Genes

Complex rearrangements are one of the rarest types of structural variants (SVs) and can be divided into two categories: complex chromosomal rearrangements (CCRs) and complex genomic rearrangements (CGRs). CCRs include structural rearrangements that present at least three breakpoints and show exchange of genetic material between more than two chromosomes and CGRs are rearrangements that present more than one junction and/or more than one SV in cis. They are usually formed by one of the chromoanagenesis mechanisms, where a massive disruptive cellular event leads to multiple structural rearrangements. Classical cytogenomic techniques have been commonly applied for their characterization, but methodologies that involve longer DNA molecules, namely optical genome mapping (OGM) and long-read genome sequencing (lrGS), present a considerably higher SV detection resolution, revealing more details about the rearrangements, including precise breakpoint location. Here, we describe six patients with complex rearrangements investigated through a combination of different techniques: karyotyping, chromosomal microarray, and OGM were performed to characterize the rearrangements. Subsequently, lrGS was used to further resolve the alterations, refine their breakpoints' location, and sequence their junction points. Three patients presented CCRs involving three, four, and six chromosomes, while three exhibited CGRs involving one different chromosome each, providing a variety of complex SVs to show the importance of each technique and their combination in rearrangement resolution. In total, the complex rearrangements presented 127 breakpoints, 66 junction points and involved 14 of the 24 chromosomes. Higher-resolution techniques revealed additional complexity in all cases. Despite the advances provided by OGM and lrGS, conventional karyotyping remained indispensable for complete rearrangement resolution. In two patients, the findings supported a novel mechanism combining features of the different chromoanagenesis processes. Furthermore, evidence of inherited alterations was identified, and the comprehensive characterization of the rearrangements enabled more accurate genotype-phenotype correlations. Our findings indicate that an integrated approach combining karyotyping, OGM, and lrGS can completely resolve SVs, including complex rearrangements.

Background: Uveal melanoma (UM) and cutaneous melanoma (CM) both originate from the same cell line. This proposes the possibility of a shared mechanism between entities, requiring explicit investigation. Methods: Data from GWAS Catalog and DisGeNET were used to identify shared variation-disease associations (VDAs) between UM and CM. The results were validated using the Ensembl database. In the next step, the STRING database was used to identify the protein-protein interaction. Results: Subsequently, 109 unique VDAs were identified for UM and 880 for CM. However, only 2 VDAs were found to be shared among UM and CM in different ethnic groups. These shared VDAs were rs12203592 of the IRF4 gene, rs12913832 of the HECT and RLD domain-containing E3 ubiquitin protein ligase 2 (HERC2) gene. Notably, PPI network assessment through STRING showcased that OCA2 and IRF4 directly interacted with HERC2. Conclusion: While HERC2 acts as a poor prognostic factor in uveal melanoma, IRF4 status is a key prognostic indicator in both UM and CM. Identifying IRF4 allele contributions enables a better understanding of melanoma pathogenesis and fosters the development of disease-specific approaches.

Gene model for the ortholog of Insulin-like peptide 3 (Ilp3) in the D. pseudoobscura Apr. 2013 (BCM-HGSC Dpse_3.0/DpseGB3) Genome Assembly (GenBank Accession: GCA_000001765.2) of Drosophila pseudoobscura. This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

Gene model for the ortholog of Density regulated protein (DENR) in the Apr. 2013 (BCM-HGSC Dpse_3.0/DpseGB3) Genome Assembly (GenBank Accession: GCA_000001765.2) of Drosophila pseudoobscura. This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

