Fiskerrosenthal9936

HIF (Hypoxia-inducible factor) gene family members function as master regulators of cellular and systemic oxygen homeostasis during changes in oxygen availability. Qinghai-Tibet Plateau is a natural laboratory for for long-term hypoxia and cold adaptation. In this context, T. scleroptera that is restricted to >3500 m high-altitude freshwater rivers was selected as the model to compare with a representative species from the plain, P. dabryanus. We cloned different HIF-α and carried out a phylogenetic analysis from invertebrates to vertebrates for identifying HIF-α genes and analyzing their evolutionary history. Intriguingly, the HIF-α has undergone gene duplications might be due to whole-genome duplication (WGD) events during evolution. PAML analysis indicated that HIF-1αA was subjected to positive selection acted on specific sites in Triplophysa lineages. To investigate the relationship between hypoxia adaptation and the regulation of HIF-α stability by pVHL in plateau and plain fish, a series of experiments were carried out. Comparison the luciferase transcriptional activity and protein levels of HIF-αs and the differing interactions of HIF-αs with pVHL, show clear differences between plateau and plain fish. T. scleroptera pVHL could enhance HIF-α transcriptional activity under hypoxia, and functional validation through pVHL protein mutagenesis showed that these mutations increased the stability of HIF-α and its hetero dimerization affinity to ARNT. Our research shows that missense mutations of pVHL induced evolutionary molecular adaptation in Triplophysa fishes living in high altitude hypoxic environments.Genome-wide association studies (GWAS) have successfully mapped thousands of loci associated with complex traits. These associations could reveal the molecular mechanisms altered in common complex diseases and result in the identification of novel drug targets. However, GWAS have also left a number of outstanding questions. In particular, the majority of disease-associated loci lie in non-coding regions of the genome and, even though they are thought to play a role in gene expression regulation, it is unclear which genes they regulate and in which cell types or physiological contexts this regulation occurs. This has hindered the translation of GWAS findings into clinical interventions. In this review we summarize how these challenges have been addressed over the last decade, with a particular focus on the integration of GWAS results with functional genomics datasets. Firstly, we investigate how the tissues and cell types involved in diseases can be identified using methods that test for enrichment of GWAS variants in genomic annotations. Secondly, we explore how to find the genes regulated by GWAS loci using methods that test for colocalization of GWAS signals with molecular phenotypes such as quantitative trait loci (QTLs). Finally, we highlight potential future research avenues such as integrating GWAS results with single-cell sequencing read-outs, designing functionally informed polygenic risk scores (PRS), and validating disease associated genes using genetic engineering. These tools will be crucial to identify new drug targets for common complex diseases.Homozygous and compound heterozygous mutations in GNB5 gene have been associated with a wide spectrum of clinical presentations, ranging from neurodevelopmental issues with or without cardiac arrhythmia (LADCI) to severe developmental delay with epileptic encephalopathy, retinal dystrophy, and heart rhythm abnormalities (IDDCA). While missense or missense/non-sense mutations usually lead to milder form, the biallelic loss of function of GNB5 gene causes the severe multisystemic IDDCA phenotype. So far, only 27 patients have been described with GNB5-associated disease. We report the first case of a patient carrying a homozygous 15q21.2 microdeletion, encompassing GNB5 and the two contiguous genes BCL2L10 and MYO5C. The clinical features of the child are consistent with the severe IDDCA phenotype, thus confirming the GNB5 loss-of-function mechanism in determining such presentation of the disease.Rattan is regarded as one of the major non-timber forest products, second only to wood and bamboo, worldwide. Although the published genomes of Calamus simplicifolius and Daemonorops jenkinsiana have facilitated genome-wide gene functional analyses, coexpression networks (CENs) provide more comprehensive and complete annotations of gene function at the transcriptome level. Thus, we analyzed the CENs of the two rattans, C. simplicifolius and D. jenkinsiana, by integrating the genome sequences and analyzing in-house transcriptome data from different development stages of their cirri using a well-developed strategy. A total of 3,504 and 3,027 functional modules were identified in C. Coleonol price simplicifolius and D. jenkinsiana, respectively, based on a combination of CENs, gene family classification, and function enrichment tools. These modules covered the major developmental processes, including photosynthesis, lignin biosynthesis, flavonoid biosynthesis, and phenylpropanoid biosynthesis. Reference annotations were refined using CENs and functional modules. Moreover, we obtained novel insights into the regulation of cirrus growth and development in rattans. Furthermore, Rattan-NET (http//rattan.bamboogdb.org/), an online database with analysis tools for gene set enrichment analysis, module enrichment, network comparison analysis, and cis-element analysis, was constructed for the easy analysis of gene function and regulation modules involved in the growth and development of cirri in rattans.Artificial allopolyploids derived from the genera Triticum and Aegilops have been used as genetic resources for wheat improvement and are a classic example of evolution via allopolyploidization. In this study, we investigated chromosomes and subgenome transmission behavior in the newly formed allopolyploid of wheat group via multicolor Fluorescence in situ hybridization (mc-FISH), using pSc119.2, pTa535, and (GAA)7 as probe combinations, to enabled us to precisely identify individual chromosomes in 381 S3 and S4 generations plants derived from reciprocal crosses between Ae. ventricosa (DvDvNvNv) and T. turgidum (AABB). A higher rate of aneuploidy, constituting 66.04-86.41% individuals, was observed in these two early generations. Of the four constituent subgenomes, Dv showed the highest frequency of elimination, followed by Nv and B, while A was the most stable. In addition, structural chromosomal changes occurred ubiquitously in the selfed progenies of allopolyploids. Among the constituent subgenomes, B showed the highest number of aberrations.