Biology subjects

Smith, G. D.

Publications and source records attributed to Smith, G. D..

16 recordsLinked to original sources

bioRxiv2025

A blastocyst-derived in vitro model of the human chorion

The placenta supports the foetus by mediating nutrient and gas exchange, hormone production, and immune protection. Yet, human placental biology remains poorly understood due to limited in vitro models. The foetal part of the placenta, the chorion, consists of a trophoblast-derived layer and a mesenchymal zone containing extraembryonic mesoderm cells. Here, we show that human blastocysts can give rise to both trophoblast organoids and extraembryonic mesoderm cells under the same culture conditions. Trophoblast organoids originate from both outer trophoblast cells and inner cells of the blastocyst, while extraembryonic mesoderm cells derive exclusively from inner cells. These organoids recapitulate the cellular composition, morphology, and function of the in vivo trophoblast. Moreover, given the high rate of aneuploidy at the blastocyst stage, aneuploid trophoblast organoids can be readily generated. These models reflect the trophoblasts unique ability to tolerate aneuploidy and offer a valuable platform to study human placental development and pathophysiology.

developmental biology↗

bioRxiv2021

Genetic effect modification of cis-acting C-reactive protein variants in cardiometabolic disease status

Mendelian randomization (MR) studies carried out among patients with a particular health condition should establish the genetic instrument influences the exposure in that subgroup, however this is normally investigated in the general population. Here, we investigated whether the genetic associations of four cis-acting C-reactive protein (CRP) variants differed between participants with and without three cardiometabolic conditions: obesity, type 2 diabetes, and cardiovascular disease. Associations of cis-genetic variants with CRP differed between obese and non-obese individuals. A multivariable analysis suggested strong independent associations of the gene-by-body mass index (BMI) interaction on CRP (P<1.18x10-8 for the CRP variants). Applying MR, we observed strong causal effect of BMI on CRP (P=2.14x10-65). In summary, our study indicates that genetic associations with CRP differ across disease sub-groups, with evidence to suggest that BMI is an effect modifier. MR studies of disease progression should report on the genetic instrument-exposure association in the disease subgroup under investigation.

genetics↗

bioRxiv2020

Causal Inference for Heritable Phenotypic Risk Factors Using Heterogeneous Genetic Instruments

Over a decade of genome-wide association studies (GWAS) have led to the finding of extreme polygenicity of complex traits. The phenomenon that "all genes affect every complex trait" complicates Mendelian Randomization (MR) studies, where natural genetic variations are used as instruments to infer the causal effect of heritable risk factors. We reexamine the assumptions of existing MR methods and show how they need to be clarified to allow for pervasive horizontal pleiotropy and heterogeneous effect sizes. We propose a comprehensive framework GRAPPLE to analyze the causal effect of target risk factors with heterogeneous genetic instruments and identify possible pleiotropic patterns from data. By using GWAS summary statistics, GRAPPLE can efficiently use both strong and weak genetic instruments, detect the existence of multiple pleiotropic pathways, determine the causal direction and perform multivariable MR to adjust for confounding risk factors. With GRAPPLE, we analyze the effect of blood lipids, body mass index, and systolic blood pressure on 25 disease outcomes, gaining new information on their causal relationships and the potential pleiotropic pathways.

genetics↗

bioRxiv2020

Is genetic liability to ADHD and ASD causally linked to educational attainment?

