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William G. Hill, universally known as Bill Hill, died on December 17, 2021, aged 81. Bill also compared the observed and predicted long-term response to selection and concluded that these data had little power to distinguish among different models for quantitative genetic variation, including the "infinitesimal model" that postulates a very large number of loci with very small effects (Hill 2010). Appropriately, John Sved and Bill wrote an insightful I Perspective i in Genetics reviewing 100 years of work on LD (Sved and Hill 2018). In particular, he was the first to quantify the role of new mutations in producing the variability needed for long-term continued responses to selection, which are such a remarkable feature of many artificial selection experiments and animal and plant breeding programs (Hill 1982a,b; Keightley and Hill 1983). [Extracted from the article]

The genetics and evolution of complex traits, including quantitative traits and disease, have been hotly debated ever since Darwin. A century ago, a paper from R.A. Fisher reconciled Mendelian and biometrical genetics in a landmark contribution that is now accepted as the main foundation stone of the field of quantitative genetics. Here, we give our perspective on Fisher's 1918 paper in the context of how and why it is relevant in today's genome era. We mostly focus on human trait variation, in part because Fisher did so too, but the conclusions are general and extend to other natural populations, and to populations undergoing artificial selection. [ABSTRACT FROM AUTHOR]

Juan Obarrio made his first research trip to the country in 2000, when the Mozambican state reversed the ban on the customary, a juridico-political reform recognizing so-called traditional authorities and incorporating them into contemporary local governance and development projects. Insofar as it is an anthropology of the state, his study eschews dichotomous views of the state and society, arguing a Foucauldian position that the state is a relation rather than a structural apparatus. At the same time state agents and development-aid donors see custom and customary authorities - through which traditional spirituality is manifested - as key components of a distinctly local form of democratization and decentralization. [Extracted from the article]

Background: Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs. Results: In total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %). Conclusions: This study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs. [ABSTRACT FROM AUTHOR]

This article examines the emergent field of media archaeology as offering a materialist approach to new media and specifically the Internet, constituting a ‘travelling discipline’ or ‘indiscipline’ rather than a new disciplinary paradigm. Following the lead of Siegfried Zielinski, it provides less an archaeology than an ‘anarchaeology’ of media archaeology, understanding this term in political as well as methodological terms. To do so, it charts a trajectory through some of the sources of media archaeology and its key theoretical articulations in the work of Zielinski and Friedrich Kittler up to its more recent articulations in the work of Jussi Parikka and Wolfgang Ernst. It uses this theoretical trajectory to illuminate some of the key problematics of media archaeology, in terms of both its practical application as a form of ‘theoretical circuit breaking’ and its most imaginative speculations as not only a material but even a geological approach to media as evident in Parikka’s most recent work, by way of such phenomena as the ‘vernacular Web’ and the problematics of e-waste. Throughout, it pays close attention to the value of media archaeology as a set of methods for new media research in relation to more established methodologies in media studies ranging from medium histories to cultural studies. In particular, it argues for articulating media archaeological approaches with media ecological ones, in order to bring out more clearly both the political stakes of the field and its potential contribution to studies of digital media. [ABSTRACT FROM AUTHOR]

Heritability is a population parameter of importance in evolution, plant and animal breeding, and human medical genetics. It can be estimated using pedigree designs and, more recently, using relationships estimated from markers. We derive the sampling variance of the estimate of heritability for a wide range of experimental designs, assuming that estimation is by maximum likelihood and that the resemblance between relatives is solely due to additive genetic variation. We show that well-known results for balanced designs are special cases of a more general unified framework. For pedigree designs, the sampling variance is inversely proportional to the variance of relationship in the pedigree and it is proportional to 1/N, whereas for population samples it is approximately proportional to 1/N², where N is the sample size. Variation in relatedness is a key parameter in the quantification of the sampling variance of heritability. Consequently, the sampling variance is high for populations with large recent effective population size (e.g., humans) because this causes low variation in relationship. However, even using human population samples, low sampling variance is possible with high N. [ABSTRACT FROM AUTHOR]

This article is driven by the equivocal possibility of doing analytic justice to the cosmo-ontology of the Motu-Koita, of Papua New Guinea, as it was when early missionaries and colonial officers credited south-east-coastal indigenes only with unsystematized beliefs and superstitions about invisible forces. It focuses on an incident in which traditional 'sorcerers' were put to the test by the early colonial administration, which was trying to destroy local beliefs in sorcery. By interrogating the discursive stereotypes brought to this episode by the administration, and problematizing the translation and understanding of some Motu-Koita terminology, it attempts some first steps toward a more nuanced understanding of the pre- European-contact lifeworld of the Motu-Koita. [ABSTRACT FROM AUTHOR]

