A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes

Ran Li; Mian Gong; Xinmiao Zhang; Fei Wang; Zhenyu Liu; Lei Zhang; Qimeng Yang; Yuan Xu; Mengsi Xu; Huanhuan Zhang; Yunfeng Zhang; Xuelei Dai; Yuanpeng Gao; Zhuangbiao Zhang; Wenwen Fang; Yuta Yang; Weiwei Fu; Chunna Cao; Peng Yang; Zeinab Amiri Ghanatsaman; Niloufar Jafarpour Negari; Hojjat Asadollahpour Nanaei; Xiangpeng Yue; Yuxuan Song; Xianyong Lan; Weidong Deng; Xihong Wang; Chuanying Pan; Ruidong Xiang; Eveline M Ibeagha-Awemu; Pat J S Heslop-Harrison; Benjamin D Rosen; Johannes A Lenstra; Shangquan Gan; Yu Jiang

doi:10.1101/gr.277372.122

A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes

Ran Li, Mian Gong, Xinmiao Zhang, Fei Wang, Zhenyu Liu, Lei Zhang, Qimeng Yang, Yuan Xu, Mengsi Xu, Huanhuan Zhang, Yunfeng Zhang, Xuelei Dai, Yuanpeng Gao, Zhuangbiao Zhang, Wenwen Fang, Yuta Yang, Weiwei Fu, Chunna Cao, Peng Yang, Zeinab Amiri GhanatsamanNiloufar Jafarpour Negari, Hojjat Asadollahpour Nanaei, Xiangpeng Yue, Yuxuan Song, Xianyong Lan, Weidong Deng, Xihong Wang, Chuanying Pan, Ruidong Xiang, Eveline M Ibeagha-Awemu, Pat J S Heslop-Harrison, Benjamin D Rosen, Johannes A Lenstra, Shangquan Gan^*, Yu Jiang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5' untranslated region (5' UTR) of HOXB13 is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep.

Original language	English
Pages (from-to)	463-477
Number of pages	15
Journal	Genome Research
Volume	33
Issue number	3
DOIs	https://doi.org/10.1101/gr.277372.122
Publication status	Published - Mar 2023

Bibliographical note

Funding Information:
This study was supported by research grants from the National Key R&D Program of China (2022YFF1000100), the National Natural Science Foundation of China (U21A20247, 31822052), and the Livestock Breeding Program of Shaanxi (2022GD-TSLD-46) to Y.J., S.Q.G. (31760662, 31860639), and R.L. (31802027), Natural Science Basic Research Program of Shaanxi (K3030121801) to Y.J., and China Postdoctoral Science Foundation to W.W. Fu (No. 2021M702690). We thank the High-Performance Computing platform of Northwest A&F University and Hefei advanced computing center for providing computing resources. We also thank Professor X. Wang for providing the chart of different sheep tail patterns and Mr. Guochun Wang (Animal Husbandry Technology Extension Station of Chaoyang City) for help in collecting samples.

Publisher Copyright:
© 2023 Li et al.

Keywords

Animals
Sheep/genetics
Genome-Wide Association Study
Tail
5' Untranslated Regions
Alleles
Phenotype

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10.1101/gr.277372.122Licence: CC BY-NC

Genome Res.-2023-Li-463-77Final published version, 4.22 MBLicence: CC BY-NC

Cite this

Li, R., Gong, M., Zhang, X., Wang, F., Liu, Z., Zhang, L., Yang, Q., Xu, Y., Xu, M., Zhang, H., Zhang, Y., Dai, X., Gao, Y., Zhang, Z., Fang, W., Yang, Y., Fu, W., Cao, C., Yang, P., ... Jiang, Y. (2023). A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes. Genome Research, 33(3), 463-477. https://doi.org/10.1101/gr.277372.122

@article{172c362373c249e69299222c3c138d48,

title = "A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes",

abstract = "Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5' untranslated region (5' UTR) of HOXB13 is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep. ",

keywords = "Animals, Sheep/genetics, Genome-Wide Association Study, Tail, 5' Untranslated Regions, Alleles, Phenotype",

author = "Ran Li and Mian Gong and Xinmiao Zhang and Fei Wang and Zhenyu Liu and Lei Zhang and Qimeng Yang and Yuan Xu and Mengsi Xu and Huanhuan Zhang and Yunfeng Zhang and Xuelei Dai and Yuanpeng Gao and Zhuangbiao Zhang and Wenwen Fang and Yuta Yang and Weiwei Fu and Chunna Cao and Peng Yang and Ghanatsaman, {Zeinab Amiri} and Negari, {Niloufar Jafarpour} and Nanaei, {Hojjat Asadollahpour} and Xiangpeng Yue and Yuxuan Song and Xianyong Lan and Weidong Deng and Xihong Wang and Chuanying Pan and Ruidong Xiang and Ibeagha-Awemu, {Eveline M} and Heslop-Harrison, {Pat J S} and Rosen, {Benjamin D} and Lenstra, {Johannes A} and Shangquan Gan and Yu Jiang",

