Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays

Abstract Single-nucleotide polymorphisms (SNPs) are the most common genetic variations for various complex human diseases, including cancers. Genome-wide association studies (GWAS) have identified numerous SNPs that increase cancer risks, such as breast cancer, colorectal cancer, and leukemia. These...

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Autores principales:	Nurul Ain Khoruddin, Mohd NurFakhruzzaman Noorizhab, Lay Kek Teh, Farida Zuraina Mohd Yusof, Mohd Zaki Salleh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e23e04dda3414f238cdfa542c76b0cab
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spelling	oai:doaj.org-article:e23e04dda3414f238cdfa542c76b0cab2021-12-02T18:50:47ZPathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays10.1038/s41598-021-95618-y2045-2322https://doaj.org/article/e23e04dda3414f238cdfa542c76b0cab2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95618-yhttps://doaj.org/toc/2045-2322Abstract Single-nucleotide polymorphisms (SNPs) are the most common genetic variations for various complex human diseases, including cancers. Genome-wide association studies (GWAS) have identified numerous SNPs that increase cancer risks, such as breast cancer, colorectal cancer, and leukemia. These SNPs were cataloged for scientific use. However, GWAS are often conducted on certain populations in which the Orang Asli and Malays were not included. Therefore, we have developed a bioinformatic pipeline to mine the whole-genome sequence databases of the Orang Asli and Malays to determine the presence of pathogenic SNPs that might increase the risks of cancers among them. Five different in silico tools, SIFT, PROVEAN, Poly-Phen-2, Condel, and PANTHER, were used to predict and assess the functional impacts of the SNPs. Out of the 80 cancer-related nsSNPs from the GWAS dataset, 52 nsSNPs were found among the Orang Asli and Malays. They were further analyzed using the bioinformatic pipeline to identify the pathogenic variants. Three nsSNPs; rs1126809 (TYR), rs10936600 (LRRC34), and rs757978 (FARP2), were found as the most damaging cancer pathogenic variants. These mutations alter the protein interface and change the allosteric sites of the respective proteins. As TYR, LRRC34, and FARP2 genes play important roles in numerous cellular processes such as cell proliferation, differentiation, growth, and cell survival; therefore, any impairment on the protein function could be involved in the development of cancer. rs1126809, rs10936600, and rs757978 are the important pathogenic variants that increase the risks of cancers among the Orang Asli and Malays. The roles and impacts of these variants in cancers will require further investigations using in vitro cancer models.Nurul Ain KhoruddinMohd NurFakhruzzaman NoorizhabLay Kek TehFarida Zuraina Mohd YusofMohd Zaki SallehNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nurul Ain Khoruddin Mohd NurFakhruzzaman Noorizhab Lay Kek Teh Farida Zuraina Mohd Yusof Mohd Zaki Salleh Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays
description	Abstract Single-nucleotide polymorphisms (SNPs) are the most common genetic variations for various complex human diseases, including cancers. Genome-wide association studies (GWAS) have identified numerous SNPs that increase cancer risks, such as breast cancer, colorectal cancer, and leukemia. These SNPs were cataloged for scientific use. However, GWAS are often conducted on certain populations in which the Orang Asli and Malays were not included. Therefore, we have developed a bioinformatic pipeline to mine the whole-genome sequence databases of the Orang Asli and Malays to determine the presence of pathogenic SNPs that might increase the risks of cancers among them. Five different in silico tools, SIFT, PROVEAN, Poly-Phen-2, Condel, and PANTHER, were used to predict and assess the functional impacts of the SNPs. Out of the 80 cancer-related nsSNPs from the GWAS dataset, 52 nsSNPs were found among the Orang Asli and Malays. They were further analyzed using the bioinformatic pipeline to identify the pathogenic variants. Three nsSNPs; rs1126809 (TYR), rs10936600 (LRRC34), and rs757978 (FARP2), were found as the most damaging cancer pathogenic variants. These mutations alter the protein interface and change the allosteric sites of the respective proteins. As TYR, LRRC34, and FARP2 genes play important roles in numerous cellular processes such as cell proliferation, differentiation, growth, and cell survival; therefore, any impairment on the protein function could be involved in the development of cancer. rs1126809, rs10936600, and rs757978 are the important pathogenic variants that increase the risks of cancers among the Orang Asli and Malays. The roles and impacts of these variants in cancers will require further investigations using in vitro cancer models.
format	article
author	Nurul Ain Khoruddin Mohd NurFakhruzzaman Noorizhab Lay Kek Teh Farida Zuraina Mohd Yusof Mohd Zaki Salleh
author_facet	Nurul Ain Khoruddin Mohd NurFakhruzzaman Noorizhab Lay Kek Teh Farida Zuraina Mohd Yusof Mohd Zaki Salleh
author_sort	Nurul Ain Khoruddin
title	Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays
title_short	Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays
title_full	Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays
title_fullStr	Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays
title_full_unstemmed	Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays
title_sort	pathogenic nssnps that increase the risks of cancers among the orang asli and malays
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e23e04dda3414f238cdfa542c76b0cab
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Pathogenic nsSNPs that increase the risks of cancers among the Orang Asli and Malays

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