Chromosomal inversions occur in natural populations of many species, and may underlie reproductive isolation and local adaptation. Traditional methods of inversion discovery are labor-intensive and lack sensitivity. Here, we report the use of three-dimensional contact probabilities between genomic loci as assayed by chromosome-conformation capture sequencing (Hi-C) to detect multi-megabase polymorphic inversions in four barley genotypes. Inversions are validated by fluorescence in situ hybridization and Bionano optical mapping. We propose Hi-C as a generally applicable method for inversion discovery in natural populations.

• Klíčová slova
• Hordeum vulgare, barley, chromosomal inversions, chromosome conformation capture sequencing, genomics, optical mapping, technical advance,
• MeSH
• chromozomální inverze genetika   MeSH
• chromozomy rostlin genetika   MeSH
• genom rostlinný genetika   MeSH
• genotyp MeSH
• hybridizace in situ fluorescenční MeSH
• ječmen (rod) genetika   MeSH
• mapování chromozomů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Human chromosome inversions are types of balanced structural variations, making them difficult to analyze. Thanks to PEM (paired-end sequencing and mapping), there has been tremendous progress in studying inversions. Inversions play an important role as an evolutionary factor, contributing to the formation of gonosomes, speciation of chimpanzees and humans, and inv17q21.3 or inv8p23.1 exhibit the features of natural selection. Both inversions have been related to pathogenic phenotype by directly affecting a gene structure (e.g., inv5p15.1q14.1), regulating gene expression (e.g., inv7q21.3q35) and by predisposing to other secondary arrangements (e.g., inv7q11.23). A polymorphism of human inversions is documented by the InvFEST database (a database that stores information about clinical predictions, validations, frequency of inversions, etc.), but only a small fraction of these inversions is validated, and a detailed analysis is complicated by the frequent location of breakpoints within regions of repetitive sequences.

• Klíčová slova
• cytogenetics, disease, evolution, human chromosome, inversion, polymorphism,
• MeSH
• chromozomální inverze genetika   MeSH
• chromozomy MeSH
• lidé MeSH
• lidské chromozomy MeSH
• molekulární evoluce * MeSH
• polymorfismus genetický * MeSH
• repetitivní sekvence nukleových kyselin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Recent advances in sequencing allow population-genomic data to be generated for virtually any species. However, approaches to analyse such data lag behind the ability to generate it, particularly in nonmodel species. Linkage disequilibrium (LD, the nonrandom association of alleles from different loci) is a highly sensitive indicator of many evolutionary phenomena including chromosomal inversions, local adaptation and geographical structure. Here, we present linkage disequilibrium network analysis (LDna), which accesses information on LD shared between multiple loci genomewide. In LD networks, vertices represent loci, and connections between vertices represent the LD between them. We analysed such networks in two test cases: a new restriction-site-associated DNA sequence (RAD-seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well-characterized single nucleotide polymorphism (SNP) data set from 21 three-spined stickleback individuals. In each case, we readily identified five distinct LD network clusters (single-outlier clusters, SOCs), each comprising many loci connected by high LD. In A. baimaii, further population-genetic analyses supported the inference that each SOC corresponds to a large inversion, consistent with previous cytological studies. For sticklebacks, we inferred that each SOC was associated with a distinct evolutionary phenomenon: two chromosomal inversions, local adaptation, population-demographic history and geographic structure. LDna is thus a useful exploratory tool, able to give a global overview of LD associated with diverse evolutionary phenomena and identify loci potentially involved. LDna does not require a linkage map or reference genome, so it is applicable to any population-genomic data set, making it especially valuable for nonmodel species.

• Klíčová slova
• Anopheles dirus, Anopheles gambiae, chromosomal rearrangement, graph theory, landscape genomics, r package,
• MeSH
• Anopheles klasifikace   genetika   MeSH
• chromozomální inverze * MeSH
• jednonukleotidový polymorfismus MeSH
• molekulární evoluce MeSH
• populační genetika metody   MeSH
• sekvenční analýza DNA MeSH
• shluková analýza MeSH
• Smegmamorpha klasifikace   genetika   MeSH
• vazebná nerovnováha * MeSH
• výpočetní biologie metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

Chromosomal inversions have been identified in many natural populations and can be responsible for novel traits and rapid adaptation. In zebra finch, a large region on the Z chromosome has been subject to multiple inversions, which have pleiotropic effects on multiple traits but especially on sperm phenotypes, such as midpiece and flagellum length. To understand the effect, the Z inversion has on these traits, we examined testis and liver transcriptomes of young males at different maturation times. We compared gene expression differences among three inversion karyotypes: AA, B*B* and AB*, where B* denotes the inverted regions on Z with respect to A. In testis, 794 differentially expressed genes were found and most of them were located on chromosome Z. They were functionally enriched for sperm-related traits. We also identified clusters of co-expressed genes that matched with the inversion-related sperm phenotypes. In liver, there were some enriched functions and some overrepresentation on chromosome Z with similar location as in testis. In both tissues, the overrepresented genes were located near the distal end of Z but also in the middle of the chromosome. For the heterokaryotype, we observed several genes with one allele being dominantly expressed, similar to expression patterns in one or the other homokaryotype. This was confirmed with SNPs for three genes, and interestingly one gene, DMGDH, had allele-specific expression originating mainly from one inversion haplotype in the testis, yet both inversion haplotypes were expressed equally in the liver. This karyotype-specific difference in tissue-specific expression suggests a pleiotropic effect of the inversion and thus suggests a mechanism for divergent phenotypic effects resulting from an inversion.

• Klíčová slova
• Taeniopygia guttata, chromosome inversion, liver, testis, transcriptomics,
• MeSH
• chromozomální inverze * genetika   MeSH
• exprese genu genetika   MeSH
• fenotyp MeSH
• játra * metabolismus   MeSH
• karyotyp MeSH
• pěnkavovití * genetika   MeSH
• pohlavní chromozomy genetika   MeSH
• spermie metabolismus   MeSH
• testis * metabolismus   MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The incidence of paracentric inversions in the general population has not been clearly established, it ranges from 0.09 to 0.49/1,000. Homologue pairing during melosis in a paracentric-inversion heterozygote is maximized by the formation of an inversion loop. If a crossing-over occurs within this loop, dicentric and acentric chromosomes are formed. Resulting gametes can have variety of duplications and deficiencies and give a non-viable progeny. One of the exceptions to the rule is a mutation event "U loop recombination". From U-loop event a monocentric recombinant chromosome can arise by an abnormal process, which involves chromatid breakage and reunion. Most of the paracentric inversions in man are harmless and the risk of heterozygotes having a child with an unbalanced karyotype is relatively low. In carriers of an accidentally discovered paracentric inversion, amniocentesis is optional. However, in some cases, it is difficult to distinguish between a paracentric inversion and paracentric insertion--the risk of the insertion is about 15%. When a de novo inversion is detected in amniotic fluid, the overall risk for two-break rearrangements is 6.7%.

• MeSH
• chromozomální inverze * MeSH
• gametogeneze MeSH
• karyotypizace MeSH
• lidé MeSH
• rekombinace genetická MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

Pericentric inversions of human chromosomes represent rearrangements are formed between two breaks on the short and on long arms of the chromosome with following rotation and new connection of the separated segment in the reversed position. The abnormality does not result in most of the carriers to any clinical manifestations. However, the basic risk the carriers of such inversion are exposed is the possibility of formation of a recombinant aneusomy--later transformation of the inverted chromosome during gametogenesis. Conception by the recombinant gamete usually results in spontaneous abortion or to a birth of seriously affected individual. The risk of recombination has to be in every newly registered inversion individually considered. The larger part of chromosome is taken into the pericentic inversion, the smaller is the extent of resulting duplication and smaller is the deficiency of chromosomal parts, which results from the recombination. The higher is then the viability of the affected foetus. In families with detected recombination, chromosomal examination is fully recommended. Prenatal examination is also indicated when the transformation is listed among the risk inversions or it has larger extent then recorded inversions. Beside the risk inversions, also the "safe" inversions exist, which include minor and frequently occurring transformation of chromosome No 2--inv(2)(p11q13) and inversion of chromosome 10--inv(10)(p11q21).

• MeSH
• chromozomální aberace genetika   MeSH
• chromozomální inverze * MeSH
• chromozomální poruchy MeSH
• heterozygot * MeSH
• lidé MeSH
• prenatální diagnóza MeSH
• rekombinace genetická MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

In many species, polymorphic genomic inversions underlie complex phenotypic polymorphisms and facilitate local adaptation in the face of gene flow. Multiple polymorphic inversions can co-occur in a genome, but the prevalence, evolutionary significance, and limits to complexity of genomic inversion landscapes remain poorly understood. Here, we examine genome-wide genetic variation in one of Europe's most destructive forest pests, the spruce bark beetle Ips typographus, scan for polymorphic inversions, and test whether inversions are associated with key traits in this species. We analyzed 240 individuals from 18 populations across the species' European range and, using a whole-genome resequencing approach, identified 27 polymorphic inversions covering ∼28% of the genome. The inversions vary in size and in levels of intra-inversion recombination, are highly polymorphic across the species range, and often overlap, forming a complex genomic architecture. We found no support for mechanisms such as directional selection, overdominance, and associative overdominance that are often invoked to explain the presence of large inversion polymorphisms in the genome. This suggests that inversions are either neutral or maintained by the combined action of multiple evolutionary forces. We also found that inversions are enriched in odorant receptor genes encoding elements of recognition pathways for host plants, mates, and symbiotic fungi. Our results indicate that the genome of this major forest pest of growing social, political, and economic importance harbors one of the most complex inversion landscapes described to date and raise questions about the limits of intraspecific genomic architecture complexity.

• Klíčová slova
• Ips typographus, forest pest, genome complexity, polymorphic inversions, spruce bark beetle,
• MeSH
• brouci genetika   MeSH
• chromozomální inverze * MeSH
• genom hmyzu * MeSH
• lesy MeSH
• polymorfismus genetický * MeSH
• receptory pachové genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• receptory pachové MeSH

The study aimed to investigate prevalent chromosomal breakpoints identified in balanced structural chromosomal anomalies and to pinpoint potential candidate genes linked with male infertility. This was acchieved through a comprehensive approach combining RNA-seq and microarray data analysis, enabling precise identification of candidate genes. The Cytogenetics data from 2,500 infertile males referred to Royan Research Institute between 2009 and 2022 were analyzed, with 391 cases meeting the inclusion criteria of balanced chromosomal rearrangement. Of these, 193 cases exhibited normal variations and were excluded from the analysis. By examining the breakpoints, potential candidate genes were suggested. Among the remaining 198 cases, reciprocal translocations were the most frequent anomaly (129 cases), followed by Robertsonian translocations (43 cases), inversions (34 cases), and insertions (3 cases).Some patients had more than one chromosomal abnormality. Chromosomal anomalies were most frequently observed in chromosomes 13 (21.1%), 14 (20.1%), and 1 (16.3%) with 13q12, 14q12, and 1p36.3 being the most prevalent breakpoints, respectively. Chromosome 1 contributed the most to reciprocal translocations (20.2%) and inversions (17.6%), while chromosome 14 was the most involved in the Robertsonian translocations (82.2%). The findings suggested that breakpoints at 1p36.3 and 14q12 might be associated with pregestational infertility, whereas breakpoints at 13q12 could be linked to both gestational and pregestational infertility. Several candidate genes located on common breakpoints were proposed as potentially involved in male infertility. Bioinformatics analyses utilizing three databases were conducted to examine the expression patterns of 78 candidate genes implicated in various causes of infertility.‏ In azoospermic individuals, significant differential expression was observed in 19 genes: 15 were downregulated (TSSK2, SPINK2, TSSK4, CDY1, CFAP70, BPY2, BTG4, FKBP6, PPP2R1B, SPECC1L, CENPJ, ‏SKA3, FGF9, NODAL, CLOCK), while four genes were upregulated ‏(‏HSPB1, MIF, PRF1, ENTPD6). In the case of Asthenozoospermia, seven genes showed significant upregulation (PRF1, DDX21, KIT, SRD5A3, MTCH1, DDX50, NODAL). Though RNA-seq data for Teratozoospermia were unavailable, microarray data revealed differential expression insix genes: three downregulated (BUB1, KLK4, PIWIL2) and three upregulated (AURKC, NPM2, RANBP2). These findings enhance our understanding of the molecular basis of male infertility and could provide valuable insights for future diagnostic and therapeutic strategies.

