Using gene-history and expression analyses to assess the involvement of LGI genes in human disorders

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2005
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Gu, Wenli
Gibert, Yann
Wirth, Thierry
Elischer, Andrea
Bloch, Wilhelm
Steinlein, Ortrud K.
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Molecular Biology and Evolution. 2005, 22(11), pp. 2209-2216. ISSN 0737-4038. eISSN 1537-1719. Available under: doi: 10.1093/molbev/msi214
Zusammenfassung

Mutations in the leucine-rich, glioma-inactivated 1 gene, LGI1, cause autosomal-dominant lateral temporal lobe epilepsy via unknown mechanisms. LGI1 belongs to a subfamily of leucine-rich repeat genes comprising four members (LGI1 LGI4) in mammals. In this study, both comparative developmental as well as molecular evolutionary methods were applied to investigate the evolution of the LGI gene family and, subsequently, of the functional importance of its different gene members. Our phylogenetic studies suggest that LGI genes evolved early in the vertebrate lineage. Genetic and expression analyses of all five zebrafish lgi genes revealed duplications of lgi1 and lgi2, each resulting in two paralogous gene copies with mostly nonoverlapping expression patterns. Furthermore, all vertebrate LGI1 orthologs experience high levels of purifying selection that argue for an essential role of this gene in neural development or function. The approach of combining expression and selection data used here exemplarily demonstrates that in poorly characterized gene families a framework of evolutionary and expression analyses can identify those genes that are functionally most important and are therefore prime candidates for human disorders.

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570 Biowissenschaften, Biologie
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LGI1, zebrafish, epilepsy, phylogeny, expression pattern
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ISO 690GU, Wenli, Yann GIBERT, Thierry WIRTH, Andrea ELISCHER, Wilhelm BLOCH, Axel MEYER, Ortrud K. STEINLEIN, Gerrit BEGEMANN, 2005. Using gene-history and expression analyses to assess the involvement of LGI genes in human disorders. In: Molecular Biology and Evolution. 2005, 22(11), pp. 2209-2216. ISSN 0737-4038. eISSN 1537-1719. Available under: doi: 10.1093/molbev/msi214
BibTex
@article{Gu2005Using-7042,
  year={2005},
  doi={10.1093/molbev/msi214},
  title={Using gene-history and expression analyses to assess the involvement of LGI genes in human disorders},
  number={11},
  volume={22},
  issn={0737-4038},
  journal={Molecular Biology and Evolution},
  pages={2209--2216},
  author={Gu, Wenli and Gibert, Yann and Wirth, Thierry and Elischer, Andrea and Bloch, Wilhelm and Meyer, Axel and Steinlein, Ortrud K. and Begemann, Gerrit}
}
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    <dcterms:abstract xml:lang="eng">Mutations in the leucine-rich, glioma-inactivated 1 gene, LGI1, cause autosomal-dominant lateral temporal lobe epilepsy via unknown mechanisms. LGI1 belongs to a subfamily of leucine-rich repeat genes comprising four members (LGI1 LGI4) in mammals. In this study, both comparative developmental as well as molecular evolutionary methods were applied to investigate the evolution of the LGI gene family and, subsequently, of the functional importance of its different gene members. Our phylogenetic studies suggest that LGI genes evolved early in the vertebrate lineage. Genetic and expression analyses of all five zebrafish lgi genes revealed duplications of lgi1 and lgi2, each resulting in two paralogous gene copies with mostly nonoverlapping expression patterns. Furthermore, all vertebrate LGI1 orthologs experience high levels of purifying selection that argue for an essential role of this gene in neural development or function. The approach of combining expression and selection data used here exemplarily demonstrates that in poorly characterized gene families a framework of evolutionary and expression analyses can identify those genes that are functionally most important and are therefore prime candidates for human disorders.</dcterms:abstract>
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