<p>The superfamily of G protein-coupled receptors (GPCRs) is one of the largest protein families of mammalian genomes and can be divided into five main families; <i>Glutamate</i>, <i>Rhodopsin</i>, <i>Adhesion</i>, <i>Frizzled</i>, and <i>Secretin</i>. GPCRs participate in most major physiological functions, contributing to the fact that they are important targets in drug discovery. In paper I we mined the human and mouse genomes for new <i>Adhesion</i> GPCR genes. We found two new human genes (GPR133 and GPR144) and 17 mouse <i>Adhesion</i> genes, bringing the number up to 33 human and 31 mouse genes. In paper II we describe 53 new splice variants for human <i>Adhesion</i> receptors supported by expressed sequence tags (EST) data. 29 of these variants seem to code for functional proteins, several of which lack one or more functional domains in the N-termini. Lack of certain domains is likely to affect ligand binding or interaction with other proteins. Paper III describes the <i>Glutamate</i> GPCR in human, mouse, <i>Fugu</i>, and zebrafish. We gathered a total of 22 human, 79 mouse, 30 <i>Fugu</i>, and 32 zebrafish sequences and grouped these into eight clans using phylogenetic methods. The report provides an overview of the expansion or deletions among the different branches of the <i>Glutamate</i> receptor family. Paper IV focuses on the trace amine (TA) clan of <i>Rhodopsin</i> GPCRs. We identified 18 new rodent genes, 57 zebrafish genes, and eight <i>Fugu</i> genes belonging to the clan. Chromosomal mapping together with phylogenetic relationships suggests that the family arose through several mechanisms involving tetraploidisation, block duplications, and local duplication events. Paper V provides a comprehensive dataset of the GPCR superfamily of human and mouse containing 495 mouse and 400 human non-olfactory GPCRs. Phylogenetic analyses showed that 329 of the receptors are found in one-to-one orthologous pairs, whereas other receptors may have originated from species-specific expansions.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-6627 |
| Date | January 2006 |
| Creators | Bjarnadóttir, Þóra Kristín |
| Publisher | Uppsala University, Department of Neuroscience, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 121 |
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