Auswahl der wissenschaftlichen Literatur zum Thema „Merino sheep Australia Genetics“

Muscular dystrophies (MDs) are neuromuscular disorders characterised by chronic, usually progressive, skeletal muscle weakness. Individuals often lose walking ability and can suffer terminal cardiorespiratory complications. Determining the genetics of a disease helps provide diagnosis, prognosis, genetic counselling, and the basis for rational therapeutic design. A naturally occurring sheep model of autosomal recessive congenital MD was identified in WA in the 1950’s and preserved as a research colony. The pathological features and distribution of this MD is novel. A sheep model of MD is incredibly valuable; sheep have similar skeletal muscle mass to humans, representing a significant improvement over smaller mammals in which to trial therapies. Successfully characterising the causative gene(s) would enable a possible target for new therapies and may open new lines of investigation into better understanding and treatment of MD in humans. This project utilised a two-pronged approach to investigate the genetics of this ovine MD. First, bioinformatics analysis of SNP genotyping for multiple individuals in the flock by a 50,000 SNP array in combination with the latest sheep genome reference build released by the International Sheep Genome Consortium, enabling homozygosity mapping, genetic linkage and association mapping. Second, molecular biological approaches further explored the identified prime candidate gene by cDNA sequencing. This research project identified ROCK2 as the prime candidate gene most likely harbouring a mutation causing the muscular dystrophy in this internationally unique ovine model. It also demonstrated for the first time in sheep the existence of ROCK2m, an isoform of ROCK2 preferentially expressed in skeletal muscle. This work has set the stage for further investigations into ROCK2m and the ovine MD which will hopefully pinpoint the causative disease mutation.

Wool from Merino sheep is an important component of the Australian economy. However, little is known of the mechanisms within the wool follicle that regulate fibre production. The aim of the research described here was to identify and characterise some of the genes expressed in the follicle.A highly expressed gene has been identified from skin and sequenced. The information obtained on this gene suggests that it might be of use in future transgenic studies. Two cDNA libraries were constructed. The first was constructed using small amounts of total RNA from skin and PCR methodology, following a published method. A second cDNA library was then produced from adult mid-flank skin using a commercially available kit. A pool of 420 potential wool follicle specific transcripts were identified from this adult mid-flank skin cDNA library using a combination of differential and subtractive screening. Clone 1-25 was chosen as the focus for the remaining work described in this thesis. Expression of clone 1-25 was detected at all stages of wool follicle development and was localised to the wool follicle bulb, inner root sheath, outer root sheath, epidermis, but not the dermis or dermal papilla. The function of clone 1-25 is as yet unknown. However, from its expression in the wool follicle, and studies by other groups, it appears that it may play a role in inducing differentiation
Doctor of Philosophy (PhD) (Biological Sciences)

A candidate gene approach was used to identify potential genetic markers associated with wool quality traits including mean fibre diameter (MFD), fibre diameter standard deviation (FDSD), coefficient of variation of fibre diameter (CVD), prickle factor, curvature, yellowness, brightness, staple strength, staple length, yield, greasy fleece weight (GFW) and clean fleece weight (CFW). Inheritance of potential genetic markers was studied in two half-sib Merino families and assessed for association with the wool quality traits. The sire for one of the half-sib families is referred to as MV144-58-00, and wool measurements from its progeny were taken at 12 (n = 131), 24 (n =128) and 36 (n = 37) months of age. The sire for the second half-sib family is referred to as Stoneyhurst, and wool measurements from its progeny (n = 35) were taken at 12 months of age. Genes that code for the keratin intermediate-filament proteins (KRTs) (KRT1.2, KRT2.10) and the keratin intermediate-filament-associated proteins (KAPs) (KAPl.1, KAPl.3, KAP3.2, KAP6.1, KAP 7, KAP8) were targeted for this investigation, along with the