Courts of law in Melanesian countries, particularly in the aftermath of the colonial period, have attempted to accommodate 'custom'. In Papua New Guinea they commonly hear land claims under terms of reference that acknowledge the wide variety of customs among the many ethno-linguistic groups comprising the nation. A corollary of this liberalism is that, in theory, they admit 'traditional evidence' including legends and myths. Yet as courts of law they are required to apply some criteria of proof and to search for the 'truth' by examining the 'facts'. A long-running land case from Papua New Guinea and its aftermath raises interesting questions about what happens when oral history encounters these legal imperatives, and may help us appreciate why Melanesians often do not regard a court's decision as final. [ABSTRACT FROM AUTHOR]

This essay examines Franco Berardi's use of cinema as a minor, yet significant, aspect of his work. His most recent work has suggested a profound mutation of human subjectivity under the pressure of the imposition of a range of technical automatisms of which the digital is the latest and the one which has the most profound effects. What is less frequently remarked on in Bifo's work is that the diagnosis of these mutations of subjectivity are frequently carried out in relation to the artistic cartographies generated by both film and media art, with a tendency to favour the former. For example, there are frequent references in his work to Bergman's The Serpent's Egg (1977) and Gus van Sant's Elephant (2003), to give only two examples. This article will focus specifically on his use of cinematic cartographies, by which I mean the ways cinematic works provide spatio-temporal mappings of particular political, subjective and affective conditions. [ABSTRACT FROM AUTHOR]

In the 1970s the Motu-Koita, traditional inhabitants of what is now the National Capital District of Papua New Guinea, inaugurated a yearly cultural festival thematically based on traditional coastal trading voyages known as hiri. Contestation over the location and commercialization of the festival in the capital city developed in the new century as one distant village claimed to 'own' the hiri. The Motu-Koita view of their past and their identity has been affected by their encounter with Christianity, colonialism and its aftermath, and the rhetoric of the villagers' claims drew on criteria of authenticity, cultural purity, and exclusiveness which are arguably contemporary rather than 'traditional'. This article reviews Motu-Koita history, the story of the origin of the hiri, and the local politics of the cultural festival. It attempts to understand the way the past, which was formerly mythopoeically invoked, is being historicized and thereby fixed in new local discourses of cultural and heritage rights and ownership, as Melanesians come to terms with the effects of global processes on their traditions and other resources. [ABSTRACT FROM AUTHOR]

Most traits of economic importance in livestock are either quantitative or complex. Despite considerable efforts, there has been only limited success in identifying the polymorphisms that cause variation in these traits. Nevertheless, selection based on estimated breeding values (BVs), calculated from data on phenotypic performance and pedigree has been very successful. Genomic tools, such as single nucleotide polymorphism (SNP) chips, have led to a new method of selection called ‘genomic selection’ in which dense SNP genotypes covering the genome are used to predict the BV. In this review we consider the statistical methodology for estimating BVs from SNP data, factors affecting the accuracy, the long-term response to genomic selection and the design of breeding programmes including the management of inbreeding. [ABSTRACT FROM AUTHOR]

Understanding causal relationships between genotypes and phenotypes is a long-standing aim in genetics. In addition to high-throughput technologies that allow the measurement of many DNA variants it is possible to measure gene expression in specific tissues using array technology. "Systems genetics" is an emerging discipline that combines dense data on genotypes, gene expression, and outcome phenotypes to answer fundamental questions about causal pathways from genotype to phenotype. A recent paper by Chen et al. [Mol. Syst. Biol. 5, 310 2009] addressed the question of whether relative levels of mRNA expression help to elucidate causal paths from genotype to phenotype, using drug resistance in yeast as a model. The authors show that data on genetic markers and on gene expression, measured in a drug-free environment, can be combined to predict the growth of a yeast strain in the presence of a drug. They argue that their prediction can be used to identify causal pathways and for a subset of the genes used in prediction, the authors demonstrate that these genes cause an effect on drug sensitivity by deleting the gene or overexpressing it or swapping alleles between strains of yeast. This approach can also be applied to other species, including humans, and may become a tool in the study of personalized medicine. [ABSTRACT FROM AUTHOR]

