ZFIN ID: ZDB-PUB-050718-5
Using Gene-History and Expression Analyses to Assess the Involvement of LGI Genes in Human Disorders
Gu, W., Gibert, Y., Wirth, T., Elischer, A., Bloch, W., Meyer, A., Steinlein, O.K., and Begemann, G.
Date: 2005
Source: Mol. Biol. Evol.   22(11): 2209-2216 (Journal)
Registered Authors: Begemann, Gerrit, Gibert, Yann, Meyer, Axel
Keywords: LGI1, zebrafish, epilepsy, phylogeny, expression pattern, purifying selection
MeSH Terms:
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Epilepsy/genetics*
  • Evolution, Molecular*
  • Gene Expression*
  • Genes, Duplicate/genetics
  • Humans
  • In Situ Hybridization
  • Likelihood Functions
  • Models, Genetic
  • Molecular Sequence Data
  • Multigene Family/genetics*
  • Phylogeny*
  • Proteins/genetics*
  • Selection, Genetic
  • Sequence Analysis, DNA
  • Zebrafish/genetics
PubMed: 16014869 Full text @ Mol. Biol. Evol.
Mutations in the leucine-rich, glioma-inactivated 1 gene, LGI1, cause autosomal-dominant lateral temporal lobe epilepsy (ADLTE) via unknown mechanisms. LGI1 belongs to a subfamily of leucine-rich repeat genes comprised of 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 lgi1and lgi2, each resulting in two paralogous gene copies with mostly non-overlapping 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.