with an approximate 15-fold difference in the selected trait. They provide a model system to study the genetics of complex traits in general and the influences of artificial selection on quantitative genetic architectures in particular. As we reflect on the 60th anniversary of the initiation of the Virginia body weight lines, there is opportunity to discuss the findings obtained using different analytical and experimental genetic and genomic strategies and integrate them with a recent pooled genome resequencing dataset. Hundreds of regions across the genome show differentiation between the 2 lines, reinforcing previous findings that response to selection relied on standing variation across many genes and giving insights into the haplotype complexity underlying regions associated with body weight.

National Category
Genetics Bioinformatics (Computational Biology) Agricultural Science
Research subject
Genetics
Identifiers
urn:nbn:se:uu:diva-337971 (URN)10.3382/ps/pex383 (DOI)000426061600008 ()
Funder
Swedish National Infrastructure for Computing (SNIC), b2015010Swedish Research Council, 2012-4634Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, 2010-643Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, 2013-450
Available from: 2018-01-06 Created: 2018-01-06 Last updated: 2019-06-27Bibliographically approved
Brandt, M., Ahsan, M., Honaker, C. F., Siegel, P. B. & Carlborg, Ö. (2017). Imputation-Based Fine-Mapping Suggests That Most QTL in an Outbred Chicken Advanced Intercross Body Weight Line Are Due to Multiple, Linked Loci. G3: Genes, Genomes, Genetics, 7(1), 119-128
Open this publication in new window or tab >>Imputation-Based Fine-Mapping Suggests That Most QTL in an Outbred Chicken Advanced Intercross Body Weight Line Are Due to Multiple, Linked Loci
Show others...
2017 (English)In: G3: Genes, Genomes, Genetics, ISSN 2160-1836, E-ISSN 2160-1836, Vol. 7, no 1, p. 119-128Article in journal (Refereed) Published
Abstract [en]

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 F2-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.

National Category
Medical Genetics
Research subject
Bioinformatics; Genetics
Identifiers
urn:nbn:se:uu:diva-313199 (URN)10.1534/g3.116.036012 (DOI)000392200800011 ()27799342 (PubMedID)
Funder
Swedish Research Council Formas, 221-2013-450Swedish Research Council, 621-2012-4634
Available from: 2017-01-17 Created: 2017-01-17 Last updated: 2018-01-18Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2722-5264

Search in DiVA

Show all publications