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Sample records for 4q25 chromosomal locus

  1. Independent Susceptibility Markers for Atrial Fibrillation on Chromosome 4q25

    PubMed Central

    Lubitz, Steven A.; Sinner, Moritz F.; Lunetta, Kathryn L.; Makino, Seiko; Pfeufer, Arne; Rahman, Rosanna; Veltman, Caroline E.; Barnard, John; Bis, Joshua C.; Danik, Stephan P.; Sonni, Akshata; Shea, Marisa A.; del Monte, Federica; Perz, Siegfried; Müller, Martina; Peters, Annette; Greenberg, Steven M.; Furie, Karen L.; van Noord, Charlotte; Boerwinkle, Eric; Stricker, Bruno H. Ch.; Witteman, Jacqueline; Smith, Jonathan D.; Chung, Mina K.; Heckbert, Susan R.; Benjamin, Emelia J.; Rosand, Jonathan; Arking, Dan E.; Alonso, Alvaro; Kääb, Stefan; Ellinor, Patrick T.

    2010-01-01

    Background Genetic variants on chromosome 4q25 are associated with atrial fibrillation (AF). We sought to determine whether there is more than one susceptibility signal at this locus. Methods and Results 34 haplotype-tagging single nucleotide polymorphisms (SNPs) at the 4q25 locus were genotyped in 790 case and 1,177 control subjects from Massachusetts General Hospital and tested for association with AF. We replicated SNPs associated with AF after adjustment for the most significantly associated SNP in 5,066 case and 30,661 referent subjects from the German Competence Network for Atrial Fibrillation, Atherosclerosis Risk in Communities Study, Cleveland Clinic Lone AF study, Cardiovascular Health Study, and Rotterdam Study. All subjects were of European ancestry. A multimarker risk score comprised of SNPs tagging distinct AF susceptibility signals was constructed and tested for association with AF, and all results were meta-analyzed. The previously reported SNP, rs2200733, was most significantly associated with AF (minor allele odds ratio 1.80, 95%CI 1.50-2.15, P=1.2×10−20) in the discovery sample. Adjusting for rs2200733 genotype revealed 2 additional susceptibility signals marked by rs17570669 and rs3853445. A graded risk of AF was observed with an increasing number of AF risk alleles at SNPs tagging these 3 susceptibility signals. Conclusions We identified 2 novel AF susceptibility signals on chromosome 4q25. Consideration of multiple susceptibility signals at chromosome 4q25 identifies individuals with an increased risk of AF and may localize regulatory elements at the locus with particular biological relevance in the pathogenesis of AF. PMID:20733104

  2. Mapping of a gene for long QT syndrome to chromosome 4q25-27

    SciTech Connect

    Schott, J.J.; Charpentier, F.; Peltier, S.

    1995-11-01

    Long QT syndrome (LQTS) is a heterogeneous inherited disorder causing syncope and sudden death from ventricular arrhythmias. A first locus for this disorder was mapped to chromosome 11p15.5. However, locus heterogeneity has been demonstrated in several families, and two other loci have recently been located on chromosomes 7q35-36 and 3p21-24. We used linkage analysis to map the locus in a 65-member family in which LQTS was associated with more marked sinus bradycardia than usual, leading to sinus node dysfunction. Linkage to chromosome 11p15.5, 7q35-36, or 3p21-24 was excluded. Positive linkage was obtained for markers located on chromosome 4q25-27. A maximal LOD score of 7.05 was found for marker D4S402. The identification of a fourth locus for LQTS confirms its genetic heterogeneity. Locus 4q25-27 is associated with a peculiar phenotype within the LQTS entity. 42 refs., 4 figs., 3 tabs.

  3. Association between Variants on Chromosome 4q25, 16q22 and 1q21 and Atrial Fibrillation in the Polish Population

    PubMed Central

    Kiliszek, Marek; Franaszczyk, Maria; Kozluk, Edward; Lodzinski, Piotr; Piatkowska, Agnieszka; Broda, Grażyna; Ploski, Rafal; Opolski, Grzegorz

    2011-01-01

    Background Genome-wide studies have shown that polymorphisms on chromosome 4q25, 16q22 and 1q21 correlate with atrial fibrillation (AF). However, the distribution of these polymorphisms differs significantly among populations. Objective To test the polymorphisms on chromosome 4q25, 16q22 and 1q21 in a group of patients (pts) that underwent catheter ablation of AF. Methods Four hundred and ten patients with AF that underwent pulmonary vein isolation were included in the study. Control group (n = 550) was taken from healthy population, matched for age, sex and presence of hypertension. All participants were genotyped for the presence of the rs2200733, rs10033464, rs17570669, rs3853445, rs6838973 (4q25), rs7193343 (16q22) and rs13376333 (1q21) polymorphisms. Results All the polymorphisms tested (except rs17570669) correlated significantly with AF in univariate analysis (p values between 0.039 for rs7193343 and 2.7e-27 for rs2200733), with the odds ratio (OR) 0.572 and 0.617 for rs3853445 and rs6838973, respectively (protective role) and OR 1.268 to 3.52 for the other polymorphisms. All 4q25 SNPs tested but rs3853445 were independently linked with AF in multivariate logistic regression analysis. In haplotype analysis six out of nine 4q25 haplotypes were significantly linked with AF. The T allele of rs2200733 favoured increased number of episodes of AF per month (p = 0.045) and larger pulmonary vein diameter (recessive model, p = 0.032). Conclusions Patients qualified for catheter ablation of AF have a significantly higher frequency of 4q25, 16q22 and 1q21 variants than the control group. The T allele of rs2200733 favours larger pulmonary veins and increased number of episodes of AF. PMID:21760908

  4. A second locus for Rieger syndrome maps to chromosome 13q14.

    PubMed Central

    Phillips, J. C.; del Bono, E. A.; Haines, J. L.; Pralea, A. M.; Cohen, J. S.; Greff, L. J.; Wiggs, J. L.

    1996-01-01

    Rieger syndrome is a genetically and phenotypically heterogeneous disorder typically characterized by malformations of the eyes, teeth, and umbilicus. The syndrome is inherited as an autosomal dominant trait and exhibits significant variable expressivity. One locus associated with this disorder has been mapped to 4q25. Using a large four-generation pedigree, we have identified a second locus for Rieger syndrome located on chromosome 13q14. PMID:8751862

  5. A Rare Recurrent 4q25 Proximal Deletion Not Involving the PITX2 Gene: A Genomic Disorder Distinct from Axenfeld-Rieger Syndrome.

    PubMed

    Heithaus, Jennifer L; Twyman, Kimberly A; Batanian, Jacqueline R

    2016-07-01

    Haploinsufficient microdeletions within chromosome 4q25 are often associated with Axenfeld-Rieger syndrome. A de novo 4q25 deletion, 675 kb proximal to PITX2, has previously been reported once in an adult patient. The patient did not have Axenfeld-Rieger anomaly, but instead had intellectual disability and a complex behavioral phenotype with withdrawn, stereotypic, and ritualistic behavior. Array comparative genome hybridization demonstrated a smaller, overlapping 4q25 deletion in a 2-year-old patient and his mother, both having significant phenotypic overlap with the initially reported patient. All 3 patients have distinct facial features (including mild hypotelorism and subtle mandibular asymmetry), developmental delay, and complex behavioral difficulties. A genotype-phenotype correlation narrows the shared phenotype to a common COL25A1 gene aberration and proposes that the concurrent EGF gene loss has a significant impact on the phenotypic severity. Overall, our patients provide data to support the existence of a novel 4q25 proximal deletion syndrome. PMID:27587989

  6. Chromosomal locus for staphylococcal enterotoxin B.

    PubMed Central

    Shafer, W M; Iandolo, J J

    1978-01-01

    The genetic locus of staphylococcal enterotoxin B (SEB) was investigated in the Staphylococcus aureus food-poisoning isolates, strains S6 and 277. Direct neutral sucrose gradient centrifugation analysis of sodium dodecyl sulfate-sodium chloride-mediated cleared lysates demonstrated that strain S6 contained a single 37S plasmid. Transductional analysis revealed that the 37S plasmid in S6 encoded for cadmium resistance (Cad) but not SEB. Additionally, elimination of cadmium resistance in S6 provided a plasmid-negative derivative that produced SEB at the same level as the parent. Examination of strain 277 showed two plasmids, a 37S species encoding for penicillin resistance (Penr) and a 21S species containing the gene(s) responsible for tetracycline resistance (Tetr). Elimination of the 37S, penr plasmid in 277 had no effect on SEB production, whereas introduction of the 21S tetr plasmid via transformation into strain 8325 (SEB--) did not confer enterotoxigenesis upon the transformants. The data obtained in this investigation suggest that the SEB gene(s) in these food-poisoning isolates of S. aureus is chromosomal. Images PMID:669796

  7. Interstitial deletions 4q21.1q25 and 4q25q27: Phenotypic variability and relation to Rieger anomaly

    SciTech Connect

    Kulharya, A.S.; Schneider, N.R.; Tonk, V.

    1995-01-16

    We describe clinical and chromosomal findings in two patients with del(4q). Patient 1, with interstitial deletion (4)(q21.1q25), had craniofacial and skeletal anomalies and died at 8 months hydrocephalus. Patient 2, with interstitial deletion (4)(q25q27), had craniofacial and skeletal anomalies with congenital hypotonia and developmental delay. These patients shared certain manifestations with other del(4q) patients but did not have Rieger anomaly. Clinical variability among patients with interstitial deletions of 4q may be related to variable expression, variable deletion, or imprinting of genes within the 4q region. 15 refs., 4 figs., 1 tab.

  8. The 4q25, 1q21, and 16q22 polymorphisms and recurrence of atrial fibrillation after pulmonary vein isolation

    PubMed Central

    Kozluk, Edward; Franaszczyk, Maria; Lodzinski, Piotr; Piatkowska, Agnieszka; Ploski, Rafal; Opolski, Grzegorz

    2016-01-01

    Introduction The efficacy of pulmonary vein isolation (PVI) in atrial fibrillation (AF) is well documented. Several single nucleotide polymorphisms (SNPs) are associated with AF, mainly in the 4q25 locus, but also in 16q22 and 1q21. The aim of our study was to test the association between those SNPs and short- and long-term results of PVI. Material and methods Patients with AF who underwent PVI between 2006 and 2009 were included in the study. Pulmonary vein isolation was performed using a 4-mm non-irrigated ablation catheter, circular mapping catheter, and the LocaLisa system. All patients were genotyped for the 4q25, 16q22, and 1q21 SNPs. Results Two-hundred and thirty-eight patients were included. The median follow-up was 45 months. Six-month efficacy was 59.7%. None of the polymorphisms was linked with the risk of AF recurrence after 6 months in univariate analysis. In multivariate analysis rs2200733 in the recessive model was linked significantly with AF recurrence (odds ratio 1.87, p = 0.008). None of the polymorphisms predicted AF recurrence in long-term follow-up. Conclusions There is a trend in the relationship between TT genotype of the rs2200733 polymorphism and increased rate of AF recurrence after PVI in short-term (6 months) follow-up. None of the tested SNPs 4q25, 16q22, and 1q21 correlated with the results of a single AF ablation in long-term follow-up. PMID:26925117

  9. Search for a schizophrenia susceptibility locus of human chromosome 22

    SciTech Connect

    Coon, H.; Hoff, M.; Holik, J.

    1994-06-15

    We used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib-pair analysis was inconclusive. Affected Pedigree Member (APM) analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non-significant results for the three different weighting functions. 18 refs., 1 fig., 7 tabs.

  10. Quantitative trait locus for reading disability on chromosome 6

    SciTech Connect

    Cardon, L.R. |; Smith, S.D.; Kimberling, W.J.; Fulker, D.W.; DeFries, J.C.; Pennington, B.F.

    1994-10-14

    Interval mapping of data from two independent samples of sib pairs, at least one member of whom was reading disabled, revealed evidence for a quantitative trait locus (QTL) on chromosome 6. Results obtained from analyses of reading performance from 114 sib pairs genotyped for DNA markers localized the QTL to 6p21.3. Analyses of corresponding data from an independent sample of 50 dizygotic twin pairs provided evidence for linkage to the same region. In combination, the replicate samples yielded a x{sup 2} value of 16.73 (P = 0.0002). Examination of twin and kindred siblings with more extreme deficits in reading performance yielded even stronger evidence for a QTL (x{sup 2} = 27.35, P < 0.00001). The position of the QTL was narrowly defined with a 100:1 confidence interval to a 2-centimorgan region within the human leukocyte antigen complex. 23 refs., 4 figs.

  11. Genetic homogeneity at the Friedreich Ataxia locus on chromosome 9

    PubMed Central

    Chamberlain, Susan; Shaw, Jacqui; Wallis, Julie; Rowland, Alison; Chow, Larry; Farrall, Martin; Keats, Bronya; Richter, Andrea; Roy, Madeleine; Melancon, Serge; Deufel, Thomas; Berciano, José; Williamson, Robert

    1989-01-01

    Classical Friedreich ataxia, a progressive, neurodegenerative disorder involving both the central and peripheral nervous systems, has been subclassified according to the observed clinical heterogeneity. The variations in the age at onset and in the spectrum and severity of symptoms have previously been interpreted as evidence of genetic heterogeneity. We have studied the linkage between the disorder and closely linked DNA markers in families of distinct ethnic origins, including the “typical” French–Canadians and the Acadian population of Louisiana. The disease in these two populations, both of continental French origin, has a very similar initial clinical picture. However, a marked difference in the rate of progression of the obligatory symptoms after 10 years of apparent disease is observed. A total of 553 individuals from 80 families with 202 affected members have been typed with the chromosome 9 marker MCT112, which we have previously shown to be closely linked to the disease locus. Evidence for linkage was observed in all families with the generation of a combined total lod score of 25.09 at a recombination fraction of θ = .00, providing strong evidence for genetic homogeneity at this locus for the classical form of this disease. PMID:2929596

  12. A familial venous malformation locus is on chromosome 9p

    SciTech Connect

    Boon, L.M.; Mulliken, J.B.; Vikkula, M.

    1994-09-01

    Venous malformation is the most common vascular malformation affecting 0.2% of the population. Depending upon size and location, these slow-flow lesions may cause pain, anatomic distortion and threaten life. Most venous malformations occur sporadically and present as solitary lesions. For this reason, determining their pathogenic bases has proven elusive. However, venous malformations also occur in several rare syndromes, some of which demonstrate Mendelian inheritance. As a first step towards identifying the pathogenic bases for these lesions, we have mapped a locus for an autosomal dominant disorder in a three generation family that manifests as multiple cutaneous and mucosal venous malformations. This locus lies within a 24.5 cM interval on chromosome 9p, defined by the markers D9S157 and D9S163. A maximum LOD score of 4.11 at {theta} = 0.05 is obtained with several markers within the interval. The interferon gene cluster, which has previously been implicated in angiogenesis, and the multiple tumor suppressor gene, responsible for several types of malignant tumors, also lie within this interval and are potential candidates.

  13. A locus regulating bronchial hyperresponsiveness maps to chromosome 5q

    SciTech Connect

    Levitt, R.C.; Meyers, D.A.; Bleecker, E.R.

    1994-09-01

    Bronchial hyperresponsiveness (BHR) is one of the hallmarks of asthma. BHR correlates well with asthmatic symptoms and the response to treatment. Moreover, BHR appears to be closely related to airways inflammation. Numerous studies have demonstrated a familial aggregation; however, this phenotype is not likely inherited as a simple Mendelian trait. BHR is also closely associated with total serum IgE levels, as are allergy and asthma. We studied 92 families from Northern Holland ascertained through a parent with asthma who were originally studied between 1962-1970. Since there are a number of candidate genes on chromosome 5q potentially important in producing BHR, families were genotyped for markers in this region. These genes regulate IgE production and the cellular elements that are likely involved in inflammation associated with BHR, allergy and asthma. They include IL-4, IL-3, IL-5, IL-9, IL-12, IL-13 and GM-CSF. Linkage of BHR with markers on 5q was tested using a model free sib-pair method. The data suggest a locus for BHR maps near the cytokine gene cluster on 5q. This region appears critical in producing susceptibility to BHR and possibly to asthma.

  14. Polymorphic Chromosomes Bearing the Tox2 Locus in Cochliobolus carbonum Behave as Homologs during Meiosis

    PubMed Central

    Canada, S. R.; Dunkle, L. D.

    1997-01-01

    The HTS1 gene in the Tox2 locus of the fungal pathogen Cochliobolus carbonum race 1 is required for synthesis of a host-selective phytotoxin and for increased virulence on susceptible genotypes of maize. The locus is present in race 1 isolates but absent from isolates of the other races, which do not produce the toxin. By pulsed-field gel electrophoresis and Southern analysis with HTS1 sequences and chromosome-specific markers, the HTS1 gene was detected on a 4-Mb chromosome in one group of isolates and on a 2.3-Mb chromosome in another group, which lacked the 4-Mb chromosome. A chromosome-specific marker from C. heterostrophus hybridized to a 2.3-Mb chromosome in non-toxin-producing isolates and in toxin-producing isolates, including those with a 4-Mb chromosome. A marker from C. carbonum hybridized to the 4-Mb chromosome, but in isolates lacking the 4-Mb chromosome, this marker hybridized to a smaller, 2.0-Mb chromosome. Thus, the Tox2 locus is on different chromosomes in different groups of race 1 isolates. Single ascospore progeny from crosses between isolates having HTS1 on different chromosomes were analyzed for toxin-producing ability, virulence, and the presence and chromosomal location of HTS1. All progeny produced HC toxin in culture, incited race 1-type lesions on susceptible maize genotypes, and contained HTS1 sequences, as determined by PCR amplification with gene-specific primers. Analysis of the chromosomal complements of several progeny indicated that they all had only one Tox2-containing chromosome. Thus, despite their differences in size, these chromosomes behave as homologs during meiosis and may have arisen by a translocation. PMID:16535561

  15. Genetic heterogeneity in benign familial neonatal convulsions: Identification of a new locus on chromosome 8q

    SciTech Connect

    Lewis, T.B.; Leach, R.J.; O'Connell, P.; Ryan, S.G. ); Ward, K. )

    1993-09-01

    The syndrome of benign familial neonatal convulsions (BFNC) is a rare autosomal dominant disorder characterized by unprovoked seizures in the first weeks of life. One locus for BFNC has been mapped to chromosome 20 in several pedigrees, but the authors have excluded linkage to chromosome 20 in one large kindred. In order to identify this novel BFNC locus, dinucleotide repeat markers distributed throughout the genome were used to screen this family. Maximum pairwise LOD scores of 4.43 were obtained with markers D8S284 and D8S256 on chromosome 8q. Multipoint analysis placed the BFNC locus in the interval spanned by D8S198-D8S274. This study establishes the presence of a new BFNC locus and confirms genetic heterogeneity of this disorder. 26 refs., 3 figs., 1 tab.

  16. Construction of a yeast artificial chromosome contig encompassing the chromosome 14 Alzheimer`s disease locus

    SciTech Connect

    Sharma, V.; Bonnycastle, L.; Poorkai, P.

    1994-09-01

    We have constructed a yeast artificial chromosome (YAC) contig of chromosome 14q24.3 which encompasses the chromosome 14 Alzheimer`s disease locus (AD3). Determined by linkage analysis of early-onset Alzheimer`s disease kindreds, this interval is bounded by the genetic markers D14S61-D14S63 and spans approximately 15 centimorgans. The contig consists of 29 markers and 74 YACs of which 57 are defined by one or more sequence tagged sites (STSs). The STS markers comprise 5 genes, 16 short tandem repeat polymorphisms and 8 cDNA clones. An additional number of genes, expressed sequence tags and cDNA fragments have been identified and localized to the contig by hybridization and sequence analysis of anonymous clones isolated by cDNA direct selection techniques. A minimal contig of about 15 YACs averaging 0.5-1.5 megabase in length will span this interval and is, at first approximation, in rough agreement with the genetic map. For two regions of the contig, our coverage has relied on L1/THE fingerprint and Alu-PCR hybridization data of YACs provided by CEPH/Genethon. We are currently developing sequence tagged sites from these to confirm the overlaps revealed by the fingerprint data. Among the genes which map to the contig are transforming growth factor beta 3, c-fos, and heat shock protein 2A (HSPA2). C-fos is not a candidate gene for AD3 based on the sequence analysis of affected and unaffected individuals. HSPA2 maps to the proximal edge of the contig and Calmodulin 1, a candidate gene from 4q24.3, maps outside of the region. The YAC contig is a framework physical map from which cosmid or P1 clone contigs can be constructed. As more genes and cDNAs are mapped, a highly resolved transcription map will emerge, a necessary step towards positionally cloning the AD3 gene.

  17. The tyrosinase-positive oculocutaneous albinism locus maps to chromosome 15q11. 2-q12

    SciTech Connect

    Ramsay, M.; Colman, M.A.; Stevens, G.; Zwane, E.; Kromberg, J.; Jenkins, T. ); Garral, M.

    1992-10-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA), an autosomal recessive disorder of the melanin biosynthetic pathway, is the most common type of albinism occurring worldwide. In southern African Bantu-speaking negroids it has an overall prevalence of about 1/3,900. Since the basic biochemical defect is unknown, a linkage study with candidate loci, candidate chromosomal regions, and random loci was undertaken. The ty-pos OCA locus was found to be linked to two arbitrary loci, D15S10 and D15S13, in the Prader-Willi/Angelman chromosomal region on chromosome 15q11.2-q12. The pink-eyed dilute locus, p, on mouse chromosome 7, maps close to a region of homology on human chromosome 15q, and we postulate that the ty-pos OCA and p loci are homologous. 43 refs., 2 figs., 1 tab.

  18. A radiation hybrid map of chromosome ID reveals synteny conservation at a wheat speciation locus.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The species cytoplasm specific (scs) genes affect nuclear-cytoplasmic interactions in interspecific hybrids. A radiation hybrid (RH) mapping population of 188 individuals was employed to refine the location of the scsae locus of Tritcum aestivum chromosome 1D. ‘Wheat Zapper’, a comparative genomic...

  19. A novel quantitative trait locus for Fusarium head blight resistance in chromosome 7A of wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A Chinese Spring-Sumai 3 chromosome 7A disomic substitution line (CS-Sumai 3-7ADSL) was reported to have a high level of Fusarium head blight (FHB) resistance for symptom spread within a spike (Type II) and low deoxynivalenol accumulation in infected kernels (Type III), but quantitative trait locus ...

  20. A locus on chromosome 7 determines myocardial cell necrosis and calcification (dystrophic cardiac calcinosis) in mice.

    PubMed Central

    Ivandic, B T; Qiao, J H; Machleder, D; Liao, F; Drake, T A; Lusis, A J

    1996-01-01

    Dystrophic cardiac calcinosis, an age-related cardiomyopathy that occurs among certain inbred strains of mice, involves myocardial injury, necrosis, and calcification. Using a complete linkage map approach and quantitative trait locus analysis, we sought to identify genetic loci determining dystrophic cardiac calcinosis in an F2 intercross of resistant C57BL/6J and susceptible C3H/HeJ inbred strains. We identified a single major locus, designated Dyscalc, located on proximal chromosome 7 in a region syntenic with human chromosomes 19q13 and 11p15. The statistical significance of Dyscalc (logarithm of odds score 14.6) was tested by analysis of permuted trait data. Analysis of BxH recombinant inbred strains confirmed the mapping position. The inheritance pattern indicated that this locus influences susceptibility of cells both to enter necrosis and to subsequently undergo calcification. Images Fig. 1 Fig. 3 PMID:8643601

  1. Comparative mapping of the Grpr locus on the X chromosomes of man and mouse

    SciTech Connect

    Maslen, G.Ll.; Boyd, Y. )

    1993-07-01

    The gastrin-releasing peptide receptor has been previously cloned from both humans and mice. The authors have mapped the mouse gastrin-releasing peptide receptor (Grpr) locus using a polymorphic CA[sub n] repeat located in the 5[prime] untranslated region of the gene and a Mus spretus/Mus musculus interspecific backcross. The Grpr locus mapped between the Pdha-1 and Amg loci on the mouse X chromosome. Studies in man indicate that GRPR maps to the Xp21.2-p22.3 region of the human X chromosome and not to the Xp11-q11 interval as previously reported. The assignment of the GRPR locus to the distal Xp region is supported by the comparative map position in the mouse. 25 refs., 3 figs.

  2. The epitheliogenesis imperfecta locus maps to equine chromosome 8 in American Saddlebred horses.

    PubMed

    Lieto, L D; Cothran, E G

    2003-01-01

    Epitheliogenesis imperfecta (EI) is a hereditary junctional mechanobullous disease that occurs in newborn American Saddlebred foals. The pathological signs of epitheliogenesis imperfecta closely match a similar disease in humans known as Herlitz junctional epidermolysis bullosa, which is caused by a mutation in one of the genes (LAMA3, LAMB3 and LAMC2) coding for the subunits of the laminin 5 protein (laminin alpha3, laminin beta3 and laminin gamma2). The LAMA3 gene has been assigned to equine chromosome 8 and LAMB3 and LAMC2 have been mapped to equine chromosome 5. Linkage disequilibrium between microsatellite markers that mapped to equine chromosome 5 and equine chromosome 8 and the EI disease locus was tested in American Saddlebred horses. The allele frequencies of microsatellite alleles at 11 loci were determined for both epitheliogenesis imperfecta affected and unaffected populations of American Saddlebred horses by genotyping and direct counting of alleles. These were used to determine fit to Hardy-Weinberg equilibrium for control and EI populations using Chi square analysis. Two microsatellite loci located on equine chromosome 8q, ASB14 and AHT3, were not in Hardy-Weinberg equilibrium in affected American Saddlebred horses. In comparison, all of the microsatellite markers located on equine chromosome 5 were in Hardy-Weinberg equilibrium in affected American Saddlebred horses. This suggested that the EI disease locus was located on equine chromosome 8q, where LAMA3 is also located. PMID:14970704

  3. Bardet-Biedl syndrome: Mapping of a new locus to chromosome 3 and fine-mapping of the chromosome 16 linked locus

    SciTech Connect

    Kwitek-Black, A.E.; Rokhlina, T.; Nishimura, D.Y.

    1994-09-01

    Bardet-Biedl syndrome (BBS) is a heterogeneous autosomal recessive disorder characterized by mental retardation, post-axial polydactyly, obesity, retinitis pigmentosa, and hypogonadism. Other features of this disease include renal and cardiovascular abnormalities and an increased incidence of hypertension and diabetes mellitus. The molecular etiology for BBS is not known. We previously linked BBS to chromosome 16q13 in a large inbred Bedouin family, and excluded this locus in a second large inbred Bedouin family. We now report linkage of this second family to markers on chromosome 3q, proving non-allelic, genetic heterogeneity in the Bedouin population. A third large inbred Bedouin family was excluded from the 3q and 16q BBS loci. In addition to the identification of a new BBS locus on chromosome 3, we have identified and utilized additional short tandem repeat polymorphisms (STRPs) in the 16q BBS region to narrow the candidate interval to 3 cM. Additional recombinant individuals will allow further refinement of the interval. Identification of genes causing BBS has the potential to provide insight into diverse genetic traits and disease processes including obesity, hypertension, diabetes, retinal degeneration, and abnormal limb, renal and cardiac development.

  4. Analysis of human chromosome 21 for a locus conferring susceptibility to Hirschsprung Disease

    SciTech Connect

    Bolk, S.; Duggan, D.J.; Chakravarti, A.

    1994-09-01

    It has been estimated that approximately 5% of patients diagnosed with Hirschsprung disease (HSCR), or aganglionic megacolon, have trisomy 21. Since the incidence of Hirschsprung disease is 1/5000 live births and the incidence of trisomy 21 is approximately 1/1000 live births, the observed occurrence of HSCR in trisomy 21 is fifty times higher than expected. We propose that at least one locus on chromosome 21 predisposes to HSCR. Although at fifty times elevated risk, only 1% of Down Syndrome cases have HSCR. Thus additional genes or genetic events are necessary for HSCR to manifest in patients with trisomy 21. Based on segregation analysis, Badner et al. postulated that recessive genes may be responsible for up to 80% of HSCR. We postulate that at least one such gene is on chromosome 21 and increased homozygosity for common recessive HSCR mutations may be one cause for the elevated risk of HSCR in cases of trisomy 21. To map such a chromosome 21 locus, we are searching for segments of human chromosome 21 which are identical by descent from the parent in whom non-disjunction occurred. These segments will arise either from meiosis I (followed by a crossover between the centromere and the locus) or from meiosis II (followed by no crossovers). Nine nuclear families with a proband diagnosed with HSCR and Down Syndrome have been genotyped for 18 microsatellite markers spanning human chromosome 21q. In all nine cases analyzed thus far, trisomy 21 resulted from maternal non-disjunction at meiosis I. At this point no single IBD region is apparent. Therefore, additional families are being ascertained and additional markers at high density are being genotyped to map the HSCR locus.

  5. The Huntington disease locus is most likely within 325 kilobases of the chromosome 4p telomere

    SciTech Connect

    Doggett, N.A.; Cheng, J.F.; Smith, C.L.; Cantor, C.R. )

    1989-12-01

    The genetic defect responsible for Huntington disease was originally localized near the tip of the short arm of chromosome 4 by genetic linkage to the locus D4S10. Several markers closer to Huntington disease have since been isolated, but these all appear to be proximal to the defect. A physical map that extends from the most distal of these loci, D4S90, to the telomere of chromosome 4 was constructed. This map identifies at least two CpG islands as markers for Huntington disease candidate genes and places the most likely location of the Huntington disease defect remarkably close (within 325 kilobases) to the telomere.

  6. picA, a novel plant-inducible locus on the Agrobacterium tumefaciens chromosome.

    PubMed Central

    Rong, L; Karcher, S J; O'Neal, K; Hawes, M C; Yerkes, C D; Jayaswal, R K; Hallberg, C A; Gelvin, S B

    1990-01-01

    We used the transposon Mu dI1681 to identify genes on the Agrobacterium tumefaciens chromosome that are inducible by extracts from carrot roots. One such locus (picA, for plant inducible chromosomal), harbored by A. tumefaciens At156, was inducible 10- to 50-fold by these extracts. Mutation of picA had no detectable effect upon bacterial growth or virulence under laboratory assay conditions. However, A. tumefaciens cells harboring a mutated picA locus aggregated into long "ropes" when incubated with pea root tip cells. Such aggregation was not displayed by the parental strain A. tumefaciens A136. A preliminary characterization of the inducing compound in the carrot root extract suggests that the active substance is an acidic polysaccharide that is most likely derived from the pectic portion of the plant cell wall. Images PMID:2170328

  7. Is there a gene regulating the scute locus on the third chromosome of D. melanogaster?

    PubMed

    Rendel, J M

    1976-07-01

    A section of the third chromosome of D. melanogaster some 25 to 40 centimorgans long including sr was transferred from a wild-type stock selected by Latter for high scutellar bristle number into a scute stock with a large number of scutellar bristles. This segment is shown to have a large effect on the bristle numbers of wild-type flies, to reduce the strength of canalization of the scute phenotype at 4 bristles, to have little, if any, effect on bristle numbers of scute flies with less that 4 bristles but to increase the number of flies with 5 and 6 scutellar bristles in scute stocks that normally have a large number of flies with 4 bristles. It is suggested that this segment in unselected chromosomes contains a gene that regulates bristle number by repressing the scute locus and that Latter has selected a mutant of the regulator which fails to repress the aciton of the scute locus.

  8. 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.

  9. Primary, Nonsyndromic Vesicoureteric Reflux and Its Nephropathy Is Genetically Heterogeneous, with a Locus on Chromosome 1

    PubMed Central

    Feather, Sally A.; Malcolm, Sue; Woolf, Adrian S.; Wright, Victoria; Blaydon, Diana; Reid, Christopher J. D.; Flinter, Frances A.; Proesmans, Willem; Devriendt, Koen; Carter, Joan; Warwicker, Paul; Goodship, Timothy H. J.; Goodship, Judith A.

    2000-01-01

    Primary vesicoureteric reflux (VUR) affects 1%–2% of whites, and reflux nephropathy (RN) causes up to 15% of end-stage renal failure in children and adults. There is a 30–50-fold increased incidence of VUR in first-degree relatives of probands, compared with the general population. We report the results of the first genomewide search of VUR and RN; we studied seven European families whose members exhibit apparently dominant inheritance. We initially typed 387 polymorphic markers spaced, on average, at 10 cM throughout the genome; we used the GENEHUNTER program to provide parametric and nonparametric linkage analyses of affected individuals. The most positive locus spanned 20 cM on 1p13 between GATA176C01 and D1S1653 and had a nonparametric LOD score (NPL) of 5.76 (P=.0002) and a parametric LOD score of 3.16. Saturation with markers at 1-cM intervals increased the NPL to 5.94 (P=.00009). Hence, VUR maps to a locus on chromosome 1. There was evidence of genetic heterogeneity at the chromosome 1 locus, and 12 additional loci were identified genomewide, with P<.05. No significant linkage was found to 6p, where a renal and ureteric malformation locus has been reported, or to PAX2, mutations of which cause VUR in renal-coloboma syndrome. Our results support the hypothesis that VUR is a genetic disorder. PMID:10739767

  10. Locus-specific targeting to the X-chromosome revealed by the RNA interactome of CTCF

    PubMed Central

    Kung, Johnny T.; Kesner, Barry; An, Jee Young; Ahn, Janice Y.; Cifuentes-Rojas, Catherine; Colognori, David; Jeon, Yesu; Szanto, Attila; del Rosario, Brian C.; Pinter, Stefan F.; Erwin, Jennifer A.; Lee, Jeannie T.

    2015-01-01

    CTCF is a master regulator that plays important roles in genome architecture and gene expression. How CTCF is recruited in a locus-specific manner is not fully understood. Evidence from epigenetic processes, such as X-chromosome inactivation (XCI), indicates that CTCF associates functionally with RNA. Using genome-wide approaches to investigate the relationship between its RNA interactome and epigenomic landscape, here we report that CTCF binds thousands of transcripts in mouse embryonic stem cells, many in close proximity to CTCF’s genomic binding sites. CTCF is a specific and high-affinity RNA-binding protein (Kd <1 nM). During XCI, CTCF differentially binds the active and inactive X-chromosomes and interacts directly with Tsix, Xite, and Xist RNAs. Tsix and Xite RNAs target CTCF to the X-inactivation center, thereby inducing homologous X-chromosome pairing. Our work elucidates one mechanism by which CTCF is recruited in a locus-specific manner and implicates CTCF-RNA interactions in long-range chromosomal interactions. PMID:25578877

  11. Sequence analysis of a pea comb locus on chicken chromosome 1.

    PubMed

    Sato, S; Sato, S; Otake, T; Suzuki, C; Uemoto, Y; Saburi, J; Hashimoto, H; Kobayashi, E

    2010-12-01

    To facilitate gene identification, this study aimed to narrow the scope of the genome region affecting chicken comb type by using two bird populations. First, an F2 resource population was generated by crossing Japanese game fowl (Shamo; pea comb, P/p and P/P) with White Plymouth Rock (single comb, p/p). Comb types of the 240 F2 offspring produced by an F1 intercross between eight males and 57 females were segregated at a ratio of 3:1 (pea:single). The pea comb locus was mapped to a chromosomal region on Gallus gallus chromosome 1 that was flanked by microsatellite markers MCW0112, MCW0019 and ABR521. The second population (five-generation, n=1300 animals) was derived from a cross between Shamo and Rhode Island Red (single comb, p/p) that had been genotyped for additional polymorphic single nucleotide polymorphisms and microsatellite markers within this region through development of chicken draft sequences. To close some gaps in these draft sequences, we constructed a bacterial artificial chromosome contig and sequenced it using the shotgun sequencing technique. Chickens selected from pedigrees in these populations were grouped by inheritance of a P or p haplotype at the locus constructed by the additional markers. Finally, this locus was fine-mapped to roughly 60 kb based on the association of haplotypes and comb types. Chicken genome sequences suggest that the most likely polymorphism responsible for the pea comb locus is a duplicated sequence and that the sex determining region Y-box 5 gene, one predicted gene and one expressed sequence tag in a critical region may be associated with the duplicated sequence. PMID:20412124

  12. Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse

    PubMed Central

    Balcova, Maria; Faltusova, Barbora; Gergelits, Vaclav; Bhattacharyya, Tanmoy; Mihola, Ondrej; Trachtulec, Zdenek; Knopf, Corinna; Fotopulosova, Vladana; Chvatalova, Irena; Gregorova, Sona; Forejt, Jiri

    2016-01-01

    Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies. PMID:27104744

  13. Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.

    PubMed

    Balcova, Maria; Faltusova, Barbora; Gergelits, Vaclav; Bhattacharyya, Tanmoy; Mihola, Ondrej; Trachtulec, Zdenek; Knopf, Corinna; Fotopulosova, Vladana; Chvatalova, Irena; Gregorova, Sona; Forejt, Jiri

    2016-04-01

    Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies.

  14. A new locus for arrhythmogenic right ventricular dysplasia on the long arm of chromosome 14

    SciTech Connect

    Severini, G.M.; Krajinovic, M.; Falaschi, A.

    1996-01-15

    Familial arrhythmogenic right ventricular cardiomyopathy or dysplasia (ARVD) is an idiopathic heart muscle disease with an autosomal-dominant pattern of transmission, characterized by fibro-fatty replacement of the right ventricular myocardium and ventricular arrhythmias. Recently, linkage to the chromosome 14q23-q24 (locus D14S42) has been reported in two families. In the present study, three unrelated families with ARVD were investigated. According to strict diagnostic criteria, 13 of 37 members were considered to be affected. Linkage to the D14S42 locus was excluded. On the other hand, linkage was found in the region 14q12-q22 in all three families (cumulative two-point lod score is 3.26 for D14S252), with no recombination between the detected locus and the disease gene. With multipoint linkage analysis, a maximal cumulative lod score of 4.7 was obtained in the region between loci D14S252 and D14S257. These data indicate that a novel gene causing familial ARVD (provisionally named ARVD2) maps to the long arm of chromosome 14, thus supporting the hypothesis of genetic heterogeneity in this disease. 33 refs., 4 figs., 3 tabs.

  15. Integration of genetic and physical maps of the Primula vulgaris S locus and localization by chromosome in situ hybridization.

    PubMed

    Li, Jinhong; Webster, Margaret A; Wright, Jonathan; Cocker, Jonathan M; Smith, Matthew C; Badakshi, Farah; Heslop-Harrison, Pat; Gilmartin, Philip M

    2015-10-01

    Heteromorphic flower development in Primula is controlled by the S locus. The S locus genes, which control anther position, pistil length and pollen size in pin and thrum flowers, have not yet been characterized. We have integrated S-linked genes, marker sequences and mutant phenotypes to create a map of the P. vulgaris S locus region that will facilitate the identification of key S locus genes. We have generated, sequenced and annotated BAC sequences spanning the S locus, and identified its chromosomal location. We have employed a combination of classical genetics and three-point crosses with molecular genetic analysis of recombinants to generate the map. We have characterized this region by Illumina sequencing and bioinformatic analysis, together with chromosome in situ hybridization. We present an integrated genetic and physical map across the P. vulgaris S locus flanked by phenotypic and DNA sequence markers. BAC contigs encompass a 1.5-Mb genomic region with 1 Mb of sequence containing 82 S-linked genes anchored to overlapping BACs. The S locus is located close to the centromere of the largest metacentric chromosome pair. These data will facilitate the identification of the genes that orchestrate heterostyly in Primula and enable evolutionary analyses of the S locus.

  16. A high-resolution map in the chromosomal region surrounding the Lps locus

    SciTech Connect

    Qureshi, S.T.; Lariviere, L.; Gros, P.

    1996-02-01

    The Lps locus on mouse chromosome 4 controls host responsiveness to lipopolysaccharide, a major component of the outer membrane of Gram-negative bacteria. The C3H/HeJ inbred mouse strain is characterized by a mutant Lps allele (Lps{sup d}) that renders it hyporesponsive to LPS and naturally tolerant of its lethal effects. To identify the Lps gene by a positional cloning strategy, we have analyzed a total of 1604 backcross mice from a preexisting interspecific backcross panel of 259 (Mus spretus x C57BL/6J)F1 x C57BL/6J and two novel panels of 597 (DBA/2J x C3H/HeJ)F1 x C3H/HeJ and 748 (C57BL/6J x C3H/HeJ)F1 x C3H/HeJ segregating at Lps. A total of 50 DNA markers have been mapped in a 11.8-cM span overlapping the Lps locus. This positions the Lps locus within a 1.1-cM interval, flanked proximally by a large cluster of markers, including three known genes (Cd30l, Hxb, and Ambp), and distally by two microsatellite markers (D4Mit7/D4Mit178). The localization of the Lps locus is several centimorgans proximal to that previously assigned. 52 refs., 5 figs., 2 tabs.

  17. Polymer models of the hierarchical folding of the Hox-B chromosomal locus

    NASA Astrophysics Data System (ADS)

    Annunziatella, Carlo; Chiariello, Andrea M.; Bianco, Simona; Nicodemi, Mario

    2016-10-01

    As revealed by novel technologies, chromosomes in the nucleus of mammalian cells have a complex spatial organization that serves vital functional purposes. Here we use models from polymer physics to identify the mechanisms that control their three-dimensional spatial organization. In particular, we investigate a model of the Hox-B locus, an important genomic region involved in embryo development, to expose the principles regulating chromatin folding and its complex behaviors in mouse embryonic stem cells. We reconstruct with high accuracy the pairwise contact matrix of the Hox-B locus as derived by Hi-C experiments and investigate its hierarchical folding dynamics. We trace back the observed behaviors to general scaling properties of polymer physics.

  18. A quantitative trait locus on chromosome 6 regulates the onset of puberty in mice.

    PubMed

    Nathan, Brandon M; Hodges, Craig A; Supelak, Pamela J; Burrage, Lindsay C; Nadeau, Joseph H; Palmert, Mark R

    2006-11-01

    Puberty is a fundamental developmental process experienced by all reproductively competent adults, yet the specific factors that regulate variation in its timing remain elusive. Using a new approach to identifying these factors, we have performed a survey among a panel of chromosome substitution strains (for inbred strains C57BL/6J and A/J) followed by linkage analysis to map a quantitative trait locus (QTL) on the distal end of chromosome 6 that regulates pubertal timing (as assessed by vaginal opening) in mice. The location of the QTL was then refined to a region between marker D6MIT59 and the end of the chromosome by generating and phenotyping a panel of 12 congenic strains, each with a unique and overlapping homozygous segment of the A/J chromosome on an otherwise uniform C57BL/6J genomic background. Additional characterization of the QTL indicated that the effects of the responsible gene(s) are gender specific and inherited in a codominant manner without parent-of-origin effects. These findings represent an important advancement toward identification of novel factors that regulate maturation of the hypothalamic-pituitary-gonadal axis and determine the timing of puberty.

  19. Massive Amplification at an Unselected Locus Accompanies Complex Chromosomal Rearrangements in Yeast

    PubMed Central

    Thierry, Agnès; Khanna, Varun; Dujon, Bernard

    2016-01-01

    Gene amplification has been observed in different organisms in response to environmental constraints, such as limited nutrients or exposure to a variety of toxic compounds, conferring them with specific phenotypic adaptations via increased expression levels. However, the presence of multiple gene copies in natural genomes has generally not been found in the absence of specific functional selection. Here, we show that the massive amplification of a chromosomal locus (up to 880 copies per cell) occurs in the absence of any direct selection, and is associated with low-order amplifications of flanking segments in complex chromosomal alterations. These results were obtained from mutants with restored phenotypes that spontaneously appeared from genetically engineered strains of the yeast Saccharomyces cerevisiae suffering from severe fitness reduction. Grossly extended chromosomes (macrotene) were formed, with complex structural alterations but sufficient stability to propagate unchanged over successive generations. Their detailed molecular analysis, including complete genome sequencing, identification of sequence breakpoints, and comparisons between mutants, revealed novel mechanisms causing their formation, whose combined action underlies the astonishing dynamics of eukaryotic chromosomes and their consequences. PMID:26945028

  20. Energy homeostasis targets chromosomal reconfiguration of the human GH1 locus.

    PubMed

    Vakili, Hana; Jin, Yan; Cattini, Peter A

    2014-11-01

    Levels of pituitary growth hormone (GH), a metabolic homeostatic factor with strong lipolytic activity, are decreased in obese individuals. GH declines prior to the onset of weight gain in response to excess caloric intake and hyperinsulinemia; however, the mechanism by which GH is reduced is not clear. We used transgenic mice expressing the human GH (hGH) gene, GH1, to assess the effect of high caloric intake on expression as well as the local chromosome structure of the intact GH1 locus. Animals exposed to 3 days of high caloric intake exhibited hyperinsulinemia without hyperglycemia and a decrease in both hGH synthesis and secretion, but no difference in endogenous production of murine GH. Efficient GH1 expression requires a long-range intrachromosomal interaction between remote enhancer sequences and the proximal promoter region through "looping" of intervening chromatin. High caloric intake disrupted this interaction and decreased both histone H3/H4 hyperacetylation and RNA polymerase II occupancy at the GH1 promoter. Incorporation of physical activity muted the effects of excess caloric intake on insulin levels, GH1 promoter hyperacetylation, chromosomal architecture, and expression. These results indicate that energy homeostasis alters postnatal hGH synthesis through dynamic changes in the 3-dimensional chromatin structure of the GH1 locus, including structures required for cell type specificity during development.

  1. The slick hair coat locus maps to chromosome 20 in Senepol-derived cattle.

    PubMed

    Mariasegaram, M; Chase, C C; Chaparro, J X; Olson, T A; Brenneman, R A; Niedz, R P

    2007-02-01

    The ability to maintain normal temperatures during heat stress is an important attribute for cattle in the subtropics and tropics. Previous studies have shown that Senepol cattle and their crosses with Holstein, Charolais and Angus animals are as heat tolerant as Brahman cattle. This has been attributed to the slick hair coat of Senepol cattle, which is thought to be controlled by a single dominant gene. In this study, a genome scan using a DNA-pooling strategy indicated that the slick locus is most likely on bovine chromosome 20 (BTA20). Interval mapping confirmed the BTA20 assignment and refined the location of the locus. In total, 14 microsatellite markers were individually genotyped in two pedigrees consisting of slick and normal-haired cattle (n = 36), representing both dairy and beef breeds. The maximum LOD score was 9.4 for a 4.4-cM support interval between markers DIK2416 and BM4107. By using additional microsatellite markers in this region, and genotyping in six more pedigrees (n = 86), the slick locus was further localized to the DIK4835 - DIK2930 interval. PMID:17257189

  2. Localization of a locus responsible for the bovine chondrodysplastic dwarfism (bcd) on chromosome 6.

    PubMed

    Yoneda, K; Moritomo, Y; Takami, M; Hirata, S; Kikukawa, Y; Kunieda, T

    1999-06-01

    A hereditary chondrodysplastic dwarfism caused by an autosomal recessive gene has been reported in a population of Japanese Brown cattle. Affected calves show an insufficiency of endochondral ossification at the long bones of the limbs. In the present study, we mapped the locus responsible for the disease (bcd) by linkage analysis, using microsatellite markers and a single paternal half-sib pedigree obtained from commercial herds. Linkage analysis revealed a significant linkage between the bcd locus and marker loci on the distal region of bovine Chromosome (Chr) 6. The bcd locus was mapped in the interval between microsatellite markers BM9257 and BP7 or BMS511 with a recombination fraction of 0.05 and 0.06, and a lod score of 8.6 and 10.1, respectively. A comparison of genetic maps between bovine Chr 6 and human Chr 4 or mouse Chr 5 indicates possible candidate genes including FGFR3 and BMP3 genes, which are responsible for human chondrodysplasias and associated with bone morphogenesis, respectively.

  3. Identification of the LHRH locus in a flow-sorted human chromosome 8 cosmid library

    SciTech Connect

    Bruskiewich, R.; Schertzer, M.; Wood, S.

    1994-09-01

    Genomic sequence for luteinizing hormone releasing hormone (LHRH) gene has been published recently. The LHRH locus has been mapped to 8p21-8p11.2 using tritium labelling for in situ hybridization. Our goal is to determine a more precise localization for for LHRH. We have identified a genomic clone, 37F12, within the LA08NC01 flow-sorted human chromosome 8 cosmid library using PCR amplification of primary and secondary pools of mixed cosmids. The 37F12 cosmid was screened for novel sequence polymorphisms suitable for linkage analysis and preliminary data indicates that 37F12 contains a CA repeat sequence. The possible role of LHRH in human disease phenotypes mapping to 8p is unknown. Currently the only marker reported for LHRH is an RFLP that exhibits 11% heterozygosity. Development of a highly informative PCR marker will facilitate family studies where this locus is being excluded as a candidate locus for a disease phenotype.

  4. A third locus for autosomal dominant cerebellar ataxia Type I maps to chromosome 14q24. 3-qter: Evidence for the existence of a fourth locus

    SciTech Connect

    Stevanin, G.; Guern, E.L.; Ravise, N.; Chneiweiss, H.; Duerr, A.; Cancel, G.; Vignal, A.; Boch, A.L.; Ruberg, M.; Penet, C.; Pothin, Y.; Lagroua, I.; Haguenau, M.; Rancurel, G.; Weissenbach, J.; Agid, Y.; Brice, A.

    1994-01-01

    The autosomal dominant cerebellar ataxias (ADCA) type I are a group of neurological disorders that are clinically and genetically heterogeneous. Two genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are already localized. The authors have mapped a third locus to chromosome 14q24.3-qter, by linkage analysis in a non-SCA1/non-SCA2 family and have confirmed its existence in a second such family. The authors suggest designating this new locus [open quotes]SCA3.[close quotes] Combined analysis of the two families restricted the SCA3 locus to a 15-cM interval between markers D14S67 and D14S81. The gene for Machado-Joseph disease (MJD), a clinically different form of ADCA type I, has been recently assigned to chromosome 14q24.3-q32. Although the SCA3 locus is within the MJD region, linkage analyses cannot yet demonstrate whether they result from mutations of the same gene. Linkage to all three loci (SCA1, SCA2, and SCA3) was excluded in another family, which indicates the existence of a fourth ADCA type I locus. 36 refs., 4 figs., 3 tabs.

  5. A YAC contig encompassing the chromosome 7p locus for autosomal dominant retinitis pigmentosa

    SciTech Connect

    Inglehearn, C.F.; Keen, T.J.; Ratel, R.

    1994-09-01

    Retinitis pigmentosa is an inherited retinal degeneration characterized by night blindness and loss of peripheral vision, often leading to complete blindness. The autosomal dominant form (adRP) maps to at least six different loci, including the rhodopsin and peripherin/Rds genes and four loci identified only by linkage analysis on chromosomes 7p, 7q, 8cen and 19q. The 7p locus was reported by this laboratory in a large English family, with a lod score of 16.5. Several new genetic markers have been tested in the family and this locus has now been refined to an interval of approximately 1 cM between markers D7S795 and D7S484 in the 7p13-15 region. In order to clone the gene for adRP, we have used microsatellites and STSs from the region to identify over 80 YACs, from four different libraries, which map to this interval. End clones from key YACs were isolated for the generation of additional STSs. Eleven microsatellite markers between D7S435 (distal) and D7S484 (proximal) have been ordered by a combination of both physical and genetic mapping. In this way we have now obtained a YAC contig spanning approximately 3 megabases of chromosome 7p within which the adRP gene must lie. One gene (aquaporin) and one chromosome 7 brain EST have been placed on the contig but both map distal to the region of interest. Sixteen other ESTs and three further known 7p genes mapping in the region have been excluded. We are now attempting to build a cosmid contig in the defined interval and identify further expressed sequences from both YACs and cosmids to test as candidates for the adRP gene.

  6. Profound parental bias associated with chromosome 14 acquired uniparental disomy indicates targeting of an imprinted locus.

    PubMed

    Chase, A; Leung, W; Tapper, W; Jones, A V; Knoops, L; Rasi, C; Forsberg, L A; Guglielmelli, P; Zoi, K; Hall, V; Chiecchio, L; Eder-Azanza, L; Bryant, C; Lannfelt, L; Docherty, L; White, H E; Score, J; Mackay, D J G; Vannucchi, A M; Dumanski, J P; Cross, N C P

    2015-10-01

    Acquired uniparental disomy (aUPD) is a common finding in myeloid malignancies and typically acts to convert a somatically acquired heterozygous mutation to homozygosity. We sought to identify the target of chromosome 14 aUPD (aUPD14), a recurrent abnormality in myeloid neoplasms and population cohorts of elderly individuals. We identified 29 cases with aUPD14q that defined a minimal affected region (MAR) of 11.2 Mb running from 14q32.12 to the telomere. Exome sequencing (n=7) did not identify recurrently mutated genes, but methylation-specific PCR at the imprinted MEG3-DLK1 locus located within the MAR demonstrated loss of maternal chromosome 14 and gain of paternal chromosome 14 (P<0.0001), with the degree of methylation imbalance correlating with the level of aUPD (r=0.76; P=0.0001). The absence of driver gene mutations in the exomes of three individuals with aUPD14q but no known haematological disorder suggests that aUPD14q may be sufficient to drive clonal haemopoiesis. Analysis of cases with both aUPD14q and JAK2 V617F (n=11) indicated that aUPD14q may be an early event in some cases but a late event in others. We conclude that aUPD14q is a recurrent abnormality that targets an imprinted locus and may promote clonal haemopoiesis either as an initiating event or as a secondary change. PMID:26114957

  7. The osteoporosis-pseudoglioma syndrome locus is on chromosome 11q

    SciTech Connect

    Gong, Y.; Vikkula, M.; Boon, L.M.

    1994-09-01

    The osteoporosis-pseudoglioma syndrome (OPS), is a rare autosomal recessive disorder characterized by severe osteoporosis with multiple fractures and blindness, both occurring in childhood. The precise pathogenic mechanism for OPS is unknown. Insights into its cause may be useful towards understanding the pathophysiology of more common disorders, such as senile osteoporosis, persistent hyperplasia of the primary vitreous, and retinopathy of prematurity, whose features have some similarity with OPS. As a first step in determining the cause of OPS, we have mapped the locus of the disorder to chromosome 11q. This was accomplished by assuming genetic homogeneity and by performing linkage analysis with homozygosity mapping in 18 individuals (7 patients, 5 unaffected siblings, and 7 parents) from 3 different consanguineous kindreds. Since the condition could be caused by an abnormal extracellular matrix component, we began by testing several candidate genes (e.g., COL1A1, COL1A2, Osteopontin, Osteonectin) distributed on 12 different chromosomes. We also initiated a systematic search at 20 cM intervals with highly polymorphic simple sequence tandem repeats. Linkage and homozygosity was detected with marker D11S913 (LOD score 3.8 at {theta} = 0). Additional markers are being tested to confirm this observation. The fibroblast collagenase, fibronectin-like-2 gene and rod outer segment protein-1 (ROM 1) also map to chromosome 11q and are candidate genes.

  8. Localization of a novel natural killer triggering receptor locus to human chromosome 3p23-p21 and mouse chromosome 9

    SciTech Connect

    Young, H.A.; Jenkins, N.A.; Copeland, N.G.; Simek, S.; Lerman, M.I.; Zbar, B.; Glenn, G.; Ortaldo, J.R.; Anderson, S.K.

    1993-05-01

    A novel gene (NKTR) that is involved in the recognition of tumor cells by large granular lymphocytes (LGLs) has been assigned to the short arm of human chromosome 3 in the region 3p23-p21 by somatic cell hybrid analysis. Interspecific backcross analysis revealed that the murine homologue maps to the distal end of mouse chromosome 9 and is closely linked to the locus coding for cholecystokinin (Cck). This region of mouse 9 shares a region of homology with human 3p. Thus, the placement of NKTR in these regions confirms and extends the relationship between these human and mouse chromosomes. 11 refs., 2 figs.

  9. The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis

    PubMed Central

    Jones, Kevin B.; Barrott, Jared J.; Xie, Mingchao; Haldar, Malay; Jin, Huifeng; Zhu, Ju-Fen; Monument, Michael J.; Mosbruger, Tim L.; Langer, Ellen M.; Randall, R. Lor; Wilson, Richard K.; Cairns, Bradley R.; Ding, Li; Capecchi, Mario R.

    2016-01-01

    Synovial sarcomas are aggressive soft-tissue malignancies that express chromosomal translocation-generated fusion genes, SS18-SSX1 or SS18-SSX2 in most cases. Here, we report a mouse sarcoma model expressing SS18-SSX1, complementing our prior model expressing SS18-SSX2. Exome sequencing identified no recurrent secondary mutations in tumors of either genotype. Most of the few mutations identified in single tumors were present in genes that were minimally or not expressed in any of the tumors. Chromosome 6, either entirely or around the fusion gene expression locus, demonstrated a copy number gain in a majority of tumors of both genotypes. Thus, by fusion oncogene coding sequence alone, SS18-SSX1 and SS18-SSX2 can each drive comparable synovial sarcomagenesis, independent from other genetic drivers. SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences overall. In direct tumorigenesis comparisons, SS18-SSX2 was slightly more sarcomagenic than SS18-SSX1, but equivalent in its generation of biphasic histologic features. Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. This suggests that the translocated locus may drive genotype-phenotype differences more than the coding sequence of the fusion gene created. Two possible roles for native SSX2 in synovial sarcomagenesis are explored. Thus even specific partial failures of mouse genetic modeling can be instructive to human tumor biology. PMID:26947017

  10. A genomewide screen for chronic rhinosinusitis genes identifies a locus on chromosome 7q

    PubMed Central

    Pinto, Jayant M.; Hayes, M. Geoffrey; Schneider, Daniel; Naclerio, Robert M.; Ober, Carole

    2014-01-01

    Background Chronic rhinosinusitis is an important public health problem with substantial impact on patient quality of life and health care costs. We hypothesized that genetic variation may be one factor that affects this disease. Objective To identify genetic variation underlying susceptibility to chronic rhinosinusitis using a genome-wide approach. Methods We studied a religious isolate that practices a communal lifestyle and shares common environmental exposures. Using physical examination, medical interviews, and a review of medical records, we identified 8 individuals with chronic rhinosinusitis out of 291 screened. These 8 individuals were related to each other in a single 60 member, 9 generation pedigree. A genome-wide screen for loci influencing susceptibility to chronic rhinosinusitis using 1123 genome-wide markers was conducted. Results The largest linkage peak (P = 0.0023; 127.15 cM, equivalent to LOD=2.01) was on chromosome 7q31.1-7q32.1, 7q31 (127.15 cM; 1-LOD support region: 115cM to 135cM) and included the CFTR locus. Genotyping of 38 mutations in the CFTR gene did not reveal variation accounting for this linkage signal. Conclusion Understanding the genes involved in chronic rhinosinusitis may lead to improvements in its diagnosis and treatment. Our results represent the first genome-wide screen for chronic rhinosinusitis and suggest that a locus on 7q31.1-7q32.1 influences disease susceptibility. This may be the CFTR gene or another nearby locus. PMID:18622306

  11. Positional cloning of the chromosome 14 Alzheimer`s disease locus

    SciTech Connect

    Clark, R.F.; Korenblat, K.M.; Goate, A.M.

    1994-09-01

    Genetic linkage analysis had indicated a locus for familial early-onset Alzheimer`s disease (FAD) on chromosome 14 at q24.3. The FAD locus has been shown previously to lie between the dinucleotide markers D14S61 and D14S63, a genetic distance of approximately 13 cM. We are currently attempting to identify the gene using a positional cloning strategy. The first step towards the isolation and characterization of this locus was the construction of an overlapping YAC contig covering the entire region. Over forty YACs which map to this region have been isolated from the St. Louis and CEPH libraries by a combination of YAC end sequence walking and sequence tagged site mapping. Our contig fully spans the complete domain, encompassing all genetic markers non-recombinant with FAD (i.e. D14S76, D14S43, D14S71, D14S77) and the two nearest flanking FAD-recombinant markers. With restriction mapping of the domain, we can determine the exact size of the region. As a second step, the YACs in this contig are currently being inspected for expressed sequences by exon trapping, initially on those YACs known to be nonchimeric. We have currently made exon-trapped libraries from YACs that have the markers D14S76 and D14S43. Sequence analysis of these libraries indicates that a trapped exon is identified on average for each 30 kb of YAC DNA. The trapped exons are being screened to identify likely candidate genes, which will be examined for mutations in FAD families.

  12. 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.

  13. Distribution of Unlinked Transpositions of a Ds Element from a T-DNA Locus on Tomato Chromosome 4

    PubMed Central

    Briza, J.; Carroll, B. J.; Klimyuk, V. I.; Thomas, C. M.; Jones, D. A.; Jones, JDG.

    1995-01-01

    In maize, receptor sites for unlinked transpositions of Activator (Ac) elements are not distributed randomly. To test whether the same is true in tomato, the receptor sites for a Dissociation (Ds) element derived from Ac, were mapped for 26 transpositions unlinked to a donor T-DNA locus on chromosome 4. Four independent transposed Dss mapped to sites on chromosome 4 genetically unlinked to the donor T-DNA, consistent with a preference for transposition to unlinked sites on the same chromosome as opposed to sites on other chromosomes. There was little preference among the nondonor chromosomes, except perhaps for chromosome 2, which carried seven transposed Dss, but these could not be proven to be independent. However, these data, when combined with those from other studies in tomato examining the distribution of transposed Acs or Dss among nondonor chromosomes, suggest there may be absolute preferences for transposition irrespective of the chromosomal location of the donor site. If true, transposition to nondonor chromosomes in tomato would differ from that in maize, where the preference seems to be determined by the spatial arrangement of chromosomes in the interphase nucleus. The tomato lines carrying Ds elements at known locations are available for targeted transposon tagging experiments. PMID:8536985

  14. Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.

    PubMed

    Schumacher, Fredrick R; Wang, Zhaoming; Skotheim, Rolf I; Koster, Roelof; Chung, Charles C; Hildebrandt, Michelle A T; Kratz, Christian P; Bakken, Anne C; Bishop, D Timothy; Cook, Michael B; Erickson, R Loren; Fosså, Sophie D; Greene, Mark H; Jacobs, Kevin B; Kanetsky, Peter A; Kolonel, Laurence N; Loud, Jennifer T; Korde, Larissa A; Le Marchand, Loic; Lewinger, Juan Pablo; Lothe, Ragnhild A; Pike, Malcolm C; Rahman, Nazneen; Rubertone, Mark V; Schwartz, Stephen M; Siegmund, Kimberly D; Skinner, Eila C; Turnbull, Clare; Van Den Berg, David J; Wu, Xifeng; Yeager, Meredith; Nathanson, Katherine L; Chanock, Stephen J; Cortessis, Victoria K; McGlynn, Katherine A

    2013-07-01

    Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk. PMID:23462292

  15. A curly-tail modifier locus, mct1, on mouse chromosome 17

    SciTech Connect

    Letts, V.A.; Schork, N.J.; Frankel, W.N.

    1995-10-10

    The major gene for neural tube defects, ct, in the curly-tail (CT) mouse strain was mapped previously to mouse chromosome 4 by combining linkage data from several backcrosses. The penetrance of the neural tube trait, already incomplete in the CT strain, was further reduced in several of these backcrosses, suggesting the existence of recessive modifiers or strain-specific susceptibility alleles. Here we describe the mapping of a curly-tail modifier locus, mct1, to chromosome 17 in moderate and low penetrance crosses of CT with BALB/cByJ and Mus spretus. No effect of mct1 was seen in a higher penetrance cross with the BXD-8/Ty strain, confirming that ct is the major gene in the model. Homozygosity at both ct and mct1 loci was sufficient to account for all of the affected individuals in the BALB/cByJ cross and most of the affected individuals in the M. spretus cross and was the preferred model overall. No evidence was found for epistatic interaction between ct and mct1. 30 refs., 2 figs., 3 tabs.

  16. The genetic locus for free sialic acid storage disease maps to the long arm of chromosome 6

    SciTech Connect

    Haataja, L.; Schleutker, J.; Laine, A.P.; Savontaus, M.L.; Aula, P. ); Renlund, M. ); Dib, C.; Weissenbach, J. ); Peltonen, L. )

    1994-06-01

    Salla disease (SD), or adult-type free sialic acid storage disease, is an autosomal recessive lysosomal storage disorder characterized by impaired transport of free sialic acid across the lysosomal membrane and severe psychomotor retardation. Random linkage analysis of a sample of 27 Finnish families allowed localization of the SD locus to the long arm of chromosome 6. The highest lod score of 8.95 was obtained with a microsatellite marker of locus D6S286 at [theta] - .00. Evidence for linkage disequilibrium was observed between the SD locus and the alleles of three closely linked markers, suggesting that the length of the critical region for the SD locus is in the order of 190 kb. 35 refs., 3 figs., 2 tabs.

  17. Linkage of Thomsen disease to the T-cell-receptor beta (TCRB) locus on chromosome 7q35

    SciTech Connect

    Abdalla, J.A.; Casley, W.L.; Cousin, H.K.; Hudson, A.J.; Hashimoto, L.; Ebers, G.C. ); Murphy, E.G. ); Cornelis, F.C. )

    1992-09-01

    The chromosomal localization of the gene for Thomsen disease, an autosomal dominant form of myotonia congenita, is unknown. Electrophysiologic data in Thomsen disease point to defects in muscle-membrane ion-channel function. A mouse model of myotonia congenita appears to result from transposon inactivation of a muscle chloride-channel gene which maps to a region of mouse chromosome 6. The linkage group containing this gene includes several loci which have human homologues on human chromosome 7q31-35 (synteny), and this is a candidate region for the Thomsen disease locus. Linkage analysis of Thomsen disease to the T-cell-receptor beta (TCRB) locus at 7q35 was carried out in four pedigrees (25 affected and 23 unaffected individuals) by using a PCR-based dinucleotide repeat polymorphism in the TCRB gene. Two-point linkage analysis between Thomsen disease and TCRB showed a maximum cumulative lod score of 3.963 at a recombination fraction of .10 (1-lod support interval .048-.275). The authors conclude that the Thomsen disease locus is linked to the TCRB locus in these families. 30 refs., 6 figs., 1 tab.

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

    SciTech Connect

    Nikali, K.; Suomalainen, A.; Koskinen, T.; Peltonen, L.; Terwilliger, J.; Weissenbach, J.

    1995-05-01

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

  19. Tightly linked flanking microsatellite markers for the Usher syndrome type I locus on the short arm of chromosome 11

    SciTech Connect

    Keats, B.J.B.; Nouri, N.; Pelias, M.Z.; Deininger, P.L. ); Litt, M. )

    1994-04-01

    Usher syndrome type I is an autosomal recessive disease characterized by profound congenital hearing impairment and vestibular dysfunction followed by the onset of progressive pigmentary retinopathy in childhood or early adolescence. A locus (USH1C) for one form of this disease was previously assigned to the short arm of chromosome 11 through linkage studies in the Acadian population of southwestern Louisiana. Linkage analyses of a set of microsatellite markers in 27 Acadian families provide evidence that USH1C lies between D11S861 and D11S928. Three markers (D11S419, D11S921, and D11S899) that lie between the flanking markers show no recombination with USH1C, and all 54 chromosomes with the abnormal allele at the disease locus have identical alleles for D11S419 and D11S921. This haplotype was found on only 10 of 50 chromosomes with the normal allele at the disease locus, suggesting a strong founder effect. Of the 54 chromosomes with the abnormal allele, 12 had a divergent allele at D11S899. These results suggest that USH1C is in the 2-3-cM interval between D11S861 and D11S899. 16 refs., 2 figs., 3 tabs.

  20. Juvenile myoclonic epilepsy in chromosome 6p12-p11: Locus heterogeneity and recombinations

    SciTech Connect

    Liu, A.W.; Delgado-Escueta, A.V.; Serratosa, J.M.

    1996-06-14

    We recently analyzed under homogeneity a large pedigree from Belize with classic juvenile myoclonic epilepsy (JME). After a genome-wide search with 146 microsatellites, we obtained significant linkage between chromosome 6p markers, D6S257 and D6S272, and both convulsive and EEG traits of JME. Recombinations in two affected members defined a 40 cM JME region flanked by D6S313 and D6S258. In the present communication, we explored if the same chromosome 6p11 microsatellites also have a role in JME mixed with pyknoleptic absences. We allowed for heterogeneity during linkage analyses. We tested for heterogeneity by the admixture test and looked for more recombinations. D6S272, D6S466, D6S294, and D6S257 were significantly linked (Z{sub max} > 3.5) to the clinical and EEG traits of 22 families, assuming autosomal dominant inheritance with 70% penetrance. Pairwise Z{sub max} were 4.230 for D6S294 ({theta}{sub m=f} at 0.133) and 4.442 for D6S466 ({theta}{sub m=f} at 0.111). Admixture test (H{sub 2} vs. H{sub 1}) was significant (P = 0.0234 for D6S294 and 0.0128 for D6S272) supporting the hypotheses of linkage with heterogeneity. Estimated proportion of linked families, {alpha}, was 0.50 (95% confidence interval 0.05-0.99) for D6S294 and D6S272. Multipoint analyses and recombinations in three new families narrowed the JME locus to a 7 cM interval flanked by D6S272 and D6S257. 44 refs., 3 figs., 4 tabs.

  1. Mapping of the locus for congenital nephrotic syndrome of the Finnish type (CNF) on chromosome 19

    SciTech Connect

    Kestilae, M.; Maennikkoe, M.; Tryggvason, K.

    1994-09-01

    Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease which forms a distinct entity among congenital nephrotic syndromes. It is characterized by massive proteinuria starting already in utero, large placenta and manifestation of nephrosis soon after birth. The incidence in Finland is about 1 in 8000 newborns, and the disease has been reported occasionally in other countries, particularly in Minnesota, USA. The gene defect in CNF is unknown, but the gene product is likely to be important for kidney development of glomerular filtration. We have used a random mapping approach in 17 Finnish CNF families resulting in the localization of the gene to chromosome 19q12-q13.1. Based on observed recombination events, the CNF locus is flanked by markers D19S191 and D19S224 corresponding to a region under 1 Mb in physical length. Cosmid contigs have been isolated from this region and at least two new polymorphic CA-repeat markers (MKMM1, MKMM2) have been identified from those clones. Statistically highly significant linkage disequilibrium can be observed with markers MKMM1, D19S224 and D19S220, the allelic association being about 65%. The most common haplotype, which was combined from these markers, is found in 60% of chromosomes carrying the CNF mutation. This work has enabled DNA-based diagnosis of CNF, and recently linkage and linkage disequilibrium analyses were used in prenatal diagnostics in a family with one affected child and two healthy siblings. DNA isolated from chorion villus biopsy was analyzed using markers D19S191, MKMM1, D19S224 and D19S220, and the fetus was shown to have the same genotype as the affected child.

  2. Differentiation between homoeologous chromosomes 1A of wheat and 1Am of Triticum monococcum and its recognition by the wheat Ph1 locus.

    PubMed Central

    Dubcovsky, J; Luo, M; Dvorak, J

    1995-01-01

    In most allopolyploid plants, only homogenetic chromosome pairing occurs in meiosis, as a result of the recognition of genome differentiation by the genetic system regulating meiotic chromosome pairing. The nature of differentiation between chromosomes of closely related genomes is examined here by investigating recombination between wheat chromosome 1A and the closely related homoeologous chromosome 1Am of Triticum monococcum. The recognition of the differentiation between these chromosomes by the Ph1 locus, which prevents heterogenetic chromosome pairing in wheat, is also investigated. Chromosomes 1A and 1Am are shown to be colinear, and it is concluded that they are differentiated "substructurally." This substructural differentiation is argued to be recognized by the Ph1 locus. In the absence of Ph1, the distribution and frequencies of crossing over between the 1A and 1Am homoeologues were similar to the distribution and frequencies of crossing over between 1A homologues. The cytogenetic and evolutionary significance of these findings is discussed. PMID:11607556

  3. A locus regulating total serum IgE maps to chromosome 5q

    SciTech Connect

    Amelung, P.J.; Panhuysen, C.I.M.; Postma, D.S. |

    1994-09-01

    Familial aggregation of allergy has been demonstrated in numerous past studies. However, allergy is a complex disorder which is not inherited as a simple Mendelian trait. Total serum IgE levels correlate with the clinical expression of allergy and asthma and can be utilized as a quantitative measure of the allergic phenotype. We studied 92 families from Northern Holland ascertained through a parent with asthma who were originally studied between 1962-1970. Since there is a large number of candidate genes on chromosome 5q, families were genotyped for markers in this region. These genes either directly or indirectly regulate IgE production and the activation and proliferation of cellular elements that are involved in inflammation associated with allergy and asthma. They include IL-4, IL-3, IL-5, IL-9, IL-12, IL-13 and GM-CSF. Segregation analyses revealed recessive inheritance of `high` levels with a mean for the `low` phenotype of 1.51 (32 IU) and 2.52 (331 IU) for the `high` phenotype. Linkage of log IgE with markers on 5q was tested using the sib-pair and the LOD score methods with the genetic model obtained from the segregation analyses. These results provide evidence for a locus controlling IgE levels near the cytokine gene cluster on 5q. This region appears critical in susceptibility to allergy and asthma.