note = "Funding Information: This study was supported by research grants from the National Key R&D Program of China (2022YFF1000100), the National Natural Science Foundation of China (U21A20247, 31822052), and the Livestock Breeding Program of Shaanxi (2022GD-TSLD-46) to Y.J., S.Q.G. (31760662, 31860639), and R.L. (31802027), Natural Science Basic Research Program of Shaanxi (K3030121801) to Y.J., and China Postdoctoral Science Foundation to W.W. Fu (No. 2021M702690). We thank the High-Performance Computing platform of Northwest A&F University and Hefei advanced computing center for providing computing resources. We also thank Professor X. Wang for providing the chart of different sheep tail patterns and Mr. Guochun Wang (Animal Husbandry Technology Extension Station of Chaoyang City) for help in collecting samples. Publisher Copyright: {\textcopyright} 2023 Li et al.",

year = "2023",

month = mar,

doi = "10.1101/gr.277372.122",

language = "English",

volume = "33",

pages = "463--477",

journal = "Genome Research",

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number = "3",

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Li, R, Gong, M, Zhang, X, Wang, F, Liu, Z, Zhang, L, Yang, Q, Xu, Y, Xu, M, Zhang, H, Zhang, Y, Dai, X, Gao, Y, Zhang, Z, Fang, W, Yang, Y, Fu, W, Cao, C, Yang, P, Ghanatsaman, ZA, Negari, NJ, Nanaei, HA, Yue, X, Song, Y, Lan, X, Deng, W, Wang, X, Pan, C, Xiang, R, Ibeagha-Awemu, EM, Heslop-Harrison, PJS, Rosen, BD, Lenstra, JA, Gan, S & Jiang, Y 2023, 'A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes', Genome Research, vol. 33, no. 3, pp. 463-477. https://doi.org/10.1101/gr.277372.122

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T1 - A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes

AU - Li, Ran

AU - Gong, Mian

AU - Zhang, Xinmiao

AU - Wang, Fei

AU - Liu, Zhenyu

AU - Zhang, Lei

AU - Yang, Qimeng

AU - Xu, Yuan

AU - Xu, Mengsi

AU - Zhang, Huanhuan

AU - Zhang, Yunfeng

AU - Dai, Xuelei

AU - Gao, Yuanpeng

AU - Zhang, Zhuangbiao

AU - Fang, Wenwen

AU - Yang, Yuta

AU - Fu, Weiwei

AU - Cao, Chunna

AU - Yang, Peng

AU - Ghanatsaman, Zeinab Amiri

AU - Negari, Niloufar Jafarpour

AU - Nanaei, Hojjat Asadollahpour

AU - Yue, Xiangpeng

AU - Song, Yuxuan

AU - Lan, Xianyong

AU - Deng, Weidong

AU - Wang, Xihong

AU - Pan, Chuanying

AU - Xiang, Ruidong

AU - Ibeagha-Awemu, Eveline M

AU - Heslop-Harrison, Pat J S

AU - Rosen, Benjamin D

AU - Lenstra, Johannes A

AU - Gan, Shangquan

AU - Jiang, Yu

N1 - Funding Information: This study was supported by research grants from the National Key R&D Program of China (2022YFF1000100), the National Natural Science Foundation of China (U21A20247, 31822052), and the Livestock Breeding Program of Shaanxi (2022GD-TSLD-46) to Y.J., S.Q.G. (31760662, 31860639), and R.L. (31802027), Natural Science Basic Research Program of Shaanxi (K3030121801) to Y.J., and China Postdoctoral Science Foundation to W.W. Fu (No. 2021M702690). We thank the High-Performance Computing platform of Northwest A&F University and Hefei advanced computing center for providing computing resources. We also thank Professor X. Wang for providing the chart of different sheep tail patterns and Mr. Guochun Wang (Animal Husbandry Technology Extension Station of Chaoyang City) for help in collecting samples. Publisher Copyright: © 2023 Li et al.

PY - 2023/3

Y1 - 2023/3

N2 - Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5' untranslated region (5' UTR) of HOXB13 is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep.

AB - Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5' untranslated region (5' UTR) of HOXB13 is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep.

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KW - Sheep/genetics

KW - Genome-Wide Association Study

KW - Tail

KW - 5' Untranslated Regions

KW - Alleles

KW - Phenotype

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JO - Genome Research

JF - Genome Research

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ER -

A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes

Abstract

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Keywords

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