GENOME AND EXOME SEQUENCES OF MONOZYGOTIC TWINS WITH TRISOMY 21, DISCORDANT FOR A CONGENITAL HEART DEFECT

Abstract

Congenital heart defects (CHD) occur around 40% of individual with trisomy 21 while the remaining 60% have a structurally normal heart. This suggests that the extra copy of genes on chromosome 21 is a risk factor for abnormal heart development. Increased dosage of genes on chromosome 21 could interact with certain alleles of genes on other chromosomes and might contribute to CHD. Here, we identified a pair of Thai monozygotic twins with trisomy 21 but discordant for congenital heart defects. Twin-zygosity was confirmed to be monozygotic by microsatellite genotyping. We hypothesized that the discordant phenotype in these monozygotic twins could be resulted from post-twining mutation. Therefore, we applied next generation sequencing (NGS) technologies to sequence both genome and exome from their leukocytes DNA. The post-analysis of the sequencing data identified 15 discordant exonic variants between the twins. However, validation of all variants with conventional Sanger sequencing revealed no differences between both twins. Given that no discordant variants were found suggests that sequence differences of leukocytes’ DNA of monozygotic twins might be extremely rare. This also suggests the limitation of the current NGS technology in identifying causative genes for discordant phenotypes in monozygotic twins.