INTRODUCTION: Breast cancer is the most common cancer and the leading cause of cancer death in women. Recent research indicates that human endogenous retroviruses (HERVs) may be linked to carcinogenesis, but the data remain controversial. METHODS: HERVs' expression was evaluated to show the differences between breast cancer and control samples, and their associations with clinicopathological parameters. Gene expression of 12 HERVs, i.e., ERVE-4, ERVW-1, ERVFRD-1, ERVV-1, ERV3-1, ERVH48-1, ERVMER34-1, ERVK-7, ERVK13-1, ERVK11-1, ERVK3-1, and HCP5, was analyzed by qPCR and/or TCGA datasets for breast cancer. RESULTS: ERV3-1, ERVFRD-1, ERVH48-1, and ERVW-1 provided data to support their tumor suppressor roles in breast cancer. ERV3-1 evinced the best performing diagnostic data based on qPCR, i.e. , AUC: 0.819 (p < 0.0001), sensitivity of 72.41%, and specificity of 89.66%. Lower levels of ERV3-1 were noted in advanced stage and higher grades, and significant negative association was found in relation to Ki-67 levels. Oncogenic roles may be inferred for ERVK13-1, ERVV-1, and ERVMER34-1. Data for ERVK-7, ERVE-4, ERVK11-1, and HCP5 remain inconclusive. CONCLUSION: Differential HERV expression may be applicable to evaluate novel biomarkers for breast cancer. However, more research is needed to reveal their real clinical impact, the biological roles, and regulatory mechanisms in breast carcinogenesis.
- MeSH
- dospělí MeSH
- endogenní retroviry * genetika MeSH
- karcinogeneze * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory prsu * virologie patologie genetika MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Endogénne retrovírusy (ERV) sú genetické elementy, ktoré boli integrované do genómu hostiteľa pred viac ako 100 miliónmi rokov. Ich integrácia prebehla v zárodočných bunkách, čím sa v ľudskej populácii zabezpečil ich prenos z generácie na generáciu. V súčasnosti sa predpokladá, že tvoria až 8 % ľudského genómu. V priebehu evolúcie došlo v endogénnych retrovírusoch ku hromadeniu rôznych mutácii, čo viedlo k ich znefunkčneniu, a preto sa v minulosti považovali za odpadovú DNA. V posledných rokoch sa však ukazuje, že nie sú úplne nefunkčné. S pribúdajúcimi analýzami ľudského genómu sa odhaľujú ich potenciálne úlohy aj v ľudskom organizme.
Endogenous retroviruses (ERVs) are genetic elements that were integrated into the host genome more than 100 million years ago. Their integration took place in germ cells, ensuring their vertical transmission in the human population. They are currently thought to make up to 8 % of the human genome. During evolution, various mutations have accumulated in endogenous retroviruses, leading to their dysfunction, and were therefore considered as junk DNA in the past. However, in recent years it has turned out that they are not completely dysfunctional. With more data becoming available from human genome analyses, their potential roles in the human body are being revealed.
- MeSH
- autoimunitní nemoci etiologie virologie MeSH
- endogenní retroviry * genetika metabolismus MeSH
- genom lidský genetika MeSH
- genom virový genetika MeSH
- integrace viru genetika MeSH
- lidé MeSH
- Retroviridae - proteiny onkogenní genetika metabolismus MeSH
- Retroviridae genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The human endogenous retrovirus type W (HERV-W) has been identified and repeatedly confirmed as human-specific pathogenic entity affecting many cell types in multiple sclerosis (MS). Our recent contributions revealed the encoded envelope (ENV) protein to disturb myelin repair by interfering with oligodendroglial precursor differentiation and by polarizing microglial cells toward an axon-damage phenotype. Indirect proof of ENV's antiregenerative and degenerative activities has been gathered recently in clinical trials using a neutralizing anti-ENV therapeutic antibody. Yet direct proof of its mode of action can only be presented here based on transgenic ENV expression in mice. Upon demyelination, we observed myelin repair deficits, neurotoxic microglia and astroglia, and increased axon degeneration. Experimental autoimmune encephalomyelitis activity progressed faster in mutant mice equally accompanied by activated glial cells. This study therefore provides direct evidence on HERV-W ENV's contribution to the overall negative impact of this activated viral entity in MS.
