• MeSH
• lidé MeSH
• lidský chromozom Y * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cieľ štúdie: Zavedenie metódy DNA analýzy AZF (Azoospermia factor region) oblasti Y chromozómu u mužov s poruchami plodnosti v Slovenskej republike. Typ štúdie: Genetická-prospektívna štúdia. Názov a sídlo pracoviska: Ústav lekárskej biológie, genetiky a klinickej genetiky LFUK a FNsP, Bratislava. Metodika: Detekcia bola robená pomocou polymerázovej reťazovej reakcie, použitím troch rôznych sád sY sekvencií. Na overenie niektorých typov delécií bol použitý fluorescenčne značený diagnostický set. Výsledky: Súbor tvorilo 822 mužov, z nich 349 s azoospermiou a 473 s oligospermiou. Delécie v AZF oblasti Y chromozómu boli potvrdené v 38 prípadoch (4,62 %). Z nich je 24 (6,88 %) pacientov zo súboru s azoospermiou a 14 zo súboru pacientov s oligospermiou (2,95 %). Zaznamenali sme delécie v každej z podoblastí AZF (a, b, c), kombinovanú AZFbc deléciu, ale aj deléciu celej AZF oblasti. Záver: Štúdia potvrdila, že detekcia mikrodelécii AZF oblasti má diagnostický a prognostický význam a poukázala na dôležitosť selekčných kritérií výberu pacientov.

Objective: Study on Y chromosomal AZF region deletions in Slovak population, application of DNA technique. Design: Genetic-prospective study. Setting: Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava. Methods: For detecting microdeletions in the Y-chromosomal AZF region in men with fertility disorders and for identifying Y-specific sequences we used the method of polymerase chain reaction (PCR) with using three different sets of sY sequences. For a verification of the specific type of deletion we used also fluorescently labeled kit. Results: Diagnoses of referred patients were divided into 2 groups: azoospermia, oligospermia. In the followed-up group of 822 patients there were 349 patients with azoospermia, 473 patients with oligospermia. Globally we reported 38 cases of deletions in the AZF region of the Y chromosome, i.e. 4.62%. 24 patients with deletion are from the group of patients with azoospermia, i.e. 6.88%, 14 patients are from the group of patients with oligospermia (2.95%). Considering particular types of deletions we recorded deletions in each region, AZFa, AZFb and AZFc, combinated AZFbc deletion, but also a complete deletion of the whole AZF region. Conclusion: The study confirmed that detection of microdeletions of the AZF region is significant from diagnostic and prognostic view and it pointed out the importance of selection criteria for selecting patients.

• MeSH
• azoospermie genetika   MeSH
• chromozomální delece MeSH
• dospělí MeSH
• lidé genetika   MeSH
• lidský chromozom Y genetika   MeSH
• mužská infertilita genetika   MeSH
• oligospermie genetika   MeSH
• polymerázová řetězová reakce MeSH
• proteiny semenné plazmy genetika   MeSH
• sekvenční analýza DNA MeSH
• Check Tag
• dospělí MeSH
• lidé genetika   MeSH
• mužské pohlaví MeSH

Aims. The Y chromosome accumulates male-related genes including sex-determining region of Y-chromosome (SRY) and several spermatogenesis-related genes. The long arm contains azoospermia factor (AZF) region (including sub-regions AZFa, AZFb and AZFc). Microdeletions in this region are responsible for azoospermia and oligospermia and result in the male infertility. The aim of this study was to analyze incidence of microdeletions in the AZF region of Y chromosome in patients with azoospermia from Slovakia. Patients and Methods. Over the period from 2005 to 2009 a total of 239 men (mean age 31.74 years) were analyzed. The diagnosis of azoospermia was established on the basis of semen analysis. All patient samples were analyzed cytogenetically. Chromosomal analysis was performed on all patients on cultured lymphocytes from peripheral blood. For exact diagnosis of microdeletions in AZF region we used a PCR-method using a set of sequence-tagged sites from all AZF sub-regions (according to the recommendation by the European Academy of Andrology and the European Quality Monitoring Network Group). Results. Among our 226 patients with azoospermia and with normal karyotype, 8 patients (mean age 30.6 years) had microdeletions in the AZF region of the Y chromosome (3.35%). Considering particular types of deletions we determined deletions in each region AZFa,b,c but also a complete deletion of the entire AZF region. The presence of microdeletion(s) in the AZFc region was the most frequent. In our study we found 12 patients (5%) with 47,XXY karyotype (Klinefelter syndrome), but these patients didn't have microdeletion of Y chromosomes. Conclusion. The study confirmed that percentage of microdeletions in the AZF region is low in Slovak azoospermic patients, but important from a prognostic view.

• MeSH
• azoospermie genetika   MeSH
• chromozomální delece MeSH
• dospělí MeSH
• lidé MeSH
• lidský chromozom Y genetika   MeSH
• proteiny semenné plazmy genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Geografické názvy
• Slovenská republika MeSH

Pathogenic variants affecting the BLM gene are responsible for the manifestation of extremely rare cancer‐predisposing Bloom syndrome. The present study reports on a case of an infant with a congenital hypotrophy, short stature and abnormal facial appearance. Initially she was examined using a routine molecular diagnostic algorithm, including the cytogenetic analysis of her karyotype, microarray analysis and methylation‐specific MLPA, however, she remained undiagnosed on a molecular level. Therefore, she and her parents were enrolled in the project of trio‐based exome sequencing (ES) using Human Core Exome kit. She was revealed as a carrier of an extremely rare combination of causative sequence variants altering the BLM gene (NM_000057.4), c.1642C>T and c.2207_2212delinsTAGATTC in the compound heterozygosity, resulting in a diagnosis of Bloom syndrome. Simultaneously, a mosaic loss of heterozygosity of chromosome 11p was detected and then confirmed as a borderline imprinting center 1 hypermethylation on chromosome 11p15. The diagnosis of Bloom syndrome and mosaic copy‐number neutral loss of heterozygosity of chromosome 11p increases a lifetime risk to develop any types of malignancy. This case demonstrates the trio‐based ES as a complex approach for the molecular diagnostics of rare pediatric diseases.

• MeSH
• Bloomův syndrom * diagnóza   genetika   patologie   MeSH
• dítě MeSH
• heterozygot MeSH
• kojenec MeSH
• lidé MeSH
• lidský chromozom Y MeSH
• mozaicismus MeSH
• sekvenování exomu MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Over the past two decades numerous new trees of modern human populations have been published extensively but little attention has been paid to formal phylogenetic synthesis. We utilized the "matrix representation with parsimony" (MRP) method to infer a composite phylogeny (supertree) of modern human populations, based on 257 genetic/genomic, as well as linguistic, phylogenetic trees and 44 admixture plots from 200 published studies (1990-2014). The resulting supertree topology includes the most basal position of S African Khoisan followed by C African Pygmies, and the paraphyletic section of all other sub-Saharan peoples. The sub-Saharan African section is basal to the monophyletic clade consisting of the N African-W Eurasian assemblage and the consistently monophyletic Eastern superclade (Sahul-Oceanian, E Asian, and Beringian-American peoples). This topology, dominated by genetic data, is well-resolved and robust to parameter set changes, with a few unstable areas (e.g., West Eurasia, Sahul-Melanesia) reflecting the existing phylogenetic controversies. A few populations were identified as highly unstable "wildcard taxa" (e.g. Andamanese, Malagasy). The linguistic classification fits rather poorly on the supertree topology, supporting a view that direct coevolution between genes and languages is far from universal.

• MeSH
• algoritmy MeSH
• dějiny starověku MeSH
• fylogeneze * MeSH
• lidé MeSH
• lidský chromozom Y genetika   MeSH
• lingvistika MeSH
• mitochondriální DNA genetika   MeSH
• populační genetika dějiny   MeSH
• sekvenování celého genomu MeSH
• Check Tag
• dějiny starověku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• subsaharská Afrika MeSH

The Maniq and Mlabri are the only recorded nomadic hunter-gatherer groups in Thailand. Here, we sequenced complete mitochondrial (mt) DNA genomes and ~2.364 Mbp of non-recombining Y chromosome (NRY) to learn more about the origins of these two enigmatic populations. Both groups exhibited low genetic diversity compared to other Thai populations, and contrasting patterns of mtDNA and NRY diversity: there was greater mtDNA diversity in the Maniq than in the Mlabri, while the converse was true for the NRY. We found basal uniparental lineages in the Maniq, namely mtDNA haplogroups M21a, R21 and M17a, and NRY haplogroup K. Overall, the Maniq are genetically similar to other negrito groups in Southeast Asia. By contrast, the Mlabri haplogroups (B5a1b1 for mtDNA and O1b1a1a1b and O1b1a1a1b1a1 for the NRY) are common lineages in Southeast Asian non-negrito groups, and overall the Mlabri are genetically similar to their linguistic relatives (Htin and Khmu) and other groups from northeastern Thailand. In agreement with previous studies of the Mlabri, our results indicate that the Malbri do not directly descend from the indigenous negritos. Instead, they likely have a recent origin (within the past 1,000 years) by an extreme founder event (involving just one maternal and two paternal lineages) from an agricultural group, most likely the Htin or a closely-related group.

