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Results for “Chromosome segmentation”

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PubMed2006

Extended tracts of homozygosity in outbred human populations.

Long tracts of consecutive homozygous single nucleotide polymorphisms (SNPs) can arise in the genome through a number of mechanisms. These include inbreeding in which an individual inherits chromosomal segments that are identical by descent from each parent. However, recombination and other processes break up chromosomal segments over generations. The longest tracts are therefore to be expected in populations with an appreciable degree of inbreeding. We examined the length, number and distribution of long tracts of homozygosity in the apparently outbred HapMap populations. We observed 1393 tracts exceeding 1 Mb in length among the 209 unrelated HapMap individuals. The longest was an uninterrupted run of 3922 homozygous SNPs spanning 17.9 Mb in a Japanese individual. We find that homozygous tracts are significantly more common in regions with high linkage disequilibrium and low recombination, and the location of tracts is similar across all populations. The Yoruba sample has the fewest long tracts per individual, consistent with a larger number of generations (and hence amount of recombination) since the founding of that population. Our results suggest that multiple-megabase-scale ancestral haplotypes persist in outbred human populations in broad genomic regions which have lower than average recombination rates. We observed three outlying individuals who have exceptionally long and numerous homozygous tracts that are not associated with recombination suppressed areas of the genome. We consider that this reflects a high level of relatedness in their ancestry which is too recent to have been influenced by the local recombination intensity. Possible alternative mechanisms and the implications of long homozygous tracts in the genome are discussed.

Asian People↗

PubMed1977

Mapping of human chromosomal regions related to neoplasia: evidence from chromosomes 1 and 17.

In clonal aberrations leading to an excess or partial excess of chromosome 1, trisomy for bands 1q25-1q32 was noted in the myeloid cells from all of 34 patients who had various disorders such as acute leukemia, polycythemia vera, and myelofibrosis. This was not the result of a particularly fragile site in that region of the chromosome because the break points in reciprocal translocations that involve it occurred almost exclusively in the short arm. Two consistent rearrangements that have been observed in chromosome 17 produced either duplication of the entire long arm or a translocation of the distal portion of the long arm to chromosome 15. The nonrandom chromosomal changes found in hematologic disorders can now be correlated with the gene loci on these chromosomes or chromosomal segments. Seventy-five genes related to various metabolic enzymes have been mapped; it may be significant that chromosomes carrying gene loci related to nucleic acid metabolism are more frequently involved in hematologic disorders (and other malignancies as well) than are gene loci related to intermediary or carbohydrate metabolism. Furthermore, the known virus-human chromosome associations are closely correlated with the chromosomes affected in hematologic disorders. If one of the effects of carcinogens (including viruses) is to activate genes that regulate host cell DNA synthesis, and if translocations or duplications of specific chromosomal segments produce the same effect, then either of these mechanisms might provide the affected cell with a proliferative advantage.

Chromosome Aberrations↗

PubMed1998

Comparative genomics: tracking chromosome evolution in the family ursidae using reciprocal chromosome painting.

The Ursidae family includes eight species, the karyotype of which diverges somewhat, in both chromosome number and morphology, from that of other families in the order Carnivora. The combination of consensus molecular phylogeny and high-resolution trypsin G-banded karyotype analysis has suggested that ancestral chromosomal fissions and at least two fusion events are associated with the development of the different ursid species. Here, we revisit this hypothesis by hybridizing reciprocal chromosome painting probes derived from the giant panda (Ailuropoda melanoleuca), domestic cat (Felis catus), and man (Homo sapiens) to representative bear species karyotypes. Comparative analysis of the different chromosome segment homologies allowed reconstruction of the genomic composition of a putative ancestral bear karyotype based upon the recognition of 39 chromosome segments defined by painting as the smallest conserved evolutionary unit segments (pSCEUS) among these species. The different pSCEUS combinations occurring among modern bear species support and extend the postulated sequence of chromosomal rearrangements and provide a framework to propose patterns of genome reorganization among carnivores and other mammal radiations.

Animals↗

PubMed2000

Refinement of the smallest commonly deleted segment of chromosome 20 in malignant myeloid diseases and development of a PAC-based physical and transcription map.

A deletion of the long arm of chromosome 20, del(20q), is a recurring abnormality in malignant myeloid diseases. In previous studies, we delineated a commonly deleted segment (CDS) of 5 Mb within band 20q12 flanked by D20S206 (proximal) and D20S481 (distal). We have generated a detailed physical map of P1 artificial chromosome (PAC) clones of this interval as well as a transcriptional map. The contig consists of 81 clones to which 152 markers (27 genes, 45 unique expressed sequence tags (ESTs) or UniGenes, 24 polymorphisms, and 56 sequence-tagged sites) have been mapped. Using PAC clones for fluorescence in situ hybridization analysis of myeloid leukemia cells with reciprocal translocations of 20q, or unbalanced rearrangements leading to loss of 20q, we have narrowed the CDS to an approximately 250-kb interval encompassing two overlapping PACs, P201E16 and P29M7 (between EST AA368224 and D20S481). This interval is gene-rich and contains 5 characterized genes, 4 UniGenes, and 9 single ESTs. The development of a transcriptional map and the identification of the smallest CDS will facilitate the molecular cloning of a myeloid leukemia suppressor gene on 20q.

Alleles↗

PubMed1995

Computer image analysis of comparative genomic hybridization.

We describe and evaluate the image-processing and analysis techniques we have developed for the quantitative analysis of comparative genomic hybridization (CGH; Science 258:818, 1992). In a typical CGH application, two genomic DNA samples are simultaneously hybridized to metaphase chromosomes and detected with different fluorochromes. The primary data in CGH are contained in the intensity ratios of the fluorochromes as a function of position on the chromosomes, which reflect variation in DNA copy number ratio between the two DNA samples. Analysis involves chromosome segmentation, intensity normalization, background corrections, and calculation of the fluorescence intensity profiles and the ratio profile along the chromosome's length. Profiles from several copies of the same chromosome in different metaphases are averaged to reduce the noise. Confidence intervals are calculated and displayed for the mean profiles. The techniques were evaluated by examining the variability found in comparisons of two normal genomic DNAs, where the ratio was expected to be constant, and by measuring the ratios obtained for cell lines with cytogenetically documented copy number changes involving several chromosomal segments. The limits of sensitivity of CGH analysis were investigated by simulation. Guidelines for the interpretation of CGH data and indications of areas for future development of the analytical techniques are also presented.

Cell Line↗

PubMed1999

Hybrid zones and the genetic architecture of a barrier to gene flow between two sunflower species.

Genetic analyses of reproductive barriers represent one of the few methods by which theories of speciation can be tested. However, genetic study is often restricted to model organisms that have short generation times and are easily propagated in the laboratory. Replicate hybrid zones with a diversity of recombinant genotypes of varying age offer increased resolution for genetic mapping experiments and expand the pool of organisms amenable to genetic study. Using 88 markers distributed across 17 chromosomes, we analyze the introgression of chromosomal segments of Helianthus petiolaris into H. annuus in three natural hybrid zones. Introgression was significantly reduced relative to neutral expectations for 26 chromosomal segments, suggesting that each segment contains one or more factors that contribute to isolation. Pollen sterility is significantly associated with 16 of these 26 segments, providing a straightforward explanation of why this subset of blocks is disadvantageous in hybrids. In addition, comparison of rates of introgression across colinear vs. rearranged chromosomes indicates that close to 50% of the barrier to introgression is due to chromosomal rearrangements. These results demonstrate the utility of hybrid zones for identifying factors contributing to isolation and verify the prediction of increased resolution relative to controlled crosses.

Alleles↗

PubMed1995

The genomic sequence for Prader-Willi/Angelman syndromes' loci of human is apparently conserved in the great apes.

Chromosomal changes through pericentric inversions play an important role in the origin of species. Certain pericentric inversions are too minute to be detected cytogenetically, thus hindering the complete reconstruction of hominoid phylogeny. The advent of the fluorescence in situ hybridization (FISH) technique has facilitated the identification of many chromosomal segments, even at the single gene level. Therefore the cosmid probe for Prader-Willi (PWS)/Angelman syndrome to the loci on human chromosome 15 [q11-13] is being used as a marker to highlight the complementary sequence in higher primates. We hybridized metaphase chromosomes of chimpanzee (PTR), gorilla (GGO), and orangutan (PPY) with this probe (Oncor) to characterize the chromosomal segments because the nature of these pericentric inversions remains relatively unknown. Our observations suggest that a pericentric inversion has occurred in chimpanzee chromosome (PTR 16) which corresponds to human chromosome 15 at PTR 16 band p11-12, while in gorilla (GGO 15) and orangutan (PPY 16) the bands q11-13 complemented to human chromosome 15 band q11-13. This approach has proven to be a better avenue to characterize the pericentric inversions which have apparently occurred during human evolution. "Genetic" divergence in the speciation process which occurs through "chromosomal" rearrangement needs to be reevaluated and further explored using newer techniques.

