Showing papers on "Chromosome published in 2010"

A three-dimensional model of the yeast genome

Abstract: Layered on top of information conveyed by DNA sequence and chromatin are higher order structures that encompass portions of chromosomes, entire chromosomes, and even whole genomes. Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations. Disparate DNA elements co-localize into functionally defined aggregates or 'factories' for transcription and DNA replication. In budding yeast, Drosophila and many other eukaryotes, chromosomes adopt a Rabl configuration, with arms extending from centromeres adjacent to the spindle pole body to telomeres that abut the nuclear envelope. Nonetheless, the topologies and spatial relationships of chromosomes remain poorly understood. Here we developed a method to globally capture intra- and inter-chromosomal interactions, and applied it to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae. The map recapitulates known features of genome organization, thereby validating the method, and identifies new features. Extensive regional and higher order folding of individual chromosomes is observed. Chromosome XII exhibits a striking conformation that implicates the nucleolus as a formidable barrier to interaction between DNA sequences at either end. Inter-chromosomal contacts are anchored by centromeres and include interactions among transfer RNA genes, among origins of early DNA replication and among sites where chromosomal breakpoints occur. Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome.

Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project

Abstract: We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.

The chromosome number of man

Abstract: While staying last summer at the Sloan-Kettering Institute, New York, one of us tried out some modifications of Hsu’s technique (1952) on various human tissue cultures carried in serial in vitro cultivation at that institute. The results were promising inasmuch as some fairly satisfactory chromosome analyses were obtained in cultures both of tissues of normal origin and of tumours (Levan, 1956).

Haploid plants produced by centromere-mediated genome elimination.

Abstract: Production of haploid plants that inherit chromosomes from only one parent can greatly accelerate plant breeding. Haploids generated from a heterozygous individual and converted to diploid create instant homozygous lines, bypassing generations of inbreeding. Two methods are generally used to produce haploids. First, cultured gametophyte cells may be regenerated into haploid plants, but many species and genotypes are recalcitrant to this process. Second, haploids can be induced from rare interspecific crosses, in which one parental genome is eliminated after fertilization. The molecular basis for genome elimination is not understood, but one theory posits that centromeres from the two parent species interact unequally with the mitotic spindle, causing selective chromosome loss. Here we show that haploid Arabidopsis thaliana plants can be easily generated through seeds by manipulating a single centromere protein, the centromere-specific histone CENH3 (called CENP-A in human). When cenh3 null mutants expressing altered CENH3 proteins are crossed to wild type, chromosomes from the mutant are eliminated, producing haploid progeny. Haploids are spontaneously converted into fertile diploids through meiotic non-reduction, allowing their genotype to be perpetuated. Maternal and paternal haploids can be generated through reciprocal crosses. We have also exploited centromere-mediated genome elimination to convert a natural tetraploid Arabidopsis into a diploid, reducing its ploidy to simplify breeding. As CENH3 is universal in eukaryotes, our method may be extended to produce haploids in any plant species.

Mitotic chromosomal instability and cancer: mouse modelling of the human disease

Abstract: The stepwise progression from an early dysplastic lesion to full-blown metastatic malignancy is associated with increases in genomic instability. Mitotic chromosomal instability - the inability to faithfully segregate equal chromosome complements to two daughter cells during mitosis - is a widespread phenomenon in solid tumours that is thought to serve as the fuel for tumorigenic progression. How chromosome instability (CIN) arises in tumours and what consequences it has are still, however, hotly debated issues. Here we review the recent literature with an emphasis on models that recapitulate observations from human disease.

Heritable Individual-Specific and Allele-Specific Chromatin Signatures in Humans

Abstract: The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific; a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, which suggests that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans.

Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes

Abstract: The use of genome wide single nucleotide polymorphism (SNP) arrays for high resolution molecular cytogenetic analysis using a combination of quantitative and genotype analysis is well established. This study demonstrates that by Mendelian analysis of the SNP genotypes of the parents and a sibling or other appropriate family member to establish phase, it is possible to identify informative loci for each of the four parental haplotypes across each chromosome and map the inheritance of these haplotypes and the position of any crossovers in the proband. The resulting 'karyomap', unlike a karyotype, identifies the parental and grandparental origin of each chromosome and chromosome segment and is unique for every individual being defined by the independent segregation of parental chromosomes and the pattern of non-recombinant and recombinant chromosomes. Karyomapping, therefore, enables both genome wide linkage based analysis of inheritance and detection of chromosome imbalance where either both haplotypes from one parent are present (trisomy) or neither are present (monosomy/deletion). The study also demonstrates that karyomapping is possible at the single cell level following whole genome amplification and, without any prior patient or disease specific test development, provides a universal linkage based methodology for preimplantation genetic diagnosis readily available worldwide.

Function of sperm chromatin structural elements in fertilization and development

Abstract: Understanding how DNA is packaged in the mammalian sperm cell has important implications for human infertility as well as for the cell biology. Recent advances in the study of mammalian sperm chromatin structure and function have altered our perception of this highly condensed, inert chromatin. Sperm DNA is packaged very tightly to protect the DNA during the transit that occurs before fertilization. However, this condensation cannot sacrifice chromosomal elements that are essential for the embryo to access the correct sequences of the paternal genome for proper initiation of the embryonic developmental program. The primary levels of the sperm chromatin structure can be divided into three main categories: the large majority of DNA is packaged by protamines, a smaller amount (2-15%) retains histone-bound chromatin and the DNA is attached to the nuclear matrix at roughly 50 kb intervals. Current data suggest that the latter two structural elements are transferred to the paternal pronucleus after fertilization where they have important functional roles. The nuclear matrix organization is essential for DNA replication, and the histone-bound chromatin identifies genes that are important for embryonic development. These data support the emerging view of the sperm genome as providing, in addition to the paternal DNA sequence, a structural framework that includes molecular regulatory factors that are required for proper embryonic development.

The B chromosomes of the African cichlid fish Haplochromis obliquidens harbour 18S rRNA gene copies.

Abstract: Diverse plant and animal species have B chromosomes, also known as accessory, extra or supernumerary chromosomes. Despite being widely distributed among different taxa, the genomic nature and genetic behavior of B chromosomes are still poorly understood. In this study we describe the occurrence of B chromosomes in the African cichlid fish Haplochromis obliquidens. One or two large B chromosome(s) occurring in 39.6% of the analyzed individuals (both male and female) were identified. To better characterize the karyotype and assess the nature of the B chromosomes, fluorescence in situ hybridization (FISH) was performed using probes for telomeric DNA repeats, 18S and 5S rRNA genes, SATA centromeric satellites, and bacterial artificial chromosomes (BACs) enriched in repeated DNA sequences. The B chromosomes are enriched in repeated DNAs, especially non-active 18S rRNA gene-like sequences. Our results suggest that the B chromosome could have originated from rDNA bearing subtelo/acrocentric A chromosomes through formation of an isochromosome, or by accumulation of repeated DNAs and rRNA gene-like sequences in a small proto-B chromosome derived from the A complement.

High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli.

Abstract: The nuclear space is mostly occupied by chromosome territories and nuclear bodies. Although this organization of chromosomes affects gene function, relatively little is known about the role of nuclear bodies in the organization of chromosomal regions. The nucleolus is the best-studied subnuclear structure and forms around the rRNA repeat gene clusters on the acrocentric chromosomes. In addition to rDNA, other chromatin sequences also surround the nucleolar surface and may even loop into the nucleolus. These additional nucleolar-associated domains (NADs) have not been well characterized. We present here a whole-genome, high-resolution analysis of chromatin endogenously associated with nucleoli. We have used a combination of three complementary approaches, namely fluorescence comparative genome hybridization, high-throughput deep DNA sequencing and photoactivation combined with time-lapse fluorescence microscopy. The data show that specific sequences from most human chromosomes, in addition to the rDNA repeat units, associate with nucleoli in a reproducible and heritable manner. NADs have in common a high density of AT-rich sequence elements, low gene density and a statistically significant enrichment in transcriptionally repressed genes. Unexpectedly, both the direct DNA sequencing and fluorescence photoactivation data show that certain chromatin loci can specifically associate with either the nucleolus, or the nuclear envelope.

Analysis of the Size Distributions of Fetal and Maternal Cell-Free DNA by Paired-End Sequencing

Abstract: BACKGROUND: Noninvasive prenatal diagnosis with cell-free DNA in maternal plasma is challenging because only a small portion of the DNA sample is derived from the fetus. A few previous studies provided size-range estimates of maternal and fetal DNA, but direct measurement of the size distributions is difficult because of the small quantity of cell-free DNA. METHODS: We used high-throughput paired-end sequencing to directly measure the size distributions of maternal and fetal DNA in cell-free maternal plasma collected from 3 typical diploid and 4 aneuploid male pregnancies. As a control, restriction fragments of DNA were also sequenced. RESULTS: Cell-free DNA had a dominant peak at approximately162bpandaminorpeakatapproximately 340 bp. Chromosome Y sequences were rarely longer than 250 bp but were present in sizes of 150 bp at a larger proportion compared with the rest of the sequences. Selective analysis of the shortest fragments generally increased the fetal DNA fraction but did not necessarilyincreasethesensitivityofaneuploidydetection, owing to the reduction in the number of DNA molecules being counted. Restriction fragments of DNA with sizes between 60 bp and 120 bp were preferentially sequenced, indicating that the shotgun sequencing work flow introduced a bias toward shorter fragments. CONCLUSIONS: Our results confirm that fetal DNA is shorter than maternal DNA. The enrichment of fetal DNA by size selection, however, may not provide a dramatic increase in sensitivity for assays that rely on length measurement in situ because of a trade-off between the fetal DNA fraction and the number of molecules being counted. © 2010 American Association for Clinical Chemistry

Loss of pRB causes centromere dysfunction and chromosomal instability

Abstract: Chromosome instability (CIN) is a common feature of tumor cells. By monitoring chromosome segregation, we show that depletion of the retinoblastoma protein (pRB) causes rates of missegregation comparable with those seen in CIN tumor cells. The retinoblastoma tumor suppressor is frequently inactivated in human cancers and is best known for its regulation of the G1/S-phase transition. Recent studies have shown that pRB inactivation also slows mitotic progression and promotes aneuploidy, but reasons for these phenotypes are not well understood. Here we describe the underlying mitotic defects of pRB-deficient cells that cause chromosome missegregation. Analysis of mitotic cells reveals that pRB depletion compromises centromeric localization of CAP-D3/condensin II and chromosome cohesion, leading to an increase in intercentromeric distance and deformation of centromeric structure. These defects promote merotelic attachment, resulting in failure of chromosome congression and an increased propensity for lagging chromosomes following mitotic delay. While complete loss of centromere function or chromosome cohesion would have catastrophic consequences, these more moderate defects allow pRB-deficient cells to proliferate but undermine the fidelity of mitosis, leading to whole-chromosome gains and losses. These observations explain an important consequence of RB1 inactivation, and suggest that subtle defects in centromere function are a frequent source of merotely and CIN in cancer.

Higher-order Genome Organization in Human Disease

Abstract: Genomes are organized into complex higher-order structures by folding of the DNA into chromatin fibers, chromosome domains, and ultimately chromosomes. The higher-order organization of genomes is functionally important for gene regulation and control of gene expression programs. Defects in how chromatin is globally organized are relevant for physiological and pathological processes. Mutations and transcriptional misregulation of several global genome organizers are linked to human diseases and global alterations in chromatin structure are emerging as key players in maintenance of genome stability, aging, and the formation of cancer translocations.

Caenorhabditis elegans chromosome arms are anchored to the nuclear membrane via discontinuous association with LEM-2

Abstract: Although Caenorhabditis elegans was the first multicellular organism with a completely sequenced genome, how this genome is arranged within the nucleus is not known. We determined the genomic regions associated with the nuclear transmembrane protein LEM-2 in mixed-stage C. elegans embryos via chromatin immunoprecipitation. Large regions of several megabases on the arms of each autosome were associated with LEM-2. The center of each autosome was mostly free of such interactions, suggesting that they are largely looped out from the nuclear membrane. Only the left end of the X chromosome was associated with the nuclear membrane. At a finer scale, the large membrane-associated domains consisted of smaller subdomains of LEM-2 associations. These subdomains were characterized by high repeat density, low gene density, high levels of H3K27 trimethylation, and silent genes. The subdomains were punctuated by gaps harboring highly active genes. A chromosome arm translocated to a chromosome center retained its association with LEM-2, although there was a slight decrease in association near the fusion point. Local DNA or chromatin properties are the main determinant of interaction with the nuclear membrane, with position along the chromosome making a minor contribution. Genes in small gaps between LEM-2 associated regions tend to be highly expressed, suggesting that these small gaps are especially amenable to highly efficient transcription. Although our data are derived from an amalgamation of cell types in mixed-stage embryos, the results suggest a model for the spatial arrangement of C. elegans chromosomes within the nucleus.

Uniparental disomy and human disease: an overview.

Abstract: Uniparental disomy (UPD) refers to the situation in which both homologues of a chromosomal region/segment have originated from only one parent. This can involve the entire chromosome or only a small segment. As a consequence of UPD, or uniparental duplication/deficiency of part of a chromosome, there are two types of developmental risk: aberrant dosage of genes regulated by genomic imprinting and homozygosity of a recessive mutation. UPD models generated by reciprocal and Robertsonian translocation heterozygote intercrosses have been a powerful tool to investigate genomic imprinting in mice, whereas novel UPD patients such as those with cystic fibrosis and Prader-Willi syndrome, triggered the clarification of recessive diseases and genomic imprinting disorders in human. Newly developed genomic technologies as well as conventional microsatellite marker methods have been contributing to the functional and mechanistic investigation of UPD, leading to not only the acquisition of clinically valuable information, but also the further clarification of diverse genetic processes and disease pathogenesis.

Chickens possess centromeres with both extended tandem repeats and short non-tandem-repetitive sequences

Abstract: The centromere is essential for faithful chromosome segregation by providing the site for kinetochore assembly. Although the role of the centromere is conserved throughout evolution, the DNA sequences associated with centromere regions are highly divergent among species and it remains to be determined how centromere DNA directs kinetochore formation. Despite the active use of chicken DT40 cells in studies of chromosome segregation, the sequence of the chicken centromere was unclear. Here, we performed a comprehensive analysis of chicken centromere DNA which revealed unique features of chicken centromeres compared with previously studied vertebrates. Centromere DNA sequences from the chicken macrochromosomes, with the exception of chromosome 5, contain chromosome-specific homogenous tandem repetitive arrays that span several hundred kilobases. In contrast, the centromeres of chromosomes 5, 27, and Z do not contain tandem repetitive sequences and span non-tandem-repetitive sequences of only approximately 30 kb. To test the function of these centromere sequences, we conditionally removed the centromere from the Z chromosome using genetic engineering and have shown that that the non-tandem-repeat sequence of chromosome Z is a functional centromere.

Age-dependent chromosomal distribution of male-biased genes in Drosophila

Abstract: We investigated the correlation between the chromosomal location and age distribution of new male-biased genes formed by duplications via DNA intermediates (DNA-level) or by de novo origination in Drosophila. Our genome-wide analysis revealed an excess of young X-linked male-biased genes. The proportion of X-linked male-biased genes then diminishes through time, leading to an autosomal excess of male-biased genes. The switch between X-linked and autosomal enrichment of male-biased genes was also present in the distribution of both protein-coding genes on the D. pseudoobscura neo-X chromosome and microRNA genes of D. melanogaster. These observations revealed that the evolution of male-biased genes is more complicated than the previously detected one-step X→A gene traffic and the enrichment of the male-biased genes on autosomes. The pattern we detected suggests that the interaction of various evolutionary forces such as the meiotic sex chromosome inactivation (MSCI), faster-X effect, and sexual antagonism in the male germline might have shaped the chromosomal distribution of male-biased genes on different evolutionary time scales.

Novel genetic aspects of Klinefelter's syndrome

Abstract: Klinefelter's syndrome (KS) is the most common chromosome aneuploidy in males, characterized by at least one supernu- merary X chromosome. Although extensively studied, the pathophysiology, i.e. the link between the extra X and the phenotype, largely remains unexplained. The scope of this review is to summarize the progress made in recent years on the role of the supernumerary X chromosome with respect to its putative influence on the phenotype. In principal, the parental origin of the X chromosome, gene- dosage effects in conjunction with (possibly skewed) X chromosome inactivation, and—especially concerning spermatogenesis—meiotic failure may play pivotal roles. One of the X chromosomes is inactivated to achieve dosage-compensation in females and probably likewise in KS. Genes from the pseudoautosomal regions and an additional 15% of other genes, however, escape X inactivation and are candidates for putatively constituting the KS phenotype. Examples are the SHOX genes, identified as likely causing the tall stature regularly seen in KS. Lessons learned from comparisons with normal males and especially females as well as other sex chromosomal aneuploidies are presented. In addition, genetic topics concerning fertility and counseling are discussed.

