The mosaic oat genome gives insights into a uniquely healthy cereal crop.

Cultivated oat (Avena sativa L.) is an allohexaploid (AACCDD, 2n = 6x = 42) thought to have been domesticated more than 3,000 years ago while growing as a weed in wheat, emmer and barley fields in Anatolia1,2. Oat has a low carbon footprint, substantial health benefits and the potential to replace animal-based food products. However, the lack of a fully annotated reference genome has hampered efforts to deconvolute its complex evolutionary history and functional gene dynamics. Here we present a high-quality reference genome of A. sativa and close relatives of its diploid (Avena longiglumis, AA, 2n = 14) and tetraploid (Avena insularis, CCDD, 2n = 4x = 28) progenitors. We reveal the mosaic structure of the oat genome, trace large-scale genomic reorganizations in the polyploidization history of oat and illustrate a breeding barrier associated with the genome architecture of oat. We showcase detailed analyses of gene families implicated in human health and nutrition, which adds to the evidence supporting oat safety in gluten-free diets, and we perform mapping-by-sequencing of an agronomic trait related to water-use efficiency. This resource for the Avena genus will help to leverage knowledge from other cereal genomes, improve understanding of basic oat biology and accelerate genomics-assisted breeding and reanalysis of quantitative trait studies.

A pipeline for identification of causal mutations in barley identifies Xantha-j as the chlorophyll synthase gene.

Thousands of barley (Hordeum vulgare L.) mutants have been isolated over the last century, and many are stored in gene banks across various countries. In the present work, we developed a pipeline to efficiently identify causal mutations in barley. The pipeline is also efficient for mutations located in centromeric regions. Through bulked segregant analyses using whole genome sequencing of pooled F2 seedlings, we mapped 2 mutations and identified a limited number of candidate genes. We applied the pipeline on F2 mapping populations made from xan-j.59 (unknown mutation) and xan-l.82 (previously known). The Xantha-j (xan-j) gene was identified as encoding chlorophyll synthase, which catalyzes the last step in the chlorophyll biosynthetic pathway: the addition of a phytol moiety to the propionate side chain of chlorophyllide. Key amino acid residues in the active site, including the binding sites of the isoprenoid and chlorophyllide substrates, were analyzed in an AlphaFold2-generated structural model of the barley chlorophyll synthase. Three allelic mutants, xan-j.19, xan-j.59, and xan-j.64, were characterized. While xan-j.19 is a 1 base pair deletion and xan-j.59 is a nonsense mutation, xan-j.64 causes an S212F substitution in chlorophyll synthase. Our analyses of xan-j.64 and treatment of growing barley with clomazone, an inhibitor of chloroplastic isoprenoid biosynthesis, suggest that binding of the isoprenoid substrate is a prerequisite for the stable maintenance of chlorophyll synthase in the plastid. We further suggest that chlorophyll synthase is a sensor for coordinating chlorophyll and isoprenoid biosynthesis.

Barley Viridis-k links an evolutionarily conserved C-type ferredoxin to chlorophyll biosynthesis.

Ferredoxins are single-electron carrier proteins involved in various cellular reactions. In chloroplasts, the most abundant ferredoxin accepts electrons from photosystem I and shuttles electrons via ferredoxin NADP+ oxidoreductase to generate NADPH or directly to ferredoxin dependent enzymes. In addition, plants contain other isoforms of ferredoxins. Two of these, named FdC1 and FdC2 in Arabidopsis thaliana, have C-terminal extensions and functions that are poorly understood. Here we identified disruption of the orthologous FdC2 gene in barley (Hordeum vulgare L.) mutants at the Viridis-k locus; these mutants are deficient in the aerobic cyclase reaction of chlorophyll biosynthesis. The magnesium-protoporphyrin IX monomethyl ester cyclase is one of the least characterized enzymes of the chlorophyll biosynthetic pathway and its electron donor has long been sought. Agroinfiltrations showed that the viridis-k phenotype could be complemented in vivo by Viridis-k but not by canonical ferredoxin. VirK could drive the cyclase reaction in vitro and analysis of cyclase mutants showed that in vivo accumulation of VirK is dependent on cyclase enzyme levels. The chlorophyll deficient phenotype of viridis-k mutants suggests that VirK plays an essential role in chlorophyll biosynthesis that cannot be replaced by other ferredoxins, thus assigning a specific function to this isoform of C-type ferredoxins.

