A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits

Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematicall...
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Autor*in:	Zhu, Jun [verfasserIn] Chen, Congying Yang, Bin Guo, Yuanmei Ai, Huashui Ren, Jun Peng, Zhiyu Tu, Zhidong Yang, Xia Meng, Qingying Friend, Stephen Huang, Lusheng

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Systems genetics Swine model Complex human traits

Anmerkung:	© Zhu et al.; licensee BioMed Central. 2015

Übergeordnetes Werk:	Enthalten in: BMC genomics - London : BioMed Central, 2000, 16(2015), 1 vom: 14. Feb.
Übergeordnetes Werk:	volume:16 ; year:2015 ; number:1 ; day:14 ; month:02

Links:	Volltext

DOI / URN:	10.1186/s12864-015-1240-y

Katalog-ID:	SPR027102955

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allfields	10.1186/s12864-015-1240-y doi (DE-627)SPR027102955 (SPR)s12864-015-1240-y-e DE-627 ger DE-627 rakwb eng Zhu, Jun verfasserin aut A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhu et al.; licensee BioMed Central. 2015 Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. Results We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process “cellular lipid metabolism” in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number. Conclusion Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection. Systems genetics (dpeaa)DE-He213 Swine model (dpeaa)DE-He213 Complex human traits (dpeaa)DE-He213 Chen, Congying aut Yang, Bin aut Guo, Yuanmei aut Ai, Huashui aut Ren, Jun aut Peng, Zhiyu aut Tu, Zhidong aut Yang, Xia aut Meng, Qingying aut Friend, Stephen aut Huang, Lusheng aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 14. Feb. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:14 month:02 https://dx.doi.org/10.1186/s12864-015-1240-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 14 02
spelling	10.1186/s12864-015-1240-y doi (DE-627)SPR027102955 (SPR)s12864-015-1240-y-e DE-627 ger DE-627 rakwb eng Zhu, Jun verfasserin aut A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhu et al.; licensee BioMed Central. 2015 Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. Results We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process “cellular lipid metabolism” in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number. Conclusion Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection. Systems genetics (dpeaa)DE-He213 Swine model (dpeaa)DE-He213 Complex human traits (dpeaa)DE-He213 Chen, Congying aut Yang, Bin aut Guo, Yuanmei aut Ai, Huashui aut Ren, Jun aut Peng, Zhiyu aut Tu, Zhidong aut Yang, Xia aut Meng, Qingying aut Friend, Stephen aut Huang, Lusheng aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 14. Feb. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:14 month:02 https://dx.doi.org/10.1186/s12864-015-1240-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 14 02
allfields_unstemmed	10.1186/s12864-015-1240-y doi (DE-627)SPR027102955 (SPR)s12864-015-1240-y-e DE-627 ger DE-627 rakwb eng Zhu, Jun verfasserin aut A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhu et al.; licensee BioMed Central. 2015 Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. Results We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process “cellular lipid metabolism” in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number. Conclusion Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection. Systems genetics (dpeaa)DE-He213 Swine model (dpeaa)DE-He213 Complex human traits (dpeaa)DE-He213 Chen, Congying aut Yang, Bin aut Guo, Yuanmei aut Ai, Huashui aut Ren, Jun aut Peng, Zhiyu aut Tu, Zhidong aut Yang, Xia aut Meng, Qingying aut Friend, Stephen aut Huang, Lusheng aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 14. Feb. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:14 month:02 https://dx.doi.org/10.1186/s12864-015-1240-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 14 02
allfieldsGer	10.1186/s12864-015-1240-y doi (DE-627)SPR027102955 (SPR)s12864-015-1240-y-e DE-627 ger DE-627 rakwb eng Zhu, Jun verfasserin aut A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhu et al.; licensee BioMed Central. 2015 Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. Results We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process “cellular lipid metabolism” in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number. Conclusion Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection. Systems genetics (dpeaa)DE-He213 Swine model (dpeaa)DE-He213 Complex human traits (dpeaa)DE-He213 Chen, Congying aut Yang, Bin aut Guo, Yuanmei aut Ai, Huashui aut Ren, Jun aut Peng, Zhiyu aut Tu, Zhidong aut Yang, Xia aut Meng, Qingying aut Friend, Stephen aut Huang, Lusheng aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 14. Feb. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:14 month:02 https://dx.doi.org/10.1186/s12864-015-1240-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 14 02