Background: Epigenetics, the study of reversible changes in gene expression without altering the underlying DNA sequence, is increasingly applied in medical, commercial, and policy contexts. Yet, little is known about how this emerging science is communicated to the public. The purpose of this study was to examine communication strategies, sources, and modalities in epigenetic-related videos on YouTube- the most accessed platform for informal science education. Methods: We conducted a mixed-methods content analysis of 294 YouTube videos on epigenetics by conducting a keyword-based search on October 17, 2023. Video transcripts and meta-data were coded using a codebook developed both deductively and inductively. Qualitative analysis examined how communication strategies were used within videos and identified emergent themes (RQ1). Quantitative analyses examined the frequency of video and channel characteristics (RQ2), and presentation modalities (RQ3). Results: Findings reveal poor alignment with science communication best practices (RQ1): over 92% of videos failed to acknowledge scientific uncertainty, the comprehensibility level exceeded the recommended 8th-grade level (e.g., average readability grade 10.7), and professional research organizations were notably absent. Narrators were mostly male (56.7%) and white-presenting (73.7%) (RQ2). The majority of the videos used multi-modal strategies (e.g., visual texts mixed with animation and voice-over narration) to communicate epigenetic information (RQ3). Conclusion: Findings highlight the need for professional research organizations to be more proactive in public epigenetic communication efforts. Increasing narrator demographic diversity could broaden audience reach. Evidence-based communication tools are needed for health or science communicators discussing epigenetics on social media.

Satellite DNA is long arrays of tandem repetitive DNA located often near the centromeres of chromosomes, whose function, or lack of, has been debated since its discovery. Although situated in heterochromatin, satellite DNA may be expressed as long noncoding RNAs (lncRNAs). Although there are a few examples of satellite lncRNAs being characterized, and functions suggested, how widespread and functionally important they may be for developmental processes is not understood. Here, we take an evolutionary approach to investigate satellite lncRNA expression in Drosophila spp. ovaries, a tissue whose development is well-characterized but where satellite expression has only been minimally explored. Using a publicly-available total RNAseq dataset, we find that 118/156 surveyed satellite DNAs were expressed across 10 species, with 33 satellites having high expression over 20 RPM. However, all but two of these expressed satellites (AAACTAC in D. virilis and ACAGACAGACAGG in D. ananassae) had higher read counts in a sister smallRNA dataset, suggesting that most satellite transcripts primarily serve as precursors for piRNA biogenesis. The two "stand-alone" lncRNAs were highly strand-biased, with 96-97% of the total reads coming from one strand. We further investigated AAACTAC expression with RNA FISH and found the transcript is specifically present in the oocyte nucleus following a dynamic spatiotemporal pattern, with the highest expression in stage 3-5 oocytes. The transcription pattern of AAACTAC is conserved in the three other virilis clade species that contain this satellite DNA. Further, we found expression of unrelated satellites in more distantly related D. borealis and littoralis both in the oocyte and the nurse cells. Overall, our work identifies a novel lncRNA AAACUAC found in the early oocyte nucleus, which is conserved across ~5 MY of evolution, and is therefore a strong candidate for the discovery of novel functions of satellite lncRNAs in development.

Importance: With emerging gene-targeted therapies in amyotrophic lateral sclerosis (ALS), gene discoveries and genetic diagnoses provide a crucial path to treatment. Pathogenic variants with moderate effect or incomplete penetrance, however, remain unidentified in genome-wide association studies and can appear sporadic in small modern-day pedigrees. Lack of recognition of familial clustering of ALS, in turn, limits opportunities for gene discovery, genetic diagnosis, risk counseling, and treatment. Objective: To determine the power of automated reconstruction of extended pedigrees, integrating archive records and genetic relatedness, in gene-discovery studies. Design: Retrospective observational study of Dutch ALS patients with the C9orf72 hexanucleotide repeat expansion (HRE), combining clinical family history, civil records, and genome-wide genotyping for relatedness and identity-by-descent (IBD) inference. Setting: National, population-based ALS cohort from the Netherlands and digitized population archives enabling systematic reconstruction of extended pedigrees. Participants: Individuals with ALS and a confirmed C9orf72 HRE. Participants must have provided a clinical family history and traceable Dutch ancestry documented in population archives. Main Outcomes and Measures: The primary outcome was the proportion of C9orf72 HRE carriers with newly identified (distant) relatives with ALS compared with clinical family history. The secondary outcome was the precision of IBD-based methods to fine-map the C9orf72 HRE. Other outcomes included phenotypic similarities between distantly related patients. Results: Among 238 C9orf72 HRE carriers, 91 could be included in one of 39 extended pedigrees dating back to ~1800, with relationships up to the eighth degree of relatedness. Compared with clinical family history alone, our approach increased the number of identified relationships by 2.5-fold. Genome-wide IBD analysis revealed shared haplotypes encompassing the C9orf72 HRE in 94% of pedigrees by [≥]7 meioses in 25.7-127.8 centimorgans total IBD shared. Conclusions and Relevance: Large-scale interrogation of archives facilitates reconstruction of extended pedigrees for ALS patients carrying the C9orf72 HRE. This combined genealogical-genetic approach supports the reclassification of apparently sporadic cases, facilitates the discovery of new disease-causing variants in ALS, and is generalizable to other late-onset neurodegenerative diseases. Automated pedigree reconstruction from genealogical data and visualization in an interactive databrowser are implemented in the open-source Mangrove software.

Background The detrimental impact of alcohol consumption on the gut microbiome is well-established. However, less is known about how alcohol exposure during pregnancy affects the maternal gut and vaginal microbiota, or how these microbial changes relate to subsequent infant diagnosis of fetal alcohol spectrum disorder (FASD). We therefore investigated associations between self-reported alcohol use during pregnancy, infant FASD diagnosis, and maternal gut and vaginal microbiota. Methods Fecal samples (n = 207) and vaginal swabs (n = 28) from pregnant participants recruited through antenatal clinics in the Western Cape Province of South Africa were profiled by 16S rRNA V1-V2 amplicon sequencing. Maternal alcohol use was assessed using Alcohol Use Disorder Identification Test (AUDIT) scores, and FASD was diagnosed in infants using revised Institute of Medicine criteria. Microbial diversity, taxonomic profiles and PICRUSt2-predicted functional pathways were analyzed using vegan, phyloseq and MaAsLin3. Results Maternal AUDIT scores were negatively associated with maternal gut microbiota richness, Shannon, and Inverse Simpson diversity (p < 0.05). Observed richness was also reduced in participants whose infants were diagnosed with FASD (p = 0.046). Gut microbiota community structure was not significantly associated with alcohol use or infant FASD diagnosis. However, taxonomic and functional analysis suggested gram-positive taxa depletion with alcohol use and FASD diagnosis, and impaired one-carbon metabolism among participants with infants diagnosed with FASD. Vaginal microbiota diversity and composition were not associated with alcohol use or infant diagnosis. Conclusions This is the first human study to investigate the maternal gut and vaginal microbiota in relation to alcohol use during pregnancy and infant FASD outcomes. Our findings suggest that alcohol use is associated with maternal gut microbiota disruption, with potential implications for FASD development in exposed infants. Further investigation of alcohol-associated maternal microbial disturbances may inform microbiota-targeted strategies to improve maternal and infant health linked to alcohol use.

Cross-beaks are deemed a threat to poultry health, productivity, and animal welfare. Nevertheless, due to sporadic cases, heterogeneity of gene loci and incomplete dominance, the molecular mechanism of cross-beak formation, especially the degree of cross, is not yet clear. Thus, we screen key genes and reveal the possible phenotypic formation mechanism of cross-beak by comparison with different degrees of deformity in Huiyang Bearded chickens by compare whole-genome resequencing-based variant analysis. Comparative analysis between cross-beak and normal-beaked chickens identified differential variants in several candidate genes, including CDH11, CTNNAL1, NRXN3, NRXN1, CDH5, SDC3, and DHFR. Genes harboring these variants were enriched in pathways related to cell adhesion molecules and metabolic processes, with functional annotations involving cell-cell adhesion and neural crest cell migration. Comparative analysis between chickens with severe and slight cross-beak deformities identified additional candidate genes, including MRPL21, NSUN2, DDX55, GNB3, and NFKB2. These genes were associated with enriched terms and pathways related to focal adhesion, amyotrophic lateral sclerosis, steroid 7 -hydroxylase activity, and skin-barrier establishment. These findings provide a preliminary catalogue of genetic variants and candidate genes for future functional studies of cross-beak development and severity in chickens.

Introduction. Hypertrophic cardiomyopathy (HCM) is characterized by clinical and genetic heterogeneity. Age of manifestation, clinical and anatomical phenotypes of HCM vary significantly. This study discusses genetic causes and reconstructive surgery results for patients with particular intracardiac phenotype - diffused generalized HCM (DG-HCM). Methods: personal and familial medical history, general examination, 12-lead resting ECG, 24-hour ECG Holter monitoring, transthoracic and transesophageal EchoCG, cardiac MRI with gadolinium enhancement. A ten-gene panel was sequenced by IonTorrent PGM. Mutational screening in patients with suspected multisystemic diseases was performed by Sanger sequencing. Results: 170 patients with obstructive HCM (oHCM) requesting genetic counseling and surgical correction of HCM were evaluated. We distinguished particular DG-HCM subtype of oHCM (diffuse hypertrophy of IVS, LV free walls, papillary muscles displaced towards the LV apex) in 34 patients; 31 out of 34 underwent open heart reconstructive surgery. Patients with DG-HCM were younger at the time of surgery, had higher risk of SCD, and connective tissue dysplasia of the mitral valve. Hemodynamics normalization was observed in 1, 3, and 5 years after surgery. Eighteen ICDs were implanted; five patients experienced appropriate shocks. The genetic spectrum was enriched up to 30% by multisystem disorders. Mutations in "sarcomeric" genes were detected in 15%. Conclusion: Intracardiac phenotype of HCM may correlate with genetic cause and long-term prognosis. DG-HCM phenotype accounts for 20% oHCM patients and indications for open-heart surgery. Extended myectomy with parietal resection of papillary muscles and correction of mitral valve insufficiency provides long-term benefits for DG-HCM patients. Multisystem disorders in patients with DG-HCM should be of special attention. Study was supported by research project FURG-2024-0004.

Studies of resemblance for disorders and other traits measured at the binary (yes/no) level between relatives frequently contain individuals who are currently in the negative category but who will become positive in future. For example, a 10-year-old may develop depression in the future, but is as yet unaffected. Such censoring can substantially bias estimates of correlation between relatives. To overcome this problem we develop a model for the association between liability to a disorder, and its age at onset. The model is designed for data from pairs of relatives to enable estimation of the correlation between an individuals' liability to disorder and their age at onset. Usually, such information is not available at the individual level, because age at onset is uniquely available when onset has occurred. Lacking variation in disorder status, data from non-related persons cannot estimate the covariance between liability and age at onset. Data from relatives can resolve this issue when there is a correlation in liability between the relatives, because different age at onset distributions would be expected in concordant vs. discordant pairs of relatives. Greater severity and worse outcomes are often observed among those with earlier onset, so a correlation between disorder liability and age at onset seems likely in many cases. In this article we present the basic theory of the model, implemented as a mixture distribution, and an application to cannabis use in a Virginia Twin Study of Adolescent Behavioral Development. A negative association of (-.212) between age at onset an liability was found, with confidence intervals of -.263 to -.152, which do not cross zero. The method contrasts with Cox Proportional Hazards, in which disorder liability and onset timing are treated as a single dimension.

BackgroundLamins are major regulators of the spatial and functional organization of chromatin. Lamins at the nuclear periphery form the lamina that anchors heterochromatin to the nuclear envelope. A subpool of A-type lamins localizes in the nuclear interior, where they also bind to euchromatic genomic regions. A-type lamin properties and chromatin association are regulated by lamin-associated polypeptide 2alpha (LAP2). Here we systematically analyze, how LAP2 depletion affects chromatin organization, accessibility and gene expression on a genome-wide level. ResultsLAP2 depletion in mouse dermal fibroblasts positively and negatively affects chromatin accessibility and gene expression throughout the genome, which correlates with changes in chromatin association of A-type lamins and the nucleosomal remodeler proteins BRG1 and CHD4. In particular, A-type lamins bind to open chromatin regions close to BRG1 and CHD4 binding sites and deregulated genes, but do not directly accumulate on genes and BRG1 and CHD4-enriched sites. Unsupervised clustering of the datasets on LAP2-bound genomic regions confirms spreading of A-type lamins to active chromatin regions containing deregulated genes and an enrichment of chromatin remodelers on a subset of these genomic regions. ConclusionsLAP2 depletion in fibroblasts leads to a gross rearrangement of chromatin. Genome-wide chromatin reorganization is linked to spreading of A-type lamins to active chromatin regions and accompanied by a restriction of chromatin remodelers to a subset of active genomic regions. These changes correlate with changes in chromatin accessibility and gene expression throughout the genome, particularly in regions where lamin binding is gained in LAP2 knockout versus wildtype cells.

