Editing porcine IGF2 regulatory element improved meat production in Chinese Bama pigs

Xiang, Guanghai; Ren, Jilong; Hai, Tang; Fu, Rui; Yu, Dawei; Wang, Jing; Li, Wei; Wang, Haoyi; Zhou, Qi

doi:10.1007/s00018-018-2917-6

Cited by 62 publications

(44 citation statements)

References 32 publications

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“…Prior studies found that introns had a positive effect on gene expression in various ways; for example, a nucleotide mutation in intron 3 of porcine IGF2 could affect skeletal muscle by specifically binding to the transcription factor ZBED6 protein [8,36]. Similarly, we wanted to investigate whether this mutation site could affect transcription factor binding differently.…”

Section: Discussionmentioning

confidence: 99%

Screening of Deletion Variants within the Goat PRDM6 Gene and Its Effects on Growth Traits

Wang

Guo

et al. 2020

Animals

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Simple Summary: Genome-wide association studies found that the PR/SET Domain 6 (PRDM6) gene mutation was associated with bone development, bone density, and body mass index. This study found a 12 bp deletion variation within the PRDM6 gene in Shaanbei white cashmere goats in a large sample size (n = 1044). This variation polymorphism was associated with multiple goat growth traits in the yearling period, including heart girth (p = 0.027), cannon circumference (p = 0.008), chest depth (p = 2.10 × 10 −5 ), chest width (p = 0.004), body height (p = 0.032), body length (p = 0.044), and hip-width (p = 0.014). The effects of the 12 bp variation were found to make no difference on adult goat growth traits. Taken together, these results demonstrate that the 12 bp deletion variant plays an important role in the early growth and development of goats and could be considered as a useful and effective molecular marker for goat breeding selection in the growth stage.Abstract: By genome-wide association studies, the PRDM6 gene has been shown to affect multiple, apparently unrelated inherited traits, including bone density and body mass index. Therefore, it is considered a potentially pleiotropic gene. In this study, we identified a 12 bp deletion variant (NC_030814.1:rs651603667, g: 79985625-79985636delTTGACTGATCCA) within the PRDM6 gene in a large sample (SBWC goats; n = 1044). All goat samples were collected in Shaanxi province in July 2018. The frequency of the wt allele was higher than the frequency of the del allele, and this mutation polymorphism confirmed to be consistent with the Hardy-Weinberg equilibrium (p > 0.05). Further results showed that in a group of goats in the yearling period (18 months old, n = 567), this deletion variant of the PRDM6 gene was associated with heart girth (p = 0.027), cannon circumference (p = 0.008), chest depth (p = 2.10 × 10 −5 ), chest width (p = 0.004), body height (p = 0.032), body length (p = 0.044) and hip-width (p = 0.014). For adult SBWC goats (36 months old, n = 477), the effects of the 12 bp variation on growth-related traits were found to make no difference. These findings show that the 12 bp deletion within the goat PRDM6 gene plays an important role in the early growth and development of goats. Using the 12 bp mutation, breeders can quickly and effectively select excellent individual goats at an early stage.

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Section: Discussionmentioning

confidence: 99%

Screening of Deletion Variants within the Goat PRDM6 Gene and Its Effects on Growth Traits

Wang

Guo

et al. 2020

Animals

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“…For example, insulin-like growth factor 2 (IGF2) plays an important role in cell proliferation and differentiation [71]. Using CRISPR/Cas9 gene editing to upregulate IGF2 gene expression can accelerate the growth of pigs [29,72]. Myostatin (MSTN) plays an important negative regulatory role in the proliferation, differentiation, and growth of animal skeletal muscles.…”

Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9-Mediated Biallelic Knockout of IRX3 Reduces the Production and Survival of Somatic Cell-Cloned Bama Minipigs

