Genetic burden associated with varying degrees of disease severity in endometriosis

Endometriosis is primarily characterized by the presence of tissue resembling endometrium outside the uterine cavity and is usually diagnosed by laparoscopy. The most commonly used classification of disease, the revised American Fertility Society (rAFS) system to grade endometriosis into different stages based on disease severity (I to IV), has been questioned as it does not correlate well with underlying symptoms, posing issues in diagnosis and choice of treatment. Using two independent European genome-wide association (GWA) datasets and top-level classification of the endometriosis cases based on rAFS [minimal or mild (Stage A) and moderate-to-severe (Stage B) disease], we previously showed that Stage B endometriosis has greater contribution of common genetic variation to its aetiology than Stage A disease. Herein, we extend our previous analysis to four endometriosis stages [minimal (Stage I), mild (Stage II), moderate (Stage III) and severe (Stage IV) disease] based on the rAFS classification system and compared the genetic burden across stages. Our results indicate that genetic burden increases from minimal to severe endometriosis. For the minimal disease, genetic factors may contribute to a lesser extent than other disease categories. Mild and moderate endometriosis appeared genetically similar, making it difficult to tease them apart. Consistent with our previous reports, moderate and severe endometriosis showed greater genetic burden than minimal or mild disease. Overall, our results provide new insights into the genetic architecture of endometriosis and further investigation in larger samples may help to understand better the aetiology of varying degrees of endometriosis, enabling improved diagnostic and treatment modalities.

Antifertility effect of tamoxifen as tested in the female bonnet monkey (Macaca radiata)

The administration of a potent antiestrogen, tamoxifen at a dose of 3 mg/kg body weight/day orally post-coitally to cycling mated bonnet monkeys(Macaca radiata) from days 18–30 of cycle resulted in inhibition of establishment of pregnancy in 9 out of 10 monkeys. Tamoxifen effect was not due to interference with luteal function. The effect was specific to tamoxifen as exogenously administered progesterone could not reverse it. In addition to suggesting a role for estrogen in maintenance of early pregnancy in the primate the present study could be a prelude to the development of an effective post-ovulatory approach for regulation of fertility in the human female

No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis

STUDY QUESTION Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk? SUMMARY ANSWER We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS. WHAT IS KNOWN ALREADY The rs61764370 SNP in the 3' untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis. STUDY DESIGN, SIZE AND DURATION This was a case-control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012. PARTICIPANTS/MATERIALS, SETTINGAND METHODS We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform. MAIN RESULTS AND THE ROLE OF CHANCE There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88-1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087-0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk. LIMITATIONS AND REASONS FOR CAUTION The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis. WIDER IMPLICATIONS OF THE FINDINGS The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk. STUDY FUNDING/COMPETING INTEREST(S) The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.

Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases

Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62x10(-)(9)-1.01x10(-)(1)(2)). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9x10(-)(3)). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4x10(-)(8)(8)]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.

High-density fine-mapping of a chromosome 10q26 linkage peak suggests association between endometriosis and variants close to CYP2C19

OBJECTIVE To refine a previously reported linkage peak for endometriosis on chromosome 10q26, and conduct follow-up analyses and a fine-mapping association study across the region to identify new candidate genes for endometriosis. DESIGN Case-control study. SETTING Academic research. PATIENT(S) Cases=3,223 women with surgically confirmed endometriosis; controls=1,190 women without endometriosis and 7,060 population samples. INTERVENTION(S) Analysis of 11,984 single nucleotide polymorphisms on chromosome 10. MAIN OUTCOME MEASURE(S) Allele frequency differences between cases and controls. RESULT(S) Linkage analyses on families grouped by endometriosis symptoms (primarily subfertility) provided increased evidence for linkage (logarithm of odds score=3.62) near a previously reported linkage peak. Three independent association signals were found at 96.59 Mb (rs11592737), 105.63 Mb (rs1253130), and 124.25 Mb (rs2250804). Analyses including only samples from linkage families supported the association at all three regions. However, only rs11592737 in the cytochrome P450 subfamily C (CYP2C19) gene was replicated in an independent sample of 2,079 cases and 7,060 population controls. CONCLUSION(S) The role of the CYP2C19 gene in conferring risk for endometriosis warrants further investigation.

Agroforestry systems for sustainable livelihoods and improved land management in the East Usambara Mountains, Tanzania

Forest destruction for agriculture continues to be a major threat to the rich biological diversity in the East Usambara Mountains in the north-eastern corner of Tanzania. The highest ratio of endemic plant and animal species found on 100 km2 anywhere in the world is depending on the remaining natural forests. Forests are vitally important for the local population in many different ways, and nationally they are an important source of water and hydroelectricity. The soils, of low fertility and mostly acidic Ferrasols, mainly have the nutrients in the topsoil. After clear-cutting, the soils soon become poor when the topsoil is eroded. High-value cardamom is nowadays unsustainably cultivated in the natural forests of the East Usambaras. The general aim was to study the possibilities to develop new profitable and sustainable agroforestry systems for the benefit of the local people that could contribute to relieving the pressure on the remaining natural forests in the East Usambara Mountains. Results from a spice crop agroforestry trial, established in cooperation with a local farmer, showed a clear advantage of intercropping cardamom (Elettaria cardamomum) and black pepper (Piper nigrum) with trees, especially with Grevillea robusta. The nitrogen fixing tree species Gliricidia sepium also improved the nitrogen and organic matter content of the soil over levels found in the natural forest. With improved agroforestry methods for spice production the households generated as much as13 times the net income obtained with traditional forest cultivation practices. There are thus sustainable and profitable ways to cultivate spices as cash crops in well-managed homegardens. However, the farmers need stable markets, access to credit and comprehensive extension services. The soil fertility depletion should be reversed with organic manure application and an enabling policy environment for the smallholder-farming sector. Strong farmers organisations and equal rights to resources and decision-making are needed. Organic spices have an increasing demand, and their export would be profitable for these farmers. What is, however, most needed for a change is a political will of a government that understands the importance of agricultural and forestry development for poverty reduction.

The role of tillage, fertiliser and forage species in sustaining dairying based on crops in southern Queensland 2. Double-crop and summer sole-crop systems.

Dairy farms located in the subtropical cereal belt of Australia rely on winter and summer cereal crops, rather than pastures, for their forage base. Crops are mostly established in tilled seedbeds and the system is vulnerable to fertility decline and water erosion, particularly over summer fallows. Field studies were conducted over 5 years on contrasting soil types, a Vertosol and Sodosol, in the 650-mm annual-rainfall zone to evaluate the benefits of a modified cropping program on forage productivity and the soil-resource base. Growing forage sorghum as a double-crop with oats increased total mean annual production over that of winter sole-crop systems by 40% and 100% on the Vertosol and Sodosol sites respectively. However, mean annual winter crop yield was halved and overall forage quality was lower. Ninety per cent of the variation in winter crop yield was attributable to fallow and in-crop rainfall. Replacing forage sorghum with the annual legume lablab reduced fertiliser nitrogen (N) requirements and increased forage N concentration, but reduced overall annual yield. Compared with sole-cropped oats, double-cropping reduced the risk of erosion by extending the duration of soil water deficits and increasing the time ground was under plant cover. When grown as a sole-crop, well fertilised forage sorghum achieved a mean annual cumulative yield of 9.64 and 6.05 t DM/ha on the Vertosol and Sodosol, respectively, being about twice that of sole-cropped oats. Forage sorghum established using zero-tillage practices and fertilised at 175 kg N/ha. crop achieved a significantly higher yield and forage N concentration than did the industry-standard forage sorghum (conventional tillage and 55 kg N/ha. crop) on the Vertosol but not on the Sodosol. On the Vertosol, mean annual yield increased from 5.65 to 9.64 t DM/ha (33 kg DM/kg N fertiliser applied above the base rate); the difference in the response between the two sites was attributed to soil type and fertiliser history. Changing both tillage practices and N-fertiliser rate had no affect on fallow water-storage efficiency but did improve fallow ground cover. When forage sorghum, grown as a sole crop, was replaced with lablab in 3 of the 5 years, overall forage N concentration increased significantly, and on the Vertosol, yield and soil nitrate-N reserves also increased significantly relative to industry-standard sorghum. All forage systems maintained or increased the concentration of soil nitrate-N (0-1.2-m soil layer) over the course of the study. Relative to sole-crop oats, alternative forage systems were generally beneficial to the concentration of surface-soil (0-0.1 m) organic carbon and systems that included sorghum showed most promise for increasing soil organic carbon concentration. We conclude that an emphasis on double-or summer sole-cropping rather than winter sole-cropping will advantage both farm productivity and the soil-resource base.

