Prdm9^dom2
QTL Variant Detail

Summary

• QTL variant: Prdm9^dom2
• Name: PR domain containing 9; Mus musculus domesticus 2
• MGI ID: MGI:5311020
• Synonyms: Prdm9^b
• QTL: Prdm9 Location: Chr17:15763341-15784616 bp, - strand Genetic Position: Chr17, 8.95 cM

Variant origin

• Strain of Specimen: multiple strains

Variant description

• Allele Type: QTL
• Mutation: Not Applicable
• Mutation details: Strains C57BL/6, C57BL/10, 129S1/SvImJ, A/J, AKR/J, BALB/cByJ, DBA/2J, FVB/NJ, KK/HiJ, NZO/HlLtJ and B10.A exhibit a polymorphism such that the protein product contains 12 zinc fingers compared to the 11, 13, or 14 observed in the protein product of other strains. (J:180577)

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:166751

In the present study a cytological assay of recombination in mouse pachytene spermatocytes was combined with QTL analyses to identify loci that contributed to genome-wide levels of recombination in male meiosis.

Specifically markers of crossovers, MLH1 foci, in 194 (C57BL/6J x CAST/EiJ)F2 male mice were analyzed. MLH1 is a DNA mismatch repair protein known to load onto pachytene-stage synaptonemal complexes at sites of crossovers. A remarkable variation in mean MLH1 (crossover) counts per spermatocyte was identified, with an approximate 15% difference between low CAST/EiJ (CAST) and high C57BL/6J (B6) recombination inbred strains of mice.

F2 male offspring were used for cytological analysis at 6-8 weeks of age. Surface spread preparations from testicular samples were made and the slides were immunostained with MLH1 and SYCP3 antibodies, respectively. Tail snips were collected from each of the F2 males. In initial analyses, mean MLH1 values were compared among B6, CAST, F1, and F2 animals (Fig. 1). However, for the subsequent QTL analyses the square root of the average number of MLH1 foci per cell was used as the phenotypic variable.

Ultimately multiple-QTL analyses using the stepwise selection algorithm were performed. QTL analyses were performed with R/qtl and add-on package for the general statistical software R (http://www.r-project.org). The fit and exploration of multiple-QTL models con- firmed the associations from initial genome scans to chromosomes 2, 3, 4, 14, 15, and X identified using the standard approach, and also indicated a significant association with a locus on chromosome 17.

Table 1:

QTL Recrq1 (recombination rate in male meiosis QTL 1) mapped to Chromosome 2 peaking at 72.6 cM with a LOD score of 6.31. The QTL spanned a 1.5 LOD support interval from 62.2 to 83.3 cM. The CAST allele was associated with higher recombination rates at Recrq1.

QTL Recrq2 (recombination rate in male meiosis QTL 2) mapped to Chromosome 3 peaking at 53.7 cM with a LOD score of 5.93. The QTL spanned a 1.5 LOD support interval from 45.8 to 58.8 cM. The B6 allele was associated with higher recombination rates at Recrq2.

QTL Recrq3 (recombination rate in male meiosis QTL 3) mapped to Chromosome 4 peaking at 45.0 cM with a LOD score of 4.98. The QTL spanned a 1.5 LOD support interval from 21.6 to 51.9 cM. The B6 allele was associated with higher recombination rates at Recrq3.

QTL Recrq4 (recombination rate in male meiosis QTL 4) mapped to Chromosome 14 peaking at 38.7 cM with a LOD score of 6.30. The QTL spanned a 1.5 LOD support interval from 32.7 to 45.7 cM. The CAST allele was associated with higher recombination rates at Recrq4.

QTL Recrq5 (recombination rate in male meiosis QTL 5) mapped to Chromosome 15 peaking at 22.6 cM with a LOD score of 3.86. The QTL spanned a 1.5 LOD support interval from 14.2 to 33.2 cM. The B6 allele was associated with higher recombination rates at Recrq5.

QTL Recrq6 (recombination rate in male meiosis QTL 6) mapped to Chromosome 17 peaking at 30.4 cM with a LOD score of 4.24. The QTL spanned a 1.5 LOD support interval from 25.4 to 42.2 cM. The B6 allele was associated with higher recombination rates at Recrq6.

QTL Recrq7 (recombination rate in male meiosis QTL 7) mapped to Chromosome X peaking at 55.6 cM with a LOD score of 7.75. The QTL spanned a 1.5 LOD support interval from 47.4 to 70.6 cM. The CAST allele was associated with higher recombination rates at Recrq7.

The Prdm9 locus on chromosome 17 is located just proximal to the 17-cM interval that was identified for Recrq6 QTL. Nevertheless, its strong effect on hotspot utilization prompted whether it might be responsible for some of the variation between CAST and B6 males. Allelic variation in Prdm9 was correlated with genome-wide MLH1 levels in the 194 F2 animals but no obvious effects were detected; indeed, the mean MLH1 values for animals with B6/B6, B6/CAST, or CAST/CAST genotypes were virtually identical to one another (data not shown).

References

• Original: J:180577 Grey C, et al., Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination. PLoS Biol. 2011 Oct;9(10):e1001176
• All: 8 reference(s)