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Sample records for 8p21 mapped locus

  1. Submicroscopic deletions of 3p sequences in pleomorphic adenomas with t(3;8)(p21;q12).

    PubMed

    Sahlin, P; Mark, J; Stenman, G

    1994-08-01

    A subgroup of benign pleomorphic adenomas of the salivary glands is characterized by translocations, or on rare occasions deletions, with breakpoints at 3p21. We have applied restriction fragment length polymorphism (RFLP) analysis to assess the frequency of allelic losses at four different loci located within 3p21-->p25 in 35 pleomorphic adenomas, 18 of which were also karyotyped. Parallel analysis of constitutional and tumor DNAs in informative tumors revealed that all patients retained heterozygosity in their tumor DNA at the D3S2 and RAF1 loci. Among the 29 tumors informative for THRB three showed loss of heterozygosity (LOH). All three tumors had a t(3;8)(p21;q12). Of the 23 tumors informative for D3F15S2, one showed LOH. This tumor also had a t(3;8)(p21;q12). To further map the deletions in relation to the 3p21 translocation breakpoint, we also sublocalized the THRB locus. Using in situ hybridization we assigned the gene to 3p24.1-3. The fact that none of the tumors with loss of 3p alleles showed cytogenetic evidence of deletions indicates that the losses are submicroscopic, probably interstitial, and in most cases distal to the 3p21 breakpoint. This was confirmed in one case with loss of a THRB allele where both proximal (D3F15S2) and distal (RAF1) markers retained heterozygosity. Our results suggest that deletion of 3p sequences might be of progressional importance in a subset of pleomorphic adenomas with t(3;8)(p21;q12).

  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. Molecular Mapping of the ROSY Locus in DROSOPHILA MELANOGASTER

    PubMed Central

    Coté, Babette; Bender, Welcome; Curtis, Daniel; Chovnick, Arthur

    1986-01-01

    The DNA from the chromosomal region of the Drosophila rosy locus has been examined in 83 rosy mutant strains. Several spontaneous and radiation-induced alleles were associated with insertions and deletions, respectively. The lesions are clustered in a 4-kb region. Some of the alleles identified on the DNA map have been located on the genetic map by fine-structure recombination experiments. The genetic and molecular maps are collinear, and the alignment identifies the DNA location of the rosy control region. A rosy RNA of 4.5 kb has been identified; its 5' end lies in or near the control region. PMID:2420682

  5. 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.

  6. On loops in the hyperbolic locus of the complex Hénon map and their monodromies

    NASA Astrophysics Data System (ADS)

    Arai, Zin

    2016-11-01

    We prove John Hubbard's conjecture on the topological complexity of the hyperbolic horseshoe locus of the complex Hénon map. In fact, we show that there exist several non-trivial loops in the locus which generate infinitely many mutually different monodromies. Furthermore, we prove that the dynamics of the real Hénon map is completely determined by the monodromy of the complex Hénon map, providing the parameter of the map is contained in the hyperbolic horseshoe locus.

  7. Mapping of crown gall resistance locus Rcg1 in grapevine.

    PubMed

    Kuczmog, Anett; Galambos, Anikó; Horváth, Szabina; Mátai, Anikó; Kozma, Pál; Szegedi, Ernő; Putnoky, Péter

    2012-11-01

    Agrobacteria are efficient plant pathogens. They are able to transform plant cells genetically resulting in abnormal cell proliferation. Cultivars of Vitis vinifera are highly susceptible to many virulent Agrobacterium strains but certain wild Vitis species, including Vitis amurensis have resistant genotypes. Studies of the molecular background of such natural resistance are of special importance, not only for practical benefits in agricultural practice but also for understanding the role of plant genes in the transformation process. Earlier, crown gall resistance from V. amurensis was introgressed into V. vinifera through interspecific breeding and it was shown to be inherited as a single and dominant Mendelian trait. To develop this research further, towards understanding underlying molecular mechanisms, a mapping population was established, and resistance-coupled molecular DNA markers were identified by three different approaches. First, RAPD makers linked to the resistance locus (Rcg1) were identified, and on the basis of their DNA sequences, we developed resistance-coupled SCAR markers. However, localization of these markers in the grapevine genome sequence failed due to their similarity to many repetitive regions. Next, using SSR markers of the grapevine reference linkage map, location of the resistance locus was established on linkage group 15 (LG15). Finally, this position was supported further by developing new chromosome-specific markers and by the construction of the genetic map of the region including nine loci in 29.1 cM. Our results show that the closest marker is located 3.3 cM from the Rcg1 locus that may correspond to 576 kb. PMID:22801874

  8. Mapping of crown gall resistance locus Rcg1 in grapevine.

    PubMed

    Kuczmog, Anett; Galambos, Anikó; Horváth, Szabina; Mátai, Anikó; Kozma, Pál; Szegedi, Ernő; Putnoky, Péter

    2012-11-01

    Agrobacteria are efficient plant pathogens. They are able to transform plant cells genetically resulting in abnormal cell proliferation. Cultivars of Vitis vinifera are highly susceptible to many virulent Agrobacterium strains but certain wild Vitis species, including Vitis amurensis have resistant genotypes. Studies of the molecular background of such natural resistance are of special importance, not only for practical benefits in agricultural practice but also for understanding the role of plant genes in the transformation process. Earlier, crown gall resistance from V. amurensis was introgressed into V. vinifera through interspecific breeding and it was shown to be inherited as a single and dominant Mendelian trait. To develop this research further, towards understanding underlying molecular mechanisms, a mapping population was established, and resistance-coupled molecular DNA markers were identified by three different approaches. First, RAPD makers linked to the resistance locus (Rcg1) were identified, and on the basis of their DNA sequences, we developed resistance-coupled SCAR markers. However, localization of these markers in the grapevine genome sequence failed due to their similarity to many repetitive regions. Next, using SSR markers of the grapevine reference linkage map, location of the resistance locus was established on linkage group 15 (LG15). Finally, this position was supported further by developing new chromosome-specific markers and by the construction of the genetic map of the region including nine loci in 29.1 cM. Our results show that the closest marker is located 3.3 cM from the Rcg1 locus that may correspond to 576 kb.

  9. Deletion of Chromosomal Region 8p21 Confers Resistance to Bortezomib and Is Associated with Upregulated Decoy TRAIL Receptor Expression in Patients with Multiple Myeloma.

    PubMed

    Duru, Adil Doganay; Sutlu, Tolga; Wallblom, Ann; Uttervall, Katarina; Lund, Johan; Stellan, Birgitta; Gahrton, Gösta; Nahi, Hareth; Alici, Evren

    2015-01-01

    Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM) that undergo autologous stem cell transplantation (ASCT). In this study, we aimed to identify the immunological and molecular consequences of del(8)(p21) with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8)(p21) responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8)(p21) to TRAIL/APO2L mediated apoptosis, in cells with del(8)(p21) bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8)(p21) to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8)(p21). PMID:26378933

  10. Deletion of Chromosomal Region 8p21 Confers Resistance to Bortezomib and Is Associated with Upregulated Decoy TRAIL Receptor Expression in Patients with Multiple Myeloma.

    PubMed

    Duru, Adil Doganay; Sutlu, Tolga; Wallblom, Ann; Uttervall, Katarina; Lund, Johan; Stellan, Birgitta; Gahrton, Gösta; Nahi, Hareth; Alici, Evren

    2015-01-01

    Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM) that undergo autologous stem cell transplantation (ASCT). In this study, we aimed to identify the immunological and molecular consequences of del(8)(p21) with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8)(p21) responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8)(p21) to TRAIL/APO2L mediated apoptosis, in cells with del(8)(p21) bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8)(p21) to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8)(p21).

  11. 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.

  12. 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

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

    SciTech Connect

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

    1994-09-01

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

  14. Localization of the gene for hyperostosis cranialis interna to chromosome 8p21 with analysis of three candidate genes.

    PubMed

    Borra, V M; Waterval, J J; Stokroos, R J; Manni, J J; Van Hul, W

    2013-07-01

    Hyperostosis cranialis interna (HCI) is a rare autosomal dominant disorder characterized by intracranial hyperostosis and osteosclerosis, which is confined to the skull, especially the calvarium and the skull base. The rest of the skeleton is not affected. Progressive bone overgrowth causes nerve entrapment that leads to recurrent facial nerve palsy, disturbance of the sense of smell, hearing and vision impairments, impairment of facial sensibility, and disturbance of balance due to vestibular areflexia. The treatment is symptomatic. Histomorphological investigations showed increased bone formation with a normal tissue structure. Biochemical parameters were normal. Until today the disease has been described in only three related Dutch families with common progenitors and which consist of 32 individuals over five generations. HCI was observed in 12 family members over four generations. Patients are mildly to severely affected. Besides HCI, several bone dysplasias with hyperostosis and sclerosis of the craniofacial bones are known. Examples are Van Buchem disease, sclerosteosis, craniometaphyseal dysplasia, and Camurati-Engelmann disease. However, in these cases the long bones are affected as well. Linkage analysis in a family with HCI resulted in the localization of the disease-causing gene to a region on chromosome 8p21 delineated by markers D8S282 and D8S382. Interesting candidate genes in this region are BMP1, LOXL2, and ADAM28. Sequence analysis of these genes did not reveal any putative mutations. This suggests that a gene not previously involved in a sclerosing bone dysplasia is responsible for the abnormal growth in the skull of these patients.

  15. Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes.

    PubMed

    Rubio-Moscardo, Fanny; Blesa, David; Mestre, Cinta; Siebert, Reiner; Balasas, Theo; Benito, Adalberto; Rosenwald, Andreas; Climent, Joan; Martinez, Jose I; Schilhabel, Markus; Karran, E Lorraine; Gesk, Stefan; Esteller, Manel; deLeeuw, Ronald; Staudt, Louis M; Fernandez-Luna, Jose Luis; Pinkel, Daniel; Dyer, Martin J S; Martinez-Climent, Jose A

    2005-11-01

    Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma. PMID:16051735

  16. Heterotic Trait Locus (HTL) Mapping Identifies Intra-Locus Interactions That Underlie Reproductive Hybrid Vigor in Sorghum bicolor

    PubMed Central

    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. PMID:22761720

  17. 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.

  18. 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.

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

    PubMed Central

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

    1996-01-01

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

  20. Physical Mapping in a Triplicated Genome: Mapping the Downy Mildew Resistance Locus Pp523 in Brassica oleracea L.

    PubMed Central

    Carlier, Jorge D.; Alabaça, Claudia S.; Sousa, Nelson H.; Coelho, Paula S.; Monteiro, António A.; Paterson, Andrew H.; Leitão, José M.

    2011-01-01

    We describe the construction of a BAC contig and identification of a minimal tiling path that encompass the dominant and monogenically inherited downy mildew resistance locus Pp523 of Brassica oleracea L. The selection of BAC clones for construction of the physical map was carried out by screening gridded BAC libraries with DNA overgo probes derived from both genetically mapped DNA markers flanking the locus of interest and BAC-end sequences that align to Arabidopsis thaliana sequences within the previously identified syntenic region. The selected BAC clones consistently mapped to three different genomic regions of B. oleracea. Although 83 BAC clones were accurately mapped within a ∼4.6 cM region surrounding the downy mildew resistance locus Pp523, a subset of 33 BAC clones mapped to another region on chromosome C8 that was ∼60 cM away from the resistance gene, and a subset of 63 BAC clones mapped to chromosome C5. These results reflect the triplication of the Brassica genomes since their divergence from a common ancestor shared with A. thaliana, and they are consonant with recent analyses of the C genome of Brassica napus. The assembly of a minimal tiling path constituted by 13 (BoT01) BAC clones that span the Pp523 locus sets the stage for map-based cloning of this resistance gene. PMID:22384370

  1. 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.

  2. 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.

  3. Genetic mapping of a locus predisposing to human colorectal cancer

    SciTech Connect

    Peltomaeki, P.; Aaltonen, L.A.; Pylkkaenen, L.; Chappelle, A. de la ); Sistonen, P. Finnish Red Cross Blood Transfusion Service, Helsinki ); Mecklin, J.P. ); Haervinen, H. ); Green, J.S. ); Jass, J.R. ); Weber, J.L. ); Leach, F.S.; Petersen, G.M.; Hamilton, S.R.; Vogelstein, B. Johns Hopkins Hospital, Baltimore, MD )

    1993-05-07

    Genetic linkage analysis was used to determine whether a specific chromosomal locus could be implicated in families with a history of early onset cancer but with no other unique features. Close linkage of disease to anonymous microsatellite markers on chromosome 2 was demonstrated in two large kindreds. The pairwise lod scores for linkage to marker D2S123 in these kindreds were 6.39 and 1.45 at zero recombination, and multipoint linkage with flanking markers resulted in lod scores of 6.47 and 6.01. These results prove the existence of a genetically determined predisposition to colorectal cancer that has important ramifications for understanding and preventing this disease. 13 refs., 1 fig., 1 tab.

  4. 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. PMID:10330355

  5. 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

  6. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. A New Map Location for the ilvB Locus of ESCHERICHIA COLI

    PubMed Central

    Newman, Thomas C.; Levinthal, Mark

    1980-01-01

    We isolated, in E. coli K12, new alleles of the ilvB locus, the structural gene for acetolactate synthase isoenzyme I, and showed them to map at or near the ilvB619 site. The map position of the ilvB locus was redetermined because plasmids containing the ilvC-cya portion of the chromosome did not complement mutations at the ilvB locus. Furthermore, diploids for the ilvEDAC genes formed with these plasmids in an ilvHI background facilitated the isolation of the new ilvB alleles. The ilvB locus was remapped and found to be located at 81.5 minutes, between the uhp and dnaA loci. This location was determined by two- and three-point transductional crosses, deletion mapping and complementation with newly isolated plasmids. One of the new alleles of the ilvB gene is a mu-1 insertion. When present in the donor strain, this allele interferes with the linkage of genes flanking the mu-1 insertion, as well as the linkage of genes to either side of the mu-1 insertion. PMID:7009323

  9. 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

  10. [Mapping a new secalin locus on the rye iRS arm].

    PubMed

    Kozub, N O; Motsnyĭ, I I; Sozinov, I O; Blium, Ia B; Sizinov, O O

    2014-01-01

    A gene designated Sec-N encoding secalin was mapped in the introgressive winter common wheat line Hostianum 273/97 (H273) with the wheat-rye substitution (1B)1R from the octoploid triticale AD825. F2 seeds from crossing the line H273 with the line Hostianum 242/97-2 carrying the wheat-rye 1BL/1RS translocation were analysed. The studied component on the SDS-electrophoregram of total proteins was revealed to be a monomeric secalin which is encoded by the gene at the new locus Sec-N located distally with respect to the Sec-1 locus at a distance of 21.4 +/- 2.5% (22.9 +/- 3.1 cM). The arrangement of the secalin loci on the 1RS arm indicates that the Sec-N locus is to be homoeologous to the Gli-1 loci of common wheat. PMID:25184199

  11. 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.

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

    SciTech Connect

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

    1996-02-01

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

  13. 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.

  14. 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.

  15. Interval Mapping of High Growth (Hg), a Major Locus That Increases Weight Gain in Mice

    PubMed Central

    Horvat, S.; Medrano, J. F.

    1995-01-01

    The high growth locus (hg) causes a major increase in weight gain and body size in mice. As a first step to map-based cloning of hg, we developed a genetic map of the hg-containing region using interval mapping of 403 F(2) from a C57BL/6J-hghg X CAST/EiJ cross. The maximum likelihood position of hg was at the chromosome 10 marker D10Mit41 (LOD = 24.8) in the F(2) females and 1.5 cM distal to D10Mit41 (LOD = 9.56) in the F(2) males with corresponding LOD 2 support intervals of 3.7 and 5.4 cM, respectively. The peak LOD scores were significantly higher than the estimated empirical threshold LOD values. The localization of hg by interval mapping was supported by a test cross of F(2) mice recombinant between the LOD 2 support interval and the flanking marker. The interval mapping and test-cross results indicate that hg is not allelic with candidate genes Igf1 or decorin (Dcn), a gene that was mapped close to hg in this study. The hg inheritance was recessive in females, although we could not reject recessive or additive inheritance in males. Possible causes for sex differences in peak LOD scores and for the distortion of transmission ratios observed in F(2) males are discussed. The genetic map of the hg region will facilitate further fine mapping and cloning of hg, and allow searches for a homologous quantitative trait locus affecting growth in humans and domestic animals. PMID:7789774

  16. 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.