BackgroundIndividuals with Attention Deficit Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder (ASD) are at risk of poor educational outcomes. Parental educational attainment has also been associated with risk of ADHD/ASD in the offspring. Despite evidence that ADHD and ASD show genetic links to educational attainment, less is known on the causal nature of the associations and the possible role of IQ. MethodsWe assessed the total causal effects of genetic liability to ADHD/ASD on educational attainment using two-sample Mendelian randomization (MR). We assessed the possible contribution of IQ to the identified causal effects by estimating the "direct" effects of ADHD/ASD on educational attainment, independent of IQ, using Multivariable MR (MVMR). Reverse direction analyses were performed. The latest GWAS meta-analyses of ADHD, ASD, educational attainment and IQ were used. Causal effect estimates were generated using inverse variance weighted models (IVW). Sensitivity analyses were performed to assess the robustness of the estimates and the presence of pleiotropy. ResultsGenetic liability to ADHD had a total (MRIVW:-3.3 months per doubling of liability to ADHD; 95%CI: -4.8 to -1.9; pval= 5*10-6) and direct negative causal effect on educational attainment (MVMRIVW:-1.6 months per doubling of liability to ADHD; 95%CI: -2.5 to -0.6; pval= 4*10-4). There was little evidence of a total causal effect of genetic liability to ASD on educational attainment (MRIVW: 4 days, per doubling of liability to ASD; 95%CI: -4.9 months to 5.6 months; pval= 0.9) but some evidence of a direct effect not via IQ (MVMRIVW:29 days per doubling the genetic liability to ASD; 95%CI: 2 to 48; pval= 0.03). Reverse direction analyses suggested that genetic liability to higher educational attainment was associated with lower risk of ADHD (MRIVWOR: 0.3 per standard deviation (SD) increase; 95%CI: 0.26 to 0.36; pval= 6*10-51), even after IQ was entered in the models (MVMRIVWOR: 0.33 per SD increase; 95%CI: 0.26 to 0.43; pval= 6*10-17). On the contrary, there was evidence consistent with a positive causal effect of genetic liability to higher educational attainment on risk of ASD (MRIVWOR: 1.51 per SD increase; 95%CI: 1.29 to 1.77; pval= 4*10-7), which was found to be largely explained by IQ (MVMRIVWOR per SD increase: 1.24; 95%CI: 0.96 to 1.60; pval= 0.09). ConclusionsOur findings suggest that despite the genetic and phenotypic overlap between ADHD and ASD, they present highly differentiated causal associations with educational attainment. This highlights the necessity for specialized educational interventions for children with ADHD and ASD. Further research is needed in order to decipher whether the identified causal effects reflect parentally transmitted effects, diagnostic masking, or selection bias.

genetics↗

bioRxiv2020

Slope-Hunter: A robust method for index-event bias correction in genome-wide association studies of subsequent traits

BackgroundStudying genetic associations with prognosis (e.g. survival, disability, subsequent disease events) is problematic due to selection bias - also termed index event bias or collider bias - whereby selection on disease status can induce associations between causes of incidence with prognosis. A current method for adjusting genetic associations for this bias assumes there is no genetic correlation between incidence and prognosis, which may not be a plausible assumption. MethodsWe propose an alternative, the Slope-Hunter approach, which is unbiased even when there is genetic correlation between incidence and prognosis. Our approach has two stages. First, we use cluster-based techniques to identify: variants affecting neither incidence nor prognosis (these should not suffer bias and only a random sub-sample of them are retained in the analysis); variants affecting prognosis only (excluded from the analysis). Second, we fit a cluster-based model to identify the class of variants only affecting incidence, and use this class to estimate the adjustment factor. ResultsSimulation studies showed that the Slope-Hunter method reduces type-1 error by between 49%-85%, increases power by 1%-36%, reduces bias by 17%-47% compared to other methods in the presence of genetic correlation and performs as well as previous methods when there is no genetic correlation. Slope-Hunter and the previous methods perform less well as the proportion of variation in incidence explained by genetic variants affecting only incidence decreases. ConclusionsThe key assumption of Slope-Hunter is that the contribution of the set of genetic variants affecting incidence only to the heritability of incidence is at least as large as the contribution of those affecting both incidence and prognosis. When this assumption holds, our approach is unbiased in the presence of genetic correlation between incidence and progression, and performs no worse than alternative approaches even when there is no correlation. Bias-adjusting methods should be used to carry out causal analyses when conditioning on incidence.

