false
zh-CN,zh-TW,en,fr,de,ja,ko,pt,es,th,vi
Catalog
2023 ACMG Annual Clinical Genetics Meeting Digital ...
RNA-sequencing for Diagnosis and Novel Gene Discov ...
RNA-sequencing for Diagnosis and Novel Gene Discovery in Heritable Thoracic Aortic Aneurysms and Aortic Dissections (HTAD)
Back to course
Pdf Summary
This study focused on the use of RNA-sequencing to diagnose and discover novel genes associated with heritable thoracic aortic aneurysms and aortic dissections (HTAD). Despite extensive testing, only 30% of patients with a family history of HTAD have a known causative gene variant. The researchers used RNA-seq on skin fibroblasts from 15 unsolved HTAD cases and applied the DROP technique to detect outliers in splicing and expression. They annotated these outliers with OMIM data and other information to prioritize candidate genes.<br /><br />The results showed that RNA-seq identified splicing and expression outliers in the HTAD cohort, and skin fibroblasts were found to be a reasonable proxy for aortic smooth muscle cells in terms of gene expression profiles. The analysis also identified approximately three non-OMIM genes per sample with low expression and likely intolerant of loss-of-function mutations. Treatment with cycloheximide (CHX) significantly improved the ability to detect abnormal splicing by suppressing nonsense-mediated decay. Whole genome sequencing is pending to identify the likely non-coding causative variant.<br /><br />The study concluded that RNA-seq outlier analysis is a novel and innovative approach to identifying causative variants for HTAD. This method efficiently detects alterations in RNA expression and splicing in known HTAD genes, provides information for identifying causative genetic variants, and identifies potential novel disease genes for further investigation.<br /><br />The researchers also provided tables and figures illustrating notable findings, such as pseudoexons and changes in gene expression, in the HTAD cohort. The study emphasized the importance of identifying the genes predisposing to TAAD in order to prevent early deaths caused by thoracic aortic aneurysms and acute aortic dissections.
Asset Subtitle
Presenting Author - David R. Murdock, MD; Co-Author - Alana Cecchi, MS, CGC; Co-Author - Dongchuan Guo, PhD; Co-Author - Isabella C. Marin, RN, BSN; Co-Author - Xue-Yan Duan, PhD; Co-Author - Callie S. Kwartler, PhD; Co-Author - Dianna Milewicz, MD, PhD;
Meta Tag
Bioinformatics
Cardiovascular System
Genome sequencing
Sequencing
Variant Detection
Co-Author
Alana Cecchi, MS, CGC
Co-Author
Dongchuan Guo, PhD
Co-Author
Isabella C. Marin, RN, BSN
Co-Author
Xue-Yan Duan, PhD
Co-Author
Callie S. Kwartler, PhD
Co-Author
Dianna Milewicz, MD, PhD
Presenting Author
David R. Murdock, MD
Keywords
RNA-sequencing
HTAD
causative gene variant
skin fibroblasts
splicing
expression outliers
gene expression profiles
abnormal splicing
nonsense-mediated decay
TAAD
© 2025 American College of Medical Genetics and Genomics. All rights reserved.
×