• MeSH
• Asijci genetika   MeSH
• genetická variace * MeSH
• haplotypy MeSH
• lidé MeSH
• lidský chromozom Y * MeSH
• mitochondriální DNA chemie   genetika   MeSH
• osoby s přechodným pobytem a migranti * MeSH
• sekvenční analýza DNA MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Thajsko MeSH

Complex chromosomal rearrangements (CCR) represent rare structural chromosome abnormalities frequently associated with infertility. In this study, meiotic segregation in spermatozoa of an infertile normospermic carrier of a 4-breakpoint t(1;3;6) CCR was analysed. A newly developed array comparative genomic hybridization protocol was used, and all chromosomes in 50 single sperm cells were simultaneously examined. Three-colour FISH was used to analyse chromosome segregation in 1557 other single sperm cells. It was also used to measure an interchromosomal effect; sperm chromatin structure assay was used to measure chromatin integrity. A high-frequency of unbalanced spermatozoa (84%) was observed, mostly arising from the 3:3 symmetrical segregation mode. Array comparative genomic hybridization was used to detect additional aneuploidies in two out of 50 spermatozoa (4%) in chromosomes not involved in the complex chromosome rearrangement. Significantly increased rates of diploidy and XY disomy were found in the CCR carrier compared with the control group (P < 0.001). Defective condensation of sperm chromatin was also found in 22.7% of spermatozoa by sperm chromatin structure assay. The results indicate that the infertility in the man with CCR and normal spermatozoa was caused by a production of chromosomally unbalanced, XY disomic and diploid spermatozoa and spermatozoa with defective chromatin condensation.

• MeSH
• analýza jednotlivých buněk MeSH
• body zlomu chromozomu * MeSH
• dospělí MeSH
• genová přestavba * MeSH
• heterozygot MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• mužská infertilita etiologie   MeSH
• poruchy sexuálního vývoje s karyotypem 46, XY diagnóza   genetika   patologie   patofyziologie   MeSH
• profáze meiózy I MeSH
• segregace chromozomů * MeSH
• spermie patologie   MeSH
• srovnávací genomová hybridizace MeSH
• translokace genetická * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Today, African pastoralists are found mainly in the Sahel/Savannah belt spanning 6,000 km from west to east, flanked by the Sahara to the north and tropical rainforests to the south. The most significant group among them are the Fulani who not only keep cattle breeds of possible West Eurasian ancestry, but form themselves a gene pool containing some paternally and maternally-transmitted West Eurasian haplogroups. MATERIALS AND METHODS: We generated complete sequences for 33 mitogenomes belonging to haplogroups H1 and U5 (23 and 10, respectively), and genotyped 16 STRs in 65 Y chromosomes belonging to haplogroup R1b-V88. RESULTS: We show that age estimates of the maternal lineage H1cb1, occurring almost exclusively in the Fulani, point to the time when the first cattle herders settled the Sahel/Savannah belt. Similar age estimates were obtained for paternal lineage R1b-V88, which occurs today in the Fulani but also in other, mostly pastoral populations. Maternal clade U5b1b1b, reported earlier in the Berbers, shows a shallower age, suggesting another possibly independent input into the Sahelian pastoralist gene pool. CONCLUSIONS: Despite the fact that animal domestication originated in the Near East ∼ 10 ka, and that it was from there that animals such as sheep, goats as well as cattle were introduced into Northeast Africa soon thereafter, contemporary cattle keepers in the Sahel/Savannah belt show uniparental genetic affinities that suggest the possibility of an ancient contact with an additional ancestral population of western Mediterranean ancestry.