  4. NcoI RFLP at the creatine kinase-muscle type gene locus (CKMM, chromosome 19)

    SciTech Connect

    Coerwinkel-Driessen, M.; Schepens, J.; van Zandvoort, P.; van Oost, B.; Mariman, E.; Wieringa, B. )

    1988-09-12

    A 3.2 kbp human genomic DNA fragment (BamHI-Sau3A) of the 3{prime} untranslated and 3{prime} flanking region of the CKMM gene was isolated and subcloned into the BamHI site of vector pSP64. The CKMM 3{prime}-probe identifies a 2-allele polymorphism with bands at 2.3 and 1.0 kbp (allele A) and 3.3 kbp (allele B). In addition a weak constant 4.2 kbp band is observed. This probe also detects a 2-allele TaqI RFLP reported previously, as either a 4.3 kbp (A) or a 4.2 kbp (B) band. The CKMM locus previously has been assigned to 19q13.2-q13.3. By Southern blot analysis of human-rodent somatic cell hybrids containing unique subregional fragments of chromosome 19 of man the authors have assigned the gene to 19q13.2. Co-dominant segregation was observed in 8 families with 3 generations.

  5. Fine localization of the locus for autosomal dominant retinitis pigmentosa on chromosome 17p

    SciTech Connect

    Goliath, R.; Janssens, P.; Beighton, P.

    1995-10-01

    The term {open_quotes}retintis pigmentosa{close_quotes} (RP) refers to a group of inherited retinal degenerative disorders. Clinical manifestations include night-blindness, with variable age of onset, followed by constriction of the visual field that may progress to total loss of sight in later life. Previous studies have shown that RP is caused by mutations within different genes and may be inherited as an X-linked recessive (XLRRP), autosomal recessive (ARRP), or autosomal dominant (ADRP) trait. The AD form of this group of conditions has been found to be caused by mutations within the rhodopsin gene in some families and the peripherin/RDS gene in others. In addition, some ADRP families have been found to be linked to anonymous markers on 8cen, 7p, 7q,19q, and, more recently, 17p. The ADRP gene locus on the short arm of chromosome 17 was identified in a large South African family (ADRP-SA) of British origin. The phenotypic expression of the disorder, which has been described elsewhere is consistent in the pedigree with an early onset of disease symptoms. In all affected subjects in the family, onset of symptoms commenced before the age of 10 years. 16 refs., 3 figs., 1 tab.

  6. Familial Hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3.

    PubMed Central

    MacRae, C A; Ghaisas, N; Kass, S; Donnelly, S; Basson, C T; Watkins, H C; Anan, R; Thierfelder, L H; McGarry, K; Rowland, E

    1995-01-01

    We have mapped a disease locus for Wolff-Parkinson-White syndrome (WPW) and familial hypertrophic cardiomyopathy (FHC) segregating in a large kindred to chromosome 7 band q3. Although WPW syndrome and FHC have been observed in members of the same family in prior studies, the relationship between these two diseases has remained enigmatic. A large family with 25 surviving individuals who are affected by one or both of these conditions was studied. The disease locus is closely linked to loci D7S688, D7S505, and D7S483 (maximum two point LOD score at D7S505 was 7.80 at theta = 0). While four different FHC loci have been described this is the first locus that can be mutated to cause both WPW and/or FHC. PMID:7657794

  7. Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1.

    PubMed Central

    German, J; Roe, A M; Leppert, M F; Ellis, N A

    1994-01-01

    By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous, far more often than expected (P < 0.0001 by chi 2). Therefore, BLM, the gene that when mutated gives rise to Bloom syndrome, is tightly linked to FES, a gene whose chromosome position is known to be 15q26.1. This successful approach to the assignment of the Bloom syndrome locus to one short segment of the human genome simultaneously (i) demonstrates the power of homozygosity mapping and (ii) becomes the first step in a "reverse" genetics definition of the primary defect in Bloom syndrome. Images PMID:8022833

  8. Bloom syndrome: An analysis of consanguineous families assigns the locus mutated to chromosome band 15q26. 1

    SciTech Connect

    German, J.; Roe, A.M.; Ellis, N.A. ); Leppert, M.F. )

    1994-07-05

    By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous far more often than expected (P < 0.0001 by x[sup 2]). Therefore, BLM, the gene that when mutated gives rise to Bloom syndrome, is tightly linked to FES, a gene whose chromosome position is known to be 15q26.1. This successful approach to the assignment of the Bloom syndrome locus to one short segment of the human genome simultaneously (i) demonstrates the power of homozygosity mapping and (ii) becomes the first step in a [open quotes]reverse[close quotes] genetics definition of the primary defect in Bloom syndrome.

  9. Chromatin Insulator Elements Block Transgene Silencing in Engineered Human Embryonic Stem Cell Lines at a Defined Chromosome 13 Locus

    PubMed Central

    MacArthur, Chad C.; Xue, Haipeng; Van Hoof, Dennis; Lieu, Pauline T.; Dudas, Miroslav; Fontes, Andrew; Swistowski, Andrzej; Touboul, Thomas; Seerke, Rina; Laurent, Louise C.; Loring, Jeanne F.; German, Michael S.; Zeng, Xianmin; Rao, Mahendra S.; Lakshmipathy, Uma; Chesnut, Jonathan D.

    2012-01-01

    Lineage reporters of human embryonic stem cell (hESC) lines are useful for differentiation studies and drug screening. Previously, we created reporter lines driven by an elongation factor 1 alpha (EF1α) promoter at a chromosome 13q32.3 locus in the hESC line WA09 and an abnormal hESC line BG01V in a site-specific manner. Expression of reporters in these lines was maintained in long-term culture at undifferentiated state. However, when these cells were differentiated into specific lineages, reduction in reporter expression was observed, indicating transgene silencing. To develop an efficient and reliable genetic engineering strategy in hESCs, we used chromatin insulator elements to flank single-copy transgenes and integrated the combined expression constructs via PhiC31/R4 integrase-mediated recombination technology to the chromosome 13 locus precisely. Two copies of cHS4 double-insulator sequences were placed adjacent to both 5′ and 3′ of the promoter reporter constructs. The green fluorescent protein (GFP) gene was driven by EF1α or CMV early enhancer/chicken β actin (CAG) promoter. In the engineered hESC lines, for both insulated CAG-GFP and EF1α-GFP, constitutive expression at the chromosome 13 locus was maintained during prolonged culture and in directed differentiation assays toward diverse types of neurons, pancreatic endoderm, and mesodermal progeny. In particular, described here is the first normal hESC fluorescent reporter line that robustly expresses GFP in both the undifferentiated state and throughout dopaminergic lineage differentiation. The dual strategy of utilizing insulator sequences and integration at the constitutive chromosome 13 locus ensures appropriate transgene expression. This is a valuable tool for lineage development study, gain- and loss-of-function experiments, and human disease modeling using hESCs. PMID:21699412

  10. Association between prostate cancer in black Americans and an allele of the PADPRP pseudogene locus on chromosome 13

    SciTech Connect

    Doll, J.A.; Suarez, B.K.; Donis-Keller, H.

    1996-02-01

    Black American men have a higher incidence of cancer of the prostate (CAP), multiple myeloma, and lung cancer than do white American men. The basis for these differences no doubt includes environmental influences, because American blacks have also been found to have a higher incidence of CAP than do African blacks. However, genetic factors may play a role as well. For example, Lyn et al. reported an increase in the frequency of an allele of the poly(ADP-ribose) polymerase (PADPRP) pseudogene locus on chromosome 13 in black Americans with CAP, suggesting the presence of a disease-susceptibility locus. Since only nine CAP patients were studied, proof of the significance of the finding for the general population of black Americans will rely on independent replication of the result and studies with larger sample sizes. We have doubled the number of black American CAP patients studied at the PADPRP pseudogene locus on chromosome 13 and compared them with white Americans with CAP, along with reference samples. In addition, we have determined allele frequencies by using a larger number of white individuals, from the CEPH reference pedigree resource, and a larger number of black Americans than previously reported, which may reflect more accurately the allele frequencies in these populations. We also find a statistically significant association between an allele at the PADPRP pseudogene locus and CAP in black Americans; however, it is not the same allele reported by Lyn et al. Furthermore, we tested CAP tumor DNA for chromosome 13 PADPRP pseudogene region deletions. In contrast to the report of Bhatia et al., we found no evidence for deletions that would suggest the presence of a tumor-suppressor gene in this region of chromosome 13. 16 refs., 2 tabs.

  11. Fine mapping of the diabetes-susceptibility locus, IDDM4, on chromosome 11q13.

    PubMed

    Nakagawa, Y; Kawaguchi, Y; Twells, R C; Muxworthy, C; Hunter, K M; Wilson, A; Merriman, M E; Cox, R D; Merriman, T; Cucca, F; McKinney, P A; Shield, J P; Tuomilehto, J; Tuomilehto-Wolf, E; Ionesco-Tirgoviste, C; Nisticò, L; Buzzetti, R; Pozzilli, P; Joner, G; Thorsby, E; Undlien, D E; Pociot, F; Nerup, J; Rönningen, K S; Bain, S C; Todd, J A

    1998-08-01

    Genomewide linkage studies of type 1 diabetes (or insulin-dependent diabetes mellitus [IDDM]) indicate that several unlinked susceptibility loci can explain the clustering of the disease in families. One such locus has been mapped to chromosome 11q13 (IDDM4). In the present report we have analyzed 707 affected sib pairs, obtaining a peak multipoint maximum LOD score (MLS) of 2.7 (lambda(s)=1.09) with linkage (MLS>=0.7) extending over a 15-cM region. The problem is, therefore, to fine map the locus to permit structural analysis of positional candidate genes. In a two-stage approach, we first scanned the 15-cM linked region for increased or decreased transmission, from heterozygous parents to affected siblings in 340 families, of the three most common alleles of each of 12 microsatellite loci. One of the 36 alleles showed decreased transmission (50% expected, 45.1% observed [P=.02, corrected P=.72]) at marker D11S1917. Analysis of an additional 1,702 families provided further support for negative transmission (48%) of D11S1917 allele 3 to affected offspring and positive transmission (55%) to unaffected siblings (test of heterogeneity P=3x10-4, corrected P=. 01]). A second polymorphic marker, H0570polyA, was isolated from a cosmid clone containing D11S1917, and genotyping of 2,042 families revealed strong linkage disequilibrium between the two markers (15 kb apart), with a specific haplotype, D11S1917*03-H0570polyA*02, showing decreased transmission (46.4%) to affected offspring and increased transmission (56.6%) to unaffected siblings (test of heterogeneity P=1.5x10-6, corrected P=4.3x10-4). These results not only provide sufficient justification for analysis of the gene content of the D11S1917 region for positional candidates but also show that, in the mapping of genes for common multifactorial diseases, analysis of both affected and unaffected siblings is of value and that both predisposing and nonpredisposing alleles should be anticipated.

  12. Towards positional cloning of the locus for benign neonatal epilepsy (EBN1) on chromosome 20

    SciTech Connect

    Schubert, S.; Laccone, F.; Hansmann, I.

    1994-09-01

    Benign neonatal epilepsy is characterized by tonic-clonic and generalized convulsions appearing during the neonatal period and clearing most often by the age of 2 years. EBN, a rare example of primary epilepsy, follows an autosomal dominant mode of inheritance with high penetrance. One locus for EBN (EBN1) was assigned by linkage analysis to the distal 20q segment in proximity to D20S19 and D20S20. The association of 20q sequences with seizures is also underlined by the observation that all 10 probands known with a ring 20 disclose seizures. For positional cloning of the respective locus at 20q13.3, we characterized segmental monosomy in two probands with r(20) and in one proband with a translocation t(10q;20q). The latter proband has a dicentric chromosome 10;20 with breakpoints very distally at 10q and 20q, and seizures similar to those in EBN. Segmental monosomy was investigated by FISH, Southerns and PCR for microsatellites assuming that the respective phenotype, i.e. seizures, is due to loss of 20q sequences (loss of gene function). Probes were used for D20S19, D20S20, D20S24, D20S26, D20S64, D20S102, D20S171, DS20S173, cos23D11, cos35, cos54, as well as for the genes CHRNA4, EDN3, GNAS1, KCNB1, MC3. All of these genes are reasonable candidates for EBN1, due to their function and/or expression pattern. Segmental monosomy for the distal 20q segment was disclosed in the proband with dic(10q;20q) for all loci distal from the critical marker D20S20 and including one of the above genes. In none of the two r(20) probands was any of the distal 20q-markers was found to be deleted, however. It is assumed that seizures with these probands should result from other mechanisms, e.g., by an altered function of respective genes resulting from ring formation. The gene deleted in our proband with dic(10q;20q) is a first candidate gene for EBN1 and is being investigated with respect to its significance for disease manifestation in EBN1.

  13. Genetic and molecular analyses of picA, a plant-inducible locus on the Agrobacterium tumefaciens chromosome.

    PubMed Central

    Rong, L J; Karcher, S J; Gelvin, S B

    1991-01-01

    picA is an Agrobacterium tumefaciens chromosomal locus, identified by Mu d11681 mutagenesis, that is inducible by certain acidic polysaccharides found in carrot root extract. Cloning and genetic analysis of a picA::lacZ fusion defined a region of the picA promoter that is responsible for the induction of this locus. Furthermore, we identified a possible negative regulator of picA expression upstream of the picA locus. This sequence, denoted pgl, has extensive homology to polygalacturonase genes from several organisms and inhibited the induction of the picA promoter when present in multiple copies in A. tumefaciens. DNA sequence analysis indicated at least two long open reading frames (ORFs) in the picA region. S1 nuclease mapping was used to identify the transcription initiation site of picA. Mutation of ORF1, but not ORF2, of the picA locus was responsible for an increased aggregation of A. tumefaciens, forming "ropes" in the presence of pea root cap cells. In addition, a potato tuber disk virulence assay indicated that a preinduced picA mutant was more virulent than was the wild-type control, a further indication that the picA locus regulates the surface properties of the bacterium in the presence of plant cells or plant cell extracts. Images PMID:1860822

  14. Assignment of the locus for Waardenburg syndrome type I to human chromosome 2q37 and possible homology to the Splotch mouse.

    PubMed Central

    Foy, C; Newton, V; Wellesley, D; Harris, R; Read, A P

    1990-01-01

    We have demonstrated close linkage between the locus for the autosomal dominant Waardenburg syndrome type I and the placental alkaline phosphatase locus on chromosome 2q37. In five families the peak lod score was 4.76 at a recombination fraction of .023. In the mouse the Splotch locus maps to near the homologous position. Splotch mice have white spotting and hearing defects, suggesting that Splotch may be the murine homologue of Waardenburg syndrome type I. PMID:2339698

  15. A Novel Quantitative Trait Locus on Mouse Chromosome 18, “era1,” Modifies the Entrainment of Circadian Rhythms

    PubMed Central

    Wisor, Jonathan P.; Striz, Martin; DeVoss, Jason; Murphy, Greer M.; Edgar, Dale M.; O'Hara, Bruce F.

    2007-01-01

    Study Objectives: The mammalian circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus conveys 24-h rhythmicity to sleep-wake cycles, locomotor activity, and other behavioral and physiological processes. The timing of rhythms relative to the light/dark (LD12:12) cycle is influenced in part by the endogenous circadian period and the time of day specific sensitivity of the clock to light. We now describe a novel circadian rhythm phenotype, and a locus influencing that phenotype, in a segregating population of mice. Methods: By crossbreeding 2 genetically distinct nocturnal strains of mice (Cast/Ei and C57BL/6J) and backcrossing the resulting progeny to Cast/Ei, we have produced a novel circadian phenotype, called early runner mice. Results: Early runner mice entrain to a light/dark cycle at an advanced phase, up to 9 hours before dark onset. This phenotype is not significantly correlated with circadian period in constant darkness and is not associated with disruption of molecular circadian rhythms in the SCN, as assessed by analysis of period gene expression. We have identified a genomic region that regulates this phenotype—a major quantitative trait locus on chromosome 18 (near D18Mit184) that we have named era1 for Early Runner Activity locus one. Phase delays caused by light exposure early in the subjective night were of smaller magnitude in backcross offspring that were homozygous Cast/Ei at D18Mit184 than in those that were heterozygous at this locus. Conclusion: Genetic variability in the circadian response to light may, in part, explain the variance in phase angle of entrainment in this segregating mouse population. Citation: Wisor JP; Striz M; DeVoss J; Murphy GM; Edgar DM; O'Hara BF. A novel quantitative trait locus on mouse chromosome 18, “era1,” modifies the entrainment of circadian rhythms. SLEEP 2007;30(10):1255-1263. PMID:17969459

  16. The RAP1GA1 locus for human Rap1-GTPase activating protein 1 maps to chromosome 1p36.1-->p35.

    PubMed

    Weiss, J; Rubinfeld, B; Polakis, P G; McCormick, F; Cavenee, W K; Arden, K C

    1994-01-01

    Using a panel of somatic cell hybrids we have mapped the locus for Rap1-GTPase activating protein 1 (RAP1GA1) to human chromosome 1. Fluorescence in situ hybridization experiments independently confirmed the chromosomal localization and refined it to 1p36.1-->p35.

  17. Identification of a genetic locus for ichthyosis vulgaris on chromosome 10q22.3-q24.2.

    PubMed

    Liu, Ping; Yang, Qingyu; Wang, Xu; Feng, Aiping; Yang, Tao; Yang, Rong; Wang, Pengyun; Yuang, Mingxiong; Liu, Mugen; Liu, Jing Yu; Wang, Qing K

    2008-06-01

    Ichthyosis vulgaris (IV) is one of the most commonly inherited disorders and has an estimated prevalence rate of 2.29% in China. To date, only one gene responsible for IV, the filaggrin gene (FLG), was identified, but genetic heterogeneity exists. In this study, two Chinese families with autosomal-dominant IV were genetically characterized. The FLG gene was first excluded as the disease-causing gene in the two families. The larger family was then characterized by genome-wide linkage analysis to identify a new genetic locus for IV. Significant linkage was identified with markers on chromosome 10q22.3-q24.2 with a maximum LOD score of 3.19. No other markers showed a LOD score of >1.5. Fine mapping defined the new genetic locus within a 20.7 cM region between markers D10S569 and D10S1709. The second family also showed positive linkage to the same 10q22.3-q24.2 region. The combined maximum LOD score in the two families was 3.95. Identification of linkage in two independent families provides strong genetic evidence that a previously unreported gene for IV is located on chromosome 10q22.3-q24.2. Future studies of the candidate genes at the 10q IV locus will identify a specific gene, which will provide insights into the pathogenesis of IV.

  18. The locus for apolipoprotein E (apoE) is close to the Lutheran (Lu) blood group locus on chromosome 19.

    PubMed

    Gedde-Dahl, T; Olaisen, B; Teisberg, P; Wilhelmy, M C; Mevåg, B; Helland, R

    1984-01-01

    Linkage has been described between the loci for apolipoprotein E (apoE) and the complement C3 (C3) on chromosome 19. C3 is known to belong to a linkage group with gene order C3-Se-Lu. The present study revealed linkage between Se and apoE with peak lod score +3.3 at recombination fraction 0.08 in males and +1.36 at 0.22 in females, and linkage between apoE and Lu with lod score +4.52 at zero recombination in sexes combined. The C3-apoE linkage gives lod score +4.00 at theta = 0.18 in males, but +0.04 at theta = 0.45 in females. Triple heterozygote families confirm that apoE is on the Se side and on the Lu side of C3. Allelic association between apoE and Lu has not been ruled out. Combining our data with published data on C3-Se and Se-Lu, this segment of chromosome 19 has an average age sex ratio of female/male recombination of 2.3.

  19. An efficient strategy for gene mapping using multipoint linkage analysis: exclusion of the multiple endocrine neoplasia 2A (MEN2A) locus from chromosome 13.

    PubMed

    Farrer, L A; Goodfellow, P J; Lamarche, C M; Franjkovic, I; Myers, S; White, B N; Holden, J J; Kidd, J R; Simpson, N E; Kidd, K K

    1987-04-01

    Members of four families in which multiple endocrine neoplasia type 2A (MEN-2A) is segregating were typed for seven DNA markers and one red cell enzyme marker on chromosome 13. Close linkage was excluded between the MEN2A locus and each marker locus tested. By means of multipoint analysis and the genetic map of chromosome 13 developed by Leppert et al., MEN2A was excluded from any position between the most proximal marker locus (D13S6) and the most distal marker locus (D13S3) and from within 12 cMorgans outside these two loci, respectively. However, the support of exclusion within an interval was diminished under the assumption of a substantially larger genetic map in females. The strategy of multipoint analysis, which excluded between 1.5 and 2.0 times more chromosome 13 than did two-point analysis, demonstrates the utility of linkage maps in mapping disease genes. PMID:2883889

  20. Haplotype analysis of DNA microsatellites tightly linked to the locus of Usher syndrome type I on chromosome 11q

    SciTech Connect

    Korostishevsky, M.; Kalinsky, H.; Seroussi, E.

    1994-09-01

    Usher syndrome type I (USHI), an autosomal recessive disorder associated with congenital sensorineural deafness and progressive visual loss, is closely linked to the D11S533 locus. The availability of 7 other polymorphic markers within few centimorgans spanning the disease locus allowed us to identify a unique and single haplotype among all carriers of USHI gene in the Samaritan kindred. Occurrence of recombination in this small chromosomal interval is rare, hindering the detection of the mitotic recombination events needed for analysis by traditional linkage methods. Attempts to order the eight loci by linkage disequilibrium models proved to be problematic. However, our haplotype analysis implied that recombinations which had arisen in past generations may be utilized in fine mapping of the USHI gene and in resolving the conflicting linkage maps previously obtained for this region. We have developed a simple algorithm for predicting the order of the microsatellites on the basis of haplotype resemblance. The following chromosomal map in which the USHI gene is closest to D11S533 (location score of 31.0 by multipoint analysis) is suggested: D11S916, GARP, D11S527, D11S533, OMP, D11S906, D11S911, D11S937. Physical mapping efforts are currently directed to verify and to detail the map of this chromosomal region.

  1. Potential linkage disequilibrium between schizophrenia and locus D22S278 on the long arm of chromosome 22

    SciTech Connect

    Moises, H.W.; Yang, L.; Havsteen, B.

    1995-10-09

    Locus D22S278 at 22q12 has been implicated in schizophrenia by sib-pair analysis. In order to replicate these results, we performed the transmission test for linkage disequilibrium (TDT) in 113 unrelated schizophrenic patients and their 226 parents. Evidence for potential linkage disequilibrium was obtained between schizophrenia and allele 243 of the marker AFM 182xd12 at the locus D22S278 (P = 0.02). The results of our study suggest a detectable oligogenic gene in a multigene system for schizophrenia closely linked to D22S278 on the long arm of chromosome 22. If confirmed by others, this finding could lead to the identification of a schizophrenia susceptibility gene. 12 refs., 1 tab.

  2. Association Between Genetic Variants on Chromosome 15q25 Locus and Objective Measures of Tobacco Exposure

    PubMed Central

    Timofeeva, Maria N.; Morris, Richard W.; Prieto-Merino, David; Sattar, Naveed; Brennan, Paul; Johnstone, Elaine C.; Relton, Caroline; Johnson, Paul C. D.; Walther, Donna; Whincup, Peter H.; Casas, Juan P.; Uhl, George R.; Vineis, Paolo; Padmanabhan, Sandosh; Jefferis, Barbara J.; Amuzu, Antoinette; Riboli, Elio; Upton, Mark N.; Aveyard, Paul; Ebrahim, Shah; Hingorani, Aroon D.; Watt, Graham; Palmer, Tom M.; Timpson, Nicholas J.; Davey Smith, George

    2012-01-01

    Background Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure. Methods We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730–rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730–rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided. Results Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730–rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10−6) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10−11). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs

  3. Cia27 is a novel non-MHC arthritis severity locus on rat chromosome 10 syntenic to the rheumatoid arthritis 17q22-q25 locus.

    PubMed

    Brenner, M; Laragione, T; Yarlett, N C; Li, W; Mello, A; Gulko, P S

    2006-07-01

    Cia27 on rat chromosome 10 is a collagen-induced arthritis (CIA) severity quantitative trait locus originally identified in a study of (DA x ACI) F2. As an initial step towards the positional cloning of the Cia27 gene, a 17 cM (21 Mb) interval from the DA strain (arthritis-susceptible) containing the two-logarithm of odds support interval comprising Cia27 was introgressed into the ACI (arthritis-resistant) background through genotype-guided congenic breeding. ACI.DA(Cia27) congenics developed a significantly more severe form of arthritis (CIA), with a 5.9-fold increase in median arthritis severity index, a parameter known to correlate with synovial inflammation, and cartilage and bone erosions, compared with ACI (P< or =0.001). The arthritis severity enhancing effect could be detected from day 21 onwards. Rats heterozygous at the congenic interval developed a disease similar to ACI rats, suggesting that DA alleles operate in a recessive manner. Levels of autoantibodies anti-rat type II collagen did not correlate with arthritis severity. Synovial tissue mRNA levels of interleukin-1beta (IL-1beta) were significantly increased in ACI.DA(Cia27) congenics compared with ACI. These results demonstrate that Cia27 harbors a novel arthritis severity regulatory gene. The identification of this gene should facilitate the identification of the rheumatoid arthritis gene mapped to the human syntenic region on chromosome 17q22-q25. PMID:16691185

  4. A Locus for Hereditary Sensory Neuropathy with Cough and Gastroesophageal Reflux on Chromosome 3p22-p24

    PubMed Central

    Kok, C.; Kennerson, M. L.; Spring, P. J.; Ing, A. J.; Pollard, J. D.; Nicholson, G. A.

    2003-01-01

    Hereditary sensory neuropathy type I (HSN I) is a group of dominantly inherited degenerative disorders of peripheral nerve in which sensory features are more prominent than motor involvement. We have described a new form of HSN I that is associated with cough and gastroesophageal reflux. To map the chromosomal location of the gene causing the disorder, a 10-cM genome screen was undertaken in a large Australian family. Two-point analysis showed linkage to chromosome 3p22-p24 (Zmax=3.51 at recombination fraction (θ) 0.0 for marker D3S2338). A second family with a similar phenotype shares a different disease haplotype but segregates at the same locus. Extended haplotype analysis has refined the region to a 3.42-cM interval, flanked by markers D3S2336 and D3S1266. PMID:12870133

  5. 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.

  6. Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding the Cu/Zn superoxide dismutase.

    PubMed Central

    Levanon, D; Lieman-Hurwitz, J; Dafni, N; Wigderson, M; Sherman, L; Bernstein, Y; Laver-Rudich, Z; Danciger, E; Stein, O; Groner, Y

    1985-01-01

    The SOD-1 gene on chromosome 21 and approximately 100 kb of chromosomal DNA from the 21q22 region have been isolated and characterized. The gene which is present as a single copy per haploid genome spans 11 kb of chromosomal DNA. Heteroduplex analysis and DNA sequencing reveals five rather small exons and four introns that interrupt the coding region. The donor sequence at the first intron contains an unusual variant dinucleotide 5'-G-C, rather than the highly conserved 5'-GT. The unusual splice junction is functional in vivo since it was detected in both alleles of the SOD-1 gene, which were defined by differences in the length of restriction endonuclease fragments (RFLPs) that hybridize to the cDNA probe. Genomic blots of human DNA isolated from cells trisomic for chromosome 21 (Down's syndrome patients) show the normal pattern of bands. At the 5' end of gene there are the 'TATA' and 'CAT' promoter sequences as well as four copies of the -GGCGGG- hexanucleotide. Two of these -GC- elements are contained within a 13 nucleotide inverted repeat that could form a stem-loop structure with stability of -33 kcal. The 3'-non coding region of the gene contains five short open reading-frames starting with ATG and terminating with stop codons. Images Fig. 1. Fig. 3. Fig. 7. PMID:3160582

  7. The LOSS OF APOMEIOSIS (LOA) locus in Hieracium praealtum can function independently of the associated large-scale repetitive chromosomal structure.

    PubMed

    Kotani, Yoshiko; Henderson, Steven T; Suzuki, Go; Johnson, Susan D; Okada, Takashi; Siddons, Hayley; Mukai, Yasuhiko; Koltunow, Anna M G

    2014-02-01

    Apomixis or asexual seed formation in Hieracium praealtum (Asteraceae) is controlled by two independent dominant loci. One of these, the LOSS OF APOMEIOSIS (LOA) locus, controls apomixis initiation, mitotic embryo sac formation (apospory) and suppression of the sexual pathway. The LOA locus is found near the end of a hemizygous chromosome surrounded by extensive repeats extending along the chromosome arm. Similar apomixis-carrying chromosome structures have been found in some apomictic grasses, suggesting that the extensive repetitive sequences may be functionally relevant to apomixis. Fluorescence in situ hybridization (FISH) was used to examine chromosomes of apomeiosis deletion mutants and rare recombinants in the critical LOA region arising from a cross between sexual Hieracium pilosella and apomictic H. praealtum. The combined analyses of aposporous and nonaposporous recombinant progeny and chromosomal karyotypes were used to determine that the functional LOA locus can be genetically separated from the very extensive repeat regions found on the LOA-carrying chromosome. The large-scale repetitive sequences associated with the LOA locus in H. praealtum are not essential for apospory or suppression of sexual megasporogenesis (female meiosis). PMID:24400904

  8. Identification of a locus for type I punctate palmoplantar keratoderma on chromosome 15q22–q24

    PubMed Central

    Martinez-Mir, A; Zlotogorski, A; Londono, D; Gordon, D; Grunn, A; Uribe, E; Horev, L; Ruiz, I; Davalos, N; Alayan, O; Liu, J; Gilliam, T; Salas-Alanis, J; Christiano, A

    2003-01-01

    Background: The identification of the molecular basis of disorders of keratinisation has significantly advanced our understanding of skin biology, revealing new information on key structures in the skin, such as the intermediate filaments, desmosomes, and gap junctions. Among these disorders, there is an extraordinarily heterogeneous group known as palmoplantar keratodermas (PPK), for which only a few molecular defects have been described. A particular form of PPK, known as punctate PPK, has been described in a few large autosomal dominant pedigrees, but its genetic basis has yet to be identified. Aim: Identification of the gene for punctate PPK. Methods: Clinical examination and linkage analysis in three families with punctate PPK. Results: A genomewide scan was performed on an extended autosomal dominant pedigree, and linkage to chromosome 15q22–q24 was identified. With the addition of two new families with the same phenotype, we confirmed the mapping of the locus for punctate PPK to a 9.98 cM interval, flanked by markers D15S534 and D15S818 (maximum two point lod score of 4.93 at θ = 0 for marker D15S988). Conclusions: We report the clinical and genetic findings in three pedigrees with the punctate form of PPK. We have mapped a genetic locus for this phenotype to chromosome 15q22–q24, which indicates the identification of a new gene involved in skin integrity. PMID:14684683

  9. 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.

  10. Loss of heterozygosity occurs at the D11S29 locus on chromosome 11q23 in invasive cervical carcinoma.

    PubMed Central

    Bethwaite, P. B.; Koreth, J.; Herrington, C. S.; McGee, J. O.

    1995-01-01

    Allelotypic detection of loss of heterozygosity (LOH) has been used to identify putative tumour-suppressor genes. Loci on human chromosome 11q23 are frequently altered in malignant disease, and LOH has been reported at an anonymous D11S29 locus at 11q23 in a proportion of breast and ovarian cancers and malignant melanomas. Previous studies have reported a high frequency of LOH in cervical carcinoma mapping to 11q23. Using polymerase chain reaction techniques employing probes for a recently described polymorphic dinucleotide microsatellite within this locus, we have searched for LOH in 69 cases of invasive cervical carcinoma. Genomic material was microdissected from sections cut from archival paraffin-embedded material, using the patients' constitutional genotype as a control Sixty-two (90%) of the cases were informative, and LOH occurred in 25/62 (40%) of tumours. Loss of an arm or single chromosome 11 is a well-recognised event in cervical carcinoma, and by employing other microsatellite polymorphisms mapping to 11q13 and 11p11-p12 we excluded those cases with widespread allelic loss. By doing so, LOH at D11S29 was found in 16/53 (30%) of tumours. The findings suggest a putative tumour-suppressor gene on 11q involved in cervical carcinogenesis. Images Figure 1 Figure 2 PMID:7710949

  11. 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).

  12. High-resolution genetic mapping of the sucrose octaacetate taste aversion (Soa) locus on mouse Chromosome 6

    PubMed Central

    Bachmanov, Alexander A.; Li, Xia; Li, Shanru; Neira, Mauricio; Beauchamp, Gary K.; Azen, Edwin A.

    2013-01-01

    An acetylated sugar, sucrose octaacetate (SOA), tastes bitter to humans and has an aversive taste to at least some mice and other animals. In mice, taste aversion to SOA depends on allelic variation of a single locus, Soa. Three Soa alleles determine ‘taster’ (Soaa), ‘nontaster’ (Soab), and ‘demitaster’ (Soac) phenotypes of taste sensitivity to SOA. Although Soa has been mapped to distal Chromosome (Chr) 6, the limits of the Soa region have not been defined. In this study, mice from congenic strains SW.B6-Soab, B6.SW-Soaa, and C3.SW-Soaa/c and from an outbred CFW strain were genotyped with polymorphic markers on Chr 6. In the congenic strains, the limits of introgressed donor fragments were determined. In the outbred mice, linkage disequilibrium and haplotype analyses were conducted. Positions of the markers were further resolved by using radiation hybrid mapping. The results show that the Soa locus is contained in a ~1-cM (3.3–4.9 Mb) region including the Prp locus. PMID:11641717

  13. The existence of Usher syndrome type III proven by assignment of its locus to chromosome 3q by linkage

    SciTech Connect

    Sankila, E.M.; Aittomaeki, K.; Kaeaeriaeinen, H.

    1994-09-01

    Usher syndromes (USH) are genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Usher syndrome type III (USH3) is characterized by progressive bilateral sensorineural deafness and progressive pigmentary retinopathy leading to blindness. USH3 has been conservatively estimated to comprise 2% of the three clinical USH types, and its existence has even been questioned. However, based on clinical criteria, in Finland 42% of USH patients have USH3 suggesting gene enrichment by a founder effect. Genes whose defects cause USH have so far been mapped to four different locations in three chromosomes. We have excluded the previously mapped USH regions as the site of USH3 disease locus. Systematic search for USH3 by genetic linkage analyses of 11 multiple affected families using highly polymorphic microsatellite markers revealed significant linkage with five markers mapping to chromosome 3q. Two-point lod scores at zero recombination distance were 5.24 for D3S1308, and 7.71 for D3S1299, respectively. Multipoint linkage analysis gave a maximum lod score of 8.68 at D3S1299 assigning USH3 to the 4 cM interval between markers D3S1555 and D3S1279 in 3q21-25. Of 20 parental disease chromosomes, 15 had identical alleles at three marker loci covering 3 cM genetic distance and the putative USH3 mutation. These findings prove the existence of USH3 as a distinct entity, pinpoint a fifth USH locus, and suggest enrichment of a major mutation in the isolated Finnish population.

  14. Autosomal dominant aniridia: probable linkage to acid phosphatase-1 locus on chromosome 2.

    PubMed Central

    Ferrell, R E; Chakravarti, A; Hittner, H M; Riccardi, V M

    1980-01-01

    Maximum likelihood analysis for linkage between autosomal dominant aniridia and 12 biochemical and serological markers in a single large family showed a probable linkage between autosomal dominant aniridia and the enzyme acid phosphatase-1. The presence of an autosomal dominant aniridia gene linked to acid phosphatase-1 on chromosome arm 2p and the existence of an aniridia syndrome resulting from deletion of band 13 of the short arm of chromosome 11 establishes a chromosome basis for genetic heterogeneity of aniridia phenotypes. PMID:6929510

  15. 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

  16. Identification of TERRA locus unveils a telomere protection role through association to nearly all chromosomes.

    PubMed

    López de Silanes, Isabel; Graña, Osvaldo; De Bonis, Maria Luigia; Dominguez, Orlando; Pisano, David G; Blasco, Maria A

    2014-09-03

    Telomeric RNAs (TERRAs) are UUAGGG repeat-containing RNAs that are transcribed from the subtelomere towards the telomere. The precise genomic origin of TERRA has remained elusive. Using a whole-genome RNA-sequencing approach, we identify novel mouse transcripts arising mainly from the subtelomere of chromosome 18, and to a lesser extend chromosome 9, that resemble TERRA in several key aspects. Those transcripts contain UUAGGG-repeats and are heterogeneous in size, fluctuate in abundance in a TERRA-like manner during the cell cycle, are bound by TERRA RNA-binding proteins and are regulated in a manner similar to TERRA in response to stress and the induction of pluripotency. These transcripts are also found to associate with nearly all chromosome ends and downregulation of the transcripts that originate from chromosome 18 causes a reduction in TERRA abundance. Interestingly, downregulation of either chromosome 18 transcripts or TERRA results in increased number of telomere dysfunction-induced foci, suggesting a protective role at telomeres.

  17. Refinement of the cone-rod retinal dystrophy locus on chromosome 19q

    SciTech Connect

    Gregory, C.Y.; Evans, K.; Bhattacharya, S.S.; Whittaker, J.L.; Fryer, A.; Weissenbach, J.

    1994-11-01

    Cone-rod dystrophy (CRD) is a severe example of an inherited retinal dystrophy: ophthalmic diseases that as a group constitute the commonest causes of blindness in children in the developed world and account for a significant proportion of visual handicap in adults. Two case reports suggested loci for CRD-causing genes on chromosomes 18q and chromosome 17q. Recently, we reported the results of a total genome search that localized an autosomal dominant form of CRD to chromosome 19q in the region 19q13.1-q13.2. Since then, using data from a short tandem repeat-polymorphism linkage map of chromosome 19 and recently developed microsatellite markers in this region, we have been able to further refine the localization of the chromosome 19q CRD-causing gene. Seven new microsatellite markers were used to genotype 34 affected subjects, 22 unaffected subjects, and 15 spouses. Two-point, multipoint, and FASTMAP analyses were performed. 11 refs., 1 tab.

  18. Genetic and physical mapping at the limb-girdle muscular dystrophy locus (LGMD2B) on chromosome 2p

    SciTech Connect

    Bashir, R.; Keers, S.; Strachan, T.

    1996-04-01

    The limb-girdle muscular dystrophies (LGMD) are a genetically heterogeneous group of disorders, different forms of which have been mapped to at least six distinct genetic loci. We have mapped to at least six distinct genetic loci. We have mapped an autosomal recessive form of LGMD (LGMD2B) to chromosome 2p13. Two other conditions have been shown to map to this region or to the homologous region in mouse: a gene for a form of autosomal recessive distal muscular dystrophy, Miyoshi myopathy, shows linkage to the same markers on chromosome 2p as LGMD2B, and an autosomal recessive mouse mutation mnd2, in which there is rapidly progressive paralysis and muscle atrophy, has been mapped to mouse chromosome 6 to a region showing conserved synteny with human chromosome 2p12-p13. We have assembled a 6-cM YAC contig spanning the LGMD2B locus and have mapped seven genes and 13 anonymous polymorphic microsatellites to it. Using haplotype analysis in the linked families, we have narrowed our region of interest to a 0-cM interval between D2S2113 and D2S145, which does not overlap with the critical region for mnd2 in mouse. Use of these most closely linked markers will help to determine the relationship between LGMD2B and Miyoshi myopathy. YACs selected from our contig will be the starting point for the cloning of the LGMD2B gene and thereby establish the biological basis for this form of muscular dystrophy and its relationship with the other limb-girdle muscular dystrophies. 26 refs., 6 figs.

  19. New polymorphic markers in the vicinity of the pearl locus on mouse chromosome 13.

    PubMed

    Xu, H P; Yanak, B L; Wigler, M H; Gorin, M B

    1996-01-01

    We have used a Mus domesticus/-Mus spretus congenic animal that was selected for retention of Mus spretus DNA around the pearl locus to create a highly polymorphic region suitable for screening new markers. Representation difference analysis (RDA) was performed with either DNA from the congenic animal or C57BL/6J as the driver for subtraction. Four clones were identified, characterized, and converted to PCR-based polymorphic markers. Three of the four markers equally subdivide a 10-cM interval containing the pearl locus, with the fourth located centromeric to it. These markers have been placed on the mouse genetic map by use of an interspecific backcross panel between Mus domesticus (C57BL/6J) and Mus spretus generated by The Jackson Laboratory.

  20. Reflections on the evidence for a vulnerability locus for Schizophrenia on chromosome 6p24-22

    SciTech Connect

    Kendler, K.S.; Straub, R.E.; MacLean, C.J.

    1996-04-09

    A recent series of studies have attempted to replicate evidence for a vulnerability locus for schizophrenia on chromosome 6p initially detected in the Irish Study of High-Density Schizophrenia Families (ISHDSF). Here, we want to comment briefly on these findings and respond to some of the issues raised in the preceding article by Baron. We disclaim, however, any pretensions to a definitive interpretation of the available evidence. Our level of ignorance in the interpretation of linkage evidence for complex psychiatric syndromes is too profound. Rather, we seek to make educated guesses on the basis of our understanding of the principles of linkage analysis, on our knowledge of the problems of statistical inference and on our intuition of how genes might influence vulnerability to complex human behavioral traits. 27 refs.

  1. The spinocerebellar ataxia 2 locus is located within a 3-cm interval on chromosome 12q23-24.1

    SciTech Connect

    Allotey, R.; Twells, R.; Cemal, C.

    1995-07-01

    The autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of neurodegenerative disorders characterized by a predominantly cerebellar syndrome of onset with gait ataxia, dysarthria, dysmetria, and dysdiadochokinesia. Pathologically, the disorders are characterized by premature neuronal loss in the cerebellar cortex and the inferior olivary and pontine nuclei, with degeneration of the spinal cord. We have previously assigned the spinocerebellar ataxia 2 locus to chromosome 12q23-24.1, within a 31-cM interval flanked by the loci D12S58 and PLA2. Linkage to SCA2 has been demonstrated in pedigrees from Europe, Japan, and North America, the latter serving to refine the candidate region to a 16-cM interval. We report here genetic analysis undertaken between SCA2 and nine microsatellite loci known to span 8 cM within this interval. 12 refs., 2 figs., 1 tab.

  2. High-resolution linkage map of mouse chromosome 13 in the vicinity of the host resistance locus Lgn1

    SciTech Connect

    Beckers, M.C.; Ernst, E.; Diez, E.

    1997-02-01

    Natural resistance of inbred mouse strains to infection with Legionella pneumophila is controlled by the expression of a single dominant gene on chromosome 13, designated Lgn1. The genetic difference at Lgn1 is phenotypically expressed as the presence or absence of intracellular replication of L. pneumophila in host macrophages. In our effort to identify the Lgn1 gene by positional cloning, we have generated a high-resolution linkage map of the Lgn1 chromosomal region. For this, we have carried out extensive segregation analysis in a total of 1270 (A/J x C57BL/6J) X A/J informative backcross mice segregating the resistance allele of C57BL/6J and the susceptibility allele of A/J. Additional segregation analyses were carried out in three preexisting panels of C57BL/6J X Mus spretus interspecific backcross mice. A total of 39 DNA markers were mapped within an interval of approximately 30 cM overlapping the Lgn1 region. Combined pedigree analyses for the 5.4-cM segment overlapping Lgn1 indicated the locus order and the interlocus distances (in cM): D13Mit128-(1.4)-D13Mit194-(0.1)-D13Mit147-(0.9)-Dl3Mit36-(0.9)-D13Mit146-(0.2)-Lgn1/D 13Mit37-(1.0)-D13Mit70. Additional genetic linkage studies of markers not informative in the A/J X C57BL/6J cross positioned D13Mit30, -72, -195, and -203, D13Gor4, D13Hun35, and Mtap5 in the immediate vicinity of the Lgn1 locus. The marker density and resolution of this genetic linkage map should allow the construction of a physical map of the region and the isolation of YAC clones overlapping the gene. 60 refs., 2 figs., 2 tabs.

  3. 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.

  4. A novel locus on canine chromosome 13 is associated with cataract in the Australian Shepherd breed of domestic dog.

    PubMed

    Ricketts, Sally L; Pettitt, Louise; McLaughlin, Bryan; Jenkins, Christopher A; Mellersh, Cathryn S

    2015-06-01

    Hereditary cataract is a common ocular disorder in the purebred dog population and is a leading cause of visual impairment and blindness in dogs. Despite this, little is known to date about the genetics underlying this condition. We have used a genome-wide association study and targeted resequencing approach to identify a novel locus for cataracts in the Australian Shepherd breed of dog, using dogs that are clear of an HSF4 mutation, previously identified as the major susceptibility locus in this breed. Cataract cases were defined as dogs with bilateral posterior cataracts, or bilateral nuclear cataracts. Controls were at least 8 years of age with no evidence of cataracts or other ocular abnormality. Using 15 bilateral posterior polar cataract cases and 68 controls, we identified a genome-wide statistical association for cataracts in the Australian Shepherd on canine chromosome 13 at 46.4 Mb (P value: 1.5 × 10(-7)). We sequenced the 14.16 Mb associated region in ten Australian Shepherds to search for possible causal variants underlying the association signal and conducted additional fine-mapping of the region by genotyping 28 intronic variants that segregated correctly in our ten sequenced dogs. From this analysis, the strongest associated variants were located in intron 5 of the SCFD2 gene. Further study will require analysis of additional cases and controls and ocular tissue from dogs affected with bilateral cataracts that are free of the HSF4 mutation.

  5. A physical map across chromosome 11q22-q23 containing the major locus for ataxia telangiectasia

    SciTech Connect

    Ambrose, H.J.; Byrd, P.J.; McConville, C.M.

    1994-06-01

    The authors have constructed a long-range physical map for 12 markers, including genes for GRIA3, IL1BC, and ACAT, across 9 MB of chromosome 11q22-q23 in the region of the major locus for ataxia-telangiectasia (A-T). The markers fall into the proximal and distal groups with respect to the centromere. They have linked the proximal and distal groups by hybridization to a 2.7-Mb NotI fragment and and 4.6-Mb MluI fragment. The following locus order was obtained: centromere-CJ52.75-J12.1C2-Y11B11R-IL1BC-hbcDNA-GRIA4-CJ52.3-Y11B29L-ACAT-CJ52.193-J12.8-Y11B06R-telomere. They show that hbcDNA/GRIA4 and CJ52.3 are very closely linked to each end, respectively, of the 2.7-Mb NotI fragment, thereby fixing the position of the complete contig. The results indicate that the gene for A-T is flanked by the markers GRIA4 and J12.8, which are no more than 3 Mb apart, on a 4.6-Mb MluI fragment. The physical map allows rapid positioning of markers, and this will facilitate the construction of a YAC contig across the region. 25 refs., 4 figs., 4 tabs.

  6. Selective intestinal malabsorption of vitamin B12 displays recessive Mendelian inheritance: Assignment of a locus to chromosome 10 by linkage

    SciTech Connect

    Aminoff, M.; Tahvanainen, E.; Chapelle, A. de la

    1995-10-01

    Juvenile megaloblastic anemia caused by selective intestinal malabsorption of vitamin B12 has been considered a distinct condition displaying autosomal recessive inheritance. It appears to have a worldwide distribution, and comparatively high incidences were reported 30 years ago in Finland and Norway. More recently, the Mendelian inheritance of the condition has been questioned because almost no new cases have occurred in these populations. Here we report linkage studies assigning a recessive-gene locus for the disease to chromosome 10 in previously diagnosed multiplex families from Finland and Norway, proving the Mendelian mode of inheritance. The locus is tentatively assigned to the 6-cM interval between markers D10S548 and D10S466, with a multipoint maximum lod score (Z{sub max}) of 5.36 near marker D10S1477. By haplotype analysis, the healthy sibs in these families did not appear to constitute any examples of nonpenetrance. We hypothesize that the paucity of new cases in these populations is due either to a dietary effect on the gene penetrance that has changed with time, or to a drop in the birth rate in subpopulations showing enrichment of the mutation, or to both of these causes. 38 refs., 4 figs., 2 tabs.

  7. Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice

    PubMed Central

    Nelson, Theodore M; Munger, Steven D; Boughter, John D

    2005-01-01

    Background The detection of bitter-tasting compounds by the gustatory system is thought to alert animals to the presence of potentially toxic food. Some, if not all, bitter stimuli activate specific taste receptors, the T2Rs, which are expressed in subsets of taste receptor cells on the tongue and palate. However, there is evidence for both receptor-dependent and -independent transduction mechanisms for a number of bitter stimuli, including quinine hydrochloride (QHCl) and denatonium benzoate (DB). Results We used brief-access behavioral taste testing of BXD/Ty recombinant inbred (RI) mouse strains to map the major quantitative trait locus (QTL) for taste sensitivity to QHCl. This QTL is restricted to a ~5 Mb interval on chromosome 6 that includes 24 genes encoding T2Rs (Tas2rs). Tas2rs at this locus display in total 307 coding region single nucleotide polymorphisms (SNPs) between the two BXD/Ty RI parental strains, C57BL/6J (quinine-sensitive) and DBA/2J (quinine insensitive); approximately 50% of these mutations are silent. Individual RI lines contain exclusively either C57BL/6J or DBA/2J Tas2r alleles at this locus, and RI lines containing C57BL/6J Tas2r alleles are more sensitive to QHCl than are lines containing DBA/2J alleles. Thus, the entire Tas2r cluster comprises a large haplotype that correlates with quinine taster status. Conclusion These studies, the first using a taste-salient assay to map the major QTL for quinine taste, indicate that a T2R-dependent transduction cascade is responsible for the majority of strain variance in quinine taste sensitivity. Furthermore, the large number of polymorphisms within coding exons of the Tas2r cluster, coupled with evidence that inbred strains exhibit largely similar bitter taste phenotypes, suggest that T2R receptors are quite tolerant to variation. PMID:15938754

  8. Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree

    SciTech Connect

    Silverman, J.M.; Altstiel, L.D.; Siever, L.J.

    1996-04-09

    We attempted to identify a locus for schizophrenia and related disorders in 24 nuclear families of schizophrenic probands using a predefined classification system for affected cases that included those disorders most clearly identified as sharing a genetic relationship with schizophrenia-schizoaffective disorder and schizotypal personality disorder. Initially, we evaluated 8 markers on chromosome 5 on the first 12 families with available genotyping and diagnostic assessments and, assuming autosomal dominant transmission, found a lod score of 2.67 for the D5S111 locus (5p14.1-13.1) in one large nuclear family (no. 17; sibship: n = 12; schizophrenia: n = 3; schizotypal personality disorder: n = 2); the other 11 families were much smaller, less complete, and provided little additional information. Other branches of no. 17 were then assessed and the 2-point lod score for family 17 rose to 3.72; using multipoint analysis the lod score in 17 was 4.37. When only schizophrenia was used to define affectedness, the positive evidence for linkage to D5S111 was greatly reduced. Sensitivity analysis indicated that the lod score is heavily dependent upon the predefined diagnostic criteria. Our studies of other families of schizophrenic probands eventually totalled 23, but linkage to D5S111 in these yielded a -2.41 lod score. The results provide evidence for genetic linkage of the D5S111 locus to schizophrenia and related disorders in one family. It may be of interest that over several generations, almost all the ancestors of family 17 could be traced back to a small, relatively isolated, hill region of Puerto Rico. 74 refs., 2 figs., 2 tabs.

  9. A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3.

    PubMed Central

    De Michele, G; De Fusco, M; Cavalcanti, F; Filla, A; Marconi, R; Volpe, G; Monticelli, A; Ballabio, A; Casari, G; Cocozza, S

    1998-01-01

    Hereditary spastic paraplegia is a genetically and phenotypically heterogeneous disorder. Both pure and complicated forms have been described, with autosomal dominant, autosomal recessive, and X-linked inheritance. Various loci (SPG1-SPG6) associated with this disorder have been mapped. Here, we report linkage analysis of a large consanguineous family affected with autosomal recessive spastic paraplegia with age at onset of 25-42 years. Linkage analysis of this family excluded all previously described spastic paraplegia loci. A genomewide linkage analysis showed evidence of linkage to chromosome 16q24.3, with markers D16S413 (maximum LOD score 3.37 at recombination fraction [theta] of .00) and D16S303 (maximum LOD score 3.74 at straight theta=.00). Multipoint analysis localized the disease gene in the most telomeric region, with a LOD score of 4.2. These data indicate the presence of a new locus linked to pure recessive spastic paraplegia, on chromosome 16q24.3, within a candidate region of 6 cM. PMID:9634528

  10. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.

    PubMed

    Su, Zhan; Gay, Laura J; Strange, Amy; Palles, Claire; Band, Gavin; Whiteman, David C; Lescai, Francesco; Langford, Cordelia; Nanji, Manoj; Edkins, Sarah; van der Winkel, Anouk; Levine, David; Sasieni, Peter; Bellenguez, Céline; Howarth, Kimberley; Freeman, Colin; Trudgill, Nigel; Tucker, Art T; Pirinen, Matti; Peppelenbosch, Maikel P; van der Laan, Luc J W; Kuipers, Ernst J; Drenth, Joost P H; Peters, Wilbert H; Reynolds, John V; Kelleher, Dermot P; McManus, Ross; Grabsch, Heike; Prenen, Hans; Bisschops, Raf; Krishnadath, Kausila; Siersema, Peter D; van Baal, Jantine W P M; Middleton, Mark; Petty, Russell; Gillies, Richard; Burch, Nicola; Bhandari, Pradeep; Paterson, Stuart; Edwards, Cathryn; Penman, Ian; Vaidya, Kishor; Ang, Yeng; Murray, Iain; Patel, Praful; Ye, Weimin; Mullins, Paul; Wu, Anna H; Bird, Nigel C; Dallal, Helen; Shaheen, Nicholas J; Murray, Liam J; Koss, Konrad; Bernstein, Leslie; Romero, Yvonne; Hardie, Laura J; Zhang, Rui; Winter, Helen; Corley, Douglas A; Panter, Simon; Risch, Harvey A; Reid, Brian J; Sargeant, Ian; Gammon, Marilie D; Smart, Howard; Dhar, Anjan; McMurtry, Hugh; Ali, Haythem; Liu, Geoffrey; Casson, Alan G; Chow, Wong-Ho; Rutter, Matt; Tawil, Ashref; Morris, Danielle; Nwokolo, Chuka; Isaacs, Peter; Rodgers, Colin; Ragunath, Krish; MacDonald, Chris; Haigh, Chris; Monk, David; Davies, Gareth; Wajed, Saj; Johnston, David; Gibbons, Michael; Cullen, Sue; Church, Nicholas; Langley, Ruth; Griffin, Michael; Alderson, Derek; Deloukas, Panos; Hunt, Sarah E; Gray, Emma; Dronov, Serge; Potter, Simon C; Tashakkori-Ghanbaria, Avazeh; Anderson, Mark; Brooks, Claire; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden; Duncanson, Audrey; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin N A; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas; Trynka, Gosia; Wijmenga, Cisca; Cazier, Jean-Baptiste; Atherfold, Paul; Nicholson, Anna M; Gellatly, Nichola L; Glancy, Deborah; Cooper, Sheldon C; Cunningham, David; Lind, Tore; Hapeshi, Julie; Ferry, David; Rathbone, Barrie; Brown, Julia; Love, Sharon; Attwood, Stephen; MacGregor, Stuart; Watson, Peter; Sanders, Scott; Ek, Weronica; Harrison, Rebecca F; Moayyedi, Paul; de Caestecker, John; Barr, Hugh; Stupka, Elia; Vaughan, Thomas L; Peltonen, Leena; Spencer, Chris C A; Tomlinson, Ian; Donnelly, Peter; Jankowski, Janusz A Z

    2012-10-01

    Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

  11. A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22)

    PubMed Central

    Lafferty, A.; Torpy, D.; Stowasser, M.; Taymans, S.; Lin, J. P.; Huggard, P.; Gordon, R.; Stratakis, C.

    2000-01-01

    Familial hyperaldosteronism type II (FH-II) is caused by adrenocortical hyperplasia or aldosteronoma or both and is frequently transmitted in an autosomal dominant fashion. Unlike FH type I (FH-I), which results from fusion of the CYP11B1 and CYP11B2 genes, hyperaldosteronism in FH-II is not glucocorticoid remediable. A large family with FH-II was used for a genome wide search and its members were evaluated by measuring the aldosterone:renin ratio. In those with an increased ratio, FH-II was confirmed by fludrocortisone suppression testing. After excluding most of the genome, genetic linkage was identified with a maximum two point lod score of 3.26 at θ=0, between FH-II in this family and the polymorphic markers D7S511, D7S517, and GATA24F03 on chromosome 7, a region that corresponds to cytogenetic band 7p22. This is the first identified locus for FH-II; its molecular elucidation may provide further insight into the aetiology of primary aldosteronism.


Keywords: chromosome 7; aldosterone; familial hyperaldosteronism type II; hypertension PMID:11073536

  12. A radiation hybrid map of human chromosome 11q22-q23 containing the ataxia-telangiectasia disease locus

    SciTech Connect

    Richard, C.W. III; Cox, D.R.; Kapp, L.; Murnane, J. ); Cornelis, F.; Julier, C.; Lathrop, M.; James, M.R. )

    1993-07-01

    The authors describe a high-resolution radiation hybrid map of human chromosome 11q22-q23 containing the ataxia-telangiectasia (AT) disease gene loci. The order and intermarker distances of 32 chromosome 11q22-q23 markers were determined by a multipoint maximum likelihood method analysis of the cosegregation of markers in 100 radiation hybrids. The radiation hybrid map of polymorphic loci was consistent with genetic linkage maps of common markers. Several genes, including [alpha]B-crystallin, adrenal ferrodoxin, CBL2, collagenase, dopamine receptor type 2, neural cell adhesion molecule, progesterone receptor, and stromelysins 1 and 2, were placed in relation to previously ordered, genetically mapped polymorphic loci. Five new markers ([alpha]B-crystallin, adrenal ferrodoxin, CJ52.114, CJ52.3, and D11S535) were ordered within the current published flanking markers for the AT group A and group C disease loci. A candidate AT group D gene (ATDC) identified by Kapp et al. was mapped telomeric to THY1, outside the flanking markers identified by multipoint linkage analysis for the major AT locus. 29 refs., 1 fig., 2 tabs.

  13. Tandem amplification of a chromosomal segment harboring 5-enolpyruvylshikimate-3-phosphate synthase locus confers glyphosate resistance in Kochia scoparia.

    PubMed

    Jugulam, Mithila; Niehues, Kindsey; Godar, Amar S; Koo, Dal-Hoe; Danilova, Tatiana; Friebe, Bernd; Sehgal, Sunish; Varanasi, Vijay K; Wiersma, Andrew; Westra, Philip; Stahlman, Phillip W; Gill, Bikram S

    2014-11-01

    Recent rapid evolution and spread of resistance to the most extensively used herbicide, glyphosate, is a major threat to global crop production. Genetic mechanisms by which weeds evolve resistance to herbicides largely determine the level of resistance and the rate of evolution of resistance. In a previous study, we determined that glyphosate resistance in Kochia scoparia is due to the amplification of the 5-Enolpyruvylshikimate-3-Phosphate Synthase (EPSPS) gene, the enzyme target of glyphosate. Here, we investigated the genomic organization of the amplified EPSPS copies using fluorescence in situ hybridization (FISH) and extended DNA fiber (Fiber FISH) on K. scoparia chromosomes. In both glyphosate-resistant K. scoparia populations tested (GR1 and GR2), FISH results displayed a single and prominent hybridization site of the EPSPS gene localized on the distal end of one pair of homologous metaphase chromosomes compared with a faint hybridization site in glyphosate-susceptible samples (GS1 and GS2). Fiber FISH displayed 10 copies of the EPSPS gene (approximately 5 kb) arranged in tandem configuration approximately 40 to 70 kb apart, with one copy in an inverted orientation in GR2. In agreement with FISH results, segregation of EPSPS copies followed single-locus inheritance in GR1 population. This is the first report of tandem target gene amplification conferring field-evolved herbicide resistance in weed populations.

  14. Tandem amplification of a chromosomal segment harboring 5-enolpyruvylshikimate-3-phosphate synthase locus confers glyphosate resistance in Kochia scoparia.

    PubMed

    Jugulam, Mithila; Niehues, Kindsey; Godar, Amar S; Koo, Dal-Hoe; Danilova, Tatiana; Friebe, Bernd; Sehgal, Sunish; Varanasi, Vijay K; Wiersma, Andrew; Westra, Philip; Stahlman, Phillip W; Gill, Bikram S

    2014-11-01

    Recent rapid evolution and spread of resistance to the most extensively used herbicide, glyphosate, is a major threat to global crop production. Genetic mechanisms by which weeds evolve resistance to herbicides largely determine the level of resistance and the rate of evolution of resistance. In a previous study, we determined that glyphosate resistance in Kochia scoparia is due to the amplification of the 5-Enolpyruvylshikimate-3-Phosphate Synthase (EPSPS) gene, the enzyme target of glyphosate. Here, we investigated the genomic organization of the amplified EPSPS copies using fluorescence in situ hybridization (FISH) and extended DNA fiber (Fiber FISH) on K. scoparia chromosomes. In both glyphosate-resistant K. scoparia populations tested (GR1 and GR2), FISH results displayed a single and prominent hybridization site of the EPSPS gene localized on the distal end of one pair of homologous metaphase chromosomes compared with a faint hybridization site in glyphosate-susceptible samples (GS1 and GS2). Fiber FISH displayed 10 copies of the EPSPS gene (approximately 5 kb) arranged in tandem configuration approximately 40 to 70 kb apart, with one copy in an inverted orientation in GR2. In agreement with FISH results, segregation of EPSPS copies followed single-locus inheritance in GR1 population. This is the first report of tandem target gene amplification conferring field-evolved herbicide resistance in weed populations. PMID:25037215

  15. A quantitative trait locus for ascites on chromosome 9 in broiler chicken lines

    PubMed Central

    Krishnamoorthy, Sriram; Smith, Candace D.; Al-Rubaye, Adnan A.; Erf, Gisela F.; Wideman, Robert F.; Anthony, Nicholas B.; Rhoads, Douglas D.

    2014-01-01

    A genome-wide SNP survey was used to identify chromosomal regions that showed linkage disequilibrium with respect to ascites susceptibility and ventricular hypertrophy in an F2 cross between previously described ascites-resistant and -susceptible lines. Variable number tandem repeats were used to obtain genotype data to further characterize these regions. A region on chromosome 9 (12 to 13 Mbp in 2011 assembly) shows association with ascites in the ascites lines and in several commercial broiler breeder lines with a significant sex effect. There are 2 candidate genes, AGTR1 (an angiotensin II type 1 receptor) and UTS2D (urotensin 2 domain containing), in this region that have been associated with hypertension and hypoxic response in mammals. PMID:24570451

  16. Linkage mapping of the locus for inherited ovine arthrogryposis (IOA) to sheep chromosome 5.

    PubMed

    Murphy, Angela M; MacHugh, David E; Park, Stephen D E; Scraggs, Erik; Haley, Chris S; Lynn, David J; Boland, Maurice P; Doherty, Michael L

    2007-01-01

    Arthrogryposis is a congenital malformation affecting the limbs of newborn animals and infants. Previous work has demonstrated that inherited ovine arthrogryposis (IOA) has an autosomal recessive mode of inheritance. Two affected homozygous recessive (art/art) Suffolk rams were used as founders for a backcross pedigree of half-sib families segregating the IOA trait. A genome scan was performed using 187 microsatellite genetic markers and all backcross animals were phenotyped at birth for the presence and severity of arthrogryposis. Pairwise LOD scores of 1.86, 1.35, and 1.32 were detected for three microsatellites, BM741, JAZ, and RM006, that are located on sheep Chr 5 (OAR5). Additional markers in the region were identified from the genetic linkage map of BTA7 and by in silico analyses of the draft bovine genome sequence, three of which were informative. Interval mapping of all autosomes produced an F value of 21.97 (p < 0.01) for a causative locus in the region of OAR5 previously flagged by pairwise linkage analysis. Inspection of the orthologous region of HSA5 highlighted a previously fine-mapped locus for human arthrogryposis multiplex congenita neurogenic type (AMCN). A survey of the HSA5 genome sequence identified plausible candidate genes for both IOA and human AMCN.

  17. A locus for cerebral cavernous malformations maps to chromosome 7q in two families

    SciTech Connect

    Marchuk, D.A.; Gallione, C.J.; Morrison, L.A.; Davis, L.E.; Clericuzio, C.L.

    1995-07-20

    Cavernous malformations (angiomas) affecting the central nervous system and retina can be inherited in autosomal dominant pattern (OMIM 116860). These vascular lesions may remain clinically silent or lead to a number of neurological symptoms including seizure, intracranial hemorrhage, focal neurological deficit, and migraine. We have mapped a gene for this disorder in two families, one of Italian-American origin and one of Mexican-American origin, to markers on proximal 7q, with a combined maximum lod score of 3.92 ({theta} of zero) with marker D7S479. Haplotype analysis of these families places the locus between markers D7S502 proximally and D7S515 distally, an interval of approximately 41 cM. The location distinguishes this disorder from an autosomal dominant vascular malformation syndrome where lesions are primarily cutaneous and that maps to 9p21. 16 refs., 3 figs., 1 tab.

  18. New susceptibility locus for NIDDM is localized to human chromosome 20q.

    PubMed

    Ji, L; Malecki, M; Warram, J H; Yang, Y; Rich, S S; Krolewski, A S

    1997-05-01

    To test the hypothesis that a gene (or genes) in the "MODY1 region" of the long arm of chromosome 20 contributes to the development of NIDDM, we conducted linkage studies in 29 extended Caucasian families in which many members were affected with NIDDM. A total of 498 individuals, including 159 NIDDM patients with an average age at diagnosis of 47 years, were genotyped for eight highly polymorphic microsatellite markers spanning a 31-cM region on chromosome 20q12-13.1. Using affected sib-pair analysis, we obtained evidence suggesting linkage between NIDDM and markers D20S119, D20S178, and D20S197 (allele sharing identical-by-descent [IBD], 0.56 for all three; P = 0.005, P = 0.009, and P = 0.004, respectively). Multipoint nonparametric linkage (NPL) analysis also showed evidence for linkage of NIDDM with the same three markers. The evidence for linkage was much stronger (allele sharing IBD by affected sibpairs, 0.64 [P < 0.0001]; maximum NPL score, 3.3 [P = 0.009]) in the 14 families whose average age at diagnosis of NIDDM was above the median (47 years) for all families. In these 14 families, one particular allele of the microsatellite D20S197 was transmitted from heterozygous parents to NIDDM offspring more frequently than expected (P < 0.01). This indicates that the marker allele and the disease allele are in linkage disequilibrium, implying that they are in close proximity. Consequently, the recently identified MODY1 gene (hepatocyte nuclear factor 4) is an unlikely candidate gene for NIDDM in our families, since it is located about 8 cM centromeric of D20S197. In conclusion, we have identified a new region on chromosome 20q that contains one or more NIDDM genes distinct from the recently identified MODY1 gene. PMID:9133558

  19. A somatic cell hybrid map of the long arm of human chromosome 17, containing the familial breast cancer locus (BRCA1)

    SciTech Connect

    Black, D.M.; Nicolai, H.; Borrow, J.; Solomon, E. )

    1993-04-01

    The authors describe a detailed somatic cell hybrid map of human chromosome 17q11.2-q23, containing the familial breast and ovarian cancer locus (BRCA1) and highly informative closely linked markers. An X-irradiation panel of 38 hamster/human and mouse/human hybrids with fragments of chromosome 17 was generated and characterized with 22 STS markers from this chromosome. A detailed map of 61 probes onto chromosome 17q, subdividing the chromosome arm into 25 regions, was done by using a panel of hybrids with well-defined breakpoints and nine chromosome-mediated gene transfectants. The localization of RARA, TOP2, EDH17BI and 2, and possibly WNT3, between THRAL and D17SI81, two markers known to flank BRCA1, suggests that any of these is a potential candidate for the BRCA1 locus. The marker D17S579 (Mfd188), which is believed to be very close to BRCAI, maps closest to the EDH17B genes. 35 refs., 1 fig., 2 tabs.

  20. Evidence of linkage of familial hypoalphalipoproteinemia to a novel locus on chromosome 11q23.

    PubMed Central

    Kort, E N; Ballinger, D G; Ding, W; Hunt, S C; Bowen, B R; Abkevich, V; Bulka, K; Campbell, B; Capener, C; Gutin, A; Harshman, K; McDermott, M; Thorne, T; Wang, H; Wardell, B; Wong, J; Hopkins, P N; Skolnick, M; Samuels, M

    2000-01-01

    Coronary heart disease (CHD) accounts for half of the 1 million deaths annually ascribed to cardiovascular disease and for almost all of the 1.5 million acute myocardial infarctions. Within families affected by early and apparently heritable CHD, dyslipidemias have a much higher prevalence than in the general population; 20%-30% of early familial CHD has been ascribed to primary hypoalphalipoproteinemia (low HDL-C). This study assesses the evidence for linkage of low HDL-C to chromosomal region 11q23 in 105 large Utah pedigrees ascertained with closely related clusters of early CHD and expanded on the basis of dyslipidemia. Linkage analysis was performed by use of 22 STRP markers in a 55-cM region of chromosome 11. Two-point analysis based on a general, dominant-phenotype model yielded LODs of 2.9 for full pedigrees and 3.5 for 167 four-generation split pedigrees. To define a localization region, model optimization was performed using the heterogeneity, multipoint LOD score (mpHLOD). This linkage defines a region on 11q23.3 that is approximately 10 cM distal to-and apparently distinct from-the ApoAI/CIII/AIV gene cluster and thus represents a putative novel localization for the low HDL-C phenotype. PMID:10775531

  1. Mapping of the bovine spinal muscular atrophy locus to Chromosome 24.

    PubMed

    Medugorac, Ivica; Kemter, Juliane; Russ, Ingolf; Pietrowski, Detlef; Nüske, Stefan; Reichenbach, Horst-Dieter; Schmahl, Wolfgang; Förster, Martin

    2003-06-01

    A hereditary form of spinal muscular atrophy (SMA) caused by an autosomal recessive gene has been reported for American Brown-Swiss cattle and in advanced backcrosses between American Brown-Swiss and many European brown cattle breeds. Bovine SMA (bovSMA) bears remarkable resemblance to the human SMA (SMA1). Affected homozygous calves also show progressive symmetric weakness and neurogenic atrophy of proximal muscles. The condition is characterized by severe muscle atrophy, quadriparesis, and sternal recumbency as result of neurogenic atrophy. We report on the localization of the gene causing bovSMA within a genomic interval between the microsatellite marker URB031 and the telomeric end of bovine Chromosome (Chr) 24 (BTA24). Linkage analysis of a complex pedigree of German Braunvieh cattle revealed a recombination fraction of 0.06 and a three-point lod score of 11.82. The results of linkage and haplotyping analysis enable a marker-assisted selection against bovSMA based on four microsatellite markers most telomeric on BTA24 to a moderate accuracy of 89-94%. So far, this region is not orthologous to any human chromosome segments responsible for twelve distinct disease phenotypes of autosomal neuropathies. Our results indicate the apoptosis-inhibiting protein BCL2 as the most promising positional candidate gene causing bovSMA. Our findings offer an attractive animal model for a better understanding of human forms of SMA and for a probable anti-apoptotic synergy of SMN-BCL2 aggregates in mammals.

  2. Meiotic stability and polymorphism of CAG repeat in normal chromosome at SCA1 locus

    SciTech Connect

    Limprasert, P.; Nouri, N.; Keats, B.J.B.

    1994-09-01

    Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder associated with an unstable and expanded CAG repeat. We analyzed the CAG repeat in normal chromosomes from various sources including SCA1 and nonSCA1 families, and Caucasian, African American, Eskimo, South American Indian and Acadian populations. The range of CAG repeats is 10-37 in normal alleles while the disease allele contains 45-65 repeats in our studies. To determine unbiased normal allelic frequencies, we analyzed data from unrelated individuals in each group. The significance of differences in allelic frequencies among the groups was determined by a chi-square test. Caucasian and Acadian frequencies were similar (p = 0.23), but highly significant differences were found among the Caucasians, African Americans, Eskimos, and South American Indians (p < 0.0005), and the range of allele sizes was much narrower in Eskimos and South American Indians. To determine if the normal chromosome is susceptible to meiotic instability, we examined members of 19 Caucasian and 24 Acadian families. Normal sized CAG repeats were faithfully transmitted from parents to offspring without any alteration in CAG number in 236 meioses. Transmission of CAG repeats in normal alleles were also stable in our SCA1 family. However, the disease allele was associated with a significant degree of instability. Some patients showed 2 expanded bands in DNA prepared from untransformed blood cells. This finding suggest mitotic instability of the disease allele.

  3. Cosmid walking and chromosome jumping in the region of PKD1 reveal a locus duplication and three CpG islands.

    PubMed Central

    Gillespie, G A; Germino, G G; Somlo, S; Weinstat-Saslow, D; Breuning, M H; Reeders, S T

    1990-01-01

    The locus responsible for the most common form of autosomal dominant polycystic kidney disease (PKD1) is located on chromosome 16p13.3. Genetic mapping studies indicate that PKD1 is flanked on the proximal side by the DNA marker 26.6 (D16S125). Here we show that 26.6 has undergone a locus duplication and that the two loci are less than 150kb apart. One of the two loci contains a polymorphic TaqI site that has been used in genetic studies and represents the proximal boundary for the PKD1 locus. We demonstrate that the polymorphic locus is the more proximal of the two 26.6-hybridizing loci. Therefore, four cosmids isolated from the distal 26.6-hybridizing locus contain candidate sequences for the PKD1 gene. These cosmids were found to contain two CpG islands that are likely markers for transcribed regions. A third CpG island was detected and cloned by directional chromosome jumping. Images PMID:1979857

  4. The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids.

    PubMed Central

    Kedda, M. A.; Stevens, G.; Manga, P.; Viljoen, C.; Jenkins, T.; Ramsay, M.

    1994-01-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid "ty-pos OCA" individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and "normal" chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8198130

  5. Juvenile myoclonic epilepsy locus in chromosome 6p21.2-p11: Linkage to convulsions and electroencephalography trait

    SciTech Connect

    Liu, A.W.; Delgado-Escueta, A.V.; Serratosa, J.M.

