The identification of genes of agronomic interest in bread wheat (Triticum aestivum L.) is hampered by its allopolyploid nature (2n = 6x = 42; AABBDD) and its very large genome, which is largely covered by transposable elements. However, owing to this complex structure, aneuploid stocks can be developed in which fragments or entire chromosomes are missing, sometimes resulting in visible phenotypes that help in the cloning of affected genes. In this study, the 2C gametocidal chromosome from Aegilops cylindrica was used to develop a set of 113 deletion lines for chromosome 3D in the reference cultivar Chinese Spring. Eighty-four markers were used to show that the deletions evenly covered chromosome 3D and ranged from 6.5 to 357 Mb. Cytogenetic analyses confirmed that the physical size of the deletions correlated well with the known molecular size deduced from the reference sequence. This new genetic stock will be useful for positional cloning of genes on chromosome 3D, especially for Ph2 affecting homoeologous pairing in bread wheat.

• Klíčová slova
• Ph2, deletion line, gametocidal, homoeologous pairing, wheat,
• Publikační typ
• časopisecké články MeSH

Jacobsen syndrome (JBS) is a rare chromosomal disorder caused by terminal deletion of the long arm of chromosome 11. We report on four prenatally diagnosed patients with JBS with variable prenatal and postnatal phenotypes and 11q deletions of varying sizes. Precise characterization of the deleted region in three patients was performed by SNP arrays. The severity of both the prenatal and postnatal phenotypes did not correlate with the size of the haploinsufficient region. Despite the large difference in the deletion size (nearly 6 Mb), both of the live-born patients had similar phenotypes corresponding to JBS. However, one of the most prominent features of JBS, thrombocytopenia, was only present in the live-born boy. The girl, who had a significantly longer deletion spanning all four genes suspected of being causative of JBS-related thrombocytopenia (FLI1, ETS1, NFRKB, and JAM3), did not manifest a platelet phenotype. Therefore, our findings do not support the traditional view of deletion size correlation in JBS or the causative role of FLI1, ETS1, NFRKB, and JAM3 deletion per se for the development of disease-related thrombocytopenia.

• MeSH
• chromozomální delece * MeSH
• dospělí MeSH
• fenotyp MeSH
• genetické asociační studie MeSH
• Jacobsenův syndrom genetika   patofyziologie   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kojenec MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• mladý dospělý MeSH
• protoonkogenní protein c-fli-1 genetika   MeSH
• trombocytopenie genetika   MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• FLI1 protein, human MeSH Prohlížeč
• protoonkogenní protein c-fli-1 MeSH

LeishGEM is a genome-wide functional annotation community resource for Leishmania mexicana, where deletion mutant growth in vitro and in vivo is measured and protein localisation is determined by endogenous tagging and LOPIT-DC (localisation of organelle proteins by isotope tagging with differential centrifugation) spatial proteomics. Data are being made available pre-publication via http://leishgem.org which allows data-driven identification of the mechanisms for Leishmania parasitism.

• Klíčová slova
• LOPIT-DC, Leishmania, community resource, gene deletion screen, protein tagging,
• MeSH
• delece genu MeSH
• genetická zdatnost MeSH
• genom protozoální * genetika   MeSH
• Leishmania mexicana genetika   metabolismus   MeSH
• Leishmania genetika   metabolismus   MeSH
• proteomika MeSH
• protozoální proteiny * genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• protozoální proteiny * MeSH

PURPOSE: 22q11.2 deletion syndrome (22q11.2DS) is a primary immunodeficiency characterized chiefly by the hypoplasia of the thymus resulting in T cell lymphopenia, increased susceptibility to infections, and higher risk of autoimmune diseases. The irregular thymic niche of T cell development may contribute to autoimmune and atopic complications, whereas the compensatory mechanism of homeostatic T cell proliferation and continuous immune stimulation may result in T cell senescence and exhaustion, further aggravating the immune system dysregulation. METHODS: We used flow cytometry to investigate T cell maturation, delineation, proliferation, activation, and expression of senescence and exhaustion-associated markers (PD1, KLRG1, CD57) in 17 pediatric and adolescent patients with 22q11.2DS and age-matched healthy donors. RESULTS: 22q11.2DS patients aged 0-5 years had fewer naïve but more effector memory T cells with a tendency to approach normal values with increasing age. Young patients in particular had a higher percentage of proliferating T cells and increased expression of PD1, KLRG1, and CD57, as well as cells co-expressing several exhaustion-associated molecules (PD1, KLRG1, Tbet, Eomes, Helios). Additionally, high-risk 22q11.2DS patients with very low numbers of CD4 T cells had significantly higher percentage of Th1 and Th17 T cells, driven in part by higher proportion of mature T cell forms. CONCLUSION: The low thymic output and accelerated T cell differentiation remain the principal features of 22q11.2DS patient immunity, especially in young patients of < 5 years. Later in life, homeostatic proliferation drives expression of T cell exhaustion and senescence-associated markers, suggesting functional aberrations in addition to numeric T cell deficiency.

