Experiment
Linkage analysis was performed on 32 BXD (B=C57BL/6J; D=DBA/2J) recombinant inbred (RI) strains to identify QTLs associated with hippocampal architecture. The hippocampal volume and body weight of parental strain C57BL/6J is greater compared to the hippocampal volume of DBA/2J. 623 polymorphic loci were analyzed.
Previously identified hippocampus volume QTLs Hipp1 and Hipp2 on mouse Chromosome 1 (89 cM) and mouse chromosome 5 (20 cM), respectively, overlap with suggestive loci detected in this study. The Hipp1 locus overlaps with a locus suggestively linked to pyramidal cell layer volume (LRS=11.1). This interval spans 62 cM - 91 cM. Rxrg is an interesting candidate found in this region.
Grv (granule cell layer volume), mapped to 19 cM on mouse Chromosome 6 with LRS=17.5 near D6Mit207. This locus was identified when Hipp3 was held constant. The QTL interval of Grv spans 7 cM - 30 cM. Hoxa4, Hoxa5, and Npy map to this interval and may be possible candidate genes.
Hipp3 mapped to 31 cM on mouse Chromosome 13. This locus is associated with dentate gyrus volume and exhibits additive inheritance. Hipp3 has a maximum LRS=17.7 near D13Mit94. The QTL interval of Hipp3 spans 26 cM - 45 cM. A strong interaction was observed between Hipp3 and a locus on mouse Chromosome 11 near D11Mit78 (2 cM), which is designated Hipp5. Animals homozygous for C57BL/6J-derived alleles at both Hipp3 and Hipp5 display significantly increased dentate gyrus volume compared to animals of other genotypes.
Hipp4 shows linkage to hippocampal volume and mapped to mouse Chromosome 15 with LRS=15.1. This locus has an additive effect. The Hipp4 interval spans 0 cM to 21 cM. Gdnf and Ghr map to this interval and are possible candidate genes for Hipp4.
Suggestive body weight QTLs mapped to mouse chromosomes 7, 11, and 16. The chromosome 11 body weight QTL does not overlap with the Grv. Suggestive brain weight QTLs mapped to mouse Chromosomes 15, 16, and 19.
Analysis Tools