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Sample records for chromosome 1p36 region

  1. A region of consistent deletion in neuroblastoma maps within human chromosome 1p36.2-36.3

    SciTech Connect

    White, P.S.; Maris, J.M.; Beltinger, C.

    1995-06-06

    Deletion of the short arm of human chromosome 1 is the most common cytogenetic abnormality observed in neuroblastoma. To characterize the region of consistent deletion, we performed loss of heterozygosity (LOH) studies on 122 neuroblastoma tumor samples with 30 distal chromosome 1p polymorphisms. LOH was detected in 32 of the 122 tumors (26%). A single region of LOH, marked distally by D1Z2 and proximally by D1S228, was detected in all tumors demonstrating loss. Also, cells from a patient with a constitutional deletion of 1p36, and from a neuroblastoma cell line with a small 1p36 deletion, were analyzed by fluorescence in situ hybridization. Cells from both sources had interstitial deletions of 1p36.2-36.3 which overlapped the consensus region of LOH defined by the tumors. Interstitial deletion in the constitutional case was confirmed by allelic loss studies using the panel of polymorphic markers. Four proposed candidate genes-DAN, ID3 (heir-1), CDC2L1 (p58), and TNFR2-were shown to lie outside of the consensus region of allelic loss, as defined by the above deletions. These results more precisely define the location of a neuroblastoma suppressor gene within 1p36.2-36.3, eliminating 33 centimorgans of proximal 1p36 from consideration. Furthermore, a consensus region of loss, which excludes the four leading candidate genes, was found in all tumors with 1p36 LOH. 31 refs., 4 figs.

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

    SciTech Connect

    Denton, P.; Gere, S.; Wolpert, C.

    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.

  3. Partial monosomy of chromosome 1p36.3: A distinctive phenotype

    SciTech Connect

    Reish, O.; Berry, S.A.; King. R.A.

    1994-09-01

    We describe a series of five patients with a partial monosomy of 1p36.3 presenting with a similar syndromic appearance. The phenotype of deletion 1p36.3 patients includes abnormal facies, multiple congenital malformations, and mental retardation.The ages of the patients in our series ranged from 3 to 50 years. As the deletion is very small, detection in the present cases relied upon high resolution G-band analyses and was confirmed with FISH in cases 3 and 5. Patients 2 and 3 were diagnosed as adults; thus smaller deletions in 1p36.33 may be associated with longer life expectancy, but include the critical region for the above phenotype. We noted that the dysmorphic features of the patients are more prominent with older age and are difficult to appreciate in infancy. Observation of this specific 1p36 appears as a white, terminal G-band; detection of a small partial deletion or rearrangement may require greater than 550 band level resolution. FISH utilizing a probe to 1pter can facilitate and confirm these analyses.

  4. Chromosome 1p36 in migraine with aura: association study of the 5HT(1D) locus.

    PubMed

    Thompson, Miles D; Noble-Topham, Sandra; Percy, Maire E; Andrade, Danielle M; Ebers, George C

    2012-01-01

    Migraine with aura (MA) may share some but not all risk factors with other forms of migraine. As common migraine without aura (MO) has been associated with the chromosome 1p36 locus, we tested its involvement in MA by using two-point parametric linkage analysis to analyze 64 multiplex MA families. A logarithm of the odds score of 1.9 was suggestive of chromosome 1p36 linkage to MA. The transmission disequilibrium test analysis was then performed in 79 nuclear families with one MA parent and one MA offspring. We identified the presence of genetic association at chromosome 1p36 with MA (P=0.045, Bonferroni corrected): the locus encoding the 5HT(1D) receptor gene. Although these data suggest that the 1p36 locus may protect against MA, consistent with the role of the 5HT(1D) receptor in migraine treatment with triptan drugs, the study is subject to the limitations associated with studying a small number of affected families. As a result, we contrast evidence suggesting that the chromosome 1p36 locus is strongly MO associated with our finding that 1p36 has a more limited contribution to MA in the families we analyzed. Further work using a genome-wide association study approach in familial typical migraine, consisting of those affected by MO or MA, will serve to further distinguish how and why MA differs from MO. PMID:22107845

  5. 1p36 deletion syndrome: an update

    PubMed Central

    Jordan, Valerie K; Zaveri, Hitisha P; Scott, Daryl A

    2015-01-01

    Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are the most common terminal deletions in humans. Medical problems commonly caused by terminal deletions of 1p36 include developmental delay, intellectual disability, seizures, vision problems, hearing loss, short stature, distinctive facial features, brain anomalies, orofacial clefting, congenital heart defects, cardiomyopathy, and renal anomalies. Although 1p36 deletion syndrome is considered clinically recognizable, there is significant phenotypic variation among affected individuals. This variation is due, at least in part, to the genetic heterogeneity seen in 1p36 deletions which include terminal and interstitial deletions of varying lengths located throughout the 30 Mb of DNA that comprise chromosome 1p36. Array-based copy number variant analysis can easily identify genomic regions of 1p36 that are deleted in an affected individual. However, predicting the phenotype of an individual based solely on the location and extent of their 1p36 deletion remains a challenge since most of the genes that contribute to 1p36-related phenotypes have yet to be identified. In addition, haploinsufficiency of more than one gene may contribute to some phenotypes. In this article, we review recent successes in the effort to map and identify the genes and genomic regions that contribute to specific 1p36-related phenotypes. In particular, we highlight evidence implicating MMP23B, GABRD, SKI, PRDM16, KCNAB2, RERE, UBE4B, CASZ1, PDPN, SPEN, ECE1, HSPG2, and LUZP1 in various 1p36 deletion phenotypes. PMID:26345236

  6. Multiple quantitative trait loci for cortical and trabecular bone regulation map to mid-distal mouse chromosome 4 that shares linkage homology to human chromosome 1p36.

    PubMed

    Beamer, Wesley G; Shultz, Kathryn L; Coombs, Harold F; Horton, Lindsay G; Donahue, Leah Rae; Rosen, Clifford J

    2012-01-01

    The mid-distal region of mouse chromosome 4 (Chr 4) is homologous with human Chr 1p36. Previously, we reported that mouse Chr 4 carries a quantitative trait locus (QTL) with strong regulatory effect on volumetric bone mineral density (vBMD). The intent of this study is to utilize nested congenic strains to decompose the genetic complexity of this gene-rich region. Adult females and males from 18 nested congenic strains carrying discrete C3H sequences were phenotyped for femoral mineral and volume by pQCT and for trabecular bone volume (BV), tissue volume (TV), trabecular number (Trab.no), and trabecular thickness (Trab.thk) by MicroCT 40. Our data show that the mouse Chr 4 region consists of at least 10 regulatory QTL regions that affected either or both pQCT and MicroCT 40 phenotypes. The pQCT phenotypes were typically similar between sexes, whereas the MicroCT 40 phenotypes were divergent. Individual congenic strains contained one to seven QTL regions. These regions conferred large positive or negative effects in some congenic strains, depending on the particular bone phenotype. The QTL regions II to X are syntenic with human 1p36, containing from 1 to 102 known genes. We identified 13 candidate genes that can be linked to bone within these regions. Six of these genes were linked to osteoblasts, three linked to osteoclasts, and two linked to skeletal development. Three of these genes have been identified in Genome Wide Association Studies (GWAS) linked to 1p36. In region III, there is only one gene, Lck, which conferred negative pQCT and MicroCT 40 phenotypes in both sexes. This gene is important to development and functioning of T cells, has been associated with osteoclast activity, and represents a novel bone regulatory gene that merits further experimental evaluation. In summary, congenic strains are powerful tools for identifying regulatory regions that influence bone biology and offer models for testing hypotheses about gene-gene and gene

  7. FISH analysis of a patient with a constitutional 1p36 deletion defines a region for a neuroblastoma tumor suppressor gene

    SciTech Connect

    Biegel, J.; Hilliard, C.; White, P.

    1994-09-01

    Molecular and cytogenetic studies of neuroblastoma have implicated the presence of one or more tumor suppressor genes on chromosome 1p. We previously reported a neuroblastoma patient with a constitutional interstitial deletion of 1p36. As one means of further defining the deleted region, we have analyzed a series of chromosome 1p36 specific probes by FISH to metaphase chromosomes from a lymphoblastoid cell line established from the patient. We have also tested these probes on a neuroblastoma cell line, NGP, which has a t(1;15) translocation involving 1p36. The probes analyzed to date in order from centromere to telomere include ID-3 (heir-1), D1S56, D1S160, and CDC2L1 (p58). Cosmids for ID-3 and D1S56 were present in 2 copies and proximal to the breakpoint in the constitutional case, and retained on the derivative 1 in NGP. CDC2L1 was also present in 2 copies in the constitutional case, but is distal to the deletion. In NGP, CDC2L1 was translocated to the derivative 15. The D1S160 locus was deleted from one of the chromosomes 1 in the constitutional case, and was present in three copies in NGP: on the normal chromosome 1, the derivative chromosome 1, and the derivative chromosome 15. Molecular studies have suggested that there is a duplication involving this region in NGP, and so it is not clear where the translocation breakpoint is in this cell line. These studies have localized a critical region for a neuroblastoma tumor suppressor gene to 1p36.2, distal to D1S56, proximal to CDC2L1, and including D1S160. This region overlaps with the smallest area of deletion defined by loss of heterozygosity studies of primary neuroblastomas and neuroblastoma cell lines. Additional studies with probes that flank the D1S160 locus will facilitate a molecular cloning approach for a neuroblastoma tumor suppressor gene.

  8. Assignment of the human FKBP12-rapamycin-associated protein (FRAP) gene to chromosome 1p36 by fluorescence in situ hybridization

    SciTech Connect

    Moore, P.A.; Rosen, C.A.; Carter, K.C.

    1996-04-15

    This report describes the localization of the human FKBP12-rapamycin-associated protein (FRAP) gene to human chromosome 1p36 using fluorescence in situ hybridization. This protein is the binding site for rapamycin and FK506, two potent immunosuppressive drugs. 12 refs., 1 fig.

  9. Case report of individual with cutaneous immunodeficiency and novel 1p36 duplication

    PubMed Central

    Hatter, Alyn D; Soler, David C; Curtis, Christine; Cooper, Kevin D; McCormick, Thomas S

    2016-01-01

    Introduction Crusted or Norwegian scabies is an infectious skin dermatopathology usually associated with an underlying immunodeficiency condition. It is caused when the mite Sarcoptes scabiei infects the skin, and the immune system is unable to control its spread, leading to a massive hyperinfestation with a simultaneous inflammatory and hyperkeratotic reaction. This is the first report of a novel 1p36 duplication associated with a recurrent infection of crusted scabies. Case report We describe a 34-year-old patient with a cutaneous immunodeficiency characterized by recurrent crusted scabies infestation, diffuse tinea, and recurrent staphylococcal cellulitis, who we suspected had an undiagnosed syndrome. The patient also suffered from mental retardation, renal failure, and premature senescence. A cytogenetic fluorescence in situ hybridization analysis revealed a 9.34 Mb duplication within the short (p) arm of chromosome 1, precisely from 1p36.11 to 1p36.21, with an adjacent 193 kb copy gain entirely within 1p36.11. In addition, chromosome 4 had a 906 kb gain in 4p16.1 and chromosome 9 had a 81 kb copy gain in 9p24.3. Over 100 genes localized within these duplicated regions. Gene expression array revealed 82 genes whose expression changed >1.5-fold compared to a healthy age-matched skin control, but among them only the lipolytic enzyme arylacetamide deacetylase-like 3 was found within the duplicated 1p36 region of chromosome 1. Discussion Although genetic duplications in the 1p36 region have been previously described, our report describes a novel duplicative variant within the 1p36 region. The patient did not have a past history of immunosuppression but was afflicted by a recurrent case of crusted scabies, raising the possibility that the recurrent infection was associated with the 1p36 genetic duplication. Conclusion To our knowledge, the specific duplicated sequence between 1p36.11 and p36.21 found in our patient has never been previously reported. We reviewed and

  10. Characterization of the human gene for microfibril-associated glycoprotein (MFAP2), assignment to chromosome 1p36.1-p35, and linkage to D1S170

    SciTech Connect

    Faraco, J.; Bashir, M.; Rosenbloom, J.

    1995-02-10

    Microfibril-associated glycoprotein, MAGP (gene symbol MFAP2), is a component of connective tissue microfibrils and a candidate for involvement in the etiology of inherited connective tissue diseases. We have cloned a human MAGP cDNA that is highly homologous to the previously characterized bovine and murine genes. Like the bovine and murine loci, the human gene has eight coding exons, but it contains two alternatively used 5{prime} untranslated exons, whereas only one untranslated exon was described in the bovine and murine Magp genes. By using rodent x human somatic cell hybrid panels and fluorescence chromosomal in situ hybridization, we have assigned the locus to human chromosome 1p36.1-p35. An insertion/ deletion polymorphism has been identified within intron 7. Linkage analysis between this polymorphism and markers on distal chromosome 1 revealed that MAGP is tightly linked to the anonymous marker D1S170. Physical mapping revealed a distance of <100 kb between the two markers. This information can be used to screen for linkage in families with microfibrillar abnormalities that are not linked to the fibrillin genes on chromosomes 15 or 5. 24 refs., 5 figs., 1 tab.

  11. Is 1p36 deletion associated with anterior body wall defects?

    PubMed

    Çöllü, Medis; Yüksel, Şirin; Şirin, Başak Kumbasar; Abbasoğlu, Latif; Alanay, Yasemin

    2016-07-01

    Epispadias and exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects), respectively constitute the most benign and severe ends of the bladder exstrophy-epispadias complex (BEEC) spectrum. In 2009, El-Hattab et al. reported the first patient with OEIS complex associated with a chromosome 1p36 deletion. Here we report a second patient with 1p36 deletion who also has classic bladder exstrophy, supporting the possible role of genes in this region in the development of BEEC. The absence of omphalocele and imperforate anus in our patient places him toward classic bladder exstrophy while presence of spina bifida and the absence of coccyx suggest an overlap with OEIS complex. An additional differential diagnosis is the pentalogy of Cantrell in our patient as he also has a diaphragmatic hernia and an incomplete sternum. This is the second observation of a ventral midline birth defect in association with 1p36 deletion syndrome, following El-Hattab et al.'s report [2009]. The three genes (NOCL2, DVL1, and MMP23B) discussed as possible candidates are also among the deleted ones in our patient, supporting the possible role of these genes in BEEC spectrum. © 2016 Wiley Periodicals, Inc. PMID:27144803

  12. Novel airway findings in a patient with 1p36 deletion syndrome.

    PubMed

    Ferril, Geoffrey R; Barham, Henry P; Prager, Jeremy D

    2014-01-01

    1p36 deletion syndrome comprises a phenotypic presentation that includes central nervous system, cardiac, and craniofacial anomalies. There has been no report of associated airway anomalies with this syndrome. We present here a case report and literature review. Prenatally, amniocentesis for chromosomal analysis was performed on our patient, with results consistent with 1p36 deletion syndrome. Respiratory distress and unsuccessful attempts at intubation prompted transfer to Children's Hospital of Colorado. Microlaryngoscopy was subsequently performed, revealing a persistent buccopharyngeal membrane and unidentifiable larynx. Emergent tracheostomy was then performed to secure the airway. Airway anomalies may be associated with 1p36 deletion syndrome. PMID:24290305

  13. De Novo Mutations of RERE Cause a Genetic Syndrome with Features that Overlap Those Associated with Proximal 1p36 Deletions.

    PubMed

    Fregeau, Brieana; Kim, Bum Jun; Hernández-García, Andrés; Jordan, Valerie K; Cho, Megan T; Schnur, Rhonda E; Monaghan, Kristin G; Juusola, Jane; Rosenfeld, Jill A; Bhoj, Elizabeth; Zackai, Elaine H; Sacharow, Stephanie; Barañano, Kristin; Bosch, Daniëlle G M; de Vries, Bert B A; Lindstrom, Kristin; Schroeder, Audrey; James, Philip; Kulch, Peggy; Lalani, Seema R; van Haelst, Mieke M; van Gassen, Koen L I; van Binsbergen, Ellen; Barkovich, A James; Scott, Daryl A; Sherr, Elliott H

    2016-05-01

    Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are associated with developmental delay, intellectual disability, and defects involving the brain, eye, ear, heart, and kidney. Arginine-glutamic acid dipeptide repeats (RERE) is located in the proximal 1p36 critical region. RERE is a widely-expressed nuclear receptor coregulator that positively regulates retinoic acid signaling. Animal models suggest that RERE deficiency might contribute to many of the structural and developmental birth defects and medical problems seen in individuals with 1p36 deletion syndrome, although human evidence supporting this role has been lacking. In this report, we describe ten individuals with intellectual disability, developmental delay, and/or autism spectrum disorder who carry rare and putatively damaging changes in RERE. In all cases in which both parental DNA samples were available, these changes were found to be de novo. Associated features that were recurrently seen in these individuals included hypotonia, seizures, behavioral problems, structural CNS anomalies, ophthalmologic anomalies, congenital heart defects, and genitourinary abnormalities. The spectrum of defects documented in these individuals is similar to that of a cohort of 31 individuals with isolated 1p36 deletions that include RERE and are recapitulated in RERE-deficient zebrafish and mice. Taken together, our findings suggest that mutations in RERE cause a genetic syndrome and that haploinsufficiency of RERE might be sufficient to cause many of the phenotypes associated with proximal 1p36 deletions. PMID:27087320

  14. Morbid obesity in a child with monosomy 1p36 syndrome

    PubMed Central

    Zagalo, Ana; Dias, Patricia; Pereira, Carla; Sampaio, Maria de Lurdes

    2012-01-01

    The monosomy 1p36 syndrome is a cause of syndromic obesity. It is characterised by psychomotor delay, hypotonia and typical craniofacial dysmorphism. Other features commonly associated are behavioural anomalies including hyperphagia and self-injuring, seizures, congenital heart disease and hypothyroidism. The authors report the case of a 9-year and 5-month-boy referred to the paediatric endocrinology clinics for morbid obesity. Clinical findings were generalised obesity with a body mass index >95th centile, acanthosis nigricans of the neck, arms with self inflicted lesions, deep-set eyes, straight eyebrows, broad nasal bridge and pointed chin. He was unable to walk and had no expressive language. Cytogenetic analysis identified 1p36.33-pter deletion (~139 Mb terminal deletion in chromosome 1 short arm) and Y chromosome duplication. The blood analysis showed insulin resistance and dyslipidaemia. The authors emphasise the need to consider monosomy 1p36 as a cause of severe psychomotor delay and obesity. PMID:22605691

  15. Further delineation of nonhomologous-based recombination and evidence for subtelomeric segmental duplications in 1p36 rearrangements.

    PubMed

    D'Angelo, Carla S; Gajecka, Marzena; Kim, Chong A; Gentles, Andrew J; Glotzbach, Caron D; Shaffer, Lisa G; Koiffmann, Célia P

    2009-06-01

    The mechanisms involved in the formation of subtelomeric rearrangements are now beginning to be elucidated. Breakpoint sequencing analysis of 1p36 rearrangements has made important contributions to this line of inquiry. Despite the unique architecture of segmental duplications inherent to human subtelomeres, no common mechanism has been identified thus far and different nonexclusive recombination-repair mechanisms seem to predominate. In order to gain further insights into the mechanisms of chromosome breakage, repair, and stabilization mediating subtelomeric rearrangements in humans, we investigated the constitutional rearrangements of 1p36. Cloning of the breakpoint junctions in a complex rearrangement and three non-reciprocal translocations revealed similarities at the junctions, such as microhomology of up to three nucleotides, along with no significant sequence identity in close proximity to the breakpoint regions. All the breakpoints appeared to be unique and their occurrence was limited to non-repetitive, unique DNA sequences. Several recombination- or cleavage-associated motifs that may promote non-homologous recombination were observed in close proximity to the junctions. We conclude that NHEJ is likely the mechanism of DNA repair that generates these rearrangements. Additionally, two apparently pure terminal deletions were also investigated, and the refinement of the breakpoint regions identified two distinct genomic intervals ~25-kb apart, each containing a series of 1p36 specific segmental duplications with 90-98% identity. Segmental duplications can serve as substrates for ectopic homologous recombination or stimulate genomic rearrangements. PMID:19271239

  16. RAP1GA1: A candidate tumor suppressor locus in 1p36.1

    SciTech Connect

    Ranade, K.; Hussussian, C.J.; Higgins, P.

    1994-09-01

    The rap1/Krev-1 gene (RAP1A) encodes a p21-related protein that suppresses transformation by activated p21{sup ras}. The GTPase activating protein (GAP) gene for p21{sup rap1A} (RAP1GA1) has recently been assigned to chromosome 1p36.1-p35, a region of the genome that is frequently involved in deletions and rearrangements in several different tumors including breast, colon and hepatocellular carcinomas, melanoma, and neuroblastoma. GAP genes negatively regulate the activity of p21 proteins by catalyzing the conversion of the active GTP-bound forms to the inactive GDP-bound forms. The physiological function of p21{sup rap1A}-GAP makes it a strong candidate as a tumor suppressor gene that may have a role in the development of one or more of these malignancies. We have refined the localization of RAP1GA1 by linkage analysis with a highly informative (CA){sub n} repeat contained within the gene, and demonstrated that it is within the minimal deleted region for breast and colon carcinomas, and that it is excluded from the minimally deleted region in melanoma and neuroblastoma. Genetic mapping in the mouse demonstrated that Rap1ga1 is located {approximately}10 cM proximal to Pnd and therefore maps within the interval containing the modifier of Min gene (Mom-1) and the plasmocytoma susceptibility locus (Pcts). The human RAP1GA1 gene contains at least 27 exons. The coding region contains 22 exons, and there are at least five 5{prime}-UT exons that are assembled in a complex pattern of alternative splicing in different tissues. The localization of RAP1GA1 makes it a very strong candidate for a role as a modifier gene involved in the common secondary abnormalities involving 1p36 in several different carcinomas. The potential role of RAP1GA1 in these malignancies is currently being investigated by sequence analysis of breast and colon carcinomas with loss of heterozygosity in 1p36.

  17. Genetics Home Reference: 1p36 deletion syndrome

    MedlinePlus

    ... 1p36, and clinical characterization of the syndrome. Am J Hum Genet. 2003 May;72(5):1200-12. Epub 2003 Apr 8. Citation on PubMed or Free article on PubMed Central Lahortiga I, Vázquez I, Belloni E, Román JP, Gasparini P, Novo FJ, Zudaire I, Pelicci PG, Hernández JM, Calasanz ...

  18. Clinical presentation of two β-thalassemic Indian patients with 1p36 deletion syndrome: Case report

    PubMed Central

    De, Puspal; Chatterjee, Tridip; Chakravarty, Sudipa; Chakravarty, Amit

    2014-01-01

    Here, we present two thalassemic patients (one male and one female), having unusual clinical phenotypes. Both had mental retardation in which one was associated with microcephaly and other had congenital cataract. They were referred to our institute for clinical evaluation and cytogenetic testing. Both patients were tested for presence of abnormal hemoglobin by high performance liquid chromatography and found to be thalassemic. Their β-globin mutation was also determined by amplification refractory mutation system-polymerase chain reaction. The male patient was found to have intervening sequence 1-5 (G-C)/+, indicating β-thalassemia trait and the female was found to have Cod 26 (G-A)/IVS 1-5 (G-C), indicating hemoglobin E-β thalassemia. Their cytogenetic analysis of blood lymphocytes were studied with high-resolution GTG-banding analysis by using chromosome profiling (Cyto-vision software 3.6) on their chromosomes. Results revealed 46,XY,del(1)(p36.21) in the male and 46,XX,del(1)(p36.3) in the female. Their genotype variation showed (based on genome browser) significant gene loss which probably leads to marked phenotype variation. We believe, thalassemia with mental retardation associated with microcephaly and congenital cataract, both having loss in chromosome 1, p36 position, is reported probably first time from India. This report will definitely enlighten all concerns and add to the information in growing literature.

  19. Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas.

    PubMed

    Martin-Guerrero, Idoia; Salaverria, Itziar; Burkhardt, Birgit; Szczepanowski, Monika; Baudis, Michael; Bens, Susanne; de Leval, Laurence; Garcia-Orad, Africa; Horn, Heike; Lisfeld, Jasmin; Pellissery, Shoji; Klapper, Wolfram; Oschlies, Ilske; Siebert, Reiner

    2013-08-01

    Pediatric follicular lymphoma is a rare disease that differs genetically and clinically from its adult counterpart. With the exception of pediatric follicular lymphoma with IRF4-translocation, the genetic events associated with these lymphomas have not yet been defined. We applied array-comparative genomic hybridization and molecular inversion probe assay analyses to formalin-fixed paraffin-embedded tissues from 18 patients aged 18 years and under with IRF4 translocation negative follicular lymphoma. All evaluable cases lacked t(14;18). Only 6 of 16 evaluable cases displayed chromosomal imbalances with gains or amplifications of 6pter-p24.3 (including IRF4) and deletion and copy number neutral-loss of heterozygosity in 1p36 (including TNFRSF14) being most frequent. Sequencing of TNFRSF14 located in the minimal region of loss in 1p36.32 showed nine mutations in 7 cases from our series. Two subsets of pediatric follicular lymphoma were delineated according to the presence of molecular alterations, one with genomic aberrations associated with higher grade and/or diffuse large B-cell lymphoma component and more widespread disease, and another one lacking genetic alterations associated with more limited disease. PMID:23445872

  20. Monosomy 1p36.31-33{yields}pter due to a paternal reciprocal translocation: Prognostic significance of FISH analysis

    SciTech Connect

    Blennow, E.; Bui, The-Hung; Wallin, A.

    1996-10-02

    A rare monosomy 1p36.31-33{r_arrow}pter was found in a child with physical anomalies, psycho-motor retardation, and seizures. Cytogenetic investigation suggested an unbalanced translocation between 1p and an acrocentric chromosome, but the rearrangement was difficult to assess accurately using conventional chromosome banding techniques. The half-cryptic translocation was further characterized using fluorescence in situ hybridization, and the aberrant chromosome 1 was shown to be a derivate of a paternal reciprocal translocation t(1;15)(p36.31-33;p11.2-12). The breakpoints on chromosome 1 and 15 were defined in detail using locus specific probes. The rearrangement did not include the region on chromosome 1p which previously has been suggested to predispose to the development of neuroblastoma in a case with a constitutional translocation. At 3 6/12 years, the patient has no clinical signs of this disease, which illustrates the prognostic significance of this investigation. 30 refs., 4 figs., 1 tab.

  1. Fine Mapping of the 1p36 Deletion Syndrome Identifies Mutation of PRDM16 as a Cause of Cardiomyopathy

    PubMed Central

    Arndt, Anne-Karin; Schafer, Sebastian; Drenckhahn, Jorg-Detlef; Sabeh, M. Khaled; Plovie, Eva R.; Caliebe, Almuth; Klopocki, Eva; Musso, Gabriel; Werdich, Andreas A.; Kalwa, Hermann; Heinig, Matthias; Padera, Robert F.; Wassilew, Katharina; Bluhm, Julia; Harnack, Christine; Martitz, Janine; Barton, Paul J.; Greutmann, Matthias; Berger, Felix; Hubner, Norbert; Siebert, Reiner; Kramer, Hans-Heiner; Cook, Stuart A.; MacRae, Calum A.; Klaassen, Sabine

    2013-01-01

    Deletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM). With our own data and publically available data from array comparative genomic hybridization (aCGH), we identified a minimal deletion for the cardiomyopathy associated with 1p36del syndrome that included only the terminal 14 exons of the transcription factor PRDM16 (PR domain containing 16), a gene that had previously been shown to direct brown fat determination and differentiation. Resequencing of PRDM16 in a cohort of 75 nonsyndromic individuals with LVNC detected three mutations, including one truncation mutant, one frameshift null mutation, and a single missense mutant. In addition, in a series of cardiac biopsies from 131 individuals with DCM, we found 5 individuals with 4 previously unreported nonsynonymous variants in the coding region of PRDM16. None of the PRDM16 mutations identified were observed in more than 6,400 controls. PRDM16 has not previously been associated with cardiac disease but is localized in the nuclei of cardiomyocytes throughout murine and human development and in the adult heart. Modeling of PRDM16 haploinsufficiency and a human truncation mutant in zebrafish resulted in both contractile dysfunction and partial uncoupling of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM. PMID:23768516

  2. Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy.

    PubMed

    Arndt, Anne-Karin; Schafer, Sebastian; Drenckhahn, Jorg-Detlef; Sabeh, M Khaled; Plovie, Eva R; Caliebe, Almuth; Klopocki, Eva; Musso, Gabriel; Werdich, Andreas A; Kalwa, Hermann; Heinig, Matthias; Padera, Robert F; Wassilew, Katharina; Bluhm, Julia; Harnack, Christine; Martitz, Janine; Barton, Paul J; Greutmann, Matthias; Berger, Felix; Hubner, Norbert; Siebert, Reiner; Kramer, Hans-Heiner; Cook, Stuart A; MacRae, Calum A; Klaassen, Sabine

    2013-07-11

    Deletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM). With our own data and publically available data from array comparative genomic hybridization (aCGH), we identified a minimal deletion for the cardiomyopathy associated with 1p36del syndrome that included only the terminal 14 exons of the transcription factor PRDM16 (PR domain containing 16), a gene that had previously been shown to direct brown fat determination and differentiation. Resequencing of PRDM16 in a cohort of 75 nonsyndromic individuals with LVNC detected three mutations, including one truncation mutant, one frameshift null mutation, and a single missense mutant. In addition, in a series of cardiac biopsies from 131 individuals with DCM, we found 5 individuals with 4 previously unreported nonsynonymous variants in the coding region of PRDM16. None of the PRDM16 mutations identified were observed in more than 6,400 controls. PRDM16 has not previously been associated with cardiac disease but is localized in the nuclei of cardiomyocytes throughout murine and human development and in the adult heart. Modeling of PRDM16 haploinsufficiency and a human truncation mutant in zebrafish resulted in both contractile dysfunction and partial uncoupling of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM. PMID:23768516

  3. Detection of amplified or deleted chromosomal regions

    DOEpatents

    Stokke, T.; Pinkel, D.; Gray, J.W.

    1995-12-05

    The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20. 3 figs.

  4. Detection of amplified or deleted chromosomal regions

    DOEpatents

    Stokke, Trond; Pinkel, Daniel; Gray, Joe W.

    1995-01-01

    The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

  5. Detection Of Amplified Or Deleted Chromosomal Regions

    DOEpatents

    Stokke, Trond , Pinkel, Daniel , Gray, Joe W.

    1997-05-27

    The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

  6. Identification of 1p36 deletion syndrome in patients with facial dysmorphism and developmental delay

    PubMed Central

    Seo, Go Hun; Kim, Ja Hye; Cho, Ja Hyang; Kim, Gu-Hwan; Seo, Eul-Ju; Lee, Beom Hee; Choi, Jin-Ho

    2016-01-01

    Purpose The 1p36 deletion syndrome is a microdeletion syndrome characterized by developmental delays/intellectual disability, craniofacial dysmorphism, and other congenital anomalies. To date, many cases of this syndrome have been reported worldwide. However, cases with this syndrome have not been reported in Korean populations anywhere. This study was performed to report the clinical and molecular characteristics of five Korean patients with the 1p36 deletion syndrome. Methods The clinical characteristics of the 5 patients were reviewed. Karyotyping and multiplex ligation-dependent probe amplification (MLPA) analyses were performed for genetic diagnoses. Results All 5 patients had typical dysmorphic features including frontal bossing, flat right parietal bone, low-set ears, straight eyebrows, down-slanting palpebral fissure, hypotelorism, flat nasal roots, midface hypoplasia, pointed chins, small lips, and variable degrees of developmental delay. Each patient had multiple and variable anomalies such as a congenital heart defect including ventricular septal defect, atrial septal defect, and patent duct arteriosus, ventriculomegaly, cryptorchism, or hearing loss. Karyotyping revealed the 1p36 deletion in only 1 patient, although it was confirmed in all 5 patients by MLPA analyses. Conclusion All the patients had the typical features of 1p36 deletion. These hallmarks can be used to identify other patients with this condition in their early years in order to provide more appropriate care. PMID:26893599

  7. Role of Evaluating MGMT Status and 1p36 Deletion in Radiosurgery-Induced Anaplastic Ependymoma That Rapidly and Completely Resolved by Temozolomide Alone: Case Report and Review of the Literature

    PubMed Central

    Hirono, Seiichiro; Iwadate, Yasuo; Kambe, Michiyo; Hiwasa, Takaki; Takiguchi, Masaki; Nakatani, Yukio; Saeki, Naokatsu

    2015-01-01

    Stereotactic gamma knife surgery (GKS)-induced brain tumors are extremely rare, and no ependymal tumors induced by GKS have been reported. Therefore, little is known about their clinical, pathologic, and genetic features. In addition, a regimen of adjuvant chemotherapy for anaplastic ependymoma (AE) has not been established. A 77-year-old man presented with a gait disturbance and left-side cerebellar ataxia more than 19 years after GKS performed for a cerebellar arteriovenous malformation. Imaging studies demonstrated an enhancing mass in the irradiated field with signs of intraventricular dissemination. Surgical resection confirmed the diagnosis of AE. Temozolomide (TMZ) was administrated postoperatively because the methylated promoter region of O6-methylguanine-DNA methyltransferase (MGMT) and 1p36 deletion were observed. Surprisingly, images 16 days after TMZ initiation demonstrated a complete resolution of the residual tumor that was maintained after three cycles of TMZ. This first case report of GKS-induced AE emphasizes the importance of genetic evaluation of MGMT and chromosomal deletion of 1p36 that are not commonly performed in primary ependymal tumors. In addition, it is speculated that a GKS-induced tumor may have a different genetic background compared with the primary tumor because the pathogenesis of the tumors differed. PMID:26251808

  8. Role of Evaluating MGMT Status and 1p36 Deletion in Radiosurgery-Induced Anaplastic Ependymoma That Rapidly and Completely Resolved by Temozolomide Alone: Case Report and Review of the Literature.

    PubMed

    Hirono, Seiichiro; Iwadate, Yasuo; Kambe, Michiyo; Hiwasa, Takaki; Takiguchi, Masaki; Nakatani, Yukio; Saeki, Naokatsu

    2015-07-01

    Stereotactic gamma knife surgery (GKS)-induced brain tumors are extremely rare, and no ependymal tumors induced by GKS have been reported. Therefore, little is known about their clinical, pathologic, and genetic features. In addition, a regimen of adjuvant chemotherapy for anaplastic ependymoma (AE) has not been established. A 77-year-old man presented with a gait disturbance and left-side cerebellar ataxia more than 19 years after GKS performed for a cerebellar arteriovenous malformation. Imaging studies demonstrated an enhancing mass in the irradiated field with signs of intraventricular dissemination. Surgical resection confirmed the diagnosis of AE. Temozolomide (TMZ) was administrated postoperatively because the methylated promoter region of O(6)-methylguanine-DNA methyltransferase (MGMT) and 1p36 deletion were observed. Surprisingly, images 16 days after TMZ initiation demonstrated a complete resolution of the residual tumor that was maintained after three cycles of TMZ. This first case report of GKS-induced AE emphasizes the importance of genetic evaluation of MGMT and chromosomal deletion of 1p36 that are not commonly performed in primary ependymal tumors. In addition, it is speculated that a GKS-induced tumor may have a different genetic background compared with the primary tumor because the pathogenesis of the tumors differed. PMID:26251808

  9. Accurate, Fast and Cost-Effective Diagnostic Test for Monosomy 1p36 Using Real-Time Quantitative PCR

    PubMed Central

    Cunha, Pricila da Silva; Pena, Heloisa B.; D'Angelo, Carla Sustek; Koiffmann, Celia P.; Rosenfeld, Jill A.; Shaffer, Lisa G.; Stofanko, Martin; Gonçalves-Dornelas, Higgor; Pena, Sérgio Danilo Junho

    2014-01-01

    Monosomy 1p36 is considered the most common subtelomeric deletion syndrome in humans and it accounts for 0.5–0.7% of all the cases of idiopathic intellectual disability. The molecular diagnosis is often made by microarray-based comparative genomic hybridization (aCGH), which has the drawback of being a high-cost technique. However, patients with classic monosomy 1p36 share some typical clinical characteristics that, together with its common prevalence, justify the development of a less expensive, targeted diagnostic method. In this study, we developed a simple, rapid, and inexpensive real-time quantitative PCR (qPCR) assay for targeted diagnosis of monosomy 1p36, easily accessible for low-budget laboratories in developing countries. For this, we have chosen two target genes which are deleted in the majority of patients with monosomy 1p36: PRKCZ and SKI. In total, 39 patients previously diagnosed with monosomy 1p36 by aCGH, fluorescent in situ hybridization (FISH), and/or multiplex ligation-dependent probe amplification (MLPA) all tested positive on our qPCR assay. By simultaneously using these two genes we have been able to detect 1p36 deletions with 100% sensitivity and 100% specificity. We conclude that qPCR of PRKCZ and SKI is a fast and accurate diagnostic test for monosomy 1p36, costing less than 10 US dollars in reagent costs. PMID:24839341

  10. The plasmacytoma resistance gene, Pctr2, delays the onset of tumorigenesis and resides in the telomeric region of chromosome 4.

    PubMed

    Mock, B A; Hartley, J; Le Tissier, P; Wax, J S; Potter, M

    1997-11-15

    Mouse plasmacytomas share pathogenetic features in common with both multiple myeloma and Burkitt's lymphoma in humans. Susceptibility to plasmacytoma induction by intraperitoneal pristane in mice is controlled by multiple genes. At least two of these genes reside on mouse chromosome 4 in regions of the genome sharing linkage homology with human chromosomes 9p21, 1p32, and 1p36. A series of congenic strains recombinant for regions of mouse chromosome 4 in the vicinity of the Pctr2 predisposition locus were created and typed for their tumor susceptibility/resistance phenotypes. These strains were derived by introgressively backcrossing alleles from resistant DBA/2 mice onto the susceptible BALB/cAnPt background. Six resistant and two susceptible strains were allelotyped for 10 genes and 49 random DNA markers to identify the smallest region of overlap in the resistant strains. These studies have determined that the Pctr2 locus resides in either a 500-kb interval proximal to Nppa, or in a 1- to 2-centiMorgan (cM) interval distal to Nppa. In these congenic strain analyses, the Nppa and Fv1 loci, in addition to genes within about 1 cM of these loci, have been excluded as candidates for the Pctr2 locus. A relevant locus that may reside in this interval is Rep2; it is associated with the efficiency of repairing X-ray induced DNA damage sustained during the G2 phase of the mitotic cycle. The Pctr2 locus acts in a codominant fashion. F1 hybrids between resistant and susceptible congenic strains exhibit a reduced tumor incidence and a significant delay in the onset of tumorigenesis. Identification and eventual cloning of the Pctr2 locus may assist in the identification of genes involved in many types of cancer showing aberrations in human chromosome 1p36. PMID:9354679

  11. Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations.

    PubMed

    Siddiqi, Imran N; Friedman, Julia; Barry-Holson, Keegan Q; Ma, Charles; Thodima, Venkata; Kang, Irene; Padmanabhan, Raghavendra; Dias, Lizalynn M; Kelly, Kevin R; Brynes, Russell K; Kamalakaran, Sitharthan; Houldsworth, Jane

    2016-06-01

    A predominantly diffuse growth pattern and CD23 co-expression are uncommon findings in nodal follicular lymphoma and can create diagnostic challenges. A single case series in 2009 (Katzenberger et al) proposed a unique morphologic variant of nodal follicular lymphoma, characterized by a predominantly diffuse architecture, lack of the t(14;18) IGH/BCL2 translocation, presence of 1p36 deletion, frequent inguinal lymph node involvement, CD23 co-expression, and low clinical stage. Other studies on CD23+ follicular lymphoma, while associating inguinal location, have not specifically described this architecture. In addition, no follow-up studies have correlated the histopathologic and cytogenetic/molecular features of these cases, and they remain a diagnostic problem. We identified 11 cases of diffuse, CD23+ follicular lymphoma with histopathologic features similar to those described by Katzenberger et al. Along with pertinent clinical information, we detail their histopathology, IGH/BCL2 translocation status, lymphoma-associated chromosomal gains/losses, and assessment of mutations in 220 lymphoma-associated genes by massively parallel sequencing. All cases showed a diffuse growth pattern around well- to ill-defined residual germinal centers, uniform CD23 expression, mixed centrocytic/centroblastic cytology, and expression of at least one germinal center marker. Ten of 11 involved inguinal lymph nodes, 5 solely. By fluorescence in situ hybridization analysis, the vast majority lacked IGH/BCL2 translocation (9/11). Deletion of 1p36 was observed in five cases and included TNFRSF14. Of the six cases lacking 1p36 deletion, TNFRSF14 mutations were identified in three, highlighting the strong association of 1p36/TNFRSF14 abnormalities with this follicular lymphoma variant. In addition, 9 of the 11 cases tested (82%) had STAT6 mutations and nuclear P-STAT6 expression was detectable in the mutated cases by immunohistochemistry. The proportion of STAT6 mutations is higher than

  12. The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor.

    PubMed

    Schlisio, Susanne; Kenchappa, Rajappa S; Vredeveld, Liesbeth C W; George, Rani E; Stewart, Rodney; Greulich, Heidi; Shahriari, Kristina; Nguyen, Nguyen V; Pigny, Pascal; Dahia, Patricia L; Pomeroy, Scott L; Maris, John M; Look, A Thomas; Meyerson, Matthew; Peeper, Daniel S; Carter, Bruce D; Kaelin, William G

    2008-04-01

    VHL, NF-1, c-Ret, and Succinate Dehydrogenase Subunits B and D act on a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells and requires the EglN3 prolyl hydroxylase as a downstream effector. Germline mutations of these genes cause familial pheochromocytoma and other neural crest-derived tumors. Using an unbiased shRNA screen we found that the kinesin KIF1Bbeta acts downstream from EglN3 and is both necessary and sufficient for neuronal apoptosis when NGF becomes limiting. KIF1Bbeta maps to chromosome 1p36.2, which is frequently deleted in neural crest-derived tumors including neuroblastomas. We identified inherited loss-of-function KIF1Bbeta missense mutations in neuroblastomas and pheochromocytomas and an acquired loss-of-function mutation in a medulloblastoma, arguing that KIF1Bbeta is a pathogenic target of these deletions. PMID:18334619

  13. CHROMOSOMAL LOCATION AND GENE PAUCITY IN THE MALE SPECIFIC REGION ON PAPAYA Y CHROMOSOME

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sex chromosomes in flowering plants evolved recently and many of them remain homomorphic, including those in papaya. We investigated the chromosomal location of papaya’s small male specific region of the hermaphrodite Y (Yh) chromosome (MSY) and its genomic features. We conducted chromosome fluoresc...

  14. 576 kb deletion in 1p36.33-p36.32 containing SKI is associated with limb malformation, congenital heart disease and epilepsy.

    PubMed

    Zhu, Xin; Zhang, Yi; Wang, Jian; Yang, Jin-Fu; Yang, Yi-Feng; Tan, Zhi-Ping

    2013-10-10

    1p36 deletion (monosomy 1p36) is one of the most common terminal deletions observed in humans, characterized by special facial features, mental retardation, heart defects, development delay and epilepsy. Previously, we reported molecular findings in patients with limb, congenital heart disease (CHD) and other malformations with SNP-array. In a syndromic patient of the same cohort, we detected a small deletion of 1p36.33-p36.32 containing SKI (Sloan-Kettering Institute protooncoprotein). Recently, dominant mutations in SKI were identified to be correlated with Shprintzen-Goldberg syndrome. Retrospective examination revealed this patient with limb malformations, CHD, epilepsy and mild development delay. Together with previous reports, our study suggests that the 1p36.33-1p36.32 deletion encompassing SKI may represents a previous undescribed microdeletion disorder. PMID:23892090

  15. Genetic, physical, and comparative map of the subtelomeric region of mouse Chromosome 4

    PubMed Central

    Li, Xia; Bachmanov, Alexander A.; Li, Shanru; Chen, Zhenyu; Tordoff, Michael G.; Beauchamp, Gary K.; de Jong, Pieter J.; Wu, Chenyan; Chen, Lianchun; West, David B.; Ross, David A.; Ohmen, Jeffery D.; Reed, Danielle R.

    2007-01-01

    The subtelomeric region of mouse chromosome (Chr) 4 harbors loci with effects on behavior, development, and disease susceptibility. Regions near the telomeres are more difficult to map and characterize than other areas because of the unique features of subtelomeric DNA. As a result of these problems, the available mapping information for this part of mouse Chr 4 was insufficient to pursue candidate gene evaluation. Therefore, we sought to characterize the area in greater detail by creating a comprehensive genetic, physical, and comparative map. We constructed a genetic map that contained 30 markers and covered 13.3 cM; then we created a 1.2-Mb sequence-ready BAC contig, representing a 5.1-cM area, and sequenced a 246-kb mouse BAC from this contig. The resulting sequence, as well as approximately 40 kb of previously deposited genomic sequence, yielded a total of 284 kb of sequence, which contained over 20 putative genes. These putative genes were confirmed by matching ESTs or cDNA in the public databases to the genomic sequence and/or by direct sequencing of cDNA. Comparative genome sequence analysis demonstrated conserved synteny between the mouse and the human genomes (1p36.3). DNA from two strains of mice (C57BL/6ByJ and 129P3/J) was sequenced to detect single nucleotide polymorphisms (SNPs). The frequency of SNPs in this region was more than threefold higher than the genome-wide average for comparable mouse strains (129/Sv and C57BL/6J). The resulting SNP map, in conjunction with the sequence annotation and with physical and genetic maps, provides a detailed description of this gene-rich region. These data will facilitate genetic and comparative mapping studies and identification of a large number of novel candidate genes for the trait loci mapped to this region. PMID:11773963

  16. Anhidrotic ectodermal dysplasia gene region cloned in yeast artificial chromosomes

    SciTech Connect

    Kere, J. |; Grzeschik, K.H.; Limon, J.; Gremaud, M.; Schlessinger, D.; De La Chapelle, A.

    1993-05-01

    Anhidrotic ectodermal dysplasia (EDA), an X-chromosomal recessive disorder, is expressed in a few females with chromosomal translocations involving bands Xq12-q13. Using available DNA markers from the region and somatic cell hybrids the authors mapped the X-chromosomal breakpoints in two such translocations. The breakpoints were further mapped within a yeast artificial chromosome contig constructed by chromosome walking techniques. Genomic DNA markers that map between the two translocation breakpoints were recovered representing putative portions of the EDA gene. 32 refs., 3 figs., 1 tab.

  17. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  18. Regional mapping of loci from human chromosome 2q to sheep chromosome 2q

    SciTech Connect

    Ansari, H.A.; Pearce, P.D.; Maher, D.W.; Malcolm, A.A.; Wood, N.J.; Phua, S.H.; Broad, T.E. )

    1994-03-01

    The human chromosome 2q loci, fibronectin 1 (FN1), the [alpha]1 chain of type III collagen (COL3A1), and the [delta] subunit of the muscle acetylcholine receptor (CHRND) have been regionally assigned to sheep chromosome 2q by in situ hybridization. COL3A1 is pericentromeric (2q12-q21), while FN1 and CHRND are in the subterminal region at 2q41-q44 and 2q42-qter, respectively. The mapping of FN1 assigns the sheep synthenic group U11, which contains FN1, villin 1 (VIL1), isocitrate dehydrogenase 1 (IDH1), and [gamma] subunit of the muscle acetylcholine receptor (CHRNG), to sheep chromosome 2q. Inhibin-[alpha] (INHA) is also assigned to sheep chromosome 2q as FN1 and INHA compose sheep linkage group 3. These seven loci are members of a conserved chromosomal segment in human, mouse, and sheep. 23 refs., 2 figs., 1 tab.

  19. Chemical and conformational changes in chromosome regions being actively transcribed.

    PubMed Central

    Pagés, M; Alonso, C

    1978-01-01

    U.V. microspectrophotometry has been used to calculate quantities of nucleic acids and proteins of complete polytene chromosomal sets and specific regions of these chromosomes. It has been found that in chromosomes the ratio of DNA to proteins is approximately 1:4. This ratio however changes when specific regions are compared. The average ratio of DNA to proteins in a puffed region (2-48B4C5) increases to 1:16 in contrast to 1:6 from the same region but in non puffed state. At the same time the RNA quantity increases by a factor of 2. thermal denaturation profiles of formaldehyde fixed chromosomes show that the Tm of this region in puffed and non puffed state differ by 10 degrees C. Moreover these profiles suggest that a large fraction of histone-bound DNA is destabilized during puffing. PMID:634798

  20. Regional Control of Nondisjunction of the B Chromosome in Maize

    PubMed Central

    Lin, Bor-Yaw

    1978-01-01

    Control of nondisjunction in the maize B chromosome was studied using a set of B-10 translocations. The study focused on the possible effect of the proximal region of the B long arm. The experimental procedure utilized a combination of a 10B chromosome from one translocation with a B10 from another translocation. The breakpoints of the two translocations were so located that combination of the two elements created a deletion in the proximal region of the B chromosome, but no deletion in chromosome 10. Two different types of deletions were established; one involved a portion of the euchromatic region and the other the entire heterochromatic portion comprising the distal half of the B long arm, except for the small euchromatic tip. Deletion of the heterochromatic portion did not exert any effect on nondisjunction. Deletions of different portions of the euchromatic region produce different responses. Some deletions resulted in typical B nondisjunctional activity; others resulted in the disappearance of this activity. It is concluded that a region within the euchromatic portion of the chromosome is critical for the nondisjunction of B chromosomes. Among 22 translocations with breakpoints in the euchromatic regions, three were proximal to the critical region, 16 were distal and the position of three others was not determined. PMID:17248872

  1. The X chromosome of monotremes shares a highly conserved region with the eutherian and marsupial X chromosomes despite the absence of X chromosome inactivation

    SciTech Connect

    Watson, J.M.; Spencer, J.A.; Graves, J.A.M. ); Riggs, A.D. )

    1990-09-01

    Eight genes, located on the long arm of the human X chromosome and present on the marsupial X chromosome, were mapped by in situ hybridization to the chromosomes of the platypus Ornithorhynchus anatinus, one of the three species of monotreme mammals. All were located on the X chromosome. The authors conclude that the long arm of the human X chromosome represents a highly conserved region that formed part of the X chromosome in a mammalian ancestor at least 150 million years ago. Since three of these genes are located on the long arm of the platypus X chromosome, which is G-band homologous to the Y chromosome and apparently exempt from X chromosome inactivation, the conservation of this region has evidently not depended on isolation by X-Y chromosome differentiation and X chromosome inactivation.

  2. A syntenic region conserved from fish to Mammalian x chromosome.

    PubMed

    Guan, Guijun; Yi, Meisheng; Kobayashi, Tohru; Hong, Yunhan; Nagahama, Yoshitaka

    2014-01-01

    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. PMID:25506037

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

    SciTech Connect

    Trent, J.M.; Guan, X.Y.; Zang, J.; Meltzer, P.S. )

    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.

  4. Chromosome region-specific libraries for human genome analysis

    SciTech Connect

    Kao, Fa-Ten.

    1992-08-01

    During the grant period progress has been made in the successful demonstration of regional mapping of microclones derived from microdissection libraries; successful demonstration of the feasibility of converting microclones with short inserts into yeast artificial chromosome clones with very large inserts for high resolution physical mapping of the dissected region; Successful demonstration of the usefulness of region-specific microclones to isolate region-specific cDNA clones as candidate genes to facilitate search for the crucial genes underlying genetic diseases assigned to the dissected region; and the successful construction of four region-specific microdissection libraries for human chromosome 2, including 2q35-q37, 2q33-q35, 2p23-p25 and 2p2l-p23. The 2q35-q37 library has been characterized in detail. The characterization of the other three libraries is in progress. These region-specific microdissection libraries and the unique sequence microclones derived from the libraries will be valuable resources for investigators engaged in high resolution physical mapping and isolation of disease-related genes residing in these chromosomal regions.

  5. [Identification of chromosomal aberration in esophageal cancer cells by mixed BAC DNA probes of chromosome arms and regions].

    PubMed

    Jiajie, Hao; Chunli, Wang; Wenyue, Gu; Xiaoyu, Cheng; Yu, Zhang; Xin, Xu; Yan, Cai; Mingrong, Wang

    2014-06-01

    Chromosomal aberration is an important genetic feature of malignant tumor cells. This study aimed to clarify whether BAC DNA could be used to identify chromosome region and arm alterations. For each chromosome region, five to ten 1 Mb BAC DNA clones were selected to construct mixed BAC DNA clones for the particular region. All of the mixed clones from regions which could cover the whole chromosome arm were then mixed to construct mixed BAC DNA clones for the arms. Mixed BAC DNA probes of arms and regions were labeled by degenerate oligonucleotide primed PCR (DOP-PCR) and Nick translation techniques, respectively. The specificities of these probes were validated by fluorescence in situ hybridization (FISH) on the metaphase chromosomes of normal human peripheral blood lymphocytes. FISH with arm-specific mixed BAC DNA probes showed that chromosomal rearrangements and involved chromosome arms were confirmed in several esophageal cancer cells. By using region-specific mixed probes, the breakpoint on 1q from the derivative chromosome t(1q;7q) was identified in 1q32-q41 in esophageal KYSE140 cells. In conclusion, we established an effective labeling method for 1 Mb BAC DNA mixed clone probes, and chromosome arm and region rearrangements could be identified in several esophageal cancer cells by using these probes. Our study provides a more precise method for identification of chromosomal aberration by M-FISH, and the established method may also be applied to the karyotype analysis of hematological malignancies and prenatal diagnosis. PMID:24929514

  6. Chromosome

    MedlinePlus

    ... if you are born a boy or a girl (your gender). They are called sex chromosomes: Females have 2 X chromosomes. Males have 1 X and 1 Y chromosome. The mother gives an X chromosome to the ... baby is a girl or a boy. The remaining chromosomes are called ...

  7. Chromosome

    MedlinePlus

    ... genes . It is the building block of the human body. Chromosomes also contain proteins that help DNA exist ... come in pairs. Normally, each cell in the human body has 23 pairs of chromosomes (46 total chromosomes). ...

  8. Chromosome localization analysis of genes strongly expressed in human visceral adipose tissue.

    PubMed

    Yang, Yi-Sheng; Song, Huai-Dong; Shi, Wen-Jing; Hu, Ren-Ming; Han, Ze-Guang; Chen, Jia-Lun

    2002-06-01

    To understand fully the physiologic functions of visceral adipose tissue and to provide a basis for the identification of novel genes related to obesity and insulin resistance, the gene expression profiling of human visceral adipose tissue was established by using cDNA array. The characterization and chromosome localization of 400 expressed sequence tags (ESTs) strongly expressed in visceral adipose tissue were analyzed by searching PubMed, UniGene, the Human Genome Draft Database, and Location Data Base. Two hundred eighty-nine clones were classified into known genes among the 400 ESTs strongly expressed in the tissue. Among them, <20% have been previously reported to be expressed in adipose tissue. The chromosome localization of 389 ESTs strongly expressed in visceral adipose tissue showed that their relative abundance was significantly increased on chromosomes 1, 16, 19, 20, and 22 compared with the expected distribution of the same number of random genes. The intrachromosome distribution of the genes strongly expressed in visceral adipose tissue was concentrated in certain regions, such as 1p36.2-1p36.3, 6p21.3-6p22.1, 19p13.3 and 19q13.1. Among them, the region of 1p36.2-1p36.3 appeared to be specific for visceral adipose tissue. Interestingly, some genes playing an important role in the pathogenesis of insulin signal transduction and adipocyte differentiation, such as tumor necrosis factor-alpha and its receptors; CCAAT/enhancer-binding proteina; and phosphoinositide-3-kinase, regulatory subunit, polypeptide 2 (p85beta), were also localized in the concentrated regions, which may provide clues to identifying novel genes closely related to adipocyte function with potential pathophysiologic implications. PMID:12166625

  9. Primary Cutaneous Follicle Center Lymphomas Expressing BCL2 Protein Frequently Harbor BCL2 Gene Break and May Present 1p36 Deletion: A Study of 20 Cases.

    PubMed

    Szablewski, Vanessa; Ingen-Housz-Oro, Saskia; Baia, Maryse; Delfau-Larue, Marie-Helene; Copie-Bergman, Christiane; Ortonne, Nicolas

    2016-01-01

    The classification of cutaneous follicular lymphoma (CFL) into primary cutaneous follicle center lymphoma (PCFCL) or secondary cutaneous follicular lymphoma (SCFL) is challenging. SCFL is suspected when tumor cells express BCL2 protein, reflecting a BCL2 translocation. However, BCL2 expression is difficult to assess in CFLs because of numerous BCL2+ reactive T cells. To investigate these issues and to further characterize PCFCL, we studied a series of 25 CFLs without any extracutaneous disease at diagnosis, selected on the basis of BCL2 protein expression using 2 BCL2 antibodies (clones 124 and E17) and BOB1/BCL2 double immunostaining. All cases were studied using interphase fluorescence in situ hybridization with BCL2, BCL6, IGH, IGK, IGL breakapart, IGH-BCL2 fusion, and 1p36/1q25 dual-color probes. Nineteen CFLs were BCL2 positive, and 6 were negative. After a medium follow-up of 24 (6 to 96) months, 5 cases were reclassified as SCFL and were excluded from a part of our analyses. Among BCL2+ PCFCLs, 60% (9/15) demonstrated a BCL2 break. BCL2-break-positive cases had a tendency to occur in the head and neck and showed the classical phenotype of nodal follicular lymphoma (CD10+, BCL6+, BCL2+, STMN+) compared with BCL2-break-negative PCFCLs. Del 1p36 was observed in 1 PCFCL. No significant clinical differences were observed between BCL2+ or BCL2- PCFCL. In conclusion, we show that a subset of PCFCLs harbor similar genetic alterations, as observed in nodal follicular lymphomas, including BCL2 breaks and 1p36 deletion. As BCL2 protein expression is usually associated with the presence of a BCL2 translocation, fluorescence in situ hybridization should be performed to confirm this hypothesis. PMID:26658664

  10. A Cytogenetic Analysis of Chromosomal Region 31 of Drosophila Melanogaster

    PubMed Central

    Clegg, N. J.; Whitehead, I. P.; Brock, J. K.; Sinclair, D. A.; Mottus, R.; Stromotich, G.; Harrington, M. J.; Grigliatti, T. A.

    1993-01-01

    Cytogenetic region 31 of the second chromosome of Drosophila melanogaster was screened for recessive lethal mutations. One hundred and thirty nine new recessive lethal alleles were isolated that fail to complement Df(2L)J2 (31A-32A). These new alleles, combined with preexisting mutations in the region, define 52 complementation groups, 35 of which have not previously been described. Among the new mutations were alleles of the cdc2 and mfs(2)31 genes. Six new deficiencies were also isolated and characterized identifying 16 deficiency subintervals within region 31. The new deficiencies were used to further localize three loci believed to encode non-histone chromosomal proteins. Suvar(2)1/Su(var)214, a dominant suppressor of position-effect variegation (PEV), maps to 31A-B, while the recessive suppressors of PEV mfs(2)31 and wdl were localized to regions 31E and 31F-32A, respectively. In addition, the cytological position of several mutations that interact with heterochromatin were more precisely defined. PMID:8514131

  11. GENOME-WIDE SCAN FOR SERUM GHRELIN DETECTS LINKAGE ON CHROMOSOME 1P36 IN HISPANIC CHILDREN: RESULTS FROM THE VIVA LA FAMILIA STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was conducted to investigate genetic influence on serum ghrelin and its relationship with adiposity-related phenotypes in Hispanic children (n = 1030) from the Viva La Familia study (VFS). Anthropometric measurements and levels of serum ghrelin were estimated and genetic analyses conducte...

  12. Genome-wide scan for plasma ghrelin detects linkage on chromosome 1p36 in Hispanic children: Results from the Viva La Familia study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disorders in energy homeostasis are believed to be among the key contributing factors in the development of obesity. The rapid increase in the prevalence of obesity, particularly in children, is a major public health issue. Ghrelin is a brain-gut peptide with an important role in the regulation of e...

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

    PubMed

    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. PMID:25966582

  14. Amplifications of chromosomal region 20q13 as a prognostic indicator in breast cancer

    DOEpatents

    Gray, Joe W.; Collins, Colin; Pinkel, Daniel; Kallioniemi, Olli-Pekka; Tanner, Minna M.

    1998-01-01

    The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

  15. Amplifications of chromosomal region 20q13 as a prognostic indicator breast cancer

    DOEpatents

    Gray, Joe W.; Collins, Colin; Pinkel, Daniel; Kallioniemi, Olli-Pekka; Tanner, Minna M.

    2001-01-01

    The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.

  16. Chromosome region-specific libraries for human genome analysis

    SciTech Connect

    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.

  17. Identification of chromosomal regions involved in decapentaplegic function in Drosophila.

    PubMed Central

    Nicholls, R E; Gelbart, W M

    1998-01-01

    Signaling molecules of the transforming growth factor beta (TGF-beta) family contribute to numerous developmental processes in a variety of organisms. However, our understanding of the mechanisms which regulate the activity of and mediate the response to TGF-beta family members remains incomplete. The product of the Drosophila decapentaplegic (dpp) locus is a well-characterized member of this family. We have taken a genetic approach to identify factors required for TGF-beta function in Drosophila by testing for genetic interactions between mutant alleles of dpp and a collection of chromosomal deficiencies. Our survey identified two deficiencies that act as maternal enhancers of recessive embryonic lethal alleles of dpp. The enhanced individuals die with weakly ventralized phenotypes. These phenotypes are consistent with a mechanism whereby the deficiencies deplete two maternally provided factors required for dpp's role in embryonic dorsal-ventral pattern formation. One of these deficiencies also appears to delete a factor required for dpp function in wing vein formation. These deficiencies remove material from the 54F-55A and 66B-66C polytene chromosomal regions, respectively. As neither of these regions has been previously implicated in dpp function, we propose that each of the deficiencies removes a novel factor or factors required for dpp function. PMID:9584097

  18. Frequent hemizygous deletion at 1p36 and hypermethylation downregulate RUNX3 expression in human lung cancer cell lines.

    PubMed

    Yanada, Masashi; Yaoi, Takeshi; Shimada, Junichi; Sakakura, Chouhei; Nishimura, Motohiro; Ito, Kazuhiro; Terauchi, Kunihiko; Nishiyama, Katsuhiko; Itoh, Kyoko; Fushiki, Shinji

    2005-10-01

    Runt-related transcription factor 3 (RUNX3) has been recognized as a tumor suppressor gene in gastric cancer because its expression level was reduced or disappeared due to epigenetic changes. To evaluate the usefulness of the RUNX3 gene as a biomarker of lung cancer, we have analyzed the expression of the RUNX3 gene in 15 lung cancer cell lines by real-time reverse transcription-polymerase chain reaction (RT-PCR), and demonstrated that RUNX3 gene expression was reduced or disappeared in all cell lines examined (100%). In addition, we have attempted to classify all the cell lines into three groups according to the expression level; less than 10% (group I), 10-30% (group II) and approximately 50% (group III). We further investigated methylation status of the CpG sites in the exon 1 region of RUNX3 by methylation specific PCR (MSP), and studied the correlation between the expression level and hemizygous deletion as revealed by bicolor fluorescence in situ hybridization (FISH). The CpG sites were hypermethylated in 8 cell lines (53%) and the RUNX3 loci were hemizygously deleted in another 8 cell lines (53%). Furthermore group I, II, and III corresponded well to methylation-positive cell lines, cell lines showing hemizygous deletion, and the rest of cell lines without methylation or hemizygous deletion, respectively. These results suggest that a comprehensive study on RUNX3 using real-time RT-PCR, MSP, and FISH could be beneficial in understanding the pathogenetic mechanisms of human lung cancer at the molecular level. PMID:16142337

  19. Characterization of chromosome 1 abnormalities in malignant melanomas.

    PubMed

    Smedley, D; Sidhar, S; Birdsall, S; Bennett, D; Herlyn, M; Cooper, C; Shipley, J

    2000-05-01

    Chromosome 1 abnormalities are the most commonly detected aberrations in many cancers including malignant melanomas. Specific breakpoints are reported for malignant melanomas throughout the chromosome but especially at 1p36 and at several sites throughout 1p22-q21. In addition, partial deletions and loss of heterozygosity have been found on 1p indicating the possible location of tumor suppressor genes. Here we have characterized the involvement of chromosome 1 in a series of seven malignant melanoma cell lines. Initial chromosome painting studies revealed that six of the cell lines had chromosome 1 rearrangements. Deletions involving 1p10-32, 1q11-44, and 1q25-44 were observed. The other rearrangement breakpoints included three in the 1q10-p11 region with the rest at 1p36, 1p34, 1p32, 1p31, 1p12-13, 1q21, and 1q23. The breaks at 1q10-p11 were investigated further using an alpha-satellite 1 centromere probe and yeast artificial chromosomes (YACs) from the region. Two of the 1q10-p11 breaks mapped in the centromeric region, while the others mapped to variable sites. This suggests that the role of these rearrangements in the pathogenesis of melanomas does not involve the alteration of specific oncogenes in the breakpoint region. During the YAC mapping a previously undetected, small (<1 Mbp) del(1)(p10p11) was identified. This deletion lies within minimal overlapping deleted regions reported in head and neck as well as breast carcinomas and it could therefore facilitate the isolation of a carcinoma-associated tumor suppressor gene. PMID:10738310

  20. Sex chromosome system ZZ/ZW in Apareiodon hasemani Eigenmann, 1916 (Characiformes, Parodontidae) and a derived chromosomal region.

