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Sample records for 8p21 mapped locus

  1. [Mapping of a deletion interval on 8p21-22 in prostate cancer by gene dosage PCR].

    PubMed

    Schmidt, H; Semjonow, A; Csiszar, K; Korsching, E; Brandt, B; Eltze, E

    2007-01-01

    Various microsatellite and CGH studies in prostate cancer identify deletions on the short arm of chromosome 8 especially at band 8p21-22 searching for unknown putative tumor suppressor genes. By means of microsatellite markers several candidate genes were detected which may play different roles in early prostate cancer progression. We established a quantitative gene dosage PCR based on the real time PCR method serving the purpose of genomic fine mapping. Therefore we used 10 Assays-on Demand (ABI) for the detection of deletions located between and nearby the microsatellite markers D8S258 and NEFL spanning a genomic region of approximate 7 mbp. Comparative immunohistochemical analysis from tissue micro arrays (TMA) of 1122 independent cases followed. We were able to detect three clearly separated deletion intervals on 8p21-22. One on LZTS1, second on NEFL and third a deletion hot spot on LOXL2, which was affected in 72% of all investigated cases. Our comparative immunohistochemical TMA based studies demonstrate that LOXL2 is nearly lost in most prostate cancer tissues. LOXL2 catalyze the crosslinking of collagen and elastin in the extracellular matrix and it has been assumed that it is involved in tumor suppression and cell adhesion. LOXL2 is frequently expressed in proliferating tissues and shows a high expression in benign prostate tissue too. In prostate cancer the expression is positive correlated with the MIB1-score.

  2. Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese

    PubMed Central

    Li, Yuanfeng; Si, Lanlan; Zhai, Yun; Hu, Yanling; Hu, Zhibin; Bei, Jin-Xin; Xie, Bobo; Ren, Qian; Cao, Pengbo; Yang, Fei; Song, Qingfeng; Bao, Zhiyu; Zhang, Haitao; Han, Yuqing; Wang, Zhifu; Chen, Xi; Xia, Xia; Yan, Hongbo; Wang, Rui; Zhang, Ying; Gao, Chengming; Meng, Jinfeng; Tu, Xinyi; Liang, Xinqiang; Cui, Ying; Liu, Ying; Wu, Xiaopan; Li, Zhuo; Wang, Huifen; Li, Zhaoxia; Hu, Bo; He, Minghui; Gao, Zhibo; Xu, Xiaobing; Ji, Hongzan; Yu, Chaohui; Sun, Yi; Xing, Baocai; Yang, Xiaobo; Zhang, Haiying; Tan, Aihua; Wu, Chunlei; Jia, Weihua; Li, Shengping; Zeng, Yi-Xin; Shen, Hongbing; He, Fuchu; Mo, Zengnan; Zhang, Hongxing; Zhou, Gangqiao

    2016-01-01

    Hepatitis B virus (HBV) infection is a common infectious disease. Here we perform a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci involved in persistent HBV infection. GWAS scan is performed in 1,251 persistently HBV infected subjects (PIs, cases) and 1,057 spontaneously recovered subjects (SRs, controls), followed by replications in four independent populations totally consisting of 3,905 PIs and 3,356 SRs. We identify a novel locus at 8p21.3 (index rs7000921, odds ratio=0.78, P=3.2 × 10−12). Furthermore, we identify significant expression quantitative trait locus associations for INTS10 gene at 8p21.3. We demonstrate that INST10 suppresses HBV replication via IRF3 in liver cells. In clinical plasma samples, we confirm that INST10 levels are significantly decreased in PIs compared with SRs, and negatively correlated with the HBV load. These findings highlight a novel antiviral gene INTS10 at 8p21.3 in the clearance of HBV infection. PMID:27244555

  3. Mapping of panda plumage color locus on the microsatellite linkage map of the Japanese quail

    PubMed Central

    Miwa, Mitsuru; Inoue-Murayama, Miho; Kobayashi, Naoki; Kayang, Boniface Baboreka; Mizutani, Makoto; Takahashi, Hideaki; Ito, Shin'ichi

    2006-01-01

    Background Panda (s) is an autosomal recessive mutation, which displays overall white plumage color with spots of wild-type plumage in the Japanese quail (Coturnix japonica). In a previous study, the s locus was included in the same linkage group as serum albumin (Alb) and vitamin-D binding protein (GC) which are mapped on chicken (Gallus gallus) chromosome 4 (GGA4). In this study, we mapped the s locus on the microsatellite linkage map of the Japanese quail by linkage analysis. Results Segregation data on the s locus were obtained from three-generation families (n = 106). Two microsatellite markers derived from the Japanese quail chromosome 4 (CJA04) and three microsatellite markers derived from GGA4 were genotyped in the three-generation families. We mapped the s locus between GUJ0026 and ABR0544 on CJA04. By comparative mapping with chicken, this locus was mapped between 10.0 Mb and 14.5 Mb region on GGA4. In this region, the endothelin receptor B subtype 2 gene (EDNRB2), an avian-specific paralog of the mammalian endothelin receptor B gene (EDNRB), is located. Because EDNRB is responsible for aganglionic megacolon and spot coat color in mouse, rat and equine, EDNRB2 is suggested to be a candidate gene for the s locus. Conclusion The s locus and the five microsatellite markers were mapped on CJA04 of the Japanese quail. EDNRB2 was suggested to be a candidate gene for the s locus. PMID:16405738

  4. A novel 6.14 Mb duplication of chromosome 8p21 in a patient with autism and self mutilation.

    PubMed

    Ozgen, Heval M; Staal, Wouter G; Barber, John C; de Jonge, Maretha V; Eleveld, Marc J; Beemer, Frits A; Hochstenbach, Ron; Poot, Martin

    2009-02-01

    Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with a strong genetic etiology. Cytogenetic abnormalities have been detected in 5-10% of the patients with autism. In this study, we present the clinical, cytogenetic and array-comparative genomic hybridization (array-CGH) evaluation of a 13-year-old male with severe developmental delay, facial dysmorphic features, autism and self mutilation. The patient was found to carry a de novo duplication of chromosome region 8p21 of minimally 6.14 and maximally 6.58 Mb as ascertained by bacterial artificial chromosome (BAC)-based array-CGH. Hitherto, only a few patients with autism with cytogenetically visible duplications involving the chromosome 8p21 region have been described, but the extent of these duplications has not been determined at the molecular level. This represents the smallest rearrangement of chromosomal region 8p21 as yet found in a patient with autism. For 11 of the 36 genes with known functions located within this duplication clear transcription in the brain was found. Of those the STMN4 and DPYSL2 genes are the most likely candidate genes to be involved in neuronal development, and, if altered in gene-dosage, in the autistic phenotype of our patient.

  5. Map-based quantitative trait locus identification.

    PubMed

    Hillel, J

    1997-08-01

    Poultry gene mappers chose microsatellites as the main source of genetic markers for poultry genome mapping, similar to the marker type used for other farm animals, laboratory animals, and humans. Optimal strategies for applying DNA markers in poultry populations are discussed, including the number of markers to be used, genome representation, population structure, choice of markers, population size, statistical stringency for association between markers and quantitative trait loci (QTL), and biological verification of a linkage. It is shown that an efficient strategy should be based on a combination of a low stringent statistical test for the existence of linkage between a marker and QTL and an appropriate genetic test for the discrimination between true and false linkage. The source of the genetic variation to be used is discussed and, as an illustration, three types of resource populations are presented. The informativeness of different matings using various genotypes of the parents are considered and it appears that selection of markers based on the heterozygosity of the sire is the most efficient marker screening approach.

  6. Congenic mapping and sequence analysis of the Renin locus

    PubMed Central

    Flister, Michael J.; Hoffman, Matthew J.; Reddy, Prajwal; Jacob, Howard J.; Moreno, Carol

    2013-01-01

    Renin was the first blood pressure (BP) quantitative trait locus (QTL) mapped by linkage analysis in the rat. Subsequent BP linkage and congenic studies capturing different portions of the renin region have returned conflicting results, suggesting that multiple interdependent BP loci may be residing in the chromosome 13 BP QTL that includes Renin. We used SS-13BN congenic strains to map 2 BP loci in the Renin region (chr13:45.2–49.0 Mb). We identified a 1.1 Mb protective Brown Norway (BN) region around Renin (chr13:46.1–47.2 Mb) that significantly decreased BP by 32 mmHg. The Renin protective BP locus was offset by an adjacent hypertensive locus (chr13:47.2–49.0 Mb) that significantly increased BP by 29 mmHg. Sequence analysis of the protective and hypertensive BP loci revealed 1,433 and 2,063 variants between Dahl salt-sensitive/Mcwi (SS) and BN rats, respectively. To further reduce the list of candidate variants, we re-genotyped an overlapping SS-13SR congenic strain (S/renrr) with a previously reported BP phenotype. Sequence comparison between SS, Dahl R (SR), and BN reduced the number of candidate variants in the 2 BP loci by 42% for further study. Combined with previous studies, these data suggest that at least 4 BP loci reside within the 30 cM chromosome 13 BP QTL that includes Renin. PMID:23460292

  7. Homozygosity mapping of the Werner syndrome locus (WRN)

    SciTech Connect

    Nakura, J.; Miki, T.; Kamino, K.

    1994-10-01

    Werner syndrome (WS) is an autosomal recessive disorder characterized by the early onset of several age-related diseases. The locus for this disease was recently mapped to 8p12. We studied 27 WS kindreds of mixed ethnic origins, 26 of which were consanguineous. In 24 of these families, the affected subject was given the diagnosis of {open_quotes}definite{close_quotes} WS and affected subjects in the remaining 3 pedigrees were given the diagnosis of {open_quotes}probable{close_quotes} WS. Affected subjects from each kindred were genotyped for 13 short tandem repeat polymorphic sites. Two-point linkage analysis yielded significant evidence for linkage to D8S137, D8S339, D8S87, PLAT, D8S165, and D8S166. The locus yielding a maximum lod score at the smallest recombination fraction was D8S339, suggesting that this marker is the closest to the WS gene (WRN locus) of those tested. D8S339 gave significant lod scores (Z{sub max}{>=}3.0) for both Japanese and non-Japanese (mostly Caucasian) families, demonstrating that a single locus is responsible for WS in both groups. Multipoint analysis of these markers yielded a maximum lod score of 17.05 at a distance of approximately 0.6 cM from D8S339. The combined evidence from 2-point analysis, multipoint analysis, and analysis of regions of homozygosity in subjects from inbred pedigrees indicates that the WRN locus is between D8S131 and D8S87, in an 8.3-cM interval containing D8S339. 32 refs., 1 fig., 5 tabs.

  8. Haplotype mapping of the bronchiolitis susceptibility locus near IL8.

    PubMed

    Hull, Jeremy; Rowlands, Kate; Lockhart, Elizabeth; Sharland, Mike; Moore, Catrin; Hanchard, Neil; Kwiatkowski, Dominic P

    2004-02-01

    Susceptibility to viral bronchiolitis, the commonest cause of infant admissions to hospital in the industrialised world, is associated with polymorphism at the IL8 locus. Here we map the genomic boundaries of the disease association by case-control analysis and TDT in 580 affected UK infants. Markers for association mapping were chosen after determining patterns of linkage disequilibrium across the surrounding region of chromosome 4q, a 550-kb segment containing nine genes, extending from AFP to PPBP. The region has three major clusters of high linkage disequilibrium and is notable for its low haplotypic diversity. We exclude adjacent chemokine genes as the cause of the association, and identify a disease-associated haplotype that spans a 250-kb region from AFM to IL8. In between these two genes there is only one structural feature of interest, a novel gene RASSF6, which is predicted to encode a Ras effector protein.

  9. Empirical Bayesian elastic net for multiple quantitative trait locus mapping

    PubMed Central

    Huang, A; Xu, S; Cai, X

    2015-01-01

    In multiple quantitative trait locus (QTL) mapping, a high-dimensional sparse regression model is usually employed to account for possible multiple linked QTLs. The QTL model may include closely linked and thus highly correlated genetic markers, especially when high-density marker maps are used in QTL mapping because of the advancement in sequencing technology. Although existing algorithms, such as Lasso, empirical Bayesian Lasso (EBlasso) and elastic net (EN) are available to infer such QTL models, more powerful methods are highly desirable to detect more QTLs in the presence of correlated QTLs. We developed a novel empirical Bayesian EN (EBEN) algorithm for multiple QTL mapping that inherits the efficiency of our previously developed EBlasso algorithm. Simulation results demonstrated that EBEN provided higher power of detection and almost the same false discovery rate compared with EN and EBlasso. Particularly, EBEN can identify correlated QTLs that the other two algorithms may fail to identify. When analyzing a real dataset, EBEN detected more effects than EN and EBlasso. EBEN provides a useful tool for inferring high-dimensional sparse model in multiple QTL mapping and other applications. An R software package ‘EBEN' implementing the EBEN algorithm is available on the Comprehensive R Archive Network (CRAN). PMID:25204301

  10. The locus for bovine dilated cardiomyopathy maps to chromosome 18.

    PubMed

    Guziewicz, K E; Owczarek-Lipska, M; Küffer, J; Schelling, C; Tontis, A; Denis, C; Eggen, A; Leeb, T; Dolf, G; Braunschweig, M H

    2007-06-01

    Bovine dilated cardiomyopathy (BDCMP) is a severe and terminal disease of the heart muscle observed in Holstein-Friesian cattle over the last 30 years. There is strong evidence for an autosomal recessive mode of inheritance for BDCMP. The objective of this study was to genetically map BDCMP, with the ultimate goal of identifying the causative mutation. A whole-genome scan using 199 microsatellite markers and one SNP revealed an assignment of BDCMP to BTA18. Fine-mapping on BTA18 refined the candidate region to the MSBDCMP06-BMS2785 interval. The interval containing the BDCMP locus was confirmed by multipoint linkage analysis using the software loki. The interval is about 6.7 Mb on the bovine genome sequence (Btau 3.1). The corresponding region of HSA19 is very gene-rich and contains roughly 200 genes. Although telomeric of the marker interval, TNNI3 is a possible positional and a functional candidate for BDCMP given its involvement in a human form of dilated cardiomyopathy. Sequence analysis of TNNI3 in cattle revealed no mutation in the coding sequence, but there was a G-to-A transition in intron 6 (AJ842179:c.378+315G>A). The analysis of this SNP using the study's BDCMP pedigree did not conclusively exclude TNNI3 as a candidate gene for BDCMP. Considering the high density of genes on the homologous region of HSA19, further refinement of the interval on BTA18 containing the BDCMP locus is needed.

  11. Multipoint mapping of the central core disease locus

    SciTech Connect

    Schwemmle, S.; Wolff, K.; Grimm, T.; Mueller, C.R. ); Palmucci, L.M. ); Lehmann-Horn, F. ); Huebner, Ch. ); Hauser, E. ); Iles, D.E. ); MacLennan, D.H. )

    1993-07-01

    A linkage analysis with 12 DNA markers from proximal 19q was performed in eight families with central core disease (CCO). Two-point analysis gave a peak lod score of Z = 4.95 at [theta] = 0.00 for the anonymous marker D19S190 and of Z = 2.53 at [theta] = 0.00 for the ryanodine receptor (RYR1) candidate gene. Multipoint linkage data place the CCO locus at 19q13.1, flanked proximally by D19S191/D19S28 and distally by D19S47. This map location includes the RYR1 gene. The results of the linkage study present no evidence for genetic heterogeneity of CCO. 19 refs., 2 figs., 1 tab.

  12. Mapping of the nadB Locus Adjacent to a Previously Undescribed Purine Locus in Escherichia coli K-12

    PubMed Central

    Tritz, Gerald J.; Matney, Thomas S.; Gholson, Robert K.

    1970-01-01

    It is proposed that all mutants blocked in the de novo pathway of nicotinamide adenine dinucleotide biosynthesis be designated nad rather than nic. It is further suggested that mutants blocked in the pyridine nucleotide cycle be designated pnc. The nadB locus and a previously unidentified pur locus are cotransducible. These two loci have been mapped near minute 49 on the standard genetic map of Escherichia coli. The order of genes in that region is purC-guaB-purG-glyA-pur-nadB-tyrA-pheA. PMID:4315893

  13. Mapping of the nadB locus adjacent to a previously undescribed purine locus in Escherichia coli K-12.

    PubMed

    Tritz, G J; Matney, T S; Gholson, R K

    1970-05-01

    It is proposed that all mutants blocked in the de novo pathway of nicotinamide adenine dinucleotide biosynthesis be designated nad rather than nic. It is further suggested that mutants blocked in the pyridine nucleotide cycle be designated pnc. The nadB locus and a previously unidentified pur locus are cotransducible. These two loci have been mapped near minute 49 on the standard genetic map of Escherichia coli. The order of genes in that region is purC-guaB-purG-glyA-pur-nadB-tyrA-pheA.

  14. Two-trait-locus linkage analysis: A powerful strategy for mapping complex genetic traits

    SciTech Connect

    Schork, N.J.; Boehnke, M. ); Terwilliger, J.D.; Ott, J. )

    1993-11-01

    Nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not exhibit simple Mendelian transmission. More complex models are required to explain the genetics of these important diseases. In this paper, the authors explore two-trait-locus, two-marker-locus linkage analysis in which two trait loci are mapped simultaneously to separate genetic markers. The authors compare the utility of this approach to standard one-trait-locus, one-marker-locus linkage analysis with and without allowance for heterogeneity. The authors also compare the utility of the two-trait-locus, two-marker-locus analysis to two-trait-locus, one-marker-locus linkage analysis. For common diseases, pedigrees are often bilineal, with disease genes entering via two or more unrelated pedigree members. Since such pedigrees often are avoided in linkage studies, the authors also investigate the relative information content of unilineal and bilineal pedigrees. For the dominant-or-recessive and threshold models that the authors consider, the authors find that two-trait-locus, two-marker-locus linkage analysis can provide substantially more linkage information, as measured by expected maximum lod score, than standard one-trait-locus, one-marker-locus methods, even allowing for heterogeneity, while, for a dominant-or-dominant generating model, one-locus models that allow for heterogeneity extract essentially as much information as the two-trait-locus methods. For these three models, the authors also find that bilineal pedigrees provide sufficient linkage information to warrant their inclusion in such studies. The authors discuss strategies for assessing the significance of the two linkages assumed in two-trait-locus, two-marker-locus models. 37 refs., 1 fig., 4 tabs.

  15. Quantitative trait locus mapping of soybean maturity gene E5

    PubMed Central

    Dissanayaka, Auchithya; Rodriguez, Tito O.; Di, Shaokang; Yan, Fan; Githiri, Stephen M.; Rodas, Felipe Rojas; Abe, Jun; Takahashi, Ryoji

    2016-01-01

    Time to flowering and maturity in soybean is controlled by loci E1 to E5, and E7 to E9. These loci were assigned to molecular linkage groups (MLGs) except for E5. This study was conducted to map the E5 locus using F2 populations expected to segregate for E5. F2 populations were subjected to quantitative trait locus (QTL) analysis for days to flowering (DF) and maturity (DM). In Harosoy-E5 × Clark-e2 population, QTLs for DF and DM were found at a similar position with E2. In Harosoy × Clark-e2E5 population, QTLs for DF and DM were found in MLG D1a and B1, respectively. In Harosoy-E5Dt2 × Clark-e2 population, a QTL for DF was found in MLG B1. Thus, results from these populations were not fully consistent, and no candidate QTL for E5 was found. In Harosoy × PI 80837 population, from which E5 was originally identified, QTLs corresponding to E1 and E3 were found, but none for E5 existed. Harosoy and PI 80837 had the e2-ns allele whereas Harosoy-E5 had the E2-dl allele. The E2-dl allele of Harosoy-E5 may have been generated by outcrossing and may be responsible for the lateness of Harosoy-E5. We conclude that a unique E5 gene may not exist. PMID:27436951

  16. 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.

  17. Mapping of human immunoglobulin heavy chain variable gene segments outside the major IGH locus

    SciTech Connect

    Wintle, R.F.; Cox, D.W. |

    1994-09-01

    Physical mapping of the human immunoglobulin heavy chain gene cluster (IGH) on chromosome 14 has previously shown that the locus includes at least 63 variable region (VH) gene segments. Fifteen VH gene segments are located on six NotI DNA restriction fragments that are not within the mapped region of IGH. We have used human/rodent somatic cell hybrid lines to map these genes segments, as it was previously not proven that they are located in the chromosome 14 IGH locus. Four gene segments map to human chromosome 16 and two to chromosome 15. Apparently, four of the six NotI fragments, representing 11 VH gene segments, are not located within the chromosome 14 IGH locus. In addition, we have demonstrated that a YAC containing a functional human telomere, and mapping to 14qter, is located at the telomeric end of the IGH gene cluster physical map and contains at least four VH gene segments. This YAC is collinear with the existing physical map of genomic DNA. We conclude that our original physical map of IGH represents almost the entire locus on chromosome 14 and that the 11 gene segments newly mapped are not part of the functional IGH locus. 33 refs., 3 figs., 1 tab.

  18. Heterotic trait locus (HTL) mapping identifies intra-locus interactions that underlie reproductive hybrid vigor in Sorghum bicolor.

    PubMed

    Ben-Israel, Imri; Kilian, Benjamin; Nida, Habte; Fridman, Eyal

    2012-01-01

    Identifying intra-locus interactions underlying heterotic variation among whole-genome hybrids is a key to understanding mechanisms of heterosis and exploiting it for crop and livestock improvement. In this study, we present the development and first use of the heterotic trait locus (HTL) mapping approach to associate specific intra-locus interactions with an overdominant heterotic mode of inheritance in a diallel population using Sorghum bicolor as the model. This method combines the advantages of ample genetic diversity and the possibility of studying non-additive inheritance. Furthermore, this design enables dissecting the latter to identify specific intra-locus interactions. We identified three HTLs (3.5% of loci tested) with synergistic intra-locus effects on overdominant grain yield heterosis in 2 years of field trials. These loci account for 19.0% of the heterotic variation, including a significant interaction found between two of them. Moreover, analysis of one of these loci (hDPW4.1) in a consecutive F2 population confirmed a significant 21% increase in grain yield of heterozygous vs. homozygous plants in this locus. Notably, two of the three HTLs for grain yield are in synteny with previously reported overdominant quantitative trait loci for grain yield in maize. A mechanism for the reproductive heterosis found in this study is suggested, in which grain yield increase is achieved by releasing the compensatory tradeoffs between biomass and reproductive output, and between seed number and weight. These results highlight the power of analyzing a diverse set of inbreds and their hybrids for unraveling hitherto unknown allelic interactions mediating heterosis.

  19. Homozygosity mapping of the locus responsible for renal tubular dysplasia of cattle on bovine chromosome 1.

    PubMed

    Ohba, Y; Kitagawa, H; Kitoh, K; Asahina, S; Nishimori, K; Yoneda, K; Kunieda, T; Sasaki, Y

    2000-04-01

    Renal tubular dysplasia is a hereditary disease of Japanese black cattle showing renal failure and growth retardation with an autosomal recessive trait. In the present study, we mapped the locus responsible for the disease (RTD) by linkage analysis with an inbred paternal half-sib pedigree obtained from commercial herds. By analyzing segregation of microsatellite markers in the half-sibs, significant linkage was observed between the RTD locus and markers on bovine Chromosome (Chr) 1 with the highest lod score of 11.4. Homozygosity mapping with the inbred pedigree further defined the localization of the RTD locus in a 4-cM region between microsatellite markers BMS4003 and INRA119. Mapping of the RTD locus on bovine Chr 1 will facilitate cloning and characterization of the gene responsible for this disease.

  20. Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations.

    PubMed

    Kas, K; Voz, M L; Röijer, E; Aström, A K; Meyen, E; Stenman, G; Van de Ven, W J

    1997-02-01

    Pleiomorphic adenoma of the salivary glands is a benign epithelial tumour occurring primarily in the major and minor salivary glands. It is by far the most common type of salivary gland tumour. Microscopically, pleiomorphic adenomas show a marked histological diversity with epithelial, myoepithelial and mesenchymal components in a variety of patterns. In addition to a cytogenetic subgroup with normal karyotypes, pleiomorphic adenomas are characterized by recurrent chromosome rearrangements, particularly reciprocal translocations, with breakpoints at 8q12, 3p21, and 12q13-15, in that order of frequency. The most common abnormality is a reciprocal t(3;8)(p21;q12). We here demonstrate that the t(3;8)(p21;q12) results in promoter swapping between PLAG1, a novel, developmentally regulated zinc finger gene at 8q12, and the constitutively expressed gene for beta-catenin (CTNNB1), a protein interface functioning in the WG/WNT signalling pathway and specification of cell fate during embryogenesis. Fusions occur in the 5'-non-coding regions of both genes, exchanging regulatory control elements while preserving the coding sequences. Due to the t(3;8)(p21;q12), PLAG1 is activated and expression levels of CTNNB1 are reduced. Activation of PLAG1 was also observed in an adenoma with a variant translocation t(8;15)(q12;q14). Our results indicate that PLAG1 activation due to promoter swapping is a crucial event in salivary gland tumourigenesis.

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

    PubMed

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

    2004-01-01

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

  2. 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.

  3. Detailed mapping of a resistance locus against Fusarium wilt in cultivated eggplant (Solanum melongena).

    PubMed

    Miyatake, Koji; Saito, Takeo; Negoro, Satomi; Yamaguchi, Hirotaka; Nunome, Tsukasa; Ohyama, Akio; Fukuoka, Hiroyuki

    2016-02-01

    This is the first report on genetic mapping of a resistance locus against Fusarium wilt caused by the plant pathogen Fusarium oxysporum f. sp. melongenae in cultivated eggplant. Fusarium wilt, caused by the plant pathogen Fusarium oxysporum f. sp. melongenae, is a major soil-borne disease threatening stable production in eggplant (Solanum melongena). Although three eggplant germplasms, LS1934, LS174, and LS2436, are known to be highly resistant to the pathogen, their resistance loci have not been mapped. In this study, we performed quantitative trait locus analyses in F2:3 populations and detected a resistance locus, FM1, at the end of chromosome 2, with two alleles, Fm1(L) and Fm1(E), in the F2 populations LWF2 [LS1934 × WCGR112-8 (susceptible)] and EWF2 [EPL-1 (derived from LS174) × WCGR112-8], respectively. The percentage of phenotypic variance explained by Fm1(L) derived from LS1934 was 75.0% [Logarithm of the odds (LOD) = 29.3], and that explained by Fm1(E) derived from EPL-1 was 92.2% (LOD = 65.8). Using backcrossed inbred lines, we mapped FM1 between two simple sequence repeat markers located ~4.881 cM apart from each other. Comparing the location of the above locus to those of previously reported ones, the resistance locus Rfo-sa1 from an eggplant ally (Solanum aethiopicum gr. Gilo) was mapped very close to FM1, whereas another resistance locus, from LS2436, was mapped to the middle of chromosome 4. This is the first report of mapping of a Fusarium resistance locus in cultivated eggplant. The availability of resistance-linked markers will enable the application of marker-assisted selection to overcome problems posed by self-incompatibility and introduction of negative traits because of linkage drag, and will lead to clear understanding of genetic mechanism of Fusarium resistance.

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

    SciTech Connect

    Phillips, J.C.; Del Bono, E.A.; Pralea, A.M.

    1996-09-01

    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. 31 refs., 1 fig., 3 tabs.

  5. Fine mapping of the chicken congenital loco locus on chromosome 12.

    PubMed

    Okumura, Y; Ohtake, T; Uemoto, Y; Sato, S; Sato, S; Kobayashi, E

    2013-12-01

    Congenital loco in chicks is characterized by an apparent lack of control of the muscles of the neck. This disorder is inherited as a simple Mendelian recessive disease, caused by an autosomal recessive gene, lo. To date, there are no reports on the localization of this gene. The objective of this study was therefore to identify the genomic region of the lo locus. The experimental congenital loco population used here were selected from a Rhode Island Red (RIR) line and consisted of six generations, resulting in 124 chickens. A total of 113 DNA samples from offspring of four generations (G3, G4, G5, and G6) were used for genotyping. At first, genome-wide linkage mapping was performed using 122 microsatellite markers on 22 autosomal chromosomes, and the lo locus was mapped to chromosome 12. We then performed fine mapping in two steps on chromosome 12. First, the lo locus was mapped to the interval between GGA12_5 and GGA12_11 using 13 new polymorphic markers. In the second step, fine mapping was performed by adding new families and 11 additional new polymorphic markers. Linkage mapping and haplotype information enabled the localization of the lo locus to a 1.1-Mb region between GGA12_28 and GGA12_30. Genetic markers between GGA12_28 and GGA12_30 may be used to remove the carriers of congenital loco through this RIR line.

  6. The X-linked F cell production locus: Genetic mapping and role in fetal hemoglobin production

    SciTech Connect

    Chang, Y.C.; Smith, K.D.; Moore, R.D.

    1994-09-01

    Postnatal fetal hemoglobin (Hb F) production is confined to a subset of erythocytes termed F-cells. There is a 10-20 fold variation in F-cell production in sickle cell disease (SCD) and normal individuals. Most of the variation in F-cell production has been attributed to a diallelic (High, Low) X-linked gene, the F-cell production (FCP) locus that we recently mapped to Xp22.2-22.3 (LOD=4.56, theta=0.04). Using multiple regression analysis in 262 Jamaican SCD patients we determined the relative contribution of the FCP locus and other variables previously associated with variation in Hb F level (gender, age, beta-globin haplotypes, number of alpha-globin genes and the FCP locus phenotypes). When the FCP locus is in the regression model, the FCP locus alone accounts for approximately 40% of the variation in Hb F level while the contribution of age, alpha-globin gene number, and beta-globin haplotypes was insignificant. When individuals with High FCP allele are removed from the analysis, the beta globin haplotype now contribute to >10% of the Hb F variation. We conclude that the X-linked FCP locus is the major determinant of all known variables in Hb F production. Using 4 highly polymorphic dinucleotide repeat markers that we identified from cosmids in Xp22.2-22.3, have localized the FCP locus to a 1 Mb minimal candidate region between DXS143 and DXS410.

  7. Mapping genetic determinants of viral traits with FST and quantitative trait locus (QTL) approaches.

    PubMed

    Doumayrou, Juliette; Thébaud, Gaël; Vuillaume, Florence; Peterschmitt, Michel; Urbino, Cica

    2015-10-01

    The genetic determinism of viral traits can generally be dissected using either forward or reverse genetics because the clonal reproduction of viruses does not require the use of approaches based on laboratory crosses. Nevertheless, we hypothesized that recombinant viruses could be analyzed as sexually reproducing organisms, using either a quantitative trait loci (QTL) approach or a locus-by-locus fixation index (FST). Locus-by-locus FST analysis, and four different regressions and interval mapping algorithms of QTL analysis were applied to a phenotypic and genotypic dataset previously obtained from 47 artificial recombinant genomes generated between two begomovirus species. Both approaches assigned the determinant of within-host accumulation-previously identified using standard virology approaches-to a region including the 5׳ end of the replication-associated protein (Rep) gene and the upstream intergenic region. This study provides a proof of principle that QTL and population genetics tools can be extended to characterize the genetic determinants of viral traits.

  8. Exclusion of linkage to chromosomes 14q, 2q37 and 8p21.1-q11.23 in a Serbian family with idiopathic basal ganglia calcification.

    PubMed

    Kostić, Vladimir S; Lukić-Ječmenica, Milica; Novaković, Ivana; Dobričić, Valerija; Brajković, Lela; Krajinović, Maja; Klein, Christine; Pavlović, Aleksandra

    2011-09-01

    In this study we report clinical and imaging data from a multigenerational Serbian family with idiopathic basal ganglia calcification (IBGC) and exclusion of linkage to chromosome 14q, 2q37 and 8p21.1-q11.23. Fourteen out of 18 family members were personally examined and 11 of them were scanned with computed tomography (CT). CT scans revealed existence of symmetrical calcifications in six family members from three generations (four symptomatic and two asymptomatic). Age at onset of clinical symptoms varied between 22.0 and 55.4 years. The main clinical findings included parkinsonism, severe gait disturbances with freezing of gait, and dyskinesia. Hyperechogenicities identified by transcranial sonography corresponded well to the CT images of hyperintense calcifications in the same structures, whereas brain perfusion single photon emission computed tomography demonstrated predominant hypoperfusion in the frontal cortex and the basal ganglia. After exclusion of linkage to known loci, our pedigree with IBGC further demonstrates locus heterogeneity in this disorder. Analysis of clinically affected individuals supports observation that the clinical features of IBGC appear to be varied both within and between families. The age at onset of the clinical symptoms appeared to be decreasing in two observed transmissions, suggestive of possible genetic anticipation.

  9. Homozygosity mapping of the Achromatopsia locus in the Pingelapese.

    PubMed

    Winick, J D; Blundell, M L; Galke, B L; Salam, A A; Leal, S M; Karayiorgou, M

    1999-06-01

    Achromatopsia, or total color blindness (also referred to as "rod monochromacy"), is a severe retinal disorder characterized clinically by an inability to distinguish colors, impaired visual acuity in daylight, photophobia, and nystagmus. Inherited as an autosomal recessive trait, achromatopsia is rare in the general population (1:20,000-1:50,000). Among the Pingelapese people of the Eastern Caroline Islands, however, the disorder occurs at an extremely high frequency, as recounted in Oliver Sacks's popular book The Island of the Colorblind: 4%-10% of this island population have the disorder and approximately 30% carry the gene. This extraordinary enrichment of the disease allele most likely resulted from a sharp reduction in population in the late 18th century, in the aftermath of a typhoon and subsequent geographic and cultural isolation. To obtain insights into the genetic basis of achromatopsia, as well as into the genetic history of this region of Micronesia, a genomewide search for linkage was performed in three Pingelapese kindreds with achromatopsia. A two-step search was used with a DNA pooling strategy, followed by genotyping of individual family members. Genetic markers that displayed a shift toward homozygosity in the affected DNA pool were used to genotype individual members of the kindreds, and an achromatopsia locus was identified on 8q21-q22. A maximal multipoint LOD score of 9.5 was observed with marker D8S1707. Homozygosity was seen for three adjacent markers (D8S275, D8S1119, and D8S1707), whereas recombination was observed with the flanking markers D8S1757 and D8S270, defining the outer boundaries of the disease-gene locus that spans a distance of <6.5cM.

  10. Homozygosity mapping of the Achromatopsia locus in the Pingelapese.

    PubMed Central

    Winick, J D; Blundell, M L; Galke, B L; Salam, A A; Leal, S M; Karayiorgou, M

    1999-01-01

    Achromatopsia, or total color blindness (also referred to as "rod monochromacy"), is a severe retinal disorder characterized clinically by an inability to distinguish colors, impaired visual acuity in daylight, photophobia, and nystagmus. Inherited as an autosomal recessive trait, achromatopsia is rare in the general population (1:20,000-1:50,000). Among the Pingelapese people of the Eastern Caroline Islands, however, the disorder occurs at an extremely high frequency, as recounted in Oliver Sacks's popular book The Island of the Colorblind: 4%-10% of this island population have the disorder and approximately 30% carry the gene. This extraordinary enrichment of the disease allele most likely resulted from a sharp reduction in population in the late 18th century, in the aftermath of a typhoon and subsequent geographic and cultural isolation. To obtain insights into the genetic basis of achromatopsia, as well as into the genetic history of this region of Micronesia, a genomewide search for linkage was performed in three Pingelapese kindreds with achromatopsia. A two-step search was used with a DNA pooling strategy, followed by genotyping of individual family members. Genetic markers that displayed a shift toward homozygosity in the affected DNA pool were used to genotype individual members of the kindreds, and an achromatopsia locus was identified on 8q21-q22. A maximal multipoint LOD score of 9.5 was observed with marker D8S1707. Homozygosity was seen for three adjacent markers (D8S275, D8S1119, and D8S1707), whereas recombination was observed with the flanking markers D8S1757 and D8S270, defining the outer boundaries of the disease-gene locus that spans a distance of <6.5cM. PMID:10330355

  11. A Locus for Autosomal Dominant Hereditary Spastic Ataxia, SAX1, Maps to Chromosome 12p13

    PubMed Central

    Meijer, I. A.; Hand, C. K.; Grewal, K. K.; Stefanelli, M. G.; Ives, E. J.; Rouleau, G. A.

    2002-01-01

    The hereditary spastic ataxias (HSA) are a group of clinically heterogeneous neurodegenerative disorders characterized by lower-limb spasticity and generalized ataxia. HSA was diagnosed in three unrelated autosomal dominant families from Newfoundland, who presented mainly with severe leg spasticity, dysarthria, dysphagia, and ocular-movement abnormalities. A genomewide scan was performed on one family, and linkage to a novel locus for HSA on chromosome 12p13, which contains the as-yet-unidentified gene locus SAX1, was identified. Fine mapping confirmed linkage in the two large families, and the third, smaller family showed LOD scores suggestive of linkage. Haplotype construction by use of 13 polymorphic markers revealed that all three families share a disease haplotype, which key recombinants and overlapping haplotypes refine to ∼5 cM, flanked by markers D12S93 and GATA151H05. SAX1 is the first locus mapped for autosomal dominant HSA. PMID:11774073

  12. Quantitative Trait Locus Mapping Methods for Diversity Outbred Mice

    PubMed Central

    Gatti, Daniel M.; Svenson, Karen L.; Shabalin, Andrey; Wu, Long-Yang; Valdar, William; Simecek, Petr; Goodwin, Neal; Cheng, Riyan; Pomp, Daniel; Palmer, Abraham; Chesler, Elissa J.; Broman, Karl W.; Churchill, Gary A.

    2014-01-01

    Genetic mapping studies in the mouse and other model organisms are used to search for genes underlying complex phenotypes. Traditional genetic mapping studies that employ single-generation crosses have poor mapping resolution and limit discovery to loci that are polymorphic between the two parental strains. Multiparent outbreeding populations address these shortcomings by increasing the density of recombination events and introducing allelic variants from multiple founder strains. However, multiparent crosses present new analytical challenges and require specialized software to take full advantage of these benefits. Each animal in an outbreeding population is genetically unique and must be genotyped using a high-density marker set; regression models for mapping must accommodate multiple founder alleles, and complex breeding designs give rise to polygenic covariance among related animals that must be accounted for in mapping analysis. The Diversity Outbred (DO) mice combine the genetic diversity of eight founder strains in a multigenerational breeding design that has been maintained for >16 generations. The large population size and randomized mating ensure the long-term genetic stability of this population. We present a complete analytical pipeline for genetic mapping in DO mice, including algorithms for probabilistic reconstruction of founder haplotypes from genotyping array intensity data, and mapping methods that accommodate multiple founder haplotypes and account for relatedness among animals. Power analysis suggests that studies with as few as 200 DO mice can detect loci with large effects, but loci that account for <5% of trait variance may require a sample size of up to 1000 animals. The methods described here are implemented in the freely available R package DOQTL. PMID:25237114

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

    USDA-ARS?s Scientific Manuscript database

    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...

  14. Fine mapping of E(kp)-1, a locus associated with silkworm (Bombyx mori) proleg development.

    PubMed

    Xiang, H; Li, M; Yang, F; Guo, Q; Zhan, S; Lin, H; Miao, X; Huang, Y

    2008-05-01

    The silkworm homeotic mutant E(kp) has a pair of rudimentary abdominal legs, called prolegs, in its A2 segment. This phenotype is caused by a single dominant mutation at the E(kp)-1 locus, which was previously mapped to chromosome 6. To explore the possible association of Hox genes with proleg development in the silkworm, a map-based cloning strategy was used to isolate the E(kp)-1 locus. Five E(kp)-1-linked simple sequence repeat markers on chromosome 6 were used to generate a low-resolution map with a total genetic distance of 39.5 cM. Four additional cleaved amplified polymorphic sequence markers were developed based on the initial map. The closest marker to E(kp)-1 was at a genetic distance of 2.7 cM. A high-resolution genetic map was constructed using nine BC1 segregating populations consisting of 2396 individuals. Recombination suppression was observed in the vicinity of E(kp)-1. Four molecular markers were tightly linked to E(kp)-1, and three were clustered with it. These markers were used to screen a BAC library. A single bacterial artificial chromosome (BAC) clone spanning the E(kp)-1 locus was identified, and E(kp)-1 was delimited to a region less than 220 kb long that included the Hox gene abdominal-A and a non-coding locus, iab-4. These results provide essential information for the isolation of this locus, which may shed light on the mechanism of proleg development in the silkworm and possibly in Lepidoptera.

  15. 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

  16. Gene encoding T-cell-activating protein TAP maps to the Ly-6 locus.

    PubMed Central

    Reiser, H; Yeh, E T; Gramm, C F; Benacerraf, B; Rock, K L

    1986-01-01

    Recently we described two murine T-cell membrane proteins, TAP (T-cell-activating protein) and TAPa (TAP-associated protein). Previous experiments suggested that TAP is involved in physiologic T-cell activation. The subject of this report is a genetic analysis of these molecules. TAP and TAPa map to the Ly-6 locus. The relationship of these molecules to other antigens encoded in this locus is examined. Based on tissue distribution, molecular structure, and functional properties, TAP is distinct from any previously described Ly-6 antigen, whereas TAPa is probably identical to the 34-11-3 antigen. TAP and TAPa are coexpressed on all cell types examined so far. Moreover, comparative studies demonstrate a complex developmentally regulated pattern in the expression of molecules encoded in this locus. Images PMID:3010324

  17. A transcriptional map of the PKD1 locus

    SciTech Connect

    Landes, G.; Dackowski, W.; Burn, T.

    1994-09-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a very common inheritable disease with a frequency of approximately 1 per 1000. While the severity of the disease is variable, 8-10% of the cases clinically proress to end-stage renal disease. The predominant cause of ADPKD, the PKD1 gene, is responsible for about 90% of the cases. The PKD1 gene is located on chromosome 16p13.3 and delimited to an {approximately}750 kb interval defined by the distal marker, D16S84, and the proximal marker, 26.6DIS. This chromosomal segment is known to be contained within a GC-rich isochore, abundant in both CpG-islands and genes. Using filters containing a gridded total human P1 library ({approximately}3 genome equivalents), we have cloned the entire interval as a minimal tiling series of 17 clones. Metaphase FISH has confirmed that each of the clones is solely derived from chromosome 16p13.3 while interphase FISH demonstrated the spatial overlap expected for adjoining P1s. The interval was previously cloned in cosmids with two small gaps (<20 kb) for which we now have cloned DNA. It is not known at this time if the low-copy P1 origin has conferred stability in these previously uncloned segments. We have surveyed the entire PKD1 interval for expressed sequences using 2 mechanistically distinct approaches, direct cDNA selection and exon trapping. The former method utilizes cloned genomic DNA to enrich for cognate cDNAs from complex cDNA mixtures. The latter approach peruses cloned genomic DNA for the presence of biologically functional splice acceptor/splice donor elements. We compare and contrast these transcriptional mapping approaches and present an expressed sequence map of the PKD1 interval.

  18. Genetic map of the fused locus on mouse Chromosome 17

    SciTech Connect

    Rossi, J.M.; Chen, Hsiuchen; Tilghman, S.M.

    1994-09-01

    Fused (Fu) is a dominant mutation in mice resulting in the asymmetry and fusion of tail vertebrae in heterozygotes. Fu/Fu homozygotes are often viable and can exhibit a duplication of the terminal tail vertebrae resulting in bifurcated tails. There are two more severe alleles at Fu, Kinky (Fu{sup Ki}) and Knobbly (Fu{sup Kb)}, which die between 9 and 10 days of gestation as homozygotes, exhibiting a duplication of the embryonic axis, leading to incomplete or complete twinning. To define the precise map position of the Fu{sup Ki} mutation on mouse Chromosome 17, a 983-animal (Fu{sup Ki} if x Mus spretus) F{sub 1} x + tfl + tf interspecific backcross was generated and scored for Fu{sup Ki}, another tightly linked visible marker tufted (tf), and five linked molecular loci, D17MIT18, D17Leh54, D17Aus57, Hba-ps4, and Pim1. The order and genetic distances between the markers were determined to be centromere-D17MIT18-5.79 cM-D17Leh54-0.85 cM-D17Pri6-0.12 cM-D17Pri7-0.12 eM-Hba-ps4-1.20 cM-D17Pri8-0.48 cM-tf-2.05 cM-Pim1. The Fu{sup Ki} gene could not be genetically separated from three molecular markers, D17Pri6, D17Pri7, and Hba-ps4. Yeasts artificial chromosome clones that contain these tightly linked markers have been isolated to form a contig that contains Fu{sup Ki}. Recombination breakpoints generated through the interspecies backcross were mapped onto the contig and demonstrate that recombination in this region is not random.

  19. Exploiting synteny in Cucumis for mapping of Psm: a unique locus controlling paternal mitochondrial sorting.

    PubMed

    Al-Faifi, Sulieman; Meyer, Jenelle D F; Garcia-Mas, Jordi; Monforte, Antonio J; Havey, Michael J

    2008-08-01

    The three genomes of cucumber show different modes of transmission, nuclear DNA bi-parentally, plastid DNA maternally, and mitochondrial DNA paternally. The mosaic (MSC) phenotype of cucumber is associated with mitochondrial DNA rearrangements and is a valuable tool for studying mitochondrial transmission. A nuclear locus (Psm) has been identified in cucumber that controls sorting of paternally transmitted mitochondrial DNA. Comparative sequencing and mapping of cucumber and melon revealed extensive synteny on the recombinational and sequence levels near Psm and placed this locus on linkage group R of cucumber and G10 of melon. However, the cucumber genomic region near Psm was surprisingly monomorphic with an average of one SNP every 25 kb, requiring that a family from a more diverse cross is produced for fine mapping and eventual cloning of Psm. The cucumber ortholog of Arabidopsis mismatch repair (MSH1) was cloned and it segregated independently of Psm, revealing that this candidate gene is not Psm.

  20. Regional mapping of the phenylalanine hydroxylase gene and the phenylketonuria locus in the human genome

    SciTech Connect

    Lidsky, A.S.; Law, M.L.; Morse, H.G.; Kao, F.T.; Rabin, M.; Ruddle, F.H.; Woo, S.L.C.

    1985-09-01

    Phenylketonuria (PKU) is an autosomal recessive disorder of amino acid metabolism caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase. To define the regional map position of the disease locus and the PAH gene on human chromosome 12, DNA was isolated from human-hamster somatic cell hybrids with various deletions of human chromosome 12 and was analyzed by Southern blot analysis using the human cDNA PAH clone as a hybridization probe. From these results, together with detailed biochemical and cytogenetic characterization of the hybrid cells, the region on chromosome 12 containing the human PAH gene has been defined as 12q14.3..-->..qter. The PAH map position on chromosome 12 was further localized by in situ hybridization of /sup 125/I-labeled human PAH cDNA to chromosomes prepared from a human lymphoblastoid cell line. Results of these experiments demonstrated that the region on chromosome 12 containing the PAH gene and the PKU locus in man is 12q22..-->..12q24.1. These results not only provide a regionalized map position for a major human disease locus but also can serve as a reference point for linkage analysis with other DNA markers on human chromosome 12.

  1. Ehlers-Danlos Syndrome, Hypermobility Type, Is Linked to Chromosome 8p22-8p21.1 in an Extended Belgian Family

    PubMed Central

    Syx, Delfien; Symoens, Sofie; Steyaert, Wouter; De Paepe, Anne; Coucke, Paul J.; Malfait, Fransiska

    2015-01-01

    Joint hypermobility is a common, mostly benign, finding in the general population. In a subset of individuals, however, it causes a range of clinical problems, mainly affecting the musculoskeletal system. Joint hypermobility often appears as a familial trait and is shared by several heritable connective tissue disorders, including the hypermobility subtype of the Ehlers-Danlos syndrome (EDS-HT) or benign joint hypermobility syndrome (BJHS). These hereditary conditions provide unique models for the study of the genetic basis of joint hypermobility. Nevertheless, these studies are largely hampered by the great variability in clinical presentation and the often vague mode of inheritance in many families. Here, we performed a genome-wide linkage scan in a unique three-generation family with an autosomal dominant EDS-HT phenotype and identified a linkage interval on chromosome 8p22-8p21.1, with a maximum two-point LOD score of 4.73. Subsequent whole exome sequencing revealed the presence of a unique missense variant in the LZTS1 gene, located within the candidate region. Subsequent analysis of 230 EDS-HT/BJHS patients resulted in the identification of three additional rare variants. This is the first reported genome-wide linkage analysis in an EDS-HT family, thereby providing an opportunity to identify a new disease gene for this condition. PMID:26504261

  2. Refinement of the Spinal Muscular Atrophy Locus by Genetic and Physical Mapping

    PubMed Central

    Wang, C. H.; Kleyn, P. W.; Vitale, E.; Ross, B. M.; Lien, L.; Xu, J.; Carter, T. A.; Brzustowicz, L. M.; Obici, S.; Selig, S.; Pavone, L.; Parano, E.; Penchaszadeh, G. K.; Munsat, T.; Kunkel, L. M.; Gilliam, T. C.

    1995-01-01

    We report the mapping and characterization of 12 microsatellite markers including 11 novel markers. All markers were generated from overlapping YAC clones that span the spinal muscular atrophy (SMA) locus. PCR amplification of 32 overlapping YAC clones shows that 9 of the new markers (those set in italics) map to the interval between the two previous closest flanking markers (D5S629 and D5S557): cen - D5S6 - D5S125 - D5S435 - D5S1407-D5S629-D5S1410-D5S1411/D5S1412-D5S1413-D5S1414-D5Z8-D5Z9-CATT1-D5Z10/D5Z6-D5S557-D5S1408-D5S1409-D5S637-D5S351-MAP1B-tel. Four of these new markers detect multiple loci in and out of the SMA gene region. Genetic analysis of recombinant SMA families indicates that D5S1413 is a new proximal flanking locus for the SMA gene. Interestingly, among the 40 physically mapped loci, the 14 multilocus markers map contiguously to a genomic region that overlaps, and perhaps helps define, the minimum genetic region encompassing the SMA gene(s). ImagesFigure 2Figure 5 PMID:7825579

  3. Refinement of the spinal muscular atrophy locus by genetic and physical mapping

    SciTech Connect

    Wang, C.H.; Kleyn, P.W.; Vitale, E.; Ross, B.M.; Xu, J.; Carter, T.A.; Brzustowicz, L.M.; Obici, S.; Lien, L.; Selig, S.

    1995-01-01

    We report the mapping and characterization of 12 microsatellite markers including 11 novel markers. All markers were generated from overlapping YAC clones that span the spinal muscular atrophy (SMA) locus. PCR amplification of 32 overlapping YAC clones show that 9 of the new markers (those set in italics) map to the interval between the two previous closest flanking markers (D5S629 and D5S557):cen - D5S6 - D5S125 - D5S435 - D5S1407 - D5S629 - D5S1410 - D5S1411/D5S1412 - D5S1413 - D5S1414 - D5Z8 - D5Z9 - CATT1 - D5Z10/D5Z6 - D5S557 - D5S1408 - D5S1409 - D5S637 - D5S351 - MAP1B - tel. Four of these new markers detect multiple loci in and out of the SMA gene region. Genetic analysis of recombinant SMA families indicates that D5S1413 is a new proximal flanking locus for the SMA gene. Interestingly, among the 40 physically mapped loci, the 14 multilocus markers map contiguously to a genomic region that overlaps, and perhaps helps define, the minimum genetic region encompassing the SMA gene(s). 24 refs., 5 figs., 1 tab.

  4. A novel locus for Meckel-Gruber syndrome, MKS3, maps to chromosome 8q24.

    PubMed

    Morgan, Neil V; Gissen, Paul; Sharif, Saghira Malik; Baumber, Laura; Sutherland, Joan; Kelly, Deirdre A; Aminu, Kingi; Bennett, Christopher P; Woods, C Geoffrey; Mueller, Robert F; Trembath, Richard C; Maher, Eamonn R; Johnson, Colin A

    2002-10-01

    Meckel-Gruber syndrome (MKS), the most common monogenic cause of neural tube defects, is an autosomal recessive disorder characterised by a combination of renal cysts and variably associated features, including developmental anomalies of the central nervous system (typically encephalcoele), hepatic ductal dysplasia and cysts, and polydactyly. Locus heterogeneity has been demonstrated by the mapping of the MKS1locus to 17q21-24 in Finnish kindreds, and of MKS2 to 11q13 in North African-Middle Eastern cohorts. In the present study, we have investigated the genetic basis of MKS in eight consanguineous kindreds, originating from the Indian sub-continent, that do not show linkage to either MKS1 or MKS2. We report the localisation of a third MKS locus ( MKS3) to chromosome 8q24 in this cohort by a genome-wide linkage search using autozygosity mapping. We identified a 26-cM region of autozygosity between D8S586 and D8S1108 with a maximum cumulative two-point LOD score at D8S1179 ( Z(max)=3.04 at theta=0.06). A heterogeneity test provided evidence of one unlinked family. Exclusion of this family from multipoint analysis maximised the cumulative multipoint LOD score at locus D8S1128 ( Z(max)=5.65). Furthermore, a heterozygous SNP in DDEF1, a putative candidate gene, suggested that MKS3 mapped within a 15-cM interval. Comparison of the clinical features of MKS3-linked cases with reports of MKS1- and MKS2-linked kindreds suggests that polydactyly (and possibly encephalocele) appear less common in MKS3-linked families.

  5. Physical mapping of a pollen modifier locus controlling self-incompatibility in apricot and synteny analysis within the Rosaceae.

    PubMed

    Zuriaga, Elena; Molina, Laura; Badenes, María Luisa; Romero, Carlos

    2012-06-01

    S-locus products (S-RNase and F-box proteins) are essential for the gametophytic self-incompatibility (GSI) specific recognition in Prunus. However, accumulated genetic evidence suggests that other S-locus unlinked factors are also required for GSI. For instance, GSI breakdown was associated with a pollen-part mutation unlinked to the S-locus in the apricot (Prunus armeniaca L.) cv. 'Canino'. Fine-mapping of this mutated modifier gene (M-locus) and the synteny analysis of the M-locus within the Rosaceae are here reported. A segregation distortion loci mapping strategy, based on a selectively genotyped population, was used to map the M-locus. In addition, a bacterial artificial chromosome (BAC) contig was constructed for this region using overlapping oligonucleotides probes, and BAC-end sequences (BES) were blasted against Rosaceae genomes to perform micro-synteny analysis. The M-locus was mapped to the distal part of chr.3 flanked by two SSR markers within an interval of 1.8 cM corresponding to ~364 Kb in the peach (Prunus persica L. Batsch) genome. In the integrated genetic-physical map of this region, BES were mapped against the peach scaffold_3 and BACs were anchored to the apricot map. Micro-syntenic blocks were detected in apple (Malus × domestica Borkh.) LG17/9 and strawberry (Fragaria vesca L.) FG6 chromosomes. The M-locus fine-scale mapping provides a solid basis for self-compatibility marker-assisted selection and for positional cloning of the underlying gene, a necessary goal to elucidate the pollen rejection mechanism in Prunus. In a wider context, the syntenic regions identified in peach, apple and strawberry might be useful to interpret GSI evolution in Rosaceae.

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

    PubMed

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

    2015-10-01

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

  7. Homozygosity mapping to the USH2A locus in two isolated populations.

    PubMed

    Fagerheim, T; Raeymaekers, P; Merren, J; Mani, K; Jha, G K; Baumbach, L; Brox, V; Breines, E; Holdø, B E; Holdø, A; Tranebjaerg, L

    1999-02-01

    Usher syndrome is a group of autosomal recessive disorders characterised by progressive visual loss from retinitis pigmentosa and moderate to severe sensorineural hearing loss. Usher syndrome is estimated to account for 6-10% of all congenital sensorineural hearing loss. A gene locus in Usher type II (USH2) families has been assigned to a small region on chromosome 1q41 called the UHS2A locus. We have investigated two families with Usher syndrome from different isolated populations. One family is a Norwegian Saami family and the second family is from the Cayman Islands. They both come from relatively isolated populations and are inbred families suitable for linkage analysis. A lod score of 3.09 and 7.65 at zero recombination was reached respectively in the two families with two point linkage analysis to the USH2A locus on 1q41. Additional homozygosity mapping of the affected subjects concluded with a candidate region of 6.1 Mb. This region spans the previously published candidate region in USH2A. Our study emphasises that the mapped gene for USH2 is also involved in patients from other populations and will have implications for future mutation analysis once the USH2A gene is cloned.

  8. Fine mapping of a major locus controlling plant height using a high-density single-nucleotide polymorphism map in Brassica napus.

    PubMed

    Wang, Yankun; He, Jianbo; Yang, Li; Wang, Yu; Chen, Wenjing; Wan, Shubei; Chu, Pu; Guan, Rongzhan

    2016-08-01

    A saturated map was constructed using SNP markers to fine-map a Brassica napus dominant locus for dwarf mutant onto a 152-kb interval of chromosome A09 containing 14 genes. Major dwarf loci in crops may play important roles in crop improvement and developmental genetics. The present study investigated and fine-mapped a Brassica napus dwarf-dominant locus BnDWF1. Plants carrying the BnDWF1 locus in populations derived from 'zhongshuang11' and Bndwf1 have deep-green leaves and dwarf architecture that differ sharply from tall plants with normal green leaves. BnDWF1, as a major locus controlling plant height, showed a very high heritability (0.91-0.95). To map this locus, a high-density single-nucleotide polymorphism map was constructed, and the BnDWF1 locus was mapped at an interval between single-nucleotide polymorphism markers, M19704 and M19695, on linkage group A09 of B. napus, with five co-segregating single-nucleotide polymorphism markers. Furthermore, fine mapping narrowed the interval harboring BnDWF1 to 152 kb in length in B. napus. This interval contains 14 annotated or predicted genes, seven of which are candidates responsible for the dwarf trait. This study provides an effective foundation for the study of plant height regulation and plant type breeding in B. napus.

  9. Deletion mapping of the DFN3 locus at Xq21.1

    SciTech Connect

    Dahl, N. |; Biancalana, V.; Hanauer, A.

    1994-09-01

    A gene responsible for progressive mixed deafness with stapes fixation and perilymphatic gusher (DFN3) has previously been mapped to Xq132-q21. Molecular characterization of a family with X-linked sensorineural deafness revealed a deletion of locus DXS169 whereas the more telomeric locus DXS26 was intact. Patients affected by DFN3 have previously been reported to be deleted for DXS26 but not for DXS169, and we assumed that a common deletion overlap between the two markers should involve a gene for DFN3. Both loci DXS169 and DXS26 were sequenced and used for PCR-based screening of a mega YAC library (CEPH). One YAC of 1.1 Mb that bridges both loci was isolated. A pulsed-field map was constructed; Alu-PCR clones were generated from the YAC, and their relative positions were determined. Selected Alu clones were sequenced, converted into STSs and used to map the deletion breakpoints. Cosmids, homologous to the YAC, were isolated and mapped to the region corresponding to the deletion overlap. The region should contain at least part of the DFN3 gene and selected cosmids are being used in the search for transcribed sequences.

  10. 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.

  11. Fine Mapping a Locus Controlling Leg Morphology in the Domestic Dog

    PubMed Central

    Quignon, P.; Schoenebeck, J.J.; Chase, K.; Parker, H.G.; Mosher, D.S.; Johnson, G.S.; Lark, K.G.; Ostrander, E.A.

    2012-01-01

    The domestic dog offers a remarkable opportunity to disentangle the genetics of complex phenotypes. Here, we explore a locus, previously identified in the Portuguese water dog (PWD), associated with PC2, a morphological principal component characterized as leg width versus leg length. The locus was initially mapped to a region of 26 Mb on canine chromosome 12 (CFA12) following a genome-wide scan. Subsequent and extensive genotyping of single-nucleotide polymorphisms (SNPs) and haplotype analysis in both the PWD and selected breeds representing phenotypic extremes of PC2 reduced the region from 26 Mb to 500 kb. The proximity of the critical interval to two collagen genes suggests that the phenotype may be controlled by cis-acting mechanisms. PMID:19717540

  12. Genetic analysis of molecular markers for propamocarb residue in Cucumis sativus using quantitative trait locus mapping.

    PubMed

    Xin, M; Wang, L; Ma, B H; Qin, Z W; Zhou, X Y

    2016-11-03

    The use of pesticides to protect plants against harmful organisms, such as pathogenic microorganisms, is one of the most effective ways to improve agricultural production. However, the continuous use of pesticides might present a risk to human health, animals, and the environment. In this study, two cucumber (Cucumis sativus) varieties containing different levels of pesticide residues, D9320 and D0351, were selected to establish an F2 population. A genetic model and genetic linkage map were constructed. The results showed that the heredity of pesticide residues was dominated by an additive effect and was significantly influenced by non-additive factors in cucumber. QCp1 was detected as a quantitative trait locus (QTL) that might be involved in regulating the levels of pesticide residue in cucumber. Moreover, the cucumber genetic map was compared with the LG6 map, and the results indicated that this QTL was closely related to the level of pesticide residue in cucumber.

  13. The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal transduction pathway.

    PubMed Central

    Biggs, W H; Zavitz, K H; Dickson, B; van der Straten, A; Brunner, D; Hafen, E; Zipursky, S L

    1994-01-01

    Mitogen-activated protein (MAP) kinases have been proposed to play a critical role in receptor tyrosine kinase (RTK)-mediated signal transduction pathways. Although genetic and biochemical studies of RTK pathways in Caenorhabditis elegans, Drosophila melanogaster and mammals have revealed remarkable similarities, a genetic requirement for MAP kinases in RTK signaling has not been established. During retinal development in Drosophila, the sevenless (Sev) RTK is required for development of the R7 photoreceptor cell. Components of the signal transduction pathway activated by Sev in the R7 precursor include proteins encoded by the gap1, drk, Sos, ras1 and raf loci. In this report we present evidence that a Drosophila MAP kinase, ERK-A, is encoded by the rolled locus and is required downstream of raf in the Sev signal transduction pathway. Images PMID:8157002

  14. Mapping Point Mutations in the Drosophila Rosy Locus Using Denaturing Gradient Gel Blots

    PubMed Central

    Gray, M.; Charpentier, A.; Walsh, K.; Wu, P.; Bender, W.

    1991-01-01

    Mutations within the rosy locus of Drosophila were mapped using blots of genomic DNA fragments separated on denaturing gradient gels. DNA sequence differences between otherwise identical small rosy DNA fragments were detected among the mutants as mobility shifts on the blots. Mutations were mapped to within a few hundred base pairs of rosy sequence in 100 of 130 mutants tested--a 77% detection rate. The sequence changes in 43 rosy mutations are presented; all but six of these were single base changes. Thirty-four of 36 sequenced mutations induced by the alkylating agents N-ethyl-N-nitrosourea and ethyl methanesulfonate were transitions. All of the mutations mapped in the rosy transcription unit. Twenty-three of the 43 sequenced mutations change the predicted rosy gene polypeptide sequence; the remainder would interrupt protein translation (17), or disrupt mRNA processing (3). PMID:1901817

  15. A new locus for dominant drusen and macular degeneration maps to chromosome 6q14.

    PubMed

    Kniazeva, M; Traboulsi, E I; Yu, Z; Stefko, S T; Gorin, M B; Shugart, Y Y; O'Connell, J R; Blaschak, C J; Cutting, G; Han, M; Zhang, K

    2000-08-01

    To report the localization of a gene causing drusen and macular degeneration in a previously undescribed North American family. Genetic mapping studies were performed using linkage analysis in a single family with drusen and atrophic macular degeneration. The clinical manifestations in this family ranged from fine macular drusen in asymptomatic middle-aged individuals to atrophic macular lesions in two children and two elderly patients. We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644. In a family with autosomal dominant drusen and atrophic macular degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7 (CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of the gene responsible for the disease in this family will provide a better understanding of macular degeneration.

  16. Fine mapping reveals that promotion susceptibility locus 1 (Psl1) is a compound locus with multiple genes that modify susceptibility to skin tumor development.

    PubMed

    Angel, Joe M; Abel, Erika L; Riggs, Penny K; McClellan, S Alex; DiGiovanni, John

    2014-04-03

    Although it is well known that the majority of human cancers occur as the result of exposure to environmental carcinogens, it is clear that not all individuals exposed to a specific environmental carcinogen have the same risk of developing cancer. Considerable evidence indicates that common allelic variants of low-penetrance, tumor susceptibility genes are responsible for this interindividual variation in risk. We previously reported a skin tumor promotion susceptibility locus, Psl1, which maps to the distal portion of chromosome 9, that modified skin tumor promotion susceptibility in the mouse. Furthermore, Psl1 was shown to consist of at least two subloci (i.e., Psl1.1 and Psl1.2) and that glutathione S-transferase alpha 4 (Gsta4), which maps to Psl1.2, is a skin tumor promotion susceptibility gene. Finally, variants of human GSTA4 were found to be associated with risk of nonmelanoma skin cancer. In the current study, a combination of nested and contiguous C57BL/6 congenic mouse strains, each inheriting a different portion of the Psl1 locus from DBA/2, were tested for susceptibility to skin tumor promotion with 12-O-tetradecanoylphorbol-13-acetate. These analyses indicate that Psl1 is a compound locus with at least six genes, including Gsta4, that modify skin tumor promotion susceptibility. More than 550 protein-coding genes map within the Psl1 locus. Fine mapping of the Psl1 locus, along with two-strain haplotype analysis, gene expression analysis, and the identification of genes with amino acid variants, has produced a list of fewer than 25 candidate skin tumor promotion susceptibility genes.

  17. Construction of an integrative regulatory element and variation map of the murine Tst locus.

    PubMed

    Beltram, Jasmina; Morton, Nicholas M; Kunej, Tanja; Horvat, Simon

    2016-06-11

    Given the abundance of new genomic projects and gene annotations, researchers trying to pinpoint causal genetic variants are faced with a challenging task of how to efficiently integrate all current genomic information. The objective of the study was to develop an approach to integrate various genomic annotations for a recently positionally-cloned Tst gene (Thiosulfate Sulfur Transferase, synonym Rhodanese) responsible for the Fob3b2 QTL effect on leanness and improved metabolic parameters. The second aim was to identify and prioritize Tst genetic variants that may be causal for the phenotypic effects. A bioinformatics approach was developed to integrate existing knowledge of regulatory elements of the Tst gene. The entire Tst locus along with flanking segments was sequenced between our unique polygenic mouse Fat and Lean strains that were generated by divergent selection on adiposity for over 60 generations. The bioinformatics-generated regulatory element map of the Tst locus was then combined with genetic variants between the Fat and Lean mice and with comparative analyses of polymorphisms across 17 mouse strains in order to prioritise likely causal polymorphisms. Two candidate regulatory variants were identified, one overlapping an evolutionary constrained Tst intronic element and the other residing in the seed region of a predicted 3'UTR miRNA binding site. This study developed a map of regulatory elements for the Tst locus in mice and identified candidate genetic variants with increased causal likelihood. This map provides a basis for experimental validation and functional analyses of this novel candidate leanness and antidiabetic gene. Our methodological approach is of general utility for analyzing regulation of loci that have limited annotations and experimental evidence and for identifying candidate causal regulatory genetic variants in post-GWAS or post-QTL- cloning studies.

  18. Transcription mapping of the region containing the locus for Treacher Collins syndrome

    SciTech Connect

    Wise, C.A.; Gallardo, T.D.; Li, X.

