Institute of Biomedical Sciences

Title

Platelet mRNA splicing landscape and its effect on platelet activity: An ACCOuNT Consortium Study

Document Type

Poster

Abstract Category

Basic Biomedical Sciences

Keywords

alternative splicing, platelets, racial disparities

Publication Date

Spring 5-1-2019

Abstract

Cardiovascular disease (CVD) is responsible for >630,000 deaths in the U.S. every year and is the leading cause of death both in the U.S. and worldwide. Aberrant platelet activity has been linked to an increased risk of CVD, including thrombosis, arteriosclerosis, stroke, heart attack and pulmonary embolism. Differences in platelet activity have been linked to polymorphisms in platelet-related genes, but little research has investigated the role of differential alternative splicing on platelet activity. Platelet RNA-Seq data from public repositories (i.e. Gene Expression Omnibus, N = 55) and diverse cohort of healthy volunteers (N = 25 of both European and African Americans) were analyzed to catalog mRNA splicing events. Analysis of public RNA-Seq data identified approximately 7,300 genes that were expressed in at least 75% of samples. These 7,300 genes were associated on average with 5 expressed variants per gene. Clusters of unique splicing patterns could be identified in small subsets of healthy volunteers. For example, isolated mRNA splicing patterns for the ARRB1, GP6, ITGB3 and TBXAS1 genes were identified in <5% of healthy volunteers. These unique splicing events portend protein isoforms leading to aberrant platelet activity and the functional consequences of these isolated splicing events are currently under investigation. We have also generated RNA-Seq data from the platelets of healthy African Americans (AAs) and European Americans (EAs) in order to define population-enriched or -specific splicing events (i.e. the Splicing Landscape). This approach has the potential to identify splice variant biomarkers of platelet dysfunction and CVD disparities that may be leveraged for the future development of therapies. In addition, a comparison of the splicing landscape in platelets from EA or AA was initiated to identify population specific splice variants. Preliminary analysis of the RNA-Seq data identified 225 genes exhibiting differential RNA splicing between the two populations. This study reveals that the mRNA splicing landscape varies between individuals, and these differences may affect platelet function and serve as biomarkers to identify CVD risk.

Open Access

1

Comments

Presented at Research Days 2019.

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Platelet mRNA splicing landscape and its effect on platelet activity: An ACCOuNT Consortium Study

Cardiovascular disease (CVD) is responsible for >630,000 deaths in the U.S. every year and is the leading cause of death both in the U.S. and worldwide. Aberrant platelet activity has been linked to an increased risk of CVD, including thrombosis, arteriosclerosis, stroke, heart attack and pulmonary embolism. Differences in platelet activity have been linked to polymorphisms in platelet-related genes, but little research has investigated the role of differential alternative splicing on platelet activity. Platelet RNA-Seq data from public repositories (i.e. Gene Expression Omnibus, N = 55) and diverse cohort of healthy volunteers (N = 25 of both European and African Americans) were analyzed to catalog mRNA splicing events. Analysis of public RNA-Seq data identified approximately 7,300 genes that were expressed in at least 75% of samples. These 7,300 genes were associated on average with 5 expressed variants per gene. Clusters of unique splicing patterns could be identified in small subsets of healthy volunteers. For example, isolated mRNA splicing patterns for the ARRB1, GP6, ITGB3 and TBXAS1 genes were identified in <5% of healthy volunteers. These unique splicing events portend protein isoforms leading to aberrant platelet activity and the functional consequences of these isolated splicing events are currently under investigation. We have also generated RNA-Seq data from the platelets of healthy African Americans (AAs) and European Americans (EAs) in order to define population-enriched or -specific splicing events (i.e. the Splicing Landscape). This approach has the potential to identify splice variant biomarkers of platelet dysfunction and CVD disparities that may be leveraged for the future development of therapies. In addition, a comparison of the splicing landscape in platelets from EA or AA was initiated to identify population specific splice variants. Preliminary analysis of the RNA-Seq data identified 225 genes exhibiting differential RNA splicing between the two populations. This study reveals that the mRNA splicing landscape varies between individuals, and these differences may affect platelet function and serve as biomarkers to identify CVD risk.