--- _id: '11388' abstract: - lang: eng text: "In evolve and resequence experiments, a population is sequenced, subjected to selection and\r\nthen sequenced again, so that genetic changes before and after selection can be observed at\r\nthe genetic level. Here, I use these studies to better understand the genetic basis of complex\r\ntraits - traits which depend on more than a few genes.\r\nIn the first chapter, I discuss the first evolve and resequence experiment, in which a population\r\nof mice, the so-called \"Longshanks\" mice, were selected for tibia length while their body mass\r\nwas kept constant. The full pedigree is known. We observed a selection response on all\r\nchromosomes and used the infinitesimal model with linkage, a model which assumes an infinite\r\nnumber of genes with infinitesimally small effect sizes, as a null model. Results implied a very\r\npolygenic basis with a few loci of major effect standing out and changing in parallel. There\r\nwas large variability between the different chromosomes in this study, probably due to LD.\r\nIn chapter two, I go on to discuss the impact of LD, on the variability in an allele-frequency\r\nbased summary statistic, giving an equation based on the initial allele frequencies, average\r\npairwise LD, and the first four moments of the haplotype block copy number distribution. I\r\ndescribe this distribution by referring back to the founder generation. I then demonstrate\r\nhow to infer selection via a maximum likelihood scheme on the example of a single locus and\r\ndiscuss how to extend this to more realistic scenarios.\r\nIn chapter three, I discuss the second evolve and resequence experiment, in which a small\r\npopulation of Drosophila melanogaster was selected for increased pupal case size over 6\r\ngenerations. The experiment was highly replicated with 27 lines selected within family and a\r\nknown pedigree. We observed a phenotypic selection response of over one standard deviation.\r\nI describe the patterns in allele frequency data, including allele frequency changes and patterns\r\nof heterozygosity, and give ideas for future work." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Stefanie full_name: Belohlavy, Stefanie id: 43FE426A-F248-11E8-B48F-1D18A9856A87 last_name: Belohlavy orcid: 0000-0002-9849-498X citation: ama: Belohlavy S. The genetic basis of complex traits studied via analysis of evolve and resequence experiments. 2022. doi:10.15479/at:ista:11388 apa: Belohlavy, S. (2022). The genetic basis of complex traits studied via analysis of evolve and resequence experiments. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11388 chicago: Belohlavy, Stefanie. “The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11388. ieee: S. Belohlavy, “The genetic basis of complex traits studied via analysis of evolve and resequence experiments,” Institute of Science and Technology Austria, 2022. ista: Belohlavy S. 2022. The genetic basis of complex traits studied via analysis of evolve and resequence experiments. Institute of Science and Technology Austria. mla: Belohlavy, Stefanie. The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11388. short: S. Belohlavy, The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments, Institute of Science and Technology Austria, 2022. date_created: 2022-05-16T16:49:18Z date_published: 2022-05-18T00:00:00Z date_updated: 2023-08-29T06:41:51Z day: '18' ddc: - '576' degree_awarded: PhD department: - _id: GradSch - _id: NiBa doi: 10.15479/at:ista:11388 file: - access_level: open_access checksum: 4d75e6a619df7e8a9d6e840aee182380 content_type: application/pdf creator: sbelohla date_created: 2022-05-19T13:03:13Z date_updated: 2023-05-20T22:30:03Z embargo: 2023-05-19 file_id: '11398' file_name: thesis_sb_final_pdfa.pdf file_size: 8247240 relation: main_file - access_level: closed checksum: 7a5d8b6dd0ca00784f860075b0a7d8f0 content_type: application/x-zip-compressed creator: sbelohla date_created: 2022-05-19T13:07:47Z date_updated: 2023-05-20T22:30:03Z embargo_to: open_access file_id: '11399' file_name: thesis_sb_final.zip file_size: 7094 relation: source_file file_date_updated: 2023-05-20T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '98' publication_identifier: isbn: - 978-3-99078-018-3 publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6713' relation: part_of_dissertation status: public status: public supervisor: - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 title: The genetic basis of complex traits studied via analysis of evolve and resequence experiments tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2022' ... --- _id: '9804' abstract: - lang: eng text: Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response. article_processing_charge: No author: - first_name: João Pl full_name: Castro, João Pl last_name: Castro - first_name: Michelle N. full_name: Yancoskie, Michelle N. last_name: Yancoskie - first_name: Marta full_name: Marchini, Marta last_name: Marchini - first_name: Stefanie full_name: Belohlavy, Stefanie id: 43FE426A-F248-11E8-B48F-1D18A9856A87 last_name: Belohlavy orcid: 0000-0002-9849-498X - first_name: Layla full_name: Hiramatsu, Layla last_name: Hiramatsu - first_name: Marek full_name: Kučka, Marek last_name: Kučka - first_name: William H. full_name: Beluch, William H. last_name: Beluch - first_name: Ronald full_name: Naumann, Ronald last_name: Naumann - first_name: Isabella full_name: Skuplik, Isabella last_name: Skuplik - first_name: John full_name: Cobb, John last_name: Cobb - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Campbell full_name: Rolian, Campbell last_name: Rolian - first_name: Yingguang Frank full_name: Chan, Yingguang Frank last_name: Chan citation: ama: 'Castro JP, Yancoskie MN, Marchini M, et al. Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. 2019. doi:10.5061/dryad.0q2h6tk' apa: 'Castro, J. P., Yancoskie, M. N., Marchini, M., Belohlavy, S., Hiramatsu, L., Kučka, M., … Chan, Y. F. (2019). Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. Dryad. https://doi.org/10.5061/dryad.0q2h6tk' chicago: 'Castro, João Pl, Michelle N. Yancoskie, Marta Marchini, Stefanie Belohlavy, Layla Hiramatsu, Marek Kučka, William H. Beluch, et al. “Data from: An Integrative Genomic Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice.” Dryad, 2019. https://doi.org/10.5061/dryad.0q2h6tk.' ieee: 'J. P. Castro et al., “Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice.” Dryad, 2019.' ista: 'Castro JP, Yancoskie MN, Marchini M, Belohlavy S, Hiramatsu L, Kučka M, Beluch WH, Naumann R, Skuplik I, Cobb J, Barton NH, Rolian C, Chan YF. 2019. Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice, Dryad, 10.5061/dryad.0q2h6tk.' mla: 'Castro, João Pl, et al. Data from: An Integrative Genomic Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice. Dryad, 2019, doi:10.5061/dryad.0q2h6tk.' short: J.P. Castro, M.N. Yancoskie, M. Marchini, S. Belohlavy, L. Hiramatsu, M. Kučka, W.H. Beluch, R. Naumann, I. Skuplik, J. Cobb, N.H. Barton, C. Rolian, Y.F. Chan, (2019). date_created: 2021-08-06T11:52:54Z date_published: 2019-06-06T00:00:00Z date_updated: 2023-08-29T06:41:51Z day: '06' department: - _id: NiBa doi: 10.5061/dryad.0q2h6tk main_file_link: - open_access: '1' url: https://doi.org/10.5061/dryad.0q2h6tk month: '06' oa: 1 oa_version: Published Version publisher: Dryad related_material: record: - id: '6713' relation: used_in_publication status: public status: public title: 'Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice' type: research_data_reference user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf year: '2019' ... --- _id: '6713' abstract: - lang: eng text: Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response. article_number: e42014 article_processing_charge: No author: - first_name: João Pl full_name: Castro, João Pl last_name: Castro - first_name: Michelle N. full_name: Yancoskie, Michelle N. last_name: Yancoskie - first_name: Marta full_name: Marchini, Marta last_name: Marchini - first_name: Stefanie full_name: Belohlavy, Stefanie id: 43FE426A-F248-11E8-B48F-1D18A9856A87 last_name: Belohlavy orcid: 0000-0002-9849-498X - first_name: Layla full_name: Hiramatsu, Layla last_name: Hiramatsu - first_name: Marek full_name: Kučka, Marek last_name: Kučka - first_name: William H. full_name: Beluch, William H. last_name: Beluch - first_name: Ronald full_name: Naumann, Ronald last_name: Naumann - first_name: Isabella full_name: Skuplik, Isabella last_name: Skuplik - first_name: John full_name: Cobb, John last_name: Cobb - first_name: Nicholas H full_name: Barton, Nicholas H id: 4880FE40-F248-11E8-B48F-1D18A9856A87 last_name: Barton orcid: 0000-0002-8548-5240 - first_name: Campbell full_name: Rolian, Campbell last_name: Rolian - first_name: Yingguang Frank full_name: Chan, Yingguang Frank last_name: Chan citation: ama: Castro JP, Yancoskie MN, Marchini M, et al. An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. eLife. 2019;8. doi:10.7554/eLife.42014 apa: Castro, J. P., Yancoskie, M. N., Marchini, M., Belohlavy, S., Hiramatsu, L., Kučka, M., … Chan, Y. F. (2019). An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.42014 chicago: Castro, João Pl, Michelle N. Yancoskie, Marta Marchini, Stefanie Belohlavy, Layla Hiramatsu, Marek Kučka, William H. Beluch, et al. “An Integrative Genomic Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.42014. ieee: J. P. Castro et al., “An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice,” eLife, vol. 8. eLife Sciences Publications, 2019. ista: Castro JP, Yancoskie MN, Marchini M, Belohlavy S, Hiramatsu L, Kučka M, Beluch WH, Naumann R, Skuplik I, Cobb J, Barton NH, Rolian C, Chan YF. 2019. An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice. eLife. 8, e42014. mla: Castro, João Pl, et al. “An Integrative Genomic Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice.” ELife, vol. 8, e42014, eLife Sciences Publications, 2019, doi:10.7554/eLife.42014. short: J.P. Castro, M.N. Yancoskie, M. Marchini, S. Belohlavy, L. Hiramatsu, M. Kučka, W.H. Beluch, R. Naumann, I. Skuplik, J. Cobb, N.H. Barton, C. Rolian, Y.F. Chan, ELife 8 (2019). date_created: 2019-07-28T21:59:17Z date_published: 2019-06-06T00:00:00Z date_updated: 2024-03-28T23:30:23Z day: '06' ddc: - '576' department: - _id: NiBa doi: 10.7554/eLife.42014 external_id: isi: - '000473588700001' pmid: - '31169497' file: - access_level: open_access checksum: fa0936fe58f0d9e3f8e75038570e5a17 content_type: application/pdf creator: apreinsp date_created: 2019-07-29T07:41:18Z date_updated: 2020-07-14T12:47:38Z file_id: '6721' file_name: 2019_eLife_Castro.pdf file_size: 6748249 relation: main_file file_date_updated: 2020-07-14T12:47:38Z has_accepted_license: '1' intvolume: ' 8' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version pmid: 1 publication: eLife publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' related_material: record: - id: '9804' relation: research_data status: public - id: '11388' relation: dissertation_contains status: public scopus_import: '1' status: public title: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 8 year: '2019' ...