    1994-09-01

    Treacher Collins syndrome, an autosomal dominant craniofacial disorder and the most common mandibulofacial dysostosis disorder, has been genetically localized to chromosome 5q32. We have previously constructed a YAC contig of approximately 3 megabases cross the region that includes this locus. A single 1.6 Mb YAC from within this contig contains the genetic markers that flank the disease locus as well as two known genes, osteonectin (SPARC) and annexin VI (ANX6). This was converted to cosmid clones by using inter-Alu PCR products from the YAC to screen the LANL chromosome 5-specific cosmid library. One hundred and seventy five cosmids covering the candidate interval were used in a direct selection strategy to enrich for cDNAs encoded by this region. Over 30 selected cDNAs derived from fetal face, fetal brain, activated T cells, placenta, and fetal cranial tissues have been mapped to the region and DNA sequenced. The majority of these cDNAs show little or no homology to previously described DNA sequences. However, one known gene encoding the G (M2) activator protein was selected as a cDNA and mapped to the region immediately flanking the ANX6 locus. A partial cosmid contig covering the critical interval was built from the cosmids by a combination of end walking and fingerprinting methods. Additional polymorphic markers developed from the contig have allowed the Treacher Collins critical region to be further refined to less than 500 kb. Full length cDNA clones that map to this smaller critical region are currently being derived and evaluated in affected pedigrees.

  19. Fine-mapping the POLL locus in Brahman cattle yields the diagnostic marker CSAFG29.

    PubMed

    Mariasegaram, Maxy; Harrison, Blair E; Bolton, Jennifer A; Tier, Bruce; Henshall, John M; Barendse, William; Prayaga, Kishore C

    2012-12-01

    The POLL locus has been mapped to the centromeric region of bovine chromosome 1 (BTA1) in both taurine breeds and taurine-indicine crosses in an interval of approximately 1 Mb. It has not yet been mapped in pure-bred zebu cattle. Despite several efforts, neither causative mutations in candidate genes nor a singular diagnostic DNA marker has been identified. In this study, we genotyped a total of 68 Brahman cattle and 20 Hereford cattle informative for the POLL locus for 33 DNA microsatellites, 16 of which we identified de novo from the bovine genome sequence, mapping the POLL locus to the region of the genes IFNAR2 and SYNJ1. The 303-bp allele of the new microsatellite, CSAFG29, showed strong association with the POLL allele. We then genotyped 855 Brahman cattle for CSAFG29 and confirmed the association between the 303-bp allele and POLL. To determine whether the same association was found in taurine breeds, we genotyped 334 animals of the Angus, Hereford and Limousin breeds and 376 animals of the Brangus, Droughtmaster and Santa Gertrudis composite taurine-zebu breeds. The association between the 303-bp allele and POLL was confirmed in these breeds; however, an additional allele (305 bp) was also associated but not fully predictive of POLL. Across the data, CSAFG29 was in sufficient linkage disequilibrium to the POLL allele in Australian Brahman cattle that it could potentially be used as a diagnostic marker in that breed, but this may not be the case in other breeds. Further, we provide confirmatory evidence that the scur phenotype generally occurs in animals that are heterozygous for the POLL allele.

  20. Juvenile hemochromatosis locus maps to chromosome 1q in a French Canadian population.

    PubMed

    Rivard, Sylvain R; Lanzara, Carmela; Grimard, Doria; Carella, Massimo; Simard, Hervey; Ficarella, Romina; Simard, Raynald; D'Adamo, Adamo Pio; Férec, Claude; Camaschella, Clara; Mura, Cathrine; Roetto, Antonella; De Braekeleer, Marc; Bechner, Lucien; Gasparini, Paolo

    2003-08-01

    Juvenile hemochromatosis (JH) is a rare autosomal recessive disorder that causes iron overload. In the French Canadian region of Saguenay Lac-Saint-Jean the worldwide largest cohort of JH cases has been identified. Here, we report the mapping of this large cohort of cases to the HFE2 locus on chromosome 1q. A maximum multipoint location score of 7.02 was observed with marker D1S2344. A common ancestral haplotype, showing the presence of a founder effect, was identified. The analysis of recombinants allowed us to confirm the JH candidate region.

  1. Fine mapping in tomato using microsynteny with the Arabidopsis genome: the Diageotropica (Dgt) locus

    PubMed Central

    Oh, KwangChul; Hardeman, Kristine; Ivanchenko, Maria G; Ellard-Ivey, Mary; Nebenführ, Andreas; White, TJ; Lomax, Terri L

    2002-01-01

    Background The Arabidopsis thaliana genome sequence provides a catalog of reference genes applicable to comparative microsynteny analysis of other species, facilitating map-based cloning in economically important crops. We have applied such an analysis to the tomato expressed sequence tag (EST) database to expedite high-resolution mapping of the Diageotropica (Dgt) gene within the distal end of chromosome 1 in tomato (Lycopersicon esculentum). Results A BLAST search of the Arabidopsis database with nucleotide sequences of markers that flank the tomato dgt locus revealed regions of microsynteny between the distal end of chromosome 1 in tomato, two regions of Arabidopsis chromosome 4, and one on chromosome 2. Tomato ESTs homeologous to Arabidopsis gene sequences within those regions were converted into co-dominant molecular markers via cleaved amplified polymorphic sequence (CAPS) analysis and scored against an informative backcross mapping population. Six new microsyntenic EST (MEST) markers were rapidly identified in the dgt region, two of which further defined the placement of the Dgt gene and permitted the selection of a candidate tomato bacterial artificial chromosome clone for sequence analysis. Conclusions Microsynteny-based comparative mapping combined with CAPS analysis of recombinant plants rapidly and economically narrowed the dgt mapping region from 0.8 to 0.15 cM. This approach should contribute to developing high-density maps of molecular markers to target-specific regions for positional cloning and marker-assisted selection in a variety of plants. PMID:12225588

  2. Map-Based Cloning of the Gene Associated With the Soybean Maturity Locus E3

    PubMed Central

    Watanabe, Satoshi; Hideshima, Rumiko; Xia, Zhengjun; Tsubokura, Yasutaka; Sato, Shusei; Nakamoto, Yumi; Yamanaka, Naoki; Takahashi, Ryoji; Ishimoto, Masao; Anai, Toyoaki; Tabata, Satoshi; Harada, Kyuya

    2009-01-01

    Photosensitivity plays an essential role in the response of plants to their changing environments throughout their life cycle. In soybean [Glycine max (L.) Merrill], several associations between photosensitivity and maturity loci are known, but only limited information at the molecular level is available. The FT3 locus is one of the quantitative trait loci (QTL) for flowering time that corresponds to the maturity locus E3. To identify the gene responsible for this QTL, a map-based cloning strategy was undertaken. One phytochrome A gene (GmPhyA3) was considered a strong candidate for the FT3 locus. Allelism tests and gene sequence comparisons showed that alleles of Misuzudaizu (FT3/FT3; JP28856) and Harosoy (E3/E3; PI548573) were identical. The GmPhyA3 alleles of Moshidou Gong 503 (ft3/ft3; JP27603) and L62-667 (e3/e3; PI547716) showed weak or complete loss of function, respectively. High red/far-red (R/FR) long-day conditions enhanced the effects of the E3/FT3 alleles in various genetic backgrounds. Moreover, a mutant line harboring the nonfunctional GmPhyA3 flowered earlier than the original Bay (E3/E3; PI553043) under similar conditions. These results suggest that the variation in phytochrome A may contribute to the complex systems of soybean flowering response and geographic adaptation. PMID:19474204

  3. A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.

    PubMed Central

    Kniazeva, M; Chiang, M F; Morgan, B; Anduze, A L; Zack, D J; Han, M; Zhang, K

    1999-01-01

    Stargardt disease (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal-pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait, but many families have been described in which features of the disease are transmitted in an autosomal dominant manner. A recessive locus has been identified on chromosome 1p (STGD1), and dominant loci have been mapped to both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of extended haplotypes localized the disease gene to an approximately 12-cM interval between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new dominant Stargardt-like locus, STGD4. PMID:10205271

  4. Molecular and Recombinational Mapping of Mutations in the Ace Locus of Drosophila melanogaster

    PubMed Central

    Nagoshi, Rodney N.; Gelbart, William M.

    1987-01-01

    The Ace locus in Drosophila melanogaster is known to be the structural gene for acetylcholinesterase. Ace is located in a region of chromosome arm 3R which has been subjected to intensive genetic and molecular analysis. Previous deletion mapping studies have identified a 40-kb region within which the Ace gene resides. This report focuses on the further localization of Ace within this 40-kb interval. Within this region, selective fine structure recombinational analysis was employed to localize three recessive Ace lethals relative to unselected restriction site variations. These three mutations fall into a segment of 7 kb within the Ace interval. Fine structure recombinational analysis was also used to confirm that the Ace- phenotype of one deletion, Df(3R)AceHD1, co-segregated with the molecular deletion. This deletion does not fully remove Ace activity, but it behaves as a recessive Ace lethal. Df(3R)AceHD1 is the most distal Ace lesion identified and indicates that the Ace locus must extend at least 16 kb. Several poly(A)transcripts are detectable in the region defined by the Ace lesions. The position and extent of the Ace locus, as well as the types of transcripts found, is consistent with the recent findings which identified Torpedo-AChE homologous cDNA sequences in this region. PMID:2826288

  5. Molecular and recombinational mapping of mutations in the Ace locus of Drosophila melanogaster

    SciTech Connect

    Nagoshi, R.N.; Gelbart, W.M.

    1987-11-01

    The Ace locus in Drosophila melanogaster is known to be the structural gene for acetylcholinesterase. Ace is located in a region of chromosome arm 3R which has been subjected to intensive genetic and molecular analysis. Previous deletion mapping studies have identified a 40-kb region with which the Ace gene resides. This report focuses on the further localization of Ace within this 40-kb interval. Within this region, selective fine structure recombinational analysis was employed to localize three recessive Ace lethals relative to unselected restriction site variations. These three mutations fall into a segment of 7 kb within the Ace interval. Fine structure recombinational analysis was also used to confirm that the Ace/sup -/ phenotype of one deletion, Df(3R)Ace/sup HD1/, co-segregated with the molecular deletion. This deletion does not fully remove Ace activity, but it behaves as a recessive Ace lethal. Df(3R)Ace/sup HD1/ is the most distal Ace lesion identified and indicates that the Ace locus must extend at least 16 kb. Several poly(A)transcripts are detectable in the region defined by the Ace lesions. The position and extent of the Ace locus, as well as the types of transcripts found, is consistent with the recent findings which identified Torpedo-AChE homologous cDNA sequences in this region.

  6. A new locus for autosomal dominant stargardt-like disease maps to chromosome 4.

    PubMed

    Kniazeva, M; Chiang, M F; Morgan, B; Anduze, A L; Zack, D J; Han, M; Zhang, K

    1999-05-01

    Stargardt disease (STGD) is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal-pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait, but many families have been described in which features of the disease are transmitted in an autosomal dominant manner. A recessive locus has been identified on chromosome 1p (STGD1), and dominant loci have been mapped to both chromosome 13q (STGD2) and chromosome 6q (STGD3). In this study, we describe a kindred with an autosomal dominant Stargardt-like phenotype. A genomewide search demonstrated linkage to a locus on chromosome 4p, with a maximum LOD score of 5.12 at a recombination fraction of.00, for marker D4S403. Analysis of extended haplotypes localized the disease gene to an approximately 12-cM interval between loci D4S1582 and D4S2397. Therefore, this kindred establishes a new dominant Stargardt-like locus, STGD4.

  7. Molecular mapping of the putative gonadoblastoma locus on the Y chromosome.

    PubMed

    Salo, P; Kääriäinen, H; Petrovic, V; Peltomäki, P; Page, D C; de la Chapelle, A

    1995-11-01

    Based on the high incidence of gonadoblastoma in females with XY gonadal dysgenesis or 45,X/46,XY mosaicism, the existence of a susceptibility locus on the Y chromosome (GBY) has been postulated. We attempted to map GBY by making use of a recently developed dense map of Y-chromosomal sequence-tagged sites (STSs). In two female patients with gonadoblastoma, small marker chromosomes contained portions of the Y chromosome, and a single region of overlap could be defined extending from probe pDP97 in interval 4B, which contains the centromere, to marker sY182 in interval 5E of the proximal long arm. This interval is contained in a YAC contig that comprises approximately 4 Mb of DNA. Our findings confirm the previous localization of GBY and greatly refine it. The localization of GBY overlaps with the region to which a putative growth determinant, GCY, was recently assigned.

  8. 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.

  9. Progressive myoclonus epilepsy EPM1 locus maps to a 175-kb interval in distal 21q

    SciTech Connect

    Virtaneva, K.; Miao, J.; Traeskelin, A.L.; Chapelle, A. de la; Lehesjoki, A.E.

    1996-06-01

    The EPM1 locus responsible for progressive myoclonus epilepsy of Unverricht-Lundborg type (MIM 254800) maps to a region in distal chromosome 21q where positional cloning has been hampered by the lack of physical and genetic mapping resolution. We here report the use of a recently constituted contig of cosmid, BAC, and P1 clones that allowed new polymorphic markers to be positioned. These were typed in 53 unrelated disease families from an isolated Finnish population in which a putative single ancestral EPM1 mutation has segregated for an estimated 100 generations. By thus exploiting historical recombinations in haplotype analysis, EPM1 could be assigned to the {approximately}175-kb interval between the markers D21S2040 and D21S1259. 26 refs., 2 figs., 4 tabs.

  10. Familial pseudohyperkalemia maps to the same locus as dehydrated hereditary stomatocytosis (hereditary xerocytosis).

    PubMed

    Iolascon, A; Stewart, G W; Ajetunmobi, J F; Perrotta, S; Delaunay, J; Carella, M; Zelante, L; Gasparini, P

    1999-05-01

    Familial pseudohyperkalemia is a "leaky red blood cell" condition in which the cells show a temperature-dependent loss of potassium (K) from red blood cells when stored at room temperature, manifesting as apparent hyperkalemia. The red blood cells show a reduced lifespan in vivo but there is no frank hemolysis. Studies of cation content and transport show a marginal increase in permeability at 37 degrees C and a degree of cellular dehydration, qualitatively similar to the changes seen in dehydrated hereditary stomatocytosis (hereditary xerocytosis). Physiological studies have shown that the passive leak to K has an abnormal temperature dependence, such that the leak is less sensitive to temperature than that in normal cells. We performed genetic mapping on the original family and found that the condition in this kindred maps to the same locus (16q23-ter) that we have previously identified for an Irish family with dehydrated hereditary stomatocytosis, which does not show the same temperature effects.

  11. High-density linkage mapping revealed suppression of recombination at the sex determination locus in papaya.

    PubMed Central

    Ma, Hao; Moore, Paul H; Liu, Zhiyong; Kim, Minna S; Yu, Qingyi; Fitch, Maureen M M; Sekioka, Terry; Paterson, Andrew H; Ming, Ray

    2004-01-01

    A high-density genetic map of papaya (Carica papaya L.) was constructed using 54 F(2) plants derived from cultivars Kapoho and SunUp with 1501 markers, including 1498 amplified fragment length polymorphism (AFLP) markers, the papaya ringspot virus coat protein marker, morphological sex type, and fruit flesh color. These markers were mapped into 12 linkage groups at a LOD score of 5.0 and recombination frequency of 0.25. The 12 major linkage groups covered a total length of 3294.2 cM, with an average distance of 2.2 cM between adjacent markers. This map revealed severe suppression of recombination around the sex determination locus with a total of 225 markers cosegregating with sex types. The cytosine bases were highly methylated in this region on the basis of the distribution of methylation-sensitive and -insensitive markers. This high-density genetic map is essential for cloning of specific genes of interest such as the sex determination gene and for the integration of genetic and physical maps of papaya. PMID:15020433

  12. Quantitative trait locus analysis of fungal disease resistance factors on a molecular map of grapevine.

    PubMed

    Fischer, B M; Salakhutdinov, I; Akkurt, M; Eibach, R; Edwards, K J; Töpfer, R; Zyprian, E M

    2004-02-01

    A full-sibling F1 population comprising 153 individuals from the cross of 'Regent' x 'Lemberger' was employed to construct a genetic map based on 429 molecular markers. The newly-bred red grapevine variety 'Regent' has multiple field-resistance to fungal diseases inherited as polygenic traits, while 'Lemberger' is a traditional fungus-susceptible cultivar. The progeny segregate quantitatively for resistances to Plasmopara viticola and Uncinula necator, fungal pathogens that threaten viticulture in temperate areas. A double pseudo-testcross strategy was employed to construct the two parental maps under high statistical stringency for linkage to obtain a robust marker frame for subsequent quantitative trait locus (QTL) analysis. In total, 185 amplified fragment length polymorphism, 137 random amplified polymorphic DNA, 85 single sequence repeat and 22 sequence characterized amplified region or cleaved amplified polymorphic sequence markers were mapped. The maps were aligned by co-dominant or doubly heterozygous dominant anchor markers. Twelve pairs of homologous linkage groups could be integrated into consensus linkage groups. Resistance phenotypes and segregating characteristics were scored as quantitative traits in three or four growing seasons. Interval mapping reproducibly localized genetic factors that correlated with fungal disease resistances to specific regions on three linkage groups of the maternal 'Regent' map. A QTL for resistance to Uncinula necator was identified on linkage group 16, and QTLs for endurance to Plasmopara viticola on linkage groups 9 and 10 of 'Regent'. Additional QTLs for the onset of berry ripening ("veraison"), berry size and axillary shoot growth were identified. Berry color segregated as a simple trait in this cross of two red varieties and was mapped as a morphological marker. Six markers derived from functional genes could be localized. This dissection of polygenic fungus disease resistance in grapevine allows the development of

  13. Identification of quantitative trait locus (QTL) linked to dorsal fin length from preliminary linkage map of molly fish, Poecilia sp.

    PubMed

    Keong, Bun Poh; Siraj, Siti Shapor; Daud, Siti Khalijah; Panandam, Jothi Malar; Rahman, Arina Nadia Abdul

    2014-02-15

    A preliminary linkage map was constructed by applying backcross and testcross strategy using microsatellite (SSR) markers developed for Xiphophorus and Poecilia reticulata in ornamental fish, molly Poecilia sp. The linkage map having 18 SSR loci consisted of four linkage groups that spanned a map size of 516.1cM. Association between genotypes and phenotypes was tested in a random fashion and QTL for dorsal fin length was found to be linked to locus Msb069 on linkage group 2. Coincidentally, locus Msb069 was also reported as putative homologue primer pairs containing SSRs repeat motif which encoded hSMP-1, a sex determining locus. Dorsal fin length particularly in males of Poecilia latipinna is an important feature during courtship display. Therefore, we speculate that both dorsal fin length and putative hSMP-1 gene formed a close proximity to male sexual characteristics.

  14. Refined mapping of a hypertension susceptibility locus on rat chromosome 12.

    PubMed

    Prisco, Sasha Z; Prokop, Jeremy W; Sarkis, Allison B; Yeo, Nan Cher; Hoffman, Matthew J; Hansen, Colin C; Jacob, Howard J; Flister, Michael J; Lazar, Jozef

    2014-10-01

    Previously, we found that transferring 6.1 Mb of salt-sensitive (SS) chromosome 12 (13.4-19.5 Mb) onto the consomic SS-12(BN) background significantly elevated mean arterial pressure in response to an 8% NaCl diet (178±7 versus 144±2 mm Hg; P<0.001). Using congenic mapping, we have now narrowed the blood pressure locus by 86% from a 6.1-Mb region containing 133 genes to an 830-kb region (chr12:14.36-15.19 Mb) with 14 genes. Compared with the SS-12(BN) consomic, the 830-kb blood pressure locus was associated with a ∆+15 mm Hg (P<0.01) increase in blood pressure, which coincided with elevated albuminuria (∆+32 mg/d; P<0.001), proteinuria (∆+48 mg/d; P<0.01), protein casting (∆+154%; P<0.05), and renal fibrosis (∆+79%; P<0.05). Of the 14 genes residing in the 830-kb locus, 8 were differentially expressed, and among these, Chst12 (carbohydrate chondroitin 4 sulfotransferase 12) was most consistently downregulated by 2.6- to 4.5-fold (P<0.05) in both the renal medulla and cortex under normotensive and hypertensive conditions. Moreover, whole genome sequence analysis of overlapping blood pressure loci revealed an ≈86-kb region (chr12:14 541 567-14 627 442 bp) containing single-nucleotide variants near Chst12 that are unique to the hypertensive SS strain when compared with the normotensive Brown Norway, Dahl salt-resistant, and Wistar-Kyoto strains. Finally, the 830-kb interval is syntenic to a region on human chromosome 7 that has been genetically linked to blood pressure, suggesting that insight gained from our SS-12(BN) congenic strain may be translated to a better understanding of human hypertension. © 2014 American Heart Association, Inc.

  15. Homozygosity Mapping Identifies an Additional Locus for Wolfram Syndrome on Chromosome 4q

    PubMed Central

    El-Shanti, Hatem; Lidral, Andrew C.; Jarrah, Nadim; Druhan, Lawrence; Ajlouni, Kamel

    2000-01-01

    Wolfram syndrome, which is sometimes referred to as “DIDMOAD” (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an autosomal recessive neurodegenerative disorder for which only insulin-dependent diabetes mellitus and optic atrophy are necessary to make the diagnosis. Researchers have mapped Wolfram syndrome to chromosome 4p16.1, and, recently, a gene encoding a putative transmembrane protein has been cloned and mutations have been identified in patients. To pursue the possibility of locus heterogeneity, 16 patients from four different families were recruited. These patients, who have the Wolfram syndrome phenotype, also have additional features that have not previously been reported. There is an absence of diabetes insipidus in all affected family members. In addition, several patients have profound upper gastrointestinal ulceration and bleeding. With the use of three microsatellite markers (D4S432, D4S3023, and D4S2366) reported to be linked to the chromosome 4p16.1 locus, we significantly excluded linkage in three of the four families. The two affected individuals in one family showed homozygosity for all three markers from the region of linkage on chromosome 4p16.1. For the other three families, genetic heterogeneity for Wolfram syndrome was verified by demonstration of linkage to chromosome 4q22-24. In conclusion, we report the unique clinical findings and linkage-analysis results of 16 patients with Wolfram syndrome and provide further evidence for the genetic heterogeneity of this disorder. We also provide data on a new locus that plays a role in the etiology of insulin-dependent diabetes mellitus. PMID:10739754

  16. Fine genetic mapping of the Co locus controlling columnar growth habit in apple.

    PubMed

    Bai, Tuanhui; Zhu, Yuandi; Fernández-Fernández, Felicidad; Keulemans, Johan; Brown, Susan; Xu, Kenong

    2012-05-01

    Tree architecture is an important, complex and dynamic trait affected by diverse genetic, ontogenetic and environmental factors. 'Wijcik McIntosh', a columnar (reduced branching) sport of 'McIntosh' and a valuable genetic resource, has been used intensively in apple-breeding programs for genetic improvement of tree architecture. The columnar growth habit is primarily controlled by the dominant allele of gene Co (columnar) on linkage group-10. But the Co locus is not well mapped and the Co gene remains unknown. To precisely map the Co locus and to identify candidate genes of Co, a sequence-based approach using both peach and apple genomes was used to develop new markers linked more tightly to Co. Five new simple sequence repeats markers were developed (C1753-3520, C18470-25831, C6536-31519, C7223-38004 and C7629-22009). The first four markers were obtained from apple genomic sequences on chromosome-10, whereas the last (C7629-22009) was from an unanchored apple contig that contains an apple expressed sequence tag CV082943, which was identified through synteny analysis between the peach and apple genomes. Genetic mapping of these five markers in four F(1) populations of 528 genotypes and 290 diverse columnar selections/cultivars (818 genotypes in total) delimited the Co locus in a genetic interval with 0.37 % recombination between markers C1753-3520 and C7629-22009. Marker C18470-25831 co-segregates with Co in the 818 genotypes studied. The Co region is estimated to be 193 kb and contains 26 predicted gene in the 'Golden Delicious' genome. Among the 26 genes, three are putative LATERAL ORGAN BOUNDARIES (LOB) DOMAIN (LBD) containing transcription factor genes known of essential roles in plant lateral organ development, and are therefore considered as strong candidates of Co, designated MdLBD1, MdLBD2, and MdLBD3. Although more comprehensive studies are required to confirm the function of MdLBD1-3, the present work represents an important step forward to better

  17. Refinement of the spinal muscular atrophy locus to the interval between D5S435 and MAP1B

    SciTech Connect

    Soares, V.M.; Brzustowicz, L.M.; Kleyn, P.W.; Knowles, J.A.; Palmer, D.A.; Asokan, S.; Penchaszadeh, G.K.; Gilliam, T.C. ); Munsat, T.L. )

    1993-02-01

    The childhood-onset SMA locus has been mapped to chromosome 5q13, in a region bounded by the proximal locus, D5S6, and the closely linked distal loci, D5S112 and MAP1B. We now describe a highly polymorphic, tightly linked microsatellite marker (D5S435) that is very likely the closet proximal marker to the SMA locus. Multipoint linkage analysis firmly establishes the following order of markers at 5q13; centromere-D5S76-D5S6-D5S435-MAP1B/D5S112-D5S39-telomere. The data indicate that SMA resides in an approximately 0.7-cM (range 01.-2.1) region between D5S435 and MAP1B. This finding reduces by approximately fourfold the genetic region that most likely harbors the SMA locus and will facilitate the physical mapping and cloning of the disease gene region. 24 refs., 3 figs., 1 tab.

  18. Fine-structure genetic map of the cysB locus in Salmonella typhimurium.

    PubMed Central

    Cheney, R W; Kredich, N M

    1975-01-01

    A genetic map of the cysB region of the Salmonella typhimurium chromosome was constructed using bacteriophage P22-mediated transduction. Strains bearing delta (supX cysB) mutations were employed to divide this regulatory locus into 12 segments containing a total of 39 single-site mutations. Twenty-five of these single-site mutations were further ordered by reciprocal three-point crosses. The results do not support the concept of multiple cistrons at cysB and suggest that the abortive transductants previously observed in crosses between certain cysB mutants were due to intracistronic complementation. The prototrophic cys-1352 mutation, which causes the constitutive expression of the cysteine biosynthetic enzymes, was found to lie within the cysB region itself. It is bracketed by mutations, which lead to an inability to derepress for these enzymes and result in auxotrophy for cysteine. PMID:1104581

  19. Mapping of a complicated familial spastic paraplegia to locus SPG4 on chromosome 2p.

    PubMed Central

    Heinzlef, O; Paternotte, C; Mahieux, F; Prud'homme, J F; Dien, J; Madigand, M; Pouget, J; Weissenbach, J; Roullet, E; Hazan, J

    1998-01-01

    Autosomal dominant familial spastic paraplegia (AD-FSP) is a degenerative disorder of the central motor system characterised by progressive spasticity of the lower limbs. AD-FSP has been divided into pure and complicated forms. Pure AD-FSP is genetically heterogeneous; three loci have been mapped to chromosomes 14q (SPG3), 2p (SPG4), and 15q (SPG6), whereas no loci responsible for complicated forms have been identified to date. Here we report linkage to the SPG4 locus in a three generation family with AD-FSP complicated by dementia and epilepsy. Assuming that both forms of AD-FSP are caused by mutations involving the same FSP gene, analysis of recombination events in this family positions the SPG4 gene within a 0 cM interval flanked by loci D2S2255 and D2S2347. PMID:9507385

  20. Mapping of a quantitative trait locus for blood pressure on rat chromosome 2.

    PubMed Central

    Deng, A Y; Dene, H; Rapp, J P

    1994-01-01

    A genetic map for rat chromosome 2 that includes five candidate genes for blood pressure regulation was constructed in a region containing a quantitative trait locus (QTL) for blood pressure. Two F2 populations of male rats raised on high salt (8% NaCI) diet from weaning were studied: F2(WKY x S), derived from a cross of Dahl salt-sensitive rats (S) and Wistar-Kyoto rats (WKY); and F2(MNS x S), derived from a cross of S rats and Milan normotensive strain (MNS). In both populations a blood pressure QTL was localized between Na+,K(+)-ATPase alpha 1 isoform and calmodulin-dependent protein kinase II-delta loci. The LOD score for existence of this blood pressure QTL based on the combined populations (n = 330) was 5.66 and accounted for 9.2% of the total variance and 26% of the genetic variance. PMID:8040284

  1. A locus for bilateral occipital polymicrogyria maps to chromosome 6q16-q22.

    PubMed

    Ben Cheikh, Bouchra Ouled Amar; Baulac, Stéphanie; Lahjouji, Fatiha; Bouhouche, Ahmed; Couarch, Philippe; Khalili, Naima; Regragui, Wafae; Lehericy, Stéphane; Ruberg, Merle; Benomar, Ali; Heath, Simon; Chkili, Taib; Yahyaoui, Mohamed; Jiddane, Mohamed; Ouazzani, Reda; LeGuern, Eric

    2009-02-01

    We describe the clinical, radiographic, and genetic features of a large consanguineous Moroccan family in which bilateral occipital polymicrogyria segregated as an autosomal recessive trait. Six affected members of the family had partial complex seizures often associated with behavioral abnormalities. On MRI, three patients had a thickened irregular cortex in the lateral occipital lobes with small gyri. A high-density genome-wide scan with 10,000 SNPs established linkage by homozygosity mapping to a 14-Mb region on chromosome 6q16-q22. Candidate genes by function (TUBE1, GRIK2, GPRC6A, GPR6, NR2E1, MICAL1, and MARCKS) in this locus were screened for mutations.

  2. The locus for a novel syndromic form of neuronal intestinal pseudoobstruction maps to Xq28.

    PubMed Central

    Auricchio, A.; Brancolini, V.; Casari, G.; Milla, P. J.; Smith, V. V.; Devoto, M.; Ballabio, A.

    1996-01-01

    The neuronal type of primary chronic idiopathic intestinal pseudoobstruction (CIIP) results from the developmental failure of enteric neurons to migrate or differentiate correctly. This leads to intestinal motility disorders, which are characterized by symptoms and signs of bowel obstruction in the absence of a mechanical obstacle. Most of these conditions are congenital, and among them some are inherited. One syndromic condition characterized by intestinal pseudoobstruction with morphological abnormalities of the argyrophil neurons in the myenteric plexus, associated with short small bowel, malrotation, and pyloric hypertrophy, has been previously described. We have studied a family affected by this disorder, in which the disease appeared to segregate as an X-linked recessive trait. In order to map the CIIP locus in this family, we performed linkage analysis in 26 family members by use of highly polymorphic microsatellite markers from the X chromosome. One of these markers, DXYS154, located in the distal part of Xq28, shows no recombination with a maximum lod score of 2.32. Multipoint analysis excluded linkage with markers spanning other regions of the X chromosome. Our results, integrated with the current genetic and physical map of Xq28, determine the order of loci as cen-DXS15-(CIIPX)-DXS1108/DXYS154-tel. This study establishes, for the first time, the mapping assignment of a neuropathic form of CIIP other than Hirschsprung disease. Images Figure 1 PMID:8644737

  3. 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.

  4. Fine mapping of the 9q31 Hirschsprung’s disease locus

    PubMed Central

    Tang, C. S.; Sribudiani, Y.; Miao, X. P.; de Vries, A. R.; Burzynski, G.; So, M. T.; Leon, Y. Y.; Yip, B. H.; Osinga, J.; Hui, K. J. W. S.; Verheij, J. B. G. M.; Cherny, S. S.; Tam, P. K. H.; Sham, P. C.

    2010-01-01

    Hirschsprung’s disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 × 10−6 [OR = 3.32 (1.99, 5.59)] after replication. The HSCR-association found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system. Electronic supplementary material The online version of this article (doi:10.1007/s00439-010-0813-8) contains supplementary material, which is available to authorized users. PMID:20361209

  5. Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus.

    PubMed

    Horne, Hisani N; Chung, Charles C; Zhang, Han; Yu, Kai; Prokunina-Olsson, Ludmila; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Iwata, Hiroji; Dörk, Thilo; Bogdanova, Natalia V; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chenevix-Trench, Georgia; Wu, Anna H; Ven den Berg, David; Smeets, Ann; Zhao, Hui; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Barile, Monica; Couch, Fergus J; Vachon, Celine; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Marchand, Loic Le; Goldberg, Mark S; Teo, Soo H; Taib, Nur A M; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Shrubsole, Martha; Winqvist, Robert; Jukkola-Vuorinen, Arja; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; Martens, John W M; Li, Jingmei; Lu, Wei; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Shah, Mitul; Luccarini, Craig; Baynes, Caroline; Harrington, Patricia; Kang, Daehee; Choi, Ji-Yeob; Hartman, Mikael; Chia, Kee Seng; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; Brennan, Paul; Slager, Susan; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hou, Ming-Feng; Swerdlow, Anthony; Orr, Nick; Simard, Jacques; Hall, Per; Pharoah, Paul D P; Easton, Douglas F; Chanock, Stephen J; Dunning, Alison M; Figueroa, Jonine D

    2016-01-01

    The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.

  6. Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

    PubMed Central

    Horne, Hisani N.; Chung, Charles C.; Zhang, Han; Yu, Kai; Prokunina-Olsson, Ludmila; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Hopper, John L.; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A.; Beckmann, Matthias W.; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Anton-Culver, Hoda; Neuhausen, Susan L.; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Iwata, Hiroji; Dörk, Thilo; Bogdanova, Natalia V.; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chenevix-Trench, Georgia; Wu, Anna H.; ven den Berg, David; Smeets, Ann; Zhao, Hui; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Barile, Monica; Couch, Fergus J.; Vachon, Celine; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Marchand, Loic Le; Goldberg, Mark S.; Teo, Soo H.; Taib, Nur A. M.; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Shrubsole, Martha; Winqvist, Robert; Jukkola-Vuorinen, Arja; Andrulis, Irene L.; Knight, Julia A.; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; Martens, John W. M.; Li, Jingmei; Lu, Wei; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S.; Blot, William; Cai, Qiuyin; Shah, Mitul; Luccarini, Craig; Baynes, Caroline; Harrington, Patricia; Kang, Daehee; Choi, Ji-Yeob; Hartman, Mikael; Chia, Kee Seng; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; Brennan, Paul; Slager, Susan; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hou, Ming-Feng; Swerdlow, Anthony; Orr, Nick; Simard, Jacques; Hall, Per; Pharoah, Paul D. P.

    2016-01-01

    The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799–121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000–120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08–1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive. PMID:27556229

  7. Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4

    PubMed Central

    Manku, Harinder; Langefeld, Carl D.; Guerra, Sandra G.; Malik, Talat H.; Alarcon-Riquelme, Marta; Anaya, Juan-Manuel; Bae, Sang-Cheol; Boackle, Susan A.; Brown, Elizabeth E.; Criswell, Lindsey A.; Freedman, Barry I.; Gaffney, Patrick M.; Gregersen, Peter A.; Guthridge, Joel M.; Han, Sang-Hoon; Harley, John B.; Jacob, Chaim O.; James, Judith A.; Kamen, Diane L.; Kaufman, Kenneth M.; Kelly, Jennifer A.; Martin, Javier; Merrill, Joan T.; Moser, Kathy L.; Niewold, Timothy B.; Park, So-Yeon; Pons-Estel, Bernardo A.; Sawalha, Amr H.; Scofield, R. Hal; Shen, Nan; Stevens, Anne M.; Sun, Celi; Gilkeson, Gary S.; Edberg, Jeff C.; Kimberly, Robert P.; Nath, Swapan K.; Tsao, Betty P.; Vyse, Tim J.

    2013-01-01

    We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P = 1.71×10−34, OR = 1.43[1.26–1.60]) and rs1234317-T (P = 1.16×10−28, OR = 1.38[1.24–1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5′ region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5′ risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and

  8. The Locus Lookup Tool at MaizeGDB: Identification of Genomic Regions in Maize by Integrating Sequence Information with Physical and Genetic Maps

    USDA-ARS?s Scientific Manuscript database

    Methods to automatically integrate sequence information with physical and genetic maps are scarce. The Locus Lookup Tool enables researchers to define windows of genomic sequence likely to contain loci of interest where only genetic or physical mapping associations are reported. Using the Locus Look...

  9. Quantitative trait locus mapping for seed mineral concentrations in two Arabidopsis thaliana recombinant inbred populations.

    PubMed

    Waters, Brian M; Grusak, Michael A

    2008-01-01

    Biofortification of foods, achieved by increasing the concentrations of minerals such as iron (Fe) and zinc (Zn), is a goal of plant scientists. Understanding genes that influence seed mineral concentration in a model plant such as Arabidopsis could help in the development of nutritionally enhanced crop cultivars. Quantitative trait locus (QTL) mapping for seed concentrations of calcium (Ca), copper (Cu), Fe, potassium (K), magnesium (Mg), manganese (Mn), phosphorus (P), sulfur (S), and Zn was performed using two recombinant inbred line (RIL) populations, Columbia (Col) x Landsberg erecta (Ler) and Cape Verde Islands (Cvi) x Ler, grown on multiple occasions. QTL mapping was also performed using data from silique hulls and the ratio of seed:hull mineral concentration of the Cvi x Ler population. Over 100 QTLs that affected seed mineral concentration were identified. Twenty-nine seed QTLs were found in more than one experiment, and several QTLs were found for both seed and hull mineral traits. A number of candidate genes affecting seed mineral concentration are discussed. These results indicate that A. thaliana is a suitable and convenient model for discovery of genes that affect seed mineral concentration. Some strong QTLs had no obvious candidate genes, offering the possibility of identifying unknown genes that affect mineral uptake and translocation to seeds.

  10. A novel locus for non-syndromic sensorineural deafness (DFN6) maps to chromosome Xp22.

    PubMed

    del Castillo, I; Villamar, M; Sarduy, M; Romero, L; Herraiz, C; Hernández, F J; Rodríguez, M; Borrás, I; Montero, A; Bellón, J; Tapia, M C; Moreno, F

    1996-09-01

    Non-syndromic X-linked deafness is highly heterogeneous. At least five different clinical forms have been described, but only two loci have been mapped. Here we report a Spanish family affected by a previously undescribed X-linked form of hearing impairment. Deafness is non-syndromic, sensorineural, and progressive. In affected males, the auditory impairment is first detected at school age, affecting mainly the high frequencies. Later it evolves to become severe to profound, involving all frequencies for adulthood. Carrier females manifest a moderate hearing impairment in the high frequencies, with the onset delayed to the fourth decade of life. Deafness was assumed to be X-linked dominant, with incomplete penetrance and variable expressivity in carrier females. The family was genotyped for a set of microsatellite markers evenly spaced at intervals of about 10 cM. We found evidence of linkage to markers in the Xp22 region (maximum lod score of 5.30 at theta = 0.000 for DXS8036 and for DXS8022). The position of the novel deafness locus (DFN6) was refined by haplotype analysis. Mapping of the breakpoints in two critical recombinants allowed us to define an interval for DFN6, delimited by DXS7108 on the distal side and by DXS7105 on the proximal side, and spanning a genetic distance of about 15 cM.

  11. Fine mapping of locus Xq25.1-27-2 for a low caries experience phenotype

    PubMed Central

    Küchler, Erika C.; Feng, Ping; Deeley, Kathleen; Fitzgerald, Carly A.; Meyer, Chelsea; Gorbunov, Anastasia; Bezamat, Mariana; Reis, Maria Fernanda; Noel, Jacqueline; Kouzbari, M. Zahir; Granjeiro, José M.; Antunes, Leonardo S.; Antunes, Livia A.; de Abreu, Fernanda Volpe; Costa, Marcelo C.; Tannure, Patricia N.; Seymen, Figen; Koruyucu, Mine; Patir, Asli; Vieira, Alexandre R.

    2014-01-01

    Objective The purpose of this study was to fine map the locus Xq25.1-27-2 in order to identify genetic contributors involved in low caries experience. Design Seventy-two families from the Philippines were studied. Caries experience was recorded and genomic DNA extracted from peripheral blood was obtained from all subjects. One hundred and twenty-eight polymorphisms in the locus Xq25.1-27-2, a region that contains 24 genes, were genotyped. Association between caries experience and alleles was tested using the transmission disequilibrium test (TDT). This initial analysis was followed by experiments with DNA samples from 1,481 subjects from Pittsburgh, 918 children from Brazil, and 275 children from Turkey in order to follow up the results found in the Filipino families. Chi-square or Fisher’s exact tests were used. Sequencing of the coding regions and exon-intron boundaries of MST4 and FGF13 were also performed on 91 women from Pittsburgh. Results Statistically significant association with low caries experience was found for 11 markers in Xq25.1-27-2 in the Filipino families. One marker was in MST4, another marker was in FGF13, and the remaining markers were in intergenic regions. Haplotype analysis also confirmed these results, but the follow up studies with DNA samples from Pittsburgh, Brazil, and Turkey showed associations for a subset of the 11 markers. No coding mutations were identified by sequencing. Conclusions Our study failed to conclusively demonstrate that genetic factors in Xq25.1-27-2 contribute to caries experience in multiple populations. PMID:24632093

  12. High-resolution mapping of the X-linked hypohidrotic ectodermal dysplasia (EDA) locus

    PubMed Central

    Zonana, J.; Jones, M.; Browne, D.; Litt, M.; Kramer, P.; Becker, H. W.; Brockdorff, N.; Rastan, S.; Davies, K. P.; Clarke, A.; Thomas, N. S. T.

    1992-01-01

    The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. We have extended our previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009–.075. Multipoint analyses gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci could be inferred from a human/rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosities of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that cosegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXS732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively. PMID:1357963

  13. High-resolution mapping of the x-linked hypohidrotic ectodermal dysplasia (EDA) locus

    SciTech Connect

    Zonana, J.; Jones, M.; Litt, M.; Kramer, P.; Browne, D.; Becker, H.W. ); Brockdorff, N.; Rastan, S. ); Davies, K.P.; Clarke, A. )

    1992-11-01

    The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. The authors have extended previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analysis gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci could be inferred from a human-rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosites of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that consegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXSA732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively. 36 refs., 1 fig., 5 tabs.

  14. FISH-mapping of the 5S rDNA locus in chili peppers (Capsicum-Solanaceae).

    PubMed

    Aguilera, Patricia M; Debat, Humberto J; Scaldaferro, Marisel A; Martí, Dardo A; Grabiele, Mauro

    2016-03-01

    We present here the physical mapping of the 5S rDNA locus in six wild and five cultivated taxa of Capsicum by means of a genus-specific FISH probe. In all taxa, a single 5S locus per haploid genome that persistently mapped onto the short arm of a unique metacentric chromosome pair at intercalar position, was found. 5S FISH signals of almost the same size and brightness intensity were observed in all the analyzed taxa. This is the first cytological characterization of the 5S in wild taxa of Capsicum by using a genus-derived probe, and the most exhaustive and comprehensive in the chili peppers up to now. The information provided here will aid the cytomolecular characterization of pepper germplasm to evaluate variability and can be instrumental to integrate physical, genetic and genomic maps already generated in the genus.

  15. High-density genetic map construction and gene mapping of pericarp color in wax gourd using specific-locus amplified fragment (SLAF) sequencing.

    PubMed

    Jiang, Biao; Liu, Wenrui; Xie, Dasen; Peng, Qingwu; He, Xiaoming; Lin, Yu'e; Liang, Zhaojun

    2015-12-09

    High-density map is a valuable tool for genetic and genomic analysis. Although wax gourd is a widely distributed vegetable of Cucurbitaceae and has important medicinal and health value, no genetic map has been constructed because of the lack of efficient markers. Specific-locus amplified fragment sequencing (SLAF-seq) is a newly developed high-throughput strategy for large-scale single nucleotide polymorphism (SNP) discovery and genotyping. In our present study, we constructed a high-density genetic map by using SLAF-seq and identified a locus controlling pericarp color in wax gourd. An F2 population of 140 individuals and their two parents were subjected to SLAF-seq. A total of 143.38 M pair-end reads were generated. The average sequencing depth was 26.51 in the maternal line (B214), 27.01 in the parental line (B227), and 5.11 in each F2 individual. When filtering low-depth SLAF tags, a total of 142,653 high-quality SLAFs were detected, and 22,151 of them were polymorphic, with a polymorphism rate of 15.42 %. And finally, 4,607 of the polymorphic markers were selected for genetic map construction, and 12 linkage groups (LGs) were generated. The map spanned 2,172.86 cM with an average distance between adjacent markers for 0.49 cM. The inheritance of pericarp color was also studied, which showed that the pericarp color was controlled by one single gene. And based on the newly constructed high-density map, a single locus locating on chromosome 5 was identified for controlling the pericarp color of wax gourd. This is the first report of high-density genetic map construction and gene mapping in wax gourd, which will be served as an invaluable tool for gene mapping, marker assisted breeding, map-based gene cloning, comparative mapping and draft genome assembling of wax gourd.

  16. 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.

  17. Two pedigrees segregating Duane’s retraction syndrome as a dominant trait map to the DURS2 genetic locus

    PubMed Central

    Engle, Elizabeth C.; Andrews, Caroline; Law, Krystal; Demer, Joseph L.

    2010-01-01

    PURPOSE To determine the molecular etiologies of Duane’s retraction syndrome (DRS), we are investigating its genetic bases. We have previously identified the transcription factors SALL4 and HOXA1 as the genes mutated in DRS with radial anomalies, and in DRS with deafness, vascular anomalies, and cognitive deficits, respectively. We know less, however, about the genetic etiology of DRS when it occurs in isolation, and only one genetic locus for isolated DRS, the DURS2 locus on chromosome 2, has been mapped to date. Toward the goal of identifying the DURS2 gene, we have ascertained and studied two pedigrees that segregate DRS as a dominant trait. METHODS We enrolled members of two large dominant DRS pedigrees into our ongoing study of the genetic basis of the congenital cranial dysinnervation disorders, and conducted linkage analysis to determine if their DRS phenotype maps to the DURS2 locus. RESULTS By haplotype analysis, the DRS phenotype in each family co-segregates with markers spanning the DURS2 region, and linkage analysis reveals maximum lod scores of >2, establishing that the DRS phenotype in these two pedigrees maps to the DURS2 locus. CONCLUSIONS These two pedigrees double the published pedigrees known to map to the DURS2 locus, and can thus contribute toward the search for the DURS2 gene. The affected members represent a genetically defined population of DURS2-linked DRS individuals, and hence studies of their clinical and structural features can enhance our understanding of the DURS2 phenotype, as described in the companion paper. PMID:17197532

  18. 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

  19. A novel locus for disseminated superficial actinic porokeratosis maps to chromosome 16q24.1-24.3.

    PubMed

    Luan, Jing; Niu, Zhenmin; Zhang, Jing; Crosby, Meredith E; Zhang, Zhenghua; Chu, Xun; Wang, Zhimin; Huang, Wei; Xiang, Leihong; Zheng, Zhizhong

    2011-03-01

    Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant keratinization disorder with genetic heterogeneity characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Thus far, there have been three susceptible loci determined for DSAP and one locus for disseminated superficial porokeratosis (DSP), i.e. 12q23.2-24.1, 15q25.1-26.1, 1p31.3-p31.1 and 18p11.3. Moreover, the locus for porokeratosis palmaris plantaris et disseminata (PPPD) was mapped to 12q24.1-24.2, which overlapped with the first DSAP locus. Following the exclusion of these known loci in a four-generation Chinese DSAP family, we performed a genome-wide linkage analysis and identified a new locus on chromosome 16q24.1-24.3. The maximum two-point LOD score of 3.73 was obtained with the marker D16S3074 at a recombination fraction θ of 0.00. Haplotype analysis defined the critical 17.4-cM region for DSAP between D16S3091 and D16S413. This is regarded to be the forth locus for DSAP (DSAP4). ATP2C1 was sequenced as a candidate gene, however, no mutation was found. Further investigation for the genetic basis of DSAP is under way. © Springer-Verlag 2010

  20. Linkage mapping of the primary disease locus for collie eye anomaly.

    PubMed

    Lowe, Jennifer K; Kukekova, Anna V; Kirkness, Ewen F; Langlois, Mariela C; Aguirre, Gustavo D; Acland, Gregory M; Ostrander, Elaine A

    2003-07-01

    Collie eye anomaly (cea) is a hereditary ocular disorder affecting development of the choroid and sclera segregating in several breeds of dog, including rough, smooth, and Border collies and Australian shepherds. The disease is reminiscent of the choroidal hypoplasia phenotype observed in humans in conjunction with craniofacial or renal abnormalities. In dogs, however, the clinical phenotype can vary significantly; many dogs exhibit no obvious clinical consequences and retain apparently normal vision throughout life, while severely affected animals develop secondary retinal detachment, intraocular hemorrhage, and blindness. We report genetic studies establishing that the primary cea phenotype, choroidal hypoplasia, segregates as an autosomal recessive trait with nearly 100% penetrance. We further report linkage mapping of the primary cea locus to a 3.9-cM region of canine chromosome 37 (LOD = 22.17 at theta = 0.076), in a region corresponding to human chromosome 2q35. These results suggest the presence of a developmental regulatory gene important in ocular embryogenesis, with potential implications for other disorders of ocular vascularization.

  1. A New Locus for Generalized Epilepsy with Febrile Seizures Plus Maps to Chromosome 2

    PubMed Central

    Lopes-Cendes, I.; Scheffer, I. E.; Berkovic, S. F.; Rousseau, M.; Andermann, E.; Rouleau, G. A.

    2000-01-01

    Summary Generalized epilepsy with febrile seizures plus (GEFS+) is a recently recognized but relatively common form of inherited childhood-onset epilepsy with heterogeneous epilepsy phenotypes. We genotyped 41 family members, including 21 affected individuals, to localize the gene causing epilepsy in a large family segregating an autosomal dominant form of GEFS+. A genomewide search examining 197 markers identified linkage of GEFS+ to chromosome 2, on the basis of an initial positive LOD score for marker D2S294 (Z=4.4, recombination fraction [θ] = 0). A total of 24 markers were tested on chromosome 2q, to define the smallest candidate region for GEFS+. The highest two-point LOD score (Zmax=5.29; θ=0) was obtained with marker D2S324. Critical recombination events mapped the GEFS+ gene to a 29-cM region flanked by markers D2S156 and D2S311, with the idiopathic generalized epilepsy locus thereby assigned to chromosome 2q23-q31. The existence of the heterogeneous epilepsy phenotypes in this kindred suggests that seizure predisposition determined by the GEFS+ gene on chromosome 2q could be modified by other genes and/or by environmental factors, to produce the different seizure types observed. PMID:10677328

  2. Fine scale mapping of the breast cancer 16q12 locus

    PubMed Central

    Udler, Miriam S.; Ahmed, Shahana; Healey, Catherine S.; Meyer, Kerstin; Struewing, Jeffrey; Maranian, Melanie; Kwon, Erika M.; Zhang, Jinghui; Tyrer, Jonathan; Karlins, Eric; Platte, Radka; Kalmyrzaev, Bolot; Dicks, Ed; Field, Helen; Maia, Ana-Teresa; Prathalingam, Radhika; Teschendorff, Andrew; McArthur, Stewart; Doody, David R.; Luben, Robert; Caldas, Carlos; Bernstein, Leslie; Kolonel, Laurence K.; Henderson, Brian E.; Wu, Anna H.; Le Marchand, Loic; Ursin, Giske; Press, Michael F.; Lindblom, Annika; Margolin, Sara; Shen, Chen-Yang; Yang, Show-Lin; Hsiung, Chia-Ni; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Ahn, Sei-Hyun; Malone, Kathleen E.; Haiman, Christopher A.; Pharoah, Paul D.; Ponder, Bruce A.J.; Ostrander, Elaine A.; Easton, Douglas F.; Dunning, Alison M.

    2010-01-01

    Recent genome-wide association studies have identified a breast cancer susceptibility locus on 16q12 with an unknown biological basis. We used a set of single nucleotide polymorphism (SNP) markers to generate a fine-scale map and narrowed the region of association to a 133 kb DNA segment containing the largely uncharacterized hypothetical gene LOC643714, a short intergenic region and the 5′ end of TOX3. Re-sequencing this segment in European subjects identified 293 common polymorphisms, including a set of 26 highly correlated candidate causal variants. By evaluation of these SNPs in five breast cancer case–control studies involving more than 23 000 subjects from populations of European and Southeast Asian ancestry, all but 14 variants could be excluded at odds of <1:100. Most of the remaining variants lie in the intergenic region, which exhibits evolutionary conservation and open chromatin conformation, consistent with a regulatory function. African-American case–control studies exhibit a different pattern of association suggestive of an additional causative variant. PMID:20332101

  3. Finer delineation and transcript map of the 7q31 locus deleted in myeloid neoplasms.

    PubMed

    Liang, Hong; Castro, Patricia D; Ma, Jin; Nagarajan, Lalitha

    2005-10-15

    Acquired complete and partial deletions of chromosome 7 are associated with several malignancies. In acute myelogenous leukemia (AML) and preleukemic myelodysplasia (MDS), loss of chromosome 7 portends a poor clinical outcome. The identity of a classical leukemia suppressor gene, however, has been elusive. Previously, we defined a candidate suppressor locus of approximately 6 Mb in the 7q31 interval. Here we report an island of retention of heterozygosity within this interval in a case of monosomy 7. Allelotyping of AML cell lines revealed that ML3 and HEL cells, karyotypically diploid for chromosome 7, are hemizygous for all the 7q31 loci, implicating loss of the wild type and duplication of the remaining chromosome 7. Based on the completed genomic sequence of chromosome 7, we have generated a transcript map of the critical region of loss (between the D7S525 and D7S2502 loci). Notably, a recently characterized tumor suppressor gene, DOCK4, and an evolutionarily conserved zinc finger gene, ZNF277, localize to this interval, head to head, within <0.5 kb of each other. Thus, the reagents generated in this study will be valuable in elucidating the role of loss of 7q31 loci in the pathogenesis of AML.

  4. Efficient network-guided multi-locus association mapping with graph cuts

    PubMed Central

    Azencott, Chloé-Agathe; Grimm, Dominik; Sugiyama, Mahito; Kawahara, Yoshinobu

    2013-01-01

    Motivation: As an increasing number of genome-wide association studies reveal the limitations of the attempt to explain phenotypic heritability by single genetic loci, there is a recent focus on associating complex phenotypes with sets of genetic loci. Although several methods for multi-locus mapping have been proposed, it is often unclear how to relate the detected loci to the growing knowledge about gene pathways and networks. The few methods that take biological pathways or networks into account are either restricted to investigating a limited number of predetermined sets of loci or do not scale to genome-wide settings. Results: We present SConES, a new efficient method to discover sets of genetic loci that are maximally associated with a phenotype while being connected in an underlying network. Our approach is based on a minimum cut reformulation of the problem of selecting features under sparsity and connectivity constraints, which can be solved exactly and rapidly. SConES outperforms state-of-the-art competitors in terms of runtime, scales to hundreds of thousands of genetic loci and exhibits higher power in detecting causal SNPs in simulation studies than other methods. On flowering time phenotypes and genotypes from Arabidopsis thaliana, SConES detects loci that enable accurate phenotype prediction and that are supported by the literature. Availability: Code is available at http://webdav.tuebingen.mpg.de/u/karsten/Forschung/scones/. Contact: chloe-agathe.azencott@tuebingen.mpg.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23812981

  5. A human melanoma metastasis-suppressor locus maps to 6q16.3-q23.

    PubMed

    Miele, M E; Jewett, M D; Goldberg, S F; Hyatt, D L; Morelli, C; Gualandi, F; Rimessi, P; Hicks, D J; Weissman, B E; Barbanti-Brodano, G; Welch, D R

    2000-05-15

    Loss, deletion or rearrangement along large portions of the long arm (q-arm) of chromosome 6 occurs in >80% of late-stage human melanomas, suggesting that genes controlling malignant characteristics are encoded there. Metastasis, but not tumorigenicity, was completely suppressed in the human melanoma cell line C8161 into which an additional intact chromosome 6 had been introduced by microcell-mediated chromosome transfer. Our objective was to refine the location of a putative metastasis suppressor gene. To do this, we transferred an intact (neo6) and a deletion variant [neo6qdel; neo6(del)(q16.3-q23)] of neomycin-tagged human chromosome 6 into metastatic C8161 subclone 9 (C8161.9) by MMCT. Single cell hybrid clones were selected in G-418 and isolated. Following verification that the hybrids retained the expected regions of chromosome 6 using a panel of polymorphic sequence-tagged sites, the hybrids were tested for tumorigenicity and metastasis in athymic mice. As reported previously, intact, normal chromosome 6 suppressed metastasis whether tumor cells were injected i.v. or into an orthotopic (i.e., intradermal) site. In contrast, metastasis was not suppressed in the neo6qdel hybrids. Tumorigenicity was unaffected in hybrids prepared with either chromosome 6 donor. These data strongly suggest that a human melanoma metastasis suppressor locus maps between 6q16.3-q23 ( approximately 40 cM).

  6. Molecular mapping of the C locus for presence of pungency in Capsicum.

    PubMed

    Blum, Eyal; Liu, Kede; Mazourek, Michael; Yoo, Eun Young; Jahn, Molly; Paran, Ilan

    2002-08-01

    Pungency owing to the presence of capsaicinoids is a unique character of pepper (Capsicum spp.). Capsaicinoids are produced in the placenta and it has long been known that a single dominant gene, C, is required for pungent genotypes to produce capsaicinoids. We mapped C to pepper chromosome 2 in a cross between a pungent Capsicum frutescens wild accession and a non-pungent Capsicum annuum bell pepper. This position confirmed results from earlier studies. The RFLP marker TG 205 cosegregated with C and two additional RFLP markers were also located within 1 cM. The recessive allele at the C locus is used in breeding programs around the world focused on very diverse germplasm, hence any of these tightly linked markers may be of value as potential sources of useful markers for marker-assisted selection. To demonstrate this point, we developed a PCR-based CAPS (cleaved amplified polymorphic sequence) marker linked to C using the sequence of the Capsicum fibrillin gene located 0.4 cM from C. The use of molecular markers for high-throughput screening for the c allele in pepper breeding programs is discussed.

  7. Fine Mapping of Ur-3, a Historically Important Rust Resistance Locus in Common Bean

    PubMed Central

    Hurtado-Gonzales, Oscar P.; Valentini, Giseli; Gilio, Thiago A. S.; Martins, Alexandre M.; Song, Qijian; Pastor-Corrales, Marcial A.

    2016-01-01

    Bean rust, caused by Uromyces appendiculatus, is a devastating disease of common bean (Phaseolus vulgaris) in the Americas and Africa. The historically important Ur-3 gene confers resistance to many races of the highly variable bean rust pathogen that overcome other rust resistance genes. Existing molecular markers tagging Ur-3 for use in marker-assisted selection produce false results. Here, we describe the fine mapping of the Ur-3 locus for the development of highly accurate markers linked to Ur-3. An F2 population from the cross Pinto 114 (susceptible) × Aurora (resistant with Ur-3) was evaluated for its reaction to four different races of U. appendiculatus. A bulked segregant analysis using the SNP chip BARCBEAN6K_3 placed the approximate location of Ur-3 in the lower arm of chromosome Pv11. Specific SSR and SNP markers and haplotype analysis of 18 sequenced bean varieties positioned Ur-3 in a 46.5 kb genomic region from 46.96 to 47.01 Mb on Pv11. We discovered in this region the SS68 KASP marker that was tightly linked to Ur-3. Validation of SS68 on a panel of 130 diverse common bean cultivars containing all known rust resistance genes revealed that SS68 was highly accurate and produced no false results. The SS68 marker will be of great value in pyramiding Ur-3 with other rust resistance genes. It will also significantly reduce time and labor associated with the current phenotypic detection of Ur-3. This is the first utilization of fine mapping to discover markers linked to rust resistance in common bean. PMID:28031244

  8. Mapping a novel locus for familial atrial fibrillation on chromosome 10p11-q21.

    PubMed

    Volders, Paul G A; Zhu, Qian; Timmermans, Carl; Eurlings, Petra M H; Su, Xiaoyan; Arens, Yvonne H; Li, Li; Jongbloed, Roselie J; Xia, Min; Rodriguez, Luz-Maria; Chen, Yi Han

    2007-04-01

    Atrial Fibrillation (AF), the most common cardiac arrhythmia, is a significant public health problem in the United States, affecting approximately 2.2 million Americans. Recently, several chromosomal loci and genes have been found to be associated with familial AF. However, in most other AF cases, the genetic basis is still poorly understood. The purpose of this study was to investigate the molecular basis of familial AF in a Dutch kindred group. We analyzed a four-generation Dutch family in which AF segregated as an autosomal dominant trait. After the exclusion of linkage to 10q22-24, 6q14-16, 5p13, KCNQ1, KCNE2, KCNJ2 and some ion-channel-associated candidate genes, a genome-wide linkage scan using 398 microsatellite markers was performed. Two-point logarithms of odds (LOD) scores >1 at recombination fraction [theta] = 0.00 and a haplotype segregating with the disorder were demonstrated only across regions of chromosome 10. Subsequent fine mapping gave a maximum two-point LOD score of 4.1982 at D10S568 at [theta] = 0.00. Distinct recombination in several individuals narrowed the shared region among all affected individuals to 16.4 cM on the Genethon map (flanking markers: D10S578 and D10S1652), which corresponds to chromosome 10p11-q21. Thirteen candidate genes residing in this region, which could be associated with AF, were screened. No mutation has been found in their coding regions including the intron splice regions. We identify a novel locus for AF on chromosome 10p11-q21, which provides further evidence of genetic heterogeneity in this arrhythmia.

  9. Fine mapping and chromosome walking towards the Ror1 locus in barley (Hordeum vulgare L.).

    PubMed

    Acevedo-Garcia, Johanna; Collins, Nicholas C; Ahmadinejad, Nahal; Ma, Lu; Houben, Andreas; Bednarek, Pawel; Benjdia, Mariam; Freialdenhoven, Andreas; Altmüller, Janine; Nürnberg, Peter; Reinhardt, Richard; Schulze-Lefert, Paul; Panstruga, Ralph

    2013-12-01

    The Ror1 gene was fine-mapped to the pericentric region of barley chromosome 1HL. Recessively inherited loss-of-function alleles of the barley (Hordeum vulgare) Mildew resistance locus o (Mlo) gene confer durable broad-spectrum disease resistance against the obligate biotrophic fungal powdery mildew pathogen Blumeria graminis f.sp. hordei. Previous genetic analyses revealed two barley genes, Ror1 and Ror2, that are Required for mlo-specified resistance and basal defence. While Ror2 was cloned and shown to encode a t-SNARE protein (syntaxin), the molecular nature or Ror1 remained elusive. Ror1 was previously mapped to the centromeric region of the long arm of barley chromosome 1H. Here, we narrowed the barley Ror1 interval to 0.18 cM and initiated a chromosome walk using barley yeast artificial chromosome (YAC) clones, next-generation DNA sequencing and fluorescence in situ hybridization. Two non-overlapping YAC contigs containing Ror1 flanking genes were identified. Despite a high degree of synteny observed between barley and the sequenced genomes of the grasses rice (Oryza sativa), Brachypodium distachyon and Sorghum bicolor across the wider chromosomal area, the genes in the YAC contigs showed extensive interspecific rearrangements in orientation and order. Consequently, the position of a Ror1 homolog in these species could not be precisely predicted, nor was a barley gene co-segregating with Ror1 identified. These factors have prevented the molecular identification of the Ror1 gene for the time being.

  10. Mapping of the Domestic Cat “SILVER” Coat Color Locus Identifies a Unique Genomic Location for Silver in Mammals

    PubMed Central

    David, Victor A.; Eizirik, Eduardo; Roelke, Melody E.; Ghaffari, Helya; O'Brien, Stephen J.

    2009-01-01

    The SILVER locus has been mapped in the domestic cat, identifying a unique genomic location distinct from that of any known reported gene associated with silver or hypopigmentation in mammals. A demonstrated lack of linkage to SILV, the strong candidate gene for silver, led to the initiation of a genome scan utilizing 2 pedigrees segregating for silver coat color. Linkage mapping defined a genomic region for SILVER as a 3.3-Mb region, (95.87–99.21 Mb) on chromosome D2, (peak logarithm of the odds = 10.5, θ = 0), which displays conserved synteny to a genomic interval between 118.58 and 121.85 Mb on chromosome 10 in the human genome. In the domestic cat, mutations at the SILVER locus suppress the development of pigment in the hair, but in contrast to other mammalian silver variants, there is an apparently greater influence on the production of pheomelanin than eumelanin pigment. The mapping of a novel locus for SILVER offers much promise in identifying a gene that may help elucidate aspects of pheomelanogenesis, a pathway that has been very elusive, and illustrates the promise of the cat genome project in increasing our understanding of basic biological processes of general relevance for mammals. PMID:19398491

  11. Molecular mapping and candidate gene analysis of a new epicuticular wax locus in sorghum (Sorghum bicolor L. Moench).

    PubMed

    Uttam, G Anurag; Praveen, M; Rao, Y Venkateswara; Tonapi, Vilas A; Madhusudhana, R

    2017-07-12

    A new epicuticular wax (bloom) locus has been identified and fine mapped to the 207.89 kb genomic region on chromosome 1. A putative candidate gene, Sobic.001G269200, annotated as GDSL-like lipase/acylhydrolase, is proposed as the most probable candidate gene involved in bloom synthesis/deposition. Deposition of epicuticular wax on plant aerial surface is one strategy that plants adapt to reduce non-transpiration water loss. Epicuticular wax (bloom)-less mutants in sorghum with their glossy phenotypes exhibit changes in the accumulation of epicuticular wax on leaf and culm surfaces. We report molecular mapping of a new sorghum locus, bloomless mutant (bm39), involved in epicuticular wax biosynthesis in sorghum. Inheritance studies involving a profusely bloom parent (BTx623) and a spontaneous bloomless mutant (RS647) indicated that the parents differed in a single gene for bloom synthesis. Bloomless was recessive to bloom deposition. Genetic mapping involving F2 and F7 mapping populations in diverse genetic backgrounds (BTx623 × RS647; 296A × RS647 and 27A × RS647) identified and validated the map location of bm39 to a region of 207.89 kb on chromosome 1. SSR markers, Sblm13 and Sblm16, flanked the bm39 locus to a map interval of 0.3 cM on either side. Nine candidate genes were identified, of which Sobic.001G269200 annotated for GDSL-like lipase/acylhydrolase is the most likely gene associated with epicuticular wax deposition. Gene expression analysis in parents, isogenic lines and sets of near isogenic lines also confirmed the reduced expression of the putative candidate gene. The study opens possibilities for a detailed molecular analysis of the gene, its role in epicuticular wax synthesis and deposition, and may help to understand its function in moisture stress tolerance and insect and pathogen resistance in sorghum.

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

    SciTech Connect

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

    1994-09-01

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

  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. A 2-Mb YAC/BAC-based physical map of the ovum mutant (Om) locus region on mouse chromosome 11.

    PubMed

    Cohen-Tannoudji, M; Vandormael-Pournin, S; Le Bras, S; Coumailleau, F; Babinet, C; Baldacci, P

    2000-09-15

    The embryonic lethal phenotype observed when DDK females are crossed with males from other strains results from a deleterious interaction between the egg cytoplasm and the paternal pronucleus soon after fertilization. We have previously mapped the Om locus responsible for this phenotype, called the DDK syndrome, to an approximately 2-cM region of chromosome 11. Here, we report the generation of a physical map of 28 yeast and bacterial artificial chromosome clones encompassing the entire genetic interval containing the Om locus. This contig, spanning approximately 2 Mb, was used to map precisely genes and genetic markers of the region. We determined the maximum physical interval for Om to be 1400 kb. In addition, 11 members of the Scya gene family were found to be organized into two clusters at the borders of the Om region. Two other genes (Rad51l3 and Schlafen 2) and one EST (D11Wsu78e) were also mapped in the Om region. This integrated map provides support for the identification of additional candidate genes for the DDK syndrome. Copyright 2000 Academic Press.

  15. Quantitative trait locus mapping with background control in genetic populations of clonal F1 and double cross.

    PubMed

    Zhang, Luyan; Li, Huihui; Ding, Junqiang; Wu, Jianyu; Wang, Jiankang

    2015-12-01

    In this study, we considered five categories of molecular markers in clonal F1 and double cross populations, based on the number of distinguishable alleles and the number of distinguishable genotypes at the marker locus. Using the completed linkage maps, incomplete and missing markers were imputed as fully informative markers in order to simplify the linkage mapping approaches of quantitative trait genes. Under the condition of fully informative markers, we demonstrated that dominance effect between the female and male parents in clonal F1 and double cross populations can cause the interactions between markers. We then developed an inclusive linear model that includes marker variables and marker interactions so as to completely control additive effects of the female and male parents, as well as the dominance effect between the female and male parents. The linear model was finally used for background control in inclusive composite interval mapping (ICIM) of quantitative trait locus (QTL). The efficiency of ICIM was demonstrated by extensive simulations and by comparisons with simple interval mapping, multiple-QTL models and composite interval mapping. Finally, ICIM was applied in one actual double cross population to identify QTL on days to silking in maize.

  16. Quantitative trait locus mapping with background control in genetic populations of clonal F1 and double cross

    PubMed Central

    Zhang, Luyan; Li, Huihui; Ding, Junqiang; Wu, Jianyu

    2015-01-01

    Abstract In this study, we considered five categories of molecular markers in clonal F1 and double cross populations, based on the number of distinguishable alleles and the number of distinguishable genotypes at the marker locus. Using the completed linkage maps, incomplete and missing markers were imputed as fully informative markers in order to simplify the linkage mapping approaches of quantitative trait genes. Under the condition of fully informative markers, we demonstrated that dominance effect between the female and male parents in clonal F1 and double cross populations can cause the interactions between markers. We then developed an inclusive linear model that includes marker variables and marker interactions so as to completely control additive effects of the female and male parents, as well as the dominance effect between the female and male parents. The linear model was finally used for background control in inclusive composite interval mapping (ICIM) of quantitative trait locus (QTL). The efficiency of ICIM was demonstrated by extensive simulations and by comparisons with simple interval mapping, multiple‐QTL models and composite interval mapping. Finally, ICIM was applied in one actual double cross population to identify QTL on days to silking in maize. PMID:25881980

  17. Use of genetic and physical mapping to locate the spinal muscular atrophy locus between two new highly polymorphic DNA markers

    SciTech Connect

    Clermont, O.; Burlet, P.; Burglen, L.; Lefebvre, S.; Pascal, F.; McPherson, J.; Wasmuth, J.J.; Cohen, D.; Le Paslier, D.; Weissenbach, J.

    1994-04-01

    The gene for autosomal recessive forms of spinal muscular atrophy (SMA) has recently been mapped to chromosome 5q13, within a 4-cM region between the blocks D5S465/D5S125 and MAP-1B/D5S112. The authors identified two new highly polymorphic microsatellite DNA markers - namely, AFM265wf5 (D5S629) and AFM281yh9 (D5S637) - which are the closest markers to the SMA locus. Multilocus analysis by the location-score method was used to establish the best estimate of the SMA gene location. The data suggest that the most likely location for SMA is between locus D5S629 and the block D5S637/D5S351/MAP-1B/D5S112/D5S357. Genetic analysis of inbred SMA families, based on homozygosity by descent and physical mapping using meta-YACs, gave additional information for the loci order as follows: cen-D5S6-D5S125/D5S465-D5S435-D5S629-SMA-D5S637-D5S351-MAP-1B/D5S112-D5S357-D5S39-tel. These data give the direction for bidirectional walking in order to clone this interval and isolate the SMA gene. 16 refs., 4 figs., 2 tabs.

  18. 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.

  19. Mapping the sex determination locus in the Atlantic halibut (Hippoglossus hippoglossus) using RAD sequencing

    PubMed Central

    2013-01-01

    Background Atlantic halibut (Hippoglossus hippoglossus) is a high-value, niche market species for cold-water marine aquaculture. Production of monosex female stocks is desirable in commercial production since females grow faster and mature later than males. Understanding the sex determination mechanism and developing sex-associated markers will shorten the time for the development of monosex female production, thus decreasing the costs of farming. Results Halibut juveniles were masculinised with 17 α-methyldihydrotestosterone (MDHT) and grown to maturity. Progeny groups from four treated males were reared and sexed. Two of these groups (n = 26 and 70) consisted of only females, while the other two (n = 30 and 71) contained balanced sex ratios (50% and 48% females respectively). DNA from parents and offspring from the two mixed-sex families were used as a template for Restriction-site Associated DNA (RAD) sequencing. The 648 million raw reads produced 90,105 unique RAD-tags. A linkage map was constructed based on 5703 Single Nucleotide Polymorphism (SNP) markers and 7 microsatellites consisting of 24 linkage groups, which corresponds to the number of chromosome pairs in this species. A major sex determining locus was mapped to linkage group 13 in both families. Assays for 10 SNPs with significant association with phenotypic sex were tested in both population data and in 3 additional families. Using a variety of machine-learning algorithms 97% correct classification could be obtained with the 3% of errors being phenotypic males predicted to be females. Conclusion Altogether our findings support the hypothesis that the Atlantic halibut has an XX/XY sex determination system. Assays are described for sex-associated DNA markers developed from the RAD sequencing analysis to fast track progeny testing and implement monosex female halibut production for an immediate improvement in productivity. These should also help to speed up the inclusion of neomales derived

  20. High-resolution linkage map in the proximity of the host resistance locus Cmv1

    SciTech Connect

    Depatie, C.; Muise, E.; Gros, P.

    1997-01-15

    The mouse chromosome 6 locus Cmv1 controls replication of mouse Cytomegalovirus (MCMV) in the spleen of the infected host. In our effort to clone Cmv1, we have constructed a high-resolution genetic linkage map in the proximity of the gene. For this, a total of 45 DNA markers corresponding to either cloned genes or microsatellites were mapped within a 7.9-cM interval overlapping the Cmv1 region. We have followed the cosegregation of these markers with respect to Cmv1 in a total of 2248 backcross mice from a preexisting interspecific backcross panel of 281 (Mus spretus X C57BL/6J)F1 X C57BL/6J and 2 novel panels of 989 (A/J X C57BL6)F1 X A/J and 978 (BALB/c X C57BL/6J)F1 X BALB/c segregating Cmv1. Combined pedigree analysis allowed us to determine the following gene order and intergene distances (in cM) on the distal region of mouse chromosome 6: D6Mit216-(1.9)-D6Mit336-(2.2)-D6Mit218-(1.0)-D6Mit52-(0.5)-D6Mit194-(0.2)-Nkrp1/D6Mit61/135/257/289/338-(0.4)-Cmv1/Ly49A/D6Mit370-(0.3)-Prp/Kap/D6Mit13/111/219-(0.3)-Tel/D6Mit374/290/220/196/195/110-(1.1)-D6Mit25. Therefore, the minimal genetic interval for Cmv1 of 0.7 cM is defined by 13 tightly linked markers including 2 markers, Ly49A and D6Mit370, that did not show recombination with Cmv1 in 1967 meioses analyzed; the proximal limit of the Cmv1 domain was defined by 8 crossovers between Nkrp1/D6Mit61/135/257/289/338 and Cmv1/Ly49A/D6Mit370, and the distal limit was defined by 5 crossovers between Cmv1/Ly49A/D6Mit370 and Prp/Kap/D6Mit13/111/219. This work demonstrates tight linkage between Cmv1 and genes from the natural killer complex (NKC), such as Nkrp1 and Ly49A suggesting that Cmv1 may represent an NK cell recognition structure encoded in the NKC region. 54 refs., 4 figs., 2 tabs.

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

    PubMed

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

    1996-08-01

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

  2. 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

  3. A maize map standard with sequenced core markers, grass genome reference points and 932 expressed sequence tagged sites (ESTs) in a 1736-locus map.

    PubMed Central

    Davis, G L; McMullen, M D; Baysdorfer, C; Musket, T; Grant, D; Staebell, M; Xu, G; Polacco, M; Koster, L; Melia-Hancock, S; Houchins, K; Chao, S; Coe, E H

    1999-01-01

    We have constructed a 1736-locus maize genome map containing1156 loci probed by cDNAs, 545 probed by random genomic clones, 16 by simple sequence repeats (SSRs), 14 by isozymes, and 5 by anonymous clones. Sequence information is available for 56% of the loci with 66% of the sequenced loci assigned functions. A total of 596 new ESTs were mapped from a B73 library of 5-wk-old shoots. The map contains 237 loci probed by barley, oat, wheat, rice, or tripsacum clones, which serve as grass genome reference points in comparisons between maize and other grass maps. Ninety core markers selected for low copy number, high polymorphism, and even spacing along the chromosome delineate the 100 bins on the map. The average bin size is 17 cM. Use of bin assignments enables comparison among different maize mapping populations and experiments including those involving cytogenetic stocks, mutants, or quantitative trait loci. Integration of nonmaize markers in the map extends the resources available for gene discovery beyond the boundaries of maize mapping information into the expanse of map, sequence, and phenotype information from other grass species. This map provides a foundation for numerous basic and applied investigations including studies of gene organization, gene and genome evolution, targeted cloning, and dissection of complex traits. PMID:10388831

  4. A maize map standard with sequenced core markers, grass genome reference points and 932 expressed sequence tagged sites (ESTs) in a 1736-locus map.

    PubMed

    Davis, G L; McMullen, M D; Baysdorfer, C; Musket, T; Grant, D; Staebell, M; Xu, G; Polacco, M; Koster, L; Melia-Hancock, S; Houchins, K; Chao, S; Coe, E H

    1999-07-01

    We have constructed a 1736-locus maize genome map containing1156 loci probed by cDNAs, 545 probed by random genomic clones, 16 by simple sequence repeats (SSRs), 14 by isozymes, and 5 by anonymous clones. Sequence information is available for 56% of the loci with 66% of the sequenced loci assigned functions. A total of 596 new ESTs were mapped from a B73 library of 5-wk-old shoots. The map contains 237 loci probed by barley, oat, wheat, rice, or tripsacum clones, which serve as grass genome reference points in comparisons between maize and other grass maps. Ninety core markers selected for low copy number, high polymorphism, and even spacing along the chromosome delineate the 100 bins on the map. The average bin size is 17 cM. Use of bin assignments enables comparison among different maize mapping populations and experiments including those involving cytogenetic stocks, mutants, or quantitative trait loci. Integration of nonmaize markers in the map extends the resources available for gene discovery beyond the boundaries of maize mapping information into the expanse of map, sequence, and phenotype information from other grass species. This map provides a foundation for numerous basic and applied investigations including studies of gene organization, gene and genome evolution, targeted cloning, and dissection of complex traits.

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

    PubMed

    Bachmanov, A A; Li, X; Li, S; Neira, M; Beauchamp, G K; Azen, E A

    2001-09-01

    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' (Soa(a)), 'nontaster' (Soa(b)), and 'demitaster' (Soa(c)) 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-Soa(b), B6.SW-Soa(a), and C3.SW-Soa(a/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 an approximately 1-cM (3.3-4.9 Mb) region including the Prp locus.

  6. A high-resolution linkage map of the vicinity of the rice submergence tolerance locus Sub1.

    PubMed

    Xu, K; Xu, X; Ronald, P C; Mackill, D J

    2000-05-01

    Resistance to submergence stress is an important breeding objective in areas where rice cultivars are subjected to complete inundation for a week or more. The present study was conducted to develop a high-resolution map of the region surrounding the submergence tolerance gene Sub1 in rice, which derives from the Indian cultivar FR13A. Submergence screening of 8-day-old plants of F3 families kept for 14 days submerged in 60 cm of water allowed an accurate classification of Sub1 phenotypes. Bulked segregant analysis was used to identify AFLP markers linked to Sub1. A population of 2950 F2 plants segregating for Sub1 was screened with two RFLP markers flanking the Sub1 locus, 2.4 and 4.9 cM away. Submergence tolerance was measured in the recombinant plants, and AFLP markers closely linked to Sub1 were mapped. Two AFLP markers cosegregated with Sub1 in this large population, and other markers were localized within 0.2 cM of Sub1. The high-resolution map should serve as the basis for map-based cloning of this important locus, as it will permit the identification of BAC clones spanning the region.

  7. Genome Wide Single Locus Single Trait, Multi-Locus and Multi-Trait Association Mapping for Some Important Agronomic Traits in Common Wheat (T. aestivum L.)

    PubMed Central

    Jaiswal, Vandana; Gahlaut, Vijay; Meher, Prabina Kumar; Mir, Reyazul Rouf; Jaiswal, Jai Prakash; Rao, Atmakuri Ramakrishna; Balyan, Harindra Singh; Gupta, Pushpendra Kumar

    2016-01-01

    Genome wide association study (GWAS) was conducted for 14 agronomic traits in wheat following widely used single locus single trait (SLST) approach, and two recent approaches viz. multi locus mixed model (MLMM), and multi-trait mixed model (MTMM). Association panel consisted of 230 diverse Indian bread wheat cultivars (released during 1910–2006 for commercial cultivation in different agro-climatic regions in India). Three years phenotypic data for 14 traits and genotyping data for 250 SSR markers (distributed across all the 21 wheat chromosomes) was utilized for GWAS. Using SLST, as many as 213 MTAs (p ≤ 0.05, 129 SSRs) were identified for 14 traits, however, only 10 MTAs (~9%; 10 out of 123 MTAs) qualified FDR criteria; these MTAs did not show any linkage drag. Interestingly, these genomic regions were coincident with the genomic regions that were already known to harbor QTLs for same or related agronomic traits. Using MLMM and MTMM, many more QTLs and markers were identified; 22 MTAs (19 QTLs, 21 markers) using MLMM, and 58 MTAs (29 QTLs, 40 markers) using MTMM were identified. In addition, 63 epistatic QTLs were also identified for 13 of the 14 traits, flag leaf length (FLL) being the only exception. Clearly, the power of association mapping improved due to MLMM and MTMM analyses. The epistatic interactions detected during the present study also provided better insight into genetic architecture of the 14 traits that were examined during the present study. Following eight wheat genotypes carried desirable alleles of QTLs for one or more traits, WH542, NI345, NI170, Sharbati Sonora, A90, HW1085, HYB11, and DWR39 (Pragati). These genotypes and the markers associated with important QTLs for major traits can be used in wheat improvement programs either using marker-assisted recurrent selection (MARS) or pseudo-backcrossing method. PMID:27441835

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

    PubMed Central

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

    2016-01-01

    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

  9. Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

    PubMed

    Painter, Jodie N; O'Mara, Tracy A; Batra, Jyotsna; Cheng, Timothy; Lose, Felicity A; Dennis, Joe; Michailidou, Kyriaki; Tyrer, Jonathan P; Ahmed, Shahana; Ferguson, Kaltin; Healey, Catherine S; Kaufmann, Susanne; Hillman, Kristine M; Walpole, Carina; Moya, Leire; Pollock, Pamela; Jones, Angela; Howarth, Kimberley; Martin, Lynn; Gorman, Maggie; Hodgson, Shirley; De Polanco, Ma Magdalena Echeverry; Sans, Monica; Carracedo, Angel; Castellvi-Bel, Sergi; Rojas-Martinez, Augusto; Santos, Erika; Teixeira, Manuel R; Carvajal-Carmona, Luis; Shu, Xiao-Ou; Long, Jirong; Zheng, Wei; Xiang, Yong-Bing; Montgomery, Grant W; Webb, Penelope M; Scott, Rodney J; McEvoy, Mark; Attia, John; Holliday, Elizabeth; Martin, Nicholas G; Nyholt, Dale R; Henders, Anjali K; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Renner, Stefan P; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo; Lambrechts, Diether; Coenegrachts, Lieve; Schrauwen, Stefanie; Amant, Frederic; Winterhoff, Boris; Dowdy, Sean C; Goode, Ellen L; Teoman, Attila; Salvesen, Helga B; Trovik, Jone; Njolstad, Tormund S; Werner, Henrica M J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Tzortzatos, Gerasimos; Mints, Miriam; Tham, Emma; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Jingmei; Hopper, John L; Southey, Melissa C; Ekici, Arif B; Ruebner, Matthias; Johnson, Nicola; Peto, Julian; Burwinkel, Barbara; Marme, Frederik; Brenner, Hermann; Dieffenbach, Aida K; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Depreeuw, Jeroen; Moisse, Matthieu; Chang-Claude, Jenny; Rudolph, Anja; Couch, Fergus J; Olson, Janet E; Giles, Graham G; Bruinsma, Fiona; Cunningham, Julie M; Fridley, Brooke L; Børresen-Dale, Anne-Lise; Kristensen, Vessela N; Cox, Angela; Swerdlow, Anthony J; Orr, Nicholas; Bolla, Manjeet K; Wang, Qin; Weber, Rachel Palmieri; Chen, Zhihua; Shah, Mitul; French, Juliet D; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Edwards, Stacey L; Thompson, Deborah J; Spurdle, Amanda B

    2015-03-01

    Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk

    PubMed Central

    Painter, Jodie N.; O'Mara, Tracy A.; Batra, Jyotsna; Cheng, Timothy; Lose, Felicity A.; Dennis, Joe; Michailidou, Kyriaki; Tyrer, Jonathan P.; Ahmed, Shahana; Ferguson, Kaltin; Healey, Catherine S.; Kaufmann, Susanne; Hillman, Kristine M.; Walpole, Carina; Moya, Leire; Pollock, Pamela; Jones, Angela; Howarth, Kimberley; Martin, Lynn; Gorman, Maggie; Hodgson, Shirley; De Polanco, Ma. Magdalena Echeverry; Sans, Monica; Carracedo, Angel; Castellvi-Bel, Sergi; Rojas-Martinez, Augusto; Santos, Erika; Teixeira, Manuel R.; Carvajal-Carmona, Luis; Shu, Xiao-Ou; Long, Jirong; Zheng, Wei; Xiang, Yong-Bing; Montgomery, Grant W.; Webb, Penelope M.; Scott, Rodney J.; McEvoy, Mark; Attia, John; Holliday, Elizabeth; Martin, Nicholas G.; Nyholt, Dale R.; Henders, Anjali K.; Fasching, Peter A.; Hein, Alexander; Beckmann, Matthias W.; Renner, Stefan P.; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo; Lambrechts, Diether; Coenegrachts, Lieve; Schrauwen, Stefanie; Amant, Frederic; Winterhoff, Boris; Dowdy, Sean C.; Goode, Ellen L.; Teoman, Attila; Salvesen, Helga B.; Trovik, Jone; Njolstad, Tormund S.; Werner, Henrica M.J.; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Tzortzatos, Gerasimos; Mints, Miriam; Tham, Emma; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Jingmei; Hopper, John L.; Southey, Melissa C.; Ekici, Arif B.; Ruebner, Matthias; Johnson, Nicola; Peto, Julian; Burwinkel, Barbara; Marme, Frederik; Brenner, Hermann; Dieffenbach, Aida K.; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Depreeuw, Jeroen; Moisse, Matthieu; Chang-Claude, Jenny; Rudolph, Anja; Couch, Fergus J.; Olson, Janet E.; Giles, Graham G.; Bruinsma, Fiona; Cunningham, Julie M.; Fridley, Brooke L.; Børresen-Dale, Anne-Lise; Kristensen, Vessela N.; Cox, Angela; Swerdlow, Anthony J.; Orr, Nicholas; Bolla, Manjeet K.; Wang, Qin; Weber, Rachel Palmieri; Chen, Zhihua; Shah, Mitul; French, Juliet D.; Pharoah, Paul D.P.; Dunning, Alison M.; Tomlinson, Ian; Easton, Douglas F.; Edwards, Stacey L.; Thompson, Deborah J.; Spurdle, Amanda B.

    2015-01-01

    Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10−14, odds ratio = 0.86, 95% confidence interval = 0.82–0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression. PMID:25378557

  11. Fine mapping and identification of a candidate gene for a major locus controlling maturity date in peach.

    PubMed

    Pirona, Raul; Eduardo, Iban; Pacheco, Igor; Da Silva Linge, Cassia; Miculan, Mara; Verde, Ignazio; Tartarini, Stefano; Dondini, Luca; Pea, Giorgio; Bassi, Daniele; Rossini, Laura

    2013-10-22

    Maturity date (MD) is a crucial factor for marketing of fresh fruit, especially those with limited shelf-life such as peach (Prunus persica L. Batsch): selection of several cultivars with differing MD would be advantageous to cover and extend the marketing season. Aims of this work were the fine mapping and identification of candidate genes for the major maturity date locus previously identified on peach linkage group 4. To improve genetic resolution of the target locus two F2 populations derived from the crosses Contender x Ambra (CxA, 306 individuals) and PI91459 (NJ Weeping) x Bounty (WxBy, 103 individuals) were genotyped with the Sequenom and 9K Illumina Peach Chip SNP platforms, respectively. Recombinant individuals from the WxBy F2 population allowed the localisation of maturity date locus to a 220 kb region of the peach genome. Among the 25 annotated genes within this interval, functional classification identified ppa007577m and ppa008301m as the most likely candidates, both encoding transcription factors of the NAC (NAM/ATAF1, 2/CUC2) family. Re-sequencing of the four parents and comparison with the reference genome sequence uncovered a deletion of 232 bp in the upstream region of ppa007577m that is homozygous in NJ Weeping and heterozygous in Ambra, Bounty and the WxBy F1 parent. However, this variation did not segregate in the CxA F2 population being the CxA F1 parent homozygous for the reference allele. The second gene was thus examined as a candidate for maturity date. Re-sequencing of ppa008301m, showed an in-frame insertion of 9 bp in the last exon that co-segregated with the maturity date locus in both CxA and WxBy F2 populations. Using two different segregating populations, the map position of the maturity date locus was refined from 3.56 Mb to 220 kb. A sequence variant in the NAC gene ppa008301m was shown to co-segregate with the maturity date locus, suggesting this gene as a candidate controlling ripening time in peach. If confirmed on other

  12. Fine mapping and identification of a candidate gene for a major locus controlling maturity date in peach

    PubMed Central

    2013-01-01

    Background Maturity date (MD) is a crucial factor for marketing of fresh fruit, especially those with limited shelf-life such as peach (Prunus persica L. Batsch): selection of several cultivars with differing MD would be advantageous to cover and extend the marketing season. Aims of this work were the fine mapping and identification of candidate genes for the major maturity date locus previously identified on peach linkage group 4. To improve genetic resolution of the target locus two F2 populations derived from the crosses Contender x Ambra (CxA, 306 individuals) and PI91459 (NJ Weeping) x Bounty (WxBy, 103 individuals) were genotyped with the Sequenom and 9K Illumina Peach Chip SNP platforms, respectively. Results Recombinant individuals from the WxBy F2 population allowed the localisation of maturity date locus to a 220 kb region of the peach genome. Among the 25 annotated genes within this interval, functional classification identified ppa007577m and ppa008301m as the most likely candidates, both encoding transcription factors of the NAC (NAM/ATAF1, 2/CUC2) family. Re-sequencing of the four parents and comparison with the reference genome sequence uncovered a deletion of 232 bp in the upstream region of ppa007577m that is homozygous in NJ Weeping and heterozygous in Ambra, Bounty and the WxBy F1 parent. However, this variation did not segregate in the CxA F2 population being the CxA F1 parent homozygous for the reference allele. The second gene was thus examined as a candidate for maturity date. Re-sequencing of ppa008301m, showed an in-frame insertion of 9 bp in the last exon that co-segregated with the maturity date locus in both CxA and WxBy F2 populations. Conclusions Using two different segregating populations, the map position of the maturity date locus was refined from 3.56 Mb to 220 kb. A sequence variant in the NAC gene ppa008301m was shown to co-segregate with the maturity date locus, suggesting this gene as a candidate controlling ripening time in

  13. Construction of physical maps of the Hor1 locus of two barley cultivars by pulsed field gel electrophoresis.

    PubMed

    Siedler, H; Graner, A

    1991-04-01

    In order to construct a physical map of the Hor1 locus of barley (Hordeum vulgare) high molecular weight DNA was prepared from leaf mesophyll protoplasts. Seventeen different restriction endonucleases containing CpG or CpXpG motifs in their recognition sequences were tested and ten proved useful for the generation of high molecular weight DNA fragments. Physical maps of the Hor1 region of the barley cultivars IGRI and FRANKA spanning a distance of 370 and 430 kb respectively were constructed. The maps include sites of nine restriction endonucleases in IGRI and of eight in FRANKA. The maximal extent of the Hor1 locus could be limited to a 135 kb DNA fragment occurring in both cultivars. The differences in arrangement of restriction sites and in fragment lengths reveal major differences in the Hor1 flanking region in the two cultivars. The location of a CpG island, however, is highly conserved in both cultivars and reflects similarities to the organization of mammalian genomes.

  14. 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.

  15. Meiotic breakpoint mapping of a proposed X linked visual loss susceptibility locus in Leber's hereditary optic neuropathy.

    PubMed Central

    Handoko, H Y; Wirapati, P J; Sudoyo, H A; Sitepu, M; Marzuki, S

    1998-01-01

    Leber's hereditary optic neuropathy (LHON) is a maternally inherited degenerative disorder characterised by an acute or subacute optic nerve degeneration resulting in visual failure. Mitochondrial DNA mutations have been reported and a nuclear modifier gene(s) on the X chromosome is thought to play an important role in the onset of this disorder. We analysed a LHON family with a novel and more accurate approach using 27 X chromosomal microsatellite markers. Meiotic breakpoint mapping and two point lod score did not point to any particular area on the X chromosome which might contain the X susceptibility locus. PMID:9719375

  16. A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.

    PubMed Central

    Varret, M; Rabès, J P; Saint-Jore, B; Cenarro, A; Marinoni, J C; Civeira, F; Devillers, M; Krempf, M; Coulon, M; Thiart, R; Kotze, M J; Schmidt, H; Buzzi, J C; Kostner, G M; Bertolini, S; Pocovi, M; Rosa, A; Farnier, M; Martinez, M; Junien, C; Boileau, C

    1999-01-01

    Autosomal dominant hypercholesterolemia (ADH), one of the most frequent hereditary disorders, is characterized by an isolated elevation of LDL particles that leads to premature mortality from cardiovascular complications. It is generally assumed that mutations in the LDLR and APOB genes account for ADH. We identified one large French pedigree (HC2) and 12 additional white families with ADH in which we excluded linkage to the LDLR and APOB, implicating a new locus we named "FH3." A LOD score of 3.13 at a recombination fraction of 0 was obtained at markers D1S2892 and D1S2722. We localized the FH3 locus to a 9-cM interval at 1p34.1-p32. We tested four regional markers in another set of 12 ADH families. Positive LOD scores were obtained in three pedigrees, whereas linkage was excluded in the others. Heterogeneity tests indicated linkage to FH3 in approximately 27% of these non-LDLR/non-APOB ADH families and implied a fourth locus. Radiation hybrid mapping located four candidate genes at 1p34.1-p32, outside the critical region, showing no identity with FH3. Our results show that ADH is genetically more heterogeneous than conventionally accepted. PMID:10205269

  17. A locus for axonal motor-sensory neuropathy with deafness and mental retardation maps to Xq24-q26

    SciTech Connect

    Priest, J.M.; Nouri, N.; Keats, B.J.B.

    1995-09-20

    DNA markers on the X chromosome were used to map the locus for an unusual form of X-linked recessive hereditary motor and sensory neuropathy with associated deafness and mental retardation in a three-generation family that was originally reported by Towchock et al. This family included seven affected males, three obligate carrier females, and four unaffected males. The patients were severely affected within the first few years of life with distal weakness, muscle atrophy, sensory loss, areflexia, pes cavus, and hammer toes. Five of the seven affected males showed associated deafness, and three of these five individuals also presented with mental retardation or social development delay. Motor nerve conduction velocitites in affected males were normal to mildly delayed, and sensory conduction was markedly abnormal. Heterozygous females were asymptomatic. Close linkage to the Xg blood group locus (Xp22) and the PGK locus (Xq13) was previously excluded in this family, while weak linkage of the disease gene to DXYS1 (Xq21.3) was suggested. Our current linkage studies and haplotype analysis of 19 microsatellite markers on the long arm of the X chromosome demonstrate that DXS425 (Xq24) and HPRT (Xq26.1) are flanking markers and that the disease gene is closely linked to the markers DSX1122, DXS994, DXS737, DXS100, DXS1206, and DXS1047. 27 refs., 1 fig., 2 tabs.

  18. The autosomal dominant familial exudative vitreoretinopathy locus maps on 11q and is closely linked to D11S533

    SciTech Connect

    Li, Yuen Zhejiang Medical Univ., Hangzhou ); Schwinger, D.; Gal, A. ); Mueller, B. ); Fuhrmann, C.; Laqua, H. ); Humphries, P.

    1992-10-01

    Autosomal dominant familial exudative vitreoretinopathy (adFEVR) is a hereditary disorder characterized by the incomplete vascularization of the peripheral retina. The primary biochemical defect in adFEVR is unknown. The adFEVR locus has tentatively been assigned to 11q by linkage studies. The authors report the results of an extended multipoint linkage analysis of two families with adFEVR by using five markers (INT2, D11S533, D11S527, D11S35, and CD3D) from 11q13-q23. Pairwise linkage data obtained in the two families were rather similar and hence have not provided evidence for genetic heterogeneity. The highest compiled two-point lod score (3.67, at a recombination fraction of .07) was obtained for the disease locus versus D11S533. Multipoint analyses showed that the adFEVR locus maps most likely, with a maximum location score of over 20, between D11S533/D11S526 and D11S35, at recombination rates of .147 and .104, respectively. Close linkage without recombination (maximum lod score 11.26) has been found between D11S533 and D11S526. 15 refs., 3 figs., 4 tabs.

  19. Molecular Mapping of D₁, D₂ and ms5 Revealed Linkage between the Cotyledon Color Locus D₂ and the Male-Sterile Locus ms5 in Soybean.

    PubMed

    Ott, Alina; Yang, Yang; Bhattacharyya, Madan; Horner, Harry T; Palmer, Reid G; Sandhu, Devinder

    2013-07-05

    In soybean, genic male sterility can be utilized as a tool to develop hybrid seed. Several male-sterile, female-fertile mutants have been identified in soybean. The male-sterile, female-fertile ms5 mutant was selected after fast neutron irradiation. Male-sterility due to ms5 was associated with the "stay-green" cotyledon color mutation. The cotyledon color trait in soybean is controlled by two loci, D₁ and D₂. Association between cotyledon color and male-sterility can be instrumental in early phenotypic selection of sterility for hybrid seed production. The use of such selection methods saves time, money, and space, as fewer seeds need to be planted and screened for sterility. The objectives of this study were to compare anther development between male-fertile and male-sterile plants, to investigate the possible linkages among the Ms5, D₁ and D₂ loci, and to determine if any of the d₁ or d₂ mutations can be applied in hybrid seed production. The cytological analysis during anther development displayed optically clear, disintegrating microspores and enlarged, engorged pollen in the male-sterile, female-fertile ms5ms5 plants, a common characteristic of male-sterile mutants. The D₁ locus was mapped to molecular linkage group (MLG) D1a and was flanked by Satt408 and BARCSOYSSR_01_1622. The ms5 and D₂ loci were mapped to MLG B1 with a genetic distance ~12.8 cM between them. These results suggest that use of the d₂ mutant in the selection of male-sterile line may attenuate the cost hybrid seed production in soybean.

  20. PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6.

    PubMed

    Oparina, Nina Y; Delgado-Vega, Angelica M; Martinez-Bueno, Manuel; Magro-Checa, César; Fernández, Concepción; Castro, Rafaela Ortega; Pons-Estel, Bernardo A; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Witte, Torsten; Lauwerys, Bernard R; Endreffy, Emoke; Kovács, László; Escudero, Alejandro; López-Pedrera, Chary; Vasconcelos, Carlos; da Silva, Berta Martins; Frostegård, Johan; Truedsson, Lennart; Martin, Javier; Raya, Enrique; Ortego-Centeno, Norberto; de Los Angeles Aguirre, Maria; de Ramón Garrido, Enrique; Palma, María-Jesús Castillo; Alarcon-Riquelme, Marta E; Kozyrev, Sergey V

    2015-03-01

    To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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

    SciTech Connect

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

    1993-07-01

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

  2. Genetic mapping of human heart-skeletal muscle adenine nucleotide translocator and its relationship to the facioscapulohumeral muscular dystrophy locus

    SciTech Connect

    Haraguchi, Y.; Chung, A.B.; Torroni, A.; Stepien, G.; Shoffner, J.M.; Costigan, D.A.; Polak, M.; Wasmuth, J.J.; Altherr, M.R.; Winokur, S.T.

    1993-05-01

    The mitochondrial heart-skeletal muscle adenine nucleotide translocator (ANT1) was regionally mapped to 4q35-qter using somatic cell hybrids containing deleted chromosome 4. The regional location was further refined through family studies using ANT1 intron and promoter nucleotide polymorphisms recognized by the restriction endonucleases MboII, NdeI, and HaeIII. Two alleles were found, each at a frequency of 0.5. The ANT1 locus was found to be closely linked to D4S139, D4S171, and the dominant skeletal muscle disease locus facioscapulohumeral muscular dystrophy (FSHD). A crossover that separated D4S171 and ANT1 from D4S139 was found. Since previous studies have established the chromosome 4 map order as centromere-D4S171-D4S139-FSHD, it was concluded that ANT1 is located on the side of D4S139, that is opposite from FSHD. This conclusion was confirmed by sequencing the exons and analyzing the transcripts of ANT1 from several FSHD patients and finding no evidence of aberration. 35 refs., 5 figs., 1 tab.

  3. Fine Mapping of a Grain-Weight Quantitative Trait Locus in the Pericentromeric Region of Rice Chromosome 3

    PubMed Central

    Li, Jiming; Thomson, Michael; McCouch, Susan R.

    2004-01-01

    As the basis for fine mapping of a grain-weight QTL, gw3.1, a set of near isogenic lines (NILs), was developed from an Oryza sativa, cv. Jefferson × O. rufipogon (IRGC105491) population based on five generations of backcrossing and seven generations of selfing. Despite the use of an interspecific cross for mapping and the pericentromeric location of the QTL, we observed no suppression of recombination and have been able to narrow down the location of the gene underlying this QTL to a 93.8-kb region. The locus was associated with transgressive variation for grain size and grain weight in this population and features prominently in many other inter- and intraspecific crosses of rice. The phenotype was difficult to evaluate due to the large amount of variance in size and weight among grains on a panicle and between grains on primary and secondary panicles, underscoring the value of using multiple approaches to phenotyping, including extreme sampling and NIL group-mean comparisons. The fact that a QTL for kernel size has also been identified in a homeologous region of maize chromosome 1 suggests that this locus, in which the dominant O. rufipogon allele confers small seed size, may be associated with domestication in cereals. PMID:15611185

  4. Mapping the Anthocyaninless (anl) Locus in Rapid-Cycling Brassica rapa (RBr) to Linkage Group R9

    PubMed Central

    Burdzinski, Carrie; Wendell, Douglas L

    2007-01-01

    Background Anthocyanins are flavonoid pigments that are responsible for purple coloration in the stems and leaves of a variety of plant species. Anthocyaninless (anl) mutants of Brassica rapa fail to produce anthocyanin pigments. In rapid-cycling Brassica rapa, also known as Wisconsin Fast Plants, the anthocyaninless trait, also called non-purple stem, is widely used as a model recessive trait for teaching genetics. Although anthocyanin genes have been mapped in other plants such as Arabidopsis thaliana, the anl locus has not been mapped in any Brassica species. Results We tested primer pairs known to amplify microsatellites in Brassicas and identified 37 that amplified a product in rapid-cycling Brassica rapa. We then developed three-generation pedigrees to assess linkage between the microsatellite markers and anl. 22 of the markers that we tested were polymorphic in our crosses. Based on 177 F2 offspring, we identified three markers linked to anl with LOD scores ≥ 5.0, forming a linkage group spanning 46.9 cM. Because one of these markers has been assigned to a known B. rapa linkage group, we can now assign the anl locus to B. rapa linkage group R9. Conclusion This study is the first to identify the chromosomal location of an anthocyanin pigment gene among the Brassicas. It also connects a classical mutant frequently used in genetics education with molecular markers and a known chromosomal location. PMID:17894874

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

    SciTech Connect

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

    1994-06-01

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

  6. Mapping of a new locus for congenital anomalies of the kidney and urinary tract on chromosome 8q24.

    PubMed

    Ashraf, Shazia; Hoskins, Bethan E; Chaib, Hassan; Hoefele, Julia; Pasch, Andreas; Saisawat, Pawaree; Trefz, Friedrich; Hacker, Hans W; Nuernberg, Gudrun; Nuernberg, Peter; Otto, Edgar A; Hildebrandt, Friedhelm

    2010-05-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) account for the majority of end-stage renal disease in children (50%). Previous studies have mapped autosomal dominant loci for CAKUT. We here report a genome-wide search for linkage in a large pedigree of Somalian descent containing eight affected individuals with a non-syndromic form of CAKUT. Clinical data and blood samples were obtained from a Somalian family with eight individuals with CAKUT including high-grade vesicoureteral reflux and unilateral renal agenesis. Total genome search for linkage was performed using a 50K SNP Affymetric DNA microarray. As neither parent is affected, the results of the SNP array were analysed under recessive models of inheritance, with and without the assumption of consanguinity. Using the non-consanguineous recessive model, a new gene locus (CAKUT1) for CAKUT was mapped to chromosome 8q24 with a significant maximum parametric Logarithm of the ODDs (LOD) score (LOD(max)) of 4.2. Recombinations were observed in two patients defining a critical genetic interval of 2.5 Mb physical distance flanked by markers SNP_A-1740062 and SNP_A-1653225. We have thus identified a new non-syndromic recessive gene locus for CAKUT (CAKUT1) on chromosome 8q24. The identification of the disease-causing gene will provide further insights into the pathogenesis of urinary tract malformations and mechanisms of renal development.

  7. Mapping the anthocyaninless (anl) locus in rapid-cycling Brassica rapa (RBr) to linkage group R9.

    PubMed

    Burdzinski, Carrie; Wendell, Douglas L

    2007-09-25

    Anthocyanins are flavonoid pigments that are responsible for purple coloration in the stems and leaves of a variety of plant species. Anthocyaninless (anl) mutants of Brassica rapa fail to produce anthocyanin pigments. In rapid-cycling Brassica rapa, also known as Wisconsin Fast Plants, the anthocyaninless trait, also called non-purple stem, is widely used as a model recessive trait for teaching genetics. Although anthocyanin genes have been mapped in other plants such as Arabidopsis thaliana, the anl locus has not been mapped in any Brassica species. We tested primer pairs known to amplify microsatellites in Brassicas and identified 37 that amplified a product in rapid-cycling Brassica rapa. We then developed three-generation pedigrees to assess linkage between the microsatellite markers and anl. 22 of the markers that we tested were polymorphic in our crosses. Based on 177 F2 offspring, we identified three markers linked to anl with LOD scores >or= 5.0, forming a linkage group spanning 46.9 cM. Because one of these markers has been assigned to a known B. rapa linkage group, we can now assign the anl locus to B. rapa linkage group R9. This study is the first to identify the chromosomal location of an anthocyanin pigment gene among the Brassicas. It also connects a classical mutant frequently used in genetics education with molecular markers and a known chromosomal location.

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

    SciTech Connect

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

    1997-02-01

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

  9. Selective genotyping with epistasis can be utilized for a major quantitative trait locus mapping in hypertension in rats.

    PubMed Central

    Ohno, Y; Tanase, H; Nabika, T; Otsuka, K; Sasaki, T; Suzawa, T; Morii, T; Yamori, Y; Saruta, T

    2000-01-01

    Epistasis used to be considered an obstacle in mapping quantitative trait loci (QTL) despite its significance. Numerous epistases have proved to be involved in quantitative genetics. We established a backcross model that demonstrates a major QTL for hypertension (Ht). Seventy-eight backcrossed rats (BC), derived from spontaneously hypertensive rats (SHR) and normotensive Fischer 344 rats, showed bimodal distribution of systolic blood pressure (BP) values and a phenotypic segregation ratio consistent with 1:1. In this backcross analysis, sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase (Serca) II heterozygotes showed widespread bimodality in frequency distribution of BP values and obviously demonstrated Ht. First, in genome-wide screening, Mapmaker/QTL analysis mapped Ht at a locus between D1Mgh8 and D1Mit4 near Sa in all 78 BC. The peak logarithm of the odds (LOD) score reached 5.3. Second, Serca II heterozygous and homozygous BC were analyzed separately using Mapmaker/QTL. In the 35 Serca II heterozygous BC, the peak LOD score was 3.8 at the same locus whereas it did not reach statistical significance in the 43 Serca II homozygotes. Third, to map Ht efficiently, we selected 18 Serca II heterozygous BC with 9 highest and 9 lowest BP values. In these 18 BC, the peak LOD score reached 8.1. In 17 of the 18, D1Mgh8 genotypes (homo or hetero) qualitatively cosegregated with BP phenotypes (high or low) (P < 0.0001, by chi-square analysis). In conclusion, selective genotyping with epistasis can be utilized for a major QTL mapping near Sa on chromosome 1 in SHR. PMID:10835399

  10. 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

    2016-05-13

    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.

  11. 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

  12. Mapping of the X-linked agammaglobulinemia locus by use of restriction fragment-length polymorphism.

    PubMed Central

    Kwan, S P; Kunkel, L; Bruns, G; Wedgwood, R J; Latt, S; Rosen, F S

    1986-01-01

    A molecular linkage analysis in 11 families with X-linked agammaglobulinemia (XLA) localized the XLA gene to the proximal part of the long arm of the human X chromosome. Significant linkage was detected between XLA and loci defined by two polymorphic DNA probes called 19-2 for the DXS3 locus and S21 for the DXS17 locus. Both localize to the region Xq21.3-Xq22. Most likely recombination distances (theta) and associated logarithm of the odds (lod) scores for the XLA-DXS3 and XLA-DXS17 pairs were theta = 0.04 morgans (lod, 3.65) and theta = 0 (lod, 2.17), respectively. Tight linkage between XLA and the locus DXS43 defined by the X short arm probe D2 (localized to Xp22-Xp21) was strongly excluded and we obtained no evidence for significant linkage between XLA and any other X short arm probe. The probe pair 19-2 and S21 should be informative for molecular linkage-based analysis of XLA segregation in the majority of families afflicted with this disorder. Images PMID:3003164

  13. Mapping of human microtubule-associated protein 1B in proximity to the spinal muscular atrophy locus at 5q13

    SciTech Connect

    Lien, L.L. Children's Hospital, Boston, MA ); Boyce, F.M.; Kunkel, L.M. ); Kleyn, P.; Brzustowicz, L.M.; Gilliam, T.C. New York State Psychiatric Inst., New York, NY ); Menninger, J.; Ward, D.C. )

    1991-09-01

    A polyclonal antiserum directed against the C-terminal domain of dystrophin was used to isolate a cDNA clone encoding an antigenically cross-reactive protein, microtubule-associated protein 1B (MAP-1B). Physical mapping of the human MAP-1B locus places its chromosomal location at 5q13, in proximity to the spinal muscular atrophy (SMA) locus. SMA is a degenerative disorder primarily affecting motor neurons. Genetic linkage analysis of SMA families using a human dinucleotide repeat polymorphism just 3{prime} of the MAP-1B gene has shown tight linkage to SMA mutations. These mapping data together with the postulated role of MAP-1B in neuronal morphogenesis and its localization in anterior horn motor neurons suggest a possible association with SMA.

  14. High-Density Genetic Linkage Map Construction and Quantitative Trait Locus Mapping for Hawthorn (Crataegus pinnatifida Bunge).

    PubMed

    Zhao, Yuhui; Su, Kai; Wang, Gang; Zhang, Liping; Zhang, Jijun; Li, Junpeng; Guo, Yinshan

    2017-07-14

    Genetic linkage maps are an important tool in genetic and genomic research. In this study, two hawthorn cultivars, Qiujinxing and Damianqiu, and 107 progenies from a cross between them were used for constructing a high-density genetic linkage map using the 2b-restriction site-associated DNA (2b-RAD) sequencing method, as well as for mapping quantitative trait loci (QTL) for flavonoid content. In total, 206,411,693 single-end reads were obtained, with an average sequencing depth of 57× in the parents and 23× in the progeny. After quality trimming, 117,896 high-quality 2b-RAD tags were retained, of which 42,279 were polymorphic; of these, 12,951 markers were used for constructing the genetic linkage map. The map contained 17 linkage groups and 3,894 markers, with a total map length of 1,551.97 cM and an average marker interval of 0.40 cM. QTL mapping identified 21 QTLs associated with flavonoid content in 10 linkage groups, which explained 16.30-59.00% of the variance. This is the first high-density linkage map for hawthorn, which will serve as a basis for fine-scale QTL mapping and marker-assisted selection of important traits in hawthorn germplasm and will facilitate chromosome assignment for hawthorn whole-genome assemblies in the future.

  15. Methionine synthase: high-resolution mapping of the human gene and evaluation as a candidate locus for neural tube defects.

    PubMed

    Brody, L C; Baker, P J; Chines, P S; Musick, A; Molloy, A M; Swanson, D A; Kirke, P N; Ghosh, S; Scott, J M; Mills, J L

    1999-08-01

    Periconceptual folate supplementation has been found to prevent the occurrence of many neural tube defects (NTDs). Consequently, genetic variation in folate metabolism genes is expected to contribute to the risk for neural tube defects. Methionine synthase catalyzes the vitamin B(12)-dependent conversion of homocysteine and 5-methyltetrahydrofolate to methionine and tetrahydrofolate. The observation that homocysteine and vitamin B(12) levels are independent predictors of NTD risk suggested that methionine synthase could be a candidate gene for NTDs. To assess the role of the MS gene in NTDs, we performed high-resolution physical mapping of the MS locus, isolated highly polymorphic markers linked to the MS gene, and tested for an association between specific MS alleles and NTDs. We mapped the MS gene to a position between 909 and 913 cR(10000) on chromosome 1 by radiation hybrid mapping. Polymorphic markers D1S1567 and D1S1568 map to locations no more than 900 and 194 kb from the MS gene, respectively. The segregation of these polymorphic markers was measured in 85 Irish NTD families. No allele of either marker showed a significant association with NTDs using the transmission disequilibrium test. A lack of association was also observed for the D1919G missense mutation within the gene. Our results suggest that inherited variation in the MS gene does not contribute to NTD risk in this population.

  16. Quantitative trait locus mapping reveals complex genetic architecture of quantitative virulence in the wheat pathogen Zymoseptoria tritici.

    PubMed

    Stewart, Ethan L; Croll, Daniel; Lendenmann, Mark H; Sanchez-Vallet, Andrea; Hartmann, Fanny E; Palma-Guerrero, Javier; Ma, Xin; McDonald, Bruce A

    2016-11-21

    We conducted a comprehensive analysis of virulence in the fungal wheat pathogen Zymoseptoria tritici using quantitative trait locus (QTL) mapping. High-throughput phenotyping based on automated image analysis allowed the measurement of pathogen virulence on a scale and with a precision that was not previously possible. Across two mapping populations encompassing more than 520 progeny, 540 710 pycnidia were counted and their sizes and grey values were measured. A significant correlation was found between pycnidia size and both spore size and number. Precise measurements of percentage leaf area covered by lesions provided a quantitative measure of host damage. Combining these large and accurate phenotypic datasets with a dense panel of restriction site-associated DNA sequencing (RADseq) genetic markers enabled us to genetically dissect pathogen virulence into components related to host damage and those related to pathogen reproduction. We showed that different components of virulence can be under separate genetic control. Large- and small-effect QTLs were identified for all traits, with some QTLs specific to mapping populations, cultivars and traits and other QTLs shared among traits within the same mapping population. We associated the presence of four accessory chromosomes with small, but significant, increases in several virulence traits, providing the first evidence for a meaningful function associated with accessory chromosomes in this organism. A large-effect QTL involved in host specialization was identified on chromosome 7, leading to the identification of candidate genes having a large effect on virulence.

  17. Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas.

    PubMed

    Fejerman, Laura; Chen, Gary K; Eng, Celeste; Huntsman, Scott; Hu, Donglei; Williams, Amy; Pasaniuc, Bogdan; John, Esther M; Via, Marc; Gignoux, Christopher; Ingles, Sue; Monroe, Kristine R; Kolonel, Laurence N; Torres-Mejía, Gabriela; Pérez-Stable, Eliseo J; Burchard, Esteban González; Henderson, Brian E; Haiman, Christopher A; Ziv, Elad

    2012-04-15

    Among US Latinas and Mexican women, those with higher European ancestry have increased risk of breast cancer. We combined an admixture mapping and genome-wide association mapping approach to search for genomic regions that may explain this observation. Latina women with breast cancer (n= 1497) and Latina controls (n= 1272) were genotyped using Affymetrix and Illumina arrays. We inferred locus-specific genetic ancestry and compared the ancestry between cases and controls. We also performed single nucleotide polymorphism (SNP) association analyses in regions of interest. Correction for multiple-hypothesis testing was conducted using permutations (P(corrected)). We identified one region where genetic ancestry was significantly associated with breast cancer risk: 6q25 [odds ratio (OR) per Indigenous American chromosome 0.75, 95% confidence interval (CI): 0.65-0.85, P= 1.1 × 10(-5), P(corrected)= 0.02]. A second region on 11p15 showed a trend towards association (OR per Indigenous American chromosome 0.77, 95% CI: 0.68-0.87, P= 4.3 × 10(-5), P(corrected)= 0.08). In both regions, breast cancer risk decreased with higher Indigenous American ancestry in concordance with observations made on global ancestry. The peak of the 6q25 signal includes the estrogen receptor 1 (ESR1) gene and 5' region, a locus previously implicated in breast cancer. Genome-wide association analysis found that a multi-SNP model explained the admixture signal in both regions. Our results confirm that the association between genetic ancestry and breast cancer risk in US Latinas is partly due to genetic differences between populations of European and Indigenous Americans origin. Fine-mapping within the 6q25 and possibly the 11p15 loci will lead to the discovery of the biologically functional variant/s behind this association.

  18. Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas

    PubMed Central

    Fejerman, Laura; Chen, Gary K.; Eng, Celeste; Huntsman, Scott; Hu, Donglei; Williams, Amy; Pasaniuc, Bogdan; John, Esther M.; Via, Marc; Gignoux, Christopher; Ingles, Sue; Monroe, Kristine R.; Kolonel, Laurence N.; Torres-Mejía, Gabriela; Pérez-Stable, Eliseo J.; González Burchard, Esteban; Henderson, Brian E.; Haiman, Christopher A.; Ziv, Elad

    2012-01-01

    Among US Latinas and Mexican women, those with higher European ancestry have increased risk of breast cancer. We combined an admixture mapping and genome-wide association mapping approach to search for genomic regions that may explain this observation. Latina women with breast cancer (n= 1497) and Latina controls (n= 1272) were genotyped using Affymetrix and Illumina arrays. We inferred locus-specific genetic ancestry and compared the ancestry between cases and controls. We also performed single nucleotide polymorphism (SNP) association analyses in regions of interest. Correction for multiple-hypothesis testing was conducted using permutations (Pcorrected). We identified one region where genetic ancestry was significantly associated with breast cancer risk: 6q25 [odds ratio (OR) per Indigenous American chromosome 0.75, 95% confidence interval (CI): 0.65–0.85, P= 1.1 × 10−5, Pcorrected= 0.02]. A second region on 11p15 showed a trend towards association (OR per Indigenous American chromosome 0.77, 95% CI: 0.68–0.87, P= 4.3 × 10−5, Pcorrected= 0.08). In both regions, breast cancer risk decreased with higher Indigenous American ancestry in concordance with observations made on global ancestry. The peak of the 6q25 signal includes the estrogen receptor 1 (ESR1) gene and 5′ region, a locus previously implicated in breast cancer. Genome-wide association analysis found that a multi-SNP model explained the admixture signal in both regions. Our results confirm that the association between genetic ancestry and breast cancer risk in US Latinas is partly due to genetic differences between populations of European and Indigenous Americans origin. Fine-mapping within the 6q25 and possibly the 11p15 loci will lead to the discovery of the biologically functional variant/s behind this association. PMID:22228098

  19. Construction of a High-Density Genetic Map and Quantitative Trait Locus Mapping in the Sea Cucumber Apostichopus japonicus

    PubMed Central

    Tian, Meilin; Li, Yangping; Jing, Jing; Mu, Chuang; Du, Huixia; Dou, Jinzhuang; Mao, Junxia; Li, Xue; Jiao, Wenqian; Wang, Yangfan; Hu, Xiaoli; Wang, Shi; Wang, Ruijia; Bao, Zhenmin

    2015-01-01

    Genetic linkage maps are critical and indispensable tools in a wide range of genetic and genomic research. With the advancement of genotyping-by-sequencing (GBS) methods, the construction of a high-density and high-resolution linkage maps has become achievable in marine organisms lacking sufficient genomic resources, such as echinoderms. In this study, high-density, high-resolution genetic map was constructed for a sea cucumber species, Apostichopus japonicus, utilizing the 2b-restriction site-associated DNA (2b-RAD) method. A total of 7839 markers were anchored to the linkage map with the map coverage of 99.57%, to our knowledge, this is the highest marker density among echinoderm species. QTL mapping and association analysis consistently captured one growth-related QTL located in a 5 cM region of linkage group (LG) 5. An annotated candidate gene, retinoblastoma-binding protein 5 (RbBP5), which has been reported to be an important regulator of cell proliferation, was recognized in the QTL region. This linkage map represents a powerful tool for research involving both fine-scale QTL mapping and marker assisted selection (MAS), and will facilitate chromosome assignment and improve the whole-genome assembly of sea cucumber in the future. PMID:26439740

  20. Evidence that a locus for familial psoriasis maps to chromosome 4q.

    PubMed

    Matthews, D; Fry, L; Powles, A; Weber, J; McCarthy, M; Fisher, E; Davies, K; Williamson, R

    1996-10-01

    Psoriasis is an inflammatory skin disease that affects 2% of the population. It is characterised by red, scaly skin patches which are usually found on the scalp, elbows and knees, and may be associated with severe arthropathy. The lesions are caused by abnormal keratinocyte proliferation, and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age. Psoriasis is recognised to have a large genetic component. Twin studies show the concordance in monozygotic twins to be between 65-70%, compared to between 15-20% in dizygotic twins. Family studies estimate the risk to first degree relatives at between 8-23%. However, there are also several environmental factors, including streptococcal infection and stress, that affect the onset and presentation of the disease. The mode of inheritance of psoriasis is unclear. We conducted a genome-wide scan to search for psoriasis susceptibility loci in a single large multiplex family. Parametric linkage analysis indicated that a susceptibility locus for familial psoriasis was located on chromosome 4q. Investigation of this locus in five further multiplex families using both parametric and non-parametric methods gave significant localisation to chromosome 4q. The maximum total pairwise lod score obtained was 3.03 with the microsatellite marker D4S1535 at theta = 0.08. Non-parametric multipoint analysis with GENEHUNTER- demonstrated significant excess allele sharing, with a P value of 0.0026, at the same locus.

  1. 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.

  2. Composite Interval Mapping Based on Lattice Design for Error Control May Increase Power of Quantitative Trait Locus Detection

    PubMed Central

    Huang, Zhongwen; Zhao, Tuanjie; Xing, Guangnan; Gai, Junyi; Guan, Rongzhan

    2015-01-01

    Experimental error control is very important in quantitative trait locus (QTL) mapping. Although numerous statistical methods have been developed for QTL mapping, a QTL detection model based on an appropriate experimental design that emphasizes error control has not been developed. Lattice design is very suitable for experiments with large sample sizes, which is usually required for accurate mapping of quantitative traits. However, the lack of a QTL mapping method based on lattice design dictates that the arithmetic mean or adjusted mean of each line of observations in the lattice design had to be used as a response variable, resulting in low QTL detection power. As an improvement, we developed a QTL mapping method termed composite interval mapping based on lattice design (CIMLD). In the lattice design, experimental errors are decomposed into random errors and block-within-replication errors. Four levels of block-within-replication errors were simulated to show the power of QTL detection under different error controls. The simulation results showed that the arithmetic mean method, which is equivalent to a method under random complete block design (RCBD), was very sensitive to the size of the block variance and with the increase of block variance, the power of QTL detection decreased from 51.3% to 9.4%. In contrast to the RCBD method, the power of CIMLD and the adjusted mean method did not change for different block variances. The CIMLD method showed 1.2- to 7.6-fold higher power of QTL detection than the arithmetic or adjusted mean methods. Our proposed method was applied to real soybean (Glycine max) data as an example and 10 QTLs for biomass were identified that explained 65.87% of the phenotypic variation, while only three and two QTLs were identified by arithmetic and adjusted mean methods, respectively. PMID:26076140

  3. Mapping and molecular cloning of the phn (psiD) locus for phosphonate utilization in Escherichia coli.

    PubMed Central

    Wanner, B L; Boline, J A

    1990-01-01

    The Escherichia coli phn (psiD) locus encodes genes for phosphonate (Pn) utilization, for phn (psiD) mutations abolish the ability to use as a sole P source a Pn with a substituted C-2 or unsubstituted hydrocarbon group such as 2-aminoethylphosphonate (AEPn) or methylphosphonate (MPn), respectively. Even though the E. coli K-12 phosphate starvation-inducible (psi) phn (psiD) gene(s) shows normal phosphate (Pi) control, Pn utilization is cryptic in E. coli K-12, as well as in several members of the E. coli reference (ECOR) collection which are closely related to K-12. For these bacteria, an activating mutation near the phn (psiD) gene is necessary for growth on a Pn as the sole P source. Most E. coli strains, including E. coli B, are naturally Phn+; a few E. coli strains are Phn- and are deleted for phn DNA sequences. The Phn+ phn(EcoB) DNA was molecularly cloned by using the mini-Mu in vivo cloning procedure and complementation of an E. coli K-12 delta phn mutant. The phn(EcoB) DNA hybridized to overlapping lambda clones in the E. coli K-12 gene library (Y. Kohara, K. Akiyama, and K. Isono, Cell 50:495-508, 1987) which contain the 93-min region, thus showing that the phn (psiD) locus was itself cloned and verifying our genetic data on its map location. The cryptic phn(EcoK) DNA has an additional 100 base pairs that is absent in the naturally Phn+ phn(EcoB) sequence. However, no gross structural change was detected in independent Phn+ phn(EcoK) mutants that have activating mutations near the phn locus. Images FIG. 2 PMID:2155195

  4. Mapping and molecular cloning of the phn (psiD) locus for phosphonate utilization in Escherichia coli.

    PubMed

    Wanner, B L; Boline, J A

    1990-03-01

    The Escherichia coli phn (psiD) locus encodes genes for phosphonate (Pn) utilization, for phn (psiD) mutations abolish the ability to use as a sole P source a Pn with a substituted C-2 or unsubstituted hydrocarbon group such as 2-aminoethylphosphonate (AEPn) or methylphosphonate (MPn), respectively. Even though the E. coli K-12 phosphate starvation-inducible (psi) phn (psiD) gene(s) shows normal phosphate (Pi) control, Pn utilization is cryptic in E. coli K-12, as well as in several members of the E. coli reference (ECOR) collection which are closely related to K-12. For these bacteria, an activating mutation near the phn (psiD) gene is necessary for growth on a Pn as the sole P source. Most E. coli strains, including E. coli B, are naturally Phn+; a few E. coli strains are Phn- and are deleted for phn DNA sequences. The Phn+ phn(EcoB) DNA was molecularly cloned by using the mini-Mu in vivo cloning procedure and complementation of an E. coli K-12 delta phn mutant. The phn(EcoB) DNA hybridized to overlapping lambda clones in the E. coli K-12 gene library (Y. Kohara, K. Akiyama, and K. Isono, Cell 50:495-508, 1987) which contain the 93-min region, thus showing that the phn (psiD) locus was itself cloned and verifying our genetic data on its map location. The cryptic phn(EcoK) DNA has an additional 100 base pairs that is absent in the naturally Phn+ phn(EcoB) sequence. However, no gross structural change was detected in independent Phn+ phn(EcoK) mutants that have activating mutations near the phn locus.

  5. Association Mapping Provides Insights into the Origin and the Fine Structure of the Sorghum Aluminum Tolerance Locus, AltSB

    PubMed Central

    Caniato, Fernanda F.; Hamblin, Martha T.; Guimaraes, Claudia T.; Zhang, Zhiwu; Schaffert, Robert E.; Kochian, Leon V.; Magalhaes, Jurandir V.

    2014-01-01

    Root damage caused by aluminum (Al) toxicity is a major cause of grain yield reduction on acid soils, which are prevalent in tropical and subtropical regions of the world where food security is most tenuous. In sorghum, Al tolerance is conferred by SbMATE, an Al-activated root citrate efflux transporter that underlies the major Al tolerance locus, AltSB, on sorghum chromosome 3. We used association mapping to gain insights into the origin and evolution of Al tolerance in sorghum and to detect functional variants amenable to allele mining applications. Linkage disequilibrium across the AltSB locus decreased much faster than in previous reports in sorghum, and reached basal levels at approximately 1000 bp. Accordingly, intra-locus recombination events were found to be extensive. SNPs and indels highly associated with Al tolerance showed a narrow frequency range, between 0.06 and 0.1, suggesting a rather recent origin of Al tolerance mutations within AltSB. A haplotype network analysis suggested a single geographic and racial origin of causative mutations in primordial guinea domesticates in West Africa. Al tolerance assessment in accessions harboring recombinant haplotypes suggests that causative polymorphisms are localized to a ∼6 kb region including intronic polymorphisms and a transposon (MITE) insertion, whose size variation has been shown to be positively correlated with Al tolerance. The SNP with the strongest association signal, located in the second SbMATE intron, recovers 9 of the 14 highly Al tolerant accessions and 80% of all the Al tolerant and intermediately tolerant accessions in the association panel. Our results also demonstrate the pivotal importance of knowledge on the origin and evolution of Al tolerance mutations in molecular breeding applications. Allele mining strategies based on associated loci are expected to lead to the efficient identification, in diverse sorghum germplasm, of Al tolerant accessions able maintain grain yields under Al

  6. Association mapping provides insights into the origin and the fine structure of the sorghum aluminum tolerance locus, AltSB.

    PubMed

    Caniato, Fernanda F; Hamblin, Martha T; Guimaraes, Claudia T; Zhang, Zhiwu; Schaffert, Robert E; Kochian, Leon V; Magalhaes, Jurandir V

    2014-01-01

    Root damage caused by aluminum (Al) toxicity is a major cause of grain yield reduction on acid soils, which are prevalent in tropical and subtropical regions of the world where food security is most tenuous. In sorghum, Al tolerance is conferred by SbMATE, an Al-activated root citrate efflux transporter that underlies the major Al tolerance locus, AltSB, on sorghum chromosome 3. We used association mapping to gain insights into the origin and evolution of Al tolerance in sorghum and to detect functional variants amenable to allele mining applications. Linkage disequilibrium across the AltSB locus decreased much faster than in previous reports in sorghum, and reached basal levels at approximately 1000 bp. Accordingly, intra-locus recombination events were found to be extensive. SNPs and indels highly associated with Al tolerance showed a narrow frequency range, between 0.06 and 0.1, suggesting a rather recent origin of Al tolerance mutations within AltSB. A haplotype network analysis suggested a single geographic and racial origin of causative mutations in primordial guinea domesticates in West Africa. Al tolerance assessment in accessions harboring recombinant haplotypes suggests that causative polymorphisms are localized to a ∼6 kb region including intronic polymorphisms and a transposon (MITE) insertion, whose size variation has been shown to be positively correlated with Al tolerance. The SNP with the strongest association signal, located in the second SbMATE intron, recovers 9 of the 14 highly Al tolerant accessions and 80% of all the Al tolerant and intermediately tolerant accessions in the association panel. Our results also demonstrate the pivotal importance of knowledge on the origin and evolution of Al tolerance mutations in molecular breeding applications. Allele mining strategies based on associated loci are expected to lead to the efficient identification, in diverse sorghum germplasm, of Al tolerant accessions able maintain grain yields under Al

  7. Refined Mapping of the Renal Failure Rf-3 Quantitative Trait Locus

    PubMed Central

    O'Meara, Caitlin C.; Lazar, Jozef; Hoffman, Matthew; Moreno, Carol

    2011-01-01

    Rf-3, a quantitative trait locus (QTL) on rat chromosome 3, affects the development of CKD in Fawn-Hooded Hypertensive (FHH) rats. This QTL spans 110 Mb and approximately 1400 genes; therefore, narrowing the position of this locus is necessary to elucidate potential candidate genes. Here, we used congenic models and comparative genomics to refine the Rf-3 candidate region. We generated congenic lines carrying smaller intervals (subcongenics) of the Rf-3 region and used these lines to reduce the Rf-3 candidate region by 94% (to 7.1 Mb). We used comparative genomics to identify QTL for both nephropathy and albuminuria in the syntenic region of this interval for both human and mouse. We also used the overlapping homologous regions to reduce the number of likely positional candidate genes to 13 known or predicted genes. By combining congenic models and cross-species studies, we narrowed the list of candidate genes to a level that we could sequence the whole interval to further identify the causative gene in future studies. PMID:21127141

  8. Charactering the ZFAND3 gene mapped in the sex-determining locus in hybrid tilapia (Oreochromis spp.)

    PubMed Central

    Ma, Keyi; Liao, Minghui; Liu, Feng; Ye, Baoqing; Sun, Fei; Yue, Gen Hua

    2016-01-01

    Zinc finger AN1-type domain 3 (ZFAND3) is essential for spermatogenesis in mice. However, its function in teleosts remains unclear. In this study, we characterized the ZFAND3 gene (termed as OsZFAND3) in an important food fish, tilapia. The OsZFAND3 cDNA sequence is 1,050 bp in length, containing an ORF of 615 bp, which encodes a putative peptide of 204 amino acid residues. Quantitative real-time PCR revealed that the OsZFAND3 transcripts were exclusively expressed in the testis and ovary. In situ hybridization showed that the high expression of OsZFAND3 transcripts was predominantly localized in the spermatocyte and spermatid. These results suggest that OsZFAND3 is involved in male germ cell maturation. Three single nucleotide polymorphisms (SNPs) were detected in the introns of OsZFAND3. The OsZFAND3 gene was mapped in the sex-determining locus on linkage group 1 (LG1). The three SNPs in the OsZFAND3 gene were strictly associated with sex phenotype, suggesting that the OsZFAND3 gene is tightly linked to the sex-determining locus. Our study provides new insights into the functions of the OsZFAND3 gene in tilapia and a foundation for further detailed analysis of the OsZFAND3 gene in sex determination and differentiation. PMID:27137111

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

    SciTech Connect

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

    1995-01-20

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

  10. Localization of causal locus in the genome of the brown macroalga Ectocarpus: NGS-based mapping and positional cloning approaches.

