Genomic architecture and complex traits in norwegian red cattle

The predominant cattle breed in Norway, Norwegian Red cattle (NRF), is an admixed breed formed from local Norwegian breeds and imported animals from other Nordic breeds. The extensive phenotypic records for NRF represent a unique resource for studying genetic factors affecting complex traits of importance for animal production. Phenotypic records of traits related to milk production, meat production and fertility, as well as health traits such as veterinary treated clinical mastitis, are now kept for 96% of Norwegian cattle. Records of veterinary treated clinical mastitis have been kept for most NRF animals for the last three decades. Mastitis is inflammation of the mammary gland and is the most widespread disease affecting dairy cattle world-wide. Consequences of this disease include animal suffering, reduced milk quality, unwanted use of antibiotics and a more costly production. Main objective of the work described in this doctoral thesis has been to study the genomic architecture of the admixed NRF breed in order to understand the genetics underlying complex traits in cattle, particularly susceptibility to mastitis. The study was initiated with the genotyping of 2,589 NRF bulls for single-nucleotide polymorphisms (SNPs) using the Bovine Affymetrix 25k MIP SNP array. Construction of linkage maps provided a powerful resource for quality assessment of the bovine genome assembly Btau_4.0 and for investigations of recombination rates and linkage disequilibrium (LD) across the NRF genome. Differences between recent and historic recombination rates were used to identify genomic loci subjected to strong artificial selection in the observed pedigree. Reduced LD was found in NRF compared with other breeds included in the study. The high LD generally reported in cattle facilitates association mapping studies for detection of quantitative trait loci (QTLs) affecting complex traits. In order to detect QTLs affecting susceptibility to mastitis genome-wide association studies with over 17,000 SNPs were performed for occurrence of clinical mastitis (CM) in seven lactational time periods and for lactation average somatic cell score (SCS). Although there is a genetic correlation between CM and SCS, no consistencies were found between SNPs significantly associated with CM and those associated with lactation average SCS. Combined linkage and linkage disequilibrium analysis confirmed quantitative trait loci for CM on bovine chromosomes 2, 6, 14 and 20, with the highest test score for CM being found for a SNP at 90.67Mb on chromosome 6. In addition to the QTL for CM on chromosome 6, a QTL affecting milk protein yield (PY) has been found to coincide with the casein genes around 88Mb on this chromosome. Fine mapping gave highest test scores for PY in and around the casein genes CSN2 and CSN1S2 (at 88.33Mb and 88.41Mb), while highest test scores for CM were found within the region 89 to 91Mb. It has been suggested that a haplotype encompassing the casein genes, with a favorable effect on PY and an unfavorable effect on CM, was introduced into the NRF population through importation of a Holstein-Fresian bull (1606 Frasse) in the 1970s. High-throughput re-sequencing allowed for molecular characterization of the long range haplotype from 1606 Frasse and revealed plausible causal polymorphisms in the promoter region of the gene CSN1S2 and in a known regulatory motif in the 5’-flanking UTR of CSN1S2.Norsk Rødt fe (NRF) er en syntetisk rase basert på norske raser og importerte dyr fra andre nordiske raser. Fenotypiske egenskaper relatert til melkeproduksjon, kjøttproduksjon og fruktbarhet, i tillegg til helseegenskaper som veterinær behandlet klinisk mastitt, registreres nå for 96 prosent av norsk storfe. Dette materialet utgjør en unik ressurs for studier av komplekse egenskaper av økonomisk viktighet. Tilfeller av veterinær behandlet klinisk mastitt er blitt registrert for de fleste NRF dyr i over 30 år. Mastitt er en betegnelse på inflammasjon i melkekjertelen og er den vanligste sykdommen i melkekyr på verdensbasis. Resistens mot mastitt i storfe forventes å være påvirket av både genetiske og miljømessige faktorer, og refereres til som en kompleks egenskap. Hovedmålsetningen med dette doktorgradsarbeidet har vært å studere genomets oppbygning og variasjon i NRF og å bruke denne informasjonen til å forstå mer av genetikken bak økonomisk viktige egenskaper i storfe, og da spesielt mastittresistens. Studien ble innledet med genotyping av 2,589 NRF okser for enkelt-nukleotid polymorfismer (SNPer) fra den bovine Affymetrix 25k MIP SNP arrayen. Koblingskart konstruert i dette materialet ble brukt til kvalitets kontroll av det bovine genomassembliet (Btau_4.0) og for å studere rekombinasjonsrater og grad av koblingsulikevekt i NRF. Forskjeller i nylig og historisk rekombinasjonsrate ble brukt til å identifisere regioner i genomet som kan ha vært utsatt for sterk seleksjon. Redusert koblingsulikevekt ble funnet i NRF sammenlignet med andre storferaser inkludert i studien. Den generelt høye koblingsulikevekten i storfe er nyttig for deteksjon av områder i genomet som påvirker komplekse egenskaper (QTLer). For å detektere QTLer for mastittresistens ble det gjennomført en helgenom assosiasjonsstudie med over 17,000 SNPer. Registreringer på mastitt ble delt inn i syv tidsperioder i laktasjonen. I tillegg var celletall i melk inkludert som et indirekte mål på sykdommen. Selv om det er genetisk korrelasjon mellom klinisk mastitt og celletall i melk avdekket ikke dette studiet SNPer som var signifikant assosiert med begge egenskapene. QTLer for klinisk mastitt ble identifisert på kromosom 2, 6, 14 og 20, og høyeste testverdi ble funnet for en SNP ved 90.67Mb på kromosom 6. I tillegg til QTLen for klinisk mastitt rundt 90Mb på kromosom 6 ble det også funnet en QTL for protein mengde i melk ved kasein genene omkring 88Mb. En finkartlegging i området pekte ut kasein genene CSN2 og CSN1S2 (ved 88.33Mb og 88.41Mb) som mest sannsynlig QTL område for proteinmengde, mens sterkest assosiasjon med klinisk mastitt ble funnet for SNPer i regionen 89 til 91Mb. Tidligere studier har foreslått at en haplotype som dekker kasein genene, med en positiv effekt på protein mengde i melk og en negativ effekt på mastitt resistens, ble introdusert i NRF populasjonen ved import av en Holstein-Friesian okse (1606 Frasse) i 1970 årene. Storskala resekvensering tillot molekylær karakterisering av haplotypen fra 1606 Frasse, og sannsynlige kausale polymorfismer ble detektert i promotor regionen og i den 5’- flankerende utranslaterte regionen av genet CSN1S2.Norges Forskningsråd ; Geno Breeding and AI Association ; BoviBank Lt

Helserelatert livskvalitet til pasienter som er operert for prostatakreft.

Videreutdanning i kreftsykepleieInnledning: Prostatakreft er den vanligste kreftformen blant menn i Norge. Operasjon av prostatakreft kan gi bivirkninger i form av urininkontinens og/eller impotens. Omtrent 50% av de som gjennomfører radikal prostatectomi blir impotente (Tandstad & Klepp, 2020, s. 297). Tallene viser at prosenten er høy, og det er viktig å få mer kunnskap om hvordan mennene opplever sin helse relaterte livskvalitet (HRLK) etter operasjon. Problemstilling: Litteraturstudien er basert på helserelatert livskvalitet. Problemstillingen innebærer å se nærmere på hvordan identitet, kroppslig og psykisk helse blir påvirket av radikal prostatectomi og laparoskopisk radikal prostatectomi. Problemstillingen til studien er «Hvordan opplever menn over 45 år sin helserelaterte livskvalitet etter operasjon for prostatakreft?» Metode: Litteraturstudien inkluderer både kvantitative og kvalitative studier, og innebærer en tematisk analyse (Dalland, 2020, s. 96–97). Jeg har benyttet meg av en hermeneutisk tilnærming, der jeg har fokusert på resultat- og diskusjonsdelen i artiklene. Resultater: Resultatene er tolket fra åtte artikler. Gjennom tematisk analyse kom jeg frem til tre hovedtemaer som omhandler HRLK, identitet, kroppslig og psykisk helse. Hovedfunnene i artiklene var ofte at mennene opplevde impotens, seksual dysfunksjon, urininkontinens og følte seg mindre mannlige. God oppfølging fra helsevesenet kan være en positiv bidragsyter til HRLK. Konklusjon: Operasjon for prostatakreft gir ofte negative følger til HRLK. God tverrfaglig postoperativ individuell oppfølging kan bidra til å snu de negative følgene til noe positivt

Can we rely on selected genetic markers for population identification? Evidence from coastal Atlantic cod

The use of genetic markers under putative selection in population studies carries the potential for erroneous identification of populations and misassignment of individuals to population of origin. Selected markers are nevertheless attractive, especially in marine organisms that are characterized by weak population structure at neutral loci. Highly fecund species may tolerate the cost of strong selective mortality during early life stages, potentially leading to a shift in offspring genotypes away from the parental proportions. In Atlantic cod, recent genetic studies have uncovered different genotype clusters apparently representing phenotypically cryptic populations that coexist in coastal waters. Here, we tested if a high‐graded SNP panel specifically designed to classify individual cod to population of origin may be unreliable because of natural selection acting on the SNPs or their linked background. Temporal samples of cod were collected from two fjords, starting at the earliest life stage (pelagic eggs) and carried on until late autumn (bottom‐settled juveniles), covering the period during summer of high natural mortality. Despite the potential for selective mortality during the study period, we found no evidence for selection, as both cod types occurred throughout the season, already in the earliest egg samples, and there was no evidence for a shift during the season in the proportions of one or the other type. We conclude that high‐graded marker panels under putative natural selection represent a valid and useful tool for identifying biological population structure in this highly fecund species and presumably in others.publishedVersio

Virker prestasjonsbasert lønn prestasjonsfremmende – og eventuelt hvilke andre faktorer påvirker prestasjon hos medarbeidere?

Flere norske bedrifter benytter prestasjonsbasert lønn i lønnsmodellen sin. Den vanligste formen er bonus, og en stor andel av privat sektor benytter en eller annen form for prestasjonsbasert lønn. Formålet med studien er å få en forståelse for hvordan prestasjonsbasert lønn påvirker prestasjoner og hvilke forutsetninger som må ligge til rette for at dette incentivsystemet skal virke effektivt. Problemstillingen er som følger: Virker prestasjonsbasert lønn prestasjonsfremmende – og eventuelt hvilke andre faktorer påvirker prestasjon hos medarbeidere? For å undersøke problemstillingen benyttet vi en kvalitativ tilnærming, der vi intervjuet fire personer fra fire ulike bedrifter. Intervjuforberedelsene gikk ut på å finne relevante teorier og tidligere forskning om prestasjonslønn. Vi har benyttet teorier om prestasjonsbasert lønn, atferd og motivasjon. Funn viser at ulike lønnsmodeller kan være effektive gitt en rekke forutsetninger. Prestasjonsbasert lønn ser ut til å fungere gitt forutsetninger som at det er en god balanse mellom indre og ytre motivasjon, at lønnsmodellen oppleves rettferdig og at det er godt samhold i bedriften. Funnene viser at lønnens betydning varierer fra bransje til bransje, og det er derfor viktig å tilpasse lønnsmodellen etter bedriftens strategiske mål og arbeidsoppgaver.Several Norwegian companies use performance-related pay in their pay model. The most common form of performance-related pay is bonus, and a large proportion of the private sector uses some form of performance-related pay. The purpose of the thesis is to gain an understanding of how performance-related pay affects performance and what factors is required for this incentive system to work effectively. The thesis questions are as follows: Does performance-related pay promote performance – and what other factors affect performance among employees? To investigate the thesis question, we used a qualitative approach, where we interviewed four people from four different companies. The interview preparations consisted of finding relevant theories and previous research on performance-related pay. We have used theories about performance-related pay, behavior, and motivation. Findings show that different pay models can be effective given several assumptions. Performance-related pay seems to work given that factors such as a good balance between internal and external motivation, the perception that the pay model is fair and the feeling of belonging. The findings show that the importance of pay varies from industry to industry, and it is therefore important to adapt the pay model to the company's strategic goals and work tasks

Virker prestasjonsbasert lønn prestasjonsfremmende – og eventuelt hvilke andre faktorer påvirker prestasjon hos medarbeidere?

Flere norske bedrifter benytter prestasjonsbasert lønn i lønnsmodellen sin. Den vanligste formen er bonus, og en stor andel av privat sektor benytter en eller annen form for prestasjonsbasert lønn. Formålet med studien er å få en forståelse for hvordan prestasjonsbasert lønn påvirker prestasjoner og hvilke forutsetninger som må ligge til rette for at dette incentivsystemet skal virke effektivt. Problemstillingen er som følger: Virker prestasjonsbasert lønn prestasjonsfremmende – og eventuelt hvilke andre faktorer påvirker prestasjon hos medarbeidere? For å undersøke problemstillingen benyttet vi en kvalitativ tilnærming, der vi intervjuet fire personer fra fire ulike bedrifter. Intervjuforberedelsene gikk ut på å finne relevante teorier og tidligere forskning om prestasjonslønn. Vi har benyttet teorier om prestasjonsbasert lønn, atferd og motivasjon. Funn viser at ulike lønnsmodeller kan være effektive gitt en rekke forutsetninger. Prestasjonsbasert lønn ser ut til å fungere gitt forutsetninger som at det er en god balanse mellom indre og ytre motivasjon, at lønnsmodellen oppleves rettferdig og at det er godt samhold i bedriften. Funnene viser at lønnens betydning varierer fra bransje til bransje, og det er derfor viktig å tilpasse lønnsmodellen etter bedriftens strategiske mål og arbeidsoppgaver.Several Norwegian companies use performance-related pay in their pay model. The most common form of performance-related pay is bonus, and a large proportion of the private sector uses some form of performance-related pay. The purpose of the thesis is to gain an understanding of how performance-related pay affects performance and what factors is required for this incentive system to work effectively. The thesis questions are as follows: Does performance-related pay promote performance – and what other factors affect performance among employees? To investigate the thesis question, we used a qualitative approach, where we interviewed four people from four different companies. The interview preparations consisted of finding relevant theories and previous research on performance-related pay. We have used theories about performance-related pay, behavior, and motivation. Findings show that different pay models can be effective given several assumptions. Performance-related pay seems to work given that factors such as a good balance between internal and external motivation, the perception that the pay model is fair and the feeling of belonging. The findings show that the importance of pay varies from industry to industry, and it is therefore important to adapt the pay model to the company's strategic goals and work tasks

Molecular characterization of a long range haplotype affecting protein yield and mastitis susceptibility in Norwegian Red cattle

<p>Abstract</p> <p>Background</p> <p>Previous fine mapping studies in Norwegian Red cattle (NRC) in the region 86-90.4 Mb on <it>Bos taurus </it>chromosome 6 (BTA6) has revealed a quantitative trait locus (QTL) for protein yield (PY) around 88 Mb and a QTL for clinical mastitis (CM) around 90 Mb. The close proximity of these QTLs may partly explain the unfavorable genetic correlation between these two traits in NRC. A long range haplotype covering this region was introduced into the NRC population through the importation of a Holstein-Friesian bull (1606 Frasse) from Sweden in the 1970s. It has been suggested that this haplotype has a favorable effect on milk protein content but an unfavorable effect on mastitis susceptibility. Selective breeding for milk production traits is likely to have increased the frequency of this haplotype in the NRC population.</p> <p>Results</p> <p>Association mapping for PY and CM in NRC was performed using genotypes from 556 SNPs throughout the region 86-97 Mb on BTA6 and daughter-yield-deviations (DYDs) from 2601 bulls made available from the Norwegian dairy herd recording system. Highest test scores for PY were found for single-nucleotide polymorphisms (SNPs) within and surrounding the genes <it>CSN2 </it>and <it>CSN1S2</it>, coding for the β-casein and α_S2-casein proteins. High coverage re-sequencing by high throughput sequencing technology enabled molecular characterization of a long range haplotype from 1606 Frasse encompassing these two genes. Haplotype analysis of a large number of descendants from this bull indicated that the haplotype was not markedly disrupted by recombination in this region. The haplotype was associated with both increased milk protein content and increased susceptibility to mastitis, which might explain parts of the observed genetic correlation between PY and CM in NRC. Plausible causal polymorphisms affecting PY were detected in the promoter region and in the 5'-flanking UTR of <it>CSN1S2</it>. These polymorphisms could affect transcription or translation of <it>CSN1S2 </it>and thereby affect the amount of α_S2-casein in milk.</p> <p>Highest test scores for CM were found in the region 89-91 Mb on BTA6, very close to a cluster of genes coding for CXC chemokines. Expression levels of some of these CXC chemokines have previously been shown to increase in bovine mammary gland cell lines after exposure to bacterial cell wall components.</p> <p>Conclusion</p> <p>Molecular characterization of the long range haplotype from the Holstein-Friesian bull 1606 Frasse, imported into NRC in the 1970s, revealed polymorphisms that could affect transcription or translation of the casein gene <it>CSN1S2</it>. Sires with this haplotype had daughters with significantly elevated milk protein content and selection for milk production traits is likely to have increased the frequency of this haplotype in the NRC population. The haplotype was also associated with increased mastitis susceptibility, which might explain parts of the genetic correlation between PY and CM in NRC.</p

Mixed origin of juvenile Atlantic cod (Gadus morhua) along the Swedish west coast

Cryptic population structure in exploited fishes poses a major challenge for fisheries management. In Atlantic cod, sympatric ecotypes are well-known, for instance off the coast of northern Norway. Recently, two sympatric cod ecotypes have also been documented in the Skagerrak and Kattegat, where adult cod has declined dramatically. One ecotype has an apparent offshore origin and displays a more migratory lifestyle than the other, which is generally resident at the coast throughout its life. To investigate their relative abundances along the Swedish west coast, juvenile cod were collected at high spatial resolution along the coast and genetically assigned to ecotypes. The results reveal large proportions of the coastal ecotype in the southern Kattegat, Öresund, and inshore Swedish Skagerrak, whereas the offshore ecotype dominates in offshore areas. A regression model comparison suggests that differences in bottom depth, rather than distance from the open sea, explain the heterogeneous spatial distribution of the two ecotypes. In addition, the two ecotypes display genetic differences suggesting adaptation to different environments. The results underline that successful fisheries management requires identification and consideration of locally adapted sympatric ecotypes.publishedVersio

Mixed origin of juvenile Atlantic cod (Gadus morhua) along the Swedish west coast

Cryptic population structure in exploited fishes poses a major challenge for fisheries management. In Atlantic cod, sympatric ecotypes are well-known, for instance off the coast of northern Norway. Recently, two sympatric cod ecotypes have also been documented in the Skagerrak and Kattegat, where adult cod has declined dramatically. One ecotype has an apparent offshore origin and displays a more migratory lifestyle than the other, which is generally resident at the coast throughout its life. To investigate their relative abundances along the Swedish west coast, juvenile cod were collected at high spatial resolution along the coast and genetically assigned to ecotypes. The results reveal large proportions of the coastal ecotype in the southern Kattegat, Öresund, and inshore Swedish Skagerrak, whereas the offshore ecotype dominates in offshore areas. A regression model comparison suggests that differences in bottom depth, rather than distance from the open sea, explain the heterogeneous spatial distribution of the two ecotypes. In addition, the two ecotypes display genetic differences suggesting adaptation to different environments. The results underline that successful fisheries management requires identification and consideration of locally adapted sympatric ecotypes.publishedVersionPaid open acces

Local recruitment of Atlantic cod and putative source spawning areas in a coastal seascape

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Genomic and functional gene studies suggest a key role of beta-carotene oxygenase 1 like (bco1l) gene in salmon flesh color

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