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n n n u n n n n u n n n n n n n u y n y n n y n n n n n u n n n n n n y n n n n 21 L x n y n y u u y x y n y x n y n x n u u x u n n x u n y

u u y y u n n n u u n n n u u n y n u n n y n n n n y n n n n y x n y n n n u n n y n n x n y n n n n n n n n n u n n n x n u n y x n y n n n y n u n n n y n 22 I n n x n y n n u n n n n n n n u u n n n u n u n n n n x n y n n y n y n n y n n nu n y n n n n u n n n n n u n u In n u n y n n un n n y n n n n n n n u n n y n n un n n x n L u n y n n x n un n n n n y n u x n u n x n y n n n y u n u n y In u y x y n u n u u y n n y u n n n u y n y n u n y n u n n y n n u u n y y n u x n n n n n n u x n n n n nu y n y In u n n y u u y n u n u n u n n n n y n y n u nn u n u n u n u y x u x n n n n nu y n y n u n n n n n y nu y In n u u n u n n n x y In n u y L x n y n y u u y x n y n n n n n n n n n n n y n y n n n u n n n u n n n nu x u n u n u y n u n u u u n n n n n n y n n n u In n y n y n n n n nu u n u y n x u n y u n n y u n y n n n n u x u n y n y u x n u n Table 1: Composition of our data set of 1733 boxer dogs in relation to the original post-weaning cohort of boxer dogs (n= 1863).

number of boxer % dogs in follow up, alive 674 In follow up, dead 506 lost to follow up after 553 weaning Number of dog in data set 1733 excluded from analysis total post weaning cohort For a binary trait it is difficult to analyse differences in risk factors within small litters.

Therefore, litters with less than three puppies were excluded from the statistical analysis.

n u n n y n n n n n n n y n n In u n n n n y y n n n u n u n y u n nu u n u n nu n n u n y u y n u n y n u y n u n n u n u n u y n u n n n y u n n n y u u n Table 2: Levels used in the risk factors: age of the dam (n=3), parity of the dam (n=3), season (n=7), litter-size (n=5), and preweaning-mortality (n=2) included in the full model fitted to the survival with age in a birth cohort of boxer dogs.

level age of dam parity of season litter preweaning (yrs) dam (mo yr) size mortality (%) 1 1-3 1 jan + feb 94 3-8 0 - pups 2 3-4 2 mrt + apr 94 9 41 - pups 3 4-7 > 2 may + jun 4 july + aug 5. sept + okt 6 nov + dec 7 jan + feb litters of less than three pups were excluded from the analysis n x n y n x u n n n u u n n n u n n n u y n n n u u u un n n n n u y u n ny (t;

w)=0 (t)exp{w'} n un n n n n u n x n n In u n y n un n x y u un n n u y u n n u n y u In x n I n y y n u n n n u n n u n u u n I n n u u n n u n u n y u u u I n un u I y x n n n y u n x n n u n u y x n y u u n y n u n x n n n u u n n y n y x x n u n x n n u n n u L x n y n y u u y x n x n n u y n n n n nu u n n n y n n n n n u n n n un n y n n n n u u u n n u n u n n n n u n n n y n n n n u u n n n n n u n n n n L n u n n n nL nL u u n u n n n n nu un n n n n n Table 3: Chi-square (2) values and associated degrees of freedom (df) for the risk factors, included in the full model, fitted to age at mortality with random litter effects in the post-weaning cohort of Dutch boxer dogs (n=1733).

full model d 2 prob > f litter:

age of dam 2 1.33 0. parity of dam 2 0.98 0. inbreeding coefficient 1 5.43 0. season of birth 6 11.48 0. litter size 1 5.15 0. preweaning 1 1.88 0. mortality % individual :

gender 1 3.24 0. castration 1 23.34 0. n u un n y u un n n n u n y n y n x n n n n n n n n n n n u n n n u n u n n n n n u n u n u n u n n u u n n u y x n n n u n u n nu n n x n n n y u n n y n u n u n n u n u n n n n u n u n n n n y n n u n y n n y n u y n n y n n un n n n ny u un n n y n n n u nn u n n x y u nn u n u n u n n n x n n n u x u n n x u n n n n L x n y n y u u y x nn n u y n n n x u u y n u u Figure 1: The life expectancy of boxer dogs that survived up to day (t) of the observation period, from 49 days up to 10 years of age, in years in a Dutch post-weaning cohort of boxer dogs.

0, 0, 0, 0, 0, 0, 0, Survival of the post-weaning cohort 0, 0 2 4 6 8 age in years n nu n n u n n u n n u n y y n n y x In y y y u n u n y y y u n y n y n u y un y u y y u y Figure 2. The frequency of age at mortality in the 10-year follow-up study of a Dutch post-weaning cohort of boxer dogs (n=506).

