Dataset Information

A T > G Mutation in the NR5A2 Gene Is Associated With Litter Size in Hu Sheep Through Upregulation of Promoter Activity by Transcription Factor MTF-1.

ABSTRACT: Nuclear receptor subfamily 5 group A member 2 (NR5A2), also referred to as LRH-1 or FTF, is an orphan nuclear hormone receptor that is involved in regulating embryonic development, ovarian granulosa cell differentiation, gonadal sex differentiation, and steroidogenesis in mammals. However, little is known about how NR5A2 regulates reproduction in sheep. In this study, we amplified the promoter sequence of NR5A2 and determined that its core promoter region ranged from -721 nt to -281 nt. A T > G polymorphism at -700 nt was detected in the core promoter region. Association analysis found that the litter sizes of Hu ewes at their second and average parities with genotype GG (2.20 ± 0.20 and 1.97 ± 0.06, respectively) were significantly higher than those of ewes with genotype TG (1.68 ± 0.10 and 1.74 ± 0.05, respectively) (p < 0.05) and TT (1.67 ± 0.10 and 1.62 ± 0.06, respectively) (p < 0.05). The litter size of Hu ewes at their third parity with genotype GG (2.10 ± 0.10) was significantly higher than that of ewes with genotype TT (1.56 ± 0.12) (p < 0.05). A luciferase assay showed that the -700G allele increased the luciferase activity relative to the -700T allele. Furthermore, the -700T > G polymorphism created a novel binding site for metal-regulatory transcription factor 1 (MTF-1). A competitive electrophoretic mobility shift assay confirmed that MTF-1 specifically bound with the G-type promoter of NR5A2. An overexpression experiment demonstrated that MTF-1 was involved in the alteration of NR5A2 transcription activity and further increased NR5A2 gene mRNA expression. Our findings revealed that the -700T > G polymorphism promoted NR5A2 expression due to the positive effects on NR5A2 gene transcription activity by MTF-1 and thereby increased fecundity in Hu sheep.

SUBMITTER: Li Y

PROVIDER: S-EPMC6824215 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A T > G Mutation in the NR5A2 Gene Is Associated With Litter Size in Hu Sheep Through Upregulation of Promoter Activity by Transcription Factor MTF-1.

Li Yinxia Y Zhang Jun J Qian Yong Y Meng Chunhua C Wang Huili H Zhong Jifeng J Cao Shaoxian S

Frontiers in genetics 20191025

Nuclear receptor subfamily 5 group A member 2 (NR5A2), also referred to as LRH-1 or FTF, is an orphan nuclear hormone receptor that is involved in regulating embryonic development, ovarian granulosa cell differentiation, gonadal sex differentiation, and steroidogenesis in mammals. However, little is known about how NR5A2 regulates reproduction in sheep. In this study, we amplified the promoter sequence of NR5A2 and determined that its core promoter region ranged from -721 nt to -28 ...[more]

PMID: 31708965

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Project description:Background and aimSudanese desert sheep encompass different sheep breeds named according to the different Sudanese tribes that rear them such as the Dubasi, Shugor, and Watish sheep. The objectives of this study were to screen for G1 point mutation in the polymorphic growth differentiation factor 9 (GDF9) gene, investigate its association with litter size, and construct the phylogeny of the different tribal breeds that belong to the Sudanese Desert sheep tribal types.Materials and methodsGenomic DNA was extracted from whole blood of three tribal Desert sheep breeds (Dubasi, Watish, and Shugor) using the guanidine chloride method. Polymerase chain reaction-restriction fragment length polymorphism with HhaI restriction enzyme and sequencing techniques was used for genotyping the GDF9 locus for possible mutations associated with litter size in the three desert sheep tribal types.ResultsG1 mutation in GDF9 caused the replacement of Arginine by Histidine at residue 87. The wild type allele (A) had the highest frequency, whereas the mutant type allele (a) had the lowest in all the sequenced subtypes. The genotype frequencies of the wild type ewes (AA) were higher than the heterozygous (Aa) and the mutant type (aa) frequencies in the three studied desert sheep types. No significant differences were found in the allele frequency between the three tribal types. Litter size was significantly influenced by the genotypes of GDF9 gene, parities, and subtypes (p≤0.01, 0.01, and 0.05, respectively). In the Watish sheep type, heterozygous sheep in their second parity recorded the highest litter size. Sequence alignment of GDF9 gene samples with the database entry indicated that all three tribal types were similar and identical to the reference sequence. The phylogenetic tree revealed that Shugor is the common ancestor of the studied types and Watish is more closely related to Shugor than Dubasi. This result mi ght partly explain the lower reproductive performance of Dubasi compared to Watish and Shugor.ConclusionThe presence of one copy of GDF9 gene increased litter size in the studied Sudanese Desert sheep. This locus may be used as a biomarker for litter size improvement through genotypic selection and allele or gene introgression.

Dataset Information

A T > G Mutation in the NR5A2 Gene Is Associated With Litter Size in Hu Sheep Through Upregulation of Promoter Activity by Transcription Factor MTF-1.

Publications

A T > G Mutation in the <i>NR5A2</i> Gene Is Associated With Litter Size in Hu Sheep Through Upregulation of Promoter Activity by Transcription Factor MTF-1.

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