The molecular basis of increased hemoglobin in Andean Aymara highlanders is unknown. We conducted an integrative analysis of whole-genome-sequencing and granulocytes transcriptomics from Aymara and Europeans in Bolivia to explore genetic basis of the Aymara high hemoglobin. Differentially expressed and spliced genes in Aymaras were associated with inflammatory and hypoxia-related pathways. We identified transcripts with 4th or 5th exon skipping of NFKB1 (AS-NFKB1), key part of NF-kB complex, and their splicing quantitative trait loci; these were increased in Aymaras. AS-NFKB1 transcripts correlated with both transcripts and protein levels of inflammatory and HIF-regulated genes, including hemoglobin. While overexpression of the AS-NFKB1 variant led to increased expression of inflammatory and HIF-targeted genes; under inflammatory stress, NF-kB protein translocation to the nucleus was attenuated, resulting in reduced expression of these genes. Our study reveals AS-NFKB1 splicing events correlating with increased hemoglobin in Aymara and their possible protective mechanisms against excessive inflammation.

• MeSH
• alternativní sestřih * genetika   MeSH
• dospělí MeSH
• exony genetika   MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa genetika   metabolismus   MeSH
• granulocyty metabolismus   MeSH
• hemoglobiny * metabolismus   genetika   MeSH
• lidé MeSH
• lokus kvantitativního znaku MeSH
• NF-kappa B - podjednotka p50 * metabolismus   genetika   MeSH
• regulace genové exprese MeSH
• transkriptom MeSH
• zánět * genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Bolívie MeSH
• Názvy látek
• faktor 1 indukovatelný hypoxií - podjednotka alfa MeSH
• hemoglobiny * MeSH
• NF-kappa B - podjednotka p50 * MeSH
• NFKB1 protein, human MeSH Prohlížeč

BACKGROUND/OBJECTIVES: Arachnids are a megadiverse arthropod group. The present study investigated the chromosomes of pedipalpid tetrapulmonates (orders Amblypygi, Thelyphonida, Schizomida) and two arachnid orders of uncertain phylogenetic placement, Ricinulei and Solifugae, to reconstruct their karyotype evolution. Except for amblypygids, the cytogenetics of these arachnid orders was almost unknown prior to the present study. METHODS: Chromosomes were investigated using methods of standard (Giemsa-stained preparations, banding techniques) and molecular cytogenetics (fluorescence in situ hybridization, comparative genomic hybridization). RESULTS AND CONCLUSIONS: New data for 38 species, combined with previously published data, suggest that ancestral arachnids possessed low to moderate 2n (22-40), monocentric chromosomes, one nucleolus organizer region (NOR), low levels of heterochromatin and recombinations, and no or homomorphic sex chromosomes. Karyotypes of Pedipalpi and Solifugae diversified via centric fusions, pericentric inversions, and changes in the pattern of NORs and, in solifuges, also through tandem fusions. Some solifuges display an enormous amount of constitutive heterochromatin and high NOR number. It is hypothesized that the common ancestor of amblypygids, thelyphonids, and spiders exhibited a homomorphic XY system, and that telomeric heterochromatin and NORs were involved in the evolution of amblypygid sex chromosomes. The new findings support the Cephalosomata clade (acariforms, palpigrades, and solifuges). Hypotheses concerning the origin of acariform holocentric chromosomes are presented. Unlike current phylogenetic hypotheses, the results suggest a sister relationship between Schizomida and a clade comprising other tetrapulmonates as well as a polyploidization in the common ancestor of the clade comprising Araneae, Amblypygi, and Thelyphonida.