• Klíčová slova
• 22q11.2 deletion syndrome, CD57, DiGeorge syndrome, PD1, T cells, differentiation, immunodeficiency, maturation, thymus,
• MeSH
• buněčná diferenciace MeSH
• buňky Th17 MeSH
• CD4-pozitivní T-lymfocyty MeSH
• DiGeorgeův syndrom * genetika   MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• počet lymfocytů MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Positional cloning in bread wheat (Triticum aestivum L.) remains a daunting task because of its large genome, high density of repeats, low recombination rate especially in pericentromeric regions and its allopolyploidy. One way to face this challenge is to decrease the size of the interval bearing the gene of interest both genetically and physically, in order to reduce significantly the number of potential candidate genes. In this chapter, we describe a technical approach to produce chromosome-specific deletion lines to locate precisely genes of interest onto wheat chromosomes, a step forward to their cloning.

• Klíčová slova
• Deletion line, Gametocidal, Homeologs, Triticum aestivum, Wheat,
• MeSH
• chléb * MeSH
• chromozomy MeSH
• pšenice * genetika   MeSH
• Publikační typ
• časopisecké články MeSH

Papillary thyroid cancer (PTC) derived from follicular cells is a frequent thyroid tumor. The incidence of this type of malignancy is still growing worldwide. Several major genetic causes are recognized to cause PTC-mutations in the BRAF and RAS genes or rearrangements with the RET proto-oncogene. The most common genetic change found in PTC is a V600E mutation in the BRAF gene presented in 36-69 % of all PTC cases. For routine purposes, several methods were developed to selectively detect only this mutation. However, these methods miss other mutations in the BRAF gene located elsewhere. We focused on the analysis of the exon 15 of the BRAF gene by next-generation sequencing. Here we report a three nucleotide deletion VK600-1E in one patient and present this finding in the context of 13 previously described PTC cases with this deletion. Our patient is the second youngest one among the reported cases. Clinical features of PTC patients with VK600-1E are summarized. For the future, it is important to evaluate genotype-phenotype characteristics of patients with rare BRAF mutations and to follow up them for years.

• Klíčová slova
• BRAF gene, Deletion, Papillary thyroid cancer, Rare mutation,
• MeSH
• dospělí MeSH
• karcinom genetika   MeSH
• lidé MeSH
• nádory štítné žlázy genetika   MeSH
• papilární karcinom štítné žlázy MeSH
• papilární karcinom MeSH
• protoonkogen Mas MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• sekvenční delece MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• MAS1 protein, human MeSH Prohlížeč
• protoonkogen Mas MeSH
• protoonkogenní proteiny B-Raf MeSH

Deletion 20q is a recurrent abnormality in myeloid malignancies. In our previous study, we identified fusion of the additional sex combs-like 1 (ASXL1) and teashirt zinc finger homeobox 2 genes in a patient with myelodysplastic syndrome. The objective of this study was to determine the frequency of ASXL1 breakpoints in a cohort of 36 patients with deletion 20q as the sole cytogenetic aberration. A combination of molecular cytogenetic methods was used to confirm ASXL1 gene alterations in 19 of the 36 patients, and the determination of ASXL1 gene changes in patients with deletion 20q revealed clinical and prognostic impacts.

• MeSH
• chromozomální delece * MeSH
• cytogenetické vyšetření MeSH
• lidé MeSH
• lidské chromozomy, pár 20 genetika   MeSH
• myelodysplastické syndromy genetika   MeSH
• represorové proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ASXL1 protein, human MeSH Prohlížeč
• represorové proteiny MeSH

Chromosomal band 17q12 is a gene-rich region flanked by segmental duplications, making the region prone to deletions and duplications via the non-allelic homologous recombination mechanism. While deletions cause a well-described disorder with a specific phenotype called renal cysts and diabetes mellitus, the phenotype caused by reciprocal duplications is less specific, primarily because of variable expressivity, and incomplete penetrance. We present an unusual family with four children carrying the 17q12 microduplication inherited from their clinically healthy mother, who was a carrier of both the duplication and, interestingly, also of an atypical deletion of the 17q12 region. The duplication was inherited from her diabetic father and the deletion from her diabetic mother who also suffered from a renal disorder. Clinical manifestations in the family were variable, but all children showed some degree of a neurodevelopmental disorder, such as epilepsy, intellectual disability, delayed speech development, or attention deficit disorder. The simultaneous occurrence of a deletion and duplication in the same chromosomal region in one family is very rare, and to our knowledge, individuals carrying both a deletion and a duplication of this region have never been described.

