Biology subjects

Soller, M.

Publications and source records attributed to Soller, M..

At least 19 recordsLinked to original sources

bioRxiv2026

LARP1-DM15/Sgt is a reader for cap-adjacent 2`-O-ribose methylation in TOP ribosomal protein mRNAs required for localization to synapses

The most prominent mRNA modification in animals and many of their parasites is 2`-O-ribose methylation of cap-adjacent nucleotides (cOMe) introduced by cap-methyl transferases (CMTrs). How these modifications impact on gene expression and are decoded by reader proteins, however, remains uncertain. Through analysis of transcriptional start-site usage, we discovered a bias in ribosomal protein mRNAs starting with the Terminal Oligo Pyrimidine (TOP) motif, but not other TOP mRNAs in the absence of cOMe. cOMe stabilizes TOP mRNAs, enhances binding of the LARP1-DM15 domain to the TOP mRNA 5` end and is assisted by the tetratricopeptide domain-containing protein Sgt/SGTA/B. This conserved complex is required for localization of TOP ribosomal protein mRNAs to Drosophila synapses. Our study reveals an mRNA methylation-mediated mechanism to maintain local protein synthesis remote from the nucleus for sustained synaptic functions.

molecular biology↗

bioRxiv2026

decepentaplegic directs the wiring of female-differentiated fruitless sex peptide response-inducing neurons

Female reproductive success requires coordinated behavioural responses following mating. In Drosophila melanogaster, these responses are induced by male-derived sex-peptide (SP) and include reduced receptivity to further mating and increased oviposition. Although the neural pathways controlling these behaviours have been partially characterized, the developmental mechanisms that establish and maintain these circuits remain poorly understood. Using a genetic approach, we identified an EMS-induced mutant that retains eggs and fails to reduce receptivity following SP exposure. We mapped this mutation to the transcription termination zone after the polyA site of the dpp locus and show that this allele dppHB3 affects expression. Dpp/BMP signalling acts within SP response-inducing neurons (SPRINz) and is required for correct neuronal wiring in dppHB3 mutants. We further find that the SPRINZ-fru11/12 enhancer induces gene expression upon Dpp exposure. Also, female sexual differentiation trough the sex determination gene tra is required in SPRINz to display post-mating behaviours. Together, these findings suggest a new role for dpp in specifying neuronal connectivity in the context of sexual differentiation by the Drosophila canonical sex determination pathway to implement neuronal wiring for post-mating behaviours.

genetics↗

bioRxiv2025

Is it chaotic? Chicken Linkage Disequilibrium and quantitative trait loci

Linkage disequilibrium (LD) underpins genome-wide association studies (GWAS) to map Quantitative Trait Loci Regions (QTLRs). A common yet misled assumption is that the closest sites to a significant marker are the prime candidates as the causative mutation. However, LD blocks are typically fragmented and intermingled. We studied chicken LD of mapped QTLRs for Mareks Disease in numerous chicken populations. We estimated background LD by random sampling of non-syntenic or syntenic marker pairs from different or same chromosomes. We defined LD blocks as a group of markers located on the same chromosome having significant moderate (0.15 [≥] r2 < 0.7) or high (r2 [≥] 0.7) LD, regardless of distance and the number of mixed markers with no LD. Next, we studied QTLR LD by all SNP markers within the QTLRs. We found very complex, nearly chaotic, LD patterns, with fragmented and interdigitated LD blocks. Exceptional LD was found between QTLRs 4-5. LD blocks and protein networks shared by the two QTLRs suggest possible functional relationships. Thus, potential causative candidates could be found beyond non-LD sites, occasionally at a very large distance from a significant marker, and even in another QTLR. Multiple effects might make LD intrinsically chaotic, thus limiting GWAS informativity and repeatability. Chaotic complexity challenges the practical use of LD across populations, and must be accounted for while interpreting genetic mapping studies.

genetics↗

bioRxiv2025

Stochastic splicing and deterministic inclusion of exon variables promote diversification of Down Syndrome Cell Adhesion Molecule expression

