[{"date_published":"2022-05-18T00:00:00Z","citation":{"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.","short":"S. Belohlavy, The Genetic Basis of Complex Traits Studied via Analysis of Evolve and Resequence Experiments, Institute of Science and Technology Austria, 2022.","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.","ieee":"S. Belohlavy, “The genetic basis of complex traits studied via analysis of evolve and resequence experiments,” Institute of Science and Technology Austria, 2022.","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","ista":"Belohlavy S. 2022. The genetic basis of complex traits studied via analysis of evolve and resequence experiments. Institute of Science and Technology Austria.","ama":"Belohlavy S. The genetic basis of complex traits studied via analysis of evolve and resequence experiments. 2022. doi:10.15479/at:ista:11388"},"page":"98","day":"18","has_accepted_license":"1","article_processing_charge":"No","file":[{"file_id":"11398","embargo":"2023-05-19","relation":"main_file","date_updated":"2023-05-20T22:30:03Z","date_created":"2022-05-19T13:03:13Z","checksum":"4d75e6a619df7e8a9d6e840aee182380","file_name":"thesis_sb_final_pdfa.pdf","access_level":"open_access","creator":"sbelohla","content_type":"application/pdf","file_size":8247240},{"access_level":"closed","file_name":"thesis_sb_final.zip","embargo_to":"open_access","creator":"sbelohla","content_type":"application/x-zip-compressed","file_size":7094,"file_id":"11399","relation":"source_file","checksum":"7a5d8b6dd0ca00784f860075b0a7d8f0","date_created":"2022-05-19T13:07:47Z","date_updated":"2023-05-20T22:30:03Z"}],"oa_version":"Published Version","_id":"11388","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","ddc":["576"],"status":"public","title":"The genetic basis of complex traits studied via analysis of evolve and resequence experiments","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."}],"type":"dissertation","alternative_title":["ISTA Thesis"],"doi":"10.15479/at:ista:11388","degree_awarded":"PhD","supervisor":[{"last_name":"Barton","first_name":"Nicholas H","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H"}],"language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"month":"05","publication_identifier":{"isbn":["978-3-99078-018-3"]},"author":[{"full_name":"Belohlavy, Stefanie","first_name":"Stefanie","last_name":"Belohlavy","id":"43FE426A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9849-498X"}],"related_material":{"record":[{"id":"6713","relation":"part_of_dissertation","status":"public"}]},"date_created":"2022-05-16T16:49:18Z","date_updated":"2023-08-29T06:41:51Z","year":"2022","publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"NiBa"}],"file_date_updated":"2023-05-20T22:30:03Z"},{"article_processing_charge":"No","month":"06","day":"06","date_published":"2019-06-06T00:00:00Z","doi":"10.5061/dryad.0q2h6tk","oa":1,"citation":{"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.","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).","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.","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","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.","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"},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.0q2h6tk"}],"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."}],"type":"research_data_reference","oa_version":"Published Version","date_updated":"2023-08-29T06:41:51Z","date_created":"2021-08-06T11:52:54Z","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"6713"}]},"author":[{"full_name":"Castro, João Pl","first_name":"João Pl","last_name":"Castro"},{"first_name":"Michelle N.","last_name":"Yancoskie","full_name":"Yancoskie, Michelle N."},{"full_name":"Marchini, Marta","last_name":"Marchini","first_name":"Marta"},{"first_name":"Stefanie","last_name":"Belohlavy","id":"43FE426A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9849-498X","full_name":"Belohlavy, Stefanie"},{"full_name":"Hiramatsu, Layla","first_name":"Layla","last_name":"Hiramatsu"},{"full_name":"Kučka, Marek","first_name":"Marek","last_name":"Kučka"},{"full_name":"Beluch, William H.","first_name":"William H.","last_name":"Beluch"},{"full_name":"Naumann, Ronald","last_name":"Naumann","first_name":"Ronald"},{"first_name":"Isabella","last_name":"Skuplik","full_name":"Skuplik, Isabella"},{"last_name":"Cobb","first_name":"John","full_name":"Cobb, John"},{"full_name":"Barton, Nicholas H","first_name":"Nicholas H","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240"},{"last_name":"Rolian","first_name":"Campbell","full_name":"Rolian, Campbell"},{"full_name":"Chan, Yingguang Frank","first_name":"Yingguang Frank","last_name":"Chan"}],"department":[{"_id":"NiBa"}],"publisher":"Dryad","status":"public","title":"Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice","_id":"9804","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","year":"2019"},{"month":"06","language":[{"iso":"eng"}],"doi":"10.7554/eLife.42014","isi":1,"quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["31169497"],"isi":["000473588700001"]},"file_date_updated":"2020-07-14T12:47:38Z","article_number":"e42014","date_created":"2019-07-28T21:59:17Z","date_updated":"2024-03-28T23:30:23Z","volume":8,"author":[{"last_name":"Castro","first_name":"João Pl","full_name":"Castro, João Pl"},{"full_name":"Yancoskie, Michelle N.","last_name":"Yancoskie","first_name":"Michelle N."},{"full_name":"Marchini, Marta","first_name":"Marta","last_name":"Marchini"},{"full_name":"Belohlavy, Stefanie","id":"43FE426A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9849-498X","first_name":"Stefanie","last_name":"Belohlavy"},{"first_name":"Layla","last_name":"Hiramatsu","full_name":"Hiramatsu, Layla"},{"full_name":"Kučka, Marek","last_name":"Kučka","first_name":"Marek"},{"first_name":"William H.","last_name":"Beluch","full_name":"Beluch, William H."},{"full_name":"Naumann, Ronald","last_name":"Naumann","first_name":"Ronald"},{"first_name":"Isabella","last_name":"Skuplik","full_name":"Skuplik, Isabella"},{"full_name":"Cobb, John","first_name":"John","last_name":"Cobb"},{"first_name":"Nicholas H","last_name":"Barton","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H"},{"last_name":"Rolian","first_name":"Campbell","full_name":"Rolian, Campbell"},{"full_name":"Chan, Yingguang Frank","first_name":"Yingguang Frank","last_name":"Chan"}],"related_material":{"record":[{"id":"9804","relation":"research_data","status":"public"},{"id":"11388","status":"public","relation":"dissertation_contains"}]},"publication_status":"published","department":[{"_id":"NiBa"}],"publisher":"eLife Sciences Publications","year":"2019","pmid":1,"day":"06","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","date_published":"2019-06-06T00:00:00Z","publication":"eLife","citation":{"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).","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.","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","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.","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","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."},"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."}],"type":"journal_article","oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:47:38Z","date_created":"2019-07-29T07:41:18Z","checksum":"fa0936fe58f0d9e3f8e75038570e5a17","file_id":"6721","relation":"main_file","creator":"apreinsp","file_size":6748249,"content_type":"application/pdf","file_name":"2019_eLife_Castro.pdf","access_level":"open_access"}],"ddc":["576"],"status":"public","title":"An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice","intvolume":" 8","_id":"6713","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"}]