Ruifei Yang1, Xiaoli Guo1, Di Zhu1, Cheng Tan2, Cheng Bian1, Jiangli Ren1, Zhuolin Huang1, Yiqiang Zhao1, Gengyuan Cai2, Dewu Liu2, Zhenfang Wu2, Yuzhe Wang1,3, Ning Li1, Xiaoxiang Hu1. 1. State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan west road, Haidian district, Beijing 100193, China. 2. National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, No. 483 Wushan road, Tianhe district, Guangdong 510640, China. 3. National Research Facility for Phenotypic and Genotypic Analysis of Model Animals (Beijing), China Agricultural University, No. 2 Yuanmingyuan west road, Haidian district, Beijing 100193, China.
Abstract
BACKGROUND: Uncovering the genetic architecture of economic traits in pigs is important for agricultural breeding. However, high-density haplotype reference panels are unavailable in most agricultural species, limiting accurate genotype imputation in large populations. Moreover, the infinitesimal model of quantitative traits implies that weak association signals tend to be spread across most of the genome, further complicating the genetic analysis. Hence, there is a need to develop new methods for sequencing large cohorts without large reference panels. RESULTS: We describe a Tn5-based highly accurate, cost- and time-efficient, low-coverage sequencing method to obtain 11.3 million whole-genome single-nucleotide polymorphisms in 2,869 Duroc boars at a mean depth of 0.73×. On the basis of these single-nucleotide polymorphisms, a genome-wide association study was performed, resulting in 14 quantitative trait loci (QTLs) for 7 of 21 important agricultural traits in pigs. These QTLs harbour genes, such as ABCD4 for total teat number and HMGA1 for back fat thickness, and provided a starting point for further investigation. The inheritance models of the different traits varied greatly. Most follow the minor-polygene model, but this can be attributed to different reasons, such as the shaping of genetic architecture by artificial selection for this population and sufficiently interconnected minor gene regulatory networks. CONCLUSIONS: Genome-wide association study results for 21 important agricultural traits identified 14 QTLs/genes and showed their genetic architectures, providing guidance for genetic improvement harnessing genomic features. The Tn5-based low-coverage sequencing method can be applied to large-scale genome studies for any species without a good reference panel and can be used for agricultural breeding.
BACKGROUND: Uncovering the genetic architecture of economic traits in pigs is important for agricultural breeding. However, high-density haplotype reference panels are unavailable in most agricultural species, limiting accurate genotype imputation in large populations. Moreover, the infinitesimal model of quantitative traits implies that weak association signals tend to be spread across most of the genome, further complicating the genetic analysis. Hence, there is a need to develop new methods for sequencing large cohorts without large reference panels. RESULTS: We describe a Tn5-based highly accurate, cost- and time-efficient, low-coverage sequencing method to obtain 11.3 million whole-genome single-nucleotide polymorphisms in 2,869 Duroc boars at a mean depth of 0.73×. On the basis of these single-nucleotide polymorphisms, a genome-wide association study was performed, resulting in 14 quantitative trait loci (QTLs) for 7 of 21 important agricultural traits in pigs. These QTLs harbour genes, such as ABCD4 for total teat number and HMGA1 for back fat thickness, and provided a starting point for further investigation. The inheritance models of the different traits varied greatly. Most follow the minor-polygene model, but this can be attributed to different reasons, such as the shaping of genetic architecture by artificial selection for this population and sufficiently interconnected minor gene regulatory networks. CONCLUSIONS: Genome-wide association study results for 21 important agricultural traits identified 14 QTLs/genes and showed their genetic architectures, providing guidance for genetic improvement harnessing genomic features. The Tn5-based low-coverage sequencing method can be applied to large-scale genome studies for any species without a good reference panel and can be used for agricultural breeding.
