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314Leptin is a versatile hormone that regulates several metabolic pathways such as controlling body weight feed intake energy expenditure immune function and reproduction In spite of exhaustive studies that performed on the bovine LEP gene no attempt has been made to comprehensively and systematically analyze its entire coding SNPs The present study was carried out to identify the most deleterious non synonymous SNPs nsSNPs of bovine LEP gene To predict the possible impact of missense mutations on leptin structure and function SNPs data that obtained from dbSNP database were analyzed using various bioinformatics tools The total nsSNPs that considered for the present study were 28 It was found that 9 nsSNPs including R66M H91N H91P A104V S162P D186Y D186G C191S and C191G in 6 amino acid positions were found to be deleterious and damaging by four common nsSNPs prediction tools and thus affecting leptin protein structure and biological activity I Mutant 2 eliminated two nsSNPs including S12P and D16Y since they increase protein stability upon mutation Further information regarding the residual deleterious nsSNPs showed that three of these variants including R66M C191S and C191G were confirmed that they were located in very high conserved positions and thus the mutations in these amino acids positions have deleterious evolutionary consequences The findings of the present study proved that R66M C191S and C191G nsSNPs have the most considerable deleterious consequences on both structure and function of bovine leptin
The present study provides the first comprehensive computation of the effect of the most damaging nsSNPs on both structure and function of bovine leptin Exploration of these mutations may provide novel perspectives for various production traits associated features Keywords bovine computational analysis leptin non synonymous SNPs Introduction One of the most prominent hormones that provide hotspot indicators for numerous metabolic traits of cattle is leptin Leptin is a hormone that regulates the body weight by maintaining the balance between food intake and energy expenditure through signaling to the brain to change the stored energy levels Zhou et al 2009 It plays a crucial role in the regulation of feed and energy metabolism of cattle Liefers et al 2005 In addition to the obvious role of leptin in controlling appetite it has other noticeable roles in regulating growth reproduction body composition and immunity Leptin is encoded by a LEP gene which is accommodated a size of about 20kb It consists of three exons separated by two introns and the exons for the LEP gene cover about 15kb of the bovine genome Actually the first exon is truncated in the mature blood circulating hormone Meanwhile the rest two exons produce the fully mature 167 residues by excising the first 24 signal amino acid residues to produce 16kd of blood circulating leptin Liefers 2004 Leptin contains a distinctive three dimensional 3 D four α helix bundle structure of A B C D pattern Kline et al 1997 This structure is arranged in a four sequentially similar anti parallel left hand twisted α helices bundle that are connected by two crossover links along with one short loop Gutierrez et al 2009 In addition to the four main helices an extra fragment that known as helix E which is a distorted short helix is also presented on the structure