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Series GSE77799 Query DataSets for GSE77799
Status Public on Apr 13, 2017
Title The complex genetics of hypoplastic left heart syndrome
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Congenital heart disease (CHD) is a prevalent birth defect affecting up to 1% of live births. While a genetic etiology is indicated by increased recurrence risk and association with chromosomal abnormalities, the genetics of CHD is poorly understood and likely complex. Here we show hypoplastic left heart syndrome (HLHS), a severe CHD with high morbidity/mortality, has a multigenic etiology. Analysis of 8 HLHS mutant mouse lines recovered from a large-scale mutagenesis screen showed no mutations are shared in common. In the *Ohia* mouse line, mutations in 2 genes, *Pcdha9*/*Sap130*, act synergistically to cause HLHS. Cardiomyocyte proliferation and differentiation defects likely act in concert with valve abnormalities to cause HLHS. Network analysis of mutations recovered in HLHS mice and 68 HLHS patients point to Notch signaling disruption, a pathway previously implicated in HLHS. These findings demonstrate large-scale mutagenesis is an effective systems approach for interrogating the complex genetics of human diseases.

Journal: Nature Genetics
Title: The complex genetics of hypoplastic left heart syndrome
Author names: Xiaoqin Liu1, Hisato Yagi1, Shazina Saeed1, Abha S. Bais1, George C. Gabriel1, Zhaohan Chen1, Kevin A. Peterson4, You Li1, Molly C. Schwartz1, William T. Reynolds1, Manush Saydmohammed1, Brian Gibbs1, Yijen Wu1, William Devine1, Bishwanath Chatterjee1, Nikolai T. Klena1, Dennis Kostka1, Karen L. de Mesy Bentley5, Madhavi K.Ganapathiraju2, Phillip Dexheimer11, Linda Leatherbury7, Omar Khalifa1, Anchit Bhagat1, Maliha Zahid1, William Pu8, Simon Watkins3, Paul Grossfeld9, Stephen Murray4, George A. Porter, Jr.6, Michael Tsang1, Lisa J.Martin10, D.Woodrow.Benson12, Bruce J. Aronow11, Cecilia W. Lo1
Overall design Refer to individual Series
Citation(s) 28530678
Submission date Feb 10, 2016
Last update date May 15, 2019
Contact name Cecilia W Lo
Organization name University of Pittsburgh
Department Developmental Biology
Street address 530 45th St., 8120 Rangos Research Center
City Pittsburgh
State/province PA
ZIP/Postal code 15201
Country USA
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (18)
GSM2058466 Sap130_ChIPSeq
GSM2058467 Input DNA
GSM2059610 CTRL_635-260-2-LV
This SuperSeries is composed of the following SubSeries:
GSE77746 Sap130 ChIP-seq on Mouse E12.5 heart
GSE77798 Pathogenesis of Hypoplastic Left Heart Syndrome [RNA-seq]
BioProject PRJNA311577

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE77799_RAW.tar 591.0 Mb (http)(custom) TAR (of BED, TAR)
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