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

Gu, Wenli, Gibert, Yann, Wirth, Thierry, Elischer, Andrea, Bloch, Wilhelm, Meyer, Alex, Steinlein, Ortrud K. and Begemann, Gerrit 2005, Using gene-history and expression analyses to assess the involvement of LGI genes in human disorders, Molecular biology and evolution, vol. 22, no. 11, pp. 2209-2216, doi: 10.1093/molbev/msi214.

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Title Using gene-history and expression analyses to assess the involvement of LGI genes in human disorders
Author(s) Gu, Wenli
Gibert, Yann
Wirth, Thierry
Elischer, Andrea
Bloch, Wilhelm
Meyer, Alex
Steinlein, Ortrud K.
Begemann, Gerrit
Journal name Molecular biology and evolution
Volume number 22
Issue number 11
Start page 2209
End page 2216
Total pages 8
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2005
ISSN 0737-4038
1537-1719
Keyword(s) LGI1
zebrafish
epilepsy
phylogeny
expression pattern
purifying selection
Summary 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.
Language eng
DOI 10.1093/molbev/msi214
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30063551

Document type: Journal Article
Collection: School of Medicine
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