A guide to barley mutants.

BACKGROUND: Mutants have had a fundamental impact upon scientific and applied genetics. They have paved the way for the molecular and genomic era, and most of today's crop plants are derived from breeding programs involving mutagenic treatments. RESULTS: Barley (Hordeum vulgare L.) is one of the most widely grown cereals in the world and has a long history as a crop plant. Barley breeding started more than 100 years ago and large breeding programs have collected and generated a wide range of natural and induced mutants, which often were deposited in genebanks around the world. In recent years, an increased interest in genetic diversity has brought many historic mutants into focus because the collections are regarded as valuable resources for understanding the genetic control of barley biology and barley breeding. The increased interest has been fueled also by recent advances in genomic research, which provided new tools and possibilities to analyze and reveal the genetic diversity of mutant collections. CONCLUSION: Since detailed knowledge about phenotypic characters of the mutants is the key to success of genetic and genomic studies, we here provide a comprehensive description of mostly morphological barley mutants. The review is closely linked to the International Database for Barley Genes and Barley Genetic Stocks ( bgs.nordgen.org ) where further details and additional images of each mutant described in this review can be found.

Patients accept therapy using embryonic stem cells for Parkinson's disease: a discrete choice experiment.

BACKGROUND: New disease-modifying ways to treat Parkinson's disease (PD) may soon become a reality with intracerebral transplantation of cell products produced from human embryonic stem cells (hESCs). The aim of this study was to assess what factors influence preferences of patients with PD regarding stem-cell based therapies to treat PD in the future. METHODS: Patients with PD were invited to complete a web-based discrete choice experiment to assess the importance of the following attributes: (i) type of treatment, (ii) aim of treatment, (iii) available knowledge of the different types of treatments, (iv) effect on symptoms, and (v) risk for severe side effects. Latent class conditional logistic regression models were used to determine preference estimates and heterogeneity in respondents' preferences. RESULTS: A substantial difference in respondents' preferences was observed in three latent preference patterns (classes). "Effect on symptoms" was the most important attribute in class 1, closely followed by "type of treatment," with medications as preferred to other treatment alternatives. Effect on symptoms was also the most important attribute in class 2, with treatment with hESCs preferred over other treatment alternatives. Likewise for class 3, that mainly focused on "type of treatment" in the decision-making. Respondents' class membership was influenced by their experience in treatment, side effects, and advanced treatment therapy as well as religious beliefs. CONCLUSIONS: Most of the respondents would accept a treatment with products emanating from hESCs, regardless of views on the moral status of embryos. Preferences of patients with PD may provide guidance in clinical decision-making regarding treatments deriving from stem cells.

A proposal for an international Code of Conduct for data sharing in genomics.

As genomic research becomes commonplace across the world, there is an increased need to coordinate practices among researchers, especially with regard to data sharing. One such way is an international code of conduct. In September 2020, an expert panel consisting of representatives from various fields convened to discuss a draft proposal formed via a synthesis of existing professional codes and other recommendations. This article presents an overview and analysis of the main issues related to international genomic research that were discussed by the expert panel, and the results of the discussion and follow up responses by the experts. As a result, the article presents as an annex a proposal for an international code of conduct for data sharing in genomics that is meant to establish best practices.

The RD-Connect Genome-Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases.

Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes.

APETALA2 control of barley internode elongation.

Many plants dramatically elongate their stems during flowering, yet how this response is coordinated with the reproductive phase is unclear. We demonstrate that microRNA (miRNA) control of APETALA2 (AP2) is required for rapid, complete elongation of stem internodes in barley, especially of the final 'peduncle' internode directly underneath the inflorescence. Disrupted miR172 targeting of AP2 in the Zeo1.b barley mutant caused lower mitotic activity, delayed growth dynamics and premature lignification in the peduncle leading to fewer and shorter cells. Stage- and tissue-specific comparative transcriptomics between Zeo1.b and its parent cultivar showed reduced expression of proliferation-associated genes, ectopic expression of maturation-related genes and persistent, elevated expression of genes associated with jasmonate and stress responses. We further show that applying methyl jasmonate (MeJA) phenocopied the stem elongation of Zeo1.b, and that Zeo1.b itself was hypersensitive to inhibition by MeJA but less responsive to promotion by gibberellin. Taken together, we propose that miR172-mediated restriction of AP2 may modulate the jasmonate pathway to facilitate gibberellin-promoted stem growth during flowering.