Genome-wide panels of SNPs have recently been used in domestic animal species to map and identify genes for many traits and to select genetically desirable livestock. This has led to the discovery of the causal genes and mutations for several single-gene traits but not for complex traits. However, the genetic merit of animals can still be estimated by genomic selection, which uses genome-wide SNP panels as markers and statistical methods that capture the effects of large numbers of SNPs simultaneously. This approach is expected to double the rate of genetic improvement per year in many livestock systems. [ABSTRACT FROM AUTHOR]

Most common diseases are caused by multiple genetic and environmental factors. In the last 2 years, genome-wide association studies (GWAS) have identified polymorphisms that are associated with risk to common disease, but the effect of any one risk allele is typically small. By combining information from many risk variants, will it be possible to predict accurately each individual person''s genetic risk for a disease? In this review we consider the lessons from GWAS and the implications for genetic risk prediction to common disease. We conclude that with larger GWAS sample sizes or by combining studies, accurate prediction of genetic risk will be possible, even if the causal mutations or the mechanisms by which they affect susceptibility are unknown. [Copyright &y& Elsevier]

The relative proportion of additive and non-additive variation for complex traits is important in evolutionary biology, medicine, and agriculture. We address a long-standing controversy and paradox about the contribution of non-additive genetic variation, namely that knowledge about biological pathways and gene networks imply that epistasis is important. Yet empirical data across a range of traits and species imply that most genetic variance is additive. We evaluate the evidence from empirical studies of genetic variance components and find that additive variance typically accounts for over half, and often close to 100%, of the total genetic variance. We present new theoretical results, based upon the distribution of allele frequencies under neutral and other population genetic models, that show why this is the case even if there are nonadditive effects at the level of gene action. We conclude that interactions at the level of genes are not likely to generate much interaction at the level of variance. [ABSTRACT FROM AUTHOR]

Ventilator-induced lung injury plays a crucial role in the outcome of patients with acute lung injury. Previous studies have shown a role for the cytokine tumor necrosis factor-α (TNF) in stretch-induced alveolar neutrophil recruitment, but the involvement of TNF in stretch-induced pulmonary edema is unclear. We investigated the effects of TNF through its individual p55 and p75 receptors on early pulmonary edema formation during high stretch ventilation, before neutrophil infiltration. Anesthetized wild-type or TNF receptor single/double knockout mice were ventilated with high tidal volume (~38 ml/kg) for 2 h or until they developed arterial hypotension. Pulmonary edema was assessed by physiological parameters including respiratory mechanics and blood gases, and by lavage fluid protein, lung wet:dry weight ratio, and lung permeability measurements using fluorescence-labeled albumin. High stretch ventilation in wild-type and TNF receptor double knockout animals induced similar pulmonary edema, and only 25-30% of mice completed the protocol. In contrast, the p55 receptor knockout mice were strongly protected from edema formation, with all animals completing the protocol. Myeloperoxidase assay indicated that this protective effect was not associated with decreased pulmonary neutrophil sequestration. The p75 receptor knockout mice, however, displayed increased susceptibility to edema formation, and no animals survived the full 2 h. These results demonstrate a novel role for TNF signaling (independent from its effects on neutrophil recruitment) specifically through the p55 receptor, in promoting high stretch-induced pulmonary edema, whereas p75 signaling may play an opposing role. [ABSTRACT FROM AUTHOR]

This essay will present the film Tout un hiver sans feu/A Long Winter without Fire, directed by Greg Zglinski, as an exemplary case of the contemporary cinematic crossing of Eastern and Western Europe. Using the concept of transvergence developed by Marcos Novak, it will suggest that this film expresses a new experience of East-West mobility that follows the logic of superposition rather than of exile or diaspora. Of particular interest in the film is the use of intercultural communication as a figure of this new mobility as well as the contrast it makes between this transvergent openness to otherness and the dangers of cultural and subjective isolation. The essay will conclude with an examination of fire as a key element of the film which itself functions as a figure of transvergence. [ABSTRACT FROM AUTHOR]

The article focuses on the works of the Slovenian rock group Laibach, the musical component of the multidisciplinary art collective Neue Slowenische Kunst. The author argues that Laibach employed the contradictory context of former Yugoslavia and the emergent Slovenian State in order to interrogate totalitarianisms such as state socialism and fascism as well as the totalitarian dimensions of late capitalism and its global popular culture.

