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
• Adult MeSH
• Endogenous Retroviruses * genetics   MeSH
• Carcinogenesis * genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   metabolism   MeSH
• Breast Neoplasms * virology   pathology   genetics   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article 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
• Autoimmune Diseases etiology   virology   MeSH
• Endogenous Retroviruses * genetics   metabolism   MeSH
• Genome, Human genetics   MeSH
• Genome, Viral genetics   MeSH
• Virus Integration genetics   MeSH
• Humans MeSH
• Retroviridae Proteins, Oncogenic genetics   metabolism   MeSH
• Retroviridae genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review 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.

• MeSH
• Endogenous Retroviruses * genetics   MeSH
• Animals, Genetically Modified MeSH
• Humans MeSH
• Myelin Sheath MeSH
• Mice MeSH
• Neuroglia MeSH
• Multiple Sclerosis * genetics   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

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
• Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics   MeSH
• Leukemia, Myeloid, Acute genetics   MeSH
• Child MeSH
• DNA, Neoplasm genetics   MeSH
• Adult MeSH
• Transcription, Genetic MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Child, Preschool MeSH
• Gene Expression Regulation, Leukemic MeSH
• Reproducibility of Results MeSH
• Retroelements genetics   MeSH
• Aged MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article 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
• Acyltransferases genetics   MeSH
• Alleles MeSH
• Long Interspersed Nucleotide Elements genetics   MeSH
• Phospholipases A2, Calcium-Independent genetics   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Genotype MeSH
• Liver pathology   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Humans MeSH
• Non-alcoholic Fatty Liver Disease genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Chromosome Breakpoints * MeSH
• Alu Elements * MeSH
• Genomics * methods   MeSH
• Gene Rearrangement * MeSH
• Humans MeSH
• DNA Mutational Analysis methods   MeSH
• Polymerase Chain Reaction * methods   MeSH
• Sequence Deletion MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Research Support, Non-U.S. Gov't 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
• Cricetinae MeSH
• Mesocricetus metabolism   MeSH
• RNA, Small Interfering genetics   MeSH
• Oocytes metabolism   pathology   MeSH
• Retroelements physiology   MeSH
• RNA Helicases genetics   MeSH
• Spermatogenesis genetics   physiology   MeSH
• Spermatogonia metabolism   pathology   MeSH
• Testis metabolism   MeSH
• Gene Silencing physiology   MeSH
• Animals MeSH
• Check Tag
• Cricetinae MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't 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
• Genome Size MeSH
• Gene Duplication MeSH
• Genetic Loci MeSH
• Genome, Plant * MeSH
• Contig Mapping methods   MeSH
• Quantitative Trait, Heritable * MeSH
• Triticum genetics   MeSH
• Gene Expression Regulation, Plant MeSH
• Retroelements MeSH
• Plant Proteins genetics   metabolism   MeSH
• Starch biosynthesis   MeSH
• Plant Breeding MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Crops, Agricultural genetics   MeSH
• Secale genetics   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't 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.

• MeSH
• Algorithms MeSH
• Evolution, Molecular MeSH
• Retroelements * genetics   MeSH
• Software * MeSH
• DNA Transposable Elements MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

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
• Chromosome Deletion MeSH
• Adult MeSH
• Alu Elements genetics   MeSH
• Exons genetics   MeSH
• Glycogen Storage Disease Type IIb diagnosis   genetics   physiopathology   MeSH
• X Chromosome Inactivation genetics   MeSH
• Cardiomyopathies genetics   physiopathology   MeSH
• Cullin Proteins genetics   MeSH
• Humans MeSH
• Lysosomal-Associated Membrane Protein 2 genetics   MeSH
• X-Linked Intellectual Disability genetics   physiopathology   MeSH
• Loss of Function Mutation genetics   MeSH
• Myocardium metabolism   MeSH
• Sodium-Potassium-Exchanging ATPase genetics   MeSH
• Transcription Factors genetics   MeSH
• DNA Copy Number Variations genetics   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH