The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot
Congenital heart defects (CHDs) are the most common birth defect in human with an incidence of almost 1% of all live births. Most cases have a multifactorial origin with both genetics and the environment playing a role in its development and progression. Adding an epigenetic component to this aspect...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Journal of Cardiovascular Development and Disease |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2308-3425/7/4/55 |
| _version_ | 1797545976501633024 |
|---|---|
| author | Marcel Grunert Sandra Appelt Paul Grossfeld Silke R. Sperling |
| author_facet | Marcel Grunert Sandra Appelt Paul Grossfeld Silke R. Sperling |
| author_sort | Marcel Grunert |
| collection | DOAJ |
| description | Congenital heart defects (CHDs) are the most common birth defect in human with an incidence of almost 1% of all live births. Most cases have a multifactorial origin with both genetics and the environment playing a role in its development and progression. Adding an epigenetic component to this aspect is exemplified by monozygotic twins which share the same genetic background but have a different disease status. As a result, the interplay between the genetic, epigenetic and the environmental conditions might contribute to the etiology and phenotype. To date, the underlying causes of the majority of CHDs remain poorly understood. In this study, we performed genome-wide high-throughput sequencing to examine the genetic, structural genomic and epigenetic differences of two identical twin pairs discordant for Tetralogy of Fallot (TOF), representing the most common cyanotic form of CHDs. Our results show the almost identical genetic and structural genomic identity of the twins. In contrast, several epigenetic alterations could be observed given by DNA methylation changes in regulatory regions of known cardiac-relevant genes. Overall, this study provides first insights into the impact of genetic and especially epigenetic factors underlying monozygotic twins discordant for CHD like TOF. |
| first_indexed | 2024-03-10T14:23:37Z |
| format | Article |
| id | doaj.art-b6c47bd4008142038e5b1d4a46caa9f6 |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-10T14:23:37Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-b6c47bd4008142038e5b1d4a46caa9f62023-11-20T23:14:04ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252020-12-01745510.3390/jcdd7040055The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of FallotMarcel Grunert0Sandra Appelt1Paul Grossfeld2Silke R. Sperling3Cardiovascular Genetics, Charité—Universitätsmedizin Berlin, 13125 Berlin, GermanyCardiovascular Genetics, Charité—Universitätsmedizin Berlin, 13125 Berlin, GermanyDivision of Cardiology, University of California San Diego, Rady’s Hospital MC 5004, San Diego, CA 92123, USACardiovascular Genetics, Charité—Universitätsmedizin Berlin, 13125 Berlin, GermanyCongenital heart defects (CHDs) are the most common birth defect in human with an incidence of almost 1% of all live births. Most cases have a multifactorial origin with both genetics and the environment playing a role in its development and progression. Adding an epigenetic component to this aspect is exemplified by monozygotic twins which share the same genetic background but have a different disease status. As a result, the interplay between the genetic, epigenetic and the environmental conditions might contribute to the etiology and phenotype. To date, the underlying causes of the majority of CHDs remain poorly understood. In this study, we performed genome-wide high-throughput sequencing to examine the genetic, structural genomic and epigenetic differences of two identical twin pairs discordant for Tetralogy of Fallot (TOF), representing the most common cyanotic form of CHDs. Our results show the almost identical genetic and structural genomic identity of the twins. In contrast, several epigenetic alterations could be observed given by DNA methylation changes in regulatory regions of known cardiac-relevant genes. Overall, this study provides first insights into the impact of genetic and especially epigenetic factors underlying monozygotic twins discordant for CHD like TOF.https://www.mdpi.com/2308-3425/7/4/55congenital heart diseaseTetralogy of Fallotmonozygotic twinsdiscordant phenotypegeneticsvariations |
| spellingShingle | Marcel Grunert Sandra Appelt Paul Grossfeld Silke R. Sperling The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot Journal of Cardiovascular Development and Disease congenital heart disease Tetralogy of Fallot monozygotic twins discordant phenotype genetics variations |
| title | The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot |
| title_full | The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot |
| title_fullStr | The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot |
| title_full_unstemmed | The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot |
| title_short | The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot |
| title_sort | needle in the haystack searching for genetic and epigenetic differences in monozygotic twins discordant for tetralogy of fallot |
| topic | congenital heart disease Tetralogy of Fallot monozygotic twins discordant phenotype genetics variations |
| url | https://www.mdpi.com/2308-3425/7/4/55 |
| work_keys_str_mv | AT marcelgrunert theneedleinthehaystacksearchingforgeneticandepigeneticdifferencesinmonozygotictwinsdiscordantfortetralogyoffallot AT sandraappelt theneedleinthehaystacksearchingforgeneticandepigeneticdifferencesinmonozygotictwinsdiscordantfortetralogyoffallot AT paulgrossfeld theneedleinthehaystacksearchingforgeneticandepigeneticdifferencesinmonozygotictwinsdiscordantfortetralogyoffallot AT silkersperling theneedleinthehaystacksearchingforgeneticandepigeneticdifferencesinmonozygotictwinsdiscordantfortetralogyoffallot AT marcelgrunert needleinthehaystacksearchingforgeneticandepigeneticdifferencesinmonozygotictwinsdiscordantfortetralogyoffallot AT sandraappelt needleinthehaystacksearchingforgeneticandepigeneticdifferencesinmonozygotictwinsdiscordantfortetralogyoffallot AT paulgrossfeld needleinthehaystacksearchingforgeneticandepigeneticdifferencesinmonozygotictwinsdiscordantfortetralogyoffallot AT silkersperling needleinthehaystacksearchingforgeneticandepigeneticdifferencesinmonozygotictwinsdiscordantfortetralogyoffallot |