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G protein-coupled receptor genes in the FANTOM2 database
Yuka Kawasawa1, Louise M McKenzie, David P Hill
1Howard Hughes Medical Institute, Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9050, USA. Yuka.Kawasawa@UTSouthwestern.edu
Genome Research
|June 24, 2003
Summary
This study analyzed G protein-coupled receptor (GPCR) transcriptomes in mice, identifying new GPCR genes and numerous splicing variants. These findings highlight GPCR complexity and potential roles in disease.
Area of Science:
- Genomics and Molecular Biology
- Mammalian Receptor Research
- Transcriptome Analysis
Background:
- G protein-coupled receptors (GPCRs) are a vast family of mammalian proteins crucial for physiological and pathological processes.
- GPCR gene expression is tightly regulated in time and space, with alternative splicing contributing to functional diversity.
- Understanding GPCR transcriptome complexity is vital for deciphering their roles in health and disease.
Purpose of the Study:
- To comprehensively assess the complexity of the mammalian GPCR transcriptome.
- To identify novel GPCR genes and characterize their tissue distribution and alternative splicing patterns.
- To investigate the potential relevance of GPCR variants in disease pathogenesis.
Main Methods:
- Utilized the FANTOM2 project's extensive collection of full-length mouse cDNA.
- Clustered candidate GPCR cDNAs into transcriptional units (TUs).
- Analyzed tissue distribution patterns and alternative splicing events for identified GPCR transcripts.
Main Results:
- Identified 410 candidate GPCR cDNAs, reduced to 213 transcriptional units.
- Discovered 48 novel GPCR genes in mice, with 14 lacking clear mammalian orthologs.
- Revealed extensive alternative splicing in GPCRs, suggesting significant functional and regulatory diversity.
Conclusions:
- The mammalian GPCR repertoire is more complex than previously appreciated, with novel genes and extensive splicing variants.
- GPCR transcriptomic complexity, including alternative splicing, likely contributes to diverse biological functions and disease states.
- Challenges in cloning tissue-specific and low-abundance GPCR transcripts warrant further investigation.