beta 3-adrenergic receptor (ADRB3) gene and microsatellites BfMS and OarFCB193. Polymerase chain reaction (PCR) was used to amplify specific DNA fragments from each locus and PCR- single strand conformational polymorphism (PCR-SSCP) analysis was used to detect polymorphism within the half-sib families for all the loci, except for the KAP1.1 gene, where length polymorphism was detected using agarose gel electrophoresis. Only the loci that were heterozygous for the sire (KAP1.1, KAP1.3, KRT1.2, ADRB3, KAP8) and hence were informative, were genotyped in the progeny. The total number of alleles observed at the KAP1.1, KAP1.3, KRT1.2, KAP8 and the ADRB3 loci were four, ten, six, five and six, respectively. Analysis of each of the informative loci revealed allelic associations with various wool traits. In the MV144-58-00 (genotypes KAP1.1 AB; KAP1.3 BD; KRT1.2 AB; ADRB3 CE) half-sib, inheritance of the KAP1.1 A allele was associated with a higher yield at 24 months of age (P = 0.037). This trend also observed at 36 months of age (P = 0.078). At 12 months of age, the KAP1.1 A allele tended to be associated with increased staple length (P = 0.08). At 36 months of age, the inheritance of the KAP1.1 B allele tended towards being associated with whiter wool (P = 0.080). The MV144-58-00 KAP1.3 D allele tended to be associated with increased yield at 24 and 36 months of age (P = 0.091 and 0.059, respectively), and with lower FDSD at 12 months of age (P = 0.055). The sire KAP1.3 B allele was associated with whiter wool colour at 36 months of age (P = 0.045). The inheritance of the MV144-58-00 KR T1.2 B allele was associated with or tended to be associated with a smaller FDSD (P = 0.040), an increase in staple strength (P = 0.025) and an increase in GFW (P = 0.069) at 12 months of age. At 24 months of age, the KR T1.2 B allele tended to be associated with increased yield (P = 0.057). At 36 months of age, the KRTl.2 A allele was associated with whiter wool (P = 0.019) and tended to be associated with increased crimp within the wool fibre (P = 0.089). In the Stoneyhurst (genotypes KAP1.1 BC; KAP1.3 CJ; KRT1.2 DE; ADRB3 CE) half-sib, inheritance of the KAP1.1 B allele was associated with longer staple length (P = 0.018) and a decrease in wool brightness (P = 0.039). In contrast, KAP1.1 C allele was associated with lowest staple length (P = 0.018) and brighter wool colour (P = 0.039). Associations observed with the inheritance of Stoneyhurst KAP 1.1 alleles were similar to the inheritance ofKAPl.3 alleles. Stoneyhurst KAP1.3 J allele was associated with longer staple length (P = 0.017) and a decrease in wool brightness (P = 0.010). In contrast, KAP1.3 C allele was associated with lowest staple length (P = 0.017) and brighter wool colour (P = 0.010). The Stoneyhurst KRT12 D allele was associated with longer staple length and a decrease in wool brightness (P = 0.033). In contrast, KRT1.2 E allele was associated with lowest staple length (P = 0.033) and brighter wool colour (P = 0.022). Sire alleles at the ADRB3 gene locus were associated with variation in staple strength (P = 0.025) for MV144-58-00's progeny, and with variation in yield (P = 0.023) for Stoneyhurst's progeny. The results obtained in this thesis are consistent with KAP1.1, KAP1.3 and KRT1.2 being clustered on one chromosome because both sires in this study passed on two major KAP1.1-KAP1.3-KRT1.2 haplotypes to their progeny, and the associations with wool traits were very similar for all the three loci. The major sire derived KAP1.1 – KAP1.3 - KRT1.2 haplotypes observed within the MV144-58-00 half-sib were: BBA (frequency of 43.4%; n = 43) and ADB (frequency of 44.4%; n = 44). Other minor haplotypes observed were: ADA (frequency of 4.0%; n = 4); BDA (frequency of 2.0%; n = 2); BBB (frequency of 3.0%; n = 3) and BDB (frequency of 3.0%; n = 3). In the Stoneyhurst half-sib, major sire-derived KAP 1.1 - KAP 1.3 - KR Tl.2 haplotypes observed were CCE (frequency of 53.1 %; n = 17) and BJD (frequency of 40.6%; n = 13). The minor haplotype BJE (frequency of 6.3%; n = 2) was also observed. Statistical analyses within the MVI44-58-00 half-sib showed that KAP1.1 AKAP1.3 D - KRT1.2 B haplotype was associated with increased yield (P = 0.023) and tended towards whiter wool colour (P = 0.059), smaller FDSD (P = 0.081) and stronger staple strength (P = 0.092). In the Stoneyhurst half-sib, the KAP1.1 B - KAP1.3 J - KRT1.2 D haplotype was associated with longer staple length (P = 0.010), while the KAP1.1 C - KAP1.3 C - KRT1.2 E haplotype showed a