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A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene

Leptin is a polypeptide hormone produced in the adipose tissue and governs many processes in the body. Recently, polymorphisms in the LEP gene revealed a significant change in body weight regulation, energy balance, food intake, and reproductive hormone secretion. This study considers its crucial ro...

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Autores principales: Girmay, Shishay, Ahmad, Hafiz Ishfaq, Zahra, Quratul Ain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377880/
https://www.ncbi.nlm.nih.gov/pubmed/35978633
http://dx.doi.org/10.1155/2022/7736485
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author Girmay, Shishay
Ahmad, Hafiz Ishfaq
Zahra, Quratul Ain
author_facet Girmay, Shishay
Ahmad, Hafiz Ishfaq
Zahra, Quratul Ain
author_sort Girmay, Shishay
collection PubMed
description Leptin is a polypeptide hormone produced in the adipose tissue and governs many processes in the body. Recently, polymorphisms in the LEP gene revealed a significant change in body weight regulation, energy balance, food intake, and reproductive hormone secretion. This study considers its crucial role in the regulation of the economically important traits of sheep. Several computational tools, including SIFT, Predict SNP2, SNAP2, and PROVEAN, have been used to screen out the deleterious nsSNPs. Following the screening of 11 nsSNPs in the sheep genome, 5 nsSNPs, T86M (C → T), D98N (G → A), N136T (A → C), R142Q (G → A), and P157Q (C → A), were predicted to have a significant deleterious effect on the LEP protein function, leading to phenotypic difference. The analysis of proteins' stability change due to amino acid substitution using the I-stable, SDM, and DynaMut consistently confirmed that three nsSNPs (T86M (C → T), D98N (G → A), and P157Q (C → A)) increased protein stability. It is suggested that these three nsSNPs may enhance the evolvability of LEP protein, which is vital for the evolutionary adaptation of sheep. Our findings demonstrate that the five nsSNPs reported in this study might be responsible for sheep's structural and functional modifications of LEP protein. This is the first comprehensive report on the sheep LEP gene. It narrow downs the candidate nsSNPs for in vitro experiments to facilitate the development of reliable molecular markers for associated traits.
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spelling pubmed-93778802022-08-16 A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene Girmay, Shishay Ahmad, Hafiz Ishfaq Zahra, Quratul Ain Biomed Res Int Research Article Leptin is a polypeptide hormone produced in the adipose tissue and governs many processes in the body. Recently, polymorphisms in the LEP gene revealed a significant change in body weight regulation, energy balance, food intake, and reproductive hormone secretion. This study considers its crucial role in the regulation of the economically important traits of sheep. Several computational tools, including SIFT, Predict SNP2, SNAP2, and PROVEAN, have been used to screen out the deleterious nsSNPs. Following the screening of 11 nsSNPs in the sheep genome, 5 nsSNPs, T86M (C → T), D98N (G → A), N136T (A → C), R142Q (G → A), and P157Q (C → A), were predicted to have a significant deleterious effect on the LEP protein function, leading to phenotypic difference. The analysis of proteins' stability change due to amino acid substitution using the I-stable, SDM, and DynaMut consistently confirmed that three nsSNPs (T86M (C → T), D98N (G → A), and P157Q (C → A)) increased protein stability. It is suggested that these three nsSNPs may enhance the evolvability of LEP protein, which is vital for the evolutionary adaptation of sheep. Our findings demonstrate that the five nsSNPs reported in this study might be responsible for sheep's structural and functional modifications of LEP protein. This is the first comprehensive report on the sheep LEP gene. It narrow downs the candidate nsSNPs for in vitro experiments to facilitate the development of reliable molecular markers for associated traits. Hindawi 2022-08-08 /pmc/articles/PMC9377880/ /pubmed/35978633 http://dx.doi.org/10.1155/2022/7736485 Text en Copyright © 2022 Shishay Girmay et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Girmay, Shishay
Ahmad, Hafiz Ishfaq
Zahra, Quratul Ain
A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene
title A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene
title_full A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene
title_fullStr A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene
title_full_unstemmed A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene
title_short A Simulation Analysis and Screening of Deleterious Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Sheep LEP Gene
title_sort simulation analysis and screening of deleterious nonsynonymous single nucleotide polymorphisms (nssnps) in sheep lep gene
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377880/
https://www.ncbi.nlm.nih.gov/pubmed/35978633
http://dx.doi.org/10.1155/2022/7736485
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