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Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients
The contribution of low-frequency and damaging genetic variants associated with platelet function to ischemic stroke (IS) susceptibility remains unknown. We employed a deep re-sequencing approach in Polish patients in order to investigate the contribution of rare variants (minor allele frequency, MA...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751280/ https://www.ncbi.nlm.nih.gov/pubmed/29232918 http://dx.doi.org/10.3390/ijms18122678 |
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author | Janicki, Piotr K. Eyileten, Ceren Ruiz-Velasco, Victor Sedeek, Khaled Anwar Pordzik, Justyna Czlonkowska, Anna Kurkowska-Jastrzebska, Iwona Sugino, Shigekazu Imamura-Kawasawa, Yuka Mirowska-Guzel, Dagmara Postula, Marek |
author_facet | Janicki, Piotr K. Eyileten, Ceren Ruiz-Velasco, Victor Sedeek, Khaled Anwar Pordzik, Justyna Czlonkowska, Anna Kurkowska-Jastrzebska, Iwona Sugino, Shigekazu Imamura-Kawasawa, Yuka Mirowska-Guzel, Dagmara Postula, Marek |
author_sort | Janicki, Piotr K. |
collection | PubMed |
description | The contribution of low-frequency and damaging genetic variants associated with platelet function to ischemic stroke (IS) susceptibility remains unknown. We employed a deep re-sequencing approach in Polish patients in order to investigate the contribution of rare variants (minor allele frequency, MAF < 1%) to the IS genetic susceptibility in this population. The genes selected for re-sequencing consisted of 26 genes coding for proteins associated with the surface membrane of platelets. Targeted pooled re-sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of large-vessel IS) and 500 controls. After quality control and prioritization based on allele frequency and damaging probability, follow-up individual genotyping of deleterious rare variants was performed in patients from the original cohort. Gene-based analyses identified an association between IS and 6 rare functional and damaging variants in the purinergic genes (P2RY1 and P2RY12 locus). The predicted properties of the most damaging rare variants in P2RY1 and P2RY12 were confirmed by using mouse fibroblast cell cultures transfected with plasmid constructs containing cDNA of mutated variants (FLIPR on FlexStation3). This study identified a putative role for rare variants in P2RY1 and P2RY12 genes involved in platelet reactivity on large-vessel IS susceptibility in a Polish population. |
format | Online Article Text |
id | pubmed-5751280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57512802018-01-08 Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients Janicki, Piotr K. Eyileten, Ceren Ruiz-Velasco, Victor Sedeek, Khaled Anwar Pordzik, Justyna Czlonkowska, Anna Kurkowska-Jastrzebska, Iwona Sugino, Shigekazu Imamura-Kawasawa, Yuka Mirowska-Guzel, Dagmara Postula, Marek Int J Mol Sci Article The contribution of low-frequency and damaging genetic variants associated with platelet function to ischemic stroke (IS) susceptibility remains unknown. We employed a deep re-sequencing approach in Polish patients in order to investigate the contribution of rare variants (minor allele frequency, MAF < 1%) to the IS genetic susceptibility in this population. The genes selected for re-sequencing consisted of 26 genes coding for proteins associated with the surface membrane of platelets. Targeted pooled re-sequencing (Illumina HiSeq 2500) was performed on genomic DNA of 500 cases (patients with history of clinically proven diagnosis of large-vessel IS) and 500 controls. After quality control and prioritization based on allele frequency and damaging probability, follow-up individual genotyping of deleterious rare variants was performed in patients from the original cohort. Gene-based analyses identified an association between IS and 6 rare functional and damaging variants in the purinergic genes (P2RY1 and P2RY12 locus). The predicted properties of the most damaging rare variants in P2RY1 and P2RY12 were confirmed by using mouse fibroblast cell cultures transfected with plasmid constructs containing cDNA of mutated variants (FLIPR on FlexStation3). This study identified a putative role for rare variants in P2RY1 and P2RY12 genes involved in platelet reactivity on large-vessel IS susceptibility in a Polish population. MDPI 2017-12-11 /pmc/articles/PMC5751280/ /pubmed/29232918 http://dx.doi.org/10.3390/ijms18122678 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Janicki, Piotr K. Eyileten, Ceren Ruiz-Velasco, Victor Sedeek, Khaled Anwar Pordzik, Justyna Czlonkowska, Anna Kurkowska-Jastrzebska, Iwona Sugino, Shigekazu Imamura-Kawasawa, Yuka Mirowska-Guzel, Dagmara Postula, Marek Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients |
title | Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients |
title_full | Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients |
title_fullStr | Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients |
title_full_unstemmed | Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients |
title_short | Population-Specific Associations of Deleterious Rare Variants in Coding Region of P2RY1–P2RY12 Purinergic Receptor Genes in Large-Vessel Ischemic Stroke Patients |
title_sort | population-specific associations of deleterious rare variants in coding region of p2ry1–p2ry12 purinergic receptor genes in large-vessel ischemic stroke patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751280/ https://www.ncbi.nlm.nih.gov/pubmed/29232918 http://dx.doi.org/10.3390/ijms18122678 |
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