Frequency 0 1 2 3 4 5 6 7 8 age at mortality in years survival n n n n n n u u u n u n n n n n Table 4: Estimates ( elog hazard) of the final parametric survival model of the 506 deaths at different age (dependent variable), with random litter effects (n=1733). The risk ratio (hazard ratio) is derived from e estimate.

level estimate se X2 prob > X2 relative 95%CI rate inbreeding continuous -0.22 0.096 5.09 0.02 * * litter size 3-8 0.00 * * * 1.00 * -0.28 0.14 4.31 0.04 0.75 0.57 - 0. season of jan + feb 94 -0.13 0.15 0.84 0.36 0.87 0.65 1. birth mrt + apr 94 0.00 0.15 0.00 1.00 1.00 0.75 - 1. may + jun 94 0.00 * * * 1.00 * july + aug 94 -0.27 0.17 2.70 0.10 0.76 0.55 1. sept + okt 94 -0.17 0.17 1.00 0.32 0.85 0.61 1. nov + dec 94 -0.29 0.16 3.06 0.08 0.75 0.55 1. jan + feb 95 -0.49 0.19 6.63 0.01 0.61 0.42 0. preweaning 0-40% 0.000 * * * 1.00 * mortality >40% 0.23 0.16 1.91 0.17 1.26 0.92 1. gender M 0.000 * * * 1.00 * F -0.16 0.09 3.00 0.08 0.86 0.71 1. castration no 0.00 * * * 1.00 * yes 0.54 0.11 24.87 0.00 1.71 1.38 2. Ninety-five percent confidence interval, The inbreeding coefficient in %.

n u n n u n u n n n n u y n un n n y n n n n n nu u n n y n n nu y n u y y n n y y y n n y n n u n y n n u y n n y n u n y n n n un y u n y y n n n u n n u n H n y y un n x n n n n u n n u n u n n n n x n y u n u n n x n y ny n n u x n y ny L x n y n y u u y x u n n x y u u ny u n Figure 3. The predicted life expectancy of boxer dogs that survived up to day (t), of the progeny of the 10 best sires (with the lowest average estimated breeding value (EBV): good_EBV), and the of the 10 worst sires (with the highest average EBV: bad_EBV) compared to proportion of CCL free dogs in our study (km-est).

0, 0, 0, 0, 0, post-weaning cohort 0, progeny of the best 10 sires:good_ebv progeny of the worst 10 sires:bad_ebv 0, 0, 0 2 4 6 8 ---> age in years u x n n n u n u n y un u u n n n n y y x n n x n n n u n n n u y n n y n u x In u u y un y u u n y n u y y u n u y n n y n u n y n n n y u In n u y y u n x n u n x un n y y n n y x n n u u y x n n u un --->(predicted)survival u n y n n u y n In n n n n u n n y nn n y y n n n y n n n n u n n n n n n n n u y u u n n y n u u y n n y n n n n x u n u u n n y y n u n u n n n y y n n n n u n n n n n n y L n n n n n n n n un n n n y n u u y y y u x u n u n y n n y n n n n u n n n n n n n y In n u un n n y n n x n In u y n n y n n u n n n u n n n n u y nn x u n n u u y n u u n n n u u n n y n n y n y n u n n u n n u y n u n I u n y u n n n x n u n n n n n n n n n n n u y y n In u y n y n y y n n y xu y n u xu y n nu u n u y u n n u n u u y u n u n n u n n u n y u u n n u n n n u n u u n n x y n u n n n n un n y n n n n u n n y n n n n n u n n n n u n n x n n n n n n n u n n n n u u n y n u n n n n n u n n n n n n u u n n x L x n y n y u u y x y n u n n n n n u u n y y n n u x u n n y n n y n n n n n n y n y n n n n n n un n u u y n n n y n u n y n n x n y u u u y n u y n n n n un n u n n n u n u y u n n u n n u u n y u u u n u y u nn u n x u n n n n n n n n n n n n n n n nu n u u n L n y n n x u n n n y n y n y n n n n n n y n n u n u In n n n n u u u n n y n u nn n n y n n u n u n u n nn n n n u n y n y n n u n n u n n n nn u n I n y n n u n n u n n u n u n n y n n L x n y n u n I u n n x n u n L n n n u n n n u u u n n L n I n u n In n y n n n n x u n n L u n u n n n n n n n n y n u u n n u n y u n n n n L u n u nu u n n y n n y u n u n y n L n n n n n u y n n y x u u n y y n u n n n n n n n L n LL n y n u y n n x y u y u n x n n n y L n n u L n n L u n u n n n n n n n n y n u L x n y n y u u y x n n n n n u n x n n n y L n Lun n n n u y n y n L n n n n u n n y u y u n n u L n y n L n n u n y u n n u n y n n n y n In n n n n n n I n un n I L n y uy n n




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