strong trend with increased wool brightness (P = 0.096). Result from this study indicated that the keratin genes on chromosome 11 are recombining relatively frequently at recombination "hotspots". A high rate of recombination among loci that impact on wool traits would make breeding for consistent wool quality very difficult. The results presented in this thesis suggest that genes coding for the KRTs and KAPs have the potential to impact on wool quality. KAP1.1, KAP1.3 and KRT1.2 could potentially be exploited in gene marker-assisted selection programmes within the wool industry to select for animals with increased staple length, 'increased staple strength, higher yield and brighter wool. This study was however limited to two half-sib families, and further investigation is required.

Thesis (MScAgric)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Genetic (co)variances for body weight, clean fleece weight and fibre diameter were estimated for the South African Dohne Merino using data transformed as proportions of contemporary group means. The data analysed included body weight, clean fleece weight and fibre diameter records for 282 513 animals, evaluated between 1992 and 2011. There were 5 698 sires, 105 886 dams and 6 291 contemporary groups in the data. A three-trait animal model was fitted, where the random variables were the direct additive genetic effects, as well as the sire-flock-season (SFS) interaction, while the fixed effects included contemporary groups (FYSSM) (6 291 classes), birth status (single, twins or triplets), age of dam (1 to 3 years), which was plotted as a linear regression as well as age at performance measurement, which was fitted as a polynomial. The direct heritability estimates (SE) for body weight, clean fleece weight and fibre diameter were 0.265 (0.005), 0.210 (0.004) and 0.437 (0.005), respectively. Genetic correlations for body weight with clean fleece weight and fibre diameter were 0.035 (0.015) and 0.139 (0.011), respectively, while the genetic correlation between clean fleece weight and fibre diameter was 0.169 (0.012). Body weight had phenotypic correlations of 0.327 (0.002) and 0.150 (0.002), respectively, with clean fleece weight and fibre diameter, which had a phenotypic correlation of 0.190 (0.002) with clean fleece weight. The moderate to high heritability estimates suggests that there is substantial genetic variation, which may result in genetic improvement if selection is applied on these traits. Genetic correlations were generally low, suggesting that progress in all these traits was possible in a scientific selection program. Genetic trends derived during the study supported the contention that genetic progress in all traits was attainable in a well-constructed breeding programme. Transformation of the data to percentages of contemporary groups resulted in adjustments to breeding values. The breeding values for sires originating from flocks maintained in limiting environments (Low group; 180 sires) were adjusted upwards, while those of sires originating from a non-limiting production environment (High group; 146 sires) were adjusted downwards. These effects were markedly obvious for the quantitative traits (body weight and clean fleece weight), but to a much lesser extent for fibre diameter. This transformation resulted in the genetic trends for the Low groups being adjusted to be comparable to those in the High group for body weight and Fibre diameter. It was concluded that sire breeding values derived from transformed data would be more robust across the typical diverse environments supporting local Dohne Merino production. The genetic value of animals entering the recorded population from a commercial base (F4 animals) was below the fully recorded part of the population. The inclusion of phantom parent groups in the genetic analysis rendered genetic trends in F4 animals comparable to that of the pedigreed portion of animals in the analyses. It was concluded that animals from a commercial base (which are alleged to have advantages in terms of fitness and robustness) were more likely to perform satisfactorily for selection with the inclusion of phantom groups than without it. It was recommended that data in the national Dohne Merino analysis be transformed proportion of contemporary group means to account for heterogeneous contemporary group variances. Phantom parent groups should also be applied to the analysis to increase the probability of those animals entering the breeding flock from a commercial base being selected.
