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Microarray‐assisted fine mapping of quantitative trait loci on chromosome 15 for susceptibility to seizure‐induced cell death in mice
Author(s) -
Schauwecker P. E.
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12351
Subject(s) - congenic , quantitative trait locus , biology , locus (genetics) , genetics , programmed cell death , candidate gene , phenotype , chromosome 4 , gene , microbiology and biotechnology , chromosome , apoptosis
Prior studies with crosses of the FVB / NJ ( FVB ; seizure‐induced cell death‐susceptible) mouse and the C 57 BL /6J ( B 6; seizure‐induced cell death‐resistant) mouse revealed the presence of a quantitative trait locus ( QTL ) on chromosome 15 that influenced susceptibility to kainic acid‐induced cell death ( S icd2 ). In an earlier study, we confirmed that the S icd2 interval harbors gene(s) conferring strong protection against seizure‐induced cell death through the creation of the FVB .B6‐ Sicd2 congenic strain, and created three interval‐specific congenic lines ( ISCL s) that encompass S icd2 on chromosome 15 to fine‐map this locus. To further localise this S icd2 QTL , an additional congenic line carrying overlapping intervals of the B 6 segment was created ( ISCL ‐4), and compared with the previously created ISCL ‐1– ISCL ‐3 and assessed for seizure‐induced cell death phenotype. Whereas all of the ISCL s showed reduced cell death associated with the B 6 phenotype, ISCL ‐4, showed the most extensive reduction in seizure‐induced cell death throughout all hippocampal subfields. In order to characterise the susceptibility loci on S icd2 by use of this ISCL and identify compelling candidate genes, we undertook an integrative genomic strategy of comparing exon transcript abundance in the hippocampus of this newly developed chromosome 15 subcongenic line ( ISCL ‐4) and FVB ‐like littermates. We identified 10 putative candidate genes that are alternatively spliced between the strains and may govern strain‐dependent differences in susceptibility to seizure‐induced excitotoxic cell death. These results illustrate the importance of identifying transcriptomics variants in expression studies, and implicate novel candidate genes conferring susceptibility to seizure‐induced cell death.