    PubMed

    Billoud, Bernard; Jouanno, Émilie; Nehr, Zofia; Carton, Baptiste; Rolland, Élodie; Chenivesse, Sabine; Charrier, Bénédicte

    2015-01-01

    Mutagenesis is the only process by which unpredicted biological gene function can be identified. Despite that several macroalgal developmental mutants have been generated, their causal mutation was never identified, because experimental conditions were not gathered at that time. Today, progresses in macroalgal genomics and judicious choices of suitable genetic models make mutated gene identification possible. This article presents a comparative study of two methods aiming at identifying a genetic locus in the brown alga Ectocarpus siliculosus: positional cloning and Next-Generation Sequencing (NGS)-based mapping. Once necessary preliminary experimental tools were gathered, we tested both analyses on an Ectocarpus morphogenetic mutant. We show how a narrower localization results from the combination of the two methods. Advantages and drawbacks of these two approaches as well as potential transfer to other macroalgae are discussed.

  11. Localization of causal locus in the genome of the brown macroalga Ectocarpus: NGS-based mapping and positional cloning approaches

    PubMed Central

    Billoud, Bernard; Jouanno, Émilie; Nehr, Zofia; Carton, Baptiste; Rolland, Élodie; Chenivesse, Sabine; Charrier, Bénédicte

    2015-01-01

    Mutagenesis is the only process by which unpredicted biological gene function can be identified. Despite that several macroalgal developmental mutants have been generated, their causal mutation was never identified, because experimental conditions were not gathered at that time. Today, progresses in macroalgal genomics and judicious choices of suitable genetic models make mutated gene identification possible. This article presents a comparative study of two methods aiming at identifying a genetic locus in the brown alga Ectocarpus siliculosus: positional cloning and Next-Generation Sequencing (NGS)-based mapping. Once necessary preliminary experimental tools were gathered, we tested both analyses on an Ectocarpus morphogenetic mutant. We show how a narrower localization results from the combination of the two methods. Advantages and drawbacks of these two approaches as well as potential transfer to other macroalgae are discussed. PMID:25745426

  12. Genetic map of randomly amplified DNA polymorphisms closely linked to the mating type locus of tetrahymenta thermophila

    SciTech Connect

    Lynch, T.J.; Brickner, J.; Orias, E.; Nakano, K.J.

    1995-12-01

    We have used the PCR-based randomly amplified polymorphic DNA (RAPD) method to efficiently identify and map DNA polymorphisms in the ciliated protozoan Tetrahymena thermophila. The polymorphisms segregate as Mendelian genetic markers. A targeted screen, using DNA from pooled meiotic segregants, yielded the polymorphisms most closely linked to the mat locus. A total of 10 polymorphisms linked to the mat-Pmr segment of the left arm of micronuclear chromosome 2 have been identified. This constitutes the largest linkage group described in T. thermophila. We also provide here the first crude estimate of the frequency of meiotic recombination in the mat region, 20 kb/cM. This frequency is much higher than that observed in most other eukaryotes. Special features of Tetrahymena genetics enhanced the power of the RAPD method: the ability to obtain in a single step meiotic segregants that are whole-genome homozygotes and the availability of nullisomic strains permitting quick deletion mapping of polymorphisms to micronuclear chromosomes or chromosomes segments. The RAPD method appears to provide a practical and relatively inexpensive approach to the construction of a high-resolution map of the Tetrahymena genome. 39 refs., 5 figs., 4 tabs.

  13. Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk

    PubMed Central

    Guo, Xingyi; Long, Jirong; Zeng, Chenjie; Michailidou, Kyriaki; Ghoussaini, Maya; Bolla, Manjeet K.; Wang, Qin; Milne, Roger L.; Shu, Xiao-Ou; Cai, Qiuyin; Beesley, Jonathan; Kar, Siddhartha P.; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Blot, William; Bogdanova, Natalia; Bojesen, Stig E.; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Cai, Hui; Canisius, Sander; Chang-Claude, Jenny; Choi, Ji-Yeob; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Droit, Arnaud; Dörk, Thilo; Fasching, Peter A.; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gaborieau, Valerie; García-Closas, Montserrat; Giles, Graham G.; Grip, Mervi; Guénel, Pascal; Haiman, Christopher A.; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L.; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Khan, Sofia; Knight, Julia A.; Kosma, Veli-Matti; Lambrechts, Diether; Marchand, Loic Le; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; McLean, Catriona A.; Meindl, Alfons; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Olson, Janet E.; Orr, Nick; Peterlongo, Paolo; Putti, Thomas Choudary; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Shen, Chen-Yang; Shi, Jiajun; Shrubsole, Martha J; Southey, Melissa C.; Swerdlow, Anthony; Teo, Soo Hwang; Thienpont, Bernard; Toland, Amanda Ewart; Tollenaar, Robert A.E.M.; Tomlinson, Ian P.M.; Truong, Thérèse; Tseng, Chiu-chen; van den Ouweland, Ans; Wen, Wanqing; Winqvist, Robert; Wu, Anna; Yip, Cheng Har; Zamora, M. Pilar; Zheng, Ying; Hall, Per; Pharoah, Paul D.P.; Simard, Jacques; Chenevix-Trench, Georgia; Dunning, Alison M.; Easton, Douglas F.; Zheng, Wei

    2015-01-01

    Background A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 (conditional p = 2.51 × 10−4; OR = 1.04; 95% CI 1.02–1.07) and rs77928427 (p = 1.86 × 10−4; OR = 1.04; 95% CI 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk. PMID:26354892

  14. Familial vestibulocerebellar disorder maps to chromosome 13q31-q33: a new nystagmus locus

    PubMed Central

    Ragge, N; Hartley, C; Dearlove, A; Walker, J; Russell-Eggitt, I; Harris, C

    2003-01-01

    Design: Observational and experimental study. Methods: We carried out a phenotypic study of a unique four generation family with nystagmus. We performed genetic linkage studies including a genome wide search. Results: Affected family members developed vestibulocerebellar type nystagmus in the first two years of life. A higher incidence of strabismus was noted in affected members. Haplotype construction and analysis of recombination events linked the disorder to a locus (NYS4) on chromosome 13q31-q33 with a lod score of 6.322 at θ=0 for D13S159 and narrowed the region to a 13.8 cM region between markers D13S1300 and D13S158. Conclusions: This study suggests that the early onset acquired nystagmus seen in this family is caused by a single gene defect. Identification of the gene may hold the key to understanding pathways for early eye stabilisation and strabismus. PMID:12525540

  15. The mapping of DFNB62, a new locus for autosomal recessive non-syndromic hearing impairment, to chromosome 12p13.2-p11.23.

    PubMed

    Ali, G; Santos, R L P; John, P; Wambangco, M A L; Lee, K; Ahmad, W; Leal, Sm

    2006-05-01

    Autosomal recessive non-syndromic hearing impairment (ARNSHI) is the most common form of prelingual inherited hearing impairment (HI). Here is described the mapping of a novel ARNSHI locus in a consanguineous Pakistani family with profound congenital HI. Two-point and multipoint linkage analyses were performed for the genome scan and fine mapping markers. Haplotypes were constructed to determine the region of homozygosity. At theta = 0, the maximum two-point LOD score of 4.0 was obtained at marker AAC040. A maximum multipoint LOD score of 5.3 was derived at marker D12S320, with the three-unit support interval demarcated by D12S89 and D12S1042. The region of homozygosity is flanked by markers D12S358 and D12S1042, which corresponds to 22.4 cM according to the Rutgers combined linkage-physical map of the human genome and spans 15.0 Mb on the sequence-based physical map. A novel ARNSHI locus DFNB62 was mapped to chromosome 12p13.2-p11.23. DFNB62 represents the second ARNSHI locus to map to chromosome 12.

  16. Admixture Mapping Identifies a Quantitative Trait Locus Associated with FEV1/FVC in the COPDGene Study

    PubMed Central

    Parker, Margaret M.; Foreman, Marilyn G.; Abel, Haley J.; Mathias, Rasika A.; Hetmanksi, Jacqueline B.; Crapo, James D.; Silverman, Edwin K.; Beaty, Terri H.

    2014-01-01

    African Americans are admixed with genetic contributions from European and African ancestral populations. Admixture mapping leverages this information to map genes influencing differential disease risk across populations. We performed admixture and association mapping in 3300 African American current or former smokers from the COPDGene Study. We analyzed estimated local ancestry and SNP genotype information to identify regions associated with FEV1/FVC, the ratio of forced expiratory volume in one second to forced vital capacity, measured by spirometry performed after bronchodilator administration. Global African ancestry inversely associated with FEV1/FVC (p = 0.035). Genome-wide admixture analysis, controlling for age, gender, body mass index, current smoking status, pack-years smoked, and four principal components summarizing the genetic background of African Americans in the COPDGene Study, identified a region on chromosome 12q14.1 associated with FEV1/FVC (p = 2.1 × 10-6) when regressed on local ancestry. Allelic association in this region of chromosome 12 identified an intronic variant in FAM19A2 (rs348644) as associated with FEV1/FVC (p=1.76 × 10-6). By combining admixture and association mapping, a marker on chromosome 12q14.1 was identified as being associated with reduced FEV1/FVC ratio among African-Americans in the COPDGene Study. PMID:25112515

  17. Mapping Multiple Sclerosis Susceptibility to the HLA-DR Locus in African Americans

    PubMed Central

    Oksenberg, Jorge R.; Barcellos, Lisa F.; Cree, Bruce A. C.; Baranzini, Sergio E.; Bugawan, Teodorica L.; Khan, Omar; Lincoln, Robin R.; Swerdlin, Amy; Mignot, Emmanuel; Lin, Ling; Goodin, Douglas; Erlich, Henry A.; Schmidt, Silke; Thomson, Glenys; Reich, David E.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Hauser, Stephen L.

    2004-01-01

    An underlying complex genetic susceptibility exists in multiple sclerosis (MS), and an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been repeatedly demonstrated in high-risk (northern European) populations. It is unknown whether the effect is explained by the HLA-DRB1 or the HLA-DQB1 gene within the susceptibility haplotype, which are in strong linkage disequilibrium (LD). African populations are characterized by greater haplotypic diversity and distinct patterns of LD compared with northern Europeans. To better localize the HLA gene responsible for MS susceptibility, case-control and family-based association studies were performed for DRB1 and DQB1 loci in a large and well-characterized African American data set. A selective association with HLA-DRB1*15 was revealed, indicating a primary role for the DRB1 locus in MS independent of DQB1*0602. This finding is unlikely to be solely explained by admixture, since a substantial proportion of the susceptibility chromosomes from African American patients with MS displayed haplotypes consistent with an African origin. PMID:14669136

  18. 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.

  19. Mapping of a further malignant hyperthermia susceptibility locus to chromosome 3q13.1

    SciTech Connect

    Sudbrak, R.; Deufel, T.; Procaccio, V.; Lunardi, J.; Klausnitzer, M.; Mueller, C.R.; Hartung, E.J.; Curran, J.L.; Stewart, A.D.

    1995-03-01

    Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disease for which MH susceptibility (MHS) is transmitted as an autosomal dominant trait. A potentially life-threatening MH crisis is triggered by exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. The first malignant hyperthermia susceptibility locus (MHS1) was identified on human chromosome 19{sub q}13.1, and evidence has been obtained that defects in the gene for the calcium-release channel of skeletal muscle sarcoplasmic reticulum (ryanodine receptor; RYR1) can cause some forms of MH. However, MH has been shown to be genetically heterogeneous, and additional loci on chromosomes 17q and 7q have been suggested. In a collaborative search of the human genome with polymorphic microsatellite markers, we now found linkage of the MHS phenotype, as assessed by the European in vitro contracture test protocol, to markers defining a 1-cM interval on chromosome 3q13.1. A maximum multipoint lod score of 3.22 was obtained in a single German pedigree with classical MH, and none of the other pedigrees investigated in this study showed linkage to this region. Linkage to both MHS1/RYR1 and putative loci on chromosome 17q and 7q were excluded. This study supports the view that considerable genetic heterogeneity exists in MH. 47 refs., 2 figs., 3 tabs.

  20. Fine mapping of the McLeod locus (XK) to a 150-380-kb region in Xp21

    SciTech Connect

    Ho, M.F.; Monaco, A.P. ); Blonden, L.A.J.; Ommen, G.J.B. van ); Affara, N.A.; Ferguson-Smith, M.A. ); Lehrach, H. )

    1992-02-01

    McLeod syndrome characterized by acanthocytosis and the absence of a red-blood-cell Kell antigen (Kx), is a multisystem disorder involving a late-onset myopathy, splenomegaly, and neurological defects. The locus for this syndrome has been mapped, by deletion analysis, to a region between the loci for Duchenne muscular dystrophy (DMD) and chronic granulomatous disease (CGD). In this study, the authors describe a new marker, 3BH/R 0.3 (DXS 709), isolated by cloning the deletion breakpoint of a DMD patient. A long-range restriction map of Xp21, encompassing the gene loci for McLeod and CGD, was constructed, and multiple CpG islands were found clustered in a 700-kb region. Using the new marker, they have limited the McLeod syndrome critical region to 150-380-kb. Within this interval, two CpG-rich islands which may represent candidate sites for the McLeod gene were identified.

  1. Fine mapping of the sunflower resistance locus Pl(ARG) introduced from the wild species Helianthus argophyllus.

    PubMed

    Wieckhorst, S; Bachlava, E; Dussle, C M; Tang, S; Gao, W; Saski, C; Knapp, S J; Schön, C-C; Hahn, V; Bauer, E

    2010-11-01

    Downy mildew, caused by Plasmopara halstedii, is one of the most destructive diseases in cultivated sunflower (Helianthus annuus L.). The dominant resistance locus Pl(ARG) originates from silverleaf sunflower (H. argophyllus Torrey and Gray) and confers resistance to all known races of P. halstedii. We mapped Pl(ARG) on linkage group (LG) 1 of (cms)HA342 × ARG1575-2, a population consisting of 2,145 F(2) individuals. Further, we identified resistance gene candidates (RGCs) that cosegregated with Pl(ARG) as well as closely linked flanking markers. Markers from the target region were mapped with higher resolution in NDBLOS(sel) × KWS04, a population consisting of 2,780 F(2) individuals that does not segregate for Pl(ARG). A large-insert sunflower bacterial artificial chromosome (BAC) library was screened with overgo probes designed for markers RGC52 and RGC151, which cosegregated with Pl(ARG). Two RGC-containing BAC contigs were anchored to the Pl(ARG) region on LG 1.

  2. The bottle gourd genome provides insights into Cucurbitaceae evolution and facilitates mapping of a Papaya ringspot virus resistance locus.

    PubMed

    Wu, Shan; Shamimuzzaman, Md; Sun, Honghe; Salse, Jerome; Sui, Xuelian; Wilder, Alan; Wu, Zujian; Levi, Amnon; Xu, Yong; Ling, Kai-Shu; Fei, Zhangjun

    2017-09-23

    Bottle gourd (Lagenaria siceraria) is an important vegetable crop as well as a rootstock for other cucurbit crops. In this study, we report a high-quality 313.4-Mb genome sequence of a bottle gourd inbred line, USVL1VR-Ls, with a scaffold N50 of 8.7 Mb and the longest of 19.0 Mb. About 98.3% of the assembled scaffolds are anchored to the 11 pseudomolecules. Our comparative genomic analysis identifies chromosome-level syntenic relationships between bottle gourd and other cucurbits, as well as lineage-specific gene family expansions in bottle gourd. We reconstruct the genome of the most recent common ancestor of Cucurbitaceae, which reveals that the ancestral Cucurbitaceae karyotypes consists of 12 protochromosomes with 18,534 protogenes. The 12 protochromosomes are largely retained in the modern melon genome, while have undergone different degrees of shuffling events in other investigated cucurbit genomes. The eleven bottle gourd chromosomes derive from the ancestral Cucurbitaceae karyotypes followed by 19 chromosomal fissions and 20 fusions. The bottle gourd genome sequence has facilitated the mapping of a dominant monogenic locus, Prs, conferring Papaya ringspot virus (PRSV) resistance in bottle gourd, to a 317.8-kb region on chromosome 1. We have developed a cleaved amplified polymorphic sequence (CAPS) marker tightly linked to the Prs locus and demonstrated its potential application in marker-assisted selection of PRSV resistance in bottle gourd. This study provides insights into the paleohistory of Cucurbitaceae genome evolution, and the high-quality genome sequence of bottle gourd provides a useful resource for plant comparative genomics studies and cucurbit improvement. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Quantitative trait locus gene mapping: a new method for locating alcohol response genes.

    PubMed

    Crabbe, J C

    1996-01-01

    Alcoholism is a multigenic trait with important non-genetic determinants. Studies with genetic animal models of susceptibility to several of alcohol's effects suggest that several genes contributing modest effects on susceptibility (Quantitative Trait Loci, or QTLs) are important. A new technique of QTL gene mapping has allowed the identification of the location in mouse genome of several such QTLs. The method is described, and the locations of QTLs affecting the acute alcohol withdrawal reaction are described as an example of the method. Verification of these QTLs in ancillary studies is described and the strengths, limitations, and future directions to be pursued are discussed. QTL mapping is a promising method for identifying genes in rodents with the hope of directly extrapolating the results to the human genome. This review is based on a paper presented at the First International Congress of the Latin American Society for Biomedical Research on Alcoholism, Santiago, Chile, November 1994.

  4. A high-resolution genetic map of mouse chromosome 5 encompassing the reeler (rl) locus

    SciTech Connect

    Beckers, M.C.; Bar, I.; Huynh-Thu, T.

    1994-10-01

    Using interspecific crosses between BALB/c and Mus spretus (SEG) mice, the murine reeler (rl) gene was mapped to the proximal region of chromosome 5 between the hepatocyte growth factor gene (Hgf) and the D5Mit66 microsatellite. The following order was defined: (centromere) - Cch12a/Hgf-D5Mit1-D5Nam1/D5-Nam2-rl/D5Mit61-D5Mit72-Xmv45-Htr5a-Peplb-D5Nam3-D5Mit66. Estimated distances between reeler and the nearest flanking markers D5Nam1 and D5Mit72 are 1.5 and 1.0 cM, respectively (95% confidence level), suggesting that the region could be physically mapped using a manageable number of YAC clones.

  5. Empirical Bayesian LASSO-logistic regression for multiple binary trait locus mapping

    PubMed Central

    2013-01-01

    Background Complex binary traits are influenced by many factors including the main effects of many quantitative trait loci (QTLs), the epistatic effects involving more than one QTLs, environmental effects and the effects of gene-environment interactions. Although a number of QTL mapping methods for binary traits have been developed, there still lacks an efficient and powerful method that can handle both main and epistatic effects of a relatively large number of possible QTLs. Results In this paper, we use a Bayesian logistic regression model as the QTL model for binary traits that includes both main and epistatic effects. Our logistic regression model employs hierarchical priors for regression coefficients similar to the ones used in the Bayesian LASSO linear model for multiple QTL mapping for continuous traits. We develop efficient empirical Bayesian algorithms to infer the logistic regression model. Our simulation study shows that our algorithms can easily handle a QTL model with a large number of main and epistatic effects on a personal computer, and outperform five other methods examined including the LASSO, HyperLasso, BhGLM, RVM and the single-QTL mapping method based on logistic regression in terms of power of detection and false positive rate. The utility of our algorithms is also demonstrated through analysis of a real data set. A software package implementing the empirical Bayesian algorithms in this paper is freely available upon request. Conclusions The EBLASSO logistic regression method can handle a large number of effects possibly including the main and epistatic QTL effects, environmental effects and the effects of gene-environment interactions. It will be a very useful tool for multiple QTLs mapping for complex binary traits. PMID:23410082

  6. Bayesian Quantitative Trait Locus Mapping Based on Reconstruction of Recent Genetic Histories

    PubMed Central

    Gasbarra, Dario; Pirinen, Matti; Sillanpää, Mikko J.; Arjas, Elja

    2009-01-01

    We assume that quantitative measurements on a considered trait and unphased genotype data at certain marker loci are available on a sample of individuals from a background population. Our goal is to map quantitative trait loci by using a Bayesian model that performs, and makes use of, probabilistic reconstructions of the recent unobserved genealogical history (a pedigree and a gene flow at the marker loci) of the sampled individuals. This work extends variance component-based linkage analysis to settings where the unobserved pedigrees are considered as latent variables. In addition to the measured trait values and unphased genotype data at the marker loci, the method requires as an input estimates of the population allele frequencies and of a marker map, as well as some parameters related to the population size and the mating behavior. Given such data, the posterior distribution of the trait parameters (the number, the locations, and the relative variance contributions of the trait loci) is studied by using the reversible-jump Markov chain Monte Carlo methodology. We also introduce two shortcuts related to the trait parameters that allow us to do analytic integration, instead of stochastic sampling, in some parts of the algorithm. The method is tested on two simulated data sets. Comparisons with traditional variance component linkage analysis and association analysis demonstrate the benefits of our approach in a gene mapping context. PMID:19620396

  7. Generation of a transcription map from the 17q21 region containing the BRCA1 locus

    SciTech Connect

    Rommens, J.M.; McArthur, J.; Allen, T.

    1994-09-01

    A limited interval of the chromosome 17q21 has been implicated in hereditary breast and ovarian cancer by linkage analysis. The type I 17{beta}-hydroxysteriod dehydrogenase gene (17{beta}HSD) was used to isolate two YACs. These and additional YACs identified with nearby genetic markers were characterized to obtain a detailed physical map of the BRCA1 region. This map provided the basis for the generation of a transcription map in order to identify candidate genes that could be assessed for involvement in the development of breast cancer in affected families. Direct selection of cDNAs from the genomic clones was carried out by hybridization with primary cDNA pools that had been prepared from RNA of mammary gland, ovary, placenta and the Caco-2 colon carcinoma cell line. The selected material was amplified by the polymerase chain reaction and cloned into plasmid vectors. Individual clones of the libraries of the retrieved fragments were then characterized by physical mapping, by RNA hybridization and by sequence analysis. To date, 36 unique cDNA fragments have been mapped to this region and confirmed to originate from chromosome 17. Longer cDNAs were also isolated by screening libraries derived from human breast and placenta. Based on analyses of these clones we have evidence for at least 12 genes from a 1 Megabase region. These include the type I 17{beta}HSD gene and the human {gamma}-tubulin gene. Sequences of two of the cDNA fragments showed similarity to a human brain cDNA and to a human pancreas cDNA. The predicted coding portion of one cDNA showed similarity with a rat ribosomal protein. Also, one cDNA fragment was found to be part of the recently identified gene corresponding to the CA125 antigen. The sequences of the remaining clones showed no strong similarity to known genes or proteins. These cDNAs are being analyzed by DNA and RNA hybridization for aberrations in breast and ovarian cancers.

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

    PubMed

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

    2006-09-01

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

  9. A Transcript Map for the 2.8-Mb Region Containing the Multiple Endocrine Neoplasia Type 1 Locus

    PubMed Central

    Guru, Siradanahalli C.; Agarwal, Sunita K.; Manickam, Pachiappan; Olufemi, Shodimu-Emmanuel; Crabtree, Judy S.; Weisemann, Jane M.; Kester, Mary Beth; Kim, Young S.; Wang, Yingping; Emmert-Buck, Michael R.; Liotta, Lance A.; Spiegel, Allen M.; Boguski, Mark S.; Roe, Bruce A.; Collins, Francis S.; Marx, Stephen J.; Burns, Lee; Chandrasekharappa, Settara C.

    1997-01-01

    Multiple endocrine neoplasia type 1 (MEN 1) is an inherited cancer syndrome in which affected individuals develop multiple parathyroid, enteropancreatic, and pituitary tumors. The locus for MEN1 is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis places the MEN1 gene within a 2-Mb interval flanked by the markers D11S1883 and D11S449. Loss of heterozygosity studies in MEN 1 and sporadic tumors suggest that the MEN1 gene encodes a tumor suppressor and have helped to narrow the location of the gene to a 600-kb interval between PYGM and D11S449. Focusing on this smaller MEN1 interval, we have identified and mapped 12 transcripts to this 600-kb region. A precise ordered map of 33 transcripts, including 12 genes known to map to this region, was generated for the 2.8-Mb D11S480–D11S913 interval. Fifteen candidate genes (of which 10 were examined exhaustively) were evaluated by Southern blot and/or dideoxy fingerprinting analysis to identify the gene harboring disease-causing mutations. [The sequence data described in this paper have been submitted to GenBank under accession nos. EST06996, U93236, AF001540–AF001547, AF001433–AF001436, AF001891–AF001893, N55476, R19205, and W37647 (see Table 1 for listing of transcripts). The BAC clone sequences have been submitted to GenBank under accession nos. AC000134, AC000159, and AC000353.] PMID:9253601

  10. Genetic architecture of contemporary adaptation to biotic invasions: quantitative trait locus mapping of beak reduction in soapberry bugs.

    PubMed

    Yu, Y; Andrés, Jose A

    2014-02-19

    Biological invasions can result in new selection pressures driven by the establishment of new biotic interactions. The response of exotic and native species to selection depends critically on the genetic architecture of ecologically relevant traits. In the Florida peninsula, the soapberry bug (Jadera haematoloma) has colonized the recently introduced Chinese flametree, Koelreuteria elegans, as a host plant. Driven by feeding efficiency, the populations associated with this new host have differentiated into a new bug ecomorph characterized by short beaks more appropriate for feeding on the flattened pods of the Chinese flametree. In this study, we have generated a three-generation pedigree from crossing the long-beaked and short-beaked ecomorphs to construct a de novo linkage map and to locate putative quantitative trait locus (QTL) controlling beak length and body size in J. haematoloma. Using amplified fragment-length polymorphism markers and a two-way pseudo-testcross design, we have produced two parental maps in six linkage groups, covering the known number of chromosomes. QTL analysis revealed one significant QTL for beak length on a maternal linkage group and the corresponding paternal linkage group. Three QTL were found for body size. Through single marker regression analysis, nine single markers that could not be placed on the map were also found to be significantly associated with one or both of the two traits. Interestingly, the most significant body size QTL co-localized with the beak length QTL, suggesting linkage disequilibrium or pleiotropic effects of related traits. Our results suggest an oligogenic control of beak length.

  11. Genetic Architecture of Contemporary Adaptation to Biotic Invasions: Quantitative Trait Locus Mapping of Beak Reduction in Soapberry Bugs

    PubMed Central

    Yu, Y.; Andrés, Jose A.

    2013-01-01

    Biological invasions can result in new selection pressures driven by the establishment of new biotic interactions. The response of exotic and native species to selection depends critically on the genetic architecture of ecologically relevant traits. In the Florida peninsula, the soapberry bug (Jadera haematoloma) has colonized the recently introduced Chinese flametree, Koelreuteria elegans, as a host plant. Driven by feeding efficiency, the populations associated with this new host have differentiated into a new bug ecomorph characterized by short beaks more appropriate for feeding on the flattened pods of the Chinese flametree. In this study, we have generated a three-generation pedigree from crossing the long-beaked and short-beaked ecomorphs to construct a de novo linkage map and to locate putative quantitative trait locus (QTL) controlling beak length and body size in J. haematoloma. Using amplified fragment-length polymorphism markers and a two-way pseudo-testcross design, we have produced two parental maps in six linkage groups, covering the known number of chromosomes. QTL analysis revealed one significant QTL for beak length on a maternal linkage group and the corresponding paternal linkage group. Three QTL were found for body size. Through single marker regression analysis, nine single markers that could not be placed on the map were also found to be significantly associated with one or both of the two traits. Interestingly, the most significant body size QTL co-localized with the beak length QTL, suggesting linkage disequilibrium or pleiotropic effects of related traits. Our results suggest an oligogenic control of beak length. PMID:24347624

  12. Genetic mapping reveals that sinefungin resistance in Toxoplasma gondii is controlled by a putative amino acid transporter locus that can be used as a negative selectable marker.

    PubMed

    Behnke, Michael S; Khan, Asis; Sibley, L David

    2015-02-01

    Quantitative trait locus (QTL) mapping studies have been integral in identifying and understanding virulence mechanisms in the parasite Toxoplasma gondii. In this study, we interrogated a different phenotype by mapping sinefungin (SNF) resistance in the genetic cross between type 2 ME49-FUDR(r) and type 10 VAND-SNF(r). The genetic map of this cross was generated by whole-genome sequencing of the progeny and subsequent identification of single nucleotide polymorphisms (SNPs) inherited from the parents. Based on this high-density genetic map, we were able to pinpoint the sinefungin resistance phenotype to one significant locus on chromosome IX. Within this locus, a single nonsynonymous SNP (nsSNP) resulting in an early stop codon in the TGVAND_290860 gene was identified, occurring only in the sinefungin-resistant progeny. Using CRISPR/CAS9, we were able to confirm that targeted disruption of TGVAND_290860 renders parasites sinefungin resistant. Because disruption of the SNR1 gene confers resistance, we also show that it can be used as a negative selectable marker to insert either a positive drug selection cassette or a heterologous reporter. These data demonstrate the power of combining classical genetic mapping, whole-genome sequencing, and CRISPR-mediated gene disruption for combined forward and reverse genetic strategies in T. gondii.

  13. Mapping of a genetic locus that affects glycerol 3-phosphate transport in Bacillus subtilis.

    PubMed Central

    Lindgren, V

    1978-01-01

    Two types of fosfomycin-resistant mutants of Bacillus subtilis were isolated. Mutants of the first type (GlpT mutants) were resistant to at least 200 microgram of fosfomycin per ml and failed to take up exogenous glycerol 3-phosphate. Mutants of the second type were resistant to lower concentrations of fosfomycin and transported glycerol-3-phosphate as efficiently as wild-type bacteria. The glpT mutations, but not the mutations in the second type of fosfomycin-resistant mutants, map in the cysA-aroI region of the B. subtilis chromosome. PMID:415047

  14. Physical mapping of the IGF2 locus in the South American opossum Monodelphis domestica.

    PubMed

    Lawton, B R; Obergfell, C; O'Neill, R J; O'Neill, M J

    2007-01-01

    The South American opossum Monodelphis domestica has been a model organism for marsupials for many years and has recently been the subject of a large-scale genome sequencing effort that will provide the foundation for comparative studies of gene function and regulation. Genomic imprinting is one mechanism of gene regulation that has received increasing attention due to the impact of imprinting defects on development and disease. We have mapped the imprinted insulin-like growth factor II (IGF2) gene of M. domestica as a first step in understanding the regulatory mechanisms involved in genomic imprinting in this marsupial.

  15. Obese Locus in WNIN/Obese Rat Maps on Chromosome 5 Upstream of Leptin Receptor

    PubMed Central

    Kalashikam, Rajender Rao; Battula, Kiran Kumar; Kirlampalli, Veerababu; Friedman, Jeffrey M.; Nappanveettil, Giridharan

    2013-01-01

    WNIN/Obese (WNIN/Ob) rat a new mutant model of metabolic syndrome was identified in 1996 from an inbred Wistar rat strain, WNIN. So far several papers are published on this model highlighting its physical, biochemical and metabolic traits. WNIN/Ob is leptin resistant with unaltered leptin or its receptor coding sequences - the two well-known candidate genes for obesity. Genotyping analysis of F2 progeny (raised from WNIN/Ob × Fisher - 344) in the present study localized the mutation to a recombinant region of 14.15cM on chromosome 5. This was further corroborated by QTL analysis for body weight, which narrowed this region to 4.43 cM with flanking markers D5Rat256 & D5Wox37. Interval mapping of body weight QTL shows that the LOD score peak maps upstream of leptin receptor and shows an additive effect suggesting this as a novel mutation and signifying the model as a valuable resource for studies on obesity and metabolic syndrome. PMID:24204914

  16. The human HNRPD locus maps to 4q21 and encodes a highly conserved protein.

    PubMed

    Dempsey, L A; Li, M J; DePace, A; Bray-Ward, P; Maizels, N

    1998-05-01

    The hnRNP D protein interacts with nucleic acids both in vivo and in vitro. Like many other proteins that interact with RNA, it contains RBD (or "RRM") domains and arg-gly-gly (RGG) motifs. We have examined the organization and localization of the human and murine genes that encode the hnRNP D protein. Comparison of the predicted sequences of the hnRNP D proteins in human and mouse shows that they are 96.9% identical (98.9% similar). This very high level of conservation suggests a critical function for hnRNP D. Sequence analysis of the human HNRPD gene shows that the protein is encoded by eight exons and that two additional exons specify sequences in the 3' UTR. Use of two of the coding exons is determined by alternative splicing of the HNRPD mRNA. The human HNRPD gene maps to 4q21. The mouse Hnrpd gene maps to the F region of chromosome 3, which is syntenic with the human 4q21 region.

  17. Evidence for a locus regulating total serum IgE levels mapping to chromosome 5

    SciTech Connect

    Meyers, D.A.; Xu, J.; Levitt, R.C.

    1994-09-15

    Genetic studies of total serum IgE levels were preformed since high IgE levels correlate with clinical expression of allergy and asthma. Families ascertained through a parent with asthma were genotyped for markers on 5q where there are multiple candidate genes that may influence the control of IgE and inflammation. Evidence for linkage of the IgE phenotype to 5q was obtained by both sib-pair and lod score analysis with evidence for recessive inheritance of high IgE levels from segregation analysis. These findings represent a major step in mapping genes important in the regulation of allergic responses and the pathogenesis of asthma. 52 refs., 3 tabs.

  18. Construction of a High-Density Genetic Map Based on Large-Scale Marker Development in Mango Using Specific-Locus Amplified Fragment Sequencing (SLAF-seq)

    PubMed Central

    Luo, Chun; Shu, Bo; Yao, Quangsheng; Wu, Hongxia; Xu, Wentian; Wang, Songbiao

    2016-01-01

    Genetic maps are particularly important and valuable tools for quantitative trait locus (QTL) mapping and marker assisted selection (MAS) of plant with desirable traits. In this study, 173 F1 plants from a cross between Mangifera indica L. “Jin-Hwang” and M. indica L. “Irwin” and their parent plants were subjected to high-throughput sequencing and specific-locus amplified fragment (SLAF) library construction. After preprocessing, 66.02 Gb of raw data containing 330.64 M reads were obtained. A total of 318,414 SLAFs were detected, of which 156,368 were polymorphic. Finally, 6594 SLAFs were organized into a linkage map consisting of 20 linkage groups (LGs). The total length of the map was 3148.28 cM and the average distance between adjacent markers was 0.48 cM. This map could be considered, to our knowledge, the first high-density genetic map of mango, and might form the basis for fine QTL mapping and MAS of mango. PMID:27625670

  19. 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.

  20. Positional cloning of the nude locus: Genetic, physical, and transcription maps of the region and mutations in the mouse and rat

    SciTech Connect

    Segre, J.A.; Lander, E.S. |; Taylor, B.A.

    1995-08-10

    Mutations in the nude locus in mice and rats produce the pleiotropic phenotype of hairlessness and athymia, resulting in severely compromised immune system. To identify the causative gene, we utilized modern tools and techniques of positional cloning. Specifically, spanning the region in which the nude locus resides, we constructed a genetic map of polymorphic markers, a physical map of yeast artificial chromosomes and bacteriophage P1 clones, and a transcription map of genes obtained by direct cDNA selection and exon trapping. We identified seven novel transcripts with similarity to genes from Drosophila, Caenorhabditis elegans, rat or human and three previously identified mouse genes. Based on our transcription mapping results, we present a novel approach to estimate that the nude locus resides in a region approximately threefold enriched for genes. We confirm a recently published report that the nude phenotype is caused by mutations in a gene encoding a novel winged helix or fork head domain transcription factor, whn. We report as well as the mutations in the rat rnu allele and the complete coding sequence of the rat whn mRNA. 42 refs., 4 figs., 1 tab.

  1. Fine mapping of RBG2, a quantitative trait locus for resistance to Burkholderia glumae, on rice chromosome 1.

    PubMed

    Mizobuchi, Ritsuko; Sato, Hiroyuki; Fukuoka, Shuichi; Tsushima, Seiya; Yano, Masahiro

    Bacterial grain rot (BGR), caused by the bacterial pathogen Burkholderia glumae, is a destructive disease of rice. At anthesis, rice panicles are attacked by the pathogen, and the infection causes unfilled or aborted grains, reducing grain yield and quality. Thus, increasing the level of BGR resistance is an important objective for rice breeding. A quantitative trait locus (QTL) on rice chromosome 1 that controls BGR resistance was previously detected in backcross inbred lines (BILs) derived from a cross between Kele, a resistant traditional lowland cultivar (indica) that originated in India, and Hitomebore, a susceptible modern lowland cultivar (temperate japonica) from Japan. Further genetic analyses using a BC3F6 population derived from a cross between a resistant BIL (BC2F5) and Hitomebore confirmed that a QTL for BGR resistance was located on the long arm of chromosome 1. To define more precisely the chromosomal region underlying this QTL, we identified nine BC2F6 plants in which recombination occurred near the QTL. Substitution mapping using homozygous recombinant and nonrecombinant plants demonstrated that the QTL, here designated as Resistance to Burkholderia glumae 2 (RBG2), was located in a 502-kb interval defined by simple sequence repeat markers RM1216 and RM11727.

  2. Expression quantitative trait locus mapping across water availability environments reveals contrasting associations with genomic features in Arabidopsis.

    PubMed

    Lowry, David B; Logan, Tierney L; Santuari, Luca; Hardtke, Christian S; Richards, James H; DeRose-Wilson, Leah J; McKay, John K; Sen, Saunak; Juenger, Thomas E

    2013-09-01

    The regulation of gene expression is crucial for an organism's development and response to stress, and an understanding of the evolution of gene expression is of fundamental importance to basic and applied biology. To improve this understanding, we conducted expression quantitative trait locus (eQTL) mapping in the Tsu-1 (Tsushima, Japan) × Kas-1 (Kashmir, India) recombinant inbred line population of Arabidopsis thaliana across soil drying treatments. We then used genome resequencing data to evaluate whether genomic features (promoter polymorphism, recombination rate, gene length, and gene density) are associated with genes responding to the environment (E) or with genes with genetic variation (G) in gene expression in the form of eQTLs. We identified thousands of genes that responded to soil drying and hundreds of main-effect eQTLs. However, we identified very few statistically significant eQTLs that interacted with the soil drying treatment (GxE eQTL). Analysis of genome resequencing data revealed associations of several genomic features with G and E genes. In general, E genes had lower promoter diversity and local recombination rates. By contrast, genes with eQTLs (G) had significantly greater promoter diversity and were located in genomic regions with higher recombination. These results suggest that genomic architecture may play an important a role in the evolution of gene expression.

  3. Fine mapping of a quantitative trait locus for bovine milk fat composition on Bos taurus autosome 19.

    PubMed

    Bouwman, Aniek C; Visker, Marleen H P W; van Arendonk, Johana M; Bovenhuis, Henk

    2014-02-01

    A major quantitative trait locus (QTL) for milk fat content and fatty acids in both milk and adipose tissue has been detected on Bos taurus autosome 19 (BTA19) in several cattle breeds. The objective of this study was to refine the location of the QTL on BTA19 for bovine milk fat composition using a denser set of markers. Opportunities for fine mapping were provided by imputation from 50,000 genotyped single nucleotide polymorphisms (SNP) toward a high-density SNP panel with up to 777,000 SNP. The QTL region was narrowed down to a linkage disequilibrium block formed by 22 SNP covering 85,007 bp, from 51,303,322 to 51,388,329 bp on BTA19. This linkage disequilibrium block contained 2 genes: coiled-coil domain containing 57 (CCDC57) and fatty acid synthase (FASN). The gene CCDC57 is minimally characterized and has not been associated with bovine milk fat previously, but is expressed in the mammary gland. The gene FASN has been associated with bovine milk fat and fat in adipose tissue before. This gene is a likely candidate for the QTL on BTA19 because of its involvement in de novo fat synthesis. Future studies using sequence data of both CCDC57 and FASN, and eventually functional studies, will have to be pursued to assign the causal variant(s). Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  4. Genomewide search for dehydrated hereditary stomatocytosis (hereditary xerocytosis): mapping of locus to chromosome 16 (16q23-qter).

    PubMed Central

    Carella, M; Stewart, G; Ajetunmobi, J F; Perrotta, S; Grootenboer, S; Tchernia, G; Delaunay, J; Totaro, A; Zelante, L; Gasparini, P; Iolascon, A

    1998-01-01

    Dehydrated hereditary stomatocytosis, also known as "hereditary xerocytosis," is caused by a red blood cell-membrane defect characterized by stomatocytic morphology, increased mean corpuscular hemoglobin concentration, decreased osmotic fragility, increased permeability to the univalent cations Na+ and K+, and an increased proportion of phosphatidylcholine in the membrane. The clinical presentation is heterogeneous, ranging from mild to moderate hemolytic anemia associated with scleral icterus, splenomegaly, and choletithiasis. Iron overload may develop later in life. The disease is transmitted as an autosomal dominant trait. We recruited a large three-generation Irish family affected with DHS and comprising 23 members, of whom 14 were affected and 9 were healthy. Two additional, small families also were included in the study. The DNA samples from the family members were used in a genomewide search to identify, by linkage analysis, the DHS locus. After the exclusion of a portion of the human genome, we obtained conclusive evidence for linkage of DHS to microsatellite markers on the long arm of chromosome 16 (16q23-q24). A maximum two-point LOD score of 6.62 at recombination fraction .00 was obtained with marker D16S520. There are no recombination events defining the telomeric limit of the region, which therefore is quite large. No candidate genes map to this area. PMID:9718354

  5. Genomewide search for dehydrated hereditary stomatocytosis (hereditary xerocytosis): mapping of locus to chromosome 16 (16q23-qter).

    PubMed

    Carella, M; Stewart, G; Ajetunmobi, J F; Perrotta, S; Grootenboer, S; Tchernia, G; Delaunay, J; Totaro, A; Zelante, L; Gasparini, P; Iolascon, A

    1998-09-01

    Dehydrated hereditary stomatocytosis, also known as "hereditary xerocytosis," is caused by a red blood cell-membrane defect characterized by stomatocytic morphology, increased mean corpuscular hemoglobin concentration, decreased osmotic fragility, increased permeability to the univalent cations Na+ and K+, and an increased proportion of phosphatidylcholine in the membrane. The clinical presentation is heterogeneous, ranging from mild to moderate hemolytic anemia associated with scleral icterus, splenomegaly, and choletithiasis. Iron overload may develop later in life. The disease is transmitted as an autosomal dominant trait. We recruited a large three-generation Irish family affected with DHS and comprising 23 members, of whom 14 were affected and 9 were healthy. Two additional, small families also were included in the study. The DNA samples from the family members were used in a genomewide search to identify, by linkage analysis, the DHS locus. After the exclusion of a portion of the human genome, we obtained conclusive evidence for linkage of DHS to microsatellite markers on the long arm of chromosome 16 (16q23-q24). A maximum two-point LOD score of 6.62 at recombination fraction .00 was obtained with marker D16S520. There are no recombination events defining the telomeric limit of the region, which therefore is quite large. No candidate genes map to this area.

  6. Generation of a transcription map at the HSD17B locus centromeric to BRCA1 at 17q21

    SciTech Connect

    Rommens, J.M.; McArthur, J.; Allen, T.

    1995-08-10

    A detailed transcription map of the 320-kb region containing the HSD17B locus on chromosome 17 was generated. Thirty unique cDNA fragments, retrieved following the hybridization of immobilized YACs to primary pools of cDNAs prepared from RNA of mammary gland, ovary, placenta, and the Caco-2 cell line, were aligned into 10 transcription units by physical mapping and hybridization to RNAs of a series of tissues. The cDNAs were then further characterized by sequencing and used to screen mammary gland DNA libraries. Fragments corresponding to the broadly expressed {gamma}-tubulin and Ki antigen genes were identified. A full-length cDNA clone encoding a 117-amino-acid protein homologous to the rat ribosomal protein L34 was isolated. Portions of genes with restricted patterns of expression were also obtained, including the previously characterized HSD17B1. One new gene, for which a full-length cDNA was isolated, was found to have an interesting tissue-specific pattern of expression with abundant mRNA in both the colon and the testis and in the mammary carcinoma cell line BT-474. This contrasted with the barely detectable level observed in several tissues including normal mammary gland. Of the five additional transcription units identified, one showed no similarity, two showed identity to human expressed sequences, and two displayed similarity to genes of animal species by amino acid alignment. These latter cDNA clones include potential homologues of a rat nuclear tyrosine phosphatase and of a factor of Drosophila that is known to be involved in the negative regulation of transcription of segment identity genes. 44 refs., 7 figs., 1 tab.

  7. Mapping and characterization of mutations induced by benzo[a]pyrene diol epoxide at dihydrofolate reductase locus in CHO cells.

    PubMed

    Carothers, A M; Urlaub, G; Grunberger, D; Chasin, L A

    1988-03-01

    Chinese hamster ovary cells were mutagenized with benzo[a]pyrene diol epoxide (BPDE), an aromatic hydrocarbon carcinogen, and mutants at the dihydrofolate reductase (dhfr) locus were isolated. Of 15 mutants analyzed by Southern blotting, one contained a large deletion that spanned all six exons of the 25-kb dhfr gene; the remaining mutants exhibited no detectable changes. Three of these putative point mutations were localized by the loss of a restriction site: a SacI site in exon III, an MspI site in exon III, and a KpnI site in exon VI. The affected regions in two of these mutants were cloned and sequenced. The SacI- mutant was caused by a G:C----T:A transversion resulting in an amber termination codon. In the MspI- mutant, the deletion of a single C:G resulted in a frameshift and a downstream ochre termination codon. On the basis of overlapping restriction site sequences, the KpnI- mutant was deduced to be a splicing mutant involving the most 3' G in intron V. The location of these and the remaining 11 putative point mutations was sought using RNA heteroduplex mapping. Mismatched bases between riboprobes complementary to wild-type dhfr mRNA and mutant mRNA molecules were detected in 10 of the 14 mutants analyzed. These mutations mapped to four of the six exons or exon splice sites. Surprisingly, over half of these mutants exhibited greatly reduced (approximately 10-fold) steady-state levels of dhfr mRNA.

  8. Quantitative trait locus mapping identifies candidate alleles involved in adaptive introgression and range expansion in a wild sunflower.

    PubMed

    Whitney, Kenneth D; Broman, Karl W; Kane, Nolan C; Hovick, Stephen M; Randell, Rebecca A; Rieseberg, Loren H

    2015-05-01

    The wild North American sunflowers Helianthus annuus and H. debilis are participants in one of the earliest identified examples of adaptive trait introgression, and the exchange is hypothesized to have triggered a range expansion in H. annuus. However, the genetic basis of the adaptive exchange has not been examined. Here, we combine quantitative trait locus (QTL) mapping with field measurements of fitness to identify candidate H. debilis QTL alleles likely to have introgressed into H. annuus to form the natural hybrid lineage H. a. texanus. Two 500-individual BC1 mapping populations were grown in central Texas, genotyped for 384 single nucleotide polymorphism (SNP) markers and then phenotyped in the field for two fitness and 22 herbivore resistance, ecophysiological, phenological and architectural traits. We identified a total of 110 QTL, including at least one QTL for 22 of the 24 traits. Over 75% of traits exhibited at least one H. debilis QTL allele that would shift the trait in the direction of the wild hybrid H. a. texanus. We identified three chromosomal regions where H. debilis alleles increased both female and male components of fitness; these regions are expected to be strongly favoured in the wild. QTL for a number of other ecophysiological, phenological and architectural traits colocalized with these three regions and are candidates for the actual traits driving adaptive shifts. G × E interactions played a modest role, with 17% of the QTL showing potentially divergent phenotypic effects between the two field sites. The candidate adaptive chromosomal regions identified here serve as explicit hypotheses for how the genetic architecture of the hybrid lineage came into existence.

  9. A SOS3 homologue maps to HvNax4, a barley locus controlling an environmentally sensitive Na+ exclusion trait

    PubMed Central

    Rivandi, J.; Miyazaki, J.; Hrmova, M.; Pallotta, M.; Tester, M.; Collins, N. C.

    2011-01-01

    Genes that enable crops to limit Na+ accumulation in shoot tissues represent potential sources of salinity tolerance for breeding. In barley, the HvNax4 locus lowered shoot Na+ content by between 12% and 59% (g−1 DW), or not at all, depending on the growth conditions in hydroponics and a range of soil types, indicating a strong influence of environment on expression. HvNax4 was fine-mapped on the long arm of barley chromosome 1H. Corresponding intervals of ∼200 kb, containing a total of 34 predicted genes, were defined in the sequenced rice and Brachypodium genomes. HvCBL4, a close barley homologue of the SOS3 salinity tolerance gene of Arabidopsis, co-segregated with HvNax4. No difference in HvCBL4 mRNA expression was detected between the mapping parents. However, genomic and cDNA sequences of the HvCBL4 alleles were obtained, revealing a single Ala111Thr amino acid substitution difference in the encoded proteins. The known crystal structure of SOS3 was used as a template to obtain molecular models of the barley proteins, resulting in structures very similar to that of SOS3. The position in SOS3 corresponding to the barley substitution does not participate directly in Ca2+ binding, post-translational modifications or interaction with the SOS2 signalling partner. However, Thr111 but not Ala111 forms a predicted hydrogen bond with a neighbouring α-helix, which has potential implications for the overall structure and function of the barley protein. HvCBL4 therefore represents a candidate for HvNax4 that warrants further investigation. PMID:21047983

  10. Genetics and mapping of a new anthracnose resistance locus in Andean common bean Paloma.

    PubMed

    de Lima Castro, Sandra Aparecida; Gonçalves-Vidigal, Maria Celeste; Gilio, Thiago Alexandre Santana; Lacanallo, Giselly Figueiredo; Valentini, Giseli; da Silva Ramos Martins, Vanusa; Song, Qijian; Galván, Marta Zulema; Hurtado-Gonzales, Oscar P; Pastor-Corrales, Marcial Antonio

    2017-04-18

    The Andean cultivar Paloma is resistant to Mesoamerican and Andean races of Colletotrichum lindemuthianum, the fungal pathogen that causes the destructive anthracnose disease in common bean. Remarkably, Paloma is resistant to Mesoamerican races 2047 and 3481, which are among the most virulent races of the anthracnose pathogen. Most genes conferring anthracnose resistance in common bean are overcome by these races. The genetic mapping and the relationship between the resistant Co-Pa gene of Paloma and previously characterized anthracnose resistance genes can be a great contribution for breeding programs. The inheritance of resistance studies for Paloma was performed in F2 population from the cross Paloma (resistant) × Cornell 49-242 (susceptible) inoculated with race 2047, and in F2 and F2:3 generations from the cross Paloma (resistant) × PI 207262 (susceptible) inoculated with race 3481. The results of these studies demonstrated that a single dominant gene confers the resistance in Paloma. Allelism tests performed with multiple races of C. lindemuthianum showed that the resistance gene in Paloma, provisionally named Co-Pa, is independent from the anthracnose resistance genes Co-1, Co-2, Co-3, Co-4, Co-5, Co-6, Co-12, Co-13, Co-14, Co-15 and Co-16. Bulk segregant analysis using the SNP chip BARCBean6K_3 positioned the approximate location of Co-Pa in the lower arm of chromosome Pv01. Further mapping analysis located the Co-Pa gene at a 390 kb region of Pv01 flanked by SNP markers SS82 and SS83 at a distance of 1.3 and 2.1 cM, respectively. The results presented here showed that Paloma cultivar has a new dominant gene conferring resistance to anthracnose, which is independent from those genes previously described. The linkage between the Co-Pa gene and the SS82 and SS83 SNP markers will be extremely important for marker-assisted introgression of the gene into elite cultivars in order to enhance resistance.

  11. A putative vulnerability locus to multiple sclerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2.

    PubMed

    Kuokkanen, S; Sundvall, M; Terwilliger, J D; Tienari, P J; Wikström, J; Holmdahl, R; Pettersson, U; Peltonen, L

    1996-08-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder characterized by multifocal damage of myelin in the central nervous system (CNS). The prevalence of this putative autoimmune disease is 0.1% in individuals of northern European origin. Family, adoption and twin studies implicate genetic factors in the aetiology. MS is widely speculated to be a multifactorial disorder with a complex mode of inheritance. Despite many studies of candidate genes, only an association with HLA-DR2-DQ6 has been generally detected, and the number of susceptibility genes remains unknown. The chronic variant of experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune disease in rodents, represents a relevant animal model for MS given the chronic relapsing disease course and inflammatory changes of CNS observed in these demyelinating disorders. Susceptibility to EAE is also influenced by the major histocompatibility complex (MHC). Human syntenic regions to murine loci predisposing to EAE were tested as candidate regions for genetic susceptibility of MS. Three chromosomal regions (1p22-q23, 5p14-p12 and Xq13.2-q22) were screened in 21 Finnish multiplex MS families most originating from a high risk region in western Finland. Several markers yielded positive lod scores on 5p14-p12, syntenic to the murine locus Eae2. Our data provide evidence for a predisposing locus for MS on 5p14-p12.

  12. A method for developing high-density SNP maps and its application at the type 1 angiotensin II receptor (AGTR1) locus.

    PubMed

    Antonellis, Anthony; Rogus, John J; Canani, Luis H; Makita, Yuchiro; Pezzolesi, Marcus G; Nam, MoonSuk; Ng, Daniel; Moczulski, Dariusz; Warram, James H; Krolewski, Andrzej S

    2002-03-01

    Evaluating the potential genetic components of complex disease will likely be aided through the use of dense polymorphism maps. Previously, we reported evidence for linkage with diabetic nephropathy on chromosome 3q in a region encompassing the type 1 angiotensin II receptor (AGTR1) gene. To further investigate any role for this gene in disease onset, we set out to design a dense polymorphism map spanning the AGTR1 locus for the purpose of association studies. Toward this goal, we have developed a technique for rapid identification of polymorphisms in long stretches of genomic DNA. This approach uses long-range PCR, DNA pooling, and transposon-based DNA sequencing. Using this technique, we efficiently validated and genotyped 18 polymorphisms spanning the 60.5-kb AGTR1 locus. Our panel of polymorphisms has an average spacing of 3.2 kb and an average minor allele frequency of 24%.

  13. Fine Mapping Links the FTa1 Flowering Time Regulator to the Dominant Spring1 Locus in Medicago

    PubMed Central

    Yeoh, Chin Chin; Balcerowicz, Martin; Zhang, Lulu; Jaudal, Mauren; Brocard, Lysiane; Ratet, Pascal; Putterill, Joanna

    2013-01-01

    To extend our understanding of flowering time control in eudicots, we screened for mutants in the model legume Medicago truncatula (Medicago). We identified an early flowering mutant, spring1, in a T-DNA mutant screen, but spring1 was not tagged and was deemed a somaclonal mutant. We backcrossed the mutant to wild type R108. The F1 plants and the majority of F2 plants were early flowering like spring1, strongly indicating that spring1 conferred monogenic, dominant early flowering. We hypothesized that the spring1 phenotype resulted from over expression of an activator of flowering. Previously, a major QTL for flowering time in different Medicago accessions was located to an interval on chromosome 7 with six candidate flowering- time activators, including a CONSTANS gene, MtCO, and three FLOWERING LOCUS T (FT) genes. Hence we embarked upon linkage mapping using 29 markers from the MtCO/FT region on chromosome 7 on two populations developed by crossing spring1 with Jester. Spring1 mapped to an interval of ∼0.5 Mb on chromosome 7 that excluded MtCO, but contained 78 genes, including the three FT genes. Of these FT genes, only FTa1 was up-regulated in spring1 plants. We then investigated global gene expression in spring1 and R108 by microarray analysis. Overall, they had highly similar gene expression and apart from FTa1, no genes in the mapping interval were differentially expressed. Two MADS transcription factor genes, FRUITFULLb (FULb) and SUPPRESSOR OF OVER EXPRESSION OF CONSTANS1a (SOC1a), that were up-regulated in spring1, were also up-regulated in transgenic Medicago over-expressing FTa1. This suggested that their differential expression in spring1 resulted from the increased abundance of FTa1. A 6255 bp genomic FTa1 fragment, including the complete 5′ region, was sequenced, but no changes were observed indicating that the spring1 mutation is not a DNA sequence difference in the FTa1 promoter or introns. PMID:23308229

  14. Fine-Scale Mapping of the FGFR2 Breast Cancer Risk Locus: Putative Functional Variants Differentially Bind FOXA1 and E2F1

    PubMed Central

    Meyer, Kerstin B.; O’Reilly, Martin; Michailidou, Kyriaki; Carlebur, Saskia; Edwards, Stacey L.; French, Juliet D.; Prathalingham, Radhika; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; de Santiago, Ines; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Van ’t Veer, Laura J.; Hogervorst, Frans B.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Lux, Michael P.; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Zamora, M. Pilar; Arias, Jose I.; Benitez, Javier; Neuhausen, Susan; Anton-Culver, Hoda; Ziogas, Argyrios; Dur, Christina C.; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K.; Engel, Christoph; Ditsch, Nina; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Dörk, Thilo; Helbig, Sonja; Bogdanova, Natalia V.; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Thienpont, Bernard; Christiaens, Marie-Rose; Smeets, Ann; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Bernard, Loris; Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu; Purrington, Kristen; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo-Hwang; Yip, Cheng-Har; Phuah, Sze-Yee; Kristensen, Vessela; Grenaker Alnæs, Grethe; Børresen-Dale, Anne-Lise; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline M.; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Darabi, Hartef; Eriksson, Kimael; Hooning, Maartje J.; Martens, John W.M.; van den Ouweland, Ans M.W.; van Deurzen, Carolien H.M.; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Reed, Malcolm W.R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D.P.; Ghoussaini, Maya; Harrington, Patricia; Tyrer, Jonathan; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Hartman, Mikael; Hui, Miao; Lim, Wei-Yen; Buhari, Shaik A.; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans-Ulrich; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Vachon, Celine; Slager, Susan; Fostira, Florentia; Pilarski, Robert; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Ponder, Bruce A.J.; Dunning, Alison M.; Easton, Douglas F.

    2013-01-01

    The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus. Within risk signals 1 and 3, genetic analysis identified five and two variants, respectively, highly correlated with the most strongly associated SNPs. By using a combination of genetic fine mapping, data on DNase hypersensitivity, and electrophoretic mobility shift assays to study protein-DNA binding, we identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and was able to recruit ERα to this site in an allele-specific manner, whereas E2F1 preferentially bound the risk variant of rs35054928. The risk alleles were preferentially found in open chromatin and bound by Ser5 phosphorylated RNA polymerase II, suggesting that the risk alleles are associated with changes in transcription. Chromatin conformation capture demonstrated that the risk region was able to interact with the promoter of FGFR2, the likely target gene of this risk region. A role for FOXA1 in mediating breast cancer susceptibility at this locus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease. PMID:24290378

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed Central

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

    1994-01-01

    Salla disease (SD), or adult-type free sialic acid storage disease, is an autosomal recessive lysosomal storage disorder characterized by impaired transport of free sialic acid across the lysosomal membrane and severe psychomotor retardation. Random linkage analysis of a sample of 27 Finnish families allowed us to localize the SD locus to the long arm of chromosome 6. The highest lod score of 8.95 was obtained with a microsatellite marker of locus D6S286 at theta = .00. Evidence for linkage disequilibrium was observed between the SD locus and the alleles of three closely linked markers, suggesting that the length of the critical region for the SD locus is in the order of 190 kb. PMID:8198127

  18. Mapping of Trichodermin Resistance in SACCHAROMYCES CEREVISIAE : A Genetic Locus for a Component of the 60s Ribsomal Subunit

    PubMed Central

    Grant, Paul G.; Schindler, Daniel; Davies, Julian E.

    1976-01-01

    Resistance to the protein synthesis inhibitor trichodermin in Saccharomyces cerevisiae has been studied. A single recessive nuclear gene was responsible for resistance. The resistance locus, tcm1 was found to be closely linked (1 centimorgan) to the locus pet 17 on the right arm of chromosome XV. The mutation to trichodermin resistance conferred resistance to other 12,13-epoxytrichothecenes and to the structurally unrelated antibiotic anisomycin. PMID:786781

  19. Inheritance and molecular mapping of Rf6 locus with pollen fertility restoration ability on A1 and A2 cytoplasms in sorghum.

    PubMed

    Praveen, M; Anurag Uttam, G; Suneetha, N; Umakanth, Av; Patil, J V; Madhusudhana, R

    2015-09-01

    Of the several male sterility cytoplasms available as an alternative to the widely exploited A1 (milo) cytoplasm in sorghum, A2 is more suitable for commercial exploitation. Diversification of genetic and cytoplasmic base of hybrids involving A2 cytoplasm necessitates mapping of fertility restorer (Rf) genes for use in marker-assisted restorer development. We mapped a major male fertility restoration locus on sorghum chromosome 4 tightly linked with SSR markers, SB2387 and SB2388. This new fertility locus, Rf6, was able to restore male fertility on both A1 and A2 cytoplasms. Analysis of the genomic region around the Rf6 locus identified six genes including a pentatricopeptide repeat (PPR) gene, Sobic.004G004100. With its similar restoration ability to Rf1, Rf2 and Rf5 loci in sorghum, it is most likely that the Rf6 is a member of the PPR gene family, and the PPR gene Sobic.004G004100 could be a candidate for fertility restoration on A1 and A2 cytoplasms.

  20. Molecular genetics of the brown (b)-locus region of mouse chromosome 4. I. Origin and molecular mapping of radiation- and chemical-induced lethal brown deletions.

    PubMed

    Rinchik, E M; Bell, J A; Hunsicker, P R; Friedman, J M; Jackson, I J; Russell, L B

    1994-07-01

    Over a period of many years, germ-cell mutagenesis experiments using the mouse specific-locus test have generated numerous radiation- and chemical-induced alleles of the brown (b; Tyrp 1) locus in mouse chromosome 4. We describe here the origin, maintenance and initial molecular characterization of 28 b mutations that are prenatally lethal when homozygous. Each of these mutations is deleted for Tyrp 1 sequences, and each of 25 mutations tested further is deleted for at least one other locus defined by molecular clones previously found to be closely linked to b by interspecific backcross analysis. A panel of DNAs from mice carrying a lethal b mutation and a Mus spretus chromosome 4 was used in the fine structure mapping of these molecularly defined loci. The deletional nature of each of these prenatally lethal mutations is consistent with the hypothesis that the null phenotype at b has an effect only on the quality (color) of eumelanin produced in melanocytes. The resulting deletion map provides a framework on which to build future molecular-genetic and biological analyses of this region of mouse chromosome 4.

  1. Long-range restriction map of human chromosome 22q11-22q12 between the lambda immunoglobulin locus and the Ewing sarcoma breakpoint

    SciTech Connect

    McDermid, H.E. ); Budarf, M.L.; Emanuel, B.S. Children's Hospital of Philadelphia, PA )

    1993-11-01

    A long-range restriction map of the region between the immunoglobulin lambda locus and the Ewing sarcoma breakpoint has been constructed using the rare-cutting enzymes NotI, NruI, AscI, and BsiWI. The map spans approximately 11,000 kb and represents about one-fifth of the long arm of chromosome 22. Thirty-nine markers, including seven NotI junction clones as well as numerous genes and anonymous sequences, were mapped to the region with a somatic cell hybrid panel. These probes were then used to produce the map. The seven NotI junction clones each identified a possible CpG island. The breakpoints of the RAJ5 hybrid and the Ewing sarcoma t(11;22) were also localized in the resulting map. This physical map will be useful in studying chromosomal rearrangements in the region, as well as providing the details to examine the fidelity of the YAC and cosmid contigs currently under construction. Comparisons of this physical map to genetic and radiation hybrid maps are discussed. 52 refs., 7 figs., 3 tabs.

  2. A High-Density Genetic Map with Array-Based Markers Facilitates Structural and Quantitative Trait Locus Analyses of the Common Wheat Genome

    PubMed Central

    Iehisa, Julio Cesar Masaru; Ohno, Ryoko; Kimura, Tatsuro; Enoki, Hiroyuki; Nishimura, Satoru; Okamoto, Yuki; Nasuda, Shuhei; Takumi, Shigeo

    2014-01-01

    The large genome and allohexaploidy of common wheat have complicated construction of a high-density genetic map. Although improvements in the throughput of next-generation sequencing (NGS) technologies have made it possible to obtain a large amount of genotyping data for an entire mapping population by direct sequencing, including hexaploid wheat, a significant number of missing data points are often apparent due to the low coverage of sequencing. In the present study, a microarray-based polymorphism detection system was developed using NGS data obtained from complexity-reduced genomic DNA of two common wheat cultivars, Chinese Spring (CS) and Mironovskaya 808. After design and selection of polymorphic probes, 13,056 new markers were added to the linkage map of a recombinant inbred mapping population between CS and Mironovskaya 808. On average, 2.49 missing data points per marker were observed in the 201 recombinant inbred lines, with a maximum of 42. Around 40% of the new markers were derived from genic regions and 11% from repetitive regions. The low number of retroelements indicated that the new polymorphic markers were mainly derived from the less repetitive region of the wheat genome. Around 25% of the mapped sequences were useful for alignment with the physical map of barley. Quantitative trait locus (QTL) analyses of 14 agronomically important traits related to flowering, spikes, and seeds demonstrated that the new high-density map showed improved QTL detection, resolution, and accuracy over the original simple sequence repeat map. PMID:24972598

  3. High-resolution linkage and quantitative trait locus mapping aided by genome survey sequencing: building up an integrative genomic framework for a bivalve mollusc.

    PubMed

    Jiao, Wenqian; Fu, Xiaoteng; Dou, Jinzhuang; Li, Hengde; Su, Hailin; Mao, Junxia; Yu, Qian; Zhang, Lingling; Hu, Xiaoli; Huang, Xiaoting; Wang, Yangfan; Wang, Shi; Bao, Zhenmin

    2014-02-01

    Genetic linkage maps are indispensable tools in genetic and genomic studies. Recent development of genotyping-by-sequencing (GBS) methods holds great promise for constructing high-resolution linkage maps in organisms lacking extensive genomic resources. In the present study, linkage mapping was conducted for a bivalve mollusc (Chlamys farreri) using a newly developed GBS method-2b-restriction site-associated DNA (2b-RAD). Genome survey sequencing was performed to generate a preliminary reference genome that was utilized to facilitate linkage and quantitative trait locus (QTL) mapping in C. farreri. A high-resolution linkage map was constructed with a marker density (3806) that has, to our knowledge, never been achieved in any other molluscs. The linkage map covered nearly the whole genome (99.5%) with a resolution of 0.41 cM. QTL mapping and association analysis congruously revealed two growth-related QTLs and one potential sex-determination region. An important candidate QTL gene named PROP1, which functions in the regulation of growth hormone production in vertebrates, was identified from the growth-related QTL region detected on the linkage group LG3. We demonstrate that this linkage map can serve as an important platform for improving genome assembly and unifying multiple genomic resources. Our study, therefore, exemplifies how to build up an integrative genomic framework in a non-model organism.

  4. Combining Next Generation Sequencing with Bulked Segregant Analysis to Fine Map a Stem Moisture Locus in Sorghum (Sorghum bicolor L. Moench).

    PubMed

    Han, Yucui; Lv, Peng; Hou, Shenglin; Li, Suying; Ji, Guisu; Ma, Xue; Du, Ruiheng; Liu, Guoqing

    2015-01-01

    Sorghum is one of the most promising bioenergy crops. Stem juice yield, together with stem sugar concentration, determines sugar yield in sweet sorghum. Bulked segregant analysis (BSA) is a gene mapping technique for identifying genomic regions containing genetic loci affecting a trait of interest that when combined with deep sequencing could effectively accelerate the gene mapping process. In this study, a dry stem sorghum landrace was characterized and the stem water controlling locus, qSW6, was fine mapped using QTL analysis and the combined BSA and deep sequencing technologies. Results showed that: (i) In sorghum variety Jiliang 2, stem water content was around 80% before flowering stage. It dropped to 75% during grain filling with little difference between different internodes. In landrace G21, stem water content keeps dropping after the flag leaf stage. The drop from 71% at flowering time progressed to 60% at grain filling time. Large differences exist between different internodes with the lowest (51%) at the 7th and 8th internodes at dough stage. (ii) A quantitative trait locus (QTL) controlling stem water content mapped on chromosome 6 between SSR markers Ch6-2 and gpsb069 explained about 34.7-56.9% of the phenotypic variation for the 5th to 10th internodes, respectively. (iii) BSA and deep sequencing analysis narrowed the associated region to 339 kb containing 38 putative genes. The results could help reveal molecular mechanisms underlying juice yield of sorghum and thus to improve total sugar yield.

  5. Combining Next Generation Sequencing with Bulked Segregant Analysis to Fine Map a Stem Moisture Locus in Sorghum (Sorghum bicolor L. Moench)

    PubMed Central

    Hou, Shenglin; Li, Suying; Ji, Guisu; Ma, Xue; Du, Ruiheng; Liu, Guoqing

    2015-01-01

    Sorghum is one of the most promising bioenergy crops. Stem juice yield, together with stem sugar concentration, determines sugar yield in sweet sorghum. Bulked segregant analysis (BSA) is a gene mapping technique for identifying genomic regions containing genetic loci affecting a trait of interest that when combined with deep sequencing could effectively accelerate the gene mapping process. In this study, a dry stem sorghum landrace was characterized and the stem water controlling locus, qSW6, was fine mapped using QTL analysis and the combined BSA and deep sequencing technologies. Results showed that: (i) In sorghum variety Jiliang 2, stem water content was around 80% before flowering stage. It dropped to 75% during grain filling with little difference between different internodes. In landrace G21, stem water content keeps dropping after the flag leaf stage. The drop from 71% at flowering time progressed to 60% at grain filling time. Large differences exist between different internodes with the lowest (51%) at the 7th and 8th internodes at dough stage. (ii) A quantitative trait locus (QTL) controlling stem water content mapped on chromosome 6 between SSR markers Ch6-2 and gpsb069 explained about 34.7-56.9% of the phenotypic variation for the 5th to 10th internodes, respectively. (iii) BSA and deep sequencing analysis narrowed the associated region to 339 kb containing 38 putative genes. The results could help reveal molecular mechanisms underlying juice yield of sorghum and thus to improve total sugar yield. PMID:25984727

  6. A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: high-resolution mapping and genomic structure.

    PubMed

    Cai, L; Struk, B; Adams, M D; Ji, W; Haaf, T; Kang, H L; Dho, S H; Xu, X; Ringpfeil, F; Nancarrow, J; Zäch, S; Schaen, L; Stumm, M; Niu, T; Chung, J; Lunze, K; Verrecchia, B; Goldsmith, L A; Viljoen, D; Figuera, L E; Fuchs, W; Lebwohl, M; Uitto, J; Richards, R; Hohl, D; Ramesar, R

    2000-01-01

    We have recently mapped the genetic defect underlying pseudoxanthoma elasticum (PXE), an inherited disorder characterized by progressive calcification of elastic fibers in skin, eye, and cardiovascular system, to chromosome 16p 13.1. Here we report further data on the fine-mapping and genomic structure of this locus. Haplotype analysis of informative PXE families narrowed the locus to an interval of less than 500 kb located between markers D16B9621 and D16S764. Three overlapping YAC clones were found to cover this region through YAC-STS content mapping. An overlapping BAC contig was then constructed to cover this interval and the surrounding region. About 80% of this chromosomal region has been fully sequenced using the BAC shotgun technique. Gene content and sequence analysis predicted four genes (MRP1, MRP6, PM5, and a novel transcript) and two pseudogenes (ARA and PKDI) within this interval. By screening a somatic cell hybrid panel we were able to precision-map the breakpoint of Cy185 and the starting point of a chromosomal duplication within 20 kb of BAC A962B4. The present data further refine the localization of PXE, provide additional physical cloning resources, and will aid in the eventual identification of the genetic defect causing PXE.

  7. 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.

  8. Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats

    PubMed Central

    2014-01-01

    Background Etiology of complex disorders, such as cataract and neurodegenerative diseases including age-related macular degeneration (AMD), remains poorly understood due to the paucity of animal models, fully replicating the human disease. Previously, two quantitative trait loci (QTLs) associated with early cataract, AMD-like retinopathy, and some behavioral aberrations in senescence-accelerated OXYS rats were uncovered on chromosome 1 in a cross between OXYS and WAG rats. To confirm the findings, we generated interval-specific congenic strains, WAG/OXYS-1.1 and WAG/OXYS-1.2, carrying OXYS-derived loci of chromosome 1 in the WAG strain. Both congenic strains displayed early cataract and retinopathy but differed clinically from OXYS rats. Here we applied a high-throughput RNA sequencing (RNA-Seq) strategy to facilitate nomination of the candidate genes and functional pathways that may be responsible for these differences and can contribute to the development of the senescence-accelerated phenotype of OXYS rats. Results First, the size and map position of QTL-derived congenic segments were determined by comparative analysis of coding single-nucleotide polymorphisms (SNPs), which were identified for OXYS, WAG, and congenic retinal RNAs after sequencing. The transferred locus was not what we expected in WAG/OXYS-1.1 rats. In rat retina, 15442 genes were expressed. Coherent sets of differentially expressed genes were identified when we compared RNA-Seq retinal profiles of 20-day-old WAG/OXYS-1.1, WAG/OXYS-1.2, and OXYS rats. The genes most different in the average expression level between the congenic strains included those generally associated with the Wnt, integrin, and TGF-β signaling pathways, widely involved in neurodegenerative processes. Several candidate genes (including Arhgap33, Cebpg, Gtf3c1, Snurf, Tnfaip3, Yme1l1, Cbs, Car9 and Fn1) were found to be either polymorphic in the congenic loci or differentially expressed between the strains. These genes may

  9. Genome-wide quantitative trait locus mapping identifies multiple major loci for brittle rachis and threshability in Tibetan semi-wild wheat (Triticum aestivum ssp. tibetanum Shao).

    PubMed

    Jiang, Yun-Feng; Lan, Xiu-Jin; Luo, Wei; Kong, Xing-Chen; Qi, Peng-Fei; Wang, Ji-Rui; Wei, Yu-Ming; Jiang, Qian-Tao; Liu, Ya-Xi; Peng, Yuan-Ying; Chen, Guo-Yue; Dai, Shou-Fen; Zheng, You-Liang

    2014-01-01

    Tibetan semi-wild wheat (Triticum aestivum ssp. tibetanum Shao) is a semi-wild hexaploid wheat resource that is only naturally distributed in the Qinghai-Tibet Plateau. Brittle rachis and hard threshing are two important characters of Tibetan semi-wild wheat. A whole-genome linkage map of T. aestivum ssp. tibetanum was constructed using a recombinant inbred line population (Q1028×ZM9023) with 186 lines, 564 diversity array technology markers, and 117 simple sequence repeat markers. Phenotypic data on brittle rachis and threshability, as two quantitative traits, were evaluated on the basis of the number of average spike rachis fragments per spike and percent threshability in 2012 and 2013, respectively. Quantitative trait locus (QTL) mapping performed using inclusive composite interval mapping analysis clearly identified four QTLs for brittle rachis and three QTLs for threshability. However, three loci on 2DS, 2DL, and 5AL showed pleiotropism for brittle rachis and threshability; they respectively explained 5.3%, 18.6%, and 18.6% of phenotypic variation for brittle rachis and 17.4%, 13.2%, and 35.2% of phenotypic variation for threshability. A locus on 3DS showed an independent effect on brittle rachis, which explained 38.7% of the phenotypic variation. The loci on 2DS and 3DS probably represented the effect of Tg and Br1, respectively. The locus on 5AL was in very close proximity to the Q gene, but was different from the predicted q in Tibetan semi-wild wheat. To our knowledge, the locus on 2DL has never been reported in common wheat but was prominent in T. aestivum ssp. tibetanum accession Q1028. It remarkably interacted with the locus on 5AL to affect brittle rachis. Several major loci for brittle rachis and threshability were identified in Tibetan semi-wild wheat, improving the understanding of these two characters and suggesting the occurrence of special evolution in Tibetan semi-wild wheat.

  10. Mapping and identification of a potential candidate gene for a novel maturity locus, E10, in soybean.

    PubMed

    Samanfar, Bahram; Molnar, Stephen J; Charette, Martin; Schoenrock, Andrew; Dehne, Frank; Golshani, Ashkan; Belzile, François; Cober, Elroy R

    2017-02-01

    E10 is a new maturity locus in soybean and FT4 is the predicted/potential functional gene underlying the locus. Flowering and maturity time traits play crucial roles in economic soybean production. Early maturity is critical for north and west expansion of soybean in Canada. To date, 11 genes/loci have been identified which control time to flowering and maturity; however, the molecular bases of almost half of them are not yet clear. We have identified a new maturity locus called "E10" located at the end of chromosome Gm08. The gene symbol E10e10 has been approved by the Soybean Genetics Committee. The e10e10 genotype results in 5-10 days earlier maturity than E10E10. A set of presumed E10E10 and e10e10 genotypes was used to identify contrasting SSR and SNP haplotypes. These haplotypes, and their association with maturity, were maintained through five backcross generations. A functional genomics approach using a predicted protein-protein interaction (PPI) approach (Protein-protein Interaction Prediction Engine, PIPE) was used to investigate approximately 75 genes located in the genomic region that SSR and SNP analyses identified as the location of the E10 locus. The PPI analysis identified FT4 as the most likely candidate gene underlying the E10 locus. Sequence analysis of the two FT4 alleles identified three SNPs, in the 5'UTR, 3'UTR and fourth exon in the coding region, which result in differential mRNA structures. Allele-specific markers were developed for this locus and are available for soybean breeders to efficiently develop earlier maturing cultivars using molecular marker assisted breeding.

  11. Construction of an ∼700-kb Transcript Map Around the Familial Mediterranean Fever Locus on Human Chromosome 16p13.3

    PubMed Central

    Centola, Michael; Chen, Xiaoguang; Sood, Raman; Deng, Zuoming; Aksentijevich, Ivona; Blake, Trevor; Ricke, Darrell O.; Chen, Xiang; Wood, Geryl; Zaks, Nurit; Richards, Neil; Krizman, David; Mansfield, Elizabeth; Apostolou, Sinoula; Liu, Jingmei; Shafran, Neta; Vedula, Anil; Hamon, Melanie; Cercek, Andrea; Kahan, Tanaz; Gumucio, Deborah; Callen, David F.; Richards, Robert I.; Moyzis, Robert K.; Doggett, Norman A.; Collins, Francis S.; Liu, P. Paul; Fischel-Ghodsian, Nathan; Kastner, Daniel L.

    1998-01-01

    We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequilibrium with FMF, was sequenced to completion, and the sequence annotated. A transcript map reflecting the minimal number of genes encoded within the ∼700 kb of genomic DNA surrounding the FMF locus was assembled. This map consists of 27 genes with discreet messages detectable on Northerns, in addition to three olfactory-receptor genes, a cluster of 18 tRNA genes, and two putative transcriptional units that have typical intron–exon splice junctions yet do not detect messages on Northerns. Four of the transcripts are identical to genes described previously, seven have been independently identified by the French FMF Consortium, and the others are novel. Six related zinc-finger genes, a cluster of tRNAs, and three olfactory receptors account for the majority of transcribed sequences isolated from a 315-kb FMF central region (between D16S468/D16S3070 and cosmid 377A12). Interspersed among them are several genes that may be important in inflammation. This transcript map not only has permitted the identification of the FMF gene (MEFV), but also has provided us an opportunity to probe the structural and functional features of this region of chromosome 16. PMID:9847080

  12. Homolog of the polymorphic 4q35 FSHD locus (p13E-11; D4F104S1) maps to 10qter; exclusion as a second FSHD locus in a large Danish family

    SciTech Connect

    Frants, R.R.; Bakker, E.; Vossen, R.H.A.M.

    1994-09-01

    Facioscapulohumeral muscular dystrophy (FSHD) has been mapped to 4q35 and shown to be associated with deletions that are detectable using probe p13E-11 (D4104S1). These deletions reside within highly polymorphic restriction fragments (20-300 kb) which can normally only be resolved completely using pulsed-field gel electrophoresis (PFGE). Family studies showed that p13E-11 detects two non-allelic loci, only one of which originates from 4q35 origin. In 20 CEPH families, 8 individuals were identified showing a `small` EcoRI fragment detectable by conventional Southern blotting. Linkage analysis allowed assignment of these fragments to 10qter (D10S212 and D10S180) in all families tested. Since FSHD shows genetic heterogeneity, this second p13E-11 locus on 10qter became an interesting candidate as a second FSHD family did not provide evidence for linkage on chromosome 10qter.

  13. Exploiting comparative mapping among Brassica species to accelerate the physical delimitation of a genic male-sterile locus (BnRf) in Brassica napus.

    PubMed

    Xie, Yanzhou; Dong, Faming; Hong, Dengfeng; Wan, Lili; Liu, Pingwu; Yang, Guangsheng

    2012-07-01

    The recessive genic male sterility (RGMS) line 9012AB has been used as an important pollination control system for rapeseed hybrid production in China. Here, we report our study on physical mapping of one male-sterile locus (BnRf) in 9012AB by exploiting the comparative genomics among Brassica species. The genetic maps around BnRf from previous reports were integrated and enriched with markers from the Brassica A7 chromosome. Subsequent collinearity analysis of these markers contributed to the identification of a novel ancestral karyotype block F that possibly encompasses BnRf. Fourteen insertion/deletion markers were further developed from this conserved block and genotyped in three large backcross populations, leading to the construction of high-resolution local genetic maps where the BnRf locus was restricted to a less than 0.1-cM region. Moreover, it was observed that the target region in Brassica napus shares a high collinearity relationship with a region from the Brassica rapa A7 chromosome. A BnRf-cosegregated marker (AT3G23870) was then used to screen a B. napus bacterial artificial chromosome (BAC) library. From the resulting 16 positive BAC clones, one (JBnB089D05) was identified to most possibly contain the BnRf (c) allele. With the assistance of the genome sequence from the Brassica rapa homolog, the 13.8-kb DNA fragment covering both closest flanking markers from the BAC clone was isolated. Gene annotation based on the comparison of microcollinear regions among Brassica napus, B. rapa and Arabidopsis showed that five potential open reading frames reside in this fragment. These results provide a foundation for the characterization of the BnRf locus and allow a better understanding of the chromosome evolution around BnRf.

  14. Genetic mapping of the labile (lab) gene: a recessive locus causing irregular spikelet fertility in labile-barley (Hordeum vulgare convar. labile).

    PubMed

    Youssef, Helmy M; Koppolu, Ravi; Rutten, Twan; Korzun, Viktor; Schweizer, Patrick; Schnurbusch, Thorsten

    2014-05-01

    The recessive labile locus mapped on chromosome 5HL causes irregular spikelet fertility and controls floret development as well as row-type in barley. The labile-barley displays a variable number of fertile spikelets at each rachis internode (0-3 fertile spikelets/rachis internode) which is intermediate between that observed in two- or six-rowed types. Previous re-sequencing of Vrs1 in 219 labile-barley (Hordeum vulgare L. convar. labile) accessions showed that all carried a six-rowed specific allele. We therefore hypothesized that this seemingly random reduction in spikelet fertility is most likely caused by the labile (lab) locus, which we aimed to phenotypically and genetically define. Here, we report a detailed phenotypic analysis of spikelet fertility in labile-barleys in comparison to two- and six-rowed genotypes using scanning electron microscopy analysis. We found that the first visible morphological deviation occurred during the stamen primordium stage, when we regularly observed the appearance of arrested central floral primordia in labile but not in two- or six-rowed barleys. At late stamen and early awn primordium stages, lateral florets in two-rowed and only some in labile-barley showed retarded development and reduction in size compared with fully fertile lateral florets in six-rowed barley. We used two F2 mapping populations to generate whole genome genetic linkage maps and ultimately locate the lab locus as a recessive Mendelian trait to a 4.5-5.8 cM interval at approximately 80 cM on chromosome 5HL. Our results will help identifying the role of the lab gene in relation to other spikelet fertility factors in barley.

  15. The UDP-galactose translocator gene is mapped to band Xp11. 23-p11. 22 containing the Wiskott-Aldrich Syndrome Locus

    SciTech Connect

    Hara, Takahiko; Hoshino, Masato; Aoki, Kazuhisa; Ayusawa, Dai; Kawakita, Masao ); Yamauchi, Masatake; Takahashi, Ei-ichi )

    1993-11-01

    The authors have cloned a segment of the human gene encoding UDP-galactose translocator by genetic complementation of its defective mutant in mouse FM3A cells. Chromosome mapping using fluorescent in situ hybridization revealed that the cloned gene hybridized to the Xp11.23-11.23 region of the X chromosome. This region is shared by the locus of Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency disorder, characterized by defective sugar chains on cell surface components. Genetic and phenotypic similarities suggest a possible link between UDP-galactose translocator and the Wiskott-Aldrich syndrome (WAS).

  16. Genome-Wide Single-Nucleotide Polymorphisms Discovery and High-Density Genetic Map Construction in Cauliflower Using Specific-Locus Amplified Fragment Sequencing

    PubMed Central

    Zhao, Zhenqing; Gu, Honghui; Sheng, Xiaoguang; Yu, Huifang; Wang, Jiansheng; Huang, Long; Wang, Dan

    2016-01-01

    Molecular markers and genetic maps play an important role in plant genomics and breeding studies. Cauliflower is an important and distinctive vegetable; however, very few molecular resources have been reported for this species. In this study, a novel, specific-locus amplified fragment (SLAF) sequencing strategy was employed for large-scale single nucleotide polymorphism (SNP) discovery and high-density genetic map construction in a double-haploid, segregating population of cauliflower. A total of 12.47 Gb raw data containing 77.92 M pair-end reads were obtained after processing and 6815 polymorphic SLAFs between the two parents were detected. The average sequencing depths reached 52.66-fold for the female parent and 49.35-fold for the male parent. Subsequently, these polymorphic SLAFs were used to genotype the population and further filtered based on several criteria to construct a genetic linkage map of cauliflower. Finally, 1776 high-quality SLAF markers, including 2741 SNPs, constituted the linkage map with average data integrity of 95.68%. The final map spanned a total genetic length of 890.01 cM with an average marker interval of 0.50 cM, and covered 364.9 Mb of the reference genome. The markers and genetic map developed in this study could provide an important foundation not only for comparative genomics studies within Brassica oleracea species but also for quantitative trait loci identification and molecular breeding of cauliflower. PMID:27047515

  17. Genome-Wide Single-Nucleotide Polymorphisms Discovery and High-Density Genetic Map Construction in Cauliflower Using Specific-Locus Amplified Fragment Sequencing.

    PubMed

    Zhao, Zhenqing; Gu, Honghui; Sheng, Xiaoguang; Yu, Huifang; Wang, Jiansheng; Huang, Long; Wang, Dan

    2016-01-01

    Molecular markers and genetic maps play an important role in plant genomics and breeding studies. Cauliflower is an important and distinctive vegetable; however, very few molecular resources have been reported for this species. In this study, a novel, specific-locus amplified fragment (SLAF) sequencing strategy was employed for large-scale single nucleotide polymorphism (SNP) discovery and high-density genetic map construction in a double-haploid, segregating population of cauliflower. A total of 12.47 Gb raw data containing 77.92 M pair-end reads were obtained after processing and 6815 polymorphic SLAFs between the two parents were detected. The average sequencing depths reached 52.66-fold for the female parent and 49.35-fold for the male parent. Subsequently, these polymorphic SLAFs were used to genotype the population and further filtered based on several criteria to construct a genetic linkage map of cauliflower. Finally, 1776 high-quality SLAF markers, including 2741 SNPs, constituted the linkage map with average data integrity of 95.68%. The final map spanned a total genetic length of 890.01 cM with an average marker interval of 0.50 cM, and covered 364.9 Mb of the reference genome. The markers and genetic map developed in this study could provide an important foundation not only for comparative genomics studies within Brassica oleracea species but also for quantitative trait loci identification and molecular breeding of cauliflower.

  18. Autosomal dominant postaxial polydactyly, nail dystrophy, and dental abnormalities map to chromosome 4p16, in the region containing the Ellis-van Creveld syndrome locus.

    PubMed Central

    Howard, T D; Guttmacher, A E; McKinnon, W; Sharma, M; McKusick, V A; Jabs, E W

    1997-01-01

    We have studied a four-generation family with features of Weyers acrofacial dysostosis, in which the proband has a more severe phenotype, resembling Ellis-van Creveld syndrome. Weyers acrofacial dysostosis is an autosomal dominant condition with dental anomalies, nail dystrophy, postaxial polydactyly, and mild short stature. Ellis-van Creveld syndrome is a similar condition, with autosomal recessive inheritance and the additional features of disproportionate dwarfism, thoracic dysplasia, and congenital heart disease. Linkage and haplotype analysis determined that the disease locus in this pedigree resides on chromosome 4p16, distal to the genetic marker D4S3007 and within a 17-cM region flanking the genetic locus D4S2366. This region includes the Ellis-van Creveld syndrome locus, which previously was reported to map within a 3-cM region between genetic markers D4S2957 and D4S827. Either the genes for the condition in our family and for Ellis-van Creveld syndrome are near one another or these two conditions are allelic with mutations in the same gene. These data also raise the possibility that Weyers acrofacial dysostosis is the heterozygous expression of a mutation that, in homozygous form, causes the autosomal recessive disorder Ellis-van Creveld syndrome. Images Figure 1 PMID:9399901

  19. X-linked dominant cone-rod degeneration: Linkage mapping of a new locus for retinitis pigmentosa (RP15) to Xp22.13-p22.11

    SciTech Connect

    McGuire, R.E.; Sullivan, L.S.; Daiger, S.P.

    1995-07-01

    Retinitis pigmentosa is the name given to a heterogeneous group of hereditary retinal degenerations characterized by progressive visual field loss, pigmentary changes of the retina, abnormal electroretinograms, and, frequently, night blindness. In this study, we investigated a family with dominant cone-rod degeneration, a variant form of retinitis pigmentosa. We used microsatellite markers to test for linkage to the disease locus and exluded all mapped autosomal loci. However, a marker from the short arm of the X chromosome, DXS989, showed 0% recombination to the disease locus, with a maximum lod (log-odds) score of 3.3. On the basis of this marker, the odds favoring X-linked dominant versus autosomal dominant inheritance are > 10{sup 5}:1. Haplotype analysis using an additional nine microsatellite markers places the disease locus in the Xp22.13-p22.11 region and excludes other X-linked disease loci causing retinal degeneration. The clinical expression of the retinal degeneration is consistent with X-linked dominant inheritance with milder, variable effects of Lyonization affecting expression in females. On the basis of these data we propose that this family has a novel form of dominant, X-linked cone-rod degeneration with the gene symbol {open_quotes}RP15{close_quotes}. 17 refs., 2 figs., 4 tabs.

  20. Genetic Map-Based Location of the Red Clover (Trifolium pratense L.) Gametophytic Self-incompatibility Locus

    USDA-ARS?s Scientific Manuscript database

    Red clover is a hermaphadidic allogamous diploid (2n = 2x = 14) with a homomorphic gametophytic self-incompatibility (GSI) system red clover (Trifolium pratense L.). Red clover GSI has long been studied and it is thought that the genetic control of GSI constitutes a single locus. Although GSI gene...

  1. Construction of a high-density genetic map and the X/Y sex-determining gene mapping in spinach based on large-scale markers developed by specific-locus amplified fragment sequencing (SLAF-seq).

    PubMed

    Qian, Wei; Fan, Guiyan; Liu, Dandan; Zhang, Helong; Wang, Xiaowu; Wu, Jian; Xu, Zhaosheng

    2017-04-04

    Cultivated spinach (Spinacia oleracea L.) is one of the most widely cultivated types of leafy vegetable in the world, and it has a high nutritional value. Spinach is also an ideal plant for investigating the mechanism of sex determination because it is a dioecious species with separate male and female plants. Some reports on the sex labeling and localization of spinach in the study of molecular markers have surfaced. However, there have only been two reports completed on the genetic map of spinach. The lack of rich and reliable molecular markers and the shortage of high-density linkage maps are important constraints in spinach research work. In this study, a high-density genetic map of spinach based on the Specific-locus Amplified Fragment Sequencing (SLAF-seq) technique was constructed; the sex-determining gene was also finely mapped. Through bio-information analysis, 50.75 Gb of data in total was obtained, including 207.58 million paired-end reads. Finally, 145,456 high-quality SLAF markers were obtained, with 27,800 polymorphic markers and 4080 SLAF markers were finally mapped onto the genetic map after linkage analysis. The map spanned 1,125.97 cM with an average distance of 0.31 cM between the adjacent marker loci. It was divided into 6 linkage groups corresponding to the number of spinach chromosomes. Besides, the combination of Bulked Segregation Analysis (BSA) with SLAF-seq technology(super-BSA) was employed to generate the linkage markers with the sex-determining gene. Combined with the high-density genetic map of spinach, the sex-determining gene X/Y was located at the position of the linkage group (LG) 4 (66.98 cM-69.72 cM and 75.48 cM-92.96 cM), which may be the ideal region for the sex-determining gene. A high-density genetic map of spinach based on the SLAF-seq technique was constructed with a backcross (BC1) population (which is the highest density genetic map of spinach reported at present). At the same time, the sex-determining gene X/Y was mapped

  2. 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.

  3. Genome-wide Scan and Fine-Mapping Linkage Study of Androgenetic Alopecia Reveals a Locus on Chromosome 3q26

    PubMed Central

    Hillmer, Axel M.; Flaquer, Antonia; Hanneken, Sandra; Eigelshoven, Sibylle; Kortüm, Anne-Katrin; Brockschmidt, Felix F.; Golla, Astrid; Metzen, Christine; Thiele, Holger; Kolberg, Susanne; Reinartz, Roman; Betz, Regina C.; Ruzicka, Thomas; Hennies, Hans Christian; Kruse, Roland; Nöthen, Markus M.

    2008-01-01

    Androgenetic alopecia (AGA, male pattern baldness) is the most common form of hair loss. The origin of AGA is genetic, with the X chromosome located androgen receptor gene (AR) being the only risk gene identified to date. We present the results of a genome-wide linkage study of 95 families and linkage fine mapping of the 3q21-q29, 11q14-q25, 18p11-q23, and 19p13-q13 regions in an extended sample of 125 families of German descent. The locus with strongest evidence for linkage was mapped to 3q26 with a nonparametric linkage (NPL) score of 3.97 (empirical p value = 0.00055). This is the first step toward the identification of new susceptibility genes in AGA, a process which will provide important insights into the molecular and cellular basis of scalp hair loss. PMID:18304493

  4. Mapping-by-Sequencing Identifies HvPHYTOCHROME C as a Candidate Gene for the early maturity 5 Locus Modulating the Circadian Clock and Photoperiodic Flowering in Barley

    PubMed Central

    Pankin, Artem; Campoli, Chiara; Dong, Xue; Kilian, Benjamin; Sharma, Rajiv; Himmelbach, Axel; Saini, Reena; Davis, Seth J; Stein, Nils; Schneeberger, Korbinian; von Korff, Maria

    2014-01-01

    Phytochromes play an important role in light signaling and photoperiodic control of flowering time in plants. Here we propose that the red/far-red light photoreceptor HvPHYTOCHROME C (HvPHYC), carrying a mutation in a conserved region of the GAF domain, is a candidate underlying the early maturity 5 locus in barley (Hordeum vulgare L.). We fine mapped the gene using a mapping-by-sequencing approach applied on the whole-exome capture data from bulked early flowering segregants derived from a backcross of the Bowman(eam5) introgression line. We demonstrate that eam5 disrupts circadian expression of clock genes. Moreover, it interacts with the major photoperiod response gene Ppd-H1 to accelerate flowering under noninductive short days. Our results suggest that HvPHYC participates in transmission of light signals to the circadian clock and thus modulates light-dependent processes such as photoperiodic regulation of flowering. PMID:24996910

  5. Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes.

    PubMed

    Cortes, Adrian; Field, Judith; Glazov, Evgeny A; Hadler, Johanna; Stankovich, Jim; Brown, Matthew A

    2013-06-01

    Multiple sclerosis (MS) is a common chronic inflammatory disease of the central nervous system. Susceptibility to the disease is affected by both environmental and genetic factors. Genetic factors include haplotypes in the histocompatibility complex (MHC) and over 50 non-MHC loci reported by genome-wide association studies. Amongst these, we previously reported polymorphisms in chromosome 12q13-14 with a protective effect in individuals of European descent. This locus spans 288 kb and contains 17 genes, including several candidate genes which have potentially significant pathogenic and therapeutic implications. In this study, we aimed to fine-map this locus. We have implemented a two-phase study: a variant discovery phase where we have used next-generation sequencing and two target-enrichment strategies [long-range polymerase chain reaction (PCR) and Nimblegen's solution phase hybridization capture] in pools of 25 samples; and a genotyping phase where we genotyped 712 variants in 3577 healthy controls and 3269 MS patients. This study confirmed the association (rs2069502, P = 9.9 × 10(-11), OR = 0.787) and narrowed down the locus of association to an 86.5 kb region. Although the study was unable to pinpoint the key-associated variant, we have identified a 42 (genotyped and imputed) single-nucleotide polymorphism haplotype block likely to harbour the causal variant. No evidence of association at previously reported low-frequency variants in CYP27B1 was observed. As part of the study we compared variant discovery performance using two target-enrichment strategies. We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.

  6. VNTR internal structure mapping at the {alpha}-globin 3{prime}HVR locus reveals a hierachy of related lineages in oceania

    SciTech Connect

    Martinson, J.J.; Clegg, J.B.; Boyce, A.J.

    1994-09-01

    Analysis of the {alpha}-globin gene complex in Oceania has revealed many different rearrangements which remove one of the adult globin genes. Frequencies of these deletion chromosomes are elevated by malarial resistance conferred by the resulting {alpha}-thalassaemia. One particular deletion chromosome, designated -{alpha}{sup 3.7}III, is found at high levels in Melanesia and Polynesia: RFLP haplotype analysis shows that this deletion is always found on chromosomes bearing the IIIa haplotype and is likely to be the product of one single rearrangement event. A subset of the -{alpha}{sup 3.7}III chromosomes carries a more recent mutation which generates the haemoglobin variant HbJ{sup Tongariki}. We have characterized the allelic variation at the 3{prime}HVR VNTR locus located 6 kb from the globin genes in each of these groups of chromosomes. We have determined the internal structure of these alleles by RFLP mapping of PCR-amplified DNA: within each group, the allelic diversity results from the insertion and/or deletion of small {open_quotes}motifs{close_quotes} of up to 6 adjacent repeats. Mapping of 3{prime}HVR alleles associated with other haplotypes reveals that these are composed of repeat arrays that are substantially different to those derived from IIIa chromosomes, indicating that interchromosomal recombination between heterologous haplotypes does not account for any of the diversity seen to date. We have recently shown that allelic size variation at the two VNTR loci flanking the {alpha}-globin complex is very closely linked to the haplotypes known to be present at this locus. Here we show that, within a haplotype, VNTR alleles are very closely related to each other on the basis of internal structure and demonstrate that intrachromosomal mutation processes involving small numbers of tandem repeats are the main cause of variation at this locus.

  7. 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.

  8. Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart studies.

    PubMed

    Nalls, Michael A; Wilson, James G; Patterson, Nick J; Tandon, Arti; Zmuda, Joseph M; Huntsman, Scott; Garcia, Melissa; Hu, Donglei; Li, Rongling; Beamer, Brock A; Patel, Kushang V; Akylbekova, Ermeg L; Files, Joe C; Hardy, Cheryl L; Buxbaum, Sarah G; Taylor, Herman A; Reich, David; Harris, Tamara B; Ziv, Elad

    2008-01-01

    White blood cell count (WBC) is an important clinical marker that varies among different ethnic groups. African Americans are known to have a lower WBC than European Americans. We surveyed the entire genome for loci underlying this difference in WBC by using admixture mapping. We analyzed data from African American participants in the Health, Aging, and Body Composition Study and the Jackson Heart Study. Participants of both studies were genotyped across >or= 1322 single nucleotide polymorphisms that were pre-selected to be informative for African versus European ancestry and span the entire genome. We used these markers to estimate genetic ancestry in each chromosomal region and then tested the association between WBC and genetic ancestry at each locus. We found a locus on chromosome 1q strongly associated with WBC (p < 10(-12)). The strongest association was with a marker known to affect the expression of the Duffy blood group antigen. Participants who had both copies of the common West African allele had a mean WBC of 4.9 (SD 1.3); participants who had both common European alleles had a mean WBC of 7.1 (SD 1.3). This variant explained approximately 20% of population variation in WBC. We used admixture mapping, a novel method for conducting genetic-association studies, to find a region that was significantly associated with WBC on chromosome 1q. Additional studies are needed to determine the biological mechanism for this effect and its clinical implications.

  9. Murine phosphatidylserine-specific phospholipase A1 (Ps-pla1) maps to chromosome 16 but is distinct from the lpd (lipid defect) locus.

    PubMed

    Wen, X Y; Stewart, A K; Skaug, J; Wei, E; Tsui, L C

    2001-02-01

    We have previously generated a mouse transgenic line with an insertional mutation designated lpd that demonstrates a phenotype of hypertriglyceridemia and fatty liver. Since the recently identified phosphatidylserine-specific phospholipase A1 (PS-PLA1) demonstrates significant homology to triglyceride lipases, we reasoned that the mouse Ps-plaI gene may be the disrupted gene within the lpd locus. Using a rat PS-PLA1 cDNA sequence to search the EST database, we identified a mouse EST homolog AA839424. Sequencing analysis of AA839424 revealed a putative Ps-pla1 protein of 456 amino acids with extensive overall structural conservation with human and rat PS-PLA1 and with triglyceride lipases. Conserved sequences in Ps-pla1 include a lipase consensus sequences GxSxG, a catalytic triad, and eight of the ten conserved cysteine residues that are required for tertiary structure. Mouse Ps-plal carries a phosphatidylserine-binding motif that is absent in all triglyceride lipases. Using a mouse whole-genome radiation hybrid (WG-RH) mapping panel (T31), we mapped mouse Ps-pla1 to Chromosome (Chr) 16 between genetic markers D16Mit194 and D16Mit38, which is 17.1 cM centromeric to the lpd locus. On the basis of chromosome location, we conclude that Ps-pla1 and lpd are distinct genes in lipid metabolism.

  10. Mapping of jog locus to the region between D6Mit104 and D6Mit336 on mouse chromosome 6.

    PubMed

    Sun, Xiao-yang; Chen, Zi-yan; Kanou, Yasuhiko; Takagishi, Yoshiko; Hayashi, Yoshitaka; Ohno, Tamio; Murata, Yoshiharu; Oda, Sen-ichi

    2007-10-01

    The joggle mouse is a recessive ataxic mutant carrying an unknown mutation in a C3H/He (C3H)-derived chromosomal segment. Taking advantage of the mouse genome database, we selected 127 DNA microsatellite markers showing heterozygosity between C3H and C57BL/6J (B6) and a first round of screening for the joggle mutation was performed on B6-jog/+ partial congenic mice (N4). We identified 4 chromosomal regions in which 13 microsatellite markers show heterozygosity between C3H and B6. Then, we analyzed the genotype of these 4 chromosomal regions in mice that showed the joggle phenotype and mapped the jog locus between markers D6Mit104 (111.4 Mb) and D6Mit336 (125.1 Mb) (an interval of 13.7 Mb) on chromosome 6. By using a partial congenic strain together with the mouse genome database, we successfully mapped the chromosomal localization of the jog locus much more efficiently than by conventional linkage analysis.

  11. Design and analysis of genetic association studies to finely map a locus identified by linkage analysis: sample size and power calculations.

    PubMed

    Hanson, R L; Looker, H C; Ma, L; Muller, Y L; Baier, L J; Knowler, W C

    2006-05-01

    Association (e.g. case-control) studies are often used to finely map loci identified by linkage analysis. We investigated the influence of various parameters on power and sample size requirements for such a study. Calculations were performed for various values of a high-risk functional allele (fA), frequency of a marker allele associated with the high risk allele (f1), degree of linkage disquilibrium between functional and marker alleles (D') and trait heritability attributable to the functional locus (h2). The calculations show that if cases and controls are selected from equal but opposite extreme quantiles of a quantitative trait, the primary determinants of power are h2 and the specific quantiles selected. For a dichotomous trait, power also depends on population prevalence. Power is optimal if functional alleles are studied (fA= f1 and D'= 1.0) and can decrease substantially as D' diverges from 1.0 or as f(1) diverges from fA. These analyses suggest that association studies to finely map loci are most powerful if potential functional polymorphisms are identified a priori or if markers are typed to maximize haplotypic diversity. In the absence of such information, expected minimum power at a given location for a given sample size can be calculated by specifying a range of potential frequencies for fA (e.g. 0.1-0.9) and determining power for all markers within the region with specification of the expected D' between the markers and the functional locus. This method is illustrated for a fine-mapping project with 662 single nucleotide polymorphisms in 24 Mb. Regions differed by marker density and allele frequencies. Thus, in some, power was near its theoretical maximum and little additional information is expected from additional markers, while in others, additional markers appear to be necessary. These methods may be useful in the analysis and interpretation of fine-mapping studies.

  12. High-resolution genetic linkage mapping, high-temperature tolerance and growth-related quantitative trait locus (QTL) identification in Marsupenaeus japonicus.

    PubMed

    Lu, Xia; Luan, Sheng; Hu, Long Yang; Mao, Yong; Tao, Ye; Zhong, Sheng Ping; Kong, Jie

    2016-06-01

    The Kuruma prawn, Marsupenaeus japonicus, is one of the most promising marine invertebrates in the industry in Asia, Europe and Australia. However, the increasing global temperatures result in considerable economic losses in M. japonicus farming. In the present study, to select genetically improved animals for the sustainable development of the Kuruma prawn industry, a high-resolution genetic linkage map and quantitative trait locus (QTL) identification were performed using the RAD technology. The maternal map contained 5849 SNP markers and spanned 3127.23 cM, with an average marker interval of 0.535 cM. Instead, the paternal map contained 3927 SNP markers and spanned 3326.19 cM, with an average marker interval of 0.847 cM. The consensus map contained 9289 SNP markers and spanned 3610.90 cM, with an average marker interval of 0.388 cM and coverage of 99.06 % of the genome. The markers were grouped into 41 linkage groups in the maps. Significantly, negative correlation was detected between high-temperature tolerance (UTT) and body weight (BW). The QTL mapping revealed 129 significant QTL loci for UTT and four significant QTL loci for BW at the genome-wide significance threshold. Among these QTLs, 129 overlapped with linked SNPs, and the remaining four were located in regions between contiguous SNPs. They explained the total phenotypic variance ranging from 8.9 to 12.4 %. Because of a significantly negative correlation between growth and high-temperature tolerance, we demonstrate that this high-resolution linkage map and QTLs would be useful for further marker-assisted selection in the genetic improvement of M. japonicus.

  13. Saturated genic SNP mapping identified functional candidates and selection tools for the Pinus monticola Cr2 locus controlling resistance to white pine blister rust.

    PubMed

    Liu, Jun-Jun; Sniezko, Richard A; Zamany, Arezoo; Williams, Holly; Wang, Ning; Kegley, Angelia; Savin, Douglas P; Chen, Hao; Sturrock, Rona N

    2017-09-01

    Molecular breeding incorporates efficient tools to increase rust resistance in five-needle pines. Susceptibility of native five-needle pines to white pine blister rust (WPBR), caused by the non-native invasive fungus Cronartium ribicola (J.C. Fisch.), has significantly reduced wild populations of these conifers in North America. Major resistance (R) genes against specific avirulent pathotypes have been found in several five-needle pine species. In this study, we screened genic SNP markers by comparative transcriptome and genetic association analyses and constructed saturated linkage maps for the western white pine (Pinus monticola) R locus (Cr2). Phenotypic segregation was measured by a hypersensitive reaction (HR)-like response on the needles and disease symptoms of cankered stems post inoculation by the C. ribicola avcr2 race. SNP genotypes were determined by HRM- and TaqMan-based SNP genotyping. Saturated maps of the Cr2-linkage group (LG) were constructed in three seed families using a total of 34 SNP markers within 21 unique genes. Cr2 was consistently flanked by contig_2142 (encoding a ruvb-like protein) and contig_3772 (encoding a delta-fatty acid desaturase) across the three seed families. Cr2 was anchored to the Pinus consensus LG-1, which differs from LGs where other R loci of Pinus species were mapped. GO annotation identified a set of NBS-LRR and other resistance-related genes as R candidates in the Cr2 region. Association of one nonsynonymous SNP locus of an NBS-LRR gene with Cr2-mediated phenotypes provides a valuable tool for marker-assisted selection (MAS), which will shorten the breeding cycle of resistance screening and aid in the restoration of WPBR-disturbed forest ecosystems. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  14. High-Resolution Fine Mapping and Fluorescence in Situ Hybridization Analysis of sun, a Locus Controlling Tomato Fruit Shape, Reveals a Region of the Tomato Genome Prone to DNA Rearrangements

    PubMed Central

    van der Knaap, E.; Sanyal, A.; Jackson, S. A.; Tanksley, S. D.

    2004-01-01

    The locus sun on the short arm of tomato chromosome 7 controls morphology of the fruit. Alleles from wild relatives impart a round shape, while alleles from certain cultivated varieties impart an oval shape typical of roma-type tomatoes. We fine mapped the locus in two populations and investigated the genome organization of the region spanning and flanking sun. The first high-resolution genetic map of the sun locus was constructed using a nearly isogenic F2 population derived from a cross between Lycopersicon pennellii introgression line IL7-4 and L. esculentum cv Sun1642. The mapping combined with results from pachytene FISH experiments demonstrated that the top of chromosome 7 is inverted in L. pennellii accession LA716. sun was located close to the chromosomal breakpoint and within the inversion, thereby precluding map-based cloning of the gene using this population. The fruit-shape locus was subsequently fine mapped in a population derived from a cross between L. esculentum Sun1642 and L. pimpinellifolium LA1589. Chromosome walking using clones identified from several large genomic insert libraries resulted in two noncontiguous contigs flanking sun. Fiber-FISH analysis showed that distance between the two contigs measured 68 kb in L. esculentum Sun1642 and 38 kb in L. pimpinellifolium LA1589, respectively. The sun locus mapped between the two contigs, suggesting that allelic variation at this locus may be due to an insertion/deletion event. The results demonstrate that sun is located in a highly dynamic region of the tomato genome. PMID:15611181

  15. Development of a 10,000 Locus Genetic Map of the Sunflower Genome Based on Multiple Crosses

    PubMed Central

    Bowers, John E.; Bachlava, Eleni; Brunick, Robert L.; Rieseberg, Loren H.; Knapp, Steven J.; Burke, John M.

    2012-01-01

    Genetic linkage maps have the potential to facilitate the genetic dissection of complex traits and comparative analyses of genome structure, as well as molecular breeding efforts in species of agronomic importance. Until recently, the majority of such maps was based on relatively low-throughput marker technologies, which limited marker density across the genome. The availability of high-throughput genotyping technologies has, however, made possible the efficient development of high-density genetic maps. Here, we describe the analysis and integration of genotypic data from four sunflower (Helianthus annuus L.) mapping populations to produce a consensus linkage map of the sunflower genome. Although the individual maps (which contained 3500–5500 loci each) were highly colinear, we observed localized variation in recombination rates in several genomic regions. We also observed several gaps up to 26 cM in length that completely lacked mappable markers in individual crosses, presumably due to regions of identity by descent in the mapping parents. Because these regions differed by cross, the consensus map of 10,080 loci contained no such gaps, clearly illustrating the value of simultaneously analyzing multiple mapping populations. PMID:22870395

  16. Development of a 10,000 locus genetic map of the sunflower genome based on multiple crosses.

    PubMed

    Bowers, John E; Bachlava, Eleni; Brunick, Robert L; Rieseberg, Loren H; Knapp, Steven J; Burke, John M

    2012-07-01

    Genetic linkage maps have the potential to facilitate the genetic dissection of complex traits and comparative analyses of genome structure, as well as molecular breeding efforts in species of agronomic importance. Until recently, the majority of such maps was based on relatively low-throughput marker technologies, which limited marker density across the genome. The availability of high-throughput genotyping technologies has, however, made possible the efficient development of high-density genetic maps. Here, we describe the analysis and integration of genotypic data from four sunflower (Helianthus annuus L.) mapping populations to produce a consensus linkage map of the sunflower genome. Although the individual maps (which contained 3500-5500 loci each) were highly colinear, we observed localized variation in recombination rates in several genomic regions. We also observed several gaps up to 26 cM in length that completely lacked mappable markers in individual crosses, presumably due to regions of identity by descent in the mapping parents. Because these regions differed by cross, the consensus map of 10,080 loci contained no such gaps, clearly illustrating the value of simultaneously analyzing multiple mapping populations.

  17. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25.

    PubMed

    Hung, Rayjean J; McKay, James D; Gaborieau, Valerie; Boffetta, Paolo; Hashibe, Mia; Zaridze, David; Mukeria, Anush; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Chen, Chu; Goodman, Gary; Field, John K; Liloglou, Triantafillos; Xinarianos, George; Cassidy, Adrian; McLaughlin, John; Liu, Geoffrey; Narod, Steven; Krokan, Hans E; Skorpen, Frank; Elvestad, Maiken Bratt; Hveem, Kristian; Vatten, Lars; Linseisen, Jakob; Clavel-Chapelon, Françoise; Vineis, Paolo; Bueno-de-Mesquita, H Bas; Lund, Eiliv; Martinez, Carmen; Bingham, Sheila; Rasmuson, Torgny; Hainaut, Pierre; Riboli, Elio; Ahrens, Wolfgang; Benhamou, Simone; Lagiou, Pagona; Trichopoulos, Dimitrios; Holcátová, Ivana; Merletti, Franco; Kjaerheim, Kristina; Agudo, Antonio; Macfarlane, Gary; Talamini, Renato; Simonato, Lorenzo; Lowry, Ray; Conway, David I; Znaor, Ariana; Healy, Claire; Zelenika, Diana; Boland, Anne; Delepine, Marc; Foglio, Mario; Lechner, Doris; Matsuda, Fumihiko; Blanche, Helene; Gut, Ivo; Heath, Simon; Lathrop, Mark; Brennan, Paul

    2008-04-03

    Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.

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

    SciTech Connect

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

    1994-09-01

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

  19. Characterization and mapping of LanrBo: a locus conferring anthracnose resistance in narrow-leafed lupin (Lupinus angustifolius L.).

    PubMed

    Fischer, Kristin; Dieterich, Regine; Nelson, Matthew N; Kamphuis, Lars G; Singh, Karam B; Rotter, Björn; Krezdorn, Nicolas; Winter, Peter; Wehling, Peter; Ruge-Wehling, Brigitte

    2015-10-01

    A novel and highly effective source of anthracnose resistance in narrow-leafed lupin was identified. Resistance was shown to be governed by a single dominant locus. Molecular markers have been developed, which can be used for selecting resistant genotypes in lupin breeding. A screening for anthracnose resistance of a set of plant genetic resources of narrow-leafed lupin (Lupinus angustifolius L.) identified the breeding line Bo7212 as being highly resistant to anthracnose (Colletotrichum lupini). Segregation analysis indicated that the resistance of Bo7212 is inherited by a single dominant locus. The corresponding resistance gene was given the designation LanrBo. Previously published molecular anchor markers allowed us to locate LanrBo on linkage group NLL-11 of narrow-leafed lupin. Using information from RNAseq data obtained with inoculated resistant vs. susceptible lupin entries as well as EST-sequence information from the model genome Lotus japonicus, additional SNP and EST markers linked to LanrBo were derived. A bracket of two LanrBo-flanking markers allows for precise marker-assisted selection of the novel resistance gene in narrow-leafed lupin breeding programs.

  20. Human pedigree-based quantitative-trait-locus mapping: localization of two genes influencing HDL-cholesterol metabolism.

    PubMed Central

    Almasy, L; Hixson, J E; Rainwater, D L; Cole, S; Williams, J T; Mahaney, M C; VandeBerg, J L; Stern, M P; MacCluer, J W; Blangero, J

    1999-01-01

    Common disorders with genetic susceptibilities involve the action of multiple genes interacting with each other and with environmental factors, making it difficult to localize the specific genetic loci responsible. An important route to the disentangling of this complex inheritance is through the study of normal physiological variation in quantitative risk factors that may underlie liability to disease. We present an analysis of HDL-cholesterol (HDL-C), which is inversely correlated with risk of heart disease. A variety of HDL subphenotypes were analyzed, including HDL particle-size classes and the concentrations and proportions of esterified and unesterified HDL-C. Results of a complete genomic screen in large, randomly ascertained pedigrees implicated two loci, one on chromosome 8 and the other on chromosome 15, that influence a component of HDL-C-namely, unesterified HDL2a-C. Multivariate analyses of multiple HDL phenotypes and simultaneous multilocus analysis of the quantitative-trait loci identified permit further characterization of the genetic effects on HDL-C. These analyses suggest that the action of the chromosome 8 locus is specific to unesterified cholesterol levels, whereas the chromosome 15 locus appears to influence both HDL-C concentration and distribution of cholesterol among HDL particle sizes. PMID:10330356

  1. Interferon-induced guanylate-binding proteins: mapping of the murine Gbp-1 locus to chromosome 3.

    PubMed

    Prochazka, M; Staeheli, P; Holmes, R S; Haller, O

    1985-09-01

    GBP-1 is the predominant species of a family of guanylate-binding proteins synthesized in mouse cells in response to interferons (IFNs) alpha, beta, or gamma. IFN inducibility of this 65,000-Da protein is controlled by alleles at a single autosomal locus, Gbp-1, with allele a encoding inducibility and allele b noninducibility. Here, we present evidence suggesting that both alleles occur in outbred populations of wild mice. Using recombinant inbred strains and classical linkage analysis of offspring of two-point and three-point backcrosses we demonstrate that Gbp-1 is linked to Adh-3 (encoding alcohol dehydrogenase C2) and VaJ (varitintwaddler-Jackson) located on the distal part of chromosome 3. The relevant recombination frequencies (RFs) (+/- SE) were 3.5 (+/- 1.1) and 11.7 (+/- 2.8)%, respectively. We further show that strain B6.C-H-23c/By(HW 53), congenic for a small segment of chromosome 3, carries the BALB/c alleles at both the Gbp-1 and the Adh-3 locus and not the alleles of the B6 background strain confirming the chromosomal location and close linkage of the two loci.

  2. Toward cloning of a novel ataxia gene: Refined assignment and physical map of the IOSCA locus (SCA8) on 10q24

    SciTech Connect

    Nikali, K.; Isosomppi, J.; Suomalainen, A.

    1997-01-15

    Infantile onset spinocerebellar ataxia (IOSCA) is a progressive neurological disorder of unknown etiology. It is inherited as an autosomal recessive trait and has so far been reported in just 19 Finnish patients in 13 separate families. We have previously assigned the IOSCA locus (HGMW-approved symbol SCA8) to chromosome 10q, where no previously identified ataxia loci are located. Haplotype analysis combined with genealogical data provided evidence that all the IOSCA cases in Finland originate from a single 30- to 40-generation-old founder mutation. By analyzing extended disease haplotypes observed today, the IOSCA locus can now be restricted to a region between two adjacent microsatellites, D10S192 and D10S1265, with no genetic intermarker distance. We have constructed a detailed physical map of this 270-kb IOSCA region and cytogenetically localized it to 10q24. We have also assigned two previously known genes, PAX2 and CYP17, more precisely into this region, but the sequence analysis of coding regions of these two genes has not revealed mutations in an IOSCA patient. The obtained long-range clones will form the basis for the isolation of a novel ataxia gene. 42 refs., 3 figs.

  3. In Southern Africa, Brown Oculocutaneous Albinism (BOCA) Maps to the OCA2 Locus on Chromosome 15q: P-Gene Mutations Identified

    PubMed Central

    Manga, Prashiela; Kromberg, Jennifer G. R.; Turner, Angela; Jenkins, Trefor; Ramsay, Michele

    2001-01-01

    In southern Africa, brown oculocutaneous albinism (BOCA) is a distinct pigmentation phenotype. In at least two cases, it has occurred in the same families as tyrosinase-positive oculocutaneous albinism (OCA2), suggesting that it may be allelic, despite the fact that this phenotype was attributed to mutations in the TYRP1 gene in an American individual of mixed ancestry. Linkage analysis in five families mapped the BOCA locus to the same region as the OCA2 locus (maximum LOD 3.07; θ=0 using a six-marker haplotype). Mutation analysis of the human homologue of the mouse pink-eyed dilution gene (P), in 10 unrelated individuals with BOCA revealed that 9 had one copy of the 2.7-kb deletion. No other mutations were identified. Additional haplotype studies, based on closely linked markers (telomere to centromere: D15S1048, D15S1019, D15S1533, P-gene 2.7-kb deletion, D15S219, and D15S156) revealed several BOCA-associated P haplotypes. These could be divided into two core haplotypes, suggesting that a limited number of P-gene mutations give rise to this phenotype. PMID:11179026

  4. Identification and mapping of a novel blackleg resistance locus LepR4 in the progenies from Brassica napus × B. rapa subsp. sylvestris.

    PubMed

    Yu, Fengqun; Gugel, Richard K; Kutcher, H Randy; Peng, Gary; Rimmer, S Roger

    2013-02-01

    Blackleg, caused by Leptosphaeria maculans, is one of the most economically important diseases of Brassica napus worldwide. Two blackleg-resistant lines, 16S and 61446, were developed through interspecific hybridization between B. napus and B. rapa subsp. sylvestris and backcrossing to B. napus. Classical genetic analysis demonstrated that a single recessive gene in both lines conferred resistance to L. maculans and that the resistance alleles were allelic. Using BC(1) progeny derived from each resistant plant, this locus was mapped to B. napus linkage group N6 and was flanked by microsatellite markers sN2189b and sORH72a in an interval of about 10 cM, in a region equivalent to about 6 Mb of B. rapa DNA sequence. This new resistance gene locus was designated as LepR4. The two lines were evaluated for resistance to a wide range of L. maculans isolates using cotyledon inoculation tests under controlled environment conditions, and for stem canker resistance in blackleg field nurseries. Results indicated that line 16S, carrying LepR4a, was highly resistant to all isolates tested on cotyledons and had a high level of stem canker resistance under field conditions. Line 61446, carrying LepR4b, was only resistant to some of the isolates tested on cotyledons and was weakly resistant to stem canker under field conditions.

  5. Genetic mapping identifies a major locus spanning P450 clusters associated with pyrethroid resistance in kdr-free Anopheles arabiensis from Chad.

    PubMed

    Witzig, C; Parry, M; Morgan, J C; Irving, H; Steven, A; Cuamba, N; Kerah-Hinzoumbé, C; Ranson, H; Wondji, C S

    2013-04-01

    Prevention of malaria transmission throughout much of Africa is dependent on bednets that are impregnated with pyrethroid insecticides. Anopheles arabiensis is the major malaria vector in Chad and efforts to control this vector are threatened by the emergence of pyrethroid resistance. WHO bioassays revealed that An. arabiensis from Ndjamena is resistant to pyrethroids and dichlorodiphenyltrichloroethane (DDT) but fully susceptible to carbamates and organophosphates. No 1014F or 1014S kdr alleles were detected in this population. To determine the mechanisms that are responsible for resistance, genetic crosses were established between the Ndja strain and an insecticide susceptible population from Mozambique. Resistance was inherited as an autosomal trait and quantitative trait locus (QTL) mapping identified a single major locus on chromosome 2R, which explained 24.4% of the variance in resistance. This QTL is enriched in P450 genes including 25 cytochrome P450s in total. One of these, Cyp6p4 is 22-fold upregulated in the Ndja strain compared with the susceptible. Piperonyl butoxide (PBO) synergist and biochemical assays further support a role for P450s in conferring pyrethroid resistance in this population.

  6. Mapping small-effect and linked quantitative trait loci for complex traits in backcross or DH populations via a multi-locus GWAS methodology

    PubMed Central

    Wang, Shi-Bo; Wen, Yang-Jun; Ren, Wen-Long; Ni, Yuan-Li; Zhang, Jin; Feng, Jian-Ying; Zhang, Yuan-Ming

    2016-01-01

    Composite interval mapping (CIM) is the most widely-used method in linkage analysis. Its main feature is the ability to control genomic background effects via inclusion of co-factors in its genetic model. However, the result often depends on how the co-factors are selected, especially for small-effect and linked quantitative trait loci (QTL). To address this issue, here we proposed a new method under the framework of genome-wide association studies (GWAS). First, a single-locus random-SNP-effect mixed linear model method for GWAS was used to scan each putative QTL on the genome in backcross or doubled haploid populations. Here, controlling background via selecting markers in the CIM was replaced by estimating polygenic variance. Then, all the peaks in the negative logarithm P-value curve were selected as the positions of multiple putative QTL to be included in a multi-locus genetic model, and true QTL were automatically identified by empirical Bayes. This called genome-wide CIM (GCIM). A series of simulated and real datasets was used to validate the new method. As a result, the new method had higher power in QTL detection, greater accuracy in QTL effect estimation, and stronger robustness under various backgrounds as compared with the CIM and empirical Bayes methods. PMID:27435756

  7. A reference genetic map of Muscadinia rotundifolia and identification of Ren5, a new major locus for resistance to grapevine powdery mildew.

    PubMed

    Blanc, Sophie; Wiedemann-Merdinoglu, Sabine; Dumas, Vincent; Mestre, Pere; Merdinoglu, Didier

    2012-12-01

    Muscadinia rotundifolia, a species closely related to cultivated grapevine Vitis vinifera, is a major source of resistance to grapevine downy and powdery mildew, two major threats to cultivated traditional cultivars of V. vinifera respectively caused by the oomycete Plasmopara viticola and the ascomycete Erisyphe necator. The aim of the present work was to develop a reference genetic linkage map based on simple sequence repeat (SSR) markers for M. rotundifolia. This map was created using S1 M. rotundifolia cv. Regale progeny, and covers 948 cM on 20 linkage groups, which corresponds to the expected chromosome number for muscadine. The comparison of the genetic maps of V. vinifera and M. rotundifolia revealed a high macrosynteny between the genomes of both species. The S1 progeny was used to assess the general level of resistance of M. rotundifolia to P. viticola and E. necator, by scoring different parameters of pathogen development. A quantitative trait locus (QTL) analysis allowed us to highlight a major QTL on linkage group 14 controlling resistance to powdery mildew, which explained up to 58 % of the total phenotypic variance. This QTL was named 'Resistance to Erysiphe Necator 5' (Ren5). A microscopic evaluation E. necator mycelium development on resistant and susceptible genotypes of the S1 progeny showed that Ren5 exerts its action after the formation of the first appressorium, and acts by delaying, and then stopping, mycelium development.

  8. Distributive Conjugal Transfer in Mycobacteria Generates Progeny with Meiotic-Like Genome-Wide Mosaicism, Allowing Mapping of a Mating Identity Locus

    PubMed Central

    Gray, Todd A.; Krywy, Janet A.; Harold, Jessica; Palumbo, Michael J.; Derbyshire, Keith M.

    2013-01-01

    Horizontal gene transfer (HGT) in bacteria generates variation and drives evolution, and conjugation is considered a major contributor as it can mediate transfer of large segments of DNA between strains and species. We previously described a novel form of chromosomal conjugation in mycobacteria that does not conform to classic oriT-based conjugation models, and whose potential evolutionary significance has not been evaluated. Here, we determined the genome sequences of 22 F1-generation transconjugants, providing the first genome-wide view of conjugal HGT in bacteria at the nucleotide level. Remarkably, mycobacterial recipients acquired multiple, large, unlinked segments of donor DNA, far exceeding expectations for any bacterial HGT event. Consequently, conjugal DNA transfer created extensive genome-wide mosaicism within individual transconjugants, which generated large-scale sibling diversity approaching that seen in meiotic recombination. We exploited these attributes to perform genome-wide mapping and introgression analyses to map a locus that determines conjugal mating identity in M. smegmatis. Distributive conjugal transfer offers a plausible mechanism for the predicted HGT events that created the genome mosaicism observed among extant Mycobacterium tuberculosis and Mycobacterium canettii species. Mycobacterial distributive conjugal transfer permits innovative genetic approaches to map phenotypic traits and confers the evolutionary benefits of sexual reproduction in an asexual organism. PMID:23874149

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

    SciTech Connect

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

    1991-10-15

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

  10. A molecular map of the apomixis-control locus in Paspalum procurrens and its comparative analysis with other species of Paspalum.

    PubMed

    Hojsgaard, D H; Martínez, E J; Acuña, C A; Quarin, C L; Pupilli, F

    2011-10-01

    Since apomixis was first mapped in Paspalum, the absence of recombination that characterizes the related locus appeared to be the most difficult bottleneck to overcome for the dissection of the genetic determinants that control this trait. An approach to break the block of recombination was developed in this genus through an among-species comparative mapping strategy. A new apomictic species, P. procurrens (Q4094) was crossed with a sexual plant of P. simplex and their progeny was classified for reproductive mode with the aid of morphological, embryological and genetic analyses. On this progeny, a set of heterologous rice RFLP markers strictly co-segregating in coupling phase with apomixis was identified. These markers were all located on the telomeric region of the long arm of the chromosome 12 of rice. In spite of the lack of recombination exhibited by the apomixis-linked markers in P. procurrens, a comparative mapping analysis among P. simplex, P. malacophyllum, P. notatum and P. procurrens, allowed us to identify a small group of markers co-segregating with apomixis in all these species. These markers bracketed a chromosome region that likely contains all the genetic determinants of apomictic reproduction in Paspalum. The implications of this new inter-specific approach for overcoming the block of recombination to isolate the genetic determinants of apomixis and gain a better comprehension of genome structure of apomictic chromosome region are discussed.

  11. Fine scale genetic and physical mapping using interstitial deletion mutants of Lr34 /Yr18: a disease resistance locus effective against multiple pathogens in wheat.

    PubMed

    Spielmeyer, W; Singh, R P; McFadden, H; Wellings, C R; Huerta-Espino, J; Kong, X; Appels, R; Lagudah, E S

    2008-02-01

    The Lr34/Yr18 locus has contributed to durable, non-race specific resistance against leaf rust (Puccinia triticina) and stripe rust (P. striiformis f. sp. tritici) in wheat (Triticum aestivum). Lr34/Yr18 also cosegregates with resistance to powdery mildew (Pm38) and a leaf tip necrosis phenotype (Ltn1). Using a high resolution mapping family from a cross between near-isogenic lines in the "Thatcher" background we demonstrated that Lr34/Yr18 also cosegregated with stem rust resistance in the field. Lr34/Yr18 probably interacts with unlinked genes to provide enhanced stem rust resistance in "Thatcher". In view of the relatively low levels of DNA polymorphism reported in the Lr34/Yr18 region, gamma irradiation of the single chromosome substitution line, Lalbahadur(Parula7D) that carries Lr34/Yr18 was used to generate several mutant lines. Characterisation of the mutants revealed a range of highly informative genotypes, which included variable size deletions and an overlapping set of interstitial deletions. The mutants enabled a large number of wheat EST derived markers to be mapped and define a relatively small physical region on chromosome 7DS that carried Lr34/Yr18. Fine scale genetic mapping confirmed the physical mapping and identified a genetic interval of less than 0.5 cM, which contained Lr34/Yr18. Both rice and Brachypodium genome sequences provided useful information for fine mapping of ESTs in wheat. Gene order was more conserved between wheat and Brachypodium than with rice but these smaller grass genomes did not reveal sequence information that could be used to identify a candidate gene for rust resistance in wheat. We predict that Lr34/Yr18 is located within a large insertion in wheat not found at syntenic positions in Brachypodium and rice.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Construction of a high-resolution linkage map of Rfd1, a restorer-of-fertility locus for cytoplasmic male sterility conferred by DCGMS cytoplasm in radish (Raphanus sativus L.) using synteny between radish and Arabidopsis genomes.

    PubMed

    Cho, Youngcho; Lee, Young-Pyo; Park, Beom-Seok; Han, Tae-Ho; Kim, Sunggil

    2012-08-01

    Cytoplasmic male sterility caused by Dongbu cytoplasmic and genic male-sterility (DCGMS) cytoplasm and its nuclear restorer-of-fertility locus (Rfd1) with a linked molecular marker (A137) have been reported in radish (Raphanus sativus L.). To construct a linkage map of the Rfd1 locus, linked amplified fragment length polymorphism (AFLP) markers were screened using bulked segregant analysis. A 220-bp linked AFLP fragment sequence from radish showed homology with an Arabidopsis coding sequence. Using this Arabidopsis gene sequence, a simple PCR marker (A220) was developed. The A137 and A220 markers flanked the Rfd1 locus. Two homologous Arabidopsis genes with both marker sequences were positioned on Arabidopsis chromosome-3 with an interval of 2.4 Mb. To integrate the Rfd1 locus into a previously reported expressed sequence tag (EST)-simple sequence repeat (SSR) linkage map, the radish EST sequences located in three syntenic blocks within the 2.4-Mb interval were used to develop single nucleotide polymorphism (SNP) markers for tagging each block. The SNP marker in linkage group-2 co-segregated with male fertility in an F(2) population. Using radish ESTs positioned in linkage group-2, five intron length polymorphism (ILP) markers and one cleaved amplified polymorphic sequence (CAPS) marker were developed and used to construct a linkage map of the Rfd1 locus. Two closely linked markers delimited the Rfd1 locus within a 985-kb interval of Arabidopsis chromosome-3. Synteny between the radish and Arabidopsis genomes in the 985-kb interval were used to develop three ILP and three CAPS markers. Two ILP markers further delimited the Rfd1 locus to a 220-kb interval of Arabidopsis chromosome-3.

  17. A locus for axonal motor-sensory neuropathy with deafness and mental retardation maps to Xq26-q27

    SciTech Connect

    Priest, J.M.; Nouri, N.; Keats, B.J.B.

    1994-09-01

    Twenty-two DNA markers spanning the X chromosome have been analyzed for linkage to the locus causing an unusual form of X-linked recessive hereditary motor and sensory neuropathy in a Pennsylvania family of Italian ancestry. This 3 generation family which was originally reported by Cowchock includes 7 affected males, 3 obligate carrier females, and 4 unaffected males. Males are severely affected at birth or within the first few years of life with areflexia, slowly progressive axonal atrophy, and absence of large myelinated fibers, and they all develop pes cavus and hammer toes. Five of the 7 affected males show associated deafness and 3 of these 5 individuals also presented with mental retardation or social developmental delay. Motor nerve conduction velocities in affected males are normal to mildly delayed and sensory conduction velocities are markedly abnormal. Heterozygous females are asymptomatic. Close linkage to the Xg blood group locus (Xp22) was previously excluded in this family while weak linkage of the disease gene to DXYS1 (Xq13-q21) was suggested. The current study excludes the short arm and the proximal long arm of the X chromosome. Haplotype analysis of markers on the long arm demonstrates that HPRT is a proximal flanking marker and that the disease gene is closely linked to the marker DXS984. Further microsatellite markers are being studied in order to refine the region of the distal long arm of the X chromosome containing the gene causing the motor-sensory neuropathy in this family. This is the first such gene assigned to the distal region of Xq.