Mutually alternative splicing in Down Syndrome Cell Adhesion Molecule (Dscam) gene of arthropods generates extraordinary molecular diversity producing tens of thousands of isoforms. From three clusters of variable exons directing homophilic interactions, one single exon is selected. Homophilic repulsion of identical isoforms directs branching of axons running in neuronal tracts, and of dendrites for generation of overlapping dendritic fields through selection of different variants in neighbouring cells. Here, we investigate the spatial inclusion of Dscam alternative exons in Drosophila and honey bees using reporter genes and in situ hybridizations, respectively. In Drosophila, we find that Dscam variable clusters 4 and 9 splicing is not always productive in reporters, resulting in suppressed expression in optic lobes and variable expression across identical cells in salivary glands and photoreceptor fields. However, in photoreceptor neurons in larvae, we find repetitive inclusion of specific variants suggesting that stochastic expression is generated at the level of splicing of the variable cluster, but inclusion of variants follows a deterministic path. Likewise, we find in larval brains, inclusion of exon 4 and 9 variants in compartmentalised and repetitive patterns. In foraging honey bees, inclusion of exon 4 and 10 variants occurs in compartmentalised patterns differing between mushroom body lobes and individuals. This indicates that initial equal inclusion of exon variants is directed to compartmentalised inclusion through experience. These findings detail a new model of experience directed alternative splicing in Dscam incorporating stochasticity through splicing productivity and deterministic selection of individual isoforms.

molecular biology↗

bioRxiv2025

Assessing species-specific neonicotinoid toxicity using cross-species chimeric nicotinic acetylcholine receptors in a Drosophila model

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels and the main mediators of synaptic neurotransmission in the insect brain. In insects, nAChRs are pivotal for sensory processing, cognition and motor control, and are the primary target of neonicotinoid insecticides. Neonicotinoids are potent neurotoxins and pollinators such as honey bees are more sensitive and affected by extremely low sub-lethal doses. The pentameric nAChR channel is made up either of five -subunits constituting five ligand-binding sites or a mixture of two to three and {beta} subunits constitute two to three ligand-binding sites. Of particular note, the honey bee nAChR8 subunit is converted into a {beta} subunit (nAChR{beta}2) in Drosophila, raising the question whether this to {beta} conversion makes flies less sensitive to neonicotinoids. To investigate species-specific aspects of neonicotinoid toxicity we CRISPR-Cas9 engineered a cross-species chimeric nAChR subunit by swapping the ligand-binding domain in Drosophila of nAChR{beta}2 with honey bee nAChR8. Toxicity assessment by neonicotinoid thiamethoxam revealed significantly impaired motor functions in climbing and flight assays when comparing the 8/{beta}2 chimeric channel to wild type or a {beta}2 knock-out. However, both the 8/{beta}2 chimeric channel and the {beta}2 knock-out showed the same increased survival after neonicotinoid exposure compared to wild type flies. Combinatorial exposure to neonicotinoids also did not reveal differences. These findings highlight the critical role of nAChR subunit composition in motor control and demonstrate how subtle structural differences can profoundly impact motor function and pesticide response, offering new insights into the molecular mechanisms of neurotoxicity across species.

molecular biology↗

bioRxiv2025

TET dioxygenases localize at splicing speckles and promote RNA splicing

The dynamic regulation of RNA metabolism plays a crucial part in cellular function, with emerging evidence suggesting an important role for RNA modifications in this process. This study explores the relationship between RNA splicing and the TET dioxygenase activity, shedding light on the role of hm5C (RNA 5-hydroxymethylcytosine), and TET proteins, in RNA metabolism. Integrating data from mass spectrometry, AlphaFold structural modeling, microscopic analysis, and different functional assays including in vitro splicing, TET proteins were found to regulate splicing. We show that TET1, TET2, and TET3 interact with the splicing factors U2AF1 and U2AF2. Interestingly, TET dioxygenases localize in splicing speckles in mammalian and Drosophila cells. TET speckles association is RNA dependent, as it is TET interaction with splicing factors. Furthermore, in vitro splicing assays revealed that all three TET proteins promote splicing efficiency, and the oxidation of m5C to hm5C can restore splicing efficiency in vitro. The latter highlights the regulatory role of cytosine modifications in RNA metabolism. These findings provide insights into the complex interplay between RNA modifications and splicing, suggesting a multifaceted role for TET proteins in RNA metabolism beyond its canonical DNA demethylation function. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/641893v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1a304bborg.highwire.dtl.DTLVardef@18b91d3org.highwire.dtl.DTLVardef@12efeforg.highwire.dtl.DTLVardef@1464355_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- TET1 localizes in splicing speckles in an RNA-dependent manner - TET proteins, especially TET1, interact with the splicing factors U2AF1 and U2AF2 - TET proteins increase splicing efficiency, independent of their catalytic activity - RNA 5-methylcytosine (m5C) oxidation to 5-hydroxymethylcytosine (hm5C) restores splicing efficiently in vitro