Would you consider donating your left-over embryos to treat Parkinson's disease? Interviews with individuals that underwent IVF in Sweden.

BACKGROUND: Parkinson's disease (PD) has been considered to be one of the most promising target diseases for forthcoming cell-based therapy. The aim of this study is to explore the views of individuals with cryopreserved embryos on using human embryonic stem cells for treating PD. METHODS: The study was performed as a qualitative, semi-structured interview study in June-October 2020. Participants were recruited at a private fertility clinic located in one of the larger Swedish cities. The clinic provides both publicly financed and privately financed IVF-treatments. All interviews were performed by telephone and analyzed using thematic content analysis. Five main categories emerged from 27 sub-categories. RESULTS: In total, 18 interviews were performed with 22 individuals, as either a couple (n = 16) or separately (n = 6). Participants had different views on what a cryopreserved embryo is. Some participants addressed cryopreserved embryos as 'a lump of cells', and some in terms of their 'unborn child'. Conditions for donation of cryopreserved embryos for cell-based treatment in PD were: not losing control of what is happening to the embryo, that donating must be voluntary and based on informed consent with time for reflection, that reimbursement, equality and transparency. CONCLUSIONS: Using cryopreserved embryos to treat PD is associated with fundamental ethical and practical issues. This study shows that IVF couples with left-over embryos may be supportive but there is a need for future research to assess people's views on using cryopreserved embryos for cell-based treatment in PD on a more aggregated level.

Patients' views on using human embryonic stem cells to treat Parkinson's disease: an interview study.

BACKGROUND: Human embryonic stem cells (hESC) as a source for the development of advanced therapy medicinal products are considered for treatment of Parkinson's disease (PD). Research has shown promising results and opened an avenue of great importance for patients who currently lack a disease modifying therapy. The use of hESC has given rise to moral concerns and been the focus of often heated debates on the moral status of human embryos. Approval for marketing is still pending. OBJECTIVE: To Investigate the perspectives and concerns of patients with PD, patients being the directly concerned stakeholders in the ethical discussion. METHODS: Qualitative semi-structured interviews related to this new therapy in seventeen patients from two Swedish cities. RESULTS: The participants expressed various interests related to the use of human embryos for development of medicinal therapies; however, overall, they were positive towards the use of hESC for treatment of PD. It was deemed important that the donating woman or couple made the choice to donate embryos voluntarily. Furthermore, there were concerns that the industry does not always prioritise the patient over profit; thus, transparency was seen as important.

Attitudes and values among the Swedish general public to using human embryonic stem cells for medical treatment.

BACKGROUND: The use of human embryonic stem cells (ES cells) for the development of medical therapies is surrounded with moral concerns. The aim of this study was to assess the public's attitudes toward the use of ES cells for treatment of Parkinson's disease (PD) and other diseases, what factors are most important to consider when using ES cells for drug development, and if there is an association between religious beliefs and attitudes toward using ES cells for medical treatment. METHODS: A randomly selected sample of the Swedish public, aged 18-87-years-old, completed an online survey (n = 467). The survey assessed socio-demographics, religious views, perceived moral status of the embryo, and attitudes toward using ES cells for medical treatment of PD and other diseases. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) for positive vs. negative attitude toward using ES cells for drug development were computed using logistic regression. RESULTS: The respondents were positive about using ES for treatment; specifically, 70% totally agreed that it is acceptable to use ES cells for treatment of PD, while 40% totally agreed that it is acceptable to use ES cells for treatment but induced pluripotent cells is just as efficient. Religion being of little importance in one's life was associated with a positive attitude toward using ES cells for treatment of PD (adjusted OR 6.39, 95% CI 2.78-14.71). The importance of being able "to access new, effective treatments against diseases that do not have any treatment available" was ranked as the most important factor to consider when using ES cells for drug development. CONCLUSION: Most respondents are positive about using ES cells for drug development, and making effective treatments accessible to those who do not have any. However, these attitudes are influenced by the specific disorder that the drug development is intended for, as well as the religious views and perceived moral status of the early embryo.

Genome-Wide Association Study of Salt Tolerance-Related Traits during Germination and Seedling Development in an Intermedium-Spike Barley Collection.

