Deakin University
Browse
gibert-usinggene-2005.pdf (484.07 kB)

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

Download (484.07 kB)
journal contribution
posted on 2005-01-01, 00:00 authored by W Gu, Y Gibert, T Wirth, A Elischer, W Bloch, A Meyer, O Steinlein, G Begemann
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.

History

Journal

Molecular biology and evolution

Volume

22

Pagination

2209 - 2216

Location

Oxford, Eng.

Open access

  • Yes

ISSN

0737-4038

eISSN

1537-1719

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Usage metrics

    Research Publications

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC