Signals of selection and the genetic basis of milk production in cattle

Domesticated species such as cattle have evolved under natural and artificial selection, leading to cattle breeds (both Bos taurus and Bos indicus) that display a broad phenotypic spectrum. As a result of intensive artificial selection together with artificial insemination, highly productive global cattle breeds have been developed that are replacing local, native cattle breeds. This study focuses on analyses of how selection has modified the genomes of different cattle populations having diverse breeding histories, especially with regard to milk production and adaptation. For that, both gene and genome level studies were conducted. The molecular architecture of two quantitative trait loci (QTL) was investigated in different species and breeds using two candidate genes for milk yield, GHR and PRLR. The intracellular parts of the two genes were sequenced from over 10 cattle breeds and from different Artiodactyla species. The study revealed divergent selection pressures on GHR and PRLR genes among Artiodactyl species. The GHR gene was more divergent within genus Bos than between different species among the Bovinae linage. Nonsynonymous mutations have accumulated in the PRLR gene in pigs, possibly implying that PRLR has been either target of directional or artificial selection in pigs. SNP markers covering the whole genome at medium density were used to search for effects of artificial selection in different types of cattle breeds and to compare the genetic relatedness of differently selected breeds. This revealed evidences that GHR gene has been a target of selection in certain cattle breeds. In addition, several other genomic regions were found to be targets of selection. Most of them were not shared between the breeds but a region on chromosome 16 was found to be under selection in six breeds. Clear genetic separation between the turano-mongolicus type breed and other Bos taurus breeds was found by both whole genome SNP data and the GHR gene sequence. The within breed diversity was relatively similar for all breeds even if the histories of the studied breeds varied substantially. The estimates of effective population sizes calculated from whole genome SNP data varied from extremely low (24) to moderately high (150). In the last stage of the study, whole genome sequences were used for genome-wide association study (GWAS) to find genomic regions affecting milk, protein and fat yield in Nordic dairy cattle. The association study confirmed the existence of milk QTL on cattle chromosome 20, at the GHR gene, whereas no support for the QTL at PRLR gene was gained. Several thousand additional candidate SNPs with effect on milk production were located from eight cattle chromosomes. However, establishing the true causative variant remains challenging even when the densest possible marker map is used because of linkage disequilibrium. Taken together, this thesis provides genetic information from various Northern Eurasian cattle breeds that can be used for example for conservation decisions and gives a map of selection signatures for them. These selected genome regions may contain variation that would provide valuable traits for changing climate conditions. The knowledge of the genetic background of milk production and the effect of artificial selection is essential when breeding organizations are making decisions how to maintain and improve their genetic material.Valinnan jalanjäljet ja maidontuotannon geneettinen tausta naudalla Ihmisen tekemä valinta yhdessä luonnonvalinnan kanssa on johtanut nautarotuihin, joiden ulkoasut vaihtelevat suuresti. Intensiivinen jalostusvalinta yhdessä keinosiemennyksen käyttöönoton kanssa on johtanut korkeatuottoisten rotujen maailmanlaajuiseen menestymiseen paikallisten nautarotujen kustannuksella. Tässä väitöskirjatyössä tutkittiin, kuinka valinta on vaikuttanut eri tavalla jalostettujen nautarotujen perimään, erityisesti keskittyen maidontuotantoon ja adaptaatioon. Ensimmäisessä vaiheessa tutkittiin kahden kvantitatiivisiin ominaisuuksiin vaikuttavan lokuksen (QTL) molekyylirakennetta. Kahden maidontuotantoon vaikuttavan kandidaattigeenin, kasvuhormonireseptorin (GHR) ja prolaktiinireseptorin (PRLR) solunsisäisen osan koodaava alue sekvensoitiin eri tavalla jalostetuilta nautaroduilta sekä verrattiin saatuja sekvenssejä eri sorkkaeläinlajien vastaaviin sekvensseihin. Valintapaineen todettiin olleen erilainen näissä kahdessa geenissä, GHR geeni oli muuntelultaan rikkaampaa Bos suvun sisällä kuin lajien välillä Bovinae linjassa. Työssä selvitettiin, että sioilla PRLR geeniin on kerääntynyt useita aminohappomuutokseen johtavia mutaatioita, toisin kuin naudoilla. Sioilla PRLR geeni onkin voinut olla joko suoran tai ihmisen suorittaman jalostusvalinnan kohde. Valinnan jalanjälkiä haettiin koko perimän kattavasta SNP-merkkiaineistosta käyttäen eri tavalla jalostettuja nautarotuja. Samaa aineistoa käytettiin nautarotujen geneettisen rakenteen selvittämiseen. Tässä työssä pystyttiin osoittamaan, että GHR geeni on ollut valinnan kohteena tietyissä nautaroduissa. Lisäksi löydettiin useita muita perimän alueita, joihin on kohdistunut valintaa. Useimmat alueista eivät ole samoja eri rotujen kesken, mutta naudan kromosomissa 16 on mielenkiintoinen alue, jonka osoitettiin olleen valinnan kohteena kuudessa eri rodussa. Työssä todettiin turano-mongolicus alatyyppiin kuuluvan nautarodun eroavan selvästi geneettisesti muista Bos taurus -tyyppisistä naudoista. Rotujen sisäisen geneettisen monimuotoisuuden todettiin olevan suhteellisen samanlaista, vaikka tutkittujen rotujen jalostushistoriat poikkeavatkin merkittävästi toisistaan. Teholliset populaatiokoot vaihtelivat nautarotujen välillä äärimmäisen alhaisesta (24) kohtalaisen korkeaan (150). Viimeisessä vaiheessa koko perimän sekvenssien perusteella määritettyjä variaatioita käytettiin assosiaatiokartoituksessa, jonka avulla paikannettiin maito-, rasva- ja proteiinimääriin vaikuttavia perimän alueita pohjoismaisessa punaisessa lypsyrodussa. Tutkimus vahvisti GHR geenin olevan erittäin vahva kandidaatti havaitulle QTL vaikutukselle kromosomissa 20 kun taas PRLR geenistä vastaavaa ei todettu. Lisäksi löydettiin useita tuhansia maitotuotokseen assosioituneita SNP-merkkejä yhteensä kahdeksasta eri kromosomista. Vaikka käytössä oli teoreettisesti kaikki mahdolliset variaatiot naudan perimästä, kausatiivisen variaation tunnistaminen on haastavaa johtuen variaatioiden välisestä kytkentäepätasapainosta. Yhteenvetona voidaan sanoa, että tutkimus tuo lisätietoa pohjoisen Euraasian nautarotujen geneettisestä taustasta mahdollisten suojelupäätösten tueksi ja antaa pohjan valinnan jalanjälkien tarkempaan tutkimukseen näillä roduilla. Eläinten geneettisten resurssien kartoittaminen on erityisen tärkeää muuttuvissa ilmasto-olosuhteissa. Maidontuotannon geneettisten taustojen selvittäminen on tärkeää jalostusohjelmissa ja tietoa voidaan käyttää jalostussuunnitelmien tukena.Siirretty Doriast

Kesytys ja jalostus muokanneet naudan perimää

Näytä koko lehti</a

A microsatellite-based analysis for the detection of selection on BTA1 and BTA20 in northern Eurasian cattle (Bos taurus) populations

<p>Abstract</p> <p>Background</p> <p>Microsatellites surrounding functionally important candidate genes or quantitative trait loci have received attention as proxy measures of polymorphism level at the candidate loci themselves. In cattle, selection for economically important traits is a long-term strategy and it has been reported that microsatellites are linked to these important loci.</p> <p>Methods</p> <p>We have investigated the variation of seven microsatellites on BTA1 (<it>Bos taurus </it>autosome 1) and 16 on BTA20, using bovine populations of typical production types and horn status in northern Eurasia. Genetic variability of these loci and linkage disequilibrium among these loci were compared with those of 28 microsatellites on other bovine chromosomes. Four different tests were applied to detect molecular signatures of selection.</p> <p>Results</p> <p>No marked difference in locus variability was found between microsatellites on BTA1, BTA20 and the other chromosomes in terms of different diversity indices. Average <it>D</it>' values of pairwise syntenic markers (0.32 and 0.28 across BTA 1 and BTA20 respectively) were significantly (<it>P </it>< 0.05) higher than for non-syntenic markers (0.15). The Ewens-Watterson test, the Beaumont and Nichol's modified frequentist test and the Bayesian <it>F</it>_ST-test indicated elevated or decreased genetic differentiation, at <it>SOD1 </it>and <it>AGLA17 </it>markers respectively, deviating significantly (<it>P </it>< 0.05) from neutral expectations. Furthermore, lnRV, lnRH and lnRθ' statistics were used for the pairwise population comparison tests and were significantly less variable in one population relative to the other, providing additional evidence of selection signatures for two of the 51 loci. Moreover, the three Finnish native populations showed evidence of subpopulation divergence at <it>SOD1 </it>and <it>AGLA17</it>. Our data also indicate significant intergenic linkage disequilibrium around the candidate loci and suggest that hitchhiking selection has played a role in shaping the pattern of observed linkage disequilibrium.</p> <p>Conclusion</p> <p>Hitchhiking due to tight linkage with alleles at candidate genes, e.g. the <it>POLL </it>gene, is a possible explanation for this pattern. The potential impact of selective breeding by man on cattle populations is discussed in the context of selection effects. Our results also suggest that a practical approach to detect loci under selection is to simultaneously apply multiple neutrality tests based on different assumptions and estimations.</p

Identification of copy number variations and candidate genes for reproduction traits in Finnish pig populations

Animal breeding programs can be improved by genetic markers associated with production and reproduction traits. Reproduction traits are important for economic success of pig production and therefore development of genetic tools for selection is of high interest to pig breeding. In this study our objective was to identify genomic regions as-sociated with fertility traits in two Finnish pig breeds using large scale SNP genotyping and genome wide association analysis and characterization of copy number variations (CNV). Since CNVs are structural variations of the genome they potentially have a large effect on gene expression and protein function. We analyzed 1265 genotyped boars for nine different reproduction traits and identified 46 CNV regions encompassing 13 genes. 11 of the CNV regions were shared between the breeds, 20 were unique to the Finnish Yorkshire and 15 to the Finnish Landrace. The ge-nome wide association (GWAS) analysis identified zero to five reproduction associated genomic regions per trait. Furthermore, we identified 23 genomic regions with 20 candidate genes associated with fertility traits using GWAS analysis. The identified CNV regions were compared against GWAS regions to detect candidate regions with an ef-fect on reproduction traits. This study reports candidate genes and genomic regions within two Finnish pig breeds for reproduction traits, which can be utilized in breeding programs.Peer reviewe

Clinical and nutritional biomarkers - tools to verify effects of personal APOE gene risk status information and health guidance intervention

201

Mitochondrial DNA and Y-chromosomal diversity in ancient populations of domestic sheep (Ovis aries) in Finland : comparison with contemporary sheep breeds

201

Suomenkarjan erityisominaisuudet hyötykäyttöön

Selvitys apurahan käytöstä Suomen Kulttuurirahastolle, 5.3.2013 LOPPURAPORTT

Temporal Fluctuation in North East Baltic Sea Region Cattle Population Revealed by Mitochondrial and Y-Chromosomal DNA Analyses

Background Ancient DNA analysis offers a way to detect changes in populations over time. To date, most studies of ancient cattle have focused on their domestication in prehistory, while only a limited number of studies have analysed later periods. Conversely, the genetic structure of modern cattle populations is well known given the undertaking of several molecular and population genetic studies. Results Bones and teeth from ancient cattle populations from the North-East Baltic Sea region dated to the Prehistoric (Late Bronze and Iron Age, 5 samples), Medieval (14), and Post-Medieval (26) periods were investigated by sequencing 667 base pairs (bp) from the mitochondrial DNA (mtDNA) and 155 bp of intron 19 in the Y-chromosomal UTY gene. Comparison of maternal (mtDNA haplotypes) genetic diversity in ancient cattle (45 samples) with modern cattle populations in Europe and Asia (2094 samples) revealed 30 ancient mtDNA haplotypes, 24 of which were shared with modern breeds, while 6 were unique to the ancient samples. Of seven Y-chromosomal sequences determined from ancient samples, six were Y2 and one Y1 haplotype. Combined data including Swedish samples from the same periods (64 samples) was compared with the occurrence of Y-chromosomal haplotypes in modern cattle (1614 samples). Conclusions The diversity of haplogroups was highest in the Prehistoric samples, where many haplotypes were unique. The Medieval and Post-Medieval samples also show a high diversity with new haplotypes. Some of these haplotypes have become frequent in modern breeds in the Nordic Countries and North-Western Russia while other haplotypes have remained in only a few local breeds or seem to have been lost. A temporal shift in Y-chromosomal haplotypes from Y2 to Y1 was detected that corresponds with the appearance of new mtDNA haplotypes in the Medieval and Post-Medieval period. This suggests a replacement of the Prehistoric mtDNA and Y- chromosomal haplotypes by new types of cattle.Peer reviewe

A frameshift mutation in ARMC3 is associated with a tail stump sperm defect in Swedish Red (Bos taurus) cattle

Background: Artificial insemination is widely used in many cattle breeding programs. Semen samples of breeding bulls are collected and closely examined immediately after collection at artificial insemination centers. Only ejaculates without anomalous findings are retained for artificial insemination. Although morphological aberrations of the spermatozoa are a frequent reason for discarding ejaculates, the genetic determinants underlying poor semen quality are scarcely understood. Results: A tail stump sperm defect was observed in three bulls of the Swedish Red cattle breed. The spermatozoa of affected bulls were immotile because of severely disorganized tails indicating disturbed spermatogenesis. We genotyped three affected bulls and 18 unaffected male half-sibs at 46,035 SNPs and performed homozygosity mapping to map the fertility disorder to an 8.42 Mb interval on bovine chromosome 13. The analysis of whole-genome re-sequencing data of an affected bull and 300 unaffected animals from eleven cattle breeds other than Swedish Red revealed a 1 bp deletion (Chr13: 24,301,425 bp, ss1815612719) in the eleventh exon of the armadillo repeat containing 3-encoding gene (ARMC3) that was compatible with the supposed recessive mode of inheritance. The deletion is expected to alter the reading frame and to induce premature translation termination (p.A451fs26). The mutated protein is shortened by 401 amino acids (46 %) and lacks domains that are likely essential for normal protein function. Conclusions: We report the phenotypic and genetic characterization of a sterilizing tail stump sperm defect in the Swedish Red cattle breed. Exploiting high-density genotypes and massive re-sequencing data enabled us to identify the most likely causal mutation for the fertility disorder in bovine ARMC3. Our results provide the basis for monitoring the mutated variant in the Swedish Red cattle population and for the early identification of infertile animals.Peer reviewe

A 660-Kb deletion with antagonistic effects on fertility and milk production segregates at high frequency in Nordic Red cattle : additional evidence for the common occurrence of balancing selection in livestock

201