Increased salinity is one of the major consequences of climatic change affecting global crop production. The early stages in the barley (Hordeum vulgare L.) life cycle are considered the most critical phases due to their contributions to final crop yield. Particularly, the germination and seedling development are sensitive to numerous environmental stresses, especially soil salinity. In this study, we aimed to identify SNP markers linked with germination and seedling development at 150 mM NaCl as a salinity treatment. We performed a genome-wide association study (GWAS) using a panel of 208 intermedium-spike barley (H. vulgare convar. intermedium (Körn.) Mansf.) accessions and their genotype data (i.e., 10,323 SNPs) using the genome reference sequence of "Morex". The phenotypic results showed that the 150 mM NaCl salinity treatment significantly reduced all recorded germination and seedling-related traits compared to the control treatment. Furthermore, six accessions (HOR 11747, HOR 11718, HOR 11640, HOR 11256, HOR 11275 and HOR 11291) were identified as the most salinity tolerant from the intermedium-spike barley collection. GWAS analysis indicated that a total of 38 highly significantly associated SNP markers under control and/or salinity traits were identified. Of these, two SNP markers on chromosome (chr) 1H, two on chr 3H, and one on chr 4H were significantly linked to seedling fresh and dry weight under salinity stress treatment. In addition, two SNP markers on chr 7H were also significantly associated with seedling fresh and dry weight but under control condition. Under salinity stress, one SNP marker on chr 1H, 5H and 7H were detected for more than one phenotypic trait. We found that in most of the accessions exhibiting the highest salinity tolerance, most of the salinity-related QTLs were presented. These results form the basis for detailed studies, leading to improved salt tolerance breeding programs in barley.

Analysis of barley mutants ert-c.1 and ert-d.7 reveals two loci with additive effect on plant architecture.

MAIN CONCLUSION: Both mutant ert-c.1 and ert-d.7 carry T2-T3 translocations in the Ert-c gene. Principal coordinate analyses revealed the translocation types and translocation breakpoints. Mutant ert-d.7 is an Ert-c Ert-d double mutant. Mutations in the Ert-c and Ert-d loci are among the most common barley mutations affecting plant architecture. The mutants have various degrees of erect and compact spikes, often accompanied with short and stiff culms. In the current study, complementation tests, linkage mapping, principal coordinate analyses and fine mapping were conducted. We conclude that the original ert-d.7 mutant does not only carry an ert-d mutation but also an ert-c mutation. Combined, mutations in Ert-c and Ert-d cause a pyramid-dense spike phenotype, whereas mutations in only Ert-c or Ert-d give a pyramid and dense phenotype, respectively. Associations between the Ert-c gene and T2-T3 translocations were detected in both mutant ert-c.1 and ert-d.7. Different genetic association patterns indicate different translocation breakpoints in these two mutants. Principal coordinate analysis based on genetic distance and screening of recombinants from all four ends of polymorphic regions was an efficient way to narrow down the region of interest in translocation-involved populations. The Ert-c gene was mapped to the marker interval of 2_0801to1_0224 on 3HL near the centromere. The results illuminate a complex connection between two single genes having additive effects on barley spike architecture and will facilitate the identification of the Ert-c and Ert-d genes.

Analysis of early-flowering genes at barley chromosome 2H expands the repertoire of mutant alleles at the Mat-c locus.

KEY MESSAGE: Analyses of barley mat-c loss of function mutants reveal deletions, splice-site mutations and nonsynonymous substitutions in a key gene regulating early flowering. Optimal timing of flowering is critical for reproductive success and crop yield improvement. Several major quantitative trait loci for flowering time variation have been identified in barley. In the present study, we analyzed two near-isogenic lines, BW507 and BW508, which were reported to carry two independent early-flowering mutant loci, mat-b.7 and mat-c.19, respectively. Both introgression segments are co-localized in the pericentromeric region of chromosome 2H. We mapped the mutation in BW507 to a 31 Mbp interval on chromosome 2HL and concluded that BW507 has a deletion of Mat-c, which is an ortholog of Antirrhinum majus CENTRORADIALIS (AmCEN) and Arabidopsis thaliana TERMINAL FLOWER1 (AtTFL1). Contrary to previous reports, our data showed that both BW507 and BW508 are Mat-c deficient and none of them are mat-b.7 derived. This work complements previous studies by identifying the uncharacterized mat-c.19 mutant and seven additional mat-c mutants. Moreover, we explored the X-ray structure of AtTFL1 for prediction of the functional effects of nonsynonymous substitutions caused by mutations in Mat-c.

