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Sample records for chromosomal regions involved

  1. Integrated map of the chromosome 8p12-p21 region, a region involved in human cancers and Werner syndrome

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    Imbert, A.; Chaffanet, M.; Birnbaum, D.; Pebusque, M.J. [INSERM, Marseille (France)] [and others

    1996-02-15

    This article discusses the genetic mapping of the specific region on human chromosome 8, 8p12-p21, and its implications to human hereditary cancers and diseases. The localization of disease genes such as NEFL and FGFR1 are given, accomplished using contigs which span the region of deletion involved in these hereditary diseases. 59 refs., 4 figs., 3 tabs.

  2. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole;

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1......Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated......-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We...

  3. The evolution of vertebrate somatostatin receptors and their gene regions involves extensive chromosomal rearrangements

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    Ocampo Daza Daniel

    2012-11-01

    Full Text Available Abstract Background Somatostatin and its related neuroendocrine peptides have a wide variety of physiological functions that are mediated by five somatostatin receptors with gene names SSTR1-5 in mammals. To resolve their evolution in vertebrates we have investigated the SSTR genes and a large number of adjacent gene families by phylogeny and conserved synteny analyses in a broad range of vertebrate species. Results We find that the SSTRs form two families that belong to distinct paralogons. We observe not only chromosomal similarities reflecting the paralogy relationships between the SSTR-bearing chromosome regions, but also extensive rearrangements between these regions in teleost fish genomes, including fusions and translocations followed by reshuffling through intrachromosomal rearrangements. These events obscure the paralogy relationships but are still tractable thanks to the many genomes now available. We have identified a previously unrecognized SSTR subtype, SSTR6, previously misidentified as either SSTR1 or SSTR4. Conclusions Two ancestral SSTR-bearing chromosome regions were duplicated in the two basal vertebrate tetraploidizations (2R. One of these ancestral SSTR genes generated SSTR2, -3 and -5, the other gave rise to SSTR1, -4 and -6. Subsequently SSTR6 was lost in tetrapods and SSTR4 in teleosts. Our study shows that extensive chromosomal rearrangements have taken place between related chromosome regions in teleosts, but that these events can be resolved by investigating several distantly related species.

  4. Involvement of regions of the 4th and 7th chromosomes in the open-field activity of mice.

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    Clément, Y; Martin, B; Venault, P; Chapouthier, G

    1995-09-01

    Reactivity to a new environment was studied in mice, using an open-field procedure in two strains, C57BL/6By and ABP/Le, the F1 populations and the intercrosses F2 and backcross segregating populations. The analysis of the behavioral traits: peripheral and central activities, leaning, rearing and defecation in the parental strains made it possible to show that the ABP/Le strain was more reactive than C57BL/6By. In addition, the study of segregating, for four phenotypic markers, in F2 and backcross populations strongly suggested that two autosomal regions were involved in the control of open-field behavior: one in chromosomal region comprising the b locus on chromosome 4 and one in chromosomal region comprising the p locus on chromosome 7.

  5. Chromosomal instability in Streptomyces avermitilis: major deletion in the central region and stable circularized chromosome

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    Wen Ying

    2010-07-01

    Full Text Available Abstract Background The chromosome of Streptomyces has been shown to be unstable, frequently undergoing gross chromosomal rearrangements. However, the mechanisms underlying this phenomenon remain unclear, with previous studies focused on two chromosomal ends as targets for rearrangements. Here we investigated chromosomal instability of Streptomyces avermitilis, an important producer of avermectins, and characterized four gross chromosomal rearrangement events, including a major deletion in the central region. The present findings provide a valuable contribution to the mechanistic study of genetic instability in Streptomyces. Results Thirty randomly-selected "bald" mutants derived from the wild-type strain all contained gross chromosomal rearrangements of various types. One of the bald mutants, SA1-8, had the same linear chromosomal structure as the high avermectin-producing mutant 76-9. Chromosomes of both strains displayed at least three independent chromosomal rearrangements, including chromosomal arm replacement to form new 88-kb terminal inverted repeats (TIRs, and two major deletions. One of the deletions eliminated the 36-kb central region of the chromosome, but surprisingly did not affect viability of the cells. The other deletion (74-kb was internal to the right chromosomal arm. The chromosome of another bald mutant, SA1-6, was circularized with deletions at both ends. No obvious homology was found in all fusion sequences. Generational stability analysis showed that the chromosomal structure of SA1-8 and SA1-6 was stable. Conclusions Various chromosomal rearrangements, including chromosomal arm replacement, interstitial deletions and chromosomal circularization, occurred in S. avermitilis by non-homologous recombination. The finding of an inner deletion involving in the central region of S. avermitilis chromosome suggests that the entire Streptomyces chromosome may be the target for rearrangements, which are not limited, as previously

  6. Auditory function in the Tc1 mouse model of down syndrome suggests a limited region of human chromosome 21 involved in otitis media.

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    Stephanie Kuhn

    Full Text Available Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21 in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K(+ currents characteristic of control hair cells. However, the size of the large conductance (BK Ca(2+ activated K(+ current (I(K,f, which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active.

  7. Organization of the R chromosome region in maize. Triennial report

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    Kermicle, J.L.

    1979-12-01

    Anthocyanin pigmentation in maize is strain and tissue specific. The primary source of variation is represented in maize races indigenous to widely separated geographic regions of North and South America. Secondary sources include variants which have appeared spontaneously in culture, arose following mutagenic treatment, or were incited through paramutation or by means of controlling elements. Much of the observed variation is attributable to a narrowly restricted segment of chromosome 10, designated the R region. The studies on R organization seek to analyze this variation in terms of the number, kind and arrangement of the components involved.

  8. Regional deletion and amplification on chromosome 6 in a uveal melanoma case without abnormalities on chromosomes 1p, 3 and 8.

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    van Gils, Walter; Kilic, Emine; Brüggenwirth, Hennie T; Vaarwater, Jolanda; Verbiest, Michael M; Beverloo, Berna; van Til-Berg, Marjan E; Paridaens, Dion; Luyten, Gregorius P; de Klein, Annelies

    2008-02-01

    Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Loss of the long arm and gain of the short arm of chromosome 6 are frequently observed chromosomal aberrations in UM, together with loss of chromosome 1p36, loss of chromosome 3 and gain of chromosome 8. This suggests the presence of one or more oncogenes on 6p and tumor suppressor genes at 6q that are involved in UM development. Both regions, however, have not been well defined yet. Furthermore in other neoplasms gain of 6p and loss of 6q are frequently occurring events. In this case report, we describe the delineation of a partial gain on chromosome 6p and a partial deletion on 6q in a UM with the objective to pinpoint smaller candidate regions on chromosome 6 involved in UM development. Conventional cytogenetics, comparative genomic hybridization (CGH) and fluorescence in-situ hybridization (FISH) were used to delineate regions of loss and gain on chromosome 6 in this UM patient. With conventional cytogenetics a deleted region was found on chromosome 6q that was further delineated to a region ranging from 6q16.1 to 6q22 using CGH and FISH. A region of gain from 6pter to 6p21.2 was also demarcated with CGH and FISH. No other deletions or amplifications on recurrently involved chromosomes were found in this patient. This study indicates the presence of one or more tumor suppressor genes on chromosomal region 6q16.1-6q22 and the presence of one or more oncogenes on chromosomal region 6pter-6p21.2, which are likely to be important in UM and other tumors.

  9. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.

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    Liu, Pengfei; Erez, Ayelet; Nagamani, Sandesh C Sreenath; Dhar, Shweta U; Kołodziejska, Katarzyna E; Dharmadhikari, Avinash V; Cooper, M Lance; Wiszniewska, Joanna; Zhang, Feng; Withers, Marjorie A; Bacino, Carlos A; Campos-Acevedo, Luis Daniel; Delgado, Mauricio R; Freedenberg, Debra; Garnica, Adolfo; Grebe, Theresa A; Hernández-Almaguer, Dolores; Immken, LaDonna; Lalani, Seema R; McLean, Scott D; Northrup, Hope; Scaglia, Fernando; Strathearn, Lane; Trapane, Pamela; Kang, Sung-Hae L; Patel, Ankita; Cheung, Sau Wai; Hastings, P J; Stankiewicz, Paweł; Lupski, James R; Bi, Weimin

    2011-09-16

    Complex genomic rearrangements (CGRs) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here, we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated, we observed localization and multiple copy number changes including deletions, duplications, and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle.

  10. Hypermethylated Chromosome Regions in Nine Fish Species with Heteromorphic Sex Chromosomes.

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    Schmid, Michael; Steinlein, Claus; Yano, Cassia F; Cioffi, Marcelo B

    2015-01-01

    Sites and amounts of 5-methylcytosine (5-MeC)-rich chromosome regions were detected in the karyotypes of 9 Brazilian species of Characiformes fishes by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. These species, belonging to the genera Leporinus, Triportheus and Hoplias, are characterized by highly differentiated and heteromorphic ZW and XY sex chromosomes. In all species, the hypermethylated regions are confined to constitutive heterochromatin. The number and chromosome locations of hypermethylated heterochromatic regions in the karyotypes are constant and species-specific. Generally, heterochromatic regions that are darkly stained by the C-banding technique are distinctly hypermethylated, but several of the brightly fluorescing hypermethylated regions merely exhibit moderate or faint C-banding. The ZW and XY sex chromosomes of all 9 analyzed species also show species-specific heterochromatin hypermethylation patterns. The analysis of 5-MeC-rich chromosome regions contributes valuable data for comparative cytogenetics of closely related species and highlights the dynamic process of differentiation operating in the repetitive DNA fraction of sex chromosomes.

  11. Robin sequence associated with karyotypic mosaicism involving chromosome 22 abnormalities

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    Salinas, C.F.; Jastrzab, J.M.; Centu, E.S. [Medical Univ. of South Carolina, Charleston, SC (United States)

    1994-09-01

    Robin sequence is characterized by cleft palate, hypoplastic mandible, glossoptosis and respiratory difficulties. The Robin sequence may be observed as an isolated defect or as part of about 33 syndromes; however, to our knowledge, it has never been reported associated with chromosome 22 abnormalities. We examined a two-month-old black boy with a severe case of Robin sequence. Exam revealed a small child with hypoplastic mandible, glossoptosis, high palate and respiratory difficulty with continuous apnea episodes resulting in cyanotic lips and nails. In order to relieve the upper airway obstruction, his tongue was attached to the lower lip. Later a tracheostomy was performed. On follow-up exam, this patient was found to have developmental delay. Cytogenetic studies of both peripheral blood and fibroblast cells showed mosaicism involving chromosome 22 abnormalities which were designated as follows: 45,XY,-22/46,XY,-22,+r(22)/46,XY. Fluorescence in situ hybridization (FISH) studies confirmed the identity of the r(22) and showed the presence of the DiGeorge locus (D22575) but the absence of the D22539 locus which maps to 22q13.3. Reported cases of r(22) show no association with Robin sequence. However, r(22) has been associated with flat bridge of the nose, bulbous tip of the nose, epicanthus and high palate, all characteristics that we also observed in this case. These unusual cytogenetic findings may be causally related to the dysmorphology found in the patient we report.

  12. A Syntenic Region Conserved from Fish to Mammalian X Chromosome

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    Guijun Guan

    2014-01-01

    Full Text Available Sex chromosomes bearing the sex-determining gene initiate development along the male or female pathway, no matter which sex is determined by XY male or ZW female heterogamety. Sex chromosomes originate from ancient autosomes but evolved rapidly after the acquisition of sex-determining factors which are highly divergent between species. In the heterogametic male system (XY system, the X chromosome is relatively evolutionary silent and maintains most of its ancestral genes, in contrast to its Y counterpart that has evolved rapidly and degenerated. Sex in a teleost fish, the Nile tilapia (Oreochromis niloticus, is determined genetically via an XY system, in which an unpaired region is present in the largest chromosome pair. We defined the differences in DNA contents present in this chromosome with a two-color comparative genomic hybridization (CGH and the random amplified polymorphic DNA (RAPD approach in XY males. We further identified a syntenic segment within this region that is well conserved in several teleosts. Through comparative genome analysis, this syntenic segment was also shown to be present in mammalian X chromosomes, suggesting a common ancestral origin of vertebrate sex chromosomes.

  13. Nonrandom involvement of chromosomal segments in human hematologic malignancies

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    Rowley, J. D.

    1977-01-01

    The consistent occurrence of nonrandom chromosome changes in human malignancies suggests that they are not trivial epiphenomena. Whereas we do not understand their significance at present, one possible role which they may fulfill is to provide the chromosomally aberrant cells with a proliferative advantage as the result of alteration of the number and/or location of genes related to nucleic acid biosynthesis. It would be expected that the proliferative advantage provided by various chromosome aberrations differs in patients with different genetic constitutions.

  14. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements

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    Dickson, Laura B.; Sharakhova, Maria V.; Timoshevskiy, Vladimir A.; Fleming, Karen L.; Caspary, Alex; Sylla, Massamba; Black, William C.

    2016-01-01

    was used to identify AT-rich regions, chromomycin A3 following pretreatment with barium hydroxide stained for GC-rich regions and stained the ribosomal RNA locus and YOYO-1 was used to test for differential staining. Chromosome patterns in SenAae strains revealed by these three stains differed from those in IB12. For FISH, 40 BAC clones previously physically mapped on Aaa chromosomes were used to test for chromosome rearrangements in SenAae relative to IB12. Differences in the order of markers identified two chromosomal rearrangements between IB12 and SenAae strains. The first rearrangement involves two overlapping pericentric (containing the centromere) inversions in chromosome 3 or an insertion of a large fragment into the 3q arm. The second rearrangement is close to the centromere on the p arm of chromosome 2. Linkage analysis of the SDL and the white-eye locus identified a likely chromosomal rearrangement on chromosome 1. The reproductive incompatibility observed within SenAae and between SenAae and Aaa may be generally associated with chromosome rearrangements on all three chromosomes and specifically caused by pericentric inversions on chromosomes 2 and 3. PMID:27105225

  15. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements.

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    Dickson, Laura B; Sharakhova, Maria V; Timoshevskiy, Vladimir A; Fleming, Karen L; Caspary, Alex; Sylla, Massamba; Black, William C

    2016-04-01

    used to identify AT-rich regions, chromomycin A3 following pretreatment with barium hydroxide stained for GC-rich regions and stained the ribosomal RNA locus and YOYO-1 was used to test for differential staining. Chromosome patterns in SenAae strains revealed by these three stains differed from those in IB12. For FISH, 40 BAC clones previously physically mapped on Aaa chromosomes were used to test for chromosome rearrangements in SenAae relative to IB12. Differences in the order of markers identified two chromosomal rearrangements between IB12 and SenAae strains. The first rearrangement involves two overlapping pericentric (containing the centromere) inversions in chromosome 3 or an insertion of a large fragment into the 3q arm. The second rearrangement is close to the centromere on the p arm of chromosome 2. Linkage analysis of the SDL and the white-eye locus identified a likely chromosomal rearrangement on chromosome 1. The reproductive incompatibility observed within SenAae and between SenAae and Aaa may be generally associated with chromosome rearrangements on all three chromosomes and specifically caused by pericentric inversions on chromosomes 2 and 3.

  16. [Fluorescence in situ hybridization with DNA probes derived from individual chromosomes and chromosome regions].

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    Bogomolov, A G; Karamysheva, T V; Rubtsov, N B

    2014-01-01

    A significant part of the eukaryotic genomes consists of repetitive DNA, which can form large clusters or distributed along euchromatic chromosome regions. Repeats located in chromosomal regions make a problem in analysis and identification of the chromosomal material with fluorescence in situ hybridization (FISH). In most cases, the identification of chromosome regions using FISH requires detection of the signal produced with unique sequences. The feasibility, advantages and disadvantages of traditional methods of suppression of repetitive DNA hybridization, methods of repeats-free probe construction and methods of chromosome-specific DNA sequences visualization using image processing of multicolor FISH results are considered in the paper. The efficiency of different techniques for DNA probe generation, different FISH protocols, and image processing of obtained microscopic images depends on the genomic size and structure of analyzing species. This problem was discussed and different approaches were considered for the analysis of the species with very large genome, rare species and species which specimens are too small in size to obtain the amount of genomic and Cot-1 DNA required for suppression of repetitive DNA hybridization.

  17. Rapid generation of region-specific probes by chromosome microdissection: Application to the identification of chromosomal rearrangements

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    Trent, J.M.; Guan, X.Y.; Zang, J.; Meltzer, P.S. (Univ. of Michigan, Ann Arbor (United States))

    1993-01-01

    The authors present results using a novel strategy for chromosome microdissection and direct in vitro amplification of specific chromosomal regions, to identify cryptic chromosome alterations, and to rapidly generate region-specific genomic probes. First, banded chromosomes are microdissected and directly PCR amplified by a procedure which eliminates microchemistry (Meltzer, et al., Nature Genetics, 1:24, 1992). The resulting PCR product can be used for several applications including direct labeling for fluorescent in situ hybridization (FISH) to normal metaphase chromosomes. A second application of this procedure is the extremely rapid generation of chromosome region-specific probes. This approach has been successfully used to determine the derivation of chromosome segments unidentifiable by standard chromosome banding analysis. In selected instances these probes have also been used on interphase nuclei and provides the potential for assessing chromosome abnormalities in a variety of cell lineages. The microdissection probes (which can be generated in <24 hours) have also been utilized in direct library screening and provide the possibility of acquiring a significant number of region-specific probes for any chromosome band. This procedure extends the limits of conventional cytogenetic analysis by providing an extremely rapid source of numerous band-specific probes, and by enabling the direct analysis of essentially any unknown chromosome region.

  18. Prenatal diagnosis of chromosome 15 abnormalities in the Prader-Willi/Angelman syndrome region by traditional and molecular cytogenetics

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    Toth-Fejel, S.; Magenis, R.E.; Leff, S. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1995-02-13

    With improvements in culturing and banding techniques, amniotic fluid studies now achieve a level of resolution at which the Prader-Willi syndrome (PWS) and Angelman syndrome (AS) region may be questioned. Chromosome 15 heteromorphisms, detected with Q- and R-banding and used in conjunction with PWS/AS region-specific probes, can confirm a chromosome deletion and establish origin to predict the clinical outcome. We report four de novo cases of an abnormal-appearing chromosome 15 in amniotic fluid samples referred for advanced maternal age or a history of a previous chromosomally abnormal child. The chromosomes were characterized using G-, Q-, and R-banding, as well as isotopic and fluorescent in situ hybridization of DNA probes specific for the proximal chromosome 15 long arm. In two cases, one chromosome 15 homolog showed a consistent deletion of the ONCOR PWS/AS region A and B. In the other two cases, one of which involved an inversion with one breakpoint in the PWS/AS region, all of the proximal chromosome 15 long arm DNA probes used in the in situ hybridization were present on both homologs. Clinical follow-up was not available on these samples, as in all cases the parents chose to terminate the pregnancies. These cases demonstrate the ability to prenatally diagnose chromosome 15 abnormalities associated with PWS/AS. In addition, they highlight the need for a better understanding of this region for accurate prenatal diagnosis. 41 refs., 5 figs.

  19. The gene for calcium-modulating cyclophilin ligand (CAMLG) is located on human Chromosome 5q23 and a syntenic region of mouse chromosome 13

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    Bram, R.J.; Valentine, V.; Shapiro, D.N. [St. Jude Children`s Research Hospital, Memphis, TN (United States)]|[Univ. of Tennessee, Memphis, TN (United States)] [and others

    1996-01-15

    The CAMLG gene encodes a novel cyclophilin B-binding protein called calcium-modulating cyclophilin ligand, which appears to be involved in the regulation of calcium signaling in T lymphocytes and other cells. The murine homolog, Caml, was localized by interspecific backcross analysis in the middle of chromosome 13. By fluorescence in situ hybridization, this gene was localized to human chromosome 5 in a region (q23) known to be syntenic to mouse chromosome 13. These results provide further evidence supporting the extensive homology between human chromosome 5q and mouse chromosome 13. In addition, the results will provide a basis for further evaluation of cytogenetic anomalies that may contribute to inherited defects in calcium signaling or immune system function. 15 refs., 2 figs.

  20. Frequent gene conversion events between the X and Y homologous chromosomal regions in primates

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    Hirai Hirohisa

    2010-07-01

    Full Text Available Abstract Background Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (p-distance between the X and Y chromosomes, depending on the time of recombination arrest. Stratum 4 covers the distal half of the human X chromosome short arm and the p-distance of the stratum is ~10%, on average. However, a 100-kb region, which includes KALX and VCX, in the middle of stratum 4 shows a significantly lower p-distance (1-5%, suggesting frequent sequence exchanges or gene conversions between the X and Y chromosomes in humans. To examine the evolutionary mechanism for this low p-distance region, sequences of a corresponding region including KALX/Y from seven species of non-human primates were analyzed. Results Phylogenetic analysis of this low p-distance region in humans and non-human primate species revealed that gene conversion like events have taken place at least ten times after the divergence of New World monkeys and Catarrhini (i.e., Old World monkeys and hominoids. A KALY-converted KALX allele in white-handed gibbons also suggests a possible recent gene conversion between the X and Y chromosomes. In these primate sequences, the proximal boundary of this low p-distance region is located in a LINE element shared between the X and Y chromosomes, suggesting the involvement of this element in frequent gene conversions. Together with a palindrome on the Y chromosome, a segmental palindrome structure on the X chromosome at the distal boundary near VCX, in humans and chimpanzees, may mediate frequent sequence exchanges between X and Y chromosomes. Conclusion Gene conversion events between the X and Y homologous regions have been suggested, mainly in humans. Here, we found frequent gene conversions in the

  1. Narrowing the genetic interval and yeast artificial chromosome map in the branchio-oto-renal region on chromosome 8q

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    Kumar, Shrawan; Kimberling, W.J.; Pinnt, J. [Boys Town National Research Hospital, Omaha, NE (United States)] [and others

    1996-01-01

    Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by branchial abnormality, hearing loss, and renal anomalies. Recently, the disease gene has been localized to chromosome 8q. Here, we report genetic studies that further refine the disease gene region to a smaller interval and identify several YACs from the critical region. We studied two large, clinically well-characterized BOR families with a set of 13 polymorphic markers spanning the D8S165-D8S275 interval from the chromosome 8q region. Based on multipoint analysis, the highest likelihood for the location of the BOR gene is between markers D8S543 and D8S530, a distance of about 2 cM. YACs that map in the BOR critical region have been identified and characterized by fluorescence in situ hybridization and pulsed-field gel electrophoresis. A YAC contig, based on the STS content map, that covers a minimum of 4 Mb of human DNA in the critical region of BOR is assembled. This lays the groundwork for the construction of a transcriptional map of this region and the eventual identification of genes involved in BOR syndrome. 40 refs., 4 figs., 1 tab.

  2. Molecular mapping of the Edwards syndrome phenotype to two noncontiguous regions on chromosome 18

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    Boghosian-Sell, L.; Mewar, R.; Harrison, W.; Shapiro, R.M.; Zackai, E.H.; Carey, J.; Davis-Keppen, L.; Hudgins, L.; Overhauser, J.

    1994-09-01

    In an effort to identify regions on chromosome 18 that may be critical in the appearance of the Edwards syndrome phenotype, the authors have analyzed six patients with partial duplication of chromosome 18. Four of the patients have duplications involving the distal half of 18q (18q21.1-qter) and are very mildly affected. The remaining two patients have most of 18q (18q12.1-qter) duplicated, are severely affected, and have been diagnosed with Edwards syndrome. The authors have employed FISH, using DNA probes from a chromosome 18-specific library, for the precise determination of the duplicated material in each of these patients. The clinical features and the extent of the chromosomal duplication in these patients were compared with four previously reported partial trisomy 18 patients, to identify regions of chromosome 18 that may be responsible for certain clinical features of trisomy 18. The comparative analysis confirmed that there is no single region on 18q that is sufficient to produce the trisomy 18 phenotype and identified two regions on 18q that may work in conjunction to produce the Edwards syndrome phenotype. In addition, correlative analysis indicates that duplication of 18q12.3-q22.1 may be associated with more severe mental retardation in trisomy 18 individuals. 25 refs., 3 figs., 1 tab.

  3. Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection.

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    Zavattari, P; Deidda, E; Whalen, M; Lampis, R; Mulargia, A; Loddo, M; Eaves, I; Mastio, G; Todd, J A; Cucca, F

    2000-12-12

    Linkage disequilibrium (LD) mapping of disease genes is complicated by population- and chromosome-region-specific factors. We have analysed demographic factors by contrasting intermarker LD results obtained in a large cosmopolitan population (UK), a large genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations therefore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the analysis of chromosome 6p21, including the HLA region. Patterns of global LD in this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes. Subisolate aside, chromosome-region-specific differences in LD patterns appear to be more important than the differences in intermarker LD between distinct populations.

  4. Detection of chromosomal regions showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma

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    Bortoluzzi Stefania

    2004-06-01

    Full Text Available Abstract Background Rhabdomyosarcoma is a relatively common tumour of the soft tissue, probably due to regulatory disruption of growth and differentiation of skeletal muscle stem cells. Identification of genes differentially expressed in normal skeletal muscle and in rhabdomyosarcoma may help in understanding mechanisms of tumour development, in discovering diagnostic and prognostic markers and in identifying novel targets for drug therapy. Results A Perl-code web client was developed to automatically obtain genome map positions of large sets of genes. The software, based on automatic search on Human Genome Browser by sequence alignment, only requires availability of a single transcribed sequence for each gene. In this way, we obtained tissue-specific chromosomal maps of genes expressed in rhabdomyosarcoma or skeletal muscle. Subsequently, Perl software was developed to calculate gene density along chromosomes, by using a sliding window. Thirty-three chromosomal regions harbouring genes mostly expressed in rhabdomyosarcoma were identified. Similarly, 48 chromosomal regions were detected including genes possibly related to function of differentiated skeletal muscle, but silenced in rhabdomyosarcoma. Conclusion In this study we developed a method and the associated software for the comparative analysis of genomic expression in tissues and we identified chromosomal segments showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma, appearing as candidate regions for harbouring genes involved in origin of alveolar rhabdomyosarcoma representing possible targets for drug treatment and/or development of tumor markers.

  5. The human chromosomal fragile sites more often involved in constitutional deletions and duplications - A genetic and statistical assessment

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    Gomes, Dora Prata; Sequeira, Inês J.; Figueiredo, Carlos; Rueff, José; Brás, Aldina

    2016-12-01

    Human chromosomal fragile sites (CFSs) are heritable loci or regions of the human chromosomes prone to exhibit gaps, breaks and rearrangements. Determining the frequency of deletions and duplications in CFSs may contribute to explain the occurrence of human disease due to those rearrangements. In this study we analyzed the frequency of deletions and duplications in each human CFS. Statistical methods, namely data display, descriptive statistics and linear regression analysis were applied to analyze this dataset. We found that FRA15C, FRA16A and FRAXB are the most frequently involved CFSs in deletions and duplications occurring in the human genome.

  6. Detailed comparative map of human chromosome 19q and related regions of the mouse genome

    Energy Technology Data Exchange (ETDEWEB)

    Stubbs, L.; Shannon, M.E.; Kim, Joomyeong [Oak Ridge National Lab., TN (United States)] [and others

    1996-08-01

    One of the larger contiguous blocks of mouse-human genomic homology includes the proximal portion of mouse chromosome 7 and the long arm of human chromosome 19. Previous studies have demonstrated the close relationship between the two regions, but have also indicated significant rearrangements in the relative orders of homologous mouse and human genes. Here we present the genetic locations of the homologs of 42 human chromosome 19q markers in the mouse, with an emphasis on genes also included in the human chromosome 19 physical map. Our results demonstrate that despite an overall inversion of sequences relative to the centromere, apparent {open_quotes}transpositions{close_quotes} of three gene-rich segments, and a local inversion of markers mapping near the 19q telomere, gene content, order, and spacing are remarkably well conserved throughout the lengths of these related mouse and humans regions. Although most human 19q markers have remained genetically linked in mouse, one small human segment forms a separate region of homology between human chromosome 19q and mouse chromosome 17. Three of the four rearrangements of mouse versus human 19q sequences involve segments that are located directly adjacent to each other in 19q13.3-q13.4, suggesting either the coincident occurrence of these events or their common association with unstable DNA sequences. These data permit an unusually in-depth examination of this large region of mouse-human genomic homology and provide an important new tool to aid in the mapping of genes and associated phenotypes in both species. 66 refs., 3 figs., 1 tab.

  7. Regions of XY homology in the pig X chromosome and the boundary of the pseudoautosomal region

    Directory of Open Access Journals (Sweden)

    Skinner Benjamin M

    2013-01-01

    Full Text Available Abstract Background Sex chromosomes are subject to evolutionary pressures distinct from the remainder of the genome, shaping their structure and sequence content. We are interested in the sex chromosomes of domestic pigs (Sus scrofa, how their structure and gene content compares and contrasts with other mammalian species, and the role of sex-linked genes in fertility. This requires an understanding of the XY-homologous sequence on these chromosomes. To this end, we performed microarray-based comparative genomic hybridisation (array-CGH with male and female Duroc genomic DNA on a pig X-chromosome BAC tiling-path microarray. Putative XY-homologous BACs from regions of interest were subsequently FISH mapped. Results We show that the porcine PAR is approximately 6.5-6.9 Mb at the beginning of the short arm of the X, with gene content reflective of the artiodactyl common ancestor. Our array-CGH data also shows an XY-homologous region close to the end of the X long arm, spanning three X BACs. These BACs were FISH mapped, and paint the entire long arm of SSCY. Further clones of interest revealed X-autosomal homology or regions containing repetitive content. Conclusions This study has identified regions of XY homology in the pig genome, and defined the boundary of the PAR on the X chromosome. This adds to our understanding of the evolution of the sex chromosomes in different mammalian lineages, and will prove valuable for future comparative genomic work in suids and for the construction and annotation of the genome sequence for the sex chromosomes. Our finding that the SSCYq repetitive content has corresponding sequence on the X chromosome gives further insight into structure of SSCY, and suggests further functionally important sequences remain to be discovered on the X and Y.

  8. [Chromosomal variation in Chironomus plumosus L. (Diptera, Chironomidae) from populations of Bryansk region, Saratov region (Russia), and Gomel region (Belarus)].

    Science.gov (United States)

    Belyanina, S I

    2015-02-01

    Cytogenetic analysis was performed on samples of Chironomus plumosus L. (Diptera, Chironomidae) taken from waterbodies of various types in Bryansk region (Russia) and Gomel region (Belarus). Karyotypes of specimens taken from stream pools of the Volga were used as reference samples. The populations of Bryansk and Gomel regions (except for a population of Lake Strativa in Starodubskii district, Bryansk region) exhibit broad structural variation, including somatic mosaicism for morphotypes of the salivary gland chromosome set, decondensation of telomeric sites, and the presence of small structural changes, as opposed to populations of Saratov region. As compared with Saratov and Bryansk regions, the Balbiani ring in the B-arm of chromosome I is repressed in populations of Gomel region. It is concluded that the chromosome set of Ch. plumosus in a range of waterbodies of Bryansk and Gomel regions is unstable.

  9. Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes.

    Directory of Open Access Journals (Sweden)

    Kaitlin M Stimpson

    2010-08-01

    Full Text Available Genome rearrangement often produces chromosomes with two centromeres (dicentrics that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extra-chromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.

  10. Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes.

    Science.gov (United States)

    Stimpson, Kaitlin M; Song, Ihn Young; Jauch, Anna; Holtgreve-Grez, Heidi; Hayden, Karen E; Bridger, Joanna M; Sullivan, Beth A

    2010-08-12

    Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extra-chromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.

  11. Chromosome region-specific libraries for human genome analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Fa-Ten.

    1991-01-01

    We have made important progress since the beginning of the current grant year. We have further developed the microdissection and PCR- assisted microcloning techniques using the linker-adaptor method. We have critically evaluated the microdissection libraries constructed by this microtechnology and proved that they are of high quality. We further demonstrated that these microdissection clones are useful in identifying corresponding YAC clones for a thousand-fold expansion of the genomic coverage and for contig construction. We are also improving the technique of cloning the dissected fragments in test tube by the TDT method. We are applying both of these PCR cloning technique to human chromosomes 2 and 5 to construct region-specific libraries for physical mapping purposes of LLNL and LANL. Finally, we are exploring efficient procedures to use unique sequence microclones to isolate cDNA clones from defined chromosomal regions as valuable resources for identifying expressed gene sequences in the human genome. We believe that we are making important progress under the auspices of this DOE human genome program grant and we will continue to make significant contributions in the coming year. 4 refs., 4 figs.

  12. Chromosome

    Science.gov (United States)

    Chromosomes are structures found in the center (nucleus) of cells that carry long pieces of DNA. DNA ... is the building block of the human body. Chromosomes also contain proteins that help DNA exist in ...

  13. Complex Variant of Philadelphia Translocation Involving Chromosomes 9, 12, and 22 in a Case with Chronic Myeloid Leukaemia

    Science.gov (United States)

    Malvestiti, F.; Agrati, C.; Chinetti, S.; Di Meco, A.; Cirrincione, S.; Oggionni, M.; Grimi, B.; Maggi, F.; Simoni, G.; Grati, F. R.

    2014-01-01

    Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph) chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9) may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement. PMID:25045550

  14. Complex Variant of Philadelphia Translocation Involving Chromosomes 9, 12, and 22 in a Case with Chronic Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    F. Malvestiti

    2014-01-01

    Full Text Available Chronic myeloid leukemia (CML is a hematopoietic stem cell disorder included in the broader diagnostic category of myeloproliferative neoplasms, associated with fusion by BCR gene at chromosome 22q11 to ABL1 gene at chromosome 9q34 with the formation of the Philadelphia (Ph chromosome. In 2–10% of CML cases, the fusion gene arises in connection with a variant translocation, involving chromosomes 9, 22, and one or more different chromosomes; consequently, the Ph chromosome could be masked within a complex chromosome rearrangement. In cases with variant Ph translocation a deletion on der(9 may be more frequently observed than in cases with the classical one. Herein we describe a novel case of CML with complex variant Ph translocation involving chromosomes 9, 12, and 22. We present the hematologic response and cytogenetic response after Imatinib treatment. We also speculated the mechanism which had originated the chromosome rearrangement.

  15. Epidemiology of double aneuploidies involving chromosome 21 and the sex chromosomes.

    Science.gov (United States)

    Kovaleva, Natalia V; Mutton, David E

    2005-04-01

    The chance of two chromosome abnormalities occurring in one conceptus is very small. However, some authors have suggested that double aneuplodies (DAs) might be more common than the product of their individual frequencies. The nonrandomness of such DA events was considered to be evidence that nondisjunction (NDJ) may be genetically determined. Data collected from the National Down syndrome Cytogenetic Register (NDSCR) in England and Wales and from the literature indicate that the frequencies of all nonmosaic DAs, except for 48,XXY,+21, are lower than expected, probably because of strong intrauterine selection against such pregnancies. Collectively, we identified 52 cases of nonmosaic 48,XXY,+21; 28 cases of 48,XYY,+21; and 14 cases of 48,XXX,+21 in liveborns and 13 cases of 48,XXY,+21; four cases of 48,XYY,+21; and two cases of 48,XXX,+21 after prenatal diagnoses. Among these cases, analysis of the published unbiased cytogenetic surveys of liveborn DS revealed 24 cases of 48,XXY,+21; nine cases of 48,XYY,+21; and seven cases of 48,XXX,+21. These figures are different from the expected proportion of 1:1:1 (P XYY,+21 DA, with a mean maternal age of 24.7 (P XYY,+21 cases (P genetic predisposition, may play a more important role in the etiology of the most common DA, 48,XXY,+21.

  16. Preferential response of acute myeloid leukemias with translocation involving chromosome 17 to human recombinant granulocyte colony-stimulating factor.

    Science.gov (United States)

    Pébusque, M J; Lafage, M; Lopez, M; Mannoni, P

    1988-07-01

    Induction of proliferation and differentiation in response to the addition of recombinant human granulocyte colony-stimulating factor (G-CSF) was studied by both suspension and semisolid cultures in a series of acute myeloid leukemias (AML). Induction of proliferation by G-CSF alone was observed in six of 27 cases of AML. All acute promyelocytic leukemias with the specific chromosomal translocation t(15;17) and one case of myelomonocytic leukemia with balanced chromosomal translocation involving chromosome 17 at band q12q21 were induced to proliferate strongly by the G-CSF. However, contrary to the long-term proliferative effect observed with granulocyte/macrophage colony-stimulating factor (GM-CSF), G-CSF activity can be characterized by its capability to initiate and promote the growth of responding AML cells but not to sustain long-term proliferation. Finally, no terminal differentiation was found, as assessed by morphology, cytochemistry, and cell surface marker analysis. These results indicate that G-CSF may be sufficient to provide a specific signal for induction of a transient proliferation in AML without induction of terminal differentiation. The cells with the highest response are clonal leukemia cells, all bearing a translocation involving the chromosome region 17q12q21 in which the G-CSF gene has been recently located.

  17. The subtelomeric region is important for chromosome recognition and pairing during meiosis

    Science.gov (United States)

    Calderón, María del Carmen; Rey, María-Dolores; Cabrera, Adoración; Prieto, Pilar

    2014-01-01

    The process of meiosis results in the formation of haploid daughter cells, each of which inherit a half of the diploid parental cells' genetic material. The ordered association of homologues (identical chromosomes) is a critical prerequisite for a successful outcome of meiosis. Homologue recognition and pairing are initiated at the chromosome ends, which comprise the telomere dominated by generic repetitive sequences, and the adjacent subtelomeric region, which harbours chromosome-specific sequences. In many organisms telomeres are responsible for bringing the ends of the chromosomes close together during early meiosis, but little is known regarding the role of the subtelomeric region sequence during meiosis. Here, the observation of homologue pairing between a pair of Hordeum chilense chromosomes lacking the subtelomeric region on one chromosome arm indicates that the subtelomeric region is important for the process of homologous chromosome recognition and pairing. PMID:25270583

  18. Analysis of the terminus region of the Caulobacter crescentus chromosome and identification of the dif site

    DEFF Research Database (Denmark)

    Jensen, Rasmus Bugge

    2006-01-01

    The terminus region of the Caulobacter crescentus chromosome and the dif chromosome dimer resolution site were characterized. The Caulobacter genome contains skewed sequences that abruptly switch strands at dif and may have roles in chromosome maintenance and segregation. Absence of dif or the Xer...

  19. Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication

    OpenAIRE

    Cardone, Maria Francesca; Jiang, Zhaoshi; D'Addabbo, Pietro; Archidiacono, Nicoletta; Rocchi, Mariano; Eichler, Evan E.; Ventura, Mario

    2008-01-01

    Background Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. Results Human bacterial artificial chromosome/p1 artificial ...

  20. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.

    Directory of Open Access Journals (Sweden)

    Qiong Pan

    Full Text Available Complex chromosome rearrangements (CCRs, which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques.

  1. Chromosome alterations in breast carcinomas: frequent involvement of DNA losses including chromosomes 4q and 21q.

    OpenAIRE

    Schwendel, A.; Richard, F.; Langreck, H.; Kaufmann, O.; Lage, H.; Winzer, K.J.; Petersen, I; Dietel, M

    1998-01-01

    Comparative genomic hybridization was applied to map DNA gains and losses in 39 invasive ductal breast carcinomas. Frequent abnormalities included gains on chromosomal regions 1q, 8q, 11q12-13, 16p, 19, 20q and X as well as frequent losses on 1p, 5q, 6q, 9p, 11q, 13q and 16q. Furthermore, frequent losses on 4q (20 cases) and 21q (14 cases) were found for the first time in this tumour type. High copy number amplifications were observed at 8q12-24, 11q11-13 and 20q13-ter. Highly differentiated ...

  2. Methods of Reprogramming to Induced Pluripotent Stem Cell Associated with Chromosomal Integrity and Delineation of a Chromosome 5q Candidate Region for Growth Advantage.

    Science.gov (United States)

    Sobol, Maria; Raykova, Doroteya; Cavelier, Lucia; Khalfallah, Ayda; Schuster, Jens; Dahl, Niklas

    2015-09-01

    Induced pluripotent stem cells (iPSCs) have brought great promises for disease modeling and cell-based therapies. One concern related to the use of reprogrammed somatic cells is the loss of genomic integrity and chromosome stability, a hallmark for cancer and many other human disorders. We investigated 16 human iPSC lines reprogrammed by nonintegrative Sendai virus (SeV) and another 16 iPSC lines generated by integrative lentivirus for genetic changes. At early passages we detected cytogenetic rearrangements in 44% (7/16) of iPSC lines generated by lentiviral integration whereas the corresponding figure was 6% (1/16) using SeV-based delivery. The rearrangements were numerical and/or structural with chromosomes 5 and 12 as the most frequently involved chromosomes. Three iPSC lines with chromosome 5 aberrations were derived from one and the same donor. We present in this study the aberrant karyotypes including a duplication of chromosome 5q13q33 that restricts a candidate region for growth advantage. Our results suggest that the use of integrative lentivirus confers a higher risk for cytogenetic abnormalities at early passages when compared to SeV-based reprogramming. In combination, our findings expand the knowledge on acquired cytogenetic aberrations in iPSC after reprogramming and during culture.

  3. Characterization of FRA7B, a human common fragile site mapped at the 7p chromosome terminal region.

    Science.gov (United States)

    Bosco, Nazario; Pelliccia, Franca; Rocchi, Angela

    2010-10-01

    Common fragile sites (CFS) are specific regions of the mammalian chromosomes that are particularly prone to gaps and breaks. They are a cause of genome instability, and the location of many CFS correlates with breakpoints of aberrations recurrent in some cancers. The molecular characterization of some CFS has not clarified the causes of their fragility. In this work, by using fluorescence in situ hybridization analysis with BAC and PAC clones, we determined the DNA sequence of the CFS FRA7B. The FRA7B sequence was then analyzed to identify coding sequences and some structural features possibly involved in fragility. FRA7B spans about 12.2 megabases, and is therefore one of the largest CFS analyzed. It maps at the 7p21.3-22.3 chromosome bands, therefore at the interface of G- and R-band regions that are probably difficult to replicate. A 90-kilobase long sequence that presents very high flexibility values was identified at the very beginning of the more fragile CFS region. Three large genes (THSD7A, SDK1, and MAD1L1) and two miRNA genes (MIRN589 and MIRN339) map in the fragile region. The chromosome band 7p22 is a recurrent breakpoint in chromosome abnormalities in different types of neoplasm. FRA7B is the first characterized CFS located in a chromosome terminal region.

  4. Construction of a consistent YAC contig for human chromosome region 3p14.1

    NARCIS (Netherlands)

    Bardenheuer, W; Michaelis, S; Lux, A; Vieten, L; Brocker, F; Julicher, K; Willers, C; Siebert, R; Smith, DI; vanderHout, AH; Buys, C; Schutte, J; Opalka, B

    1996-01-01

    Chromosomal deletions and translocations of human chromosome region 3p14 are observed in various human malignancies and suggest the existence of a tumor suppressor gene locus within this region. Tumors most frequently affected by these aberrations are small-cell lung cancer and renal-cell carcinoma.

  5. Topological Organization of Multi-chromosomal Regions by Firre

    Science.gov (United States)

    Hacisuleyman, Ezgi; Goff, Loyal A.; Trapnell, Cole; Williams, Adam; Henao-Mejia, Jorge; Sun, Lei; McClanahan, Patrick; Hendrickson, David G.; Sauvageau, Martin; Kelley, David R.; Morse, Michael; Engreitz, Jesse; Lander, Eric S.; Guttman, Mitch; Lodish, Harvey F.; Flavell, Richard; Raj, Arjun; Rinn, John L.

    2014-01-01

    RNA is known to be an abundant and important structural component of the nuclear matrix, including long noncoding RNAs (lncRNA). Yet the molecular identities, functional roles, and localization dynamics of lncRNAs that influence nuclear architecture remain poorly understood. Here, we describe one lncRNA, Firre, that interacts with the nuclear matrix factor hnRNPU, through a 156 bp repeating sequence and Firre localizes across a ~5 Mb domain on the X-chromosome. We further observed Firre localization across at least five distinct trans-chromosomal loci, which reside in spatial proximity to the Firre genomic locus on the X-chromosome. Both genetic deletion of the Firre locus or knockdown of hnRNPU resulted in loss of co-localization of these trans-chromosomal interacting loci. Thus, our data suggest a model in which lncRNAs such as Firre can interface with and modulate nuclear architecture across chromosomes. PMID:24463464

  6. Pattern of chromosome involvement in childhood hyperdiploid pre-B-cell acute lymhoblastic leukemia cases from India

    Directory of Open Access Journals (Sweden)

    Lily S. Kerketta

    2014-01-01

    Conclusion: In this study, the pattern of chromosome involvement in hyperdiploid karyotype of ALL patients is same as other studies except some chromosomes like 1, 6, 11, 12, 19 and 22 have some more frequent involvement than other studies. This study also showed the occurrence of TEL/AML1 fusion is more (19.8% than other reports from India.

  7. A high-resolution interval map of the q21 region of the human X chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Philippe, C.; Monaco, A.P. [ICRF Laboratories, Oxford (United Kingdom)] [and others; Arnould, C. [Laboratoire de Genetique Humaine, Vandoeuvre-les-Nancy (France)] [and others

    1995-06-10

    In a previous study, we have developed a panel of chromosomal rearrangements for the physical mapping of the q13-q21 region of the human X chromosome. Here, we report the physical localization of 36 additional polymorphic markers by polymerase chain reaction analysis. The high density of chromosomal breakpoints in Xq21 allows us to map 58 DNA loci in 22 intervals. As a result, this segment of the X chromosome is saturated with approximately three sequence tagged sites per megabase of DNA, which will facilitate the construction of a YAC contig of this region. 26 refs., 1 fig., 1 tab.

  8. Interchanges in popcorn (Zea mays L. involving the nucleolus organizer chromosome

    Directory of Open Access Journals (Sweden)

    Maria Suely Pagliarini

    2006-01-01

    Full Text Available The analysis of microsporogenesis in endogamous plants of popcorn (S5 to S7 showed several and distinctinterchanges which involve the nucleolus organizer (chromosome 6. The detection of cells with interchanges was facilitatedby the presence of two nucleoli of different sizes in contrast to normal ones with a single big nucleolus. Interchange points donot always seem to be at the same place. Whereas in several situations the interchange point clearly involved more than twochromosome pairs, a simple terminal translocation seemed to occur in others. During diplotene, a cross-shaped configurationconnected with the nucleoli was observed in some meiocytes. Some heteromorphic bivalents were found during diakinesis,after which meiosis progressed normally to the end and gave rise to apparently normal tetrads with one normal nucleolus ineach microspore. Tests of pollen viability in fixed pollen grains showed 100% stainability in normal and in affected plants.This is the first report on chromosome interchanges in popcorn.

  9. MreB actin-mediated segregation of a specific region of a bacterial chromosome.

    Science.gov (United States)

    Gitai, Zemer; Dye, Natalie Anne; Reisenauer, Ann; Wachi, Masaaki; Shapiro, Lucy

    2005-02-11

    Faithful chromosome segregation is an essential component of cell division in all organisms. The eukaryotic mitotic machinery uses the cytoskeleton to move specific chromosomal regions. To investigate the potential role of the actin-like MreB protein in bacterial chromosome segregation, we first demonstrate that MreB is the direct target of the small molecule A22. We then demonstrate that A22 completely blocks the movement of newly replicated loci near the origin of replication but has no qualitative or quantitative effect on the segregation of other loci if added after origin segregation. MreB selectively interacts, directly or indirectly, with origin-proximal regions of the chromosome, arguing that the origin-proximal region segregates via an MreB-dependent mechanism not used by the rest of the chromosome.

  10. Nonreciprocal chromosomal translocations in renal cancer involve multiple DSBs and NHEJ associated with breakpoint inversion but not necessarily with transcription.

    Science.gov (United States)

    Ali, Hanif; Daser, Angelika; Dear, Paul; Wood, Henry; Rabbitts, Pamela; Rabbitts, Terence

    2013-04-01

    Chromosomal translocations and other abnormalities are central to the initiation of cancer in all cell types. Understanding the mechanism is therefore important to evaluate the evolution of cancer from the cancer initiating events to overt disease. Recent work has concentrated on model systems to develop an understanding of the molecular mechanisms of translocations but naturally occurring events are more ideal case studies since biological selection is absent from model systems. In solid tumours, nonreciprocal translocations are most commonly found, and accordingly we have investigated the recurrent nonreciprocal t(3;5) chromosomal translocations in renal carcinoma to better understand the mechanism of these naturally occurring translocations in cancer. Unexpectedly, the junctions of these translocations can be associated with site-specific, intrachromosomal inversion involving at least two double strand breaks (DSB) in cis and rejoining by nonhomologous end joining or micro-homology end joining. However, these translocations are not necessarily associated with transcribed regions questioning accessibility per se in controlling these events. In addition, intrachromosomal deletions also occur. We conclude these naturally occurring, nonreciprocal t(3;5) chromosomal translocations occur after complex and multiple unresolved intrachromosomal DSBs leading to aberrant joining with concurrent interstitial inversion and that clonal selection of cells is the critical element in cancer development emerging from a plethora of DSBs that may not always be pathogenic.

  11. Interstitial duplications of chromosome region 15q11q13 : Clinical and molecular characterization

    NARCIS (Netherlands)

    Repetto, GR; White, LM; Bader, PJ; Johnson, D; Knoll, JHM

    1998-01-01

    Duplications of chromosome region 15q11q13 often occur as a supernumerary chromosome 15. Less frequently they occur as interstitial duplications [dup(15)]. We describe the clinical and molecular characteristics of three patients with de novo dup(15). The patients, two males and one female (ages 3-21

  12. Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites

    Directory of Open Access Journals (Sweden)

    Pierce Levi CT

    2009-01-01

    Full Text Available Abstract Background Gene rearrangements such as chromosomal translocations have been shown to contribute to cancer development. Human chromosomal fragile sites are regions of the genome especially prone to breakage, and have been implicated in various chromosome abnormalities found in cancer. However, there has been no comprehensive and quantitative examination of the location of fragile sites in relation to all chromosomal aberrations. Results Using up-to-date databases containing all cancer-specific recurrent translocations, we have examined 444 unique pairs of genes involved in these translocations to determine the correlation of translocation breakpoints and fragile sites in the gene pairs. We found that over half (52% of translocation breakpoints in at least one gene of these gene pairs are mapped to fragile sites. Among these, we examined the DNA sequences within and flanking three randomly selected pairs of translocation-prone genes, and found that they exhibit characteristic features of fragile DNA, with frequent AT-rich flexibility islands and the potential of forming highly stable secondary structures. Conclusion Our study is the first to examine gene pairs involved in all recurrent chromosomal translocations observed in tumor cells, and to correlate the location of more than half of breakpoints to positions of known fragile sites. These results provide strong evidence to support a causative role for fragile sites in the generation of cancer-specific chromosomal rearrangements.

  13. 45S rDNA regions are chromosome fragile sites expressed as gaps in vitro on metaphase chromosomes of root-tip meristematic cells in Lolium spp.

    Directory of Open Access Journals (Sweden)

    Jing Huang

    Full Text Available BACKGROUND: In humans, chromosome fragile sites are regions that are especially prone to forming non-staining gaps, constrictions or breaks in one or both of the chromatids on metaphase chromosomes either spontaneously or following partial inhibition of DNA synthesis and have been well identified. So far, no plant chromosome fragile sites similar to those in human chromosomes have been reported. METHODS AND RESULTS: During the course of cytological mapping of rDNA on ryegrass chromosomes, we found that the number of chromosomes plus chromosome fragments was often more than the expected 14 in most cells for Lolium perenne L. cv. Player by close cytological examination using a routine chromosome preparation procedure. Further fluorescent in situ hybridization (FISH using 45S rDNA as a probe indicated that the root-tip cells having more than a 14-chromosome plus chromosome fragment count were a result of chromosome breakage or gap formation in vitro (referred to as chromosome lesions at 45S rDNA sites, and 86% of the cells exhibited chromosome breaks or gaps and all occurred at the sites of 45S rDNA in Lolium perenne L. cv. Player, as well as in L. multiflorum Lam. cv. Top One. Chromatin depletion or decondensation occurred at various locations within the 45S rDNA regions, suggesting heterogeneity of lesions of 45S rDNA sites with respect to their position within the rDNA region. CONCLUSIONS: The chromosome lesions observed in this study are very similar cytologically to that of fragile sites observed in human chromosomes, and thus we conclude that the high frequency of chromosome lesions in vitro in Lolium species is the result of the expression of 45S rDNA fragile sites. Possible causes for the spontaneous expression of fragile sites and their potential biological significance are discussed.

  14. The terminal region of the E. coli chromosome localises at the periphery of the nucleoid

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    Stouf Mathieu

    2011-02-01

    Full Text Available Abstract Background Bacterial chromosomes are organised into a compact and dynamic structures termed nucleoids. Cytological studies in model rod-shaped bacteria show that the different regions of the chromosome display distinct and specific sub-cellular positioning and choreographies during the course of the cell cycle. The localisation of chromosome loci along the length of the cell has been described. However, positioning of loci across the width of the cell has not been determined. Results Here, we show that it is possible to assess the mean positioning of chromosomal loci across the width of the cell using two-dimension images from wide-field fluorescence microscopy. Observed apparent distributions of fluorescent-tagged loci of the E. coli chromosome along the cell diameter were compared with simulated distributions calculated using a range of cell width positioning models. Using this method, we detected the migration of chromosome loci towards the cell periphery induced by production of the bacteriophage T4 Ndd protein. In the absence of Ndd production, loci outside the replication terminus were located either randomly along the nucleoid width or towards the cell centre whereas loci inside the replication terminus were located at the periphery of the nucleoid in contrast to other loci. Conclusions Our approach allows to reliably observing the positioning of chromosome loci along the width of E. coli cells. The terminal region of the chromosome is preferentially located at the periphery of the nucleoid consistent with its specific roles in chromosome organisation and dynamics.

  15. Excess functional copy of allele at chromosomal region 11p15 may cause Wiedemann-Beckwith (EMG) syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, T.; Saitoh, S.; Jinno, Y.; Niikawa, N.; Matsumoto, T. [Nagasaki Univ. School of Medicine (Japan); Narahara, K. [Okayama Univ. School of Medicine, Okayama (Japan); Fukushima, Y. [Saitama Children`s Hospital, Iwatsuki (Japan)

    1994-02-15

    Wiedemann-Beckwith syndrome (WBS) is a genetic disorder with overgrowth and predisposition to Wilms` tumor. The putative locus of the gene responsible for this syndrome is assigned to chromosome region 11p15.5, and genomic imprinting in this region has been proposed: the paternally derived gene(s) at 11p15.5 is selectively expressed, while the maternally transmitted gene(s) is inactive. The authors examined 18 patients for the parental origin of their 11p15 regions. DNA polymorphism analyses using 6 loci on chromosome 11 showed that 2 patients with duplications of 11p15 regions from their respective fathers and one from the mother, indicating the transmission of an excessive paternal gene at 11p15 to each patient. The result, together with the previous findings in karyotypically normal or abnormal patients and in overgrowth mouse experiments, are consistent with imprinting hypothesis that overexpression of paternally derived gene(s) at 11p15.5, probably the human insulin-like growth factor II (IFG-II) gene, may cause the phenotype. Total constitutional uniparental paternal disomy (UPD) or segmental UPD for the 6 loci examined of chromosome 11 was not observed in our 12 sporadic patients. In order to explain completely the inheritance of this syndrome in patients with various chromosomal constitutions, the authors propose an alternative imprinting mechanism involving the other locus that may be paternally imprinted and may suppress the expression of this gene. 28 refs., 3 figs., 1 tab.

  16. Array based characterization of a terminal deletion involving chromosome subband 15q26.2: an emerging syndrome associated with growth retardation, cardiac defects and developmental delay

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    Björkhem Gudrun

    2008-01-01

    Full Text Available Abstract Background Subtelomeric regions are gene rich and deletions in these chromosomal segments have been demonstrated to account for approximately 2.5% of patients displaying mental retardation with or without association of dysmorphic features. However, cases that report de novo terminal deletions on chromosome arm 15q are rare. Methods In this study we present the first example of a detailed molecular genetic mapping of a de novo deletion in involving 15q26.2-qter, caused by the formation of a dicentric chromosome 15, using metaphase FISH and tiling resolution (32 k genome-wide array-based comparative genomic hybridization (CGH. Results After an initial characterization of the dicentric chromosome by metaphase FISH, array CGH analysis mapped the terminal deletion to encompass a 6.48 megabase (Mb region, ranging from 93.86–100.34 Mb on chromosome 15. Conclusion In conclusion, we present an additional case to the growing family of reported cases with 15q26-deletion, thoroughly characterized at the molecular cytogenetic level. In the deleted regions, four candidate genes responsible for the phenotype of the patient could be delineated: IGFR1, MEF2A, CHSY1, and TM2D3. Further characterization of additional patients harboring similar 15q-aberrations might hopefully in the future lead to the description of a clear cut clinically recognizable syndrome.

  17. Syndromal frontonasal dysostosis in a child with a complex translocation involving chromosomes 3, 7, and 11.

    Science.gov (United States)

    Stevens, C A; Qumsiyeh, M B

    1995-02-13

    We report on a 4-year-old boy with typical frontonasal dysostosis and an apparently balanced de novo translocation involving chromosomes 3, 7, and 11, and four breakpoints. The karyotype was 46,XY,t(7;3)(3;11) (7pter-->7q21.3::3q27-->3qter;3pter-->3 q23::11q21-->11qter; 11pter-->11q21::3q23-->3q27::7q21.3-->7 qter). In situ hybridization with a chromosome 3 painting probe confirmed the interpretation from GTG banding. The child had a widow's peak, marked hypertelorism, absence of the nasal tip, and widely separated nares. He also had an atrial septal defect, micropenis, small testes, clubfeet, scoliosis, block C2-4, and structural brain abnormalities on MRI. In review we found two other cases of frontonasal dysostosis with chromosome abnormalities, neither of which was similar to our case. The presence of a de novo (apparently) balanced translocation in our patient may help to locate the gene(s) for frontonasal dysplasia and perhaps other midline craniofacial malformations.

  18. Cryptic mosaicism involving a second chromosome X in patients with Turner syndrome

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    A. Araújo

    2008-05-01

    Full Text Available The high abortion rate of 45,X embryos indicates that patients with Turner syndrome and 45,X karyotype could be mosaics, in at least one phase of embryo development or cellular lineage, due to the need for the other sex chromosome presence for conceptus to be compatible with life. In cases of structural chromosomal aberrations or hidden mosaicism, conventional cytogenetic techniques can be ineffective and molecular investigation is indicated. Two hundred and fifty patients with Turner syndrome stigmata were studied and 36 who had female genitalia and had been cytogenetically diagnosed as having "pure" 45,X karyotype were selected after 100 metaphases were analyzed in order to exclude mosaicism and the presence of genomic Y-specific sequences (SRY, TSPY, and DAZ was excluded by PCR. Genomic DNA was extracted from peripheral blood and screened by the human androgen receptor (HUMARA assay. The HUMARA gene has a polymorphic CAG repeat and, in the presence of a second chromosome with a different HUMARA allele, a second band will be amplified by PCR. Additionally, the CAG repeats contain two methylation-sensitive HpaII enzyme restriction sites, which can be used to verify skewed inactivation. Twenty-five percent (9/36 of the cases showed a cryptic mosaicism involving a second X and approximately 14% (5/36, or 55% (5/9 of the patients with cryptic mosaicism, also presented skewed inactivation. The laboratory identification of the second X chromosome and its inactivation pattern are important for the clinical management (hormone replacement therapy, and inclusion in an oocyte donation program and prognostic counseling of patients with Turner syndrome.

  19. Paralogy mapping: Identification of a region in the human MHC triplicated onto human chromosomes 1 and 9 allows the prediction and isolation of novel PBX and NOTCH loci

    Energy Technology Data Exchange (ETDEWEB)

    Katsanis, N.; Fisher, E.M.C. [Imperial College of Medicine at St. Mary`s, London (United Kingdom); Fitzgibbon, J. [Institute of Ophthalmology, London (United Kingdom)

    1996-07-01

    The human genome contains a group of gene families whose members map within the same regions of chromosomes 1, 6, and 9. The number of gene families involved and their pronounced clustering to the same areas of the genome indicate that their mapping relationship in nonrandom. By combining mapping data and sequence information for the gene families, we have determined that these sequences are part of a large region that spans several megabases. This region is present in three copies: on the long arm of human chromosome 1, the short arm of chromosome 6, and the long arm of chromosome 9. We have characterized the phylogenesis of two of the gene families involved and propose an evolutionary route for the creation of the three regions. Our analysis led us to predict and demonstrate the presence of two loci, a PBX locus on chromosome 6 and a NOTCH locus on chromosome 1. The discovery of this triplicated region increases our understanding of the evolution of the human genome and may have considerable practical implications for gene mapping prediction and novel approaches to isolating new gene family members and uncloned disease loci. 32 refs., 4 figs., 2 tabs.

  20. A new region of conservation is defined between human and mouse X chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Dinulos, M.B.; Disteche, C.M. [Univ. of Washington, Seattle, WA (United States); Bassi, M.T. [Univ. of Siena (Italy)] [and others

    1996-07-01

    Comparative mapping of the X chromosome in eutherian mammals have revealed distinct regions of conservation as well as evolutionary rearrangements between human and mouse. Recently, we and others mapped the murine homologue of CLCN4 (Chloride channel 4) to band F4 of the X chromosome in Mus spretus but to chromosome 7 in laboratory strains. We now report the mapping of the murine homologues of APXL (Apical protein Xenopus laevis-like) and OA1 (Ocular albinism type I), two genes that are located on the human X chromosome at band p22.3 and in close proximity to CLCN4. Interestingly, Oa1 and Apxl map to bands F2-F3 in both M. spretus and the laboratory strain C57BL/6J, defining a new rearrangement between human and mouse X chromosomes. 17 refs., 2 figs., 1 tab.

  1. PCR-based panel for regional localization of genes on chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    McDaniel, L.D.; Zhang, B.; Schultz, R.A. [Univ. of Texas Southwestern Medical Center, Dallas (United States)

    1994-09-01

    As the number of genes mapped to specific human chromosomes continues to increase, the feasibility of identifying the gene involved in a human genetic disease via a `candidate gene` approach will continue to improve. Although fluorescence in situ hybridization offers one approach to achieve refined mapping, results are dependent on the size of the probe used, which is not optimal for cDNAs or ESTs. In contrast, a PCR-based approach can achieve mapping for clones <100 bp in size. Through the use of a previously described deletion of chromosome 15 and the 15/17 translocation common to acute promyelocytic leukemia, we have assembled a small panel of somatic cell hybrids that can be used to assign probes to the regions 15p-q15, 15q15-q22, and 15q22-ter. Primers specific for unique cDNA sequences were used to amplify genomic DNA through the polymerase chain reaction. With this approach, we have assigned hexosaminidase A and aggrecan1 to 15q22-qter and leukocyte tyrosine kinase to 15q15-22.

  2. The nucleoporin Mlp2 is involved in chromosomal distribution during mitosis in trypanosomatids.

    Science.gov (United States)

    Morelle, Christelle; Sterkers, Yvon; Crobu, Lucien; MBang-Benet, Diane-Ethna; Kuk, Nada; Portalès, Pierre; Bastien, Patrick; Pagès, Michel; Lachaud, Laurence

    2015-04-30

    Nucleoporins are evolutionary conserved proteins mainly involved in the constitution of the nuclear pores and trafficking between the nucleus and cytoplasm, but are also increasingly viewed as main actors in chromatin dynamics and intra-nuclear mitotic events. Here, we determined the cellular localization of the nucleoporin Mlp2 in the 'divergent' eukaryotes Leishmania major and Trypanosoma brucei. In both protozoa, Mlp2 displayed an atypical localization for a nucleoporin, essentially intranuclear, and preferentially in the periphery of the nucleolus during interphase; moreover, it relocated at the mitotic spindle poles during mitosis. In T. brucei, where most centromeres have been identified, TbMlp2 was found adjacent to the centromeric sequences, as well as to a recently described unconventional kinetochore protein, in the periphery of the nucleolus, during interphase and from the end of anaphase onwards. TbMlp2 and the centromeres/kinetochores exhibited a differential migration towards the poles during mitosis. RNAi knockdown of TbMlp2 disrupted the mitotic distribution of chromosomes, leading to a surprisingly well-tolerated aneuploidy. In addition, diploidy was restored in a complementation assay where LmMlp2, the orthologue of TbMlp2 in Leishmania, was expressed in TbMlp2-RNAi-knockdown parasites. Taken together, our results demonstrate that Mlp2 is involved in the distribution of chromosomes during mitosis in trypanosomatids.

  3. Genomic hallmarks of genes involved in chromosomal translocations in hematological cancer.

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    Mikhail Shugay

    Full Text Available Reciprocal chromosomal translocations (RCTs leading to the formation of fusion genes are important drivers of hematological cancers. Although the general requirements for breakage and fusion are fairly well understood, quantitative support for a general mechanism of RCT formation is still lacking. The aim of this paper is to analyze available high-throughput datasets with computational and robust statistical methods, in order to identify genomic hallmarks of translocation partner genes (TPGs. Our results show that fusion genes are generally overexpressed due to increased promoter activity of 5' TPGs and to more stable 3'-UTR regions of 3' TPGs. Furthermore, expression profiling of 5' TPGs and of interaction partners of 3' TPGs indicates that these features can help to explain tissue specificity of hematological translocations. Analysis of protein domains retained in fusion proteins shows that the co-occurrence of specific domain combinations is non-random and that distinct functional classes of fusion proteins tend to be associated with different components of the gene fusion network. This indicates that the configuration of fusion proteins plays an important role in determining which 5' and 3' TPGs will combine in specific fusion genes. It is generally accepted that chromosomal proximity in the nucleus can explain the specific pairing of 5' and 3' TPGS and the recurrence of hematological translocations. Using recently available data for chromosomal contact probabilities (Hi-C we show that TPGs are preferentially located in early replicated regions and occupy distinct clusters in the nucleus. However, our data suggest that, in general, nuclear position of TPGs in hematological cancers explains neither TPG pairing nor clinical frequency. Taken together, our results support a model in which genomic features related to regulation of expression and replication timing determine the set of candidate genes more likely to be translocated in

  4. Tissue-specific differences in the spatial interposition of X-chromosome and 3R chromosome regions in the malaria mosquito Anopheles messeae Fall.

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    Gleb Artemov

    Full Text Available Spatial organization of a chromosome in a nucleus is very important in biology but many aspects of it are still generally unresolved. We focused on tissue-specific features of chromosome architecture in closely related malaria mosquitoes, which have essential inter-specific differences in polytene chromosome attachments in nurse cells. We showed that the region responsible for X-chromosome attachment interacts with nuclear lamina stronger in nurse cells, then in salivary glands cells in Anopheles messeae Fall. The inter-tissue differences were demonstrated more convincingly in an experiment of two distinct chromosomes interposition in the nucleus space of cells from four tissues. Microdissected DNA-probes from nurse cells X-chromosome (2BC and 3R chromosomes (32D attachment regions were hybridized with intact nuclei of nurse cells, salivary gland cells, follicle epithelium cells and imaginal disсs cells in 3D-FISH experiments. We showed that only salivary gland cells and follicle epithelium cells have no statistical differences in the interposition of 2BC and 32D. Generally, the X-chromosome and 3R chromosome are located closer to each other in cells of the somatic system in comparison with nurse cells on average. The imaginal disсs cell nuclei have an intermediate arrangement of chromosome interposition, similar to other somatic cells and nurse cells. In spite of species-specific chromosome attachments there are no differences in interposition of nurse cells chromosomes in An. messeae and An. atroparvus Thiel. Nurse cells have an unusual chromosome arrangement without a chromocenter, which could be due to the special mission of generative system cells in ontogenesis and evolution.

