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Genomische, Molekulargenetische Und Phänotypische Analysen Zu Robustheit Und Resistenz Am Beispiel Endoparasitärer Infektionen Bei Milchkühen

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Genomische, Molekulargenetische Und Phänotypische Analysen Zu Robustheit Und Resistenz Am Beispiel Endoparasitärer Infektionen Bei Milchkühen Aus dem Institut für Tierzucht und Haustiergenetik Professur für Tierzüchtung der Justus-Liebig-Universität Gießen Genomische, molekulargenetische und phänotypische Analysen zu Robustheit und Resistenz am Beispiel endoparasitärer Infektionen bei Milchkühen INAUGURAL – DISSERTATION zur Erlangung des Doktorgrades (Dr. agr.) im Fachbereich Agrarwissenschaften, Ökotrophologie und Umweltmanagement der Justus-Liebig-Universität Gießen vorgelegt von Katharina May aus Kassel Gießen, November 2019 Mit Genehmigung des Fachbereiches Agrarwissenschaften, Ökotrophologie und Umweltmanagement der Justus-Liebig-Universität Gießen Dekan: Prof. Dr. Klaus Eder Prüfungskommission: 1. Gutachter: Prof. Dr. Sven König 2. Gutachter: Prof. Dr. Jens Tetens 3. Gutachter: Prof. Dr. Matthias Gauly Prüfer: Prof. Dr. Klaus Eder Prüfer: Prof. Dr. Horst Brandt Tag der Disputation: 13. Februar 2020 Diese Arbeit wurde durch ein Promotionsstipendium der H. Wilhelm Schaumann Stiftung gefördert. Teile dieser Arbeit wurden durch das Bundesministerium für Ernährung und Landwirtschaft (BMEL) gefördert (Förderkennzeichen: 12NA035, 281BM090). INHALTSVERZEICHNIS ZUSAMMENFASSUNG ......................................................................................................... 1 SUMMARY ............................................................................................................................... 8 KAPITEL 1 ............................................................................................................................. 13 Einleitung 1.1 Zucht auf Robustheit beim Milchrind .......................................................................... 13 1.2 Resistenz, Toleranz und Widerstandsfähigkeit ............................................................ 16 1.3 Endoparasiteninfektionen und deren wirtschaftliche Bedeutung in Milchproduktionssystemen........................................................................................... 17 1.3.1 Infektionen mit gastrointestinalen Nematoden ........................................................ 17 1.3.2 Infektionen mit dem Rinderlungenwurm ................................................................. 18 1.3.3 Infektionen mit dem großen Leberegel .................................................................... 19 1.4 In der Zucht verwendete Merkmale einer Endoparasitenresistenz ............................... 20 1.5 Genetik der Endoparasitenresistenz beim Rind ............................................................ 22 1.6 Genomische Ansätze zur Zucht auf Endoparasitenresistenz beim Deutschen Schwarzbunten Niederungsrind.................................................................................... 24 Ziele der Arbeit ........................................................................................................................ 25 Referenzen. ............................................................................................................................... 27 KAPITEL 2 ............................................................................................................................. 35 Phenotyping strategies and quantitative-genetic background of resistance, tolerance and resilience associated traits in dairy cattle............................................................... 35 KAPITEL 3 ............................................................................................................................. 66 Genome-wide associations and functional gene analyses for endoparasite resistance in an endangered population of native German Black Pied cattle .................................... 66 KAPITEL 4 ........................................................................................................................... 116 Allele substitution and dominance effects of CD166/ALCAM gene polymorphisms for endoparasite resistance and test-day traits in a small cattle population using logistic regression analyses ..................................................................................................... 116 KAPITEL 5 ........................................................................................................................... 156 Fasciola hepatica seroprevalence in Northern German dairy herds and associations between bulk tank milk antibody levels with milk production parameters and milk ketone bodies ß-hydroxybutyrate and acetone ........................................................... 156 KAPITEL 6 ........................................................................................................................... 