Research participants' preferences for receiving genetic risk information: a discrete choice experiment.

PURPOSE: This study aims to determine research participants' preferences for receiving genetic risk information when participating in a scientific study that uses genome sequencing. METHODS: A discrete choice experiment questionnaire was sent to 650 research participants (response rate 60.5%). Four attributes were selected for the questionnaire: type of disease, disease penetrance probability, preventive opportunity, and effectiveness of the preventive measure. Panel mixed logit models were used to determine attribute level estimates and the heterogeneity in preferences. Relative importance of the attribute and the predicted uptake for different information scenarios were calculated from the estimates. In addition, this study estimates predicted uptake for receiving genetic risk information in different scenarios. RESULTS: All characteristics influenced research participants' willingness to receive genetic risk information. The most important characteristic was the effectiveness of the preventive opportunity. Predicted uptake ranged between 28% and 98% depending on what preventive opportunities and levels of effectiveness were presented. CONCLUSION: Information about an effective preventive measure was most important for participants. They valued that attribute twice as much as the other attributes. Therefore, when there is an effective preventive measure, risk communication can be less concerned with the magnitude of the probability of developing disease.

Crosstalk among hormones in barley spike contributes to the yield.

KEY MESSAGE: The hormonal ratios along the barley spike regulate the development, atrophy and abortion of the spikelets and could be the mechanism by which the barley spike adapts its yield potential. Barley (Hordeum vulgare L.) is one of the oldest cereal crops known to be cultivated since about 10,000 years. The inflorescence of cultivated barley is an indeterminate spike that produces three single-flowered spikelets at each rachis node which make it unique among the grasses. The yield production in barley is predominantly controlled by very important parameters such as number of tillers and number of spikelets per spike. These two parameters are negatively correlated. Therefore, studying the biological and genetics of the spikelet development during the spike developmental stages is essential for breeding programs. Here we summarize our current understanding of the crosstalk between hormones such as auxin, cytokinin, gibberellin and abscisic acid along the spike and what is their role in regulating spike and spikelet development in barley. We conclude that the hormonal ratios at the apical, central, and basal sections of the spike not only regulate the spike developmental stages, but also the development, atrophy, and abortion of the spikelets. This hormonal dependent modification of the grain number along the spike could be the mechanism by which the barley spike adapts its yield potential.

Values and value conflicts in implementation and use of preconception expanded carrier screening - an expert interview study.

BACKGROUND: Endeavors have been made to found and incorporate ethical values in most aspects of healthcare, including health technology assessment. Health technologies and their assessment are value-laden and could trigger problems with dissemination if they contradict societal norms. Per WHO definition, preconception expanded carrier screening is a new health technology that warrants assessment. It is a genetic test offered to couples who have no known risk of recessive genetic diseases and are interested pregnancy. A test may screen for carrier status of several autosomal recessive diseases and X-linked at one go. The technique has been piloted in the Netherlands and is discussed in other countries. The aim of the study was to examine values and value conflicts that healthcare experts recounted in relation to the discussion of implementation and use of preconception ECS in Sweden. METHODS: We interviewed ten experts, who were associated with influencing health policymaking in Sweden. We employed systematizing expert interviews, which endeavor to access experts' specialist knowledge. There were four female and six male informants, of which four were physicians, three bioethicists, one a legal expert, one a theologian and one a political party representative in the parliament. The participants functioned as members of two non-governmental bodies and three governmental organizations. We employed thematic analysis to identify themes, categories and subcategories. RESULTS: Two main themes surfaced: values and value conflicts. The main categories of Respect for persons, Solidarity, Human dignity, Do no harm, Health and Love formed the first theme, while values conflicting with autonomy and integrity respectively, constituted the second theme. Concepts relating to respect for persons were the most commonly mentioned among the participants, followed by notions alluding to solidarity. Furthermore, respondents discussed values conflicting with Swedish healthcare ones such as equality and solidarity. CONCLUSIONS: The experts highlighted values and concepts that are distinctive of welfare states such as Sweden and delineated how preconception ECS could challenge such values. Moreover, the analysis revealed that certain values were deemed more substantive than others, judging by the extent and detail of inference; for example, respect for persons and solidarity were on top of the list.

