Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Dong, Kunzhe; Yang, Min; Han, Jiangang; Ma, Qing; Han, Jilong; Song, Ziyi; Luosang, Cuicheng; Gorkhali, Neena Amatya; Yang, Bo‐Yi; He, Xiaoyan; Ma, Yuehui; Jiang, Lin

doi:10.21203/rs.3.rs-36111/v4

Cited by 7 publications

(32 citation statements)

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“…5c), of which the largest one is a 7728 bp insertion. PDGFD has been recognized as the most plausible candidate gene for the fat-tail phenotype in recent studies 23, 55 . We found three highly differentiated SVs residing in the selective region of PDGFD , of which the largest event is a 867 bp insertion.…”

Section: Resultsmentioning

confidence: 99%

The first sheep graph-based pan-genome reveals the spectrum of structural variations and their effects on tail phenotypes

Gong

Zhang

et al. 2021

Preprint

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Structural variations (SVs) are a major contributor of genetic diversity and phenotypic variations, however their prevalence and functions in domestic animals are largely unexplored. Here, we assembled 26 haplotype-resolved genome assemblies from 13 genetically diverse sheep breeds using PacBio HiFi sequencing. We then constructed an ovine graph pan-genome and demonstrated its advantage in discovering 142,593 biallelic SVs (Insertions and deletions), 7,028 divergent alleles and 13,419 multiallelic variations with high accuracy and sensitivity. To link the SVs to genotypes, we genotyped the SVs in 687 resequenced individuals of domestic and wild sheep using a graph-based approach and identified numerous population-stratified variants, of which expression-associated SVs were detected by integrating RNA-seq data. Taking the varying sheep tail morphology as example, we located a putative causative insertion in HOXB13 gene responsible for the long tail and reported multiple large SVs associated with the fat tail. Beyond generating a benchmark resource for ovine structural variants, our study also highlighted that the population genetics analysis based on graph pan-genome rather than reference genome will greatly benefit the animal genetic research.

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Section: Resultsmentioning

confidence: 99%

The first sheep graph-based pan-genome reveals the spectrum of structural variations and their effects on tail phenotypes

Gong

Zhang

et al. 2021

Preprint

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“…Dong et al (2020b) recently investigated the PDGFD gene using an extended data set of 968 sheep (18 and 14 fat-and thin-tailed breeds, respectively, worldwide). They showed an association with the fat tail phenotype (Dong et al 2020b). Here, four significant points about the PDGFD gene were highlighted: (i) between fat-tailed and thin-tailed breeds, a 6.8-kb region within the first intron of the PDGFD gene contains the most differentiated SNPs and it probably has a regulatory mutation(s) for fat tail patterning [notably, there was also an indication of a highly differentiated SNP, Chr15:3859314T>C; Oar_v3.1, in the preprint (Dong et al, 2020a)]; (ii) between embryonic days 60 and 70, the expression of the PDGFD gene was high in the tail of sheep (a fat-tailed type); hence it is potentially responsible for the initiation and/or commitment of preadipocytes; (iii) at days 80 and 90 of the embryonic stage, the PDGFD gene was negatively associated with fat maturation since the expression of this gene reduced when fat started accumulating in the tail of sheep (a fat-tailed type); and (iv) generally, the expression of the PDGFD gene is higher in fat-tailed breeds than in thin-tailed breeds, and a similar result was observed in obese mice and humans after analyzing a public transcriptomic data (Dong et al 2020b).…”

Section: Bmp2 As a Potential Candidate Gene For The Sheep Fattail Phenotypementioning

confidence: 99%

“…Towards a better elucidation of the expression nature of sheep tail candidate genes Dong et al (2020b) provided novel insights into the association of the PDGFD gene and the tail phenotype during the early developmental stages of fat-tailed sheep (a local Chinese breed; Tan sheep). This was achieved by performing histological and gene expression analyses of tail fat tissues.…”

Section: Towards a Better Elucidation Of Variant Causalities Of Sheep Fat-tail Patternmentioning

confidence: 99%

“…The low-fat content in the tail of thin-tailed sheep breeds could be the reason for its absence in the comparison. Dong et al (2020b) showed that the gene expression of the PDGFD gene varies at different developmental stages; thus, the age of the examined individuals should be considered. In the follow-up investigations, these points can be considered to precisely determine the association between the PDGFD gene expression profiles and sheep tail phenotypic patterns.…”

Section: Towards a Better Elucidation Of Variant Causalities Of Sheep Fat-tail Patternmentioning

confidence: 99%

“…Here, the RNA‐seq results did not show a specific oscillation for the BMP2 gene expression (Dong et␣al . 2020b). Based on the reanalysis of previously reported BMP2 ‐associated SNPs and the BMP2 expression profile during embryonic development, Dong et␣al .…”

