Mapping the causal locus for maternal TRD in a family segregating for a copy-number variant at R2d2.

A) Pedigree of DO-G13–44xCC cross. Female DO-G13–44, mother of the G3 dams phenotyped for TR, is segregating for a copy-number variant at R2d2. G3 dams inheriting the maternal WSB/EiJ haplotype associated with the high-copy allele (R2d2^WSB) are colored black; those inheriting the WSB/EiJ haplotype associated with the low-copy allele (R2d2^WSBdel1) are colored red. Genotypes at marker chr2:85.65Mbp is denoted -/- (homozygous non-WSB), +/- (heterozygous WSB/EiJ) or +/+ (homozygous WSB/EiJ). ΔC_t, normalized cycle threshold by TaqMan qPCR assay; TR, transmission ratio, denoted as count of progeny inheriting a WSB/EiJ allele: count of progeny not inheriting a WSB allele; the paternal haplotype at chr2:83.6 Mb as determined by genotypes from the MegaMUGA array using the standard CC abbreviations is shown, A = A/J, E = NZO/HILtJ, ? = haplotype unknown. B) Distribution of ΔC_t values among 27 G3 dams. Points are colored as in panel A. C) TR among 27 G3 dams partitioned according to copy-number (CN) haplotype at R2d2. Points are colored as in panel A. D) QTL scan for TRD, treated as a binary phenotype, in 25 G3 dams genotyped with MegaMUGA. Only the maternal signal from Chr 2 is shown. Grey dashed line indicates threshold for significance at α = 0.01 obtained by unrestricted permutation. Candidate interval for R2d is shaded yellow. E) Empirical cumulative distribution of both maternal and paternal LOD scores genome-wide, with α = 0.01 significance threshold indicated by grey dashed line.