Conservation genetics of Mahogany Gliders and their complex evolutionary relationship with Squirrel Gliders
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PROVIDER: PRJEB86795 | ENA |
REPOSITORIES: ENA
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Project description:Embryonic gene expression is remarkably conserved across vertebrates as observed, for instance, in the developing hearts of chicken and mouse which diverged >300 million years ago. However, most cis regulatory elements (CREs) are highly divergent, which makes orthology tracing based on sequence similarity difficult, especially at larger evolutionary distances. Some evidence suggests functional conservation of CREs despite sequence divergence. However, it remains unclear how widespread such functional conservation might be.
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Project description: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. SUBMITTER_CITATION: 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
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Project description:Embryonic gene expression is remarkably conserved across vertebrates as observed, for instance, in the developing hearts of chicken and mouse which diverged >300 million years ago. However, most cis regulatory elements (CREs) are highly divergent, which makes orthology tracing based on sequence similarity difficult, especially at larger evolutionary distances. Some evidence suggests functional conservation of CREs despite sequence divergence. However, it remains unclear how widespread such functional conservation might be.
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Project description:Embryonic gene expression is remarkably conserved across vertebrates as observed, for instance, in the developing hearts of chicken and mouse which diverged >300 million years ago. However, most cis regulatory elements (CREs) are highly divergent, which makes orthology tracing based on sequence similarity difficult, especially at larger evolutionary distances. Some evidence suggests functional conservation of CREs despite sequence divergence. However, it remains unclear how widespread such functional conservation might be.
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Project description:This study examines the best way to teach genetics to family medicine residents. First year family medicine residents at the University of Toronto will be taught basic clinical genetics as well as a specific disease in genetics via 3 different educational methods. All participants will undergo an oral examination and written knowledge test 3 months after this education. Results between groups will be compared, and the best way to teach genetics to residents determined.
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Project description:Identification of the coding elements in the genome is a fundamental step to understanding the building blocks of living systems. Short peptides (< 100 aa) have emerged as important regulators of development and physiology, but their identification has been limited by their size. We have leveraged the periodicity of ribosome movement on the mRNA to define actively translated ORFs by ribosome footprinting. This approach identifies several hundred translated small ORFs in zebrafish and human. Computational prediction of small ORFs from codon conservation patterns corroborates and extends these findings and identifies conserved sequences in zebrafish and human, suggesting functional peptide products (micropeptides). These results identify micropeptide‐encoding genes in vertebrates, providing an entry point to define their function in vivo.
2014-04-04 | GSE53693 | GEO
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