AFRIKAANSE OPSOMMING: Genetiese kovariansies vir liggaamgewig, skoonvaggewig en veseldikte is vir die SA Dohne Merino bevolking in Suid-Afrika beraam nadat data getransformeer as ‘n proporsie van die kontemporêre groep gemiddelddes uitgedruk is. Die data het rekords in van liggaamsgewig, skoonvaggewig en veseldikte van 282 513 diere oor die tydperk van 1992 tot 2011 ingesluit. Die data sluit rekords van 5 698 vaars, 105 886 moers en 6 291 kontemporêre groepe in. 'n Meer-eienskapdieremodel met 'n additiewe diere-effekte sowel as 'n vaar-kudde-seisoen (SFS) interaksie is as ewekansige effekte gemodelleer, bykomstig tot die vaste effekte van kontemporêre groep (FYSSM) (6 291 klasse), geboortestatus (enkelling, tweeling of drieling), ouderdom van moer (1 tot 3 jaar) gepas as 'n lineêre regressive, sowel as ouderdom by prestasie meting as ‘n polinoom gepas. Die beraamde direkte oorerflikheid (SF) van liggaamgewig, skoonvaggewig en veseldikte van die meereienskap dieremodel was onderskeidelik 0,265 (0,005), 0,210 (0,004) en 0,437 (0,005). Die genetiese korrelasies van liggaamsgewig met skoonvaggewig en veseldikte was 0,035 (0.015) en 0,139 (0.011) onderskeidelik, terwyl die genetiese korrelasie tussen skoonvaggewig en veseldikte 0,169 (0.012) beloop het. Liggaamsgewig het onderskeie fenotipiese korrelasies van 0,327 (0.002) en 0.150 (0.002) met skoonvaggewig en veseldikte gehad, terwyl skoonvaggewig ‘n fenotipiese korrelasie van 0.190 (0.002) met veseldikte gehad het. Die medium tot hoë oorerflikheidhede dui daarop dat daar aansienlike genetiese variasie voorkom, wat kan aanleiding gee tot genetiese vordering as seleksie op die eienskappe toegepas word. Genetiese korrelasies was oor die algemeen laag wat daarop dui dat vordering in al die eienskappe deur ‘n wetenskaplike seleksie program moontlik is. Die aanspraak is deur genetiese tendense in die studie bevestig. Die transformasie van data na proporsies van kontemporêre groep gemiddeldes het daartoe gelei dat teelwaardes aangepas word. Die teelwaardes van vaars uit kuddes met ‘n omgewing wat beperk word (Lae groep:180 vaars), is opwaarts aangepas. Daarenteen is vaars uit 'n nie-beperkende produksie omgewing (Hoë groep:146 vaars) se teelwaardes afwaarts aangepas. Hierdie effekte was veral ooglopend vir die kwantitatiewe eienskappe, liggaamgewig en skoonvaggewig, maar tot 'n mindere mate vir veseldikte. Die transformasie het daartoe gelei dat die genetiese tendense for die Lae groep aangepas word om vergelykbaar te wees met die Hoë groep vir liggaamsgewig en skoonvaggewig. Die gevolgtrekking was gemaak dat meer toepaslike vaar teelwaardes, bereken vanaf getransformeerde data, verkry word vir regoor die diverse omgewings wat produksie van plaaslike Dohne Merinos ondersteun. Die genetiese waarde van diere wat die aangetekende populasie uit ‘n kommersiële agtergrond (F4 diere) binnekom was laer as die volledig aangetekende gedeelte van die populasie. Die insluiting van skimgroepe in die genetiese ontleding het tot genetiese tendense gelei wat die F4 diere vergelykbaar gemaak het met diere in die ontleding wat wel stamboekinligting het. Die gevolgtrekking is gemaak dat diere van ‘n kommersiële agtergrond (wat aanvaar word om voordele in te hou in terme van fiksheid en robuustheid) meer geredelik geselekteer sal word vir die stoet met die insluiting van skimgroepe as daarsonder. Dit word aanbeveel dat die data in die Nasionale Dohne Merino na proporsies van die kontemporêre groepgemiddeldes getrensformeer word om vir heterogene kontemporêre groep variansies voorsiening te maak. Skimgroepe moet ook gepas word in die ontleding om die waarskynlikheid te verhoog dat diere vanuit 'n kommersiële basis, ook geselekteer sal word.

