5 research outputs found
Transmission ratios in the progeny of <i>R2d2</i><sup><i>WSB/notWSB</i></sup> heterozygous F1 hybrid sires and dams.
<p>Transmission ratios in the progeny of <i>R2d2</i><sup><i>WSB/notWSB</i></sup> heterozygous F1 hybrid sires and dams.</p
<i>R2d</i> maps to a 9.3 Mb candidate interval.
<p>CC and DO mice were crossed to generate G1 dams, which were then crossed to FVB/NJ sires to determine the TR in their progeny. Each G1 dam carries a chromosome that is recombinant for the WSB/EiJ haplotype (shown under the heading <i>cis</i>) and a non-WSB/EiJ chromosome (the haplotype on the homologue is shown at far right under the heading <i>trans</i>). Dams with the same diplotype in the central region of Chr 2 were grouped together to define ten unique diplotypes. The aggregate number of WSB/EiJ and non-WSB/EiJ alleles transmitted by dams of each diplotype are shown for dams A) with TRD and B) without TRD. Significance of TR deviation from Mendelian expectation of 0.5 was computed using one-sided binomial exact test (<i>p</i>-value). The contribution from the eight founders of the CC and DO are shown in different colors. Thick purple bars indicate the extent of WSB/EiJ contributions, and thin bars indicate the extent of contributions from all other strains. The black box indicates the boundaries of the <i>R2d</i> candidate interval as determined by the region that is WSB/EiJ in all dams with TRD.</p
TRD at <i>R2d2</i> requires the combined action of meiotic drive and embryonic lethality.
<p>Relationship between maternal TR and average litter size (top panels) and average number of offspring inheriting alternative alleles at R2d2 (bottom panels) for A) DO G13 dams, B) DO G16 dams, C) G3 dams in the D0-G13–44 pedigree and D) (NZO/HILtJxWSB/EiJ)F1 dams. Top panels: gray circles are dams without TRD (A, B, D) or having the low-copy allele (C); blue circles are dams with TRD (A, B, D) or having the high-copy allele (C). For each point, bars show standard error for TR (horizontal) and average litter size (vertical). Dotted lines show mean litter sizes for each type of female. Red line shows a linear fit to TR and average litter size. Bottom panels: left and right pairs of boxplots show average number of offspring per litter in females without and with TRD (A, B, D) or having the low- and high-copy allele (C) that inherit a WSB/EiJ (purple) or non-WSB/EiJ (gray) allele. Females with a mutant <i>R2d2</i><sup><i>WSB</i></sup> allele are excluded. Note that there are significantly more WSB/EiJ offspring of dams with TRD in F1 hybrid dams than in DO without TRD.</p
Mapping the causal locus for maternal TRD in a family segregating for a copy-number variant at <i>R2d2</i>.
<p>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 <i>R2d2</i>. G3 dams inheriting the maternal WSB/EiJ haplotype associated with the high-copy allele (<i>R2d2</i><sup><i>WSB</i></sup>) are colored black; those inheriting the WSB/EiJ haplotype associated with the low-copy allele (<i>R2d2</i><sup><i>WSBdel1</i></sup>) are colored red. Genotypes at marker chr2:85.65Mbp is denoted -/- (homozygous non-WSB), +/- (heterozygous WSB/EiJ) or +/+ (homozygous WSB/EiJ). ΔC<sub>t</sub>, 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<sub>t</sub> 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 <i>R2d2</i>. 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 <i>α</i> = 0.01 obtained by unrestricted permutation. Candidate interval for <i>R2d</i> is shaded yellow. E) Empirical cumulative distribution of both maternal and paternal LOD scores genome-wide, with <i>α</i> = 0.01 significance threshold indicated by grey dashed line.</p
Linkage mapping localizes <i>R2d2</i> to a 900 kb region in Chr 2.
<p>A) Distribution of sum-intensity for the 34 probes in <i>R2d</i> present on the Mouse Diversity Array (MDA) for mice with a non-recombinant CAST/EiJ haplotype (green), a non-recombinant WSB/EiJ haplotype (purple) and non-CAST/EiJ/non-WSB/EiJ haplotypes (grey) is shown at the top of the panel. The sum intensity and recombinant haplotypes in six mice defining the boundaries of copy-number gain in the CAST/EiJ strain are shown below. B) Distribution of sum-intensity across three probes in <i>R2d</i> on the MegaMUGA array for mice with non-recombinant CAST/EiJ haplotype (green), a non-recombinant WSB/EiJ haplotype (purple) and non-CAST/EiJ/non-WSB/EiJ haplotypes (grey) is shown at the top of the panel. The sum intensity and recombinant haplotypes in six mice defining the boundaries of copy-number gain in the WSB/EiJ strain are shown below. C) QTL scan for the <i>R2d2</i> copy number gain using MDA sum-intensity as the phenotype in 330 CC G2:F<sub>1</sub> mice. D) QTL scan for the <i>R2d2</i> copy number gain using MegaMUGA sum-intensity as the phenotype in 96 (FVB/NJx(WSB/EiJxPWK/PhJ)F1)G2 offspring. E) Superposition of LOD curves from panels (C) and (D) on chromosome 2. The <i>R2d2</i> candidate interval is shaded in yellow.</p