genetics↗

bioRxiv2019

Identifying epigenetic biomarkers of established prognostic factors and survival in a clinical cohort of individuals with oropharyngeal cancer

Smoking status, alcohol consumption and HPV infection (acquired through sexual activity) are the predominant risk factors for oropharyngeal cancer and are thought to alter the prognosis of the disease. Here, we conduct epigenome-wide association studies (EWAS) of these factors and [~]3-year survival using Illumina Methylation EPIC blood DNA methylation profiles from 409 individuals in the Head and Neck 5000 (HN5000) study. CpG site associations below our multiple-testing threshold (PBonferroni < 0.05) with both a prognostic factor and with survival were observed in four gene regions: SPEG (smoking), GFI1 (smoking), PPT2 (smoking), and KHD3CL (alcohol consumption). These were further analysed using 2-step Mendelian randomization to assess whether methylation may be a causal mediator of cancer survival. Evidence for mediation was observed only in the SPEG gene region, showing an association with decreased survival (mortality HR: 1.28, 95% CI: 1.14 to 1.43, P: 2.12x10-05). Replication in data from independent datasets, and from HN5000 participants with longer follow-up times is needed to confirm these findings.

epidemiology↗

bioRxiv2019

Antisense oligonucleotide therapy rescues aggresome formation in a novel Spinocerebellar Ataxia type 3 human embryonic stem cell line.

Spinocerebellar ataxia type 3 (SCA3) is a fatal, late-onset neurodegenerative disorder characterized by selective neuropathology in the brainstem, cerebellum, spinal cord, and substantia nigra. Here, we characterize the first NIH-approved human embryonic stem cell (hESC) line derived from an embryo harboring the SCA3 mutation. Referred here as SCA3-hESC, this line is heterozygous for the mutant polyglutamine-encoding CAG repeat expansion in the ATXN3 gene within the pathogenic repeat range for SCA3. We observed relevant molecular hallmarks of the human disease at all differentiation stages from stem cells to cortical neurons, including robust ATXN3 aggregation and altered expression of key components of the protein quality control machinery. Finally, antisense oligonucleotide-mediated reduction of ATXN3 prevented the formation of p62-positive aggresomes in SCA3-hESCs. The SCA3-hESC line offers a unique and highly relevant human disease model that holds strong potential to advance understanding of SCA3 disease mechanisms and facilitate the evaluation of possible SCA3 therapies.\n\nHighlightsO_LIGenerated first NIH-approved SCA3 human embryonic stem cell line (SCA3-hESC)\nC_LIO_LISCA3-hESC exhibit robust ATXN3 aggregation pathology and form p62+ aggresomes\nC_LIO_LIAnti-ATXN3 antisense oligonucleotides rescue aggresome formation in SCA3-hESC\nC_LIO_LIDerived SCA3 neurons form aggregates and exhibit impaired protein quality control\nC_LI

neuroscience↗

bioRxiv2018

Investigating the combined association of BMI and alcohol consumption on liver disease and biomarkers: a Mendelian randomization study of over 90 000 adults from the Copenhagen General Population Study