    1995-08-01

    Despite affecting 4 million Americans and 100-200 million persons worldwide, the precise molecular mechanisms of human epilepsies remain unknown. Juvenile myoclonic epilepsy (JME) is the most frequent and, hence, most important form of hereditary grand mal epilepsy. In this epilepsy, electroencephalographic (EEG) 15-30 Hz multispikes produce myoclonic and tonic-clonic convulsions beginning at 8-20 years of age. Moreover, EEG 3.5-6 Hz multispike wave complexes appear in clinically asymptomatic family members. We first studied 38 members of a four-generation LA-Belize family with classical JME but with no pyknoleptic absences. Five living members had JME; four clinically asymptomatic members had EEG multispike wave complexes. Pairwise analysis tightly linked microsatellites centromeric to HLA, namely D6S272 (peak lod score [Z{sub max}]=3.564-3.560 at male-female recombination [{theta}{sub m=f}]=0-0.001) and D6S257 (Z{sub max}=3.672-3.6667 at {theta}{sub m=f}=0-0.001), spanning 7 cM, to convulsive seizures and EEG multispike wave complexes. A recombination between D6S276 and D6S273 in one affected member placed the JME locus within or below HLA. Pairwise, multipoint, and recombination analyses in this large family independently proved that a JME gene is located in chromsome 6p, centromeric to HLA. We next screened, with the same chromosome 6p21.2-p11 short tandem-repeat polymorphic markers, seven multiplex pedigrees with classic JME. When lod scores for small multiplex families are added to lod scores of the LA-Belize pedigree, Z{sub max} values for D6S294 and D6S257 are >7 ({theta}{sub m=f}=0.000). Our results prove that in chromosome 6p21.2-p11 an epilepsy locus exists whose phenotype consists of classic JME with convulsions and/or EEG rapid multispike wave complexes. 31 refs., 6 figs., 4 tabs.

  6. Construction of a transcription map surrounding the BRCA1 locus of human chromosome 17

    SciTech Connect

    Brody, L.C.; Castilla, L.H.; McKinley, D.R.

    1995-01-01

    We have used a combination of methods to survey approximately 600 kb of genomic DNA surrounding the BRCA1 gene for transcribed sequences. We have cloned a set of fragments representing at least 26 genes. The DNA sequence of these clones reveals that 5 are previously cloned genes; the precise chromosomal location of 2 was previously unknown, and 3 have been cloned and mapped by others to this interval. Three other genes, including BRCA1 itself, have recently been mapped independently to this region. Sequences from 11 genes are similar but not identical matches to known genes; 5 of these appear to be the human homologues of genes cloned from other species. Another 7 genes have no similarity with known genes. In addition, 39 putative exons and 14 expressed sequence tags have been identified and mapped to individual cosmids. This transcript map provides a detailed description of gene organization for this region of the genome. 64 refs., 4 figs., 1 tab.

  7. Autozygosity Mapping of a Seckel Syndrome Locus to Chromosome 3q22.1-q24

    PubMed Central

    Goodship, Judith; Gill, Harinder; Carter, Joan; Jackson, Andrew; Splitt, Miranda; Wright, Michael

    2000-01-01

    Seckel syndrome (MIM 210600) is an autosomal recessive disorder of low birth weight, severe microcephaly, and dysmorphic facial appearance with receding forehead, prominent nose, and micrognathia. We have performed a genomic screen in two consanguineous families of Pakistani origin and found that the disorder segregates with markers between loci D3S1316 and D3S3710, which map to chromosome 3q22.1-q24. Analysis using HOMOZ/MAPMAKER gave a maximum LOD score of 8.72. All five affected individuals were homozygous for the same allele, for two adjacent polymorphic markers within the region segregating with the disease, narrowing the region to 12 cM. PMID:10889046

  8. Family-based association analysis of 42 hereditary prostate cancer families identifies the Apolipoprotein L3 region on chromosome 22q12 as a risk locus.

    PubMed

    Johanneson, Bo; McDonnell, Shannon K; Karyadi, Danielle M; Quignon, Pascale; McIntosh, Laura; Riska, Shaun M; FitzGerald, Liesel M; Johnson, Gregory; Deutsch, Kerry; Williams, Gabrielle; Tillmans, Lori S; Stanford, Janet L; Schaid, Daniel J; Thibodeau, Stephen N; Ostrander, Elaine A

    2010-10-01

    Multiple genome-wide scans for hereditary prostate cancer (HPC) have identified susceptibility loci on nearly every chromosome. However, few results have been replicated with statistical significance. One exception is chromosome 22q, for which five independent linkage studies yielded strong evidence for a susceptibility locus in HPC families. Previously, we refined this region to a 2.53 Mb interval, using recombination mapping in 42 linked pedigrees. We now refine this locus to a 15 kb interval, spanning Apolipoprotein L3 (APOL3), using family-based association analyses of 150 total prostate cancer (PC) cases from two independent family collections with 506 unrelated population controls. Analysis of the two independent sets of PC cases highlighted single nucleotide polymorphisms (SNPs) within the APOL3 locus showing the strongest associations with HPC risk, with the most robust results observed when all 150 cases were combined. Analysis of 15 tagSNPs across the 5' end of the locus identified six SNPs with P-values < or =2 × 10(-4). The two independent sets of HPC cases highlight the same 15 kb interval at the 5' end of the APOL3 gene and provide strong evidence that SNPs within this 15 kb interval, or in strong linkage disequilibrium with it, contribute to HPC risk. Further analyses of this locus in an independent population-based, case-control study revealed an association between an SNP within the APOL3 locus and PC risk, which was not confirmed in the Cancer Genetic Markers of Susceptibility data set. This study further characterizes the 22q locus in HPC risk and suggests that the role of this region in sporadic PC warrants additional studies.

  9. Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight.

    PubMed

    Park, Mi-Hyun; Kwak, Soo Heon; Kim, Kwang Joong; Go, Min Jin; Lee, Hye-Ja; Kim, Kyung-Seon; Hwang, Joo-Yeon; Kimm, Kuchan; Cho, Young-Min; Lee, Hong Kyu; Park, Kyong Soo; Lee, Jong-Young

    2013-02-08

    The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candidate genes within linkage regions to identify genetic variants that predispose individuals to being overweight and developing type 2 diabetes. Through fine-mapping analysis of chromosome 4q34-35, we detected a locus potentially linked (nonparametric linkage 2.81, logarithm of odds 2.27, P=6×10(-4)) to type 2 diabetes in overweight or obese individuals (body mass index, BMI≥23 kg m(-2)). Multiple regression analysis with type 2 diabetes-related phenotypes revealed a significant association (false discovery rate (FDR) P=0.006 for rs13144140; FDR P=0.002 for rs6830266) between GPM6A (rs13144140) and BMI and waist-hip ratio, and between NEIL3 (rs6830266) and insulin level from 1314 normal individuals. Our systematic search of genome-wide linkage and association studies, demonstrate that a linkage peak for type 2 diabetes on chromosome 4q34-35 contains two type 2 diabetes-related genes, GPM6A and NEIL3.

  10. Development of isohomoeoallelic lines within the wheat cv. Courtot for high molecular weight glutenin subunits: transfer of the Glu-D1 locus to chromosome 1A.

    PubMed

    Dumur, J; Branlard, G; Tanguy, A-M; Dardevet, M; Coriton, O; Huteau, V; Lemoine, J; Jahier, Joseph

    2009-08-01

    Wheat quality depends on protein composition and grain protein content. High molecular weight glutenin subunits (HMW-GS) play an important role in determining the viscoelastic properties of gluten. In an attempt to improve the bread-making quality of hexaploid wheat by elaborating novel HMW-GS combinations, a fragment of wheat chromosome 1D containing the Glu-D1 locus encoding the Dx2+Dy12 subunits was translocated to the long arm of chromosome 1A using the ph1b mutation. The partially isohomoeoallelic line selected was characterized using cytogenetical and molecular approaches to assess the amount of chromatin introgressed in the translocated 1A chromosome. Triple-target genomic in situ hybridization indicated that the translocated 1A chromosome had a terminal 1D segment representing 25% of the length of the recombinant long arm. The translocation was also identified on the long arm using molecular markers, and its length was estimated with a minimum of 91 cM. Proteome analysis was performed on total endosperm proteins. Out of the 152 major spots detected, 9 spots were up-regulated and 4 spots were down-regulated. Most of these proteins were identified as alpha-, beta-, gamma-gliadins assigned to the chromosomes of homoeologous groups 1 and 6. Quantitative variations in the HMW-GS were only observed in subunit Dy12 in response to duplication of the Glu-D1 locus.

  11. Evidence for a chromosome 22q susceptibility locus for some schizophrenics

    SciTech Connect

    Pulver, A.E.; Wolyniec, P.; Nestadt, G.

    1994-09-01

    Recent reports from linkage studies suggests that in some families there may be a gene associated with schizophrenia on chromosome 22q. Given the probable heterogeneity of schizophrenia, further exploration of this region was undertaken. The region was examined for candidate genes and diseases reported to have some psychiatric manifestations. Studies were initiated to examine the the potential phenotypic and molecular similarity between schizophrenia and velo-cardio-facial syndrome (VCFS), a syndrome associated with an interstitial deletion of 22q11.2. Phenotypic expression: (1) psychiatric evaluations of VCFS patients and their relatives found a high rate of DSM III-R schizophrenia in the patients and of psychotic illness in their 2nd and 3rd degree relatives. (2) 160 schizophrenic patients from the Maryland Epidemiology Sample (MES) were evaluated for the presence of typical facies seen in VCFS. Rating a 5-point scale, {open_quotes}5{close_quotes} being most likely, 15 (9.4%) were rated {open_quotes}5{close_quotes} and 27 (16.9%) were rated {open_quotes}4{close_quotes} for the VCFS-like facial features. Molecular characteristics: fluorescent in situ hybridization methods (FISH) identified 3 schizophrenics among 60 in the MES with the microdeletion of probe sc11.lab commonly deleted in VCFS subjects. This work provides a model for the mapping of complex phenotypes such schizophrenia using both genetic and epidemiological methods.

  12. Chromosomal locus tracking with proper accounting of static and dynamic errors.

    PubMed

    Backlund, Mikael P; Joyner, Ryan; Moerner, W E

    2015-06-01

    The mean-squared displacement (MSD) and velocity autocorrelation (VAC) of tracked single particles or molecules are ubiquitous metrics for extracting parameters that describe the object's motion, but they are both corrupted by experimental errors that hinder the quantitative extraction of underlying parameters. For the simple case of pure Brownian motion, the effects of localization error due to photon statistics ("static error") and motion blur due to finite exposure time ("dynamic error") on the MSD and VAC are already routinely treated. However, particles moving through complex environments such as cells, nuclei, or polymers often exhibit anomalous diffusion, for which the effects of these errors are less often sufficiently treated. We present data from tracked chromosomal loci in yeast that demonstrate the necessity of properly accounting for both static and dynamic error in the context of an anomalous diffusion that is consistent with a fractional Brownian motion (FBM). We compare these data to analytical forms of the expected values of the MSD and VAC for a general FBM in the presence of these errors.

  13. Chromosomal locus tracking with proper accounting of static and dynamic errors

    NASA Astrophysics Data System (ADS)

    Backlund, Mikael P.; Joyner, Ryan; Moerner, W. E.

    2015-06-01

    The mean-squared displacement (MSD) and velocity autocorrelation (VAC) of tracked single particles or molecules are ubiquitous metrics for extracting parameters that describe the object's motion, but they are both corrupted by experimental errors that hinder the quantitative extraction of underlying parameters. For the simple case of pure Brownian motion, the effects of localization error due to photon statistics ("static error") and motion blur due to finite exposure time ("dynamic error") on the MSD and VAC are already routinely treated. However, particles moving through complex environments such as cells, nuclei, or polymers often exhibit anomalous diffusion, for which the effects of these errors are less often sufficiently treated. We present data from tracked chromosomal loci in yeast that demonstrate the necessity of properly accounting for both static and dynamic error in the context of an anomalous diffusion that is consistent with a fractional Brownian motion (FBM). We compare these data to analytical forms of the expected values of the MSD and VAC for a general FBM in the presence of these errors.

  14. Chromosomal locus tracking with proper accounting of static and dynamic errors

    PubMed Central

    Backlund, Mikael P.; Joyner, Ryan; Moerner, W. E.

    2015-01-01

    The mean-squared displacement (MSD) and velocity autocorrelation (VAC) of tracked single particles or molecules are ubiquitous metrics for extracting parameters that describe the object’s motion, but they are both corrupted by experimental errors that hinder the quantitative extraction of underlying parameters. For the simple case of pure Brownian motion, the effects of localization error due to photon statistics (“static error”) and motion blur due to finite exposure time (“dynamic error”) on the MSD and VAC are already routinely treated. However, particles moving through complex environments such as cells, nuclei, or polymers often exhibit anomalous diffusion, for which the effects of these errors are less often sufficiently treated. We present data from tracked chromosomal loci in yeast that demonstrate the necessity of properly accounting for both static and dynamic error in the context of an anomalous diffusion that is consistent with a fractional Brownian motion (FBM). We compare these data to analytical forms of the expected values of the MSD and VAC for a general FBM in the presence of these errors. PMID:26172745

  15. Disruption of chromosomal locus 1p36 differentially modulates TAp73 and ΔNp73 expression in follicular lymphoma

    PubMed Central

    Hassan, Hesham M.; Varney, Michelle L.; Jain, Smrati; Weisenburger, Dennis D.; Singh, Rakesh K.; Dave, Bhavana J.

    2015-01-01

    The TP73 gene is located at the chromosome 1p36 locus that is commonly disrupted or deleted in follicular lymphoma (FL) with poor prognosis. Therefore, we analyzed the expression of the pro-apoptotic TAp73 and anti-apoptotic ΔNp73 isoforms in FL cases with normal or abnormal 1p36. We observed a significant increase in ΔNp73 expression and ΔNp73:TAp73 ratio, lower expression of cleaved caspase-3 and a higher frequency of Ki-67 and PCNA positive cells in FL cases with abnormal 1p36. A negative correlation between the ΔNp73:TAp73 ratio and cleaved caspase-3 expression, and a positive correlation between ΔNp73 expression and Ki-67 or PCNA were observed. The expression of TAp73 and its pro-apoptotic transcriptional targets Bim, Puma, and Noxa were significantly lower in FL compared to reactive follicular hyperplasia. Together, our data demonstrates that 1p36 disruption is associated with increased ΔNp73 expression, decreased apoptosis and increased proliferation in FL. PMID:24660851

  16. Disruption of chromosomal locus 1p36 differentially modulates TAp73 and ΔNp73 expression in follicular lymphoma.

    PubMed

    Hassan, Hesham M; Varney, Michelle L; Jain, Smrati; Weisenburger, Dennis D; Singh, Rakesh K; Dave, Bhavana J

    2014-12-01

    The TP73 gene is located at the chromosome 1p36 locus that is commonly disrupted or deleted in follicular lymphoma (FL) with poor prognosis. Therefore, we analyzed the expression of the pro-apoptotic TAp73 and anti-apoptotic ΔNp73 isoforms in cases of FL with normal or abnormal 1p36. We observed a significant increase in ΔNp73 expression and ΔNp73:TAp73 ratio, lower expression of cleaved caspase-3 and a higher frequency of Ki-67 and proliferating cell nuclear antigen (PCNA) positive cells in cases of FL with abnormal 1p36. A negative correlation between the ΔNp73:TAp73 ratio and cleaved caspase-3 expression, and a positive correlation between ΔNp73 expression and Ki-67 or PCNA, were observed. The expression of TAp73 and its pro-apoptotic transcriptional targets BIM. PUMA and NOXA were significantly lower in FL compared to reactive follicular hyperplasia. Together, our data demonstrate that 1p36 disruption is associated with increased ΔNp73 expression, decreased apoptosis and increased proliferation in FL.

  17. Human cardiac troponin T: Identification of fetal isoforms and assignment of the TNNT2 locus to chromosome 1q

    SciTech Connect

    Townsend, P.J.; Farza, H.; Yacoub, M.H.; Barton, P.J.R. ); MacGeoch, C.; Spurr, N.K. ); Wade, R. ); Gahlmann, R. )

    1994-05-15

    The troponin complex is located on the thin filament of striated muscle and is composed of three component polypeptides: Troponin T, troponin I, and troponin C. Three troponin T genes have been described on the basis of molecular cloning in humans and other vertebrates. These are expressed in a tissue-specific manner and encode the troponin T isoforms expressed in cardiac muscle, slow skeletal muscle, and fast skeletal muscle, respectively. Each of these genes is subject to alternative splicing, resulting in the production of multiple tissue-specific isoforms. The authors have cloned cDNAs encoding human cardiac troponin T from adult heart and have used these to demonstrate that multiple cardiac troponin T mRNAs are present in the human fetal heart, resulting from alternative splicing in the 5[prime] coding region of the gene. Hybridization of the cloned cDNAs to genomic DNA identifies a single-copy gene, and using somatic cell hybrid analysis, the authors have mapped the corresponding gene locus (designated TNNT2) to the long arm of chromosome 1 (1cen-qter). 52 refs., 2 figs., 1 tab.

  18. Genetic mapping of the cleidocranial dysplasia (CCD) locus on chromosome band 6p21 to include a microdeletion

    SciTech Connect

    Gelb, B.D.; Desnick, R.J.; Shevell, M.

    1995-08-28

    Cleidocranial dysplasia (CCD) is a generalized skeletal dysplasia with autosomal dominant inheritance. Recently, the CCD disease locus was localized to 23 and 17 cM regions of chromosome band 6p21 by linkage studies of seven affected families. Of note, the 23 cM region contained a microdeletion detected in one family at D6S459, an interval that was excluded in the 17 cM overlapping region. Here, linkage of CCD to 6p21 was independently confirmed with a maximal two-point LOD score of Z=5.12 with marker D6S452 at {theta}=0.00. Recombinant events in two affected individuals defined a CCD region of 7 cM from D6S465 to D6S282, which overlapped with the CCD region containing the microdeletion but did not overlap with the 17 cM critical region from D6S282 to D6S291. These results suggest the refined localization of the CCD region to 6 cM spanning markers D6S438 to D6S282, thereby reviving the possibility that the CCD gene lies within the microdeletion at D6S459. 13 refs., 2 figs., 1 tab.

  19. Fine mapping and haplotype analysis of the locus for congenital nephrotic syndrome on chromosome 19q13.1

    SciTech Connect

    Maennikkoe, M.; Kestilae, M.; Tryggvason, K.

    1995-12-01

    We have recently localized the gene for congenital nephrotic syndrome of the Finnish type (CNF) to chromosome 19q12-13.1. On the basis of observed recombination events, the gene was localized between markers D19S416/D19S425/D19S213/D19S208/D19S191 and D19S224. Here we have extended the mapping efforts, on the basis of a detailed physical map of the region. By means of three new polymorphic markers - D19S608, D19S609, and D19S610 - developed in this study, the critical candidate region could be further restricted. Significant linkage disequilibrium was observed with marker D19S610, D19S608, D19S224, and D19S220, the strongest allelic association being 84% with marker D19S610 at 19q13.1. This suggests that the CNF gene locus lies in close proximity to marker D19S610. Combination of the informative markers revealed four main haplotype categories. Different geographic distribution was observed between these haplotype groups when they were placed on the map of Finland according to the birthplaces of grandparents. 38 refs., 2 figs., 4 tabs.

  20. Identification of the locus for human polymorphic cataract on chromosome 2 near gamma-crystallin gene cluster

    SciTech Connect

    Rogaev, E.I.; Rogaeva, E.A.; Keryanov, S.

    1994-09-01

    Cataract is the leading cause of blindness in human population. While positive linkage data have been obtained for some forms of inherited cataract, no evidence for mutations in any genes have been reported for human inherited cataract existing as an isolated abnormality. Previously, we have described the autosomal dominant polymorphic congenital cataract (PCC) which is characterized by partial opacity located between the fetal nucleus of the lens and the equator. The number, color and form of opacity is varied. We described pedigrees with 73 affected individuals, and used this in a linkage analysis with a set of polymorphic DNA markers randomly placed across the genome as well as with markers selected from some of the candidate genes or from nearby chromosomal regions. We have found evidence for segregation of a cataract locus with DNA markers from 2q36. The causative genetic defect has been mapped to a 20 cM interval which includes a cluster of gamma-crystallin genes. The gamma-crystallin proteins are abundant soluble low molecular weight proteins in the lens. We have used the trinucleotide repeat polymorphic markers from intron 2 of gamma-crystallin B gene and found the segregation of this marker with the disease with no evidence for recombination in the pedigree containing 62 affected individuals. These data suggest that the non-nuclear forms of human cataract may be caused by defects in gamma-crystallin genes.

  1. Identification of a locus on mouse chromosome 3 involved in differential susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease.

    PubMed Central

    Melvold, R W; Jokinen, D M; Miller, S D; Dal Canto, M C; Lipton, H L

    1990-01-01

    Theiler's virus-induced demyelinating disease results from a chronic infection in the white matter of the central nervous system and provides an excellent model for human multiple sclerosis. Like multiple sclerosis, there are genetic risk factors in disease development, including genes associated with the major histocompatibility complex and with those encoding the beta chain of the T-cell receptor. Comparisons of the susceptible DBA/2 and resistant C57BL/6 strains have indicated an important role for the H-2D locus and for a non-H-2 gene (not involving the beta chain of the T-cell receptor) in differential susceptibility. In the present report, analysis of recombinant-inbred strains (BXD) between the DBA/2 and C57BL/6 strains indicated that this non-H-2 locus is located at the centromeric end of chromosome 3 near (4 +/- 4 centimorgans) the carbonic anhydrase-2 (Car-2) enzyme locus. PMID:2296080

  2. Genomic association analysis suggests chromosome 12 locus influencing antihypertensive response to thiazide diuretic.

    PubMed

    Turner, Stephen T; Bailey, Kent R; Fridley, Brooke L; Chapman, Arlene B; Schwartz, Gary L; Chai, High Seng; Sicotte, Hugues; Kocher, Jean-Pierre; Rodin, Andréi S; Boerwinkle, Eric

    2008-08-01

    We conducted a genome-wide association study to identify novel genes influencing diastolic blood pressure (BP) response to hydrochlorothiazide, a commonly prescribed thiazide diuretic preferred for the treatment of high BP. Affymetrix GeneChip Human Mapping 100K Arrays were used to measure single nucleotide polymorphisms across the 22 autosomes in 194 non-Hispanic black subjects and 195 non-Hispanic white subjects with essential hypertension selected from opposite tertiles of the race- and sex-specific distributions of age-adjusted diastolic BP response to hydrochlorothiazide (25 mg daily, PO, for 4 weeks). The black sample consisted of 97 "good" responders (diastolic BP response [mean+/-SD]=-18.3+/-4.2 mm Hg; age=47.1+/-6.1 years; 51.5% women) and 97 "poor" responders (diastolic BP response=-0.18+/-4.3; age=47.4+/-6.5 years; 51.5% women). Haplotype trend regression identified a region of chromosome 12q15 in which haplotypes constructed from 3 successive single nucleotide polymorphisms (rs317689, rs315135, and rs7297610) in proximity to lysozyme (LYZ), YEATS domain containing 4 (YEATS4), and fibroblast growth receptor substrate 2 (FRS2) were significantly associated with diastolic BP response (nominal P=2.39 x 10(-7); Bonferroni corrected P=0.024; simulated experiment-wise P=0.040). Genotyping of 35 additional single nucleotide polymorphisms selected to "tag" linkage disequilibrium blocks in these genes provided corroboration that variation in LYZ and YEATS4 was associated with diastolic BP response in a statistically independent data set of 291 black subjects and in the sample of 294 white subjects. These results support the use of genome-wide association analyses to identify novel genes influencing antihypertensive drug responses. PMID:18591461

  3. A putative quantitative trait locus on chromosome 20 associated with bovine pathogenic disease incidence.

    PubMed

    Casas, E; Snowder, G D

    2008-10-01

    The objective of this study was to detect QTL associated with the incidence of multiple pathogenic diseases in offspring from half-sib bovine families. Four F(1) sires were used to produce offspring: Brahman x Hereford (BH; n = 547), Piedmontese x Angus (PA; n = 209), Brahman x Angus (n = 176), and Belgian Blue x MARC III (n = 246). Treatment records for bovine respiratory disease, infectious keratoconjunctivitis (pinkeye), and infectious pododermatitis (footrot) were available for all of the offspring from birth to slaughter. The incidences of these 3 microbial pathogenic diseases were combined into a single binary trait to represent an overall pathogenic disease incidence. Offspring diagnosed and treated for 1 or more of the previously mentioned pathogenic diseases were coded as a 1 for affected. Cattle with no treatment record were coded as 0 for healthy. A putative QTL for pathogenic disease incidence was detected in the family derived from the BH sire at the genome-wise suggestive level. This was supported by evidence, in the same chromosomal region, of a similar QTL in the family derived from the PA sire. The maximum F-statistic (F = 13.52; P = 0.0003) was located at cM 18. The support interval of the QTL spanned from cM 9 to 28. Further studies should explore this QTL by using other bovine populations to further confirm the QTL and refine the QTL support interval. Offspring inheriting the Hereford allele, in the family from the BH sire, and the Angus allele, in the family from the PA sire, were less susceptible to incidence of pathogenic diseases, when compared with those inheriting the Brahman allele and Piedmontese allele, from the BH and PA sires, respectively. PMID:18502878

  4. Multisite haplotype on cattle chromosome 3 is associated with quantitative trait locus effects on lactation traits.

    PubMed

    Cohen-Zinder, Miri; Donthu, Ravikiran; Larkin, Denis M; Kumar, Charu Gupta; Rodriguez-Zas, Sandra L; Andropolis, Kalista E; Oliveira, Rosane; Lewin, Harris A

    2011-11-01

    The goal of this study was to identify candidate genes and DNA polymorphisms for quantitative trait loci (QTL) affecting milk yield (MY), fat yield (FY), and protein yield (PY) previously mapped to bovine chromosome 3 (BTA3). To accomplish this, 373 half-siblings sired by three bulls previously shown to be segregating for lactation trait QTL, and 263 additional sires in the U.S. Dairy Bull DNA Repository (DBDR) were genotyped for 2,500 SNPs within a 16.3 Mbp QTL critical region on BTA3. Targeted resequencing of ∼1.8 Mbp within the QTL critical region of one of the QTL heterozygous sires identified additional polymorphisms useful for association studies. Twenty-three single nucleotide polymorphisms (SNPs) within a fine-mapped region were associated with effects on breeding values for MY, FY, or PY in DBDR sires, of which five SNPs were in strong linkage disequilibrium in the population. This multisite haplotype included SNPs located within exons or promoters of four tightly linked genes: RAP1A, ADORA3, OVGP1, and C3H1orf88. An SNP within RAP1A showed strong evidence of a recent selective sweep based on integrated haplotype score and was also associated with breeding value for PY. Because of its known function in alveolar lumen formation in the mammary gland, RAP1A is thus a strong candidate gene for QTL effects on lactation traits. Our results provide a detailed assessment of a QTL region that will be a useful guide for complex traits analysis in humans and other noninbred species.

  5. Spontaneous isolated superior mesenteric artery dissection: genetic heterogeneity of chromosome locus 5q13-14 in 2 male familial cases.

    PubMed

    Jia, Zhongzhi; Zhang, Xiaoping; Wang, Weiping; Tian, Feng; Jiang, Guomin; Li, Maoquan

    2015-07-01

    Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare disease that occurs sporadically. In this report, we describe 2 cases of SISMAD involving an uncle and his nephew. Genetic studies revealed the presence of heterogeneity of a chromosome locus at 5q13-14 in 3 family members (the 2 patients and the nephew's mother), an area previously found to be linked to familial ascending aortic aneurysms and dissections.

  6. Genetic recombination events which position the Friedreich ataxia locus proximal to the D9S15/D9S5 linkage group on chromosome 9q

    SciTech Connect

    Chamberlain, S.; Shaw, J.; Wilkes, D.; Carvajal, J.; Hillerman, R.; Doudney, K.; Williamson, R. ); Farrall, M. ); Harding, A.E. ); Sirugo, G.; Fujita, R.; Koenig, M.; Mandel, J.L. ); Palau, F.; Monros, E.; Vilchez, J.; Prieto, F. ); Richter, A.; Vanasse, M.; Melancon, S. ); Cocozza, S.; Cavalcanti, F.; Pianese, L.; Filla, A. ); Redolfi, E.; DiDonato, S.; Pandolfo, M. )

    1993-01-01

    The absence of recombination between the mutation causing Friedreich ataxia and the two loci which originally assigned the disease locus to chromosome 9 has slowed attempts to isolate and characterize the genetic defect underlying this neurodegenerative disorder. A proximity of less than 1 cM to the linkage group has been proved by the generation of high maximal lod score (Z) to each of the two tightly linked markers D9S15 (Z = 96.69; recombination fraction [[theta

  7. Recovery of probes linked to the jcpk locus on mouse chromosome 10 by the use of an improved representational difference analysis technique

    SciTech Connect

    Baldocchi, R.A.; Tartaglia, K.E.; Bryda, E.C.; Flaherty, L.

    1996-04-15

    Representational difference analysis (RDA) is a subtractive hybridization technique by which the differences two complex genomes can be isolated. An improved version of this technique was used to isolate DNA segments that map to a narrow genetic region adjacent to the jcpk locus on Chromosome 10 of the mouse. A mutation at this locus acts recessively and causes an early onset polycystic kidney disease. Genomic subtractions involving DNA from C57BL/6 (B6) and its partially congenic partner, B6-jcpk/jcpk, produced 39 restriction fragments (difference products), 25 of which were unique and represented differences in BglII sites between these two strains. Although none identified the jcpk locus itself, 7 of these were mapped to an interval between 3.4 and 6.5 cM distal to the jcpk locus. Five of these 7 difference products were developed by subtracting B6-jcpk/jcpk from B6 DNA, but only 1 of the 5 was isolated using the an improved technique. The other 4 were obtained by an improved technique that included size selection of difference products after the third round of subtractive hybridization and amplification. The remaining 2 of the mapped products resulted from the reciprocal subtraction experiment using the improvements. Thus, by this improved technique and two-way subtraction, we were able to add seven new markers to a relatively small genetic region on Chromosome 10. 14 refs., 4 figs.

  8. The First Genomewide Interaction and Locus-Heterogeneity Linkage Scan in Bipolar Affective Disorder: Strong Evidence of Epistatic Effects between Loci on Chromosomes 2q and 6q

    PubMed Central

    Abou Jamra, Rami ; Fuerst, Robert ; Kaneva, Radka ; Orozco Diaz, Guillermo ; Rivas, Fabio ; Mayoral, Fermin ; Gay, Eudoxia ; Sans, Sebastian ; González, Maria Jose ; Gil, Susana ; Cabaleiro, Francisco ; del Rio, Francisco ; Perez, Fermin ; Haro, Jesus ; Auburger, Georg ; Milanova, Vihra ; Kostov, Christian ; Chorbov, Vesselin ; Stoyanova, Vessela ; Nikolova-Hill, Amelia ; Onchev, George ; Kremensky, Ivo ; Jablensky, Assen ; Schulze, Thomas G. ; Propping, Peter ; Rietschel, Marcella ; Nöthen, Markus M. ; Cichon, Sven ; Wienker, Thomas F. ; Schumacher, Johannes 

    2007-01-01

    We present the first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder (BPAD), using a large linkage data set (52 families of European descent; 448 participants and 259 affected individuals). Our results provide the strongest interaction evidence between BPAD genes on chromosomes 2q22-q24 and 6q23-q24, which was observed symmetrically in both directions (nonparametric LOD [NPL] scores of 7.55 on 2q and 7.63 on 6q; P<.0001 and P=.0001, respectively, after a genomewide permutation procedure). The second-best BPAD interaction evidence was observed between chromosomes 2q22-q24 and 15q26. Here, we also observed a symmetrical interaction (NPL scores of 6.26 on 2q and 4.59 on 15q; P=.0057 and .0022, respectively). We covered the implicated regions by genotyping additional marker sets and performed a detailed interaction linkage analysis, which narrowed the susceptibility intervals. Although the heterogeneity analysis produced less impressive results (highest NPL score of 3.32) and a less consistent picture, we achieved evidence of locus heterogeneity at chromosomes 2q, 6p, 11p, 13q, and 22q, which was supported by adjacent markers within each region and by previously reported BPAD linkage findings. Our results provide systematic insights in the framework of BPAD epistasis and locus heterogeneity, which should facilitate gene identification by the use of more-comprehensive cloning strategies. PMID:17924339

  9. Association of the IL-10 Gene Family Locus on Chromosome 1 with Juvenile Idiopathic Arthritis (JIA)

    PubMed Central

    Hamaoui, Raja; Bryant, Annette; Hinks, Anne; Ursu, Simona; Wedderburn, Lucy R.; Thomson, Wendy; Lewis, Cathryn M.; Woo, Patricia

    2012-01-01

    Background The cytokine IL-10 and its family members have been implicated in autoimmune diseases and we have previously reported that genetic variants in IL-10 were associated with a rare group of diseases called juvenile idiopathic arthritis (JIA). The aim of this study was to fine map genetic variants within the IL-10 cytokine family cluster on chromosome 1 using linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (tSNPs) approach with imputation and conditional analysis to test for disease associations. Methodology/Principal Findings Fifty-three tSNPs were tested for association between Caucasian paediatric cohorts [219 systemic JIA (sJIA), 187 persistent oligoarticular JIA (pOJIA), and 139 extended OJIA (eOJIA) patients], and controls (Wellcome Trust control cohort, WTCCC2). Significant association with sJIA was detected at rs1400986 in the promoter of IL-20 (odds ratio 1.53; 95% CI 1.21–1.93; p = 0.0004), but in no other subtypes. Imputation analysis identified additional associated SNPs for pOJIA at IL-20 and IL-24, including a rare, functional, missense variant at IL-24 with a p = 0.0002. Penalised logistic regression analysis with HyperLasso and conditional analysis identified several further associations with JIA subtypes. In particular, haplotype analysis refined the sJIA association, with a joint effect at rs1400986 and rs4129024 in intron 1 of MAPKAPK2 (p = 3.2E−5). For pOJIA, a 3-SNP haplotype including rs1878672 in intron 3 of IL-10 showed evidence for association (p = 0.0018). In eOJIA, rs10863962 (3′UTR of FCAMR) and rs12409577 (intron of IL-19) haplotype showed some evidence of association (p = 0.0003). Conclusions This study supports previous association of IL-20 with sJIA. Haplotype analyses provided stronger association signals than single point analyses, while a penalised logistic regression approach also suggested multiple independent association signals. Replication studies are required to confirm or

  10. A paracentric inversion suppresses genetic recombination at the FON3 locus with breakpoints corresponding to sequence gaps on rice chromosome 11L.

    PubMed

    Jiang, Li; Zhang, Wenli; Xia, Zhihui; Jiang, Guanghuai; Qian, Qian; Li, Aili; Cheng, Zhukuan; Zhu, Lihuang; Mao, Long; Zhai, Wenxue

    2007-03-01

    Paracentric inversion is known to inhibit genetic recombination between normal and inverted chromosomal segments in heterozygous arrangements. Insect inversion polymorphisms have been studied to reveal adaptive processes for maintaining genetic variation. We report the first paracentric inversion in rice (Oryza sativa), which was discovered in our effort to clone the floral organ number gene FON3. Recombination at the FON3 locus on the long arm of chromosome 11 was severely suppressed over a distance of more than 36 cM. An extensive screening among 8,242 F(2) progeny failed to detect any recombinants. Cytological analysis revealed a loop-like structure on pachytene chromosomes, whereas FISH analysis showed the migration of a BAC clone from a distal location to a position closer to the centromere. Interestingly, the locations where the genetic recombination suppression began were coincided with the positions of two physical gaps on the chromosome 11, suggesting a correlation between the physical gaps, the inversion breakpoints. Transposons and retrotransposons, and tandemly arranged members of gene families were among the sequences immediately flanking the gaps. Taken together, we propose that the genetic suppression at the FON3 locus was caused by a paracentric inversion. The possible genetic mechanism causing such a spontaneous inversion was proposed.

  11. Clustered cadherin genes: a sequence-ready contig for the desmosomal cadherin locus on human chromosome 18.

    PubMed

    Hunt, D M; Sahota, V K; Taylor, K; Simrak, D; Hornigold, N; Arnemann, J; Wolfe, J; Buxton, R S

    1999-12-15

    We describe the assembly of a cosmid and PAC contig of approximately 700 kb on human chromosome 18q12 spanning the DSC and DSG genes coding for the desmocollins and desmogleins. These are members of the cadherin superfamily of calcium-dependent cell adhesion proteins present in the desmosome type of cell junction found especially in epithelial cells. They provide the strong cell-cell adhesion generated by this type of cell junction for which expression of both a desmocollin and a desmoglein is required. In the autoimmune skin diseases pemphigus foliaceous and pemphigus vulgaris (PV), where the autoantigens are, respectively, encoded by the DSG1 and DSG3 genes, severe areas of acantholysis (cell separation), potentially life-threatening in the case of PV, are evident. Dominant mutations in the DSG1 gene causing striate palmoplantar keratoderma result in hyperkeratosis of the skin on the parts of the body where pressure and abrasion are greatest, viz., on the palms and soles. These genes are also candidate tumor suppressor genes in squamous cell carcinomas and other epithelial cancers. We have screened two chromosome 18-specific cosmid libraries by hybridization with previously isolated YAC clones and DSC and DSG cDNAs, and a whole genome PAC library, both by hybridization with the YACs and by screening by PCR using cDNA sequences and YAC end sequence. The contigs were extended by further PCR screens using STSs generated by vectorette walking from the ends of the cosmids and PACs, together with sequence from PAC ends. Despite screening of two libraries, the cosmid contig still had four gaps. The PAC contig filled these gaps and in fact covered the whole locus. The positions of 45 STSs covering the whole of this region are presented. The desmocollin and desmoglein genes, which are about 30-35 kb in size, are quite well separated at approximately 20-30 kb apart and are arranged in two clusters, one DSC cluster and one DSG cluster, which are transcribed outward from the

  12. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.

    PubMed

    Jacquemont, Sébastien; Reymond, Alexandre; Zufferey, Flore; Harewood, Louise; Walters, Robin G; Kutalik, Zoltán; Martinet, Danielle; Shen, Yiping; Valsesia, Armand; Beckmann, Noam D; Thorleifsson, Gudmar; Belfiore, Marco; Bouquillon, Sonia; Campion, Dominique; de Leeuw, Nicole; de Vries, Bert B A; Esko, Tõnu; Fernandez, Bridget A; Fernández-Aranda, Fernando; Fernández-Real, José Manuel; Gratacòs, Mònica; Guilmatre, Audrey; Hoyer, Juliane; Jarvelin, Marjo-Riitta; Kooy, R Frank; Kurg, Ants; Le Caignec, Cédric; Männik, Katrin; Platt, Orah S; Sanlaville, Damien; Van Haelst, Mieke M; Villatoro Gomez, Sergi; Walha, Faida; Wu, Bai-Lin; Yu, Yongguo; Aboura, Azzedine; Addor, Marie-Claude; Alembik, Yves; Antonarakis, Stylianos E; Arveiler, Benoît; Barth, Magalie; Bednarek, Nathalie; Béna, Frédérique; Bergmann, Sven; Beri, Mylène; Bernardini, Laura; Blaumeiser, Bettina; Bonneau, Dominique; Bottani, Armand; Boute, Odile; Brunner, Han G; Cailley, Dorothée; Callier, Patrick; Chiesa, Jean; Chrast, Jacqueline; Coin, Lachlan; Coutton, Charles; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; David, Albert; de Freminville, Bénédicte; Delobel, Bruno; Delrue, Marie-Ange; Demeer, Bénédicte; Descamps, Dominique; Didelot, Gérard; Dieterich, Klaus; Disciglio, Vittoria; Doco-Fenzy, Martine; Drunat, Séverine; Duban-Bedu, Bénédicte; Dubourg, Christèle; El-Sayed Moustafa, Julia S; Elliott, Paul; Faas, Brigitte H W; Faivre, Laurence; Faudet, Anne; Fellmann, Florence; Ferrarini, Alessandra; Fisher, Richard; Flori, Elisabeth; Forer, Lukas; Gaillard, Dominique; Gerard, Marion; Gieger, Christian; Gimelli, Stefania; Gimelli, Giorgio; Grabe, Hans J; Guichet, Agnès; Guillin, Olivier; Hartikainen, Anna-Liisa; Heron, Délphine; Hippolyte, Loyse; Holder, Muriel; Homuth, Georg; Isidor, Bertrand; Jaillard, Sylvie; Jaros, Zdenek; Jiménez-Murcia, Susana; Helas, Géraldine Joly; Jonveaux, Philippe; Kaksonen, Satu; Keren, Boris; Kloss-Brandstätter, Anita; Knoers, Nine V A M; Koolen, David A; Kroisel, Peter M; Kronenberg, Florian; Labalme, Audrey; Landais, Emilie; Lapi, Elisabetta; Layet, Valérie; Legallic, Solenn; Leheup, Bruno; Leube, Barbara; Lewis, Suzanne; Lucas, Josette; MacDermot, Kay D; Magnusson, Pall; Marshall, Christian; Mathieu-Dramard, Michèle; McCarthy, Mark I; Meitinger, Thomas; Mencarelli, Maria Antonietta; Merla, Giuseppe; Moerman, Alexandre; Mooser, Vincent; Morice-Picard, Fanny; Mucciolo, Mafalda; Nauck, Matthias; Ndiaye, Ndeye Coumba; Nordgren, Ann; Pasquier, Laurent; Petit, Florence; Pfundt, Rolph; Plessis, Ghislaine; Rajcan-Separovic, Evica; Ramelli, Gian Paolo; Rauch, Anita; Ravazzolo, Roberto; Reis, Andre; Renieri, Alessandra; Richart, Cristobal; Ried, Janina S; Rieubland, Claudine; Roberts, Wendy; Roetzer, Katharina M; Rooryck, Caroline; Rossi, Massimiliano; Saemundsen, Evald; Satre, Véronique; Schurmann, Claudia; Sigurdsson, Engilbert; Stavropoulos, Dimitri J; Stefansson, Hreinn; Tengström, Carola; Thorsteinsdóttir, Unnur; Tinahones, Francisco J; Touraine, Renaud; Vallée, Louis; van Binsbergen, Ellen; Van der Aa, Nathalie; Vincent-Delorme, Catherine; Visvikis-Siest, Sophie; Vollenweider, Peter; Völzke, Henry; Vulto-van Silfhout, Anneke T; Waeber, Gérard; Wallgren-Pettersson, Carina; Witwicki, Robert M; Zwolinksi, Simon; Andrieux, Joris; Estivill, Xavier; Gusella, James F; Gustafsson, Omar; Metspalu, Andres; Scherer, Stephen W; Stefansson, Kari; Blakemore, Alexandra I F; Beckmann, Jacques S; Froguel, Philippe

    2011-10-01

    Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies

  13. An Unstable Trinucleotide-Repeat Region on Chromosome 13 Implicated in Spinocerebellar Ataxia: A Common Expansion Locus

    PubMed Central

    Vincent, John B; Neves-Pereira, Maria L.; Paterson, Andrew D.; Yamamoto, Etsuko; Parikh, Sagar V.; Macciardi, Fabio; Gurling, Hugh M.D.; Potkin, Steve G.; Pato, Carlos N.; Macedo, Antonio; Kovacs, Maria; Davies, Marilyn; Lieberman, Jeffrey A.; Meltzer, Herbert Y.; Petronis, Arturas; Kennedy, James L.

    2000-01-01

    Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual’s DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA)n (CTG)n, which is very long (∼1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (>100 repeats) were observed in 14 (1.25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d’Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology. PMID:10712198

  14. Identification and characterization of chromosomal relBE toxin-antitoxin locus in Streptomyces cattleya DSM46488

    PubMed Central

    Li, Peng; Tai, Cui; Deng, Zixin; Gan, Jianhua; Oggioni, Marco R.; Ou, Hong-Yu

    2016-01-01

    The relBE family of Type II toxin-antitoxin (TA) systems have been widely reported in bacteria but none in Streptomyces. With the conserved domain searches for TA pairs in the sequenced Streptomyces genomes, we identified two putative relBE loci, relBE1sca and relBE2sca, on the chromosome of Streptomyces cattleya DSM 46488. Overexpression of the S. cattleya toxin RelE2sca caused severe growth inhibition of E. coli and S. lividans, but RelE1sca had no toxic effect. The toxicity of RelE2sca could be abolished by the co-expression of its cognate RelB2sca antitoxin. Moreover, the RelBE2sca complex, or the antitoxin RelB2sca alone, specifically interacted with the relBE2sca operon and repressed its transcription. The relBE2sca operon transcription was induced under osmotic stress, along with the ClpP proteinase genes. The subsequent in vivo analysis showed that the antitoxin was degraded by ClpP. Interestingly, the E. coli antitoxin RelBeco was able to alleviate the toxicity of S. cattleya RelE2sca while the mutant RelB2sca(N61V&M68L) but not the wild type could alleviate the toxicity of E. coli RelEeco as well. The experimental demonstration of the relBEsca locus might be helpful to investigate the key roles of type II TA systems in Streptomyces physiology and environmental stress responses. PMID:27534445

  15. A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13

    PubMed Central

    Cho, Michael H.; Castaldi, Peter J.; Wan, Emily S.; Siedlinski, Mateusz; Hersh, Craig P.; Demeo, Dawn L.; Himes, Blanca E.; Sylvia, Jody S.; Klanderman, Barbara J.; Ziniti, John P.; Lange, Christoph; Litonjua, Augusto A.; Sparrow, David; Regan, Elizabeth A.; Make, Barry J.; Hokanson, John E.; Murray, Tanda; Hetmanski, Jacqueline B.; Pillai, Sreekumar G.; Kong, Xiangyang; Anderson, Wayne H.; Tal-Singer, Ruth; Lomas, David A.; Coxson, Harvey O.; Edwards, Lisa D.; MacNee, William; Vestbo, Jørgen; Yates, Julie C.; Agusti, Alvar; Calverley, Peter M.A.; Celli, Bartolome; Crim, Courtney; Rennard, Stephen; Wouters, Emiel; Bakke, Per; Gulsvik, Amund; Crapo, James D.; Beaty, Terri H.; Silverman, Edwin K.

    2012-01-01

    The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10−9). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV1 (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior. PMID:22080838

  16. The breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis.

    PubMed

    Baer, R; Heppell, A; Taylor, A M; Rabbitts, P H; Boullier, B; Rabbitts, T H

    1987-12-01

    T-cell tumors are characterized by inversions or translocations of chromosome 14. The breakpoints of these karyotypic abnormalities occur in chromosome bands 14q11 and 14q32--the same bands in which the T-cell receptor (TCR) alpha-chain and immunoglobulin heavy chain genes have been mapped, respectively. Patients with ataxia-telangiectasia are particularly prone to development of T-cell chronic lymphocytic leukemia with such chromosomal abnormalities. We now describe DNA rearrangements of the TCR alpha-chain gene in an ataxia-telangiectasia-associated leukemia containing both a normal and an inverted chromosome 14. The normal chromosome 14 has undergone a productive join of TCR alpha-chain variable (V alpha) and joining (J alpha) gene segments. The other allele of the TCR alpha-chain gene features a DNA rearrangement, about 50 kilobases from the TCR alpha-chain constant (C alpha) gene, that represents the breakpoint of the chromosome 14 inversion; this breakpoint is comprised of a TCR J alpha segment (from 14q11) fused to sequences derived from 14q32 but on the centromeric side of C mu. These results imply that 14q32 sequences located at an undetermined distance downstream of the immunoglobulin C mu locus can contribute to the development of T-cell tumors.

  17. Partial isodisomy for maternal chromosome 7 and short stature in an individual with a mutation at the COL1A2 locus

    SciTech Connect

    Spotila, L.D.; Sereda, L.; Prockop, D.J. )

    1992-12-01

    Uniparental disomy for chromosome 7 has been described previously in two individuals with cystic fibrosis. Here, the authors describe a third case that was discovered because the proband was homozygous for a mutation in the COL1A2 gene for type I procollagen, although his mother was heterozygous and his father did not have the mutation. Phenotypically, the proband was similar to the two previously reported cases with uniparental disomy for chromosome 7, in that he was short in stature and growth retarded. Paternity was assessed with five polymorphic markers. Chromosome 7 inheritance in the proband was analyzed using 12 polymorphic markers distributed along the entire chromosome. Similar analysis of the proband's two brothers established the phase of the alleles at the various loci, assuming minimal recombination. The proband inherited only maternal alleles at five loci and was homozygous at all loci examined, except one. He was heterozygous for an RFLP at the IGBP-1 locus at 7p13-p12. The results suggest that the isodisomy was not complete because of a recombination event involving the proximal short arms of two maternal chromosomes. In addition, the phenotype of proportional dwarfism in the proband suggests imprinting of one or more growth-related genes on chromosome 7. 42 refs., 5 figs., 3 tabs.

  18. 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

  19. Physical mapping of the major early-onset familial Alzheimer`s disease locus on chromosome 14 and analysis of candidate gene sequences

    SciTech Connect

    Tanzi, R.E.; Romano, D.M.; Crowley, A.C.

    1994-09-01

    Genetic studies of kindreds displaying evidence for familial AD (FAD) have led to the localization of gene defects responsible for this disorder on chromosomes 14, 19, and 21. A minor early-onset FAD gene on chromosome 21 has been identified to enode the amyloid precursor protein (APP), and the late-onset FAD susceptibility locus on chromosome 19 has been shown to be in linkage disequilibrium with the E4 allele of the APOE gene. Meanwhile, the locus responsible for the major form of early-onset FAD on chromosome 14q24 has not yet been identified. By recombinational analysis, we have refined the minimal candidate region containing the gene defect to approximately 3 megabases in 14q24. We will describe our laboratory`s progress on attempts to finely localize this locus, as well as test known candidate genes from this region for either inclusion in the minimal candidate region or the presence of pathogenic mutations. Candidate genes that have been tested so far include cFOS, heat shock protein 70 member (HSF2A), transforming growth factor beta (TGFB3), the trifunctional protein C1-THF synthase (MTHFD), bradykinin receptor (BR), and the E2k component of a-ketoglutarate dehydrogenase. HSP2A, E2k, MTHFD, and BR do not map to the current defined minimal candidate region; however, sequence analysis must be performed to confirm exclusion of these genes as true candidates. Meanwhile, no pathogenic mutations have yet been found in cFOS or TGFB3. We have also isolated a large number of novel transcribed sequences from the minimal candidate region in the form of {open_quotes}trapped exons{close_quotes} from cosmids identified by hybridization to select YAC clones; we are currently in the process of searching for pathogenic mutations in these exons in affected individuals from FAD families.

  20. Chromosome

    MedlinePlus

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

  1. The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids

    SciTech Connect

    Kedda, M.A.; Stevens, G.; Manga, P.; Viljoen, C.; Jenkins, T.; Ramsay, M. Univ. of Witwatersrand, Johannesburg )

    1994-06-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid [open quotes]ty-pos OCA[close quotes] individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and [open quotes]normal[close quotes] chromosomes. No haplotype showed statistically significant association with ty-pos OCA, and thus none could be used to predict the origins of the ty-pos OCA mutations. On the basis of the D15S12 results, there is evidence for multiple ty-pos OCA mutations in southern African negroids. 31 refs., 1 fig., 3 tabs.

  2. Inversa acne (hidradenitis suppurativa): a case report and identification of the locus at chromosome 1p21.1-1q25.3.

    PubMed

    Gao, Min; Wang, Pei-Guang; Cui, Yong; Yang, Sen; Zhang, Yu-Hui; Lin, Da; Zhang, Kai-Yue; Liang, Yan-Hua; Sun, Liang-Dan; Yan, Kai-Lin; Xiao, Feng-Li; Huang, Wei; Zhang, Xue-Jun

    2006-06-01

    Acne inversa (hidradenitis suppurativa) is a chronic relapsing inflammatory skin disease characterized by recurrent draining sinuses and abscesses, predominantly in skin folds that carry terminal hairs and apocrine glands. The genetic basis for this disease is unknown. In this study, we performed a genome-wide scan in a four-generation Chinese family to map the chromosome location of the responsible gene. We first identified a locus at chromosome 1p21.1-1q25.3 with the maximum logarithm of odds (LOD) score of 3.26 at the marker D1S2624 (at recombination fraction=0.00). The other two-point LOD scores >/=3 were observed at markers D1S2695, D1S2726, D1S252, and D1S2777. Haplotype analysis localized this locus to a 76 Mb region flanked by D1S248 and D1S2711. This is the first locus for the inversa acne and will be a starting point towards understanding the molecular mechanisms of this disease.

  3. Physical organization of mixed protease inhibitor gene clusters, coordinated expression and association with resistance to late blight at the StKI locus on potato chromosome III.

    PubMed

    Odeny, Damaris Achieng; Stich, Benjamin; Gebhardt, Christiane

    2010-12-01

    Protease inhibitors (PIs) play a role in plant defence against pests and pathogens as well as in plant development. Potato (Solanum tuberosum) contains abundant levels of diverse PIs. Most potato Kunitz-type inhibitor (KTI) genes map to the StKI locus on potato chromosome III, which is linked to a quantitative trait locus (QTL) for resistance to Phytophthora infestans. To elucidate the physical organization of PIs at the StKI locus, we screened bacterial artificial chromosome (BAC) libraries with KTI probes. Ten different clones were selected, sequenced and annotated. Of 100 putative genes, 22 corresponded to five PI classes. Expression analysis by quantitative real-time PCR (qRT-PCR) using PI class-specific primers in different tissues of the tetraploid potato cultivars 'Nikita' and 'Baltica' revealed different transcript levels, depending on PI type and genotype. During the compatible interaction with a complex race of P. infestans, four PI classes showed coordinated expression over 3 d after infection, a strong decrease in infected leaves and a transient induction in systemic leaves. Basal transcript levels in non-infected leaves differed strongly between the two genotypes examined. Two microsatellite markers located within the PI gene cluster were associated with resistance to P. infestans in a population of potato varieties and breeding clones. PMID:20716067

  4. Assignment of the gene encoding the 5-HT{sub 1E} serotonin receptor (S31) (locus HTR1E) to human chromosome 6q14-q15

    SciTech Connect

    Levy, F.O.; Tasken, K.; Solberg, R.

    1994-08-01

    The human gene for the 5-HT{sub 1E} serotonin receptor was recently cloned, but no chromosomal assignment has yet been given to this gene (locus HTR1E). In this work, we demonstrate by two independent polymerase chain reactions on a panel of human-hamster somatic cell hybrid genomic DNA that the 5-HT{sub 1E} serotonin receptor gene is localized on human chromosome 6. Furthermore, by means of in situ hybridization to human metaphase chromosomes, using the cloned 5-HT{sub 1E} receptor gene (phage clone {lambda}-S31) as a probe, we demonstrate that this gene is localized to the q14-q15 region on chromosome 6. Screening of genomic DNA from 15 unrelated Caucasian individuals, using as a probe the open reading frame of the cloned 5-HT{sub 1E} receptor gene, did not reveal any restriction fragment length polymorphisms with the enzymes BamHI, BanII, BglII, EcoRI, HincII, HindIII, HinfI, MspI, PstI, and PvuII. Since the 5-HT{sub 1E} receptor is found mainly in the cerebral cortex and abnormal function of the serotonergic system has been implicated in a variety of neurologic and psychiatric diseases, the precise chromosomal assignment of the 5-HT{sub 1E} receptor gene is the crucial first step toward the evaluation of this locus as a candidate for mutations in such syndromes. 28 refs., 2 figs., 2 tabs.

  5. Localization of a locus for juvenile myoclonic epilepsy on chromosome 6p11-21.2 and evidence for genetic heterogeneity

    SciTech Connect

    Liu, A.W.; Delgado-Escueta, A.V. |; Alonso, V.M.E.

    1994-09-01

    Juvenile myoclonic epilepsy (JME) is a common form of primary idiopathic generalized epilepsy characterized by myoclonias, tonic-clonic or clonic tonic-clonic convulsions and absences. Ictal electroencephalograms (EEGs) show high amplitude multispikes folowed by slow waves and interictal EEGs manifest 3.5-6 Hz diffuse multispike wave complexes. JME affected about 7-10% of patients with epilepsies and its onset peaks between 13-15 years of age. We recently mapped a JME locus on chromosome 6p21.1-6p11 by linkage analysis of one relatively large JME family from Los Angeles and Belize. Assuming autosomal dominant inheritance with 70% penetrance, pairwise analyses tightly linked JME to D6S257 (Z = 3.67), D6S428 (Z = 3.08) and D6S272 (Z = 3.56) at {theta} = 0, m = f. Recombination and multipoints linkage analysis also suggested a locus is between markers D6S257 and D6S272. We then screened three relatively larger Mexican JME pedigrees with D6S257, D6S272, D6S282, TNF, D6S276, D6S273, D6S105 and F13A1 on chromosome 6p. Assuming autosomal dominant inheritance with incomplete penetrance, linkage to chromosome 6p DNA markers are excluded. Our findings underline the genetic heterogeneity of juvenile myoclonic epilepsy.

  6. Quantitative Linkage for Autism Spectrum Disorders Symptoms in Attention-Deficit/Hyperactivity Disorder: Significant Locus on Chromosome 7q11

    ERIC Educational Resources Information Center

    Nijmeijer, Judith S.; Arias-Vásquez, Alejandro; Rommelse, Nanda N.; Altink, Marieke E.; Buschgens, Cathelijne J.; Fliers, Ellen A.; Franke, Barbara; Minderaa, Ruud B.; Sergeant, Joseph A.; Buitelaar, Jan K.; Hoekstra, Pieter J.; Hartman, Catharina A.

    2014-01-01

    We studied 261 ADHD probands and 354 of their siblings to assess quantitative trait loci associated with autism spectrum disorder symptoms (as measured by the Children's Social Behavior Questionnaire (CSBQ) using a genome-wide linkage approach, followed by locus-wide association analysis. A genome-wide significant locus for the CSBQ subscale…

  7. A novel locus for alopecia with mental retardation syndrome (APMR2) maps to chromosome 3q26.2-q26.31.

    PubMed

    Wali, A; John, P; Gul, A; Lee, K; Chishti, M S; Ali, G; Hassan, M J; Leal, S M; Ahmad, W

    2006-09-01

    Congenital alopecia may occur either alone or in association with ectodermal and other abnormalities. On the bases of such associations, several different syndromes featuring congenital alopecia can be distinguished. Alopecia with mental retardation syndrome (APMR) is a rare autosomal recessive disorder, clinically characterized by total or partial hair loss and mental retardation. In the present study, a five-generation Pakistani family with multiple affected individuals with APMR was ascertained. Patients in this family exhibited typical features of APMR syndrome. The disease locus was mapped to chromosome 3q26.2-q26.31 by carrying out a genome scan followed by fine mapping. A maximum two-point logarithm of odds (LOD) score of 2.93 at theta=0.0 was obtained at markers D3S3053 and D3S2309. Multipoint linkage analysis resulted in a maximum LOD score of 4.57 with several markers, which supports the linkage. The disease locus was flanked by markers D3S1564 and D3S2427, which corresponds to 9.6-cM region according to the Rutgers combined linkage-physical map of the human genome (build 35) and contains 5.6 Mb. The linkage interval of the APMR locus identified here does not overlap with the one described previously; therefore, this locus has been designated as APMR2.

  8. Transgenic mice containing a 248-kb yeast artificial chromosome carrying the human beta-globin locus display proper developmental control of human globin genes.

    PubMed Central

    Peterson, K R; Clegg, C H; Huxley, C; Josephson, B M; Haugen, H S; Furukawa, T; Stamatoyannopoulos, G

    1993-01-01

    Transgenic mice were generated using a purified 248-kb yeast artificial chromosome (YAC) bearing an intact 82-kb human beta-globin locus and 148 kb of flanking sequence. Seventeen of 148 F0 pups were transgenic. RNase protection analysis of RNA isolated from the blood of 13 gamma- and beta-globin-positive founders showed that only the human beta-globin gene was expressed in the adult founders. Studies of F1 and F2 fetuses demonstrated that the genes of the beta-locus YAC displayed the proper developmental switches in beta-like globin gene expression. Expression of epsilon- and gamma-globin, but not beta-globin, was observed in the yolk sac, there was only minor gamma and mostly beta expression in the 14-day liver, and only beta mRNA in the blood of the adult animals. Structural data showed that the locus was intact. These results indicate that it is now possible to dissect regulatory mechanisms within the context of an entire locus in vivo by using the ability to perform mutagenesis efficiently in yeast via homologous recombination, followed by purification of the altered YAC and its introduction into mice. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8356061

  9. Two-locus admixture linkage analysis of bipolar and unipolar affective disorder supports the presence of susceptibility loci on chromosomes 11p15 and 21q22

    SciTech Connect

    Smyth, C.; Kalsi, G.; O`Neill, J.

    1997-02-01

    Following a report of a linkage study that yielded evidence for a susceptibility locus for bipolar affective disorder on the long arm of chromosome 21, we studied 23 multiply affected pedigrees collected from Iceland and the UK, using the markers PFKL, D21S171, and D21S49. Counting only bipolar cases as affected, a two-point LOD of 1.28 was obtained using D21S171 ({theta} = 0.01, {alpha} = 0.35), with three Icelandic families producing LODs of 0.63, 0.62, and 1.74 (all at {theta} = 0.0). Affected sib pair analysis demonstrated increased allele sharing at D21S171 (P = 0.001) when unipolar cases were also considered affected. The same set of pedigrees had previously been typed for a tyrosine hydroxylase gene (TH) polymorphism at 11p15 and had shown some moderate evidence for linkage. When information from TH and the 21q markers was combined in a two-locus admixture analysis, an overall admixture LOD of 3.87 was obtained using the bipolar affection model. Thus the data are compatible with the hypothesis that a locus at or near TH influences susceptibility in some pedigrees, while a locus near D21S171 is active in others. Similar analyses in other datasets should be carried out to confirm or refute our tentative finding. 66 refs., 3 tabs.

  10. Gene by Environment Interaction Linking the Chromosome 15q25 Locus With Cigarette Consumption and Lung Cancer Susceptibility--Are African American Affected Differently?

    PubMed

    Hopkins, R J; Young, R P

    2016-02-01

    The majority of lung cancer cases result from complex interactions between smoking exposure, genetic susceptibility and a person's immune response to chronic inflammation or lung remodelling. Epidemiological studies confirm that susceptibility to developing chronic obstructive pulmonary disease (COPD), especially emphysema, is also closely linked to lung cancer susceptibility. Genetic epidemiology studies have consistently reported associations between the chromosome 15q25 locus with lung cancer and COPD. In addition, studies show this locus to be independently associated with cigarette consumption and nicotine addiction in a dose-response manner, primarily at lower levels of cigarette consumption. Studies that measure both cigarette consumption and lung function, together with extensive genotype analysis, will be needed to further unravel these complex relationships.

  11. Gene by Environment Interaction Linking the Chromosome 15q25 Locus With Cigarette Consumption and Lung Cancer Susceptibility — Are African American Affected Differently?

    PubMed Central

    Hopkins, R.J.; Young, R.P.

    2016-01-01

    The majority of lung cancer cases result from complex interactions between smoking exposure, genetic susceptibility and a person's immune response to chronic inflammation or lung remodelling. Epidemiological studies confirm that susceptibility to developing chronic obstructive pulmonary disease (COPD), especially emphysema, is also closely linked to lung cancer susceptibility. Genetic epidemiology studies have consistently reported associations between the chromosome 15q25 locus with lung cancer and COPD. In addition, studies show this locus to be independently associated with cigarette consumption and nicotine addiction in a dose-response manner, primarily at lower levels of cigarette consumption. Studies that measure both cigarette consumption and lung function, together with extensive genotype analysis, will be needed to further unravel these complex relationships. PMID:27014742

  12. Gene by Environment Interaction Linking the Chromosome 15q25 Locus With Cigarette Consumption and Lung Cancer Susceptibility--Are African American Affected Differently?

    PubMed

    Hopkins, R J; Young, R P

    2016-02-01

    The majority of lung cancer cases result from complex interactions between smoking exposure, genetic susceptibility and a person's immune response to chronic inflammation or lung remodelling. Epidemiological studies confirm that susceptibility to developing chronic obstructive pulmonary disease (COPD), especially emphysema, is also closely linked to lung cancer susceptibility. Genetic epidemiology studies have consistently reported associations between the chromosome 15q25 locus with lung cancer and COPD. In addition, studies show this locus to be independently associated with cigarette consumption and nicotine addiction in a dose-response manner, primarily at lower levels of cigarette consumption. Studies that measure both cigarette consumption and lung function, together with extensive genotype analysis, will be needed to further unravel these complex relationships. PMID:27014742

  13. Fine Mapping of a Dravet Syndrome Modifier Locus on Mouse Chromosome 5 and Candidate Gene Analysis by RNA-Seq

    PubMed Central

    Hawkins, Nicole A.; Zachwieja, Nicole J.; Miller, Alison R.; Anderson, Lyndsey L.; Kearney, Jennifer A.

    2016-01-01

    A substantial number of mutations have been identified in voltage-gated sodium channel genes that result in various forms of human epilepsy. SCN1A mutations result in a spectrum of severity ranging from mild febrile seizures to Dravet syndrome, an infant-onset epileptic encephalopathy. Dravet syndrome patients experience multiple seizures types that are often refractory to treatment, developmental delays, and elevated risk for SUDEP. The same sodium channel mutation can produce epilepsy phenotypes of varying clinical severity. This suggests that other factors, including genetic, modify the primary mutation and change disease severity. Mouse models provide a useful tool in studying the genetic basis of epilepsy. The mouse strain background can alter phenotype severity, supporting a contribution of genetic modifiers in epilepsy. The Scn1a+/- mouse model has a strain-dependent epilepsy phenotype. Scn1a+/- mice on the 129S6/SvEvTac (129) strain have a normal phenotype and lifespan, while [129xC57BL/6J]F1-Scn1a+/- mice experience spontaneous seizures, hyperthermia-induced seizures and high rates of premature death. We hypothesize the phenotypic differences are due to strain-specific genetic modifiers that influence expressivity of the Scn1a+/- phenotype. Low resolution mapping of Scn1a+/- identified several Dravet syndrome modifier (Dsm) loci responsible for the strain-dependent difference in survival. One locus of interest, Dsm1 located on chromosome 5, was fine mapped to a 9 Mb region using interval specific congenics. RNA-Seq was then utilized to identify candidate modifier genes within this narrowed region. Three genes with significant total gene expression differences between 129S6/SvEvTac and [129xC57BL/6J]F1 were identified, including the GABAA receptor subunit, Gabra2. Further analysis of Gabra2 demonstrated allele-specific expression. Pharmological manipulation by clobazam, a common anticonvulsant with preferential affinity for the GABRA2 receptor, revealed

  14. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus

    PubMed Central

    Jacquemont, Sébastien; Reymond, Alexandre; Zufferey, Flore; Harewood, Louise; Walters, Robin G.; Kutalik, Zoltán; Martinet, Danielle; Shen, Yiping; Valsesia, Armand; Beckmann, Noam D.; Thorleifsson, Gudmar; Belfiore, Marco; Bouquillon, Sonia; Campion, Dominique; De Leeuw, Nicole; De Vries, Bert B. A.; Esko, Tõnu; Fernandez, Bridget A.; Fernández-Aranda, Fernando; Fernández-Real, José Manuel; Gratacòs, Mònica; Guilmatre, Audrey; Hoyer, Juliane; Jarvelin, Marjo-Riitta; Kooy, Frank R.; Kurg, Ants; Le Caignec, Cédric; Männik, Katrin; Platt, Orah S.; Sanlaville, Damien; Van Haelst, Mieke M.; Villatoro Gomez, Sergi; Walha, Faida; Wu, Bai-Lin; Yu, Yongguo; Aboura, Azzedine; Addor, Marie-Claude; Alembik, Yves; Antonarakis, Stylianos E.; Arveiler, Benoît; Barth, Magalie; Bednarek, Nathalie; Béna, Frédérique; Bergmann, Sven; Beri, Mylène; Bernardini, Laura; Blaumeiser, Bettina; Bonneau, Dominique; Bottani, Armand; Boute, Odile; Brunner, Han G.; Cailley, Dorothée; Callier, Patrick; Chiesa, Jean; Chrast, Jacqueline; Coin, Lachlan; Coutton, Charles; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; David, Albert; De Freminville, Bénédicte; Delobel, Bruno; Delrue, Marie-Ange; Demeer, Bénédicte; Descamps, Dominique; Didelot, Gérard; Dieterich, Klaus; Disciglio, Vittoria; Doco-Fenzy, Martine; Drunat, Séverine; Duban-Bedu, Bénédicte; Dubourg, Christèle; El-Sayed Moustafa, Julia S.; Elliott, Paul; Faas, Brigitte H. W.; Faivre, Laurence; Faudet, Anne; Fellmann, Florence; Ferrarini, Alessandra; Fisher, Richard; Flori, Elisabeth; Forer, Lukas; Gaillard, Dominique; Gerard, Marion; Gieger, Christian; Gimelli, Stefania; Gimelli, Giorgio; Grabe, Hans J.; Guichet, Agnès; Guillin, Olivier; Hartikainen, Anna-Liisa; Heron, Délphine; Hippolyte, Loyse; Holder, Muriel; Homuth, Georg; Isidor, Bertrand; Jaillard, Sylvie; Jaros, Zdenek; Jiménez-Murcia, Susana; Joly Helas, Géraldine; Jonveaux, Philippe; Kaksonen, Satu; Keren, Boris; Kloss-Brandstätter, Anita; Knoers, Nine V. A. M.; Koolen, David A.; Kroisel, Peter M.; Kronenberg, Florian; Labalme, Audrey; Landais, Emilie; Lapi, Elisabetta; Layet, Valérie; Legallic, Solenn; Leheup, Bruno; Leube, Barbara; Lewis, Suzanne; Lucas, Josette; Macdermot, Kay D.; Magnusson, Pall; Marshall, Christian R.; Mathieu-Dramard, Michèle; Mccarthy, Mark I.; Meitinger, Thomas; Antonietta Mencarelli, Maria; Merla, Giuseppe; Moerman, Alexandre; Mooser, Vincent; Morice-Picard, Fanny; Mucciolo, Mafalda; Nauck, Matthias; Coumba Ndiaye, Ndeye; Nordgren, Ann; Pasquier, Laurent; Petit, Florence; Pfundt, Rolph; Plessis, Ghislaine; Rajcan-Separovic, Evica; Paolo Ramelli, Gian; Rauch, Anita; Ravazzolo, Roberto; Reis, Andre; Renieri, Alessandra; Richart, Cristobal; Ried, Janina S.; Rieubland, Claudine; Roberts, Wendy; Roetzer, Katharina M.; Rooryck, Caroline; Rossi, Massimiliano; Saemundsen, Evald; Satre, Véronique; Schurmann, Claudia; Sigurdsson, Engilbert; Stavropoulos, Dimitri J.; Stefansson, Hreinn; Tengström, Carola; Thorsteinsdóttir, Unnur; Tinahones, Francisco J.; Touraine, Renaud; Vallée, Louis; Van Binsbergen, Ellen; Van Der Aa, Nathalie; Vincent-Delorme, Catherine; Visvikis-Siest, Sophie; Vollenweider, Peter; Völzke, Henry; Vulto-Van Silfhout, Anneke T.; Waeber, Gérard; Wallgren-Pettersson, Carina; Witwicki, Robert M.; Zwolinksi, Simon; Andrieux, Joris; Estivill, Xavier; Gusella, James F.; Gustafsson, Omar; Metspalu, Andres; Scherer, Stephen W.; Stefansson, Kari; Blakemore, Alexandra I. F.; Beckmann, Jacques S.; Froguel, Philippe

    2011-01-01

    Both underweight and obesity have been associated with increased mortality1,2. Underweight, defined as body mass index (BMI) ≤ 18,5 kg/m2 in adults 3 and ≤ −2 standard deviations (SD) in children4,5, is the main sign of a series of heterogeneous clinical conditions such as failure to thrive (FTT) 6–8, feeding and eating disorder and/or anorexia nervosa9,10. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported 11, 12. We previously demonstrated that hemizygosity of a ~600 kb region on the short arm of chromosome 16 (chr16:29.5–30.1Mb), causes a highly-penetrant form of obesity often associated with hyperphagia and intellectual disabilities13. Here we show that the corresponding reciprocal duplication is associated with underweight. We identified 138 (132 novel cases) duplication carriers (108 unrelated carriers) from over 95,000 individuals clinically-referred for developmental or intellectual disabilities (DD/ID), psychiatric disorders or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight (mean Z-score −0.6; p=4.4×10−4) and BMI (mean Z-score −0.5; p=2.0×10−3). In particular, half of the boys younger than 5 years are underweight with a probable diagnosis of FTT, while adult duplication carriers have an 8.7-fold (p=5.9×10−11; CI_95=[4.5–16.6]) increased risk of being clinically underweight. We observe a significant trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive feeding behaviours and a significant reduction in head circumference (mean Z-score −0.9; p=7.8×10−6). Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus, correlating with changes in transcript levels for genes mapping within the duplication but not within flanking

  15. A multiple resistance locus on chromosome arm 3BS in wheat confers resistance to stem rust (Sr2), leaf rust (Lr27) and powdery mildew.

