Genes最新文献

Background: Interspecific hybridization between relative species Cobitis taenia (with a diploid genome designated as TT), Cobitis elongatoides (EE) and Cobitis tanaitica (NN) and the successive polyploidization with transitions from sexuality to asexuality experienced by triploid Cobitis hybrids likely influence their chromosomal rearrangements, including rearrangements of ribosomal DNA (rDNA) distribution patterns. Previously, we documented distinct karyotypic differences: C. elongatoides exhibited bi-armed chromosomes while C. taenia showed uni-armed chromosomes with rDNA-positive hybridization signals, respectively. Methods: In this study, fluorescence in situ hybridization (FISH) with 5S rDNA and 28S rDNA probes was used to analyze and compare chromosomal distribution patterns of rDNAs in clonally reproduced triploid Cobitis hybrids of different genomic constitutions ETT, ETN, EEN and EET (referred to using acronyms denoting the haploid genomes of their parent species), and their parental species. Results:Cobitis triploid hybrids exhibited intermediate karyotypes with ribosome synthesis sites on chromosomes inherited from both parents, showing no evidence of nucleolar dominance. The rDNA pattern derived from the C. elongatoides genome was more stable in the hybrids' karyotypes. Two and one submetacentric chromosomes with co-localized rDNAs were effective markers to ascertain C. elongatoides diploid (EE) and haploid (E) genomes within the genome of triploid hybrids, respectively. Fewer 5S rDNA loci were observed in diploid (TT) and haploid (T) chromosome sets from C. taenia in ETT and EET females. C. taenia and C. tanaitica exhibited similar rDNA distribution patterns. Conclusions: The karyotypes of triploid Cobitis hybrids reflect the genomic contributions of their parental species. Variability in rDNA distribution patterns suggests complex genomic interactions in Cobitis hybrids resulting from polyploidization and hybridization, potentially influencing their reproductive potential.

22q11.2 is a region prone to chromosomal rearrangements due to the presence of eight large blocks of low-copy repeats (LCR22s). The 3 Mb 22q11.2 "typical deletion", between LCR22-A and D, causes a fairly well-known clinical picture, while the effects of smaller CNVs harbored in this interval are still to be fully elucidated. Nested deletions, flanked by LCR22B-D, LCR22B-C, or LCR22C-D, are very rare and are collectively described as "central deletions". The LCR22C-D deletion (CDdel) has never been separately analyzed. In this paper, we focused only on CDdel, evaluating its gene content and reviewing the literature and public databases in order to obtain new insights for the classification of this CNV. At first glance, CDdels are associated with a broad phenotypic spectrum, ranging from clinically normal to quite severe phenotypes. However, the frequency of specific clinical traits highlights that renal/urinary tract abnormalities, cardiac defects, and neurological/behavioral disorders are much more common in CDdel than in the general population. This frequency is too high to be fortuitous, indicating that CDdel is a predisposing factor for these phenotypic traits. Among the genes present in this interval, CRKL is an excellent candidate for cardiac and renal defects. Even if further data are necessary to confirm the role of CDdels, according to our review, this CNV fits into the class of 'likely pathogenic' CNVs.

Background/objectives: Cold stress poses a significant threat to Asian rice cultivation, disrupting important physiological processes crucial for seedling establishment and overall plant growth. It is, thus, crucial to elucidate genetic pathways involved in cold stress tolerance response mechanisms.

Methods: We mapped OsUBC7, a Radiation-sensitive 6 (RAD6)-type homolog of rice, to a low-temperature seedling survivability (LTSS) QTL and used genomics, molecular genetics, and physiological assays to assess its role in plant resilience against low-temperature stress.

Results: OsUBC7 is cold responsive and has higher expression levels in cold-tolerant japonica than cold-sensitive indica. Overexpression of OsUBC7 enhances LTSS of indica and freezing tolerance of Arabidopsis, increases levels of soluble sugars and chlorophyll A, boosts leaf development after cold exposure, and increases leaf cell numbers and plants size, but it does not affect membrane stability after cold stress exposure. Additionally, OsUBC7 has a positive role for germinability in the presence of salt and for flowering and yield-related traits. The OsUBC7 protein physically interacts with the developmental stage-specific and histone-modifying E3 ligases OsRFPH2-12 and OsHUB1/2, respectively, and potential target genes such as cell cycle dependent kinases were identified.

Conclusions: OsUBC7 might contribute to cold resilience by regulating sugar metabolism to provide energy for promoting cellular homeostasis restoration after cold stress exposure via new cell growth, particularly in leaf cells crucial for photosynthesis and metabolic activity, possibly by interacting with cell cycle regulating proteins. Overall, the present study suggests that OsUBC7 may be involved in plant development, reproduction, and stress adaptation, and contributes to a deeper understanding of rice plant cold stress tolerance response mechanisms. OsUBC7 may be a promising candidate for improving crop productivity and resilience to stressful environments.

Background/objectives: Internalizing disorders, including depression and anxiety, are major contributors to the global burden of disease. While the genetic architecture of these disorders in adults has been extensively studied, their early-life genetic mechanisms remain underexplored, especially in non-European populations. This study investigated the genetic mechanisms underlying internalizing symptoms in a cohort of Latin American children.

Methods: This study included 1244 Brazilian children whose legal guardians completed the Child Behavior Checklist (CBCL) questionnaire. Genotyping was performed using the Illumina HumanOmni 2.5-8v1 BeadChip.

Results: The genome-wide association analysis revealed a significant association of rs7196970 (p = 4.5 × 10^-8, OR = 0.61), in the ABCC1 gene, with internalizing symptoms. Functional annotation highlighted variants in epigenetically active regulatory regions, with multiple variants linked to differential expression of ABCC1 across several human tissues. Pathway enrichment analysis identified 42 significant pathways, with notable involvement in neurobiological processes such as glutamatergic, GABAergic, and dopaminergic synapses.

Conclusions: This study identifies ABCC1 variants as novel genetic factors potentially associated with early-life internalizing symptoms. These results may contribute to future research on targeted interventions for childhood internalizing conditions.

Background: The patterns of inbreeding coefficients (F_IS) and fine spatial genetic structure (FSGS) were evaluated regarding the mating system and inbreeding depression of food-deceptive orchids, Dactylorhiza majalis, Dactylorhiza incarnata var. incarnata, and Dactylorhiza fuchsii, from NE Poland.

Methods: We used 455 individuals, representing nine populations of three taxa and AFLPs, to estimate percent polymorphic loci and Nei's gene diversity, which are calculated using the Bayesian method; F_IS; F_ST; FSGS with the pairwise kinship coefficient (Fij); and AMOVA in populations.

Results: We detected a relatively high proportion of polymorphic fragments (40.4-68.4%) and Nei's gene diversity indices (0.140-0.234). The overall F_IS was relatively low to moderate (0.071-0.312). The average Fij for the populations of three Dactylorhiza showed significantly positive values, which were observed between plants at distances of 1-10 m (20 m). F_ST was significant in each Dactylorhiza taxon, ranging from the lowest values in D. fuchsii and D. majalis (0.080-0.086, p < 0.05) to a higher value (0.163, p < 0.05) in D. incarnata var. incarnata. Molecular variance was the highest within populations (76.5-86.6%; p < 0.001).

Conclusions: We observed concordant genetic diversity patterns in three food-deceptive, allogamous, pollinator-dependent, and self-compatible Dactylorhiza. F_IS is often substantially higher than Fij with respect to the first class of FSGSs, suggesting that selfing (meaning of geitonogamy) is at least responsible for homozygosity. A strong FSGS may have evolutionary consequences in Dactylorhiza, and combined with low inbreeding depression, it may impact the establishment of inbred lines of D. majalis and D. incarnata var. incarnata.