Angelman Syndrome↗

PubMed1989

Pure partial trisomy of the short arm of chromosome 5.

We describe a male infant with multiple dysmorphic features who is trisomic for chromosome segment 5p13.32----5p14.2 as a result of recombination aneusomy. His father is a balanced carrier of an inverted insertion of this chromosome segment. The clinical features of this patient are compared with those of other patients with isolated partial 5p trisomy reported in the literature.

Chromosome Banding↗

PubMed2003

Molecular cytogenetic analysis of wheat-barley hybrids using genomic in situ hybridization and barley microsatellite markers.

In the present investigation, genomic in situ hybridization (GISH) and barley microsatellite markers were used to analyse the genome constitution of wheat-barley hybrids from two backcross generations (BC1 and BC2). Two BC1 plants carried 3 and 6 barley chromosomes, respectively, according to GISH data. Additional chromosomal fragments were detected using microsatellites. Five BC2 plants possessed complete barley chromosomes or chromosome segments and six BC2 plants did not preserve barley genetic material. Molecular markers revealed segments of the barley genome with the size of one marker only, which probably resulted from recombination between wheat and barley chromosomes. The screening of backcrossed populations from intergeneric hybrids could be effectively conducted using both genomic in situ hybridization and molecular microsatellite markers. GISH images presented a general overview of the genome constitution of the hybrid plants, while microsatellite analysis revealed the genetic identity of the alien chromosomes and chromosomal segments introgressed. These methods were complementary and provided comprehensive information about the genomic constitution of the plants produced.

Chimera↗

PubMed2002

Comparative M-FISH and CGH analyses in sensitive and drug-resistant human T-cell acute leukemia cell lines.

Cell lines of human T-cell acute lymphoblastic leukemias (T-ALL) have gained high interest for study of mechanisms of cytostatic drug resistance. However, they should also be suited to examine the validity and reliability of molecular cytogenetic techniques in detecting genomic alterations in neoplastic cells. Therefore, comparative genomic hybridization (CGH) and 24-color-fluorescence-in-situ-hybridization (M-FISH) were applied to eight sublines of CCRF-CEM leukemia cells selected in vitro for drug resistance and to their drug-sensitive parental counterparts. All cell lines were characterized by altered chromosome numbers and by a variety of chromosomal structural aberrations as shown by M-FISH. The great majority of anomalies detected by this technique were confirmed by CGH. Interestingly, a considerable number of the rearrangements found were imbalanced. Amplifications of 5q13 in the six methotrexate-resistant cell lines, a del(9)(p21pter) in all lines examined, and a gain of chromosome 20 in 9 of the 10 lines examined were readily detected by both techniques. The same held true for losses of chromosomes 17 and 18 in the near tetraploid cell lines which could also be confirmed by CGH. Some imbalances of genomic material detected by CGH were, however, not observed by means of M-FISH, possibly due to the limited extension of the corresponding chromosomal segment involved or the small subpopulation of cells affected. On the other hand, reciprocal translocations, balanced isochromosomes, and small deletions remained mainly undetected by CGH. A comparison of chromosomal alterations in drug-resistant and parental cell lines showed not only amplifications of chromosomal segments harboring well-known drug resistance genes, e.g., the dihydrofolate reductase gene, but also chromosomal changes which may involve novel genes associated with drug resistance. Thus, the present study has clearly unveiled the strengths and weaknesses of both techniques which can excellently complement each other. Their combination allowed a distinct improvement of the definition of the complex karyotypes of drug-resistant cell lines.

Chromosome Aberrations↗

PubMed1982

The scattered distribution of actin genes in the mouse and human genomes.