BackgroundBody mass index (BMI) and alcohol consumption are suggested to independently and interactively increase the risk of liver disease. We assessed this combined effect using factorial Mendelian randomization (MR).\n\nMethodsWe used multivariable adjusted regression and MR to estimate individual and joint associations of BMI and alcohol consumption and liver disease biomarkers (alanine aminotransferase (ALT) y-glutamyltransferase (GGT)) and incident liver disease. We undertook a factorial MR study splitting participants by median of measured BMI or BMI allele score then by median of reported alcohol consumption or ADH1B genotype (AA/AG and GG), giving four groups; low BMI/low alcohol (-BMI/-alc), low BMI/high alcohol (-BMI/+alc), high BMI/low alcohol (+BMI/-alc) and high BMI/high alcohol (+BMI/+alc).\n\nResultsIndividual positive associations of BMI and alcohol with ALT, GGT and incident liver disease were found. In the factorial MR analyses, considering the +BMI/+alc group as the reference, mean circulating ALT and GGT levels were lowest in the -BMI/-alc group (2.32% (95% CI: -4.29, -0.35) and -3.56% (95% CI: -5.88; -1.24) for ALT and GGT respectively). Individuals with -BMI/+alc and +BMI/-alc had lower mean circulating ALT and GGT compared to the reference group (+BMI/+alc). For incident liver disease multivariable factorial analyses followed a similar pattern to those seen for the biomarkers, but little evidence of differences between MR factorial categories for odds of liver disease.\n\nConclusionsConsistent results from multivariable regression and MR analysis, provides compelling evidence for the individual adverse effects of BMI and alcohol consumption on liver disease. Intervening on both BMI and alcohol may improve the profiles of circulating liver biomarkers. However, this may not reduce clinical liver disease risk.

epidemiology↗

bioRxiv2018

Targeted Reactivation of FMR1 Transcription in Fragile X Syndrome Embryonic Stem Cells

Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability and autism. It results from expansion of a CGG nucleotide repeat in the 5 untranslated region of FMR1. Large expansions elicit repeat and promoter hyper-methylation, heterochromatin formation, FMR1 transcriptional silencing, and loss of the Fragile X protein, FMRP. Efforts aimed at correcting the sequelae resultant from FMRP loss have thus far proven insufficient, perhaps because of FMRPs pleiotropic functions. As the repeats do not disrupt the FMRP coding sequence, reactivation of endogenous FMR1 gene expression could correct the proximal event in FXS pathogenesis. Here we utilize the CRISPR/dCAS9 system to selectively re-activate transcription from the silenced FMR1 locus. Fusion of the transcriptional activator VP192 to dCAS9 robustly enhances FMR1 transcription and increases FMRP levels when targeted directly to the CGG repeat in human cells. Using a previously uncharacterized FXS human embryonic stem cell (hESC) line which acquires transcriptional silencing with serial passaging, we achieved locus-specific transcriptional re-activation of FMR1 mRNA expression despite promoter and repeat methylation. These studies demonstrate that FMR1 mRNA expression can be selectively reactivated in human patient cells, creating a pathway forward for therapeutic development in Fragile X Syndrome.

neuroscience↗

bioRxiv2018

Evidence of a common causal relationship between body mass index and inflammatory skin disease: a Mendelian Randomization study

ObjectivePsoriasis and eczema are common inflammatory skin diseases that have been reported to be associated with obesity. However, causality has not yet been established. We aimed to investigate the possible causal relationship between body mass index (BMI) and psoriasis or eczema.\n\nMethodsFollowing a review of published epidemiological evidence of the association between obesity and either psoriasis or eczema, Mendelian Randomization (MR) was used to test for a causal relationship between BMI and these inflammatory skin conditions. We used a genetic instrument comprising 97 single nucleotide polymorphisms (SNPs) associated with BMI. One-sample MR was conducted using individual-level data (401,508 individuals) from the UK Biobank and the Nord-Trondelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (731,021 individuals) from published BMI, psoriasis and eczema GWAS. The one-sample and two-sample MR estimates were meta-analysed using a fixed effect model. To explore the reverse causal direction, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis and eczema were used to test if inflammatory skin disease has a causal effect on BMI.\n\nResultsPublished observational data show an association of greater BMI with both psoriasis and eczema case status. The observational associations were confirmed in UK Biobank and HUNT datasets. MR analyses provide evidence that higher BMI causally increases the odds of psoriasis (by 53% per 5 units higher BMI; OR= 1.09 (1.06 to 1.12) per 1 kg/m2; P=4.67x10-9) and eczema (by 8% per 5 units higher BMI; OR=1.02 (1.00 to 1.03) per 1 kg/m2; P=0.09). When investigating causality in the opposite direction, MR estimates provide little evidence for an effect of either psoriasis or eczema influencing BMI.\n\nConclusionOur study, using genetic variants as instrumental variables for BMI, shows that higher BMI leads to a higher risk of inflammatory skin disease. The causal relationship was stronger for psoriasis than eczema. Therapies and life-style interventions aimed at controlling BMI or targeting the mechanisms linking obesity with skin inflammation may offer an opportunity for the prevention or treatment of these common skin diseases.

