Genes

BackgroundAlpha satellites, a superfamily of AT-rich tandem repeats, are the primary DNA component of centromeres in Platyrrhini and Catarrhini. Analyses of the human genome suggest that centromeres behave like biological ridges, with new alpha satellite families expanding at the centromere core, splitting and displacing older ones towards the pericentromeres. The Cercopithecini tribe, which displays an unusual chromosomal evolution involving multiple chromosomal fissions and centromere formations, represents a promising model to enhance our understanding of alpha satellite DNA evolutionary history. We previously applied targeted sequencing to centromere DNA from two distant species drawn from the Cercopithecini terrestrial and arboreal lineages, and characterized six alpha satellite families exhibiting varying mean sequence identities. MethodsCombining classical and molecular cytogenetics, we mapped the chromosomal distribution of these alpha satellite families across 13 Cercopithecini, one Papionini, and one Colobinae species. A nuclear marker-based phylogeny provided an evolutionary framework for interpretation. ResultsOur phylogeny identifies the terrestrial and arboreal lineages, and a newly designated swamp clade. We observed significant interspecies variations in alpha satellite patterns, including differences in presence/absence and distinct chromosomal distribution patterns (centromeric, pericentromeric, or subtelomeric). Families previously described as heterogeneous (83-87% mean sequence identity) exhibit a centromeric position in the swamp lineage, which is characterized by conserved karyotypes. In contrast, these families show a pericentromeric distribution in the terrestrial and arboreal lineages, replaced at the centromere core by more homogeneous families (95-98% mean sequence identity). In the arboreal clade, which is characterized by highly fissioned karyotypes, putative evolutionary new centromeres show a unique co-occurrence of highly homogeneous and heterogeneous families. Conclusion & ImplicationsWe propose a comprehensive evolutionary scenario for alpha satellite DNA in Cercopithecini, where younger families arise at the centromere core, shift toward the pericentromeres as they age, and eventually face extinction. Our study suggests that alpha satellite DNA and chromosomes evolve in an interdependent manner, with satellite diversification and displacement occurring in parallel with chromosome fissions and centromere repositioning. This comparative cytogenomic approach provides both support for the human-based evolutionary model for alpha satellite DNA and novel temporal insights into its diversification dynamics. Beyond evolutionary genomics, our findings highlight the potential of alpha satellite DNA to complement systematic studies in deciphering complex primate evolutionary histories.

The measurement of inbreeding has gained significance across diverse fields, including population and conservation genetics, agricultural genetics, breeding programs for animals and plants, and wildlife management. This is due to the fact that inbreeding leads to increased homozygosity and results in lower genetic diversity, rendering populations more vulnerable to environmental changes, diseases, and other stressors. High or mid-coverage whole genome sequencing (WGS) has been widely used for inbreeding estimation, but it is resource-intensive. We aimed to investigate the use of ultra low-coverage whole genome sequencing (ulcWGS) as a cost-effective alternative for inbreeding analysis. Domestic dogs were used for our study as their extensive breeding histories lead to populations with a wide range of inbreeding levels. We constructed a multi-breed reference panel from high-coverage WGS samples. Inbreeding in independent ulcWGS samples was then estimated using runs of homozygosity (RoH) and inbreeding coefficients (F). We modeled the relationship between these measures and sequencing depth using nonlinear regression, to generate inbreeding estimates relative to sequencing depth. Resulting relative RoH and F measurements were significantly correlated, with purebred dogs exhibiting more runs of homozygosity and higher inbreeding coefficients compared to mixed-breed dogs. Our findings demonstrate that ulcWGS can provide reliable and economical estimations of inbreeding, expanding accessibility to genetic monitoring.