• Klíčová slova
• Ricinulei, heterochromatin, holocentric, nucleolus organizer region, polyploidy, sex chromosome, solifuge, somatic pairing, spider, telomere,
• MeSH
• fylogeneze * MeSH
• hybridizace in situ fluorescenční MeSH
• karyotyp * MeSH
• molekulární evoluce * MeSH
• organizátor jadérka genetika   MeSH
• pavoukovci * genetika   klasifikace   MeSH
• srovnávací genomová hybridizace MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Crop breeding advancement is hindered by the imperfection of methods to reveal genes underlying key traits. Genome-wide Association Study (GWAS) is one such method, identifying genomic regions linked to phenotypes. Post-GWAS analyses predict candidate genes and assist in causative mutation (CM) recognition. Here, we assess post-GWAS approaches, address limitations in omics data integration and stress the importance of evaluating associated variants within a broader context of publicly available datasets. Recent advances in bioinformatics tools and genomic strategies for CM identification and allelic variation exploration are reviewed. We discuss the role of markers and marker panel development for more precise breeding. Finally, we highlight the perspectives and challenges of GWAS-based CM prediction for complex quantitative traits.

• Klíčová slova
• Causal gene, Causative mutation, Crop breeding, GWAS, Molecular markers,
• MeSH
• celogenomová asociační studie * MeSH
• fenotyp MeSH
• genetické markery MeSH
• lokus kvantitativního znaku genetika   MeSH
• šlechtění rostlin * metody   MeSH
• zemědělské plodiny * genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• genetické markery MeSH

The leaves above the ear serve as a major source of carbohydrates for grain filling in maize. However, increasing the number of leaves above the ear to strengthen the source and improve maize yield remains challenging in modern maize breeding. Here, we clone the causative gene of the quantitative trait locus (QTL) associated with the number of leaves above the ear. The causative gene is the previously reported MADS-box domain-encoding gene Tunicate1 (Tu1), which is responsible for the phenotype of pod corn or Tunicate maize. We show that Tu1 can substantially increase the leaf number above the ear while maintaining the source‒sink balance. A distal upstream 5-base pair (bp) insertion of Tu1 originating from a popcorn landrace enhances its transcription, coregulates its plastochron activators and repressors, and increases the number of leaves above the ear. Field tests demonstrate that the 5-bp insertion of Tu1 can increase grain yields by 11.4% and 9.5% under regular and dense planting conditions, respectively. The discovery of this favorable Tu1 allele from landraces suggests that landraces represent a valuable resource for high-yield breeding of maize.

• MeSH
• alely MeSH
• fenotyp MeSH
• geneticky modifikované rostliny MeSH
• kukuřice setá * genetika   růst a vývoj   metabolismus   MeSH
• listy rostlin * genetika   růst a vývoj   metabolismus   MeSH
• lokus kvantitativního znaku * MeSH
• proteiny domény MADS genetika   metabolismus   MeSH
• regulace genové exprese u rostlin * MeSH
• rostlinné proteiny * genetika   metabolismus   MeSH
• šlechtění rostlin MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• proteiny domény MADS MeSH
• rostlinné proteiny * MeSH

Coevolution of parasites with their hosts may lead to balancing selection on genes involved in determining the specificity of host-parasite interactions, but examples of such specific interactions in wild vertebrates are scarce. Here, we investigated whether the polymorphic outer surface protein C (OspC), used by the Lyme disease agent, Borrelia afzelii, to manipulate vertebrate host innate immunity, interacts with polymorphic major histocompatibility genes (MHC), while concurrently eliciting a strong antibody response, in one of its main hosts in Europe, the bank vole. We found signals of balancing selection acting on OspC, resulting in little differentiation in OspC variant frequencies between years. Neither MHC alleles nor their inferred functional groupings (supertypes) significantly predicted the specificity of infection with strains carrying different OspC variants. However, we found that MHC alleles, but not supertypes, significantly predicted the level of IgG antibodies against two common OspC variants among seropositive individuals. Our results thus indicate that MHC alleles differ in their ability to induce antibody responses against specific OspC variants, which may contribute to selection of OspC polymorphism by the vole immune system.

• Klíčová slova
• bacteria, host parasite interactions, mammals, population genetics—empirical,
• MeSH
• adaptivní imunita * genetika   MeSH
• alely MeSH
• antigeny bakteriální MeSH
• Arvicolinae * genetika   imunologie   mikrobiologie   MeSH
• Borrelia burgdorferi komplex * genetika   imunologie   patogenita   MeSH
• hlavní histokompatibilní komplex * genetika   MeSH
• imunoglobulin G imunologie   MeSH
• lymeská nemoc * imunologie   genetika   mikrobiologie   MeSH
• polymorfismus genetický MeSH
• proteiny vnější bakteriální membrány * genetika   imunologie   MeSH
• protilátky bakteriální krev   imunologie   MeSH
• selekce (genetika) genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny bakteriální MeSH
• imunoglobulin G MeSH
• OspC protein MeSH Prohlížeč
• proteiny vnější bakteriální membrány * MeSH
• protilátky bakteriální MeSH

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10-5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.