    PubMed

    Bellafronte, Elisangela; Schemberger, Michelle Orane; Artoni, Roberto Ferreira; Filho, Orlando Moreira; Vicari, Marcelo Ricardo

    2012-12-01

    Parodontidae fish show few morphological characteristics for the identification of their representatives and chromosomal analyses have provided reliable features for determining the interrelationships in this family. In this study, the chromosomes of Apareiodon hasemani from the São Francisco River basin, Brazil, were analyzed and showed a karyotype with 2n = 54 meta/submetacentric chromosomes, and a ZZ/ZW sex chromosome system. The study revealed active NORs located on pair 11 and additional 18S rDNA sites on pairs 7 and 22. The 5S rDNA locus was found in pair 14. It showed a pericentric inversion regarding the ancestral condition. The satellite DNA pPh2004 was absent in the chromosomes of A. hasemani, a shared condition with most members of Apareiodon. The WAp probe was able to detect the amplification region of the W chromosome, corroborating the common origin of the system within Parodontidae. These chromosomal data corroborate an origin for the ZW system of Parodontidae and aid in the understanding of the differentiation of sex chromosome systems in Neotropical fishes. PMID:23271937

  1. Identification of chromosome regions associated with seedling vigor in rice.

    PubMed

    Huang, Zheng; Yu, Ting; Su, Li; Yu, Si-Bin; Zhang, Zhi-Hong; Zhu, Ying-Guo

    2004-06-01

    Seedling vigor is important for optimum stand establishment in rice cropping. In this paper,a set of 264 F12 recombinant inbred lines (RILs) derived by single seed descent from a cross between Lemont (japonica) and Teqing (indica) was phenotyped for three seedling vigor related traits, including seed germination rate (GR), seedling shoot length and dry weight by the rolled paper towel tests. The phenotype data and a linkage map consisting of 198 DNA markers were combined to map quantitative trait loci (QTL) for seedling vigor by using a computer program QTLMapper1.0. A total of 13 putative main-effect QTL were detected. All of these QTL had much smaller effects on the traits with a mean R2 of 6.2%, ranging from 2.9% to 12.7%. As for digenic interaction, 18 pairs of epistatic loci with R2 > or = 5% were resolved with a mean R2 of 6.9% ,ranging from 5.1% to 11.8%, which was slightly larger than that of the main-effect QTL identified for the traits. The majority of the main-effect and epistatic loci detected for seedling vigor related traits were clustered in a few chromosome regions. Together, seven such chromosome regions (CRs), each with three or more seedling vigor main-effect and epistatic loci, were found to be highly associated with seedling vigor. These CRs can be classified into three types, i.e. M-CRs, E-CRs and ME-CRs. For some CRs just like CR(SV-6), the QTL within one CR were found to interact simultaneously with QTL within more than one other CRs to affect different seedling vigor related traits. The above results revealed that seedling vigor in rice is controlled by many loci, most of which have relatively small effects. Comparatively, epistasis as a genetic factor would be more important than main-effects of QTL for seedling vigor in rice. Nevertheless, the effects of the QTL are still large enough to be detected and in fact several chromosome regions were found to be highly associated with seedling vigor in very different populations as compared with

  2. A nuclease-hypersensitive region forms de novo after chromosome replication.

    PubMed

    Solomon, M J; Varshavsky, A

    1987-10-01

    Regular nucleosome arrays in eucaryotic chromosomes are punctuated at specific locations, such as active promoters and replication origins, by apparently nucleosome-free sites, also called nuclease-hypersensitive, or exposed, regions. The -400-base pair-exposed region within simian virus 40 (SV40) chromosomes is present in approximately 20% of the chromosomes in lytically infected cells and encompasses the replication origin, transcriptional enhancer, and both late and early SV40 promoters. We report that nearly all SV40 chromosomes lacked the exposed region during replication and that newly formed chromosomes acquired the exposed region of the same degree as did bulk SV40 chromosomes within 1 h after replication. Furthermore, a much lower but significant level of exposure was detectable in late SV40 replication intermediates, indicating that formation of the exposed region could start within minutes after passage of the replication fork. PMID:2824998

  3. Genome-wide semiquantitative microsatellite analysis of human hepatocellular carcinoma: discrete mapping of smallest region of overlap of recurrent chromosomal gains and losses.

    PubMed

    Nishimura, Takafumi; Nishida, Naoshi; Komeda, Toshiki; Fukuda, Yoshihiro; Ikai, Iwao; Yamaoka, Yoshio; Nakao, Kazuwa

    2006-05-01

    Recurrent chromosomal gains at 1q, 6p, 8q, and 17q, or losses at 1p, 4q, 6q, 8p, 9p, 13q, 16q, and 17p are common features of human hepatocellular carcinoma (HCC). For precise determination of the shortest region of overlap (SRO), 49 HCC obtained at the time of surgery or autopsy were subjected to comprehensive microsatellite analysis by using 400 markers distributed at almost equal distances throughout the 22 autosomes and X chromosomes. Each allele showing imbalance was subjected to comparative duplex polymerase chain reaction using a retained allele as an internal control to determine whether the imbalance was the result of chromosomal gain or loss. The following SRO of recurrent chromosomal gains and losses were determined: -1p36.22 approximately p36.33, D1S450-D1S2893, 5.0 mega-base pairs (Mbp); +1q23.3 approximately q25.3, D1S2878-D1S2619, 16.9 Mbp; -4q21.2 approximately q24, D4S2964-D4S1572, 23.0 Mbp; -6q23.3 approximately qter, D6S292-qter, 34.7 Mb; -8p22 approximately p23.1, D8S549-D8S550, 4.8 Mbp; +8q12.2 approximately q24.13, D8S260-D8S514, 61.8 Mbp; -13q13.3 approximately q22.1, D13S218-D13S156, 35.6 Mbp; -16q22.1 approximately qter, D16S503-qter, 26.7 Mbp; and -17p12 approximately pter, D17S921-pter, 14.2 Mbp. Contrary to our initial expectations, many HCC showed major deletions or additions of chromosome arms, so that a number of genes were included in the SRO. Although some putative oncogenes or tumor suppressor genes mapped in these SRO may be important, relative copy number changes of numerous other genes may affect pathogenesis of HCC. PMID:16682288

  4. [Comparative FISH analysis of C-positive regions of chromosomes of wood mice (Rodentia, Muridae, Sylvaemus)].

    PubMed

    Rubtsov, N B; Karamysheva, T V; Bogdanov, A S; Likhoshvaĭ, T V; Kartavtseva, I V

    2011-09-01

    The homology of DNA of C-positive centromeric regions of chromosomes in wood mice of the genus Sylvaemus (S. uralensis, S. fulvipectus, S. sylvaticus, S. flavicollis, and S. ponticus) was estimated for the first time. DNA probes were generated by microdissection from the centromeric regions of individual autosomes of each species, and their fluorescence in situ hybridization (FISH) with metaphase chromosomes of representatives of all studied wood mouse species was carried out. Unlike in the chromosomal forms and races of S. uralensis, changes in the DNA composition of the chromosomal centromeric regions in the wood mouse species of the genus Sylvaemus (including closely related S. flavicollis and S. ponticus) are both quantitative and qualitative. The patterns of FISH signals after in situ hybridization of the microdissection DNA probes with chromosomes of the species involved in the study demonstrate significant differences between C-positive regions of wood mouse chromosomes in the copy number and the level of homology of repetitive sequences as well as in the localization of homologous repetitive sequences. It was shown that C-positive regions of wood mouse chromosomes can contain both homologous and distinct sets of repetitive sequences. Regions enriched with homologous repeats were detected either directly in C-positive regions of individual chromosomes or only on the short arms of acrocentrics, or at the boundary of C-positive and C-negative regions. PMID:22117409

  5. Topological Organization of Multi-chromosomal Regions by Firre

    PubMed Central

    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. Regions of the polytene chromosomes of Drosophila virilis carrying multiple dispersed p Dv 111 DNA sequences

    SciTech Connect

    Gubenko, I.S.; Evgen'ev, M.B.

    1986-09-01

    The cloned sequences of p Dv 111 DNA hybridized in situ with more than 170 regions of Drosophila virilis salivary gland chromosomes. Comparative autoradiography of in situ hybridization and the nature of pulse /sup 3/H-thymidine and /sup 3/H-deoxycytidine incorporation into the polytene chromosomes of D. virilis at the puparium formation stage showed that the hybridization sites of p Dv 111 are distributed not only in the heterochromatic regions but also in the euchromatic regions of the chromosomes that are not late replicating. Two distinct bands of hybridization of p Dv 111 /sup 3/H-DNA were observed in the region of the heat shock puff 20CD. The regions of the distal end of chromosome 2, in which breaks appeared during radiation-induced chromosomal rearrangements, hybridized with the p Dv 111 DNA.

  7. [The role of chromosomal regions anchored to the nuclear envelope in the functional organization of chromosomes].

    PubMed

    Shabarina, A N; Shostak, N G; Glazkov, M V

    2010-09-01

    The functional characteristics of the DNA fragments responsible for chromosome attachment to the nuclear envelope during the interphase (neDNAs) have been studied. The neDNAs flanking the transgene have been found to promote a steadily high rate of its expression, irrespective of the site of its insertion into the host chromosomes. At the same time, neDNAs themselves have no transcription regulatory functions. PMID:21061611

  8. Isolation and refined regional mapping of expressed sequences from human chromosome 21

    SciTech Connect

    Kao, F.T.; Yu, J.; Patterson, D.

    1994-10-01

    To increase candidate genes from human chromosome 21 for the analysis of Down syndrome and other genetic diseases localized on this chromosome, we have isolated and studied 9 cDNA clones encoded by chromosome 21. For isolating cDNAs, single-copy microclones from a chromosome 21 microdissection library were used in direct screening of various cDNA libraries. Seven of the cDNA clones have been regionally mapped on chromosome 21 using a comprehensive hybrid mapping panel comprising 24 cell hybrids that divide the chromosome into 33 subregions. These cDNA clones with refined mapping positions should be useful for identification and cloning of genes responsible for the specific component phenotypes of Down syndrome and other diseases on chromosome 21, including progressive myoclonus epilepsy in 21q22.3. 12 refs., 2 figs., 1 tab.

  9. Cosmid clones derived from both euchromatic and heterochromatic regions of the human Y chromosome.

    PubMed Central

    Wolfe, J; Erickson, R P; Rigby, P W; Goodfellow, P N

    1984-01-01

    Clones containing sequences derived from the human Y chromosome have been isolated from cosmid libraries of a human-mouse hybrid cell line. These libraries were constructed in the new expression vectors Homer V and Homer VI. The collection of cosmids isolated is enriched for unique sequence DNA and only a few of the cosmids contain the tandemly repeated sequences which constitute a major portion of the Y chromosome. Three cosmids have been studied in detail. One cosmid shows extensive homology over at least 20 kb with the long arm of the X chromosome; this homology is outside the predicted homology region required for sex chromosome pairing. The other two clones contain unique sequences specific to the Y chromosome and both map to the heterochromatic region of the Y chromosome long arm. Images Fig. 1. Fig. 2. PMID:6092051

  10. Genetic and Molecular Mapping of Chromosome Region 85a in Drosophila Melanogaster

    PubMed Central

    Jones, W. K.; Rawls-Jr., J. M.

    1988-01-01

    Chromosome region 85A contains at least 12 genetic complementation groups, including the genes dhod, pink and hunchback. In order to better understand the organization of this chromosomal segment and to permit molecular studies of these genes, we have carried out a genetic analysis coupled with a chromosome walk to isolate the DNA containing these genes. Complementation tests with chromosomal deficiencies permitted unambiguous ordering of most of the complementation groups identified within the 85A region. Recombinant bacteriophage clones were isolated that collectively span over 120 kb of 85A DNA and these were used to produce a molecular map of the region. The breakpoint sites of a number of 85A chromosome rearrangements were localized on the molecular map, thereby delimiting regions of the DNA that contain the various genetic complementation groups. PMID:2852138

  11. Construction of a chromosome specific library of human MARs and mapping of matrix attachment regions on human chromosome 19.

    PubMed Central

    Nikolaev, L G; Tsevegiyn, T; Akopov, S B; Ashworth, L K; Sverdlov, E D

    1996-01-01

    Using a novel procedure a representative human chromosome 19-specific library was constructed of short sequences, which bind preferentially to the nuclear matrix (matrix attachment regions, or MARs). Judging by 20 clones sequenced so far, the library contains > 50% of human inserts, about 90% of which are matrix-binding by the in vitro test. Computer analysis of sequences of eight human MARs did not reveal any significant homologies with the EMBL Nucleotide Data Base entries as well as between MARs themselves. Eight MARs were assigned to individual positions on the chromosome 19 physical map. The library constructed can serve as a good source of MAR sequences for comparative analysis and classification and for further chromosome mapping of MARs as well. PMID:8614638

  12. Genetic Divergence in Domesticated and Non-Domesticated Gene Regions of Barley Chromosomes

    PubMed Central

    Yan, Songxian; Sun, Dongfa; Sun, Genlou

    2015-01-01

    Little is known about the genetic divergence in the chromosomal regions with domesticated and non-domesticated genes. The objective of our study is to examine the effect of natural selection on shaping genetic diversity of chromosome region with domesticated and non-domesticated genes in barley using 110 SSR markers. Comparison of the genetic diversity loss between wild and cultivated barley for each chromosome showed that chromosome 5H had the highest divergence of 35.29%, followed by 3H, 7H, 4H, 2H, 6H. Diversity ratio was calculated as (diversity of wild type – diversity of cultivated type)/diversity of wild type×100%. It was found that diversity ratios of the domesticated regions on 5H, 1H and 7H were higher than those of non-domesticated regions. Diversity ratio of the domesticated region on 2H and 4H is similar to that of non-domesticated region. However, diversity ratio of the domesticated region on 3H is lower than that of non-domesticated region. Averaged diversity among six chromosomes in domesticated region was 33.73% difference between wild and cultivated barley, and was 27.56% difference in the non-domesticated region. The outcome of this study advances our understanding of the evolution of crop chromosomes. PMID:25812037

  13. DNA repair and crossing over favor similar chromosome regions as discovered in radiation hybrid of Triticum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The uneven distribution of recombination across the length of chromosomes results in inaccurate estimates of genetic to physical distances. In wheat (Triticum aestivum L.) chromosome 3B, it has been estimated that 90% of the cross over occurs in distal sub-telomeric regions representing 40% of the...

  14. Regional localization of the gene for thyroid peroxidase to human chromosome 2p25 and mouse chromosome 12C

    SciTech Connect

    Endo, Yuichi; Onogi, Satoshi; Fujita, Teizo

    1995-02-10

    Thyroid peroxidase (TPO) plays a central role in thyroid gland function. The enzyme catalyzes two important reactions of thyroid hormone synthesis, i.e., the iodination of tyrosine residues in thyroglobulin and phenoxy-ester formation between pairs of iodinated tyrosines to generate the thyroid hormones, thyroxine and triiodothyronine. Previously, we isolated the cDNAs encoding human and mouse TPOs and assigned the human TPO gene to the short arm of chromosome 2 by somatic cell hybrid mapping. By a similar analysis of DNA from somatic cell hybrids, the human TPO gene was mapped to 2pter-p12. The mouse TPO gene was localized to chromosome 12 using a rat TPO cDNA as a probe to hybridize with mouse-hamster somatic cell hybrids. In this study, we used fluorescence in situ hybridization (FISH) to confirm the localization of human and mouse TPO genes to human chromosome 2 and mouse chromosome 12 and to assign them regionally to 2p25 and 12C, respectively. 7 refs., 1 fig.

  15. The subtelomeric region of the Arabidopsis thaliana chromosome IIIR contains potential genes and duplicated fragments from other chromosomes.

    PubMed

    Wang, Chi-Ting; Ho, Chia-Hsing; Hseu, Ming-Jhy; Chen, Chung-Mong

    2010-09-01

    The subtelomere and a portion of the associated telomeric region (together named 3RTAS) of chromosome IIIR from the Arabidopsis thaliana ecotypes Columbia (Col) and Wassilewskija (Ws) were specifically amplified by polymerase chain reaction and subsequently cloned and sequenced. The centromere-proximal portion of 3RTAS from both ecotypes contained two newly identified potential genes, one encoding the chloroplast luminal 19-kDa protein precursor and the other encoding three potential alternatively spliced CCCH-type zinc finger proteins. The telomere-proximal portion of 3RTAS from the Col ecotype contained short duplicated fragments derived from chromosomes I, II, and III, and that from the Ws ecotype contained a duplicated fragment derived from chromosome V. Each duplicated fragment has diverged somewhat in sequence from that of the ectopic template. Small patches of homologous nucleotides were found within the flanking sequences of both the duplicated fragments and the corresponding ectopic template sequences. The structural characteristics of these duplicated fragments suggest that they are filler DNAs captured by non-homologous end joining during double-strand break repair. Our characterization of 3RTAS not only filled up a gap in the chromosome IIIR sequence of A. thaliana but also identified new genes with unknown functions. PMID:20652368

  16. Detailed comparative mapping of cereal chromosome regions corresponding to the Ph1 locus in wheat

    SciTech Connect

    Foote, T.; Roberts, M.; Kurata, N.

    1997-10-01

    Detailed physical mapping of markers from rich chromosome 9, and from syntenous (at the genetic level) regions of other cereal genomes, has resulted in rice yeast artificial chromosome (YAC) contigs spanning parts of rice 9. This physical mapping, together with comparative genetic mapping, has demonstrated that synteny has been largely maintained between the genomes of several cereals at the level of contiged YACs. Markers located in one region of rice chromosome 9 encompassed by the YAC contigs have exhibited restriction fragment length polymorphism (RFLP) using deletion lines for the Ph1 locus. This has allowed demarcation of the region of rice chromosome 9 syntenous with the phlb and phlc deletions in wheat chromosome 5B. A group of probes located in wheat homoeologous group 5 and barley chromosome 5H, however, have synteny with rice chromosomes other than 9. This suggests that the usefulness of comparative trait analysis and of the rice genome as a tool to facilitate gene isolation will differ from one region to the next, and implies that the rice genome is more ancestral in structure than those of the Triticeae. 38 refs., 2 figs., 1 tab.

  17. Detailed Comparative Mapping of Cereal Chromosome Regions Corresponding to the Ph1 Locus in Wheat

    PubMed Central

    Foote, T.; Roberts, M.; Kurata, N.; Sasaki, T.; Moore, G.

    1997-01-01

    Detailed physical mapping of markers from rice chromosome 9, and from syntenous (at the genetic level) regions of other cereal genomes, has resulted in rice yeast artificial chromosome (YAC) contigs spanning parts of rice 9. This physical mapping, together with comparative genetic mapping, has demonstrated that synteny has been largely maintained between the genomes of several cereals at the level of contiged YACs. Markers located in one region of rice chromosome 9 encompassed by the YAC contigs have exhibited restriction fragment length polymorphism (RFLP) using deletion lines for the Ph1 locus. This has allowed demarcation of the region of rice chromosome 9 syntenous with the ph1b and ph1c deletions in wheat chromosome 5B. A group of probes located in wheat homoeologous group 5 and barley chromosome 5H, however, have synteny with rice chromosomes other than 9. This suggests that the usefulness of comparative trait analysis and of the rice genome as a tool to facilitate gene isolation will differ from one region to the next, and implies that the rice genome is more ancestral in structure than those of the Triticeae. PMID:9335614

  18. High-resolution G-banding and nucleolus-organizer regions of chromosomes of vole Microtus kirgisorum

    SciTech Connect

    Mazurok, N.A.; Rubtsov, N.B.; Ovechkina, Y.Y.

    1995-08-01

    The use of G-banding of chromosomes in combination with the pipette method of chromosome preparation at the early metaphase made it possible to distinguish about 520 segments in the haploid chromosome set of vole Microtus kirgisorum. The idiogram of M. kirgisorum chromosomes was obtained on the basis of detailed investigation of chromosomes at different condensation levels. Data of the localization and the number of nucleolus-organizer regions are given. 16 refs., 3 figs.

  19. [Nucleolus organizer regions and B-chromosomes of field mice (Mammalia, Rodentia, Apodemus)].

    PubMed

    Boeskorov, G G; Kartavtseva, I V; Zagorodniuk, I V; Belianin, A N; Liapunova, E A

    1995-02-01

    Distribution of nucleolus organizer regions (NORs) in karyotypes was studied in 10 species of wood mice, including Apodemus flavicollis, A. sylvaticus, A. uralensis (= A. microps), A. fulvipectus (= A. falzfeini), A. ponticus, A. hyrcanicus, A. mystacinus, A. agrarius, A. peninsulae, and A. speciosus. Peculiarities of NOR location in karyotypes can be used in interspecific diagnostics of wood mice. Intraspecific polymorphism of A. sylvaticus, A. agrarius, and A. peninsulae in terms of the number of NORs and their localization in chromosomes can serve as evidence for karyological differentiation in certain populations of these species. The minimum number of active NORs in mice of the genus Apodemus is two to four. Two A. flavicollis wood mice with karyotypes containing one small acrocentric B-chromosome (2n = 49) were identified among animals captured in Estonia. In A. peninsulae, B-chromosomes were found among animals captured in the following regions: the vicinity of Kyzyl (one mouse with 17 microchromosomes, 2n = 65); the vicinity of Birakan (two mice with one metacentric chromosome each, 2n = 49); and in the Ussuri Nature Reserve (one mouse with five B-chromosomes, including three metacentric and two dotlike chromosomes; 2n = 65). In the latter animal, the presence of NORs on two metacentric B-chromosomes was revealed; this is the first case of identification of active NORs on extra chromosomes of mammals. PMID:7721059

  20. Nucleolus organizer regions and B-chromosomes of wood mice (mammalia, rodentia, Apodemus)

    SciTech Connect

    Boeskorov, G.G.; Kartavtseva, I.V.; Zagorodnyuk, I.V.; Belyanin, A.N.; Lyapunova, E.A.

    1995-02-01

    Distribution of nucleolus organizer regions (NORs) in karyotypes was studied in 10 species of wood mice, including Apodemus flavicollis, A. sylvaticus, A. uralensis (=A. microps), A. fulvipectus (=A. falzfeini), A. ponticus, A. hyrcanicus, A. mystacinus, A. agrarius, A. peninsulae, and A. speciosus. Peculiarities of NOR location in karyotypes can be used in interspecific diagnostics of wood mice. Intraspecific polymorphism of A. sylvaticus, A. agrarius, and A. peninsulae in terms of the number of NORs and their localization in chromosomes can serve as evidence for karyological differentiation in certain populations of these species. The minimum number of active NORs in mice of the genus Apodemus is two to four. Two A. flavicollis wood mice with karyotypes containing one small acrocentric B-chromosome (2n = 49) were identified among animals captured in Estonia. In A. peninsulae, B-chromosomes were found among animals captured in the following regions: the vicinity of Kyzyl (one mouse with 17 microchromosomes, 2n = 65); the vicinity of Birakan (two mice with one metacentric chromosome each, 2n = 49); and in the Ussuri Nature Reserve (one mouse with five B-chromosomes, including three metacentric and two dotlike chromosomes; 2n = 53). In the latter animal, the presence of NORs on two metacentric B-chromosomes was revealed; this is the first case of identification of active NORs on extra chromosomes of mammals. 29 refs., 4 figs., 1 tab.

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

    SciTech Connect

    Kumar, Shrawan; Kimberling, W.J.; Pinnt, J.

    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. A 37-kb fragment common to the pericentromeric region of human chromosomes 13 and 21 and to the ancestral inactive centromere of chromosome 2

    SciTech Connect

    Charlieu, J.P.; Laurent, A.M.; Orti, R.; Bellis, M.; Roizes, G. INSERM U 249, Montpellier ); Viegas-Pequignot, E. )

    1993-03-01

    A YAC clone from a chromosome 21-specific partial library was localized by in situ hybridization to the pericentromeric region of chromosomes 13 and 21 and to the long arm of chromosome 2, where an ancestral inactive centromere is present. Restriction mapping of the insert showed that it may contain tandemly repeated DNA. Probes for [alpha]-satellite and satellite II and III failed to hybridize with the cloned DNA. Shotgun subcloning might reveal a sequence that seems to be specific for chromosome 21. Alu-PCR was performed to generate probes from the YAC clone to map it more precisely, using a somatic hybrid containing only human chromosome 21. The inter-Alu sequences thus isolated were found to be clustered in an approximately 37-kb-long fragment common to chromosomes 2, 13, and 21, which might be involved in the centromeric function of these chromosomes. 33 refs., 7 figs.

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

    SciTech Connect

    Dinulos, M.B.; Disteche, C.M.; Bassi, M.T.

    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.

  4. Isolation, characterization, and regional mapping of microclones from a human chromosome 21 microdissection library

    SciTech Connect

    Yu, J.; Hartz, J.; Yisheng Xu; Gemmill, R.M.; Patterson, D.; Kao, Faten ); Gemmill, R.M.; Patterson, D.; Kao, Fa-Ten ); Korenberg, J.R. )

    1992-08-01

    Thirty-four unique-sequence microclones were isolated from a previously described microdissection library of human chromosome 21 and were regionally mapped using a cell hybrid mapping panel which consists of six cell hybrids and divides chromosome 21 into eight regions. The mapping results showed that the microclones were unevenly distributed along chromosome 21, with the majority of microclones located in the distal half portion of the long arm, between 21q21.3 and 21qter. The number of unique-sequence clones began to decrease significantly from 21q21.2 to centromere and extending to the short arm. This finding is consistent with those reported in other chromosome 21 libraries. Thus, it may be inferred that the proximal portion of the long arm of chromosome 21 contains higher proportions of repetitive sequences, rather than unique sequences of genes. The microclones were also characterized for insert size and were used to identify the corresponding genomic fragments generated by HindIII. In addition, the authors demonstrated that the microclones with short inserts can be efficiently used to identify YAC (yeast artificial chromosome) clones with large inserts, for increased genomic coverage for high-resolution physical mapping. They also used 200 unique-sequence microclones to screen a human liver cDNA library and identified two cDNA clones which were regionally assigned to the 21q21.3-q22.1 region. Thus, generation of unique-sequence microclones from chromosome 21 appears to be useful to isolate and regionally map many cDNA clones, among which will be candidate genes for important diseases on chromosome 21, including Down syndrome, Alzheimer disease, amyotrophic lateral sclerosis, and one form of epilepsy.

  5. 3. 6-Mb genomic and YAC physical map of the Down syndrome chromosome region on chromosome 21

    SciTech Connect

    Dufresne-Zacharia, M.C.; Dahmane, N.; Theophile, D.; Orti, R.; Chettouh, Z.; Sinet, P.M.; Delabar, J.M. )

    1994-02-01

    The Down syndrome chromosome region (DCR) on chromosome 21 has been shown to contain a gene(s) important in the pathogenesis of Down syndrome. The authors constructed a long-range restriction map of the D21S55-D21S65 region covering the proximal part of the DCR. Pulsed-field gel electrophoresis of lymphocyte DNA digested with three rare cutting enzymes, NotI, NruI, and Mlu1, was used to establish two physical linkage groups of 5 and 7 markers, respectively, spanning 4.6 Mb on the NotI map. Mapping analysis of 40 YACs allowed the selection of 13 YACs covering 95% of the D21S55-D21S65 region and spanning 3.6 Mb. The restriction maps of these YACs and their positioning on the genomic map allowed 19 markers to be ordered, including 4 NotI linking clones, 9 polymorphic markers, the CBR gene, and the AML1 gene. The distances between markers could also be estimated. This physical map and the location of eight NotI sites between D21S55 and D21S17 should facilitate the isolation of previously unidentified genes in this region. 34 refs., 2 figs., 2 tabs.

  6. The mouse and human excitatory amino acid transporter gene (EAAT1) maps to mouse chromosome 15 and a region of syntenic homology on human chromosome 5

    SciTech Connect

    Kirschner, M.A.; Arriza, J.L.; Amara, S.G.

    1994-08-01

    The gene for human excitatory amino acid transporter (EAAT1) was localized to the distal region of human chromosome 5p13 by in situ hybridization of metaphase chromosome spreads. Interspecific backcross analysis identified the mouse Eaat1 locus in a region of 5p13 homology on mouse chromosome 15. Markers that are linked with EAAT1 on both human and mouse chromosomes include the receptors for leukemia inhibitory factor, interleukin-7, and prolactin. The Eaat1 locus appears not be linked to the epilepsy mutant stg locus, which is also on chromosome 15. The EAAT1 locus is located in a region of 5p deletions that have been associated with mental retardation and microcephaly. 22 refs., 2 figs.

  7. DNA methylation and heterochromatinization in the male-specific region of the primitive Y chromosome of papaya

    PubMed Central

    Zhang, Wenli; Wang, Xiue; Yu, Qingyi; Ming, Ray; Jiang, Jiming

    2008-01-01

    Sex chromosomes evolved from autosomes. Recombination suppression in the sex-determining region and accumulation of deleterious mutations lead to degeneration of the Y chromosomes in many species with heteromorphic X/Y chromosomes. However, how the recombination suppressed domain expands from the sex-determining locus to the entire Y chromosome remains elusive. The Y chromosome of papaya (Carica papaya) diverged from the X chromosome approximately 2–3 million years ago and represents one of the most recently emerged Y chromosomes. Here, we report that the male-specific region of the Y chromosome (MSY) spans ∼13% of the papaya Y chromosome. Interestingly, the centromere of the Y chromosome is embedded in the MSY. The centromeric domain within the MSY has accumulated significantly more DNA than the corresponding X chromosomal domain, which leads to abnormal chromosome pairing. We observed four knob-like heterochromatin structures specific to the MSY. Fluorescence in situ hybridization and immunofluorescence assay revealed that the DNA sequences associated with the heterochromatic knobs are highly divergent and heavily methylated compared with the sequences in the corresponding X chromosomal domains. These results suggest that DNA methylation and heterochromatinization play an important role in the early stage of sex chromosome evolution. PMID:18593814

  8. Erratum: Letter to the Editor: Exclusion of primary congenital glaucoma (buphthalmos) from two candidate regions of chromosome arm 6p and chromosome 11

    SciTech Connect

    1996-03-01

    This {open_quotes}Letter to the Editor{close_quotes} is the reprint of a corrected table from a previous paper about the exclusion of primary congenital glaucoma from two candidate regions of chromosome arm 6p and chromosome 11.

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

    PubMed Central

    2012-01-01

    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. PMID:23194088

  10. Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two additional regions identified.

    PubMed Central

    Cropp, C S; Lidereau, R; Campbell, G; Champene, M H; Callahan, R

    1990-01-01

    The loss of heterozygosity (LOH) at specific regions of the human genome in tumor DNA is recognized as evidence for a tumor-suppressor gene located within the corresponding region of the homologous chromosome. Restriction fragment length polymorphism analysis of a panel of primary human breast tumor DNAs has led to the identification of two additional regions on chromosomes 17q and 18q that frequently are affected by LOH. Deletions of each of these regions have a significant correlation with clinical parameters that are associated with aggressive breast carcinomas. Previous restriction fragment length polymorphism analysis of this panel of tumors has uncovered several other frequently occurring mutations. LOH on chromosome 18q frequently occurs in tumors with concomitant LOH of loci on chromosomes 17p and 11p. Similarly, tumors having LOH on 17q also have LOH on chromosomes 1p and 3p. This suggests that certain combinations of mutations may collaborate in the development and malignant progression of breast carcinomas. Images PMID:1977164

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

    SciTech Connect

    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.

  12. Gonadoblastoma: Molecular definition of the susceptibility region on the Y chromosome and role of TSPY

    SciTech Connect

    Tsuchiya, K.; Sultana, R.; Donlan, M.

    1994-09-01

    Gonadoblastomas are gonadal neoplasms that arise almost exclusively in the dysgenetic gonads of 46,XY sex-reversed females. The frequency of gonadoblastoma in patients who have dysgenetic gonads and a Y chromosome is at least 30%. In contrast 45,X Turner females who also have dysgenetic gonads do not develop this tumor. The high frequency of gonadoblastoma in sex-reversed females compared to Turner females has led to the hypothesis that there is a gene on the Y chromosome that is involved in the development of the tumor. This gene has been called the gonadoblastoma locus on the Y chromosome, or GBY. Deletion mapping of sex-reversed females with gonadoblastoma and partial Y chromosomes has previously localized the GBY gene to a region near the centromere. Using sequence-tagged sites, we have further sublocalized GBY in a patient with gonadoblastoma and a minute Y-derived marker chromosome. This region includes parts of intervals 3 and 4 of the Y chromosome. Based on the overlapping YAC contig map of the Y chromosome, this critical region is approximately 3 Mb. Using sex-reversed females with different deletions of Yp we have also localized the testis-specific protein, Y-encoded (TSPY) gene to interval 3D, which is within the gonadoblastoma critical region. TSPY consists of a repetitive gene family that is part of the DYZ5 locus. Expression of this gene has previously been shown to be limited to the testis. We have found expression of TSPY by RT-PCR in gonadoblastomas from two different individuals. In one of these patients, expression was observed in a unilateral gonadoblastoma, but not in the contralateral streak gonad. These findings suggest that TSPY may play a role in the development of gonadoblastomas.

  13. Localization of the tight junction protein gene TJP1 to human chromosome 15q13, distal to the Prader-Willi/Angelman region, and to mouse chromosome 7

    SciTech Connect

    Mohandas, T.K.; Chen, X.N.; Korenberg, J.R.

    1995-12-10

    The gene encoding the tight junction (zonula occludens) protein, TJP1, was mapped to human chromosome 15q13 by fluorescence in situ hybridization (FISH) using a cDNA probe. The Jackson Laboratory backcross DNA panel derived from the cross (C57BL/6JEi X SPRET/Ei) F1 females X SPRET/Ei males was used to map the mouse Tjp1 to chromosome 7 near position 30 on the Chromosome Committee Map, a region with conserved homology to human chromosome 15q13. FISH studies on metaphases from patients with the Prader-Willi (PWS) or the Angelman syndrome (AS) showed that TJP1 maps close but distal to the PWS/AS chromosome region. 13 refs., 2 figs.

  14. Organization of the und R chromosome region in maize

    SciTech Connect

    Kermicle, J.

    1989-07-01

    Maize is highly polymorphic in pattern of anthocyanin pigmentation. That portion of the total variation which is attributable to one gene is revealed when alleles from various sources are incorporated into a standard line by backcrossing before comparison under uniform environments. The variation associated with such collections of {und R} alleles is discontinuous, suggesting the presence of discrete units of function. Alleles comprising more than one such element constitute an allelic complex or gene family. An objective of the early years of investigation under this grant was to work out the arrangement of genic elements in such allelic complexes. Elements in a complex are identified by independent mutation and separability by recombination, the latter serving also to order them in the chromosome. Alleles having from one to three elements each were represented among five accessions of the colored-seed, colored-plant class ({und R-r}). Nine different genic elements were identified. This line of inquiry has been de-emphasized in recent years in deference to investigating the organization of individual genic elements. We have focused on a set of readily distinguished elements that were identified or produced in the analysis of allelic complexes. 7 refs., 1 tab.

  15. A yeast artificial chromosome contig of the critical region for cri-du-chat syndrome

    SciTech Connect

    Goodart, S.A.; Rojas, K.; Overhauser, J.

    1994-11-01

    Cri-du-chat is a chromosomal deletion syndrome characterized by partial deletion of the short arm of chromosome 5. The clinical symptoms include growth and mental retardation, microcephaly, hypertelorism, epicanthal folds, hyptonia, and a high-pitched monochromatic cry that is usually considered diagnostic for the syndrome. Recently, a correlation between clinical features and the extent of the chromosome 5 deletions has identified two regions of the short arm that appear to be critical for the abnormal development manifested in this syndrome. Loss of a small region in 5p15.2 correlates with all of the clinical features of cri-du-chat with the exception of the cat-like cry, which maps to 5p15.3. Here the authors report the construction of a YAC contig that spans the chromosomal region in 5p15.2 that plays a major role in the etiology of the cri-du-chat syndrome. YACs that span the 2-Mb cri-du-chat critical region have been identified and characterized. This YAC contig lays the groundwork for the construction of a transcriptional map of this region and the eventual identification of genes involved in the clinical features associated with the cri-du-chat syndrome. It also provides a new diagnostic tool for cri-du-chat in the shape of a YAC clone that may span the entire critical region. 24 refs., 4 figs., 2 tabs.

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

    PubMed Central

    Bisognin, Andrea; Bortoluzzi, Stefania; Danieli, Gian Antonio

    2004-01-01

    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. PMID:15176974

  17. Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17

    SciTech Connect

    Cheng, S.V.; Nadeau, J.H.; Tanzi, R.E.; Watkins, P.C.; Jagadesh, J.; Taylor, B.A.; Haines, J.L.; Sacchi, N.; Gusella, J.F. )

    1988-08-01

    Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid {beta} precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, the authors have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS.

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

    PubMed

    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. PMID:23494254

  19. Characterization of a panel of somatic cell hybrids for regional mapping of the mouse X chromosome

    SciTech Connect

    Avner, P.; Arnaud, D.; Amar, L.; Cambrou, J.; Winking, H.; Russell, L.B.

    1987-08-01

    A panel of five hybrid cell lines containing mouse X chromosomes with various deletions has been obtained by fusing splenocytes from male mice carrying one of a series of reciprocal X-autosome translocations with the azaguanine-resistant Chinese hamster cell line CH3g. These hybrids have been extensively characterized by using the allozymes hypoxanthine/guanine phosphoribosyltransferase (encoded by the Hprt locus) and ..cap alpha..-galactosidase (Ags) and a series of 11 X-chromosome-specific DNA probes whose localization had been previously established by linkage studies. Such studies have established the genetic breakpoints of the T(X;12)13R1 and T(X;2)14R1 X-autosome translocations on the X chromosome and provided additional information as to the X-chromosome genetic breakpoints of the T(X;16)16H, T(X;4)7R1, and T(X;7)6R1 translocations. The data establish clearly that both the T(X;7)5RI and T(X;12)13R1 X-chromosome breakpoints are proximal to Hprt, the breakpoint of the former being more centromeric, lying as it does in the 9-centimorgan interval between the ornithine transcarbamoylase (Otc) and DXPas7 (M2C) loci. These five hybrid cell lines provide, with the previously characterized EBS4 hybrid cell line, a nested series of seven mapping intervals distributed along the length of the mouse X chromosome. Their characterization not only allows further correlation of the genetic and cytological X-chromosome maps but also should permit the rapid identification of DNA probes specific for particular regions of the mouse X chromosome.

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

    PubMed

    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. PMID:24247273

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

    PubMed Central

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

    2014-01-01

    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. PMID:24247273

  2. A radiation hybrid map of the BRCA1 region of chromosome 17q12-q21

    SciTech Connect

    Abel, K.J.; Boehnke, M.; Prahalad, M.; Flejter, W.L.; Watkins, M.; Chandrasekharappa, S.C.; Glover, T.W. Howard Hughes Medical Institute, Ann Arbor, MI ); Ho, P.; VanderStoep, J.; Weber, B.L. ); Collins, F.S. Michigan Human Genome Center, Ann Arbor, MI Howard Hughes Medical Institute, Ann Arbor, MI )

    1993-09-01

    The chromosomal region 17q12-q21 contains a gene (BRCA1) conferring susceptibility to early-onset familial breast and ovarian cancer. An 8000-rad radiation-reduced hybrid (RH) panel was constructed to provide a resource for long-range mapping of this region. A large fraction of the hybrids ([approximately]90%) retained detectable human chromosome 17 sequences. The complete panel of 76 hybrids was scored for the presence or absence of 22 markers from this chromosomal region, including 14 cloned genes, seven microsatellite repeats, and one anonymous DNA segment. Statistical analysis of the marker retention data employing multipoint methods provided both comprehensive and framework maps of this chromosomal region, including distance estimates between adjacent markers. The comprehensive RH map includes 17 loci and spans 179 cRays[sub (8000)]. Likelihood ratios of at least 1000:1 support the 10-locus framework order: cen-D17S250-ERBB2-(THRA1, TOP2A)-D17S855-PPY-D17S190-MTBT1-GP3A-BTR-D17S588-tel. The order obtained from RH mapping, when used in conjunction with other methods, will be useful in linkage analysis of breast cancer families and will facilitate the development of a physical map of this region. 42 refs., 3 figs., 2 tabs.

  3. Structural analysis and physical mapping of a pericentromeric region of chromosome 5 of Arabidopsis thaliana.

    PubMed

    Tutois, S; Cloix, C; Cuvillier, C; Espagnol, M C; Lafleuriel, J; Picard, G; Tourmente, S

    1999-01-01

    The Arabidopsis thaliana CIC YAC 2D2, 510 kb long and containing a small block of 180 bp satellite units was subcloned after EcoR1 digestion in the pBluescript plasmid. One of these clones was mapped genetically in the pericentromeric region of chromosome 5. The analysis of 40 subclones of this YAC showed that they all contain repeated sequences with a high proportion of transposable elements. Three new retrotransposons, two Ty-3 Gypsy-like and one Ty-1 Copia, were identified in addition to two new tandem-repeat families. A physical map of the chromosome 5 pericentromeric region was established using CIC YAC clones, spanning around 1000 kb. This contig extends from the CIC YAC 9F5 and 7A2 positioned on the left arm of chromosome 5 to a 5S rDNA genes block localized by in-situ hybridization in the pericentromeric region. Hybridization of the subclones on the CIC YAC library showed that some of them are restricted to the pericentromeric region of chromosome 5 and represent specific markers of this region. PMID:10328626

  4. Exclusion of primary congenital glaucoma (buphthalmos) from two candidate regions of chromosome arm 6p and chromosome 11

    SciTech Connect

    Akarsu, A.N.; Hossain, A.; Sarfarazi, M.

    1996-01-22

    Primary congenital glaucoma (gene symbol: GLC3) is characterized by an improper development of the aqueous outflow system. The reduced outflow of fluid results in an increased intraocular pressure leading to buphthalmos, optic nerve damage, and eventual visual impairment. GLC3 is a heterogeneous condition with an estimated incidence of 1:2,500 in Middle Eastern and 1:10,000 in Western countries. In many families, GLC3 is an autosomal recessive trait with presentation of an earlier age-of-onset, high intraocular pressure, enlarged cloudy cornea, buphthalmos, and a more aggressive course. The pathogenesis of GLC3 remains elusive despite extensive histologic efforts to identify a single anatomic defect. Recent advances in positional mapping and cloning of human disorders provided an opportunity to identify chromosome locations of the GLC3 phenotype. Our laboratory is currently involved in the mapping of this condition by using a combination of candidate chromosome regions associated with the GLC3 phenotype and by a general positional mapping strategy. 16 refs., 3 tabs.

  5. Asymmetric Distribution of Gene Expression in the Centromeric Region of Rice Chromosome 5

    PubMed Central

    Mizuno, Hiroshi; Kawahara, Yoshihiro; Wu, Jianzhong; Katayose, Yuichi; Kanamori, Hiroyuki; Ikawa, Hiroshi; Itoh, Takeshi; Sasaki, Takuji; Matsumoto, Takashi

    2011-01-01

    There is controversy as to whether gene expression is silenced in the functional centromere. The complete genomic sequences of the centromeric regions in higher eukaryotes have not been fully elucidated, because the presence of highly repetitive sequences complicates many aspects of genomic sequencing. We performed resequencing, assembly, and sequence finishing of two P1-derived artificial chromosome clones in the centromeric region of rice (Oryza sativa L.) chromosome 5 (Cen5). The pericentromeric region, where meiotic recombination is silenced, is located at the center of chromosome 5 and is 2.14 Mb long; a total of six restriction-fragment-length polymorphism markers (R448, C1388, S20487S, E3103S, C53260S, and R2059) genetically mapped at 54.6 cM were located in this region. In the pericentromeric region, 28 genes were annotated on the short arm and 45 genes on the long arm. To quantify all transcripts in this region, we performed massive parallel sequencing of mRNA. Transcriptional density (total length of transcribed region/length of the genomic region) and expression level (number of uniquely mapped reads/length of transcribed region) were calculated on the basis of the mapped reads on the rice genome. Transcriptional density and expression level were significantly lower in Cen5 than in the average of the other chromosomal regions. Moreover, transcriptional density in Cen5 was significantly lower on the short arm than on the long arm; the distribution of transcriptional density was asymmetric. The genomic sequence of Cen5 has been integrated into the most updated reference rice genome sequence constructed by the International Rice Genome Sequencing Project. PMID:22639581

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

    ERIC Educational Resources Information Center

    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…

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

    SciTech Connect

    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.

  8. GENE LINKAGE MAPPING OF THE PORCINE CHROMOSOME X REGION HARBOURING QTL FOR FAT DEPOSITION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The QTL for backfat thickness and intramuscular fat content on SSCX is well documented in Meishan x Western breed pedigrees. The QTL has been mapped to the chromosome region between microsatellites SW2456 and SW1943. In the French pedigree with more than 1,100 F2 animals the QTL mapped at position 7...

  9. The Drosophila suppressor of underreplication protein binds to late-replicating regions of polytene chromosomes.

    PubMed Central

    Makunin, I V; Volkova, E I; Belyaeva, E S; Nabirochkina, E N; Pirrotta, V; Zhimulev, I F

    2002-01-01

    In many late-replicating euchromatic regions of salivary gland polytene chromosomes, DNA is underrepresented. A mutation in the SuUR gene suppresses underreplication and leads to normal levels of DNA polytenization in these regions. We identified the SuUR gene and determined its structure. In the SuUR mutant stock a 6-kb insertion was found in the fourth exon of the gene. A single SuUR transcript is present at all stages of Drosophila development and is most abundant in adult females and embryos. The SuUR gene encodes a protein of 962 amino acids whose putative sequence is similar to the N-terminal part of SNF2/SWI2 proteins. Staining of salivary gland polytene chromosomes with antibodies directed against the SuUR protein shows that the protein is localized mainly in late-replicating regions and in regions of intercalary and pericentric heterochromatin. PMID:11901119

  10. XY chromosome nondisjunction in man is associated with diminished recombination in the pseudoautosomal region.

    PubMed Central

    Hassold, T J; Sherman, S L; Pettay, D; Page, D C; Jacobs, P A

    1991-01-01

    To assess the possible association between aberrant recombination and XY chromosome nondisjunction, we compared pseudoautosomal region recombination rates in male meiosis resulting in 47,XXY offspring with those resulting in 46,XY and 46,XX offspring. Forty-one paternally derived 47,XXYs and their parents were tested at six polymorphic loci spanning the pseudoautosomal region. We were able to detect crossing-over in only six of 39 cases informative for the telomeric DXYS14/DXYS20 locus. Subsequently, we used the data to generate a genetic linkage map of the pseudoautosomal region and found it to be significantly shorter than the normal male map of the region. From these analyses we conclude that most paternally derived 47,XXYs result from meiosis in which the X and Y chromosomes did not recombine. Images Figure 1 PMID:1867189

  11. Mapping the chromosome 16 cadherin gene cluster to a minimal deleted region in ductal breast cancer.

    PubMed

    Chalmers, I J; Aubele, M; Hartmann, E; Braungart, E; Werner, M; Höfler, H; Atkinson, M J

    2001-04-01

    The cadherin family of cell adhesion molecules has been implicated in tumor metastasis and progression. Eight family members have been mapped to the long arm of chromosome 16. Using radiation hybrid mapping, we have located six of these genes within a cluster at 16q21-q22.1. In invasive lobular carcinoma of the breast frequent LOH and accompanying mutation affect the CDH1 gene, which is a member of this chromosome 16 gene cluster. CDH1 LOH also occurs in invasive ductal carcinoma, but in the absence of gene mutation. The proximity of other cadherin genes to 16q22.1 suggests that they may be affected by LOH in invasive ductal carcinomas. Using the mapping data, microsatellite markers were selected which span regions of chromosome 16 containing the cadherin genes. In breast cancer tissues, a high rate of allelic loss was found over the gene cluster region, with CDH1 being the most frequently lost marker. In invasive ductal carcinoma a minimal deleted region was identified within part of the chromosome 16 cadherin gene cluster. This provides strong evidence for the existence of a second 16q22 suppressor gene locus within the cadherin cluster. PMID:11343777

  12. Commonly deleted region on the long arm of chromosome 7 in differentiated adenocarcinoma of the stomach.

    PubMed Central

    Nishizuka, S.; Tamura, G.; Terashima, M.; Satodate, R.

    1997-01-01

    Loss of heterozygosity (LOH) at several chromosomal loci is a common event in human malignancies. Frequent LOH on the long arm of chromosome 7 has been reported in various human malignancies, and investigators have identified the most common site of LOH as 7q31.1. We have identified ten chromosomal loci, including chromosome 7q, that have been shown by previous allelotype study to be sites of frequent LOH in differentiated adenocarcinoma of the stomach. In the present study, we performed a polymerase chain reaction (PCR) microsatellite analysis to define the common deleted region on 7q, using 14 polymorphic microsatellite markers in matched tumour and non-tumour DNAs from 53 patients with primary gastric carcinoma of the differentiated type. LOH at any locus on 7q occurred in 34% (18 out of 53) of the tumours. Although many tumours exhibited total or large interstitial deletions, we determined the smallest common deleted region to be at D7S480 (7q31.1). This is identical to the region identified for other human malignancies. These observations indicate that a putative tumour suppressor gene at 7q31.1 may be involved in the pathogenesis of differentiated adenocarcinoma of the stomach. Images Figure 1 PMID:9413943

  13. The organisation of repetitive sequences in the pericentromeric region of human chromosome 10.

    PubMed Central

    Jackson, M S; Slijepcevic, P; Ponder, B A

    1993-01-01

    Three satellite DNA families are present in the pericentromeric region of chromosome 10; the alpha satellite and two 5 bp satellite families defined here as satellites 2 and 3. Pulsed field gel electrophoresis (PFGE) demonstrates that these sequences are organised into five discrete arrays which are linked within a region of approximately 5.3 Megabases (Mb) of DNA. The alpha satellite is largely confined to a 2.2 Mb array which is flanked on its p arm side by two 100-150 kb satellite 3 arrays and on its q arm side by a 900 kb satellite 2 array and a further 320 kb satellite 3 array. This linear order is corroborated by fluorescent in situ hybridisation analyses. In total, these arrays account for 3.6 Mb of DNA in the pericentromeric region of chromosome 10. These data provide both physical information on sequences which may be involved in centromere function and a map across the centromere which has the potential to link yeast artificial chromosome (YAC) contigs currently being developed on both arms of this chromosome. Images PMID:8290346

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

    SciTech Connect

    Toth-Fejel, S.; Magenis, R.E.; Leff, S.

    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.

  15. Linkage disequilibrium patterns vary with chromosomal location: A case study from the von Willebrand factor region

    SciTech Connect

    Watkins, W.S.; Zenger, R.; O'Brien, E.; Jorde, L.B. ); Nyman, D. ); Eriksson, A.W. ); Renlund, M.

    1994-08-01

    Linkage disequilibrium analysis has been used as a tool for analyzing marker order and locating disease genes. Under appropriate circumstances, disequilibrium patterns reflect recombination events that have occurred throughput a population's history. As a result, disequilibrium mapping may be useful in genomic regions of <1 cM where the number of informative meioses needed to detect recombinant individuals within pedigrees is exceptionally high. Its utility for refining target areas for candidate disease genes before initiating chromosomal walks and cloning experiments will be enhanced as the relationship between linkage disequilibrium and physical distance is better understood. To address this issue, the authors have characterized linkage disequilibrium in a 144-kb region of the von Willebrand factor gene on chromosome 12. Sixty CEPH and 12 von Willebrand disease families were genotypes for five PCR-based markers, which include two microsatellite repeats and three single-base-pair substitutions. Linkage disequilibrium and physical distance between polymorphisms are highly correlated (r[sub m] = -.76; P<.05) within this region. None of the five markers showed significant disequilibrium with the von Willebrand disease phenotype. The linkage disequilibrium/physical distance relationship was also analyzed as a function of chromosomal location for this and eight previously characterized regions. This analysis revealed a general trend in which linkage disequilibrium dissipates more rapidly with physical distance in telomeric regions than in centromeric regions. This trend is consistent with higher recombination rates near telomeres. 52 refs., 3 figs., 4 tabs.

  16. [Morphological diversity of centromere regions in polytene chromosomes of blackflies (Diptera, Simulidae)].

    PubMed

    Chubareva, L A; Petrova, N A; Kachvorian, E A

    2003-01-01

    Karyotypes of more than 120 species of 33 genera of the Palearctic blackflies (Simuliidae) were studied on squashed acetoorcein stained preparations of salivary gland polytene chromosomes in larvae. In the course of evolution of the family, a significant complication was noticed in the morphology of centromere regions of polytene chromosomes. In plesiomorphic species, centromeres are not pronounced morphologically and the general picture does not differ from that of other bands and interbands of the polytene chromosome. In species with apomorphic characters, a distinct precentromeric heterochromatin appears, whose manifestation is responsible for morphological diversity of centromere zones in polytene chromosomes. They are represented either by conspicuous slightly thickened heterochromatic bands or by large amplified blocks of heterochromatin or puff-like structure, being considerably extended as a result of despiralization of precentromeric heterochromatin. There are species, which more commonly lack chromocentre and their chromosomes are separated. Some other species have ectopic contacts between pricentromeric heterochromatin. In some species, this heterochromatin is organized as a compact chromocentre. This has been found only in representatives of southern latitudes, most frequently in evolutionarily young species with narrow specialization. PMID:14520867

  17. The mechanisms determining the nucleolar-organizing regions inactivation of domestic horse chromosomes.

    PubMed

    Slota, E; Wnuk, M; Bugno, M; Pienkowska-Schelling, A; Schelling, C; Bratus, A; Kotylak, Z

    2007-06-01

    Cytogenetic investigations of the nucleolar-organizing regions (NORs) show that there is variation in the transcriptional activity of rDNA in many organisms. As a consequence, genetic polymorphism of these regions has been detected. The aim of the present study was to evaluate the hypothetic genetic mechanisms determining the NORs polymorphism of the domestic horse chromosomes. Molecular cytogenetic analyses were carried out on Hucul horses and the following techniques were used: fluorescence in situ hybridization (FISH), telomere primed in situ synthesis (PRINS), in situ nick-translation with HpaII, silver staining (AgNOR) and C-banding technique (CBG). The obtained results suggest that variation in the number and size of silver deposits is related to the number of rDNA copies, DNA methylation and the localization of ribosomal DNA loci in telomeric regions. Moreover, we have found that chromosome pairs 28 and 31 are characterized by higher variation in the NORs number. PMID:17550359

  18. [Variations of heterochromatic chromosomal regions and chromosome abnormalities in children with autism: identification of genetic markers in autistic spectrum disorders].

    PubMed

    Vorsanova, S G; Iurov, I Iu; Demidova, I A; Voinova-Ulas, V Iu; Kravets, V S; Solov'ev, I V; Gorbachevskaia, N L; Iurov, Iu B

    2006-01-01

    In the present study, the cytogenetic and molecular cytogenetic analysis of 90 children with autism and their mothers (18 subjects) was carried out. Chromosome fragility and abnormalities were found in four cases: mos 47,XXX[98]/ 46,XX[2]; 46,XY,r(22)(p11q13); 46,XY,inv(2)(p11.2q13),16qh-; 46Y,fra(X)(q27.3)16qh-. Using C-banding and quantitative fluorescent in situ hybridization (FISH), the significantly increased incidence of heterochromatic region variation was shown in autism as compared to the controls (48 and 16%, respectively). Pericentric 9phqh inversion was not characteristic of the patients with autism whereas heterochromatic variations 1phqh, 9qh+ and 16qh- were more frequent in autism (p<0,05). Basing on the data obtained, a possible role of position effect in autism pathogenesis as well as a potential of heterochromatic region variation analysis for the search of biological markers of autistic spectrum disorders are discussed. PMID:16841485

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

    PubMed Central

    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. PMID:23671840

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

    USGS Publications Warehouse

    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.

  1. Physical mapping in the Cri du Chat region on human chromosome 5

    SciTech Connect

    Church, D.M.; Bengtsson, U.; Niebuhr, E.

    1994-09-01

    The Cri du Chat syndrome is a segmental aneusomy associated with deletions in the short arm of human chromosome 5. More specifically, the cytogenetic band 5p15.2 must be deleted in order to manifest the typical phenotypic signs. We have studied several cell lines from individuals who have chromosomal abnormalities within this cytogenetic band but who do not have typical Cri du Chat syndrome. In fact, several individual studied have no discernible features of this syndrome. Using fluorescent in situ hybridization (FISH) analysis and PCR analysis on somatic cell hybrids we have mapped the breakpoints relative to each other within this band. There is a great degree of phenotypic heterogeneity between several of the patients, even those which share common breakpoints. This heterogeneity makes it very difficult to narrow the region of interest to a very small (<1 Mb) region. In order to more thoroughly analyze this region, we have assembled a yeast artificial chromosome (YAC) contig of part of this region. This contig has been analyzed for STS content and covers approximately a 1.5-2.0 Mb region within 5p15.2. In addition, we have constructed a radiation hybrid map of the region. The YACs contained within the minimal contig have been used as hybridization probes to isolate corresponding cosmid clones within the region of interest. These cosmids, in turn, are being utilized to obtain potential exons using exon amplification. Several cosmids within this region have been isolated by STS content and potential exons have been isolated from them. These exons have been used as probes to isolate cDNA clones from the region. It is our hope that isolation of genes throughout the region of interest will allow a better understanding of the etiology of Cri du Chat.

  2. Multicolor chromosome banding (MCB) with YAC/BAC-based probes and region-specific microdissection DNA libraries

    SciTech Connect

    Liehr, T.; Weise, A.; Heller, A.; Starke, H.; Mrasek, K.; Kuechler, A.; Weier, H.-U.G.; Claussen, U.

    2003-06-23

    Multicolor chromosome banding (MCB) allows the delineation of chromosomal regions with a resolution of a few mega base pairs, i.e., slightly below the size of most visible chromosome bands. Based on the hybridization of over lapping region-specific probe libraries, chromosomal subregions are hybridized with probes that fluoresce in distinct wave length intervals, so they can be assigned predefined pseudo-colors during the digital imaging and visualization process. The present study demonstrates how MCB patterns can be produced by region-specific micro dissection derived (mcd) libraries as well as collections of yeast or bacterial artificial chromosomes (YACs and BACs, respectively). We compared the efficiency of an mcd library based approach with the hybridization of collections of locus-specific probes (LSP) for fluorescent banding of three rather differently sized human chromosomes, i.e., chromosomes 2, 13, and 22. The LSP sets were comprised of 107 probes specific for chromosome 2, 82 probes for chromosome 13, and 31 probes for chromosome 22. The results demonstrated a more homogeneous coverage of chromosomes and thus, more desirable banding patterns using the microdissection library-based MCB. This may be related to the observation that chromosomes are difficult to cover completely with YAC and/or BAC clones as single-color fluorescence in situ hybridization (FISH) experiments showed. Mcd libraries, on the other hand, provide high complexity probes that work well as region specific paints, but do not readily allow positioning of break points on genetic or physical maps as required for the positional cloning of genes. Thus, combinations of mcd libraries and locus-specific large insert DNA probes appear to be the most efficient tools for high-resolution cytogenetic analyses.

  3. Physical and transcription map of a 25 Mb region on human chromosome 7 (region q21-q22)

    SciTech Connect

    Scherer, S. |; Little, S.; Vandenberg, A.

    1994-09-01

    We are interested in the q21-q22 region of chromosome 7 because of its implication in a number of diseases. This region of about 25 Mb appears to be involved in ectrodactyly/ectodermal dysplasia/cleft plate (EEC) and split hand/split foot deformity (SHFD1), as well as myelodysplastic syndrome and acute non-lymphocyte leukemia. In order to identify the genes responsible for these and other diseases, we have constructed a physical map of this region. The proximal and distal boundaries of the region were operationally defined by the microsatellite markers D7S660 and D7S692, which are about 35 cM apart. This region between these two markers could be divided into 13 intervals on the basis of chromosome breakpoints contained in somatic cell hybrids. The map positions for 43 additional microsatellite markers and 25 cloned genes were determined with respect to these intervals. A physical map based on contigs of over 250 YACs has also been assembled. While the contigs encompass all of the known genetic markers mapped to the region and almost cover the entire 25-Mb region, there are 3 gaps on the map. One of these gaps spans a set of DNA markers for which no corresponding YAC clones could be identified. To connect the two adjacent contigs we have initiated cosmid walking with a chromosome 7-specific library (Lawrence Livermore Laboratory). A tiling path of 60 contiguous YAC clones has been assembled and used for direct cDNA selection. Over 300 cDNA clones have been isolated and characterized. They are being grouped into transcription units by Northern blot analysis and screening of full-length cDNA libraries. Further, exon amplification and direct cDNA library screening with evolutionarily conserved sequences are being performed for a 1-Mb region spanning the SHFD1 locus to ensure detection of all transcribed sequences.

  4. A gene for pili annulati maps to the telomeric region of chromosome 12q.

    PubMed

    Green, Jack; Fitzpatrick, Elizabeth; de Berker, David; Forrest, Susan M; Sinclair, Rodney D

    2004-12-01

    Pili annulati (PA) is a rare hair shaft disorder characterized by discrete banding of hairs. We studied two families with PA in which the disorder segregated in an autosomal dominant fashion. All family members were clinically examined and hair samples were examined under the light microscope. In family G, of 19 individuals examined, ten were affected, over three generations. In family B, there were three affected individuals of seven examined over three generations. A genome-wide scan of family G revealed a maximum logarithm of odds (LOD) of linkage score of 3.89 at marker D12S1723 at the telomeric region of chromosome 12q. From one critical recombinant in family G, the locus was narrowed down to a 9.2 cM region between D12S367 and the end of chromosome 12q. In family B linkage at the telomeric region of chromosome 12q also revealed a maximum LOD score of 0.89 at marker D12S1723. A combined LOD score, assuming no locus heterogeneity between the families was 4.78. Frizzled 10, which is located within the region, was sequenced but we were unable to detect a mutation causing PA. This study, for the first time, identifies a genetic locus for PA. PMID:15610516

  5. Fluorescent in situ hybridization shows DIPLOSPOROUS located on one of the NOR chromosomes in apomictic dandelions (Taraxacum) in the absence of a large hemizygous chromosomal region.

    PubMed

    Vašut, Radim J; Vijverberg, Kitty; van Dijk, Peter J; de Jong, Hans

    2014-11-01

    Apomixis in dandelions (Taraxacum: Asteraceae) is encoded by two unlinked dominant loci and a third yet undefined genetic factor: diplosporous omission of meiosis (DIPLOSPOROUS, DIP), parthenogenetic embryo development (PARTHENOGENESIS, PAR), and autonomous endosperm formation, respectively. In this study, we determined the chromosomal position of the DIP locus in Taraxacum by using fluorescent in situ hybridization (FISH) with bacterial artificial chromosomes (BACs) that genetically map within 1.2-0.2 cM of DIP. The BACs showed dispersed fluorescent signals, except for S4-BAC 83 that displayed strong unique signals as well. Under stringent blocking of repeats by C0t-DNA fragments, only a few fluorescent foci restricted to defined chromosome regions remained, including one on the nucleolus organizer region (NOR) chromosomes that contains the 45S rDNAs. FISH with S4-BAC 83 alone and optimal blocking showed discrete foci in the middle of the long arm of one of the NOR chromosomes only in triploid and tetraploid diplosporous dandelions, while signals in sexual diploids were lacking. This agrees with the genetic model of a single dose, dominant DIP allele, absent in sexuals. The length of the DIP region is estimated to cover a region of 1-10 Mb. FISH in various accessions of Taraxacum and the apomictic sister species Chondrilla juncea, confirmed the chromosomal position of DIP within Taraxacum but not outside the genus. Our results endorse that, compared to other model apomictic species, expressing either diplospory or apospory, the genome of Taraxacum shows a more similar and less diverged chromosome structure at the DIP locus. The different levels of allele sequence divergence at apomeiosis loci may reflect different terms of asexual reproduction. The association of apomeiosis loci with repetitiveness, dispersed repeats, and retrotransposons commonly observed in apomictic species may imply a functional role of these shared features in apomictic reproduction, as is

  6. Using radiation hybrids to generate region-specific markers for human chromosome 9

    SciTech Connect

    Britt, D.E.; Mark, H.F.L.; Nebres, M.

    1994-09-01

    The production of sequence tagged sites and polymorphic markers is an important step in generating a physical map of the human genome and identifying loci involved in genetic diseases. Our work involves the physical mapping of the short arm of human chromosome 9, the site of at least one tumor supressor gene, as well as the locus involved in cartilage hair hypoplasia. Our goal is to increase the number of markers available for 9p, using a panel of radiation hybrids we have constructed and characterized. The hybrids were generated from a monochromosomal hybrid that contains human chromosome 9 marked with a retroviral vector. Radiation hybrids were produced that contain overlapping regions of the chromosome surrounding the site of retroviral integration. In order to generate markers specific for the short arm, Alu-PCR products from a radiation hybrid containing only 9p were cloned. Clones were mapped back to a subpanel of hybrids and grouped into intervals. By using a hybrid subpanel containing overlapping portions 9p, we are able to identify clones from defined regions. DNA from the clones was sequenced and this information used to generate sequence tagged sites. We have also developed a number of new polymorphic markers, taking advantage of the high degree of polymorphism of the 3{prime} end of each Alu sequence. For each polymorphic marker, a specific primer was designed from the cloned DNA and then paired with an Alu primer. These primer pairs were used to amplify DNA from unrelated individuals, in order to identify primer sets that detect useful polymorphisms. Both the STS and polymorphic markers will be extremely useful in the construction of a physical map of chromosome 9, and in the identification of genes on the short arm of the chromosome.