genetics↗

bioRxiv2017

Causal inference in cancer epidemiology: what is the role of Mendelian randomization?

Observational epidemiological studies are prone to confounding, measurement error, and reverse causation, undermining their ability to generate reliable causal estimates of the effect of risk factors to inform cancer prevention and treatment strategies. Mendelian randomization (MR) is an analytical approach that uses genetic variants to proxy potentially modifiable exposures (e.g. environmental factors, biological traits, and druggable pathways) to permit robust causal inference of the effects of these exposures on diseases and their outcomes. MR has seen widespread adoption within population health research in cardio-metabolic disease, but also holds much promise for identifying possible interventions (e.g., dietary, behavioural, or pharmacological) for cancer prevention and treatment. However, some methodological and conceptual challenges in the implementation of MR are particularly pertinent when applying this method to cancer aetiology and prognosis, including reverse causation arising from disease latency and selection bias in studies of cancer progression. These issues must be carefully considered to ensure appropriate design, analysis, and interpretation of such studies.\n\nIn this review, we provide an overview of the key principles and assumptions of MR focusing on applications of this method to the study of cancer aetiology and prognosis. We summarize recent studies in the cancer literature that have adopted a MR framework to highlight strengths of this approach compared to conventional epidemiological studies. Lastly, limitations of MR and recent methodological developments to address them are discussed, along with the translational opportunities they present to inform public health and clinical interventions in cancer.

epidemiology↗

bioRxiv2017

Circulating selenium and prostate cancer risk: a Mendelian randomization analysis

In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 g/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic risk score comprising eleven single-nucleotide polymorphisms robustly (P<5x10-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72,729 men in the PRACTICAL Consortium (44,825 cases, 27,904 controls), 114 g/L higher genetically-elevated circulating selenium was not associated with prostate cancer (OR: 1.01; 95% CI: 0.89-1.13). Concordant with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR: 1.21; 95% CI: 0.98-1.49) and type 2 diabetes (OR: 1.18; 95% CI: 0.97-1.43; in a type 2 diabetes GWAS meta-analysis with up to 49,266 cases, 249,906 controls). Mendelian randomization mirrored the outcome of selenium supplementation in SELECT and may offer an approach for the prioritization of interventions for follow-up in large-scale randomized controlled trials.

epidemiology↗

bioRxiv2017

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, United Kingdom, and United States, comprising a total of 52,506 phenotyped individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs at a genome-wide level of significance in KITLG, DOCK8, and a broad region of 9q32. In a bivariate analysis combining the nevus results with those from a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level of significance. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis via genes we can show to be expressed under control of the MITF melanocytic cell lineage regulator.

genetics↗

bioRxiv2017

A likelihood ratio test for changes in homeolog expression bias

Background: Gene duplications are a major source of raw material for evolution and a likely contributor to the diversity of life on earth. Duplicate genes (i.e., homeologs, in the case of a whole genome duplication) may retain their ancestral function, sub- or neofunctionalize, or be lost entirely. A primary way that duplicate genes may evolve new functions is by altering their expression patterns. Comparing the expression patterns of duplicate genes may give clues as to whether any of these evolutionary processes have occurred.\n\nResults: We develop a likelihood ratio test for the analysis of the expression ratios of duplicate genes across two conditions (e.g., tissues). We demonstrate an application of this test by comparing homeolog expression patterns of 1,448 homeologous gene pairs using RNA-seq data generated from the leaves and petals of an allotetraploid monkeyflower (Mimulus luteus). We assess the sensitivity of this test to different levels of homeolog expression bias and compare the method to several alternatives.\n\nConclusions: The likelihood ratio test derived here is a direct, transparent, and easily implemented method for detecting changes in homeolog expression bias that outperforms three alternative approaches. While our method was derived with homeolog analysis in mind, this method can be used to analyze changes in the ratio of expression levels between any two genes in any two conditions.