Authors: Hana Lango Allen; Karol Estrada; Guillaume Lettre; Sonja I Berndt; Michael N Weedon; Fernando Rivadeneira; Cristen J Willer; Anne U Jackson; Sailaja Vedantam; Soumya Raychaudhuri; Teresa Ferreira; Andrew R Wood; Robert J Weyant; Ayellet V Segrè; Elizabeth K Speliotes; Eleanor Wheeler; Nicole Soranzo; Ju-Hyun Park; Jian Yang; Daniel Gudbjartsson; Nancy L Heard-Costa; Joshua C Randall; Lu Qi; Albert Vernon Smith; Reedik Mägi; Tomi Pastinen; Liming Liang; Iris M Heid; Jian'an Luan; Gudmar Thorleifsson; Thomas W Winkler; Michael E Goddard; Ken Sin Lo; Cameron Palmer; Tsegaselassie Workalemahu; Yurii S Aulchenko; Asa Johansson; M Carola Zillikens; Mary F Feitosa; Tõnu Esko; Toby Johnson; Shamika Ketkar; Peter Kraft; Massimo Mangino; Inga Prokopenko; Devin Absher; Eva Albrecht; Florian Ernst; Nicole L Glazer; Caroline Hayward; Jouke-Jan Hottenga; Kevin B Jacobs; Joshua W Knowles; Zoltán Kutalik; Keri L Monda; Ozren Polasek; Michael Preuss; Nigel W Rayner; Neil R Robertson; Valgerdur Steinthorsdottir; Jonathan P Tyrer; Benjamin F Voight; Fredrik Wiklund; Jianfeng Xu; Jing Hua Zhao; Dale R Nyholt; Niina Pellikka; Markus Perola; John R B Perry; Ida Surakka; Mari-Liis Tammesoo; Elizabeth L Altmaier; Najaf Amin; Thor Aspelund; Tushar Bhangale; Gabrielle Boucher; Daniel I Chasman; Constance Chen; Lachlan Coin; Matthew N Cooper; Anna L Dixon; Quince Gibson; Elin Grundberg; Ke Hao; M Juhani Junttila; Lee M Kaplan; Johannes Kettunen; Inke R König; Tony Kwan; Robert W Lawrence; Douglas F Levinson; Mattias Lorentzon; Barbara McKnight; Andrew P Morris; Martina Müller; Julius Suh Ngwa; Shaun Purcell; Suzanne Rafelt; Rany M Salem; Erika Salvi; Serena Sanna; Jianxin Shi; Ulla Sovio; John R Thompson; Michael C Turchin; Liesbeth Vandenput; Dominique J Verlaan; Veronique Vitart; Charles C White; Andreas Ziegler; Peter Almgren; Anthony J Balmforth; Harry Campbell; Lorena Citterio; Alessandro De Grandi; Anna Dominiczak; Jubao Duan; Paul Elliott; Roberto Elosua; Johan G Eriksson; Nelson B Freimer; Eco J C Geus; Nicola Glorioso; Shen Haiqing; Anna-Liisa Hartikainen; Aki S Havulinna; Andrew A Hicks; Jennie Hui; Wilmar Igl; Thomas Illig; Antti Jula; Eero Kajantie; Tuomas O Kilpeläinen; Markku Koiranen; Ivana Kolcic; Seppo Koskinen; Peter Kovacs; Jaana Laitinen; Jianjun Liu; Marja-Liisa Lokki; Ana Marusic; Andrea Maschio; Thomas Meitinger; Antonella Mulas; Guillaume Paré; Alex N Parker; John F Peden; Astrid Petersmann; Irene Pichler; Kirsi H Pietiläinen; Anneli Pouta; Martin Ridderstråle; Jerome I Rotter; Jennifer G Sambrook; Alan R Sanders; Carsten Oliver Schmidt; Juha Sinisalo; Jan H Smit; Heather M Stringham; G Bragi Walters; Elisabeth Widen; Sarah H Wild; Gonneke Willemsen; Laura Zagato; Lina Zgaga; Paavo Zitting; Helene Alavere; Martin Farrall; Wendy L McArdle; Mari Nelis; Marjolein J Peters; Samuli Ripatti; Joyce B J van Meurs; Katja K Aben; Kristin G Ardlie; Jacques S Beckmann; John P Beilby; Richard N Bergman; Sven Bergmann; Francis S Collins; Daniele Cusi; Martin den Heijer; Gudny Eiriksdottir; Pablo V Gejman; Alistair S