Swan’s Lagoon Celebrating 50 years

Swan’s Lagoon, which is 125 km south-south-west of Townsville, was purchased by the Queensland Government as a beef cattle research station in 1961. It is situated within the seasonally-dry tropical spear grass region of North Queensland. The station was expanded from 80 km2 to 340 km2 by purchase of the adjoining Expedition block in 1978. The first advisory committee formed and initiated research in 1961. The median annual rainfall of 708 mm (28 inches) is highly variable, with over 80% usually falling in December–April. Annual evaporation is 2.03 metres. The 60% of useable area is mostly flat with low fertility duplex soils, of which more than 50% is phosphorus deficient. Natural spear grass-based pastures predominate over the station. Swan’s Lagoon research has contributed to understanding the biology of many aspects of beef production for northern Australia. Research outcomes have provided options to deal with the region’s primary challenges of weaning rates averaging less than 60%, annual growth rates averaging as little as 100 kg, high mortality rates and high management costs. All these relate to the region’s variable and highly seasonal rainfall—challenges that add to insect-borne viruses, ticks, buffalo fly and internal parasites. As well as the vast amount of practical beef production science produced at Swan’s Lagoon, generations of staff have been trained there to support beef producers throughout Queensland and northern Australia to increase their business efficiency. The Queensland Government has provided most of the funds for staffing and operations. Strong beef industry support is reflected in project funding from meat industry levies, managed by Meat and Livestock Australia (MLA) and its predecessors. MLA has consistently provided the majority of operational research funding since the first grant for ‘Studies of management practices, adaption of different breeds and strains to tropical environments, and studies on tick survival and resistance’ in 1962–63. A large number of other agencies and commercial companies have also supported research.

Cat's claw creeper vine, Macfadyena unguis-cati (Bignoniaceae), invasion impacts: comparative leaf nutrient content and effects on soil physicochemical properties

Macfadyena unguis-cati (L.) Gentry (Bignoniaceae) is a major environmental weed in coastal Queensland, Australia. There is a lack of quantitative data on its leaf chemistry and its impact on soil properties. Soils from infested vs uninfested areas, and leaves of M. unguis-cati and three co-occurring vine species (one exotic, two native) were collected at six sites (riparian and non-riparian) in south-eastern Queensland. Effects of invasion status, species, site and habitat type were examined using univariate and multivariate analyses. Habitat type had a greater effect on soil nutrients than on leaf chemistry. Invasion effect of M. unguis-cati on soil chemistry was more pronounced in non-riparian than in riparian habitat. Significantly higher values were obtained in M. unguis-cati infested (vs. uninfested) soils for ~50% of traits. Leaf ion concentrations differed significantly between exotic and native vines. Observed higher leaf-nutrient load (especially nitrogen, phosphorus and potassium) in exotic plants aligns with the preference of invasive plant species for disturbed habitats with higher nutrient input. Higher load of trace elements (aluminium, boron, cadmium and iron) in its leaves suggests that cycling of heavy-metal ions, many of which are potentially toxic at excess level, could be accelerated in soils of M. unguis-cati-invaded landscape. Although inferences from the present study are based on correlative data, the consistency of the patterns across many sites suggests that M. unguis-cati may improve soil fertility and influence nutrient cycling, perhaps through legacy effects of its own litter input.

Soil hydrological properties and conditions, site preparation, and the long-term performance of planted Scots pine (Pinus sylvestris L.) on upland forest sites in Finnish Lapland