Background/objectives: Cowpea is an important legume crop in sub-Saharan Africa (SSA) and beyond. However, access to phosphorus (P), a critical element for plant growth and development, is a significant constraint in SSA. Thus, it is essential to have high P-use efficiency varieties to achieve increased yields in environments where little-to- no phosphate fertilizers are applied.

Methods: In this study, crop phenology, yield, and grain P efficiency traits were assessed in two recombinant inbred line (RIL) populations across ten environments under high- and low-P soil conditions to identify traits' response to different soil P levels and associated quantitative trait loci (QTLs). Single-environment (SEA) and multi-environment (MEA) QTL analyses were conducted for days to flowering (DTF), days to maturity (DTM), biomass yield (BYLD), grain yield (GYLD), grain P-use efficiency (gPUE) and grain P-uptake efficiency (gPUpE).

Results: Phenotypic data indicated significant variation among the RILs, and inadequate soil P had a negative impact on flowering, maturity, and yield traits. A total of 40 QTLs were identified by SEA, with most explaining greater than 10% of the phenotypic variance, indicating that many major-effect QTLs contributed to the genetic component of these traits. Similarly, MEA identified 23 QTLs associated with DTF, DTM, GYLD, and gPUpE under high- and low-P environments. Thirty percent (12/40) of the QTLs identified by SEA were also found by MEA, and some of those were identified in more than one P environment, highlighting their potential in breeding programs targeting PUE. QTLs on chromosomes Vu03 and Vu08 exhibited consistent effects under both high- and low-P conditions. In addition, candidate genes underlying the QTL regions were identified.

Conclusions: This study lays the foundation for molecular breeding for PUE and contributes to understanding the genetic basis of cowpea response in different soil P conditions. Some of the identified genomic loci, many being novel QTLs, could be deployed in marker-aided selection and fine mapping of candidate genes.

Background/objectives: The failure of physiological left-right (LR) patterning, a critical embryological process responsible for establishing the asymmetric positioning of internal organs, leads to a spectrum of congenital abnormalities characterized by laterality defects, collectively known as "heterotaxy". MMP21 biallelic variants have recently been associated with heterotaxy syndrome and congenital heart defects (CHD). However, the genotype-phenotype correlations and the underlying pathogenic mechanisms remain poorly understood.

Methods: Patients harboring biallelic MMP21 missense variants who underwent diagnostic genetic testing for CHD or heterotaxy were recruited at the Institute for Maternal and Child Health-I.R.C.C.S. "Burlo Garofolo". Additionally, a literature review on MMP21 missense variants was conducted, and clinical data from reported patients, along with molecular data from in silico and modeling tools, were collected.

Results: A total of 18 MMP21 missense variants were reported in 26 patients, with the majority exhibiting CHD (94%) and variable extra-cardiac manifestations (64%). In our cohort, through Whole-Exome Sequencing (WES) analysis, the missense p.(Met301Ile) variant was identified in two unrelated patients, who both presented with heterotaxy syndrome.

Conclusions: Our comprehensive analysis of MMP21 missense variants supports the pathogenic role of the p.(Met301Ile) variant and provides significant insights into the disease pathogenesis. Specifically, missense variants are distributed throughout the gene without clustering in specific regions, and phenotype comparisons between patients carrying missense variants in compound heterozygosity or homozygosity do not reveal significant differences. These findings may suggest a potential loss-of-function mechanism for MMP21 missense variants, especially those located in the catalytic domain, and highlight their critical role in the pathogenesis of heterotaxy syndrome.

