Genome-wide linkage in mice.
One hundred and twenty DNA fragments were amplified across the genome, each selected to contain one or more strain-specific SNPs that would differentiate between C57BL/6J and 129x1/SvJ inbred strains [12]. Each fragment was initially amplified in 11 affected mice and nine unaffected mice; genotype calling was performed by dye-terminator sequencing of these fragments. Linkage analysis using these data was performed using mlink [13], which revealed a positive linkage at Chromosome 6qE1, on the 129x1/SvJ background (two-point LOD score 5.13 at marker 20.MMHAP85FLG2). In an attempt to narrow the disease interval we performed backcross experiments that resulted in the generation of three additional affected mice. Genotyping of all affected mice across the disease-segregating interval revealed flanking recombinants and a candidate region of ~5 Mb, between markers D6Mit37 and 44.MMHAP85FLG5 (Figure S1). This region contains 16 genes and predicted transcripts.