Scots pine (Pinus sylvestris L.) and Norway spruce (Picea abies (L.) Karst.) forests dominate in Finnish Lapland. The need to study the effect of both soil factors and site preparation on the performance of planted Scots pine has increased due to the problems encountered in reforestation, especially on mesic and moist, formerly spruce-dominated sites. The present thesis examines soil hydrological properties and conditions, and effect of site preparation on them on 10 pine- and 10 spruce-dominated upland forest sites. Finally, the effects of both the site preparation and reforestation methods, and soil hydrology on the long-term performance of planted Scots pine are summarized. The results showed that pine and spruce sites differ significantly in their soil physical properties. Under field capacity or wetter soil moisture conditions, planted pines presumably suffer from excessive soil water and poor soil aeration on most of the originally spruce sites, but not on the pine sites. The results also suggested that site preparation affects the soil-water regime and thus prerequisites for forest growth over two decades after site preparation. High variation in the survival and mean height of planted pine was found. The study suggested that on spruce sites, pine survival is the lowest on sites that dry out slowly after rainfall events, and that height growth is the fastest on soils that reach favourable aeration conditions for root growth soon after saturation, and/or where the average air-filled porosity near field capacity is large enough for good root growth. Survival, but not mean height can be enhanced by employing intensive site preparation methods on spruce sites. On coarser-textured pine sites, site preparation methods don t affect survival, but methods affecting soil fertility, such as prescribed burning and ploughing, seem to enhance the height growth of planted Scots pines over several decades. The use of soil water content in situ as the sole criterion for sites suitable for pine reforestation was tested and found to be a relatively uncertain parameter. The thesis identified new potential soil variables, which should be tested using other data in the future.

Male traits and herd reproductive capability in tropical beef cattle. 1. Experimental design and animal measures

Research into the genetics of whole herd profitability has been a focus of the Beef Cooperative Research Centre for Beef Genetic Technologies over the past decade and it has been identified that measures of male reproduction may offer a potential indirect means of selecting for improved female reproduction. This paper describes the experimental design and provides a descriptive analysis of an array of male traits in Brahman and Tropical Composite genotypes managed under the medium to high stress, semi-extensive to extensive production systems of northern Australia. A total of 1639 Brahman and 2424 Tropical Composite bulls with known pedigrees, bred and raised in northern Australia, were evaluated for a comprehensive range of productive and reproductive traits. These included blood hormonal traits (luteinising hormone, inhibin and insulin-like growth factor-I); growth and carcass traits (liveweight, body condition score, ultrasound scanned 12-13th rib fat, rump P8 fat, eye muscle area and hip height); adaptation traits (flight time and rectal temperature); and a bull breeding soundness evaluation (leg and hoof conformation, sheath score, length of everted prepuce, penile anatomy, scrotal circumference, semen mass activity, sperm motility and sperm morphology). Large phenotypic variation was evident for most traits, with complete overlap between genotypes, indicating that there is likely to be a significant opportunity to improve bull fertility traits through management and bull selection.

Sperm chromatin in beef bulls in tropical environments

Sperm chromatin status was assessed in 565 Zebu and Zebu crossbred beef bulls in extensive tropical environments using the sperm chromatin structure assay (SCSA). The SCSA involved exposure of sperm to acid hydrolysis for 0.5 or 5.0 minutes, followed by flow cytometry to ascertain relative amounts of double-stranded (normal) and single-stranded (denatured) DNA, which was used to generate a DNA fragmentation index (%DFI). With conventional SCSA (0.5-minute SCSA), 513 bulls (91%) had <15 %DFI, 24 bulls (4%) had 15 to 27 %DFI, and 28 bulls (5%) had >27 %DFI. In 5.0-minute SCSA, 432 bulls (76%) had <15 %DFI, 68 bulls (12%) had 15 to 27 %DFI and 65 bulls (12%) had >27 %DFI. For most bulls, the SCSA was repeatable on two to four occasions; however, because most bulls had <15 %DFI, repeatability of the SCSA will need to be determined in a larger number of bulls in the 15 to 27 %DFI and >27 %DFI categories. The %DFI was negatively correlated with several bull semen parameters and the strongest negative correlation was with normal sperm. There was a strong positive correlation between %DFI and sperm head abnormalities. Based on these findings, most Zebu beef bulls in extensive tropical environments had relatively stable sperm chromatin. Based on the apparent negative correlations with conventional semen parameters, we inferred that the SCSA measured a unique feature of sperm quality, which has also been suggested for other species. Further studies on the relationships between sperm chromatin stability and fertility are required in beef bulls before chromatin status can be used as an additional predictor of the siring capacity of individual bulls in extensive multiple-sire herds. (C) 2013 Elsevier Inc. All rights reserved.