Zhu

Wei

Zhan

et al. 2020

Animals

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Simple Summary: Bama minipigs are a local pig breed that is unique to China and possess several negative features, including high fat content, low feed utilization rate, and slow growth rate. The iroquois homeobox 3 (IRX3) gene has been implicated in human obesity and controls body mass and composition in mouse. In this study, we successfully generated IRX3 biallelic knockout Bama minipigs using CRISPR/Cas9-mediated gene editing combined with somatic cell cloning. The results show that the use of IRX3 -/cells as donor cells for the production of somatic cell-cloned pigs induces a significant decrease in the average live litter size and a significant increase in the average number of stillbirths. Moreover, the birth weight of surviving IRX3 -/somatic cell-cloned pigs is significantly lower, and viability is poor such that all piglets die shortly after birth. Therefore, the preliminary results of this study suggest that IRX3 may have important biological functions in pigs, and IRX3 should not be used as a gene editing target to reduce fat content in Bama minipigs.Abstract: Bama minipigs are a local pig breed that is unique to China and has a high development and utilization value. However, its high fat content, low feed utilization rate, and slow growth rate have limited its popularity and utilization. Compared with the long breeding cycle and high cost of traditional genetic breeding of pigs, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) endonuclease 9 system (CRISPR/Cas9)-mediated gene editing can cost-effectively implement targeted mutations in animal genomes, thereby providing a powerful tool for rapid improvement of the economic traits of Bama minipigs. The iroquois homeobox 3 (IRX3) gene has been implicated in human obesity. Mouse experiments have shown that knocking out IRX3 significantly enhances basal metabolism, reduces fat content, and controls body mass and composition. This study aimed to knock out IRX3 using the CRISPR/Cas9 gene editing method to breed Bama minipigs with significantly reduced fat content. First, the CRISPR/Cas9 gene editing method was used to efficiently obtain IRX3 -/cells. Then, the gene-edited cells were used as donor cells to produce surviving IRX3 -/-Bama minipigs using somatic cell cloning. The results show that the use of IRX3 -/cells as donor cells for the production of somatic cell-cloned pigs results in a significant decrease in the average live litter size and a significant increase in the average number of stillbirths. Moreover, the birth weight of surviving IRX3 -/somatic cell-cloned pigs is significantly lower, and viability is poor such that all piglets die shortly after birth. Therefore, the preliminary results of this study suggest that IRX3 may have important biological functions in pigs, and IRX3 should not be used as a gene editing target to reduce fat content in Bama minipigs. Moreover, this study shows that knocking out IRX3 does not favor the survival of pigs, and whether targeted regulation of IRX3 in the treatment o...

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“…Some studies have reported that polymorphisms within intron region had positive effects on gene expression and affected many economic traits of livestock by various ways (Kalkan et al, 2013;Kanzi et al, 2016;Vaz-Drago et al, 2017). The representative example is a nucleotide substitution in intron 3 of porcine IGF2 significantly affecting skeletal muscle by transcription factor called ZBED6 (Van Laere et al, 2003;Xiang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Detection of genetic variations of five MMAF-related genes and their associations with litter size in goat

Wang

Peng

et al. 2019

Preprint

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Background: Multiple morphological abnormalities of the sperm flagella (MMAF) makes an assignable contribution to male infertility, including QRICH2 , CFAP43 , CFAP44 , CFAP69 , CCDC39 , AKAP4 and DNAH1 gene. This work studied 28 putative indel mutations of MMAF related genes including QRICH2 , CFAP69 , CFAP43 , CCDC39 and DNAH1 gene and their correlation with the first-born litter sizes of 769 Shaanbei white cashmere (SBWC) goats. Results: Electrophoresis and DNA sequencing analysis showed the 11-bp indel within QRICH2 ( QRICH2 -P4), the three indel variations in CFAP69 ( CFAP69 -P4, CFAP69 -P6 and CFAP69 -P7) and the 27-bp indel of DNAH1 ( DNAH1 -P1) were found to be polymorphic. The 27-bp indel variation within DNAH1 was not in consistent with HWE and the other four indel of QRICH2 and CFAP69 were in consistent with HWE. The linkage disequilibrium (LD) analysis showed the 8-bp indel ( CFAP69 -P4) and the 6-bp indel ( CFAP69- P6) within CFAP69 were in complete LD with each other (D'=0.99, r 2 =1.00). The 27-bp indel mutation within DNAH1 was strongly significantly associated with first-born litter sizes of SBWC goats ( P ＜0.01) and the average litter size of II genotype was significantly greater than ID and DD genotypes ( P = 0.003). In single-lamb and multi-lamb of goat groups, the genotype distributions of the 27-bp indel was significantly different ( P = 0.002). While the 11-bp indel variation of QRICH2 and three indel mutations (P4, P6 and P7) of CFAP69 identified were not ( P ＞0.05). Conclusions: These findings suggest the 27-bp indels in the goat DNAH1 can be used as an effective molecular marker for marker-assisted selection of goats reproduction breeding in the future.

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Editing porcine IGF2 regulatory element improved meat production in Chinese Bama pigs

Cited by 62 publications

References 32 publications

Screening of Deletion Variants within the Goat PRDM6 Gene and Its Effects on Growth Traits

Screening of Deletion Variants within the Goat PRDM6 Gene and Its Effects on Growth Traits

CRISPR/Cas9-Mediated Biallelic Knockout of IRX3 Reduces the Production and Survival of Somatic Cell-Cloned Bama Minipigs

Detection of genetic variations of five MMAF-related genes and their associations with litter size in goat

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