Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.

Approximately three percent of the human genome is occupied by microsatellites: a type of short tandem repeat (STR). Microsatellites have well established effects on (a) the genetic structure of diverse human populations and (b) expression of nearby genes. These lines of inquiry have uncovered 3,984...

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Autores principales:	Nick Kinney, Lin Kang, Harpal Bains, Elizabeth Lawson, Mesam Husain, Kumayl Husain, Inderjit Sandhu, Yongdeok Shin, Javan K Carter, Ramu Anandakrishnan, Pawel Michalak, Harold Garner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4ba67c4616214ab08552862c3d7aa19d
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spelling	oai:doaj.org-article:4ba67c4616214ab08552862c3d7aa19d2021-11-25T06:19:25ZEthnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.1932-620310.1371/journal.pone.0249148https://doaj.org/article/4ba67c4616214ab08552862c3d7aa19d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0249148https://doaj.org/toc/1932-6203Approximately three percent of the human genome is occupied by microsatellites: a type of short tandem repeat (STR). Microsatellites have well established effects on (a) the genetic structure of diverse human populations and (b) expression of nearby genes. These lines of inquiry have uncovered 3,984 ethnically biased microsatellite loci (EBML) and 28,375 expression STRs (eSTRs), respectively. We hypothesize that a combination of EBML, eSTRs, and gene expression data (RNA-seq) can be used to show that microsatellites contribute to differential gene expression and phenotype in human populations. In fact, our previous study demonstrated a degree of mutual overlap between EBML and eSTRs but fell short of quantifying effects on gene expression. The present work aims to narrow the gap. First, we identify 313 overlapping EBML/eSTRs and recapitulate their mutual overlap. The 313 EBML/eSTRs are then characterized across ethnicity and tissue type. We use RNA-seq data to pursue validation of 49 regions that affect whole blood gene expression; 32 out of 54 affected genes are differentially expressed in Africans and Europeans. We quantify the relative contribution of these 32 genes to differential expression; fold change tends to be less than other differentially expressed genes. Repeat length correlates with expression for 15 of the 32 genes; two are conspicuously involved in glutathione metabolism. Finally, we repurpose a mathematical model of glutathione metabolism to investigate how a single polymorphic microsatellite affects phenotype. We conclude with a testable prediction that microsatellite polymorphisms affect GPX7 expression and oxidative stress in Africans and Europeans.Nick KinneyLin KangHarpal BainsElizabeth LawsonMesam HusainKumayl HusainInderjit SandhuYongdeok ShinJavan K CarterRamu AnandakrishnanPawel MichalakHarold GarnerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 3, p e0249148 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nick Kinney Lin Kang Harpal Bains Elizabeth Lawson Mesam Husain Kumayl Husain Inderjit Sandhu Yongdeok Shin Javan K Carter Ramu Anandakrishnan Pawel Michalak Harold Garner Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.
description	Approximately three percent of the human genome is occupied by microsatellites: a type of short tandem repeat (STR). Microsatellites have well established effects on (a) the genetic structure of diverse human populations and (b) expression of nearby genes. These lines of inquiry have uncovered 3,984 ethnically biased microsatellite loci (EBML) and 28,375 expression STRs (eSTRs), respectively. We hypothesize that a combination of EBML, eSTRs, and gene expression data (RNA-seq) can be used to show that microsatellites contribute to differential gene expression and phenotype in human populations. In fact, our previous study demonstrated a degree of mutual overlap between EBML and eSTRs but fell short of quantifying effects on gene expression. The present work aims to narrow the gap. First, we identify 313 overlapping EBML/eSTRs and recapitulate their mutual overlap. The 313 EBML/eSTRs are then characterized across ethnicity and tissue type. We use RNA-seq data to pursue validation of 49 regions that affect whole blood gene expression; 32 out of 54 affected genes are differentially expressed in Africans and Europeans. We quantify the relative contribution of these 32 genes to differential expression; fold change tends to be less than other differentially expressed genes. Repeat length correlates with expression for 15 of the 32 genes; two are conspicuously involved in glutathione metabolism. Finally, we repurpose a mathematical model of glutathione metabolism to investigate how a single polymorphic microsatellite affects phenotype. We conclude with a testable prediction that microsatellite polymorphisms affect GPX7 expression and oxidative stress in Africans and Europeans.
format	article
author	Nick Kinney Lin Kang Harpal Bains Elizabeth Lawson Mesam Husain Kumayl Husain Inderjit Sandhu Yongdeok Shin Javan K Carter Ramu Anandakrishnan Pawel Michalak Harold Garner
author_facet	Nick Kinney Lin Kang Harpal Bains Elizabeth Lawson Mesam Husain Kumayl Husain Inderjit Sandhu Yongdeok Shin Javan K Carter Ramu Anandakrishnan Pawel Michalak Harold Garner
author_sort	Nick Kinney
title	Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.
title_short	Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.
title_full	Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.
title_fullStr	Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.
title_full_unstemmed	Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.
title_sort	ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in africans and europeans.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4ba67c4616214ab08552862c3d7aa19d
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Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.

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