  5. Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q.

    Science.gov (United States)

    Geremek, Maciej; Schoenmaker, Frederieke; Zietkiewicz, Ewa; Pogorzelski, Andrzej; Diehl, Scott; Wijmenga, Cisca; Witt, Michal

    2008-06-01

    Primary ciliary dyskinesia (PCD) is a rare genetic disorder, which shows extensive genetic heterogeneity and is mostly inherited in an autosomal recessive fashion. There are four genes with a proven pathogenetic role in PCD. DNAH5 and DNAI1 are involved in 28 and 10% of PCD cases, respectively, while two other genes, DNAH11 and TXNDC3, have been identified as causal in one PCD family each. We have previously identified a 3.5 cM (2.82 Mb) region on chromosome 15q linked to Kartagener syndrome (KS), a subtype of PCD characterized by the randomization of body organ positioning. We have now refined the KS candidate region to a 1.8 Mb segment containing 18 known genes. The coding regions of these genes and three neighboring genes were subjected to sequence analysis in seven KS probands, and we were able to identify 60 single nucleotide sequence variants, 35 of which resided in mRNA coding sequences. However, none of the variations alone could explain the occurrence of the disease in these patients.

  6. Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44.

    Science.gov (United States)

    Nagamani, Sandesh C Sreenath; Erez, Ayelet; Bay, Carolyn; Pettigrew, Anjana; Lalani, Seema R; Herman, Kristin; Graham, Brett H; Nowaczyk, Malgorzata Jm; Proud, Monica; Craigen, William J; Hopkins, Bobbi; Kozel, Beth; Plunkett, Katie; Hixson, Patricia; Stankiewicz, Pawel; Patel, Ankita; Cheung, Sau Wai

    2012-02-01

    Submicroscopic deletions involving chromosome 1q43-q44 result in cognitive impairment, microcephaly, growth restriction, dysmorphic features, and variable involvement of other organ systems. A consistently observed feature in patients with this deletion are the corpus callosal abnormalities (CCAs), ranging from thinning and hypoplasia to complete agenesis. Previous studies attempting to delineate the critical region for CCAs have yielded inconsistent results. We conducted a detailed clinical and molecular characterization of seven patients with deletions of chromosome 1q43-q44. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. Four patients had CCAs, and shared the smallest region of overlap that contains only three protein coding genes, CEP170, SDCCAG8, and ZNF238. One patient with a small deletion involving SDCCAG8 and AKT3, and another patient with an intragenic deletion of AKT3 did not have any CCA, implying that the loss of these two genes is unlikely to be the cause of CCA. CEP170 is expressed extensively in the brain, and encodes for a protein that is a component of the centrosomal complex. ZNF238 is involved in control of neuronal progenitor cells and survival of cortical neurons. Our results rule out the involvement of AKT3, and implicate CEP170 and/or ZNF238 as novel genes causative for CCA in patients with a terminal 1q deletion.

  7. Construction of physical maps for the sex-specific regions of papaya sex chromosomes

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    Na Jong-Kuk

    2012-05-01

    Full Text Available Abstract Background Papaya is a major fruit crop in tropical and subtropical regions worldwide. It is trioecious with three sex forms: male, female, and hermaphrodite. Sex determination is controlled by a pair of nascent sex chromosomes with two slightly different Y chromosomes, Y for male and Yh for hermaphrodite. The sex chromosome genotypes are XY (male, XYh (hermaphrodite, and XX (female. The papaya hermaphrodite-specific Yh chromosome region (HSY is pericentromeric and heterochromatic. Physical mapping of HSY and its X counterpart is essential for sequencing these regions and uncovering the early events of sex chromosome evolution and to identify the sex determination genes for crop improvement. Results A reiterate chromosome walking strategy was applied to construct the two physical maps with three bacterial artificial chromosome (BAC libraries. The HSY physical map consists of 68 overlapped BACs on the minimum tiling path, and covers all four HSY-specific Knobs. One gap remained in the region of Knob 1, the only knob structure shared between HSY and X, due to the lack of HSY-specific sequences. This gap was filled on the physical map of the HSY corresponding region in the X chromosome. The X physical map consists of 44 BACs on the minimum tiling path with one gap remaining in the middle, due to the nature of highly repetitive sequences. This gap was filled on the HSY physical map. The borders of the non-recombining HSY were defined genetically by fine mapping using 1460 F2 individuals. The genetically defined HSY spanned approximately 8.5 Mb, whereas its X counterpart extended about 5.4 Mb including a 900 Kb region containing the Knob 1 shared by the HSY and X. The 8.5 Mb HSY corresponds to 4.5 Mb of its X counterpart, showing 4 Mb (89% DNA sequence expansion. Conclusion The 89% increase of DNA sequence in HSY indicates rapid expansion of the Yh chromosome after genetic recombination was suppressed 2–3 million years ago. The

  8. SCREENING OF PRESENCE OF EXTRA Y CHROMOSOME IN AGGRESSIVE TALL MALES OF NORTH INDIAN REGION

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    Balreet kaur

    2015-09-01

    Full Text Available Background: Aggression has been hypothesised with biological instinctual theory, frustration theory and social learning theory. The biological instinctual theory was based on hereditary factors and is associated with XYY syndrome. Objectives: To find out the presence of extra Y chromosome in aggressive taller males of north Indian region. Materials and Methods: Buss and Perry questionnaire was used to find out the aggression of the subjects. The height was measured with the help of metallic tape. Quinacrine dihydrochloride and Macllvaines Buffer was used to stain the buccal smear slide for the general screening of the number of Y chromosomes. The conventional metaphase was prepared for the confirmation of number of Y chromosomes and the slides were stained with giemsa. Observations: The aggression was found more in taller males and they had no extra Y chromosome. Conclusions: Extra Y chromosome may be the cause of aggression and more height in males. But in the present study of males of north Indian region no extra Y chromosome was found in aggressive and taller males.

  9. Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms.

    Science.gov (United States)

    Fraser, James A; Diezmann, Stephanie; Subaran, Ryan L; Allen, Andria; Lengeler, Klaus B; Dietrich, Fred S; Heitman, Joseph

    2004-12-01

    Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT) loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen Cryptococcus revealed sequential evolutionary events that fashioned this large, highly unusual region. We hypothesize that MAT evolved via four main steps, beginning with acquisition of genes into two unlinked sex-determining regions, forming independent gene clusters that then fused via chromosomal translocation. A transitional tripolar intermediate state then converted to a bipolar system via gene conversion or recombination between the linked and unlinked sex-determining regions. MAT was subsequently subjected to intra- and interallelic gene conversion and inversions that suppress recombination. These events resemble those that shaped mammalian sex chromosomes, illustrating convergent evolution in sex-determining structures in the animal and fungal kingdoms.

  10. Mechanisms for chromosome segregation.

    Science.gov (United States)

    Bouet, Jean-Yves; Stouf, Mathieu; Lebailly, Elise; Cornet, François

    2014-12-01

    Bacteria face the problem of segregating their gigantic chromosomes without a segregation period restricted in time and space, as Eukaryotes do. Segregation thus involves multiple activities, general or specific of a chromosome region and differentially controlled. Recent advances show that these various mechanisms conform to a “pair and release” rule, which appears as a general rule in DNA segregation. We describe the latest advances in segregation of bacterial chromosomes with emphasis on the different pair and release mechanisms.

  11. Saethre-Chotzen syndrome with severe developmental delay associated with deletion of chromosomic region 7p15 --> pter.

    Science.gov (United States)

    Touliatou, V; Mavrou, A; Kolialexi, A; Kanavakis, E; Kitsiou-Tzeli, S

    2007-01-01

    Saethre-Chotzen syndrome represents one of the most common types of craniosynostosis inherited as an autosomal dominant disorder while sporadic cases have also been reported. It is characterized by high penetrance and variable expressivity, leading to difficulties in clinical diagnosis. Some patients, who exhibit most of the diagnostic criteria of Saethre-Chotzen syndrome, have structural abnormalities of chromosome 7. The case of a 4 year old boy with notable dysmorphic features compatible with Saethre-Chotzen syndrome and severe developmental delay is described. Conventional and molecular cytogenetic analysis of peripheral blood samples from the patient and his parents revealed partial monosomy of chromosomal region 7p15 --> pter de novo. The TWIST gene, located on chromosome 7p21.1, is thought to be a negative transcriptional regulator involved in osteoblast differentiation and maturation and it is thought that haploinsufficiency of the gene can cause the disorder. The diagnosis of Saethre-Chotzen syndrome and the identification of the chromosomal abnormality in the patient facilitated genetic counseling of the family.

  12. Copy number variations of chromosome 16p13.1 region associated with schizophrenia

    DEFF Research Database (Denmark)

    Ingason, A; Rujescu, D; Cichon, S

    2011-01-01

    Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients an...... disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia....

  13. Chromosome segregation analysis in human embryos obtained from couples involving male carriers of reciprocal or Robertsonian translocation.

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    Ahmet Yilmaz

    Full Text Available The objective of this study was to investigate the frequency and type of chromosome segregation patterns in cleavage stage embryos obtained from male carriers of Robertsonian (ROB and reciprocal (REC translocations undergoing preimplantation genetic diagnosis (PGD at our reproductive center. We used FISH to analyze chromosome segregation in 308 day 3 cleavage stage embryos obtained from 26 patients. The percentage of embryos consistent with normal or balanced segregation (55.1% vs. 27.1% and clinical pregnancy (62.5% vs. 19.2% rates were higher in ROB than the REC translocation carriers. Involvement of non-acrocentric chromosome(s or terminal breakpoint(s in reciprocal translocations was associated with an increase in the percent of embryos consistent with adjacent 1 but with a decrease in 3∶1 segregation. Similar results were obtained in the analysis of nontransferred embryos donated for research. 3∶1 segregation was the most frequent segregation type in both day 3 (31% and spare (35% embryos obtained from carriers of t(11;22(q23;q11, the only non-random REC with the same breakpoint reported in a large number of unrelated families mainly identified by the birth of a child with derivative chromosome 22. These results suggest that chromosome segregation patterns in day 3 and nontransferred embryos obtained from male translocation carriers vary with the type of translocation and involvement of acrocentric chromosome(s or terminal breakpoint(s. These results should be helpful in estimating reproductive success in translocation carriers undergoing PGD.

  14. Variations of chromosomal structures in Caluromys philander (Didelphimorphia: Didelphidae) from the Amazon region.

    Science.gov (United States)

    Souza, Erica Martinha Silva de; Faresin e Silva, Carlos Eduardo; Eler, Eduardo Schmidt; Silva, Maria Nazareth F da; Feldberg, Eliana

    2013-03-01

    Caluromys is considered to be one of the most ancient genera of extant marsupials and is positioned among the basal taxa of the family Didelphidae. At least two species occur in Brazil, C. philander and C. lanatus, both of which have 2n = 14 chromosomes. For the first time, we present evidence of an intrapopulation polymorphism of the sexual chromosome pair in C. philander females from the Central Amazon region. Detailed cytogenetic results of animals from three localities on the Amazon region were analyzed using classical cytogenetics (NOR, C-Band and G-Band) and molecular techniques (18S rDNA and telomere probes). Similar to other conspecific individuals, the diploid number of these animals is 2n = 14, and their fundamental number is 24, with NOR present on the 6th autosomal pair. The X chromosome presented variation detectable by G banding, suggesting a pericentric inversion.

  15. On the Wegener granulomatosis associated region on chromosome 6p21.3

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    Csernok Elena

    2006-03-01

    Full Text Available Abstract Background Wegener granulomatosis (WG belongs to the heterogeneous group of systemic vasculitides. The multifactorial pathophysiology of WG is supposedly caused by yet unknown environmental influence(s on the basis of genetic predisposition. The presence of anti-neutrophil cytoplasmic antibodies (ANCA in the plasma of patients and genetic involvement of the human leukocyte antigen system reflect an autoimmune background of the disease. Strong associations were revealed with WG by markers located in the major histocompatibility complex class II (MHC II region in the vicinity of human leukocyte antigen (HLA-DPB1 and the retinoid X receptor B (RXRB loci. In order to define the involvement of the 6p21.3 region in WG in more detail this previous population-based association study was expanded here to the respective 3.6 megabase encompassing this region on chromosome 6. The RXRB gene was analysed as well as a splice-site variation of the butyrophilin-like (BTNL2 gene which is also located within the respective region. The latter polymorphism has been evaluated here as it appears as a HLA independent susceptibility factor in another granulomatous disorder, sarcoidosis. Methods 150–180 German WG patients and a corresponding cohort of healthy controls (n = 100–261 were used in a two-step study. A panel of 94 microsatellites was designed for the initial step using a DNA pooling approach. Markers with significantly differing allele frequencies between patient and control pools were individually genotyped. The RXRB gene was analysed for single strand conformation polymorphisms (SSCP and restriction fragment length polymorphisms (RFLP. The splice-site polymorphism in the BTNL2 gene was also investigated by RFLP analysis. Results A previously investigated microsatellite (#1.0.3.7, Santa Cruz genome browser (UCSC May 2004 Freeze localisation: chr6:31257596-34999883, which was used as a positive control, remained associated throughout the whole two

  16. Differentially methylated regions in maternal and paternal uniparental disomy for chromosome 7.

    Science.gov (United States)

    Hannula-Jouppi, Katariina; Muurinen, Mari; Lipsanen-Nyman, Marita; Reinius, Lovisa E; Ezer, Sini; Greco, Dario; Kere, Juha

    2014-03-01

    DNA methylation is a hallmark of genomic imprinting and differentially methylated regions (DMRs) are found near and in imprinted genes. Imprinted genes are expressed only from the maternal or paternal allele and their normal balance can be disrupted by uniparental disomy (UPD), the inheritance of both chromosomes of a chromosome pair exclusively from only either the mother or the father. Maternal UPD for chromosome 7 (matUPD7) results in Silver-Russell syndrome (SRS) with typical features and growth retardation, but no gene has been conclusively implicated in SRS. In order to identify novel DMRs and putative imprinted genes on chromosome 7, we analyzed eight matUPD7 patients, a segmental matUPD7q31-qter, a rare patUPD7 case and ten controls on the Infinium HumanMethylation450K BeadChip with 30 017 CpG methylation probes for chromosome 7. Genome-scale analysis showed highly significant clustering of DMRs only on chromosome 7, including the known imprinted loci GRB10, SGCE/PEG10, and PEG/MEST. We found ten novel DMRs on chromosome 7, two DMRs for the predicted imprinted genes HOXA4 and GLI3 and one for the disputed imprinted gene PON1. Quantitative RT-PCR on blood RNA samples comparing matUPD7, patUPD7, and controls showed differential expression for three genes with novel DMRs, HOXA4, GLI3, and SVOPL. Allele specific expression analysis confirmed maternal only expression of SVOPL and imprinting of HOXA4 was supported by monoallelic expression. These results present the first comprehensive map of parent-of-origin specific DMRs on human chromosome 7, suggesting many new imprinted sites.

  17. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteracaea)

    NARCIS (Netherlands)

    Vijverberg, K.; Hulst, van der R.G.M.; Lindhout, W.H.; Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  18. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae)

    NARCIS (Netherlands)

    Vijverberg, Kitty; van der Hulst, R.G.M.; Lindhout, P.; Van Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  19. Fine Mapping and Evolution of a QTL Region on Cattle Chromosome 3

    Science.gov (United States)

    Donthu, Ravikiran

    2009-01-01

    The goal of my dissertation was to fine map the milk yield and composition quantitative trait loci (QTL) mapped to cattle chromosome 3 (BTA3) by Heyen et al. (1999) and to identify candidate genes affecting these traits. To accomplish this, the region between "BL41" and "TGLA263" was mapped to the cattle genome sequence assembly Btau 3.1 and a…

  20. Allelic gains and losses in distinct regions of chromosome 6 in gastric carcinoma

    NARCIS (Netherlands)

    Carvalho, B; van der Veen, AY; Gartner, F; Carneiro, F; Seruca, R; Buys, CHCM; Kok, K

    2001-01-01

    In gastric cancer, alterations in the long arm of chromosome 6 are a frequent event. Two regions of heterozygous loss have been described: 6q16.3 similar to 6q23 and 6q26 similar to 6q27. We have evaluated by microsatellite and FISH analyses the 6q status of three cell lines that we established from

  1. Copy number variations of chromosome 16p13.1 region associated with schizophrenia

    NARCIS (Netherlands)

    Ingason, A.; Rujescu, D.; Cichon, S.; Sigurdsson, E.; Sigmundsson, T.; Pietilainen, O.P.H.; Buizer-Voskamp, J.E.; Strengman, E.; Francks, C.; Muglia, P.; Gylfason, A.; Gustafsson, O.; Olason, P.I.; Steinberg, S.; Hansen, T.; Jakobsen, K.D.; Rasmussen, H.B.; Giegling, I.; Moller, H.J.; Hartmann, A.; Crombie, C.; Fraser, G.; Walker, N.; Lonnqvist, J.; Suvisaari, J.; Tuulio-Henriksson, A.; Bramon, E.; Kiemeney, L.A.L.M.; Franke, B.; Murray, R.; Vassos, E.; Toulopoulou, T.; Muhleisen, T.W.; Tosato, S.; Ruggeri, M.; Djurovic, S.; Andreassen, O.A.; Zhang, Z.; Werge, T.; Ophoff, R.A.; Rietschel, M.; Nothen, M.M.; Petursson, H.; Stefansson, H.; Peltonen, L.; Collier, D.; Stefansson, K.; St Clair, D.M.

    2011-01-01

    Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 3

  2. Gene recovery microdissection (GRM) a process for producing chromosome region-specific libraries of expressed genes

    Energy Technology Data Exchange (ETDEWEB)

    Christian, A T; Coleman, M A; Tucker, J D

    2001-02-08

    Gene Recovery Microdissection (GRM) is a unique and cost-effective process for producing chromosome region-specific libraries of expressed genes. It accelerates the pace, reduces the cost, and extends the capabilities of functional genomic research, the means by which scientists will put to life-saving, life-enhancing use their knowledge of any plant or animal genome.

  3. Identification of a short region on chromosome 6 affecting direct calving ease in Piedmontese cattle breed.

    Directory of Open Access Journals (Sweden)

    Silvia Bongiorni

    Full Text Available Calving in cattle is affected by calf morphology and by dam characteristics. It is described by two different traits: maternal calving ease, which is the ability to generate dams with good physiological predisposition to calving, and direct calving ease, which is the ability to generate calves that are easily born. The aim of this study was to identify regions of cattle genome harboring genes possibly affecting direct calving ease in the Piedmontese cattle breed. A population of 323 bulls scored for direct calving ease (EBV was analyzed by a medium-density SNP marker panel (54,001 SNPs to perform a genome-wide scan. The strongest signal was detected on chromosome 6 between 37.8 and 38.7 Mb where 13 SNPs associated to direct calving ease were found. Three genes are located in this region: LAP3, encoding for a leucine aminopeptidase involved in the oxytocin hydrolysis; NCAPG, encoding for a non-SMC condensin I complex, which has been associated in cattle with fetal growth and carcass size; and LCORL, which has been associated to height in humans and cattle. To further confirm the results of the genome-wide scan we genotyped additional SNPs within these genes and analyzed their association with direct calving ease. The results of this additional analysis fully confirmed the findings of the GWAS and particularly indicated LAP3 as the most probable gene involved. Linkage Disequilibrium (LD analysis showed high correlation between SNPs located within LAP3 and LCORL indicating a possible selection signature due either to increased fitness or breeders' selection for the trait.

  4. A physical map of the chromosomal region determining O-antigen biosynthesis in Vibrio cholerae O1.

    Science.gov (United States)

    Ward, H M; Morelli, G; Kamke, M; Morona, R; Yeadon, J; Hackett, J A; Manning, P A

    1987-01-01

    We have previously described the cosmid cloning of the genes determining the biosynthesis of the Inaba and Ogawa O-antigens of the lipopolysaccharides of Vibrio cholerae O1 (Manning et al., 1986). By Southern hybridization analysis of chromosomal and cosmid DNA, and heteroduplex analysis between the clones we have been able to precisely define the region of contiguous chromosomal DNA in the vicinity of the O-antigen-encoding region. These data and comparison of end points of clones and of deletion derivatives demonstrate that at least 16 kb of a 19-kb SstI fragment is required to encode O-antigen biosynthesis. Expression of O-antigen is independent of the orientation of this SstI fragment with respect to cloning vectors suggesting that its regulatory region has been cloned intact. No detectable differences were observed in the restriction patterns of the Inaba and Ogawa coding regions implying that only minor changes are involved when serotype conversion (Inaba to Ogawa or vice versa) occurs. Bhaskaran [Ind. J. Med. Res. 47 (1959) 253-260] originally defined this region associated with O-antigen biosynthesis oag; however, to be consistent with other organisms [Hitchcock et al., J. Bacteriol. 166 (1986) 699-705], it is suggested this be changed to rfb.

  5. A complex chromosome rearrangement involving four chromosomes, nine breakpoints and a cryptic 0.6-Mb deletion in a boy with cerebellar hypoplasia and defects in skull ossification.

    Science.gov (United States)

    Guilherme, R S; Cernach, M C S P; Sfakianakis, T E; Takeno, S S; Nardozza, L M M; Rossi, C; Bhatt, S S; Liehr, T; Melaragno, M I

    2013-01-01

    Constitutional complex chromosomal rearrangements (CCRs) are considered rare cytogenetic events. Most apparently balanced CCRs are de novo and are usually found in patients with abnormal phenotypes. High-resolution techniques are unveiling genomic imbalances in a great percentage of these cases. In this paper, we report a patient with growth and developmental delay, dysmorphic features, nervous system anomalies (pachygyria, hypoplasia of the corpus callosum and cerebellum), a marked reduction in the ossification of the cranial vault, skull base sclerosis, and cardiopathy who presents a CCR with 9 breakpoints involving 4 chromosomes (3, 6, 8 and 14) and a 0.6-Mb deletion in 14q24.1. Although the only genomic imbalance revealed by the array technique was a deletion, the clinical phenotype of the patient most likely cannot be attributed exclusively to haploinsufficiency. Other events must also be considered, including the disruption of critical genes and position effects. A combination of several different investigative approaches (G-banding, FISH with different probes and SNP array techniques) was required to describe this CCR in full, suggesting that CCRs may be more frequent than initially thought. Additionally, we propose that a chain chromosome breakage mechanism may have occurred as a single rearrangement event resulting in this CCR. This study demonstrates the importance of applying different cytogenetic and molecular techniques to detect subtle rearrangements and to delineate the rearrangements at a more accurate level, providing a better understanding of the mechanisms involved in CCR formation and a better correlation with phenotype.

  6. Control of bacterial chromosome replication by non-coding regions outside the origin

    DEFF Research Database (Denmark)

    Frimodt-Møller, Jakob; Charbon, Godefroid; Løbner-Olesen, Anders

    2016-01-01

    Chromosome replication in Eubacteria is initiated by initiator protein(s) binding to specific sites within the replication origin, oriC. Recently, initiator protein binding to chromosomal regions outside the origin has attracted renewed attention; as such binding sites contribute to control...... the frequency of initiations. These outside-oriC binding sites function in several different ways: by steric hindrances of replication fork assembly, by titration of initiator proteins away from the origin, by performing a chaperone-like activity for inactivation- or activation of initiator proteins...

  7. The orphan nuclear receptor ROR{alpha} (RORA) maps to a conserved region of homology on human chromosome 15q21-q22 and mouse chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Giguere, V. [McGill Univ., Montreal (Canada); Beatty, B.; Squire, J. [Hospital for Sick Children, Toronto (Canada)] [and others

    1995-08-10

    ROR{alpha} is a novel member of the steroid/thyroid/retinoid receptor superfamily with unique DNA-binding properties. We have mapped the RORA gene by fluorescence in situ hybridization to human chromosome 15q21-q22. To map the mouse Rora gene, a partial mouse cDNA clone was isolated from brain. Using interspecific backcross analysis, we have mapped the Rora gene to mouse chromosome 9. This places the human RORA gene in the proximity of the PML gene, which is involved in a reciprocal chromosomal translocation t(15:17) with the RARA gene in patients with acute promyelocytic leukemia. 13 refs., 2 figs.

  8. Evolution of the DAZ gene and the AZFc region on primate Y chromosomes

    Directory of Open Access Journals (Sweden)

    Yu Jane-Fang

    2008-03-01

    Full Text Available Abstract Background The Azoospermia Factor c (AZFc region of the human Y chromosome is a unique product of segmental duplication. It consists almost entirely of very long amplicons, represented by different colors, and is frequently deleted in subfertile men. Most of the AZFc amplicons have high sequence similarity with autosomal segments, indicating recent duplication and transposition to the Y chromosome. The Deleted in Azoospermia (DAZ gene within the red-amplicon arose from an ancestral autosomal DAZ-like (DAZL gene. It varies significantly between different men regarding to its copy number and the numbers of RNA recognition motif and DAZ repeat it encodes. We used Southern analyses to study the evolution of DAZ and AZFc amplicons on the Y chromosomes of primates. Results The Old World monkey rhesus macaque has only one DAZ gene. In contrast, the great apes have multiple copies of DAZ, ranging from 2 copies in bonobos and gorillas to at least 6 copies in orangutans, and these DAZ genes have polymorphic structures similar to those of their human counterparts. Sequences homologous to the various AZFc amplicons are present on the Y chromosomes of some but not all primates, indicating that they arrived on the Y chromosome at different times during primate evolution. Conclusion The duplication and transposition of AZFc amplicons to the human Y chromosome occurred in three waves, i.e., after the branching of the New World monkey, the gorilla, and the chimpanzee/bonobo lineages, respectively. The red-amplicon, one of the first to arrive on the Y chromosome, amplified by inverted duplication followed by direct duplication after the separation of the Old World monkey and the great ape lineages. Subsequent duplication/deletion in the various lineages gave rise to a spectrum of DAZ gene structure and copy number found in today's great apes.

  9. Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis.

    Science.gov (United States)

    Nakano, Hiroshi; Funasaka, Tatsuyoshi; Hashizume, Chieko; Wong, Richard W

    2010-04-01

    Gain or loss of whole chromosomes is often observed in cancer cells and is thought to be due to aberrant chromosome segregation during mitosis. Proper chromosome segregation depends on a faithful interaction between spindle microtubules and kinetochores. Several components of the nuclear pore complex/nucleoporins play critical roles in orchestrating the rapid remodeling events that occur during mitosis. Our recent studies revealed that the nucleoporin, Rae1, plays critical roles in maintaining spindle bipolarity. Here, we show association of another nucleoporin, termed Tpr (translocated promoter region), with the molecular motors dynein and dynactin, which both orchestrate with the spindle checkpoints Mad1 and Mad2 during cell division. Overexpression of Tpr enhanced multinucleated cell formation. RNA interference-mediated knockdown of Tpr caused a severe lagging chromosome phenotype and disrupted spindle checkpoint proteins expression and localization. Next, we performed a series of rescue and dominant negative experiments to confirm that Tpr orchestrates proper chromosome segregation through interaction with dynein light chain. Our data indicate that Tpr functions as a spatial and temporal regulator of spindle checkpoints, ensuring the efficient recruitment of checkpoint proteins to the molecular motor dynein to promote proper anaphase formation.

  10. Systematic Triple-Mutant Analysis Uncovers Functional Connectivity between Pathways Involved in Chromosome Regulation

    Directory of Open Access Journals (Sweden)

    James E. Haber

    2013-06-01

    Full Text Available Genetic interactions reveal the functional relationships between pairs of genes. In this study, we describe a method for the systematic generation and quantitation of triple mutants, termed triple-mutant analysis (TMA. We have used this approach to interrogate partially redundant pairs of genes in S. cerevisiae, including ASF1 and CAC1, two histone chaperones. After subjecting asf1Δ cac1Δ to TMA, we found that the Swi/Snf Rdh54 protein compensates for the absence of Asf1 and Cac1. Rdh54 more strongly associates with the chromatin apparatus and the pericentromeric region in the double mutant. Moreover, Asf1 is responsible for the synthetic lethality observed in cac1Δ strains lacking the HIRA-like proteins. A similar TMA was carried out after deleting both CLB5 and CLB6, cyclins that regulate DNA replication, revealing a strong functional connection to chromosome segregation. This approach can reveal functional redundancies that cannot be uncovered through traditional double-mutant analyses.

  11. Characterization of the OmyY1 Region on the Rainbow Trout Y Chromosome

    Directory of Open Access Journals (Sweden)

    Ruth B. Phillips

    2013-01-01

    Full Text Available We characterized the male-specific region on the Y chromosome of rainbow trout, which contains both sdY (the sex-determining gene and the male-specific genetic marker, OmyY1. Several clones containing the OmyY1 marker were screened from a BAC library from a YY clonal line and found to be part of an 800 kb BAC contig. Using fluorescence in situ hybridization (FISH, these clones were localized to the end of the short arm of the Y chromosome in rainbow trout, with an additional signal on the end of the X chromosome in many cells. We sequenced a minimum tiling path of these clones using Illumina and 454 pyrosequencing. The region is rich in transposons and rDNA, but also appears to contain several single-copy protein-coding genes. Most of these genes are also found on the X chromosome; and in several cases sex-specific SNPs in these genes were identified between the male (YY and female (XX homozygous clonal lines. Additional genes were identified by hybridization of the BACs to the cGRASP salmonid 4x44K oligo microarray. By BLASTn evaluations using hypothetical transcripts of OmyY1-linked candidate genes as query against several EST databases, we conclude at least 12 of these candidate genes are likely functional, and expressed.

  12. Characterization of the OmyY1 region on the rainbow trout Y chromosome

    Science.gov (United States)

    Phillips, Ruth B.; DeKoning, Jenefer J.; Brunelli, Joseph P.; Faber-Hammond, Joshua J.; Hansen, John D.; Christensen, Kris A.; Renn, Suzy C.P.; Thorgaard, Gary H.

    2013-01-01

    We characterized the male-specific region on the Y chromosome of rainbow trout, which contains both sdY (the sex-determining gene) and the male-specific genetic marker, OmyY1. Several clones containing the OmyY1 marker were screened from a BAC library from a YY clonal line and found to be part of an 800 kb BAC contig. Using fluorescence in situ hybridization (FISH), these clones were localized to the end of the short arm of the Y chromosome in rainbow trout, with an additional signal on the end of the X chromosome in many cells. We sequenced a minimum tiling path of these clones using Illumina and 454 pyrosequencing. The region is rich in transposons and rDNA, but also appears to contain several single-copy protein-coding genes. Most of these genes are also found on the X chromosome; and in several cases sex-specific SNPs in these genes were identified between the male (YY) and female (XX) homozygous clonal lines. Additional genes were identified by hybridization of the BACs to the cGRASP salmonid 4x44K oligo microarray. By BLASTn evaluations using hypothetical transcripts of OmyY1-linked candidate genes as query against several EST databases, we conclude at least 12 of these candidate genes are likely functional, and expressed.

  13. Sequence signatures involved in targeting the male-specific lethal complex to X-chromosomal genes in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Philip Philge

    2012-03-01

    Full Text Available Abstract Background In Drosophila melanogaster, the dosage-compensation system that equalizes X-linked gene expression between males and females, thereby assuring that an appropriate balance is maintained between the expression of genes on the X chromosome(s and the autosomes, is at least partially mediated by the Male-Specific Lethal (MSL complex. This complex binds to genes with a preference for exons on the male X chromosome with a 3' bias, and it targets most expressed genes on the X chromosome. However, a number of genes are expressed but not targeted by the complex. High affinity sites seem to be responsible for initial recruitment of the complex to the X chromosome, but the targeting to and within individual genes is poorly understood. Results We have extensively examined X chromosome sequence variation within five types of gene features (promoters, 5' UTRs, coding sequences, introns, 3' UTRs and intergenic sequences, and assessed its potential involvement in dosage compensation. Presented results show that: the X chromosome has a distinct sequence composition within its gene features; some of the detected variation correlates with genes targeted by the MSL-complex; the insulator protein BEAF-32 preferentially binds upstream of MSL-bound genes; BEAF-32 and MOF co-localizes in promoters; and that bound genes have a distinct sequence composition that shows a 3' bias within coding sequence. Conclusions Although, many strongly bound genes are close to a high affinity site neither our promoter motif nor our coding sequence signatures show any correlation to HAS. Based on the results presented here, we believe that there are sequences in the promoters and coding sequences of targeted genes that have the potential to direct the secondary spreading of the MSL-complex to nearby genes.

  14. The Involvement of Rural Entrepreneurship In The Regional Development

    Directory of Open Access Journals (Sweden)

    Marin Burcea

    2014-12-01

    Full Text Available The aims of the present paper are to emphasize the importance of the rural entrepreneurship involvement in the regional development and to analyse the results of a research regarding the cooperation between the stakeholders of the local and regional development. A set of two hypotheses has been tested by using the data of a sociological survey focused on entrepreneurship and on the potential entrepreneurs from the rural area, belonging to five development regions. The results of our research highlight that the relationships between the rural area business environment and the other actors involved in the regional development (local public authorities, professional associations, institutions centred on regional development are influenced by the framework of organisation and cooperation with the local business environment.

  15. Nucleolar organizer regions in Sittasomus griseicapillus and Lepidocolaptes angustirostris (Aves, Dendrocolaptidae: evidence of a chromosome inversion

    Directory of Open Access Journals (Sweden)

    Marcelo de Oliveira Barbosa

    2013-01-01

    Full Text Available Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs. Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group.

  16. Computational Comparison of Human Genomic Sequence Assemblies for a Region of Chromosome 4

    OpenAIRE

    Semple, Colin; Stewart W. Morris; Porteous, David J.; Evans, Kathryn L.

    2002-01-01

    Much of the available human genomic sequence data exist in a fragmentary draft state following the completion of the initial high-volume sequencing performed by the International Human Genome Sequencing Consortium (IHGSC) and Celera Genomics (CG). We compared six draft genome assemblies over a region of chromosome 4p (D4S394–D4S403), two consecutive releases by the IHGSC at University of California, Santa Cruz (UCSC), two consecutive releases from the National Centre for Biotechnology Informa...

  17. Physical mapping and YAC contig analysis of the region surrounding Xist on the mouse X chromosome.

    Science.gov (United States)

    Heard, E; Simmler, M C; Larin, Z; Rougeulle, C; Courtier, B; Lehrach, H; Avner, P

    1993-03-01

    The Xist sequence has been proposed as a potential candidate for the X-inactivation center based both on its localization within the candidate region for the X-inactivation center in man and mouse and on its unique pattern of expression from the inactive X chromosome. We have cloned 550 kb of DNA surrounding the mouse Xist sequence in contiguously overlapping YAC clones and have developed a long-range restriction map that spans almost 1 Mb of this region and includes this YAC contig. The detailed restriction map we have established provides a framework for the identification of expressed sequences other than Xist that may equally exhibit unusual expression characteristics associated with X inactivation. The presence of possible structural or methylation differences within this region between the active and inactive X chromosomes has been investigated through comparative analysis of male and female genomic DNA, and we report here the identification of certain CpG-containing restriction sites around Xist that have an interesting differential methylation status on the inactive and active X chromosomes.

  18. A new function of microtubule-associated protein tau: involvement in chromosome stability.

    Science.gov (United States)

    Rossi, Giacomina; Dalprà, Leda; Crosti, Francesca; Lissoni, Sara; Sciacca, Francesca L; Catania, Marcella; Di Fede, Giuseppe; Mangieri, Michela; Giaccone, Giorgio; Croci, Danilo; Tagliavini, Fabrizio

    2008-06-15

    Tau is a microtubule-associated protein that promotes assembly and stabilization of cytoskeleton microtubules. It is mostly expressed in neuronal and glial cells but it is also present in non-neural cells such as fibroblasts and lymphocytes. An altered tau produces cytoskeleton pathology resulting in neurodegenerative diseases such as Alzheimer's disease and tauopathies. Tau has been suggested to be a multifunctional protein, due to its localization in different cellular compartments. However its further functions are still unclear. We analyzed the distribution of tau in human skin fibroblasts showing its localization in the nucleus and along mitotic chromosomes. Then, we investigated if an altered tau, such as the P301L mutated protein associated with frontotemporal dementia, could produce nuclear pathology. We found that patients carrying the mutation consistently had several chromosome aberrations in their fibroblasts and lymphocytes: chromosome and chromatid breakages or gaps, aneuploidies, translocations, in addition to chromatin bridges and decondensed chromosomes. Our findings argue for a role of tau in chromosome stability by means of its interaction with both microtubules and chromatin.

  19. Correlation between missed abortion and insertional translocation involving chromosomes 1 and 7

    Directory of Open Access Journals (Sweden)

    Ahmed Husseiny

    2012-01-01

    Full Text Available Background: Missed abortion (Silent miscarriage is defined as intrauterine fetal death before twenty weeks gestation. One of the most common causes of early missed abortions (before 10 weeks gestation is cytogenetic abnormalities. Objective: To asses if there is a correlation between chromosomal aberrations (especially in chromosome 7 and missed abortion among at least two generations.Materials and Methods: After exclusion of direct causes of missed abortion, this study included 60 women (the study group who had first trimestric missed abortion and 30 healthy women who did not suffer from any diseases during their pregnancy and had apparently normal outcome (the control group. All cases were diagnosed; the blood and tissue samples were collected from the mothers and abortuses from the Department of Obstetrics and Gynecology, Maternity Hospital, Ain Shams University. Cytogenetic analyses were performed by using conventional technique and G/T banding techniques and Fluorescence In Situ Hybridization (FISH analysis with a whole chromosome 7 painting probe (WCP7 and a 7q subterminal probe (7q36, qter, prepared by chromosome micro dissection technique was used for confirming the specific chromosomal abnormality.

  20. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

    2012-02-01

    The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

  1. Conserved gene arrangement in the origin region of the Streptomyces coelicolor chromosome.

    OpenAIRE

    1992-01-01

    A 23-kb fragment of the Streptomyces coelicolor chromosome spanning the dnaA region has been isolated as a cosmid clone. Nucleotide sequence analysis of a 5-kb portion shows that the genes for the RNase P protein (rnpA), ribosomal protein L34 (rpmH), the replication initiator protein (dnaA), and the beta subunit of DNA polymerase III (dnaN) are present in the highly conserved gene arrangement found in all eubacterial genomes studied so far. The dnaA-dnaN intergenic region is approximately 1 k...

  2. Identification and uniparental expression of a novel gene from the Prader-Willi region of chromosome 15

    Energy Technology Data Exchange (ETDEWEB)

    Wevrick, R.; Kerns, J.A.; Francke, U. [Stanford Univ., CA (United States)

    1994-09-01

    The Prader-Willi syndrome (PWS) is a neurobehavioral disorder which occurs at a frequency of about 1/25,000. Most patients ({approximately}70%) have a cytogentic deletion of their paternal 15q11-q13 region, while {approximately}30% have uniparental maternal disomy. The parent of origin dependence of the phenotype is thought to be reflective of the uniparental pattern of expression of genes in the region, a phenomenon known as genomic imprinting. A small subset of PWS patient with a typical cytogenetic rearrangements has defined a critical region for genes involved in PWS. We have used STSs from the region to construct a YAC contig including the entire PWS critical region, which is about 350 kb considering presently characterized deletions. We are now using these YACs to isolate and characterize novel genes potentially involved in PWS. Overlapping YACs from the critical region were subjected to the technique of cDNA selection. Gel-purified YAC DNA was biotinylated during PCR amplification and annealed in solution to amplified cDNA. cDNAs remaining after hybridization washing, and denaturation of the hybrids were tested for localization within the YAC contig. One such cDNA mapped back to the YAC contig and was further analyzed. A full length cDNA clone was isolated from a fetal brain library and sequenced. The pattern of expression was determined in cell lines derived from Prader-Willi and Angelman patients and in normal individuals. The gene was found to have monoallelic, paternal expression in normal individuals and is marginally or not expressed in cell lines derived form Prader-Willi individuals. Expression in cell lines from Angelman patients, who are deleted for the same region on the maternal chromosome 15, was normal. Thus this apparently maternally imprinted gene is a candidate for involvement in the Prader-Willi phenotype.

  3. Cytokinesis breaks dicentric chromosomes preferentially at pericentromeric regions and telomere fusions.

    Science.gov (United States)

    Lopez, Virginia; Barinova, Natalja; Onishi, Masayuki; Pobiega, Sabrina; Pringle, John R; Dubrana, Karine; Marcand, Stéphane

    2015-02-01

    Dicentric chromosomes are unstable products of erroneous DNA repair events that can lead to further genome rearrangements and extended gene copy number variations. During mitosis, they form anaphase bridges, resulting in chromosome breakage by an unknown mechanism. In budding yeast, dicentrics generated by telomere fusion break at the fusion, a process that restores the parental karyotype and protects cells from rare accidental telomere fusion. Here, we observed that dicentrics lacking telomere fusion preferentially break within a 25- to 30-kb-long region next to the centromeres. In all cases, dicentric breakage requires anaphase exit, ruling out stretching by the elongated mitotic spindle as the cause of breakage. Instead, breakage requires cytokinesis. In the presence of dicentrics, the cytokinetic septa pinch the nucleus, suggesting that dicentrics are severed after actomyosin ring contraction. At this time, centromeres and spindle pole bodies relocate to the bud neck, explaining how cytokinesis can sever dicentrics near centromeres.

  4. Patterns of association in the human metaphase complement: ring analysis and estimation of associativity of specific chromosome regions.

    Science.gov (United States)

    Rodman, T C; Flehinger, B J; Squire, R D

    1978-02-23

    The pattern of metaphase chromosome association in the human complement was studied by two methods of statistical analysis of interchromosomal distances. Those methods included ring analysis in which a characteristic position of the centromere of each chromosome relative to the center of a two dimensional representation of a metaphase complement was defined, and estimation of the capacity for associativity of each of three regions of each chromosome: the centromere (c) and the ends of each arm (p, q). The following information was obtained: 1. In general, the distance from the center is directly related to chromosome size. 2. The most notable deviation from that size-related progression is displayed by the X chromosomes. The markedly peripheral position of the X is characteristic of both X's of the female and the single X of the male. 3. The relative associativity of each chromosome of the complement is, in general, inversely related to size with an additional preferential capacity of associativity displayed by the acrocentric chromosomes. Analyses of the different inter-regional classes established that the supplementary associativity factor of the acrocentric chromosomes was inherent in their pericentromeric and p-arm regions and excluded the ends of the q arms from participation in that factor. 4. Those analyses demonstrated that the specific morphology or 'geometry' of the acrocentric chromosomes contributes little to their high relative associativity. In addition to the tendency for the c/p regions of the acrocentric chromosomes to associate with each other, presumably because of their common function in nucleolar organization, those regions also displayed a propensity to associate with the distal regions of the arms of other chromosomes. A molecular basis for that propensity other than that of ribosomal DNA is postulated to be that of other fractions of highly reiterated DNA sequences. 5. Analysis of the relative associativities of each of the three regions

  5. Evidence of a locus for orofacial clefting on human chromosome 6p24 and STS content map of the region.

    Science.gov (United States)

    Davies, A F; Stephens, R J; Olavesen, M G; Heather, L; Dixon, M J; Magee, A; Flinter, F; Ragoussis, J

    1995-01-01

    Orofacial clefting is genetically complex, no single gene being responsible for all forms. It can, however, result from a single gene defect either as part of a syndrome (e.g. van der Woude syndrome, Treacher-Collins syndrome, velo-cardio-facial syndrome) or as an isolated phenotypic effect (e.g. X-linked cleft palate; non-syndromic, autosomal dominant orofacial clefting). Several studies have suggested that chromosome 6p is a candidate region for a locus involved in orofacial clefting. We have used YAC clones from contigs in 6p25-p23 to investigate three unrelated cases of cleft lip and palate coincident with chromosome 6p abnormalities. Case 1 has bilateral cleft lip and palate and a balanced translocation reported as 46,XY,t(6,7)(p23;q36.1). Case 2 has multiple abnormalities including cleft lip and palate and was reported as 46,XX,del(6)(p23;pter). Case 3 has bilateral cleft lip and palate and carries a balanced translocation reported as 46,XX,t(6;9)(p23;q22.3). We have identified two YAC clones, both of which cross the breakpoint in cases 1 and 3 and are deleted in case 2. These clones map to 6p24.3 and therefore suggest the presence of a locus for orofacial clefting in this region. The HGP22 and AP2 genes, potentially involved in face formation, have been found to flank this region, while F13A maps further telomeric in 6p24.3/25.

  6. Dynamics of rye chromosome 1R regions with high or low crossover frequency in homology search and synapsis development.

    Directory of Open Access Journals (Sweden)

    Nohelia T Valenzuela

    Full Text Available In many organisms, homologous pairing and synapsis depend on the meiotic recombination machinery that repairs double-strand DNA breaks (DSBs produced at the onset of meiosis. The culmination of recombination via crossover gives rise to chiasmata, which locate distally in many plant species such as rye, Secale cereale. Although, synapsis initiates close to the chromosome ends, a direct effect of regions with high crossover frequency on partner identification and synapsis initiation has not been demonstrated. Here, we analyze the dynamics of distal and proximal regions of a rye chromosome introgressed into wheat to define their role on meiotic homology search and synapsis. We have used lines with a pair of two-armed chromosome 1R of rye, or a pair of telocentrics of its long arm (1RL, which were homozygous for the standard 1RL structure, homozygous for an inversion of 1RL that changes chiasma location from distal to proximal, or heterozygous for the inversion. Physical mapping of recombination produced in the ditelocentric heterozygote (1RL/1RL(inv showed that 70% of crossovers in the arm were confined to a terminal segment representing 10% of the 1RL length. The dynamics of the arms 1RL and 1RL(inv during zygotene demonstrates that crossover-rich regions are more active in recognizing the homologous partner and developing synapsis than crossover-poor regions. When the crossover-rich regions are positioned in the vicinity of chromosome ends, their association is facilitated by telomere clustering; when they are positioned centrally in one of the two-armed chromosomes and distally in the homolog, their association is probably derived from chromosome elongation. On the other hand, chromosome movements that disassemble the bouquet may facilitate chromosome pairing correction by dissolution of improper chromosome associations. Taken together, these data support that repair of DSBs via crossover is essential in both the search of the homologous partner

  7. A defined terminal region of the E. coli chromosome shows late segregation and high FtsK activity.

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    Marie Deghorain

    Full Text Available BACKGROUND: The FtsK DNA-translocase controls the last steps of chromosome segregation in E. coli. It translocates sister chromosomes using the KOPS DNA motifs to orient its activity, and controls the resolution of dimeric forms of sister chromosomes by XerCD-mediated recombination at the dif site and their decatenation by TopoIV. METHODOLOGY: We have used XerCD/dif recombination as a genetic trap to probe the interaction of FtsK with loci located in different regions of the chromosome. This assay revealed that the activity of FtsK is restricted to a ∼400 kb terminal region of the chromosome around the natural position of the dif site. Preferential interaction with this region required the tethering of FtsK to the division septum via its N-terminal domain as well as its translocation activity. However, the KOPS-recognition activity of FtsK was not required. Displacement of replication termination outside the FtsK high activity region had no effect on FtsK activity and deletion of a part of this region was not compensated by its extension to neighbouring regions. By observing the fate of fluorescent-tagged loci of the ter region, we found that segregation of the FtsK high activity region is delayed compared to that of its adjacent regions. SIGNIFICANCE: Our results show that a restricted terminal region of the chromosome is specifically dedicated to the last steps of chromosome segregation and to their coupling with cell division by FtsK.

  8. A distinct type of heterochromatin at the telomeric region of the Drosophila melanogaster Y chromosome.

    Directory of Open Access Journals (Sweden)

    Sidney H Wang

    Full Text Available Heterochromatin assembly and its associated phenotype, position effect variegation (PEV, provide an informative system to study chromatin structure and genome packaging. In the fruit fly Drosophila melanogaster, the Y chromosome is entirely heterochromatic in all cell types except the male germline; as such, Y chromosome dosage is a potent modifier of PEV. However, neither Y heterochromatin composition, nor its assembly, has been carefully studied. Here, we report the mapping and characterization of eight reporter lines that show male-specific PEV. In all eight cases, the reporter insertion sites lie in the telomeric transposon array (HeT-A and TART-B2 homologous repeats of the Y chromosome short arm (Ys. Investigations of the impact on the PEV phenotype of mutations in known heterochromatin proteins (i.e., modifiers of PEV show that this Ys telomeric region is a unique heterochromatin domain: it displays sensitivity to mutations in HP1a, EGG and SU(VAR3-9, but no sensitivity to Su(z2 mutations. It appears that the endo-siRNA pathway plays a major targeting role for this domain. Interestingly, an ectopic copy of 1360 is sufficient to induce a piRNA targeting mechanism to further enhance silencing of a reporter cytologically localized to the Ys telomere. These results demonstrate the diversity of heterochromatin domains, and the corresponding variation in potential targeting mechanisms.

  9. Nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias

    Energy Technology Data Exchange (ETDEWEB)

    Huebner, K.; Isobe, M.; Chao, M.; Bothwell, M.; Ross, A.H.; Finan, J.; Hoxie, J.A.; Sehgal, A.; Buck, C.R.; Lanahan, A.

    1986-03-01

    Genomic and cDNA clones for the human nerve growth factor receptor have been used in conjunction with somatic cell hybrid analysis and in situ hybridization to localize the nerve growth factor receptor locus to human chromosome region 17q12-q22. Additionally, part, if not all, of the nerve growth factor receptor locus is present on the translocated portion of 17q (17q21-qter) from a poorly differential acute leukemia in which the chromosome 17 breakpoint was indistinguishable cytogenetically from the 17 breakpoint observed in the t(15;17)(q22;q21) translocation associated with acute promyelocytic leukemia. Thus the nerve growth factor receptor locus may be closely distal to the acute promyelocytic leukemia-associated chromosome 17 breakpoint at 17q21.

  10. Molecular dissection of a contiguous gene syndrome: Frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated island in the Miller-Dieker chromosome region

    Energy Technology Data Exchange (ETDEWEB)

    Ledbetter, D.H.; Ledbetter, S.A.; vanTuinen, P.; Summers, K.M.; Robinson, T.J.; Nakamura, Yusuke; Wolff, R.; White, R.; Barker, D.F.; Wallace, M.R.; Collins, F.S.; Dobyns, W.B. (Baylor College of Medicine, Houston, TX (USA))

    1989-07-01

    The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be <15 kb apart. Three overlapping cosmids spanning >100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region.

  11. The distal end of porcine chromosome 6p is involved in the regulation of skatole levels in boars

    Directory of Open Access Journals (Sweden)

    Crooijmans Richard PMA

    2011-04-01

    Full Text Available Abstract Background Boar taint is an unpleasant condition of pork, mainly due to the accumulation of androstenone and skatole in male pigs at onset of puberty. This condition is the cause of considerable economic losses in the pig industry and the most common practice to control it is to castrate male piglets. Because of the economic and animal welfare concerns there is interest in developing genetic markers that could be used in selection schemes to decrease the incidence of boar taint. The Porcine 60 K SNP Beadchip was used to genotype 891 pigs from a composite Duroc sire line, for which skatole levels in fat had been collected. Results The genome-wide association study revealed that 16 SNPs (single nucleotide polymorphisms located on the proximal region of chromosome 6 were significantly associated with skatole levels. These SNPs are grouped in three separate clusters located in the initial 6 Mb region of chromosome 6. The differences observed between the homozygote genotypes for SNPs in the three clusters were substantial, including a difference of 102.8 ng/g skatole in melted fat between the homozygotes for the ALGA0107039 marker. Single SNPs explain up to 22% of the phenotypic variance. No obvious candidate genes could be pinpointed in the region, which may be due to the need of further annotation of the pig genome. Conclusions This study demonstrated new SNP markers significantly associated with skatole levels in the distal region of chromosome 6p. These markers defined three independent clusters in the region, which contain a low number of protein-coding genes. The considerable differences observed between the homozygous genotypes for several SNPs may be used in future selection schemes to reduce skatole levels in pigs

  12. Genome-wide association study to identify chromosomal regions associated with antibody response to Mycobacterium avium subspecies paratuberculosis in milk of Dutch Holstein-Friesians.

    Science.gov (United States)

    van Hulzen, K J E; Schopen, G C B; van Arendonk, J A M; Nielen, M; Koets, A P; Schrooten, C; Heuven, H C M

    2012-05-01

    Heritability of susceptibility to Johne's disease in cattle has been shown to vary from 0.041 to 0.159. Although the presence of genetic variation involved in susceptibility to Johne's disease has been demonstrated, the understanding of genes contributing to the genetic variance is far from complete. The objective of this study was to contribute to further understanding of genetic variation involved in susceptibility to Johne's disease by identifying associated chromosomal regions using a genome-wide association approach. Log-transformed ELISA test results of 265,290 individual Holstein-Friesian cows from 3,927 herds from the Netherlands were analyzed to obtain sire estimated breeding values for Mycobacterium avium subspecies paratuberculosis (MAP)-specific antibody response in milk using a sire-maternal grandsire model with fixed effects for parity, year of birth, lactation stage, and herd; a covariate for milk yield on test day; and random effects for sire, maternal grandsire, and error. For 192 sires with estimated breeding values with a minimum reliability of 70%, single nucleotide polymorphism (SNP) typing was conducted by a multiple SNP analysis with a random polygenic effect fitting 37,869 SNP simultaneously. Five SNP associated with MAP-specific antibody response in milk were identified distributed over 4 chromosomal regions (chromosome 4, 15, 18, and 28). Thirteen putative SNP associated with MAP-specific antibody response in milk were identified distributed over 10 chromosomes (chromosome 4, 14, 16, 18, 19, 20, 21, 26, 27, and 29). This knowledge contributes to the current understanding of genetic variation involved in Johne's disease susceptibility and facilitates control of Johne's disease and improvement of health status by breeding.

  13. LOH at chromosome 9q34.3 and the Notch1 gene methylation are less involved in oral squamous cell carcinomas

    DEFF Research Database (Denmark)

    Gao, Shan; Krogdahl, Annelise; Eiberg, Hans;

    2007-01-01

    BACKGROUND: Previous studies of oral carcinomas have shown that both loss of heterozygosity (LOH) and hypermethylation at chromosome 9q33 to 9q34.2 are frequent. The present study investigates the frequency of Notch1 gene methylation and LOH at 9q34.3 region. METHODS: Gene promoter hypermethylation...... of the Notch1 gene was analysed by methylation-specific PCR and LOH was analysed using microsatellite markers. RESULTS: We found LOH at 9q34.3 in three patients and methylation of the Notch1 gene only in two patients with oral carcinoma. CONCLUSION: Comparing with the alterations at 9q33 to 34.2 regions, LOH...... at 9q34.3 and methylation of the Notch1 gene was less involved in oral squamous cell carcinomas....

  14. Antibodies to left-handed Z-DNA bind to interband regions of Drosophila polytene chromosomes

    Science.gov (United States)

    Nordheim, Alfred; Pardue, Mary Lou; Lafer, Eileen M.; Möller, Achim; Stollar, B. David; Rich, Alexander

    1981-12-01

    Antibodies which are specific to the Z-DNA conformation have been purified and characterized on the basis of their binding to three different DNA polymers which can form this left-handed helix. These antibodies bind specifically to polytene chromosomes of Drosophila melanogaster as visualized by fluorescent staining. The staining is found in the interband regions and its intensity varies among different interbands in a reproducible manner. This is the first identification of the Z-DNA conformation in material of biological origin.

  15. Accurate Chromosome Segregation at First Meiotic Division Requires AGO4, a Protein Involved in RNA-Dependent DNA Methylation in Arabidopsis thaliana.

    Science.gov (United States)

    Oliver, Cecilia; Santos, Juan Luis; Pradillo, Mónica

    2016-10-01

    The RNA-directed DNA methylation (RdDM) pathway is important for the transcriptional repression of transposable elements and for heterochromatin formation. Small RNAs are key players in this process by regulating both DNA and histone methylation. Taking into account that methylation underlies gene silencing and that there are genes with meiosis-specific expression profiles, we have wondered whether genes involved in RdDM could play a role during this specialized cell division. To address this issue, we have characterized meiosis progression in pollen mother cells from Arabidopsis thaliana mutant plants defective for several proteins related to RdDM. The most relevant results were obtained for ago4-1 In this mutant, meiocytes display a slight reduction in chiasma frequency, alterations in chromatin conformation around centromeric regions, lagging chromosomes at anaphase I, and defects in spindle organization. These abnormalities lead to the formation of polyads instead of tetrads at the end of meiosis, and might be responsible for the fertility defects observed in this mutant. Findings reported here highlight an involvement of AGO4 during meiosis by ensuring accurate chromosome segregation at anaphase I.

  16. Genomic study of the critical region of chromosome 21 associated to Down syndrome

    Directory of Open Access Journals (Sweden)

    Julio César Montoya

    2011-03-01

    Full Text Available Introduction: Previous reports have identified a region of chromosome 21 known as Down ayndrome critical region (DSCR in which the expression of some genes would modulate the main clinical characteristics of this pathology. In this sense, there is currently limited information on the architecture of the DSCR associated.Objective: To obtain in silico a detailed vision of the chromatin structure associated with the evaluation of genomic covariables contained in public data bases.Methods: Taking as reference the information consigned in the National Center for Biotechnology Information, the Genome Browser from the University of California at Santa Cruz and from the HapMap project, a chromosome walk along 21 Mb of the distal portion of chromosome 21q arm was performed. In this distal portion, the number of single nucleotide polymorphisms (SNP, number of CpG islands, repetitive elements, recombination frequencies, and topographical state of that chromatin were recorded.Results: The frequency of CpG islands and Ref genes increased in the more distal 1.2 Mb DSCR that contrast with those localized near to the centromere. The highest level of recombination calculated for women was registered in the 21q22.12 to 22.3 bands. DSCR 6 and 9 genes showed a high percentage of methylation in CpG islands in DNA from normal and trisomic fibroblasts. The DSCR2 gene exhibited high levels of open chromatin and also methylation in some lysine residues of the histone H3 as relevant characteristics.Conclusion: The existence of a genomic environment characterized by high values of recombination frequencies and CpG methylation in DSCR 6 and 9 and also DSCR2 genes led us to postulate that in non-disjunction detected in Down syndrome, complex genomic, epigenetic and environmental relationships regulate some processes of meiosis.

  17. Genomic study of the critical region of chromosome 21 associated to Down syndrome

    Directory of Open Access Journals (Sweden)

    Julio César Montoya

    2011-04-01

    Full Text Available Introduction: Previous reports have identified a region of chromosome 21 known as Down ayndrome critical region (DSCR in which the expression of some genes would modulate the main clinical characteristics of this pathology. In this sense, there is currently limited information on the architecture of the DSCR associated. Objective: To obtain in silico a detailed vision of the chromatin structure associated with the evaluation of genomic covariables contained in public data bases. Methods: Taking as reference the information consigned in the National Center for Biotechnology Information, the Genome Browser from the University of California at Santa Cruz and from the HapMap project, a chromosome walk along 21 Mb of the distal portion of chromosome 21q arm was performed. In this distal portion, the number of single nucleotide polymorphisms (SNP, number of CpG islands, repetitive elements, recombination frequencies, and topographical state of that chromatin were recorded. Results: The frequency of CpG islands and Ref genes increased in the more distal 1.2 Mb DSCR that contrast with those localized near to the centromere. The highest level of recombination calculated for women was registered in the 21q22.12 to 22.3 bands. DSCR 6 and 9 genes showed a high percentage of methylation in CpG islands in DNA from normal and trisomic fibroblasts. The DSCR2 gene exhibited high levels of open chromatin and also methylation in some lysine residues of the histone H3 as relevant characteristics. Conclusion: The existence of a genomic environment characterized by high values of recombination frequencies and CpG methylation in DSCR 6 and 9 and also DSCR2 genes led us to postulate that in non-disjunction detected in Down syndrome, complex genomic, epigenetic and environmental relationships regulate some processes of meiosis.

  18. Major chromosomal breakpoint intervals in breast cancer tumors co-localize with differentially methylated regions.

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    Man-Hung Eric eTang

    2012-12-01

    Full Text Available Solid tumors exhibit chromosomal rearrangements resulting in gain or loss of multiple loci (copy number variation and translocations that occasionally result in the creation of novel chimeric genes. In the case of breast cancer, although most individual tumors each have unique CNV landscape the breakpoints, as measured over large datasets, appear to be non-randomly distributed in the genome. Breakpoints show a significant regional concentration at genomic loci spanning perhaps several megabases. The proximal cause of these breakpoint concentrations is a subject of speculation but is, as yet, largely unknown. To shed light on this issue, we have performed a bio-statistical analysis on our previously published data for a set of 119 breast tumors and normal controls, where each sample has both high resolution CNV and methylation data. The method examined the distribution of closeness of breakpoint regions with differentially methylated regions, coupled with additional genomic parameters, such as repeat elements and designated fragile sites in the reference genome. Through this analysis, we have identified a set of 91 regional loci called breakpoint enriched differentially methylated regions (BEDMRs characterized by altered DNA methylation in cancer compared to normal cells that are associated with frequent breakpoint concentrations within a distance of 1Mb. BEDMR loci are further associated with local hypomethylation (66% concentrations of the Alu SINE repeats within 3Mb and tend to occur near a number of cancer related genes such as the protocadherins, AKT1, DUB3, GAB2. BEDMRs seem to deregulate members of the histone gene family and chromatin remodeling factors e.g JMJD1B which might affect the chromatin structure and disrupt coordinate signaling and repair. From this analysis we propose that preference for chromosomal breakpoints is related to genome structure coupled with alterations in DNA methylation and hence chromatin structure associated

  19. Genome-wide association study identified a narrow chromosome 1 region associated with chicken growth traits.

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    Liang Xie

    Full Text Available Chicken growth traits are important economic traits in broilers. A large number of studies are available on finding genetic factors affecting chicken growth. However, most of these studies identified chromosome regions containing putative quantitative trait loci and finding causal mutations is still a challenge. In this genome-wide association study (GWAS, we identified a narrow 1.5 Mb region (173.5-175 Mb of chicken (Gallus gallus chromosome (GGA 1 to be strongly associated with chicken growth using 47,678 SNPs and 489 F2 chickens. The growth traits included aggregate body weight (BW at 0-90 d of age measured weekly, biweekly average daily gains (ADG derived from weekly body weight, and breast muscle weight (BMW, leg muscle weight (LMW and wing weight (WW at 90 d of age. Five SNPs in the 1.5 Mb KPNA3-FOXO1A region at GGA1 had the highest significant effects for all growth traits in this study, including a SNP at 8.9 Kb upstream of FOXO1A for BW at 22-48 d and 70 d, a SNP at 1.9 Kb downstream of FOXO1A for WW, a SNP at 20.9 Kb downstream of ENSGALG00000022732 for ADG at 29-42 d, a SNP in INTS6 for BW at 90 d, and a SNP in KPNA3 for BMW and LMW. The 1.5 Mb KPNA3-FOXO1A region contained two microRNA genes that could bind to messenger ribonucleic acid (mRNA of IGF1, FOXO1A and KPNA3. It was further indicated that the 1.5 Mb GGA1 region had the strongest effects on chicken growth during 22-42 d.

  20. High-resolution recombination patterns in a region of human chromosome 21 measured by sperm typing.

    Directory of Open Access Journals (Sweden)

    Irene Tiemann-Boege

    2006-05-01

    Full Text Available For decades, classical crossover studies and linkage disequilibrium (LD analysis of genomic regions suggested that human meiotic crossovers may not be randomly distributed along chromosomes but are focused instead in "hot spots." Recent sperm typing studies provided data at very high resolution and accuracy that defined the physical limits of a number of hot spots. The data were also used to test whether patterns of LD can predict hot spot locations. These sperm typing studies focused on several small regions of the genome already known or suspected of containing a hot spot based on the presence of LD breakdown or previous experimental evidence of hot spot activity. Comparable data on target regions not specifically chosen using these two criteria is lacking but is needed to make an unbiased test of whether LD data alone can accurately predict active hot spots. We used sperm typing to estimate recombination in 17 almost contiguous ~5 kb intervals spanning 103 kb of human Chromosome 21. We found two intervals that contained new hot spots. The comparison of our data with recombination rates predicted by statistical analyses of LD showed that, overall, the two datasets corresponded well, except for one predicted hot spot that showed little crossing over. This study doubles the experimental data on recombination in men at the highest resolution and accuracy and supports the emerging genome-wide picture that recombination is localized in small regions separated by cold areas. Detailed study of one of the new hot spots revealed a sperm donor with a decrease in recombination intensity at the canonical recombination site but an increase in crossover activity nearby. This unique finding suggests that the position and intensity of hot spots may evolve by means of a concerted mechanism that maintains the overall recombination intensity in the region.

  1. Mapping a gene that determines erythrocytic GTP concentration to a region of mouse chromosome 9 which is syntenic to human chromosome 3p

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, F.F.; Jenuth, J.P.; Noy, J.L. [Univ. of Calgary, Alberta (Canada)] [and others

    1994-09-01

    Inbred mouse strains were surveyed for erythrocytic GTP concentration by high performance liquid chromatography and found to fall into two groups. Strains having low GTP levels between 1.4-3.4 nmole/10{sup 9} cells are represented by C3H/HeJ. Strains having high GTP levels between 11.0 - 14.8 nmole/10{sup 9} cells are represented by C57BL/6J. Erythocytic ATP levels did not vary significantly among these strains (63-87 nmole/10{sup 9} cells). Crosses between low and high GTP strains gave F{sub 1} progeny having intermediate levels of GTP. The progeny of F{sub 1}`s backcrossed to paternal strains segregated in a 1:1 ratio for GTP concentration characteristic of the F{sub 1} and parental strain. We designated the GTP concentration-determining trait Gtpc. Typing of the twelve BXH recombinant inbred strains revealed 0/12 strain distribution pattern differences with Gtpc for loci on both chromosomes 5 and 9. Backcross analysis did not provide evidence for linkage of Gtpc to W (dominant white spotting) on chromosome 5 with 15/45 recombinants. Backcross analysis testing for linkage of Gtpc to transferrin (Trf) on chromosome 9 gave evidence for linkage with a recombination frequency of 9.68 {plus_minus} 3.07. DNA-based typing of repeat length polymorphic markers on chromosome 9 gave a map distance of 10.7 {plus_minus} 3.6 between D9 MITl4 and Gtpc and placed Gtpc on the telomeric side of Trf. This region of mouse chromosome 9 is syntenic to human chromosome 3p and encompasses a cluster of G-protein loci.

  2. Conserved gene arrangement in the origin region of the Streptomyces coelicolor chromosome.

    Science.gov (United States)

    Calcutt, M J; Schmidt, F J

    1992-01-01

    A 23-kb fragment of the Streptomyces coelicolor chromosome spanning the dnaA region has been isolated as a cosmid clone. Nucleotide sequence analysis of a 5-kb portion shows that the genes for the RNase P protein (rnpA), ribosomal protein L34 (rpmH), the replication initiator protein (dnaA), and the beta subunit of DNA polymerase III (dnaN) are present in the highly conserved gene arrangement found in all eubacterial genomes studied so far. The dnaA-dnaN intergenic region is approximately 1 kb and contains a cluster of at least 12 DnaA boxes with a consensus sequence of TTGTCCACA matching the consensus DnaA box in the phylogenetically related Micrococcus luteus. Two DnaA boxes precede the dnaA sequence. We propose that the chromosomal origin (oriC) of S. coelicolor lies between dnaA and dnaN. In related work, J. Zakrzewska-Czerwinska and H. Schrempf (J. Bacteriol. 174:2688-2693, 1992) have identified the homologous sequence from the closely-related Streptomyces lividans as capable of self-replication. PMID:1577691

  3. Pancreaticoduodenectomy for advanced gastric cancer with pancreaticoduodenal region involvement

    Institute of Scientific and Technical Information of China (English)

    Xin-Bao Wang; Li-Tao Yang; Ze-Wei Zhang; Jian-Min Guo; Xiang-Dong Cheng

    2008-01-01

    AIM:To characterize the factors of the improved survival following combined pancreaticoduodenectomy (PD) and gastrectomy for the treatment of advanced gastric cancer with pancreaticoduodenal region involvement. METHODS:From 1995 to 2004,53 patients with primary gastric cancer were diagnosed with synchronous (n=44) or metachronous (n=9) pancreaticoduodenal region involvement.Of these,17 patients (32%) underwent total gastrectomy (TG) or distal subtotal gastrectomy (SG) combined with PD simultaneously.The preoperative demographic,clinical information,clinicopathologic features and the surgical results of these 17 patients were considered as factors influencing survival and were analyzed by the Kaplan-Meier method with log-rank comparison. RESULTS:The actual 1-and 3-year survival rates of these 17 patients after resection were 77% and 34%, respectively,and three patients survived for more than 5 years after surgery.The tumor-free resection margin (P=0.0174) and a well-differentiated histologic type (P=0.0011) were significant prognostic factors on univariate analysis.No mortality occurred within one mo after operation,postoperative weight loss of different degree was present in all the patients with TG and 12 cases had other complications.There were 9(53%) cases of recurrence in 5-48 mo after operation.The survival rate in the palliative and explorative group was significantly (P=0.0064) lower than in the combined PD group. CONCLUSION:Judicious use of en bloc PD and gastrectomy and strictly preventing postoperative complications may improve the long-term survival for advanced gastric cancer patients with pancreaticoduodenal region involvement.Well-differentiated histology and negative resection margin are the most important predictors of long survival.

  4. Chromosome region-specific libraries for human genome analysis. Final progress report, 1 March 1991--28 February 1994

    Energy Technology Data Exchange (ETDEWEB)

    Kao, F.T.

    1994-04-01

    The objectives of this grant proposal include (1) development of a chromosome microdissection and PCR-mediated microcloning technology, (2) application of this microtechnology to the construction of region-specific libraries for human genome analysis. During this grant period, the authors have successfully developed this microtechnology and have applied it to the construction of microdissection libraries for the following chromosome regions: a whole chromosome 21 (21E), 2 region-specific libraries for the long arm of chromosome 2, 2q35-q37 (2Q1) and 2q33-q35 (2Q2), and 4 region-specific libraries for the entire short arm of chromosome 2, 2p23-p25 (2P1), 2p21-p23 (2P2), 2p14-p16 (wP3) and 2p11-p13 (2P4). In addition, 20--40 unique sequence microclones have been isolated and characterized for genomic studies. These region-specific libraries and the single-copy microclones from the library have been used as valuable resources for (1) isolating microsatellite probes in linkage analysis to further refine the disease locus; (2) isolating corresponding clones with large inserts, e.g. YAC, BAC, P1, cosmid and phage, to facilitate construction of contigs for high resolution physical mapping; and (3) isolating region-specific cDNA clones for use as candidate genes. These libraries are being deposited in the American Type Culture Collection (ATCC) for general distribution.

  5. Transcriptional organization of a 450-kb region of the human X chromosome in Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Bione, S.; Tamanini, F.; Maestrini, E.; Tribioli, C.; Rivella, S.; Toniolo, D. (Instituto di Genetica Biochimica ed Evoluzionistica, Pavia (Italy)); Poustka, A. (German Cancer Research Center, Heidelberg (Germany))

    1993-11-15

    In this paper, the authors report the transcriptional organization of a 450-kb gene cluster in Xq28, flanked by the glucose-6-phosphate dehydrogenase and the color vision genes. CpG islands previously identified and mapped to distal Xq28 have helped in construction of a continuous contig of cosmids and in identification of cDNAs corresponding to eight transcripts. Thirteen to 16 small genes with CpG islands are clustered in a region of 250-300 kb. Many are highly expressed in muscle or brain and may be the genes responsible for muscle or neurological disorders mapped to distal Xq28. The analysis indicates that, in this region of the genome, genes not related in sequence are organized in transcriptional domains of 100 kb and that this organization may be important for establishing and regulating gene expression in relation to tissue distribution and X chromosome inactivation.

  6. Transcriptional organization of a 450-kb region of the human X chromosome in Xq28.

    Science.gov (United States)

    Bione, S; Tamanini, F; Maestrini, E; Tribioli, C; Poustka, A; Torri, G; Rivella, S; Toniolo, D

    1993-12-01

    In this paper, we report the transcriptional organization of a 450-kb gene cluster in Xq28, flanked by the glucose-6-phosphate dehydrogenase and the color vision genes. CpG islands previously identified and mapped to distal Xq28 have helped in construction of a continuous contig of cosmids and in identification of cDNAs corresponding to eight transcripts. Thirteen to 16 small genes with CpG islands are clustered in a region of 250-300 kb. Many are highly expressed in muscle or brain and may be the genes responsible for muscle or neurological disorders mapped to distal Xq28. Our analysis indicates that, in this region of the genome, genes not related in sequence are organized in transcriptional domains of 100 kb and that this organization may be important for establishing and regulating gene expression in relation to tissue distribution and X chromosome inactivation.

  7. NOR sites detected by Ag-dAPI staining of an unusual autosome chromosome of Bradysia hygida (Diptera:Sciaridae) colocalize with C-banded heterochromatic region.

    Science.gov (United States)

    Gaspar, Vanessa Pinatto; Borges, Alex Rodrigues; Fernandez, Maria Aparecida

    2002-01-01

    The study of chromosomes in insects is a good tool in mitotic process analysis, zoographic localization and evolution investigation. Among them, the Sciaridae offers a karyotype with a small number of chromosomes, where the heterochromatin and nucleolar organizer region, NOR, are easily analyzed in metaphase chromosomes obtained from cerebral ganglia squashes. In this work, the heterochromatic regions on Bradysia hygida mitotic chromosomes, revealed by C-banding, were identified as centromeric blocks on A and C chromosomes and as dark interstitial region in B and X chromosomes. By Ag-DAPI staining, active nucleolus organizer region, NOR, was revealed associated to the constitutive heterochromatin in the end of the C autosome chromosome. The C-band regions and the unusual ribosomal site localization are discussed.

  8. In silico prediction of structure and functions for some proteins of male-specific region of the human Y chromosome.

    Science.gov (United States)

    Saha, Chinmoy; Polash, Ahsan Habib; Islam, Md Tariqul; Shafrin, Farhana

    2013-12-01

    Male-specific region of the human Y chromosome (MSY) comprises 95% of its length that is functionally active. This portion inherits in block from father to male offspring. Most of the genes in the MSY region are involved in male-specific function, such as sex determination and spermatogenesis; also contains genes probably involved in other cellular functions. However, a detailed characterization of numerous MSY-encoded proteins still remains to be done. In this study, 12 uncharacterized proteins of MSY were analyzed through bioinformatics tools for structural and functional characterization. Within these 12 proteins, a total of 55 domains were found, with DnaJ domain signature corresponding to be the highest (11%) followed by both FAD-dependent pyridine nucleotide reductase signature and fumarate lyase superfamily signature (9%). The 3D structures of our selected proteins were built up using homology modeling and the protein threading approaches. These predicted structures confirmed in detail the stereochemistry; indicating reasonably good quality model. Furthermore the predicted functions and the proteins with whom they interact established their biological role and their mechanism of action at molecular level. The results of these structure-functional annotations provide a comprehensive view of the proteins encoded by MSY, which sheds light on their biological functions and molecular mechanisms. The data presented in this study may assist in future prognosis of several human diseases such as Turner syndrome, gonadal sex reversal, spermatogenic failure, and gonadoblastoma.

  9. A region of euchromatin coincides with an extensive tandem repeat on the mouse (Mus musculus) inactive X chromosome.

    Science.gov (United States)

    Darrow, Emily M; Seberg, Andrew P; Das, Sunny; Figueroa, Debbie M; Sun, Zhuo; Moseley, Shawn C; Chadwick, Brian P

    2014-09-01

    Euchromatic features are largely absent from the human inactive X chromosome (Xi), with the exception of several large tandem repeats that can be detected as euchromatin bands at metaphase. Despite residing megabases apart, these tandem repeats make frequent inactive X-specific interactions. The mouse homologue has been reported for at least one of the tandem repeats, but whether the mouse Xi is also characterized by distinct bands of euchromatin remains unknown. We examined the mouse Xi for the presence of euchromatin bands by examining the pattern of histone H3 dimethylated at lysine 4 and detected two major signals. The first band resides in the subtelomeric region of band XF5 and may correspond to the pseudoautosomal region. The second band localizes to XE3 and coincides with an extensive complex repeat composed of a large tandem and inverted repeat segment as well as several large short interspersed nuclear element (SINE)-rich tandem repeats. Fluorescence in situ hybridization reveals that sequences with homology to the repeat region are scattered along the length of the Y chromosome. Immunofluorescence analysis of histone H3 trimethylated at lysine 9 on metaphase chromosomes indicates that the repeat region corresponds to a band of constitutive heterochromatin on the male X and female active X chromosomes, whereas the euchromatin signal appears to be female specific. These data suggest that the band of euchromatin observed at XE3 is unique to the mouse Xi, comparable to the chromatin arrangement of several large tandem repeats located on the human X chromosome.

  10. Investigation of the chromosome regions with significant affinity for the nuclear envelope in fruit fly--a model based approach.

    Directory of Open Access Journals (Sweden)

    Nicholas Allen Kinney

    Full Text Available Three dimensional nuclear architecture is important for genome function, but is still poorly understood. In particular, little is known about the role of the "boundary conditions"--points of attachment between chromosomes and the nuclear envelope. We describe a method for modeling the 3D organization of the interphase nucleus, and its application to analysis of chromosome-nuclear envelope (Chr-NE attachments of polytene (giant chromosomes in Drosophila melanogaster salivary glands. The model represents chromosomes as self-avoiding polymer chains confined within the nucleus; parameters of the model are taken directly from experiment, no fitting parameters are introduced. Methods are developed to objectively quantify chromosome territories and intertwining, which are discussed in the context of corresponding experimental observations. In particular, a mathematically rigorous definition of a territory based on convex hull is proposed. The self-avoiding polymer model is used to re-analyze previous experimental data; the analysis suggests 33 additional Chr-NE attachments in addition to the 15 already explored Chr-NE attachments. Most of these new Chr-NE attachments correspond to intercalary heterochromatin--gene poor, dark staining, late replicating regions of the genome; however, three correspond to euchromatin--gene rich, light staining, early replicating regions of the genome. The analysis also suggests 5 regions of anti-contact, characterized by aversion for the NE, only two of these correspond to euchromatin. This composition of chromatin suggests that heterochromatin may not be necessary or sufficient for the formation of a Chr-NE attachment. To the extent that the proposed model represents reality, the confinement of the polytene chromosomes in a spherical nucleus alone does not favor the positioning of specific chromosome regions at the NE as seen in experiment; consequently, the 15 experimentally known Chr-NE attachment positions do not

  11. Involvement of condensin-directed gene associations in the organization and regulation of chromosome territories during the cell cycle

    Science.gov (United States)

    Iwasaki, Osamu; Corcoran, Christopher J.; Noma, Ken-ichi

    2016-01-01

    Chromosomes are not randomly disposed in the nucleus but instead occupy discrete sub-nuclear domains, referred to as chromosome territories. The molecular mechanisms that underlie the formation of chromosome territories and how they are regulated during the cell cycle remain largely unknown. Here, we have developed two different chromosome-painting approaches to address how chromosome territories are organized in the fission yeast model organism. We show that condensin frequently associates RNA polymerase III-transcribed genes (tRNA and 5S rRNA) that are present on the same chromosomes, and that the disruption of these associations by condensin mutations significantly compromises the chromosome territory arrangement. We also find that condensin-dependent intra-chromosomal gene associations and chromosome territories are co-regulated during the cell cycle. For example, condensin-directed gene associations occur to the least degree during S phase, with the chromosomal overlap becoming largest. In clear contrast, condensin-directed gene associations become tighter in other cell-cycle phases, especially during mitosis, with the overlap between the different chromosomes being smaller. This study suggests that condensin-driven intra-chromosomal gene associations contribute to the organization and regulation of chromosome territories during the cell cycle. PMID:26704981

  12. Forensic analysis of polymorphism and regional stratification of Y-chromosomal microsatellites in Belarus.

    Science.gov (United States)

    Rebała, Krzysztof; Tsybovsky, Iosif S; Bogacheva, Anna V; Kotova, Svetlana A; Mikulich, Alexei I; Szczerkowska, Zofia

    2011-01-01

    Nine loci defining minimal haplotypes and four other Y-chromosomal short tandem repeats (Y-STRs) DYS437, DYS438, DYS439 and GATA H4.1 were analysed in 414 unrelated males residing in four regions of Belarus. Haplotypes of 328 males were further extended by 7 additional Y-STRs: DYS388, DYS426, DYS448, DYS456, DYS458, DYS460 and DYS635. The 13-locus haplotype diversity was 0.9978 and discrimination capacity was 78.7%, indicating presence of identical haplotypes among unrelated males. Seven additional Y-STRs enabled almost complete discrimination of undifferentiated 13-locus haplotypes, increasing haplotype diversity to 0.9998 and discrimination capacity to 97.9%. Analysis of molecular variance of minimal haplotypes excluded the use of a Y-STR database for Belarusians residing in northeastern Poland as representative for the Belarusian population in forensic practice, and revealed regional stratification within the country. However, four additional markers (DYS437, DYS438, DYS439 and GATA H4.1) were shown to eliminate the observed geographical substructure among Belarusian males. The results imply that in case of minimal and PowerPlex Y haplotypes, a separate frequency database should be used for northern Belarus to estimate Y-STR profile frequencies in forensic casework. In case of Yfiler haplotypes, regional stratification within Belarus may be neglected.

  13. Deletion and duplication within the p11.2 region of chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    McCorquodale, D.J.; McCorquodale, M.; Bereziouk, O. [Univ. of Illinois College of Medicine, Chicago, IL (United States)] [and others

    1994-09-01

    A 7 1/2-year-old male patient presented with mild mental retardation, speech delay, hyperactivity, behavioral problems, mild facial hypoplasia, short broad hands, digital anomalies, and self-injurious behavior. Chromosomes obtained from peripheral blood cells revealed a deletion of 17p11.2 in about 40% of the metaphases examined, suggesting that the patient had Smith-Magenis Syndrome. A similar pattern of mosaicism in peripheral blood cells, but not in fibroblasts in which all cells displayed the deletion, has been previously reported. Since some cases of Smith-Magenis Syndrome have a deletion that extends into the region associated with Charcot-Marie-Tooth (CMT) Syndrome, we examined interphase cells with a CMT1A-specific probe by the method of fluorescence in situ hybridization. The CMT1A region was not deleted, but about 40% of the cells gave signals indicating a duplication of the CMT1A region. The patient has not presented neuropathies associated with CMT at this time. Future tracking of the patient should be informative.

  14. Aneuploidy involving chromosome 1 may be an early predictive marker of intestinal type gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Williams, L. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Somasekar, A. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Davies, D.J.; Cronin, J.; Doak, S.H. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Alcolado, R. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Williams, J.G. [Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Griffiths, A.P. [Department of Histopathology, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Baxter, J.N. [Department of Surgery, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Jenkins, G.J.S., E-mail: g.j.jenkins@swansea.ac.uk [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom)

    2009-10-02

    Intestinal type gastric cancer is a significant cause of mortality, therefore a better understanding of its molecular basis is required. We assessed if either aneuploidy or activity of the oncogenic transcription factor nuclear factor kappa B (NF-{kappa}B), increased incrementally during pre-malignant gastric histological progression and also if they correlated with each other in patient samples, as they are both induced by oxygen free radicals. In a prospective study of 54 (aneuploidy) and 59 (NF-{kappa}B) consecutive patients, aneuploidy was assessed by interphase fluorescent in situ hybridisation (FISH) for chromosome 1. NF-{kappa}B was assessed by expression of interleukin-8 (IL-8), and in a subset, by immunohistochemistry (IHC) for active p65. Aneuploidy levels increased incrementally across the histological series. 2.76% of cells with normal histology (95% CI, 2.14-3.38%) showed background levels of aneuploidy, this increased to averages of 3.78% (95% CI, 3.21-4.35%), 5.89% (95% CI, 3.72-8.06%) and 7.29% (95% CI, 4.73-9.85%) of cells from patients with gastritis, Helicobacter pylori positive gastritis and atrophy/intestinal metaplasia (IM) respectively. IL-8 expression was only increased in patients with current H. pylori infection. NF-{kappa}B analysis showed some increased p65 activity in inflamed tissues. IL-8 expression and aneuploidy level were not linked in individual patients. Aneuploidy levels increased incrementally during histological progression; were significantly elevated at very early stages of neoplastic progression and could well be linked to cancer development and used to assess cancer risk. Reactive oxygen species (ROS) induced in early gastric cancer are presumably responsible for the stepwise accumulation of this particular mutation, i.e. aneuploidy. Hence, aneuploidy measured by fluorescent in situ hybridisation (FISH) coupled to brush cytology, would be worthy of consideration as a predictive marker in gastric cancer and could be

  15. Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and acrocentric heterochromatin in two families with chromosomal translocations.

    Science.gov (United States)

    Ou, Zhishuo; Jarmuz, Małgorzata; Sparagana, Steven P; Michaud, Jacques; Décarie, Jean-Claude; Yatsenko, Svetlana A; Nowakowska, Beata; Furman, Patti; Shaw, Chad A; Shaffer, Lisa G; Lupski, James R; Chinault, A Craig; Cheung, Sau W; Stankiewicz, Paweł

    2006-09-01

    We report clinical findings and molecular cytogenetic analyses for two patients with translocations [t(14;17)(p12;p12) and t(15;17)(p12;p13.2)], in which the chromosome 17 breakpoints map at a large low-copy repeat (LCR) and a breakage-prone TRE-2 (USP6) oncogene, respectively. In family 1, a 6-year-old girl and her 5-year-old brother were diagnosed with mental retardation, short stature, dysmorphic features, and Charcot-Marie-Tooth disease type 1A (CMT1A). G-banding chromosome analysis showed a der(14)t(14;17)(p12;p12) in both siblings, inherited from their father, a carrier of the balanced translocation. Chromosome microarray and FISH analyses revealed that the PMP22 gene was duplicated. The chromosome 17 breakpoint was mapped within an approximately 383 kb LCR17pA that is known to also be the site of several breakpoints of different chromosome aberrations including the evolutionary translocation t(4;19) in Gorilla gorilla. In family two, a patient with developmental delay, subtle dysmorphic features, ventricular enlargement with decreased periventricular white matter, mild findings of bilateral perisylvian polymicrogyria and a very small anterior commissure, a cryptic duplication including the Miller-Dieker syndrome region was identified by chromosome microarray analysis. The chromosome 17 breakpoint was mapped by FISH at the TRE-2 oncogene. Both partner chromosome breakpoints were mapped on the short arm acrocentric heterochromatin within or distal to the rRNA cluster, distal to the region commonly rearranged in Robertsonian translocations. We propose that TRE-2 together with LCR17pA, located approximately 10 Mb apart, also generated the evolutionary gorilla translocation t(4;19). Our results support previous observations that the USP6 oncogene, LCRs, and repetitive DNA sequences play a significant role in the origin of constitutional chromosome aberrations and primate genome evolution.

  16. Evaluation of single nucleotide polymorphisms in chromosomal regions impacting pregnancy status in cattle.

    Science.gov (United States)

    Psaros, K M; McDaneld, T G; Kuehn, L A; Snelling, W M; Keele, J W

    2015-03-01

    Reproductive success is an important component of commercial beef cattle production, and identification of DNA markers with predictive merit for reproductive success would facilitate accurate prediction of mean daughter pregnancy rate, enabling effective selection of bulls to improve female fertility. A previous study identified SNP associated with beef cattle reproductive efficiency based on a genomewide association analysis approach using genotyping multiple-animal pools of DNA to increase the number of animals that could be genotyped with available resources. For the current study, we expand on this previous study by individually genotyping cattle from the pooling study for 89 SNP that were associated with female pregnancy rate. The aims of the study were to confirm the results of the pooling study and, more specifically, identify modes of gene action and DNA variations such as haplotypes that would not be possible with pooled genotyping. Eighty-nine SNP selected from the pooling study were evaluated using the Sequenom MassARRAY system to individually genotype animals from populations evaluated in the pooling study, including both and breeds. From this research, regions on chromosomes 5 (26.3-48.1 Mb; UMD3.1 assembly) and 9 (37,436,575 bp; UMD3.1 assembly), first identified in the previous pooling study, were shown through individual genotyping to harbor genetic variation ( reproductive efficiency in interspecific crosses ( and ) of cattle. Each of these markers exhibited additive (vs. dominant) gene action. Additionally, a haplotype block harboring an allele of origin with negative effects on reproduction was identified on chromosome 5 in interspecific composite breeds of × composites.

  17. Homomorphic ZW chromosomes in a wild strawberry show distinctive recombination heterogeneity but a small sex-determining region.

    Science.gov (United States)

    Tennessen, Jacob A; Govindarajulu, Rajanikanth; Liston, Aaron; Ashman, Tia-Lynn

    2016-09-01

    Recombination in ancient, heteromorphic sex chromosomes is typically suppressed at the sex-determining region (SDR) and proportionally elevated in the pseudoautosomal region (PAR). However, little is known about recombination dynamics of young, homomorphic plant sex chromosomes. We examine male and female function in crosses and unrelated samples of the dioecious octoploid strawberry Fragaria chiloensis in order to map the small and recently evolved SDR controlling both traits and to examine recombination patterns on the incipient ZW chromosome. The SDR of this ZW system is located within a 280 kb window, in which the maternal recombination rate is lower than the paternal one. In contrast to the SDR, the maternal PAR recombination rate is much higher than the rates of the paternal PAR or autosomes, culminating in an elevated chromosome-wide rate. W-specific divergence is elevated within the SDR and a single polymorphism is observed in high species-wide linkage disequilibrium with sex. Selection for recombination suppression within the small SDR may be weak, but fluctuating sex ratios could favor elevated recombination in the PAR to remove deleterious mutations on the W. The recombination dynamics of this nascent sex chromosome with a modestly diverged SDR may be typical of other dioecious plants.

  18. Idiopathic cases of male infertility from a region in India show low incidence of Y-chromosome microdeletion

    Indian Academy of Sciences (India)

    R Ambasudhan; K Singh; J K Agarwal; S K Singh; A Khanna; R K Sah; I Singh; R Raman

    2003-09-01

    Chromosomal and Y-chromosomal microdeletion analysis has been done in cases of idiopathic infertility with the objective of evaluating the frequency of chromosomal and molecular anomaly as the causal factor of infertility. Barring a few cases of Klinefelter syndrome (XXY or XY/XXY mosaics), no chromosomal anomaly was encountered. Y-microdeletion was analysed by PCR-screening of STSs from different regions of the AZF (AZFa, AZFb, AZFc) on the long arm of the Y, as well as by using DNA probes of the genes RBM, DAZ (Yq), DAZLA (an autosomal homologue of DAZ) and SRY (Yp; sex determining gene). Out of 177 cases examined, 9 (azoospermia – 8 and oligoasthenospermia – 1) showed partial deletion of AZF. The size of deletion varied among patients but AZFc was either totally or partially removed in all of them. In contrast, no deletion was detected in AZFa. Testis biopsy done on a limited number of cases (50) showed diverse stages of spermatogenic arrest with no specific correlation with the genotype. The frequency of Y-chromosome microdeletion in our samples (∼ 5%) is much lower than the frequency (∼ 10%) reported globally and the two previous reports from India. We contend that the frequency may be affected by population structures in different geographical regions.

  19. Characterization and chromosomal mapping of the human TFG gene involved in thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Mencinger, M.; Panagopoulos, I.; Andreasson, P. [Univ. Hospital of Lund (Sweden)] [and others

    1997-05-01

    Homology searches in the Expressed Sequence Tag Database were performed using SPYGQ-rich regions as query sequences to find genes encoding protein regions similar to the N-terminal parts of the sarcoma-associated EWS and FUS proteins. Clone 22911 (T74973), encoding a SPYGQ-rich region in its 5{prime} end, and several other clones that overlapped 22911 were selected. The combined data made it possible to assemble a full-length cDNA sequence. This cDNA sequence is 1677 bp, containing an initiation codon ATG, an open reading frame of 400 amino acids, a poly(A) signal, and a poly(A) tail. We found 100% identity between the 5{prime} part of the consensus sequence and the 598-bp-long sequence named TFG. The TFG sequence is fused to the 3{prime} end of NTRK1, generating the TRK-T3 fusion transcript found in papillary thyroid carcinoma. The cDNA therefore represents the full-length transcript of the TFG gene. TFG was localized to 3q11-q12 by fluorescence in situ hybridization. The 3{prime} and the 5{prime} ends of the TFG cDNA probe hybridized to a 2.2-kb band on Northern blot filters in all tissues examined. 28 refs., 5 figs., 1 tab.

  20. Identification and characterization of genomic regions on chromosomes 4 and 8 that control the rate of photosynthesis in rice leaves.

    Science.gov (United States)

    Adachi, Shunsuke; Tsuru, Yukiko; Nito, Naoko; Murata, Kazumasa; Yamamoto, Toshio; Ebitani, Takeshi; Ookawa, Taiichiro; Hirasawa, Tadashi

    2011-03-01

    DNA marker-assisted selection appears to be a promising strategy for improving rates of leaf photosynthesis in rice. The rate of leaf photosynthesis was significantly higher in a high-yielding indica variety, Habataki, than in the most popular Japanese variety, Koshihikari, at the full heading stage as a result of the higher level of leaf nitrogen at the same rate of application of nitrogen and the higher stomatal conductance even when the respective levels of leaf nitrogen were the same. The higher leaf nitrogen content of Habataki was caused by the greater accumulation of nitrogen by plants. The higher stomatal conductance of Habataki was caused by the higher hydraulic conductance. Using progeny populations and selected lines derived from a cross between Koshihikari and Habataki, it was possible to identify the genomic regions responsible for the rate of photosynthesis within a 2.1 Mb region between RM17459 and RM17552 and within a 1.2 Mb region between RM6999 and RM22529 on the long arm of chromosome 4 and on the short arm of chromosome 8, respectively. The designated region on chromosome 4 of Habataki was responsible for both the increase in the nitrogen content of leaves and hydraulic conductance in the plant by increasing the root surface area. The designated region on chromosome 8 of Habataki was responsible for the increase in hydraulic conductance by increasing the root hydraulic conductivity. The results suggest that it may be possible to improve photosynthesis in rice leaves by marker-assisted selection that focuses on these regions of chromosomes 4 and 8.

  1. A high-resolution map of the chromosomal region surrounding the nude gene

    Energy Technology Data Exchange (ETDEWEB)

    Blackburn, C.C.; Griffith, J.; Morahan, G. [Royal Melbourne Hospital, Victoria (Australia)

    1995-03-20

    The nude mutation produces the apparently disparate phenotypes of hairlessness and congenital thymic aplasia. These pleiotropic defects are the result of a single, autosomal recessive mutation that was previously mapped to a 9-cM region of murine chromosome 11 bounded by loci encoding the acetylcholine receptor P subunit and myeloperoxidase. In this study, exclusion mapping of a panel of congenic nude strains was used to place the nude locus between the microsatellite loci D11Nds1 and D11Mit8. The relative distance from nude to each of these loci was determined by analyzing a large segregating cross. Thus, nude lies 1.4 cM distal to D11Nds1 and is 0.5 cM proximal to D11Mit8. Mice that carried recombinational breakpoints between D11Nds1 and D11Mit8 were further analyzed at the loci Evi-2 and D11Mit34, which placed nu 0.2 cM proximal to these markers. D11Nds1 and Evi-2/D11Mit34 thus define the new proximal and distal boundaries, respectively, for the nu interval. We also report the typing of the above microsatellite markers in the AKXD, AKXL, BXD, CXB, and BXH recombinant inbred strains, which confirmed the relative order and separation of loci in this region. 47 refs., 3 figs., 1 tab.

  2. Strong selective sweeps associated with ampliconic regions in great ape X chromosomes

    DEFF Research Database (Denmark)

    Nam, Kiwoong; Munch, Kasper; Hobolth, Asger

    2014-01-01

    The unique inheritance pattern of X chromosomes makes them preferential targets of adaptive evolution. We here investigate natural selection on the X chromosome in all species of great apes. We find that diversity is more strongly reduced around genes on the X compared with autosomes, and that a ......The unique inheritance pattern of X chromosomes makes them preferential targets of adaptive evolution. We here investigate natural selection on the X chromosome in all species of great apes. We find that diversity is more strongly reduced around genes on the X compared with autosomes...

  3. [Sex chromosomes and meiosis].

    Science.gov (United States)

    Guichaoua, M-R; Geoffroy-Siraudin, C; Tassistro, V; Ghalamoun-Slaimi, R; Perrin, J; Metzler-Guillemain, C

    2009-01-01

    Sex chromosome behaviour fundamentally differs between male and female meiosis. In oocyte, X chromosomes synapse giving a XX bivalent which is not recognizable in their morphology and behaviour from autosomal bivalents. In human male, X and Y chromosomes differ from one another in their morphology and their genetic content, leading to a limited pairing and preventing genetic recombination, excepted in homologous region PAR1. During pachytene stage of the first meiotic prophase, X and Y chromosomes undergo a progressive condensation and form a transcriptionally silenced peripheral XY body. The condensation of the XY bivalent during pachytene stage led us to describe four pachytene substages and to localize the pachytene checkpoint between substages 2 and 3. We also defined the pachytene index (PI=P1+P2/P1+P2+P3+P4) which is always less than 0.50 in normal meiosis. XY body undergoes decondensation at diplotene stage, but transcriptional inactivation of the two sex chromosomes or Meiotic Sex Chromosome Inactivation (MSCI) persists through to the end of spermatogenesis. Sex chromosome inactivation involves several proteins, some of them were now identified. Two isoforms of the HP1 protein, HP1beta and HP1gamma, are involved in the facultative heterochromatinization of the XY body, but the initiation of this process involves the phosphorylation of the protein H2AX by the kinase ATR whose recruitment depends on BRCA1. Extensive researches on the inactivation of the sex chromosomes during male meiosis will allow to a better understanding of some male infertilities.

  4. Differential repetitive DNA composition in the centromeric region of chromosomes of Amazonian lizard species in the family Teiidae.

    Science.gov (United States)

    Carvalho, Natalia D M; Carmo, Edson; Neves, Rogerio O; Schneider, Carlos Henrique; Gross, Maria Claudia

    2016-01-01

    Differences in heterochromatin distribution patterns and its composition were observed in Amazonian teiid species. Studies have shown repetitive DNA harbors heterochromatic blocks which are located in centromeric and telomeric regions in Ameiva ameiva (Linnaeus, 1758), Kentropyx calcarata (Spix, 1825), Kentropyx pelviceps (Cope, 1868), and Tupinambis teguixin (Linnaeus, 1758). In Cnemidophorus sp.1, repetitive DNA has multiple signals along all chromosomes. The aim of this study was to characterize moderately and highly repetitive DNA sequences by C ot1-DNA from Ameiva ameiva and Cnemidophorus sp.1 genomes through cloning and DNA sequencing, as well as mapping them chromosomally to better understand its organization and genome dynamics. The results of sequencing of DNA libraries obtained by C ot1-DNA showed that different microsatellites, transposons, retrotransposons, and some gene families also comprise the fraction of repetitive DNA in the teiid species. FISH using C ot1-DNA probes isolated from both Ameiva ameiva and Cnemidophorus sp.1 showed these sequences mainly located in heterochromatic centromeric, and telomeric regions in Ameiva ameiva, Kentropyx calcarata, Kentropyx pelviceps, and Tupinambis teguixin chromosomes, indicating they play structural and functional roles in the genome of these species. In Cnemidophorus sp.1, C ot1-DNA probe isolated from Ameiva ameiva had multiple interstitial signals on chromosomes, whereas mapping of C ot1-DNA isolated from the Ameiva ameiva and Cnemidophorus sp.1 highlighted centromeric regions of some chromosomes. Thus, the data obtained showed that many repetitive DNA classes are part of the genome of Ameiva ameiva, Cnemidophorus sp.1, Kentroyx calcarata, Kentropyx pelviceps, and Tupinambis teguixin, and these sequences are shared among the analyzed teiid species, but they were not always allocated at the same chromosome position.

  5. Sex and age specific effects of chromosomal regions linked to body mass index in the Framingham Study

    Directory of Open Access Journals (Sweden)

    Fox Caroline S

    2006-01-01

    Full Text Available Abstract Background Previously, we reported significant linkage of body mass index (BMI to chromosomes 6 and 11 across six examinations, covering 28 years, of the Framingham Heart Study. These results were on all individuals available at each exam, thus the sample size varied from exam to exam. To remove any effect of sample size variation we have now constructed six subsets; for each exam individuals were only included if they were measured at every exam, i.e. for each exam, included individuals comprise the intersection of the original six exams. This strategy preferentially removed older individuals who died before reaching the sixth exam, thus the intersection datasets are smaller (n = 1114 and significantly younger than the full datasets. We performed variance components linkage analysis on these intersection datasets and on their sex-specific subsets. Results Results from the sex-specific genome scans revealed 11 regions in which a sex-specific maximum lodscore was at least 2.0 for at least one dataset. Randomization tests indicated that all 11 regions had significant (p Results from the full genome scans revealed that linked regions on chromosomes 6 and 11 remained significantly and consistently linked in the intersection datasets. Surprisingly, the maximum lodscore on chromosome 10 for dataset 1 increased from 0.97 in the older original dataset to 4.23 in the younger smaller intersection dataset. This difference in maximum lodscores was highly significant (p Conclusion Sex specific effects of chromosomal regions on BMI are common in the Framingham study. Some evidence also exists for age-specific effects of chromosomal regions.

  6. Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer.

    Science.gov (United States)

    Kluth, Martina; Galal, Rami; Krohn, Antje; Weischenfeldt, Joachim; Tsourlakis, Christina; Paustian, Lisa; Ahrary, Ramin; Ahmed, Malik; Scherzai, Sekander; Meyer, Anne; Sirma, Hüseyin; Korbel, Jan; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Minner, Sarah

    2015-04-01

    Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were unrelated to ETS genes in 11 prostate cancers. The aim of the present study was to estimate the prevalence of non-ETS gene fusions. We randomly selected 27 of these rearrangements and analyzed them by fluorescence in situ hybridization (FISH) in a tissue microarray format containing 500 prostate cancers. Using break-apart FISH probes for one fusion partner each, we found rearrangements of 13 (48%) of the 27 analyzed genes in 300-400 analyzable cancers per gene. Recurrent breakage, often accompanied by partial deletion of the genes, was found for NCKAP5, SH3BGR and TTC3 in 3 (0.8%) tumors each, as well as for ARNTL2 and ENOX1 in 2 (0.5%) cancers each. One rearranged tumor sample was observed for each of VCL, ZNF578, IMMP2L, SLC16A12, PANK1, GPHN, LRP1 and ZHX2. Balanced rearrangements, indicating possible gene fusion, were found for ZNF578, SH3BGR, LPR12 and ZHX2 in individual cancers only. The results of the present study confirm that rearrangements involving non-ETS genes occur in prostate cancer, but demonstrate that they are highly individual and typically non-recurrent.

  7. The Involvement of Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN in the Regulation of Inflammation Following Coronary Microembolization

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    Jiangyou Wang

    2014-06-01

    Full Text Available Background/Aims: Growing evidence shows that phosphatase and tensin homolog deleted on chromosome ten (PTEN is involved in regulating inflammation in different pathological conditions. Therefore, we hypothesized that the upregulation of PTEN correlates with the impairment of cardiac function in swine following coronary microembolization (CME. Methods: To possibly disclose an anti-inflammatory effect of PTEN, we induced swine CME by injecting inertia plastic microspheres (42 μm in diameter into the left anterior descending coronary artery and analyzed the myocardial tissue by immunochemistry, qRT-PCR and western blot analyses. In addition, we downregulated PTEN using siRNA. Results: Following CME, PTEN mRNA and protein levels were elevated as early as 3 h, peaked at 12 h, and then continuously decreased at 24 h and 48 h but remained elevated. Through linear correlation analysis, the PTEN protein level positively correlated with cTnI and TNF-α but was negatively correlated with LVEF. Furthermore, PTEN siRNA reduced the microinfarct volume, improved cardiac function (LVEF, reduced the release of cTnI, and suppressed PTEN and TNF-α protein expression. Conclusion: This study demonstrated, for the first time, that PTEN is involved in CME-induced inflammatory injury. The data generated from this study provide a rationale for the development of PTEN-based anti-inflammatory strategies.

  8. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

    2016-05-24

    Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

  9. AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants.

    Science.gov (United States)

    Ruiz, José F; Gómez-González, Belén; Aguilera, Andrés

    2011-02-01

    Transcription of the switch (S) regions of immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID), triggering class switch recombination (CSR), as well as translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, stable R-loops are formed co-transcriptionally in mutants of THO, a conserved nuclear complex involved in mRNP biogenesis. Such R-loops trigger genome instability and facilitate deamination by human AID. To understand the mechanisms that generate genome instability mediated by mRNP biogenesis impairment and by AID, we devised a yeast chromosomal system based on different segments of mammalian S regions and c-MYC for the analysis of chromosomal rearrangements in both wild-type and THO mutants. We demonstrate that AID acts in yeast at heterologous S and c-MYC transcribed sequences leading to double-strand breaks (DSBs) which in turn cause chromosomal translocations via Non-Homologous End Joining (NHEJ). AID-induced translocations were strongly enhanced in yeast THO null mutants, consistent with the idea that AID-mediated DSBs depend on R-loop formation. Our study not only provides new clues to understand the role of mRNP biogenesis in preventing genome rearrangements and the mechanism of AID-mediated genome instability, but also shows that, once uracil residues are produced by AID-mediated deamination, these are processed into DSBs and chromosomal rearrangements by the general and conserved DNA repair functions present from yeast to human cells.

  10. AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants.

    Directory of Open Access Journals (Sweden)

    José F Ruiz

    2011-02-01

    Full Text Available Transcription of the switch (S regions of immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID, triggering class switch recombination (CSR, as well as translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, stable R-loops are formed co-transcriptionally in mutants of THO, a conserved nuclear complex involved in mRNP biogenesis. Such R-loops trigger genome instability and facilitate deamination by human AID. To understand the mechanisms that generate genome instability mediated by mRNP biogenesis impairment and by AID, we devised a yeast chromosomal system based on different segments of mammalian S regions and c-MYC for the analysis of chromosomal rearrangements in both wild-type and THO mutants. We demonstrate that AID acts in yeast at heterologous S and c-MYC transcribed sequences leading to double-strand breaks (DSBs which in turn cause chromosomal translocations via Non-Homologous End Joining (NHEJ. AID-induced translocations were strongly enhanced in yeast THO null mutants, consistent with the idea that AID-mediated DSBs depend on R-loop formation. Our study not only provides new clues to understand the role of mRNP biogenesis in preventing genome rearrangements and the mechanism of AID-mediated genome instability, but also shows that, once uracil residues are produced by AID-mediated deamination, these are processed into DSBs and chromosomal rearrangements by the general and conserved DNA repair functions present from yeast to human cells.

  11. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae).

    Science.gov (United States)

    Vijverberg, K; Van Der Hulst, R G M; Lindhout, P; Van Dijk, P J

    2004-02-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The genus includes sexual diploid as well as apomictic polyploid, mostly triploid, plants. Apomictic Taraxacum is diplosporous, parthenogenetic, and has autonomous endosperm formation. Previous studies have indicated that these three apomixis elements are controlled by more than one locus in Taraxacum and that diplospory inherits as a dominant, monogenic trait ( Ddd; DIP). A bulked segregant analysis provided 34 AFLP markers that were linked to DIP and were, together with two microsatellite markers, used for mapping the trait. The map length was 18.6 cM and markers were found on both sides of DIP, corresponding to 5.9 and 12.7 cM, respectively. None of the markers completely co-segregated with DIP. Eight markers were selected for PCR-based marker development, of which two were successfully converted. In contrast to all other mapping studies of apomeiosis to date, our results showed no evidence for suppression of recombination around the DIP locus in Taraxacum. No obvious evidence for sequence divergence between the DIP and non- DIP homologous loci was found, and no hemizygosity at the DIP locus was detected. These results may indicate that apomixis is relatively recent in Taraxacum.

  12. Dissecting the transcriptional regulatory properties of human chromosome 16 highly conserved non-coding regions.

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    José Luis Royo

    Full Text Available Non-coding DNA conservation across species has been often used as a predictor for transcriptional enhancer activity. However, only a few systematic analyses of the function of these highly conserved non-coding regions (HCNRs have been performed. Here we use zebrafish transgenic assays to perform a systematic study of 113 HCNRs from human chromosome 16. By comparing transient and stable transgenesis, we show that the first method is highly inefficient, leading to 40% of false positives and 20% of false negatives. When analyzed in stable transgenic lines, a great majority of HCNRs were active in the central nervous system, although some of them drove expression in other organs such as the eye and the excretory system. Finally, by testing a fraction of the HCNRs lacking enhancer activity for in vivo insulator activity, we find that 20% of them may contain enhancer-blocking function. Altogether our data indicate that HCNRs may contain different types of cis-regulatory activity, including enhancer, insulators as well as other not yet discovered functions.

  13. Nucleolar organizer regions and a new chromosome number for Rhea americana (Aves: Rheiformes

    Directory of Open Access Journals (Sweden)

    Ricardo José Gunski

    1998-06-01

    Full Text Available Sequential banding analysis (Giemsa-C-banding-Ag NOR of chromosomes of the common rhea (Rhea americana was performed. Metaphases were obtained by peripheral blood lymphocyte culture and monolayer embryo cell culture. The diploid chromosome number was 80, different from the 2n = 82 in previous reports. Macrochromosome pairs 1, 2 and 5 were submetacentric and pair 3, subacrocentric. The 4th pair was acrocentric and all of the microchromosomes appeared to be acrocentric, with the exception of a clearly metacentric pair which was fully heterochromatic. The Z was slightly larger than the W, both being acrocentric and C-band negative. Nucleolar organizer regions were observed in the secondary constriction of a microchromosome pair. Correct identification of the NOR-bearing pair was possible only by sequential analyses, Giemsa staining followed by the Ag-NOR technique.Foram efetuadas análises seqüenciais de bandeamento cromossômico (Giemsa-banda-C-AgNOR em material da espécie Rhea americana (ema com o objetivo de identificar os cromossomos portadores de regiões organizadoras de nucléolos e confirmar o cariótipo desta espécie. As metáfases foram obtidas de culturas de leucócitos e de células de embrião. O número diplóide de cromossomos, determinado pela análise de metáfases oriundas de 19 espécimes, foi de 80 (2n = 80, NF = 95, o que difere da literatura. Os pares de macrocromossomos números 1, 2 e 5 eram submetacêntricos e o par 3 era sub-acrocêntrico, confirmado pelo bandeamento C. O par 4 era acrocêntrico, bem como todos os microcromossomos, com exceção de um metacêntrico inteiramente heterocromático. O cromossomo Z era ligeiramente maior que o W, sendo ambos acrocêntricos e banda-C negativos. A região organizadora de nucléolos foi observada na constrição secundária de um par de microcromossomos. A correta identificação do par portador da NOR só foi possível com a utilização da análise seqüencial de colora

  14. Generation of an integrated transcription map of the BRCA2 region on chromosome 13q12-q13

    Energy Technology Data Exchange (ETDEWEB)

    Couch, F.J.; Peng, Yi; Thakur, Sanjay [Univ. of Pennsylvania, Philadelphia, PA (United States)] [and others

    1996-08-15

    An integrated approach involving physical mapping, identification of transcribed sequences, and computational analysis of genomic sequence was used to generate a detailed transcription map of the 1.0-Mb region containing the breast cancer susceptibility locus BRCA2 on chromosome 13q12-q13. This region is included in the genetic interval bounded by D13S1444 and D13S310. Retrieved sequences from exon amplification or hybrid selection procedures were grouped into physical intervals and subsequently grouped into transcription units by clone overlap. Overlap was established by direct hybridization, cDNA library screening, PCR cDNA linking (island hopping), and/or sequence alignment. Extensive genomic sequencing was performed in an effort to understand transcription unit organization. In total, approximately 500 kb of genomic sequence was completed. The transcription units were further characterized by hybridization to RNA from a series of human tissues. Evidence for seven genes, two putative pseudogenes, and nine additional putative transcription units was obtained. One of the transcription units was recently identified as BRCA2 but all others are novel genes of unknown function as only limited alignment to sequences in public databases was observed. Several retrieved transcribed sequences were not aligned into transcription units because no corresponding cDNAs were obtained when screening libraries or because of a lack of definitive evidence for splicing signals or putative coding sequence based on computational analysis. However, the presence of additional genes in the BRCA2 interval is suggested as groups of putative exons and hybrid selected clones that were transcribed in consistent orientations could be localized to common physical intervals. 25 refs., 2 figs., 3 tabs.

  15. Loss of chromosome 1p/19q in oligodendroglial tumors: refinement of chromosomal critical regions and evaluation of internexin immunostaining as a surrogate marker.

    LENUS (Irish Health Repository)

    Buckley, Patrick G

    2011-03-01

    Loss of chromosome 1p\\/19q in oligodendrogliomas represents a powerful predictor of good prognosis. Expression of internexin (INA), a neuronal specific intermediate filament protein, has recently been proposed as a surrogate marker for 1p\\/19q deletion based on the high degree of correlation between both parameters in oligodendrogliomas. The aim of this study was to assess further the diagnostic utility of INA expression in a set of genetically well-characterized oligodendrogliomas. On the basis of a conservative approach for copy number determination, using both comparative genomic hybridization and fluorescent in situ hybridization, INA expression as a surrogate marker for 1p\\/19q loss had both reduced specificity (80%) and sensitivity (79%) compared with respective values of 86% and 96% reported in the previous report. The histologic interpretation and diagnostic value of INA expression in oligodendrogliomas should therefore be assessed with greater caution when compared with 1p\\/19q DNA copy number analysis. In addition, DNA copy number aberrations of chromosomes 10, 16, and 17 were detected exclusively in 1p\\/19q codeleted samples, suggesting that other regions of the genome may contribute to the 1p\\/19q-deleted tumor phenotype inthese samples.

  16. Genetic isolation of a chromosome 1 region affecting susceptibility to hypertension-induced renal damage in the spontaneously hypertensive rat.

    Science.gov (United States)

    St Lezin, E; Griffin, K A; Picken, M; Churchill, M C; Churchill, P C; Kurtz, T W; Liu, W; Wang, N; Kren, V; Zidek, V; Pravenec, M; Bidani, A K

    1999-08-01

    Linkage studies in the fawn-hooded hypertensive rat have suggested that genes influencing susceptibility to hypertension-associated renal failure may exist on rat chromosome 1q. To investigate this possibility in a widely used model of hypertension, the spontaneously hypertensive rat (SHR), we compared susceptibility to hypertension-induced renal damage between an SHR progenitor strain and an SHR congenic strain that is genetically identical except for a defined region of chromosome 1q. Backcross breeding with selection for the markers D1Mit3 and Igf2 on chromosome 1 was used to create the congenic strain (designated SHR.BN-D1Mit3/Igf2) that carries a 22 cM segment of chromosome 1 transferred from the normotensive Brown Norway rat onto the SHR background. Systolic blood pressure (by radiotelemetry) and urine protein excretion were measured in the SHR progenitor and congenic strains before and after the induction of accelerated hypertension by administration of DOCA-salt. At the same level of DOCA-salt hypertension, the SHR.BN-D1Mit3/Igf2 congenic strain showed significantly greater proteinuria and histologically assessed renal vascular and glomerular injury than the SHR progenitor strain. These findings demonstrate that a gene or genes that influence susceptibility to hypertension-induced renal damage have been trapped in the differential chromosome segment of the SHR.BN-D1Mit3/Igf2 congenic strain. This congenic strain represents an important new model for the fine mapping of gene(s) on chromosome 1 that affect susceptibility to hypertension-induced renal injury in the rat.

  17. Directed isolation and mapping of microsatellites from swine Chromosome 1q telomeric region through microdissection and RH mapping.

    Science.gov (United States)

    Sarker, N; Hawken, R J; Takahashi, S; Alexander, L J; Awata, T; Schook, L B; Yasue, H

    2001-07-01

    Several quantitative trait loci (QTLs) (vertebrate number, birth weight, age at puberty, growth rate, gestation length, and backfat depth) have been independently mapped to the distal region of swine Chromosome (SSC) 1q in several resource populations. In order to improve the map resolution and refine these QTLs more precisely on SSC1q, we have isolated and mapped additional microsatellites (ms), using chromosome microdissection and radiation hybrid (RH) mapping. Five copies of the telomeric region of SSC1q were microdissected from metaphase spreads and pooled. The chromosomal fragment DNA was randomly amplified by using degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR), enriched for ms, and subcloned into a PCR vector. Screening of subsequent clones with ms probes identified 23 unique ms sequences. Fifteen of these (65%) were subjected to radiation hybrid (RH) mapping by using the INRA-University of Minnesota porcine RH panel (IMpRH); and the remaining eight were not suited for the RH mapping. Twelve microsatellites were assigned to SSC1q telomeric region of IMpRH map (LOD >6), and three remain unlinked (LOD pig. In summary, we have used microdissection and radiation hybrid mapping to clone and map 12 new microsatellites to the swine gene map to increase the resolution of SSC1q in the region of known QTLs.

  18. Investigation of QTL regions on Chromosome 17 for genes associated with meat color in the pig.

    Science.gov (United States)

    Fan, B; Glenn, K L; Geiger, B; Mileham, A; Rothschild, M F

    2008-08-01

    Previous studies have uncovered several significant quantitative trait loci (QTL) relevant to meat colour traits mapped at the end of SSC17 in the pig. Furthermore, results released from the porcine genome sequencing project have identified genes underlying the entire QTL regions and can further contribute to mining the region for likely causative genes. Ten protein coding genes or novel transcripts located within the QTL regions were screened for single nucleotide polymorphisms (SNPs). Linkage mapping and association studies were carried out in the ISU Berkshire x Yorkshire (B x Y) pig resource family. The total length of the new SSC17 linkage map was 126.6 cM and additional markers including endothelin 3 (EDN3) and phosphatase and actin regulator 3 (PHACTR3) genes were assigned at positions 119.4 cM and 122.9 cM, respectively. A new QTL peak was noted at approximately 120 cM, close to the EDN3 gene, and for some colour traits QTL exceeded the 5% chromosome-wise significance threshold. The association analyses in the B x Y family showed that the EDN3 BslI and PHACTR3 PstI polymorphisms were strongly associated with the subjective colour score and objective colour reflectance measures in the loin, as well as average drip loss percentage and pH value. The RNPC1 DpnII and CTCFL HpyCH4III polymorphisms were associated with some meat colour traits. No significant association between CBLN4, TFAP2C, and four novel transcripts and meat colour traits were detected. The association analyses conducted in one commercial pig line found that both EDN3 BslI and PHACTR3 PstI polymorphisms were associated with meat colour reflectance traits such as centre loin hue angle and Minolta Lightness score. The present findings suggested that the EDN3 and PHACTR3 genes might have potential effects on meat colour in pigs, and molecular mechanisms of their functions are worth exploring.

  19. Chromosomal Q-heterochromatin regions in native highlanders of Pamir and Tien-Shan and in newcomers.

    Science.gov (United States)

    Ibraimov, A I; Kurmanova, G U; Ginsburg, E Kh; Aksenovich, T I; Aksenrod, E I

    1990-01-01

    The variability of human chromosomal Q-heterochromatin regions (Q-HR) was studied in 385 newcomers well adapted to the extreme environmental conditions of Pamir and Tien-Shan, as well as in 284 representatives of the native population of these regions. Newcomers were found to represent a highly homogeneous group as regards all the quantitative characteristics of Q-HR variability, but at the same time they differed significantly from both native residents and individuals of similar nationality (Russians) living permanently at low altitude. Differences between these three groups in the amount of Q-HRs in their genome are discussed as evidence in favour of the hypothesis of the possible selective value of chromosomal Q-heterochromatin material in human adaptation to extreme environmental high-altitude conditions.

  20. Identification and genetic mapping of a homeobox gene to the 4p16. 1 region of human chromosome 4

    Energy Technology Data Exchange (ETDEWEB)

    Stadler, H.S.; Padanilam, B.J.; Solursh, M. (Univ. of Iowa, Iowa City (United States)); Buetow, K. (Fox Chase Cancer Center, Philadelphia, PA (United States)); Murray, J.C. (Univ. of Iowa Hospitals and Clinics, Iowa City (United States))

    1992-12-01

    A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4P16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3[prime] untranslated region of the H6 cDNA placed this homeobox gene more than 20 centimorgans proximal of the previously mapped HOX7 gene on chromosome 4. Identity comparisons of the H6 Homeodomain with previously reported homeodomains reveal the highest identities to be with the Nk class of homeobox genes in Drosophila melanogaster. 53 refs., 5 figs., 2 tabs.

  1. Identification and genetic mapping of a homeobox gene to the 4p16.1 region of human chromosome 4.

    Science.gov (United States)

    Stadler, H S; Padanilam, B J; Buetow, K; Murray, J C; Solursh, M

    1992-12-01

    A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3' untranslated region of the H6 cDNA placed this homeobox gene more than 20 centimorgans proximal of the previously mapped HOX7 gene on chromosome 4. Identity comparisons of the H6 homeodomain with previously reported homeodomains reveal the highest identities to be with the Nk class of homeobox genes in Drosophila melanogaster.

  2. Sequence variations in the 5' flanking and IVS-II regions of the G gamma- and A gamma-globin genes of beta S chromosomes with five different haplotypes.

    Science.gov (United States)

    Lanclos, K D; Oner, C; Dimovski, A J; Gu, Y C; Huisman, T H

    1991-06-01

    We have amplified and sequenced the 5' flanking and the second intervening sequence (IVS-II) regions of both the G gamma- and A gamma-globin genes of the beta S chromosomes from sickle cell anemia (SS) patients with homozygosities for five different haplotypes. The sequencing data, compared with previously published sequences for the normal chromosomes A and B, show many similarities to chromosome B for haplotypes 19, 20, and 17, while haplotypes 3 and 31 are remarkably similar to chromosome A and also similar to each other. Several unique mutations were found in the 5' flanking regions (G gamma and A gamma) of haplotypes 19 and 20 and in the IVS-II segments of the same genes of haplotypes 19, 20, and 17; the IVS-II of haplotypes 3 and 31 were identical to those of chromosome A. Dot-blot analyses of amplified DNA from additional SS patients with specific probes have confirmed that these mutations are unique for each haplotype. The two general patterns that have been observed among the five haplotypes have most probably arisen by gene conversion events between the A and B type chromosomes in the African population. These patterns correlate with high and low fetal hemoglobin expression, and it is speculated that these and other yet unknown gene conversions may contribute to the variations in hemoglobin F and G gamma levels observed among SS patients. In vitro expression experiments involving the approximately 1.3-kb 5' flanking regions of the G gamma- and A gamma-globin genes of the beta S chromosomes with the five different haplotypes failed to detect differences between the levels of expression, suggesting that the sequence variations observed between these segments of DNA are not the primary cause of the differences in hemoglobin F levels among the SS patients.

  3. Genetic map of the spinocerebellar ataxia type 2 (SCA2) region on chromosome 12

    Energy Technology Data Exchange (ETDEWEB)

    Nechiporuk, A.; Frederick, T.; Pulst, S.M. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others

    1994-09-01

    The autosomal dominant ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive ataxia. At least four gene loci have been identified: SCA1 on chromosome (CHR) 6, SCA2 on CHR12, Machado-Joseph disease on CHR14, and SCA families that are not linked to any of the above loci. In addition, the gene causing dentato-rubro-pallido-luysian atrophy has been identified as an expanded CAG repeat on CHR 12p. As a necessary step in identifying the gene for SCA2, we now identified closer flanking markers. To do this we ordered microsatellite markers in the now identified closer flanking markers. To do this we ordered microsatellite markers in the region and then determined pairwise and multipoint lod scores between the markers and SCA2 in three large pedigrees with SCA. The following order was established with odds > 1,000:1 using six non-SCA pedigrees: D12S101-7.1cM-D12S58-0cM-IGF1-3.6cM-D12S78-1.4cM-D12S317-3.7cM-D12S84-0cM-D12S105-7.2cM-D12S79-7.0cM-PLA2. Using this ordered set of markers we examined linkage to SCA2 in three pedigrees of Italian, Austrian and French-Canadian descent. Pairwise linkage analysis resulted in significant positive lod scores for all markers. The highest pairwise lod score was obtained with D12S84/D12S105 (Z{sub max}=7.98, theta{sub max}=0.05). To further define the location of SCA2, we performed multipoint linkage analysis using the genetic map established above. The highest location score was obtained between D12S317 and D12S84/D12S105. A location of SCA2 between these loci was favored with odds > 100:1. These data likely narrow the SCA2 candidate region to approximately 3.7 cM. The relatively large large number of markers tightly linked to SCA2 will facilitate the assignment of additional SCA pedigrees to CHR12, and will help in the presymptomatic diagnosis of individuals in families with proven linkage to CHR12.

  4. Identification of 2nd chromosome region translocated onto the W chromosome by RFLP with EST-cDNA clones in the Gensei-kouken strains of the mulberry silkworm, Bombyx mori L

    Directory of Open Access Journals (Sweden)

    Sivaramakurup Sreekumar

    2010-01-01

    Full Text Available In silkworms, sex-limited strains are either obtained spontaneously or induced by X-rays or gamma rays. When a fragment of an autosome carrying a dominant allele of those genes responsible for certain characters is translocated onto a W chromosome, the female of the successive generations will express these phenotypic characters and sex discrimination can be facilitated. Gensei-kouken strains are sex-limited strains of silkworms developed by irradiating the pupae with gamma rays, by which a portion of the second chromosome is translocated onto the W chromosome. In these improved strains, the females are yellow-blooded and spin yellow cocoons. By using the EST-cDNA clones mapped on the Z chromosome, we identified the sex according to the polymorphic banding pattern or intensity of the signals. Furthermore, by using the clones on the second chromosome, the region of the second chromosome translocated onto the W chromosome was also defined. In both the A95 and A 96 strains selected for the present study, only the mid-portion of the second chromosome was translocated. The differences in length of the fragments translocated in these strains are discussed.

  5. Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS) in Merino sheep maps to a 1.1-megabase region on ovine chromosome OAR2.

    Science.gov (United States)

    Shariflou, M R; Wade, C M; Kijas, J; McCulloch, R; Windsor, P A; Tammen, I; Nicholas, F W

    2013-04-01

    A genome scan was conducted to map the autosomal recessive lethal disorder brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS) in Poll Merino sheep. The scan involved 10 affected and 27 unaffected animals from a single Poll Merino/Merino sheep flock, which were genotyped with the Illumina Ovine SNP50 BeadChip. Association and homozygosity mapping analyses located the disorder in a region comprising 20 consecutive SNPs spanning 1.1 Mb towards the distal end of chromosome OAR2. All affected animals and none of the unaffected animals were homozygous for the associated haplotype in this region. These results provide the basis for identifying the causative mutation(s) and should enable the development of a DNA test to identify carriers in the Poll Merino sheep population. Understanding the molecular control of BCRHS may provide insight into the fundamental genetic control and regulation of the affected organ systems.

  6. A map of nuclear matrix attachment regions within the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1

    DEFF Research Database (Denmark)

    Shaposhnikov, Sergey A.; Akopov, Sergey B.; Chernov, Igor P.

    2007-01-01

    There is abundant evidence that the DNA in eukaryotic cells is organized into loop domains that represent basic structural and functional units of chromatin packaging. To explore the DNA domain organization of the breast cancer loss-of-heterozygosity region on human chromosome 16q22.1, we have...... identified a significant portion of the scaffold/matrix attachment regions (S/MARs) within this region. Forty independent putative S/MAR elements were assigned within the 16q22.1 locus. More than 90% of these S/MARs are AT rich, with GC contents as low as 27% in 2 cases. Thirty-nine (98%) of the S...

  7. The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization

    Directory of Open Access Journals (Sweden)

    Lo Fang-Yi

    2012-06-01

    Full Text Available Abstract Background Cancer-related genes show racial differences. Therefore, identification and characterization of DNA copy number alteration regions in different racial groups helps to dissect the mechanism of tumorigenesis. Methods Array-comparative genomic hybridization (array-CGH was analyzed for DNA copy number profile in 40 Asian and 20 Caucasian lung cancer patients. Three methods including MetaCore analysis for disease and pathway correlations, concordance analysis between array-CGH database and the expression array database, and literature search for copy number variation genes were performed to select novel lung cancer candidate genes. Four candidate oncogenes were validated for DNA copy number and mRNA and protein expression by quantitative polymerase chain reaction (qPCR, chromogenic in situ hybridization (CISH, reverse transcriptase-qPCR (RT-qPCR, and immunohistochemistry (IHC in more patients. Results We identified 20 chromosomal imbalance regions harboring 459 genes for Caucasian and 17 regions containing 476 genes for Asian lung cancer patients. Seven common chromosomal imbalance regions harboring 117 genes, included gain on 3p13-14, 6p22.1, 9q21.13, 13q14.1, and 17p13.3; and loss on 3p22.2-22.3 and 13q13.3 were found both in Asian and Caucasian patients. Gene validation for four genes including ARHGAP19 (10q24.1 functioning in Rho activity control, FRAT2 (10q24.1 involved in Wnt signaling, PAFAH1B1 (17p13.3 functioning in motility control, and ZNF322A (6p22.1 involved in MAPK signaling was performed using qPCR and RT-qPCR. Mean gene dosage and mRNA expression level of the four candidate genes in tumor tissues were significantly higher than the corresponding normal tissues (PP=0.06. In addition, CISH analysis of patients indicated that copy number amplification indeed occurred for ARHGAP19 and ZNF322A genes in lung cancer patients. IHC analysis of paraffin blocks from Asian Caucasian patients demonstrated that the frequency of

  8. Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus

    Energy Technology Data Exchange (ETDEWEB)

    Nikali, K.; Suomalainen, A.; Koskinen, T.; Peltonen, L. [Univ. of Helsinki (Finland); Terwilliger, J. [Univ. of Oxford (United Kingdom); Weissenbach, J. [Genethon, Evry (France)

    1995-05-01

    Infantile-onset spinocerebellar ataxia (IOSCA) is an autosomal recessively inherited progressive neurological disorder of unknown etiology. This ataxia, identified so far only in the genetically isolated Finnish population, does not share gene locus with any of the previously identified hereditary ataxias, and a random mapping approach was adopted to assign the IOSCA locus. Based on the assumption of one founder mutation, a primary screening of the genome was performed using samples from just four affected individuals in two consanguineous pedigrees. The identification of a shared chromosomal region in these four patients provided the first evidence that the IOSCA gene locus is on chromosome 10q23.3-q24.1, which was confirmed by conventional linkage analysis in the complete family material. Strong linkage disequilibrium observed between IOSCA and the linked markers was utilized to define accurately the critical chromosomal region. The results showed the power of linkage disequilibrium in the locus assignment of diseases with very limited family materials. 30 refs., 3 figs., 2 tabs.

  9. A ninth locus (RP18) for autosomal dominant retinitis pigmentosa maps in the pericentromeric region of chromosome 1.

    Science.gov (United States)

    Xu, S Y; Schwartz, M; Rosenberg, T; Gal, A

    1996-08-01

    We studied a large Danish family of seven generations in which autosomal dominant retinitis pigmentosa (adRP), a heterogeneous genetic form of retinal dystrophy, was segregating. After linkage had been excluded to all known adRP loci on chromosomes 3q, 6p, 7p, 7q, 8q, 17p, 17q and 19q, a genome screening was performed. Positive lod scores suggestive of linkage with values ranging between Z = 1.58-5.36 at theta = 0.04-0.20 were obtained for eight loci on proximal 1p and 1q. Close linkage without recombination and a maximum lod score of 7.22 at theta = 0.00 was found between the adRP locus (RP18) in this family and D1S498 which is on 1q very near the centromere. Analysis of multiply informative meioses suggests that in this family D1S534 and D1S305 flank RP18 in interval 1p13-q23. No linkage has been found to loci from this chromosomal region in six other medium sized adRP families in which the disease locus has been excluded from all known chromosomal regions harbouring an adRP gene or locus suggesting that there is (at least) one further adRP locus to be mapped in the future.

  10. Exclusion of linkage between alcoholism and the MNS blood group region on chromosome 4q in multiplex families

    Energy Technology Data Exchange (ETDEWEB)

    Neiswanger, K.; Kaplan, B.; Hill, S.Y. [Univ. of Pittsburgh School of Medicine, PA (United States)

    1995-02-27

    Polymorphic DNA markers on the long arm of chromosome 4 were used to examine linkage to alcoholism in 20 multiplex pedigrees. Fifteen loci were determined for 124 individuals. Lod scores were calculated assuming both dominant and recessive disease modes of inheritance, utilizing incidence data by age and gender that allow for correction for variable age of onset and frequency of the disorder by gender. Under the assumption that alcoholism is homogeneous in this set of pedigrees, and that a recessive mode with age and gender correction is the most appropriate, the total lod scores for all families combined were uniformly lower than -2.0. This suggests an absence of linkage between the putative alcoholism susceptibility gene and markers in the region of the MNS blood group (4q28-31), a region for which we had previously found suggestive evidence of linkage to alcoholism. The 100 cM span of chromosome 4 studied includes the class I alcohol dehydrogenase (ADH) loci. Using the recessive mode, no evidence for linkage to alcoholism was found for the markers tested, which spanned almost the entire long arm of chromosome 4. Under the dominant mode, no evidence for linkage could be found for several of the markers. 36 refs., 1 fig., 3 tabs.

  11. Tubercular spinal epidural abscess involving the dorsal-lumbar-sacral region without osseous involvement.

    Science.gov (United States)

    Arora, Sumit; Kumar, Ramesh

    2011-07-27

    Musculoskeletal tuberculosis is known for its ability to present in various forms and guises at different sites. Tubercular spinal epidural abscess (SEA) is an uncommon infectious entity. Its presence without associated osseous involvement may be considered an extremely rare scenario. We present a rare case of tubercular SEA in an immune-competent 35-year-old male patient. The patient presented with acute cauda equina syndrome and was shown to have multisegmental SEA extending from D5 to S2 vertebral level without any evidence of vertebral involvement on MRI. The patient made an uneventful recovery following surgical decompression and antitubercular chemotherapy. The diagnosis was confirmed by histopathological demonstration of Mycobacterium tuberculosis in drained pus. Such presentation of tubercular SEA has not been reported previously in the English language based medical literature to the best of our knowledge.

  12. Cloning and deletion mapping of the recF dnaN region of the Escherichia coli chromosome.

    Science.gov (United States)

    Ream, L W; Clark, A J

    1983-09-01

    By cloning a 3.6-kb EcoRI fragment of the Escherichia coli chromosome with pBR322 we located more precisely recF relative to dnaN. By deletion mapping we localized functional recF to a 1.65-kb region of the cloned fragment and allowed rough mapping of the C terminus of dnaN. Cloned recF+, separated from functional flanking genes dnaN and gyrB, complemented chromosomal recF mutations presumably by coding for a cytodiffusible product. The protein encoded by dnaN was observed as a band on a polyacrylamide gel from minicells. Identification of a recF protein was not made.

  13. Investigating Transfer of Large Chromosomal Regions Containing the Pathogenicity Locus Between Clostridium difficile Strains

    NARCIS (Netherlands)

    Brouwer, Mike; Mullany, P.; Allan, E.; Roberts, P.

    2016-01-01

    The genomes of all sequenced Clostridium difficile isolates contain multiple mobile genetic elements. The chromosomally located pathogenicity locus (PaLoc), encoding the cytotoxins TcdA and TcdB, was previously hypothesized to be a mobile genetic element; however, mobility was not demonstrated. Here

  14. Methylation profiling in individuals with uniparental disomy identifies novel differentially methylated regions on chromosome 15.

    NARCIS (Netherlands)

    Sharp, A.J.; Migliavacca, E.; Dupre, Y.; Stathaki, E.; Sailani, M.R.; Baumer, A.; Schinzel, A.; Mackay, D.J.; Robinson, D.O.; Cobellis, G.; Cobellis, L.; Brunner, H.G.; Steiner, B.; Antonarakis, S.E.

    2010-01-01

    The maternal and paternal genomes possess distinct epigenetic marks that distinguish them at imprinted loci. In order to identify imprinted loci, we used a novel method, taking advantage of the fact that uniparental disomy (UPD) provides a system that allows the two parental chromosomes to be studie

  15. Mapping of 5q35 chromosomal rearrangements within a genomically unstable region

    DEFF Research Database (Denmark)

    Buysse, Karen; Crepel, An; Menten, Björn

    2008-01-01

    BACKGROUND: Recent molecular studies of breakpoints of recurrent chromosome rearrangements revealed the role of genomic architecture in their formation. In particular, segmental duplications representing blocks of >1 kb with >90% sequence homology were shown to mediate non-allelic homologous reco...

  16. Exclusion of candidate genes from the chromosome 1q juvenile glaucoma region and mapping of the peripheral cannabis receptor gene (CNR2) to chromosome 1

    Energy Technology Data Exchange (ETDEWEB)

    Sunden, S.L.F.; Nichols, B.E.; Alward, W.L.M. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1994-09-01

    Juvenile onset primary open angle glaucoma has been mapped by linkage to 1q21-q31. Several candidate genes were evaluated in the same family used to identify the primary linkage. Atrionatriuretic peptide receptor A (NPR1) and laminin C1 (LAMC1) have been previously mapped to this region and could putatively play a role in the pathogenesis of glaucoma. A third gene, the peripheral cannabis receptor (CNR2) was not initially mapped in humans but was a candidate because of the relief that cannabis affords some patients with primary open angle glaucoma. Microsatellites associated with NPR1 and LAMC1 revealed multiple recombinations in affected members of this pedigree. CNR2 was shown to be on chromosome 1 by PCR amplification of a 150 bp fragment of the 3{prime} untranslated region in monochromosomal somatic cell hybrids (NIGMS panel No. 2). These primers also revealed a two allele single strand conformation polymorphism which showed multiple recombinants with juvenile onset primary open angle glaucoma in large pedigrees, segregating this disorder. The marker was then mapped to 1p34-p36 by linkage, with the most likely location between liver alkaline phosphatase (ALPL) and alpha-L-1 fucosidase (FUCA1).

  17. Infected Thyroglossal Duct Cyst Involving Submandibular Region: A Case Report

    Directory of Open Access Journals (Sweden)

    Rahul A. Gandhi

    2011-01-01

    Full Text Available Thyroglossal duct cyst presents most frequently in the midline of the neck, either at or just below the level of the hyoid bone. They generally manifest as painless neck swelling, and they move on protrusion of tongue and during swallowing. A case of thyroglossal cyst was reported in the left submandibular region in a 14-year-old girl, above the level of hyoid bone; ultrasound examination favored a cystic lesion which moved in a vertical fashion on swallowing whereas fine needle aspiration cytology report was suggestive of simple cystic lesion of thyroglossal cyst. No lymphoid or malignant cells were present. The cyst was excised completely by surgical procedure under general anesthesia. Histopathological analysis revealed thyroglossal cyst showing columnar and flattened epithelium of cyst with focal aggregate of chronic inflammatory cells supported by fibrocollagenous cyst wall. The clinical, ultrasound, and histopathological findings suggested that the lesion was an infected thyroglossal cyst. There was no evidence of recurrence 6 months after surgery.

  18. Engineered chromosome-based genetic mapping establishes a 3.7-Mb critical genomic region for Down syndrome-associated heart defects in mice

    OpenAIRE

    Liu, Chunhong; Morishima, Masae; Jiang,Xiaoling; Yu, Tao; Meng, Kai; Ray, Debjit; Pao, Annie; Ye, Ping; Parmacek, Michael S.; Yu, Y. Eugene

    2013-01-01

    Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic regions, we found the triplication of the Tiam1-Kcnj6 region on mouse chromosome 16 (Mmu16) resulted in DS-related cardiovascular abnormalities. In this study, we developed two ta...

  19. Mapping of the chromosome 1p36 region surrounding the Charcot-Marie-Tooth disease type 2A locus

    Energy Technology Data Exchange (ETDEWEB)

    Denton, P.; Gere, S.; Wolpert, C. [Duke Univ., Durham, NC (United States)] [and others

    1994-09-01

    Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy. Although CMT2 is clinically indistinguishable from CMT1, the two forms can be differentiated by pathological and neurophysiological methods. We have established one locus, CMT2A on chromosome 1p36, and have established genetic heterogeneity. This locus maps to the region of the deletions associated with neuroblastoma. We have now identified an additional 11 CMT2 families. Three families are linked to chromosome 1p36 while six families are excluded from this region. Another six families are currently under analysis and collection. To date the CMT2A families represent one third of those CMT2 families examined. We have established a microdissection library of the 1p36 region which is currently being characterized for microsatellite repeats and STSs using standard hybridization techniques and a modified degenerate primer method. In addition, new markers (D1S253, D1S450, D1S489, D1S503, GATA27E04, and GATA4H04) placed in this region are being mapped using critical recombinants in the CEPH reference pedigrees. Fluorescent in situ hybridization (FISH) has been used to confirm mapping. A YAC contig is being assembled from the CEPH megabase library using STSs to isolate key YACs which are extended by vectorette end clone and Alu-PCR. These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrates further heterogeneity in the CMT phenotype.

  20. Meiotic abnormalities in metaphase I human spermatocytes from infertile males: frequencies, chromosomes involved, and the relationships with polymorphic karyotype and seminal parameters

    OpenAIRE

    Zaida Sarrate; Francesca Vidal; Joan Blanco

    2014-01-01

    The aim of this study was to look in depth at the relationship between meiotic anomalies and male infertility, such as the determination of the chromosomes involved or the correlation with patient features. For this purpose, a total of 31 testicular tissue samples from individuals consulting for fertility problems were analyzed. Metaphase I cells were evaluated using a sequential methodology combining Leishman stained procedures and multiplex fluorescence in situ hybridization protocols. The ...

  1. Peopling of the North Circumpolar Region--insights from Y chromosome STR and SNP typing of Greenlanders.

    Directory of Open Access Journals (Sweden)

    Jill Katharina Olofsson

    Full Text Available The human population in Greenland is characterized by migration events of Paleo- and Neo-Eskimos, as well as admixture with Europeans. In this study, the Y-chromosomal variation in male Greenlanders was investigated in detail by typing 73 Y-chromosomal single nucleotide polymorphisms (Y-SNPs and 17 Y-chromosomal short tandem repeats (Y-STRs. Approximately 40% of the analyzed Greenlandic Y chromosomes were of European origin (I-M170, R1a-M513 and R1b-M343. Y chromosomes of European origin were mainly found in individuals from the west and south coasts of Greenland, which is in agreement with the historic records of the geographic placements of European settlements in Greenland. Two Inuit Y-chromosomal lineages, Q-M3 (xM19, M194, L663, SA01 and L766 and Q-NWT01 (xM265 were found in 23% and 31% of the male Greenlanders, respectively. The time to the most recent common ancestor (TMRCA of the Q-M3 lineage of the Greenlanders was estimated to be between 4,400 and 10,900 years ago (y. a. using two different methods. This is in agreement with the theory that the North Circumpolar Region was populated via a second expansion of humans in the North American continent. The TMRCA of the Q-NWT01 (xM265 lineage in Greenland was estimated to be between 7,000 and 14,300 y. a. using two different methods, which is older than the previously reported TMRCA of this lineage in other Inuit populations. Our results indicate that Inuit individuals carrying the Q-NWT01 (xM265 lineage may have their origin in the northeastern parts of North America and could be descendants of the Dorset culture. This in turn points to the possibility that the current Inuit population in Greenland is comprised of individuals of both Thule and Dorset descent.

  2. Genetic and physical mapping of two centromere-proximal regions of chromosome IV in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Aleksenko, Alexei Y.; Nielsen, Michael Lynge; Clutterbuck, A.J.

    2001-01-01

    The centromere-proximal portion of the chromosome was mapped physically using overlapping clones of a cosmid genomic library. Two contiguous segments of a physical map, based on restriction mapping of cosmid clones, were generated, together covering more than 0.4 Mb DNA. A reverse genetic mapping...... approach was used to establish a correlation between physical and genetic maps; i,e., marker genes were integrated into physically mapped segments and subsequently mapped by mitotic and meiotic recombination. The resulting data, together with additional classical genetic mapping, lead to a substantial...... revision of the genetic map of the chromosome, including the position of the centromere, Comparison of physical and genetic maps indicates that meiotic recombination is low in subcentromeric DNA, its frequency being reduced from 1 crossover per 0.8 Mb to approximately 1 crossover per 5 Mb per meiosis...

  3. Polymorphism analysis of microsatellites and construction of linkage map in part regions of four chromosomes in chicken

    Institute of Scientific and Technical Information of China (English)

    WANG Shouzhi; LI Hui; LI Ning; GAO Yu; DU Zhiqiang; GU Zhiliang; WANG Qigui; LI Zhihui; WANG Ying

    2007-01-01

    Based on chicken' consensus map issued in 2000, 17 microsatellites near 4 candidate genes such as IGF2, OBR, GDFS and APOA1 in 4 chromosomes (chromosome 5, 7, 8 and 24) were chosen for polymorphism analysis and construction of linkage map. Combining the technique of PCR and the fluorescent semi-automated detection, genome scanning was performed for 440 chickens, which was derived from China Agricultural University chicken resource families within three generations. The individuals of this resource families were genotyped. The results showed that the number of alleles ranged from 4 to 14; heterozygosity (H) of markers was between 0.3116 and 0.9148. Polymorphic information content (PIC) varied from 0.2672 to 0.8679. Microsatellites along with above-mentioned 4 candidate genes doing as general markers were used to construct linkage map. The spans of 4 linkage maps constructed in the part region of chromosome 5, 7, 8 and 24 were 263.5, 79.9, 206.2 and 104.2 cM, respectively. The order of markers was consistent with that of counterpart of reported consensus map. However, The spans of linkage map were larger than that of consensus map. The constructed linkage maps laid the foundation for mapping quantitative trait loci (QTL) responsible for economically important traits in chicken.

  4. An apparently de novo translocation in a neonate involving chromosomes 3 and 19 [t(3:19)(p21;q13.1)

    Energy Technology Data Exchange (ETDEWEB)

    Shah, H.O.; Buttice, L.S.; Chester, M. [Nassau County Medical Center, East Meadow, NY (United States)] [and others

    1994-09-01

    A 7 1/2-week-old infant female was referred for cytogenetic evaluation after she developed a left inguinal hernia containing a gonadal mass. She had been born to a 25-year-old mother after approximately 31 weeks gestation. This was the couple`s first pregnancy. She was small for gestational age. Her weight was 835 g, length was 32 cm, head circumference was 26 cm at birth. She developed hypothyroidism requiring synthroid. There were no other obvious dysmorphisms. The cytogenetic findings with G-banding revealed an apparently-balanced translocation involving chromosomes 3 and 19. The patient`s karyotype revealed 46,XX,t(3;19)(q21;q13.1). Parental chromosomes were found to be normal. Because of the increased risk for developmental and other congenital problems in an individual with a {open_quotes}de novo translocation{close_quotes} (even when the rearrangement appears balanced), this infant is being followed regularly. Evaluation at 5 months of age revealed a small but thriving female infant who is alert and developmentally appropriate. She is still receiving synthroid. We are in the process of analyzing this case further using chromosome paint probes for chromosomes 3 and 19 to identify the break points more precisely. This would allow us to assess with greater accuracy if this is a {open_quotes}balanced{close_quotes} translocation.

  5. Three-way complex variant translocation involving short arm chromosome (1;9;22)(p36;q34;q11) in a chronic myeloid leukemia patient

    Science.gov (United States)

    ASIF, MUHAMMAD; HUSSAIN, ABRAR; MALIK, ARIF; RASOOL, MAHMOOD

    2015-01-01

    Chronic myeloid leukemia (CML) is a disease of the clonal hematopoietic stem cells caused by a balanced translocation between the long arms of chromosomes 9 and 22. Overall, 90–95% of CML patients present with a Philadelphia (Ph) chromosome t(9;22)(q34;q11) translocation and in addition, variant complex translocations, involving a third chromosome, are observed in 5–8% of CML patients. Cytogenic testing using bone marrow sample was performed and the FISH test was used for the detection of BCR-ABL fusion gene and complete blood analysis of CML patient was also performed. Results of hematological analysis showed the induced values of white blood cells (168,5000/mm3) and platelets (300,000/mm3) and FISH analysis test showed that 98% cells were positive for BCR/ABL gene translocation. The present study describes a three-way (1;9;22)(p36;q34;q11) Ph chromosome translocation in a 24-year-old female with CML. The patient, who was in the chronic phase of the disease, was treated with daily dose of 400 mg/dl with imatinib mesylateand was monitored constantly at various intervals over a 6-month period. Many studies reported that certain CML patents with variant translocation responded poorly to imatinib. In the current case report, the CML patient exhibited a suboptimal response to imatinib, denoting a poor prognosis. PMID:26622740

  6. Meiotic abnormalities in metaphase I human spermatocytes from infertile males: frequencies, chromosomes involved, and the relationships with polymorphic karyotype and seminal parameters

    Directory of Open Access Journals (Sweden)

    Zaida Sarrate

    2014-12-01

    Full Text Available The aim of this study was to look in depth at the relationship between meiotic anomalies and male infertility, such as the determination of the chromosomes involved or the correlation with patient features. For this purpose, a total of 31 testicular tissue samples from individuals consulting for fertility problems were analyzed. Metaphase I cells were evaluated using a sequential methodology combining Leishman stained procedures and multiplex fluorescence in situ hybridization protocols. The number of chromosomal units and chiasmata count per bivalent were established and a hierarchical cluster analysis of the individuals was performed. The relationship of the seminogram and the karyotype over recombination were evaluated using Poisson regression models. Results obtained in this study show a significant percentage of infertile individuals with altered meiotic behavior, mostly specified as a reduction in chiasmata count in medium and large chromosomes, the presence of univalents, and the observation of tetraploid metaphases. Moreover, the number and the type of anomalies were found to be different between cells of the same individual, suggesting the coexistence of cell lines with normal meiotic behavior and cell lines with abnormalities. In addition, chromosomal abnormalities in metaphase I are significantly associated with oligozoospermia and/or polymorphic karyotype variants.

  7. Meiotic abnormalities in metaphase I human spermatocytes from infertile males: frequencies, chromosomes involved, and the relationships with polymorphic karyotype and seminal parameters.

    Science.gov (United States)

    Sarrate, Zaida; Vidal, Francesca; Blanco, Joan

    2014-01-01

    The aim of this study was to look in depth at the relationship between meiotic anomalies and male infertility, such as the determination of the chromosomes involved or the correlation with patient features. For this purpose, a total of 31 testicular tissue samples from individuals consulting for fertility problems were analyzed. Metaphase I cells were evaluated using a sequential methodology combining Leishman stained procedures and multiplex fluorescence in situ hybridization protocols. The number of chromosomal units and chiasmata count per bivalent were established and a hierarchical cluster analysis of the individuals was performed. The relationship of the seminogram and the karyotype over recombination were evaluated using Poisson regression models. Results obtained in this study show a significant percentage of infertile individuals with altered meiotic behavior, mostly specified as a reduction in chiasmata count in medium and large chromosomes, the presence of univalents, and the observation of tetraploid metaphases. Moreover, the number and the type of anomalies were found to be different between cells of the same individual, suggesting the coexistence of cell lines with normal meiotic behavior and cell lines with abnormalities. In addition, chromosomal abnormalities in metaphase I are significantly associated with oligozoospermia and/or polymorphic karyotype variants.

  8. Identification of a high frequency of chromosomal rearrangements in the centromeric regions of prostate cancer patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation,inversion and mosaic in prostate cancer patients of Tamilnadu, Southern India. Totally 45 blood samples were collected from various hospitals in Tamilnadu, Southern India. Equal numbers of normal healthy subjects were chosen after signing a consent form. Volunteers provided blood samples (5 ml) to establish leukocyte cultures. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by spectral karyotyping (SKY) technique. In the present investigation, major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. Results showed frequent CA in chromosomes 1, 3, 5, 6, 7, 9, 13, 16, 18 and X. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P<0.05). In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the centromere in prostate cancer tumorigenesis. Identification of chromosome alterations may be helpful in understanding the molecular basis of the disease in better manner.

  9. 4p16.3 microdeletions and microduplications detected by chromosomal microarray analysis: New insights into mechanisms and critical regions.

    Science.gov (United States)

    Bi, Weimin; Cheung, Sau-Wai; Breman, Amy M; Bacino, Carlos A

    2016-10-01

    Deletions in the 4p16.3 region cause Wolf-Hirschhorn syndrome, a well known contiguous microdeletion syndrome with the critical region for common phenotype mapped in WHSCR2. Recently, duplications in 4p16.3 were reported in three patients with developmental delay and dysmorphic features. Through chromosomal microarray analysis, we identified 156 patients with a deletion (n = 109) or duplication (n = 47) in 4p16.3 out of approximately 60,000 patients analyzed by Baylor Miraca Genetics Laboratories. Seventy-five of the postnatally detected deletions encompassed the entire critical region, 32 (43%) of which were associated with other chromosome rearrangements, including six patients (8%) that had a duplication adjacent to the terminal deletion. Our data indicate that Wolf-Hirschhorn syndrome deletions with an adjacent duplication occur at a higher frequency than previously appreciated. Pure deletions (n = 14) or duplications (n = 15) without other copy number changes distal to or inside the WHSCR2 were identified for mapping of critical regions. Our data suggest that deletion of the segment from 0.6 to 0.9 Mb from the terminus of 4p causes a seizure phenotype and duplications of a region distal to the previously defined smallest region of overlap for 4p16.3 microduplication syndrome are associated with neurodevelopmental problems. We detected seven Wolf-Hirschhorn syndrome deletions and one 4p16.3 duplication prenatally; all of the seven are either >8 Mb in size and/or associated with large duplications. In conclusion, our study provides deeper insight into the molecular mechanisms, the critical regions and effective prenatal diagnosis for 4p16.3 deletions/ duplications. © 2016 Wiley Periodicals, Inc.

  10. Postzygotic isolation involves strong mitochondrial and sex-specific effects in Tigriopus californicus, a species lacking heteromorphic sex chromosomes.

    Science.gov (United States)

    Foley, B R; Rose, C G; Rundle, D E; Leong, W; Edmands, S

    2013-11-01

    Detailed studies of the genetics of speciation have focused on a few model systems, particularly Drosophila. The copepod Tigriopus californicus offers an alternative that differs from standard animal models in that it lacks heteromorphic chromosomes (instead, sex determination is polygenic) and has reduced opportunities for sexual conflict, because females mate only once. Quantitative trait loci (QTL) mapping was conducted on reciprocal F2 hybrids between two strongly differentiated populations, using a saturated linkage map spanning all 12 autosomes and the mitochondrion. By comparing sexes, a possible sex ratio distorter was found but no sex chromosomes. Although studies of standard models often find an excess of hybrid male sterility factors, we found no QTL for sterility and multiple QTL for hybrid viability (indicated by non-Mendelian adult ratios) and other characters. Viability problems were found to be stronger in males, but the usual explanations for weaker hybrid males (sex chromosomes, sensitivity of spermatogenesis, sexual selection) cannot fully account for these male viability problems. Instead, higher metabolic rates may amplify deleterious effects in males. Although many studies of standard speciation models find the strongest genetic incompatibilities to be nuclear-nuclear (specifically X chromosome-autosome), we found the strongest deleterious interaction in this system was mito-nuclear. Consistent with the snowball theory of incompatibility accumulation, we found that trigenic interactions in this highly divergent cross were substantially more frequent (>6×) than digenic interactions. This alternative system thus allows important comparisons to studies of the genetics of reproductive isolation in more standard model systems.

  11. Analysis of plant meiotic chromosomes by chromosome painting.

    Science.gov (United States)

    Lysak, Martin A; Mandáková, Terezie

    2013-01-01

    Chromosome painting (CP) refers to visualization of large chromosome regions, entire chromosome arms, or entire chromosomes via fluorescence in situ hybridization (FISH). For CP in plants, contigs of chromosome-specific bacterial artificial chromosomes (BAC) from the target species or from a closely related species (comparative chromosome painting, CCP) are typically applied as painting probes. Extended pachytene chromosomes provide the highest resolution of CP in plants. CP enables identification and tracing of particular chromosome regions and/or entire chromosomes throughout all meiotic stages as well as corresponding chromosome territories in premeiotic interphase nuclei. Meiotic pairing and structural chromosome rearrangements (typically inversions and translocations) can be identified by CP. Here, we describe step-by-step protocols of CP and CCP in plant species including chromosome preparation, BAC DNA labeling, and multicolor FISH.

  12. Use of an intron length polymorphism to localize the tropoelastin gene to mouse Chromosome 5 in a region of linkage conservation with human Chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Wydner, K.S.; Passmore, H.C. [Rutgers Univ., Piscataway, NJ (United States); Sechler, J.L.; Boyd, C.D. [UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ (United States)

    1994-09-01

    The complete coding sequence for mouse tropoelastin was obtained from overlapping reverse transcriptase polymerase chain reaction (PCR) amplimers. These cDNA fragments were derived from mouse tropoelastin mRNA using PCR oligomers complementary to conserved domains within rat tropoelastin mRNA. A comparison of coding domains of mouse and rat tropoelastin mRNA revealed a greater than 93% homology at the nucleotide level and over 96% similarity in the predicted amino acid sequence. PCR primers complementary to regions of the mouse tropoelastin mRNA were used to define a novel intron length polymorphism (ILP) within intron 8 of the mouse tropoelastin gene (Eln). This ILP proved to be informative in an intraspecific backcross in which genomic DNA samples from 75 backcross mice were used to map the tropoelastin gene to a position in the distal half of mouse chromosome 5. The linkage and genetic distances between Eln and the closest molecular markers used in this study are centromere-D5Mit95, D5Mit96-6.7 cM-Gus, Eln-4.0 cM-Zp3-telomere.

  13. Identification and genetic mapping of a homeobox gene to the 4p16.1 region of human chromosome 4.

    OpenAIRE

    Stadler, H S; Padanilam, B J; Buetow, K; Murray, J.C.; Solursh, M

    1992-01-01

    A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 region by using somatic cell hybrids containing specific deletions of human chromosome 4. Linkage data from a single-stranded conformational polymorphism derived from the 3' untra...

  14. Analysis of two novel cDNAs from the Smith-Magenis syndrome region on chromosome 17

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Z.Y.; Lee, C.C.; Jiralerspong, S. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital anomaly/mental retardation syndrome associated with deletion of chromosome 17p11.2. To date, only one gene encoding snRNA U3 has been mapped to this region. Here we report the identification of two novel genes, designated 463 and B9, which have been mapped to the SMS region. A full-length cDNA corresponding to each of these genes has been cloned and sequenced. Deletion analysis has been conducted on somatic cell hybrids retaining the del(17)(p11.2) chromosome from each of 15 SMS patients by PCR of sequence tagged sites for the cDNAs and confirmed by Southern analysis. The gene 463 is deleted in 15/15 patients analyzed to date, whereas the gene B9 is deleted in 10/15 of the patients analyzed. Fluorescence in situ hybridization is used to analyze additional SMS patients for hemizygosity at these loci. A physical map of the region is being constructed to determine the relative location of these cDNAs within 17p11.2. Our studies to date, thus, suggest that although both genes 463 and B9 are located within 17p11.2, gene 463 is more likely to be associated with SMS. Complete and exhaustive definition of the critical interval is required to demonstrate the role and importance of gene 463 in SMS.

  15. Mapping autonomously replicating sequence elements in a 73-kb region of chromosome II of the fission yeast, Schizosaccharomyces pombe

    Indian Academy of Sciences (India)

    Vinay Kumar Srivastava; Dharani Dhar Dubey

    2007-08-01

    Autonomously replicating sequence (ARS) elements are the genetic determinants of replication origin function in yeasts. They can be easily identified as the plasmids containing them transform yeast cells at a high frequency. As the first step towards identifying all potential replication origins in a 73-kb region of the long arm of fission yeast chromosome II, we have mapped five new ARS elements using systematic subcloning and transformation assay. 2D analysis of one of the ARS plasmids that showed highest transformation frequency localized the replication origin activity within the cloned genomic DNA. All the new ARS elements are localized in two clusters in centromere proximal 40 kb of the region. The presence of at least six ARS elements, including the previously reported ars727, is suggestive of a higher origin density in this region than that predicted earlier using a computer based search.

  16. Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region

    DEFF Research Database (Denmark)

    Lusk, Christine M; Dyson, Greg; Clark, Andrew G;

    2014-01-01

    Markers of the chromosome 9p21 region are regarded as the strongest and most reliably significant genome-wide association study (GWAS) signals for Coronary heart disease (CHD) risk; this was recently confirmed by the CARDIoGRAMplusC4D Consortium meta-analysis. However, while these associations...... genotypes in the 9p21 region were strongest in a sub-group of hypertensives. We subsequently validated the effect of the region in an independent sample from the Copenhagen City Heart Study. Our study suggests that marker SNPs identified as predictors of CHD risk in large population based GWAS may have...... their greatest utility in explaining risk of disease in particular sub-groups characterized by biological and environmental effects measured by the traditional CHD risk factors....

  17. Regional assignment of the human uroporphyrinogen III synthase (UROS) gene to chromosome 10q25.2----q26.3.

    Science.gov (United States)

    Astrin, K H; Warner, C A; Yoo, H W; Goodfellow, P J; Tsai, S F; Desnick, R J

    1991-05-01

    Uroporphyrinogen III synthase [UROS; hydroxymethylbilane hydro-lyase (cyclizing), EC 4.2.1.75] is the fourth enzyme in the human heme biosynthetic pathway. The recent isolation of the cDNA encoding human UROS facilitated its chromosomal localization. Human UROS sequences were specifically amplified by the polymerase chain reaction (PCR) from genomic DNA of two independent panels of human-rodent somatic cell hybrids. There was 100% concordance for the presence of the human UROS PCR product and human chromosome 10. For each of the other chromosomes, there was 19%-53% discordance with human UROS. The chromosomal assignment was confirmed by Southern hybridization analysis of DNA from somatic cell hybrids with the full-length UROS cDNA. Using human-rodent hybrids containing different portions of human chromosome 10, we assigned the UROS gene to the region 10q25.2----q26.3.

  18. A 1.6-Mb P1-based physical map of the Down syndrome region on chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Ohira, Miki; Suzuki, Kazunobu [National Cancer Center Research Institute, Tokyo (Japan)]|[Kazusa DNA Research Institute, Chiba (Japan); Ichikawa, Hitoshi [National Cancer Center Research Institute, Tokyo (Japan)] [and others

    1996-04-01

    The Down Syndrome (DS) region on chromosome 21, which is responsible for the main features of DS such as characteristic facial features, a congenital heart defect, and mental retardation, has been defined by molecular analysis of DS patients with partial trisomy 21. The 2.5-Mb region around the marker D21S55 between D21S17 and ERG in 21q22 is thought to be important, although contributions of other regions cannot be excluded. In this region, we focused on a 1.6-Mb region between a NotI site, LA68 (D21S396, which is mapped distal to D21S17) and ERG, because analysis of a Japanese DS family with partial trisomy 21 revealed that the proximal border of its triplicated region was distal to LA68. We constructed P1 contigs with 46 P1 clones covering more than 95% of the 1.6-Mb region. A high-resolution restriction map using BamHI was also constructed for more details analysis. Our P1 contig map supplements other physical maps previously reported and provides useful materials for further analysis including isolation and sequencing of the DS region. 31 refs., 7 figs., 1 tab.

  19. A Meiotic Drive Element in the Maize Pathogen Fusarium verticillioides Is Located Within a 102 kb Region of Chromosome V.

    Science.gov (United States)

    Pyle, Jay; Patel, Tejas; Merrill, Brianna; Nsokoshi, Chabu; McCall, Morgan; Proctor, Robert H; Brown, Daren W; Hammond, Thomas M

    2016-08-09

    Fusarium verticillioides is an agriculturally important fungus because of its association with maize and its propensity to contaminate grain with toxic compounds. Some isolates of the fungus harbor a meiotic drive element known as Spore killer (Sk(K)) that causes nearly all surviving meiotic progeny from an Sk(K) × Spore killer-susceptible (Sk(S)) cross to inherit the Sk(K) allele. Sk(K) has been mapped to chromosome V but the genetic element responsible for meiotic drive has yet to be identified. In this study, we used cleaved amplified polymorphic sequence markers to genotype individual progeny from an Sk(K) × Sk(S) mapping population. We also sequenced the genomes of three progeny from the mapping population to determine their single nucleotide polymorphisms. These techniques allowed us to refine the location of Sk(K) to a contiguous 102 kb interval of chromosome V, herein referred to as the Sk region. Relative to Sk(S) genotypes, Sk(K) genotypes have one extra gene within this region for a total of 42 genes. The additional gene in Sk(K) genotypes, herein named SKC1 for Spore Killer Candidate 1, is the most highly expressed gene from the Sk region during early stages of sexual development. The Sk region also has three hyper-variable regions, the longest of which includes SKC1 The possibility that SKC1, or another gene from the Sk region, is an essential component of meiotic drive and spore killing is discussed.

  20. Evaluation of chromosome 5 aberrations in complex karyotypes of patients with myeloid disorders reveals their contribution to dicentric and tricentric chromosomes, resulting in the loss of critical 5q regions.

    Science.gov (United States)

    Herry, Angèle; Douet-Guilbert, Nathalie; Morel, Frédéric; Le Bris, Marie-Josée; Morice, Patrick; Abgrall, Jean François; Berthou, Christian; De Braekeleer, Marc

    2007-06-01

    Dicentric chromosomes have often been observed in complex karyotypes in previously reported studies of therapy-related myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Fluorescence in situ hybridization (FISH) has now made the characterization of these rearrangements much easier. Dicentric and tricentric chromosomes were identified in 21 patients (9 MDS and 12 AML) among the 133 consecutive MDS/AML patients (17%) who had a structural or numerical aberration of chromosome 5 using conventional cytogenetic analysis. One third (7/21) of the patients had received alkylating drugs for a previously diagnosed cancer or chronic myeloproliferative disease. Loss of 5q material was identified in all 21 patients. One copy of the EGR1 (5q31) or the CSF1R (5q33 approximately q34) genes was lost in 20 of the 21 patients. Dicentric and tricentric chromosomes involving chromosome 5 are frequently observed in complex karyotypes among patients with de novo or therapy-related MDS/AML. They lead to deletions of various parts of the long arm of chromosome 5.

  1. Epilepsy phenotype associated with a chromosome 2q24.3 deletion involving SCN1A: Migrating partial seizures of infancy or atypical Dravet syndrome?

    Science.gov (United States)

    Lim, Byung Chan; Hwang, Hee; Kim, Hunmin; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Yum, Mi-Sun; Ko, Tae-Sung

    2015-01-01

    The deletion of a sodium channel gene cluster located on chromosome 2q24.3 is associated with variable epilepsy phenotypes, including Dravet syndrome and migrating partial seizures of infancy. Although SCN1A is considered as the major contributor to the epilepsy phenotype, the role of other sodium channel genes that map within this cluster has not been delineated. We presented five new cases with a chromosome 2q24.3 deletion involving SCN1A and investigated their epilepsy phenotype in relation to the extent of the deletion. Three cases with deletion of the whole sodium channel gene cluster (SCN3A, SCN2A, SCN1A, SCN9A, and SCN7A) exhibited a complex epilepsy phenotype that was atypical for Dravet syndrome and suggestive of migrating partial seizures of infancy: early seizure onset (before 2 months of age), severe developmental delay from seizure onset, multifocal interictal spikes, polymorphous focal seizures, and acquired microcephaly. Two cases with partial deletion of SCN1A and SCN9A and whole SCN1A deletion had an epilepsy phenotype of Dravet syndrome. A literature review of cases with chromosome 2q24.3 deletion revealed that, in most Dravet syndrome cases, it does not involve SCN2A and SCN3A, whereas a complex epilepsy phenotype that is shared with migrating partial seizures of infancy was associated with cases of deletion of the whole sodium channel gene cluster.

  2. Localization of the human indoleamine 2,3-dioxygenase (IDO) gene to the pericentromeric region of human chromosome 8

    Energy Technology Data Exchange (ETDEWEB)

    Burkin, D.J.; Jones, C. (Eleanor Roosevelt Institute for Cancer Research, Denver, CO (United States)); Kimbro, K.S.; Taylor, M.W. (Indiana Univ., Bloomington, IN (United States)); Barr, B.L.; Gupta, S.L. (Hipple Cancer Research Center, Dayton, OH (United States))

    1993-07-01

    Indoleamine 2,3-dioxygenase (IDO) is the first enzyme in the catabolic pathway for tryptophan. This extrahepatic enzyme differs from the hepatic enzyme, tryptophan 2,3-dioxygenase (TDO), in molecular as well as enzymatic characteristics, although both enzymes catalyze the same reaction: cleavage of tryptophan into N-formylkynurenine. The induction of IDO by IFN-[gamma] plays a role in the antigrowth effect of IFN-[gamma] in cell cultures and in the inhibition of intracellular pathogens, e.g., Toxoplasma gondii and Chlamydia psittaci. Tryptophan is also the precursor for the synthesis of serotonin, and reduced levels of tryptophan and serotonin found in AIDS patients have been correlated with the presence of IFN-[gamma] and consequent elevation of IDO activity. The IDO enzyme has been purified and characterized, and its cDNA and genomic DNA clones have been isolated and analyzed. DNA from hybrid cells containing fragments of human chromosome 8 was used to determine the regional localization of the IDO gene on chromosome 8. The hybrids R30-5B and R30-2A contain 8p11 [yields] qter and 8q13 [yields] qter, respectively. Hybrid 229-3A contains the 8pter [yields] q11. The hybrid R30-2A was negative for the IDO gene, whereas R30-5B and 229-3A were positive as analyzed by PCR and verified by Southern blotting. Only the region close to the centromere is shared by R30-5B and 229-3A hybrids. The results indicate that the IDO gene is located on chromosome 8p11 [yields] q11.

  3. Identification of Chromosome Abnormalities in Subtelomeric Regions by Microarray Analysis: A Study of 5,380 Cases

    Science.gov (United States)

    Shao, Lina; Shaw, Chad A.; Lu, Xin-Yan; Sahoo, Trilochan; Bacino, Carlos A.; Lalani, Seema R.; Stankiewicz, Pawel; Yatsenko, Svetlana A.; Li, Yinfeng; Neill, Sarah; Pursley, Amber N.; Chinault, A. Craig; Patel, Ankita; Beaudet, Arthur L.; Lupski, James R.; Cheung, Sau W.

    2009-01-01

    Subtelomeric imbalances are a significant cause of congenital disorders. Screening for these abnormalities has traditionally utilized GTG-banding analysis, fluorescence in situ hybridization (FISH) assays, and multiplex ligation-dependent probe amplification. Microarray-based comparative genomic hybridization (array-CGH) is a relatively new technology that can identify microscopic and submicroscopic chromosomal imbalances. It has been proposed that an array with extended coverage at subtelomeric regions could characterize subtelomeric aberrations more efficiently in a single experiment. The targeted arrays for chromosome microarray analysis (CMA), developed by Baylor College of Medicine, have on average 12 BAC/PAC clones covering 10 Mb of each of the 41 subtelomeric regions. We screened 5,380 consecutive clinical patients using CMA. The most common reasons for referral included developmental delay (DD), and/or mental retardation (MR), dysmorphic features (DF), multiple congenital anomalies (MCA), seizure disorders (SD), and autistic, or other behavioral abnormalities. We found pathogenic rearrangements at subtelomeric regions in 236 patients (4.4%). Among these patients, 103 had a deletion, 58 had a duplication, 44 had an unbalanced translocation, and 31 had a complex rearrangement. The detection rates varied among patients with a normal karyotype analysis (2.98%), with an abnormal karyotype analysis (43.4%), and with an unavailable or no karyotype analysis (3.16%). Six patients out of 278 with a prior normal subtelomere-FISH analysis showed an abnormality including an interstitial deletion, two terminal deletions, two interstitial duplications, and a terminal duplication. In conclusion, genomic imbalances at subtelomeric regions contribute significantly to congenital disorders. Targeted array-CGH with extended coverage (up to 10 Mb) of subtelomeric regions will enhance the detection of subtelomeric imbalances, especially for submicroscopic imbalances. PMID

  4. Nephropathic cystinosis (CTNS-LSB): construction of a YAC contig comprising the refined critical region on chromosome 17p13.

    Science.gov (United States)

    Peters, U; Senger, G; Rählmann, M; Du Chesne, I; Stec, I; Köhler, M R; Weissenbach, J; Leal, S M; Koch, H G; Deufel, T; Harms, E

    1997-01-01

    A yeast artificial chromosome (YAC) contig was constructed encompassing the entire region on chromosome 17p13 where the autosomal recessive disorder infantile nephropathic cystinosis (MIM 21980, CTNS-LSB) has been genetically mapped. It comprises seven clones ordered by their content of a series of six sequence-tagged sites (STSs). Fluorescence in situ hybridisation (FISH) revealed two chimaeric clones. The order of four polymorphic STSs mapped with the contig was consistent with that of the known genetic map with the exception of markers D17S1583 (AFMb307zg5) and D17S1798 (AFMa202xf5) where a telomeric location of D17S1583 was inferred from the contig; two non-polymorphic STSs were localised within the marker frame-work. From the analysis of recombination events in an unaffected individual as defined by leucocyte cystine levels we support the high-resolution mapping of this region to a small genetic interval and show that it is entirely represented on a single, non-chimaeric YAC clone in the contig.

  5. Induction of micronuclei, hyperdiploidy and chromosomal breakage affecting the centric/pericentric regions of chromosomes 1 and 9 in human amniotic fluid cells after treatment with asbestos and ceramic fibers.

    Science.gov (United States)

    Dopp, E; Schuler, M; Schiffmann, D; Eastmond, D A

    1997-06-09

    This article describes the induction of micronuclei, hyperdiploidy and chromosome breakage in human amniotic cells in vitro by amosite, chrysotile and crocidolite asbestos, and ceramic fibers. The response of human (amniotic fluid cells) and rodent (Syrian hamster embryo fibroblasts, SHE) cells to fiber treatment was compared using the micronucleus assay. The data of the rodent studies were taken from a previous investigation (Dopp, E. et al. (1995) Environ. Health Perspect., 103, 268-271). All types of mineral fibers caused a significant increase of micronucleated cells. The kinetochore analysis revealed that all three types of asbestos and ceramic fibers yielded similar effects. Approximately 50% of the induced micronuclei were kinetochore-negative indicating formation through clastogenic events. Human amniotic cells were much less susceptible than SHE cells to the induction of micronuclei by mineral fibers. This again demonstrates that SHE cells are more susceptible to chromosomal changes than human amniotic fluid cells. The application of fluorescence in situ hybridization (FISH) with tandem DNA probes yielded more detailed information about specific structural chromosome aberrations in the 1 (cen-q12) and 9 (cen-q12) regions and about abnormal numbers of chromosomes in interphase human amniotic fluid cells. Using this FISH approach we found a statistically significant increase of chromosomal breakage in the pericentric heterochromatin regions of chromosomes 1 and 9 in interphase human amniotic cells after exposure to asbestos and ceramic fibers compared to control cells. The number of hyperdiploid cells was also significantly increased. Our results show that asbestos fibers as well as ceramic fibers are inducers of structural and numerical chromosomal aberrations in human amniotic fluid cells.

  6. A small XY chromosomal region explains sex determination in wild dioecious V. vinifera and the reversal to hermaphroditism in domesticated grapevines

    OpenAIRE

    Picq, Sandrine; Santoni, Sylvain; Lacombe, Thierry; Latreille, Muriel; Weber, Audrey; Ardisson, Morgane; Ivorra, Sarah; Maghradze, David; Arroyo-Garcia, Rosa; Chatelet, Philippe; This, Patrice; Terral, Jean-Fédéric; Bacilieri, Roberto

    2014-01-01

    Publis014-agap-029; Background In Vitis vinifera L., domestication induced a dramatic change in flower morphology: the wild sylvestris subspecies is dioecious while hermaphroditism is largely predominant in the domesticated subsp. V. v. vinifera. The characterisation of polymorphisms in genes underlying the sex-determining chromosomal region may help clarify the history of domestication in grapevine and the evolution of sex chromosomes in plants. In the genus Vitis, sex determination is putat...

  7. Microhomology-mediated microduplication in the y chromosomal azoospermia factor a region in a male with mild asthenozoospermia.

    Science.gov (United States)

    Katsumi, Momori; Ishikawa, Hiromichi; Tanaka, Yoko; Saito, Kazuki; Kobori, Yoshitomo; Okada, Hiroshi; Saito, Hidekazu; Nakabayashi, Kazuhiko; Matsubara, Yoichi; Ogata, Tsutomu; Fukami, Maki; Miyado, Mami

    2014-01-01

    Y chromosomal azoospermia factor (AZF) regions AZFa, AZFb and AZFc represent hotspots for copy number variations (CNVs) in the human genome; yet the number of reports of AZFa-linked duplications remains limited. Nonallelic homologous recombination has been proposed as the underlying mechanism of CNVs in AZF regions. In this study, we identified a hitherto unreported microduplication in the AZFa region in a Japanese male individual. The 629,812-bp duplication contained 22 of 46 exons of USP9Y, encoding the putative fine tuner of spermatogenesis, together with all exons of 3 other genes/pseudogenes. The breakpoints of the duplication resided in the DNA/TcMar-Tigger repeat and nonrepeat sequences, respectively, and were associated with a 2-bp microhomology, but not with short nucleotide stretches. The breakpoint-flanking regions were not enriched with GC content, palindromes, or noncanonical DNA structures. Semen analysis of the individual revealed a normal sperm concentration and mildly reduced sperm motility. The paternal DNA sample of the individual was not available for genetic analysis. The results indicate that CNVs in AZF regions can be generated by microhomology-mediated break-induced replication in the absence of known rearrangement-inducing DNA features. AZFa-linked microduplications likely permit production of a normal amount of sperm, although the precise clinical consequences of these CNVs await further investigation.

  8. Levels and patterns of nucleotide variation in domestication QTL regions on rice chromosome 3 suggest lineage-specific selection.

    Directory of Open Access Journals (Sweden)

    Xianfa Xie

    Full Text Available Oryza sativa or Asian cultivated rice is one of the major cereal grass species domesticated for human food use during the Neolithic. Domestication of this species from the wild grass Oryza rufipogon was accompanied by changes in several traits, including seed shattering, percent seed set, tillering, grain weight, and flowering time. Quantitative trait locus (QTL mapping has identified three genomic regions in chromosome 3 that appear to be associated with these traits. We would like to study whether these regions show signatures of selection and whether the same genetic basis underlies the domestication of different rice varieties. Fragments of 88 genes spanning these three genomic regions were sequenced from multiple accessions of two major varietal groups in O. sativa--indica and tropical japonica--as well as the ancestral wild rice species O. rufipogon. In tropical japonica, the levels of nucleotide variation in these three QTL regions are significantly lower compared to genome-wide levels, and coalescent simulations based on a complex demographic model of rice domestication indicate that these patterns are consistent with selection. In contrast, there is no significant reduction in nucleotide diversity in the homologous regions in indica rice. These results suggest that there are differences in the genetic and selective basis for domestication between these two Asian rice varietal groups.

  9. Screening of YAC clones and building a map of the chromosome 13 region often deleted during chronic B-cell lymphocytic leucosis

    NARCIS (Netherlands)

    Brodyanskii, VM; Sulimova, GE; Udina, IG; Aitova, SS; Shaikhaev, GO; Sharikova, OA; Zakharev, VM; Fedorova, LI; Zelenin, AV; Eikhorn, S; Baush, C; Laland, M; Ross, M; Yankovskii, NK

    1995-01-01

    Pools of YAC clones from the ICRF library were analyzed by PCR using PBKpt, MGG15, and D13S25 markers that flank the chromosome 13 region often deleted during chronic lymphocytic leukemia. Ten clones were found and described. Nine mega-YAC clones from the CEPH library flanking the region of interest

  10. Yeast artificial chromosome contigs reveal that distal variable-region genes reside at least 3 megabases from the joining regions in the murine immunoglobulin kappa locus.

    Science.gov (United States)

    George, J B; Li, S; Garrard, W T

    1995-01-01

    The immunoglobulin kappa gene locus encodes 95% of the light chains of murine antibody molecules and is thought to contain up to 300 variable (V kappa)-region genes generally considered to comprise 20 families. To delineate the locus we have isolated 29 yeast artificial chromosome genomic clones that form two contigs, span > 3.5 megabases, and contain two known non-immunoglobulin kappa markers. Using PCR primers specific for 19 V kappa gene families and Southern analysis, we have refined the genetically defined order of these V kappa gene families. Of these, V kappa 2 maps at least 3.0 Mb from the joining (J kappa) region and appears to be the most distal V kappa gene segment. Images Fig. 3 Fig. 4 PMID:8618913

  11. Linkage between stature and a region on chromosome 20 and analysis of a candidate gene, bone morphogenetic protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, D.B.; Ossowski, V.; Janssen, R.C.; Knowler, W.C.; Bogardus, C. [National Inst. of Health, Phoenix, AZ (United States)

    1995-12-04

    Sib-pair linkage analysis of the quantitative trait, stature, in over 500 Pima Indians indicates that a genetic determinant of governing stature is located on chromosome 20. Analysis of 10 short tandem repeat polymorphisms localized this linkage to a 3. cM region that includes D20S98 and D20S66. Using all possible sib-pair combinations, linkage was detected to both stature (P = 0.0001) and to leg length (P = 0.001), but not to sitting height. Single-strand conformational polymorphism analysis of exon 3 of the bone morphogenetic protein 2 (BMP2) gene, a candidate gene in this region, in genomic DNA of 20 of the tallest and 20 of the shortest individuals did not show any consistent differences associated with leg length or height. Sequence analysis of the region encoding the mature protein revealed a single nucleotide substitution, a T to G transversion, not detected by single-strand conformational polymorphism (SSCP) analysis. This transversion results in a conservative amino acid substitution of glycine for valine at codon 80 of BMP2. The frequency of this allele was 0.23 in the sample. No significant differences in height were noted in persons carrying either allele. This indicates that this structural alteration in the mature BMP2 protein does not contribute to the differences in stature observed in the Pima Indians, nor is this structural change in the mature protein likely to be responsible for the linkage observed with stature on chromosome 20. 33 refs., 2 figs., 2 tabs.

  12. Similar frequency of paternal uniparental disomy involving chromosome 20q (patUPD20q) in Japanese and Caucasian patients affected by sporadic pseudohypoparathyroidism type Ib (sporPHP1B).

    Science.gov (United States)

    Takatani, Rieko; Minagawa, Masanori; Molinaro, Angelo; Reyes, Monica; Kinoshita, Kaori; Takatani, Tomozumi; Kazukawa, Itsuro; Nagatsuma, Misako; Kashimada, Kenichi; Sato, Kenichi; Matsushita, Kazuyuki; Nomura, Fumio; Shimojo, Naoki; Jüppner, Harald

    2015-10-01

    Pseudohypoparathyroidism type Ib (PHP1B) is caused by proximal tubular resistance to parathyroid hormone that occurs in most cases in the absence of Albright's Hereditary Osteodystrophy (AHO). Familial forms of PHP1B are caused by maternally inherited microdeletions within STX16, the gene encoding syntaxin 16, or within GNAS, a complex genetic locus on chromosome 20q13.3 encoding Gsα and several splice variants thereof. These deletions lead either to a loss-of-methylation affecting GNAS exon A/B alone or to epigenetic changes involving multiple differentially methylated regions (DMRs) within GNAS. Broad GNAS methylation abnormalities are also observed in most sporadic PHP1B (sporPHP1B) cases. However, with the exception of paternal uniparental disomy involving chromosome 20q (patUPD20q), the molecular mechanism leading to this disease variant remains unknown. We now investigated 23 Japanese sporPHP1B cases, who presented with hypocalcemia, hyperphosphatemia, elevated PTH levels, and occasionally with TSH elevations and mild AHO features. Age at diagnosis was 10.6 ± 1.45 years. Calcium, phosphate, and PTH were 6.3 ± 0.23 mg/dL, 7.7 ± 0.33 mg/dL, and 305 ± 34.5 pg/mL, respectively, i.e. laboratory findings that are indistinguishable from those previously observed for Caucasian sporPHP1B cases. All investigated patients showed broad GNAS methylation changes. Eleven individuals were homozygous for SNPs within exon NESP and a pentanucleotide repeat in exon A/B. Two of these patients furthermore revealed homozygosity for numerous microsatellite markers on chromosome 20q raising the possibility of patUPD20q, which was confirmed through the analysis of parental DNA. Based on this and our previous reports, paternal duplication of the chromosomal region comprising the GNAS locus appears to be a fairly common cause of sporPHP1B that is likely to occur with equal frequency in Caucasians and Asians.

  13. Comparative analysis of chicken chromosome 28 provides new clues to the evolutionary fragility of gene-rich vertebrate regions.

    Science.gov (United States)

    Gordon, Laurie; Yang, Shan; Tran-Gyamfi, Mary; Baggott, Dan; Christensen, Mari; Hamilton, Aaron; Crooijmans, Richard; Groenen, Martien; Lucas, Susan; Ovcharenko, Ivan; Stubbs, Lisa

    2007-11-01

    The chicken genome draft sequence has provided a valuable resource for studies of an important agricultural and experimental model species and an important data set for comparative analysis. However, some of the most gene-rich segments are missing from chicken genome draft assemblies, limiting the analysis of a substantial number of genes and preventing a closer look at regions that are especially prone to syntenic rearrangements. To facilitate the functional and evolutionary analysis of one especially gene-rich, rearrangement-prone genomic region, we analyzed sequence from BAC clones spanning chicken microchromosome GGA28; as a complement we also analyzed a gene-sparse, stable region from GGA11. In these two regions we documented the conservation and lineage-specific gain and loss of protein-coding genes and precisely mapped the locations of 31 major human-chicken syntenic breakpoints. Altogether, we identified 72 lineage-specific genes, many of which are found at or near syntenic breaks, implicating evolutionary breakpoint regions as major sites of genetic innovation and change. Twenty-two of the 31 breakpoint regions have been reused repeatedly as rearrangement breakpoints in vertebrate evolution. Compared with stable GC-matched regions, GGA28 is highly enriched in CpG islands, as are break-prone intervals identified elsewhere in the chicken genome; evolutionary breakpoints are further enriched in GC content and CpG islands, highlighting a potential role for these features in genome instability. These data support the hypothesis that chromosome rearrangements have not occurred randomly over the course of vertebrate evolution but are focused preferentially within "fragile" regions with unusual DNA sequence characteristics.

  14. A Narrow Segment of Maternal Uniparental Disomy of Chromosome 7q31-qter in Silver-Russell Syndrome Delimits a Candidate Gene Region

    Science.gov (United States)

    Hannula, Katariina; Lipsanen-Nyman, Marita; Kontiokari, Tero; Kere, Juha

    2001-01-01

    Maternal uniparental disomy of chromosome 7 (matUPD7), the inheritance of both chromosomes from only the mother, is observed in ∼10% of patients with Silver-Russell syndrome (SRS). It has been suggested that at least one imprinted gene that regulates growth and development resides on human chromosome 7. To date, three imprinted genes—PEG1/MEST, γ2-COP, and GRB10—have been identified on chromosome 7, but their role in the etiology of SRS remains uncertain. In a systematic screening with microsatellite markers, for matUPD7 cases among patients with SRS, we identified a patient who had a small segment of matUPD7 and biparental inheritance of the remainder of chromosome 7. Such a pattern may be explained by somatic recombination in the zygote. The matUPD7 segment at 7q31-qter extends for 35 Mb and includes the imprinted gene cluster of PEG1/MEST and γ2-COP at 7q32. GRB10 at 7p11.2-p12 is located within a region of biparental inheritance. Although partial UPD has previously been reported for chromosomes 6, 11, 14, and 15, this is the first report of a patient with SRS who has segmental matUPD7. Our findings delimit a candidate imprinted region sufficient to cause SRS. PMID:11112662

  15. Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder

    DEFF Research Database (Denmark)

    Rajkumar, A.P.; Christensen, Jane H.; Mattheisen, Manuel

    2015-01-01

    OBJECTIVES: Breakpoints of chromosomal abnormalities facilitate identification of novel candidate genes for psychiatric disorders. Genome-wide significant evidence supports the linkage between chromosome 17q25.3 and bipolar disorder (BD). Co-segregation of translocation t(9;17)(q33.2;q25.......3) with psychiatric disorders has been reported. We aimed to narrow down these chromosomal breakpoint regions and to investigate the associations between single nucleotide polymorphisms within these regions and BD as well as schizophrenia (SZ) in large genome-wide association study samples. METHODS: We cross......,856) data. Genetic associations between these disorders and single nucleotide polymorphisms within these breakpoint regions were analysed by BioQ, FORGE, and RegulomeDB programmes. RESULTS: Four protein-coding genes [coding for (endonuclease V (ENDOV), neuronal pentraxin I (NPTX1), ring finger protein 213...

  16. An autosomal recessive syndrome of severe mental retardation, cataract, coloboma and kyphosis maps to the pericentromeric region of chromosome 4.

    Science.gov (United States)

    Kahrizi, Kimia; Najmabadi, Hossein; Kariminejad, Roxana; Jamali, Payman; Malekpour, Mahdi; Garshasbi, Masoud; Ropers, Hans Hilger; Kuss, Andreas Walter; Tzschach, Andreas

    2009-01-01

    We report on three siblings with a novel mental retardation (MR) syndrome who were born to distantly related Iranian parents. The clinical problems comprised severe MR, cataracts with onset in late adolescence, kyphosis, contractures of large joints, bulbous nose with broad nasal bridge, and thick lips. Two patients also had uni- or bilateral iris coloboma. Linkage analysis revealed a single 10.4 Mb interval of homozygosity with significant LOD score in the pericentromeric region of chromosome 4 flanked by SNPs rs728293 (4p12) and rs1105434 (4q12). This interval contains more than 40 genes, none of which has been implicated in MR so far. The identification of the causative gene defect for this syndrome will provide new insights into the development of the brain and the eye.

  17. Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe

    DEFF Research Database (Denmark)

    Rietschel, M; Mattheisen, M; Degenhardt, F;

    2012-01-01

    Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture of schizophrenia (SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through...... an additional 2569 SCZ patients and 4088 controls (from Germany, The Netherlands and Denmark). Genetic variation in a region on chromosome 11 that contains the candidate genes AMBRA1, DGKZ, CHRM4 and MDK was significantly associated with SCZ in the combined sample (n=11 540; P=3.89 × 10(-9), odds ratio (OR)=1...... between emotion regulation and cognition that is structurally and functionally abnormal in SCZ and bipolar disorder.Molecular Psychiatry advance online publication, 12 July 2011; doi:10.1038/mp.2011.80....

  18. De novo LINE-1 retrotransposition in HepG2 cells preferentially targets gene poor regions of chromosome 13.

    Science.gov (United States)

    Bojang, Pasano; Anderton, Mark J; Roberts, Ruth A; Ramos, Kenneth S

    2014-08-01

    Long interspersed nuclear elements (Line-1 or L1s) account for ~17% of the human genome. While the majority of human L1s are inactive, ~80-100 elements remain retrotransposition competent and mobilize through RNA intermediates to different locations within the genome. De novo insertions of L1s account for polymorphic variation of the human genome and disruption of target loci at their new location. In the present study, fluorescence in situ hybridization and DNA sequencing were used to characterize retrotransposition profiles of L1(RP) in cultured human HepG2 cells. While expression of synthetic L1(RP) was associated with full-length and truncated insertions throughout the entire genome, a strong preference for gene-poor regions, such as those found in chromosome 13 was observed for full-length insertions. These findings shed light into L1 targeting mechanisms within the human genome and question the putative randomness of L1 retrotransposition.

  19. Genetic linkage mapping of the dehydroepiandrosterone sulfotransferase (STD) gene on the chromosome 19q13.3 region

    Energy Technology Data Exchange (ETDEWEB)

    Durocher, F.; Morissette, J.; Dufort, I.; Simard, J.; Luu-The, V. [Laval Univ. Quebec (Canada)

    1995-10-10

    In the human liver and adrenal, there is a single hydroxysteroid sulfotransferase, which catalyzes the transformation of dehydroepiandrosterone to dehydroepiandrosterone sulfate, the most abundantly circulating steroid in humans, and also catalyzes the sulfation of a series of other 3{beta}-hydroxysteroids as well as cholesterol. Dehydroepiandrosterone sulfate serves as precursor for the formation of active androgens and estrogens in several peripheral tissues, indicating that hydroxysteroid sulfotransferase plays a pivotal role in controlling the hormonal action of sex steroids by regulating their bioavailability. We recently elucidated the structure of the gene encoding hydroxysteroid sulfotransferase (STD), also designated dehydroepiandrosterone sulfotransferase, which spans 17 kb and contains six exons. The STD gene was preliminarily assigned to chromosome 19 by polymerase chain reaction (PCR) amplification of DNA from a panel of human/rodent somatic cell hybrids. To locate the STD gene, the novel biallelic polymorphism found in intron 2 was genotyped in eight CEPH reference families by direct sequencing of PCR products. Two-point linkage analysis was first performed between the latter polymorphism and chromosome 19 markers from Genethon and NIH/CEPH. The closest linkage was observed with D19S412 (Z{sub max} = 9.23; {theta}{sub max} 0.038) and HRC (Z{sub max} =5.95; {theta}{sub max}0.036), located on the 19q13.3 region. A framework map including six Genethon markers flanking the polymorphic STD gene was created by multipoint linkage analysis. Thereafter, a high-resolution genetic map of the region was constructed, yielding to the following order: qter-D19S414-D19S224-D19S420-D19S217-(APOC2-D19S412)-(STD-HRC)-KLK-D19S22-D19S180-PRKCG-D19S418-tel. 24 refs., 2 figs.

  20. Gene-rich chromosomal regions are preferentially localized in the lamin B deficient nuclear blebs of atypical progeria cells.

    Science.gov (United States)

    Bercht Pfleghaar, Katrin; Taimen, Pekka; Butin-Israeli, Veronika; Shimi, Takeshi; Langer-Freitag, Sabine; Markaki, Yolanda; Goldman, Anne E; Wehnert, Manfred; Goldman, Robert D

    2015-01-01

    More than 20 mutations in the gene encoding A-type lamins (LMNA) cause progeria, a rare premature aging disorder. The major pathognomonic hallmarks of progeria cells are seen as nuclear deformations or blebs that are related to the redistribution of A- and B-type lamins within the nuclear lamina. However, the functional significance of these progeria-associated blebs remains unknown. We have carried out an analysis of the structural and functional consequences of progeria-associated nuclear blebs in dermal fibroblasts from a progeria patient carrying a rare point mutation p.S143F (C428T) in lamin A/C. These blebs form microdomains that are devoid of major structural components of the nuclear envelope (NE)/lamina including B-type lamins and nuclear pore complexes (NPCs) and are enriched in A-type lamins. Using laser capture microdissection and comparative genomic hybridization (CGH) analyses, we show that, while these domains are devoid of centromeric heterochromatin and gene-poor regions of chromosomes, they are enriched in gene-rich chromosomal regions. The active form of RNA polymerase II is also greatly enriched in blebs as well as nascent RNA but the nuclear co-activator SKIP is significantly reduced in blebs compared to other transcription factors. Our results suggest that the p.S143F progeria mutation has a severe impact not only on the structure of the lamina but also on the organization of interphase chromatin domains and transcription. These structural defects are likely to contribute to gene expression changes reported in progeria and other types of laminopathies.

  1. Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes

    Science.gov (United States)

    Sarahan, Kari A.; Fisler, Janis S.

    2011-01-01

    We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions. PMID:21730028

  2. Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes.

    Science.gov (United States)

    Sarahan, Kari A; Fisler, Janis S; Warden, Craig H

    2011-09-22

    We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions.

  3. Pasture names with Romance and Slavic roots facilitate dissection of Y chromosome variation in an exclusively German-speaking alpine region.

    Directory of Open Access Journals (Sweden)

    Harald Niederstätter

    Full Text Available The small alpine district of East Tyrol (Austria has an exceptional demographic history. It was contemporaneously inhabited by members of the Romance, the Slavic and the Germanic language groups for centuries. Since the Late Middle Ages, however, the population of the principally agrarian-oriented area is solely Germanic speaking. Historic facts about East Tyrol's colonization are rare, but spatial density-distribution analysis based on the etymology of place-names has facilitated accurate spatial mapping of the various language groups' former settlement regions. To test for present-day Y chromosome population substructure, molecular genetic data were compared to the information attained by the linguistic analysis of pasture names. The linguistic data were used for subdividing East Tyrol into two regions of former Romance (A and Slavic (B settlement. Samples from 270 East Tyrolean men were genotyped for 17 Y-chromosomal microsatellites (Y-STRs and 27 single nucleotide polymorphisms (Y-SNPs. Analysis of the probands' surnames revealed no evidence for spatial genetic structuring. Also, spatial autocorrelation analysis did not indicate significant correlation between genetic (Y-STR haplotypes and geographic distance. Haplogroup R-M17 chromosomes, however, were absent in region A, but constituted one of the most frequent haplogroups in region B. The R-M343 (R1b clade showed a marked and complementary frequency distribution pattern in these two regions. To further test East Tyrol's modern Y-chromosomal landscape for geographic patterning attributable to the early history of settlement in this alpine area, principal coordinates analysis was performed. The Y-STR haplotypes from region A clearly clustered with those of Romance reference populations and the samples from region B matched best with Germanic speaking reference populations. The combined use of onomastic and molecular genetic data revealed and mapped the marked structuring of the distribution

  4. Pasture Names with Romance and Slavic Roots Facilitate Dissection of Y Chromosome Variation in an Exclusively German-Speaking Alpine Region

    Science.gov (United States)

    Niederstätter, Harald; Rampl, Gerhard; Erhart, Daniel; Pitterl, Florian; Oberacher, Herbert; Neuhuber, Franz; Hausner, Isolde; Gassner, Christoph; Schennach, Harald; Berger, Burkhard; Parson, Walther

    2012-01-01

    The small alpine district of East Tyrol (Austria) has an exceptional demographic history. It was contemporaneously inhabited by members of the Romance, the Slavic and the Germanic language groups for centuries. Since the Late Middle Ages, however, the population of the principally agrarian-oriented area is solely Germanic speaking. Historic facts about East Tyrol's colonization are rare, but spatial density-distribution analysis based on the etymology of place-names has facilitated accurate spatial mapping of the various language groups' former settlement regions. To test for present-day Y chromosome population substructure, molecular genetic data were compared to the information attained by the linguistic analysis of pasture names. The linguistic data were used for subdividing East Tyrol into two regions of former Romance (A) and Slavic (B) settlement. Samples from 270 East Tyrolean men were genotyped for 17 Y-chromosomal microsatellites (Y-STRs) and 27 single nucleotide polymorphisms (Y-SNPs). Analysis of the probands' surnames revealed no evidence for spatial genetic structuring. Also, spatial autocorrelation analysis did not indicate significant correlation between genetic (Y-STR haplotypes) and geographic distance. Haplogroup R-M17 chromosomes, however, were absent in region A, but constituted one of the most frequent haplogroups in region B. The R-M343 (R1b) clade showed a marked and complementary frequency distribution pattern in these two regions. To further test East Tyrol's modern Y-chromosomal landscape for geographic patterning attributable to the early history of settlement in this alpine area, principal coordinates analysis was performed. The Y-STR haplotypes from region A clearly clustered with those of Romance reference populations and the samples from region B matched best with Germanic speaking reference populations. The combined use of onomastic and molecular genetic data revealed and mapped the marked structuring of the distribution of Y

  5. Pasture names with Romance and Slavic roots facilitate dissection of Y chromosome variation in an exclusively German-speaking alpine region.

    Science.gov (United States)

    Niederstätter, Harald; Rampl, Gerhard; Erhart, Daniel; Pitterl, Florian; Oberacher, Herbert; Neuhuber, Franz; Hausner, Isolde; Gassner, Christoph; Schennach, Harald; Berger, Burkhard; Parson, Walther

    2012-01-01

    The small alpine district of East Tyrol (Austria) has an exceptional demographic history. It was contemporaneously inhabited by members of the Romance, the Slavic and the Germanic language groups for centuries. Since the Late Middle Ages, however, the population of the principally agrarian-oriented area is solely Germanic speaking. Historic facts about East Tyrol's colonization are rare, but spatial density-distribution analysis based on the etymology of place-names has facilitated accurate spatial mapping of the various language groups' former settlement regions. To test for present-day Y chromosome population substructure, molecular genetic data were compared to the information attained by the linguistic analysis of pasture names. The linguistic data were used for subdividing East Tyrol into two regions of former Romance (A) and Slavic (B) settlement. Samples from 270 East Tyrolean men were genotyped for 17 Y-chromosomal microsatellites (Y-STRs) and 27 single nucleotide polymorphisms (Y-SNPs). Analysis of the probands' surnames revealed no evidence for spatial genetic structuring. Also, spatial autocorrelation analysis did not indicate significant correlation between genetic (Y-STR haplotypes) and geographic distance. Haplogroup R-M17 chromosomes, however, were absent in region A, but constituted one of the most frequent haplogroups in region B. The R-M343 (R1b) clade showed a marked and complementary frequency distribution pattern in these two regions. To further test East Tyrol's modern Y-chromosomal landscape for geographic patterning attributable to the early history of settlement in this alpine area, principal coordinates analysis was performed. The Y-STR haplotypes from region A clearly clustered with those of Romance reference populations and the samples from region B matched best with Germanic speaking reference populations. The combined use of onomastic and molecular genetic data revealed and mapped the marked structuring of the distribution of Y

  6. Control regions for chromosome replication are conserved with respect to both sequence and location between Escherichia coli strains

    DEFF Research Database (Denmark)

    Frimodt-Møller, Jakob; Charbon, Godefroid; Krogfelt, Karen Angeliki;

    2015-01-01

    In Escherichia coli, chromosome replication is initiated from oriC by the DnaA initiator protein associated with ATP. Three non-coding regions contribute to the activity of DnaA. The datA locus is instrumental in conversion of DnaAATP to DnaAADP (DDAH; datA dependent DnaAATP hydrolysis) whereas Dna......A rejuvenation sequences 1 and 2 (DARS1 and DARS2) reactivate DnaAADP to DnaAATP. The structural organization of oriC, datA, DARS1 and DARS2 were found conserved between 59 fully sequenced E. coli genomes, with differences primarily in the non-functional spacer regions between key protein binding sites....... Competition experiments during balanced growth in rich medium and during mouse colonization indicated roles of datA, DARS1 and DARS2 for bacterial fitness although the relative contribution of each region differed between growth conditions. We suggest that this fitness cost contribute to conservation of both...

  7. Overlapping chromosomal regions for fertility traits and production traits in the Danish Holstein population

    DEFF Research Database (Denmark)

    Höglund, Johanna Karolina; Buitenhuis, A J; Guldbrandtsen, B;

    2009-01-01

    , it is of interest to validate which of the subtraits are affected by the QTL. Phenotypic and marker data were collected from 34 grandsire families from the Danish Holstein population. First, the trait data for "fertility treatments" were separated into their underlying subtraits: uterine infections, antibiotics...... placed in the placenta, and abortions. In addition, retained placenta was selected for analysis because it is related to uterine infections. A genome scan was performed using 416 microsatellite markers for the fertility treatment subtraits and retained placenta, and an additional genome scan for milk...... production traits conditional on the QTL regions for the subtraits and retained placenta was conducted. Second, we selected 24 genomic regions harboring QTL for fertility traits from a previous study. A QTL scan for milk production traits conditional on the selected regions was conducted. We found that 16...

  8. Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q

    NARCIS (Netherlands)

    Geremek, Maciej; Schoenmaker, Frederieke; Zietkiewicz, Ewa; Pogorzelski, Andrzej; Diehl, Scott; Wijmenga, Cisca; Witt, Michal

    2008-01-01

    Primary ciliary dyskinesia (PCD) is a rare genetic disorder, which shows extensive genetic heterogeneity and is mostly inherited in an autosomal recessive fashion. There are four genes with a proven pathogenetic role in PCD. DNAH5 and DNAI1 are involved in 28 and 10% of PCD cases, respectively, whil

  9. A variant of the H6 homeobox gene maps to the 10q25.1-q26.2 region of human chromosome 10

    Energy Technology Data Exchange (ETDEWEB)

    Stadler, H.S.; Solursh, M. [Univ. of Iowa, Iowa City, IA (United States); Goodfellow, P.J. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1994-09-01

    Homeobox genes represent a class of transcription factors which play a major role in the regulation of embryogenesis. Utilizing primers based on the conserved regions of the H6 homeobox gene, we were able to amplify several H6-like homeobox sequences from human genomic DNA. Analysis of these sequences indicated that at least 3 distinct H6-like homeobox regions may be present in Homo sapiens. From these distinct homeobox regions, primers were selected to screen a CEPH mega-YAC library for genomic clones containing the variant H6-like sequences. These screenings identified a YAC clone (YH6var) which contained the variant H6-like homeobox sequence. Utilizing a human/rodent somatic cell panel (Coriell B), the end clones from YH6var were chromosomally mapped to human chromosomes 10 and 16, indicating that YH6var was chimeric. An additional sequence flanking the H6 variant homeobox region was derived by inverse-PCR using YH6var as a template. From this flanking sequence, Homo sapien-specific primers were selected to assign the H6 variant to human chromosome 10 using the same Coriell B panel. The H6 variant gene was sublocalized to the 10q25.1-q26.2 region using a panel of somatic cell hybrids that retain well-characterized deletions/derivatives of chromosome 10. We are currently screening for STS-based markers for genetic linkage studies to confirm our physical mapping to the 10q25.1-q26.2 region as well as for use in linkage studies with developmental defects mapping to the same chromosomal region.

  10. Subnuclear relocalization and silencing of a chromosomal region by an ectopic ribosomal DNA repeat

    DEFF Research Database (Denmark)

    Jakociunas, Tadas; Domange Jordö, Marie Elise; Mebarek, Mazhoura Aït;

    2013-01-01

    dimerization, providing a mechanism for the observed relocalization. Replacing the full rDNA repeat with Reb1-binding sites, and using mutants lacking the histone H3K9 methyltransferase Clr4, indicated that the relocalized region was silenced redundantly by heterochromatin and another mechanism, plausibly...

  11. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    Directory of Open Access Journals (Sweden)

    Wang Jun

    2009-03-01

    Full Text Available Abstract Background A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular response to external damaging agents and markers in it are associated with risk of several cancers. Methods We downloaded the genotypes of all markers typed in the 19q13.3 region in the HapMap populations of European, Asian and African descent and inferred haplotypes. We combined the European HapMap individuals with a Danish breast cancer case-control data set and inferred the association between HapMap haplotypes and disease risk. Results We found that the susceptibility haplotype in our European sample had increased from 2 to 50 percent very recently in the European population, and to almost the same extent in the Asian population. The cause of this increase is unknown. The maximal proportion of overall genetic variation due to differences between groups for Europeans versus Africans and Europeans versus Asians (the Fst value closely matched the putative location of the susceptibility variant as judged from haplotype-based association mapping. Conclusion The combined observation that a common haplotype causing an increased risk of cancer in Europeans and a high differentiation between human populations is highly unusual and suggests a causal relationship with a recent increase in Europeans caused either by genetic drift overruling selection against the susceptibility variant or a positive selection for the same haplotype. The data does not allow us to distinguish between these two scenarios. The analysis suggests that the region is not involved in cancer risk in Africans and that the susceptibility variants may be more finely mapped in Asian populations.

  12. Narrowing the Duane syndrome critical region at chromosome 8q13 down to 40 kb.

    Science.gov (United States)

    Calabrese, G; Telvi, L; Capodiferro, F; Morizio, E; Pizzuti, A; Stuppia, L; Bordoni, R; Ion, A; Fantasia, D; Mingarelli, R; Palka, G

    2000-05-01

    Duane syndrome (MIM 126800) is an autosomal dominant disorder characterised by primary strabismus and other ocular anomalies, associated with variable deficiency of binocular sight. We have recently identified a syndrome carrying a reciprocal translation t(6;8)(q26;q13). FISH and PCR analyses using a YAC contig spanning the SRO narrowed the Duane region to a < 1 cM interval between markers SHGC37325 and W14901. In addition, the identification and mapping of two PAC clones flanking the translocation breakpoint, allowed us to further narrow the critical region to about 40 kb. As part of these mapping studies, we have also refined the map position of AMYB, a putative candidate gene, to 8q13, centromeric to Duane locus. AMYB is expressed in brain cortex and genital crests and has been previously mapped to 8q22.

  13. Characterization of the hemA-prs region of the Escherichia coli and Salmonella typhimurium chromosomes

    DEFF Research Database (Denmark)

    Post, David A.; Hove-Jensen, Bjarne; Switzer, Robert L.

    1993-01-01

    The prs gene, encoding phosphoribosylpyrophosphate synthetase, is preceded by a leader, which is 302 bp long in Escherichia coli and 417 bp in Salmonella typhimurium. A potential open reading frame (ORF) extends across the prs promoter and into the leader. The region between the prs coding region...... direction as the prs gene with ORF 2 extending into the prs leader. Northern blot analysis showed that the prs message in E. coli was on 1.3 and 2.7 kb transcripts. The shorter transcript encoded the prs gene only, while the longer transcript also encoded the two ORFs. Thus, the prs gene is transcribed from...... two promoters, the first promoter (P1) originating upstream of ORF 1, and expressing the prs gene in a tricistronic operon and a second promoter (P2), located within the ORF 2 coding frame, which transcribes the prs gene only. The transcripts encoding prs only were 20 times as abundant...

  14. Characterization of the genomic organization of the region bordering the centromere of chromosome V of Podospora anserina by direct sequencing.

    Science.gov (United States)

    Silar, Philippe; Barreau, Christian; Debuchy, Robert; Kicka, Sébastien; Turcq, Béatrice; Sainsard-Chanet, Annie; Sellem, Carole H; Billault, Alain; Cattolico, Laurence; Duprat, Simone; Weissenbach, Jean

    2003-08-01

    A Podospora anserina BAC library of 4800 clones has been constructed in the vector pBHYG allowing direct selection in fungi. Screening of the BAC collection for centromeric sequences of chromosome V allowed the recovery of clones localized on either sides of the centromere, but no BAC clone was found to contain the centromere. Seven BAC clones containing 322,195 and 156,244bp from either sides of the centromeric region were sequenced and annotated. One 5S rRNA gene, 5 tRNA genes, and 163 putative coding sequences (CDS) were identified. Among these, only six CDS seem specific to P. anserina. The gene density in the centromeric region is approximately one gene every 2.8kb. Extrapolation of this gene density to the whole genome of P. anserina suggests that the genome contains about 11,000 genes. Synteny analyses between P. anserina and Neurospora crassa show that co-linearity extends at the most to a few genes, suggesting rapid genome rearrangements between these two species.

  15. Copy-number variations in Y-chromosomal azoospermia factor regions identified by multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    Saito, Kazuki; Miyado, Mami; Kobori, Yoshitomo; Tanaka, Yoko; Ishikawa, Hiromichi; Yoshida, Atsumi; Katsumi, Momori; Saito, Hidekazu; Kubota, Toshiro; Okada, Hiroshi; Ogata, Tsutomu; Fukami, Maki

    2015-03-01

    Although copy-number variations (CNVs) in Y-chromosomal azoospermia factor (AZF) regions have been associated with the risk of spermatogenic failure (SF), the precise frequency, genomic basis and clinical consequences of these CNVs remain unclear. Here we performed multiplex ligation-dependent probe amplification (MLPA) analysis of 56 Japanese SF patients and 65 control individuals. We compared the results of MLPA with those of conventional sequence-tagged site PCR analyses. Eleven simple and complex CNVs, including three hitherto unreported variations, were identified by MLPA. Seven of the 11 CNVs were undetectable by conventional analyses. CNVs were widely distributed in AZF regions and shared by ~60% of the patients and ~40% of the controls. Most breakpoints resided within locus-specific repeats. The majority of CNVs, including the most common gr/gr deletion, were identified in the patient and control groups at similar frequencies, whereas simple duplications were observed exclusively in the patient group. The results imply that AZF-linked CNVs are more frequent and heterogeneous than previously reported. Non-allelic homologous recombination likely underlies these CNVs. Our data confirm the functional neutrality of the gr/gr deletion in the Japanese population. We also found a possible association between AZF-linked simple duplications and SF, which needs to be evaluated in future studies.

  16. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  17. 3D/4D architecture of chromosomal break point regions in the cell nucleus following irradiation of normal cells and tumor cells; 3D/4D Architektur von chromosomalen Bruchpunktregionen im Zellkern nach Bestrahlung von Normalzellen und Tumorzellen

    Energy Technology Data Exchange (ETDEWEB)

    Hausmann, M.; Cremer, C.; Friedl, A.; Dollinger, G.; Loebrich, M.; Friedland, W.

    2015-01-15

    The development of an effective analytical methodology for a correct description of oncogenic chromosomal aberrations is the challenge of medical radiobiology with respect to preventive therapeutic methods. Scope of the project was a better understanding of the behavior of break point regions dependent on the genome loci, the chromatin folding, the involved repair proteins and the beam quality with respect to an improvement and an efficient prognosis of the health consequences following radiation exposure. New microscopic insights in the normal cell nucleus are supposed to allow a better understanding of the spatial interactions on a molecular scale.

  18. Improving global and regional resolution of male lineage differentiation by simple single-copy Y-chromosomal short tandem repeat polymorphisms

    NARCIS (Netherlands)

    M. Vermeulen (Mark); A. Wollstein (Andreas); K. van der Gaag (Kristiaan); O. Lao Grueso (Oscar); Y. Xue (Yali); Q. Wang (Qiuju); L. Roewer (Lutz); H. Knoblauch (Hans); C. Tyler-Smith (Chris); P. de Knijff (Peter); M.H. Kayser (Manfred)

    2009-01-01

    textabstractWe analyzed 67 short tandem repeat polymorphisms from the non-recombining part of the Y-chromosome (Y-STRs), including 49 rarely studied simple single-copy (ss)Y-STRs and 18 widely used Y-STRs, in 590 males from 51 populations belonging to 8 worldwide regions (HGDP-CEPH panel). Although

  19. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    NARCIS (Netherlands)

    Wei-Yu Lin; N.J. Camp (Nicola); M. Ghoussaini (Maya); J. Beesley (Jonathan); K. Michailidou (Kyriaki); J. Hopper (John); C. Apicella (Carmel); M.C. Southey (Melissa); J. Stone (Jennifer); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.J. van 't Veer (Laura); E.J. Th Rutgers (Emiel J.); K.R. Muir (K.); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias W.); J. Peto (Julian); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); N. Johnson (Nichola); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); E.J. Sawyer (Elinor); T. Cheng (Timothy); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); Frederik Marmé; H. Surowy (Harald); B. Burwinkel (Barbara); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); C. Mulot (Claire); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); H. Anton-Culver (Hoda); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); P. Lichtner (Peter); R.K. Schmutzler (Rita); B. Müller-Myhsok (B.); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); C. Blomqvist (Carl); S. Khan (Sofia); K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hisato); A. Horio (Akiyo); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); A.H. Wu (Anna H.); C.-C. Tseng (Chiu-chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); P. Neven (Patrick); E. Wauters (Erwin); H. Wildiers (Hans); D. Lambrechts (Diether); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Bonnani (Bernardo); F.J. Couch (Fergus); X. Wang (Xianshu); C. Vachon (Celine); K. Purrington (Kristen); G.G. Giles (Graham G.); R.L. Milne (Roger L.); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); S.-H. Teo; C.H. Yip (Cheng Har); N. Hassan (Norhashimah); E.N. Vithana (Eranga); V. Kristensen (Vessela); W. Zheng (Wei); S.L. Deming-Halverson (Sandra); M. Shrubsole (Martha); J. Long (Jirong); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); J. Lissowska (Jolanta); L.A. Brinton (Louise); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J.S. Brand (Judith S.); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. Van DenOuweland (Ans M.W.); A. Jager (Agnes); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y. Gao; H. Cai (Hui); S.S. Cross (Simon); M.W.R. Reed (Malcolm); W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); P.D.P. Pharoah (Paul); B. Perkins (Barbara); M. Shah (Mitul); F. Blows (Fiona); D. Kang (Daehee); K.Y. Yoo; D-Y. Noh (Dong-Young); J.M. Hartman (Joost); X. Miao; K.S. Chia (Kee Seng); T.C. Putti (Thomas Choudary); U. Hamann (Ute); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); S. Slager (Susan); A.E. Toland (Amanda); D. Yannoukakos (Drakoulis); C-Y. Shen (Chen-Yang); C.-N. Hsiung (Chia-Ni); P.-E. Wu (Pei-Ei); S.-L. Ding (Shian-Ling); A. Ashworth (Alan); M. Jones (Michael); N. Orr (Nick); A.J. Swerdlow (Anthony ); H. Tsimiklis (Helen); E. Makalic (Enes); D.F. Schmidt (Daniel); Q.M. Bui (Quang); S.J. Chanock (Stephen); D. Hunter (David); R. Hein (Rebecca); N. Dahmen (N.); L. Beckmann (Lars); K. Aaltonen (Kirsimari); T.A. Muranen (Taru); T. Heikkinen (Tuomas); A. Irwanto (Astrid); N. Rahman (Nazneen); C. Turnbull (Clare); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); M.A. Adank (Muriel); R. Van Der Luijt (Rob); P. Hall (Per); G. Chenevix-Trench (Georgia); A.M. Dunning (Alison); D.F. Easton (Douglas); A. Cox (Angela)

    2015-01-01

    textabstractPrevious studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucl

  20. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    NARCIS (Netherlands)

    Wei-Yu Lin, Lin; Camp, Nicola J.; Ghoussaini, Maya; Beesley, Jonathan; Michailidou, Kyriaki; Hopper, John L.; Apicella, Carmel; Southey, Melissa C.; Stone, Jennifer; Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.; Th Rutgers, Emiel J.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Cheng, Timothy; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Frederik Marmé, Marmé; Surowy, Harald M.; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Mulot, Claire; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Pilar Zamora, M.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Álvarez, Nuria; Herrero, Daniel; Anton-Culver, Hoda; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon Dschun; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu Chen; Van Den Berg, David; Stram, Daniel O.; Neven, Patrick; Wauters, Els; Wildiers, Hans; Lambrechts, Diether; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Purrington, Kristen; Giles, Graham G.; Milne, Roger L.; Mclean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Marchand, Loic Le; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Hassan, Norhashimah; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Hooning, Maartje J.; Hollestelle, Antoinette; Van DenOuweland, Ans M W; Jager, Agnes; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao Ou; Lu, Wei; Gao, Yu Tang; Cai, Hui; Cross, Simon S.; Reed, Malcolm W R; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D P; Perkins, Barbara; Shah, Mitul; Blows, Fiona M.; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Putti, Thomas Choudary; Hamann, Ute; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen Yang; Hsiung, Chia Ni; Wu, Pei Ei; Ding, Shian Ling; Ashworth, Alan; Jones, Michael; Orr, Nick; Swerdlow, Anthony J.; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel F.; Bui, Quang M.; Chanock, Stephen J.; Hunter, David J.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Muranen, Taru A.; Heikkinen, Tuomas; Irwanto, Astrid; Rahman, Nazneen; Turnbull, Clare A.; Waisfisz, Quinten; Meijers-Heijboer, Hanne E J; Adank, Muriel A.; Van Der Luijt, Rob B.; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison; Easton, Douglas F.; Cox, Angela

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polym

  1. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    DEFF Research Database (Denmark)

    Lin, Wei-Yu; Camp, Nicola J; Ghoussaini, Maya

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide po...

  2. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

    Directory of Open Access Journals (Sweden)

    Blandine Patillon

    Full Text Available VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2 is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK. This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8, and PRSS8 with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  3. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

    Science.gov (United States)

    Patillon, Blandine; Luisi, Pierre; Blanché, Hélène; Patin, Etienne; Cann, Howard M; Génin, Emmanuelle; Sabbagh, Audrey

    2012-01-01

    VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2) is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK). This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8), and PRSS8) with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  4. Studies of X inactivation and isodisomy in twins provide further evidence that the X chromosomes is not involved in Rett syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Migeon, B.R.; Dunn, M.A.; Schmeckpeper, B.J.; Naidu, S. [Johns Hophins Univ., Baltimore, MD (United States); Thomas, G. [Johns Hopkins Univ., Baltimore, MD (United States)]|[Kennedy-Kreiger Institute, Baltimore, MD (United States)

    1995-03-01

    Rett syndrome (RS), a progressive encephalopathy with onset in infancy, has been attributed to an X-linked mutation, mainly on the basis of its occurrence almost exclusively in females and its concordance in female MZ twins. The underlying mechanisms proposed are an X-linked dominant mutation with male lethality, uniparental disomy of the X chromosome, and/or some disturbance in the process of X inactivation leading to unequal distribution of cells expressing maternal or paternal alleles (referred to as a {open_quotes}nonrandom{close_quotes} or {open_quotes}skewed {close_quotes} inactivation). To determine if the X chromosome is in fact involved in RS, we studied a group of affected females including three pairs of MZ twins, two concordant for RS and one uniquely discordant for RS. Analysis of X-inactivation patterns confirms the frequent nonrandom X inactivation previously observed in MZ twins but indicates that this is independent of RS. Analysis of 29 RS females reveals not one instance of uniparental X disomy, extending the observations previously reported. Therefore, our findings contribute no support for the hypothesis that RS is an X-linked disorder. Furthermore, the concordant phenotype in most MZ females twins with RS, which has not been observed in female twins with known X-linked mutations, argues against an X mutation. 41 refs., 2 figs.

  5. Investigation of LDHA and COPB1 as candidate genes for muscle development in the MYOD1 region of pig chromosome 2.

    Science.gov (United States)

    Qiu, Haifeng; Xu, Xuewen; Fan, Bing; Rothschild, Max F; Martin, Yerle; Liu, Bang

    2010-01-01

    Porcine MYOD1 gene has been mapped to swine chromosome (SSC) 2p14-p17, which is involved in the regulation of the proliferation and differentiation of skeletal muscle cells. The LDHA (lactate dehydrogenase A) and COPB1 (coatomer protein complex, subunit beta 1) genes, which map close to MYOD1, are involved in energy metabolism and protein transport processes. Both genes might play important roles in muscle development. However, little is known about the porcine LDHA and COPB1 genes. In the present study, the full-length cDNA of these two genes were cloned. The mapping results demonstrated that porcine LDHA and COPB1 were all mapped to SSC 2p14-p17. In this region, there are several QTL for growth and carcass traits, including average backfat thickness, lean and fat percentage. The RT-PCR results revealed that both LDHA and COPB1 were highly expressed in porcine skeletal muscle tissues, implying their potential regulatory function of muscle development. LDHA and COPB1 were then mapped to the region and multipoint analyses generated a best sex-averaged map order of each gene between linked markers: MYOD1_75.2 cM _LDHA_79 cM _CSRP3_83.8 cM _TEF-1_86.5 cM _COPB1_90 cM. Association analyses revealed that the substitution of c.423A>G had a significant effect on average daily gain on test, average backfat thickness (BFT), loin muscle area, lumbar BFT, marbling score, tenth rib BFT, average drip loss and fiber type II ratio. The substitution of c.3096C>T had a significant effect on average BFT, lumbar BFT, tenth rib BFT, carcass weight and last rib BFT. Interestingly, both SNPs were all associated with average BFT, lumbar BFT and tenth rib BFT.

  6. Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity.

    Science.gov (United States)

    Gericke, G S

    2010-05-01

    Previous reports of specific patterns of increased fragility at common chromosomal fragile sites (CFS) found in association with certain neurobehavioural disorders did not attract attention at the time due to a shift towards molecular approaches to delineate neuropsychiatric disorder candidate genes. Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the

  7. Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women

    Directory of Open Access Journals (Sweden)

    Alison L. Van Dyke

    2009-01-01

    Full Text Available In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC risk among Caucasian (364 cases; 380 controls and African American (95 cases; 103 controls women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotypes in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration.

  8. Roles of the Y chromosome genes in human cancers

    Directory of Open Access Journals (Sweden)

    Tatsuo Kido

    2015-06-01

    Full Text Available Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development (previously termed as an intersex condition with dysgenic gonads. Failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor (GCT, such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.

  9. Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, A.B. [Columbia Univ. School of Public Health, New York, NY (United States)

    1995-08-14

    Vitamin A (retinoid), an essential nutrient for fetal and subsequent mammalian development, is involved in gene expression, cell differentiation, proliferation, migration, and death. Retinoic acid (RA) the morphogenic derivative of vitamin A is highly teratogenic. In humans retinoid excess or deficit can result in brain anomalies and psychosis. This review discusses chromosomal loci of genes that control the retinoid cascade in relation to some candidate genes in schizophrenia. The paper relates the knowledge about the transport, delivery, and action of retinoids to what is presently known about the pathology of schizophrenia, with particular reference to the dopamine hypothesis, neurotransmitters, the glutamate hypothesis, neurotransmitters, the glutamate hypothesis, retinitis pigmentosa, dermatologic disorders, and craniofacial anomalies. 201 refs., 1 tab.

  10. Most significant genome regions involved in the control of earliness traits in bread wheat, as revealed by QTL meta-analysis.

    Science.gov (United States)

    Hanocq, E; Laperche, A; Jaminon, O; Lainé, A-L; Le Gouis, J

    2007-02-01

    Earliness is one of the most important adaptation traits in plant breeding. Our purpose was to identify the genome regions of bread wheat involved in the control of earliness and its three components: photoperiod sensitivity (PS), vernalization requirement (VR) and intrinsic earliness (IE). A QTL meta-analysis was carried out to examine the replicability of QTL across 13 independent studies and to propose meta-QTL (MQTL). Initial QTL were projected on a recent consensus map (2004). Quality criteria were proposed to assess the reliability of this projection. These criteria were based on the distances between markers in the QTL regions. Chromosomes of groups 2 and 5 had a greater incidence on earliness control as they carry the known, major genes Ppd and Vrn. Other chromosome regions played an intermediate role in earliness control: 4A [heading date (HD) Meta-QTL], 4B (HD MQTL), 2B (VR MQTL) and 5B (IE MQTL). Markers at this four MQTL should prove helpful in marker-assisted selection, to better control earliness.

  11. Haplotype frequencies in a sub-region of chromosome 19q13.3, related to risk and prognosis of cancer, differ dramatically between ethnic groups

    DEFF Research Database (Denmark)

    Schierup, M.H.; Mailund, T.; Li, H.

    2009-01-01

    Background: A small region of about 70 kb on human chromosome 19q13.3 encompasses 4 genes of which 3, ERCC1, ERCC2, and PPP1R13L (aka RAI) are related to DNA repair and cell survival, and one, CD3EAP, aka ASE1, may be related to cell proliferation. The whole region seems related to the cellular r...

  12. Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone

    OpenAIRE

    Lehner, Burkhard; Kunz, Pierre; Saehr, Heiner; Fellenberg, Joerg

    2014-01-01

    Background Growing evidence exists that the neoplastic stromal cell population (GCTSC) within giant cell tumors (GCT) originates from mesenchymal stem cells (MSC). In a previous study we identified a microRNA signature that differentiates between these cell types. Five differentially expressed microRNAs are located within the Dlk1-Dio3 region on chromosome 14. Aberrant regulation within this region is known to influence cell growth, differentiation and the development of cancer. The aim of th...

  13. Placental hydroxymethylation vs methylation at the imprinting control region 2 on chromosome 11p15.5

    Directory of Open Access Journals (Sweden)

    H.R. Magalhaes

    2013-11-01

    Full Text Available In addition to methylated cytosines (5-mCs, hydroxymethylcytosines (5-hmCs are present in CpG dinucleotide-enriched regions and some transcription regulator binding sites. Unlike methylation, hydroxymethylation does not result in silencing of gene expression, and the most commonly used methods to study methylation, such as techniques based on restriction enzymatic digestion and/or bisulfite modification, are unable to distinguish between them. Genomic imprinting is a process of gene regulation where only one member of an allelic pair is expressed depending on the parental origin. Chromosome 11p15.5 has an imprinting control region (ICR2 that includes a differentially methylated region (KvDMR1 that guarantees parent-specific gene expression. The objective of the present study was to determine the presence of 5-hmC at the KvDMR1 in human placentas. We analyzed 16 third-trimester normal human placentas (chorionic villi. We compared two different methods based on real-time PCR after enzymatic digestion. The first method distinguished methylation from hydroxymethylation, while the other method did not. Unlike other methylation studies, subtle variations of methylation in ICRs could represent a drastic deregulation of the expression of imprinted genes, leading to important phenotypic consequences, and the presence of hydroxymethylation could interfere with the results of many studies. We observed agreement between the results of both methods, indicating the absence of hydroxymethylation at the KvDMR1 in third-trimester placentas. To the best of our knowledge, this is the first study describing the investigation of hydroxymethylation in human placenta using a genomic imprinting model.

  14. Placental hydroxymethylation vs methylation at the imprinting control region 2 on chromosome 11p15.5.

    Science.gov (United States)

    Magalhães, H R; Leite, S B P; Paz, C C P de; Duarte, G; Ramos, E S

    2013-10-22

    In addition to methylated cytosines (5-mCs), hydroxymethylcytosines (5-hmCs) are present in CpG dinucleotide-enriched regions and some transcription regulator binding sites. Unlike methylation, hydroxymethylation does not result in silencing of gene expression, and the most commonly used methods to study methylation, such as techniques based on restriction enzymatic digestion and/or bisulfite modification, are unable to distinguish between them. Genomic imprinting is a process of gene regulation where only one member of an allelic pair is expressed depending on the parental origin. Chromosome 11p15.5 has an imprinting control region (ICR2) that includes a differentially methylated region (KvDMR1) that guarantees parent-specific gene expression. The objective of the present study was to determine the presence of 5-hmC at the KvDMR1 in human placentas. We analyzed 16 third-trimester normal human placentas (chorionic villi). We compared two different methods based on real-time PCR after enzymatic digestion. The first method distinguished methylation from hydroxymethylation, while the other method did not. Unlike other methylation studies, subtle variations of methylation in ICRs could represent a drastic deregulation of the expression of imprinted genes, leading to important phenotypic consequences, and the presence of hydroxymethylation could interfere with the results of many studies. We observed agreement between the results of both methods, indicating the absence of hydroxymethylation at the KvDMR1 in third-trimester placentas. To the best of our knowledge, this is the first study describing the investigation of hydroxymethylation in human placenta using a genomic imprinting model.

  15. Systematic characterisation of disease associated balanced chromosome rearrangements by FISH: cytogenetically and genetically anchored YACs identify microdeletions and candidate regions for mental retardation genes

    DEFF Research Database (Denmark)

    Wirth, J; Nothwang, H G; van der Maarel, S

    1999-01-01

    Disease associated balanced chromosome rearrangements (DBCRs) have been instrumental in the isolation of many disease genes. To facilitate the molecular cytogenetic characterisation of DBCRs, we have generated a set of >1200 non-chimeric, cytogenetically and genetically anchored CEPH YACs, on ave...... of disease in seemingly balanced chromosome rearrangements that are associated with a disease phenotype. Our region specific FISH probes, which are available to MCN members, can be a powerful tool in clinical cytogenetics and positional cloning.......Disease associated balanced chromosome rearrangements (DBCRs) have been instrumental in the isolation of many disease genes. To facilitate the molecular cytogenetic characterisation of DBCRs, we have generated a set of >1200 non-chimeric, cytogenetically and genetically anchored CEPH YACs...

  16. Haplotypes for 13 Y-chromosomal STR loci in South Tunisian population (Sfax region).

    Science.gov (United States)

    Ayadi, Imen; Ammar-Keskes, Leila; Rebai, Ahmed

    2006-12-20

    Nine Y-STR loci from the "minimal haplotype" (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393) included in Y-STR Haplotype Reference Databases (YHRD) with 4 additional Y-STRs (DYS436, DYS437, DYS438, DYS439) were analyzed by PCR using duplex and Y-PLEX 12 kit, followed by automatic genotyping in a sample of 105 Tunisian males originating from Sfax region (south Tunisia). Allelic frequencies and gene diversities for each Y-STR locus were determined. The high haplotype diversity (0.9932) and discrimination capacity (0.7714) show the usefulness of these loci for human identification in forensic studies and paternity tests in Tunisia. The most common haplotype was shared by 4.7% (5 individuals) of the sample was only found in samples from the Tunisian population reported in YHRD. One private allele for DYS392 (allele 17) was discovered and duplications were observed for five loci (DYS19, DYS389I, DYS393, DYS437 and DYS439).

  17. Y-chromosomal microsatellite diversity in three culturally defined regions of historical Tibet.

    Science.gov (United States)

    Gayden, Tenzin; Bukhari, Areej; Chennakrishnaiah, Shilpa; Stojkovic, Oliver; Herrera, Rene J

    2012-07-01

    In the present study, we analyzed 17 Y-STR loci in 350 Tibetan males from three culturally defined regions of historical Tibet: Amdo (88), Kham (109) and U-Tsang (153). A total of 299 haplotypes were observed, 272 (90.9%) of which were unique. Only one Y-STR profile is shared across the three Tibetan groups and, incidentally, is also the most frequent haplotype (4.0%), represented by two, five and seven individuals from U-Tsang, Kham and Amdo, respectively. The overall haplotype diversity for the three Tibetan populations at 17 Y-STR loci was 0.9978 and the corresponding values for the extended (11-loci) and minimal (9-loci) haplotypes were 0.9935 and 0.9909, respectively. Both neighbor-joining and Rst pairwise analyses suggest a close genetic relationship between the Amdo and Kham populations, while U-Tsang is genetically distinct from the aforementioned groups. The results demonstrate that the 17 Y-STR loci analyzed are highly polymorphic in all three Tibetan populations examined and hence useful for forensic cases, paternity testing and population genetic studies.

  18. Cortical regions involved in the generation of musical structures during improvisation in pianists.

    Science.gov (United States)

    Bengtsson, Sara L; Csíkszentmihályi, Mihály; Ullén, Fredrik

    2007-05-01

    Studies on simple pseudorandom motor and cognitive tasks have shown that the dorsolateral prefrontal cortex and rostral premotor areas are involved in free response selection. We used functional magnetic resonance imaging to investigate whether these brain regions are also involved in free generation of responses in a more complex creative behavior: musical improvisation. Eleven professional pianists participated in the study. In one condition, Improvise, the pianist improvised on the basis of a visually displayed melody. In the control condition, Reproduce, the participant reproduced his previous improvisation from memory. Participants were able to reproduce their improvisations with a high level of accuracy, and the contrast Improvise versus Reproduce was thus essentially matched in terms of motor output and sensory feedback. However, the Improvise condition required storage in memory of the improvisation. We therefore also included a condition FreeImp, where the pianist improvised but was instructed not to memorize his performance. To locate brain regions involved in musical creation, we investigated the activations in the Improvise-Reproduce contrast that were also present in FreeImp contrasted with a baseline rest condition. Activated brain regions included the right dorsolateral prefrontal cortex, the presupplementary motor area, the rostral portion of the dorsal premotor cortex, and the left posterior part of the superior temporal gyrus. We suggest that these regions are part of a network involved in musical creation, and discuss their possible functional roles.

  19. The Consolidation of Object and Context Recognition Memory Involve Different Regions of the Temporal Lobe

    Science.gov (United States)

    Balderas, Israela; Rodriguez-Ortiz, Carlos J.; Salgado-Tonda, Paloma; Chavez-Hurtado, Julio; McGaugh, James L.; Bermudez-Rattoni, Federico

    2008-01-01

    These experiments investigated the involvement of several temporal lobe regions in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of rats immediately after the sample phase of object or object-in-context recognition memory…

  20. Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15

    Directory of Open Access Journals (Sweden)

    Sigman Marian

    2008-01-01

    Full Text Available Abstract Background Maternally-derived duplications that include the imprinted region on the proximal long arm of chromosome 15 underlie a complex neurobehavioral disorder characterized by cognitive impairment, seizures and a substantial risk for autism spectrum disorders1. The duplications most often take the form of a supernumerary pseudodicentric derivative chromosome 15 [der(15] that has been called inverted duplication 15 or isodicentric 15 [idic(15], although interstitial rearrangements also occur. Similar to the deletions found in most cases of Angelman and Prader Willi syndrome, the duplications appear to be mediated by unequal homologous recombination involving low copy repeats (LCR that are found clustered in the region. Five recurrent breakpoints have been described in most cases of segmental aneuploidy of chromosome 15q11-q13 and previous studies have shown that most idic(15 chromosomes arise through BP3:BP3 or BP4:BP5 recombination events. Results Here we describe four duplication chromosomes that show evidence of atypical recombination events that involve regions outside the common breakpoints. Additionally, in one patient with a mosaic complex der(15, we examined homologous pairing of chromosome 15q11-q13 alleles by FISH in a region of frontal cortex, which identified mosaicism in this tissue and also demonstrated pairing of the signals from the der(15 and the normal homologues. Conclusion Involvement of atypical BP in the generation of idic(15 chromosomes can lead to considerable structural heterogeneity.

  1. Evaluating the relationship between spermatogenic silencing of the X chromosome and evolution of the Y chromosome in chimpanzee and human.

    Science.gov (United States)

    Mulugeta Achame, Eskeatnaf; Baarends, Willy M; Gribnau, Joost; Grootegoed, J Anton

    2010-12-14

    Chimpanzees and humans are genetically very similar, with the striking exception of their Y chromosomes, which have diverged tremendously. The male-specific region (MSY), representing the greater part of the Y chromosome, is inherited from father to son in a clonal fashion, with natural selection acting on the MSY as a unit. Positive selection might involve the performance of the MSY in spermatogenesis. Chimpanzees have a highly polygamous mating behavior, so that sperm competition is thought to provide a strong selective force acting on the Y chromosome in the chimpanzee lineage. In consequence of evolution of the heterologous sex chromosomes in mammals, meiotic sex chromosome inactivation (MSCI) results in a transcriptionally silenced XY body in male meiotic prophase, and subsequently also in postmeiotic repression of the sex chromosomes in haploid spermatids. This has evolved to a situation where MSCI has become a prerequisite for spermatogenesis. Here, by analysis of microarray testicular expression data representing a small number of male chimpanzees and men, we obtained information indicating that meiotic and postmeiotic X chromosome silencing might be more effective in chimpanzee than in human spermatogenesis. From this, we suggest that the remarkable reorganization of the chimpanzee Y chromosome, compared to the human Y chromosome, might have an impact on its meiotic interactions with the X chromosome and thereby on X chromosome silencing in spermatogenesis. Further studies will be required to address comparative functional aspects of MSCI in chimpanzee, human, and other placental mammals.

  2. Evaluating the relationship between spermatogenic silencing of the X chromosome and evolution of the Y chromosome in chimpanzee and human.

    Directory of Open Access Journals (Sweden)

    Eskeatnaf Mulugeta Achame

    Full Text Available Chimpanzees and humans are genetically very similar, with the striking exception of their Y chromosomes, which have diverged tremendously. The male-specific region (MSY, representing the greater part of the Y chromosome, is inherited from father to son in a clonal fashion, with natural selection acting on the MSY as a unit. Positive selection might involve the performance of the MSY in spermatogenesis. Chimpanzees have a highly polygamous mating behavior, so that sperm competition is thought to provide a strong selective force acting on the Y chromosome in the chimpanzee lineage. In consequence of evolution of the heterologous sex chromosomes in mammals, meiotic sex chromosome inactivation (MSCI results in a transcriptionally silenced XY body in male meiotic prophase, and subsequently also in postmeiotic repression of the sex chromosomes in haploid spermatids. This has evolved to a situation where MSCI has become a prerequisite for spermatogenesis. Here, by analysis of microarray testicular expression data representing a small number of male chimpanzees and men, we obtained information indicating that meiotic and postmeiotic X chromosome silencing might be more effective in chimpanzee than in human spermatogenesis. From this, we suggest that the remarkable reorganization of the chimpanzee Y chromosome, compared to the human Y chromosome, might have an impact on its meiotic interactions with the X chromosome and thereby on X chromosome silencing in spermatogenesis. Further studies will be required to address comparative functional aspects of MSCI in chimpanzee, human, and other placental mammals.

  3. A rare case of a three way complex variant positive Philadelphia translocation involving chromosome (9;11;22)(q34;p15;q11) in chronic myeloid leukemia: A case report

    Science.gov (United States)

    Asif, Muhammad; Hussain, Abrar; Rasool, Mahmood

    2016-01-01

    The t(9;22)(q34;q11) translocation is present in 90–95% of patients with chronic myeloid leukemia (CML). Variant complex translocations have been observed in 5–8% of CML patients, in which a third chromosome other than (9;22) is involved. Imatinib mesylate is the first line breakpoint cluster region-Abelson gene (BCR/ABL)-targeted oral therapy for CML, and may produce a complete response in 70–80% of CML patients in the chronic phase. In the present study, a bone marrow sample was used for conventional cytogenetic analysis, and the fluorescence in situ hybridization (FISH) test was used for BCR/ABL gene detection. A hematological analysis was also performed to determine the white blood cell (WBC) count, red blood cell count, hemoglobin levels, packed and mean cell volumes, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and platelet values of the patient. The hematological analysis of the patient indicated the increased WBC of 186.5×103 cells/µl, and decreased hemoglobin levels of 11.1 g/dl. The FISH test revealed that 67% cells demonstrated BCR/ABL gene translocation. The patient was treated with 400 mg imatinib mesylate daily, and was monitored at various intervals over a 6-month period. The present study reports the rare case of a patient that demonstrates a three-way Philadelphia chromosome-positive translocation involving 46XY,t(9;11;22)(q34;p15;q11)[10], alongside CML in the chronic phase. The translocation was analyzed using cytogenetic and FISH tests. PMID:27602125

  4. Effect of the genetic background on recombination frequency in the cn-vg region of the second chromosome of natural populations of Drosophila melanogaster.

    Science.gov (United States)

    Hofmanová, J

    1975-01-01

    Newly established test stocks made it possible to follow the effect of three different defined genetic backgrounds (first and third chromosomes) on recombination frequency in the cn-vg region of the second chromosomes isolated from four natural populations of Drosophila melanogaster. One background was composed of the chromosomes with inversions obtained from the stock (see article) and another two backgrounds were of the standard type consisting one-half of the original chromosomes from the natural population and one-half of the chromosomes of the stocks Oregon R or Samarkand. Using the analysis of variance significant differences in RF values were found between and within populations and especially between the different backgrounds. Some simple and double interactions between the above factors played a role. The highest RF values were obtained on the background [corrected] with inversions. The effect of the different genetic backgrounds [corrected] by the action of the genetic modifiers of RF. The different genetic backgrounds affected the variations in RF values in individual populations and the different populations reacted differentially to the changed genetic background. The design of the experiment permitted an estimation of the causal compoenents of variance and heritability of RF from the sib analysis. The additive component of variance was present in only two of the populations under test; the respective estimates of heritability were very low.

  5. Physical mapping of a large plant genome using global high-information-content-fingerprinting: the distal region of the wheat ancestor Aegilops tauschii chromosome 3DS

    Directory of Open Access Journals (Sweden)

    You Frank M

    2010-06-01

    Full Text Available Abstract Background Physical maps employing libraries of bacterial artificial chromosome (BAC clones are essential for comparative genomics and sequencing of large and repetitive genomes such as those of the hexaploid bread wheat. The diploid ancestor of the D-genome of hexaploid wheat (Triticum aestivum, Aegilops tauschii, is used as a resource for wheat genomics. The barley diploid genome also provides a good model for the Triticeae and T. aestivum since it is only slightly larger than the ancestor wheat D genome. Gene co-linearity between the grasses can be exploited by extrapolating from rice and Brachypodium distachyon to Ae. tauschii or barley, and then to wheat. Results We report the use of Ae. tauschii for the construction of the physical map of a large distal region of chromosome arm 3DS. A physical map of 25.4 Mb was constructed by anchoring BAC clones of Ae. tauschii with 85 EST on the Ae. tauschii and barley genetic maps. The 24 contigs were aligned to the rice and B. distachyon genomic sequences and a high density SNP genetic map of barley. As expected, the mapped region is highly collinear to the orthologous chromosome 1 in rice, chromosome 2 in B. distachyon and chromosome 3H in barley. However, the chromosome scale of the comparative maps presented provides new insights into grass genome organization. The disruptions of the Ae. tauschii-rice and Ae. tauschii-Brachypodium syntenies were identical. We observed chromosomal rearrangements between Ae. tauschii and barley. The comparison of Ae. tauschii physical and genetic maps showed that the recombination rate across the region dropped from 2.19 cM/Mb in the distal region to 0.09 cM/Mb in the proximal region. The size of the gaps between contigs was evaluated by comparing the recombination rate along the map with the local recombination rates calculated on single contigs. Conclusions The physical map reported here is the first physical map using fingerprinting of a complete

  6. A polymorphic and hypervariable locus in the pseudoautosomal region of the CBA/H mouse sex chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Fennelly, J.; Laval, S.; Wright, E.; Plumb, M. [MRC Radiation and Genomic Stability Unit, Oxon (United Kingdom)

    1996-04-01

    We have identified a genomic locus (DXYH1) that is polymorphic and hypervariable within the CBA/H colony. Using a panel of C57BL/6 x Mus spretus backcross offspring, it was mapped to the distal end of the X chromosome. Pseudoautosomal inheritance was demonstrated through three generations of CBA/H x CBA/H and CBA/H x C57BL/6 crosses and confirmed through linkage to the Sxr locus in X/Y Sxr x 3H1 crosses. Meiotic recombination frequencies place DXYH1 {approximately}28% into the pseudoautosomal region from the boundary. The de novo generation of CBA/H variant DXYH1 restriction fragment length polymorphisms during spermatogenesis is suggestive of the germline instability associated with hypermutable human minisatellites. The absence of DXY1-related sequences in Mus spretus provides DNA sequence evidence to support the observed failure of X-Y pairing during meiosis and consequent hybrid infertility in C57BL/6 x Mus spretus male F1 offspring. 19 refs., 4 figs.

  7. Genes encoding two lipoproteins in the leuS-dacA region of the Escherichia coli chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Takase, I.; Ishino, F.; Wachi, M.; Kamata, H.; Doi, M.; Asoh, S.; Matsuzawa, H.; Ohta, T.; Matsuhashi, M.

    1987-12-01

    The coding of two rare lipoproteins by two genes, rlpA and rlpB, located in the leuS-dacA region (15 min) on the Escherichia coli chromosome was demonstrated by expression of subcloned genes in a maxicell system. The formation of these two proteins was inhibited by globomycin, which is an inhibitor of the signal peptidase for the known lipoproteins of E. coli. In each case, this inhibition was accompanied by formation of a new protein, which showed a slightly lower mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and which we suppose to be a prolipoprotein with an N-terminal signal peptide sequence similar to those of the bacterial major lipoproteins and lysis proteins of some bacteriocins. The incorporation of /sup 3/H-labeled palmitate and glycerol into the two lipoproteins was also observed. Sequencing of DNA showed that the two lipoprotein genes contained sequences that could code for signal peptide sequences of 17 amino acids (rlpA lipoprotein) and 18 amino acids (rlpB lipoprotein). The deduced sequences of the mature peptides consisted of 345 amino acids (M/sub r/ 35,615, rlpA lipoprotein) and 175 amino acids (M/sub r/ 19,445, rlpB lipoprotein), with an N-terminal cysteine to which thioglyceride and N-fatty acyl residues may be attached. These two lioproteins may be important in duplication of the cells.

  8. Molecular cytogenetic characterization of a non-robertsonian dicentric chromosome 14;19 identified in a girl with short stature and amenorrhea.

    Science.gov (United States)

    Dutta, Usha R; Pidugu, Vijaya Kumar; Dalal, Ashwin

    2012-01-01

    We report a 16-year-old girl who presented with short stature and amenorrhea. Initially the cytogenetic analysis showed the presence of a mosaic non-Robertsonian dicentric chromosome involving chromosomes 14 and 19. Subsequent molecular cytogenetic analysis by fluorescence in situ hybridization (FISH) using whole chromosome paints, centromeric probes, as well as gene specific probes confirmed the dicentric nature of the derivative chromosome and indicated that the rearrangement involved the short arms of both of these chromosomes. Furthermore, we also determined that the chromosome 19p13.3 breakpoint occurred within the terminal 1 Mb region. This is the first report of a mosaic non-Robertsonian dicentric chromosome involving chromosomes 14 and 19 with the karyotype determined as 45,XX,dic(14;19)(p11.2;p13.3)[35]/46,XX[15], and we suggest that the chromosome rearrangement could be the cause of clinical phenotype.

  9. Molecular Cytogenetic Characterization of a Non-Robertsonian Dicentric Chromosome 14;19 Identified in a Girl with Short Stature and Amenorrhea

    Directory of Open Access Journals (Sweden)

    Usha R. Dutta

    2012-01-01

    Full Text Available We report a 16-year-old girl who presented with short stature and amenorrhea. Initially the cytogenetic analysis showed the presence of a mosaic non-Robertsonian dicentric chromosome involving chromosomes 14 and 19. Subsequent molecular cytogenetic analysis by fluorescence in situ hybridization (FISH using whole chromosome paints, centromeric probes, as well as gene specific probes confirmed the dicentric nature of the derivative chromosome and indicated that the rearrangement involved the short arms of both of these chromosomes. Furthermore, we also determined that the chromosome 19p13.3 breakpoint occurred within the terminal 1 Mb region. This is the first report of a mosaic non-Robertsonian dicentric chromosome involving chromosomes 14 and 19 with the karyotype determined as 45,XX,dic(14;19(p11.2;p13.3[35]/46,XX[15], and we suggest that the chromosome rearrangement could be the cause of clinical phenotype.

  10. Mapping of the human dentin matrix acidic phosphoprotein gene (DMP1) to the dentinogenesis imperfecta type II critical region at chromosome 4q21

    Energy Technology Data Exchange (ETDEWEB)

    Aplin, H.M.; Hirst, K.L.; Crosby, A.H.; Dixon, M.J. [Univ. of Manchester (United Kingdom)

    1995-11-20

    Dentinogenesis imperfecta type II (DGI1) is an autosomal dominant disorder of dentin formation, which has been mapped to human chromosome 4q12-q21. The region most likely to contain the DGI1 locus is a 3.2-cM region surrounding the osteopontin (SPP1) locus. Recently, a novel dentin-specific acidic phosphoprotein (dmp1) has been cloned in the rat and mapped to mouse chromosome 5q21. In the current investigation, we have isolated a cosmid containing the human DMP1 gene. The isolation of a short tandem repeat polymorphism at this locus has allowed us to map the DMP1 locus to human chromosome 4q21 and demonstrate that it is tightly linked to DGI1 in two families (Z{sub max} = 11.01, {theta} = 0.001). The creation of a yeast artificial chromosome contig around SPP1 has further allowed us to demonstrate that DMP1 is located within 150 kb of the bone sialoprotein and 490 kb of the SPP1 loci, respectively. DMP1 is therefore a strong candidate for the DGI1 locus. 12 refs., 2 figs., 1 tab.

  11. Sex-determining Region of Y Chromosome-related High-mobility-group Box 2 in Malignant Tumors: Current Opinions and Anticancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Shi-Guang Cao; Zong-Juan Ming; Yu-Ping Zhang; Shuan-Ying Yang

    2015-01-01

    Objective:To gain insight into the mechanism by which sex-determining region of Y chromosome (SRY)-related high-mobility-group box 2 (SOX2) involved in carcinogenesis and cancer stem cells (CSCs).Data Sources:The data used in this review were mainly published in English from 2000 to present obtained from PubMed.The search terms were "SOX2," "cancer," "tumor" or "CSCs."Study Selection:Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed.Results:SOX2,a transcription factor that is the key in maintaining pluripotent properties of stem cells,is a member of SRy-related high-mobility group domain proteins.SOX2 participates in many biological processes,such as modulation of cell proliferation,regulation of cell death signaling,cell apoptosis,and most importantly,tumor formation and development.Although SOX2 has been implicated in the biology of various tumors and CSCs,the findings are highly controversial,and information regarding the underlying mechanism remains limited.Moreover,the mechanism by which SOX2 involved in carcinogenesis and tumor progression is rather unclear yet.Conclusions:Here,we review the important biological functions of SOX2 in different tumors and CSCs,and the function of SOX2 signaling in the pathobiology ofneoplasia,such as Wnt/β-catenin signaling pathway,Hippo signaling pathway,Survivin signaling pathway,PI3K/Akt signaling pathway,and so on.Targeting towards SOX2 may be an effective therapeutic strategy for cancer therapy.

  12. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.

    Science.gov (United States)

    Lin, Wei-Yu; Camp, Nicola J; Ghoussaini, Maya; Beesley, Jonathan; Michailidou, Kyriaki; Hopper, John L; Apicella, Carmel; Southey, Melissa C; Stone, Jennifer; Schmidt, Marjanka K; Broeks, Annegien; Van't Veer, Laura J; Th Rutgers, Emiel J; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Sawyer, Elinor J; Cheng, Timothy; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marmé, Frederik; Surowy, Harald M; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Mulot, Claire; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, M Pilar; Arias Perez, Jose Ignacio; Menéndez, Primitiva; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Alvarez, Nuria; Herrero, Daniel; Anton-Culver, Hoda; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K; Müller-Myhsok, Bertram; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Wauters, Els; Wildiers, Hans; Lambrechts, Diether; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Purrington, Kristen; Giles, Graham G; Milne, Roger L; Mclean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Hassan, Norhashimah; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J; García-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S; Hooning, Maartje J; Hollestelle, Antoinette; Van Den Ouweland, Ans M W; Jager, Agnes; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cross, Simon S; Reed, Malcolm W R; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Pharoah, Paul D P; Perkins, Barbara; Shah, Mitul; Blows, Fiona M; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Putti, Thomas Choudary; Hamann, Ute; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Ashworth, Alan; Jones, Michael; Orr, Nick; Swerdlow, Anthony J; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel F; Bui, Quang M; Chanock, Stephen J; Hunter, David J; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Muranen, Taru A; Heikkinen, Tuomas; Irwanto, Astrid; Rahman, Nazneen; Turnbull, Clare A; Waisfisz, Quinten; Meijers-Heijboer, Hanne E J; Adank, Muriel A; Van Der Luijt, Rob B; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison; Easton, Douglas F; Cox, Angela

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10(-6)), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis.

  13. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    Science.gov (United States)

    Lin, Wei-Yu; Camp, Nicola J.; Ghoussaini, Maya; Beesley, Jonathan; Michailidou, Kyriaki; Hopper, John L.; Apicella, Carmel; Southey, Melissa C.; Stone, Jennifer; Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.; Th Rutgers, Emiel J.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Cheng, Timothy; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marmé, Frederik; Surowy, Harald M.; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Mulot, Claire; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Menéndez, Primitiva; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Álvarez, Nuria; Herrero, Daniel; Anton-Culver, Hoda; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O.; Neven, Patrick; Wauters, Els; Wildiers, Hans; Lambrechts, Diether; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Purrington, Kristen; Giles, Graham G.; Milne, Roger L.; Mclean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Hassan, Norhashimah; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Hooning, Maartje J.; Hollestelle, Antoinette; Van Den Ouweland, Ans M.W.; Jager, Agnes; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cross, Simon S.; Reed, Malcolm W. R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D.P.; Perkins, Barbara; Shah, Mitul; Blows, Fiona M.; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Putti, Thomas Choudary; Hamann, Ute; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-ling; Ashworth, Alan; Jones, Michael; Orr, Nick; Swerdlow, Anthony J; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel F.; Bui, Quang M.; Chanock, Stephen J.; Hunter, David J.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Muranen, Taru A.; Heikkinen, Tuomas; Irwanto, Astrid; Rahman, Nazneen; Turnbull, Clare A.; Waisfisz, Quinten; Meijers-Heijboer, Hanne E. J.; Adank, Muriel A.; Van Der Luijt, Rob B.; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison; Easton, Douglas F.; Cox, Angela

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03–1.07), P = 1 × 10−5. Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10−6), yielding a combined OR (95% CI) of 1.06 (1.04–1.08), P = 1 × 10−9. Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis. PMID:25168388

  14. Partitioning of the Linear Chromosome during Sporulation of Streptomyces coelicolor A3(2) Involves an oriC-Linked parAB Locus

    Science.gov (United States)

    Kim, Hyun-Jin; Calcutt, Michael J.; Schmidt, Francis J.; Chater, Keith F.

    2000-01-01

    Candidate partitioning genes (parA and parB) for the linear chromosome of Streptomyces coelicolor were identified by DNA sequencing in a series of seven genes located between rnpA and trxA near the chromosomal replication origin. The most likely translation start point of parB overlapped the parA stop codon, suggestive of coregulation, and transcription analysis suggested that the two genes formed an operon. Deletion of part of parB had no effect on the growth or appearance of colonies but caused a deficiency in DNA partitioning during the multiple septation events involved in converting aerial hyphae into long chains of spores. At least 13% of spore compartments failed to inherit the normal DNA allocation. The same phenotype was obtained with a deletion removing a segment of DNA from both parA and parB. Reinforcing the idea of a special role for the par locus during sporulation, the stronger of two parAB promoters was greatly upregulated at about the time when sporulation septation was maximal in colonies. Three copies of a 14-bp inverted repeat (GTTTCACGTGAAAC) were found in or near the parAB genes, and at least 12 more identical copies were identified within 100 kb of oriC from the growing genome sequence database. Only one perfect copy of the 14-bp sequence was present in approximately 5 Mb of sequence available from the rest of the genome. The 14-bp sequence was similar to sequences identified as binding sites for Spo0J, a ParB homologue from Bacillus subtilis believed to be important for DNA partitioning (D. C.-H. Lin and A. D. Grossman, Cell 92:675–685, 1998). One of these sites encompassed the transcription start point of the stronger parA promoter. PMID:10671452

  15. Genetic analyses involving microsatellite ETH10 genotypes on bovine chromosome 5 and performance trait measures in Angus- and Brahman-influenced cattle.

    Science.gov (United States)

    DeAtley, K L; Rincon, G; Farber, C R; Medrano, J F; Luna-Nevarez, P; Enns, R M; VanLeeuwen, D M; Silver, G A; Thomas, M G

    2011-07-01

    ETH10 is a dinucleotide microsatellite within the promoter of signal transducer and activator of transcription 6 (STAT6) gene on bovine chromosome 5. ETH10 is included in the panel of genetic markers used in parentage testing procedures of cattle breed associations. Allelic sizes of ETH10 PCR amplicons range from 199 to 225 bp. Objectives of this study were to use microsatellite data from beef cattle breed associations to investigate genetic distance and population stratification among Angus- and Brahman-influenced cattle and to use ETH10 genotypes and growth and ultrasound carcass data to investigate their statistical relationships. Three series of genotype to phenotype association analyses were conducted with 1) Angus data (n=5,094), 2) Brangus data (3/8 Brahman × 5/8 Angus; n=2,296), and 3) multibreed data (n=4,426) of Angus and Brangus cattle. Thirteen alleles and 38 genotypes were observed, but frequencies varied among breed groups. Tests of genetic identity and distance among 6 breed composition groups increasing in Brahman influence from 0 to 75% revealed that as Brahman-influence increased to ≥50%, genetic distance from Angus ranged from 18.3 to 43.5%. This was accomplished with 10 microsatellite loci. A mixed effects model involving genotype as a fixed effect and sire as a random source of variation suggested that Angus cattle with the 217/219 genotype tended to have 2.1% heavier (P=0.07) 205-d BW than other genotypes. In Brangus cattle, allele combinations were classified as small (≤215 bp) or large (≥217 bp). Brangus cattle with the small/large genotype had 2.0% heavier (Pcarcass traits in Angus and Brangus cattle. Results from this study provide support for STAT6 as one of the candidate genes underlying cattle growth QTL on chromosome 5.

  16. Noradrenergic mechanism involved in the nociceptive modulation of hippocampal CA3 region of normal rats.

    Science.gov (United States)

    Jin, Hua; Teng, Yueqiu; Zhang, Xuexin; Yang, Chunxiao; Xu, Manying; Yang, Lizhuang

    2014-06-27

    Norepinephrine (NE) is an important neurotransmitter in the brain, and regulates antinociception. However, the mechanism of action of NE on pain-related neurons in the hippocampal CA3 region is not clear. This study examines the effects of NE, phentolamine on the electrical activities of pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal CA3 region of rats. Trains of electric impulses applied to the right sciatic nerve were used as noxious stimulation. The electrical activities of PENs or PINs in the hippocampal CA3 region were recorded by using a glass microelectrode. Our results revealed that, in the hippocampal CA3 region, the intra-CA3 region microinjection of NE decreased the pain-evoked discharged frequency and prolonged the discharged latency of PEN, and increased the pain-evoked discharged frequency and shortened discharged inhibitory duration (ID) of PIN, exhibiting the specific analgesic effect of NE. While intra-CA3 region microinjection of phentolamine produced the opposite response. It implies that phentolamine can block the effect of endogenous NE to cause the enhanced response of PEN and PIN to noxious stimulation. On the basis of above findings we can deduce that NE, phentolamine and alpha-adrenoceptor are involved in the modulation of nociceptive information transmission in the hippocampal CA3 region.

  17. Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model.

    Directory of Open Access Journals (Sweden)

    Lucie Šedová

    Full Text Available Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16 and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx into the genomic background of the spontaneously hypertensive rat (SHR strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18-28 mmHg difference and diastolic (10-15 mmHg difference blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001. The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1. Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic

  18. Bacterial chromosome segregation.

    Science.gov (United States)

    Possoz, Christophe; Junier, Ivan; Espeli, Olivier

    2012-01-01

    Dividing cells have mechanisms to ensure that their genomes are faithfully segregated into daughter cells. In bacteria, the description of these mechanisms has been considerably improved in the recent years. This review focuses on the different aspects of bacterial chromosome segregation that can be understood thanks to the studies performed with model organisms: Escherichia coli, Bacillus subtilis, Caulobacter crescentus and Vibrio cholerae. We describe the global positionning of the nucleoid in the cell and the specific localization and dynamics of different chromosomal loci, kinetic and biophysic aspects of chromosome segregation are presented. Finally, a presentation of the key proteins involved in the chromosome segregation is made.

  19. Absence of Y chromosome in human placental site trophoblastic tumor.

    Science.gov (United States)

    Hui, Pei; Wang, Hanlin L; Chu, Peiguo; Yang, Bin; Huang, Jiaoti; Baergen, Rebecca N; Sklar, Jeffrey; Yang, Ximing J; Soslow, Robert A

    2007-10-01

    Placental site trophoblastic tumor is a neoplasm of extravillous intermediate trophoblast at the implantation site, preceded in the majority of cases by a female gestational event. Our pilot investigation suggested that the development of this tumor might require a paternally derived X chromosome and the absence of a Y chromosome. Twenty cases of placental site trophoblastic tumor were included in this study. Genotyping at 15 polymorphic loci and one sex determination locus was performed by multiplex PCR followed by capillary electrophoresis. X chromosome polymorphisms were determined by PCR amplification of exon 1 of the human androgen receptor gene using primers flanking the polymorphic CAG repeats within this region. Genotyping at 15 polymorphic loci was informative and paternal alleles were present in all tumors, confirming the trophoblastic origin of the tumors. The presence of an X chromosome and the absence of a Y chromosome were observed in all tumors. Among 13 cases in which analysis of the X chromosome polymorphism was informative, all but one demonstrated at least two X alleles and seven cases showed one identifiable paternal X allele. These results confirm a unique pathogenetic mechanism in placental site trophoblastic tumor, involving an exclusion of the Y chromosome from the genome and, therefore, a tumor arising from the trophectoderm of a female conceptus. As epigenetic regulations of imprinting during X chromosome inactivation are of significant biological implications, placental site trophoblastic tumor may provide an important model for studying the sex chromosome biology and the proliferative advantage conferred by the paternal X chromosome.

  20. Characterization of divIVA and other genes located in the chromosomal region downstream of the dcw cluster in Streptococcus pneumoniae.

    Science.gov (United States)

    Fadda, Daniela; Pischedda, Carla; Caldara, Fabrizio; Whalen, Michael B; Anderluzzi, Daniela; Domenici, Enrico; Massidda, Orietta

    2003-10-01

    We analyzed the chromosome region of Streptococcus pneumoniae located downstream of the division and cell wall (dcw) cluster that contains the homolog of the Bacillus subtilis cell division gene divIVA and some genes of unknown function. Inactivation of divIVA in S. pneumoniae resulted in severe growth inhibition and defects in cell shape, nucleoid segregation, and cell division. Inactivation of the ylm genes resulted in some morphological and/or division abnormalities, depending on the inactivated gene. Transcriptional analysis revealed a relationship between these genes and the ftsA and ftsZ cell division genes, also indicating that the connection between the dcw cluster and the divIVA region is more extensive than just chromosomal position and gene organization.

  1. A three-generation family with terminal microdeletion involving 5p15.33-32 due to a whole-arm 5;15 chromosomal translocation with a steady phenotype of atypical cri du chat syndrome.

    Science.gov (United States)

    Elmakky, Amira; Carli, Diana; Lugli, Licia; Torelli, Paola; Guidi, Battista; Falcinelli, Cristina; Fini, Sergio; Ferrari, Fabrizio; Percesepe, Antonio

    2014-03-01

    Cri du chat syndrome is characterized by cat-like cry, facial dysmorphisms, microcephaly, speech delay, intellectual disability and slow growth rate, which are present with variable frequency. The typical cri du chat syndrome, due to 5p15.2 deletion, includes severe intellectual disability, facial dysmorphisms, neonatal hypotonia and pre- and post-natal growth retardation, whereas more distal deletions in 5p15.3 lead to cat-like cry and speech delay and produce the clinical picture of the atypical cri du chat syndrome, with minimal or absent intellectual impairment. In this article we report a three-generation family with an unbalanced whole arm translocation between chromosome 5 and 15 and a microdeletion of 5.5 Mb involving 5p15.33-32. By reporting the smallest terminal deletion of 5p15.3 described so far and by reviewing the literature we discuss the genotype/phenotype correlations of the distal region of the cri du chat syndrome. The previously described critical region for the speech delay may be narrowed down and microcephaly, growth retardation and dysmorphic facial features can be included in the phenotypic expression of the atypical cri du chat syndrome due to 5p15.3 deletions.

  2. Xp11.2 translocation renal cell carcinoma occurring during pregnancy with a novel translocation involving chromosome 19: a case report with review of the literature

    Directory of Open Access Journals (Sweden)

    Surti Urvashi

    2009-05-01

    Full Text Available Abstract The recently recognized renal cell carcinomas (RCCs associated with Xp11.2 translocations (TFE3 transcription factor gene fusions are rare tumors predominantly reported in children. They comprise at least one-third of pediatric RCCs and only few adult cases have been reported. Here, we present a case of Xp11.2 translocation RCC in 26-year-old pregnant female. Her routine antenatal ultrasonography accidentally found a complex cystic right renal mass. Further radiologic studies revealed unilocular cyst with multiple mural nodules at inferior pole of right kidney, which was suspicious for RCC. She underwent right radical nephrectomy at 15 weeks gestation. Macroscopically, the cystic tumor was well encapsulated with multiple friable mural nodules on its inner surface. Microscopically, the tumor consisted of clear and eosinophilic/oncocytic voluminous cells arranged in papillary, trabecular, and nested/alveolar patterns. Occasional hyaline nodules and numerous psammoma bodies were present. Immunohistochemically, the tumor showed strong nuclear positivity for TFE3. Epithelial membrane antigen, CD10, and E-cadherin were strongly positive. Cytokeratin AE1/AE3, cytokeratin CAM-5.2, calveolin, and parvalbumin were moderately positive. Cytokeratin 7, renal cell carcinoma antigen, and colloidal iron were focally weakly positive. BerEP4 and carbonic anhydrase IX were negative. Cytogenetically, the tumor harbored a novel variant translocation involving chromosomes X and 19, t(X;19(p11.2;q13.1. Interphase FISH analysis performed on cultured and uncultured tumor cells using a dual-color break-apart DNA probe within the BCL3 gene on 19q13.3 was negative for the BCL3 gene rearrangement. She received no adjuvant therapy, delivered a normal term baby five months later, and is alive without evidence of disease 27 months after diagnosis and surgery. Unlike most recently reported Xp11.2 translocation RCCs in adult patients with aggressive clinical course

  3. Molecular characterization of HIV-1 subtype C gp-120 regions potentially involved in virus adaptive mechanisms.

    Directory of Open Access Journals (Sweden)

    Alessandra Cenci

    Full Text Available The role of variable regions of HIV-1 gp120 in immune escape of HIV has been investigated. However, there is scant information on how conserved gp120 regions contribute to virus escaping. Here we have studied how molecular sequence characteristics of conserved C3, C4 and V3 regions of clade C HIV-1 gp120 that are involved in HIV entry and are target of the immune response, are modulated during the disease course. We found an increase of "shifting" putative N-glycosylation sites (PNGSs in the α2 helix (in C3 and in C4 and an increase of sites under positive selection pressure in the α2 helix during the chronic stage of disease. These sites are close to CD4 and to co-receptor binding sites. We also found a negative correlation between electric charges of C3 and V4 during the late stage of disease counteracted by a positive correlation of electric charges of α2 helix and V5 during the same stage. These data allow us to hypothesize possible mechanisms of virus escape involving constant and variable regions of gp120. In particular, new mutations, including new PNGSs occurring near the CD4 and CCR5 binding sites could potentially affect receptor binding affinity and shield the virus from the immune response.

  4. Origin and domestication of papaya Yh chromosome.

    Science.gov (United States)

    VanBuren, Robert; Zeng, Fanchang; Chen, Cuixia; Zhang, Jisen; Wai, Ching Man; Han, Jennifer; Aryal, Rishi; Gschwend, Andrea R; Wang, Jianping; Na, Jong-Kuk; Huang, Lixian; Zhang, Lingmao; Miao, Wenjing; Gou, Jiqing; Arro, Jie; Guyot, Romain; Moore, Richard C; Wang, Ming-Li; Zee, Francis; Charlesworth, Deborah; Moore, Paul H; Yu, Qingyi; Ming, Ray

    2015-04-01

    Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XY(h)). The hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previously. We now report the sequence of the entire male-specific region of the Y (MSY). We used a BAC-by-BAC approach to sequence the MSY and resequence the Y regions of 24 wild males and the Y(h) regions of 12 cultivated hermaphrodites. The MSY and HSY regions have highly similar gene content and structure, and only 0.4% sequence divergence. The MSY sequences from wild males include three distinct haplotypes, associated with the populations' geographic locations, but gene flow is detected for other genomic regions. The Y(h) sequence is highly similar to one Y haplotype (MSY3) found only in wild dioecious populations from the north Pacific region of Costa Rica. The low MSY3-Y(h) divergence supports the hypothesis that hermaphrodite papaya is a product of human domestication. We estimate that Y(h) arose only ∼ 4000 yr ago, well after crop plant domestication in Mesoamerica >6200 yr ago but coinciding with the rise of the Maya civilization. The Y(h) chromosome has lower nucleotide diversity than the Y, or the genome regions that are not fully sex-linked, consistent with a domestication bottleneck. The identification of the ancestral MSY3 haplotype will expedite investigation of the mutation leading to the domestication of the hermaphrodite Y(h) chromosome. In turn, this mutation should identify the gene that was affected by the carpel-suppressing mutation that was involved in the evolution of males.

  5. Mapping of a chromosome 12 region associated with airway hyperresponsiveness in a recombinant congenic mouse strain and selection of potential candidate genes by expression and sequence variation analyses.

    Directory of Open Access Journals (Sweden)

    Cynthia Kanagaratham

    Full Text Available In a previous study we determined that BcA86 mice, a strain belonging to a panel of AcB/BcA recombinant congenic strains, have an airway responsiveness phenotype resembling mice from the airway hyperresponsive A/J strain. The majority of the BcA86 genome is however from the hyporesponsive C57BL/6J strain. The aim of this study was to identify candidate regions and genes associated with airway hyperresponsiveness (AHR by quantitative trait locus (QTL analysis using the BcA86 strain. Airway responsiveness of 205 F2 mice generated from backcrossing BcA86 strain to C57BL/6J strain was measured and used for QTL analysis to identify genomic regions in linkage with AHR. Consomic mice for the QTL containing chromosomes were phenotyped to study the contribution of each chromosome to lung responsiveness. Candidate genes within the QTL were selected based on expression differences in mRNA from whole lungs, and the presence of coding non-synonymous mutations that were predicted to have a functional effect by amino acid substitution prediction tools. One QTL for AHR was identified on Chromosome 12 with its 95% confidence interval ranging from 54.6 to 82.6 Mbp and a maximum LOD score of 5.11 (p = 3.68 × 10(-3. We confirmed that the genotype of mouse Chromosome 12 is an important determinant of lung responsiveness using a Chromosome 12 substitution strain. Mice with an A/J Chromosome 12 on a C57BL/6J background have an AHR phenotype similar to hyperresponsive strains A/J and BcA86. Within the QTL, genes with deleterious coding variants, such as Foxa1, and genes with expression differences, such as Mettl21d and Snapc1, were selected as possible candidates for the AHR phenotype. Overall, through QTL analysis of a recombinant congenic strain, microarray analysis and coding variant analysis we identified Chromosome 12 and three potential candidate genes to be in linkage with airway responsiveness.

  6. Detailed comparison between the wheat chromosome group 7 short arms and the rice chromosome arms 6S and 8L with special reference to genes involved in starch biosynthesis

    DEFF Research Database (Denmark)

    Li, Zhongyi; Huang, Bingyan; Rampling, Lynette;

    2004-01-01

    .4%) and a high level of chromosome rearrangements (68.6%). The non-syntenous loci were of two classes: wheat and rice genes found at different locations in the genome (32.6%), and ESTs in wheat not present in rice (36.0%). Four starch synthetic genes, GBSSI, SSI, SSIIa and DBEI, were located at similar positions...... to a complement of rice BACs. A virtual contig was used that covered 90 cM (21 Mb) of DNA sequence (with a gap for the 6S/8L junction). Comparison of the positions of orthologous genes on the rice virtual contig and on wheat chromosome 7AS showed that there was an unexpectedly low level of synteny (31...... on wheat chromosome 7AS and the virtual rice contig covering wheat chromosome 7AS. A preliminary comparison between the short arms of chromosome 7A and 7D in wheat showed that both chromosomes had a similar level of sequence synteny with rice. Therefore, there appears to be considerable variation in gene...

  7. Partner involvement in perinatal care and PMTCT services in Mbeya Region, Tanzania: the providers' perspective.

    Science.gov (United States)

    Theuring, Stefanie; Nchimbi, Philo; Jordan-Harder, Brigitte; Harms, Gundel

    2010-12-01

    Partner involvement is considered to increase the effectiveness of female-oriented services for sexual and reproductive health (SRH), like those for antenatal care (ANC) or the prevention of mother-to-child transmission of HIV (PMTCT). However, male participation rates remain mostly low, and previous research has identified restrictive provider attitudes among barriers for partner participation in such services. Individual perspectives and experiences of healthcare providers are assumed to significantly influence the quality of delivered services. This study aimed at exploring providers' attitudes regarding partner involvement in ANC/PMTCT and other SRH services. A hundred interviews based on a semi-structured questionnaire were conducted among healthcare providers employed in an ANC-based PMTCT program in Mbeya Region, Tanzania. Interviewees expressed overall approval of male partner integration into the services, but this approval decreased when specifying for different service types, especially in those related to perinatal examinations or labor and delivery. Divergence between general attitudes and self-reported individual behavior was observed, querying the reliability of expressed attitudes. Among providers having at least one child, personally experienced partner attendance and approval of partner involvement were significantly associated for most service types. Although general views on partner involvement in SRH services seem to be mostly supportive, there is a need for health services to strengthen providers' positions toward male involvement, for example by communicating clear policies and job guidelines, and by encouraging partner service attendance among providers themselves.

  8. The 172 kb prkA-addAB region from 83° to 97° of the Bacillus subtilis chromosome contains several dysfunctional genes, the glyB marker, many genes encoding transporter proteins, and the ubiquitous hit gene

    NARCIS (Netherlands)

    Noback, Michiel A.; Holsappel, Siger; Kiewiet, Rense; Terpstra, Peter; Wambutt, Rolf; Wedler, Holger; Venema, Gerard; Bron, Sierd

    1998-01-01

    A 171812 bp nucleotide sequence between prkA and addAB (83° to 97°) on the genetic map of the Bacillus subtilis 168 chromosome was determined and analysed. An accurate physical/genetic map of this previously poorly described chromosomal region was constructed. One hundred and seventy open reading fr

  9. The 172 kb prkA-addAB region from 83 degrees to 97 degrees of the Bacillus subtilis chromosome contains several dysfunctional genes, the glyB marker, many genes encoding transporter proteins, and the ubiquitous hit gene

    NARCIS (Netherlands)

    Noback, MA; Holsappel, S; Kiewiet, R; Terpstra, P; Wambutt, R; Wedler, H; Venema, G; Bron, S

    1998-01-01

    A 171812 bp nucleotide sequence between prkA and addAB (83 degrees to 97 degrees) on the genetic map of the Bacillus subtilis 168 chromosome was determined and analysed. An accurate physical/genetic map of this previously poorly described chromosomal region was constructed. One hundred and seventy o

  10. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  11. Characterization of the promoter region of biosynthetic enzyme genes involved in berberine biosynthesis in Coptis japonica

    Directory of Open Access Journals (Sweden)

    Yasuyuki Yamada

    2016-09-01

    Full Text Available The presence of alkaloids is rather specific to certain plant species. However, berberine, an isoquinoline alkaloid, is relatively broadly distributed in the plant kingdom. Thus, berberine biosynthesis has been intensively investigated, especially using Coptis japonica cell cultures. Almost all biosynthetic enzyme genes have already been characterized at the molecular level. Particularly, two transcription factors (TFs, a plant-specific WRKY-type transcription factor, CjWRKY1, and a basic helix-loop-helix (bHLH transcription factor, CjbHLH1, were shown to comprehensively regulate berberine biosynthesis in C. japonica cells. In this study, we characterized the promoter region of some biosynthetic enzyme genes and associated cis-acting elements involved in the transcriptional regulation via two TFs. The promoter regions of three berberine biosynthetic enzyme genes (CYP80B2, 4’OMT and CYP719A1 were isolated, and their promoter activities were dissected by a transient assay involving the sequentially truncated promoter::luciferase (LUC reporter constructs. Furthermore, transactivation activities of CjWRKY1 were determined using the truncated promoter::LUC reporter constructs or constructs with mutated cis-elements. These results suggest the involvement of a putative W-box in the regulation of biosynthetic enzyme genes. Direct binding of CjWRKY1 to the W-box DNA sequence was also confirmed by an electrophoresis mobility shift assay (EMSA and by a chromatin immunoprecipitation (ChIP assay. In addition, CjbHLH1 also activated transcription from truncated 4’OMT and CYP719A1 promoters independently of CjWRKY1, suggesting the involvement of a putative E-box. Unexpected transcriptional activation of biosynthetic enzyme genes via a non-W-box sequence and by CjWRKY1 as well as the possible involvement of a GCC-box in berberine biosynthesis in C. japonica are discussed.

  12. Increased chromosomal breakage in Tourette syndrome predicts the possibility of variable multiple gene involvement in spectrum phenotypes: Preliminary findings and hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Gericke, G.S.; Simonic, I.; Cloete, E.; Buckle, C. [Univ. of Pretoria (South Africa)] [and others

    1995-10-09

    Increased chromosomal breakage was found in 12 patients with DSM-IV Tourette syndrome (TS) as compared with 10 non-TS control individuals with respect to untreated, modified RPM1-, and BrdU treated lymphocyte cultures (P < 0.001 in each category). A hypothesis is proposed that a major TS gene is probably connected to genetic instability, and associated chromosomal marker sites may be indicative of the localization of secondary genes whose altered expression could be responsible for associated comorbid conditions. This concept implies that genes influencing higher brain functions may be situated at or near highly recombigenic areas allowing enhanced amplification, duplication and recombination following chromosomal strand breakage. Further studies on a larger sample size are required to confirm the findings relating to chromosomal breakage and to analyze the possible implications for a paradigmatic shift in linkage strategy for complex disorders by focusing on areas at or near unstable chromosomal marker sites. 32 refs., 1 tab.

  13. Microsatellite and single nucleotide polymorphisms in the β-globin locus control region-hypersensitive Site 2: SPECIFICITY of Tunisian βs chromosomes.

    Science.gov (United States)

    Ben Mustapha, Maha; Moumni, Imen; Zorai, Amine; Douzi, Kaïs; Ghanem, Abderraouf; Abbes, Salem

    2012-01-01

    The diversity of sickle cell disease severity is attributed to several cis acting factors, among them the single nucleotide polymorphisms (SNPs) and (AT) rich region in the β-locus control region (β-LCR). This contains five DNase I hypersensitive sites (HS) located 6 to 22 kb upstream to the ϵ gene. The most important of these is the HS2 (5' β-LCR-HS2), characterized by the presence of three different SNPs and a microsatellite region known to be in association with β(S) chromosomes in various populations. The aim of this study was to present the molecular investigation of the 5' β-LCR-HS2 site in normal and sickle cell disease individuals in order to determine if there is any correlation or specificity between these molecular markers, the β(S) Tunisian chromosomes and phenotypical expression of sickle cell disease. One hundred and twenty-four chromosomes from Tunisian individuals (49 β(S) carriers and 13 normal individuals) were screened by polymerase chain reaction (PCR) and sequencing for the polymorphic short tandem microsatellite repeats (AT)(X)N(12)(AT)(Y) and the three SNPs (rs7119428, rs9736333 and rs60240093) of the 5' β-LCR-HS2. Twelve configurations of the microsatellite motif were found with an ancestral configuration elaborated by ClustalW software. Normal and mutated alleles were observed at the homozygous and heterozygous states for the three SNPs. Correlation between microsatellites and SNPs suggests that mutant SNP alleles were mainly associated, in the homozygous sickle cell disease phenotype, with the (AT)(8)N(12)GT(AT)(7) configuration, whereas, normal SNP alleles were associated with the (AT)(X)N(12)(AT)(11) configurations in normal β(A) chromosomes. The correlation of these various configurations with Hb F expression was also investigated. The principal component analysis (PCA) showed the correlation between the homozygous sickle cell disease phenotype, mutated SNP alleles and the Benin microsatellite configuration (AT)(8)N(12)GT

  14. Identification of region-specific yeast artificial chromosomes using pools of Alu element-mediated polymerase chain reaction probes labeled via linear amplification

    Energy Technology Data Exchange (ETDEWEB)

    Cole, C.G.; Bobrow, M.; Bentley, D.R.; Dunham, I. (United Medical and Dental Schools of Guy' s and St. Thomas Hospitals, London Bridge, London, England (United Kingdom)); Patel, K.; Shipley, J.; Sheer, D. (Imperial Cancer Research Fund, London (United Kingdom))

    1992-12-01

    The ability to identify large numbers of yeast artificial chromosomes (YACS) specific to any given genomic region rapidly and efficiently enhances both the construction of clone maps and the isolation of region-specific landmarks (e.g., polymorphic markers). The authors describe a method of preparing region-specific single-stranded hybridization probes from Alu element-mediated polymerase chain reaction (Alu-PCR) products of somatic cell hybrids for YAC library screening. Pools of up to 50 cloned Alu-PCR products from an irradiation-reduced hybrid containing 22q11.2-q13.1 were labeled to high specific activity by linear amplification using a single vector primer. The resulting single-stranded probes were extensively competed to remove repetitive sequences, while retaining the full complexity of the probe. Extensive coverage of the region by YACs using multiple probe pools was demonstrated as many YACs were detected more than once. In situ analysis using chosen YACs confirmed that the clones were specific for the region. Thus, this pooled probe approach constitutes a rapid method to identify large numbers of YACs relevant to a large chromosomal region. 29 refs., 4 figs.

  15. Identification of region-specific yeast artificial chromosomes using pools of Alu element-mediated polymerase chain reaction probes labeled via linear amplification.

    Science.gov (United States)

    Cole, C G; Patel, K; Shipley, J; Sheer, D; Bobrow, M; Bentley, D R; Dunham, I

    1992-12-01

    The ability to identify large numbers of yeast artificial chromosomes (YACs) specific to any given genomic region rapidly and efficiently enhances both the construction of clone maps and the isolation of region-specific landmarks (e.g., polymorphic markers). We describe a method of preparing region-specific single-stranded hybridization probes from Alu element-mediated polymerase chain reaction (Alu-PCR) products of somatic cell hybrids for YAC library screening. Pools of up to 50 cloned Alu-PCR products from an irradiation-reduced hybrid containing 22q11.2-q13.1 were labeled to high specific activity by linear amplification using a single vector primer. The resulting single-stranded probes were extensively competed to remove repetitive sequences, while retaining the full complexity of the probe. Extensive coverage of the region by YACs using multiple probe pools was demonstrated as many YACs were detected more than once. In situ analysis using chosen YACs confirmed that the clones were specific for the region. Thus, this pooled probe approach constitutes a rapid method to identify large numbers of YACs relevant to a large chromosomal region.

  16. Proximity Within Interphase Chromosome Contributes to the Breakpoint Distribution in Radiation-Induced Intrachromosomal Exchanges

    Science.gov (United States)

    Zhang, Ye; Uhlemeyer, Jimmy; Hada, Megumi; Asaithamby, A.; Chen, David J.; Wu, Honglu

    2015-01-01

    Previously, we reported that breaks involved in chromosome aberrations were clustered in several regions of chromosome3 in human mammary epithelial cells after exposures to either low-or high-LET radiation. In particular, breaks in certain regions of the chromosome tended to rejoin with each other to form an intrachromosome exchange event. This study tests the hypothesis that proximity within a single chromosome in interphase cell nuclei contributes to the distribution of radiation-induced chromosome breaks. Chromosome 3 in G1 human mammary epithelial cells was hybridized with the multicolor banding in situ hybridization (mBAND) probes that distinguish the chromosome in six differently colored regions, and the location of these regions was measured with a laser confocal microscope. Results of the study indicated that, on a multi-mega base pair scale of the DNA, the arrangement of chromatin was non-random. Both telomere regions tended to be located towards the exterior of the chromosome domain, whereas the centromere region towards the interior. In addition, the interior of the chromosome domain was preferentially occupied by the p-arm of the chromatin, which is consistent with our previous finding of intrachromosome exchanges involving breaks on the p-arm and in the centromere region of chromosome3. Other factors, such as the fragile sites in the 3p21 band and gene regulation, may also contribute to the breakpoint distribution in radiation-induced chromosome aberrations. Further investigations suggest that the 3D chromosome folding is cell type and culture condition dependent.

  17. Single nucleotide polymorphisms in the REG-CTNNA2 region of chromosome 2 and NEIL3 associated with impulsivity in a Native American sample.

    Science.gov (United States)

    Ehlers, C L; Gizer, I R; Bizon, C; Slutske, W; Peng, Q; Schork, N J; Wilhelmsen, K C

    2016-07-01

    Impulsivity is a multi-faceted construct that, while characterized by a set of correlated dimensions, is centered around a core definition that involves acting suddenly in an unplanned manner without consideration for the consequences of such behavior. Several psychiatric disorders include impulsivity as a criterion, and thus it has been suggested that it may link a number of different behavioral disorders, including substance abuse. Native Americans (NA) experience some of the highest rates of substance abuse of all the US ethnic groups. The described analyses used data from a low-coverage whole genome sequence scan to conduct a genome-wide association study (GWAS) of an impulsivity phenotype in an American Indian community sample (n = 658). Demographic and clinical information were obtained using a semi-structured interview. Impulsivity was assessed using a scale derived from the Maudsley personality inventory that combines both novelty seeking and lack of planning items. The impulsivity score was tested for association with each variant adjusted for demographic variables, and corrected for ancestry and kinship, using emmax. Simulations were conducted to calculate empirical P-values. Genome-wide significant findings were observed for a variant 50-kb upstream from catenin cadherin-associated protein, alpha 2 (CTNNA2), a neuronal-specific catenin, in the REG gene cluster. A meta-analysis of GWAS had previously identified common variants in CTNNA2 as being associated with excitement seeking. A second locus upstream of nei endonuclease VIII-like 3 (NEIL3) on chromosome 4 also achieved genome-wide significance. The association between sequence variants in these regions suggests their potential roles in the genetic regulation of this phenotype in this population.

  18. Familial complex chromosomal rearrangement resulting in a recombinant chromosome.

    Science.gov (United States)

    Berend, Sue Ann; Bodamer, Olaf A F; Shapira, Stuart K; Shaffer, Lisa G; Bacino, Carlos A

    2002-05-15

    Familial complex chromosomal rearrangements (CCRs) are rare and tend to involve fewer breakpoints and fewer chromosomes than CCRs that are de novo in origin. We report on a CCR identified in a child with congenital heart disease and dysmorphic features. Initially, the child's karyotype was thought to involve a straightforward three-way translocation between chromosomes 3, 8, and 16. However, after analyzing the mother's chromosomes, the mother was found to have a more complex rearrangement that resulted in a recombinant chromosome in the child. The mother's karyotype included an inverted chromosome 2 and multiple translocations involving chromosomes 3, 5, 8, and 16. No evidence of deletion or duplication that could account for the clinical findings in the child was identified.

  19. Chromosome abnormalities in Indonesian patients with short stature

    Directory of Open Access Journals (Sweden)

    Paramayuda Chrysantine

    2012-08-01

    Full Text Available Abstract Background Short stature is associated with several disorders including wide variations of chromosomal disorders and single gene disorders. The objective of this report is to present the cytogenetic findings in Indonesian patients with short stature. Methods G-banding and interphase/metaphase FISH were performed on short stature patients with and without other clinical features who were referred by clinicians all over Indonesia to our laboratory during the year 2003–2009. Results The results of chromosomal analysis of ninety seven patients (mean age: 10.7 years old were collected. The group of patients with other clinical features showed sex chromosome abnormalities in 45% (18/40 and autosomal abnormalities in 10% (4/40, whereas those with short stature only, 42.1% (24/57 had sex chromosome abnormalities and 1.75% (1/57 had autosomal abnormalities. The autosomal chromosomal abnormalities involved mostly subtelomeric regions. Results discrepancies between karyotype and FISH were found in 10 patients, including detection of low-level monosomy X mosaicism in 6 patients with normal karyotype, and detection of mosaic aneuploidy chromosome 18 in 1 patient with 45,XX,rob(13;14(q10;q10. Statistical analysis showed no significant association between the groups and the type of chromosomal abnormalities. Conclusion Chromosome abnormalities account for about 50% of the short stature patients. Wide variations of both sex and autosomal chromosomes abnormalities were detected in the study. Since three out of five patients had autosomal structural abnormalities involving the subtelomeric regions, thus in the future, subtelomeric FISH or even a more sensitive method such as genomic/SNP microarray is needed to confirm deletions of subtelomeric regions of chromosome 9, 11 and 18. Low-level mosaicism in normal karyotype patients indicates interphase FISH need to be routinely carried out in short stature patients as an adjunct to karyotyping.

  20. The mating-type chromosome in the filamentous ascomycete Neurospora tetrasperma represents a model for early evolution of sex chromosomes.

    Directory of Open Access Journals (Sweden)

    Audrius Menkis

    2008-03-01

    Full Text Available We combined gene divergence data, classical genetics, and phylogenetics to study the evolution of the mating-type chromosome in the filamentous ascomycete Neurospora tetrasperma. In this species, a large non-recombining region of the mating-type chromosome is associated with a unique fungal life cycle where self-fertility is enforced by maintenance of a constant state of heterokaryosis. Sequence divergence between alleles of 35 genes from the two single mating-type component strains (i.e. the homokaryotic mat A or mat a-strains, derived from one N. tetrasperma heterokaryon (mat A+mat a, was analyzed. By this approach we were able to identify the boundaries and size of the non-recombining region, and reveal insight into the history of recombination cessation. The non-recombining region covers almost 7 Mbp, over 75% of the chromosome, and we hypothesize that the evolution of the mating-type chromosome in this lineage involved two successive events. The first event was contemporaneous with the split of N. tetrasperma from a common ancestor with its outcrossing relative N. crassa and suppressed recombination over at least 6.6 Mbp, and the second was confined to a smaller region in which recombination ceased more recently. In spite of the early origin of the first "evolutionary stratum", genealogies of five genes from strains belonging to an additional N. tetrasperma lineage indicate independent initiations of suppressed recombination in different phylogenetic lineages. This study highlights the shared features between the sex chromosomes found in the animal and plant kingdoms and the fungal mating-type chromosome, despite fungi having no separate sexes. As is often found in sex chromosomes of plants and animals, recombination suppression of the mating-type chromosome of N. tetrasperma involved more than one evolutionary event, covers the majority of the mating-type chromosome and is flanked by distal regions with obligate crossovers.

  1. A Novel Four-Way Complex Variant Translocation Involving Chromosome 46,XY,t(4;9;19;22)(q25:q34;p13.3;q11.2) in a Chronic Myeloid Leukemia Patient

    Science.gov (United States)

    Asif, Muhammad; Jamal, Mohammad Sarwar; Khan, Abdul Rehman; Naseer, Muhammad Imran; Hussain, Abrar; Choudhry, Hani; Malik, Arif; Khan, Shahida Aziz; Mahmoud, Maged Mostafa; Ali, Ashraf; Iram, Saima; Kamran, Kashif; Iqbal, Asim; Abduljaleel, Zainularifeen; Pushparaj, Peter Natesan; Rasool, Mahmood

    2016-01-01

    Philadelphia (Ph) chromosome (9;22)(q34;q11) is well established in more than 90% of chronic myeloid leukemia (CML) patients, and the remaining 5–8% of CML patients show variant and complex translocations, with the involvement of third, fourth, or fifth chromosome other than 9;22. However, in very rare cases, the fourth chromosome is involved. Here, we found a novel case of four-way Ph+ chromosome translocation involving 46,XY,t(4;9;19;22)(q25:q34;p13.3;q11.2) with CML in the chronic phase. Complete blood cell count of the CML patient was carried out to obtain total leukocytes count, hemoglobin, and platelets. Fluorescence in situ hybridization technique was used for the identification of BCR–ABL fusion gene, and cytogenetic test for the confirmation of Ph (9;22)(q34;q11) and the mechanism of variant translocation in the bone marrow. The patient is successfully treated with a dose of 400 mg/day imatinib mesylate (Gleevec). We observed a significant decrease in white blood cell count of 11.7 × 109/L after 48-month follow-up. Patient started feeling better generally. There was a reduction in the swelling of the body, fatigue, and anxiety. PMID:27303656

  2. A Novel four-way complex variant translocation involving chromosome 46, XY, t(4;9; 19;22(q25:q34;p13.3;q11.2 in a chronic myeloid leukemia patient

    Directory of Open Access Journals (Sweden)

    Muhammad eAsif

    2016-05-01

    Full Text Available Philadelphia (Ph chromosome (9; 22(q34;q11 is well established in more than 90% of chronic myeloid leukemia (CML patients and the remaining 5-8% CML patients show variant and complex translocations, with the involvement of third, fourth or fifth chromosome other then 9;22. However, in very rare cases the fourth chromosome is involved. Here, we find a novel case of four way Ph+ chromosome translocation involving 46,XY, t(4;9;19;22(q25:q34;p13.3;q11.2 with CML in the chronic phase. Complete blood cell count of CML patient was carried out to obtain total leukocytes count, hemoglobin and platelets. Fluorescence In situ hybridization technique was used for the identification of BCR-ABL fusion gene and cryptogenic test for the confirmation of Ph (9; 22(q34;q11 and the mechanism of variant translocation in the bone marrow. The patient is successfully treated with Imatinib mesylate (Gleevec with 400mg/day dose. We observed a significant decrease in WBC count after 48 months follow up 11.7 x109/L. Patient started feeling better generally. There was a reduction in the swelling of the body, fatigue and anxiety.

  3. 20-Mb duplication of chromosome 9p in a girl with minimal physical findings and normal IQ: narrowing of the 9p duplication critical region to 6 Mb.

    Science.gov (United States)

    Bonaglia, Maria Clara; Giorda, Roberto; Carrozzo, Romeo; Roncoroni, Maria Elena; Grasso, Rita; Borgatti, Renato; Zuffardi, Orsetta

    2002-10-01

    We studied the case of a girl with a partial 9p duplication, dup(9)(p22.1 --> p13.1). Molecular cytogenetics studies defined the chromosome 9 rearrangement as a direct duplication of 20 Mb from D9S1213 to D9S52. Microsatellite analysis demonstrated the presence of a double dosage of the paternal alleles and demonstrated that the duplication occurred between sister chromatids. The patient's phenotype was almost normal, with a few minor anomalies (dolichocephaly, crowded teeth, high arched palate) and normal IQ. The breakpoint's location in this patient and previously reported cases suggest that the critical region for the 9p duplication syndrome lies within a 6-Mb portion of chromosome 9p22 between markers D9S267 and D9S1213.

  4. Local circuitry involving parvalbumin-positive basket cells in the CA2 region of the hippocampus.

    Science.gov (United States)

    Mercer, Audrey; Eastlake, Karen; Trigg, Hayley L; Thomson, Alex M

    2012-01-01

    There is a growing recognition that the CA2 region of the hippocampus has its own distinctive properties, inputs, and pathologies. The dendritic and axonal patterns of some interneurons in this region are also strikingly different from those described previously in CA1 and CA3. The local circuitry in this region, however, had yet to be studied in detail. Accordingly, using dual intracellular recordings and biocytin-filling, excitatory and inhibitory connections involving CA2 parvalbumin-positive basket cells were characterized for the first time. CA2 basket cells targeted neighboring pyramidal cells and received excitatory inputs from them. CA2 basket cells that resembled those in CA1 with a fast spiking behavior and dendritic tree confined to the region of origin received depressing excitatory postsynaptic potentials (EPSPs). In contrast, unlike CA1 basket cells but like CA1 Oriens-Lacunosum Moleculare (OLM) cells, the majority of CA2 basket cells had horizontally oriented dendrites in Stratum Oriens (SO), which extended into all three CA subfields, had an adapting firing pattern, presented a "sag" in their voltage responses to hyperpolarizing current injection, and received facilitating EPSPs. The expression of I(h) did not influence the EPSP time courses and paired pulse ratios (PPR). Estimates of the probability of release (p) for the depressing and facilitating EPSPs were correlated with the PPR. Connections with low probabilities of release had higher PPR. Quantal amplitude (q) for the facilitating connections was larger than q at depressing inputs onto fast spiking basket cells.

  5. The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16

    NARCIS (Netherlands)

    C.J. Ward (Christopher); B. Peral (Belén); J. Hughes (Jim); S. Thomas (Siep); V. Gamble (Vicki); A.B. MacCarthy (Angela); J. Sloane-Stanley (Jackie); P. Buckle (Peter); P. Kearney (Peter); D. Higgs (Douglas); C. Ratcliffe; P.C. Harris (Peter); J.H. Roelfsema (Jeroen); L. Spruit (Lia); J.J. Saris (Jasper); H.G. Dauwerse (Hans); D. Peters (Dorien); M.H. Breuning (Martijn); M.D. Nellist (Mark); P.T. Brook-Carter (Phillip); M.M. Maheshwar (Magitha); I. Cordeiro (Isabel); H. Santos (Heloisa); P. Cabral (Pedro); J. Sampson (Julian); L.A.J. Janssen (Bart); A.L.W. Hesseling-Janssen (Arjenne); A.M.W. van den Ouweland (Ans); H.J.F.M.M. Eussen (Bert); S. Verhoef; D. Lindhout (Dick); D.J.J. Halley (Dicky)

    1994-01-01

    textabstractAutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently results in renal fallure due to progressive cyst development. The major locus, PKD1, maps to 16p13.3. We identified a chromosome translocation associated with ADPKD that disrupts a gene (PBP

  6. Occurrence of differential meiotic associations and additional chromosomes in the embryo-sac mother cells of Allium roylei Stearn

    Indian Academy of Sciences (India)

    Geeta Sharma; Ravinder N. Gohil

    2011-04-01

    A small population of complex translocation heterozygote plants of Allium roylei from the Bani region of Jammu Province was studied for meiosis in the female track. This study resulted in identification of two variants, having embryo-sac mother cells (EMCs) with more than 16 chromosomes. EMCs of the remaining plants invariably had diploid $(2n = 16)$ chromosome complement. Female meiosis, in general, was found to be abnormal, with nearly 23% and 11% chromosomes associating as quadrivalents or trivalents at prophase I and at metaphase I, respectively. This was followed by irregular segregation of chromosomes at anaphase I. Amongst the variants; one had 38% EMCs with eight bivalents plus two small sized chromosomes. Their small size, dispensable nature and tendency to affect the pairing behaviour of normal complement are some of the features that latter chromosomes share with the B chromosomes. Seventeen to nineteen chromosomes were observed in 35% EMCs of other variant; the remaining cells had 16 chromosomes. Chromosomal behaviour in both kind of cells (euploid and aneuploid) was more or less similar. Unlike female meiocytes, male meiocytes analysed earlier of this strain always had 16 chromosomes which paired to form extremely complex associations involving 3–16 chromosomes. The most likely cause of this asynchrony with regards to number of chromosomes involved in multivalent formation seems to be interaction of genes controlling chiasma formation with the different physiological conditions of male and female meiocytes.

  7. The Thatcher illusion reveals orientation dependence in brain regions involved in processing facial expressions.

    Science.gov (United States)

    Psalta, Lilia; Young, Andrew W; Thompson, Peter; Andrews, Timothy J

    2014-01-01

    Although the processing of facial identity is known to be sensitive to the orientation of the face, it is less clear whether orientation sensitivity extends to the processing of facial expressions. To address this issue, we used functional MRI (fMRI) to measure the neural response to the Thatcher illusion. This illusion involves a local inversion of the eyes and mouth in a smiling face-when the face is upright, the inverted features make it appear grotesque, but when the face is inverted, the inversion is no longer apparent. Using an fMRI-adaptation paradigm, we found a release from adaptation in the superior temporal sulcus-a region directly linked to the processing of facial expressions-when the images were upright and they changed from a normal to a Thatcherized configuration. However, this release from adaptation was not evident when the faces were inverted. These results show that regions involved in processing facial expressions display a pronounced orientation sensitivity.

  8. A structural locus for coagulation factor XIIIA (F13A) is located distal to the HLA region on chromosome 6p in man.

    Science.gov (United States)

    Olaisen, B; Gedde-Dahl, T; Teisberg, P; Thorsby, E; Siverts, A; Jonassen, R; Wilhelmy, M C

    1985-01-01

    Linkage between the locus for coagulation factor XIIIA (F13A) and HLA-region genes has been revealed during a linkage study between F13A and approximately 40 other polymorphic marker genes. In males, the maximum lod score between F13A and HLA-region genes (HLA-A, -C, -B, -DR; C4A, -B; Bf; and/or C2) is 7.60 at theta 1 = .18. To GLO, the maximum lod score is 2.37 at theta 1 = .19; to PGM3, .22 at theta 1 = .35. Female data indicate a clear sex difference in recombination frequency between F13A and HLA. The present findings, in combination with earlier knowledge of PGM3/GLO/HLA localization and gene distances, show that F13A is distal to HLA on the short arm of chromosome 6 in man. It is thus likely that by including FXIIIA typing in linkage studies, the whole male 6p is within mapping distance of highly polymorphic, classical marker genes. Earlier findings that the Hageman factor gene (F12) is located in the same chromosomal region may indicate the presence of a coagulation factor gene cluster in this region.

  9. High-resolution genotyping of chromosome 8 in colon adenocarcinomas reveals recurrent break point but no gene mutation in the 8p21 region.

    Science.gov (United States)

    Mourra, Najat; Zeitoun, Guy; Portier, Guillaume; Blanche, Hélène; Tubacher, Emmanuel; Gressin, Laetitia; Flejou, Jean-François; Tiret, Emmanuel; Thomas, Gilles; Olschwang, Sylviane

    2008-06-01

    The prognosis of patients with colorectal cancer is largely determined by the tumor stage. In this respect, colorectal cancer with lymph node metastases has the worst prognosis. Accordingly, there is considerable clinical interest in understanding the genetic mechanisms underlying metastasis formation. The short arm of chromosome 8 is often lost in colorectal cancer and has been associated with the advanced stages. A common region of deletion has been identified in 8p21, and we investigate here the localization of the putative tumor suppressor gene. A series of 683 sporadic microsatellite stability colorectal tumor samples has been genotyped on 12 microsatellite loci encompassing the common deleted region. Allelic losses were identified in 50% of the cases and 10 break points have been evidenced between D8S1734 and D8S1810, reducing the region of interest to D8S1771-D8S131. Among the 21 genes mapped in this interval, 14 candidate genes have been retained for the sequencing analysis of 48 tumors with 8p allelic loss. No mutation was found, suggesting more complex mechanisms of inactivation or side effects of chromosome arm 8q duplication, which might be up-regulating oncogenes not located within the deleted region.

  10. Diversity of breakpoints of variant Philadelphia chromosomes in chronic myeloid leukemia in Brazilian patients

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    Maria de Lourdes Lopes Ferrari Chauffaille

    2015-02-01

    Full Text Available Background: Chronic myeloid leukemia is a myeloproliferative disorder characterized by the Philadelphia chromosome or t(9;22(q34.1;q11.2, resulting in the break-point cluster regionAbelson tyrosine kinase fusion gene, which encodes a constitutively active tyrosine kinase protein. The Philadelphia chromosome is detected by karyotyping in around 90% of chronic myeloid leukemia patients, but 5-10% may have variant types. Variant Philadelphia chromosomes are characterized by the involvement of another chromosome in addition to chromosome 9 or 22. It can be a simple type of variant when one other chromosome is involved, or complex, in which two or more chromosomes take part in the translocation. Few studies have reported the incidence of variant Philadelphia chromosomes or the breakpoints involved among Brazilian chronic myeloid leukemia patients. Objective: The aim of this report is to describe the diversity of the variant Philadelphia chromosomes found and highlight some interesting breakpoint candidates for further studies. Methods: the Cytogenetics Section Database was searched for all cases with diagnoses of chronic myeloid leukemia during a 12-year period and all the variant Philadelphia chromosomes were listed. Results: Fifty (5.17% cases out of 1071 Philadelphia-positive chronic myeloid leukemia were variants. The most frequently involved chromosome was 17, followed by chromosomes: 1, 20, 6, 11, 2, 10, 12 and 15. Conclusion: Among all the breakpoints seen in this survey, six had previously been described: 11p15, 14q32, 15q11.2, 16p13.1, 17p13 and 17q21. The fact that some regions get more fre- quently involved in such rare rearrangements calls attention to possible predisposition that should be further studied. Nevertheless, the pathological implication of these variants remains unclear.

  11. Genetic mapping of a locus for multiple ephiphyseal dysplasia (EDM2) to a region of chromosome 1 containing a type IX collagen gene

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, M.D.; Choi, HiChang; Warman, M.L.; Loughlin, J.A.; Wordsworth, P.; Sykes, B.C.; Irven, C.M.M.; Smith, M.; Wynne-Davies, R.; Lipson, M.H. [and others

    1994-10-01

    Multiple epiphyseal dysplasia (MED) is a dominantly inherited chondrodysplasia characterized by mild short stature and early-onset osteoarthrosis. Some forms of MED clinically resemble another chondrodysplasia phenotype, the mild form of pseudoachondroplasia (PSACH). On the basis of their clinical similarities as well as similar ultra-structural and biochemical features in cartilage from some patients, it has been proposed that MED and PSACH belong to a single bone-dysplasia family. Recently, both mild and severe PSACH as well as a form of MED have been linked to the same interval on chromosome 19, suggesting that they may be allelic disorders. Linkage studies with the chromosome 19 markers were carried out in a large family with MED and excluded the previously identified interval. Using this family, we have identified a MED locus on the short arm of chromosome 1, in a region containing the gene (COL9A2) that encodes the {alpha}2 chain of type IX collagen, a structural component of the cartilage extracellular matrix. 39 refs., 3 figs., 3 tabs.

  12. Multiple sex-associated regions and a putative sex chromosome in zebrafish revealed by RAD mapping and population genomics.

    Directory of Open Access Journals (Sweden)

    Jennifer L Anderson

    Full Text Available Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio, neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate, the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F(2 offspring of reciprocal crosses between Oregon *AB and Nadia (NA wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome.

  13. Multiple sex-associated regions and a putative sex chromosome in zebrafish revealed by RAD mapping and population genomics.

    Science.gov (United States)

    Anderson, Jennifer L; Rodríguez Marí, Adriana; Braasch, Ingo; Amores, Angel; Hohenlohe, Paul; Batzel, Peter; Postlethwait, John H

    2012-01-01

    Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio), neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate), the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F(2) offspring of reciprocal crosses between Oregon *AB and Nadia (NA) wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag) markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome.

  14. Arabidopsis PTD is required for type I crossover formation and affects recombination frequency in two different chromosomal regions.

    Science.gov (United States)

    Lu, Pingli; Wijeratne, Asela J; Wang, Zhengjia; Copenhaver, Gregory P; Ma, Hong

    2014-03-20

    In eukaryotes, crossovers together with sister chromatid cohesion maintain physical association between homologous chromosomes, ensuring accurate chromosome segregation during meiosis I and resulting in exchange of genetic information between homologues. The Arabidopsis PTD (Parting Dancers) gene affects the level of meiotic crossover formation, but its functional relationships with other core meiotic genes, such as AtSPO11-1, AtRAD51, and AtMSH4, are unclear; whether PTD has other functions in meiosis is also unknown. To further analyze PTD function and to test for epistatic relationships, we compared the meiotic chromosome behaviors of Atspo11-1 ptd and Atrad51 ptd double mutants with the relevant single mutants. The results suggest that PTD functions downstream of AtSPO11-1 and AtRAD51 in the meiotic recombination pathway. Furthermore, we found that meiotic defects in rck ptd and Atmsh4 ptd double mutants showed similar meiotic phenotypes to those of the relevant single mutants, providing genetic evidences for roles of PTD and RCK in the type I crossovers pathway. Moreover, we employed a pollen tetrad-based fluorescence method and found that the meiotic crossover frequencies in two genetic intervals were significantly reduced from 6.63% and 22.26% in wild-type to 1.14% and 6.36%, respectively, in the ptd-2 mutant. These results revealed new aspects of PTD function in meiotic crossover formation.

  15. Chromosome aberrations in human lymphocytes from the plateau region of the Bragg curve for a carbon-ion beam

    Science.gov (United States)

    Manti, L.; Durante, M.; Grossi, G.; Pugliese, M.; Scampoli, P.; Gialanella, G.

    2007-06-01

    Radiotherapy with high-energy carbon ion beams can be more advantageous compared to photons because of better physical dose distribution and higher biological efficiency in tumour cell sterilization. Despite enhanced normal tissue sparing, damage incurred by normal cells at the beam entrance is unavoidable and may affect the progeny of surviving cells in the form of inheritable cytogenetic alterations. Furthermore, the quality of the beam along the Bragg curve is modified by nuclear fragmentation of projectile and target nuclei in the body. We present an experimental approach based on the use of a polymethylmethacrylate (PMMA) phantom that allows the simultaneous exposure to a particle beam of several biological samples positioned at various depths along the beam path. The device was used to measure the biological effectiveness of a 60 MeV/amu carbon-ion beam at inducing chromosomal aberrations in G0-human peripheral blood lymphocytes. Chromosome spreads were obtained from prematurely condensed cells and all structural aberration types were scored in Fluorescence in situ Hybridization (FISH)-painted chromosomes 1 and 2. Our results show a marked increase with depth in the aberration frequency prior to the Bragg peak, which is consistent with a linear energy transfer (LET)-dependent increase in biological effectiveness.

  16. Brain regions involved in human movement perception: a quantitative voxel-based meta-analysis.

    Science.gov (United States)

    Grosbras, Marie-Hélène; Beaton, Susan; Eickhoff, Simon B

    2012-02-01

    Face, hands, and body movements are powerful signals essential for social interactions. In the last 2 decades, a large number of brain imaging studies have explored the neural correlates of the perception of these signals. Formal synthesis is crucially needed, however, to extract the key circuits involved in human motion perception across the variety of paradigms and stimuli that have been used. Here, we used the activation likelihood estimation (ALE) meta-analysis approach with random effect analysis. We performed meta-analyses on three classes of biological motion: movement of the whole body, hands, and face. Additional analyses of studies of static faces or body stimuli and sub-analyses grouping experiments as a function of their control stimuli or task employed allowed us to identify main effects of movements and forms perception, as well as effects of task demand. In addition to specific features, all conditions showed convergence in occipito-temporal and fronto-parietal regions, but with different peak location and extent. The conjunction of the three ALE maps revealed convergence in all categories in a region of the right posterior superior temporal sulcus as well as in a bilateral region at the junction between middle temporal and lateral occipital gyri. Activation in these regions was not a function of attentional demand and was significant also when controlling for non-specific motion perception. This quantitative synthesis points towards a special role for posterior superior temporal sulcus for integrating human movement percept, and supports a specific representation for body parts in middle temporal, fusiform, precentral, and parietal areas.

  17. Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice.

    Science.gov (United States)

    Liu, Chunhong; Morishima, Masae; Jiang, Xiaoling; Yu, Tao; Meng, Kai; Ray, Debjit; Pao, Annie; Ye, Ping; Parmacek, Michael S; Yu, Y Eugene

    2014-06-01

    Trisomy 21 (Down syndrome, DS) is the most common human genetic anomaly associated with heart defects. Based on evolutionary conservation, DS-associated heart defects have been modeled in mice. By generating and analyzing mouse mutants carrying different genomic rearrangements in human chromosome 21 (Hsa21) syntenic regions, we found the triplication of the Tiam1-Kcnj6 region on mouse chromosome 16 (Mmu16) resulted in DS-related cardiovascular abnormalities. In this study, we developed two tandem duplications spanning the Tiam1-Kcnj6 genomic region on Mmu16 using recombinase-mediated genome engineering, Dp(16)3Yey and Dp(16)4Yey, spanning the 2.1 Mb Tiam1-Il10rb and 3.7 Mb Ifnar1-Kcnj6 regions, respectively. We found that Dp(16)4Yey/+, but not Dp(16)3Yey/+, led to heart defects, suggesting the triplication of the Ifnar1-Kcnj6 region is sufficient to cause DS-associated heart defects. Our transcriptional analysis of Dp(16)4Yey/+ embryos showed that the Hsa21 gene orthologs located within the duplicated interval were expressed at the elevated levels, reflecting the consequences of the gene dosage alterations. Therefore, we have identified a 3.7 Mb genomic region, the smallest critical genomic region, for DS-associated heart defects, and our results should set the stage for the final step to establish the identities of the causal gene(s), whose elevated expression(s) directly underlie this major DS phenotype.

  18. Comprehensive gene-based association study of a chromosome 20 linked region implicates novel risk loci for depressive symptoms in psychotic illness.

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    T Bernard Bigdeli

    Full Text Available BACKGROUND: Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants. METHODS: We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N = 270 families, 1408 subjects. These SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Given a previous report of novel linkage with chromosome 20p using latent classes of psychotic illness in this sample, association analysis was also conducted for each of five factor-derived scores based on the Operational Criteria Checklist for Psychotic Illness (delusions, hallucinations, mania, depression, and negative symptoms. Tests of association were conducted using the PDTPHASE and QPDTPHASE packages of UNPHASED. Empirical estimates of gene-wise significance were obtained by adaptive permutation of a the smallest observed P-value and b the threshold-truncated product of P-values for each locus. RESULTS: While no single variant was significant after LD-corrected Bonferroni-correction, our gene-dropping analyses identified loci which exceeded empirical significance criteria for both gene-based tests. Namely, R3HDML and C20orf39 are significantly associated with depressive symptoms of schizophrenia (P(emp<2×10⁻⁵ based on the minimum P-value and truncated-product methods, respectively. CONCLUSIONS: Using a gene-based approach to family-based association, R3HDML and C20orf39 were found to be significantly associated with clinical dimensions of schizophrenia. These findings demonstrate the efficacy of gene-based analysis and support previous evidence that chromosome 20 may harbor schizophrenia susceptibility or modifier loci.

  19. A gene catalogue of the euchromatic male-specific region of the horse Y chromosome: comparison with human and other mammals.

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    Nandina Paria

    Full Text Available Studies of the Y chromosome in primates, rodents and carnivores provide compelling evidence that the male specific region of Y (MSY contains functional genes, many of which have specialized roles in spermatogenesis and male-fertility. Little similarity, however, has been found between the gene content and sequence of MSY in different species. This hinders the discovery of species-specific male fertility genes and limits our understanding about MSY evolution in mammals. Here, a detailed MSY gene catalogue was developed for the horse--an odd-toed ungulate. Using direct cDNA selection from horse testis, and sequence analysis of Y-specific BAC clones, 37 horse MSY genes/transcripts were identified. The genes were mapped to the MSY BAC contig map, characterized for copy number, analyzed for transcriptional profiles by RT-PCR, examined for the presence of ORFs, and compared to other mammalian orthologs. We demonstrate that the horse MSY harbors 20 X-degenerate genes with known orthologs in other eutherian species. The remaining 17 genes are acquired or novel and have so far been identified only in the horse or donkey Y chromosomes. Notably, 3 transcripts were found in the heterochromatic part of the Y. We show that despite substantial differences between the sequence, gene content and organization of horse and other mammalian Y chromosomes, the functions of MSY genes are predominantly related to testis and spermatogenesis. Altogether, 10 multicopy genes with testis-specific expression were identified in the horse MSY, and considered likely candidate genes for stallion fertility. The findings establish an important foundation for the study of Y-linked genetic factors governing fertility in stallions, and improve our knowledge about the evolutionary processes that have shaped Y chromosomes in different mammalian lineages.

  20. BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1

    Directory of Open Access Journals (Sweden)

    Estivill Xavier

    2009-12-01

    Full Text Available Abstract Background Microdeletion of the chromosome 22q11.2 region is the most common genetic aberration among patients with velocardiofacial syndrome (VCFS but a subset of subjects do not show alterations of this chromosome region. Methods We analyzed 18 patients with VCFS-like features by comparative genomic hybridisation (aCGH array and performed a face-to-face slide hybridization with two different arrays: a whole genome and a chromosome 22-specific BAC array. Putative rearrangements were confirmed by FISH and MLPA assays. Results One patient carried a combination of rearrangements on 1q21.1, consisting in a microduplication of 212 kb and a close microdeletion of 1.15 Mb, previously reported in patients with variable phenotypes, including mental retardation, congenital heart defects (CHD and schizophrenia. While 326 control samples were negative for both 1q21.1 rearrangements, one of 73 patients carried the same 212-kb microduplication, reciprocal to TAR microdeletion syndrome. Also, we detected four copy number variants (CNVs inherited from one parent (a 744-kb duplication on 10q11.22; a 160 kb duplication and deletion on 22q11.21 in two cases; and a gain of 140 kb on 22q13.2, not present in control subjects, raising the potential role of these CNVs in the VCFS-like phenotype. Conclusions Our results confirmed aCGH as a successful strategy in order to characterize additional submicroscopic aberrations in patients with VCF-like features that fail to show alterations in 22q11.2 region. We report a 212-kb microduplication on 1q21.1, detected in two patients, which may contribute to CHD.

  1. Conserved regions of ribonucleoprotein ribonuclease MRP are involved in interactions with its substrate.

    Science.gov (United States)

    Esakova, Olga; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S

    2013-08-01

    Ribonuclease (RNase) MRP is a ubiquitous and essential site-specific eukaryotic endoribonuclease involved in the metabolism of a wide range of RNA molecules. RNase MRP is a ribonucleoprotein with a large catalytic RNA moiety that is closely related to the RNA component of RNase P, and multiple proteins, most of which are shared with RNase P. Here, we report the results of an ultraviolet-cross-linking analysis of interactions between a photoreactive RNase MRP substrate and the Saccharomyces cerevisiae RNase MRP holoenzyme. The results show that the substrate interacts with phylogenetically conserved RNA elements universally found in all enzymes of the RNase P/MRP family, as well as with a phylogenetically conserved RNA region that is unique to RNase MRP, and demonstrate that four RNase MRP protein components, all shared with RNase P, interact with the substrate. Implications for the structural organization of RNase MRP and the roles of its components are discussed.

  2. Molecular cytogenetic characterization of a small, familial supernumerary ring chromosome 7 associated with mental retardation and an abnormal phenotype.

    Science.gov (United States)

    Tan-Sindhunata, G; Castedo, S; Leegte, B; Mulder, I; vd Veen, A Y; vd Hout, A H; Wiersma, T J; van Essen, A J

    2000-05-15

    A family is described in which a mother and two of her children were mosaic for a small supernumerary ring chromosome. As the origin of the ring chromosome could not be determined by routine cytogenetic studies, fluorescent in situ hybridization was performed, which indicated that the ring chromosome was derived from the pericentromeric region of chromosome 7. Further characterization with a YAC-probe showed the involvement of the proximal q-arm of chromosome 7. Both sibs had speech difficulties and were mildly mentally retarded whereas the mother's intelligence was at the lower end of the normal range. They all had an unusual face, characterized by a flat profile, short forehead, downslant of the palpebral fissures, high and broad nasal bridge, simply formed ears, and prognathia. This is the second report of a small supernumerary ring chromosome derived from the pericentromeric region of chromosome 7, and the described clinical phenotype differs from that delineated in the previous report.

  3. POF regulates the expression of genes on the fourth chromosome in Drosophila melanogaster by binding to nascent RNA.

    Science.gov (United States)

    Johansson, Anna-Mia; Stenberg, Per; Allgardsson, Anders; Larsson, Jan

    2012-06-01

    In Drosophila, two chromosome-wide compensatory systems have been characterized: the dosage compensation system that acts on the male X chromosome and the chromosome-specific regulation of genes located on the heterochromatic fourth chromosome. Dosage compensation in Drosophila is accomplished by hypertranscription of the single male X chromosome mediated by the male-specific lethal (MSL) complex. The mechanism of this compensation is suggested to involve enhanced transcriptional elongation mediated by the MSL complex, while the mechanism of compensation mediated by the painting of fourth (POF) protein on the fourth chromosome has remained elusive. Here, we show that POF binds to nascent RNA, and this binding is associated with increased transcription output from chromosome 4. We also show that genes located in heterochromatic regions spend less time in transition from the site of transcription to the nuclear envelope. These results provide useful insights into the means by which genes in heterochromatic regions can overcome the repressive influence of their hostile environment.

  4. A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes.

    Science.gov (United States)

    Rivella, S; Tamanini, F; Bione, S; Mancini, M; Herman, G; Chatterjee, A; Maestrini, E; Toniolo, D

    1995-08-10

    The transcriptional organization of the region of the mouse X chromosome between the G6pd and the Fln1 genes was studied in detail, and it was compared with the syntenic region of the human chromosome. A cosmid contig of 250 kb was constructed by screening mouse cosmid libraries with probes for human genes and with whole cosmids. Overlapping cosmids were aligned by comparing EcoRI and rare-cutter restriction enzyme digestions. The gene order and the orientation of transcription were determined by hybridization with fragments from the 5' and 3' moieties of each cDNA. Our work demonstrates that all of the new genes identified in human are present in the mouse. The size of the region, 250 kb, is also very similar, as are gene order and gene organization: the transcriptional organization in "domains" described in human is found to be identical in the mouse. The major difference detected is the much lower content in rare-cutter restriction sites, which is related to the lower G+C and CpG content of mouse DNA. The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization.

  5. A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes

    Energy Technology Data Exchange (ETDEWEB)

    Rivella, S.; Tamanini, F.; Bione, S.; Mancini, M. [Istituto de Genetica Biochinica ed Evoluzionistica, Pavia (Italy)] [and others

    1995-08-10

    The transcriptional organization of the region of the mouse X chromosome between the G6pd and the Fln1 genes was studied in detail, and it was compared with the syntenic region of the human chromosome. A cosmid contig of 250 kb was constructed by screening mouse cosmid libraries with probes for human genes and with whole cosmids. Overlapping cosmids were aligned by comparing EcoRI and rare-cutter restriction enzyme digestions. The gene order and the orientation of transcription were determined by hybridization with fragments from the 5{prime} and 3{prime} moieties of each cDNA. Our work demonstrates that all of the new genes identified in human are present in the mouse. The size of the region, 250 kb, is also very similar, as are gene order and gene organizations: the transcriptional organization in {open_quotes}domains{close_quotes} described in human is found to be identical in the mouse. The major difference detected is the much lower content in rare-cutter restriction sites, which is related to the lower G+C and CpG content of mouse DNA. The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization. 17 refs., 4 figs.

  6. Autosomal dominant familial spastic paraplegia: Reduction of the FSPI candidate region on chromosome 14q to 7 cM and locus heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Gispert, S.; Santos, N.; Auburger, G.; Damen, R.; Voit, T. [University Hospital, Duesseldorf (Germany); Schulz, J.; Klockgether, T. [University Hospital, Tuebingen (Germany); Orozco, G. [Hospital Lenin, Holguin (Cuba); Kreuz, F. [Technical Univ., Dresden (Netherlands); Weissenbach, J. [Unite de Genetique, Paris (France)

    1995-01-01

    Three large pedigrees of Germany descent with autosomal dominant {open_quotes}pure{close_quotes} familial spastic paraplegia (FSP) were characterized clinically and genetically. Haplotype and linkage analyses, with microsatellites covering the FSP region on chromosome 14q (locus FSP1), were performed. In pedigree W, we found a haplotype that cosegregates with the disease and observed three crossing-over events, reducing the FSP1 candidate region to 7 cM; in addition, the observation of apparent anticipation in this family suggests a trinucleotide repeat expansion as the mutation. In pedigree D and S, the gene locus could be excluded from the whole FSP1 region, confirming the locus heterogeneity of autosomal dominant FSP. 11 refs., 2 figs., 2 tabs.

  7. Origin and domestication of papaya Yh chromosome

    Science.gov (United States)

    Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XYh). The hermaphrodite-specific region of the Yh chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previo...

  8. Characterisation of the Nevoid basal cell carcinoma (Gorlin`s) syndrome (NBCCS) gene region on chromosome 9q22-q31

    Energy Technology Data Exchange (ETDEWEB)

    Morris, D.J.; Digweed, M.; Sperling, K. [Freie Universitaet, Berlin (Germany)] [and other

    1994-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited malignancy-associated disease of unknown etiology. The gene has been mapped to chromosome 9q22-q31 by us and other groups, using linkage analysis and loss of heterozygosity studies. Subsequent linkage and haplotype analyses from 133 meioses in NBCCS families has refined the position of the gene between D9S12 and D9S287. Since the gene for Fanconi`s Anaemia type C (FAAC) has been assigned to the same 9q region, we have performed linkage analysis between FACC and NBCCCS in NBCCS families. No recombination has been observed between NBCCS and FACC and maximum lod scores of 34.98 and 11.94 occur for both diseases at the markers D9S196/D9S197. Southern blot analysis using an FACC cDNA probe has revealed no detectable rearrangements in our NBCCS patients. We have established a YAC contig spanning the region from D9S12 to D9S176 and STS content mapping in 22 YACs has allowed the ordering of 12 loci in the region, including the xeroderma pigmentosum type A (XPAC) gene, as follows: D9S151/D9S12P1 - D9S12P2 - D9S197 - D9S196 - D9S280 - FACC - D9S287/XPAC - D9S180 - D9S6 - D9S176. Using the contig we have been able to eliminate the {alpha}1 type XV collagen gene and the markers D9S119 and D9S297 from the NBCCS candidate region. Twelve YACs have been used to screen a chromosome 9 cosmid library and more than 1000 cosmids from the region have been identified to be used for the construction of a cosmid contig. A selection of these cosmids will be used for the isolation of coding sequencing from the region.

  9. Forefoot pain involving the metatarsal region: differential diagnosis with MR imaging.

    Science.gov (United States)

    Ashman, C J; Klecker, R J; Yu, J S

    2001-01-01

    Many disorders produce discomfort in the metatarsal region of the forefoot. These disorders include traumatic lesions of the soft tissues and bones (eg, turf toe, plantar plate disruption, sesamoiditis, stress fracture, stress response), Freiberg infraction, infection, arthritis, tendon disorders (eg, tendinosis, tenosynovitis, tendon rupture), nonneoplastic soft-tissue masses (eg, ganglia, bursitis, granuloma, Morton neuroma), and, less frequently, soft-tissue and bone neoplasms. Prior to the advent of magnetic resonance (MR) imaging, many of these disorders were not diagnosed noninvasively, and radiologic involvement in the evaluation of affected patients was limited. However, MR imaging has proved useful in detecting the numerous soft-tissue and early bone and joint processes that occur in this portion of the foot but are not depicted or as well characterized with other imaging modalities. Frequently, MR imaging allows a specific diagnosis based on the location, signal intensity characteristics, and morphologic features of the abnormality. Consequently, MR imaging is increasingly being used to evaluate patients with forefoot complaints. Radiologists should be familiar with the differential diagnosis and MR imaging features of disorders that can produce discomfort in this region.

  10. Detection of Inter-chromosomal Stable Aberrations by Multiple Fluorescence In Situ Hybridization (mFISH) and Spectral Karyotyping (SKY) in Irradiated Mice.

    Science.gov (United States)

    Pathak, Rupak; Koturbash, Igor; Hauer-Jensen, Martin

    2017-01-11

    Ionizing radiation (IR) induces numerous stable and unstable chromosomal aberrations. Unstable aberrations, where chromosome morphology is substantially compromised, can easily be identified by conventional chromosome staining techniques. However, detection of stable aberrations, which involve exchange or translocation of genetic materials without considerable modification in the chromosome morphology, requires sophisticated chromosome painting techniques that rely on in situ hybridization of fluorescently labeled DNA probes, a chromosome painting technique popularly known as fluorescence in situ hybridization (FISH). FISH probes can be specific for whole chromosome/s or precise sub-region on chromosome/s. The method not only allows visualization of stable aberrations, but it can also allow detection of the chromosome/s or specific DNA sequence/s involved in a particular aberration formation. A variety of chromosome painting techniques are available in cytogenetics; here two highly sensitive methods, multiple fluorescence in situ hybridization (mFISH) and spectral karyotyping (SKY), are discussed to identify inter-chromosomal stable aberrations that form in the bone marrow cells of mice after exposure to total body irradiation. Although both techniques rely on fluorescent labeled DNA probes, the method of detection and the process of image acquisition of the fluorescent signals are different. These two techniques have been used in various research areas, such as radiation biology, cancer cytogenetics, retrospective radiation biodosimetry, clinical cytogenetics, evolutionary cytogenetics, and comparative cytogenetics.

  11. High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.

    Science.gov (United States)

    Strom, S P; Stone, J L; Ten Bosch, J R; Merriman, B; Cantor, R M; Geschwind, D H; Nelson, S F

    2010-10-01

    Chromosome 17q11-q21 is a region of the genome likely to harbor susceptibility to autism (MIM(209850)) based on earlier evidence of linkage to the disorder. This linkage is specific to multiplex pedigrees containing only male probands (MO) within the Autism Genetic Resource Exchange (AGRE). Earlier, Stone et al.(1) completed a high-density single nucleotide polymorphism association study of 13.7 Mb within this interval, but common variant association was not sufficient to account for the linkage signal. Here, we extend this single nucleotide polymorphism-based association study to complete the coverage of the two-LOD support interval around the chromosome 17q linkage peak by testing the majority of common alleles in 284 MO trios. Markers within an interval containing the gene, CACNA1G, were found to be associated with Autism Spectrum Disorder at a locally significant level (P=1.9 × 10(-5)). While establishing CACNA1G as a novel candidate gene for autism, these alleles do not contribute a sufficient genetic effect to explain the observed linkage, indicating that there is substantial genetic heterogeneity despite the clear linkage signal. The region thus likely harbors a combination of multiple common and rare alleles contributing to the genetic risk. These data, along with earlier studies of chromosomes 5 and 7q3, suggest few if any major common risk alleles account for Autism Spectrum Disorder risk under major linkage peaks in the AGRE sample. This provides important evidence for strategies to identify Autism Spectrum Disorder genes, suggesting that they should focus on identifying rare variants and common variants of small effect.

  12. Chromosome 7q Region Associated with Female Rheumatoid Arthritis in a British Population Fails to Replicate in a North American Case-Control Series

    Science.gov (United States)

    Korman, Benjamin D; Seldin, Michael F; Taylor, Kimberly E; Le, Julie M; Lee, Annette T; Plenge, Robert M; Amos, Christopher I; Criswell, Lindsey A; Gregersen, Peter K; Kastner, Daniel L; Remmers, Elaine F

    2009-01-01

    Objective The single nucleotide polymorphism (SNP) rs11761231 on chromosome 7q has been reported as a sexually dimorphic marker for rheumatoid arthritis susceptibility in a British population. We sought to replicate this finding and better characterize susceptibility alleles in the region in a North American population. Methods DNA from two North American collections of RA patients and controls (1605 cases and 2640 controls) was genotyped for rs11761231 and 16 additional chromosome 7q tag SNPs using Sequenom iPlex assays. Association tests were performed for each collection and also separately contrasting male cases versus male controls and female cases versus female controls. Principal components analysis (EIGENSTRAT) was used to determine association with RA before and after adjusting for population stratification in the subset of the samples (772 cases and 1213 controls) with whole genome SNP data. Results We failed to replicate association of the 7q region with rheumatoid arthritis. Initially, rs11761231 showed evidence for association with RA in the NARAC collection (p=0.0076) and rs11765576 showed association with RA in both the NARAC (p = 0.019) and RA replication (p = 0.0013) collections. These markers also exhibited sexual differentiation. However, in the whole genome subset, neither SNP showed significant association with RA after correction for population stratification. Conclusion While two SNPs on chromosome 7q appeared to be associated with RA in a North American cohort, the significance of this finding did not withstand correction for population substructure. Our results emphasize the need to carefully account for population structure to avoid false positive disease associations. PMID:19116934

  13. Genomic analysis of a 1 Mb region near the telomere of Hessian fly chromosome X2 and avirulence gene vH13

    Directory of Open Access Journals (Sweden)

    Chen Ming-Shun

    2006-01-01

    Full Text Available Abstract Background To have an insight into the Mayetiola destructor (Hessian fly genome, we performed an in silico comparative genomic analysis utilizing genetic mapping, genomic sequence and EST sequence data along with data available from public databases. Results Chromosome walking and FISH were utilized to identify a contig of 50 BAC clones near the telomere of the short arm of Hessian fly chromosome X2 and near the avirulence gene vH13. These clones enabled us to correlate physical and genetic distance in this region of the Hessian fly genome. Sequence data from these BAC ends encompassing a 760 kb region, and a fully sequenced and assembled 42.6 kb BAC clone, was utilized to perform a comparative genomic study. In silico gene prediction combined with BLAST analyses was used to determine putative orthology to the sequenced dipteran genomes of the fruit fly, Drosophila melanogaster, and the malaria mosquito, Anopheles gambiae, and to infer evolutionary relationships. Conclusion This initial effort enables us to advance our understanding of the structure, composition and evolution of the genome of this important agricultural pest and is an invaluable tool for a whole genome sequencing effort.

  14. Genes involved in complex adaptive processes tend to have highly conserved upstream regions in mammalian genomes

    Directory of Open Access Journals (Sweden)

    Kohane Isaac

    2005-11-01

    Full Text Available Abstract Background Recent advances in genome sequencing suggest a remarkable conservation in gene content of mammalian organisms. The similarity in gene repertoire present in different organisms has increased interest in studying regulatory mechanisms of gene expression aimed at elucidating the differences in phenotypes. In particular, a proximal promoter region contains a large number of regulatory elements that control the expression of its downstream gene. Although many studies have focused on identification of these elements, a broader picture on the complexity of transcriptional regulation of different biological processes has not been addressed in mammals. The regulatory complexity may strongly correlate with gene function, as different evolutionary forces must act on the regulatory systems under different biological conditions. We investigate this hypothesis by comparing the conservation of promoters upstream of genes classified in different functional categories. Results By conducting a rank correlation analysis between functional annotation and upstream sequence alignment scores obtained by human-mouse and human-dog comparison, we found a significantly greater conservation of the upstream sequence of genes involved in development, cell communication, neural functions and signaling processes than those involved in more basic processes shared with unicellular organisms such as metabolism and ribosomal function. This observation persists after controlling for G+C content. Considering conservation as a functional signature, we hypothesize a higher density of cis-regulatory elements upstream of genes participating in complex and adaptive processes. Conclusion We identified a class of functions that are associated with either high or low promoter conservation in mammals. We detected a significant tendency that points to complex and adaptive processes were associated with higher promoter conservation, despite the fact that they have emerged

  15. A genomic region involved in the formation of adhesin fibers in Bacillus cereus biofilms

    Directory of Open Access Journals (Sweden)

    Joaquín eCaro-Astorga

    2015-01-01

    Full Text Available Bacillus cereus is a bacterial pathogen that is responsible for many recurrent disease outbreaks due to food contamination. Spores and biofilms are considered the most important reservoirs of B. cereus in contaminated fresh vegetables and fruits. Biofilms are bacterial communities that are difficult to eradicate from biotic and abiotic surfaces because of their stable and extremely strong extracellular matrix. These extracellular matrixes contain exopolysaccharides, proteins, extracellular DNA, and other minor components. Although B. cereus can form biofilms, the bacterial features governing assembly of the protective extracellular matrix are not known. Using the well-studied bacterium B. subtilis as a model, we identified two genomic loci in B. cereus, which encodes two orthologs of the amyloid-like protein TasA of B. subtilis and a SipW signal peptidase. Deletion of this genomic region in B. cereus inhibited biofilm assembly; notably, mutation of the putative signal peptidase SipW caused the same phenotype. However, mutations in tasA or calY did not completely prevent biofilm formation; strains that were mutated for either of these genes formed phenotypically different surface attached biofilms. Electron microscopy studies revealed that TasA polymerizes to form long and abundant fibers on cell surfaces, whereas CalY does not aggregate similarly. Heterologous expression of this amyloid-like cassette in a B. subtilis strain lacking the factors required for the assembly of TasA amyloid-like fibers revealed i the involvement of this B. cereus genomic region in formation of the air-liquid interphase pellicles and ii the intrinsic ability of TasA to form fibers similar to the amyloid-like fibers produced by its B. subtilis ortholog.

  16. Interspecific Y chromosome variation is sufficient to rescue hybrid male sterility and is influenced by the grandparental origin of the chromosomes.

    Science.gov (United States)

    Araripe, L O; Tao, Y; Lemos, B

    2016-06-01

    Y chromosomes display population variation within and between species. Co-evolution within populations is expected to produce adaptive interactions between Y chromosomes and the rest of the genome. One consequence is that Y chromosomes from disparate populations could disrupt harmonious interactions between co-evolved genetic elements and result in reduced male fertility, sterility or inviability. Here we address the contribution of 'heterospecific Y chromosomes' to fertility in hybrid males carrying a homozygous region of Drosophila mauritiana introgressed in the Drosophila simulans background. In order to detect Y chromosome-autosome interactions, which may go unnoticed in a single-species background of autosomes, we constructed hybrid genotypes involving three sister species: Drosophila simulans, D. mauritiana, and D. sechellia. These engineered strains varied due to: (i) species origin of the Y chromosome (D. simulans or D. sechellia); (ii) location of the introgressed D. mauritiana segment on the D. simulans third chromosome, and (iii) grandparental genomic background (three genotypes of D. simulans). We find complex interactions between the species origin of the Y chromosome, the identity of the D. mauritiana segment and the grandparental genetic background donating the chromosomes. Unexpectedly, the interaction of the Y chromosome and one segment of D. mauritiana drastically reduced fertility in the presence of Ysim, whereas the fertility is partially rescued by the Y chromosome of D. sechellia when it descends from a specific grandparental genotype. The restoration of fertility occurs in spite of an autosomal and X-linked genome that is mostly of D. simulans origin. These results illustrate the multifactorial basis of genetic interactions involving the Y chromosome. Our study supports the hypothesis that the Y chromosome can contribute significantly to the evolution of reproductive isolation and highlights the conditional manifestation of infertility in

  17. Ocular expression and distribution of products of the POAG-associated chromosome 9p21 gene region.

    Directory of Open Access Journals (Sweden)

    Glyn Chidlow

    Full Text Available It has recently been shown that there are highly significant associations for common single nucleotide polymorphisms (SNPs near the CDKN2B-AS1 gene region at the 9p21 locus with primary open angle glaucoma (POAG, a leading cause of irreversible blindness. This gene region houses the CDKN2B/p15(INK4B , CDKN2A/p16(INK4A and p14ARF (rat equivalent, p19(ARF tumour suppressor genes and is adjacent to the S-methyl-5'-thioadenosine phosphorylase (MTAP gene. In order to understand the ocular function of these genes and, therefore, how they may be involved in the pathogenesis of POAG, we studied the distribution patterns of each of their products within human and rat ocular tissues. MTAP mRNA was detected in the rat retina and optic nerve and its protein product was localised to the corneal epithelium, trabecular meshwork and retinal glial cells in both human and rat eyes. There was a very low level of p16(INK4A mRNA present within the rat retina and slightly more in the optic nerve, although no protein product could be detected in either rat or human eyes with any of the antibodies tested. P19(ARF mRNA was likewise only present at very low levels in rat retina and slightly higher levels in the optic nerve. However, no unambiguous evidence was found to indicate expression of specific P19(ARF/p14(ARF proteins in either rat or human eyes, respectively. In contrast, p15(INK4B mRNA was detected in much higher amounts in both retina and optic nerve compared with the other genes under analysis. Moreover, p15(INK4B protein was clearly localised to the retinal inner nuclear and ganglion cell layers and the corneal epithelium and trabecular meshwork in rat and human eyes. The presented data provide the basis for future studies that can explore the roles that these gene products may play in the pathogenesis of glaucoma and other models of optic nerve damage.

  18. Chromosomal mosaicism goes global

    Directory of Open Access Journals (Sweden)

    Yurov Yuri B

    2008-11-01

    Full Text Available Intercellular differences of chromosomal content in the same individual are defined as chromosomal mosaicism (alias intercellular or somatic genomic variations or, in a number of publications, mosaic aneuploidy. It has long been suggested that this phenomenon poorly contributes both to intercellular (interindividual diversity and to human disease. However, our views have recently become to change due to a series of communications demonstrated a higher incidence of chromosomal mosaicism in diseased individuals (major psychiatric disorders and autoimmune diseases as well as depicted chromosomal mosaicism contribution to genetic diversity, the central nervous system development, and aging. The later has been produced by significant achievements in the field of molecular cytogenetics. Recently, Molecular Cytogenetics has published an article by Maj Hulten and colleagues that has provided evidences for chromosomal mosaicism to underlie formation of germline aneuploidy in human female gametes using trisomy 21 (Down syndrome as a model. Since meiotic aneuploidy is suggested to be the leading genetic cause of human prenatal mortality and postnatal morbidity, these data together with previous findings define chromosomal mosaicism not as a casual finding during cytogenetic analyses but as a more significant biological phenomenon than previously recognized. Finally, the significance of chromosomal mosaicism can be drawn from the fact, that this phenomenon is involved in genetic diversity, normal and abnormal prenatal development, human diseases, aging, and meiotic aneuploidy, the intrinsic cause of which remains, as yet, unknown.

  19. Numerically abnormal chromosome constitutions in humans

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  20. Brain regions involved in swallowing: Evidence from stroke patients in a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Shiva Ebrahimian Dehaghani

    2016-01-01

    Full Text Available Background: Limited data available about the mechanisms of dysphagia and areas involving swallow after brain damage; accordingly it is hard to predict which cases are more likely to develop swallowing dysfunction based on the neuroimaging. The aim of this study was to investigate the relationship between brain lesions and dysphagia in a sample of acute conscious stroke patients.Materials and Methods: In a cross-sectional study, 113 acute conscious stroke patients (69 male mean [standard deviation (SD] age 64.37 [15.1], participated in this study. Two neurologists and one radiologist localized brain lesions according to neuroimaging of the patients. Swallowing functions were assessed clinically by an expert speech pathologist with the Mann Assessment of Swallowing Ability (MASA. The association of brain region and swallowing problem was statistically evaluated using Chi-square test. Results: Mean (SD MASA score for the dysphagic patients was 139.61 (29.77. Swallowing problem was significantly more prevalent in the right primary sensory (P = 0.03, right insula (P = 0.005, and right internal capsule (P = 0.05. Conclusion: It may be concluded from these findings that the right hemisphere lesions associated with occurring dysphagia. Further studies using more advanced diagnostic tools on big samples particularly in a perspective structure are needed.

  1. System Model Bias Processing Approach for Regional Coordinated States Information Involved Filtering

    Directory of Open Access Journals (Sweden)

    Zebo Zhou

    2016-01-01

    Full Text Available In the Kalman filtering applications, the conventional dynamic model which connects the states information of two consecutive epochs by state transition matrix is usually predefined and assumed to be invariant. Aiming to improve the adaptability and accuracy of dynamic model, we propose multiple historical states involved filtering algorithm. An autoregressive model is used as the dynamic model which is subsequently combined with observation model for deriving the optimal window-recursive filter formulae in the sense of minimum mean square error principle. The corresponding test statistics characteristics of system residuals are discussed in details. The test statistics of regional predicted residuals are then constructed in a time-window for model bias testing with two hypotheses, that is, the null and alternative hypotheses. Based on the innovations test statistics, we develop a model bias processing procedure including bias detection, location identification, and state correction. Finally, the minimum detectable bias and bias-to-noise ratio are both computed for evaluating the internal and external reliability of overall system, respectively.

  2. PprA Protein Is Involved in Chromosome Segregation via Its Physical and Functional Interaction with DNA Gyrase in Irradiated Deinococcus radiodurans Bacteria.

    Science.gov (United States)

    Devigne, Alice; Guérin, Philippe; Lisboa, Johnny; Quevillon-Cheruel, Sophie; Armengaud, Jean; Sommer, Suzanne; Bouthier de la Tour, Claire; Servant, Pascale

    2016-01-01

    PprA, a radiation-induced Deinococcus-specific protein, was previously shown to be required for cell survival and accurate chromosome segregation after exposure to ionizing radiation. Here, we used an in vivo approach to determine, by shotgun proteomics, putative PprA partners coimmunoprecipitating with PprA when cells were exposed to gamma rays. Among them, we found the two subunits of DNA gyrase and, thus, chose to focus our work on characterizing the activities of the deinococcal DNA gyrase in the presence or absence of PprA. Loss of PprA rendered cells hypersensitive to novobiocin, an inhibitor of the B subunit of DNA gyrase. We showed that treatment of bacteria with novobiocin resulted in induction of the radiation desiccation response (RDR) regulon and in defects in chromosome segregation that were aggravated by the absence of PprA. In vitro, the deinococcal DNA gyrase, like other bacterial DNA gyrases, possesses DNA negative supercoiling and decatenation activities. These two activities are inhibited in vitro by novobiocin and nalidixic acid, whereas PprA specifically stimulates the decatenation activity of DNA gyrase. Together, these results suggest that PprA plays a major role in chromosome decatenation via its interaction with the deinococcal DNA gyrase when D. radiodurans cells are recovering from exposure to ionizing radiation. IMPORTANCE D. radiodurans is one of the most radiation-resistant organisms known. This bacterium is able to cope with high levels of DNA lesions generated by exposure to extreme doses of ionizing radiation and to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Here, we identified partners of PprA, a radiation-induced Deinococcus-specific protein, previously shown to be required for radioresistance. Our study leads to three main findings: (i) PprA interacts with DNA gyrase after irradiation, (ii) treatment of cells with novobiocin results in defects in chromosome segregation that are

  3. Genomic insights into hybridization in a localized region of sympatr y between pewee sister species (Contopus sordidulus × C. virens) and their chromosomal patterns of differentiation

    Institute of Scientific and Technical Information of China (English)

    Joseph D Manthey; and Mark B Robbins

    2016-01-01

    Background: The Great Plains of the United States includes a large number of hybrid and contact zones between bird species. The amount of gene lfow between sister species in these zones ranges from very rare hybridization events to widespread and prevalent introgression. Some of these avian systems have been studied extensively, while others have been indeterminate of whether hybridization exists in areas of sympatry. Using genomic-level approaches allows investigation of genomic patterns of hybridization and gene lfow between species—or lack thereof. Methods: We investigated a narrow zone of sympatry in Nebraska, USA between pewee species (Contopus sordidu-lus and C. virens), for which no hybridization has been conifrmed. We used thousands of single nucleotide polymor-phisms to identify potential hybridization and investigate genomic patterns of differentiation between these two species. Results: We found evidence of multiple hybrid individuals in the contact zone. Little genomic variation was ifxed between species, but a large proportion had differentiated allele frequencies between species. There was a positive relationship between genetic differentiation and chromosome size. Conclusions: We provided the ifrst conclusive evidence of hybridization between C. sordidulus and C. virens, in a region where secondary contact likely occurred due to human disturbance and habitat modiifcation. The genomic patterns of differentiation affrm that these species split in the relatively recent past. Finally, the relationship of chro-mosome size and genetic differentiation may have resulted from differential rates of chromosomal recombination in songbirds and genetic differentiation between species largely due to genetic drift (possibly in concert with selection).

  4. Mechanisms of telomere loss and their consequences for chromosome instability

    Directory of Open Access Journals (Sweden)

    Keiko eMuraki

    2012-10-01

    Full Text Available The ends of chromosomes in mammals, called telomeres, are composed of a 6 base pair repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

  5. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    DEFF Research Database (Denmark)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may pl...

  6. Chromosomal localization of mitochondrial transcription factor A (TCF6), single-stranded DNA-binding protein (SSBP), and endonuclease G (ENDOG), three human housekeeping genes involving in mitochondrial biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tiranti, V.; Rossi, G.; DiDonato, S. [Istituto Nazionale Neurologico, Carlo Besta (Italy)] [and others

    1995-01-20

    By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci of mitochondrial single-stranded DNA-binding protein (SSBP), mitochondrial transcription factor A (TCF6), and mitochondrial endonuclease G (ENDOG) genes to human chromosomes 7q34, 10q21, and 9q34.1, respectively. The products of these three genes are involved in fundamental aspects of mitochondrial biogenesis, such as replication and transcription of the mitochondrial genome. The chromosomal localization of these genes is important to testing whether the corresponding proteins may play a role in the etiopathogenesis of human disorders associated with qualitative or quantitative abnormalities of mitochondrial DNA. 20 refs., 1 fig., 2 tabs.

  7. Modeling Chromosomes

    Science.gov (United States)

    Robertson, Carol

    2016-01-01

    Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…

  8. Cloning and characterization of a novel gene (C17orf25) from the deletion region on chromosome 17p13.3 in hepatocelular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Using a combination of hybridization of PAC to a cDNA library and RACE technique, we isolated a novel cDNA, designated as C17orf25 (Chromosome 17 open reading frame 25, previously named it HC71A), from the deletion region on chromosome 17p13.3. The cDNA encodes a protein of 313 amino acids with a calculated molecular mass of 34.8 kDa. C17orf25 is divided into 10 exons and 9 introns, spanning 23 kb of genomic DNA. Northern blot analysis showed that the mRNA expression of C17orf25 was decreased in hepatocellular carcinoma samples as compared to adjacent noncancerous liver tissues from the same patients. The transfection of C17orf25 into the hepatocellular carcinoma cell SMMC7721 and overexpression could inhibit the cell growth. The above results indicate that C17orf25 is a novel human gene, and the cloning and preliminary characterization of C17orf25 is a prerequisite for further functional analysis of this novel gene in human hepatocellular carcinoma.

  9. CHARACTERIZATION AND CHROMOSOMAL ASSIGNMENT OF YEAST ARTIFICIAL CHROMOSOMES CONTAINING HUMAN 3P13-P21-SPECIFIC SEQUENCE-TAGGED SITES

    NARCIS (Netherlands)

    MICHAELIS, SC; BARDENHEUER, W; LUX, A; SCHRAMM, A; GOCKEL, A; SIEBERT, R; WILLERS, C; SCHMIDTKE, K; TODT, B; VANDERHOUT, AH; BUYS, CHCM; HEPPELLPARTON, AC; RABBITTS, PH; UNGAR, S; SMITH, D; LEPASLIER, D; COHEN, D; OPALKA, B; SCHUTTE, J

    1995-01-01

    Human chromosomal region 3p12-p23 is proposed to harbor at least three tumor suppressor genes involved in the development of lung cancer, renal cell carcinoma, and other neoplasias. In order to identify one of these genes we defined sequence tagged sites (STSs) specific for 3p13-p24.2 by analyzing a

  10. Structural organization of the inactive X chromosome in the mouse.

    Science.gov (United States)

    Giorgetti, Luca; Lajoie, Bryan R; Carter, Ava C; Attia, Mikael; Zhan, Ye; Xu, Jin; Chen, Chong Jian; Kaplan, Noam; Chang, Howard Y; Heard, Edith; Dekker, Job

    2016-07-28

    X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD

  11. Linkage and association analyses identify a candidate region for apoB level on chromosome 4q32.3 in FCHL families.

    Science.gov (United States)

    Wijsman, Ellen M; Rothstein, Joseph H; Igo, Robert P; Brunzell, John D; Motulsky, Arno G; Jarvik, Gail P

    2010-06-01

    Familial combined hyperlipidemia (FCHL) is a complex trait leading to cardiovascular disease (CVD) risk. Elevated levels and size of apolipoprotein B (apoB) and low-density lipoprotein (LDL) are associated with FCHL, which is genetically heterogeneous and is likely caused by rare variants. We carried out a linkage-based genome scan of four large FCHL pedigrees for apoB level that is independent of LDL: apoB level that is adjusted for LDL level and size. Follow-up included SNP genotyping in the region with the strongest evidence of linkage. Several regions with the evidence of linkage in individual pedigrees support the rare variant model. Evidence of linkage was strongest on chromosome 4q, with multipoint analysis in one pedigree giving LOD = 3.1 with a parametric model, and a log Bayes Factor = 1.5 from a Bayesian oligogenic approach. Of the 293 SNPs spanning the implicated region on 4q, rs6829588 completely explained the evidence of linkage. This SNP accounted for 39% of the apoB phenotypic variance, with heterozygotes for this SNP having a trait value that was approximately 30% higher than that of the high-frequency homozygote, thus identifying and considerably refining a strong candidate region. These results illustrate the advantage of using large pedigrees in the search for rare variants: reduced genetic heterogeneity within single pedigrees coupled with the large number of individuals segregating otherwise-rare single variants leads to high power to implicate such variants.

  12. Paternal uniparental disomy chromosome 14-like syndrome due a maternal de novo 160 kb deletion at the 14q32.2 region not encompassing the IG- and the MEG3-DMRs: Patient report and genotype-phenotype correlation.

    Science.gov (United States)

    Corsello, Giovanni; Salzano, Emanuela; Vecchio, Davide; Antona, Vincenzo; Grasso, Marina; Malacarne, Michela; Carella, Massimo; Palumbo, Pietro; Piro, Ettore; Giuffrè, Mario

    2015-12-01

    The human chromosome 14q32 carries a cluster of imprinted genes which include the paternally expressed genes (PEGs) DLK1 and RTL1, as well as the maternally expressed genes (MEGs) MEG3, RTL1as, and MEG8. PEGs and MEGs expression at the 14q32.2-imprinted region are regulated by two differentially methylated regions (DMRs): the IG-DMR and the MEG3-DMR, which are respectively methylated on the paternal and unmethylated on the maternal chromosome 14 in most cells. Genetic and epigenetic abnormalities affecting these imprinted gene clusters result in two different phenotypes currently known as maternal upd(14) syndrome and paternal upd(14) syndrome. However, only few patients carrying a maternal deletion at the 14q32.2-imprinted critical region have been reported so far. Here we report on the first patient with a maternal de novo deletion of 160 kb at the 14q32.2 chromosome that does not involves the IG-DMR or the MEG3-DMR but elicits a full upd(14)pat syndrome's phenotype encompassing the three mentioned MEGs. By the analysis of this unique genotype-phenotype correlation, we further widen the spectrum of the congenital anomalies associated to this rare disorder and we propose that the paternally expressed imprinted RTL1 gene, as well as its maternally expressed RTL1as antisense transcript, may play a prominent causative role.

  13. Genetic and physical mapping of the Treacher Collins syndrome locus with respect to loci in the chromosome 5q3 region

    Energy Technology Data Exchange (ETDEWEB)

    Jabs, E.W.; Li, Xiang; Coss, C.; Taylor, E. (Johns Hopkins School of Medicine, Baltimore, MD (United States)); Lovett, M. (Univ. of Texas Southwestern Medical Center, San Antonio, TX (United States)); Yamaoka, L.H.; Speer, M.C. (Duke Univ. Medical Center, Durham, NC (United States)); Cadle, R.; Hall, B. (Univ. of Kentucky, Lexington, KY (United States)); Brown, K. (Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY (United States)) (and others)

    1993-10-01

    Treacher Collins syndrome is an autosomal dominant, craniofacial developmental disorder, and its locus (TCOF1) has been mapped to chromosome 5q3. To refine the location of the gene within this region, linkage analysis was performed among the TCOF1 locus and 12 loci (IL9, FGFA, GRL, D5S207, D5S210, D5S376, CSF1R, SPARC, D5S119, D5S209, D5S527, FGFR4) in 13 Treacher Collins syndrome families. The highest maximum lod score was obtained between loci TCOF1 and D5S210 (Z = 10.52; [theta] = 0.02 [+-] 0.07). The best order, IL9-GRL-D5S207/D5S210-CSF1R-SPARC-D5S119, and genetic distances among these loci were determined in the 40 CEPH families by multipoint linkage analysis. YAC clones were used to establish the order of loci, centromere-5[prime]GRL3[prime]-D5S207-D5S210-D5S376-CSF1R-SPARC-D5S119-telomere. By combining known physical mapping data with ours, the order of chromosome 5q3 markers is centomere-IL9-FGFA-5[prime]GRL3[prime]-D5s207-D5S210-D5S376-CSF1R-SPARC-D5S119-D5S209-FGFR4-telomere. Based on this order, haplotype analysis suggests that the TCOF1 locus resides distal CSF1R and proximal to SPARC within a region less than 1 Mb in size. 29 refs., 2 figs., 2 tabs.

  14. Comparative genomic analysis of duplicated homoeologous regions involved in the resistance of Brassica napus to stem canker

    Directory of Open Access Journals (Sweden)

    Berline eFopa Fomeju

    2015-09-01

    Full Text Available All crop species are current or ancient polyploids. Following whole genome duplication, structural and functional modifications result in differential gene content or regulation in the duplicated regions, which can play a fundamental role in the diversification of genes underlying complex traits. We have investigated this issue in Brassica napus, a species with a highly duplicated genome, with the aim of studying the structural and functional organization of duplicated regions involved in quantitative resistance to stem canker, a disease caused by the fungal pathogen Leptosphaeria maculans. Genome-wide association analysis on two oilseed rape panels confirmed that duplicated regions of ancestral blocks E, J, R, U and W were involved in resistance to stem canker. The structural analysis of the duplicated genomic regions showed a higher gene density on the A genome than on the C genome and a better collinearity between homoeologous regions than paralogous regions, as overall in the whole B. napus genome. The three ancestral sub-genomes were involved in the resistance to stem canker and the fractionation profile of the duplicated regions corresponded to what was expected from results on the B. napus progenitors. About 60% of the genes identified in these duplicated regions were single-copy genes while less than 5% were retained in all the duplicated copies of a given ancestral block. Genes retained in several copies were mainly involved in response to stress, signaling or transcription regulation. Genes with resistance-associated markers were mainly retained in more than two copies. These results suggested that some genes underlying quantitative resistance to stem canker might be duplicated genes. Genes with a hydrolase activity that were retained in one copy or R-like genes might also account for resistance in some regions. Further analyses need to be conducted to indicate to what extent duplicated genes contribute to the expression of the

  15. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    2012-07-15

    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  16. Chromosome 11q13 deletion syndrome

    Science.gov (United States)

    Kim, Yu-Seon; Kim, Gun-Ha; Byeon, Jung Hye; Eun, So-Hee

    2016-01-01

    Chromosome 11q13 deletion syndrome has been previously reported as either otodental syndrome or oculo-oto-dental syndrome. The otodental syndrome is characterized by dental abnormalities and high-frequency sensorineural hearing loss, and by ocular coloboma in some cases. The underlying genetic defect causing otodental syndrome is a hemizygous microdeletion involving the FGF3 gene on chromosome 11q13.3. Recently, a new form of severe deafness, microtia (small ear) and small teeth, without the appearance of eye abnormalities, was also reported. In this report, we describe a 1-year-old girl presenting with ptosis of the left upper eyelid, right auricular deformity, high-arched palate, delayed dentition, simian line on the right hand, microcephaly, and developmental delay. In this patient, we identified a deletion in the chromosome 11q13.2-q13.3 (2.75 Mb) region by using an array-comparative genomic hybridization analysis. The deletion in chromosome 11q13 results in a syndrome characterized by variable clinical manifestations. Some of these manifestations involve craniofacial dysmorphology and require a functional workup for hearing, ophthalmic examinations, and long-term dental care. PMID:28018436

  17. The Chromosome 9p21 CVD- and T2D-Associated Regions in a Norwegian Population (The HUNT2 Survey

    Directory of Open Access Journals (Sweden)

    Øyvind Helgeland

    2015-01-01

    Full Text Available Background. Two adjacent regions upstream CDKN2B on chromosome 9p21 have been associated with type 2 diabetes (T2D and progression of cardiovascular disease (CVD. The precise location and number of risk variants have not been completely delineated and a possible synergistic relationship between the adjacent regions is not fully addressed. By a population based cross-sectional case-control design, we genotyped 18 SNPs upstream of CDKN2B tagging 138 kb in and around two LD-blocks associated with CVD and T2D and investigated associations with T2D, angina pectoris (AP, myocardial infarction (MI, coronary heart disease (CHD; AP or AMI, and stroke using 5,564 subjects from HUNT2. Results. Single point and haplotype analysis showed evidence for only one common T2D risk haplotype (rs10757282∣rs10811661: OR = 1.19, P=2.0×10-3 in the region. We confirmed the strong association between SNPs in the 60 kb CVD region with AP, MI, and CHD (P<0.01. Conditioning on the lead SNPs in the region, we observed two suggestive independent single SNP association signals for MI, rs2065501  (P=0.03 and rs3217986  (P=0.04. Conclusions. We confirmed the association of known variants within the 9p21 interval with T2D and CHD. Our results further suggest that additional CHD susceptibility variants exist in this region.

  18. Chromatin Folding, Fragile Sites, and Chromosome Aberrations Induced by Low- and High- LET Radiation

    Science.gov (United States)

    Zhang, Ye; Cox, Bradley; Asaithamby, Aroumougame; Chen, David J.; Wu, Honglu

    2013-01-01

    We previously demonstrated non-random distributions of breaks involved in chromosome aberrations induced by low- and high-LET radiation. To investigate the factors contributing to the break point distribution in radiation-induced chromosome aberrations, human epithelial cells were fixed in G1 phase. Interphase chromosomes were hybridized with a multicolor banding in situ hybridization (mBAND) probe for chromosome 3 which distinguishes six regions of the chromosome in separate colors. After the images were captured with a laser scanning confocal microscope, the 3-dimensional structure of interphase chromosome 3 was reconstructed at multimega base pair scale. Specific locations of the chromosome, in interphase, were also analyzed with bacterial artificial chromosome (BAC) probes. Both mBAND and BAC studies revealed non-random folding of chromatin in interphase, and suggested association of interphase chromatin folding to the radiation-induced chromosome aberration hotspots. We further investigated the distribution of genes, as well as the distribution of breaks found in tumor cells. Comparisons of these distributions to the radiation hotspots showed that some of the radiation hotspots coincide with the frequent breaks found in solid tumors and with the fragile sites for other environmental toxins. Our results suggest that multiple factors, including the chromatin structure and the gene distribution, can contribute to radiation-induced chromosome aberrations.

  19. Chromosomes in the genesis and progression of ependymomas

    DEFF Research Database (Denmark)

    Rogatto, S R; Casartelli, C; Rainho, C A;

    1993-01-01

    chromosomes in three cases. Structural rearrangements of chromosome 2 were a finding for all cases and involved loss of material at 2q32-34. Other structural chromosome abnormalities detected involved chromosomes 4, 6, 10, 11, 12, and X. We also reviewed data on 22 cases previously reported....

  20. Transcription analysis of the dnaA gene and oriC region of the chromosome of Mycobacterium smegmatis and Mycobacterium bovis BCG, and its regulation by the DnaA protein.

    Science.gov (United States)

    Salazar, Leiria; Guerrero, Elba; Casart, Yveth; Turcios, Lilia; Bartoli, Fulvia

    2003-03-01

    The regions flanking the Mycobacterium dnaA gene have extensive sequence conservation, and comprise various DnaA boxes. Comparative analysis of the dnaA promoter and oriC region from several mycobacterial species revealed that the localization, spacing and orientation of the DnaA boxes are conserved. Detailed transcriptional analysis in M. smegmatis and M. bovis BCG shows that the dnaN gene of both species and the dnaA gene of M. bovis BCG are transcribed from two promoters, whereas the dnaA gene of M. smegmatis is transcribed from a single promoter. RT-PCR with total RNA showed that dnaA and dnaN were expressed in both species at all growth stages. Analysis of the promoter activity using dnaA-gfp fusion plasmids and DnaA expression plasmids indicates that the dnaA gene is autoregulated, although the degree of transcriptional autorepression was moderate. Transcription was also detected in the vicinity of oriC of M. bovis BCG, but not of M. smegmatis. These results suggest that a more complex transcriptional mechanism may be involved in the slow-growing mycobacteria, which regulates the expression of dnaA and initiation of chromosomal DNA replication.

  1. A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

    Directory of Open Access Journals (Sweden)

    Cigudosa Juan C

    2011-05-01

    Full Text Available Abstract Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs, will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents. With the extension of this analysis to an Array-CGH dataset (glioblastomas from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.

  2. Characterization of an Autism-Associated Segmental Maternal Heterodisomy of the Chromosome 15q11-13 Region

    Science.gov (United States)

    Kwasnicka-Crawford, Dorota A.; Roberts, Wendy; Scherer, Stephen W.

    2007-01-01

    Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome (PWS/AS) critical region have been described in individuals with autism. Maternal duplications and linkage disequilibrium in families with autism suggest the existence of a susceptibility locus at 15q11-q13. Here, we describe a 6-year-old girl diagnosed with autism, developmental…

  3. Brain regions involved in processing facial identity and expression are differentially selective for surface and edge information.

    Science.gov (United States)

    Harris, Richard J; Young, Andrew W; Andrews, Timothy J

    2014-08-15

    Although different brain regions are widely considered to be involved in the recognition of facial identity and expression, it remains unclear how these regions process different properties of the visual image. Here, we ask how surface-based reflectance information and edge-based shape cues contribute to the perception and neural representation of facial identity and expression. Contrast-reversal was used to generate images in which normal contrast relationships across the surface of the image were disrupted, but edge information was preserved. In a behavioural experiment, contrast-reversal significantly attenuated judgements of facial identity, but only had a marginal effect on judgements of expression. An fMR-adaptation paradigm was then used to ask how brain regions involved in the processing of identity and expression responded to blocks comprising all normal, all contrast-reversed, or a mixture of normal and contrast-reversed faces. Adaptation in the posterior superior temporal sulcus--a region directly linked with processing facial expression--was relatively unaffected by mixing normal with contrast-reversed faces. In contrast, the response of the fusiform face area--a region linked with processing facial identity--was significantly affected by contrast-reversal. These results offer a new perspective on the reasons underlying the neural segregation of facial identity and expression in which brain regions involved in processing invariant aspects of faces, such as identity, are very sensitive to surface-based cues, whereas regions involved in processing changes in faces, such as expression, are relatively dependent on edge-based cues.

  4. Involvement of sensory regions in affective experience: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Ajay eSatpute

    2015-12-01

    Full Text Available A growing body of work suggests that sensory processes may also contribute to affective experience. In this study, we performed a meta-analysis of affective experiences driven through visual, auditory, olfactory, gustatory, and somatosensory stimulus modalities including study contrasts that compared affective stimuli to matched neutral control stimuli. We found, first, that limbic and paralimbic regions, including the amygdala, anterior insula, pre-supplementary motor area and portions of orbitofrontal cortex were consistently engaged across two or more modalities. Second, early sensory input regions in occipital, temporal, piriform, mid-insular, and primary sensory cortex were frequently engaged during affective experiences driven by visual, auditory, olfactory, gustatory and somatosensory inputs. A classification analysis demonstrated that the pattern of neural activity across a contrast map diagnosed the stimulus modality driving the affective experience. These findings suggest that affective experiences are constructed from activity that is distributed across limbic and paralimbic brain regions and also activity in sensory cortical regions.

  5. Involvement of Sensory Regions in Affective Experience: A Meta-Analysis.

    Science.gov (United States)

    Satpute, Ajay B; Kang, Jian; Bickart, Kevin C; Yardley, Helena; Wager, Tor D; Barrett, Lisa F

    2015-01-01

    A growing body of work suggests that sensory processes may also contribute to affective experience. In this study, we performed a meta-analysis of affective experiences driven through visual, auditory, olfactory, gustatory, and somatosensory stimulus modalities including study contrasts that compared affective stimuli to matched neutral control stimuli. We found, first, that limbic and paralimbic regions, including the amygdala, anterior insula, pre-supplementary motor area, and portions of orbitofrontal cortex were consistently engaged across two or more modalities. Second, early sensory input regions in occipital, temporal, piriform, mid-insular, and primary sensory cortex were frequently engaged during affective experiences driven by visual, auditory, olfactory, gustatory, and somatosensory inputs. A classification analysis demonstrated that the pattern of neural activity across a contrast map diagnosed the stimulus modality driving the affective experience. These findings suggest that affective experiences are constructed from activity that is distributed across limbic and paralimbic brain regions and also activity in sensory cortical regions.

  6. Region-Specific Involvement of Actin Rearrangement-Related Synaptic Structure Alterations in Conditioned Taste Aversion Memory

    Science.gov (United States)

    Bi, Ai-Ling; Wang, Yue; Li, Bo-Qin; Wang, Qian-Qian; Ma, Ling; Yu, Hui; Zhao, Ling; Chen, Zhe-Yu

    2010-01-01

    Actin rearrangement plays an essential role in learning and memory; however, the spatial and temporal regulation of actin dynamics in different phases of associative memory has not been fully understood. Here, using the conditioned taste aversion (CTA) paradigm, we investigated the region-specific involvement of actin rearrangement-related…

  7. Verification of the Chromosome Region 9q21 Association with Pelvic Organ Prolapse Using RegulomeDB Annotations

    Directory of Open Access Journals (Sweden)

    Maryam B. Khadzhieva

    2015-01-01

    Full Text Available Pelvic organ prolapse (POP is a common highly disabling disorder with a large hereditary component. It is characterized by a loss of pelvic floor support that leads to the herniation of the uterus in or outside the vagina. Genome-wide linkage studies have shown an evidence of POP association with the region 9q21 and six other loci in European pedigrees. The aim of our study was to test the above associations in a case-control study in Russian population. Twelve SNPs including SNPs cited in the above studies and those selected using the RegulomeDB annotations for the region 9q21 were genotyped in 210 patients with POP (stages III-IV and 292 controls with no even minimal POP. Genotyping was performed using the polymerase chain reaction with confronting two-pair primers (PCR–CTPP. Association analyses were conducted for individual SNPs, 9q21 haplotypes, and SNP-SNP interactions. SNP rs12237222 with the highest RegulomeDB score 1a appeared to be the key SNP in haplotypes associated with POP. Other RegulomeDB Category 1 SNPs, rs12551710 and rs2236479 (scores 1d and 1f, resp., exhibited epistatic effects. In this study, we verified the region 9q21 association with POP in Russians, using RegulomeDB annotations.

  8. Identification and characterization of a new type of asymmetrical dicentric chromosome derived from a single maternal chromosome 18.

    Science.gov (United States)

    Lin, C C; Li, Y-C; Liu, P-P; Hsieh, L-J; Cheng, Y-M; Teng, R-H; Shi, S-L; Tsai, F-J

    2007-01-01

    Molecular cytogenetic analysis identified a new type of dicentric chromosome involving different breakpoints at 18q in a female fetus. The chromosome anomaly was designated as an asymmetrical pseudoisodicentric chromosome 18, 46,XX,psu dic(18)(pter-->q11.2::q21.3-->pter)mat. A series of BAC clones for 18q11.2 and q21.3 regions were used to identify one breakpoint within the region q11.2 between 19.8 and 21.6 Mb from the telomere of 18p and another breakpoint within q21.3 between 55.4 and 56.9 Mb from the telomere of 18p by FISH analysis. Real-time quantitative PCR and microsatellite analysis further verified that the dicentric chromosome was maternal in origin and resulted from a break-reunion between sister chromatids of a single maternal chromosome. We propose that a loop-type configuration of sister chromatids took place and that the break-reunion occurred at cross sites of the loop to form an asymmetrical isodicentric chromosome during either mitosis or meiosis. In this case, the asymmetrical pseudoisodicentric resulted in an 18pter--> q11.2 duplication and an 18q21.3-->qter deletion, which could have led to certain dysmorphic features of 18q- syndrome in this fetus.

  9. Post-zygotic breakage of a dicentric chromosome results in mosaicism for a telocentric 9p marker chromosome in a boy with developmental delay.

    Science.gov (United States)

    Pedurupillay, C R J; Misceo, D; Gamage, T H; Dissanayake, V H W; Frengen, E

    2014-01-01

    Chromosomal rearrangements resulting in an inverted duplication and a terminal deletion (inv dup del) can occur due to three known mechanisms, two of them resulting in a normal copy region between the duplicated regions. These mechanisms involve the formation of a dicentric chromosome, which undergo breakage during cell division resulting in cells with either an inverted duplication and deletion or a terminal deletion. We describe a mosaic 3 year old patient with two cell lines carrying a chromosome 9p deletion where one of the cell lines contains an additional telocentric marker chromosome. Our patient is mosaic for the product of a double breakage of a dicentric chromosome including a centric fission. Mosaicism involving different rearrangements of the same chromosome is rare and suggests an early mitotic breakage event. Chr9p terminal deletions associated with duplications have previously been reported in 11 patients. We compare the clinical features of all 12 patients including the patient that we report here. To the best to our knowledge this is a first case reported where the double breakage occurred in the dicentric derivative chromosome 9.

  10. Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA.

    Science.gov (United States)

    Mandelli, Maria Luisa; Vitali, Paolo; Santos, Miguel; Henry, Maya; Gola, Kelly; Rosenberg, Lynne; Dronkers, Nina; Miller, Bruce; Seeley, William W; Gorno-Tempini, Maria Luisa

    2016-01-01

    The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and the behavioral variant frontotemporal dementia (bvFTD) are focal neurodegenerative disorders belonging to the FTD-spectrum clinical syndromes. NfvPPA is characterized by effortful speech and/or agrammatism and left frontal atrophy, while bvFTD is characterized by social-emotional dysfunction often accompanied by right-lateralized frontal damage. Despite their contrasting clinical presentations, both disorders show prominent left anterior insula atrophy. We investigated differential patterns of insular sub-region atrophy in nfvPPA and bvFTD. Based on knowledge of insular connectivity and physiology, we hypothesized that the left superior precentral region of the dorsal anterior insula (SPGI) would be more atrophic in nvfPPA due to its critical role in motor speech, whereas the ventral anterior region would be more atrophied in bvFTD reflecting its known role in social-emotional-autonomic functions. Early stage nfvPPA and bvFTD patients matched for disease severity, age, gender and education and healthy controls participated in the study. Detailed clinical history, neurological examination, neuropsychological screening evaluation, and high-resolution T1-weighted brain magnetic resonance imaging (MRI) were collected. Voxel-based morphometry (VBM) was applied to perform group comparisons across the whole brain and in bilateral insula region of interest (ROI). Correlation analyses between insular sub-region atrophy and relevant clinical features were performed. Whole brain group comparisons between nfvPPA and bvFTD showed the expected predominantly left or right anterior insular atrophy pattern. ROI analysis of bilateral insula showed that the left SPGI was significantly more atrophied in nfvPPA compared to bvFTD, while the bilateral ventral anterior and right dorsal anterior insula sub-regions were more atrophied in bvFTD than nfvPPA. Only left SPGI volume correlated with speech production

  11. Investigating the prehistory of Tungusic peoples of Siberia and the Amur-Ussuri region with complete mtDNA genome sequences and Y-chromosomal markers.

    Directory of Open Access Journals (Sweden)

    Ana T Duggan

    Full Text Available Evenks and Evens, Tungusic-speaking reindeer herders and hunter-gatherers, are spread over a wide area of northern Asia, whereas their linguistic relatives the Udegey, sedentary fishermen and hunter-gatherers, are settled to the south of the lower Amur River. The prehistory and relationships of these Tungusic peoples are as yet poorly investigated, especially with respect to their interactions with neighbouring populations. In this study, we analyse over 500 complete mtDNA genome sequences from nine different Evenk and even subgroups as well as their geographic neighbours from Siberia and their linguistic relatives the Udegey from the Amur-Ussuri region in order to investigate the prehistory of the Tungusic populations. These data are supplemented with analyses of Y-chromosomal haplogroups and STR haplotypes in the Evenks, Evens, and neighbouring Siberian populations. We demonstrate that whereas the North Tungusic Evenks and Evens show evidence of shared ancestry both in the maternal and in the paternal line, this signal has been attenuated by genetic drift and differential gene flow with neighbouring populations, with isolation by distance further shaping the maternal genepool of the Evens. The Udegey, in contrast, appear quite divergent from their linguistic relatives in the maternal line, with a mtDNA haplogroup composition characteristic of populations of the Amur-Ussuri region. Nevertheless, they show affinities with the Evenks, indicating that they might be the result of admixture between local Amur-Ussuri populations and Tungusic populations from the north.

  12. A novel partial deletion of the Y chromosome azoospermia factor c region is caused by non-homologous recombination between palindromes and may be associated with increased sperm counts

    NARCIS (Netherlands)

    M.J. Noordam; S.K.M. van Daalen; S.E. Hovingh; C.M. Korver; F. van der Veen; S. Repping

    2011-01-01

    BACKGROUND: The male-specific region of the human Y chromosome (MSY) contains multiple testis-specific genes. Most deletions in the MSY lead to inadequate or absent sperm production. Nearly all deletions occur via homologous recombination between amplicons. Previously, we identified two P5/distal-P1

  13. Novel Insights into Chromosome Evolution in Birds, Archosaurs, and Reptiles

    Science.gov (United States)

    Farré, Marta; Narayan, Jitendra; Slavov, Gancho T.; Damas, Joana; Auvil, Loretta; Li, Cai; Jarvis, Erich D.; Burt, David W.; Griffin, Darren K.; Larkin, Denis M.

    2016-01-01

    Homologous synteny blocks (HSBs) and evolutionary breakpoint regions (EBRs) in mammalian chromosomes are enriched for distinct DNA features, contributing to distinct phenotypes. To reveal HSB and EBR roles in avian evolution, we performed a sequence-based comparison of 21 avian and 5 outgroup species using recently sequenced genomes across the avian family tree and a newly-developed algorithm. We identified EBRs and HSBs in ancestral bird, archosaurian (bird, crocodile, and dinosaur), and reptile chromosomes. Genes involved in the regulation of gene expression and biosynthetic processes were preferably located in HSBs, including for example, avian-specific HSBs enriched for genes involved in limb development. Within birds, some lineage-specific EBRs rearranged genes were related to distinct phenotypes, such as forebrain development in parrots. Our findings provide novel evolutionary insights into genome evolution in birds, particularly on how chromosome rearrangements likely contributed to the formation of novel phenotypes. PMID:27401172

  14. Involvement of the endosomal-lysosomal system correlates with regional pathology in Creutzfeldt-Jakob disease

    DEFF Research Database (Denmark)

    Kovács, Gábor G; Gelpi, Ellen; Ströbel, Thomas;

    2007-01-01

    these with the severity of neuropathologic changes. In regions with mild pathology and scant abnormal prion protein (PrP) deposition, neurons showed an increased volume of Rab5-immunopositive early endosomes. In contrast, neurons in regions with prominent pathology had an increased volume of cathepsin D- or B......-immunoreactive lysosomes. The intraneuronal distribution of cathepsin D and B diverges between Purkinje cells and frontal cortical neurons in sporadic Creutzfeldt-Jakob disease brains. We demonstrated focal intra- and perineuronal colocalization of cathepsin D and PrP. Our results indicate that effects in the ELS...

  15. Correlation of physical and genetic maps of human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1990-01-01

    This project is now progressing strongly. Thirteen somatic cell hybrids containing rearranged {number sign}16 chromosomes have been constructed, bringing the total number of hybrids constructed by the group to 27 which divides chromosome 16 into 29 regions. 170 probes have been mapped into these regions. Although this is the second progress report for this contract it essentially contains all the work carried out since the first progress report covered a period of less than three months during which little had been done other than setting up. The project has been progressing very well and has led to numerous collaborations with other groups involved in mapping this chromosome or studying genes on it. 7 refs., 1 fig., 2 tabs.

  16. Saethre-Chotzen syndrome with familial translocation at chromosome 7p22.

    Science.gov (United States)

    Reid, C S; McMorrow, L E; McDonald-McGinn, D M; Grace, K J; Ramos, F J; Zackai, E H; Cohen, M M; Jabs, E W

    1993-10-01

    Chromosome analysis of a male infant and his mother with Saethre-Chotzen syndrome demonstrated an apparently balanced translocation, t(2;7)(p23;p22). This association lends support to localization of the gene for Saethre-Chotzen syndrome to the 7p2 region and supports further involvement of gene(s) in the 7p22 region.

  17. Heterotopic neuroglial tissue: two cases involving the tongue and the buccal region

    DEFF Research Database (Denmark)

    Aanaes, Kasper; Hasselby, Jane Preuss; Bilde, Anders

    2008-01-01

    We report two rare cases of extranasal heterotopic neuroglial tissue and review the literature on the topic. The clinical, histological, and immunohistochemical features are presented. Both patients had lesions extranasally, even though the sinonasal region is the predominant site for these heter...

  18. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Science.gov (United States)

    Mengoli, Valentina; Bucciarelli, Elisabetta; Lattao, Ramona; Piergentili, Roberto; Gatti, Maurizio; Bonaccorsi, Silvia

    2014-10-01

    Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on slight differences

  19. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Directory of Open Access Journals (Sweden)

    Valentina Mengoli

    2014-10-01

    Full Text Available Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on

  20. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes.

  1. Refined genetic mapping of autosomal dominant retinitis pigmentosa locus RP18 reduces the critical region to 2 cM between D1S442 and D1S2858 on chromosome 1q.

    Science.gov (United States)

    Xu, S Y; Rosenberg, T; Gal, A

    1998-04-01

    Linkage analysis was performed on a large Danish family to refine the position of RP18, the locus for autosomal dominant retinitis pigmentosa, mapped previously between D1S534 and D1S305 in chromosome 1p13-q21. We genotyped the family members for five microsatellite-type DNA polymorphisms and mapped RP18 between D1S422 and D1S2858 to a region of less than 2 cM. No obvious candidate gene has yet been assigned to the chromosomal interval defined here.

  2. Chromosomal aberration frequencies determined by conventional methods: Parallel increases over time in the region of a petrochemical industry and throughout the Czech Republic.

    Science.gov (United States)

    Sram, Radim J; Rössner, Pavel; Beskid, Olena; Bavorova, Hana; Ocadlikova, Dana; Solansky, Ivo; Albertini, Richard J

    2007-03-20

    The rationale for cytogenetic monitoring to determine if safe maximum allowable concentrations (MAC) of genotoxic chemicals are being maintained in a workplace is that exposure levels that do not increase chromosomal aberration frequencies are without harmful effects. Such monitoring, widely used in occupational health programs in the Czech Republic (CR), includes workers exposed to 1,3-butadiene (BD) or other chemicals. Studies of BD exposed workers in the years 1992, 1993, 1994, 1998, and 2004 compared mean frequencies of cells carrying chromosomal aberrations (frequency of aberrant cells=%AB.C.) in exposed workers with those in non-exposed matched controls in the same plant or in other individuals living in the region of the same petrochemical industry. Workers potentially exposed to acrylonitrile at this site were also evaluated in 2000, along with another unexposed matched control group. The %AB.C. values of exposed workers and their controls were also compared with reference values determined for normal individuals (ages 20-59 years) throughout the CR. Substantial discrepancies were noted between subjects in the region of the petrochemical industry (exposed workers and controls) for the years 2000 and 2004 and the reference CR-wide normal values that had been determined during an earlier time period. The matched non-exposed controls at the petrochemical industry site showed a mean %AB.C. value of 1.56+/-1.23% (N=25) in 1998; this rose to a mean of 2.65+/-2.29% (N=33) in 2000. In 2004, values for non-exposed matched controls at the industry site were 2.64+/-1.75% for males (N=25) and 2.38+/-1.74% (N=26) for females. However, the earlier determined CR-wide %AB.C. mean reference values for normal individuals were 1.77+/-1.16% (N=1305) for the interval 1977-1988 and 1.45+/-1.17% (N=2140) for the interval 1991-1999. As both reference values are substantially lower than those determined in 2000 and 2004 for the non-exposed matched controls at the petrochemical

  3. A 6. 5-Mb yeast artificial chromosome contig incorporating 33 DNA markers on the human X chromosome at Xq22

    Energy Technology Data Exchange (ETDEWEB)

    Vetrie, D.; Kendall, E.; Coffey, A.; Hassock, S.; Collins, J.; Todd, C.; Bobrow, M.; Bentley, D.R. (Paediatric Research Unit, London (United Kingdom)); Lehrach, H. (Imperial Cancer Research Fund, London (United Kingdom)); Harris, A. (John Radcliffe Hospital, Oxford (United Kingdom))

    1994-01-01

    The Xq22 region of the human X chromosome contains genes for a number of inherited disorders. Sixty-nine yeast artificial chromosome clones have been isolated and assembled into a 6.5-Mb contig that contains 33 DNA markers localized to this region. This contig extends distally from DXS366 to beyond DXS87 and includes the genes involved in X-linked agammaglobulinemia (btk), Fabry disease (GLA), and Pelizaeus-Merzbacher disease (PLP). The order of markers in this contig is consistent with the known genetic and physical mapping information of Xq22. This cloned material provides a source from which to isolate other genes located in this part of the X chromosome. 45 refs., 2 figs., 2 tabs.

  4. Mitotic recombination of chromosome 17 in astrocytomas

    Energy Technology Data Exchange (ETDEWEB)

    James, C.D.; Carlbom, E.; Nordenskjold, M.; Collins, V.P.; Cavenee, W.K. (Ludwig Institute for Cancer Research, Montreal (Canada))

    1989-04-01

    Allelic combinations at seven loci on human chromosome 17 defined by restriction fragment length polymorphisms were determined in tumor and normal tissues from 35 patients with gliomas. Loss of constitutional heterozygosity at one or more of these loci was observed in 8 of the 24 tumors displaying astrocytic differentiation and in the single primitive neuroectodermal tumor examined. The astrocytomas showing these losses included examples of each adult malignancy grade of the disease, including glioblastoma (malignancy grade IV), and seven of them demonstrated concurrent maintenance of heterozygosity for at least one chromosome 17 locus. Determination of allele dosage together with the genotypic data indicated that the tumor chromosomes 17 were derived by mitotic recombination in 7 of the 9 cases with shared homozygosity of the region 17p11.2-ptr in all cases. In contrast, tumors of oligodendrocytic, ependymal, or mixed cellular differentiation did not exhibit loss of alleles at any of the loci examined. These data suggest that the somatic attainment of homozygosity for loci on chromosome 17p is frequently associated with the oncogenesis of central nervous system tumors, particularly those showing solely astrocytic differentiation, and that mitotic recombination mapping is a useful approach towards the subregional localization of a locus whose rearrangement is involved in this disease.

  5. Mapping of the regions involved in self-interaction of rice stripe virus P3 protein.

    Science.gov (United States)

    Zhao, S L; Hao, J H; Xue, Y N; Liang, C Y

    2016-03-01

    Rice stripe virus (RSV) protein P3 is a suppressor of RNA silencing in plants. P3 has been shown by biomolecular fluorescence complementation assay to self-interact in planta but the regions responsible for homotypic interaction have not been determined. Here we analyzed the domains for the self-interaction of P3 by using yeast two-hybrid, co-immunoprecipitation and fluorescence experiments. The results showed that P3 was also able to interact with itself in yeast and insect cells. The domain responsible for P3-P3 interaction was mapped to amino acids 15-30 at the N-terminal region of P3. Furthermore, subcellular localization suggested that the homo-oligomerization was the prerequisite for P3 to form larger protein aggregates in the nucleus of insect cell.

  6. Four chromosomal breakpoints and four new probes mark out a 10-cM region encompassing the fragile-X locus (FRAXA).

    Science.gov (United States)

    Rousseau, F; Vincent, A; Rivella, S; Heitz, D; Triboli, C; Maestrini, E; Warren, S T; Suthers, G K; Goodfellow, P; Mandel, J L

    1991-01-01

    We report the validation and use of a cell hybrid panel which allowed us a rapid physical localization of new DNA probes in the vicinity of the fragile-X locus (FRAXA). Seven regions are defined by this panel, two of which lie between DXS369 and DXS296, until now the closest genetic markers that flank FRAXA. Of those two interesting regions, one is just distal to DXS369 and defined by probe 2-71 (DXS476), which is not polymorphic. The next one contains probes St677 (DXS463) and 2-34 (DXS477), which are within 130 kb and both detect TaqI RFLPs. The combined informativeness of these two probes is 30%. We cloned from an irradiation-reduced hybrid line another new polymorphic probe, Do33 (DXS465; 42% heterozygosity). This probe maps to the DXS296 region, proximal to a chromosomal breakpoint that corresponds to the Hunter syndrome locus (IDS). The physical order is thus Cen-DXS369-DXS476-(DXS463,DXS477)-(DXS296, DXS465)-IDS-DXS304-tel. We performed a linkage analysis for five of these markers in both the Centre d'Etude du Polymorphisme Humain families and in a large set of fragile-X families. This establishes that DXS296 is distal to FRAXA. The relative position of DXS463 and DXS477 with respect to FRAXA remains uncertain, but our results place them genetically halfway between DXS369 and DXS304. Thus the DXS463-DXS477 cluster defines presently either the closest proximal or the closest distal polymorphic marker with respect to FRAXA. The three new polymorphic probes described here have a combined heterozygosity of 60% and represent a major improvement for genetic analysis of fragile-X families, in particular for diagnostic applications.

  7. Adipose and muscle tissue gene expression of two genes (NCAPG and LCORL located in a chromosomal region associated with cattle feed intake and gain.

    Directory of Open Access Journals (Sweden)

    Amanda K Lindholm-Perry

    Full Text Available A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG and ligand dependent nuclear receptor corepressor-like protein (LCORL are positional candidate genes within this region. Previously identified genetic markers in both genes were associated with average daily gain (ADG and average daily feed intake (ADFI in a crossbred population of beef steers. These markers were also associated with hot carcass weight, ribeye area and adjusted fat thickness suggesting that they may have a role in lean muscle growth and/or fat deposition. The purpose of this study was to determine whether the transcript abundance of either of these genes in cattle adipose and muscle tissue was associated with variation in feed intake and average daily gain phenotypes. Transcript abundance for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose only, cows and steers using real-time polymerase chain reaction. In the adipose tissue from cows and heifers, a negative correlation between LCORL transcript abundance and ADFI were detected (P = 0.05. In the muscle tissue from cows, transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009. A positive correlation between LCORL transcript abundance from muscle tissue of steers and ADFI was detected (P = 0.04. LCORL protein levels in the muscle of steers were investigated and were associated with ADFI (P = 0.01. These data support our earlier genetic associations with ADFI and ADG within this region and represent the potential for biological activity of these genes in the muscle and adipose tissues of beef cattle; however, they also suggest that sex, age and/or nutrition-specific interactions may affect the expression of NCAPG and LCORL in these tissues.

  8. Y-chromosomal genes affecting male fertility: A review

    Science.gov (United States)

    Dhanoa, Jasdeep Kaur; Mukhopadhyay, Chandra Sekhar; Arora, Jaspreet Singh

    2016-01-01

    The mammalian sex-chromosomes (X and Y) have evolved from autosomes and are involved in sex determination and reproductive traits. The Y-chromosome is the smallest chromosome that consists of 2-3% of the haploid genome and may contain between 70 and 200 genes. The Y-chromosome plays major role in male fertility and is suitable to study the evolutionary relics, speciation, and male infertility and/or subfertility due to its unique features such as long non-recombining region, abundance of repetitive sequences, and holandric inheritance pattern. During evolution, many holandric genes were deleted. The current review discusses the mammalian holandric genes and their functions. The commonly encountered infertility and/or subfertility problems due to point or gross mutation (deletion) of the Y-chromosomal genes have also been discussed. For example, loss or microdeletion of sex-determining region, Y-linked gene results in XY males that exhibit female characteristics, deletion of RNA binding motif, Y-encoded in azoospermic factor b region results in the arrest of spermatogenesis at meiosis. The holandric genes have been covered for associating the mutations with male factor infertility. PMID:27536043

  9. Y-chromosomal genes affecting male fertility: A review

    Directory of Open Access Journals (Sweden)

    Jasdeep Kaur Dhanoa

    2016-07-01

    Full Text Available The mammalian sex-chromosomes (X and Y have evolved from autosomes and are involved in sex determination and reproductive traits. The Y-chromosome is the smallest chromosome that consists of 2-3% of the haploid genome and may contain between 70 and 200 genes. The Y-chromosome plays major role in male fertility and is suitable to study the evolutionary relics, speciation, and male infertility and/or subfertility due to its unique features such as long non-recombining region, abundance of repetitive sequences, and holandric inheritance pattern. During evolution, many holandric genes were deleted. The current review discusses the mammalian holandric genes and their functions. The commonly encountered infertility and/or subfertility problems due to point or gross mutation (deletion of the Y-chromosomal genes have also been discussed. For example, loss or microdeletion of sex-determining region, Y-linked gene results in XY males that exhibit female characteristics, deletion of RNA binding motif, Y-encoded in azoospermic factor b region results in the arrest of spermatogenesis at meiosis. The holandric genes have been covered for associating the mutations with male factor infertility.

  10. The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region

    Institute of Scientific and Technical Information of China (English)

    Qiuling Xu; Tao Liu; Shuping Chen; Yonghui Gao; Junying Wang; Lina Qiao; Junling Liu

    2012-01-01

    In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanli (ST36) and Yanglingquan (GB34) once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold (paw withdrawal latency) was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptic cleft width and thinning of the postsynaptic density, and it significantly suppressed the down-regulation of intracellular calcium/ calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region.

  11. Assignment of the human gene for the water channel of renal collecting duct Aquaporin 2 (AQP2) to chromosome 12 region q12-->q13

    NARCIS (Netherlands)

    Deen, P M; Weghuis, D O; Sinke, R J; Geurts van Kessel, A; Wieringa, B; van Os, C H

    1994-01-01

    The chromosomal localization of the gene encoding Aquaporin 2 (previously called WCH-CD), which acts as a water channel in the collecting tubules of the kidney, was determined. Southern blot hybridizations of chromosomal DNA from a panel of 25 different human-rodent hybrid cell lines assigned AQP2 t

  12. Identifying a network of brain regions involved in aversion-related processing: a cross-species translational investigation

    Directory of Open Access Journals (Sweden)

    Dave J Hayes

    2011-10-01

    Full Text Available The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e. meta-analysis and other animals (i.e. systematic review of functional neuroanatomy was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g. thalalmus, midbrain and cortical (e.g. orbitofrontal regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behaviour can often be observed.

  13. The impact of imprinting: Prader-Willi syndrome resulting from chromosome translocation, recombination, and nondisjunction

    Energy Technology Data Exchange (ETDEWEB)

    Toth-Fejel, S.; Olson, S.; Gunter, K. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1996-05-01

    Prader-Willi syndrome (PWS) is most often the result of a deletion of bands q11.2-q13 of the paternally derived chromosome 15, but it also occurs either because of maternal uniparental disomy (UPD) of this region or, rarely, from a methylation imprinting defect. A significant number of cases are due to structural rearrangements of the pericentromeric region of chromosome 15. We report two cases of PWS with UPD in which there was a meiosis I nondisjunction error involving an altered chromosome 15 produced by both a translocation event between the heteromorphic satellite regions of chromosomes 14 and 15 and recombination. In both cases, high-resolution banding of the long arm was normal, and FISH of probes D15S11, SNRPN, D15S10, and GABRB3 indicated no loss of this material. Chromosome heteromorphism analysis showed that each patient had maternal heterodisomy of the chromosome 15 short arm, whereas PCR of microsatellites demonstrated allele-specific maternal isodisomy and heterodisomy of the long arm. SNRPN gene methylation analysis revealed only a maternal imprint in both patients. We suggest that the chromosome structural rearrangements, combined with recombination in these patients, disrupted normal segregation of an imprinted region, resulting in uniparental disomy and PWS. 30 refs., 6 figs., 1 tab.

  14. Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2.

    Science.gov (United States)

    Rose, C S; King, A A; Summers, D; Palmer, R; Yang, S; Wilkie, A O; Reardon, W; Malcolm, S; Winter, R M

    1994-08-01

    Saethre-Chotzen syndrome is a common autosomal dominant form of craniosynostosis, which results in the premature fusion of cranial sutures. Craniosynostosis is commonly associated with abnormalities of 7p; Vortkamp et al. (Nature 352, 539-540) demonstrated that the GLI3 gene in 7p13 was disrupted in, patients with Greig syndrome and, more recently, the linkage of genetic markers from 7p with the Saethre-Chotzen syndrome locus has been reported (2,3). Here we report the analysis by fluorescence in situ hybridization of four patients with Saethre-Chotzen syndrome associated with apparently balanced translocations involving band 7p21.2 and different reciprocal chromosomes. We show that in all four patients the breakpoints in 7p are situated within a 6 cM region flanked by the genetic markers D7S488 and D7S493. These results provide further evidence that the genetic locus for Saethre-Chotzen syndrome is located in distal 7p.

  15. A novel invertebrate trophic factor related to invertebrate neurotrophins is involved in planarian body regional survival and asexual reproduction.

    Science.gov (United States)

    Bueno, David; Fernàndez-Rodríguez, Juana; Cardona, Albert; Hernàndez-Hernàndez, Victor; Romero, Rafael

    2002-12-15

    Trophic factors are a heterogeneous group of molecules that promote cell growth and survival. In freshwater planarians, the small secreted protein TCEN49 is linked to the regional maintenance of the planarian central body region. To investigate its function in vivo, we performed loss-of-function and gain-of-function experiments by RNA interference and by the implantation of microbeads soaked in TCEN49, respectively. We show that TCEN49 behaves as a trophic factor involved in central body region neuron survival. In planarian tail regenerates, tcen49 expression inhibition by double-stranded RNA interference causes extensive apoptosis in various cell types, including nerve cells. This phenotype is rescued by the implantation of microbeads soaked in TCEN49 after RNA interference. On the other hand, in organisms committed to asexual reproduction, both tcen49 mRNA and its protein are detected not only in the central body region but also in the posterior region, expanding from cells close to the ventral nerve chords. In some cases, the implantation of microbeads soaked in TCEN49 in the posterior body region drives organisms to reproduce asexually, and the inhibition of tcen49 expression obstructs this process, suggesting a link between the central nervous system, TCEN49, regional induction, and asexual reproduction. Finally, the distribution of TCEN49 cysteine and tyrosine residues also points to a common evolutionary origin for TCEN49 and molluscan neurotrophins.

  16. Structural rearrangements of chromosome 15 satellites resulting in Prader-Willi syndrome suggest a complex mechanism for uniparental disomy

    Energy Technology Data Exchange (ETDEWEB)

    Toth-Fijel, S.; Gunter, K.; Olson, S. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1994-09-01

    We report two cases of PWS in which there was abnormal meiosis I segregation of chromosome 15 following a rare translocation event between the heteromorphic satellite regions of chromosomes 14 and 15 and an apparent meiotic recombination in the unstable region of 15q11.2. PWS and normal appearing chromosomes in case one prompted a chromosome 15 origin analysis. PCR analysis indicated maternal isodisomy for the long arm of chromosome. However, only one chromosome 15 had short arm heteromorphisms consistent with either paternal or maternal inheritance. VNTR DNA analysis and heteromorphism data suggest that a maternal de novo translocation between chromosome 14 and 15 occurred prior to meiosis I. This was followed by recombination between D15Z1 and D15S11 and subsequent meiosis I nondisjunction. Proband and maternal karyotype display a distamycin A-DAPI positive region on the chromosome 14 homolog involved in the translocation. Fluorescent in situ hybridization (FISH) analyses of ONCOR probes D15S11, SNRPN, D15S11 and GABRB 3 were normal, consistent with the molecular data. Case two received a Robertsonian translocation t(14;15)(p13;p13) of maternal origin. Chromosome analysis revealed a meiosis I error producing UPD. FISH analysis of the proband and parents showed normal hybridization of ONCOR probes D15Z1, D15S11, SNRPN, D15S10 and GABRB3. In both cases the PWS probands received a structurally altered chromosome 15 that had rearranged with chromosome 14 prior to meiosis. If proper meiotic segregation is dependent on the resolution of chiasmata and/or the binding to chromosome-specific spindle fibers, then it may be possible that rearrangements of pericentric or unstable regions of the genome disrupt normal disjunction and lead to uniparental disomy.

  17. A genome-wide association study identifies a region at chromosome 12 as a potential susceptibility locus for restenosis after percutaneous coronary intervention

    Science.gov (United States)

    Sampietro, M. Lourdes; Trompet, Stella; Verschuren, Jeffrey J.W.; Talens, Rudolf P.; Deelen, Joris; Heijmans, Bastiaan T.; de Winter, Robbert J.; Tio, Rene A.; Doevendans, Pieter A.F.M.; Ganesh, Santhi K.; Nabel, Elizabeth G.; Westra, Harm-Jan; Franke, Lude; van den Akker, Erik B.; Westendorp, Rudi G.J.; Zwinderman, Aeilko H.; Kastrati, Adnan; Koch, Werner; Slagboom, P.Eline; de Knijff, Peter; Jukema, J. Wouter

    2011-01-01

    Percutaneous coronary intervention (PCI) has become an effective therapy to treat obstructive coronary artery diseases (CAD). However, one of the major drawbacks of PCI is the occurrence of restenosis in 5–25% of all initially treated patients. Restenosis is defined as the re-narrowing of the lumen of the blood vessel, resulting in renewed symptoms and the need for repeated intervention. To identify genetic variants that are associated with restenosis, a genome-wide association study (GWAS) was conducted in 295 patients who developed restenosis (cases) and 571 who did not (controls) from the GENetic Determinants of Restenosis (GENDER) study. Analysis of ∼550 000 single nucleotide polymorphisms (SNPs) in GENDER was followed by a replication phase in three independent case–control populations (533 cases and 3067 controls). A potential susceptibility locus for restenosis at chromosome 12, including rs10861032 (Pcombined = 1.11 × 10−7) and rs9804922 (Pcombined = 1.45 × 10−6), was identified in the GWAS and replication phase. In addition, both SNPs were also associated with coronary events (rs10861032, Padditive = 0.005; rs9804922, Padditive = 0.023) in a trial based cohort set of elderly patients with (enhanced risk of) CAD (PROSPER) and all-cause mortality in PROSPER (rs10861032, Padditive = 0.007; rs9804922, Padditive = 0.013) and GENDER (rs10861032, Padditive = 0.005; rs9804922, Padditive = 0.023). Further analysis suggests that this locus could be involved in regulatory functions. PMID:21878436

  18. Differential impact of REM sleep deprivation on cytoskeletal proteins of brain regions involved in sleep regulation.

    Science.gov (United States)

    Rodríguez-Vázquez, Jennifer; Camacho-Arroyo, Ignacio; Velázquez-Moctezuma, Javier

    2012-01-01

    Rapid eye movement (REM) sleep is involved in memory consolidation, which implies synaptic plasticity. This process requires protein synthesis and the reorganization of the neural cytoskeleton. REM sleep deprivation (REMSD) has an impact on some neuronal proteins involved in synaptic plasticity, such as glutamate receptors and postsynaptic density protein 95, but its effects on cytoskeletal proteins is unknown. In this study, the effects of REMSD on the content of the cytoskeletal proteins MAP2 and TAU were analyzed. Adult female rats were submitted to selective REMSD by using the multiple platform technique. After 24, 48 or 72 h of REMSD, rats were decapitated and the following brain areas were dissected: pons, preoptic area, hippocampus and frontal cortex. Protein extraction and Western blot were performed. Results showed an increase in TAU content in the pons, preoptic area and hippocampus after 24 h of REMSD, while in the frontal cortex a significant increase in TAU content was observed after 72 h of REMSD. A TAU content decrease was observed in the hippocampus after 48 h of REMSD. Interestingly, a marked increase in TAU content was observed after 72 h of REMSD. MAP2 content only increased in the preoptic area at 24 h, and in the frontal cortex after 24 and 72 h of REMSD, without significant changes in the pons and hippocampus. These results support the idea that REM sleep plays an important role in the organization of neural cytoskeleton, and that this effect is tissue-specific.

  19. Acquisition of Paleolithic toolmaking abilities involves structural remodeling to inferior frontoparietal regions.

    Science.gov (United States)

    Hecht, E E; Gutman, D A; Khreisheh, N; Taylor, S V; Kilner, J; Faisal, A A; Bradley, B A; Chaminade, T; Stout, D

    2015-07-01

    Human ancestors first modified stones into tools 2.6 million years ago, initiating a cascading increase in technological complexity that continues today. A parallel trend of brain expansion during the Paleolithic has motivated over 100 years of theorizing linking stone toolmaking and human brain evolution, but empirical support remains limited. Our study provides the first direct experimental evidence identifying likely neuroanatomical targets of natural selection acting on toolmaking ability. Subjects received MRI and DTI scans before, during, and after a 2-year Paleolithic toolmaking training program. White matter fractional anisotropy (FA) showed changes in branches of the superior longitudinal fasciculus leading into left supramarginal gyrus, bilateral ventral precentral gyri, and right inferior frontal gyrus pars triangularis. FA increased from Scan 1-2, a period of intense training, and decreased from Scan 2-3, a period of reduced training. Voxel-based morphometry found a similar trend toward gray matter expansion in the left supramarginal gyrus from Scan 1-2 and a reversal of this effect from Scan 2-3. FA changes correlated with training hours and with motor performance, and probabilistic tractography confirmed that white matter changes projected to gray matter changes and to regions that activate during Paleolithic toolmaking. These results show that acquisition of Paleolithic toolmaking skills elicits structural remodeling of recently evolved brain regions supporting human tool use, providing a mechanistic link between stone toolmaking and human brain evolution. These regions participate not only in toolmaking, but also in other complex functions including action planning and language, in keeping with the hypothesized co-evolution of these functions.

  20. Reproductive outcome in 3 families with a satellited chromosome 4 with review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Arn, P.H.; Younie, L.; Russo, S. [Nemours Children`s Clinic, Jacksonville, FL (United States)] [and others

    1995-07-03

    We describe 3 families segregating for a translocation of the nucleolus organizer region (NOR) onto chromosome 4. Review of previously reported cases of translocations involving NOR and chromosome 4 shows that these translocations may be associated with variable reproductive outcomes. We provide evidence that imprinting is not the mechanism responsible for the variable reproductive outcomes in the case of satellited 4p chromosomes; this may offer indirect support for a ribosomal gene position effect. Translocated ribosomal genes may influence the expression of neighboring genes and could explain the variable phenotypes in individuals with satellited nonacrocentric chromosomes. We recommend that prenatal counseling of individuals with satellited nonacrocentric chromosomes should be cautious. 23 refs., 2 figs., 1 tab.

  1. Hypertensive brainstem encephalopathy involving deep supratentorial regions: does only blood pressure matter?

    Directory of Open Access Journals (Sweden)

    Jong-Ho Park

    2010-04-01

    Full Text Available We report on a 42-year-old female patient who presented with high arterial blood pressure of 245/150 mmHg and hypertensive brainstem encephalopathy that involved the brainstem and extensive supratentorial deep gray and white matter. The lesions were nearly completely resolved several days after stabilization of the arterial blood pressure. Normal diffusion-weighted imaging findings and high apparent diffusion coefficient values suggested that the main pathomechanism was vasogenic edema owing to severe hypertension. On the basis of a literature review, the absolute value of blood pressure or whether the patient can control his/her blood pressure seems not to be associated with the degree of the lesions evident on magnetic resonance imaging. It remains to be determined if the acceleration rate and the duration of elevated arterial blood pressure might play a key role in the development of the hypertensive encephalopathy pattern.

  2. Reducing uncertainty in flood frequency analyses: A comparison of local and regional approaches involving information on extreme historical floods

    Science.gov (United States)

    Halbert, K.; Nguyen, C. C.; Payrastre, O.; Gaume, E.

    2016-10-01

    This paper proposes a detailed comparison of local and regional approaches for flood frequency analyses, with a special emphasis on the effects of (a) the information on extreme floods used in the analysis (historical data or recent extreme floods observed at ungauged sites), and (b) the assumptions associated with regional approaches (statistical homogeneity of considered series, independence of observations). The results presented are based on two case studies: the Ard e ̀ che and Argens rivers regions in south-east of France. Four approaches are compared: 1 - local analysis based on continuous measured series, 2 - local analysis with historical information, 3 - regional index-flood analysis based on continuous series, 4 - regional analysis involving information on extremes (including both historical floods and recent floods observed at ungauged sites). The inference approach used is based on a GEV distribution and a Bayesian Monte Carlo Markov Chain approach for parameters estimation. The comparison relies both on (1) available observed datasets and (2) Monte Carlo simulations in order to evaluate the effects of sampling variability and to analyze the possible influence of regional heterogeneities. The results indicate that a relatively limited level of regional heterogeneity, which may not be detected through homogeneity tests, may significantly affect the performances of regional approaches. These results also illustrate the added value of information on extreme floods, historical floods or recent floods observed at ungauged sites, in both local and regional approaches. As far as possible, gathering such information and incorporating it into flood frequency studies should be promoted. Finally, the presented Monte Carlo simulations appear as an interesting analysis tool for adapting the estimation strategy to the available data for each specific case study.

  3. Investigating the cortical regions involved in MEP modulation in tDCS

    Directory of Open Access Journals (Sweden)

    Ricardo eSalvador

    2015-10-01

    Full Text Available Transcranial magnetic stimulation (TMS is used in several studies to evaluate cortical excitability changes induced by transcranial direct current stimulation (tDCS of the primary motor cortex. Interpretation of these results, however, is hindered by the very different spatial distribution of the electric field (E-field induced by the two techniques and by the different target neurons that they might act upon. In this study we used the finite element method to calculate the E-field distribution induced by TMS and tDCS in a realistically shaped model of a human head. A model of a commercially available figure-8 coil was placed over a position above the identified hand knob (HK region. We also modelled two configurations of bipolar tDCS montages with one of the electrodes placed over the HK and a return electrode over the contralateral orbital region. The electrodes over the HK were either rectangular in shape, with an area of 35cm2 or cylindrical with an area of π cm2 (1 cm radius. To compare the E-field distribution in TMS and the two tDCS models, average values of the E-field’s magnitude as well as the polar and azimuthal angle were investigated in the HK region and premotor areas. The results show that both techniques induce fields with different magnitudes and directions in the HK: the field in tDCS is predominantly perpendicular to the cortical surface, contrary to what happens in TMS where the field is mostly parallel to it. In the premotor areas, the magnitude of the E-field induced in TMS was well below the accepted threshold for MEP generation, 100 V/m. In tDCS, the magnitude of the field in these areas was comparable to that induced at the HK with a significant component perpendicular to the cortical surface. These results indicate that tDCS and TMS target preferentially different neuronal structures at the HK. Besides, they show that premotor areas may play a role in the tDCS-induced after effects on motor cortex excitability.

  4. Chromosomal divergence and evolutionary inferences in Rhodniini based on the chromosomal location of ribosomal genes

    Directory of Open Access Journals (Sweden)

    Sebastian Pita

    2013-05-01

    Full Text Available In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae. The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome or both sex chromosomes (X and Y chromosomes. This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.

  5. Sex chromosome rearrangements in Polyphaga beetles.

    Science.gov (United States)

    Dutrillaux, A M; Dutrillaux, B

    2009-01-01

    The presence of a parachute sex chromosome bivalent (Xyp) at metaphase I of male meiosis is a well-known characteristic of Coleoptera, present in almost all families of this order and assumed to represent their ancestral sex chromosome formula. Sex chromosomes appear to be manifold more frequently involved in inter-chromosomal rearrangements than the average of the nine autosomal pairs usually forming their karyotype. This leads to various formulae such as neo-sex, multiple sex and perhaps unique sex chromosomes. These rearrangements alter the intimate association between sex chromosomes and nucleolar proteins, which are usual components of the Xyp. Different situations, selected in a series of 125 mitotic and meiotic cytogenetic studies of Polyphaga beetle species, are reported and discussed, with the aim to improve our knowledge on the mechanisms of sex chromosome rearrangements, the relationships with nucleoli and the consequences on dosage compensation and chromosome segregation.

  6. Deletion of Chromosomal Region 8p21 Confers Resistance to Bortezomib and Is Associated with Upregulated Decoy TRAIL Receptor Expression in Patients with Multiple Myeloma.

    Directory of Open Access Journals (Sweden)

    Adil Doganay Duru

    Full Text Available Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM that undergo autologous stem cell transplantation (ASCT. In this study, we aimed to identify the immunological and molecular consequences of del(8(p21 with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8(p21 responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8(p21 including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8(p21 to TRAIL/APO2L mediated apoptosis, in cells with del(8(p21 bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8(p21 to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8(p21.

  7. Label Free Chromosome Translocation Detection with Silicon nanowires

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Andersen, Karsten Brandt; Frøhling, Kasper Bayer;

    is a Fluorescent In Situ Hybridization, which is laborious and involves use of expensive reagents [1]. Here we present a label free technique for detection of chromosome translocations. As a proof of concept detection of chromosome translocation between chromosome 3 (Chr3) and chromosome 9 (Chr9) was chosen....

  8. Chromosomal rearrangement interferes with meiotic X chromosome inactivation.

    Science.gov (United States)

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-10-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC). Here, we report on the transcriptional down-regulation of genes within the unsynapsed region of the rearranged mouse chromosome 17, and on the subsequent disturbance of X chromosome inactivation. The partial transcriptional suppression of genes in the unsynapsed chromatin was most prominent prior to the mid-pachytene stage of primary spermatocytes. Later, during the mid-late pachytene, the rearranged autosomes colocalized with the XY body, and the X chromosome failed to undergo proper transcriptional silencing. Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation.

  9. Monoamines tissue content analysis reveals restricted and site-specific correlations in brain regions involved in cognition.

    Science.gov (United States)

    Fitoussi, A; Dellu-Hagedorn, F; De Deurwaerdère, P

    2013-01-01

    The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems are deeply involved in cognitive processes via their influence on cortical and subcortical regions. The widespread distribution of these monoaminergic networks is one of the main difficulties in analyzing their functions and interactions. To address this complexity, we assessed whether inter-individual differences in monoamine tissue contents of various brain areas could provide information about their functional relationships. We used a sensitive biochemical approach to map endogenous monoamine tissue content in 20 rat brain areas involved in cognition, including 10 cortical areas and examined correlations within and between the monoaminergic systems. Whereas DA content and its respective metabolite largely varied across brain regions, the NA and 5-HT contents were relatively homogenous. As expected, the tissue content varied among individuals. Our analyses revealed a few specific relationships (10%) between the tissue content of each monoamine in paired brain regions and even between monoamines in paired brain regions. The tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence when looking at a specific brain region. Most correlations found between cortical areas were positive while some cortico-subcortical relationships regarding the DA, NA and 5-HT tissue contents were negative, in particular for DA content. In conclusion, this work provides a useful database of the monoamine tissue content in numerous brain regions. It suggests that the regulation of these neuromodulatory systems is achieved mainly at the terminals, and that each of these systems contributes to the regulation of the other two.

  10. Influence of the presence of B chromosomes on DNA damage in Crepis capillaris.

    Directory of Open Access Journals (Sweden)

    Jolanta Kwasniewska

    Full Text Available The sensitivity of different plant species to mutagenic agents is related to the DNA content and organization of the chromatin, which have been described in ABCW and bodyguard hypotheses, respectively. Plant species that have B chromosomes are good models for the study of these hypotheses. This study presents an analysis of the correlation between the occurrence of B chromosomes and the DNA damage that is induced by the chemical mutagen, maleic hydrazide (MH, in Crepis capillaris plants using comet assay. The presence of B chromosomes has a detectable impact on the level of DNA damage. The level of DNA damage after MH treatment was correlated with the number of B chromosomes and it was observed that it increased significantly in plants with 3B chromosomes. We did not find evidence of the protective role from chemical mutagens of the constitutive heterochromatin for euchromatin in relation to DNA damage. The DNA damage involving the 25S rDNA sequences was analyzed using the comet-FISH technique. Fragmentation within or near the 25S rDNA involved the loci on the A and B chromosomes. The presence of B chromosomes in C. capillaris cells had an influence on the level of DNA damage that involves the 25S rDNA region.

  11. The interaction between the membrane-proximal external region and the N-trimer region of HIV- 1 gp41: Involvement in viral fusion

    Institute of Scientific and Technical Information of China (English)

    LI Jing; LU Lu; WU Fan; CHEN Xi; NIU Ben; JIANG ShiBo; CHEN YingHua

    2009-01-01

    The membrane proximal external region (MPER) of gp41 is extremely conserved among diverse HIV-1 variants, implying its important role in viral infection. Interestingly, two of the most broadly neutralizing antibodies, 2F5 and 4E10, specifically recognize this region. Our previous study demonstrated that the antigenicity and immunogenicity of 4E10 epitope are affected by remodeling gp41 fusion core, sug-gesting that the MPER may be associated with gp41 core and involved in gp41-mediated membrane fusion. Here we measured the binding activity of 4E10 epitope peptide (D4E10P) with various gp41 core-derived peptides and found that the N-trimer region in a construct designated N-trimer-6HB in-teracted significantly with D4E10P. Using N-trimer-6HB to screen a phage library, we identified a motif (WF) located in 4E10 epitope that may play a certain role in the interaction of gp41 MPER with the N-trimer in gp41 fusion core and, we thus speculated upon the potential involvement of MPER in the usion process between viral envelope and target cell membrane.

  12. Improving global and regional resolution of male lineage differentiation by simple single-copy Y-chromosomal short tandem repeat polymorphisms

    Science.gov (United States)

    Vermeulen, Mark; Wollstein, Andreas; van der Gaag, Kristiaan; Lao, Oscar; Xue, Yali; Wang, Qiuju; Roewer, Lutz; Knoblauch, Hans; Tyler-Smith, Chris; de Knijff, Peter; Kayser, Manfred

    2012-01-01

    We analysed 67 short tandem repeat polymorphisms from the non-recombining part of the Y-chromosome (Y-STRs), including 49 rarely-studied simple single-copy (ss)Y-STRs and 18 widely-used Y-STRs, in 590 males from 51 populations belonging to 8 worldwide regions (HGDP-CEPH panel). Although autosomal DNA profiling provided no evidence for close relationship, we found 18 Y-STR haplotypes (defined by 67 Y-STRs) that were shared by two to five men in 13 worldwide populations, revealing high and widespread levels of cryptic male relatedness. Maximal (95.9%) haplotype resolution was achieved with the best 25 out of 67 Y-STRs in the global dataset, and with the best 3-16 markers in regional datasets (89.6-100% resolution). From the 49 rarely-studied ssY-STRs, the 25 most informative markers were sufficient to reach the highest possible male lineage differentiation in the global (92.2% resolution), and 3-15 markers in the regional datasets (85.4-100%). Considerably lower haplotype resolutions were obtained with the three commonly-used Y-STR sets (Minimal Haplotype, PowerPlex Y®, and AmpFlSTR® Yfiler®). Six ssY-STRs (DYS481, DYS533, DYS549, DYS570, DYS576 and DYS643) were most informative to supplement the existing Y-STR kits for increasing haplotype resolution, or – together with additional ssY-STRs - as a new set for maximizing male lineage differentiation. Mutation rates of the 49 ssY-STRs were estimated from 403 meiotic transfers in deep-rooted pedigrees, and ranged from ~4.8×10−4 for 31 ssY-STRs with no mutations observed to 1.3×10−2 and 1.5×10−2 for DYS570 and DYS576, respectively, the latter representing the highest mutation rates reported for human Y-STRs so far. Our findings thus demonstrate that ssY-STRs are useful for maximizing global and regional resolution of male lineages, either as a new set, or when added to commonly-used Y-STR sets, and support their application to forensic, genealogical and anthropological studies. PMID:19647704

  13. Chromosomal imbalances revealed in primary rhabdomyosarcomas by comparative genomic hybridization

    Institute of Scientific and Technical Information of China (English)

    LI Qiao-xin; LIU Chun-xia; CHUN Cai-pu; QI Yan; CHANG Bin; LI Xin-xia; CHEN Yun-zhao; NONG Wei-xia; LI Hong-an; LI Feng

    2009-01-01

    Background Previous cytogenetic studies revealed aberrations varied among the throe subtypes of rhabdomyosarcoma. We profiled chromosomal imbalances in the different subtypes and investigated the relationships between clinical parameters and genomic aberrations.Methods Comparative genomic hybridization was used to investigate genomic imbalances in 25 cases of primary rhabdomyosarcomas and two rhabdomyosarcoma cell lines. Specimens were reviewed to determine histological type, pathological grading and clinical staging.Results Changes involving one or more regions of the genome were seen in all rhabdomyosarcomal patients. For rhabdomyosarcoma, DNA sequence gains were most frequently (>30%) seen in chromosomes 2p, 12q, 6p, 9q, 10q, 1p,2q, 6q, 8q, 15q and 18q; losses from 3p, 11p and 6p. In aggressive alveolar rhabdomyosarcoma, frequent gains were seen on chromosomes 12q, 2p, 6p, 2q, 4q, 10q and 15q; losses from 3p, 6p, 1q and 5q. For embryonic rhabdomyosarcoma, frequent gains were on 7p, 9q, 2p, 18q, 1p and 8q; losses only from 11p. Frequently gained chromosome arms of translocation associated with rhabdomyosarcoma were 12q, 2, 6, 10q, 4q and 15q; losses from 3p,6p and 5q. The frequently gained chromosome arms of nontranslocation associated with rhabdomyosarcoma were 2p,9q and 18q, while 11p and 14q were the frequently lost chromosome arms. Gains on chromosome 12q were significantly correlated with translocation type. Gains on chromosome 9q were significantly correlated with clinical staging. Conclusions Gains on chromosomes 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q and 18q and losses on chromosomes 3p, 11p and 6p may be related to rhabdomyosarcomal carcinogenesis. Furthermore, gains on chromosome 12q may be correlated with translocation and gains on chromosome 9q with the early stages of rhabdomyosarcoma.

  14. Chromosome painting of Z and W sex chromosomes in Characidium (Characiformes, Crenuchidae).

    Science.gov (United States)

    Pazian, Marlon F; Shimabukuro-Dias, Cristiane Kioko; Pansonato-Alves, José Carlos; Oliveira, Claudio; Foresti, Fausto

    2013-03-01

    Some species of the genus Characidium have heteromorphic ZZ/ZW sex chromosomes with a totally heterochromatic W chromosome. Methods for chromosome microdissection associated with chromosome painting have become important tools for cytogenetic studies in Neotropical fish. In Characidium cf. fasciatum, the Z chromosome contains a pericentromeric heterochromatin block, whereas the W chromosome is completely heterochromatic. Therefore, a probe was produced from the W chromosome through microdissection and degenerate oligonucleotide-primed polymerase chain reaction amplification. FISH was performed using the W probe on the chromosomes of specimens of this species. This revealed expressive marks in the pericentromeric region of the Z chromosome as well as a completely painted W chromosome. When applying the same probe on chromosome preparations of C. cf. gomesi and Characidium sp., a pattern similar to C. cf. fasciatum was found, while C. cf. zebra, C. cf. lagosantense and Crenuchus spilurus species showed no hybridization signals. Structural changes in the chromosomes of an ancestral sexual system in the group that includes the species C. cf. gomesi, C. cf. fasciatum and Characidium sp., could have contributed to the process of speciation and could represent a causal mechanism of chromosomal diversification in this group. The heterochromatinization process possibly began in homomorphic and homologous chromosomes of an ancestral form, and this process could have given rise to the current patterns found in the species with sex chromosome heteromorphism.

  15. First description of multivalent ring structures in eutherian mammalian meiosis: new chromosomal characterization of Cormura brevirostris (Emballonuridae, Chiroptera).

    Science.gov (United States)

    de Araújo, Ramon Everton Ferreira; Nagamachi, Cleusa Yoshiko; da Costa, Marlyson Jeremias Rodrigues; Noronha, Renata Coelho Rodrigues; Rodrigues, Luís Reginaldo Ribeiro; Pieczarka, Julio César

    2016-08-01

    Twelve specimens of the bat Cormura brevirostris (Emballonuridae: Chiroptera) were collected from four localities in the Brazilian Amazon region and analyzed by classical and molecular cytogenetics. The diploid number and autosomal fundamental number were as previously reported (2n = 22 and FNa = 40, respectively). Fluorescence in situ hybridization using rDNA probes and silver nitrate technique demonstrated the presence of two NOR sites and the presence of internal telomeric sequences at pericentromeric regions of all chromosomes with exception of Y. Based on meiotic studies and chromosome banding we suggest that the sex chromosome pair of C. brevirostris was equivocally identified as it appears in the literature. Meiotic analysis demonstrated that at diplotene-diakinesis the cells had a ring conformation involving four chromosome pairs. This suggests the occurrence of multiple reciprocal translocations among these chromosomes, which is a very rare phenomenon in vertebrates, and has never been described in Eutheria.

  16. A stable acentric marker chromosome: Possible existence of an intercalary ancient centromere at distal 8p

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Hirofumi; Fukushima, Yoshimitsu; Wakui, Keiko; Ogawa, Kioyshi [Saitama Children`s Medical Center, Iwatsuki (Japan); Okano, Tetsuroh [Kitazato Univ., Tokyo (Japan); Niikawa, Norio [Nagasaki Univ. School of Medicine (Japan)

    1994-12-01

    A centromere is considered to be an essential chromosomal component where microtubule-kinetochore interaction occurs to segregate sister chromatids faithfully and acentric chromosomes are unstable and lost through cell divisions. We report a novel marker chromosome that was acentric but stable through cell divisions. The patient was a 2-year-old girl with mental retardation, patent ductus arteriosus, and mild dysmorphic features. G-banded chromosome analysis revealed that an additional small marker chromosome was observed in all 100 cells examined. By the reverse-chromosome-painting method, the marker was found to originate from the distal region of 8p, and a subsequent two-color FISH analysis with cosmid probes around the region revealed that the marker was an inverted duplication interpreted as 8pter {yields} p23.1::p23.1 {yields} 8pter. No centromeric region was involved in the marker. By FISH, no {alpha}-satellite sequence was detected on the marker, while a telomere sequence was detected at each end. Anti-kinetochore immunostaining, using a serum from a patient with CREST (calcinosis, Raynaud syndrome, esophageal dismotility, sclerodactyly, and telangiectasia) syndrome, showed a pair of signals on the marker, which indicated that a functional kinetochore was present on the marker. The analysis of this patient might suggest the possibility that an ancient centromere sequence exists at distal 8p (8p23.1-pter) and was activated through the chromosome rearrangement in the patient.

  17. CHROMOSOME 3 MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

    Institute of Scientific and Technical Information of China (English)

    胡杰; 江澄川; 吴浩强; 彭颂先; 唐婉君; 陈商群

    2002-01-01

    Objective: To investigate whether deletion of chromosome 3 is involved in the carcinogenesis of primary glioblastoma multiforme (GBM) and to localize the possible common deletion region in the aforementioned chromosome. Methods: PCR based microsatellite polymorphism analyses were performed to detect loss of heterozygosity (LOH). Twenty-three loci on chromosome 3 were examined in 20 cases of GBM. Fluorescence-labeled primers and Perkin Elmer 377 DNA Sequencer were applied. Results: 50% informative cases of GBM displayed LOH on chromosome 3. 50% of informative cases displayed LOH on 3q and 35% on 3p. 25.6% of informative loci showed LOH in our series, in which frequent LOH were observed in the chromosomal region from loci D3S1614 (42.9%) to D3S1565 (35.3%) on 3q24(27 and at loci D3S1569 (35.3%) on 3q22(23 and D3S1289 (33.3%) on 3p14.1(14.3. Conclusion: Loss of genetic material on chromosome 3 may play an important part in the tumorigenesis of GBM. The chromosomal regions from loci D3S1614 to D3S1565 on 3q24(27 and at loci D3S1569 on 3q22(23 and D3S1289 on 3p14.1(14.3 are potential sites for novel tumor suppressor genes associated with GBM.

  18. Chromosome Analysis

    Science.gov (United States)

    1998-01-01

    Perceptive Scientific Instruments, Inc., provides the foundation for the Powergene line of chromosome analysis and molecular genetic instrumentation. This product employs image processing technology from NASA's Jet Propulsion Laboratory and image enhancement techniques from Johnson Space Center. Originally developed to send pictures back to earth from space probes, digital imaging techniques have been developed and refined for use in a variety of medical applications, including diagnosis of disease.

  19. Short communication: Imputation of markers on the bovine X chromosome.

    Science.gov (United States)

    Mao, Xiaowei; Johansson, Anna Maria; Sahana, Goutam; Guldbrandtsen, Bernt; De Koning, Dirk-Jan

    2016-09-01

    Imputation is a cost-effective approach to augment marker data for genomic selection and genome-wide association studies. However, most imputation studies have focused on autosomes. Here, we assessed the imputation of markers on the X chromosome in Holstein cattle for nongenotyped animals and animals genotyped with low-density (Illumina BovineLD, Illumina Inc., San Diego, CA) chips, using animals genotyped with medium-density (Illumina BovineSNP50) chips. A total of 26,884 genotyped Holstein individuals genotyped with medium-density chips were used in this study. Imputation was carried out using FImpute V2.2. The following parameters were examined: treating the pseudoautosomal region as autosomal or as X specific, different sizes of reference groups, different male/female proportions in the reference group, and cumulated degree of relationship between the reference group and target group. The imputation accuracy of markers on the X chromosome was improved if the pseudoautosomal region was treated as autosomal. Increasing the proportion of females in the reference group improved the imputation accuracy for the X chromosome. Imputation for nongenotyped animals in general had lower accuracy compared with animals genotyped with the low-density single nucleotide polymorphism array. In addition, higher cumulative pedigree relationships between the reference group and the target animal led to higher imputation accuracy. In the future, better marker coverage of the X chromosome should be developed to facilitate genomic studies involving the X chromosome.

  20. EFFECT OF ELECTRO0-SCALP ACUPUNCTURE ON GLUCOSE METABOLISM OF THE CEREBRAL REGIONS INVOLVING MENTAL ACTIVITY IN HEAL THY PEOPLE

    Institute of Scientific and Technical Information of China (English)

    HUANG Yong(黄泳); Win Moe Htut; LI Dong-jiang(李东江); TANG An-wu(唐安戊); LI Qiu-shi(李求实)

    2004-01-01

    Objective: To observe the effect of electro-scalp acupuncture on glucose metabolism of cerebral regions involving mental activity in healthy people. Methods: A total of 6 cases of volunteer healthy subjects (3 males and 3 females) ranging in age from 22 to 36 years were subjected to this study. Changes of cerebral glucose metabolism before and after electro-scalp acupuncture were observed by using positron emission tomography (PET) and semi-quantifying analysis method. Electro-scalp acupuncture stimulation (50 Hz, 2 mA) of Middle Line of Vertex (Dingzhongxian,顶中线,MS5), Middle Line of Forehead (Ezhongxian, 额中线,MS1) and bilateral Lateral Line 1 of Forehead (Epangyixian,额旁一线,MS2) was administered for 30 minutes. Then cerebral regions of interest (ROIs) were chosen and their average glucose metabolism levels (radioactivity of 18 fluorine deoxyglucose ) were analyzed. Results:After administration of electro-scalp acupuncture, the glucose metabolism levels in bilateral frontal lobes and bilateral caudate nuclei, left cingulate gyrus and right cerebellum increased significantly in comparison with those of pre-stimulation (P<0.05). Conclusion:Electro-scalp acupuncture of MS1, MS2 and MS5 can increase the glucose metabolism of certain cerebral regions involving in mental activity in healthy subjects.

  1. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.

    OpenAIRE

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based...

  2. The mating type locus (MAT and sexual reproduction of Cryptococcus heveanensis: insights into the evolution of sex and sex-determining chromosomal regions in fungi.

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    Banu Metin

    2010-05-01

    Full Text Available Mating in basidiomycetous fungi is often controlled by two unlinked, multiallelic loci encoding homeodomain transcription factors or pheromones/pheromone receptors. In contrast to this tetrapolar organization, Cryptococcus neoformans/Cryptococcus gattii have a bipolar mating system, and a single biallelic locus governs sexual reproduction. The C. neoformans MAT locus is unusually large (>100 kb, contains >20 genes, and enhances virulence. Previous comparative genomic studies provided insights into how this unusual MAT locus might have evolved involving gene acquisitions into two unlinked loci and fusion into one contiguous locus, converting an ancestral tetrapolar system to a bipolar one. Here we tested this model by studying Cryptococcus heveanensis, a sister species to the pathogenic Cryptococcus species complex. An extant sexual cycle was discovered; co-incubating fertile isolates results in the teleomorph (Kwoniella heveanensis with dikaryotic hyphae, clamp connections, septate basidia, and basidiospores. To characterize the C. heveanensis MAT locus, a fosmid library was screened with C. neoformans/C. gattii MAT genes. Positive fosmids were sequenced and assembled to generate two large probably unlinked MAT gene clusters: one corresponding to the homeodomain locus and the other to the pheromone/receptor locus. Strikingly, two divergent homeodomain genes (SXI1, SXI2 are present, similar to the bE/bW Ustilago maydis paradigm, suggesting one or the other homeodomain gene was recently lost in C. neoformans/C. gattii. Sequencing MAT genes from other C. heveanensis isolates revealed a multiallelic homeodomain locus and at least a biallelic pheromone/receptor locus, similar to known tetrapolar species. Taken together, these studies reveal an extant C. heveanensis sexual cycle, define the structure of its MAT locus consistent with tetrapolar mating, and support the proposed evolutionary model for the bipolar Cryptococcus MAT locus revealing

  3. Sexual maldevelopment and sex reversal, chromosomal causes.

    Science.gov (United States)

    Magenis, R Ellen

    2006-01-01

    The SRY gene on the Y chromosome is the testis determining factor (TDF). It is therefore the initial male determining factor. However, phenotypic sex determination includes a cascade of genes located on autosomes as well as sex chromosomes. Aberrations of these genes may cause sexual maldevelopment or sex reversal. Abnormalities may include single gene mutations and gene loss or gain-changes may involve only sex organs or may be part of syndromes. These changes may also arise as chromosome abnormalities involving contiguous genes. Eight cases with chromosomal abnormalities involving different causative mechanisms are described herein. The most common cause is nondisjunction, including loss or gain of sex chromosomes. Less common causes are mispairing and crossing over in meiosis, chromosome breaks with repair, nonhomologous pairing due to low copy repeats and crossing over, and translocation (familial or de novo) with segregation. Cases include: [see: text].

  4. Deciphering evolutionary strata on plant sex chromosomes and fungal mating-type chromosomes through compositional segmentation.

    Science.gov (United States)

    Pandey, Ravi S; Azad, Rajeev K

    2016-03-01

    Sex chromosomes have evolved from a pair of homologous autosomes which differentiated into sex determination systems, such as XY or ZW system, as a consequence of successive recombination suppression between the gametologous chromosomes. Identifying the regions of recombination suppression, namely, the "evolutionary strata", is central to understanding the history and dynamics of sex chromosome evolution. Evolution of sex chromosomes as a consequence of serial recombination suppressions is well-studied for mammals and birds, but not for plants, although 48 dioecious plants have already been reported. Only two plants Silene latifolia and papaya have been studied until now for the presence of evolutionary strata on their X chromosomes, made possible by the sequencing of sex-linked genes on both the X and Y chromosomes, which is a requirement of all current methods that determine stratum structure based on the comparison of gametologous sex chromosomes. To circumvent this limitation and detect strata even if only the sequence of sex chromosome in the homogametic sex (i.e. X or Z chromosome) is available, we have developed an integrated segmentation and clustering method. In application to gene sequences on the papaya X chromosome and protein-coding sequences on the S. latifolia X chromosome, our method could decipher all known evolutionary strata, as reported by previous studies. Our method, after validating on known strata on the papaya and S. latifolia X chromosome, was applied to the chromosome 19 of Populus trichocarpa, an incipient sex chromosome, deciphering two, yet unknown, evolutionary strata. In addition, we applied this approach to the recently sequenced sex chromosome V of the brown alga Ectocarpus sp. that has a haploid sex determination system (UV system) recovering the sex determining and pseudoautosomal regions, and then to the mating-type chromosomes of an anther-smut fungus Microbotryum lychnidis-dioicae predicting five strata in the non

  5. The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease.

    Science.gov (United States)

    Kimura, Ryo; Kamino, Kouzin; Yamamoto, Mitsuko; Nuripa, Aidaralieva; Kida, Tomoyuki; Kazui, Hiroaki; Hashimoto, Ryota; Tanaka, Toshihisa; Kudo, Takashi; Yamagata, Hidehisa; Tabara, Yasuharu; Miki, Tetsuro; Akatsu, Hiroyasu; Kosaka, Kenji; Funakoshi, Eishi; Nishitomi, Kouhei; Sakaguchi, Gaku; Kato, Akira; Hattori, Hideyuki; Uema, Takeshi; Takeda, Masatoshi

    2007-01-01

    We scanned throughout chromosome 21 to assess genetic associations with late-onset Alzheimer disease (AD) using 374 Japanese patients and 375 population-based controls, because trisomy 21 is known to be associated with early deposition of beta-amyloid (Abeta) in the brain. Among 417 markers spanning 33 Mb, 22 markers showed associations with either the allele or the genotype frequency (P KCNJ6 genes. In logistic regression, the DYRK1A (dual-specificity tyrosine-regulated kinase 1A) gene, located in the Down syndrome critical region, showed the highest significance [OR = 2.99 (95% CI: 1.72-5.19), P = 0.001], whereas the RUNX1 gene showed a high odds ratio [OR = 23.3 (95% CI: 2.76-196.5), P = 0.038]. DYRK1A mRNA level in the hippocampus was significantly elevated in patients with AD when compared with pathological controls (P < 0.01). DYRK1A mRNA level was upregulated along with an increase in the Abeta-level in the brain of transgenic mice, overproducing Abeta at 9 months of age. In neuroblastoma cells, Abeta induced an increase in the DYRK1A transcript, which also led to tau phosphorylation at Thr212 under the overexpression of tau. Therefore, the upregulation of DYRK1A transcription results from Abeta loading, further leading to tau phosphorylation. Our result indicates that DYRK1A could be a key molecule bridging between beta-amyloid production and tau phosphorylation in AD.

  6. Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region.

    Science.gov (United States)

    Ogata, Tsutomu; Kagami, Masayo

    2016-02-01

    Human chromosome 14q32.2 carries paternally expressed genes including DLK1 and RTL1, and maternally expressed genes including MEG3 and RTL1as, along with the germline-derived DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived MEG3-DMR. Consistent with this, paternal uniparental disomy 14 (upd(14)pat), and epimutations (hypermethylations) and microdeletions affecting the IG-DMR and/or the MEG3-DMR of maternal origin, result in a unique phenotype associated with characteristic face, a small bell-shaped thorax with coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly and polyhydramnios. Recently, the name 'Kagami-Ogata syndrome' (KOS) has been approved for this clinically recognizable disorder. Here, we review the current knowledge about KOS. Important findings include the following: (1) the facial 'gestalt' and the increased coat-hanger angle constitute pathognomonic features from infancy through childhood/puberty; (2) the unmethylated IG-DMR and MEG3-DMR of maternal origin function as the imprinting control centers in the placenta and body respectively, with a hierarchical interaction regulated by the IG-DMR for the methylation pattern of the MEG3-DMR in the body; (3) RTL1 expression level becomes ~2.5 times increased in the absence of functional RTL1as-encoded microRNAs that act as a trans-acting repressor for RTL1; (4) excessive RTL1 expression and absent MEG expression constitute the primary underlying factor for the phenotypic development; and (5) upd(14)pat accounts for approximately two-thirds of KOS patients, and epimutations and microdeletions are identified with a similar frequency. Furthermore, we refer to diagnostic and therapeutic implications.

  7. The involvement of tetA and tetE tetracycline resistance genes in plasmid and chromosomal resistance of Aeromonas in Brazilian strains

    Directory of Open Access Journals (Sweden)

    Ilana Teruszkin Balassiano

    2007-11-01

    Full Text Available This study analyzed the involvement of tetA and tetE genes in the tetracycline resistance of 16 strains of genus Aeromonas, isolated from clinical and food sources. Polymerase chain reactions revealed that 37.5% of the samples were positive for tetA, and also 37.5% were tetE positive. One isolate was positive for both genes. Only the isolate A. caviae 5.2 had its resistance associated to the presence of a plasmid, pSS2. The molecular characterization of pSS2 involved the construction of its restriction map and the determination of its size. The digestion of pSS2 with HindIII originated two fragments (A and B that were cloned separately into the pUC18 vector. The tetA gene was shown to be located on the HindIII-A fragment by PCR. After transforming a tetracycline-sensitive strain with pSS2, the transformants expressed the resistance phenotype and harbored a plasmid whose size was identical to that of pSS2. The results confirmed the association between pSS2 and the tetracycline resistance phenotype, and suggest a feasible dissemination of tetA and tetE among strains of Aeromonas. This study suggests the spreading tetA and tetE genes in Aeromonas in Brazil and describes a resistance plasmid that probably contributes to the dissemination of the resistance.

  8. Microdissection and chromosome painting of X and B chromosomes in Locusta migratoria.

    Science.gov (United States)

    Teruel, María; Cabrero, Josefa; Montiel, Eugenia E; Acosta, Manuel J; Sánchez, Antonio; Camacho, Juan Pedro M

    2009-01-01

    Acquisition of knowledge of the nature and DNA content of B chromosomes has been triggered by a collection of molecular techniques, one of which, microdissection, has provided interesting results in a number of B chromosome systems. Here we provide the first data on the molecular composition of B chromosomes in Locusta migratoria, after microdissection of the B and X chromosomes, DNA amplification by one (B) or two (X) different methods, and chromosome painting. The results showed that B chromosomes share at least two types of repetitive DNA sequences with the A chromosomes, suggesting that Bs in this species most likely arose intraspecifically. One of these repetitive DNAs is located on the heterochromatic distal half of the B chromosome and in the pericentromeric regions of about half of the A chromosomes, including the X. The other type of repetitive DNA is located interspersedly over the non-centromeric euchromatic regions of all A chromosomes and in an interstitial part of the proximal euchromatic half of the B chromosome. Chromosome painting, however, did not provide results sufficiently reliable to determine, in this species, which A chromosome gave rise to the B; this might be done by detailed analysis of the microdissected DNA sequences.

  9. A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal region 11q23.3 harbors loci contributing to triglycerides.

    Directory of Open Access Journals (Sweden)

    Timothy R Braun

    Full Text Available Recent genome-wide association scans (GWAS and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD. In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638 in our Asian Indian cohort from the Sikh Diabetes Study (SDS comprising 3,781 individuals (2,902 from Punjab and 879 from the US. Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C (p = 2.03×10(-26. Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037 from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG levels in this Asian Indian cohort (rs964184: p = 1.74×10(-17; rs12286037: p = 1.58×10(-2. We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP (UK and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10(-39. Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG and, consequently, diabetes and CAD.

  10. Sex chromosome diversity in Armenian toad grasshoppers (Orthoptera, Acridoidea, Pamphagidae)

    Science.gov (United States)

    Bugrov, Alexander G.; Jetybayev, Ilyas E.; Karagyan, Gayane H.; Rubtsov, Nicolay B.

    2016-01-01

    Abstract Although previous cytogenetic analysis of Pamphagidae grasshoppers pointed to considerable karyotype uniformity among most of the species in the family, our study of species from Armenia has discovered other, previously unknown karyotypes, differing from the standard for Pamphagidae mainly in having unusual sets of sex chromosomes. Asiotmethis turritus (Fischer von Waldheim, 1833), Paranocaracris rubripes (Fischer von Waldheim, 1846), and Nocaracris cyanipes (Fischer von Waldheim, 1846) were found to have the karyotype 2n♂=16+neo-XY and 2n♀=16+neo-XX, the neo-X chromosome being the result of centromeric fusion of an ancient acrocentric X chromosome and a large acrocentric autosome. The karyotype of Paranothrotes opacus (Brunner von Wattenwyl, 1882) was found to be 2n♂=14+X1X2Y and 2n♀=14+X1X1X2X2., the result of an additional chromosome rearrangement involving translocation of the neo-Y and another large autosome. Furthermore, evolution of the sex chromosomes in these species has involved different variants of heterochromatinization and miniaturization of the neo-Y. The karyotype of Eremopeza festiva (Saussure, 1884), in turn, appeared to have the standard sex determination system described earlier for Pamphagidae grasshoppers, 2n♂=18+X0 and 2n♀=18+XX, but all the chromosomes of this species were found to have small second C-positive arms. Using fluorescent in situ hybridization (FISH) with 18S rDNA and telomeric (TTAGG)n DNA repeats to yield new data on the structural organization of chromosomes in the species studied, we found that for most of them, clusters of repeats homologous to 18S rDNA localize on two, three or four pairs of autosomes and on the X. In Eremopeza festiva, however, FISH with labelled 18S rDNA painted C-positive regions of all autosomes and the X chromosome; clusters of telomeric repeats localized primarily on the ends of the chromosome arms. Overall, we conclude that the different stages of neo-Y degradation revealed in

  11. Interstitial and terminal deletion of chromosome Y in a male individual with cryptozoospermia.

    Science.gov (United States)

    Duell, T; Mathews, S; Wunderlich, B; Mittermüller, J; Schmetzer, H

    1998-04-01

    A constitutional de-novo deletion of the long arm of the Y chromosome was detected by standard cytogenetic analysis in a 38-year old male who, except for small testes and cryptozoospermia, was phenotypically normal. The deletion was further characterized by fluorescent in-situ hybridization (FISH) and digital image analysis using contigs of overlapping yeast artificial chromosome (YAC) clones, spanning almost the entire Y chromosome. These results showed that the deletion involved a large interstitial segment on the proximal long arm of the Y chromosome (Yq11.1-->Yq11.22) as well as a more distal portion of the Y chromosome, including the entire heterochromatic region (Yq11.23-->qter). The breakpoints as determined by the YAC probes were defined within the published Vergnaud intervals so that region 6B and 6C was mostly retained. However, the AZFc region harbouring the DAZ locus on distal subinterval 6F was lost in the deletion, making the absence of this region the most probable location for the patient's infertility. The data underline the usefulness of FISH as an alternative technique to conventional banding for the refined detection of chromosome Y deletions/rearrangements.

  12. [Dicentric Y chromosome].

    Science.gov (United States)

    Abdelmoula, N Bouayed; Amouri, A

    2005-01-01

    Dicentric Y chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. Here, we report the third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. We find 78 new cases for which molecular studies (PCR or FISH) have been widely applied to investigate SRY (68% of cases), GBY, ZFY, RFS4Y, GCY and different genes at AZF region. For dic(Yq), all cases (n = 20) were mosaic for 45,X and 4 of them were also mosaic for a 46,XY cell line. When breakpoints were available (15/20 cases), they were in Yp11. 50% of cases were phenotypic female and 20% phenotypic male while 20% of cases were reported with gonadal dysgenesis. Gonadal histology was defined in 8 cases but only in one case, gonadal tissu was genetically investigated because of gonadoblastoma. For dic(Yp) (n = 55), mosaicism concerned only 45,X cell line and was found in 50 cases while the remainder five cases were homogeneous. When breakpoints were available, it was at Yq11 in 50 cases and at Yq12 in two cases. 54% of cases were phenotypic female, 26% were phenotypic male and 18% were associated with genitalia ambiguous. SRY was analyzed in 33 cases, sequenced in 9 cases and was muted in only one case. Gonads were histologically explored in 34 cases and genetically investigated in 8 cases. Gonadoblastoma was found in only two cases. Through this review, it seems that phenotype-genotype correlations are still not possible and that homogeneous studies of dic(Y) in more patients using molecular tools for structural characterization of the rearranged Y chromosome and assessment of mosaicism in many organs are necessary to clarify the basis of the phenotypic heterogeneity of dicentric Y chromosomes and then to help phenotypic prediction of such chromosome rearrangement.

  13. Rapid evolutionary dynamics in a 2.8-Mb chromosomal region containing multiple prolamin and resistance gene families in Aegilops tauschii.

    Science.gov (United States)

    Dong, Lingli; Huo, Naxin; Wang, Yi; Deal, Karin; Wang, Daowen; Hu, Tiezhu; Dvorak, Jan; Anderson, Olin D; Luo, Ming-Cheng; Gu, Yong Q

    2016-09-01

    Prolamin and resistance gene families are important in wheat food use and in defense against pathogen attacks, respectively. To better understand the evolution of these multi-gene families, the DNA sequence of a 2.8-Mb genomic region, representing an 8.8 cM genetic interval and harboring multiple prolamin and resistance-like gene families, was analyzed in the diploid grass Aegilops tauschii, the D-genome donor of bread wheat. Comparison with orthologous regions from rice, Brachypodium, and sorghum showed that the Ae. tauschii region has undergone dramatic changes; it has acquired more than 80 non-syntenic genes and only 13 ancestral genes are shared among these grass species. These non-syntenic genes, including prolamin and resistance-like genes, originated from various genomic regions and likely moved to their present locations via sequence evolution processes involving gene duplication and translocation. Local duplication of non-syntenic genes contributed significantly to the expansion of gene families. Our analysis indicates that the insertion of prolamin-related genes occurred prior to the separation of the Brachypodieae and Triticeae lineages. Unlike in Brachypodium, inserted prolamin genes have rapidly evolved and expanded to encode different classes of major seed storage proteins in Triticeae species. Phylogenetic analyses also showed that the multiple insertions of resistance-like genes and subsequent differential expansion of each R gene family. The high frequency of non-syntenic genes and rapid local gene evolution correlate with the high recombination rate in the 2.8-Mb region with nine-fold higher than the genome-wide average. Our results demonstrate complex evolutionary dynamics in this agronomically important region of Triticeae species.

  14. Chromosomal patterns in human malignant astrocytomas.

    Science.gov (United States)

    Rey, J A; Bello, M J; de Campos, J M; Kusak, M E; Ramos, C; Benitez, J

    1987-12-01

    Cytogenetic analysis by direct and/or in vitro preparations was performed on 34 malignant astrocytomas. Thirty tumors showed near-diploid chromosome numbers, whereas, tritetraploid chromosome complements were present in four tumors. The most frequent chromosomal changes implied numerical deviations by a gain of chromosomes #7, #19, and #20, and by losses of #10, #22, and Y. Structural rearrangements were present in stem- or side lines of 24 tumors. Although no common chromosomal rearrangement seems to exist among those tumors, chromosomes #1, #6, #7, and #9 were predominantly involved. Polysomy and structural rearrangements of chromosome #7 could be related to the overexpression of epidermal growth factor gene, previously observed in some malignant gliomas.

  15. Chromosome X aneuploidy in Brazilian schizophrenic patients.

    Science.gov (United States)

    de Moraes, Leopoldo Silva; Khayat, André Salim; de Lima, Patrícia Danielle Lima; Lima, Eleonidas Moura; Pinto, Giovanny Rebouças; Leal, Mariana Ferreira; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

    2010-01-01

    The identification of cytogenetic abnormalities in schizophrenic patients may provide clues to the genes involved in this disease. For this reason, a chromosomal analysis of samples from 62 schizophrenics and 70 controls was performed with trypsin-Giemsa banding and fluorescence in situ hybridization of the X chromosome. A clonal pericentric inversion on chromosome 9 was detected in one male patient, and we also discovered mosaicism associated with X chromosome aneuploidy in female patients, primarily detected in schizophrenic and normal female controls over 40 years old. When compared with age-matched female controls, the frequency of X chromosome loss was not significantly different between schizophrenics and controls, except for the 40- to 49-year-old age group. Our findings suggest that the X chromosome loss seen in schizophrenic patients is inherent to the normal cellular aging process. However, our data also suggest that X chromosome gain may be correlated with schizophrenia in this Brazilian population.

  16. CHROMOSOME 17P MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

    Institute of Scientific and Technical Information of China (English)

    胡杰; 江澄川; 吴浩强; 彭颂先; 唐婉君

    2002-01-01

    Objective: To investigate whether deletion of chromosome 17 is involved in the carcinogenesis of primary glioblastoma multiforme and to localize the possible common deletion region in the aforementioned chromosome. Methods: Polymerase chain reaction-based microsatellite analysis was used to assess loss of heterozygosity (LOH) on chromosome 17 in 20 primary glioblastoma multiforme (GBM). Fifteen fluorescent dye-labeled polymorphic markers were used. Results: Thirteen of twenty (65%) GBM displayed LOH on at least one marker of chromosome 17p. Two tumors showed either LOH or non-informativeness on all markers tested. The most frequent LOH was observed at loci including D17s799 (53.3%), Dl7s1852 (53.8%), Dl7s938 (63.20/o), Dl7s831 (55.6%). The loci D17s831 (on 17pl3) and D17s799(Dl7sl852 (17p11.2(pl2) are distal and proximal to p53 respectively. The frequencies of LOH at all loci examined on chromosome 17q were relatively low (<30%). None of informative loci exhibited microsatellite instability in this study. Conclusion: Loss of genetic material on chromosome 17p may play an important role in the pathogenesis of GBM. Besides the well-known TSG p53 on 17p, other unknown TSCs associated with GBM may be present on the chromosomal regions 17pl3 and 17p11.2(pl2, which are distal and proximal to p53 respectively.

  17. Localization of latency-associated nuclear antigen (LANA) on mitotic chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Rahayu, Retno; Ohsaki, Eriko [Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Omori, Hiroko [Central Instrumentation Laboratory Research Institute for Microbial Diseases (BIKEN), Osaka University, Osaka 565-0871 (Japan); Ueda, Keiji, E-mail: kueda@virus.med.osaka-u.ac.jp [Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2016-09-15

    In latent infection of Kaposi's sarcoma-associated herpesvirus (KSHV), viral gene expression is extremely limited and copy numbers of viral genomes remain constant. Latency-associated nuclear antigen (LANA) is known to have a role in maintaining viral genome copy numbers in growing cells. Several studies have shown that LANA is localized in particular regions on mitotic chromosomes, such as centromeres/pericentromeres. We independently examined the distinct localization of LANA on mitotic chromosomes during mitosis, using super-resolution laser confocal microscopy and correlative fluorescence microscopy–electron microscopy (FM-EM) analyses. We found that the majority of LANA were not localized at particular regions such as telomeres/peritelomeres, centromeres/pericentromeres, and cohesion sites, but at the bodies of condensed chromosomes. Thus, LANA may undergo various interactions with the host factors on the condensed chromosomes in order to tether the viral genome to mitotic chromosomes and realize faithful viral genome segregation during cell division. - Highlights: • This is the first report showing LANA dots on mitotic chromosomes by fluorescent microscopy followed by electron microscopy. • LANA dots localized randomly on condensed chromosomes other than centromere/pericentromere and telomere/peritelomre. • Cellular mitotic checkpoint should not be always involved in the segregation of KSHV genomes in the latency.

  18. Healing of Broken Linear Dicentric Chromosomes in Yeast

    OpenAIRE

    Haber, James E; Thorburn, Patricia C.

    1984-01-01

    In yeast, meiotic recombination between a linear chromosome III and a haploid-viable circular chromosome will yield a dicentric, tandemly duplicated chromosome. Spores containing apparently intact dicentric chromosomes were recovered from tetrads with three viable spores. The spore containing the dicentric inherited URA3 (part of the recombinant DNA used to join regions near the ends of the chromosome into a circle) as well as HML, HMR and MAL2 (located near the two ends of a linear but dele...

  19. Comparative analysis by chromosome painting of the sex chromosomes in arvicolid rodents.

    Science.gov (United States)

    Acosta, M J; Romero-Fernández, I; Sánchez, A; Marchal, J A

    2011-01-01

    Sex chromosome evolution in mammals has been extensively investigated through chromosome-painting analyses. In some rodent species from the subfamily Arvicolinae the sex chromosomes contain remarkable features such as giant size, a consequence of heterochromatic enlargement, or asynaptic behaviour during male meiosis. Here, we have made a comparative study of the sex chromosomes in 6 arvicolid species using different probes from the X and Y chromosomes of 3 species, in order to gain knowledge about intra- or interspecific preservation of euchromatic regions. Our results clearly reveal poor conservation of the euchromatic region of the Y chromosome within these species, while the euchromatin on the X chromosome is extremely well preserved. Furthermore, we detected no clear correlation between the synaptic/asynaptic behaviour of the sex chromosomes, and the presence or absence of sequence homology within their euchromatic regions. Notably, our study has shown a new relationship between the giant sex chromosomes of 2 species, Microtus agrestis and Microtus cabrerae, that is, both X and Y share a novel region of common sequences in the euchromatin that is not present in the other species analysed. This interspecific euchromatic conservation, limited to the giant sex chromosomes, could point towards a common evolutionary origin for the heterochromatic enlargement process that has characterized the evolution of the sex chromosomes in some arvicolid species.

  20. A 5'-proximal region of the Citrus tristeza virus genome encoding two leader proteases is involved in virus superinfection exclusion.

    Science.gov (United States)

    Atallah, Osama O; Kang, Sung-Hwan; El-Mohtar, Choaa A; Shilts, Turksen; Bergua, María; Folimonova, Svetlana Y

    2016-02-01

    Superinfection exclusion (SIE), a phenomenon in which a primary virus infection prevents a secondary infection with the same or closely related virus, has been observed with various viruses. Earlier we demonstrated that SIE by Citrus tristeza virus (CTV) requires viral p33 protein. In this work we show that p33 alone is not sufficient for virus exclusion. To define the additional viral components that are involved in this phenomenon, we engineered a hybrid virus in which a 5'-proximal region in the genome of the T36 isolate containing coding sequences for the two leader proteases L1 and L2 has been substituted with a corresponding region from the genome of a heterologous T68-1 isolate. Sequential inoculation of plants pre-infected with the CTV L1L2T68 hybrid with T36 CTV resulted in superinfection with the challenge virus, which indicated that the substitution of the L1-L2 coding region affected SIE ability of the virus.

  1. A gene-based high-resolution comparative radiation hybrid map as a framework for genome sequence assembly of a bovine chromosome 6 region associated with QTL for growth, body composition, and milk performance traits

    Directory of Open Access Journals (Sweden)

    Laurent Pascal

    2006-03-01

    Full Text Available Abstract Background A number of different quantitative trait loci (QTL for various phenotypic traits, including milk production, functional, and conformation traits in dairy cattle as well as growth and body composition traits in meat cattle, have been mapped consistently in the middle region of bovine chromosome 6 (BTA6. Dense genetic and physical maps and, ultimately, a fully annotated genome sequence as well as their mutual connections are required to efficiently identify genes and gene variants responsible for genetic variation of phenotypic traits. A comprehensive high-resolution gene-rich map linking densely spaced bovine markers and genes to the annotated human genome sequence is required as a framework to facilitate this approach for the region on BTA6 carrying the QTL. Results Therefore, we constructed a high-resolution radiation hybrid (RH map for the QTL containing chromosomal region of BTA6. This new RH map with a total of 234 loci including 115 genes and ESTs displays a substantial increase in loci density compared to existing physical BTA6 maps. Screening the available bovine genome sequence resources, a total of 73 loci could be assigned to sequence contigs, which were already identified as specific for BTA6. For 43 loci, corresponding sequence contigs, which were not yet placed on the bovine genome assembly, were identified. In addition, the improved potential of this high-resolution RH map for BTA6 with respect to comparative mapping was demonstrated. Mapping a large number of genes on BTA6 and cross-referencing them with map locations in corresponding syntenic multi-species chromosome segments (human, mouse, rat, dog, chicken achieved a refined accurate alignment of conserved segments and evolutionary breakpoints across the species included. Conclusion The gene-anchored high-resolution RH map (1 locus/300 kb for the targeted region of BTA6 presented here will provide a valuable platform to guide high-quality assembling and

  2. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  3. Mitotic chromosome condensation in vertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes

  4. Sex-determining region of Y-chromosome (Sry) : master switch of sex determination%Y染色体性别决定区(Sry):性别决定关键开关

    Institute of Scientific and Technical Information of China (English)

    裴开颜; 王介东

    2012-01-01

    性发育异常在人类遗传性疾病中很常见,因此性别决定在临床和生物学研究中非常重要.Y染色体性别决定区(sex-determining region of Y-chromosome,Sry)即哺乳动物Y染色体上的睾丸决定基因片段,与性别决定密切相关.本文对Sry基因的结构功能和表达调节及其相关的性别决定分子机制进行了综述.%Sex determination is very important in clinical and biological medicine because sex development disorders are the most common genetic diseases in humans. Sex-determining region of Y-chromosome (Sry) is the mammalian Y-chromosomal testis-determining gene. It is bound up with sex determination. In this paper, we consider issues related to Sry structure and function, its expression and regulation, and relevant molecular mechanisms of sex determination.

  5. Structural insights into the human RyR2 N-terminal region involved in cardiac arrhythmias

    Energy Technology Data Exchange (ETDEWEB)

    Borko, Ľubomír; Bauerová-Hlinková, Vladena, E-mail: vladena.bauerova@savba.sk; Hostinová, Eva; Gašperík, Juraj [Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava (Slovakia); Beck, Konrad [Cardiff University School of Dentistry, Heath Park, Cardiff CF14 4XY Wales (United Kingdom); Lai, F. Anthony [Cardiff University School of Medicine, Cardiff CF14 4XN Wales (United Kingdom); Zahradníková, Alexandra, E-mail: vladena.bauerova@savba.sk [Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava (Slovakia); Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava (Slovakia); Ševčík, Jozef, E-mail: vladena.bauerova@savba.sk [Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava (Slovakia)

    2014-11-01

    X-ray and solution structures of the human RyR2 N-terminal region were obtained under near-physiological conditions. The structure exhibits a unique network of interactions between its three domains, revealing an important stabilizing role of the central helix. Human ryanodine receptor 2 (hRyR2) mediates calcium release from the sarcoplasmic reticulum, enabling cardiomyocyte contraction. The N-terminal region of hRyR2 (amino acids 1–606) is the target of >30 arrhythmogenic mutations and contains a binding site for phosphoprotein phosphatase 1. Here, the solution and crystal structures determined under near-physiological conditions, as well as a homology model of the hRyR2 N-terminal region, are presented. The N-terminus is held together by a unique network of interactions among its three domains, A, B and C, in which the central helix (amino acids 410–437) plays a prominent stabilizing role. Importantly, the anion-binding site reported for the mouse RyR2 N-terminal region is notably absent from the human RyR2. The structure concurs with the differential stability of arrhythmogenic mutations in the central helix (R420W, I419F and I419F/R420W) which are owing to disparities in the propensity of mutated residues to form energetically favourable or unfavourable contacts. In solution, the N-terminus adopts a globular shape with a prominent tail that is likely to involve residues 545–606, which are unresolved in the crystal structure. Docking the N-terminal domains into cryo-electron microscopy maps of the closed and open RyR1 conformations reveals C{sup α} atom movements of up to 8 Å upon channel gating, and predicts the location of the leucine–isoleucine zipper segment and the interaction site for spinophilin and phosphoprotein phosphatase 1 on the RyR surface.

  6. Normal phenotype with paternal uniparental isodisomy for chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Blouin, J.L.; Avramopoulos, D. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)); Pangalos, C.; Antonarakis, S.E.

    1993-11-01

    Uniparental disomy (UPD) involving several different chromosomes has been described in several cases of human pathologies. In order to investigate whether UPD for chromosome 21 is associated with abnormal phenotypes, the authors analyzed DNA polymorphisms in DNA from a family with de novo Robertsonian translocation t(21q;21q). The proband was a healthy male with 45 dup(21q) who was ascertained through his trisomy 21 offspring. No phenotypic abnormalities were noted in the physical exam, and his past medical history was unremarkable. The authors obtained genotypes for the proband and his parents' leukocyte DNAs from 17 highly informative short sequence repeat polymorphisms that map in the pericentromeric region and along the entire length of 21q. The order of the markers has been previously determined through the linkage and physical maps of this chromosome. For the nine informative markers there was no maternal allele contribution to the genotype of the proband; in addition, there was always reduction to homozygosity of a paternal allele. These data indicated that there was paternal uniparental isodisomy for chromosome 21 (pUPiD21). The authors conclude that pUPiD21 is not associated with abnormal phenotypes and that there are probably no imprinted genes on chromosome 21. 36 refs., 3 figs.

  7. Chromosome aberrations induced by zebularine in triticale.

    Science.gov (United States)

    Ma, Xuhui; Wang, Qing; Wang, Yanzhi; Ma, Jieyun; Wu, Nan; Ni, Shuang; Luo, Tengxiao; Zhuang, Lifang; Chu, Chenggen; Cho, Seong-Woo; Tsujimoto, Hisashi; Qi, Zengjun

    2016-07-01

    Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.

  8. Homologies between human and marmoset (Callithrix jacchus) chromosomes revealed by comparative chromosome painting

    Energy Technology Data Exchange (ETDEWEB)

    Sherlock, J.K.; Griffin, D.K.; Delhanty, J.D.A.; Parrington, J.M. [Univ. College London (United Kingdom)

    1996-04-15

    Regions of DNA homology between human and marmoset (Callithrix jacchus) chromosomes have been demonstrated using fluorescence in situ hybridization. All 24 chromosome paints and two centromere repeat sequences from Homo sapiens (HSA) have been annealed to previously G-banded metaphase spreads of Callithrix jacchus. All human paint probes, except Y, successfully hybridized to marmoset chromosomes. Fifteen of them hybridized to one region only, seven to two regions, and paint 1 to three regions. Homologies proposed from previous banding comparisons have been confirmed for HSA 2, 4-6, 10-12, 18, 19, 21, and X and partially confirmed for HSA 1 and 3, but were not in agreement for HSA 14 and 17. Human centromere repeat sequences for X and 18 did not hybridize to marmoset chromosomes. Because, at present, there is the confusing situation of several different numbering systems for marmoset chromosomes, we propose a new simpler nomenclature based on descending order of chromosome size. 25 refs., 3 figs.

  9. Origin and spread of the SRY gene on the X and Y chromosomes of the rodent Microtus cabrerae: role of L1 elements.

    Science.gov (United States)

    Marchal, Juan A; Acosta, Manuel J; Bullejos, Mónica; Díaz de la Guardia, Rafael; Sánchez, Antonio

    2008-02-01

    In the rodent species Microtus cabrerae, males as well as females present several copies of the SRY gene, a single-copy gene located on the Y chromosome in most mammals. Using different PCR approaches, we have characterized the sequence, structure, and organization of the SRY copies and their flanking regions distributed on the X and Y chromosomes of this species. All copies of SRY analyzed, including those from the Y chromosome, proved to be nonfunctional pseudogenes, as they have internal stop codons. In addition, we demonstrated the association of SRY pseudogenes with different fragments of L1 and LTR retroelements in both sex chromosomes of M. cabrerae. Examining the possible origin of SRY pseudogene and retroposons association, we propose that retroposons could have been involved in the mechanism of SRY gene amplification on the Y chromosome and in the transference of the Y-linked SRY copies to the X-chromosome heterochromatin.

  10. Chromosomal and regional localization of the loci for IGKC, IGGC, ALDB, HOXB, GPT, and PRNP in the American mink (Mustela vison): comparisons with human and mouse

    DEFF Research Database (Denmark)

    Khlebodarova, TM; Malchenko, Sergey; Matveeva, NM;

    1995-01-01

    Chromosomal localization of the genes for gamma- and kappa-immunoglobulins (IGGC and IGKC, respectively), aldolase B (ALDB), prion protein (PRNP), homeo box B (HOXB), and glutamate pyruvate transaminase (GPT) were determined with the use of mink-rodent hybrid cells. Analysis of segregation...

  11. Fine mapping of the chromosome 5B region carrying closely linked rust resistance genes Yr47 and Lr52 in wheat

    Science.gov (United States)

    The widely effective and linked rust resistance genes Yr47 and Lr52 were previously mapped in the short arm of chromosome 5B in two F3 populations (Aus28183/Aus27229 and Aus28187/Aus27229). The Aus28183/Aus27229 F3 population was advanced to generate an F6 recombinant inbred line (RIL) population t...