Showing papers on "Chromosome 22 published in 2009"
TL;DR: Ch Chromosome duplication of the region that is deleted in patients with DGS/VCFS has been reported, establishing a new genomic duplication syndrome complementary to the 22q11.2 deletion syndrome, and TBX1 gain-of-function mutations, resulting in the same phenotypic spectrum as haploinsufficiency caused by loss of function mutations or deletions have been observed.
189 citations
TL;DR: The results from the genome-wide single nucleotide polymorphism array analysis suggest that INI1 is the primary tumor suppressor gene involved in the development of rhabdoid tumors with no second locus identified.
Abstract: Purpose: A high-resolution genomic profiling and comprehensive targeted analysis of INI1/SMARCB1 of a large series of pediatric rhabdoid tumors was done. The aim was to identify regions of copy number change and loss of heterozygosity (LOH) that might pinpoint additional loci involved in the development or progression of rhabdoid tumors and define the spectrum of genomic alterations of INI1 in this malignancy. Experimental Design: A multiplatform approach using Illumina single nucleotide polymorphism-based oligonucleotide arrays, multiplex ligation-dependent probe amplification, fluorescence in situ hybridization, and coding sequence analysis was used to characterize genome-wide copy number changes, LOH, and genomic alterations of INI1/SMARCB1 in a series of pediatric rhabdoid tumors. Results: The biallelic alterations of INI1 that led to inactivation were elucidated in 50 of 51 tumors. INI1 inactivation was shown by a variety of mechanisms, including deletions, mutations, and LOH. The results from the array studies highlighted the complexity of rearrangements of chromosome 22 compared with the low frequency of alterations involving the other chromosomes. Conclusions: The results from the genome-wide single nucleotide polymorphism array analysis suggest that INI1 is the primary tumor suppressor gene involved in the development of rhabdoid tumors with no second locus identified. In addition, we did not identify hotspots for the breakpoints in sporadic tumors with deletions of chromosome 22q11.2. By employing a multimodality approach, the wide spectrum of alterations of INI1 can be identified in the majority of patients, which increases the clinical utility of molecular diagnostic testing.
181 citations
TL;DR: Comparison of the Atlantic salmon chromosome map with that of rainbow trout provides strong evidence for conservation of large syntenic blocks in these species, corresponding to entire chromosome arms in the rainbow trout.
Abstract: Most teleost species, especially freshwater groups such as the Esocidae which are the closest relatives of salmonids, have a karyotype comprising 25 pairs of acrocentric chromosomes and 48–52 chromosome arms. After the common ancestor of salmonids underwent a whole genome duplication, its karyotype would have 100 chromosome arms, and this is reflected in the modal range of 96–104 seen in extant salmonids (e.g., rainbow trout). The Atlantic salmon is an exception among the salmonids as it has 72–74 chromosome arms and its karyotype includes 12 pairs of large acrocentric chromosomes, which appear to be the result of tandem fusions. The purpose of this study was to integrate the Atlantic salmon's linkage map and karyotype and to compare the chromosome map with that of rainbow trout. The Atlantic salmon genetic linkage groups were assigned to specific chromosomes in the European subspecies using fluorescence in situ hybridization with BAC probes containing genetic markers mapped to each linkage group. The genetic linkage groups were larger for metacentric chromosomes compared to acrocentric chromosomes of similar size. Comparison of the Atlantic salmon chromosome map with that of rainbow trout provides strong evidence for conservation of large syntenic blocks in these species, corresponding to entire chromosome arms in the rainbow trout. It had been suggested that some of the large acrocentric chromosomes in Atlantic salmon are the result of tandem fusions, and that the small blocks of repetitive DNA in the middle of the arms represent the sites of chromosome fusions. The finding that the chromosomal regions on either side of the blocks of repetitive DNA within the larger acrocentric chromosomes correspond to different rainbow trout chromosome arms provides support for this hypothesis.
127 citations
TL;DR: The study of over 700 species, from algae to humans, reveals that specific DNA sequences, have an optimal territory within the centromere-telomere field, and predictions can be made concerning gene organization, gene function and chromosome evolution.
Abstract: The study of over 700 species, from algae to humans, reveals that specific DNA sequences, have an optimal territory within the centromere-telomere field. These DNA sequences have maintained their territory within the chromosome field for millions of years irrespective of variation in arm length, of change in chromosome type and of species evolution. Some of these DNA sequences have been isolated biochemically or analysed at the molecular level. They include, e.g., the proximal heterochromatic segments, the genes for ribosomal RNA, and the telomeric heterochromatin. Order prevails in the eukaryotic chromosome.
