Biology subjects

Mulley, J.

Publications and source records attributed to Mulley, J..

4 recordsLinked to original sources

bioRxiv2024

Large-scale mouse mutagenesis identifies novel genes affecting vertebral development.

We analyzed the International Mouse Phenotyping Consortium (IMPC) release 19 set of 8,539 phenotyped whole-gene knockouts to identify 204 genes that alter vertebral development. These genes are broadly grouped into six categories based on their phenotype: "vertebral number" (22 genes); "vertebral processes" (35 genes); "spine shape" (16 genes); "tail morphology" (73 genes); "vertebral form" (62 genes); and "somitogenesis" (24 genes), with minimal overlap between groups. Gene expression analysis of somite trios across six developmental stages show that 182 of these genes are expressed in somites, and 60% of them show variable expression during somite maturation. A further 54% show expression changes between developmental stages. Fourteen of the 204 genes affecting vertebral development have a vertebral phenotype as their only phenotype, and for 34 genes vertebral phenotypes represent [≥]50% of their total phenotypes. We find no evidence for a previous association of the majority of these genes with vertebral defects, and have therefore identified an extensive set of novel candidate genes for association with vertebral malformations in humans, including vertebral fusions, numerical variation, and scoliosis.

developmental biology↗

bioRxiv2024

The sensory shark: high-quality phenotypic, genomic and transcriptomic data for the small spotted catshark Scyliorhinus canicula reveal the molecular bases of sensory organ evolution in jawed vertebrates

Cartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

evolutionary biology↗

bioRxiv2022

The origin of a new chromosome in gerbils

Chromosome-scale genome assemblies based on ultra-long read sequencing technologies are able to illuminate previously intractable aspects of genome biology such as fine-scale centromere structure and large-scale variation in genome features such as heterochromatin, GC content, recombination rate, and gene content. We present here a new chromosome-scale genome of the Mongolian gerbil (Meriones unguiculatus) which includes the complete sequence of all centromeres. Gerbil centromeres are composed of four different repeats of length 6pb, 37bp, 127bp, or 1747bp which occur in simple alternating arrays and span 1-6Mb. Gerbil genomes have both an extensive set of GC-rich genes and chromosomes strikingly enriched for constitutive heterochromatin. We sought to determine if there was a link between these two phenomena and found that the two heterochromatic chromosomes of the Mongolian gerbil have distinct underpinnings: Chromosome 5 has a large block of intra-arm heterochromatin as the result of a massive expansion of centromeric repeats, while chromosome 13 is comprised of extremely large (>150kb) repeated sequences. In addition to characterizing centromeres, our results demonstrate the importance of including karyotypic features such as chromosome number and the locations of centromeres in the interpretation of genome sequence data, and highlight novel patterns involved in the evolution of chromosomes.

genomics↗

bioRxiv2019

Shed skin as a source of DNA for genotyping-by-sequencing (GBS) in reptiles

Over a fifth of reptile species are classified as Threatened and conservation efforts, especially those aimed at recovery of isolated or fragmented populations, will require genetic and genomic data and resources. Shed skins of snakes and other reptiles contain DNA, are a safe and ethical way of non-invasively sampling large numbers of individuals, and provide a simple mechanism by which to involve the public in scientific research. Here we test whether the DNA in dried shed skin is suitable for reduced representation sequencing approaches, specifically genotyping-by-sequencing (GBS). Shed skin-derived libraries resulted in fewer sequenced reads than those from snap-frozen muscle samples, and contained slightly fewer variants (70,685 SNPs versus 97,724), but this issue can easily be rectified with deeper sequencing of shed skin-derived libraries. Skin-derived libraries also have a very slight (but significantly different) profile of transitions and transversions, most likely as a result of DNA damage, but the impact of this is minimal given the large number of single nucleotide polymorphisms (SNPs) involved. SNP density tends to scale with chromosome length, and microchromosomes have a significantly higher SNP density than macrochromosomes, most likely because of their higher GC content. Overall, shed skin provides DNA of sufficient quality and quantity for the identification of large number of SNPs, but requires greater sequencing depth, and consideration of the GC richness of microchromosomes when selecting restriction enzymes.

genetics↗