  7. Genetic Mapping of the BRCA1 Region on Chromosome 17q21

    PubMed Central

    Albertsen, Hans; Plaetke, Rosemarie; Ballard, Linda; Fujimoto, Esther; Connolly, Judith; Lawrence, Elizabeth; Rodriguez, Pilar; Robertson, Margaret; Bradley, Paige; Milner, Bruce; Fuhrman, David; Marks, Andy; Sargent, Robert; Cartwright, Peter; Matsunami, Nori; White, Ray

    1994-01-01

    Chromosome 17q21 harbors a gene (BRCA1) associated with a hereditary form of breast cancer. As a step toward identification of this gene itself we developed a number of simple-sequence-repeat (SSR) markers for chromosome 17 and constructed a high-resolution genetic map of a 40-cM region around 17q21. As part of this effort we captured genotypes from five of the markers by using an ABI sequencing instrument and stored them in a locally developed database, as a step toward automated genotyping. In addition, YACs that physically link some of the SSR markers were identified. The results provided by this study should facilitate physical mapping of the BRCA1 region and isolation of the BRCA1 gene. ImagesFigure 2Figure 1 PMID:8116621

  8. Comparative Genomic Sequence Analysis of the Human Chromosome 21 Down Syndrome Critical Region

    PubMed Central

    Toyoda, Atsushi; Noguchi, Hideki; Taylor, Todd D.; Ito, Takehiko; Pletcher, Mathew T.; Sakaki, Yoshiyuki; Reeves, Roger H.; Hattori, Masahira

    2002-01-01

    Comprehensive knowledge of the gene content of human chromosome 21 (HSA21) is essential for understanding the etiology of Down syndrome (DS). Here we report the largest comparison of finished mouse and human sequence to date for a 1.35-Mb region of mouse chromosome 16 (MMU16) that corresponds to human chromosome 21q22.2. This includes a portion of the commonly described “DS critical region,” thought to contain a gene or genes whose dosage imbalance contributes to a number of phenotypes associated with DS. We used comparative sequence analysis to construct a DNA feature map of this region that includes all known genes, plus 144 conserved sequences ≥100 bp long that show ≥80% identity between mouse and human but do not match known exons. Twenty of these have matches to expressed sequence tag and cDNA databases, indicating that they may be transcribed sequences from chromosome 21. Eight putative CpG islands are found at conserved positions. Models for two human genes, DSCR4 and DSCR8, are not supported by conserved sequence, and close examination indicates that low-level transcripts from these loci are unlikely to encode proteins. Gene prediction programs give different results when used to analyze the well-conserved regions between mouse and human sequences. Our findings have implications for evolution and for modeling the genetic basis of DS in mice. [Sequence data described in this paper have been submitted to the DDBJ/GenBank under accession nos. AP003148 through AP003158, and AB066227. Supplemental material is available at http://www.genome.org.] PMID:12213769

  9. Identification of a 1.1-Mb region for a carcass weight QTL onbovine Chromosome 14.

    PubMed

    Mizoshita, Kazunori; Takano, Atsushi; Watanabe, Toshio; Takasuga, Akiko; Sugimoto, Yoshikazu

    2005-07-01

    We previously mapped a quantitative trait locus for carcass weight, designated Carcass Weight-1 (CW-1), to bovine Chromosome 14 using a purebred Wagyu pedigree based on progeny design analysis. To refine the critical region within 8.1 cM flanked by microsatellites BMS1941 and INRA094, we constructed a bacterial artificial chromosome (BAC) contig composed of 60 tiled BAC clones and prepared a high-density physical map including 80 microsatellites, of which 55 were developed in this study. We conducted linkage disequilibrium (LD) mapping in the CW-1 region with 47 microsatellites using paternal half-sib pedigrees whose sires exhibited homozygous CW-1 Q alleles in the region. The LD mapping study significantly narrowed the CW-1 locus to the 1.1-Mb region between microsatellites DIK7012 and DIK7020. Finally, we surveyed the 1.1-Mb-region genotypes of 1700 steers from 11 bulls having -/-, Q/-, or Q/Q alleles in the region, and we examined the effect of the CW-1 Q allele on carcass weight. The presence of the first Q increased carcass weight by 23.6 kg (95% confidence interval [CI], 17.6-29.5 kg), and the second Q increased carcass weight an additional 15.2 kg (95% CI, 10.7-19.7 kg). These results indicate the presence of a gene responsible for carcass weight within the 1.1-Mb region. PMID:16151698

  10. Modular sequence elements associated with origin regions in eukaryotic chromosomal DNA.

    PubMed Central

    Dobbs, D L; Shaiu, W L; Benbow, R M

    1994-01-01

    We have postulated that chromosomal replication origin regions in eukaryotes have in common clusters of certain modular sequence elements (Benbow, Zhao, and Larson, BioEssays 14, 661-670, 1992). In this study, computer analyses of DNA sequences from six origin regions showed that each contained one or more potential initiation regions consisting of a putative DUE (DNA unwinding element) aligned with clusters of SAR (scaffold associated region), and ARS (autonomously replicating sequence) consensus sequences, and pyrimidine tracts. The replication origins analyzed were from the following loci: Tetrahymena thermophila macronuclear rDNA gene, Chinese hamster ovary dihydrofolate reductase amplicon, human c-myc proto-oncogene, chicken histone H5 gene, Drosophila melanogaster chorion gene cluster on the third chromosome, and Chinese hamster ovary rhodopsin gene. The locations of putative initiation regions identified by the computer analyses were compared with published data obtained using diverse methods to map initiation sites. For at least four loci, the potential initiation regions identified by sequence analysis aligned with previously mapped initiation events. A consensus DNA sequence, WAWTTDDWWWDHWGWHMAWTT, was found within the potential initiation regions in every case. An additional 35 kb of combined flanking sequences from the six loci were also analyzed, but no additional copies of this consensus sequence were found. Images PMID:8041609

  11. Minute supernumerary ring chromosome 22 associated with cat eye syndrome: Further delineation of the critical region

    SciTech Connect

    Mears, A.J.; McDermid, H.E.; El-Shanti, H.

    1995-09-01

    Cat eye syndrome (CES) is typically associated with a supernumerary bisatellited marker chromosome (inv dup 22pter-22q11.2) resulting in four copies of this region. We describe an individual showing the inheritance of a minute supernumerary double ring chromosome 22, which resulted in expression of all cardinal features of CES. The size of the ring was determined by DNA dosage analysis and FISH analysis for five loci mapping to 22q11.2. The probes to the loci D22S9, D22S43, and ATP6E were present in four copies, whereas D22S57 and D22S181 were present in two copies. This finding further delineates the distal boundary of the critical region of CES, with ATP6E being the most distal duplicated locus identified. The phenotypically normal father and grandfather of the patient each had a small supernumerary ring chromosome and demonstrated three copies for the loci D22S9, D22S43, and ATP6E. Although three copies of this region have been reported in other cases with CES features, it is possible that the presence of four copies leads to greater susceptibility. 35 refs., 4 figs., 2 tabs.

  12. Y chromosome azoospermia factor region microdeletions and transmission characteristics in azoospermic and severe oligozoospermic patients

    PubMed Central

    Yu, Xiao-Wei; Wei, Zhen-Tong; Jiang, Yu-Ting; Zhang, Song-Ling

    2015-01-01

    Spermatogenesis is an essential reproductive process that is regulated by many Y chromosome specific genes. Most of these genes are located in a specific region known as the azoospermia factor region (AZF) in the long arm of the human Y chromosome. AZF microdeletions are recognized as the most frequent structural chromosomal abnormalities and are the major cause of male infertility. Assisted reproductive techniques (ART) such as intra-cytoplasmic sperm injection (ICSI) and testicular sperm extraction (TESE) can overcome natural fertilization barriers and help a proportion of infertile couples produce children; however, these techniques increase the transmission risk of genetic defects. AZF microdeletions and their associated phenotypes in infertile males have been extensively studied, and different AZF microdeletion types have been identified by sequence-tagged site polymerase chain reaction (STS-PCR), suspension array technology (SAT) and array-comparative genomic hybridization (aCGH); however, each of these approaches has limitations that need to be overcome. Even though the transmission of AZF microdeletions has been reported worldwide, arguments correlating ART and the incidence of AZF microdeletions and explaining the occurrence of de novo deletions and expansion have not been resolved. Using the newest findings in the field, this review presents a systematic update concerning progress in understanding the functions of AZF regions and their associated genes, AZF microdeletions and their phenotypes and novel approaches for screening AZF microdeletions. Moreover, the transmission characteristics of AZF microdeletions and the future direction of research in the field will be specifically discussed. PMID:26628946

  13. Analysis of tandem gene copies in maize chromosomal regions reconstructed from long sequence reads

    PubMed Central

    Dong, Jiaqiang; Feng, Yaping; Kumar, Dibyendu; Zhang, Wei; Zhu, Tingting; Luo, Ming-Cheng; Messing, Joachim

    2016-01-01

    Haplotype variation not only involves SNPs but also insertions and deletions, in particular gene copy number variations. However, comparisons of individual genomes have been difficult because traditional sequencing methods give too short reads to unambiguously reconstruct chromosomal regions containing repetitive DNA sequences. An example of such a case is the protein gene family in maize that acts as a sink for reduced nitrogen in the seed. Previously, 41–48 gene copies of the alpha zein gene family that spread over six loci spanning between 30- and 500-kb chromosomal regions have been described in two Iowa Stiff Stalk (SS) inbreds. Analyses of those regions were possible because of overlapping BAC clones, generated by an expensive and labor-intensive approach. Here we used single-molecule real-time (Pacific Biosciences) shotgun sequencing to assemble the six chromosomal regions from the Non-Stiff Stalk maize inbred W22 from a single DNA sequence dataset. To validate the reconstructed regions, we developed an optical map (BioNano genome map; BioNano Genomics) of W22 and found agreement between the two datasets. Using the sequences of full-length cDNAs from W22, we found that the error rate of PacBio sequencing seemed to be less than 0.1% after autocorrection and assembly. Expressed genes, some with premature stop codons, are interspersed with nonexpressed genes, giving rise to genotype-specific expression differences. Alignment of these regions with those from the previous analyzed regions of SS lines exhibits in part dramatic differences between these two heterotic groups. PMID:27354512

  14. Genomic structure and evolution of the ancestral chromosome fusion site in 2q13-2q14.1 and paralogous regions on other human chromosomes.

    PubMed

    Fan, Yuxin; Linardopoulou, Elena; Friedman, Cynthia; Williams, Eleanor; Trask, Barbara J

    2002-11-01

    Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13-2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%-99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ~100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans. PMID:12421751

  15. Chromosomal protein HMG-14 gene maps to the Down syndrome region of human chromosome 21 and is overexpressed in mouse trisomy 16

    SciTech Connect

    Pash, J.; Popescu, N.; Matocha, M.; Rapoport, S.; Bustin, M. )

    1990-05-01

    The gene for human high-mobility-group (HMG) chromosomal protein HMG-14 is located in region 21q22.3, a region associated with the pathogenesis of Down syndrome, one of the most prevalent human birth defects. The expression of this gene is analyzed in mouse embryos that are trisomic in chromosome 16 and are considered to be an animal model for Down syndrome. RNA blot-hybridization analysis and detailed analysis of HMG-14 protein levels indicate that mouse trisomy 16 embryos have approximately 1.5 times more HMG-14 mRNA and protein than their normal littermates, suggesting a direct gene dosage effect. The HMG-14 gene may be an additional marker for the Down syndrome. Chromosomal protein HMG-14 is a nucleosomal binding protein that may confer distinct properties to the chromatin structure of transcriptionally active genes and therefore may be a contributing factor in the etiology of the syndrome.

  16. Exclusion of primary congenital glaucoma (PCG) from two candidate regions of chromosomes 1 and 6

    SciTech Connect

    Sarfarazi, M.; Akarsu, A.N.; Barsoum-Homsy, M.

    1994-09-01

    PCG is a genetically heterogeneous condition in which a significant proportion of families inherit in an autosomally recessive fashion. Although association of PCG with chromosomal abnormalities has been repeatedly reported in the literature, the chromosomal location of this condition is still unknown. Therefore, this study is designed to identify the chromosomal location of the PCG locus by positional mapping. We have identified 80 PCG families with a total of 261 potential informative meiosis. A group of 19 pedigrees with a minimum of 2 affected children in each pedigree and consanguinity in most of the parental generation were selected as our initial screening panel. This panel consists of a total of 44 affected and 93 unaffected individuals giving a total of 99 informative meiosis, including 5 phase-known. We used polymerase chain reaction (PCR), denaturing polyacrylamide gels and silver staining to genotype our families. We first screened for markers on 1q21-q31, the reported location for juvenile primary open-angle glaucoma and excluded a region of 30 cM as the likely site for the PCG locus. Association of PCG with both ring chromosome 6 and HLA-B8 has also been reported. Therefore, we genotyped our PCG panel with PCR applicable markers from 6p21. Significant negative lod scores were obtained for D6S105 (Z = -18.70) and D6S306 (Z = -5.99) at {theta}=0.001. HLA class 1 region has also contained one of the tubulin genes (TUBB) which is an obvious candidate for PCG. Study of this gene revealed a significant negative lod score with PCG (Z = -16.74, {theta}=0.001). A multipoint linkage analysis of markers in this and other regions containing the candidate genes will be presented.

  17. Physical map and functional studies of the juxtacentromeric region of chromosome 13

    SciTech Connect

    Dupont, J.M.; Dode, C.; Piccolo, F.

    1994-09-01

    The structure of the juxtacentromeric region of chromosome 13 has been analyzed in order to investigate a putative position effect of the centromeric heterochromatin and to provide a physical landmark needed in the positional cloning of the autosomal recessive muscular dystrophy gene (SCARMD1). A genomic fragment corresponding to the insertion of a L1 sequence in juxtacentromeric block of satellite 3 has been cloned after PCR amplification of a somatic hybrid containing human chromosome 13 only. The sequence defines a new family of satellite 3 DNA and belongs to the heterochromatin region of chromosome 13. Human satellite 2 and 3 sequences are methylated in every cell except in the germ cell line and extra-embryonic tissues. In ICF syndrome, the alteration of the chromatin structure is associated with a deficit or complete absence of methylation of satellite 2 and 3 sequences. Cloning junctional euchromatic sequences immediately adjacent to heterochromatin will help to characterize the methylation pattern of non-satellite heterochromatized sequences in normal cells and methylation-deficient patients.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25644606

  19. Genetic linkage of mild pseudoachondroplasia (PSACH) to markers in the pericentromeric region of chromosome 19

    SciTech Connect

    Briggs, M.D.; Rasmussen, M.; Garber, P.; Rimoin, D.L.; Cohn, D.H. ); Weber, J.L. ); Yuen, J.; Reinker, K. )

    1993-12-01

    Pseudoachondroplasia (PSACH) is a dominantly inherited form of short-limb dwarfism characterized by dysplastic changes in the spine, epiphyses, and metaphyses and early onset osteoarthropathy. Chondrocytes from affected individuals accumulate an unusual appearing material in the rough endoplasmic reticulum, which has led to the hypothesis that a structural abnormality in a cartilage-specific protein produces the phenotype. The authors recently identified a large family with a mild form of pseudoachondroplasia. By genetic linkage to a dinucleotide repeat polymorphic marker (D19S199), they have localized the disease gene to chromosome 19 (maximum lod score of 7.09 at a recombination fraction of 0.03). Analysis of additional markers and recombinations between the linked markers and the phenotype suggests that the disease gene resides within a 6.3-cM interval in the immediate pericentromeric region of the chromosome. 39 refs., 2 figs., 1 tab.

  20. Physical mapping of the congenital chloride diarrhea gene region in human chromosome 7

    SciTech Connect

    Kere, J.; Hoeglund, P.; Haila, S.

    1994-09-01

    The gene for congenital chloride diarrhea (CLD; MIM 214700) has been mapped to human chromosome 7 by a linkage study in Finnish families. The markers closest to the gene are D7S496 and D7S501, both with zero recombination fraction. In order to physically map the region and facilitate positional cloning, altogether 25 YAC clones have been isolated from the Washington University chromosome 7 collection of YACs. The clones form 2 contigs, 700 to 900 kb in size, around D7S496 and D7SS01. One YAC from the CEPH collection that bridges these contigs has been identified, but the link remains unconfirmed. Rare-cutter restriction mapping has identified as least 3 CpG islands within 50 to 200 kb of D7S496, supposed to map closest to CLD on the basis of linkage disequilibrium studies. Isolation of candidate cDNAs is in progress.

  1. A second gene for cerulean cataracts maps to the {beta} crystallin region on chromosome 22

    SciTech Connect

    Kramer, P.; Yount, J.; Lovrien, E.

    1996-08-01

    Cogenital cataracts are one of the most common major eye abnormalities and often lead to blindness in infants. At least a third of all cases are familial. Within this group, highly penetrant, autosomal dominant forms of congenital cataracts (ADCC) are most common. ADCC is a genetically heterogeneous group of disorders, in which at least eight different loci have been identified for nine clinically distinct forms. Among these, Armitage et al. mapped a gene for cerulean blue cataracts to chromosome 17q24. Bodker et al. described a large family with cerulean blue cataracts, in which the affected daughter of affected first cousins was presumed to be homozygous for the purported gene. We report linkage in this family to the region on chromosome 22q that includes two {beta} crystallin genes (CRYBB2, CRYBB3) and one pseudogene (CRYBB2P1). The affected female in question is homozygous at all markers. 25 refs., 1 fig., 1 tab.

  2. Genetic Analysis of the Adenosine3 (Gart) Region of the Second Chromosome of Drosophila Melanogaster

    PubMed Central

    Tiong, SYK.; Nash, D.

    1990-01-01

    The Gart gene of Drosophila melanogaster is known, from molecular biological evidence, to encode a polypeptide that serves three enzymatic functions in purine biosynthesis. It is located in polytene chromosome region 27D. One mutation in the gene (ade3(1)) has been described previously. We report here forty new ethyl methanesulfonate-induced mutations selected against a synthetic deficiency of the region from 27C2-9 to 28B3-4. The mutations were characterized cytogenetically and by complementation analysis. The analysis apparently identifies 12 simple complementation groups. In addition, two segments of the chromosome exhibit complex complementation behavior. The first, the 28A region, gave three recessive lethals and also contains three known visible mutants, spade (spd), Sternopleural (sp) and wingless (wg); a complex pattern of genetic interaction in the region incorporates both the new and the previously known mutants. The second region is at 27D, where seven extreme semilethal mutations give a complex complementation pattern that also incorporates ade3(1). Since ade3(1) is defective in one of the enzymatic functions encoded in the Gart gene, we assume the other seven also affect the gene. The complexity of the complementation pattern presumably reflects the functional complexity of the gene product. The phenotypic effects of the mutants at 27D are very similar to those described for ade2 mutations, which also interrupt purine biosynthesis. PMID:2108904

  3. Construction of a yeast artifical chromosome contig spanning the spinal muscular atrophy disease gene region

    SciTech Connect

    Kleyn, P.W.; Wang, C.H.; Vitale, E.; Pan, J.; Ross, B.M.; Grunn, A.; Palmer, D.A.; Warburton, D.; Brzustowicz, L.M.; Gilliam, T.G. ); Lien, L.L.; Kunkel, L.M. )

    1993-07-15

    The childhood spinal muscular atrophies (SMAs) are the most common, serious neuromuscular disorders of childhood second to Duchenne muscular dystrophy. A single locus for these disorders has been mapped by recombination events to a region of 0.7 centimorgan (range, 0.1-2.1 centimorgans) between loci D5S435 and MAP1B on chromosome 5q11.2-13.3. By using PCR amplification to screen yeast artificial chromosome (YAC) DNA pools and the PCR-vectorette method to amplify YAC ends, a YAC contig was constructed across the disease gene region. Nine walk steps identified 32 YACs, including a minimum of seven overlapping YAC clones (average size, 460 kb) that span the SMA region. The contig is characterized by a collection of 30 YAC-end sequence tag sites together with seven genetic markers. The entire YAC contig spans a minimum of 3.2 Mb; the SMA locus is confined to roughly half of this region. Microsatellite markers generated along the YAC contig segregate with the SMA locus in all families where the flanking markers (D5S435 and MAP1B) recombine. Construction of a YAC contig across the disease gene region is an essential step in isolation of the SMA-encoding gene. 26 refs., 3 figs., 1 tab.

  4. Nonrandom chromosomal aberrations and cytogenetic heterogeneity in gallbladder carcinomas.

    PubMed

    Gorunova, L; Parada, L A; Limon, J; Jin, Y; Hallén, M; Hägerstrand, I; Iliszko, M; Wajda, Z; Johansson, B

    1999-12-01

    Chromosome banding analysis of 11 short-term cultured gallbladder carcinomas revealed acquired clonal aberrations in seven tumors (five primary and two metastases). Three of these had one clone, whereas the remaining four were cytogenetically heterogeneous, displaying two to seven aberrant clones. Of a total of 21 abnormal clones, 18 had highly complex karyotypes and three exhibited simple numerical deviations. Double minutes and homogeneously staining regions were observed in one and two carcinomas, respectively. To characterize the karyotypic profile of gallbladder cancer more precisely, we have combined the present findings with our three previously reported cases, thereby providing the largest cytogenetic database on this tumor type to date. A total of 287 chromosomal breakpoints were identified, 251 of which were found in the present study. Chromosome 7 was rearranged most frequently, followed by chromosomes 1, 3, 11, 6, 5, and 8. The bands preferentially involved were 1p32, 1p36, 1q32, 3p21, 6p21, 7p13, 7q11, 7q32, 19p13, 19q13, and 22q13. Nine recurrent abnormalities could, for the first time, be identified in gallbladder carcinoma: del(3)(p13), i(5)(p10), del(6)(q13), del(9)(p13), del(16)(q22), del(17)(p11), i(17)(q10), del(19)(p13), and i(21)(q10). The most common partial or whole-arm gains involved 3q, 5p, 7p, 7q, 8q, 11q, 13q, and 17q, and the most frequent partial or whole-arm losses affected 3p, 4q, 5q, 9p, 10p, 10q, 11p, 14p, 14q, 15p, 17p, 19p, 21p, 21q, and Xp. These chromosomal aberrations and imbalances provide some starting points for molecular analyses of genomic regions that may harbor genes of pathogenetic importance in gallbladder carcinogenesis. Genes Chromosomes Cancer 26:312-321, 1999. PMID:10534766

  5. A physical map of the polytenized region (101EF-102F) of chromosome 4 in Drosophila melanogaster.

    PubMed

    Locke, J; Podemski, L; Aippersbach, N; Kemp, H; Hodgetts, R

    2000-07-01

    Chromosome 4, the smallest autosome ( approximately 5 Mb in length) in Drosophila melanogaster contains two major regions. The centromeric domain ( approximately 4 Mb) is heterochromatic and consists primarily of short, satellite repeats. The remaining approximately 1.2 Mb, which constitutes the banded region (101E-102F) on salivary gland polytene chromosomes and contains the identified genes, is the region mapped in this study. Chromosome walking was hindered by the abundance of moderately repeated sequences dispersed along the chromosome, so we used many entry points to recover overlapping cosmid and BAC clones. In situ hybridization of probes from the two ends of the map to polytene chromosomes confirmed that the cloned region had spanned the 101E-102F interval. Our BAC clones comprised three contigs; one gap was positioned distally in 102EF and the other was located proximally at 102B. Twenty-three genes, representing about half of our revised estimate of the total number of genes on chromosome 4, were positioned on the BAC contigs. A minimal tiling set of the clones we have mapped will facilitate both the assembly of the DNA sequence of the chromosome and a functional analysis of its genes. PMID:10880479

  6. Physical mapping of DNA markers in the q13-q22 region of the human X chromosome

    SciTech Connect

    Philippe, C.; Chery, M.; Abbadi, N.; Gilgenkrantz, S. ); Cremers, F.P.M.; Bach, I.; Ropers, H.H. )

    1993-07-01

    DNA probe screening of somatic cell hybrids derived from females with X; autosome translocations has enabled definition of eight new breakpoints within the Xq13-q22 region. Together with other X-chromosome rearrangements that have been described earlier, these breakpoints subdivide the Xq21-q22 region into 20 intervals. This panel refines the physical assignment of 40 probes in the Xq21-q22 segment. Thus, these X-chromosome rearrangements are useful tools for ordering X-linked markers and genes on the proximal long arm of the human X chromosome. 26 refs., 3 figs., 3 tabs.

  7. Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes

    SciTech Connect

    Kelley-Clarke, Brenna; Ballestas, Mary E.; Komatsu, Takashi; Kaye, Kenneth M. . E-mail: kkaye@rics.bwh.harvard.edu

    2007-01-20

    The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) tethers KSHV terminal repeat (TR) DNA to mitotic chromosomes to efficiently segregate episomes to progeny nuclei. LANA contains N- and C-terminal chromosome binding regions. We now show that C-terminal LANA preferentially concentrates to paired dots at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes through residues 996-1139. Deletions within C-terminal LANA abolished both self-association and chromosome binding, consistent with a requirement for self-association to bind chromosomes. A deletion abolishing TR DNA binding did not affect chromosome targeting, indicating LANA's localization is not due to binding its recognition sequence in chromosomal DNA. LANA distributed similarly on human and non-human mitotic chromosomes. These results are consistent with C-terminal LANA interacting with a cell factor that concentrates at pericentromeric and peri-telomeric regions of mitotic chromosomes.

  8. Mapping of the serotonin 5-HT{sub 1D{alpha}} autoreceptor gene (HTR1D) on chromosome 1 using a silent polymorphism in the coding region

    SciTech Connect

    Ozaki, N.; Lappalainen, J.; Linnoila, M.

    1995-04-24

    Serotonin (5-HT){sub ID} receptors are 5-HT release-regulating autoreceptors in the human brain. Abnormalities in brain 5-HT function have been hypothesized in the pathophysiology of various psychiatric disorders, including obsessive-compulsive disorder, autism, mood disorders, eating disorders, impulsive violent behavior, and alcoholism. Thus, mutations occurring in 5-HT autoreceptors may cause or increase the vulnerability to any of these conditions. 5-HT{sub 1D{alpha}} and 5-HT{sub 1D{Beta}} subtypes have been previously localized to chromosomes 1p36.3-p34.3 and 6q13, respectively, using rodent-human hybrids and in situ localization. In this communication, we report the detection of a 5-HT{sub 1D{alpha}} receptor gene polymorphism by single strand conformation polymorphism (SSCP) analysis of the coding sequence. The polymorphism was used for fine scale linkage mapping of 5-HT{sub 1D{alpha}} on chromosome 1. This polymorphism should also be useful for linkage studies in populations and in families. Our analysis also demonstrates that functionally significant coding sequence variants of the 5-HT{sub 1D{alpha}} are probably not abundant either among alcoholics or in the general population. 14 refs., 1 fig., 1 tab.

  9. Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions

    PubMed Central

    2008-01-01

    Background One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY) receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes) and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishes Tetraodon nigroviridis and Takifugu rubripes. These correspond to Homo sapiens chromosomes 4, 5, 8 and 10. Results Chromosome regions with conserved synteny were identified and confirmed by phylogenetic analyses in H. sapiens, M. musculus, D. rerio, T. rubripes and T. nigroviridis. 26 gene families, including the NPY receptor genes, (plus 3 described recently by other labs) showed a tree topology consistent with duplications in early vertebrate evolution and in the actinopterygian lineage, thereby supporting expansion through block duplications. Eight gene families had complications that precluded analysis (such as short sequence length or variable number of repeated domains) and another eight families did not support block duplications (because the paralogs in these families seem to have originated in another time window than the proposed genome duplication events). RT-PCR carried out with several tissues in T. rubripes revealed that all five NPY receptors were expressed in the brain and subtypes Y2, Y4 and Y8 were also expressed in peripheral organs. Conclusion We conclude that the phylogenetic analyses and chromosomal locations of these gene families support duplications of large blocks of genes or even entire chromosomes. Thus, these results are consistent with two early vertebrate tetraploidizations forming a

  10. A Defined Terminal Region of the E. coli Chromosome Shows Late Segregation and High FtsK Activity

    PubMed Central

    Meile, Jean-Christophe; Stouf, Mathieu; Capiaux, Hervé; Mercier, Romain; Lesterlin, Christian; Hallet, Bernard; Cornet, François

    2011-01-01

    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. PMID:21799784

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

    PubMed

    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. PMID:25867454

  12. Regional assignment of the human homebox-containing gene EN1 to chromosome 2q13-q21

    SciTech Connect

    Koehler, A.; Muenke, M. ); Logan, C. ); Joyner, A.L. Samuel Lunenfeld Research Institute, Toronto )

    1993-01-01

    The human homeobox-containing genes EN1 and EN2 are closely related to the Drosophila pattern formation gene engrailed (en), which may be important in brain development, as shown by gene expression studies during mouse embryogenesis. Here, we have refined the localization of EN1 to human chromosome 2q13-q21 using a mapping panel of rodent/human cell hybrids containing different regions of chromosome 2 and a lymphoblastoid cell line with an interstitial deletion, del(2) (q21-q23.2). This regional assignment of EN1 increases to 22 the number of currently known genes on human chromosome 2q that have homologs on the proximal region of mouse chromosome 1. 15 refs., 2 figs.

  13. Transcript catalogs of human chromosome 21 and orthologous chimpanzee and mouse regions.

    PubMed

    Sturgeon, Xiaolu; Gardiner, Katheleen J

    2011-06-01

    A comprehensive representation of the gene content of the long arm of human chromosome 21 (Hsa21q) remains of interest for the study of Down syndrome, its associated phenotypic features, and mouse models. Here we compare transcript catalogs for Hsa21q, chimpanzee chromosome 21 (Ptr21q), and orthologous regions of mouse chromosomes 16, 17, and 10 for open reading frame (ORF) characteristics and conservation. The Hsa21q and mouse catalogs contain 552 and 444 gene models, respectively, of which only 162 are highly conserved. Hsa21q transcripts were used to identify orthologous exons in Ptr21q and assemble 533 putative transcripts. Transcript catalogs for all three organisms are searchable for nucleotide and amino acid sequence features of ORF length, repeat content, experimental support, gene structure, and conservation. For human and mouse comparisons, three additional summaries are provided: (1) the chromosomal distribution of novel ORF transcripts versus potential functional RNAs, (2) the distribution of species-specific transcripts within Hsa21q and mouse models of Down syndrome, and (3) the organization of sense-antisense and putative sense-antisense structures defining potential regulatory mechanisms. Catalogs, summaries, and nucleotide and amino acid sequences of all composite transcripts are available and searchable at http://gfuncpathdb.ucdenver.edu/iddrc/chr21/home.php. These data sets provide comprehensive information useful for evaluation of candidate genes and mouse models of Down syndrome and for identification of potential functional RNA genes and novel regulatory mechanisms involving Hsa21q genes. These catalogs and search tools complement and extend information available from other gene annotation projects. PMID:21400203

  14. Saudi Arabian Y-Chromosome diversity and its relationship with nearby regions

    PubMed Central

    Abu-Amero, Khaled K; Hellani, Ali; González, Ana M; Larruga, Jose M; Cabrera, Vicente M; Underhill, Peter A

    2009-01-01

    Background Human origins and migration models proposing the Horn of Africa as a prehistoric exit route to Asia have stimulated molecular genetic studies in the region using uniparental loci. However, from a Y-chromosome perspective, Saudi Arabia, the largest country of the region, has not yet been surveyed. To address this gap, a sample of 157 Saudi males was analyzed at high resolution using 67 Y-chromosome binary markers. In addition, haplotypic diversity for its most prominent J1-M267 lineage was estimated using a set of 17 Y-specific STR loci. Results Saudi Arabia differentiates from other Arabian Peninsula countries by a higher presence of J2-M172 lineages. It is significantly different from Yemen mainly due to a comparative reduction of sub-Saharan Africa E1-M123 and Levantine J1-M267 male lineages. Around 14% of the Saudi Arabia Y-chromosome pool is typical of African biogeographic ancestry, 17% arrived to the area from the East across Iran, while the remainder 69% could be considered of direct or indirect Levantine ascription. Interestingly, basal E-M96* (n = 2) and J-M304* (n = 3) lineages have been detected, for the first time, in the Arabian Peninsula. Coalescence time for the most prominent J1-M267 haplogroup in Saudi Arabia (11.6 ± 1.9 ky) is similar to that obtained previously for Yemen (11.3 ± 2) but significantly older that those estimated for Qatar (7.3 ± 1.8) and UAE (6.8 ± 1.5). Conclusion The Y-chromosome genetic structure of the Arabian Peninsula seems to be mainly modulated by geography. The data confirm that this area has mainly been a recipient of gene flow from its African and Asian surrounding areas, probably mainly since the last Glacial maximum onwards. Although rare deep rooting lineages for Y-chromosome haplogroups E and J have been detected, the presence of more basal clades supportive of the southern exit route of modern humans to Eurasian, were not found. PMID:19772609

  15. Marker development for the EPM1 region of human chromosome 21, q22.3

    SciTech Connect

    Warrington, I.A.; O`Connor, K.; Hebert, S.

    1994-09-01

    New STSs have been developed for a 0.9 Mb region of chromosome 21 that is not represented in existing YAC libraries using an efficient method that is generally applicable to any region of the genome. The region, 21q22.3, is of particular interest because the gene for progressive myoclonic epilepsy of the Unverricht-Lundborg type (EPM1) maps to this region. Until recently there were only three probes for the 1.3 Mb surrounding the EPM1 gene (D21S141,LJ112, LB2T). This very limited number of probes is problematic for obtaining clone coverage and for confirming map position of newly developed markers in the EPM1 region. To develop new markers, a somatic cell hybrid containing chromosome 21 as its only human complement (GMO8854) was digested with NOT1 and hybridized with D21S141. The fragment hybridizing with D21S141 was excised, amplified by Alu-PCR and the amplification products were cloned and sequenced. Of the fifteen clones sequenced, four were duplicates and one consisted entirely of repeat sequences. STSs were developed for the remaining ten unique clones. To determine the map position of the new STSs, quantitive PCR was used in conjunction with whole genome radiation hybrid (RH) mapping. Quantitative PCR confirmed that the STSs mapped to appropriately sized PFGE fragments and whole genome RH mapping showed that the makers were linked and gave order and distance information. Three of the new STSs are in the EPM1 region, providing additional starting points for obtaining clone coverage and gene isolation. This combination of techniques for developing markers and confirming map position is an effective approach for obtaining probes and has general applicability for regions of the genome not represented in YAC or cosmid libraries.

  16. Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q

    SciTech Connect

    Ryan, S.G.; O'Connell, P. ); Dixon, M.J. ); Nigro, M.A. ); Kelts, K.A. ); Markand, O.N. ); Shiang, R.; Wasmuth, J.J. ); Terry, J.C.

    1992-12-01

    Hyperekplexia, or startle disease (STHE), is an autosomal dominant neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to sudden, unexpected acoustic or tactile stimuli. STHE responds dramatically to the benzodiazepine drug clonazepam, which acts at gamma-aminobutyric acid type A (GABA-A) receptors. The STHE locus (STHE) was recently assigned to chromosome 5q, on the basis of tight linkage to the colony-stimulating factor 1-receptor (CSF1-R) locus in a single large family. The authors performed linkage analysis in the original and three additional STHE pedigrees with eight chromosome 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid (RH) map of the region. The results provide strong evidence for genetic locus homogeneity and assign STHE to a 5.9-cM interval defined by CSF1-R and D5S379, which are separated by an RH map distance of 74 centirays (roughly 2.2-3.7 Mb). Two polymorphic markers (D5S119 and D5S209) lie within this region, but they could not be ordered with respect to STHE. RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region. 45 refs., 4 figs., 4 tabs.

  17. Chromosome analysis of Endochironomus albipennis Meigen, 1830 and morphologically similar Endochironomus sp. (Diptera, Chironomidae) from water bodies of the Volga region, Russia

    PubMed Central

    Durnova, Natalya; Sigareva, Ludmila; Sinichkina, Olga

    2015-01-01

    Abstract Based upon the detailed chromosome map of polytene chromosomes of the eurybiont species Endochironomus albipennis Meigen, 1830, the localization of the centromere regions using a C-banding technique is defined. Chromosomal polymorphism in populations from two water bodies in the Volga region has been studied, 17 sequences are described. Polytene chromosomes of Endochironomus sp. (2n=6), having larvae morphologically similar to those of Endochironomus albipennis Meigen, 1830 (2n=6) are described for the first time. PMID:26752268

  18. Evidence for a chromosomal breakage hotspot in a 3 Mb region of Xp11.21

    SciTech Connect

    Wolff, D.J.; Willard, H.F.; Miller, A.P. |

    1994-09-01

    In order to evaluate the molecular basis for X chromosomal rearrangements, we have analyzed a series of i(Xq)s, small mar (X)s, and X;autosome translocations using fluorescence in situ hybridization (FISH). The breakpoints of 5 of 8 cytogenetically monocentric i(Xq)s and 5 of 9 Xp breakpoints resulting in mar(X)s were initially localized to Xp11.21 using cosmids for the genes ZXDA and DXS423E. In order to more precisely define the breakpoints of these abnormal Xs, as well as a series of translocated Xs, we have used yeast artificial chromosomes (YACs) derived from a contig spanning 5 Mb of DNA in Xp11.21-Xp11.22 which contains 112 YACs mapped with 51 markers, including 10 genes. Based on the FISH results, the chromosomal breakpoints could be assigned to 5 different intervals in Xp11.21. One i(Xq) has a breakpoint in the most proximal interval which is located 1 Mb from the centromere. A 300 kb region just distal to the duplicated gene ZXDB contains breakpoints for a mar(X) and a t(X;19). A third interval, which lies {approximately}300 kb further distal, contains breakpoints for 2 Incontinentia Pigmenti type 1 (IPI) translocations, 2 i(Xq)s, and 1 mar(X). One mar(X) breakpoint is localized to <200 kb of DNA proximal to DXS991, and the most distal interval, containing 2 i(Xq) breakpoints, is defined by <500 kb of DNA at the ALAS2 locus. Thus all of the breakpoints examined map to the region between ZXDA and ALAS2, which contains only 3 Mb of DNA, indicating that there is a hotspot for chromosomal breakage in proximal Xp11.21. We hypothesize that this high frequency of aberrations (representing a mutation frequency of >10{sup 5} based on the frequency of i(Xq) and mar(X)s in surveys of liveborn) may result from misalignment and/or exchanges due to the presence of inverted repeat sequences, directly duplicated gene sequences, or one or more inversion polymorphisms in the pericentromeric region.

  19. Loss of heterozygosity at chromosome 16q in prostate adenocarcinoma: identification of three independent regions.

    PubMed

    Latil, A; Cussenot, O; Fournier, G; Driouch, K; Lidereau, R

    1997-03-15

    Loss of heterozygosity (LOH) on chromosome arm 16q is one of the most consistent genetic alterations in sporadic prostate cancer and may be involved in cancer development through inactivation of tumor suppressor genes. A candidate tumor suppressor gene on this chromosome arm, CDH1 at 16q22.1, is dysregulated in prostate cancer. However, no specific deletion map has been constructed from prostate tumors to determine whether CDH1 is the potential target gene for the observed LOH on 16q. To narrow down the region of 16q loss, we constructed a detailed deletion map that incorporates CDH1. We examined the pattern of allelic imbalance in prostate tissue from 22 patients with confined prostate tumors, 22 with local extracapsular extension, and 15 with metastatic forms, using 14 CA microsatellite repeats on 16q. Thirty-five of the 59 tumors tested showed LOH for at least one marker. We found evidence of 16q monosomy in 5 cases and partial allelic loss in 30. Our data provide evidence that three different target regions on 16q might be involved in the pathogenesis of prostate cancer. The first region is telomeric and lies at 16q24.3 between markers D16S520 and D16S413; the second, the most centromeric region in the 16q22.1 band, and limited by markers D16S347 and D16S318, is close to the CDH1 gene; the third, intermediate region, at 16q23.2, is bracketed by loci D16S518 and D16S507. The rate of LOH at 16q24.3 was significantly higher in metastatic forms (80%; 12 of 15) than localized forms (32%; 7 of 22), pointing to a gene related to invasiveness in prostate cancer. PMID:9067271

  20. A Family-Based Paradigm to Identify Candidate Chromosomal Regions for Isolated Congenital Diaphragmatic Hernia

    PubMed Central

    Arrington, Cammon B.; Bleyl, Steven B.; Matsunami, Nori; Bowles, Neil E.; Leppert, Tami I.; Demarest, Bradley L.; Osborne, Karen; Yoder, Bradley A.; Byrne, Janice L.; Schiffman, Joshua D.; Null, Donald M.; DiGeronimo, Robert; Rollins, Michael; Faix, Roger; Comstock, Jessica; Camp, Nicola J.; Leppert, Mark F.; Yost, H. Joseph; Brunelli, Luca

    2012-01-01

    Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that causes high newborn mortality. Isolated or non-syndromic CDH is considered a multifactorial disease, with strong evidence implicating genetic factors. As low heritability has been reported in isolated CDH, family-based genetic methods have yet to identify the genetic factors associated with the defect. Using the Utah Population Database, we identified distantly related patients from several extended families with a high incidence of isolated CDH. Using high-density genotyping, seven patients were analyzed by homozygosity exclusion rare allele mapping (HERAM) and phased haplotype sharing (HapShare), two methods we developed to map shared chromosome regions. Our patient cohort shared three regions not previously associated with CDH, i.e. 2q11.2-q12.1, 4p13 and 7q11.2, and two regions previously involved in CDH, i.e. 8p23.1 and 15q26.2. The latter regions contain GATA4 and NR2F2, two genes implicated in diaphragm formation in mice. Interestingly, three patients shared the 8p23.1 locus and one of them also harbored the 15q26.2 segment. No coding variants were identified in GATA4 or NR2F2, but a rare shared variant was found in intron 1 of GATA4. This work shows the role of heritability in isolated CDH. Our family-based strategy uncovers new chromosomal regions possibly associated with disease, and suggests that non-coding variants of GATA4 and NR2F2 may contribute to the development of isolated CDH. This approach could speed up the discovery of the genes and regulatory elements causing multifactorial diseases, such as isolated CDH. PMID:23165927

  1. Haplotype kernel association test as a powerful method to identify chromosomal regions harboring uncommon causal variants.

    PubMed

    Lin, Wan-Yu; Yi, Nengjun; Lou, Xiang-Yang; Zhi, Degui; Zhang, Kui; Gao, Guimin; Tiwari, Hemant K; Liu, Nianjun

    2013-09-01

    For most complex diseases, the fraction of heritability that can be explained by the variants discovered from genome-wide association studies is minor. Although the so-called "rare variants" (minor allele frequency [MAF] < 1%) have attracted increasing attention, they are unlikely to account for much of the "missing heritability" because very few people may carry these rare variants. The genetic variants that are likely to fill in the "missing heritability" include uncommon causal variants (MAF < 5%), which are generally untyped in association studies using tagging single-nucleotide polymorphisms (SNPs) or commercial SNP arrays. Developing powerful statistical methods can help to identify chromosomal regions harboring uncommon causal variants, while bypassing the genome-wide or exome-wide next-generation sequencing. In this work, we propose a haplotype kernel association test (HKAT) that is equivalent to testing the variance component of random effects for distinct haplotypes. With an appropriate weighting scheme given to haplotypes, we can further enhance the ability of HKAT to detect uncommon causal variants. With scenarios simulated according to the population genetics theory, HKAT is shown to be a powerful method for detecting chromosomal regions harboring uncommon causal variants. PMID:23740760

  2. Haplotype Kernel Association Test as a Powerful Method to Identify Chromosomal Regions Harboring Uncommon Causal Variants

    PubMed Central

    Lin, Wan-Yu; Yi, Nengjun; Lou, Xiang-Yang; Zhi, Degui; Zhang, Kui; Gao, Guimin; Tiwari, Hemant K.; Liu, Nianjun

    2014-01-01

    For most complex diseases, the fraction of heritability that can be explained by the variants discovered from genome-wide association studies is minor. Although the so-called ‘rare variants’ (minor allele frequency [MAF] < 1%) have attracted increasing attention, they are unlikely to account for much of the ‘missing heritability’ because very few people may carry these rare variants. The genetic variants that are likely to fill in the ‘missing heritability’ include uncommon causal variants (MAF < 5%), which are generally untyped in association studies using tagging single-nucleotide polymorphisms (SNPs) or commercial SNP arrays. Developing powerful statistical methods can help to identify chromosomal regions harboring uncommon causal variants, while bypassing the genome-wide or exome-wide next-generation sequencing. In this work, we propose a haplotype kernel association test (HKAT) that is equivalent to testing the variance component of random effects for distinct haplotypes. With an appropriate weighting scheme given to haplotypes, we can further enhance the ability of HKAT to detect uncommon causal variants. With scenarios simulated according to the population genetics theory, HKAT is shown to be a powerful method for detecting chromosomal regions harboring uncommon causal variants. PMID:23740760

  3. Amplification of the 9p13.3 chromosomal region in prostate cancer.

    PubMed

    Latonen, Leena; Leinonen, Katri A; Grönlund, Teemu; Vessella, Robert L; Tammela, Teuvo L J; Saramäki, Outi R; Visakorpi, Tapio

    2016-08-01

    Amplification of the 9p13.3 chromosomal region occurs in a subset of prostate cancers (PCs); however, the target gene or genes of this amplification have remained unidentified. The aim of this study was to investigate the 9p13.3 amplification in more detail to identify genes that are potentially advantageous for cancer cells. We narrowed down the minimally amplified area and assessed the frequency of the 9p13.3 amplification. Of the clinical samples from untreated PCs that were examined (n = 134), 9.7% showed high-level amplification, and 32.1% showed low-level amplification. Additionally, in clinical samples from castration-resistant PCs (n = 70), high- and low-level amplification was seen in 14.3% and 44.3% of the samples, respectively. We next analyzed the protein-coding genes in this chromosomal region for both their expression in clinical PC samples as well as their potential as growth regulators in PC cells. We found that the 9p13.3 amplification harbors several genes that are able to affect the growth of PC cells when downregulated using siRNA. Of these, UBAP2 was the most prominently upregulated gene in the clinical prostate tumor samples. © 2016 Wiley Periodicals, Inc. PMID:27074291

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

    SciTech Connect

    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. Characterization of the breakpoint regions of a pericentric inversion on chromosome 6

    SciTech Connect

    Gastier, J.M.; Brody, T.; Charfat, O.

    1994-09-01

    We are attempting to clone the breakpoints of a pericentric inversion [inv(6)(p23q23.1)] which segregates in a three generation family. Phenotypic abnormalities associated with this chromosome anomaly include senori-neural hearing loss, eye (anterior segment) abnormalities, dental anomalies, and mild mental retardation. The breakpoints have been microdissected and a small insert library was created. More than 100 sequence tagged sites (STSs) have been developed from these clones for screening of the CEPH mega-YAC library. This work will yield a high density physical map of the breakpoint regions for further characterization of the loci. YACs from the region are being screened by fluorescence in situ hybridization (FISH) to obtain a YAC which crosses the breakpoint as an initial step in defining the molecular basis of the disease phenotype. Progress towards cloning of the breakpoints will be described.

  6. Characterization of a gene from the EDM1-PSACH region of human chromosome 19p

    SciTech Connect

    Lennon, G.G.; Giorgi, D.; Martin, J.R.

    1994-09-01

    Genetic linkage mapping has indicated that both multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia, and pseudoachondroplasia (PSACH), a skeletal disorder associated with dwarfism, map to a 2-3 Mb region of human chromosome 19p. We have isolated a partial cDNA from this region using hybrid selection, and report on progress towards the characterization of the genomic structure and transcription of the corresponding gene. Sequence analysis of the cDNA to date indicates that this gene is likely to be expressed within extracellular matrix tissues. Defects in this gene or neighboring gene family members may therefore lead to EDM1, PSACH, or other connective tissue and skeletal disorders.

  7. Comparative genomic hybridization detects losses of chromosomes 22 and 16 as the most common recurrent genetic alterations in primary ependymomas.

    PubMed

    Zheng, P P; Pang, J C; Hui, A B; Ng, H K

    2000-10-01

    In this study, we used comparative genomic hybridization to provide an overview of chromosomal imbalances in a series of 20 adult and 8 childhood ependymomas. All tumors displayed multiple genomic imbalances. Loss of genetic material was observed in chromosomes 22q (71%), 16 (57%), 17 (46%), 6 (39%), 19q (32%), 20q (32%), and 1p (29%), with the overlapped deletion regions determined at 16p13.1-13.3, 16q22-q24, 19q13.1-13.4, 20q13.1-13.2 and 1p36.1-36.3. Gain of DNA was commonly detected on chromosomes 5q (46%), 12q (39%), 7q (36%), 9q (36%), and 4q (32%), with overlapped regions of gain mapped to 5q21-22, 12q15-24.1, 7q11.2-31.2, 9q12-32, and 4q23-28, respectively. These findings suggest a greater degree of genomic imbalance in ependymomas than has been recognized previously and highlight chromosomal loci likely to contain oncogenes or tumor suppressor genes that may contribute to the molecular pathogenesis of this tumor. Our study also confirmed previous findings on frequent losses of 17 and 22q in ependymomas and further identified chromosome 16 loss as a common recurrent genetic aberration in ependymomas. PMID:11104027

  8. A YAC-, P1, and cosmid-based physical map of the BRCA1 region on chromosome 17q21

    SciTech Connect

    Couch, F.J.; Castilla, L.H.; Brody, L.C.

    1995-01-01

    A familial early-onset breast cancer gene (BRCA1) has been localized to chromosome 17q21. To characterize this region and to aid in the identification of the BRCA1 gene, a physical map of a region of 1.0-1.5 Mb between the EDH17B1 and the PPY loci on chromosome 17q21 was generated. The physical map is composed of a yeast artificial chromosome (YAC) and P1 phage contig with one gap. The majority of the interval has also been converted to a cosmid contig. Twenty-three PCR-based sequence-tagged sites (STSs) were mapped to these contigs, thereby confirming the order and overlap of individual clones. This complex physical map of the BRCA1 region was used to isolate genes by a number of gene identification techniques and to generate transcript maps of the region. 32 refs., 4 figs.

  9. A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12

    SciTech Connect

    Kwon, B.S.; Chintamaneni, C.; Kobayashi, Y.; Kim, K.K. ); Kozak, C.A. ); Copeland, N.G.; Gilbert, D.J.; Jenkins, N. ); Barton, D.; Francke, U. )

    1991-10-15

    Melanocytes preferentially express an mRNA species, Pmel 17, whose protein product cross-reacts with anti-tyrosinase antibodies and whose expression correlates with the melanin content. The authors have now analyzed the deduced protein structure and mapped its chromosomal location in mouse and human. The amino acid sequence deduced from the nucleotide sequence of the Pmel 17 cDNA showed that the protein is composed of 645 amino acids with a molecular weight of 68,600. The Pmel 17 protein contains a putative leader sequence and a potential membrane anchor segment, which indicates that this may be a membrane-associated protein in melanocytes. The deduced protein contains five potential N-glycosylation sites and relatively high levels of serine and threonine. Three repeats of a 26-amino acid motif appear in the middle of the molecule. The human Pmel 17 gene, designated D12S53E, maps to chromosome 12, region 12pter-q21; and the mouse homologue, designated D12S53Eh, maps to the distal region of mouse chromosome 10, a region also known to carry the coat color locus si (silver).

  10. Molecular topography of the secondary constriction region (qh) of human chromosome 9 with an unusual euchromatic band

    SciTech Connect

    Verma, R.S.; Luk, S.; Brennan, J.P.; Mathews, T.; Conte, R.A.; Macera, M.J. )

    1993-05-01

    Heterochromatin confined to pericentromeric (c) and secondary constriction (qh) regions plays a major role in morphological variation of chromosome 9, because of its size and affinity for pericentric inversion. Consequently, pairing at pachytene may lead to some disturbances between homologous chromosomes having such extreme variations and may result in abnormalities involving bands adjacent to the qh region. The authors encountered such a case, where a G-positive band has originated de nova, suggesting a maternal origin from the chromosome 9 that has had a complete pericentric inversion. In previously reported cases, the presence of an extra G-positive band within the 9qh region has been familial, and in the majority of those cases it was not associated with any clinical consequences. Therefore, this anomaly has been referred to as a [open quotes]rare[close quotes] variant. The qh region consists of a mixture of various tandemly repeated DNA sequences, and routine banding techniques have failed to characterize the origin of this extra genetic material. By the chromosome in situ suppression hybridization technique using whole chromosome paint, the probe annealed with the extra G-band, suggesting a euchromatic origin from chromosome 9, presumably band p12. By the fluorescence in situ hybridization technique using alpha- and beta-satellite probes, the dicentric nature was further revealed, supporting the concept of unequal crossing-over during maternal meiosis I, which could account for a duplication of the h region. The G-positive band most likely became genetically inert when it was sandwiched between two blocks of heterochromatin, resulting in a phenotypically normal child. Therefore, an earlier hypothesis, suggesting its origin from heterochromatin through so-called euchromatinization, is refuted here. If the proband's progeny inherit this chromosome, it shall be envisaged as a rare familial variant whose clinical consequences remain obscure. 52 refs., 3 figs.

  11. LINKAGE AND RH MAPPING OF 10 GENES TO A QTL REGION FOR FATNESS AND MUSCLING TRAITS ON PIG CHROMOSOME X

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study 10 genes located on human chromosome region Xq13.1 - Xq24 homologous to a QTL region for fatness and body conformation traits were linkage and RH mapped in the pig. PCR primers for amplification of porcine genomic DNAs were designed from orthologous human or porcine (HTR2C) sequences. ...

  12. Physical localization of eed: A region of mouse chromosome 7 required for gastrulation

    SciTech Connect

    Holdener, B.C.; Thomas, J.W.; Schumacher, A.

    1995-06-10

    In the mouse, the embryonic ectoderm development (eed) region is defined by deletions encompassing the albino (c) locus of chromosome 7. The region is located 1-2 cM distal to the c locus and was of undetermined size. Embryos homozygous for deletions removing eed display defects in axial organization during gastrulation. Two loci, identified by chemical mutagenesis, are known to map within the eed interval. One, {ell}7Rn5, probably represents the gene required for gastrulation. The second, {ell}7Rn6, is required for survival after birth. fit1, a third locus identified by chemical mutagenesis, maps distal to the eed interval and is also required for survival after birth. A 900-kb YAC contig has been constructed, and deletion breakpoints defining the limits of the regions containing these loci have been localized. Their positions place the eed region within a maximum 150-kb interval at the proximal end of the contig, while fit1 maps to a 360-kb interval within the middle of the contig. Several clusters of rare-cutting restriction sites map within these regions and represent potential locations of candidate genes. 26 refs., 6 figs., 2 tabs.

  13. Effect of inversion polymorphism on the neutral nucleotide variability of linked chromosomal regions in Drosophila.

    PubMed Central

    Navarro, A; Barbadilla, A; Ruiz, A

    2000-01-01

    Recombination is a main factor determining nucleotide variability in different regions of the genome. Chromosomal inversions, which are ubiquitous in the genus Drosophila, are known to reduce and redistribute recombination, and thus their specific effect on nucleotide variation may be of major importance as an explanatory factor for levels of DNA variation. Here, we use the coalescent approach to study this effect. First, we develop analytical expressions to predict nucleotide variability in old inversion polymorphisms that have reached mutation-drift-flux equilibrium. The effects on nucleotide variability of a new arrangement appearing in the population and reaching a stable polymorphism are then studied by computer simulation. We show that inversions modulate nucleotide variability in a complex way. The establishment of an inversion polymorphism involves a partial selective sweep that eliminates part of the variability in the population. This is followed by a slow convergence to the equilibrium values. During this convergence, regions close to the breakpoints exhibit much lower variability than central regions. However, at equilibrium, regions close to the breakpoints have higher levels of variability and differentiation between arrangements than regions in the middle of the inverted segment. The implications of these findings for overall variability levels during the evolution of Drosophila species are discussed. PMID:10835391

  14. Geographic stratification of linkage disequilibrium: a worldwide population study in a region of chromosome 22

    PubMed Central

    2004-01-01

    Recent studies of haplotype diversity in a number of genomic regions have suggested that long stretches of DNA are preserved in the same chromosome, with little evidence of recombination events. The knowledge of the extent and strength of these haplotypes could become a powerful tool for future genetic analysis of complex traits. Different patterns of linkage disequilibrium (LD) have been found when comparing individuals of African and European descent, but there is scarce knowledge about the worldwide population stratification. Thus, the study of haplotype composition and the pattern of LD from a global perspective are relevant for elucidating their geographical stratification, as it may have implications in the future analysis of complex traits. We have typed 12 single nucleotide polymorphisms in a chromosome 22 region--previously described as having high LD levels in European populations -- in 39 different world populations. Haplotype structure has a clear continental structure with marked heterogeneity within some continents (Africa, America). The pattern of LD among neighbouring markers exhibits a strong clustering of all East Asian populations on the one hand and of Western Eurasian populations (including Europe) on the other, revealing only two major LD patterns, but with some very specific outliers due to specific demographic histories. Moreover, it should be taken into account that African populations are highly heterogeneous. The present results support the existence of a wide (but not total) communality in LD patterns in human populations from different continental regions, despite differences in their demographic histories, as population factors seem to be less relevant compared with genomic forces in shaping the patterns of LD. PMID:15606995

  15. Genetic linkage mapping of multiple epiphyseal dysplasia to the pericentromeric region of chromosome 19.

    PubMed Central

    Oehlmann, R.; Summerville, G. P.; Yeh, G.; Weaver, E. J.; Jimenez, S. A.; Knowlton, R. G.

    1994-01-01

    Multiple epiphyseal dysplasia (MED) is an inherited chondrodystrophy that results in deformity of articular surfaces and in subsequent degenerative joint disease. The disease is inherited as an autosomal dominant trait with high penetrance. An MED mutation has been mapped by genetic linkage analysis of DNA polymorphisms in a single large pedigree. Close linkage of MED to 130 tested chromosomal markers was ruled out by discordant inheritance patterns. However, strong evidence for linkage of MED to markers in the pericentromeric region of chromosome 19 was obtained. The most closely linked marker was D19S215, with a maximum LOD score of 6.37 at theta = .05. Multipoint linkage analysis indicated that MED is located between D19S212 and D19S215, a map interval of 1.7 cM. Discovery of the map location of MED in this family will facilitate identification of the mutant gene. The closely linked DNA polymorphisms will also provide the means to determine whether other inherited chondrodystrophies have underlying defects in the same gene. PMID:8279467

  16. Histone H2B mutations in inner region affect ubiquitination, centromere function, silencing and chromosome segregation.

    PubMed

    Maruyama, Takeshi; Nakamura, Takahiro; Hayashi, Takeshi; Yanagida, Mitsuhiro

    2006-06-01

    The reiterated nature of histone genes has hampered genetic approach to dissect the role of histones in chromatin dynamics. We here report isolation of three temperature-sensitive (ts) Schizosaccharomyces pombe strains, containing amino-acid substitutions in the sole histone H2B gene (htb1+). The mutation sites reside in the highly conserved, non-helical residues of H2B, which are implicated in DNA-protein or protein-protein interactions in the nucleosome. In the allele of htb1-72, the substitution (G52D) occurs at the DNA binding loop L1, causing disruption of the gene silencing in heterochromatic regions and lagging chromosomes in anaphase. In another allele htb1-223 (P102L) locating in the junction between alpha3 and alphaC, the mutant residue is in contact with H2A and other histones, leading to structural aberrations in the central centromere chromatin and unequal chromosome segregation in anaphase. The third allele htb1-442 (E34K) near alpha1 displayed little defect. Evidence is provided that monoubiquitinated H2B is greatly unstable in P102L mutant, possibly owing to proteasome-independent destruction or enhanced deubiquitination. Histone H2B thus plays an important role in centromere/kinetochore formation. PMID:16688222

  17. Association between simple sequence repeat-rich chromosome regions and intergenomic translocation breakpoints in natural populations of allopolyploid wild wheats

    PubMed Central

    Molnár, István; Cifuentes, Marta; Schneider, Annamária; Benavente, Elena; Molnár-Láng, Márta

    2011-01-01

    Background and Aims Repetitive DNA sequences are thought to be involved in the formation of chromosomal rearrangements. The aim of this study was to analyse the distribution of microsatellite clusters in Aegilops biuncialis and Aegilops geniculata, and its relationship with the intergenomic translocations in these allotetraploid species, wild genetic resources for wheat improvement. Methods The chromosomal localization of (ACG)n and (GAA)n microsatellite sequences in Ae. biuncialis and Ae. geniculata and in their diploid progenitors Aegilops comosa and Aegilops umbellulata was investigated by sequential in situ hybridization with simple sequence repeat (SSR) probes and repeated DNA probes (pSc119·2, Afa family and pTa71) and by dual-colour genomic in situ hybridization (GISH). Thirty-two Ae. biuncialis and 19 Ae. geniculata accessions were screened by GISH for intergenomic translocations, which were further characterized by fluorescence in situ hybridization and GISH. Key Results Single pericentromeric (ACG)n signals were localized on most U and on some M genome chromosomes, whereas strong pericentromeric and several intercalary and telomeric (GAA)n sites were observed on the Aegilops chromosomes. Three Ae. biuncialis accessions carried 7Ub–7Mb reciprocal translocations and one had a 7Ub–1Mb rearrangement, while two Ae. geniculata accessions carried 7Ug–1Mg or 5Ug–5Mg translocations. Conspicuous (ACG)n and/or (GAA)n clusters were located near the translocation breakpoints in eight of the ten translocated chromosomes analysed, SSR bands and breakpoints being statistically located at the same chromosomal site in six of them. Conclusions Intergenomic translocation breakpoints are frequently mapped to SSR-rich chromosomal regions in the allopolyploid species examined, suggesting that microsatellite repeated DNA sequences might facilitate the formation of those chromosomal rearrangements. The (ACG)n and (GAA)n SSR motifs serve as additional chromosome markers

  18. Investigation of the Chromosome Regions with Significant Affinity for the Nuclear Envelope in Fruit Fly – A Model Based Approach

    PubMed Central

    Kinney, Nicholas Allen; Sharakhov, Igor V.; Onufriev, Alexey V.

    2014-01-01

    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 appear to

  19. Variability in the heterochromatin regions of the chromosomes and chromosomal anomalies in children with autism: identification of genetic markers of autistic spectrum disorders.

    PubMed

    Vorsanova, S G; Yurov, I Yu; Demidova, I A; Voinova-Ulas, V Yu; Kravets, V S; Solov'ev, I V; Gorbachevskaya, N L; Yurov, Yu B

    2007-07-01

    Cytogenetic and molecular cytogenetic analysis of children with autism (90 subjects) and their mothers (18 subjects) is presented. Anomalies and fragility were found in chromosome X in four cases of autism: mos 47,XXX[98]/46, XX[2]; 46,XY,r(22)(p11q13); 46,XY,inv(2)(p11.2q13),16qh-; and 46,Y,fra(X)(q27.3),16qh-. C staining and quantitative fluorescent in situ hybridization (FISH) were used to demonstrate a significant increase in the frequency of variations in the heterochromatin regions of chromosomes in children with autism as compared with a control group (48% and 16% respectively). Pericentric chromosome inversion 9phqh was not characteristic of patients with autism, while variation in heterochromatin regions 1phqh, 9qh+, and 16qh-were found significantly more frequently in children with autism. These data provide the basis for discussing the possible role of the gene position effect in the pathogenesis of autism and the possible search for biological markers of autistic disorders. PMID:17657425

  20. Identification of the full-length KIAA0591 gene encoding a novel kinesin-related protein which is mapped to the neuroblastoma suppressor gene locus at 1p36.2.

    PubMed

    Nagai, M; Ichimiya, S; Ozaki, T; Seki, N; Mihara, M; Furuta, S; Ohira, M; Tomioka, N; Nomura, N; Sakiyama, S; Kubo, O; Takakura, K; Hori, T; Nakagawara, A

    2000-05-01

    The distal region of a short arm of chromosome 1p is frequently deleted in many human cancers including neuroblastoma (NBL), in which it has been narrowed down to the smallest region of overlap between D1S244 and D1S214 (approximately 7 cM). During the search for the candidate tumor suppressor genes mapped within the region, we found the KIAA0591 gene which encoded a new human kinesin-related protein with a homology to human axonal transporter of synaptic vesicles (ATSV). The kinesin is an intracellular motor protein and often associated with neuronal differentiation and survival. Here we identified a complete open reading frame of the KIAA0591 gene by screening a cDNA library derived from human substantia nigra. The KIAA0591 protein contains a possible pleckstrin homology (PH) domain at its carboxy-terminus. However, it did not possess a force-generating motor domain which is well conserved among kinesin superfamily members (KIFs). Northern blot analysis demonstrated that KIAA0591 mRNA was preferentially expressed in both adult and fetal brains, kidney, skeletal muscle and pancreas. KIAA0591 was expressed in favorable NBLs at higher levels than in unfavorable NBLs, although RT-PCR SSCP analysis showed no mutation within the coding region of the KIAA0591 gene, when 8 neuroblastoma tissues and 15 neuroblastoma-derived cell lines were examined. Thus, the full-length KIAA0591 gene may be a novel member of human KIF superfamily which lacks motor domain and might function as a tumor suppressor in an epigenetic but not a classic Knudson's manner. PMID:10762626

  1. Population data of Y-chromosomal STRs in Russian males of the Primorye region population.

    PubMed

    Lessig, Rüdiger; Edelmann, Jeanett; Kleemann, Werner J; Kozhemyako, Valeri

    2006-05-25

    Data of eight Y-chromosomal STRs, the so called "minimal core set", were obtained from 152 unrelated males of the Primorye region of Russia. The allelic frequencies correspond to other European populations. The background is a settlement of males from the European part of Russia, Ukraine and other states which were included in the former western part of the Soviet Union. On the other hand the distribution of the most frequent haplotypes differs to the Ukraine and Russian population. The most frequent haplotype was obtained five times in the population corresponding to 3.3%. The haplotype data reported here have been included into the Y-STR database maintained at the Institute of Legal Medicine, Humboldt-University, Berlin. PMID:15964730

  2. Evolution of the vertebrate genome as reflected in paralogous chromosomal regions in man and the house mouse

    SciTech Connect

    Lundin, L.G. )

    1993-04-01

    Gene constellations on several human chromosomes are interpreted as indications of large regional duplications that took place during evolution of the vertebrate genome. Four groups of paralogous chromosomal regions in man and the house mouse are suggested and are believed to be conserved remnants of the two or three rounds of tetraploidization that are likely to have occurred during evolution of the vertebrates. The phenomenon of differential silencing of genes is described. The importance of conservation of linkage of particular genes is discussed in relation to genetic regulation and cell differentiation. 120 refs., 5 tabs.

  3. Localisation of the gene for achondroplasia to the telomeric region of chromosome 4p

    SciTech Connect

    Stoilov, I.; Velinov, M.; Kilpatrick, M.W.

    1994-09-01

    Achondroplasia (ACH), the most common type of genetic dwarfism, is characterized by a variety of skeletal anomalies including disproportionate short stature and rhizomelic shortening of the extremities. The disorder is inherited as an autosomal dominant trait, with a prevalence of 1-15 per 100,000 live births. The etiology of ACH remains unknown, although evidence points to a defect in the maturation of the chondrocytes in the growth plate of the cartilage. To determine the location of the gene responsible for ACH, a panel of 14 families with a total of 43 meioses was genotyped for 40 polymorphic markers for loci randomly distributed throughout the genome. The first significant positive Lod score was obtained for the locus D4S127 (Zmax=3.65 at {theta}=0.03). A series of 20 markers for chromosome 4p16.3 loci were then used to determine the most likely position of the ACH gene. Two additional loci, D4S412 and IDUA, showed strong linkage to the disease (Zmax=3.34 at {theta}=0.03 and Zmax=3.35 at {theta}=0.0, respectively). Multipoint analysis and direct counting of recombinants places the ACH gene in a 2.5 cM region between the marker D4S43 and the chromosome 4p telomere. No evidence was found for genetic heterogeneity. The ACH region contains a number of genes, including that for the fibroblast growth factor receptor FGFR3, which are being evaluated as candidates for the ACH gene. This identification of tightly linked polymorphic markers, as well as being the first step in the characterization of the ACH gene, offers the possibility of DNA based prenatal diagnosis of this disorder.