• Klíčová slova
• Balanced chromosomal abnormality, Breakpoint, Male infertility, Pregestational/gestational infertility,
• MeSH
• body zlomu chromozomu MeSH
• chromozomální aberace MeSH
• cytogenetické vyšetření MeSH
• lidé MeSH
• mužská infertilita * genetika   MeSH
• translokace genetická * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Three mouse models of male-limited, hybrid-type sterility are available: the sterility controlled by the T-t genetic complex, the hybrid sterility system including the Hst-1 gene, and the sterility of carriers of various chromosomal anomalies. A large body of experimental evidence has been gathered on the nonrandom attraction between X chromosome and rearranged autosomes in meiosis of carriers of various male-sterile chromosomal rearrangements in mice and men. A hypothesis is evaluated relating the X-autosomal interaction to spermatogenic breakdown. New data on the structure of t haplotypes indicate the presence of chromosomal inversions, and this might point to a chromosomal type of sterility of tx/ty hybrids. Gene hybrid sterility-1 is responsible for different fertility of male hybrids between certain laboratory and wild mice. The availability of wild mice (Mus musculus) derived inbred strains PWB, PWD, and PWK may facilitate further study of the hybrid sterility phenomenon in the mouse.

• MeSH
• chromozom X MeSH
• chromozomální aberace genetika   MeSH
• chromozomální poruchy MeSH
• divoká zvířata genetika   MeSH
• geny recesivní MeSH
• hybridizace genetická MeSH
• letální geny MeSH
• meióza MeSH
• mutantní kmeny myší genetika   MeSH
• mužská infertilita etiologie   genetika   MeSH
• myši MeSH
• spermatogeneze MeSH
• translokace genetická MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Nijmegen breakage syndrome (NBS) is an autosomal recessive chromosomal instability disorder with hypersensitivity to ionising radiation. The clinical phenotype is characterised by congenital microcephaly, mild dysmorphic facial appearance, growth retardation, immunodeficiency, and greatly increased risk for lymphoreticular malignancy. Most NBS patients are of Slavic origin and homozygous for the founder mutation 657del5. The frequency of 657del5 heterozygotes in the Czech population is 1:150. Recently, another NBS1 mutation, 643C>T(R215W), with uncertain pathogenicity was found to have higher frequency among tumour patients of Slavic origin than in controls. This alteration results in the substitution of the basic amino acid arginine with the non-polar tryptophan and thus could potentially interfere with the function of the NBS1 protein, nibrin. METHODS AND RESULTS: Children with congenital microcephaly are routinely tested for the 657del5 mutation in the Czech and Slovak Republics. Here, we describe for the first time a severe form of NBS without chromosomal instability in monozygotic twin brothers with profound congenital microcephaly and developmental delay who are compound heterozygotes for the 657del5 and 643C>T(R215W) NBS1 mutations. Both children showed reduced expression of full length nibrin when compared with a control and a heterozygote for the 657del5 mutation. Radiation response processes such as phosphorylation of ATM and phosphorylation/stabilisation of p53, which are promoted by NBS1, are strongly reduced in cells from these patients. CONCLUSIONS: Interestingly, the patients are more severely affected than classical NBS patients. Consequently, we postulate that homozygosity for the 643C>T(R215W) mutation will also lead to a, possibly very, severe disease phenotype.

• MeSH
• chromozomální nestabilita MeSH
• fosforylace MeSH
• geny recesivní MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• mapování chromozomů * MeSH
• mikrocefalie genetika   MeSH
• mutace * MeSH
• nemoci u dvojčat MeSH
• polymerázová řetězová reakce MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• substituce aminokyselin MeSH
• syndrom Nijmegen breakage genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• jaderné proteiny MeSH
• NBN protein, human MeSH Prohlížeč
• proteiny buněčného cyklu MeSH