Hall; Anders Hamsten; Heikki V Huikuri; Carlos Iribarren; Mika Kähönen; Jaakko Kaprio; Sekar Kathiresan; Lambertus Kiemeney; Thomas Kocher; Lenore J Launer; Terho Lehtimäki; Olle Melander; Tom H Mosley; Arthur W Musk; Markku S Nieminen; Christopher J O'Donnell; Claes Ohlsson; Ben Oostra; Lyle J Palmer; Olli Raitakari; Paul M Ridker; John D Rioux; Aila Rissanen; Carlo Rivolta; Heribert Schunkert; Alan R Shuldiner; David S Siscovick; Michael Stumvoll; Anke Tönjes; Jaakko Tuomilehto; Gert-Jan van Ommen; Jorma Viikari; Andrew C Heath; Nicholas G Martin; Grant W Montgomery; Michael A Province; Manfred Kayser; Alice M Arnold; Larry D Atwood; Eric Boerwinkle; Stephen J Chanock; Panos Deloukas; Christian Gieger; Henrik Grönberg; Per Hall; Andrew T Hattersley; Christian Hengstenberg; Wolfgang Hoffman; G Mark Lathrop; Veikko Salomaa; Stefan Schreiber; Manuela Uda; Dawn Waterworth; Alan F Wright; Themistocles L Assimes; Inês Barroso; Albert Hofman; Karen L Mohlke; Dorret I Boomsma; Mark J Caulfield; L Adrienne Cupples; Jeanette Erdmann; Caroline S Fox; Vilmundur Gudnason; Ulf Gyllensten; Tamara B Harris; Richard B Hayes; Marjo-Riitta Jarvelin; Vincent Mooser; Patricia B Munroe; Willem H Ouwehand; Brenda W Penninx; Peter P Pramstaller; Thomas Quertermous; Igor Rudan; Nilesh J Samani; Timothy D Spector; Henry Völzke; Hugh Watkins; James F Wilson; Leif C Groop; Talin Haritunians; Frank B Hu; Robert C Kaplan; Andres Metspalu; Kari E North; David Schlessinger; Nicholas J Wareham; David J Hunter; Jeffrey R O'Connell; David P Strachan; H-Erich Wichmann; Ingrid B Borecki; Cornelia M van Duijn; Eric E Schadt; Unnur Thorsteinsdottir; Leena Peltonen; André G Uitterlinden; Peter M Visscher; Nilanjan Chatterjee; Ruth J F Loos; Michael Boehnke; Mark I McCarthy; Erik Ingelsson; Cecilia M Lindgren; Gonçalo R Abecasis; Kari Stefansson; Timothy M Frayling; Joel N Hirschhorn Journal: Nature Date: 2010-09-29 Impact factor: 49.962
Authors: Yogesh Paudel; Ole Madsen; Hendrik-Jan Megens; Laurent A F Frantz; Mirte Bosse; Richard P M A Crooijmans; Martien A M Groenen Journal: BMC Genomics Date: 2015-04-22 Impact factor: 3.969
Authors: Jérôme Nicod; Robert W Davies; Na Cai; Carl Hassett; Leo Goodstadt; Cormac Cosgrove; Benjamin K Yee; Vikte Lionikaite; Rebecca E McIntyre; Carol Ann Remme; Elisabeth M Lodder; Jennifer S Gregory; Tertius Hough; Russell Joynson; Hayley Phelps; Barbara Nell; Clare Rowe; Joe Wood; Alison Walling; Nasrin Bopp; Amarjit Bhomra; Polinka Hernandez-Pliego; Jacques Callebert; Richard M Aspden; Nick P Talbot; Peter A Robbins; Mark Harrison; Martin Fray; Jean-Marie Launay; Yigal M Pinto; David A Blizard; Connie R Bezzina; David J Adams; Paul Franken; Tom Weaver; Sara Wells; Steve D M Brown; Paul K Potter; Paul Klenerman; Arimantas Lionikas; Richard Mott; Jonathan Flint Journal: Nat Genet Date: 2016-07-04 Impact factor: 38.330
Authors: Roger Ros-Freixedes; Martin Johnsson; Andrew Whalen; Ching-Yi Chen; Bruno D Valente; William O Herring; Gregor Gorjanc; John M Hickey Journal: Genet Sel Evol Date: 2022-09-24 Impact factor: 5.100