Development of Chromosome-Specific BAC Resources for Genomics of Bread Wheat

Abstract: The large bread wheat genome (1C ∼ 17 Gbp) contains a preponderance of repetitive DNA and the species is polyploid. These characteristics together serve to hamper the molecular analysis of the wheat g

Chromosome spreading of associated transposable elements and ribosomal DNA in the fish Erythrinus erythrinus. Implications for genome change and karyoevolution in fish

Abstract: The fish, Erythrinus erythrinus, shows an interpopulation diversity, with four karyomorphs differing by chromosomal number, chromosomal morphology and heteromorphic sex chromosomes. Karyomorph A has a diploid number of 2n = 54 and does not have differentiated sex chromosomes. Karyomorph D has 2n = 52 chromosomes in females and 2n = 51 in males, and it is most likely derived from karyomorph A by the differentiation of a multiple X1X2Y sex chromosome system. In this study, we analyzed karyomorphs A and D by means of cytogenetic approaches to evaluate their evolutionary relationship. Conspicuous differences in the distribution of the 5S rDNA and Rex3 non-LTR retrotransposon were found between the two karyomorphs, while no changes in the heterochromatin and 18S rDNA patterns were found between them. Rex3 was interstitially dispersed in most chromosomes. It had a compartmentalized distribution in the centromeric regions of only two acrocentric chromosomes in karyomorph A. In comparison, in karyomorph D, Rex3 was found in 22 acrocentric chromosomes in females and 21 in males. All 5S rDNA sites co-localized with Rex3, suggesting that these are associated in the genome. In addition, the origin of the large metacentric Y chromosome in karyomorph D by centric fusion was highlighted by the presence of internal telomeric sites and 5S rDNA/Rex3 sites on this chromosome. We demonstrated that some repetitive DNAs (5S rDNA, Rex3 retroelement and (TTAGGG)n telomeric repeats) were crucial for the evolutionary divergence inside E. erythrinus. These elements were strongly associated with the karyomorphic evolution of this species. Our results indicate that chromosomal rearrangements and genomic modifications were significant events during the course of evolution of this fish. We detected centric fusions that were associated with the differentiation of the multiple sex chromosomes in karyomorph D, as well as a surprising increase of associated 5S rDNA/Rex3 loci, in contrast to karyomorph A. In this sense, E. erythrinus emerges as an excellent model system for better understanding the evolutionary mechanisms underlying the huge genome diversity in fish. This organism can also contribute to understanding vertebrate genome evolution as a whole.

Genetic conflict and sex chromosome evolution.

Abstract: Chromosomal sex determination systems create the opportunity for the evolution of selfish genetic elements that increase the transmission of one sex chromosome at the expense of its homolog. Because such selfish elements on sex chromosomes can reduce fertility and distort the sex ratio of progeny, unlinked suppressors are expected to evolve, bringing different regions of the genome into conflict over the meiotic transmission of the sex chromosomes. Here we argue that recurrent genetic conflict over sex chromosome transmission is an important evolutionary force that has shaped a wide range of seemingly disparate phenomena including the epigenetic regulation of genes expressed in the germline, the distribution of genes in the genome, and the evolution of hybrid sterility between species.

Human interphase chromosomes: a review of available molecular cytogenetic technologies.

Abstract: Human karyotype is usually studied by classical cytogenetic (banding) techniques. To perform it, one has to obtain metaphase chromosomes of mitotic cells. This leads to the impossibility of analyzing all the cell types, to moderate cell scoring, and to the extrapolation of cytogenetic data retrieved from a couple of tens of mitotic cells to the whole organism, suggesting that all the remaining cells possess these genomes. However, this is far from being the case inasmuch as chromosome abnormalities can occur in any cell along ontogeny. Since somatic cells of eukaryotes are more likely to be in interphase, the solution of the problem concerning studying postmitotic cells and larger cell populations is interphase cytogenetics, which has become more or less applicable for specific biomedical tasks due to achievements in molecular cytogenetics (i.e. developments of fluorescence in situ hybridization -- FISH, and multicolor banding -- MCB). Numerous interphase molecular cytogenetic approaches are restricted to studying specific genomic loci (regions) being, however, useful for identification of chromosome abnormalities (aneuploidy, polyploidy, deletions, inversions, duplications, translocations). Moreover, these techniques are the unique possibility to establish biological role and patterns of nuclear genome organization at suprachromosomal level in a given cell. Here, it is to note that this issue is incompletely worked out due to technical limitations. Nonetheless, a number of state-of-the-art molecular cytogenetic techniques (i.e multicolor interphase FISH or interpahase chromosome-specific MCB) allow visualization of interphase chromosomes in their integrity at molecular resolutions. Thus, regardless numerous difficulties encountered during studying human interphase chromosomes, molecular cytogenetics does provide for high-resolution single-cell analysis of genome organization, structure and behavior at all stages of cell cycle.

A Genomewide Association Study of Nicotine and Alcohol Dependence in Australian and Dutch Populations

Abstract: Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1 M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10,000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10(-8)) for ND (rs964170 in ARHGAP10 on chromosome 4, p = 4.43 x 10(-8)) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10(-9)), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10(-9)) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10(-18))). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepresentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be required before the detailed causes of comorbidity between AD and ND are understood.

Intra- and inter-chromosomal interactions correlate with CTCF binding genome wide

Abstract: A prime goal in systems biology is the comprehensive use of existing high-throughput genomic datasets to gain a better understanding of chromatin organization and genome function. In this report, we use chromatin immunoprecipitation (ChIP) data that map protein-binding sites on the genome, and Hi-C data that map interactions between DNA fragments in the genome in an integrative approach. We first reanalyzed the contact map of the human genome as determined with Hi-C and found that long-range interactions are highly nonrandom; the same DNA fragments are often found interacting together. We then show using ChIP data that these interactions can be explained by the action of the CCCTC-binding factor (CTCF). These CTCF-mediated interactions are found both within chromosomes and in between different chromosomes. This makes CTCF a major organizer of both the structure of the chromosomal fiber within each individual chromosome and of the chromosome territories within the cell nucleus.

Diversity of chromosomal karyotypes in maize and its relatives.

Abstract: Maize is a highly diverse species on the gene sequence level. With the recent development of methods to distinguish each of the 10 pairs of homologues in somatic root tip spreads, a wide collection of maize lines was subjected to karyotype analysis to serve as a reference for the community and to examine the spectrum of chromosomal features in the species. The core nested association mapping progenitor collection and additional selections of diversity lines were examined. Commonly used inbred lines were included in the analysis. The centromere 4 specific repeat and ribosomal RNA loci were invariant. The CentC centromere repeat exhibited extensive differences in quantity on any particular chromosome across lines. Knob heterochromatin was highly variable with locations at many sites in the genome. Lastly, representative examples from other species in the genus Zea (teosintes) were examined, which provide information on the evolution of chromosomal features.

Somatic Genome Variations in Health and Disease

Abstract: It is hard to imagine that all the cells of the human organism (about 1014) share identical genome. Moreover, the number of mitoses (about 1016) required for the organism’s development and maturation during ontogeny suggests that at least a proportion of them could be abnormal leading, thereby, to large-scale genomic alterations in somatic cells. Experimental data do demonstrate such genomic variations to exist and to be involved in human development and interindividual genetic variability in health and disease. However, since current genomic technologies are mainly based on methods, which analyze genomes from a large pool of cells, intercellular or somatic genome variations are significantly less appreciated in modern bioscience. Here, a review of somatic genome variations occurring at all levels of genome organization (i.e. DNA sequence, subchromosomal and chromosomal) in health and disease is presented. Looking through the available literature, it was possible to show that the somatic cell genome is extremely variable. Additionally, being mainly associated with chromosome or genome instability (most commonly manifesting as aneuploidy), somatic genome variations are involved in pathogenesis of numerous human diseases. The latter mainly concerns diseases of the brain (i.e. autism, schizophrenia, Alzheimer’s disease) and immune system (autoimmune diseases), chromosomal and some monogenic syndromes, cancers, infertility and prenatal mortality. Taking into account data on somatic genome variations and chromosome instability, it becomes possible to show that related processes can underlie non-malignant pathology such as (neuro)degeneration or other local tissue dysfunctions. Together, we suggest that detection and characterization of somatic genome behavior and variations can provide new opportunities for human genome research and genetics.