An integrated in silico approach for functional and structural impact of non- synonymous SNPs in the MYH1 gene in Jeju Native Pigs. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Ghosh, Mrinmoy; Sodhi, Simrinder; Sharma, Neelesh; Mongre, Raj; Kim, Nameun; Singh, Amit; Lee, Sung; Kim, Dae; Kim, Sung; Lee, Hak; Song, Ki-Duk; Jeong, Dong
• Is Part Of: BMC genetics. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 16
• Publication Date: 2016-12
• Subjects: MYH1 -- Non-synonymous SNPs -- Protein-protein interaction -- Homologous modeling -- Molecular dynamic simulation; Genetics -- Periodicals; 576.505
• DOI: 10.1186/s12863-016-0341-1
• Languages: English
• ISSNs: 1471-2156

Abstract

Abstract Background This study was performed to identify the non- synonymous polymorphisms in the myosin heavy chain 1 gene (MYH1 ) association with skeletal muscle development in economically important Jeju Native Pig (JNP) and Berkshire breeds. Herein, we present anin silico analysis, with a focus on (a)in silico approaches to predict the functional effect of non-synonymous SNP (nsSNP) inMYH1 on growth, and (b) molecular docking and dynamic simulation of MYH1 to predict the effects of those nsSNP on protein-protein association. Results The NextGENe (V 2.3.4.) tool was used to identify the variants inMYH1 from JNP and Berkshire using RNA seq. Gene ontology analysis ofMYH1 revealed significant association with muscle contraction and muscle organ development. The 95 % confidence intervals clearly indicate that the mRNA expression ofMYH1 is significantly higher in the Berkshirelongissimus dorsi muscle samples than JNP breed. Concordantin silico analysis of MYH1, the open-source software tools identified 4 potential nsSNP (L884T, K972C, N981G, and Q1285C) in JNP and 1 nsSNP (H973G) in Berkshire pigs. Moreover, protein-protein interactions were studied to investigate the effect of MYH1 mutations on association with hub proteins, and MYH1 was found to be closely associated with the protein myosin light chain, phosphorylatable, fast skeletal muscle MYLPF. The results of molecular docking studies on MYH1 (native and 4 mutants) and MYLFP demonstrated that the native complex showed higher electrostatic energy (−466.5 Kcal mol−1 ), van der Walls energy (−87.3 Kcal mol−1 ), and interaction energy (−835.7 Kcal mol−1 ) than the mutant complexes. Furthermore, the molecular dynamic simulation revealed that the native complex yielded a higher root-mean-square deviation (0.2–0.55 nm) and lower root-mean-square fluctuation (approximately 0.08–0.3 nm) as compared to the mutant complexes. Conclusions The results suggest that the variants at L884T, K972C, N981G, and Q1285C in MYH1 in JNP might represent a cause for the poor growth performance for this breed. This study is a pioneering in-depthin silico analysis of polymorphicMYH1 and will serve as a valuable resource for further targeted molecular diagnosis and population-based studies conducted for improving the growth performance of JNP.