  4. Pseudoxanthoma elasticum maps to an 820-kb region of the p13.1 region of chromosome 16.

    PubMed

    Le Saux, O; Urban, Z; Göring, H H; Csiszar, K; Pope, F M; Richards, A; Pasquali-Ronchetti, I; Terry, S; Bercovitch, L; Lebwohl, M G; Breuning, M; van den Berg, P; Kornet, L; Doggett, N; Ott, J; de Jong, P T; Bergen, A A; Boyd, C D

    1999-11-15

    We have performed linkage analysis on 21 families with pseudoxanthoma elasticum (PXE) using 10 polymorphic markers located on chromosome 16p13.1. The gene responsible for the PXE phenotype was localized to an 8-cM region of 16p13.1 between markers D16S500 and D16S3041 with a maximum lod score of 8.1 at a recombination fraction of 0.04 for marker D16S3017. The lack of any locus heterogeneity suggests that the major predisposing allele for the PXE phenotype is located in this region. Haplotype studies of a total of 36 PXE families identified several recombinations that further confined the PXE gene to a region (< 1 cM) between markers D16S3060 and D16S79. This PXE locus was identified within a single YAC clone and several overlapping BAC recombinants. From sequence analysis of these BAC recombinants, it is clear that the distance between markers D16S3060 and D16S79 is about 820 kb and contains a total of nine genes including three pseudogenes. We predict that mutations in one of the expressed genes in the locus will be responsible for the PXE phenotype in these families. PMID:10585762

  5. Isolation and characterization of 21 novel expressed DNA sequences from the distal region of human chromosome 4p

    SciTech Connect

    Ishida, Yoshikazu; Hadano, Shinji; Nagayama, Tomiko

    1994-07-15

    The authors have established an approach to the isolation of expressed DNA sequences from a defined region of the human chromosome. The method relies on the direct screening of cDNA libraries using pooled single-copy microclones generated by a laser chromosome microdissection in conjunction with a single unique primer polymerase chain reaction (SUP-PCR) procedure. They applied this method to the distal region of human chromosome 4p (4p15-4pter), which contains the Huntington disease (HD) and the Wolf-Hirschhorn syndrome (WHS) loci. Twenty-one nonoverlapping and region-specific cDNA clones encoding novel genes were isolated in this manner. Ten of 21 clones were subregionally assigned to 4p16.1-4pter, and the remainder mapped to the region proximal to 4p16.1. Northern blot and reverse transcription followed by the PCR (RT-PCR) analysis revealed that 16 of these 21 clones detected transcripts in total RNA from human tissues. The method is applicable to other chromosomal regions and is a powerful approach to the isolation of region-specific cDNA clones. 44 refs., 3 figs., 3 tabs.

  6. Identification and cloning in yeast artificial chromosomes of a region of elevated loss of heterozygosity on chromosome 1p31.1 in human breast cancer

    SciTech Connect

    Hoggard, N.; Hey, Y.; Brintnell, B.; James, L.

    1995-11-20

    We have mapped a region of high loss of heterozygosity in breast cancer to a 2-cM interval between the loci D1S430 and D1S465 on chromosome 1p31.1. This region shows allelic imbalance in around 60% of breast tumors. As part of a strategy to clone the target gene(s) within this interval, we have generated a yeast artificial chromosome contig spanning over 7 Mb. YACs from the CEPH and Zeneca (formerly ICI) libraries have been obtained by screening with PCR-based STSs from the region for both previously identified loci and newly isolated STSs. The YACs have been assembled into a contig by a combination of approaches, including analysis of their STS content, generation of new STSs from the ends of key YACs, and long-range restriction mapping. These YAC clones provide the basis for complete characterization of the region of high loss in breast cancer and for the ultimate identification of the target gene(s). 84 refs., 3 figs., 3 tabs.

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

    SciTech Connect

    McCorquodale, D.J.; McCorquodale, M.; Bereziouk, O.

    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.

  8. Yeast artificial chromosome cloning in the glycerol kinase and adrenal hypoplasia congenita region of Xp21

    SciTech Connect

    Worley, K.C.; Ellison, K.A.; Zhang, Y.H.; Wang, D.F.; Mason, J.; Roth, E.J.; Adams, V.; Fogt, D.D.; Zhu, X.M.; Towbin, J.A.

    1993-05-01

    The adrenal hypoplasia congenita (AHC) and glycerol kinase (GK) loci are telomeric to the Duchenne muscular dystrophy locus in Xp21. The authors developed a pair of yeast artificial chromosome (YAC) contigs spanning at least 1.2 Mb and encompassing the region from the telomeric end of the Duchenne muscular dystrophy (DMD) locus to beyond YHX39 (DXS727), including the genes for AHC and GK. The centromeric contig consists of 13 YACs reaching more than 600 kb from DMD through GK. The telomeric contig group consists of 8 YACs containing more than 600 kb including the markers YHX39 (DXS727) and QST-59 (DXS319). Patient deletion breakpoints in the region of the two YAC contigs define at least eight intervals, and seven deletion breakpoints are contained within these contigs. In addition to the probes developed from YAC ends, they have mapped eight Alu-PCR probes amplified from a radiation-reduced somatic cell hybrid, two anonymous DNA probes, and one Alu-PCR product amplified from a cosmid end, for a total of 26 new markers within this region of 2 Mb or less. One YAC in the centromeric contig contains an insert encompassing the minimum interval for GK deficiency defined by patient deletion breakpoints, and this clone includes all or part of the GK gene. 33 refs., 3 figs., 5 tabs.

  9. The MaoP/maoS Site-Specific System Organizes the Ori Region of the E. coli Chromosome into a Macrodomain.

    PubMed

    Valens, Michèle; Thiel, Axel; Boccard, Frédéric

    2016-09-01

    The Ori region of bacterial genomes is segregated early in the replication cycle of bacterial chromosomes. Consequently, Ori region positioning plays a pivotal role in chromosome dynamics. The Ori region of the E. coli chromosome is organized as a macrodomain with specific properties concerning DNA mobility, segregation of loci and long distance DNA interactions. Here, by using strains with chromosome rearrangements and DNA mobility as a read-out, we have identified the MaoP/maoS system responsible for constraining DNA mobility in the Ori region and limiting long distance DNA interactions with other regions of the chromosome. MaoP belongs to a group of proteins conserved in the Enterobacteria that coevolved with Dam methylase including SeqA, MukBEF and MatP that are all involved in the control of chromosome conformation and segregation. Analysis of DNA rings excised from the chromosome demonstrated that the single maoS site is required in cis on the chromosome to exert its effect while MaoP can act both in cis and in trans. The position of markers in the Ori region was affected by inactivating maoP. However, the MaoP/maoS system was not sufficient for positioning the Ori region at the ¼-¾ regions of the cell. We also demonstrate that the replication and the resulting expansion of bulk DNA are localized centrally in the cell. Implications of these results for chromosome positioning and segregation in E. coli are discussed. PMID:27627105

  10. Genetic linkage studies in familial partial epilepsy: Exclusion of the human chromosome regions syntenic to the El-1 mouse locus

    SciTech Connect

    Lopes-Cendes, I.; Mulley, J.C.; Andermann, E.

    1994-09-01

    Recently, six families with a familial form of partial epilepsy were described. All pedigrees showed autosomal dominant inheritance with incomplete penetrance. Affected individuals present with predominantly nocturnal seizures with frontal lobe semiology. In 1959, a genetic mouse model for partial epilepsy, the El mouse, was reported. In the El mouse, a major seizure susceptibility gene, El-1, segregates in an autosomal dominant fashion and has been localized to a region distal to the centromere of mouse chromosome 9. Comparative genetic maps between man and mouse have been used for prediction of localization of several human disease genes. Because the region of mouse chromosome 9 that is the most likely to contain the El-1 locus is syntenic to regions on human chromosomes 3q21-p22, 3q21-q23.3, 6q12 and 15q24, we adopted the candidate gene approach as an initial linkage strategy. Twenty-two polymorphic microsatellite markers covering these regions were used for genotyping individuals in the three larger families ascertained, two of which are Australian and one French-Canadian. Negative two-point lod scores were obtained separately for each family. The analysis of all three families combined significantly excludes the candidate regions on chromosomes 3, 6 and 15.

  11. Chromosomal Flexibility

    ERIC Educational Resources Information Center

    Journal of College Science Teaching, 2005

    2005-01-01

    Scientists have shown that a genetic element on one chromosome may direct gene activity on another. Howard Hughes Medical Institute (HHMI) researchers report that a multitasking master-control region appears to over-see both a set of its own genes and a related gene on a nearby chromosome. The findings reinforce the growing importance of location…

  12. Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation

    SciTech Connect

    Burian, D.; Clifton, S.W.; Crabtree, J.

    1995-05-01

    The complete human BCR gene (152j-141 nt) on chromosome 22 and greater than 80% of the human ABL gene (179-512 nt) on chromosome 9 have been sequenced from mapped cosmid and plasmid clones via a shotgun strategy. Because these two chromosomes are translocated with breakpoints within the BCR and ABL genes in Philadelphia chromosome-positive leukemias, knowledge of these sequences also might provide insight into the validity of various theories of chromosomal rearrangements. Comparison of these genes with their cDNA sequences reveal the positions of 23 BCR exons and putative alternative BCR first and second exons, as well as the common ABL exons 2-11, respectively. Additionally, these regions include the alternative ABL first exons 1b and 1a, a new gene 5` to the first ABL exon, and an open reading frame with homology to an EST within the BCR fourth intron. Further analysis reveals an Alu homology of 38.83 and 39.35% for the BCR and ABL genes, respectively, with other repeat elements present to a lesser extent. Four new Philadelphia chromosome translocation breakpoints from chronic myelogenous leukemia patients also were sequenced, and the positions of these and several other previously sequenced breakpoints now have been mapped precisely, although no consistent breakpoint features immediately were apparent. Comparative analysis of genomic sequences encompassing the murine homologues to the human ABL exons 1b and 1a, as well as regions encompassing the ABL exons 2 and 3, reveals that although there is a high degree of homology in their corresponding exons and promoter regions, these two vertebrate species show a striking lack of homology outside these regions. 122 refs., 5 figs., 4 tabs.

  13. P-Element Insertion Alleles of Essential Genes on the Third Chromosome of Drosophila Melanogaster: Correlation of Physical and Cytogenetic Maps in Chromosomal Region 86e-87f

    PubMed Central

    Deak, P.; Omar, M. M.; Saunders, RDC.; Pal, M.; Komonyi, O.; Szidonya, J.; Maroy, P.; Zhang, Y.; Ashburner, M.; Benos, P.; Savakis, C.; Siden-Kiamos, I.; Louis, C.; Bolshakov, V. N.; Kafatos, F. C.; Madueno, E.; Modolell, J.; Glover, D. M.

    1997-01-01

    We have established a collection of 2460 lethal or semi-lethal mutant lines using a procedure thought to insert single P elements into vital genes on the third chromosome of Drosophila melanogaster. More than 1200 randomly selected lines were examined by in situ hybridization and 90% found to contain single insertions at sites that mark 89% of all lettered subdivisions of the Bridges' map. A set of chromosomal deficiencies that collectively uncover ~25% of the euchromatin of chromosome 3 reveal lethal mutations in 468 lines corresponding to 145 complementation groups. We undertook a detailed analysis of the cytogenetic interval 86E-87F and identified 87 P-element-induced mutations falling into 38 complementation groups, 16 of which correspond to previously known genes. Twenty-one of these 38 complementation groups have at least one allele that has a P-element insertion at a position consistent with the cytogenetics of the locus. We have rescued P elements and flanking chromosomal sequences from the 86E-87F region in 35 lines with either lethal or genetically silent P insertions, and used these as probes to identify cosmids and P1 clones from the Drosophila genome projects. This has tied together the physical and genetic maps and has linked 44 previously identified cosmid contigs into seven ``supercontigs'' that span the interval. STS data for sequences flanking one side of the P-element insertions in 49 lines has identified insertions in the αγ element at 87C, two known transposable elements, and the open reading frames of seven putative single copy genes. These correspond to five known genes in this interval, and two genes identified by the homology of their predicted products to known proteins from other organisms. PMID:9409831

  14. Incompatibility Between X Chromosome Factor and Pericentric Heterochromatic Region Causes Lethality in Hybrids Between Drosophila melanogaster and Its Sibling Species

    PubMed Central

    Cattani, M. Victoria; Presgraves, Daven C.

    2012-01-01

    The Dobzhansky–Muller model posits that postzygotic reproductive isolation results from the evolution of incompatible epistatic interactions between species: alleles that function in the genetic background of one species can cause sterility or lethality in the genetic background of another species. Progress in identifying and characterizing factors involved in postzygotic isolation in Drosophila has remained slow, mainly because Drosophila melanogaster, with all of its genetic tools, forms dead or sterile hybrids when crossed to its sister species, D. simulans, D. sechellia, and D. mauritiana. To circumvent this problem, we used chromosome deletions and duplications from D. melanogaster to map two hybrid incompatibility loci in F1 hybrids with its sister species. We mapped a recessive factor to the pericentromeric heterochromatin of the X chromosome in D. simulans and D. mauritiana, which we call heterochromatin hybrid lethal (hhl), which causes lethality in F1 hybrid females with D. melanogaster. As F1 hybrid males hemizygous for a D. mauritiana (or D. simulans) X chromosome are viable, the lethality of deficiency hybrid females implies that a dominant incompatible partner locus exists on the D. melanogaster X. Using small segments of the D. melanogaster X chromosome duplicated onto the Y chromosome, we mapped a dominant factor that causes hybrid lethality to a small 24-gene region of the D. melanogaster X. We provide evidence suggesting that it interacts with hhlmau. The location of hhl is consistent with the emerging theme that hybrid incompatibilities in Drosophila involve heterochromatic regions and factors that interact with the heterochromatin. PMID:22446316

  15. Maternal uniparental meroisodisomy in the LAMB3 region of chromosome 1 results in lethal junctional epidermolysis bullosa.

    PubMed

    Takizawa, Y; Pulkkinen, L; Shimizu, H; Lin, L; Hagiwara, S; Nishikawa, T; Uitto, J

    1998-05-01

    Herlitz junctional epidermolysis bullosa (OMIM#226700) is a lethal, autosomal recessive blistering disorder caused by mutations in one of the three genes LAMA3, LAMB3, or LAMC2, encoding the constitutive polypeptide subunits of laminin 5. In this study, we describe a patient homozygous for a novel nonsense mutation Q936X in exon 19 of LAMB3, which has been mapped to chromosome 1q32. The patient was born with extensive blistering and demonstrated negative immunofluorescence staining for laminin 5, and transmission electron microscopy revealed tissue separation within lamina lucida of the dermal-epidermal junction, diagnostic of Herlitz junctional epidermolysis bullosa. The mother of the proband was found to be a heterozygous carrier for this mutation, whereas the father demonstrated the wild-type LAMB3 allele only. Nonpaternity was excluded by 13 microsatellite markers in six different chromosomes. Genotype analysis using 28 microsatellite markers spanning chromosome 1 revealed that the patient had maternal primary heterodisomy, as well as meroisodisomy within two regions of chromosome 1, one on 1p and the other one on 1q, the latter region containing the maternal LAMB3 mutation. These results suggest that Herlitz junctional epidermolysis bullosa in this patient developed as a result of reduction to homozygosity of the maternal LAMB3 mutation on chromosome 1q32. PMID:9579554

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

    PubMed

    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. PMID:27102236

  17. Identification and regional localization of DNA markers on chromosome 7 for the cloning of the cystic fibrosis gene

    PubMed Central

    Rommens, Johanna M.; Zengerling, Stefanie; Burns, Julie; Melmer, Georg; Kerem, Bat-sheva; Plavsic, Natasa; Zsiga, Martha; Kennedy, Dara; Markiewicz, Danuta; Rozmahel, Richard; Riordan, Jack R.; Buchwald, Manuel; Tsui, Lap-chee

    1988-01-01

    To facilitate mapping of the cystic fibrosis locus (CF) and to isolate the corresponding gene, we have screened a flow-sorted chromosome 7–specific library for additional DNA markers in the 7q31-q32 region. Unique (“single-copy”) DNA segments were selected from the library and used in hybridization analysis with a panel of somatic cell hybrids containing various portions of human chromosome 7 and patient cell lines with deletion of this chromosome. A total of 258 chromosome 7–specific single-copy DNA segments were identified, and most of them localized to subregions. Fifty three of these corresponded to DNA sequences in the 7q31-q32 region. Family and physical mapping studies showed that two of the DNA markers, D7S122 and D7S340, are in close linkage with CF. The data also showed that D7S122 and D7S340 map between MET and D7S8, the two genetic markers known to be on opposite sides of CF. The study thus reaffirms the general strategy in approaching a disease locus on the basis of chromosome location. ImagesFigure 2Figure 5 PMID:2903665

  18. Chromosome region-specific libraries for human genome analysis. Progress report, September 1, 1991--August 31, 1992

    SciTech Connect

    Kao, Fa-Ten

    1992-08-01

    During the grant period progress has been made in the successful demonstration of regional mapping of microclones derived from microdissection libraries; successful demonstration of the feasibility of converting microclones with short inserts into yeast artificial chromosome clones with very large inserts for high resolution physical mapping of the dissected region; Successful demonstration of the usefulness of region-specific microclones to isolate region-specific cDNA clones as candidate genes to facilitate search for the crucial genes underlying genetic diseases assigned to the dissected region; and the successful construction of four region-specific microdissection libraries for human chromosome 2, including 2q35-q37, 2q33-q35, 2p23-p25 and 2p2l-p23. The 2q35-q37 library has been characterized in detail. The characterization of the other three libraries is in progress. These region-specific microdissection libraries and the unique sequence microclones derived from the libraries will be valuable resources for investigators engaged in high resolution physical mapping and isolation of disease-related genes residing in these chromosomal regions.

  19. Inferring the demographic history of Drosophila subobscura from nucleotide variation at regions not affected by chromosomal inversions.

    PubMed

    Pratdesaba, Roser; Segarra, Carmen; Aguadé, Montserrat

    2015-04-01

    Drosophila subobscura presents a rich and complex chromosomal inversion polymorphism. It can thus be considered a model system (i) to study the mechanisms originating inversions and how inversions affect the levels and patterns of variation in the inverted regions and (ii) to study adaptation at both the single-gene and chromosomal inversion levels. It is therefore important to infer its demographic history as previous information indicated that its nucleotide variation is not at mutation-drift equilibrium. For that purpose, we sequenced 16 noncoding regions distributed across those parts of the J chromosome not affected by inversions in the studied population and possibly either by other selective events. The pattern of variation detected in these 16 regions is similar to that previously reported within different chromosomal arrangements, suggesting that the latter results would, thus, mainly reflect recent demographic events rather than the partial selective sweep imposed by the origin and frequency increase of inversions. Among the simple demographic models considered in our Approximate Bayesian Computation analysis of variation at the 16 regions, the model best supported by the data implies a population size expansion soon after the penultimate glacial period. This model constitutes a better null model, and it is therefore an important resource for subsequent studies aiming among others to uncover selective events across the species genome. Our results also highlight the importance of introducing the possibility of multiple hits in the coalescent simulations with an outgroup. PMID:25776124

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

    SciTech Connect

    Kubota, T.; Saitoh, S.; Jinno, Y.; Niikawa, N.; Matsumoto, T.; Narahara, K.; Fukushima, Y.

    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.

  1. Use of sample pooling in a genome-wide association study identifies chromosomal regions affecting incidence of bovine respiratory disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We hypothesize that genome-wide association (GWA) based on high-density SNP arrays can be used to identify chromosomal regions affecting disease incidence using a case/control type approach. However, the large sample size required to map a lowly heritable trait like susceptibility to bovine respirat...

  2. Linkage Block and Recombination Suppression at the Pi-ta locus at the Centromere Region of Rice Chromosome 12

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Pi-ta gene, located near the centromeric region of chromosome 12 is an effective resistance gene to Magnaporthe oryzae that causes rice blast disease. Pi-ta has been incorporated into diverse resistant rice cultivars by classical plant breeding in the southern US and worldwide. Previously, la...

  3. A Chromosomal Region on ECA13 Is Associated with Maxillary Prognathism in Horses

    PubMed Central

    Signer-Hasler, Heidi; Neuditschko, Markus; Koch, Christoph; Froidevaux, Sylvie; Flury, Christine; Burger, Dominik; Leeb, Tosso; Rieder, Stefan

    2014-01-01

    Hereditary variations in head morphology and head malformations are known in many species. The most common variation encountered in horses is maxillary prognathism. Prognathism and brachygnathism are syndromes of the upper and lower jaw, respectively. The resulting malocclusion can negatively affect teeth wear, and is considered a non-desirable trait in breeding programs. We performed a case-control analysis for maxillary prognathism in horses using 96 cases and 763 controls. All horses had been previously genotyped with a commercially available 50 k SNP array. We analyzed the data with a mixed-model considering the genomic relationships in order to account for population stratification. Two SNPs within a region on the distal end of chromosome ECA 13 reached the Bonferroni corrected genome-wide significance level. There is no known prognathism candidate gene located within this region. Therefore, our findings in the horse offer the possibility of identifying a novel gene involved in the complex genetics of prognathism that might also be relevant for humans and other livestock species. PMID:24466169

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

    SciTech Connect

    Blackburn, C.C.; Griffith, J.; Morahan, G.

    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.

  5. A 3 Mb YAC contig in the region of Usher Ib on chromosome 11q

    SciTech Connect

    Kelley, P.M.; Overbeck, L.; Weston, M.

    1994-09-01

    Under syndrome type Ib, a recessive disorder characterized by deafness, retinitis pigmentosa, and vestibular dysfunction has been mapped to chromosome 11q13. A 3 Mb YAC contig has been constructed covering the critical region of Usher Ib and spanning over eight loci: D11S1321, D11S527, D11S533, OMP, D11S906, D11S911, D11S937, and D11S918. This contig was constructed by PCR screening using the above described DNA markers of the CEPH mega YAC library. Additional YACs were identified by data presented in the Genethon physical map. A long-range restriction map has been constructed from both YAC and genomic DNA using STS markers as probes. Cosmid libraries from a subset of YACs have been screened for the location of CpG islands. In addition, potential transcribed regions have been identified by 3{prime} exon trapping of cosmid pools and placed on the YAC physical map.

  6. Refined linkage map of chromosome 5 in the region of the spinal muscular atrophy gene

    SciTech Connect

    Melki, J.; Burlet, P.; Clermont, O.; Pascal, F.; Paul, B.; Abdelhak, S.; Munnich, A. ); Sherrington, R.; Gurling, H. Middlesex School of Medicine, London ); Nakamura, Yusuke ); Weissenbach, J. Genethon, Evry ); Lathrop, M. )

    1993-03-01

    The genetic map in the region of human chromosome 5 that harbors the gene for autosomal recessive forms of spinal muscular atrophy (SMA) has been refined by a multilocus linkage study in 50 SMA-segregating families. Among six markers spanning 8 cM for combined sexes, four were shown to be tightly linked to the SMA locus. Multipoing linkage analysis was used to establish the best estimate of the SMA gene location. The data suggest that the most likely location for the SMA locus is between blocks AFM114ye7 (D5S465)/EF5.15 (D5S125) and MAP-1B/JK53 (D5S112) at a sex-combined genetic distance of 2.4 and 1.7 cM, respectively. Thus the SMA gene lies in the 4-cM region between these two blocks. This information is of primary importance for designing strategies for isolating the SMA gene. 16 refs., 2 figs., 4 tabs.

  7. Microdeletions of chromosomal region 22q11 in patients with congenital conotruncal cardiac defects.

    PubMed Central

    Goldmuntz, E; Driscoll, D; Budarf, M L; Zackai, E H; McDonald-McGinn, D M; Biegel, J A; Emanuel, B S

    1993-01-01

    Congenital conotruncal cardiac defects occur with increased frequency in patients with DiGeorge syndrome (DGS). Previous studies have shown that the majority of patients with DGS or velocardiofacial syndrome (VCFS) have a microdeletion within chromosomal region 22q11. We hypothesised that patients with conotruncal defects who were not diagnosed with DGS or VCFS would also have 22q11 deletions. Seventeen non-syndromic patients with one of three types of conotruncal defects most commonly seen in DGS or VCFS were evaluated for a 22q11 deletion. DNA probes from within the DiGeorge critical region were used. Heterozygosity at a locus was assessed using restriction fragment length polymorphisms. Copy number was determined by dosage analysis using Southern blot analysis of fluorescence in situ hybridisation of metaphase spreads. Five of 17 patients were shown to have a 22q11 deletion when evaluated by dosage analysis. This study shows a genetic contribution to the development of some conotruncal cardiac malformations and alters knowledge regarding the risk of heritability of these defects in certain cases. Images PMID:7901419

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

    PubMed Central

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

    2016-01-01

    Abstract 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 Cot1-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 Cot1-DNA showed that different microsatellites, transposons, retrotransposons, and some gene families also comprise the fraction of repetitive DNA in the teiid species. FISH using Cot1-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, Cot1-DNA probe isolated from Ameiva ameiva had multiple interstitial signals on chromosomes, whereas mapping of Cot1-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. PMID:27551343

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

    PubMed

    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. PMID:27551343

  10. Expansion of the Pseudo-autosomal Region and Ongoing Recombination Suppression in the Silene latifolia Sex Chromosomes

    PubMed Central

    Bergero, Roberta; Qiu, Suo; Forrest, Alan; Borthwick, Helen; Charlesworth, Deborah

    2013-01-01

    There are two very interesting aspects to the evolution of sex chromosomes: what happens after recombination between these chromosome pairs stops and why suppressed recombination evolves. The former question has been intensively studied in a diversity of organisms, but the latter has been studied largely theoretically. To obtain empirical data, we used codominant genic markers in genetic mapping of the dioecious plant Silene latifolia, together with comparative mapping of S. latifolia sex-linked genes in S. vulgaris (a related hermaphrodite species without sex chromosomes). We mapped 29 S. latifolia fully sex-linked genes (including 21 newly discovered from transcriptome sequencing), plus 6 genes in a recombining pseudo-autosomal region (PAR) whose genetic map length is ∼25 cM in both male and female meiosis, suggesting that the PAR may contain many genes. Our comparative mapping shows that most fully sex-linked genes in S. latifolia are located on a single S. vulgaris linkage group and were probably inherited from a single autosome of an ancestor. However, unexpectedly, our maps suggest that the S. latifolia PAR region expanded through translocation events. Some genes in these regions still recombine in S. latifolia, but some genes from both addition events are now fully sex-linked. Recombination suppression is therefore still ongoing in S. latifolia, and multiple recombination suppression events have occurred in a timescale of few million years, much shorter than the timescale of formation of the most recent evolutionary strata of mammal and bird sex chromosomes. PMID:23733786

  11. Hyperexpression of HOXC13, located in the 12q13 chromosomal region, in well-differentiated and dedifferentiated human liposarcomas

    PubMed Central

    CANTILE, MONICA; GALLETTA, FRANCESCA; FRANCO, RENATO; AQUINO, GABRIELLA; SCOGNAMIGLIO, GIOSUÈ; MARRA, LAURA; CERRONE, MARGHERITA; MALZONE, GABRIELLA; MANNA, ANGELA; APICE, GAETANO; FAZIOLI, FLAVIO; BOTTI, GERARDO; DE CHIARA, ANNAROSARIA

    2013-01-01

    Liposarcoma (LPS) is the most common soft tissue neoplasm in adults and is characterized by neoplastic adipocyte proliferation. Some subtypes of LPSs show aberrations involving the chromosome 12. The most frequent are t(12;16) (q13;p11) present in more than 90% of myxoid LPSs and 12q13-15 amplification in well-differentiated and dedifferentiated LPSs. In this region, there are important oncogenes such as CHOP (DDIT3), GLI, MDM2, CDK4, SAS, HMGA2, but also the HOXC locus, involved in development and tumor progression. In this study, we evaluated the expression of HOXC13, included in this chromosomal region, in a series of adipocytic tumors. We included 18 well-differentiated, 4 dedifferentiated, 11 myxoid and 6 pleomorphic LPSs as well as 13 lipomas in a tissue microarray. We evaluated the HOXC13 protein and gene expression by immunohistochemistry and quantitative PCR. Amplification/translocation of the 12q13-15 region was verified by FISH. Immunohistochemical HOXC13 overexpression was observed in all well-differentiated and dedifferentiated LPSs, all characterized by the chromosome 12q13-15 amplification, and confirmed by quantitative PCR analysis. In conclusion, our data show a deregulation of the HOXC13 marker in well-differentiated and dedifferentiated LPSs, possibly related to 12q13-15 chromosomal amplification. PMID:24085196

  12. Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains

    PubMed Central

    Brackley, Chris A.; Johnson, James; Kelly, Steven; Cook, Peter R.; Marenduzzo, Davide

    2016-01-01

    Biophysicists are modeling conformations of interphase chromosomes, often basing the strengths of interactions between segments distant on the genetic map on contact frequencies determined experimentally. Here, instead, we develop a fitting-free, minimal model: bivalent or multivalent red and green ‘transcription factors’ bind to cognate sites in strings of beads (‘chromatin’) to form molecular bridges stabilizing loops. In the absence of additional explicit forces, molecular dynamic simulations reveal that bound factors spontaneously cluster—red with red, green with green, but rarely red with green—to give structures reminiscent of transcription factories. Binding of just two transcription factors (or proteins) to active and inactive regions of human chromosomes yields rosettes, topological domains and contact maps much like those seen experimentally. This emergent ‘bridging-induced attraction’ proves to be a robust, simple and generic force able to organize interphase chromosomes at all scales. PMID:27060145

  13. Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains.

    PubMed

    Brackley, Chris A; Johnson, James; Kelly, Steven; Cook, Peter R; Marenduzzo, Davide

    2016-05-01

    Biophysicists are modeling conformations of interphase chromosomes, often basing the strengths of interactions between segments distant on the genetic map on contact frequencies determined experimentally. Here, instead, we develop a fitting-free, minimal model: bivalent or multivalent red and green 'transcription factors' bind to cognate sites in strings of beads ('chromatin') to form molecular bridges stabilizing loops. In the absence of additional explicit forces, molecular dynamic simulations reveal that bound factors spontaneously cluster-red with red, green with green, but rarely red with green-to give structures reminiscent of transcription factories. Binding of just two transcription factors (or proteins) to active and inactive regions of human chromosomes yields rosettes, topological domains and contact maps much like those seen experimentally. This emergent 'bridging-induced attraction' proves to be a robust, simple and generic force able to organize interphase chromosomes at all scales. PMID:27060145

  14. Male-specific region of the bovine Y chromosome is gene rich with a high transcriptomic activity in testis development.

    PubMed

    Chang, Ti-Cheng; Yang, Yang; Retzel, Ernest F; Liu, Wan-Sheng

    2013-07-23

    The male-specific region of the mammalian Y chromosome (MSY) contains clusters of genes essential for male reproduction. The highly repetitive and degenerative nature of the Y chromosome impedes genomic and transcriptomic characterization. Although the Y chromosome sequence is available for the human, chimpanzee, and macaque, little is known about the annotation and transcriptome of nonprimate MSY. Here, we investigated the transcriptome of the MSY in cattle by direct testis cDNA selection and RNA-seq approaches. The bovine MSY differs radically from the primate Y chromosomes with respect to its structure, gene content, and density. Among the 28 protein-coding genes/families identified on the bovine MSY (12 single- and 16 multicopy genes), 16 are bovid specific. The 1,274 genes identified in this study made the bovine MSY gene density the highest in the genome; in comparison, primate MSYs have only 31-78 genes. Our results, along with the highly transcriptional activities observed from these Y-chromosome genes and 375 additional noncoding RNAs, challenge the widely accepted hypothesis that the MSY is gene poor and transcriptionally inert. The bovine MSY genes are predominantly expressed and are differentially regulated during the testicular development. Synonymous substitution rate analyses of the multicopy MSY genes indicated that two major periods of expansion occurred during the Miocene and Pliocene, contributing to the adaptive radiation of bovids. The massive amplification and vigorous transcription suggest that the MSY serves as a genomic niche regulating male reproduction during bovid expansion. PMID:23842086

  15. Using transcriptome profiling to characterize QTL regions on chicken chromosome 5

    PubMed Central

    2009-01-01

    Background Although many QTL for various traits have been mapped in livestock, location confidence intervals remain wide that makes difficult the identification of causative mutations. The aim of this study was to test the contribution of microarray data to QTL detection in livestock species. Three different but complementary approaches are proposed to improve characterization of a chicken QTL region for abdominal fatness (AF) previously detected on chromosome 5 (GGA5). Results Hepatic transcriptome profiles for 45 offspring of a sire known to be heterozygous for the distal GGA5 AF QTL were obtained using a 20 K chicken oligochip. mRNA levels of 660 genes were correlated with the AF trait. The first approach was to dissect the AF phenotype by identifying animal subgroups according to their 660 transcript profiles. Linkage analysis using some of these subgroups revealed another QTL in the middle of GGA5 and increased the significance of the distal GGA5 AF QTL, thereby refining its localization. The second approach targeted the genes correlated with the AF trait and regulated by the GGA5 AF QTL region. Five of the 660 genes were considered as being controlled either by the AF QTL mutation itself or by a mutation close to it; one having a function related to lipid metabolism (HMGCS1). In addition, a QTL analysis with a multiple trait model combining this 5 gene-set and AF allowed us to refine the QTL region. The third approach was to use these 5 transcriptome profiles to predict the paternal Q versus q AF QTL mutation for each recombinant offspring and then refine the localization of the QTL from 31 cM (100 genes) at a most probable location confidence interval of 7 cM (12 genes) after determining the recombination breakpoints, an interval consistent with the reductions obtained by the two other approaches. Conclusion The results showed the feasibility and efficacy of the three strategies used, the first revealing a QTL undetected using the whole population, the

  16. Over-representation of specific regions of chromosome 22 in cells from human glioma correlate with resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea

    PubMed Central

    Hank, Nicole C; Shapiro, Joan Rankin; Scheck, Adrienne C

    2006-01-01

    Background Glioblastoma multiforme is the most malignant form of brain tumor. Despite treatment including surgical resection, adjuvant chemotherapy, and radiation, these tumors typically recur. The recurrent tumor is often resistant to further therapy with the same agent, suggesting that the surviving cells that repopulate the tumor mass have an intrinsic genetic advantage. We previously demonstrated that cells selected for resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are near-diploid, with over-representation of part or all of chromosomes 7 and 22. While cells from untreated gliomas often have over-representation of chromosome 7, chromosome 22 is typically under-represented. Methods We have analyzed cells from primary and recurrent tumors from the same patient before and after in vitro selection for resistance to clinically relevant doses of BCNU. Karyotypic analyses were done to demonstrate the genetic makeup of these cells, and fluorescent in situ hybridization analyses have defined the region(s) of chromosome 22 retained in these BCNU-resistant cells. Results Karyotypic analyses demonstrated that cells selected for BCNU resistance were near-diploid with over-representation of chromosomes 7 and 22. In cells where whole copies of chromosome 22 were not identified, numerous fragments of this chromosome were retained and inserted into several marker and derivative chromosomes. Fluorescent in situ hybridization analyses using whole chromosome paints confirmed this finding. Additional FISH analysis using bacterial artificial chromosome probes spanning the length of chromosome 22 have allowed us to map the over-represented region to 22q12.3–13.32. Conclusion Cells selected for BCNU resistance either in vivo or in vitro retain sequences mapped to chromosome 22. The specific over-representation of sequences mapped to 22q12.3–13.32 suggest the presence of a DNA sequence important to BCNU survival and/or resistance located in this region of chromosome 22

  17. Mapping strategies: Chromosome 16 workshop

    SciTech Connect

    Not Available

    1989-01-01

    The following topics from a workshop on chromosome 16 are briefly discussed: genetic map of chromosome 16; chromosome breakpoint map of chromosome 16; integrated physical/genetic map of chromosome 16; pulsed field map of the 16p13.2--p13.3 region (3 sheets); and a report of the HGM10 chromosome 16 committee.

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

    PubMed

    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. PMID:24821208

  19. A novel human phosphoglucomutase (PGM5) maps to the centromeric region of chromosome 9

    SciTech Connect

    Edwards, Y.H.; Putt, W.; Fox, M.; Ives, J.H.

    1995-11-20

    The phophoglucomutases (PGM1-3) in humans are surrounded by three genes, PGM1, PGM2, and PGM3. These enzymes are central to carbohydrate metabolism. All three isozymes show genetic variation, and PGM1 has achieved prominence as a key marker in genetic linkage mapping and in forensic science. The human PGM genes are assumed to have arisen by gene duplication since their products are broadly similar in structure and function; however, direct proof of their evolutionary relationship is not available because only PGM1 has been cloned. During a search for other members of the PGM family, a novel sequence with homology to PGM1 was identified. Mapping using fluorescence in situ hybridization and somatic cell hybrids locates this gene to the centromeric region of chromosome 9. RT-PCR and Northern analysis indicate that this is an expressed PGM gene with widespread distribution in adult and fetal tissues. We propose that this gene be designated PGM5 and that it represents a novel member of the PGM family. 19 refs., 2 figs.

  20. Expression, function, and targeting of the nuclear exporter chromosome region maintenance 1 (CRM1) protein

    PubMed Central

    Ishizawa, Jo; Kojima, Kensuke; Hail, Numsen; Tabe, Yoko; Andreeff, Michael

    2015-01-01

    Nucleocytoplasmic trafficking of proteins/RNAs is essential to normal cellular function. Indeed, accumulating evidence suggests that cancer cells escape anti-neoplastic mechanisms and benefit from pro-survival signals via the dysregulation of this system. The nuclear exporter chromosome region maintenance 1 (CRM1) protein is the only protein in the karyopherin-β protein family that contributes to the trafficking of numerous proteins and RNAs from the nucleus. It is considered to be an oncogenic, anti-apoptotic protein in transformed cells, since it reportedly functions as a gatekeeper for cell survival, including affecting p53 function, and ribosomal biogenesis. Furthermore, abnormally high expression of CRM1 is correlated with poor patient prognosis in various malignancies. Therapeutic targeting of CRM1 has emerged as a novel cancer treatment strategy, starting with a clinical trial with leptomycin B, the original specific inhibitor of CRM1, followed by development of several next-generation small molecules. KPT-330, a novel member of the CRM1-selective inhibitors of nuclear export (SINE) class of compounds, is currently undergoing clinical evaluation for the therapy of various malignancies. Results from these trials suggest that SINE compounds may be particularly useful against hematological malignancies, which often become refractory to standard chemotherapeutic agents. PMID:26048327

  1. Organization of the R chromosome region in maize: Report of progress

    SciTech Connect

    Kermicle, J.

    1987-02-01

    The maize R gene exhibits various features of regulated gene expression. Alleles collected from diverse geographic sources govern the presence and distribution of anthocyanin pigmentation, plant part by plant part. Some alleles confer stable patterns of pigmentation, while others confer unstable somatic phenotypes with frequent germinal mutations. A remarkable change in expression occurs when certain alleles are combined as heterozygotes. Efficient analysis of such phenomena requires a basic understanding of allelic organization. R is organized on a modular basis, with polymorphism both for number and kind of unit. An allele may carry one such unit, or two or more associated with duplicated chromosome segments. When multiple, each unit mutates independently, with its variants constituting a single complementation group. Because such units behave as separate genes, they have been referred to as ''genic elements''. Alleles organized as gene complexes often have been utilized in the discovery and initial description of phenomena of R regulation. When this is so, subsequent analysis proceeds in two stages. The complex is first fractionated by recombination into simpler derivatives that manifest the phenomenon. Such derivatives, preferably carrying a single element, are then candidates for detailed analysis. For the present study, insertional mutagenesis using transposable sequences proved the most effective means of producing R variants for fine structure study. It was also necessary to describe the pattern of recombination that prevailed in this region when insertions were present. With the advent of molecular cloning of maize genes by transposon tagging, a more direct means of investigating R structure was envisioned. 12 refs.

  2. Further mapping of an ataxia-telangiectasia locus to the chromosome 11q23 region.

    PubMed Central

    Sanal, O; Wei, S; Foroud, T; Malhotra, U; Concannon, P; Charmley, P; Salser, W; Lange, K; Gatti, R A

    1990-01-01

    We recently mapped the gene for ataxia-telangiectasia group A (ATA) to chromosome 11q22-23 by linkage analysis, using the genetic markers THY1 and pYNB3.12 (D11S144). The most likely order was cent-AT-S144-THY1. The present paper describes further mapping of the AT locus by means of a panel of 10 markers that span approximately 60 cM in the 11q22-23 region centered around S144 and THY1. Location scores indicate that three contiguous subsegments within the [S144-THY1] segment, as well as three contiguous segments telomeric to THY1, are each unlikely to contain the AT locus, while the more centromeric [STMY-S144] segment is most likely to contain the AT locus. These data, together with recent refinements in the linkage and physical maps of 11q22-23, place the AT locus at 11q23. PMID:2220826

  3. Unique chromosomal regions associated with virulence of an avian pathogenic Escherichia coli strain.

    PubMed Central

    Brown, P K; Curtiss, R

    1996-01-01

    The avian pathogenic Escherichia coli strain (chi)7122 (serotype O78:K80:H9) causes airsacculitis and colisepticemia in chickens. To identify genes associated with avian disease, a genomic subtraction technique was performed between strain (chi)7122 and the E. coli K-12 strain (chi)289. The DNA isolated using this method was found only in strain (chi)7122 and was used to identify cosmid clones carrying unique DNA from a library of (chi)7122 that were then used to map the position of unique DNA on the E. coli chromosome. A total of 12 unique regions were found, 5 of which correspond to previously identified positions for unique DNA sequence in E. coli strains. To assess the role each unique region plays in virulence, mutants of (chi)7122 were constructed in which a segment of unique DNA was replaced with E. coli K-12 DNA by cotransduction of linked transposon insertions in DNA flanking the unique sequence. The resulting replacement mutants were assessed for inability to colonize the air sac and cause septicemia in 2-week-old white Leghorn chickens. Two mutants were found to be avirulent when injected into the right caudal air sac of 2-week-old chickens. One avirulent mutant, designated (chi)7145, carries a replacement of the rfb locus at 44 min, generating a rough phenotype. The second mutant is designated (chi)7146, and carries a replacement at position 0.0 min on the genetic map. Both mutants could be complemented to partial virulence by cosmids carrying sequences unique to (chi)7122. Images Fig. 1 Fig. 3 PMID:8855324

  4. Data-driven insights into deletions of Mycobacterium tuberculosis complex chromosomal DR region using spoligoforests.

    PubMed

    Ozcaglar, Cagri; Shabbeer, Amina; Kurepina, Natalia; Yener, Bülent; Bennett, Kristin P

    2011-01-01

    Biomarkers of Mycobacterium tuberculosis complex (MTBC) mutate over time. Among the biomarkers of MTBC, spacer oligonucleotide type (spoligotype) and Mycobacterium Interspersed Repetitive Unit (MIRU) patterns are commonly used to genotype clinical MTBC strains. In this study, we present an evolution model of spoligotype rearrangements using MIRU patterns to disambiguate the ancestors of spoligotypes, in a large patient dataset from the United States Centers for Disease Control and Prevention (CDC). Based on the contiguous deletion assumption and rare observation of convergent evolution, we first generate the most parsimonious forest of spoligotypes, called a spoligoforest, using three genetic distance measures. An analysis of topological attributes of the spoligoforest and number of variations at the direct repeat (DR) locus of each strain reveals interesting properties of deletions in the DR region. First, we compare our mutation model to existing mutation models of spoligotypes and find that our mutation model produces as many within-lineage mutation events as other models, with slightly higher segregation accuracy. Second, based on our mutation model, the number of descendant spoligotypes follows a power law distribution. Third, contrary to prior studies, the power law distribution does not plausibly fit to the mutation length frequency. Finally, the total number of mutation events at consecutive DR loci follows a bimodal distribution, which results in accumulation of shorter deletions in the DR region. The two modes are spacers 13 and 40, which are hotspots for chromosomal rearrangements. The change point in the bimodal distribution is spacer 34, which is absent in most MTBC strains. This bimodal separation results in accumulation of shorter deletions, which explains why a power law distribution is not a plausible fit to the mutation length frequency. PMID:22343484

  5. Identification and high-density mapping of gene-rich regions in chromosome group 1 of wheat.

    PubMed

    Gill, K S; Gill, B S; Endo, T R; Taylor, T

    1996-12-01

    We studied the distribution of genes and recombination in wheat (Triticum aestivum) group 1 chromosomes by comparing high-density physical and genetic maps. Physical maps of chromosomes 1A, 1B, and 1D were generated by mapping 50 DNA markers on 56 single-break deletion lines. A consensus physical map was compared with the 1D genetic map of Triticum tauschii (68 markers) and a Triticeae group 1 consensus map (288 markers) to generate a cytogenetic ladder map (CLM). Most group 1 markers (86%) were present in five clusters that encompassed only 10% of the group 1 chromosome. This distribution may reflect that of genes because more than half of the probes were cDNA clones and 30% were PstI genomic. All 14 agronomically important genes in group 1 chromosomes were present in these clusters. Most recombination occurred in gene-cluster regions. Markers fell at an average distance of 244 kb in these regions. The CLM involving the Triticeae consensus genetic map revealed that the above distribution of genes and recombination is the same in other Triticeae species. Because of a significant number of common markers, our CLM can be used for comparative mapping and to estimate physical distances among markers in many Poaceae species including rice and maize. PMID:8978071

  6. Mechanism of fragility at BCL2 gene minor breakpoint cluster region during t(14;18) chromosomal translocation.

    PubMed

    Nambiar, Mridula; Raghavan, Sathees C

    2012-03-16

    The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Breaks in chromosome 18 are localized at the 3'-UTR of BCL2 gene or downstream and are mainly clustered in either the major breakpoint region or the minor breakpoint cluster region (mcr). The recombination activating gene (RAG) complex induces breaks at IgH locus of chromosome 14, whereas the mechanism of fragility at BCL2 mcr remains unclear. Here, for the first time, we show that RAGs can nick mcr; however, the mechanism is unique. Three independent nicks of equal efficiency are generated, when both Mg(2+) and Mn(2+) are present, unlike a single nick during V(D)J recombination. Further, we demonstrate that RAG binding and nicking at the mcr are independent of nonamer, whereas a CCACCTCT motif plays a critical role in its fragility, as shown by sequential mutagenesis. More importantly, we recapitulate the BCL2 mcr translocation and find that mcr can undergo synapsis with a standard recombination signal sequence within the cells, in a RAG-dependent manner. Further, mutation to the CCACCTCT motif abolishes recombination within the cells, indicating its vital role. Hence, our data suggest a novel, physiologically relevant, nonamer-independent mechanism of RAG nicking at mcr, which may be important for generation of chromosomal translocations in humans. PMID:22275374

  7. Chromosomal abnormalities in mentally retarded children in the Konya region--Turkey.

    PubMed

    Cora, T; Demirel, S; Acar, A

    2000-01-01

    Etiology of mental retardation is diverse. 120 Students from 11 special training, education, and rehabilitation subclasses were investigated cytogenetically for determining the contribution of chromosomal abnormalities to mild mental retardation. 23 of the 120 children (19%) had chromosomal abnormalities: thirteen cases a classical trisomy 21 (the male:female ratio was 9:4), three a balanced autosomal reciprocal translocation, one a pericentric inversion of chromosome 9, and six fragile-X syndrome (The male:female ratio was 5:1). PMID:10756429

  8. Y-Chromosomal Lineages of Latvians in the Context of the Genetic Variation of the Eastern-Baltic Region.

    PubMed

    Pliss, Liana; Timša, Līga; Rootsi, Siiri; Tambets, Kristiina; Pelnena, Inese; Zole, Egija; Puzuka, Agrita; Sabule, Areta; Rozane, Sandra; Lace, Baiba; Kucinskas, Vaidutis; Krumina, Astrida; Ranka, Renate; Baumanis, Viesturs

    2015-11-01

    Variations of the nonrecombining Y-chromosomal region were investigated in 159 unrelated Baltic-speaking ethnic Latvians from four different geographic regions, using 28 biallelic markers and 12 short tandem repeats. Eleven different haplogroups (hgs) were detected in a regionally homogeneous Latvian population, among which N1c, R1a, and I1 cover more than 85% of its paternal lineages. When compared its closest geographic neighbors, the composition of the Latvian Y-chromosomal gene pool was found to be very similar to those of Lithuanians and Estonians. Despite the comparable frequency distribution of hg N1c in Latvians and Lithuanians with the Finno-Ugric-speaking populations from the Eastern coast of the Baltic Sea, the observed differences in allelic variances of N1c haplotypes between these two groups are in concordance with the previously stated hypothesis of different dispersal ways of this lineage in the region. More than a third of Latvian paternal lineages belong specifically to a recently defined R1a-M558 hg, indicating an influence from a common source within Eastern Slavic populations on the formation of the present-day Latvian Y-chromosome gene pool. PMID:26411886

  9. A large, dominant pedigree of atrioventricular septal defect (AVSD): Exclusion from the Down syndrome critical region on chromosome 21

    SciTech Connect

    Wilson, L.; Curtis, A.; Stephenson, A.; Goodship, J.; Burn, J. ); Korenberg, J.R.; Schipper, R.D. ); Allan, L. ); Chenevix-Trench, G. )

    1993-12-01

    The authors describe a large pedigree of individuals with autosomal dominant atrioventricular septal defect (AVSD). The pedigree includes affected individuals and individuals who have transmitted the defect but are not clinically affected. AVSDs are a rare congenital heart malformation that occurs as only 2.8% of isolated cardiac lesions. They are the predominant heart defect in children with Down syndrome, making chromosome 21 a candidate for genes involved in atrioventricular septal development. The authors have carried out a linkage study in the pedigree by using 10 simple-sequence polymorphisms from chromosome 21. Multipoint linkage analysis gives lod scores of less than [minus]2 for the region of trisomy 21 associated with heart defects, which excludes a locus within this region as the cause of the defect in this family. 34 refs., 5 figs.

  10. A large, dominant pedigree of atrioventricular septal defect (AVSD): exclusion from the Down syndrome critical region on chromosome 21.

    PubMed Central

    Wilson, L; Curtis, A; Korenberg, J R; Schipper, R D; Allan, L; Chenevix-Trench, G; Stephenson, A; Goodship, J; Burn, J

    1993-01-01

    We describe a large pedigree of individuals with autosomal dominant atrioventricular septal defect (AVSD). The pedigree includes affected individuals and individuals who have transmitted the defect but are not clinically affected. AVSDs are a rare congenital heart malformation that occurs as only 2.8% of isolated cardiac lesions. They are the predominant heart defect in children with Down syndrome, making chromosome 21 a candidate for genes involved in atrioventricular septal development. We have carried out a linkage study in the pedigree by using 10 simple-sequence polymorphisms from chromosome 21. Multipoint linkage analysis gives lod scores of less than -2 for the region of trisomy 21 associated with heart defects, which excludes a locus within this region as the cause of the defect in this family. Images Figure 3 PMID:8250042

  11. Chromosomal microarray testing identifies a 4p terminal region associated with seizures in Wolf–Hirschhorn syndrome

    PubMed Central

    South, Sarah T; Lortz, Amanda; Hensel, Charles H; Sdano, Mallory R; Vanzo, Rena J; Martin, Megan M; Peiffer, Andreas; Lambert, Christophe G; Calhoun, Amy; Carey, John C; Battaglia, Agatino

    2016-01-01

    Background Wolf–Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving variable size deletions of the 4p16.3 region. Seizures are frequently, but not always, associated with WHS. We hypothesised that the size and location of the deleted region may correlate with seizure presentation. Methods Using chromosomal microarray analysis, we finely mapped the breakpoints of copy number variants (CNVs) in 48 individuals with WHS. Seizure phenotype data were collected through parent-reported answers to a comprehensive questionnaire and supplemented with available medical records. Results We observed a significant correlation between the presence of an interstitial 4p deletion and lack of a seizure phenotype (Fisher's exact test p=3.59e-6). In our cohort, there were five individuals with interstitial deletions with a distal breakpoint at least 751 kbp proximal to the 4p terminus. Four of these individuals have never had an observable seizure, and the fifth individual had a single febrile seizure at the age of 1.5 years. All other individuals in our cohort whose deletions encompass the terminal 751 kbp region report having seizures typical of WHS. Additional examples from the literature corroborate these observations and further refine the candidate seizure susceptibility region to a region 197 kbp in size, starting 368 kbp from the terminus of chromosome 4. Conclusions We identify a small terminal region of chromosome 4p that represents a seizure susceptibility region. Deletion of this region in the context of WHS is sufficient for seizure occurrence. PMID:26747863

  12. Ethylnitrosourea Mutagenesis and the Isolation of Mutant Alleles for Specific Genes Located in the t Region of Mouse Chromosome 17

    PubMed Central

    Bode, Vernon C.

    1984-01-01

    Ethylnitrosourea mutagenesis of spermatogonia in male mice is very efficient and makes it practical to isolate new desired mutant alleles by subsequent progeny screening. This is demonstrated for three genes in the t region of chromosome 17. The first, a mutation designated t-int, interacts with the dominant mutation, T (Brachyury), to produce a tailless mouse. Previously, mutant alleles of the t-int gene were available only in t haplotypes, where they are part of a t chromatin block within which recombination with wild-type chromosomes is inhibited. In addition to t-int, new mutations at the quaking and tufted loci were obtained, as well as at several loci not on chromosome 17, e.g., an X-linked lethal that causes a mottled phenotype in the heterozygote and four new mutant W alleles on chromosome 5. In the experiment, an average of one fertilizing spermatozoan in 1500 was mutant at a given locus and an average of one male in five was able to sire mutants at that locus. PMID:6500258

  13. A Genetic and Molecular Analysis of the 46c Chromosomal Region Surrounding the Fmrfamide Neuropeptide Gene in Drosophila Melanogaster

    PubMed Central

    O'Brien, M. A.; Roberts, M. S.; Taghert, P. H.

    1994-01-01

    We have analyzed the FMRFamide neuropeptide gene region of Drosophila melanogaster. This gene maps to the 46C region of chromosome 2R; this interval previously was not well characterized. For this genetic and molecular analysis, we have used X-ray mutagenesis, EMS mutagenesis, and the recently reported local P element transposition method. We identified four overlapping deletions, two of which have proximal breakpoints that define a 50-60-kb region surrounding the FMRFamide gene in 46C. To this small region, we mapped three lethal complementation groups; 10 additional lethal complementation groups were mapped to more distal regions of 46CD. One of these groups corresponds to even-skipped, the other 12 are previously unidentified. Using various lines of evidence we excluded the possibility that FMRFamide corresponds to any of the three lethal complementation groups mapping to its immediate 50-60-kb vicinity. The positions of two of the three lethal complementation groups were identified with P elements using a local transposition scheme. The third lethal complementation group was excluded as being FMRFamide mutants by sequence analysis and by immunocytochemistry with proFMRFamide precursor-specific antibodies. This analysis has (1) provided a genetic map of the 46CD chromosomal region and a detailed molecular map of a portion of the 46C region and (2) provided additional evidence of the utility of local transposition for targeting nearby genes. PMID:8056304

  14. Comparative genetic mapping between duplicated segments on maize chromosomes 3 and 8 and homoeologous regions in sorghum and sugarcane.

    PubMed

    Dufour, P; Grivet, L; D'Hont, A; Deu, M; Trouche, G; Glaszmann, J C; Hamon, P

    1996-06-01

    Comparative mapping within maize, sorghum and sugarcane has previously revealed the existence of syntenic regions between the crops. In the present study, mapping on the sorghum genome of a set of probes previously located on the maize and sugarcane maps allow a detailed analysis of the relationship between maize chromosomes 3 and 8 and sorghum and sugarcane homoeologous regions. Of 49 loci revealed by 46 (4 sugarcane and 42 maize) polymorphic probes in sorghum, 42 were linked and were assigned to linkage groups G (28), E (10) and I (4). On the basis of common probes, a complete co-linearity is observed between sorghum linkage group G and the two sugarcane linkage groups II and III. The comparison between the consensus sorghum/sugarcane map (G/II/III) and the maps of maize chromosomes 3 and 8 reveals a series of linkage blocks within which gene orders are conserved. These blocks are interspersed with non-homoeologous regions corresponding to the central part of the two maize chromosomes and have been reshuffled, resulting in several inversions in maize compared to sorghum and sugarcane. The results emphasize the fact that duplication will considerably complicate precise comparative mapping at the whole genome scale between maize and other Poaceae. PMID:24166631

  15. GENOMIC ANALYSIS OF A 1 MB REGION NEAR THE TELOMERE OF HESSIAN FLY CHROMOSOME X2 AND AVIRULENCE GENE VH13

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 da...

  16. Flagellar region 3b supports strong expression of integrated DNA and the highest chromosomal integration efficiency of the Escherichia coli flagellar regions

    PubMed Central

    Juhas, Mario; Ajioka, James W

    2015-01-01

    The Gram-negative bacterium Escherichia coli is routinely used as the chassis for a variety of biotechnology and synthetic biology applications. Identification and analysis of reliable chromosomal integration and expression target loci is crucial for E. coli engineering. Chromosomal loci differ significantly in their ability to support integration and expression of the integrated genetic circuits. In this study, we investigate E. coli K12 MG1655 flagellar regions 2 and 3b. Integration of the genetic circuit into seven and nine highly conserved genes of the flagellar regions 2 (motA, motB, flhD, flhE, cheW, cheY and cheZ) and 3b (fliE, F, G, J, K, L, M, P, R), respectively, showed significant variation in their ability to support chromosomal integration and expression of the integrated genetic circuit. While not reducing the growth of the engineered strains, the integrations into all 16 target sites led to the loss of motility. In addition to high expression, the flagellar region 3b supports the highest efficiency of integration of all E. coli K12 MG1655 flagellar regions and is therefore potentially the most suitable for the integration of synthetic genetic circuits. PMID:26074421

  17. Transcripts of the MHM region on the chicken Z chromosome accumulate as non-coding RNA in the nucleus of female cells adjacent to the DMRT1 locus.

    PubMed

    Teranishi, M; Shimada, Y; Hori, T; Nakabayashi, O; Kikuchi, T; Macleod, T; Pym, R; Sheldon, B; Solovei, I; Macgregor, H; Mizuno, S

    2001-01-01

    The male hypermethylated (MHM) region, located near the middle of the short arm of the Z chromosome of chickens, consists of approximately 210 tandem repeats of a BamHI 2.2-kb sequence unit. Cytosines of the CpG dinucleotides of this region are extensively methylated on the two Z chromosomes in the male but much less methylated on the single Z chromosome in the female. The state of methylation of the MHM region is established after fertilization by about the 1-day embryonic stage. The MHM region is transcribed only in the female from the particular strand into heterogeneous, high molecular-mass, non-coding RNA, which is accumulated at the site of transcription, adjacent to the DMRT1 locus, in the nucleus. The transcriptional silence of the MHM region in the male is most likely caused by the CpG methylation, since treatment of the male embryonic fibroblasts with 5-azacytidine results in hypo-methylation and active transcription of this region. In ZZW triploid chickens, MHM regions are hypomethylated and transcribed on the two Z chromosomes, whereas MHM regions are hypermethylated and transcriptionally inactive on the three Z chromosomes in ZZZ triploid chickens, suggesting a possible role of the W chromosome on the state of the MHM region. PMID:11321370

  18. Increased disomic homozygosity in the telomeric region of chromosome 21 among Down Syndrome individuals with duodenal atresia

    SciTech Connect

    Lamb, N.E.; Feingold, E.; Sherman, S.L.

    1994-09-01

    Although duodenal atresia (DA) is present in only 4-7% of all Down Syndrome (DS) individuals, 30-50% of all congenital duodenal atresias occur in the DS population, suggesting the presence of gene(s) on chromosome 21 that play an important role in intestinal development. We recently proposed a chromosome 21 gene dosage model to explain the phenotypic variance seen among DS individuals and presented a strategy to map genes involved in these phenotypic traits. We suggest that {open_quote}hyper-dosage{close_quote} resulting from normal allelic differences explains the phenotypic variation. A proportion of trisomic genotypes would exceed some activity threshold and express the trait. In affected individuals, this increase in expression is due to the presence of two identical copies of {open_quote}susceptibility{close_quote} allele, inherited from a heterozygous parent of origin. Individuals with trisomy 21 and a specific phenotypic defect should exhibit increased levels of disomic homozygosity in the region containing the gene involved in the defect`s etiology. These data can be used to map these genes. Using this approach, we have examined markers along the long arm of chromosome 21 among DS individuals with DA and determined the degree of disomic homozygosity at each marker. This frequency was compared to the level of disomic homozygosity among our entire DS study population consisting of approximately 380 DS families to test for linkage between DA and each marker. Preliminary analysis of 13 DS cases with DA indicates an increase in disomic homozygosity along the distal region of the chromosome, from HMG14 to D21S171, the most telomeric marker analyzed. An additional 15 cases are currently being analyzed to confirm and better define this candidate region.

  19. Narrowing a region on rat chromosome 13 that protects against hypertension in Dahl SS-13BN congenic strains.

    PubMed

    Moreno, Carol; Williams, Jan M; Lu, Limin; Liang, Mingyu; Lazar, Jozef; Jacob, Howard J; Cowley, Allen W; Roman, Richard J

    2011-04-01

    Transfer of chromosome 13 from the Brown Norway (BN) rat onto the Dahl salt-sensitive (SS) genetic background attenuates the development of hypertension, but the genes involved remain to be identified. The purpose of the present study was to confirm by telemetry that a congenic strain [SS.BN-(D13Hmgc37-D13Got22)/Mcwi, line 5], carrying a 13.4-Mb segment of BN chromosome 13 from position 32.4 to 45.8 Mb, is protected from the development of hypertension and then to narrow the region of interest by creating and phenotyping 11 additional subcongenic strains. Mean arterial pressure (MAP) rose from 118 ± 1 to 186 ± 5 mmHg in SS rats fed a high-salt diet (8.0% NaCl) for 3 wk. Protein excretion increased from 56 ± 11 to 365 ± 37 mg/day. In contrast, MAP only increased to 152 ± 9 mmHg in the line 5 congenic strain. Six subcongenic strains carrying segments of BN chromosome 13 from 32.4 and 38.2 Mb and from 39.9 to 45.8 Mb were not protected from the development of hypertension. In contrast, MAP was reduced by ∼30 mmHg in five strains, carrying a 1.9-Mb common segment of BN chromosome 13 from 38.5 to 40.4 Mb. Proteinuria was reduced by ∼50% in these strains. Sequencing studies did not identify any nonsynonymous single nucleotide polymorphisms in the coding region of the genes in this region. RT-PCR studies indicated that 4 of the 13 genes in this region were differentially expressed in the kidney of two subcongenic strains that were partially protected from hypertension vs. those that were not. These results narrow the region of interest on chromosome 13 from 13.4 Mb (159 genes) to a 1.9-Mb segment containing only 13 genes, of which 4 are differentially expressed in strains partially protected from the development of hypertension. PMID:21257920

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

    SciTech Connect

    Neiswanger, K.; Kaplan, B.; Hill, S.Y.

    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.

  1. Precise estimation of genomic regions controlling lodging resistance using a set of reciprocal chromosome segment substitution lines in rice

    PubMed Central

    Ookawa, Taiichiro; Aoba, Ryo; Yamamoto, Toshio; Ueda, Tadamasa; Takai, Toshiyuki; Fukuoka, Shuichi; Ando, Tsuyu; Adachi, Shunsuke; Matsuoka, Makoto; Ebitani, Takeshi; Kato, Yoichiro; Mulsanti, Indria Wahyu; Kishii, Masahiro; Reynolds, Matthew; Piñera, Francisco; Kotake, Toshihisa; Kawasaki, Shinji; Motobayashi, Takashi; Hirasawa, Tadashi

    2016-01-01

    Severe lodging has occurred in many improved rice varieties after the recent strong typhoons in East and Southeast Asian countries. The indica variety Takanari possesses strong culm characteristics due to its large section modulus, which indicates culm thickness, whereas the japonica variety Koshihikari is subject to substantial bending stress due to its thick cortical fibre tissue. To detect quantitative trait loci (QTLs) for lodging resistance and to eliminate the effects of genetic background, we used reciprocal chromosome segment substitution lines (CSSLs) derived from a cross between Koshihikari and Takanari. The oppositional effects of QTLs for section modulus were confirmed in both genetic backgrounds on chromosomes 1, 5 and 6, suggesting that these QTLs are not affected by the genetic background and are controlled independently by a single factor. The candidate region of a QTL for section modulus included SD1. The section modulus of NIL-sd1 was lower than that of Koshihikari, whereas the section modulus of NIL-SD1 was higher than that of Takanari. This result indicated that those regions regulate the culm thickness. The reciprocal effects of the QTLs for cortical fibre tissue thickness were confirmed in both genetic backgrounds on chromosome 9 using CSSLs. PMID:27465821

  2. A refined genetic map of the region of chromosome 17 surrounding the von recklinghausen neurofibromatosis (NF1) gene

    PubMed Central

    Diehl, Scott R.; Boehnke, Michael; Erickson, Robert P.; Ploughman, Lynn M.; Seiler, Kathleen A.; Lieberman, Janice L.; Clarke, H. Bush; Bruce, Melissa A.; Schorry, Elizabeth K.; Pericak-Vance, Margaret; O'Connell, Peter; Collins, Francis S.

    1989-01-01

    The von Recklinghausen neurofibromatosis (NF1) gene has been mapped to the pericentromeric region of chromosome 17. We conducted linkage analyses of NF1 by using 10 polymorphic DNA markers from this chromosomal region. We ascertained 20 American Caucasian NF1 families (163 individuals, 98 NF1 affected) in Michigan and Ohio and also studied a large family ascertained primarily in North Carolina. The following markers were used in this study: HHH202, TH17.19, D17Z1, ERBA1, EW203, EW206, EW207, EW301, CRI-L581, and CRI-L946. NF1 did not recombine with either TH17.19 or HHH202 in any of the informative meioses surveyed (maximum lod scores of 17.04 and 7.21, respectively, at a recombination fraction of .00), indicating that these markers map very close to the NF1 gene. We also report evidence of three instances of recombination between NF1 and the centromeric marker D17Z1 (maximum lod score of 13.43 at a recombination fraction of .04), as well as two crossovers between pairs of marker loci. We find no evidence of locus heterogeneity, and our results support the localization of the NF1 gene to proximal chromosome 17q. PMID:2491779

  3. Sensitized phenotypic screening identifies gene dosage sensitive region on chromosome 11 that predisposes to disease in mice

    PubMed Central

    Ermakova, Olga; Piszczek, Lukasz; Luciani, Luisa; Cavalli, Florence M G; Ferreira, Tiago; Farley, Dominika; Rizzo, Stefania; Paolicelli, Rosa Chiara; Al-Banchaabouchi, Mumna; Nerlov, Claus; Moriggl, Richard; Luscombe, Nicholas M; Gross, Cornelius

    2011-01-01

    The identification of susceptibility genes for human disease is a major goal of current biomedical research. Both sequence and structural variation have emerged as major genetic sources of phenotypic variability and growing evidence points to copy number variation as a particularly important source of susceptibility for disease. Here we propose and validate a strategy to identify genes in which changes in dosage alter susceptibility to disease-relevant phenotypes in the mouse. Our approach relies on sensitized phenotypic screening of megabase-sized chromosomal deletion and deficiency lines carrying altered copy numbers of ∼30 linked genes. This approach offers several advantages as a method to systematically identify genes involved in disease susceptibility. To examine the feasibility of such a screen, we performed sensitized phenotyping in five therapeutic areas (metabolic syndrome, immune dysfunction, atherosclerosis, cancer and behaviour) of a 0.8 Mb reciprocal chromosomal duplication and deficiency on chromosome 11 containing 27 genes. Gene dosage in the region significantly affected risk for high-fat diet-induced metabolic syndrome, antigen-induced immune hypersensitivity, ApoE-induced atherosclerosis, and home cage activity. Follow up studies on individual gene knockouts for two candidates in the region showed that copy number variation in Stat5 was responsible for the phenotypic variation in antigen-induced immune hypersensitivity and metabolic syndrome. These data demonstrate the power of sensitized phenotypic screening of segmental aneuploidy lines to identify disease susceptibility genes. PMID:21204268

  4. Precise estimation of genomic regions controlling lodging resistance using a set of reciprocal chromosome segment substitution lines in rice.

    PubMed

    Ookawa, Taiichiro; Aoba, Ryo; Yamamoto, Toshio; Ueda, Tadamasa; Takai, Toshiyuki; Fukuoka, Shuichi; Ando, Tsuyu; Adachi, Shunsuke; Matsuoka, Makoto; Ebitani, Takeshi; Kato, Yoichiro; Mulsanti, Indria Wahyu; Kishii, Masahiro; Reynolds, Matthew; Piñera, Francisco; Kotake, Toshihisa; Kawasaki, Shinji; Motobayashi, Takashi; Hirasawa, Tadashi

    2016-01-01

    Severe lodging has occurred in many improved rice varieties after the recent strong typhoons in East and Southeast Asian countries. The indica variety Takanari possesses strong culm characteristics due to its large section modulus, which indicates culm thickness, whereas the japonica variety Koshihikari is subject to substantial bending stress due to its thick cortical fibre tissue. To detect quantitative trait loci (QTLs) for lodging resistance and to eliminate the effects of genetic background, we used reciprocal chromosome segment substitution lines (CSSLs) derived from a cross between Koshihikari and Takanari. The oppositional effects of QTLs for section modulus were confirmed in both genetic backgrounds on chromosomes 1, 5 and 6, suggesting that these QTLs are not affected by the genetic background and are controlled independently by a single factor. The candidate region of a QTL for section modulus included SD1. The section modulus of NIL-sd1 was lower than that of Koshihikari, whereas the section modulus of NIL-SD1 was higher than that of Takanari. This result indicated that those regions regulate the culm thickness. The reciprocal effects of the QTLs for cortical fibre tissue thickness were confirmed in both genetic backgrounds on chromosome 9 using CSSLs. PMID:27465821

  5. Construction and characterization of a NotI linking library from human chromosome region 1q25-qter

    SciTech Connect

    Talmadge, C.B.; Zhen, Dong-Kai; Wang, Ji-Yi

    1995-09-01

    Chromosome 1q25-qter-specific NotI linking clones have been isolated from a NotI linking library that was constructed using DNA from MCH206.1 somatic cell hybrid cells. These cells contain chromosome 1q25-qter translocated to human chromosome Xp22 as the only human genetic material in mouse background. Sixty-eight NotI linking clones have been mapped by a combination of fluorescence in situ hybridization and R-banding to cytogenetic bands on the long arm of chromosome 1. The relative order of 11 NotI clones and their relation to known chromosome 1 markers have also been determined in 1q32 and 1q41, where the genes of Van der Woude and Usher syndrome type IIa have been previously mapped: cen-chr1.14-chr1.79-chr1.56-chr1.11-chr1.95-chr1.58 (chr1.74)-D1S70-chr1.15-chr1.82 (chr1.143)-chr1.62-D1S81-tel. The 1q32- and 1q41-specific NotI linking clones were sequenced in the vicinity of the NotI site. They were analyzed in terms of nucleotide composition, G+C content, frequency of CpG dinucleotides, and protein coding potentials. Most of the 1q32-q41-specific NotI linking clones were derived from CpG islands. Sequences of three NotI linking clones proved to be identical with known genes. Six of the remaining eight had a high potential for coding regions and shared short homologous regions with sequences in the GenBank database. The NotI linking clones and the identified CpG islands will provide valuable resources for constructing a long-range restriction map of chromosome 1q25-q44 and for the eventual isolation of disease genes of Van der Woude syndrome (1q32-q41) and Usher syndrome type IIa (1q41). 29 refs., 2 figs., 3 tabs.

  6. Gene identification and DNA sequence analysis in the GC-poor 20 megabase region of human chromosome 21.

    PubMed

    Yu, J; Tong, S; Shen, Y; Kao, F T

    1997-06-24

    In contrast to the distal half of the long arm of chromosome 21, the proximal half of approximately 20 megabases of DNA, including 21q11-21 bands, is low in GC content, CpG islands, and identified genes. Despite intensive searches, very few genes and cDNAs have been found in this region. Since the 21q11-21 region is associated with certain Down syndrome pathologies like mental retardation, the identification of relevant genes in this region is important. We used a different approach by constructing microdissection libraries specifically for this region and isolating unique sequence microclones for detailed molecular analysis. We found that this region is enriched with middle and low-copy repetitive sequences, and is also heavily methylated. By sequencing and homology analysis, we identified a significant number of genes/cDNAs, most of which appear to belong to gene families. In addition, we used unique sequence microclones in direct screening of cDNA libraries and isolated 12 cDNAs for this region. Thus, although the 21q11-21 region is gene poor, it is not completely devoid of genes/cDNAs. The presence of high proportions of middle and low-copy repetitive sequences in this region may have evolutionary significance in the genome organization and function of this region. Since 21q11-21 is heavily methylated, the expression of genes in this region may be regulated by a delicate balance of methylation and demethylation, and the presence of an additional copy of chromosome 21 may seriously disturb this balance and cause specific Down syndrome anomalies including mental retardation. PMID:9192657

  7. Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases.

    PubMed Central

    Le Beau, M M; Espinosa, R; Neuman, W L; Stock, W; Roulston, D; Larson, R A; Keinanen, M; Westbrook, C A

    1993-01-01

    Loss of a whole chromosome 5 or a deletion of its long arm (5q) is a recurring abnormality in malignant myeloid neoplasms. To determine the location of genes on 5q that may be involved in leukemogenesis, we examined the deleted chromosome 5 homologs in a series of 135 patients with malignant myeloid diseases. By comparing the breakpoints, we identified a small segment of 5q, consisting of band 5q31, that was deleted in each patient. This segment has been termed the critical region. Distal 5q contains a number of genes encoding growth factors, hormone receptors, and proteins involved in signal transduction or transcriptional regulation. These include several genes that are good candidates for a tumor-suppressor gene, as well as the genes encoding five hematopoietic growth factors (CSF2, IL3, IL4, IL5, and IL9). By using fluorescence in situ hybridization, we have refined the localization of these genes to 5q31.1 and have determined the order of these genes and of other markers within 5q31. By hybridizing probes to metaphase cells with overlapping deletions involving 5q31, we have narrowed the critical region to a small segment of 5q31 containing the EGR1 gene. The five hematopoietic growth factor genes and seven other genes are excluded from this region. The EGR1 gene was not deleted in nine other patients with acute myeloid leukemia who did not have abnormalities of chromosome 5. By physical mapping, the minimum size of the critical region was estimated to be 2.8 megabases. This cytogenetic map of 5q31, together with the molecular characterization of the critical region, will facilitate the identification of a putative tumor-suppressor gene in this band. PMID:8516290

  8. Control regions for chromosome replication are conserved with respect to sequence and location among Escherichia coli strains

    PubMed Central

    Frimodt-Møller, Jakob; Charbon, Godefroid; Krogfelt, Karen A.; Løbner-Olesen, Anders

    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 (datA dependent DnaAATP hydrolysis) whereas DnaA rejuvenation sequences 1 and 2 (DARS1 and DARS2) reactivate DnaAADP to DnaAATP. The structural organization of oriC, datA, DARS1, and DARS2 were found conserved among 59 fully sequenced E. coli genomes, with differences primarily in the non-functional spacer regions between key protein binding sites. The relative distances from oriC to datA, DARS1, and DARS2, respectively, was also conserved despite of large variations in genome size, suggesting that the gene dosage of either region is important for bacterial growth. Yet all three regions could be deleted alone or in combination without loss of viability. 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 advantage has contributed to conservation of both sequence and chromosomal location for datA, DARS1, and DARS2. PMID:26441936

  9. SYNAPTONEMAL COMPLEX ABERRATIONS IN THE PSEUDOAUTOSOMAL REGION OF X,Y CHROMOSOMES IN IRRADIATED HAMSTERS

    EPA Science Inventory

    Armenian hamsters were treated with X-radiation, bleomycin or amsacrine (m-AMSA) and the effects on meiotic chromosomes determined by electron microscopic analysis of synaptonemal complex (SC) formation. achytene cells were analyzed five or six days following their treatment at p...

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

    SciTech Connect

    Sunden, S.L.F.; Nichols, B.E.; Alward, W.L.M.

    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).

  11. The First Cytogenetic Data on Strumigenys louisianae Roger, 1863 (Formicidae: Myrmicinae: Dacetini): The Lowest Chromosome Number in the Hymenoptera of the Neotropical Region

    PubMed Central

    Alves-Silva, Ana Paula; Barros, Luísa Antônia Campos; Chaul, Júlio Cézar Mário; Pompolo, Silvia das Graças

    2014-01-01

    In the present study, the first cytogenetic data was obtained for the ant species Strumigenys louisianae, from a genus possessing no previous cytogenetic data for the Neotropical region. The chromosome number observed was 2n = 4, all possessing metacentric morphology. Blocks rich in GC base pairs were observed in the interstitial region of the short arm of the largest chromosome pair, which may indicate that this region corresponds to the NORs. The referred species presented the lowest chromosome number observed for the subfamily Myrmicinae and for the Hymenoptera found in the Neotropical region. Observation of a low chromosome number karyotype has been described in Myrmecia croslandi, in which the occurrence of tandem fusions accounts for the most probable rearrangement for its formation. The accumulation of cytogenetic data may carry crucial information to ensure deeper understanding of the systematics of the tribe Dacetini. PMID:25379715

  12. Peopling of the North Circumpolar Region – Insights from Y Chromosome STR and SNP Typing of Greenlanders

    PubMed Central

    Olofsson, Jill Katharina; Pereira, Vania; Børsting, Claus; Morling, Niels

    2015-01-01

    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. PMID:25635810

  13. Inversion of the Chromosomal Region between Two Mating Type Loci Switches the Mating Type in Hansenula polymorpha

    PubMed Central

    Maekawa, Hiromi; Kaneko, Yoshinobu

    2014-01-01

    Yeast mating type is determined by the genotype at the mating type locus (MAT). In homothallic (self-fertile) Saccharomycotina such as Saccharomyces cerevisiae and Kluveromyces lactis, high-efficiency switching between a and α mating types enables mating. Two silent mating type cassettes, in addition to an active MAT locus, are essential components of the mating type switching mechanism. In this study, we investigated the structure and functions of mating type genes in H. polymorpha (also designated as Ogataea polymorpha). The H. polymorpha genome was found to harbor two MAT loci, MAT1 and MAT2, that are ∼18 kb apart on the same chromosome. MAT1-encoded α1 specifies α cell identity, whereas none of the mating type genes were required for a identity and mating. MAT1-encoded α2 and MAT2-encoded a1 were, however, essential for meiosis. When present in the location next to SLA2 and SUI1 genes, MAT1 or MAT2 was transcriptionally active, while the other was repressed. An inversion of the MAT intervening region was induced by nutrient limitation, resulting in the swapping of the chromosomal locations of two MAT loci, and hence switching of mating type identity. Inversion-deficient mutants exhibited severe defects only in mating with each other, suggesting that this inversion is the mechanism of mating type switching and homothallism. This chromosomal inversion-based mechanism represents a novel form of mating type switching that requires only two MAT loci. PMID:25412462

  14. Assembly and analysis of cosmid contigs in the CEA-gene family region of human chromosome 19.

    PubMed Central

    Tynan, K; Olsen, A; Trask, B; de Jong, P; Thompson, J; Zimmermann, W; Carrano, A; Mohrenweiser, H

    1992-01-01

    The carcinoembryonic antigen (CEA)-like genes are members of a large gene family which is part of the immunoglobulin superfamily. The CEA family is divided into two major subgroups, the CEA-subgroup and the pregnancy-specific glycoprotein (PSG)-subgroup. In the course of an effort to develop a set of overlapping cosmids spanning human chromosome 19, we identified 245 cosmids in a human chromosome 19 cosmid library (6-7X redundant) by hybridization with an IgC-like domain fragment of the CEA gene. A fluorescence-based restriction enzyme digest fingerprinting strategy was used to assemble 212 probe-positive cosmids, along with 115 additional cosmids from a collection of approximately 8,000 randomly selected cosmids, into five contigs. Two of the contigs contain CEA-subgroup genes while the remaining three contigs contain PSG-subgroup genes. These five contigs range in size from 100 kb to over 300 kb and span an estimated 1 Mb. The CEA-like gene family was determined by fluorescence in situ hybridization to map in the q13.1-q13.2 region of human chromosome 19. Analysis of the two CEA-subgroup contigs provided verification of the contig assembly strategy and insight into the organization of 9 CEA-subgroup genes. PMID:1579453

  15. Molecular cytogenetic analysis of Inv Dup(15) chromosomes, using probes specific for the Pradar-Willi/Angelman syndrome region: Clinical implications

    SciTech Connect

    Leana-Cox, J. ); Jenkins, L. ); Palmer, C.G.; Plattner, R. ); Sheppard, L. ); Flejter, W.L. ); Zackowski, J. ); Tsien, F. ); Schwartz, S. )

    1994-05-01

    Twenty-seven cases of inverted duplications of chromosome 15 (inv dup[15]) were investigated by FISH with two DNA probes specific for the Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on proximal 15q. Sixteen of the marker chromosomes displayed two copies of each probe, while in the remaining 11 markers no hybridization was observed. A significant association was found between the presence of this region and an abnormal phenotype (P<.01). This is the largest study to date of inv dup(15) chromosomes, that uses molecular cytogenetic methods and is the first to report a significant association between the presence of a specific chromosomal region in such markers and an abnormal phenotype. 30 refs., 1 fig., 4 tabs.

  16. YAC contigs of the Rab1 and wobbler (wr) spinal muscular atrophy gene region on proximal mouse chromosome 11 and of the homologous region on human chromosome 2p

    SciTech Connect

    Wedemeyer, N.; Lengeling, A.; Ronsiek, M.

    1996-03-05

    Despite rapid progress in the physical characterization of murine and human genomes, little molecular information is available on certain regions, e.g., proximal mouse chromosome 11 (Chr 11) and human chromosome 2p (Chr2p). We have localized the wobbler spinal atrophy gene wr to proximal mouse Chr 11, tightly linked to Rab1, a gene coding for a small GTP-binding protein, and Glns-ps1, an intronless pseudogene of the glutamine synthetase gene. We have not used these markers to construct a 1.3-Mb yeast artificial chromosome (YAC) contig of the Rab1 region on mouse Chr 11. Four YAC clones isolated from two independent YAC libraries were characterized by rare-cutting analysis, fluorescence in situ hybridization (FISH), and sequence-tagged site (STS) isolation and mapping. Rab1 and Glns-ps1 were found to be only 200 kb apart. A potential CpG island near a methylated NarI site and a trapped exon, ETG1.1, were found over 250 kb from Rab1. Two overlapping YACs were identified that contained a 150-kb region of human Chr 2p, comprising the RAB1 locus, AHY1.1, and the human homologue of ETG1.1, indicating a high degree of conservation of this region in the two species. We mapped AHY1.1 and thus human RAB1 on Chr 2p13.4-p14 using somatic cell hybrids and a radiation hybrid panel, thus extending a known region of conserved synteny between mouse Chr 11 and human Chr 2p. Recently, the gene LMGMD2B for a human recessive neuromuscular disease, limb girdle muscular dystrophy type 2B, has been mapped to 2p13-p16. The conservation between the mouse Rab1 and human RAB1 regions will be helpful in identifying candidate genes for the wobbler spinal muscular atrophy and in clarifying a possible relationship between wr and LMGMD2B. 33 refs., 7 figs., 3 tabs.

  17. The mouse mutation sarcosinemia (sar) maps to chromosome 2 in a region homologous to human 9q33-q34

    SciTech Connect

    Brunialti, A.L.B.; Guenet, J.L.; Harding, C.O.; Wolff, J.A.

    1996-08-15

    The autosomal recessive mouse mutation sarcosinemia (sar), which was discovered segregating in the progeny of a male whose premeiotic germ cells had been treated with the mutagen ethylnitrosourea, is characterized by a deficiency in sarcosine dehydrogenase activity. Using an intersubspecific cross, we mapped the sar locus to mouse chromosome 2, approximately 15-18 cM from the centromere. The genetic localization of this locus in the mouse allows the identification of a candidate region in human (9q33-q34) where the homologous disease should map. 15 refs., 2 figs.

  18. Genetic analysis of Drosophila melanogaster polytene chromosome region 44D-45F: loci required for viability and fertility.

    PubMed Central

    Mohr, Stephanie E; Boswell, Robert E

    2002-01-01

    A genetic screen to identify mutations in genes in the 45A region on the right arm of chromosome 2 that are involved in oogenesis in Drosophila was undertaken. Several lethal but no female sterile mutations in the region had previously been identified in screens for P-element insertion or utilizing X rays or EMS as a mutagen. Here we report the identification of EMS-induced mutations in 21 essential loci in the 45D-45F region, including 13 previously unidentified loci. In addition, we isolated three mutant alleles of a newly identified locus required for fertility, sine prole. Mutations in sine prole disrupt spermatogenesis at or before individualization of spermatozoa and cause multiple defects in oogenesis, including inappropriate division of the germline cyst and arrest of oogenesis at stage 4. PMID:11973305

  19. Three-region specific microdissection libraries for the long arm of human chromosome 2, regions q33-q35, q31-q32, and q23-q24

    SciTech Connect

    Yu, J.; Tong, S.; Whittier, A.

    1995-09-01

    Three region-specific libraries have been constructed from the long arm of human chromosome 2, including regions 2q33-35 (2Q2 library), 2q31-32 (2Q3) and 2q23-24 (2Q4). Chromosome microdissection and the MboI linker-adaptor microcloning techniques were used in constructing these libraries. The libraries comprised hundreds of thousands of microclones in each library. Approximately half of the microclones in the library contained unique or low-copy number sequence inserts. The insert sizes ranged between 50 and 800 bp, with a mean of 130-190 bp. Southern blot analysis of individual unique sequence microclones showed that 70-94% of the microclones were derived from the dissected region. 31 unique sequence microclones from the 2Q2 library, 31 from 2Q3, and 30 from 2Q4, were analyzed for insert sizes, the hybridizing genomic HindIII fragment sizes, and cross-hybridization to rodent species. These libraries and the short insert microclones derived from the libraries should be useful for high resolution physical mapping, sequence-ready reagents for large scale genomic sequencing, and positional cloning of disease-related genes assigned to these regions, e.g. the recessive familial amyotrophic lateral sclerosis assigned to 2q33-q35, and a type I diabetes susceptibility gene to 2q31-q33. 17 refs., 5 figs., 2 tabs.

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

    SciTech Connect

    Ohira, Miki; Suzuki, Kazunobu |; Ichikawa, Hitoshi

    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.

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

    PubMed Central

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

    2016-01-01

    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 (SkK) that causes nearly all surviving meiotic progeny from an SkK × Spore killer-susceptible (SkS) cross to inherit the SkK allele. SkK 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 SkK × SkS 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 SkK to a contiguous 102 kb interval of chromosome V, herein referred to as the Sk region. Relative to SkS genotypes, SkK genotypes have one extra gene within this region for a total of 42 genes. The additional gene in SkK 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. PMID:27317777

  2. Fine Mapping of Candidate Regions for Bipolar Disorder Provides Strong Evidence for Susceptibility Loci on Chromosomes 7q

    PubMed Central

    Xu, Haiyan; Cheng, Rong; Juo, Suh-Hang; Liu, Jianjun; Loth, Jo Ellen; Endicott, Jean; Gilliam, Conrad; Baron, Miron

    2010-01-01

    Genomewide scans of bipolar disorder (BP) have not produced consistent linkage findings. Follow-up studies using enlarged samples and enhanced marker density can bolster or refute claims of linkage and pave the way to gene discovery. We conducted linkage and association analyses, using a ~3-cM density map of 10 candidate regions, in a large BP pedigree sample (865 individuals from 56 pedigrees). The candidate regions were identified in a previous 10-cM genome-wide scan using a subset of this sample (373 individuals from 40 pedigrees). The present sample consists of the expanded original pedigrees (‘core’ pedigrees) and 16 additional pedigrees. We obtained experiment-wide significant linkage on chromosome 7q34 (LOD score 3.53, p<0.001), substantially stronger than that observed in the genome-wide scan. Support for linkage was sustained on chromosomes 2p13, 4q31, 8q13, 13q32, 14q21 and 17q11, though at a more modest level. Family-based association analysis was consistent with the linkage results at all regions with linkage evidence, except 4q an 8q, but the results fell short of statistical significance. Three of the previously implicated regions – 9q31, 10q21 and 10q24 – showed substantial reduction in evidence of linkage. Our results strongly support 7q34 as a region harboring susceptibility locus for BP. Somewhat lesser, yet notable support was obtained for 2p13, 4q31, 8q13, 13q32, 14q21 and 17q11. These regions could be considered prime candidates for future gene finding efforts. PMID:21302345

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

    PubMed

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

    2016-01-01

    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. PMID:27317777

  4. Ovarian cancer has frequent loss of heterozygosity at chromosome 12p12.3-13.1 (region of TEL and Kip1 loci) and chromosome 12q23-ter: evidence for two new tumour-suppressor genes.

    PubMed Central

    Hatta, Y.; Takeuchi, S.; Yokota, J.; Koeffler, H. P.

    1997-01-01

    Identification of the key genetic alterations leading to ovarian cancer is in its infancy. Polymerase chain reaction (PCR)-based analysis of loss of heterozygosity (LOH) is a powerful method for detecting regions of altered tumour-suppressor genes. Focusing on chromosome 12, we examined 23 ovarian cancer samples for LOH using 31 highly polymorphic microsatellite markers and found the chromosomal localization of two putative tumour-suppressor genes. Two commonly deleted regions were 12p12.3-13.1 in 6/23 (26%) and 12q23-ter in 7/23 (30%) samples. LOH on chromosome 12 was more common in late-stage ovarian carcinomas. The region of LOH at 12p12.3-13.1 includes the genes that code for the ETS-family transcriptional factor, known as TEL, and the cyclin-dependent kinase inhibitor, known as p27Kip1. Mutational analysis of both TEL and p27Kip1 using single-strand conformation polymorphism (SSCP) showed no abnormalities, suggesting that the altered gene in this region is neither of these genes. Taken together, our data suggest that new tumour-suppressor genes in the region of chromosomes 12p12.3-13.1 and 12q23-ter may be involved in the development of ovarian cancer. Images Figure 1 Figure 2 Figure 4 PMID:9155043

  5. Comparative mapping of DNA probes derived from the V{sub k} immunoglobulin gene regions on human and great ape chromosomes by fluorescence in situ hybridization

    SciTech Connect

    Arnold, N.; Wienberg, J.; Ermert, K.

    1995-03-01

    Fluorescence in situ hybridization (FISH) of cosmid clones of human V{sub K} gene regions to human and primate chromosomes contributed to the dating of chromosome reorganizations in evolution. A clone from the K locus at 2p11-p12 (cos 106) hybridized to the assumed homologous chromosome bands in the chimpanzees Pan troglodytes (PTR) and P. paniscus (PPA), the Gorilla gorilla (GGO), and the orangutan Pongo Pygmaeus (PPY). Human and both chimpanzees differed from gorilla and orangutan by the mapping of cos 170, a clone derived from chromosome 2cen-q11.2; the transposition of this orphon to the other side of the centromere can, therefore, be dated after the human/chimpanzee and gorilla divergence. Hybridization to homologous bands was also found with a cosmid clone containing a V{sub K}I orphon located on chromosome 1 (cos 115, main signal at 1q31-q32), although the probe is not fully unique. Also, a clone derived from the orphon V{sub K} region on chromosome 22q11 (cos 121) hybridized to the homologous bands in the great apes. This indicates that the orphons on human chromosomes 1 and 22 had been translocated early in primate evolution. 18 refs., 2 figs.

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

    SciTech Connect

    Burkin, D.J.; Jones, C. ); Kimbro, K.S.; Taylor, M.W. ); Barr, B.L.; Gupta, S.L. )

    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.

  7. Temporal Fluctuation in North East Baltic Sea Region Cattle Population Revealed by Mitochondrial and Y-Chromosomal DNA Analyses

    PubMed Central

    Niemi, Marianna; Bläuer, Auli; Iso-Touru, Terhi; Harjula, Janne; Nyström Edmark, Veronica; Rannamäe, Eve; Lõugas, Lembi; Sajantila, Antti; Lidén, Kerstin; Taavitsainen, Jussi-Pekka

    2015-01-01

    Background Ancient DNA analysis offers a way to detect changes in populations over time. To date, most studies of ancient cattle have focused on their domestication in prehistory, while only a limited number of studies have analysed later periods. Conversely, the genetic structure of modern cattle populations is well known given the undertaking of several molecular and population genetic studies. Results Bones and teeth from ancient cattle populations from the North-East Baltic Sea region dated to the Prehistoric (Late Bronze and Iron Age, 5 samples), Medieval (14), and Post-Medieval (26) periods were investigated by sequencing 667 base pairs (bp) from the mitochondrial DNA (mtDNA) and 155 bp of intron 19 in the Y-chromosomal UTY gene. Comparison of maternal (mtDNA haplotypes) genetic diversity in ancient cattle (45 samples) with modern cattle populations in Europe and Asia (2094 samples) revealed 30 ancient mtDNA haplotypes, 24 of which were shared with modern breeds, while 6 were unique to the ancient samples. Of seven Y-chromosomal sequences determined from ancient samples, six were Y2 and one Y1 haplotype. Combined data including Swedish samples from the same periods (64 samples) was compared with the occurrence of Y-chromosomal haplotypes in modern cattle (1614 samples). Conclusions The diversity of haplogroups was highest in the Prehistoric samples, where many haplotypes were unique. The Medieval and Post-Medieval samples also show a high diversity with new haplotypes. Some of these haplotypes have become frequent in modern breeds in the Nordic Countries and North-Western Russia while other haplotypes have remained in only a few local breeds or seem to have been lost. A temporal shift in Y-chromosomal haplotypes from Y2 to Y1 was detected that corresponds with the appearance of new mtDNA haplotypes in the Medieval and Post-Medieval period. This suggests a replacement of the Prehistoric mtDNA and Y chromosomal haplotypes by new types of cattle. PMID:25992976

  8. Tetralogy of Fallot associated with deletion in the DiGeorge region of chromosome 22 (22q11)

    SciTech Connect

    D`Angelo, J.A.; Pillers, D.M.; Jett, P.L.

    1994-09-01

    Cardiac conotruncal defects, such as Tetralogy of Fallot (TOF), are associated with DiGeorge syndrome which has been mapped to the q11 region of chromosome 22 and includes abnormalities of neural crest and branchial arch development. Patients with conotruncal defects and velo-cardio-facial syndrome may have defects in the 22q11 region but not show the complete DiGeorge phenotype consisting of cardiac, thymus, and parathyroid abnormalities. We report two neonates with TOF and small deletions in the DiGeorge region of chromosome 22 (46,XX,del(22)(q11.21q11.23) and 46,XY,del(22)(q11.2q11.2)) using both high-resolution cytogenetics and fluorescence in situ hybridization (FISH). The first patient is a female with TOF and a family history of congenital heart disease. The mother has pulmonic stenosis and a right-sided aortic arch, one brother has TOF, and a second brother has a large VSD. The patient had intrauterine growth retardation and had thrombocytopenia due to maternal IgG platelet-directed autoantibody. Lymphocyte populations, both T and B cells, were reduced in number but responded normally to stimulation. The findings were not attributed to a DiGeorge phenotype. Although she had transient neonatal hypocalcemia, her parathyroid hormone level was normal. The patient was not dysmorphic in the newborn period but her mother had features consistent with velo-cardio-facial syndrome. The second patient was a male with TOF who was not dysmorphic and had no other significant clinical findings and no family history of heart disease. Lymphocyte testing did not reveal a specific immunodeficiency. No significant postnatal hypocalcemia was noted. These cases illustrate that there is a wide spectrum of clinical features associated with defects of the 22q11 region. We recommend karyotype analysis, including FISH probes specific to the DiGeorge region, in any patient with conotruncal cardiac defects.

  9. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits

    PubMed Central

    Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca e; Mundim, Gabriel Borges

    2016-01-01

    Abstract The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis. PMID:27007903

  10. Fine-Scale Heterogeneity in Crossover Rate in the garnet-scalloped Region of the Drosophila melanogaster X Chromosome

    PubMed Central

    Singh, Nadia D.; Stone, Eric A.; Aquadro, Charles F.; Clark, Andrew G.

    2013-01-01

    Homologous recombination affects myriad aspects of genome evolution, from standing levels of nucleotide diversity to the efficacy of natural selection. Rates of crossing over show marked variability at all scales surveyed, including species-, population-, and individual-level differences. Even within genomes, crossovers are nonrandomly distributed in a wide diversity of taxa. Although intra- and intergenomic heterogeneities in crossover distribution have been documented in Drosophila, the scale and degree of crossover rate heterogeneity remain unclear. In addition, the genetic features mediating this heterogeneity are unknown. Here we quantify fine-scale heterogeneity in crossover distribution in a 2.1-Mb region of the Drosophila melanogaster X chromosome by localizing crossover breakpoints in 2500 individuals, each containing a single crossover in this specific X chromosome region. We show 90-fold variation in rates of crossing over at a 5-kb scale, place this variation in the context of several aspects of genome evolution, and identify several genetic features associated with crossover rates. Our results shed new light on the scale and magnitude of crossover rate heterogeneity in D. melanogaster and highlight potential features mediating this heterogeneity. PMID:23410829

  11. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits.

    PubMed

    Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca E; Mundim, Gabriel Borges

    2016-03-01

    The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis. PMID:27007903

  12. A 6-Mb yeast artificial chromosome contig and long-range physical map encompassing the region on chromosome 12q15 frequently rearranged in a variety of benign solid tumors

    SciTech Connect

    Schoenmakers, E.F.P.M.; Geurts, J.M.W.; Kools, P.F.J.; Mols, R.

    1995-10-10

    Cytogenetic analysis of a variety of benign solid tumors, among which uterine leiomyoma, lipoma, pleomorphic salivary gland adenoma, and pulmonary chondroid hamartoma, has indicated that these tumors often display chromosome breakpoints in region q13-q15 of chromosome 12. In previous studies, we have reported that these breakpoints map between locus D12S8 and the CHOP gene, the latter of which has been shown to be consistently rearranged in myxoid liposarcomas with t(12;16)(q13;p11). Here, we report directional chromosome walking studies starting from D12S8 and resulting in the construction of a YAC contig of about 6 Mb. This YAC contig, whose orientation on chromosome 12 was determined by double-color fluorescence in situ hybridization (FISH) analysis, has at least double coverage and consists of 75 overlapping YAC clones, all isolated from CEPH YAC libraries. Their insert sizes were estimated by contour-clamped homogeneous electric field (CHEF) gel electrophoresis. On the basis of YAC end-derived DNA markers and sequence-tagged sites (STSs), with an average spacing of approximately 70 kb, as well as restriction enzyme analysis, a long-range physical map was established for the 6-Mb DNA region of chromosome 12 covered by the YAC contig. Within the YAC contig, the relative positions of various known genes, an expressed sequence-tagged site, and a number of CEPH/Genethon polymorphic markers were determined. The latter data allow full integration of our mapping data with those obtained by CEPH/Genethon as well as those reported at the Second International Workshop on Human Chromosome 12 Mapping. Finally, this YAC contig constitutes the basis for the construction of a transcriptional map of this region and is likely to facilitate identification of genes involved in the formation of various benign solid tumor types. 56 refs., 1 fig., 2 tabs.

  13. Delineation of the critical deletion region for congenital heart defects, on chromosome 8p23.1.

    PubMed Central

    Devriendt, K; Matthijs, G; Van Dael, R; Gewillig, M; Eyskens, B; Hjalgrim, H; Dolmer, B; McGaughran, J; Bröndum-Nielsen, K; Marynen, P; Fryns, J P; Vermeesch, J R

    1999-01-01

    Deletions in the distal region of chromosome 8p (del8p) are associated with congenital heart malformations. Other major manifestations include microcephaly, intrauterine growth retardation, mental retardation, and a characteristic hyperactive, impulsive behavior. We studied genotype-phenotype correlations in nine unrelated patients with a de novo del8p, by using the combination of classic cytogenetics, FISH, and the analysis of polymorphic DNA markers. With the exception of one large terminal deletion, all deletions were interstitial. In five patients, a commonly deleted region of approximately 6 Mb was present, with breakpoints clustering in the same regions. One patient without a heart defect or microcephaly but with mild mental retardation and characteristic behavior had a smaller deletion within this commonly deleted region. Two patients without a heart defect had a more proximal interstitial deletion that did not overlap with the commonly deleted region. Taken together, these data allowed us to define the critical deletion regions for the major features of a del8p. PMID:10090897

  14. Fine Mapping of a GWAS-Derived Obesity Candidate Region on Chromosome 16p11.2

    PubMed Central

    Jarick, Ivonne; Pütter, Carolin; Göbel, Maria; Horn, Lucie; Struve, Christoph; Haas, Katharina; Knoll, Nadja; Grallert, Harald; Illig, Thomas; Reinehr, Thomas; Wang, Hai-Jun; Hebebrand, Johannes; Hinney, Anke

    2015-01-01

    Introduction Large-scale genome-wide association studies (GWASs) have identified 97 chromosomal loci associated with increased body mass index in population-based studies on adults. One of these SNPs, rs7359397, tags a large region (approx. 1MB) with high linkage disequilibrium (r²>0.7), which comprises five genes (SH2B1, APOBR, sulfotransferases: SULT1A1 and SULT1A2, TUFM). We had previously described a rare mutation in SH2B1 solely identified in extremely obese individuals but not in lean controls. Methods The coding regions of the genes APOBR, SULT1A1, SULT1A2, and TUFM were screened for mutations (dHPLC, SSCP, Sanger re-sequencing) in 95 extremely obese children and adolescents. Detected non-synonymous variants were genotyped (TaqMan SNP Genotyping, MALDI TOF, PCR-RFLP) in independent large study groups (up to 3,210 extremely obese/overweight cases, 485 lean controls and 615 obesity trios). In silico tools were used for the prediction of potential functional effects of detected variants. Results Except for TUFM we detected non-synonymous variants in all screened genes. Two polymorphisms rs180743 (APOBR p.Pro428Ala) and rs3833080 (APOBR p.Gly369_Asp370del9) showed nominal association to (extreme) obesity (uncorrected p = 0.003 and p = 0.002, respectively). In silico analyses predicted a functional implication for rs180743 (APOBR p.Pro428Ala). Both APOBR variants are located in the repetitive region with unknown function. Conclusion Variants in APOBR contributed as strongly as variants in SH2B1 to the association with extreme obesity in the chromosomal region chr16p11.2. In silico analyses implied no functional effect of several of the detected variants. Further in vitro or in vivo analyses on the functional implications of the obesity associated variants are warranted. PMID:25955518

  15. A chromosomal region 7p11.2 transcript map: its development and application to the study of EGFR amplicons in glioblastoma.

    PubMed Central

    Eley, Greg D.; Reiter, Jill L.; Pandita, Ajay; Park, Soyeon; Jenkins, Robert B.; Maihle, Nita J.; James, C. David

    2002-01-01

    Cumulative information available about the organization of amplified chromosomal regions in human tumors suggests that the amplification repeat units, or amplicons, can be of a simple or complex nature. For the former, amplified regions generally retain their native chromosomal configuration and involve a single amplification target sequence. For complex amplicons, amplified DNAs usually undergo substantial reorganization relative to the normal chromosomal regions from which they evolve, and the regions subject to amplification may contain multiple target sequences. Previous efforts to characterize the 7p11.2 epidermal growth factor receptor ) amplicon in glioblastoma have relied primarily on the use of markers positioned by linkage analysis and/or radiation hybrid mapping, both of which are known to have the potential for being inaccurate when attempting to order loci over relatively short (<1 Mb) chromosomal regions. Due to the limited resolution of genetic maps that have been established through the use of these approaches, we have constructed a 2-Mb bacterial and P1-derived artificial chromosome (BAC-PAC) contig for the EGFR region and have applied markers positioned on its associated physical map to the analysis of 7p11.2 amplifications in a series of glioblastomas. Our data indicate that EGFR is the sole amplification target within the mapped region, although there are several additional 7p11.2 genes that can be coamplified and overexpressed with EGFR. Furthermore, these results are consistent with EGFR amplicons retaining the same organization as the native chromosome 7p11.2 region from which they are derived. PMID:11916499

  16. Molecular and Cytogenetic Analysis of the Heterochromatin-Euchromatin Junction Region of the Drosophila Melanogaster X Chromosome Using Cloned DNA Sequences

    PubMed Central

    Yamamoto, M. T.; Mitchelson, A.; Tudor, M.; O'Hare, K.; Davies, J. A.; Miklos, GLG.

    1990-01-01

    We have used three cloned DNA sequences consisting of (1) part of the suppressor of forked transcription unit, (2) a cloned 359-bp satellite, and (3), a type I ribosomal insertion, to examine the structure of the base of the X chromosome of Drosophila melanogaster where different chromatin types are found in juxtaposition. A DNA probe from the suppressor of forked locus hybridizes exclusively to the very proximal polytenized part of division 20, which forms part of the β-heterochromatin of the chromocenter. The cloned 359-bp satellite sequence, which derives from the proximal mitotic heterochromatin between the centromere and the ribosomal genes, hybridizes to the under replicated α-heterochromatin of the chromocenter. The type I insertion sequence, which has major locations in the ribosomal genes and in the distal mitotic heterochromatin of the X chromosome, hybridizes as expected to the nucleolus but does not hybridize to the β-heterochromatic division 20 of the polytene X chromosome. Our molecular data reveal that the suppressor of forked locus, which on cytogenetic grounds is the most proximal ordinary gene on the X chromosome, is very close to the junction of the polytenized and non-polytenized region of the X chromosome. The data have implications for the structure of β-heterochromatin-α-heterochromatin junction zones in both mitotic and polytene chromosomes, and are discussed with reference to models of chromosome structure. PMID:2118871

  17. Adipose and muscle tissue gene expression of two genes (NCAPG and LCORL) located in a chromosomal region associated with cattle feed intake and gain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 mark...

  18. Adipose and muscle tissue expression of two genes (NCAPG and LCORL) located in a chromosomal region associated with cattle feed intake and gain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. We previously identified genetic ...

  19. A Locus on Chromosome 8 Controlling Tumor Regionality -- a New Type of Tumor Diversity in the Mouse Lung

    PubMed Central

    Quan, Lei; Hutson, Alan; Demant, Peter

    2010-01-01

    Regional specificity of lung tumor formation has rarely been studied in mouse or human. By using crosses of strains semi-congenic for lung cancer susceptibility locus Sluc20, we have analyzed the genetic influences of Sluc20 and five other loci on tumor regionality in the mouse lung. We have mapped Sluc20 to a 27.92MB proximal region of chromosome 8 and found that it controls the number and load of only those tumors that surround or are directly adjacent to the bronchi or bronchioli (peribronchial tumors). These tumors lie outside the bronchial basement membrane and tend to reach a larger size than the tumors at other locations in the lung. Similarly to tumors of alveolar lineage at other locations, peribronchial tumors stain with SP-C but not CC-10 antibody. The effects of Sluc20 alleles are additive as the number of peribronchial tumors in heterozygotes is intermediate. These findings reveal that tumor regionality in the mouse lung, which represents a novel level of lung tumor heterogeneity, is under specific genetic control. The identification of genes controlling lung tumor regionality will provide novel insights into biology of lung tumors and potentially improve the possibilities of individualized prognosis and treatment in human lung cancer. PMID:19847808

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

    PubMed

    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. PMID:25765000

  1. Physical mapping of the holoprosencephaly critical region in 21q22.3, exclusion of SIM2 as a candidate gene for holoprosencephaly, and mapping of SIM2 to a region of chromosome 21 important for Down syndrome

    SciTech Connect

    Muenke, M.; Bone, L.J.; Mitchell, H.F.

    1995-11-01

    We set out to define the holoprosencephaly (HPE) critical region on chromosome 21 and also to determine whether there were human homologues of the Drosophila single-minded (sim) gene that might be involved in HPE. Analysis of somatic cell hybrid clones that contained rearranged chromosomes 21 from HPE patients defined the HPE minimal critical region in 21q22.3 as D21S113 to qter. We used established somatic cell hybrid mapping panels to map SIM2 to chromosome 21 within subbands q22.2-q22.3. Analysis of the HPE patient-derived somatic cell hybrids showed that SIM2 is not deleted in two of three patients and thus is not a likely candidate for HPE1, the HPE gene on chromosome 21. However, SIM2 does map within the Down syndrome critical region and thus is a candidate gene that might contribute to the Down syndrome phenotype. 31 refs., 2 figs., 1 tab.

  2. Linkage analysis of primary open-angle glaucoma excludes the juvenile glaucoma region on chromosome 1q

    SciTech Connect

    Wirtz, M.K.; Acott, T.S.; Samples, J.R. |

    1994-09-01

    The gene for one form of juvenile glaucoma has been mapped to chromosome 1q21-q31. This raises the possibility of primary open-angle glaucoma (POAG) also mapping to this region if the same defective gene causes both diseases. To ask this question linkage analysis was performed on a large POAG kindred. Blood samples or skin biopsies were obtained from 40 members of this family. Individuals were diagnosed as having POAG if they met two or more of the following criteria: (1) Visual field defects compatible with glaucoma on automated perimetry; (2) Optic nerve head and/or nerve fiber layer analysis compatible with glaucomatous damage; (3) high intraocular pressures (> 20 mm Hg). Patients were considered glaucoma suspects if they only met one criterion. These individuals were excluded from the analysis. Of the 40 members, seven were diagnosed with POAG; four were termed suspects. The earliest age of onset was 38 years old, while the average age of onset was 65 years old. We performed two-point and multipoint linkage analysis, using five markers which encompass the region 1q21-q31; specifically, D1S194, D1S210, D1S212, D1S191 and LAMB2. Two-point lod scores excluded tight linkage with all markers except D1S212 (maximum lod score of 1.07 at theta = 0.0). In the multipoint analysis, including D1S210-D1S212-LAMB2 and POAG, the entire 11 cM region spanned by these markers was excluded for linkage with POAG; that is, lod scores were < -2.0. In conclusion, POAG in this family does not map to chromosome 1q21-q31 and, thus, they carry a gene that is distinct from the juvenile glaucoma gene.

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

    SciTech Connect

    Thompson, D.B.; Ossowski, V.; Janssen, R.C.; Knowler, W.C.; Bogardus, C.

    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.

  4. The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma

    PubMed Central

    Han, Summer S.; Yeager, Meredith; Moore, Lee E.; Wei, Ming-Hui; Pfeiffer, Ruth; Toure, Ousmane; Purdue, Mark P.; Johansson, Mattias; Scelo, Ghislaine; Chung, Charles C.; Gaborieau, Valerie; Zaridze, David; Schwartz, Kendra; Szeszenia-Dabrowska, Neonilia; Davis, Faith; Bencko, Vladimir; Colt, Joanne S.; Janout, Vladimir; Matveev, Vsevolod; Foretova, Lenka; Mates, Dana; Navratilova, M.; Boffetta, Paolo; Berg, Christine D.; Grubb, Robert L.; Stevens, Victoria L.; Thun, Michael J.; Diver, W. Ryan; Gapstur, Susan M.; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Burdett, Laurie; Brisuda, Antonin; McKay, James D.; Fraumeni, Joseph F.; Chatterjee, Nilanjan; Rosenberg, Philip S.; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Tucker, Margaret A.; Chanock, Stephen J.; Toro, Jorge R.

    2012-01-01

    In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10−8, per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17–1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10−14) and rs12617313 (P = 7.48 × 10−12), both highly correlated with rs9679290 (r2 > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r2 < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10−9, per-allele OR = 1.28, 95% CI: 1.18–1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants. PMID:22113997

  5. Localization of a gene responsible for nonspecific mental retardation (MRX9) to the pericentromeric region of the X chromosome

    SciTech Connect

    Willems, P.; Vits, L.; Buntinx, I.; Raeymaekers, P.; Van Broeckhoven, C.; Ceulemans, B. )

    1993-11-01

    Nonspecific X-linked mental retardation (MRX) includes several distinct entities with mental retardation but without additional distinguishing features. The MRX family reported here has been classified previously as MRX9. In this study, the authors performed linkage analysis of MRX9 with a panel of 43 polymorphic DNA markers dispersed over chromosome X. Two-point linkage analysis revealed lod scores of 3.52 and 3.82 at 0% recombination for OATL1 and MAOA, both located in Xp11.2-p11.4. Lod scores for linkage with PGK1P1, DXS106, and DXS132, all located in Xq11-q13, were 3.83, 3.82, and 3.52, respectively, all at 0% recombination. Multipoint linkage analysis showed two peaks with MAOA and DXS132/DXS106, respectively. Analysis of recombinational events indicated a position of the MRX9 gene between DXS164 and DXS453. These findings are compatible with a location of the MRX9 gene in the pericentromeric region of the X chromosome at Xp21-q13. 26 refs., 3 figs., 2 tabs.

  6. A physically anchored genetic map and linkage to avirulence reveals recombination suppression over the proximal region of Hessian fly chromosome A2.

    PubMed Central

    Behura, Susanta K; Valicente, Fernando H; Rider, S Dean; Shun-Chen, Ming; Jackson, Scott; Stuart, Jeffrey J

    2004-01-01

    Resistance in wheat (Triticum aestivum) to the Hessian fly (Mayetiola destructor), a major insect pest of wheat, is based on a gene-for-gene interaction. Close linkage (3 +/- 2 cM) was discovered between Hessian fly avirulence genes vH3 and vH5. Bulked segregant analysis revealed two DNA markers (28-178 and 23-201) within 10 cM of these loci and only 3 +/- 2 cM apart. However, 28-178 was located in the middle of the short arm of Hessian fly chromosome A2 whereas 23-201 was located in the middle of the long arm of chromosome A2, suggesting the presence of severe recombination suppression over its proximal region. To further test that possibility, an AFLP-based genetic map of the Hessian fly genome was constructed. Fluorescence in situ hybridization of 20 markers on the genetic map to the polytene chromosomes of the Hessian fly indicated good correspondence between the linkage groups and the four Hessian fly chromosomes. The physically anchored genetic map is the first of any gall midge species. The proximal region of mitotic chromosome A2 makes up 30% of its length but corresponded to <3% of the chromosome A2 genetic map. PMID:15166159

  7. A narrow segment of maternal uniparental disomy of chromosome 7q31-qter in Silver-Russell syndrome delimits a candidate gene region.

    PubMed

    Hannula, K; Lipsanen-Nyman, M; Kontiokari, T; Kere, J

    2001-01-01

    Maternal uniparental disomy of chromosome 7 (matUPD7), the inheritance of both chromosomes from only the mother, is observed in approximately 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, gamma2-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 gamma2-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

  8. In vivo footprint analysis and genomic sequencing of the human hypoxanthine-phosphoribosyl transferase (HPRT) 5 prime region on the active and inactive X chromosome

    SciTech Connect

    Hornstra, I.K.; Yang, T.P. )

    1991-03-11

    In female placental mammals, one of the two X chromosome in each somatic cell is randomly inactivated during female embryogenesis as a mechanism for dosage compensation. Once a given X chromosome is inactivated, all mitotic progeny maintain the same X chromosome in the inactive state. DNA-protein interactions and DNA methylation are hypothesized to maintain this allele-specific system of differential gene expression. Ligation-mediated polymerase chain reaction (LMPCR) in vivo footprinting and genomic sequencing were used to study DNA-protein interactions and DNA-methylation within the 5{prime} region of the X-linked human HPRT gene on the active and inactive X chromosomes. In vivo footprint analysis reveals at least one DNA-protein interaction specific to the active HPRT allele in human male fibroblast cells and hamster-human hybrid cells containing only the active human X chromosome. In the region examined, all CpG dinucleotides are methylated on the inactive HPRT allele and unmethylated on the active X allele in hamster-human hybrid cells carrying either the inactive or active human X chromosome, respectively. Thus, DNA-methylation may be mediating the differential binding of sequence-specific DNA-binding proteins to the active or inactive HPRT alleles.

  9. Mapping of the gene encoding the. beta. -amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21

    SciTech Connect

    Patterson, D.; Gardiner, K.; Kao, F.T.; Tanzi, R.; Watkins, P.; Gusella, J.F. )

    1988-11-01

    The gene encoding the {beta}-amyloid precursor protein has been assigned to human chromosome 21, as has a gene responsible for at least some cases of familial Alzheimer disease. Linkage studies strongly suggest that the {beta}-amyloid precursor protein and the product corresponding to familial Alzheimer disease are from two genes, or at least that several million base pairs of DNA separate the markers. The precise location of the {beta}-amyloid precursor protein gene on chromosome 21 has not yet been determined. Here the authors show, by using a somatic-cell/hybrid-cell mapping panel, in situ hybridization, and transverse-alternating-field electrophoresis, that the {beta}-amyloid precursor protein gene is located on chromosome 21 very near the 21q21/21q/22 border and probably within the region of chromosome 21 that, when trisomic, results in Down syndrome.

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

    PubMed Central

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

    2007-01-01

    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. PMID:17921355

  11. Functional analysis of genes implicated in Down syndrome: 1. Cognitive abilities in mice transpolygenic for Down Syndrome Chromosomal Region-1 (DCR-1).

    PubMed

    Chabert, Caroline; Jamon, Marc; Cherfouh, Ameziane; Duquenne, Vincent; Smith, Desmond J; Rubin, Edward; Roubertoux, Pierre L

    2004-11-01

    Down syndrome occurs every 1/1000 births and is the most frequent genetic cause of mental retardation. The genetic substrate of Down syndrome, an extra chromosome 21, was discovered by Lejeune, half-a-century ago, and the chromosome has been fully sequenced, although the gene(s) implicated in the mental retardation observed with the syndrome are still unknown. Observations of patients with partial trisomy of the 21q22.2 fragment suggest that most of the signs of the syndrome, including mental retardation, could be influenced by the region referred to as the Down Minimal Chromosomal Region-1 (DCR-1) for that reason. Using the extensive syntenies between human chromosome 21 and murine chromosome 16, Smith et al. (1995, 1997) developed transpolygenic mice with human chromosome 21 fragments covering the DCR-1. Here, we explored cognitive performances in mice over-expressing the genes carried by these fragments with the Morris water-maze and fear-conditioning procedures. The 152F7 transpolygenic mice had lower performance levels, compared to non-transgenic and other transgenic mice on most measurements in the water-maze. In fear-conditioning, all transgenic mice recorded lower performance levels compared to controls in the altered context stage. The 230E8, 141G6 and 285E6 mice failed to learn or react when the sound used as the conditional stimulus was added. These results showed that the 152F7 region played a crucial role in cognitive impairment, supporting the hypothesis of DYRK-1A gene involvement. However, the data presented here also suggest that other chromosomal regions within the DCR-1 may be involved in specific cognitive functions. PMID:15520513

  12. A distinct region of chromosome 19p13.3 associated with the sporadic form of adenoma malignum of the uterine cervix.

    PubMed

    Lee, J Y; Dong, S M; Kim, H S; Kim, S Y; Na, E Y; Shin, M S; Lee, S H; Park, W S; Kim, K M; Lee, Y S; Jang, J J; Yoo, N J

    1998-03-15

    Adenoma malignum (AM) is known to be one of the malignant tumors that is commonly associated with Peutz-Jeghers syndrome. Recently, the genetic locus of Peutz-Jeghers syndrome was mapped to the telomeric region of chromosome 19p. We analyzed nine sporadic cases of AM with high-density loss of heterozygosity to study the region of chromosome 19p13.2-13.3 using eight microsatellite markers. Our deletion mapping data revealed a distinct region with 100% loss of heterozygosity frequency at marker D19S216. This result indicates that a putative tumor suppressor gene for AM is located at D19S216 on chromosomal band 19p13.3 and plays an important role in AM tumorigenesis. PMID:9515797

  13. Building the repertoire of dispensable chromosome regions in Bacillus subtilis entails major refinement of cognate large-scale metabolic model

    PubMed Central

    Henry, Christopher S.; Zinner, Jenifer F.; Jolivet, Edmond; Cohoon, Matthew P.; Xia, Fangfang; Bidnenko, Vladimir; Ehrlich, S. Dusko; Stevens, Rick L.; Noirot, Philippe

    2013-01-01

    The nonessential regions in bacterial chromosomes are ill-defined due to incomplete functional information. Here, we establish a comprehensive repertoire of the genome regions that are dispensable for growth of Bacillus subtilis in a variety of media conditions. In complex medium, we attempted deletion of 157 individual regions ranging in size from 2 to 159 kb. A total of 146 deletions were successful in complex medium, whereas the remaining regions were subdivided to identify new essential genes (4) and coessential gene sets (7). Overall, our repertoire covers ∼76% of the genome. We screened for viability of mutant strains in rich defined medium and glucose minimal media. Experimental observations were compared with predictions by the iBsu1103 model, revealing discrepancies that led to numerous model changes, including the large-scale application of model reconciliation techniques. We ultimately produced the iBsu1103V2 model and generated predictions of metabolites that could restore the growth of unviable strains. These predictions were experimentally tested and demonstrated to be correct for 27 strains, validating the refinements made to the model. The iBsu1103V2 model has improved considerably at predicting loss of viability, and many insights gained from the model revisions have been integrated into the Model SEED to improve reconstruction of other microbial models. PMID:23109554

  14. The IL-9 receptor gene (IL9R): Genomic structure, chromosomal localization in the pseudoautosomal region of the long arm of sex chromosomes, and identification of IL9R pseudogenes at 9qter, 10pter, 16pter, 18pter

    SciTech Connect

    Kermouni, A.; Godelaine, D.; Lurquin, C.; Szikora, J.P.

    1995-09-20

    Cosmids containing the human IL-9 receptor (R) gene (IL9R) have been isolated from a genomic library using the IL9R cDNA as a probe. We have shown that the human IL9R gene is composed of 11 exons and 10 introns, stretching over {approx} 17 kb, and is located within the pseudoautosomal region of the Xq and Yq chromosome, in the vicinity of the telomere. Analysis of the 5` flanking region revealed multiple transcription initiation sites as well as potential binding motifs for AP1, AP2, AP3, Sp1, and NF-kB, although this region lacks a TATA box. Using the human IL9R cosmid as a probe to perform fluorescence in situ hybridization, additional signals were identified in the subtelomeric regions of chromosomes 9q, 10p, 16p, and 18p. IL9R homologs located on chromosomes 9 and 18 were partially characterized, while those located on chromosomes 16 and 10 were completely sequenced. Although they are similiar to the IL9R gene ({approx} 90% identity), none of these copies encodes a functional receptor: none of them contains sequences homologous to the 5` flanking region or exon 1 of the IL9R gene, and the remaining ORFs have been inactivated by various point mutations and deletions. Taken together, our results indicate that the IL9R gene is located at Xq28 and Yq12, in the long arm pseudoautosomal region, and that four IL9R pseudogenes are located on 9q34, 10p15, 16p13.3 and 18p11.3, probably dispersed as the result of translocations during evolution. 42 refs., 6 figs., 3 tabs.

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

    SciTech Connect

    Wevrick, R.; Kerns, J.A.; Francke, U.

    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.

  16. Three distinct commonly deleted regions of chromosome arm 16q in human primary and metastatic prostate cancers.

    PubMed

    Suzuki, H; Komiya, A; Emi, M; Kuramochi, H; Shiraishi, T; Yatani, R; Shimazaki, J

    1996-12-01

    Human prostate cancers frequently show loss of heterozygosity (LOH) at loci on the long arm of chromosome 16 (16q). In this study, we analyzed prostate cancer specimens from 48 patients (Stage B, 20 cases; Stage C, 10 cases; cancer death, 18 cases) for allelic loss on 16q, using either restriction fragment length polymorphism (RFLP)- or polymerase chain reaction (PCR)-based methods. Allelic losses were observed in 20 (42%) of 48 cases, all of which were informative with at least one locus. Detailed deletion mapping identified three distinct commonly deleted regions on this chromosome arm: q22.1-q22.3, q23.2-q24.1, and q24.3-qter. On the basis of a published sex-averaged framework map, the estimated sizes of the commonly deleted regions were 4.7 (16q22.1-q22.3), 17.2 (16q23.2-q24.1) and 8.4 cM (16q24.3-qter). Allelic losses on 16q were observed more frequently in the cancer-death cases (11 of 18; 61%) than in early-stage tumor cases (9 of 30; 30%; P < 0.05). In 7 of 11 patients from whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 16q, but the metastatic tumors showed LOH. These results suggest that inactivation of tumor suppressor genes on 16q plays an important role in the progression of prostate cancer. We also analyzed exons 5-8 of the E-cadherin gene, located at 16q22.1, in tumor DNA by means of PCR-single strand conformation polymorphism and direct sequencing, but we detected no somatic mutations in this candidate gene. PMID:8946204

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

    PubMed Central

    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. PMID:25738644

  18. Fine structure mapping of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene region of the human X chromosome (Xq26).

    PubMed Central

    Nicklas, J A; Hunter, T C; O'Neill, J P; Albertini, R J

    1991-01-01

    The Xq26-q27 region of the X chromosome is interesting, as an unusually large number of genes and anonymous RFLP probes have been mapped in this area. A number of studies have used classical linkage analysis in families to map this region. Here, we use mutant human T-lymphocyte clones known to be deleted for all or part of the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene, to order anonymous probes known to map to Xq26. Fifty-seven T-cell clones were studied, including 44 derived from in vivo mutation and 13 from in vitro irradiated T-lymphocyte cultures. Twenty anonymous probes (DXS10, DXS11, DXS19, DXS37, DXS42, DXS51, DXS53, DXS59, DXS79, DXS86, DXS92, DXS99, DXS100d, DXS102, DXS107, DXS144, DXS172, DXS174, DXS177, and DNF1) were tested for codeletion with the hprt gene by Southern blotting methods. Five of these probes (DXS10, DXS53, DXS79, DXS86 and DXS177) showed codeletion with hprt in some mutants. The mutants established the following unambiguous ordering of the probes relative to the hprt gene: DXS53-DXS79-5'hprt3'-DXS86-DXS10-DXS177 . The centromere appears to map proximal to DXS53. These mappings order several closely linked but previously unordered probes. In addition, these studies indicate that rather large deletions of the functionally haploid X chromosome can occur while still retaining T-cell viability. Images Figure 1 PMID:1678246

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

    PubMed

    Shaposhnikov, Sergey A; Akopov, Sergey B; Chernov, Igor P; Thomsen, Preben D; Joergensen, Claus; Collins, Andrew R; Frengen, Eirik; Nikolaev, Lev G

    2007-03-01

    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/MARs are located within genes and 36 (90%) in gene introns, of which 15 are in first introns of different genes. The clear tendency of S/MARs from this region to be located within the introns suggests their regulatory role. The S/MAR resource constructed may contribute to an understanding of how the genes in the region are regulated and of how the structural architecture and functional organization of the DNA are related. PMID:17188460

  20. A 4-Mb deletion in the region Xq27.3-q28 is associated with non-random inactivation of the non-mutant X chromosome

    SciTech Connect

    Clarke, J.T.R.; Han, L.P.; Michalickova, K.

    1994-09-01

    A girl with severe Hunter disease was found to have a submicroscopic deletion distrupting the IDS locus in the region Xq27.3-q28 together with non-random inactivation of the non-mutant X chromosome. Southern analysis of DNA from the parents and from hamster-patient somatic cell hybrids containing only the mutant X chromosome revealed that the deletion represented a de novo mutation involving the paternal X chromosome. Methylation-sensitive RFLP analysis of DNA from maternal fibroblasts and lymphocytes showed methylation patterns consistent with random X-inactivation, indicating that the non-random X-inactivation in the patient was not inherited and was likely a direct result of the Xq27.3-q28 deletion. A 15 kb EcoRI junction fragment, identified in patient DNA using IDS cDNA probes, was cloned from a size-selected patient DNA library. Clones containing the deletion junction were restriction mapped and fragments were subcloned and used to isolate normal sequence on either side of the deletion from normal X chromosome libraries. Comparison of the sequences from normal and mutant X chromosome clones straddling the deletion breakpoint showed that the mutation had occurred by recombination between Alu repeats. Screening of YAC contigs containing normal X chromosome sequence from the region of the mutation, using probes from either side of the deletion breakpoint, showed that the deletion was approximately 4 Mb in size. Probing of mutant DNA with 16 STSs distributed throughout the region of the deletion confirmed that the mutation is a simple deletion with no complex rearrangements of islands of retained DNA. A search for sequences at Xq27.3-q28 involved in X chromosome inactivation is in progress.

  1. Recurrent chromosomal aberrations in intravenous leiomyomatosis of the uterus: high-resolution array comparative genomic hybridization study.

    PubMed

    Buza, Natalia; Xu, Fang; Wu, Weiqing; Carr, Ryan J; Li, Peining; Hui, Pei

    2014-09-01

    Uterine intravenous leiomyomatosis (IVL) is a distinct smooth muscle neoplasm with a potential of clinical aggressiveness due to its ability to extend into intrauterine and extrauterine vasculature. In this study, chromosomal alterations analyzed by oligonucleotide array comparative genomic hybridization were performed in 9 cases of IVL. The analysis was informative in all cases with multiple copy number losses and/or gains observed in each tumor. The most frequent recurrent loss of 22q12.3-q13.1 was observed in 6 tumors (66.7%), followed by losses of 22q11.23-q13.31, 1p36.13-p33, 2p25.3-p23.3, and 2q24.2-q32.2 and gains of 6p22.2, 2q37.3 and 10q22.2-q22.3, in decreasing order of frequency. Copy number variants were identified at 14q11.2, 15q11.1-q11.2, and 15q26.2. Genes mapping to the regions of loss include CHEK2, EWS, NF2, PDGFB, and MAP3K7IP1 on chromosome 22q, HEI10 on chromosome 14q, and succinate dehydrogenase subunit B, E2F2, ARID1A KPNA6, EIF3S2 , PTCH2, and PIK3R3 on chromosome 1p. Regional losses on chromosomes 22q and 1p and gains on chromosomes 12q showed overlaps with those previously observed in uterine leiomyosarcomas. In addition, presence of multiple chromosomal aberrations implies a higher level of genetic instability. Follow-up polymerase chain reaction (PCR) sequencing analysis of MED12 gene revealed absence of G> A transition at nucleotides c.130 or c.131 in all 9 cases, a frequent mutation found in uterine leiomyoma and its variants. In conclusion, this is the first report of high-resolution, genome-wide investigation of IVL by oligonucleotide array comparative genomic hybridization. The presence of high frequencies of recurrent regional loss involving several chromosomes is an important finding and likely related to the pathogenesis of the disease. PMID:25033729

  2. Identification and physical localization of useful genes and markers to a major gene-rich region on wheat group 1S chromosomes.

    PubMed Central

    Sandhu, D; Champoux, J A; Bondareva, S N; Gill, K S

    2001-01-01

    The short arm of Triticeae homeologous group 1 chromosomes is known to contain many agronomically important genes. The objectives of this study were to physically localize gene-containing regions of the group 1 short arm, enrich these regions with markers, and study the distribution of genes and recombination. We focused on the major gene-rich region ("1S0.8 region") and identified 75 useful genes along with 93 RFLP markers by comparing 35 different maps of Poaceae species. The RFLP markers were tested by gel blot DNA analysis of wheat group 1 nullisomic-tetrasomic lines, ditelosomic lines, and four single-break deletion lines for chromosome arm 1BS. Seventy-three of the 93 markers mapped to group 1 and detected 91 loci on chromosome 1B. Fifty-one of these markers mapped to two major gene-rich regions physically encompassing 14% of the short arm. Forty-one marker loci mapped to the 1S0.8 region and 10 to 1S0.5 region. Two cDNA markers mapped in the centromeric region and the remaining 24 loci were on the long arm. About 82% of short arm recombination was observed in the 1S0.8 region and 17% in the 1S0.5 region. Less than 1% recombination was observed for the remaining 85% of the physical arm length. PMID:11290727

  3. A yeast artificial chromosome contig that spans the RB1-D13S31 interval on human chromosome 13 and encompasses the frequently deleted region in B-cell chronic lymphocytic leukemia

    SciTech Connect

    Hawthorn, L.; Roberts, T.; Cowell, J.K.

    1995-12-10

    Abnormalities involving chromosome 13 have been a reported as the only cytogenetic change in B-cell chronic lymphocytic leukemia (BCLL). Deletions are the most common cytogenetic abnormality and always involve 13q14, but when translocations are seen, the consistent breakpoint is always in 13q14. It is now established that deletions, distal to the RB1 gene in 13q14, are invariably associated with these translocations. We have recently described the smallest such deletion from a series of rearrangements from these tumors isolated in somatic cell hybrids, which spans approximately 1 Mb. In this report, we present the results of a series of a chromosome walking experiments using YACs and have been able to span this small deletion, which must contain the gene that is frequently deleted in BCLL. Four probes from 13q14 (RB1-mgg15-D13S25-D13S31) were used to isolate corresponding YACs for each of the markers. The chromosomal location of these YACs was verified using FISH, which also demonstrated their nonchimeric nature. Vectorette end rescue was then used to demonstrate the overlap of the YACs and to isolate new clones to complete the contig. The extremes of the contig were shown to cross the chromosome 13 translocation breakpoints isolated in somatic cell hybrids that carry the derivatives of chromosome 13 involved in the smallest BCLL deletion. This YAC contig covers the entire deletion and will prove a valuable resource to begin isolating genes from this region. In addition, we have isolated YACs corresponding to the RB1 locus, which extends the contig over a 3.8-cM distance on the chromosome. 25 refs., 1 fig., 1 tab.

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

    PubMed

    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

    PubMed Central

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

    PubMed

    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. PMID:21730028

  7. A High-Resolution Comparative Chromosome Map of Cricetus cricetus and Peromyscus eremicus Reveals the Involvement of Constitutive Heterochromatin in Breakpoint Regions.

    PubMed

    Vieira-da-Silva, Ana; Louzada, Sandra; Adega, Filomena; Chaves, Raquel

    2015-01-01

    Compared to humans and other mammals, rodent genomes, specifically Muroidea species, underwent intense chromosome reshuffling in which many complex structural rearrangements occurred. This fact makes them preferential animal models for studying the process of karyotype evolution. Here, we present the first combined chromosome comparative maps between 2 Cricetidae species, Cricetus cricetus and Peromyscus eremicus, and the index species Mus musculus and Rattus norvegicus. Comparative chromosome painting was done using mouse and rat paint probes together with in silico analysis from the Ensembl genome browser database. Hereby, evolutionary events (inter- and intrachromosomal rearrangements) that occurred in C. cricetus and P. eremicus since the putative ancestral Muroidea genome could be inferred, and evolutionary breakpoint regions could be detected. A colocalization of constitutive heterochromatin and evolutionary breakpoint regions in each genome was observed. Our results suggest the involvement of constitutive heterochromatin in karyotype restructuring of these species, despite the different levels of conservation of the C. cricetus (derivative) and P. eremicus (conserved) genomes. PMID:25999143

  8. Type 1 diabetes and the control of dexamethazone-induced apoptosis in mice maps to the same region on chromosome 6

    SciTech Connect

    Penha-Goncalves, C.; Leijon, K.; Persson, L.

    1995-08-10

    Quantitative trait loci mapping was used to identify the chromosomal location of genes that contribute to increase the resistance to apoptosis induced in immature CD4{sup +}8{sup +} thymocytes. An F2 intercross of the nonobese diabetic (NOD) mouse (displaying an apoptosis-resistance phenotype) and the C57BL/6 mouse (displaying a nonresistance phenotype) was phenotypically analyzed and genotyped for 32 murine microsatellite polymorphisms. Maximum likelihood methods identified a region on the distal part of chromosome 6 that is linked to dexamethazone-induced apoptosis (lod score = 3.46) and accounts for 14% of the phenotypic variation. This chromosomal region contains the diabetes susceptibility locus Idd6, suggesting that the apoptosis-resistance phenotype constitutes a pathogenesis factor in IDDM of NOD mice. 29 refs., 4 figs.

  9. Long-Read Single Molecule Sequencing to Resolve Tandem Gene Copies: The Mst77Y Region on the Drosophila melanogaster Y Chromosome.

    PubMed

    Krsticevic, Flavia J; Schrago, Carlos G; Carvalho, A Bernardo

    2015-06-01

    The autosomal gene Mst77F of Drosophila melanogaster is essential for male fertility. In 2010, Krsticevic et al. (Genetics 184: 295-307) found 18 Y-linked copies of Mst77F ("Mst77Y"), which collectively account for 20% of the functional Mst77F-like mRNA. The Mst77Y genes were severely misassembled in the then-available genome assembly and were identified by cloning and sequencing polymerase chain reaction products. The genomic structure of the Mst77Y region and the possible existence of additional copies remained unknown. The recent publication of two long-read assemblies of D. melanogaster prompted us to reinvestigate this challenging region of the Y chromosome. We found that the Illumina Synthetic Long Reads assembly failed in the Mst77Y region, most likely because of its tandem duplication structure. The PacBio MHAP assembly of the Mst77Y region seems to be very accurate, as revealed by comparisons with the previously found Mst77Y genes, a bacterial artificial chromosome sequence, and Illumina reads of the same strain. We found that the Mst77Y region spans 96 kb and originated from a 3.4-kb transposition from chromosome 3L to the Y chromosome, followed by tandem duplications inside the Y chromosome and invasion of transposable elements, which account for 48% of its length. Twelve of the 18 Mst77Y genes found in 2010 were confirmed in the PacBio assembly, the remaining six being polymerase chain reaction-induced artifacts. There are several identical copies of some Mst77Y genes, coincidentally bringing the total copy number to 18. Besides providing a detailed picture of the Mst77Y region, our results highlight the utility of PacBio technology in assembling difficult genomic regions such as tandemly repeated genes. PMID:25858959

  10. Long-Read Single Molecule Sequencing to Resolve Tandem Gene Copies: The Mst77Y Region on the Drosophila melanogaster Y Chromosome

    PubMed Central

    Krsticevic, Flavia J.; Schrago, Carlos G.; Carvalho, A. Bernardo

    2015-01-01

    The autosomal gene Mst77F of Drosophila melanogaster is essential for male fertility. In 2010, Krsticevic et al. (Genetics 184: 295−307) found 18 Y-linked copies of Mst77F (“Mst77Y”), which collectively account for 20% of the functional Mst77F-like mRNA. The Mst77Y genes were severely misassembled in the then-available genome assembly and were identified by cloning and sequencing polymerase chain reaction products. The genomic structure of the Mst77Y region and the possible existence of additional copies remained unknown. The recent publication of two long-read assemblies of D. melanogaster prompted us to reinvestigate this challenging region of the Y chromosome. We found that the Illumina Synthetic Long Reads assembly failed in the Mst77Y region, most likely because of its tandem duplication structure. The PacBio MHAP assembly of the Mst77Y region seems to be very accurate, as revealed by comparisons with the previously found Mst77Y genes, a bacterial artificial chromosome sequence, and Illumina reads of the same strain. We found that the Mst77Y region spans 96 kb and originated from a 3.4-kb transposition from chromosome 3L to the Y chromosome, followed by tandem duplications inside the Y chromosome and invasion of transposable elements, which account for 48% of its length. Twelve of the 18 Mst77Y genes found in 2010 were confirmed in the PacBio assembly, the remaining six being polymerase chain reaction−induced artifacts. There are several identical copies of some Mst77Y genes, coincidentally bringing the total copy number to 18. Besides providing a detailed picture of the Mst77Y region, our results highlight the utility of PacBio technology in assembling difficult genomic regions such as tandemly repeated genes. PMID:25858959

  11. High frequency of allelic imbalance at chromosome region 16q22-23 in human breast cancer: correlation with high PgR and low S phase.

    PubMed

    Skirnisdottir, S; Eiriksdottir, G; Baldursson, T; Barkardottir, R B; Egilsson, V; Ingvarrson, S

    1995-04-21

    The loss of genetic material from a specific chromosome region in tumors suggests that presence of tumor-suppressor genes. Loss of heterozygosity (LOH) or allelic imbalance (AI) on the long arm of chromosome 16 is a known event in sporadic breast cancer. To locate the commonly deleted regions, and therefore (a) candidate tumor-suppressor gene(s), a deletion map of chromosome 16 was made, using 10 microsatellite markers on 150 sporadic breast tumors. The 3 smallest regions of overlap (SRO) were detected on the long arm of chromosome 16. Allelic imbalance was observed with at least one marker in 67% of the tumors. One marker, D16S421, at the 16q22-23 region, showed the highest allelic imbalance, 58%. Tumors with and without AI on 16q were tested for correlation with clinico-pathological features of the tumors such as estrogen- and progesterone-receptor content (ER and PgR), age at diagnosis, tumor size, node status, histological type, S-phase fraction, AI on chromosome 3p, and ploidy. A correlation was found between AI on 16q and high PgR content, also low S-phase fraction (99% confidence limits). A comparison of tumors with and without AI at the D16S421 marker locus revealed a slight correlation with high PgR content. The survival data showed no difference between patients with AI on 16q and those with a normal allele pattern on the long arm of chromosome 16. PMID:7615353

  12. High-resolution physical mapping of a 250-kb region of human chromosome 11q24 by genomic sequence sampling (GSS)

    SciTech Connect

    Selleri, L.; Smith, M.W.; Holmsen, A.L.

    1995-04-10

    A physical map of the region of human chromosome 11q24 containing the FLI1 gene, disrupted by the t(11;22) translocation in Ewing sarcoma and primitive neuroectodermal tumors, was analyzed by genomic sequence sampling. Using a 4- to 5-fold coverage chromosome 11-specific library, 22 region-specific cosmid clones were identified by phenol emulsion reassociation hybridization, with a 245-kb yeast artificial chromosome clone containing the FLI1 gene, and by directed {open_quotes}walking{close_quotes} techniques. Cosmid contigs were constructed by individual clone fingerprinting using restriction enzyme digestion and assembly with the Genome Reconstruction and AsseMbly (GRAM) computer algorithm. The relative orientation and spacing of cosmid contigs with respect to the chromosome were determined by the structural analysis of cosmid clones and by direct visual in situ hybridization mapping. Each cosmid clone in the contig was subjected to {open_quotes}one-pass{close_quotes} end sequencing, and the resulting ordered sequence fragments represent {approximately}5% of the complete DNA sequence, making the entire region accessible by PCR amplification. The sequence samples were analyzed for putative exons, repetitive DNAs, and simple sequence repeats using a variety of computer algorithms. Based upon the computer predictions, Southern and Northern blot experiments led to the independent identification and localization of the FLI1 gene as well as a previously unknown gene located in this region of chromosome 11q24. This approach to high-resolution physical analysis of human chromosomes allows the assembly of detailed sequence-based maps. 62 refs., 7 figs.

  13. A gene responsible for profound congenital nonsyndromal recessive deafness maps to the pericentromeric region of chromosome 17

    SciTech Connect

    Friedman, T.B.; Liang, Y.; Asher, J.H. Jr.

    1994-09-01

    Autosomal recessive deafness is the most common form of human hereditary hearing loss. Two percent of the 2,185 residents of Bengkala, Bali, Indonesia have profound congenital neurosensory nonsyndromal hereditary deafness due to a fully penetrant autosomal recessive mutation (NARD1). Families, identified through children with profound congenital deafness having hearing parents, give the expected 25% deaf progeny when corrected for ascertainment bias. Congenitally deaf individuals from Bengkala show no response to pure tone audiological examination. Obligate heterozygotes for autosomal recessive deafness in Bengkala have normal or borderline normal hearing. A chromosomal location for NARD1 was assigned directly using a linkage strategy that combines allele-frequency dependent homozygosity mapping (AHM) followed by an analysis of historical recombinants to position NARD1 relative to flanking markers. Thirteen deaf Bengkala villagers of hearing parents were typed initially for 148 STRPs distributed across the human genome and a cluster of tightly linked 17p markers with a significantly higher number of homozygotes than expected under Hardy-Weinberg and linkage equilibrium were identified. NARD1 maps closest to STRPs for D17S261 (Mfd41) and D17S805 (AFM234ta1) that are 3.2 cM apart. Recombinant genotypes for the flanking markers, D17S122 (VAW409) and D17S783 (AFM026vh7), in individuals homozygous for NARD1 place NARD1 in a 5.3 cM interval of the pericentromeric region of chromosome 17 on a refined 17p-17q12 genetic map.

  14. High-density genetic map of the BRCA1 region of chromosome 17q12-q21

    SciTech Connect

    Anderson, L.A.; Friedman, L.; Lynch, E.; King, M.C. ); Osborne-Lawrence, S.; Bowcock, A. ); Weissenbach, J. )

    1993-09-01

    To facilitate the positional cloning of the breast-ovarian cancer gene BRCA1, the authors constructed a high-density genetic map of the 8.3-cM interval between D17S250 and GIP on chromosome 17q12-q21. Markers were mapped by linkage in the CEPH and in extended kindreds in the breast cancer series. The map comprises 33 ordered polymorphisms, including 12 genes and 21 anonymous markers, yielding an average of one polymorphism every 250 kb. Twenty-five of the markers are PCR-based systems. The order of polymorphic genes and markers is cen-D17S250-D17S518-HER2-THRA1-RARA-D17S80-KRT10-[D17S800-D17S857]-GAS-D17S856-EDH17B-D17S855-D17S859-D17S858-[PPY-D17S78]-D17S183-EPB3-D17S579-D17S509-[D17S508-D17S190 = D17S810]-D17S791-[D17S181 = D17S806]-D17S797-HOX2B-GP3A-[D17S507 = GIP]-qter. BRCA1 lies in the middle of the interval, between THRA1 and D17S183. Markers from this map can be used to determine whether cancer is linked to BRCA1 in families, to evaluate whether tumors have lost heterozygosity at loci in the region, and to identify probes for characterizing chromosomal rearrangements from patients and from tumors. 21 refs., 1 fig., 3 tabs.

  15. DNA sequence variation in a non-coding region of low recombination on the human X chromosome.

    PubMed

    Kaessmann, H; Heissig, F; von Haeseler, A; Pääbo, S

    1999-05-01

    DNA sequence variation has become a major source of insight regarding the origin and history of our species as well as an important tool for the identification of allelic variants associated with disease. Comparative sequencing of DNA has to date focused mainly on mitochondrial (mt) DNA, which due to its apparent lack of recombination and high evolutionary rate lends itself well to the study of human evolution. These advantages also entail limitations. For example, the high mutation rate of mtDNA results in multiple substitutions that make phylogenetic analysis difficult and, because mtDNA is maternally inherited, it reflects only the history of females. For the history of males, the non-recombining part of the paternally inherited Y chromosome can be studied. The extent of variation on the Y chromosome is so low that variation at particular sites known to be polymorphic rather than entire sequences are typically determined. It is currently unclear how some forms of analysis (such as the coalescent) should be applied to such data. Furthermore, the lack of recombination means that selection at any locus affects all 59 Mb of DNA. To gauge the extent and pattern of point substitutional variation in non-coding parts of the human genome, we have sequenced 10 kb of non-coding DNA in a region of low recombination at Xq13.3. Analysis of this sequence in 69 individuals representing all major linguistic groups reveals the highest overall diversity in Africa, whereas deep divergences also exist in Asia. The time elapsed since the most recent common ancestor (MRCA) is 535,000+/-119,000 years. We expect this type of nuclear locus to provide more answers about the genetic origin and history of humans. PMID:10319866

  16. The telomeric region of the human X chromosome long arm: presence of a highly polymorphic DNA marker and analysis of recombination frequency.

    PubMed Central

    Oberlé, I; Drayna, D; Camerino, G; White, R; Mandel, J L

    1985-01-01

    A DNA fragment (named St14) derived from the human X chromosome reveals a small family of related sequences that have been mapped to the Xq26-Xq28 region by using a panel of rodent-human somatic cell hybrids. The probe detects in human DNA digested by Taq I a polymorphic system defined by a series of at least eight allelic fragments with a calculated heterozygosity in females of 80%. With Msp I, we found three additional restriction fragment length polymorphisms, each of them being defined by two alleles. These polymorphisms are also common in Caucasian populations. The genetic locus defined by probe St14 has been localized more precisely to the distal end of the X chromosome (in band q28) by linkage analysis to other polymorphic DNA markers. The results obtained suggest that the frequency of recombination is distributed very unevenly in the q27-qter region of the X chromosome, with a cluster of seven tightly linked loci in q28 showing about 30% recombination with the gene for coagulation factor IX located in the neighboring q27 band. Probe St14 reveals one of the most polymorphic loci known to date in the human genome, and 17 different genotypes have already been observed. It constitutes the best marker on the X chromosome and should be of great use for the genetic study of three important diseases: hemophilia A, mental retardation with a fragile X chromosome, and adrenoleukodystrophy. Images PMID:2986139

  17. Genomic Anatomy of a Premier Major Histocompatibility Complex Paralogous Region on Chromosome 1q21–q22

    PubMed Central

    Shiina, Takashi; Ando, Asako; Suto, Yumiko; Kasai, Fumio; Shigenari, Atsuko; Takishima, Nobusada; Kikkawa, Eri; Iwata, Kyoko; Kuwano, Yuko; Kitamura, Yuka; Matsuzawa, Yumiko; Sano, Kazumi; Nogami, Masahiro; Kawata, Hisako; Li, Suyun; Fukuzumi, Yasuhito; Yamazaki, Masaaki; Tashiro, Hiroyuki; Tamiya, Gen; Kohda, Atsushi; Okumura, Katsuzumi; Ikemura, Toshimichi; Soeda, Eiichi; Mizuki, Nobuhisa; Kimura, Minoru; Bahram, Seiamak; Inoko, Hidetoshi

    2001-01-01

    Human chromosomes 1q21–q25, 6p21.3–22.2, 9q33–q34, and 19p13.1–p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21–25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21–q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides. [The nucleotide sequence data reported in this paper have been submitted to the DDBJ, EMBL, and GenBank databases under

  18. Identification and mapping of ten new potential insulators in the FXYD5-COX7A1 region of human chromosome 19q13.12.

    PubMed

    Didych, D A; Akopov, S B; Snezhkov, E V; Skaptsova, N V; Nikolaev, L G; Sverdlov, E D

    2009-07-01

    A positive-negative selection system revealed 10 potential insulators able to block enhancer interaction with promoter in the 10(6) bp human chromosome 19 region between genes FXYD5 and COX7A1. Relative positions of insulators and genes are in accord with the hypothesis that insulators subdivide genomic DNA into independently regulated loop domains. PMID:19747092

  19. Genome-wide linkage analysis to identify chromosomal regions affecting phenotypic traits in the chicken. I. Growth and average daily gain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A genome scan was used to detect chromosomal regions and QTL that control quantitative traits of economic importance in chickens. Two unique F2 crosses generated from a commercial broiler male line and 2 genetically distinct inbred lines (Leghorn and Fayoumi) were used to identify QTL affecting BW a...

  20. Presentation of 17 Y-chromosomal STRs in the population of the Sverdlovsk region.

    PubMed

    Trynova, Elena G; Tsitovich, Tamara N; Vylegzhanina, Elena Ya; Bandurenko, Natalija A; Parson, Walther

    2011-06-01

    We established a data set of 17 Y-STRs (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS438, DYS439, DYS437, DYS448, DYS456, DYS458, DYS635 and Y-GATA-H4) of 832 unrelated males from the Sverdlovsk region, Russian Federation. In total we observed 773 different haplotypes of which 732 were unique and 41 occurred between two and nine times in the investigated population. The haplotype diversity was 0.9981 and the discrimination capacity was 0.9291. This study represents the Y-STR reference data set for forensic applications in the Sverdlovsk region. PMID:21277273

  1. Isolation of cDNAs from the spinal muscular atrophy gene region with yeast artificial chromosomes

    SciTech Connect

    Deng, H.X.; He, X.X.; Hung, W.Y.

    1994-09-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of anterior horn cells, leading to progressive paralysis of voluntary muscles. The SMA gene(s) is located at 5q11.2-q13.3, between D5S435 and D5S112. To isolate potential candidate gene(s) responsible for SMA, we used the YACs within the SMA gene region as probes to screen a human brainstem cDNA library. Thirteen cDNA clones were isolated. Their sizes range from 0.7 kb to 5 kb. Seven clones were found to be unique in sequence; the remaining six clones contain repetitive sequences. Five out of these seven unique clones have been used as probes to screen a phage genomic DNA library. Phage genomic clones isolated with individual unique cDNA were used for fluorescence in situ hybridization to identify the origin of cDNAs. These five unique sequences are all located in the 5q13 region, indicating the reliability of our screening method. All the thirteen clones have been partially sequenced (about 300 bp) from each end. No homology has been found with any known EST or known genes. No cross hybridization was detected among the unique clones, suggesting that there may be distinct new genes encoded in this region.

  2. Deletion of a telomeric region on chromosome 8 correlates with higher productivity and stability of CHO cell lines.

    PubMed

    Ritter, Anett; Voedisch, Bernd; Wienberg, Johannes; Wilms, Burkhard; Geisse, Sabine; Jostock, Thomas; Laux, Holger

    2016-05-01

    Chinese Hamster Ovary (CHO) cells are widely used for large scale production of recombinant biopharmaceuticals. Although these cells have been extensively used, a demand to further increase the performance, for example, to facilitate the process of clone selection to isolate the highest producing cell lines that maintain stability of production over time is still existing. We compared gene expression profiles of high versus low producing CHO clones to identify regulated genes which can be used as biomarkers during clone selection or for cell line engineering. We present evidence that increased production rates and cell line stability are correlated with the loss of the telomeric region of the chromosome 8. A new parental CHO cell line lacking this region was generated and its capability for protein production was assessed. The average volumetric productivity of cells after gene transfer and selection was found to be several fold improved, facilitating the supply of early drug substance material to determine for example, quality. In addition, significantly more cell clones with a higher average productivity and higher protein production stability were obtained with the new host cell line after single cell cloning. This allows reduced efforts in single cell sorting, screening of fewer clones and raises the opportunity to circumvent time and labor-intensive stability studies. Biotechnol. Bioeng. 2016;113: 1084-1093. © 2015 Wiley Periodicals, Inc. PMID:26523402

  3. Adrenocorticotropin receptor/melanocortin receptor-2 maps within a reported susceptibility region for bipolar illness on chromosome 18

    SciTech Connect

    Detera-Wadleigh, S.D.; Yoon, Sung W.; Goldin, L.R.

    1995-08-14

    We have examined the possible linkage of adrenocorticotropin receptor/melanocortin receptor-2 (ACTHR/MC-2) to a reported putative susceptibility locus for bipolar illness (BP) in 20 affected pedigrees. Initially, allelic variants of the gene were identified by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) and the gene was genetically mapped using both the Centre d`Etudes du Polymorphisme Humain (CEPH) pedigrees and the BP pedigrees used in this study. We found that the ACTHR/MC-2 gene maps between D18S53 and D18S66. These loci span a region of chromosome 18 which, in a previous study revealed a putative predisposing locus to BP through nonparametric methods of analyses, although affected sib-pair (ASP) method revealed an increase in allele sharing among ill individuals, P=0.023. Since this receptor is within a potential linkage region, ACTHR/MC-2 could be considered a candidate gene for BP. 22 refs., 4 figs., 2 tabs.

  4. Congenital fibrosis of the extraocular muscles maps to the centromeric region of human chromosome 12 in multiple families

    SciTech Connect

    Engle, E.C.; Kunkel, L.M.; Beggs, A.H.

    1994-09-01

    Congenital fibrosis of the extraocular muscles (CFEOM) is an autosomal dominant, ocular disorder characterized by congenital, non-progressive bilateral ptosis and external ophthalmoplegia with a compensatory backward tilt of the head. The pathophysiology of this disorder is unknown and it is unclear if it has a primary neurogenic or myopathic etiology. Postmortem examination of one affected individual reveals normal brainstem, cranial nerves, and non-fibrotic extraocular muscle (EOM). EOM biopsies of several other affected individuals contain relatively normal fibers interspersed in connective tissue, possibly representing normal tendinous insertions. We recently reported linkage of this disease in two unrelated families to markers in the centromeric region of human chromosome 12. D12S59 did not recombine with the disease giving a two-point lod score of 12.5 ({theta}=0.00) while D12S87 and D12S85 flank the CFEOM locus with two-point lod scores of 8.9 ({theta}=0.03) and 5.4 ({theta}=0.03), respectively. Recent experiments with two additional families indicate that the disease in all four kindreds maps to the same locus. The use of several new markers has allowed us to identify a new flanking marker (CHLC, GATA5A09) reducing the size of the critical region to approximately 3.7 cM. Furthermore, D12S331 and D12S345 are nonrecombinant and apparently within the interval D12S87-GATA5A09.

  5. A 11 Mb YAC-based contig spanning the familial juvenile nephronophthisis region (NPH1) located on chromosome 2q

    SciTech Connect

    Konrad, M.; Saunier, S.; Silbermann, F.

    1995-12-10

    A gene (NPH1) responsible for approximately 90% of the purely renal form of familial juvenile nephronophthisis, a progressive tubulo-interstitial kidney disorder, maps to human chromosome 2. We report the construction of a YAC-based contig spanning the critical NPH1 region and the flanking genetic markers. This physical map was integrated with a refined genetic map that restricted the NPH1 interval to about 2 cM; this interval corresponds to a maximum physical distance of 3.5 Mb. The entire contig covers 9 cM between the loci D2S135 and D2S121. The maximum physical distance between these two markers is approximately 11.3 Mb. Forty-five sequence-tagged sites, including six genes, have been located within this contig. PAX8, a member of the human paired box gene family, that is expressed in the developing kidney, was assigned outside the restricted NPH1 critical region and cannot therefore be regarded as a candidate gene. This set of overlapping clones represents a useful resource for further targeted development of genetic markers and for the characterization of candidate genes responsible for juvenile nephronophthisis. 26 refs., 2 figs., 3 tabs.

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

    SciTech Connect

    Duggirala, R.; Stern, M.P.; Reinhart, L.J.

    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.

  7. Towards the cloning of imprinted genes in the Prader-Willi/Angelman region of chromosome 15q11-q13

    SciTech Connect

    Nakao, M.; Sutcliffe, J.S.; Beaudet, A.L.

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct clinical phenotypes resulting from paternal and maternal deficiencies respectively in human chromosome 15q11-q13. The data suggest the presence of oppositely imprinted genes in the region, and the gene for small nuclear ribonucleoprotein-associated polypeptide N (SNRPN) has been identified as a candidate gene for PWS. Previous strategies for positional cloning identified a number of transcripts from the PWS/AS region, and two of them, PAR-5 (D15S226E) and PAR-1 (D15S227E), are paternally expressed in cultured human cells from patients deleted for 15q11-q13 as is SNRPN. Cosmid contig maps have been developed from the following YACs (contained loci in parentheses): 307A12 (D15S13), 457B4 (SNRPN), 132D4 (D15S10), A229A2, and 378A12 (D15S113), to facilitate molecular studies of PWS and AS. Exon trapping has been employed to isolate putative exons from these overlapping cosmids. Two trapped fragments from the D15S113 region and one fragment from the SNRPN region has been isolated. Sequence information is available for all of the fragments. In addition to imprinting analysis in cultured human cells, we have developed a method to detect imprinting in mouse and human using a GC-clamped denaturing gradient gel electrophoresis strategy, in combination with reverse transcription-polymerase chain reaction. The imprinting analyses of putative exons are in progress to investigate their possible candidacy for involvement in PWS or AS phenotypes.

  8. The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers

    PubMed Central

    Yao, Baojin; Wang, Qiuqing; Liu, Chia-Feng; Bhattaram, Pallavi; Li, Wei; Mead, Timothy J.; Crish, James F.; Lefebvre, Véronique

    2015-01-01

    Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized skeleton malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –­350/–50-kb region 5′ of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at –250 kb) confines its activity to condensed prechondrocytes, E195 mainly targets proliferating chondrocytes, and E84 is potent in all differentiated chondrocytes. E84 and E195 synergize with E70, previously shown to be active in most Sox9-expressing somatic tissues, including cartilage. While SOX9 protein powerfully activates E70, it does not control E250. It requires its SOX5/SOX6 chondrogenic partners to robustly activate E195 and additional factors to activate E84. Altogether, these results indicate that SOX9 expression in chondrocytes relies on widely spread transcriptional modules whose synergistic and overlapping activities are driven by SOX9, SOX5/SOX6 and other factors. They help elucidate mechanisms underlying campomelic dysplasia and will likely help uncover other disease mechanisms. PMID:25940622

  9. Chromosomal Conditions

    MedlinePlus

    ... 150 babies is born with a chromosomal condition. Down syndrome is an example of a chromosomal condition. Because ... all pregnant women be offered prenatal tests for Down syndrome and other chromosomal conditions. A screening test is ...

  10. Mapping of the gene for the p60 subunit of the human chromatin assembly factor (CAF1A) to the Down syndrome region of chromosome 21

    SciTech Connect

    Blouin, J.L.; Gos, A.; Morris, M.A.; Antonarakis, S.E.

    1996-04-15

    Exon trapping was used to clone portions of genes from the Down syndrome critical region (DSCR) of human chromosome 21. One trapped sequence showed complete homology with nucleotide sequence U20980 (GenBank), which corresponds to the gene for the p60 subunit of the human chromatin assembly factor-1 (CAF1A). We mapped this gene to human chromosome 21 by fluorescence in situ hybridization, by the use of somatic cell hybrids, and by hybridization to chromosome 21-specific YACs and cosmids. The CAF1A gene localizes to YACs 745H11 and 230E8 of the Chumakov et al. YAC contig, within the DSCR on 21q22. This CAF1A, which belongs to the WD-motif family of genes and interacts with other polypeptide subunits to promote assembly of histones to replicating DNA, may contribute in a gene dosage-dependent manner to the phenotype of Down syndrome. 22 refs., 1 fig.

  11. Further localization of X-linked hydrocephalus in the chromosomal region Xq28

    PubMed Central

    Willems, Patrick J.; Vits, Lieve; Raeymaekers, Peter; Beuten, Joke; Coucke, Paul; Holden, Jeanette J. A.; Van Broeckhoven, Christine; Warren, Stephen T.; Sagi, Michal; Robinson, David; Dennis, Nick; Friedman, Kenneth J.; Magnay, Dorothy; Lyonnet, Stanislas; White, Bradley N.; Wittwer, Bärbel H.; Aylsworth, Arthur S.; Reicke, Sigrid

    1992-01-01

    X-linked hydrocephalus (HSAS) is the most frequent genetic form of hydrocephalus. Clinical symptoms of HSAS include hydrocephalus, mental retardation, clasped thumbs, and spastic paraparesis. Recently we have assigned the HSAS gene to Xq28 by linkage analysis. In the present study we used a panel of 18 Xq27-q28 marker loci to further localize the HSAS gene in 13 HSAS families of different ethnic origins. Among the Xq27-q28 marker loci used, DXS52, DXS15, and F8C gave the highest combined lod scores, of 14.64, 6.53 and 6.33, respectively, at recombination fractions of .04, 0, and .05, respectively. Multipoint linkage analysis localizes the HSAS gene in the telomeric part of the Xq28 region, with a maximal lod score of 20.91 at 0.5 cM distal to DXS52. Several recombinations between the HSAS gene and the Xq28 markers DXS455, DXS304, DXS305, and DXS52 confirm that the HSAS locus is distal to DXS52. One crossover between HSAS and F8C suggests the HSAS gene to be proximal to F8C. Therefore, data from multipoint linkage analysis and the localization of key crossovers indicate that the HSAS gene is most likely located between DXS52 and F8C. This high-resolution genetic mapping places the HSAS locus within a region of <2 Mb in length, which is now amenable to positional cloning. ImagesFigure 2Figure 3 PMID:1642232

  12. Association of ADHD and the Protogenin gene in the chromosome 15q21.3 reading disabilities linkage region.

    PubMed

    Wigg, K G; Feng, Y; Crosbie, J; Tannock, R; Kennedy, J L; Ickowicz, A; Malone, M; Schachar, R; Barr, C L

    2008-11-01

    Twin studies indicate genetic overlap between symptoms of attention deficit hyperactivity disorder (ADHD) and reading disabilities (RD), and linkage studies identify several chromosomal regions possibly containing common susceptibility genes, including the 15q region. Based on a translocation finding and association to two specific alleles, the candidate gene, DYX1C1, has been proposed as the susceptibility gene for RD in 15q. Previously, we tested markers in DYX1C1 for association with ADHD. Although we identified association for haplotypes across the gene, we were unable to replicate the association to the specific alleles reported. Thus, the risk alleles for ADHD are yet to be identified. The susceptibility alleles may be in a remote regulatory element, or DYX1C1 may not be the risk gene. To continue study of 15q, we tested a coding region change in DYX1C1, followed by markers across the gene Protogenin (PRTG) in 253 ADHD nuclear families. PRTG was chosen based on its location and because it is closely related to DCC and Neogenin, two genes known to guide migratory cells and axons during development. The markers in DYX1C1 were not associated to ADHD when analyzed individually; however, six markers in PRTG showed significant association with ADHD as a categorical trait (P = 0.025-0.005). Haplotypes in both genes showed evidence for association. We identified association with ADHD symptoms measured as quantitative traits in PRTG, but no evidence for association with two key components of reading, word identification and decoding was observed. These findings, while preliminary, identify association of ADHD to a gene that potentially plays a role in cell migration and axon growth. PMID:19076634

  13. Fine structure mapping of a gene-rich region of wheat carrying Ph1, a suppressor of crossing over between homoeologous chromosomes

    PubMed Central

    Sidhu, Gaganpreet K.; Rustgi, Sachin; Shafqat, Mustafa N.; von Wettstein, Diter; Gill, Kulvinder S.

    2008-01-01

    The wheat gene-rich region (GRR) 5L0.5 contains many important genes, including Ph1, the principal regulator of chromosome pairing. Comparative marker analysis identified 32 genes for the GRR controlling important agronomic traits. Detailed characterization of this region was accomplished by first physically localizing 213 wheat group 5L-specific markers, using group 5 nulli-tetrasomics, three Ph1 gene deletion/insertion mutants, and nine terminal deletion lines with their breakpoints around the 5L0.5 region. The Ph1 gene was localized to a much smaller region within the GRR (Ph1 gene region). Of the 61 markers that mapped in the four subregions of the GRR, 9 mapped in the Ph1 gene region. High stringency sequence comparison (e < 1 ×10−25) of 157 group 5L-specific wheat ESTs identified orthologs for 80% sequences in rice and 71% in Arabidopsis. Rice orthologs were present on all rice chromosomes, although most (34%) were on rice chromosome 9 (R9). No single collinear region was identified in Arabidopsis even for a smaller region, such as the Ph1 gene region. Seven of the nine Ph1 gene region markers mapped within a 450-kb region on R9 with the same gene order. Detailed domain/motif analysis of the 91 putative genes present in the 450-kb region identified 26 candidates for the Ph1 gene, including genes involved in chromatin reorganization, microtubule attachment, acetyltransferases, methyltransferases, DNA binding, and meiosis/anther specific proteins. Five of these genes shared common domains/motifs with the meiosis specific genes Zip1, Scp1, Cor1, RAD50, RAD51, and RAD57. Wheat and Arabidopsis homologs for these rice genes were identified. PMID:18398005

  14. Human dopamine {beta}-hydroxylase locus and the chromosome 9q34 region in alcoholism

    SciTech Connect

    Parsian. A.; Suarez, B.K.; Hampe, C.

    1994-09-01

    Human dopamine {beta}-hydroxylase (DBH) is responsible for conversion of dopamine to norepinephrine in catecholamine neurons. Potential inhibitors of this enzyme do exist, but they are generally not effective in vivo in reducing tissue concentrations of catecholamines. The gene for DBH has been localized to 9q34 by linkage analysis and in situ hybridization. Recently there have been reports indicating a suggestive evidence of linkage between DNA markers in 9q34 region and alcoholism. In order to test for this suggestive linkage, we have genotyped a sample of 134 subjects with alcoholism, 30 alcoholic families (n=302) and 92 normal controls. The alcoholic subjects are probands of multiple incidence families. The normal controls are an epidemiologically ascertained samples of middle-aged, unrelated individuals. The two groups were matched for sex and ethnic background. The markers used in this study were dinucleotide repeats in the DBH gene, and two highly informative (CA) markers (D9S64, D9S66) flanking the DBH gene. A preliminary affected-sib-pair analysis was carried out under two diagnostic schemes. Regardless of whether `probable` alcoholics are classified as unaffected (t=0.63) or affected (t=1.50), these data do not reveal a significant excess in DBH marker sharing among affected-sib-pairs. However, the comparison of the DBH marker allele frequencies between the unrelated alcoholic panel and the unrelated normal control panel was significant at the p=0.04 level.

  15. Characterization of the promoter region of the gene for the rat neutral and basic amino acid transporter and chromosomal localization of the human gene.

    PubMed Central

    Yan, N; Mosckovitz, R; Gerber, L D; Mathew, S; Murty, V V; Tate, S S; Udenfriend, S

    1994-01-01

    The promoter region of the rat kidney neutral and basic amino acid transporter (NBAT) gene has been isolated and sequenced. The major transcription initiation site was mapped by primer extension. The entire promoter region and a set of 5' deletions within it were expressed at a high level in LLC-PK1 cells using the luciferase indicator gene. Positive and negative regulatory elements in the promoter region were observed. A human genomic clone of the transporter was also obtained and was used to localize the NBAT gene at the p21 region of chromosome 2. Images PMID:8052618

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

    SciTech Connect

    Fennelly, J.; Laval, S.; Wright, E.; Plumb, M.

    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.

  17. The H19 Imprinting Control Region Mediates Preimplantation Imprinted Methylation of Nearby Sequences in Yeast Artificial Chromosome Transgenic Mice

    PubMed Central

    Okamura, Eiichi; Matsuzaki, Hitomi; Sakaguchi, Ryuuta; Takahashi, Takuya; Fukamizu, Akiyoshi

    2013-01-01

    In the mouse Igf2/H19 imprinted locus, differential methylation of the imprinting control region (H19 ICR) is established during spermatogenesis and is maintained in offspring throughout development. Previously, however, we observed that the paternal H19 ICR, when analyzed in yeast artificial chromosome transgenic mice (YAC-TgM), was preferentially methylated only after fertilization. To identify the DNA sequences that confer methylation imprinting, we divided the H19 ICR into two fragments (1.7 and 1.2 kb), ligated them to both ends of a λ DNA fragment into which CTCF binding sites had been inserted, and analyzed this in YAC-TgM. The maternally inherited λ sequence, normally methylated after implantation in the absence of H19 ICR sequences, became hypomethylated, demonstrating protective activity against methylation within the ICR. Meanwhile, the paternally inherited λ sequence was hypermethylated before implantation only when a 1.7-kb fragment was ligated. Consistently, when two subfragments of the H19 ICR were individually investigated for their activities in YAC-TgM, only the 1.7-kb fragment was capable of introducing paternal allele-specific DNA methylation. These results show that postfertilization methylation imprinting is conferred by a paternal allele-specific methylation activity present in a 1.7-kb DNA fragment of the H19 ICR, while maternal allele-specific activities protect the allele from de novo DNA methylation. PMID:23230275

  18. Receptor protein-tyrosine phosphatase. gamma. is a candidate tumor suppressor gene at human chromosome region 3p21

    SciTech Connect

    LaForgia, S.; Cannizzaro, L.A.; Boghosian-Sell, L.; Croce, C.M.; Huebner, K. ); Morse, B. ); Levy, J.; Barnea, G.; Schlessinger, J. ); Li, F. ); Nowell, P.C.; Glick, J. ); Weston, A.; Harris, C.C. ); Drabkin, H. ); Patterson, D. )

    1991-06-01

    PTPG, the gene for protein-tyrosine phosphatase {gamma} (PTP{gamma}), maps to a region of human chromosome 3, 3p21, that is frequently deleted in renal cell carcinoma and lung carcinoma. One of the functions of protein-tyrosine phosphatases is to reverse the effect of protein-tyrosine kinases, many of which are oncogenes, suggesting that some protein-tyrosine phosphatase genes may act as tumor suppressor genes. A hallmark of tumor suppressor genes is that they are deleted in tumors in which their inactivation contributes to the malignant phenotype. In this study, one PTP {gamma} allele was lost in 3 of 5 renal carcinoma cell lines and 5 of 10 lung carcinoma tumor samples tested. Importantly, one PTP {gamma} allele was lost in three lung tumors that had not lost flanking loci. PTP {gamma} mRNA was expressed in kidney cell lines and lung cell lines but not expressed in several hematopoietic cell lines tested. Thus, the PTP {gamma} gene has characteristics that suggest it as a candidate tumor suppressor gene at 3p21.

  19. CTCF Recruits Centromeric Protein CENP-E to the Pericentromeric/Centromeric Regions of Chromosomes through Unusual CTCF Binding Sites

    PubMed Central

    Xiao, Tiaojiang; Wongtrakoongate, Patompon; Trainor, Cecelia

    2015-01-01

    SUMMARY The role of CTCF in stabilizing long range interactions between chromatin sites essential for maintaining nuclear architecture is well established. Most of these interactions involve recruitment of the cohesin complex to chromatin via CTCF. We find that CTCF also interacts with the centromeric protein CENP-E both in vitro and in vivo. We identified CTCF sites in pericentric/centromeric DNA and found that early in mitosis CTCF binds and recruits CENP-E to these sites. Unlike most known CTCF genomic sites, the CTCF binding sites in the pericentric/centromeric regions interact strongly with the C-terminal fingers of CTCF. Over-expression of a small CENP-E fragment, targeted to these CTCF sites, results in delay in alignment of some chromosomes during mitosis, suggesting that the recruitment of CENP-E by CTCF is physiologically important. We conclude that CTCF helps recruit CENP-E to the centromere during mitosis, and may do so through a structure stabilized by the CTCF/CENP-E complex. PMID:26321640

  20. Construction and characterization of region-specific microdissection libraries and single-copy microclones for short arm of human chromosome 2

    SciTech Connect

    Tu, J.; Kao, F.T. |; Tong, S.; Qi, J.

    1994-07-01

    The short arm of human chromosome 2, comprising approximately 93 million bp, has been divided into four regions to construct region-specific microdissection libraries to facilitate physical mapping and gene cloning. These four regions include 2p23-p25 (designated 2P1), 2p21-p23 (2P2), 2p14-p16 (2P3), and 2p11-p13 (2P4). Together with three previously constructed microdissection libraries of 2P1, 2P2 and 2P4, a fourth library for the region 2P3 has been constructed and characterized to complete all four region-specific libraries for the entire 2p. The 2P3 library is very large, potentially comprising 1,000,000 recombinant microclones with insert sizes ranging between 50 and 800 bp and a mean of 250 bp. Approximately 40% of the microclones contain unique sequences. Of the 77 single-copy microclones analyzed, 66 clones (86%) hybridized to both human and chromosome 2 DNAs, indicating that they were derived from human and are chromosome 2 specific. The hybridizing HindIII genomic fragments for the 66 microclones have also been determined.

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

    SciTech Connect

    Aplin, H.M.; Hirst, K.L.; Crosby, A.H.; Dixon, M.J.

    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.

  2. The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region

    SciTech Connect

    Patterson, D.; Jones, C.; Hart, I.; Bleskan, J.; Berger, R.; Geyer, D. ); Eisenberg, S.P. ); Smith, M.F. Jr.; Arend, W.P. )

    1993-01-01

    The gene for human interleukin-1 receptor antagonist (IL1RN) has been assigned to chromosome 2 on the basis of Southern blot analysis of a series of human-Chinese hamster cell hybrids. Using a yeast artificial chromosome containing the IL1RN gene as a probe, the human IL1RN gene was localized to the long arm of chromosome 2 at band 2q14.2 by fluorescence in situ hybridization. This site is near the positions of genes for human IL-l[alpha], IL-1[beta], and types I and II IL-1 receptors, as reported by other laboratories. 23 refs., 1 fig., 1 tab.

  3. The Paternal Landscape along the Bight of Benin – Testing Regional Representativeness of West-African Population Samples Using Y-Chromosomal Markers

    PubMed Central

    Larmuseau, Maarten H. D.; Vessi, Andrea; Jobling, Mark A.; Van Geystelen, Anneleen; Primativo, Giuseppina; Biondi, Gianfranco; Martínez-Labarga, Cristina; Ottoni, Claudio; Decorte, Ronny; Rickards, Olga

    2015-01-01

    Patterns of genetic variation in human populations across the African continent are still not well studied in comparison with Eurasia and America, despite the high genetic and cultural diversity among African populations. In population and forensic genetic studies a single sample is often used to represent a complete African region. In such a scenario, inappropriate sampling strategies and/or the use of local, isolated populations may bias interpretations and pose questions of representativeness at a macrogeographic-scale. The non-recombining region of the Y-chromosome (NRY) has great potential to reveal the regional representation of a sample due to its powerful phylogeographic information content. An area poorly characterized for Y-chromosomal data is the West-African region along the Bight of Benin, despite its important history in the trans-Atlantic slave trade and its large number of ethnic groups, languages and lifestyles. In this study, Y-chromosomal haplotypes from four Beninese populations were determined and a global meta-analysis with available Y-SNP and Y-STR data from populations along the Bight of Benin and surrounding areas was performed. A thorough methodology was developed allowing comparison of population samples using Y-chromosomal lineage data based on different Y-SNP panels and phylogenies. Geographic proximity turned out to be the best predictor of genetic affinity between populations along the Bight of Benin. Nevertheless, based on Y-chromosomal data from the literature two population samples differed strongly from others from the same or neighbouring areas and are not regionally representative within large-scale studies. Furthermore, the analysis of the HapMap sample YRI of a Yoruban population from South-western Nigeria based on Y-SNPs and Y-STR data showed for the first time its regional representativeness, a result which is important for standard population and forensic genetic applications using the YRI sample. Therefore, the uniquely

  4. The Paternal Landscape along the Bight of Benin - Testing Regional Representativeness of West-African Population Samples Using Y-Chromosomal Markers.

    PubMed

    Larmuseau, Maarten H D; Vessi, Andrea; Jobling, Mark A; Van Geystelen, Anneleen; Primativo, Giuseppina; Biondi, Gianfranco; Martínez-Labarga, Cristina; Ottoni, Claudio; Decorte, Ronny; Rickards, Olga

    2015-01-01

    Patterns of genetic variation in human populations across the African continent are still not well studied in comparison with Eurasia and America, despite the high genetic and cultural diversity among African populations. In population and forensic genetic studies a single sample is often used to represent a complete African region. In such a scenario, inappropriate sampling strategies and/or the use of local, isolated populations may bias interpretations and pose questions of representativeness at a macrogeographic-scale. The non-recombining region of the Y-chromosome (NRY) has great potential to reveal the regional representation of a sample due to its powerful phylogeographic information content. An area poorly characterized for Y-chromosomal data is the West-African region along the Bight of Benin, despite its important history in the trans-Atlantic slave trade and its large number of ethnic groups, languages and lifestyles. In this study, Y-chromosomal haplotypes from four Beninese populations were determined and a global meta-analysis with available Y-SNP and Y-STR data from populations along the Bight of Benin and surrounding areas was performed. A thorough methodology was developed allowing comparison of population samples using Y-chromosomal lineage data based on different Y-SNP panels and phylogenies. Geographic proximity turned out to be the best predictor of genetic affinity between populations along the Bight of Benin. Nevertheless, based on Y-chromosomal data from the literature two population samples differed strongly from others from the same or neighbouring areas and are not regionally representative within large-scale studies. Furthermore, the analysis of the HapMap sample YRI of a Yoruban population from South-western Nigeria based on Y-SNPs and Y-STR data showed for the first time its regional representativeness, a result which is important for standard population and forensic genetic applications using the YRI sample. Therefore, the uniquely

  5. Pure chromosome-specific PCR libraries from single sorted chromosomes.

    PubMed Central

    VanDevanter, D R; Choongkittaworn, N M; Dyer, K A; Aten, J; Otto, P; Behler, C; Bryant, E M; Rabinovitch, P S

    1994-01-01

    Chromosome-specific DNA libraries can be very useful in molecular and cytogenetic genome mapping studies. We have developed a rapid and simple method for the generation of chromosome-specific DNA sequences that relies on polymerase chain reaction (PCR) amplification of a single flow-sorted chromosome or chromosome fragment. Previously reported methods for the development of chromosome libraries require larger numbers of chromosomes, with preparation of pure chromosomes sorted by flow cytometry, generation of somatic cell hybrids containing targeted chromosomes, or a combination of both procedures. These procedures are labor intensive, especially when hybrid cell lines are not already available, and this has limited the generation of chromosome-specific DNA libraries from nonhuman species. In contrast, a single sorted chromosome is a pure source of DNA for library production even when flow cytometric resolution of chromosome populations is poor. Furthermore, any sorting cytometer may be used with this technique. Using this approach, we demonstrate the generation of PCR libraries suitable for both molecular and fluorescence in situ hybridization studies from individual baboon and canine chromosomes, separate human homologues, and a rearranged marker chromosome from a transformed cell line. PCR libraries specific to subchromosomal regions have also been produced by sorting a small chromosome fragment. This simple and rapid technique will allow generation of nonhuman linkage maps and probes for fluorescence in situ hybridization and the characterization of marker chromosomes from solid tumors. In addition, allele-specific libraries generated by this strategy may also be useful for mapping genetic diseases. Images PMID:8016078

  6. Exclusion of Linkage to the CDL1 Gene Region on Chromosome 3q26.3 in Some Familial Cases of Cornelia de Lange Syndrome

    PubMed Central

    Krantz, Ian D.; Tonkin, Emma; Smith, Melanie; Devoto, Marcella; Bottani, Armand; Simpson, Claire; Hofreiter, Mary; Abraham, Vinod; Jukofsky, Lori; Conti, Brian P.; Strachan, Tom; Jackson, Laird

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a complex developmental disorder consisting of characteristic facial features, limb abnormalities, hirsutism, ophthalmologic involvement, gastroesophageal dysfunction, hearing loss, as well as growth and neuro-developmental retardation. Most cases of CdLS appear to be sporadic. Familial cases are rare and indicate autosomal dominant inheritance. Several individuals with CdLS have been reported with chromosomal abnormalities, suggesting candidate genomic regions within which the causative gene(s) may lie. A CdLS gene location (CDL1) has been assigned to 3q26.3 based on phenotypic overlap with the duplication 3q syndrome (critical region 3q26.2-q27) and the report of a CdLS individual with a balanced de novo t(3;17)(q26.3;q23.1). It has been postulated that a gene within the dup3q critical region results in the CdLS when deleted or mutated. We have performed a linkage analysis to the minimal critical region for the dup3q syndrome (that encompasses the translocation breakpoint) on chromosome 3q in 10 rare familial cases of CdLS. Nineteen markers spanning a region of approximately 40 Mb (37 cM) were used. Results of a multipoint linkage analysis demonstrated total lod-scores that were negative across the chromosome 3q26-q27 region. In 4/10 families, lod-scores were less than −2 in the 2 cM region encompassing the translocation, while in the remaining 6/10 families, lod-scores could not exclude linkage to this region. These studies indicate that in some multicase families, the disease gene does not map to the CDL1 region at 3q26.3. PMID:11391654

  7. Detailed deletion mapping in sporadic breast cancer at chromosomal region 17p13 distal to the TP53 gene: association with clinicopathological parameters.

    PubMed

    Seitz, S; Poppe, K; Fischer, J; Nothnagel, A; Estévez-Schwarz, L; Haensch, W; Schlag, P M; Scherneck, S

    2001-07-01

    Chromosome 17p is among the most frequently deleted regions in a variety of human malignancies including breast cancer. This study has further refined the localization of a putative tumour suppressor gene (TSG) at 17p13 distal to the TP53 gene in breast carcinomas. It was found that 73% (37 of 51) of the breast tumours exhibited loss of heterozygosity (LOH) at one or more loci at 17p13. The allelic loss patterns of these tumours suggest the presence of at least seven commonly deleted regions on 17p13. The three most frequently deleted regions were mapped at chromosomal location 17p13.3-17p13.2 between the markers D17S831 and D17S1845 (56% LOH), at 17p13.1 between D17S1810 and D17S1832 (53% LOH), and at 17p13.1 between D17S938 and TP53 (55% LOH). A significant correlation was found between loss at 17p13 and tumour grade, size, proliferative activity, and oestrogen receptor (ER) status. Losses at 17p13 were seen more frequently in large and poorly differentiated tumours with high proliferative activity. These data support and extend previous reports on the presence of a putative TSG(s) at chromosomal region 17p13 distal to the TP53 gene and show that different subsets of LOH are associated with more aggressive tumour behaviour. PMID:11439364

  8. Isolation of region-specific cosmids by hybridization with microdissection clones from human chromosome 10q11. 1-q21. 1

    SciTech Connect

    Karakawa, Katsu; Takami, Koji; Fujita, Shoichi Osaka Univ. Medical School, Fukushima-ku, Osaka ); Nakamura, Tsutomu; Takai, Shin-ichiro; Nishisho, Isamu ); Jones, C. ); Ohta, Tohru; Jinno, Yoshihiro; Niikawa, Norio )

    1993-08-01

    A region-specific plasmid library composed of 20,000 recombinants was constructed by microdissection of human chromosome 10 (10q11.2-q21.1) and subsequent amplification with the primer-linker method of polymerase chain reaction (PCR). Hybridization with total human DNA showed that 32 of 217 microclones studied contained highly repetitive sequences. Further analysis of the remaining 185 microclones proved that 43 microclones, each having an insert longer than 200 bp, contained unique sequences of human chromosome 10 origin. Twenty-five microclones randomly selected from the 43 were used directly as probes to isolate corresponding cosmid clones, resulting in 32 cosmids corresponding to 14 microclones. Of the 25 cosmids that could be mapped by fluorescence in situ hybridization, 24 proved to originate from the microdissected or adjacent region (10p11.2-q22.3)and 1 from a rather distal region (10q24.3-q25.1). In addition, 15 of the 32 cosmids revealed restriction fragment length polymorphisms, including 1 with a variable number of tandem repeats marker. The microdissection library and the obtained cosmids are valuable resources for constructing high-resolution physical and linkage maps of the pericentromeric region of chromosome 10, where the gene predisposing to multiple endocrine neoplasia type 2A (MEN2A) has been mapped. 30 refs., 3 figs., 3 tabs.

  9. Detailed ordering of markers localizing to the Xq26-Xqter region of the human X chromosome by the use of an interspecific Mus spretus mouse cross

    SciTech Connect

    Avner, P.; Amar, L.; Arnaud, D.; Hanauer, A.; Cambrou, J.

    1987-03-01

    Five probes localizing to the Xq26-Xqter region of the human X chromosome have been genetically mapped on the mouse X chromosome using an interspecific cross involving Mus spretus to a contiguous region lying proximally to the Tabby (Ta) locus. Pedigree and recombinational analysis establish the marker order as being Hprt-FIX-c11-G6PD-St14-1. The size of this contiguous region is such that the X-linked muscular dystrophy (mdx) mouse mutation probably maps within this segment. This in turn suggests that it is highly improbable that the mouse mdx locus represents a model for Duchenne muscular dystrophy (DMD). It is, however, compatible with the idea that this mutation may correspond in man to Emery Dreifuss muscular dystrophy. The high frequency of restriction fragment length polymorphisms found in this interspecific system for all the human cross-reacting probes examined up until now, using only a limited number of restriction enzymes, suggests that the Mus spretus mapping system may be of great potential value for establishing the linkage relationships existing in man when conserved chromosomal regions are concerned and human/mouse cross-reacting probes are available or can be obtained.

  10. Autosomal dominant familial spastic paraplegia: reduction of the FSP1 candidate region on chromosome 14q to 7 cM and locus heterogeneity.

    PubMed Central

    Gispert, S; Santos, N; Damen, R; Voit, T; Schulz, J; Klockgether, T; Orozco, G; Kreuz, F; Weissenbach, J; Auburger, G

    1995-01-01

    Three large pedigrees of German descent with autosomal dominant "pure" 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 pedigrees D and S, the gene locus could be excluded from the whole FSP1 region, confirming the locus heterogeneity of autosomal dominant FSP. PMID:7825576

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

    PubMed Central

    Šedová, Lucie; Pravenec, Michal; Křenová, Drahomíra; Kazdová, Ludmila; Zídek, Václav; Krupková, Michaela; Liška, František; Křen, Vladimír; Šeda, Ondřej

    2016-01-01

    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 syndrome

  12. Haplotype frequencies of 17 Y-chromosomal short tandem repeat loci from the Cukurova region of Turkey

    PubMed Central

    Serin, Ayse; Canan, Husniye; Alper, Behnan; Sertdemir, Yasar

    2011-01-01

    Aim To investigate the distribution of 17 Y-short tandem repeat (STR) loci in the population of the Cukurova region of Turkey. Methods In the period between 2009 and 2010, we investigated the distribution of 17 Y-STRs in a sample of 249 unrelated healthy men from the Cukurova region of Turkey. Genomic DNA was extracted with InstaGene matrix and Y-STRs were determined using the AmpFISTR Yfiler PCR amplification kit. Gene and haplotype diversity values were estimated using the Arlequin software. To compare our data to other populations, population pairwise genetic distances and associated probability values were calculated using the Y Chromosome Haplotype Reference Database Web site software. Results At 17 Y-STR loci we detected 148 alleles. The lowest gene diversity in this region was 0.51 for DYS391 and the highest 0.95 for DYS385a/b. Haplotype diversity was 0.9997 ± 0.0004. We compared our data with haplotype data of other Turkish populations and no significant differences were found, except with Ankara population (Φst = 0.025, P = 0.018). Comparisons were also made with the neighboring populations using analysis of molecular variance of the Y-STR loci genetic structure and our population was nearest to Lenkoran-Azerbaijani (Φst = 0.012, P = 0.068) and Iranian Ahvaz population (Φst = 0.007, P = 0.173), followed by Greek (Φst = 0.026, P = 0.000) and Russian (Φst = 0.048, P = 0.000) population. Other countries like Portugal, Spain, Italy, Egypt, Israel (Palestinian Authority Area), and Taiwan showed a high genetic distance from our population. Conclusion Our study showed that Y-STR polymorphisms were a powerful discrimination tool for routine forensic applications and could be used in genealogical investigations. PMID:22180269

  13. Physical mapping of the chromosome 7 breakpoint region in an SLOS patient with t(7;20)X(q32.1;q13.2)

    SciTech Connect

    Alley, T.L.; Wallace, M.R.; Scherer, S.W.

    1997-01-31

    Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder characterized by multiple congenital anomalies and mental retardation. SLOS has an associated defect in cholesterol biosynthesis, but the molecular genetic basis of this condition has not yet been elucidated. Previously our group reported a patient with a de novo balanced translocation [t(7;20)(q32.1;q13.2)] fitting the clinical and biochemical profile of SLOS. Employing fluorescence in situ hybridization (FISH), a 1.8 Mb chromosome 7-specific yeast artificial chromosome (YAC) was identified which spanned the translocation breakpoint in the reported patient. The following is an update of the on-going pursuit to physically and genetically map the region further, as well as the establishment of candidate genes in the 7q32.1 breakpoint region. 11 refs., 1 fig.

  14. Chromosome region maintenance 1 expression and its association with clinical pathological features in primary carcinoma of the liver

    PubMed Central

    XIE, QIAO-LING; LIU, YUE; ZHU, YING

    2016-01-01

    Liver cancer is the third leading cause of cancer-associated mortality worldwide. Recurrence and metastasis are the major factors affecting the prognosis; thus, investigation of the underlying molecular mechanisms of invasion and metastasis, and detection of novel drug target may improve the mortality rate of liver cancer patients. Chromosome region maintenance 1 (CRM1) recognizes specific leucine-rich nuclear export signal sequences, and its overexpression is associated with tumor-suppressor gene inactivation, proliferation, invasion and resistance to chemotherapy. The aim of the present study was to examine the association of CRM1 expression with the clinical and pathological features of primary liver cancer. In total, 152 cases diagnosed with liver cancer were included. CRM1 expression was detected in cancer tissues and adjacent normal tissues by immunohistochemical assay. No statistically significant difference was found between the CRM1 expression levels in tumor and adjacent normal tissues (P=0.106). However, CRM1 expression in adjacent normal tissues was higher compared with that in tumor tissues in the negative hepatitis B envelope antigen (HBeAg; P=0.029) and low differentiation (P=0.004) groups. In tumor tissues, CRM1 expression was significantly correlated with differentiation (P=0.045), whereas in adjacent normal tissues, CRM1 expression was significantly correlated with the tumor diameter (P=0.004). Therefore, it can be concluded that CRM1 is highly expressed in both tumor and adjacent normal tissues. Furthermore, CRM1 expression is associated with the tumor differentiation degree and diameter. Lower differentiation and larger tumor diameter resulted in higher CRM1 expression in adjacent normal tissues, and higher tendency for invasion and metastasis. In addition, the risk of invasion and metastasis remains in chronic hepatitis B patients with negative HBeAg. PMID:27347018

  15. Role of the pseudoautosomal region in sex-chromosome pairing during male meiosis: Meiotic studies in a man with a deletion of distal Xp

    SciTech Connect

    Mohandas, T.K.; Passage, M.B.; Yen, P.H.; Speed, R.M.; Chandley, A.C.; Shapiro, L.J. )

    1992-09-01

    Meiotic studies were undertaken in a 24-year-old male patient with short stature, chondrodysplasia punctata, ichthyosis, steroid sulfatase deficiency, and mild mental retardation with an inherited cytologically visible deletion of distal Xp. Molecular investigations showed that the pseudoautosomal region as well as the steroid sulfatase gene were deleted, but telomeric sequences were present at the pter on the deleted X chromosome. A complete failure of sex-chromosome pairing was observed in the primary spermatocytes of the patient. Telomeric approaches between the sex chromosomes were made at zygotene in some cells, but XY synaptonemal complex was formed. The sex chromosomes were present as univalents at metaphase I, and germ-cell development was arrested between metaphase I and metaphase II in the vast majority of cells, consistent with the azoospermia observed in the patient. The failure of XY pairing in this individual indicates that the pseudoautosomal sequences play an important role in initiating XY pairing and formation of synaptonemal complex at meiosis. 36 refs., 6 figs.

  16. Multicolor FISH mapping with Alu-PCR-amplified YAC clone DNA determines the order of markers in the BRCA1 region on chromosome 17q12-q21

    SciTech Connect

    Flejter, W.J.; Glover, T.W.; Barcroft, C.L.; Guo, Sun Wei; Boehnke, M.; Chandrasekharappa, S.; Collins, F.S. Howard Hughes Medical Institute, Ann Arbor, MI ); Lynch, E.D. ); Hayes, S. ); Weber, B.L. )

    1993-09-01

    A gene designated BRCA1, implicated in the susceptibility to early-onset familial breast cancer, has recently been localized to chromosome 17q12-q21. To date, the order of DNA markers mapped within this region has been based on genetic linkage analysis. The authors report the use of multicolor fluorescence in situ hybridization to establish a physically based map of five polymorphic DNA markers and 10 cloned genes spanning this region. Three cosmid clones and Alu-PCR-Generated products derived from 12 yeast artificial chromosome clones representing each of these markers were used in two-color mapping experiments to determine an initial proximity of markers relative to each other on metaphase chromosomes. Interphase mapping was then employed to determine the order and orientation of closely spaced loci by direct visualization of fluorescent signals following hybridization of three probes, each detected in a different color. Statistical analysis of the combined data suggests that the order of markers in the BRCA1 regions is cen-THRA1-TOP2-GAS-OF2-17HSD-248yg9-RNU2-OF3-PPY/p131-EPB3-Mfd188-WNT3-HOX2-GP3A-tel. This map is consistent with that determined by radiation-reduced hybrid mapping and will facilitate positional cloning strategies in efforts to isolate and characterize the BRCA1 gene. 27 refs., 2 figs., 3 tabs.

  17. Strain of Synechocystis PCC 6803 with Aberrant Assembly of Photosystem II Contains Tandem Duplication of a Large Chromosomal Region

    PubMed Central

    Tichý, Martin; Bečková, Martina; Kopečná, Jana; Noda, Judith; Sobotka, Roman; Komenda, Josef

    2016-01-01

    Cyanobacterium Synechocystis PCC 6803 represents a favored model organism for photosynthetic studies. Its easy transformability allowed construction of a vast number of Synechocystis mutants including many photosynthetically incompetent ones. However, it became clear that there is already a spectrum of Synechocystis “wild-type” substrains with apparently different phenotypes. Here, we analyzed organization of photosynthetic membrane complexes in a standard motile Pasteur collection strain termed PCC and two non-motile glucose-tolerant substrains (named here GT-P and GT-W) previously used as genetic backgrounds for construction of many photosynthetic site directed mutants. Although, both the GT-P and GT-W strains were derived from the same strain constructed and described by Williams in 1988, only GT-P was similar in pigmentation and in the compositions of Photosystem II (PSII) and Photosystem I (PSI) complexes to PCC. In contrast, GT-W contained much more carotenoids but significantly less chlorophyll (Chl), which was reflected by lower level of dimeric PSII and especially trimeric PSI. We found that GT-W was deficient in Chl biosynthesis and contained unusually high level of unassembled D1-D2 reaction center, CP47 and especially CP43. Another specific feature of GT-W was a several fold increase in the level of the Ycf39-Hlip complex previously postulated to participate in the recycling of Chl molecules. Genome re-sequencing revealed that the phenotype of GT-W is related to the tandem duplication of a large region of the chromosome that contains 100 genes including ones encoding D1, Psb28, and other PSII-related proteins as well as Mg-protoporphyrin methylester cyclase (Cycl). Interestingly, the duplication was completely eliminated after keeping GT-W cells on agar plates under photoautotrophic conditions for several months. The GT-W strain without a duplication showed no obvious defects in PSII assembly and resembled the GT-P substrain. Although, we do not

  18. Strain of Synechocystis PCC 6803 with Aberrant Assembly of Photosystem II Contains Tandem Duplication of a Large Chromosomal Region.

    PubMed

    Tichý, Martin; Bečková, Martina; Kopečná, Jana; Noda, Judith; Sobotka, Roman; Komenda, Josef

    2016-01-01

    Cyanobacterium Synechocystis PCC 6803 represents a favored model organism for photosynthetic studies. Its easy transformability allowed construction of a vast number of Synechocystis mutants including many photosynthetically incompetent ones. However, it became clear that there is already a spectrum of Synechocystis "wild-type" substrains with apparently different phenotypes. Here, we analyzed organization of photosynthetic membrane complexes in a standard motile Pasteur collection strain termed PCC and two non-motile glucose-tolerant substrains (named here GT-P and GT-W) previously used as genetic backgrounds for construction of many photosynthetic site directed mutants. Although, both the GT-P and GT-W strains were derived from the same strain constructed and described by Williams in 1988, only GT-P was similar in pigmentation and in the compositions of Photosystem II (PSII) and Photosystem I (PSI) complexes to PCC. In contrast, GT-W contained much more carotenoids but significantly less chlorophyll (Chl), which was reflected by lower level of dimeric PSII and especially trimeric PSI. We found that GT-W was deficient in Chl biosynthesis and contained unusually high level of unassembled D1-D2 reaction center, CP47 and especially CP43. Another specific feature of GT-W was a several fold increase in the level of the Ycf39-Hlip complex previously postulated to participate in the recycling of Chl molecules. Genome re-sequencing revealed that the phenotype of GT-W is related to the tandem duplication of a large region of the chromosome that contains 100 genes including ones encoding D1, Psb28, and other PSII-related proteins as well as Mg-protoporphyrin methylester cyclase (Cycl). Interestingly, the duplication was completely eliminated after keeping GT-W cells on agar plates under photoautotrophic conditions for several months. The GT-W strain without a duplication showed no obvious defects in PSII assembly and resembled the GT-P substrain. Although, we do not exactly

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

    PubMed

    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

  20. Mouse models of Down syndrome: how useful can they be? Comparison of the gene content of human chromosome 21 with orthologous mouse genomic regions.

    PubMed

    Gardiner, Katheleen; Fortna, Andrew; Bechtel, Lawrence; Davisson, Muriel T

    2003-10-30

    With an incidence of approximately 1 in 700 live births, Down syndrome (DS) remains the most common genetic cause of mental retardation. The phenotype is assumed to be due to overexpression of some number of the >300 genes encoded by human chromosome 21. Mouse models, in particular the chromosome 16 segmental trisomies, Ts65Dn and Ts1Cje, are indispensable for DS-related studies of gene-phenotype correlations. Here we compare the updated gene content of the finished sequence of human chromosome 21 (364 genes and putative genes) with the gene content of the homologous mouse genomic regions (291 genes and putative genes) obtained from annotation of the public sector C57Bl/6 draft sequence. Annotated genes fall into one of three classes. First, there are 170 highly conserved, human/mouse orthologues. Second, there are 83 minimally conserved, possible orthologues. Included among the conserved and minimally conserved genes are 31 antisense transcripts. Third, there are species-specific genes: 111 spliced human transcripts show no orthologues in the syntenic mouse regions although 13 have homologous sequences elsewhere in the mouse genomic sequence, and 38 spliced mouse transcripts show no identifiable human orthologues. While these species-specific genes are largely based solely on spliced EST data, a majority can be verified in RNA expression experiments. In addition, preliminary data suggest that many human-specific transcripts may represent a novel class of primate-specific genes. Lastly, updated functional annotation of orthologous genes indicates genes encoding components of several cellular pathways are dispersed throughout the orthologous mouse chromosomal regions and are not completely represented in the Down syndrome segmental mouse models. Together, these data point out the potential for existing mouse models to produce extraneous phenotypes and to fail to produce DS-relevant phenotypes. PMID:14585506

  1. Mapping immunoglobulin gene-related DNA probes to the central region of normal and pericentrically inverted human chromosome 2

    SciTech Connect

    Lautner-Rieske, A.; Zachau, H.G.; Hameister, H.; Barbi, G.

    1993-05-01

    Several immunoglobulin {kappa}-related sequences were transposed in evolution from the short arm to the long arm of chromosome 2. The common pericentric inversion of this chromosome found in present-day populations results in an apparent reinversion of those sequences to the short arm and the transposition of the {kappa} and CD8{alpha} loci to the long arm. This is shown by in situ hybridization and PFGE experiments with hybridization probes from both arms of chromosome 2, i.e., from 2cen-p12 and 2cen-q13. The inversion breakpoints lie outside of all hybridization sites, and the inversion is described as inv(2)(p12q14). The possibility of common breakpoints in ancient and present-day pericentric inversions is discussed. 30 refs., 5 figs., 1 tab.

  2. Irradiation hybrids for human chromosome 11: Characterization and use for generating region-specific markers in 11q14-q23

    SciTech Connect

    Gillett, G.T.; Hunt, D.M.; West, L.F.; Fox, M.F.; Povey, S.; Benham, F.J. ); McConville, C.M.; Byrd, P.J.; Stankovic, T.; Taylor, A.M. )

    1993-02-01

    High-dose irradiation hybrids containing fragments of chromosome 11 have been generated, with a view to isolating new region-specific markers. Forty-seven lines were scored for 34 markers: average retention was 6%. Fourteen lines contain markers from 11q14 to 11q23. One of these, Jo12, has 11q markers extending from tyrosinase (q14-q21) to PBGD (q23.3) plus one marker (TYRL, p11.2) from 11p. In situ hybridization using Alu PCR products form Jo12 as probe confirmed that the human DNA is derived from two regions, one in proximal 11p and a second, larger region in 11q23. Plasmid libraries of Alu PCR products from this and three other hybrids have been made. Six of eight recombinants identified as having single-copy inserts were mapped back to the regions of 11q22-q23 detected in the originating hybrid; only one mapped to a region not originally detected, and one was of hamster origin. These six clones provide new markers in 11q22-q23 that can be used directly for polymorphism studies. This series of hybrids is therefore a valuable resource for the rapid generation of markers from specific, defined regions of chromosomes 11. 50 refs., 2 figs., 4 tabs.

  3. Detection of chromosomal blaCTX-M-15 in Escherichia coli O25b-B2-ST131 isolates from the Kinki region of Japan.

    PubMed

    Hirai, Itaru; Fukui, Naoki; Taguchi, Masumi; Yamauchi, Kou; Nakamura, Tatsuya; Okano, Sho; Yamamoto, Yoshimasa

    2013-12-01

    Escherichia coli O25b-B2-ST131 isolates harbouring bla(CTX-M-15) are distributed worldwide. The bla(CTX-M-15) transposition unit has often been found on plasmids and the genetic contexts have been examined; however, less is known about the frequency and contexts of the bla(CTX-M-15) transposition unit on the chromosome. This study was performed to determine the chromosomal location of the bla(CTX-M-15) transposition unit and to analyse the molecular structure of the region surrounding the bla(CTX-M-15) transposition unit in E. coli O25b-B2-ST131 isolates. Twenty-two E. coli O25b-B2-ST131 strains harbouring bla(CTX-M-15) that had been isolated from university hospital patients and nursing home residents in the Kinki region of Japan were examined. Inverse PCR (iPCR) targeting bla(CTX-M-15) was performed to classify the molecular structure of the region surrounding the bla(CTX-M-15) transposition unit. The isolates were classified into nine types (types A-I) considering the iPCR results; type A was the most prevalent type (13/22 isolates). Sequences of the iPCR-amplified DNA fragments showed that the bla(CTX-M-15) transposition unit consisted of ISEcp1, bla(CTX-M-15) and orf477Δ. A homology search of the obtained sequences showed that the bla(CTX-M-15) transposition unit was inserted into different chromosomal regions in eight of the nine classified types. Although 21 of the 22 E. coli isolates possessed chromosomally located bla(CTX-M-15) transposition units, clonal spread was not evident on pulsed-field gel electrophoresis (PFGE) analysis. Taken together, these data indicate that certain E. coli O25b-B2-ST131 strains harbouring chromosomal bla(CTX-M-15) have emerged and spread in the Kinki region of Japan. PMID:24091130

  4. Regional localisation of 19 brain expressed sequence tags to human chromosome 11 using PCR amplification of somatic cell hybrid DNAs.

    PubMed

    Slorach, E M; Polymeropoulos, M H; Evans, K L; Seawright, A; Fletcher, J M; Porteous, D J; Brookes, A J

    1995-01-01

    Expressed sequence tags (ESTs) provide an efficient route to the identification of genes involved in normal development and in disease. PCR amplification of somatic cell hybrid DNAs was used to localise 22 brain-derived ESTs to subregions of human chromosome 11. Problems encountered with the standardised PCR conditions were overcome by optimising the annealing temperatures and the use of "touchdown" PCR. Amplification of the correct target sequence allowed the mapping of 19 ESTs, 8 to the short arm and 11 to the long arm of chromosome 11. No definitive localisation could be determined for the three remaining ESTs. PMID:7736794

  5. Mapping strategies: Chromosome 16 workshop. Final technical report

    SciTech Connect

    Not Available

    1989-12-31

    The following topics from a workshop on chromosome 16 are briefly discussed: genetic map of chromosome 16; chromosome breakpoint map of chromosome 16; integrated physical/genetic map of chromosome 16; pulsed field map of the 16p13.2--p13.3 region (3 sheets); and a report of the HGM10 chromosome 16 committee.

  6. Chromosomes, conflict, and epigenetics: chromosomal speciation revisited.

    PubMed

    Brown, Judith D; O'Neill, Rachel J

    2010-01-01

    Since Darwin first noted that the process of speciation was indeed the "mystery of mysteries," scientists have tried to develop testable models for the development of reproductive incompatibilities-the first step in the formation of a new species. Early theorists proposed that chromosome rearrangements were implicated in the process of reproductive isolation; however, the chromosomal speciation model has recently been questioned. In addition, recent data from hybrid model systems indicates that simple epistatic interactions, the Dobzhansky-Muller incompatibilities, are more complex. In fact, incompatibilities are quite broad, including interactions among heterochromatin, small RNAs, and distinct, epigenetically defined genomic regions such as the centromere. In this review, we will examine both classical and current models of chromosomal speciation and describe the "evolving" theory of genetic conflict, epigenetics, and chromosomal speciation. PMID:20438362

  7. A high-resolution annotated physical map of the human chromosome 13q12-13 region containing the breast cancer susceptibility locus BRCA2.

    PubMed Central

    Fischer, S G; Cayanis, E; de Fatima Bonaldo, M; Bowcock, A M; Deaven, L L; Edelman, I S; Gallardo, T; Kalachikov, S; Lawton, L; Longmire, J L; Lovett, M; Osborne-Lawrence, S; Rothstein, R; Russo, J J; Soares, M B; Sunjevaric, I; Venkatraj, V S; Warburton, D; Zhang, P; Efstratiadis, A

    1996-01-01

    Various types of physical mapping data were assembled by developing a set of computer programs (Integrated Mapping Package) to derive a detailed, annotated map of a 4-Mb region of human chromosome 13 that includes the BRCA2 locus. The final assembly consists of a yeast artificial chromosome (YAC) contig with 42 members spanning the 13q12-13 region and aligned contigs of 399 cosmids established by cross-hybridization between the cosmids, which were selected from a chromosome 13-specific cosmid library using inter-Alu PCR probes from the YACs. The end sequences of 60 cosmids spaced nearly evenly across the map were used to generate sequence-tagged sites (STSs), which were mapped to the YACs by PCR. A contig framework was generated by STS content mapping, and the map was assembled on this scaffold. Additional annotation was provided by 72 expressed sequences and 10 genetic markers that were positioned on the map by hybridization to cosmids. Images Fig. 3 PMID:8570617

  8. Diagnostic and prognostic significance of genetic regional heterogeneity in meningiomas1

    PubMed Central

    Pfisterer, Wolfgang K.; Hank, Nicole C.; Preul, Mark C.; Hendricks, William P.; Pueschel, Jeanette; Coons, Stephen W.; Scheck, Adrienne C.

    2004-01-01

    We analyzed the frequency and regional distribution of cells with genetic abnormalities of chromosomes 1, 14, and 22 in meningiomas. This data was evaluated for correlation to the clinical outcome of the patients. Eight defined areas of each of 77 paraffin-embedded meningioma samples (59 grade I, 13 grade II, and 5 grade III) were analyzed by fluorescent in situ hybridization using bacterial artificial chromosome probes localized to chromosomes 1p36.32, 1q25.3, 14q13.3, 14q32.12, 22q11.2, and 22q12.1-3. Chromosome deletion was considered to be regionally heterogeneous if <7 regions showed cells with chromosome deletions. Deletion of 1p occurred in 35% of the grade I tumors. Distribution of cells with 1p deletion was regionally heterogeneous in 25% and homogeneous in 10% of grade I tumors. Distribution of cells with deletion of 1p was regionally heterogeneous in 23% and homogeneous in 69% of the grade II tumors. All grade III meningiomas had homogeneous distribution of cells with deletion of chromosome 1p. Distribution of cells with deletion of 14q was regionally heterogeneous in 27% and homogeneous in 2% of the grade I meningiomas, heterogeneous in 31% and homogeneous in 62% of the grade II tumors, and heterogeneous in 40% and homogeneous in 60% of the grade III meningiomas. Distribution of cells with deletion of 22q was regionally heterogeneous in 15% and homogeneous in 3% of the grade I tumors, heterogeneous in 15% and homogeneous in 31% of grade II tumors, and homogeneous in 20% of the grade III meningiomas. Distribution of cells with trisomy 22q was regionally heterogeneous in 10% of grade I tumors, heterogeneous in 23% of grade II, and homogeneous in 80% of grade III meningiomas. The proportion of patients with a deletion of 22q (either homogeneous or heterogeneous) who had recurrence was greater than the proportion of those without 22q deletion who had recurrence, and deletion of 22q was significantly associated with radiologically detected recurrence (P < 0

  9. Characterization of a DNA sequence family in the Prader-Willi/Angelman syndrome chromosome region in 15q11-q13

    SciTech Connect

    Dittrich, B.; Knoblauch, H.; Buiting, K.; Horsthemke, B. )

    1993-04-01

    IR4-3R (D15S11) is an anonymous DNA sequence from human chromosome 15. Using YAC cloning and restriction enzyme analysis, the authors have found that IR4-3R detects five related DNA sequences, which are spread over 700 kb within the Prader-Willi/Angelman syndrome chromosome region in 15q11-q 13. The RsaI and StyI polymorphisms, which were described previously, are associated with the most proximal copy of IR4-3R and are in strong linkage disequilibrium. IR4-3R represents the third DNA sequence family that has been identified in 15q11-q13. 14 refs., 2 figs., 1 tab.

  10. Fluorescence in situ hybridization mapping of the mouse platelet endothelial cell adhesion molecule-1 (PECAM1) to mouse chromosome 6, region F3-G1

    SciTech Connect

    Xie, Yong; Muller, W.A.

    1996-10-15

    Human platelet/endothelial cell adhesion molecule-1 (PECAM1), an important member of the immunoglobulin gene superfamily, is widely distributed on cells of the vascular system and mediates cellular interactions through both homophilic and heterophilic adhesive mechanisms. The function of PECAM1 in vitro has begun to be understood, but its function in vivo is yet to be established. To study the function of PECAM1 in vivo, its mouse counterpart was identified and its cDNA gene isolated and characterized. In this study, the mouse chromosomal localization was determined for the mouse gene encoding Pecam. Fluorescence in situ hybridization was used to map the Pecam gene on mouse chromosome 6, region F3-G1. 12 refs., 2 figs.

  11. Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region.

    PubMed

    Chrast, R; Scott, H S; Chen, H; Kudoh, J; Rossier, C; Minoshima, S; Wang, Y; Shimizu, N; Antonarakis, S E

    1997-06-01

    As part of our effort to clone genes of human chromosome 21 that may contribute to Down syndrome, we have previously isolated four exons with homology to Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of fruit fly neurogenesis. These exons were used to clone and characterize two human homologs of the Drosophila sim gene, SIM1 and SIM2, which map to chromosomes 6q16.3-q21 and 21q22.2, respectively; SIM2 maps within the so-called Down syndrome chromosomal region. Recently, two mouse homologs, Sim1 and Sim2, also have been identified. There is a high level of homology among human, mouse, and Drosophila sim genes in their amino-terminal half where the conserved bHLH, PAS1, PAS2, and HST domains are present. In contrast, the carboxy-terminal parts are only homologous between SIM1 and Sim1 and SIM2 and Sim2. Two isoforms (SIM2 and SIM2s) of human SIM2 have been detected that differ in their 3' ends. Northern blot analysis revealed one mRNA SIM1 species of approximately 9.5 kb and four different mRNA SIM2 species of 2.7, 3, 4.4, and 6 kb in human fetal kidney. The function of both human SIM1 and SIM2 is unknown. However, three copies of SIM2 may contribute to some specific Down syndrome phenotypes because of (1) mapping position, (2) potential function as transcriptional repressor, (3) likely dimerization with other transcription factors, (4) the temporal and spatial expression pattern of mouse Sim2, and (5) the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis. PMID:9199934

  12. Medium-range restriction maps of five chromosomes of Leishmania infantum and localization of size-variable regions

    SciTech Connect

    Ravel, C.; Wincker, P.; Blaineau, C.

    1996-08-01

    This report describes the localization of the gene coding for human deoxyhypusine synthase (DHPS) to human chromosome 19p13.11-p13.12 using fluorescence in situ hybridization and somatic cell hybridization analysis. DHPS plays a vital role in the modification of hypusine. 10 refs., 1 fig.

  13. Regional Differences in the Accumulation of SNPs on the Male-Specific Portion of the Human Y Chromosome Replicate Autosomal Patterns: Implications for Genetic Dating.

    PubMed

    Trombetta, Beniamino; D'Atanasio, Eugenia; Massaia, Andrea; Myres, Natalie M; Scozzari, Rosaria; Cruciani, Fulvio; Novelletto, Andrea

    2015-01-01

    Factors affecting the rate and pattern of the mutational process are being identified for human autosomes, but the same relationships for the male specific portion of the Y chromosome (MSY) are not established. We considered 3,390 mutations occurring in 19 sequence bins identified by sequencing 1.5 Mb of the MSY from each of 104 present-day chromosomes. The occurrence of mutations was not proportional to the amount of sequenced bases in each bin, with a 2-fold variation. The regression of the number of mutations per unit sequence against a number of indicators of the genomic features of each bin, revealed the same fundamental patterns as in the autosomes. By considering the sequences of the same region from two precisely dated ancient specimens, we obtained a calibrated region-specific substitution rate of 0.716 × 10-9/site/year. Despite its lack of recombination and other peculiar features, the MSY then resembles the autosomes in displaying a marked regional heterogeneity of the mutation rate. An immediate implication is that a given figure for the substitution rate only makes sense if bound to a specific DNA region. By strictly applying this principle we obtained an unbiased estimate of the antiquity of lineages relevant to the genetic history of the human Y chromosome. In particular, the two deepest nodes of the tree highlight the survival, in Central-Western Africa, of lineages whose coalescence (291 ky, 95% C.I. 253-343) predates the emergence of anatomically modern features in the fossil record. PMID:26226630

  14. Regional Differences in the Accumulation of SNPs on the Male-Specific Portion of the Human Y Chromosome Replicate Autosomal Patterns: Implications for Genetic Dating

    PubMed Central

    Trombetta, Beniamino; D'Atanasio, Eugenia; Massaia, Andrea; Myres, Natalie M.; Scozzari, Rosaria; Cruciani, Fulvio; Novelletto, Andrea

    2015-01-01

    Factors affecting the rate and pattern of the mutational process are being identified for human autosomes, but the same relationships for the male specific portion of the Y chromosome (MSY) are not established. We considered 3,390 mutations occurring in 19 sequence bins identified by sequencing 1.5 Mb of the MSY from each of 104 present-day chromosomes. The occurrence of mutations was not proportional to the amount of sequenced bases in each bin, with a 2-fold variation. The regression of the number of mutations per unit sequence against a number of indicators of the genomic features of each bin, revealed the same fundamental patterns as in the autosomes. By considering the sequences of the same region from two precisely dated ancient specimens, we obtained a calibrated region-specific substitution rate of 0.716 × 10-9/site/year. Despite its lack of recombination and other peculiar features, the MSY then resembles the autosomes in displaying a marked regional heterogeneity of the mutation rate. An immediate implication is that a given figure for the substitution rate only makes sense if bound to a specific DNA region. By strictly applying this principle we obtained an unbiased estimate of the antiquity of lineages relevant to the genetic history of the human Y chromosome. In particular, the two deepest nodes of the tree highlight the survival, in Central-Western Africa, of lineages whose coalescence (291 ky, 95% C.I. 253–343) predates the emergence of anatomically modern features in the fossil record. PMID:26226630

  15. Multiplex PCR based screening for micro/partial deletions in the AZF region of Y-chromosome in severe oligozoospermic and azoospermic infertile men in Iran

    PubMed Central

    Motovali-Bashi, Majid; Rezaei, Zahra; Dehghanian, Fariba; Rezaei, Halimeh

    2015-01-01

    Background: Infertility is a health problem which affects about 10-20% of married couples. Male factor infertility is involved approximately 50% of infertile couples. Most of male infertility is regarding to deletions in the male-specific region of the Y chromosome. Objective: In this study, the occurrence of deletions in the AZF region and association between infertility and paternal age were investigated in Iranian men population. Materials and Methods: To assess the occurrence of Y chromosomal microdeletions and partial deletions of the AZF region, 100 infertile men and 100 controls with normal spermatogenesis were analyzed. AZFa, AZFb, AZFc and partial deletions within the AZFc region were analyzed using multiplex PCR method. Finally, the association between paternal age and male infertility was evaluated. Results: No AZFa, AZFb or AZFc deletions were found in the control group. Seven infertile men had deletions as the following: one AZFb, five AZFc, and one AZFab. Partial deletions of AZFc (gr/gr) in 9 of the 100 infertile men (9/100, 9%) and 1 partial AZFc deletions (gr/gr) in the control group (1/100, 1%) were observed. In addition, five b2/b3 deletions in five azoospermic subjects (5/100, 5%) and 2 partial AZFc deletions (b2/b3) in the control group (2/100, 2%) were identified. Moreover, the risk of male infertility was influenced by the paternal age. Conclusion: The results of this study suggested that the frequency of Y chromosome AZF microdeletions increased in subjects with severe spermatogenic failure and gr/gr deletion associated with spermatogenic failure. PMID:26568761

  16. Polymorphism, duplication, and IS1-mediated rearrangement in the chromosomal his-rfb-gnd region of Escherichia coli strains with group IA and capsular K antigens.

    PubMed

    Drummelsmith, J; Amor, P A; Whitfield, C

    1997-05-01

    Individual Escherichia coli strains produce several cell surface polysaccharides. In E. coli E69, the his region of the chromosome contains the rfb (serotype O9 lipopolysaccharide O-antigen biosynthesis) and cps (serotype K30 group IA capsular polysaccharide biosynthesis) loci. Polymorphisms in this region of the Escherichia coli chromosome reflect extensive antigenic diversity in the species. Previously, we reported a duplication of the manC-manB genes, encoding enzymes involved in GDP-mannose formation, upstream of rfb in strain E69 (P. Jayaratne et al., J. Bacteriol. 176:3126-3139, 1994). Here we show that one of the manC-manB copies is flanked by IS1 elements, providing a potential mechanism for the gene duplication. Adjacent to manB1 on the IS1-flanked segment is a further open reading frame (ugd), encoding uridine-5'-diphosphoglucose dehydrogenase. The Ugd enzyme is responsible for the production of UDP-glucuronic acid, a precursor required for K30 antigen synthesis. Construction of a chromosomal ugd::Gm(r) insertion mutation demonstrated the essential role for Ugd in the biosynthesis of the K30 antigen and confirmed that there is no additional functional ugd copy in strain E69. PCR amplification and Southern hybridization were used to examine the distribution of IS1 elements and ugd genes in the vicinity of rfb in other E. coli strains, producing different group IA K antigens. The relative order of genes and, where present, IS1 elements was established in these strains. The regions adjacent to rfb in these strains are highly variable in both size and gene order, but in all cases where a ugd homolog was present, it was found near rfb. The presence of IS1 elements in the rfb regions of several of these strains provides a potential mechanism for recombination and deletion events which could contribute to the antigenic diversity seen in surface polysaccharides. PMID:9150218

  17. Genetic mapping of the branchio-oto-renal syndrome and construction of YAC contig spanning the BOR region on chromosome 8q

    SciTech Connect

    Kumar, S.; Kimberling, W.J.; Bumegi, J.

    1994-09-01

    Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder which consists of external, middle and inner ear malformations, branchial cleft sinuses, cervical fistulas, mixed hearing loss and renal anomalies. The prevalence of BOR syndrome is approximately 1:40,000, and it has been reported to occur in about 2% of profoundly deaf children. The BOR syndrome has been localized to chromosome 8q. Initial localization results indicated a distance of about 15 cM between the flanking markers D8S87 and PENK for the BOR gene. This localization has been further refined, using new markers, to a distance of about 7 cM. The multipoint analysis was carried out using markers D8S285, PENK, D8S166, D8S260, D8S510, D8S553, D8S543, D8S530, D8S279, D8S164, D8S286 and D8S275. For cloning the BOR gene, an overlapping Yeast Artificial Chromosome (YAC) contig map of the critical region is being constructed. We have isolated eight YACs from the CEPH Mega YAC library and their size and quality are being characterized by PFGE and FISH analysis. Additional STSs and polymorphic markers developed from the region will be used to further refine the region and close the contig. The availability of this contig will be a useful resource for the systematic search for identifying transcribed sequences from this region.

  18. Origin and domestication of papaya Yh chromosome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. Methods for chromosome-specific staining

    DOEpatents

    Gray, Joe W.; Pinkel, Daniel

    1995-01-01

    Methods and compositions for chromosome-specific staining are provided. Compositions comprise heterogenous mixtures of labeled nucleic acid fragments having substantially complementary base sequences to unique sequence regions of the chromosomal DNA for which their associated staining reagent is specific. Methods include methods for making the chromosome-specific staining compositions of the invention, and methods for applying the staining compositions to chromosomes.

  20. Single nucleotide polymorphisms in an STS region linked to the Ncc-tmp1A locus are informative for characterizing the differentiation of chromosome 1A in wheat.

    PubMed

    Asakura, N; Mori, N; Ishido, T; Ohtsuka, I; Nakamura, C

    2001-10-01

    Homoeoalleles of Ncc confer nucleus-cytoplasm (NC) compatibility on NC hybrids of wheat with the D plasmon of Aegilops squarrosa. To dissect the chromosomal region containing Ncc, a RAPD marker linked to the Ncc-tmplA locus, which is located on chromosome 1A of T timopheevi, was sequenced and converted to a PCR-based sequence-tagged-site (STS) marker. Five single nucleotide polymorphisms (SNPs) between T timopheevi and T turgidum. were detected in a 509-bp genomic DNA fragment. Based on the SNPs, the STS alleles in 164 accessions from emmer wheat, timopheevi wheat and two einkorn wheats, T. urartu and T. boeoticum were surveyed by PCR-RFLP analysis. The sequence comparisons and PCR-RFLP analyses revealed nine alleles based on six SNPs. These SNPs were highly conserved within each group of wheat, and all groups could be distinguished by particular combinations of the SNPs. All accessions of T. urartu had one unique STS allele as compared with the others. Our results indicate that the SNPs in the STS marker linked to the Ncc-tmplA locus would be informative for studies of the differentiation of chromosome 1A in wheat. PMID:11817645

  1. Genetic mapping of a locus for multiple ephiphyseal dysplasia (EDM2) to a region of chromosome 1 containing a type IX collagen gene

    SciTech Connect

    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.

    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.

  2. Restriction maps of the regions coding for methicillin and tobramycin resistances on chromosomal DNA in methicillin-resistant staphylococci.

    PubMed Central

    Ubukata, K; Nonoguchi, R; Matsuhashi, M; Song, M D; Konno, M

    1989-01-01

    Chromosomal BamHI DNA fragments containing both the mecA gene encoding the penicillin-binding protein responsible for methicillin resistance and the aadD gene encoding 4',4"-adenylyltransferase responsible for tobramycin resistance were cloned from three methicillin- and tobramycin-resistant strains of Staphylococcus aureus and one strain of Staphylococcus epidermidis. Physical maps of the fragments were similar, suggesting their unique origin. Images PMID:2817861

  3. Chromosome aberrations in human lymphocytes from the plateau region of the Bragg curve for a carbon-ion beam

    NASA Astrophysics Data System (ADS)

    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.

  4. Characterization of chromosomal architecture in Arabidopsis by chromosome conformation capture

    PubMed Central

    2013-01-01

    Background The packaging of long chromatin fibers in the nucleus poses a major challenge, as it must fulfill both physical and functional requirements. Until recently, insights into the chromosomal architecture of plants were mainly provided by cytogenetic studies. Complementary to these analyses, chromosome conformation capture technologies promise to refine and improve our view on chromosomal architecture and to provide a more generalized description of nuclear organization. Results Employing circular chromosome conformation capture, this study describes chromosomal architecture in Arabidopsis nuclei from a genome-wide perspective. Surprisingly, the linear organization of chromosomes is reflected in the genome-wide interactome. In addition, we study the interplay of the interactome and epigenetic marks and report that the heterochromatic knob on the short arm of chromosome 4 maintains a pericentromere-like interaction profile and interactome despite its euchromatic surrounding. Conclusion Despite the extreme condensation that is necessary to pack the chromosomes into the nucleus, the Arabidopsis genome appears to be packed in a predictive manner, according to the following criteria: heterochromatin and euchromatin represent two distinct interactomes; interactions between chromosomes correlate with the linear position on the chromosome arm; and distal chromosome regions have a higher potential to interact with other chromosomes. PMID:24267747

  5. Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17

    SciTech Connect

    Tomasetto, C.; Regnier, C.; Basset, P.

    1995-08-10

    We have performed differential screening of a human metastatic lymph node cDNA library to identify genes possibly involved during breast cancer progression. We have identified four novel genes overexpressed in malignant tissues. They were all located between q11 and q21.3, a region known to contain the c-erbB-2 oncogene and the BRCA1 breast carcinomas, and overexpression of three of them was dependent on gene amplification in breast cancer cell lines. These findings further support the concept that human chromosome 17 specifically carries genes possibly involved in breast cancer progression. 61 refs., 3 figs., 4 tabs.

  6. A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States.

    PubMed

    Francks, Clyde; Paracchini, Silvia; Smith, Shelley D; Richardson, Alex J; Scerri, Tom S; Cardon, Lon R; Marlow, Angela J; MacPhie, I Laurence; Walter, Janet; Pennington, Bruce F; Fisher, Simon E; Olson, Richard K; DeFries, John C; Stein, John F; Monaco, Anthony P

    2004-12-01

    Several quantitative trait loci (QTLs) that influence developmental dyslexia (reading disability [RD]) have been mapped to chromosome regions by linkage analysis. The most consistently replicated area of linkage is on chromosome 6p23-21.3. We used association analysis in 223 siblings from the United Kingdom to identify an underlying QTL on 6p22.2. Our association study implicates a 77-kb region spanning the gene TTRAP and the first four exons of the neighboring uncharacterized gene KIAA0319. The region of association is also directly upstream of a third gene, THEM2. We found evidence of these associations in a second sample of siblings from the United Kingdom, as well as in an independent sample of twin-based sibships from Colorado. One main RD risk haplotype that has a frequency of approximately 12% was found in both the U.K. and U.S. samples. The haplotype is not distinguished by any protein-coding polymorphisms, and, therefore, the functional variation may relate to gene expression. The QTL influences a broad range of reading-related cognitive abilities but has no significant impact on general cognitive performance in these samples. In addition, the QTL effect may be largely limited to the severe range of reading disability. PMID:15514892

  7. Localization of a breast cancer tumour-suppressor gene to a 3-cM interval within chromosomal region 16q22.

    PubMed

    Iida, A; Isobe, R; Yoshimoto, M; Kasumi, F; Nakamura, Y; Emi, M

    1997-01-01

    Allelic losses on chromosome 16q in tumour cells are frequent in a variety of malignancies, suggesting the presence of one or more tumour-suppressor genes in the region. Among 210 sporadic breast cancers we examined using 15 microsatellite markers on the long arm of chromosome 16, heterozygosity for at least one locus was lost in 141 (67%). Detailed deletion mapping revealed two distinct commonly deleted regions. One region was defined as a 3-cM interval flanked by markers D16S512 and D16S515 at 16q22; the second consisted of a 9.5-cM interval flanked by markers D16S498 and D16S303 at q24.3. Allelic loss on 16q was observed frequently in small tumours, tumours without lymph node metastasis and tumours of the non-invasive histological type as well as in tumours of more advanced phenotype, suggesting that inactivation of one of at least two tumour-suppressor genes on 16q plays a role in early stage breast carcinogenesis. PMID:9010036

  8. A complete YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13) and refined localization of the SNRPN gene

    SciTech Connect

    Mutirangura, A.; Jayakumar, A.; Sutcliffe, J.S.; Nakao, M.; McKinney, M.J.; Beaudet, A.L.; Chinault, A.C.; Ledbetter, D.H. ); Buiting, K.; Horsthemke, B. )

    1993-12-01

    Since a previous report of a partial YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13), a complete contig spanning approximately 3.5 Mb has been developed. YACs were isolated from two human genomic libraries by PCR and hybridization screening methods. Twenty-three sequence-tagged sites (STSs) were mapped within the contig, a density of [approximately]1 per 200 kb. Overlaps between YAC clones were identified by Alu-PCR dot-blot analysis and confirmed by STS mapping or hybridization with ends of YAC inserts. The gene encoding small nuclear ribonucleoprotein-associated peptide N (SNRPN), recently identified as a candidate gene for Prader-Willi syndrome, was localized within this contig between markers PW71 and TD3-21. Loci mapped within and immediately flanking the Prader-Willi/Angelman chromosome region contig are ordered as follows: cen-IR39-ML34-IR4-3R-TD189-1-PW71-SNRPN-TD3-21-LS6-1-GABRB3,D15S97-GABRA5-IR10-1-CMW1-tel. This YAC contig will be a useful resource for more detailed physical mapping of the region, for generation of new DNA markers, and for mapping or cloning candidate genes for the Prader-Willi and Angelman syndromes. 36 refs., 2 figs., 2 tabs.

  9. Isolation and analysis of a novel gene, HXC-26, adjacent to the rab GDP dissociation inhibitor gene located at human chromosome Xq28 region.

    PubMed

    Toyoda, A; Sakai, T; Sugiyama, Y; Kusuda, J; Hashimoto, K; Maeda, H

    1996-10-31

    We screened potential promoter regions from NotI-linking cosmid clones mapped on human chromosome Xq28 region with our constructed trapping vector and isolated six fragments containing transcription activity. Using one of the obtained fragments as a probe, a novel gene was isolated by screening a human skeletal muscle cDNA library. The isolated cDNA, termed HXC-26, contained an open reading frame of 975 nucleotides encoding 325 amino acids (38,848 Da). The HXC-26 gene was composed of 13 exons that span approximately 8 kb. Several potential GC boxes were found in the putative promoter region, but no typical TATA box. The HXC-26 gene associated with a CpG island was located adjacent to the rab GDP dissociation inhibitor (GDI) gene. PMID:9039504

  10. Identification of the Ω4406 Regulatory Region, a Developmental Promoter of Myxococcus xanthus, and a DNA Segment Responsible for Chromosomal Position-Dependent Inhibition of Gene Expression

    PubMed Central

    Loconto, Jennifer; Viswanathan, Poorna; Nowak, Scott J.; Gloudemans, Monica; Kroos, Lee

    2005-01-01

    When starved, Myxococcus xanthus cells send signals to each other that coordinate their movements, gene expression, and differentiation. C-signaling requires cell-cell contact, and increasing contact brought about by cell alignment in aggregates is thought to increase C-signaling, which induces expression of many genes, causing rod-shaped cells to differentiate into spherical spores. C-signaling involves the product of the csgA gene. A csgA mutant fails to express many genes that are normally induced after about 6 h into the developmental process. One such gene was identified by insertion of Tn5 lac at site Ω4406 in the M. xanthus chromosome. Tn5 lac fused transcription of lacZ to the upstream Ω4406 promoter. In this study, the Ω4406 promoter region was identified by analyzing mRNA and by testing different upstream DNA segments for the ability to drive developmental lacZ expression in M. xanthus. The 5′ end of Ω4406 mRNA mapped to approximately 1.3 kb upstream of the Tn5 lac insertion. A 1.0-kb DNA segment from 0.8 to 1.8 kb upstream of the Tn5 lac insertion, when fused to lacZ and integrated at a phage attachment site in the M. xanthus chromosome, showed a similar pattern of developmental expression as Tn5 lac Ω4406. The DNA sequence upstream of the putative transcriptional start site was strikingly similar to promoter regions of other C-signal-dependent genes. Developmental lacZ expression from the 1.0-kb segment was abolished in a csgA mutant but was restored upon codevelopment of the csgA mutant with wild-type cells, which supply C-signal, demonstrating that the Ω4406 promoter responds to extracellular C-signaling. Interestingly, the 0.8-kb DNA segment immediately upstream of Tn5 lac Ω4406 inhibited expression of a downstream lacZ reporter in transcriptional fusions integrated at a phage attachment site in the chromosome but not at the normal Ω4406 location. To our knowledge, this is the first example in M. xanthus of a chromosomal position

  11. Amplification of chromosomal DNA in situ

    DOEpatents

    Christian, Allen T.; Coleman, Matthew A.; Tucker, James D.

    2002-01-01

    Amplification of chromosomal DNA in situ to increase the amount of DNA associated with a chromosome or chromosome region is described. The amplification of chromosomal DNA in situ provides for the synthesis of Fluorescence in situ Hybridization (FISH) painting probes from single dissected chromosome fragments, the production of cDNA libraries from low copy mRNAs and improved in Comparative Genomic Hybridization (CGH) procedures.

  12. Genomic analysis of a 1 Mb region near the telomere of Hessian fly chromosome X2 and avirulence gene vH13

    PubMed Central

    Lobo, Neil F; Behura, Susanta K; Aggarwal, Rajat; Chen, Ming-Shun; Collins, Frank H; Stuart, Jeff J

    2006-01-01

    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. PMID:16412254

  13. A novel repetitive sequence, termed the JNK repeat family, located on an extra heterochromatic region of chromosome 2R of Japanese rye.

    PubMed

    Nagaki, K; Tsujimoto, H; Sasakuma, T

    1999-01-01

    Among cultivated rye, Seccale cereale L., collected in Japan, we found an extra heterochromatin on the long-arm interstitial region of chromosome 2R. This extra heterochromatin was polymorphic in the population. The plants with the extra heterochromatin showed a specific DNA fragment of 1.2 kb in digests prepared with the restriction enzyme Dral. The fragment was cloned and used as a probe for fluorescent in-situ hybridization (FISH). The clone, pScJNK1, showed a hybridization signal at the extra heterochromatic region. The segregation of the number of signals corresponded to the number of the extra heterochromatin of the 2R chromosome, indicating that the sequence might construct the heterochromatin. Southern hybridization using the clone as a probe showed a ladder pattern, suggesting that the sequence was a tandem repeat. Three sequences homologous to pScJNK1 were isolated; these were 1192 1232 bp, 44.7-45.9% in GC content, highly homologous (> 93%) with each other, and did not show any significant homology to other sequences in a DNA database. Slot blot hybridization using pScJNK1 as a probe indicated that there were about 4000 copies of the sequence in the haploid genome carrying the extra heterochromatin, whereas less than 20 copies existed in the genome without the heterochromatin. Southern hybridization using MspI and HapII indicated that all of the second cytosine nucleotides in CCGG sites in the sequence were methylated in the extra heterochromatin. PMID:10328621

  14. Pericentromeric Regions of Soybean (Glycine max L. Merr.) Chromosomes Consist of Retroelements and Tandemly Repeated DNA and Are Structurally and Evolutionarily Labile

    PubMed Central

    Lin, Jer-Young; Jacobus, Barbara Hass; SanMiguel, Phillip; Walling, Jason G.; Yuan, Yinan; Shoemaker, Randy C.; Young, Nevin D.; Jackson, Scott A.

    2005-01-01

    Little is known about the physical makeup of heterochromatin in the soybean (Glycine max L. Merr.) genome. Using DNA sequencing and molecular cytogenetics, an initial analysis of the repetitive fraction of the soybean genome is presented. BAC 076J21, derived from linkage group L, has sequences conserved in the pericentromeric heterochromatin of all 20 chromosomes. FISH analysis of this BAC and three subclones on pachytene chromosomes revealed relatively strict partitioning of the heterochromatic and euchromatic regions. Sequence analysis showed that this BAC consists primarily of repetitive sequences such as a 102-bp tandem repeat with sequence identity to a previously characterized ∼120-bp repeat (STR120). Fragments of Calypso-like retroelements, a recently inserted SIRE1 element, and a SIRE1 solo LTR were present within this BAC. Some of these sequences are methylated and are not conserved outside of G. max and G. soja, a close relative of soybean, except for STR102, which hybridized to a restriction fragment from G. latifolia. These data present a picture of the repetitive fraction of the soybean genome that is highly concentrated in the pericentromeric regions, consisting of rapidly evolving tandem repeats with interspersed retroelements.

  15. Deletion and duplication at DYS448 and DYS626 loci: unexpected patterns within the AZFc region of the Y-chromosome.

    PubMed

    Turrina, Stefania; Caratti, Stefano; Ferrian, Melissa; De Leo, Domenico

    2015-05-01

    Increasing the knowledge of multiple and microstructural events within the Y-chromosome may prove useful to better characterize abnormal short tandem repeats patterns complicating DNA profile interpretation. On the long arm of the human Y-chromosome, such structural rearrangements were observed in azoospermia factor regions (AZFa, AZFb, AZFc) that play an important role in male fertility and also host Y-STRs commonly used in forensic genetics. Here, we describe two cases, involving two males formerly included in an Italian population study, where DYS448 and DYS626 loci, located within the AZFc region, simultaneously displayed a double deletion in one case and a double duplication in the other. With the aim of better defining the size of both events, low and high-resolution mapping by means of 16 sequence-tagged sites was performed, and unexpected discontinued patterns within the palindromic segments b1/b3 of the AZFc were identified. Extending the analysis to their respective male relatives revealed unaltered transmission of the patterns along the two pedigrees. Reviewing literature data describing DYS448-DYS626 deletion and duplication suggested no close correlation between the occurrence of multiple/microstructural events and geographical origin. PMID:25821202

  16. The nuclear protein encoded by the Drosophila neurogenic gene mastermind is widely expressed and associates with specific chromosomal regions

    SciTech Connect

    Bettler, D.; Pearson, S.; Yedvobnick, B.

    1996-06-01

    The Drosophila neurogenic loci encode a diverse group of proteins that comprise an inhibitory signal transduction pathway. The pathway is used throughout development in numerous contexts. We have examined the distribution of the neurogenic locus mastermind protein (Mam). Mam is expressed through all germlayers during early embryogenesis, including ectodermal precursors to both neuroblasts and epidermoblasts. Mam is subsequently down-regulated within the nervous system and then reexpressed. It persists in the nervous system through late embryogenesis and postembryonically. Mam is ubiquitously expressed in wing and leg imaginal discs and is not down-regulated in sensory organ precursor cells of the wing margin or notum. In the eye disc, Mam shows most prominent expression posterior to the morphogenetic furrow. Expression of the protein during oogenesis appears limited to follicle cells. Immunohistochemical detection of Mam on polytene chromosomes revealed binding at >100 sites. Chromosome colocalization studies with RNA polymerase and the groucho corepressor protein implicate Mam in transcriptional regulation. 94 refs., 8 figs., 1 tab.

  17. Identification of random nucleic acid sequence aberrations using dual capture probes which hybridize to different chromosome regions

    DOEpatents

    Lucas, Joe N.; Straume, Tore; Bogen, Kenneth T.

    1998-01-01

    A method is provided for detecting nucleic acid sequence aberrations using two immobilization steps. According to the method, a nucleic acid sequence aberration is detected by detecting nucleic acid sequences having both a first nucleic acid sequence type (e.g., from a first chromosome) and a second nucleic acid sequence type (e.g., from a second chromosome), the presence of the first and the second nucleic acid sequence type on the same nucleic acid sequence indicating the presence of a nucleic acid sequence aberration. In the method, immobilization of a first hybridization probe is used to isolate a first set of nucleic acids in the sample which contain the first nucleic acid sequence type. Immobilization of a second hybridization probe is then used to isolate a second set of nucleic acids from within the first set of nucleic acids which contain the second nucleic acid sequence type. The second set of nucleic acids are then detected, their presence indicating the presence of a nucleic acid sequence aberration.

  18. Identification of random nucleic acid sequence aberrations using dual capture probes which hybridize to different chromosome regions

    DOEpatents

    Lucas, J.N.; Straume, T.; Bogen, K.T.

    1998-03-24

    A method is provided for detecting nucleic acid sequence aberrations using two immobilization steps. According to the method, a nucleic acid sequence aberration is detected by detecting nucleic acid sequences having both a first nucleic acid sequence type (e.g., from a first chromosome) and a second nucleic acid sequence type (e.g., from a second chromosome), the presence of the first and the second nucleic acid sequence type on the same nucleic acid sequence indicating the presence of a nucleic acid sequence aberration. In the method, immobilization of a first hybridization probe is used to isolate a first set of nucleic acids in the sample which contain the first nucleic acid sequence type. Immobilization of a second hybridization probe is then used to isolate a second set of nucleic acids from within the first set of nucleic acids which contain the second nucleic acid sequence type. The second set of nucleic acids are then detected, their presence indicating the presence of a nucleic acid sequence aberration. 14 figs.

  19. Assignment of Ptprn2, the gene encoding receptor-type protein tyrosine phosphatase IA-2beta, a major autoantigen in insulin-dependent diabetes mellitus, to mouse chromosome region 12F.

    PubMed

    van den Maagdenberg, A M; Schepens, J T; Schepens, M T; Pepers, B; Wieringa, B; van Kessel, A G; Hendriks, W J

    1998-01-01

    The receptor-type protein tyrosine phosphatase IA-2beta gene (mouse gene symbol Ptprn2) encodes a major autoantigen in insulin-dependent diabetes mellitus. We physically mapped Ptprn2 by fluorescence in situ hybridization to band F of mouse chromosome 12, a region that lacks diabetes susceptibility loci. The mapping confirms the proposed synteny of mouse 12F with band q36 of human chromosome 7. PMID:9858807

  20. SNPs detection in DHPS-WDR83 overlapping genes mapping on porcine chromosome 2 in a QTL region for meat pH

    PubMed Central

    2013-01-01

    Background The pH is an important parameter influencing technological quality of pig meat, a trait affected by environmental and genetic factors. Several quantitative trait loci associated to meat pH are described on PigQTL database but only two genes influencing this parameter have been so far detected: Ryanodine receptor 1 and Protein kinase, AMP-activated, gamma 3 non-catalytic subunit. To search for genes influencing meat pH we analyzed genomic regions with quantitative effect on this trait in order to detect SNPs to use for an association study. Results The expressed sequences mapping on porcine chromosomes 1, 2, 3 in regions associated to pork pH were searched in silico to find SNPs. 356 out of 617 detected SNPs were used to genotype Italian Large White pigs and to perform an association analysis with meat pH values recorded in semimembranosus muscle at about 1 hour (pH1) and 24 hours (pHu) post mortem. The results of the analysis showed that 5 markers mapping on chromosomes 1 or 3 were associated with pH1 and 10 markers mapping on chromosomes 1 or 2 were associated with pHu. After False Discovery Rate correction only one SNP mapping on chromosome 2 was confirmed to be associated to pHu. This polymorphism was located in the 3’UTR of two partly overlapping genes, Deoxyhypusine synthase (DHPS) and WD repeat domain 83 (WDR83). The overlapping of the 3’UTRs allows the co-regulation of mRNAs stability by a cis-natural antisense transcript method of regulation. DHPS catalyzes the first step in hypusine formation, a unique amino acid formed by the posttranslational modification of the protein eukaryotic translation initiation factor 5A in a specific lysine residue. WDR83 has an important role in the modulation of a cascade of genes involved in cellular hypoxia defense by intensifying the glycolytic pathway and, theoretically, the meat pH value. Conclusions The involvement of the SNP detected in the DHPS/WDR83 genes on meat pH phenotypic variability and their

  1. A 725 kb deletion at 22q13.1 chromosomal region including SOX10 gene in a boy with a neurologic variant of Waardenburg syndrome type 2.

    PubMed

    Siomou, Elisavet; Manolakos, Emmanouil; Petersen, Michael; Thomaidis, Loretta; Gyftodimou, Yolanda; Orru, Sandro; Papoulidis, Ioannis

    2012-11-01

    Waardenburg syndrome (WS) is a rare (1/40,000) autosomal dominant disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four clinical subtypes (WS1-S4). Six genes have been identified to be associated with the different subtypes of WS, among which SOX10, which is localized within the region 22q13.1. Lately it has been suggested that whole SOX10 gene deletions can be encountered when testing for WS. In this study we report a case of a 13-year-old boy with a unique de novo 725 kb deletion within the 22q13.1 chromosomal region, including the SOX10 gene and presenting clinical features of a neurologic variant of WS2. PMID:22842075

  2. A gene in the chromosomal region 3p21 with greatly reduced expression in lung cancer is similar to the gene for ubiquitin-activating enzyme.

    PubMed Central

    Kok, K; Hofstra, R; Pilz, A; van den Berg, A; Terpstra, P; Buys, C H; Carritt, B

    1993-01-01

    The chromosomal region 3p21 is thought to be the site of a lung tumor suppressor gene. We recently cloned a gene from this region that has greatly reduced expression in almost all lung tumor cell lines examined, in spite of being widely expressed in a variety of other tumor and nontumor cell types. We report here the sequence of this gene and show that it has significant homology to the genes encoding the ubiquitin-activating enzymes of three species, including humans. This suggests it is a second, autosomal member of this gene family in humans and may play a role in the ubiquitin conjugation pathway, which is of central importance in all eukaryotes. PMID:8327486

  3. A radiation hybrid map of 15 loci on the distal long arm of chromosome 4, the region containing the gene responsible for facioscapulohumeral muscular dystrophy (FSHD)

    SciTech Connect

    Winokur, S.T.; Wasmuth, J.H. ); Schutte, B. ); Weiffenbach, B. ); Washington, S.S.; Chakravarti, A. ); McElligot, D. ); Altherr, M.R. Los Alamos National Lab., NM )

    1993-10-01

    A physical map of 4q35 was constructed through radiation hybrid analysis of 134 clones generated from the cell line HHW416, a chromosome 4-only human-hamster somatic cell hybrid. This subtelomeric region contains the as-yet-unidentified gene responsible for facioscapulohumeral muscular dystrophy. The most likely order of 15 loci within 4q35 was determined. The loci ordered on this radiation hybrid map include both genes and polymorphic loci, as well as monomorphic loci which cannot be placed on a genetic linkage map. The physical distance spanning these loci was estimated to be approximately 4.5 Mb, by using a kilobase/centiray conversion factor derived from 4p16.3 marker analysis through the same set of radiation hybrids. The comparison of this physical map to established genetic maps suggests that this region is smaller than initially estimated and that recombination rates are increased near the telomere. 37 refs., 2 figs., 2 tabs.

  4. A cloned DNA segment from the telomeric region of human chromosome 4p is not detectably rearranged in Huntington disease patients.

    PubMed Central

    Pritchard, C; Casher, D; Bull, L; Cox, D R; Myers, R M

    1990-01-01

    Genetic linkage studies have mapped the Huntington disease (HD) mutation to the distal region of the short arm of human chromosome 4. Analysis of recombination events in this region has produced contradictory locations for HD. One possible location is in the region distal to the D4S90 marker, which is located within 300 kilobases of the telomere. Other crossover events predict a more centromeric position for HD. Here we analyze the telomeric region of 4p in detail. Cloned DNA segments were derived from this region by utilizing a radiation-induced somatic cell hybrid as a source of DNA combined with preparative pulsed-field gel electrophoresis to enrich for the telomeric fraction. Additional DNA was obtained by using the cloned segments as multiple start points for cosmid walks. This strategy proved to be an effective method for cloning 250 kilobases of DNA in the region telomeric to D4S90. Hybridization analysis with the cloned DNA did not provide any evidence for the presence of rearrangements of 100 base pairs or greater in the DNA of individuals affected with HD. We also found no change in the size or structure of the 4p telomere in these samples. Images PMID:2144903

  5. A cloned DNA segment from the telomeric region of human chromosome 4p is not detectably rearranged in Huntington disease patients.

    PubMed

    Pritchard, C; Casher, D; Bull, L; Cox, D R; Myers, R M

    1990-09-01

    Genetic linkage studies have mapped the Huntington disease (HD) mutation to the distal region of the short arm of human chromosome 4. Analysis of recombination events in this region has produced contradictory locations for HD. One possible location is in the region distal to the D4S90 marker, which is located within 300 kilobases of the telomere. Other crossover events predict a more centromeric position for HD. Here we analyze the telomeric region of 4p in detail. Cloned DNA segments were derived from this region by utilizing a radiation-induced somatic cell hybrid as a source of DNA combined with preparative pulsed-field gel electrophoresis to enrich for the telomeric fraction. Additional DNA was obtained by using the cloned segments as multiple start points for cosmid walks. This strategy proved to be an effective method for cloning 250 kilobases of DNA in the region telomeric to D4S90. Hybridization analysis with the cloned DNA did not provide any evidence for the presence of rearrangements of 100 base pairs or greater in the DNA of individuals affected with HD. We also found no change in the size or structure of the 4p telomere in these samples. PMID:2144903

  6. Assignment of three human markers in chromosome 21q11 to mouse chromosome 16.

    PubMed

    Yu, J; Shen, Y; Tong, S; Kao, F T

    1997-09-01

    Three unique sequence microclones from human chromosome region 21q11 were assigned to mouse chromosome 16 using a mouse/Chinese hamster cell hybrid 96Az2 containing a single mouse chromosome 16. This comparative mapping provides further homology between human chromosome 21 and mouse chromosome 16 to include the very proximal portion of the long arm of human chromosome 21. Since this part of human chromosome 21 is associated with mental retardation in Down syndrome individuals, its homologous mouse region should also be included in the construction of mouse models for studying Down syndrome phenotypes including mental retardation. PMID:9546078

  7. Evidence for positive selection of taurine genes within a QTL region on chromosome X associated with testicular size in Australian Brahman cattle

    PubMed Central

    2014-01-01

    Background Previous genome-wide association studies have identified significant regions of the X chromosome associated with reproductive traits in two Bos indicus-influenced breeds: Brahman cattle and Tropical Composites. Two QTL regions on this chromosome were identified in both breeds as strongly associated with scrotal circumference measurements, a reproductive trait previously shown to be useful for selection of young bulls. Scrotal circumference is genetically correlated with early age at puberty in both male and female offspring. These QTL were located at positions 69–77 and 81–92 Mb respectively, large areas each to which a significant number of potential candidate genes were mapped. Results To further characterise these regions, a bioinformatic approach was undertaken to identify novel non-synonymous SNP within the QTL regions of interest in Brahman cattle. After SNP discovery, we used conventional molecular assay technologies to perform studies of two candidate genes in both breeds. Non-synonymous SNP mapped to Testis-expressed gene 11 (Tex11) were associated (P < 0.001) with scrotal circumference in both breeds, and associations with percentage of normal sperm cells were also observed (P < 0.05). Evidence for recent selection was found as Tex11 SNP form a haplotype segment of Bos taurus origin that is retained within Brahman and Tropical Composite cattle with greatest reproductive potential. Conclusions Association of non-synonymous SNP presented here are a first step to functional genetic studies. Bovine species may serve as a model for studying the role of Tex11 in male fertility, warranting further in-depth molecular characterisation. PMID:24410912

  8. Chimeric Sex-Determining Chromosomal Regions and Dysregulation of Cell-Type Identity in a Sterile Zygosaccharomyces Allodiploid Yeast.

    PubMed

    Bizzarri, Melissa; Giudici, Paolo; Cassanelli, Stefano; Solieri, Lisa

    2016-01-01

    Allodiploidization is a fundamental yet evolutionarily poorly characterized event, which impacts genome evolution and heredity, controlling organismal development and polyploid cell-types. In this study, we investigated the sex determination system in the allodiploid and sterile ATCC 42981 yeast, a member of the Zygosaccharomyces rouxii species complex, and used it to study how a chimeric mating-type gene repertoire contributes to hybrid reproductive isolation. We found that ATCC 42981 has 7 MAT-like (MTL) loci, 3 of which encode α-idiomorph and 4 encode a-idiomorph. Two phylogenetically divergent MAT expression loci were identified on different chromosomes, accounting for a hybrid a/α genotype. Furthermore, extra a-idimorph-encoding loci (termed MTLa copies 1 to 3) were recognized, which shared the same MATa1 ORFs but diverged for MATa2 genes. Each MAT expression locus was linked to a HML silent cassette, while the corresponding HMR loci were located on another chromosome. Two putative parental sex chromosome pairs contributed to this unusual genomic architecture: one came from an as-yet-undescribed taxon, which has the NCYC 3042 strain as a unique representative, while the other did not match any MAT-HML and HMR organizations previously described in Z. rouxii species. This chimeric rearrangement produces two copies of the HO gene, which encode for putatively functional endonucleases essential for mating-type switching. Although both a and α coding sequences, which are required to obtain a functional cell-type a1-α2 regulator, were present in the allodiploid ATCC 42981 genome, the transcriptional circuit, which regulates entry into meiosis in response to meiosis-inducing salt stress, appeared to be turned off. Furthermore, haploid and α-specific genes, such as MATα1 and HO, were observed to be actively transcribed and up-regulated under hypersaline stress. Overall, these evidences demonstrate that ATCC 42981 is unable to repress haploid α-specific genes and

  9. Chimeric Sex-Determining Chromosomal Regions and Dysregulation of Cell-Type Identity in a Sterile Zygosaccharomyces Allodiploid Yeast

    PubMed Central

    Bizzarri, Melissa; Giudici, Paolo; Cassanelli, Stefano; Solieri, Lisa

    2016-01-01

    Allodiploidization is a fundamental yet evolutionarily poorly characterized event, which impacts genome evolution and heredity, controlling organismal development and polyploid cell-types. In this study, we investigated the sex determination system in the allodiploid and sterile ATCC 42981 yeast, a member of the Zygosaccharomyces rouxii species complex, and used it to study how a chimeric mating-type gene repertoire contributes to hybrid reproductive isolation. We found that ATCC 42981 has 7 MAT-like (MTL) loci, 3 of which encode α-idiomorph and 4 encode a-idiomorph. Two phylogenetically divergent MAT expression loci were identified on different chromosomes, accounting for a hybrid a/α genotype. Furthermore, extra a-idimorph-encoding loci (termed MTLa copies 1 to 3) were recognized, which shared the same MATa1 ORFs but diverged for MATa2 genes. Each MAT expression locus was linked to a HML silent cassette, while the corresponding HMR loci were located on another chromosome. Two putative parental sex chromosome pairs contributed to this unusual genomic architecture: one came from an as-yet-undescribed taxon, which has the NCYC 3042 strain as a unique representative, while the other did not match any MAT-HML and HMR organizations previously described in Z. rouxii species. This chimeric rearrangement produces two copies of the HO gene, which encode for putatively functional endonucleases essential for mating-type switching. Although both a and α coding sequences, which are required to obtain a functional cell-type a1-α2 regulator, were present in the allodiploid ATCC 42981 genome, the transcriptional circuit, which regulates entry into meiosis in response to meiosis-inducing salt stress, appeared to be turned off. Furthermore, haploid and α-specific genes, such as MATα1 and HO, were observed to be actively transcribed and up-regulated under hypersaline stress. Overall, these evidences demonstrate that ATCC 42981 is unable to repress haploid α-specific genes and

  10. Plant Sex Chromosomes.

    PubMed

    Charlesworth, Deborah

    2016-04-29

    Although individuals in most flowering plant species, and in many haploid plants, have both sex functions, dioecious species-in which individuals have either male or female functions only-are scattered across many taxonomic groups, and many species have genetic sex determination. Among these, some have visibly heteromorphic sex chromosomes, and molecular genetic studies are starting to uncover sex-linked markers in others, showing that they too have fully sex-linked regions that are either too small or are located in chromosomes that are too small to be cytologically detectable from lack of pairing, lack of visible crossovers, or accumulation of heterochromatin. Detailed study is revealing that, like animal sex chromosomes, plant sex-linked regions show evidence for accumulation of repetitive sequences and genetic degeneration. Estimating when recombination stopped confirms the view that many plants have young sex-linked regions, making plants of great interest for studying the timescale of these changes. PMID:26653795

  11. Three tumor-suppressor regions on chromosome 11p identified by high-resolution deletion mapping in human non-small-cell lung cancer.

    PubMed Central

    Bepler, G; Garcia-Blanco, M A

    1994-01-01

    Non-small-cell lung cancer is the leading cause of cancer death for men and women in the industrialized nations. Identification of regions for genes involved in its pathogenesis has been difficult. Data presented here show three distinct regions identified on chromosome 11p. Two regions on 11p13 distal to the Wilms tumor gene WT1 and on 11p15.5 between the markers HBB and D11S860 are described. The third region on the telomere of 11p15.5 has been previously described and is further delineated in this communication. By high-resolution mapping the size of each of these regions was estimated to be 2-3 megabases. The frequency of somatic loss of genetic information in these regions (57%, 71%, and 45%, respectively) was comparable to that seen in heritable tumors such as Wilms tumor (55%) and retinoblastoma (70%) and suggests their involvement in pathogenesis of non-small-cell lung cancer. Gene dosage analyses revealed duplication of the remaining allele in the majority of cases in the 11p13 and the proximal 11p15.5 region but rarely in the distal 11p15.5 region. In tumors with loss of heterozygosity in all three regions any combination of duplication or simple deletion was observed, suggesting that loss of heterozygosity occurs independently and perhaps at different points in time. These results provide a basis for studies directed at cloning potential tumor-suppressor genes in these regions and for assessing their biological and clinical significance in non-small-cell lung cancer. Images PMID:8202519

  12. A genome-wide linkage scan identifies multiple chromosomal regions influencing serum lipid levels in the population on the Samoan islands* s⃞

    PubMed Central

    Åberg, Karolina; Dai, Feng; Sun, Guangyun; Keighley, Ember; Indugula, Subba Rao; Bausserman, Linda; Viali, Satupaitea; Tuitele, John; Deka, Ranjan; Weeks, Daniel E.; McGarvey, Stephen T.

    2008-01-01

    Abnormal lipid levels are important risk factors for cardiovascular diseases. We conducted genome-wide variance component linkage analyses to search for loci influencing total cholesterol (TC), LDL, HDL and triglyceride in families residing in American Samoa and Samoa as well as in a combined sample from the two polities. We adjusted the traits for a number of environmental covariates, such as smoking, alcohol consumption, physical activity, and material lifestyle. We found suggestive univariate linkage with log of the odds (LOD) scores > 3 for LDL on 6p21-p12 (LOD 3.13) in Samoa and on 12q21-q23 (LOD 3.07) in American Samoa. Furthermore, in American Samoa on 12q21, we detected genome-wide linkage (LODeq 3.38) to the bivariate trait TC-LDL. Telomeric of this region, on 12q24, we found suggestive bivariate linkage to TC-HDL (LODeq 3.22) in the combined study sample. In addition, we detected suggestive univariate linkage (LOD 1.9–2.93) on chromosomes 4p-q, 6p, 7q, 9q, 11q, 12q 13q, 15q, 16p, 18q, 19p, 19q and Xq23 and suggestive bivariate linkage (LODeq 2.05–2.62) on chromosomes 6p, 7q, 12p, 12q, and 19p-q. In conclusion, chromosome 6p and 12q may host promising susceptibility loci influencing lipid levels; however, the low degree of overlap between the three study samples strongly encourages further studies of the lipid-related traits. PMID:18594117

  13. Human and mouse chromosomal mapping of the myeloid cell leukemia-1 gene: MCL1 maps to human chromosome 1q21, a region that is frequently altered in preneoplastic and neoplastic disease

    SciTech Connect

    Craig, R.W.; Zhou, P.; Kozopas, K.M.

    1994-09-15

    The MCL1 gene, recently identified in a myeloid leukemia cell line, has sequence similarity to BCL2, the gene at the t(14;18) translocation in follicular lymphoma. The chromosomal location of MCL1 has now been determined. The human locus (MCL1) was mapped to the long arm of human chromosome 1q21, using the methods of in situ hybridization and somatic cell hybrid analysis. In the mouse, MCL1-related sequences were mapped to positions on two mouse chromosomes (chromosomes 3 and 5), using haplotype analysis of an interspecific cross. The location of the locus on mouse chromosome 3 (Mcl1) was homologous to that of MCL1 on human chromosome 1; the second locus (Mcl-rs on mouse chromosome 5) may represent a pseudogene. The proximal long arm of human chromosome 1, where MCL1 is located, is duplicated and/or rearranged in a variety of preneoplastic and neoplastic diseases including hematologic diseases and solid tumors. MCL1 is thus a candidate gene for involvement in cancer. 46 refs., 2 figs., 3 tabs.

  14. Stable Chromosome Condensation Revealed by Chromosome Conformation Capture.

    PubMed

    Eagen, Kyle P; Hartl, Tom A; Kornberg, Roger D

    2015-11-01

    Chemical cross-linking and DNA sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands of polytene chromosomes of Drosophila. We further establish the conservation of TADs between polytene and diploid cells of Drosophila. From direct measurements on light micrographs of polytene chromosomes, we then deduce the states of chromatin folding in the diploid cell nucleus. Two states of folding, fully extended fibers containing regulatory regions and promoters, and fibers condensed up to 10-fold containing coding regions of active genes, constitute the euchromatin of the nuclear interior. Chromatin fibers condensed up to 30-fold, containing coding regions of inactive genes, represent the heterochromatin of the nuclear periphery. A convergence of molecular analysis with direct observation thus reveals the architecture of interphase chromosomes. PMID:26544940

  15. Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis

    SciTech Connect

    Chung, E.; Hanukoglu, A.; Rees, M.; Thompson, R.; Gardiner, R.M.

    1995-10-01

    Pseudohypoaldosteronism type 1 (PHA1) is an uncommon inherited disorder characterized by salt-wasting in infancy arising from target organ unresponsiveness to mineralocorticoids. Clinical expression of the disease varies from severely affected infants who may die to apparently asymptomatic individuals. Inheritance is Mendelian and may be either autosomal dominant or autosomal recessive. A defect in the mineralocortiocoid receptor has been implicated as a likely cause of PHA1. The gene for human mineralocorticoid receptor (MLR) has been cloned and physically mapped to human chromosome 4q31.1-31.2. The etiological role of MLR in autosomal recessive PHA1 was investigated by performing linkage analysis between PHA1 and three simple sequence length polymorphisms (D4S192, D4S1548, and D4S413) on chromosome 4q in 10 consanguineous families. Linkage analysis was carried out assuming autosomal recessive inheritance with full penetrance and zero phenocopy rate using the MLINK program for two-point analysis and the HOMOZ program for multipoint analysis. Lod scores of less than -2 were obtained over the whole region from D4S192 to D4S413 encompassing MLR. This provides evidence against MLR as the site of mutations causing PHA1 in the majority of autosomal recessive families. 34 refs., 3 figs., 2 tabs.

  16. The neurological mouse mutations jittery and hesitant are allelic and map to the region of mouse chromosome 10 homologous to 19p13.3

    SciTech Connect

    Kapfhamer, D.; Sufalko, D.; Warren, S.

    1996-08-01

    Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, uncoordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10 is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic mouse model for human Unverricht-Lundborg progressive myoclonus epilepsy (EPM1) on 21q22.3 nor for spinocerebellar ataxia II (SCA2) on 12q22-q24. The closely linked markers presented here will facilitate positional cloning of the ji gene. 31 refs., 2 figs.

  17. Physical mapping of chromosome 17p13.3 in the region of a putative tumor suppressor gene important in medulloblastoma

    SciTech Connect

    McDonald, J.D.; Daneshvar, L.; Willert, J.R.

    1994-09-01

    Deletion mapping of a medulloblastoma tumor panel revealed loss of distal chromosome 17p13.3 sequences in tumors from 14 of 32 patients (44%). Of the 14 tumors showing loss of heterozygosity by restriction fragment length polymorphism analysis, 14 of 14 (100%) displayed loss of the telomeric marker p144-D6 (D17S34), while a probe for the ABR gene on 17p13.3 was lost in 7 of 8 (88%) informative cases. Using pulsed-field gel electrophoresis, we localized the polymorphic marker (VNTR-A) of the ABR gene locus to within 220 kb of the p144-D6 locus. A cosmid contig constructed in this region was used to demonstrate by fluorescence in situ hybridization that the ABR gene is oriented transcriptionally 5{prime} to 3{prime} toward the telomere. This report provides new physical mapping data for the ABR gene, which has not been previously shown to be deleted in medulloblastoma. These results provide further evidence for the existence of a second tumor suppressor gene distinct from p53 on distal chromosome 17p. 12 refs., 3 figs.

  18. Plasminogen activator inhibitor type 1 gene is located at region q21. 3-q22 of chromosome 7 and genetically linked with cystic fibrosis

    SciTech Connect

    Klinger, K.W.; Winqvist, R.; Riccio, A.; Andreasen, P.A.; Sartorio, R.; Nielsen, L.S.; Stuart, N.; Stanislovitis, P.; Watkins, P.; Douglas, R.

    1987-12-01

    The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with a PAI1 cDNA probe and in situ hybridization, respectively. The authors frequent HindIII restriction fragment length polymorphism (RFLP) of the PAI1 gene with an information content of 0.369. In family studies using this polymorphism, genetic linkage was found between PAI1 and the loci for erythropoietin (EPO), paraoxonase (PON), the met protooncogene (MET), and cystic fibrosis (CF), all previously assigned to the middle part of the long arm of chromosome 7. The linkage with EPO was closest with an estimated genetic distance of 3 centimorgans, whereas that to CF was 20 centimorgans. A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF. The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer.

  19. An isolated case of lissencephaly caused by the insertion of a mitochondrial genome-derived DNA sequence into the 5' untranslated region of the PAFAH1B1 (LIS1) gene.

    PubMed

    Millar, David S; Tysoe, Carolyn; Lazarou, Lazarus P; Pilz, Daniela T; Mohammed, Shehla; Anderson, Katharine; Chuzhanova, Nadia; Cooper, David N; Butler, Rachel

    2010-08-01

    A 130 base pair (bp) insertion (g.-8delCins130) into the 5' untranslated region of the PAFAH1B1 (LIS1) gene, seven nucleotides upstream of the translational initiation site, was detected in an isolated case of lissencephaly. The inserted DNA sequence exhibited perfect homology to two non-contiguous regions of the mitochondrial genome (8479 to 8545 and 8775 to 8835, containing portions of two genes, ATP8 and ATP6 ), as well as near-perfect homology (1 bp mismatch) to a nuclear mitochondrial pseudogene (NUMT) sequence located on chromosome 1p36. This lesion was not evident on polymerase chain reaction (PCR) sequence analysis of either parent, indicating that the mutation had occurred de novo in the patient. Experiments designed to distinguish between a mitochondrial and a nuclear genomic origin for the inserted DNA sequence were, however, inconclusive. Mitochondrial genome sequences from both the patient and his parents were sequenced and found to be identical to the sequence inserted into the PAFAH1B1 gene. Analysis of parental PCR products from the chromosome 1-specific NUMT were also consistent with the interpretation that the inserted sequence had originated directly from the mitochondrial genome. The chromosome 1-specific NUMT in the patient proved to be refractory to PCR analysis, however, suggesting that this region of chromosome 1 could have been deleted or rearranged. Although it remains by far the most likely scenario, in the absence of DNA sequence information from the patient's own chromosome 1-specific NUMT, we cannot unequivocally confirm that the 130 bp insertion originated from mitochondrial genome rather than from the NUMT. PMID:20846927

  20. A testis-specific gene, TPTE, encodes a putative transmembrane tyrosine phosphatase and maps to the pericentromeric region of human chromosomes 21 and 13, and to chromosomes 15, 22, and Y.

    PubMed

    Chen, H; Rossier, C; Morris, M A; Scott, H S; Gos, A; Bairoch, A; Antonarakis, S E

    1999-11-01

    To contribute to the creation of a transcription map of human chromosome 21 (HC21) and to the identification of genes that may be involved in the pathogenesis of Down syndrome, exon trapping was performed from HC21-specific cosmids covering the entire chromosome. More than 700 exons have been identified to date. One such exon, hmc01a06, maps to YAC 831B6 which contains marker D21Z1 (alphoid repeats) and had previously been localized to the pericentromeric region of HC21. Northern-blot analysis revealed a 2.5-kb mRNA species strongly and exclusively expressed in the testis. We cloned the corresponding full-length cDNA, which encodes a predicted polypeptide of 551 amino acids with at least two potential transmembrane domains and a tyrosine phosphatase motif. The cDNA has sequence homology to chicken tensin, bovine auxilin and rat cyclin-G associated kinase (GAK). The entire polypeptide sequence also has significant homology to tumor suppressor PTEN/MMAC1 protein. We termed this novel gene/protein TPTE (transmembrane phosphatase with tensin homology). Polymerase chain reaction amplification, fluorescent in situ hybridization, Southern-blot and sequence analysis using monochromosomal somatic cell hybrids showed that this gene has highly homologous copies on HC13, 15, 22, and Y, in addition to its HC21 copy or copies. The estimated minimum number of copies of the TPTE gene in the haploid human genome is 7 in male and 6 in female. Zoo-blot analysis showed that TPTE is conserved between humans and other species. The biological function of the TPTE gene is presently unknown; however, its expression pattern, sequence homologies, and the presence of a potential tyrosine phosphatase domain suggest that it may be involved in signal transduction pathways of the endocrine or spermatogenetic function of the testis. It is also unknown whether all copies of TPTE are functional or whether some are pseudogenes. TPTE is, to our knowledge, the gene located closest to the human

  1. The Broom of the Sorcerer's Apprentice: The Fine Structure of a Chromosomal Region Causing Reproductive Isolation between Two Sibling Species of Drosophila

    PubMed Central

    Davis, A. W.; Wu, C. I.

    1996-01-01

    How many genes contribute to reproductive isolation between closely related species? We determined the number of genes located in the 9D-12B region of the Drosophila mauritiana X chromosome that cause hybrid male sterility in a D. simulans background. Previous low resolution studies suggested that a single hybrid sterility factor was associated with this region. In this study, by taking advantage of a cluster of visible and DNA markers, we identified three D. mauritiana factors in this region and then subjected one of them to detailed analysis. This factor again turned out to be comprised of three factors; one of which, mapped to within 200 kb, may in fact be two factors. The title refers to this exercise of splitting sterile introgressions into ever smaller ones, each of which retains partial or full sterility effects. In a region representing a mere 3% of the Drosophila genome, no fewer than six loci of hybrid sterility were identified between two sibling species that have not shown clear divergence at the molecular level. These results suggest that levels of genetic divergence between closely related species may be quite high for functionally important traits even when the opposite is true for randomly chosen loci. PMID:8807300

  2. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  3. A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCA1

    PubMed Central

    Godwin, Andrew K.; Vanderveer, Lisa; Schultz, David C.; Lynch, Henry T.; Altomare, Deborah A.; Buetow, Kenneth H.; Daly, Mary; Getts, Lori A.; Masny, Agnes; Rosenblum, Norman; Hogan, Michael; Ozols, Robert F.; Hamilton, Thomas C.

    1994-01-01

    Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17pl3.1 and 17pl3.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17ql2-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans −25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene. ImagesFigure 1Figure 3 PMID:7942844

  4. Genetic and physical mapping of the Treacher Collins syndrome locus with respect to loci in the chromosome 5q3 region

    SciTech Connect

    Jabs, E.W.; Li, Xiang; Coss, C.; Taylor, E. ); Lovett, M. ); Yamaoka, L.H.; Speer, M.C. ); Cadle, R.; Hall, B. ); Brown, K. )

    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.

  5. The chromosome periphery during mitosis.

    PubMed

    Hernandez-Verdun, D; Gautier, T

    1994-03-01

    A complex structure, visible by electron microscopy, surrounds each chromosome during mitosis. The organization of this structure is distinct from that of the chromosomes and the cytoplasm. It forms a perichromosomal layer that can be isolated together with the chromosomes. This layer covers the chromosomes except in centromeric regions. The perichromosomal layer includes nuclear and nucleolar proteins as well as ribonucleoproteins (RNPs). The list of proteins and RNAs identified includes nuclear matrix proteins (perichromin, peripherin), nucleolar proteins (perichro-monucleolin, Ki-67 antigen, B23 protein, fibrillarin, p103, p52), ribosomal proteins (S1) and snRNAs (U3 RNAs). Only limited information is available about how and when the perichromosomal layer is formed. During early prophase, the proteins extend from the nucleoli towards the periphery of the nucleus. Thin cordon-like structures reach the nuclear envelope delimiting areas in which chromosomes condense. At telophase, the proteins are associated with the part of the chromosomes remaining condensed and accumulate in newly formed nucleoli in regions where chromatin is already decondensed. The perichromosomal layer contains several different classes of proteins and RNPs and it has been attributed various roles: (1) in chromosome organization, (2) as a barrier around the chromosomes, (3) involvement in compartmentation of the cells in prophase and telophase and (4) a binding site for chromosomal passenger proteins necessary to the early process of nuclear assembly. PMID:8166671

  6. Refined-mapping of the novel TSG within the 17q24.3 chromosomal region in non-small cell lung cancer samples

    PubMed Central

    Huang, Wayren; Wang, Yiching; Chu, Woeichyn; Tseng, Ruochia

    2016-01-01

    Lung cancer is a leading cause of cancer mortality in Taiwan. It has been previously demonstrated that alterations to tumor suppressor genes (TSGs) are involved in the multi-step carcinogenesis process that results in the development of human cancer, including lung cancer. Both copies of the TSG must be inactivated for their function to be lost. As a result, it is important to search for the genomic regions that potentially contain TSGs and to investigate the etiological association of lung cancer with the allelic deletion of various candidate TSGs. Previous genome-wide loss of heterozygosity (LOH) data has demonstrated that the chromosome region at 17q24.3 was a novel and frequent LOH region that was associated with non-small-cell lung cancer (NSCLC). In the present study, refined mapping using 9 additional microsatellite markers was performed targeting chromosome 17q24.3 by polymerase chain reaction (PCR)-LOH analysis. The allelic loss pattern across 48 available tumors indicates that the minimal deletion region was located between markers D17S1882 and D17S2193 and spanned a distance of approximately 2.7 Mb, reaching 65% LOH at locus D17S1816. A putative gene, LOC51321 (AMZ2), was postulated to be the deletion target on 17q24.3 based on the findings from these NSCLC samples. Reverse transcription-PCR (RT-PCR) expression analysis indicated reduced expression of LOC51321 in 54% (7/13) of the NSCLC cell lines tested and 36% (19/53) of the NSCLC tumor tissue samples analyzed. In CL1-5-F4 cells, low mRNA and protein expression of LOC51321 were associated with the promoter hypermethylation, as determined by RT-PCR, western blotting and methylation-specific PCR assays. In addition, treatment with 5-Aza-deoxycytosine successfully restored mRNA expression by de-methylating the putative promoter region in CL1-5-F4 cells that lacked LOC51321 expression, but did harbor the relevant methylated promoter. These findings indicate that LOC51321 may be involved in lung

  7. Evolution of sex chromosomes ZW of Schistosoma mansoni inferred from chromosome paint and BAC mapping analyses.

    PubMed

    Hirai, Hirohisa; Hirai, Yuriko; LoVerde, Philip T

    2012-12-01

    Chromosomes of schistosome parasites among digenetic flukes have a unique evolution because they exhibit the sex chromosomes ZW, which are not found in the other groups of flukes that are hermaphrodites. We conducted molecular cytogenetic analyses for investigating the sex chromosome evolution using chromosome paint analysis and BAC clones mapping. To carry this out, we developed a technique for making paint probes of genomic DNA from a single scraped chromosome segment using a chromosome microdissection system, and a FISH mapping technique for BAC clones. Paint probes clearly identified each of the 8 pairs of chromosomes by a different fluorochrome color. Combination analysis of chromosome paint analysis with Z/W probes and chromosome mapping with 93 BAC clones revealed that the W chromosome of Schistosoma mansoni has evolved by at least four inversion events and heterochromatinization. Nine of 93 BAC clones hybridized with both the Z and W chromosomes, but the locations were different between Z and W chromosomes. The homologous regions were estimated to have moved from the original Z chromosome to the differentiated W chromosome by three inversions events that occurred before W heterohcromatinization. An inversion that was observed in the heterochromatic region of the W chromosome likely occurred after W heterochromatinization. These inversions and heterochromatinization are hypothesized to be the key factors that promoted the evolution of the W chromosome of S. mansoni. PMID:22831897

  8. Molecular mapping across three populations reveals a QTL hotspot region on chromosome 3 for secondary traits associated with drought tolerance in tropical maize.

    PubMed

    Almeida, Gustavo Dias; Nair, Sudha; Borém, Aluízio; Cairns, Jill; Trachsel, Samuel; Ribaut, Jean-Marcel; Bänziger, Marianne; Prasanna, Boddupalli M; Crossa, Jose; Babu, Raman

    2014-01-01

    Identifying quantitative trait loci (QTL) of sizeable effects that are expressed in diverse genetic backgrounds across contrasting water regimes particularly for secondary traits can significantly complement the conventional drought tolerance breeding efforts. We evaluated three tropical maize biparental populations under water-stressed and well-watered regimes for drought-related morpho-physiological traits, such as anthesis-silking interval (ASI), ears per plant (EPP), stay-green (SG) and plant-to-ear height ratio (PEH). In general, drought stress reduced the genetic variance of grain yield (GY), while that of morpho-physiological traits remained stable or even increased under drought conditions. We detected consistent genomic regions across different genetic backgrounds that could be target regions for marker-assisted introgression for drought tolerance in maize. A total of 203 QTL for ASI, EPP, SG and PEH were identified under both the water regimes. Meta-QTL analysis across the three populations identified six constitutive genomic regions with a minimum of two overlapping traits. Clusters of QTL were observed on chromosomes 1.06, 3.06, 4.09, 5.05, 7.03 and 10.04/06. Interestingly, a ~8-Mb region delimited in 3.06 harboured QTL for most of the morpho-physiological traits considered in the current study. This region contained two important candidate genes viz., zmm16 (MADS-domain transcription factor) and psbs1 (photosystem II unit) that are responsible for reproductive organ development and photosynthate accumulation, respectively. The genomic regions identified in this study partially explained the association of secondary traits with GY. Flanking single nucleotide polymorphism markers reported herein may be useful in marker-assisted introgression of drought tolerance in tropical maize. PMID:25076840

  9. A functional AT/G polymorphism in the 5'-untranslated region of SETDB2 in the IgE locus on human chromosome 13q14.

    PubMed

    Holt, R J; Vandiedonck, C; Willis-Owen, S A; Knight, J C; Cookson, W O; Moffatt, M F; Zhang, Y

    2015-10-01

    The immunoglobulin E (IgE)-associated locus on human chromosome 13q14 influencing asthma-related traits contains the genes PHF11 and SETDB2. SETDB2 is located in the same linkage disequilibrium region as PHF11 and polymorphisms within SETDB2 have been shown to associate with total serum IgE levels. In this report, we sequenced the 15 exons of SETDB2 and identified a single previously ungenotyped mutation (AT/G, rs386770867) in the 5'-untranslated region of the gene. The polymorphism was found to be significantly associated with serum IgE levels in our asthma cohort (P=0.0012). Electrophoretic mobility shift assays revealed that the transcription factor Ying Yang 1 binds to the AT allele, whereas SRY (Sex determining Region Y) binds to the G allele. Allele-specific transcription analysis (allelotyping) was performed in 35 individuals heterozygous for rs386770867 from a panel of 200 British families ascertained through probands with severe stage 3 asthma. The AT allele was found to be significantly overexpressed in these individuals (P=1.26×10(-21)). A dual-luciferase assay with the pGL3 luciferase reporter gene showed that the AT allele significantly affects transcriptional activities. Our results indicate that the IgE-associated AT/G polymorphism (rs386770867) regulates transcription of SETDB2. PMID:26378653

  10. Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13

    SciTech Connect

    Gong, Yaoqin; Liu, Jin; Warman, M.L.

    1996-07-01

    Osteoporosis-pseudoglioma syndrome (OPS) is an autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or juvenile-onset blindness. The pathogenic mechanism is not known. Clinical, biochemical, and microscopic analyses suggest that OPS may be a disorder of matrix homeostasis rather than a disorder of matrix structure. Consequently, identification of the OPS gene and its protein product could provide insights regarding common osteoporotic conditions, such as postmenopausal and senile osteoporosis. As a first step toward determining the cause of OPS, we utilized a combination of traditional linkage analysis and homozygosity mapping to assign the OPS locus to chromosome region 11q12-13. Mapping was accomplished by analyzing 16 DNA samples (seven affected individuals) from three different consanguineous kindreds. Studies in 10 additional families narrowed the candidate region, supported locus homogeneity, and did not detect founder effects. The OPS locus maps to a 13-cM interval between D11S1298 and D11S971 and most likely lies in a 3-cM region between GSTP1 and D11S1296. At present, no strong candidate genes colocalize with OPS. 33 refs., 2 figs., 1 tab.

  11. A functional AT/G polymorphism in the 5′-untranslated region of SETDB2 in the IgE locus on human chromosome 13q14

    PubMed Central

    Holt, R J; Vandiedonck, C; Willis-Owen, S A; Knight, J C; Cookson, W O; Moffatt, M F; Zhang, Y

    2015-01-01

    The immunoglobulin E (IgE)-associated locus on human chromosome 13q14 influencing asthma-related traits contains the genes PHF11 and SETDB2. SETDB2 is located in the same linkage disequilibrium region as PHF11 and polymorphisms within SETDB2 have been shown to associate with total serum IgE levels. In this report, we sequenced the 15 exons of SETDB2 and identified a single previously ungenotyped mutation (AT/G, rs386770867) in the 5′-untranslated region of the gene. The polymorphism was found to be significantly associated with serum IgE levels in our asthma cohort (P=0.0012). Electrophoretic mobility shift assays revealed that the transcription factor Ying Yang 1 binds to the AT allele, whereas SRY (Sex determining Region Y) binds to the G allele. Allele-specific transcription analysis (allelotyping) was performed in 35 individuals heterozygous for rs386770867 from a panel of 200 British families ascertained through probands with severe stage 3 asthma. The AT allele was found to be significantly overexpressed in these individuals (P=1.26 × 10−21). A dual-luciferase assay with the pGL3 luciferase reporter gene showed that the AT allele significantly affects transcriptional activities. Our results indicate that the IgE-associated AT/G polymorphism (rs386770867) regulates transcription of SETDB2. PMID:26378653

  12. Structure and function of eukaryotic chromosomes

    SciTech Connect

    Hennig, W.

    1987-01-01

    Contents: Introduction; Polytene Chromosomel Giant Chromosomes in Ciliates; The sp-I Genes in the Balbiani Rings of Chironomus Salivary Glands; The White Locus of Drosophila Melanogaster; The Genetic and Molecular Organization of the Dense Cluster of Functionally Related Vital Genes in the DOPA Decarboxylase Region of the Drosophila melanogaster Genome; Heat Shock Puffs and Response to Environmental Stress; The Y Chromosomal Lampbrush Loops of Drosophila; Contributions of Electron Microscopic Spreading Preparations (''Miller Spreads'') to the Analysis of Chromosome Structure; Replication of DNA in Eukaryotic Chromosomes; Gene Amplification in Dipteran Chromosomes; The Significance of Plant Transposable Elements in Biologically Relevant Processes; Arrangement of Chromosomes in Interphase Cell Nuclei; Heterochromatin and the Phenomenon of Chromosome Banding; Multiple Nonhistone Protein-DNA Complexes in Chromatin Regulate the Cell- and Stage-Specific Activity of an Eukaryotic Gene; Genetics of Sex Determination in Eukaryotes; Application of Basic Chromosome Research in Biotechnology and Medicine. This book presents an overview of various aspects of chromosome research.

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

    PubMed Central

    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 this study was to elucidate the involvement of deregulations within the Dlk1-Dio3 region in GCT pathogenesis. Methods Quantitative gene and microRNA expression analyses were performed on GCTSCs and MSCs with or without treatment with epigenetic modifiers. Methylation analysis of differentially methylated regions was performed by bisulfite sequencing. Results In addition to microRNA silencing we detected a significant downregulation of Dlk1, Meg3 and Meg8 in GCTSCs compared to MSCs. DNA methylation analyses of the Meg3-DMR and IG-DMR revealed a frequent hypermethylation within the IG-DMR in GCTs. Epigenetic modification could restore expression of some but not all analyzed genes and microRNAs suggesting further regulatory mechanisms. Conclusion Epigenetic silencing of genes and microRNAs within the Dlk1-Dio3 region is a common event in GCTSCs, in part mediated by hypermethylation within the IG-DMR. The identified genes, micro RNAs and microRNA target genes might be valuable targets for the development of improved strategies for GCT diagnosis and therapy. PMID:25005035

  14. The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD)

    PubMed Central

    Pointon, Jennifer J; Harvey, David; Karaderi, Tugce; Appleton, Louise H; Farrar, Claire; Stone, Millicent A; Sturrock, Roger D; Reveille, John D; Weisman, Michael H; Ward, Michael M; Brown, Matthew A; Wordsworth, B Paul

    2010-01-01

    Objective To replicate and refine the reported association of ankylosing spondylitis (AS) with two non-synonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. Methods Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. Results The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. Conclusions The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS. PMID:19854717

  15. The gene for human erythrocyte membrane protein band 7. 2 (EPB72) maps to 9q33-q34 centromeric to the Philadelphia chromosome translocation breakpoint region

    SciTech Connect

    Gallagher, P.G.; Upender, M.; Ward, D.C.; Forget, B.G. )

    1993-10-01

    Erthrocyte band 7.2b is a 31-kDa integral phosphoprotein absent from the erythrocytes of many patients with hereditary stomatocytosis (HSt). HSt is a heterogeneous group of disorders characterized by mouth-shaped erythrocyte morphology on peripheral blood smears. The clinical severity of HSt is variable; some patients experience hemolysis and anemia while others are asymptomatic. The red cell membranes of these patients usually exhibit abnormal permeability to sodium and potassium with resultant modification of intracellular water content. The band 7.2b protein has been purified and the cDNA cloned. The approved gene name and symbol are erythrocyte membrane protein band 7.2 and EPB72, respectively, as assigned by the Human Gene Nomenclature Committee. Using a human reticulocyte cDNA library as template, a 491-bp fragment corresponding to the 3' end of the coding region of the EPB72 cDNA was amplified. Three overlapping phase DNA clones were isolated using this probe. Four genomic DNA fragments of 2.0, 2.5, 4.5, and 5.0 kb, respectively, were isolated from these clones. To localize the EPB72 gene by fluorescence in situ hybridization, these genomic DNA fragments were labeled with biotin-11-dUTP and hybridized to metaphase chromosomes as described. Probes were preannealed to C[sub 0]t1-fractionated DNA to block repetitive sequences. Experiments were analyzed and digitally imaged using a cooled CCD camera. The probes, in combination, gave specific hybridization signals only in chromosome 9q. The gene for erythrocyte membrane protein 7.2 localized to 9q33-q34.

  16. Deletion Mapping of Four Loci Defined by N-Ethyl-N-Nitrosourea-Induced Postimplantation-Lethal Mutations within the Pid-Hbb Region of Mouse Chromosome 7

    PubMed Central

    Rinchik, E. M.; Carpenter, D. A.; Long, C. L.

    1993-01-01

    As part of a long-term effort to refine the physical and functional maps of the Fes-Hbb region of mouse chromosome 7, four loci [l(7)1Rn, l(7)2Rn, l(7)3Rn, l(7)4Rn] defined by N-ethyl-N-nitrosourea (ENU)-induced, prenatally lethal mutations were mapped by means of trans complementation crosses to mice carrying lethal deletions of the mouse chromosome-7 albino (c) locus. Each locus was assigned to a defined subregion of the deletion map at the distal end of the Fes-Hbb interval. Of particular use for this mapping were preimplantation-lethal deletions having distal breakpoints localized between pid and Omp. Hemizygosity or homozygosity for each of the ENU-induced lethals was found to arrest development after uterine implantation; the specific time of postimplantation death varied, and depended on both the mutation itself and on whether it was hemizygous or homozygous. Based on their map positions outside of and distal to deletions that cause death at preimplantation stages, these ENU-induced mutations identify loci, necessary for postimplantation development, that could not have been discovered by phenotypic analyses of mice homozygous for any albino deletion. The mapping of these loci to specific genetic intervals defined by deletion breakpoints suggests a number of positional-cloning strategies for the molecular isolation of these genes. Phenotypic and genetic analyses of these mutations should provide useful information on the functional composition of the corresponding segment of the human genome (perhaps human 11q13.5). PMID:8307327

  17. Comparability of multiple data types from the Bering Strait region: cranial and dental metrics and nonmetrics, mtDNA, and Y-chromosome DNA.

    PubMed

    Herrera, Brianne; Hanihara, Tsunehiko; Godde, Kanya

    2014-07-01

    Different data types have previously been shown to have the same microevolutionary patterns in worldwide data sets. However, peopling of the New World studies have shown a difference in migration paths and timings using multiple types of data, spurring research to understand why this is the case. This study was designed to test the degree of similarity in evolutionary patterns by using cranial and dental metric and nonmetric data, along with Y-chromosome DNA and mtDNA. The populations used included Inuits from Alaska, Canada, Siberia, Greenland, and the Aleutian Islands. For comparability, the populations used for the cranial and molecular data were from similar geographic regions or had a shared population history. Distance, R and kinship matrices were generated for use in running Mantel tests, PROTEST analyses, and Procrustes analyses. A clear patterning was seen, with the craniometric data being most highly correlated to the mtDNA data and the cranial nonmetric data being most highly correlated with the Y-chromosome data, while the phenotypic data were also linked. This patterning is suggestive of a possible male or female inheritance, or the correlated data types are affected by the same or similar evolutionary forces. The results of this study indicate cranial traits have some degree of heritability. Moreover, combining data types leads to a richer knowledge of biological affinity. This understanding is important for bioarchaeological contexts, in particular, peopling of the New World studies where focusing on reconciling the results from comparing multiple data types is necessary to move forward. PMID:24643445

  18. Characterization of an Autism-Associated Segmental Maternal Heterodisomy of the Chromosome 15q11-13 Region

    ERIC Educational Resources Information Center

    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…

  19. A region of barley chromosome 6H harbors multiple major genes associated with net type blotch resistance.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Net type of net blotch (NTNB) on barley, caused by Pyrenophora teres f. teres Drechs. is prevalent in barley growing regions worldwide and is particularly damaging under cool, wet conditions. A population of 118 doubled haploid (DH) lines developed from a cross between barley cultivars ‘Rika’ and ‘K...

  20. Identification of genetic and environmental factors stimulating excision from Streptomyces scabiei chromosome of the toxicogenic region responsible for pathogenicity.

    PubMed

    Chapleau, Mélanie; Guertin, Julien F; Farrokhi, Ali; Lerat, Sylvain; Burrus, Vincent; Beaulieu, Carole

    2016-05-01

    The genes conferring pathogenicity in Streptomyces turgidiscabies, a pathogen causing common scab of potato, are grouped together on a pathogenicity island (PAI), which has been found to be mobile and appears to transfer and disseminate like an integrative and conjugative element (ICE). However, in Streptomyces scabiei, another common scab-inducing species, the pathogenicity genes are clustered in two regions: the toxicogenic region (TR) and the colonization region. The S. scabiei 87.22 genome was analysed to investigate the potential mobility of the TR. Attachment sites (att), short homologous sequences that delineate ICEs, were identified at both extremities of the TR. An internal att site was also found, suggesting that the TR has a composite structure (TR1 and TR2). Thaxtomin biosynthetic genes, essential for pathogenicity, were found in TR1, whereas candidate genes with known functions in recombination, replication and conjugal transfer were found in TR2. Excision of the TR1 or TR2 subregions alone, or of the entire TR region, was observed, although the excision frequency of TR was low. However, the excision frequency was considerably increased in the presence of either mitomycin C or Streptomyces coelicolor cells. A composite TR structure was not observed in all S. scabiei and Streptomyces acidiscabies strains tested. Of the ten strains analysed, seven lacked TR2 and no TR excision event could be detected in these strains, thus suggesting the implication of TR2 in the mobilization of S. scabiei TR. PMID:26177341

  1. A large duplicated area in the polycystic kidney disease 1 (PKD1) region of chromosome 16 is prone to rearrangement

    SciTech Connect

    Harris, P.C.; Thomas, S.; MacCarthy, A.B.

    1994-09-15

    An area of 500 kb at the proximal end of the polycystic kidney disease 1 (PKD1) region has been mapped in detail, with 260 kb cloned in cosmids. The area cloned from normal individuals contains two homologus but divergent regions each of 75 kb, including the previously described marker 26-6. Pulsed-field gel electrophoresis identified a duplication of 75 kb of this region, referred to as the OX duplication (OXdup), in three patients with PKD1. The OXdup probably arose by an unequal exchange promoted by misalignment of partially homologous areas. Study of the OXdup in a large PKD1 in just one-half of the family, indicating that a recent crossover had occurred between the OXdup and PKD1 and showing that it was not a PKD1 mutation. Further analysis identified an OXdup breakpoint fragment: the OXdup was subsequently identified in 2 normal individuals of 110 assayed. The finding of the OXdup and in other individuals an 11-kb deletion (OXdel) at a similar point within this duplicated area indicates that this is an unusually unstable genomic region. 41 refs., 6 figs.

  2. Synthetic chromosomes.

    PubMed

    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. PMID:26111960

  3. Chromosome and cell genetics

    SciTech Connect

    Sharma, A.K.; Sharma, A.

    1985-01-01

    This book contains 11 chapters. Some of the titles are: Chromosomes in differentiation; Chromosome axis; Nuclear and organelle split genes; Chemical mutagenesis; and Chromosome architecture and additional elements.

  4. Human endopeptidase (THOP1) is localized on chromosome 19 within the linkage region for the late-onset Alzheimer disease AD2 locus

    SciTech Connect

    Meckelein, B.; Abraham, C.R.; De Silva, H.A.R.

    1996-01-15

    A cDNA encoding the rat endopeptidase 24.15 was used to determine the chromosomal localization of the respective human gene. Hybridization to DNA from human-rodent somatic cell hybrids assigned the human gene to chromosome 19. Fluorescence in situ hybridization on human metaphase chromosomes localized the human endopeptidase 24.15 to 19q13.3. 27 refs., 1 fig., 1 tab.

  5. Methods for chromosome-specific staining

    DOEpatents

    Gray, J.W.; Pinkel, D.

    1995-09-05

    Methods and compositions for chromosome-specific staining are provided. Compositions comprise heterogeneous mixtures of labeled nucleic acid fragments having substantially complementary base sequences to unique sequence regions of the chromosomal DNA for which their associated staining reagent is specific. Methods include ways for making the chromosome-specific staining compositions of the invention, and methods for applying the staining compositions to chromosomes. 3 figs.

  6. Mapping of BnMs4 and BnRf to a common microsyntenic region of Arabidopsis thaliana chromosome 3 using intron polymorphism markers.

    PubMed

    Xia, Shengqian; Cheng, Ling; Zu, Feng; Dun, Xiaoling; Zhou, Zhengfu; Yi, Bin; Wen, Jing; Ma, Chaozhi; Shen, Jinxiong; Tu, Jinxing; Fu, Tingdong

    2012-05-01

    A recessive epistatic genic male sterile two-type line, 7365AB (Bnms3ms3ms4msRrfRf/BnMs3ms3ms4ms4RfRf), combined with the fertile interim-maintainer 7365C (Bnms3ms3ms4ms4rfrf) is an effective pollination control system in hybrid rapeseed production. We report an effective strategy used to fine map BnMs4 and BnRf. The two genes were both defined to a common microsyntenic region with Arabidopsis chromosome 3 using intron polymorphism (IP) markers developed according to Arabidopsis genome information and published genome organization of the A genome. The near-isogenic lines 7365AC (Bnms3ms3ms4ms4Rfrf/Bnms3ms3ms4ms4rfrf) of BnRf and 736512AB (Bnms3ms3Ms4ms4RfRf/Bnms3ms3ms4ms4RfRf) of BnMs4 were constructed to screen developed markers and create genetic linkage maps. Nine polymorphic IP markers (P1-P9) were identified. Of these, P2, P3, P4, and P6 were linked to both BnMs4 and BnRf with genetic distances <0.6 cM. Three simple sequence repeat markers, SR2, SR3, and SR5, were also identified by using public information. Subsequently, all markers linked to the two genes were used to compare the micro-collinearity of the regions flanking the two genes with Brassica rapa and Arabidopsis. The flanking regions showed rearrangements and inversion with fragments of different Arabidopsis chromosomes, but a high collinearity with B. rapa. This collinearity provided extremely valuable reference for map-based cloning in polyploid Brassica species. These IP markers could be exploited for comparative genomic studies within and between Brassica species, providing an economically feasible approach for molecular marker-assisted selection breeding, accelerating the process of gene cloning, and providing more direct evidence for the presence of multiple alleles between BnMs4 and BnRf. PMID:22246313

  7. Evaluation of polymorphisms within the genes GSHR and SLC2A2 that are within a region on bovine chromosome 1 (BTA1) previously associated with feed intake and weight gain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cost of feed is the largest expense incurred by cattle producers. The ability to select for animals with beneficial production traits using genetic markers may reduce expenses for producers. A large region on bovine chromosome 1 was identified as significant for average daily feed intake (ADFI) and ...

  8. Distinct deleted regions on chromosome segment 16q23-24 associated with metastases in prostate cancer.

    PubMed

    Li, C; Berx, G; Larsson, C; Auer, G; Aspenblad, U; Pan, Y; Sundelin, B; Ekman, P; Nordenskjöld, M; van Roy, F; Bergerheim, U S

    1999-03-01

    Cadherins (CDH) are cell adhesion molecules and their dysfunctions have been implicated in the development of cancer metastases. Several cadherin genes are tandemly located on 16q, which is frequently deleted in prostate cancer. We therefore used 22 markers on 16q to localize important deleted regions in metastases of this tumor. We found 16q deletions in 24/32 (75%) tumors. All lymph node and brain metastases showed extensive deletions, while 52% of primary tumors displayed limited deletions. Commonly deleted regions (CDRs) on 16q23-24, CDR2 (D16S515-D16S516) and CDR4 (D16S520-D13S3028), were strongly associated with metastases and increased Gleason score. Reduced CDH1 (E-cadherin) expression was seen in 16/32 (50%) tumors, but the CDH1 gene is not within either of these two regions. Sequencing analysis for all 16 exons of the CDH1 gene did not reveal any mutations in 10 tumors, including three brain metastases with both 16q22.1 deletion and absent E-cadherin expression. Our results implicate other, yet unidentified genes on 16q23-24 to be the frequent targets of mutations and deletions in prostate cancer metastases. PMID:10451696

  9. Investigating the prehistory of Tungusic peoples of Siberia and the Amur-Ussuri region with complete mtDNA genome sequences and Y-chromosomal markers.

    PubMed

    Duggan, Ana T; Whitten, Mark; Wiebe, Victor; Crawford, Michael; Butthof, Anne; Spitsyn, Victor; Makarov, Sergey; Novgorodov, Innokentiy; Osakovsky, Vladimir; Pakendorf, Brigitte

    2013-01-01

    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. PMID:24349531

  10. Genetic map of the region around grizzled (gr) and mocha (mh) on mouse chromosome 10, homologous to human 19p13.3

    SciTech Connect

    Kapfhamer, D.; Burmeister, M.

    1994-10-01

    Grizzled (gr) is a recessive mouse mutation resulting in a gray coat color and reduced perinatal viability. Mocha (mh) is one of several recessive mouse mutants characterized by platelet storage pool disorder, pigment abnormalities, reduced fertility, kidney function deficiencies, and, in some mutants, inner ear and natural killer cell deficiencies. Murine platelet storage pool deficient mutants may be models for Chediak-Higashi and Hermansky-Pudlak syndromes in humans. The genes for gr and mh are very closely linked to each other (0 {+-} 1.2 cM). However, their relative position with respect to molecular markers was previously unknown. Thus, genetic mapping of the gr locus will also yield information about the mh location. To map these two genes genetically, we have performed an intersubspecific backcross of grizzled mice with Mus musculus castaneus. In 539 progeny tested, we found no recombination between the gr gene, the gene for anti-Muellerian hormone (Amh), and the microsatellite markers D10Mit7, D10Mit21, and D10Mit23. One recombination event for each of the flanking markers Basigin (Bsg) and D10Mit22 was identified. These closely linked markers should provide entry points for positional cloning of the gr and mh genes. The region linked to grizzled is homologous to a gene-rich region on human Chromosome 19p13.3.

  11. Genetic map of the region around grizzled (gr) and mocha (mh) on mouse chromosome 10, homologous to human 19p13.3.

    PubMed

    Kapfhamer, D; Burmeister, M

    1994-10-01

    Grizzled (gr) is a recessive mouse mutation resulting in a gray coat color and reduced perinatal viability. Mocha (mh) is one of several recessive mouse mutants characterized by platelet storage pool disorder, pigment abnormalities, reduced fertility, kidney function deficiencies, and, in some mutants, inner ear and natural killer cell deficiencies. Murine platelet storage pool deficient mutants may be models for Chediak-Higashi and Hermansky-Pudlak syndromes in humans. The genes for gr and mh are very closely linked to each other (0 +/- 1.2 cM). However, their relative position with respect to molecular markers was previously unknown. Thus, genetic mapping of the gr locus will also yield information about the mh location. To map these two genes genetically, we have performed an intersubspecific backcross of grizzled mice with Mus musculus castaneus. In 539 progeny tested, we found no recombination between the gr gene, the gene for anti-Muellerian hormone (Amh), and the microsatellite markers D10Mit7, D10Mit21, and D10Mit23. One recombination event for each of the flanking markers Basigin (Bsg) and D10Mit22 was identified. These closely linked markers should provide entry points for positional cloning of the gr and mh genes. The region linked to grizzled is homologous to a gene-rich region on human Chromosome 19p13.3. PMID:7851892

  12. Investigating the Prehistory of Tungusic Peoples of Siberia and the Amur-Ussuri Region with Complete mtDNA Genome Sequences and Y-chromosomal Markers

    PubMed Central

    Duggan, Ana T.; Whitten, Mark; Wiebe, Victor; Crawford, Michael; Butthof, Anne; Spitsyn, Victor; Makarov, Sergey; Novgorodov, Innokentiy; Osakovsky, Vladimir; Pakendorf, Brigitte

    2013-01-01

    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. PMID:24349531

  13. Genomic structure and precise mapping of a thymic regulatory region on mouse chromosome 17 revealed by a c-myc transgene insertion

    SciTech Connect

    Lavenu, A.; Morello, D.; Roland, J.

    1996-06-15

    In one transgenic strain harboring a human c-myc proto-oncogene construct, the transgene was actively and exclusively expressed in the thymus, where it contributed to the development of lymphoma that corresponded to CD4{sup +}CD8{sup +} cells. Here, we have pursued the analysis of transgene expression in healthy transgenic mice and show that transgene activation occurs in the thymus 3 days before birth, at a time when CD4{sup +}CD8{sup +} lymphocytes emerge. In the adult, its expression is restricted to the CD4{sup +}CD8{sup +} cells. The region flanking the transgene insertion site was isolated and made it possible to map the preintegration locus, hereafter called Tsil (for thymus-specific integration locus) on chromosome 17 between D17Rp11e and Ras12-3. A YAC that contains both Tsil and the Pim2 locus, previously shown to be involved in progression of T-cell lymphoma, was isolated. Analysis of Tsil offers a unique opportunity to identify a regulatory region or a gene that might play an important role in T-cell maturation. 41 refs., 5 figs., 2 tabs.

  14. Refining the region of branchio-oto-renal syndrome and defining the flanking markers on chromosome 8q by genetic mapping

    SciTech Connect

    Kumar, S.; Kimberling, W.J.; Connolly, C.J.; Tinley, S.; Marres, H.A.M.; Cremers, C.W.R.J.

    1994-12-01

    Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder associated with external-, middle-, and inner-ear malformations, branchial cleft sinuses, cervical fistulas, mixed hearing loss, and renal anomalies. The gene for BOR was mapped to the long arm of chromosome 8q. Several polymorphic dinucleotide repeat markers were investigated for linkage in two large BOR families, and the region of localization was refined. Two-point linkage analysis yielded the maximum lod scores of 7.44 at {theta} = .03 and 6.71 at {theta} = .04, with markers D8S279 and D8S260, respectively. A multipoint analysis was carried out to position the BOR gene with a defined region using markers D8S165, D8S285, PENK, D8S166, D8S260, D8S279, D8S164, D8S286, D8S84, D8S275, D8S167, D8S273, and D8S271. Haplotype analysis of recombination events at these polymorphic loci was also performed in multigeneration BOR kindreds. The linkage analysis and analysis of recombination events identified markers that clearly flank the BOR locus. The order was determined to be D8S260-BOR-D8S279 at odds > 10{sup 3}:1 over the other possible orders. This flanking markers provide a resource for high-resolution mapping toward cloning and characterizing the BOR gene.

  15. Functional analysis of genes implicated in Down syndrome: 2. Laterality and corpus callosum size in mice transpolygenic for Down syndrome chromosomal region -1 (DCR-1).

    PubMed

    Roubertoux, Pierre L; Bichler, Zoë; Pinoteau, Walter; Seregaza, Zohra; Fortes, Sylvia; Jamon, Marc; Smith, Desmond J; Rubin, Edward; Migliore-Samour, Danièle; Carlier, Michèle

    2005-05-01

    The association between atypical laterality and mental retardation has been reported several times, particularly in Down syndrome (DS). We investigated common genetic correlates of these components of the syndrome, examining direction (number of right paw entries in the Collins test) and degree (absolute difference between the number of right paw entries and the number of left paw entries) in mice that had incorporated extra-contiguous HSA21 fragments covering DCR-1 (Down Chromosomal Region-1). As corpus callosum size is substantially reduced in DS, and as the structure has been suspected of playing a role in atypical laterality, we also measured the corpus callosum in these mice. Extra copies of two regions (F7 and E6) have been associated with an atypical degree of laterality (strongly reduced degree). Extra copies of E8, G6 and E6 are also linked to the reduced size of the corpus callosum, indicating that the abnormal number of fibers linking the two hemispheres is not associated with atypical laterality in DS. Together, these results indicate that some of the genes involved in atypical laterality and in the reduced size of the corpus callosum in DS are present on DCR-1. An extra copy of F7 and, to a lesser extent, an extra copy of E6, are also associated with cognitive impairment. These results support the hypothesis of common genetic correlates in atypical laterality and mental retardation in DS. PMID:15864448

  16. A widely expressed transcription factor with multiple DNA sequence specificity, CTCF, is localized at chromosome segment 16q22.1 within one of the smallest regions of overlap for common deletions in breast and prostate cancers.

    PubMed

    Filippova, G N; Lindblom, A; Meincke, L J; Klenova, E M; Neiman, P E; Collins, S J; Doggett, N A; Lobanenkov, V V

    1998-05-01

    The cellular protooncogene MYC encodes a nuclear transcription factor that is involved in regulating important cellular functions, including cell cycle progression, differentiation, and apoptosis. Dysregulated MYC expression appears critical to the development of various types of malignancies, and thus factors involved in regulating MYC expression may also play a key role in the pathogenesis of certain cancers. We have cloned one such MYC regulatory factor, termed CTCF, which is a highly evolutionarily conserved-11-zinc finger transcriptional factor possessing multiple DNA sequence specificity. CTCF binds to a number of important regulatory regions within the 5' noncoding sequence of the human MYC oncogene, and it can regulate its transcription in several experimental systems. CTCF mRNA is expressed in cells of multiple different lineages. Enforced ectopic expression of CTCF inhibits cell growth in culture. Southern blot analyses and fluorescence in situ hybridization (FISH) with normal human metaphase chromosomes showed that the human CTCF is a single-copy gene situated at chromosome locus 16q22. Cytogenetic studies have pointed out that chromosome abnormalities (deletions) at this locus frequently occur in many different human malignancies, suggesting the presence of one or more tumor suppressor genes in the region. To narrow down their localization, several loss of heterozygosity (LOH) studies of chromosome arm 16q in sporadic breast and prostate cancers have been carried out to define the most recurrent and smallest region(s) of overlap (SRO) for commonly deleted chromosome arm 16q material. For CTCF to be considered as a candidate tumor suppressor gene associated with tumorigenesis, it should localize within one of the SROs at 16q. Fine-mapping of CTCF has enabled us to assign the CTCF gene to about a 2 centiMorgan (cM) interval of 16q22.1 between the somatic cell hybrid breakpoints CY130(D) and CY4, which is between markers D16S186 (16AC16-101) and D16S496

  17. Two-dimensional electrophoretic mobility shift assay: identification and mapping of transcription factor CTCF target sequences within an FXYD5-COX7A1 region of human chromosome 19.

    PubMed

    Vetchinova, Anna S; Akopov, Sergey B; Chernov, Igor P; Nikolaev, Lev G; Sverdlov, Eugene D

    2006-07-01

    An approach for fast identification and mapping of transcription factor binding sites within long genomic sequences is proposed. Using this approach, 10 CCCTC-binding factor (CTCF) binding sites were identified within a 1-Mb FXYD5-COX7A1 human chromosome 19 region. In vivo binding of CTCF to these sites was verified by chromatin immunoprecipitation assay. CTCF binding sites were mapped within gene introns and intergenic regions, and some of them contained Alu-like repeated elements. PMID:16701069

  18. Localization of cDNAs to a region poorly represented in the CEPH chromosome 21 YAC contig: Candidate genes for genetic diseases mapped to 21q22.3

    SciTech Connect

    Gardiner, K.; Patterson, D.; Ichikawa, H.; Ohki, Misao; Cheng, Jan-Fang

    1995-11-20

    Fifty-three cDNA fragments previously obtained by hybridization selection from random clones in the chromosome 21 cosmid library LL21CNO2 failed to identify clones in the chromosome 21 YAC contig described. Using an expanded panel of somatic cell hybrids, we have verified that the majority of these cDNAs map to chromosome 21 and that in particular a very high proportion, {approximately}85%, localize to a 5-Mb region of distal 21q22.3. Pulsed-field analysis coupled with information from the NotI restriction map of the region further indicate that 17 cDNA fragments map within 650 kb of the PFKL gene and thus may be candidates for genetic diseases linked to this gene. This work helps to characterize a region poorly represented in the CEPH YAC contig and adds to the number of cDNAs useful in analysis of chromosome 21-associated diseases. 4 refs., 3 figs., 1 tab.

  19. Organization of the R chromosome region in maize: Final progress report, June 1, 1983--May 31, 1986

    SciTech Connect

    Kermicle, J.

    1989-02-01

    For the present study, insertional mutagenesis using transposable sequences proved the most effective means of producing /und R/ variants for fine structure study. Considerable effort was directed toward developing this means of mutagenesis. It was also necessary to describe the pattern of recombination that prevailed in this region when insertions were present. Thus some of the topics considered as separate items in the following discussion concern transposable element behavior and recombination as such. Until recently, genetic analysis had been the principal means of investigating /und R/ structure and function. With the advent of molecular cloning of maize genes by transposon tagging, a more direct means of investigating /und R/ structure was envisioned. This possibility was realized. We are now collaborating with these investigators to integrate genetic and molecular sources of evidence. This document summarizes publications of research sponsored by this grant, and recent findings that appear to be major advances but concerning which further experiments are in progress. 12 refs.

  20. Identifying chromosomal selection-sweep regions in facial eczema selection-line animals using an ovine 50K-SNP array.

    PubMed

    Phua, S H; Brauning, R; Baird, H J; Dodds, K G

    2014-04-01

    Facial eczema (FE) is a hepato-mycotoxicosis found mainly in New Zealand sheep and cattle. When genetics was found to be a factor in FE susceptibility, resistant and susceptible selection lines of Romney sheep were established to enable further investigations of this disease trait. Using the Illumina OvineSNP50 BeadChip, we conducted a selection-sweep experiment on these FE genetic lines. Two analytical methods were used to detect selection signals, namely the Peddrift test (Dodds & McEwan, 1997) and fixation index FST (Weir & Hill, 2002). Of 50 975 single nucleotide polymorphism (SNP) markers tested, there were three that showed highly significant allele frequency differences between the resistant and susceptible animals (Peddrift nominal P < 0.000001). These SNP loci are located on chromosomes OAR1, OAR11 and OAR12 that coincide precisely with the three highest genomic FST peaks. In addition, there are nine less significant Peddrift SNPs (nominal P ≤ 0.000009) on OAR6 (n = 2), OAR9 (n = 2), OAR12, OAR19 (n = 2), OAR24 and OAR26. In smoothed FST (five-SNP moving average) plots, the five most prominent peaks are on OAR1, OAR6, OAR7, OAR13 and OAR19. Although these smoothed FST peaks do not coincide with the three most significant Peddrift SNP loci, two (on OAR6 and OAR19) overlap with the set of less significant Peddrift SNPs above. Of these 12 Peddrift SNPs and five smoothed FST regions, none is close to the FE candidate genes catalase and ABCG2; however, two on OAR1 and one on OAR13 fall within suggestive quantitative trait locus regions identified in a previous genome screen experiment. The present studies indicated that there are at least eight genomic regions that underwent a selection sweep in the FE lines. PMID:24521158

  1. Adipose and Muscle Tissue Gene Expression of Two Genes (NCAPG and LCORL) Located in a Chromosomal Region Associated with Cattle Feed Intake and Gain

    PubMed Central

    Lindholm-Perry, Amanda K.; Kuehn, Larry A.; Oliver, William T.; Sexten, Andrea K.; Miles, Jeremy R.; Rempel, Lea A.; Cushman, Robert A.; Freetly, Harvey C.

    2013-01-01

    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. PMID:24278337

  2. Genetic mapping of Cmv1 in the region of mouse chromosome 6 encoding the NK gene complex-associated loci Ly49 and musNKR-P1

    SciTech Connect

    Scalzo, A.A.; Lyons, P.A.; Fitzgerald, N.A.

    1995-06-10

    The Cmv1 resistance gene controls splenic replication of murine cytomegalovirus (MCMV) and confers natural killer (NK) cell-mediated resistance to otherwise lethal infection. The Cmv1 phenotypes of 13 inbred mouse strains have been assessed, and it was found that the Cmv1{sup r} resistance phenotype was restricted to the C57BL/6J and Ma/MyJ strains. We have further analyzed the linkage of Cmv1 to the NK gene complex (NKC) mapping to distal mouse chromosome 6 in 99 (BALB/c x C57BL/6J)F{sub 1} x BALB/c backcross mice using cloned gene probes and microsatellite markers from this region. No recombinants were observed between Cmv1 and the NKC-associated Ly49 and musNKR-P1 multigene families, nor the Kap locus, nor with 7 microsatellite markers, indicating that Cmv1 is closely linked (<1 cM) to all of these markers. Analysis of the genotype of the MCMV-susceptible BXD8 RI strain around the NKC region revealed that it had C57BL/6J alleles at microsatellite markers immediately proximal and distal to Cmv1. This suggests that the Cmv1{sup s} phenotype of this strain is due to a germ-line mutation. Thus, the close linkage of Cmv1 to the Ly49 and musNK-R-P1 multigene families suggests that it may represent an NK cell recognition structure encoded in the NKC region. 37 refs., 3 figs., 1 tab.

  3. Physical and transcript map of the autosomal dominant colobomatous microphthalmia locus on chromosome 15q12-q15 and refinement to a 4.4 Mb region.

    PubMed

    Michon, Laetitia; Morlé, Laurette; Bozon, Muriel; Duret, Laurent; Zech, Jean-Christophe; Godet, Jacqueline; Plauchu, Henry; Edery, Patrick

    2004-07-01

    Congenital microphthalmia is a developmental disorder characterized by shortened axial length of the eye. We have previously mapped the gene responsible for autosomal dominant colobomatous microphthalmia in a 5-generation family to chromosome 15q12-q15. Here, we set up a physical and transcript map of the 13.8 cM critical region, flanked by loci D15S1002 and D15S1040. Physical mapping and genetic linkage analysis using 20 novel polymorphic markers allowed the refinement of the disease locus to two intervals in close vicinity, namely a centromeric interval, bounded by microsatellite DNA markers m3-m17, and a telomeric interval, m76-m24, encompassing respectively 1.9 and 2.5 Mb. Moreover, we excluded three candidate genes, CKTSF1B1, KLF13 and CX36. Finally, although a phenomenon of anticipation was suggested by phenotypic and pedigree data, no abnormal expansion of three trinucleotide repeats mapping to the refine interval was found in affected individuals. PMID:15083168

  4. Kabuki syndrome is not caused by a microdeletion in the DiGeorge/velocardiofacial chromosomal region within 22q11.2

    SciTech Connect

    Li, M.; Zackai, E.H.; Kaplan, P.; Driscoll, D.A.; Niikawa, Norio

    1996-10-16

    Kabuki syndrome (KS) or Niikawa-Kuroki syndrome is a sporadic disorder characterized by postnatal growth retardation, developmental delay, mild to moderate retardation, and a characteristic facial appearance. Cardiovascular defects, clefts of the lip, palate, or both, and musculoskeletal abnormalities occur in about 50% of patients with KS. The cause of this multiple congenital anomaly syndrome is unknown, and investigators have speculated that KS is a contiguous gene-deletion syndrome. Based on the presence of congenital heart defects in patients with KS, it was suggested that this disorder might share a common cause with the 22q11 deletion syndromes. A preliminary study of 2 patients with KS failed to detect a deletion within 22q11. We report the results of fluorescence in situ hybridization with cosmid probes for loci D22S75 (N25) and D22S259 (1132) within the DiGeorge chromosomal region (DGCR) on metaphase spreads from an additional 5 patients, 2 non-Japanese and 3 Japanese, with KS. None of the 5 had deletions at either locus. It is unlikely that KS is caused by a deletion within 22q11. 16 refs.

  5. The leukemogenic t(8;21) fusion protein AML1-ETO controls ribosomal RNA genes and associates with nucleolar organizing regions at mitotic chromosomes

    PubMed Central

    Bakshi, Rachit; Zaidi, Sayyed K.; Pande, Sandhya; Hassan, Mohammad Q.; Young, Daniel W.; Lian, Jane B.; van Wijnen, Andre J.; Stein, Janet L.; Stein, Gary S.

    2010-01-01

    SUMMARY RUNX1/AML1 is required for definitive hematopoiesis and is frequently targeted by chromosomal translocation in acute myeloid leukemias (AML). The t(8;21) related AML1-ETO fusion protein blocks differentiation of myeloid progenitors. Here, we show by immunofluorescence microscopy that during interphase, endogenous AML1-ETO localizes to nuclear microenvironments distinct from those containing native RUNX1/AML1 protein. At mitosis, we clearly detect binding of AML1-ETO to nucleolar organizing regions (NORs) in AML derived Kasumi-1 cells and binding of RUNX1/AML1 to NORs in Jurkat cells. Both RUNX1/AML1 and AML1-ETO occupy ribosomal DNA repeats during interphase, as well as interact with the endogenous RNA Pol I transcription factor UBF-1. Promoter cytosine methylation analysis indicates that RUNX1/AML1 binds to rDNA repeats that are more highly CpG methylated than those bound by AML1-ETO. Down-regulation by RNA interference reveals that RUNX1/AML1 negatively regulates rDNA transcription, while AML1-ETO is a positive regulator in Kasumi-1 cells. Taken together, our findings identify a novel role for the leukemia-related AML1-ETO protein in epigenetic control of cell growth through upregulation of RNA Pol I-mediated ribosomal gene transcription, consistent with the hyper-proliferative phenotype of myeloid cells in AML patients. PMID:19001502

  6. Detection of Chromosome X;18 Breakpoints and Translocation of the Xq22.3;18q23 Regions Resulting in Variable Fertility Phenotypes

    PubMed Central

    Szvetko, Attila; Martin, Nicole; Joy, Chris; Hayward, Andrea; Watson, Bob; Cary, Andrew; Withers, Stephen

    2012-01-01

    We describe a familial pattern of gonosomal-autosomal translocation between the X and 18 chromosomes, balanced and unbalanced forms, in male and female siblings. The proposita was consulted for hypergonadotropic hypogonadism. Karyotype analysis revealed a balanced 46, X, t(X;18)(q22.3;q23) genotype. The sister of the proband presented with oligomenorrhea with irregular menses and possesses an unbalanced form of the translocation 46, X, der(X), t(X;18)(q22.3;q23). The brother of the proband was investigated and was found to possess the balanced form of the same translocation, resulting in disrupted spermatogenesis. Maternal investigation revealed the progenitor karyotype 46, X, t(X;18)(q22.3;q23). Maternal inheritance and various genomic events contributed to the resultant genotypes. Primary infertility was initially diagnosed in all progeny; however, the male individual recently fathered twins. We briefly review the mechanisms associated with X;18 translocations and describe a pattern of inheritance, where breakpoints and translocation of the Xq22.3;18q23 regions have resulted in variable fertility. PMID:23074692

  7. Detection of chromosome x;18 breakpoints and translocation of the xq22.3;18q23 regions resulting in variable fertility phenotypes.

    PubMed

    Szvetko, Attila; Martin, Nicole; Joy, Chris; Hayward, Andrea; Watson, Bob; Cary, Andrew; Withers, Stephen

    2012-01-01

    We describe a familial pattern of gonosomal-autosomal translocation between the X and 18 chromosomes, balanced and unbalanced forms, in male and female siblings. The proposita was consulted for hypergonadotropic hypogonadism. Karyotype analysis revealed a balanced 46, X, t(X;18)(q22.3;q23) genotype. The sister of the proband presented with oligomenorrhea with irregular menses and possesses an unbalanced form of the translocation 46, X, der(X), t(X;18)(q22.3;q23). The brother of the proband was investigated and was found to possess the balanced form of the same translocation, resulting in disrupted spermatogenesis. Maternal investigation revealed the progenitor karyotype 46, X, t(X;18)(q22.3;q23). Maternal inheritance and various genomic events contributed to the resultant genotypes. Primary infertility was initially diagnosed in all progeny; however, the male individual recently fathered twins. We briefly review the mechanisms associated with X;18 translocations and describe a pattern of inheritance, where breakpoints and translocation of the Xq22.3;18q23 regions have resulted in variable fertility. PMID:23074692

  8. A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression

    PubMed Central

    Farrell, John J.; Sherva, Richard M.; Chen, Zhi-yi; Luo, Hong-yuan; Chu, Benjamin F.; Ha, Shau Yin; Li, Chi Kong; Lee, Anselm C. W.; Li, Rever C. H.; Li, Chi Keung; Yuen, Hui Leung; So, Jason C. C.; Ma, Edmond S. K.; Chan, Li Chong; Chan, Vivian; Sebastiani, Paola; Farrer, Lindsay A.; Baldwin, Clinton T.; Steinberg, Martin H.

    2011-01-01

    Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations. PMID:21385855

  9. Methods and compositions for chromosome-specific staining

    DOEpatents

    Gray, Joe W.; Pinkel, Daniel

    2003-07-22

    Methods and compositions for chromosome-specific staining are provided. Compositions comprise heterogenous mixtures of labeled nucleic acid fragments having substantially complementary base sequences to unique sequence regions of the chromosomal DNA for which their associated staining reagent is specific. Methods include methods for making the chromosome-specific staining compositions of the invention, and methods for applying the staining compositions to chromosomes.

  10. Organization of the bacterial chromosome.

    PubMed Central

    Krawiec, S; Riley, M

    1990-01-01

    Recent progress in studies on the bacterial chromosome is summarized. Although the greatest amount of information comes from studies on Escherichia coli, reports on studies of many other bacteria are also included. A compilation of the sizes of chromosomal DNAs as determined by pulsed-field electrophoresis is given, as well as a discussion of factors that affect gene dosage, including redundancy of chromosomes on the one hand and inactivation of chromosomes on the other hand. The distinction between a large plasmid and a second chromosome is discussed. Recent information on repeated sequences and chromosomal rearrangements is presented. The growing understanding of limitations on the rearrangements that can be tolerated by bacteria and those that cannot is summarized, and the sensitive region flanking the terminator loci is described. Sources and types of genetic variation in bacteria are listed, from simple single nucleotide mutations to intragenic and intergenic recombinations. A model depicting the dynamics of the evolution and genetic activity of the bacterial chromosome is described which entails acquisition by recombination of clonal segments within the chromosome. The model is consistent with the existence of only a few genetic types of E. coli worldwide. Finally, there is a summary of recent reports on lateral genetic exchange across great taxonomic distances, yet another source of genetic variation and innovation. PMID:2087223

  11. Analysis of chromosome 21 yeast artificial chromosome (YAC) clones

    SciTech Connect

    Tassone, F. A. Gemelli School of Medicine, Rome ); Cheng, S.; Gardiner, K. )

    1992-12-01

    Chromosome 21 contains genes relevant to several important diseases. Yeast artificial chromosome (YAC) clones, because they span >100 kbp, will provide attractive material for initiating searches for such genes. Twenty-two YAC clones, each of which maps to a region of potential relevance either to aspects of the Down syndrome phenotype or to one of the other chromosome 21-associated genetic diseases, have been analyzed in detail. Clones total [approximately]6,000 kb and derive from all parts of the long arm. Rare restriction-site maps have been constructed for each clone and have been used to determine regional variations in clonability, methylation frequency, CpG island density, and CpG island frequency versus gene density. This information will be useful for the isolation and mapping of new genes to chromosome 21 and for walking in YAC libraries. 48 refs., 3 figs., 4 tabs.

  12. Chromosome Microarray.

    PubMed

    Anderson, Sharon

    2016-01-01

    Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed. PMID:27276104

  13. Chromosomal Minimal Critical Regions in Therapy-Related Leukemia Appear Different from Those of De Novo Leukemia by High-Resolution aCGH

    PubMed Central

    Itzhar, Nathalie; Dessen, Philippe; Toujani, Saloua; Auger, Nathalie; Preudhomme, Claude; Richon, Catherine; Lazar, Vladimir; Saada, Véronique; Bennaceur, Anelyse; Bourhis, Jean Henri; de Botton, Stéphane; Bernheim, Alain

    2011-01-01

    Therapy-related acute leukemia (t-AML), is a severe complication of cytotoxic therapy used for primary cancer treatment. The outcome of these patients is poor, compared to people who develop de novo acute leukemia (p-AML). Cytogenetic abnormalities in t-AML are similar to those found in p-AML but present more frequent unfavorable karyotypes depending on the inducting agent. Losses of chromosome 5 or 7 are observed after alkylating agents while balanced translocations are found after topoisomerase II inhibitors. This study compared t-AML to p-AML using high resolution array CGH in order to find copy number abnormalities (CNA) at a higher resolution than conventional cytogenetics. More CNAs were observed in 30 t-AML than in 36 p-AML: 104 CNAs were observed with 63 losses and 41 gains (mean number 3.46 per case) in t-AML, while in p-AML, 69 CNAs were observed with 32 losses and 37 gains (mean number of 1.9 per case). In primary leukemia with a previously “normal” karyotype, 18% exhibited a previously undetected CNA, whereas in the (few) t-AML with a normal karyotype, the rate was 50%. Several minimal critical regions (MCRs) were found in t-AML and p-AML. No common MCRs were found in the two groups. In t-AML a 40kb deleted MCR pointed to RUNX1 on 21q22, a gene coding for a transcription factor implicated in frequent rearrangements in leukemia and in familial thrombocytopenia. In de novo AML, a 1Mb MCR harboring ERG and ETS2 was observed from patients with complex aCGH profiles. High resolution cytogenomics obtained by aCGH and similar techniques already published allowed us to characterize numerous non random chromosome abnormalities. This work supports the hypothesis that they can be classified into several categories: abnormalities common to all AML; those more frequently found in t-AML and those specifically found in p-AML. PMID:21339820

  14. A duplicated region is responsible for the poly(ADP-ribose) polymerase polymorphism, on chromosome 13, associated with a predisposition to cancer

    SciTech Connect

    Lyn, D.; Cherney, B.W.; Lupold, S.; Smulson, M. ); Lalande, M. Harvard Medical School, Boston, MA ); Berenson, J.R.; Lichtenstein, A. Veterans Administration Medical Center, Los Angeles, CA ); Bhatia, K.G. )

    1993-01-01

    The poly(ADP-ribose) polymerase (PADPRP) gene (13q33-qter) depicts a two-allele (A/B) polymorphism. In the noncancer population, the frequency of the B allele is higher among blacks than among whites. Since the incidence of multiple myeloma and prostate and lung cancer is higher in the US black population, the authors have analyzed the B-allele frequency in germ-line DNA to determine whether the PADPRP gene correlates with a polymorphic susceptibility to these diseases. For multiple myeloma and prostate cancer, an increased frequency of the B allele appeared to be striking only in black patients. In contrast, the distribution of the B allele in germ-line DNA did not differ among white patients with these diseases, when compared with the control group. An elevated B-allele frequency was also found in germ-line DNA in blacks with colon cancer. These observations suggest that the PADPRP polymorphism may provide a valid marker for a predisposition to these cancers in black individuals. To determine the genomic structure of the polymorphic PADPRP sequences, a 2.68-kb HindIII clone was isolated and sequenced from a chromosome 13-enriched library. Sequence analysis of this clone (A allele) revealed a close sequence similarity (91.8%) to PADPRP cDNA (1q42) and an absence of introns, suggesting that the gene on 13q exists as a processed pseudogene. A 193-bp conserved duplicated region within the A allele was identified as the source of the polymorphism. The nucleotide differences between the PADPRP gene on chromosome 13 and related PADPRP genes were exploited to develop oligonucleotides that can detect the difference between the A/B genotypes in a PCR. This PCR assay offers the opportunity for analyzing additional black cancer patients, to determine how the PADPRP processed pseudogene or an unidentified gene that cosegregates with the PADPRP gene might be involved with the development of malignancy. 16 refs., 6 figs., 1 tab.

  15. Gene organization of the pregnancy-specific glycoprotein region on human chromosome 19: Assembly and analysis of a 700-kb cosmid contig spanning the region

    SciTech Connect

    Olsen, A.; Nelson, D.; Gordon, L.

    1994-10-01

    The pregnancy-specific glycoprotein (PSG) gene family consists of 11 closely related genes that form a subgroup of the carcinoembryonic antigen (CEA) gene family on 19q13.2. Using a high-resolution restriction fragment fingerprinting technique, we have assembled 256 cosmids from the PSG region into a single 700-kb contig. Fluorescence in situ hybridization to sperm pronuclei and cosmid walking experiments indicated that this PSG contig was directly telomeric of CGM8 at the telomeric end of the CEA subgroup gene cluster. Detailed restriction mapping and hybridization with gene-specific probes indicated that the order of the 11 previously identified PSG genes is cen - PSG3 - PSG8 - PSG12 - PSG1 - PSG6 - PSG7 - PSG13 - PSG2 - PSG5 - PSG4 - PSG11 - tel. The CEA subgroup gene CGM11 is located at the telomeric end of the PSG gene cluster. The PSG gene are all oriented in tandem with the 5{prime}-3{prime} direction of transcription from telomere to centromere. The detailed map also led to the identification of seven new CEA family genes in the region. One of these (CGM12), located between CGM8 and PSG3, is a member of the CEA subgroup. The remaining six (CGM13 through CGM18) are interspersed among the PSG genes and appear to form a third distinct subgroup within the CEA gene family. 34 refs., 6 figs.

  16. Chromosome Analysis

    NASA Technical Reports Server (NTRS)

    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.

  17. Structure and function of the region of the replication origin of the Bacillus subtilis chromosome. IV. Transcription of the oriC region and expression of DNA gyrase genes and other open reading frames.

    PubMed Central

    Ogasawara, N; Moriya, S; Yoshikawa, H

    1985-01-01

    We have determined nucleotide sequence of some 10,000 base pairs (bp) in the oriC region of the Bacillus subtilis chromosome. Initiation sites of transcription from this region were determined in vivo by the S1-mapping method. Five major initiation sites were found in the leader sequences of five open reading frames (ORF) deduced from the nucleotide sequence. The sixth site is located inside the ORF323("recF"). Putative promoters were found for each transcript. Function of these promoters was demonstrated in Escherichia coli by the Maxi-cell method using appropriate fragments cloned in pBR vectors. Based on these results, genes in 10,000 bp oriC region are divided into 4 transcriptional units. GyrB composes one unit with two other ORFs, while gyrA constitutes a single unit by itself. The promoters for ORF446("dnaA") and ORF378("dnaN") are located within the putative signal sequences for oriC. Transcription from these promoters is dependent on a dna-initiation gene, dnaB. Images PMID:2987848

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

    PubMed

    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; Gabor