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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993785/ https://www.ncbi.nlm.nih.gov/pubmed/33765058 http://dx.doi.org/10.1371/journal.pone.0249148 |
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author | Kinney, Nick Kang, Lin Bains, Harpal Lawson, Elizabeth Husain, Mesam Husain, Kumayl Sandhu, Inderjit Shin, Yongdeok Carter, Javan K. Anandakrishnan, Ramu Michalak, Pawel Garner, Harold |
author_facet | Kinney, Nick Kang, Lin Bains, Harpal Lawson, Elizabeth Husain, Mesam Husain, Kumayl Sandhu, Inderjit Shin, Yongdeok Carter, Javan K. Anandakrishnan, Ramu Michalak, Pawel Garner, Harold |
author_sort | Kinney, Nick |
collection | PubMed |
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 | Online Article Text |
id | pubmed-7993785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79937852021-04-05 Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans Kinney, Nick Kang, Lin Bains, Harpal Lawson, Elizabeth Husain, Mesam Husain, Kumayl Sandhu, Inderjit Shin, Yongdeok Carter, Javan K. Anandakrishnan, Ramu Michalak, Pawel Garner, Harold PLoS One Research Article 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. Public Library of Science 2021-03-25 /pmc/articles/PMC7993785/ /pubmed/33765058 http://dx.doi.org/10.1371/journal.pone.0249148 Text en © 2021 Kinney et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kinney, Nick Kang, Lin Bains, Harpal Lawson, Elizabeth Husain, Mesam Husain, Kumayl Sandhu, Inderjit Shin, Yongdeok Carter, Javan K. Anandakrishnan, Ramu Michalak, Pawel Garner, Harold Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans |
title | 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_short | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993785/ https://www.ncbi.nlm.nih.gov/pubmed/33765058 http://dx.doi.org/10.1371/journal.pone.0249148 |
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