BackgroundMaize knobs are regions of constitutive heterochromatin that are readily identified in both meiotic and somatic chromosomes. These structures have been characterized as stable throughout the cell cycle, exhibiting late replication during the S-phase, and are composed of two specific families of highly repetitive DNA sequences: K180 and TR-1. Although widely used as cytogenetic markers due to their variability in number and chromosomal position across inbred lines, hybrids, and landraces, little is known about their chromatin structure and dynamics. In this study, we analyzed chromatin accessibility of knobs using DNS-seq data across four maize tissues representing distinct developmental stages. ResultsOur results reveal that K180 knobs exhibit tissue-specific variation in chromatin accessibility, transitioning between open and closed states during development. In contrast, the TR-1 knob of chromosome 4 remained consistently inaccessible across all tissues analyzed. A knob composed of both K180, and TR-1 further supported this observation, with only the K180 region showing dynamic accessibility. To validate these findings, we also analyzed other repetitive regions such as centromeres, which showed a uniformly closed chromatin structure similar to TR-1. These results suggest a unique developmental modulation of chromatin accessibility associated with K180 repeats. While the chromatin accessibility of knobs does not reach the levels observed at Transcription Start Sites (TSS), the comparison among different classes of repetitive DNA within maize constitutive heterochromatin provides compelling evidence for sequence-specific and tissue-specific chromatin dynamics. ConclusionsOur findings uncover a previously unrecognized property of maize knobs and establish a reference for future studies on chromatin organization and epigenetic regulation of repetitive DNA in plant genomes.

Proteins and non-coding RNAs are functional products of the genome that are central for crucial cellular processes. With recent technological advances, researchers can sequence genomes in the thousands and probe numerous genomic activities of many species and conditions. Such studies have identified thousands of potential proteins, RNAs and associated activities. However there are conflicting interpretations of the results and therefore which regions of the genome are "functional". Here we investigate the relative strengths of associations between coding and non-coding gene functionality and genomic features, by comparing reliably annotated functional genes to non-genic regions of the genome. We find that the strongest and most consistent association between functional genes and genomic features are transcriptional activity and evolutionary conservation. We also evaluated sequence-based statistics, genomic repeats, epigenetic and population variation data. Other features strongly associated with function include histone marks, chromatin accessibility, genomic copy-number, and sequence alignment statistics such as coding potential and covariation. We also identify potential issues with SNP annotations in short non-coding RNAs, as some highly conserved ncRNAs have significantly higher than expected SNP densities. Our results demonstrate the importance of evolutionary conservation and transcription activity for indicating protein-coding and non-coding gene function. Both should be taken into consideration when differentiating between functional sequences and biological or experimental noise.

BackgroundTransposable elements (TEs) are repetitive genetic elements that can jump to new loci causing genome expansions, structural rearrangements, and can, ultimately, propel the evolution of genomes. Despite their significance, the role of TEs in the evolution of genomes and phylogenetic groups remains largely understudied in early diverging lineages. Further, the extent to which TE content varies across species is still an open question. Medusozoa, a group within Cnidaria encompassing jellyfish and hydroids, exhibits an exceptional diversity of life history strategies, body plans, and physiological capabilities. These characteristics, along with its early-diverging phylogenetic position, establish Medusozoa as an ideal system for investigating the composition and evolutionary history of TEs within the group. ResultsWe generated a custom repeat library built from annotations of 25 Medusozoan genomes and used it to characterize TEs, aiming to identify lineage-specific TE content and activity that may correlate with the diversity observed within the group. We found that repetitive element percentage and genome size varied considerably, with Hydrozoa exhibiting the most variation among classes in both respects. DNA transposons were the most prevalent TE classification in all but two genomes, averaging 28% of all genomes. Intra-genus comparisons revealed a surprising degree of differences in TE content. In the genus Aurelia, the expansion of a single DNA transposon superfamily accounted for much of the difference in repetitive element percentage between two species, whereas in the genus Turritopsis, a similar divergence resulted from the proliferation of multiple superfamilies. Interestingly, most genomes showed evidence of recent TE expansions, suggesting ongoing activity in many medusozoan species. ConclusionWe present the first comparative analysis of TEs across all medusozoan classes. Our results reveal class-specific TE dynamics and highlight cases of TE proliferations as lineages diverge. This research provides data on TE activity and diversity that can be used as a resource for future study and fills important gaps in our understanding of TEs in early diverging animal lineages.

BackgroundPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder and a leading cause of female infertility, with complex genetic, metabolic, and hormonal etiologies. Long non-coding RNAs (lncRNAs) have emerged as important regulators of diverse biological processes, yet their roles in PCOS remain underexplored. Here, we identified and characterized PCOS differentially expressed gene-associated lncRNAs (PDEGAL) with an integrative approach combining expression data, genetic association, and evolutionary analysis. MethodsThirty-three PCOS-associated protein-coding genes were obtained from our prior study, and all their nearby and overlapping lncRNAs were annotated. These candidates were analyzed using UCSC Genome Browser-mapped annotations and datasets, including NCBI RefSeq, GENCODE, GTEx, GWAS SNPs, and conservation, as well as the FANTOM5 cap analysis of gene expression (CAGE) promoter data, to assess their expression, regulatory potential, genetic variant overlaps, and evolutionary conservation. ResultsTwenty-three PDEGALs (18 antisense to, and 5 sharing bidirectional promoters with, known PCOS-associated protein-coding genes) were identified. 17 PDEGALs contained GWAS SNPs with statistically significant disease associations, 9 of which were associated with PCOS-related traits. 5 PDEGALs demonstrated expression in the KGN granulosa cell model of PCOS. Key gene structure element (KGSE) analysis revealed that most PDEGALs are primate-specific. Integrating four criteria--GTEx expression, GWAS SNPs, FANTOM promoterome, and KGSE conservation--highlighted HELLPAR as the only lncRNA fulfilling all four, while five others--PGR-AS1, MTOR-AS1, ENSG00000265179, ENSG00000256218, and LOC105377276--fulfilled three of the four criteria. ConclusionsWe have systematically identified candidate PCOS regulatory lncRNAs with convergent genetic, expression, and evolutionary evidence. These results provide a framework for functional validation and highlight lncRNAs as potential biomarkers and therapeutic targets in PCOS that function by regulating their nearby and overlapping protein-coding genes.

AimThe commercial interest of grapevines (Vitis vinifera L.) has prompted numerous studies on their origin and genetic resources in the context of global change. However, genomic-scale information on diversity patterns and genetic structure in southwestern Europe remains scarce. This study infers the genetic structure, gene flow events between genetic groups, and genetic refugia of Vitis vinifera ssp. sylvestris in the Iberian Peninsula. LocationThe Iberian Peninsula. TaxonThe wild grapevine, Vitis vinifera L. ssp. sylvestris MethodsWe reanalyzed a set of 137 complete genomes of V. vinifera ssp. sylvestris. After variant calling, validation and annotation, we obtained a high-quality SNP dataset. Using these markers, we performed phylogenetic and population structure analyses to determine the number and spatial distribution of genetic groups and their contact zones. Next, we inferred the timing and directionality of gene flow events between groups. Finally, heterozygosity and allele rarity were estimated to identify populations with high conservation value. ResultsWe detected three major ancestral populations and four putative genetic refugia in the south of the Iberian Peninsula. Demographic analyses indicate sustained gene flow between [~]21,000 and [~]7,000 years ago from a North African ancestral group into Iberian wild populations in the south. Heterozygosity and allele rarity analyses identified populations of high conservation value in a variety of areas within the Iberian Peninsula. Main ConclusionsWe identify the biogeographical factors behind the long-known singularity of wild Iberian grapevines. The southern Iberian Peninsula is a hotspot of genetic diversity for wild grapevines, hosting three ancestral populations and multiple contact zones that acted as micro-refugia. The current genetic variability of Iberian wild grapevines is best explained by natural, climate-driven gene flow between African lineages with Middle Eastern origin and Iberian groups. These contacts were favored by climatic conditions during the late Pleistocene ([~]21,000 years) and early Holocene ([~]8,300 years). Our results dismiss a significant anthropogenic influence during Neolithic domestication for explaining the genetic composition of Iberian wild grapevine genotypes.