cell biology↗

bioRxiv2025

Cap-adjacent 2'-O-ribose methylation of RNA in C. elegans is required for postembryonic growth and germline development in the presence of the decapping exonuclease EOL-1

Cap-adjacent 2-O-ribose methylation (cOMe) of the first two transcribed nucleotides of RNA polymerase II transcripts is a conserved feature in many eukaryotes. In mammals, these modifications are key to a transcript surveillance system that regulates the interferon response, but the broader functions of cOMe remain poorly understood. To understand the role of cOMe in C. elegans, we functionally characterised the methyltransferases (CMTR-1 and CMTR-2) responsible for installing these modifications. These enzymes have distinct expression patterns, protein interaction partners, and loss of function phenotypes. Loss of CMTR-1 causes dramatic reductions in cOMe, impaired growth and sterility. In contrast, animals lacking CMTR-2 are superficially wild-type, though CMTR-2 loss enhances the severity of the cmtr-1 mutant phenotype. Depletion of CMTR-1 causes downregulation of transcripts associated with germline sex determination and upregulation of those involved in the intracellular pathogen response (IPR). We show that absence of the decapping exonuclease, EOL-1, an IPR component, completely suppresses the sterility and growth defects caused of loss of CMTR-1, suggesting that EOL-1 degrades cellular transcripts lacking cOMe. Our work shows the physiological relevance of cOMe in protecting transcripts from decapping exonucleases, raising the possibility that cOMe plays a role in RNA-mediated immune surveillance beyond the vertebrates. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/638824v2_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1cd906dorg.highwire.dtl.DTLVardef@c4e922org.highwire.dtl.DTLVardef@1a5c2dborg.highwire.dtl.DTLVardef@19be5d8_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2024

DOA/CLK2 phosphorylates Fl(2)d/WTAP to enhance m6A mRNA methyltransferase complex activity

N6-methyladenosine (m6A) is the most abundant internal modification in messenger RNA (mRNA) providing an essential layer to the control of gene expression important to many biological processes. A megadalton writer complex deposits m6A methyl marks that are then read by YTH domain containing proteins. Deposition of m6A is thought to be regulated by cellular signalling but how remains uncertain. We identified the kinase DOA, a highly conserved homologue of human CLK2 by using the essential role of m6A in the Drosophila Sxl auto-regulation for sex determination and dosage compensation. We show that DOA kinase is required for m6A deposition and Sxl alternative splicing. Overexpression of DOA can compensate writer complex insufficiency and rescue lethality of m6A in the context of Sxl mis- splicing, suggesting a key role in regulating activity of the m6A complex. Through genetic interaction experiments, we identify a phospho-site at the end of a conserved helical structure in Fl(2)d as DOA target. CLK2 phosphorylates the same helix in WTAP, the human homologue of Fl(2)d. CLK2 expands regulatory capacity through additional phospho-sites and changing of the Drosophila site to a phosphomimetic-like glutamine, overall important for m6A directed regulation of dosage compensation genes in human cells.

genetics↗

bioRxiv2024

Rapid promoter evolution of male accessory gland genes is accompanied by divergent expression in closely related Drosophila species

Seminal fluid proteins (Sfps) are essential for reproductive success and evolve fast, possibly driven by post-copulatory sexual selection (PCSS) originating from sperm competition and cryptic female choice. Counterintuitively, however, the coding region only in few Sfps evolves adaptively. Hence, additional genomic and functional factors must play a role in Sfp evolution independent of the protein coding region. To shed light on drivers of Sfp evolution we focus on those Sfps predominantly expressed in male accessory glands, because this allows examination of their evolution in the tissue which produces the majority of Sfps. Moreover, accessory glands develop normally in hybrids in contrast to testis allowing to control for changes in cellular environment arising during speciation. Here, we discover that Acp promoters contain hot spots for rapid evolution from accumulation of sequence changes and insertions/deletions (indels). We further show that changes in promoter sequences are accompanied by gene expression divergence among closely related Drosophila species. We then validate these observations in Drosophila hybrids to show that species-specific expression divergence of Acps with rapidly evolving promoters are maintained in hybrids for some Acps, while others show dominance of one allele, a phenomenon termed transvection. These results indicate that cis-regulatory evolution, rather than genome background variation, drives Acp expression changes and promotes their rapid evolution.

