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Whole Genome and Exome Sequencing of Monozygotic Twins with Trisomy 21, Discordant for a Congenital Heart Defect and Epilepsy
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Document Title
Whole Genome and Exome Sequencing of Monozygotic Twins with Trisomy 21, Discordant for a Congenital Heart Defect and Epilepsy
Author
Chaiyasap P, Kulawonganunchai S, Srichomthong C, Tongsima S, Suphapeetiporn K, Shotelersuk V
Name from Authors Collection
Affiliations
Chulalongkorn University; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); Chulalongkorn University; Chulalongkorn University
Type
Article
Source Title
PLOS ONE
ISSN
1932-6203
Year
2014
Volume
9
Issue
6
Page
-
Open Access
Green Published, Green Submitted, gold
Publisher
PUBLIC LIBRARY SCIENCE
DOI
10.1371/journal.pone.0100191
Format
Abstract
Congenital heart defects (CHD) occur in 40% of patients with trisomy 21, while the other 60% have a structurally normal heart. This suggests that the increased dosage of genes on chromosome 21 is a risk factor for abnormal heart development. Interaction of genes on chromosome 21 or their gene products with certain alleles of genes on other chromosomes could contribute to CHD. Here, we identified a pair of monozygotic twins with trisomy 21 but discordant for a ventricular septal defect and epilepsy. Twin-zygosity was confirmed by microsatellite genotyping. We hypothesized that some genetic differences from post-twinning mutations caused the discordant phenotypes. Thus, next generation sequencing (NGS) technologies were applied to sequence both whole genome and exome of their leukocytes. The post-analyses of the sequencing data revealed 21 putative discordant exonic variants between the twins from either genome or exome data. However, of the 15 variants chosen for validation with conventional Sanger sequencing, these candidate variants showed no differences in both twins. The fact that no discordant DNA variants were found suggests that sequence differences of DNA from leukocytes of monozygotic twins might be extremely rare. It also emphasizes the limitation of the current NGS technology in identifying causative genes for discordant phenotypes in monozygotic twins.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Funding Sponsor
Ratchadapiseksomphot Endowment Fund of Chulalongkorn University [RES560530177-HR]; Thailand Research Fund [RTA5680003, RSA5480022, RSA5480026]; Royal Golden Jubilee Ph.D. Program [PHD/0071/2552]; Research Chair Grants by the National Science and Technology Development Agency (NSTDA)
License
CC-BY
Rights
Authors
Publication Source
WOS