Goddard poses the question of the transversal relations between Guattari's work and feminism by means of a presentation and analysis of Guattari's engagement with "The Pragmatists," a key work by the Polish modernist playwright Stanislaw Witkiewicz. Witkiewicz's prolific work was intimately concerned with problems of sexual difference in relation to modernity. Guattari interprets his aesthetics in general and "The Pragmatists" in particular as constituting what he calls an abstract machine composed of intensive repetitions. Goddard argues that Guattari's engagement with this play provides key insights into the potential relations between his thought and feminism in a more productive manner than some of his more explicit engagements with feminist politics. Instead of seeing either the play or Guattari's interpretation of it as itself feminist, Goddard concludes by suggesting that they provide an artistic artography that is extremely productive for the emergence of a machinic or molecular feminism.

This paper addresses a recent and popular rhetoric in academic literature that women are discriminated against, often in the name of 'custom', in the male-dominated village courts of Papua New Guinea. The rhetoric is interrogated with reference to academic research findings and reports since the early days of the legislatively introduced village court system, and to data from the author's own research in recent years. On the basis of these two sources, it is argued that the evidence does not support the rhetoric, and further that the latter does less than justice to grassroots women in Papua New Guinea by portraying them as relatively passive victims of village courts. On the contrary, fieldwork research findings indicate that women are confident and reasonably successful disputants and that village courts are a community-level resource which is becoming increasingly useful for grassroots women with limited avenues for seeking justice and recompense. [ABSTRACT FROM AUTHOR]

The Motu and the Hula, two south coast Papua New Guinea societies, are linguistically related, have similar social organisation and were economically linked before European colonisation. They were both introduced to Christianity by the London Missionary Society in the late 19th century, and each appeared to incorporate the new religion into their social life and thought quickly and unproblematically. More than a century later, however, generalities about the similar adoption of Christianity by the Mom and the Hula are no longer possible. Nor are generalities about the engagement with Christianity within one or the other group, as individual Motu and Hula villages have unique histories. In this regard, while Christianity has now arguably become part of putative tradition among the Motu, some Hula are experiencing conflict between Christianity and their sense of tradition. In particular, while in the Motu village of Pari Christian virtues are appealed to as part of Pari's conception of itself as a 'traditional' Motu village, the situation in the Hula village of Irupara is more or less the contrary. Many people in Irupara are now lamenting 'tradition' as something lost, a forgotten essence destroyed or replaced by Christianity. Based on fieldwork in both villages, this paper discusses some differences in their engagement with Christianity and compares contemporary perceptions of religion, tradition and identity in both societies, informing a commentary on notions of tradition and anthropological representations of the Melanesian experience of Christianity. [ABSTRACT FROM AUTHOR]

Examines the appropriation of a village court into community sociality and individual aspirations for status in an urban settlement in Port Moresby, Papua New Guinea. Background on the village court system and its practical operation; Discussion on the urban context of the Erima village court; Role of village court magistrate Andrew Kaduello.

Examines single cell contractile mechanics of skeletal muscle before and after 12 weeks of progressive resistance training in older women to compare results with completed single cell progressive resistance training in older men. Gender comparison on cellular muscle adaptations; Sarcopenia-related risks due to muscle strength loss for the aged.

Argues that the structure of the traditional inhabitants Motu-Koitabu society called iduhu in Port Moresby, Papua New Guinea was threatened by missionisation and colonialism. Reexamination of the nature of iduhu; Interpretations in the notions of leadership; Account of disputes that prove on iduhu resiliency.

This article argues for the maintenance of the traditional anthropological analytic distinction between gifts and commodities, against a recent trend to refer to all objects as commodities when exchange is their socially relevant feature. It examines Marx's notions of alienation and commodity fetishism in the context of human praxis and suggests that rigorous, rather than impressionistic, use of these analytic concepts in anthropology can clarify a distinction between gifts and commodities in relation to praxis and intention, rather than exchange. [ABSTRACT FROM AUTHOR]