  17. Mapping of the Hor-3 locus encoding D hordein in Barley.

    PubMed

    Blake, T K; Ullrich, S E; Nilan, R A

    1982-12-01

    The hordein storage proteins of barley (Hordeum vulgare L.) are of intense interest due to their genetic diversity and prominence and impact on the industrial and agricultural uses of the seed. Two major hordein loci have been previously mapped on chromosome 5 (Hor-1 and Hor-2 encoding the C and B hordeins, respectively). A third major locus, Hor-3, which codes for D hordein, has been located in the centromeric region of chromosome 5, probably on the long arm. Two allelic variants with apparent molecular weights of 83,000 and 91,000 and similar isoelectric points of 8.0 comprise the products of this locus in the barley varieties 'Advance' and 'Triple Awned Lemma'. The D hordein examined is similar in molecular weight and isoelectric point to the high molecular weight (HMW) glutenin proteins encoded by the 1B chromosome of wheat (Triticum aestivum L.).

  18. 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.

  19. The Finnish lapphund retinal atrophy locus maps to the centromeric region of CFA9

    PubMed Central

    Aguirre-Hernández, Jesús; Wickström, Kaisa; Sargan, David R

    2007-01-01

    Background Dogs have the second largest number of genetic diseases, after humans. Among the diseases present in dogs, progressive retinal atrophy has been reported in more than a hundred breeds. In some of them, the mutation has been identified and genetic tests have allowed the identification of carriers, thus enabling a drastic reduction in the incidence of the disease. The Finnish lapphund is a dog breed presenting late-onset progressive retinal atrophy for which the disease locus remains unknown. Results In this study we mapped the progressive retinal atrophy locus in the Finnish lapphund using a DNA pooling approach, assuming that all affected dogs within the breed share the same identical-by descent-mutation as the cause of the disease (genetic homogeneity). Autosomal recessive inheritance was also assumed, after ruling out, from pedigree analysis, dominant and X-linked inheritance. DNA from 12 Finnish lapphund cases was mixed in one pool, and DNA from 12 first-degree relatives of these cases was mixed to serve as the control pool. The 2 pools were tested with 133 microsatellite markers, 3 of which showed a shift towards homozygosity in the cases. Individual genotyping with these 3 markers confirmed homozygosity for the GALK1 microsatellite only (chromosome 9). Further individual genotyping with additional samples (4 cases and 59 controls) confirmed the association between this marker and the disease locus (p < 0.001). Closely related to this breed are the Swedish lapphund and the Lapponian herder for which a small number of retinal atrophy cases have been reported. Swedish lapphund cases, but not Lapponian herder cases, had the same GALK1 microsatellite genotype as Finnish lapphund cases. Conclusion The locus for progressive rod-cone degeneration is known to be close to the GALK1 locus, on the telomeric region of chromosome 9, where the retinal atrophy locus of the Finnish lapphund has been mapped. This suggests that the disease in this breed, as well as in

  20. Quantitative Trait Locus Mapping Reveals Regions of the Maize Genome Controlling Root System Architecture1[OPEN

    PubMed Central

    Benfey, Philip N.

    2015-01-01

    The quest to determine the genetic basis of root system architecture (RSA) has been greatly facilitated by recent developments in root phenotyping techniques. Methods that are accurate, high throughput, and control for environmental factors are especially attractive for quantitative trait locus mapping. Here, we describe the adaptation of a nondestructive in vivo gel-based root imaging platform for use in maize (Zea mays). We identify a large number of contrasting RSA traits among 25 founder lines of the maize nested association mapping population and locate 102 quantitative trait loci using the B73 (compact RSA) × Ki3 (exploratory RSA) mapping population. Our results suggest that a phenotypic tradeoff exists between small, compact RSA and large, exploratory RSA. PMID:25673779

  1. 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

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

    PubMed

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

    2007-01-01

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

  3. The polled locus maps to BTA1 in a Bos indicus x Bos taurus cross.

    PubMed

    Brenneman, R A; Davis, S K; Sanders, J O; Burns, B M; Wheeler, T C; Turner, J W; Taylor, J F

    1996-01-01

    Two hundred and nine reciprocal backcross and F2 progeny produced by embryo transfer from Angus (Bos taurus) and Brahman (Bos indicus) parents and their 60 parents and grandparents were utilized to localize the locus (POLL) responsible for the polled phenotype in a genetic map of bovine chromosome 1. Progeny were scored for polled, scurred, and horned phenotypes at 1 year of age and again following skull disection at slaughter at 20 months of age. Phenotype frequencies were independent of gender. One hundred and forty-two informative meioses for POLL and 13 microsatellite loci with an average of 267 informative meioses per locus contributed to a genetic map spanning 124.6 cM with an average interval of 9.6 cM. POLL mapped proximal to the centromere and 4.9 cM from TGLA49 supporting a previous study that employed two anonymous microsatellites. Difficulties in discriminating between scurred and horned phenotypes indicate that bracketing markers will be essential for refining the model for inheritance of the horned, scurred, and polled phenotypes and for effective marker assisted selection (MAS) for polled. PMID:8830095

  4. A cDNA encoding tyrosinase-related protein maps to the brown locus in mouse.

    PubMed Central

    Jackson, I J

    1988-01-01

    A mouse melanoma cDNA clone was isolated by virtue of its reactivity with two antisera raised against tyrosinase (EC 1.14.18.1) from two species, hamster and mouse. The cDNA (5A) cross-hybridizes with another, pMT4 [Shibahara, S., Tomita, V., Sakakura, T., Nager, C., Bhabatosh, C. & Muller, R. (1986) Nucleic Acids Res. 14, 2413-2427], previously thought to encode mouse tyrosinase. Two other cDNAs, one human and one mouse, have been reported recently [Kwon, B. S., Haq, A. K., Pomerantz, S. H. & Halaban, R. (1987) Proc. Natl. Acad. Sci. USA 84, 7473-7477; and Yamamoto, H., Takeuchi, S., Kudo, T., Makino, K., Nakata, A., Shinoda, T. & Takeuchi, T. (1987) Jpn. J. Genet. 62, 271-277] as candidates for tyrosinase, and they map at or very close to the mouse albino (c) locus. The proteins they encode are very similar to each other but are distinct from (although related to) the pMT4-encoded protein. Here I use recombinant inbred strains to localize pMT4 at or close to the mouse brown (b) locus. I suggest that the gene mapping to c is the authentic tyrosinase gene, whereas that mapping to b encodes a tyrosinase-related protein. All b mutations in laboratory strains are associated with the same diagnostic Taq I fragment, suggesting that all derive from the same original mutation. I discuss possible function(s) of the tyrosinase-related protein. Images PMID:3132713

  5. 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.

  6. Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant

    PubMed Central

    Almeida, Rodrigo; Ricaño-Ponce, Isis; Kumar, Vinod; Deelen, Patrick; Szperl, Agata; Trynka, Gosia; Gutierrez-Achury, Javier; Kanterakis, Alexandros; Westra, Harm-Jan; Franke, Lude; Swertz, Morris A.; Platteel, Mathieu; Bilbao, Jose Ramon; Barisani, Donatella; Greco, Luigi; Mearin, Luisa; Wolters, Victorien M.; Mulder, Chris; Mazzilli, Maria Cristina; Sood, Ajit; Cukrowska, Bozena; Núñez, Concepción; Pratesi, Riccardo; Withoff, Sebo; Wijmenga, Cisca

    2014-01-01

    Using the Immunochip for genotyping, we identified 39 non-human leukocyte antigen (non-HLA) loci associated to celiac disease (CeD), an immune-mediated disease with a worldwide frequency of ∼1%. The most significant non-HLA signal mapped to the intronic region of 70 kb in the LPP gene. Our aim was to fine map and identify possible functional variants in the LPP locus. We performed a meta-analysis in a cohort of 25 169 individuals from six different populations previously genotyped using Immunochip. Imputation using data from the Genome of the Netherlands and 1000 Genomes projects, followed by meta-analysis, confirmed the strong association signal on the LPP locus (rs2030519, P = 1.79 × 10−49), without any novel associations. The conditional analysis on this top SNP-indicated association to a single common haplotype. By performing haplotype analyses in each population separately, as well as in a combined group of the four populations that reach the significant threshold after correction (P < 0.008), we narrowed down the CeD-associated region from 70 to 2.8 kb (P = 1.35 × 10−44). By intersecting regulatory data from the ENCODE project, we found a functional SNP, rs4686484 (P = 3.12 × 10−49), that maps to several B-cell enhancer elements and a highly conserved region. This SNP was also predicted to change the binding motif of the transcription factors IRF4, IRF11, Nkx2.7 and Nkx2.9, suggesting its role in transcriptional regulation. We later found significantly low levels of LPP mRNA in CeD biopsies compared with controls, thus our results suggest that rs4686484 is the functional variant in this locus, while LPP expression is decreased in CeD. PMID:24334606

  7. 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. PMID:22497221

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

    SciTech Connect

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

    1994-01-01

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

  9. 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

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

    PubMed

    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

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

    PubMed

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

    2007-02-01

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

  12. 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.

  13. 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.

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

    SciTech Connect

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

    1995-07-20

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

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

    PubMed

    Lieto, L D; Cothran, E G

    2003-01-01

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

  16. A genome‐wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain

    PubMed Central

    Deshmukh, H.A.; van Zuydam, N.R.; Liu, Y.; Donnelly, L.A.; Zhou, K.; Morris, A.D.; Colhoun, H.M.; Palmer, C.N.A.; Smith, B.H.

    2015-01-01

    Abstract Background Neuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population. Method We accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non‐genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets. Results After data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p‐value of 1.77 × 10−7 at rs17428041. The narrow‐sense heritability of this phenotype was 11.00%. Conclusion This genome‐wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level. PMID:24974787

  17. 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.

  18. 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

  19. On the Components of Segregation Distortion in DROSOPHILA MELANOGASTER. II. Deletion Mapping and Dosage Analysis of the SD Locus

    PubMed Central

    Brittnacher, John G.; Ganetzky, Barry

    1983-01-01

    Segregation distorter (SD) chromosomes are preferentially transmitted to offspring from heterozygous SD/SD+ males owing to the induced dysfunction of the SD+-bearing sperm. This phenomenon involves at least two major loci: the Sd locus whose presence is necessary for distortion to occur and the Rsp locus which acts as the site of Sd action. Several additional loci on SD chromosomes enhance distortion.—In a previous study deletions were used to map the Sd locus and to determine some of its properties. We have extended this analysis with the isolation and characterization of 14 new deletions in the Sd region. From our results we conclude (1) SD chromosomes contain a single Sd locus located in region 37D2-6 of the salivary gland chromosome map. Deletion of this locus in any of three SD chromosomes now studied results in complete loss of ability to distort a sensitive chromosome; (2) the reduced male fecundity observed in many homozygous SD or SDi/SDj combinations is due at least in part to the action of the Sd locus. The fecundity of these males can be substantially increased by deletion of one Sd locus. Thus, it is the presence of two doses of Sd rather than the absence of Sd+ that produces the lowered male fecundity in SD homozygotes; (3) Sd behaves as a neomorph, whereas Sd+, if it exists at all, is amorphic with respect to segregation distortion; (4) these results support a model in which the Sd product is made in limiting amounts and the interaction of this product with the Rsp locus causes sperm dysfunction. The Sd product appears to act preferentially at Rsps (sensitive-Responder) but may also act at Rspi (insensitive-Responder). PMID:17246120

  20. 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.

  1. 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

  2. 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.

  3. 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. PMID:27556229

  4. 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

  5. High-resolution linkage map in the vicinity of the Lp locus

    SciTech Connect

    Mullick, A.; Gros, P.; Trasler, D.

    1995-04-10

    Looptail (Lp) is a mutation that profoundly affects neurulation in mouse and is characterized by craniorachischisis, an open neural tube extending from the midbrain to the tail in embryos homozygous for the mutation. Lp maps to the distal portion of mouse chromosome 1, and as part of a positional cloning approach, we have generated a high-resolution linkage map of the Lp chromosomal region. For this, we have carried out extensive segregation analysis in a total of 706 backcross mice informative for Lp and derived from two crosses, (Lp/ + X SJL/J)F1 X SJL/J and (Lp/ + X SWR/J)F1 X SWR/J. In addition, 269 mice from a (Mus spretus X C57BL/6J)F1 X C57BL/6J interspecific backcross were also used to order marker loci and calculate intergene distances for this region. With these mice, a total of 28 DNA markers corresponding to either cloned genes or anonymous markers of the SSLP or SSCP-types were mapped within a 5-cM interval overlapping the Lp region, with the following locus order and interlocus distances (in cM): centromere-D1Mit110 / Atp1{beta}1 / Cd3{zeta} /Cd3{eta} / D1Mit145 - D1Hun14 /D1Mit15 - D1Mit111 / D1Mit112 - D1Mit114 - D1Mit148 / D1Mit205/ D1Mit36 / D1Mit146 / D1Mit147 / D1Mit149 / Spnal1/Fcer1{alpha}-Eph1-Hlx1/D1Mit62. These studies have allowed the delineation of a maximum genetic interval for Lp of 0.5 cM, a size amenable to physical mapping techniques. 58 refs., 4 figs., 2 tabs.

  6. Functional Multi-Locus QTL Mapping of Temporal Trends in Scots Pine Wood Traits

    PubMed Central

    Li, Zitong; Hallingbäck, Henrik R.; Abrahamsson, Sara; Fries, Anders; Gull, Bengt Andersson; Sillanpää, Mikko J.; García-Gil, M. Rosario

    2014-01-01

    Quantitative trait loci (QTL) mapping of wood properties in conifer species has focused on single time point measurements or on trait means based on heterogeneous wood samples (e.g., increment cores), thus ignoring systematic within-tree trends. In this study, functional QTL mapping was performed for a set of important wood properties in increment cores from a 17-yr-old Scots pine (Pinus sylvestris L.) full-sib family with the aim of detecting wood trait QTL for general intercepts (means) and for linear slopes by increasing cambial age. Two multi-locus functional QTL analysis approaches were proposed and their performances were compared on trait datasets comprising 2 to 9 time points, 91 to 455 individual tree measurements and genotype datasets of amplified length polymorphisms (AFLP), and single nucleotide polymorphism (SNP) markers. The first method was a multilevel LASSO analysis whereby trend parameter estimation and QTL mapping were conducted consecutively; the second method was our Bayesian linear mixed model whereby trends and underlying genetic effects were estimated simultaneously. We also compared several different hypothesis testing methods under either the LASSO or the Bayesian framework to perform QTL inference. In total, five and four significant QTL were observed for the intercepts and slopes, respectively, across wood traits such as earlywood percentage, wood density, radial fiberwidth, and spiral grain angle. Four of these QTL were represented by candidate gene SNPs, thus providing promising targets for future research in QTL mapping and molecular function. Bayesian and LASSO methods both detected similar sets of QTL given datasets that comprised large numbers of individuals. PMID:25305041

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

    PubMed

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

    1998-08-01

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

  8. Quantitative Trait Locus Mapping of Melanization in the Plant Pathogenic Fungus Zymoseptoria tritici

    PubMed Central

    Lendenmann, Mark H.; Croll, Daniel; Stewart, Ethan L.; McDonald, Bruce A.

    2014-01-01

    Melanin plays an important role in virulence and antimicrobial resistance in several fungal pathogens. The wheat pathogen Zymoseptoria tritici is important worldwide, but little is known about the genetic architecture of pathogenicity, including the production of melanin. Because melanin production can exhibit complex inheritance, we used quantitative trait locus (QTL) mapping in two crosses to identify the underlying genes. Restriction site−associated DNA sequencing was used to genotype 263 (cross 1) and 261 (cross 2) progeny at ~8500 single-nucleotide polymorphisms and construct two dense linkage maps. We measured gray values, representing degrees of melanization, for single-spore colonies growing on Petri dishes by using a novel image-processing approach that enabled high-throughput phenotyping. Because melanin production can be affected by stress, each offspring was grown in two stressful environments and one control environment. We detected six significant QTL in cross 1 and nine in cross 2, with three QTL shared between the crosses. Different QTL were identified in different environments and at different colony ages. By obtaining complete genome sequences for the four parents and analyzing sequence variation in the QTL confidence intervals, we identified 16 candidate genes likely to affect melanization. One of these candidates was PKS1, a polyketide synthase gene known to play a role in the synthesis of dihydroxynaphthalene melanin. Three candidate quantitative trait nucleotides were identified in PKS1. Many of the other candidate genes were not previously associated with melanization. PMID:25360032

  9. 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.

  10. 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. PMID:26959315

  11. 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.

  12. 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

  13. 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

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

    PubMed Central

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

    1995-01-01

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

  15. 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

  16. High-density genetic map construction and identification of a locus controlling weeping trait in an ornamental woody plant (Prunus mume Sieb. et Zucc)

    PubMed Central

    Zhang, Jie; Zhang, Qixiang; Cheng, Tangren; Yang, Weiru; Pan, Huitang; Zhong, Junjun; Huang, Long; Liu, Enze

    2015-01-01

    High-density genetic map is a valuable tool for fine mapping locus controlling a specific trait especially for perennial woody plants. In this study, we firstly constructed a high-density genetic map of mei (Prunus mume) using SLAF markers, developed by specific locus amplified fragment sequencing (SLAF-seq). The linkage map contains 8,007 markers, with a mean marker distance of 0.195 cM, making it the densest genetic map for the genus Prunus. Though weeping trees are used worldwide as landscape plants, little is known about weeping controlling gene(s) (Pl). To test the utility of the high-density genetic map, we did fine-scale mapping of this important ornamental trait. In total, three statistic methods were performed progressively based on the result of inheritance analysis. Quantitative trait loci (QTL) analysis initially revealed that a locus on linkage group 7 was strongly responsible for weeping trait. Mutmap-like strategy and extreme linkage analysis were then applied to fine map this locus within 1.14 cM. Bioinformatics analysis of the locus identified some candidate genes. The successful localization of weeping trait strongly indicates that the high-density map constructed using SLAF markers is a worthy reference for mapping important traits for woody plants. PMID:25776277

  17. High-density genetic map construction and identification of a locus controlling weeping trait in an ornamental woody plant (Prunus mume Sieb. et Zucc).

    PubMed

    Zhang, Jie; Zhang, Qixiang; Cheng, Tangren; Yang, Weiru; Pan, Huitang; Zhong, Junjun; Huang, Long; Liu, Enze

    2015-06-01

    High-density genetic map is a valuable tool for fine mapping locus controlling a specific trait especially for perennial woody plants. In this study, we firstly constructed a high-density genetic map of mei (Prunus mume) using SLAF markers, developed by specific locus amplified fragment sequencing (SLAF-seq). The linkage map contains 8,007 markers, with a mean marker distance of 0.195 cM, making it the densest genetic map for the genus Prunus. Though weeping trees are used worldwide as landscape plants, little is known about weeping controlling gene(s) (Pl). To test the utility of the high-density genetic map, we did fine-scale mapping of this important ornamental trait. In total, three statistic methods were performed progressively based on the result of inheritance analysis. Quantitative trait loci (QTL) analysis initially revealed that a locus on linkage group 7 was strongly responsible for weeping trait. Mutmap-like strategy and extreme linkage analysis were then applied to fine map this locus within 1.14 cM. Bioinformatics analysis of the locus identified some candidate genes. The successful localization of weeping trait strongly indicates that the high-density map constructed using SLAF markers is a worthy reference for mapping important traits for woody plants.

  18. Fine mapping of the FecL locus influencing prolificacy in Lacaune sheep.

    PubMed

    Drouilhet, L; Lecerf, F; Bodin, L; Fabre, S; Mulsant, P

    2009-12-01

    In the Lacaune sheep population, two major loci influencing ovulation rate are segregating: FecX and FecL. The FecX(L) mutation is a non-conservative substitution (p.Cys53Tyr) in BMP15 that prevents the processing of the protein. Using a statistical approach, FecL has been shown to be an autosomal major gene. A full genome scan localized the FecL locus on sheep chromosome 11. Fine mapping reduced the interval containing FecL to markers BM17132 and FAM117A, corresponding to a synteny block of 1.1 megabases on human chromosome 17, which encompasses 20 genes. The expression of 16 genes from this interval was observed in tissues of the reproductive axis, but expression was not affected in homozygous FecL(L) females. In this interval, a unique haplotype was associated with the FecL(L) mutation. This particular haplotype could be predicted by the DLX3:c.*803A>G SNP in the 3' UTR sequence of the DLX3 gene. This SNP provided accurate classification of animals (99.5%) as carriers or non-carriers of the mutation and therefore maybe useful in marker assisted selection. A synergistic action of FecL(L) and FecX(L) mutations on both ovulation rate and litter size was demonstrated. Until now, all the Fec genes identified in sheep belong to the bone morphogenetic protein (BMP) system. Based on the human orthologous region, none of the 20 genes in the FecL region corresponds to known molecules in the BMP system. The identification of the FecL(L) mutation could lead to the discovery of a new pathway involved in the regulation of ovulation rate.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

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

    PubMed

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

    1987-04-01

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

  5. 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

  6. 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.

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

    PubMed Central

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

    2013-01-01

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

  8. Close mapping of the focal non-epidermolytic palmoplantar keratoderma (PPK) locus associated with oesophageal cancer (TOC).

    PubMed

    Kelsell, D P; Risk, J M; Leigh, I M; Stevens, H P; Ellis, A; Hennies, H C; Reis, A; Weissenbach, J; Bishop, D T; Spurr, N K; Field, J K

    1996-06-01

    Focal non-epidermolytic palmoplantar keratoderma (PPK or palmoplantar ectodermal dysplasia type III) is associated with oesophageal cancer in three families: two large pedigrees located in Liverpool, UK and in the midwestern American states and one smaller family from Germany. In these families, the PPK is inherited as autosomal dominant and has a late onset, usually manifesting between 7 and 8 years of age. The disease is characterised by thickening of the pressure areas of the soles, but is not restricted to the feet and also presents with oral leukokeratosis and follicular hyperkeratosis. The disease locus [previously termed the "tylosis oesophageal cancer gene' (TOC) locus] has been mapped to 17q23-qter by linkage analysis. This region is located telomeric to the keratin 16 gene, in which mutations have been identified in focal PPK families who show no increased cancer risk. We describe the close mapping of this locus to the interval between AFMb054zf9 and D17S1603 using haplotype analysis of additional Généthon markers in the region and show that although the American family is unlikely to be related to either of the other two, the UK and German pedigrees may share a common descent. This work provides a basis for positional cloning and candidate gene analysis in order to identify a gene that may be involved in familial oesophageal cancer.

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

    SciTech Connect

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

    1994-09-01

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

  10. 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

  11. 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

    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

  12. 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

    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.

  13. Identification and mapping of resistance gene analogs and a white rust resistance locus in Brassica rapa ssp. oleifera.

    PubMed

    Tanhuanpää, P

    2004-04-01

    The objective of this investigation was to tag a locus for white rust resistance in a Brassica rapa ssp. oleifera F(2) population segregating for this trait, using bulked segregant analysis with random amplified polymorphic DNA (RAPD) markers, linkage mapping and a candidate gene approach based on resistance gene analogs (RGAs). The resistance source was the Finnish line Bor4109. The reaction against white rust races 7a and 7v was scored in 20 seedlings from each self-pollinated F(2 )individual. The proportion of resistant plants among these F(3) families varied from 0 to 67%. Bulked segregant analysis did not reveal any markers linked with resistance and, therefore, a linkage map with 81 markers was created. A locus that accounted for 18.4% of the variation in resistance to white rust was mapped to linkage group (LG) 2 near the RAPD marker Z19a. During the study, a bacterial resistance gene homologous to Arabidopsis RPS2 and six different RGAs were sequenced. RPS2 and five of the RGAs were mapped to linkage groups LG1, LG4 and LG9. Unfortunately, none of the RGAs could be shown to be associated with white rust resistance.

  14. Mapping of deletion breakpoints at the CDKN2A locus in melanoma: detection of MTAP-ANRIL fusion transcripts.

    PubMed

    Xie, Huaping; Rachakonda, P Sivaramakrishna; Heidenreich, Barbara; Nagore, Eduardo; Sucker, Antje; Hemminki, Kari; Schadendorf, Dirk; Kumar, Rajiv

    2016-03-29

    Genomic locus at chromosome 9p21 that contains the CDKN2A and CDKN2B tumor suppressor genes is inactivated through mutations, deletions and promoter methylation in multiple human cancers. Additionally, the locus encodes an anti-sense RNA (ANRIL). Both hemizygous and homozygous deletions at the locus targeting multiple genes are fairly common in different cancers. We in this study investigated breakpoints in five melanoma cell lines, derived from metastasized tumors, with previously identified homozygous deletions using array comparative genomic hybridization (aCGH). For breakpoint mapping, we used primer approximation multiplex PCR (PAMP) and inverse PCR techniques. Our results showed that three cell lines carried complex rearrangements. In two other cell lines, with focal deletions of 141 kb and 181 kb, we identified fusion gene products, involving MTAP and ANRIL. We also confirmed the complex rearrangements and focal deletions in DNA from tumor tissues corresponding to three cell lines. The rapid amplification of 3'cDNA ends (3'RACE) carried out on transcripts resulted in identification of three isoforms of MTAP-ANRIL fusion gene. Screening of cDNA from 64 melanoma cell lines resulted in detection of fusion transcripts in 13 (20%) cell lines that involved exons 4-7 of the MTAP and exon 2 or 5 of the ANRIL genes. We also detected fusion transcripts involving MTAP and ANRIL in two of the seven primary melanoma tumors with focal deletion at the locus. The results from the study, besides identifying complex rearrangements involving CDKN2A locus, show frequent occurrence of fusion transcripts involving MTAP and ANRIL genes. PMID:26909863

  15. Identification and mapping of a major dominant quantitative trait locus controlling seeds per silique as a single Mendelian factor in Brassica napus L.

    PubMed

    Zhang, Liwu; Li, Shipeng; Chen, Lei; Yang, Guangsheng

    2012-08-01

    One putative quantitative trait locus (QTL) for seeds per silique (SS), cqSS.A8, was identified using a double haploid (DH) population in Brassica napus, and near-isogenic lines (NILs; BC(3)F(1)) for cqSS.A8 were developed. However, the flanking markers from cqSS.A8 showed no significant difference using single-marker analysis, even though the frequency distribution of SS in the BC(3)F(1) was bimodal, suggesting that one novel locus existed. In this study, we characterized the effects of this locus in the NILs and used a published linkage map to determine its location. A three-step approach was designed for mapping the locus in the NILs (BC(3)F(2)): (1) determining the individual BC(3)F(2) genotype at the locus using a progeny test; (2) identifying amplified fragment length polymorphism (AFLP) markers linked to the locus using a combination of AFLP and bulked segregant analysis; and (3) determining the location and effects of this locus. QTL analysis in the BC(3)F(2) revealed that this locus explained 85.8 and 55.7 % of phenotypic variance for SS and SL, respectively. Its additive and dominant effects on SS were 6.1 and 5.7, respectively. The locus was validated using a DH population by composite interval mapping and located to linkage group C9 (designated as qSS.C9). Mapping qSS.C9 was undertaken using 230 extremely low-SS plants of a BC(4)F(1) population containing 807 plants. We found that qSS.C9 delimited a 1.005-Mb interval including 218 predicted genes in the reference Brassica rapa (Chiifu-401). These results will greatly facilitate map-based cloning of qSS.C9 and seed yield improvement in rapeseed.

  16. 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

  17. 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

  18. 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.

  19. 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. PMID:25378557

  20. 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.

  1. Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus.

    PubMed Central

    Miller, R D; Hogg, J; Ozaki, J H; Gell, D; Jackson, S P; Riblet, R

    1995-01-01

    The gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) has been proposed recently as a candidate gene for the mouse severe combined immune deficiency (scid) locus. We have used a partial cDNA clone for human DNA-PKcs to map the mouse homologue using a large interspecific backcross panel. We found that the mouse gene for DNA-PKcs does not recombine with scid, consistent with the hypothesis that scid is a mutation in the mouse gene for DNA-PKcs. Images Fig. 3 PMID:7479885

  2. 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

  3. 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

    2013-01-01

    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. PMID:27137386

  4. 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.

  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. 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.

  7. Exclusion mapping of the hereditary dentatorubropallidoluysian atrophy gene from the Huntington's disease locus.

    PubMed

    Kondo, I; Ohta, H; Yazaki, M; Ikeda, J E; Gusella, J F; Kanazawa, I

    1990-02-01

    Hereditary dentatorubropallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder. Clinical and genetic findings in hereditary DRPLA are very similar to those of Huntington's disease (HD). However, it can be differentiated from HD by the pathological findings of dentatorubral and pallidoluysian atrophies and by a lack of prominent atrophy of the striatum at necropsy. The hereditary DRPLA gene has not been localised and the possibility that the two disease loci are allelic has been suggested. We have searched for linkage between the locus for hereditary DRPLA and D4S10 using the G8 probe, which is a genetic marker linked to HD. In four families, there were negative scores at all recombination fractions and the lod score was -2.215 at recombination fraction theta = 0.15. These data indicate that the locus for hereditary DRPLA is not closely linked to D4S10 and that hereditary DRPLA is a distinct disease from HD.

  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. 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.

  10. A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species

    PubMed Central

    Freimer, Nelson B.; Service, Susan K.; Ophoff, Roel A.; Jasinska, Anna J.; McKee, Kevin; Villeneuve, Amelie; Belisle, Alexandre; Bailey, Julia N.; Breidenthal, Sherry E.; Jorgensen, Matthew J.; Mann, J. John; Cantor, Rita M.; Dewar, Ken; Fairbanks, Lynn A.

    2007-01-01

    Non-human primates (NHP) provide crucial research models. Their strong similarities to humans make them particularly valuable for understanding complex behavioral traits and brain structure and function. We report here the genetic mapping of an NHP nervous system biologic trait, the cerebrospinal fluid (CSF) concentration of the dopamine metabolite homovanillic acid (HVA), in an extended inbred vervet monkey (Chlorocebus aethiops sabaeus) pedigree. CSF HVA is an index of CNS dopamine activity, which is hypothesized to contribute substantially to behavioral variations in NHP and humans. For quantitative trait locus (QTL) mapping, we carried out a two-stage procedure. We first scanned the genome using a first-generation genetic map of short tandem repeat markers. Subsequently, using >100 SNPs within the most promising region identified by the genome scan, we mapped a QTL for CSF HVA at a genome-wide level of significance (peak logarithm of odds score >4) to a narrow well delineated interval (<10 Mb). The SNP discovery exploited conserved segments between human and rhesus macaque reference genome sequences. Our findings demonstrate the potential of using existing primate reference genome sequences for designing high-resolution genetic analyses applicable across a wide range of NHP species, including the many for which full genome sequences are not yet available. Leveraging genomic information from sequenced to nonsequenced species should enable the utilization of the full range of NHP diversity in behavior and disease susceptibility to determine the genetic basis of specific biological and behavioral traits. PMID:17884980

  11. 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

  12. Actin-binding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28

    SciTech Connect

    Gorlin, J.B. Dana-Farber Cancer Institute, Boston, MA ); Henske, E.; Hartwig, J.H.; Kwiatkowski, D.J. ); Warren, S.T.; Kunst, C.B. ); D'Urso, M.; Palmieri, G. ); Bruns, G. )

    1993-08-01

    Actin-binding protein-280 (ABP-280) is a dimeric actin filament-crosslinking protein that promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. The authors have mapped the ABP-280 filamin gene (FLN) to Xq28 by Southern blot analysis of somatic cell hybrid lines, by fluorescence in situ hybridization, and through identification of portions of the FLN gene within cosmids and YACs mapped to Xq28. The FLN gene is found within a 200-kb region centromeric to the G6PD locus and telomeric to DSX52 and the color vision locus. 23 refs., 2 figs.

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

    PubMed

    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

    2015-10-06

    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.

  14. 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.

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

    PubMed

    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

  16. 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

  17. A sequential quantitative trait locus fine-mapping strategy using recombinant-derived progeny.

    PubMed

    Yang, Qin; Zhang, Dongfeng; Xu, Mingliang

    2012-04-01

    A thorough understanding of the quantitative trait loci (QTLs) that underlie agronomically important traits in crops would greatly increase agricultural productivity. Although advances have been made in QTL cloning, the majority of QTLs remain unknown because of their low heritability and minor contributions to phenotypic performance. Here we summarize the key advantages and disadvantages of current QTL fine-mapping methodologies, and then introduce a sequential QTL fine-mapping strategy based on both genotypes and phenotypes of progeny derived from recombinants. With this mapping strategy, experimental errors could be dramatically diminished so as to reveal the authentic genetic effect of target QTLs. The number of progeny required to detect QTLs at various R2 values was calculated, and the backcross generation suitable to start QTL fine-mapping was also estimated. This mapping strategy has proved to be very powerful in narrowing down QTL regions, particularly minor-effect QTLs, as revealed by fine-mapping of various resistance QTLs in maize. Application of this sequential QTL mapping strategy should accelerate cloning of agronomically important QTLs, which is currently a substantial challenge in crops. PMID:22348858

  18. 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.

  19. 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.

  20. 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

  1. 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.

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

    SciTech Connect

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

    1995-12-01

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

  3. X-linked congenital ataxia: a new locus maps to Xq25-q27.1.

    PubMed

    Zanni, Ginevra; Bertini, Enrico; Bellcross, Cecelia; Nedelec, Brigitte; Froyen, Guy; Neuhäuser, Gerhard; Opitz, John M; Chelly, Jamel

    2008-03-01

    We report clinical and molecular studies on a large American family of Norwegian descent with X-linked nonprogressive congenital ataxia (XCA) in six affected males over three generations. Neuroimaging showed global cerebellar hypoplasia without evidence of supratentorial anomalies. Linkage analysis resulted in a maximum LOD score Z = 3.44 for marker DXS1192 at Theta = 0.0 with flanking markers DXS1047 and DXS1227 defining a region of 12 cM in Xq25-q27.1. The clinical and neuroradiological findings in the present family are very similar to those described in two reported X-linked families [Illarioshkin et al., 1996; Bertini et al., 2000]; however, the newly identified locus does not overlap with the one defined previously, indicating that there are at least two genes responsible for this rare form of X-linked congenital cerebellar ataxia with normal intelligence.

  4. 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

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

    SciTech Connect

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

    1995-01-01

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

  6. Large-Scale SNP Discovery and Genotyping for Constructing a High-Density Genetic Map of Tea Plant Using Specific-Locus Amplified Fragment Sequencing (SLAF-seq).

    PubMed

    Ma, Jian-Qiang; Huang, Long; Ma, Chun-Lei; Jin, Ji-Qiang; Li, Chun-Fang; Wang, Rong-Kai; Zheng, Hong-Kun; Yao, Ming-Zhe; Chen, Liang

    2015-01-01

    Genetic maps are important tools in plant genomics and breeding. The present study reports the large-scale discovery of single nucleotide polymorphisms (SNPs) for genetic map construction in tea plant. We developed a total of 6,042 valid SNP markers using specific-locus amplified fragment sequencing (SLAF-seq), and subsequently mapped them into the previous framework map. The final map contained 6,448 molecular markers, distributing on fifteen linkage groups corresponding to the number of tea plant chromosomes. The total map length was 3,965 cM, with an average inter-locus distance of 1.0 cM. This map is the first SNP-based reference map of tea plant, as well as the most saturated one developed to date. The SNP markers and map resources generated in this study provide a wealth of genetic information that can serve as a foundation for downstream genetic analyses, such as the fine mapping of quantitative trait loci (QTL), map-based cloning, marker-assisted selection, and anchoring of scaffolds to facilitate the process of whole genome sequencing projects for tea plant.

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

    PubMed

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

    1994-01-01

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

  8. HAPPY mapping of a YAC reveals alternative haplotypes in the human immunoglobulin VH locus.

    PubMed Central

    Walter, G; Tomlinson, I M; Cook, G P; Winter, G; Rabbitts, T H; Dear, P H

    1993-01-01

    We have identified and sequenced 14 human immunoglobulin VH segments cloned in a yeast artificial chromosome, and have used a rapid PCR-based technique (HAPPY mapping, 12) to derive the order and approximate distances between them. The sequences mapped comprise thirteen germline VH segments and one rearranged VH3 gene. Comparison of our map with other data suggests the existence of at least two distinct haplotypes, differing in the presence or absence of the consecutive genes DP-78, DP-46 and DP-64, and in the duplication of segments DP-49 and DP-65. Screening of ten individuals confirms the existence of both haplotypes, and indicates that both are common amongst the population. Images PMID:8233786

  9. 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.

  10. Mapping a new genetic locus for X linked retinitis pigmentosa to Xq28.

    PubMed

    Melamud, A; Shen, G-Q; Chung, D; Xi, Q; Simpson, E; Li, L; Peachey, N S; Zegarra, H; Hagstrom, S A; Wang, Q K; Traboulsi, E I

    2006-06-01

    We have defined a new genetic locus for an X linked form of retinitis pigmentosa (RP) on chromosome Xq28. We examined 15 members of a family in which RP appeared to be transmitted in an X linked manner. Ocular examinations were performed, and fundus photographs and electroretinograms were obtained for selected patients. Blood samples were obtained from all patients and an additional seven family members who were not given examinations. Visual acuity in four affected individuals ranged from 20/40 to 20/80+. Patients described the onset of night blindness and colour vision defects in the second decade of life, with the earliest at 13 years of age. Examined affected individuals had constricted visual fields and retinal findings compatible with RP. Based on full field electroretinography, cone function was more severely reduced than rod function. Female carriers had no ocular signs or symptoms and slightly reduced cone electroretinographic responses. Affected and non-affected family members were genotyped for 20 polymorphic markers on the X-chromosome spaced at 10 cM intervals. Genotyping data were analysed using GeneMapper software. Genotyping and linkage analyses identified significant linkage to markers DXS8061, DXS1073, and DXS1108 with two point LOD scores of 2.06, 2.17, and 2.20, respectively. Haplotype analysis revealed segregation of the disease phenotype with markers at Xq28. PMID:16740911

  11. Admixture mapping identifies a quantitative trait locus associated with FEV1/FVC in the COPDGene Study.

    PubMed

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

    2014-11-01

    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 3,300 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.

  12. Quantitative Trait Locus (QTL) Mapping Reveals a Role for Unstudied Genes in Aspergillus Virulence

    PubMed Central

    Christians, Julian K.; Cheema, Manjinder S.; Vergara, Ismael A.; Watt, Cortney A.; Pinto, Linda J.; Chen, Nansheng; Moore, Margo M.

    2011-01-01

    Infections caused by the fungus Aspergillus are a major cause of morbidity and mortality in immunocompromised populations. To identify genes required for virulence that could be used as targets for novel treatments, we mapped quantitative trait loci (QTL) affecting virulence in the progeny of a cross between two strains of A. nidulans (FGSC strains A4 and A91). We genotyped 61 progeny at 739 single nucleotide polymorphisms (SNP) spread throughout the genome, and constructed a linkage map that was largely consistent with the genomic sequence, with the exception of one potential inversion of ∼527 kb on Chromosome V. The estimated genome size was 3705 cM and the average intermarker spacing was 5.0 cM. The average ratio of physical distance to genetic distance was 8.1 kb/cM, which is similar to previous estimates, and variation in recombination rate was significantly positively correlated with GC content, a pattern seen in other taxa. To map QTL affecting virulence, we measured the ability of each progeny strain to kill model hosts, larvae of the wax moth Galleria mellonella. We detected three QTL affecting in vivo virulence that were distinct from QTL affecting in vitro growth, and mapped the virulence QTL to regions containing 7–24 genes, excluding genes with no sequence variation between the parental strains and genes with only synonymous SNPs. None of the genes in our QTL target regions have been previously associated with virulence in Aspergillus, and almost half of these genes are currently annotated as “hypothetical”. This study is the first to map QTL affecting the virulence of a fungal pathogen in an animal host, and our results illustrate the power of this approach to identify a short list of unknown genes for further investigation. PMID:21559404

  13. 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.