    PubMed

    Mago, R; Tabe, L; McIntosh, R A; Pretorius, Z; Kota, R; Paux, E; Wicker, T; Breen, J; Lagudah, E S; Ellis, J G; Spielmeyer, W

    2011-08-01

    Sr2 is the only known durable, race non-specific adult plant stem rust resistance gene in wheat. The Sr2 gene was shown to be tightly linked to the leaf rust resistance gene Lr27 and to powdery mildew resistance. An analysis of recombinants and mutants suggests that a single gene on chromosome arm 3BS may be responsible for resistance to these three fungal pathogens. The resistance functions of the Sr2 locus are compared and contrasted with those of the adult plant resistance gene Lr34.

  16. Exclusion of one pedigree affected by adult onset primary open angle glaucoma from linkage to the juvenile glaucoma locus on chromosome 1q21-q31.

    PubMed Central

    Avramopoulos, D; Kitsos, G; Economou-Petersen, E; Grigoriadou, M; Vassilopoulos, D; Papageorgiou, C; Psilas, K; Petersen, M B

    1996-01-01

    A locus for autosomal dominant juvenile onset primary open angle glaucoma (POAG) was recently assigned to chromosome region 1q21-q31. In the present study, a large Greek family with autosomal dominant adult onset POAG was investigated using microsatellite markers. Exclusion of linkage of the adult onset POAG gene to the region D1S194-D1S191 was obtained in this pedigree. Therefore, the data provide evidence that juvenile and adult onset POAG are genetically distinct disease entities. PMID:9004141

  17. Fine genetic mapping of the Batten disease locus (CLN3) by haplotype analysis and demonstration of allelic association with chromosome 16p microsatellite loci

    SciTech Connect

    Mitchison, H.M.; McKay, T.R.; Thompson, A.D.; Mulley, J.C.; Kozman, H.M.; Richards, R.I.; Callen, D.F.; Stallings, R.L.; Doggett, N.A.; Attwood, J.

    1993-05-01

    Batten disease, juvenile onset neuronal ceroid lipofuscinosis, is an autosomal recessive neurodegenerative disorder characterized by accumulation of autofluorescent lipopigment in neurons and other cell types. The disease locus (CLN3) has previously been assigned to chromosome 16p. The genetic localization of CLN3 has been refined by analyzing 70 families using a high-resolution map of 15 marker loci encompassing the CLN3 region on 16p. Crossovers in three maternal meioses allowed localization of CLN3 to the interval between D16S297 and D16S57. Within that interval alleles at three highly polymorphic dinucleotide repeat loci (D16S288, D16S298, D16S299) were found to be in strong linkage disequilibrium with CLN3. Analysis of haplotypes suggests that a majority of CLN3 chromosomes have arisen from a single founder mutation. 15 refs., 2 figs., 5 tabs.

  18. Linkage analyses of chromosome 18 markers do not identify a major susceptibility locus for bipolar affective disorder in the Old Order Amish

    SciTech Connect

    Pauls, D.L.; Paul, S.M. |; Allen, C.R.

    1995-09-01

    Previously reported linkage of bipolar affective disorder to DNA markers in the pericentromeric region of chromosome 18 was reexamined in a larger homogeneous sample of Old Order Amish families. Four markers (D18S21, D18S53, D18S44, and D18S40) were examined in three kindreds containing 31 bipolar I (BP I) individuals. Although linkage findings were replicated in the one previously studied Amish pedigree containing four BP I individuals, linkage to this region was excluded in the larger sample. If a susceptibility locus for bipolar disorder is located in this region of chromosome 18, it is of minor significance in this population. 40 refs., 1 fig., 5 tabs.

  19. Mating-type switching by chromosomal inversion in methylotrophic yeasts suggests an origin for the three-locus Saccharomyces cerevisiae system.

    PubMed

    Hanson, Sara J; Byrne, Kevin P; Wolfe, Kenneth H

    2014-11-11

    Saccharomyces cerevisiae has a complex system for switching the mating type of haploid cells, requiring the genome to have three mating-type (MAT)-like loci and a mechanism for silencing two of them. How this system originated is unknown, because the three-locus system is present throughout the family Saccharomycetaceae, whereas species in the sister Candida clade have only one locus and do not switch. Here we show that yeasts in a third clade, the methylotrophs, have a simpler two-locus switching system based on reversible inversion of a section of chromosome with MATa genes at one end and MATalpha genes at the other end. In Hansenula polymorpha the 19-kb invertible region lies beside a centromere so that, depending on the orientation, either MATa or MATalpha is silenced by centromeric chromatin. In Pichia pastoris, the orientation of a 138-kb invertible region puts either MATa or MATalpha beside a telomere and represses transcription of MATa2 or MATalpha2. Both species are homothallic, and inversion of their MAT regions can be induced by crossing two strains of the same mating type. The three-locus system of S. cerevisiae, which uses a nonconservative mechanism to replace DNA at MAT, likely evolved from a conservative two-locus system that swapped genes between expression and nonexpression sites by inversion. The increasing complexity of the switching apparatus, with three loci, donor bias, and cell lineage tracking, can be explained by continuous selection to increase sporulation ability in young colonies. Our results provide an evolutionary context for the diversity of switching and silencing mechanisms.

  20. A new locus on chromosome 22q13.31 linked to recessive genetic epilepsy with febrile seizures plus (GEFS+) in a Tunisian consanguineous family

    PubMed Central

    2013-01-01

    Background Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with extremely variable expressivity. The aim of our study was to identify the responsible locus for GEFS+ syndrome in a consanguineous Tunisian family showing three affected members, by carrying out a genome-wide single nucleotide polymorphisms (SNPs) genotyping followed by a whole-exome sequencing. We hypothesized an autosomal recessive (AR) mode of inheritance. Results Parametric linkage analysis and haplotype reconstruction identified a new unique identical by descent (IBD) interval of 527 kb, flanking by two microsatellite markers, 18GTchr22 and 15ACchr22b, on human chromosome 22q13.31 with a maximum multipoint LOD score of 2.51. Our analysis was refined by the use of a set of microsatellite markers. We showed that one of them was homozygous for the same allele in all affected individuals and heterozygous in healthy members of this family. This microsatellite marker, we called 17ACchr22, is located in an intronic region of TBC1D22A gene, which encodes a GTPase activator activity. Whole-exome sequencing did not reveal any mutation on chromosome 22q13.31 at the genome wide level. Conclusions Our findings suggest that TBC1D22A is a new locus for GEFS+. PMID:24067191

  1. Isolated familial somatotropinomas: establishment of linkage to chromosome 11q13.1-11q13.3 and evidence for a potential second locus at chromosome 2p16-12.

    PubMed

    Gadelha, M R; Une, K N; Rohde, K; Vaisman, M; Kineman, R D; Frohman, L A

    2000-02-01

    The majority of somatotropinomas are sporadic, although a small number occur with a familial aggregation, either as a component of an endocrine neoplasia complex that includes multiple endocrine neoplasia type 1 (MEN-1) and Carney complex (CNC) or as isolated familial somatotropinomas (IFS). IFS is defined as the occurrence of at least two cases of acromegaly or gigantism in a family that does not exhibit MEN-1 or CNC. This rare disease is associated with loss of heterozygosity (LOH) on chromosome 11q13, the locus of the MEN-1 gene, although the MEN-1 sequence and expression appear normal. These data suggest the presence of another tumor suppressor gene located at 11q13 that is important in the control of somatotrope proliferation. To establish linkage of IFS to 11q13 and to define the candidate interval of the IFS gene, we performed haplotype and allelotype analyses on two families with IFS. Collectively, allelic retention in one tumor and a recombinant haplotype in an affected individual mapped the tumor suppressor gene involved in the pathogenesis of IFS to a region of 8.6 cM between polymorphic microsatellite markers D11S1335 and INT-2 located at chromosome 11q13.1-13.3. Maximum two-point LOD scores for five markers within this region were 3.0 or more at theta = 0.0. As somatotropinomas are the predominant pituitary tumor subtype associated with CNC and arise before 30 yr of age, which is strikingly similar to the age at diagnosis for IFS, we explored the possibility that the putative CNC genes might also contribute to the pathogenesis of IFS. Although the genetic defect responsible for the complex is unknown, CNC has been mapped by linkage analysis to chromosomes 2p15-16 and 17q23-24 in different kindreds. Two-point LOD scores less than -2.0 were obtained using marker D17S949 from chromosome 17q23-24, excluding linkage. However, LOD scores of 2.5 were obtained for markers within 2p16-12; therefore, linkage of IFS to chromosome 2p cannot be excluded. This

  2. Close linkage of the locus for X chromosome-linked severe combined immunodeficiency to polymorphic DNA markers in Xq11-q13

    SciTech Connect

    de Saint Basile, G.; Arveiler, B.; Oberle, I.; Malcolm, S.; Levinsky, R.J.; Lau, Y.L.; Hofker, M.; Debre, M.; Fischer, A.; Griscelli, C.; Mandel, J.L.

    1987-11-01

    The gene for X chromosome-linked severe combined immunodeficiency (SCID), a disease characterized by a block in early T-cell differentiation, has been mapped to the region Xq11-q13 by linkage analysis with restriction fragment length polymorphisms. High logarithm of odds (lod) scores were obtained with the marker 19.2 (DXS3) and with the marker cpX73 (DXS159) that showed complete cosegregation with the disease locus in the informative families analyzed. Other significant linkages were obtained with several markers from Xq11 to q22. With the help of a recently developed genetic map of the region, it was possible to perform multipoint linkage analysis, and the most likely genetic order is DXS1-(SCID, DXS159)-DXYS1-DXYS12-DXS3, with a maximum multipoint logarithm of odds score of 11.0. The results demonstrate that the SCID locus (gene symbol IMD4) is not closely linked to the locus of Bruton's agammaglobulinemia (a defect in B-cell maturation). They also provide a way for a better estimation of risk for carrier and antenatal diagnosis.

  3. A pharmacogenetic approach to blood pressure in Lyon hypertensive rats. A chromosome 2 locus influences the response to a calcium antagonist.

    PubMed Central

    Vincent, M; Samani, N J; Gauguier, D; Thompson, J R; Lathrop, G M; Sassard, J

    1997-01-01

    In a backcross population (n = 281) derived from a cross of the Lyon hypertensive rat with Lyon normotensive rat, we investigated whether genetic factors influence the acute cardiovascular responses to pharmacological modulation of the renin-angiotensin system, the sympathetic nervous system, and the voltage-sensitive L-type calcium channels. Using microsatellite markers, a quantitative trait locus was identified and mapped on rat chromosome 2 that specifically influences the systolic (peak LOD score 4.4) and diastolic (peak LOD score 4.1) blood pressure responses to administration of a dihydropyridine calcium antagonist, PY108-068. The locus accounted for 10.3 and 10.4% of the total variances in the systolic and diastolic responses to PY108-068, respectively. In marked contrast, the locus had no effect on either basal blood pressure or on the responses to acute administration of a ganglionic blocking agent, trimetaphan, or of an angiotensin II subtype 1 receptor antagonist, losartan. These findings provide strong direct support for the paradigm that genetic factors may influence the response to antihypertensive drugs and suggest that the heterogeneity seen in the responses to different antihypertensive agents in human essential hypertension may have a significant genetic determination. PMID:9329963

  4. Fine mapping of the autosomal dominant split hand/split foot locus on chromosome 7, band q21. 3-q. 22. 1

    SciTech Connect

    Scherer, S.W.; Tsui, L.C. ); Allen, T.; Kim, J.; Soder, S. ); Poorkaj, P.; Geshuri, D.; Nunes, M.; Stephens, K.; Pagon, R.A. )

    1994-07-01

    Split hand/split foot (SHFD) is a human developmental defect characterized by missing digits, fusion of remaining digits, and a deep median cleft in the hands and feet. Cytogenetic studies of deletions and translocations associated with this disorder have indicated that an autosomal dominant split hand/split foot locus (gene SHFD1) maps to 7q21-q22. To characterize the SHFD1 locus, somatic cell hybrid lines were constructed from cytogenetically abnormal individuals with SHFD. Molecular analysis resulted in the localization of 93 DNA markers to one of 10 intervals surrounding the SHFD1 locus. The translocation breakpoints in four SHFD patients were encompassed by the smallest region of overlap among the SHFD-associated deletions. The order of DNA markers in the SHFD1 critical region has been defined as PON-D7S812-SHFD1-D7S811-ASNS. One DNA marker, D7S811, detected altered restriction enzyme fragments in three patients with translocations when examined by pulsed-field gel electrophoresis (PFGE). These data map SHFD1, a gene that is crucial for human limb differentiation, to a small interval in the q21.3-q.22.1 region of human chromosome 7. 54 refs., 4 figs., 2 tabs.

  5. 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.

  6. Mapping of Mcs30, a New Mammary Carcinoma Susceptibility Quantitative Trait Locus (QTL30) on Rat Chromosome 12: Identification of Fry as a Candidate Mcs Gene

    PubMed Central

    Ren, Xuefeng; Graham, Jessica C.; Jing, Lichen; Mikheev, Andrei M.; Gao, Yuan; Lew, Jenny Pan; Xie, Hong; Kim, Andrea S.; Shang, Xiuling; Friedman, Cynthia; Vail, Graham; Fang, Ming Zhu; Bromberg, Yana; Zarbl, Helmut

    2013-01-01

    Rat strains differ dramatically in their susceptibility to mammary carcinogenesis. On the assumption that susceptibility genes are conserved across mammalian species and hence inform human carcinogenesis, numerous investigators have used genetic linkage studies in rats to identify genes responsible for differential susceptibility to carcinogenesis. Using a genetic backcross between the resistant Copenhagen (Cop) and susceptible Fischer 344 (F344) strains, we mapped a novel mammary carcinoma susceptibility (Mcs30) locus to the centromeric region on chromosome 12 (LOD score of ∼8.6 at the D12Rat59 marker). The Mcs30 locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes comprising this locus, we identified Fry, the rat ortholog of the furry gene of Drosophila melanogaster, as a candidate Mcs gene. We cloned and determined the complete nucleotide sequence of the 13 kbp Fry mRNA. Sequence analysis indicated that the Fry gene was highly conserved across evolution, with 90% similarity of the predicted amino acid sequence among eutherian mammals. Comparison of the Fry sequence in the Cop and F344 strains identified two non-synonymous single nucleotide polymorphisms (SNPs), one of which creates a putative, de novo phosphorylation site. Further analysis showed that the expression of the Fry gene is reduced in a majority of rat mammary tumors. Our results also suggested that FRY activity was reduced in human breast carcinoma cell lines as a result of reduced levels or mutation. This study is the first to identify the Fry gene as a candidate Mcs gene. Our data suggest that the SNPs within the Fry gene contribute to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis. These results provide the foundation for analyzing the role of the human FRY gene in cancer susceptibility and progression. PMID:24023717

  7. Evidence of Chromosomal Breaks near the Mating-Type Locus of SACCHAROMYCES CEREVISIAE That Accompany MATalpha xMATalpha Matings.

    PubMed

    McCusker, J H; Haber, J E

    1981-11-01

    In order for two heterothallic MATalpha haploids of Saccharomyces cerevisiae to mate, one parent must apparently become, at least transiently, an a-like cell. Only about 25% of the matings result from an actual transposition of MATa sequences to replace MATalpha, and about 1% result from a deletion joining MAT to the normally silent HMRa allele. The majority of matings occur after an apparent chromosome break that deletes MATalpha and all of the known markers more distal on the right arm of chromosome III.--The chromosome break occurs at or very near MAT, invariably leaving the distal marker tsm1 hemizygous, but the closely linked proximal marker cry1 usually is heterozygous. The resulting diploid containing the broken chromosome is mitotically unstable; about 10% of the colonies contain visible sectors in which the rest of the broken chromosome is lost. The region close to the breakpoint (i.e., cry1) is unusually active in recombination. About 20% of the intact homologues remaining after chromosome loss were gene-converted for cry1. In addition, the broken end participated in reciprocal recombination events that joined the chromosome to the distal portion of the intact homologous chromosome.--The unstable diploids may also become stable and no longer give rise to mitotic segregants. We have found two distinct ways in which stabilization occurs. Most often the diploid becomes euploid by a recombination event that yields a cell homozygous for all markers distal to (and sometimes including) cry1. In one of 9 cases so far analyzed, the stable diploid was still hemizygous for MATalpha and for other markers distal to MAT. This last case is similar to the healing of broken chromosomes in maize described by McClintock (1939, 1941, 1951).

  8. Physical mapping of the split hand/split foot (SHSF) locus on chromosome 7 reveals a relationship between SHSF and the syndromic ectrodactylies

    SciTech Connect

    Poorkaj, P.; Nunes, M.E.; Geshuri, D.

    1994-09-01

    Split hand/split foot (also knows as ectrodactyly) is a human developmental malformation characterized by missing digits and claw-like extremities. An autosomal dominant form of this disorder has been mapped to 7q21.3-q22.1 on the basis of SHSF-associated chromosomal rearrangements: this locus has been designated SHFD1. We have constructed a physical map of the SHFD1 region that consists of contiguous yeast artificial chromosome clones and spans approximately 8 Mb. Somatic cell hybrid and fluorescent in situ hybridization analyses were used to define SHSF-associated chromosomal breakpoints in fourteen patients. A critical interval of about 1 Mb was established for SHFD1 by analysis of six patients with deletions. Translocation and inversion breakpoints in seven other patients were found to localize within a 500-700 kb interval within the critical region. Several candidate genes including DLX5 and DLX6 (members of the Drosophilia Distal-less homeobox-containing gene family) localize to this region. At least four of these genes are expressed in the developing mouse limb bud. Of particular interest is the observation that 8 of the 14 patients studied have syndromic ectrodactyly, which is characterized by the association of SHSF with a variety of other anomalies including cleft lip/palate, ectodermal dysplasia, and renal anomalies. Thus, these data implicate a single gene or cluster of genes at the SHFD1 locus in a wide range of developmental processes and serve to establish a molecular genetic relationship between simple SHSF and a broad group of human birth defects.

  9. 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.

  10. Identification of YAC clones for human chromosome 1p32 and physical mapping of the infantile neuronal ceroid lipofuscinosis (INCL) locus

    SciTech Connect

    Hellsten, E.; Vesa, J.; Peltonen, L.

    1995-01-20

    Infantile neuronal ceroid lipofuscinosis (INCL, CLN1) is a neurodegenerative disorder in which the biochemical defect is unknown. We earlier assigned the disease locus to chromosome 1p32 in the immediate vicinity of the highly informative HY-TM1 marker by linkage and linkage disequilibrium analysis. Here we report the construction of PFGE maps on the CLN1 region covering a total of 4 Mb of this relatively poorly mapped chromosomal region. We established the order of loci at 1p32 as tel-D1S57-L-myc-HY-TM1-rlf-COL9A2-D1S193-D1S62-D1S211-cen by combining data obtained from analysis of a chromosome 1 somatic cell hybrid panel, PFGE, and interphase FISH. We isolated YACs and constructed two separate YAC contigs, the loci L-myc, HY-TM1, rlf, and COL9A2 being present on a 1000-kb contig and the markers D1S193, D1S62, and D1S211 on a YAC contig spanning a maximum of 860 kb. Within the 1000-kb contig we were able to identify five CpG islands in addition to those associated with the earlier cloned genes. The YAC contigs as well as the physical map provide us with tools for the identification of the INCL gene. 36 refs., 4 figs., 3 tabs.

  11. Genome-wide SNP scan in a porcine Large White×Minzhu intercross population reveals a locus influencing muscle mass on chromosome 2.

    PubMed

    Liu, Xin; Wang, Li Gang; Luo, Wei Zhen; Li, Yong; Liang, Jing; Yan, Hua; Zhao, Ke Bin; Wang, Li Xian; Zhang, Long Chao

    2014-12-01

    A high-density single nucleotide polymorphism (SNP) array containing 62 163 markers was employed for a genome-wide association study (GWAS) to identify variants associated with lean meat in ham (LMH, %) and lean meat percentage (LMP, %) within a porcine Large White×Minzhu intercross population. For each individual, LMH and LMP were measured after slaughter at the age of 240±7 days. A total of 557 F2 animals were genotyped. The GWAS revealed that 21 SNPs showed significant genome-wide or chromosome-wide associations with LMH and LMP by the Genome-wide Rapid Association using Mixed Model and Regression-Genomic Control approach. Nineteen significant genome-wide SNPs were mapped to the distal end of Sus Scrofa Chromosome (SSC) 2, where a major known gene responsible for muscle mass, IGF2 is located. A conditioned analysis, in which the genotype of the strongest associated SNP is included as a fixed effect in the model, showed that those significant SNPs on SSC2 were derived from a single quantitative trait locus. The two chromosome-wide association SNPs on SSC1 disappeared after conditioned analysis suggested the association signal is a false association derived from using a F2 population. The present result is expected to lead to novel insights into muscle mass in different pig breeds and lays a preliminary foundation for follow-up studies for identification of causal mutations for subsequent application in marker-assisted selection programs for improving muscle mass in pigs.

  12. Structural alterations of the c-mos locus in benign pleomorphic adenomas with chromosome abnormalities of 8q12.

    PubMed

    Stenman, G; Sahlin, P; Mark, J; Landys, D

    1991-07-01

    Recent mapping studies have assigned the human c-mos proto-oncogene to chromosome 8, bands q11-12. This region is frequently affected by chromosomal translocations in benign pleomorphic adenomas of the salivary glands. Using Southern blot analysis we report here that the c-mos gene and its flanking sequences are structurally altered in pleomorphic adenomas with chromosomal rearrangements of 8q12. Rearrangements were detected in two out of 23 tumors. Restriction fragment analysis indicated that the rearrangements were due to multiple, subtle mutations involving the c-mos open reading frame and its flanking sequences. There was no direct evidence of translocation of mos in any of the tumors. Control DNAs from the two patients showed a normal restriction pattern for all enzymes tested, indicating that the rearrangements are tumor specific. Collectively, our cytogenetic and molecular data suggest involvement of the c-mos gene in the pathogenesis of pleomorphic adenomas.

  13. Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ.

    PubMed

    Eicher, John D; Powers, Natalie R; Miller, Laura L; Mueller, Kathryn L; Mascheretti, Sara; Marino, Cecilia; Willcutt, Erik G; DeFries, John C; Olson, Richard K; Smith, Shelley D; Pennington, Bruce F; Tomblin, J Bruce; Ring, Susan M; Gruen, Jeffrey R

    2014-07-01

    Reading disability (RD) and language impairment (LI) are common neurodevelopmental disorders with moderately strong genetic components and lifelong implications. RD and LI are marked by unexpected difficulty acquiring and processing written and verbal language, respectively, despite adequate opportunity and instruction. RD and LI-and their associated deficits-are complex, multifactorial, and often comorbid. Genetic studies have repeatedly implicated the DYX2 locus, specifically the genes DCDC2 and KIAA0319, in RD, with recent studies suggesting they also influence LI, verbal language, and cognition. Here, we characterize the relationship of the DYX2 locus with RD, LI, and IQ. To accomplish this, we developed a marker panel densely covering the 1.4 Mb DYX2 locus and assessed association with reading, language, and IQ measures in subjects from the Avon Longitudinal Study of Parents and Children. We then replicated associations in three independent, disorder-selected cohorts. As expected, there were associations with known RD risk genes KIAA0319 and DCDC2. In addition, we implicated markers in or near other DYX2 genes, including TDP2, ACOT13, C6orf62, FAM65B, and CMAHP. However, the LD structure of the locus suggests that associations within TDP2, ACOT13, and C6orf62 are capturing a previously reported risk variant in KIAA0319. Our results further substantiate the candidacy of KIAA0319 and DCDC2 as major effector genes in DYX2, while proposing FAM65B and CMAHP as new DYX2 candidate genes. Association of DYX2 with multiple neurobehavioral traits suggests risk variants have functional consequences affecting multiple neurological processes. Future studies should dissect these functional, possibly interactive relationships of DYX2 candidate genes. PMID:24509779

  14. 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

  15. The Yersinia kristensenii O11 O-antigen gene cluster was acquired by lateral gene transfer and incorporated at a novel chromosomal locus.

    PubMed

    Cunneen, Monica M; Reeves, Peter R

    2007-06-01

    We have sequenced the O-antigen gene clusters for the Escherichia coli O98 and Yersinia kristensenii O11 O antigens. The basic structures of these O antigens are identical, and the sequence data indicate that Y. kristensenii O11 gained its O-antigen gene cluster by lateral gene transfer (LGT). Escherichia coli O98 has a typical O-antigen gene cluster between galF and gnd as is usual in E. coli. However, the O-antigen gene cluster of Y. kristensenii O11 is not located at the traditional Yersinia O-antigen gene cluster locus, between hemH and gsk, but at a novel chromosomal locus between aroA and cmk where it is flanked by remnant galF and gnd genes that indicate the probable source of the gene cluster. Phylogenetic analysis indicated that the source was not E. coli itself but a species in the Escherichia, Salmonella, and Klebsiella group of genera. Although other O-antigen studies imply LGT on the basis of the hypervariability of the loci and GC content, this report also identifies a potential donor and provides evidence for the mechanism involved. Remnant insertion sequence (IS) sequences flank the galF and gnd remnants and suggest that LGT of the gene cluster was IS mediated.

  16. Filling in the Gap of Human Chromosome 4: Single Molecule Real Time Sequencing of Macrosatellite Repeats in the Facioscapulohumeral Muscular Dystrophy Locus

    PubMed Central

    Morioka, Masaki Suimye; Kitazume, Miwako; Osaki, Ken; Wood, Jonathan; Tanaka, Yujiro

    2016-01-01

    A majority of facioscapulohumeral muscular dystrophy (FSHD) is caused by contraction of macrosatellite repeats called D4Z4 that are located in the subtelomeric region of human chromosome 4q35. Sequencing the FSHD locus has been technically challenging due to its long size and nearly identical nature of repeat elements. Here we report sequencing and partial assembly of a BAC clone carrying an entire FSHD locus by a single molecule real time (SMRT) sequencing technology which could produce long reads up to about 18 kb containing D4Z4 repeats. De novo assembly by Hierarchical Genome Assembly Process 1 (HGAP.1) yielded a contig of 41 kb containing all but a part of the most distal D4Z4 element. The validity of the sequence model was confirmed by an independent approach employing anchored multiple sequence alignment by Kalign using reads containing unique flanking sequences. Our data will provide a basis for further optimization of sequencing and assembly conditions of D4Z4. PMID:27002334

  17. Filling in the Gap of Human Chromosome 4: Single Molecule Real Time Sequencing of Macrosatellite Repeats in the Facioscapulohumeral Muscular Dystrophy Locus.

    PubMed

    Morioka, Masaki Suimye; Kitazume, Miwako; Osaki, Ken; Wood, Jonathan; Tanaka, Yujiro

    2016-01-01

    A majority of facioscapulohumeral muscular dystrophy (FSHD) is caused by contraction of macrosatellite repeats called D4Z4 that are located in the subtelomeric region of human chromosome 4q35. Sequencing the FSHD locus has been technically challenging due to its long size and nearly identical nature of repeat elements. Here we report sequencing and partial assembly of a BAC clone carrying an entire FSHD locus by a single molecule real time (SMRT) sequencing technology which could produce long reads up to about 18 kb containing D4Z4 repeats. De novo assembly by Hierarchical Genome Assembly Process 1 (HGAP.1) yielded a contig of 41 kb containing all but a part of the most distal D4Z4 element. The validity of the sequence model was confirmed by an independent approach employing anchored multiple sequence alignment by Kalign using reads containing unique flanking sequences. Our data will provide a basis for further optimization of sequencing and assembly conditions of D4Z4. PMID:27002334

  18. Refining the localization of the PKD2 locus on chromosome 4q by linkage analysis in Spanish families with autosomal dominant polycystic kidney disease type 2

    SciTech Connect

    San Millan, J.L.; Viribay, M.; Peral, B.; Moreno, F.; Martinez, I.; Weissenbach, J.

    1995-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder. At least two distinct forms of ADPKD are now well defined. In {approximately}86% of affected European families, a gene defect localized to 16p13.3 was responsible for ADPKD, while a second locus has been recently localized to 4q13-q23 as candidate for the disease in the remaining families. We present confirmation of linkage to microsatellite markers on chromosome 4q in eight Spanish families with ADPKD, in which the disease was not linked to 16p13.3. By linkage analysis with marker D4S423, a maximum lod score of 9.03 at a recombination fraction of .00 was obtained. Multipoint linkage analysis, as well as a study of recombinant haplotypes, placed the PKD2 locus between D4S1542 and D4S1563, thereby defining a genetic interval of {approximately}1 cM. The refined map will serve as a genetic framework for additional genetic and physical mapping of the region and will improve the accuracy of presymptomatic diagnosis of PKD2. 25 refs., 4 figs., 1 tab.

  19. A Novel Locus for Ectodermal Dysplasia of Hair, Nail and Skin Pigmentation Anomalies Maps to Chromosome 18p11.32-p11.31

    PubMed Central

    Habib, Rabia; Ansar, Muhammad; Mattheisen, Manuel; Shahid, Muhammad; Ali, Ghazanfar; Ahmad, Wasim; Betz, Regina C.

    2015-01-01

    Ectodermal dysplasias (EDs) are a large heterogeneous group of inherited disorders exhibiting abnormalities in ectodermally derived appendages such as hair, nails, teeth and sweat glands. EDs associated with reticulated pigmentation phenotype are rare entities for which the genetic basis and pathophysiology are not well characterized. The present study describes a five generation consanguineous Pakistani family segregating an autosomal recessive form of a novel type of ectodermal dysplasia. The affected members present with sparse and woolly hair, severe nail dystrophy and reticulate skin pigmentation. After exclusion of known gene loci related with other skin disorders, genome-wide linkage analysis was performed using Illumina HumanOmniExpress beadchip SNP arrays. We linked this form of ED to human chromosome 18p11.32-p11.31 flanked by the SNPs rs9284390 (0.113Mb) and rs4797100 (3.14 Mb). A maximum two-point LOD score of 3.3 was obtained with several markers along the disease interval. The linkage interval of 3.03 Mb encompassed seventeen functional genes. However, sequence analysis of all these genes did not discover any potentially disease causing-variants. The identification of this novel locus provides additional information regarding the mapping of a rare form of ED. Further research, such as the use of whole-genome sequencing, would be expected to reveal any pathogenic mutation within the disease locus. PMID:26115030

  20. A genome-wide association study identifies a region at chromosome 12 as a potential susceptibility locus for restenosis after percutaneous coronary intervention

    PubMed Central

    Sampietro, M. Lourdes; Trompet, Stella; Verschuren, Jeffrey J.W.; Talens, Rudolf P.; Deelen, Joris; Heijmans, Bastiaan T.; de Winter, Robbert J.; Tio, Rene A.; Doevendans, Pieter A.F.M.; Ganesh, Santhi K.; Nabel, Elizabeth G.; Westra, Harm-Jan; Franke, Lude; van den Akker, Erik B.; Westendorp, Rudi G.J.; Zwinderman, Aeilko H.; Kastrati, Adnan; Koch, Werner; Slagboom, P.Eline; de Knijff, Peter; Jukema, J. Wouter

    2011-01-01

    Percutaneous coronary intervention (PCI) has become an effective therapy to treat obstructive coronary artery diseases (CAD). However, one of the major drawbacks of PCI is the occurrence of restenosis in 5–25% of all initially treated patients. Restenosis is defined as the re-narrowing of the lumen of the blood vessel, resulting in renewed symptoms and the need for repeated intervention. To identify genetic variants that are associated with restenosis, a genome-wide association study (GWAS) was conducted in 295 patients who developed restenosis (cases) and 571 who did not (controls) from the GENetic Determinants of Restenosis (GENDER) study. Analysis of ∼550 000 single nucleotide polymorphisms (SNPs) in GENDER was followed by a replication phase in three independent case–control populations (533 cases and 3067 controls). A potential susceptibility locus for restenosis at chromosome 12, including rs10861032 (Pcombined = 1.11 × 10−7) and rs9804922 (Pcombined = 1.45 × 10−6), was identified in the GWAS and replication phase. In addition, both SNPs were also associated with coronary events (rs10861032, Padditive = 0.005; rs9804922, Padditive = 0.023) in a trial based cohort set of elderly patients with (enhanced risk of) CAD (PROSPER) and all-cause mortality in PROSPER (rs10861032, Padditive = 0.007; rs9804922, Padditive = 0.013) and GENDER (rs10861032, Padditive = 0.005; rs9804922, Padditive = 0.023). Further analysis suggests that this locus could be involved in regulatory functions. PMID:21878436

  1. Familial bone marrow monosomy 7. Evidence that the predisposing locus is not on the long arm of chromosome 7.

    PubMed Central

    Shannon, K M; Turhan, A G; Chang, S S; Bowcock, A M; Rogers, P C; Carroll, W L; Cowan, M J; Glader, B E; Eaves, C J; Eaves, A C

    1989-01-01

    Loss of expression of a tumor-suppressing gene is an attractive model to explain the cytogenetic and epidemiologic features of cases of myelodysplasia and acute myelogenous leukemia (AML) associated with bone marrow monosomy 7 or partial deletion of the long arm (7q-). We used probes from within the breakpoint region on 7q-chromosomes (7q22-34) that detect restriction fragment length polymorphisms (RFLPs) to investigate three families in which two siblings developed myelodysplasia with monosomy 7. In the first family, probes from the proximal part of this region identified DNA derived from the same maternal chromosome in both leukemias. The RFLPs in these siblings diverged at the more distal J3.11 marker due to a mitotic recombination in one patient, a result that suggested a critical region on 7q proximal to probe J3.11. Detailed RFLP mapping of the implicated region was then performed in two additional unrelated pairs of affected siblings. In these families, DNA derived from different parental chromosome 7s was retained in the leukemic bone marrows of the siblings. We conclude that the familial predisposition to myelodysplasia is not located within a consistently deleted segment on the long arm of chromosome 7. These data provide evidence implicating multiple genetic events in the pathogenesis of myelodysplasia seen in association with bone marrow monosomy 7 or 7q-. Images PMID:2569483

  2. Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett’s esophagus

    PubMed Central

    2012-01-01

    Barrett’s Esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia. Barrett’s Esophagus strongly predisposes to esophageal adenocarcinoma (EAC), a tumour with a very poor prognosis. We have undertaken the first genome-wide association study on Barrett’s Esophagus, comprising 1,852 UK cases and 5,172 UK controls in discovery and 5,986 cases and 12,825 controls in the replication. Two regions were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10−9, OR(95%CI) =1.21(1.13-1.28)) and chromosome 16q24, rs9936833 (Pcombined=2.74×10−10, OR(95%CI) =1.14(1.10-1.19)). The top SNP on chromosome 6p21 is within the major histocompatibility complex, and the closest protein-coding gene to rs9936833 on chromosome 16q24 is FOXF1, which is implicated in esophageal development and structure. We found evidence that the genetic component of Barrett’s Esophagus is mediated by many common variants of small effect and that SNP alleles predisposing to obesity also increase risk for Barrett’s Esophagus. PMID:22961001

  3. A structural locus for coagulation factor XIIIA (F13A) is located distal to the HLA region on chromosome 6p in man.

    PubMed

    Olaisen, B; Gedde-Dahl, T; Teisberg, P; Thorsby, E; Siverts, A; Jonassen, R; Wilhelmy, M C

    1985-01-01

    Linkage between the locus for coagulation factor XIIIA (F13A) and HLA-region genes has been revealed during a linkage study between F13A and approximately 40 other polymorphic marker genes. In males, the maximum lod score between F13A and HLA-region genes (HLA-A, -C, -B, -DR; C4A, -B; Bf; and/or C2) is 7.60 at theta 1 = .18. To GLO, the maximum lod score is 2.37 at theta 1 = .19; to PGM3, .22 at theta 1 = .35. Female data indicate a clear sex difference in recombination frequency between F13A and HLA. The present findings, in combination with earlier knowledge of PGM3/GLO/HLA localization and gene distances, show that F13A is distal to HLA on the short arm of chromosome 6 in man. It is thus likely that by including FXIIIA typing in linkage studies, the whole male 6p is within mapping distance of highly polymorphic, classical marker genes. Earlier findings that the Hageman factor gene (F12) is located in the same chromosomal region may indicate the presence of a coagulation factor gene cluster in this region.

  4. A structural locus for coagulation factor XIIIA (F13A) is located distal to the HLA region on chromosome 6p in man.

    PubMed Central

    Olaisen, B; Gedde-Dahl, T; Teisberg, P; Thorsby, E; Siverts, A; Jonassen, R; Wilhelmy, M C

    1985-01-01

    Linkage between the locus for coagulation factor XIIIA (F13A) and HLA-region genes has been revealed during a linkage study between F13A and approximately 40 other polymorphic marker genes. In males, the maximum lod score between F13A and HLA-region genes (HLA-A, -C, -B, -DR; C4A, -B; Bf; and/or C2) is 7.60 at theta 1 = .18. To GLO, the maximum lod score is 2.37 at theta 1 = .19; to PGM3, .22 at theta 1 = .35. Female data indicate a clear sex difference in recombination frequency between F13A and HLA. The present findings, in combination with earlier knowledge of PGM3/GLO/HLA localization and gene distances, show that F13A is distal to HLA on the short arm of chromosome 6 in man. It is thus likely that by including FXIIIA typing in linkage studies, the whole male 6p is within mapping distance of highly polymorphic, classical marker genes. Earlier findings that the Hageman factor gene (F12) is located in the same chromosomal region may indicate the presence of a coagulation factor gene cluster in this region. Images Fig. 1 PMID:2858156

  5. Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis

    SciTech Connect

    Okita, Kohei; Tokino, Takashi; Nishimori, Hiroyuki

    1996-04-15

    Carnitine is an essential cofactor for oxidation of mitochondrial fatty acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage myopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele mapped to mouse chromosome 11. As a step toward identifying the gene responsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (defined by markers D11Mit24, D11Mit111,D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38. Our results implied that the jvs gene can be sought on mouse chromosome 11 within a genetic distance no greater than about 1.6 cM. 21 refs., 2 figs.

  6. Primary mediastinal (thymic) large B-cell lymphoma with a der(14)t(8;14)(q24;q32) and a translocation of MYC to the derivative chromosome 14 with a deleted IgH locus.

    PubMed

    Stejskalova, Eva; Jarosova, Marie; Kabickova, Edita; Smelhaus, Vratislav; Mrhalova, Marcela; Kodet, Roman

    2006-10-15

    We report a case of primary mediastinal (thymic) large B-cell lymphoma (PMBL) with an initial karyotype containing numerical chromosomal aberrations: +X, +9, +12, +21, and a novel translocation t(2;11)(q?31; q23 approximately 24) with a duplication of the derivative chromosome 11. Subsequent multicolor fluorescence in situ hybridization (M-FISH) analysis revealed a der(14)t(8;14)(q24;q32). Further analysis using fluorescence in situ hybridization (FISH) with locus-specific probes revealed loss of the entire IgH locus from the der(14)t(8;14) and relocation of MYC to this derivative chromosome 14. Our data show definitively the existence of the t(8;14) in PMBL, previously only suspected. This finding supplies additional evidence that a translocation-mediated MYC activation may be an important event in the pathogenesis of this unique lymphoma. PMID:17011988

  7. Frequent deletion of the CDKN2A locus in chordoma: analysis of chromosomal imbalances using array comparative genomic hybridisation

    PubMed Central

    Hallor, K H; Staaf, J; Jönsson, G; Heidenblad, M; Vult von Steyern, F; Bauer, H C F; IJszenga, M; Hogendoorn, P C W; Mandahl, N; Szuhai, K; Mertens, F

    2007-01-01

    The initiating somatic genetic events in chordoma development have not yet been identified. Most cytogenetically investigated chordomas have displayed near-diploid or moderately hypodiploid karyotypes, with several numerical and structural rearrangements. However, no consistent structural chromosome aberration has been reported. This is the first array-based study characterising DNA copy number changes in chordoma. Array comparative genomic hybridisation (aCGH) identified copy number alterations in all samples and imbalances affecting 5 or more out of the 21 investigated tumours were seen on all chromosomes. In general, deletions were more common than gains and no high-level amplification was found, supporting previous findings of primarily losses of large chromosomal regions as an important mechanism in chordoma development. Although small imbalances were commonly found, the vast majority of these were detected in single cases; no small deletion affecting all tumours could be discerned. However, the CDKN2A and CDKN2B loci in 9p21 were homo- or heterozygously lost in 70% of the tumours, a finding corroborated by fluorescence in situ hybridisation, suggesting that inactivation of these genes constitute an important step in chordoma development. PMID:18071362

  8. Identification of Chromosome Segment Substitution Lines of Gossypium barbadense Introgressed in G. hirsutum and Quantitative Trait Locus Mapping for Fiber Quality and Yield Traits.

    PubMed

    Zhai, Huanchen; Gong, Wankui; Tan, Yunna; Liu, Aiying; Song, Weiwu; Li, Junwen; Deng, Zhuying; Kong, Linglei; Gong, Juwu; Shang, Haihong; Chen, Tingting; Ge, Qun; Shi, Yuzhen; Yuan, Youlu

    2016-01-01

    Chromosome segment substitution lines MBI9804, MBI9855, MBI9752, and MBI9134, which were obtained by advanced backcrossing and continuously inbreeding from an interspecific cross between CCRI36, a cultivar of upland cotton (Gossypium hirsutum) as the recurrent parent, and Hai1, a cultivar of sea island cotton (G. barbadense) as the donor parent, were used to construct a multiple parent population of (MBI9804×MBI9855)×(MBI9752×MBI9134). The segregating generations of double-crossed F1 and F2 and F2:3 were used to map the quantitative trait locus (QTL) for fiber quality and yield-related traits. The recovery rate of the recurrent parent CCRI36 in the four parental lines was from 94.3%-96.9%. Each of the parental lines harbored 12-20 introgressed segments from Hai1across 21 chromosomes. The number of introgressed segments ranged from 1 to 27 for the individuals in the three generations, mostly from 9 to 18, which represented a genetic length of between 126 cM and 246 cM. A total of 24 QTLs controlling fiber quality and 11 QTLs controlling yield traits were detected using the three segregating generations. These QTLs were distributed across 11 chromosomes and could collectively explain 1.78%-20.27% of the observed phenotypic variations. Sixteen QTLs were consistently detected in two or more generations, four of them were for fiber yield traits and 12 were for fiber quality traits. One introgressed segment could significantly reduce both lint percentage and fiber micronaire. This study provides useful information for gene cloning and marker-assisted breeding for excellent fiber quality. PMID:27603312

  9. Identification of Chromosome Segment Substitution Lines of Gossypium barbadense Introgressed in G. hirsutum and Quantitative Trait Locus Mapping for Fiber Quality and Yield Traits

    PubMed Central

    Liu, Aiying; Song, Weiwu; Li, Junwen; Deng, Zhuying; Kong, Linglei; Gong, Juwu; Shang, Haihong; Chen, Tingting; Ge, Qun; Shi, Yuzhen; Yuan, Youlu

    2016-01-01

    Chromosome segment substitution lines MBI9804, MBI9855, MBI9752, and MBI9134, which were obtained by advanced backcrossing and continuously inbreeding from an interspecific cross between CCRI36, a cultivar of upland cotton (Gossypium hirsutum) as the recurrent parent, and Hai1, a cultivar of sea island cotton (G. barbadense) as the donor parent, were used to construct a multiple parent population of (MBI9804×MBI9855)×(MBI9752×MBI9134). The segregating generations of double-crossed F1 and F2 and F2:3 were used to map the quantitative trait locus (QTL) for fiber quality and yield-related traits. The recovery rate of the recurrent parent CCRI36 in the four parental lines was from 94.3%–96.9%. Each of the parental lines harbored 12–20 introgressed segments from Hai1across 21 chromosomes. The number of introgressed segments ranged from 1 to 27 for the individuals in the three generations, mostly from 9 to 18, which represented a genetic length of between 126 cM and 246 cM. A total of 24 QTLs controlling fiber quality and 11 QTLs controlling yield traits were detected using the three segregating generations. These QTLs were distributed across 11 chromosomes and could collectively explain 1.78%–20.27% of the observed phenotypic variations. Sixteen QTLs were consistently detected in two or more generations, four of them were for fiber yield traits and 12 were for fiber quality traits. One introgressed segment could significantly reduce both lint percentage and fiber micronaire. This study provides useful information for gene cloning and marker-assisted breeding for excellent fiber quality. PMID:27603312

  10. Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21.

    PubMed

    Piret, Sian E; Danoy, Patrick; Dahan, Karin; Reed, Anita A C; Pryce, Karena; Wong, William; Torres, Rosa J; Puig, Juan G; Müller, Thomas; Kotanko, Peter; Lhotta, Karl; Devuyst, Olivier; Brown, Matthew A; Thakker, Rajesh V

    2011-01-01

    Familial juvenile hyperuricaemic (gouty) nephropathy (FJHN), is an autosomal dominant disease associated with a reduced fractional excretion of urate, and progressive renal failure. FJHN is genetically heterogeneous and due to mutations of three genes: uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1beta (HNF-1β) on chromosomes 16p12, 1q32.1, and 17q12, respectively. However, UMOD, REN or HNF-1β mutations are found in only approximately 45% of FJHN probands, indicating the involvement of other genetic loci in approximately 55% of probands. To identify other FJHN loci, we performed a single nucleotide polymorphism (SNP)-based genome-wide linkage analysis, in six FJHN families in whom UMOD, HNF-1β and REN mutations had been excluded. Parametric linkage analysis using a 'rare dominant' model established linkage in five of the six FJHN families, with a LOD score >+3, at 0% recombination, between FJHN and SNPs at chromosome 2p22.1-p21. Analysis of individual recombinants in two unrelated affected individuals defined a approximately 5.5 Mbp interval, flanked telomerically by SNP RS372139 and centromerically by RS896986 that contained the locus, designated FJHN3. The interval contains 28 genes, and DNA sequence analysis of the most likely candidate, solute carrier family 8 member 1 (SLC8A1), did not identify any abnormalities in the FJHN3 probands. FJHN3 is likely located within a approximately 5.5 Mbp interval on chromosome 2p22.1-p21, and identifying the genetic abnormality will help to further elucidate mechanisms predisposing to gout and renal failure.

  11. Genomewide Linkage Study in 1,176 Affected Sister Pair Families Identifies a Significant Susceptibility Locus for Endometriosis on Chromosome 10q26

    PubMed Central

    Treloar, Susan A.; Wicks, Jacqueline; Nyholt, Dale R.; Montgomery, Grant W.; Bahlo, Melanie; Smith, Vicki; Dawson, Gary; Mackay, Ian J.; Weeks, Daniel E.; Bennett, Simon T.; Carey, Alisoun; Ewen-White, Kelly R.; Duffy, David L.; O’Connor, Daniel T.; Barlow, David H.; Martin, Nicholas G.; Kennedy, Stephen H.

    2005-01-01

    Endometriosis is a common gynecological disease that affects up to 10% of women in their reproductive years. It causes pelvic pain, severe dysmenorrhea, and subfertility. The disease is defined as the presence of tissue resembling endometrium in sites outside the uterus. Its cause remains uncertain despite >50 years of hypothesis-driven research, and thus the therapeutic options are limited. Disease predisposition is inherited as a complex genetic trait, which provides an alternative route to understanding the disease. We seek to identify susceptibility loci, using a positional-cloning approach that starts with linkage analysis to identify genomic regions likely to harbor these genes. We conducted a linkage study of 1,176 families (931 from an Australian group and 245 from a U.K. group), each with at least two members—mainly affected sister pairs—with surgically diagnosed disease. We have identified a region of significant linkage on chromosome 10q26 (maximum LOD score [MLS] of 3.09; genomewide P = .047) and another region of suggestive linkage on chromosome 20p13 (MLS = 2.09). Minor peaks (with MLS > 1.0) were found on chromosomes 2, 6, 7, 8, 12, 14, 15, and 17. This is the first report of linkage to a major locus for endometriosis. The findings will facilitate discovery of novel positional genetic variants that influence the risk of developing this debilitating disease. Greater understanding of the aberrant cellular and molecular mechanisms involved in the etiology and pathophysiology of endometriosis should lead to better diagnostic methods and targeted treatments. PMID:16080113

  12. Genetic mapping of the spinocerebellar ataxia (SCA2) locus on chromosome 12q23-q24.1

    SciTech Connect

    Hernandez, A.; Magarino, C.; Gispert, S.

    1995-01-20

    A refined genetic map of the spinocerebellar ataxia 2 locus was constructed through linkage and haplotype analysis of 11 large pedigrees from the Holguin SCA2 family collective. Three-point analysis makes a localization of the SCA2 mutation in the 6-cM interval D12S84-D12S79 likely. This is consistent with haplotype results indicating a crossover event between two branches of the SCA2 family Rs and placing the mutation on the telomeric side of D12S84. The microsatellite D12S105 within this interval shows a peak two-point lod score of Z = 16.14 at {theta} = 0.00 recombination and complete linkage disequilibrium among affected individuals. These data together with the observation of a common disease haplotype among all family ancestors support the notion of an SCA2 founder effect in Holguin province. 17 refs., 2 figs., 1 tab.

  13. Further evidence for a locus for autosomal dominant juvenile glaucoma on chromosome 1q and evidence for genetic heterogeneity

    SciTech Connect

    Wiggs, J.; Paglinauan, C.; Stawski, S.

    1994-09-01

    Glaucoma is a term used to describe a group of disorders which have in common a characteristic degeneration of the optic nerve associated with typical visual field defects and usually associated with elevated intraocular pressure. Two percent of white Americans and 6-10% of black Americans are affected by the disease. Compelling data indicate that susceptibility to many types of glaucoma is inherited. Hereditary juvenile glaucoma is one form of glaucoma that develops in children and is inherited as an autosomal dominant trait with high penetrance. Using a single large Caucasian pedigree affected with autosomal dominant juvenile glaucoma, Sheffield discovered positive linkage to a group of markers that map to a 30 cM region on the long arm of chromosome 1 (1q21-q31). We have subsequently identified three unrelated Caucasian pedigrees affected with autosomal dominant juvenile glaucoma that also demonstrate linkage to this region on chromosome 1, with the highest combined lod score of 5.12 at theta = .05 for marker D1S218. The identification of critical recombinant individuals in our three pedigrees has allowed us to further localize the disease gene to a 12 cM region between markers D1S242 and D1S431. In addition, we have identified several pedigrees which do not demonstrate linkage to chromosome 1q, including a black family affected with autosomal dominant juvenile glaucoma that is indistinguishable clinically from the disorder affecting the caucasian pedigrees and three pedigrees affected with pigmentary dispersion syndrome, a form of glaucoma that also affects the juvenile population and is also inherited as an autosomal dominant trait. These findings provide evidence for genetic heterogeneity in juvenile glaucoma.

  14. Genetic, physical and functional analysis of the ataxia-telangiectasia locus on chromosome 11q22-23

    SciTech Connect

    Shiloh, Y.; Ziv, Y.; Savitski, K.

    1994-09-01

    Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder featuring cerebellar degeneration, immunodeficiency, chromosomal instability, cancer susceptibility, and radiosensitivity. Four complementation groups have been observed in A-T. The two major groups, A and C, were localized to chromosome 11q22-23, and the other two, D and E, may map to the same chromosomal region. We developed an integrated system of positional and complementation cloning to identify the A-T gene(s). The A-T region was saturated with microsatellite markers by physically mapping markers generated at random by other labs and by identifying new polymorphic CA-repeats in YAC clones obtained from this region. According to recent linkage data based on these markers and linkage disequilibrium analysis in Moroccan Jewish A-T patients, the A-T(A) and A-T(C) mutations are contained within a 2 Mb interval between D11S1819 and D11S1960. This interval was cloned in YAC and cosmid contigs, and transcribed sequences were identified using the following methods: screening of cDNA libraries using cosmid clones; magnetic bead capture using YAC and cosmid clones; direct selection of cDNA clones using YAC clones immobilized on a solid matrix; and 3{prime} exon trapping. Preliminary results indicate that the A-T region is rich in transcribed sequences. Structural and functional analysis of these genes is being carried out by sequence analysis, by physical mapping using the cosmid contigs, and by testing their ability to complement the radiomimetic sensitivity of A-T cells.

  15. A yeast artificial chromosome (YAC) contig encompassing the critical region of the X-linked lymphoproliferative disease (XLP) locus.

    PubMed

    Lanyi, A; Li, B; Li, S; Talmadge, C B; Brichacek, B; Davis, J R; Kozel, B A; Trask, B; van den Engh, G; Uzvolgyi, E; Stanbridge, E J; Nelson, D L; Chinault, C; Heslop, H; Gross, T G; Seemayer, T A; Klein, G; Purtilo, D T; Sumegi, J

    1997-01-01

    X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability to Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia, or malignant lymphoma. Initially the XLP gene was assigned to a 10-cM region in Xq25 between DXS42 and DXS37. Subsequently, an interstitial, cytogenetically visible deletion in Xq25 was identified in one XLP family, 43. In this study we estimated the deletion in XLP patient 43-004 by dual-laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mb of DNA sequence. From a human chromosome Xq25-specific yeast artificial chromosome (YAC) sublibrary, five YACs containing DNA sequences deleted in patient 43-004 have been isolated. Sequence-tagged sites (STSs) from these YACs have been used to identify interstitial deletions in unrelated XLP patients. Three more families with interstitial deletions were found. Two of the patients (63-003 and 73-032) carried an interstitial deletion of 3.0 Mb overlapping the 43-004 deletion. In one XLP patient (30-011) who exhibited the characteristic postinfectious mononucleosis phenotype of XLP with hypogammaglobulinemia and malignant lymphoma, a deletion of approximately 250 kb was detected overlapping the deletion detected in patients 43-004, 63-003, and 73-032. A YAC contig of 2.2 Mb spanning the XLP critical region, whose orientation on chromosome X was determined by double-color fluorescence in situ hybridization and which consists of 15 overlapping YAC clones, has been constructed. A detailed restriction enzyme map of the region has been constructed. YAC insert sizes were determined by counter-clamped homogenous electric field gel electrophoresis. Chimerism of YACs was determined by FISH and restriction mapping. On the basis of lambda subclones, YAC end-derived plasmids, and STSs with an average spacing of 100 kb, a long-range physical map was constructed using 5 rare-cutter restriction

  16. Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion.

    PubMed Central

    Kant, J A; Fornace, A J; Saxe, D; Simon, M I; McBride, O W; Crabtree, G R

    1985-01-01

    Human fibrinogen cDNA probes for the alpha-, beta-, and gamma-polypeptide chains have been used to isolate the corresponding genes from human genomic libraries. There is a single copy of each gene. Restriction endonuclease analysis of isolated genomic clones and human genomic DNA indicates that the human alpha-, beta-, and gamma-fibrinogen genes are closely linked in a 50-kilobase region of a single human chromosome: the alpha-gene in the middle flanked by the beta-gene on one side and the gamma-gene on the other. The alpha- and gamma-chain genes are oriented in tandem and transcribed toward the beta-chain gene. The beta-chain gene is transcribed from the opposite DNA strand toward the gamma- and alpha-chain genes. The three genes have been localized to the distal third of the long arm of chromosome 4, bands q23-q32, by in situ hybridization with fibrinogen cDNAs and by examination of DNA from multiple rodent-human somatic cell hybrids. Alternative explanations for the present arrangement of the three fibrinogen genes involve either a three-step mechanism with inversion of the alpha/gamma-region or a two-step mechanism involving remote transposition and inversion. The second more simple mechanism has a precedent in the origin of repeated regions of the fibrinogen and immunoglobulin genes. Images PMID:2986113

  17. High-resolution meiotic and physical mapping of the Best`s vitelliform macular dystrophy (VMD2) locus to pericentromeric chromosome 11

    SciTech Connect

    Weber, B.H.F.; Vogt, G.; Walker, D.

    1994-09-01

    Vitelliform macular dystrophy, also known as Best`s disease, is a juvenile-onset macular degeneration with autosomal dominant inheritance. It is characterized by well-demarcated accumulation of lipofuscin-like material within and beneath the retinal pigment epithelium (RPE) and classically results in an egg yolk-like appearance of the macula. Typically, carriers of the disease gene show a specific electrophysiological sign which can be detected by electrooculography (EOG). The EOG measures a standing potential between the cornea and the retina which is primarily generated by the RPE. The histopathological findings as well as the EOG abnormalities suggest that Best`s disease is a generalized disorder of the RPE. The basic biochemical defect is still unknown. As a first step in the positional cloning of the defective gene, the Best`s disease locus was mapped to chromosome 11 between markers at D11S871 and INT2. Subsequently, his region was refined to a 3.7 cM interval flanked by loci D11S903 and PYGM. To further narrow the D11S903-PYGM interval and to obtain an estimate of the physical size of the minimal candidate region, we used a combination of high-resolution PCR hybrid mapping and analysis of recombinant Best`s disease chromosomes. We identified six markers from within the D11S903-PYGM interval that show no recombination with the defective gene in three multigeneration Best`s disease pedigrees. Our hybrid panel localizes these markers on either side of the centromere on chromosome 11. The closest markers flanking the disease gene are at D11S986 in band p12-11.22 and at D11S480 in band q13.2-13.3. Our study demonstrates that the physical size of the Best`s disease region is exceedingly larger than was previously estimated from the genetic data due to the proximity of the defective gene to the centromere of chromosome 11.

  18. Two Functional Copies of the DGCR6 Gene Are Present on Human Chromosome 22q11 Due to a Duplication of an Ancestral Locus

    PubMed Central

    Edelmann, Lisa; Stankiewicz, Pavel; Spiteri, Elizabeth; Pandita, Raj K.; Shaffer, Lisa; Lupski, James; Morrow, Bernice E.

    2001-01-01

    The DGCR6 (DiGeorge critical region) gene encodes a putative protein with sequence similarity to gonadal (gdl), a Drosophila melanogaster gene of unknown function. We mapped the DGCR6 gene to chromosome 22q11 within a low copy repeat, termed sc11.1a, and identified a second copy of the gene, DGCR6L, within the duplicate locus, termed sc11.1b. Both sc11.1 repeats are deleted in most persons with velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), and they map immediately adjacent and internal to the low copy repeats, termed LCR22, that mediate the deletions associated with VCFS/DGS. We sequenced genomic clones from both loci and determined that the putative initiator methionine is located further upstream than originally described, but in a position similar to the mouse and chicken orthologs. DGCR6L encodes a highly homologous, functional copy of DGCR6, with some base changes rendering amino acid differences. Expression studies of the two genes indicate that both genes are widely expressed in fetal and adult tissues. Evolutionary studies using FISH mapping in several different species of ape combined with sequence analysis of DGCR6 in a number of different primate species indicate that the duplication is at least 12 million years old and may date back to before the divergence of Catarrhines from Platyrrhines, 35 mya. These data suggest that there has been selective evolutionary pressure toward the functional maintenance of both paralogs. Interestingly, a full-length HERV-K provirus integrated into the sc11.1a locus after the divergence of chimpanzees and humans. PMID:11157784

  19. Targeted mapping of quantitative trait locus regions for rhizomatousness in chromosome SBI-01 and analysis of overwintering in a Sorghum bicolor × S. propinquum population.

    PubMed

    Washburn, Jacob D; Murray, Seth C; Burson, Byron L; Klein, Robert R; Jessup, Russell W

    2013-01-01

    While rhizome formation is intimately associated with perennialism and the derived benefit of sustainability, the introduction of this trait into temperate-zone adapted Sorghum cultivars requires precise knowledge of the genetics conditioning this trait in order to minimize the risk of weediness (e.g., Johnsongrass, S. halepense) while maximizing the productivity of perennial sorghum. As an incremental step towards dissecting the genetics of perennialism, a segregating F4 heterogeneous inbred family derived from a cross between S. bicolor and S. propinquum was phenotyped in both field and greenhouse environments for traits related to over-wintering and rhizome formation. An unseasonably cold winter in 2011 provided high selection pressure, and hence 74.8 % of the population did not survive. This severe selection pressure for cold tolerance allowed the resolution of two previously unidentified over-wintering quantitative trait locus (QTL) and more powerful correlation models than previously reported. Conflicting with previous reports, a maximum of 33 % of over-wintering variation could be explained by above-ground shoot formation from rhizomes; however, every over-wintering plant exhibited rhizome growth. Thus, while rhizome formation is required for over-wintering, other factors also determine survival in this interspecific population. The fine mapping of a previously reported rhizome QTL on sorghum chromosome SBI-01 was conducted by targeting this genomic region with additional simple sequence repeat markers. Fine mapping reduced the 2-LOD rhizome QTL interval from ~59 to ~14.5 Mb, which represents a 75 % reduction in physical distance and a 53 % reduction in the number of putative genes in the locus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11032-012-9778-8) contains supplementary material, which is available to authorized users.

  20. Genetic linkage mapping for a susceptibility locus to bipolar illness: Chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and Xpter

    SciTech Connect

    Detera-Wadleigh, S.D.; Hseih, W.T.; Goldin, L.R.

    1994-09-15

    We are conducting a genome search for a predisposing locus to bipolar (manic-depressive) illness by genotyping 21 moderate-sized pedigrees. We report linkage data derived from screening marker loci on chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and the pseudoautosomal region at Xpter. To analyze for linkage, two-point marker to illness lod scores were calculated under a dominant model with either 85% or 50% maximum penetrance and a recessive model with 85% maximum penetrance, and two affection status models. Under the dominant high penetrance model the cumulative lod scores in the pedigree series were less than -2 at {theta} = 0.01 in 134 of 142 loci examined, indicating that if the disease is genetically homogeneous, linkage could be excluded in these marker regions. Similar results were obtained using the other genetic models. Heterogeneity analysis was conducted when indicated, but no evidence for linkage was found. In the course of mapping we found a positive total lod score greater than +3 at the D7S78 locus at {theta} = 0.01 under a dominant, 50% penetrance model. The lod scores for additional markers within the D7S78 region failed to support the initial finding, implying that this was a spurious positive. Analysis with affected pedigree member method for COL1A2 and D7S78 showed no significance for linkage, but for PLANH1, at the weighting functions f(p)=1 and f(p)=1/sqrt(p), borderline P values of 0.036 and 0.047 were obtained. We also detected new polymorphisms at the mineralo-corticoid receptor (MLR) and calmodulin II (CALMII) genes. These genes were genetically mapped and under affection status model 2 and a dominant, high penetrance mode of transmission the lod scores of {le}2 at {theta} = 0.01 were found. 39 refs., 2 figs., 12 tabs.

  1. Evidence for an association between nonsyndromic cleft lip with or without cleft palate and a gene located on the long arm of chromosome 4

    SciTech Connect

    Mitchell, L.E.; Healey, S.C.; Chenevix-Trench, G. |

    1995-11-01

    Recent studies suggest that the familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL{+-}P) is likely to be attributable to the effects of several susceptibility loci, acting in a multiplicative fashion. Two potential CL{+-}P susceptibility loci (CSL), transforming growth factor alpha (TGFA) and retinoic acid receptor (RARA), have been identified through association studies. In addition, recent evidence of linkage between CL{+-}P and two markers (D4S175 and D4S192) in the region 4q25-4q31.3 raised the possibility that a CSL, with a larger effect than either TGFA or RARA, may reside within this region of the human genome. The present analyses were undertaken to determine whether D4S175 or D4S192 is significantly associated with CL{+-}P in a sample of unrelated patients that have previously provided evidence of associations between CL{+-}P and both TGFA and RARA. The results of these analyses provide further, tentative, evidence for the presence of a CSL locus on the long arm of chromosome 4 and help to refine the location of this locus in the region of D4S175 and D4S192. 28 refs., 4 tabs.

  2. Linkage analysis of a new locus for autosomal recessive retinitis pigmentosa (arRP) on chromosome 6p

    SciTech Connect

    Shugart, Y.Y.; Knowles, J.A.; Banerjee, P.

    1994-09-01

    We report the localization of the arRP gene segregating in a large kindred from the Dominican Republic and the progress in refining the arRP region. The arRP gene in this family was found to be closely linked to markers D6S291, D6S273 with lod scores of 6.75, 3.08 at {theta}=0, 0.08, respectively. Since it was suggested that mutant peripherin causes arRP on 6p, we typed marker RDS1 at the peripherin-rds locus and detected four recombinants. More markers have been typed to further refine the location of arRP. Lod scores of 5.31. 5.89 and 2.05 were obtained with D6S439, UT722 and D6S426 at {theta}=0, 0, and 0.14, respectively. Some of the new markers were not included in the Genethon map, thus we used the CEPH (V7.0) data to order markers D6S273, D6S439, UT722, D6S426 and to estimate the recombination fractions as well as the ratios of female to male map distance. The best supported order is: D6S273 - D6S439 - D6S291 - UT722 - D6S426. Multipoint analyses were performed with the markers D6S273 - ({theta}{sub m}=0.0-21) - D6S439 - ({theta}{sub m}=0.066) - D6S426 with a constant sex ratio of 2.749. A maximum lod score of 9.74 was obtained at the marker D6S439. In conclusion, the most likely location for the arRP gene in the Dominican pedigree is approximately 20 centimorgans (cM) telomeric from peripherin.

  3. The Cnes2 locus on mouse chromosome 17 regulates host defense against cryptococcal infection through pleiotropic effects on host immunity.

    PubMed

    Shourian, Mitra; Flaczyk, Adam; Angers, Isabelle; Mindt, Barbara C; Fritz, Jörg H; Qureshi, Salman T

    2015-12-01

    The genetic basis of natural susceptibility to progressive Cryptococcus neoformans infection is not well understood. Using C57BL/6 and CBA/J inbred mice, we previously identified three chromosomal regions associated with C. neoformans susceptibility (Cnes1, Cnes2, and Cnes3). To validate and characterize the role of Cnes2 during the host response, we constructed a congenic strain on the C57BL/6 background (B6.CBA-Cnes2). Phenotypic analysis of B6.CBA-Cnes2 mice 35 days after C. neoformans infection showed a significant reduction of fungal burden in the lungs and spleen with higher pulmonary expression of gamma interferon (IFN-γ) and interleukin-12 (IL-12), lower expression of IL-4, IL-5, and IL-13, and an absence of airway epithelial mucus production compared to that in C57BL/6 mice. Multiparameter flow cytometry of infected lungs also showed a significantly higher number of neutrophils, exudate macrophages, CD11b(+) dendritic cells, and CD4(+) cells in B6.CBA-Cnes2 than in C57BL/6 mice. The activation state of recruited macrophages and dendritic cells was also significantly increased in B6.CBA-Cnes2 mice. Taken together, these findings demonstrate that the Cnes2 interval is a potent regulator of host defense, immune responsiveness, and differential Th1/Th2 polarization following C. neoformans infection.

  4. Linkage of a locus for carbohydrate-deficient glycoprotein syndrome type I (CDG1) to chromosome 16p-markers

    SciTech Connect

    Martinsson, T.; Bjursell, C.; Wahlstroem, J.

    1994-09-01

    Carbohydrate-deficient glycoprotein syndrome type I is a multisystem disease with early severe nervous system involvement. The disease, which is inherited as a recessive autosomal trait, is biochemically characterized by complex defects in the terminal carbohydrate residues of a number of serum glycoproteins. This can be most readily detected in transferrin. A whole genome scan was initiated in order to try localizing the gene (CDG1) with linkage technique. We therefore analyzed 25 CDG1-pedigrees with several highly polymorphic microsatellite markers and after exclusion of about 30% of the genome, linkage was detected with markers located in chromosome region 16p. The lod score (Zmax) was above 8 (theta=0.00) for several markers in the region. In order to further sublocalize the CDG1 gene, recombination and linkage disequilibrium analyses were performed. Recombination events in some pedigrees indicated that the CDG1 gene is located in a 13 cM interval between microsatellite markers D16S406 and D16S500. Furthermore, allelic association was shown for marker D16S406, indicating that the CDG1 gene is located close to this. No heterogeneity could be detected in the European family material tested by us.

  5. Localization of the congenital dyserythropoietic anemia II locus to chromosome 20q11.2 by genomewide search.

    PubMed Central

    Gasparini, P; Miraglia del Giudice, E; Delaunay, J; Totaro, A; Granatiero, M; Melchionda, S; Zelante, L; Iolascon, A

    1997-01-01

    Congenital dyserythropoietic anemias (CDA) are genetic disorders characterized by anemia and ineffective erythropoiesis. Three main types of CDA have been distinguished: CDA I and CDA III, whose loci have been already mapped, and CDA II (MIM 224100), the most frequent among CDAs, which is transmitted as an autosomal recessive trait and is known also as "HEMPAS" (hereditary erythroblast multinuclearity with positive acidified serum). We have recruited a panel of well-characterized CDA II families and have used them to search for the CDA II gene by linkage analysis. After the exclusion of three candidate genes, we ob-tained conclusive evidence for linkage of CDA II to microsatellite markers on the long arm of chromosome 20 (20q11.2). A maximum two-point LOD score of 5.4 at a recombination fraction of .00 was obtained with marker D20S863. Strong evidence of allelic association with the disease was detected with the same marker. Some recombinational events established a maximum candidate interval of approximately 5 cM. PMID:9345103

  6. A combined analysis of D22S278 marker alleles in affected sib-pairs: Support for a susceptibility locus for schizophrenia at chromosome 22q12

    SciTech Connect

    Gill, M.; Vallada, H.; Collier, D.

    1996-02-16

    Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets. Using the affected sib-pair method as implemented by the program ESPA, the combined dataset showed 252 alleles shared compared with 188 alleles not shared (chi-square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib-pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi-square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib-pair analysis was used. These results indicate that there may be a susceptibility locus for schizophrenia at 22q12. 27 refs., 3 tabs.

  7. A new autosomal recessive nonsyndromic hearing impairment locus DFNB96 on chromosome 1p36.31-p36.13.

    PubMed

    Ansar, Muhammad; Lee, Kwanghyuk; Naqvi, Syed Kamran-Ul-Hassan; Andrade, Paula B; Basit, Sulman; Santos-Cortez, Regie Lyn P; Ahmad, Wasim; Leal, Suzanne M

    2011-12-01

    A novel locus for autosomal recessive nonsyndromic hearing impairment (ARNSHI), DFNB96, was mapped to the 1p36.31-p36.13 region. A whole-genome linkage scan was performed using DNA samples from a consanguineous family from Pakistan with ARNSHI. A maximum two-point logarithm of odds (LOD) score of 3.2 was obtained at marker rs8627 (chromosome 1: 8.34 Mb) at θ=0 and a significant maximum multipoint LOD score of 3.8 was achieved at 15 contiguous markers from rs630075 (9.3 Mb) to rs10927583 (15.13 Mb). The 3-unit support interval and the region of homozygosity were both delimited by markers rs3817914 (6.42 Mb) and rs477558 (18.09 Mb) and contained 11.67 Mb. Of the 125 genes within the DFNB96 interval, the previously identified ARNSHI gene for DFNB36, ESPN, and two genes that cause Bartter syndrome, CLCNKA and CLCNKB, were sequenced, but no potentially causal variants were identified.

  8. A novel autosomal recessive non-syndromic hearing impairment locus (DFNB47) maps to chromosome 2p25.1-p24.3

    PubMed Central

    Hassan, Muhammad Jawad; Santos, Regie Lyn P.; Rafiq, Muhammad Arshad; Chahrour, Maria H.; Pham, Thanh L.; Wajid, Muhammad; Hijab, Nadine; Wambangco, Michael; Lee, Kwanghyuk; Ansar, Muhammad; Yan, Kai; Ahmad, Wasim; Leal, Suzanne M.

    2010-01-01

    Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for ~75% of cases with a genetic etiology. A novel AR non-syndromic HI locus (DFNB47) was mapped to chromosome 2p25.1-p24.3, in two distantly related Pakistani kindreds. Genome scan and fine mapping were carried out using microsatellite markers. Multipoint linkage analysis resulted in a maximum LOD score of 4.7 at markers D2S1400 and D2S262. The three-unit support interval was bounded by D2S330 and D2S131. The region of homozygosity was found within the three-unit support interval and flanked by markers D2S2952 and D2S131, which corresponds to 13.2 cM according to the Rutgers combined linkage-physical map. This region contains 5.3 Mb according to the sequence-based physical map. Three candidate genes, KCNF1, ID2 and ATP6V1C2 were sequenced, and were found to be negative for functional sequence variants. PMID:16261342

  9. Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity

    PubMed Central

    Whalley, Heather C.; Dimitrova, Rali; Sprooten, Emma; Dauvermann, Maria R.; Romaniuk, Liana; Duff, Barbara; Watson, Andrew R.; Moorhead, Bill; Bastin, Mark; Semple, Scott I.; Giles, Stephen; Hall, Jeremy; Thomson, Pippa; Roberts, Neil; Hughes, Zoe A.; Brandon, Nick J.; Dunlop, John; Whitcher, Brandon; Blackwood, Douglas H. R.; McIntosh, Andrew M.; Lawrie, Stephen M.

    2015-01-01

    Objective Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1) is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11) (q42.1;q14.3). Method Within the original pedigree, we examined the effects of the t(1;11) translocation on white matter integrity, measured by fractional anisotropy (FA). This included family members with (n = 7) and without (n = 13) the translocation, along with a clinical control sample of patients with psychosis (n = 34), and a group of healthy controls (n = 33). Results We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity. Conclusions We demonstrate that the t(1;11) translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis. PMID:26102360

  10. A new approach to the elucidation of complex chromosome rearrangements illustrated by a case of Rieger syndrome.

    PubMed Central

    Ogilvie, C M; Raymond, F L; Harrison, R H; Scriven, P N; Docherty, Z

    1998-01-01

    A patient with a complex chromosome rearrangement and unilateral Rieger syndrome is presented. This rearrangement involves four chromosomes and six breakpoints, one of which is at 4q25, the candidate region for Rieger syndrome. We discuss a novel approach to the elucidation of this case using a multiprobe fluorescence in situ hybridisation method to show rearrangements unpredictable from G banded analysis, and the clear and unambiguous presentation of the karyotype using computer generated colour ideograms. Images PMID:9541109

  11. Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults

    PubMed Central

    Close, James; Game, Laurence; Clark, Barnaby; Bergounioux, Jean; Gerovassili, Ageliki; Thein, Swee Lay

    2004-01-01

    Background Heterocellular hereditary persistence of fetal hemoglobin (HPFH) is a common multifactorial trait characterized by a modest increase of fetal hemoglobin levels in adults. We previously localized a Quantitative Trait Locus for HPFH in an extensive Asian-Indian kindred to chromosome 6q23. As part of the strategy of positional cloning and a means towards identification of the specific genetic alteration in this family, a thorough annotation of the candidate interval based on a strategy of in silico / wet biology approach with comparative genomics was conducted. Results The ~1.5 Mb candidate region was shown to contain five protein-coding genes. We discovered a very large uncharacterized gene containing WD40 and SH3 domains (AHI1), and extended the annotation of four previously characterized genes (MYB, ALDH8A1, HBS1L and PDE7B). We also identified several genes that do not appear to be protein coding, and generated 17 kb of novel transcript sequence data from re-sequencing 97 EST clones. Conclusion Detailed and thorough annotation of this 1.5 Mb interval in 6q confirms a high level of aberrant transcripts in testicular tissue. The candidate interval was shown to exhibit an extraordinary level of alternate splicing – 19 transcripts were identified for the 5 protein coding genes, but it appears that a significant portion (14/19) of these alternate transcripts did not have an open reading frame, hence their functional role is questionable. These transcripts may result from aberrant rather than regulated splicing. PMID:15169551

  12. Candidate-Gene Screening and Association Analysis at the Autism-Susceptibility Locus on Chromosome 16p: Evidence of Association at GRIN2A and ABAT

    PubMed Central

    Barnby, Gabrielle; Abbott, Aaron; Sykes, Nuala; Morris, Andrew; Weeks, Daniel E.; Mott, Richard; Lamb, Janine; Bailey, Anthony J.; Monaco, Anthony P.

    2005-01-01

    Autism is a highly heritable neurodevelopmental disorder whose underlying genetic causes have yet to be identified. To date, there have been eight genome screens for autism, two of which identified a putative susceptibility locus on chromosome 16p. In the present study, 10 positional candidate genes that map to 16p11-13 were examined for coding variants: A2BP1, ABAT, BFAR, CREBBP, EMP2, GRIN2A, MRTF-B, SSTR5, TBX6, and UBN1. Screening of all coding and regulatory regions by denaturing high-performance liquid chromatography identified seven nonsynonymous changes. Five of these mutations were found to cosegregate with autism, but the mutations are not predicted to have deleterious effects on protein structure and are unlikely to represent significant etiological variants. Selected variants from candidate genes were genotyped in the entire International Molecular Genetics Study of Autism Consortium collection of 239 multiplex families and were tested for association with autism by use of the pedigree disequilibrium test. Additionally, genotype frequencies were compared between 239 unrelated affected individuals and 192 controls. Patterns of linkage disequilibrium were investigated, and the transmission of haplotypes across candidate genes was tested for association. Evidence of single-marker association was found for variants in ABAT, CREBBP, and GRIN2A. Within these genes, 12 single-nucleotide polymorphisms (SNPs) were subsequently genotyped in 91 autism trios (one affected individual and two unaffected parents), and the association was replicated within GRIN2A (Fisher's exact test, P<.0001). Logistic regression analysis of SNP data across GRIN2A and ABAT showed a trend toward haplotypic differences between cases and controls. PMID:15830322

  13. A transcription map of the regions surrounding the CSF1R locus on human chromosome 5q31: Candidate genes for diastrophic dysplasia

    SciTech Connect

    Clines, G.; Lovett, M.

    1994-09-01

    Diastrophic dysplasia (DTD) is an autosomal recessive disorder of unknown pathogenesis that is characterized by abnormal skeletal and cartilage growth. Phenotypic characteristics of the disorder include short stature, scoliosis, and deformation of the first metacarpal. The diastrophic dysplasia gene has been localized to chromosome 5q31-33, within {approximately}60 kb of the colony stimulating factor 1 receptor gene (CSF1R). We have used direct cDNA selection to build a transcription map across {approximately}250 kb surrounding and including the CSF1R locus. cDNA pools from human placenta, activated T cells, cerebellum, Hela cells, fetal brain, chondrocytes, chondrosarcomas and osteosarcomas were multiplexed in these selections. After two rounds of selection, an analysis revealed that {approximately}70% of the selected cDNAs were contained within the contig. DNA sequencing and cosmid mapping data from a collection of 310 clones revealed the presence of three new genes in this region that show no appreciable homologies on sequence database searches, as well as cDNA clones from the CSF1R and the PDGFRB loci (another of the known genes in the region). An additional cDNA was found with 100% homology to the gene encoding human ribosomal protein L7 (RPL7). This cDNA comprised {approximately}25% of all selected clones. However, further analysis of the genomic contig revealed the presence of an RPL7 processed pseudogene in very close proximity to the CSF1R and PDGFRB genes. The selection of processed pseudogenes is one previously anticipated artifact of selection metholodolgies, but has not been previously observed. Mutational analysis of the three new genes is underway in diastrophic dysplasia families, as is derivation of full length cDNA clones and the expansion of this detailed transcription map into a larger genomic contig.

  14. The Cmv1 host resistance locus is closely linked to the Ly49 multigene family within the natural killer cell gene complex on mouse chromosome 6

    SciTech Connect

    Forbes, C.A.; Shellam, G.R.; Scalzo, A.A.

    1997-05-01

    Natural killer (NK) cells play important roles in controlling tumor cells and against a range of infectious organisms. Recent studies of mouse NK cell surface receptors, which may be involved in the specificity of NK cells, have shown that many of these molecules are encoded by the Ly49 and Ly55 (Nkrp1) multigene families that map to distal mouse chromosome 6. Also mapping to this NK cell gene complex (NKC) is the resistance locus, Cmv1, which is involved in genetically determined resistance to murine cytomegalovirus (MCMV). The aim of this study was to localize Cmv1 more precisely in relation to other NKC loci by generating a high-resolution genetic map of the region. We have analyzed 1250 backcross mice comprising panels of 700 (BALB/c x C57BL/6J)F{sub 1} X BALB/c and 550 (A/J X C57BL/6J)F{sub 1} X A/J progeny. A total of 25 polymorphic genes or microsatellite markers were analyzed over a region of 10 map units from D6Mit134 to D6Mit59. The Cmv1 phenotypes of mice recombinant in this interval were tested by infection with MCMV. The results obtained indicate that the functionally important NKC region is a tightly linked cluster of loci spanning at least 0.4 map units. Furthermore, Cmv1 maps distal to, but very closely linked to, the Ly49 multigene family (< 0.2 map units), suggesting that MCMV resistance may be conferred by MHC class I-specific NK cell receptors. 49 refs., 4 figs., 1 tab.

  15. Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3

    SciTech Connect

    Bullrich, F.; Fernandes-Alnemri, T.; Litwack, G.

    1996-09-01

    Apoptosis may involve a specialized proteolytic cascade catalyzed by interleukin-1{beta}-converting enzyme-like proteases. We have recently identified three new members of this family (CPP32, MCH2, MCH3) and shown that they play an important role in promoting cell death. Here we report the chromosomal mapping of CPP32 to 4q34, MCH2 to 4q25, and MCH3 to 10q25. 16 refs., 2 figs., 1 tab.

  16. Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning 61 cM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a susceptibility locus in this region

    SciTech Connect

    Elmslie, F.V.; Williamson, M.P.; Rees, M.

    1996-09-01

    Linkage analysis in separately ascertained families of probands with juvenile myoclonic epilepsy (JME) has previously provided evidence both for and against the existence of a locus (designated {open_quotes}EJM1{close_quotes}), on chromosome 6p, predisposing to a trait defined as either clinical JME, its associated electroencephalographic abnormality, or idiopathic generalized epilepsy. Linkage analysis was performed in 19 families in which a proband and at least one first- or two second-degree relatives have clinical JME. Family members were typed for seven highly polymorphic microsatellite markers on chromosome 6p: D6S260, D6S276, D6S291, D6S271, D6S465, D6S257, and D6S254. Pairwise and multipoint linkage analysis was carried out under the assumptions of autosomal dominant inheritance at 70% and 50% penetrance and autosomal recessive inheritance at 70% and 50% penetrance. No significant evidence in favor of linkage to the clinical trait of JME was obtained for any locus. The region formally excluded (LOD score <-2) by using multipoint analysis varies depending on the assumptions made concerning inheritance parameters and the proportion of linked families, {alpha} - that is, the degree of locus heterogeneity. Further analysis either classifying all unaffected individuals as unknown or excluding a subset of four families in which pyknoleptic absence seizures were present in one or more individuals did not alter these conclusions. 24 refs., 4 figs., 1 tab.

  17. Localization of a gene for autosomal dominant Larsen syndrome to chromosome region 3p21.1-14.1 in the proximity of, but distinct from the COL7A1 locus

    SciTech Connect

    Vujic, M.; Hallstensson, K.; Wahlstroem, J.

    1995-11-01

    Larsen syndrome (LS) is a skeletal dysplasia (osteochondrodysplasia) in which multiple dislocations of the large joints are the major feature. Nosology in this group of diseases, which constitutes 8% of Mendelian disorders in man, is primarily based on clinical and radiographic features. Hopes for more accurate classification grounds are currently being met by progress in elucidation of underlying genetic defects. We have performed linkage analysis in a large Swedish kindred with autosomal dominant LS and found the gene (LAR1) to be strongly linked to chromosome 3p markers (Z{sub max} = 13.4 at {theta} = .00). Recombination analysis indicates that the LAR1 locus is located in a region defined distally by D3S1581 and proximally by D3S1600, which cytogenetically maps to chromosome region 3p21.1-14.1. Linkage and recombination analysis of a COL7A1 PvuII intragenic polymorphism versus LS and chromosome 3 markers indicate that COL7A1 is located close to, but distinct from, the LAR1 locus. 33 refs., 6 figs., 3 tabs.

  18. A genetic map of chromosome 20q12-q13. 1: Multiple highly polymorphic microsatellite and RFLP markers linked to the maturity-onset diabetes of the Young (MODY) locus

    SciTech Connect

    Rothschild, C.B.; Akots, G.; Hayworth, R.; Pettenati, M.J.; Rao, P.N.; Wood, P. ); Stolz, F.M.; Hansmann, I. ); Serino, K.; Keith, T.P. ); Fajans, S.S. )

    1993-01-01

    Multiple highly polymorphic markers have been used to construct a genetic map of the q12-q13.1 region of chromosome 20 and to map the location of the maturity-onset diabetes of the young (MODY) locus. The genetic map encompasses 23 cM and includes 11 loci with PIC values >.50, seven of which have PICs >.70. New dinucleotide repeat polymorphisms associated with the D20S17, PPGB, and ADA loci have been identified and mapped. The dinucleotide repeat polymorphisms have increased the PIC of the ADA locus to .89 and, with an additional RFLP at the D20S17 locus, the PIC of the D20S17 locus to .88. The order of the D20S17 and ADA loci determined genetically (cen-ADA-D20S17-qter) was confirmed by multicolor fluorescence in situ hybridization. The previously unmapped PPGB marker is closely linked to D20S17, with a two-point lod score of 50.53 at [cflx [theta

  19. 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.

  20. Linkage analysis of idiopathic generalized epilepsy (IGE) and marker loci on chromosome 6p in families of patients with juvenile myocloni epilepsy: No evidence for an epilepsy locus in the HLA region

    SciTech Connect

    Whitehouse, W.P.; Rees, M.; Curtis, D.; Sundqvist, A.; Parker, K.; Chung, E.; Baralle, D.; Gardiner, R.M.

    1993-09-01

    Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisposing to idiopathic generalized epilepsy (IGE) in the families of patients with juvenile myoclonic epilepsy (JME) has been obtained in two previous studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Family members were typed for eight polymorphic loci on chromosome 6p: F13A, D6889, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise and multipoint linkage analysis was carried out assuming autosomal dominant and autosomal recessive inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained at any locus. Multipoint linkage analysis generated significant exclusion data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assumed. These observations indicate that genetic heterogeneity exists within this epilepsy phenotype. 39 refs., 4 figs., 2 tabs.

  1. Alterations of p16-pRb pathway and chromosome locus 9p21-22 in sporadic invasive breast carcinomas.

    PubMed Central

    Gorgoulis, V. G.; Koutroumbi, E. N.; Kotsinas, A.; Zacharatos, P.; Markopoulos, C.; Giannikos, L.; Kyriakou, V.; Voulgaris, Z.; Gogas, I.; Kittas, C.

    1998-01-01

    The p16-pRb pathway represents a vital cell-cycle checkpoint. In the present study we investigated the alterations of this G1-phase protein pathway using immunohistochemical and molecular methods in a series of 55 breast carcinomas and correlated the findings with clinicopathological features of the patients. Furthermore, we examined its relationship with the status of the chromosomal region 9p21-22 performing a deletion map analysis because there are indications that, in addition to CDKN2 and MTS2/p15(INK4B) tumor suppressor genes (TSGs), this area harbors other TSG(s). Aberrant expression (Ab) of p16 and pRb was observed in 26 (47%) and 16 (29%) of the carcinomas, respectively. A statistical trend pointing out an inverse relationship between p16 and pRb expression was found (p = 0.079). Analysis of the region that encodes for p16 by deletion mapping, a PCR-based methylation assay and PCR-SSCP, revealed that deletions and transcriptional silencing by methylation might represent the main mechanisms of CDKN2/p16(INK4A) inactivation in breast carcinomas. The results of deletion mapping also suggest that another TSG(s) may reside at the 9p21-22 area particularly at the D9S162 loci and that co-deletion of this putative gene with CDKN2/p16(INK4A) may play a role in breast carcinogenesis. In addition, microsatellite instability (MI), a marker of replication error phenotype (RER+), was observed with a frequency of 16% in the area examined and was inversely related with loss of heterozygosity (LOH). Interestingly, most cases with MI at the region encoding for p16 were aggregated in a subgroup of breast carcinomas with no other obvious genetic and/or epigenetic CDKN2/p16(INK4A) alterations. We speculate that there is an additional mechanism of CDKN2/p16(INK4A) inactivation. The relationship of p16 protein level pRb, status, the p16-pRb combined immunoprofiles, and the microsatellite alterations detected at the 9p21-22 locus with the patients' clinicopathological parameters

  2. Genome-wide association study identifies susceptibility loci in IL6, RPS9/LILRB3, and an intergenic locus on chromosome 21q22 in Takayasu’s arteritis

    PubMed Central

    Renauer, Paul; Saruhan-Direskeneli, Guher; Coit, Patrick; Adler, Adam; Aksu, Kenan; Keser, Gokhan; Alibaz-Oner, Fatma; Aydin, Sibel Z.; Kamali, Sevil; Inanc, Murat; Carette, Simon; Cuthbertson, David; Hoffman, Gary S.; Akar, Servet; Onen, Fatos; Akkoc, Nurullah; Khalidi, Nader A.; Koening, Curry; Karadag, Omer; Kiraz, Sedat; Langford, Carol A.; Maksimowicz-McKinnon, Kathleen; McAlear, Carol A.; Ozbalkan, Zeynep; Ates, Askin; Karaaslan, Yasar; Duzgun, Nursen; Monach, Paul A.; Ozer, Huseyin TE; Erken, Eren; Ozturk, Mehmet A.; Yazici, Ayten; Cefle, Ayse; Onat, A. Mesut; Kisacik, Bunyamin; Pagnoux, Christian; Kasifoglu, Timucin; Seyahi, Emire; Fresko, Izzet; Seo, Philip; Sreih, Antoine; Warrington, Kenneth J.; Ytterberg, Steven R.; Cobankara, Veli; Cunninghame-Graham, Deborah S.; Vyse, Timothy J.; Pamuk, Omer N.; Tunc, Ercan; Dalkilic, Ediz; Bicakcigil, Muge; Yentur, Sibel P.; Wren, Jonathan D.; Merkel, Peter A.; Direskeneli, Haner; Sawalha, Amr H.

    2015-01-01

    Objective Takayasu’s arteritis is a rare large vessel vasculitis with incompletely understood etiology. We performed the first unbiased genome-wide association study (GWAS) in Takayasu’s arteritis. Methods Two independent Takayasu’s arteritis cohorts from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 European-derived patients and 1,047 controls. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu’s arteritis. Results We identified genetic susceptibility loci for Takayasu’s arteritis with a genome-wide level of significance in IL6 (rs2069837, OR= 2.07, P= 6.70×10−9), RPS9/LILRB3 (rs11666543, OR= 1.65, P= 2.34×10−8), and an intergenic locus on chromosome 21q22 (rs2836878, OR= 1.79, P= 3.62×10−10). The genetic susceptibility locus in RPS9/LILRB3 is located within the leukocyte receptor complex (LRC) gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P= 2.29×10−8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P <1×10−5) including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B in Takayasu’s arteritis. Conclusion This study identified novel genetic susceptibility loci for Takayasu’s arteritis and uncovered potentially important aspects in the pathophysiology of this form of vasculitis. PMID:25604533

  3. Exclusion of the dysplastic nevus syndrome (DNS) locus from the short arm of chromosome 1 by linkage studies in Dutch families.

    PubMed

    van Haeringen, A; Bergman, W; Nelen, M R; van der Kooij-Meijs, E; Hendrikse, I; Wijnen, J T; Khan, P M; Klasen, E C; Frants, R R

    1989-07-01

    Familial dysplastic nevus syndrome (DNS) is an autosomal dominant premalignant condition characterized by multiple large moles of variable size and color and a strongly increased risk for cutaneous malignant melanoma. In order to determine the chromosomal localization of the DNS gene, linkage studies were initiated in six large Dutch families. No support was obtained for linkage between the loci for DNS and the rhesus blood group on chromosome 1. Data from additional markers (DNF15S1, D1Z2, FUCA1, D1S17, D1S57, and PGM1) make it possible to exclude the DNS gene from the short arm of chromosome 1 in these Dutch families.

  4. Methylation at the PW71 locus on chromosome 15 in DNA derived from CVS and from amniocytes; implications for the use of the PW71 probe in prenatal diagnosis of the Prader-Willi and Angleman syndromes

    SciTech Connect

    Telleria, P.; Yu, C.C.; Brown, S.

    1994-09-01

    The probe PW71 spans a HpaII site in the Prader-Willi/Angleman Syndrome critical region on chromosome 15. A single Southern blot with this probe can be used to detect deletion and uniparental disomy. We attempted to determine the methylation state of the PW71 locus in DNA derived from prenatal sources. Southern blots of HindIII and HindIII/HpaII double digests of DNA from cultured amniocytes and CVS specimens were prepared and probed with the PW71 probe. The results from 6 cultured CVS specimens indicate that several HPAII sites recognized by the PW71 probe are not methylated in trophoblast. Four amniotic fluid cultures gave results which were not different from lymphocyte-derived DNA; however, in several cases, amniotic fluid cultures resulted in Southern blots identical to those from CVS. Since we did not have verified prenatal cases of chromosome 15 uniparental disomy, we were unable to determine whether the parent-of-origin specific methylation present in lymphocyte DNA is also present in amniocyte DNA. We conclude that prenatal determination of chromosome 15 uniparental disomy with this probe will be unreliable.

  5. Maternal uniparental disomy of chromosome 1 with reduction to homozygosity of the LAMB3 locus in a patient with Herlitz junctional epidermolysis bullosa.

    PubMed

    Pulkkinen, L; Bullrich, F; Czarnecki, P; Weiss, L; Uitto, J

    1997-09-01

    Junctional epidermolysis bullosa (JEB) is an autosomal recessive disorder characterized by blister formation at the level of the lamina lucida within the cutaneous basement-membrane zone. Classic lethal JEB (Herlitz type [H-JEB]; OMIM 226700) is frequently associated with premature-termination-codon mutations in both alleles of one of the three genes (LAMA3, LAMC2, or LAMB3) encoding the subunit polypeptides (alpha3, beta3, and gamma2) of laminin 5. In this study, we describe a unique patient with H-JEB, who was homozygous for a nonsense mutation, Q243X, in the LAMB3 gene on chromosome 1 and who had normal karyotype 46,XY. The mother was found to be a carrier of the Q243X mutation, whereas the father had two normal LAMB3 alleles. Nonpaternity was excluded by use of 11 microsatellite markers from six different chromosomes. The use of 17 partly or fully informative microsatellite markers spanning the entire chromosome 1 revealed that the patient had both maternal uniparental meroisodisomy of a 35-cM region on 1q containing the maternal LAMB3 mutation and maternal uniparental heterodisomy of other regions of chromosome 1. Thus, the results suggested that reduction to homozygosity of the 1q region containing the maternal LAMB3 mutation caused the H-JEB phenotype. The patient was normally developed at term and did not show overt dysmorphisms or malformations. This is the first description of uniparental disomy of human chromosome 1. PMID:9326326

  6. Three novel polymorphic microsatellite markers for the glaucoma locus GLC1B by datamining tetranucleotide repeats on chromosome 2p12-q12

    PubMed Central

    2009-01-01

    In order to identify new markers around the glaucoma locus GLC1B as a tool to refine its critical region at 2p11.2-2q11.2, we searched the critical region sequence obtained from the UCSC database for tetranucleotide (GATA)n and (GTCT)n repeats of at least 10 units in length. Three out of four potential microsatellite loci were found to be polymorphic, heterozygosity ranging from 64.56% to 79.59%. The identified markers are useful not only for GLC1B locus but also for the study of other disease loci at 2p11.2-2q11.2, a region with scarcity of microsatellite markers. PMID:21637444

  7. The analysis of a large Danish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 11q24.

    PubMed

    Rudkjøbing, Laura Aviaja; Eiberg, Hans; Mikkelsen, Hanne Birte; Binderup, Marie Louise Mølgaard; Bisgaard, Marie Luise

    2015-09-01

    Hereditary colorectal cancer accounts for approximately 30% of all colorectal cancers, but currently only 5% of these families can be explained by highly penetrant, inherited mutations. In the remaining 25% it is not possible to perform a gene test to identify the family members who would benefit from prophylactic screening. Consequently, all family members are asked to follow a screening program. The purpose of this study was to localize a new gene which causes colorectal cancer. We performed a linkage analysis using data from a SNP6.0 chip in one large family with 12 affected family members. We extended the linkage analysis with microsatellites (STS) and single nucleotide polymorphisms (SNP's) and looked for the loss of heterozygosity in tumour tissue. Furthermore, we performed the exome sequencing of one family member and we sequenced candidate genes by use of direct sequencing. Major rearrangements were excluded after karyotyping. The linkage analysis with SNP6 data revealed three candidate areas, on chromosome 2, 6 and 11 respectively, with a LOD score close to two and no negative LOD scores. After extended linkage analysis, the area on chromosome 6 was excluded, leaving areas on chromosome 2 and chromosome 11 with the highest possible LOD scores of 2.6. Two other studies have identified 11q24 as a candidate area for colorectal cancer susceptibility and this area is supported by our results. PMID:25724759

  8. Molecular analysis of a chromosome 4 inversion segregating in a large schizophrenia kindred from Hong Kong.

    PubMed

    Mensah, Albert K; De Luca, Vincenzo; Stachowiak, Beata; Noor, Abdul; Windpassinger, Christian; Lam, Stephen T S; Kennedy, James L; Scherer, Stephen W; Lo, Ivan F M; Vincent, John B

    2007-09-01

    The present study looks at a paracentric inversion on chromosome 4 [inv(4)(q13;q25)] in members of a large schizophrenia kindred from Hong Kong, and the possibility of a susceptibility gene for schizophrenia at one of the inversion breakpoints. Fluorescence in situ hybridization with BAC and fosmid clones was used to determine the location of the 4q13 and 4q25 breakpoints, however bioinformatic analysis indicated that no known genes are directly disrupted by the breakpoints. We identified several putative genes and expressed sequence tags (ESTs) from around the breakpoint regions, and have characterized them further in order to determine whether they may represent full-length mRNAs that are disrupted by the inversion. Overall, it appears that, while no known genes are disrupted, an as yet undiscovered gene, or indeed, a known gene, may be present near one of the breakpoints and may be disrupted by position effect. We hypothesized that either the 4q13 or 4q25 breakpoint region may contain a common susceptibility gene for schizophrenia. We genotyped 117 schizophrenia families for several short tandem repeat polymorphisms close to the breakpoints. Family based association testing showed no association at the 4q13 breakpoint region, but showed significant allelic association for marker D4S2989 at the 4q25 breakpoint region (p=0.016). This study suggests that the 4q breakpoint regions may harbour a gene that contributes to the illness in the large Hong Kong pedigree, and this 4q25 region should be examined further in other schizophrenia samples.

  9. A locus for the nystagmus-associated form of episodic ataxia maps to an 11-cM region on chromosome 19p

    SciTech Connect

    Kramer, P.L.; Gancher, S.T.; Nutt, J.G.

    1995-07-01

    Episodic ataxia (EA) is a rare neurological disorder characterized by attacks of generalized ataxia and near-normal neurological function between attacks. Most inherited cases are the result of an autosomal dominant condition with unknown neuropathology. It is heterogeneous and includes at least two distinct forms. In EA-1, attacks last minutes and interictal myokymia may be present. In EA-2, attacks may last hours and interictal nystagmus may occur. We reported linkage in four EA-1 families to chromosome 12p13 and identified mutations in these families in a potassium channel gene, KCNA1. Recently, we reported linkage in two EA-2 families to a 30-cM region on chromosome 19p. This report is based on members of the same two families and one additional kindred. 18 refs., 1 fig., 1 tab.

  10. Identification, genome mapping, and CTCF binding of potential insulators within the FXYD5-COX7A1 locus of human chromosome 19q13.12.

    PubMed

    Akopov, Sergey B; Ruda, Vera M; Batrak, Vera V; Vetchinova, Anna S; Chernov, Igor P; Nikolaev, Lev G; Bode, Jürgen; Sverdlov, Eugene D

    2006-10-01

    Identification of insulators is one of the most difficult problems in functional mapping of genomes. For this reason, up to now only a few insulators have been described. In this article we suggest an approach that allows direct isolation of insulators by a simple positive-negative selection based on blocking enhancer effects by insulators. The approach allows selection of fragments capable of blocking enhancers from mixtures of genomic fragments prepared from up to 1-Mb genomic regions. Using this approach, a 1-Mb human genome locus was analyzed and eight potential insulators were selected. Five of the eight sequences were positioned in intergenic regions and two were within introns. The genes of the alpha-polypeptide H+/K+ exchanging ATPase (ATP4A) and amyloid beta (A4) precursor-like protein 1 (APLP1) within the locus studied were found to be flanked by insulators on both sides. Both genes are characterized by distinct tissue-specific expression that differs from the tissue specificity of the surrounding genes. The data obtained are consistent with the conception that insulators subdivide genomic DNA into loop domains that comprise genes characterized by similar expression profiles. Using chromatin immunoprecipitation assay, we demonstrated also that at least six of the putative insulators revealed in this work could bind the CTCF transcription factor in vivo. We believe that the proposed approach could be a useful instrument for functional analysis of genomes.

  11. Identification, genome mapping, and CTCF binding of potential insulators within the FXYD5-COX7A1 locus of human chromosome 19q13.12.

    PubMed

    Akopov, Sergey B; Ruda, Vera M; Batrak, Vera V; Vetchinova, Anna S; Chernov, Igor P; Nikolaev, Lev G; Bode, Jürgen; Sverdlov, Eugene D

    2006-10-01

    Identification of insulators is one of the most difficult problems in functional mapping of genomes. For this reason, up to now only a few insulators have been described. In this article we suggest an approach that allows direct isolation of insulators by a simple positive-negative selection based on blocking enhancer effects by insulators. The approach allows selection of fragments capable of blocking enhancers from mixtures of genomic fragments prepared from up to 1-Mb genomic regions. Using this approach, a 1-Mb human genome locus was analyzed and eight potential insulators were selected. Five of the eight sequences were positioned in intergenic regions and two were within introns. The genes of the alpha-polypeptide H+/K+ exchanging ATPase (ATP4A) and amyloid beta (A4) precursor-like protein 1 (APLP1) within the locus studied were found to be flanked by insulators on both sides. Both genes are characterized by distinct tissue-specific expression that differs from the tissue specificity of the surrounding genes. The data obtained are consistent with the conception that insulators subdivide genomic DNA into loop domains that comprise genes characterized by similar expression profiles. Using chromatin immunoprecipitation assay, we demonstrated also that at least six of the putative insulators revealed in this work could bind the CTCF transcription factor in vivo. We believe that the proposed approach could be a useful instrument for functional analysis of genomes. PMID:17019650

  12. Genetics and Molecular Mapping of Black Rot Resistance Locus Xca1bc on Chromosome B-7 in Ethiopian Mustard (Brassica carinata A. Braun).

    PubMed

    Sharma, Brij Bihari; Kalia, Pritam; Yadava, Devendra Kumar; Singh, Dinesh; Sharma, Tilak Raj

    2016-01-01

    Black rot caused by Xanthomonas campestris pv. campestris (Pam.) Dowson is the most destructive disease of cauliflower causing huge loss to the farmers throughout the world. Since there are limited sources of resistance to black rot in B. oleracea (C genome Brassica), exploration of A and B genomes of Brassica was planned as these were thought to be potential reservoirs of black rot resistance gene(s). In our search for new gene(s) for black rot resistance, F2 mapping population was developed in Brassica carinata (BBCC) by crossing NPC-17, a susceptible genotype with NPC-9, a resistant genotype. Out of 364 Intron length polymorphic markers and microsatellite primers used in this study, 41 distinguished the parental lines. However, resistant and susceptible bulks could be distinguished by three markers At1g70610, SSR Na14-G02 and At1g71865 which were used for genotyping of F2 mapping population. These markers were placed along the resistance gene, according to order, covering a distance of 36.30 cM. Intron length polymorphic markers At1g70610 and At1g71865 were found to be linked to black rot resistance locus (Xca1bc) at 6.2 and 12.8 cM distance, respectively. This is the first report of identification of markers linked to Xca1bc locus in Brassica carinata on B-7 linkage group. Intron length polymorphic markers provided a novel and attractive option for marker assisted selection due to high cross transferability and cost effectiveness for marker assisted alien gene introgression into cauliflower. PMID:27023128

  13. Genetics and Molecular Mapping of Black Rot Resistance Locus Xca1bc on Chromosome B-7 in Ethiopian Mustard (Brassica carinata A. Braun)

    PubMed Central

    Sharma, Brij Bihari; Kalia, Pritam; Yadava, Devendra Kumar; Singh, Dinesh; Sharma, Tilak Raj

    2016-01-01

    Black rot caused by Xanthomonas campestris pv. campestris (Pam.) Dowson is the most destructive disease of cauliflower causing huge loss to the farmers throughout the world. Since there are limited sources of resistance to black rot in B. oleracea (C genome Brassica), exploration of A and B genomes of Brassica was planned as these were thought to be potential reservoirs of black rot resistance gene(s). In our search for new gene(s) for black rot resistance, F2 mapping population was developed in Brassica carinata (BBCC) by crossing NPC-17, a susceptible genotype with NPC-9, a resistant genotype. Out of 364 Intron length polymorphic markers and microsatellite primers used in this study, 41 distinguished the parental lines. However, resistant and susceptible bulks could be distinguished by three markers At1g70610, SSR Na14-G02 and At1g71865 which were used for genotyping of F2 mapping population. These markers were placed along the resistance gene, according to order, covering a distance of 36.30 cM. Intron length polymorphic markers At1g70610 and At1g71865 were found to be linked to black rot resistance locus (Xca1bc) at 6.2 and 12.8 cM distance, respectively. This is the first report of identification of markers linked to Xca1bc locus in Brassica carinata on B-7 linkage group. Intron length polymorphic markers provided a novel and attractive option for marker assisted selection due to high cross transferability and cost effectiveness for marker assisted alien gene introgression into cauliflower. PMID:27023128

  14. Genetics and Molecular Mapping of Black Rot Resistance Locus Xca1bc on Chromosome B-7 in Ethiopian Mustard (Brassica carinata A. Braun).

    PubMed

    Sharma, Brij Bihari; Kalia, Pritam; Yadava, Devendra Kumar; Singh, Dinesh; Sharma, Tilak Raj

    2016-01-01

    Black rot caused by Xanthomonas campestris pv. campestris (Pam.) Dowson is the most destructive disease of cauliflower causing huge loss to the farmers throughout the world. Since there are limited sources of resistance to black rot in B. oleracea (C genome Brassica), exploration of A and B genomes of Brassica was planned as these were thought to be potential reservoirs of black rot resistance gene(s). In our search for new gene(s) for black rot resistance, F2 mapping population was developed in Brassica carinata (BBCC) by crossing NPC-17, a susceptible genotype with NPC-9, a resistant genotype. Out of 364 Intron length polymorphic markers and microsatellite primers used in this study, 41 distinguished the parental lines. However, resistant and susceptible bulks could be distinguished by three markers At1g70610, SSR Na14-G02 and At1g71865 which were used for genotyping of F2 mapping population. These markers were placed along the resistance gene, according to order, covering a distance of 36.30 cM. Intron length polymorphic markers At1g70610 and At1g71865 were found to be linked to black rot resistance locus (Xca1bc) at 6.2 and 12.8 cM distance, respectively. This is the first report of identification of markers linked to Xca1bc locus in Brassica carinata on B-7 linkage group. Intron length polymorphic markers provided a novel and attractive option for marker assisted selection due to high cross transferability and cost effectiveness for marker assisted alien gene introgression into cauliflower.

  15. Construction and application of a bacterial artificial chromosome (BAC) library of Prunus armeniaca L. for the identification of clones linked to the self-incompatibility locus.

    PubMed

    Vilanova, S; Romero, C; Abernathy, D; Abbott, A G; Burgos, L; Llacer, G; Badenes, M L

    2003-08-01

    To facilitate gene discovery in the Rosaceae, a bacterial artificial chromosome (BAC) library was constructed using high-molecular-weight (HMW) DNA from apricot leaves (Prunus armeniaca L.). The library contains 101,376 clones (264, 384-well plates) with an average insert size of 64 kb, equivalent to 22-fold genome coverage. In the first application of this library, high-density filters were screened for self-incompatibility genes using apricot DNA probes. Eight positive BAC clones were detected and fingerprinted to determine clone relationships and assemble contigs. These results demonstrate the suitability of this library for gene identification and physical mapping of the apricot genome.

  16. 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.

  17. The Solanum pimpinellifolium Cf-ECP1 and Cf-ECP4 genes for resistance to Cladosporium fulvum are located at the Milky Way locus on the short arm of chromosome 1.

    PubMed

    Soumpourou, Eleni; Iakovidis, Michael; Chartrain, Laetitia; Lyall, Verity; Thomas, Colwyn M

    2007-11-01

    The interaction between tomato and the leaf mould pathogen Cladosporium fulvum is an excellent model to study gene-for-gene interactions and plant disease resistance gene evolution. Most Cf genes were introgressed into cultivated tomato (Solanum lycopersicum) from wild relatives such as S. pimpinellifolium and novel Cf-ECP genes were recently identified in this species. Our objective is to isolate Cf-ECP1, Cf-ECP2, Cf-ECP4 and Cf-ECP5 to increase our understanding of Cf gene evolution, and the molecular basis for recognition specificity in Cf proteins. The map locations of Cf-ECP2 and Cf-ECP5 have been reported previously and we report here that Cf-ECP1 and Cf-ECP4 map to a different locus on the short arm of chromosome 1. The analysis of selected recombinants and allelism tests showed both genes are located at Milky Way together with Cf-9 and Cf-4. Our results emphasise the importance of this locus in generating novel Cf genes for resistance to C. fulvum. Candidate genes for Cf-ECP1 and Cf-ECP4 were also identified by DNA gel blot analysis of bulked segregant pools. In addition, we generated functional cassettes for expression of the C. fulvum ECP1, ECP2, ECP4 and ECP5 proteins using recombinant Potato Virus X, and three ECPs were also expressed in stable transformed plants. Using marker-assisted selection we have also identified recombinants containing Cf-ECP1, Cf-ECP2, Cf-ECP4 or Cf-ECP5 in cis with a linked T-DNA carrying the non-autonomous Zea mays transposon Dissociation. Using these resources it should now be possible to isolate all four Cf-ECPs using transposon tagging, or a candidate gene strategy.

  18. Cytochrome oxidase subunit V gene of Neurospora crassa: DNA sequences, chromosomal mapping, and evidence that the cya-4 locus specifies the structural gene for subunit V.

    PubMed Central

    Sachs, M S; Bertrand, H; Metzenberg, R L; RajBhandary, U L

    1989-01-01

    The sequences of cDNA and genomic DNA clones for Neurospora cytochrome oxidase subunit V show that the protein is synthesized as a 171-amino-acid precursor containing a 27-amino-acid N-terminal extension. The subunit V protein sequence is 34% identical to that of Saccharomyces cerevisiae subunit V; these proteins, as well as the corresponding bovine subunit, subunit IV, contain a single hydrophobic domain which most likely spans the inner mitochondrial membrane. The Neurospora crassa subunit V gene (cox5) contains two introns, 398 and 68 nucleotides long, which share the conserved intron boundaries 5'GTRNGT...CAG3' and the internal consensus sequence ACTRACA. Two short sequences, YGCCAG and YCCGTTY, are repeated four times each in the cox5 gene upstream of the mRNA 5' termini. The cox5 mRNA 5' ends are heterogeneous, with the major mRNA 5' end located 144 to 147 nucleotides upstream from the translational start site. The mRNA contains a 3'-untranslated region of 186 to 187 nucleotides. Using restriction-fragment-length polymorphism, we mapped the cox5 gene to linkage group IIR, close to the arg-5 locus. Since one of the mutations causing cytochrome oxidase deficiency in N. crassa, cya-4-23, also maps there, we transformed the cya-4-23 strain with the wild-type cox5 gene. In contrast to cya-4-23 cells, which grow slowly, cox5 transformants grew quickly, contained cytochrome oxidase, and had 8- to 11-fold-higher levels of subunit V in their mitochondria. These data suggest (i) that the cya-4 locus in N. crassa specifies structural information for cytochrome oxidase subunit V and (ii) that, in N. crassa, as in S. cerevisiae, deficiencies in the production of nuclearly encoded cytochrome oxidase subunits result in deficiency in cytochrome oxidase activity. Finally, we show that the lower levels of subunit V in cya-4-23 cells are most likely due to substantially reduced levels of translatable subunit V mRNA. Images PMID:2540423

  19. Combined Analysis of Genome Scans of Dutch and Finnish Families Reveals a Susceptibility Locus for High-Density Lipoprotein Cholesterol on Chromosome 16q

    PubMed Central

    Pajukanta, Päivi; Allayee, Hooman; Krass, Kelly L.; Kuraishy, Ali; Soro, Aino; Lilja, Heidi E.; Mar, Rebecca; Taskinen, Marja-Riitta; Nuotio, Ilpo; Laakso, Markku; Rotter, Jerome I.; de Bruin, Tjerk W. A.; Cantor, Rita M.; Lusis, Aldons J.; Peltonen, Leena

    2003-01-01

    Several genomewide screens have been performed to identify novel loci predisposing to unfavorable serum lipid levels and coronary heart disease (CHD). We hypothesized that the accumulating data of these screens in different study populations could be combined to verify which of the identified loci truly harbor susceptibility genes. The power of this strategy has recently been demonstrated with other complex diseases, such as inflammatory bowel disease and asthma. We assessed the largely unknown genetic background of CHD by investigating the most common dyslipidemia predisposing to CHD, familial combined hyperlipidemia (FCHL), affecting 1%–2% of Western populations and 10%–20% of families with premature CHD. To be able to perform a combined data analysis, we unified the diagnostic criteria for FCHL and its component traits and combined the data from two genomewide scans performed in two populations, the Finns and the Dutch. As a result of our pooled data analysis, we identified three chromosomal regions, on chromosomes 2p25.1, 9p23, and 16q24.1, exceeding the statistical significance level of a LOD score >2.0. The 2p25.1 region was detected for the FCHL trait, and the 9p23 and 16q24.1 regions were detected for the low high-density lipoprotein cholesterol (HDL-C) trait. In addition, the previously recognized 1q21 region also obtained additional support in the other study sample, when the triglyceride trait was used. Analysis of the 16q24.1 region resulted in a statistically significant LOD score of 3.6 when the data from Finnish families with low HDL-C were included in the analysis. To search for the underlying gene in the 16q24.1 region, we investigated a novel functional and positional candidate gene, helix/forkhead transcription factor (FOXC2), by sequencing and by genotyping of two single-nucleotide polymorphisms in the families. PMID:12638083

  20. Mapping of a macular drusen susceptibility locus in rhesus macaques to the homologue of human chromosome 6q14-15.

    PubMed

    Singh, Krishna K; Ristau, Steven; Dawson, William W; Krawczak, Michael; Schmidtke, Jörg

    2005-10-01

    Rhesus macaques (Macaca mulatta) are a natural model for retinal drusen formation. The present study aimed at clarifying whether chromosomal regions homologous to candidate genes for drusen formation and progression in humans are also associated with a drusen phenotype in rhesus macaques. Some 42 genetic markers from seven chromosomal regions implicated in macular degeneration syndromes in humans were tested for whether they identified homologous, polymorphic sequences in rhesus DNA. This was found to be the case for seven markers, all of which were subsequently screened for the presence of potentially disease-predisposing alleles in 52 randomly chosen adult animals from the Cayo Santiago population of rhesus macaques (Caribbean Primate Research Center, PR, USA). The high drusen prevalence expected in the Cayo Santiago colony was confirmed in our sample in that 38 animals were found to have drusen (73%). Logistic regression analysis revealed that some alleles of the rhesus homologue of anonymous human marker D6S1036 were consistently over-represented among affected animals. Of two candidate genes located in the respective region, allelic variation in one (IMPG1) showed strong association with drusen formation. We conclude that one or more genes located at the rhesus homologue of human 6q14-15 are likely to play a role in retinal drusen formation, a finding that represents a first step towards the identification of genetic factors implicated in macular drusen formation in rhesus macaques. This is an important tool for the separation of genetic and environmental factors which must occur before satisfactory management methods can be developed.

  1. Recombinational and physical mapping of the locus for primary open-angle glaucoma (GLC1A) on chromosome 1q23-q25

    SciTech Connect

    Belmouden, A.; Adam, M.F.; De Dinechin, S.D. |

    1997-02-01

    Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in industrialized countries. A locus for juvenile-onset POAG, GLC1A, has been mapped to 1q21-q31 in a 9-cM interval. With recombinant haplotypes, we have now reduced the GLC1A interval to a maximum of 3 cM, between the D1S452/NGA1/D1S210 and NGA5 loci. These loci are 2.8 Mb apart on a 4.7-Mb contig that we have completed between the D1S2851 and D1S218 loci and that includes 96 YAC clones and 48 STSs. The new GLC1A interval itself is now covered by 25 YACs, 30 STSs, and 16 restriction enzyme site landmarks. The lack of a NotI site suggests that the region has few CpG islands and a low gene content. This is compatible with its predominant cytogenetic location on the 1q24 G-band. Finally, we have excluded important candidate genes, including genes coding for three ATPases (AMB1, ATP2B4, ATPlA2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify the GLC1A gene. 59 refs., 3 figs., 3 tabs.

  2. Implication of a chromosome 15q15.2 locus in regulating UBR1 and predisposing smokers to MGMT methylation in lung

    PubMed Central

    Leng, Shuguang; Wu, Guodong; Collins, Leonard B.; Thomas, Cynthia L.; Tellez, Carmen S.; Jauregui, Andrew R.; Picchi, Maria A.; Zhang, Xiequn; Juri, Daniel E.; Desai, Dhimant; Amin, Shantu G.; Crowell, Richard E.; Stidley, Christine A.; Liu, Yushi; Swenberg, James A.; Lin, Yong; Wathelet, Marc G.; Gilliland, Frank D.; Belinsky, Steven A.

    2015-01-01

    O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that protects cells from carcinogenic effects of alkylating agents; however, MGMT is silenced by promoter hypermethylation during carcinogenesis. A single nucleotide polymorphism (SNP) in an enhancer in the MGMT promoter was previously identified to be highly significantly associated with risk for MGMT methylation in lung cancer and sputum from smokers. To further genetic investigations, a genome-wide association and replication study was conducted in two smoker cohorts to identify novel loci for MGMT methylation in sputum that were independent of the MGMT enhancer polymorphism. Two novel trans-acting loci (15q15.2 and 17q24.3) that were identified acted together with the enhancer SNP to empower risk prediction for MGMT methylation. We found that the predisposition to MGMT methylation arising from the 15q15.2 locus involved regulation of the ubiquitin protein ligase E3 component UBR1. UBR1 attenuation reduced turnover of MGMT protein and increased repair of O6-methylguanine in nitrosomethylurea-treated human bronchial epithelial cells (HBEC), while also reducing MGMT promoter activity and abolishing MGMT induction. Overall, our results substantiate reduced gene transcription as a major mechanism for predisposition to MGMT methylation in the lungs of smokers, and support the importance of UBR1 in regulating MGMT homeostasis and DNA repair of alkylated DNA adducts in cells. PMID:26183928

  3. Original Research: Generation of non-deletional hereditary persistence of fetal hemoglobin β-globin locus yeast artificial chromosome transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH

    PubMed Central

    Braghini, Carolina A; Costa, Flavia C; Fedosyuk, Halyna; Neades, Renee Y; Novikova, Lesya V; Parker, Matthew P; Winefield, Robert D

    2016-01-01

    Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain β-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of γ-globin in adulthood, show reduced disease pathophysiology. Hereditary persistence of fetal hemoglobin is caused by β-globin locus deletions (deletional hereditary persistence of fetal hemoglobin) or γ-globin gene promoter point mutations (non-deletional hereditary persistence of fetal hemoglobin). Current research has focused on elucidating the pathways involved in the maintenance/reactivation of γ-globin in adult life. To better understand these pathways, we generated new β-globin locus yeast artificial chromosome transgenic mice bearing the Aγ-globin -175 T > C or -195 C > G hereditary persistence of fetal hemoglobin mutations to model naturally occurring hereditary persistence of fetal hemoglobin. Adult -175 and -195 mutant β-YAC mice displayed a hereditary persistence of fetal hemoglobin phenotype, as measured at the mRNA and protein levels. The molecular basis for these phenotypes was examined by chromatin immunoprecipitation of transcription factor/co-factor binding, including YY1, PAX1, TAL1, LMO2, and LDB1. In -175 HPFH versus wild-type samples, the occupancy of LMO2, TAL1 and LDB1 proteins was enriched in HPFH mice (5.8-fold, 5.2-fold and 2.7-fold, respectively), a result that concurs with a recent study in cell lines showing that these proteins form a complex with GATA-1 to mediate long-range interactions between the locus control region and the Aγ-globin gene. Both hereditary persistence of fetal hemoglobin mutations result in a gain of Aγ-globin activation, in contrast to other hereditary persistence of fetal hemoglobin mutations that result in a loss of repression. The mice provide additional tools to study

  4. A Non-Coding RNA Within the Rasgrf1 Locus in Mouse Is Imprinted and Regulated by Its Homologous Chromosome in Trans

    PubMed Central

    Holmes, Rebecca; Soloway, Paul D.

    2010-01-01

    Background Rasgrf1 is imprinted in mouse, displaying paternal allele specific expression in neonatal brain. Paternal expression is accompanied by paternal-specific DNA methylation at a differentially methylated domain (DMD) within the locus. The cis-acting elements necessary for Rasgrf1 imprinting are known. A series of tandem DNA repeats control methylation of the adjacent DMD, which is a methylation sensitive enhancer-blocking element. These two sequences constitute a binary switch that controls imprinting and represents the Imprinting Control Region (ICR). One paternally transmitted mutation, which helped define the ICR, induced paramutation, in trans, on the maternal allele. Like many imprinted genes, Rasgrf1 lies within an imprinted cluster. One of four noncoding transcripts in the cluster, AK015891, is known to be imprinted. Methodology/Principal Findings Here we demonstrate that an additional noncoding RNA, AK029869, is imprinted and paternally expressed in brain throughout development. Intriguingly, any of several maternally inherited ICR mutations affected expression of the paternal AK029869 transcript in trans. Furthermore, we found that the ICR mutations exert different trans effects on AK029869 at different developmental times. Conclusions/Significance Few trans effects have been defined in mammals and, those that exist, do not show the great variation seen at the Rasgrf1 imprinted domain, either in terms of the large number of mutations that produce the effects or the range of phenotypes that emerge when they are seen. These results suggest that trans regulation of gene expression may be more common than originally appreciated and that where trans regulation occurs it can change dynamically during development. PMID:21072176

  5. Qualitative analysis of mouse specific-locus mutations: information on genetic organization, gene expression, and the chromosomal nature of induced lesions

    SciTech Connect

    Russell, L.B.

    1982-01-01

    Analysis of mouse specific-locus (SL) mutations at three loci has identified over 33 distinct complementation groups - most of which are probably overlapping deficiencies - and 13 to 14 new functional units. The complementation maps that have been generated for the d-se and c regions include numerous vital functions; however, some of the genes in these regions are non-vital. At such loci, hypomorphic mutants must represent intragenic alterations, and some viable nulls could conceivably be intragenic lesions also. Analysis of SL mutations has provided information on genetic expression. Homozygous deficiencies can be completely viable or can kill at any one of a range of developmental stages. Heterozygonus deficiencies of up to 6 cM or more in genetic length have been recovered and propagated. The time of death of homozygous and the degree of inviability of heterozygous deficiencies are related more to specific content of the missing segment than to its length. Combinations of deficiencies with x-autosome translocations that inactivate the homologous region in a mosaic fashion have shown that organismic lethals are not necessarily cell lethal. The spectrum of mutations induced depends on the nature of the mutagen and the type of germ cell exposed. Radiation of spermatogonia produces intragenic as well as null mutations. Spontaneous mutations have an admixture of types not present in populations of mutations induced in germ cells, and this raises doubts concerning the accuracy of doubling-dose calculations in genetic risk estimation. The analysis of SL mutations has yielded genetic tools for the construction of detailed gene-dosage series, cis-trans comparisons, the mapping of known genes and identification of new genes, genetic rescue of various types, and the identification and isolation of DNA sequences. (ERB)

  6. A genome-wide association study reveals a quantitative trait locus for days open on chromosome 2 in Japanese Black cattle.

    PubMed

    Sasaki, Shinji; Ibi, Takayuki; Kojima, Takatoshi; Sugimoto, Yoshikazu

    2016-02-01

    Days open (DO), which is the interval from calving to conception, is an important trait related to reproductive performance in cattle. To identify quantitative trait loci for DO in Japanese Black cattle, we conducted a genome-wide association study with 33,303 single nucleotide polymorphisms (SNPs) using 459 animals with extreme DO values selected from a larger group of 15,488 animals. We identified a SNP on bovine chromosome 2 (BTA2) that was associated with DO. After imputation using phased haplotype data inferred from 586 812 SNPs of 1041 Japanese Black cattle, six SNPs associated with DO were located in an 8.5-kb region of high linkage disequilibrium on BTA2. These SNPs were located on the telomeric side at a distance of 177 kb from the parathyroid hormone 2 receptor (PTH2R) gene. The association was replicated in a sample of 1778 animals. In the replicated population, the frequency of the reduced-DO allele (Q) was 0.63, and it accounted for 1.72% of the total genetic variance. The effect of a Q-to-q allele substitution on DO was a decrease of 3.74 days. The results suggest that the Q allele could serve as a marker in Japanese Black cattle to select animals with superior DO performance.

  7. In situ localization of the genetic locus encoding the lysosomal acid lipase/cholesteryl esterase (LIPA) deficient in wolman disease to chromosome 10q23. 2-q23. 3

    SciTech Connect

    Anderson, R.A.; Rao, N.; Byrum, R.S.; Rothschild, C.B.; Bowden, D.W.; Hayworth, R.; Pettenati, M. )

    1993-01-01

    Human acid lipase/cholesteryl esterase (EC 3.1.1.13) is a 46-kDa glycoprotein required for the lysosomal hydrolysis of cholesteryl esters and triglycerides that cells acquire through the receptor-mediated endocytosis of low-density lipoproteins. This activity is essential in the provision of free cholesterol for cell metabolism as well as for the feedback signal that modulates endogenous cellular cholesterol production. The extremely low level of lysosomal acid lipase in patients afflicted with the hereditary, allelic lysosomal storage disorders Woman disease (WD) and cholesteryl ester storage disease (CESD) (MIM Number 278000 (6)) is associated with the massive intralysosomal lipid storage and derangements in the regulation of cellular cholesterol production (10). Both WD and CESD cells lack a specific acid lipase isoenzyme and it is thought that the different mutations associated with WD and CESD are in the structural gene for this isoenzyme, LIPA. Analysis of the activity of the acid lipase isoenzyme in cell extracts from human-Chinese hamster somatic cell hybrids (4, 11) demonstrated the concordant segregation of the gene locus for lysosomal acid lipase with the glutamate oxaloacetate transaminase-1 (GOT1) enzyme marker for human chromosome 10 which was subsequently localized to 10q24.1 q25.1 (8). 11 refs., 1 figs.

  8. Targeted introduction of a diphtheria toxin resistant mutation into the chromosomal EF-2 locus of Pichia pastoris and expression of immunotoxin in the EF-2 mutants.

    PubMed

    Liu, Yuan Yi; Woo, Jung Hee; Neville, David M

    2003-08-01

    In an attempt to increase the production of a diphtheria toxin (DT) based immunotoxin by Pichia pastoris, we have created DT-resistant mutants that contain a substitution of arginine for glycine at position 701 in elongation factor 2 (EF-2). To achieve this, we first cloned and characterized the EF-2 gene (PEF1), and then made a construct pBLURA-Delta5'mutEF-2 that efficiently introduces specific mutations into the chromosomal EF-2 gene in P. pastoris by in vivo homologous recombination. pBLURA-Delta5(')mutEF-2 contains a selection marker URA3 and a 5' truncated form of the P. pastoris PEF1 that had been modified in vitro to carry the nucleotide mutations for the Gly(701) to Arg transition. Unlike the non-mutated strains, the EF-2 mutants are resistant to high-level intracellular expression of DT A chain that can catalyze the ADP-ribosylation. When used to express the secreted bivalent anti-T cell immunotoxin, A-dmDT390-bisFv(G4S), the EF-2 mutant strains showed increased viability compared to the non-mutated strains. However, they did not show an advantage over the non-mutated expressing strain in the production of the immunotoxin. Western blotting analysis revealed that although the EF-2 mutants did not increase the accumulation of intact A-dmDT390-bisFv(G4S) in the culture medium, they generated larger amounts of degraded products found in both the medium and cell pellets compared to the non-mutant expressing clone. In addition, double copy expression resulted in greater amounts of intact immunotoxin being retained within cellular compartments as well as degraded products. Based on these findings, we suggest that the secretory capacity may be rate limiting for divalent immunotoxin production in P. pastoris. PMID:12880776

  9. Two mutations in the locus control region hypersensitivity site-2 (5' HS-2) of haplotype 19 beta s chromosomes alter binding of trans-acting factors.

    PubMed

    Morgan, J C; Scott, D F; Lanclos, K D

    1996-01-01

    There are five major haplotypes associated with sickle cell anemia (SS). Individuals homozygous for haplotypes 3 (Senegal) and 31 (Saudi Arabian) have high fetal hemoglobin (HbF) levels (15 to 30% of total hemoglobin) whereas individuals homozygous for haplotypes 17 (Cameroon), 19 (Benin), and 20 (Bantu) have low HbF levels (1 to 10%). We previously identified several point mutations in the LCR 5'HS-2 that were specific for haplotype 19 beta s chromosomes (compared to the GenBank HUMHBB reference sequence, T-->G at position 8580, A-->G at position 8598, and A-->T at position 9114). We postulated that one or more of these mutations may alter the binding of specific trans-acting factors and ultimately affect the expression of HbF in these sickle cell patients. We performed gel mobility shift assays using 32P-end-labeled double-stranded 19mers corresponding to each of the LCR 5'HS-2 normal (GenBank) and mutant sequences. Nuclear extracts prepared from HeLa and HEL cells were used in our experiments and neither the normal nor mutant sequence at position 8580 bound trans-acting factors in either nuclear extract. The 8598 mutant increased binding of Sp1; using purified protein and both nuclear extracts. HEL extracts were used to quantify the increase in Sp1 binding to the 8598 mutation and we found an increase in binding of 66 and 47%, respectively, in two shifted bands. The 9114 mutation sharply decreased binding of an unknown trans-acting factor by 74%. This factor was present in both HeLa and HEL nuclear extracts.

  10. Chromosomal Locus for Cadmium Resistance in Pseudomonas putida Consisting of a Cadmium-Transporting ATPase and a MerR Family Response Regulator

    PubMed Central

    Lee, Seon-Woo; Glickmann, Eric; Cooksey, Donald A.

    2001-01-01

    Pseudomonads from environmental sources vary widely in their sensitivity to cadmium, but the basis for this resistance is largely uncharactarized. A chromosomal fragment encoding cadmium resistance was cloned from Pseudomonas putida 06909, a rhizosphere bacterium, and sequence analysis revealed two divergently transcribed genes, cadA and cadR. CadA was similar to cadmium-transporting ATPases known mostly from gram-positive bacteria, and to ZntA, a lead-, zinc-, and cadmium-transporting ATPase from Escherichia coli. CadR was related to the MerR family of response regulators that normally control mercury detoxification in other bacterial systems. A related gene, zntR, regulates zntA in E. coli, but it is not contiguous with zntA in the E. coli genome as cadA and cadR were in P. putida. In addition, unlike ZntA and other CadA homologs, but similar to the predicted product of gene PA3690 in the P. aeruginosa genome, the P. putida CadA sequence had a histidine-rich N-terminal extension. CadR and the product of PA3689 of P. aeruginosa also had histidine-rich C-terminal extensions not found in other MerR family response regulators. Mutational analysis indicated that cadA and cadR are fully responsible for cadmium resistance and partially for zinc resistance. However, unlike zntA, they did not confer significant levels of lead resistance. The cadA promoter was responsive to Cd(II), Pb(II), and Zn(II), while the cadR promoter was only induced by Cd(II). CadR apparently represses its own expression at the transcriptional level. However, CadR apparently does not repress cadA. Homologs of the cadmium-transporting ATPase were detected in many other Pseudomonas species. PMID:11282588

  11. A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: a preliminary study.

    PubMed

    Baron-Cohen, Simon; Murphy, Laura; Chakrabarti, Bhismadev; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Warrier, Varun

    2014-01-01

    Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419) versus low (n = 183) mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p<1.5×10(-5), 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 ×10(-6)). In this analysis, one of the SNPs (rs789859) showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115) were nominally significant (lowest p-value 3.278 × 10(-4)). Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64). The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study.

  12. High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass.

    PubMed

    Nie, Ying; Kumarasamy, Sivarajan; Waghulde, Harshal; Cheng, Xi; Mell, Blair; Czernik, Piotr J; Lecka-Czernik, Beata; Joe, Bina

    2016-06-01

    Through linkage analysis of the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), a blood pressure (BP) quantitative trait locus (QTL) was previously located on rat chromosome 9. Subsequent substitution mapping studies of this QTL revealed multiple BP QTLs within the originally identified logarithm of odds plot by linkage analysis. The focus of this study was on a 14.39 Mb region, the distal portion of which remained unmapped in our previous studies. High-resolution substitution mapping for a BP QTL in the setting of a high-salt diet indicated that an SHR-derived congenic segment of 787.9 kb containing the gene secreted phosphoprotein-2 (Spp2) lowered BP and urinary protein excretion. A nonsynonymous G/T polymorphism in the Spp2 gene was detected between the S and S.SHR congenic rats. A survey of 45 strains showed that the T allele was rare, being detected only in some substrains of SHR and WKY. Protein modeling prediction through SWISSPROT indicated that the predicted protein product of this variant was significantly altered. Importantly, in addition to improved cardiovascular and renal function, high salt-fed congenic animals carrying the SHR T variant of Spp2 had significantly lower bone mass and altered bone microarchitecture. Total bone volume and volume of trabecular bone, cortical thickness, and degree of mineralization of cortical bone were all significantly reduced in congenic rats. Our study points to opposing effects of a congenic segment containing the prioritized candidate gene Spp2 on BP and bone mass. PMID:27113531

  13. A new type of genetic regulation of allogeneic response. A novel locus on mouse chromosome 4, Alan2 controls MLC reactivity to three different alloantigens: C57BL/10, BALB/c and CBA.

    PubMed

    Havelková, H; Badalová, J; Demant, P; Lipoldová, M

    2000-12-01

    The intensity of the mixed lymphocyte response (MLR) depends on the genetic disparity between the donors of responding and stimulating cells. Differences in the major histocompatibility complex (MHC) and Mls1 antigens induce the strongest responses. However, even with comparable incompatibilities in MHC and Mls antigens, some strains of genetically defined mice respond remarkably better than other strains. Apparently other, so far undefined, genetic factors contribute to the magnitude of the MLR. The strain OcB-9 (H2pz) has 87.5% genes from the strain O20/A (O20) and 12.5% genes from strain B10.O20 (both H2pz). In spite of the overal similarity of their genomes, OcB-9 mice differed from O20 mice in response to three different alloantigens C57BL/10 (H2b), BALB/c (H2d) and CBA (H2k). As both O20 and OcB-9 strains carry identical haplotype H2pz, their differences in alloantigen response depend only on non-MHC genes. We analyzed the genetic basis of these strain differences using (OcB-9 x O20)F2 hybrids, and we mapped a novel locus Alan2 (Alloantigen response 2) on chromosome 4 near D4Mit72 that influences the response to all alloantigens tested. This linkage was significant for C57BL/10 and for BALB/c alloantigens (corrected P values 0.0475 and 0.0158, respectively) and highly suggestive for CBA (corrected P = 0.0661). The response to DBA/1 (H2q) alloantigens exhibited a similar pattern but the linkage was not significant. As MLR reflects the recognition phase of transplantation reaction, identification of human counterparts of the Alan genes and a better understanding of the regulation of alloresponsiveness might lead to a better prediction of patients' reactions to allografts and to a more individualized measures to prevent rejection.

  14. Degeneration of a Nonrecombining Chromosome

    NASA Astrophysics Data System (ADS)

    Rice, William R.

    1994-01-01

    Comparative studies suggest that sex chromosomes begin as ordinary autosomes that happen to carry a major sex determining locus. Over evolutionary time the Y chromosome is selected to stop recombining with the X chromosome, perhaps in response to accumulation of alleles beneficial to the heterogametic but harmful to the homogametic sex. Population genetic theory predicts that a nonrecombining Y chromosome should degenerate. Here this prediction is tested by application of specific selection pressures to Drosophila melanogaster populations. Results demonstrate the decay of a nonrecombining, nascent Y chromosome and the capacity for recombination to ameliorate such decay.

  15. Functional complementation of ataxia-telangiectasia group D (AT-D) cells by microcell-mediated chromosome transfer and mapping of the AT-D locus to the region 11q22-23

    SciTech Connect

    Lambert, C.; Donlon, T.; Friedberg, E.C. ); Schultz, R.A.; McDaniel, L.D. ); Smith, M.; Wagner-McPherson, C.; Stanbridge, E.J. )

    1991-07-01

    The hereditary human disease ataxia-telangiectasia (AT) is characterized by phenotypic complexity at the cellular level. The authors show that multiple mutant phenotypes of immortalized AT cells from genetic complementation group D (AT-D) are corrected after the introduction of a single human chromosome from a human-mouse hybrid line by microcell-mediated chromosome transfer. This chromosome is cytogenetically abnormal. It consists primarily of human chromosome 18, but it carries translocated material from the region 11q22-23, where one or more AT genes have been previously mapped by linkage analysis. A cytogenetically normal human chromosome 18 does not complement AT-D cells after microcell-mediated transfer, whereas a normal human chromosome 11 does. They conclude that the AT-D gene is located on chromosome 11q22-23.

  16. Locus heterogeneity in autosomal dominant spinocerebellar ataxia: Evidence for the existence of a fifth locus

    SciTech Connect

    Sarrazin, J.; Rouleau, G.A.; Andermann, E.

    1994-09-01

    The autosomal dominantly inherited spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders. To date, four loci have been identified: the SCA-1 locus (on chromosome (chr) 6p), the SCA-2 locus (on chr 12q), the SCA-3/MJD locus (on chr 14q), and more recently an SCA-4 locus was described (chr 16q) in a Utah kindred. We have studied one large French Canadian kindred with four generations of living affected individuals segregating an autosomal dominant form of SCA. Linkage analysis using anonymous DNA markers which flank the four previously described loci significantly excludes the French Canadian kindred from the SCA-1, SCA-2, SCA-3/MJD and SCA-4 loci. Therefore a fifth, still unmapped, SCA locus remains to be identified.

  17. Analysis of 55 autoimmune disease and type II diabetes loci: further confirmation of chromosomes 4q27, 12q13.2 and 12q24.13 as type I diabetes loci, and support for a new locus, 12q13.3-q14.1.

    PubMed

    Cooper, J D; Walker, N M; Healy, B C; Smyth, D J; Downes, K; Todd, J A

    2009-12-01

    A candidate gene study was conducted on 10 established type II diabetes genes and 45 genes associated with autoimmune diseases, including type I diabetes (T1D), in a maximum of 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. Associations at P values <10(-3) were found for three known T1D regions at chromosomes 4q27, 12q13.2 and 12q24.13 (http://www.T1DBase.org). Support was obtained for a newly identified T1D candidate locus on chromosome 12q13.3-12q14.1 (rs1678536/KIF5A: P=8.1 x 10(-3); relative risk (RR) for minor allele=0.89, 95% CI=0.82-0.97), which has a separate association from the previously reported T1D candidate locus ERBB3/12q13.2-q13.3. Our new evidence adds to that previously published for the same gene region in a T1D case-control study (rs1678542; P=3.0 x 10(-4); odds ratio (OR)=0.92, 95% CI=0.88-0.96). This region, which contains many genes, has also been associated with rheumatoid arthritis. PMID:19956108

  18. Recombinant Inbred Strain and Interspecific Backcross Analysis of Molecular Markers Flanking the Murine Agouti Coat Color Locus

    PubMed Central

    Siracusa, L. D.; Buchberg, A. M.; Copeland, N. G.; Jenkins, N. A.

    1989-01-01

    Recombinant inbred strain and interspecific backcross mice were used to create a molecular genetic linkage map of the distal portion of mouse chromosome 2. The orientation and distance of the Ada, Emv-13, Emv-15, Hck-1, Il-1a, Pck-1, Psp, Src-1 and Svp-1 loci from the β(2)-microglobulin locus and the agouti locus were established. Our mapping results have provided the identification of molecular markers both proximal and distal to the agouti locus. The recombinants obtained provide valuable resources for determining the direction of chromosome walking experiments designed to clone sequences at the agouti locus. Comparisons between the mouse and human genome maps suggest that the human homolog of the agouti locus resides on human chromosome 20q. Three loci not present on mouse chromosome 2 were also identified and were provisionally named Psp-2, Hck-2 and Hck-3. The Psp-2 locus maps to mouse chromosome 14. The Hck-2 locus maps near the centromere of mouse chromosome 4 and may identify the Lyn locus. The Hck-3 locus maps near the distal end of mouse chromosome 4 and may identify the Lck locus. PMID:2759422

  19. Loss of a 1.6 Mb chromosome in Pyricularia oryzae harboring two alleles of AvrPik leads to acquisition of virulence to rice cultivars containing resistance alleles at the Pik locus.

    PubMed

    Kusaba, Motoaki; Mochida, Taiga; Naridomi, Takeshi; Fujita, Yoshikatsu; Chuma, Izumi; Tosa, Yukio

    2014-11-01

    A small and extra chromosome of 1.6 Mb was previously identified in a Pyricularia oryzae strain, 84R-62B. To understand a role of the 1.6 Mb chromosome in the pathogenic changeability of P. oryzae, we performed experiments designed to characterize the 1.6 Mb chromosome in the present study. A gene family encoding secreted protein Pex31s in P. oryzae consists of five homologs, Pex31-A to -E. Among them, Pex31-A and -D are known to be recognized by Pik-m and Pik/Pik-m/Pik-p, respectively. In the present study, we identified Pex31-A and -D in the genome of 84R-62B. Segregation analyses using an F1 population between 84R-62B and another rice blast strain, Y93-245c-2, revealed a strong linkage between the two homologs and the 1.6 Mb chromosome of 84R-62B. A CHEF-Southern analysis revealed an association between the 1.6 Mb chromosome and the homologs, indicating that both homologs are located on the 1.6 Mb chromosome of 84R-62B. The loss of the 1.6 Mb chromosome was observed in subcultures of a F1 progeny, F1-327. These subcultures concomitantly acquired virulence on Pik, Pik-m, and Pik-p. The present study is the first report showing that loss of a small and extra chromosome leads to pathogenic mutation of P. oryzae and may provide a new insight into the mechanisms generating pathogenic variation of this fungus. PMID:25056242

  20. Combination of null alleles with 7+9 allelic pair at Glu-B1 locus on the long arm of group 1 chromosome improves wheat dough functionality for tortillas

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deletion of one or more high molecular weight glutenin subunit (HMW-GS) alleles reduces gluten strength in a way that may be beneficial for tortilla quality. Wheat lines in which one or more of the HMW-GS alleles were absent from Glu-A1, Glu-B1 or Glu-D1 locus (deletion lines) were compared with non...

  1. 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.

  2. 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 ...

  3. A suppressor locus for MODY3-diabetes

    PubMed Central

    Garcia-Gonzalez, Miguel A.; Carette, Claire; Bagattin, Alessia; Chiral, Magali; Makinistoglu, Munevver Parla; Garbay, Serge; Prévost, Géraldine; Madaras, Cécile; Hérault, Yann; Leibovici, Michel; Pontoglio, Marco

    2016-01-01

    Maturity Onset Diabetes of the Young type 3 (MODY3), linked to mutations in the transcription factor HNF1A, is the most prevalent form of monogenic diabetes mellitus. HNF1alpha-deficiency leads to defective insulin secretion via a molecular mechanism that is still not completely understood. Moreover, in MODY3 patients the severity of insulin secretion can be extremely variable even in the same kindred, indicating that modifier genes may control the onset of the disease. With the use of a mouse model for HNF1alpha-deficiency, we show here that specific genetic backgrounds (C3H and CBA) carry a powerful genetic suppressor of diabetes. A genome scan analysis led to the identification of a major suppressor locus on chromosome 3 (Moda1). Moda1 locus contains 11 genes with non-synonymous SNPs that significantly interacts with other loci on chromosomes 4, 11 and 18. Mechanistically, the absence of HNF1alpha in diabetic-prone (sensitive) strains leads to postnatal defective islets growth that is remarkably restored in resistant strains. Our findings are relevant to human genetics since Moda1 is syntenic with a human locus identified by genome wide association studies of fasting glycemia in patients. Most importantly, our results show that a single genetic locus can completely suppress diabetes in Hnf1a-deficiency. PMID:27667715

  4. Homozygosity mapping of the gene for Chediak-Higashi syndrome to chromosome 1q42-q44 in a segment of conserved synteny that includes the mouse beige locus (bg)

    SciTech Connect

    Fukai, Kazuyoshi; Oh, Jangsuk; Karim, M.A.

    1996-09-01

    Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder characterized by hypopigmentation or oculocutaneous albinism and severe immunologic deficiency with neutropenia and lack of natural killer (NK) cell function. Most patients die in childhood from pyogenic infections or an unusual lymphoma-like condition. A hallmark of the disorder is giant inclusion bodies seen in all granule-containing cells, including granulocytes, lymphocytes, melanocytes, mast cells, and neurons. Similar ultrastructural abnormalities occur in the beige mouse, which thus has been suggested to be homologous to human CHS. High-resolution genetic mapping has indicated that the bg gene region of mouse chromosome 13 is likely homologous to the distal portion of human chromosome 1q. Accordingly, we carried out homozygosity mapping using markers derived from distal human chromosome 1q in four inbred families or probands with CHS. Our results indicate that the human CHS gene maps to an 18.8-cM interval in chromosome segment 1q42-q44 and that human CHS therefore is very likely homologous to mouse bg. 43 refs., 2 figs.

  5. Detection of a quantitative trait locus for both foliage and tuber resistance to late blight [Phytophthora infestans (Mont.) de Bary] on chromosome 4 of a dihaploid potato clone (Solanum tuberosum subsp. tuberosum).

    PubMed

    Bradshaw, John E; Hackett, Christine A; Lowe, Robert; McLean, Karen; Stewart, Helen E; Tierney, Irene; Vilaro, Marco D R; Bryan, Glenn J

    2006-09-01

    Linkage analysis, Kruskal-Wallis analysis, interval mapping and graphical genotyping were performed on a potato diploid backcross family comprising 120 clones segregating for resistance to late blight. A hybrid between the Solanum tuberosum dihaploid clone PDH247 and the long-day-adapted S. phureja clone DB226(70) had been crossed to DB226(70) to produce the backcross family. Eighteen AFLP primer combinations provided 186 and 123 informative maternal and paternal markers respectively, with 63 markers in common to both parents. Eleven microsatellite (SSR) markers proved useful for identifying chromosomes. Linkage maps of both backcross parents were constructed. The results of a Kruskal-Wallis analysis, interval mapping and graphical genotyping were all consistent with a QTL or QTLs for blight resistance between two AFLP markers 30 cM apart on chromosome 4, which was identified by a microsatellite marker. The simplest explanation of the results is a single QTL with an allele from the dihaploid parent conferring resistance to race 1, 4 of P. infestans in the foliage in the glasshouse and to race 1, 2, 3, 4, 6, 7 in the foliage in the field and in tubers from glasshouse raised plants. The QTL was of large effect, and explained 78 and 51% of the variation in phenotypic scores for foliage blight in the glasshouse and field respectively, as well as 27% of the variation in tuber blight. Graphical genotyping and the differences in blight scores between the parental clones showed that all of the foliage blight resistance is accounted for by chromosome 4, whereas undetected QTLs for tuber resistance probably exist on other chromosomes. Graphical genotyping also explained the lack of precision in mapping the QTL(s) in terms of lack of appropriate recombinant chromosomes.

  6. Meiotic chromosome structure and function in plants.

    PubMed

    Mainiero, Samantha; Pawlowski, Wojciech P

    2014-01-01

    Chromosome structure is important for many meiotic processes. Here, we outline 3 main determinants of chromosome structure and their effects on meiotic processes in plants. Cohesins are necessary to hold sister chromatids together until the first meiotic division, ensuring that homologous chromosomes and not sister chromatids separate during anaphase I. During meiosis in maize, Arabidopsis, and rice, cohesins are needed for establishing early prophase chromosome structure and recombination and for aligning bivalents at the metaphase plate. Condensin complexes play pivotal roles in controlling the packaging of chromatin into chromosomes through chromatin compaction and chromosome individualization. In animals and fungi, these complexes establish a meiotic chromosome structure that allows for proper recombination, pairing, and synapsis of homologous chromosomes. In plants, information on the role of condensins in meiosis is limited, but they are known to be required for successful completion of reproductive development. Therefore, we speculate that they play roles similar to animal and fungal condensins during meiosis. Plants generally have large and complex genomes due to frequent polyploidy events, and likely, condensins and cohesins organize chromosomes in such a way as to ensure genome stability. Hexaploid wheat has evolved a unique mechanism using a Ph1 locus-controlled chromosome organization to ensure proper chromosome pairing in meiosis. Altogether, studies on meiotic chromosome structure indicate that chromosome organization is not only important for chromatin packaging but also fulfills specific functions in facilitating chromosome interactions during meiosis, including pairing and recombination. PMID:25096046

  7. A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3.

    PubMed

    Lezirovitz, Karina; Maestrelli, Sylvia Regina Pedrosa; Cotrim, Nelson Henderson; Otto, Paulo A; Pearson, Peter L; Mingroni-Netto, Regina Celia

    2008-07-01

    Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

  8. The leukemia inhibitory factor receptor (LIFR) gene is located within a cluster of cytokine receptor loci on mouse chromosome 15 and human chromosome 5p12-p13

    SciTech Connect

    Gearing, D.P. ); Druck, T.; Huebner, K. ); Overhauser, J. ); Gilbert, D.J.; Copeland, N.G.; Jenkins, N.A. )

    1993-10-01

    The leukemia inhibitory factor receptor (LIFR) gene was localized to human chromosome 5p12-p13 by somatic cell hybrid analysis. Interspecific backcross analysis revealed that the murine locus was on chromosome 15 in a region of homology with human chromosome 5p. In both human and mouse genomes, the LIFR locus was linked to the genes encoding the receptors for interleukin-7, prolactin, and growth hormone. 13 refs., 1 fig.

  9. Image simulation using LOCUS

    SciTech Connect

    Strachan, J.D.; Roberts, J.A.

    1989-09-01

    The LOCUS data base program has been used to simulate images and to solve simple equations. This has been accomplished by making each record (which normally would represent a data entry)represent sequenced or random number pairs.

  10. Two-locus linkage analysis in multiple sclerosis (MS)

    SciTech Connect

    Tienari, P.J. Univ. of Helsinki ); Terwilliger, J.D.; Ott, J. ); Palo, J. ); Peltonen, L. )

    1994-01-15

    One of the major challenges in genetic linkage analyses is the study of complex diseases. The authors demonstrate here the use of two-locus linkage analysis in multiple sclerosis (MS), a multifactorial disease with a complex mode of inheritance. In a set of Finnish multiplex families, they have previously found evidence for linkage between MS susceptibility and two independent loci, the myelin basic protein gene (MBP) on chromosome 18 and the HLA complex on chromosome 6. This set of families provides a unique opportunity to perform linkage analysis conditional on two loci contributing to the disease. In the two-trait-locus/two-marker-locus analysis, the presence of another disease locus is parametrized and the analysis more appropriately treats information from the unaffected family member than single-disease-locus analysis. As exemplified here in MS, the two-locus analysis can be a powerful method for investigating susceptibility loci in complex traits, best suited for analysis of specific candidate genes, or for situations in which preliminary evidence for linkage already exists or is suggested. 41 refs., 6 tabs.

  11. Heteromorphic variants of chromosome 9

    PubMed Central

    2013-01-01

    Background Heterochromatic variants of pericentromere of chromosome 9 are reported and discussed since decades concerning their detailed structure and clinical meaning. However, detailed studies are scarce. Thus, here we provide the largest ever done molecular cytogenetic research based on >300 chromosome 9 heteromorphism carriers. Results In this study, 334 carriers of heterochromatic variants of chromosome 9 were included, being 192 patients from Western Europe and the remainder from Easter-European origin. A 3-color-fluorescence in situ hybridization (FISH) probe-set directed against for 9p12 to 9q13~21.1 (9het-mix) and 8 different locus-specific probes were applied for their characterization. The 9het-mix enables the characterization of 21 of the yet known 24 chromosome 9 heteromorphic patterns. In this study, 17 different variants were detected including five yet unreported; the most frequent were pericentric inversions (49.4%) followed by 9qh-variants (23.9%), variants of 9ph (11.4%), cenh (8.2%), and dicentric- (3.8%) and duplication-variants (3.3%). For reasons of simplicity, a new short nomenclature for the yet reported 24 heteromorphic patterns of chromosome 9 is suggested. Six breakpoints involved in four of the 24 variants could be narrowed down using locus-specific probes. Conclusions Based on this largest study ever done in carriers of chromosome 9 heteromorphisms, three of the 24 detailed variants were more frequently observed in Western than in Eastern Europe. Besides, there is no clear evidence that infertility is linked to any of the 24 chromosome 9 heteromorphic variants. PMID:23547710

  12. Comparative mapping reveals partial conservation of synteny at the apomixis locus in Paspalum spp.

    PubMed

    Pupilli, F; Martinez, E J; Busti, A; Calderini, O; Quarin, C L; Arcioni, S

    2004-01-01

    In plants, gametophytic apomixis is a form of asexual reproduction that leads to the formation of seed-derived offspring that are genetically identical to the mother plant. A common set of RFLP markers, including five rice anchor markers previously shown to be linked to apomixis in Paspalum simplex, were used to detect linkage with apomixis in P. notatum and P. malacophyllum. A comparative map of the region around the apomixis locus was constructed for the three Paspalum species, and compared to the rice map. The locus that controls apomixis in P. simplex was almost completely conserved in the closely related species P. malacophyllum, whereas it was only partially represented in the distantly related species P. notatum. Although strong synteny of markers was noted between this locus and a portion of rice chromosome 12 in both P. simplex and P. malacophyllum, the same locus in P. notatum was localized to a hybrid chromosome which carries markers that map to rice chromosomes 2 and 12. All three Paspalum species showed recombination suppression at the apomixis locus; in the case of P. notatum, this might be due to a heterozygosity for a translocation that most probably negatively interferes with chromosomal pairing near the locus. A common set of markers that show linkage with apomixis in all three Paspalum species define a portion of the apomixis-controlling locus that is likely to contain genes critical for apomictic reproduction.

  13. 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.

  14. Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human

    SciTech Connect

    Mbikay, M.; Seidah, N.G.; Chretien, M.

    1995-03-01

    The genes for three subtilisin/kexin-like proprotein convertases, PC4, PC5, and PACE4, were mapped in the mouse by RFLP analysis of a DNA panel from a (C57BL/6JEi x SPRET/Ei) F{sub 1} x SPRET/Ei backcross. The chromosomal locations of the human homologs were determined by Southern blot analysis of a DNA panel from human-rodent somatic cell hybrids, most of which contained a single human chromosome each. The gene for PC4 (Pcsk4 locus) mapped to mouse chromosome 10, close to the Adn (adipsin, a serine protease) locus and near the Amh (anti-Mullerian hormone) locus; in a human, the gene was localized to chromosome 19. The gene for PC5 (Pcsk5 locus) mapped to mouse chromosome 19 close to the Lpc1 (lipoacortin-1) locus and, in human, was localized to chromosome 9. The gene for PACE4 (Pcsk6 locus) mapped to mouse chromosome 7, at a distance of 13 cM from the Pcsk3 locus, which specifies furin, another member of this family of enzymes previoulsy mapped to this chromosome. This is in concordance with the known close proximity of these two loci in the homologous region on human chromosome 15q25-qter. Pcsk3 and Pcsk6 mapped to a region of mouse chromosome 7 that has been associated cytogenetically with postnatal lethality in maternal disomy, suggesting that these genes might be candidates for imprinting. 43 refs., 3 figs., 2 tabs.

  15. Coordinate regulation of two genes encoding gluconeogenic enzymes by the trans-dominant locus Tse-1.

    PubMed Central

    Lem, J; Chin, A C; Thayer, M J; Leach, R J; Fournier, R E

    1988-01-01

    Tissue-specific extinguisher-1 (Tse-1) is a mouse genetic locus that can repress liver-specific tyrosine aminotransferase gene expression in trans. To search for other Tse-1-responsive genes, hepatoma microcell hybrids retaining mouse chromosome 11 or human chromosome 17, containing murine Tse-1 and human TSE1, respectively, were screened for expression of liver-specific mRNAs. While most liver gene activity was unaffected in such hybrids, phosphoenolpyruvate carboxykinase and tyrosine aminotransferase gene expression was coordinately repressed in these clones. Extinction of both genes was apparently mediated by a single genetic locus that resides on human chromosome 17. Images PMID:2902627

  16. 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…

  17. A new EcoRI polymorphism at the D21S13 locus.

    PubMed

    Pulst, S M; Korenberg, J R; Greenwald, J; Carbone, M

    1990-05-01

    The D21S13 locus has shown linkage to a gene for familial Alzheimer disease (FAD) on chromosome 21 (St. George-Hyslop et al. 1987). The limited informativeness of probes for this locus have hindered precise mapping of the FAD locus and analysis of nonallelic heterogeneity in FAD (Schellenberg et al. 1988; St. George-Hyslop et al. 1987). We describe a new EcoRI polymorphism at the D21S13 locus that may be useful for the further study of FAD families.

  18. Genetic analysis of the claret locus of Drosophila melanogaster

    SciTech Connect

    Sequeira, W.; Nelson, C.R.; Szauter, P. )

    1989-11-01

    The claret (ca) locus of Drosophila melanogaster comprises two separately mutable domains, one responsible for eye color and one responsible for proper disjunction of chromosomes in meiosis and early cleavage divisions. Previously isolated alleles are of three types: (1) alleles of the claret (ca) type that affect eye color only, (2) alleles of the claret-nondisjunctional (ca{sup nd}) type that affect eye color and chromosome behavior, and (3) a meiotic mutation, non-claret disjunctional (ncd), that affects chromosome behavior only. In order to investigate the genetic structure of the claret locus, the authors have isolated 19 radiation-induced alleles of claret on the basis of the eye color phenotype. Two of these 19 new alleles are of the ca{sup nd} type, while 17 are of the ca type, demonstrating that the two domains do not often act as a single target for mutagenesis. This suggests that the two separately mutable functions are likely to be encoded by separate or overlapping genes rather than by a single gene. One of the new alleles of the ca{sup nd} type is a chromosome rearrangement with a breakpoint at the position of the claret locus. If this breakpoint is the cause of the mutant phenotype and there are no other mutations associated with the rearrangement, the two functions must be encoded by overlapping genes.

  19. Schizophrenia and chromosomal deletions

    SciTech Connect

    Lindsay, E.A.; Baldini, A.; Morris, M. A.

    1995-06-01

    Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.

  20. 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 ...

  1. Noninvolvement of the X chromosome in radiation-induced chromosome translocations in the human lymphoblastoid cell line TK6

    SciTech Connect

    Jordan, R.; Schwartz, J.L. )

    1994-03-01

    Fluorescence in situ hybridization procedures were used to examine the influence of chromosome locus on the frequency and type of chromosome aberrations induced by [sup 60]Co [gamma] rays in the human lymphoblastoid cell line TK6. Aberrations involving the X chromosome were compared to those involving the similarly sized autosome chromosome 7. When corrected for DNA content, acentric fragments were induced with equal frequency in the X and 7 chromosomes. Dose-dependent increases in chromosomal interchanges involving chromosome 7 were noted, and the frequencies of balanced translocations and dicentrics produced were approximately equal. Chromosome interchanges involving the X chromosome were rare and showed no apparent dose dependence. Thus, while chromosomes 7 and X are equally sensitive to the induction of chromosome breaks, the X chromosome is much less likely to interact with autosomes than chromosome 7. The noninvolvement of the X chromosome in translocations with autosomes may reflect a more peripheral and separate location for the X chromosome in the mammalian nucleus. 20 refs., 2 figs., 1 tab.

  2. Sequence analysis of a near-subtelomeric 35.4 kb DNA segment on the right arm of chromosome VII from Saccharomyces cerevisiae carrying the MAL1 locus reveals 15 complete open reading frames, including ZUO1, BGL2 and BIO2 genes and an ABC transporter gene.

    PubMed

    Volckaert, G; Voet, M; Robben, J

    1997-03-15

    The nucleotide sequence of 35,400 bp at approximately 10 kb from the right telomere of chromosome VII was determined. The segment contains the MAL1 locus, one of the five unlinked loci sufficient for maltose utilization. Until now, each of these loci was considered to contain three genes (for regulator, permease and alpha-glucosidase), but a fourth gene, presumably an extra alpha-glucosidase gene, was found at MAL1 adjacent to the usual cluster of three genes. The two glucosidase genes are present in opposite orientation, forming an inverted repeat structure. In addition to the four genes at MAL1, there are 11 complete, non-overlapping open reading frames (ORFs) longer than 300 bp in the sequence presented here. A new ABC transporter gene (YGR281w), required for oligomycin resistance was found (YOR1; Katzman et al., 1995), and the previously sequenced BGL2 (YGR282c), ZUO1 (YGR285c) and BIO2 (YGR286c) genes were located. The sequence of BIO2, a biotin synthetase gene, required substantial correction and the size of Bio2p is 375, rather than 356, amino acids. Two ORFs show rather weak similarities to animal genes: YGR278w to an unknown ORF of Caenorhabditis elegans and YGR284c to the murine Surf-4, a member of a cluster of at least four housekeeping genes. The remaining five ORFs do not encode known functions, but three of these show weak to high similarities to other ORFs in the Saccharomyces cerevisiae genome and one (YGR280c) codes for a particularly lysine-rich protein.

  3. Transposable elements and early evolution of sex chromosomes in fish.

    PubMed

    Chalopin, Domitille; Volff, Jean-Nicolas; Galiana, Delphine; Anderson, Jennifer L; Schartl, Manfred

    2015-09-01

    In many organisms, the sex chromosome pair can be recognized due to heteromorphy; the Y and W chromosomes have often lost many genes due to the absence of recombination during meiosis and are frequently heterochromatic. Repetitive sequences are found at a high proportion on such heterochromatic sex chromosomes and the evolution and emergence of sex chromosomes has been connected to the dynamics of repeats and transposable elements. With an amazing plasticity of sex determination mechanisms and numerous instances of independent emergence of novel sex chromosomes, fish represent an excellent lineage to investigate the early stages of sex chromosome differentiation, where sex chromosomes often are homomorphic and not heterochromatic. We have analyzed the composition, distribution, and relative age of TEs from available sex chromosome sequences of seven teleost fish. We observed recent bursts of TEs and simple repeat accumulations around young sex determination loci. More strikingly, we detected transposable element (TE) amplifications not only on the sex determination regions of the Y and W sex chromosomes, but also on the corresponding regions of the X and Z chromosomes. In one species, we also clearly demonstrated that the observed TE-rich sex determination locus originated from a TE-poor genomic region, strengthening the link between TE accumulation and emergence of the sex determination locus. Altogether, our results highlight the role of TEs in the initial steps of differentiation and evolution of sex chromosomes.

  4. 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

  5. Mapping of panda plumage color locus on the microsatellite linkage map of the Japanese quail

    PubMed Central

    Miwa, Mitsuru; Inoue-Murayama, Miho; Kobayashi, Naoki; Kayang, Boniface Baboreka; Mizutani, Makoto; Takahashi, Hideaki; Ito, Shin'ichi

    2006-01-01

    Background Panda (s) is an autosomal recessive mutation, which displays overall white plumage color with spots of wild-type plumage in the Japanese quail (Coturnix japonica). In a previous study, the s locus was included in the same linkage group as serum albumin (Alb) and vitamin-D binding protein (GC) which are mapped on chicken (Gallus gallus) chromosome 4 (GGA4). In this study, we mapped the s locus on the microsatellite linkage map of the Japanese quail by linkage analysis. Results Segregation data on the s locus were obtained from three-generation families (n = 106). Two microsatellite markers derived from the Japanese quail chromosome 4 (CJA04) and three microsatellite markers derived from GGA4 were genotyped in the three-generation families. We mapped the s locus between GUJ0026 and ABR0544 on CJA04. By comparative mapping with chicken, this locus was mapped between 10.0 Mb and 14.5 Mb region on GGA4. In this region, the endothelin receptor B subtype 2 gene (EDNRB2), an avian-specific paralog of the mammalian endothelin receptor B gene (EDNRB), is located. Because EDNRB is responsible for aganglionic megacolon and spot coat color in mouse, rat and equine, EDNRB2 is suggested to be a candidate gene for the s locus. Conclusion The s locus and the five microsatellite markers were mapped on CJA04 of the Japanese quail. EDNRB2 was suggested to be a candidate gene for the s locus. PMID:16405738

  6. Molecular organization of the cut locus of Drosophila melanogaster.

    PubMed

    Jack, J W

    1985-10-01

    Mutations of the cut locus (ct) of Drosophila can be divided into four groups based on their phenotypes and complementation patterns. Each group alters the phenotype of a different set of tissues. Two hundred kilobases of ct DNA, located in 7B1-2, have been cloned by chromosomal walking, and the cloned sequences have been used to analyze more than 40 mutants. Based on the location of transposable element mutations and the extent of deficiencies and an inversion, four cut locus regions can be defined. Mutations in each region affect the phenotype of a different set of tissues. The most centromere proximal region contains mutations that are null for cut locus function. Within individual regions, a higher level of organization can be detected. PMID:2996782

  7. 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.

  8. On the Components of Segregation Distortion in Drosophila Melanogaster. IV. Construction and Analysis of Free Duplications for the Responder Locus

    PubMed Central

    Brittnacher, J. G.; Ganetzky, B.

    1989-01-01

    Male Drosophila heterozygous for an SD-bearing second chromosome and a normal homolog preferentially transmit the SD chromosome to their offspring. The distorted transmission involves the induced dysfunction of the sperm that receive the SD(+) chromosome. The loci on the SD chromosome responsible for causing distortion are the Sd locus the the E(SD) locus. Their target of action on the SD(+) chromosome is the Rsp(s) locus. Previous studies of Rsp(s) indicated that deletion of this locus rendered a chromosome insensitive to the action of SD and mapped Rsp(s) physically within the centric heterochromatin of 2R. In this study we have constructed a collection of marked free duplications for the centromeric region of a second chromosome that carried Rsp(s). The heterochromatic extent of each duplication as well as its sensitivity to distortion was determined. We found that Rsp(s) is the most proximal known locus within the 2R heterochromatin. Furthermore, our results demonstrate that the presence of Rsp(s) is not only necessary but sufficient to confer sensitivity to distortion irrespective of its association with an intact second chromosome or one that pairs meiotically with an SD chromosome. By use of these duplications we increased the usual dosage of Rsp(s) relative to SD to determine whether there was any competition for limited amounts of SD [and/or E(SD)] product. When two Rsp(s)-bearing chromosomes are present within the same spermatocyte nucleus an SD chromosome is capable of causing efficient distortion of both. However, at least in some cases the degree of distortion against a given Rsp(s) was reduced by the presence of an extra dose of Rsp(s) indicating that there was some competition between them. The bearing of these results on present models of segregation distortion are discussed. PMID:2498160

  9. The pronatriodilatin gene is located on the distal short arm of human chromosome 1 and on mouse chromosome 4.

    PubMed

    Yang-Feng, T L; Floyd-Smith, G; Nemer, M; Drouin, J; Francke, U

    1985-11-01

    Atrial natriuretic factors (ANF) are polypeptides having natriuretic, diuretic, and smooth muscle-relaxing activities that are synthesized from a single larger precursor: pronatriodilatin. Chromosomal assignment of the gene coding for human pronatriodilatin was accomplished by in situ hybridization of a [3H]-labeled pronatriodilatin probe to human chromosome preparations and by Southern blot analysis of somatic cell hybrid DNAs with normal and rearranged chromosomes 1. The human pronatriodilatin gene was mapped to the distal short arm of chromosome 1, in band 1p36. Southern blot analysis of mouse X Chinese hamster somatic cell hybrids was used to assign the mouse pronatriodilatin gene to chromosome 4. This assignment adds another locus to the conserved syntenic group of homologous genes located on the distal half of the short arm of human chromosome 1 and on mouse chromosome 4.

  10. Molecular mapping of chromosomes 17 and X

    SciTech Connect

    Barker, D.F.

    1989-01-01

    The basic aims of this project are the construction of high density genetic maps of chromosomes 17 and X and the utilization of these maps for the subsequent isolation of a set of physically overlapping DNA segment clones. The strategy depends on the utilization of chromosome specific libraries of small (1--15 kb) segments from each of the two chromosomes. Since the time of submission of our previous progress report, we have refined the genetic map of markers which we had previously isolated for chromosome 17. We have completed our genetic mapping in CEPH reference and NF1 families of 15 markers in the pericentric region of chromosome 17. Physical mapping results with three probes, were shown be in very close genetic proximity to the NF1 gene, with respect to two translocation breakpoints which disrupt the activity of the gene. All three of the probes were found to lie between the centromere and the most proximal translocation breakpoint, providing important genetic markers proximal to the NF1 gene. Our primary focus has shifted to the X chromosome. We have isolated an additional 30 polymorphic markers, bringing the total number we have isolated to over 80. We have invested substantial effort in characterizing the polymorphisms at each of these loci and constructed plasmid subclones which reveal the polymorphisms for nearly all of the loci. These subclones are of practical value in that they produce simpler and stronger patterns on human genomic Southern blots, thus improving the efficiency of the genetic mapping experiments. These subclones may also be of value for deriving DNA sequence information at each locus, necessary for establishing polymerase chain reaction primers specific for each locus. Such information would allow the use of each locus as a sequence tagged site.

  11. Identifying a novel locus for psoriatic arthritis

    PubMed Central

    Budu-Aggrey, Ashley; Bowes, John

    2016-01-01

    A number of studies have identified genetic risk loci for PsA, the majority of which also confer risk for psoriasis. The stronger heritability of PsA in comparison with psoriasis suggests that there should be risk loci that are specific for PsA. Identifying such loci could potentially inform therapy development to provide more effective treatments for PsA patients, especially with a considerable proportion being non-responsive to current therapies. Evidence of a PsA-specific locus has been previously found at HLA-B27 within the MHC region. A recent study has provided evidence of non-HLA risk loci that are specific for PsA at IL23R, PTPN22 and on chromosome 5q31. Functional characterization of these loci will provide further understanding of the pathways underlying PsA, and enable us to apply genetic findings for patient benefit. PMID:26255310

  12. On the Components of Segregation Distortion in DROSOPHILA MELANOGASTER. II. Deletion Mapping and Dosage Analysis of the SD Locus

    PubMed Central

    Brittnacher, John G.; Ganetzky, Barry

    1983-01-01

    Segregation distorter (SD) chromosomes are preferentially transmitted to offspring from heterozygous SD/SD+ males owing to the induced dysfunction of the SD+-bearing sperm. This phenomenon involves at least two major loci: the Sd locus whose presence is necessary for distortion to occur and the Rsp locus which acts as the site of Sd action. Several additional loci on SD chromosomes enhance distortion.—In a previous study deletions were used to map the Sd locus and to determine some of its properties. We have extended this analysis with the isolation and characterization of 14 new deletions in the Sd region. From our results we conclude (1) SD chromosomes contain a single Sd locus located in region 37D2-6 of the salivary gland chromosome map. Deletion of this locus in any of three SD chromosomes now studied results in complete loss of ability to distort a sensitive chromosome; (2) the reduced male fecundity observed in many homozygous SD or SDi/SDj combinations is due at least in part to the action of the Sd locus. The fecundity of these males can be substantially increased by deletion of one Sd locus. Thus, it is the presence of two doses of Sd rather than the absence of Sd+ that produces the lowered male fecundity in SD homozygotes; (3) Sd behaves as a neomorph, whereas Sd+, if it exists at all, is amorphic with respect to segregation distortion; (4) these results support a model in which the Sd product is made in limiting amounts and the interaction of this product with the Rsp locus causes sperm dysfunction. The Sd product appears to act preferentially at Rsps (sensitive-Responder) but may also act at Rspi (insensitive-Responder). PMID:17246120

  13. 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

  14. 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.

  15. A Sex Chromosomal Restriction-Fragment-Length Marker Linked to Melanoma-Determining Tu Loci in Xiphophorus

    PubMed Central

    Schartl, M.

    1988-01-01

    In Xiphophorus, the causative genetic information for melanoma formation has been assigned by classical genetics to chromosomal loci, which are located on the sex chromosomes. In our attempts to molecularly clone these melanoma-determining loci, named Tu, we have looked for restriction-fragment-length markers (RFLMs) linked to the Tu loci. These RFLMs should be useful in obtaining a physical map of a Tu locus, which will aid in the cloning of the corresponding sequences. DNA samples from various Xiphophorus strains and hybrids including those bearing different Tu wild-type, deletion and translocation chromosomes, were screened for the presence of random RFLMs using homologous or heterologous sequences as hybridization probes. We find an EcoRI restriction fragment which shows limited crosshybridization to the v-erb B gene--but not representing the authentic c-erb B gene of Xiphophorus--to be polymorphic with respect to different sex chromosomes. Linkage analysis revealed that a 5-kb fragment is linked to the Tu-Sd locus on the X chromosome, a 7-kb fragment is linked to the Tu-Sr locus on the Y chromosome, both of Xiphophorus maculatus, and that a 12-kb fragment is linked to the Tu-Li locus on the X chromosome of Xiphophorus variatus. Using different chromosomal mutants this RFLM has been mapped to a frequent deletion/translocation breakpoint of the X chromosome, less than 0.3 cM apart from the Tu locus. PMID:2841190

  16. A sex chromosomal restriction-fragment-length marker linked to melanoma-determining Tu loci in Xiphophorus.

    PubMed

    Schartl, M

    1988-07-01

    In Xiphophorus, the causative genetic information for melanoma formation has been assigned by classical genetics to chromosomal loci, which are located on the sex chromosomes. In our attempts to molecularly clone these melanoma-determining loci, named Tu, we have looked for restriction-fragment-length markers (RFLMs) linked to the Tu loci. These RFLMs should be useful in obtaining a physical map of a Tu locus, which will aid in the cloning of the corresponding sequences. DNA samples from various Xiphophorus strains and hybrids including those bearing different Tu wild-type, deletion and translocation chromosomes, were screened for the presence of random RFLMs using homologous or heterologous sequences as hybridization probes. We find an EcoRI restriction fragment which shows limited crosshybridization to the v-erb B gene--but not representing the authentic c-erb B gene of Xiphophorus--to be polymorphic with respect to different sex chromosomes. Linkage analysis revealed that a 5-kb fragment is linked to the Tu-Sd locus on the X chromosome, a 7-kb fragment is linked to the Tu-Sr locus on the Y chromosome, both of Xiphophorus maculatus, and that a 12-kb fragment is linked to the Tu-Li locus on the X chromosome of Xiphophorus variatus. Using different chromosomal mutants this RFLM has been mapped to a frequent deletion/translocation breakpoint of the X chromosome, less than 0.3 cM apart from the Tu locus. PMID:2841190

  17. Gene targeting for chromosome engineering applications in eukaryotic cells.

    PubMed

    Lyznik, Leszek A; Dress, Virginia

    2008-01-01

    As biotechnology advances, there is an increasing need to develop new technologies that may assist in more precise genetic engineering manipulations. Whether a placement of single genes in the proper chromosomal context, stacking a number of genes in the same chromosomal locus, rearrangement of existing chromosomal elements, or a global reconfiguration of the chromosomal structures is contemplated, the new genetic tools being developed provide technical capabilities to achieve goals that were only theoretical not long ago. We use examples of recent patent literature (issued patents and published patent applications) to illustrate trends in this fast advancing area of genetic technology. If one wants to engage in the development and utilization of such technologies, the complexity of genetic manipulations requires a careful evaluation and navigation across the legal/patent landscape of chromosomal modification/remodeling. While this review is mostly focused on the basic laboratory tools of chromosomal manipulations, their specific applications for biomedical, pharmaceutical, or agricultural purposes may deserve an additional compilation.

  18. Genome structure and primitive sex chromosome revealed in Populus

    SciTech Connect

    Tuskan, Gerald A; Yin, Tongming; Gunter, Lee E; Blaudez, D

    2008-01-01

    We constructed a comprehensive genetic map for Populus and ordered 332 Mb of sequence scaffolds along the 19 haploid chromosomes in order to compare chromosomal regions among diverse members of the genus. These efforts lead us to conclude that chromosome XIX in Populus is evolving into a sex chromosome. Consistent segregation distortion in favor of the sub-genera Tacamahaca alleles provided evidence of divergent selection among species, particularly at the proximal end of chromosome XIX. A large microsatellite marker (SSR) cluster was detected in the distorted region even though the genome-wide distribute SSR sites was uniform across the physical map. The differences between the genetic map and physical sequence data suggested recombination suppression was occurring in the distorted region. A gender-determination locus and an overabundance of NBS-LRR genes were also co-located to the distorted region and were put forth as the cause for divergent selection and recombination suppression. This hypothesis was verified by using fine-scale mapping of an integrated scaffold in the vicinity of the gender-determination locus. As such it appears that chromosome XIX in Populus is in the process of evolving from an autosome into a sex chromosome and that NBS-LRR genes may play important role in the chromosomal diversification process in Populus.

  19. Progress towards complete genetic and physical maps of chromosome 3

    SciTech Connect

    Naylor, S.L.; Munoz, C.; Badura, M.

    1994-09-01

    Human chromosome 3 contains 210 million base pairs and approximately 7,000 genes. Our center is directed towards making genetic and physical maps of chromosome 3 with the goal of a YAC contig of the chromosome and 2500 STSs. Markers are first binned into 23 regions of chromosome 3 using framework somatic cell hybrids. To date, STSs for 259 microsatellite and 63 genes have been placed into bins. 125 polymorphic simple sequences repeat (SSR) markers were genetically mapped to chromosome 3 using PCR-based genotyping of the CEPH reference families. This genetic map spans 271 cM (sex averaged). A chromosome 3-specific radiation-reduced somatic cell hybrid panels has been constructed to obtain higher resolution map order information. With the map locations of these markers as a guide, 226 loci were screened using PCR-based hierarchial screening of the CEPH Mark I and Mark IV-VII yeast artificial chromosome (YAC) libraries. YAC contigs which are ordered on the chromosome consist of 33 multi-locus contigs covering 80 cM and single locus contigs accounting for 62 cM. We have isolated approximately 1000 YACs by this method covering 65% of chromosome 3. IRS-PCR screening of the CEPH YAC library has yielded several thousand more chromosome 3 YACs which are being screened with the STSs to integrate them into contigs. FISH analysis on a random sampling of 60 YACs from the long arm was performed to assess the degree of chimerism. 40% of the YACs hybridized to the map locations predicted by the STSs used in their isolation. 30% were obviously chimeric while 40% hybridized uniquely to the predicted region as well as nonspecifically to centromeres and telomeres. This integrated approach to constructing a map of chromosome 3 will result in a reliably ordered YAC contig for this chromosome.

  20. Evidence that the Saethre-Chotzen syndrome locus lies between D7S664 and D7S507, by genetic analysis and detection of a microdeletion in a patient

    SciTech Connect

    Lewanda, A.F.; Jerald, H.; Taylor, E.; Jabs, E.W.; Green, E.D.; Weissenbach, J.; Summar, M.L.; Phillips, J.A. III; Cohen, M.; Feingold, M.

    1994-12-01

    The locus for Saethre-Chotzen syndrome, a common autosomal dominant disorder of craniosynostosis and digital anomalies, was previously mapped to chromosome 7p between D7S513 and D7S516. We used linkage and haplotype analyses to narrow the disease locus to an 8-cM region between D7S664 and D7S507. The tightest linkage was to locus D7S664 (Z = 7.16, {theta} = .00). chromosomes from a Saethre-Chotzen syndrome patient with t(2;7) (p23;p22) were used for in situ hybridization with YAC clones containing D7S664 and D7S507. The D7S664 locus was found to lie distal to the 7p22 breakpoint, and the D7S507 locus was deleted from the translocation chromosomes. These genetic and physical mapping data independently show that the disease locus resides in this interval.

  1. Mitotic recombination of chromosome 17 in astrocytomas

    SciTech Connect

    James, C.D.; Carlbom, E.; Nordenskjold, M.; Collins, V.P.; Cavenee, W.K. )

    1989-04-01

    Allelic combinations at seven loci on human chromosome 17 defined by restriction fragment length polymorphisms were determined in tumor and normal tissues from 35 patients with gliomas. Loss of constitutional heterozygosity at one or more of these loci was observed in 8 of the 24 tumors displaying astrocytic differentiation and in the single primitive neuroectodermal tumor examined. The astrocytomas showing these losses included examples of each adult malignancy grade of the disease, including glioblastoma (malignancy grade IV), and seven of them demonstrated concurrent maintenance of heterozygosity for at least one chromosome 17 locus. Determination of allele dosage together with the genotypic data indicated that the tumor chromosomes 17 were derived by mitotic recombination in 7 of the 9 cases with shared homozygosity of the region 17p11.2-ptr in all cases. In contrast, tumors of oligodendrocytic, ependymal, or mixed cellular differentiation did not exhibit loss of alleles at any of the loci examined. These data suggest that the somatic attainment of homozygosity for loci on chromosome 17p is frequently associated with the oncogenesis of central nervous system tumors, particularly those showing solely astrocytic differentiation, and that mitotic recombination mapping is a useful approach towards the subregional localization of a locus whose rearrangement is involved in this disease.

  2. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    SciTech Connect

    Mullan, M.; Bennett, C.; Figueredo, C.; Crawford, F.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.

  3. Independent stratum formation on the avian sex chromosomes reveals inter-chromosomal gene conversion and predominance of purifying selection on the W chromosome.

    PubMed

    Wright, Alison E; Harrison, Peter W; Montgomery, Stephen H; Pointer, Marie A; Mank, Judith E

    2014-11-01

    We used a comparative approach spanning three species and 90 million years to study the evolutionary history of the avian sex chromosomes. Using whole transcriptomes, we assembled the largest cross-species dataset of W-linked coding content to date. Our results show that recombination suppression in large portions of the avian sex chromosomes has evolved independently, and that long-term sex chromosome divergence is consistent with repeated and independent inversions spreading progressively to restrict recombination. In contrast, over short-term periods we observe heterogeneous and locus-specific divergence. We also uncover four instances of gene conversion between both highly diverged and recently evolved gametologs, suggesting a complex mosaic of recombination suppression across the sex chromosomes. Lastly, evidence from 16 gametologs reveal that the W chromosome is evolving with a significant contribution of purifying selection, consistent with previous findings that W-linked genes play an important role in encoding sex-specific fitness.

  4. Analysis of Single Locus Trajectories for Extracting In Vivo Chromatin Tethering Interactions

    PubMed Central

    Amitai, Assaf; Toulouze, Mathias; Dubrana, Karine; Holcman, David

    2015-01-01

    Is it possible to extract tethering forces applied on chromatin from the statistics of a single locus trajectories imaged in vivo? Chromatin fragments interact with many partners such as the nuclear membrane, other chromosomes or nuclear bodies, but the resulting forces cannot be directly measured in vivo. However, they impact chromatin dynamics and should be reflected in particular in the motion of a single locus. We present here a method based on polymer models and statistics of single trajectories to extract the force characteristics and in particular when they are generated by the gradient of a quadratic potential well. Using numerical simulations of a Rouse polymer and live cell imaging of the MAT-locus located on the yeast Saccharomyces cerevisiae chromosome III, we recover the amplitude and the distance between the observed and the interacting monomer. To conclude, the confined trajectories we observed in vivo reflect local interaction on chromatin. PMID:26317360

  5. Fixing the broken system of genetic locus symbols

    PubMed Central

    Lohmann, Katja; Lang, Anthony; Klein, Christine

    2012-01-01

    Originally, locus symbols (e.g., DYT1) were introduced to specify chromosomal regions that had been linked to a familial disorder with a yet unknown gene. Symbols were systematically assigned in a numerical series to designate mapped loci for a specific phenotype or group of phenotypes. Since the system of designating and using locus symbols was originally established, both our knowledge and our techniques of gene discovery have evolved substantially. The current system has problems that are sources of confusion, perpetuate misinformation, and misrepresent the system as a useful reference tool for a list of inherited disorders of a particular phenotypic class. These include erroneously assigned loci, duplicated loci, missing symbols, missing loci, unconfirmed loci in a consecutively numbered system, combining causative genes and risk factor genes in the same list, and discordance between phenotype and list assignment. In this article, we describe these problems and their impact, and propose solutions. The system could be significantly improved by creating distinct lists for clinical and research purposes, creating more informative locus symbols, distinguishing disease-causing mutations from risk factors, raising the threshold of evidence prior to assigning a locus symbol, paying strict attention to the predominant phenotype when assigning symbols lists, and having a formal system for reviewing and continually revising the list that includes input from both clinical and genetics experts. PMID:22454269

  6. A cis-acting sequence involved in chromosome segregation in Escherichia coli.

    PubMed

    Fekete, Richard A; Chattoraj, Dhruba K

    2005-01-01

    Eukaryotic chromosomes contain a locus, the centromere, at which force is applied to separate replicated chromosomes. A centromere analogue is also found in some bacterial plasmids and chromosomes, although not yet identified in the well-studied Escherichia coli chromosome. We aimed to identify centromere-like sequences in E. coli with the premise that such sequences would be the first to migrate towards the cell poles, away from the cell centre where DNA replication is believed to occur. We have labelled different loci on the chromosome by integrating arrays of binding sites for LacI-EYFP and phage lambdacI-ECFP and supplying these fusion proteins in trans. Comparison of such pairs of loci suggests the presence of a centromere-like site close to the origin of replication. Polar migration of the site was dependent on migS, a locus recently implicated in chromosome migration, thus providing strong support for migS being the E. coli centromere.

  7. The linkage map of sheep Chromosome 6 compared with orthologous regions in other species.

    PubMed

    Lord, E A; Lumsden, J M; Dodds, K G; Henry, H M; Crawford, A M; Ansari, H A; Pearce, P D; Maher, D W; Stone, R T; Kappes, S M; Beattie, C W; Montgomery, G W

    1996-05-01

    The genetic linkage map of sheep Chromosome (Chr) 6 has been extended to include 35 loci with the addition of 11 RFLP and 12 microsatellite loci. The sex-averaged linkage map now spans 154 cM from phosphodiesterase cyclic GMP beta polypeptide (PDE6B) to OarCP125, an anonymous sheep microsatellite. The male and female map lengths, at 180 cM and 132 cM respectively, did not differ significantly. The physical assignment of PDE6B to Chr 6q33-qter orientates the linkage map on sheep Chr 6 with PDE6B near the telomere and OarCP125 towards the centromere. The order and genetic distances between loci are similar for the sheep Chr 6 and cattle Chr 6 maps, except for the position of the casein genes. The sheep Chr 6 linkage map is also comparable to portions of human Chr 4, mouse Chrs 5 and 3, and pig Chr 8. The synteny between sheep Chr 6 and human Chr 4 has been extended from PDE6B (4p16.3) to epidermal growth factor (EGF, 4q25-q27). However, a region from platelet-derived growth factor receptor alpha polypeptide (PDGFRA) to bone morphogenetic protein 3 (BMP3), which spans 19 cM on sheep Chr 6, appears to be inverted with respect to the human and mouse loci. Other differences in the gene order between sheep, pig, and mouse suggest more complex rearrangements.

  8. Gene differences between third-chromosome inversions of Drosophila pseudobscura.

    PubMed

    Prakash, S

    1976-12-01

    Associations of alleles of the acid phosphatase-3 locus with the different third-chromosome inversions from different populations of D. pseudoobscura are described. We observe only the allele AP-3(1.0) in the Standard and Arrowhead inversions and the allele AP-3.98 in the Santa Cruz, Treeline, Cuernavaca and the Pikes Peak arrangements. The Chiricahua gene arrangement is polymorphic.

  9. Paroxysmal dystonic choreoathetosis: Tight linkage to chromosome 2q

    SciTech Connect

    Fink, J.K.; Rainier, S.; Wilkowski, J.; Jones, S.M.

    1996-07-01

    Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus. 28 refs., 2 figs., 1 tab.

  10. Genetic defect causing familial Alzheimer's disease maps on chromosome 21

    SciTech Connect

    St. George-Hyslop, P.H.; Tanzi, R.E.; Polinsky, R.J.; Haines, J.L.; Nee, L.; Watkins, P.C.; Myers, R.H.; Feldman, R.G.; Pollen, D.; Drachman, D.; Growdon, J.

    1987-02-20

    Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

  11. The physical gene Hsp70 map on polytene chromosomes of Anopheles darlingi from the Brazilian Amazon.

    PubMed

    Rafael, Míriam Silva; Tadei, Wanderli Pedro; Hunter, Fiona F

    2004-05-01

    In situ hybridization was used to determine the physical location of the Hsp70 genes in salivary polytene chromosomes of Anopheles darlingi from Manaus and Macapá, Brazil, and to assess the usefulness of the Hsp70 locus as a genetic marker in A. darlingi populations. In both populations, the double markings corresponding to the Hsp70-12A and Hsp70-14A genes were located on the right arm of chromosome 2. The Hsp70 locus was considered to be an excellent marker for studying chromosomal evolution and relationships among A. darlingi populations. PMID:15098741

  12. Nonrandom chromosomal imbalances in primary mediastinal B-cell lymphoma detected by arbitrarily primed PCR fingerprinting.

    PubMed

    Scarpa, A; Taruscio, D; Scardoni, M; Iosi, F; Paradisi, S; Ennas, M G; Rigaud, G; Moore, P S; Menestrina, F

    1999-11-01

    We used arbitrarily primed polymerase chain reaction (AP-PCR) fingerprinting to identify chromosomal imbalances in six primary mediastinal B-cell lymphomas (PMBLs). Seventy-four chromosomal imbalances were detected, consisting of 49 sequence gains and 25 losses. Amplifications on chromosome X were seen in five cases, four of which involved the same chromosomal locus. Nonrandom gains at the same locus were also identified on chromosomes 2 and 7 in four cases and on chromosomes 5, 9, and 12 in three cases. Five PMBLs were also analyzed by comparative genomic hybridization (CGH), which found chromosome arm 9p amplification as the only nonrandom imbalance. Our data demonstrate that chromosomal amplifications outnumber losses in PMBL. These mainly involve chromosomes 9 and X and may reflect more complex phenomena, such as translocations or other chromosomal rearrangements, as AP-PCR found coexistent gains and losses on these chromosomes. Comparison between AP-PCR and CGH suggests that anomalies affecting the same chromosomal regions may occur at much higher frequencies than expected by CGH, suggesting that genomic amplifications are usually confined to DNA segments smaller than the megabase long segments required for detection in CGH. Modest increases in genetic material may be as effective as higher-level amplifications when affecting sites where a proto-oncogene resides.

  13. Cytogenetic Analysis of Segregation Distortion in Drosophila Melanogaster: The Cytological Organization of the Responder (Rsp) Locus

    PubMed Central

    Pimpinelli, S.; Dimitri, P.

    1989-01-01

    The segregation distortion phenomenon occurs in Drosophila melanogaster males carrying an SD second chromosome and an SD(+) homolog. In such males the SD chromosome is transmitted to the progeny more frequently than the expected 50% because of an abnormal differentiation of the SD(+)-bearing sperms. Three major loci are involved in this phenomenon: SD and Rsp, associated with the SD and SD(+) chromosome, respectively, and E(SD). In the present work we performed a cytogenetic analysis of the Rsp locus which was known to map to the centromeric heterochromatin of the second chromosome. Hoechst- and N-banding techniques were used to characterize chromosomes carrying Responder insensitive (Rsp(i)), Responder sensitive (Rsp(s)) and Responder supersensitive (Rsp(ss)) alleles. Our results locate the Rsp locus to the h39 region of 2R heterochromatin. This region is a Hoechstbright, N-banding negative heterochromatic block adjacent to the centromere. Quantitative variations of the h39 region were observed. The degree of sensitivity to Sd was found to be directly correlated with the physical size of that region, demonstrating that the Rsp locus is composed of repeated DNA. PMID:2470640

  14. Relationships between chromosome structure and chromosomal aberrations

    NASA Astrophysics Data System (ADS)

    Eidelman, Yuri; Andreev, Sergey

    An interphase nucleus of human lymphocyte was simulated by the novel Monte Carlo tech-nique. The main features of interphase chromosome structure and packaging were taken into account: different levels of chromatin organisation; nonrandom localisation of chromosomes within a nucleus; chromosome loci dynamics. All chromosomes in a nucleus were modelled as polymer globules. A dynamic pattern of intra/interchromosomal contacts was simulated. The detailed information about chromosomal contacts, such as distribution of intrachromoso-mal contacts over the length of each chromosome and dependence of contact probability on genomic separation between chromosome loci, were calculated and compared to the new exper-imental data obtained by the Hi-C technique. Types and frequencies of simple and complex radiation-induced chromosomal exchange aberrations (CA) induced by X-rays were predicted with taking formation and decay of chromosomal contacts into account. Distance dependence of exchange formation probability was calculated directly. mFISH data for human lymphocytes were analysed. The calculated frequencies of simple CA agreed with the experimental data. Complex CA were underestimated despite the dense packaging of chromosome territories within a nucleus. Possible influence of chromosome-nucleus structural organisation on the frequency and spectrum of radiation-induced chromosome aberrations is discussed.

  15. Differential activity of a tissue-specific extinguisher locus in hepatic and nonhepatic cells.

    PubMed Central

    Gourdeau, H; Peterson, T C; Fournier, R E

    1989-01-01

    Tissue-specific extinguisher 1 (Tse-1) is a genetic locus on mouse chromosome 11 that can repress expression of several liver genes in trans. This locus is clearly active in fibroblasts, as hepatoma cells retaining fibroblast chromosome 11 are extinguished for both tyrosine aminotransferase and phosphoenolpyruvate carboxykinase gene expression. To assess the activity of Tse-1 in other tissues, we transferred mouse chromosome 11 from several different cell types into rat hepatoma recipients. Tse-1 was active in nonhepatic cell lines derived from each primary germ layer, but Tse-1 activity was not apparent in hybrids between hepatoma cells and primary mouse hepatocytes. These differences in the genetic activity of murine Tse-1 were apparently heritable in cis. Images PMID:2568581

  16. Differential activity of a tissue-specific extinguisher locus in hepatic and nonhepatic cells.

    PubMed

    Gourdeau, H; Peterson, T C; Fournier, R E

    1989-05-01

    Tissue-specific extinguisher 1 (Tse-1) is a genetic locus on mouse chromosome 11 that can repress expression of several liver genes in trans. This locus is clearly active in fibroblasts, as hepatoma cells retaining fibroblast chromosome 11 are extinguished for both tyrosine aminotransferase and phosphoenolpyruvate carboxykinase gene expression. To assess the activity of Tse-1 in other tissues, we transferred mouse chromosome 11 from several different cell types into rat hepatoma recipients. Tse-1 was active in nonhepatic cell lines derived from each primary germ layer, but Tse-1 activity was not apparent in hybrids between hepatoma cells and primary mouse hepatocytes. These differences in the genetic activity of murine Tse-1 were apparently heritable in cis.

  17. Mapping of the Hor-3 locus encoding D hordein in Barley.

    PubMed

    Blake, T K; Ullrich, S E; Nilan, R A

    1982-12-01

    The hordein storage proteins of barley (Hordeum vulgare L.) are of intense interest due to their genetic diversity and prominence and impact on the industrial and agricultural uses of the seed. Two major hordein loci have been previously mapped on chromosome 5 (Hor-1 and Hor-2 encoding the C and B hordeins, respectively). A third major locus, Hor-3, which codes for D hordein, has been located in the centromeric region of chromosome 5, probably on the long arm. Two allelic variants with apparent molecular weights of 83,000 and 91,000 and similar isoelectric points of 8.0 comprise the products of this locus in the barley varieties 'Advance' and 'Triple Awned Lemma'. The D hordein examined is similar in molecular weight and isoelectric point to the high molecular weight (HMW) glutenin proteins encoded by the 1B chromosome of wheat (Triticum aestivum L.).

  18. A new HaeIII polymorphism at the D21S13 locus.

    PubMed

    Pulst, S M; Korenberg, J R; Ren, M; Greenwald, J

    1990-10-01

    DNA markers in the pericentromeric region of human chromosome 21 have shown linkage to a gene for Familial Alzheimer disease (FAD; St. George Hyslop et al. 1987). The limited informativeness of probes for the loci D21S13 and D21S16 have hindered precise mapping of the FAD locus and analysis of non-allelic heterogeneity in FAD (Schellenberg et al. 1988; St. George-Hyslop et al. 1987). We recently described a new EcoRII polymorphism at the D21S13 locus that was very informative in a large FAD pedigree (Pulst et al. 1990a,b). We now report another polymorphism for the D21S13 locus that further increases the informativeness of this locus.

  19. Molecular Mapping of the ROSY Locus in DROSOPHILA MELANOGASTER

    PubMed Central

    Coté, Babette; Bender, Welcome; Curtis, Daniel; Chovnick, Arthur

    1986-01-01

    The DNA from the chromosomal region of the Drosophila rosy locus has been examined in 83 rosy mutant strains. Several spontaneous and radiation-induced alleles were associated with insertions and deletions, respectively. The lesions are clustered in a 4-kb region. Some of the alleles identified on the DNA map have been located on the genetic map by fine-structure recombination experiments. The genetic and molecular maps are collinear, and the alignment identifies the DNA location of the rosy control region. A rosy RNA of 4.5 kb has been identified; its 5' end lies in or near the control region. PMID:2420682

  20. TaXA21-A1 on chromosome 5AL is associated with resistance to multiple pests in wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A quantitative trait locus QYr.osu-5A on the long arm of chromosome 5A in bread wheat (Triticum aestivum L., 2n=6x=42; AABBDD) was previously reported to confer consistent resistance in adult plants to predominant stripe rust races, but the gene causing the quantitative trait locus (QTL) is not know...

  1. Phenotypic and fine genetic characterization of the D locus controlling fruit acidity in peach

    PubMed Central

    2009-01-01

    Background Acidity is an essential component of the organoleptic quality of fleshy fruits. However, in these fruits, the physiological and molecular mechanisms that control fruit acidity remain unclear. In peach the D locus controls fruit acidity; low-acidity is determined by the dominant allele. Using a peach progeny of 208 F2 trees, the D locus was mapped to the proximal end of linkage group 5 and co-localized with major QTLs involved in the control of fruit pH, titratable acidity and organic acid concentration and small QTLs for sugar concentration. To investigate the molecular basis of fruit acidity in peach we initiated the map-based cloning of the D locus. Results In order to generate a high-resolution linkage map in the vicinity of the D locus, 1,024 AFLP primer combinations were screened using DNA of bulked acid and low-acid segregants. We also screened a segregating population of 1,718 individuals for chromosomal recombination events linked to the D locus and identified 308 individuals with recombination events close to D. Using these recombinant individuals we delimited the D locus to a genetic interval of 0.4 cM. We also constructed a peach BAC library of 52,000 clones with a mean insert size of 90 kb. The screening of the BAC library with markers tightly linked to D locus indicated that 1 cM corresponds to 250 kb at the vicinity of the D locus. Conclusion In the present work we presented the first high-resolution genetic map of D locus in peach. We also constructed a peach BAC library of approximately 15× genome equivalent. This fine genetic and physical characterization of the D locus is the first step towards the isolation of the gene(s) underlying fruit acidity in peach. PMID:19445673

  2. Genetic mapping of a locus predisposing to human colorectal cancer

    SciTech Connect

    Peltomaeki, P.; Aaltonen, L.A.; Pylkkaenen, L.; Chappelle, A. de la ); Sistonen, P. Finnish Red Cross Blood Transfusion Service, Helsinki ); Mecklin, J.P. ); Haervinen, H. ); Green, J.S. ); Jass, J.R. ); Weber, J.L. ); Leach, F.S.; Petersen, G.M.; Hamilton, S.R.; Vogelstein, B. Johns Hopkins Hospital, Baltimore, MD )

    1993-05-07

    Genetic linkage analysis was used to determine whether a specific chromosomal locus could be implicated in families with a history of early onset cancer but with no other unique features. Close linkage of disease to anonymous microsatellite markers on chromosome 2 was demonstrated in two large kindreds. The pairwise lod scores for linkage to marker D2S123 in these kindreds were 6.39 and 1.45 at zero recombination, and multipoint linkage with flanking markers resulted in lod scores of 6.47 and 6.01. These results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease. 13 refs., 1 fig., 1 tab.

  3. Prenatal Diagnosis of a Fetus with Congenital Heart Defect and Ring Chromosome 14

    PubMed Central

    Sánchez, Javier; García-Díaz, Lutgardo; Chinchón, David; Antiñolo, Guillermo

    2012-01-01

    Monosomy of chromosome 14 has been reported in only a few prenatal cases. Generally, this monosomy is associated with a mosaicism of ring chromosome 14. Ring chromosome 14 is a rare cytogenetic entity with clinical characteristics that include growth retardation, facial dysmorphia, hypotonia, seizures, and retinitis pigmentosa. Given that the majority of symptoms appear postnatally, few cases have been reported of prenatal diagnosis of mosaicism monosomy/ring chromosome 14. We describe the prenatal diagnosis of a case of chromosomal mosaicism, a cell line with ring chromosome 14, r(14), and a second cell line with monosomy 14, in a fetus with aortic coarctation and chamber asymmetry. This is the first case of a prenatal diagnosis associating mosaicism with ring chromosome 14, monosomy 14, and fetal cardiopathy. We identified the exact breakpoint in ring chromosome 14 in IGH locus, which may provide further insight into the mode of ring formation as well as prenatal findings. PMID:23198189

  4. Human chromosome 8.

    PubMed Central

    Wood, S

    1988-01-01

    The role of human chromosome 8 in genetic disease together with the current status of the genetic linkage map for this chromosome is reviewed. Both hereditary genetic disease attributed to mutant alleles at gene loci on chromosome 8 and neoplastic disease owing to somatic mutation, particularly chromosomal translocations, are discussed. PMID:3070042

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

    SciTech Connect

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

    1986-03-01

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

  6. Candidate regions for Waardenburg syndrome type II: Search for a second WS locus

    SciTech Connect

    Nance, W.E.; Pandya, A.; Blanton, S.H.

    1994-09-01

    Waardenburg syndrome is an autosomal dominant disorder characterized by deafness and pigmentary abnormalities such as heterochromia of irides, hypopigmented skin patches, white forlock and premature graying. Clinically the syndrome has been classified into three types. Type II differs from type I in that dystopia canthorum is generally absent, and type III has associated limb anomalies. Recently linkage analysis localized the gene for WSI to chromosome 2q. PAX-3, which is a human analogue of the murine pax-3 locus, maps to this region and mutations in this gene have been found to segregate with WSI. However genetic heterogeneity clearly exists: most if not all WSII families are unlinked to PAX-3 while most if not all WSI cases are linked. We ascertained a four-year-old female child with an interstitial deletion of chromosome 13 who had features of WS including bilateral congenital sensorineural hearing loss, pale blue irides and pinched nostrils as well as hypertelorism microcephaly, bilateral eyelid ptosis, digitalization of thumbs and fifth finger clinodactyly. High resolution chromosomal analysis revealed a de novo interstitial deletion of 13q22-33.2. There was no family history of WS or retardation. A similar deletion in the region of 13q21-32 has been described in a 13-year-old boy with features of WSII. These two cases strongly suggested that this chromosomal region may include a second locus for WS. We have identified eight families with clinical features of WS type I which have been excluded from linkage to the PAX-3 locus. We have typed these families for microsatellite markers spanning chromosome 13. Linkage between WSII and the chromosome 13 markers was excluded in these families. Hirschsprung disease has been associated with WS and it has recently been mapped to chromosome 10q11.2-q21.1. We are currently typing the 8 families for microsatellites in this region.

  7. Sequence Variation Within the Fragile X Locus

    PubMed Central

    Mathews, Debra J.; Kashuk, Carl; Brightwell, Gale; Eichler, Evan E.; Chakravarti, Aravinda

    2001-01-01

    The human genome provides a reference sequence, which is a template for resequencing studies that aim to discover and interpret the record of common ancestry that exists in extant genomes. To understand the nature and pattern of variation and linkage disequilibrium comprising this history, we present a study of ∼31 kb spanning an ∼70 kb region of FMR1, sequenced in a sample of 20 humans (worldwide sample) and four great apes (chimp, bonobo, and gorilla). Twenty-five polymorphic sites and two insertion/deletions, distributed in 11 unique haplotypes, were identified among humans. Africans are the only geographic group that do not share any haplotypes with other groups. Parsimony analysis reveals two main clades and suggests that the four major human geographic groups are distributed throughout the phylogenetic tree and within each major clade. An African sample appears to be most closely related to the common ancestor shared with the three other geographic groups. Nucleotide diversity, π, for this sample is 2.63 ± 6.28 × 10−4. The mutation rate, μ, is 6.48 × 10−10 per base pair per year, giving an ancestral population size of ∼6200 and a time to the most recent common ancestor of ∼320,000 ± 72,000 per base pair per year. Linkage disequilibrium (LD) at the FMR1 locus, evaluated by conventional LD analysis and by the length of segment shared between any two chromosomes, is extensive across the region. PMID:11483579

  8. Construction, complete sequence, and annotation of a BAC contig covering the silkworm chorion locus

    PubMed Central

    Chen, Zhiwei; Nohata, Junko; Guo, Huizhen; Li, Shenglong; Liu, Jianqiu; Guo, Youbing; Yamamoto, Kimiko; Kadono-Okuda, Keiko; Liu, Chun; Arunkumar, Kallare P.; Nagaraju, Javaregowda; Zhang, Yan; Liu, Shiping; Labropoulou, Vassiliki; Swevers, Luc; Tsitoura, Panagiota; Iatrou, Kostas; Gopinathan, Karumathil P.; Goldsmith, Marian R.; Xia, Qingyou; Mita, Kazuei

    2015-01-01

    The silkmoth chorion was studied extensively by F.C. Kafatos’ group for almost 40 years. However, the complete structure of the chorion locus was not obtained in the genome sequence of Bombyx mori published in 2008 due to repetitive sequences, resulting in gaps and an incomplete view of the locus. To obtain the complete sequence of the chorion locus, expressed sequence tags (ESTs) derived from follicular epithelium cells were used as probes to screen a bacterial artificial chromosome (BAC) library. Seven BACs were selected to construct a contig which covered the whole chorion locus. By Sanger sequencing, we successfully obtained complete sequences of the chorion locus spanning 871,711 base pairs on chromosome 2, where we annotated 127 chorion genes. The dataset reported here will recruit more researchers to revisit one of the oldest model systems which has been used to study developmentally regulated gene expression. It also provides insights into egg development and fertilization mechanisms and is relevant to applications related to improvements in breeding procedures and transgenesis. PMID:26594380

  9. Construction, complete sequence, and annotation of a BAC contig covering the silkworm chorion locus.

    PubMed

    Chen, Zhiwei; Nohata, Junko; Guo, Huizhen; Li, Shenglong; Liu, Jianqiu; Guo, Youbing; Yamamoto, Kimiko; Kadono-Okuda, Keiko; Liu, Chun; Arunkumar, Kallare P; Nagaraju, Javaregowda; Zhang, Yan; Liu, Shiping; Labropoulou, Vassiliki; Swevers, Luc; Tsitoura, Panagiota; Iatrou, Kostas; Gopinathan, Karumathil P; Goldsmith, Marian R; Xia, Qingyou; Mita, Kazuei

    2015-01-01

    The silkmoth chorion was studied extensively by F.C. Kafatos' group for almost 40 years. However, the complete structure of the chorion locus was not obtained in the genome sequence of Bombyx mori published in 2008 due to repetitive sequences, resulting in gaps and an incomplete view of the locus. To obtain the complete sequence of the chorion locus, expressed sequence tags (ESTs) derived from follicular epithelium cells were used as probes to screen a bacterial artificial chromosome (BAC) library. Seven BACs were selected to construct a contig which covered the whole chorion locus. By Sanger sequencing, we successfully obtained complete sequences of the chorion locus spanning 871,711 base pairs on chromosome 2, where we annotated 127 chorion genes. The dataset reported here will recruit more researchers to revisit one of the oldest model systems which has been used to study developmentally regulated gene expression. It also provides insights into egg development and fertilization mechanisms and is relevant to applications related to improvements in breeding procedures and transgenesis. PMID:26594380

  10. Meiotic drive influences the outcome of sexually antagonistic selection at a linked locus.

    PubMed

    Patten, M M

    2014-11-01

    Most meiotic drivers, such as the t-haplotype in Mus and the segregation distorter (SD) in Drosophila, act in a sex-specific manner, gaining a transmission advantage through one sex although suffering only the fitness costs associated with the driver in the other. Their inheritance is thus more likely through one of the two sexes, a property they share with sexually antagonistic alleles. Previous theory has shown that pairs of linked loci segregating for sexually antagonistic alleles are more likely to remain polymorphic and that linkage disequilibrium accrues between them. I probe this similarity between drive and sexual antagonism and examine the evolution of chromosomes experiencing these selection pressures simultaneously. Reminiscent of previous theory, I find that: the opportunity for polymorphism increases for a sexually antagonistic locus that is physically linked to a driving locus; the opportunity for polymorphism at a driving locus also increases when linked to a sexually antagonistic locus; and stable linkage disequilibrium accompanies any polymorphic equilibrium. Additionally, I find that drive at a linked locus favours the fixation of sexually antagonistic alleles that benefit the sex in which drive occurs. Further, I show that under certain conditions reduced recombination between these two loci is selectively favoured. These theoretical results provide clear, testable predictions about the nature of sexually antagonistic variation on driving chromosomes and have implications for the evolution of genomic architecture.

  11. Confirmation of Single-Locus Sex Determination and Female Heterogamety in Willow Based on Linkage Analysis

    PubMed Central

    Fang, Lecheng; Li, Xiaoping; Yin, Tongming

    2016-01-01

    In this study, we constructed high-density genetic maps of Salix suchowensis and mapped the gender locus with an F1 pedigree. Genetic maps were separately constructed for the maternal and paternal parents by using amplified fragment length polymorphism (AFLP) markers and the pseudo-testcross strategy. The maternal map consisted of 20 linkage groups that spanned a genetic distance of 2333.3 cM; whereas the paternal map contained 21 linkage groups that covered 2260 cM. Based on the established genetic maps, it was found that the gender of willow was determined by a single locus on linkage group LG_03, and the female was the heterogametic gender. Aligned with mapped SSR markers, linkage group LG_03 was found to be associated with chromosome XV in willow. It is noteworthy that marker density in the vicinity of the gender locus was significantly higher than that expected by chance alone, which indicates severe recombination suppression around the gender locus. In conclusion, this study confirmed the findings on the single-locus sex determination and female heterogamety in willow. It also provided additional evidence that validated the previous studies, which found that different autosomes evolved into sex chromosomes between the sister genera of Salix (willow) and Populus (poplar). PMID:26828940

  12. New insight into the man-mouse comparative map of the X chromosome

    SciTech Connect

    Blair, H.J.; Reed, V.; Laval, S.H.; Boyd, Y. )

    1994-01-15

    Two conserved loci, DXHX674h and DXHX679h, which map to Xp11.22-Xp11.21 on the human X chromosome short arm, have been positioned between the loci for proteolipid protein (Plp) and the Ela subunit of pyruvate dehydrogenase (Pdha1) in the distal region of the mouse X chromosome using Mus musculus x Mus spretus interspecific backcrosses. These data, together with previous comparative mapping studies on another conserved locus (DXF34) and the locus that encodes the erythroid transcription factor (GATA1), reveal that loci that map to the proximal region of the human X chromosome short arm lie in four different regions of the mouse X chromosome and that the human and mouse X chromosomes contain a minimum of eight conserved segments. 28 refs., 4 figs.

  13. Sex Determination in the Fly Megaselia Scalaris, a Model System for Primary Steps of Sex Chromosome Evolution

    PubMed Central

    Traut, W.

    1994-01-01

    The fly Megaselia scalaris Loew possesses three homomorphic chromosome pairs; 2 is the sex chromosome pair in two wild-type laboratory stocks of different geographic origin (designated ``original'' sex chromosome pair in this paper). The primary male-determining function moves at a very low rate to other chromosomes, thereby creating new Y chromosomes. Random amplified polymorphic DNA markers obtained by polymerase chain reaction with single decamer primers and a few available phenotypic markers were used in testcrosses to localize the sex-determining loci and to define the new sex chromosomes. Four cases are presented in which the primary male-determining function had been transferred from the original Y chromosome to a new locus either on one of the autosomes or on the original X chromosome, presumably by transposition. In these cases, the sex-determining function had moved to a different locus without an obvious cotransfer of other Y chromosome markers. Thus, with Megaselia we are afforded an experimental system to study the otherwise hypothetical primary stages of sex chromosome evolution. An initial molecular differentiation is apparent even in the new sex chromosomes. Molecular differences between the original X and Y chromosomes illustrate a slightly more advanced stage of sex chromosome evolution. PMID:8005417

  14. Undetected sex chromosome aneuploidy by chromosomal microarray.

    PubMed

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

    2012-11-01

    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  15. Integrative bacterial artificial chromosomes for DNA integration into the Bacillus subtilis chromosome.

    PubMed

    Juhas, Mario; Ajioka, James W

    2016-06-01

    Bacillus subtilis is a well-characterized model bacterium frequently used for a number of biotechnology and synthetic biology applications. Novel strategies combining the advantages of B. subtilis with the DNA assembly and editing tools of Escherichia coli are crucial for B. subtilis engineering efforts. We combined Gibson Assembly and λ red recombineering in E. coli with RecA-mediated homologous recombination in B. subtilis for bacterial artificial chromosome-mediated DNA integration into the well-characterized amyE target locus of the B. subtilis chromosome. The engineered integrative bacterial artificial chromosome iBAC(cav) can accept any DNA fragment for integration into B. subtilis chromosome and allows rapid selection of transformants by B. subtilis-specific antibiotic resistance and the yellow fluorescent protein (mVenus) expression. We used the developed iBAC(cav)-mediated system to integrate 10kb DNA fragment from E. coli K12 MG1655 into B. subtilis chromosome. iBAC(cav)-mediated chromosomal integration approach will facilitate rational design of synthetic biology applications in B. subtilis.

  16. Locus of control and obesity.

    PubMed

    Neymotin, Florence; Nemzer, Louis R

    2014-01-01

    In the developed world, the hazards associated with obesity have largely outstripped the risk of starvation. Obesity remains a difficult public health issue to address, due in large part to the many disciplines involved. A full understanding requires knowledge in the fields of genetics, endocrinology, psychology, sociology, economics, and public policy - among others. In this short review, which serves as an introduction to the Frontiers in Endocrinology research topic, we address one cross-disciplinary relationship: the interaction between the hunger/satiation neural circuitry, an individual's perceived locus of control, and the risk for obesity. Mammals have evolved a complex system for modulating energy intake. Overlaid on this, in humans, there exists a wide variation in "perceived locus of control" - that is, the extent to which an individual believes to be in charge of the events that affect them. Whether one has primarily an internal or external locus of control itself affects, and is affected by, external and physiological factors and has been correlated with the risk for obesity. Thus, the path from hunger and satiation to an individual's actual behavior may often be moderated by psychological factors, included among which is locus of control. PMID:25339940

  17. A nonclassical MHC class I U lineage locus in zebrafish with a null haplotypic variant

    PubMed Central

    Dirscherl, Hayley; Yoder, Jeffrey A.

    2015-01-01

    Three sequence lineages of MHC class I genes have been described in zebrafish (Danio rerio): U, Z, and L. The U lineage genes encoded on zebrafish chromosome 19 are predicted to provide the classical function of antigen presentation. This MHC class I locus displays significant haplotypic variation and is the only MHC class I locus in zebrafish that shares conserved synteny with the core mammalian MHC. Here we describe two MHC class I U lineage genes, mhc1ula and mhc1uma, that map to chromosome 22. Unlike the U lineage proteins encoded on chromosome 19, Ula and Uma likely play a nonclassical role as they lack conservation of key peptide binding residues, display limited polymorphic variation, and exhibit tissue-specific expression. We also describe a null haplotype at this chromosome 22 locus in which the mhc1ula and mhc1uma genes are absent due to a ∼30 kb deletion with no other MHC class I sequences present. Functional and non-functional transcripts of mhc1ula and mhc1uma were identified; however, mhc1uma transcripts were often not amplified or amplified at low levels from individuals possessing an apparently bona fide gene. These distinct U lineage genes may be restricted to the superorder Ostariophysi as similar sequences only could be identified from the blind cavefish (Astyanyx mexicanus), fathead minnow (Pimephales promelas), goldfish (Carassius auratus), and grass carp (Ctenopharyngodon idellus). PMID:26254596

  18. A nonclassical MHC class I U lineage locus in zebrafish with a null haplotypic variant.

    PubMed

    Dirscherl, Hayley; Yoder, Jeffrey A

    2015-09-01

    Three sequence lineages of MHC class I genes have been described in zebrafish (Danio rerio): U, Z, and L. The U lineage genes encoded on zebrafish chromosome 19 are predicted to provide the classical function of antigen presentation. This MHC class I locus displays significant haplotypic variation and is the only MHC class I locus in zebrafish that shares conserved synteny with the core mammalian MHC. Here, we describe two MHC class I U lineage genes, mhc1ula and mhc1uma, that map to chromosome 22. Unlike the U lineage proteins encoded on chromosome 19, Ula and Uma likely play a nonclassical role as they lack conservation of key peptide binding residues, display limited polymorphic variation, and exhibit tissue-specific expression. We also describe a null haplotype at this chromosome 22 locus in which the mhc1ula and mhc1uma genes are absent due to a ~30 kb deletion with no other MHC class I sequences present. Functional and non-functional transcripts of mhc1ula and mhc1uma were identified; however, mhc1uma transcripts were often not amplified or amplified at low levels from individuals possessing an apparently bona fide gene. These distinct U lineage genes may be restricted to the superorder Ostariophysi as similar sequences only could be identified from the blind cavefish (Astyanax mexicanus), fathead minnow (Pimephales promelas), goldfish (Carassius auratus), and grass carp (Ctenopharyngodon idella). PMID:26254596

  19. The precarious prokaryotic chromosome.

    PubMed

    Kuzminov, Andrei

    2014-05-01

    Evolutionary selection for optimal genome preservation, replication, and expression should yield similar chromosome organizations in any type of cells. And yet, the chromosome organization is surprisingly different between eukaryotes and prokaryotes. The nuclear versus cytoplasmic accommodation of genetic material accounts for the distinct eukaryotic and prokaryotic modes of genome evolution, but it falls short of explaining the differences in the chromosome organization. I propose that the two distinct ways to organize chromosomes are driven by the differences between the global-consecutive chromosome cycle of eukaryotes and the local-concurrent chromosome cycle of prokaryotes. Specifically, progressive chromosome segregation in prokaryotes demands a single duplicon per chromosome, while other "precarious" features of the prokaryotic chromosomes can be viewed as compensations for this severe restriction.

  20. B-chromosome evolution.

    PubMed Central

    Camacho, J P; Sharbel, T F; Beukeboom, L W

    2000-01-01

    B chromosomes are extra chromosomes to the standard complement that occur in many organisms. They can originate in a number of ways including derivation from autosomes and sex chromosomes in intra- and interspecies crosses. Their subsequent molecular evolution resembles that of univalent sex chromosomes, which involves gene silencing, heterochromatinization and the accumulation of repetitive DNA and transposons. B-chromosome frequencies in populations result from a balance between their transmission rates and their effects on host fitness. Their long-term evolution is considered to be the outcome of selection on the host genome to eliminate B chromosomes or suppress their effects and on the B chromosome's ability to escape through the generation of new variants. Because B chromosomes interact with the standard chromosomes, they can play an important role in genome evolution and may be useful for studying molecular evolutionary processes. PMID:10724453

  1. Updated listing of haplotypes at the human phenylalanine hydroxylase (PAH) locus

    SciTech Connect

    Eisensmith, R.C.; Woo, S.L.C. )

    1992-12-01

    Analysis of mutant PAH chromosomes has identified approximately 60 different single-base substitutions and deletions within the PAH locus. Nearly all of these molecular lesions are in strong linkage disequilibrium with specific RFLP haplotypes in different ethnic populations. Thus, haplotype analysis is not only useful for diagnostic purposes but is proving to be a valuable tool in population genetic studies of the origin and spread of phenylketonuria alleles in human populations. PCR-based methods have been developed to detect six of the eight polymorphic restriction sites used for determination of RFLP haplotypes at the PAH locus. A table of the proposed expanded haplotypes is given.

  2. Pigment-cell-specific genes from fibroblasts are transactivated after chromosomal transfer into melanoma cells.

    PubMed Central

    Powers, T P; Shows, T B; Davidson, R L

    1994-01-01

    Human and mouse fibroblast chromosomes carrying tyrosinase or b-locus genes were introduced, by microcell hybridization, into pigmented Syrian hamster melanoma cells, and the microcell hybrids were tested for transactivation of the fibroblast tyrosinase and b-locus genes. By using species-specific PCR amplification to distinguish fibroblast and melanoma cDNAs, it was demonstrated that the previously silent fibroblast tyrosinase and b-locus genes were transactivated following chromosomal transfer into pigmented melanoma cells. However, transactivation of the mouse fibroblast tyrosinase gene was unstable in microcell hybrid subclones and possibly dependent on a second fibroblast locus that could have segregated in the subclones. This second locus was not necessary for transactivation of the fibroblast b-locus gene, thus demonstrating noncoordinate transactivation of fibroblast tyrosinase and b-locus genes. Transactivation of the fibroblast tyrosinase gene in microcell hybrids apparently is dependent on the absence of a putative fibroblast extinguisher locus for tyrosinase gene expression, which presumably is responsible for the extinction of pigmentation in hybrids between karyotypically complete fibroblasts and melanoma cells. Images PMID:8289799

  3. Pigment-cell-specific genes from fibroblasts are transactivated after chromosomal transfer into melanoma cells

    SciTech Connect

    Powers, T.P.; Davidson, R.L.; Shows, T.B.

    1994-02-01

    Human and mouse fibroblast chromosomes carrying tyrosinase or b-locus genes were introduced, by microcell hybridization, into pigmented Syrian hamster melanoma cells, and the microcell hybrids were tested for transactivation of the fibroblast tyrosinase and b-locus genes. By using species-specific PCR amplification to distinguish fibroblast and melanoma cDNAs, it was demonstrated that the previously silent fibroblast tyrosinase and b-locus genes were transactivated following chromosomal transfer into pigmented melanoma cells. However, transactivation of the mouse fibroblast tyrosinase gene was unstable in microcell hybrid subclones and possibly dependent on a second fibroblast locus that could have segregated in the subclones. This second locus was not necessary for transactivation of the fibroblast b-locus gene, thus demonstrating noncoordinate transactivation of fibroblast tyrosinase and b-locus genes. Transactivation of the fibroblast tyrosinase gene in microcell hybrids apparently is dependent on the absence of a putative fibroblast extinguisher locus for tyrosinase gene expression, which presumably is responsible for the extinction of pigmentation in hybrids between karyotypically complete fibroblasts and melanoma cells. 46 refs., 5 figs., 2 tabs.

  4. Locus of Control and Status Attainment.

    ERIC Educational Resources Information Center

    Bensman, Miriam Roza; Haller, Archibald O.

    Utilizing data derived from 277 rural, male respondents initially enrolled in Lenawee County, Michigan high schools, the Rotter's Internal-External Locus of Control Scale was employed to test the hypothesis that locus of control will have interactive rather than additive effects on the process of status attainment. Locus of control was defined as…

  5. The gamma fibrinogen gene (FGG) maps to chromosome 17 in both cattle and sheep.

    PubMed

    Johnson, S E; Barendse, W; Hetzel, D J

    1993-01-01

    The gamma fibrinogen gene (FGG) was localised in both cattle and sheep using in situ hybridisation. The probe employed was a 1-kb bovine cDNA fragment. Based on observations of QFQ-banded chromosome preparations, this locus is on bovine chromosome 17q12-->q13 and on the homologous sheep chromosome 17. This localisation is, to our knowledge, the first assignment to chromosome 17 in either the bovine or ovine genome. In addition to localising FGG to this chromosome, the assignment provisionally maps the previously unassigned syntenic group U23, containing (besides FGG) the genes for mitochondrial aldehyde dehydrogenase 2 (ALDH2), interleukin 2 (IL2), immunoglobulin lambda (IGL), and beta fibrinogen (FGB), to chromosome 17 in cattle and probably to the same chromosome in sheep.

  6. Transposable elements as catalysts for chromosome rearrangements.

    PubMed

    Zhang, Jianbo; Yu, Chuanhe; Krishnaswamy, Lakshminarasimhan; Peterson, Thomas

    2011-01-01

    Barbara McClintock first showed that transposable elements in maize can induce major chromosomal rearrangements, including duplications, deletions, inversions, and translocations. More recently, researchers have made significant progress in elucidating the mechanisms by which transposons can induce genome rearrangements. For the Ac/Ds transposable element system, rearrangements are generated when the termini of different elements are used as substrates for transposition. The resulting alternative transposition reaction directly generates a variety of rearrangements. The size and type of rearrangements produced depend on the location and orientation of transposon insertion. A single locus containing a pair of alternative transposition-competent elements can produce a virtually unlimited number of genome rearrangements. With a basic understanding of the mechanisms involved, researchers are beginning to utilize both naturally occurring and in vitro-generated configurations of transposable elements in order to manipulate chromosome structure. PMID:21181539

  7. Transposable elements as catalysts for chromosome rearrangements.

    PubMed

    Zhang, Jianbo; Yu, Chuanhe; Krishnaswamy, Lakshminarasimhan; Peterson, Thomas

    2011-01-01

    Barbara McClintock first showed that transposable elements in maize can induce major chromosomal rearrangements, including duplications, deletions, inversions, and translocations. More recently, researchers have made significant progress in elucidating the mechanisms by which transposons can induce genome rearrangements. For the Ac/Ds transposable element system, rearrangements are generated when the termini of different elements are used as substrates for transposition. The resulting alternative transposition reaction directly generates a variety of rearrangements. The size and type of rearrangements produced depend on the location and orientation of transposon insertion. A single locus containing a pair of alternative transposition-competent elements can produce a virtually unlimited number of genome rearrangements. With a basic understanding of the mechanisms involved, researchers are beginning to utilize both naturally occurring and in vitro-generated configurations of transposable elements in order to manipulate chromosome structure.

  8. Chromosome Disorder Outreach

    MedlinePlus

    ... BLOG Join Us Donate You are not alone. Chromosome Disorder Outreach, Inc. is a non-profit organization, ... Support For all those diagnosed with any rare chromosome disorder. Since 1992, CDO has supported the parents ...

  9. Global reorganization of budding yeast chromosome conformation in different physiological conditions

    PubMed Central

    Tjong, Harianto; Weider, Elodie; Herzog, Mareike; Young, Barry; Brune, Christiane; Müllner, Daniel; Loewen, Christopher; Alber, Frank; Weis, Karsten

    2016-01-01

    The organization of the genome is nonrandom and important for correct function. Specifically, the nuclear envelope plays a critical role in gene regulation. It generally constitutes a repressive environment, but several genes, including the GAL locus in budding yeast, are recruited to the nuclear periphery on activation. Here, we combine imaging and computational modeling to ask how the association of a single gene locus with the nuclear envelope influences the surrounding chromosome architecture. Systematic analysis of an entire yeast chromosome establishes that peripheral recruitment of the GAL locus is part of a large-scale rearrangement that shifts many chromosomal regions closer to the nuclear envelope. This process is likely caused by the presence of several independent anchoring points. To identify novel factors required for peripheral anchoring, we performed a genome-wide screen and demonstrated that the histone acetyltransferase SAGA and the activity of histone deacetylases are needed for this extensive gene recruitment to the nuclear periphery. PMID:26811423

  10. Meiotic drive of chromosomal knobs reshaped the maize genome.

    PubMed Central

    Buckler, E S; Phelps-Durr, T L; Buckler, C S; Dawe, R K; Doebley, J F; Holtsford, T P

    1999-01-01

    Meiotic drive is the subversion of meiosis so that particular genes are preferentially transmitted to the progeny. Meiotic drive generally causes the preferential segregation of small regions of the genome; however, in maize we propose that meiotic drive is responsible for the evolution of large repetitive DNA arrays on all chromosomes. A maize meiotic drive locus found on an uncommon form of chromosome 10 [abnormal 10 (Ab10)] may be largely responsible for the evolution of heterochromatic chromosomal knobs, which can confer meiotic drive potential to every maize chromosome. Simulations were used to illustrate the dynamics of this meiotic drive model and suggest knobs might be deleterious in the absence of Ab10. Chromosomal knob data from maize's wild relatives (Zea mays ssp. parviglumis and mexicana) and phylogenetic comparisons demonstrated that the evolution of knob size, frequency, and chromosomal position agreed with the meiotic drive hypothesis. Knob chromosomal position was incompatible with the hypothesis that knob repetitive DNA is neutral or slightly deleterious to the genome. We also show that environmental factors and transposition may play a role in the evolution of knobs. Because knobs occur at multiple locations on all maize chromosomes, the combined effects of meiotic drive and genetic linkage may have reshaped genetic diversity throughout the maize genome in response to the presence of Ab10. Meiotic drive may be a major force of genome evolution, allowing revolutionary changes in genome structure and diversity over short evolutionary periods. PMID:10471723

  11. 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.

  12. Chromosomal localization of TIL, a gene encoding a protein related to the Drosophila transmembrane receptor Toll, to human chromosome 4p14

    SciTech Connect

    Taguchi, Takahiro; Testa, J.R.; Mitcham, J.L.; Dower, S.K.; Sims, J.E.

    1996-03-05

    This report describes the localization of the the TIL gene to human chromosome 4p14 using fluorescence in situ hybridization. This gene encodes a protein which is related to the Drosophila transmembrane receptor Toll and the mammalian interleukin-1 receptor, which share similarities in structure and function. The Drosophila gene is also important during embryonic development, which makes TIL a candidate locus for human congenital malformations that are genetically linked to human chromosome 4. 17 refs., 1 fig.

  13. Polymorphic DNA haplotypes at the phenylalanine hydroxylase (PAH) locus in European families with phenylketonuria (PKU).

    PubMed

    Daiger, S P; Chakraborty, R; Reed, L; Fekete, G; Schuler, D; Berenssi, G; Nasz, I; Brdicka, R; Kamarýt, J; Pijácková, A

    1989-08-01

    DNA haplotype data from the phenylalanine hydroxylase (PAH) locus are available from a number of European populations as a result of RFLP testing for genetic counseling in families with phenylketonuria (PKU). We have analyzed data from Hungary and Czechoslovakia together with published data from five additional countries--Denmark, Switzerland, Scotland, Germany, and France--representing a broad geographic and ethnographic range. The data include 686 complete chromosomal haplotypes for eight RFLP sites assayed in 202 unrelated Caucasian families with PKU. Forty-six distinct RFLP haplotypes have been observed to date, 10 unique to PKU-bearing chromosomes, 12 unique to non-PKU chromosomes, and the remainder found in association with both types. Despite the large number of haplotypes observed (still much less than the theoretical maximum of 384), five haplotypes alone account for more than 76% of normal European chromosomes and four haplotypes alone account for more than 80% of PKU-bearing chromosomes. We evaluated the distribution of haplotypes and alleles within these populations and calculated pairwise disequilibrium values between RFLP sites and between these sites and a hypothetical PKU "locus." These are statistically significant differences between European populations in the frequencies of non-PKU chromosomal haplotypes (P = .025) and PKU chromosomal haplotypes (P much less than .001). Haplotype frequencies of the PKU and non-PKU chromosomes also differ significantly (P much less than .001. Disequilibrium values are consistent with the PAH physical map and support the molecular evidence for multiple, independent PKU mutations in Caucasians. However, the data do not support a single geographic origin for these mutations.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Bloom syndrome and maternal uniparental disomy for chromosome 15

    SciTech Connect

    Woodage, T.; Prasad, M.; Trent, R.J.; Smith, A. ); Dixon, J.W.; Romain, D.R.; Columbano-Green, L.M.; Selby, R.E. ); Graham, D. ); Rogan, P.K. )

    1994-07-01

    Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions. 37 refs., 3 figs., 2 tabs.

  15. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  16. Identification of the modifier locus that suppresses neonatal lethality in (♀DDD × ♂DH- Dh/+) F₁-Dh/+ male mice.

    PubMed

    Suto, Jun-ichi

    2011-10-01

    Most F(1)-Dh/+ male mice resulting from a cross between inbred DDD strain females and DH-Dh/+ strain males exhibit growth retardation and die during the neonatal period. The lethality is caused by a combination of three independent gene loci, namely the Dh locus on chromosome 1, Grdhq1 locus on the X chromosome, and a putative Y chromosome-linked locus in some strains. Among these loci, Grdhq1 was previously mapped to a distal region of the X chromosome using progeny from♀(♀DDD × ♂DH-+/+) F(1) × ♂DH-Dh/+ mice. In this study, fine mapping of Grdhq1 was performed using progeny of ♀(♀DDD × ♂CAST/EiJ) F(1) ♂DH-Dh/+ mice. Contrary to expectation, Dh/+ male pups carrying the DDD allele at DXMit135 (genetic marker nearest to Grdhq1) survived to weaning. The presence of modifier loci that suppressed the lethality by impeding the action of Grdhq1 was suggested; therefore, a genome-wide scan was performed in the surviving Dh/+ males. As a result, a significant modifier locus was identified on proximal chromosome 11. This in turn suggested that Grdhq1 was located more distally than we had expected; that is, the actual location of Grdhq1 appeared to be near and/or distal to the Mid1 locus. Thus, the results revealed that the neonatal lethality in (DDD × DH-Dh/+) F(1)-Dh/+ males was caused by the fourth gene locus on chromosome 11 in addition to the above-mentioned three gene loci on chromosomes 1, X, and Y.

  17. Chromosomal Disorders and Autism.

    ERIC Educational Resources Information Center

    Gillberg, Christopher

    1998-01-01

    This paper reviews the literature on chromosomal aberrations in autism, especially possible gene markers. It notes that Chromosome 15 and numerical and structural abnormalities of the sex chromosomes have been most frequently reported as related to the genesis of autism. (Author/DB)

  18. Single locus sex determination and female heterogamety in the basket willow (Salix viminalis L.).

    PubMed

    Pucholt, P; Rönnberg-Wästljung, A-C; Berlin, S

    2015-06-01

    Most eukaryotes reproduce sexually and a wealth of different sex determination mechanisms have evolved in this lineage. Dioecy or separate sexes are rare among flowering plants but have repeatedly evolved from hermaphroditic ancestors possibly involving male or female sterility mutations. Willows (Salix spp.) and poplars (Populus spp.) are predominantly dioecious and are members of the Salicaceae family. All studied poplars have sex determination loci on chromosome XIX, however, the position differs among species and both male and female heterogametic system exists. In contrast to the situation in poplars, knowledge of sex determination mechanisms in willows is sparse. In the present study, we have for the first time positioned the sex determination locus on chromosome XV in S. viminalis using quantitative trait locus mapping. All female offspring carried a maternally inherited haplotype, suggesting a system of female heterogamety or ZW. We used a comparative mapping approach and compared the positions of the markers between the S. viminalis linkage map and the physical maps of S. purpurea, S. suchowensis and P. trichocarpa. As we found no evidence for chromosomal rearrangements between chromosome XV and XIX between S. viminalis and P. trichocarpa, it shows that the sex determination loci in the willow and the poplar most likely do not share a common origin and has thus evolved separately. This demonstrates that sex determination mechanisms in the Salicaceae family have a high turnover rate and as such it is excellent for studies of evolutionary processes involved in sex chromosome turnover.

  19. Single locus sex determination and female heterogamety in the basket willow (Salix viminalis L.)

    PubMed Central

    Pucholt, P; Rönnberg-Wästljung, A-C; Berlin, S

    2015-01-01

    Most eukaryotes reproduce sexually and a wealth of different sex determination mechanisms have evolved in this lineage. Dioecy or separate sexes are rare among flowering plants but have repeatedly evolved from hermaphroditic ancestors possibly involving male or female sterility mutations. Willows (Salix spp.) and poplars (Populus spp.) are predominantly dioecious and are members of the Salicaceae family. All studied poplars have sex determination loci on chromosome XIX, however, the position differs among species and both male and female heterogametic system exists. In contrast to the situation in poplars, knowledge of sex determination mechanisms in willows is sparse. In the present study, we have for the first time positioned the sex determination locus on chromosome XV in S. viminalis using quantitative trait locus mapping. All female offspring carried a maternally inherited haplotype, suggesting a system of female heterogamety or ZW. We used a comparative mapping approach and compared the positions of the markers between the S. viminalis linkage map and the physical maps of S. purpurea, S. suchowensis and P. trichocarpa. As we found no evidence for chromosomal rearrangements between chromosome XV and XIX between S. viminalis and P. trichocarpa, it shows that the sex determination loci in the willow and the poplar most likely do not share a common origin and has thus evolved separately. This demonstrates that sex determination mechanisms in the Salicaceae family have a high turnover rate and as such it is excellent for studies of evolutionary processes involved in sex chromosome turnover. PMID:25649501

  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. 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.

  2. Speaking rate effects on locus equation slope.

    PubMed

    Berry, Jeff; Weismer, Gary

    2013-11-01

    A locus equation describes a 1st order regression fit to a scatter of vowel steady-state frequency values predicting vowel onset frequency values. Locus equation coefficients are often interpreted as indices of coarticulation. Speaking rate variations with a constant consonant-vowel form are thought to induce changes in the degree of coarticulation. In the current work, the hypothesis that locus slope is a transparent index of coarticulation is examined through the analysis of acoustic samples of large-scale, nearly continuous variations in speaking rate. Following the methodological conventions for locus equation derivation, data pooled across ten vowels yield locus equation slopes that are mostly consistent with the hypothesis that locus equations vary systematically with coarticulation. Comparable analyses between different four-vowel pools reveal variations in the locus slope range and changes in locus slope sensitivity to rate change. Analyses across rate but within vowels are substantially less consistent with the locus hypothesis. Taken together, these findings suggest that the practice of vowel pooling exerts a non-negligible influence on locus outcomes. Results are discussed within the context of articulatory accounts of locus equations and the effects of speaking rate change.

  3. Molecular mapping of chromosomes 17 and X. Progress report

    SciTech Connect

    Barker, D.F.

    1989-12-31

    The basic aims of this project are the construction of high density genetic maps of chromosomes 17 and X and the utilization of these maps for the subsequent isolation of a set of physically overlapping DNA segment clones. The strategy depends on the utilization of chromosome specific libraries of small (1--15 kb) segments from each of the two chromosomes. Since the time of submission of our previous progress report, we have refined the genetic map of markers which we had previously isolated for chromosome 17. We have completed our genetic mapping in CEPH reference and NF1 families of 15 markers in the pericentric region of chromosome 17. Physical mapping results with three probes, were shown be in very close genetic proximity to the NF1 gene, with respect to two translocation breakpoints which disrupt the activity of the gene. All three of the probes were found to lie between the centromere and the most proximal translocation breakpoint, providing important genetic markers proximal to the NF1 gene. Our primary focus has shifted to the X chromosome. We have isolated an additional 30 polymorphic markers, bringing the total number we have isolated to over 80. We have invested substantial effort in characterizing the polymorphisms at each of these loci and constructed plasmid subclones which reveal the polymorphisms for nearly all of the loci. These subclones are of practical value in that they produce simpler and stronger patterns on human genomic Southern blots, thus improving the efficiency of the genetic mapping experiments. These subclones may also be of value for deriving DNA sequence information at each locus, necessary for establishing polymerase chain reaction primers specific for each locus. Such information would allow the use of each locus as a sequence tagged site.

  4. Chromosome 14 and late-onset familial alzheimer disease (FAD)

    SciTech Connect

    Schellenberg, G.D.; Anderson, L.; Nemens, E.; Bird, T.D.; Wijsman, E.M.; Martin, G.M.; Payami, H.; Orr, H.T.; White, J.A.; Alonso, M.E.

    1993-09-01

    Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analysis were used, in 49 families with a mean age at onset [>=]60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependent penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score [>=]2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P<.02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset [>=]60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. 37 refs., 1 fig., 6 tabs.

  5. Molecular studies of translocations and trisomy involving chromosome 13

    SciTech Connect

    Robinson, W.P.; Bernasconi, F.; Dutly, F.; Schinzel, A.A.

    1996-01-11

    Twenty-four cases of trisomy 13 and one case with disomy 13, but a de novo dic(13,13)(p12p12) chromosome, were examined with molecular markers to determine the origin of the extra (or rearranged) chromosome. Twenty-one of 23 informative patients were consistent with a maternal origin of the extra chromosome. Lack of a third allele at any locus in both paternal origin cases indicate a somatic duplication of the paternal chromosome occurred. Five cases had translocation trisomy. The patient with a paternal rob(13q14q) had a maternal meiotic origin of the trisomy; thus, the paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13q14q) carrier and most trisomies are maternal in origin, this result should not be surprising; however, it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. Lack of a third allele at any locus in one of the three t(13q13q) cases indicates that it was most likely an isochromosome of postmeiotic origin, whereas the other two cases showed evidence of recombination. One balanced (nontrisomic) case with a nonmosaic 45, -13, -13, +t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologues, as has been found for all balanced homologous Robertsonian translocations so far investigated. Thus, it is also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. Despite a maternal origin of the trisomy, we cannot therefore infer anything about the parental origin of the chromosomes 13 and 14 involved in the translocation in the de novo t(13q14q) case nor for the two t(13;13) chromosomes showing a meiotic origin of the trisomy. 30 refs., 1 fig., 2 tabs.

  6. CTCF-mediated reduction of vigilin binding affects the binding of HP1α to the satellite 2 locus.

    PubMed

    Shen, Wen-Yan; Liu, Qiu-Ying; Wei, Ling; Yu, Xiao-Qin; Li, Ran; Yang, Wen-Li; Xie, Xiao-Yan; Liu, Wen-Quan; Huang, Yuan; Qin, Yang

    2014-05-01

    CCCTC-binding factor (CTCF) has been implicated in numerous aspects of chromosome biology, and vigilin, a multi-KH-domain protein, participates in heterochromatin formation and chromosome segregation. We previously showed that CTCF interacts with vigilin. Here, we show that human vigilin, but not CTCF, colocalizes with HP1α on heterochromatic satellite 2 and β-satellite repeats. CTCF up-regulates the transcription of satellite 2, while vigilin down-regulates it. Vigilin depletion or CTCF overexpression reduces the binding of HP1α on the satellite 2 locus. Furthermore, overexpression of CTCF resists the loading of vigilin onto the satellite 2 locus. Thus CTCF may regulate vigilin behavior and thus indirectly influence the binding of HP1α to the satellite 2 locus.

  7. Linkage disequilibrium utilized to establish a refined genetic position of the Salla disease locus on 6q14-q15

    SciTech Connect

    Schleutker, J.; Laine, A.P.; Haataja, L. |

    1995-05-20

    Salla disease (SD), an inherited free sialic acid storage disorder, is caused by impaired transport of free sialic acid across the lyosomal membrane. Clinical characteristics of the disease include severe psychomotor retardation and some neurological abnormalities. The authors report detailed linkage analyses of 50 Finnish SD families that localize the SD disease gene to a refined chromosomal area on 6q14-q15. The highest lod score of 17.30 was obtained with a microsatellite marker of locus D6S280. When linkage disequilibrium was adopted in the linkage analyses, they could further assign the SD locus to the immediate vicinity of marker locus D6S406. Linkage disequilibrium facilitated further restriction of the critical chromosomal region to approximately 80 kb, well within the limits of positional cloning techniques. 31 refs., 3 figs., 3 tabs.

  8. 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.

  9. Physical Modeling of Dynamic Coupling between Chromosomal Loci.

    PubMed

    Lampo, Thomas J; Kennard, Andrew S; Spakowitz, Andrew J

    2016-01-19

    The motion of chromosomal DNA is essential to many biological processes, including segregation, transcriptional regulation, recombination, and packaging. Physical understanding of these processes would be dramatically enhanced through predictive, quantitative modeling of chromosome dynamics of multiple loci. Using a polymer dynamics framework, we develop a prediction for the correlation in the velocities of two loci on a single chromosome or otherwise connected by chromatin. These predictions reveal that the signature of correlated motion between two loci can be identified by varying the lag time between locus position measurements. In general, this theory predicts that as the lag time interval increases, the dual-loci dynamic behavior transitions from being completely uncorrelated to behaving as an effective single locus. This transition corresponds to the timescale of the stress communication between loci through the intervening segment. This relatively simple framework makes quantitative predictions based on a single timescale fit parameter that can be directly compared to the in vivo motion of fluorescently labeled chromosome loci. Furthermore, this theoretical framework enables the detection of dynamically coupled chromosome regions from the signature of their correlated motion.

  10. Physical Modeling of Dynamic Coupling between Chromosomal Loci.

    PubMed

    Lampo, Thomas J; Kennard, Andrew S; Spakowitz, Andrew J

    2016-01-19

    The motion of chromosomal DNA is essential to many biological processes, including segregation, transcriptional regulation, recombination, and packaging. Physical understanding of these processes would be dramatically enhanced through predictive, quantitative modeling of chromosome dynamics of multiple loci. Using a polymer dynamics framework, we develop a prediction for the correlation in the velocities of two loci on a single chromosome or otherwise connected by chromatin. These predictions reveal that the signature of correlated motion between two loci can be identified by varying the lag time between locus position measurements. In general, this theory predicts that as the lag time interval increases, the dual-loci dynamic behavior transitions from being completely uncorrelated to behaving as an effective single locus. This transition corresponds to the timescale of the stress communication between loci through the intervening segment. This relatively simple framework makes quantitative predictions based on a single timescale fit parameter that can be directly compared to the in vivo motion of fluorescently labeled chromosome loci. Furthermore, this theoretical framework enables the detection of dynamically coupled chromosome regions from the signature of their correlated motion. PMID:26789757

  11. Loss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13

    SciTech Connect

    Lundberg, C.; Skoog, L.; Cavenee, W.K.; Nordenskjoeld, M.

    1987-04-01

    The genotypes at chromosomal loci defined by recombinant DNA probes revealing restriction fragment length polymorphisms were determined in constitutional and tumor tissue from 10 cases of ductal breast cancer: eight premenopausal females and two males. Somatic loss of constitutional heterozygosity was observed at loci on chromosome 13 in primary tumor tissue from three females and one male. In two cases, specific loss of heterozygosity at three distinct genetic loci along the length of the chromosome was observed. In another case, concurrent loss of alleles at loci on chromosomes 2, 13, 14, and 20 was detected, whereas a fourth case showed loss of heterozygosity for chromosomes 5 and 13. In each instance, the data were consistent with loss of one of the homologous chromosomes by mitotic nondisjunction. Analysis of loci on several other chromosomes showed retention of constitutional heterozygosity suggesting the relative specificity of the events. In contrast, similar analyses of other breast cancers, including comedocarcinoma, medullary carcinoma, and juvenile secretory carcinoma, showed no loss of alleles at loci on chromosome 13. These data indicate that the pathogenesis of ductal breast cancer may, in a substantial proportion of cases, involve unmasking of a recessive locus on chromosome 13 and suggest the involvement of such a locus in heritable forms of this disease.

  12. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13

    SciTech Connect

    Wooster, R.; Mangion, J.; Quirk, Y.; Collins, N.; Seal, S.; Ford, D.; Averill, D. ); Neuhausen, S.L.; Nguyen, K.; Tran, T. )

    1994-09-30

    A small proportion of breast cancer, in particular those cases arising at a young age, is due to the inheritance of dominant susceptibility genes conferring a high risk of the disease. A genomic linkage search was performed with 15 high-risk breast cancer families that were unlinked to the BRCA1 locus on chromosome 17q21. This analysis localized a second breast cancer susceptibility locus, BRCA2, to a 6-centimorgan interval on chromosome 13q12-13. Preliminary, evidence suggests that BRCA2 confers a high risk of breast cancer but, unlike BRCA1, does not confer a substantially elevated risk of ovarian cancer.

  13. Two genetic markers closely linked to adult polycystic kidney disease on chromosome 16.

    PubMed Central

    Reeders, S T; Breuning, M H; Corney, G; Jeremiah, S J; Meera Khan, P; Davies, K E; Hopkinson, D A; Pearson, P L; Weatherall, D J

    1986-01-01

    The genetic locus for autosomal dominant adult polycystic kidney disease was recently assigned to chromosome 16 by the finding of genetic linkage to the alpha globin gene cluster. Further study showed that the phosphoglycolate phosphatase locus is also closely linked to both the locus for adult polycystic kidney disease and the alpha globin gene cluster. These findings have important implications for the prenatal and presymptomatic diagnosis of adult polycystic kidney disease and for a better understanding of its pathogenesis. Images FIG 1 PMID:3008903

  14. Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q

    SciTech Connect

    Detera-Wadleigh, S.D.; Badner, J.A.; Goldin, L.R.

    1996-06-01

    In 22 multiplex pedigrees screened for linkage to bipolar disorder, by use of 18 markers on chromosome 21q, single-locus affected-sib-pair (ASP) analysis detected a high proportion (57%-62%) of alleles shared identical by descent (IBD), with P values of .049-.0008 on nine marker loci. Multilocus ASP analyses revealed locus trios in the distal region between D21S270 and D21S171, with excess allele sharing (nominal P values <.01) under two affection-status models, ASM I (bipolars and schizoaffectives) and ASM II (ASM I plus recurrent unipolars). In addition, under ASM I, the proximal interval spanned by D21S1436 and D21S65 showed locus trios with excess allele sharing (nominal P values of .03-.0003). These findings support prior evidence that a susceptibility locus for bipolar disorder is on 21q. 38 refs., 4 tabs.

  15. Evidence for an association between non-syndromic cleft lip with or without cleft palate and a gene located on the long arm of chromosome 4

    SciTech Connect

    Healey, S.C.; Chenevix-Trench, G.; Mitchell, L.E.

    1994-09-01

    Evidence of linkage has been reported for non-syndromic cleft lip with or without cleft palate (CL{+-}P) and two markers (D4S175 and D4S192) in the region 4q25-4q31.3. The linkage evidence comes from a single Caucasian pedigree with multiple cases of CL{+-}P in five generations. High-density pedigrees are, however, atypical of CL{+-}P and linkage evidence obtained from such a family may not be relevant to the majority of CL{+-}P families. We have, therefore, examined the association of CL{+-}P with both D4S175 and D4S192 in 95 unrelated CL{+-}P patients and 161 unselected controls. There was no evidence for an association between D4S175 and CL{+-}P in these data. There was, however, a significant association between D4S192 and CL{+-}P ({chi}{sup 2}{sub 4}=15.5,P=0.006), and the genotypic distribution was significantly heterogeneous between CL{+-}P patients and controls (P=0.025). Comparison of each of the four most common alleles (i.e A87, A89, A91 and A95), to all other alleles combined, indicated that A87 was significantly less common (OR=0.56,95% C.I. 0.34-0.90), and A95 was significantly more common (OR=1.88,95% C.I. 1.03-3.43) among the CL{+-}P patients than the controls. Although of only borderline significance, A89 also appeared to be more common among patients than controls (OR=1.43,95% C.I. 0.99-2.60). Hence, it appears that genetic variation at a CL{+-}P susceptibility locus (CSL) linked to D4S192 may be associated with both increased and decreased risk of CL{+-}P. In combination, A89 and A95 are significantly more common in CL{+-}P patients than in controls (OR=1.80;95% C.I. 1.24-2.60) and account for a risk ratio of 1.08 in the first degree relatives of CL{+-}P patients. These results provide further evidence for the presence of a CSL in the region 4q25-4q31.1, and indicate that the putative CSL is located closer to D4S192 than to D4S175.

  16. Extinction of albumin gene expression in a panel of human chromosome 2 microcell hybrids

    SciTech Connect

    Cerosaletti, K.M.; Fournier, R.E.K.

    1996-02-01

    Expression of the serum albumin gene is extinguished in rat hepatoma microcell hybrids that retain mouse chromosome 1. These data define a trans-dominant extinguisher locus, Tse-2, on mouse chromosome 1. To localize the human TSE2 locus, we prepared and characterized rat/human microcell hybrids that contained either human chromosome 1 or chromosome 2, the genetic homologues of mouse chromosome 1. Rat hepatoma microcell hybrids retaining a derivative human chromosome 1 [der 1 t(1;17)(p34.3;q11.2)] expressed their serum albumin genes at levels similar to those of parental hepatoma cells. In contrast, microcell transfer of human chromosome 2 into rat hepatoma recipients produced karyotypically heterogeneous collections of hybrid clones, some of which displayed dramatic albumin extinction phenotypes. For example, albumin mRNA levels in hapatoma x fibroblast whole-cell hybrids. Expression of several other liver genes, including {alpha}1-antitrypsin, aldolase B, alcohol dehydrogenase, and phosphoenolpyruvate carboxykinase, was also affected in some of the microcell hybrids, but expression of these genes was no concordant with expression of albumin. Hybrid segregants were prepared from the albumin-extinguished hybrids, and reexpression of albumin mRNA and protein was observed in sublines that had lost or fragmented human chromosome 2. Finally, expression of mRNAs encoding the liver-enriched transactivators HNF-1, HNF-4, HNF-3{alpha}, and HNF-3{beta} was not affected in any of the chromosome 2-containing hybrids. These data define and map a genetic locus on human chromosome 2 that extinguishes albumin gene expression in trans, and they suggest that TSE2-mediated extinction is independent of HNF-1, -4, -3{alpha}, and -3{beta} expression. 61 refs., 2 figs., 3 tabs.

  17. Analysis of morphine responses in mice reveals a QTL on Chromosome 7

    PubMed Central

    Crusio, Wim E.; Dhawan, Esha; Chesler, Elissa J.; Delprato, Anna

    2016-01-01

    In this study we identified a quantitative trait locus (QTL) on mouse Chromosome 7 associated with locomotor activity and rearing post morphine treatment. This QTL was revealed after correcting for the effects of another QTL peak on Chromosome 10 using composite interval mapping. The positional candidate genes are Syt9 and Ppfibp2. Several other genes within the interval are linked to neural processes, locomotor activity, and the defensive response to harmful stimuli. PMID:27746909

  18. Polymer physics of chromosome large-scale 3D organisation

    NASA Astrophysics Data System (ADS)

    Chiariello, Andrea M.; Annunziatella, Carlo; Bianco, Simona; Esposito, Andrea; Nicodemi, Mario

    2016-07-01

    Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.

  19. Polymer physics of chromosome large-scale 3D organisation

    PubMed Central

    Chiariello, Andrea M.; Annunziatella, Carlo; Bianco, Simona; Esposito, Andrea; Nicodemi, Mario

    2016-01-01

    Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding. PMID:27405443

  20. Polymer physics of chromosome large-scale 3D organisation.

    PubMed

    Chiariello, Andrea M; Annunziatella, Carlo; Bianco, Simona; Esposito, Andrea; Nicodemi, Mario

    2016-01-01

    Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.

  1. Physical mapping of a pollen modifier locus controlling self-incompatibility in apricot and synteny analysis within the Rosaceae.

    PubMed

    Zuriaga, Elena; Molina, Laura; Badenes, María Luisa; Romero, Carlos

    2012-06-01

    S-locus products (S-RNase and F-box proteins) are essential for the gametophytic self-incompatibility (GSI) specific recognition in Prunus. However, accumulated genetic evidence suggests that other S-locus unlinked factors are also required for GSI. For instance, GSI breakdown was associated with a pollen-part mutation unlinked to the S-locus in the apricot (Prunus armeniaca L.) cv. 'Canino'. Fine-mapping of this mutated modifier gene (M-locus) and the synteny analysis of the M-locus within the Rosaceae are here reported. A segregation distortion loci mapping strategy, based on a selectively genotyped population, was used to map the M-locus. In addition, a bacterial artificial chromosome (BAC) contig was constructed for this region using overlapping oligonucleotides probes, and BAC-end sequences (BES) were blasted against Rosaceae genomes to perform micro-synteny analysis. The M-locus was mapped to the distal part of chr.3 flanked by two SSR markers within an interval of 1.8 cM corresponding to ~364 Kb in the peach (Prunus persica L. Batsch) genome. In the integrated genetic-physical map of this region, BES were mapped against the peach scaffold_3 and BACs were anchored to the apricot map. Micro-syntenic blocks were detected in apple (Malus × domestica Borkh.) LG17/9 and strawberry (Fragaria vesca L.) FG6 chromosomes. The M-locus fine-scale mapping provides a solid basis for self-compatibility marker-assisted selection and for positional cloning of the underlying gene, a necessary goal to elucidate the pollen rejection mechanism in Prunus. In a wider context, the syntenic regions identified in peach, apple and strawberry might be useful to interpret GSI evolution in Rosaceae.

  2. The Lbw2 locus promotes autoimmune hemolytic anemia.

    PubMed

    Scatizzi, John C; Haraldsson, Maria K; Pollard, K Michael; Theofilopoulos, Argyrios N; Kono, Dwight H

    2012-04-01

    The lupus-prone New Zealand Black (NZB) strain uniquely develops a genetically imposed severe spontaneous autoimmune hemolytic anemia (AIHA) that is very similar to the corresponding human disease. Previous studies have mapped anti-erythrocyte Ab (AEA)-promoting NZB loci to several chromosomal locations, including chromosome 4; however, none of these have been analyzed with interval congenics. In this study, we used NZB.NZW-Lbw2 congenic (designated Lbw2 congenic) mice containing an introgressed fragment of New Zealand White (NZW) on chromosome 4 encompassing Lbw2, a locus previously linked to survival, glomerulonephritis, and splenomegaly, to investigate its role in AIHA. Lbw2 congenic mice exhibited marked reductions in AEAs and splenomegaly but not in anti-nuclear Abs. Furthermore, Lbw2 congenics had greater numbers of marginal zone B cells and reduced expansion of peritoneal cells, particularly the B-1a cell subset at early ages, but no reduction in B cell response to LPS. Analysis of a panel of subinterval congenic mice showed that the full effect of Lbw2 on AEA production was dependent on three subloci, with splenomegaly mapping to two of the subloci and expansions of peritoneal cell populations, including B-1a cells to one. These results directly demonstrated the presence of AEA-specific promoting genes on NZB chromosome 4, documented a marked influence of background genes on autoimmune phenotypes related to Lbw2, and further refined the locations of the underlying genetic variants. Delineation of the Lbw2 genes should yield new insights into both the pathogenesis of AIHA and the nature of epistatic interactions of lupus-modifying genetic variants.

  3. Genetic and physical maps around the sex-determining M-locus of the dioecious plant asparagus.

    PubMed

    Telgmann-Rauber, Alexa; Jamsari, Ari; Kinney, Michael S; Pires, J Chris; Jung, Christian

    2007-09-01

    Asparagus officinalis L. is a dioecious plant. A region called the M-locus located on a pair of homomorphic sex chromosomes controls the sexual dimorphism in asparagus. The aim of this work was to clone the region determining sex in asparagus from its position in the genome. The structure of the region encompassing M should be investigated and compared to the sex-determining regions in other dioecious model species. To establish an improved basis for physical mapping, a high-resolution genetic map was enriched with AFLP markers closely linked to the target locus by carrying out a bulked segregant analysis. By screening a BAC library with AFLP- and STS-markers followed by chromosome walking, a physical map with eight contigs could be established. However, the gaps between the contigs could not be closed due to a plethora of repetitive elements. Surprisingly, two of the contigs on one side of the M-locus did not overlap although they have been established with two markers, which mapped in a distance as low as 0.25 cM flanking the sex locus. Thus, the clustering of the markers indicates a reduced recombination frequency within the M-region. On the opposite side of the M-locus, a contig was mapped in a distance of 0.38 cM. Four closely linked BAC clones were partially sequenced and 64 putative ORFs were identified. Interestingly, only 25% of the ORFs showed sequence similarity to known proteins and ESTs. In addition, an accumulation of repetitive sequences and a low gene density was revealed in the sex-determining region of asparagus. Molecular cytogenetic and sequence analysis of BACs flanking the M-locus indicate that the BACs contain highly repetitive sequences that localize to centromeric and pericentromeric locations on all asparagus chromosomes, which hindered the localization of the M-locus to the single pair of sex chromosomes. We speculate that dioecious Silene, papaya and Asparagus species may represent three stages in the evolution of XX, XY sex

  4. Genetic and physical maps around the sex-determining M-locus of the dioecious plant asparagus.

    PubMed

    Telgmann-Rauber, Alexa; Jamsari, Ari; Kinney, Michael S; Pires, J Chris; Jung, Christian

    2007-09-01

    Asparagus officinalis L. is a dioecious plant. A region called the M-locus located on a pair of homomorphic sex chromosomes controls the sexual dimorphism in asparagus. The aim of this work was to clone the region determining sex in asparagus from its position in the genome. The structure of the region encompassing M should be investigated and compared to the sex-determining regions in other dioecious model species. To establish an improved basis for physical mapping, a high-resolution genetic map was enriched with AFLP markers closely linked to the target locus by carrying out a bulked segregant analysis. By screening a BAC library with AFLP- and STS-markers followed by chromosome walking, a physical map with eight contigs could be established. However, the gaps between the contigs could not be closed due to a plethora of repetitive elements. Surprisingly, two of the contigs on one side of the M-locus did not overlap although they have been established with two markers, which mapped in a distance as low as 0.25 cM flanking the sex locus. Thus, the clustering of the markers indicates a reduced recombination frequency within the M-region. On the opposite side of the M-locus, a contig was mapped in a distance of 0.38 cM. Four closely linked BAC clones were partially sequenced and 64 putative ORFs were identified. Interestingly, only 25% of the ORFs showed sequence similarity to known proteins and ESTs. In addition, an accumulation of repetitive sequences and a low gene density was revealed in the sex-determining region of asparagus. Molecular cytogenetic and sequence analysis of BACs flanking the M-locus indicate that the BACs contain highly repetitive sequences that localize to centromeric and pericentromeric locations on all asparagus chromosomes, which hindered the localization of the M-locus to the single pair of sex chromosomes. We speculate that dioecious Silene, papaya and Asparagus species may represent three stages in the evolution of XX, XY sex

  5. Systematic chromosome examination of two families with schizophrenia and two families with manic depressive illness

    SciTech Connect

    Friedrich, U.; Mors, O.; Ewald, H.

    1996-02-16

    Systematic and detailed chromosome analysis, combined with a semistructured interview, was performed in 2 families with schizophrenia and in 2 families with manic depressive illness. Prometaphase technique did not reveal any subtle structural chromosome abnormalities. However, in standard techniques, gain and loss of sex chromosomes were observed. This occurred in patients at a younger age than in unaffected persons. This gives rise to the suspicion that sex chromosome aneuploidy may somehow be related to the development of psychosis. But since the data set is small, especially with respect to schizophrenia, further studies are needed to elucidate this observation. In one family, cosegregation of the disease locus with a marker on chromosome 21 was seen. Therefore, further research should determine if chromosome 21 contains a gene for manic depressive illness. 10 refs., 3 figs., 2 tabs.

  6. 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

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

    PubMed

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

    2008-12-01

    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 approximately 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.

  8. Human immunoglobulin VH and D segments on chromosomes 15q11.2 and 16p11.2.

    PubMed

    Tomlinson, I M; Cook, G P; Carter, N P; Elaswarapu, R; Smith, S; Walter, G; Buluwela, L; Rabbitts, T H; Winter, G

    1994-06-01

    In addition to the major human immunoglobulin heavy-chain locus on chromosome 14q32.3, VH and D segments are known to be present on chromosomes 15 and 16. We have now amplified and sequenced 24 such VH segments from somatic cell hybrids and have assigned them to 15q11.2 and 16p11.2 using cosmid and yeast artificial chromosome clones. In addition, we have located a cluster of D segments on 15q11.2, previously thought to be located on 14q32.3. We propose that the segments on chromosome 16 arose by an interchromosomal duplication and identify the corresponding region on chromosome 14. Taken together with the completion of a map of the human VH locus on 14q32.3, the total number of VH segments now identified is 117. We can now account for most, if not all human germ-line VH segments. PMID:7951227

  9. Description and nomenclature of Neisseria meningitidis capsule locus.

    PubMed

    Harrison, Odile B; Claus, Heike; Jiang, Ying; Bennett, Julia S; Bratcher, Holly B; Jolley, Keith A; Corton, Craig; Care, Rory; Poolman, Jan T; Zollinger, Wendell D; Frasch, Carl E; Stephens, David S; Feavers, Ian; Frosch, Matthias; Parkhill, Julian; Vogel, Ulrich; Quail, Michael A; Bentley, Stephen D; Maiden, Martin C J

    2013-04-01

    Pathogenic Neisseria meningitidis isolates contain a polysaccharide capsule that is the main virulence determinant for this bacterium. Thirteen capsular polysaccharides have been described, and nuclear magnetic resonance spectroscopy has enabled determination of the structure of capsular polysaccharides responsible for serogroup specificity. Molecular mechanisms involved in N. meningitidis capsule biosynthesis have also been identified, and genes involved in this process and in cell surface translocation are clustered at a single chromosomal locus termed cps. The use of multiple names for some of the genes involved in capsule synthesis, combined with the need for rapid diagnosis of serogroups commonly associated with invasive meningococcal disease, prompted a requirement for a consistent approach to the nomenclature of capsule genes. In this report, a comprehensive description of all N. meningitidis serogroups is provided, along with a proposed nomenclature, which was presented at the 2012 XVIIIth International Pathogenic Neisseria Conference.

  10. A comprehensive analysis of the chorion locus in silkmoth

    PubMed Central

    Chen, Zhiwei; Nohata, Junko; Guo, Huizhen; Li, Shenglong; Liu, Jianqiu; Guo, Youbing; Yamamoto, Kimiko; Kadono-Okuda, Keiko; Liu, Chun; Arunkumar, Kallare P.; Nagaraju, Javaregowda; Zhang, Yan; Liu, Shiping; Labropoulou, Vassiliki; Swevers, Luc; Tsitoura, Panagiota; Iatrou, Kostas; Gopinathan, Karumathil P.; Goldsmith, Marian R.; Xia, Qingyou; Mita, Kazuei

    2015-01-01

    Despite more than 40 years of intense study, essential features of the silkmoth chorion (eggshell) are still not fully understood. To determine the precise structure of the chorion locus, we performed extensive EST analysis, constructed a bacterial artificial chromosome (BAC) contig, and obtained a continuous genomic sequence of 871,711 base pairs. We annotated 127 chorion genes in two segments interrupted by a 164 kb region with 5 non-chorion genes, orthologs of which were on chorion bearing scaffolds in 4 ditrysian families. Detailed transcriptome analysis revealed expression throughout choriogenesis of most chorion genes originally categorized as “middle”, and evidence for diverse regulatory mechanisms including cis-elements, alternative splicing and promoter utilization, and antisense RNA. Phylogenetic analysis revealed multigene family associations and faster evolution of early chorion genes and transcriptionally active pseudogenes. Proteomics analysis identified 99 chorion proteins in the eggshell and micropyle localization of 1 early and 6 Hc chorion proteins. PMID:26553298

  11. A comprehensive analysis of the chorion locus in silkmoth.

    PubMed

    Chen, Zhiwei; Nohata, Junko; Guo, Huizhen; Li, Shenglong; Liu, Jianqiu; Guo, Youbing; Yamamoto, Kimiko; Kadono-Okuda, Keiko; Liu, Chun; Arunkumar, Kallare P; Nagaraju, Javaregowda; Zhang, Yan; Liu, Shiping; Labropoulou, Vassiliki; Swevers, Luc; Tsitoura, Panagiota; Iatrou, Kostas; Gopinathan, Karumathil P; Goldsmith, Marian R; Xia, Qingyou; Mita, Kazuei

    2015-01-01

    Despite more than 40 years of intense study, essential features of the silkmoth chorion (eggshell) are still not fully understood. To determine the precise structure of the chorion locus, we performed extensive EST analysis, constructed a bacterial artificial chromosome (BAC) contig, and obtained a continuous genomic sequence of 871,711 base pairs. We annotated 127 chorion genes in two segments interrupted by a 164 kb region with 5 non-chorion genes, orthologs of which were on chorion bearing scaffolds in 4 ditrysian families. Detailed transcriptome analysis revealed expression throughout choriogenesis of most chorion genes originally categorized as "middle", and evidence for diverse regulatory mechanisms including cis-elements, alternative splicing and promoter utilization, and antisense RNA. Phylogenetic analysis revealed multigene family associations and faster evolution of early chorion genes and transcriptionally active pseudogenes. Proteomics analysis identified 99 chorion proteins in the eggshell and micropyle localization of 1 early and 6 Hc chorion proteins. PMID:26553298

  12. Hybrid male sterility in rice is due to epistatic interactions with a pollen killer locus.

    PubMed

    Kubo, Takahiko; Yoshimura, Atsushi; Kurata, Nori

    2011-11-01

    In intraspecific crosses between cultivated rice (Oryza sativa) subspecies indica and japonica, the hybrid male sterility gene S24 causes the selective abortion of male gametes carrying the japonica allele (S24-j) via an allelic interaction in the heterozygous hybrids. In this study, we first examined whether male sterility is due solely to the single locus S24. An analysis of near-isogenic lines (NIL-F(1)) showed different phenotypes for S24 in different genetic backgrounds. The S24 heterozygote with the japonica genetic background showed male semisterility, but no sterility was found in heterozygotes with the indica background. This result indicates that S24 is regulated epistatically. A QTL analysis of a BC(2)F(1) population revealed a novel sterility locus that interacts with S24 and is found on rice chromosome 2. The locus was named Epistatic Factor for S24 (EFS). Further genetic analyses revealed that S24 causes male sterility when in combination with the homozygous japonica EFS allele (efs-j). The results suggest that efs-j is a recessive sporophytic allele, while the indica allele (EFS-i) can dominantly counteract the pollen sterility caused by S24 heterozygosity. In summary, our results demonstrate that an additional epistatic locus is an essential element in the hybrid sterility caused by allelic interaction at a single locus in rice. This finding provides a significant contribution to our understanding of the complex molecular mechanisms underlying hybrid sterility and microsporogenesis.

  13. Genetic instability in Drosophila melanogaster: evidence for regulation, excision and transposition at the white locus.

    PubMed

    Rasmuson, B; Montell, I; Rasmuson, A; Svahlin, H; Westerberg, B M

    1980-01-01

    An unstable long tandem duplication which includes the white locus twice, marked with wsp in the left and w17g in the right locus, when kept in males has been found to produce red-eyed sons which have lost the long duplication and with it the wsp and w17g mutants. Such exceptions were produced also when w17g had been exchanged for wa. Stocks originating from these exceptions are unstable, producing: 1) zeste males, also unstable, 2) w- deletions, stable, 3) transpositions of the white locus to sites in other chromosomes. The instability is interpreted as the effect of an IS element, within or adjacent to the white locus, which is supposed to retain a duplication of the proximal zeste interacting part of this locus. According to the orientation of the IS element the duplicated part can be active or inactive, giving a zeste or red eye phenotype. The frequency of exceptional offspring after X-ray treatment of the red and zeste unstable stocks have been compared to stable stocks with corresponding genotypes. PMID:6247608

  14. Molecular cloning of the white locus region of Drosophila melanogaster using a large transposable element

    PubMed Central

    Goldberg, M.L.; Paro, R.; Gehring, W.J.

    1982-01-01

    We report the molecular cloning of a chromosome segment including the white locus of Drosophila melanogaster. This region was isolated using a deficiency extending from the previously cloned heat-shock puff sequences at 87A7 to a large transposable element containing the loci white and roughest.FB-NOF, a 7.5 kb element with partial homology to a family of inverted repeat sequences (Potter et al., 1980), is found very near the deficiency breakpoint, and is followed by DNA originating from the white locus region. Sequences totalling ˜60 kb surrounding this initial entry point were obtained by the cloning of successively overlapping fragments from a wild-type strain. Several rearrangement breakpoints have been mapped relative to the cloned DNA; these define the limits of the white locus and further differentiate the “white proximal region”, thought to function in gene regulation, from the remainder of the locus. Insertion of the dispersed repetitive element copia into the white locus is observed in strains carrying the white-apricot allele. Analysis of several white-apricot revertants suggests that copia insertion is responsible for the apricot eye color phenotype. ImagesFig. 2.Fig. 4.Fig. 5.Fig. 6. PMID:16453411

  15. Analysis of meiotic segregation, using single-sperm typing: Meiotic drive at the myotonic dystrophy locus

    SciTech Connect

    Leeflang, E.P.; Arnheim, N.; McPeek, M.S.

    1996-10-01

    Meiotic drive at the myotonic dystrophy (DM) locus has recently been suggested as being responsible for maintaining the frequency, in the human population, of DM chromosomes capable of expansion to the disease state. In order to test this hypothesis, we have studied samples of single sperm from three individuals heterozygous at the DM locus, each with one allele larger and one allele smaller than 19 CTG repeats. To guard against the possible problem of differential PCR amplification rates based on the lengths of the alleles, the sperm were also typed at another closely linked marker whose allele size was unrelated to the allele size at the DM locus. Using statistical models specifically designed to study single-sperm segregation data, we find no evidence of meiotic segregation distortion. The upper limit of the two-sided 95% confidence interval for the estimate of the common segregation probability for the three donors is at or below .515 for all models considered, and no statistically significant difference from .5 is detected in any of the models. This suggests that any greater amount of segregation distortion at the myotonic dystrophy locus must result from events following sperm ejaculation. The mathematical models developed make it possible to study segregation distortion with high resolution by using sperm-typing data from any locus. 26 refs., 1 fig., 8 tabs.

  16. The IgH locus 3' regulatory region: pulling the strings from behind.

    PubMed

    Pinaud, Eric; Marquet, Marie; Fiancette, Rémi; Péron, Sophie; Vincent-Fabert, Christelle; Denizot, Yves; Cogné, Michel

    2011-01-01

    Antigen receptor gene loci are among the most complex in mammals. The IgH locus, encoding the immunoglobulin heavy chain (IgH) in B-lineage cells, undergoes major transcription-dependent DNA remodeling events, namely V(D)J recombination, Ig class-switch recombination (CSR), and somatic hypermutation (SHM). Various cis-regulatory elements (encompassing promoters, enhancers, and chromatin insulators) recruit multiple nuclear factors in order to ensure IgH locus regulation by tightly orchestrated physical and/or functional interactions. Among major IgH cis-acting regions, the large 3' regulatory region (3'RR) located at the 3' boundary of the locus includes several enhancers and harbors an intriguing quasi-palindromic structure. In this review, we report progress insights made over the past decade in order to describe in more details the structure and functions of IgH 3'RRs in mouse and human. Generation of multiple cellular, transgenic and knock-out models helped out to decipher the function of the IgH 3' regulatory elements in the context of normal and pathologic B cells. Beside its interest in physiology, the challenge of elucidating the locus-wide cross talk between distant cis-regulatory elements might provide useful insights into the mechanisms that mediate oncogene deregulation after chromosomal translocations onto the IgH locus.

  17. The mouse BP-1 gene: Structure, chromosomal localization, and regulation of expression by type I interferons and interleukin-7

    SciTech Connect

    Wang, Jiyang; Walker, H.; Lin, Q.

    1996-04-15

    The BP-1/6C3 antigen is a homodimeric, phosphorylated type II membrane integral glycoprotein expressed on immature B-lineage cells, bone marrow stromal cells, thymic cortical epithelial cells, endothelial cells, thymic cortical epithelial cells, endothelial cells, thymic cortical epithelial cells, endothelial cells, enterocytes, and renal proximal tubular cells. Biochemical and molecular analysis identified BP-1 as glutamyl aminopeptidase, an ectoenzyme that catalyzes the hydrolysis of acidic amino acid residues from the amino termini of regulatory peptides. We have isolated genomic clones that encode the BP-1 gene (gene symbol Enpep). The gene spans more than 110 kb and contains 20 exons, it is composed of small exons ranging from 56 to 171 bp that are separated by introns ranging from less than 100 bp to approximately 10 kb. The zinc binding motif HEXXH and the glutamic acid residue 19 amino acids downstream, which also binds zinc, are encoded in exons 5 and 6. Primer extension analysis revealed a common major transcriptional start site in a pre-B cell line, in a bone marrow stromal cell line, and in kidney cells. An interferon responsive element also located in the promoter region appeared to be functional, since type I interferons (IFN-{alpha}/IFN-{beta}) upregulated BP-1 expression in pre-B cell lines. The BP-1/Enpep gene was localized to a distal region of mouse chromosome 3 in a region homologous to human chromosome 4q25. Interestingly, while interleukin-7 (IL-7) induced both cell growth and increased BP-1 expression, IFN-{alpha}/IFN-{beta} upregulated BP-1 expression but inhibited IL-7-induced proliferation. This finding indicates that the upregulated BP-1 expression can be disassociated from the cell growth signal. 48 refs., 7 figs., 1 tab.

  18. Surfeit locus gene homologs are widely distributed in invertebrate genomes.

    PubMed

    Armes, N; Fried, M

    1996-10-01

    The mouse Surfeit locus contains six sequence-unrelated genes (Surf-1 to -6) arranged in the tightest gene cluster so far described for mammals. The organization and juxtaposition of five of the Surfeit genes (Surf-1 to -5) are conserved between mammals and birds, and this may reflect a functional or regulatory requirement for the gene clustering. We have undertaken an evolutionary study to determine whether the Surfeit genes are conserved and clustered in invertebrate genomes. Drosophila melanogaster and Caenorhabditis elegans homologs of the mouse Surf-4 gene, which encodes an integral membrane protein associated with the endoplasmic reticulum, have been isolated. The amino acid sequences of the Drosophila and C. elegans homologs are highly conserved in comparison with the mouse Surf-4 protein. In particular, a dilysine motif implicated in endoplasmic reticulum localization of the mouse protein is conserved in the invertebrate homologs. We show that the Drosophila Surf-4 gene, which is transcribed from a TATA-less promoter, is not closely associated with other Drosophila Surfeit gene homologs but rather is located upstream from sequences encoding a homolog of a yeast seryl-tRNA synthetase protein. There are at least two closely linked Surf-3/rpL7a genes or highly polymorphic alleles of a single Surf-3/rpL7a gene in the C. elegans genome. The chromosomal locations of the C. elegans Surf-1, Surf-3/rpL7a, and Surf-4 genes have been determined. In D. melanogaster the Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs and in C. elegans the Surf-1, Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs are located on completely different chromosomes, suggesting that any requirement for the tight clustering of the genes in the Surfeit locus is restricted to vertebrate lineages.

  19. Chromosome 18 markers: Linked or not linked to bipolar affective disorders in the Old Order Amish? A reply to Gershon et al.

    SciTech Connect

    Pauls, D.L.; Ott, J.; Fann, C.S.J.; Paul, S.M.

    1996-06-01

    We appreciate the careful review of our paper by examining linkage of bipolar affective disorder (BAD) to markers on chromosome 18. These authors have raised several issues concerning our article and specifically challenge our conclusion concerning the presence or absence of a major susceptibility locus for BAD on chromosome 18 in the Old Order Amish sample. 9 refs.

  20. Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description.

    PubMed

    Yu, Guo-Yun; Mate, Suzanne; Garcia, Karla; Ward, Michael D; Brueggemann, Ernst; Hall, Matthew; Kenny, Tara; Sanchez-Lockhart, Mariano; Lefranc, Marie-Paule; Palacios, Gustavo

    2016-07-01

    Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development.

  1. Interchromosomal gene conversion at an endogenous human cell locus.

    PubMed Central

    Quintana, P J; Neuwirth, E A; Grosovsky, A J

    2001-01-01

    To examine the relationship between gene conversion and reciprocal exchange at an endogenous chromosomal locus, we developed a reversion assay in a thymidine kinase deficient mutant, TX545, derived from the human lymphoblastoid cell line TK6. Selectable revertants of TX545 can be generated through interchromosomal gene conversion at the site of inactivating mutations on each tk allele or by reciprocal exchange that alters the linkage relationships of inactivating polymorphisms within the tk locus. Analysis of loss of heterozygosity (LOH) at intragenic polymorphisms and flanking microsatellite markers was used to initially evaluate allelotypes in TK(+) revertants for patterns associated with either gene conversion or crossing over. The linkage pattern in a subset of convertants was then unambiguously established, even in the event of prereplicative recombinational exchanges, by haplotype analysis of flanking microsatellite loci in tk(-/-) LOH mutants collected from the tk(+/-) parental convertant. Some (7/38; 18%) revertants were attributable to easily discriminated nonrecombinational mechanisms, including suppressor mutations within the tk coding sequence. However, all revertants classified as a recombinational event (28/38; 74%) were attributed to localized gene conversion, representing a highly significant preference (P < 0.0001) over gene conversion with associated reciprocal exchange, which was never observed. PMID:11404339

  2. Sequence variation and haplotype structure at the human HFE locus.

    PubMed Central

    Toomajian, Christopher; Kreitman, Martin

    2002-01-01

    The HFE locus encodes an HLA class-I-type protein important in iron regulation and segregates replacement mutations that give rise to the most common form of genetic hemochromatosis. The high frequency of one disease-associated mutation, C282Y, and the nature of this disease have led some to suggest a selective advantage for this mutation. To investigate the context in which this mutation arose and gain a better understanding of HFE genetic variation, we surveyed nucleotide variability in 11.2 kb encompassing the HFE locus and experimentally determined haplotypes. We fully resequenced 60 chromosomes of African, Asian, or European ancestry as well as one chimpanzee, revealing 41 variable sites and a nucleotide diversity of 0.08%. This indicates that linkage to the HLA region has not substantially increased the level of HFE variation. Although several haplotypes are shared between populations, one haplotype predominates in Asia but is nearly absent elsewhere, causing higher than average genetic differentiation among the three major populations. Our samples show evidence of intragenic recombination, so the scarcity of recombination events within the C282Y allele class is consistent with selection increasing the frequency of a young allele. Otherwise, the pattern of variability in this region does not clearly indicate the action of positive selection at this or linked loci. PMID:12196404

  3. Mapping of crown gall resistance locus Rcg1 in grapevine.

    PubMed

    Kuczmog, Anett; Galambos, Anikó; Horváth, Szabina; Mátai, Anikó; Kozma, Pál; Szegedi, Ernő; Putnoky, Péter

    2012-11-01

    Agrobacteria are efficient plant pathogens. They are able to transform plant cells genetically resulting in abnormal cell proliferation. Cultivars of Vitis vinifera are highly susceptible to many virulent Agrobacterium strains but certain wild Vitis species, including Vitis amurensis have resistant genotypes. Studies of the molecular background of such natural resistance are of special importance, not only for practical benefits in agricultural practice but also for understanding the role of plant genes in the transformation process. Earlier, crown gall resistance from V. amurensis was introgressed into V. vinifera through interspecific breeding and it was shown to be inherited as a single and dominant Mendelian trait. To develop this research further, towards understanding underlying molecular mechanisms, a mapping population was established, and resistance-coupled molecular DNA markers were identified by three different approaches. First, RAPD makers linked to the resistance locus (Rcg1) were identified, and on the basis of their DNA sequences, we developed resistance-coupled SCAR markers. However, localization of these markers in the grapevine genome sequence failed due to their similarity to many repetitive regions. Next, using SSR markers of the grapevine reference linkage map, location of the resistance locus was established on linkage group 15 (LG15). Finally, this position was supported further by developing new chromosome-specific markers and by the construction of the genetic map of the region including nine loci in 29.1 cM. Our results show that the closest marker is located 3.3 cM from the Rcg1 locus that may correspond to 576 kb. PMID:22801874

  4. Mapping of crown gall resistance locus Rcg1 in grapevine.

    PubMed

    Kuczmog, Anett; Galambos, Anikó; Horváth, Szabina; Mátai, Anikó; Kozma, Pál; Szegedi, Ernő; Putnoky, Péter

    2012-11-01

    Agrobacteria are efficient plant pathogens. They are able to transform plant cells genetically resulting in abnormal cell proliferation. Cultivars of Vitis vinifera are highly susceptible to many virulent Agrobacterium strains but certain wild Vitis species, including Vitis amurensis have resistant genotypes. Studies of the molecular background of such natural resistance are of special importance, not only for practical benefits in agricultural practice but also for understanding the role of plant genes in the transformation process. Earlier, crown gall resistance from V. amurensis was introgressed into V. vinifera through interspecific breeding and it was shown to be inherited as a single and dominant Mendelian trait. To develop this research further, towards understanding underlying molecular mechanisms, a mapping population was established, and resistance-coupled molecular DNA markers were identified by three different approaches. First, RAPD makers linked to the resistance locus (Rcg1) were identified, and on the basis of their DNA sequences, we developed resistance-coupled SCAR markers. However, localization of these markers in the grapevine genome sequence failed due to their similarity to many repetitive regions. Next, using SSR markers of the grapevine reference linkage map, location of the resistance locus was established on linkage group 15 (LG15). Finally, this position was supported further by developing new chromosome-specific markers and by the construction of the genetic map of the region including nine loci in 29.1 cM. Our results show that the closest marker is located 3.3 cM from the Rcg1 locus that may correspond to 576 kb.

  5. Genetic Locus for Streptolysin S Production by Group A Streptococcus

    PubMed Central

    Nizet, Victor; Beall, Bernard; Bast, Darrin J.; Datta, Vivekananda; Kilburn, Laurie; Low, Donald E.; De Azavedo, Joyce C. S.

    2000-01-01

    Group A streptococcus (GAS) is an important human pathogen that causes pharyngitis and invasive infections, including necrotizing fasciitis. Streptolysin S (SLS) is the cytolytic factor that creates the zone of beta-hemolysis surrounding GAS colonies grown on blood agar. We recently reported the discovery of a potential genetic determinant involved in SLS production, sagA, encoding a small peptide of 53 amino acids (S. D. Betschel, S. M. Borgia, N. L. Barg, D. E. Low, and J. C. De Azavedo, Infect. Immun. 66:1671–1679, 1998). Using transposon mutagenesis, chromosomal walking steps, and data from the GAS genome sequencing project (www.genome.ou.edu/strep.html), we have now identified a contiguous nine-gene locus (sagA to sagI) involved in SLS production. The sag locus is conserved among GAS strains regardless of M protein type. Targeted plasmid integrational mutagenesis of each gene in the sag operon resulted in an SLS-negative phenotype. Targeted integrations (i) upstream of the sagA promoter and (ii) downstream of a terminator sequence after sagI did not affect SLS production, establishing the functional boundaries of the operon. A rho-independent terminator sequence between sagA and sagB appears to regulate the amount of sagA transcript produced versus transcript for the entire operon. Reintroduction of the nine-gene sag locus on a plasmid vector restored SLS activity to the nonhemolytic sagA knockout mutant. Finally, heterologous expression of the intact sag operon conferred the SLS beta-hemolytic phenotype to the nonhemolytic Lactococcus lactis. We conclude that gene products of the GAS sag operon are both necessary and sufficient for SLS production. Sequence homologies of sag operon gene products suggest that SLS is related to the bacteriocin family of microbial toxins. PMID:10858242

  6. The Ph1 locus of wheat does not discriminate between identical and non-identical homologues in rye.

    PubMed

    Oleszczuk, S; Tyrka, M; Lukaszewski, A J

    2014-01-01

    The main locus responsible for diploid-like behavior of polyploid wheat in meiosis, Ph1, is located on the long arm of chromosome 5B (5BL). It restricts metaphase I pairing to essentially identical homologues. Introduction of 5BL into outcrossing autotetraploid rye severely reduced multivalent formation and increased the frequency of bivalents and univalents, but the key by which homologues were selected for effective pairing was not clear. We created doubled haploids of autotetraploid rye with the long arm of wheat 5BL, verified their nature by DNA markers, and analyzed metaphase I chromosome pairing. The doubled haploid nature guaranteed the presence of pairs of identical and non-identical homologues in each homologous group. The metaphase I pairing patterns were essentially the same as in plants from open pollination, with frequent bivalents and univalents and rare multivalents. The level of pairing was low and depended on the dosage of 5BL. The pairing levels show that unlike in wheat, in rye the Ph1 locus does not use homologue similarity as the criterion in selection of pairing partners. It is possible that the Ph1 of wheat and the rye chromosome pairing system are mutually exclusive. The minimum level of chromosome differences required for effective pairing in rye may be well above the maximum difference level tolerated by the Ph1 system of wheat. In other words, effective chromosome pairing in rye may be possible between non-identical chromosomes that might not normally pair in the Ph1 wheat background.

  7. Factors Determining Adolescent Locus of Control.

    ERIC Educational Resources Information Center

    Kopera-Frye, Karen F.; And Others

    Previous research has demonstrated an association between locus of control in adolescence and a successful transition to adulthood. Having an external locus of control has been implicated as an important factor in adolescent behaviors such as teenage pregnancy and delinquency, and has been found to be negatively related to school achievement. This…

  8. CCCTC-binding factor (CTCF) and cohesin influence the genomic architecture of the Igh locus and antisense transcription in pro-B cells.

    PubMed

    Degner, Stephanie C; Verma-Gaur, Jiyoti; Wong, Timothy P; Bossen, Claudia; Iverson, G Michael; Torkamani, Ali; Vettermann, Christian; Lin, Yin C; Ju, Zhongliang; Schulz, Danae; Murre, Caroline S; Birshtein, Barbara K; Schork, Nicholas J; Schlissel, Mark S; Riblet, Roy; Murre, Cornelis; Feeney, Ann J

    2011-06-01

    Compaction and looping of the ~2.5-Mb Igh locus during V(D)J rearrangement is essential to allow all V(H) genes to be brought in proximity with D(H)-J(H) segments to create a diverse antibody repertoire, but the proteins directly responsible for this are unknown. Because CCCTC-binding factor (CTCF) has been demonstrated to be involved in long-range chromosomal interactions, we hypothesized that CTCF may promote the contraction of the Igh locus. ChIP sequencing was performed on pro-B cells, revealing colocalization of CTCF and Rad21 binding at ~60 sites throughout the V(H) region and 2 other sites within the Igh locus. These numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement. To test whether CTCF was involved in locus compaction, we used 3D-FISH to measure compaction in pro-B cells transduced with CTCF shRNA retroviruses. Reduction of CTCF binding resulted in a decrease in Igh locus compaction. Long-range interactions within the Igh locus were measured with the chromosomal conformation capture assay, revealing direct interactions between CTCF sites 5' of DFL16 and the 3' regulatory region, and also the intronic enhancer (Eμ), creating a D(H)-J(H)-Eμ-C(H) domain. Knockdown of CTCF also resulted in the increase of antisense transcription throughout the D(H) region and parts of the V(H) locus, suggesting a widespread regulatory role for CTCF. Together, our findings demonstrate that CTCF plays an important role in the 3D structure of the Igh locus and in the regulation of antisense germline transcription and that it contributes to the compaction of the Igh locus. PMID:21606361

  9. Transcriptome and allele specificity associated with a 3BL locus for Fusarium crown rot resistance in bread wheat.

    PubMed

    Ma, Jian; Stiller, Jiri; Zhao, Qiang; Feng, Qi; Cavanagh, Colin; Wang, Penghao; Gardiner, Donald; Choulet, Frédéric; Feuillet, Catherine; Zheng, You-Liang; Wei, Yuming; Yan, Guijun; Han, Bin; Manners, John M; Liu, Chunji

    2014-01-01

    Fusarium pathogens cause two major diseases in cereals, Fusarium crown rot (FCR) and head blight (FHB). A large-effect locus conferring resistance to FCR disease was previously located to chromosome arm 3BL (designated as Qcrs-3B) and several independent sets of near isogenic lines (NILs) have been developed for this locus. In this study, five sets of the NILs were used to examine transcriptional changes associated with the Qcrs-3B locus and to identify genes linked to the resistance locus as a step towards the isolation of the causative gene(s). Of the differentially expressed genes (DEGs) detected between the NILs, 12.7% was located on the single chromosome 3B. Of the expressed genes containing SNP (SNP-EGs) detected, 23.5% was mapped to this chromosome. Several of the DEGs and SNP-EGs are known to be involved in host-pathogen interactions, and a large number of the DEGs were among those detected for FHB in previous studies. Of the DEGs detected, 22 were mapped in the Qcrs-3B interval and they included eight which were detected in the resistant isolines only. The enrichment of DEG, and not necessarily those containing SNPs between the resistant and susceptible isolines, around the Qcrs-3B locus is suggestive of local regulation of this region by the resistance allele. Functions for 13 of these DEGs are known. Of the SNP-EGs, 28 were mapped in the Qcrs-3B interval and biological functions for 16 of them are known. These results provide insights into responses regulated by the 3BL locus and identify a tractable number of target genes for fine mapping and functional testing to identify the causative gene(s) at this QTL. PMID:25405461

  10. Cloning and chromosome localization of the mouse Ews gene

    SciTech Connect

    Plougastel, B.; Thomas, G.; Delattre, O.; Mattei, M.G.

    1994-09-01

    The human EWS gene encodes a putative RNA binding protein. As a result of acquired chromosome rearrangement, the N-terminal portion of the EWS protein is fused to the DNA binding domain of either FLI1-or ERG in the Ewing family of tumors and to the DNA binding domain of ATF1 in malignant melanoma of soft parts. We have determined the cDNA sequence of the mouse Ews gene. Its nucleotide sequence and its translation product demonstrate 93 and 98% homology with the human EWS cDNA and protein, respectively. The murine Ews locus lies within a conserved synteny segment between human chromosome 22q12 and mouse chromosome 11A1-A3.

  11. Capturing Chromosome Conformation

    NASA Astrophysics Data System (ADS)

    Dekker, Job; Rippe, Karsten; Dekker, Martijn; Kleckner, Nancy

    2002-02-01

    We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This methodology can be applied to the spatial organization of entire genomes in organisms from bacteria to human. Using the yeast Saccharomyces cerevisiae, we could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis. We also analyzed yeast chromosome III at the G1 stage of the cell cycle. We found that chromatin is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich domains were found to exhibit different conformations, and a population-average 3D model of chromosome III could be determined. Chromosome III emerges as a contorted ring.

  12. Different Foreign Genes Incidentally Integrated into the Same Locus of the Streptococcus suis Genome

    PubMed Central

    Sekizaki, Tsutomu; Takamatsu, Daisuke; Osaki, Makoto; Shimoji, Yoshihiro

    2005-01-01

    Some strains of Streptococcus suis possess a type II restriction-modification (RM) system, whose genes are thought to be inserted into the genome between purH and purD from a foreign source by illegitimate recombination. In this study, we characterized the purHD locus of the S. suis genomes of 28 serotype reference strains by DNA sequencing. Four strains contained the RM genes in the locus, as described before, whereas 11 strains possessed other genetic regions of seven classes. The genetic regions contained a single gene or multiple genes that were either unknown or similar to hypothetical genes of other bacteria. The mutually exclusive localization of the genetic regions with the atypical G+C contents indicated that these regions were also acquired from foreign sources. No transposable element or long-repeat sequence was found in the neighboring regions. An alignment of the nucleotide sequences, including the RM gene regions, suggested that the foreign regions were integrated by illegitimate recombination via short stretches of nucleotide identity. By using a thermosensitive suicide plasmid, the RM genes were experimentally introduced into an S. suis strain that did not contain any foreign genes in that locus. Integration of the plasmid into the S. suis genome did not occur in the purHD locus but occurred at various chromosomal loci, where there were 2 to 10 bp of nucleotide identity between the chromosome and the plasmid. These results suggest that various foreign genes described here were incidentally integrated into the same locus of the S. suis genome. PMID:15659665

  13. Genetic heterogeneity of gingival fibromatosis on chromosome 2p

    PubMed Central

    Shashi, V.; Pallos, D.; Pettenati, M.; Cortelli, J.; Fryns, J.; von Kap-Herr, C.; Hart, T.

    1999-01-01

    Gingival fibromatosis (GF) occurs in several genetic forms as a simple Mendelian trait, in malformation syndromes, and in some chromosomal disorders. Specific genes responsible for GF have not been identified. An autosomal dominant form of hereditary gingival fibromatosis (HGF, MIM 135300) was recently mapped to chromosome 2p21 in a large Brazilian family and there was an earlier report of GF in a boy with a cytogenetic duplication involving 2p13→p21. We thus hypothesised that a common gene locus may be responsible for GF in both the Brazilian family and the boy with the chromosome 2p duplication. We performed additional genetic linkage studies on the Brazilian family and molecular cytogenetic studies on the patient with the cytogenetic duplication to correlate more precisely the genetic interval of the HGF phenotype with the duplicated 2p interval. Additional linkage analysis of new family members resulted in refinement of the candidate region for HGF to an 8 Mb region. Molecular cytogenetic analysis of the 2p13→p21 duplication associated with GF showed that the duplicated region was proximal to the candidate interval for HGF. Thus, our results support the presence of two different gene loci on chromosome 2p that are involved in GF.


Keywords: gingival fibromatosis; chromosome duplication; chromosome 2 PMID:10507724

  14. Global identification of yeast chromosome interactions using Genome conformation capture.

    PubMed

    Rodley, C D M; Bertels, F; Jones, B; O'Sullivan, J M

    2009-11-01

    The association of chromosomes with each other and other nuclear components plays a critical role in nuclear organization and Genome function. Here, using a novel and generally applicable methodology (Genome conformation capture [GCC]), we reveal the network of chromosome interactions for the yeast Saccharomyces cerevisiae. Inter- and intra-chromosomal interactions are non-random and the number of interactions per open reading frame depends upon the dispensability of the gene product. Chromosomal interfaces are organized and provide evidence of folding within chromosomes. Interestingly, the genomic connections also involve the 2 microm plasmid and the mitochondrial genome. Mitochondrial interaction partners include genes of alpha-proteobacterial origin and the ribosomal DNA. Organization of the 2 microm plasmid aligns two inverted repeats (IR1 and IR2) and displays the stability locus on a prominent loop thus making it available for plasmid clustering. Our results form the first global map of chromosomal interactions in a eukaryotic nucleus and demonstrate the highly connected nature of the yeast genome. These results have significant implications for understanding eukaryotic genome organization.

  15. The use of a mutationally unstable X-chromosome in Drosophila melanogaster for mutagenicity testing.

    PubMed

    Rasmuson, B; Svahlin, H; Rasmuson, A; Montell, I; Olofsson, H

    1978-08-01

    Somatic eye-colour mutations in an unstable genetic system, caused by a transposable element in the white locus of the X-chromosome in Drosophila melanogaster, is suggested as an assay system for mutagenicity testing. The system is evaluated by comparison with a corresponding system in a stable X-chromosome. Its sensitivity is confirmed with X-ray and EMS treatment, and it is found to be confined to the specific segment of the X-chromosome where the transposable element is localized. PMID:97525

  16. Y chromosomal DNA variation and the peopling of Japan.

    PubMed Central

    Hammer, M F; Horai, S

    1995-01-01

    Four loci mapping to the nonrecombining portion of the Y chromosome were genotyped in Japanese populations from Okinawa, the southernmost island of Japan; Shizuoka and Aomori on the main island of Honshu; and a small sample of Taiwanese. The Y Alu polymorphic (YAP) element is present in 42% of the Japanese and absent in the Taiwanese, confirming the irregular distribution of this polymorphism in Asia. Data from the four loci were used to determine genetic distances among populations, construct Y chromosome haplotypes, and estimate the degree of genetic diversity in each population and on different Y chromosome haplotypes. Evolutionary analysis of Y haplotypes suggests that polymorphisms at the YAP (DYS287) and DXYS5Y loci originated a single time, whereas restriction patterns at the DYS1 locus and microsatellite alleles at the DYS19 locus arose more than once. Genetic distance analysis indicated that the Okinawans are differentiated from Japanese living on Honshu. The data support the hypotheses that modern Japanese populations have resulted from distinctive genetic contributions involving the ancient Jomon people and Yayoi immigrants from Korea or mainland China, with Okinawans experiencing the least amount of admixture with the Yayoi. It is suggested that YAP+ chromosomes migrated to Japan with the Jomon people > 10,000 years ago and that a large infusion of YAP- chromosomes entered Japan with the Yayoi migration starting 2,300 years ago. Different degrees of genetic diversity carried by these two ancient chromosomal lineages may be explained by the different life-styles (hunter-gatherer versus agriculturalist). of the migrant groups, the size of the founding populations, and the antiquities of the founding events. Images Figure 1 PMID:7717406

  17. The X factor: X chromosome dosage compensation in the evolutionarily divergent monotremes and marsupials.

    PubMed

    Whitworth, Deanne J; Pask, Andrew J

    2016-08-01

    Marsupials and monotremes represent evolutionarily divergent lineages from the majority of extant mammals which are eutherian, or placental, mammals. Monotremes possess multiple X and Y chromosomes that appear to have arisen independently of eutherian and marsupial sex chromosomes. Dosage compensation of X-linked genes occurs in monotremes on a gene-by-gene basis, rather than through chromosome-wide silencing, as is the case in eutherians and marsupials. Specifically, studies in the platypus have shown that for any given X-linked gene, a specific proportion of nuclei within a cell population will silence one locus, with the percentage of cells undergoing inactivation at that locus being highly gene-specific. Hence, it is perhaps not surprising that the expression level of X-linked genes in female platypus is almost double that in males. This is in contrast to the situation in marsupials where one of the two X chromosomes is inactivated in females by the long non-coding RNA RSX, a functional analogue of the eutherian XIST. However, marsupial X chromosome inactivation differs from that seen in eutherians in that it is exclusively the paternal X chromosome that is silenced. In addition, marsupials appear to have globally upregulated X-linked gene expression in both sexes, thus balancing their expression levels with those of the autosomes, a process initially proposed by Ohno in 1967 as being a fundamental component of the X chromosome dosage compensation mechanism but which may not have evolved in eutherians.

  18. The X factor: X chromosome dosage compensation in the evolutionarily divergent monotremes and marsupials.

    PubMed

    Whitworth, Deanne J; Pask, Andrew J

    2016-08-01

    Marsupials and monotremes represent evolutionarily divergent lineages from the majority of extant mammals which are eutherian, or placental, mammals. Monotremes possess multiple X and Y chromosomes that appear to have arisen independently of eutherian and marsupial sex chromosomes. Dosage compensation of X-linked genes occurs in monotremes on a gene-by-gene basis, rather than through chromosome-wide silencing, as is the case in eutherians and marsupials. Specifically, studies in the platypus have shown that for any given X-linked gene, a specific proportion of nuclei within a cell population will silence one locus, with the percentage of cells undergoing inactivation at that locus being highly gene-specific. Hence, it is perhaps not surprising that the expression level of X-linked genes in female platypus is almost double that in males. This is in contrast to the situation in marsupials where one of the two X chromosomes is inactivated in females by the long non-coding RNA RSX, a functional analogue of the eutherian XIST. However, marsupial X chromosome inactivation differs from that seen in eutherians in that it is exclusively the paternal X chromosome that is silenced. In addition, marsupials appear to have globally upregulated X-linked gene expression in both sexes, thus balancing their expression levels with those of the autosomes, a process initially proposed by Ohno in 1967 as being a fundamental component of the X chromosome dosage compensation mechanism but which may not have evolved in eutherians. PMID:26806635

  19. Chromosome Fragments in DICTYOSTELIUM DISCOIDEUM Obtained from Parasexual Crosses between Strains of Different Genetic Background

    PubMed Central

    Williams, Keith L.; Robson, Gillian E.; Welker, Dennis L.

    1980-01-01

    The first aneuploid strains of Dictyostelium discoideum have been unambiguously characterized, using cytological and genetic analysis. Three independently isolated, but genetically similar, fragment chromosomes have been observed in segregants from diploids formed between haploid strains derived from the NC4 and V12 isolates of D. discoideum. Once generated, the fragment chromosomes, all of which have V12-derived centromeres, can be maintained in a NC4 genetic background. Genetic evidence is consistent with the view that all three fragment chromosomes studied encompass the region from the centromere to the whiA locus of linkage group II and terminate in the interval between whiA and acrA. From cytological studies, one of the fragment chromosomes consists of approximately half of linkage group II.—We observed no deleterious effect on viability or asexual fruiting-body formation in either haploid or diploid strains carrying an additional incomplete chromosome and hence are disomic or trisomic, respectively, for part of linkage group II. The incomplete chromosome is lost at a frequency of 2 to 3% from disomic and trisomic strains, but surprisingly this loss is not increased in the presence of the haploidizing agent, benlate. A new locus (clyA), whose phenotype is altered colony morphology, is assigned to the region of linkage group II encompassed by the fragment chromosome. PMID:17249037

  20. Human chromosome 22.

    PubMed Central

    Kaplan, J C; Aurias, A; Julier, C; Prieur, M; Szajnert, M F

    1987-01-01

    The acrocentric chromosome 22, one of the shortest human chromosomes, carries about 52 000 kb of DNA. The short arm is made up essentially of heterochromatin and, as in other acrocentric chromosomes, it contains ribosomal RNA genes. Ten identified genes have been assigned to the long arm, of which four have already been cloned and documented (the cluster of lambda immunoglobulin genes, myoglobin, the proto-oncogene c-sis, bcr). In addition, about 10 anonymous DNA segments have been cloned from chromosome 22 specific DNA libraries. About a dozen diseases, including at least four different malignancies, are related to an inherited or acquired pathology of chromosome 22. They have been characterised at the phenotypic or chromosome level or both. In chronic myelogenous leukaemia, with the Ph1 chromosome, and Burkitt's lymphoma, with the t(8;22) variant translocation, the molecular pathology is being studied at the DNA level, bridging for the first time the gap between cytogenetics and molecular genetics. PMID:3550088

  1. Sequential cloning of chromosomes

    DOEpatents

    Lacks, Sanford A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism's chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  2. Sequential cloning of chromosomes

    DOEpatents

    Lacks, S.A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

  3. Sequential cloning of chromosomes

    SciTech Connect

    Lacks, S.A.

    1991-12-31

    A method for sequential cloning of chromosomal DNA and chromosomal DNA cloned by this method are disclosed. The method includes the selection of a target organism having a segment of chromosomal DNA to be sequentially cloned. A first DNA segment, having a first restriction enzyme site on either side. homologous to the chromosomal DNA to be sequentially cloned is isolated. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

  4. CHROMOSOMES OF AMERICAN MARSUPIALS.

    PubMed

    BIGGERS, J D; FRITZ, H I; HARE, W C; MCFEELY, R A

    1965-06-18

    Studies of the chromosomes of four American marsupials demonstrated that Caluromys derbianus and Marmosa mexicana have a diploid number of 14 chromosomes, and that Philander opossum and Didelphis marsupialis have a diploid number of 22. The karyotypes of C. derbianus and M. mexicana are similar, whereas those of P. opossum and D. marsupialis are dissimilar. If the 14-chromosome karyotype represents a reduction from a primitive number of 22, these observations suggest that the change has occurred independently in the American and Australasian forms.

  5. A new chromosome was born: comparative chromosome painting in Boechera.

    PubMed

    Koch, Marcus A

    2015-09-01

    Comparative chromosome painting is a powerful tool to study the evolution of chromosomes and genomes. Analyzing karyotype evolution in cruciferous plants highlights the origin of aberrant chromosomes in apomictic Boechera and further establishes the cruciferous plants as important model system for our understanding of plant chromosome and genome evolution. PMID:26228436

  6. Molecular analysis of chromosomal rearrangements using pulsed field gel electrophoresis and somatic cell hybrids

    SciTech Connect

    Davis, L.M. )

    1991-01-01

    Many human genetic diseases, including some cancers, are characterized by consistent chromosome abnormalities, such as deletions and translocations. Analyses of these mutations often prove crucial to the eventual cloning and characterization of the gene(s) responsible for the disease. Two methods for analyzing these chromosome abnormalities have been developed in recent years: somatic cell hybridization and pulsed field gel electrophoresis (PFGE). Somatic cell hybridization is a technique for segregating an aberrant chromosome from its normal homologue in a cell derived from an unrelated species, which is usually a rodent. Demonstrations of these analytic techniques are presented, using as an example chromosomal abnormalities involving human chromosome band 11p13, the locus for the Wilms' tumor, aniridia, genitourinary abnormality, and mental retardation (WAGR) syndrome.

  7. Origin of human chromosome 2: An ancestral telomere-telomere fusion

    SciTech Connect

    Ijdo, J.W.; Baldini, A.; Ward, D.C.; Reeders, S.T.; Wells, R.A. )

    1991-10-15

    The authors identified two allelic genomic cosmids from human chromosome 2, c8.1 and c29B, each containing two inverted arrays of the vertebrate telomeric repeat in a head-to-head arrangement, 5{prime}(TTAGGG){sub n}-(CCCTAA){sub m}3{prime}. Sequences flanking this telomeric repeat are characteristic of present-day human pretelomeres. BAL-31 nuclease experiments with yeast artificial chromosome clones of human telomeres and fluorescence in situ hybridization reveal that sequences flanking these inverted repeats hybridize both to band 2q13 and to different, but overlapping, subsets of human chromosome ends. They conclude that the locus cloned in cosmids c8.1 and c29B is the relic of an ancient telomere-telomere fusion and marks the point at which two ancestral ape chromosomes fused to give rise to human chromosome 2.

  8. A mutable X{sup Z} chromosome isolated from a natural population of Drosophila melanogaster

    SciTech Connect

    Yurchenko, N.N.; Zakharov, I.K.

    1995-07-01

    In 1986, a mutable X{sup Z} chromosome, in which mutation at genes yellow, white, and singed were recorded, was isolated from a natural population of Drosophila melanogaster from Zaporozh`e. Visible mutations in the region garnet-forked were also detected. Mutations appeared at a rate of about 10{sup {minus}4} and were probably postmeiotic. Cytological analysis showed that two types of inversions occurred independently in X{sup Z} chromosome. Specific features of this chromosome are hypermutability of the white locus (the mutation rate was approximately 10{sup {minus}3}) and a hot spot for chromosomal rearrangements in the terminal segment of the X chromosome. 9 refs., 2 figs., 2 tabs.

  9. Identification of the origin of marker chromosomes by two-color fluorescence in situ hybridization and polymerase chain reaction in azoospermic patients.

    PubMed

    Wei, C L; Cheng, J L; Yang, W C; Li, L Y; Cheng, H C; Fu, J J

    2015-11-19

    Y chromosomal microdeletions at the azoospermia factor locus and chromosome abnormalities have been implicated as the major causes of idiopathic male infertility. A marker chromosome is a structurally abnormal chromosome in which no part can be identified by cytogenetics. In this study, to identify the origin of the marker chromosomes and to perform a genetic diagnosis of patients with azoospermia, two-color fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) techniques were carried out. The marker chromosomes for the two patients with azoospermia originated in the Y chromosome; it was ascertained that the karyotype of both patients was 46,X, ish del(Y)(q11)(DYZ3+, DXZ1-). The combination of two-color FISH and PCR techniques is an important method for the identification of the origin of marker chromosomes. Thus, genetic counseling and a clear genetic diagnosis of patients with azoospermia before intracytoplasmic sperm injection or other clinical managements are important.

  10. Excision of the Shigella Resistance Locus Pathogenicity Island in Shigella flexneri Is Stimulated by a Member of a New Subgroup of Recombination Directionality Factors

    PubMed Central

    Luck, Shelley N.; Turner, Sally A.; Rajakumar, Kumar; Adler, Ben; Sakellaris, Harry

    2004-01-01

    Pathogenicity islands are capable of excision and insertion within bacterial chromosomes. We describe a protein, Rox, that stimulates excision of the Shigella resistance locus pathogenicity island in Shigella flexneri. Sequence analysis suggests that Rox belongs to a new subfamily of recombination directionality factors, which includes proteins from P4, enterohemorrhagic Escherichia coli, and Yersinia pestis. PMID:15292162

  11. X Chromosome Control of Meiotic Chromosome Synapsis in Mouse Inter-Subspecific Hybrids

    PubMed Central

    Bhattacharyya, Tanmoy; Reifova, Radka; Gregorova, Sona; Simecek, Petr; Gergelits, Vaclav; Mistrik, Martin; Martincova, Iva; Pialek, Jaroslav; Forejt, Jiri

    2014-01-01

    Hybrid sterility (HS) belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi. Although hybrid sterility occurs almost universally among animal and plant species, most of our current knowledge comes from the classical genetic studies on Drosophila interspecific crosses or introgressions. With the house mouse subspecies Mus m. musculus and Mus m. domesticus as a model, new research tools have become available for studies of the molecular mechanisms and genetic networks underlying HS. Here we used QTL analysis and intersubspecific chromosome substitution strains to identify a 4.7 Mb critical region on Chromosome X (Chr X) harboring the Hstx2 HS locus, which causes asymmetrical spermatogenic arrest in reciprocal intersubspecific F1 hybrids. Subsequently, we mapped autosomal loci on Chrs 3, 9 and 13 that can abolish this asymmetry. Combination of immunofluorescent visualization of the proteins of synaptonemal complexes with whole-chromosome DNA FISH on pachytene spreads revealed that heterosubspecific, unlike consubspecific, homologous chromosomes are predisposed to asynapsis in F1 hybrid male and female meiosis. The asynapsis is under the trans- control of Hstx2 and Hst1/Prdm9 hybrid sterility genes in pachynemas of male but not female hybrids. The finding concurred with the fertility of intersubpecific F1 hybrid females homozygous for the Hstx2Mmm allele and resolved the apparent conflict with the dominance theory of Haldane's rule. We propose that meiotic asynapsis in intersubspecific hybrids is a consequence of cis-acting mismatch between homologous chromosomes modulated by the trans-acting Hstx2 and Prdm9 hybrid male sterility genes. PMID:24516397

  12. X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids.

    PubMed

    Bhattacharyya, Tanmoy; Reifova, Radka; Gregorova, Sona; Simecek, Petr; Gergelits, Vaclav; Mistrik, Martin; Martincova, Iva; Pialek, Jaroslav; Forejt, Jiri

    2014-02-01

    Hybrid sterility (HS) belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi. Although hybrid sterility occurs almost universally among animal and plant species, most of our current knowledge comes from the classical genetic studies on Drosophila interspecific crosses or introgressions. With the house mouse subspecies Mus m. musculus and Mus m. domesticus as a model, new research tools have become available for studies of the molecular mechanisms and genetic networks underlying HS. Here we used QTL analysis and intersubspecific chromosome substitution strains to identify a 4.7 Mb critical region on Chromosome X (Chr X) harboring the Hstx2 HS locus, which causes asymmetrical spermatogenic arrest in reciprocal intersubspecific F1 hybrids. Subsequently, we mapped autosomal loci on Chrs 3, 9 and 13 that can abolish this asymmetry. Combination of immunofluorescent visualization of the proteins of synaptonemal complexes with whole-chromosome DNA FISH on pachytene spreads revealed that heterosubspecific, unlike consubspecific, homologous chromosomes are predisposed to asynapsis in F1 hybrid male and female meiosis. The asynapsis is under the trans- control of Hstx2 and Hst1/Prdm9 hybrid sterility genes in pachynemas of male but not female hybrids. The finding concurred with the fertility of intersubpecific F1 hybrid females homozygous for the Hstx2(Mmm) allele and resolved the apparent conflict with the dominance theory of Haldane's rule. We propose that meiotic asynapsis in intersubspecific hybrids is a consequence of cis-acting mismatch between homologous chromosomes modulated by the trans-acting Hstx2 and Prdm9 hybrid male sterility genes. PMID:24516397

  13. Chromosome doubling method

    DOEpatents

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  14. Evidence for a susceptibility locus for manic-depressive disorder in Xq26

    SciTech Connect

    Pekkarinen, P.; Bredbacka, P.E.; Terwilliger, J.

    1994-09-01

    Manic-depression (MD) is a severe psychiatric disorder affecting 1% of the population. Several linkage studies have provided evidence for a susceptibility locus for MD in chromosome Xq27-28. However, validity of these findings have remained unclear for several reasons: linkage has been suggested to two distinct chromosomal regions (F9 and CB-G6PD) separated by 30 cM, linkage has been found in only few of the pedigrees analyzed and ascertainment bias have probably been introduced when using classical markers like CB. The aim of our study was to analyze several markers expanding both of these regions in one extended Finnish pedigree with 13 affected individuals (bipolar or schizoaffective disorder) and without male-to-male transmission. Together 27 polymorphic X chromosomal markers were studied, 22 of them in Xq25-q28. Linkage analyses were carried out using a dominant model, 0.005 disease gene frequency, age-dependent penetrance with a maximum penetrance of 0.80 and low phenocopy rate. Two-point linkage analyses resulted in clearly negative lod scores (<-2) to almost all markers outside the chromosomal region of Xq26. Three markers DXS458, GABRA3 and G6PD, gave uninformative lod scores but respective chromosomal areas could be excluded by other markers in the vicinity. Opposite to this, several markers on Xq26 resulted in positive lod scores. A maximum lod score of 3.4 was obtained with the marker AFM205wd2 at {theta}=0.0. This marker is located about 7 cM centromeric to F9. When all published linkage data on Xq26-q28 was reanalyzed no evidence for locus heterogeneity emerged suggesting a more general significance of this DNA region in the predisposition to manic-depressive disorder.

  15. Polymorphic DNA haplotypes at the phenylalanine hydroxylase (PAH) locus in Asian families with phenylketonuria (PKU).

    PubMed

    Daiger, S P; Reed, L; Huang, S S; Zeng, Y T; Wang, T; Lo, W H; Okano, Y; Hase, Y; Fukuda, Y; Oura, T

    1989-08-01

    DNA polymorphisms at the phenylalanine hydroxylase (PAH) locus have proved highly effective in linkage diagnosis of phenylketonuria (PKU) in Caucasian families. More than 10 RFLP sites have been reported within the PAH structural locus in Caucasians. With information from affected and unaffected offspring in PKU families it is often possible to reconstruct complete RFLP haplotypes in parents and to use these haplotypes to follow the segregation of PKU within families and to determine the distribution of PKU chromosomes within populations. To establish the utility of these RFLPs in characterizing Asian families with PKU, we typed eight DNA sites in 21 Chinese families and 12 Japanese families with classical PKU. The eight RFLPs were chosen for their informativeness in Caucasians. From these families we reconstructed a total of 91 complete PAH haplotypes, 44 from non-PKU chromosomes and 47 from PKU-bearing chromosomes. Although all eight marker sites are polymorphic in both Chinese and Japanese, there is much less haplotypic variation in Asians than in Caucasians. In particular, one haplotype alone, haplotype 4, accounts for more than 77% of non-PKU chromosomes and for more than 80% of PKU-bearing chromosomes. Haplotype 4 is also relatively common in Caucasians. The next most common Asian haplotype is 10 times less frequent than haplotype 4. By contrast, in many Caucasian populations the sum of the frequencies of the five most common haplotypes is still less than 80%, and several of the most common haplotypes are equally frequent. Even though the extent of haplotypic variation in Asians is severely limited, the few haplotypes that are found often differ at a number of RFLP sites.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. 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

  17. A survey of EMS-induced biennial Beta vulgaris mutants reveals a novel bolting locus which is unlinked to the bolting gene B.

    PubMed

    Büttner, Bianca; Abou-Elwafa, Salah F; Zhang, Wenying; Jung, Christian; Müller, Andreas E

    2010-10-01

    Beta vulgaris is a facultative perennial species which exhibits large intraspecific variation in vernalization requirement and includes cultivated biennial forms such as the sugar beet. Vernalization requirement is under the genetic control of the bolting locus B on chromosome II. Previously, ethyl methanesulfonate (EMS) mutagenesis of an annual accession had yielded several mutants which require vernalization to bolt and behave as biennials. Here, five F2 populations derived from crosses between biennial mutants and annual beets were tested for co-segregation of bolting phenotypes with genotypic markers located at the B locus. One mutant appears to be mutated at the B locus, suggesting that an EMS-induced mutation of B can be sufficient to abolish annual bolting. Co-segregation analysis in four populations indicates that the genetic control of bolting also involves previously unknown major loci not linked to B, one of which also affects bolting time and was genetically mapped to chromosome IX.

  18. Micromechanics of human mitotic chromosomes

    NASA Astrophysics Data System (ADS)

    Sun, Mingxuan; Kawamura, Ryo; Marko, John F.

    2011-02-01

    Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed.

  19. A New Map Location for the ilvB Locus of ESCHERICHIA COLI

    PubMed Central

    Newman, Thomas C.; Levinthal, Mark

    1980-01-01

    We isolated, in E. coli K12, new alleles of the ilvB locus, the structural gene for acetolactate synthase isoenzyme I, and showed them to map at or near the ilvB619 site. The map position of the ilvB locus was redetermined because plasmids containing the ilvC-cya portion of the chromosome did not complement mutations at the ilvB locus. Furthermore, diploids for the ilvEDAC genes formed with these plasmids in an ilvHI background facilitated the isolation of the new ilvB alleles. The ilvB locus was remapped and found to be located at 81.5 minutes, between the uhp and dnaA loci. This location was determined by two- and three-point transductional crosses, deletion mapping and complementation with newly isolated plasmids. One of the new alleles of the ilvB gene is a mu-1 insertion. When present in the donor strain, this allele interferes with the linkage of genes flanking the mu-1 insertion, as well as the linkage of genes to either side of the mu-1 insertion. PMID:7009323

  20. Dissection of the locus control function located on the chicken lysozyme gene domain in transgenic mice.

    PubMed Central

    Bonifer, C; Yannoutsos, N; Krüger, G; Grosveld, F; Sippel, A E

    1994-01-01

    The entire chicken lysozyme gene locus including all known cis-regulatory sequences and the 5' and 3' matrix attachment sites defining the borders of the DNase I sensitive chromatin domain, is expressed at a high level and independent of its chromosomal position in macrophages of transgenic mice. It was concluded that the lysozyme gene locus carries a locus control function. We analysed several cis-regulatory deletion mutants to investigate their influence on tissue specificity and level of expression. Position independent expression of the gene is lost whenever one of the upstream tissue specific enhancer regions is deleted, although tissue specific expression is usually retained. Deletion of the domain border fragments has no influence on copy number dependency of expression. However, without these regions an increased incidence of ectopic expression is observed. This suggests that the domain border fragments may help to suppress transgene expression in inappropriate tissues. We conclude, that position independent expression of the lysozyme gene is not controlled by a single specific region of the locus but is the result of the concerted action of several tissue specific upstream regulatory DNA elements with the promoter. Images PMID:7937146

  1. The role of the hok/sok locus in bacterial response to stressful growth conditions.

    PubMed

    Chukwudi, Chinwe U; Good, Liam

    2015-02-01

    The hok/sok locus is renowned for its plasmid stabilization effect via post-segregational killing of plasmid-free daughter cells. However, the function(s) of the chromosome-encoded loci, which are more abundant in pathogenic strains of a broad range of enteric bacteria, are yet to be understood. Also, the frequent occurrence of this toxin/antitoxin addiction system in multi-drug resistance plasmids suggests additional roles. In this study, the effects of the hok/sok locus on the growth of bacteria in stressful growth-limiting conditions such as high temperature and antibiotic burden were investigated using hok/sok plasmids. The results showed that the hok/sok locus prolonged the lag phase of host cell cultures, thereby enabling the cells to adapt, respond to the stress and eventually thrive in these growth-limiting conditions by increasing the growth rate at exponential phase. The hok/sok locus also enhanced the survival and growth of cells in low cell density cultures irrespective of unfavourable growth conditions, and may complement existing or defective SOS mechanism. In addition to the plasmid stabilization function, these effects would enhance the ability of pathogenic bacteria to establish infections and propagate the antibiotic resistance elements carried on these plasmids, thereby contributing to the virulence of such bacteria.

  2. Segregation of recessive phenotypes in somatic cell hybrids role of mitotic recombination, gene inactivation, and chromosome nondisjunction

    SciTech Connect

    Campbell, C.E.; Worton, R.G.

    1981-04-01

    Somatic cell hybrids heterozygous at the emetine resistance locus (emt/sup r//emt/sup +/) or the chromate resistance locus (chr/sup r//chr/sup +/) are known to segregate the recessive drug resistance phenotype at high frequency. The authors have examined mechanisms of segregation in Chinese hamster cell hybrids heterozygous at these two loci, both of which map to the long arm of Chinese hamster chromosome 2. To allow the fate of chromosomal arms through the segregation process, our hybrids were also heterozygous at the mtx (methotrexate resistance) locus on the short arm of chromosome 2 and carried cytogenetically marked chromosomes with either a short-arm deletion 2p/sup -/) or a long-arm addition (2q/sup +/). Karotype and phenotype analysis of emetine- or chromate-resistant segregants from such hybrids allowed us to distinguish four potential segregation mechanisms: (i) loss of the emt/sup +/ - or chr/sup +/-bearing chromosome; (ii) mitotic recombination between the centromere and the emt or chr loci giving rise to homozygous resistant segregants; (iii) inactivation of the emt/sup +/ or chr/sup +/ alleles; and (iv) loss of the emt/sup +/ - or chr/sup +/-bearing chromosome with duplication of the homologous chromosome carrying the emt/sup r/ or chr/sup r/ allele. Of 48 independent segregants examined, only 9 (20%) arose by simple chromosome loss. Two segregants (4%) were consistent with a gene inactivation mechanism, but because of their rarity, other mechanisms such as mutation or submicroscopic deletion could not be excluded. Twenty-one segregants (44%) arose by either mitotic recombination or chromosome loss and duplication; the two mechanisms were not distinguishable in that experiment. Finally, in hybrids allowing these two mechanisms to be distinguished, 15 segregants (31%) arose by chromosome loss and duplication, and none arose by mitotic recombination.

  3. Identification and application of additional restriction fragment length polymorphisms at the human ornithine transcarbamylase locus.

    PubMed

    Fox, J E; Hack, A M; Fenton, W A; Rosenberg, L E

    1986-06-01

    Two additional restriction fragment length polymorphisms (RFLPs) have been identified at the human ornithine transcarbamylase (OTC) locus. Approximately 11% of women are heterozygous for an RFLP characterized by polymorphic bands at 3.7 and 3.6 kilobasepairs (kbp) observed after DNA digestion with TaqI. Twenty-nine percent of women are heterozygous for an RFLP characterized by polymorphic bands at 18.0 and 5.2 kbp observed after digestion with BamHI. Thus, in combination with the previously reported RFLPs identified using MspI, the X chromosomes in approximately 80% of women at risk for having a son with OTC deficiency are distinguishable by RFLPs at the OTC locus. Furthermore, we show that these RFLPs will be useful in families for prenatal diagnosis of OTC deficiency, carrier detection, and carrier exclusion.

  4. Allelic association at the D14S43 locus in early onset Alzheimer`s disease

    SciTech Connect

    Brice, A.; Tardieu, S.; Campion, D.; Martinez, M.

    1995-04-24

    The D14S43 marker is closely linked to the major gene for early onset autosomal dominant Alzheimer`s disease on chromosome 14. Allelic frequencies at the D14S43 locus were compared in 113 familial and isolated cases of early onset Alzheimer`s disease (<60 years of age at onset) (EOAD) and 109 unaffected individuals of the same geographic origin. Allele 7 was significantly (P = 0.033) more frequent in type 1 EOAD patients (13.2%), defined by the presence of at least another first degree relative with EOAD, than in controls (4.1%). Since an autosomal dominant gene is probably responsible for type 1 patients, allelic association may reflect linkage disequilibrium at the D14S43 locus. This would mean that some patients share a common ancestral mutation. However, since multiple tests were carried out, this result must be interpreted with caution, and needs confirmation in an independent sample. 16 refs., 2 tabs.

  5. Significance of linkage disequilibrium between the fragile X locus and its flanking markers

    SciTech Connect

    Chiurazzi, P.; Neri, G.; Macpherson, J.

    1996-07-12

    The identification of several microsatellite markers flanking the FRAXA locus was instrumental in the positional cloning of the FMR1 gene. These markers can still be valuable in family studies, e.g., as additional evidence in prenatal diagnosis. Additionally, they were employed to verify the presence of any significant gametic disequilibrium between the fragile X mutation and some haplotypes, although the high mutation rate predicted from early segregation studies implied that new mutants would arise on almost every chromosomal background. Thus, the discovery of linkage disequilibrium encompassing the fragile X locus has been surprising. Here, we review the available evidence of such gametic association and underline its implications for the mutational mechanism. 50 refs., 1 fig., 2 tabs.

  6. Familial cutaneous malignant melanoma: autosomal dominant trait possibly linked to the Rh locus.

    PubMed Central

    Greene, M H; Goldin, L R; Clark, W H; Lovrien, E; Kraemer, K H; Tucker, M A; Elder, D E; Fraser, M C; Rowe, S

    1983-01-01

    Segregation and linkage analyses were undertaken in families with multiple cases of cutaneous malignant melanoma (CMM) and a recently-described melanoma precursor, the dysplastic nevus syndrome (DNS). Clinical and laboratory data, including 23 genetic markers, were collected on 401 members of 14 high-risk kindreds. Pedigree analysis was compatible with an autosomal dominant mode of inheritance for the familial CMM trait. Although a similar model probably applies to the DNS trait as well, segregation analysis could not confirm the presence of a major locus. However, linkage analysis suggested that an autosomal dominant model was appropriate for the DNS, and that a DNS/CMM susceptibility gene may be located on the short arm of chromosome 1, within 30 map units of the Rh locus [maximum logarithm of odds (lod) score = 2.00]. Images PMID:6577466

  7. Variation at the fragile X locus does not influence susceptibility to bipolar disorder

    SciTech Connect

    Craddock, N.; Daniels, J.; McGuffin, P.

    1994-06-15

    Over the last 20 years several pedigrees have been reported which are suggestive of linkage between susceptibility to bipolar disorder and markers on chromosome Xq28. Other workers have failed to replicate these reports and the methodology of the positive reports has been criticized. Recently there have been several reports of an association between fragile X (FRA(X)) and affective disorder within families and in unrelated individuals compared with controls. Such reports could be consistent with the Xq28 marker reports because FRA(X) maps to Xq27.3. We report a study at the FRA(X) CGG repeat locus in 79 unrelated Caucasian bipolar probands without fragile X syndrome and 77 unrelated controls. We found no evidence that variation at this locus confers susceptibility to bipolar disorder. 28 refs., 1 fig.

  8. Mitotic-Chromosome-Based Physical Mapping of the Culex quinquefasciatus Genome

    PubMed Central

    Naumenko, Anastasia N.; Timoshevskiy, Vladimir A.; Kinney, Nicholas A.; Kokhanenko, Alina A.; deBruyn, Becky S.; Lovin, Diane D.; Stegniy, Vladimir N.; Severson, David W.; Sharakhov, Igor V.; Sharakhova, Maria V.

    2015-01-01

    The genome assembly of southern house mosquito Cx. quinquefasciatus is represented by a high number of supercontigs with no order or orientation on the chromosomes. Although cytogenetic maps for the polytene chromosomes of this mosquito have been developed, their utilization for the genome mapping remains difficult because of the low number of high-quality spreads in chromosome preparations. Therefore, a simple and robust mitotic-chromosome-based approach for the genome mapping of Cx. quinquefasciatus still needs to be developed. In this study, we performed physical mapping of 37 genomic supercontigs using fluorescent in situ hybridization on mitotic chromosomes from imaginal discs of 4th instar larvae. The genetic linkage map nomenclature was adopted for the chromosome numbering based on the direct positioning of 58 markers that were previously genetically mapped. The smallest, largest, and intermediate chromosomes were numbered as 1, 2, and 3, respectively. For idiogram development, we analyzed and described in detail the morphology and proportions of the mitotic chromosomes. Chromosomes were subdivided into 19 divisions and 72 bands of four different intensities. These idiograms were used for mapping the genomic supercontigs/genetic markers. We also determined the presence of length polymorphism in the q arm of sex-determining chromosome 1 in Cx. quinquefasciatus related to the size of ribosomal locus. Our physical mapping and previous genetic linkage mapping resulted in the chromosomal assignment of 13% of the total genome assembly to the chromosome bands. We provided the first detailed description, nomenclature, and idiograms for the mitotic chromosomes of Cx. quinquefasciatus. Further application of the approach developed in this study will help to improve the quality of the southern house mosquito genome. PMID:25768920

  9. Mitotic-chromosome-based physical mapping of the Culex quinquefasciatus genome.

    PubMed

    Naumenko, Anastasia N; Timoshevskiy, Vladimir A; Kinney, Nicholas A; Kokhanenko, Alina A; deBruyn, Becky S; Lovin, Diane D; Stegniy, Vladimir N; Severson, David W; Sharakhov, Igor V; Sharakhova, Maria V

    2015-01-01

    The genome assembly of southern house mosquito Cx. quinquefasciatus is represented by a high number of supercontigs with no order or orientation on the chromosomes. Although cytogenetic maps for the polytene chromosomes of this mosquito have been developed, their utilization for the genome mapping remains difficult because of the low number of high-quality spreads in chromosome preparations. Therefore, a simple and robust mitotic-chromosome-based approach for the genome mapping of Cx. quinquefasciatus still needs to be developed. In this study, we performed physical mapping of 37 genomic supercontigs using fluorescent in situ hybridization on mitotic chromosomes from imaginal discs of 4th instar larvae. The genetic linkage map nomenclature was adopted for the chromosome numbering based on the direct positioning of 58 markers that were previously genetically mapped. The smallest, largest, and intermediate chromosomes were numbered as 1, 2, and 3, respectively. For idiogram development, we analyzed and described in detail the morphology and proportions of the mitotic chromosomes. Chromosomes were subdivided into 19 divisions and 72 bands of four different intensities. These idiograms were used for mapping the genomic supercontigs/genetic markers. We also determined the presence of length polymorphism in the q arm of sex-determining chromosome 1 in Cx. quinquefasciatus related to the size of ribosomal locus. Our physical mapping and previous genetic linkage mapping resulted in the chromosomal assignment of 13% of the total genome assembly to the chromosome bands. We provided the first detailed description, nomenclature, and idiograms for the mitotic chromosomes of Cx. quinquefasciatus. Further application of the approach developed in this study will help to improve the quality of the southern house mosquito genome.

  10. Noncoding RNAs and epigenetic mechanisms during X-chromosome inactivation.

    PubMed

    Gendrel, Anne-Valerie; Heard, Edith

    2014-01-01

    In mammals, the process of X-chromosome inactivation ensures equivalent levels of X-linked gene expression between males and females through the silencing of one of the two X chromosomes in female cells. The process is established early in development and is initiated by a unique locus, which produces a long noncoding RNA, Xist. The Xist transcript triggers gene silencing in cis by coating the future inactive X chromosome. It also induces a cascade of chromatin changes, including posttranslational histone modifications and DNA methylation, and leads to the stable repression of all X-linked genes throughout development and adult life. We review here recent progress in our understanding of the molecular mechanisms involved in the initiation of Xist expression, the propagation of the Xist RNA along the chromosome, and the cis-elements and trans-acting factors involved in the maintenance of the repressed state. We also describe the diverse strategies used by nonplacental mammals for X-chromosome dosage compensation and highlight the common features and differences between eutherians and metatherians, in particular regarding the involvement of long noncoding RNAs.

  11. Designed construction of recombinant DNA at the ura3Δ0 locus in the yeast Saccharomyces cerevisiae.

    PubMed

    Fukunaga, Tomoaki; Cha-Aim, Kamonchai; Hirakawa, Yuki; Sakai, Ryota; Kitagawa, Takao; Nakamura, Mikiko; Nonklang, Sanom; Hoshida, Hisashi; Akada, Rinji

    2013-06-01

    Recombinant DNAs are traditionally constructed using Escherichia coli plasmids. In the yeast Saccharomyces cerevisiae, chromosomal gene targeting is a common technique, implying that the yeast homologous recombination system could be applied for recombinant DNA construction. In an attempt to use a S. cerevisiae chromosome for recombinant DNA construction, we selected the single ura3Δ0 locus as a gene targeting site. By selecting this single locus, repeated recombination using the surrounding URA3 sequences can be performed. The recombination system described here has several advantages over the conventional plasmid system, as it provides a method to confirm the selection of correct recombinants because transformation of the same locus replaces the pre-existing selection marker, resulting in the loss of the marker in successful recombinations. In addition, the constructed strains can serve as both PCR templates and hosts for preparing subsequent recombinant strains. Using this method, several yeast strains that contained selection markers, promoters, terminators and target genes at the ura3Δ0 locus were successfully generated. The system described here can potentially be applied for the construction of any recombinant DNA without the requirement for manipulations in E. coli. Interestingly, we unexpectedly found that several G/C-rich sequences used for fusion PCR lowered gene expression when located adjacent to the start codon.

  12. Physical Mapping in a Triplicated Genome: Mapping the Downy Mildew Resistance Locus Pp523 in Brassica oleracea L.

    PubMed Central

    Carlier, Jorge D.; Alabaça, Claudia S.; Sousa, Nelson H.; Coelho, Paula S.; Monteiro, António A.; Paterson, Andrew H.; Leitão, José M.

    2011-01-01

    We describe the construction of a BAC contig and identification of a minimal tiling path that encompass the dominant and monogenically inherited downy mildew resistance locus Pp523 of Brassica oleracea L. The selection of BAC clones for construction of the physical map was carried out by screening gridded BAC libraries with DNA overgo probes derived from both genetically mapped DNA markers flanking the locus of interest and BAC-end sequences that align to Arabidopsis thaliana sequences within the previously identified syntenic region. The selected BAC clones consistently mapped to three different genomic regions of B. oleracea. Although 83 BAC clones were accurately mapped within a ∼4.6 cM region surrounding the downy mildew resistance locus Pp523, a subset of 33 BAC clones mapped to another region on chromosome C8 that was ∼60 cM away from the resistance gene, and a subset of 63 BAC clones mapped to chromosome C5. These results reflect the triplication of the Brassica genomes since their divergence from a common ancestor shared with A. thaliana, and they are consonant with recent analyses of the C genome of Brassica napus. The assembly of a minimal tiling path constituted by 13 (BoT01) BAC clones that span the Pp523 locus sets the stage for map-based cloning of this resistance gene. PMID:22384370

  13. Genome-Wide Association Study Identifies a Novel Canine Glaucoma Locus

    PubMed Central

    Ahonen, Saija J.; Pietilä, Elina; Mellersh, Cathryn S.; Tiira, Katriina; Hansen, Liz; Johnson, Gary S.; Lohi, Hannes

    2013-01-01

    Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG), primary open-angle (POAG) and primary congenital glaucoma (PCG). Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT) in which it is a late-onset (>7 years) disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively) in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63×10−10, OR = 32 for homozygosity). Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease. PMID:23951034

  14. Age and sex based genetic locus heterogeneity in type 1 diabetes

    PubMed Central

    Paterson, A.; Petronis, A.

    2000-01-01

    BACKGROUND—Two genome scans for susceptibility loci for type 1 diabetes using large collections of families have recently been reported. Apart from strong linkage in both studies of the HLA region on chromosome 6p, clear consistent evidence for linkage was not observed at any other loci. One possible explanation for this is a high degree of locus heterogeneity in type 1 diabetes, and we hypothesised that the sex of affected offspring, age of diagnosis, and parental origin of shared alleles may be the bases of heterogeneity at some loci.
METHODS—Using data from a genome wide linkage study of 356 affected sib pairs with type 1 diabetes, we performed linkage analyses using parental origin of shared alleles in subgroups based on (1) sex of affected sibs and (2) age of diagnosis.
RESULTS—Among the results obtained, we observed that evidence for linkage to IDDM4 on chromosome 11q13 occurred predominantly from opposite sex, rather than same sex sib pairs. At a locus on chromosome 4q, evidence for linkage was observed in sibs where one was diagnosed above the age of 10 years and the other diagnosed below 10 years of age.
CONCLUSIONS—We show that heterogeneity tests based on age of diagnosis, sex of affected subject, and parental origin of shared alleles may be helpful in reducing locus heterogeneity in type 1 diabetes. If repeated in other samples, these findings may assist in the mapping of susceptibility loci for type 1 diabetes. Similar analyses can be recommended in other complex diseases.


Keywords: type 1 diabetes; age of diagnosis; sex; parental origin of alleles PMID:10699054

  15. Machado-Joseph disease in pedigrees of Azorean descent is linked to chromosome 14

    SciTech Connect

    George-Hyslop, P. St.; McLachlan, D.R.C.; Lang, A.E.; Wherrett, J.R.; Rogaeva, E.; Tsuda, T.; Rogaev, E.I.; Liang, Y.; Huterer, J.; Kennedy, J. )

    1994-07-01

    A locus for Machado-Joseph disease (MJD) has recently been mapped to a 30-cM region of chromosome 14q in five pedigrees of Japanese descent. MJD is a clinically pleomorphic neurodegenerative disease that was originally described in subjects of Azorean descent. In light of the nonallelic heterogeneity in other inherited spinocerebellar ataxias, the authors were interested to determine if the MJD phenotype in Japanese and Azorean pedigrees arose from mutations at the same locus. They provide evidence that MJD in five pedigrees of Azorean descent is also linked to chromosome 14q in an 18-cM region between the markers D14S67 and AACT (multipoint lod score +7.00 near D14S81). They also report molecular evidence for homozygosity at the MJD locus in an MJD-affected subject with severe, early-onset symptoms. These observations confirm the initial report of linkage of MJD to chromosome 14; suggest that MJD in Japanese and Azorean subjects may represent allelic or identical mutations at the same locus; and provide one possible explanation (MJD gene dosage) for the observed phenotypic heterogeneity in this disease. 22 refs., 3 figs., 1 tab.

  16. Transvection at the end of the truncated chromosome in Drosophila melanogaster.

    PubMed Central

    Savitsky, Mikhail; Kahn, Tatyana; Pomerantseva, Ekaterina; Georgiev, Pavel

    2003-01-01

    The phenomenon of transvection is well known for the Drosophila yellow locus. Thus enhancers of a promoterless yellow locus in one homologous chromosome can activate the yellow promoter in the other chromosome where the enhancers are inactive or deleted. In this report, we examined the requirements for trans-activation of the yellow promoter at the end of the deficient chromosome. A number of truncated chromosomes ending in different areas of the yellow regulatory region were examined in combination with the promoterless y alleles. We found that trans-activation of the yellow promoter at the end of a deficient chromosome required approximately 6 kb of an additional upstream sequence. The nature of upstream sequences affected the strength of transvection: addition of gypsy sequences induced stronger trans-activation than addition of HeT-A or yellow sequences. Only the promoter proximal region (within -158 bp of the yellow transcription start) was essential for trans-activation; i.e., transvection did not require extensive homology in the yellow upstream region. Finally, the yellow enhancers located on the two pairing chromosomes could cooperatively activate one yellow promoter. PMID:12702682

  17. The gene for cherubism maps to chromosome 4p16.

    PubMed Central

    Tiziani, V; Reichenberger, E; Buzzo, C L; Niazi, S; Fukai, N; Stiller, M; Peters, H; Salzano, F M; Raposo do Amaral, C M; Olsen, B R

    1999-01-01

    Cherubism is an autosomal dominant disorder that may be related to tooth development and eruption. It is a disorder of age-related bone remodeling, mostly limited to the maxilla and the mandible, with loss of bone in the jaws and its replacement with large amounts of fibrous tissue. We have used a genomewide search with a three-generation family and have established linkage to chromosome 4p16. Three other families affected with cherubism were also genotyped and were mapped to the same locus. The combined LOD score is 4.21 at a recombination fraction of 0, and the locus spans an interval of approximately 22 cM. PMID:10364528

  18. Confirmation of the 2p locus for the mild autosomal recessive lim-girdle muscular dystrophy gene (LGMD2B) in three families allows refinement of the candidate region

    SciTech Connect

    Bashir, R.; Iughetti, P.; Strachan, T.

    1995-05-01

    The mild autosomal recessive limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of muscle diseases. The first gene to be mapped and associated with this phenotype was a locus on 15q geographic isolate. These results have been confirmed in other populations, but it was shown that there is genetic heterogeneity for this form of LGMD. Recently, a second locus has been mapped to chromosome 2p. The confirmation of the mapping of this second locus in LGMD families from different populations is of utmost importance for the positional cloning of this gene (HGMW-approved symbol LGMD2B). In this publication, haplotypes generated from five chromosome 2 markers from all of the known large families linked to chromosome 2p are reported together with the recombinants that show the current most likely location of the LGMD 2B gene. 9 refs., 2 figs., 1 tab.

  19. Somatic cell genotoxicity at the glycophorin A locus in humans

    SciTech Connect

    Jensen, R.H.; Grant, S.G.; Langlois, R.G.; Bigbee, W.L.

    1990-12-28

    We have developed an assay for detecting variant erythrocytes that occur as a result of in vivo allele loss at the glycophorin A (GPA) locus on chromosome 4 in humans. This gene codes for an erythroid- specific cell surface glycoprotein, and with our assay we are able to detect rare variant erythrocytes that have lost expression of one of the two GPA alleles. Two distinctly different variant cell types are detected with this assay. One variant cell type (called N{O}) is hemizygous. Our assay also detects homozygous variant erythrocytes that have lost expression of the GPA(M) allele and express the GPA(N) allele at twice the heterozygous level. The results of this assay are an enumeration of the frequency of N{O} and NN variant cell types for each individual analyzed. These variant cell frequencies provide a measure of the amount of somatic cell genotoxicity that has occurred at the GPA locus. Such genotoxicity could be the result of (1) reactions of toxic chemicals to which the individual has been exposed, or (2) high energy radiation effects on erythroid precursor cells, or (3) errors in DNA replication or repair in these cells of the bone marrow. Thus, the GPA-based variant cell frequency can serve as a biodosimeter that indicates the amount of genotoxic exposure each individual has received. Because two very different kinds of variant cells are enumerated, different kinds of genotoxicity should be distinguishable. Results of the GPA somatic genotoxicity assay may also provide valuable information for cancer-risk estimation on each individual. 16 refs.

  20. Genetic and physical mapping of the bovine X chromosome.

    PubMed

    Yeh, C C; Taylor, J F; Gallagher, D S; Sanders, J O; Turner, J W; Davis, S K

    1996-03-01

    Three hundred eighty reciprocal backcross and F(2) full sib progeny from 33 families produced by embryo transfer from 77 Angus (Bos taurus), Brahman (Bos indicus), and F1 parents and grandparents were used to construct genetic maps of the bovine X and Y chromosomes. Ml individuals were scored for 15 microsatellite loci, with an average of 608 informative meioses per locus. The length of the bovine X chromosome genetic map was 118.7 cM (female only) and of the pseudoautosomal region was 13.0 cM (male only). The 15-marker framework map in Kosambi centimorgans is [BM6017-6.1 -TGLA89-35.8-TEXAN13-3.4-TGLA128-1.3 -BM2713 -21.1 -BM4604-2.4-BR215 - 12.9-TGLA68-10.0-BM4321 - 1.0-HEL14-4.9-TGLA15-2.3-INRA12O- 12.5-TGLA325- 1.6-MAF45-3.2-INRA3O], with an average interval of 7.91 cM. Clones containing pseudoautosomal or sex-linked microsatellites were isolated from a bovine bacterial artificial chromosome library and were physically mapped to bovine metaphase chromosomes by fluorescence in situ hybridization to orient the X and Y chromosome maps. BAC57, containing the pseudoautosomal microsatellite INRA3O, mapped to the distal end of the long arm of the X chromosome at q42-ter and to the short arm of the Y chromosome at p13-ter. This confirms the published assignment of this region to Ypl2-ter, but challenges the published assignment of Xpl4-ter and thus reorients the X chromosome physical map. BAC2O4, containing the X-linked microsatellite BM4604, mapped to the middle of the long arm of the X chromosome at q26-q31. The position of the physically mapped markers indicates either a lack of microsatellite markers for a large (30 to 50 cM) region of the short arm of the X chromosome or heterogeneity of recombination along the X chromosome. PMID:8833151

  1. The epigenetic stability of the locus control region-deficient IgH locus in mouse hybridoma cells is a clonally varying, heritable feature.

    PubMed Central

    Ronai, Diana; Berru, Maribel; Shulman, Marc J

    2004-01-01

    Cis-acting elements such as enhancers and locus control regions (LCRs) prevent silencing of gene expression. We have shown previously that targeted deletion of an LCR in the immunoglobulin heavy-chain (IgH) locus creates conditions in which the immunoglobulin micro heavy chain gene can exist in either of two epigenetically inherited states, one in which micro expression is positive and one in which micro expression is negative, and that the positive and negative states are maintained by a cis-acting mechanism. As described here, the stability of these states, i.e., the propensity of a cell to switch from one state to the other, varied among subclones and was an inherited, clonal feature. A similar variation in stability was seen for IgH loci that both lacked and retained the matrix attachment regions associated with the LCR. Our analysis of cell hybrids formed by fusing cells in which the micro expression had different stabilities indicated that stability was also determined by a cis-acting feature of the IgH locus. Our results thus show that a single-copy gene in the same chromosomal location and in the presence of the same transcription factors can exist in many different states of expression. PMID:15166165

  2. Genetic and Genomic Dissection of the Cochliobolus heterostrophus Tox1 Locus Controlling Biosynthesis of the Polyketide Virulence Factor T-toxin

    SciTech Connect

    Turgeon, Barbara G.; Baker, Scott E.

    2007-04-27

    Fungal pathogenesis to plants is an intricate developmental process requiring biological components found in most fungi, as well as factors that are unique to fungal taxa that participate in particular fungus–plant interactions. The host-selective polyketide toxin known as T-toxin produced by Cochliobolus heterostrophus race T, a highly virulent pathogen of maize, is an intriguing example of the latter type of virulence determinant. The Tox1 locus, which controls biosynthesis of T-toxin, originally defined as a single genetic locus, it is, in fact, two exceedingly complex loci on two chromosomes that are reciprocally translocated with respect to their counterparts in weakly pathogenic race O. Race O lacks the Tox1 locus and does not produce T-toxin. Highly virulent race T was first recognized when it caused an epidemic of Southern Corn Leaf Blight, which devastated the US corn crop in 1970. The evolutionary origin of the Tox1 locus remains unknown.

  3. Linkage analysis suggests a locus of ichthyosis vulgaris on 1q22.

    PubMed

    Zhong, Wei; Cui, Bin; Zhang, Yizhi; Jiang, Haisong; Wei, Shengcai; Bu, Lei; Zhao, Guoping; Hu, Landian; Kong, Xiangyin

    2003-01-01

    Ichthyosis vulgaris (IV) is an inherited scaling skin disorder with a prevalence estimated at 2.29% in China. The gene responsible for this disorder has not been elucidated. To find the disease gene, we ascertained two Chinese IV families. Linkage analysis identified an IV locus on chromosome 1q22 with a maximum two-point Lod score of 2.47 at D1S1653 (theta=0.00). Haplotype analysis placed the critical region in a 7-cM interval defined by D1S1653 and D1S2675. These results provide the basis for further identifying the gene responsible for IV disorder.

  4. The Finnish lapphund retinal atrophy locus maps to the centromeric region of CFA9

    PubMed Central

    Aguirre-Hernández, Jesús; Wickström, Kaisa; Sargan, David R

    2007-01-01

    Background Dogs have the second largest number of genetic diseases, after humans. Among the diseases present in dogs, progressive retinal atrophy has been reported in more than a hundred breeds. In some of them, the mutation has been identified and genetic tests have allowed the identification of carriers, thus enabling a drastic reduction in the incidence of the disease. The Finnish lapphund is a dog breed presenting late-onset progressive retinal atrophy for which the disease locus remains unknown. Results In this study we mapped the progressive retinal atrophy locus in the Finnish lapphund using a DNA pooling approach, assuming that all affected dogs within the breed share the same identical-by descent-mutation as the cause of the disease (genetic homogeneity). Autosomal recessive inheritance was also assumed, after ruling out, from pedigree analysis, dominant and X-linked inheritance. DNA from 12 Finnish lapphund cases was mixed in one pool, and DNA from 12 first-degree relatives of these cases was mixed to serve as the control pool. The 2 pools were tested with 133 microsatellite markers, 3 of which showed a shift towards homozygosity in the cases. Individual genotyping with these 3 markers confirmed homozygosity for the GALK1 microsatellite only (chromosome 9). Further individual genotyping with additional samples (4 cases and 59 controls) confirmed the association between this marker and the disease locus (p < 0.001). Closely related to this breed are the Swedish lapphund and the Lapponian herder for which a small number of retinal atrophy cases have been reported. Swedish lapphund cases, but not Lapponian herder cases, had the same GALK1 microsatellite genotype as Finnish lapphund cases. Conclusion The locus for progressive rod-cone degeneration is known to be close to the GALK1 locus, on the telomeric region of chromosome 9, where the retinal atrophy locus of the Finnish lapphund has been mapped. This suggests that the disease in this breed, as well as in

  5. Linkage analyses of chromosome 6 loci, including HLA, in familial aggregations of Crohn disease

    SciTech Connect

    Hugot, J.P.; Laurent-Puig, P.; Gower-Rousseau, C.; Caillat-Zueman, S.; Beaugerie, L.; Dupas, J.L.; Van Gossum, A.; Bonaiti-Pellie, C.; Cortot, A.

    1994-08-15

    Segregation analyses of familial aggregations of Crohn disease have provided consistent results pointing to the involvement of a predisposing gene with a recessive mode of inheritance. Although extensively investigated, the role played by human leucocyte antigen (HLA) genes in this inflammatory bowel disease remains elusive and the major histocompatibility complex is a candidate region for the mapping of the Crohn disease susceptibility gene. A total of 25 families with multiple cases of Crohn disease was genotyped for HLA DRB1 and for 16 highly polymorphic loci evenly distributed on chromosome 6. The data were subjected to linkage analysis using the lod score method. Neither individual nor combined lod scores for any family and for any locus tested reached values suggesting linkage or genetic heterogeneity. The Crohn disease predisposing locus was excluded from the whole chromosome 6 with lod scores less than -2. It was excluded from the major histocompatibility complex and from 91% of the chromosome 6 genetic map with lod scores less than -4. The major recessive gene involved in genetic predisposition to Crohn disease does not reside on the major histocompatibility complex nor on any locus mapping to chromosome 6. 37 refs., 2 figs., 2 tabs.

  6. Evidence for locus heterogeneity in autosomal dominant limb-girdle muscular dystrophy

    SciTech Connect

    Speer, M.C.; Stajich, J.M.; Gaskell, P.C.

    1995-12-01

    Limb-girdle muscular dystrophy (LGMD) is a diagnostic classification encompassing a broad group of proximal myopathies. A gene for the dominant form of LGMD (LGMD1A) has recently been localized to a 7-cM region of chromosome 5q between D5S178 and IL9. We studied three additional dominant LGMD families for linkage to these two markers and excluded all from localization to this region, providing evidence for locus heterogeneity within the dominant form of LGMD. Although the patterns of muscle weakness were similar in all families studied, the majority of affected family members in the chromosome 5-linked pedigree have a dysarthric speech pattern, which is not present in any of the five unlinked families. The demonstration of heterogeneity within autosomal dominant LGMD is the first step in attempting to subclassify these families with similar clinical phenotypes on a molecular level. 33 refs., 1 fig., 2 tabs.

  7. Prezygotic isolation, mating preferences, and the evolution of chromosomal inversions.

    PubMed

    Dagilis, Andrius J; Kirkpatrick, Mark

    2016-07-01

    Chromosomal inversions are frequently implicated in isolating species. Models have shown how inversions can evolve in the context of postmating isolation. Inversions are also frequently associated with mating preferences, a topic that has not been studied theoretically. Here, we show how inversions can spread by capturing a mating preference locus and one or more loci involved with epistatic incompatibilities. Inversions can be established under broad conditions ranging from near panmixis to nearly complete speciation. These results provide a hypothesis to explain the growing number of examples of inversions associated with premating isolating mechanisms. PMID:27174252

  8. Distribution of the mammalian Stat gene family in mouse chromosomes

    SciTech Connect

    Copeland, N.G.; Gilbert, D.J.; Jenkins, N.A.

    1995-09-01

    Studies of transcriptional activation by interferons and a variety of cytokines have led to the identification of a family of proteins that serve as signal transducers and activators of transcription, Stats. Here, we report that the seven mouse Stat loci map in three clusters, with each cluster located on a different mouse autosome. The data suggest that the family has arisen via a tandem duplication of the ancestral locus, followed by dispersion of the linked loci to different mouse chromosomes. 28 refs., 1 fig., 1 tab.

  9. Evidence for meiotic drive at the myotonic dystrophy locus

    SciTech Connect

    Shaw, A.M.; Barnetson, R.A.; Phillips, M.F.

    1994-09-01

    Myotonic dystrophy (DM), an autosomal dominant disorder, is the most common form of adult muscular dystrophy, affecting at least 1 in 8000 of the population. It is a multisystemic disorder, primarily characterized by myotonia, muscle wasting and cataract. The molecular basis of DM is an expanded CTG repeat located within the 3{prime} untranslated region of a putative serine-threonine protein kinase on chromosome 19q13.3. DM exhibits anticipation, that is, with successive generations there is increasing disease severity and earlier age of onset. This mechanism and the fact that the origin of the disease has been attributed to one or a small number of founder chromosomes suggests that, in time, DM should die out. Meiotic drive has been described as a way in which certain alleles are transmitted to succeeding generations in preference to others: preferential transmission of large CTG alleles may account for their continued existence in the gene pool. There is evidence that a CTG allele with > 19 repeats may gradually increase in repeat number over many generations until it is sufficiently large to give a DM phenotype. We report a study of 495 transmissions from individuals heterozygous for the CTG repeat and with repeat numbers within the normal range (5-30). Alleles were simply classified as large or small relative to the other allele in an individual. Of 242 male meioses, 126 transmissions from parent to child were of the larger allele to their offspring (57.7%, p=0.014). This shows that there is strong evidence for meiotic drive favoring the transmission of the larger DM allele in unaffected individuals. Contrary to a previous report of meiotic drive in the male, we have shown that females preferentially transmit the larger DM allele. Taken together, the data suggest the occurrence of meiotic drive in both males and females in this locus.

  10. Evolution of sex-specific wing shape at the widerwing locus in four species of Nasonia.

    PubMed

    Loehlin, D W; Enders, L S; Werren, J H

    2010-03-01

    How do morphological differences between species evolve at the genetic level? This study investigates the genetic basis of recent divergence in male wing size between species of the model parasitoid wasp Nasonia. The forewings of flightless Nasonia vitripennis males are 2.3 times smaller than males of their flighted sister species N. giraulti. We describe a major genetic contributor to this difference: the sex-specific widerwing (wdw) locus, which we have backcrossed from N. giraulti into N. vitripennis and mapped to an 0.9 megabase region of chromosome 1. This introgression of wdw from large-winged N. giraulti into small-winged N. vitripennis increases male but not female forewing width by 30% through wing region-specific size changes. Indirect evidence suggests that cell number changes across the wing explain the majority of the wdw wing-size difference, whereas changes in cell size are important in the center of the wing. Introgressing the same locus from the other species in the genus, N. longicornis and N. oneida, into N. vitripennis produces intermediate and large male wing sizes. To our knowledge, this is the first study to introgress a morphological quantitative trait locus (QTL) from multiple species into a common genetic background. Epistatic interactions between wdw and other QTL are also identified by introgressing wdw from N. vitripennis into N. giraulti. The main findings are (1) the changes at wdw have sex- and region-specific effects and could, therefore, be regulatory, (2) the wdw locus seems to be a co-regulator of cell size and cell number, and (3) the wdw locus has evolved different wing width effects in three species.

  11. Molecular characterization of the tia invasion locus from enterotoxigenic Escherichia coli.

    PubMed Central

    Fleckenstein, J M; Kopecko, D J; Warren, R L; Elsinghorst, E A

    1996-01-01

    Enterotoxigenic Escherichia coli (ETEC) shares with other diarrheal pathogens the capacity to invade epithelial cell lines originating from the human ileum or colon, although the role of invasion in ETEC pathogenesis remains undefined. Two distinct loci (tia and tib) that direct noninvasive E. coli to adhere to and invade intestinal epithelial cell lines have previously been isolated from cosmid libraries of the classical ETEC strain H10407. Here, we report the molecular characterization of the tia locus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of cellular fractions of E. coli DH5alpha carrying the tia-positive cosmids and recombinant plasmid subclones revealed that this locus directs the production of a 25-kDa protein (the Tia protein) that is localized to the outer membrane. The tia locus was subcloned to a maximum of 2 kb and mutagenized with bacteriophage Mud. Synthesis of this protein was directly correlated with the ability of subclones and Mud transposon mutants to adhere to and invade epithelial cells. Sequencing of the tia locus identified a 756-bp open reading frame. All transposon insertions resulting in an invasion-negative phenotype mapped to this open reading frame. The open reading frame was amplified and directionally cloned behind the lac promoter of pHG165. This construct directed DHalpha to express a 25-kDa protein and to adhere to and invade epithelial cells. The role of the tia gene in directing epithelial adherence and invasion was further assessed by the construction of chromosomal tia deletion derivatives of the parent ETEC strain, H10407. These tia deletion strains were noninvasive and lacked the ability to adhere to human ileocecal cells. The tia gene shares limited homology with the Yersinia ail locus and significant homology with the hra1 agglutinin gene cloned from a porcine ETEC strain. Additionally, tia probes hybridized to geographically diverse ETEC strains, as well as some enteropathogenic E. coli

  12. Evolution of sex-specific wing shape at the widerwing locus in four species of Nasonia

    PubMed Central

    Loehlin, David W.; Enders, Laramy S.; Werren, John H.

    2009-01-01

    How do morphological differences between species evolve at the genetic level? This study investigates the genetic basis of recent divergence in male wing size between species of the model parasitoid wasp Nasonia. The forewings of flightless N. vitripennis males are 2.3 times smaller than males of their flighted sister species N. giraulti. We describe a major genetic contributor to this difference: the sex-specific widerwing (wdw) locus, which we have backcrossed from N. giraulti into N. vitripennis and mapped to an 0.9 megabase region of chromosome 1. This introgression of wdw from large-winged N. giraulti into small-winged N. vitripennis increases male but not female forewing width by 30% through wing region-specific size changes. Indirect evidence suggests that cell number changes across the wing explain the majority of the wdw wing size difference while changes in cell size are important in the center of the wing. Introgressing the same locus from the other species in the genus, N. longicornis and N. oneida, into N. vitripennis produces intermediate and large male wing sizes. To our knowledge, this is the first study to introgress a morphological quantitative trait locus (QTL) from multiple species into a common genetic background. Epistatic interactions between wdw and other QTL are also identified by introgressing wdw from N. vitripennis into N. giraulti. The main findings are 1) the changes at wdw have sex- and region-specific effects and could therefore be regulatory, 2) the wdw locus appears to be a co-regulator of cell size and cell number, and 3) the wdw locus has evolved different wing width effects in three species. PMID:20087390

  13. Interaction of the Stubble-Stubbloid Locus and the Broad-Complex of Drosophila Melanogaster

    PubMed Central

    Beaton, A. H.; Kiss, I.; Fristrom, D.; Fristrom, J. W.

    1988-01-01

    The 2B5 region on the X chromosome of Drosophila melanogaster forms an early ecdysone puff at the end of the third instar. The region is coextensive with a complex genetic locus, the Broad-Complex (BR-C). The BR-C is a regulatory gene that contains two major functional domains, the br domain and the l(1)2Bc domain. BR-C mutants prevent metamorphosis, including morphogenesis of imaginal discs; br mutants prevent elongation and eversion of appendages and l(1)2Bc mutants prevent fusion of the discs. The Stubble-stubbloid (Sb-sbd) locus at 89B9-10 is best known for the effects of its mutants on bristle structure. Mutants of the BR-C and the Sb-sbd locus interact to produce severe malformation of appendages. Viable heteroallelic and homoallelic combinations of Sb-sbd mutants, including loss-of-function mutants, affect the elongation of imaginal disc appendages. Thus, the Sb-sbd(+) product is essential for normal appendage elongation. Sb-sbd mutants, however, do not affect eversion or fusion of discs. Correspondingly, only BR-C mutants deficient in br function interact with Sb-sbd mutants. The interaction occurs in deficiency heterozygotes using single, wild-type doses of the BR-C, of the Sb-sbd locus, or of both loci. These last results are formally consistent with the possibility that the BR-C acts as a positive regulator of the Sb-sbd locus. The data do not exclude other possible nonregulatory interactions between the two loci, e.g., interactions between the products of both genes. PMID:3143619

  14. Genetic linkage of autosomal dominant primary open angle glaucoma to chromosome 3q in a Greek pedigree.

    PubMed

    Kitsos, G; Eiberg, H; Economou-Petersen, E; Wirtz, M K; Kramer, P L; Aspiotis, M; Tommerup, N; Petersen, M B; Psilas, K

    2001-06-01

    A locus for juvenile onset open angle glaucoma (OAG) has been assigned to chromosome 1q in families with autosomal dominant inheritance (GLC1A), due to mutations in the TIGR/MYOC gene. For adult onset OAG, called primary open angle glaucoma or POAG, five loci have so far been mapped to different chromosomes (GLC1B-GLC1F). Except for the GLC1B locus, the other POAG loci have so far been reported only in single large pedigrees. We studied a large family identified in Epirus, Greece, segregating POAG in an autosomal dominant fashion. Clinical findings included increased cup to disc ratio (mean 0.7), characteristic glaucomatous changes in the visual field, and intraocular pressure before treatment more than 21 mmHg (mean 31 mmHg), with age at diagnosis 33 years and older. Linkage analysis was performed between the disease phenotype and microsatellite DNA polymorphisms. Linkage was established with a group of DNA markers located on chromosome 3q, where the GLC1C locus has previously been described in one large Oregon pedigree. A maximal multipoint lod score of 3.88 was obtained at marker D3S1763 (penetrance 80%). This represents the second POAG family linked to the GLC1C locus on chromosome 3q, and haplotype analysis in the two families suggests an independent origin of the genetic defect.

  15. A major locus expressed in the male gametophyte with incomplete penetrance is responsible for in situ gynogenesis in maize.

    PubMed

    Barret, P; Brinkmann, M; Beckert, M

    2008-08-01

    In flowering plants, double fertilization occurs when the egg cell and the central cell are each fertilized by one sperm cell. In maize, some lines produce pollen capable of inducing in situ gynogenesis thereby leading to maternal haploids that originate exclusively from the female plant. In this paper, we present a genetic analysis of in situ gynogenesis in maize. Using a cross between non-inducing and inducing lines, we identified a major locus on maize chromosome 1 controlling in situ gynogenesis (ggi1, for gynogenesis inducer 1). Fine mapping of this locus was performed, and BAC physical contigs spanning the locus were identified using the rice genome as anchor. Genetic component analysis showed that (a) a segregation distortion against the inducer parent was present at this locus, (b) segregation resulted only from male deficiency and (c) there was a correlation between the rate of segregation distortion and the level of gynogenetic induction. In addition, our results showed that the genotype of the pollen determined its capacity to induce the formation of a haploid female embryo, indicating gametophytic expression of the character with incomplete penetrance. We propose the occurrence of a gametophytic-specific process which leads to segregation distortion at the ggi1 locus as