Most genetic variants associated with fertility in mammals fall in non-coding regions of the genome and it is unclear how these variants affect fertility. Here we use genome-wide association summary statistics for Heifer puberty (pubertal or not at 600 days) from 27,707 Bos indicus, Bos taurus and crossbred cattle; multi-trait GWAS signals from 2119 indicine cattle for four fertility traits, including days to calving, age at first calving, pregnancy status, and foetus age in weeks (assessed by rectal palpation of the foetus); and expression quantitative trait locus for whole blood from 489 indicine cattle, to identify 87 putatively functional genes affecting cattle fertility. Our analysis reveals a significant overlap between the set of cattle and previously reported human fertility-related genes, impling the existence of a shared pool of genes that regulate fertility in mammals. These findings are crucial for developing approaches to improve fertility in cattle and potentially other mammals. The authors identify the genetic variants and genes associated with four fertility-related traits in a well-phenotyped cattle population. [ABSTRACT FROM AUTHOR]

Discusses the use of logistic regression to map quantitative trait loci (QTL) effects in livestock species. Estimates of QTL allele effects, normal error and truncation selection; Use of selective genotyping to detect and locate QTL; Absence of recombination between the genotyped locus and the locus affecting the quantitative trait.

Discusses the Village Court system in Papua New Guinea whose mission included the favoring of custom in the dispensation of justice. Binary notion on the relationship between law and custom; Case from a Port Moresby village court involving an accusation of attempted sorcery; Issues in the case.

Allele specific expression (ASE) is widespread in many species including cows. Therefore, regulatory regions which control gene expression should show cis-regulatory variation which mirrors this differential expression within the animal. ChIP-seq peaks for histone modifications and transcription factors measure activity at functional regions and the height of some peaks have been shown to correlate across tissues with the expression of particular genes, suggesting these peaks are putative regulatory regions. In this study we identified ASE in the bovine genome in multiple tissues and investigated whether ChIP-seq peaks for four histone modifications and the transcription factor CTCF show allele specific binding (ASB) differences in the same tissues. We then investigate whether peak height and gene expression, which correlates across tissues, also correlates within the animal by investigating whether the direction of ASB in putative regulatory regions, mirrors that of the ASE in the genes they are putatively regulating. We found that ASE and ASB were widespread in the bovine genome but vary in extent between tissues. However, even when the height of a peak was positively correlated across tissues with expression of an exon, ASE of the exon and ASB of the peak were in the same direction only half the time. A likely explanation for this finding is that the correlations between peak height and exon expression do not indicate that the height of the peak causes the extent of exon expression, at least in some cases. [ABSTRACT FROM AUTHOR]

Allele specific expression (ASE) is widespread in many species including cows. Therefore, regulatory regions which control gene expression should show cis-regulatory variation which mirrors this differential expression within the animal. ChIP-seq peaks for histone modifications and transcription factors measure activity at functional regions and the height of some peaks have been shown to correlate across tissues with the expression of particular genes, suggesting these peaks are putative regulatory regions. In this study we identified ASE in the bovine genome in multiple tissues and investigated whether ChIP-seq peaks for four histone modifications and the transcription factor CTCF show allele specific binding (ASB) differences in the same tissues. We then investigate whether peak height and gene expression, which correlates across tissues, also correlates within the animal by investigating whether the direction of ASB in putative regulatory regions, mirrors that of the ASE in the genes they are putatively regulating. We found that ASE and ASB were widespread in the bovine genome but vary in extent between tissues. However, even when the height of a peak was positively correlated across tissues with expression of an exon, ASE of the exon and ASB of the peak were in the same direction only half the time. A likely explanation for this finding is that the correlations between peak height and exon expression do not indicate that the height of the peak causes the extent of exon expression, at least in some cases. [ABSTRACT FROM AUTHOR]

