Polymorphisms of HOMER1 gene are associated with piglet splay leg syndrome and one significant SNP can affect its intronic promoter activity in vitro

Xu, Sutong; Hao, Xingjie; Zhang, Min; Wang, Kai; Li, Shuaifeng; Chen, Xing; Yang, Lu; Hu, Lin; Zhang, Shujun

doi:10.1186/s12863-018-0701-0

Cited by 5 publications

(12 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even though the specific function of HOMER1 has not been studied in pigs sufficiently, it is already known to be involved in muscle differentiation and calcium homeostasis (70), leading to myopathy in mice when expression is lost (71) and exhibited lower expression in a mouse model of Duchenne's muscular dystrophy (72). A follow up study (73) focused directly on the sequence of porcine HOMER1, defined the promoter regions and analyzed a total of 21 SNPs in the same population used in their previous analysis (17). Twelve of the SNPs were significantly associated with PCS making HOMER1 a promising candidate for PCS ( Table 2).…”

Section: Genetic Characterization Of the Splay Leg Syndromementioning

confidence: 99%

“…FBXO32 was not only identified in targeted as well as in global transcriptome analyses (5, 16) but its chromosomal region harbors genetic variants (66). HOMER1 was also found to contain specific SNPs using GWAS (17) which seem to alter the expression of certain isoforms via a modified intronic promotor (73). All studies were performed in different populations indicating a general validity (Tables 1, 2).…”

Section: Current Statusmentioning

confidence: 99%

“…This may lead to improper muscle innervation as reported by Szalay et al (41) for PCS piglets. Since certain SNPs have already been reported near or within the HOMER locus (17) and also seem to effectively modulate Homer isoform expression (73), this candidate might be the most promising in the search for the cause of the hereditary trait of PCS.…”

Section: Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

Congenital Splay Leg Syndrome in Piglets—Current Knowledge and a New Approach to Etiology

2021

View full text Add to dashboard Cite

The porcine congenital splay leg syndrome (PCS), even though being of transient nature, is still one of the most important causes for piglet losses due to its high incidence and mortality. Although, described decades ago, the pathogenetic mechanism is still elusive. Numerous, mostly descriptive studies characterized the syndrome at clinical, histological and cellular levels but resulted in a highly diverse picture of the syndrome. Broad variability in phenotypical expression and, in case of proper care, the rapid recovery of affected animals complicated a systematical analysis of the underlying pathogenesis. Although, several environmental factors were discussed as potential causes of PCS, most of the evidence points to a hereditary basis of PCS. Nevertheless, only few of the suggested candidate genes from transcriptome and mapping analyses, like F-box protein 32 (FBXO32), could be confirmed so far. Only recently, a genome wide association study revealed genomic regions on five porcine chromosomes and named a number of potential candidate genes, among them homer scaffold protein 1 (HOMER1). This new candidate—a cellular scaffold protein—plays a role in a plethora of cellular signaling cascades, and is not only involved in skeletal muscle differentiation but also critical for muscular function. In this review, we critically elucidate the current state of knowledge in the field and evaluate current achievements in the identification of the pathogenetic mechanism for the syndrome.

show abstract

Section: Genetic Characterization Of the Splay Leg Syndromementioning

confidence: 99%

Section: Current Statusmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

See 1 more Smart Citation

Congenital Splay Leg Syndrome in Piglets—Current Knowledge and a New Approach to Etiology

2021

View full text Add to dashboard Cite

show abstract

“…Further analysis showed that -700G created a transcription factor MTF-1 binding site and MTF-1 was involved in regulating NR5A2 promoter transcription activity, increasing the NR5A2 gene expression in granulosa cells of sheep. Xu et al (2018) found that polymorphisms of the HOMER1 gene are associated with piglet splay leg syndrome and the G allele of rs325197091 (A > G) may create a new binding site of transcription factor ARNT, which could enhance HOMER1 promoter activity and expression. Promoter haplotypes of the ABCB1 gene encoding the P-glycoprotein differentially affects its promoter activity by altering the transcription factor binding (Speidel et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Qian

et al. 2019

Front. Genet.

View full text Add to dashboard Cite

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.

show abstract

“…enhancer50 or affecting promoter activity,51 according to the results of the ENCODE database. In addition, overexpressed HDAC9 may dysregulate the functions of downstream genes, and aberrant expression of HDAC9 may regulate infiltration of CD4 + T cells and Tregs to affect tumor microenvironment and therefore affect the OS of ESCC patients.…”

mentioning

confidence: 99%

Potentially functional genetic variants of the notch signaling pathway genes predict survival of Chinese patients with esophageal squamous cell carcinoma

Liu

Zhang

et al. 2022

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background The Notch signaling pathway is involved in the progression of esophageal squamous cell carcinoma (ESCC), although the roles of single nucleotide polymorphisms (SNPs) of the Notch signaling pathway genes in the process remain unknown. Methods The present study included 1009 patients with histopathologically diagnosed ESCC at Fudan University Shanghai Cancer Center. Two‐stage multivariate Cox proportional hazards regression analysis was used to estimate associations between 13,248 SNPs in 103 Notch signaling pathway genes and overall survival of the patients. Results We found that overall survival of the patients was significantly associated with genotypes of HDAC9 rs1729318 (AT+TT vs. AA: hazard ratio = 1.44, 95% confidence interval = 1.16–1.80, pcombined = 0.001) and HDAC9 rs1339555498 (GT + TT vs. GG: hazard ratio = 1.38, 95% confidence interval = 1.10–1.74, pcombined = 0.005). Further receiver operator characteristic (ROC) curve analysis indicated that the model with both available clinical factors and these two SNPs improved the area under the ROC curve compared to the model with clinical factors only (1‐year: 0.66 vs. 0.64, p = 0.034). Additional expression quantitative trait loci analysis showed that the rs1729318 T variant genotypes were associated with increased mRNA expression levels of HDAC9 in normal esophageal muscular tissue (p = 0.003). Conclusions The results suggest that these two potential functional SNPs on HDAC9 may serve as biomarkers for predicting survival of ESCC patients. However, further studies are needed to confirm these findings.

show abstract

Polymorphisms of HOMER1 gene are associated with piglet splay leg syndrome and one significant SNP can affect its intronic promoter activity in vitro

Cited by 5 publications

References 19 publications

Congenital Splay Leg Syndrome in Piglets—Current Knowledge and a New Approach to Etiology

Congenital Splay Leg Syndrome in Piglets—Current Knowledge and a New Approach to Etiology

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

Potentially functional genetic variants of the notch signaling pathway genes predict survival of Chinese patients with esophageal squamous cell carcinoma

Contact Info

Product

Resources

About