  18. Mapping and Genetic Structure Analysis of the Anthracnose Resistance Locus Co-1HY in the Common Bean (Phaseolus vulgaris L.)

    PubMed Central

    Wang, Lanfen; Mantri, Nitin; Zhang, Xiaoyan; Zhu, Zhendong; Wang, Shumin

    2017-01-01

    Anthracnose is a destructive disease of the common bean (Phaseolus vulgaris L.). The Andean cultivar Hongyundou has been demonstrated to possess strong resistance to anthracnose race 81. To study the genetics of this resistance, the Hongyundou cultivar was crossed with a susceptible genotype Jingdou. Segregation of resistance for race 81 was assessed in the F2 population and F2:3 lines under controlled conditions. Results indicate that Hongyundou carries a single dominant gene for anthracnose resistance. An allele test by crossing Hongyundou with another resistant cultivar revealed that the resistance gene is in the Co-1 locus (therefore named Co-1HY). The physical distance between this locus and the two flanking markers was 46 kb, and this region included four candidate genes, namely, Phvul.001G243500, Phvul.001G243600, Phvul.001G243700 and Phvul.001G243800. These candidate genes encoded serine/threonine-protein kinases. Expression analysis of the four candidate genes in the resistant and susceptible cultivars under control condition and inoculated treatment revealed that all the four candidate genes are expressed at significantly higher levels in the resistant genotype than in susceptible genotype. Phvul.001G243600 and Phvul.001G243700 are expressed nearly 15-fold and 90-fold higher in the resistant genotype than in the susceptible parent before inoculation, respectively. Four candidate genes will provide useful information for further research into the resistance mechanism of anthracnose in common bean. The closely linked flanking markers identified here may be useful for transferring the resistance allele Co-1HY from Hongyundou to elite anthracnose susceptible common bean lines. PMID:28076395

  19. Mapping and Genetic Structure Analysis of the Anthracnose Resistance Locus Co-1HY in the Common Bean (Phaseolus vulgaris L.).

    PubMed

    Chen, Mingli; Wu, Jing; Wang, Lanfen; Mantri, Nitin; Zhang, Xiaoyan; Zhu, Zhendong; Wang, Shumin

    2017-01-01

    Anthracnose is a destructive disease of the common bean (Phaseolus vulgaris L.). The Andean cultivar Hongyundou has been demonstrated to possess strong resistance to anthracnose race 81. To study the genetics of this resistance, the Hongyundou cultivar was crossed with a susceptible genotype Jingdou. Segregation of resistance for race 81 was assessed in the F2 population and F2:3 lines under controlled conditions. Results indicate that Hongyundou carries a single dominant gene for anthracnose resistance. An allele test by crossing Hongyundou with another resistant cultivar revealed that the resistance gene is in the Co-1 locus (therefore named Co-1HY). The physical distance between this locus and the two flanking markers was 46 kb, and this region included four candidate genes, namely, Phvul.001G243500, Phvul.001G243600, Phvul.001G243700 and Phvul.001G243800. These candidate genes encoded serine/threonine-protein kinases. Expression analysis of the four candidate genes in the resistant and susceptible cultivars under control condition and inoculated treatment revealed that all the four candidate genes are expressed at significantly higher levels in the resistant genotype than in susceptible genotype. Phvul.001G243600 and Phvul.001G243700 are expressed nearly 15-fold and 90-fold higher in the resistant genotype than in the susceptible parent before inoculation, respectively. Four candidate genes will provide useful information for further research into the resistance mechanism of anthracnose in common bean. The closely linked flanking markers identified here may be useful for transferring the resistance allele Co-1HY from Hongyundou to elite anthracnose susceptible common bean lines.

  20. Fine mapping of a multiple sclerosis locus to 2.5 Mb on chromosome 17q22-q24.

    PubMed

    Saarela, Janna; Schoenberg Fejzo, Marlena; Chen, Daniel; Finnilä, Saara; Parkkonen, Maikki; Kuokkanen, Satu; Sobel, Eric; Tienari, Pentti J; Sumelahti, Marja-Liisa; Wikström, Juhani; Elovaara, Irina; Koivisto, Keijo; Pirttilä, Tuula; Reunanen, Mauri; Palotie, Aarno; Peltonen, Leena

    2002-09-15

    Genome-wide linkage analyses performed in a Finnish study sample have identified four potential predisposing loci for multiple sclerosis (MS). Here we made an effort to restrict the wide linkage region on chromosome 17 with a dense set of 31 markers using multipoint linkage analyses and monitoring for shared marker alleles in MS chromosomes. We carried out the linkage analyses in 22 Finnish multiplex MS families originating from a regional subisolate that shows an exceptionally high prevalence of MS in order to minimize the genetic and environmental heterogeneity of the study sample. Thirty markers on the 23 cM initial interval gave positive pairwise LOD scores. We monitored for shared haplotypes among affected family members within a family, and identified an approximately 4 cM region flanked by the markers D17S1792 and ATA43A10 in 17 out of the 22 families (77.3%). The multipoint linkage analyses using Genehunter and SIMWALK 2.40 provided further evidence for the same 4 cM region, for example a maximal multipoint NPL score of 5.98 (P<0.0002). We observed nominal evidence for association to MS, with one marker flanking the shared region, and this association was replicated in the additional set of families. Using the combined power of linkage, association and shared haplotype analyses, we were thus able to restrict the MS locus on chromosome 17q from 23 cM to a 4 cM region covering a physical interval of approximately 2.5 Mb. Thus, this study describes the restriction of an MS locus outside the HLA region into a segment approachable by molecular tools.

  1. A high-resolution linkage map of the Rfd1, a restorer-of-fertility locus for cytoplasmic male sterility in radish (Raphanus sativus L.) produced by a combination of bulked segregant analysis and RNA-Seq.

    PubMed

    Lee, Young-Pyo; Cho, Youngcho; Kim, Sunggil

    2014-10-01

    We utilized a combination of BSA and RNA-Seq to identify SNPs linked to the Rfd1 locus, a restorer-of-fertility gene in radish. A high-density linkage map was constructed using this approach. Male fertility of cytoplasmic male sterility conditioned by the Dongbu cytoplasmic and genic male-sterility cytoplasm can be restored by a restorer-of-fertility locus, Rfd1, in radish. To construct a high-density linkage map and to identify a candidate gene for the Rfd1 locus, bulked segregant analysis and RNA-seq approaches were combined. A total of 26 and 28 million reads produced from male-fertile and male-sterile bulked RNA were mapped to the radish reference unigenes. After stringent screening of SNPs, 327 reliable SNPs of 109 unigenes were selected. Arabidopsis homologs for 101 of the 109 genes were clustered around the 4,000 kb region of Arabidopsis chromosome 3, which was syntenic to the Rfd1 flanking region. Since the reference unigene set was incomplete, the contigs were de novo assembled to identify 134 contigs harboring SNPs. Most of SNP-containing contigs were also clustered on the same syntenic region in Arabidopsis chromosome. A total of 21 molecular markers positioned within a 2.1 cM interval including the Rfd1 locus were developed, based on the selected unigenes and contigs. A segregating population consisting of 10,459 individuals was analyzed to identify recombinants containing crossovers within this interval. A total of 284 identified recombinants were then used to construct a high-density map, which delimited the Rfd1 locus into an 83-kb syntenic interval of Arabidopsis chromosome 3. Since no candidate gene, such as a pentatricopeptide repeat (PPR)-coding gene, was found in this interval, 231 unigenes and 491 contigs containing putative PPR motifs were analyzed further, but no PPR gene in linkage disequilibrium with the Rfd1 locus could be found.

  2. Fine mapping of qRC10-2, a quantitative trait locus for cold tolerance of rice roots at seedling and mature stages.

    PubMed

    Xiao, Ning; Huang, Wei-Nan; Zhang, Xiao-Xiang; Gao, Yong; Li, Ai-Hong; Dai, Yi; Yu, Ling; Liu, Guang-Qing; Pan, Cun-Hong; Li, Yu-Hong; Dai, Zheng-Yuan; Chen, Jian-Min

    2014-01-01

    Cold stress causes various injuries to rice seedlings in low-temperature and high-altitude areas and is therefore an important factor affecting rice production in such areas. In this study, root conductivity (RC) was used as an indicator to map quantitative trait loci (QTLs) of cold tolerance in Oryza rufipogon Griff., Dongxiang wild rice (DX), at its two-leaf stage. The correlation coefficients between RC and the plant survival rate (PSR) at the seedling and maturity stages were -0.85 and -0.9 (P = 0.01), respectively, indicating that RC is a reliable index for evaluating cold tolerance of rice. A preliminary mapping group was constructed from 151 BC2F1 plants using DX as a cold-tolerant donor and the indica variety Nanjing 11 (NJ) as a recurrent parent. A total of 113 codominant simple-sequence repeat (SSR) markers were developed, with a parental polymorphism of 17.3%. Two cold-tolerant QTLs, named qRC10-1 and qRC10-2 were detected on chromosome 10 by composite interval mapping. qRC10-1 (LOD = 3.1, RM171-RM1108) was mapped at 148.3 cM, and qRC10-2 (LOD = 6.1, RM25570-RM304) was mapped at 163.3 cM, which accounted for 9.4% and 32.1% of phenotypic variances, respectively. To fine map the major locus qRC10-2, NJ was crossed with a BC4F2 plant (L188-3), which only carried the QTL qRC10-2, to construct a large BC5F2 fine-mapping population with 13,324 progenies. Forty-five molecular markers were designed to evenly cover qRC10-2, and 10 markers showed polymorphisms between DX and NJ. As a result, qRC10-2 was delimited to a 48.5-kb region between markers qc45 and qc48. In this region, Os10g0489500 and Os10g0490100 exhibited different expression patterns between DX and NJ. Our results provide a basis for identifying the gene(s) underlying qRC10-2, and the markers developed here may be used to improve low-temperature tolerance of rice seedling and maturity stages via marker-assisted selection (MAS). With root electrical conductivity used as a cold

  3. Linkage disequilibrium analysis by searching for shared segments: Mapping a locus for benign recurrent intrahepatic cholestasis (BRIC)

    SciTech Connect

    Freimer, N.; Baharloo, S.; Blankenship, K.

    1994-09-01

    The lod score method of linkage analysis has two important drawbacks: parameters must be specified for the transmission of the disease (e.g. penetrance), and large numbers of genetically informative individuals must be studied. Although several robust non-parametric methods are available, these also require large sample sizes. The availability of dense genetic maps permits genome screening to be conducted by linkage disequilibrium (LD) mapping methods, which are statistically powerful and non-parametric. Lander & Botstein proposed that LD mapping could be employed to screen the human genome for disease loci; we have now applied this strategy to map a gene for an autosomal recessive disorder, benign recurrent intrahepatic cholestatis (BRIC). Our approach to LD mapping was based on identifying chromosome segments shared between distantly related patients; we used 256 microsatellite markers to genotype three affected individuals, and their parents, from an isolated town in The Netherlands. Because endogamy occurred in this population for several generations, all of the BRIC patients are known to be distantly related to each other, but the pedigree structure and connections could not be certainly established more than three generations before the present, so lod score analysis was impossible. A 20 cM region on chromosome 18 is shared by 5/6 patient chromosomes; subsequently, we noted that 6/6 chromosomes shared an interval of about 3 cM in this region. Calculations indicate that it is extremely unlikely that such a region could be inherited by chance rather than by descent from a common ancestor. Thus, LD mapping by searching for shared chromosomal segments is an extremely powerful approach for genome screening to identify disease loci.

  4. The First High-Density Genetic Map Construction in Tree Peony (Paeonia Sect. Moutan) using Genotyping by Specific-Locus Amplified Fragment Sequencing

    PubMed Central

    Cai, Changfu; Cheng, Fang-Yun; Wu, Jing; Zhong, Yuan; Liu, Gaixiu

    2015-01-01

    Genetic linkage maps, permitting the elucidation of genome structure, are one of most powerful genomic tools to accelerate marker-assisted breeding. However, due to a lack of sufficient user-friendly molecular markers, no genetic linkage map has been developed for tree peonies (Paeonia Sect. Moutan), a group of important horticultural plants worldwide. Specific-locus amplified fragment sequencing (SLAF-seq) is a recent molecular marker development technology that enable the large-scale discovery and genotyping of sequence-based marker in genome-wide. In this study, we performed SLAF sequencing of an F1 population, derived from the cross P. ostti ‘FenDanBai’ × P. × suffruticosa ‘HongQiao’, to identify sufficient high-quality markers for the construction of high-density genetic linkage map in tree peonies. After SLAF sequencing, a total of 78 Gb sequencing data and 285,403,225 pair-end reads were generated. We detected 309,198 high-quality SLAFs from these data, of which 85,124 (27.5%) were polymorphic. Subsequently, 3518 of the polymorphic markers, which were successfully encoded in to Mendelian segregation types, and were in conformity with the criteria of high-quality markers, were defined as effective markers and used for genetic linkage mapping. Finally, we constructed an integrated genetic map, which comprised 1189 markers on the five linkage groups, and spanned 920.699 centiMorgans (cM) with an average inter-marker distance of 0.774 cM. There were 1115 ‘SNP-only’ markers, 18 ‘InDel-only’ markers, and 56 ‘SNP&InDel’ markers on the map. Among these markers, 450 (37.85%) showed significant segregation distortion (P < 0.05). In conclusion, this investigation reported the first large-scale marker development and high-density linkage map construction for tree peony. The results of this study will serve as a solid foundation not only for marker-assisted breeding, but also for genome sequence assembly for tree peony. PMID:26010095

  5. The First High-Density Genetic Map Construction in Tree Peony (Paeonia Sect. Moutan) using Genotyping by Specific-Locus Amplified Fragment Sequencing.

    PubMed

    Cai, Changfu; Cheng, Fang-Yun; Wu, Jing; Zhong, Yuan; Liu, Gaixiu

    2015-01-01

    Genetic linkage maps, permitting the elucidation of genome structure, are one of most powerful genomic tools to accelerate marker-assisted breeding. However, due to a lack of sufficient user-friendly molecular markers, no genetic linkage map has been developed for tree peonies (Paeonia Sect. Moutan), a group of important horticultural plants worldwide. Specific-locus amplified fragment sequencing (SLAF-seq) is a recent molecular marker development technology that enable the large-scale discovery and genotyping of sequence-based marker in genome-wide. In this study, we performed SLAF sequencing of an F1 population, derived from the cross P. ostti 'FenDanBai' × P. × suffruticosa 'HongQiao', to identify sufficient high-quality markers for the construction of high-density genetic linkage map in tree peonies. After SLAF sequencing, a total of 78 Gb sequencing data and 285,403,225 pair-end reads were generated. We detected 309,198 high-quality SLAFs from these data, of which 85,124 (27.5%) were polymorphic. Subsequently, 3518 of the polymorphic markers, which were successfully encoded in to Mendelian segregation types, and were in conformity with the criteria of high-quality markers, were defined as effective markers and used for genetic linkage mapping. Finally, we constructed an integrated genetic map, which comprised 1189 markers on the five linkage groups, and spanned 920.699 centiMorgans (cM) with an average inter-marker distance of 0.774 cM. There were 1115 'SNP-only' markers, 18 'InDel-only' markers, and 56 'SNP&InDel' markers on the map. Among these markers, 450 (37.85%) showed significant segregation distortion (P < 0.05). In conclusion, this investigation reported the first large-scale marker development and high-density linkage map construction for tree peony. The results of this study will serve as a solid foundation not only for marker-assisted breeding, but also for genome sequence assembly for tree peony.

  6. An evaluation of genotyping by sequencing (GBS) to map the Breviaristatum-e (ari-e) locus in cultivated barley

    USDA-ARS?s Scientific Manuscript database

    We explored the use of genotyping by sequencing (GBS) on a recombinant inbred line population (GPMx) derived from a cross between the two-rowed barley cultivar ‘Golden Promise’ (ari-e.GP/Vrs1) and the six-rowed cultivar ‘Morex’ (Ari-e/vrs1) to map plant height. We identified three Quantitative Trait...

  7. Next Generation Genetic Mapping of the Ligon-lintless-2 (Li2) Locus in Upland Cotton (Gossypium hirsutum L.)

    USDA-ARS?s Scientific Manuscript database

    Next generation sequencing offers new ways to identify the genetic mechanisms that underlie mutant phenotypes. The release of a reference diploid Gossypium raimondii (D5) genome and bioinformatics tools to sort tetraploid reads into subgenomes has brought cotton genetic mapping into the genomics er...

  8. Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer.

    PubMed Central

    Bignell, G R; Canzian, F; Shayeghi, M; Stark, M; Shugart, Y Y; Biggs, P; Mangion, J; Hamoudi, R; Rosenblatt, J; Buu, P; Sun, S; Stoffer, S S; Goldgar, D E; Romeo, G; Houlston, R S; Narod, S A; Stratton, M R; Foulkes, W D

    1997-01-01

    Thyroid goiter is a common condition that is often associated with iodine deficiency. Familial forms of goiter in areas not known to feature iodine deficiency are much less common. We have performed a genomic search on a single large Canadian family with 18 cases of nontoxic multinodular goiter in which 2 individuals also had papillary lesions highly suggestive of papillary carcinoma. A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at the same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary). The gene encoding thyroid-stimulating hormone receptor (TSHR), which is located on chromosome 14q, is outside the linked region. To determine the role of this gene in familial nonmedullary thyroid cancer (NMTC), we studied 37 smaller pedigrees each containing at least two cases of NMTC. Analysis by both parametric and nonparametric methods indicates that only a very small proportion of familial NMTC (point estimate 0.001, support intervals 0-.6 under a dominant model) is attributable to MNG1. PMID:9345104

  9. Genetic mapping of Eutr1, a locus controlling E2-induced pyometritis in the Brown Norway rat, to RNO5.

    PubMed

    Gould, Karen A; Pandey, Jyotsna; Lachel, Cynthia M; Murrin, Clare R; Flood, Lisa A; Pennington, Karen L; Schaffer, Beverly S; Tochacek, Martin; McComb, Rodney D; Meza, Jane L; Wendell, Douglas L; Shull, James D

    2005-11-01

    In certain rat strains, chronic estrogen administration can lead to pyometritis, an inflammation of the uterus accompanied by infection and the accumulation of intraluminal pus. In this article, we report that the Brown Norway (BN) rat is highly susceptible to pyometritis induced by 17beta-estradiol (E2). The susceptibility of the BN rat to E2-induced pyometritis appears to segregate as a recessive trait in crosses to the resistant August x Copenhagen Irish (ACI) strain. In a (BN x ACI)F(2) population, we find strong evidence for a major genetic determinant of susceptibility to E2-induced pyometritis on rat chromosome 5 (RNO5). Our data are most consistent with a model in which the BN allele of this locus, designated Eutr1 (Estrogen-induced uterine response 1), acts in an incompletely dominant manner to control E2-induced pyometritis. Furthermore, we have confirmed the contribution of Eutr1 to E2-induced uterine pyometritis using an RNO5 congenic rat strain. In addition to Eutr1, we obtained evidence suggestive of linkage for five additional loci on RNO2, 4, 11, 17, and X that control susceptibility to E2-induced pyometritis in the (BN x ACI)F(2) population.

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

    SciTech Connect

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

    1995-08-28

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

  11. The locus for Meckel syndrome with multiple congenital anomalies maps to chromosome 17q21-q24.

    PubMed

    Paavola, P; Salonen, R; Weissenbach, J; Peltonen, L

    1995-10-01

    Autosomal recessive Meckel syndrome (OMIM 249000) (MES), first described in 1822 by Johann F. Meckel, is a major monogenic malformation syndrome with a neural tube defect leading to death of the fetus in utero or shortly after birth. The hallmarks of the syndrome are occipital meningoencephalocele, very large kidneys with multicystic dysplasia, cystic and fibrotic changes of the liver and polydactyly (Fig. 1). Other typical malformations for MES are cleft lip and palate, urinary tract anomalies, ambiguous genitals in the males and club feet. Although MES has been reported worldwide, reports on the true birth prevalence of MES in different populations are scarce. In Finland MES is effectively screened and relatively frequent with a birth prevalence of 1:9,000 and a disease gene frequency of 0.01 (ref.4) which is of the same order of magnitude as that of the most common recessive diseases belonging to the 'Finnish disease heritage', that is genetic disorders enriched or only encountered in Finland. However, in MES, comparable or even higher incidences are also reported from other populations. Here, we report the assignment of the MES locus to chromosome 17q21-q24 in the 13 cM region, and exclude some of the potential candidate genes located in this critical chromosomal region.

  12. Extension, single-locus conversion and physical mapping of sex chromosome sequences identify the Z microchromosome and pseudo-autosomal region in a dragon lizard, Pogona vitticeps.

    PubMed

    Quinn, A E; Ezaz, T; Sarre, S D; Graves, Ja Marshall; Georges, A

    2010-04-01

    Distribution of temperature-dependent sex determination (TSD) and genotypic sex determination (GSD) across the phylogeny of dragon lizards implies multiple independent origins of at least one, and probably both, modes of sex determination. Female Pogona vitticeps are the heterogametic sex, but ZZ individuals reverse to a female phenotype at high incubation temperatures. We used reiterated genome walking to extend Z and W chromosome-linked amplified fragment length polymorphism (AFLP) markers, and fluorescence in situ hybridization for physical mapping. One extended fragment hybridized to both W and Z microchromosomes, identifying the Z microchromosome for the first time, and a second hybridized to the centromere of all microchromosomes. W-linked sequences were converted to a single-locus PCR sexing assay. P. vitticeps sex chromosome sequences also shared homology with several other Australian dragons. Further physical mapping and isolation of sex-specific bacterial artificial chromosome clones will provide insight into the evolution of sex determination and sex chromosomes in GSD and TSD dragon lizards.

  13. Expression Quantitative Trait Locus Mapping Studies in Mid-secretory Phase Endometrial Cells Identifies HLA-F and TAP2 as Fecundability-Associated Genes

    PubMed Central

    Kosova, Gülüm; Patterson, Kristen; Hartmann, Katherine E.; Velez Edwards, Digna R.; Stephenson, Mary D.; Lynch, Vincent J.; Ober, Carole

    2016-01-01

    Fertility traits in humans are heritable, however, little is known about the genes that influence reproductive outcomes or the genetic variants that contribute to differences in these traits between individuals, particularly women. To address this gap in knowledge, we performed an unbiased genome-wide expression quantitative trait locus (eQTL) mapping study to identify common regulatory (expression) single nucleotide polymorphisms (eSNPs) in mid-secretory endometrium. We identified 423 cis-eQTLs for 132 genes that were significant at a false discovery rate (FDR) of 1%. After pruning for strong LD (r2 >0.95), we tested for associations between eSNPs and fecundability (the ability to get pregnant), measured as the length of the interval to pregnancy, in 117 women. Two eSNPs were associated with fecundability at a FDR of 5%; both were in the HLA region and were eQTLs for the TAP2 gene (P = 1.3x10-4) and the HLA-F gene (P = 4.0x10-4), respectively. The effects of these SNPs on fecundability were replicated in an independent sample. The two eSNPs reside within or near regulatory elements in decidualized human endometrial stromal cells. Our study integrating eQTL mapping in a primary tissue with association studies of a related phenotype revealed novel genes and associated alleles with independent effects on fecundability, and identified a central role for two HLA region genes in human implantation success. PMID:27447835

  14. Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

    PubMed Central

    Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud; Kar, Siddhartha; Nord, Silje; Moradi Marjaneh, Mahdi; Soucy, Penny; Michailidou, Kyriaki; Ghoussaini, Maya; Fues Wahl, Hanna; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Alonso, M. Rosario; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Benitez, Javier; Bogdanova, Natalia V.; Bojesen, Stig E.; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Choi, Ji-Yeob; Conroy, Don M.; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Devilee, Peter; Dörk, Thilo; Easton, Douglas F.; Fasching, Peter A.; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G.; Goldberg, Mark S.; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A.; Hallberg, Emily; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L.; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kang, Daehee; Khan, Sofia; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Lambrechts, Diether; Le Marchand, Loic; Lee, Soo Chin; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Mayes, Rebecca; McKay, James; Meindl, Alfons; Milne, Roger L.; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Olswold, Curtis; Orr, Nick; Peterlongo, Paolo; Pita, Guillermo; Pylkäs, Katri; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C.; Stram, Daniel O.; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H.; Tessier, Daniel C.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine M.; Vincent, Daniel; Winqvist, Robert; Wu, Anna H.; Wu, Pei-Ei; Yip, Cheng Har; Zheng, Wei; Pharoah, Paul D. P.; Hall, Per; Edwards, Stacey L.; Simard, Jacques; French, Juliet D.; Chenevix-Trench, Georgia; Dunning, Alison M.

    2016-01-01

    Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90–0.94; P = 8.96 × 10−15)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10−09, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10−11, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus. PMID:27600471

  15. Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs).

    PubMed

    Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud; Kar, Siddhartha; Nord, Silje; Moradi Marjaneh, Mahdi; Soucy, Penny; Michailidou, Kyriaki; Ghoussaini, Maya; Fues Wahl, Hanna; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Alonso, M Rosario; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Benitez, Javier; Bogdanova, Natalia V; Bojesen, Stig E; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Choi, Ji-Yeob; Conroy, Don M; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Devilee, Peter; Dörk, Thilo; Easton, Douglas F; Fasching, Peter A; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G; Goldberg, Mark S; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A; Hallberg, Emily; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kang, Daehee; Khan, Sofia; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Lambrechts, Diether; Le Marchand, Loic; Lee, Soo Chin; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Mayes, Rebecca; McKay, James; Meindl, Alfons; Milne, Roger L; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Olswold, Curtis; Orr, Nick; Peterlongo, Paolo; Pita, Guillermo; Pylkäs, Katri; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H; Tessier, Daniel C; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine M; Vincent, Daniel; Winqvist, Robert; Wu, Anna H; Wu, Pei-Ei; Yip, Cheng Har; Zheng, Wei; Pharoah, Paul D P; Hall, Per; Edwards, Stacey L; Simard, Jacques; French, Juliet D; Chenevix-Trench, Georgia; Dunning, Alison M

    2016-09-07

    Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

  16. Quantitative Trait Locus Based Virulence Determinant Mapping of the HSV-1 Genome in Murine Ocular Infection: Genes Involved in Viral Regulatory and Innate Immune Networks Contribute to Virulence

    PubMed Central

    Larsen, Inna; Craven, Mark; Brandt, Curtis R.

    2016-01-01

    Herpes simplex virus type 1 causes mucocutaneous lesions, and is the leading cause of infectious blindness in the United States. Animal studies have shown that the severity of HSV-1 ocular disease is influenced by three main factors; innate immunity, host immune response and viral strain. We previously showed that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) resulted in recombinants that exhibit a range of disease phenotypes from severe to avirulent, suggesting epistatic interactions were involved. The goal of this study was to develop a quantitative trait locus (QTL) analysis of HSV-1 ocular virulence determinants and to identify virulence associated SNPs. Blepharitis and stromal keratitis quantitative scores were characterized for 40 OD4:CJ994 recombinants. Viral titers in the eye were also measured. Virulence quantitative trait locus mapping (vQTLmap) was performed using the Lasso, Random Forest, and Ridge regression methods to identify significant phenotypically meaningful regions for each ocular disease parameter. The most predictive Ridge regression model identified several phenotypically meaningful SNPs for blepharitis and stromal keratitis. Notably, phenotypically meaningful nonsynonymous variations were detected in the UL24, UL29 (ICP8), UL41 (VHS), UL53 (gK), UL54 (ICP27), UL56, ICP4, US1 (ICP22), US3 and gG genes. Network analysis revealed that many of these variations were in HSV-1 regulatory networks and viral genes that affect innate immunity. Several genes previously implicated in virulence were identified, validating this approach, while other genes were novel. Several novel polymorphisms were also identified in these genes. This approach provides a framework that will be useful for identifying virulence genes in other pathogenic viruses, as well as epistatic effects that affect HSV-1 ocular virulence. PMID:26962864

  17. Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men

    PubMed Central

    Freedman, Matthew L.; Haiman, Christopher A.; Patterson, Nick; McDonald, Gavin J.; Tandon, Arti; Waliszewska, Alicja; Penney, Kathryn; Steen, Robert G.; Ardlie, Kristin; John, Esther M.; Oakley-Girvan, Ingrid; Whittemore, Alice S.; Cooney, Kathleen A.; Ingles, Sue A.; Altshuler, David; Henderson, Brian E.; Reich, David

    2006-01-01

    A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P < 4.2 × 10−9) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it. PMID:16945910

  18. Quantitative trait locus mapping in laboratory mice derived from a replicated selection experiment for open-field activity.

    PubMed Central

    Turri, M G; Henderson, N D; DeFries, J C; Flint, J

    2001-01-01

    Bidirectional selection in rodents has been used to derive animal models of human behavior. An important question is whether selection for behavior operates on a limited number of QTL or whether the number and individual contribution of QTL varies between selection experiments. To address this question, we mapped QTL in two large F2 intercrosses (N = 815 and 821) from the four lines derived from a replicated selection experiment for open-field activity, an animal model for susceptibility to anxiety. Our analyses indicate that selection operated on the same relatively small number of loci in both crosses. Haplotype information and the direction of effect of each QTL allele were used to confirm that the QTL mapped in the two crosses lie in the same chromosomal regions, although we were unable to determine whether QTL in the two crosses represent the same genes. We conclude that the genetic architecture of the selected strains is similar and relatively simple. PMID:11454769

  19. A first AFLP-Based Genetic Linkage Map for Brine Shrimp Artemia franciscana and Its Application in Mapping the Sex Locus

    PubMed Central

    De Vos, Stephanie; Bossier, Peter; Van Stappen, Gilbert; Vercauteren, Ilse; Sorgeloos, Patrick; Vuylsteke, Marnik

    2013-01-01

    We report on the construction of sex-specific linkage maps, the identification of sex-linked markers and the genome size estimation for the brine shrimp Artemia franciscana. Overall, from the analysis of 433 AFLP markers segregating in a 112 full-sib family we identified 21 male and 22 female linkage groups (2n = 42), covering 1,041 and 1,313 cM respectively. Fifteen putatively homologous linkage groups, including the sex linkage groups, were identified between the female and male linkage map. Eight sex-linked AFLP marker alleles were inherited from the female parent, supporting the hypothesis of a WZ–ZZ sex-determining system. The haploid Artemia genome size was estimated to 0.93 Gb by flow cytometry. The produced Artemia linkage maps provide the basis for further fine mapping and exploring of the sex-determining region and are a possible marker resource for mapping genomic loci underlying phenotypic differences among Artemia species. PMID:23469207

  20. A first AFLP-based genetic linkage map for brine shrimp Artemia franciscana and its application in mapping the sex locus.

    PubMed

    De Vos, Stephanie; Bossier, Peter; Van Stappen, Gilbert; Vercauteren, Ilse; Sorgeloos, Patrick; Vuylsteke, Marnik

    2013-01-01

    We report on the construction of sex-specific linkage maps, the identification of sex-linked markers and the genome size estimation for the brine shrimp Artemia franciscana. Overall, from the analysis of 433 AFLP markers segregating in a 112 full-sib family we identified 21 male and 22 female linkage groups (2n = 42), covering 1,041 and 1,313 cM respectively. Fifteen putatively homologous linkage groups, including the sex linkage groups, were identified between the female and male linkage map. Eight sex-linked AFLP marker alleles were inherited from the female parent, supporting the hypothesis of a WZ-ZZ sex-determining system. The haploid Artemia genome size was estimated to 0.93 Gb by flow cytometry. The produced Artemia linkage maps provide the basis for further fine mapping and exploring of the sex-determining region and are a possible marker resource for mapping genomic loci underlying phenotypic differences among Artemia species.

  1. 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.

  2. Admixture mapping scans identify a locus affecting retinal vascular caliber in hypertensive African Americans: the Atherosclerosis Risk in Communities (ARIC) study.

    PubMed

    Cheng, Ching-Yu; Reich, David; Wong, Tien Y; Klein, Ronald; Klein, Barbara E K; Patterson, Nick; Tandon, Arti; Li, Man; Boerwinkle, Eric; Sharrett, A Richey; Kao, W H Linda

    2010-04-15

    Retinal vascular caliber provides information about the structure and health of the microvascular system and is associated with cardiovascular and cerebrovascular diseases. Compared to European Americans, African Americans tend to have wider retinal arteriolar and venular caliber, even after controlling for cardiovascular risk factors. This has suggested the hypothesis that differences in genetic background may contribute to racial/ethnic differences in retinal vascular caliber. Using 1,365 ancestry-informative SNPs, we estimated the percentage of African ancestry (PAA) and conducted genome-wide admixture mapping scans in 1,737 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) representing summary measures of retinal arteriolar and venular caliber, respectively, were measured from retinal photographs. PAA was significantly correlated with CRVE (rho = 0.071, P = 0.003), but not CRAE (rho = 0.032, P = 0.182). Using admixture mapping, we did not detect significant admixture association with either CRAE (genome-wide score = -0.73) or CRVE (genome-wide score = -0.69). An a priori subgroup analysis among hypertensive individuals detected a genome-wide significant association of CRVE with greater African ancestry at chromosome 6p21.1 (genome-wide score = 2.31, locus-specific LOD = 5.47). Each additional copy of an African ancestral allele at the 6p21.1 peak was associated with an average increase in CRVE of 6.14 microm in the hypertensives, but had no significant effects in the non-hypertensives (P for heterogeneity <0.001). Further mapping in the 6p21.1 region may uncover novel genetic variants affecting retinal vascular caliber and further insights into the interaction between genetic effects of the microvascular system and hypertension.

  3. High-resolution mapping and chromosome landing at the root-know nematode resistance locus Ma from Myrobalan plum using a large-insert BAC DNA library.

    PubMed

    Claverie, M; Dirlewanger, E; Cosson, P; Bosselut, N; Lecouls, A C; Voisin, R; Kleinhentz, M; Lafargue, B; Caboche, M; Chalhoub, B; Esmenjaud, D

    2004-10-01

    The Ma gene for root-knot nematode (RKN)resistance from Myrobalan plum (Prunus cerasifera L.)confers a complete-spectrum and a heat-stable resistance to Meloidogvne spp., conversely to Mi-I from tomato,which has a more restricted spectrum and a reduced efficiency at high temperature. This gene was identified from a perennial self-incompatible near-wild rootstock species and lies in cosegregation with the SCAR marker SCAFLP2 on the Prunus linkage group 7 in a 2.3 cM interval between the SCAR SCAL19 and SSR pchgms6 markers. We initiated a map-based cloning of Ma and report here the strategy that rapidly led to fine mapping and direct chromosome landing at the locus. Three pairs of bulks, totaling 90 individuals from half-sibling progenies derived from the Ma-heterozygous resistant accession P.2175, were constructed using mapping data, and saturation of the Ma region was performed by bulked segregant analysis (BSA) of 320 AFLP primer pair combinations. The closest three AFLP markers were transformed into codominant SCARs or CAPS designatedSCAFLP3, SCAFLP4 and SCAFLP5. By completing the mapping population up to 1,332 offspring from P.2175,Ma and SCAFLP2 were mapped in a 0.8 cM interval between SCAFLP3 and SCAFLP4. A large-insert bacterial artificial chromosome (BAC) DNA library of P.2175,totaling 30,720 clones with a mean insert size of 145 kb and a 14-15x Prunus haploid genome coverage was constructed and used to land on the Ma spanning interval with few BAC clones. As P.2175 is heterozygous for the gene, we constructed the resistant and susceptible physical contigs by PCR screening of the library with codominant markers. Additional microsatellite markers were then designed from BAC subcloning or BAC end sequencing. In the resistant contig, a single 280 kb BAC clone was shown to carry the Ma gene; this BAC contains two flanking markers on each side of the gene as well as two cosegregating markers. These results should allow future cloning of the Ma gene in this

  4. 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

  5. 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

  6. Development of a predicted physical map of microsatellite locus positions for pinnipeds, with wider applicability to the Carnivora.

    PubMed

    Osborne, Amy J; Brauning, Rudiger; Schultz, Jennifer K; Kennedy, Martin A; Slate, Jon; Gemmell, Neil J

    2011-05-01

    Understanding genetic variation responsible for phenotypic differences in natural populations is significantly hampered by a lack of genomic data for many species. Levels of variation can, however, be estimated using microsatellite markers, which may be useful for relating individual fitness to genetic diversity. Prior studies have demonstrated correlations between heterozygosity and individual fitness in some species. These correlations are sometimes driven by a subset of markers, and it is unclear whether this is because those markers best reflect genome-wide heterozygosity, or whether they are linked to fitness-related genes. Differentiating between these scenarios is hindered when the genomic location of markers is unknown. Here, we develop a predicted genomic map of pinniped microsatellite loci based on conservation of primary sequence and genomic location between dog, cat and giant panda. We mapped 210 of 260 (81%) microsatellites from pinnipeds to locations in dog, cat and giant panda genomes. Based on the demonstrable synteny between the genomes of closely related taxa within the Carnivora, we use these data to identify those microsatellites with the greatest chance of cross-species amplification success and demonstrate successful amplification of 21 of 26 loci for cat, dog and two seal species. We also demonstrate the potential to identify candidate genes that may underpin the functional relationship with individual fitness. Overall, we show that this approach provides a rapid and robust method to elucidate genome organisation for nonmodel organisms and have established a resource that facilitates further genetic research on pinnipeds that also has wider applicability to other carnivores.

  7. 3D phenotyping and quantitative trait locus mapping identify core regions of the rice genome controlling root architecture.

    PubMed

    Topp, Christopher N; Iyer-Pascuzzi, Anjali S; Anderson, Jill T; Lee, Cheng-Ruei; Zurek, Paul R; Symonova, Olga; Zheng, Ying; Bucksch, Alexander; Mileyko, Yuriy; Galkovskyi, Taras; Moore, Brad T; Harer, John; Edelsbrunner, Herbert; Mitchell-Olds, Thomas; Weitz, Joshua S; Benfey, Philip N

    2013-04-30

    Identification of genes that control root system architecture in crop plants requires innovations that enable high-throughput and accurate measurements of root system architecture through time. We demonstrate the ability of a semiautomated 3D in vivo imaging and digital phenotyping pipeline to interrogate the quantitative genetic basis of root system growth in a rice biparental mapping population, Bala × Azucena. We phenotyped >1,400 3D root models and >57,000 2D images for a suite of 25 traits that quantified the distribution, shape, extent of exploration, and the intrinsic size of root networks at days 12, 14, and 16 of growth in a gellan gum medium. From these data we identified 89 quantitative trait loci, some of which correspond to those found previously in soil-grown plants, and provide evidence for genetic tradeoffs in root growth allocations, such as between the extent and thoroughness of exploration. We also developed a multivariate method for generating and mapping central root architecture phenotypes and used it to identify five major quantitative trait loci (r(2) = 24-37%), two of which were not identified by our univariate analysis. Our imaging and analytical platform provides a means to identify genes with high potential for improving root traits and agronomic qualities of crops.

  8. Cloning and expression analysis of a novel gene, RP42, mapping to an autism susceptibility locus on 6q16.

    PubMed

    Mas, C; Bourgeois, F; Bulfone, A; Levacher, B; Mugnier, C; Simonneau, M

    2000-04-01

    We isolated a novel mouse gene, RP42, in a systematic search for genes expressed in proliferating neuroblasts whose human orthologs map to susceptibility loci for autism. This gene is intronless and encodes a putative 259-amino-acid protein that exhibits 30-36% overall sequence identity to a fission yeast and a nematode protein (GenPept Accession Nos. CAA17006 and CAB54261). Nevertheless, no homology to any known gene was found. RP42 has developmentally regulated expression, particularly in proliferating neuroblasts from which neocortical neurons originate. Its human ortholog is located in a cluster of embryonic neuronally expressed genes on the 6q16 chromosome, making it a positional candidate susceptibility gene for autism.

  9. A diabetes-associated T-cell autoantigen maps to a telomeric locus on mouse chromosome 6.

    PubMed

    Dallas-Pedretti, A; McDuffie, M; Haskins, K

    1995-02-28

    Identification of diabetes-associated T-cell autoantigens is important for understanding the immunopathology of diabetes and developing improved therapeutic strategies. We have used a genetic approach to move toward identifying the autoantigen recognized by a diabetogenic islet-specific T-cell clone from a nonobese diabetic (NOD) mouse. The unique antigen recognition pattern of this clone was utilized to map the gene encoding the antigen (or its expression) by genetic linkage analysis. In vitro analysis of T-cell proliferation by this clone showed that the capacity of the islets to stimulate T cells segregates as a single codominant gene in BALB/cByJ x (BALB/cByJ x NOD/Bdc) backcross mice. This phenotype was tightly linked to two microsatellites in the telomeric region of mouse chromosome 6.

  10. Cultivar-Based Introgression Mapping Reveals Wild Species-Derived Pm-0, the Major Powdery Mildew Resistance Locus in Squash

    PubMed Central

    Holdsworth, William L.; LaPlant, Kyle E.; Bell, Duane C.; Jahn, Molly M.; Mazourek, Michael

    2016-01-01

    Powdery mildew is a major fungal disease on squash and pumpkin (Cucurbita spp.) in the US and throughout the world. Genetic resistance to the disease is not known to occur naturally within Cucurbita pepo and only infrequently in Cucurbita moschata, but has been achieved in both species through the introgression of a major resistance gene from the wild species Cucurbita okeechobeensis subsp. martinezii. At present, this gene, Pm-0, is used extensively in breeding, and is found in nearly all powdery mildew-resistant C. pepo and C. moschata commercial cultivars. In this study, we mapped C. okeechobeensis subsp. martinezii-derived single nucleotide polymorphism (SNP) alleles in a set of taxonomically and morphologically diverse and resistant C. pepo and C. moschata cultivars bred at Cornell University that, by common possession of Pm-0, form a shared-trait introgression panel. High marker density was achieved using genotyping-by-sequencing, which yielded over 50,000 de novo SNP markers in each of the three Cucurbita species genotyped. A single 516.4 kb wild-derived introgression was present in all of the resistant cultivars and absent in a diverse set of heirlooms that predated the Pm-0 introgression. The contribution of this interval to powdery mildew resistance was confirmed by association mapping in a C. pepo cultivar panel that included the Cornell lines, heirlooms, and 68 additional C. pepo cultivars and with an independent F2 population derived from C. okeechobeensis subsp. martinezii x C. moschata. The interval was refined to a final candidate interval of 76.4 kb and CAPS markers were developed inside this interval to facilitate marker-assisted selection. PMID:27936008

  11. Fine mapping of shattering locus Br2 reveals a putative chromosomal inversion polymorphism between the two lineages of Aegilops tauschii.

    PubMed

    Zhang, Zhengzhi; Zhu, Huilan; Gill, Bikram S; Li, Wanlong

    2015-04-01

    This work laid the foundation for cloning of shattering gene Br2 and provided first line of evidence that two major Aegilops tauschii lineages are differentiated by an inversion polymorphism. Chromosome inversions often accompany population differentiation and capture local adaptation during speciation. Aegilops tauschii, the D-genome donor species of hexaploid wheat, consists of two genetically isolated lineages, L1 and L2, but little is known about the genetic mechanisms underlying the population differentiation in this diploid species. During fine mapping of the shattering gene Br2 using a large F2 population derived from a cross between TA1604 (an L1 accession) and AL8/78 (an L2 accession), we found contrasting patterns of crossover distribution in the Br2 interval and neighboring regions despite the high local gene synteny with Brachypodium distachyon and rice. Br2 was localized in a 0.08-cM interval, and 13 marker loci formed a block, where single-crossovers were completely suppressed, but double-crossovers were enriched with a recombination rate of ~11 cM/Mb. In contrast, in a neighboring region no double-crossover was recovered, but single-crossover rate reached 24 cM/Mb, which is much higher than the genome-wide average. This result suggests a putative inversion polymorphism between the parental lines in the Br2 region. Genotyping using the markers from the Br2 region divided a collection of 55 randomly sampled A. tauschii accessions into two major groups, and they are largely genetically isolated. The two groups correspond to the L1 and L2 lineages based on their geographic distribution patterns. This provides first evidence that inversions may underlie the evolution of A. tauschii lineages. The presence of inter-lineage inversions may complicate map-based cloning in A. tauschii and transfer of useful traits to wheat.

  12. Cultivar-Based Introgression Mapping Reveals Wild Species-Derived Pm-0, the Major Powdery Mildew Resistance Locus in Squash.

    PubMed

    Holdsworth, William L; LaPlant, Kyle E; Bell, Duane C; Jahn, Molly M; Mazourek, Michael

    2016-01-01

    Powdery mildew is a major fungal disease on squash and pumpkin (Cucurbita spp.) in the US and throughout the world. Genetic resistance to the disease is not known to occur naturally within Cucurbita pepo and only infrequently in Cucurbita moschata, but has been achieved in both species through the introgression of a major resistance gene from the wild species Cucurbita okeechobeensis subsp. martinezii. At present, this gene, Pm-0, is used extensively in breeding, and is found in nearly all powdery mildew-resistant C. pepo and C. moschata commercial cultivars. In this study, we mapped C. okeechobeensis subsp. martinezii-derived single nucleotide polymorphism (SNP) alleles in a set of taxonomically and morphologically diverse and resistant C. pepo and C. moschata cultivars bred at Cornell University that, by common possession of Pm-0, form a shared-trait introgression panel. High marker density was achieved using genotyping-by-sequencing, which yielded over 50,000 de novo SNP markers in each of the three Cucurbita species genotyped. A single 516.4 kb wild-derived introgression was present in all of the resistant cultivars and absent in a diverse set of heirlooms that predated the Pm-0 introgression. The contribution of this interval to powdery mildew resistance was confirmed by association mapping in a C. pepo cultivar panel that included the Cornell lines, heirlooms, and 68 additional C. pepo cultivars and with an independent F2 population derived from C. okeechobeensis subsp. martinezii x C. moschata. The interval was refined to a final candidate interval of 76.4 kb and CAPS markers were developed inside this interval to facilitate marker-assisted selection.

  13. Expression Quantitative Trait Locus Mapping across Water Availability Environments Reveals Contrasting Associations with Genomic Features in Arabidopsis[C][W][OPEN

    PubMed Central

    Lowry, David B.; Logan, Tierney L.; Santuari, Luca; Hardtke, Christian S.; Richards, James H.; DeRose-Wilson, Leah J.; McKay, John K.; Sen, Saunak; Juenger, Thomas E.

    2013-01-01

    The regulation of gene expression is crucial for an organism’s development and response to stress, and an understanding of the evolution of gene expression is of fundamental importance to basic and applied biology. To improve this understanding, we conducted expression quantitative trait locus (eQTL) mapping in the Tsu-1 (Tsushima, Japan) × Kas-1 (Kashmir, India) recombinant inbred line population of Arabidopsis thaliana across soil drying treatments. We then used genome resequencing data to evaluate whether genomic features (promoter polymorphism, recombination rate, gene length, and gene density) are associated with genes responding to the environment (E) or with genes with genetic variation (G) in gene expression in the form of eQTLs. We identified thousands of genes that responded to soil drying and hundreds of main-effect eQTLs. However, we identified very few statistically significant eQTLs that interacted with the soil drying treatment (GxE eQTL). Analysis of genome resequencing data revealed associations of several genomic features with G and E genes. In general, E genes had lower promoter diversity and local recombination rates. By contrast, genes with eQTLs (G) had significantly greater promoter diversity and were located in genomic regions with higher recombination. These results suggest that genomic architecture may play an important a role in the evolution of gene expression. PMID:24045022

  14. Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus

    SciTech Connect

    Kwon, B.S.; Haq, A.K.; Pomerantz, S.H.; Halaban, R.

    1987-11-01

    Screening of a lambdagt11 human melanocyte cDNA library with antibodies against hamster tyrosinase resulted in the isolation of 16 clones. The cDNA inserts from 13 of the 16 clones cross-hybridized with each other, indicating that they were form related mRNA species. One of the cDNA clones, Pmel34, detected one mRNA species with an approximate length of 2.4 kilobases that was expressed preferentially in normal and malignant melanocytes but not in other cell types. The amino acid sequence deduced from the nucleotide sequence showed that the putative human tyrosinase is composed of 548 amino acids with a molecular weight of 62,610. The deduced protein contains glycosylation sites and histidine-rich sites that could be used for copper binding. Southern blot analysis of DNA derived from newborn mice carrying lethal albino deletion mutations revealed that Pmel34 maps near or at the c-albino locus, the position of the structural gene for tyrosinase.

  15. The novel, major locus Rpi-phu1 for late blight resistance maps to potato chromosome IX and is not correlated with long vegetation period.

    PubMed

    Sliwka, J; Jakuczun, H; Lebecka, R; Marczewski, W; Gebhardt, C; Zimnoch-Guzowska, E

    2006-08-01

    Despite the long history of breeding potatoes resistant to Phytophthora infestans, this oomycete is still economically the most important pathogen of potato worldwide. The correlation of high levels of resistance to late blight with a long vegetation period is one of the bottlenecks for progress in breeding resistant cultivars of various maturity types. Solanum phureja was identified as a source of effective late blight resistance, which was transferred to the cultivated gene pool by interspecific crosses with dihaploids of Solanum tuberosum. A novel major resistance locus, Rpi-phu1, derived most likely from S. phureja and conferring broad-spectrum resistance to late blight, was mapped to potato chromosome IX, 6.4 cM proximal to the marker GP94. Rpi-phu1 was highly effective in detached leaflet, tuber slice and whole tuber tests during 5 years of quantitative phenotypic assessment. The resistance did not show significant correlation with vegetation period length. Our findings provide a well-characterized new source of resistance for breeding early and resistant-to-P. infestans potatoes.

  16. Quantitative Trait Locus Mapping of Yield-Related Components and Oligogenic Control of the Cap Color of the Button Mushroom, Agaricus bisporus

    PubMed Central

    Rodier, Anne; Rousseau, Thierry; Savoie, Jean-Michel

    2012-01-01

    As in other crops, yield is an important trait to be selected for in edible mushrooms, but its inheritance is poorly understood. Therefore, we have investigated the complex genetic architecture of yield-related traits in Agaricus bisporus through the mapping of quantitative trait loci (QTL), using second-generation hybrid progeny derived from a cross between a wild strain and a commercial cultivar. Yield, average weight per mushroom, number of fruiting bodies per m2, earliness, and cap color were evaluated in two independent experiments. A total of 23 QTL were detected for 7 yield-related traits. These QTL together explained between 21% (two-flushes yield) and 59% (earliness) of the phenotypic variation. Fifteen QTL (65%) were consistent between the two experiments. Four regions underlying significant QTL controlling yield, average weight, and number were detected on linkage groups II, III, IV, and X, suggesting a pleiotropic effect or tight linkage. Up to six QTL were identified for earliness. The PPC1 locus, together with two additional genomic regions, explained up to 90% of the phenotypic variation of the cap color. Alleles from the wild parent showed beneficial effects for some yield traits, suggesting that the wild germ plasm is a valuable source of variation for several agronomic traits. Our results constitute a key step toward marker-assisted selection and provide a solid foundation to go further into the biological mechanisms controlling productive traits in the button mushroom. PMID:22267676

  17. 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.

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

    PubMed

    Belmouden, A; Adam, M F; Dupont de Dinechin, S; Brézin, A P; Rigault, P; Chumakov, I; Bach, J F; Garchon, H J

    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 (ATP1B1, ATP2B4, ATP1A2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify the GLC1A gene.

  19. Substitution mapping of dth1.1, a flowering-time quantitative trait locus (QTL) associated with transgressive variation in rice, reveals multiple sub-QTL.

    PubMed

    Thomson, Michael J; Edwards, Jeremy D; Septiningsih, Endang M; Harrington, Sandra E; McCouch, Susan R

    2006-04-01

    A quantitative trait locus (QTL), dth1.1, was associated with transgressive variation for days to heading in an advanced backcross population derived from the Oryza sativa variety Jefferson and an accession of the wild rice relative Oryza rufipogon. A series of near-isogenic lines (NILs) containing different O. rufipogon introgressions across the target region were constructed to dissect dth1.1 using substitution mapping. In contrast to the late-flowering O. rufipogon parent, O. rufipogon alleles in the substitution lines caused early flowering under both short- and long-day lengths and provided evidence for at least two distinct sub-QTL: dth1.1a and dth1.1b. Potential candidate genes underlying these sub-QTL include genes with sequence similarity to Arabidopsis GI, FT, SOC1, and EMF1, and Pharbitis nil PNZIP. Evidence from families with nontarget O. rufipogon introgressions in combination with dth1.1 alleles also detected an early flowering QTL on chromosome 4 and a late-flowering QTL on chromosome 6 and provided evidence for additional sub-QTL in the dth1.1 region. The availability of a series of near-isogenic lines with alleles introgressed from a wild relative of rice provides an opportunity to better understand the molecular basis of transgressive variation in a quantitative trait.

  20. Substitution Mapping of dth1.1, a Flowering-Time Quantitative Trait Locus (QTL) Associated With Transgressive Variation in Rice, Reveals Multiple Sub-QTL

    PubMed Central

    Thomson, Michael J.; Edwards, Jeremy D.; Septiningsih, Endang M.; Harrington, Sandra E.; McCouch, Susan R.

    2006-01-01

    A quantitative trait locus (QTL), dth1.1, was associated with transgressive variation for days to heading in an advanced backcross population derived from the Oryza sativa variety Jefferson and an accession of the wild rice relative Oryza rufipogon. A series of near-isogenic lines (NILs) containing different O. rufipogon introgressions across the target region were constructed to dissect dth1.1 using substitution mapping. In contrast to the late-flowering O. rufipogon parent, O. rufipogon alleles in the substitution lines caused early flowering under both short- and long-day lengths and provided evidence for at least two distinct sub-QTL: dth1.1a and dth1.1b. Potential candidate genes underlying these sub-QTL include genes with sequence similarity to Arabidopsis GI, FT, SOC1, and EMF1, and Pharbitis nil PNZIP. Evidence from families with nontarget O. rufipogon introgressions in combination with dth1.1 alleles also detected an early flowering QTL on chromosome 4 and a late-flowering QTL on chromosome 6 and provided evidence for additional sub-QTL in the dth1.1 region. The availability of a series of near-isogenic lines with alleles introgressed from a wild relative of rice provides an opportunity to better understand the molecular basis of transgressive variation in a quantitative trait. PMID:16452146

  1. Systematic Fine-Mapping of Association with BMI and Type 2 Diabetes at the FTO Locus by Integrating Results from Multiple Ethnic Groups

    PubMed Central

    Chakrawarthy, Sureka; Nguyen, Quang Ngoc; Wen, Wanqing; Yamamoto, Ken; Katsuya, Tomohiro; Kasturiratne, Anuradhani; Pham, Son Thai; Zheng, Wei; Matsushita, Yumi; Kishimoto, Miyako; Do, Loi Doan; Shu, Xiao-Ou; Wickremasinghe, Ananda R.; Kajio, Hiroshi; Kato, Norihiro

    2014-01-01

    Background/Objective The 16q12.2 locus in the first intron of FTO has been robustly associated with body mass index (BMI) and type 2 diabetes in genome-wide association studies (GWAS). To improve the resolution of fine-scale mapping at FTO, we performed a systematic approach consisting of two parts. Methods The first part is to partition the associated variants into linkage disequilibrium (LD) clusters, followed by conditional and haplotype analyses. The second part is to filter the list of potential causal variants through trans-ethnic comparison. Results We first examined the LD relationship between FTO SNPs showing significant association with type 2 diabetes in Japanese GWAS and between those previously reported in European GWAS. We could partition all the assayed or imputed SNPs showing significant association in the target FTO region into 7 LD clusters. Assaying 9 selected SNPs in 4 Asian-descent populations—Japanese, Vietnamese, Sri Lankan and Chinese (n≤26,109 for BMI association and n≤24,079 for type 2 diabetes association), we identified a responsible haplotype tagged by a cluster of SNPs and successfully narrowed the list of potential causal variants to 25 SNPs, which are the smallest in number among the studies conducted to date for FTO. Conclusions Our data support that the power to resolve the causal variants from those in strong LD increases consistently when three distant populations—Europeans, Asians and Africans—are included in the follow-up study. It has to be noted that this fine-mapping approach has the advantage of applicability to the existing GWAS data set in combination with direct genotyping of selected variants. PMID:24978468

  2. Bifurcations of the conjugate locus

    NASA Astrophysics Data System (ADS)

    Waters, Thomas

    2017-09-01

    The conjugate locus of a point p in a surface S will have a certain number of cusps. As the point p is moved in the surface the conjugate locus may spontaneously gain or lose cusps. In this paper we explain this 'bifurcation' in terms of the vanishing of higher derivatives of the exponential map; we derive simple equations for these higher derivatives in terms of scalar invariants; we classify the bifurcations of cusps in terms of the local structure of the conjugate locus; and we describe an intuitive picture of the bifurcation as the intersection between certain contours in the tangent plane.

  3. Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer.

    PubMed

    Shi, Jiajun; Zhang, Yanfeng; Zheng, Wei; Michailidou, Kyriaki; Ghoussaini, Maya; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Lush, Michael; Milne, Roger L; Shu, Xiao-Ou; Beesley, Jonathan; Kar, Siddhartha; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Zhao, Zhiguo; Guo, Xingyi; Benitez, Javier; Beeghly-Fadiel, Alicia; Blot, William; Bogdanova, Natalia V; Bojesen, Stig E; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Cai, Hui; Canisius, Sander; Chang-Claude, Jenny; Choi, Ji-Yeob; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Droit, Arnaud; Dork, Thilo; Fasching, Peter A; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gaborieau, Valerie; García-Closas, Montserrat; Giles, Graham G; Grip, Mervi; Guenel, Pascal; Haiman, Christopher A; Hamann, Ute; Hartman, Mikael; Miao, Hui; Hollestelle, Antoinette; Hopper, John L; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Torres, Diana; Kabisch, Maria; Kang, Daehee; Khan, Sofia; Knight, Julia A; Kosma, Veli-Matti; Lambrechts, Diether; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; McLean, Catriona; Meindl, Alfons; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Nord, Silje; Børresen-Dale, Anne-Lise; Olson, Janet E; Orr, Nick; van den Ouweland, Ans M W; Peterlongo, Paolo; Choudary Putti, Thomas; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Shen, Chen-Yang; Hou, Ming-Feng; Shrubsole, Matha J; Southey, Melissa C; Swerdlow, Anthony; Hwang Teo, Soo; Thienpont, Bernard; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Therese; Tseng, Chiu-Chen; Wen, Wanqing; Winqvist, Robert; Wu, Anna H; Har Yip, Cheng; Zamora, Pilar M; Zheng, Ying; Floris, Giuseppe; Cheng, Ching-Yu; Hooning, Maartje J; Martens, John W M; Seynaeve, Caroline; Kristensen, Vessela N; Hall, Per; Pharoah, Paul D P; Simard, Jacques; Chenevix-Trench, Georgia; Dunning, Alison M; Antoniou, Antonis C; Easton, Douglas F; Cai, Qiuyin; Long, Jirong

    2016-09-15

    Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.

  4. 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

  5. Quantitative Trait Locus Mapping and Candidate Gene Analysis for Plant Architecture Traits Using Whole Genome Re-Sequencing in Rice

    PubMed Central

    Lim, Jung-Hyun; Yang, Hyun-Jung; Jung, Ki-Hong; Yoo, Soo-Cheul; Paek, Nam-Chon

    2014-01-01

    Plant breeders have focused on improving plant architecture as an effective means to increase crop yield. Here, we identify the main-effect quantitative trait loci (QTLs) for plant shape-related traits in rice (Oryza sativa) and find candidate genes by applying whole genome re-sequencing of two parental cultivars using next-generation sequencing. To identify QTLs influencing plant shape, we analyzed six traits: plant height, tiller number, panicle diameter, panicle length, flag leaf length, and flag leaf width. We performed QTL analysis with 178 F7 recombinant in-bred lines (RILs) from a cross of japonica rice line ‘SNUSG1’ and indica rice line ‘Milyang23’. Using 131 molecular markers, including 28 insertion/deletion markers, we identified 11 main- and 16 minor-effect QTLs for the six traits with a threshold LOD value > 2.8. Our sequence analysis identified fifty-four candidate genes for the main-effect QTLs. By further comparison of coding sequences and meta-expression profiles between japonica and indica rice varieties, we finally chose 15 strong candidate genes for the 11 main-effect QTLs. Our study shows that the whole-genome sequence data substantially enhanced the efficiency of polymorphic marker development for QTL fine-mapping and the identification of possible candidate genes. This yields useful genetic resources for breeding high-yielding rice cultivars with improved plant architecture. PMID:24599000

  6. Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

    PubMed Central

    Glubb, Dylan M.; Maranian, Mel J.; Michailidou, Kyriaki; Pooley, Karen A.; Meyer, Kerstin B.; Kar, Siddhartha; Carlebur, Saskia; O’Reilly, Martin; Betts, Joshua A.; Hillman, Kristine M.; Kaufmann, Susanne; Beesley, Jonathan; Canisius, Sander; Hopper, John L.; Southey, Melissa C.; Tsimiklis, Helen; Apicella, Carmel; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B.; van der Schoot, C. Ellen; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Ruebner, Matthias; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Pharoah, Paul D.P.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; González-Neira, Anna; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Anton-Culver, Hoda; Neuhausen, Susan L.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Dörk, Thilo; Bogdanova, Natalia V.; Helbig, Sonja; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O.; Lambrechts, Diether; Zhao, Hui; Weltens, Caroline; van Limbergen, Erik; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Seibold, Petra; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Capra, Fabio; Couch, Fergus J.; Olson, Janet E.; Hallberg, Emily; Vachon, Celine; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; See, Mee-Hoong; Cornes, Belinda; Cheng, Ching-Yu; Ikram, M. Kamran; Kristensen, Vessela; Zheng, Wei; Halverson, Sandra L.; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W.M.; Collée, J. Margriet; Hall, Per; Li, Jingmei; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S.; Reed, Malcolm W.R.; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Shah, Mitul; Ghoussaini, Maya; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Tang, Anthony; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Olswold, Curtis; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen-Yang; Wu, Pei-Ei; Yu, Jyh-Cherng; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Pita, Guillermo; Alonso, M. Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S.; Brown, Melissa A.; Ponder, Bruce A.J.; Chenevix-Trench, Georgia; Thompson, Deborah J.; Edwards, Stacey L.; Easton, Douglas F.; Dunning, Alison M.; French, Juliet D.

    2015-01-01

    Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER+: odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21–1.27, ptrend = 5.7 × 10−44) and estrogen-receptor-negative (ER−: OR = 1.10, 95% CI = 1.05–1.15, ptrend = 3.0 × 10−4) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10−5]) and five variants composing iCHAV3 (lead rs11949391; ER+: OR = 0.90, 95% CI = 0.87–0.93, pcond = 1.4 × 10−4). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival. PMID:25529635

  7. Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1.

    PubMed

    Glubb, Dylan M; Maranian, Mel J; Michailidou, Kyriaki; Pooley, Karen A; Meyer, Kerstin B; Kar, Siddhartha; Carlebur, Saskia; O'Reilly, Martin; Betts, Joshua A; Hillman, Kristine M; Kaufmann, Susanne; Beesley, Jonathan; Canisius, Sander; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Schmidt, Marjanka K; Broeks, Annegien; Hogervorst, Frans B; van der Schoot, C Ellen; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A; Ruebner, Matthias; Ekici, Arif B; Beckmann, Matthias W; Peto, Julian; dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Pharoah, Paul D P; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Yang, Rongxi; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; González-Neira, Anna; Benitez, Javier; Zamora, M Pilar; Arias Perez, Jose Ignacio; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Ko, Yon-Dschun; Brüning, Thomas; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tanaka, Hideo; Dörk, Thilo; Bogdanova, Natalia V; Helbig, Sonja; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Wu, Anna H; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O; Lambrechts, Diether; Zhao, Hui; Weltens, Caroline; van Limbergen, Erik; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Seibold, Petra; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Capra, Fabio; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Giles, Graham G; Milne, Roger L; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; See, Mee-Hoong; Cornes, Belinda; Cheng, Ching-Yu; Ikram, M Kamran; Kristensen, Vessela; Zheng, Wei; Halverson, Sandra L; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Klevebring, Daniel; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John W M; Collée, J Margriet; Hall, Per; Li, Jingmei; Humphreys, Keith; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Shah, Mitul; Ghoussaini, Maya; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Tang, Anthony; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Olswold, Curtis; Slager, Susan; Toland, Amanda E; Yannoukakos, Drakoulis; Shen, Chen-Yang; Wu, Pei-Ei; Yu, Jyh-Cherng; Hou, Ming-Feng; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S; Brown, Melissa A; Ponder, Bruce A J; Chenevix-Trench, Georgia; Thompson, Deborah J; Edwards, Stacey L; Easton, Douglas F; Dunning, Alison M; French, Juliet D

    2015-01-08

    Genome-wide association studies (GWASs) have revealed SNP rs889312 on 5q11.2 to be associated with breast cancer risk in women of European ancestry. In an attempt to identify the biologically relevant variants, we analyzed 909 genetic variants across 5q11.2 in 103,991 breast cancer individuals and control individuals from 52 studies in the Breast Cancer Association Consortium. Multiple logistic regression analyses identified three independent risk signals: the strongest associations were with 15 correlated variants (iCHAV1), where the minor allele of the best candidate, rs62355902, associated with significantly increased risks of both estrogen-receptor-positive (ER(+): odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.21-1.27, ptrend = 5.7 × 10(-44)) and estrogen-receptor-negative (ER(-): OR = 1.10, 95% CI = 1.05-1.15, ptrend = 3.0 × 10(-4)) tumors. After adjustment for rs62355902, we found evidence of association of a further 173 variants (iCHAV2) containing three subsets with a range of effects (the strongest was rs113317823 [pcond = 1.61 × 10(-5)]) and five variants composing iCHAV3 (lead rs11949391; ER(+): OR = 0.90, 95% CI = 0.87-0.93, pcond = 1.4 × 10(-4)). Twenty-six percent of the prioritized candidate variants coincided with four putative regulatory elements that interact with the MAP3K1 promoter through chromatin looping and affect MAP3K1 promoter activity. Functional analysis indicated that the cancer risk alleles of four candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) increased MAP3K1 transcriptional activity. Chromatin immunoprecipitation analysis revealed diminished GATA3 binding to the minor (cancer-protective) allele of rs17432750, indicating a mechanism for its action. We propose that the cancer risk alleles act to increase MAP3K1 expression in vivo and might promote breast cancer cell survival.

  8. Genome-wide Regional Heritability Mapping Identifies a Locus Within the TOX2 Gene Associated With Major Depressive Disorder.