RationaleRecent viral metagenomic studies have identified a plethora of enzyme-encoding genes in Phycodnaviridae viruses that are not strictly required for viral replication. These enzymes hold an unexpected metabolic potential during the infection process with their specific green algae host. As neither their role in the infection process nor the subcellular localization of these proteins has been experimentally characterized, comparative sequences, structural and biochemical in silico analyses can help generate functional and localization hypotheses. MethodsIn a recent viral metagenomic dataset, we identified a collection of viral homologs involved in bilin biosynthesis: heme oxygenase (vHMOX1) and Phycocyanobilin:Ferredoxin oxidoreductase (vPcyA). Viral and algal homologues were compared through sequence analyses and AlphaFold3 structural predictions. Predicted biochemical properties were analyzed for their compatibility with subcellular compartments. Active site architecture and putative substrate binding were compared between viral and algal proteins using AlphaFold3 and experimentally resolved structures. ResultsViral HMOX1 and PcyA sequences are truncated compared to algal homologs, lacking the N-terminal extension associated with chloroplast targeting. However biochemical properties, including isoelectric point and surface charge distribution, are compatible with localization in chloroplast stroma. Structural comparisons reveal modifications in the viral HMOX1 active site, including partial substrate reorientation and substitutions of key residues, consistent with modified heme-binding properties. In contrast, vPcyA models show no significant differences to their algal counterparts. ConclusionsActive site remodeling in vHMOX1 protein models suggests that these viral homologues may have evolved distinct heme-binding properties. Unlike vPcyA, vHMOX1 homologs appear to have diverged more substantially from their algal counterparts, potentially reflecting functional specialization in the viral infection context. One sentence summary of key findingsOur bioinformatic analyses expand the repertoire of auxiliary metabolic genes in Phycodnaviridae by identifying a conserved heme degradation pathway, non-canonical vHMOX1/PcyA targeting and structural rearrangements surrounding the catalytic sites of viral HMOX1.

Temperature plays a central role in marine phytoplankton biogeographical dynamics, physiology and gene expression. Nonetheless, the transcriptional regulatory mechanisms controlling temperature acclimation in marine phytoplankton are yet to be characterized. Ostreococcus tauri was chosen as a model species for green marine phytoplankton due to its cellular and genomic simplicity, as well as its evolutionary position within the green lineage. In this study, epigenomic and transcriptomic data were integrated to characterize changes induced by temperature in the trimethylation of histone 3 at lysines 27 and 4 (H3K27me3 and H3K4me3) epigenetic marks established by the Polycomb (PcG) and Trithorax group (TrxG) complexes, respectively. H3K27me3 was found to be a repressive mark responding to temperature, showing predominantly significant increased levels at high temperatures. While H3K4me3 was associated with active transcription, presenting less evident variations in cultures acclimated to different temperatures. H3K27me3 was found only marginally associated with transposable elements, being mostly involved in the repression of specific biological processes, such as gene expression control by transcription factors, meiosis, motors proteins and cytoskeletal structures. No significant conservation was found between the H3K27me3 gene targets in the model plant Arabidopsis thaliana and Ostreococcus tauri. Nonetheless, transcriptions factors belonging to the MADS-box, WRKY and AP2 families were consistently repressed by H3K27me3 in both species, unveiling that, although the specific downstream targets of this epigenetic mark have diversified during evolution, its role in modulating higher order regulatory nodes remains evolutionary conserved.

