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Sample records for 4q25 chromosomal locus

  1. Mapping of a Gene for Long QT Syndrome to Chromosome 4q25-27

    PubMed Central

    Schott, Jean-Jacques; Charpentier, Flavien; Peltier, Sophie; Foley, Patrick; Drouin, Emmanuel; Bouhour, Jean-Brieuc; Donnelly, Patricia; Vergnaud, Gilles; Bachner, Lucien; Moisan, Jean-Paul; Le Marec, Hervé; Pascal, Olivier

    1995-01-01

    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. PMID:7485162

  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. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation

    PubMed Central

    Kääb, Stefan; Darbar, Dawood; van Noord, Charlotte; Dupuis, Josée; Pfeufer, Arne; Newton-Cheh, Christopher; Schnabel, Renate; Makino, Seiko; Sinner, Moritz F.; Kannankeril, Prince J.; Beckmann, Britt M.; Choudry, Subbarao; Donahue, Brian S.; Heeringa, Jan; Perz, Siegfried; Lunetta, Kathryn L.; Larson, Martin G.; Levy, Daniel; MacRae, Calum A.; Ruskin, Jeremy N.; Wacker, Annette; Schömig, Albert; Wichmann, H.-Erich; Steinbeck, Gerhard; Meitinger, Thomas; Uitterlinden, André G.; Witteman, Jacqueline C.M.; Roden, Dan M.; Benjamin, Emelia J.; Ellinor, Patrick T.

    2009-01-01

    Aims A recent genome-wide association study identified a haplotype block on chromosome 4q25 associated with atrial fibrillation (AF). We sought to replicate this association in four independent cohorts. Methods and results The Framingham Heart Study and Rotterdam Study are community-based longitudinal studies. The Vanderbilt AF Registry and German AF Network (AFNet) are case–control studies. Participants with AF (n = 3508) were more likely to be male and were older than referent participants (n = 12 173; Framingham 82 ± 10 vs. 71 ± 13 years; Rotterdam 73 ± 8 vs. 69 ± 9 years; Vanderbilt 54 ± 14 vs. 57 ± 14 years; AFNet 62 ± 12 vs. 49 ± 14 years). Single nucleotide polymorphism (SNP) rs2200733 was associated with AF in all four cohorts, with odds ratios (ORs) ranging from 1.37 in Rotterdam [95% confidence interval (CI) 1.18–1.59; P = 3.1 × 10−5] to 2.52 in AFNet (95% CI 2.22–2.8; P = 1.8 × 10−49). There also was a significant association between AF and rs10033464 in Framingham (OR 1.34; 95% CI 1.03–1.75; P = 0.031) and AFNet (OR 1.30; 95% CI 1.13–1.51; P = 0.0002), but not Vanderbilt (OR 1.16; 95% CI 0.86–1.56; P = 0.33). A meta-analysis of the current and prior AF studies revealed an OR of 1.90 (95% CI 1.60–2.26; P = 3.3 × 10−13) for rs2200733 and of 1.36 (95% CI 1.26–1.47; P = 6.7 × 10−15) for rs10033464. Conclusion The non-coding SNPs rs2200733 and rs10033464 are strongly associated with AF in four cohorts of European descent. These results confirm the significant relations between AF and intergenic variants on chromosome 4. PMID:19141561

  4. Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25 microdeletion.

    PubMed

    Verhoeven, Willem M A; Egger, Jos I M; Goffin, Luc; van Zutven, Laura J C M; Mancini, Grazia M S

    2013-06-01

    A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination disclosed obsessive, ritualistic behaviours and vague ideas of reference. Neuropsychological assessment demonstrated mild intellectual disability, mental inflexibility and incongruent affect. MRI-scanning of the brain showed no relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be causative for the developmental delay, perseverative cognitive phenotype and dysmorphisms. To the authors knowledge, this is the first report of a de novo 4q25 microdeletion that presents with a specific behavioural phenotype. PMID:23542664

  5. Atrial Fibrillation Associated Chromosome 4q25 Variants Are Not Associated with PITX2c Expression in Human Adult Left Atrial Appendages

    PubMed Central

    Gore-Panter, Shamone R.; Hsu, Jeffery; Hanna, Peter; Gillinov, A. Marc; Pettersson, Gosta; Newton, David W.; Moravec, Christine S.; Van Wagoner, David R.; Chung, Mina K.; Barnard, John; Smith, Jonathan D.

    2014-01-01

    Atrial Fibrillation (AF), the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS) have identified that the single nucleotide polymorphisms (SNPs) most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, ∼54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic. PMID:24465984

  6. Polymorphism rs2200733 at chromosome 4q25 is associated with atrial fibrillation recurrence after radiofrequency catheter ablation in the Chinese Han population

    PubMed Central

    Chen, Feifei; Yang, Yanzong; Zhang, Rongfeng; Zhang, Shulong; Dong, Yingxue; Yin, Xiaomeng; Chang, Dong; Yang, Zhiqiang; Wang, Kejing; Gao, Lianjun; Xia, Yunlong

    2016-01-01

    To test polymorphisms rs2200733 (chromosome 4q25) and rs2106261 (ZFHX3) were associated with AF recurrence after catheter ablation in a Chinese Han cohort. A total of 235 AF patients who underwent catheter ablation were recruited consecutively. Two polymorphisms were amplified by polymerase chain reaction and genotyped using high resolution melting analysis. Primary endpoints for AF recurrence were defined as the time to the first recurrence of atrial tachycardia/flutter/fibrillation (AT/AF). AT/AF recurrence was observed in 76 patients (35%). Allelic analysis demonstrated that rs2200733 was strongly associated with AF recurrence after ablation (P = 0.011) and the minor allele T increased the risk for recurrence (OR = 1.715). Diameters of the right atrium as well as the left and right superior pulmonary veins (PVs) were associated with rs2200733 in different genetic models (P = 0.040, 0.047 and 0.028, respectively). No significant association was detected between rs2106261 and AT/AF recurrence after ablation or atrial/PV diameters in any models. On multivariate Cox regression analysis, only rs2200733 was an independent factor of AF recurrence after ablation (HR = 0.532, P = 0.022). In Chinese Han population, rs2200733 but not rs2106261 is associated with AT/AF recurrence after ablation. The patients with genotype TT have larger size of right atrium and superior PVs than those of CC genotype. The findings suggest that rs2200733 may play a key role in regulating proper development and differentiation of atria/PVs. PMID:27158361

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Axenfeld-Rieger syndrome: further clinical and array delineation of four unrelated patients with a 4q25 microdeletion.

    PubMed

    Titheradge, Hannah; Togneri, Fiona; McMullan, Dominic; Brueton, Louise; Lim, Derek; Williams, Denise

    2014-07-01

    Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder with variable expressivity. It is characterized by dysgenesis of the anterior segment of the eye together with dental, cardiac, and umbilical anomalies. There is a high incidence of secondary high tension glaucoma. It is a genetically heterogeneous condition due to deletion or mutations of FOXC1 (6p25) or PITX2 (4q25). We report on four unrelated patients with overlapping microdeletions encompassing PITX2 at 4q25. We compare the genotypes and phenotypes of these newly described ARS patients and discuss the involvement of contiguous genes. Patients 1, 2, and 3 had mild learning difficulties, not typically seen in patients with ARS. We implicate the adjacent neuronally expressed genes; NEUROG2, UGT8, NDST3, and PRSS12 as potentially causal. Our findings support the use of microarray analysis in ARS patients for full prognostic information in infants presenting with ARS-like phenotypes. PMID:24715413

  13. 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.

  14. 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.

  15. 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.

  16. A familial hypertrophic cardiomyopathy locus maps to chromosome 15q2.

    PubMed Central

    Thierfelder, L; MacRae, C; Watkins, H; Tomfohrde, J; Williams, M; McKenna, W; Bohm, K; Noeske, G; Schlepper, M; Bowcock, A

    1993-01-01

    We report that a gene responsible for familial hypertrophic cardiomyopathy (FHC) in a kindred with a mild degree of cardiac hypertrophy maps to chromosome 15q2. The gene encoding cardiac actin, located on chromosome 15q, was analyzed and excluded as a candidate for FHC at this locus. Two additional families with typical FHC were studied and the disorder in one also maps to the chromosome 15q2 locus. The maximum combined multipoint logarithm of odds score in the two linked families is 6.02. Although these two kindreds reside in the same country, we believe that their disorder is caused by independent mutations in the 15q2 locus because of the clinical and genotypic differences between affected individuals. Mutations in at least four loci can cause FHC: chromosomes 14q1 (beta cardiac myosin heavy chain gene), 1q3, and 15q2 and another unidentified locus, suggesting substantial genetic heterogeneity. PMID:8327508

  17. 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

  18. 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.

  19. 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.

  20. Autotriploid origin of Carassius auratus as revealed by chromosomal locus analysis.

    PubMed

    Qin, Qinbo; Wang, Juan; Hu, Min; Huang, Shengnan; Liu, Shaojun

    2016-06-01

    In the Dongting water system, the Carassius auratus (Crucian carp) complex is characterized by the coexistence of diploid forms (2n=100, 2nCC) and polyploid forms. Chromosomal and karyotypic analyses have suggested that the polyploid C. auratus has a triploid (3n=150, 3nCC) and a tetraploid origin (4n=200), respectively. However, there is a lack of direct genetic evidence to support this conclusion. In this paper, analysis of the 5S rDNA chromosomal locus revealed that the 3nCC is of triploid origin. Analysis of the species-specific chromosomal centromere locus revealed that 3nCC individuals possess three sets of C. auratus-derived chromosomes. Our results provide direct cytogenetic evidence suggesting that individuals with 150 chromosomes are of autotriploid origin within the C. auratus complex. It marks an important contribution to the study of polyploidization and the evolution of vertebrates. PMID:27084707

  1. 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.

  2. A Cis-Acting Locus That Promotes Crossing over between X Chromosomes in Caenorhabditis Elegans

    PubMed Central

    Villeneuve, A. M.

    1994-01-01

    This study reports the characterization of a cis-acting locus on the Caenorhabditis elegans X chromosome that is crucial for promoting normal levels of crossing over specifically between the X homologs and for ensuring their proper disjunction at meiosis I. The function of this locus is disrupted by the mutation me8, which maps to the extreme left end of the X chromosome within the region previously implicated by studies of X;A translocations and X duplications to contain a meiotic pairing site. Hermaphrodites homozygous for a deletion of the locus (Df/Df) or heterozygous for a deletion and the me8 mutation (me8/Df) exhibit extremely high levels of X chromosome nondisjunction at the reductional division; this is correlated with a sharp decrease in crossing over between the X homologs as evidenced both by reductions in genetic map distances and by the presence of achiasmate chromosomes in cytological preparations of oocyte nuclei. Duplications of the wild-type region that are unlinked to the X chromosome cannot complement the recombination and disjunction defects in trans, indicating that this region must be present in cis to the X chromosome to ensure normal levels of crossing over and proper homolog disjunction. me8 homozygotes exhibit an altered distribution of crossovers along the X chromosome that suggests a defect in processivity along the X chromosome of an event that initiates at the chromosome end. Models are discussed in which the cis-acting locus deleted by the Dfs functions as a meiotic pairing center that recruits trans-acting factors onto the chromosomes to nucleate assembly of a crossover-competent complex between the X homologs. This pairing center might function in the process of homolog recognition, or in the initiation of homologous synapsis. PMID:8005443

  3. Deletion mapping of a locus on human chromosome 22 involved in the oncogenesis of meningioma

    SciTech Connect

    Dumanski, J.P.; Carlbom, E.; Collins, V.P.; Nordenskjoeld, M.

    1987-12-01

    The genotypes were analyzed at 11 polymorphic DNA loci (restriction fragment length alleles) on chromosome 22 in tumor and normal tissues from 35 unrelated patients with meningiomas. Sixteen tumors retained the constitutional genotype along chromosome 22, while 14 tumors (40%) showed loss of one constitutional allele at all informative loci, consistent with monosomy 22 in the tumor DNA. The remaining 5 tumors (14%) showed loss of heterozygosity in the tumor DNA at one or more chromosome 22 loci and retained heterozygosity at other loci, consistent with variable terminal deletions of one chromosome 22 in the tumor DNA. The results suggest that a meningioma locus is located distal to the myoglobin locus, within 22q12.3-qter. Multiple loci on their chromosomes also were studied, and 12 of the 19 tumors with losses of chromosome 22 alleles showed additional losses of heterozygosity at loci on one to three other chromosomes. All tumors that retained the constitutional genotype on chromosome 22 also retained heterozygosity at all informative loci on other chromosomes analyzed, suggesting that the rearrangement of chromosome 22 is a primary event in the tumorigenesis of meningioma.

  4. 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 ...

  5. 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...

  6. 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

  7. 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.

  8. 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

  9. A locus for bipolar affective disorder on chromosome 4p.

    PubMed

    Blackwood, D H; He, L; Morris, S W; McLean, A; Whitton, C; Thomson, M; Walker, M T; Woodburn, K; Sharp, C M; Wright, A F; Shibasaki, Y; St Clair, D M; Porteous, D J; Muir, W J

    1996-04-01

    The main clinical feature of bipolar affective disorder is a change of mood to depression or elation. Unipolar disorder, also termed major depressive disorder, describes the occurrence of depression alone without episodes of elevated mood. Little is understood about the underlying causes of these common and severe illnesses which have estimated lifetime prevalences in the region of 0.8% for bipolar and 6% for unipolar disorder. Strong support for a genetic aetiology is found in the familial nature of the condition, the increased concordance of monozygotic over dizygotic twins and adoption studies showing increased rates of illness in children of affected parents. However, linkage studies have met with mixed success. An initial report of linkage on the short arm of chromosome 11 (ref. 4) was revised and remains unreplicated. Reports proposing cosegregation of genes found on the X chromosome with bipolar illness have not been supported by others. More recently bipolar disorder has been reported to be linked with markers on chromosomes 18, 21, 16 and a region on the X chromosome different from those previously suggested. We have carried out a linkage study in twelve bipolar families. In a single family a genome search employing 193 markers indicated linkage on chromosome 4p where the marker D4S394 generated a two-point lod score of 4.1 under a dominant model of inheritance. Three point analyses with neighbouring markers gave a maximum lod score of 4.8. Eleven other bipolar families were typed using D4S394 and in all families combined there was evidence of linkage with heterogeneity with a maximum two-point lod score of 4.1 (theta = 0, alpha = 0.35). PMID:8630499

  10. 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.

  11. DFNB79: reincarnation of a nonsyndromic deafness locus on chromosome 9q34.3.

    PubMed

    Khan, Shahid Yar; Riazuddin, Saima; Shahzad, Mohsin; Ahmed, Nazir; Zafar, Ahmad Usman; Rehman, Atteeq Ur; Morell, Robert J; Griffith, Andrew J; Ahmed, Zubair M; Riazuddin, Sheikh; Friedman, Thomas B

    2010-01-01

    Genetic analysis of an inbred Pakistani family PKDF280, segregating prelingual severe to profound sensorineural hearing loss, provided evidence for a DFNB locus on human chromosome 9q34.3. Co-segregation of the deafness trait with marker D9SH159 was determined by a two-point linkage analysis (LOD score 9.43 at theta=0). Two additional large families, PKDF517 and PKDF741, co-segregate recessive deafness with markers linked to the same interval. Haplotype analyses of these three families refined the interval to 3.84 Mb defined by D9S1818 (centromeric) and D9SH6 (telomeric). This interval overlaps with the previously reported DFNB33 locus whose chromosomal map position has been recently revised and assigned to a new position on chromosome 10p11.23-q21.1. The nonsyndromic deafness locus on chromosome 9q segregating in family PKDF280 was designated DFNB79. We are currently screening the 113 candidate DFNB79 genes for mutations and have excluded CACNA1B, EDF1, PTGDS, EHMT1, QSOX2, NOTCH1, MIR126 and MIR602. PMID:19603065

  12. 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.

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

    PubMed Central

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

    1989-01-01

    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. Images PMID:2557612

  14. 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.

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

    PubMed Central

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

    1997-01-01

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

  16. An autosomal locus predisposing to multiple deletions of mtDNA on chromosome 3p

    SciTech Connect

    Kaukonen, J.A.; Suomalainen, A.; Peltonen, L.; Amati, P.; Zeviani, M.

    1996-04-01

    Autosomal dominant progressive external ophthalmoplegia (adPEO) is a disorder characterized by ptosis, progressive weakness of the external eye muscles, and general muscle weakness. The patients have multiple deletions of mtDNA on Southern blots or in PCR analysis of muscle DNA and a mild deficiency of one or more respiratory-chain enzymes carrying mtDNA-encoded subunits. The pattern of inheritance indicates a nuclear gene defect predisposing to secondary mtDNA deletions. Recently, in one Finnish family, we assigned an adPEO locus to chromosome 10q23.3-24.3 but also excluded linkage to this same locus in two Italian adPEO families with a phenotype closely resembling the Finnish one. We applied a random mapping approach to informative non-10q-linked Italian families to assign the second locus for adPEO and found strong evidence for linkage on chromosome 3p14.1-21.2 in three Italian families, with a maximum two-point lod score of 4.62 at a recombination fraction of .0. However, in three additional families, linkage to the same chromosomal region was clearly absent, indicating further genetic complexity of the adPEO trait. 19 refs., 3 figs., 2 tabs.

  17. Chromosome walking on the TCL1 locus involved in T-cell neoplasia

    SciTech Connect

    Virgilio, L.; Narducci, M.G.; Carotenuto, P.; Camerini, B.; Russo, G. ); Isobe, Masaharu; Kurosawa, Nobuyuki ); Rushdi, A.A.; Croce, C.M. )

    1993-10-15

    The TCL1 locus on chromosome 14 band q32.1 is frequently involved in the chromosomal translocations and inversions with the T-cell receptor genes observed in several T-cell tumors, including T-prolymphocytic leukemias, acute and chronic leukemias associated with the immunodeficiency syndrome ataxia-telangiectasia, and adult T-cell leukemia. All breakpoints cloned in this area have been mapped to 14q32.1, an area distant [approximately]10,000 kb from the immunoglobulin heavy-chain gene locus on chromosome 14q band 32.3. Except for two cases of inversion, no physical linkage of the cloned breakpoints has been reported, nor has a gene been identified in this region. Taking advantage of chromosome-walking techniques and of the P1 phage, the authors cloned and characterized 450 kb of the germ-line TCL1 locus, starting from the breakpoints of two independent T-cell leukemias. The authors show that all molecular rearrangements characterized so far map to these clones, indicating not only that this region is the target of chromosomal rearrangements occurring in this area but also that both inversion and translocations occur within a 300-kb region in the T-cell leukemias. In the attempt to identify a candidate oncogene responsible for the malignant transformation, a CpG island centromeric to the inversions and to the translocations has been identified. Two probes near the CpG island have detected sequences conserved among species, as well as two transcripts in the K562 human erythroleukemia cell line. On the basis of these data, a model of activation of the putative TCL1 oncogene is suggested. 30 refs., 4 figs.

  18. Chromosome walking on the TCL1 locus involved in T-cell neoplasia.

    PubMed Central

    Virgilio, L; Isobe, M; Narducci, M G; Carotenuto, P; Camerini, B; Kurosawa, N; Abbas-ar-Rushdi; Croce, C M; Russo, G

    1993-01-01

    The TCL1 locus on chromosome 14 band q32.1 is frequently involved in the chromosomal translocations and inversions with the T-cell receptor genes observed in several T-cell tumors, including T-prolymphocytic leukemias, acute and chronic leukemias associated with the immunodeficiency syndrome ataxia-telangiectasia, and adult T-cell leukemia. All breakpoints cloned in this area have been mapped to 14q32.1, an area distant approximately 10,000 kb from the immunoglobulin heavy-chain gene locus on chromosome 14q band 32.3. Except for two cases of inversion, no physical linkage of the cloned breakpoints has been reported, nor has a gene been identified in this region. Taking advantage of chromosome-walking techniques and of the P1 phage, we cloned and characterized 450 kb of the germ-line TCL1 locus, starting from the breakpoints of two independent T-cell leukemias. We show that all molecular rearrangements characterized so far map to these clones, indicating not only that this region is the target of chromosomal rearrangements occurring in this area but also that both inversion and translocations occur within a 300-kb region in the T-cell leukemias. In the attempt to identify a candidate oncogene responsible for the malignant transformation, a CpG island centromeric to the inversions and to the translocations has been identified. Two probes near the CpG island have detected sequences conserved among species, as well as two transcripts in the K562 human erythroleukemia cell line. On the basis of these data, a model of activation of the putative TCL1 oncogene is suggested. Images Fig. 2 Fig. 3 PMID:8415691

  19. 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

  20. Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15

    SciTech Connect

    Kohrman, D.C.; Plummer, N.W.; Schuster, T.

    1995-03-20

    Homozygous transgenic mice from line A4 have an early-onset progressive neuromuscular disorder characterized by paralysis of the rear limbs, muscle atrophy, and lethality by 4 weeks of age. The transgene insertion site was mapped to distal chromosome 15 close to the locus motor endplate disease (med). The sequence of mouse DNA flanking the insertion site junctions was determined. A small (<20 kb) deletion was detected at the insertion site, with no evidence of additional rearrangement of the chromosomal DNA. Noncomplementation of the transgene-induced mutation and med was demonstrated in a cross with med{sup J}/ + mice. The new allele is designated med{sup TgNA4Bs}(med{sup tg}). The homologous human locus MED was assigned to chromosome 12. Synaptotagmin 1 and contactin 1 were eliminated as candidate genes for the med mutation. The transgene-induced allele provides molecular access to the med gene, whose function is required for synaptic transmission at the neuromuscular junction and long-term survival of cerebellar Purkinje cells. 49 refs., 5 figs., 1 tab.

  1. A novel locus for autosomal dominant cone-rod dystrophy maps to chromosome 10q

    PubMed Central

    Kamenarova, Kunka; Cherninkova, Sylvia; Romero Durán, Margarita; Prescott, DeQuincy; Valdés Sánchez, Maria Lourdes; Mitev, Vanio; Kremensky, Ivo; Kaneva, Radka; Bhattacharya, Shomi S; Tournev, Ivailo; Chakarova, Christina

    2013-01-01

    Here we report recruitment of a three-generation Romani (Gypsy) family with autosomal dominant cone-rod dystrophy (adCORD). Involvement of known adCORD genes was excluded by microsatellite (STR) genotyping and linkage analysis. Subsequently, two independent total-genome scans using STR markers and single-nucleotide polymorphisms (SNPs) were performed. Haplotype analysis revealed a single 6.7-Mb novel locus between markers D10S1757 and D10S1782 linked to the disease phenotype on chromosome 10q26. Linkage analysis gave a maximum LOD score of 3.31 for five fully informative STR markers within the linked interval corresponding to the expected maximum in the family. Multipoint linkage analysis of SNP genotypes yielded a maximum parametric linkage score of 2.71 with markers located in the same chromosomal interval. There is no previously mapped CORD locus in this interval, and therefore the data reported here is novel and likely to identify a new gene that may eventually contribute to new knowledge on the pathogenesis of this condition. Sequencing of several candidate genes within the mapped interval led to negative findings in terms of the underlying molecular pathogenesis of the disease in the family. Analysis by comparative genomic hybridization excluded large chromosomal aberrations as causative of adCORD in the pedigree. PMID:22929024

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

    PubMed Central

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

    1990-01-01

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

  3. Evidence for chromosome fragility at the frataxin locus in Friedreich ataxia.

    PubMed

    Kumari, Daman; Hayward, Bruce; Nakamura, Asako J; Bonner, William M; Usdin, Karen

    2015-11-01

    Friedreich ataxia (FRDA) is a member of the Repeat Expansion Diseases, a group of genetic conditions resulting from an increase/expansion in the size of a specific tandem array. FRDA results from expansion of a GAA/TTC-tract in the first intron of the frataxin gene (FXN). The disease-associated tandem repeats all form secondary structures that are thought to contribute to the propensity of the repeat to expand. The subset of these diseases that result from a CGG/CCG-repeat expansion, such as Fragile X syndrome, also express a folate-sensitive fragile site coincident with the repeat on the affected chromosome. This chromosome fragility involves the generation of chromosome/chromatid gaps or breaks, or the high frequency loss of one or both copies of the affected gene when cells are grown under folate stress or as we showed previously, in the presence of an inhibitor of the ATM checkpoint kinase. Whether Repeat Expansion Disease loci containing different repeats form similar fragile sites was not known. We show here that the region of chromosome 9 that contains the FXN locus is intrinsically prone to breakage in vivo even in control cells. However, like FXS alleles, FRDA alleles show significantly elevated levels of chromosome abnormalities in the presence of an ATM inhibitor, consistent with the formation of a fragile site. PMID:26379101

  4. GSP-1 genes are linked to the grain hardness locus (Ha) on wheat chromosome 5D.

    PubMed Central

    Jolly, C J; Glenn, G M; Rahman, S

    1996-01-01

    An important determinant of wheat grain quality is the hardness of the grain. The trait is controlled by a major locus, Ha, on the short arm of chromosome 5D. Purified starch granules from soft-grained wheats have associated with them 15-kDa polypeptides called grain softness proteins (GSPs) or "friabilins." Genes that encode one family of closely related GSP polypeptides - GSP-1 genes - were mapped using chromosome substitution lines to the group 5 chromosomes. An F2 population segregating for hard and soft alleles at the Ha locus on a near-isogenic background was used in a single-seed study of the inheritance of grain softness and of GSP-1 alleles. Grain softness versus grain hardness was inherited in a 3:1 ratio. The presence versus absence of GSPs in single seed starch preparations was coinherited with grain softness versus hardness. This showed that grain softness is primarily determined by seed, and not by maternal, genotype. In addition, no recombination was detected in 44 F2 plants between GSP-1 restriction fragment length polymorphisms and Ha alleles. Differences between hard and soft wheat grains in membrane structure and lipid extractability have been described and, of the three characterized proteins that are part of the mixture of 15-kDa polypeptides called GSPs, at least two, and probably all three, are proteins that bind polar lipids. The data are interpreted to suggest that the Ha locus may encode one or more members of a large family of lipid-binding proteins. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:8637887

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

    PubMed

    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

  6. 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

  7. A novel locus for a hereditary recurrent neuropathy on chromosome 21q21.

    PubMed

    Calpena, E; Martínez-Rubio, D; Arpa, J; García-Peñas, J J; Montaner, D; Dopazo, J; Palau, F; Espinós, C

    2014-08-01

    Hereditary recurrent neuropathies are uncommon. Disorders with a known molecular basis falling within this group include hereditary neuropathy with liability to pressure palsies (HNPP) due to the deletion of the PMP22 gene or to mutations in this same gene, and hereditary neuralgic amyotrophy (HNA) caused by mutations in the SEPT9 gene. We report a three-generation family presenting a hereditary recurrent neuropathy without pathological changes in either PMP22 or SEPT9 genes. We performed a genome-wide mapping, which yielded a locus of 12.4 Mb on chromosome 21q21. The constructed haplotype fully segregated with the disease and we found significant evidence of linkage. After mutational screening of genes located within this locus, encoding for proteins and microRNAs, as well as analysis of large deletions/insertions, we identified 71 benign polymorphisms. Our findings suggest a novel genetic locus for a recurrent hereditary neuropathy of which the molecular defect remains elusive. Our results further underscore the clinical and genetic heterogeneity of this group of neuropathies. PMID:24878226

  8. Novel Locus for Paroxysmal Kinesigenic Dyskinesia Mapped to Chromosome 3q28-29

    PubMed Central

    Liu, Ding; Zhang, Yumiao; Wang, Yu; Chen, Chanjuan; Li, Xin; Zhou, Jinxia; Song, Zhi; Xiao, Bo; Rasco, Kevin; Zhang, Feng; Wen, Shu; Li, Guoliang

    2016-01-01

    Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent and brief attacks of dystonia or chorea precipitated by sudden movements. It can be sporadic or familial. Proline-Rich Transmembrane Protein 2 (PRRT2) has been shown to be a common causative gene of PKD. However, less than 50% of patients with primary PKD harbor mutations in PRRT2. The aim of this study is to use eight families with PKD to identify the pathogenic PRRT2 mutations, or possible novel genetic cause of PKD phenotypes. After extensive clinical investigation, direct sequencing and mutation analysis of PRRT2 were performed on patients from eight PKD families. A genome-wide STR and SNP based linkage analysis was performed in one large family that is negative for pathogenic PRRT2 mutations. Using additional polymorphic markers, we identified a novel gene locus on chromosome 3q in this PRRT2-mutation-negative PKD family. The LOD score for the region between markers D3S1314 and D3S1256 is 3.02 and we proposed to designate this locus as Episodic Kinesigenic Dyskinesia (EKD3). Further studies are needed to identify the causative gene within this locus. PMID:27173777

  9. Novel Locus for Paroxysmal Kinesigenic Dyskinesia Mapped to Chromosome 3q28-29.

    PubMed

    Liu, Ding; Zhang, Yumiao; Wang, Yu; Chen, Chanjuan; Li, Xin; Zhou, Jinxia; Song, Zhi; Xiao, Bo; Rasco, Kevin; Zhang, Feng; Wen, Shu; Li, Guoliang

    2016-01-01

    Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent and brief attacks of dystonia or chorea precipitated by sudden movements. It can be sporadic or familial. Proline-Rich Transmembrane Protein 2 (PRRT2) has been shown to be a common causative gene of PKD. However, less than 50% of patients with primary PKD harbor mutations in PRRT2. The aim of this study is to use eight families with PKD to identify the pathogenic PRRT2 mutations, or possible novel genetic cause of PKD phenotypes. After extensive clinical investigation, direct sequencing and mutation analysis of PRRT2 were performed on patients from eight PKD families. A genome-wide STR and SNP based linkage analysis was performed in one large family that is negative for pathogenic PRRT2 mutations. Using additional polymorphic markers, we identified a novel gene locus on chromosome 3q in this PRRT2-mutation-negative PKD family. The LOD score for the region between markers D3S1314 and D3S1256 is 3.02 and we proposed to designate this locus as Episodic Kinesigenic Dyskinesia (EKD3). Further studies are needed to identify the causative gene within this locus. PMID:27173777

  10. Evidence against a second autosomal dominant retinitis pigmentosa locus close to rhodopsin on chromosome 3q

    SciTech Connect

    Inglehearn, C.; Bhattacharya, S. ); Farrar, J.; Humphries, P. ); Denton, M. ); Gal, A. )

    1993-08-01

    In 1989 McWilliam et al. reported close linkage of the autosomal dominant retinitis pigmentosa (adRP) locus to chromosome 3q marker D3S47 in a large Irish pedigree (McWilliam et al 1989). Subsequent studies confirmed linkage in two other adRP families (Lester et al 1990; Olsson et al. 1990). Shortly afterward, utations in the rhodopsin (RHO) gene, mapping to 3q21-24, were implicated in disease causation, and it is now known that around one-third of adRP results from such mutations (Dryja et al. 1991; Sung et al. 1991; Inglchearn et al. 1992a). At that time, sequencing studies had failed to find rhodopsin mutations in the three families first linked to 3q. Several adRP families in which rhodopsin mutations had been found gave lod scores that, when pooled, had a peak of 4.47 at a theta of .12 (Inglehearn et al. 1992b). The apparent lack of mutations in families TCDM1, adRP3, and 20 together with the linkage data in these and the proved RHO-RP families, led to speculation that two adRP loci existed on chromosome 3q (Olsson et al. 1990; Inglehearn et al. 1992b). However this situation has been reversed by more recent analysis, since rhodopsin mutations have now been found in all three families. There is therefore no longer any evidence to support the hypothesis that a second adRP locus exists close to rhodopsin on chromosome 3q.

  11. 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.

  12. 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

  13. Fine mapping of the chromosome 3p susceptibility locus in inflammatory bowel disease

    PubMed Central

    Hampe, J; Lynch, N; Daniels, S; Bridger, S; Macpherson, A; Stokkers, P; Forbes, A; Lennard-Jones, J; Mathew, C; Curran, M; Schreiber, S

    2001-01-01

    BACKGROUND AND AIMS—Genetic predisposition for inflammatory bowel disease (IBD) has been demonstrated by epidemiological and genetic linkage studies. Genetic linkage of IBD to chromosome 3 has been observed previously. A high density analysis of chromosome 3p was performed to confirm prior linkages and elucidate potential genetic associations.
METHODS—Forty three microsatellite markers on chromosome 3 were genotyped in 353 affected sibling pairs of North European Caucasian extraction (average marker density 2 cM in the linkage interval). Marker order was defined by genetic and radiation hybrid techniques.
RESULTS—The maximum single point logarithm of odds (LOD) score was observed for Crohn's disease at D3S3591. Peak multipoint LOD scores of 1.65 and 1.40 for the IBD phenotype were observed near D3S1304 (distal 3p) and near D3S1283 in the linkage region previously reported. Crohn's disease contributed predominantly to the linkage. The transmission disequilibrium test showed significant evidence of association (p=0.009) between allele 4 of D3S1076 and the IBD phenotype (51 transmitted v 28 non-transmitted). Two known polymorphisms in the CCR2 and CCR5 genes were analysed, neither of which showed significant association with IBD. Additional haplotype associations were observed in the vicinity of D3S1076.
CONCLUSIONS—This study provides confirmatory linkage evidence for an IBD susceptibility locus on chromosome 3p and suggests that CCR2 and CCR5 are unlikely to be major susceptibility loci for IBD. The association findings in this region warrant further investigation.


Keywords: inflammatory bowel disease; fine mapping; chromosome 3 PMID:11156639

  14. Definition of a tumor suppressor locus within human chromosome 3p21-p22.

    PubMed Central

    Killary, A M; Wolf, M E; Giambernardi, T A; Naylor, S L

    1992-01-01

    Cytogenetic abnormalities and high-frequency allele losses involving the short arm of human chromosome 3 have been identified in a variety of histologically different neoplasms. These findings suggest that a tumor-suppressor gene or genes may be located in the region of 3p14-p25, although there has been no definitive functional proof for the involvement of a particular region of 3p. We report a rapid genetic assay system that has allowed functional analysis of defined regions of 3p in the suppression of tumorigenicity in vivo. Interspecific microcell hybrids containing fragments of chromosome 3p were constructed and screened for tumorigenicity in athymic nude mice. Hybrid clones were obtained that showed a dramatic tumor suppression and contained a 2-megabase fragment of human chromosomal material encompassing the region 3p21 near the interface with 3p22. With these hybrid clones, we have defined a genetic locus at 3p21-p22 intimately involved in tumor suppression. Images PMID:1438292

  15. 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.

  16. 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.

  17. A locus for autosomal dominant colobomatous microphthalmia maps to chromosome 15q12-q15.

    PubMed

    Morlé, L; Bozon, M; Zech, J C; Alloisio, N; Raas-Rothschild, A; Philippe, C; Lambert, J C; Godet, J; Plauchu, H; Edery, P

    2000-12-01

    Congenital microphthalmia is a common developmental ocular disorder characterized by shortened axial length. Isolated microphthalmia is clinically and genetically heterogeneous and may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Here, we studied a five-generation family of Sephardic Jewish origin that included 38 members, of whom 7 have either unilateral or bilateral microphthalmia of variable severity inherited as an autosomal dominant trait with incomplete penetrance. After exclusion of several candidate loci, we performed a genome-scan study and demonstrated linkage to chromosome 15q12-q15. Positive LOD scores were obtained with a maximum at the D15S1007 locus (maximum LOD score 3.77, at recombination fraction 0.00). Haplotype analyses supported the location of the disease-causing gene in a 13.8-cM interval between loci D15S1002 and D15S1040. PMID:11035633

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

    PubMed

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

    2012-01-01

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

  19. 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

  20. 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.

  1. A Susceptibility Locus for Migraine with Aura, on Chromosome 4q24

    PubMed Central

    Wessman, Maija; Kallela, Mikko; Kaunisto, Mari A.; Marttila, Pia; Sobel, Eric; Hartiala, Jaana; Oswell, Greg; Leal, Suzanne M.; Papp, Jeanette C.; Hämäläinen, Eija; Broas, Petra; Joslyn, Geoffrey; Hovatta, Iiris; Hiekkalinna, Tero; Kaprio, Jaakko; Ott, Jürg; Cantor, Rita M.; Zwart, John-Anker; Ilmavirta, Matti; Havanka, Hannele; Färkkilä, Markus; Peltonen, Leena; Palotie, Aarno

    2002-01-01

    Migraine is a complex neurovascular disorder with substantial evidence supporting a genetic contribution. Prior attempts to localize susceptibility loci for common forms of migraine have not produced conclusive evidence of linkage or association. To date, no genomewide screen for migraine has been published. We report results from a genomewide screen of 50 multigenerational, clinically well-defined Finnish families showing intergenerational transmission of migraine with aura (MA). The families were screened using 350 polymorphic microsatellite markers, with an average intermarker distance of 11 cM. Significant evidence of linkage was found between the MA phenotype and marker D4S1647 on 4q24. Using parametric two-point linkage analysis and assuming a dominant mode of inheritance, we found for this marker a maximum LOD score of 4.20 under locus homogeneity (P=.000006) or locus heterogeneity (P=.000011). Multipoint parametric (HLOD = 4.45; P=.0000058) and nonparametric (NPLall = 3.43; P=.0007) analyses support linkage in this region. Statistically significant linkage was not observed in any other chromosomal region. PMID:11836652

  2. 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

  3. 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.

  4. 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.

  5. Fine Mapping of the Barley Chromosome 6H Net Form Net Blotch Susceptibility Locus

    PubMed Central

    Richards, Jonathan; Chao, Shiaoman; Friesen, Timothy; Brueggeman, Robert

    2016-01-01

    Net form net blotch, caused by the necrotrophic fungal pathogen Pyrenophora teres f. teres, is a destructive foliar disease of barley with the potential to cause significant yield loss in major production regions throughout the world. The complexity of the host–parasite genetic interactions in this pathosystem hinders the deployment of effective resistance in barley cultivars, warranting a deeper understanding of the interactions. Here, we report on the high-resolution mapping of the dominant susceptibility locus near the centromere of chromosome 6H in the barley cultivars Rika and Kombar, which are putatively targeted by necrotrophic effectors from P. teres f. teres isolates 6A and 15A, respectively. Utilization of progeny isolates derived from a cross of P. teres f. teres isolates 6A × 15A harboring single major virulence loci (VK1, VK2, and VR2) allowed for the Mendelization of single inverse gene-for-gene interactions in a high-resolution population consisting of 2976 Rika × Kombar recombinant gametes. Brachypodium distachyon synteny was exploited to develop and saturate the susceptibility region with markers, delimiting it to ∼0.24 cM and a partial physical map was constructed. This genetic and physical characterization further resolved the dominant susceptibility locus, designated Spt1 (susceptibility to P. teres f. teres). The high-resolution mapping and cosegregation of the Spt1.R and Spt1.K gene/s indicates tightly linked genes in repulsion or alleles possibly targeted by different necrotrophic effectors. Newly developed barley genomic resources greatly enhance the efficiency of positional cloning efforts in barley, as demonstrated by the Spt1 fine mapping and physical contig identification reported here. PMID:27172206

  6. Fine Mapping of the Barley Chromosome 6H Net Form Net Blotch Susceptibility Locus.

    PubMed

    Richards, Jonathan; Chao, Shiaoman; Friesen, Timothy; Brueggeman, Robert

    2016-01-01

    Net form net blotch, caused by the necrotrophic fungal pathogen Pyrenophora teres f. teres, is a destructive foliar disease of barley with the potential to cause significant yield loss in major production regions throughout the world. The complexity of the host-parasite genetic interactions in this pathosystem hinders the deployment of effective resistance in barley cultivars, warranting a deeper understanding of the interactions. Here, we report on the high-resolution mapping of the dominant susceptibility locus near the centromere of chromosome 6H in the barley cultivars Rika and Kombar, which are putatively targeted by necrotrophic effectors from P. teres f. teres isolates 6A and 15A, respectively. Utilization of progeny isolates derived from a cross of P. teres f. teres isolates 6A × 15A harboring single major virulence loci (VK1, VK2, and VR2) allowed for the Mendelization of single inverse gene-for-gene interactions in a high-resolution population consisting of 2976 Rika × Kombar recombinant gametes. Brachypodium distachyon synteny was exploited to develop and saturate the susceptibility region with markers, delimiting it to ∼0.24 cM and a partial physical map was constructed. This genetic and physical characterization further resolved the dominant susceptibility locus, designated Spt1 (susceptibility to P. teres f. teres). The high-resolution mapping and cosegregation of the Spt1.R and Spt1.K gene/s indicates tightly linked genes in repulsion or alleles possibly targeted by different necrotrophic effectors. Newly developed barley genomic resources greatly enhance the efficiency of positional cloning efforts in barley, as demonstrated by the Spt1 fine mapping and physical contig identification reported here. PMID:27172206

  7. Muscular dystrophy in an X; 1 translocation female suggests that Duchenne locus is on X chromosome short arm.

    PubMed Central

    Lindenbaum, R H; Clarke, G; Patel, C; Moncrieff, M; Hughes, J T

    1979-01-01

    A unique combination of a Duchenne-like muscular dystrophy in a girl with a translocation-inversion rearrangement involving an X chromosome and a no 1 chromosome appeared as a result of both gene mutation and chromosome mutation in the mother. The X-autosome rearrangement would permit full expression of an X-linked recessive gene, such as that for Duchenne muscular dystrophy, in a female, and this would satisfactorily explain the characteristic Duchenne-like course of our patient's illness. The simultaneous de novo appearance of the Duchenne mutation and the X;1 rearrange suggests possible sites for the Duchenne locus on the X chromosome short arm (at Xp1106 or Xp2107). Images PMID:513085

  8. ROSTROVENTRAL CAUDATE PUTAMEN INVOLVEMENT IN ETHANOL WITHDRAWAL IS INFLUENCED BY A CHROMOSOME 4 LOCUS

    PubMed Central

    Chen, G.; Buck, K.J.

    2010-01-01

    Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains alcohol use and abuse and may contribute to relapse in dependent individuals. Although no animal model duplicates alcoholism, models for specific factors, like withdrawal, are useful for identifying potential genetic and neural determinants of liability in humans. Previously, we identified a quantitative trait locus (QTL) and gene (Mpdz, which encodes the multi-PDZ domain protein) on chromosome 4 with a large effect on alcohol withdrawal in mice. Using congenic mice that confirm this QTL and c-Fos expression as a high-resolution marker of neuronal activation, we report that congenic mice demonstrate significantly less neuronal activity associated with alcohol withdrawal in the rostroventral caudate putamen (rvCP), but not other parts of the striatum, compared with background strain mice. Moreover, bilateral rvCP lesions significantly increase alcohol withdrawal severity. Using retrograde (fluorogold) and anterograde (Texas Red conjugated dextran amine) tract tracing, we found that ~25% of c-Fos immunoreactive rvCP neurons project to caudolateral substantia nigra pars reticulata (clSNr), which we previously found is crucially involved in withdrawal following acute and repeated alcohol exposure. Our results expand upon work suggesting that this QTL impacts alcohol withdrawal via basal ganglia circuitry associated with limbic function, and indicate that an rvCP-clSNr projection plays a critical role. Given the growing body of evidence that the syntenic region of human chromosome 9p and MPDZ are associated with alcohol abuse, our results may facilitate research on alcohol dependence and associated withdrawal in clinical populations. PMID:20608999

  9. 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.

  10. A new locus for autosomal dominant retinitis pigmentosa on the short arm of chromosome 17.

    PubMed

    Greenberg, J; Goliath, R; Beighton, P; Ramesar, R

    1994-06-01

    Retinitis pigmentosa (RP) is a group of genetically and clinically heterogeneous retinopathies, some of which have been shown to result from mutations in two different known retinal genes, rhodopsin (3q) and peripherin-rds (6p). Three additional anonymous loci at 7p, 7q and pericentric 8 have been implicated by linkage studies. There are still, however, a few families in which all known loci have been excluded. In this report we present data indicating a location, on the short arm of chromosome 17, for the autosomal dominant RP (ADRP) locus in a large South African (SA) family of British ancestry. Positive two-point lod scores have been obtained for nine markers (D17S938, Z = 5.43; D17S796, Z = 4.82; D17S849, Z = 3.6; D17S786, Z = 3.55; TP53, Z = 3.55; D17S578, Z = 3.29; D17S960, Z = 3.16; D17S926, Z = 1.51; D17S804, Z = 0.47 all at theta = 0.10 except D17S804 and D17S926, theta = 0.20). These data provide definitive evidence for the localization of an ADRP gene on chromosome 17p. The human recoverin gene has been localized to 17p13.1 and was consequently a prime candidate for ADRP in the family studied. However, mutation screening of the three exons of this gene failed to produce any evidence of recoverin being the gene involved in the pathogenesis of ADRP in this SA family. PMID:7951236

  11. Identification of a lupus-susceptibility locus leading to impaired clearance of apoptotic debris on New Zealand Black chromosome 13

    PubMed Central

    Pau, Evelyn; Loh, Christina; Minty, Gillian E.S.; Chang, Nan-Hua; Wither, Joan E.

    2016-01-01

    Systemic lupus erythematosus is a chronic multi-organ autoimmune disease marked mainly by the production of anti-nuclear antibodies. Nuclear antigens become accessible to the immune system following apoptosis and defective clearance of apoptotic debris has been shown in several knockout mouse models to promote lupus. However, genetic loci associated with defective clearance are not well defined in spontaneously arising lupus models. We previously showed that introgression of the chromosome 13 interval from lupus-prone New Zealand Black (NZB) mice onto a non-autoimmune B6 genetic background (B6.NZBc13) recapitulated many of the NZB autoimmune phenotypes. Here, we show that B6.NZBc13 mice have impaired clearance of apoptotic debris by peritoneal and tingible-body macrophages and have narrowed down the chromosomal interval of this defect using subcongenic mice with truncated NZB chromosome 13 intervals. This chromosomal region (81–94 Mb) is sufficient to produce polyclonal B and T cell activation, and expansion of dendritic cells. To fully recapitulate the autoimmune phenotypes seen in B6.NZBc13 mice, at least one additional locus located in the centromeric portion of the interval is required. Thus, we have identified a novel lupus susceptibility locus on NZB chromosome 13 that is associated with impaired clearance of apoptotic debris. PMID:23328841

  12. 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.

  13. 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.

  14. Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q

    SciTech Connect

    Kwon, J.M.; Elliott, J.L.; Yee, W.C.

    1995-10-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. The neuronal form of this disorder is referred to as Charcot-Marie-Tooth type II disease (CMT2). CMT2 is usually inherited as an autosomal dominant trait with a variable age at onset of symptoms associated with progressive axonal neuropathy. In some families, the locus that predisposes to CMT2 has been demonstrated to map to the distal portion of the short arm of chromosome 1. Other families with CMT2 do not show linkage with 1p markers, suggesting genetic heterogeneity in CMT2. We investigated linkage in a single large kindred with autosomal dominant CMT2. The gene responsible for CMT2 in this kindred (CMT2B) was mapped to the interval between the microsatellite markers D3S1769 and D3S1744 in the 3q13-22 region. Study of additional CMT2 kindreds should serve to further refine the disease gene region and may ultimately lead to the identification of a gene defect that underlies the CMT2 phenotype. 21 refs., 3 figs., 1 tab.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. A bacterial artificial chromosome contig spanning the major domestication locus Q in wheat and identification of a candidate gene.

    PubMed Central

    Faris, Justin D; Fellers, John P; Brooks, Steven A; Gill, Bikram S

    2003-01-01

    The Q locus played a major role in the domestication of wheat because it confers the free-threshing character and influences many other agronomically important traits. We constructed a physical contig spanning the Q locus using a Triticum monococcum BAC library. Three chromosome walking steps were performed by complete sequencing of BACs and identification of low-copy markers through similarity searches of database sequences. The BAC contig spans a physical distance of approximately 300 kb corresponding to a genetic distance of 0.9 cM. The physical map of T. monococcum had perfect colinearity with the genetic map of wheat chromosome arm 5AL. Recombination data in conjunction with analysis of fast neutron deletions confirmed that the contig spanned the Q locus. The Q gene was narrowed to a 100-kb segment, which contains an APETALA2 (AP2)-like gene that cosegregates with Q. AP2 is known to play a major role in controlling floral homeotic gene expression and thus is an excellent candidate for Q. PMID:12750342

  1. Mapping of DNA markers linked to the cystic fibrosis locus on the long arm of chromosome 7.

    PubMed Central

    Zengerling, S; Tsui, L C; Grzeschik, K H; Olek, K; Riordan, J R; Buchwald, M

    1987-01-01

    We have used a panel of eight human/mouse somatic-cell hybrids, each containing various portions of human chromosome 7, and three patient cell lines with interstitial deletions on chromosome 7 for localization of six DNA markers linked to the cystic fibrosis locus. Our data suggest that D7S15 is located in the region 7 cen----q22, that MET is located in 7q22----31, and that D7S8 and 7C22 are located in q22----q32. The hybridization results for COL1A2 and TCRB are consistent with their previous assignment to 7q21----q22 and 7q32, respectively. Given the location of these six markers and their linkage relationships, it is probable that the cystic fibrosis locus is in either the distal region of band q22 or the proximal region of q31. Using the same set of cell lines, we have also examined the location of another chromosome 7 marker PGY1. The data show that PGY1 is located in the region 7cen----q22, a position very different from its previous assignment. Images Fig. 1 PMID:3472464

  2. 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.

  3. 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

  4. 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.

  5. 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

  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. 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.

  8. 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).

  9. 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

  10. Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus

    PubMed Central

    Labbé, Catherine; Ogaki, Kotaro; Lorenzo-Betancor, Oswaldo; Carrasquillo, Minerva M.; Heckman, Michael G.; McCarthy, Allan; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Dickson, Dennis W.; Uitti, Ryan J.; Wszolek, Zbigniew K.; Ross, Owen A.

    2015-01-01

    Genome-wide association studies (GWAS) in Parkinson’s disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11–1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD. PMID:26090850

  11. Synteny perturbations between wheat homoeologous chromosomes caused by locus duplications and deletions correlate with recombination rates

    PubMed Central

    Akhunov, Eduard D.; Akhunova, Alina R.; Linkiewicz, Anna M.; Dubcovsky, Jorge; Hummel, David; Lazo, Gerry; Chao, Shiaoman; Anderson, Olin D.; David, Jacques; Qi, Lili; Echalier, Benjamin; Gill, Bikram S.; Miftahudin; Gustafson, J. Perry; La Rota, Mauricio; Sorrells, Mark E.; Zhang, Deshui; Nguyen, Henry T.; Kalavacharla, Venugopal; Hossain, Khwaja; Kianian, Shahryar F.; Peng, Junhua; Lapitan, Nora L. V.; Wennerlind, Emily J.; Nduati, Vivienne; Anderson, James A.; Sidhu, Deepak; Gill, Kulvinder S.; McGuire, Patrick E.; Qualset, Calvin O.; Dvorak, Jan

    2003-01-01

    Loci detected by Southern blot hybridization of 3,977 expressed sequence tag unigenes were mapped into 159 chromosome bins delineated by breakpoints of a series of overlapping deletions. These data were used to assess synteny levels along homoeologous chromosomes of the wheat A, B, and D genomes, in relation to both bin position on the centromere-telomere axis and the gradient of recombination rates along chromosome arms. Synteny level decreased with the distance of a chromosome region from the centromere. It also decreased with an increase in recombination rates along the average chromosome arm. There were twice as many unique loci in the B genome than in the A and D genomes, and synteny levels between the B genome chromosomes and the A and D genome homoeologues were lower than those between the A and D genome homoeologues. These differences among the wheat genomes were attributed to differences in the mating systems of wheat diploid ancestors. Synteny perturbations were characterized in 31 paralogous sets of loci with perturbed synteny. Both insertions and deletions of loci were detected and both preferentially occurred in high recombination regions of chromosomes. PMID:12960374

  12. 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

  13. 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

  14. Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17

    PubMed Central

    Peden, John F; Olsson, Per G; Clarke, Robert; Hellenius, Mai-Lis; Rust, Stephan; Lagercrantz, Jacob; Franzosi, Maria Grazia; Schulte, Helmut; Carey, Alisoun; Olsson, Gunnar; Assmann, Gerd; Tognoni, Gianni; Collins, Rory; Hamsten, Anders; Watkins, Hugh

    2006-01-01

    Coronary artery disease (CAD) is a leading cause of death world-wide, and most cases have a complex, multifactorial aetiology that includes a substantial heritable component. Identification of new genes involved in CAD may inform pathogenesis and provide new therapeutic targets. The PROCARDIS study recruited 2,658 affected sibling pairs (ASPs) with onset of CAD before age 66 y from four European countries to map susceptibility loci for CAD. ASPs were defined as having CAD phenotype if both had CAD, or myocardial infarction (MI) phenotype if both had a MI. In a first study, involving a genome-wide linkage screen, tentative loci were mapped to Chromosomes 3 and 11 with the CAD phenotype (1,464 ASPs), and to Chromosome 17 with the MI phenotype (739 ASPs). In a second study, these loci were examined with a dense panel of grid-tightening markers in an independent set of families (1,194 CAD and 344 MI ASPs). This replication study showed a significant result on Chromosome 17 (MI phenotype; p = 0.009 after adjustment for three independent replication tests). An exclusion analysis suggests that further genes of effect size λsib > 1.24 are unlikely to exist in these populations of European ancestry. To our knowledge, this is the first genome-wide linkage analysis to map, and replicate, a CAD locus. The region on Chromosome 17 provides a compelling target within which to identify novel genes underlying CAD. Understanding the genetic aetiology of CAD may lead to novel preventative and/or therapeutic strategies. PMID:16710446

  15. 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.

  16. Linkage Disequilibrium on the Bovine X Chromosome: Characterization and Use in Quantitative Trait Locus Mapping

    PubMed Central

    Sandor, Cynthia; Farnir, Frédéric; Hansoul, Sarah; Coppieters, Wouter; Meuwissen, Théo; Georges, Michel

    2006-01-01

    We herein demonstrate that in the Holstein–Friesian dairy cattle population, microsatellites are as polymorphic on the X chromosome as on the autosomes but that the level of linkage disequilibrium between these markers is higher on the X chromosome than on the autosomes. The latter observation is not compatible with the small male-to-female ratio that prevails in this population and results in a higher gonosomal than autosomal effective population size. It suggests that the X chromosome undergoes distinct selective or mutational forces. We describe and characterize a novel Markovian approach to exploit this linkage disequilibrium to compute the probability that two chromosomes are identical-by-descent conditional on flanking marker data. We use the ensuing probabilities in a restricted maximum-likelihood approach to search for quantitative trait loci (QTL) affecting 48 traits of importance to the dairy industry and provide evidence for the presence of QTL affecting 5 of these traits on the bovine X chromosome. PMID:16648641

  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. Chromosomal locus rearrangements are a rapid response to formation of the allotetraploid Arabidopsis suecica genome

    PubMed Central

    Pontes, Olga; Neves, Nuno; Silva, Manuela; Lewis, Michelle S.; Madlung, Andreas; Comai, Luca; Viegas, Wanda; Pikaard, Craig S.

    2004-01-01

    Allopolyploidy is a significant evolutionary process, resulting in new species with diploid or greater chromosome complements derived from two or more progenitor species. We examined the chromosomal consequences of genomic merger in Arabidopsis suecica, the allotetraploid hybrid of Arabidopsis thaliana and Arabidopsis arenosa. Fluorescence in situ hybridization with centromere, nucleolus organizer region (NOR), and 5S rRNA gene probes reveals the expected numbers of progenitor chromosomes in natural A. suecica, but one pair of A. thaliana NORs and one pair of A. arenosa-derived 5S gene loci are missing. Similarly, in newly formed synthetic A. suecica-like allotetraploids, pairs of A. thaliana NORs are gained de novo, lost, and/or transposed to A. arenosa chromosomes, with genotypic differences apparent between F3 siblings of the same F2 parent and between independent lines. Likewise, pairs of A. arenosa 5S genes are lost and novel linkages between 5S loci and NORs arise in synthetic allotetraploids. By contrast, the expected numbers of A. arenosa-derived NORs and A. thaliana-derived 5S loci are found in both natural and synthetic A. suecica. Collectively, these observations suggest that some, but not all, loci are unstable in newly formed A. suecica allotetraploids and can participate in a variety of alternative rearrangements, some of which resemble chromosomal changes found in nature. PMID:15604143

  19. Chromosomal locus rearrangements are a rapid response to formation of the allotetraploid Arabidopsis suecica genome.

    PubMed

    Pontes, Olga; Neves, Nuno; Silva, Manuela; Lewis, Michelle S; Madlung, Andreas; Comai, Luca; Viegas, Wanda; Pikaard, Craig S

    2004-12-28

    Allopolyploidy is a significant evolutionary process, resulting in new species with diploid or greater chromosome complements derived from two or more progenitor species. We examined the chromosomal consequences of genomic merger in Arabidopsis suecica, the allotetraploid hybrid of Arabidopsis thaliana and Arabidopsis arenosa. Fluorescence in situ hybridization with centromere, nucleolus organizer region (NOR), and 5S rRNA gene probes reveals the expected numbers of progenitor chromosomes in natural A. suecica, but one pair of A. thaliana NORs and one pair of A. arenosa-derived 5S gene loci are missing. Similarly, in newly formed synthetic A. suecica-like allotetraploids, pairs of A. thaliana NORs are gained de novo, lost, and/or transposed to A. arenosa chromosomes, with genotypic differences apparent between F(3) siblings of the same F(2) parent and between independent lines. Likewise, pairs of A. arenosa 5S genes are lost and novel linkages between 5S loci and NORs arise in synthetic allotetraploids. By contrast, the expected numbers of A. arenosa-derived NORs and A. thaliana-derived 5S loci are found in both natural and synthetic A. suecica. Collectively, these observations suggest that some, but not all, loci are unstable in newly formed A. suecica allotetraploids and can participate in a variety of alternative rearrangements, some of which resemble chromosomal changes found in nature. PMID:15604143

  20. Linkage disequilibrium on the bovine X chromosome: characterization and use in quantitative trait locus mapping.

    PubMed

    Sandor, Cynthia; Farnir, Frédéric; Hansoul, Sarah; Coppieters, Wouter; Meuwissen, Théo; Georges, Michel

    2006-07-01

    We herein demonstrate that in the Holstein-Friesian dairy cattle population, microsatellites are as polymorphic on the X chromosome as on the autosomes but that the level of linkage disequilibrium between these markers is higher on the X chromosome than on the autosomes. The latter observation is not compatible with the small male-to-female ratio that prevails in this population and results in a higher gonosomal than autosomal effective population size. It suggests that the X chromosome undergoes distinct selective or mutational forces. We describe and characterize a novel Markovian approach to exploit this linkage disequilibrium to compute the probability that two chromosomes are identical-by-descent conditional on flanking marker data. We use the ensuing probabilities in a restricted maximum-likelihood approach to search for quantitative trait loci (QTL) affecting 48 traits of importance to the dairy industry and provide evidence for the presence of QTL affecting 5 of these traits on the bovine X chromosome. PMID:16648641

  1. 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.

  2. 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.

  3. A YAC contig spanning the dominant retinitis pigmentosa locus (RP9) on chromosome 7p

    SciTech Connect

    Keen, T.J.; Inglehearn, C.F.; Patel, R.J.; Peacock, R.E.

    1995-08-10

    The dominant retinitis pigmentosa locus RP9 has previously been localized to 7p13-p15, in the interval D7S526-D7S484. We now report refinement of the locus to the interval D7S795-D7S484 and YAC contig of approximately 4.8 Mb spanning this region and extending both distally and proximally from it. The contig was constructed by STS content mapping and physically orders 29 STSs in 28 YAC clones. The order of polymorphic markers in the contig is consistent with a genetic map that has been assembled using haplotype data from the CEPH pedigrees. This contig will provide a primary resource for the construction of a transcriptional map of this region and for the identification of the defective gene causing this form of adRP. 27 refs., 3 figs., 1 tab.

  4. A New Locus on Chromosome 12p13.3 for Pseudohypoaldosteronism Type II, an Autosomal Dominant Form of Hypertension

    PubMed Central

    Disse-Nicodème, Sandra; Achard, Jean-Michel; Desitter, Isabelle; Houot, Anne-Marie; Fournier, Albert; Corvol, Pierre; Jeunemaitre, Xavier

    2000-01-01

    Pseudohypoaldosteronism type II (PHA2) is a rare autosomal dominant form of volume-dependent low-renin hypertension characterized by hyperkalemia and hyperchloremic acidosis but also by a normal glomerular filtration rate. These features, together with the correction of blood pressure and metabolic abnormalities by small doses of thiazide diuretics, suggest a primary renal tubular defect. Two loci have previously been mapped at low resolution to chromosome 1q31-42 (PHA2A) and 17p11-q21 (PHA2B). We have now analyzed a new, large French pedigree, in which 12 affected members over three generations confirmed the autosomal dominant inheritance. Affected subjects had hypertension together with long-term hyperkalemia (range 5.2–6.2 mmol/liter), hyperchloremia (range: 100-109 mmol/liter), normal plasma creatinine (range: 63–129 mmol/liter) and low renin levels. Genetic linkage was excluded for both PHA2A and PHA2B loci (all LOD scores Z<-3.2 at recombination fraction [θ] 0), as well as for the thiazide-sensitive sodium-chloride cotransporter gene. A genome-wide scan using 383 microsatellite markers showed a strong linkage with the chromosome 12p13 region (maximum LOD score Z=6.18, θ=0, at D12S99). Haplotype analysis using 10 additional polymorphic markers led to a minimum 13-cM interval flanked by D12S1652 and D12S336, thus defining a new PHA2C locus. Analysis of two obvious candidate genes (SCNN1A and GNb3) located within the interval showed no deleterious mutation. In conclusion, we hereby demonstrate further genetic heterogeneity of this Mendelian form of hypertension and identify a new PHA2C locus, the most compelling and precise linkage interval described to date. PMID:10869238

  5. 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.

  6. 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.

  7. 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.

  8. 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. PMID:25894238

  9. Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome.

    PubMed Central

    Davies, K E; Pearson, P L; Harper, P S; Murray, J M; O'Brien, T; Sarfarazi, M; Williamson, R

    1983-01-01

    The inheritance of two restriction fragment length polymorphisms (RFLPs) on the short arm of the human X chromosome has been studied relative to Duchenne muscular dystrophy. This provides a partial genetic map of the short arm of the human X chromosome between Xp110 and Xp223. The data were derived from the segregation between a RFLP located at Xp21-Xp223, the DMD locus, and a RFLP located at Xp110-Xp113. The genetic distance from Xp110 to Xp223 was found to be approximately 40 centimorgans (cM). This provides experimental confirmation that 1cM corresponds to approximately 1,000 kilobase pairs of DNA for this region of the human X chromosome. Our data confirm that the DMD mutation lies between Xp223 and Xp110. The availability of flanking probes surrounding the DMD locus will assist in the ordering of further DNA sequences relative to the mutation. Images PMID:6304647

  10. Mapping of a quantitative trait locus for beef marbling on bovine chromosome 9 in purebred Japanese black cattle.

    PubMed

    Imai, K; Matsughige, T; Watanabe, T; Sugimoto, Y; Ihara, N

    2007-01-01

    The goal of this study is to detect quantitative trait loci (QTL) for carcass traits applicable for a DNA-based breeding system in a Japanese Black cattle population. A purebred paternal half-sib family from a commercial line composed of 65 steers was initially analyzed using 188 informative microsatellites giving a 16-cM average interval covering 29 autosomes. A significant QTL for marbling was detected in the centromeric portion of bovine chromosome (BTA) 9. After additional marker genotyping across a larger sample size composed of 169 individuals, this locus was refined to a 20-cM confidence interval between microsatellites BM1227 (24 cM) and DIK2741 (50 cM) at a 1% chromosome-wise threshold. The allele substitution effect between Q and q for a beef marbling standard score (1 to 12 range) on BTA9 was 1.0 (5.7% of total phenotypic variance in QTL contribution in this family). This result provides a primary platform for a marker-assisted selection system of the beef marbling trait within the Japanese Black (Wagyu) cattle population. PMID:17453646

  11. A Scan of Chromosome 10 Identifies a Novel Locus Showing Strong Association with Late-Onset Alzheimer Disease

    PubMed Central

    Grupe, Andrew; Li, Yonghong; Rowland, Charles; Nowotny, Petra; Hinrichs, Anthony L.; Smemo, Scott; Kauwe, John S. K.; Maxwell, Taylor J.; Cherny, Sara; Doil, Lisa; Tacey, Kristina; van Luchene, Ryan; Myers, Amanda; Wavrant-De Vrièze, Fabienne; Kaleem, Mona; Hollingworth, Paul; Jehu, Luke; Foy, Catherine; Archer, Nicola; Hamilton, Gillian; Holmans, Peter; Morris, Chris M.; Catanese, Joseph; Sninsky, John; White, Thomas J.; Powell, John; Hardy, John; O’Donovan, Michael; Lovestone, Simon; Jones, Lesley; Morris, John C.; Thal, Leon; Owen, Michael; Williams, Julie; Goate, Alison

    2006-01-01

    Strong evidence of linkage to late-onset Alzheimer disease (LOAD) has been observed on chromosome 10, which implicates a wide region and at least one disease-susceptibility locus. Although significant associations with several biological candidate genes on chromosome 10 have been reported, these findings have not been consistently replicated, and they remain controversial. We performed a chromosome 10–specific association study with 1,412 gene-based single-nucleotide polymorphisms (SNPs), to identify susceptibility genes for developing LOAD. The scan included SNPs in 677 of 1,270 known or predicted genes; each gene contained one or more markers, about half (48%) of which represented putative functional mutations. In general, the initial testing was performed in a white case-control sample from the St. Louis area, with 419 LOAD cases and 377 age-matched controls. Markers that showed significant association in the exploratory analysis were followed up in several other white case-control sample sets to confirm the initial association. Of the 1,397 markers tested in the exploratory sample, 69 reached significance (P<.05). Five of these markers replicated at P<.05 in the validation sample sets. One marker, rs498055, located in a gene homologous to RPS3A (LOC439999), was significantly associated with Alzheimer disease in four of six case-control series, with an allelic P value of .0001 for a meta-analysis of all six samples. One of the case-control samples with significant association to rs498055 was derived from the linkage sample (P=.0165). These results indicate that variants in the RPS3A homologue are associated with LOAD and implicate this gene, adjacent genes, or other functional variants (e.g., noncoding RNAs) in the pathogenesis of this disorder. PMID:16385451

  12. 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

  13. Evidence for a NOD2-independent susceptibility locus for inflammatory bowel disease on chromosome 16p

    PubMed Central

    Hampe, Jochen; Frenzel, Henning; Mirza, Muddassar M.; Croucher, Peter J. P.; Cuthbert, Andrew; Mascheretti, Silvia; Huse, Klaus; Platzer, Matthias; Bridger, Stephen; Meyer, Birgit; Nürnberg, Peter; Stokkers, Pieter; Krawczak, Michael; Mathew, Christopher G.; Curran, Mark; Schreiber, Stefan

    2002-01-01

    Heritable predisposition to inflammatory bowel disease (IBD) has been demonstrated by epidemiological and genetic analysis. Linkage of IBD to broad regions of chromosome 16 has been established by analysis of multiple populations. NOD2, located on proximal 16q, was recently identified as an IBD gene. As the linkage regions on chromosome 16 are large, we have investigated the possibility that NOD2 is not the only IBD gene located on this chromosome. A high-density experiment using 39 microsatellite markers was performed to identify additional regions of association, and to indicate areas of interest for further investigation. A triple-peaked configuration of the linkage curve with peak logarithm of odds (lod) scores of 2.7, 3.2, and 3.1 was observed on proximal 16p, proximal 16q, and central 16q, respectively. The cohort was stratified by coding individuals carrying the NOD2 single nucleotide polymorphism (SNP)8 and SNP13 “unknown.” Significance at the central peak, corresponding to the genomic location of NOD2, then decreased from 3.2 to 1.2. The maximal lod scores on the proximal p-arm (lod = 2.1) and central q-arm (lod = 2.6) changed only moderately. An exploratory association analysis (TRANSMIT) yielded a strong lead at D16S3068 (P = 0.00028). The region around this marker was further investigated by using anonymous SNPs. An associated haplotype containing three SNPs was identified (peak significance P = 0.00027, IBD phenotype). On stratification based on NOD2 genotype, this significance increased to P = 0.0001. These results confirm the importance of NOD2 and provide evidence for a second IBD gene located on chromosome 16p. PMID:11752413

  14. 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.

  15. Chromosome

    MedlinePlus

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

  16. Developmental characterization and chromosomal mapping of the 5-azacytidine-sensitive fluF locus of Aspergillus nidulans.

    PubMed Central

    Tamame, M; Antequera, F; Santos, E

    1988-01-01

    In Aspergillus nidulans, a fungus that possesses negligible, if any, levels of methylation in its genome, low concentrations of 5-azacytidine (5-AC) convert a high percentage of the cell population to fluffy phenotypic variants through a heritable modification of a single nuclear gene (M. Tamame, F. Antequera, J. R. Villanueva, and T. Santos, Mol. Cell. Biol. 3:2287-2297, 1983). This new 5-AC-altered locus, designated here fluF1, was mapped as the closest marker to the centromere that has been identified so far on the right arm of chromosome VIII. Of all mutagens tested, only 5-AC induced the fluffy phenotype with a significant frequency. Furthermore, we determined that the wild-type, dominant allele of the fluF gene was primarily accessible to modification by 5-AC at the initial stages of fungal vegetative growth. These results indicated that 5-AC does not act through random mutagenic action but, rather, that fluF constitutes a specific target for this drug during a well-defined period of fungal development. Alteration of fluF by 5-AC resulted in a dramatic modification of the developmental program of A. nidulans. The resulting fluffy clones were characterized by massive, uncontrolled proliferation of undifferentiated hyphae, a drastic delay in the onset of asexual differentiation (conidiation), and colonies with an invasive nature. These features are reminiscent of the malignant properties of tumor cells. We propose that the locus fluF plays a primary role in the control of cell proliferation in A. nidulans and that its alteration by 5-AC produces pleiotropic modifications of the developmental program of this fungus. Images PMID:2463470

  17. Chromosome

    MedlinePlus

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

  18. 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.

  19. Absence of polymorphism at the ZFY locus on the human Y chromosome.

    PubMed

    Dorit, R L; Akashi, H; Gilbert, W

    1995-05-26

    DNA polymorphism in the Y chromosome, examined at a 729-base pair intron located immediately upstream of the ZFY zinc-finger exon, revealed no sequence variation in a worldwide sample of 38 human males. This finding cannot be explained by global constraint on the intron sequence, because interspecific comparisons with other nonhuman primates revealed phylogenetically informative sequence changes. The invariance likely results from either a recent selective sweep, a recent origin for modern Homo sapiens, recurrent male population bottlenecks, or historically small effective male population sizes. A coalescence model predicts an expected time to a most recent common ancestral male lineage of 270,000 years (95 percent confidence limits: 0 to 800,000 years). PMID:7761836

  20. A locus on chromosome 5 is associated with dilated cardiomyopathy in Doberman Pinschers.

    PubMed

    Mausberg, Theresa-Bernadette; Wess, Gerhard; Simak, Julia; Keller, Lisa; Drögemüller, Michaela; Drögemüller, Cord; Webster, Matthew T; Stephenson, Hannah; Dukes-McEwan, Joanna; Leeb, Tosso

    2011-01-01

    Dilated cardiomyopathy (DCM) is a heterogeneous group of heart diseases with a strong genetic background. Currently, many human DCM cases exist where no causative mutation can be identified. DCM also occurs with high prevalence in several large dog breeds. In the Doberman Pinscher a specific DCM form characterized by arrhythmias and/or echocardiographic changes has been intensively studied by veterinary cardiologists. We performed a genome-wide association study in Doberman Pinschers. Using 71 cases and 70 controls collected in Germany we identified a genome-wide significant association to DCM on chromosome 5. We validated the association in an independent cohort collected in the United Kingdom. There is no known DCM candidate gene under the association signal. Therefore, DCM in Doberman Pinschers offers the chance of identifying a novel DCM gene that might also be relevant for human health. PMID:21625443

  1. A New Essential Hypertension Susceptibility Locus on Chromosome 2p24-p25, Detected by Genomewide Search

    PubMed Central

    Angius, Andrea; Petretto, Enrico; Maestrale, Giovanni Battista; Forabosco, Paola; Casu, Giuseppina; Piras, Daniela; Fanciulli, Manuela; Falchi, Mario; Melis, Paola Maria; Palermo, Mario; Pirastu, Mario

    2002-01-01

    Essential hypertension (EH) is a complex disorder that results from the interaction of a number of susceptibility genes and environmental factors. We studied an isolated Sardinian village (Talana) in which the prevalence of hypertension is comparable to that in most Western populations. Talana exhibits features, such as slow demographic growth, high inbreeding, a low number of founders, stable lifestyle and culture, and accurate genealogical records, that make it suitable for the study of complex disorders. Clinical assessment of the entire adult population (N=∼1,000) identified ∼100 hypertensive subjects. For our study, we selected the individuals with the most-severe EH (i.e., diastolic blood pressure >100 mm Hg), belonging to a single deep-rooted pedigree (12 generations), whose common ancestors lived in the 17th century. We performed a three-stage genomewide search using 36 affected individuals, by means of parametric linkage and allele-sharing approaches. LOD scores >1 were observed on chromosomes 1, 2, 13, 15, 17, and 19 (stage I). The most striking result was found in a 7.57-cM region on chromosome 2p24-p25. All five nonparametric linkage statistics estimated by the SimWalk2 program lie above the significance threshold of P<.008 for the whole region. Similar significance was obtained for 2p24-25 when parametric linkage (LOD score 1.99) and linkage disequilibrium mapping (P=.00006) were used, suggesting that a hypertension-susceptibility locus is located between D2S2278 and D2S168. This finding is strengthened by a recent report of linkage with marker D2S168 in a hypertensive sib-pair sample from China. PMID:12228842

  2. A new autosomal recessive retinitis pigmentosa locus maps on chromosome 2q31-q33.

    PubMed Central

    Bayés, M; Goldaracena, B; Martínez-Mir, A; Iragui-Madoz, M I; Solans, T; Chivelet, P; Bussaglia, E; Ramos-Arroyo, M A; Baiget, M; Vilageliu, L; Balcells, S; Gonzàlez-Duarte, R; Grinberg, D

    1998-01-01

    Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous disease. To date, mutations in four members of the phototransduction cascade have been implicated in ARRP. Additionally, linkage of the disease to three loci on 1p, 1q, and 6p has been described. However, the majority of cases are still uncharacterised. We have performed linkage analysis in a large nuclear ARRP family with five affected sibs. After exclusion of several regions of the genome known to contain loci for retinal dystrophies, a genomic search for linkage to ARRP was undertaken. Positive lod scores were obtained with markers on 2q31-q33 (Zmax at theta = 0.00 of 4.03, 4.12, and 4.12 at D2S364, D2S118, and D2S389, respectively) defining an interval of about 7 cM for this new ARRP locus, between D2S148 and D2S161. Forty-four out of 47 additional ARRP families, tested with markers on 2q32, failed to show linkage, providing evidence of further genetic heterogeneity. Images PMID:9507394

  3. Variant (6;15) translocations in murine plasmacytomas involve a chromosome 15 locus at least 72 kb from the c-myc oncogene.

    PubMed Central

    Cory, S; Graham, M; Webb, E; Corcoran, L; Adams, J M

    1985-01-01

    The variant (6;15) translocations in murine plasmacytomas join the myc oncogene-bearing band of chromosome 15 and the immunoglobulin kappa band of chromosome 6. We recently cloned a region from chromosome 15 linked to C kappa and have now used probes from that region to define the major locus of plasmacytoma variant translocations, which we denote pvt-1. In five of nine plasmacytomas we analysed, the 6;15 translocation resulted from reciprocal recombination between the C kappa locus and a 4.5-kb region of pvt-1. Moreover, nearby we located the region shown by others to have undergone a complex (15;12;6) translocation in plasmacytoma PC7183. All the chromosome 6 breakpoints fell between 1 and 3 kb 5' to C kappa but only two were near J kappa genes. Thus the J kappa -C kappa region appears to be a recombination 'hot spot' in lymphocytes, but the breaks are unlikely to be mediated via V/J recombination enzymes. Comparison of a cloned 108-kb region across pvt-1 and another of 52 kb across c-myc established that the pvt-1 breakpoints lie at least 72 kb from the c-myc promoters. Since c-myc is expressed at a substantial level, the 6;15 translocation apparently activates c-myc. Activation may occur directly, at a remarkable distance along the chromosome, or indirectly, via a putative pvt-1 gene product. Images Fig. 3. Fig. 5. PMID:3924592

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

    PubMed Central

    Quan, Lei; Hutson, Alan; Demant, Peter

    2010-01-01

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

  5. 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.

  6. 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.

  7. 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. PMID:26172745

  8. 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.

  9. 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.

  10. A domestic cat X chromosome linkage map and the sex-linked orange locus: mapping of orange, multiple origins and epistasis over nonagouti.

    PubMed

    Schmidt-Küntzel, Anne; Nelson, George; David, Victor A; Schäffer, Alejandro A; Eizirik, Eduardo; Roelke, Melody E; Kehler, James S; Hannah, Steven S; O'Brien, Stephen J; Menotti-Raymond, Marilyn

    2009-04-01

    A comprehensive genetic linkage map of the domestic cat X chromosome was generated with the goal of localizing the genomic position of the classic X-linked orange (O) locus. Microsatellite markers with an average spacing of 3 Mb were selected from sequence traces of the cat 1.9x whole genome sequence (WGS), including the pseudoautosomal region 1 (PAR1). Extreme variation in recombination rates (centimorgans per megabase) was observed along the X chromosome, ranging from a virtual absence of recombination events in a region estimated to be >30 Mb to recombination frequencies of 15.7 cM/Mb in a segment estimated to be <0.3 Mb. This detailed linkage map was applied to position the X-linked orange gene, placing this locus on the q arm of the X chromosome, as opposed to a previously reported location on the p arm. Fine mapping placed the locus between markers at positions 106 and 116.8 Mb in the current 1.9x-coverage sequence assembly of the cat genome. Haplotype analysis revealed potential recombination events that could reduce the size of the candidate region to 3.5 Mb and suggested multiple origins for the orange phenotype in the domestic cat. Furthermore, epistasis of orange over nonagouti was demonstrated at the genetic level. PMID:19189955

  11. A Domestic cat X Chromosome Linkage Map and the Sex-Linked orange Locus: Mapping of orange, Multiple Origins and Epistasis Over nonagouti

    PubMed Central

    Schmidt-Küntzel, Anne; Nelson, George; David, Victor A.; Schäffer, Alejandro A.; Eizirik, Eduardo; Roelke, Melody E.; Kehler, James S.; Hannah, Steven S.; O'Brien, Stephen J.; Menotti-Raymond, Marilyn

    2009-01-01

    A comprehensive genetic linkage map of the domestic cat X chromosome was generated with the goal of localizing the genomic position of the classic X-linked orange (O) locus. Microsatellite markers with an average spacing of 3 Mb were selected from sequence traces of the cat 1.9× whole genome sequence (WGS), including the pseudoautosomal region 1 (PAR1). Extreme variation in recombination rates (centimorgans per megabase) was observed along the X chromosome, ranging from a virtual absence of recombination events in a region estimated to be >30 Mb to recombination frequencies of 15.7 cM/Mb in a segment estimated to be <0.3 Mb. This detailed linkage map was applied to position the X-linked orange gene, placing this locus on the q arm of the X chromosome, as opposed to a previously reported location on the p arm. Fine mapping placed the locus between markers at positions 106 and 116.8 Mb in the current 1.9×-coverage sequence assembly of the cat genome. Haplotype analysis revealed potential recombination events that could reduce the size of the candidate region to 3.5 Mb and suggested multiple origins for the orange phenotype in the domestic cat. Furthermore, epistasis of orange over nonagouti was demonstrated at the genetic level. PMID:19189955

  12. The cardiovascular implication of single nucleotide polymorphisms of chromosome 9p21 locus among Arab population

    PubMed Central

    El-Menyar, Ayman A.; Rizk, Nasser M.; Al-Qahtani, Awad; AlKindi, Fahad; Elyas, Ahmed; Farag, Fathi; Bakhsh, Fadheela Dad; Ebrahim, Samah; Ahmed, Emad; Al-khinji, Mooza; Al-Thani, Hassan; Suwaidi, Jassim Al

    2015-01-01

    Background: Based on several reports including genome-wide association studies, genetic variability has been linked with higher (nearly half) susceptibility toward coronary artery disease (CAD). We aimed to evaluate the association of chromosome 9p21 single nucleotide polymorphisms (SNPs): rs2383207, rs10757278, and rs10757274 with the risk and severity of CAD among Arab population. Materials and Methods: A prospective observational case-control study was conducted between 2011 and 2012, in which 236 patients with CAD were recruited from the Heart Hospital in Qatar. Patients were categorized according to their coronary angiographic findings. Also, 152 healthy volunteers were studied to determine if SNPs are associated with risk of CAD. All subjects were genotyped for SNPs (rs2383207, rs2383206, rs10757274 and rs10757278) using allele-specific real-time polymerase chain reaction. Results: Patients with CAD had a mean age of 57 ± 10; of them 77% were males, 54% diabetics, and 25% had family history of CAD. All SNPs were in Hardy-Weinberg equilibrium except rs2383206, with call rate >97%. After adjusting for age, sex and body mass index, the carriers of GG genotype for rs2383207 have increased the risk of having CAD with odds ratio (OR) of 1.52 (95% confidence interval [CI] = 1.01-2.961, P = 0.046). Also, rs2383207 contributed to CAD severity with adjusted OR 1.80 (95% CI = 1.04-3.12, P = 0.035) based on the dominant genetic model. The other SNPs (rs10757274 and rs10757278) showed no significant association with the risk of CAD or its severity. Conclusion: Among Arab population in Qatar, only G allele of rs2483207 SNP is significantly associated with risk of CAD and its severity. PMID:26109989

  13. 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

  14. 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

  15. Quantitative genetic study of maximal electroshock seizure threshold in mice: evidence for a major seizure susceptibility locus on distal chromosome 1.

    PubMed

    Ferraro, T N; Golden, G T; Smith, G G; Longman, R L; Snyder, R L; DeMuth, D; Szpilzak, I; Mulholland, N; Eng, E; Lohoff, F W; Buono, R J; Berrettini, W H

    2001-07-01

    We conducted a quantitative trait locus (QTL) mapping study to dissect the multifactorial nature of maximal electroshock seizure threshold (MEST) in C57BL/6 (B6) and DBA/2 (D2) mice. MEST determination involved a standard paradigm in which 8- to 12-week-old mice received one shock per day with a daily incremental increase in electrical current until a maximal seizure (tonic hindlimb extension) was induced. Mean MEST values in parental strains were separated by over five standard deviation units, with D2 mice showing lower values than B6 mice. The distribution of MEST values in B6xD2 F2 intercrossed mice spanned the entire phenotypic range defined by parental strains. Statistical mapping yielded significant evidence for QTLs on chromosomes 1, 2, 5, and 15, which together explained over 60% of the phenotypic variance in the model. The chromosome 1 QTL represents a locus of major effect, accounting for about one-third of the genetic variance. Experiments involving a congenic strain (B6.D2-Mtv7(a)/Ty) enabled more precise mapping of the chromosome 1 QTL and indicate that it lies in the genetic interval between markers D1Mit145 and D1Mit17. These results support the hypothesis that the distal portion of chromosome 1 harbors a gene(s) that has a fundamental role in regulating seizure susceptibility. PMID:11472065

  16. 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

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

    PubMed

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

    2001-01-01

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

  18. 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.

  19. 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

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

    PubMed

    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

    2012-02-15

    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 FEV(1) (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

  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. 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.

  3. 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.

  4. Single nucleotide polymorphisms in an STS region linked to the Ncc-tmp1A locus are informative for characterizing the differentiation of chromosome 1A in wheat.

    PubMed

    Asakura, N; Mori, N; Ishido, T; Ohtsuka, I; Nakamura, C

    2001-10-01

    Homoeoalleles of Ncc confer nucleus-cytoplasm (NC) compatibility on NC hybrids of wheat with the D plasmon of Aegilops squarrosa. To dissect the chromosomal region containing Ncc, a RAPD marker linked to the Ncc-tmplA locus, which is located on chromosome 1A of T timopheevi, was sequenced and converted to a PCR-based sequence-tagged-site (STS) marker. Five single nucleotide polymorphisms (SNPs) between T timopheevi and T turgidum. were detected in a 509-bp genomic DNA fragment. Based on the SNPs, the STS alleles in 164 accessions from emmer wheat, timopheevi wheat and two einkorn wheats, T. urartu and T. boeoticum were surveyed by PCR-RFLP analysis. The sequence comparisons and PCR-RFLP analyses revealed nine alleles based on six SNPs. These SNPs were highly conserved within each group of wheat, and all groups could be distinguished by particular combinations of the SNPs. All accessions of T. urartu had one unique STS allele as compared with the others. Our results indicate that the SNPs in the STS marker linked to the Ncc-tmplA locus would be informative for studies of the differentiation of chromosome 1A in wheat. PMID:11817645

  5. Identification of Stmm3 locus Conferring Resistance to Late-stage Chemically Induced Skin Papillomas on Mouse Chromosome 4 by Congenic Mappingand Allele-specific Alteration Analysis

    PubMed Central

    Saito, Megumi; Okumura, Kazuhiro; Miura, Ikuo; Wakana, Shigeharu; Kominami, Ryo; Wakabayashi, Yuichi

    2014-01-01

    Genome-wide association studies have revealed that many low-penetrance cancer susceptibility loci are located throughout the genome; however, a very limited number of genes have been identified so far. Using a forward genetics approach to map such loci in a mouse skin cancer model, we previously identified strong genetic loci conferring resistance to chemically induced skin papillomas on chromosome 4 and 7 with a large number of [(FVB/N × MSM/Ms) F1 × FVB/N] backcross mice. In this report, we describe a combination of congenic mapping and allele-specific alteration analysis of the loci on chromosome 4. We used linkage analysis and a congenic mouse strain, FVB.MSM-Stmm3 to refine the location of Stmm3 (Skin tumor modifier of MSM 3) locus within a physical interval of about 34 Mb on distal chromosome 4. In addition, we used patterns of allele-specific imbalances in tumors from N2 and N10 congenic mice to narrow down further the region of Stmm3 locus to a physical distance of about 25 Mb. Furthermore, immunohistochemical analysis showed papillomas from congenic mice had less proliferative activity. These results suggest that Stmm3 responsible genes may have an influence on papilloma formation in the two-stage skin carcinogenesis by regulating papilloma growth rather than development. PMID:25077764

  6. Use of a quantitative trait to map a locus associated with severity of positive symptoms in familial schizophrenia to chromosome 6p.

    PubMed Central

    Brzustowicz, L M; Honer, W G; Chow, E W; Hogan, J; Hodgkinson, K; Bassett, A S

    1997-01-01

    A number of recent linkage studies have suggested the presence of a schizophrenia susceptibility locus on chromosome 6p. We evaluated 28 genetic markers, spanning chromosome 6, for linkage to schizophrenia in 10 moderately large Canadian families of Celtic ancestry. Parametric analyses of these families under autosomal dominant and recessive models, using broad and narrow definitions of schizophrenia, produced no significant evidence for linkage. A sib-pair analysis using categorical disease definitions also failed to produce significant evidence for linkage. We then conducted a separate sibpair analysis using scores on positive-symptom (psychotic), negative-symptom (deficit), and general psychopathology-symptom scales as quantitative traits. With the positive symptom-scale scores, the marker D6S1960 produced P = 1.2 x 10(-5) under two-point and P = 5.4 x 10(-6) under multipoint analyses. Using simulation studies, we determined that these nominal P values correspond to empirical P values of .034 and .0085, respectively. These results suggest that a schizophrenia susceptibility locus on chromosome 6p may be related to the severity of psychotic symptoms. Assessment of behavioral quantitative traits may provide increased power over categorical phenotype assignment for detection of linkage in complex psychiatric disorders. PMID:9399881

  7. 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.

  8. 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…

  9. 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

  10. Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa

    SciTech Connect

    Kojis, T.L.; Heinzmann, C.; Ngo, J.T.

    1996-02-01

    In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yielded a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families. 39 refs., 4 figs., 3 tabs.

  11. Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa.

    PubMed Central

    Kojis, T. L.; Heinzmann, C.; Flodman, P.; Ngo, J. T.; Sparkes, R. S.; Spence, M. A.; Bateman, J. B.; Heckenlively, J. R.

    1996-01-01

    In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yielded a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families. PMID:8571961

  12. Confirmation and refinement of an autosomal dominant congenital motor nystagmus locus in chromosome 1q31.3-q32.1.

    PubMed

    Li, Lin; Xiao, Xueshan; Yi, Changxian; Jiao, Xiaodong; Guo, Xiangming; Hejtmancik, James Fielding; Zhang, Qingjiong

    2012-12-01

    Congenital motor nystagmus (CMN) is characterized by early-onset bilateral ocular oscillations. To identify the disease locus for autosomal dominant CMN in a Chinese family 86001, clinical data, including slit lamp and funduscopic examination and blood samples were collected from family. Genomic DNA was prepared from leukocytes, and a genome-wide linkage scan was performed using 382 polymorphic microsatellite markers and two-point linkage analysis using the logarithm of odds (LOD) score method as implemented in the LINKAGE program package. Maximum two-point scores were calculated using ILINK, and LINKMAP was used for multipoint analysis. All nine affected individuals in the family showed typical phenotypes for CMN. Maximum two-point LOD scores (3.61 at θ=0) were obtained with D1S2619, D1S2877 and D1S2622.The 24.6 cM (28.07 Mb) linked region is flanked by markers D1S218 and D1S2655, placing the disease locus on chromosome 1q25.2-1q32.1. Multipoint analysis confirmed linkage to the region of D1S218 and D1S2655 with Maximum two-point scores of 3.61. The linkage interval overlaps with that of a newly reported CMN locus on 1q31-q32.2 and narrows down the linked region to 5.90 cM (5.92 Mb). This study confirms and refines a novel locus for autosomal dominant CMN to chromosome 1q31.3-q32.1 (5.90 cM) and demonstrates its presence in the Chinese population. PMID:22914672

  13. 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

  14. A locus for Waardenburg syndrome type II maps to chromosome 1p13.3-2.1

    SciTech Connect

    Lalwani, A.K.; San Agustin, T.B.; Wilcox, E.R.

    1994-09-01

    Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes and distinctive facial features. WS type I (WS1) is characterized by a high frequency of dystopia canthorum whereas WS type II (WS2) individuals have normal inter canthal distances. Previous studies have shown that WS1 is caused by mutations in the PAX3 gene on chromosome 2q whereas WS2 is unlinked to PAX3. However, analyses of WS2 families have been complicated by the possibility of misdiagnosis of secondary cases with mild features of WS2. We initiated a genome search in 8 WS2 families. Suggestive evidence for linkage to D1S248 and AMY2B was found in one family (both markers: Z-max=2.4 at {Theta}=0), to D1S485 and D1S495 in a second family (both markers: Z-max=2.2 at {Theta}=0), and to D1S248 in a third family (Z-max=1.1 at {Theta}=.11). WS2 was not linked to any of these markers in the total group of families. Location scores for each family were calculated by a six-locus analysis using the marker map AMY2B/D1S486 - .03 - D1S495 - .02 - D1S248 - .05 - D1S457 - .04 - D1S250. Assessment of these scores for linkage and heterogeneity using the admixture test revealed significant evidence for linkage (P<.0001) under the assumption of heterogeneity ({alpha}=.40). The most likely location for WS2 is at D1S495, although either of the intervals flanking this marker may contain the mutant gene. All other locations were ruled out with odds of greater than l00 to 1. Our findings suggest that there are at least two loci for WS type II. Complementary crossovers in the linked families make feasible attempts to narrow the location of the WS2 gene by positional cloning. Analyses of additional families will be needed to estimate more precisely the proportion of linked families and identify the gene.

  15. Cloning of cDNA encoding human rapsyn and mapping of the RAPSN gene locus to chromosome 11p11.2-p11.1

    SciTech Connect

    Buckel, A.; Beeson, D.; Vincent, A.

    1996-08-01

    We have isolated and sequenced cDNA clones for the human 43-kDa acetylcholine receptor-associated protein rapsyn. The cDNA encodes a 412-amino-acid protein that has a predicted molecular mass of 46,330 Da and shows 96% sequence identity with mouse rapsyn. Analysis of PCR amplifications, first from somatic cell hybrids and subsequently from radiation hybrids, localizes the human RAPSN gene locus to chromosome 11p11.2-p11.1 in close proximity to ACP2. 12 refs., 2 figs.

  16. A Mouse Homeo Box Gene, Hox-1.5, and the Morphological Locus, Hd, Map to within 1 Cm on Chromosome 6

    PubMed Central

    Mock, Beverly A.; D'Hoostelaere, Lawrence A.; Matthai, Roberta; Huppi, Konrad

    1987-01-01

    Mo-10, a homeo box-containing sequence in the Hox-1 complex of genes referred to as Hox-1.5, was found to be polymorphic in inbred and wild mice, and a strain distribution of three allelic forms of Hox-1.5 are reported. The position of Hox-1.5 was mapped in backcross experiments to within 1 cM of the hypodactyly locus on chromosome 6. This identifies the Hd mutation as a useful model for the examination of homeo box expression during mammalian development. PMID:2887485

  17. 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

  18. 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.

  19. 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.

  20. 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. PMID:25349420

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

    PubMed Central

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

    2014-01-01

    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. PMID:25349420

  2. A 1.6-Mb contig of yeast artificial chromosomes around the human factor VIII gene reveals three regions homologous to probes for the DXS115 locus and two for the DXYS64 locus.

    PubMed Central

    Freije, D; Schlessinger, D

    1992-01-01

    Two yeast artificial chromosome (YAC) libraries were screened for probes in Xq28, around the gene for coagulation factor VIII (F8). A set of 30 YACs were recovered and assembled into a contig spanning at least 1.6 Mb from the DXYS64 locus to the glucose 6-phosphate dehydrogenase gene (G6PD). Overlaps among the YACs were determined by several fingerprinting techniques and by additional probes generated from YAC inserts by using Alu-vector or ligation-mediated PCR. Analysis of more than 30 probes and sequence-tagged sites (STSs) made from the region revealed the presence of several homologous genomic segments. For example, a probe for the DXYS64 locus, which maps less than 500 kb 5' of F8, detects a similar but not identical locus between F8 and G6PD. Also, a probe for the DXS115 locus detects at least three identical copies in this region, one in intron 22 of F8 and at least two more, which are upstream of the 5' end of the gene. Comparisons of genomic and YAC DNA suggest that the multiple loci are not created artifactually during cloning but reflect the structure of uncloned human DNA. On the basis of these data, the most likely order for the loci analyzed is tel-DXYS61-DXYS64-(DXS115-3-DXS115-2)-5'F8-(D XS115-1)-3'F8-G6PD. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1609806

  3. A triallelic genetic male sterility locus in Brassica napus: an integrative strategy for its physical mapping and possible local chromosome evolution around it

    PubMed Central

    Lu, Wei; Liu, Jun; Xin, Qiang; Wan, Lili; Hong, Dengfeng; Yang, Guangsheng

    2013-01-01

    Background and Aims Spontaneous male sterility is an advantageous trait for both constructing efficient pollination control systems and for understanding the developmental process of the male reproductive unit in many crops. A triallelic genetic male-sterile locus (BnMs5) has been identified in Brassica napus; however, its complicated genome structure has greatly hampered the isolation of this locus. The aim of this study was to physically map BnMs5 through an integrated map-based cloning strategy and analyse the local chromosomal evolution around BnMs5. Methods A large F2 population was used to integrate the existing genetic maps around BnMs5. A map-based cloning strategy in combination with comparative mapping among B. napus, Arabidopsis, Brassica rapa and Brassica oleracea was employed to facilitate the identification of a target bacterial artificial chromosome (BAC) clone covering the BnMs5 locus. The genomic sequences from the Brassica species were analysed to reveal the regional chromosomal evolution around BnMs5. Key Results BnMs5 was finally delimited to a 0·3-cM genetic fragment from an integrated local genetic map, and was anchored on the B. napus A8 chromosome. Screening of a B. napus BAC clone library and identification of the positive clones validated that JBnB034L06 was the target BAC clone. The closest flanking markers restrict BnMs5 to a 21-kb region on JBnB034L06 containing six predicted functional genes. Good collinearity relationship around BnMs5 between several Brassica species was observed, while violent chromosomal evolutionary events including insertions/deletions, duplications and single nucleotide mutations were also found to have extensively occurred during their divergence. Conclusions This work represents major progress towards the molecular cloning of BnMs5, as well as presenting a powerful, integrative method to mapping loci in plants with complex genomic architecture, such as the amphidiploid B. napus. PMID:23243189

  4. Genomewide Search for Type 2 Diabetes–Susceptibility Genes in French Whites: Evidence for a Novel Susceptibility Locus for Early-Onset Diabetes on Chromosome 3q27-qter and Independent Replication of a Type 2–Diabetes Locus on Chromosome 1q21–q24

    PubMed Central

    Vionnet, Nathalie; Hani, El Habib; Dupont, Sophie; Gallina, Sophie; Francke, Stephan; Dotte, Sébastien; De Matos, Frédérique; Durand, Emmanuelle; Leprêtre, Frédéric; Lecoeur, Cécile; Gallina, Philippe; Zekiri, Lirije; Dina, Christian; Froguel, Philippe

    2000-01-01

    Despite recent advances in the molecular genetics of type 2 diabetes, the majority of susceptibility genes in humans remain to be identified. We therefore conducted a 10-cM genomewide search (401 microsatellite markers) for type 2 diabetes–related traits in 637 members of 143 French pedigrees ascertained through multiple diabetic siblings, to map such genes in the white population. Nonparametric two-point and multipoint linkage analyzes—using the MAPMAKER-SIBS (MLS) and MAXIMUM-BINOMIAL-LIKELIHOOD (MLB) programs for autosomal markers and the ASPEX program for chromosome X markers—were performed with six diabetic phenotypes: diabetes and diabetes or glucose intolerance (GI), as well as with each of the two phenotypes associated with normal body weight (body-mass index<27 kg/m2) or early age at diagnosis (<45 years). In a second step, high-resolution genetic mapping (∼2 cM) was performed in regions on chromosomes 1 and 3 loci showing the strongest linkage to diabetic traits. We found evidence for linkage with diabetes or GI diagnosed at age <45 years in 92 affected sib pairs from 55 families at the D3S1580 locus on chromosome 3q27-qter using MAPMAKER-SIBS (MLS = 4.67, P=.000004), supported by the MLB statistic (MLB-LOD=3.43, P=.00003). We also found suggestive linkage between the lean diabetic status and markers APOA2–D1S484 (MLS = 3.04, P=.00018; MLB-LOD=2.99, P=.00010) on chromosome 1q21-q24. Several other chromosomal regions showed indication of linkage with diabetic traits, including markers on chromosome 2p21-p16, 10q26, 20p, and 20q. These results (a) showed evidence for a novel susceptibility locus for type 2 diabetes in French whites on chromosome 3q27-qter and (b) confirmed the previously reported diabetes-susceptibility locus on chromosome 1q21-q24. Saturation on both chromosomes narrowed the regions of interest down to an interval of <7 cM. PMID:11067779

  5. A genome scan in multigenerational families with dyslexia: Identification of a novel locus on chromosome 2q that contributes to phonological decoding efficiency.

    PubMed

    Raskind, W H; Igo, R P; Chapman, N H; Berninger, V W; Thomson, J B; Matsushita, M; Brkanac, Z; Holzman, T; Brown, M; Wijsman, E M

    2005-07-01

    Dyslexia is a common and complex developmental disorder manifested by unexpected difficulty in learning to read. Multiple different measures are used for diagnosis, and may reflect different biological pathways related to the disorder. Impaired phonological decoding (translation of written words without meaning cues into spoken words) is thought to be a core deficit. We present a genome scan of two continuous measures of phonological decoding ability: phonemic decoding efficiency (PDE) and word attack (WA). PDE measures both accuracy and speed of phonological decoding, whereas WA measures accuracy alone. Multipoint variance component linkage analyses (VC) and Markov chain Monte-Carlo (MCMC) multipoint joint linkage and segregation analyses were performed on 108 families. A strong signal was observed on chromosome 2 for PDE using both VC (LOD=2.65) and MCMC methods (intensity ratio (IR)=32.1). The IR is an estimate of the ratio of the posterior to prior probability of linkage in MCMC analysis. The chromosome 2 signal was not seen for WA. More detailed mapping with additional markers provided statistically significant evidence for linkage of PDE to chromosome 2, with VC-LOD=3.0 and IR=59.6 at D2S1399. Parametric analyses of PDE, using a model obtained by complex segregation analysis, provided a multipoint maximum LOD=2.89. The consistency of results from three analytic approaches provides strong evidence for a locus on chromosome 2 that influences speed but not accuracy of phonological decoding. PMID:15753956

  6. Susceptibility to anthrax lethal toxin-induced rat death is controlled by a single chromosome 10 locus that includes rNlrp1.

    PubMed

    Newman, Zachary L; Printz, Morton P; Liu, Shihui; Crown, Devorah; Breen, Laura; Miller-Randolph, Sharmina; Flodman, Pamela; Leppla, Stephen H; Moayeri, Mahtab

    2010-05-01

    Anthrax lethal toxin (LT) is a bipartite protease-containing toxin and a key virulence determinant of Bacillus anthracis. In mice, LT causes the rapid lysis of macrophages isolated from certain inbred strains, but the correlation between murine macrophage sensitivity and mouse strain susceptibility to toxin challenge is poor. In rats, LT induces a rapid death in as little as 37 minutes through unknown mechanisms. We used a recombinant inbred (RI) rat panel of 19 strains generated from LT-sensitive and LT-resistant progenitors to map LT sensitivity in rats to a locus on chromosome 10 that includes the inflammasome NOD-like receptor (NLR) sensor, Nlrp1. This gene is the closest rat homolog of mouse Nlrp1b, which was previously shown to control murine macrophage sensitivity to LT. An absolute correlation between in vitro macrophage sensitivity to LT-induced lysis and animal susceptibility to the toxin was found for the 19 RI strains and 12 additional rat strains. Sequencing Nlrp1 from these strains identified five polymorphic alleles. Polymorphisms within the N-terminal 100 amino acids of the Nlrp1 protein were perfectly correlated with LT sensitivity. These data suggest that toxin-mediated lethality in rats as well as macrophage sensitivity in this animal model are controlled by a single locus on chromosome 10 that is likely to be the inflammasome NLR sensor, Nlrp1. PMID:20502689

  7. 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.

  8. Susceptibility to insulin-dependent diabetes mellitus maps to a locus (IDDM11) on human chromosome 14q24.3-q31

    SciTech Connect

    Field, L.L.; Tobias, R.; Thomson, G.

    1996-04-01

    To locate genes predisposing to insulin-dependent diabetes mellitus (IDDM), an autoimmune disorder resulting from destruction of the insulin-producing pancreatic cells, we are testing linkage of IDDM susceptibility to polymorphic markers across the genome using families with two or more IDDM children. A new susceptibility locus (IDDM11) has been localized to chromosome 14q24.3-q31 by detection of significant linkage to microsatellite D14S67, using both maximum likelihood methods D14S67, using both maximum likelihood methods (LOD{sub max} = 4.0 at {theta} = 0.20) and affected sib pair (ASP) methods (P = 1 x 10{sup -5}). This represents the strongest reported evidence for linkage to any IDDM locus outside the HLA region. The subset of families in which affected children did not show increased sharing of HLA genes (HLA sharing {le}50%) provided most of the support for D14S67 linkage (LOD{sub max}4.6 at {theta} = 0.12;ASP P < 5 x 10{sup -6}). There was significant linkage heterogeneity between the HLA-defined subsets of families (P = 0.009), suggesting that IDDM11 may be an important susceptibility locus in families lacking strong HLA region predisposition. 52 refs., 2 figs., 3 tabs.

  9. 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.

  10. High resolution SNP array genomic profiling of peripheral T cell lymphomas, not otherwise specified, identifies a subgroup with chromosomal aberrations affecting the REL locus.

    PubMed

    Hartmann, Sylvia; Gesk, Stefan; Scholtysik, René; Kreuz, Markus; Bug, Stefanie; Vater, Inga; Döring, Claudia; Cogliatti, Sergio; Parrens, Marie; Merlio, Jean-Philippe; Kwiecinska, Anna; Porwit, Anna; Piccaluga, Pier Paolo; Pileri, Stefano; Hoefler, Gerald; Küppers, Ralf; Siebert, Reiner; Hansmann, Martin-Leo

    2010-02-01

    Little is known about genomic aberrations in peripheral T cell lymphoma, not otherwise specified (PTCL NOS). We studied 47 PTCL NOS by 250k GeneChip single nucleotide polymorphism arrays and detected genomic imbalances in 22 of the cases. Recurrent gains and losses were identified, including gains of chromosome regions 1q32-43, 2p15-16, 7, 8q24, 11q14-25, 17q11-21 and 21q11-21 (> or = 5 cases each) as well as losses of chromosome regions 1p35-36, 5q33, 6p22, 6q16, 6q21-22, 8p21-23, 9p21, 10p11-12, 10q11-22, 10q25-26, 13q14, 15q24, 16q22, 16q24, 17p11, 17p13 and Xp22 (> or = 4 cases each). Genomic imbalances affected several regions containing members of nuclear factor-kappaB signalling and genes involved in cell cycle control. Gains of 2p15-16 were confirmed in each of three cases analysed by fluorescence in situ hybridization (FISH) and were associated with breakpoints at the REL locus in two of these cases. Three additional cases with gains of the REL locus were detected by FISH among 18 further PTCL NOS. Five of 27 PTCL NOS investigated showed nuclear expression of the REL protein by immunohistochemistry, partly associated with genomic gains of the REL locus. Therefore, in a subgroup of PTCL NOS gains/rearrangements of REL and expression of REL protein may be of pathogenetic relevance. PMID:19863542

  11. 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.

  12. Quantitative Trait Locus Mapping of Increased Fusarium Head Blight Susceptibility Associated with a Wild Emmer Wheat Chromosome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chromosome 2A of wild emmer (Triticum turgidum var. dicoccoides) line Israel A increases Fusarium head blight (FHB) severity when present in durum wheat (T. turgidum var. durum) cvc. Langdon (LDN), suggesting that FHB susceptibility genes are located on this chromosome. The goals of this study were ...

  13. 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.

  14. Increased support for linkage of a novel locus on chromosome 5q13 for essential hypertension in the British Genetics of Hypertension Study.

    PubMed

    Munroe, Patricia B; Wallace, Chris; Xue, Ming-Zhan; Marçano, Ana Carolina B; Dobson, Richard J; Onipinla, Abiodun K; Burke, Beverley; Gungadoo, Johannie; Newhouse, Stephen J; Pembroke, Janine; Brown, Morris; Dominiczak, Anna F; Samani, Nilesh J; Lathrop, Mark; Connell, John; Webster, John; Clayton, David; Farrall, Martin; Mein, Charles A; Caulfield, Mark

    2006-07-01

    Human hypertension arises from a combination of genetic factors and lifestyle influences. With cardiovascular disease set to become the number 1 cause of death worldwide, it is important to understand the etiologic mechanisms for hypertension, because these might provide new routes to improved treatment. The British Genetics of Hypertension Study has recently published a primary genome screen that identified 4 chromosomal regions of interest. We have now genotyped additional markers to confirm the most promising regions for follow-up studies. Thirty-four additional microsatellites were genotyped in our severely hypertensive affected sibling pair resource (now 1635 families with 2142 affected sibling pairs), leading to a substantial increase in information content in the regions of interest. We found increased support for linkage of chromosome 5q13 to human hypertension (multipoint logarithm of odds=2.50) with 3 adjacent markers yielding single point logarithm of odds scores of 3.22, 2.84, and 2.51. The placement of additional markers on 2q, 6q, and 9q diminished support for linkage in these regions. However, the addition of new data and families identified novel regions of interest on chromosomes 1q and 11q. The 3 positive markers in the chromosome 5 region were also genotyped in 712 distinct parent-offspring trios with the same severe phenotype to replicate linkage and association. Borderline support for replication was found (P=0.07). We found increased evidence for linkage and borderline-significant evidence for association for a hypertension susceptibility locus on chromosome 5q13 that is worthy of detailed fine mapping and assessment of candidate genes. PMID:16754790

  15. Chromosome-Specific Single-Locus FISH Probes Allow Anchorage of an 1800-Marker Integrated Radiation-Hybrid/Linkage Map of the Domestic Dog Genome to All Chromosomes

    PubMed Central

    Breen, Matthew; Jouquand, Sophie; Renier, Corinne; Mellersh, Cathryn S.; Hitte, Christophe; Holmes, Nigel G.; Chéron, Angélique; Suter, Nicola; Vignaux, Françoise; Bristow, Anna E.; Priat, Catherine; McCann, E.; André, Catherine; Boundy, Sam; Gitsham, Paul; Thomas, Rachael; Bridge, Wendy L.; Spriggs, Helen F.; Ryder, Ed J.; Curson, Alistair; Sampson, Jeff; Ostrander, Elaine A.; Binns, Matthew M.; Galibert, Francis

    2001-01-01

    We present here the first fully integrated, comprehensive map of the canine genome, incorporating detailed cytogenetic, radiation hybrid (RH), and meiotic information. We have mapped a collection of 266 chromosome-specific cosmid clones, each containing a microsatellite marker, to all 38 canine autosomes by fluorescence in situ hybridization (FISH). A 1500-marker RH map, comprising 1078 microsatellites, 320 dog gene markers, and 102 chromosome-specific markers, has been constructed using the RHDF5000-2 whole-genome radiation hybrid panel. Meiotic linkage analysis was performed, with at least one microsatellite marker from each dog autosome on a panel of reference families, allowing one meiotic linkage group to be anchored to all 38 dog autosomes. We present a karyotype in which each chromosome is identified by one meiotic linkage group and one or more RH groups. This updated integrated map, containing a total of 1800 markers, covers >90% of the dog genome. Positional selection of anchor clones enabled us, for the first time, to orientate nearly all of the integrated groups on each chromosome and to evaluate the extent of individual chromosome coverage in the integrated genome map. Finally, the inclusion of 320 dog genes into this integrated map enhances existing comparative mapping data between human and dog, and the 1000 mapped microsatellite markers constitute an invaluable tool with which to perform genome scanning studies on pedigrees of interest. PMID:11591656

  16. A high-resolution annotated physical map of the human chromosome 13q12-13 region containing the breast cancer susceptibility locus BRCA2.

    PubMed Central

    Fischer, S G; Cayanis, E; de Fatima Bonaldo, M; Bowcock, A M; Deaven, L L; Edelman, I S; Gallardo, T; Kalachikov, S; Lawton, L; Longmire, J L; Lovett, M; Osborne-Lawrence, S; Rothstein, R; Russo, J J; Soares, M B; Sunjevaric, I; Venkatraj, V S; Warburton, D; Zhang, P; Efstratiadis, A

    1996-01-01

    Various types of physical mapping data were assembled by developing a set of computer programs (Integrated Mapping Package) to derive a detailed, annotated map of a 4-Mb region of human chromosome 13 that includes the BRCA2 locus. The final assembly consists of a yeast artificial chromosome (YAC) contig with 42 members spanning the 13q12-13 region and aligned contigs of 399 cosmids established by cross-hybridization between the cosmids, which were selected from a chromosome 13-specific cosmid library using inter-Alu PCR probes from the YACs. The end sequences of 60 cosmids spaced nearly evenly across the map were used to generate sequence-tagged sites (STSs), which were mapped to the YACs by PCR. A contig framework was generated by STS content mapping, and the map was assembled on this scaffold. Additional annotation was provided by 72 expressed sequences and 10 genetic markers that were positioned on the map by hybridization to cosmids. Images Fig. 3 PMID:8570617

  17. 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.

  18. Insights into the preservation of the homomorphic sex-determining chromosome of Aedes aegypti from the discovery of a male-biased gene tightly linked to the M-locus.

    PubMed

    Hall, Andrew Brantley; Timoshevskiy, Vladimir A; Sharakhova, Maria V; Jiang, Xiaofang; Basu, Sanjay; Anderson, Michelle A E; Hu, Wanqi; Sharakhov, Igor V; Adelman, Zach N; Tu, Zhijian

    2014-01-01

    The preservation of a homomorphic sex-determining chromosome in some organisms without transformation into a heteromorphic sex chromosome is a long-standing enigma in evolutionary biology. A dominant sex-determining locus (or M-locus) in an undifferentiated homomorphic chromosome confers the male phenotype in the yellow fever mosquito Aedes aegypti. Genetic evidence suggests that the M-locus is in a nonrecombining region. However, the molecular nature of the M-locus has not been characterized. Using a recently developed approach based on Illumina sequencing of male and female genomic DNA, we identified a novel gene, myo-sex, that is present almost exclusively in the male genome but can sporadically be found in the female genome due to recombination. For simplicity, we define sequences that are primarily found in the male genome as male-biased. Fluorescence in situ hybridization (FISH) on A. aegypti chromosomes demonstrated that the myo-sex probe localized to region 1q21, the established location of the M-locus. Myo-sex is a duplicated myosin heavy chain gene that is highly expressed in the pupa and adult male. Myo-sex shares 83% nucleotide identity and 97% amino acid identity with its closest autosomal paralog, consistent with ancient duplication followed by strong purifying selection. Compared with males, myo-sex is expressed at very low levels in the females that acquired it, indicating that myo-sex may be sexually antagonistic. This study establishes a framework to discover male-biased sequences within a homomorphic sex-determining chromosome and offers new insights into the evolutionary forces that have impeded the expansion of the nonrecombining M-locus in A. aegypti. PMID:24398378

  19. Insights into the Preservation of the Homomorphic Sex-Determining Chromosome of Aedes aegypti from the Discovery of a Male-Biased Gene Tightly Linked to the M-Locus

    PubMed Central

    Hall, Andrew Brantley; Timoshevskiy, Vladimir A.; Sharakhova, Maria V.; Jiang, Xiaofang; Basu, Sanjay; Anderson, Michelle A.E.; Hu, Wanqi; Sharakhov, Igor V.; Adelman, Zach N.; Tu, Zhijian

    2014-01-01

    The preservation of a homomorphic sex-determining chromosome in some organisms without transformation into a heteromorphic sex chromosome is a long-standing enigma in evolutionary biology. A dominant sex-determining locus (or M-locus) in an undifferentiated homomorphic chromosome confers the male phenotype in the yellow fever mosquito Aedes aegypti. Genetic evidence suggests that the M-locus is in a nonrecombining region. However, the molecular nature of the M-locus has not been characterized. Using a recently developed approach based on Illumina sequencing of male and female genomic DNA, we identified a novel gene, myo-sex, that is present almost exclusively in the male genome but can sporadically be found in the female genome due to recombination. For simplicity, we define sequences that are primarily found in the male genome as male-biased. Fluorescence in situ hybridization (FISH) on A. aegypti chromosomes demonstrated that the myo-sex probe localized to region 1q21, the established location of the M-locus. Myo-sex is a duplicated myosin heavy chain gene that is highly expressed in the pupa and adult male. Myo-sex shares 83% nucleotide identity and 97% amino acid identity with its closest autosomal paralog, consistent with ancient duplication followed by strong purifying selection. Compared with males, myo-sex is expressed at very low levels in the females that acquired it, indicating that myo-sex may be sexually antagonistic. This study establishes a framework to discover male-biased sequences within a homomorphic sex-determining chromosome and offers new insights into the evolutionary forces that have impeded the expansion of the nonrecombining M-locus in A. aegypti. PMID:24398378

  20. 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

  1. 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

  2. Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

    PubMed Central

    Evangelou, Evangelos; Valdes, Ana M.; Kerkhof, Hanneke J.M; Styrkarsdottir, Unnur; Zhu, YanYan; Meulenbelt, Ingrid; Lories, Rik J.; Karassa, Fotini B.; Tylzanowski, Przemko; Bos, Steffan D.; Akune, Toru; Arden, Nigel K.; Carr, Andrew; Chapman, Kay; Cupples, L. Adrienne; Dai, Jin; Deloukas, Panos; Doherty, Michael; Doherty, Sally; Engstrom, Gunnar; Gonzalez, Antonio; Halldorsson, Bjarni V.; Hammond, Christina L.; Hart, Deborah J.; Helgadottir, Hafdis; Hofman, Albert; Ikegawa, Shiro; Ingvarsson, Thorvaldur; Jiang, Qing; Jonsson, Helgi; Kaprio, Jaakko; Kawaguchi, Hiroshi; Kisand, Kalle; Kloppenburg, Margreet; Kujala, Urho M.; Lohmander, L. Stefan; Loughlin, John; Luyten, Frank P.; Mabuchi, Akihiko; McCaskie, Andrew; Nakajima, Masahiro; Nilsson, Peter M.; Nishida, Nao; Ollier, William E.R.; Panoutsopoulou, Kalliope; van de Putte, Tom; Ralston, Stuart H.; Rivadeneira, Fernado; Saarela, Janna; Schulte-Merker, Stefan; Slagboom, P. Eline; Sudo, Akihiro; Tamm, Agu; Tamm, Ann; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tsezou, Aspasia; Wallis, Gillian A.; Wilkinson, J. Mark; Yoshimura, Noriko; Zeggini, Eleftheria; Zhai, Guangju; Zhang, Feng; Jonsdottir, Ingileif; Uitterlinden, Andre G.; Felson, David T; van Meurs, Joyce B.; Stefansson, Kari; Ioannidis, John P.A.; Spector, Timothy D.

    2013-01-01

    Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in the elderly. It is characterized by changes in joint structure including degeneration of the articular cartilage and its etiology is multifactorial with a strong postulated genetic component. We performed a meta-analysis of four genome-wide association (GWA) studies of 2,371 knee OA cases and 35,909 controls in Caucasian populations. Replication of the top hits was attempted with data from additional ten replication datasets. With a cumulative sample size of 6,709 cases and 44,439 controls, we identified one genome-wide significant locus on chromosome 7q22 for knee OA (rs4730250, p-value=9.2×10−9), thereby confirming its role as a susceptibility locus for OA. The associated signal is located within a large (500kb) linkage disequilibrium (LD) block that contains six genes; PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like), and BCAP29 (the B-cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment. PMID:21068099

  3. 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.

  4. 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

  5. Concurrent copy number variations on chromosome 8 and 22 combined with mutation at FGA locus revealed in a parentage testing case.

    PubMed

    Yang, Yaran; Ren, He; Chen, Wei; Xie, Bingbing; Wang, Yan; Shi, Yan; Chen, Chong; Li, Chen; Yi, Le; Fang, Xiangdong; Yan, Jiangwei

    2015-11-01

    Copy number variations (CNVs) are one of the major sources of human genetic diversity and are associated with rare genomic disorders as well as complex traits and diseases. A copy number variation was observed at the D8S1179 locus during routine STR based parentage testing, in which the child exhibited three alleles, "13, 15, 16", with the putative father a homozygous "15" and the mother homozygous "13". In addition, in the same testing case, there was a one-step mutation at the STR locus FGA, in which the putative father was a "22, 24", the mother was a "22, 25", and the child was a "22, 23". After further investigations by re-amplified with different primer sets, clone-based sequencing, karyotype analysis and whole-genome SNP analysis, the results showed that the child had the CNVs at chromosome 8q24.3 and 22q11.21. In conclusion, for parentage testing cases encountered with tri-allele patterns, more testings, such as cloning sequencing, karyotyping, or even whole genome analysis, as well as more appropriate statistical estimations might be conducted to further confirm or exclude the relationship. PMID:26186693

  6. 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

  7. 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

  8. Genomic analysis of the Snn1 locus on wheat chromosome arm 1BS and the identification of candidate genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pathogen Stagonospora nodorum produces multiple host-selective toxins (HSTs) that induce cell death and necrosis in sensitive wheat genotypes. One such HST is SnTox1, which interacts with the host gene Snn1 on wheat chromosome arm 1BS to cause necrosis leading to disease susceptibility. Toward t...

  9. 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

  10. High-resolution meiotic and physical mapping of the best vitelliform macular dystrophy (VMD2) locus to pericentromeric chromosome 11.

    PubMed Central

    Weber, B. H.; Vogt, G.; Stöhr, H.; Sander, S.; Walker, D.; Jones, C.

    1994-01-01

    Best vitelliform macular dystrophy (VMD2) has previously been linked to several microsatellite markers from chromosome 11. Subsequently, additional genetic studies have refined the Best disease region to a 3.7-cM interval flanked by markers at D11S903 and PYGM. To further narrow the interval containing the Best disease gene 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 disease chromosomes. We identified six markers from within the D11S903-PYGM interval that show no recombination with the defective gene in three multigeneration Best 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 on the short arm and at D11S480 in band q13.2-13.3 on the proximal long arm. This study demonstrates that the physical size of the Best disease region is exceedingly larger than previously estimated from the genetic data, because of the proximity of the defective gene to the centromere of chromosome 11. Images Figure 2 PMID:7977378

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

    SciTech Connect

    Weber, B.H.F.; Vogt, G.; Stoehr, H.; Sander, S.; Walker, D.; Jones, C.

    1994-12-01

    Best vitelliform macular dystrophy (VMD2) has previously been linked to several microsatellite markers from chromosome 11. Subsequently, additional genetic studies have refined the Best disease region to a 3.7-cM interval flanked by markers at D11S903 and PYGM. To further narrow the interval containing the Best disease gene 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 disease chromosomes. We identified six markers from within the D11S903-PYGM interval that show no recombination with the defective gene in three multigeneration Best 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 on the short arm and at D11S480 in band q13.2-13.3 on the proximal long arm. This study demonstrates that the physical size of the Best disease region is exceedingly larger than previously estimated from the genetic data, because of the proximity of the defective gene to the centromere of chromosome 11.

  12. High-resolution meiotic and physical mapping of the best vitelliform macular dystrophy (VMD2) locus to pericentromeric chromosome 11.

    PubMed

    Weber, B H; Vogt, G; Stöhr, H; Sander, S; Walker, D; Jones, C

    1994-12-01

    Best vitelliform macular dystrophy (VMD2) has previously been linked to several microsatellite markers from chromosome 11. Subsequently, additional genetic studies have refined the Best disease region to a 3.7-cM interval flanked by markers at D11S903 and PYGM. To further narrow the interval containing the Best disease gene 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 disease chromosomes. We identified six markers from within the D11S903-PYGM interval that show no recombination with the defective gene in three multigeneration Best 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 on the short arm and at D11S480 in band q13.2-13.3 on the proximal long arm. This study demonstrates that the physical size of the Best disease region is exceedingly larger than previously estimated from the genetic data, because of the proximity of the defective gene to the centromere of chromosome 11. PMID:7977378

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. The ripX Locus of Bacillus subtilis Encodes a Site-Specific Recombinase Involved in Proper Chromosome Partitioning

    PubMed Central

    Sciochetti, Stephen A.; Piggot, Patrick J.; Sherratt, David J.; Blakely, Garry

    1999-01-01

    The Bacillus subtilis ripX gene encodes a protein that has 37 and 44% identity with the XerC and XerD site-specific recombinases of Escherichia coli. XerC and XerD are hypothesized to act in concert at the dif site to resolve dimeric chromosomes formed by recombination during replication. Cultures of ripX mutants contained a subpopulation of unequal-size cells held together in long chains. The chains included anucleate cells and cells with aberrantly dense or diffuse nucleoids, indicating a chromosome partitioning failure. This result is consistent with RipX having a role in the resolution of chromosome dimers in B. subtilis. Spores contain a single uninitiated chromosome, and analysis of germinated, outgrowing spores showed that the placement of FtsZ rings and septa is affected in ripX strains by the first division after the initiation of germination. The introduction of a recA mutation into ripX strains resulted in only slight modifications of the ripX phenotype, suggesting that chromosome dimers can form in a RecA-independent manner in B. subtilis. In addition to RipX, the CodV protein of B. subtilis shows extensive similarity to XerC and XerD. The RipX and CodV proteins were shown to bind in vitro to DNA containing the E. coli dif site. Together they functioned efficiently in vitro to catalyze site-specific cleavage of an artificial Holliday junction containing a dif site. Inactivation of codV alone did not cause a discernible change in phenotype, and it is speculated that RipX can substitute for CodV in vivo. PMID:10498718

  15. Refined positioning of a quantitative trait locus affecting somatic cell score on chromosome 18 in the German Holstein using linkage disequilibrium.

    PubMed

    Baes, C; Brand, B; Mayer, M; Kühn, C; Liu, Z; Reinhardt, F; Reinsch, N

    2009-08-01

    Combined linkage and linkage disequilibrium analysis (LALD) was conducted to more accurately map a previously reported quantitative trait locus (QTL) affecting somatic cell score on bovine chromosome 18. A grand-daughter design consisting of 6 German Holstein grandsire families with 1,054 progeny-tested genotyped sons was used in this study. Twenty microsatellite markers, 5 single nucleotide polymorphisms, and an erythrocyte antigen marker with an average marker spacing of 1.95 cM were analyzed along a chromosomal segment of 50.80 cM. Variance components were estimated and restricted maximum likelihood test statistics were calculated at the midpoint of each marker interval. The test statistics calculated in single-QTL linkage analysis exceeded the genome-wide significance threshold at several putative QTL positions. Using LALD, we were successful in assigning a genome-wide significant QTL to a confidence interval of 10.8 cM between the markers ILSTS002 and BMS833. The QTL in this marker interval was estimated to be responsible for between 5.89 and 13.86% of the genetic variation in somatic cell score. In contrast to the single-QTL linkage analysis model, LALD analyses with a 2-QTL model confirmed the position of one QTL, but gave no conclusive evidence for the existence or position of a second QTL. Ultimately, the QTL position was narrowed down considerably compared with previous results with a refined confidence interval of less than 11 cM. PMID:19620688

  16. 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.

  17. 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

  18. 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

  19. Mapping the locus of atrophia areata, a helicoid peripapillary chorioretinal degeneration with autosomal dominant inheritance, to chromosome 11p15.

    PubMed

    Fossdal, R; Magnússon, L; Weber, J L; Jensson, O

    1995-03-01

    Atrophia areata (AA) is an early onset autosomal dominant helicoid peripapillary chorioretinal degeneration, which was first demonstrated to be hereditary in an Icelandic family. It is characterized by bilateral wing-shaped atrophic areas of the retina, radiating from the optic disk. Primary complaints of affected individuals are due to refractive errors and scotomata associated with myopia which increases with age. A genome linkage search with 112 microsatellite DNA markers resulted in the highest probability of location for AA on chromosome 11. We genotyped 18 polymorphic markers on chromosome 11 and seven showed significant linkage to AA. The markers D11S1323 and D11S902 on 11p15 flank the region encompassing the gene for AA. PMID:7795606

  20. 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.

  1. 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.

  2. Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2

    PubMed Central

    Wong, Sunny H.; Owusu-Dabo, Ellis; Osei, Ivy; Gyapong, John; Sirugo, Giorgio; Sisay-Joof, Fatou; Enimil, Anthony; Chinbuah, Margaret A.; Floyd, Sian; Warndorff, David K.; Sichali, Lifted; Malema, Simon; Crampin, Amelia C.; Ngwira, Bagrey; Teo, Yik Y.; Small, Kerrin; Rockett, Kirk; Kwiatkowski, Dominic; Fine, Paul E.; Hill, Philip C.; Newport, Melanie; Lienhardt, Christian; Adegbola, Richard A.; Corrah, Tumani; Ziegler, Andreas; Morris, Andrew P.; Meyer, Christian G.

    2013-01-01

    We combined two tuberculosis (TB) genome-wide association studies (GWAS) from Ghana and The Gambia with subsequent replication totalling 11,425 participants. A significant association with disease was observed at SNP rs4331426 located in a gene-poor region on chromosome 18q11.2 (P=6.8×10−9, OR=1.19, 95%CI=1.13-1.27). Our finding shows that GWAS can identify novel loci for infectious causes of mortality even in Africa where levels of linkage disequilibrium are particularly low. PMID:20694014

  3. 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.

  4. 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.

  5. Cloning of the Koi Herpesvirus Genome as an Infectious Bacterial Artificial Chromosome Demonstrates That Disruption of the Thymidine Kinase Locus Induces Partial Attenuation in Cyprinus carpio koi▿

    PubMed Central

    Costes, B.; Fournier, G.; Michel, B.; Delforge, C.; Raj, V. Stalin; Dewals, B.; Gillet, L.; Drion, P.; Body, A.; Schynts, F.; Lieffrig, F.; Vanderplasschen, A.

    2008-01-01

    Koi herpesvirus (KHV) is the causative agent of a lethal disease in koi and common carp. In the present study, we describe the cloning of the KHV genome as a stable and infectious bacterial artificial chromosome (BAC) clone that can be used to produce KHV recombinant strains. This goal was achieved by the insertion of a loxP-flanked BAC cassette into the thymidine kinase (TK) locus. This insertion led to a BAC plasmid that was stably maintained in bacteria and was able to regenerate virions when permissive cells were transfected with the plasmid. Reconstituted virions free of the BAC cassette but carrying a disrupted TK locus (the FL BAC-excised strain) were produced by the transfection of Cre recombinase-expressing cells with the BAC. Similarly, virions with a wild-type revertant TK sequence (the FL BAC revertant strain) were produced by the cotransfection of cells with the BAC and a DNA fragment encoding the wild-type TK sequence. Reconstituted recombinant viruses were compared to the wild-type parental virus in vitro and in vivo. The FL BAC revertant strain and the FL BAC-excised strain replicated comparably to the parental FL strain. The FL BAC revertant strain induced KHV infection in koi carp that was indistinguishable from that induced by the parental strain, while the FL BAC-excised strain exhibited a partially attenuated phenotype. Finally, the usefulness of the KHV BAC for recombination studies was demonstrated by the production of an ORF16-deleted strain by using prokaryotic recombination technology. The availability of the KHV BAC is an important advance that will allow the study of viral genes involved in KHV pathogenesis, as well as the production of attenuated recombinant candidate vaccines. PMID:18337580

  6. Clinical aspects of an autosomal dominantly inherited hearing impairment linked to the DFNA60 locus on chromosome 2q23.1-2q23.3.

    PubMed

    van Beelen, E; Schraders, M; Huygen, P L M; Oostrik, J; Plantinga, R F; van Drunen, W; Collin, R W J; Kooper, D P; Pennings, R J E; Cremers, C W R J; Kremer, H; Kunst, H P M

    2013-06-01

    A total of 64 loci for autosomal dominant non-syndromic hearing impairment have been described, and the causative genes have been identified for 24 of these. The present study reports on the clinical characteristics of an autosomal dominantly inherited hearing impairment that is linked to a region within the DFNA60 locus located on chromosome 2 in q22.1-24.1. A pedigree spanning four generations was established with 13 affected individuals. Linkage analysis demonstrated that the locus extended over a 2.96 Mb region flanked by markers D2S2335 and D2S2275. The audiograms mainly showed a distinctive U-shaped configuration. Deterioration of hearing started at a wide age range, from 12 to 40 years. Cross-sectional analysis showed rapid progression of hearing impairment from mild to severe, between the ages of 40 and 60 years, a phenomenon that is also observed in DFNA9 patients. The results of the individual longitudinal analyses were generally in line with those obtained by the cross-sectional analysis. Speech recognition scores related to the level of hearing impairment (PTA1,2,4 kHz) appeared to be fairly similar to those of presbyacusis patients. It is speculated that hearing impairment starting in mid-life, as shown by DFNA60 patients, could play a role in the development of presbyacusis. Furthermore, speech recognition did not deteriorate appreciably before the sixth decade of life. We conclude that DFNA60 should be considered in hearing impaired patients who undergo a rapid progression in middle age and are negative for DFNA9. Furthermore, cochlear implantation resulted in good rehabilitation in two DFNA60 patients. PMID:23538131

  7. 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

  8. Evidence for a chromosome 2p13-14 schizophrenia susceptibility locus in families from Palau, Micronesia.

    PubMed

    Coon, H; Myles-Worsley, M; Tiobech, J; Hoff, M; Rosenthal, J; Bennett, P; Reimherr, F; Wender, P; Dale, P; Polloi, A; Byerley, W

    1998-11-01

    A large multiplex schizophrenia pedigree ascertained from the Micronesian nation of Palau was genotyped with 406 microsatellite DNA markers evenly distributed throughout the genome. Assuming autosomal dominant inheritance, the highest genome-wide lod scores were found for DNA loci mapping to 2p13-14; the maximum lod score was 2.17 (theta = 0.05) at D2S441. A nonparametric APM analysis was also suggestive at D2S441 (APM score = 2.96, P = 0.011). Of the 14 affected cases in this extended family, eight share a large haplotype in this region spanning approximately 11 cM. When 16 other families containing 65 schizophrenic cases were typed in a follow-up study of this region, the maximum lod score remained positive (maximum at D2S441 1.69, theta = 0.20). APM results also remained positive at D2S441 for all 17 families (APM score = 4.87, P = 0.0006). The linkage and haplotype sharing results provide suggestive evidence for a 2p locus predisposing to schizophrenia in a subset of families in the Palauan population. PMID:9857978

  9. cDNA cloning and gene structure of a novel water channel expressed exclusively in human kidney: Evidence for a gene cluster of aquaporins at chromosome locus 12q13

    SciTech Connect

    Ma, Tonghui; Yang, Baoxue; Verkman, A.S.

    1996-08-01

    A 1.8-kb cDNA clone (designed hKID, gene symbol AQP2L) with homology to the aquaporins was isolated from a human kidney cDNA library. The longest open reading frame of 846 bp encoded a 282-amino-acid hydrophobic protein that contained the conserved NPA motifs of MIP family members. Cell-free translation produced a nonglycosylated protein migrating at 29 kDa. Northern blot analysis revealed a 2.2-kb transcript expressed only in human kidney. PCR/Southern blot analysis of human kidney cDNA using primers flanking the hKID coding sequence revealed expression of a full-length mRNA and short transcripts with partial exon 1 and partial exon 4 deletions. Genomic Southern blot indicted a single-copy hKID gene. PCR analysis of a human/rodent somatic hybrid panel localized the hKID gene to chromosome 12. Chromosomal fluorescence in situ hybridization mapped the hKID (AQP2L) gene to chromosome locus 12q13, the same location a as the AQP-2 and MIP genes. The high sequence homology, similar genomic structure, and identical chromosomal loci of hKID, MIP, and AQP-2 suggest a MIP family gene cluster at chromosome locus 12q13. Further work is needed to establish the physiological significance of hKID. 43 refs., 6 figs.

  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-wide and fine-mapping linkage studies of type 2 diabetes and glucose traits in the Old Order Amish: evidence for a new diabetes locus on chromosome 14q11 and confirmation of a locus on chromosome 1q21-q24.

    PubMed

    Hsueh, Wen-Chi; St Jean, Pamela L; Mitchell, Braxton D; Pollin, Toni I; Knowler, William C; Ehm, Margaret G; Bell, Callum J; Sakul, Hakan; Wagner, Michael J; Burns, Daniel K; Shuldiner, Alan R

    2003-02-01

    We conducted a genome scan using a 10-cM map to search for genes linked to type 2 diabetes in 691 individuals from a founder population, the Old Order Amish. We then saturated two regions on chromosomes 1 and 14 showing promising linkage signals with additional markers to produce a approximately 2-cM map for fine mapping. Analyses of both discrete traits (type 2 diabetes and the composite trait of type 2 diabetes and/or impaired glucose homeostasis [IGH]), and quantitative traits (glucose levels during a 75-g oral glucose challenge, designated glucose 0-180 and HbA(1c)) were performed. We obtained significant evidence for linkage to type 2 diabetes in a novel region on chromosome 14q11 (logarithm of odds [LOD] for diabetes = 3.48, P = 0.00005). Furthermore, we observed evidence for the existence of a diabetes-related locus on chromosome 1q21-q24 (LOD for type 2 diabetes/IGH = 2.35, P = 0.0008), a region shown to be linked to diabetes in several other studies. Suggestive evidence for linkage to glucose traits was observed on three other regions: 14q11-q13 (telomeric to that above with LOD = 1.82-1.85 for glucose 150 and 180), 1p31 (LOD = 1.28-2.30 for type 2 diabetes and glucose 120-180), and 18p (LOD = 3.07, P = 0.000085 for HbA(1c) and LOD = 1.50 for glucose 0). In conclusion, our findings provide evidence that type 2 diabetes susceptibility genes reside on chromosomes 1, 14, and 18. PMID:12540634

  12. A 4.5-megabase yeast artificial chromosome contig from human chromosome 13q14.3 ordering 9 polymorphic microsatellites (22 sequence-tagged sites) tightly linked to the Wilson disease locus.

    PubMed Central

    White, A; Tomfohrde, J; Stewart, E; Barnes, R; Le Paslier, D; Weissenbach, J; Cavalli-Sforza, L; Farrer, L; Bowcock, A

    1993-01-01

    We have previously performed a genetic analysis of multiply affected families to map a locus responsible for Wilson disease (WND) to a 0.3-centimorgan (cM) region within chromosome 13q14.3, between D13S31 and D13S59. Here we describe the construction of a contig of approximately 4.5 Mb, which spans this region and extends from D13S25 to D13S59. This contig consists of 28 genomic yeast artificial chromosome (YAC) clones. Five critical crossover events have been defined in this interval in two unaffected (Centre d'Etudes du Polymorphisme Humain) and three WND families. The combination of sequence tagged site content mapping of YACs with both polymorphic and nonpolymorphic markers and recombination breakpoint mapping resulted in the following order of polymorphic markers: centromere-RB1-D13S25-AFM205vh2-D13S31-D13S22 7-D13S228-AFM238vc3-D13S133- AFM084xc5-D13S137-D13S169, D13S155-D13S59-telomere. The recombination/physical distance ratio varies from approximately 3000 kb per cM in the region between D13S31 and D13S25 to 6000 kb per cM in the region between D13S31 and D13S59. Three WND families exhibiting recombination between the disease locus and D13S31 or D13S59 were genotyped for additional markers in this region and further refined the location of the WND gene to between D13S155 and D13S133. Nine of the markers in this region of < 1 cM are polymorphic microsatellites (seven have observed heterozygosities of 70% or above) that will be extremely useful in prenatal and preclinical diagnosis of this disease. This physical map is an essential step in the isolation of the WND gene and is a framework for the identification of candidate genes. PMID:8234264

  13. 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.

  14. A functional AT/G polymorphism in the 5'-untranslated region of SETDB2 in the IgE locus on human chromosome 13q14.

    PubMed

    Holt, R J; Vandiedonck, C; Willis-Owen, S A; Knight, J C; Cookson, W O; Moffatt, M F; Zhang, Y

    2015-10-01

    The immunoglobulin E (IgE)-associated locus on human chromosome 13q14 influencing asthma-related traits contains the genes PHF11 and SETDB2. SETDB2 is located in the same linkage disequilibrium region as PHF11 and polymorphisms within SETDB2 have been shown to associate with total serum IgE levels. In this report, we sequenced the 15 exons of SETDB2 and identified a single previously ungenotyped mutation (AT/G, rs386770867) in the 5'-untranslated region of the gene. The polymorphism was found to be significantly associated with serum IgE levels in our asthma cohort (P=0.0012). Electrophoretic mobility shift assays revealed that the transcription factor Ying Yang 1 binds to the AT allele, whereas SRY (Sex determining Region Y) binds to the G allele. Allele-specific transcription analysis (allelotyping) was performed in 35 individuals heterozygous for rs386770867 from a panel of 200 British families ascertained through probands with severe stage 3 asthma. The AT allele was found to be significantly overexpressed in these individuals (P=1.26×10(-21)). A dual-luciferase assay with the pGL3 luciferase reporter gene showed that the AT allele significantly affects transcriptional activities. Our results indicate that the IgE-associated AT/G polymorphism (rs386770867) regulates transcription of SETDB2. PMID:26378653

  15. Aod1, the immunoregulatory locus controlling abrogation of tolerance in neonatal thymectomy-induced autoimmune ovarian dysgenesis, maps to mouse chromosome 16.

    PubMed Central

    Wardell, B B; Michael, S D; Tung, K S; Todd, J A; Blankenhorn, E P; McEntee, K; Sudweeks, J D; Hansen, W K; Meeker, N D; Griffith, J S

    1995-01-01

    Mice thymectomized at three days of age (D3Tx) develop during adulthood a variety of organ-specific autoimmune diseases, including autoimmune ovarian dysgenesis (AOD). The phenotypic spectrum of AOD is characterized by the development of anti-ovarian autoantibodies, oophoritis, and atrophy. The D3Tx model of AOD is unique in that disease induction depends exclusively on perturbation of the normal developing immune system, is T-cell-mediated, and is strain specific. For example, D3Tx A/J mice are highly susceptible to AOD, whereas C57BL/6J mice are resistant. After D3Tx, self ovarian antigens, expressed at physiological levels, trigger an autoimmune response capable of eliciting disease. The D3Tx model provides, therefore, the opportunity to focus on the mechanisms of self-tolerance that are relevant to disease pathogenesis. Previous studies indicate that the principal mechanisms involved in AOD susceptibility are genetically controlled and govern developmental processes associated with the induction and maintenance of peripheral tolerance. We report here the mapping of the Aod1 locus to mouse chromosome 16 within a region encoding several loci of immunologic relevance, including scid, Igl1, VpreB, Igll, Igl1r, Mtv6 (Mls-3), Ly-7, Ifnar, and Ifgt. Images Fig. 1 Fig. 2 PMID:7761397

  16. Characterization of a kinesin-related gene ATSV, within the tuberous sclerosis locus (TSC1) candidate region on chromosome 9q34

    SciTech Connect

    Furlong, R.A.; Zhou, Chun Yan; Ferguson-Smith, M.A.; Affara, N.A.

    1996-05-01

    In the search for candidate genes for the tuberous sclerosis (TSC1) disease locus on chromosome 9q34, we have isolated an overlapping series of 22 plasmid and phage cDNA clones covering nearly 7 kb and with an open reading frame of 5070 bp encoding a protein of 1690 amino acids. The putative protein product is a member of the kinesin superfamily and is homologous to the mouse KIF1A and the Caenorhabditas elegans unc-104 genes. Both KIF1A and unc-104 function in the anterograde axonal transport of synaptic vesicles. The human homolog is therefore termed H-ATSV (axonal transporter of synaptic vesicles, HGMW-approved nomenclature ATSV). Screening of DNA from 107 tuberous sclerosis patients and 80 unaffected individuals with H-ATSV cDNA probes by pulsed-field gel electrophoresis/Southern blotting following digestion by rare-cutting methylation-sensitive restriction enzymes showed variant banding patterns in three patients with tuberous sclerosis. However, further analysis indicated that these variant fragments represent a rare polymorphism probably associated with methylation of clustered restriction sites. There is no evidence to support H-ATSV as a candidate gene for TSC1. 28 refs., 5 figs.

  17. Physical and transcript map of the autosomal dominant colobomatous microphthalmia locus on chromosome 15q12-q15 and refinement to a 4.4 Mb region.

    PubMed

    Michon, Laetitia; Morlé, Laurette; Bozon, Muriel; Duret, Laurent; Zech, Jean-Christophe; Godet, Jacqueline; Plauchu, Henry; Edery, Patrick

    2004-07-01

    Congenital microphthalmia is a developmental disorder characterized by shortened axial length of the eye. We have previously mapped the gene responsible for autosomal dominant colobomatous microphthalmia in a 5-generation family to chromosome 15q12-q15. Here, we set up a physical and transcript map of the 13.8 cM critical region, flanked by loci D15S1002 and D15S1040. Physical mapping and genetic linkage analysis using 20 novel polymorphic markers allowed the refinement of the disease locus to two intervals in close vicinity, namely a centromeric interval, bounded by microsatellite DNA markers m3-m17, and a telomeric interval, m76-m24, encompassing respectively 1.9 and 2.5 Mb. Moreover, we excluded three candidate genes, CKTSF1B1, KLF13 and CX36. Finally, although a phenomenon of anticipation was suggested by phenotypic and pedigree data, no abnormal expansion of three trinucleotide repeats mapping to the refine interval was found in affected individuals. PMID:15083168

  18. A functional AT/G polymorphism in the 5′-untranslated region of SETDB2 in the IgE locus on human chromosome 13q14

    PubMed Central

    Holt, R J; Vandiedonck, C; Willis-Owen, S A; Knight, J C; Cookson, W O; Moffatt, M F; Zhang, Y

    2015-01-01

    The immunoglobulin E (IgE)-associated locus on human chromosome 13q14 influencing asthma-related traits contains the genes PHF11 and SETDB2. SETDB2 is located in the same linkage disequilibrium region as PHF11 and polymorphisms within SETDB2 have been shown to associate with total serum IgE levels. In this report, we sequenced the 15 exons of SETDB2 and identified a single previously ungenotyped mutation (AT/G, rs386770867) in the 5′-untranslated region of the gene. The polymorphism was found to be significantly associated with serum IgE levels in our asthma cohort (P=0.0012). Electrophoretic mobility shift assays revealed that the transcription factor Ying Yang 1 binds to the AT allele, whereas SRY (Sex determining Region Y) binds to the G allele. Allele-specific transcription analysis (allelotyping) was performed in 35 individuals heterozygous for rs386770867 from a panel of 200 British families ascertained through probands with severe stage 3 asthma. The AT allele was found to be significantly overexpressed in these individuals (P=1.26 × 10−21). A dual-luciferase assay with the pGL3 luciferase reporter gene showed that the AT allele significantly affects transcriptional activities. Our results indicate that the IgE-associated AT/G polymorphism (rs386770867) regulates transcription of SETDB2. PMID:26378653

  19. 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.

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

    PubMed

    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

    2006-01-01

    Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for approximately 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

  1. 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

  2. Linkage Disequilibrium Mapping of the Chromosome 6q21–22.31 Bipolar I Disorder Susceptibility Locus

    PubMed Central

    Fan, Jinbo; Ionita-Laza, Iuliana; McQueen, Matthew B.; Devlin, Bernie; Purcell, Shaun; Faraone, Stephen V.; Allen, Michael H.; Bowden, Charles L.; Calabrese, Joseph R.; Fossey, Mark D.; Friedman, Edward S.; Gyulai, Laszlo; Hauser, Peter; Ketter, Terence B.; Marangell, Lauren B.; Miklowitz, David J.; Nierenberg, Andrew A.; Patel, Jayendra K.; Sachs, Gary S.; Thase, Michael E.; Molay, Francine B.; Escamilla, Michael A.; Nimgaonkar, Vishwajit L.; Sklar, Pamela; Laird, Nan M.; Smoller, Jordan W.

    2014-01-01

    We previously reported genome-wide significant evidence for linkage between chromosome 6q and bipolar I disorder (BPI) by performing a meta-analysis of original genotype data from 11 genome scan linkage studies. We now present follow-up linkage disequilibrium mapping of the linked region utilizing 3,047 single nucleotide polymorphism (SNP) markers in a case–control sample (N = 530 cases, 534 controls) and family-based sample (N = 256 nuclear families, 1,301 individuals). The strongest single SNP result (rs6938431, P=6.72× 10−5) was observed in the case–control sample, near the solute carrier family 22, member 16 gene (SLC22A16). In a replication study, we genotyped 151 SNPs in an independent sample (N = 622 cases, 1,181 controls) and observed further evidence of association between variants at SLC22A16 and BPI. Although consistent evidence of association with any single variant was not seen across samples, SNP-wise and gene-based test results in the three samples provided convergent evidence for association with SLC22A16, a carnitine transporter, implicating this gene as a novel candidate for BPI risk. Further studies in larger samples are warranted to clarify which, if any, genes in the 6q region confer risk for bipolar disorder. PMID:19308960

  3. Identification of Soat1 as a quantitative trait locus gene on mouse chromosome 1 contributing to hyperlipidemia.

    PubMed

    Lu, Zongji; Yuan, Zuobiao; Miyoshi, Toru; Wang, Qian; Su, Zhiguang; Chang, Catherine C; Shi, Weibin

    2011-01-01

    We previously identified two closely linked quantitative trait loci (QTL) on distal chromosome 1 contributing to major variations in plasma cholesterol and triglyceride levels in an intercross derived from C57BL/6 (B6) and C3H/HeJ (C3H) apolipoprotein E-deficient (apoE(-/-)) mice. Soat1, encoding sterol o-acyltransferase 1, is a functional candidate gene located underneath the proximal linkage peak. We sequenced the coding region of Soat1 and identified four single nucleotide polymorphisms (SNPs) between B6 and C3H mice. Two of the SNPs resulted in amino-acid substitutions (Ile147Val and His205Tyr). Functional assay revealed an increased enzyme activity of Soat1 in peritoneal macrophages of C3H mice relative to those of B6 mice despite comparable protein expression levels. Allelic variants of Soat1 were associated with variations in plasma cholesterol and triglyceride levels in an intercross between B6.apoE(-/-) and C3H.apoE(-/-) mice. Inheritance of the C3H allele resulted in significantly higher plasma lipid levels than inheritance of the B6 allele. Soat1 variants were also significantly linked to major variations in plasma esterified cholesterol levels but not with free cholesterol levels. Trangenic expression of C3H Soat1 in B6.apoE(-/-) mice resulted in elevations of plasma cholesterol and triglyceride levels. These results indicate that Soat1 is a QTL gene contributing to hyperlipidemia. PMID:22022387

  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. The Cnes2 Locus on Mouse Chromosome 17 Regulates Host Defense against Cryptococcal Infection through Pleiotropic Effects on Host Immunity

    PubMed Central

    Shourian, Mitra; Flaczyk, Adam; Angers, Isabelle; Mindt, Barbara C.; Fritz, Jörg H.

    2015-01-01

    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. PMID:26371125

  6. Genetic heterogeneity in familial acute myelogenous leukemia: evidence for a second locus at chromosome 16q21-23.2.

    PubMed Central

    Horwitz, M; Benson, K F; Li, F Q; Wolff, J; Leppert, M F; Hobson, L; Mangelsdorf, M; Yu, S; Hewett, D; Richards, R I; Raskind, W H

    1997-01-01

    The identification of genes responsible for the rare cases of familial leukemia may afford insight into the mechanism underlying the more common sporadic occurrences. Here we test a single family with 11 relevant meioses transmitting autosomal dominant acute myelogenous leukemia (AML) and myelodysplasia for linkage to three potential candidate loci. In a different family with inherited AML, linkage to chromosome 21q22.1-22.2 was recently reported; we exclude linkage to 21q22.1-22.2, demonstrating that familial AML is a heterogeneous disease. After reviewing familial leukemia and observing anticipation in the form of a declining age of onset with each generation, we had proposed 9p21-22 and 16q22 as additional candidate loci. Whereas linkage to 9p21-22 can be excluded, the finding of a maximum two-point LOD score of 2.82 with the microsatellite marker D16S522 at a recombination fraction theta = 0 provides evidence supporting linkage to 16q22. Haplotype analysis reveals a 23.5-cM (17.9-Mb) commonly inherited region among all affected family members extending from D16S451 to D16S289. In order to extract maximum linkage information with missing individuals, incomplete informativeness with individual markers in this interval, and possible deviance from strict autosomal dominant inheritance, we performed nonparametric linkage analysis (NPL) and found a maximum NPL statistic corresponding to a P-value of .00098, close to the maximum conditional probability of linkage expected for a pedigree with this structure. Mutational analysis in this region specifically excludes expansion of the AT-rich minisatellite repeat FRA16B fragile site and the CAG trinucleotide repeat in the E2F-4 transcription factor. The "repeat expansion detection" method, capable of detecting dynamic mutation associated with anticipation, more generally excludes large CAG repeat expansion as a cause of leukemia in this family. Images Figure 2 Figure 4 PMID:9382098

  7. 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

  8. High-Resolution Mapping of a Genetic Locus Regulating Preferential Carbohydrate Intake, Total Kilocalories, and Food Volume on Mouse Chromosome 17

    PubMed Central

    Gularte-Mérida, Rodrigo; DiCarlo, Lisa M.; Robertson, Ginger; Simon, Jacob; Johnson, William D.; Kappen, Claudia; Medrano, Juan F.; Richards, Brenda K.

    2014-01-01

    The specific genes regulating the quantitative variation in macronutrient preference and food intake are virtually unknown. We fine mapped a previously identified mouse chromosome 17 region harboring quantitative trait loci (QTL) with large effects on preferential macronutrient intake-carbohydrate (Mnic1), total kilcalories (Kcal2), and total food volume (Tfv1) using interval-specific strains. These loci were isolated in the [C57BL/6J.CAST/EiJ-17.1-(D17Mit19-D17Mit50); B6.CAST-17.1] strain, possessing a ∼40.1 Mb region of CAST DNA on the B6 genome. In a macronutrient selection paradigm, the B6.CAST-17.1 subcongenic mice eat 30% more calories from the carbohydrate-rich diet, ∼10% more total calories, and ∼9% more total food volume per body weight. In the current study, a cross between carbohydrate-preferring B6.CAST-17.1 and fat-preferring, inbred B6 mice was used to generate a subcongenic-derived F2 mapping population; genotypes were determined using a high-density, custom SNP panel. Genetic linkage analysis substantially reduced the 95% confidence interval for Mnic1 (encompassing Kcal2 and Tfv1) from 40.1 to 29.5 Mb and more precisely established its boundaries. Notably, no genetic linkage for self-selected fat intake was detected, underscoring the carbohydrate-specific effect of this locus. A second key finding was the separation of two energy balance QTLs: Mnic1/Kcal2/Tfv1 for food intake and a newly discovered locus regulating short term body weight gain. The Mnic1/Kcal2/Tfv1 QTL was further de-limited to 19.0 Mb, based on the absence of nutrient intake phenotypes in subcongenic HQ17IIa mice. Analyses of available sequence data and gene ontologies, along with comprehensive expression profiling in the hypothalamus of non-recombinant, cast/cast and b6/b6 F2 controls, focused our attention on candidates within the QTL interval. Zfp811, Zfp870, and Btnl6 showed differential expression and also contain stop codons, but have no known biology related to food

  9. Genetic and functional evidence for a locus controlling otitis media at chromosome 10q26.3

    PubMed Central

    2014-01-01

    7922424; r2 = 0.97) alters a transcription factor binding site (CREB/CREBP) in the intergenic region between TCERG1L and PPP2R2D. Conclusions OM linkage was replicated at 10q26.3. Whilst multiple genes could contribute to this linkage, the weight of evidence supports PPP2R2D, a TGF-β/Activin/Nodal pathway modulator, as the more likely functional candidate lying immediately under the linkage peak for OM susceptibility at chromosome 10q26.3. PMID:24499112

  10. Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease.

    PubMed

    Johnson, Matthew P; Brennecke, Shaun P; East, Christine E; Dyer, Thomas D; Roten, Linda T; Proffitt, J Michael; Melton, Phillip E; Fenstad, Mona H; Aalto-Viljakainen, Tia; Mäkikallio, Kaarin; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K

    2013-07-01

    Pre-eclampsia is an idiopathic pregnancy disorder promoting morbidity and mortality to both mother and child. Delivery of the fetus is the only means to resolve severe symptoms. Women with pre-eclamptic pregnancies demonstrate increased risk for later life cardiovascular disease (CVD) and good evidence suggests these two syndromes share several risk factors and pathophysiological mechanisms. To elucidate the genetic architecture of pre-eclampsia we have dissected our chromosome 2q22 susceptibility locus in an extended Australian and New Zealand familial cohort. Positional candidate genes were prioritized for exon-centric sequencing using bioinformatics, SNPing, transcriptional profiling and QTL-walking. In total, we interrogated 1598 variants from 52 genes. Four independent SNP associations satisfied our gene-centric multiple testing correction criteria: a missense LCT SNP (rs2322659, P = 0.0027), a synonymous LRP1B SNP (rs35821928, P = 0.0001), an UTR-3 RND3 SNP (rs115015150, P = 0.0024) and a missense GCA SNP (rs17783344, P = 0.0020). We replicated the LCT SNP association (P = 0.02) and observed a borderline association for the GCA SNP (P = 0.07) in an independent Australian case-control population. The LRP1B and RND3 SNP associations were not replicated in this same Australian singleton cohort. Moreover, these four SNP associations could not be replicated in two additional case-control populations from Norway and Finland. These four SNPs, however, exhibit pleiotropic effects with several quantitative CVD-related traits. Our results underscore the genetic complexity of pre-eclampsia and present novel empirical evidence of possible shared genetic mechanisms underlying both pre-eclampsia and other CVD-related risk factors. PMID:23420841

  11. Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study.

    PubMed

    Assimes, Themistocles L; Knowles, Joshua W; Basu, Analabha; Iribarren, Carlos; Southwick, Audrey; Tang, Hua; Absher, Devin; Li, Jun; Fair, Joan M; Rubin, Geoffrey D; Sidney, Stephen; Fortmann, Stephen P; Go, Alan S; Hlatky, Mark A; Myers, Richard M; Risch, Neil; Quertermous, Thomas

    2008-08-01

    A susceptibility locus for coronary artery disease (CAD) at chromosome 9p21 has recently been reported, which may influence the age of onset of CAD. We sought to replicate these findings among white subjects and to examine whether these results are consistent with other racial/ethnic groups by genotyping three single nucleotide polymorphisms (SNPs) in the risk interval in the Atherosclerotic Disease, Vascular Function, and Genetic Epidemiology (ADVANCE) study. One or more of these SNPs was associated with clinical CAD in whites, U.S. Hispanics and U.S. East Asians. None of the SNPs were associated with CAD in African Americans although the power to detect an odds ratio (OR) in this group equivalent to that seen in whites was only 24-30%. ORs were higher in Hispanics and East Asians and lower in African Americans, but in all groups the 95% confidence intervals overlapped with ORs observed in whites. High-risk alleles were also associated with increased coronary artery calcification in controls and the magnitude of these associations by racial/ethnic group closely mirrored the magnitude observed for clinical CAD. Unexpectedly, we noted significant genotype frequency differences between male and female cases (P = 0.003-0.05). Consequently, men tended towards a recessive and women tended towards a dominant mode of inheritance. Finally, an effect of genotype on the age of onset of CAD was detected but only in men carrying two versus one or no copy of the high-risk allele and presenting with CAD at age >50 years. Further investigations in other populations are needed to confirm or refute our findings. PMID:18443000

  12. 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.

  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. 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

  15. 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

  16. 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.

  17. 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.

  18. The IGF2 Locus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin-like growth factor 2 (IGF2) is a peptide hormone regulating various cellular processes such as proliferation and apoptosis. IGF2 is vital to embryo development. The IGF2 locus covers approximately 150-kb genomic region on human chromosome 11, containing two imprinted genes, IGF2 and H19, sha...

  19. Accuracy and coverage assessment of Oryctolagus cuniculus (Rabbit) Genes Encoding Immunoglobulins in the Whole Genome Sequence Assembly (OryCun2.0) and Localization of the IGH Locus to Chromosome 20

    PubMed Central

    Gertz, E. Michael; Schäffer, Alejandro A.; Agarwala, Richa; Bonnet-Garnier, Amélie; Rogel-Gaillard, Claire; Hayes, Hélène; Mage, Rose G.

    2013-01-01

    We report analyses of genes encoding immunoglobulin heavy and light chains in the rabbit 6.51x whole genome assembly. This OryCun2.0 assembly confirms previous mapping of the duplicated IGK1 and IGK2 loci to chromosome 2 and the IGL lambda light chain locus to chromosome 21. The most frequently rearranged and expressed IGHV1 that is closest to IG DH and IGHJ genes encodes rabbit VHa allotypes. The partially inbred Thorbecke strain rabbit used for whole-genome sequencing was homozygous at the IGK but heterozygous with the IGHV1a1 allele in one of 79 IGHV-containing unplaced scaffolds and IGHV1a2, IGHM, IGHG and IGHE sequences in another. Some IGKV, IGLV and IGHA genes are also in other unplaced scaffolds. By fluorescence in situ hybridization, we assigned the previously unmapped IGH locus to the q-telomeric region of rabbit chromosome 20. An approximately 3 Mb segment of human chromosome 14 including IGH genes predicted to map to this telomeric region based on synteny analysis could not be located on assembled chromosome 20. Unplaced scaffold chrUn0053 contains some of the genes that comparative mapping predicts to be missing. We identified discrepancies between previous targeted studies and the OryCun2.0 assembly and some new BAC clones with IGH sequences that can guide other studies to further sequence and improve the OryCun2.0 assembly. Complete knowledge of gene sequences encoding variable regions of rabbit heavy, kappa and lambda chains will lead to better understanding of how and why rabbits produce antibodies of high specificity and affinity through gene conversion and somatic hypermutation. PMID:23925440

  20. 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

  1. 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.

  2. 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.

  3. A Genomewide Scan for Loci Predisposing to Type 2 Diabetes in a U.K. Population (The Diabetes UK Warren 2 Repository): Analysis of 573 Pedigrees Provides Independent Replication of a Susceptibility Locus on Chromosome 1q

    PubMed Central

    Wiltshire, Steven; Hattersley, Andrew T.; Hitman, Graham A.; Walker, Mark; Levy, Jonathan C.; Sampson, Michael; O’Rahilly, Stephen; Frayling, Timothy M.; Bell, John I.; Lathrop, G. Mark; Bennett, Amanda; Dhillon, Ranjit; Fletcher, Christopher; Groves, Christopher J.; Jones, Elizabeth; Prestwich, Philip; Simecek, Nikol; Rao, Pamidighantam V. Subba; Wishart, Marie; Foxon, Richard; Howell, Simon; Smedley, Damian; Cardon, Lon R.; Menzel, Stephan; McCarthy, Mark I.

    2001-01-01

    Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores ⩾1.18 (P⩽.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest. PMID:11484155

  4. 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

  5. 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.

  6. 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

  7. Identification of quantitative trait locus for abscisic acid responsiveness on chromosome 5A and association with dehydration tolerance in common wheat seedlings.

    PubMed

    Iehisa, Julio C M; Matsuura, Takakazu; Mori, Izumi C; Takumi, Shigeo

    2014-01-15

    The phytohormone abscisic acid (ABA) plays important roles in response to environmental stress as well as in seed maturation and dormancy. In common wheat, quantitative trait loci (QTLs) for ABA responsiveness at the seedling stage have been reported on chromosomes 1B, 2A, 3A, 6D and 7B. In this study, we identified a novel QTL for ABA responsiveness on chromosome 5A using an F2 population derived from a cross between the common wheat cultivar Chinese Spring (CS) and a chromosome substitution line of CS with chromosome 5A of cultivar Hope (Hope5A). This QTL was found in a similar chromosomal region to previously reported QTLs for drought tolerance and seed dormancy. Physiological characterization of the QTL revealed a small effect on dehydration tolerance and seed dormancy. The rate of water loss from leaves during dehydration was lower, and transcript accumulation of the cold responsive (COR)/late embryogenesis abundant (LEA) genes Wrab18 and Wdhn13 tended to be higher under dehydration stress in F2 individuals carrying the Hope allele of the QTL, which also showed higher ABA responsiveness than the CS allele-carrying individuals. Seed dormancy of individuals carrying the Hope allele also tended to be lower than those carrying the CS allele. Our results suggest that variation in ABA responsiveness among common wheat cultivars is at least partly determined by the 5A QTL, and that this QTL contributes to development of dehydration and preharvest sprouting tolerance. PMID:24331416

  8. 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

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

    PubMed

    Murga-Zamalloa, Carlos; Guevara-Fujita, Maria Luisa; Estrada-Cuzcano, Alejandro; Fujita, Ricardo

    2009-10-01

    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

  10. New assignment of the adenosine deaminase gene locus to chromosome 20q13 X 11 by study of a patient with interstitial deletion 20q.

    PubMed Central

    Petersen, M B; Tranebjaerg, L; Tommerup, N; Nygaard, P; Edwards, H

    1987-01-01

    A karyotype 46,XY,del(20)(q11 X 23q13 X 11) was found in a three year old boy with mental and growth retardation, low set ears, broad nasal bridge, and macrostomia. Adenosine deaminase (ADA) activity was reduced by about 50%, assigning the gene locus to the deleted segment. A review of the previously reported regional assignments suggests that the ADA gene is in the region of band 20q13 X 11. Images PMID:3560174

  11. Family-based study shows heterogeneity of a susceptibility locus on chromosome 8q24 for nonsyndromic cleft lip and palate

    PubMed Central

    Blanton, Susan H.; Burt, Amber; Stal, Samuel; Mulliken, John B.; Garcia, Elizabeth; Hecht, Jacqueline T.

    2010-01-01

    BACKGROUND Nonsyndromic cleft lip with or without cleft palate is a common birth defect. While a number of susceptibility loci have been reported, replication has often been lacking. This is likely due, in part, to heterogeneity of datasets and methodologies employed. Two independent genome-wide association studies of individuals of largely western European extraction have identified a possible susceptibility locus on 8q24.21. METHODS In order to determine the overall impact of this locus, we genotyped six of the previously associated SNPs in our Hispanic and nonHispanic white family-based datasets and evaluated them for linkage and association. In addition, we genotyped a large African-American NSCLP family that we had previously mapped to the 8q21.3-24.12 region to test for linkage. RESULTS There was no evidence for linkage to this region in any of the three ethnic groups. Nevertheless, strong evidence for association was noted in the nonHispanic white group, whereas none was detected in the Hispanic dataset. CONCLUSION These results confirm the previously reported association and provide evidence suggesting that there is ethnically-based heterogeneity for this locus. PMID:20196142

  12. A high-resolution map of the Grp1 locus on chromosome V of potato harbouring broad-spectrum resistance to the cyst nematode species Globodera pallida and Globodera rostochiensis.

    PubMed

    Finkers-Tomczak, Anna; Danan, Sarah; van Dijk, Thijs; Beyene, Amelework; Bouwman, Liesbeth; Overmars, Hein; van Eck, Herman; Goverse, Aska; Bakker, Jaap; Bakker, Erin

    2009-06-01

    The Grp1 locus confers broad-spectrum resistance to the potato cyst nematode species Globodera pallida and Globodera rostochiensis and is located in the GP21-GP179 interval on the short arm of chromosome V of potato. A high-resolution map has been developed using the diploid mapping population RHAM026, comprising 1,536 genotypes. The flanking markers GP21 and GP179 have been used to screen the 1,536 genotypes for recombination events. Interval mapping of the resistances to G. pallida Pa2 and G. rostochiensis Ro5 resulted in two nearly identical LOD graphs with the highest LOD score just north of marker TG432. Detailed analysis of the 44 recombinant genotypes showed that G. pallida and G. rostochiensis resistance could not be separated and map to the same location between marker SPUD838 and TG432. It is suggested that the quantitative resistance to both nematode species at the Grp1 locus is mediated by one or more tightly linked R genes that might belong to the NBS-LRR class. PMID:19363662

  13. 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

  14. Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4.

    PubMed Central

    Mehenni, H; Blouin, J L; Radhakrishna, U; Bhardwaj, S S; Bhardwaj, K; Dixit, V B; Richards, K F; Bermejo-Fenoll, A; Leal, A S; Raval, R C; Antonarakis, S E

    1997-01-01

    Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease with variable expression and incomplete penetrance, characterized by mucocutaneous pigmentation and hamartomatous polyposis. Patients with PJS have increased frequency of gastrointestinal and extraintestinal malignancies (ovaries, testes, and breast). In order to map the locus (or loci) associated with PJS, we performed a genomewide linkage analysis, using DNA polymorphisms in six families (two from Spain, two from India, one from the United States, and one from Portugal) comprising a total of 93 individuals, including 39 affected and 48 unaffected individuals and 6 individuals with unknown status. During this study, localization of a PJS gene to 19p13.3 (around marker D19S886) had been reported elsewhere. For our families, marker D19S886 yielded a maximum LOD score of 4.74 at a recombination fraction (theta) of .045; multipoint linkage analysis resulted in a LOD score of 7.51 for the interval between D19S886 and 19 pter. However, markers on 19q13.4 also showed significant evidence for linkage. For example, D19S880 resulted in a maximum LOD score of 3.8 at theta = .13. Most of this positive linkage was contributed by a single family, PJS07. These results confirm the mapping of a common PJS locus on 19p13.3 but also suggest the existence, in a minority of families, of a potential second PJS locus, on 19q13.4. Positional cloning and characterization of the PJS mutations will clarify the genetics of the syndrome and the implication of the gene(s) in the predisposition to neoplasias. PMID:9399902

  15. GpaXI ( tar ) ( l ) originating from Solanum tarijense is a major resistance locus to Globodera pallida and is localised on chromosome 11 of potato.

    PubMed

    Adillah Tan, M Y; Park, Tae-Ho; Alles, René; Hutten, Ronald C B; Visser, R G F; van Eck, Herman J

    2009-11-01

    Resistance to Globodera pallida Rookmaker (Pa3), originating from wild species Solanum tarijense was identified by QTL analysis and can be largely ascribed to one major QTL. GpaXI ( tar ) ( l ) explained 81.3% of the phenotypic variance in the disease test. GpaXI ( tar ) ( l ) is mapped to the long arm of chromosome 11. Another minor QTL explained 5.3% of the phenotypic variance and mapped to the long arm of chromosome 9. Clones containing both QTL showed no lower cyst counts than clones with only GpaXI ( tar ) ( l ) . After Mendelising the phenotypic data, GpaXI ( tar ) ( l ) could be more precisely mapped near markers GP163 and FEN427, thus anchoring GpaXI ( tar ) ( l ) to a region with a known R-gene cluster containing virus and nematode resistance genes. PMID:19816672

  16. 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

  17. 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

  18. 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

  19. Correlation of the Osteoarthritis Susceptibility Variants That Map to Chromosome 20q13 With an Expression Quantitative Trait Locus Operating on NCOA3 and With Functional Variation at the Polymorphism rs116855380

    PubMed Central

    Gee, Fiona; Rushton, Michael D.; Loughlin, John

    2015-01-01

    Objective To functionally characterize the osteoarthritis (OA) susceptibility variants that map to a region of high linkage disequilibrium (LD) on chromosome 20q13 marked by the single‐nucleotide polymorphism (SNP) rs6094710 and encompassing NCOA3 and SULF2. Methods Nucleic acids were extracted from the cartilage of OA patients. Overall and allelic expression of NCOA3 and SULF2 were measured by quantitative reverse transcription–polymerase chain reaction and pyrosequencing, respectively. The functional effect of SNPs within the 20q13 locus was assessed in vitro using luciferase reporter constructs and electrophoretic mobility shift assays (EMSAs). The in vivo effect of nuclear receptor coactivator 3 (NCOA3) protein depletion on primary human OA articular cartilage chondrocytes was assessed using RNA interference. Results Expression of NCOA3 correlated with the genotype at rs6094710 (P = 0.006), and the gene demonstrated allelic expression imbalance (AEI) in individuals heterozygous for the SNP (mean AEI 1.21; P < 0.0001). In both instances, expression of the OA‐associated allele was reduced. In addition, there was reduced enhancer activity of the OA‐associated allele of rs116855380, a SNP in perfect LD with rs6094710 in luciferase assays (P < 0.001). EMSAs demonstrated a protein complex binding with reduced affinity to this allele. Depletion of NCOA3 led to significant changes (all P < 0.05) in the expression of genes involved in cartilage homeostasis. Conclusion NCOA3 is subject to a cis‐acting expression quantitative trait locus in articular cartilage, which correlates with the OA association signal and with the OA‐associated allele of the functional SNP rs116855380, a SNP that is located only 10.3 kb upstream of NCOA3. These findings elucidate the effect of the association of the 20q13 region on OA cartilage and provide compelling evidence of a potentially causal candidate SNP. PMID:26211391

  20. 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.

  1. 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

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

    2016-04-01

    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 (A)γ-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 (A)γ-globin gene. Both hereditary persistence of fetal hemoglobin mutations result in a gain of (A)γ-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

  2. 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; Peterson, Kenneth R

    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

  3. 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

  4. 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.

  5. Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25

    PubMed Central

    Litchfield, Kevin; Sultana, Razvan; Renwick, Anthony; Dudakia, Darshna; Seal, Sheila; Ramsay, Emma; Powell, Silvana; Elliott, Anna; Warren-Perry, Margaret; Eeles, Rosalind; Peto, Julian; Kote-Jarai, Zsofia; Muir, Kenneth; Nsengimana, Jeremie; Stratton, Michael R.; Easton, Douglas F.; Bishop, D. Timothy; Huddart, Robert A.; Rahman, Nazneen; Turnbull, Clare; Pugh, J.; Linger, R.; Marke, J.; Hughes, D.; Pernet, D.; Hall, P.; Easton, D.F.; Berchuck, A.; Eeles, R.; Chenevix-Trench, G.; Dennis, J.; Dunning, A.M.; Lee, A.; Dicks, E.; Easton, D.F.; Benitez, J.; Gonzalez-Neira, A.; Simard, J.; Tessier, D.C.; Bacot, F.; Vincent, D.; LaBoissière, S.; Robidoux, F.; Bojesen, S.E.; Nielsen, S.F.; Nordestgaard, B.G.; Cunningham, J.M.; Windebank, S.A.; Hilker, C.A.; Meyer, J.

    2015-01-01

    Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06–1.27; P = 1.2 × 10−9]. PMID:25281660

  6. Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25.

    PubMed

    Litchfield, Kevin; Sultana, Razvan; Renwick, Anthony; Dudakia, Darshna; Seal, Sheila; Ramsay, Emma; Powell, Silvana; Elliott, Anna; Warren-Perry, Margaret; Eeles, Rosalind; Peto, Julian; Kote-Jarai, Zsofia; Muir, Kenneth; Nsengimana, Jeremie; Stratton, Michael R; Easton, Douglas F; Bishop, D Timothy; Huddart, Robert A; Rahman, Nazneen; Turnbull, Clare

    2015-02-15

    Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06-1.27; P = 1.2 × 10(-9)]. PMID:25281660

  7. 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

  8. Implication of a Chromosome 15q15.2 Locus in Regulating UBR1 and Predisposing Smokers to MGMT Methylation in Lung.

    PubMed

    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

    2015-08-01

    O(6)-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, 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

  9. 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

  10. Functional evaluation of the role of C-type lectin domain family 16A at the chromosome 16p13 locus

    PubMed Central

    Zouk, H; D'Hennezel, E; Du, X; Ounissi-Benkalha, H; Piccirillo, C A; Polychronakos, C

    2014-01-01

    The type 1 diabetes-associated 16p13 locus contains the CLEC16A gene. Its preferential immune cell expression suggests involvement in autoimmunity. Given its elevated expression in dendritic and B cells – known professional antigen-presenting cells (APCs) – we hypothesize that C-type lectin domain family 16 member A (CLEC16A) may be involved in T cell co-stimulation and consequent activation and proliferation. We also sought to identify CLEC16A's subcellular localization. The effect of the CLEC16A knock-down (KD) on B cell co-stimulation and activation of T cells was tested in human lymphoblastoid cell lines (LCLs) by co-culture with CD4+ T cells. T cell activation and proliferation were determined by flow-cytometric analysis of CD69 and CD25 expression and carboxyfluorescein succinimidyl ester (CFSE) dilution, respectively. CLEC16A subcellular localization in K562 cells was examined by immunofluorescence. We show that the CLEC16A KD did not affect the tested indices of lymphoblastoid cell line (LCL) APC capacity. Additionally, the percentage of activated T cells following LCL co-culture was not affected significantly by the CLEC16A KD. T cells co-cultured with KD or control LCLs also exhibited similar cell division profiles. CLEC16A co-localized with an endoplasmic reticulum (ER) marker, suggesting that it may be an ER protein. In conclusion, CLEC16A may not be involved in T cell co-stimulation. Additional studies on CLEC16A, accounting for its ER localization, are needed to uncover its biological role. PMID:24237155

  11. 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)

  12. 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.

  13. The inhibitor of wax 1 locus (Iw1) prevents formation of β- and OH-β-diketones in wheat cuticular waxes and maps to a sub-cM interval on chromosome arm 2BS.

    PubMed

    Adamski, Nikolai M; Bush, Maxwell S; Simmonds, James; Turner, Adrian S; Mugford, Sarah G; Jones, Alan; Findlay, Kim; Pedentchouk, Nikolai; von Wettstein-Knowles, Penny; Uauy, Cristobal

    2013-06-01

    Glaucousness is described as the scattering effect of visible light from wax deposited on the cuticle of plant aerial organs. In wheat, two dominant genes lead to non-glaucous phenotypes: Inhibitor of wax 1 (Iw1) and Iw2. The molecular mechanisms and the exact extent (beyond visual assessment) by which these genes affect the composition and quantity of cuticular wax is unclear. To describe the Iw1 locus we used a genetic approach with detailed biochemical characterization of wax compounds. Using synteny and a large number of F2 gametes, Iw1 was fine-mapped to a sub-cM genetic interval on wheat chromosome arm 2BS, which includes a single collinear gene from the corresponding Brachypodium and rice physical maps. The major components of flag leaf and peduncle cuticular waxes included primary alcohols, β-diketones and n-alkanes. Small amounts of C19-C27 alkyl and methylalkylresorcinols that have not previously been described in wheat waxes were identified. Using six pairs of BC2 F3 near-isogenic lines, we show that Iw1 inhibits the formation of β- and hydroxy-β-diketones in the peduncle and flag leaf blade cuticles. This inhibitory effect is independent of genetic background or tissue, and is accompanied by minor but consistent increases in n-alkanes and C24 primary alcohols. No differences were found in cuticle thickness and carbon isotope discrimination in near-isogenic lines differing at Iw1. PMID:23551421

  14. 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. PMID:26374166

  15. 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

  16. 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.

  17. 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

  18. Human ESP1/CRP2, a member of the LIM domain protein family: Characterization of the cDNA and assignment of the gene locus to chromosome 14q32.3

    SciTech Connect

    Karim, Mohammad Azharul; Ohta, Kohji; Matsuda, Ichiro

    1996-01-15

    The LIM domain is present in a wide variety of proteins with diverse functions and exhibits characteristic arrangements of Cys and His residues with a novel zinc-binding motif. LIM domain proteins have been implicated in development, cell regulation, and cell structure. A LIM domain protein was identified by screening a human cDNA library with rat cysteine-rich intestinal protein (CRIP) as a probe, under conditions of low stringency. Comparison of the predicted amino acid sequence with several LIM domain proteins revealed 93% of the residues to be identical to rat LIM domain protein, termed ESP1 or CRP2. Thus, the protein is hereafter referred to as human ESP1/CRP2. The cDNA encompasses a 1171-base region, including 26, 624, and 521 bases in the 5{prime}-noncoding region, coding region, and 3{prime}-noncoding regions, respectively, and encodes the entire ESP1/CRP2 protein has two LIM domains, and each shares 35.1% and 77 or 79% identical residues with human cysteine-rich protein (CRP) and rat CRIP, respectively. Northern blot analysis of ESP1/CRP2 in various human tissues showed distinct tissue distributions compared with CRP and CRIP, suggesting that each might serve related but specific roles in tissue organization or function. Using a panel of human-rodent somatic cell hybrids, the ESP1/CRP2 locus was assigned to chromosome 14. Fluorescence in situ hybridization, using cDNA and a genome DNA fragment of the ESP1/CRP2 as probes, confirms this assignment and relegates regional localization to band 14q32.3 47 refs., 7 figs.

  19. The CBFA2T3/ACSF3 locus is recurrently involved in IGH chromosomal translocation t(14;16)(q32;q24) in pediatric B-cell lymphoma with germinal center phenotype.

    PubMed

    Salaverria, Itziar; Akasaka, Takashi; Gesk, Stefan; Szczepanowski, Monika; Burkhardt, Birgit; Harder, Lana; Damm-Welk, Christine; Oschlies, Ilske; Klapper, Wolfram; Dyer, Martin J S; Siebert, Reiner

    2012-04-01

    Translocations involving immunoglobulin (IG) loci are the hallmarks of several subtypes of B-cell lymphoma. Common to these translocations is that cellular proto-oncogenes come under the influence of IG regulatory elements leading to deregulated expression. In case of a breakpoint in the IGH switch region, oncogene activation can take place on both derivative chromosomes, which means that in principle one translocation can result in concurrent activation of two genes. By fluorescence in situ hybridization (FISH), we identified a case of leukemic B-cell lymphoma in a child with an IGH break and unknown partner. Subsequent long-distance inverse PCR revealed fusion of IGH Sl in 14q32 and the 50 region of CBFA2T3 in 16q24.3, suggesting presence of the t(14;16)(q32;q24.3). Candidate oncogenes targeted through this translocation are CBFA2T3 and ACSF3, which could be activated on der(16) and der(14), respectively. FISH screening of a population-based cohort of B-cell lymphomas from a prospective trial for the treatment of lymphoma in childhood (BFM-NHL) identified additionally a follicular lymphoma Grade 3/diffuse large B-cell lymphoma with IGH-CBFA2T3/ACSF3 juxtaposition. Both lymphomas shared expression of CD10 and CD20 in the absence of TdT, suggesting a germinal center (GC) B-cell origin. Our data indicate that the CBFA2T3/ACSF3 locus is a novel recurrent oncogenic target of IGH translocations, which might contribute to the pathogenesis of pediatric GC-derived B-cell lymphoma. PMID:22420028

  20. 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.

  1. Quantitative trait locus analysis for hemostasis and thrombosis

    PubMed Central

    Sa, Qila; Hart, Erika; Hill, Annie E.; Nadeau, Joseph H.

    2009-01-01

    Susceptibility to thrombosis varies in human populations as well as many in inbred mouse strains. The objective of this study was to characterize the genetic control of thrombotic risk on three chromosomes. Previously, utilizing a tail-bleeding/rebleeding assay as a surrogate of hemostasis and thrombosis function, three mouse chromosome substitution strains (CSS) (B6-Chr5A/J, Chr11A/J, Chr17A/J) were identified (Hmtb1, Hmtb2, Hmtb3). The tailbleeding/rebleeding assay is widely used and distinguishes mice with genetic defects in blood clot formation or dissolution. In the present study, quantitative trait locus (QTL) analysis revealed a significant locus for rebleeding (clot stability) time (time between cessation of initial bleeding and start of the second bleeding) on chromosome 5, suggestive loci for bleeding time (time between start of bleeding and cessation of bleeding) also on chromosomes 5, and two suggestive loci for clot stability on chromosome 17 and one on chromosome 11. The three CSS and the parent A/J had elevated clot stability time. There was no interaction of genes on chromosome 11 with genes on chromosome 5 or chromosome 17. On chromosome 17, twenty-three candidate genes were identified in synteny with previously identified loci for thrombotic risk on human chromosome 18. Thus, we have identified new QTLs and candidate genes not previously known to influence thrombotic risk. PMID:18787898

  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. 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...

  4. Molecular characterization of a region of DNA associated with mutations at the agouti locus in the mouse.

    PubMed Central

    Bultman, S J; Russell, L B; Gutierrez-Espeleta, G A; Woychik, R P

    1991-01-01

    Molecular characterization of a radiation-induced agouti (a)-locus mutation has resulted in the isolation of a segment of DNA that maps at or near the a locus on chromosome 2 in the mouse. This region of DNA is deleted in several radiation- or chemical-induced homozygous-lethal a-locus mutations and is associated with specific DNA structural alterations in two viable a-locus mutations. We propose that DNA probes from this region of chromosome 2 will be useful for ultimately characterizing the individual gene or genes associated with a-locus function. Images PMID:1896452

  5. Spontaneous Formation of Compound X Chromosomes in Drosophila Melanogaster

    PubMed Central

    Morrison, R. J.; Raymond, J. D.; Zunt, J. R.; Lim, J. K.; Simmons, M. J.

    1988-01-01

    Males carrying different X chromosomes were tested for the ability to produce daughters with attached-X chromosomes. This ability is characteristic of males carrying an X chromosome derived from 59b-z, a multiply marked X chromosome, and is especially pronounced in males carrying the unstable 59b-z chromosomes Uc and Uc-l(r). Recombination experiments with one of the Uc-l(r) chromosomes showed that the formation of compound chromosomes depends on two widely separated segments. One of these is proximal to the forked locus and is probably proximal to the carnation locus. This segment may contain the actual site of chromosome attachment. The other essential segment lies between the crossveinless and vermilion loci and may contain multiple factors that influence the attachment process. PMID:3135238

  6. 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.

  7. 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. PMID:16845519

  8. Exclusion of epidermal growth factor and high-resolution physical mapping across the Rieger syndrome locus.

    PubMed Central

    Semina, E. V.; Datson, N. A.; Leysens, N. J.; Zabel, B. U.; Carey, J. C.; Bell, G. I.; Bitoun, P.; Lindgren, C.; Stevenson, T.; Frants, R. R.; van Ommen, G.; Murray, J. C.

    1996-01-01

    We have evaluated the 4q25-4q26 region where the autosomal dominant disorder Rieger syndrome has been previously mapped by linkage. We first excluded epidermal growth factor as a candidate gene by carrying out SSCP analysis of each of its 24 exons using a panel of seven unrelated individuals with Rieger syndrome. No evidence for etiologic mutations was detected in these individuals, although four polymorphic variants were identified, including three that resulted in amino acid changes. We next made use of two apparently balanced translocations, one familial and one sporadic, to identify a narrow physical localization likely to contain the gene or to be involved in regulation of gene function. Somatic cell hybrids were established from individuals with these balanced translocations, and these hybrids were used as a physical mapping resource for, first, preliminary mapping of the translocation breakpoints using known sequence tagged sites from chromosome 4 and then, after creating YAC and cosmids contigs encompassing the region, for fine mapping of those breakpoints. A cosmid contig spanning these breakpoints was identified and localized the gene to within approximately 150 kb of D4S193 on chromosome 4. The interval between the two independent translocations is approximately 50 kb in length and provides a powerful resource for gene identification. Images Figure 1 Figure 3 PMID:8940274

  9. A yeast artificial chromosome contig and NotI restriction map that spans the tumor suppressor gene(s) locus, 11q22.2-q23.3

    SciTech Connect

    Arai, Yasuhito; Hosoda, Fumie; Nakayama, Kyoko; Ohki, Misao

    1996-07-01

    Human chromosome 11q22-q23 is a pathologically important region in which a high level of loss of heterozygosity has been reported for breast, ovary, cervical, colon, and lung carcinomas, malignant melanomas, and hematologic malignancies. This strongly indicates that one or more tumor suppressor genes reside within the deleted region. In this report, we report the development of a contig map that covers most of the deleted regions found in these malignancies. The map comprises a contig of 66 overlapping yeast artificial chromosomes (YACs) and spans a region of 17 Mb from the PGR gene at 11q22.2 to the MLL gene at q23.3. In the process of screening the YACs, 50 new sequence-tagged site markers were developed from the termini of the YAC inserts. These markers were used for chromosome walking, and the data were then integrated into the contig map. NotI sites in the region. Using 22 of them, a NotI restriction map of the region from PGR to D11S939 was developed. This YAC contig will provide efficient tools for identification of the putative tumor suppressor gene(s). 49 refs., 3 figs., 2 tabs.

  10. Cloning of the gene encoding the. delta. subunit of the human T-cell receptor reveals its physical organization within the. alpha. -subunit locus and its involvement in chromosome translocations in T-cell malignancy

    SciTech Connect

    Isobe, M.; Russo, G.; Haluska, F.G.; Croce, C.M. )

    1988-06-01

    By taking advantage of chromosomal walking techniques, the authors have obtained clones that encompass the T-cell receptor (TCR) {delta}-chain gene. They analyzed clones spanning the entire J{sub {alpha}} region extending 115 kilobases 5{prime} of the TCR {alpha}-chain constant region and have shown that the TCR {delta}-chain gene is located over 80 kilobases 5{prime} of C{sub {alpha}}. TCR {delta}-chain gene is rearranged in the {gamma}/{delta}-expressing T-cell line Peer and is deleted in {alpha}/{beta}-expressing T-cell lines. Sequence analysis of portions of this genomic region demonstrates its identity with previously described cDNA clones corresponding to the C{sub {delta}} and J{sub {delta}} segments. Furthermore, they have analyzed a t(8;14)-(q24;q11) chromosome translocation from a T-cell leukemia and have shown that the J{sub {delta}} segment is rearranged in cells deriving from this tumor and probably directly involved in the translocation. Thus, the newly clones TCR {delta} chain is implicated in the genesis of chromosome translocations in T-cell malignancies carrying cytogenetic abnormalities of band 14q11.

  11. Structure of the Catfish IGH Locus: Analysis of the Region Including the Single Functional IGHM Gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The catfish IGH locus is large (~1Mb) and complex, having undergone multiple internal duplications and transpositions. To define the structure of the locus that contains the single expressed IGHM gene, two overlapping bacterial-artificial-chromosome (BAC) clones spanning the most 3’ end of the chann...

  12. 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. PMID:18493797

  13. Cloning of the human dopamine D5 receptor gene and identification of a highly polymorphic microsatellite for the DRD5 locus that shows tight linkage to the chromosome 4p reference marker RAF1P1

    SciTech Connect

    Sherrington, R.; Mankoo, B.; Kalsi, G.; Gurling, H.; Curtis, D. ); Attwood, J.; Povey, S. ); Buetow, K. )

    1993-11-01

    The authors identified a cosmid clone with exact sequence homology to part of the human dopamine D5 receptor gene (DRD5) after screening a cosmid library with the human DRD1 gene. The dopamine D5 receptor was mapped to chromosome 4p15.1-p15.3 by in situ hybridization and using a somatic cell hybrid panel. They report here the further localization of the DRD5 gene following identification of a highly polymorphic dinucleotide repeat sequence in the cosmid clone. The microsatellite (D5(CT/GT/GA)[sub n]) had 12 alleles with a polymorphic information content value of 0.77. Linkage analysis in 39 CEPH pedigrees demonstrated tight linkage to the chromosome 4p reference marker RAF1P1 (Z[sub maxf] 20.66 at [theta][sub f] 0.05 and Z[sub maxM] 16.57 at [theta][sub m] 0.07). 16 refs., 2 tabs.

  14. A chromosome 11 YAC library

    SciTech Connect

    Qin, S.; Zhang, J.; Isaacs, C.M.; Nagafuchi, S.; Jani Sait, S.N.; Abel, K.J.; Higgins, M.J.; Nowak, N.J.; Shows, T.B. )

    1993-06-01

    A targeted yeast artificial chromosome (YAC) library for chromosome 11 has been constructed from the J1 cell line that carries a single human chromosome 11 within a hamster DNA background. Interspecies chimeric clones generated during construction of the library were detected during the screening process and eliminated from the library. Contig assembly becomes much less difficult using such a library as the complexity is decreased and the ends of the clone inserts can be rescued for walking to neighboring clones. The library contains > 1824 clones with an average insert length of 337 kb. This represents a fourfold coverage of chromosome 11 or a >95% chance of recovering a unique single-copy sequence from the library. Two hundred YAC clones were localized by fluorescence in situ hybridization and found to be randomly distributed along the chromosome. The library has been screened with probes for the chromosome 11 markers HBB, GLUR4, H19, and D11S193. Corresponding YAC clones have been isolated for each locus. This analysis has indicated that the library is unbiased, that cognate YAC clones can be recovered with chromosome 11 markers, and that extensive contig assembly should be feasible. 31 refs., 5 figs.

  15. 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.

  16. 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.

  17. 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.

  18. 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…

  19. Two forms of loops generate the chromatin conformation of the immunoglobulin heavy chain gene locus

    PubMed Central

    Guo, Changying; Gerasimova, Tatiana; Hao, Haiping; Ivanova, Irina; Chakraborty, Tirtha; Selimyan, Roza; Oltz, Eugene M.; Sen, Ranjan

    2013-01-01

    SUMMARY The immunoglobulin heavy chain (IgH) gene locus undergoes radial re-positioning within the nucleus and locus contraction in preparation for gene recombination. We demonstrate that IgH locus conformation involves two levels of chromosomal compaction. At the first level the locus folds into several multi-looped domains. One such domain at the 3′ end of the locus requires an enhancer, Eμ; two other domains at the 5′ end are Eμ-independent. At the second level, these domains are brought into spatial proximity by Eμ-dependent interactions with specific sites within the VH region. Eμ is also required for radial re-positioning of IgH alleles indicating its essential role in large scale chromosomal movements in developing lymphocytes. Our observations provide a comprehensive view of the conformation of IgH alleles in pro-B cells and the mechanisms by which it is established. PMID:21982154

  20. 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.

  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. Characterization of a recombination event excluding the Harvey-ras-1 (H-ras-1) locus in a Ramano-Ward Long QT syndrome family linked to Chromosome 11q15 and isolation of a polymorphic repeat telomeric to H-ras-1

    SciTech Connect

    Russell, M.W.; Brody, L.C.; Munroe, D.

    1994-09-01

    The Romano-Ward Long QT syndrome (RWLQTS) has been linked to 11p15.5 in several large families but demonstrates genetic heterogeneity, since in other families the RWLQTS phenotype is not linked to 11p15. To date, no recombinants between the H-Ras-1 locus and RWLQTS in families linked to 11p15 have been published. In a large family, we demonstrate linkage of RWLQTS to marker D11S932 on chromosome 11p15.4 with a LOD score of 3.14 ({theta}=0;90% penetrance). An unaffected individual and her two unaffected offspring inherited the affected haplotype for the H-ras-1 region telomeric to D11S932. All three have QTc measurements of {le} 0.40 seconds and no history of syncope, making the diagnosis of RWLQTS extremely unlikely. This suggests that, although the gene for the RWlQTS is linked to 11p15 in this family, a recombination event may have occurred that separated the RWLQTS gene from the affected H-ras-1 region haplotype. To investigate a possible telomeric recombination event, cosmids telomeric to H-ras-1 were isolated. A highly polymorphic, complex CA/CT repeat marker (78% heterozygosity) was characterized and its location telomeric to H-ras-1 verified by interphase FISH. The same three unaffected individuals had the affected allele for this marker, ruling our recombination telomeric to H-ras-1 but proximal to the new marker. As the most telemeric marker on 11p to date, this marker will aid the physical and genetic mapping of the 11p telomere. The potential recombination event in this family apparently excludes H-ras-1 as a candidate gene and may aid the localization of the RWLQTS gene linked to 11p15.5. However, it remains a possibility that another genetic locus on 11p15, in addition to the one near the H-ras-1 gene, can cause the RWLQTS phenotype. This is the first report of recombination between H-ras-1 and RWLQTS in a family linked to 11p15.

  3. 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.

  4. 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 ...

  5. Donor Locus Selection during Saccharomyces Cerevisiae Mating Type Interconversion Responds to Distant Regulatory Signals

    PubMed Central

    Weiler, K. S.; Broach, J. R.

    1992-01-01

    Mating type interconversion in homothallic strains of the yeast Saccharomyces cerevisiae results from directed transposition of a mating type allele from one of the two silent donor loci, HML and HMR, to the expressing locus, MAT. Cell type regulates the selection of the particular donor locus to be utilized during mating type interconversion: MATa cells preferentially select HMLα and MATα cells preferentially select HMRa. Such preferential selection indicates that the cell is able to distinguish between HML and HMR during mating type interconversion. Accordingly, we designed experiments to identify those features perceived by the cell to discriminate HML and HMR. We demonstrate that discrimination does not derive from the different structures of the HML and HMR loci, from the unique sequences flanking each donor locus nor from any of the DNA distal to the HM loci on chromosome III. Moreover, we find that the sequences flanking the MAT locus do not function in the preferential selection of one donor locus over the other. We propose that the positions of the donor loci on the left and right arms of chromosome III is the characteristic utilized by the cell to distinguish HML and HMR. This positional information is not generated by either CEN3 or the MAT locus, but probably derives from differences in the chromatin structure, chromosome folding or intranuclear localization of the two ends of chromosome III. PMID:1459444

  6. 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

  7. 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. PMID:9090054

  8. Synthetic chromosomes.

    PubMed

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes. PMID:26111960

  9. 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.

  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. 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

  12. Recombination Suppression by Heterozygous Robertsonian Chromosomes in the Mouse

    PubMed Central

    Davisson, M. T.; Akeson, E. C.

    1993-01-01

    Robertsonian chromosomes are metacentric chromosomes formed by the joining of two telocentric chromosomes at their centromere ends. Many Robertsonian chromosomes of the mouse suppress genetic recombination near the centromere when heterozygous. We have analyzed genetic recombination and meiotic pairing in mice heterozygous for Robertsonian chromosomes and genetic markers to determine (1) the reason for this recombination suppression and (2) whether there are any consistent rules to predict which Robertsonian chromosomes will suppress recombination. Meiotic pairing was analyzed using synaptonemal complex preparations. Our data provide evidence that the underlying mechanism of recombination suppression is mechanical interference in meiotic pairing between Robertsonian chromosomes and their telocentric partners. The fact that recombination suppression is specific to individual Robertsonian chromosomes suggests that the pairing delay is caused by minor structural differences between the Robertsonian chromosomes and their telocentric homologs and that these differences arise during Robertsonian formation. Further understanding of this pairing delay is important for mouse mapping studies. In 10 mouse chromosomes (3, 4, 5, 6, 8, 9, 10, 11, 15 and 19) the distances from the centromeres to first markers may still be underestimated because they have been determined using only Robertsonian chromosomes. Our control linkage studies using C-band (heterochromatin) markers for the centromeric region provide improved estimates for the centromere-to-first-locus distance in mouse chromosomes 1, 2 and 16. PMID:8454207

  13. Evidence for a third genetic locus for autosomal dominant polycystic kidney disease

    SciTech Connect

    Daoust, M.C.; Bichet, D.G.; Reynolds, D.M.

    1995-02-10

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disease with loci on chromosomes 16p and 4q. It has a moderately high spontaneous mutation rate, although the relative frequency of such mutations at each gene locus is unknown. In studying genetic heterogeneity in the French-Canadian population, we identified a family in which a classical clinical presentation of ADPKD resulted from a mutation at a locus genetically distinct from either of the previously described loci for this disease. This suggests the existence of a third genetic locus for ADPKD. 21 refs., 1 fig., 1 tab.

  14. 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

  15. 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.

  16. Identifying a novel locus for psoriatic arthritis.

    PubMed

    Budu-Aggrey, Ashley; Bowes, John; Barton, Anne

    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

  17. 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

  18. Organization of the cpe Locus in CPE-Positive Clostridium perfringens Type C and D Isolates

    PubMed Central

    Li, Jihong; Miyamoto, Kazuaki; Sayeed, Sameera; McClane, Bruce A.

    2010-01-01

    Clostridium perfringens enterotoxin (encoded by the cpe gene) contributes to several important human, and possibly veterinary, enteric diseases. The current study investigated whether cpe locus organization in type C or D isolates resembles one of the three (one chromosomal and two plasmid-borne) cpe loci commonly found amongst type A isolates. Multiplex PCR assays capable of detecting sequences in those type A cpe loci failed to amplify products from cpe-positive type C and D isolates, indicating these isolates possess different cpe locus arrangements. Therefore, restriction fragments containing the cpe gene were cloned and sequenced from two type C isolates and one type D isolate. The obtained cpe locus sequences were then used to construct an overlapping PCR assay to assess cpe locus diversity amongst other cpe-positive type C and D isolates. All seven surveyed cpe-positive type C isolates had a plasmid-borne cpe locus partially resembling the cpe locus of type A isolates carrying a chromosomal cpe gene. In contrast, all eight type D isolates shared the same plasmid-borne cpe locus, which differed substantially from the cpe locus present in other C. perfringens by containing two copies of an ORF with 67% identity to a transposase gene (COG4644) found in Tn1546, but not previously associated with the cpe gene. These results identify greater diversity amongst cpe locus organization than previously appreciated, providing new insights into cpe locus evolution. Finally, evidence for cpe gene mobilization was found for both type C and D isolates, which could explain their cpe plasmid diversity. PMID:20532170

  19. 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

  20. 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

  1. The DNA sequence and analysis of human chromosome 13

    PubMed Central

    Dunham, A.; Matthews, L. H.; Burton, J.; Ashurst, J. L.; Howe, K. L.; Ashcroft, K. J.; Beare, D. M.; Burford, D. C.; Hunt, S. E.; Griffiths-Jones, S.; Jones, M. C.; Keenan, S. J.; Oliver, K.; Scott, C. E.; Ainscough, R.; Almeida, J. P.; Ambrose, K. D.; Andrews, D. T.; Ashwell, R. I. S.; Babbage, A. K.; Bagguley, C. L.; Bailey, J.; Bannerjee, R.; Barlow, K. F.; Bates, K.; Beasley, H.; Bird, C. P.; Bray-Allen, S.; Brown, A. J.; Brown, J. Y.; Burrill, W.; Carder, C.; Carter, N. P.; Chapman, J. C.; Clamp, M. E.; Clark, S. Y.; Clarke, G.; Clee, C. M.; Clegg, S. C. M.; Cobley, V.; Collins, J. E.; Corby, N.; Coville, G. J.; Deloukas, P.; Dhami, P.; Dunham, I.; Dunn, M.; Earthrowl, M. E.; Ellington, A. G.; Faulkner, L.; Frankish, A. G.; Frankland, J.; French, L.; Garner, P.; Garnett, J.; Gilbert, J. G. R.; Gilson, C. J.; Ghori, J.; Grafham, D. V.; Gribble, S. M.; Griffiths, C.; Hall, R. E.; Hammond, S.; Harley, J. L.; Hart, E. A.; Heath, P. D.; Howden, P. J.; Huckle, E. J.; Hunt, P. J.; Hunt, A. R.; Johnson, C.; Johnson, D.; Kay, M.; Kimberley, A. M.; King, A.; Laird, G. K.; Langford, C. J.; Lawlor, S.; Leongamornlert, D. A.; Lloyd, D. M.; Lloyd, C.; Loveland, J. E.; Lovell, J.; Martin, S.; Mashreghi-Mohammadi, M.; McLaren, S. J.; McMurray, A.; Milne, S.; Moore, M. J. F.; Nickerson, T.; Palmer, S. A.; Pearce, A. V.; Peck, A. I.; Pelan, S.; Phillimore, B.; Porter, K. M.; Rice, C. M.; Searle, S.; Sehra, H. K.; Shownkeen, R.; Skuce, C. D.; Smith, M.; Steward, C. A.; Sycamore, N.; Tester, J.; Thomas, D. W.; Tracey, A.; Tromans, A.; Tubby, B.; Wall, M.; Wallis, J. M.; West, A. P.; Whitehead, S. L.; Willey, D. L.; Wilming, L.; Wray, P. W.; Wright, M. W.; Young, L.; Coulson, A.; Durbin, R.; Hubbard, T.; Sulston, J. E.; Beck, S.; Bentley, D. R.; Rogers, J.; Ross, M. T.

    2009-01-01

    Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb. PMID:15057823

  2. The DNA sequence and analysis of human chromosome 13.

    PubMed

    Dunham, A; Matthews, L H; Burton, J; Ashurst, J L; Howe, K L; Ashcroft, K J; Beare, D M; Burford, D C; Hunt, S E; Griffiths-Jones, S; Jones, M C; Keenan, S J; Oliver, K; Scott, C E; Ainscough, R; Almeida, J P; Ambrose, K D; Andrews, D T; Ashwell, R I S; Babbage, A K; Bagguley, C L; Bailey, J; Bannerjee, R; Barlow, K F; Bates, K; Beasley, H; Bird, C P; Bray-Allen, S; Brown, A J; Brown, J Y; Burrill, W; Carder, C; Carter, N P; Chapman, J C; Clamp, M E; Clark, S Y; Clarke, G; Clee, C M; Clegg, S C M; Cobley, V; Collins, J E; Corby, N; Coville, G J; Deloukas, P; Dhami, P; Dunham, I; Dunn, M; Earthrowl, M E; Ellington, A G; Faulkner, L; Frankish, A G; Frankland, J; French, L; Garner, P; Garnett, J; Gilbert, J G R; Gilson, C J; Ghori, J; Grafham, D V; Gribble, S M; Griffiths, C; Hall, R E; Hammond, S; Harley, J L; Hart, E A; Heath, P D; Howden, P J; Huckle, E J; Hunt, P J; Hunt, A R; Johnson, C; Johnson, D; Kay, M; Kimberley, A M; King, A; Laird, G K; Langford, C J; Lawlor, S; Leongamornlert, D A; Lloyd, D M; Lloyd, C; Loveland, J E; Lovell, J; Martin, S; Mashreghi-Mohammadi, M; McLaren, S J; McMurray, A; Milne, S; Moore, M J F; Nickerson, T; Palmer, S A; Pearce, A V; Peck, A I; Pelan, S; Phillimore, B; Porter, K M; Rice, C M; Searle, S; Sehra, H K; Shownkeen, R; Skuce, C D; Smith, M; Steward, C A; Sycamore, N; Tester, J; Thomas, D W; Tracey, A; Tromans, A; Tubby, B; Wall, M; Wallis, J M; West, A P; Whitehead, S L; Willey, D L; Wilming, L; Wray, P W; Wright, M W; Young, L; Coulson, A; Durbin, R; Hubbard, T; Sulston, J E; Beck, S; Bentley, D R; Rogers, J; Ross, M T

    2004-04-01

    Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb. PMID:15057823

  3. 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.

  4. Deficient transcription of XIST from tiny ring X chromosomes in females with severe phenotypes.

    PubMed Central

    Migeon, B R; Luo, S; Stasiowski, B A; Jani, M; Axelman, J; Van Dyke, D L; Weiss, L; Jacobs, P A; Yang-Feng, T L; Wiley, J E

    1993-01-01

    The severe phenotype of human females whose karyotype includes tiny ring X chromosomes has been attributed to the inability of the small ring X chromosome to inactivate. The XIST locus is expressed only from the inactive X chromosome, resides at the putative X inactivation center, and is considered a prime player in the initiation of mammalian X dosage compensation. Using PCR, Southern blot analysis, and in situ hybridization, we have looked for the presence of the XIST locus in tiny ring X chromosomes from eight females who have multiple congenital malformations and severe mental retardation. Our studies reveal heterogeneity within this group; some rings lack the XIST locus, while others have sequences homologous to probes for XIST. However, in the latter, the locus is either not expressed or negligibly expressed, based on reverse transcription-PCR analysis. Therefore, what these tiny ring chromosomes have in common is a level of XIST transcription comparable to an active X. As XIST transcription is an indicator of X chromosome inactivity, the absence of XIST transcription strongly suggests that tiny ring X chromosomes in females with severe phenotypes are mutants in the X chromosome inactivation pathway and that the inability of these rings to inactivate is responsible for the severe phenotypes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8265665

  5. 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.

  6. 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.

  7. Dynamics of R1 and R2 elements in the rDNA locus of Drosophila simulans.

    PubMed Central

    Pérez-González, C E; Eickbush, T H

    2001-01-01

    The mobile elements R1 and R2 insert specifically into the rRNA gene locus (rDNA locus) of arthropods, a locus known to undergo concerted evolution, the recombinational processes that preserve the sequence homogeneity of all repeats. To monitor how rapidly individual R1 and R2 insertions are turned over in the rDNA locus by these processes, we have taken advantage of the many 5' truncation variants that are generated during the target-primed reverse transcription mechanism used by these non-LTR retrotransposons for their integration. A simple PCR assay was designed to reveal the pattern of the 5' variants present in the rDNA loci of individual X chromosomes in a population of Drosophila simulans. Each rDNA locus in this population was found to have a large, unique collection of 5' variants. Each variant was present at low copy number, usually one copy per chromosome, and was seldom distributed to other chromosomes in the population. The failure of these variants to spread to other units in the same rDNA locus suggests a strong recombinational bias against R1 and R2 that results in the individual copies of these elements being rapidly lost from the rDNA locus. This bias suggests a significantly higher frequency of R1 and R2 retrotransposition than we have previously suggested. PMID:11514447

  8. Thorough investigation of a canine autoinflammatory disease (AID) confirms one main risk locus and suggests a modifier locus for amyloidosis.

    PubMed

    Olsson, Mia; Tintle, Linda; Kierczak, Marcin; Perloski, Michele; Tonomura, Noriko; Lundquist, Andrew; Murén, Eva; Fels, Max; Tengvall, Katarina; Pielberg, Gerli; Dufaure de Citres, Caroline; Dorso, Laetitia; Abadie, Jérôme; Hanson, Jeanette; Thomas, Anne; Leegwater, Peter; Hedhammar, Åke; Lindblad-Toh, Kerstin; Meadows, Jennifer R S

    2013-01-01

    Autoinflammatory disease (AID) manifests from the dysregulation of the innate immune system and is characterised by systemic and persistent inflammation. Clinical heterogeneity leads to patients presenting with one or a spectrum of phenotypic signs, leading to difficult diagnoses in the absence of a clear genetic cause. We used separate genome-wide SNP analyses to investigate five signs of AID (recurrent fever, arthritis, breed specific secondary dermatitis, otitis and systemic reactive amyloidosis) in a canine comparative model, the pure bred Chinese Shar-Pei. Analysis of 255 DNA samples revealed a shared locus on chromosome 13 spanning two peaks of association. A three-marker haplotype based on the most significant SNP (p<2.6×10(-8)) from each analysis showed that one haplotypic pair (H13-11) was present in the majority of AID individuals, implicating this as a shared risk factor for all phenotypes. We also noted that a genetic signature (F ST) distinguishing the phenotypic extremes of the breed specific Chinese Shar-Pei thick and wrinkled skin, flanked the chromosome 13 AID locus; suggesting that breed development and differentiation has played a parallel role in the genetics of breed fitness. Intriguingly, a potential modifier locus for amyloidosis was revealed on chromosome 14, and an investigation of candidate genes from both this and the chromosome 13 regions revealed significant (p<0.05) renal differential expression in four genes previously implicated in kidney or immune health (AOAH, ELMO1, HAS2 and IL6). These results illustrate that phenotypic heterogeneity need not be a reflection of genetic heterogeneity, and that genetic modifiers of disease could be masked if syndromes were not first considered as individual clinical signs and then as a sum of their component parts. PMID:24130694

  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. Measuring chromosome conformation with degenerate labels

    NASA Astrophysics Data System (ADS)

    Ross, Brian C.; Wiggins, Paul A.

    2012-07-01

    Although DNA conformation plays an integral role in all genetic processes from transcription to chromosome segregation, there is as yet no tractable method for capturing the in vivo conformation of a chromosome at high resolution. Labeling and fluorescently imaging thousands of loci along the chromosome would readily yield a conformation if each locus could be uniquely distinguished in the image, but this would unrealistically require thousands of distinguishable labels and a tedious experimental process. Here we present a computational method for extracting conformations when the total number of labels far exceeds the number of distinguishable labels. We evaluate our technique using simulated conformations with lengths ranging from 10 to 100 kilobases, and discuss the prospects for an experiment.

  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. 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.

  13. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence on X chromosome inactivation.

    PubMed Central

    Bu, X D; Rotter, J I

    1991-01-01

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, we show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, we have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11 +/- 0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus. PMID:1896469

  14. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: Evidence from segregation analysis for dependence on X chromosome inactivation

    SciTech Connect

    Xiangdong Bu; Rotter, J.I. Univ. of California, Los Angeles )

    1991-09-15

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, the authors show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, they have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11{plus minus}0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.l08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.

  15. 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

  16. Escape from Genomic Imprinting at the Mouse T-Associated Maternal Effect (Tme) Locus

    PubMed Central

    Tsai, J. Y.; Silver, L. M.

    1991-01-01

    Genomic imprinting occurs at the paternally inherited allele of the mouse T-associated maternal effect (Tme) locus. As a consequence, maternal transmission of a functional Tme gene is normally required for viability and individuals that receive a Tme-deleted chromosome (T(hp) or t(lub2)) from their mother die late in gestation or shortly thereafter. Here we report that a rearranged paternally derived chromosome duplicated for the Tme locus can act to rescue animals that have not received a maternal copy of the Tme locus. Unexpectedly, all rescued animals display an abnormal short/kinky tail phenotype. Somatic transfer of genomic imprinting between homologs by means of a transvection-like process between paired Tme and T loci is proposed as a model to explain the results obtained. PMID:1783296

  17. Positional cloning of the major quantitative trait locus underlying lung tumor susceptibility in mice

    PubMed Central

    Zhang, Zhongqiu; Futamura, Manabu; Vikis, Haris G.; Wang, Min; Li, Jie; Wang, Yian; Guan, Kun-Liang; You, Ming

    2003-01-01

    Pulmonary adenoma susceptibility 1 (Pas1), located on chromosome 6, is the major locus affecting inherited predisposition to lung tumor development in mice. We have fine mapped the Pas1 locus to a region of ≈0.5 megabases by using congenic strains of mice, constructed by placing the Pas1 region of chromosome 6 from A/J mice onto the genetic background of C57BL/6J mice. Systematic characterization of Pas1 candidates establishes the Las1 (lung adenoma susceptibility 1) and Kras2 (Kirsten rat sarcoma oncogene 2) genes as primary candidates for the Pas1 locus. Clearly, Kras2 affects lung tumor progression only, and Las1 is likely to affect lung tumor multiplicity. PMID:14583591

  18. Mapping studies of Hirschsprung disease on chromosome 13q22

    SciTech Connect

    Puffenberger, E.G.; Washington, S.S.; Cass, D.

    1994-09-01

    We have identified a large, inbred, Mennonite kindred segregating HSCR. An association mapping study was initiated to identify the gene(s) involved in the development of HSCR. Presuming segregation of a recessive locus, we searched the genome at low resolution with three multi-case families for chromosomal regions demonstrating identity-by-descent (IBD). Regions demonstrating IBD in all three mapping panel families were analyzed at high resolution using 31 additional nuclear families. This method identified a major susceptibility locus on chromosome 13q22. Four microsatellite markers, viz. D13S162, D13S160, AFM240zg9, and D13S170, showed significant results (p<0.001) when the frequency of alleles at each locus was compared between transmitted (T) and untransmitted (U) parental alleles. An additional marker, D13S317, has since been genotyped and found to demonstrate significant linkage disequilibrium as well. At locus D13S160, the 235 bp allele shows the strongest association. To estimate the penetrance of the mutant gene on 13q22, we genotyped all 58 offspring in 14 segregating (for D13S160) nuclear families. This analysis demonstrated that 36% (8/22) of 235 bp homozygotes and 27% (7/26) of 235 bp heterozygotes we affected. Overall, the calculated penetrance is 31% which accords well with the 33% value estimated by Badner et al. (1990) for colonic HSCR. In addition, two patients with HSCR and interstitial deletions of chromosome 13 have been analyzed with microsatellite markers. The common overlap region includes l3q22 and is bounded distally by D13S160. This region is thought to be syntenic with mouse chromosome 14 where the piebald locus maps. While the piebald locus is recessive and the 13q22 deletion patients argue for dominant inheritance, the mapping data from the Mennonite kindred favors an intermediate model where homozygotes are at greatest risk, but heterozygotes have a measurable risk for HSCR development.

  19. Silver-Russell syndrome without body asymmetry in three patients with duplications of maternally derived chromosome 11p15 involving CDKN1C.

    PubMed

    Nakashima, Shinichi; Kato, Fumiko; Kosho, Tomoki; Nagasaki, Keisuke; Kikuchi, Toru; Kagami, Masayo; Fukami, Maki; Ogata, Tsutomu

    2015-02-01

    We report duplications of maternally derived chromosome 11p15 involving CDKN1C encoding a negative regulator for cell proliferation in three Japanese patients (cases 1 and 2 from family A and case 3 from family B) with Silver-Russell syndrome (SRS) phenotype lacking hemihypotrophy. Chromosome analysis showed 46,XX,der(16)t(11;16)(p15.3;q24.3)mat in case 1, 46,XY,der(16)t(11;16)(p15.3;q24.3)mat in case 2 and a de novo 46,XX,der(17)t(11;17)(p15.4;q25.3) in case 3. Genomewide oligonucleotide-based array comparative genomic hybridization, microsatellite analysis, pyrosequencing-based methylation analysis and direct sequence analysis revealed the presence of maternally derived extra copies of the distal chromosome 11p involving the wild-type CDKN1C (a ~7.98 Mb region in cases 1 and 2 and a ~4.43 Mb region in case 3). The results, in conjunction with the previous findings in patients with similar duplications encompassing CDKN1C and in those with intragenic mutations of CDKN1C, imply that duplications of CDKN1C, as well as relatively mild gain-of-function mutations of CDKN1C lead to SRS subtype that usually lack hemihypotrophy. PMID:25427884

  20. Ink4-Arf locus in cancer and aging.

    PubMed

    Sherr, Charles J

    2012-01-01

    Three tumor suppressor genes at the small (<50 kb) INK4-ARF (CDKN2A/B) locus on human chromosome 9p21 coordinate a signaling network that depends on the activities of the retinoblastoma (RB) protein and the p53 transcription factor. Disruption of this circuitry, frequently by codeletion of INK4-ARF, is a hallmark of cancer, begging the question of why the intimate genetic linkage of these tumor suppressor genes has been maintained in mammals despite the risk of their coinactivation. The INK4-ARF locus is not highly expressed under normal physiologic conditions in young mammals, but its induction becomes more pronounced as animals age. Notably, INK4-ARF is actively silenced en bloc in embryonic, fetal, and adult stem cells but becomes poised to respond to oncogenic stress signals as stem cells lose their self-renewal capacity and differentiate, thereby providing a potent barrier to tumor formation. Epigenetic remodeling of the locus as a whole provides a mechanism for coordinating the activities of RB and p53. A hypothesis is that the INK4-ARF locus may have evolved to physiologically restrict the self-renewal capacities and numbers of stem and progenitor cells with the attendant consequence of limiting tissue regenerative capacity, particularly as animals age. Deletion of INK4-ARF contributes to the aberrant self-renewal capacity of tumor cells and occurs frequently in many forms of human cancer. PMID:22960768

  1. 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.

  2. 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...

  3. Cross-species identification of Mendel's I locus.

    PubMed

    Armstead, Ian; Donnison, Iain; Aubry, Sylvain; Harper, John; Hörtensteiner, Stefan; James, Caron; Mani, Jan; Moffet, Matt; Ougham, Helen; Roberts, Luned; Thomas, Ann; Weeden, Norman; Thomas, Howard; King, Ian

    2007-01-01

    A key gene involved in plant senescence, mutations of which partially disable chlorophyll catabolism and confer stay-green leaf and cotyledon phenotypes, has been identified in Pisum sativum, Arabidopsis thaliana, and Festuca pratensis by using classical and molecular genetics and comparative genomics. A stay-green locus in F. pratensis is syntenically equivalent to a similar stay-green locus on rice chromosome 9. Functional testing in Arabidopsis of a homolog of the rice candidate gene revealed (i) senescence-associated gene expression and (ii) a stay-green phenotype after RNA interference silencing. Genetic mapping in pea demonstrated cosegregation with the yellow/green cotyledon polymorphism (I/i) first reported by Gregor Mendel in 1866. PMID:17204643

  4. The mouse lysosomal membrane protein 1 gene as a candidate for the motorneuron degeneration (mnd) locus

    SciTech Connect

    Bermingham, N.A.; Martin, J.E.; Fisher, E.M.C.

    1996-03-01

    The motorneuron degeneration (mnd) mutation causes one of the few late-onset progressive neurodegenerations in mice; therefore, the mnd mouse is a valuable paradigm for studying neurodegenerative biology. The mnd mutation may also model human neuronal ceroid lipofuscinosis (NCL) or Batten disease. Mnd maps to the centromeric region of mouse chromosome 8, which likely corresponds to portions of human chromosomes 13,8, or 19; we note that the chromosome 13 portion maps close to a region thought to contain the human Type V NCL locus. We have identified candidate genes for the mnd locus from human chromosomes 13, 8, and 19, and we are mapping these genes in the mouse to determine their proximity to the mutated locus and to refine the comparative human-mouse map in this area. A candidate gene from human chromosome 13 is LAMP1, which encodes lysosomal membrane protein 1. We found that Lamp1 in the mouse lies within the region of the mnd mutation. Therefore, we sequenced Lamp1 cDNAs from homozygous mnd mice and unrelated wildtype C57BL/6 mice. We find no differences between the two cDNA species in the regions examined, and expression analysis shows a similar LAMP1 protein distribution in wildtype and mutant mice, suggesting that an abnormal accumulation of material within normal lysosome structures is unlikely to be the pathogenetic mechanism in the mnd mouse. 19 refs., 3 figs.

  5. A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens.

    PubMed Central

    McDaniel, T K; Jarvis, K G; Donnenberg, M S; Kaper, J B

    1995-01-01

    Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli O157:H7 are intestinal pathogens that profoundly damage the microvilli and subapical cytoskeleton of epithelial cells. Here we report finding in EPEC a 35-kbp locus containing several regions implicated in formation of these lesions. DNA probes throughout this locus hybridize to E. coli O157:H7 and other pathogens of three genera that cause similar lesions but do not hybridize to avirulent members of the same species. The EPEC locus and a different virulence locus of uropathogenic E. coli insert into the E. coli chromosome at the identical site and share highly similar sequences near the point of insertion. Images Fig. 1 Fig. 3 PMID:7878036

  6. Evidence for a fourth locus in Usher syndrome type I.

    PubMed Central

    Gerber, S; Larget-Piet, D; Rozet, J M; Bonneau, D; Mathieu, M; Der Kaloustian, V; Munnich, A; Kaplan, J

    1996-01-01

    Usher syndrome type I (US1) is an autosomal recessive condition in which three different genes have been already localised (USH1A, USH1B, and USH1C on chromosomes 14q32, 11q13, and 11p15 respectively). The genetic heterogeneity of US1 has been confirmed in a previous study by linkage analysis of 20 French pedigrees. Here, we report the genetic exclusion of the three previously reported loci in two large multiplex families of Moroccan and Pakistani origin, suggesting the existence of at least a fourth locus in Usher syndrome type I. PMID:8825055

  7. Association study between the TNXB locus and schizophrenia in a Japanese population.

    PubMed

    Tochigi, Mamoru; Zhang, Xuan; Ohashi, Jun; Hibino, Hiroyuki; Otowa, Takeshi; Rogers, Mark; Kato, Tadafumi; Okazaki, Yuji; Kato, Nobumasa; Tokunaga, Katsushi; Sasaki, Tsukasa

    2007-04-01

    The chromosome 6p21-24 region, which contains the human leukocyte antigen (HLA) region, has been suggested as an important locus for a susceptibility gene for schizophrenia. Recently, a significant association between schizophrenia and the TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region, was observed. Few studies have further investigated the region in schizophrenia. In the present study, we investigated the region in a Japanese population. Subjects included 241 patients with schizophrenia and 290 controls. Twenty-six single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and rs204887) as in the previous study were associated with schizophrenia (P = 0.034 and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and haplotype around it were also suggested to associate with the disease, consistent with another previous study (P = 0.041 and permutation P = 0.024, respectively, uncorrected). Although these associations became insignificant after Bonferroni correction, the findings might provide support for the association of the TNXB locus or its adjacent region of the NOTCH4 locus with schizophrenia. PMID:17192952

  8. 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.

  9. 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.

  10. 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

  11. Mitotic Chromosome Loss in a Disomic Haploid of SACCHAROMYCES CEREVISIAE

    PubMed Central

    Campbell, D. A.; Fogel, S.; Lusnak, K.

    1975-01-01

    Experiments designed to characterize the incidence of mitotic chromosome loss in a yeast disomic haploid were performed. The selective methods employed utilize the non-mating property of strains disomic for linkage group III and heterozygous at the mating type locus. The principal findings are: (1) The frequency of spontaneous chromosome loss in the disome is of the order 10-4 per cell; this value approximates the frequency in the same population of spontaneous mitotic exchange resulting in homozygosity at the mating type locus. (2) The recovered diploids are pure clones, and thus represent unique events in the disomic haploid. (3) Of the euploid chromosomes recovered after events leading to chromosome loss, approximately 90% retain the parental marker configuration expected from segregation alone; however, the remainder are recombinant for marker genes, and are the result of mitotic exchanges in the disome, especially in regions near the centromere. The recombinant proportion significantly exceeds that expected if chromosome loss and mitotic exchange in the disome were independent events. The data are consistent with a model proposing mitotic nondisjunction as the event responsible for chromosome loss in the disomic haploid. PMID:1092597

  12. 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. PMID:27033694

  13. 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.

  14. 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.

  15. 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

  16. Confirmation of Single-Locus Sex Determination and Female Heterogamety in Willow Based on Linkage Analysis.

    PubMed

    Chen, Yingnan; Wang, Tiantian; 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

  17. 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

  18. 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

  19. The Precarious Prokaryotic Chromosome

    PubMed Central

    2014-01-01

    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. PMID:24633873

  20. 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. PMID:24633873

  1. 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

  2. Linkage of Inflammatory Bowel Disease to Human Chromosome 6p

    PubMed Central

    Hampe, Jochen; Shaw, Sarah H.; Saiz, Robert; Leysens, Nancy; Lantermann, Annette; Mascheretti, Silvia; Lynch, Nicholas J.; MacPherson, Andrew J. S.; Bridger, Stephen; van Deventer, Sander; Stokkers, Pieter; Morin, Phil; Mirza, Mudassar M.; Forbes, Alastair; Lennard-Jones, John E.; Mathew, Christopher G.; Curran, Mark E.; Schreiber, Stefan

    1999-01-01

    Summary Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Given the immunologic dysregulation in IBD, the human-leukocyte-antigen region on chromosome 6p is of significant interest. Previous association and linkage analysis has provided conflicting evidence as to the existence of an IBD-susceptibility locus in this region. Here we report on a two-stage linkage and association analysis of both a basic population of 353 affected sibling pairs (ASPs) and an extension of this population to 428 white ASPs of northern European extraction. Twenty-eight microsatellite markers on chromosome 6 were genotyped. A peak multipoint LOD score of 4.2 was observed, at D6S461, for the IBD phenotype. A transmission/disequilibrium test (TDT) result of P=.006 was detected for D6S426 in the basic population and was confirmed in the extended cohort (P=.004; 97 vs. 56 transmissions). The subphenotypes of Crohn disease, ulcerative colitis, and mixed IBD contributed equally to this linkage, suggesting a general role for the chromosome 6 locus in IBD. Analysis of five single-nucleotide polymorphisms in the TNFA and LTA genes did not reveal evidence for association of these important candidate genes with IBD. In summary, we provide firm linkage evidence for an IBD-susceptibility locus on chromosome 6p and demonstrate that TNFA and LTA are unlikely to be susceptibility loci for IBD. PMID:10577918

  3. 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

  4. 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

  5. The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation

    SciTech Connect

    Migeon, B.R.; Luo, S.; Jani, M.; Jeppesen, P.

    1994-09-01

    Mental retardation and a constellation of congenital malformations not usually associated with Turner syndrome are seen in some females with a mosaic 45,X/46,X,r(X) karyotype. Studies of these females show that the XIST locus on their tiny ring X chromosomes is either not present or not expressed. As XIST transcription is well correlated with inactivation of the X chromosome in female somatic cells and spermatogonia, nonexpression of the locus even if it is present suggests that these chromosomes are transcriptionally active. The authors examined the transcriptional activity of ring X chromosomes lacking XIST expression (XIST E{sup {minus}}), from three females with severe phenotypes. The two tiny ring X chromosomes studied with an antibody specific for the acetylated isoforms of histone H4 marking transcribed chromatin domains were labeled at a level consistent with their being active. The authors also examined two of the XIST E{sup {minus}} ring chromosomes to determine whether genes that are normally silent on an inactive X are expressed from these chromosomes. Analyses of hybrid cells show that TIMP, ZXDA, and ZCDB loci on the proximal short arm, and AR and PHKA1 loci on the long arm, are well expressed from the tiny ring X chromosome lacking XIST DNA. Studies of the ring chromosome that has XIST DNA but does not transcribe it show that its AR allele is transcribed along with the one on the normal X allele. These findings provide compelling evidence that (1) ring X chromosomes associated with severe phenotypes are unable to undergo X chromosome inactivation; (2) they represent chromosomal mutations affecting cis inactivation; and (3) the severe phenotype is due to functional disomy resulting from lack of dosage compensation for genes present within the ring chromosome. 31 refs., 5 figs., 1 tab.

  6. DNA linkage analysis of X chromosome-linked chronic granulomatous disease.

    PubMed Central

    Baehner, R L; Kunkel, L M; Monaco, A P; Haines, J L; Conneally, P M; Palmer, C; Heerema, N; Orkin, S H

    1986-01-01

    Chronic granulomatous disease (CGD) is a disorder of phagocytes that is usually inherited as an X chromosome-linked trait. Previous family studies suggested that the CGD locus resides on the distal short arm (Xp22-Xpter). Using cloned, polymorphic DNA probes we have performed a linkage analysis within CGD families that suggests a more proximal location (Xp21). In addition, the CGD locus is proximal to the Duchenne muscular dystrophy locus and lies within a broad region of Xp in which recombination appears to be greater than anticipated on the basis of physical distance between markers. Regional localization of the X chromosome CGD locus should facilitate molecular cloning of the CGD gene and molecular dissection of the phagocyte oxidase system. Images PMID:3010296

  7. Molecular characterization of the S locus in two self-incompatible Brassica napus lines.

    PubMed Central

    Yu, K; Schafer, U; Glavin, T L; Goring, D R; Rothstein, S J

    1996-01-01

    In Brassica species, self-incompatibility has been mapped genetically to a single chromosomal location. In this region, there are two closely linked genes coding for the S locus glycoprotein (SLG) and S locus receptor kinase (SRK). They appear to comprise the pistil component of the self-incompatibility reaction. SLG and SRK are thought to recognize an unknown pollen component on the incompatible pollen, and the gene encoding this pollen component must also be linked to the SLG and SRK genes. To further our understanding of self-incompatibility, the chromosomal region carrying the SLG and SRK genes has been studied. The physical region between the SLG-910 and the SRK-910 genes in the Brassica napus W1 line was cloned, and a search for genes expressed in the anther revealed two additional S locus genes located downstream of the SLG-910 gene. Because these two genes are novel and are conserved at other S alleles, we designated them as SLL1 and SLL2 (for S locus-linked genes 1 and 2, respectively). The SLL1 gene is S locus specific, whereas the SLL2 gene is not only present at the S locus but is also present in other parts of the genomes in both self-incompatible and self-compatible Brassica ssp lines. Expression of the SLL1 gene is only detectable in anthers of self-incompatible plants and is developmentally regulated during anther development, whereas the SLL2 gene is expressed in anthers and stigmas in both self-incompatible and self-compatible plants, with the highest levels of expression occurring in the stigmas. Although SLL1 and SLL2 are linked to the S locus region, it is not clear whether these genes function in self-incompatibility or serve some other cellular roles in pollen-pistil functions. PMID:8989888

  8. 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

  9. 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.

  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. 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.

  12. Locus of Control and Interpersonal Attraction.

    ERIC Educational Resources Information Center

    Fagan, M. Michael

    1980-01-01

    The role of locus of control in interpersonal attraction was examined by administering 1) the Nowicki-Strickland Locus of Control Scale and 2) a sociometric test of friendship to 200 eighth graders. (CM)

  13. Chromosomal location of three spectrin genes: relationship to the inherited hemolytic anemias of mouse and man.

    PubMed Central

    Birkenmeier, C S; McFarland-Starr, E C; Barker, J E

    1988-01-01

    Three genetic loci in the mouse affect the synthesis and assembly of the erythrocyte membrane skeleton. The spherocytosis and jaundiced loci affect the membrane skeletal protein known as spectrin. The normoblastosis locus affects the spectrin binding protein called ankyrin. We have obtained genetic data that define the linkage relationships among three spectrin genes and the spherocytosis and jaundiced loci. The erythroid alpha-spectrin gene is tightly linked to the spherocytosis locus on chromosome 1 and the jaundiced locus is on chromosome 12, tightly linked to the erythroid beta-spectrin gene. The brain alpha-spectrin (alpha-fodrin) gene is located on the centromeric end of chromosome 2 and is not closely linked to any previously mapped erythroid or neurological mutation. These results are consistent with the hypothesis that defects in the alpha- and beta-spectrin genes cause the spherocytosis and jaundiced hemolytic anemias in mice. All five loci studied are located within chromosomal segments that are conserved between mouse and man. Analysis of the data from the chromosome 12 study defines a new order for the genes on that chromosome and delineates the largest mouse/human conserved chromosomal segment yet known. Images PMID:3186715

  14. 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

  15. The evolution of a genetic locus encoding small serine proteinase inhibitors ⋆

    PubMed Central

    Clauss, Adam; Lilja, Hans; Lundwall, Åke

    2007-01-01

    We previously identified a locus on human chromosome 20 that encompasses 14 genes of postulated WFDC-type proteinase inhibitors with a potential role in innate immunity. In an extended study, homologous loci are here described on mouse chromosome 2, rat chromosome 3, and dog chromosome 24. As in humans, the murine and canine loci are divided into two sub-loci separated by 0.2 Mb. The majority of genes are conserved in all species, but there are also species-specific gains and losses of genes, e.g., several duplications have yielded four SLPI genes in the rat and, most surprisingly, there is no murine elafin gene. Two human pseudogenes were identified due to the discovery of functional rodent genes. The conservation of different WFDC domains varies considerably, and it is hypothesized that this reflects a dual role of WFDC inhibitors in natural immunity, which is directed both against microbes and proinflammatory cells. PMID:15950183

  16. 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.

  17. 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.

  18. 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.

  19. 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)

  20. Chromosomal development of cancer

    SciTech Connect

    1993-12-31

    Chapter 30, describes the chromosomal development of cancer. It has been established through cytological research that the number of chromosomes in cancer cells often deviates greatly from the usual number in healthy cells of the host organism. This chapter includes discussions on chromosome studies in ascites tumors, stemline and tumor development, mitotic aberrations in cancer, and selection and tumor progression. 25 refs., 2 figs.

  1. 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.

  2. 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…

  3. 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.

  4. Individual chromosome assignment and chromosomal collinearity in Gossypium thurberi, G. trilobum and D subgenome of G. barbadense revealed by BAC-FISH.

    PubMed

    Gan, Yimei; Chen, Dan; Liu, Fang; Wang, Chunying; Li, Shaohui; Zhang, Xiangdi; Wang, Yuhong; Peng, Renhai; Wang, Kunbo

    2011-01-01

    The experiment on individual chromosome assignments and chromosomal diversity was conducted using a multi-probe fluorescence in situ hybridization (FISH) system in D subgenome of tetraploid Gossypium barbadense (D(b)), G. thurberi (D(1)) and G. trilobum (D(8)), which the later two were the possible subgenome donors of tetraploid cottons. The FISH probes contained a set of bacterial artificial chromosome (BAC) clones specific to 13 individual chromosomes from D subgenome of G. hirsutum (D(h)), a D genome centromere-specific BAC clone 150D24, 45S and 5S ribosomal DNA (rDNA) clones, respectively. All tested chromosome orientations were confirmed by the centromere-specific BAC probe. In D(1) and D(8), four 45S rDNA loci were found assigning at the end of the short arm of chromosomes 03, 07, 09 and 11, while one 5S rDNA locus was successfully marked at pericentromeric region of the short arm of chromosome 09. In D(b), three 45S rDNA loci and two 5S rDNA loci were found out. Among them, two 45S rDNA loci were located at the terminal of the short arm of chromosomes D(b)07 and D(b)09, whilst one 5S rDNA locus was found situating near centromeric region of the short arm of chromosome D(b)09. The positions of the BAC clones specific to the 13 individual chromosomes from D(h) were compared between D(1), D(8) and D(b). The result showed the existence of chromosomal collinearity within D(1) and D(8), and as well between them and D(b). The results will serve as a base for understanding chromosome structure of cotton and polyploidy evolution of cotton genome and will provide bio-information for assembling the sequences of finished and the on-going cotton whole genome sequencing projects. PMID:21952206

  5. Microsatellite and Chromosome Evolution of Parthenogenetic Sitobion Aphids in Australia

    PubMed Central

    Sunnucks, P.; England, P. R.; Taylor, A. C.; Hales, D. F.

    1996-01-01

    Single-locus microsatellite variation correlated perfectly with chromosome number in Sitobion miscanthi aphids. The microsatellites were highly heterozygous, with up to 10 alleles per locus in this species. Despite this considerable allelic variation, only seven different S. miscanthi genotypes were discovered in 555 individuals collected from a wide range of locations, hosts and sampling periods. Relatedness between genotypes suggests only two successful colonizations of Australia. There was no evidence for genetic recombination in 555 S. miscanthi so the occurrence of recent sexual reproduction must be near zero. Thus diversification is by mutation and chromosomal rearrangement alone. Since the aphids showed no sexual recombination, microsatellites can mutate without meiosis. Five of seven microsatellite differences were a single repeat unit, and one larger jump is likely. The minimum numbers of changes between karyotypes corresponded roughly one-to-one with microsatellite allele changes, which suggests very rapid chromosomal evolution. A chromosomal fission occurred in a cultured line, and a previously unknown chromosomal race was detected. All 121 diverse S. near fragariae were heterozygous but revealed only one genotype. This species too must have a low rate of sexual reproduction and few colonizations of Australia. PMID:8889535

  6. 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

  7. THE WHEAT D-GENOME HMW-GLUTENIN LOCUS:BAC SEQUENCING, GENE DISTRIBUTION, AND RETROTRANSPOSON CLUSTERS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A bacterial-artificial-chromosome (BAC) clone from the genome of Triticum tauschii, the D-genome ancestor of hexaploid bread wheat, was sequenced and the presence of the two paralogous x- and y- type high-molecular-weight (HMW) glutenin genes of the Glu-D1 locus was confirmed. These two genes occur...

  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. 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

  10. A large duplication involving the IHH locus mimics acrocallosal syndrome

    PubMed Central

    Yuksel-Apak, Memnune; Bögershausen, Nina; Pawlik, Barbara; Li, Yun; Apak, Selcuk; Uyguner, Oya; Milz, Esther; Nürnberg, Gudrun; Karaman, Birsen; Gülgören, Ayan; Grzeschik, Karl-Heinz; Nürnberg, Peter; Kayserili, Hülya; Wollnik, Bernd

    2012-01-01

    Indian hedgehog (Ihh) signaling is a major determinant of various processes during embryonic development and has a pivotal role in embryonic skeletal development. A specific spatial and temporal expression of Ihh within the developing limb buds is essential for accurate digit outgrowth and correct digit number. Although missense mutations in IHH cause brachydactyly type A1, small tandem duplications involving the IHH locus have recently been described in patients with mild syndactyly and craniosynostosis. In contrast, a ∼600-kb deletion 5′ of IHH in the doublefoot mouse mutant (Dbf) leads to severe polydactyly without craniosynostosis, but with craniofacial dysmorphism. We now present a patient resembling acrocallosal syndrome (ACS) with extensive polysyndactyly of the hands and feet, craniofacial abnormalities including macrocephaly, agenesis of the corpus callosum, dysplastic and low-set ears, severe hypertelorism and profound psychomotor delay. Single-nucleotide polymorphism (SNP) array copy number analysis identified a ∼900-kb duplication of the IHH locus, which was confirmed by an independent quantitative method. A fetus from a second pregnancy of the mother by a different spouse showed similar craniofacial and limb malformations and the same duplication of the IHH-locus. We defined the exact breakpoints and showed that the duplications are identical tandem duplications in both sibs. No copy number changes were observed in the healthy mother. To our knowledge, this is the first report of a human phenotype similar to the Dbf mutant and strikingly overlapping with ACS that is caused by a copy number variation involving the IHH locus on chromosome 2q35. PMID:22234151

  11. Chromosomes, conflict, and epigenetics: chromosomal speciation revisited.

    PubMed

    Brown, Judith D; O'Neill, Rachel J

    2010-01-01

    Since Darwin first noted that the process of speciation was indeed the "mystery of mysteries," scientists have tried to develop testable models for the development of reproductive incompatibilities-the first step in the formation of a new species. Early theorists proposed that chromosome rearrangements were implicated in the process of reproductive isolation; however, the chromosomal speciation model has recently been questioned. In addition, recent data from hybrid model systems indicates that simple epistatic interactions, the Dobzhansky-Muller incompatibilities, are more complex. In fact, incompatibilities are quite broad, including interactions among heterochromatin, small RNAs, and distinct, epigenetically defined genomic regions such as the centromere. In this review, we will examine both classical and current models of chromosomal speciation and describe the "evolving" theory of genetic conflict, epigenetics, and chromosomal speciation. PMID:20438362

  12. 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

  13. 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. PMID:27405443

  14. 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.

  15. Human and mouse chromosomal mapping of the myeloid cell leukemia-1 gene: MCL1 maps to human chromosome 1q21, a region that is frequently altered in preneoplastic and neoplastic disease

    SciTech Connect

    Craig, R.W.; Zhou, P.; Kozopas, K.M.

    1994-09-15

    The MCL1 gene, recently identified in a myeloid leukemia cell line, has sequence similarity to BCL2, the gene at the t(14;18) translocation in follicular lymphoma. The chromosomal location of MCL1 has now been determined. The human locus (MCL1) was mapped to the long arm of human chromosome 1q21, using the methods of in situ hybridization and somatic cell hybrid analysis. In the mouse, MCL1-related sequences were mapped to positions on two mouse chromosomes (chromosomes 3 and 5), using haplotype analysis of an interspecific cross. The location of the locus on mouse chromosome 3 (Mcl1) was homologous to that of MCL1 on human chromosome 1; the second locus (Mcl-rs on mouse chromosome 5) may represent a pseudogene. The proximal long arm of human chromosome 1, where MCL1 is located, is duplicated and/or rearranged in a variety of preneoplastic and neoplastic diseases including hematologic diseases and solid tumors. MCL1 is thus a candidate gene for involvement in cancer. 46 refs., 2 figs., 3 tabs.

  16. 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.

  17. 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.

  18. Sorting of chromosome 13 from lymphoblastoid cell lines derived from patients with Wilson disease

    SciTech Connect

    Nasedkina, T.V.; Polesskaya, A.N.; Surkov, S.A.; Poletaev, A.I. ); Aksenov, N.; Zenin, V.V. )

    1993-01-01

    Lymphoblastoid cell lines were established from patients with Wilson disease (WD) which maps to human chromosome 13 and served as a source of chromosomes. The authors used a modified isolation procedure to increase the yield of metaphase chromosomes and additional purification of the chromosome suspension on Percoll gradient to achieve more stable sorting conditions. Vibariate flow analysis using dual laser cell-sorter, ATC-3000, showed a sufficient resolution of the flow karyotype and a low level of debris. They sorted chromosome 13 at a speed of up to 5,000 chr/sec, providing about 2 million chromosomes per day. The purity of the sorted fraction was about 90%. The fractions will be further used to construct cosmid libraries to facilitate studies of the WD locus.

  19. 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.

  20. 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

  1. Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome

    PubMed Central

    Du, Meijun; Yuan, Tiezheng; Schilter, Kala F.; Dittmar, Rachel L.; Mackinnon, Alexander; Huang, Xiaoyi; Tschannen, Michael; Worthey, Elizabeth; Jacob, Howard; Xia, Shu; Gao, Jianzhong; Tillmans, Lori; Lu, Yan; Liu, Pengyuan; Thibodeau, Stephen N.; Wang, Liang

    2015-01-01

    Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression. PMID:25149474

  2. Linkage mapping of a polymorphic plumage locus associated with intermorph incompatibility in the Gouldian finch (Erythrura gouldiae).

    PubMed

    Kim, K-W; Griffith, S C; Burke, T

    2016-04-01

    Colour polymorphism is known to facilitate speciation but the genetic basis of animal pigmentation and how colour polymorphisms contribute to speciation is poorly understood. Restricted recombination may promote linkage disequilibrium between the colour locus and incompatibility genes. Genomic rearrangement and the position of relevant loci within a chromosome are important factors that influence the frequency of recombination. Therefore, it is important to know the position of the colour locus, gene order and recombination landscape of the chromosome to understand the mechanism that generates incompatibilities between morphs. Recent studies showed remarkable pre- and postzygotic incompatibilities between sympatric colour morphs of the Gouldian finch (Erythrura gouldiae), in which head feather colour is genetically determined by a single sex-linked locus, Red. We constructed a genetic map for the Z chromosome of the Gouldian finch (male-specific map distance=131 cM), using 618 captive-bred birds and 34 microsatellite markers, to investigate the extent of inter- and intraspecific genomic rearrangements and variation in recombination rate within the Z chromosome. We refined the location of the Red locus to a ~7.2-cM interval in a region with a moderate recombination rate but outside the least-recombining, putative centromeric region. There was no evidence of chromosome-wide genomic rearrangements between the chromosomes carrying the red or black alleles with the current marker resolution. This work will contribute to identifying the causal gene, which will in turn enable alternative explanations for the association between incompatibility and colouration, such as fine-scale linkage disequilibrium, genomic rearrangements and pleiotropy, to be tested. PMID:26786066

  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. 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.

  5. 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.

  6. Escherichia coli Chromosomal Loci Segregate from Midcell with Universal Dynamics.

    PubMed

    Cass, Julie A; Kuwada, Nathan J; Traxler, Beth; Wiggins, Paul A

    2016-06-21

    The structure of the Escherichia coli chromosome is inherently dynamic over the duration of the cell cycle. Genetic loci undergo both stochastic motion around their initial positions and directed motion to opposite poles of the rod-shaped cell during segregation. We developed a quantitative method to characterize cell-cycle dynamics of the E. coli chromosome to probe the chromosomal steady-state mobility and segregation process. By tracking fluorescently labeled chromosomal loci in thousands of cells throughout the entire cell cycle, our method allows for the statistical analysis of locus position and motion, the step-size distribution for movement during segregation, and the locus drift velocity. The robust statistics of our detailed analysis of the wild-type E. coli nucleoid allow us to observe loci moving toward midcell before segregation occurs, consistent with a replication factory model. Then, as segregation initiates, we perform a detailed characterization of the average segregation velocity of loci. Contrary to origin-centric models of segregation, which predict distinct dynamics for oriC-proximal versus oriC-distal loci, we find that the dynamics of loci were universal and independent of genetic position. PMID:27332118

  7. Ac-Induced Instability at the Xanthophyllic Locus of Tomato

    PubMed Central

    Peterson, P. W.; Yoder, J. I.

    1993-01-01

    To detect genomic instability caused by Ac elements in transgenic tomatoes, we used the incompletely dominant mutation Xanthophyllic-1 (Xa-1) as a whole plant marker gene. Xa-1 is located on chromosome 10 and in the heterozygote state causes leaves to be yellow. Transgenic Ac-containing tomato plants which differed in the location and number of their Ac elements were crossed to Xa-1 tester lines and F(1) progeny were scored for aberrant somatic sectoring. Of 800 test and control F(1) progeny screened, only four plants had aberrantly high levels of somatic sectors. Three of the plants had twin sectors consisting of green tissue adjacent to white tissue, and the other had twin sectors comprised of green tissue adjacent to tissue more yellow than the heterozygote background. Sectoring was inherited and the two sectoring phenotypes mapped to opposite homologs of chromosome 10; the green/yellow sectoring phenotype mapped in coupling to Xa-1 while the green/white sectoring phenotype mapped in repulsion. The two sectoring phenotypes cosegregated with different single, non-rearranged Acs, and loss of these Acs from the genome corresponded to the loss of sectoring. Sectoring was still observed after transposition of the Ac to a new site which indicated that sectoring was not limited to a single locus. In both sectored lines, meiotic recombination of the sectoring Ac to the opposite homolog caused the phenotype to switch between the green/yellow and the green/white phenotypes. Thus the two different sectoring phenotypes arose from the same Ac-induced mechanism; the phenotype depended on which chromosome 10 homolog the Ac was on. We believe that the twin sectors resulted from chromosome breakage mediated by a single intact, transposition-competent Ac element. PMID:8394266

  8. 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

  9. High-Resolution Two-Locus Clonal Typing of Extraintestinal Pathogenic Escherichia coli

    PubMed Central

    Johnson, James R.; Tchesnokova, Veronika; Billig, Mariya; Dykhuizen, Daniel; Riddell, Kim; Rogers, Peggy; Qin, Xuan; Butler-Wu, Susan; Cookson, Brad T.; Fang, Ferric C.; Scholes, Delia; Chattopadhyay, Sujay

    2012-01-01

    Multilocus sequence typing (MLST) is usually based on the sequencing of 5 to 8 housekeeping loci in the bacterial chromosome and has provided detailed descriptions of the population structure of bacterial species important to human health. However, even strains with identical MLST profiles (known as sequence types or STs) may possess distinct genotypes, which enable different eco- or pathotypic lifestyles. Here we describe a two-locus, sequence-based typing scheme for Escherichia coli that utilizes a 489-nucleotide (nt) internal fragment of fimH (encoding the type 1 fimbrial adhesin) and the 469-nt internal fumC fragment used in standard MLST. Based on sequence typing of 191 model commensal and pathogenic isolates plus 853 freshly isolated clinical E. coli strains, this 2-locus approach—which we call CH (fumC/fimH) typing—consistently yielded more haplotypes than standard 7-locus MLST, splitting large STs into multiple clonal subgroups and often distinguishing different within-ST eco- and pathotypes. Furthermore, specific CH profiles corresponded to specific STs, or ST complexes, with 95% accuracy, allowing excellent prediction of MLST-based profiles. Thus, 2-locus CH typing provides a genotyping tool for molecular epidemiology analysis that is more economical than standard 7-locus MLST but has superior clonal discrimination power and, at the same time, corresponds closely to MLST-based clonal groupings. PMID:22226951

  10. Analysis of meiotic segregation, using single-sperm typing: meiotic drive at the myotonic dystrophy locus.

    PubMed Central

    Leeflang, E. P.; McPeek, M. S.; Arnheim, N.

    1996-01-01

    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. PMID:8808606

  11. 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.

  12. A 12 megabase restriction map at the cystic fibrosis locus.

    PubMed Central

    Fulton, T R; Bowcock, A M; Smith, D R; Daneshvar, L; Green, P; Cavalli-Sforza, L L; Donis-Keller, H

    1989-01-01

    We have constructed a physical map of the chromosomal region containing the cystic fibrosis locus using seven DNA markers and pulsed-field gel electrophoresis methods. The map includes cleavage sites for 8 rare-cutting restriction enzymes and spans over 12 megabases (Mb) of DNA, with one unlinked probe covering an additional 5 Mb. To our knowledge, this is the largest segment of human DNA which has been restriction-mapped to date. We can identify thirteen putative HTF islands spaced at intervals of 0.3-3.2 Mb. The region between loci D7S8 and MET, where the CF gene lies, includes 1.4-1.9 Mb of DNA. Images PMID:2911467

  13. 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

  14. 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

  15. Transcription facilitates sister chromatid cohesion on chromosomal arms.

    PubMed

    Bhardwaj, Shweta; Schlackow, Margarita; Rabajdova, Miroslava; Gullerova, Monika

    2016-08-19

    Cohesin is a multi-subunit protein complex essential for sister chromatid cohesion, gene expression and DNA damage repair. Although structurally well studied, the underlying determinant of cohesion establishment on chromosomal arms remains enigmatic. Here, we show two populations of functionally distinct cohesin on chromosomal arms using a combination of genomics and single-locus specific DNA-FISH analysis. Chromatin bound cohesin at the loading sites co-localizes with Pds5 and Eso1 resulting in stable cohesion. In contrast, cohesin independent of its loader is unable to maintain cohesion and associates with chromatin in a dynamic manner. Cohesive sites coincide with highly expressed genes and transcription inhibition leads to destabilization of cohesin on chromatin. Furthermore, induction of transcription results in de novo recruitment of cohesive cohesin. Our data suggest that transcription facilitates cohesin loading onto chromosomal arms and is a key determinant of cohesive sites in fission yeast. PMID:27084937

  16. Two novel tumor suppressor gene loci on chromosome 6q and 15q in human osteosarcoma identified through comparative study of allelic imbalances in mouse and man.

    PubMed

    Nathrath, Michaela H; Kuosaite, Virginija; Rosemann, Michael; Kremer, Marcus; Poremba, Christopher; Wakana, Shigeharu; Yanagi, Masayuki; Nathrath, Walter B J; Höfler, Heinz; Imai, Kenji; Atkinson, Michael J

    2002-08-29

    We have performed a comparative study of allelic imbalances in human and murine osteosarcomas to identify genetic changes critical for osteosarcomagenesis. Two adjacent but discrete loci on mouse chromosome 9 were found to show high levels of allelic imbalance in radiation-induced osteosarcomas arising in (BALB/cxCBA/CA) F1 hybrid mice. The syntenic human chromosomal regions were investigated in 42 sporadic human osteosarcomas. For the distal locus (OSS1) on mouse chromosome 9 the syntenic human locus was identified on chromosome 6q14 and showed allelic imbalance in 77% of the cases. Comparison between the human and mouse syntenic regions narrowed the locus down to a 4 Mbp fragment flanked by the marker genes ME1 and SCL35A1. For the proximal locus (OSS2) on mouse chromosome 9, a candidate human locus was mapped to chromosome 15q21 in a region showing allelic imbalance in 58% of human osteosarcomas. We have used a combination of synteny and microsatellite mapping to identify two potential osteosarcoma suppressor gene loci. This strategy represents a powerful tool for the identification of new genes important for the formation of human tumors. PMID:12185601

  17. 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

  18. 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

  19. Susceptibility to renal carcinoma in the Eker rat involves a tumor suppressor gene on chromosome 10.

    PubMed Central

    Yeung, R S; Buetow, K H; Testa, J R; Knudson, A G

    1993-01-01

    Germ-line mutations of tumor suppressor genes confer strong predisposition to tumor formation. In the rat, a form of dominantly inherited renal carcinoma (RC) results in multiple chromophobe cell tumors that resemble the human disease, and heterozygous carriers (RC/+) are highly susceptible to environmental agents (radiation and chemical carcinogens), making it a desirable model to study epithelial carcinogenesis. By linkage analysis, the locus of the inherited RC mutation was mapped to rat chromosomal band 10q12, near the protamine locus (logarithm of odds score = 17.96). Renal tumors also showed a loss of heterozygosity at this locus, lending support to the recessive nature of this putative tumor suppressor gene. Our result suggested that the human homolog of the RC gene may reside on human chromosome 16, not known to be altered commonly in human RC. Images Fig. 1 Fig. 3 Fig. 4 PMID:8103600

  20. Chromosome Organization and Replisome Dynamics in Mycobacterium smegmatis

    PubMed Central

    McKinney, John D.

    2015-01-01

    ABSTRACT Subcellular organization of the bacterial nucleoid and spatiotemporal dynamics of DNA replication and segregation have been studied intensively, but the functional link between these processes remains poorly understood. Here we use quantitative time-lapse fluorescence microscopy for single-cell analysis of chromosome organization and DNA replisome dynamics in Mycobacterium smegmatis. We report that DNA replication takes place near midcell, where, following assembly of the replisome on the replication origin, the left and right replication forks colocalize throughout the replication cycle. From its initial position near the cell pole, a fluorescently tagged chromosomal locus (attB, 245° from the origin) moves rapidly to the replisome complex just before it is replicated. The newly duplicated attB loci then segregate to mirror-symmetric positions relative to midcell. Genetic ablation of ParB, a component of the ParABS chromosome segregation system, causes marked defects in chromosome organization, condensation, and segregation. ParB deficiency also results in mislocalization of the DNA replication machinery and SMC (structural maintenance of chromosome) protein. These observations suggest that ParB and SMC play important and overlapping roles in chromosome organization and replisome dynamics in mycobacteria. PMID:25691587

  1. Turnover of Sex Chromosomes in Celebensis Group Medaka Fishes.

    PubMed

    Myosho, Taijun; Takehana, Yusuke; Hamaguchi, Satoshi; Sakaizumi, Mitsuru

    2015-12-01

    Sex chromosomes and the sex-determining (SD) gene are variable in vertebrates. In particular, medaka fishes in the genus Oryzias show an extremely large diversity in sex chromosomes and the SD gene, providing a good model to study the evolutionary process by which they turnover. Here, we investigated the sex determination system and sex chromosomes in six celebensis group species. Our sex-linkage analysis demonstrated that all species had an XX-XY sex determination system, and that the Oryzias marmoratus and O. profundicola sex chromosomes were homologous to O. latipes linkage group (LG) 10, while those of the other four species, O. celebensis, O. matanensis, O. wolasi, and O. woworae, were homologous to O. latipes LG 24. The phylogenetic relationship suggested a turnover of the sex chromosomes from O. latipes LG 24 to LG 10 within this group. Six sex-linkage maps showed that the former two and the latter four species shared a common SD locus, respectively, suggesting that the LG 24 acquired the SD function in a common ancestor of the celebensis group, and that the LG 10 SD function appeared in a common ancestor of O. marmoratus and O. profundicola after the divergence of O. matanensis. Additionally, fine mapping and association analysis in the former two species revealed that Sox3 on the Y chromosome is a prime candidate for the SD gene, and that the Y-specific 430-bp insertion might be involved in its SD function. PMID:26497145

  2. A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk

    PubMed Central

    Heinig, Matthias; Petretto, Enrico; Wallace, Chris; Bottolo, Leonardo; Rotival, Maxime; Lu, Han; Li, Yoyo; Sarwar, Rizwan; Langley, Sarah R.; Bauerfeind, Anja; Hummel, Oliver; Lee, Young-Ae; Paskas, Svetlana; Rintisch, Carola; Saar, Kathrin; Cooper, Jason; Buchan, Rachel; Gray, Elizabeth E.; Cyster, Jason G.; Erdmann, Jeanette; Hengstenberg, Christian; Maouche, Seraya; Ouwehand, Willem H.; Rice, Catherine M.; Samani, Nilesh J; Schunkert, Heribert; Goodall, Alison H; Schulz, Herbert; Roider, Helge; Vingron, Martin; Blankenberg, Stefan; Münzel, Thomas; Zeller, Tanja; Szymczak, Silke; Ziegler, Andreas; Tiret, Laurence; Smyth, Deborah J.; Pravenec, Michal; Aitman, Timothy J.; Cambien, Francois; Clayton, David; Todd, John A.; Hubner, Norbert; Cook, Stuart A.

    2013-01-01

    Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases. Here, we used integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF7)1-driven inflammatory network (iDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and was regulated in multiple tissues by a locus on rat chromosome 15q25. At this locus, Epstein-Barr virus induced gene 2 (Ebi2 or Gpr183), which we localised to macrophages and is known to control B lymphocyte migration2,3, regulated the iDIN. The human chromosome 13q32 locus, orthologous to rat 15q25, controlled the human equivalent of iDIN, which was conserved in monocytes. For the macrophage-associated autoimmune disease type 1 diabetes (T1D) iDIN genes were more likely to associate with T1D susceptibility than randomly selected immune response genes (P = 8.85 × 10−6). The human locus controlling the iDIN, was associated with the risk of T1D at SNP rs9585056 (P = 7.0 × 10−10, odds ratio = 1.15), which was one of five SNPs in this region associated with EBI2 expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D. PMID:20827270

  3. Quantitative trait locus analysis for kernel width using maize recombinant inbred lines.

    PubMed

    Hui, G Q; Wen, G Q; Liu, X H; Yang, H P; Luo, Q; Song, H X; Wen, L; Sun, Y; Zhang, H M

    2015-01-01

    Maize (Zea mays L.) kernel width is one of the most important traits that is related to yield and appearance. To understand its genetic mechanisms more clearly, a recombinant inbred line (RIL) segregation population consisting of 239 RILs was used for quantitative trait locus (QTL) mapping for kernel width. We found four QTLs on chromosomes 3 (one), 5 (two), and 10 (one). The QTLs were close to their adjacent markers, with a range of 0-23.8 cM, and explained 6.2-19.7% of the phenotypic variation. The three QTLs on chromosomes 3 and 5 had positive additive effects, and to a certain extent increased kernel width, whereas the one on chromosome 10 exhibited negative additive effects and decreased kernel width. These results can be used for gene cloning and marker-assisted selection in maize-breeding programs. PMID:26600508

  4. Actin-dependent intranuclear repositioning of an active gene locus in vivo

    PubMed Central

    Dundr, Miroslav; Ospina, Jason K.; Sung, Myong-Hee; John, Sam; Upender, Madhvi; Ried, Thomas; Hager, Gordon L.; Matera, A. Gregory

    2007-01-01

    Although bulk chromatin is thought to have limited mobility within the interphase eukaryotic nucleus, directed long-distance chromosome movements are not unknown. Cajal bodies (CBs) are nuclear suborganelles that nonrandomly associate with small nuclear RNA (snRNA) and histone gene loci in human cells during interphase. However, the mechanism responsible for this association is uncertain. In this study, we present an experimental system to probe the dynamic interplay of CBs with a U2 snRNA target gene locus during transcriptional activation in living cells. Simultaneous four-dimensional tracking of CBs and U2 genes reveals that target loci are recruited toward relatively stably positioned CBs by long-range chromosomal motion. In the presence of a dominant-negative mutant of β-actin, the repositioning of activated U2 genes is markedly inhibited. This supports a model in which nuclear actin is required for these rapid, long-range chromosomal movements. PMID:18070915

  5. 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

  6. Y chromosomal DNA variation and the peopling of Japan.

    PubMed

    Hammer, M F; Horai, S

    1995-04-01

    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. PMID:7717406

  7. Plant sex chromosome evolution.

    PubMed

    Charlesworth, Deborah

    2013-01-01

    It is now well established that plants have an important place in studies of sex chromosome evolution because of the repeated independent evolution of separate sexes and sex chromosomes. There has been considerable recent progress in studying plant sex chromosomes. In this review, I focus on how these recent studies have helped clarify or answer several important questions about sex chromosome evolution, and I shall also try to clarify some common misconceptions. I also outline future work that will be needed to make further progress, including testing some important ideas by genetic, molecular, and developmental approaches. Systems with different ages can clearly help show the time course of events during changes from an ancestral co-sexual state (hermaphroditism or monoecy), and I will also explain how different questions can be studied in lineages whose dioecy or sex chromosomes evolved at different times in the past. PMID:23125359

  8. 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.

  9. Transcriptome and Allele Specificity Associated with a 3BL Locus for Fusarium Crown Rot Resistance in Bread Wheat

    PubMed Central

    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. 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

  11. The barley Frost resistance-H2 locus.

    PubMed

    Pasquariello, Marianna; Barabaschi, Delfina; Himmelbach, Axel; Steuernagel, Burkhard; Ariyadasa, Ruvini; Stein, Nils; Gandolfi, Francesco; Tenedini, Elena; Bernardis, Isabella; Tagliafico, Enrico; Pecchioni, Nicola; Francia, Enrico

    2014-03-01

    Frost resistance-H2 (Fr-H2) is a major QTL affecting freezing tolerance in barley, yet its molecular basis is still not clearly understood. To gain a better insight into the structural characterization of the locus, a high-resolution linkage map developed from the Nure × Tremois cross was initially implemented to map 13 loci which divided the 0.602 cM total genetic distance into ten recombination segments. A PCR-based screening was then applied to identify positive bacterial artificial chromosome (BAC) clones from two genomic libraries of the reference genotype Morex. Twenty-six overlapping BACs from the integrated physical-genetic map were 454 sequenced. Reads assembled in contigs were subsequently ordered, aligned and manually curated in 42 scaffolds. In a total of 1.47 Mbp, 58 protein-coding sequences were identified, 33 of which classified according to similarity with sequences in public databases. As three complete barley C-repeat Binding Factors (HvCBF) genes were newly identified, the locus contained13 full-length HvCBFs, four Related to AP2 Triticeae (RAPT) genes, and at least five CBF pseudogenes. The final overall assembly of Fr-H2 includes more than 90 % of target region: all genes were identified along the locus, and a general survey of Repetitive Elements obtained. We believe that this gold-standard sequence for the Morex Fr-H2 will be a useful genomic tool for structural and evolutionary comparisons with Fr-H2 in winter-hardy cultivars along with Fr-2 of other Triticeae crops. PMID:24442711

  12. 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

  13. Positional cloning of the mouse saccharin preference (Sac) locus

    PubMed Central

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

    2013-01-01

    Differences in sweetener intake among inbred strains of mice are partially determined by allelic variation of the saccharin preference (Sac) locus. Genetic and physical mapping limited a critical genomic interval containing Sac to a 194-kb DNA fragment. Sequencing and annotation of this region identified a gene (Tas1r3) encoding the third member of the T1R family of putative taste receptors, T1R3. Introgression by serial backcrossing of the 194-kb chromosomal fragment containing the Tas1r3 allele from the high-sweetener preferring C57BL/6ByJ strain onto the genetic background of the low-sweetener preferring 129P3/J strain rescued its low sweetener preference phenotype. Polymorphisms of Tas1r3 that are likely to have functional significance were identified using analysis of genomic sequences and sweetener preference phenotypes of genealogically distant mouse strains. Tas1r3 has two common haplotypes, consisting of six single nucleotide polymorphisms: one haplotype was found in mouse strains with elevated sweetener preference and the other in strains relatively indifferent to sweeteners. This study provides compelling evidence that Tas1r3 is equivalent to the Sac locus and that the T1R3 receptor responds to sweeteners. PMID:11555487

  14. 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. PMID:27233955

  15. 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

  16. Icelandic families with autosomal dominant polycystic kidney disease: families unlinked to chromosome 16p13.3 revealed by linkage analysis.

    PubMed

    Fossdal, R; Böthvarsson, M; Asmundsson, P; Ragnarsson, J; Peters, D; Breuning, M H; Jensson, O

    1993-07-01

    We have mainly used 3 highly polymorphic DNA markers, 3'HVR (D16S85), 16AC2.5 (D16S291) and SM7 (D16S283), flanking the PKD1 region on chromosome 16p13.3 to establish linkage status in seven Icelandic families with autosomal dominant polycystic kidney disease (ADPKD). In four families, the disease locus is in the PKD1 region, and three families are "unlinked" to chromosome 16p13.3. In one of the "unlinked" families, the disease locus is excluded from a part of the long arm of chromosome 2, and we support a theory of more than 2 loci being responsible for ADPKD. Our data confirm the location of the locus YNH24 (D2S44) to chromosome 2q13-q24. PMID:8340115

  17. 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

  18. Genetic architecture of sexual dimorphism in a subdioecious plant with a proto-sex chromosome.

    PubMed

    Spigler, Rachel B; Lewers, Kim S; Ashman, Tia-Lynn

    2011-04-01

    The rise of sexual dimorphism is thought to coincide with the evolution of sex chromosomes. Yet because sex chromosomes in many species are ancient, we lack empirical evidence of the earliest stages of this transition. We use QTL analysis to examine the genetic architecture of sexual dimorphism in subdioecious octoploid Fragaria virginiana. We demonstrate that the region housing the male-function locus controls the majority of quantitative variation in proportion fruit set, confirming the existence of a proto-sex chromosome, and houses major QTL for eight additional sexually dimorphic traits, consistent with theory and data from animals and plants with more advanced sex chromosomes. We also detected autosomal QTL, demonstrating contributions to phenotypic variation in sexually dimorphic traits outside the sex-determining region. Moreover, for proportion seed set we found significant epistatic interactions between autosomal QTL and the male-function locus, indicating sex-limited QTL. We identified linked QTL reflecting trade-offs between male and female traits expected from theory and positive integration of male traits. These findings indicate the potential for the evolution of greater sexual dimorphism. Involvement of linkage groups homeologous to the proto-sex chromosome in these correlations reflects the polyploid origin of F. virginiana and raises the possibility that chromosomes in this homeologous group were predisposed to become the sex chromosome. PMID:21062281

  19. 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

  20. 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

  1. Physical linkage of a GABAA receptor subunit gene to the DXS374 locus in human Xq28.

    PubMed Central

    Bell, M V; Bloomfield, J; McKinley, M; Patterson, M N; Darlison, M G; Barnard, E A; Davies, K E

    1989-01-01

    We report the physical linkage of the gene encoding one of the subunits of the GABAA receptor (GABRA3) to the polymorphic locus DXS374 on the human X chromosome at Xq28. X-linked manic depression and other psychiatric disorders have been mapped to this region, and thus GABRA3 is a potential candidate gene for these disorders. DXS374--and therefore GABRA3--lies distal to the fragile X locus at a recombination fraction of approximately .15. Images Figure 1 Figure 2 PMID:2574000

  2. The Regulation of White Locus Expression: A Dominant Mutant Allele at the White Locus of DROSOPHILA MELANOGASTER

    PubMed Central

    Bingham, Paul M.

    1980-01-01

    A new mutant allele (wDZL) at the white locus of Drosophila melanogaster is dominant to the wild-type allele, but apparently only when the two alleles are synapsed. When chromosomal rearrangements prevent somatic pairing between the two white alleles, wDZL is rendered recessive to wild type. This observation suggests that the dominance of wDZL is sensitive to a synapsis (transvection) effect. On the basis of this and other properties, it is proposed that wDZL causes the repression of transcription of a synapsed w+ allele, but not of a w+ allele elsewhere in the same nucleus. One model to account for this supposes that wDZL produces a repressor of white-locus transcription. This repressor is presumed to be so unstable that other white genes, removed from wDZL but in the same nucleus, are not detectably repressed. These properties may be simply understood if it is assumed that the repressor produced by the wDZL allele is an RNA molecule. PMID:17249039

  3. 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…

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Refined mapping of the G[sub M2] activator protein (GM2A) locus to 5q31. 3-q33. 1, distal to the spinal muscular atrophy locus

    SciTech Connect

    Heng, H.H.Q.; Xie, B.; Shi, X.M.; Tsui, L.C.; Mahuran, D.J. )

    1993-11-01

    The G[sub M2] activator locus (GM2A) had previously been considered as a candidate gene for some forms of spinal muscular atrophy (SMA; mapped to 5q11.2-q13.3). It was eliminated as a possible candidate because PCR-based mapping failed to localize the gene to chromosome 5, as was previously reported using an ELISA-based methodology. However, the authors demonstrated that the PCR primers used preferentially amplified a processed pseudogene (GM2AP) that was mapped to chromosome 3 and that GM2A was located on chromosome 5. In this report, they reconsider the candidacy of GM2A by refining its localization on chromosome 5 using fluorescence in situ hybridization. They localize GM2A to 5q31.3-q33.1; thus, it is not a candidate gene for SMA. 11 refs., 2 figs.

  11. 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

  12. 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

  13. A molecular description of mutations affecting the pollen component of the Nicotiana alata S locus.

    PubMed Central

    Golz, J F; Su, V; Clarke, A E; Newbigin, E

    1999-01-01

    Mutations affecting the self-incompatibility response of Nicotiana alata were generated by irradiation. Mutants in the M1 generation were selected on the basis of pollen tube growth through an otherwise incompatible pistil. Twelve of the 18 M1 plants obtained from the mutagenesis screen were self-compatible. Eleven self-compatible plants had mutations affecting only the pollen function of the S locus (pollen-part mutants). The remaining self-compatible plant had a mutation affecting only the style function of the S locus (style-part mutant). Cytological examination of the pollen-part mutant plants revealed that 8 had an extra chromosome (2n + 1) and 3 did not. The pollen-part mutation in 7 M1 plants was followed in a series of crosses. DNA blot analysis using probes for S-RNase genes (encoding the style function of the S locus) indicated that the pollen-part mutation was associated with an extra S allele in 4 M1 plants. In 3 of these plants, the extra S allele was located on the additional chromosome. There was no evidence of an extra S allele in the 3 remaining M1 plants. The breakdown of self-incompatibility in plants with an extra S allele is discussed with reference to current models of the molecular basis of self-incompatibility. PMID:10388830

  14. Intrachromosomal telomere-related sequences and gpt locus sensitivity to ionizing radiation

    SciTech Connect

    Oroskar, A.A.; Sedita, B.A; Schwartz, J.L.

    1994-12-31

    The Chinese hamster ovary cell line CHO-T510 contains a single copy of a stably integrated retroviral vector with a selectable marker, the E. coli xanthine-guanine phosphoribosyl transferase (gpt) gene. Previous studies on the CHO-T510 line showed that, in comparison with other genetic loci, the gpt locus was hypersensitive to mutation induction by ionizing radiation. Southern blot analyses of a set of 20-26 gpt{sup -} mutant lines, isolated as either spontaneous, gamma-induced, or alpha-radiation-induced mutants, indicated that 86-95% of these were complete vector deletions. The integrated gpt vector was localized by in situ hybridization to the q arm of chromosome 5 in close proximity to the interstitial ttelomeresequences near the pericentric region of this chromosome. One to three kilobases of sequences adjacent to the gpt integration site were clones and analyzed. Both the right and left integration sites contain sequences that hybridize to a pantelomere probe, suggesting that the vector has acquired telomeric repeats at its ends. The radio-sensitivity of the gpt locus may be due to these telomere repeats, as interstitial telomeres have been reported to be radiation-sensitive fragile sites. The gpt locus in the T510 line affords a unique resource to test this hypothesis.

  15. Genetic markers on chromosome 7.

    PubMed Central

    Tsui, L C

    1988-01-01

    Chromosome 7 is frequently associated with chromosome aberrations, rearrangements, and deletions. It also contains many important genes, gene families, and disease loci. This brief review attempts to summarise these and other interesting aspects of chromosome 7. With the rapid accumulation of cloned genes and polymorphic DNA fragments, this chromosome has become an excellent substrate for molecular genetic studies. PMID:3290488

  16. Incidence of Chromosome Disorders

    PubMed Central

    Valentine, G. H.

    1979-01-01

    A minority of conceptions result in live births. Of recognized conceptions, 15% result in spontaneous abortions, up to 60% of which are due to chromosome abnormalities. The incidence of the different disorders is given. Of live births, one in 200 suffers a chromosome abnormality. The common abnormalities are described with their incidence. The effect of maternal age on this incidence is pronounced, but even so must be kept in proportion for counselling purposes.

  17. 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.

  18. Validation of a major quantitative trait locus associated with host response to experimental infection with Porcine Reproductive and Respiratory Syndrome virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious diseases are costly to the swine industry and porcine reproductive and respiratory syndrome virus (PRRSV) is the most devastating. In earlier work, a quantitative trait locus associated with resistance/susceptibility to PRRSV was identified on Sus scrofa chromosome 4 (SSC4) using ~560 exp...

  19. 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

  20. 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.

  1. High-density genetic maps for loci involved in nuclear male sterility (NMS1) and sporophytic self-incompatibility (S-locus) in chicory (Cichorium intybus L., Asteraceae).

    PubMed

    Gonthier, Lucy; Blassiau, Christelle; Mörchen, Monika; Cadalen, Thierry; Poiret, Matthieu; Hendriks, Theo; Quillet, Marie-Christine

    2013-08-01

    High-density genetic maps were constructed for loci involved in nuclear male sterility (NMS1-locus) and sporophytic self-incompatibility (S-locus) in chicory (Cichorium intybus L.). The mapping population consisted of 389 F1' individuals derived from a cross between two plants, K28 (male-sterile) and K59 (pollen-fertile), both heterozygous at the S-locus. This F1' mapping population segregated for both male sterility (MS) and strong self-incompatibility (SI) phenotypes. Phenotyping F1' individuals for MS allowed us to map the NMS1-locus to linkage group (LG) 5, while controlled diallel and factorial crosses to identify compatible/incompatible phenotypes mapped the S-locus to LG2. To increase the density of markers around these loci, bulked segregant analysis was used. Bulks and parental plants K28 and K59 were screened using amplified fragment length polymorphism (AFLP) analysis, with a complete set of 256 primer combinations of EcoRI-ANN and MseI-CNN. A total of 31,000 fragments were generated, of which 2,350 showed polymorphism between K59 and K28. Thirteen AFLP markers were identified close to the NMS1-locus and six in the vicinity of the S-locus. From these AFLP markers, eight were transformed into sequence-characterized amplified region (SCAR) markers and of these five showed co-dominant polymorphism. The chromosomal regions containing the NMS1-locus and the S-locus were each confined to a region of 0.8 cM. In addition, we mapped genes encoding proteins similar to S-receptor kinase, the female determinant of sporophytic SI in the Brasicaceae, and also markers in the vicinity of the putative S-locus of sunflower, but none of these genes or markers mapped close to the chicory S-locus. PMID:23689744

  2. Chromosomal Abnormalities and Schizophrenia

    PubMed Central

    BASSETT, ANNE S.; CHOW, EVA W.C.; WEKSBERG, ROSANNA

    2011-01-01

    Schizophrenia is a common and serious psychiatric illness with strong evidence for genetic causation, but no specific loci yet identified. Chromosomal abnormalities associated with schizophrenia may help to understand the genetic complexity of the illness. This paper reviews the evidence for associations between chromosomal abnormalities and schizophrenia and related disorders. The results indicate that 22q11.2 microdeletions detected by fluorescence in-situ hybridization (FISH) are significantly associated with schizophrenia. Sex chromosome abnormalities seem to be increased in schizophrenia but insufficient data are available to indicate whether schizophrenia or related disorders are increased in patients with sex chromosome aneuploidies. Other reports of chromosomal abnormalities associated with schizophrenia have the potential to be important adjuncts to linkage studies in gene localization. Advances in molecular cytogenetic techniques (i.e., FISH) have produced significant increases in rates of identified abnormalities in schizophrenia, particularly in patients with very early age at onset, learning difficulties or mental retardation, or dysmorphic features. The results emphasize the importance of considering behavioral phenotypes, including adult onset psychiatric illnesses, in genetic syndromes and the need for clinicians to actively consider identifying chromosomal abnormalities and genetic syndromes in selected psychiatric patients. PMID:10813803

  3. 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.

  4. Analysis and in situ mapping of the Adh locus in species of the willistoni group of Drosophila.

    PubMed

    Rohde, C; Abdelhay, E; Pinto Júnior, H; Schrank, A; Valente, V L

    1995-01-01

    The Adh locus was mapped by in situ hybridization with the heterologous biotinylated probe SAC-PAT to the salivary chromosomes of seven species of the willistoni group of Drosophila. Hybridization signals were obtained mainly at a single site to the right arm of chromosome II in six species, but in Drosophila nebulosa two sites hybridized with the same consistency. Southern blot analysis Eco RI-digested genomic DNA of the seven species revealed high molecular weight bands shared by three species, plus the appropriately sized fragment expected, suggesting the presence of Adh pseudogenes in those species. PMID:7671636

  5. Inositol Mutants of SACCHAROMYCES CEREVISIAE: Mapping the ino1 Locus and Characterizing Alleles of the ino1, ino2 and ino4 Loci

    PubMed Central

    Donahue, Thomas F.; Henry, Susan A.

    1981-01-01

    An extensive genetic analysis of inositol auxotrophic mutants of yeast is reported. The analysis includes newly isolated mutants, as well as those previously reported (Culbertson and Henry 1975). Approximately 70% of all inositol auxotrophs isolated are shown to be alleles of the ino1 locus, the structural gene for inositol-1-phosphate synthase, the major enzyme involved in inositol biosynthesis. Alleles of two other loci, ino2 and ino4, comprise 9% of total mutants, with the remainder representing unique loci or complementation groups. The ino1 locus was mapped by trisomic analysis with an n + 1 disomic strain constructed with complementing alleles at this locus. The ino1 locus is shown to be located between ura2 (11.1 cm) and cdc6 (21.8 cm) on chromosome X. An extended map of chromosome X of yeast is presented. Unlike most yeast loci, but similar to the his1 locus, the ino1 locus lacks allelic representatives that are suppressible by known suppressors. This finding suggests that premature termination of translation of the ino1 gene product may be incompatible with cell viability. PMID:17249096

  6. 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

  7. 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.

  8. A Z-linked sterility locus causes sexual abstinence in hybrid females and facilitates speciation in Spodoptera frugiperda.

    PubMed

    Kost, Silvia; Heckel, David G; Yoshido, Atsuo; Marec, František; Groot, Astrid T

    2016-06-01

    In the fall armyworm, Spodoptera frugiperda (Lepidoptera, Noctuidae), two sympatric strains have been recognized that have been termed corn strain (C) and rice strain (R), referring to their most common host plants. Both strains are reproductively isolated via a distinct prezygotic barrier as well as via an intriguing postzygotic phenomenon: when R females have mated with C males, the resulting RC hybrid females exhibit dramatically reduced fertility independent of their mating partner. Here, we demonstrate that the reduced fertility is caused by the fact that these females refrain from mating, that is, females are behaviorally sterile. We identified a Z-chromosomally linked sterility locus that is most likely incompatible with yet to be identified autosomal (or cytoplasmic) factors, leading to the observed sexual abstinence. Within-chromosome mapping revealed the sterility locus to be located in an area of strongly reduced interstrain recombination. PMID:27149933

  9. Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2)

    SciTech Connect

    Huebner, K.; Kastury, K.; Druck, T.

    1994-07-15

    Abnormalities due to chromosomal aberration or point mutation in gene products of growth factor receptors or in ras gene products, which lie on the same signaling pathway, can cause disease in animals and humans. Thus, it can be important to determine chromosomal map positions of genes encoding {open_quotes}adapter{close_quotes} proteins, which are involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as ras, because adaptor protein genes could also, logically, serve as targets of mutation, rearrangement, or other aberration in disease. Therefore, DNAs from panels of rodent-human hybrids carrying defined complements of human chromosomes were assayed for the presence of the cognate genes for NCK, SHC, and GRB2, three SH2 or SH2/SH3 (Src homology 2 and 3) domain-containing adapter proteins. Additionally, NCK and SHC genes were more narrowly localized by chromosomal in situ hybridization. The NCK locus is at chromosome region 3q21, a region involved in neoplasia-associated changes; the SHC cognate locus, SHC1, is at 1q21, and the GRB2 locus is at 17q22-qter telomeric to the HOXB and NGFR loci. Both SHC1 and GRB2 are in chromosome regions that may be duplicated in some tumor types. 41 refs., 4 figs.

  10. Functional and genetic analysis of haplotypic sequence variation at the nicastrin genomic locus

    PubMed Central

    Hamilton, Gillian; Killick, Richard; Lambert, Jean-Charles; Amouyel, Philippe; Carrasquillo, Minerva M.; Pankratz, V. Shane; Graff-Radford, Neill R.; Dickson, Dennis W.; Petersen, Ronald C.; Younkin, Steven G.; Powell, John F.; Wade-Martins, Richard

    2013-01-01

    Nicastrin (NCSTN) is a component of the γ-secretase complex and therefore potentially a candidate risk gene for Alzheimer's disease. Here, we have developed a novel functional genomics methodology to express common locus haplotypes to assess functional differences. DNA recombination was used to engineer 5 bacterial artificial chromosomes (BACs) to each express a different haplotype of the NCSTN locus. Each NCSTN-BAC was delivered to knockout nicastrin (Ncstn−/−) cells and clonal NCSTN-BAC+/Ncstn−/− cell lines were created for functional analyses. We showed that all NCSTN-BAC haplotypes expressed nicastrin protein and rescued γ-secretase activity and amyloid beta (Aβ) production in NCSTN-BAC+/Ncstn−/− lines. We then showed that genetic variation at the NCSTN locus affected alternative splicing in human postmortem brain tissue. However, there was no robust functional difference between clonal cell lines rescued by each of the 5 different haplotypes. Finally, there was no statistically significant association of NCSTN with disease risk in the 4 cohorts. We therefore conclude that it is unlikely that common variation at the NCSTN locus is a risk factor for Alzheimer's disease. PMID:22405046

  11. Mapping, phylogenetic and expression analysis of the RNase (RNase A) locus in cattle.

    PubMed

    Wheeler, Thomas T; Maqbool, Nauman J; Gupta, Sandeep K

    2012-06-01

    The mammalian secreted ribonucleases (RNases) comprise a large family of structurally related proteins displaying considerable sequence variation, and have been used in evolutionary studies. RNase 1 (RNase A) has been assumed to play a role in digestion, while other members have been suggested to contribute to host defence. Using the recently assembled bovine genome sequence, we characterised the complete repertoire of genes present in the RNaseA family locus in cattle, and compared this with the equivalent locus in the human and mouse genomes. Several additions and corrections to the earlier analysis of the RNase locus in the mouse genome are presented. The bovine locus encodes 19 RNases, of which only six have unambiguous equivalent genes in the other two species. Chromosomal mapping and phylogenetic analysis indicate that a number of distinct gene duplication events have occurred in the cattle lineage since divergence from the human and mouse lineages. Substitution analysis suggests that some of these duplicated genes are under evolutionary pressure for purifying selection and may therefore be important to the physiology of cattle. Expression analysis revealed that individual RNases have a wide pattern of expression, including diverse mucosal epithelia and immune-related cells and tissues. These data clarify the full repertoire of bovine RNases and their relationships to those in humans and mice. They also suggest that RNase gene duplication within the bovine lineage accompanied by altered tissue-specific expression has contributed a survival advantage. PMID:22562705

  12. Association of Disomic Chromosome Loss with Ems-Induced Conversion in Yeast

    PubMed Central

    Campbell, Douglas

    1980-01-01

    Experimental tests with the yeast Saccharomyces cerevisiae of a previously proposed model suggesting a causal relationship between disomic chromosome loss (n + 1 → n) and centromere-adjacent mitotic gene conversion were performed. Disomic haploid cells heteroallelic at two loci on the left arm of chromosome III were exposed to ethyl methanesulfonate (EMS) under nonlethal conditions; EMS-induced prototrophic gene convertants were selected and tested for coincident chromosome loss. The principal results are: (1) The frequency of chromosome loss among EMS-induced gene convertants selected to arise near the centromere is markedly enhanced over basal levels and remains constant, independent of EMS exposure. There is little such enhancement among EMS-induced convertants selected to arise far from the centromere. (2) Chromosome loss is almost completely associated with induced conversion of the centromere-proximal allele at the centromere-adjacent heteroallelic locus. This result is identical to (and confirms) results found previously for spontaneous loss-associated conversion. (3) The conversion polarity at the centromere-adjacent locus among unselected (nonloss-associated) induced or spontaneous mitotic convertants is identical to that among meiotic convertants and markedly favors the contromere-distal allele. These findings are wholly consistent with, and strengthen, the hypothesis that structural involvement of centromeric regions in nearby recombinational events may interfere with proper segregational function and lead to mitotic chromosome loss. PMID:7021313

  13. Variance-component analysis of obesity in type 2 diabetes confirms loci on chromosomes 1q and 11q.

    PubMed

    van Tilburg, Jonathan H O; Sandkuijl, Lodewijk A; Strengman, Eric; Pearson, Peter L; van Haeften, Timon W; Wijmenga, Cisca

    2003-11-01

    To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome-wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of approximately 75% covering all 22 autosomes. Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores > or =1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine-mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. Our study to determine linkage for BMI confirms the presence of quantitative trait loci influencing obesity in subjects with type 2 diabetes on chromosomes 1q31-q42 and 11q14-q24. PMID:14627748

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

    SciTech Connect

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

    2003-06-23

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

  15. Improvement of high-resolution fluorescence in situ hybridisation mapping on chromosomes of Brassica oleracea var. capitata.

    PubMed

    Yang, K; Zhang, Y; Converse, R; Lv, J; Shi, M; Zhang, H; Zhu, L

    2016-03-01

    The low resolution of chromosome-based Fluorescence in situ hybridisation (FISH) mapping is primarily due to the structure of the plant cell wall and cytoplasm and the compactness of regular chromosomes, which represent a significant obstacle to FISH. In order to improve spatial resolution and signal detection sensitivity, we provide a reproducible method to generate high-quality extended chromosomes that are ~13 times as long as their pachytene counterparts. We demonstrate that proteinase K used in this procedure is crucial for stretching pachytene chromosomes of Brassica oleracea in the context of a modified Carnoy's II fixative (6:1:3, ethanol:chloroform:acetic acid). The quality of super-stretched chromosomes was assessed in several FISH experiments. FISH signals from both repetitive 5S rDNA and single-copy ARC1 on super-stretched chromosomes are brighter than those on other different types of chromosome due to enhanced accessibility to targets on stretched pachytene chromosomes. In conclusion, the resulting extended chromosomes are suitable for FISH mapping for repetitive DNA sequences and the localisation of a single-copy locus, and FISH performed on super-stretched chromosomes can achieve significantly higher sensitivity and spatial resolution than other chromosome-based FISH mapping techniques. PMID:26312399

  16. 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

  17. Fine mapping of the nail-patella syndrome locus at 9q34.

    PubMed Central

    McIntosh, I; Clough, M V; Schäffer, A A; Puffenberger, E G; Horton, V K; Peters, K; Abbott, M H; Roig, C M; Cutone, S; Ozelius, L; Kwiatkowski, D J; Pyeritz, R E; Brown, L J; Pauli, R M; McCormick, M K; Francomano, C A

    1997-01-01

    Nail-patella syndrome (NPS), or onychoosteodysplasia, is an autosomal dominant, pleiotropic disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns, and nephropathy. Previous studies have demonstrated linkage of the nail-patella locus to the ABO and adenylate kinase loci on human chromosome 9q34. As a first step toward isolating the NPS gene, we present linkage analysis with 13 polymorphic markers in five families with a total of 69 affected persons. Two-point linkage analysis with the program MLINK showed tight linkage of NPS and the anonymous markers D9S112 (LOD = 27.0; theta = .00) and D9S315 (LOD = 22.0; theta = .00). Informative recombination events place the NPS locus within a 1-2-cM interval between D9S60 and the adenylate kinase gene (AK1). PMID:8981956

  18. 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.

  19. 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.

  20. 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.

  1. Localization of a bidirectional DNA replication origin in the native locus and in episomally amplified murine adenosine deaminase loci.

    PubMed Central

    Carroll, S M; DeRose, M L; Kolman, J L; Nonet, G H; Kelly, R E; Wahl, G M

    1993-01-01

    Gene amplification is frequently mediated by the initial production of acentric, autonomously replicating extrachromosomal elements. The 4,000 extrachromosomal copies of the mouse adenosine deaminase (ADA) amplicon in B-1/50 cells initiate their replication remarkably synchronously in early S phase and at approximately the same time as the single-copy chromosomal locus from which they were derived. The abundance of ADA sequences and favorable replication timing characteristics in this system led us to determine whether DNA replication initiates in ADA episomes within a preferred region and whether this region is the same as that used at the corresponding chromosomal locus prior to amplification. This study reports the detection and localization of a discrete set of DNA fragments in the ADA amplicon which label soon after release of synchronized B-1/50 cells into S phase. A switch in template strand complementarity of Okazaki fragments, indicative of the initiation of bidirectional DNA replication, was found to lie within the same region. This putative replication origin is located approximately 28.5 kbp upstream of the 5' end of the ADA gene. The same region initiated DNA replication in the single-copy ADA locus of the parental cells. These analyses provide the first evidence that the replication of episomal intermediates involved in gene amplification initiates within a preferred region and that the same region is used to initiate DNA synthesis within the native locus. Images PMID:8474455

  2. Chromosomes of kinetoplastida.

    PubMed Central

    Van der Ploeg, L H; Cornelissen, A W; Barry, J D; Borst, P

    1984-01-01

    We have compared chromosome-sized DNA molecules (molecular karyotypes) of five genera (nine species) of kinetoplastida after cell lysis and deproteinization of DNA in agarose blocks and size fractionation of the intact DNA molecules by pulsed field gradient (PFG) gel electrophoresis. With the possible exception of Trypanosoma vivax and Crithidia fasciculata, all species have at least 20 chromosomes. There are large differences between species in molecular karyotype and in the chromosomal distribution of the genes for alpha- and beta-tubulin, rRNA and the common mini-exon sequence of kinetoplastid mRNAs. In all cases, the rRNA genes are in DNA that is larger than 500 kb. Whereas T. brucei has approximately 100 mini-chromosomes of 50-150 kb, only few are found in T. equiperdum; T. vivax has no DNA smaller than 2000 kb. As all three species exhibit antigenic variation, small chromosomes with telomeric variant surface glycoprotein genes cannot be vital to the mechanism of antigenic variation. The apparent plasticity of kinetoplastid genome composition makes PFG gel electrophoresis a potentially useful tool for taxonomic studies. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:6526012

  3. 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.

  4. 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

  5. Coat colour in dogs: identification of the Merle locus in the Australian shepherd breed

    PubMed Central

    Hédan, Benoit; Corre, Sébastien; Hitte, Christophe; Dréano, Stéphane; Vilboux, Thierry; Derrien, Thomas; Denis, Bernard; Galibert, Francis; Galibert, Marie-Dominique; André, Catherine

    2006-01-01

    Background Coat colours in canines have many natural phenotypic variants. Some of the genes and alleles involved also cause genetic developmental defects, which are also observed in humans and mice. We studied the genetic bases of the merle phenotype in dogs to shed light on the pigmentation mechanisms and to identify genes involved in these complex pathways. The merle phenotype includes a lack of eumelanic pigmentation and developmental defects, hearing impairments and microphthalmia. It is similar to that observed in microphthalmia mouse mutants. Results Taking advantage of the dog as a powerful genetic model and using recently available genomic resources, we investigated the segregation of the merle phenotype in a five-generation pedigree, comprising 96 sampled Australian shepherd dogs. Genetic linkage analysis allowed us to identify a locus for the merle phenotype, spanning 5.5 megabases, at the centromeric tip of canine chromosome 10 (CFA10). This locus was supported by a Lod score of 15.65 at a recombination fraction θ = 0. Linkage analysis in three other breeds revealed that the same region is linked to the merle phenotype. This region, which is orthologous to human chromosome 12 (HSA12 q13-q14), belongs to a conserved ordered segment in the human and mouse genome and comprises several genes potentially involved in pigmentation and development. Conclusion This study has identified the locus for the merle coat colour in dogs to be at the centromeric end of CFA10. Genetic studies on other breeds segregating the merle phenotype should allow the locus to be defined more accurately with the aim of identifying the gene. This work shows the power of the canine system to search for the genetic bases of mammalian pigmentation and developmental pathways. PMID:16504149

  6. 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.

  7. Plant Sex Chromosomes.

    PubMed

    Charlesworth, Deborah

    2016-04-29

    Although individuals in most flowering plant species, and in many haploid plants, have both sex functions, dioecious species-in which individuals have either male or female functions only-are scattered across many taxonomic groups, and many species have genetic sex determination. Among these, some have visibly heteromorphic sex chromosomes, and molecular genetic studies are starting to uncover sex-linked markers in others, showing that they too have fully sex-linked regions that are either too small or are located in chromosomes that are too small to be cytologically detectable from lack of pairing, lack of visible crossovers, or accumulation of heterochromatin. Detailed study is revealing that, like animal sex chromosomes, plant sex-linked regions show evidence for accumulation of repetitive sequences and genetic degeneration. Estimating when recombination stopped confirms the view that many plants have young sex-linked regions, making plants of great interest for studying the timescale of these changes. PMID:26653795

  8. Sex chromosome drive.

    PubMed

    Helleu, Quentin; Gérard, Pierre R; Montchamp-Moreau, Catherine

    2015-02-01

    Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are overrepresented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species. PMID:25524548

  9. Chromosomal locations of three Bacillus subtilis din genes

    SciTech Connect

    Gillespie, K.; Yasbin, R.E.

    1987-07-01

    Previously isolated DNA damage-inducible (din) genes of Bacillus subtilis have been mapped on the bacterial chromosome by bacteriophage PBS1-mediated transduction. The din genes have been localized to three positions on the B. subtilis map. dinA cotransduction with the hisA locus was 80%, while dinC cotransduction with this marker was about 56%. dinB is unlinked to hisA, but its cotransduction with the dal-1 and purB loci was 84 and 22%, respectively.

  10. 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.

  11. Chromosomes and clinical anatomy.

    PubMed

    Gardner, Robert James McKinlay

    2016-07-01

    Chromosome abnormalities may cast light on the nature of mechanisms whereby normal anatomy evolves, and abnormal anatomy arises. Correlating genotype to phenotype is an exercise in which the geneticist and the anatomist can collaborate. The increasing power of the new genetic methodologies is enabling an increasing precision in the delineation of chromosome imbalances, even to the nucleotide level; but the classical skills of careful observation and recording remain as crucial as they always have been. Clin. Anat. 29:540-546, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990310