(1) Background: Animal growth is a complex process, involving the coordination of a wide variety of genes, non-coding RNAs, and pathways. Circular RNAs (circRNAs) belong to a novel class of functional non-coding RNAs (ncRNAs). They have a distinctive ring structure and are involved in various biological processes, including the proliferation, differentiation, and apoptosis of muscle cells. The Pacific abalone Haliotis discus hannai is an economically valuable mollusk species cultivated in China. However, the modulation of muscle growth by circRNAs in this species is poorly understood. (2) Methods: In this study, we analyzed the muscle transcriptomes of 6 H. discus hannai specimens: three small (S_HD) and three large (L_HD) groups via RNA-seq and bioinformatics technology. (3) Results: The results indicated the presence of 11,744 circRNAs in abalone adductor muscle. Furthermore, the L_HD group had 250 significantly differentially expressed circRNAs (106 upregulated and 144 downregulated) relative to the S_HD group. Moreover, the bioinformatics assessment revealed that circRNAs were related to lipid transporter activity, lipid biosynthetic process, fat digestion and absorption, the single-organism metabolic process, the thyroid hormone signaling pathway, and the hippo signaling pathway, which regulates growth. Seventeen key candidate circRNAs were identified, and a core functional circRNA-miRNA-mRNA network associated with abalone muscle growth was described. Gene expression was verified using qRT-PCR, confirming the accuracy of the RNA-seq data. (4) Conclusion: Overall, this investigation furnishes novel evidence for the potential muscle growth modulatory mechanisms in Pacific abalone. These high-quality circRNA data of abalone muscle provide a reference for functional studies on the abalone genome.

Background/objectives: The OTOG gene is responsible for autosomal recessive non-syndromic sensorineural hearing loss and is assigned as DFNB18B. To date, 44 causative OTOG variants have been reported to cause non-syndromic hearing loss. However, the detailed clinical features for OTOG-associated hearing loss remain unclear.

Methods: In this study, we analyzed 7065 patients with non-syndromic hearing loss (mean age 26.4 ± 22.9 years, 2988 male, 3855 female, and 222 without gender information) using massively parallel DNA sequencing for 158 target deafness genes. We identified the patients with biallelic OTOG variants and summarized the clinical characteristics.

Results: Among the 7065 patients, we identified 14 possibly disease-causing OTOG variants in 26 probands, with 13 of the 14 variants regarded as novel. Patients with OTOG-associated hearing loss mostly showed congenital or childhood-onset hearing loss. They were considered to show non-progressive, mild-to-moderate hearing loss. There were no symptoms that accompanied the hearing loss in OTOG-associated hearing loss patients.

Conclusions: We confirmed non-progressive, mild-to-moderate hearing loss as the clinical characteristics of OTOG-associated hearing loss. These findings will contribute to a better understanding of the clinical features of OTOG-associated HL and will be useful in clinical practice.

Background: Eukaryotic RNA polymerase I consists of 12 or 11 core subunits and three dissociable subunits, Rrn3, A34, and A49. The A34 and A49 subunits exist as a heterodimer. In silico analysis of the A34 family of transcription factors demonstrates a commonly shared domain structure despite a lack of sequence conservation, as well as N-terminal and C-terminal disordered regions. The common structure of A34 has an N-terminal disordered region followed by a dimerization domain that, in conjunction with A49, contributes to a fold that resembles the TFIIF core. This in turn is followed by a short region that cryo-EM demonstrates resembles an arm and intimately interacts with the PolR1A, PolR1B, and PolR1C subunits of Pol I.

Analyses: This Pol I-binding domain is then followed by a region that is not resolved in cryo-EM and is predicted to be intrinsically disordered. Interestingly, the size/length of this disordered structure increases from yeast to humans, and is composed of repeats with unique sequence and biochemical features that also increase in number. Further analyses of the A34 CTD (carboxy-terminal domain) indicate that it has a high probability of undergoing liquid-liquid phase separation.

Conclusions: We suggest that this intrinsically disordered domain found in the A34 family of Pol I transcription factors serves a function similar to the CTD of the PolR2A subunit in coordinating transcription initiation and elongation and RNA processing. Lastly, we propose that dynamic acetylation of PAF49 may regulate interactions of the intrinsically disordered CTD and thereby specify liquid-liquid phase separations. Overall, we propose a new paradigm for a repeat-containing CTD in Pol I transcription.