Rapid detection of gene mutations responsible for non-syndromic aortic aneurysm and dissection using two different methods: resequencing microarray technology and next-generation sequencing

Haruya Sakai; Shinichi Suzuki; Takeshi Mizuguchi; Kiyotaka Imoto; Yuki Yamashita; Hiroshi Doi; Masakazu Kikuchi; Yoshinori Tsurusaki; Hirotomo Saitsu; Noriko Miyake; Munetaka Masuda; Naomichi Matsumoto

doi:10.1007/s00439-011-1105-7

Rapid detection of gene mutations responsible for non-syndromic aortic aneurysm and dissection using two different methods: resequencing microarray technology and next-generation sequencing

Hum Genet. 2012 Apr;131(4):591-9. doi: 10.1007/s00439-011-1105-7. Epub 2011 Oct 15.

Authors

Haruya Sakai¹, Shinichi Suzuki, Takeshi Mizuguchi, Kiyotaka Imoto, Yuki Yamashita, Hiroshi Doi, Masakazu Kikuchi, Yoshinori Tsurusaki, Hirotomo Saitsu, Noriko Miyake, Munetaka Masuda, Naomichi Matsumoto

Affiliation

¹ Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan.

PMID: 22001912
DOI: 10.1007/s00439-011-1105-7

Abstract

Aortic aneurysm and/or dissection (AAD) is a life-threatening condition, and several syndromes are known to be related to AAD. In this study, two new technologies, resequencing array technology (ResAT) and next-generation sequencing (NGS), were used to analyze eight genes associated with syndromic AAD in 70 patients with non-syndromic AAD. Eighteen sequence variants were detected using both ResAT and NGS. In addition one of these sequence variants was detected by ResAT only and two additional variants by NGS only. Three of the 18 variants are likely to be pathogenic (in 4.3% of AAD patients and in 8.6% of a subset of patients with thoracic AAD), highlighting the importance of genetic analysis in non-syndromic AAD. ResAT and NGS similarly detected most, but not all, of the variants. Resequencing array technology was a rapid and efficient method for detecting most nucleotide substitutions, but was unable to detect short insertions/deletions, and it is impractical to update custom arrays frequently. Next-generation sequencing was able to detect almost all types of mutation, but requires improved informatics methods.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Adult
Aged
Aged, 80 and over
Amino Acid Sequence
Aortic Aneurysm / genetics*
Aortic Aneurysm, Thoracic / genetics
Aortic Dissection / genetics*
Collagen Type III / genetics
Female
Fibrillins
Genetic Predisposition to Disease / genetics*
Glucose Transport Proteins, Facilitative / genetics
Humans
Male
Microarray Analysis / methods
Microfilament Proteins / genetics
Middle Aged
Mutation*
Myosin Heavy Chains / genetics
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / genetics
Protein Serine-Threonine Kinases / genetics
Receptor, Transforming Growth Factor-beta Type I
Receptor, Transforming Growth Factor-beta Type II
Receptors, Transforming Growth Factor beta / genetics
Reproducibility of Results
Sequence Analysis, DNA / methods*
Sequence Homology, Amino Acid

Substances

ACTA2 protein, human
Actins
COL3A1 protein, human
Collagen Type III
Fibrillins
Glucose Transport Proteins, Facilitative
MYH11 protein, human
Microfilament Proteins
Receptors, Transforming Growth Factor beta
SLC2A10 protein, human
PLOD1 protein, human
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
Protein Serine-Threonine Kinases
Receptor, Transforming Growth Factor-beta Type I
Receptor, Transforming Growth Factor-beta Type II
Myosin Heavy Chains