Retroelements (RE) have been proposed as important players in cancerogenesis. Different cancer types are characterized by a different level of tumor-specific RE insertions. In previous studies, small cohorts of hematological malignancies, such as acute myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia have been characterized by a low level of RE insertional activity. Acute lymphoblastic leukemia (ALL) in adults and childhood acute leukemias have not been studied in this context. We performed a search for new RE insertions (Alu and L1) in 44 childhood ALL, 14 childhood acute myeloid leukemia, and 14 adult ALL samples using a highly sensitive NGS-based approach. First, we evaluated the method sensitivity revealing the 1% detection threshold for the proportion of cells with specific RE insertion. Following this result, we did not identify new tumor-specific RE insertions in the tested cohort of acute leukemia samples at the established level of sensitivity. Additionally, we analyzed the transcription levels of active L1 copies and found them increased. Thus, the increased transcription of active L1 copies is not sufficient for overt elevation of L1 retrotranspositional activity in leukemia.
- MeSH
- akutní lymfatická leukemie genetika MeSH
- akutní myeloidní leukemie genetika MeSH
- dítě MeSH
- DNA nádorová genetika MeSH
- dospělí MeSH
- genetická transkripce MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- regulace genové exprese u leukemie MeSH
- reprodukovatelnost výsledků MeSH
- retroelementy genetika MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The patatin-like phospholipase domain containing 3 (PNPLA3) gene (viz. its I148M variant) is one of the key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We have identified a novel insertion/deletion variant of 1114 bp, localized in the second intron of the PNPLA3 gene, which corresponds to the 3' terminal sequence of the long-interspersed element (LINE-1). DNA analysis of 122 NAFLD patients and 167 control subjects as well as RNA analysis of 19 liver biopsies revealed that the novel variant is very common (frequency = 0.41), fully linked to the clinically important I148M variant, and clinically silent. Although the LINE-1 insertion does not seem to have any biological effect, it can impede genotyping of the I148M variant. If insertion prevents the attachment of the diagnostic primer, then the non-insertion allele will be selectively amplified; and thus the frequency of the 148M "risk" allele will be significantly overestimated due to the complete linkage of the LINE-1 insertion and the 148I allele of the PNPLA3 gene. Therefore, our findings underline the importance of careful design and consistent documentation of the methodology, including primer sequences. Critical revisions of the results of some studies that have already been reported may therefore be needed.
- MeSH
- acyltransferasy genetika MeSH
- alely MeSH
- dlouhé rozptýlené jaderné elementy genetika MeSH
- fosfolipasy A2 nezávislé na vápníku genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genotyp MeSH
- játra patologie MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- nealkoholová steatóza jater genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PIWI-interacting RNAs (piRNAs) support the germline by suppressing retrotransposons. Studies of the pathway in mice have strongly shaped the view that mammalian piRNAs are essential for male but not for female fertility. Here, we report that the role of the piRNA pathway substantially differs in golden hamsters (Mesocricetus auratus), the piRNA pathway setup of which more closely resembles that of other mammals, including humans. The loss of the Mov10l1 RNA helicase-an essential piRNA biogenesis factor-leads to striking phenotypes in both sexes. In contrast to mice, female Mov10l1-/- hamsters are sterile because their oocytes do not sustain zygotic development. Furthermore, Mov10l1-/- male hamsters have impaired establishment of spermatogonia accompanied by transcriptome dysregulation and an expression surge of a young retrotransposon subfamily. Our results show that the mammalian piRNA pathway has essential roles in both sexes and its adaptive nature allows it to manage emerging genomic threats and acquire new critical roles in the germline.
- MeSH
- křečci praví MeSH
- křeček rodu Mesocricetus metabolismus MeSH
- malá interferující RNA genetika MeSH
- oocyty metabolismus patologie MeSH
- retroelementy fyziologie MeSH
- RNA-helikasy genetika MeSH
- spermatogeneze genetika fyziologie MeSH
- spermatogonie metabolismus patologie MeSH
- testis metabolismus MeSH
- umlčování genů fyziologie MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Rye is a valuable food and forage crop, an important genetic resource for wheat and triticale improvement and an indispensable material for efficient comparative genomic studies in grasses. Here, we sequenced the genome of Weining rye, an elite Chinese rye variety. The assembled contigs (7.74 Gb) accounted for 98.47% of the estimated genome size (7.86 Gb), with 93.67% of the contigs (7.25 Gb) assigned to seven chromosomes. Repetitive elements constituted 90.31% of the assembled genome. Compared to previously sequenced Triticeae genomes, Daniela, Sumaya and Sumana retrotransposons showed strong expansion in rye. Further analyses of the Weining assembly shed new light on genome-wide gene duplications and their impact on starch biosynthesis genes, physical organization of complex prolamin loci, gene expression features underlying early heading trait and putative domestication-associated chromosomal regions and loci in rye. This genome sequence promises to accelerate genomic and breeding studies in rye and related cereal crops.