This order allows classification of genes, rearrangements and chromosomes on a genetic basis. Genes are classified as centrons, medons and telons. Rearrangements are classified as: conservative, discordant, disruptive, destructive and incompatible. Chromosomes are also classified depending on their length, arm size and number. These chromosome properties and features now acquire an organizatory meaning which they lacked previously.
The available molecular information supports the evidence from the field. The study of the split gene reveals that it is the relative position of the DNA sequences which determines their function.
On the basis of the chromosome field, predictions can be made concerning gene organization, gene function and chromosome evolution.
80 citations
TL;DR: A microarray-based comparative genomic hybridization analysis of 60 spontaneous canine intracranial tumors was performed to examine the degree to which dog and human patients exhibit aberrations of ancestrally related chromosome regions, consistent with a shared pathogenesis.
Abstract: Numerous attributes render the domestic dog a highly pertinent model for cancer-associated gene discovery. We performed microarray-based comparative genomic hybridization analysis of 60 spontaneous canine intracranial tumors to examine the degree to which dog and human patients exhibit aberrations of ancestrally related chromosome regions, consistent with a shared pathogenesis. Canine gliomas and meningiomas both demonstrated chromosome copy number aberrations (CNAs) that share evolutionarily conserved synteny with those previously reported in their human counterpart. Interestingly, however, genomic imbalances orthologous to some of the hallmark aberrations of human intracranial tumors, including chromosome 22/NF2 deletions in meningiomas and chromosome 1p/19q deletions in oligodendrogliomas, were not major events in the dog. Furthermore, and perhaps most significantly, we identified highly recurrent CNAs in canine intracranial tumors for which the human orthologue has been reported previously at low frequency but which have not, thus far, been associated intimately with the pathogenesis of the tumor. The presence of orthologous CNAs in canine and human intracranial cancers is strongly suggestive of their biological significance in tumor development and/or progression. Moreover, the limited genetic heterogenity within purebred dog populations, coupled with the contrasting organization of the dog and human karyotypes, offers tremendous opportunities for refining evolutionarily conserved regions of tumor-associated genomic imbalance that may harbor novel candidate genes involved in their pathogenesis. A comparative approach to the study of canine and human intracranial tumors may therefore provide new insights into their genetic etiology, towards development of more sophisticated molecular subclassification and tailored therapies in both species.
76 citations
TL;DR: The data suggest that vision and hearing impairment, seizures, failure to thrive and recurrent infections, particularly otitis media, are common in this syndrome.
Abstract: Emanuel syndrome is characterized by multiple congenital anomalies and developmental disability. It is caused by the presence of a supernumerary derivative chromosome that contains material from chromosomes 11 and 22. The origin of this imbalance is 3:1 malsegregation of a parental balanced translocation between chromosomes 11 and 22, which is the most common recurrent reciprocal translocation in humans. Little has been published on the clinical features of this syndrome since the 1980s and information on natural history is limited. We designed a questionnaire to collect information from families recruited through an international online support group, Chromosome 22 Central. Data gathered include information on congenital anomalies, medical and surgical history, developmental and behavioral issues, and current abilities. We received information on 63 individuals with Emanuel syndrome, ranging in age from newborn to adulthood. As previously recognized, congenital anomalies were common, the most frequent being ear pits (76%), micrognathia (60%), heart malformations (57%), and cleft palate (54%). Our data suggest that vision and hearing impairment, seizures, failure to thrive and recurrent infections, particularly otitis media, are common in this syndrome. Psychomotor development is uniformly delayed, however the majority of individuals (over 70%) eventually learn to walk with support. Language development and ability for self-care are also very impaired. This study provides new information on the clinical spectrum and natural history of Emanuel syndrome for families and physicians caring for these individuals.
71 citations
TL;DR: 17 new cases of inverted duplication with terminal deletion are described, demonstrating that U-type exchange is the most frequent mechanism for this rearrangement and can be observed on most, or perhaps all, chromosome arms.
Abstract: Background: Chromosomal rearrangements resulting in an interstitial inverted duplication with concomitant terminal deletion were first described for the short arm of chromosome 8 in 1976. Since then, this type of alteration has been identified and characterised for most chromosome arms. Three mechanisms are commonly proposed to explain the origin of this type of rearrangement. All three mechanisms involve formation of a dicentric chromosome that then breaks in a subsequent meiotic division to produce a monocentric duplicated and deleted chromosome. However, the events leading to the formation of the dicentric chromosome differ between the mechanisms. In one mechanism, either parent carries a paracentric inversion. This results in formation of a loop during meiotic pairing with a recombination event occurring in the loop. In the second mechanism, inverted low copy repeats in the same chromosome arm allow partial folding of one homologue onto itself with a recombination event between the inverted repeats. The third mechanism involves a pre-meiotic double-strand break with subsequent fusion, or U-type exchange, between the sister chromatids. The first two mechanisms require a single copy region to exist between the duplicated and deleted regions on the derivative chromosome, and therefore high resolution analysis of the rearrangement can be used to distinguish between these mechanisms. Methods and results: Using G-banded chromosome analysis, fluorescence in situ hybridisation (FISH) and array comparative genomic hybridisation (CGH), we describe 17 new cases of inverted duplication with terminal deletion of 2q, 4p, 5p, 6q, 8p, 9p, 10q, 13q, 15q, 18p, 18q, and 22q. Conclusions: These new cases, combined with previously described cases, demonstrate that U-type exchange is the most frequent mechanism for this rearrangement and can be observed on most, or perhaps all, chromosome arms.
71 citations
TL;DR: Chromosome location of H3-H4 histone gene clusters seem to be highly conservative in Acrididae grasshoppers, which is most parsimoniously explained by common ancestry.
Abstract: We analyse chromosome location of H3 and H4 histone gene clusters by fluorescence in-situ hybridization (FISH) in 35 species of Acrididae grasshoppers belonging to seven subfamilies. As in other organisms, H3 and H4 co-localized in the same chromosome region in the 11 species where double FISH was performed with the H3 and H4 DNA probes. Chromosome location of H3-H4 histone gene clusters showed high regularity in the species analysed, with all of them carrying a single H3-H4 cluster in an autosome which, in most cases, was located interstitially in the proximal chromosome third. In 17 out of the 21 species with 2n♂ = 23 acrocentric chromosomes, the H3-H4-carrying autosome was about eighth in order of decreasing size. Two of the four exceptions changed H3-H4 localization to proximal (Pezotettix giornae) or distal (Tropidopola graeca) in the eighth-sized autosome, but the remainder (the two Eyprepocnemis species) showed the H3-H4 cluster distally located in the second-sized autosome. All 14 species with 2n♂ = 17 chromosomes (including three long metacentric autosome pairs, five acrocentric autosome pairs and an acrocentric X chromosome) carried an interstitial H3-H4 cluster in the short arm of the smallest of the three long metacentric pairs. These results suggest that chromosome location of H3-H4 histone gene clusters seem to be highly conservative in Acrididae grasshoppers. The change in H3-H4 location from the acrocentric medium-sized autosome in the 2n♂ = 23 karyotype to the long metacentric autosome in the 2n♂ = 17 karyotype is most parsimoniously explained by common ancestry, i.e. by the involvement of the H3-H4-carrying acrocentric in the centric fusion that gave rise to the smallest of the three long metacentric autosomes of 2n♂ = 17 species.
69 citations
65 citations
TL;DR: Differences in nucleotide diversity and the proportion of variant sites are significantly lower for nonsynonymous sites than for synonymous sites, introns, or pseudogenes, implying that natural selection has operated effectively in preserving the amino acid sequences of the Y chromosome's X-degenerate proteins during the last approximately 100,000 years of human history.
Abstract: Y-linked single-nucleotide polymorphisms (SNPs) have served as powerful tools for reconstructing the worldwide genealogy of human Y chromosomes and for illuminating patrilineal relationships among modern human populations. However, there has been no systematic, worldwide survey of sequence variation within the protein-coding genes of the Y chromosome. Here we report and analyze coding sequence variation among the 16 single-copy "X-degenerate" genes of the Y chromosome. We examined variation in these genes in 105 men representing worldwide diversity, resequencing in each man an average of 27 kb of coding DNA, 40 kb of intronic DNA, and, for comparison, 15 kb of DNA in single-copy Y-chromosomal pseudogenes. There is remarkably little variation in X-degenerate protein sequences: two chromosomes drawn at random differ on average by a single amino acid, with half of these differences arising from a single, conservative Asp-->Glu mutation that occurred approximately 50,000 years ago. Further analysis showed that nucleotide diversity and the proportion of variant sites are significantly lower for nonsynonymous sites than for synonymous sites, introns, or pseudogenes. These differences imply that natural selection has operated effectively in preserving the amino acid sequences of the Y chromosome's X-degenerate proteins during the last approximately 100,000 years of human history. Thus our findings are at odds with prominent accounts of the human Y chromosome's imminent demise.
57 citations
TL;DR: One patient with Ph1 negative CML had no detectable additional chromosomal material on any chromosome including chromosome 9, which gives further support to the view that there is indeed a translocation in Ph1 positive patients.
Abstract: . Chromosome 9 had additional chromosomal material at the end of the long arm in 15 of 16 patients with Ph1 positive CML. The remaining patient had a normal chromosome 9but additional material on 19. The amount of additional material was approximately the same as that lacking on chromosome 22. Translocations between 9 and 22, and 19 and 22, respectively, are therefore suggested. One patient with Ph1 negative CML had no detectable additional chromosomal material on any chromosome including chromosome 9, which gives further support to the view that there is indeed a translocation in Ph1 positive patients. Extra chromosomes appeared in two of three Ph1 positive patients in the blastic stage. Both patients had extra number 8 chromosomes and double Ph1, and one patient had further extra chromosomes, i.e. 7, 11, 12, 16, 17 and 19.
TL;DR: Genetic compensation, which is consistent with the normal phenotype of the father, was shown through quantitative-expression analyses of genes located within the genetic region associated with the DiGeorge syndrome, a case of genetic compensation in a human genomic disorder.
Abstract: Cytogenetic studies of the parents of a girl with the DiGeorge (or velocardiofacial) syndrome, who carried a deletion at 22q11.2, revealed an unexpected rearrangement of both 22q11.2 regions in the unaffected father. He carried a 22q11.2 deletion on one copy of chromosome 22 and a reciprocal 22q11.2 duplication on the other copy of chromosome 22. Genetic compensation, which is consistent with the normal phenotype of the father, was shown through quantitative-expression analyses of genes located within the genetic region associated with the DiGeorge syndrome. This finding has implications for genetic counseling and represents a case of genetic compensation in a human genomic disorder.
TL;DR: The introduction of effective TKIs in the treatment of Ph+ ALL has introduced several avenues of research in a disease that was hitherto difficult to treat.
Abstract: The Philadelphia (Ph) chromosome, a short chromosome 22, is the most frequent cytogenetic abnormality in adult patients with acute lymphoblastic leukemia (ALL). It occurs in approximately 20% to 30% of adults and in about 5% of children with this disease. The incidence rises with age and occurs in approximately 50% of patients older than 50 years. This article reviews the treatment regimens for Ph+ ALL, including imatinib and second generation tyrosine kinase inhibitors (TKIs). The introduction of effective TKIs in the treatment of Ph+ ALL has introduced several avenues of research in a disease that was hitherto difficult to treat.
TL;DR: The FISH results helped to solve two discrepancies in the potato genetic map related to chromosomes 8 and 12, and the significance of the potato cytogenetic map for extended FISH studies in potato and related Solanaceae is discussed.
Abstract: A cytogenetic map has been developed for diploid potato (Solanum tuberosum), in which the arms of the 12 potato bivalents can be identified in pachytene complements using multicolor fluorescence in situ hybridization (FISH) with a set of 60 genetically anchored bacterial artificial chromosome (BAC) clones from the RHPOTKEY BAC library. This diagnostic set of selected BACs (five per chromosome) hybridizes to euchromatic regions and corresponds to well-defined loci in the ultradense genetic map, and with these probes a new detailed and reliable pachytene karyotype could be established. Chromosome size has been estimated both from microscopic length measurements and from 4′,6-diamidino-2-phenylindole fluorescence-based DNA content measurements. In both approaches, chromosome 1 is the largest (100–115 Mb) and chromosome 11 the smallest (49–53 Mb). Detailed measurements of mega-base-pair to micrometer ratios have been obtained for chromosome 5, with average values of 1.07 Mb/μm for euchromatin and 3.67 Mb/μm for heterochromatin. In addition, our FISH results helped to solve two discrepancies in the potato genetic map related to chromosomes 8 and 12. Finally, we discuss the significance of the potato cytogenetic map for extended FISH studies in potato and related Solanaceae, which will be especially beneficial for the potato genome-sequencing project.
TL;DR: For all analyzed B-chromosome-derived transcripts, similar A chromosome-encoded sequences were found which supports an A-derived origin of rye B chromosomes and provides evidence that B chromosome influences in trans the transcription of A chromosome sequences.
Abstract: B chromosomes (Bs) are dispensable components of the genomes of numerous species. To test whether the transcriptome of a host is influenced by Bs, we looked for differences in expression in response to additional Bs. Comparative complementary DNA amplified fragment length polymorphism experiments resulted in the identification of 16 putative B-chromosome-associated transcripts. This comprises 0.7% of the total transcript number and indicates a low activity of Bs. We also provide evidence that B chromosome influences in trans the transcription of A chromosome sequences. The B-specific transcribed sequences B1334, B8149, and B2465 belong to high-copy families with similarity to mobile elements. For all analyzed B-chromosome-derived transcripts, similar A chromosome-encoded sequences were found which supports an A-derived origin of rye B chromosomes.
TL;DR: Degenerate primers based on human and mouse obesity gene sequencing data were used in the reverse transcriptase-polymerase chain reaction (RT-PCR) of total RNA from pig white adipose tissue, and the border of conserved synteny is concluded to be in the 7q31-7q32 region of the human chromosome.
Abstract: Summary
Degenerate primers based on human and mouse obesity gene (OBS) sequencing data were used in the reverse transcriptase-polymerase chain reaction (RT-PCR) of total RNA from pig white adipose tissue. Both strands of the resultant pig- specific 325 bp DNA fragment were sequenced. Comparison of the obtained sequence with known sequences revealed an 86% identity with the human and 84% identity with the mouse OBS cDNA. The OBS gene was physically mapped to pig chromosome 18 by PCR analysis of somatic cell hybrids, using pig-specific primers. This result is consistent with the recent assignment of the human OBS gene to chromosome 7 and the observation made by comparative mapping that by using a human chromosome 7 specific library two segments of conserved synteny were detected on porcine chromosomes 9 and 18. We conclude the border of conserved synteny to be in the 7q31-7q32 region of the human chromosome.
TL;DR: The results indicate that all those closely related species have experienced a recent extensive process of autosomal rearrangement in which, except for ASP, there is still complete conservation of sex chromosomes homologies.
Abstract: Traditionally comparative cytogenetic studies are based mainly on banding patterns. Nevertheless, when dealing with species with highly rearranged genomes, as in Akodon species, or with other highly divergent species, cytogenetic comparisons of banding patterns prove inadequate. Hence, comparative chromosome painting has become the method of choice for genome comparisons at the cytogenetic level since it allows complete chromosome probes of a species to be hybridized in situ onto chromosomes of other species, detecting homologous genomic regions between them. In the present study, we have explored the highly rearranged complements of the Akodon species using reciprocal chromosome painting through species-specific chromosome probes obtained by chromosome sorting. The results revealed complete homology among the complements of Akodon sp. n. (ASP), 2n = 10; Akodon cursor (ACU), 2n = 15; Akodon montensis (AMO), 2n = 24; and Akodon paranaensis (APA), 2n = 44, and extensive chromosome rearrangements have been detected within the species with high precision. Robertsonian and tandem rearrangements, pericentric inversions and/or centromere repositioning, paracentric inversion, translocations, insertions, and breakpoints, where chromosomal rearrangements, seen to be favorable, were observed. Chromosome painting using the APA set of 21 autosomes plus X and Y revealed eight syntenic segments that are shared with A. montensis, A. cursor, and ASP, and one syntenic segment shared by A. montensis and A. cursor plus five exclusive chromosome associations for A. cursor and six for ASP chromosome X, except for the heterochromatin region of ASP X, and even chromosome Y shared complete homology among the species. These data indicate that all those closely related species have experienced a recent extensive process of autosomal rearrangement in which, except for ASP, there is still complete conservation of sex chromosomes homologies.
TL;DR: The fourth chromosome of Drosophila melanogaster has a number of unique properties that make it a convenient model for the study of chromatin structure as mentioned in this paper, and both cytological and biochemical studies have demonstrated that chromosome 4 is associated with heterochromatic marks, such as HOG protein 1 and histone 3 lysine 9 methylation Chromosome 4 is also marked by POF (painting-of-fourth), a chromosome 4-specific chromosomal protein, and utilizes a dedicated histone methyltransferase, EGG Studies of chromosome 4 have helped
Abstract: The fourth chromosome of Drosophila melanogaster has a number of unique properties that make it a convenient model for the study of chromatin structure Only 42 Mb overall, the 12 Mb distal arm of chromosome 4 seen in polytene chromosomes combines characteristics of heterochromatin and euchromatin This domain has a repeat density of ~35%, comparable to some pericentric chromosome regions, while maintaining a gene density similar to that of the other euchromatic chromosome arms Studies of position-effect variegation have revealed that heterochromatic and euchromatic domains are interspersed on chromosome 4, and both cytological and biochemical studies have demonstrated that chromosome 4 is associated with heterochromatic marks, such as heterochromatin protein 1 and histone 3 lysine 9 methylation Chromosome 4 is also marked by POF (painting-of-fourth), a chromosome 4-specific chromosomal protein, and utilizes a dedicated histone methyltransferase, EGG Studies of chromosome 4 have helped to shape our u
TL;DR: An infant diagnosed with Goldenhar syndrome (GS) phenotype is reported who developed an atypical teratoid rhabdoid tumor of the brain due to a distal deletion of the chromosome 22q11.2 region encompassing the INI1/SMARCB1 tumor suppressor.
Abstract: Chromosome-specific low copy repeats (LCRs) are implicated in several clinically significant microdeletion and microduplication syndromes. The well-recognized phenotype of DiGeorge/velocardiofacial syndrome (DG/VCF) results from deletions of the long arm of chromosome 22 (22q11.2) mediated by the proximal LCRs in this region. More recent evidence suggests that the distal LCRs within 22q11.2 are also implicated in microdeletions and microduplications with less characterized phenotypes. Here we report on an infant diagnosed with Goldenhar syndrome (GS) phenotype who developed an atypical teratoid rhabdoid tumor (AT/RT) of the brain due to a distal deletion of the chromosome 22q11.2 region encompassing the INI1/SMARCB1 tumor suppressor. We also discuss the phenotype of patients with germline deletions of this region and the possible implication of the 22q11.2 region in the GS.
TL;DR: In an isolated population of root voles chromosomal polymorphism of the Robertsonian type was discovered and was caused by centric fission of one chromosome pair (m8).
Abstract: The karyotypes of root voles, Microtus oeconomus (Pallas) from different localities in Fennoscandia are described. The basic chromosome number is 2n=30. The autosome pairs may be divided into three types on the basis of centromeric location: 11 m, 2 sm and 1 st chromosome pairs. The sm1 and sm2 are the longest and shortest chromosomes of the karyotype, respectively. The X chromosome, identified by autoradiography, is an m chromosome constituting 6.0 per cent of the total length of the female haploid set. The Y chromosome is an st chromosome and the next shortest chromosome of the karyotype.
In an isolated population of root voles chromosomal polymorphism of the Robertsonian type was discovered. It was caused by centric fission of one chromosome pair (m8). Wild-captured animals with two (2n=31) and four (2n=32) telocentric chromosomes were found.
TL;DR: The evolutionary history of chromosome 6 in primates was investigated in detail and it was found that the primate ancestor had a homologous chromosome with the same marker order, but with the centromere located at 6p22.1.
Abstract: Molecular cytogenetics provides a visual, pictorial record of the tree of life, and in this respect the fusion origin of human chromosome 2 is a well-known paradigmatic example. Here we report on a variant chromosome 6 in which the centromere jumped to 6p22.1. ChIP-chip experiments with antibodies against the centromeric proteins CENP-A and CENPC exactly defined the neocentromere as lying at chr6:26,407–26,491 kb. We investigated in detail the evolutionary history of chromosome 6 in primates and found that the primate ancestor had a homologous chromosome with the same marker order, but with the centromere located at 6p22.1. Sometime between 17 and 23 million years ago (Mya), in the common ancestor of humans and apes, the centromere of chromosome 6 moved from 6p22.1 to its current location. The neocentromere we discovered, consequently, has jumped back to the ancestral position, where a latent centromereforming potentiality persisted for at least 17 Myr. Because all living organisms form a tree of life, as first conceived by Darwin, evolutionary perspectives can provide compelling underlying explicative grounds for contemporary genomic phenomena.
TL;DR: 35 sequence-tagged site (STS) primers were designed based on EST sequences distributed on homology group 1 chromosomes of Triticum aestivum and used to screen specific markers for chromosome 1RS of Secale cereale and were proved to be specific to chromosomes 1RS.
Abstract: Molecular markers are important tools that have been used to identify the short arm of rye chromosome 1R (1RS) which contains many useful genes introgressed into wheat background. Wheat expressed sequence tag (EST) sequences are valuable for developing molecular markers since ESTs are derived from gene transcripts and more likely to be conserved between wheat and its relative species. In the present study, 35 sequence-tagged site (STS) primers were designed based on EST sequences distributed on homology group 1 chromosomes of Triticum aestivum and used to screen specific markers for chromosome 1RS of Secale cereale . Two primer pairs different from the early studies, STS WE3 , which amplified a 1680-bp and a 1750-bp fragment, and STS WE126 , which produced a 850-bp fragment from rye genome, were proved to be specific to chromosome 1RS since the corresponding fragments were only amplified from 1R chromosome addition line and wheat-rye lines with chromosome 1RS, but not from wheat-rye 2R-7R chromosome addit...
TL;DR: It is concluded that a large subset of human chromosomes has a preferred probabilistic arrangement in WI38 cells and that the resulting chromosomal associations show tissue origin specificity.
Abstract: There is growing evidence that chromosome territories have a probabilistic non-random arrangement within the cell nucleus of mammalian cells. Other than their radial positioning, however, our knowledge of the degree and specificity of chromosome territory associations is predominantly limited to studies of pair-wise associations. In this study we have investigated the association profiles of eight human chromosome pairs (numbers 1, 2, 3, 4, 6, 7, 8, 9) in the cell nuclei of G0-arrested WI38 diploid lung fibroblasts. Associations between heterologous chromosome combinations ranged from 52% to 78% while the homologous chromosome pairs had much lower levels of association (3–25%). A geometric computational method termed the Generalized Median Graph enabled identification of the most probable arrangement of these eight chromosome pairs. Approximately 41% of the predicted associations are present in any given nucleus. The association levels of several chromosome pairs were very similar in a series of lung fibroblast cell lines but strikingly different in skin and colon derived fibroblast cells. We conclude that a large subset of human chromosomes has a preferred probabilistic arrangement in WI38 cells and that the resulting chromosomal associations show tissue origin specificity. J. Cell. Physiol. 221: 120–129, 2009. © 2009 Wiley-Liss, Inc
TL;DR: The results presented here extend the linkage group on pig chromosome 5 and are in accordance with conserved synteny between human chromosome 12, cattle chromosome 5, mouse chromosome 10 and pig chromosome5.
Abstract: Investigation of published sequence data from the porcine insulin-like growth factor 1 (IGF1) gene, resulted in the detection of a microsatellite in the first intron of the gene. Polymerase chain reaction (PCR) primers flanking the (CA)19 repeat were constructed. Polymorphism and Mendelian segregation were documented in a three-generation pedigree and allele frequencies were determined in 74 unrelated animals from four different breeds. Seven alleles were encountered. Linkage analysis was performed in a large pedigree established for gene mapping. Linkage between the IGF1 microsatellite and an anonymous microsatellite marker, S0005, was detected. Furthermore, IGF1 and S0005 was found to be linked to the porcine submaxillary gland mucin (MUC) gene, previously assigned to chromosome 5. The results presented here extend the linkage group on pig chromosome 5 and are in accordance with conserved synteny between human chromosome 12, cattle chromosome 5, mouse chromosome 10 and pig chromosome 5.
TL;DR: Evidence is provided suggesting that nuclear architecture and location of specific genetic loci within chromosome territories may influence their participation in intrachromosomal or interchromosomal rearrangements in human thyroid cells.
Abstract: Chromosomal rearrangements in human cancers are of two types, interchromosomal, which are rearrangements that involve exchange between loci located on different chromosomes, and intrachromosomal, which are rearrangements that involve loci located on the same chromosome. The type of rearrangement that typically activates a specific oncogene may be influenced by its nuclear location and that of its partner. In interphase nuclei, each chromosome occupies a distinct three-dimensional (3D) territory that tends to not overlap the territories of other chromosomes. It is also known that after double strand breaks in the genome, mobility of free DNA ends is limited. These considerations suggest that loci located deep within a chromosomal territory might not participate in interchromosomal rearrangements as readily as in intrachromosomal rearrangements. To test this hypothesis, we used fluorescence in situ hybridization with 3D high-resolution confocal microscopy to analyze the positions of six oncogenes known to be activated by recombination in human cancer cells. We found that loci involved in interchromosomal rearrangements were located closer to the periphery of chromosome territories as compared with the loci that were involved in intrachromosomal inversions. The results of this study provide evidence suggesting that nuclear architecture and location of specific genetic loci within chromosome territories may influence their participation in intrachromosomal or interchromosomal rearrangements in human thyroid cells.
TL;DR: This is the first large chromosome microdissection/FISH study of chromosome 19 markers in ovarian carcinomas and shows that many chromosomes added material to chromosome 19, but the chromosome arms 11q, 21q, and 22q were particularly common donors.
Abstract: Alterations of chromosome bands 19p13 and 19q13 in the form of added extra material of unknown origin are among the most frequent cytogenetic changes in ovarian carcinomas. To investigate the chromosomal composition of the 19p+ and/or 19q+ markers, we selected for examination 26 ovarian carcinomas which by G-banding had one to four 19p+ and/or 19q+, in total 37 markers. These cases were then subjected to chromosomal microdissection with subsequent reverse painting, which gave informative results on 29 markers. The breakpoints on chromosome 19 were located in both the short (p; n = 15) and the long (q; n = 10) arms, as well as in the centromeric (n = 2) and pericentromeric (n = 6) region. The analysis showed that many chromosomes added material to chromosome 19, but the chromosome arms 11q, 21q, and 22q were particularly common donors. Homogeneously staining regions (hsr) were seen in only three markers, in all of them consisting of 19p material. Eighteen markers were derived from an unbalanced translocation involving chromosome 19. In five markers, chromosome 19 was rearranged with two chromosomes. The most complex marker showed chromosome 19 rearranged with three other chromosomes, i.e., X, 13, and 16. In five markers, all of the additional material stemmed from chromosome 19 itself. This is the first large chromosome microdissection/FISH study of chromosome 19 markers in ovarian carcinomas. A detailed map of the rearrangements should provide clues to the positions of oncogenes and potential fusion genes important in ovarian carcinogenesis.
TL;DR: A novel disease-causing mutation S31W in CRYBB2 was identified in a Chinese cataract family, the first reported mutation for coronary cataracts, and a lipocalin signature motif was predicted by ScanProsite.