Pathogenicity of Blumeria graminis f. sp. hordei in Australia in 2010 and 2011

A survey of the Australian barley powdery mildew (Blumeria graminis f. sp. hordei) population was conducted in 2010 and 2011. Three hundred and sixty-two isolates of the pathogen were collected from 18 locations across all six states of Australia. Thirty-two barley differentials were used and 11 genotypes were able to differentiate the population with virulence frequencies varying from 14.5 % to 96.6 %. Twenty-seven pathotypes were detected. Fifteen of them were found in both years and they represented 92.0 % of all isolates examined. No virulence was found on a further 16 major genes for resistance (Mla1, Mla3, Mla6, Mla7, Mla9, Mla10, Mla12, Mla13, Mla23, MlaN81, Mlh, MlLa, Mlp1, Ml(IM9), Ml(St) and mlo) indicating a relatively simple population and the ready availability of diverse sources of resistance. This paper reports the powdery mildew virulences present in Australia, provides intelligence for future resistance breeding and sets a basis for further virulence studies.

Quantitative trait loci detection and benefits from marker-assisted selection in dairy cattle

Knowing the chromosomal areas or actual genes affecting the traits under selection would add more information to be used in the selection decisions which would potentially lead to higher genetic response. The first objective of this study was to map quantitative trait loci (QTL) affecting economically important traits in the Finnish Ayrshire population. The second objective was to investigate the effects of using QTL information in marker-assisted selection (MAS) on the genetic response and the linkage disequilibrium between the different parts of the genome. Whole genome scans were carried out on a grand-daughter design with 12 half-sib families and a total of 493 sons. Twelve different traits were studied: milk yield, protein yield, protein content, fat yield, fat content, somatic cell score (SCS), mastitis treatments, other veterinary treatments, days open, fertility treatments, non-return rate, and calf mortality. The average spacing of the typed markers was 20 cM with 2 to 14 markers per chromosome. Associations between markers and traits were analyzed with multiple marker regression. Significance was determined by permutation and genome-wise P-values obtained by Bonferroni correction. The benefits from MAS were investigated by simulation: a conventional progeny testing scheme was compared to a scheme where QTL information was used within families to select among full-sibs in the male path. Two QTL on different chromosomes were modelled. The effects of different starting frequencies of the favourable alleles and different size of the QTL effects were evaluated. A large number of QTL, 48 in total, were detected at 5% or higher chromosome-wise significance. QTL for milk production were found on 8 chromosomes, for SCS on 6, for mastitis treatments on 1, for other veterinary treatments on 5, for days open on 7, for fertility treatments on 7, for calf mortality on 6, and for non-return rate on 2 chromosomes. In the simulation study the total genetic response was faster with MAS than with conventional selection and the advantage of MAS persisted over the studied generations. The rate of response and the difference between the selection schemes reflected clearly the changes in allele frequencies of the favourable QTL. The disequilibrium between the polygenes and QTL was always negative and it was larger with larger QTL size. The disequilibrium between the two QTL was larger with QTL of large effect and it was somewhat larger with MAS for scenarios with starting frequencies below 0.5 for QTL of moderate size and below 0.3 for large QTL. In conclusion, several QTL affecting economically important traits of dairy cattle were detected. Further studies are needed to verify these QTL, check their presence in the present breeding population, look for pleiotropy and fine map the most interesting QTL regions. The results of the simulation studies show that using MAS together with embryo transfer to pre-select young bulls within families is a useful approach to increase the genetic merit of the AI-bulls compared to conventional selection.

Classifying genotype by environment interactions for targeted germplasm deployment with a focus on Eucalyptus

A novel methodology for describing genotype by environment interactions estimated from multi-environment field trials is described and an empirical example using an extensive trial network of eucalypts is presented. The network of experiments containing 65 eucalypts was established in 38 replicated field trials across the tropics and subtropics of eastern Australia, with a selection of well-tested species used to provide a more detailed examination of productivity differentials across environmental gradients. By focusing on changes in species’ productivity across environmental gradients, the results are applicable for all species established across the range of environments evaluated in the trial network and simultaneously classify species and environments so that results may be applied across the landscape. The methodology developed was able to explain most (93 %) of the variation in the selected species relative changes in productivity across the various environmental variables examined. Responses were primarily regulated by changes in variables related to water availability and secondarily by temperature related variables. Clustering and ordination can identify groups of species with similar physiological responses to environment and may also guide the parameterisation and calibration of process based models of plant growth. Ordination was particularly useful in the identification of species with distinct environmental response patterns that would be useful as probes for extracting more information from future trials.