Brabq2 was identified in animals hemizygous for Tg(APPSw)40Btla.
Mapping and Phenotype information for this QTL, its variants and associated markers
Linkage analysis was performed on 516 animals from a (B6.129-Tg(APPSw)40Btla x D2.129-Tg(APPSw)40Btla)F2 intercross to identify QTL associated with brain amyloid beta levels. Parental strain B6.129-Tg(APPSw)40Btla displays significantly higher levels of brain amyloid beta (20% more) by 28 days of age and develops amyloid plaques by 14 months of age whereas parental strain D2.129-Tg(APPSw)40Btla displays lower brain amyloid beta levels and do not develop amyloid plaques up to 24 months of age. F2 animals hemizygous for the transgene were sacrificed at 28 days of age and analyzed brain amyloid beta levels. A panel of 902 SNP markers was used for genome scan. The following QTLs each contribute approximately 4% of the phenotypic variance.
A locus at 182 Mbon mouse Chromosome 1 near rs13476273 showed suggestive association to brain amyloid beta levels with a LOD score of 3.127. This locus is named Brabq1 (brain amyloid beta QTL 1). DBA/2J-derived alleles at Brabq1 are protective and confer decreased levelsof brain amyloid beta with a partially dominant mode of inheritance. C57BL/6J-derived alleles appear to increase amyloid beta with a partially recessive mode of inheritance. The Brabq1 region is syntenic to human Chromosome 1q43-q44 which displays association with Alzheimer's disease in humans.
Significant linkage to brain amyloid beta levels mapped to 41.2 Mb on mouse Chromosome 2 near rs13476454 (LOD=4.89). This locus is named Brabq2 (brain amyloid beta QTL 2). DBA/2J-derived alleles at Brabq2 confer decreased levels of brain amyloid beta in a partially recessive manner while C57BL/6J-derived alleles confer increased beta amyloid levels in a partially dominant manner. Hc (23.5 cM) and Lrp1b (40.45 Mb) are potential candidate genes for Brabq2. The Brabq2 locus is syntenic with regions of human Chromosomes 9q33 and 2q22-q24 that have been associated with Alzheimer's disease.
Suggestive linkage to brain amyloid beta levels mapped to63.68 Mb on mouse Chromosome 7 near rs13479319 (LOD=3.69). This locus isnamed Brabq3 (brain amyloid beta QTL 3). DBA/2J-derived alleles at Brabq3 confer decreased brain amyloid beta levels with partially recessive inheritance while C57BL/6J-derived alleles confer increased brain amyloid beta with partially dominant inheritance. Apba2 at 25.5 cM is a potential candidate gene for Brabq3.
The Tg(APPSw)40Btla transgene mapped to mouse Chromosome 13 between rs3688207 (44.933Mb) and gnf.13.093.328 (88.907 Mb) using SNP analysis.