Transcriptional Impact of Rare and Private Copy Number Variants in Hypoplastic Left Heart Syndrome
© 2015 Wiley Periodicals, Inc..
BACKGROUND: Hypoplastic left heart syndrome (HLHS) is a heterogeneous, lethal combination of congenital malformations characterized by severe underdevelopment of left heart structures, resulting in a univentricular circulation. The genetic determinants of this disorder are largely unknown. Evidence of copy number variants (CNVs) contributing to the genetic etiology of HLHS and other congenital heart defects has been mounting. However, the functional effects of such CNVs have not been examined, particularly in cases where the variant of interest is found in only a single patient.
METHODS AND RESULTS: Whole-genome SNP microarrays were employed to detect CNVs in two patient cohorts (N = 70 total) predominantly diagnosed with some form of nonsyndromic HLHS. We discovered 16 rare or private variants adjacent to or overlapping 20 genes associated with cardiovascular or premature lethality phenotypes in mouse knockout models. We evaluated the impact of selected variants on the expression of nine of these genes through quantitative PCR on cDNA derived from patient heart tissue. Four genes displayed significantly altered expression in patients with an overlapping or proximal CNV verses patients without such CNVs.
CONCLUSION: Rare and private genomic imbalances perturb transcription of genes that potentially affect cardiogenesis in a subset of nonsyndromic HLHS patients.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2015 |
|---|---|
| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Clinical and translational science - 8(2015), 6 vom: 03. Dez., Seite 682-9 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Glidewell, Steven C [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Cardiovascular diseases |
|---|
| Anmerkungen: |
Date Completed 14.10.2016 Date Revised 13.11.2018 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/cts.12340 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM254309518 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM254309518 | ||
| 003 | DE-627 | ||
| 005 | 20231224172110.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/cts.12340 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0847.xml |
| 035 | |a (DE-627)NLM254309518 | ||
| 035 | |a (NLM)26534787 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Glidewell, Steven C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Transcriptional Impact of Rare and Private Copy Number Variants in Hypoplastic Left Heart Syndrome |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 14.10.2016 | ||
| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2015 Wiley Periodicals, Inc. | ||
| 520 | |a BACKGROUND: Hypoplastic left heart syndrome (HLHS) is a heterogeneous, lethal combination of congenital malformations characterized by severe underdevelopment of left heart structures, resulting in a univentricular circulation. The genetic determinants of this disorder are largely unknown. Evidence of copy number variants (CNVs) contributing to the genetic etiology of HLHS and other congenital heart defects has been mounting. However, the functional effects of such CNVs have not been examined, particularly in cases where the variant of interest is found in only a single patient | ||
| 520 | |a METHODS AND RESULTS: Whole-genome SNP microarrays were employed to detect CNVs in two patient cohorts (N = 70 total) predominantly diagnosed with some form of nonsyndromic HLHS. We discovered 16 rare or private variants adjacent to or overlapping 20 genes associated with cardiovascular or premature lethality phenotypes in mouse knockout models. We evaluated the impact of selected variants on the expression of nine of these genes through quantitative PCR on cDNA derived from patient heart tissue. Four genes displayed significantly altered expression in patients with an overlapping or proximal CNV verses patients without such CNVs | ||
| 520 | |a CONCLUSION: Rare and private genomic imbalances perturb transcription of genes that potentially affect cardiogenesis in a subset of nonsyndromic HLHS patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a cardiovascular diseases | |
| 650 | 4 | |a congenital | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a heart defects | |
| 650 | 7 | |a DNA, Complementary |2 NLM | |
| 700 | 1 | |a Miyamoto, Shelley D |e verfasserin |4 aut | |
| 700 | 1 | |a Grossfeld, Paul D |e verfasserin |4 aut | |
| 700 | 1 | |a Clouthier, David E |e verfasserin |4 aut | |
| 700 | 1 | |a Coldren, Christopher D |e verfasserin |4 aut | |
| 700 | 1 | |a Stearman, Robert S |e verfasserin |4 aut | |
| 700 | 1 | |a Geraci, Mark W |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical and translational science |d 2008 |g 8(2015), 6 vom: 03. Dez., Seite 682-9 |w (DE-627)NLM186388268 |x 1752-8062 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2015 |g number:6 |g day:03 |g month:12 |g pages:682-9 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/cts.12340 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2015 |e 6 |b 03 |c 12 |h 682-9 | ||