BackgroundAlthough strict maternal transmission of mitochondria is a general feature of animals and humans for ensuring homogeneity in mitochondrial DNA (mtDNA) across generations, exceptions were reported in the recent past. For example, some extremely rare but spectacular cases of heteroplasmy and paternal transmission in humans have questioned the universal evolutionary principle. Hence, as an alternative, the Mega-NUMT concept was coined to explain this discovery and was thereafter partly proven to exist. This concept expands on the quite common transfer of mtDNA fragments to the nucleus (NUMTs) by considering the existence of multicopy mitochondrial nuclear insertions. Mega-NUMT reports are currently restricted to a few cases in animals, including humans. However, even in humans, their detailed genomic organization, natural prevalence, and potential biological functions remain unclear. Methodology/Principal FindingsHere, we discovered that up to 60 full-sized mitochondrial genomes are integrated into the nuclear genome of the neotropical fruit fly Drosophila paulistorum using long-read sequencing and confirmed their presence by in situ hybridization. The copies are organized in one cluster on chromosome 3, which we, due to its similarity with the Mega-NUMT concept, designated the "Dpau Mega-NUMT". Contrary to the rarity in humans, this Mega-NUMT is found at high prevalence (40%) in both long-term laboratory lines and natural D. paulistorum populations of different semispecies. Additionally, the mitochondrial copies in the Mega-NUMT cluster are phylogenetically separated from the current mitotypes of D. paulistorum. Together, these observations suggest long-term maintenance of the Mega-NUMT in nature. Hence, we propose that the Dpau Mega-NUMT may have been transferred to the nuclear genome before D. paulistorum semispecies radiation and maintained at relatively high prevalence in nature by balancing selection due to yet undetermined functions. Conclusions/SignificanceTo our knowledge, this is the first verified existence and detailed dissection of a Mega-NUMT outside cats and humans. We show that Mega-NUMTs can be persistent in nature, even at high prevalence, potentially due to balancing selection. Our findings strengthen the importance of high-quality long-read sequencing technologies for deciphering complex repeat-rich genomic regions to deepen our understanding of the dynamics of genome evolution within genomic "dark matter".

PurposeTo determine whether circadian timing defines critical molecular windows in myopia development and to assess the transferability of circadian gene programs across ocular tissues, disease stages, and species. MethodsPublicly available retinal and choroidal RNA-seq datasets from chick models of form-deprivation myopia were analyzed using unsupervised transcriptomic profiling and multistage machine-learning classification. Circadian windows were defined based on Zeitgeber time, and samples were grouped accordingly for downstream analyses. Classification model robustness was evaluated through cross-tissue and cross-stage validation and further assessed using external validation in an independent dataset. Functional translation to humans was examined using ortholog-based Gene Ontology enrichment analysis to identify conserved biological processes and higher-order regulatory pathways. ResultsA circadian critical window at ZT8-ZT12 exhibited the strongest transcriptional divergence during both myopia onset and progression. Gene signatures derived from this window generalized across retina and choroid and remained predictive across disease stages, supporting coordinated molecular regulation between ocular tissues. External validation confirmed the reproducibility of these signatures despite differences in experimental design and gene coverage. Functional mapping revealed that conserved molecular components in chicks are reorganized into more complex neuroendocrine and regulatory networks in humans, indicating cross-species conservation with increased functional complexity. ConclusionsCircadian timing strongly shapes myopia-related gene expression and underlies coordinated retina-choroid signaling. These findings highlight circadian biology as a key factor of refractive development and suggest that time-dependent mechanisms may influence myopia susceptibility, progression, and response to treatment.

Short Interrupted Repeats Cassettes (SIRC) are recently discovered eukaryotic DNA elements possessing many traits of satellite DNA and mobile genetic elements, and consisted of short direct repeats interspersed with diverse spacer sequences. The SIRC ensemble of individual species is highly heterogenous and cannot be studied using alignment methods. It was found that number of similar SIRC sequences in a given pair of species is in general correlated with their taxonomic distance, and, at the same time, closely related species can possess very diverged SIRC ensembles, which makes SIRC evolutionary pattern closer to mobile genetic element type. The SIRC sequences make up clusters with comparable sequence patterns, that are likely to demonstrate doublet evolutionary model which strongly supports that the SIRC structure is supported by the evolutionary selection. Several SIRC sequences of Arabidopsis were found to be of ancient origin with traceable evolution history as far as to the moss clade. We carried out unbiased detection of SIRC ensembles in 10 plant genomes and found that, despite very high intraspecies heterogeneity, SIRC sets possess strong interspecies phylogenetic signal. Key messageShort Interrupted Repeats Cassettes are elements of ancient origin, and could potentially be used to trace organism history, and to facilitate syntheny and Hi-C analysis.