The European leaf-toed gecko (Euleptes europaea) is a small, nocturnal gecko endemic to the western Mediterranean. As a phylogenetically distinctive member of the Gondwanan family Sphaerodactylidae, it represents an important species for studying Mediterranean island biogeography, adaptation, and reptile genome evolution. The species also occupies a key position for investigating the evolution of sex chromosomes, as geckos exhibit remarkable diversity and frequent transitions in sex-determination systems. We present a chromosome-level genome assembly of Euleptes europaea generated as part of the Vertebrate Genomes Project. The 1.8 Gb assembly has a scaffold N50 of 102.3 Mb (contig N50 27 Mb), with 21 chromosome-scale scaffolds corresponding to the known karyotype (2n = 42). The primary assembly has a BUSCO completeness of 97.80% (95.60% as single-copy), a k-mer completeness of 96.00%, and a k-mer quality value (QV) of 61.20. Repetitive elements account for 53.20% of the genome and genome annotation identified 18,633 protein-coding genes. This high-quality reference genome will facilitate studies of genome evolution, island adaptation, and sex chromosome evolution across geckos and other reptiles.

BackgroundThe capitulum of Asteraceae is a highly specialized inflorescence whose formation requires the coordinated regulation of multiple developmental processes, including floral organ identity and floral meristem determinacy. The LEAFY (LFY)-UNUSUAL FLORAL ORGANS (UFO) regulatory module is known to play an important role in flower development; however, naturally occurring mutations affecting this pathway have not been genetically characterized in gerbera (Gerbera hybrida). ResultsIn this study, we characterized a novel gerbera mutant identified during a commercial crossing program and named it marimo based on its green, spherical capitulum. Morphological observations revealed the repeated formation of secondary and tertiary floret-like organs within primary floret-like organs. Scanning electron microscopy showed that the epidermal structure of the green organs in marimo was similar to that of wild-type involucral bracts. RNA sequencing identified numerous differentially expressed genes between marimo and the wild type, and network and Gene Ontology analyses highlighted gene groups associated with flower development, reproductive organ differentiation, and tissue structure formation. RNA-seq analysis showed increased expression of LFY and reduced expression of GGLO1, a PISTILLATA/GLOBOSA-like B-class MADS-box gene, in the marimo mutant. RT-qPCR analysis of a segregating population further confirmed reduced GGLO1 expression in marimo-type individuals. In addition, a single-nucleotide deletion was identified in the coding region of UFO. This deletion was predicted to cause a frameshift and a premature stop codon. In selfed progeny of No. 251, the UFO genotype was fully associated with capitulum phenotype, and only individuals homozygous for the mutant allele exhibited the marimo phenotype. ConclusionsThese results indicate that the naturally occurring frameshift mutation in UFO is the strongest candidate variant underlying the marimo phenotype. RNA-seq analysis showed increased LFY expression and markedly reduced GGLO1 expression in the marimo mutant. Reduced activity of the LFY-UFO regulatory module may therefore have altered the expression of GGLO1 and other floral organ development-related genes despite the continued expression of LFY. These changes may have affected both floral organ identity and floral meristem determinacy, resulting in the formation of green involucral bract-like organs and the repeated production of floret-like organs. The marimo mutant provides a useful genetic resource for investigating capitulum development in Asteraceae and may also serve as breeding material for introducing novel ornamental traits into gerbera.

Summary/AbstractTelomere length has a significant impact on human health. Short telomeres cause age-related diseases, including pulmonary fibrosis, immunodeficiency, and bone marrow failure, while long telomeres predispose to cancer. Given the impact on human health, accurately measuring telomere length is important. A variety of methods have been developed over the past 40 years to measure telomere length. Many of these methods report only on the mean length of all of the telomere in the cell. Here, we describe the Telomere Profiling protocol using Oxford Nanopore Technologies (ONT) based on long read sequencing that can accurately measure chromosome specific telomere length.

