title: An integrated in silico approach for functional and structural impact of non- synonymous SNPs in the MYH1 gene in Jeju Native Pigs.
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 an in silico analysis, with a focus on (a) in silico approaches to predict the functional effect of non-synonymous SNP (nsSNP) in MYH1 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 in MYH1 from JNP and Berkshire using RNA seq. Gene ontology analysis of MYH1 revealed significant association with muscle contraction and muscle organ development. The 95 % confidence intervals clearly indicate that the mRNA expression of MYH1 is significantly higher in the Berkshire longissimus dorsi muscle samples than JNP breed. Concordant in 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-depth in silico analysis of polymorphic MYH1 and will serve as a valuable resource for further targeted molecular diagnosis and population-based studies conducted for improving the growth performance of JNP.
authors: Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju-Do, 690-756, Republic of Korea. mringhs2010@gmail.com.
authors: Mrinmoy
authors: M
authors: Ghosh
authors: Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju-Do, 690-756, Republic of Korea. simrindersodhi@gmail.com.
authors: Simrinder Singh
authors: SS
authors: Sodhi
authors: Sher-e-Kashmir University of Agricultural Sciences and Technology, R.S. Pura, Jammu, India. drneeleshsharma@gmail.com.
authors: Neelesh
authors: N
authors: Sharma
authors: Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju-Do, 690-756, Republic of Korea. rajkmgr1208@gmail.com.
authors: Raj Kumar
authors: RK
authors: Mongre
authors: Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju-Do, 690-756, Republic of Korea. nameun82@gmail.com.
authors: Nameun
authors: N
authors: Kim
authors: Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju-Do, 690-756, Republic of Korea. ndri.amit@gmail.com.
authors: Amit Kumar
authors: AK
authors: Singh
authors: Department of Animal Biotechnology, College of Animal Bioscience and Technology, Kangwon National University, Chuncheon, 200-701, Republic of Korea. samgenielee@gmail.com.
authors: Sung Jin
authors: SJ
authors: Lee
authors: Livestock Promotion Institute, Jeju Special Self-governing Province, Jeju-Do, 690-756, Republic of Korea. kdc5779@korea.kr.
authors: Dae Cheol
authors: DC
authors: Kim
authors: Animal Genetic Resources Station, National Institute of Animal Science, Rural Administration, Namwon, Republic of Korea. sungwoo@korea.kr.
authors: Sung Woo
authors: SW
authors: Kim
authors: Department of Animal Biotechnology, Chonbuk National University, Jeonju, 561-756, Republic of Korea. breedlee@empal.com.
authors: Hak Kyo
authors: HK
authors: Lee
authors: Department of Animal Biotechnology, Chonbuk National University, Jeonju, 561-756, Republic of Korea. kiduk.song@gmail.com.
authors: Ki-Duk
authors: KD
authors: Song
authors: Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju-Do, 690-756, Republic of Korea. dkjeong@jejunu.ac.kr.
authors: Dong Kee
authors: DK
authors: Jeong
mesh_terms: D000818:Animals; D001947:Breeding; D005260:Female; D063990:Gene Ontology; D015810:Linkage Disequilibrium; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D012984:Software; D013552:Swine / Q000235:genetics* / Q000254:growth & development*
chemical_list: D012333:RNA, Messenger; D018995:Myosin Heavy Chains