Table 1.
Paternal transmissions
| Model | Parental genotype compared to +/+ | Msh 2 | Xpc | Msh 6 | Msh 3 | ||||
|---|---|---|---|---|---|---|---|---|---|
| OR (99% CI) |
p-value | OR (99% CI) |
p-value | OR (99% CI) |
p-value | OR (99% CI) |
p-value | ||
| Multinomial (cumulative higher changes vs. cumulative lower changes) | -/- | 0.20 (0.04, 0.92) |
0.0065 | 1.03 (0.52, 2.02) |
0.91 | 1.18 (0.46, 3.03) |
0.65 | 0.44 (0.15, 1.35) |
0.061 |
| +/- | 0.41 (0.04, 4.54) |
0.34 | ND | ND | 0.43 (0.07, 2.72) |
0.24 | 0.51 (0.14, 1.84) |
0.17 | |
| changed vs. unchanged | -/- | 0.52 (0.18, 1.48) |
0.11 | 0.55 (0.26, 1.20) |
0.05 | 1.43 (0.67, 3.03) |
0.23 | 0.88 (0.32, 2.42) |
0.74 |
| +/- | 0.54 (0.85, 3.45) |
0.39 | ND | ND | 4.98 (2.72, 9.14) |
< 0.0001 | 0.35 (0.12, 1.04) |
0.013 | |
| ‘Risk’ expansions vs contractions+unchanged | -/- | NR | NR | 0.88 (0.36, 2.16) |
0.72 | 1.40 (0.63, 3.13) |
0.28 | 0.59 (0.27, 1.31) |
0.089 |
| +/- | NR | NR | ND | ND | 1.16 (0.24, 5.52) |
0.81 | 0.40 (0.13, 1.22) |
0.034 | |
| ‘protective’ contractions vs expansions+unchanged | -/- | 2.13 (0.36, 12.64) |
0.28 | 0.09 (0.003, 2.59) |
0.07 | 1.15 (0.26, 5.11) |
0.81 | 1.79 (0.31, 10.35) |
0.39 |
| +/- | 1.40 (0.06, 30.71) |
0.78 | ND | ND | 4.28 (1.02, 18.00) |
0.009 | 0.67 (0.09, 4.98) |
0.61 | |
Results of running four statistical models to determine the effect of Msh2, Xpc, Msh6 and Msh3 DNA repair genes on the intergenerational instability of the HdhQ111 CAG repeat in paternal transmissions. Odds ratios (OR) with 99% confidence intervals (CI) and p-values are given for each model for comparisons between fathers that were deficient in either one (+/-) or two (-/-) copies of each of the DNA repair genes and the respective wild-type (+/+) controls. Values in bold are statistically significant. Values in italics indicate trends that did not reach significance. A p-value of 0.01 was used to determine significance (see Materials and Methods). NR: the ‘Risk’ model was not run as there were zero data points in the expansion group. ND: Xpc heterozygotes were not analyzed. Msh2: 116 total transmissions from 9 fathers; Xpc: 139 total transmissions from 12 males; Msh6: 144 total transmissions from 11 males; Msh3: 134 total transmissions from 12 males.