• Klíčová slova
• DNA methylation, pancreatic cancer, risk factors, single‐nucleotide polymorphism,
• MeSH
• alely MeSH
• antigeny nádorové * genetika   MeSH
• Asijci genetika   MeSH
• běloši genetika   MeSH
• duktální karcinom pankreatu * genetika   MeSH
• genetická predispozice k nemoci MeSH
• GPI-vázané proteiny * genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokus kvantitativního znaku MeSH
• metylace DNA MeSH
• nádorové proteiny * genetika   MeSH
• nádory slinivky břišní * genetika   MeSH
• studie případů a kontrol MeSH
• vazebná nerovnováha * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové * MeSH
• GPI-vázané proteiny * MeSH
• nádorové proteiny * MeSH
• PSCA protein, human MeSH Prohlížeč

Interspecific introgression is a potentially important source of novel variation of adaptive significance. Although multiple cases of adaptive introgression are well documented, broader generalizations about its targets and mechanisms are lacking. Multiallelic balancing selection, particularly when acting through rare allele advantage, is an evolutionary mechanism expected to favor adaptive introgression. This is because introgressed alleles are likely to confer an immediate selective advantage, facilitating their establishment in the recipient species even in the face of strong genomic barriers to introgression. Vertebrate major histocompatibility complex genes are well-established targets of long-term multiallelic balancing selection, so widespread adaptive major histocompatibility complex introgression is expected. Here, we evaluate this hypothesis using data from 29 hybrid zones formed by fish, amphibians, squamates, turtles, birds, and mammals at advanced stages of speciation. The key prediction of more extensive major histocompatibility complex introgression compared to genome-wide introgression was tested with three complementary statistical approaches. We found evidence for widespread adaptive introgression of major histocompatibility complex genes, providing a link between the process of adaptive introgression and an underlying mechanism. Our work identifies major histocompatibility complex introgression as a general mechanism by which species can acquire novel, and possibly regain previously lost, variation that may enhance defense against pathogens and increase adaptive potential.

• Klíčová slova
• MHC, adaptation, host–pathogen coevolution, hybridization, introgression,
• MeSH
• genová introgrese * MeSH
• hlavní histokompatibilní komplex * genetika   MeSH
• hybridizace genetická * MeSH
• molekulární evoluce MeSH
• obratlovci * genetika   MeSH
• selekce (genetika) MeSH
• vznik druhů (genetika) MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Many enhancers control gene expression by assembling regulatory factor clusters, also referred to as condensates. This process is vital for facilitating enhancer communication and establishing cellular identity. However, how DNA sequence and transcription factor (TF) binding instruct the formation of high regulatory factor environments remains poorly understood. Here we developed a new approach leveraging enhancer-centric chromatin accessibility quantitative trait loci (caQTLs) to nominate regulatory factor clusters genome-wide. By analyzing TF-binding signatures within the context of caQTLs and comparing episomal versus endogenous enhancer activities, we discovered a class of regulators, 'context-only' TFs, that amplify the activity of cell type-specific caQTL-binding TFs, that is, 'context-initiator' TFs. Similar to super-enhancers, enhancers enriched for context-only TF-binding sites display high coactivator binding and sensitivity to bromodomain-inhibiting molecules. We further show that binding sites for context-only and context-initiator TFs underlie enhancer coordination, providing a mechanistic rationale for how a loose TF syntax confers regulatory specificity.

