Table 1.
List of significant QTLs in Pre-CC, CC-RIX, CC011xCC074-F2, and CC003xCC053-F2.
| QTL ID | Population | Chromosome [Mb] | Phenotype(s) (days post infection- dpi) | Haplotype(s)+ | phenotypic variation [%] |
|---|---|---|---|---|---|
| Pre-CC (Gralinski et al., 2015) | |||||
| HrS1 | Pre-CC | chr3:18.3–26.8 | Perivascular cuffing (4dpi) | BH/ACDEFG | 26 % |
| HrS2 | Pre-CC | chr16:31.5–36.7 | Viral titer (4dpi) | G/ABCDEFH | 22 % |
| HrS3 | Pre-CC | chr15:72.2–76.0 | Eosinophilia (4dpi) | A/BCDEFGH | 26 % |
| HrS4 | Pre-CC | chr13:52.7–54.9 | Perivascular cuffing (4dpi) | F/ABCDEGH | 21 % |
| CC-RIX (herein) | |||||
|---|---|---|---|---|---|
| HrS10 | CC-RIX | chr13: 20.3- 23.7 | HKU3-MA mortality | FG/ABCDEH | OR* 6.13 |
| HrS11 | CC-RIX | chr5: 112.9–118.8 | HKU3-MA mortality | C/ABDEFGH | OR* 10.45 |
| HrS12 | CC-RIX | chr15: 51.5- 75.6 | HKU3-MA weight loss (4dpi) | G/ABCDEFH | 3.4 % |
| HrS13 | CC-RIX | chr16:18–51.1 | SARS viral titer (2dpi) | C/G/ABDEFH | 15.94 % |
| HrS14 | CC-RIX | chr11: 9.05- 28.66 | PenH (2dpi) | D/CEH/ABFG | 11.65 % |
| HrS15 | CC-RIX | chr11: 3.26- 28 | Rpef (4dpi) | ABCEFGH/D | 6.48 % |
| HrS17 | CC-RIX | chr17: 27.4- 78.3 chr17: 27.4- 78.3 |
IgG1 (N) (32dpi) Total IgG (N) (32dpi) |
A/BCDEFH/G | 19.97 % 18.53 % |
| HrS18 | CC-RIX | chr16: 18.1- 43.8 | Total IgG (N) (32dpi) | ABCDEFH/G | 22.75 % |
| HrS19 | CC-RIX | chr10: 17.4- 130.5 | Total IgG (N) (32dpi) | ABCDEH/FG | 10.71 % |
| HrS20 | CC-RIX | chr3: 3.1- 35.4 | Total IgG (N) (32dpi) | G/ABCDEFH | 10.83 % |
| HrS22 | CC-RIX | chr6:67.2- 85 | CD8+ DCs [%] (4dpi) | F/ABCDEGH | 8.17 % |
| CC011xCC074-F2 (Schafer et al., 2022) | |||||
|---|---|---|---|---|---|
| HrS24 | CC011xCC074-F2 | chr4:32.95–114.54 | Mortality | CC011: G,H,C CC074:A/H, A/D, D, E, F |
OR* 4.34 |
| HrS25 | CC011xCC074-F2 | chr4: 6.38–17.97 | Weight loss in males (4dpi) | CC011: G, B CC074: A |
12.57 % |
| HrS26 | CC011xCC074-F2 | chr9:74.94–124.06 chr9:117.38–124.07 chr9:116.24–124.07 chr9:111.54–122.63 chr9:111.54–122.63 |
Mortality Hemorrhage (4dpi) PenH (2dpi) Periph. neutrophils (4dpi) Periph. lymphocytes (4dpi) |
CC011: B, G CC074: A |
OR* 3.15 10.24 % 7.76 % 11.8 % 12.39 % |
| HrS27 | CC011xCC074-F2 | chr11:26.44–80.76 chr11:17.89–80.76 |
Periph. neutrophils (4dpi) periph. lymphocytes (4dpi) |
CC011: H, B, H CC074: C |
5.5 % 5.6 % |
| HrS28 | CC011xCC074-F2 | chr15:58.66–74.04 | PenH (2dpi) | CC011: H CC074: B |
8.48 % |
| CC003xCC053-F2 (Gralinski et al., 2017) | |||||
|---|---|---|---|---|---|
| HrS5 | CC003xCC053-F2 | chr18:24.76–51.25 chr18:31.63–51.25 chr18:42.85–73.43 chr18:31.63–65.17 chr18:42.85–65.17 chr18:24.76–51.2 chr18:24.76–51.2 |
Weight loss (3dpi) Weight loss (4dpi) Congestion score (4dpi) Perivascular cuffing (4dpi) Edema (4dpi) Viral titer (4dpi) |
CC003: A, G CC053: C/G, G, B, B/D, B/C, D |
6 %−13.2 % |
| HrS6 | CC003xCC053-F2 | chr9:121.77-end | Weight loss (3dpi) | CC003: B, B/D CC053: H |
7 % |
| HrS7 | CC003xCC053-F2 | chr7:83.45–129.93 chr7:69.79–96.66 |
Weight loss (4dpi) Viral titer (4dpi) |
CC003: B, C, B/C CC053: G/H, H, D |
6.8 % 14.4 % |
| HrS8 | CC003xCC053-F2 | chr12:88.54–103.21 | Viral titer (4dpi) | CC003: D CC053:F/H |
4.27 % |
| HrS9 | CC003xCC053-F2 | chr15:10.7–57.3 | Congestion score (4dpi) | CC003: G, E/G, G CC053: D, C, F |
9.4 % |
| HrS23 | CC003xCC053-F2 | chr4:35.61–104.04 chr4:35.61–104.04 |
Congestion score (4dpi) Weigh loss (4dpi) |
CC003: H, E, G, H CC053: F, G, F |
6.86 % 6.22 % |
QTL influencing mortality calculate an Odds Ratio (OR) for disease rather than a% of variation explained. For both the CC-RIX and the CC-F2, Odds Ratios for specific loci are calculated with a full model of all mortality loci, to better estimate their independent effects.
Haplotype effects are described for each QTL. For the Pre-CC and CC-RIX, the haplotypes are separated based on the allele effect splits between founder haplotypes (A = A/J, B = C57BL/6 J, C = 129S1/SvImJ, D=NOD/ShILtJ, E=NZO/HiLtJ, F=CAST/EiJ, G=PWK/PhJ, H=WSB/EiJ). In CC-F2 crosses, the haplotypes listed are those present in the given parent strains from the proximal to distal ends of each region’
HrS10, HrS11, and HrS12: QTLs for HKU3-MA infection; all other QTLs are for SARS-CoV.