Purpose: Age-related Macular Degeneration (AMD), a degenerative disease of aging, leads to central vision loss and has a strong genetic risk. Genetic heritability, used to quantify genetic influence on a trait, has mainly focused on twin study designs but these are vulnerable to bias. Studying relatives beyond twins is necessary to bring clarity to the genetic burden of AMD and help focus the search for additional genetic risk loci. Methods: Through both single nucleotide polymorphism (SNP) and pedigree-based heritability methods, the heritability of AMD was analyzed using relationship informed analyses of families from an Amish population (n = 525). AMD status was determined using the Beckman grading scale (285 controls and 240 cases). An estimate of genetic relatedness preceded SNP heritability estimation, whereas the pedigree heritability model utilized genealogical reports. Primary models were adjusted for age, sex, and population structure. A comparison of SNP- and pedigree-based models followed heritability estimation. Sensitivity models adjusting for all possible combinations of three known strong AMD genetic risk variants were constructed. Results: SNP heritability is 55% +/- 13% (p= 9.87e-06) and the pedigree heritability is 49% +/- 18% (p= 3.06e-04). The sensitivity analyses revealed that the estimates were robust to changes in the inclusion of AMD variants as covariates. Conclusions: These heritability estimates support existing twin and SNP-based AMD heritability estimates and corroborate the substantial involvement of genetics in AMD. Adjusting for known AMD variants revealed that additional genetic contribution exists, supporting a large polygenic effect in AMD.

Background. The imprecision of current metrics to capture the complex genetic admixture and racial identity among Hispanic/Latino individuals in the United States [US] is a concern. We examined the relationship of self-reported race and genetic ancestry with hypertension [HTN] among Hispanics/Latinos. Methods. Cross-sectional study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), including 10,586 Hispanic/Latino unrelated adults. Genetic ancestry: West African [AA], Amerindian [AI], and European [EA]. Self-reported race: White, Black, Native American, or Multiple/Missing (More than one race or Unknown/Not reported/Refused). HTN: systolic (SBP) [&ge;]130 mmHg, diastolic blood pressure (DBP) [&ge;]80 mmHg, and/or use of HTN medications. Age- and sex adjusted models were used. Results. Self-reported race was White (38{middle dot}6%), Black (3{middle dot}6%), Native American (4{middle dot}1%), and Multiple/Missing (53{middle dot}7%), with Unknown/Not reported/Refused representing 32{middle dot}7%. Black and White Hispanics/Latinos had the greatest AA (55{middle dot}7%) and EA (69{middle dot}3%) ancestries, respectively. Each 10% AA increase was associated with OR 1{middle dot}15, SBP beta +0{middle dot}9 mmHg, and DBP beta +0{middle dot}7 mmHg. Conversely, each 10% AI increase was associated with OR 0{middle dot}83, SBP beta -0{middle dot}4 mmHg, and DBP beta -0{middle dot}6 mmHg. HTN prevalence was highest among those with Black race or in the highest AA quantile (45{middle dot}6% and 48{middle dot}0%, respectively), and lowest among those with Native American race or in the highest AI quantile (37{middle dot}6% and 26{middle dot}7%, respectively). Conclusion. One-third of Hispanics/Latinos did not self-report race. Black or White self-reporting race did somewhat relate to AA or EA ancestry, respectively. HTN profiles were related to self-reported race and genetic ancestry in this admixed population.

How morphological complexity evolves is still enigmatic. While there is evidence in algae and plants as well as animals that diversification of the repertoire of transcription factors (TF) is causative for evolution of organismal complexity, there are many examples from lineages that follow their own way of complexity evolution, for example by expansion of particular families. For land plants, correlation of the size of the TF complement with number of cell types (as a proxy for morphological complexity) has been shown, and several families were identified as candidates to drive complexity evolution. Here, we expand a previously available dataset of cell type numbers from 12 to 82 proteomes and introduce a four class body plan scheme. We find that the total TF complement correlates with the number of cell types of Archaeplastida (primary plastid bearing plants and algae). We used TabPFN (Tabular Prior-data Fitted Network) for binary (uni- vs. multicellularity) as well as for four class Bauplan classification. TabPFN is able to predict the morphological complexity with high accuracy. This approach allows to determine organismal complexity based on the gene space of an organism. Based on our results, we can confirm that plant morphological evolution is driven by gain and expansion of TF families.