Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues
Abstract Background Mammalian phenotypes are shaped by numerous genome variants, many of which may regulate gene transcription or RNA splicing. To identify variants with regulatory functions in cattle, an important economic and model species, we used sequence variants to map a type of expression qua...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-018-4902-8 |
| _version_ | 1819050702657290240 |
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| author | Ruidong Xiang Ben J. Hayes Christy J. Vander Jagt Iona M. MacLeod Majid Khansefid Phil J. Bowman Zehu Yuan Claire P. Prowse-Wilkins Coralie M. Reich Brett A. Mason Josie B. Garner Leah C. Marett Yizhou Chen Sunduimijid Bolormaa Hans D. Daetwyler Amanda J. Chamberlain Michael E. Goddard |
| author_facet | Ruidong Xiang Ben J. Hayes Christy J. Vander Jagt Iona M. MacLeod Majid Khansefid Phil J. Bowman Zehu Yuan Claire P. Prowse-Wilkins Coralie M. Reich Brett A. Mason Josie B. Garner Leah C. Marett Yizhou Chen Sunduimijid Bolormaa Hans D. Daetwyler Amanda J. Chamberlain Michael E. Goddard |
| author_sort | Ruidong Xiang |
| collection | DOAJ |
| description | Abstract Background Mammalian phenotypes are shaped by numerous genome variants, many of which may regulate gene transcription or RNA splicing. To identify variants with regulatory functions in cattle, an important economic and model species, we used sequence variants to map a type of expression quantitative trait loci (expression QTLs) that are associated with variations in the RNA splicing, i.e., sQTLs. To further the understanding of regulatory variants, sQTLs were compare with other two types of expression QTLs, 1) variants associated with variations in gene expression, i.e., geQTLs and 2) variants associated with variations in exon expression, i.e., eeQTLs, in different tissues. Results Using whole genome and RNA sequence data from four tissues of over 200 cattle, sQTLs identified using exon inclusion ratios were verified by matching their effects on adjacent intron excision ratios. sQTLs contained the highest percentage of variants that are within the intronic region of genes and contained the lowest percentage of variants that are within intergenic regions, compared to eeQTLs and geQTLs. Many geQTLs and sQTLs are also detected as eeQTLs. Many expression QTLs, including sQTLs, were significant in all four tissues and had a similar effect in each tissue. To verify such expression QTL sharing between tissues, variants surrounding (±1 Mb) the exon or gene were used to build local genomic relationship matrices (LGRM) and estimated genetic correlations between tissues. For many exons, the splicing and expression level was determined by the same cis additive genetic variance in different tissues. Thus, an effective but simple-to-implement meta-analysis combining information from three tissues is introduced to increase power to detect and validate sQTLs. sQTLs and eeQTLs together were more enriched for variants associated with cattle complex traits, compared to geQTLs. Several putative causal mutations were identified, including an sQTL at Chr6:87392580 within the 5th exon of kappa casein (CSN3) associated with milk production traits. Conclusions Using novel analytical approaches, we report the first identification of numerous bovine sQTLs which are extensively shared between multiple tissue types. The significant overlaps between bovine sQTLs and complex traits QTL highlight the contribution of regulatory mutations to phenotypic variations. |
| first_indexed | 2024-12-21T11:52:15Z |
| format | Article |
| id | doaj.art-aa059d580269463ea5a66f6efccf0f05 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-21T11:52:15Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-aa059d580269463ea5a66f6efccf0f052022-12-21T19:05:01ZengBMCBMC Genomics1471-21642018-07-0119111810.1186/s12864-018-4902-8Genome variants associated with RNA splicing variations in bovine are extensively shared between tissuesRuidong Xiang0Ben J. Hayes1Christy J. Vander Jagt2Iona M. MacLeod3Majid Khansefid4Phil J. Bowman5Zehu Yuan6Claire P. Prowse-Wilkins7Coralie M. Reich8Brett A. Mason9Josie B. Garner10Leah C. Marett11Yizhou Chen12Sunduimijid Bolormaa13Hans D. Daetwyler14Amanda J. Chamberlain15Michael E. Goddard16Faculty of Veterinary & Agricultural Science, University of MelbourneAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, Dairy Production ScienceAgriculture Victoria, Dairy Production ScienceElizabeth Macarthur Agricultural Institute, New South Wales Department of Primary IndustriesAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceAgriculture Victoria, AgriBio, Centre for AgriBioscienceFaculty of Veterinary & Agricultural Science, University of MelbourneAbstract Background Mammalian phenotypes are shaped by numerous genome variants, many of which may regulate gene transcription or RNA splicing. To identify variants with regulatory functions in cattle, an important economic and model species, we used sequence variants to map a type of expression quantitative trait loci (expression QTLs) that are associated with variations in the RNA splicing, i.e., sQTLs. To further the understanding of regulatory variants, sQTLs were compare with other two types of expression QTLs, 1) variants associated with variations in gene expression, i.e., geQTLs and 2) variants associated with variations in exon expression, i.e., eeQTLs, in different tissues. Results Using whole genome and RNA sequence data from four tissues of over 200 cattle, sQTLs identified using exon inclusion ratios were verified by matching their effects on adjacent intron excision ratios. sQTLs contained the highest percentage of variants that are within the intronic region of genes and contained the lowest percentage of variants that are within intergenic regions, compared to eeQTLs and geQTLs. Many geQTLs and sQTLs are also detected as eeQTLs. Many expression QTLs, including sQTLs, were significant in all four tissues and had a similar effect in each tissue. To verify such expression QTL sharing between tissues, variants surrounding (±1 Mb) the exon or gene were used to build local genomic relationship matrices (LGRM) and estimated genetic correlations between tissues. For many exons, the splicing and expression level was determined by the same cis additive genetic variance in different tissues. Thus, an effective but simple-to-implement meta-analysis combining information from three tissues is introduced to increase power to detect and validate sQTLs. sQTLs and eeQTLs together were more enriched for variants associated with cattle complex traits, compared to geQTLs. Several putative causal mutations were identified, including an sQTL at Chr6:87392580 within the 5th exon of kappa casein (CSN3) associated with milk production traits. Conclusions Using novel analytical approaches, we report the first identification of numerous bovine sQTLs which are extensively shared between multiple tissue types. The significant overlaps between bovine sQTLs and complex traits QTL highlight the contribution of regulatory mutations to phenotypic variations.http://link.springer.com/article/10.1186/s12864-018-4902-8RNA splicingGene expressionExpression QTLsQTLGenetic correlationsLocal genomic relationship matrices (LGRM) |
| spellingShingle | Ruidong Xiang Ben J. Hayes Christy J. Vander Jagt Iona M. MacLeod Majid Khansefid Phil J. Bowman Zehu Yuan Claire P. Prowse-Wilkins Coralie M. Reich Brett A. Mason Josie B. Garner Leah C. Marett Yizhou Chen Sunduimijid Bolormaa Hans D. Daetwyler Amanda J. Chamberlain Michael E. Goddard Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues BMC Genomics RNA splicing Gene expression Expression QTL sQTL Genetic correlations Local genomic relationship matrices (LGRM) |
| title | Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues |
| title_full | Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues |
| title_fullStr | Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues |
| title_full_unstemmed | Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues |
| title_short | Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues |
| title_sort | genome variants associated with rna splicing variations in bovine are extensively shared between tissues |
| topic | RNA splicing Gene expression Expression QTL sQTL Genetic correlations Local genomic relationship matrices (LGRM) |
| url | http://link.springer.com/article/10.1186/s12864-018-4902-8 |
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