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Genetic analysis of primary cataract, persistent pupillary membrane and distichiasis parameters was confined on the traits CAT, CAT-juvenil, CAT-late, PPM and DIST. Pedigree information over eight generations was considered. The completeness of pedigrees was larger than 91% in all eight generations for both single- and multi-colored ECS. Because the average coefficient of coancestry in all animals born after 1999 was 2.1% within the single-colored and 1.8% within the multi-colored ECS, but only 0.09% between single- and multi-colored ECS, all analyses were performed separately for single-colored and multi-colored ECS. All traits were included as dependent dichotomously distributed variates in the multivariate animal model: Yijkl = µ + Fi + b*cj + ak + eijkl where Yijkl is the occurrence of the respective eye disease (0/1 trait) of the k-th animal, µ is the model constant, Fi represents the trait-specific systematic effects, cj represents the traitspecific covariate with linear regression coefficient b, ak is the random additive genetic effect of the animal, and eijkl is the random residual effect. The number of animals included in the additive relationship matrix was 3931 for the singlecolored and 3936 for the multi-colored ECS, including 615 single-colored and 617 multicolored animals with ophthalmological records and 895 single-colored and 857 multi-colored ECS base animals (founders) without records. Models for the genetic analyses were developed on the basis of the results of single and multiple analyses of variance using the GENMOD and GLIMMIX procedures of SAS (Statistical Analysis System), version 9.1.3 (SAS Institute, Cary, NC, USA, 2006). We used a binomial distribution function and the probit function as link function for the generalized linear model. Significance level was set to P < 0.05. Analyses of variance were performed separately for single-colored and multi-colored ECS. The following factors were tested as fixed effects: sex (female, male), year of birth (≤1996, 1997 to 1998, 1999 to 2000, 2001 to 2002, >2002), month of birth (January to March, April to June, July to September, October to December), litter size (≤3, 4 to 5, 6 to 7, >7), inbreeding coefficient (≤0.01, >0.01 to 0.04, >0.04), number of ophthalmological examinations in ECS as indicator for the experience of the veterinary ophthalmologists (≤5, 6 to 20, >20), percentage of examined animals per kennel (≤5.0, >5.0 to 10.0, >10.0), percentage of examined animals per litter (≤15.0, >15.0 to 20.0, 20.0 to 30.0, 30.0 to 50.0, >50.0), number of ophthalmological examinations per animal (singularly ophthalmologically examined, multiply ophthalmologically examined), age at first 34
Genetic analysis of primary cataract, persistent pupillary membrane and distichiasis diagnosis for dogs affected by CAT or at last ophthalmological examination for dogs unaffected by CAT (0 to 1.5, 1.5 to 3.5, 3.5 to 5.5, >5.5 years) and age at first diagnosis for dogs affected by PPM or age at first ophthalmological examination for dogs unaffected by PPM (≤1.5, 1.5 to 3.5, >3.5 years). Inbreeding coefficient was considered as linear covariate. The effects of dam, litter, kennel and veterinary ophthalmologist were treated as random effects. The percentage of variance explained by dam, litter, kennel or veterinary ophthalmologist was less than 0.22% in the single-colored and less than 0.11% in the multi- colored ECS. None of the considered random effects had a significant influence on the prevalence of the PIED analyzed in this study. The final model for single-colored and multi-colored ECS included age at first diagnosis or at last ophthalmological examination as fixed effect for CAT, inbreeding coefficient as linear covariate for CAT, CAT-early and CAT-late, age at first diagnosis or at first ophthalmological examination as fixed effect for PPM and number of ophthalmological examinations per dog as fixed effect for DIST. Heritabilities (h 2 obs) and additive genetic (rg) and residual correlations (re) were calculated from the estimated additive genetic (σa 2 ) and residual variances (σe 2 ) and covariances (cova, cove): h 2 obs = σa 2 / σp 2 = σa 2 / (σa 2 + σe 2 ) rg = cov(a1,a2 ) / σa1σa2 re = cov(e1,e2 ) / σe1σe2 In order to compensate for the underestimation of heritabilities of binary traits in linear model analyses, the estimated heritabilities and residual correlations were transformed from the linear model into the threshold model according to Dempster and Lerner (1950) and Vinson et al. (1976): h 2 DL = h 2 obs [pi (1- pi )] / zi 2 with h²DL = heritability of trait i on the underlying continuous scale, h²obs = heritability of trait i on the observed scale, pi = frequency of outcome 1 for trait i, and zi = ordinate of a standard normal distribution at the threshold point corresponding to a fraction pi of the population which has the character in question. reV = reobs {[pi (1- pi )] / zi 2 } 1/2 {[pj (1- pj )] / zj 2 } 1/2 35
Page 4 and 5: Bibliografische Informationen der D
Page 6 and 7: Wissenschaftliche Betreuung: Prof.
Page 9 and 10: Contents Chapter 1 Introduction …
Page 11 and 12: Introduction CHAPTER 1 Introduction
Page 13 and 14: Introduction Hannover. Chapter 2 re
Page 15 and 16: Review of canine primary cataract C
Page 17 and 18: Review of canine primary cataract 1
Page 19 and 20: Review of canine primary cataract p
Page 21 and 22: Review of canine primary cataract (
Page 23 and 24: Review of canine primary cataract R
Page 25 and 26: Review of canine primary cataract E
Page 27 and 28: Review of canine primary cataract K
Page 29 and 30: Review of canine primary cataract S
Page 31 and 32: Review of canine primary cataract T
Page 33 and 34: Table 3 (continued) Review of canin
Page 35 and 36: Table 3 (continued) Review of canin
Page 37 and 38: Genetic analysis of primary catarac
Page 43: Genetic analysis of primary catarac
Page 63 and 64: Retrospective study on prevalence a
Page 81 and 82: CHAPTER 5 Genetic evaluation of pri
Page 83 and 84: Zusammenfassung Auf der Basis von o
Page 85 and 86: Materials and methods The results o
Page 87 and 88: Results The 615 ophthalmologically
Page 89 and 90: Discussion Phenotype based selectio
Page 91 and 92: References BARNETT, K.C. (1976): Co
Page 93 and 94: Tab. 2: Means and ranges of relativ
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Tab. 4: Prevalences of early onset
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Fig. 1: Cumulative percentages of p
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Fig. 3: Cumulative percentages of p
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Evaluation of canine HSF4 with here
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Molecular genetic analysis of prima
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Position of gene (Mb) Molecular gen
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General discussion General discussi
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General discussion (Rubin, 1989; Ge
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General discussion References Barne
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General discussion 132
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Summary Anja Engelhardt (2007) Summ
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Summary advantageous selection stra
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Erweiterte Zusammenfassung Anja Eng
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Zusammenfassung und 617 mehrfarbige
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Zusammenfassung einem einfachen rez
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Zusammenfassung Evaluierung des Hit
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Zusammenfassung Kopplungs- und Asso
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Appendix Appendix Table 1 Survey of
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Appendix Table 3 Survey of 45 micro
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Table 3 (continued) Appendix VI
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Position of gene (Mb) Table 4 (cont
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Position of gene (Mb) Appendix Tabl
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Position of gene (Mb) Table 5 (cont
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Appendix Legend for pedigrees consi
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Appendix Figure 2 Second pedigree o
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Appendix Figure 4 Pedigree of wire-
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Appendix Figure 6 Pedigree of subfa
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Laboratory paraphernalia Equipment
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dNTP solution Appendix 100 µl dATP
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Enzymes Appendix Taq-DNA-Polymerase
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Publications CHAPTER 12 List of pub
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Publications XXX
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Acknowledgements Acknowledgements M
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