    PubMed

    Zeng, Yanni; Navarro, Pau; Shirali, Masoud; Howard, David M; Adams, Mark J; Hall, Lynsey S; Clarke, Toni-Kim; Thomson, Pippa A; Smith, Blair H; Murray, Alison; Padmanabhan, Sandosh; Hayward, Caroline; Boutin, Thibaud; MacIntyre, Donald J; Lewis, Cathryn M; Wray, Naomi R; Mehta, Divya; Penninx, Brenda W J H; Milaneschi, Yuri; Baune, Bernhard T; Air, Tracy; Hottenga, Jouke-Jan; Mbarek, Hamdi; Castelao, Enrique; Pistis, Giorgio; Schulze, Thomas G; Streit, Fabian; Forstner, Andreas J; Byrne, Enda M; Martin, Nicholas G; Breen, Gerome; Müller-Myhsok, Bertram; Lucae, Susanne; Kloiber, Stefan; Domenici, Enrico; Deary, Ian J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

    2017-09-01

    Major depressive disorder (MDD) is the second largest cause of global disease burden. It has an estimated heritability of 37%, but published genome-wide association studies have so far identified few risk loci. Haplotype-block-based regional heritability mapping (HRHM) estimates the localized genetic variance explained by common variants within haplotype blocks, integrating the effects of multiple variants, and may be more powerful for identifying MDD-associated genomic regions. We applied HRHM to Generation Scotland: The Scottish Family Health Study, a large family- and population-based Scottish cohort (N = 19,896). Single-single nucleotide polymorphism (SNP) and haplotype-based association tests were used to localize the association signal within the regions identified by HRHM. Functional prediction was used to investigate the effect of MDD-associated SNPs within the regions. A haplotype block across a 24-kb region within the TOX2 gene reached genome-wide significance in HRHM. Single-SNP- and haplotype-based association tests demonstrated that five of nine genotyped SNPs and two haplotypes within this block were significantly associated with MDD. The expression of TOX2 and a brain-specific long noncoding RNA RP1-269M15.3 in frontal cortex and nucleus accumbens basal ganglia, respectively, were significantly regulated by MDD-associated SNPs within this region. Both the regional heritability and single-SNP associations within this block were replicated in the UK-Ireland group of the most recent release of the Psychiatric Genomics Consortium (PGC), the PGC2-MDD (Major Depression Dataset). The SNP association was also replicated in a depressive symptom sample that shares some individuals with the PGC2-MDD. This study highlights the value of HRHM for MDD and provides an important target within TOX2 for further functional studies. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Admixture mapping in two Mexican samples identifies significant associations of locus ancestry with triglyceride levels in the BUD13/ZNF259/APOA5 region and fine mapping points to rs964184 as the main driver of the association signal

    PubMed Central

    Mazurek, Andrew; Sockell, Alexandra; Morris, Andrew P.; Petty, Lauren E.; Hanis, Craig L.; Cox, Nancy J.; Cruz, Miguel

    2017-01-01

    We carried out an admixture mapping study of lipid traits in two samples from Mexico City. Native American locus ancestry was significantly associated with triglyceride levels in a broad region of chromosome 11 overlapping the BUD13, ZNF259 and APOA5 genes. In our fine-mapping analysis of this region using dense genome-wide data, rs964184 is the only marker included in the 99% credible set of SNPs, providing strong support for rs964184 as the causal variant within this region. The frequency of the allele associated with increased triglyceride concentrations (rs964184-G) is between 30–40% higher in Native American populations from Mexico than in European populations. The evidence currently available for this variant indicates that it may be exerting its effect through three potential mechanisms: 1) modification of enhancer activity, 2) regulation of the expression of several genes in cis and/or trans, or 3) modification of the methylation patterns of the promoter of the APOA5 gene. PMID:28245265

  10. Admixture mapping in two Mexican samples identifies significant associations of locus ancestry with triglyceride levels in the BUD13/ZNF259/APOA5 region and fine mapping points to rs964184 as the main driver of the association signal.

    PubMed

    Parra, Esteban J; Mazurek, Andrew; Gignoux, Christopher R; Sockell, Alexandra; Agostino, Michael; Morris, Andrew P; Petty, Lauren E; Hanis, Craig L; Cox, Nancy J; Valladares-Salgado, Adan; Below, Jennifer E; Cruz, Miguel

    2017-01-01

    We carried out an admixture mapping study of lipid traits in two samples from Mexico City. Native American locus ancestry was significantly associated with triglyceride levels in a broad region of chromosome 11 overlapping the BUD13, ZNF259 and APOA5 genes. In our fine-mapping analysis of this region using dense genome-wide data, rs964184 is the only marker included in the 99% credible set of SNPs, providing strong support for rs964184 as the causal variant within this region. The frequency of the allele associated with increased triglyceride concentrations (rs964184-G) is between 30-40% higher in Native American populations from Mexico than in European populations. The evidence currently available for this variant indicates that it may be exerting its effect through three potential mechanisms: 1) modification of enhancer activity, 2) regulation of the expression of several genes in cis and/or trans, or 3) modification of the methylation patterns of the promoter of the APOA5 gene.

  11. Refined genetic mapping of autosomal dominant retinitis pigmentosa locus RP18 reduces the critical region to 2 cM between D1S442 and D1S2858 on chromosome 1q.

    PubMed

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

    1998-04-01

    Linkage analysis was performed on a large Danish family to refine the position of RP18, the locus for autosomal dominant retinitis pigmentosa, mapped previously between D1S534 and D1S305 in chromosome 1p13-q21. We genotyped the family members for five microsatellite-type DNA polymorphisms and mapped RP18 between D1S422 and D1S2858 to a region of less than 2 cM. No obvious candidate gene has yet been assigned to the chromosomal interval defined here.

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

    PubMed Central

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

    2016-01-01

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

  13. The use of metabolomic quantitative trait locus mapping and osmotic adjustment traits for the improvement of crop yields under environmental stresses.

    PubMed

    Abdelrahman, Mostafa; Burritt, David J; Tran, Lam-Son Phan

    2017-06-28

    an emphasis on the use of metabolomic quantitative trait locus mapping and osmotic adjustment agronomic traits, for the improvement of crop yields under environmental stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Genetic and physical mapping of the earliness per se locus Eps-A (m) 1 in Triticum monococcum identifies EARLY FLOWERING 3 (ELF3) as a candidate gene.

    PubMed

    Alvarez, M A; Tranquilli, G; Lewis, S; Kippes, N; Dubcovsky, J

    2016-07-01

    Wheat cultivars exposed to optimal photoperiod and vernalization treatments still exhibit differences in flowering time, referred to as earliness per se (Eps). We previously identified the Eps-A (m) 1 locus from Triticum monococcum and showed that the allele from cultivated accession DV92 significantly delays heading time and increases the number of spikelets per spike relative to the allele from wild accession G3116. Here, we expanded a high-density genetic and physical map of the Eps-A (m) 1 region and identified the wheat ortholog of circadian clock regulator EARLY FLOWERING 3 (ELF3) as a candidate gene. No differences in ELF3 transcript levels were found between near-isogenic lines carrying the DV92 and G3116 Eps-A (m) 1 alleles, but the encoded ELF3 proteins differed in four amino acids. These differences were associated with altered transcription profiles of PIF-like, PPD1, and FT1, which are known downstream targets of ELF3. Tetraploid wheat lines with combined truncation mutations in the A- and B-genome copies of ELF3 flowered earlier and had less spikelets per spike than the wild-type control under short- and long-day conditions. Both effects were stronger in a photoperiod-sensitive than in a reduced photoperiod-sensitive background, indicating a significant epistatic interaction between PPD1 and ELF3 (P < 0.0001). By contrast, the introgression of the T. monococcum chromosome segment carrying the Eps-A (m) 1 allele from DV92 into durum wheat delayed flowering and increased the number of spikelets per spike. Taken together, the above results support the hypothesis that ELF3 is Eps-A (m) 1. The ELF3 alleles identified here provide additional tools to modulate reproductive development in wheat.

  15. A new three-locus model for rootstock-induced dwarfing in apple revealed by genetic mapping of root bark percentage.

    PubMed

    Harrison, Nicola; Harrison, Richard J; Barber-Perez, Nuria; Cascant-Lopez, Emma; Cobo-Medina, Magdalena; Lipska, Marzena; Conde-Ruíz, Rebeca; Brain, Philip; Gregory, Peter J; Fernández-Fernández, Felicidad

    2016-03-01

    Rootstock-induced dwarfing of apple scions revolutionized global apple production during the twentieth century, leading to the development of modern intensive orchards. A high root bark percentage (the percentage of the whole root area constituted by root cortex) has previously been associated with rootstock-induced dwarfing in apple. In this study, the root bark percentage was measured in a full-sib family of ungrafted apple rootstocks and found to be under the control of three loci. Two quantitative trait loci (QTLs) for root bark percentage were found to co-localize to the same genomic regions on chromosome 5 and chromosome 11 previously identified as controlling dwarfing, Dw1 and Dw2, respectively. A third QTL was identified on chromosome 13 in a region that has not been previously associated with dwarfing. The development of closely linked sequence-tagged site markers improved the resolution of allelic classes, thereby allowing the detection of dominance and epistatic interactions between loci, with high root bark percentage only occurring in specific allelic combinations. In addition, we report a significant negative correlation between root bark percentage and stem diameter (an indicator of tree vigour), measured on a clonally propagated grafted subset of the mapping population. The demonstrated link between root bark percentage and rootstock-induced dwarfing of the scion leads us to propose a three-locus model that is able to explain levels of dwarfing from the dwarf 'M.27' to the semi-invigorating rootstock 'M.116'. Moreover, we suggest that the QTL on chromosome 13 (Rb3) might be analogous to a third dwarfing QTL, Dw3, which has not previously been identified.

  16. A new three-locus model for rootstock-induced dwarfing in apple revealed by genetic mapping of root bark percentage

    PubMed Central

    Harrison, Nicola; Harrison, Richard J.; Barber-Perez, Nuria; Cascant-Lopez, Emma; Cobo-Medina, Magdalena; Lipska, Marzena; Conde-Ruíz, Rebeca; Brain, Philip; Gregory, Peter J.; Fernández-Fernández, Felicidad

    2016-01-01

    Rootstock-induced dwarfing of apple scions revolutionized global apple production during the twentieth century, leading to the development of modern intensive orchards. A high root bark percentage (the percentage of the whole root area constituted by root cortex) has previously been associated with rootstock-induced dwarfing in apple. In this study, the root bark percentage was measured in a full-sib family of ungrafted apple rootstocks and found to be under the control of three loci. Two quantitative trait loci (QTLs) for root bark percentage were found to co-localize to the same genomic regions on chromosome 5 and chromosome 11 previously identified as controlling dwarfing, Dw1 and Dw2, respectively. A third QTL was identified on chromosome 13 in a region that has not been previously associated with dwarfing. The development of closely linked sequence-tagged site markers improved the resolution of allelic classes, thereby allowing the detection of dominance and epistatic interactions between loci, with high root bark percentage only occurring in specific allelic combinations. In addition, we report a significant negative correlation between root bark percentage and stem diameter (an indicator of tree vigour), measured on a clonally propagated grafted subset of the mapping population. The demonstrated link between root bark percentage and rootstock-induced dwarfing of the scion leads us to propose a three-locus model that is able to explain levels of dwarfing from the dwarf ‘M.27’ to the semi-invigorating rootstock ‘M.116’. Moreover, we suggest that the QTL on chromosome 13 (Rb3) might be analogous to a third dwarfing QTL, Dw3, which has not previously been identified. PMID:26826217

  17. An autosomal dominant locus, Nka, mapping to the Ly-49 region of a rat natural killer (NK) gene complex, controls NK cell lysis of allogeneic lymphocytes

    PubMed Central

    1996-01-01

    Natural Killer (NK) cells can recognize and kill MHC-incompatible normal bone marrow-derived cells. Presently characterized MHC-binding receptors on NK cells, including the Ly-49 family in the mouse, transmit inhibitory signals upon binding to cognate class I MHC ligands. Here we study in vivo NK-mediated lysis of normal allogeneic lymphocytes in crosses between alloreactivity-competent PVG rats and alloreactivity-deficient DA rats. NK cells from both strains are able to lyse standard tumor targets. We identify an autosomal dominant locus, Nka, that controls NK-mediated alloreactivity. Individuals carrying the dominant PVG allele in single dose were fully competent in eliminating allogeneic target cells, suggesting that Nka encodes or regulates a gene product inducing or activating alloreactivity. By linkage analysis and pulsed field gel electrophoresis, a natural killer gene complex (NKC) on rat chromosome 4 is described that contains the rat NKR-P1 and Ly-49 multigene families plus a rat NKG2D homologue. Nka maps within the NKC, together with the most telomeric Ly-49 family members, but separate from NKG2D and the NKR-P1 family. The Nka-encoded response, moreover, correlates with the expression of transcripts for Ly-49 receptors in NK cell populations, as Northern blot analysis demonstrated low expression of Ly-49 genes in DA NK cells, in contrast to high expression in alloreactivity-competent PVG, (DA X PVG)F1, and PVG.1AVI NK cells. The low Ly-49 expression in DA is not induced by MHC haplotype, as demonstrated by high expression of Ly-49 in the DA MHC- congenic PVG.1AVI strain. Finally, we have cloned and characterized the first four members of the rat Ly-49 gene family. Their cytoplasmic domains demonstrate substantial heterogeneity, consistent with the hypothesis that different Ly-49 family members may subserve different signaling functions. PMID:8642329

  18. Linkage and association mapping of a chromosome 1q21-q24 type 2 diabetes susceptibility locus in northern European Caucasians.

    PubMed

    Das, Swapan Kumar; Hasstedt, Sandra J; Zhang, Zhengxian; Elbein, Steven C

    2004-02-01

    We have identified a region on chromosome 1q21-q24 that was significantly linked to type 2 diabetes in multiplex families of Northern European ancestry and also in Pima Indians, Amish families, and families from France and England. We sought to narrow and map this locus using a combination of linkage and association approaches by typing microsatellite markers at 1.2 and 0.5 cM densities, respectively, over a region of 37 cM (23.5 Mb). We tested linkage by parametric and nonparametric approaches and association using both case-control and family-based methods. In the 40 multiplex families that provided the previous evidence for linkage, the highest parametric, recessive logarithm of odds (LOD) score was 5.29 at marker D1S484 (168.5 cM, 157.5 Mb) without heterogeneity. Nonparametric linkage (NPL) statistics (P = 0.00009), SimWalk2 Statistic A (P = 0.0002), and sib-pair analyses (maximum likelihood score = 6.07) all mapped to the same location. The one LOD CI was narrowed to 156.8-158.9 Mb. Under recessive, two-point linkage analysis, adjacent markers D1S2675 (171.5 cM, 158.9 Mb) and D1S1679 (172 cM, 159.1 Mb) showed LOD scores >3.0. Nonparametric analyses revealed a second linkage peak at 180 cM near marker D1S1158 (163.3 Mb, NPL score 3.88, P = 0.0001), which was also supported by case-control (marker D1S194, 178 cM, 162.1 Mb; P = 0.003) and family-based (marker ATA38A05, 179 cM, 162.5 Mb; P = 0.002) association studies. We propose that the replicated linkage findings actually encompass at least two closely spaced regions, with a second susceptibility region located telomeric at 162.5-164.7 Mb.

  19. 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.

  20. Fine-Mapping the Wheat Snn1 Locus Conferring Sensitivity to the Parastagonospora nodorum Necrotrophic Effector SnTox1 Using an Eight Founder Multiparent Advanced Generation Inter-Cross Population.

    PubMed

    Cockram, James; Scuderi, Alice; Barber, Toby; Furuki, Eiko; Gardner, Keith A; Gosman, Nick; Kowalczyk, Radoslaw; Phan, Huyen P; Rose, Gemma A; Tan, Kar-Chun; Oliver, Richard P; Mackay, Ian J

    2015-09-28

    The necrotrophic fungus Parastagonospora nodorum is an important pathogen of one of the world's most economically important cereal crops, wheat (Triticum aestivum L.). P. nodorum produces necrotrophic protein effectors that mediate host cell death, providing nutrients for continuation of the infection process. The recent discovery of pathogen effectors has revolutionized disease resistance breeding for necrotrophic diseases in crop species, allowing often complex genetic resistance mechanisms to be broken down into constituent parts. To date, three effectors have been identified in P. nodorum. Here we use the effector, SnTox1, to screen 642 progeny from an eight-parent multiparent advanced generation inter-cross (i.e., MAGIC) population, genotyped with a 90,000-feature single-nucleotide polymorphism array. The MAGIC founders showed a range of sensitivity to SnTox1, with transgressive segregation evident in the progeny. SnTox1 sensitivity showed high heritability, with quantitative trait locus analyses fine-mapping the Snn1 locus to the short arm of chromosome 1B. In addition, a previously undescribed SnTox1 sensitivity locus was identified on the long arm of chromosome 5A, termed here QSnn.niab-5A.1. The peak single-nucleotide polymorphism for the Snn1 locus was converted to the KASP genotyping platform, providing breeders and researchers a simple and cheap diagnostic marker for allelic state at Snn1.

  1. Fine-Mapping the Wheat Snn1 Locus Conferring Sensitivity to the Parastagonospora nodorum Necrotrophic Effector SnTox1 Using an Eight Founder Multiparent Advanced Generation Inter-Cross Population

    PubMed Central

    Cockram, James; Scuderi, Alice; Barber, Toby; Furuki, Eiko; Gardner, Keith A.; Gosman, Nick; Kowalczyk, Radoslaw; Phan, Huyen P.; Rose, Gemma A.; Tan, Kar-Chun; Oliver, Richard P.; Mackay, Ian J.

    2015-01-01

    The necrotrophic fungus Parastagonospora nodorum is an important pathogen of one of the world’s most economically important cereal crops, wheat (Triticum aestivum L.). P. nodorum produces necrotrophic protein effectors that mediate host cell death, providing nutrients for continuation of the infection process. The recent discovery of pathogen effectors has revolutionized disease resistance breeding for necrotrophic diseases in crop species, allowing often complex genetic resistance mechanisms to be broken down into constituent parts. To date, three effectors have been identified in P. nodorum. Here we use the effector, SnTox1, to screen 642 progeny from an eight-parent multiparent advanced generation inter-cross (i.e., MAGIC) population, genotyped with a 90,000-feature single-nucleotide polymorphism array. The MAGIC founders showed a range of sensitivity to SnTox1, with transgressive segregation evident in the progeny. SnTox1 sensitivity showed high heritability, with quantitative trait locus analyses fine-mapping the Snn1 locus to the short arm of chromosome 1B. In addition, a previously undescribed SnTox1 sensitivity locus was identified on the long arm of chromosome 5A, termed here QSnn.niab-5A.1. The peak single-nucleotide polymorphism for the Snn1 locus was converted to the KASP genotyping platform, providing breeders and researchers a simple and cheap diagnostic marker for allelic state at Snn1. PMID:26416667

  2. 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.

  3. Genetic heterogeneity among craniosynostosis syndromes: Mapping the Saethre-Chotzen syndrome locus between D7S513 and D7S516 and exclusion of Jackson-Weiss and Crouzon syndrome loci from 7p

    SciTech Connect

    Lewanda, A.F.; Taylor, E.W.; Li, Xiang; Beloff, M. ); Cohen, M.M. Jr. ); Jackson, C.E. ); Day, D. ); Clarren, S.K. ); Ortiz, R.; Garcia, C. )

    1994-01-01

    Saethre-Chotzen, Crouzon, and Jackson-Weiss syndromes are craniosynostotic autosomal dominant conditions with a wide variability in expression. Saethre-Chotzen has been mapped to chromosome 7p by L. A. Brueton et al., the Greig cephalopolysyndactyly gene was identified at 7p13 by A. Vortkamp et al., and many cases of craniosynostosis have been associated with 7p deletions. The authors confirmed linkage of the Saethre-Chotzen syndrome locus to chromosome 7p. The tightest linkage was to locus D7S493 (7 = 5.04, [theta] = 0.00), and linkage and haplotype analyses refined the location of the gene to the region between D7S513 and D7S516. Jackson-Weiss and Crouzon syndrome loci were analyzed using markers spanning the entire 7p arm and were excluded, proving that they are nonallelic to Saethre-Chotzen, Greig cephalopolysyndactyly, and the del(7p) syndromes. 29 refs., 1 fig., 2 tabs.

  4. Construction of a high-density genetic map by specific locus amplified fragment sequencing (SLAF-seq) and its application to Quantitative Trait Loci (QTL) analysis for boll weight in upland cotton (Gossypium hirsutum.).

    PubMed

    Zhang, Zhen; Shang, Haihong; Shi, Yuzhen; Huang, Long; Li, Junwen; Ge, Qun; Gong, Juwu; Liu, Aiying; Chen, Tingting; Wang, Dan; Wang, Yanling; Palanga, Koffi Kibalou; Muhammad, Jamshed; Li, Weijie; Lu, Quanwei; Deng, Xiaoying; Tan, Yunna; Song, Weiwu; Cai, Juan; Li, Pengtao; Rashid, Harun or; Gong, Wankui; Yuan, Youlu

    2016-04-11

    Upland Cotton (Gossypium hirsutum) is one of the most important worldwide crops it provides natural high-quality fiber for the industrial production and everyday use. Next-generation sequencing is a powerful method to identify single nucleotide polymorphism markers on a large scale for the construction of a high-density genetic map for quantitative trait loci mapping. In this research, a recombinant inbred lines population developed from two upland cotton cultivars 0-153 and sGK9708 was used to construct a high-density genetic map through the specific locus amplified fragment sequencing method. The high-density genetic map harbored 5521 single nucleotide polymorphism markers which covered a total distance of 3259.37 cM with an average marker interval of 0.78 cM without gaps larger than 10 cM. In total 18 quantitative trait loci of boll weight were identified as stable quantitative trait loci and were detected in at least three out of 11 environments and explained 4.15-16.70 % of the observed phenotypic variation. In total, 344 candidate genes were identified within the confidence intervals of these stable quantitative trait loci based on the cotton genome sequence. These genes were categorized based on their function through gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and eukaryotic orthologous groups analysis. This research reported the first high-density genetic map for Upland Cotton (Gossypium hirsutum) with a recombinant inbred line population using single nucleotide polymorphism markers developed by specific locus amplified fragment sequencing. We also identified quantitative trait loci of boll weight across 11 environments and identified candidate genes within the quantitative trait loci confidence intervals. The results of this research would provide useful information for the next-step work including fine mapping, gene functional analysis, pyramiding breeding of functional genes as well as marker-assisted selection.

  5. Allelism analysis of BrRfp locus in different restorer lines and map-based cloning of a fertility restorer gene, BrRfp1, for pol CMS in Chinese cabbage (Brassica rapa L.).

    PubMed

    Zhang, Huamin; Wu, Junqing; Dai, Zihui; Qin, Meiling; Hao, Lingyu; Ren, Yanjing; Li, Qingfei; Zhang, Lugang

    2017-03-01

    In Chinese cabbage, there are two Rf loci for pol CMS and one of them was mapped to a 12.6-kb region containing a potential candidate gene encoding PPR protein. In Chinese cabbage (Brassica rapa), polima cytoplasmic male sterility (pol CMS) is an important CMS type and is widely used for hybrid breeding. By extensive test crossing in Chinese cabbage, four restorer lines (92s105, 01s325, 00s109, and 88s148) for pol CMS were screened. By analyzing the allelism of the four restorer lines, it was found that 92s105, 01s325, and 00s109 had the same "restorers of fertility" (Rf) locus (designated as BrRfp1), but 88s148 had a different Rf locus (designated as BrRfp2). For fine mapping the BrRfp1 locus of 92s105, a BC1F1 population with 487 individuals and a BC1F2 population with 2485 individuals were successively constructed. Using simple sequence repeat (SSR) markers developed from Brassica rapa reference genome and InDel markers derived from whole-genome resequencing data of 94c9 and 92s105, BrRfp1 was mapped to a 12.6-kb region containing a potential candidate gene encoding pentatricopeptide repeat-containing protein. Based on the nucleotide polymorphisms of the candidate gene sequence between the restoring and nonrestoring alleles, a co-segregating marker SC718 was developed, which would be helpful for hybrid breeding by marker-assisted screening and for detecting new restorer lines.

  6. Congenic mapping of the type 1 diabetes locus, Idd3, to a 780-kb region of mouse chromosome 3: identification of a candidate segment of ancestral DNA by haplotype mapping.

    PubMed

    Lyons, P A; Armitage, N; Argentina, F; Denny, P; Hill, N J; Lord, C J; Wilusz, M B; Peterson, L B; Wicker, L S; Todd, J A

    2000-04-01

    Type 1 diabetes in the nonobese diabetic (NOD) mouse arises as a consequence of T cell-mediated destruction of the insulin-producing beta cells of the pancreas. Although little is known of the events that initiate and subsequently drive beta-cell destruction it is clear that the entire process is under complex genetic control. At present 19 loci have been mapped that influence the development of diabetes either at the level of initiation of insulitis or at the level of progression from insulitis to overt diabetes, or both. Previously, we have mapped one of these loci, Idd3, to a 0.35-cM interval on proximal mouse chromosome 3. In the present study we have narrowed the map position of this locus to an interval of 0.15 cM by a combination of novel congenic strains and an ancestral haplotype analysis approach. We have constructed a physical contig in bacterial artificial chromosome (BAC) clones across the minimal interval. Restriction mapping of the BAC contig placed the maximum size of the Idd3 interval at 780 kb between the markers D3Nds36 and D3Nds76. To refine further the Idd3 interval we developed a series of novel single nucleotide polymorphisms (SNPs) and carried out haplotype analysis on DNA from mouse strains known to carry either Idd3 susceptibility or protective alleles. This haplotype analysis identified a 145-kb segment of ancestral DNA between the microsatellite marker D3Nds6 and the SNP 81.3. One haplotype of this ancestral segment of DNA is found in mouse strains carrying an Idd3 susceptibility allele and another is found in mouse strains carrying an Idd3 protective allelle. Within the 780-kb congenically defined interval this 145-kb segment represents the most likely location for Idd3. The Il2 gene, which encodes the cytokine interleukin 2 (IL2), maps to this interval and is a strong candidate for Idd3. To investigate whether sequence variation exists in the promoter region of the Il2 gene, which might alter its expression, we sequenced the promoter

  7. Heritability of the maternal meiotic drive system linked to Om and high-resolution mapping of the Responder locus in mouse.

    PubMed Central

    Pardo-Manuel De Villena, F; de La Casa-Esperón, E; Williams, J W; Malette, J M; Rosa, M; Sapienza, C

    2000-01-01

    Matings between (C57BL/6 x DDK)F(1) females and C57BL/6 males result in a significant excess of offspring inheriting maternal DDK alleles in the central region of mouse chromosome 11 due to meiotic drive at the second meiotic division. We have shown previously that the locus subject to selection is in the vicinity of D11Mit66, a marker closely linked to the Om locus that controls the preimplantation embryo-lethal phenotype known as the "DDK syndrome." We have also shown that observation of meiotic drive in this system depends upon the genotype of the sire. Here we show that females that are heterozygous at Om retain the meiotic drive phenotype and define a 0.32-cM candidate interval for the Responder locus in this drive system. In addition, analysis of the inheritance of alleles at Om among the offspring of F(1) intercrosses indicates that the effect of the sire is determined by the sperm genotype at Om or a locus linked to Om. PMID:10790402

  8. A Novel Multivariate Approach to Phenotyping and Association Mapping of Multi-Locus Gametophytic Self-Incompatibility Reveals S, Z, and Other Loci in a Perennial Ryegrass (Poaceae) Population

    PubMed Central

    Thorogood, Daniel; Yates, Steven; Manzanares, Chloé; Skot, Leif; Hegarty, Matthew; Blackmore, Tina; Barth, Susanne; Studer, Bruno

    2017-01-01

    Self-incompatibility (SI) is a mechanism that many flowering plants employ to prevent fertilisation by self- and self-like pollen ensuring heterozygosity and hybrid vigour. Although a number of single locus mechanisms have been characterised in detail, no multi-locus systems have been fully elucidated. Historically, examples of the genetic analysis of multi-locus SI, to make analysis tractable, are either made on the progeny of bi-parental crosses, where the number of alleles at each locus is restricted, or on crosses prepared in such a way that only one of the SI loci segregates. Perennial ryegrass (Lolium perenne L.) possesses a well-documented two locus (S and Z) gametophytic incompatibility system. A more universal, realistic proof of principle study was conducted in a perennial ryegrass population in which allelic and non-allelic diversity was not artificially restricted. A complex pattern of pollinations from a diallel cross was revealed which could not possibly be interpreted easily per se, even with an already established genetic model. Instead, pollination scores were distilled into principal component scores described as Compatibility Components (CC1-CC3). These were then subjected to a conventional genome-wide association analysis. CC1 associated with markers on linkage groups (LGs) 1, 2, 3, and 6, CC2 exclusively with markers in a genomic region on LG 2, and CC3 with markers on LG 1. BLAST alignment with the Brachypodium physical map revealed highly significantly associated markers with peak associations with genes adjacent and four genes away from the chromosomal locations of candidate SI genes, S- and Z-DUF247, respectively. Further significant associations were found in a Brachypodium distachyon chromosome 3 region, having shared synteny with Lolium LG 1, suggesting further SI loci linked to S or extensive micro-re-arrangement of the genome between B. distachyon and L. perenne. Significant associations with gene sequences aligning with marker

  9. Linkage analyses in Darier disease (DD) and Halley-Halley disease (HHD): Fine mapping of the DD locus on chromosome 12q and rejection of the hypothesis that HHD is allelic to DD

    SciTech Connect

    Richard, G.; Wright, A.R.; Compton, J.G.

    1994-09-01

    DD and HHD are rare autosomal dominant genodermatoses. These disorders of cornification share some clinical and histologic features and for many years were thought to be variants of the same disease. DD presents as hyperkeratotic papules and plaques, usually in a seborrheic distribution; rarely, blisters can occur. Mucous membranes and nails may also be involved. Skin involvement in HHD includes erythematous and scaly plaques, and vesicular or crusted lesions, often in intertriginous areas. Both diseases have age-dependent penetrance and are characterized histologically by a focal loss of cell adhesion in the suprabasal epidermis leading to lacunaes (acantholysis) and premature keratinization (dyskeratosis). We analyzed linkage of DD in ten families with markers in 12q23-q24.1, the region to which it has been mapped. Detailed genotype analysis of recombinant chromosomes in our families, along with previously reported data, refine the location of the DD gene to about a 4 cM interval flanked by the loci D12S129 and D12S105. We have excluded two genes in 12q22-q24, PLA2A and PAH, as candidate loci for DD. Three other gene loci (PPP1C, PMCH and PMCA1) mapping in 12q21-q24, remain potential candidates. The region containing the DD gene is an obvious candidate location to test for HHD. We investigated four multigeneration families with HHD for linkage to the DD gene locus using several tightly linked microsatellite markers. Obligate recombination with each marker tested was observed, and the HHD locus was excluded from about 37 cM around the DD locus, proving that DD and HHD are not allelic disorders.

  10. The wheat Phs-A1 pre-harvest sprouting resistance locus delays the rate of seed dormancy loss and maps 0.3 cM distal to the PM19 genes in UK germplasm

    PubMed Central

    Shorinola, Oluwaseyi; Bird, Nicholas; Simmonds, James; Berry, Simon; Henriksson, Tina; Jack, Peter; Werner, Peter; Gerjets, Tanja; Scholefield, Duncan; Balcárková, Barbara; Valárik, Miroslav; Holdsworth, M. J.; Flintham, John; Uauy, Cristobal

    2016-01-01

    The precocious germination of cereal grains before harvest, also known as pre-harvest sprouting, is an important source of yield and quality loss in cereal production. Pre-harvest sprouting is a complex grain defect and is becoming an increasing challenge due to changing climate patterns. Resistance to sprouting is multi-genic, although a significant proportion of the sprouting variation in modern wheat cultivars is controlled by a few major quantitative trait loci, including Phs-A1 in chromosome arm 4AL. Despite its importance, little is known about the physiological basis and the gene(s) underlying this important locus. In this study, we characterized Phs-A1 and show that it confers resistance to sprouting damage by affecting the rate of dormancy loss during dry seed after-ripening. We show Phs-A1 to be effective even when seeds develop at low temperature (13 °C). Comparative analysis of syntenic Phs-A1 intervals in wheat and Brachypodium uncovered ten orthologous genes, including the Plasma Membrane 19 genes (PM19-A1 and PM19-A2) previously proposed as the main candidates for this locus. However, high-resolution fine-mapping in two bi-parental UK mapping populations delimited Phs-A1 to an interval 0.3 cM distal to the PM19 genes. This study suggests the possibility that more than one causal gene underlies this major pre-harvest sprouting locus. The information and resources reported in this study will help test this hypothesis across a wider set of germplasm and will be of importance for breeding more sprouting resilient wheat varieties. PMID:27217549

  11. Mapping of a locus correcting lack of phosphoribosylaminoimidazole carboxylase activity in Chinese hamster ovary cell Ade-D mutants to human chromosome 4.

    PubMed

    Barton, J W; Hart, I M; Patterson, D

    1991-02-01

    The human phosphoribosylaminoimidazole (AIR) carboxylase locus has been until this report one of the genes encoding purine biosynthetic enzymes that had not been assigned to an individual human chromosome. Characterization of Chinese hamster ovary (CHO) cell mutant Ade-D showed that the cell line was unable to produce IMP and accumulated AIR. CHO Ade-D cells were fused with normal human lymphocytes utilizing inactivated Sendai virus and the resulting hybrid cell lines were selected for purine prototrophy. Cytogenetic analysis showed a 100% concordance value for chromosome 4. Two of the isolated subclones contained only the long arm of chromosome 4 translocated onto a CHO chromosome, providing evidence for a regional assignment of the Ade-D gene to the long arm of chromosome 4. Two of the subclones containing chromosome 4 were subjected to the BrdU visible light segregation. All of the isolated purine auxotrophic cell lines showed a loss of the q arm of chromosome 4. The localization of the Ade-D locus to the long arm of chromosome 4 may reveal further clustering of the mammalian purine genes since the Ade-A locus has previously been regionally assigned to 4pter-q21.

  12. 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.

  13. Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse

    PubMed Central

    2012-01-01

    Background Adrenal gland of mice contains a transient zone between the adrenal cortex and the adrenal medulla: the X-zone. There are clear strain differences in terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain develop adrenal X-zones containing exclusively vacuolated cells, whereas females of the inbred mouse B6 strain develop X-zones containing only non-vacuolated cells. The X-zone vacuolation is a physiologic process associated with the X-zone degeneration and is tightly regulated by genetic factors. Identification of the genetic factors controlling such strain differences should help analyze the X-zone function. In this study, a quantitative trait locus (QTL) analysis for the extent of X-zone vacuolation was performed for two types of F2 female mice: F2Ay mice (F2 mice with the Ay allele) and F2 non-Ay mice (F2 mice without the Ay allele). These were produced by crossing B6 females and DDD.Cg-Ay males. DDD.Cg-Ay is a congenic mouse strain for the Ay allele at the agouti locus and is used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested. The Ay allele is dominant and homozygous lethal; therefore, living Ay mice are invariably heterozygotes. Results Single QTL scans identified significant QTLs on chromosomes 1, 2, 6, and X for F2 non-Ay mice, and on chromosomes 2, 6, and 12 for F2Ay mice. The QTL on chromosome 2 was considered to be because of the agouti locus, which has been suggested to be associated with X-zone vacuolation. A significant QTL that interacted with the agouti locus was identified on chromosome 8. Conclusions The extent of X-zone vacuolation in DDD females was controlled by multiple genes with complex interactions. The murine X-zone is considered analogous structure to the human fetal zone. Therefore, the results of this study will aid in understanding function of not only of the X-zone but also of the human fetal zone. Identifying the genes

  14. Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse.

    PubMed

    Suto, Jun-Ichi

    2012-11-06

    Adrenal gland of mice contains a transient zone between the adrenal cortex and the adrenal medulla: the X-zone. There are clear strain differences in terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain develop adrenal X-zones containing exclusively vacuolated cells, whereas females of the inbred mouse B6 strain develop X-zones containing only non-vacuolated cells. The X-zone vacuolation is a physiologic process associated with the X-zone degeneration and is tightly regulated by genetic factors. Identification of the genetic factors controlling such strain differences should help analyze the X-zone function. In this study, a quantitative trait locus (QTL) analysis for the extent of X-zone vacuolation was performed for two types of F2 female mice: F2Ay mice (F2 mice with the Ay allele) and F2 non-Ay mice (F2 mice without the Ay allele). These were produced by crossing B6 females and DDD.Cg-Ay males. DDD.Cg-Ay is a congenic mouse strain for the Ay allele at the agouti locus and is used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested. The Ay allele is dominant and homozygous lethal; therefore, living Ay mice are invariably heterozygotes. Single QTL scans identified significant QTLs on chromosomes 1, 2, 6, and X for F2 non-Ay mice, and on chromosomes 2, 6, and 12 for F2Ay mice. The QTL on chromosome 2 was considered to be because of the agouti locus, which has been suggested to be associated with X-zone vacuolation. A significant QTL that interacted with the agouti locus was identified on chromosome 8. The extent of X-zone vacuolation in DDD females was controlled by multiple genes with complex interactions. The murine X-zone is considered analogous structure to the human fetal zone. Therefore, the results of this study will aid in understanding function of not only of the X-zone but also of the human fetal zone. Identifying the genes responsible for the QTLs will be

  15. Fine mapping and genetic association analysis of Net2, the causative D-genome locus of low temperature-induced hybrid necrosis in interspecific crosses between tetraploid wheat and Aegilops tauschii.

    PubMed

    Sakaguchi, Kouhei; Nishijima, Ryo; Iehisa, Julio Cesar Masaru; Takumi, Shigeo

    2016-10-01

    Hybrid necrosis has been observed in many interspecific hybrids from crosses between tetraploid wheat and the wheat D-genome donor Aegilops tauschii. Type II necrosis is a kind of hybrid incompatibility that is specifically characterized by low-temperature induction and growth suppression. Two complementary genes, Net1 on the AB genome and Net2 on the D genome, putatively control type II necrosis in ABD triploids and synthetic hexaploid wheat. Toward map-based cloning of Net2, a fine map around the Net2 region on 2DS was constructed in this study. Using the draft genome sequence of Ae. tauschii and the physical map of the barley genome, the Net2 locus was mapped within a 0.6 cM interval between two closely linked markers. Although local chromosomal rearrangements were observed in the Net2-corresponding region between the barley/Brachypodium and Ae. tauschii genomes, the two closely linked markers were significantly associated with type II necrosis in Ae. tauschii. These results suggest that these markers will aid efficient selection of Net2 non-carrier individuals from the Ae. tauschii population and intraspecific progeny, and could help with introgression of agriculturally important genes from Ae. tauschii to common wheat.

  16. QTL mapping identifies a major locus for resistance in wheat to Sunn pest (Eurygaster integriceps) feeding at the vegetative growth stage.

    PubMed

    Emebiri, L C; Tan, M-K; El-Bouhssini, M; Wildman, O; Jighly, A; Tadesse, W; Ogbonnaya, F C

    2017-02-01

    This research provides the first report of a major locus controlling wheat resistance to Sunn pest. It developed and validated SNP markers that will be useful for marker-assisted selection. Sunn pest (Eurygaster integriceps Puton) is the most destructive insect pest of bread wheat and durum wheat in West and Central Asia and East Europe. Breeding for resistance at the vegetative stage of growth is vital in reducing the damage caused by overwintered adult populations that feed on shoot and leaves of seedlings, and in reducing the next generation of pest populations (nymphs and adults), which can cause damage to grain quality by feeding on spikes. In the present study, two doubled haploid (DH) populations involving resistant landraces from Afghanistan were genotyped with the 90k SNP iSelect assay and candidate gene-based KASP markers. The DH lines and parents were phenotyped for resistance to Sunn pest feeding, using artificial infestation cages at Terbol station, in Lebanon, over three years. Quantitative trait locus (QTL) analysis identified a single major locus on chromosome 4BS in the two populations, with the resistance allele derived from the landrace accessions, IG139431 and IG139883. The QTL explained a maximum of 42 % of the phenotypic variation in the Cham6 × IG139431 and 56 % in the Cham6 × IG139883 populations. SNP markers closest to the QTL showed high similarity to rice genes that putatively encode proteins for defense response to herbivory and wounding. The markers were validated in a large, unrelated population of parental wheat genotypes. All wheat lines carrying the 'C-G' haplotype at the identified SNPs were resistant, suggesting that selection based on a haplotype of favourable alleles would be effective in predicting resistance status of unknown genotypes.

  17. Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2.

    PubMed

    Hawthorne, Felicia; Feng, Sheng; Metlapally, Ravikanth; Li, Yi-Ju; Tran-Viet, Khanh-Nhat; Guggenheim, Jeremy A; Malecaze, Francois; Calvas, Patrick; Rosenberg, Thomas; Mackey, David A; Venturini, Cristina; Hysi, Pirro G; Hammond, Christopher J; Young, Terri L

    2013-03-21

    Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, MYP3, has been reported on chromosome 12q21-23 by four independent linkage studies. We performed a genetic association study of the MYP3 locus in a family-based high-grade myopia cohort (n = 82) by genotyping 768 single-nucleotide polymorphisms (SNPs) within the linkage region. Qualitative testing for high-grade myopia (sphere ≤ -5 D affected, > -0.5 D unaffected) and quantitative testing on the average dioptric sphere were performed. Several genetic markers were nominally significantly associated with high-grade myopia in qualitative testing, including rs3803036, a missense mutation in PTPRR (P = 9.1 × 10(-4)) and rs4764971, an intronic SNP in UHRF1BP1L (P = 6.1 × 10(-4)). Quantitative testing determined statistically significant SNPs rs4764971, also found by qualitative testing (P = 3.1 × 10(-6)); rs7134216, in the 3' untranslated region (UTR) of DEPDC4 (P = 5.4 × 10(-7)); and rs17306116, an intronic SNP within PPFIA2 (P < 9 × 10(-4)). Independently conducted whole genome expression array analyses identified protein tyrosine phosphatase genes PTPRR and PPFIA2, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR). In an independent high-grade myopia cohort, an intronic SNP in UHRF1BP1L, rs4764971, was validated for quantitative association, and SNPs within PTPRR (quantitative) and PPFIA2 (qualitative and quantitative) approached significance. Three genes identified by our association study and supported by ocular expression and/or replication, UHRF1BP1L, PTPRR, and PPFIA2, are novel candidates for myopic development within the MYP3 locus that should be further studied.

  18. Application of Genotyping-By-Sequencing for selection of locus-specific BAC clones to construct physical maps and identify candidate genes in Vitis

    USDA-ARS?s Scientific Manuscript database

    While genotyping-by-sequencing (GBS) is widely used for linkage and association mapping, its potential for physical mapping and candidate gene identification in under-characterized species has not been fully realized. Eight half-sib Vitis families (480 progeny) were genotyped using GBS and phenotyp...

  19. 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

  20. Fine-structure mapping of the firA gene, a locus involved in the phenotypic expression of rifampin resistance in Escherichia.

    PubMed Central

    Lathe, R

    1977-01-01

    The firA (Ts)200 mutation not only eliminates the resistance to rifampin of certain genetically resistant strains, but, moreover, renders ribonucleic acid synthesis thermolabile. The firA gene has been mapped by P1 tranduction and is located extremely close to the structural gene for deoxyribonucleic acid polymerase III at 4 min on the Escherichia coli linkage map. PMID:330494

  1. Fine-structure mapping of the firA gene, a locus involved in the phenotypic expression of rifampin resistance in Escherichia.

    PubMed

    Lathe, R

    1977-09-01

    The firA (Ts)200 mutation not only eliminates the resistance to rifampin of certain genetically resistant strains, but, moreover, renders ribonucleic acid synthesis thermolabile. The firA gene has been mapped by P1 tranduction and is located extremely close to the structural gene for deoxyribonucleic acid polymerase III at 4 min on the Escherichia coli linkage map.

  2. Mapping a blood pressure quantitative trait locus to a 5.7-cM region in Dahl salt-sensitive rats.

    PubMed

    Dutil, J; Deng, A Y

    2001-05-01

    A region on rat Chromosome (Chr) 2 of the Dahl salt-sensitive rat (S) was shown previously to contain a quantitative trait locus (QTL) for blood pressure (BP). This was achieved first by linkage, followed by the use of congenic strains. A congenic strain, designated S.MNS-D2Mit6/Adh, contained a segment of Chr 2 from the Milan Normotensive (MNS) rat in the S genetic background. Since the region containing the QTL was roughly 80 cM in size, a further reduction was needed towards the positional or candidate gene cloning. Currently, two congenic substrains were made from the original strain S.MNS-D2Mit6/Adh. One of these two substrains showed a BP-lowering effect, whereas the other substrain did not. Deducing the segment not shared in the two substrains, the BP QTL has to be present in a chromosome region of roughly 5.7 cM between the marker D2Rat303 and the locus for the neutroendopeptidase gene (Nep). Nep is not included within the segment. This region does not seem to contain any candidate genes well known for the BP control. Thus, the final identification of the QTL will most likely lead to the discovery of a brand new gene for the BP regulation.

  3. Family-Based Analysis Using a Dense Single-Nucleotide Polymorphism–Based Map Defines Genetic Variation at PSORS1, the Major Psoriasis-Susceptibility Locus

    PubMed Central

    Veal, Colin D.; Capon, Francesca; Allen, Michael H.; Heath, Emma K.; Evans, Julie C.; Jones, Andrew; Patel, Shanta; Burden, David; Tillman, David; Barker, Jonathan N. W. N.; Trembath, Richard C.

    2002-01-01

    Psoriasis is a common skin disorder of multifactorial origin. Genomewide scans for disease susceptibility have repeatedly demonstrated the existence of a major locus, PSORS1 (psoriasis susceptibility 1), contained within the major histocompatibility complex (MHC), on chromosome 6p21. Subsequent refinement studies have highlighted linkage disequilibrium (LD) with psoriasis, along a 150-kb segment that includes at least three candidate genes (encoding human leukocyte antigen–C [HLA-C], α-helix–coiled-coil–rod homologue, and corneodesmosin), each of which has been shown to harbor disease-associated alleles. However, the boundaries of the minimal PSORS1 region remain poorly defined. Moreover, interpretations of allelic association with psoriasis are compounded by limited insight of LD conservation within MHC class I interval. To address these issues, we have pursued a high-resolution genetic characterization of the PSORS1 locus. We resequenced genomic segments along a 220-kb region at chromosome 6p21 and identified a total of 119 high-frequency SNPs. Using 59 SNPs (18 coding and 41 noncoding SNPs) whose position was representative of the overall marker distribution, we genotyped a data set of 171 independently ascertained parent–affected offspring trios. Family-based association analysis of this cohort highlighted two SNPs (n.7 and n.9) respectively lying 7 and 4 kb proximal to HLA-C. These markers generated highly significant evidence of disease association (P<10-9), several orders of magnitude greater than the observed significance displayed by any other SNP that has previously been associated with disease susceptibility. This observation was replicated in a Gujarati Indian case/control data set. Haplotype-based analysis detected overtransmission of a cluster of chromosomes, which probably originated by ancestral mutation of a common disease-bearing haplotype. The only markers exclusive to the overtransmitted chromosomes are SNPs n.7 and n.9, which define a

  4. The First Genetic and Comparative Map of White Lupin (Lupinus albus L.): Identification of QTLs for Anthracnose Resistance and Flowering Time, and a Locus for Alkaloid Content

    PubMed Central

    Phan, Huyen T. T.; Ellwood, Simon R.; Adhikari, Kedar; Nelson, Matthew N.; Oliver, Richard P.

    2007-01-01

    Abstract We report the first genetic linkage map of white lupin (Lupinus albus L.). An F8 recombinant inbred line population developed from Kiev mutant × P27174 was mapped with 220 amplified fragment length polymorphism and 105 gene-based markers. The genetic map consists of 28 main linkage groups (LGs) that varied in length from 22.7 cM to 246.5 cM and spanned a total length of 2951 cM. There were seven additional pairs and 15 unlinked markers, and 12.8% of markers showed segregation distortion at P < 0.05. Syntenic relationships between Medicago truncatula and L. albus were complex. Forty-five orthologous markers that mapped between M. truncatula and L. albus identified 17 small syntenic blocks, and each M. truncatula chromosome aligned to between one and six syntenic blocks in L. albus. Genetic mapping of three important traits: anthracnose resistance, flowering time, and alkaloid content allowed loci governing these traits to be defined. Two quantitative trait loci (QTLs) with significant effects were identified for anthracnose resistance on LG4 and LG17, and two QTLs were detected for flowering time on the top of LG1 and LG3. Alkaloid content was mapped as a Mendelian trait to LG11. PMID:17526914

  5. Fine Mapping and Candidate Gene Analysis of qSTL3, a Stigma Length-Conditioning Locus in Rice (Oryza sativa L.).

    PubMed

    Liu, Qiangming; Qin, Jiancai; Li, Tianwei; Liu, Erbao; Fan, Dejia; Edzesi, Wisdom Mawuli; Liu, Jianhai; Jiang, Jianhua; Liu, Xiaoli; Xiao, Lianjie; Liu, Linglong; Hong, Delin

    2015-01-01

    The efficiency of hybrid seed production can be improved by increasing the percentage of exserted stigma, which is closely related to the stigma length in rice. In the chromosome segment substitute line (CSSL) population derived from Nipponbare (recipient) and Kasalath (donor), a single CSSL (SSSL14) was found to show a longer stigma length than that of Nipponbare. The difference in stigma length between Nipponbare and SSSL14 was controlled by one locus (qSTL3). Using 7,917 individuals from the SSSL14/Nipponbare F2 population, the qSTL3 locus was delimited to a 19.8-kb region in the middle of the short arm of chromosome 3. Within the 19.8-kb chromosome region, three annotated genes (LOC_Os03g14850, LOC_Os03g14860 and LOC_Os03g14880) were found in the rice genome annotation database. According to gene sequence alignments in LOC_Os03g14850, a transition of G (Nipponbare) to A (Kasalath) was detected at the 474-bp site in CDS. The transition created a stop codon, leading to a deletion of 28 amino acids in the deduced peptide sequence in Kasalath. A T-DNA insertion mutant (05Z11CN28) of LOC_Os03g14850 showed a longer stigma length than that of wild type (Zhonghua 11), validating that LOC_Os03g14850 is the gene controlling stigma length. However, the Kasalath allele of LOC_Os03g14850 is unique because all of the alleles were the same as that of Nipponbare at the 474-bp site in the CDS of LOC_Os03g14850 among the investigated accessions with different stigma lengths. A gene-specific InDel marker LQ30 was developed for improving stigma length during rice hybrid breeding by marker-assisted selection.

  6. Mapping.

    ERIC Educational Resources Information Center

    Kinney, Douglas M.; McIntosh, Willard L.

    1979-01-01

    The area of geological mapping in the United States in 1978 increased greatly over that reported in 1977; state geological maps were added for California, Idaho, Nevada, and Alaska last year. (Author/BB)

  7. Genetic Map Construction and Quantitative Trait Locus (QTL) Detection of Six Economic Traits Using an F2 Population of the Hybrid from Saccharina longissima and Saccharina japonica.

    PubMed

    Zhang, Jing; Liu, Tao; Feng, Rongfang; Liu, Cui; Chi, Shan

    2015-01-01

    Saccharina (Laminaria) is one of the most important economic seaweeds. Previously, four genetic linkage maps of Saccharina have been constructed and five QTLs have been identified. However, they were not enough for its breeding. In this work, Saccharina longissima (♀) and Saccharina japonica (♂), which showed obvious differences in morphology and genetics, were applied in hybridization to yield the F2 mapping population with 102 individuals. Using these 102 F2 hybrids, the genetic linkage map of Saccharina was constructed by MapMaker software based on 37 amplified fragment length polymorphisms (AFLPs), 22 sequence-related amplified polymorphisms (SRAPs) and 139 simple sequence repeats (SSRs) markers. Meanwhile, QTL analysis was performed for six economic traits. The linkage map constructed in this research consisted of 422 marker loci (137 AFLPs, 57 SRAPs and 228 SSRs), which formed 45 linkage groups (LGs) with an average marker space of 7.92 cM; they spanned a total length of 2233.1 cM, covering the whole estimated genome size. A total of 29 QTLs were identified for six economic traits, which explained 1.06 to 64.00% of phenotypic variation, including three QTLs for frond length (FL) and raw weight (RW), five QTLs for frond width (FW), two QTLs for frond fascia width (FFW) and frond thickness (FT), and fourteen QTLs for base shape (BS). The results of this research will improve the breeding efficiency and be beneficial for marker-assisted selection (MAS) schemes in Saccharina breeding.

  8. Genetic Map Construction and Quantitative Trait Locus (QTL) Detection of Six Economic Traits Using an F2 Population of the Hybrid from Saccharina longissima and Saccharina japonica

    PubMed Central

    Zhang, Jing; Liu, Tao; Feng, Rongfang; Liu, Cui; Chi, Shan

    2015-01-01

    Saccharina (Laminaria) is one of the most important economic seaweeds. Previously, four genetic linkage maps of Saccharina have been constructed and five QTLs have been identified. However, they were not enough for its breeding. In this work, Saccharina longissima (♀) and Saccharina japonica (♂), which showed obvious differences in morphology and genetics, were applied in hybridization to yield the F2 mapping population with 102 individuals. Using these 102 F2 hybrids, the genetic linkage map of Saccharina was constructed by MapMaker software based on 37 amplified fragment length polymorphisms (AFLPs), 22 sequence-related amplified polymorphisms (SRAPs) and 139 simple sequence repeats (SSRs) markers. Meanwhile, QTL analysis was performed for six economic traits. The linkage map constructed in this research consisted of 422 marker loci (137 AFLPs, 57 SRAPs and 228 SSRs), which formed 45 linkage groups (LGs) with an average marker space of 7.92 cM; they spanned a total length of 2233.1 cM, covering the whole estimated genome size. A total of 29 QTLs were identified for six economic traits, which explained 1.06 to 64.00% of phenotypic variation, including three QTLs for frond length (FL) and raw weight (RW), five QTLs for frond width (FW), two QTLs for frond fascia width (FFW) and frond thickness (FT), and fourteen QTLs for base shape (BS). The results of this research will improve the breeding efficiency and be beneficial for marker-assisted selection (MAS) schemes in Saccharina breeding. PMID:26010152

  9. High-resolution tyramide-FISH mapping of markers tightly linked to the male-fertility restoration (Ms) locus of onion

    USDA-ARS?s Scientific Manuscript database

    Fluorescence in situ hybridization (FISH) has not been readily exploited for physical mapping of molecular markers in plants due to the technical challenge to visualize small single-copy probes. Signal amplification using tyramide (tyr) FISH can increase sensitivity up to 100 fold. We used tyr-FISH ...

  10. The CAR1 Gene Encoding a Cellular Receptor Specific for Subgroup B and D Avian Leukosis Viruses Maps to the Chicken tvb Locus

    PubMed Central

    Smith, Eugene J.; Brojatsch, Jürgen; Naughton, John; Young, John A. T.

    1998-01-01

    Host susceptibility to subgroup B, D, and E avian leukosis viruses (ALV) is determined by specific alleles of the chicken tvb locus. Recently, a chicken gene that encodes a cellular receptor, designated CAR1, specific for subgroups B and D ALV was cloned, and it was proposed that this gene was the s3 allele of tvb (J. Brojatsch, J. Naughton, M. M. Rolls, K. Zingler, and J. A. T. Young, Cell 87:845–855, 1996). We now report that in a backcross derived from an F1 (Jungle Fowl × White Leghorn [WL]) male mated with inbred WL females, the cloned ALV receptor gene cosegregated with two markers linked to tvb. The two markers used were a tvbs1-specific antigen recognized by the chicken R2 alloantiserum and restriction fragment length polymorphisms associated with the expressed sequence tag com152e. With all three markers, no crossovers were observed among 52 backcross progeny tested and LOD linkage scores of 15.7 were obtained. These data demonstrate that CAR1 is the subgroup B and D ALV susceptibility gene located at tvbs3. PMID:9525691

  11. A gene locus responsible for the familial hair shaft abnormality pili annulati maps to chromosome 12q24.32-24.33.

    PubMed

    Giehl, Kathrin A; Eckstein, Gertrud N; Benet-Pagès, Anna; Tosti, Antonella; de Berker, David A R; Meitinger, Thomas; Müller-Myhsok, Bertram; Strom, Tim M

    2004-12-01

    Pili annulati, a rare hair shaft abnormality with a characteristic shiny appearance due to alternating light and dark bands of the hair, is assumed to be inherited in an autosomal dominant mode with high penetrance. A locus for pili annulati has not been found yet. We identified one large and four small European kindreds with pili annulati and conducted a genomewide linkage analysis using 382 microsatellite markers. A multipoint logarithm of the odds (LOD) score of 3.19 was demonstrated between D12S1659 and D12S1723 on the telomeric part of the long arm of chromosome 12. Subsequent finemapping in a region of 20 cM gave a maximum multipoint LOD score of 3.24 at D12S1723 under the assumption of homogeneity and a LOD score of 3.57 around D12S343 under the assumption of heterogeneity, both exceed the statistical thresholds necessary to conclude linkage. Most of this LOD score came from the largest family, which reached a maximum LOD score of 3.81. The maximum two-point LOD score for all families was 3.97 at D12S1609. Definite recombination events narrowed the region of shared haplotype in the affected individuals to an 8 Mb region between the marker D12S324 and the telomeric end of the long arm of chromosome 12.

  12. High-resolution mapping and characterization of qRgls2, a major quantitative trait locus involved in maize resistance to gray leaf spot.

    PubMed

    Xu, Ling; Zhang, Yan; Shao, Siquan; Chen, Wei; Tan, Jing; Zhu, Mang; Zhong, Tao; Fan, Xingming; Xu, Mingliang

    2014-08-31

    Gray leaf spot (GLS) caused by Cercospora zeae-maydis (Czm) or Cercospora zeina (Cz) is a devastating maize disease and results in substantial yield reductions worldwide. GLS resistance is a quantitatively inherited trait. The development and cultivation of GLS-resistant maize hybrids are the most cost-effective and efficient ways to control this disease. We previously detected a major GLS resistance QTL, qRgls2, in bin 5.03-04, which spans the whole centromere of chromosome 5 encompassing a physical distance of ~110-Mb. With advanced backcross populations derived from the cross between the resistant Y32 and susceptible Q11 inbred lines, a sequential recombinant-derived progeny testing strategy was adapted to fine map qRgls2. We narrowed the region of qRgls2 from an initial ~110-Mb to an interval of ~1-Mb, flanked by the markers G346 and DD11. qRgls2 showed predominantly additive genetic effects and significantly increased the resistance percentage by 20.6 to 24.6% across multiple generations. A total of 15 genes were predicted in the mapped region according to the 5b.60 annotation of the maize B73 genome v2. Two pieces of the mapped qRgls2 region shared collinearity with two distant segments on maize chromosome 4. qRgls2, a major QTL involved in GLS resistance, was mapped to a ~1-Mb region close to the centromere of chromosome 5. There are 15 predicted genes in the mapped region. It is assumed that qRgls2 could be widely used to improve maize resistance to GLS.

  13. Construction of a transcription map of a 300 kb region around the human G6PD locus by direct cDNA selection.

    PubMed

    Sedlacek, Z; Korn, B; Konecki, D S; Siebenhaar, R; Coy, J F; Kioschis, P; Poustka, A

    1993-11-01

    A transcription map covering a 300 kb region around the G6PD gene in the human Xq28 region was constructed by the direct cDNA selection method and the analysis of the resulting region-specific enriched cDNA sublibrary. Seven new genes and two loci of endogenous retrovirus HERV-K were identified. The distribution of the genes across the region is strongly non-uniform and follows the non-uniform distribution of GpG islands in the area. While one of the novel genes was found to be highly homologous to bovine smg p25A GDP-dissociation inhibitor, the remaining genes did not detect any homology to known genes. The analysis of region-specific cDNA sublibraries represents a simple, rapid and efficient tool for the generation of a regional transcription map.

  14. Highly polymorphic locus D15S24 (CMW-1) maps to 15pter-q13. (HGM9 provisional no. D15S24)

    SciTech Connect

    Rich, D.C.; Summers, K.M.; van Tuinen, P.; Ledbetter, D.H. ); Witkowski, C.M. )

    1988-09-12

    CMW-1, containing a 3.8 kb Eco RI fragment, was isolated from a flow sorted library cloned in Charon 21A from the Los Alamos National Laboratory (LA15NS02). The 3.8 kb fragment has also been inserted into the Eco RI site of pUC18. D15S24 maps to chromosome 15, region 15pter-q13, using a somatic cell hybrid regional mapping panel. Co-dominant segregation was shown for alleles detected with Eco RI and Taq I in two informative Caucasian families totaling 17 individuals. Coordinate variation using multiple enzymes suggests that CMW-1 detects a variable number of tandem repeats.

  15. Fine-scale mapping of a locus for severe bipolar mood disorder on chromosome 18p11.3 in the Costa Rican population

    PubMed Central

    McInnes, L. Alison; Service, Susan K.; Reus, Victor I.; Barnes, Glenn; Charlat, Olga; Jawahar, Satya; Lewitzky, Steve; Yang, Qing; Duong, Quyen; Spesny, Mitzi; Araya, Carmen; Araya, Xinia; Gallegos, Alvaro; Meza, Luis; Molina, Julio; Ramirez, Rolando; Mendez, Roxana; Silva, Sandra; Fournier, Eduardo; Batki, Steven L.; Mathews, Carol A.; Neylan, Thomas; Glatt, Charles E.; Escamilla, Michael A.; Luo, David; Gajiwala, Paresh; Song, Terry; Crook, Stephen; Nguyen, Jasmine B.; Roche, Erin; Meyer, Joanne M.; Leon, Pedro; Sandkuijl, Lodewijk A.; Freimer, Nelson B.; Chen, Hong

    2001-01-01

    We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The results of a previous linkage analysis on two extended CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses of a CVCR population sample of BP-I patients implicated a candidate region on 18p11.3. We further investigated this region by creating a physical map and developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for typing in the pedigree and population samples. We report the results of fine-scale association analyses in the population sample, as well as evaluation of haplotypes in pedigree CR001. Our results suggest a candidate region containing six genes but also highlight the complexities of LD mapping of common disorders. PMID:11572994

  16. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval

    SciTech Connect

    Ducros, A.; Alamowitch, S.; Nagy, T.

    1996-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently identified autosomal dominant cerebral arteriopathy characterized by the recurrence of subcortical infarcts leading to dementia. A genetic linkage analysis conducted in two large families recently allowed us to map the affected gene on chromosome 19 in a 12-cM interval bracketed by D19S221 and D19S215. In the present study, these first 2 families and 13 additional ones, including a total of 199 potentially informative meiosis, have been genotyped with eight polymorphic markers located between D19S221 and D19S215. All families were linked to chromosome 19. The highest combined lod score (Z{sub max} = 37.24 at {theta} = .01) was obtained with marker D19S841, a new CA{sub n} microsatellite marker that we isolated from chromosome 19 cosmids. The recombinant events observed within these families were used to refine the genetic mapping of CADASIL within a 2-cM interval that is now bracketed by D19S226 and D19S199 on 19p13.1. These data strongly suggest the genetic homogeneity of this recently identified condition and establish the value of its clinical and neuroimaging diagnostic criteria. Besides their importance for the ongoing positional cloning of the CADASIL gene, these data help to refine the genetic mapping of CADASIL relative to familial hemiplegic migraine and hereditary paroxysmal cerebellar ataxia, conditions that we both mapped within the same chromosome 19 region. 35 refs., 5 figs., 2 tabs.

  17. Genetic map construction and quantitative trait locus (QTL) detection of growth-related traits in Litopenaeus vannamei for selective breeding applications.

    PubMed

    Andriantahina, Farafidy; Liu, Xiaolin; Huang, Hao

    2013-01-01

    Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL) have been regarded as useful for marker-assisted selection (MAS) in complex traits as growth. Using an intermediate F2 cross of slow and fast growth parents, a genetic linkage map of Pacific whiteleg shrimp, Litopenaeusvannamei, based on amplified fragment length polymorphisms (AFLP) and simple sequence repeats (SSR) markers was constructed. Meanwhile, QTL analysis was performed for growth-related traits. The linkage map consisted of 451 marker loci (429 AFLPs and 22 SSRs) which formed 49 linkage groups with an average marker space of 7.6 cM; they spanned a total length of 3627.6 cM, covering 79.50% of estimated genome size. 14 QTLs were identified for growth-related traits, including three QTLs for body weight (BW), total length (TL) and partial carapace length (PCL), two QTLs for body length (BL), one QTL for first abdominal segment depth (FASD), third abdominal segment depth (TASD) and first abdominal segment width (FASW), which explained 2.62 to 61.42% of phenotypic variation. Moreover, comparison of linkage maps between L. vannamei and Penaeusjaponicus was applied, providing a new insight into the genetic base of QTL affecting the growth-related traits. The new results will be useful for conducting MAS breeding schemes in L. vannamei .

  18. Genetic mapping in human and mouse of the locus encoding TRBP, a protein that binds the TAR region of the human immunodeficiency virus (HIV-1)

    SciTech Connect

    Kozak, C.A.; Gatignol, A.; Graham, K.

    1995-01-01

    Productive infection with HIV-1, the virus responsible for AIDS, requires the involvement of host cell factors for completion of the replicative cycle, but the identification of these factors and elucidation of their specific functions has been difficult. A human cDNA, TRBP, was recently cloned and characterized as a positive regulator of gene expression that binds to the TAR region of the HIV-1 genome. Here we demonstrate that this factor is encoded by a gene, TARBP2, that maps to human chromosome 12 and mouse chromosome 15, and we also identify and map one human pseudogene (TARBP2P) and two mouse TRBP-related sequences. The map location of the expressed gene identifies it as a candidate for the previously identified factor encoded on human chromosome 12 that has been shown to be important for expression of HIV-1 genes. Western blotting indicates that despite high sequence conservation in human and mouse, the TARBP2 protein differs in apparent size in primate and rodent cells. 41 refs., 5 figs., 1 tab.

  19. Fine-Mapping of 18q21.1 Locus Identifies Single Nucleotide Polymorphisms Associated with Nonsyndromic Cleft Lip with or without Cleft Palate

    PubMed Central

    Mitra, Amit K.; Stessman, Holly A. F.; Schaefer, Robert J.; Wang, Wen; Myers, Chad L.; Van Ness, Brian G.; Beiraghi, Soraya

    2016-01-01

    Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital birth defects. NSCL/P is a complex multifactorial disease caused by interactions between multiple environmental and genetic factors. However, the causal single nucleotide polymorphism (SNP) signature profile underlying the risk of familial NSCL/P still remains unknown. We previously reported a 5.7-Mb genomic region on chromosome 18q21.1 locus that potentially contributes to autosomal dominant, low-penetrance inheritance of NSCL/P. In the current study, we performed exome sequencing on 12 familial genomes (six affected individuals, two obligate carriers, and four seemingly unaffected individuals) of a six-generation family to identify candidate SNPs associated with NSCL/P risk. Subsequently, targeted bidirectional DNA re-sequencing of polymerase chain reaction (PCR)-amplified high-risk regions of MYO5B gene and sequenom iPLEX genotpying of 29 candidate SNPs were performed on a larger set of 33 members of this NSCL/P family (10 affected + 4 obligate carriers + 19 unaffected relatives) to find SNPs significantly associated with NSCL/P trait. SNP vs. NSCL/P association analysis showed the MYO5B SNP rs183559995 GA genotype had an odds ratio of 18.09 (95% Confidence Interval = 1.86–176.34; gender-adjusted P = 0.0019) compared to the reference GG genotype. Additionally, the following SNPs were also found significantly associated with NSCL/P risk: rs1450425 (LOXHD1), rs6507992 (SKA1), rs78950893 (SMAD7), rs8097060, rs17713847 (SCARNA17), rs6507872 (CTIF), rs8091995 (CTIF), and rs17715416 (MYO5B). We could thus identify mutations in several genes as key candidate SNPs associated with the risk of NSCL/P in this large multi-generation family. PMID:27242896

  20. Evaluation of near-isogenic lines for drought resistance QTL and fine mapping of a locus affecting flag leaf width, spikelet number, and root volume in rice.