Bibliography: leaves 325-341. Skin and fleece measurements were recorded at different ages for both male and female sheep from the Turretfield Merino Resource Flock and used to estimate the heritability of each trait and the phenotypic and genetic correlations among and between the skin and fleece traits. Generally, the heritability of each trait was high, which indicates that both the fleece and skin traits should respond well to selection.

Includes bibliographical references (leaves 325-341).
xxvii, 341 leaves : ill. ; 30 cm.
Skin and fleece measurements were recorded at different ages for both male and female sheep from the Turretfield Merino Resource Flock and used to estimate the heritability of each trait and the phenotypic and genetic correlations among and between the skin and fleece traits. Generally, the heritability of each trait was high, which indicates that both the fleece and skin traits should respond well to selection.
Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Science, 2001

The Elsenburg Merino flock has been divergently selected for the ability of ewes to rear multiple offspring since 1986. Updated genetic trends for reproduction are reported for the Elsenburg Merino resource flock. The objective was to determine whether genetic trends estimated previously for the Elsenburg Merino Resource flock changed significantly with the introduction of genetic material from the industry to the high (H) line. All analyses included the full pedigree file, consisting of 6547 individuals. Heritability estimates were 0.08 ± 0.02 for number of lambs weaned and 0.11 ± 0.02 for corrected weight of lamb weaned. The ewe permanent environment variance was estimated at 0.09 ± 0.02 and 0.11 ± 0.02 for number of lambs weaned and for corrected weight of lamb weaned, respectively. Genetic trends for the H and low (L) lines were divergent (P < 0.05) for all reproduction traits during the period prior to the observed breakpoints. Progress for number of lambs weaned in the H line stabilised after 1999 while a decline in response for weight of lamb weaned in the H line occurred after 2003. The change points may result from reduced selection intensity during the formation of reciprocal crossbred lines, or the introduction of unrelated industry sires in the H line. The pedigree was analysed and inbreeding trends computed for the H and L lines with the aim to test the significance of inbreeding within the lines. The software packages used for the statistical analyses were ENDOG v4.8 and POPREP web analysis software. The average inbreeding coefficients (F) were 1.47% and 0.73% for the divergently selected H and L lines. The rate of inbreeding (ΔF) per generation was 0.5% for the H line and 0.6% in the L line. The overall rates of inbreeding per generation were different in the H and L lines but within acceptable levels. The L line, however, showed an unwanted recent increase in inbreeding that will need to be considered in future. Since 2003, part of the Elsenburg Merino breeding flock was subjected to structured reciprocal within-breed crossing. Lamb survival traits and ewe reproductive performance of purebred (H and L) and reciprocal crosses (HxL and LxH) were evaluated using least squares analyses. Levels of heterosis were also assessed. The mean survival of the two crossbred lines was notably superior to the midparent value in absolute terms, although the contrast did not reach statistical significance (P = 0.098). Further research is required to establish whether this within breed heterosis for lamb survival can be exploited to decrease lamb losses. Reproduction, number of lambs born (NLB) and number of lambs weaned (NLW) in the H line was higher than in the L line (P < 0.05) while the two crossbred lines were intermediate and different from both the H line and the L line (P < 0.05) from the analyses of annual reproduction and overall “lifetime” reproduction across three lambing opportunities. Individual heterosis for annual reproduction was estimated at 2.2% for NLB, 13.8% for NLW and 8.5% for corrected weight of lamb weaned (TWW), with the estimate for NLW reaching significance (P < 0.05). Corresponding estimates for total production over three lambing opportunities were 8.7% for TNLB, 19.1% for TNLW and 13.8% for TTWW, with the estimate for NLW reaching significance (P < 0.05). Ten RAPD markers were used to study molecular divergence between the H and L lines. Phenotypic data on the lifetime reproduction of ewes born in 1999 and 2000 indicated that reproduction in the H line ewes was markedly higher than that of L line contemporaries (P < 0.01). The RAPD assay, conducted on 15 ewes from each line, used eight primers and produced 87% polymorphic loci. The mean coefficient of genetic differentiation between lines (Gst) was estimated to be 0.25. In conclusion, the H and L lines were shown to be divergent for genetic trends and levels of inbreeding. The derived estimates of heterosis may also be used to infer divergence between the lines and significant molecular divergence proven using RAPD assays.
Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

VSR Dukkipati (2007). A search for genetic factors influencing immune responses to Mycobacterium avium subspecies paratuberculosis. Doctoral thesis, Massey University, Palmerston North, New Zealand. A study was conducted to identify associations between genetic markers and immune responses in Australian fine-wool Merino sheep to a killed Mycobacterium avium subspecies paratuberculosis (Map) vaccine (GudairTM). Blood samples and immune response data (antibody and interferon gamma, IFN-gamma results) were obtained from 934 sheep from a longterm Map vaccination trial undertaken on three independent properties in New South Wales, Australia. Blood samples were genotyped for eight microsatellite markers that included four (DYMS1, OLADRW, OLADRB and SMHCC1) from the Ovar-Mhc region, two each from the SLC11A1 (OVINRA1 and OVINRA2) and IFN-gamma (o(IFN)gamma and OarKP6) gene regions. Vaccination with GudairTM induced strong antibody and IFN-gamma responses as early as two weeks post-vaccination. Between-property differences in magnitude and trend of immune responses, concomitant with season of vaccination and magnitude of natural infection prevalent in individual flocks, were evident. Immune responses in controls on all the three properties remained consistently low, except for slightly elevated IFN-gamma levels at a few time points in controls of properties 2 and 3, concomitant with exposure to natural infection. There were only 2 alleles and 3 genotypes for marker o(IFN)gamma but other loci exhibited extensive polymorphisms, the most occurring at OLADRW which had 42 alleles and 137 genotypes. Heterozygosities varied between 33% (OVINRA2) and 87% (SMHCC1), while polymorphic information contents ranged from 0.31 (o(IFN)gamma) to 0.88 (OLADRW). Genotypes at loci DYMS1, OLADRB, SMHCC1, OVINRA1 and o(IFN)gamma were in Hardy- Weinberg equilibrium (HWE), while those at OarKP6 were in HWE only when rare alleles (<1.0% frequency) were pooled with the closest size class. Departure from HWE, resulting from possible preferential amplification of alleles in heterozygotes, was evident at OLADRW and OVINRA2. Associations between immune responses and genetic polymorphisms at the marker loci were examined by analysing both genotypic and allelic affects. The study revealed several genotypes/alleles at different marker loci to be significantly associated with antibody and IFN-gamma responses to vaccination with GudairTM. However, the majority of those effects were inconsistent across the three properties. Based on significance and consistency in effects across the three properties, five genotypes (two at DYMS1 and one each at OLADRB, SMHCC1 and OVINRA1) and three alleles (one each at DYMS1, OLADRB and o(IFN)gamma) were considered either ‘probable’ or ‘most likely’ to be associated with low IFN-gamma responses, while a genotype at o(IFN)gamma was considered ‘most likely’ to influence high IFN-gamma responses. An allele at OarKP6 was considered ‘probable’ to be associated with low antibody responses to vaccination. Considering the significance of IFN-gamma responses in protection against Map, it is likely that the identified genotype/alleles influencing IFN-gamma responses to vaccination would also influence immune responses to natural Map infections. However, further studies need to be conducted to determine the role of these marker genotypes/alleles in protection against paratuberculosis under natural infection conditions. Key words: paratuberculosis, OJD, Johne’s disease, sheep, immune response, genetic markers, gene polymorphisms, MHC, SLC11A1, IFN-gamma