- MeSH
- délka genomu MeSH
- duplikace genu MeSH
- genetické lokusy MeSH
- genom rostlinný * MeSH
- kontigové mapování metody MeSH
- kvantitativní znak dědičný * MeSH
- pšenice genetika MeSH
- regulace genové exprese u rostlin MeSH
- retroelementy MeSH
- rostlinné proteiny genetika metabolismus MeSH
- škrob biosyntéza MeSH
- šlechtění rostlin MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- zemědělské plodiny genetika MeSH
- žito genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
MOTIVATION: Transposable elements (TEs) in eukaryotes often get inserted into one another, forming sequences that become a complex mixture of full-length elements and their fragments. The reconstruction of full-length elements and the order in which they have been inserted is important for genome and transposon evolution studies. However, the accumulation of mutations and genome rearrangements over evolutionary time makes this process error-prone and decreases the efficiency of software aiming to recover all nested full-length TEs. RESULTS: We created software that uses a greedy recursive algorithm to mine increasingly fragmented copies of full-length LTR retrotransposons in assembled genomes and other sequence data. The software called TE-greedy-nester considers not only sequence similarity but also the structure of elements. This new tool was tested on a set of natural and synthetic sequences and its accuracy was compared to similar software. We found TE-greedy-nester to be superior in a number of parameters, namely computation time and full-length TE recovery in highly nested regions. AVAILABILITY AND IMPLEMENTATION: http://gitlab.fi.muni.cz/lexa/nested. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Cullin 4B (CUL4B), lysosomal-associated membrane protein Type 2 (LAMP2), ATP1B4, TMEM255A, and ZBTB33 are neighboring genes on Xq24. Mutations in CUL4B result in Cabezas syndrome (CS). Male CS patients present with dysmorphic, neuropsychiatric, genitourinary, and endocrine abnormalities. Heterozygous CS females are clinically asymptomatic. LAMP2 mutations cause Danon disease (DD). Cardiomyopathy is a dominant feature of DD present in both males and heterozygous females. No monogenic phenotypes have been associated with mutations in ATP1B4, TMEM255A, and ZBTB33 genes. To facilitate diagnostics and counseling in CS and DD families, we present a female DD patient with a de novo Alu-mediated Xq24 rearrangement causing a deletion encompassing CUL4B, LAMP2, and also the other three neighboring genes. Typical to females heterozygous for CUL4B mutations, the patient was CS asymptomatic, however, presented with extremely skewed X-chromosome inactivation (XCI) ratios in peripheral white blood cells. As a result of the likely selection against CUL4B deficient clones, only minimal populations (~3%) of LAMP2 deficient leukocytes were identified by flow cytometry. On the contrary, myocardial LAMP2 protein expression suggested random XCI. We demonstrate that contiguous CUL4B and LAMP2 loss-of-function copy number variations occur and speculate that male patients carrying similar defects could present with features of both CS and DD.
- MeSH
- chromozomální delece MeSH
- dospělí MeSH
- elementy Alu genetika MeSH
- exony genetika MeSH
- glykogenóza typu IIb diagnóza genetika patofyziologie MeSH
- inaktivace chromozomu X genetika MeSH
- kardiomyopatie genetika patofyziologie MeSH
- kulinové proteiny genetika MeSH
- lidé MeSH
- membránový protein 2 asociovaný s lyzozomy genetika MeSH
- mentální retardace vázaná na chromozom X genetika patofyziologie MeSH
- mutace ztráty funkce genetika MeSH
- myokard metabolismus MeSH
- sodíko-draslíková ATPasa genetika MeSH
- transkripční faktory genetika MeSH
- variabilita počtu kopií segmentů DNA genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