Mutations in the gene of the Gα subunit of the heterotrimeric G protein are the cause for the brachytic1 semi-dwarf phenotype in barley and applicable for practical breeding.

BACKGROUND: Short-culm mutants have been widely used in breeding programs to increase lodging resistance. In barley (Hordeum vulgare L.), several hundreds of short-culm mutants have been isolated over the years. The objective of the present study was to identify the Brachytic1 (Brh1) semi-dwarfing gene and to test its effect on yield and malting quality. RESULTS: Double-haploid lines generated through a cross between a brh1.a mutant and the European elite malting cultivar Quench, showed good malting quality but a decrease in yield. Especially the activities of the starch degrading enzymes ß-amylase and free limit dextrinase were high. A syntenic approach comparing markers in barley to those in rice (Oryza sativa L.), sorghum (Sorghum bicolor Moench) and brachypodium (Brachypodium distachyon P. Beauv) helped us to identify Brh1 as an orthologue of rice D1 encoding the Gα subunit of a heterotrimeric G protein. We demonstrated that Brh1 is allelic to Ari-m. Sixteen different mutant alleles were described at the DNA level. CONCLUSIONS: Mutants in the Brh1 locus are deficient in the Gα subunit of a heterotrimeric G protein, which shows that heterotrimeric G proteins are important regulators of culm length in barley. Mutant alleles do not have any major negative effects on malting quality.

The Cer-cqu gene cluster determines three key players in a ß-diketone synthase polyketide pathway synthesizing aliphatics in epicuticular waxes.

Aliphatic compounds on plant surfaces, called epicuticular waxes, are the first line of defense against pathogens and pests, contribute to reducing water loss and determine other important phenotypes. Aliphatics can form crystals affecting light refraction, resulting in a color change and allowing identification of mutants in their synthesis or transport. The present study discloses three such Eceriferum (cer) genes in barley - Cer-c, Cer-q and Cer-u - known to be tightly linked and functioning in a biochemical pathway forming dominating amounts of ß-diketone and hydroxy-ß-diketones plus some esterified alkan-2-ols. These aliphatics are present in many Triticeae as well as dicotyledons such as Eucalyptus and Dianthus. Recently developed genomic resources and mapping populations in barley defined these genes to a small region on chromosome arm 2HS. Exploiting Cer-c and -u potential functions pinpointed five candidates, of which three were missing in apparent cer-cqu triple mutants. Sequencing more than 50 independent mutants for each gene confirmed their identification. Cer-c is a chalcone synthase-like polyketide synthase, designated diketone synthase (DKS), Cer-q is a lipase/carboxyl transferase and Cer-u is a P450 enzyme. All were highly expressed in pertinent leaf sheath tissue of wild type. A physical map revealed the order Cer-c, Cer-u, Cer-q with the flanking genes 101kb apart, confirming they are a gene cluster, Cer-cqu. Homology-based modeling suggests that many of the mutant alleles affect overall protein structure or specific active site residues. The rich diversity of identified mutations will facilitate future studies of three key enzymes involved in synthesis of plant apoplast waxes.

Freedom of Choice About Incidental Findings Can Frustrate Participants' True Preferences.

Ethicists, regulators and researchers have struggled with the question of whether incidental findings in genomics studies should be disclosed to participants. In the ethical debate, a general consensus is that disclosed information should benefit participants. However, there is no agreement that genetic information will benefit participants, rather it may cause problems such as anxiety. One could get past this disagreement about disclosure of incidental findings by letting participants express their preferences in the consent form. We argue that this freedom of choice is problematic. In transferring the decision to participants, it is assumed that participants will understand what they decide about and that they will express what they truly want. However, psychological findings about people's reaction to probabilities and risk have been shown to involve both cognitive and emotional challenges. People change their attitude to risk depending on what is at stake. Their mood affects judgments and choices, and they over- and underestimate probabilities depending on whether they are low or high. Moreover, different framing of the options can steer people to a specific choice. Although it seems attractive to let participants express their preferences to incidental findings in the consent form, it is uncertain if this choice enables people to express what they truly prefer. In order to better understand the participants' preferences, we argue that future empirical work needs to confront the participant with the complexity of the uncertainty and the trade-offs that are connected with the uncertain predictive value of genetic risk information.