Cytogenetic and Genome Research最新文献

Correct regulation of cohesin at chromosome arms and centromeres and accurate kinetochore-microtubule connections are significant for proper chromosome segregation. At anaphase of meiosis I, cohesin at chromosome arms is cleaved by separase, leading to the separation of homologous chromosomes. However, at anaphase of meiosis II, cohesin at centromeres is cleaved by separase, leading to the separation of sister chromatids. Shugoshin-2 (SGO2) is a member of the shugoshin/MEI-S332 protein family in mammalian cells, a crucial protein that protects centromeric cohesin from cleavage by separase and corrects wrong kinetochore-microtubule connections before anaphase of meiosis I. Shugoshin-1 (SGO1) plays a similar role in mitosis. Moreover, shugoshin can inhibit the occurrence of chromosomal instability (CIN), and its abnormal expression in several tumors, such as triple-negative breast cancer, hepatocellular carcinoma, lung cancer, colon cancer, glioma, and acute myeloid leukemia, can be used as biomarker for disease progression and potential therapeutic targets for cancers. Thus, this review discusses the specific mechanisms of shugoshin which regulates cohesin, kinetochore-microtubule connections, and CIN.

Brachydactyly mental retardation syndrome (BDMR) typically results from large deletions (>2-9 Mb) in distal 2q37. Haploinsufficiency of HDAC4 with incomplete penetrance has been proposed as the primary genetic cause of BDMR. To date, pure 2q37 deletions distal to HDAC4 were reported only in a limited number of individuals who share a subset of the clinical manifestations seen in cases with 2q37 deletions encompassing HDAC4. Here, we present a 4-year-old African American male who carries the smallest established 2q37.3 deletion distal to HDAC4 (827.1 kb; 16 OMIM genes). His clinical features that overlap with BDMR phenotypes include expressive-receptive language delay, behavioral issues, mild facial dysmorphism such as frontal bossing, and bilateral 5th finger brachydactyly and clinodactyly. The deletion was inherited from his mother with a history of learning difficulties and similar facial dysmorphism. This case provides important genotype-phenotype correlation information and suggests a 2q37 region distal to HDAC4 encompassing the HDLBP gene may contribute to a subset of clinical features overlapping with those seen in individuals with BDMR.

White-bellied Erpornis (Erpornis zantholeuca) is a group of birds in the order Passeriformes, but its taxonomic status remains controversial. To understand the phylogenetic position of E. zantholeuca and phylogenetic relations within this family, we sequenced the complete mitochondrial genome of E. zantholeuca, which was 16,902 bp in length, containing 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a control region. The nucleotide composition of the whole genome was 30.10% A, 30.48% C, 15.14% G, and 24.28% T and showed an elevated AT content (54.38%). All genes were encoded on the H-strand, with the exceptions of 8 tRNAs (trnQ, trnA, trnN, trnC, trnY, trnS2(UCN), trnP, trnE) and 1 PCG (Mt-ND6). Most PCGs used standard ATN as start codons, and TAN as stop codons. All tRNAs were predicted to form the typical cloverleaf secondary structures. The gene order of E. zantholeuca was consistent with that of Gallus gallus, which was considered to be a plesiomorphic or typical avian gene order. Phylogenetic relationships based on bayesian inference and maximum likelihood methods showed that E. zantholeuca was well supported as the sister group of (Vireo altiloquus + Vireo olivaceus). In addition, Pteruthius melanotis was sister to the other members of Vireonidae.

Copy number variants (CNVs) are a common finding in the clinical setting and contribute to both genetic variation and disease. Studies have described the accumulation of multiple CNVs as a disease-modifying mechanism. While it has been described how additional CNVs may play a role in phenotype, in which ways and to what extent sex chromosomes are involved in dual CNV scenario has not been fully defined. To describe the distribution of CNVs, a secondary data analysis using the DECIPHER database on 2,273 de-identified individuals with two CNVs was performed. CNVs were designated larger and secondary based on size and characteristics. We found that the X chromosome was observed to be the most common chromosome involved in secondary CNVs. Further analysis showed CNVs on the sex chromosome have significant differences compared to autosomes when comparing median size (p = 0.013), pathogenicity groups (p < 0.001), and variant classification (p = 0.001). Lastly, we identified chromosome combinations for larger and secondary CNVs and observed the plurality of secondary CNVs fell in the same chromosome as the larger. The observations of this study provide additional information on sex chromosome CNV involvement in a variety of indications.

The family Cervidae is the second most diverse family in the infraorder Pecora and is characterized by a striking variability in the diploid chromosome numbers among species, ranging from 6 to 70. Chromosomal rearrangements in Cervidae have been studied in detail by chromosome painting. There are many comparative cytogenetic data for both subfamilies (Cervinae and Capreolinae) based on homologies with chromosomes of cattle and Chinese muntjac. Previously it was found that interchromosomal rearrangements are the major type of rearrangements occurring in the Cervidae family. Here, we build a detailed chromosome map of a female reindeer (Rangifer tarandus, 2n = 70, Capreolinae) and a female black muntjac (Muntiacus crinifrons, 2n = 8, Cervinae) with dromedary homologies to find out what other types of rearrangements may have underlined the variability of Cervidae karyotypes. To track chromosomal rearrangements and the distribution of nucleolus organizer regions not only during Cervidae but also Pecora evolution, we summarized new data and compared them with chromosomal maps of other already studied species. We discuss changes in the pecoran ancestral karyotype in the light of new painting data. We show that intrachromosomal rearrangements in autosomes of Cervidae are more frequent than previously thought: at least 13 inversions in evolutionary breakpoint regions were detected.

We performed optical genome mapping (OGM), a newly developed cytogenetic technique, for a patient with a disorder of sex development (DSD) and a 46,XX,t(9;11)(p22;p13) karyotype. The results of OGM were validated using other methods. OGM detected a 9;11 reciprocal translocation and successfully mapped its breakpoints to small regions of 0.9-12.3 kb. OGM identified 46 additional small structural variants, only three of which were detected by array-based comparative genomic hybridization. OGM suggested the presence of complex rearrangements on chromosome 10; however, these variants appeared to be artifacts. The 9;11 translocation was unlikely to be associated with DSD, while the pathogenicity of the other structural variants remained unknown. These results indicate that OGM is a powerful tool for detecting and characterizing chromosomal structural variations, although the current methods of OGM data analyses need to be improved.

Advances in "omics" technology have made it possible to study a wide range of cellular phenomena at the single-cell level. Recently, we developed single-cell DNA replication sequencing (scRepli-seq) that measures replication timing (RT) by copy number differences between replicated and unreplicated genomic DNA in replicating single mammalian cells. This method has been used to reveal previously unrecognized static and dynamic natures of several hundred kilobases to a few megabases-scale chromosomal units called RT domains. Because RT domains are highly correlated to A/B compartments detected by Hi-C, scRepli-seq data can be used to predict the 3D organization of the genome in the nuclear space. scRepli-seq, which essentially measures the copy number, can also be applied to study genome instability.

Currently, our knowledge of how different cell types in a tissue microenvironment respond to low and high linear energy transfer (LET) radiation is highly restricted. In this study, a comparative analysis was performed on γ-ray-induced DNA damage and repair in primary human melanocytes and keratinocytes isolated from 3 donors. Our study demonstrates a modest interindividual variability in both melanocytes and keratinocytes in terms of both spontaneous and ionizing radiation (IR)-induced 53BP1 foci formation and persistence. Melanocytes, in general, showed a slightly elevated (1.66-2.79 folds more) 53BP1 foci induction relative to keratinocytes after exposure to different doses of γ-rays (0.1-2.5 Gy) radiation. To verify the influence of ATM kinase on IR-induced 53BP1 foci formation, melanocytes and keratinocytes were treated with a specific ATM kinase inhibitor (KU55993, 10 μM) for 1 h prior to radiation. ATM kinase inhibition resulted in the reduction of both spontaneous and IR-induced 53BP1 foci by 17-42% in both melanocytes and keratinocytes of all the 3 donors. Increased persistence of IR-induced 53BP1 foci number was observed in ATM-inhibited melanocytes and keratinocytes after different post exposure times (6 h and 24 h). Taken together, our study suggests that interindividual variations exist in the induction and repair of DNA double-strand breaks (DSBs) in melanocytes and keratinocytes and that ATM is crucial for an optimal DSB repair efficiency in both human skin cell types.

There are 2 genetically divergent groups in the dojo loach Misgurnus anguillicaudatus: A and B. Although most wild-type diploids reproduce sexually, clonal diploids (clonal loach) reproduce gynogenetically in certain areas. Clonal loaches produce unreduced isogenic eggs by premeiotic endomitosis, and such diploid eggs develop gynogenetically following activation by the sperm of sympatric wild-type diploids. These clonal loaches have presumably arisen from past hybridization events between 2 different ancestors. The genomic differences between these 2 groups have not been completely elucidated. Thus, new genetic and cytogenetic markers are required to distinguish between these 2 groups. Here, we compared the 5S rDNA region to develop markers for the identification of different dojo loach groups. The nontranscribed sequence (NTS) of the 5S rDNA was highly polymorphic and group-specific. NTSs were found in clades of 2 different groups in clonal loaches. In contrast, we did not find any group-specific sequences in the coding region of the 5S rRNA gene. Sequences were located near the centromere of the short arm of the largest submetacentric chromosomes in groups A and B and clonal loaches. Thus, the 5S rDNA of the dojo loach is conserved at the chromosomal location. Whereas, the sequences of the NTS regions evolved group-specifically in the dojo loach, with the sequences of both groups being conserved in clonal loaches.

Mitotic chromosomes of butterflies, which look like dots or short filaments in most published data, are generally considered to lack localised centromeres and thus to be holokinetic. This particularity, observed in a number of other invertebrates, is associated with meiotic particularities known as "inverted meiosis," in which the first division is equational, i.e., centromere splitting-up and segregation of sister chromatids instead of homologous chromosomes. However, the accurate analysis of butterfly chromosomes is difficult because (1) their size is very small, equivalent to 2 bands of a mammalian metaphase chromosome, and (2) they lack satellite DNA/heterochromatin in putative centromere regions and therefore marked primary constrictions. Our improved conditions for basic chromosome preparations, here applied to 6 butterfly species belonging to families Nymphalidae and Pieridae challenges the holocentricity of their chromosomes: in spite of the absence of primary constrictions, sister chromatids are recurrently held together at definite positions during mitotic metaphase, which makes possible to establish karyotypes composed of acrocentric and submetacentric chromosomes. The total number of chromosomes per karyotype is roughly inversely proportional to that of non-acrocentric chromosomes, which suggests the occurrence of frequent robertsonian-like fusions or fissions during evolution. Furthermore, the behaviour and morphological changes of chromosomes along the various phases of meiosis do not seem to differ much from those of canonical meiosis. In particular, at metaphase II chromosomes clearly have 2 sister chromatids, which refutes that anaphase I was equational. Thus, we propose an alternative mechanism to holocentricity for explaining the large variations in chromosome numbers in butterflies: (1) in the ancestral karyotype, composed of about 62 mostly acrocentric chromosomes, the centromeres, devoid of centromeric heterochromatin/satellite DNA, were located at contact with telomeric heterochromatin; (2) the instability of telomeric heterochromatin largely contributed to drive the multiple rearrangements, principally chromosome fusions, which occurred during butterfly evolution.