Minimal Strain Sets Explaining All Diagnostic Classes (Number of Markers Explained):
Solution 1: 129S4/SvJaeJ and C57BL/6J and C57BL/6NJ
C57BL/6J: 155 / 167 (92.8%)
129S4/SvJaeJ: 5 / 53 (9.4%)
C57BL/6NJ: 2 / 12 (16.7%)
Solution 2: 129S4/SvJaeJ and C57BL/6J and C57BL/6NTac
C57BL/6J: 155 / 167 (92.8%)
129S4/SvJaeJ: 5 / 53 (9.4%)
C57BL/6NTac: 2 / 12 (16.7%)
Solution 3: 129S4/SvJaeJ and C57BL/6J and C57BL/6NRj
C57BL/6J: 155 / 167 (92.8%)
129S4/SvJaeJ: 5 / 53 (9.4%)
C57BL/6NRj: 2 / 12 (16.7%)
Strain Reproducibility
Strain Reproducibility Samples: NA6730, WW1510
Inbreeding Level: 86.2%
Y Chromosome: Host
Congenicity Level: 88.4%
Donor Contribution in Linked Interval: 73.3Mb
The genome of this strain is not reproducible because there are regions that are still segregating (at least 13.8%) at the strain level.
The estimation of contribution of primary and secondary background depends on the number of samples genotyped.
The impact of this on the published phenotype(s) is unknown.
Notes
Genetic QC analysis (GQC) was performed on representative samples from the donor submission and provides a baseline reference. Regardless of the material ordered (live mice, sperm, embryos, resuscitated animals), the provided material is guaranteed to contain the primary genetic alteration of interest; however, the composition of the genetic background may vary (See Reproducibility sections of the report for details). The impact of genetic background on previously reported phenotypes has not been evaluated.
GQC analysis was done on two samples NA6730 (XX), WW1510 (XY) at the time of importation and the conclusions are consistent in both samples - both are not inbred and contain multiple C57BL/6 substrains. The results of the analysis are not congruent with the SDS (see special considerations and details below) and WW1510 is the representative sample selected for the report. The primary (host) background is C57BL/6J and there is positive evidence of C57BL/6J and C57BL/6N substrains. The secondary (donor) background is consistent with 129S4, which is indicated in the submission and the SDS as the donor strain (B6J/129S4 F1 ES Cells). The Y chromosome is consistent with at least one backcross to a male from the host background (C57BL/6J substrain). The mitochondrial genome is consistent with at least one backcross to a female from the host background (either the C57BL/6J or C57BL/6N substrain). The region containing the allele of interest has the 129S4 donor background. Therefore, the targeting event was on the 129S4 chromosome of the F1 ES cells. One sample is heterozygous and one sample is homozygous for the donor background at the locus. The following constructs are detected in both samples: hTK_Pr and r_FP.
The genome of the MMRRC: 43539 strain is 87.4% inbred and 89.6% congenic at the strain level. Donor contribution in the linked interval spans 73.3MB. The level of congenicity estimated by miniMUGA is inconsistent with the number of backcross generations reported in the SDS (8 generations). 71.2% of the genome is segregating for the two substrains (C57BL/6J and C57BL/6N) that contribute to the primary (host) background. The contribution of the C57BL/6J substrain is 59.3.X%. The contribution of the C57BL/6N substrain is 34%.
The estimated inbreeding, congenicity, and the relative strain/substrain contribution depend on the number of samples genotyped. The genomes of strains that are not fully inbred are not completely reproducible.
Special Considerations
Based on this report, a request has been made to update the strain name from B6J.Cg-Cdkn2atm4Nesh/Mmnc to B6(Cg)-Cdkn2atm4Nesh/Mmnc based on the presence of multiple C57BL/6 substrains and because the two samples genotyped do not support the level of inbreeding and consistency that would be expected for a congenic strain (February 6, 2024).
The samples contain an additional unknown background.
WARNINGS
There is a discrepancy between the diagnostic backgrounds detected ((129S4/SvJaeJ and C57BL/6J and C57BL/6NJ) or (129S4/SvJaeJ and C57BL/6J and C57BL/6NTac) or (129S4/SvJaeJ and C57BL/6J and C57BL/6NRj)) and the primary background (C57BL/6J) and secondary background (129S4/SvJaeJ). This is uncommon and should be investigated further.
This sample likely has more than 2 genetic backgrounds (unexplained regions and/or fractured ideogram). The strain selected for secondary background may be incorrect. The estimation of the contribution of primary and secondary background are likely incorrect. This can potentially be addressed with input from the user.