Section: Telling the Tale Of Tail In Sheep: Genomic Insightsmentioning

confidence: 99%

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Trends towards revealing the genetic architecture of sheep tail patterning: Promising genes and investigatory pathways

et al. 2021

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Different sheep breeds have evolved after initial domestication, generating various tail phenotypic patterns. The phenotypic diversity of sheep tail patterns offers ideal materials for comparative analysis of its genetic basis. Evolutionary biologists, animal geneticists, breeders, and producers have been curious to clearly understand the underlying genetics behind phenotypic differences in sheep tails. Understanding the causal gene(s) and mutation (s) underlying these differences will help probe an evolutionary riddle, improve animal production performance, promote animal welfare, and provide lessons that help comprehend human diseases related to fat deposition (i.e., obesity). Historically, fat tails have served as an adaptive response to aridification and climate change. However, the fat tail is currently associated with compromised mating and animal locomotion, fat distribution in the animal body, increased raising costs, reduced consumer preference, and other animal welfare issues such as tail docking. The developing genomic approaches provide unprecedented opportunities to determine causal variants underlying phenotypic differences among populations. In the last decade, researchers have performed several genomic investigations to assess the genomic causality underlying phenotypic variations in sheep tails. Various genes have been suggested with the prominence of several potentially significant causatives, including the BMP2 and PDGFD genes associated with the fat tail phenotype and the TBXT gene linked with the caudal vertebrae number and tail length. Although the potential genes related to sheep tail characteristics have been revealed, the causal variant(s) and mutation(s) of these high-ranking candidate genes are still elusive and need further investigation. The review discusses the potential genes, sheds light on a knowledge gap, and provides possible investigative approaches that could help determine the specific genomic causatives of sheep tail patterns. Besides, characterizing and revealing the genetic determinism of sheep tails will help solve issues compromising sheep breeding and welfare in the future.

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Ovine HOXB13: expanding the gene repertoire of sheep tail patterning and implications in genetic improvement

et al. 2022

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Understanding the genetic basis of sheep tails is of great importance to improve sheep production and welfare. In this Comment, we discussed recent findings showing that homeobox B13 (HOXB13) is a regulator of the tail length in sheep. The revelation of the HOXB13 gene adds novel insights into the genetic determinism of the sheep tail phenotype. This new genetic highlight will lead to further advances in sheep breeding using selection-based strategies and molecular genetics-based tools.A brief background: piecing together the genetic structure of sheep tail formation The tail phenotype, an obvious body segment, has been described as a significantly divergent trait in sheep 1 , which is due to the wide phenotypic diversity of sheep tails among different breeds located within various geographical and environmental regions 2 . Several factors influence the sheep tail phenotype, including length, fat deposition level, and directionality. The overall tail length is controlled by the number and length of caudal vertebrae. On the other hand, tail fat deposition is controlled by the size and number of adipocytes. Several tail phenotypic patterns have been shown in sheep, including the thin-long tail, thin-short tail, fat-short tail, fat-long tail, and fat-rumped tail (Fig. 1, upper panel). Studies have been performed to understand the mechanistic determinism of sheep tails based on genetic basis, due to the association of sheep tails with several raising-related and welfare issues (see reviews by refs. [3][4][5][6] ). Of these issues, tail docking, as a painful practice, is the most critical 5,6 . Revealing the genetic determinism of sheep tails will help to direct the selection towards the desired phenotypes 7,8 and provide access to new biotechnological tools to directly introduce the desired variant(s) into the targeted breed 9,10 . Recently, three genes/regions were reported to be significantly associated with the sheep tail phenotype. These include the platelet derived growth factor D (PDGFD) gene 1,11,12 and the intergenic region between the bone morphogenetic protein 2 (BMP2) and hydroxyacid oxidase 1 (HAO1) genes, referred to as the IBH region [13][14][15] linked with the fat-tail phenotype, and the T-box transcription factor T (TBXT) gene [16][17][18] linked with variations in caudal vertebrae. Recent studies highlighted a new gene, HOXB13, which is highly associated with the sheep tail length [19][20][21][22][23] (Table 1). Of these studies, two independent efforts, one recently published in Communications Biology 23 and the other published as a preprint 21 , strongly highlighted a structural variation (SV) in the form of a short insertion associated with the longtail phenotype, adding a new critical member to the gene repertoire of the sheep tail configuration.

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Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep

Cited by 7 publications

References 2 publications

The first sheep graph-based pan-genome reveals the spectrum of structural variations and their effects on tail phenotypes

The first sheep graph-based pan-genome reveals the spectrum of structural variations and their effects on tail phenotypes

Trends towards revealing the genetic architecture of sheep tail patterning: Promising genes and investigatory pathways

Ovine HOXB13: expanding the gene repertoire of sheep tail patterning and implications in genetic improvement

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