genomics↗

bioRxiv2017

Association of pre-pregnancy body mass index with future offspring metabolic profile: findings from three independent European birth cohorts

BackgroundA high proportion of women start pregnancy overweight/obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives, and, thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) with offspring systemic metabolite profile are causal via intrauterine mechanisms or familial factors.\n\nMethods and FindingsWe used one and two-stage individual participant data (IPD) metaanalysis, and a negative-control (paternal BMI) to examine the association between maternal prepregnancy BMI and offspring serum metabolome from three European birth cohorts (offspring age at metabolite assessment 16, 17 and 31 years). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from one-stage IPD meta-analysis (N=5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with VLDL-lipoproteins, VLDL-C, VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with HDL-lipoprotein, HDL-diameter, HDL-C, HDL2-C and HDL3-C (all P<0.003). Stronger magnitudes of associations were present for maternal compared with paternal BMI across these associations, however there was no strong statistical evidence for heterogeneity between them (all bootstrap P >0.003, equivalent to 0.05 after accounting for multiple testing). Results were similar in each individual cohort, and in the two-stage analysis. Offspring BMI showed similar patterns of crosssectional association with metabolic profiles as for parental pre-pregnancy BMI associations, but with greater magnitudes. Adjustment of the parent BMI-offspring metabolite associations for offspring BMI suggested the parental associations were largely due to the association of parental BMI measures with offspring BMI.\n\nConclusionOur findings suggest that maternal BMI-offspring metabolome associations are likely to be largely due to shared genetic or familial lifestyle confounding, rather than intrauterine programming mechanisms. They do not support the introduction of measures to reduce maternal BMI in order to prevent adverse offspring cardio-metabolic health.

epidemiology↗

bioRxiv2016

Subgenome dominance in an interspecific hybrid, synthetic allopolyploid, and a 140 year old naturally established neo-allopolyploid monkeyflower.

The importance and applications of polyploidy have long been recognized, from shaping the evolutionary success of flowering plants to improving agricultural productivity. Recent studies have shown that one of the parental subgenomes in ancient polyploids is generally more dominant - having both retained more genes and being more highly expressed - a phenomenon termed subgenome dominance. How quickly one subgenome dominates within a newly formed polyploid, if immediate or after millions of years, and the genomic features that determine which genome dominates remain poorly understood. To investigate the rate of subgenome dominance emergence, we examined gene expression, gene methylation, and transposable element (TE) methylation in a natural less than 140 year old allopolyploid (Mimulus peregrinus), a resynthesized interspecies triploid hybrid (M. robertsii), a resynthesized allopolyploid (M. peregrinus), and diploid progenitors (M. guttatus and M. luteus). We show that subgenome expression dominance occurs instantly following the hybridization of two divergent genomes and that subgenome expression dominance significantly increases over generations. Additionally, CHH methylation levels are significantly reduced in regions near genes and within transposons in the first generation hybrid, intermediate in the resynthesized allopolyploid, and are repatterned differently between the dominant and submissive subgenomes in the natural allopolyploid. Our analyses reveal that the subgenome differences in levels of TE methylation mirror the increase in expression bias observed over the generations following the hybridization. These findings not only provide important insights into genomic and epigenomic shock that occurs following hybridization and polyploid events, but may also contribute to uncovering the mechanistic basis of heterosis and subgenomic dominance.

genomics↗