• Klíčová slova
• 17q12 deletion, 17q12 duplication, LHX1 gene, epilepsy, intellectual disability,
• MeSH
• chromozomální delece MeSH
• duplikace chromozomů genetika   MeSH
• fenotyp MeSH
• lidé MeSH
• mentální retardace * genetika   MeSH
• mnohočetné abnormality * genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Background Females with Turner syndrome (TS) are prone to develop autoimmune diseases (AIDs). The X chromosome contains several immune-related genes. Growth hormone (GH) and estrogens modulate the immune system. We aimed to clarify whether the loss of a specific X chromosome gene locus and the administration of GH and estradiol facilitate the development of AIDs in TS females. Methods Retrospective data on clinical course, AIDs, karyotype and treatment were analyzed from a cohort of 286 Czech females with TS (current age 2.8-43.3 years; median age 18.7 years). The karyotypes were sorted using two different classification systems: a mosaicism-focused and an isochromosome (isoXq)-focused approach. Karyotype subgroups with a significantly higher prevalence of AIDs were further evaluated. Data of common therapies were correlated with the prevalence of AIDs. Results The most frequent AIDs were autoimmune thyroid disease (AITD; 37.4%; n = 107) and celiac disease (CD; 8.7%; n = 25). All karyotype subgroups were prone to develop AIDs. Females with an isolated Xp deletion had a significantly higher prevalence of AITD and CD compared to all other individuals with TS (AITD: 66.0% vs. 31.5%, p < 0.0001; CD: 17.4% vs. 7.2%; p = 0.04, respectively). We observed no link between the mean age at initiation as well as the duration of GH and/or estrogen administration and the occurrence of AIDs. Conclusions Isolated Xp deletion contributes to the development of AIDs in TS patients. The haploinsufficiency of genes located in Xpter-p11.2 may explain this observation. Common therapies used in TS do not modify the risk of AIDs.

• Klíčová slova
• Turner syndrome, autoimmune thyroid disease, celiac disease, genetics, isolated Xp deletion, karyotype,
• MeSH
• autoimunitní nemoci epidemiologie   etiologie   MeSH
• chromozomální delece * MeSH
• dítě MeSH
• dospělí MeSH
• karyotypizace MeSH
• lidé MeSH
• lidské chromozomy X genetika   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• předškolní dítě MeSH
• prevalence MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• Turnerův syndrom komplikace   genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

BACKGROUND: Anaplastic oligodendrogliomas (AO) are rare tumors. Two phase III clinical trials (RTOG 9402 and EORTC 26951) proved favorable effects of radiotherapy (RT) with chemotherapy (procarbazine, lomustine and vincristine; PCV) in patients with AO carrying chromosomal mutation of co-deletion1p/19q even if it was not the primary endpoint of these studies. We assessed 1p/19q co-deletion as a prognostic and predictive biomarker for our patients with AO. MATERIALS AND METHODS: 1p/19q co-deletion was assessed by fluorescence in situ hybridization in tumor samples from 23 patients and correlated with progression-free (PFS) and overall (OS) survival for the entire cohort and for the subgroups of patients with different treatment (neurosurgery plus RT alone vs. RT plus PCV). RESULTS: 1p/19q co-deletion was identified in 12 out of 23 tumors (52.2%). Patients with co-deletion had longer OS (587 vs. 132 weeks, p=0.012) and a trend for longer PFS (321 vs. 43 weeks, p=0.075). Patients with co-deletion treated with neurosurgery and RT plus PCV vs. neurosurgery and RT alone also had longer OS (706 vs. 423 weeks, p=0.008). There was no survival difference for patients without 1p/19q co-deletion in relation to treatment. CONCLUSION: The prognostic value of 1p/19q co-deletion in our patients with AO was verified. The strong positive predictive value of this biomarker for OS was also shown for patients with co-deletion treated with neurosurgery and RT plus PCV vs. neurosurgery and RT alone.

• Klíčová slova
• 1p/19q co-deletion, anaplastic oligodendroglioma, predictive biomarker, prognostic biomarker,
• MeSH
• biologické markery metabolismus   MeSH
• chromozomální delece MeSH
• lidé MeSH
• lidské chromozomy, pár 1 genetika   metabolismus   MeSH
• lidské chromozomy, pár 19 genetika   metabolismus   MeSH
• nádory mozku farmakoterapie   MeSH
• oligodendrogliom farmakoterapie   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• biologické markery MeSH