Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans
| Autor: | Inderjit Sandhu, Kumayl Husain, Nicholas A. Kinney, Pawel Michalak, Elizabeth Lawson, Harold R. Garner, Lin Kang, Javan K. Carter, Harpal Bains, Ramu Anandakrishnan, Mesam Husain, Yongdeok Shin |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Physiology
Gene Expression Biochemistry GPX7 Geographical Locations Mathematical and Statistical Techniques Databases Genetic Gene expression Medicine and Health Sciences Ethnicities Genetics Principal Component Analysis Multidisciplinary Statistics Glutathione Phenotype Body Fluids Europe Blood Physical Sciences Microsatellite Medicine Anatomy Research Article Science Black People Genomics Biology Research and Analysis Methods White People Humans Statistical Methods Gene African People Glutathione Peroxidase Polymorphism Genetic Genome Human Biology and Life Sciences Cell Biology Fold change Oxidative Stress People and Places Multivariate Analysis Population Groupings Human genome Peptides Mathematics Microsatellite Repeats |
| Zdroj: | PLoS ONE, Vol 16, Iss 3, p e0249148 (2021) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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