• MeSH
• chromatin * genetika   metabolismus   MeSH
• lidé MeSH
• lokus kvantitativního znaku * MeSH
• myši MeSH
• regulace genové exprese MeSH
• transkripční faktory * metabolismus   genetika   MeSH
• vazba proteinů MeSH
• vazebná místa genetika   MeSH
• zesilovače transkripce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chromatin * MeSH
• transkripční faktory * MeSH

This study highlights the agronomic potential of rare introgressions, as demonstrated by a major QTL for powdery mildew resistance on chromosome 7D. It further shows evidence for inter-homoeologue recombination in wheat. Agriculturally important genes are often introgressed into crops from closely related donor species or landraces. The gene pool of hexaploid bread wheat (Triticum aestivum) is known to contain numerous such "alien" introgressions. Recently established high-quality reference genome sequences allow prediction of the size, frequency and identity of introgressed chromosome regions. Here, we characterise chromosomal introgressions in bread wheat using exome capture data from the WHEALBI collection. We identified 24,981 putative introgression segments of at least 2 Mb across 434 wheat accessions. Detailed study of the most frequent introgressions identified T. timopheevii or its close relatives as a frequent donor species. Importantly, 118 introgressions of at least 10 Mb were exclusive to single wheat accessions, revealing that large populations need to be studied to assess the total diversity of the wheat pangenome. In one case, a 14 Mb introgression in chromosome 7D, exclusive to cultivar Pamukale, was shown by QTL mapping to harbour a recessive powdery mildew resistance gene. We identified multiple events where distal chromosomal segments of one subgenome were duplicated in the genome and replaced the homoeologous segment in another subgenome. We propose that these examples are the results of inter-homoeologue recombination. Our study produced an extensive catalogue of the wheat introgression landscape, providing a resource for wheat breeding. Of note, the finding that the wheat gene pool contains numerous rare, but potentially important introgressions and chromosomal rearrangements has implications for future breeding.

• MeSH
• chromozomy rostlin * genetika   MeSH
• genová introgrese MeSH
• lokus kvantitativního znaku * MeSH
• mapování chromozomů MeSH
• nemoci rostlin genetika   mikrobiologie   MeSH
• odolnost vůči nemocem * genetika   MeSH
• pšenice * genetika   mikrobiologie   MeSH
• rekombinace genetická MeSH
• šlechtění rostlin MeSH
• Publikační typ
• časopisecké články MeSH

Alternative polyadenylation (APA) modulates mRNA processing in the 3'-untranslated regions (3' UTR), affecting mRNA stability and translation efficiency. Research into genetically regulated APA has the potential to provide insights into cancer risk. In this study, we conducted large APA-wide association studies to investigate associations between APA levels and cancer risk. Genetic models were built to predict APA levels in multiple tissues using genotype and RNA sequencing data from 1,337 samples from the Genotype-Tissue Expression project. Associations of genetically predicted APA levels with cancer risk were assessed by applying the prediction models to data from large genome-wide association studies of six common cancers among European ancestry populations: breast, ovarian, prostate, colorectal, lung, and pancreatic cancers. A total of 58 risk genes (corresponding to 76 APA sites) were associated with at least one type of cancer, including 25 genes previously not linked to cancer susceptibility. Of the identified risk APAs, 97.4% and 26.3% were supported by 3'-UTR APA quantitative trait loci and colocalization analyses, respectively. Luciferase reporter assays for four selected putative regulatory 3'-UTR variants demonstrated that the risk alleles of 3'-UTR variants, rs324015 (STAT6), rs2280503 (DIP2B), rs1128450 (FBXO38), and rs145220637 (LDHA), significantly increased the posttranscriptional activities of their target genes compared with reference alleles. Furthermore, knockdown of the target genes confirmed their ability to promote proliferation and migration. Overall, this study provides insights into the role of APA in the genetic susceptibility to common cancers. Significance: Systematic evaluation of associations of alternative polyadenylation with cancer risk reveals 58 putative susceptibility genes, highlighting the contribution of genetically regulated alternative polyadenylation of 3'UTRs to genetic susceptibility to cancer.

• MeSH
• 3' nepřekládaná oblast * genetika   MeSH
• celogenomová asociační studie * MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• lokus kvantitativního znaku MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory * genetika   MeSH
• polyadenylace * MeSH
• regulace genové exprese u nádorů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 3' nepřekládaná oblast * MeSH
• messenger RNA MeSH