Aim: Human induced pluripotent stem cells (iPSCs) are inefficiently derived from somatic cells by overexpression of defined transcription factors. Overexpression of H2A histone variant macroH2A1.1, but not macroH2A1.2, leads to increased iPSC reprogramming by unclear mechanisms. Materials & methods: Cleavage under targets and tagmentation (CUT&Tag) allows robust epigenomic profiling of a low cell number. We performed an integrative CUT&Tag-RNA-Seq analysis of macroH2A1-dependent orchestration of iPSCs reprogramming using human endothelial cells. Results: We demonstrate wider genome occupancy, predicted transcription factors binding, and gene expression regulated by macroH2A1.1 during reprogramming, compared to macroH2A1.2. MacroH2A1.1, previously associated with neurodegenerative pathologies, specifically activated ectoderm/neural processes. Conclusion: CUT&Tag and RNA-Seq data integration is a powerful tool to investigate the epigenetic mechanisms occurring during cell reprogramming.

• Klíčová slova
• CUT&Tag, iPSCs, induced pluripotent stem cells, macroH2A1, reprogramming, somatic cells,
• MeSH
• endoteliální buňky metabolismus   MeSH
• histony * metabolismus   MeSH
• indukované pluripotentní kmenové buňky * metabolismus   MeSH
• lidé MeSH
• přeprogramování buněk genetika   MeSH
• sekvenování transkriptomu MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histony * MeSH
• transkripční faktory MeSH

AIM: The aim of this study was to evaluate TSPY (testis specific protein on the Y chromosome) gene and 5'UTR (UnTranslated Region) polymorphisms in men with impaired fertility compared to fertile controls. METHODS: We analyzed 72 infertile men and 31 fertile controls usingconventional sequencing analysis to find crucial SNPs (single nucleotide polymorphism) and other changes. RESULTS: The most remarkable changes were found in the 1(st) exon only. In one half of the both infertile men and fertile controls, the most frequent finding was 26 SNPs with a similar pattern. In the other half we found highly relevant changes, generating a stop codon in the first third of exon 1. Early termination cut down the protein by 78.5%. This kind of change was not found in the fertile controls. No correlation was found between the spermiogram and the changes leading to the stop codon. The distribution of men with deletions, insertion and higher gene copy number was not statistically different. CONCLUSION: The changes found in exon 1 in infertile men could fundamentally affect the process of spermatogenesis. These findings could significantly enhance our understanding of the molecular-genetic causes of male infertility.

• MeSH
• 5' nepřekládaná oblast genetika   MeSH
• dospělí MeSH
• exony genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• lidský chromozom Y genetika   MeSH
• mužská infertilita genetika   MeSH
• počet spermií MeSH
• polymerázová řetězová reakce MeSH
• proteiny buněčného cyklu genetika   MeSH
• sekvenční analýza DNA MeSH
• sekvenční analýza proteinů MeSH
• terminační kodon genetika   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 5' nepřekládaná oblast MeSH
• proteiny buněčného cyklu MeSH
• terminační kodon MeSH
• TSPY1 protein, human MeSH Prohlížeč

Nonspecific structural chromosomal aberrations (CAs) can be found at around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. The frequency of CAs has been measured in occupational monitoring and an increased frequency of CAs has also been associated with cancer risk. Alterations in DNA damage repair and telomere maintenance are thought to contribute to the formation of CAs, which include chromosome type of aberrations and chromatid type of aberrations. In the present study, we used the result of our published genome-wide association studies to extract data on 153 DNA repair genes from 866 nonsmoking persons who had no known occupational exposure to genotoxic substances. Considering an arbitrary cut-off level of P< 5 × 10-3, single nucleotide polymorphisms (SNPs) tagging 22 DNA repair genes were significantly associated with CAs and they remained significant at P < 0.05 when adjustment for multiple comparisons was done by the Binomial Sequential Goodness of Fit test. Nucleotide excision repair pathway genes showed most associations with 6 genes. Among the associated genes were several in which mutations manifest CA phenotype, including Fanconi anemia, WRN, BLM and genes that are important in maintaining genome stability, as well as PARP2 and mismatch repair genes. RPA2 and RPA3 may participate in telomere maintenance through the synthesis of the C strand of telomeres. Errors in NHEJ1 function may lead to translocations. The present results show associations with some genes with known CA phenotype and suggest other pathways with mechanistic rationale for the formation of CAs in healthy nonsmoking population.

• Klíčová slova
• Association study, Chromosomal aberrations, DNA repair, Double-strand breaks,
• MeSH
• běloši genetika   MeSH
• celogenomová asociační studie MeSH
• chromozomální aberace * MeSH
• DNA vazebné proteiny genetika   MeSH
• dospělí MeSH
• enzymy opravy DNA genetika   MeSH
• helikasy RecQ genetika   MeSH
• helikáza Wernerova syndromu genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nekuřáci * MeSH
• oprava chybného párování bází DNA genetika   MeSH
• oprava DNA genetika   MeSH
• počítačová simulace MeSH
• poly(ADP-ribosa)polymerasy genetika   MeSH
• replikační protein A genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH
• Názvy látek
• Bloom syndrome protein MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• enzymy opravy DNA MeSH
• helikasy RecQ MeSH
• helikáza Wernerova syndromu MeSH
• NHEJ1 protein, human MeSH Prohlížeč
• PARP2 protein, human MeSH Prohlížeč
• poly(ADP-ribosa)polymerasy MeSH
• replikační protein A MeSH
• RPA2 protein, human MeSH Prohlížeč
• RPA3 protein, human MeSH Prohlížeč
• WRN protein, human MeSH Prohlížeč

Association mapping of the central part of porcine chromosome 2 harboring QTLs for carcass and meat quality traits was performed with 17 gene-tagged SNPs located between 44.0 and 77.5 Mb on a physical map (Sscrofa10.2) in Italian Large White pigs. For the analyzed animals records of estimated breeding values for average daily gain, back fat thickness, lean cuts, ham weight, feed conversion ratio, pH1, pHu, CIE L*, CIE a*, CIE b* and drip loss were available. A significant QTL for fat deposition (adjusted P=0.0081) and pH1 (adjusted P=0.0972) to MYOD1 at position 44.4 Mb and a QTL for growth and meatiness (adjusted P=0.0238-0.0601) to UBL5 at position 68.9 Mb were mapped. These results from association mapping are much more accurate than those from linkage mapping and facilitate further search for position candidate genes and causative mutations needed for application of markers through marker assisted selection.

• MeSH
• chov MeSH
• fenotyp MeSH
• jednonukleotidový polymorfismus MeSH
• koncentrace vodíkových iontů MeSH
• kvalita jídla * MeSH
• lokus kvantitativního znaku * MeSH
• mapování chromozomů metody   MeSH
• maso analýza   MeSH
• MyoD Protein genetika   MeSH
• prasata genetika   MeSH
• tělesná hmotnost MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• MyoD Protein MeSH
• MyoD1 myogenic differentiation protein MeSH Prohlížeč