Abstract: To study the molecular pathogenesis of a Chinese family with coronary form of cataract. One Chinese three-generation family with inherited coronary cataract phenotype was recruited. Five affected and seven unaffected family members attended our study. Genome-wide linkage analysis was applied to map the disease loci, and two candidate genes from a locus on chromosome 1 and a locus on chromosome 22 were sequenced for mutation identification. Software at the Expasy proteomics server was utilized to predict the mutation effect on proteins. Whole genome linkage analysis indicated some regions on chromosome 1, 10, and 22, with LOD score values greater than 1. Within these loci, the GJA8 and CRYBB2 genes, located in the two loci with the highest LOD score of 1.51 on chromosomes 1 and 22, respectively, were sequenced. A novel mutation c.92C>G in exon 2 of CRYBB2 causing S31W was identified in all five patients. It was not found in 95 unrelated controls. This missense sequence alteration likely enhanced the local solubility. Around the mutation site, a lipocalin signature motif was predicted by ScanProsite. A novel disease-causing mutation S31W in CRYBB2 was identified in a Chinese cataract family. It is the first reported mutation for coronary cataract. Functional characterization should be carried out to evaluate the biological effects of this mutant.
TL;DR: It is demonstrated that of active mechanisms of heterochromatin amplification occurred and were accompanied by chromosomal rearrangements giving rise to the multiple XX/XY1Y2 chromosome systems observed in Rumex species.
Abstract: Rumex papillaris Boiss, & Reut., an Iberian endemic, belongs to the section Acetosa of the genus Rumex whose main representative is R. acetosa L., a species intensively studied in relation to sex-chromosome evolution. Here, we characterize cytogenetically the chromosomal complement of R. papillaris in an effort to enhance future comparative genomic approaches and to better our understanding of sex chromosome structure in plants. Rumex papillaris, as is common in this group, is a dioecious species characterized by the presence of a multiple sex chromosome system (with females 2n = 12 + XX and males 2n = 12 + XY1Y2). Except for the X chromosome both Y chromosomes are the longest in the karyotype and appear heterochromatic due to the accumulation of at least two satellite DNA families, RAE180 and RAYSI. Each chromosome of pair VI has an additional major heterochromatin block at the distal region of the short arm. These supernumerary heterochromatic blocks are occupied by RAE730 satellite DNA family. The Y-related RAE180 family is also present in an additional minor autosomal locus. Our comparative study of the chromosomal organization of the different satellite-DNA sequences in XX/XY and XX/XY1Y2Rumex species demonstrates that of active mechanisms of heterochromatin amplification occurred and were accompanied by chromosomal rearrangements giving rise to the multiple XX/XY1Y2 chromosome systems observed in Rumex. Additionally, Y1 and Y2 chromosomes have undergone further rearrangements leading to differential patterns of Y-heterochromatin distribution between Rumex species with multiple sex chromosome systems.
TL;DR: The cytogenetic characterization and chromosomal DNA content analyses evidenced that C. canephora is a possible progenitor of C. arabica and is a true allotetraploid originated from a cross between Coffea diploid species.
Abstract: Nuclear genome size has been measured in various plants, seeing that knowledge of the DNA content is useful for taxonomic and evolutive studies, plant breeding programs and genome sequencing projects. Besides the nuclear DNA content, tools and protocols to quantify the chromosomal DNA content have been also applied, expanding the data about genomic structure. This study was conducted in order to calculate the Coffea canephora and Coffea arabica chromosomal DNA content, associating cytogenetic methodologies with flow cytometry (FCM) and image cytometry (ICM) tools. FCM analysis showed that the mean nuclear DNA content of C. canephora and C. arabica is 2C = 1.41 and 2.62 pg, respectively. The cytogenetic methodology provided prometaphase and metaphase cells exhibiting adequate chromosomes for the ICM measurements and karyogram assembly. Based on cytogenetic, FCM and ICM results; it was possible to calculate the chromosomal DNA content of the two species. The 1C chromosomal DNA content of C. canephora ranged from 0.09 (chromosome 1) to 0.05 pg (chromosome 11) and C. arabica from 0.09 (chromosome 1) to 0.03 pg (chromosome 22). The methodology presented in this study was suitable for DNA content measuring of each chromosome of C. canephora and C. arabica. The cytogenetic characterization and chromosomal DNA content analyses evidenced that C. arabica is a true allotetraploid originated from a cross between Coffea diploid species. Besides, the same analyses also reinforce that C. canephora is a possible progenitor of C. arabica.
TL;DR: It is assumed that haploinsufficiency or alternative pathomechanisms underlie chromosome 22 aberrations in T-PLL.