We present a novel integrative analysis of transposable elements (TEs) in 4 single cell RNA-seq (scRNA-seq) datasets of postmortem substantia nigra pars compacta samples of Parkinson Disease (PD) patients matched healthy controls, with the objective of building a cell-type specific trustworthy atlas of TEs that may clarify the role of TEs in sex differences in PD. We have used the soloTE tool to evaluate the TEs expression changes across all snRNA-seq studies identified in our previous systematic review, and then integrated the results using meta-analysis techniques. Finally, we evaluated the possible associations between TEs and protein coding genes by integrating our previous results in this matter with the information of TEs obtained, in order to propose the possible action mechanism by which some of the TEs contribute to PD.

Introduction: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital malformation with complex etiology involving both genetic and environmental factors. Epigenetic mechanisms may mediate environmental contributions, but separating genetic from environmental effects remains challenging. Methods: We present an epigenome-wide association study with 32 monozygotic and 22 dizygotic twin pairs discordant for NSCL/P on blood and saliva samples. Differential methylation analysis was conducted using linear models to identify CpG sites showing significant methylation differences between affected and unaffected twins followed by functional annotation and pathway enrichment analysis. Results: The top-ranked finding is a differentially methylated region comprising two CpG sites at the CYP26A1 locus, cg12110262 (P = 3.21x10-7) and cg15055355 (P = 1.39x10-3). CYP26A1 is essential for retinoic acid catabolism and craniofacial patterning. The chromatin regulator ANKRD11, which causes KBG syndrome featuring cleft palate was the second best hit. Differentially methylated CpG sites showed significant enrichment in craniofacial enhancers and overlap with multiple GWAS-validated cleft genes including VAX1, PVRL1, SMAD3, and PRDM16. Conclusions: Our findings implicate retinoic acid signaling and chromatin regulation in NSCL/P etiology and demonstrate the value of discordant twin designs for distinguishing environmental from genetic epigenetic contributions to complex malformations.

The worlds largest and rarest eagle, the Philippine Eagle (Pithecophaga jefferyi), also known as the monkey-eating eagle, is the national bird of the Philippines. This raptor species is endemic to the Philippine archipelago, with populations on the islands of Luzon, Leyte, Samar, and Mindanao. It is critically endangered, with an average estimated population of 392 potentially breeding pairs or 784 mature individuals. In this paper, we describe a reference genome of the Philippine Eagle (Pithecophaga jefferyi) from a female juvenile from the province of Nueva Ecija on the island of Luzon. We generated a de novo genome assembly with high contiguity and completeness, comprising 178 contigs totaling 1.345 Gbp. The genome was sequenced at a coverage of 75.2x, and Benchmarking Universal Single-Copy Orthologs (BUSCO)/Compleasm analysis yielded a BUSCO score of 99.92% (aves_odb12), corresponding to 99.7% single-copy, 0.21% duplicated, and 0.08% fragmented genes. A consensus mitogenome sequence of 19,377 bp was also generated. The genome assembly included 23,847 putative genes, and our annotation estimated that 15.78% of the genome consisted of repetitive elements. Genome heterozygosity (H) was estimated to be 0.020%, in comparison to other birds with genome heterozygosity values ranging from 0.0103% to 0.923%. Whole-genome comparisons with publicly available genomes suggest that the Philippine eagle belongs to the snake-eagle subfamily (Circaetinae) rather than the harpy-eagle subfamily (Harpiinae). Pairwise sequentially Markovian coalescent (PSMC) analysis suggests that the effective population size was around 4,000 individuals from about 100 KYA to about 1 KYA. Finally, we constructed a minimum spanning network, which revealed that our mitogenome from the northern island of Luzon occupies a peripheral position, separated from the dominant haplotype cluster found in the southern island of Mindanao by multiple mutational steps, indicating substantial mitochondrial divergence.