Context: Feed is the largest expense on a dairy farm, therefore improving feed efficiency is important. Recording dry-matter intake (DMI) is a prerequisite for calculating feed efficiency. Genetic variation of feed intake and feed efficiency varies across lactation stages and parities. DMI is an expensive and difficult-to-measure trait. This raises the question of which time periods during lactation would be most appropriate to measure DMI. Aims: The aim was to evaluate whether sequence variants selected from genome-wide association studies (GWAS) for DMI recorded at multiple lactation time periods and parities would increase the accuracy of genomic estimated breeding values (GEBVs) for DMI and residual feed intake (RFI). Methods: Data of 2274 overseas lactating cows were used for the GWAS to select sequence variants. GWAS was performed using the average of the DMI phenotypes in a 30-day window of six different time periods across the lactation. The most significant sequence variants were selected from the GWAS at each time period for either first or later parities. GEBVs for DMI and RFI in Australian lactating cows were estimated using BayesRC with 50 k single nucleotide polymorphisms (SNPs) and selected GWAS sequence variants. Key results: There were differences in DMI genomic correlations and heritabilities between first and later parities and within parity across lactation time periods. Compared with using 50 k single-nucleotide polymorphisms (SNPs) only, the accuracy of DMI GEBVs increased by up to 11% by using the 50 k SNPs plus the selected sequence variants. Compared with DMI, the increase in accuracy for RFI was lower (by 6%) likely because the sequence variants were selected from GWAS for DMI not RFI. The accuracies for DMI and RFI GEBVs were highest by using selected sequence variants from the DMI GWAS in the mid- to late-lactation periods in later parity. Conclusions: Our results showed that DMI phenotypes in late lactation time periods could capture more genetic variation and increase genomic prediction accuracy through the use of custom genotype panels in genomic selection. Implications: Collecting DMI at the optimal time period(s) of lactation may help develop more accurate and cost-effective breeding values for feed efficiency in dairy cattle. Genetic improvement of feed efficiency to produce milk in dairy cattle would provide considerable economic benefits but measuring feed intake is difficult and expensive. Therefore, we used existing data to determine the best period of lactation to measure feed intake and then used advanced genomics to improve the accuracy of genomic breeding values for feed intake and efficiency. The results are an important step towards a more accurate and cost-effective approach to genetically improve dairy cow feed efficiency. [ABSTRACT FROM AUTHOR]

An obituary for professor and benefactor Michael Dunmore Monsell-Davis is presented.

Identifying causal variants for complex traits and understanding their function remain arduous tasks. A new study combines the advantages of gene mapping in livestock with elegant genetic and functional analyses to address these challenges and identifies candidate regulatory variants affecting stature in cattle. [ABSTRACT FROM AUTHOR]

Background: Causal variants for complex traits, such as eQTL are often found in non-coding regions of the genome, where they are hypothesised to influence phenotypes by regulating gene expression. Many regulatory regions are marked by histone modifications, which can be assayed by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Sequence reads from ChIP-seq form peaks at putative regulatory regions, which may reflect the amount of regulatory activity at this region. Therefore, eQTL which are also associated with differences in histone modifications are excellent candidate causal variants. Results: We assayed the histone modifications H3K4Me3, H3K4Me1 and H3K27ac and mRNA in the mammary gland of up to 400 animals. We identified QTL for peak height (histone QTL), exon expression (eeQTL), allele specific expression (aseQTL) and allele specific binding (asbQTL). By intersecting these results, we identify variants which may influence gene expression by altering regulatory regions of the genome, and may be causal variants for other traits. Lastly, we find that these variants are found in putative transcription factor binding sites, identifying a mechanism for the effect of many eQTL. Conclusions: We find that allele specific and traditional QTL analysis often identify the same genetic variants and provide evidence that many eQTL are regulatory variants which alter activity at regulatory regions of the bovine genome. Our work provides methodological and biological updates on how regulatory mechanisms interplay at multi-omics levels. [ABSTRACT FROM AUTHOR]

Empirical studies suggest that the effect sizes of individual causal risk alleles underlying complex genetic diseases are small, with most genotype relative risks in the range of 1.1-2.0. Although the increased risk of disease for a carrier is small for any single locus, knowledge of multiple-risk alleles throughout the genome could allow the identification of individuals that are at high risk. In this study, we investigate the number and effect size of risk loci that underlie complex disease constrained by the disease parameters of prevalence and heritability. Then we quantify the value of prediction of genetic risk to disease using a range of realistic combinations of the number, size, and distribution of risk effects that underlie complex diseases. We propose an approach to assess the genetic risk of a disease in healthy individuals, based on dense genome-wide SNP panels. We test this approach using simulation. When the number of loci contributing to the disease is >50, a large case-control study is needed to identify a set of risk loci for use in predicting the disease risk of healthy people not included in the case-control study. For diseases controlled by 1000 loci of mean relative risk of only 1.04, a case-control study with 10,000 cases and controls can lead to selection of ∼75 loci that explain >50% of the genetic variance. The 5% of people with the highest predicted risk are three to seven times more likely to suffer the disease than the population average, depending on heritability and disease prevalence. Whether an individual with known genetic risk develops the disease depends on known and unknown environmental factors. [ABSTRACT FROM AUTHOR]