Successes and challenges of using whole exome sequencing to identify novel genes underlying an inherited predisposition for thoracic aortic aneurysms and acute aortic dissections

Trends in Cardiovascular Medicine
Dianna MilewiczDongchuan Guo


Thoracic aortic aneurysms involving the aortic root and/or ascending aorta can lead to acute aortic dissections. Approximately 20% of patients with thoracic aortic aneurysms and dissections (TAAD) have a family history of the disease, referred to as familial TAAD (FTAAD) that can be inherited in an autosomal dominant manner with variable expression with respect to disease presentation, age of onset and associated features. Whole exome sequencing (WES) has been used to identify causative mutations in novel genes for TAAD. The strategy used to reduce the large number of rare variants identified using WES is to sequence distant relatives with TAAD and filter for heterozygous rare variants that are shared between the relatives, predicted to disrupt protein function and segregate with the TAAD phenotype in other family members. Putative genes are validated by identifying additional families with a causative mutation in the genes. This approach has successfully identified novel genes for FTAAD.


Feb 9, 2016·American Journal of Medical Genetics. Part a·Jeffrey A SchubertStephanie M Ware
Feb 9, 2016·The Journal of Clinical Investigation·Shao-Qing KuangDianna Milewicz
Jul 21, 2015·The Annals of Thoracic Surgery·Bulat Ayratovich ZiganshinJohn Alex Elefteriades
Mar 31, 2015·The Journal of Pediatrics·Benjamin J LandisRobert B Hinton
Jan 10, 2016·Journal of the American Heart Association·Bulat Ayratovich ZiganshinJohn Alex Elefteriades
May 13, 2015·Circulation Research·Mara Martín-AlonsoAlicia G Arroyo
Jul 4, 2015·Circulation Research·Christina L PapkeHiromi Yanagisawa
Jul 22, 2016·European Journal of Clinical Investigation·Marina Gago-DíazMaría Brion
Jan 30, 2020·Biomolecules·Nicolai P OstbergJohn Alex Elefteriades
Sep 30, 2018·Biophysical Reviews·Stefanie S PortelliRichmond W Jeremy
Jun 1, 2019·Indian Journal of Thoracic and Cardiovascular Surgery : Official Organ, Association of Thoracic and Cardiovascular Surgeons of India·Adam Joseph BrownsteinJohn Alex Elefteriades


Aug 9, 1996·The Journal of Biological Chemistry·D P ReinhardtL Y Sakai
Dec 1, 1996·Circulation·Dianna MilewiczA Biddinger
Mar 1, 1997·Journal of Vascular Surgery·A BiddingerDianna Milewicz
Apr 13, 1999·Archives of Surgery·Michael A CoadyJohn Alex Elefteriades
Jan 10, 2003·Nucleic Acids Research·D KarolchikUniversity of California Santa Cruz
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Eiji IsotaniJames T Stull
May 5, 2004·Genome Research·James StalkerAntony V Cox
Jul 6, 2004·Nature Genetics·Takeshi MizuguchiNaomichi Matsumoto
Feb 8, 2006·Annual Review of Physiology·Karnam S Murthy
Sep 26, 2006·The Annals of Thoracic Surgery·Gonzalo AlbornozJohn Alex Elefteriades
Aug 7, 2007·American Journal of Medical Genetics. Part a·Melissa L LoscalzoHarry C Dietz
Jun 12, 2008·Annual Review of Genomics and Human Genetics·Dianna MilewiczHariyadarshi Pannu
Apr 8, 2009·The Journal of Biological Chemistry·Hai-Lei DingKristine E Kamm
Apr 8, 2009·Nature Methods·Emily H TurnerJay Shendure
Jan 11, 2011·Nature Genetics·Ingrid M B H van de LaarAida M Bertoli-Avella
Jun 24, 2011·PLoS Genetics·Shao-Qing KuangGenTAC Investigators
Aug 5, 2011·American Journal of Medical Genetics. Part a·Ellen S RegaladoDianna Milewicz
Sep 29, 2011·Nature Biotechnology·Michael J ClarkMichael Snyder
May 16, 2012·Genome Research·Niklas KrummEvan E Eichler
Aug 28, 2012·Trends in Cardiovascular Medicine·Ali J Marian
Oct 9, 2012·American Journal of Human Genetics·Menachem FromerShaun M Purcell
Aug 6, 2013·American Journal of Human Genetics·Dongchuan GuoDianna Milewicz

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