Identifying loci in the genome that allow a population to respond to selection pressure is essential to understand evolution and improve crops. Temporally consecutive generations under selection offer the opportunity to identify signatures of selection. Maize, as one of the most important crops worldwide is rich in genetic diversity and a model for breeding advances. Therefore, it is an ideal system to study genetic changes in response to selection. Here, we study the genetic changes in two replicates of a selection experiment in a European maize landrace, which showed rapid trait improvement over three cycles of selection. We identified an increase in genetic divergence across successive doubled-haploid populations derived from each selection cycle, consistent with the effect of strong directional selection. The genetic divergence observed between the replicates was greater than that between generations. In addition to the genome-wide signal, we identified multiple candidate loci under selection through temporal FST outlier analysis comparing the original landrace population to subsequent cycles. These loci showed a significant overlap with genomic regions, controlling intentionally selected traits and other traits. The significant overlap of selected loci between the two replicates shows the importance of major loci in response to directional selection, while the large number of non-overlapping loci demonstrates the polygenic response. Our work shows that the temporal dimension in plant breeding time-series enables the identification of candidate loci under selection and the genome-wide dynamics of change in response to selection.

Genomic imprinting is a rare epigenetic phenomenon in plants and animals, defined by parent-of-origin specific gene expression. Its molecular mechanisms and evolutionary significance remain incompletely understood. In this study, we investigated whether genomic imprinting occurs in Scots pine and, by extension, in other conifers to gain insight into the evolutionary origins of imprinting. We performed reciprocal crosses to assess imprinting in seed embryos and applied a unique approach that used exome-capture data from the haploid, maternally inherited megagametophyte tissue to identify maternal alleles, thereby allowing us to infer paternal alleles in the embryos of the same seeds. Our findings show that maternally inherited haploid megagametophyte tissue offers an effective strategy for resolving parental alleles in offspring while simultaneously removing extensive paralogous variation from the dataset. This framework is broadly applicable to other conifer species and to taxa that possess comparable maternally derived haploid tissues. No evidence of genomic imprinting was detected. Although the limited overlap between the exome-capture and RNA-sequencing datasets and the stringent paralog filtering reduced the amount of analyzable data considerably, the absence of detectable imprinting may also reflect genuinely weak or absent imprinting signals in conifers. We identified several limitations in this preliminary study and outline recommendations for future work to overcome them, and additional research will be necessary to determine whether genomic imprinting occurs in conifers

Background As part of Singapore's effort towards precision medicine tailored to Asian diversity, we describe the implementation of a nationwide reproductive carrier screening program. Using a customised 112-gene panel, incorporating population-specific recessive genetic diseases, we outline the overall program design, and initial efforts of community and stakeholder engagement, to inform culturally appropriate implementation. Methods Participants receive culturally tailored online education regarding our reproductive screening program and are provided results with genetic counselling and reproductive options. Community and stakeholder perspectives were assessed through questionnaires and consultations with religious leaders. Results Recruitment is nation-wide, and since initiation of our pilot phase in September 2024, 1,619 couples have registered interest, with 60% uptake of those deemed eligible. Among the 456 couples that have received results to date, four couples (0.9%) were identified to be at increased risk. Community questionnaire responses (n=1002), involving couples who participated in the program as well as the general public, indicated interest is high (59%) across the cohort but awareness, intent to participate and implications for reproductive options differed by sociodemographic factors such as ancestry and religion. Healthcare professional respondents (n=113) acknowledged carrier screening will be routine in medical care, but report limited confidence and resources. Engagement with religious leaders indicated support for the program. Conclusion These early program outcomes and community engagement are guiding the implementation of expanding population-based carrier screening in Singapore, contingent on addressing practical challenges through equitable outreach and professional training.

All cells of a multicellular organism usually share an identical genome, faithfully transmitted through successive divisions. Yet, a number of animal species deviate from this dogma, as parts of their DNA are systematically eliminated in all their somatic nuclei, in a process called Programmed DNA Elimination (PDE). PDE leads to the unexpected reorganisation of the genome at every generation in all somatic cells but its molecular mechanism, evolutionary origins, and functional significance remain unknown. This lack of understanding partially stems from limitations in genetically tractable model species. PDE can target an entire chromosome, or involve chromosome fragmentation followed by selective fragment retention and elimination, raising further questions on genome stability, genome integrity and mechanisms of DNA repair. PDE by chromosome fragmentation has been described in parasitic nematodes in the family Ascarididae, copepods in the genus Cyclops and unicellular ciliates. More recently, PDE has been discovered in three non-parasitic, lab-tractable nematode species from the Rhabditidae family, opening new perspectives. In this study, we used cytological approaches to screen 25 new Rhabditidae species for PDE. We found evidence of PDE in 17 species. Our work reveals that PDE is present in 12 out of 17 tested genera, demonstrating its widespread presence in Rhabditidae nematodes, with the notable exception of C. elegans. Genetic tools have already been established for some species. This work provides a collection of lab-tractable species that can be used to test many aspects of somatic Programmed DNA Elimination by chromosome fragmentation in animals.