evolutionary biology↗

bioRxiv2024

Sex-peptide targets distinct higher order processing neurons in the brain to induce the female post-mating response

Sex-peptide (SP) transferred during mating induces female post-mating responses including refractoriness to re-mate and increased oviposition in Drosophila. Yet, where SP-target neurons reside, remained uncertain. Here we show that expression of membrane-tethered SP (mSP) pre-dominantly in the head or trunk either reduces receptivity or increases oviposition, respectively. Using fragments from large regulatory regions of Sex Peptide Receptor, fruitless and doublesex genes together with intersectional expression of mSP, we identified distinct interneurons in the brain and abdominal ganglion controlling receptivity and oviposition. These SP Response Inducing Neurons (SPRINz) can induce post-mating responses through SP received by mating. Trans-synaptic mapping of neuronal connections reveals input from sensory processing neurons and two post-synaptic trajectories as output. Hence, SP-target neurons operate as key integrators of sensory information for decision of behavioural outputs. Multi-modularity of SP-targets further allows females to adjust SP-mediated male manipulation to physiological state and environmental conditions for maximizing reproductive success.

neuroscience↗

bioRxiv2023

Promoters of germline transposon silencing genes evolve rapidly accompanied by diverging gene expression

BackgroundThe piRNA pathway in animal gonads functions as an RNA-based immune system, serving to silence transposable elements and prevent inheritance of novel invaders. In Drosophila, this pathway relies on three gonad-specific Argonaute proteins (Argonaute-3, Aubergine and Piwi) that associate with 23-28 nucleotide piRNAs, directing the silencing of transposon-derived transcripts. Transposons constitute a primary driver of genome evolution, yet the evolution of piRNA pathway factors has not received in-depth exploration. Specifically, channel nuclear pore proteins, which impact piRNA processing, exhibit regions of rapid evolution in their promoters. Consequently, the question arises whether such a mode of evolution is a general feature of transposon silencing pathways. ResultsBy employing genomic analysis of coding and promoter regions within genes that function in transposon silencing in Drosophila, we demonstrate that the promoters of germ cell-specific piRNA factors are undergoing rapid evolution. Our findings indicate that rapid promoter evolution is a common trait among piRNA factors engaged in germline silencing across insect species, potentially contributing to gene expression divergence in closely related taxa. Furthermore, we observe that the promoters of genes exclusively expressed in germ cells generally exhibit rapid evolution, with some divergence in gene expression. ConclusionOur results suggest that increased germline promoter evolution, in partnership with other factors, could contribute to transposon silencing and evolution of species through differential expression of genes driven by invading transposons.

evolutionary biology↗

bioRxiv2023

Memory consolidation in honey bees is enhanced by down-regulation of Down Syndrome Cell Adhesion Molecule and changes its alternative splicing

Down syndrome cell adhesion molecule (Dscam) gene encodes a cell adhesion molecule required for neuronal wiring. A remarkable feature of invertebrate Dscam is massive alternative splicing generating thousands of different isoforms from three variable clusters of alternative exons. Dscam expression and diversity arising from alternative splicing have been studied during development, but whether they exert functions in differentiated brains has not been determined. Here, using honey bees, we find that Dscam expression is critically linked to memory retention as reducing expression by RNAi enhances memory after reward learning in adult worker bees. Moreover, alternative splicing of Dscam is altered in all three variable clusters after learning. Since identical Dscam isoforms engage in homophilic interactions, these results suggest a mechanism to alter inclusion of variable exons during memory consolidation to modify neuronal connections for memory retention.

neuroscience↗

bioRxiv2023

Indel driven rapid evolution of core nuclear pore protein gene promoters

Nuclear pore proteins (Nups) prominently are among the few genes linked to speciation from hybrid incompatibility in Drosophila. It was previously found that neuronal wiring underlying the female post-mating response induced by male-derived sex-peptide requires channel Nup54 functionality. A hot spot for rapid evolution in the promoter of Nup54 suggests a critical role for regulatory elements at the onset of speciation. Systematic analysis of Nup coding and promoter regions using Drosophila phylogenomics reveals that polymorphism differences between closely related Drosophila species in Nup coding regions do not generally evolve rapidly. Consistent with findings for Nup54, additional channel Nups 58 and 62 promotors are also hotpots for rapid accumulation of insertions/deletions (indels). Examination of Nup upstream regions reveals that core nuclear pore complex gene promoters accumulate indels rapidly. Since changes in promoters can have dominant effects (effects which directly impact gene expression of associated genes), these results indicate an evolutionary mechanism driven by indel accumulation in core Nup promoters. Compensation of such deleterious changes could lead to altered neuronal wiring, rapid fixation of adaptive traits and subsequently the rise of new species. Hence, the nuclear pore complex may act as a nexus for species-specific changes via nucleo-cytoplasmic transport regulated gene expression.

evolutionary biology↗

bioRxiv2022

sgRNA structural constraints and genetic limitations for efficient Cas9 genome editing to generate knock-outs

A single guide RNA (sgRNA) directs Cas9 nuclease for gene-specific scission of double-stranded DNA. High Cas9 activity is essential for efficient gene editing to generate gene deletions and gene replacements by homologous recombination. However, cleavage efficiency is below 50% for more than half of randomly selected sgRNA sequences in human cell culture screens or model organisms. We used in vitro assays to determine intrinsic molecular parameters for maximal sgRNA activity including correct folding of sgRNAs and Cas9 structural information. From comparison of over 10 data sets, we find major constraints in sgRNA design originating from defective secondary structure of the sgRNA, sequence context of the seed region, GC context and detrimental motifs, but we also find considerable variation among different prediction tools when applied to different data sets. To aid selection of efficient sgRNAs, we developed web-based PlatinumCRISPr, an sgRNA design tool to evaluate base-pairing and sequence composition parameters for optimal design of highly efficient sgRNAs for Cas9 genome editing named PlatinumCRISPr. We applied this tool to select sgRNAs to efficiently generate gene deletions in Drosophila Ythdc1 and Ythdf, that bind to N6 methylated adenosines (m6A) in mRNA. However, we discovered, that generating small deletions with sgRNAs and Cas9 leads to ectopic reinsertion of the deleted DNA fragment elsewhere in the genome. These insertions can be removed by standard genetic recombination and chromosome exchange. These new insights into sgRNA design and the mechanisms of CRISPR-Cas9 genome editing advances efficient use of this technique for safer applications in humans.

molecular biology↗

bioRxiv2021

Dynamically expressed ELAV is required for learning and memory in bees

Changes in gene expression are a hallmark of learning and memory consolidation. Little is known about how alternative mRNA processing, particularly abundant in neuron-specific genes, contributes to these processes. Prototype RNA binding proteins of the neuronally expressed ELAV/Hu family are candidates for roles in learning and memory, but their capacity to cross-regulate and take over each others functions complicate substantiation of such links. Therefore, we focused on honey bees, which have only a single elav family gene. We find that honey bee elav contains a microexon, which is evolutionary conserved between invertebrates and humans. RNAi knockdown of elav demonstrates that ELAV is required for learning and memory in bees. Indicative of a role as immediate early gene, ELAV is dynamically expressed with altered alternative splicing and subcellular localization in mushroom bodies, but not in other brain parts. Expression and alternative splicing of elav change during memory consolidation illustrating an alternative mRNA processing program as part of a local gene expression response underlying memory formation. Although the honey bee genome encodes only a single elav gene, functional diversification is achieved by alternative splicing.