    PubMed

    Ding, Xipeng; Li, Xiaokai; Xiong, Lizhong

    2011-09-01

    Drought stress is a major limiting factor for crop production and breeding for drought resistance is very challenging due to the complex nature of this trait. Previous studies in rice suggest that the upland japonica variety IRAT109 shows better drought resistance than the lowland indica variety Zhenshan 97. Numerous quantitative trait loci (QTL) have been previously mapped using a recombinant inbred line population derived from these two genotypes. In this study, near-isogenic lines (NILs) for 17 drought resistance-related QTL were constructed and phenotypic variations of these NILs were investigated under drought and normal conditions. Fourteen of these NILs showed significant phenotypic differences relative to the recurrent parent under at least one of the conditions and nine NILs showed significant differences under both conditions. After eliminating the effect of heading date on drought resistance, only four NILs carrying seven QTL (four for the same grain yield-related traits and three for the same or similar root traits QTL) showed differences consistent with the original QTL mapping results. One of these lines (N19) contains qFSR4, a QTL on chromosome 4 controlling root volume per tiller and co-segregating with flag leaf width and spikelet number per panicle. Using a population derived from N19, qFSR4 was mapped to a 38-kb region containing three open reading frames including the previously characterized NARROW LEAF 1 (NAL1) gene. NAL1, which controls leaf width and also affects vein patterning and polar auxin transport, is the most promising candidate genes for qFSR4. Our results underscore the importance of the development of NILs to confirm the identification of QTL affecting complex traits such as drought resistance.

  1. Nuclear gene for mitochondrial leucyl-tRNA synthetase of Neurospora crassa: isolation, sequence, chromosomal mapping, and evidence that the leu-5 locus specifies structural information.

    PubMed Central

    Chow, C M; Metzenberg, R L; Rajbhandary, U L

    1989-01-01

    We have isolated and characterized the nuclear gene for the mitochondrial leucyl-tRNA synthetase (LeuRS) of Neurospora crassa and have established that a defect in this structural gene is responsible for the leu-5 phenotype. We have purified mitochondrial LeuRS protein, determined its N-terminal sequence, and used this sequence information to identify and isolate a full-length genomic DNA clone. The 3.7-kilobase-pair region representing the structural gene and flanking regions has been sequenced. The 5' ends of the mRNA were mapped by S1 nuclease protection, and the 3' ends were determined from the sequence of cDNA clones. The gene contains a single short intron, 60 base pairs long. The methionine-initiated open reading frame specifies a 52-amino-acid mitochondrial targeting sequence followed by a 942-amino-acid protein. Restriction fragment length polymorphism analyses mapped the mitochondrial LeuRS structural gene to linkage group V, exactly where the leu-5 mutation had been mapped before. We show that the leu-5 strain has a defect in the structural gene for mitochondrial LeuRS by restoring growth under restrictive conditions for this strain after transformation with a wild-type copy of the mitochondrial LeuRS gene. We have cloned the mutant allele present in the leu-5 strain and identified the defect as being due to a Thr-to-Pro change in mitochondrial LeuRS. Finally, we have used immunoblotting to show that despite the apparent lack of mitochondrial LeuRS activity in leu-5 extracts, the leu-5 strain contains levels of mitochondrial LeuRS protein to similar to those of the wild-type strain. Images PMID:2574823

  2. Novel quantitative trait locus is mapped to chromosome 12p11 for left ventricular mass in Dominican families: the Family Study of Stroke Risk and Carotid Atherosclerosis

    PubMed Central

    Wang, Liyong; Beecham, Ashley; Di Tullio, Marco R; Slifer, Susan; Blanton, Susan H; Rundek, Tatjana; Sacco, Ralph L

    2009-01-01

    Background Left ventricular mass (LVM) is an important risk factor for stroke and vascular disease. The genetic basis of LVM is unclear although a high heritability has been suggested. We sought to map quantitative trait loci (QTL) for LVM using large Dominican families. Methods Probands were selected from Dominican subjects of the population-based Northern Manhattan Study (NOMAS). LVM was measured by transthoracic echocardiography. A set of 405 microsatellite markers was used to screen the whole genome among 1360 subjects from 100 Dominican families who had complete phenotype data and DNA available. A polygenic covariate screening was run to identify the significant covariates. Variance components analysis was used to estimate heritability and to detect evidence for linkage, after adjusting for significant risk factors. Ordered-subset Analysis (OSA) was conducted to identify a more homogeneous subset for stratification analysis. Results LVM had a heritability of 0.58 in the studied population (p < 0.0001). The most significant evidence for linkage was found at chromosome 12p11 (MLOD = 3.11, empirical p = 0.0003) with peak marker at D12S1042. This linkage was significantly increased in a subset of families with the high average waist circumference (MLOD = 4.45, p = 0.0045 for increase in evidence for linkage). Conclusion We mapped a novel QTL near D12S1042 for LVM in Dominicans. Enhanced linkage evidence in families with larger waist circumference suggests that gene(s) residing within the QTL interact(s) with abdominal obesity to contribute to phenotypic variation of LVM. Suggestive evidence for linkage (LOD = 1.99) has been reported at the same peak marker for left ventricular geometry in a White population from the HyperGEN study, underscoring the importance of this QTL for left ventricular phenotype. Further fine mapping and validation studies are warranted to identify the underpinning genes. PMID:19627612

  3. High-resolution physical and transcriptional mapping of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3 by FISH.

    PubMed

    Aaltonen, J; Horelli-Kuitunen, N; Fan, J B; Björses, P; Perheentupa, J; Myers, R; Palotie, A; Peltonen, L

    1997-08-01

    Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, PGD type I) is an autosomal recessive disease enriched in the Finnish population. Previously, we have assigned APECED to a 2.6-cM interval on chromosome 21q22.3 by linkage analysis in 14 Finnish families. This subtelomeric region of 21q22.3 seems to have sequence features resulting in its under-representation in large insert genomic libraries, and only a few large insert clones have been available for positional cloning to date. Here, we report the refined localization of the APECED gene and a visual physical map of 800 kb covering the critical chromosomal region for the gene. In the construction of the physical map, the recently developed fiber FISH techniques were essential for the orientation of the cosmid PI, PAC, and BAC clones in relation to each other. We also localized two cDNAs within this genomic region by fiber FISH combined with the highly sensitive tyramide-based detection method. These data will facilitate the final cloning of the APECED gene and any other novel gene in this complex genomic region.

  4. MAPS

    Atmospheric Science Data Center

    2014-07-03

    ... Measurement of Air Pollution from Satellites (MAPS) data were collected during Space Shuttle flights in 1981, ... Facts Correlative Data  - CDIAC - Spring & Fall 1994 - Field and Aircraft Campaigns SCAR-B Block:  ...

  5. Isolation of catalase-deficient Escherichia coli mutants and genetic mapping of katE, a locus that affects catalase activity.

    PubMed Central

    Loewen, P C

    1984-01-01

    A number of catalase-deficient mutants of Escherichia coli which exhibit no assayable catalase activity were isolated. The only physiological difference between the catalase mutants and their parents was a 50- to 60-fold greater sensitivity to killing by hydrogen peroxide. For comparison, mutations in the xthA and recA genes of the same strains increased the sensitivity of the mutants to hydrogen peroxide by seven- and fivefold, respectively, showing that catalase was the primary defense against hydrogen peroxide. One class of mutants named katE was localized between pfkB and xthA at 37.8 min on the E. coli genome. A second class of catalase mutants was found which did not map in this region. PMID:6319370

  6. Identification, Mapping, and Molecular Marker Development for Rgsr8.1: A New Quantitative Trait Locus Conferring Resistance to Gibberella Stalk Rot in Maize (Zea mays L.)

    PubMed Central

    Chen, Qian; Song, Jun; Du, Wen-Ping; Xu, Li-Yuan; Jiang, Yun; Zhang, Jie; Xiang, Xiao-Li; Yu, Gui-Rong

    2017-01-01

    Maize stalk rot is a major fungal disease worldwide, and is difficult to control by chemical methods. Therefore, in maize breeding, quantitative trait loci (QTLs) conferring resistance are important for controlling the disease. Next-generation sequencing technologies are considered a rapid and efficient method to establish the association of agronomic traits with molecular markers or candidate genes. In the present study, we employed QTL-seq, which is a whole-genome resequencing-based approach, to identify candidate genomic regions conferring resistance to maize stalk rot. A novel resistance QTL Rgsr8.1 was finely mapped, conferring broad-spectrum resistance to Gibberella stalk rot (GSR). Segregation analysis in F2 and BC1F1 populations, which were derived from a cross between 18327 (Susceptible) and S72356 (Resistant), indicated that the resistance to GSR was likely to be a quantitatively inherited trait in maize. The result of QTL-seq showed that the resistance to GSR was mapped on chromosome 8 from 161.001 to 170.6 Mb. Based on the simple sequence repeat (SSR) markers, single-nucleotide polymorphism (SNP) markers, and the recombinant test, the location of Rgsr8.1 was narrowed down to 2.04 Mb, flanked by SSR-65 and SNP-25 markers at the physical location from 164.69 to 166.72 Mb based on the maize reference genome. In this region, two candidate resistant genes were found with, one auxin-responsive elements and the other encoding a disease resistance protein. In summary, these results will be useful in maize breeding programs to improve the resistance to GSR in maize. PMID:28824686

  7. Identification, Mapping, and Molecular Marker Development for Rgsr8.1: A New Quantitative Trait Locus Conferring Resistance to Gibberella Stalk Rot in Maize (Zea mays L.).

    PubMed

    Chen, Qian; Song, Jun; Du, Wen-Ping; Xu, Li-Yuan; Jiang, Yun; Zhang, Jie; Xiang, Xiao-Li; Yu, Gui-Rong

    2017-01-01

    Maize stalk rot is a major fungal disease worldwide, and is difficult to control by chemical methods. Therefore, in maize breeding, quantitative trait loci (QTLs) conferring resistance are important for controlling the disease. Next-generation sequencing technologies are considered a rapid and efficient method to establish the association of agronomic traits with molecular markers or candidate genes. In the present study, we employed QTL-seq, which is a whole-genome resequencing-based approach, to identify candidate genomic regions conferring resistance to maize stalk rot. A novel resistance QTL Rgsr8.1 was finely mapped, conferring broad-spectrum resistance to Gibberella stalk rot (GSR). Segregation analysis in F2 and BC1F1 populations, which were derived from a cross between 18327 (Susceptible) and S72356 (Resistant), indicated that the resistance to GSR was likely to be a quantitatively inherited trait in maize. The result of QTL-seq showed that the resistance to GSR was mapped on chromosome 8 from 161.001 to 170.6 Mb. Based on the simple sequence repeat (SSR) markers, single-nucleotide polymorphism (SNP) markers, and the recombinant test, the location of Rgsr8.1 was narrowed down to 2.04 Mb, flanked by SSR-65 and SNP-25 markers at the physical location from 164.69 to 166.72 Mb based on the maize reference genome. In this region, two candidate resistant genes were found with, one auxin-responsive elements and the other encoding a disease resistance protein. In summary, these results will be useful in maize breeding programs to improve the resistance to GSR in maize.

  8. Independence of Foveal Retinal Locus and Visual Detection Paradigm.

    DTIC Science & Technology

    1980-02-09

    F O-AO.. 17 ILLINOIS UNIV AT URBANA-CHAMPAIGN HUMAN ATTENTION RES -ETC F/A 5/10 INDEPENDENCE OF FOVEAL RETINAL LOCUS AND VISUAL DETECTION PARAD -ETC...variably mapped, and frame time of 100 or 200 msec for the consistent or variably mapped conditions, respectively. The main effects of experimental paradigm...Foveal Retinal Locus and Visual Detection Paradigm Walter Schneider and Arthur D. Fisk Report 8001 Human Attention Research Laboratory University of

  9. Hereditary Vascular Retinopathy, Cerebroretinal Vasculopathy, and Hereditary Endotheliopathy with Retinopathy, Nephropathy, and Stroke Map to a Single Locus on Chromosome 3p21.1-p21.3

    PubMed Central

    Ophoff, Roel A.; DeYoung, Joseph; Service, Susan K.; Joosse, Marijke; Caffo, Nathan A.; Sandkuijl, Lodewijk A.; Terwindt, Gisela M.; Haan, Joost; van den Maagdenberg, Arn M. J. M.; Jen, Joanna; Baloh, Robert W.; Barilla-LaBarca, Maria-Louise; Saccone, Nancy L.; Atkinson, John P.; Ferrari, Michel D.; Freimer, Nelson B.; Frants, Rune R.

    2001-01-01

    We performed a genomewide search for linkage in an extended Dutch family with hereditary vascular retinopathy associated with migraine and Raynaud phenomenon. Patients with vascular retinopathy are characterized by microangiopathy of the retina, accompanied by microaneurysms and telangiectatic capillaries. The genome search, using a high throughput capillary sequencer, revealed significant evidence of linkage to chromosome 3p21.1-p21.3 (maximum pairwise LOD score 5.25, with D3S1578). Testing of two additional families that had a similar phenotype, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke, revealed linkage to the same chromosomal region (combined maximum LOD score 6.30, with D3S1588). Haplotype analysis of all three families defined a 3-cM candidate region between D3S1578 and D3S3564. Our study shows that three autosomal dominant vasculopathy syndromes with prominent cerebroretinal manifestations map to the same 3-cM interval on 3p21, suggesting a common locus. PMID:11438888

  10. A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum.

    PubMed

    Blumkin, Lubov; Lerman-Sagie, Tally; Lev, Dorit; Yosovich, Keren; Leshinsky-Silver, Esther

    2011-06-15

    The hereditary spastic paraplegias (HSP) are a heterogeneous group of genetic neurodegenerative disorders in which the main feature is progressive spasticity of the lower limbs due to pyramidal tract dysfunction. Clinically HSP are divided into two forms: a pure form that presents with progressive lower limb spasticity and weakness, sensory signs and bladder dysfunction, and a complicated form, associated with more extensive neurological and extra neurological signs as well as pathological findings on brain imaging. The clinical variability observed in HSP is supported by the large underlying genetic heterogeneity. Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterized by a slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the most frequent gene associated with HSP-TCC, encodes spatacsin, a protein of unknown function. We describe two siblings from an Arabic consanguineous family with slowly progressive spastic paraparesis, mental retardation, seizures, thin corpus callosum and periventricular white matter abnormalities. Homozygosity mapping identified a novel single candidate region of 7.3 Mb on chromosome 1p13.2-1p12. The finding of a new locus for AR-HSP-TCC further demonstrates the extensive genetic heterogeneity of this condition.

  11. 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 Central

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

    2016-01-01

    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

  12. Fine Mapping of Carbon Assimilation Rate 8, a Quantitative Trait Locus for Flag Leaf Nitrogen Content, Stomatal Conductance and Photosynthesis in Rice

    PubMed Central

    Adachi, Shunsuke; Yoshikawa, Kazuaki; Yamanouchi, Utako; Tanabata, Takanari; Sun, Jian; Ookawa, Taiichiro; Yamamoto, Toshio; Sage, Rowan F.; Hirasawa, Tadashi; Yonemaru, Junichi

    2017-01-01

    Increasing the rate of leaf photosynthesis is one important approach for increasing grain yield in rice (Oryza sativa). Exploiting the natural variation in CO2 assimilation rate (A) between rice cultivars using quantitative genetics is one promising means to identify genes contributing to higher photosynthesis. In this study, we determined precise location of Carbon Assimilation Rate 8 (CAR8) by crossing a high-yielding indica cultivar with a Japanese commercial cultivar. Fine mapping suggested that CAR8 encodes a putative Heme Activator Protein 3 (OsHAP3) subunit of a CCAAT-box-binding transcription factor called OsHAP3H. Sequencing analysis revealed that the indica allele of CAR8 has a 1-bp deletion at 322 bp from the start codon, resulting in a truncated protein of 125 amino acids. In addition, CAR8 is identical to DTH8/Ghd8/LHD1, which was reported to control rice flowering date. The increase of A is largely due to an increase of RuBP regeneration rate via increased leaf nitrogen content, and partially explained by reduced stomatal limitation via increased stomatal conductance relative to A. This allele also increases hydraulic conductivity, which would promote higher stomatal conductance. This indicates that CAR8 affects multiple physiological aspects relating to photosynthesis. The detailed analysis of molecular functions of CAR8 would help to understand the association between photosynthesis and flowering and demonstrate specific genetic mechanisms that can be exploited to improve photosynthesis in rice and potentially other crops. PMID:28197156

  13. Genome Editing of the CYP1A1 Locus in iPSCs as a Platform to Map AHR Expression throughout Human Development

    PubMed Central

    Smith, Brenden W.; Stanford, Elizabeth A.; Sherr, David H.; Murphy, George J.

    2016-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that increases the expression of detoxifying enzymes upon ligand stimulation. Recent studies now suggest that novel endogenous roles of the AHR exist throughout development. In an effort to create an optimized model system for the study of AHR signaling in several cellular lineages, we have employed a CRISPR/CAS9 genome editing strategy in induced pluripotent stem cells (iPSCs) to incorporate a reporter cassette at the transcription start site of one of its canonical targets, cytochrome P450 1A1 (CYP1A1). This cell line faithfully reports on CYP1A1 expression, with luciferase levels as its functional readout, when treated with an endogenous AHR ligand (FICZ) at escalating doses. iPSC-derived fibroblast-like cells respond to acute exposure to environmental and endogenous AHR ligands, and iPSC-derived hepatocytes increase CYP1A1 in a similar manner to primary hepatocytes. This cell line is an important innovation that can be used to map AHR activity in discrete cellular subsets throughout developmental ontogeny. As further endogenous ligands are proposed, this line can be used to screen for safety and efficacy and can report on the ability of small molecules to regulate critical cellular processes by modulating the activity of the AHR. PMID:27148368

  14. The human granzyme A (HFSP, CTLA3) gene maps to 5q11-q12 and defines a new locus of the serine protease superfamily

    SciTech Connect

    Fink, T.M.; Lichter, P. ); Wekerle, H.; Zimmer, M.; Jenne, D.E. )

    1993-11-01

    Human granzyme A (HFSP, Hanukah factor serine protease; CTLA3, cytotoxic T-lymphocyte-associated serine esterase-3), a homodimeric, trypsin-like serine protease of 60 kDa found in granules of cytolytic T cells and natural killer cells, is implicated in lymphocyte-mediated target cell lysis. It contributes to DNA fragmentation in perforin (PRF1)-lysed target cells through an unknown mechanism. The authors have isolated a cosmid clone for the functional gene of human granzyme A and established its complete exon-intron map of 10 kb. Using an 11-kb subfragment of the cloned genomic DNA as a probe, they have identified the chromosomal position of human granzyme A on 5q11-q12. Thus, the human granzyme A gene falls into a region of homology between human chromosome 5 and mouse chromosome 13, band D, where the mouse granzyme A gene has been located previously. The granzyme A gene is not linked to known members of the large superfamily of serine proteases. 20 refs., 2 figs.

  15. Fine Mapping of Carbon Assimilation Rate 8, a Quantitative Trait Locus for Flag Leaf Nitrogen Content, Stomatal Conductance and Photosynthesis in Rice.

    PubMed

    Adachi, Shunsuke; Yoshikawa, Kazuaki; Yamanouchi, Utako; Tanabata, Takanari; Sun, Jian; Ookawa, Taiichiro; Yamamoto, Toshio; Sage, Rowan F; Hirasawa, Tadashi; Yonemaru, Junichi

    2017-01-01

    Increasing the rate of leaf photosynthesis is one important approach for increasing grain yield in rice (Oryza sativa). Exploiting the natural variation in CO2 assimilation rate (A) between rice cultivars using quantitative genetics is one promising means to identify genes contributing to higher photosynthesis. In this study, we determined precise location of Carbon Assimilation Rate 8 (CAR8) by crossing a high-yielding indica cultivar with a Japanese commercial cultivar. Fine mapping suggested that CAR8 encodes a putative Heme Activator Protein 3 (OsHAP3) subunit of a CCAAT-box-binding transcription factor called OsHAP3H. Sequencing analysis revealed that the indica allele of CAR8 has a 1-bp deletion at 322 bp from the start codon, resulting in a truncated protein of 125 amino acids. In addition, CAR8 is identical to DTH8/Ghd8/LHD1, which was reported to control rice flowering date. The increase of A is largely due to an increase of RuBP regeneration rate via increased leaf nitrogen content, and partially explained by reduced stomatal limitation via increased stomatal conductance relative to A. This allele also increases hydraulic conductivity, which would promote higher stomatal conductance. This indicates that CAR8 affects multiple physiological aspects relating to photosynthesis. The detailed analysis of molecular functions of CAR8 would help to understand the association between photosynthesis and flowering and demonstrate specific genetic mechanisms that can be exploited to improve photosynthesis in rice and potentially other crops.

  16. Mapping of quantitative trait locus (QTLs) that contribute to germination and early seedling drought tolerance in the interspecific cross Setaria italica×Setaria viridis.

    PubMed

    Qie, Lufeng; Jia, Guanqing; Zhang, Wenying; Schnable, James; Shang, Zhonglin; Li, Wei; Liu, Binhui; Li, Mingzhe; Chai, Yang; Zhi, Hui; Diao, Xianmin

    2014-01-01

    Drought tolerance is an important breeding target for enhancing the yields of grain crop species in arid and semi-arid regions of the world. Two species of Setaria, domesticated foxtail millet (S. italica) and its wild ancestor green foxtail (S. viridis) are becoming widely adopted as models for functional genomics studies in the Panicoid grasses. In this study, the genomic regions controlling germination and early seedling drought tolerance in Setaria were identified using 190 F7 lines derived from a cross between Yugu1, a S. italica cultivar developed in China, and a wild S. viridis genotype collected from Uzbekistan. Quantitative trait loci were identified which contribute to a number of traits including promptness index, radical root length, coleoptile length and lateral root number at germinating stage and seedling survival rate was characterized by the ability of desiccated seedlings to revive after rehydration. A genetic map with 128 SSR markers which spans 1293.9 cM with an average of 14 markers per linkage group of the 9 linkage groups was constructed. A total of eighteen QTLs were detected which included nine that explained over 10% of the phenotypic variance for a given trait. Both the wild green foxtail genotype and the foxtail millet cultivar contributed the favorite alleles for traits detected in this trial, indicating that wild Setaria viridis populations may serve as a reservoir for novel stress tolerance alleles which could be employed in foxtail millet breeding.

  17. Mapping of Quantitative Trait Locus (QTLs) that Contribute to Germination and Early Seedling Drought Tolerance in the Interspecific Cross Setaria italica×Setaria viridis

    PubMed Central

    Qie, Lufeng; Jia, Guanqing; Zhang, Wenying; Schnable, James; Shang, Zhonglin; Li, Wei; Liu, Binhui; Li, Mingzhe; Chai, Yang; Zhi, Hui; Diao, Xianmin

    2014-01-01

    Drought tolerance is an important breeding target for enhancing the yields of grain crop species in arid and semi-arid regions of the world. Two species of Setaria, domesticated foxtail millet (S. italica) and its wild ancestor green foxtail (S. viridis) are becoming widely adopted as models for functional genomics studies in the Panicoid grasses. In this study, the genomic regions controlling germination and early seedling drought tolerance in Setaria were identified using 190 F7 lines derived from a cross between Yugu1, a S. italica cultivar developed in China, and a wild S. viridis genotype collected from Uzbekistan. Quantitative trait loci were identified which contribute to a number of traits including promptness index, radical root length, coleoptile length and lateral root number at germinating stage and seedling survival rate was characterized by the ability of desiccated seedlings to revive after rehydration. A genetic map with 128 SSR markers which spans 1293.9 cM with an average of 14 markers per linkage group of the 9 linkage groups was constructed. A total of eighteen QTLs were detected which included nine that explained over 10% of the phenotypic variance for a given trait. Both the wild green foxtail genotype and the foxtail millet cultivar contributed the favorite alleles for traits detected in this trial, indicating that wild Setaria viridis populations may serve as a reservoir for novel stress tolerance alleles which could be employed in foxtail millet breeding. PMID:25033201

  18. Relationship between Yield Components and Partial Resistance to Lecanicillium fungicola in the Button Mushroom, Agaricus bisporus, Assessed by Quantitative Trait Locus Mapping

    PubMed Central

    Rodier, Anne; Savoie, Jean-Michel

    2012-01-01

    Dry bubble, caused by Lecanicillium fungicola, is one of the most detrimental diseases affecting button mushroom cultivation. In a previous study, we demonstrated that breeding for resistance to this pathogen is quite challenging due to its quantitative inheritance. A second-generation hybrid progeny derived from an intervarietal cross between a wild strain and a commercial cultivar was characterized for L. fungicola resistance under artificial inoculation in three independent experiments. Analysis of quantitative trait loci (QTL) was used to determine the locations, numbers, and effects of genomic regions associated with dry-bubble resistance. Four traits related to resistance were analyzed. Two to four QTL were detected per trait, depending on the experiment. Two genomic regions, on linkage group X (LGX) and LGVIII, were consistently detected in the three experiments. The genomic region on LGX was detected for three of the four variables studied. The total phenotypic variance accounted for by all QTL ranged from 19.3% to 42.1% over all traits in all experiments. For most of the QTL, the favorable allele for resistance came from the wild parent, but for some QTL, the allele that contributed to a higher level of resistance was carried by the cultivar. Comparative mapping with QTL for yield-related traits revealed five colocations between resistance and yield component loci, suggesting that the resistance results from both genetic factors and fitness expression. The consequences for mushroom breeding programs are discussed. PMID:22247161

  19. Relationship between yield components and partial resistance to Lecanicillium fungicola in the button mushroom, Agaricus bisporus, assessed by quantitative trait locus mapping.

    PubMed

    Foulongne-Oriol, Marie; Rodier, Anne; Savoie, Jean-Michel

    2012-04-01

    Dry bubble, caused by Lecanicillium fungicola, is one of the most detrimental diseases affecting button mushroom cultivation. In a previous study, we demonstrated that breeding for resistance to this pathogen is quite challenging due to its quantitative inheritance. A second-generation hybrid progeny derived from an intervarietal cross between a wild strain and a commercial cultivar was characterized for L. fungicola resistance under artificial inoculation in three independent experiments. Analysis of quantitative trait loci (QTL) was used to determine the locations, numbers, and effects of genomic regions associated with dry-bubble resistance. Four traits related to resistance were analyzed. Two to four QTL were detected per trait, depending on the experiment. Two genomic regions, on linkage group X (LGX) and LGVIII, were consistently detected in the three experiments. The genomic region on LGX was detected for three of the four variables studied. The total phenotypic variance accounted for by all QTL ranged from 19.3% to 42.1% over all traits in all experiments. For most of the QTL, the favorable allele for resistance came from the wild parent, but for some QTL, the allele that contributed to a higher level of resistance was carried by the cultivar. Comparative mapping with QTL for yield-related traits revealed five colocations between resistance and yield component loci, suggesting that the resistance results from both genetic factors and fitness expression. The consequences for mushroom breeding programs are discussed.

  20. Molecular analysis of cystinuria in Libyan Jews: Exclusion of the SLC3A1 gene and mapping of a new locus on 19q

    SciTech Connect

    Wartenfeld, R.; Pras, E.; Pras, M.

    1997-03-01

    Cystinuria is a hereditary disorder of amino acid transport and is manifested by the development of kidney stones. In some patients the disease is caused by mutations in the SLC3A1 gene, which is located on the short arm of chromosome 2 and encodes a renal/intestinal transporter for cystine and the dibasic amino acids. In Israel cystinuria is especially common among Jews of Libyan origin. After excluding SLC3A1 as the disease-causing gene in Libyan Jewish patients, we performed a genomewide search that shows that the Libyan Jewish cystinuria gene maps to the long arm of chromosome 19. Significant linkage was obtained for seven chromosome 19 markers. A maximal LOD score of 9.22 was obtained with the marker D19S882. Multipoint data and recombination analysis placed the gene in an 8-cM interval between the markers D19S409 and D19S208. Significant linkage disequilibrium was observed for alleles of four markers, and a specific haplotype comprising the markers D19S225, D19S208, D19S220, and D19S422 was found in 11 of 17 carrier chromosomes, versus 1 of 58 Libyan Jewish noncarrier chromosomes. 40 refs., 2 figs., 3 tabs.

  1. Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case-control study.

    PubMed

    Steele, Natasha Z R; Carr, Jessie S; Bonham, Luke W; Geier, Ethan G; Damotte, Vincent; Miller, Zachary A; Desikan, Rahul S; Boehme, Kevin L; Mukherjee, Shubhabrata; Crane, Paul K; Kauwe, John S K; Kramer, Joel H; Miller, Bruce L; Coppola, Giovanni; Hollenbach, Jill A; Huang, Yadong; Yokoyama, Jennifer S

    2017-03-01

    analyses of class I and II haplotypes further supported the role of class I haplotype A*03:01~B*07:02 (p = 0.03, OR = 1.11 [1.01-1.23]) and class II haplotype DRB1*15:01- DQA1*01:02- DQB1*06:02 (DR15) (p = 0.03, OR = 1.08 [1.01-1.15]) as risk factors for AD. We followed up these findings in the clinical dataset representing the spectrum of cognitively normal controls, individuals with mild cognitive impairment, and individuals with AD to assess their relevance to disease. Carrying A*03:01~B*07:02 was associated with higher CSF amyloid levels (p = 0.03, β ± standard error = 47.19 ± 21.78). We also found a dose-dependent association between the DR15 haplotype and greater rates of cognitive decline (greater impairment on the 11-item Alzheimer's Disease Assessment Scale cognitive subscale [ADAS11] over time [p = 0.03, β ± standard error = 0.7 ± 0.3]; worse forgetting score on the Rey Auditory Verbal Learning Test (RAVLT) over time [p = 0.02, β ± standard error = -0.2 ± 0.06]). In a subset of the same cohort, dose of DR15 was also associated with higher baseline levels of chemokine CC-4, a biomarker of inflammation (p = 0.005, β ± standard error = 0.08 ± 0.03). The main study limitations are that the results represent only individuals of European-ancestry and clinically diagnosed individuals, and that our study used imputed genotypes for a subset of HLA genes. We provide evidence that variation in the HLA locus-including risk haplotype DR15-contributes to AD risk. DR15 has also been associated with multiple sclerosis, and its component alleles have been implicated in Parkinson disease and narcolepsy. Our findings thus raise the possibility that DR15-associated mechanisms may contribute to pan-neuronal disease vulnerability.

  2. Quantitative trait locus mapping based on resampling in a vast maize testcross experiment and its relevance to quantitative genetics for complex traits.

    PubMed

    Schön, Chris C; Utz, H Friedrich; Groh, Susanne; Truberg, Bernd; Openshaw, Steve; Melchinger, Albrecht E

    2004-05-01

    From simulation studies it is known that the allocation of experimental resources has a crucial effect on power of QTL detection as well as on accuracy and precision of QTL estimates. In this study, we used a very large experimental data set composed of 976 F(5) maize testcross progenies evaluated in 19 environments and cross-validation to assess the effect of sample size (N), number of test environments (E), and significance threshold on the number of detected QTL, the proportion of the genotypic variance explained by them, and the corresponding bias of estimates for grain yield, grain moisture, and plant height. In addition, we used computer simulations to compare the usefulness of two cross-validation schemes for obtaining unbiased estimates of QTL effects. The maximum, validated genotypic variance explained by QTL in this study was 52.3% for grain moisture despite the large number of detected QTL, thus confirming the infinitesimal model of quantitative genetics. In both simulated and experimental data, the effect of sample size on power of QTL detection as well as on accuracy and precision of QTL estimates was large. The number of detected QTL and the proportion of genotypic variance explained by QTL generally increased more with increasing N than with increasing E. The average bias of QTL estimates and its range were reduced by increasing N and E. Cross-validation performed well with respect to yielding asymptotically unbiased estimates of the genotypic variance explained by QTL. On the basis of our findings, recommendations for planning of QTL mapping experiments and allocation of experimental resources are given.

  3. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

    PubMed

    Zeng, Chenjie; Guo, Xingyi; Long, Jirong; Kuchenbaecker, Karoline B; Droit, Arnaud; Michailidou, Kyriaki; Ghoussaini, Maya; Kar, Siddhartha; Freeman, Adam; Hopper, John L; Milne, Roger L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Agata, Simona; Ahmed, Shahana; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Arason, Adalgeir; Arndt, Volker; Arun, Banu K; Arver, Brita; Bacot, Francois; Barrowdale, Daniel; Baynes, Caroline; Beeghly-Fadiel, Alicia; Benitez, Javier; Bermisheva, Marina; Blomqvist, Carl; Blot, William J; Bogdanova, Natalia V; Bojesen, Stig E; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Buys, Saundra S; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Carpenter, Jane; Chang-Claude, Jenny; Choi, Ji-Yeob; Claes, Kathleen B M; Clarke, Christine; Cox, Angela; Cross, Simon S; Czene, Kamila; Daly, Mary B; de la Hoya, Miguel; De Leeneer, Kim; Devilee, Peter; Diez, Orland; Domchek, Susan M; Doody, Michele; Dorfling, Cecilia M; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Dwek, Miriam; Dworniczak, Bernd; Egan, Kathleen; Eilber, Ursula; Einbeigi, Zakaria; Ejlertsen, Bent; Ellis, Steve; Frost, Debra; Lalloo, Fiona; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Friedlander, Michael; Friedman, Eitan; Gambino, Gaetana; Gao, Yu-Tang; Garber, Judy; García-Closas, Montserrat; Gehrig, Andrea; Damiola, Francesca; Lesueur, Fabienne; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Giles, Graham G; Godwin, Andrew K; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Hartikainen, Jaana M; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Hogervorst, Frans B L; Verhoef, Senno; Hendricks, Carolyn B; Hillemanns, Peter; Hollestelle, Antoinette; Hulick, Peter J; Hunter, David J; Imyanitov, Evgeny N; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M; Joly Beauparlant, Charles; Jones, Michael; Kabisch, Maria; Kang, Daehee; Karlan, Beth Y; Kauppila, Saila; Kerin, Michael J; Khan, Sofia; Khusnutdinova, Elza; Knight, Julia A; Konstantopoulou, Irene; Kraft, Peter; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Le Marchand, Loic; Lee, Chuen Neng; Lee, Min Hyuk; Lester, Jenny; Li, Jingmei; Liljegren, Annelie; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mai, Phuong L; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; McGuffog, Lesley; Meindl, Alfons; Menegaux, Florence; Montagna, Marco; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Newcomb, Polly A; Nord, Silje; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olswold, Curtis; Osorio, Ana; Papi, Laura; Park-Simon, Tjoung-Won; Paulsson-Karlsson, Ylva; Peeters, Stephanie; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Pfeiler, Georg; Phelan, Catherine M; Presneau, Nadege; Radice, Paolo; Rahman, Nazneen; Ramus, Susan J; Rashid, Muhammad Usman; Rennert, Gad; Rhiem, Kerstin; Rudolph, Anja; Salani, Ritu; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Schoemaker, Minouk J; Schürmann, Peter; Seynaeve, Caroline; Shen, Chen-Yang; Shrubsole, Martha J; Shu, Xiao-Ou; Sigurdson, Alice; Singer, Christian F; Slager, Susan; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Swerdlow, Anthony; Szabo, Csilla I; Tchatchou, Sandrine; Teixeira, Manuel R; Teo, Soo H; Terry, Mary Beth; Tessier, Daniel C; Teulé, Alex; Thomassen, Mads; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda E; Tung, Nadine; Turnbull, Clare; van den Ouweland, Ans M W; van Rensburg, Elizabeth J; Ven den Berg, David; Vijai, Joseph; Wang-Gohrke, Shan; Weitzel, Jeffrey N; Whittemore, Alice S; Winqvist, Robert; Wong, Tien Y; Wu, Anna H; Yannoukakos, Drakoulis; Yu, Jyh-Cherng; Pharoah, Paul D P; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison M; Simard, Jacques; Couch, Fergus J; Antoniou, Antonis C; Easton, Douglas F; Zheng, Wei

    2016-06-21

    Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby

  4. Image simulation using LOCUS

    SciTech Connect

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

    1989-09-01

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

  5. Mapping a barbiturate withdrawal locus to a 0.44 Mb interval and analysis of a novel null mutant identify a role for Kcnj9 (GIRK3) in withdrawal from pentobarbital, zolpidem, and ethanol.

    PubMed

    Kozell, Laura B; Walter, Nicole A R; Milner, Lauren C; Wickman, Kevin; Buck, Kari J

    2009-09-16

    Here, we map a quantitative trait locus (QTL) with a large effect on predisposition to barbiturate (pentobarbital) withdrawal to a 0.44 Mb interval of mouse chromosome 1 syntenic with human 1q23.2. We report a detailed analysis of the genes within this interval and show that it contains 15 known and predicted genes, 12 of which demonstrate validated genotype-dependent transcript expression and/or nonsynonymous coding sequence variation that may underlie the influence of the QTL on withdrawal. These candidates are involved in diverse cellular functions including intracellular trafficking, potassium conductance and spatial buffering, and multimolecular complex dynamics, and indicate both established and novel aspects of neurobiological response to sedative-hypnotics. This work represents a substantial advancement toward identification of the gene(s) that underlie the phenotypic effects of the QTL. We identify Kcnj9 as a particularly promising candidate and report the development of a Kcnj9-null mutant model that exhibits significantly less severe withdrawal from pentobarbital as well as other sedative-hypnotics (zolpidem and ethanol) versus wild-type littermates. Reduced expression of Kcnj9, which encodes GIRK3 (Kir3.3), is associated with less severe sedative-hypnotic withdrawal. A multitude of QTLs for a variety of complex traits, including diverse responses to sedative-hypnotics, have been detected on distal chromosome 1 in mice, and as many as four QTLs on human chromosome 1q have been implicated in human studies of alcohol dependence. Thus, our results will be primary to additional efforts to identify genes involved in a wide variety of behavioral responses to sedative-hypnotics and may directly facilitate progress in human genetics.

  6. Mapping of Mitochondrial Sorting Locus in Cucumber

    USDA-ARS?s Scientific Manuscript database

    In plants, DNA is located in three different places, the chloroplast, mitochondrion, and nucleus. Most angiosperms transmitted their organellar DNA through the egg (mitochondrial DNA), and through the egg and/ or pollen (chloroplast DNA). Transmission of the organellar DNA in cucumber is unique beca...

  7. Identifying regulatory mechanisms underlying tumorigenesis using locus expression signature analysis.

    PubMed

    Lee, Eunjee; de Ridder, Jeroen; Kool, Jaap; Wessels, Lodewyk F A; Bussemaker, Harmen J

    2014-04-15

    Retroviral insertional mutagenesis is a powerful tool for identifying putative cancer genes in mice. To uncover the regulatory mechanisms by which common insertion loci affect downstream processes, we supplemented genotyping data with genome-wide mRNA expression profiling data for 97 tumors induced by retroviral insertional mutagenesis. We developed locus expression signature analysis, an algorithm to construct and interpret the differential gene expression signature associated with each common insertion locus. Comparing locus expression signatures to promoter affinity profiles allowed us to build a detailed map of transcription factors whose protein-level regulatory activity is modulated by a particular locus. We also predicted a large set of drugs that might mitigate the effect of the insertion on tumorigenesis. Taken together, our results demonstrate the potential of a locus-specific signature approach for identifying mammalian regulatory mechanisms in a cancer context.

  8. The IGF2 Locus

    USDA-ARS?s Scientific Manuscript database

    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...

  9. An improved genetic map for Castanea mollissima/Castanea dentata and its relationship to the genetic map of Castanea sativa

    Treesearch

    P.H. Sisco; T.L. Kubisiak; M. Casasoli; T. Barreneche; A. Kremer; C. Clark; R.R. Sederoff; F.V. Hebard; F. Villani

    2005-01-01

    We have added 275 AFLP and 24 SSR markers and the 5SrDNA locus to a previously published genetic map based on a hybrid cross between Castanea mollissima and C. denata. The SSR markers, 5SrDNA locus, and one isozyme locus also permitted us to correlate the linkage groups in the published genetic map of C. sativa...

  10. The R(Pi-mcd1) locus from Solanum microdontum involved in resistance to Phytophthora infestans, causing a delay in infection, maps on potato chromosome 4 in a cluster of NBS-LRR genes.

    PubMed

    Tan, M Y Adillah; Hutten, Ronald C B; Celis, Carolina; Park, Tae-Ho; Niks, Rients E; Visser, Richard G F; van Eck, Herman J

    2008-07-01

    The distinction between field resistance and resistance based on resistance (R) genes has been proven valid for many plant-pathogen interactions. This distinction does not seem to be valid for the interaction between potato and late blight. In this study, a locus involved in late blight resistance, derived from Solanum microdontum, provides additional evidence for this lack of distinction. The resistance is associated with a hypersensitive response and results in a delay of infection of approximately 1 to 2 weeks. Both a quantitative as well as a qualitative genetic approach were used, based on data from a field assay. Quantitative trait locus (QTL) analysis identified a QTL on chromosome 4 after correction of the resistance data for plant maturity. A qualitative genetic analysis resulted in the positioning of this locus on the short arm of chromosome 4 in between amplified fragment length polymorphism marker pCTmACG_310 and cleaved amplified polymorphic sequence markers TG339 and T0703. This position coincides with a conserved Phytophthora R gene cluster which includes R2, R(2-like), R(Pi-blb3), and R(Pi-abpt). This implies that R(Pi-mcd1) is the fifth R gene of this nucleotide-binding site leucine-rich repeat cluster. The implications of our results on R-gene-based and field resistance are discussed.

  11. Construction of a high-density genetic map using specific length amplified fragment markers and identification of a quantitative trait locus for anthracnose resistance in walnut (Juglans regia L.).

    PubMed

    Zhu, Yufeng; Yin, Yanfei; Yang, Keqiang; Li, Jihong; Sang, Yalin; Huang, Long; Fan, Shu

    2015-08-18

    Walnut (Juglans regia, 2n = 32, approximately 606 Mb per 1C genome) is an economically important tree crop. Resistance to anthracnose, caused by Colletotrichum gloeosporioides, is a major objective of walnut genetic improvement in China. The recently developed specific length amplified fragment sequencing (SLAF-seq) is an efficient strategy that can obtain large numbers of markers with sufficient sequence information to construct high-density genetic maps and permits detection of quantitative trait loci (QTLs) for molecular breeding. SLAF-seq generated 161.64 M paired-end reads. 153,820 SLAF markers were obtained, of which 49,174 were polymorphic. 13,635 polymorphic markers were sorted into five segregation types and 2,577 markers of them were used to construct genetic linkage maps: 2,395 of these fell into 16 linkage groups (LGs) for the female map, 448 markers for the male map, and 2,577 markers for the integrated map. Taking into account the size of all LGs, the marker coverage was 2,664.36 cM for the female map, 1,305.58 cM for the male map, and 2,457.82 cM for the integrated map. The average intervals between two adjacent mapped markers were 1.11 cM, 2.91 cM and 0.95 cM for three maps, respectively. 'SNP_only' markers accounted for 89.25% of the markers on the integrated map. Mapping markers contained 5,043 single nucleotide polymorphisms (SNPs) loci, which corresponded to two SNP loci per SLAF marker. According to the integrated map, we used interval mapping (Logarithm of odds, LOD > 3.0) to detect our quantitative trait. One QTL was detected for anthracnose resistance. The interval of this QTL ranged from 165.51 cM to 176.33 cM on LG14, and ten markers in this interval that were above the threshold value were considered to be linked markers to the anthracnose resistance trait. The phenotypic variance explained by each marker ranged from 16.2 to 19.9%, and their LOD scores varied from 3.22 to 4.04. High-density genetic maps for walnut containing 16

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

    PubMed

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

    1991-09-15

    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.

  13. 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).

  14. 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

  15. Fine-Structure Mapping of Meiosis-Specific Double-Strand DNA Breaks at a Recombination Hotspot Associated with an Insertion of Telomeric Sequences Upstream of the His4 Locus in Yeast

    PubMed Central

    Xu, F.; Petes, T. D.

    1996-01-01

    Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand DNA breaks (DSBs). Using two approaches, we mapped the position of DSBs associated with a recombination hotspot created by insertion of telomeric sequences into the region upstream of HIS4. We found that the breaks have no obvious sequence specificity and localize to a region of ~50 bp adjacent to the telomeric insertion. By mapping the breaks and by studies of the exonuclease III sensitivity of the broken ends, we conclude that most of the broken DNA molecules have blunt ends with 3'-hydroxyl groups. PMID:8807286

  16. 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.

  17. Refined mapping and YAC contig construction of the X-linked cleft palate and ankyloglossia locus (CPX) including the proximal X-Y homology breakpoint within Xq21.3

    SciTech Connect

    Forbes, S.A.; Brennan, L.; Richardson, M.

    1996-01-01

    The gene for X-linked cleft palate (CPX) has previously been mapped in an Icelandic kindred between the unordered proximal markers DXS1002/DXS349/DXS95 and the distal marker DXYS1X, which maps to the proximal end of the X-Y homology region in Xq21.3. Using six sequence-tagged sites (STSs) within the region, a total of 91 yeast artificial chromosome (YAC) clones were isolated and overlapped in a single contig that spans approximately 3.1 Mb between DXS1002 and DXYS1X. The order of microsatellite and STS markers in this was established as DXS1002-DXS1168-DXS349-DXS95-DXS364-DXS1196-DXS472-DXS1217-DXYS1X. A long-range restriction map of this region was created using eight nonchimeric, overlapping YAC clones. Analysis of newly positioned polymorphic markers in recombinant individuals from the Icelandic family has enabled us to identify DXS1196 and DXS1217 as the flanking markers for CPX. The maximum physical distance containing the CPX gene has been estimated to be 2.0 Mb, which is spanned by a minimum set of five nonchimeric YAC clones. In addition, YAC end clone and STS analyses have pinpointed the location of the proximal boundary of the X-Y homology region within the map. 40 refs., 2 figs., 2 tabs.

  18. Inside the CBF locus in Poaceae.

    PubMed

    Tondelli, Alessandro; Francia, Enrico; Barabaschi, Delfina; Pasquariello, Marianna; Pecchioni, Nicola

    2011-01-01

    Several molecular evidences have been gathered in Poaceae that point out a central role of the CBF/DREB1 transcription factors in the signal transduction pathways leading to low-temperature tolerance, although to a quite different extent between crops originating from either temperate or tropical climates. A common feature of the CBF/DREB1 genes in Poaceae is their structural organization at the genome level in clusters of tandemly duplicated genes. In temperate cereals such as barley and wheat, expansion of specific multigene phylogenetic clades of CBFs that map at the Frost Resistance-2 locus has been exclusively observed. In addition, copy number variants of CBF genes between frost resistant and frost sensitive genotypes raise the question if multiple copies of the CBF/DREB1s are required to ensure freezing tolerance. On the other hand, in crops of tropical origin such as rice and maize, a smaller or less-responsive CBF regulon may have evolved, and different mechanisms might determine chilling tolerance. In this review, recent advances on the organization and diversity at the CBF cluster locus in the grasses are provided and discussed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  19. Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development—Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus

    PubMed Central

    Dickinson, Peter; Xiong, Anqi; York, Daniel; Jayashankar, Kartika; Pielberg, Gerli; Koltookian, Michele; Murén, Eva; Fuxelius, Hans-Henrik; Weishaupt, Holger; Andersson, Göran; Hedhammar, Åke; Bongcam-Rudloff, Erik; Forsberg-Nilsson, Karin

    2016-01-01

    Gliomas are the most common form of malignant primary brain tumors in humans and second most common in dogs, occurring with similar frequencies in both species. Dogs are valuable spontaneous models of human complex diseases including cancers and may provide insight into disease susceptibility and oncogenesis. Several brachycephalic breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, but others, including Pug and Pekingese, are not at higher risk. To identify glioma-associated genetic susceptibility factors, an across-breed genome-wide association study (GWAS) was performed on 39 dog glioma cases and 141 controls from 25 dog breeds, identifying a genome-wide significant locus on canine chromosome (CFA) 26 (p = 2.8 x 10−8). Targeted re-sequencing of the 3.4 Mb candidate region was performed, followed by genotyping of the 56 SNVs that best fit the association pattern between the re-sequenced cases and controls. We identified three candidate genes that were highly associated with glioma susceptibility: CAMKK2, P2RX7 and DENR. CAMKK2 showed reduced expression in both canine and human brain tumors, and a non-synonymous variant in P2RX7, previously demonstrated to have a 50% decrease in receptor function, was also associated with disease. Thus, one or more of these genes appear to affect glioma susceptibility. PMID:27171399

  20. Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development-Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus.

    PubMed

    Truvé, Katarina; Dickinson, Peter; Xiong, Anqi; York, Daniel; Jayashankar, Kartika; Pielberg, Gerli; Koltookian, Michele; Murén, Eva; Fuxelius, Hans-Henrik; Weishaupt, Holger; Swartling, Fredrik J; Andersson, Göran; Hedhammar, Åke; Bongcam-Rudloff, Erik; Forsberg-Nilsson, Karin; Bannasch, Danika; Lindblad-Toh, Kerstin

    2016-05-01

    Gliomas are the most common form of malignant primary brain tumors in humans and second most common in dogs, occurring with similar frequencies in both species. Dogs are valuable spontaneous models of human complex diseases including cancers and may provide insight into disease susceptibility and oncogenesis. Several brachycephalic breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, but others, including Pug and Pekingese, are not at higher risk. To identify glioma-associated genetic susceptibility factors, an across-breed genome-wide association study (GWAS) was performed on 39 dog glioma cases and 141 controls from 25 dog breeds, identifying a genome-wide significant locus on canine chromosome (CFA) 26 (p = 2.8 x 10-8). Targeted re-sequencing of the 3.4 Mb candidate region was performed, followed by genotyping of the 56 SNVs that best fit the association pattern between the re-sequenced cases and controls. We identified three candidate genes that were highly associated with glioma susceptibility: CAMKK2, P2RX7 and DENR. CAMKK2 showed reduced expression in both canine and human brain tumors, and a non-synonymous variant in P2RX7, previously demonstrated to have a 50% decrease in receptor function, was also associated with disease. Thus, one or more of these genes appear to affect glioma susceptibility.

  1. DNA Modification Study of Major Depressive Disorder: Beyond Locus-by-Locus Comparisons

    PubMed Central

    Oh, Gabriel; Wang, Sun-Chong; Pal, Mrinal; Chen, Zheng Fei; Khare, Tarang; Tochigi, Mamoru; Ng, Catherine; Yang, Yeqing A.; Kwan, Andrew; Kaminsky, Zachary A.; Mill, Jonathan; Gunasinghe, Cerisse; Tackett, Jennifer L.; Gottesman, Irving I.; Willemsen, Gonneke; de Geus, Eco J.C.; Vink, Jacqueline M.; Slagboom, P. Eline; Wray, Naomi R.; Heath, Andrew C.; Montgomery, Grant W.; Turecki, Gustavo; Martin, Nicholas G.; Boomsma, Dorret I.; McGuffin, Peter; Kustra, Rafal; Petronis, Art

    2014-01-01

    Background Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. Methods We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. Results In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. Conclusions Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations. PMID:25108803

  2. 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.

  3. 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).

    PubMed Central

    Fukai, K.; Oh, J.; Karim, M. A.; Moore, K. J.; Kandil, H. H.; Ito, H.; Bürger, J.; Spritz, R. A.

    1996-01-01

    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. PMID:8751863

  4. Cross-species bacterial artificial chromosome (BAC) library screening via overgo-based hybridization and BAC-contig mapping of a yield enhancement quantitative trait locus (QTL) yld1.1 in the Malaysian wild rice Oryza rufipogon.

    PubMed

    Song, Beng-Kah; Nadarajah, Kalaivani; Romanov, Michael N; Ratnam, Wickneswari

    2005-01-01

    The construction of BAC-contig physical maps is an important step towards a partial or ultimate genome sequence analysis. Here, we describe our initial efforts to apply an overgo approach to screen a BAC library of the Malaysian wild rice species, Oryza rufipogon. Overgo design is based on repetitive element masking and sequence uniqueness, and uses short probes (approximately 40 bp), making this method highly efficient and specific. Pairs of 24-bp oligos that contain an 8-bp overlap were developed from the publicly available genomic sequences of the cultivated rice, O. sativa, to generate 20 overgo probes for a 1-Mb region that encompasses a yield enhancement QTL yld1.1 in O. rufipogon. The advantages of a high similarity in melting temperature, hybridization kinetics and specific activities of overgos further enabled a pooling strategy for library screening by filter hybridization. Two pools of ten overgos each were hybridized to high-density filters representing the O. rufipogon genomic BAC library. These screening tests succeeded in providing 69 PCR-verified positive hits from a total of 23,040 BAC clones of the entire O. rufipogon library. A minimal tilling path of clones was generated to contribute to a fully covered BAC-contig map of the targeted 1-Mb region. The developed protocol for overgo design based on O. sativa sequences as a comparative genomic framework, and the pooled overgo hybridization screening technique are suitable means for high-resolution physical mapping and the identification of BAC candidates for sequencing.

  5. [Study on preferred retinal locus].

    PubMed

    Dai, Bing-Fa; Hu, Jian-Min; Xu, Duan-Lian

    2012-03-01

    Preferred retinal locus (PRL) is always found in the age-related macular degeneration and other macular damages in patients with low vision, and it is a very important anatomic position in patients with central vision impairment to achieve the rehabilitation. In recent years, the training of preferred retinal locus (PRL) has become a research hotspot of low vision rehabilitation, it can clearly improve functional vision and quality of life. The authors reviewed relevant literatures, and summarized the definition, position, characteristics, training and clinical implications of the PRL.

  6. Locus of Control and Delinquency.

    ERIC Educational Resources Information Center

    Parrott, C. A.; Strongman, K. T.

    1984-01-01

    Assessed delinquent and nondelinquent male adolescents (N=43) on locus of control and intellectual achievement responsibilty. Results supported a multidimensional model. There was no difference in expectancy of control for negative academic events between delinquents and nondelinquents. Birth order and delinquency were the most important…

  7. Locus of Control and Socialization.

    ERIC Educational Resources Information Center

    Raine, Adrian; And Others

    1982-01-01

    Predicted that an external locus of control would characterize undersocialization. Tested this hypothesis on a random sample of secondary school children (N=97). Scores from the Child Nowicki-Strickland Internal-External Scale were found to predict undersocialization in the expected direction. Suggested several possible interpretations of this…

  8. The gene for autosomal dominant spinocerebellar ataxia (SCAI) maps centromeric to D6S89 and shows no recombination, in nine large kindreds, with a dinucleotide repeat at the AM10 locus

    SciTech Connect

    Kwiatkowski, T.J. Jr.; Zoghbi, H.Y.; Beaudet, A.L.; Banfi, S.; McCall, A.E. ); Orr, H.T.; Duvick, L.A.; Ranum, L.P.W. ); Jodice, C.; Persichetti, F.; Novelletto, A.; Terrenato, L. ); LeBorgne-DeMarquoy, F. ); Subramony, S.H. )

    1993-08-01

    Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder which is genetically linked to the short arm of chromosome 6, telomeric to the human major histocompatibility complex (HLA) and very close to D6S89. Previous multipoint linkage analysis using HLA, D6S89, and SCA1 suggested that SCA1 maps centromeric to D5S89. Data from this study using nine large kindreds indicate a maximum lod score between SCA1 and D6S89 of 67.58 at a maximum recombination fraction of .004. To localize SCA1 more precisely, the authors identified five dinucleotide polymorphisms near D6S89. Genotypic analyses at these polymorphic loci were carried out in nine multigeneration SCA1 kindreds and in the Centre d'Etude du Polymorphisme Humain reference families. A new marker, AM10GA, demonstrates no recombination with SCA1. The maximum lod score for AM10GA linkage to SCA1 is 42.14 at a recombination fraction of 0. Linkage analysis and analysis of recombination events confirm that SCA1 maps centromeric to D6S89 and establish the following order: CEN-D6S109-AM10GA/SCA1-D6S89-LR40-D6S202-TEL. 20 refs., 2 figs., 5 tabs.

  9. Quantitative trait locus mapping in chickens by selective DNA pooling with dinucleotide microsatellite markers by using purified DNA and fresh or frozen red blood cells as applied to marker-assisted selection.

    PubMed

    Lipkin, E; Fulton, J; Cheng, H; Yonash, N; Soller, M

    2002-03-01

    Many large, half-sib sire families are an integral component of chicken genetic improvement programs. These family structures include a sufficient number of individuals for mapping quantitative trait loci (QTL) at high statistical power. However, realizing this statistical power through individual or selective genotyping is yet too costly to be feasible under current genotyping methodologies. Genotyping costs can be greatly reduced through selective DNA pooling, involving densitometric estimates of marker allele frequencies in pooled DNA samples. When using dinucleotide microsatellite markers, however, such estimates are often confounded by overlapping "shadow" bands and can be confounded further by differential amplification of alleles. In the present study a shadow correction procedure provided accurate densitometric estimates of allele frequency for dinucleotide microsatellite markers in pools made from chicken purified DNA samples, fresh blood samples, and frozen-thawed blood samples. In a retrospective study, selective DNA pooling with thawed blood samples successfully identified two QTL previously shown by selective genotyping to affect resistance in chickens to Marek's disease. It is proposed that use of selective DNA pooling can provide relatively low-cost mapping and use in marker-assisted selection of QTL that affect production traits in chickens.

  10. Combined linkage and linkage disequilibrium QTL mapping in multiple families of maize (Zea mays L.) line crosses highlights complementarities between models based on parental haplotype and single locus polymorphism.

    PubMed

    Bardol, N; Ventelon, M; Mangin, B; Jasson, S; Loywick, V; Couton, F; Derue, C; Blanchard, P; Charcosset, A; Moreau, Laurence

    2013-11-01

    Advancements in genotyping are rapidly decreasing marker costs and increasing marker density. This opens new possibilities for mapping quantitative trait loci (QTL), in particular by combining linkage disequilibrium information and linkage analysis (LDLA). In this study, we compared different approaches to detect QTL for four traits of agronomical importance in two large multi-parental datasets of maize (Zea mays L.) of 895 and 928 testcross progenies composed of 7 and 21 biparental families, respectively, and genotyped with 491 markers. We compared to traditional linkage-based methods two LDLA models relying on the dense genotyping of parental lines with 17,728 SNP: one based on a clustering approach of parental line segments into ancestral alleles and one based on single marker information. The two LDLA models generally identified more QTL (60 and 52 QTL in total) than classical linkage models (49 and 44 QTL in total). However, they performed inconsistently over datasets and traits suggesting that a compromise must be found between the reduction of allele number for increasing statistical power and the adequacy of the model to potentially complex allelic variation. For some QTL, the model exclusively based on linkage analysis, which assumed that each parental line carried a different QTL allele, was able to capture remaining variation not explained by LDLA models. These complementarities between models clearly suggest that the different QTL mapping approaches must be considered to capture the different levels of allelic variation at QTL involved in complex traits.

  11. 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)

  12. A Novel 6.14 Mb Duplication of Chromosome 8p21 in a Patient with Autism and Self Mutilation

    ERIC Educational Resources Information Center

    Ozgen, Heval M.; Staal, Wouter G.; Barber, John C.; de Jonge, Maretha V.; Eleveld, Marc J.; Beemer, Frits A.; Hochstenbach, Ron; Poot, Martin

    2009-01-01

    Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with a strong genetic etiology. Cytogenetic abnormalities have been detected in 5-10% of the patients with autism. In this study, we present the clinical, cytogenetic and array-comparative genomic hybridization (array-CGH) evaluation of a 13-year-old male with severe…

  13. A Novel 6.14 Mb Duplication of Chromosome 8p21 in a Patient with Autism and Self Mutilation

    ERIC Educational Resources Information Center

    Ozgen, Heval M.; Staal, Wouter G.; Barber, John C.; de Jonge, Maretha V.; Eleveld, Marc J.; Beemer, Frits A.; Hochstenbach, Ron; Poot, Martin

    2009-01-01

    Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with a strong genetic etiology. Cytogenetic abnormalities have been detected in 5-10% of the patients with autism. In this study, we present the clinical, cytogenetic and array-comparative genomic hybridization (array-CGH) evaluation of a 13-year-old male with severe…

  14. Identification of QTLs for serum lipid levels in a female sib-pair cohort: a novel application to improve the power of two-locus linkage analysis.

    PubMed

    Falchi, Mario; Andrew, Toby; Snieder, Harold; Swaminathan, Ramasamyiyer; Surdulescu, Gabriela L; Spector, Tim D

    2005-10-15

    Using a novel approach for a two-locus model that provides a greatly increased power to detect multiple quantitative trait loci (QTLs) in simulated data, we identified in a sample of 961 female sib-pairs, three genome-wide significant QTLs for apolipoprotein A1 on chromosomes 8p21.1-q13.1 (LOD score 3.71), 9q21.32-33.1 (LOD score 3.28) and 10p15.1-p13 (LOD score 5.51), two for lipoprotein (a) on chromosomes 6q25.2-q27 (LOD score 10.18) and 21q21.1-q21.3 (LOD score 4.57) and two for triglycerides on chromosomes 4q28.3-32.1 (LOD score 3.71) and 5q23.1-q32 (LOD score 3.60). The two-locus ordered-subset analysis has led to the confirmation of known and likely identification of novel regions linked to serum lipid levels that would have otherwise been missed and deserves wider application in linkage analyses of quantitative traits. Given the relative lack of power for the sample sizes commonly used in human genetics linkage studies, minor QTL effects often go undetected and those that are detected will be upwardly biased. We show through simulation that the discrepancy between the real and estimated QTL-effects is often likely to generate an unpredictable source of false-negative errors, using multi-locus models, reducing the power to detect multiple QTLs through oligogenic linkage analysis. The successful simultaneous modelling of the identified QTLs in a multi-locus context helps to eliminate false positives and increases the power to detect linkages, adding compelling evidence that they are likely to be reliable QTLs for these lipid traits.

  15. 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…

  16. Which Sry locus is the hypertensive Y chromosome locus?

    PubMed

    Turner, Monte E; Farkas, Joel; Dunmire, Jeff; Ely, Daniel; Milsted, Amy

    2009-02-01

    The Y chromosome of the spontaneously hypertensive rat (SHR) contains a genetic component that raises blood pressure compared with the Wistar-Kyoto (WKY) Y chromosome. This research tests the Sry gene complex as the hypertensive component of the SHR Y chromosome. The Sry loci were sequenced in 1 strain with a hypertensive Y chromosome (SHR/Akr) and 2 strains with a normotensive Y chromosome (SHR/Crl and WKY/Akr). Both SHR strains have 7 Sry loci, whereas the WKY strain has 6. The 6 loci in common between SHR and WKY strains were identical in the sequence compared (coding region, 392-bp 5' prime flanking, 1200-bp 3' flanking). Both SHR strains have a locus (Sry3) not found in WKY rats, but this locus is different between SHR/Akr and SHR/Crl rats. Six mutations have accumulated in Sry3 between the SHR strains, whereas the other 6 Sry loci are identical. This pattern of an SHR-specific locus and mutation in this locus in SHR/Crl coinciding with the loss of Y chromosome hypertension is an expected pattern if Sry3 is the Y chromosome-hypertensive component. The SHR/y strain showed a significant increase in total Sry expression in the kidney between 4 and 15 weeks of age. There are significant differences in Sry expression between adrenal glands and the kidney (15 to 30 times higher in kidneys) but no significant differences between strains. These results, along with previous studies demonstrating an interaction of Sry with the tyrosine hydroxylase promoter and increased blood pressure with exogenous Sry expression, suggest the Sry loci as the hypertensive component of the SHR Y chromosome.

  17. 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.

  18. Speaking rate effects on locus equation slope

    PubMed Central

    Berry, Jeff; Weismer, Gary

    2013-01-01

    A locus equation describes a 1st order regression fit to a scatter of vowel steady-state frequency values predicting vowel onset frequency values. Locus equation coefficients are often interpreted as indices of coarticulation. Speaking rate variations with a constant consonant–vowel form are thought to induce changes in the degree of coarticulation. In the current work, the hypothesis that locus slope is a transparent index of coarticulation is examined through the analysis of acoustic samples of large-scale, nearly continuous variations in speaking rate. Following the methodological conventions for locus equation derivation, data pooled across ten vowels yield locus equation slopes that are mostly consistent with the hypothesis that locus equations vary systematically with coarticulation. Comparable analyses between different four-vowel pools reveal variations in the locus slope range and changes in locus slope sensitivity to rate change. Analyses across rate but within vowels are substantially less consistent with the locus hypothesis. Taken together, these findings suggest that the practice of vowel pooling exerts a non-negligible influence on locus outcomes. Results are discussed within the context of articulatory accounts of locus equations and the effects of speaking rate change. PMID:24535890

  19. Speaking rate effects on locus equation slope.

    PubMed

    Berry, Jeff; Weismer, Gary

    2013-11-01

    A locus equation describes a 1st order regression fit to a scatter of vowel steady-state frequency values predicting vowel onset frequency values. Locus equation coefficients are often interpreted as indices of coarticulation. Speaking rate variations with a constant consonant-vowel form are thought to induce changes in the degree of coarticulation. In the current work, the hypothesis that locus slope is a transparent index of coarticulation is examined through the analysis of acoustic samples of large-scale, nearly continuous variations in speaking rate. Following the methodological conventions for locus equation derivation, data pooled across ten vowels yield locus equation slopes that are mostly consistent with the hypothesis that locus equations vary systematically with coarticulation. Comparable analyses between different four-vowel pools reveal variations in the locus slope range and changes in locus slope sensitivity to rate change. Analyses across rate but within vowels are substantially less consistent with the locus hypothesis. Taken together, these findings suggest that the practice of vowel pooling exerts a non-negligible influence on locus outcomes. Results are discussed within the context of articulatory accounts of locus equations and the effects of speaking rate change.

  20. A locus affecting nucleoid segregation in Salmonella typhimurium.

    PubMed Central

    Schmid, M B

    1990-01-01

    Thirteen temperature-sensitive lethal mutations of Salmonella typhimurium map near metC at 65 min and form the clmF (conditional lethal mutation) locus. The mutations in this region were ordered by three-point transduction crosses. After a shift to the nonpermissive temperature, many of these clmF mutants failed to complete the segregation of nucleoids into daughter cells; daughter nucleoids appeared incompletely separated and asymmetrically positioned within cells. Some clmF mutants showed instability of F' episomes at permissive growth temperatures yet showed no detectable defect with smaller multicopy plasmids such as pSC101 or pBR322. In addition, many of the clmF mutants rapidly lost viability yet continued DNA replication at the nonpermissive temperature. These results suggest that the clmF locus encodes at least one indispensable gene product that is required for faithful partitioning of the bacterial nucleoid and F-plasmid replicons. Images PMID:2203751