183 Diskussion 6.1 Genetisch-statistische Modellierungen zur Endoparasitenresistenz ........................... 183 6.2 Phänotypisierung und Merkmalsverteilung ................................................................ 184 6.3 Genomweite Assoziationsstudien für Endoparasitenmerkmale ................................. 186 6.4 Beziehungen und Korrelationen zwischen Endoparasitenmerkmalen ....................... 189 6.5 Beziehungen und Korrelationen zwischen Endoparasitenmerkmalen mit der Milchleistung und der Eutergesundheit ...................................................................... 190 6.6 Kandidatengene und Pathways für Endoparasitenmerkmale ..................................... 191 6.7 Allelsubstitutionseffekte für Endoparasitenmerkmale, Milchproduktionsmerkmale und weitere Resistenzmerkmale im ALCAM Gen ............................................................. 192 6.8 Dominanzeffekte für Endoparasitenmerkmale, Milchproduktionsmerkmale und weitere Resistenzmerkmale im ALCAM Gen ............................................................. 194 6.9 Züchterische Möglichkeiten basierend auf imputeten Daten und Vollgenomsequenzdaten............................................................................................. 196 6.10 Fasciola hepatica Seroprävalenzen und phänotypische Assoziationsanalysen mit Milchproduktionsmerkmalen ..................................................................................... 197 6.11 Phänotypische Assoziationsanalysen zwischen F. hepatica-Infektionen und Milchketonkörpern ..................................................................................................... 199 6.12 Praktische Aspekte der Zucht auf Endoparasitenresistenz und Forschungen zur Wirt- Parasiten-Interaktion................................................................................................... 201 Schlussfolgerungen der Arbeit ............................................................................................... 203 Referenzen. ............................................................................................................................. 205 ERKLÄRUNG ...................................................................................................................... 215 TABELLENVERZEICHNIS KAPITEL 1 Tabelle 1. In der Literatur angegebene Heritabilitäten (nach Publikationsjahr) für verschiedene Merkmale zur Erfassung von Infektionen mit gastrointestinalen Nematoden (GIN), D. viviparus und F. hepatica………………………………………………………………………………. 21 KAPITEL 2 Table 1. Heritability estimates in HF dairy cows for novel biomarkers (somatic cell count and fat-to-protein ratio not included) as indicators of resistance, tolerance and resilience associated traits in studies as from 2000 (ordered chronologically for each biomarker) …………………48 Table 2. Literature overview for genetic correlations between objectively measurable immune response traits and production traits in dairy cattle……………………………………………55 KAPITEL 3 Table 1. Descriptive statistics for endoparasite traits for all cows and for genotyped DSN cows…………………………………………………………………………………………. 72 Table 2. Chromosome-wide significance thresholds for the endoparasite traits rFEC-GIN, rFEC-FH and rFLC-DV including the number of SNP markers after quality control (QC) and the effective number of independent SNP markers based on linkage disequilibrium (LD) calculated using the software GEC (Lie et al., 2012) ………………………………………….76 Table 3. List of all SNP markers associated with the residuals of gastrointestinal nematodes (rFEC-GIN) identified in Black Pied dairy cattle by genome-wide analysis………………….86 Table 4. List of all SNP markers associated with the residuals of Fasciola hepatica (rFEC-FH) identified in Black and White dairy cattle by genome-wide analysis………………………….86 Table 5. List of all SNP markers associated with the residuals of Dictyocaulus viviparus (rFLC- DV) identified in Black and White dairy cattle by genome-wide analysis………………………………………………………………………………………. 87 Table 6. Potential candidate genes related to the identified regions associated with endoparasite resistance traits………………………………………………………………………………. 93 Table 7. Candidate genes related to pathways potentially associated with endoparasite resistance……………………………………………………………………………………. 95 KAPITEL 4 Table 1. Descriptive statistics of endoparasite traits and test-day production traits from dataset 1……………………………………………………………………………………………. 121 Table 1. Details of sequencing primers used for the bovine activated leukocyte cell adhesion molecule gene (ALCAM)…………………………………………………………………….124 Table 3. Identified SNPs in the bovine ALCAM gene on BTA 1 from dataset 2 in German Back Pied cattle (DSN)…………………………………………………………………………….130 Table 4. Genotype frequency of the chip SNP ALCAMc.73+32791A>G, of the SNP ALCAMc.1017T>C in exon 9 and of the SNPs ALCAMc.1104+10T>A and ALCAMc.1104+85T>C in intron 9 of the ALCAM gene for all 94 cows from dataset 3……132
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