molecular biology↗

bioRxiv2021

CMTr cap-adjacent 2`-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses

Cap-adjacent nucleotides of animal, protist and viral mRNAs can be dynamically O-methylated at the 2 position of the ribose (cOMe). The functions of cOMe in animals, however, remain unknown. Here we show that the two cap methyltransferases (CMTr1 and CMTr2) of Drosophila can methylate the ribose of the first nucleotide in mRNA. Double-mutant flies lack cOMe but are viable. Consistent with prominent neuronal expression, they have a reward learning defect that can be rescued by conditional expression in mushroom body neurons before training. Among CMTr targets are cell adhesion and signaling molecules relevant for learning and cOMe is required for local translation of mRNAs at synapses. Hence, our study reveals a mechanism to co-transcriptionally prime mRNAs by cOMe for localized protein synthesis at synapses.

molecular biology↗

bioRxiv2021

Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals

Neurons draw on alternative splicing for their increased transcriptomic complexity throughout animal phylogeny. To delve into the mechanisms controlling the assembly and evolution of this regulatory layer, we characterized the neuronal microexon program in Drosophila and compared it with that of mammals. We found that in Drosophila, this splicing program is restricted to neurons by the post-transcriptional processing of the enhancer of microexons (eMIC) domain in Srrm234 by Elav and Fne. eMIC deficiency or misexpression leads to widespread neurological alterations largely emerging from impaired neuronal activity, as revealed by a combination of neuronal imaging experiments and cell-type-specific rescues. These defects are associated with the genome-wide skipping of short neural exons, which are strongly enriched in ion channels. Remarkably, we found no overlap of eMIC-regulated exons between flies and mice, illustrating how ancient post-transcriptional programs can evolve independently in different phyla to impact distinct cellular modules while maintaining cell-type specificity.

molecular biology↗

bioRxiv2020

Mapping QTL associated with resistance to avian oncogenic Mareks Disease Virus (MDV) reveals major candidate genes and variants

Mareks Disease (MD) represents a significant global economic and animal welfare issue. Mareks Disease Virus (MDV) is a highly contagious oncogenic and highly immune-suppressive alpha-herpes virus, which infects chickens, causing neurological effects and tumour formation. Though partially controlled by vaccination, MD continues to have a profound impact on animal health and on the poultry industry. Genetic selection provides an alternative and complementary method to vaccination. However, even after years of study, the genetic mechanisms underlying resistance to MDV remain poorly understood. The MHC is known to play a role in disease resistance, along with a handful of other. In this study, one of the largest to date, we used a multi-facetted approach to identify QTL regions (QTLR) influencing resistance to MDV, including an F6 population from a full-sib advanced intercross line (FSIL) between two elite commercial layer lines differing in resistance to MDV, RNA-seq information from virus challenged chicks, and genome wide association study (GWAS) from multiple commercial lines. Candidate genomic elements residing in the QTLR were further tested for association with offspring mortality in the face of MDV challenge in 8 pure lines of elite egg-layer birds. Thirty-eight QTLR were found on 19 chicken chromosomes. Candidate genes, miRNAs, lncRNAs and potentially functional mutations were identified in these regions. Association tests were carried out in 26 of the QTLR, using 8 pure lines of elite egg-layer birds. Numerous candidate genomic elements were strongly associated with MD resistance. Genomic regions significantly associated with resistance to MDV were mapped, and candidate genes identified. Various QTLR elements were shown to have strong genetic association with resistance. These results provide a large number of significant targets for mitigating the effects of MDV infection on both poultry health and the economy - whether by means of selective breeding, improved vaccine design or gene-editing technologies. Author summaryMareks Disease has a huge impact on the global poultry industry in terms of both animal welfare and economic cost. For many years, researchers have sought to identify the genes underlying resistance to Mareks Disease Virus (MDV). However, this is a complex trait with each genetic locus having a small effect, so identifying causal genes and variants is no easy task. To date, it is known that the MHC confers differing susceptibility/resistance. A few other non-MHC genes have also been implicated in disease resistance, although based on experimental inbred lines and not representing real world commercial poultry. Using an F6 intercross population of birds with differences in MDV survival, we have identified many regions of the genome involved in resistance and highlighted candidate genes, miRNAs and lncRNA. Access to DNA from phenotyped birds spanning 15 generations of 8 elite commercial lines has provided a unique opportunity for us to show genetic association of markers in these transcripts with MDV survival. This genetic study, the largest to date, provides novel targets for mitigation of Mareks Disease within the poultry industry. This could be through selective breeding strategies, improved vaccine design or future gene editing technologies.

genomics↗