Objective The decline of the perinatal demise rate is slowing and demises are often unexplained. Significant research has been done regarding diagnostic yield and genetic causes of demise, but little is known about how Geneticist involvement impacts outcomes. The goal of the study was to evaluate post-mortem genetic testing practices and effects of the geneticists involvement. Methods Retrospective data from 111 perinatal demise cases was examined, including rates of prenatal genetic counseling, post-delivery genetics consult, genetic testing, and autopsy investigation. Results In this cohort 54% received genetic testing and 25% received a genetics consult. When compared to those without, cases with genetic specialist involvement were associated with significant increases in testing uptake (p=0.007), diagnostic yield (p<0.001), and patient education (p<0.001). Second trimester stillbirths and those with fewer ultrasound (US) abnormalities were less likely to receive genetic testing (both p values <0.001) and consults (p<0.001, p=0.020). Conclusion Though it was not possible to avoid ascertainment bias, this data demonstrates that geneticist involvement correlates with a higher rate of testing, greater diagnostic yield, and more thorough counseling. These findings underscore the importance of integrating genetics providers into perinatal postmortem healthcare teams.

In our society, ageing, longevity, and neurodegenerative diseases are major concerns of public health. Recently, in Drosophila, we have identified a new cluster of three snoRNAs, including jouvence, and showed that each of them affect longevity and neurodegeneration. As these snoRNAs are required in the epithelium of the gut, these results point-out a causal relationship between the epithelium of the gut and the neurodegenerative lesions through the metabolic parameters, indicating a gut-brain axis. Here, we demonstrate that each snoRNA pseudouridylates a specific site on ribosomal-RNA, which consequently affects the amount of ribosomes as well as the translational efficacy. Moreover, using TRAP experiment assay, we also show that these lacks of pseudouridylations modify the translation of specific genes involved in lipid metabolism. Consequently, these lead to a chronic deregulation of trigycerides and sterols levels, whose correlate to an increase of neurogenerative lesions in old flies, as well as to a modification of longevity.

High and low tides occur twice a day (every [~]12.4 hours), with the largest tidal ranges during spring tides around new and full moons (every [~]14.765 days). While these lunar cycles are known to influence many animal phenotypes, particularly the reproduction of coastal animals, the genetic basis of lunar-related rhythms remains unclear. Since phenotypic variation is a valuable resource for elucidating such mechanisms, we examined geographic variation in the lunar-regulated mass spawning of the grass puffer (Takifugu alboplumbeus) along the Japanese coast. We found that western populations spawn during the first half of the spring tides, whereas eastern populations spawn during the second half. Furthermore, although spawning typically occurs a few hours before high tide, this timing is restricted to a specific time window that is earlier in the western populations than in the eastern ones. Behavioral analysis of larvae also revealed a shorter free-running circadian period ({tau}) in the western population than in the eastern ones. As differences in {tau} affect individual variation in the timing of physiological functions and behaviors, we hypothesized that differences in {tau} could account for the different time windows and consequently the observed difference in spawning days. Population genomics analysis identified proline-rich transmembrane protein 1-like (prrt1l) as a candidate gene. Expression of prrt1l was observed in the circadian pacemaker suprachiasmatic nucleus, and triple CRISPR F0 knockout of prrt1l shortened the free-running period in larvae. These findings suggest a potential mechanism underlying the geographic variation in lunar-synchronized spawning behavior. HighlightsO_LIThe geographic variation exists in the lunar-regulated spawning of the grass puffer, with differences in spawning dates and times between western and eastern Japan. C_LIO_LIThe free-running period of western populations is shorter than that of eastern populations, which is consistent with their earlier spawning timing. C_LIO_LIPopulation genomics analysis identified prrt1l as a candidate gene harboring population-specific missense mutations, the knockout of which shortens the free-running period. C_LI