A hamster actin cDNA probe was used to localize actin genes on the major components of mouse and human DNAs, namely on the four families of fragments forming the bulk of these genomes. Over 20 EcoRI fragments hybridizing the probe could be detected; a different subset of these fragments was found in each component. Since the fragment families forming the major components of the mouse and human DNAs derive from very long chromosomal segments, the isochores , the presence of actin genes on all components provides evidence for their dispersion in both genomes. In situ hybridization of 125I-labeled probe to metaphase chromosomes in the presence of dextran sulfate confirmed this dispersion by showing that the 29-30 actin gene sites so identified are distributed on almost all chromosomes. Moreover, some human actin genes could be mapped on specific chromosomal segments; in particular, one gene was localized on the long arm of the X chromosome. Finally, three different mouse actin genes were isolated from a recombinant DNA library and previously investigated interspersed repeated sequences were identified in the vicinity of these genes.

Actins↗

PubMed2005

The pattern of chromosome folding in interphase is outlined by the linear gene density profile.

Spatial organization of chromatin in the interphase nucleus plays a role in gene expression and inheritance. Although it appears not to be random, the principles of this organization are largely unknown. In this work, we show an explicit relationship between the intranuclear localization of various chromosome segments and the pattern of gene distribution along the genome sequence. Using a 7-megabase-long region of the Drosophila melanogaster chromosome 2 as a model, we observed that the six gene-poor chromosome segments identified in the region interact with components of the nuclear matrix to form a compact stable cluster. The six gene-rich segments form a spatially segregated unstable cluster dependent on nonmatrix nuclear proteins. The resulting composite structure formed by clusters of gene-rich and gene-poor regions is reproducible between the nuclei. We suggest that certain aspects of chromosome folding in interphase are predetermined and can be inferred through in silico analysis of chromosome sequence, using gene density profile as a manifestation of "folding code."

Animals↗

PubMed1988

Genetics of susceptibility to 6-aminonicotinamide-induced cleft palate in the mouse: studies in congenic and recombinant inbred strains.

In a search for genetic differences in susceptibility to cleft palate, congenic and recombinant inbred strains of mice were treated with 6-aminonicotinamide or control injections. Of six loci tested, only the chromosome segment marked by N-acetyl transferase was found to affect susceptibility to 6-aminonicotinamide-induced cleft palate. This chromosome segment is known to affect glucocorticoid-induced cleft palate and phenytoin-induced cleft lip with or without cleft palate in these strains of mice.

6-Aminonicotinamide↗

PubMed1990

Rapid two-stage polymerase chain reaction amplification of chromosomal DNA segments in lysates made from monolayer cultures attached to microcarrier beads.

We describe a method for the rapid two-stage amplification and detection by ethidium bromide staining of chromosomal nucleotide (nt) sequences in lysates made directly from anchorage-dependent cells attached to microcarrier beads. The procedure circumvents the need for cell detachment steps prior to analysis, facilitates the collection, transfer, and manipulation of the cells being studied, and makes unnecessary the use of Southern-blot hybridization for identification of specific nt sequences present in a small fraction of cells within a heterogeneous population.

Animals↗

PubMed1976

The relationship of a specific chromosomal region to the development of the acrosome.

In early spermatids of Urodeles the chromosome segments bearing constitutive heterochromatin are localized in one half of the round nucleus; this region becomes the basal part of the long nucleus of the spermatozoon. The euchromatic chromosome segments extend toward the anterior nuclear pole in a bouquet configuration (Macgregor and Walker, 1973). In the course of spermiohistogenesis, one of the heterochromatic regions (the acrosomal chromocenter) migrates from the basal part to the anterior half of the spermatid nucleus. This heterochromatic block is identical with a species-specific, definite C-band in the karyotype. This relationship between the acrosomal chromocenter and a specific chromosomal C-band was established in Triturus cristatus, T. marmoratus, T. alpestric and Cynops pyrrhogaster. In closely related species this particular C-band lies on similar chromosomes. - While the spermatid nucleus still retains its round shape the acrosomal chromocenter despiralizes into a long heterochromatic thread (acrosomal thread). Precisely at the position of this thread the nucleus evaginates and acquires a pear-like shape. During the elongation of the nuclear protrusion the acrosomal thread remains associated with the anterior end. At termination of spermiogenesis it lies closely below the acrosome in the tip of the spermatozoon. Spontaneous aberrations which affect the acrosomal chromocenter or the thread lead to the development of spermatozoa with defective tips. - Several euchromatic segments, interspersed between the heterchromatic segments, can be recognized in the completely despiralized acrosomal thread. Genes responsible for the morphogenetic activities of both, the acrosomal chromocenter and the acrosomal thread, in the development of the spermtip, might be localized in these interspersed euchromatic segments. The existence in higher vertebrates of an acrosomal chromocenter or an equivalent chromosomal region is discussed.

Acrosome↗

PubMed1990

Mapping of insertion element IS5 in the Escherichia coli K-12 chromosome. Chromosomal rearrangements mediated by IS5.

We identified phage clones containing insertion element IS5 in a set of 476 lambda phage clones carrying chromosomal segments that cover almost the entire chromosome of Escherichia coli K-12 W3110. Precise locations and orientations of IS5 were then determined by cleavage analysis of phage DNAs containing them. We mapped 23 copies of IS5 (named is5A to is5W) on the W3110 chromosome. Among them, ten were identified as the common elements present at the same locations in both chromosomes of W3110 and another E. coli K-12 strain, JE5519. While most of the mapped IS5 elements were scattered over the W3110 chromosome, four copies of IS5 (designated is5L, is5M, is5N and is5O) were in a region representing tandem duplication of a DNA segment flanked by two copies of IS5. Interestingly, one unit of this DNA segment as well as a portion of it was seen also in a tandem array in a different region where two copies of IS5 (designated is5P and is5Q) were present. In particular two pairs of the mapped IS5 elements may have been involved in inversion of the chromosomal segments in two of the E. coli K-12 derivatives.

Bacteriophage lambda↗

PubMed1993

Clonal chromosome abnormalities in human breast carcinomas. II. Thirty-four cases with metastatic disease.

Cytogenetic analysis was performed on a selected series of short-term cultures from 34 patients with documented metastatic breast carcinoma. The majority of tumor cells were hyperdiploid, with clonal structural alterations observed in 94% of patients (32/34). The most common numeric changes were -2, -15, and -18. Chromosome 20 was the most frequently over-represented (in near-3n tumors only). Clonal structural chromosome alterations included isochromosomes, terminal deletions, and, most frequently, unbalanced non-reciprocal translocations. Chromosomes most often involved in structural rearrangements included 1, 7, 11, and 6 (accounting for 24.7%, 10.3%, 9.1%, and 7.0% of breakpoints, respectively). When the breakpoints of clonal structural abnormalities were analyzed, they were shown to cluster to several chromosome segments, including 1p11-q21, 7pter, 11p12-q12, and 6q11-21. An analysis of the net gain or loss of specific chromosome segments was also performed, with the most consistent tendency observed being the over-representation of 1q, 6p, 7, and 11. The most frequent losses included 1p, 6q, 7, and 11q.

Adult↗

PubMed1996

Physical and topographical mapping among Triticeae chromosomes.

Three principal approaches have been used in our laboratory to analyze Triticeae genomes. (i) Synteny analysis: synteny among different Gramineae genomes was studied employing the elegant system of the Agropyron chromosome-induced deletion lines of wheat. Deletion mapping, predominantly of the homoeologous group 7 chromosomes, has led to the construction of a high density physical consensus map of wheat. The integration of wheat, barley and oat RFLP markers proves the colinearity between the wheat A-, B- and D-genomes, the H-genome of barley, and the E-genome of Agropyron. (ii) Light microscopic in situ techniques: the recent improvement of a drop technique for plant protoplasts was crucial for the sensitivity enhancement of fluorescence in situ hybridization (FISH), the efficient preparation of plant chromosomes for high resolution scanning electron microscopy, mapping of low-copy sequences, and comparative in situ hybridization. A tandemly amplified repetitive sequence element from microdissected barley chromosomes has enabled the karyotyping of Gramineae genomes in a single step. We have isolated and characterized members of this element family from other Triticeae species using PCR. The significant interspecific sequence differences were useful to identify single plant genomes, chromosomes and chromosome segments via post-hybridization washes under different stringency conditions. These sequences are also useful for simultaneous double or triple hybridization experiments in an attempt to localize new sequences on specific chromosomes or chromosome segments. The physical mapping of the Sec-1 locus has been refined on the satellite of chromosome 1R of rye, and the syntenic locus on barley chromosome 1H was identified. (iii) Physical mapping of rDNA sequences by high resolution electron microscopy: a method was developed for in situ hybridization and signal detection using high resolution field emission scanning electron microscopy and a backscattered electron detector. Colloidal gold particles were localized on chromosome structures resembling the 30 nm fibre. An rDNA probe was located in the secondary constriction and the highly compact adjacent regions of barley chromosomes.

Chromosome Mapping↗