• MeSH
• antropologie fyzická MeSH
• černoši genetika   MeSH
• dějiny starověku MeSH
• fylogeneze MeSH
• haplotypy genetika   MeSH
• lidé MeSH
• lidský chromozom Y genetika   MeSH
• migrace lidstva dějiny   MeSH
• mitochondriální DNA genetika   MeSH
• populační genetika MeSH
• zemědělství dějiny   MeSH
• Check Tag
• dějiny starověku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• subsaharská Afrika MeSH

BACKGROUND: Tick-borne encephalitis (TBE) is the main tick-borne viral infection in Eurasia. Its manifestations range from inapparent infections and fevers with complete recovery to debilitating or fatal encephalitis. The basis of this heterogeneity is largely unknown, but part of this variation is likely due to host genetic. We have previously found that BALB/c mice exhibit intermediate susceptibility to the infection of TBE virus (TBEV), STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, carrying 12.5% of the STS genome on the background of the BALB/c genome is even more susceptible than BALB/c. Importantly, mouse orthologs of human TBE controlling genes Oas1b, Cd209, Tlr3, Ccr5, Ifnl3 and Il10, are in CcS-11 localized on segments derived from the strain BALB/c, so they are identical in BALB/c and CcS-11. As they cannot be responsible for the phenotypic difference of the two strains, we searched for the responsible STS-derived gene-locus. Of course the STS-derived genes in CcS-11 may operate through regulating or epigenetically modifying these non-polymorphic genes of BALB/c origin. METHODS: To determine the location of the STS genes responsible for susceptibility of CcS-11, we analyzed survival of TBEV-infected F2 hybrids between BALB/c and CcS-11. CcS-11 carries STS-derived segments on eight chromosomes. These were genotyped in the F2 hybrid mice and their linkage with survival was tested by binary trait interval mapping. We have sequenced genomes of BALB/c and STS using next generation sequencing and performed bioinformatics analysis of the chromosomal segment exhibiting linkage with TBEV survival. RESULTS: Linkage analysis revealed a novel suggestive survival-controlling locus on chromosome 7 linked to marker D7Nds5 (44.2 Mb). Analysis of this locus for polymorphisms between BALB/c and STS that change RNA stability and genes' functions led to detection of 9 potential candidate genes: Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3. One of them, Cd33, carried a nonsense mutation in the STS strain. CONCLUSIONS: The robust genetic system of recombinant congenic strains of mice enabled detection of a novel suggestive locus on chromosome 7. This locus contains 9 candidate genes, which will be focus of future studies not only in mice but also in humans.

• MeSH
• ABC transportéry genetika   MeSH
• genotyp MeSH
• lidé MeSH
• lidské chromozomy, pár 7 genetika   MeSH
• mapování chromozomů * MeSH
• myši MeSH
• transportní proteiny genetika   MeSH
• virové nemoci mortalita   MeSH
• viry klíšťové encefalitidy patogenita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

INTRODUCTION: Next-generation sequencing is now used on a routine basis for molecular testing but studies on copy-number variant (CNV) detection from next-generation sequencing data are underrepresented. Utilizing an existing whole-exome sequencing (WES) dataset, we sought to investigate the contribution of rare CNVs to the genetic causality of dystonia. METHODS: The CNV read-depth analysis tool ExomeDepth was applied to the exome sequences of 953 unrelated patients with dystonia (600 with isolated dystonia and 353 with combined dystonia; 33% with additional neurological involvement). We prioritized rare CNVs that affected known disease genes and/or were known to be associated with defined microdeletion/microduplication syndromes. Pathogenicity assessment of CNVs was based on recently published standards of the American College of Medical Genetics and Genomics and the Clinical Genome Resource. RESULTS: We identified pathogenic or likely pathogenic CNVs in 14 of 953 patients (1.5%). Of the 14 different CNVs, 12 were deletions and 2 were duplications, ranging in predicted size from 124bp to 17 Mb. Within the deletion intervals, BRPF1, CHD8, DJ1, EFTUD2, FGF14, GCH1, PANK2, SGCE, UBE3A, VPS16, WARS2, and WDR45 were determined as the most clinically relevant genes. The duplications involved chromosomal regions 6q21-q22 and 15q11-q13. CNV analysis increased the diagnostic yield in the total cohort from 18.4% to 19.8%, as compared to the assessment of single-nucleotide variants and small insertions and deletions alone. CONCLUSIONS: WES-based CNV analysis in dystonia is feasible, increases the diagnostic yield, and should be combined with the assessment of single-nucleotide variants and small insertions and deletions.

• MeSH
• dospělí MeSH
• dystonické poruchy diagnóza   genetika   MeSH
• dystonie diagnóza   genetika   MeSH
• kohortové studie MeSH
• lidé MeSH
• sekvenování exomu * 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
• práce podpořená grantem MeSH