allfieldsSound	10.1186/s12864-015-1240-y doi (DE-627)SPR027102955 (SPR)s12864-015-1240-y-e DE-627 ger DE-627 rakwb eng Zhu, Jun verfasserin aut A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhu et al.; licensee BioMed Central. 2015 Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. Results We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process “cellular lipid metabolism” in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number. Conclusion Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection. Systems genetics (dpeaa)DE-He213 Swine model (dpeaa)DE-He213 Complex human traits (dpeaa)DE-He213 Chen, Congying aut Yang, Bin aut Guo, Yuanmei aut Ai, Huashui aut Ren, Jun aut Peng, Zhiyu aut Tu, Zhidong aut Yang, Xia aut Meng, Qingying aut Friend, Stephen aut Huang, Lusheng aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 14. Feb. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:14 month:02 https://dx.doi.org/10.1186/s12864-015-1240-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 14 02
language	English
source	Enthalten in BMC genomics 16(2015), 1 vom: 14. Feb. volume:16 year:2015 number:1 day:14 month:02
sourceStr	Enthalten in BMC genomics 16(2015), 1 vom: 14. Feb. volume:16 year:2015 number:1 day:14 month:02
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Systems genetics Swine model Complex human traits
isfreeaccess_bool	true
container_title	BMC genomics
authorswithroles_txt_mv	Zhu, Jun @@aut@@ Chen, Congying @@aut@@ Yang, Bin @@aut@@ Guo, Yuanmei @@aut@@ Ai, Huashui @@aut@@ Ren, Jun @@aut@@ Peng, Zhiyu @@aut@@ Tu, Zhidong @@aut@@ Yang, Xia @@aut@@ Meng, Qingying @@aut@@ Friend, Stephen @@aut@@ Huang, Lusheng @@aut@@
publishDateDaySort_date	2015-02-14T00:00:00Z
hierarchy_top_id	326644954
id	SPR027102955
language_de	englisch
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author	Zhu, Jun
spellingShingle	Zhu, Jun misc Systems genetics misc Swine model misc Complex human traits A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits
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topic_title	A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits Systems genetics (dpeaa)DE-He213 Swine model (dpeaa)DE-He213 Complex human traits (dpeaa)DE-He213
topic	misc Systems genetics misc Swine model misc Complex human traits
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title	A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits
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title_full	A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits
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author_browse	Zhu, Jun Chen, Congying Yang, Bin Guo, Yuanmei Ai, Huashui Ren, Jun Peng, Zhiyu Tu, Zhidong Yang, Xia Meng, Qingying Friend, Stephen Huang, Lusheng
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title_sort	systems genetics study of swine illustrates mechanisms underlying human phenotypic traits
title_auth	A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits
abstract	Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. Results We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process “cellular lipid metabolism” in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number. Conclusion Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection. © Zhu et al.; licensee BioMed Central. 2015
abstractGer	Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. Results We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process “cellular lipid metabolism” in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number. Conclusion Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection. © Zhu et al.; licensee BioMed Central. 2015
abstract_unstemmed	Background The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. Results We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process “cellular lipid metabolism” in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number. Conclusion Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection. © Zhu et al.; licensee BioMed Central. 2015
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title_short	A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits
url	https://dx.doi.org/10.1186/s12864-015-1240-y
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author2	Chen, Congying Yang, Bin Guo, Yuanmei Ai, Huashui Ren, Jun Peng, Zhiyu Tu, Zhidong Yang, Xia Meng, Qingying Friend, Stephen Huang, Lusheng
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A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits

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