  14. Construction of a genetic map based on high-throughput SNP genotyping and genetic mapping of a TuMV resistance locus in Brassica rapa.

    PubMed

    Chung, Hee; Jeong, Young-Min; Mun, Jeong-Hwan; Lee, Soo-Seong; Chung, Won-Hyong; Yu, Hee-Ju

    2014-04-01

    Brassica rapa is a member of the Brassicaceae family and includes vegetables and oil crops that are cultivated worldwide. The introduction of durable resistance against turnip mosaic virus (TuMV) into agronomically important cultivars has been a significant challenge for genetic and horticultural breeding studies of B. rapa. Based on our previous genome-wide analysis of DNA polymorphisms between the TuMV-resistant doubled haploid (DH) line VC40 and the TuMV-susceptible DH line SR5, we constructed a core genetic map of the VCS-13M DH population, which is composed of 83 individuals derived from microspore cultures of a F1 cross between VC40 and SR5, by analyzing the segregation of 314 sequence-characterized genetic markers. The genetic markers correspond to 221 SNPs and 31 InDels of genes as well as 62 SSRs, covering 1,115.9 cM with an average distance of 3.6 cM between the adjacent marker loci. The alignment and orientation of the constructed map showed good agreement with the draft genome sequence of Chiifu, thus providing an efficient strategy to map genic sequences. Using the genetic map, a novel dominant TuMV resistance locus (TuMV-R) in the VCS-13M DH population was identified as a 0.34 Mb region in the short arm of chromosome A6 in which four CC-NBS-LRR resistance genes and two pathogenesis-related-1 genes reside. The genetic map developed in this study can play an important role in the genetic study of TuMV resistance and the molecular breeding of B. rapa.

  15. Construction of a genetic map based on high-throughput SNP genotyping and genetic mapping of a TuMV resistance locus in Brassica rapa.

    PubMed

    Chung, Hee; Jeong, Young-Min; Mun, Jeong-Hwan; Lee, Soo-Seong; Chung, Won-Hyong; Yu, Hee-Ju

    2014-04-01

    Brassica rapa is a member of the Brassicaceae family and includes vegetables and oil crops that are cultivated worldwide. The introduction of durable resistance against turnip mosaic virus (TuMV) into agronomically important cultivars has been a significant challenge for genetic and horticultural breeding studies of B. rapa. Based on our previous genome-wide analysis of DNA polymorphisms between the TuMV-resistant doubled haploid (DH) line VC40 and the TuMV-susceptible DH line SR5, we constructed a core genetic map of the VCS-13M DH population, which is composed of 83 individuals derived from microspore cultures of a F1 cross between VC40 and SR5, by analyzing the segregation of 314 sequence-characterized genetic markers. The genetic markers correspond to 221 SNPs and 31 InDels of genes as well as 62 SSRs, covering 1,115.9 cM with an average distance of 3.6 cM between the adjacent marker loci. The alignment and orientation of the constructed map showed good agreement with the draft genome sequence of Chiifu, thus providing an efficient strategy to map genic sequences. Using the genetic map, a novel dominant TuMV resistance locus (TuMV-R) in the VCS-13M DH population was identified as a 0.34 Mb region in the short arm of chromosome A6 in which four CC-NBS-LRR resistance genes and two pathogenesis-related-1 genes reside. The genetic map developed in this study can play an important role in the genetic study of TuMV resistance and the molecular breeding of B. rapa. PMID:24326528

  16. 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. PMID:12893462

  17. 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.

  18. 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.

  19. A linkage map of 10 loci flanking the Marfan syndrome locus on 15q: results of an International Consortium study.

    PubMed Central

    Sarfarazi, M; Tsipouras, P; Del Mastro, R; Kilpatrick, M; Farndon, P; Boxer, M; Bridges, A; Boileau, C; Junien, C; Hayward, C

    1992-01-01

    Members of an International Consortium for Linkage Analysis of the Marfan Syndrome (MFS1) have pooled data for joint analysis in an attempt to determine the precise location of the MFS1 gene and the order of 10 DNA markers on 15q. Five laboratories performed a total of 2111 genotypes in 22 families consisting of 225 affected and 248 normal subjects. For each marker a mean of 98 meioses was informative. D15S48 and D15S1 were identified as the closest linked markers with 99% upper confidence intervals of 12% and 13% respectively. We have used the CRI-MAP program to construct the most likely order as: D15S24-D15S25-D15S1-MFS1-D15S48-D15S49+ ++-(D15S45/S51)-(D15S29/S38). Placement of D15S2 in relation to -D15S1-D15S48- cannot be determined with certainty. The genetic map of these markers extends 53.6 cM in males and 65.0 cM in females with a sex averaged map of 60.7 cM. The sex difference was statistically significant (p = 0.005). Linkage heterogeneity between 22 MFS1 families was documented (p = 0.009) necessitating the exclusion of one family from the analysis. However, comparison of the remaining 21 families for two point and multipoint lod scores showed no evidence for linkage heterogeneity of the MFS1 locus. PMID:1613769

  20. 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.

  1. Identification and map location of TTR1, a single locus in Arabidopsis thaliana that confers tolerance to tobacco ringspot nepovirus.

    PubMed

    Lee, J M; Hartman, G L; Domier, L L; Bent, A F

    1996-11-01

    The interaction between Arabidopsis and the nepovirus tobacco ringspot virus (TRSV) was characterized. Of 97 Arabidopsis lines tested, all were susceptible when inoculated with TRSV grape strain. Even though there was systemic spread of the virs, there was a large degree of variation in symptoms as the most sensitive lines died 10 days after inoculation, while the most tolerant lines either were symptomless or developed only mild symptoms. Four lines were selected for further study based on their differential reactions to TRSV. Infected plants of line Col-0 and Col-0 gl1 flowered and produced seeds like noninfected plants, while those of lines Estland and H55 died before producing seeds. Symptoms appeared on sensitive plants approximately 5 to 6 days after inoculation. Serological studies indicated that in mechanically inoculated seedlings, the virus, as measured by coat protein accumulation, developed at essentially the same rates and to the same levels in each of the four lines, demonstrating that differences in symptom development were not due to a suppression of virus accumulation. Two additional TRSV strains gave similar results when inoculated on the four lines. Genetic studies with these four Arabidopsis lines revealed segregation of a single incompletely dominant locus controlling tolerance to TRSV grape strain. We have designated this locus TTR1. By using SSLP and CAPS markers, TTR1 was mapped to chromosome V near the nga129 marker. Seed transmission frequency of TRSV for Col-0 and Col-0 gl1 was over 95% and their progeny from crosses all had seed transmission frequencies of over 83%, which made it possible to evaluate the segregation of TTR1 in F2 progeny from infected F1 plants without inoculating F2 plants. Seed transmission of TRSV will be further exploited to streamline selection of individuals for fine mapping the TTR1 gene. The identification of tolerant and sensitive interactions between TRSV and A. thaliana lines provides a model system for

  2. 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.

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

    PubMed Central

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

    2000-01-01

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

  4. 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.

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

    PubMed

    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

  6. 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

  7. 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.

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

    PubMed Central

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

    1998-01-01

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

  9. 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.

  10. A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1-p13.3.

    PubMed

    Uyguner, O; Kayserili, H; Li, Y; Karaman, B; Nürnberg, G; Hennies, Hc; Becker, C; Nürnberg, P; Başaran, S; Apak, M Y; Wollnik, B

    2007-03-01

    Autosomal recessive inheritance of non-syndromic mental retardation (ARNSMR) may account for approximately 25% of all patients with non-specific mental retardation (NSMR). Although many X-linked genes have been identified as a cause of NSMR, only three autosomal genes are known to cause ARNSMR. We present here a large consanguineous Turkish family with four mentally retarded individuals from different branches of the family. Clinical tests showed cognitive impairment but no neurological, skeletal, and biochemical involvements. Genome-wide mapping using Human Mapping 10K Array showed a single positive locus with a parametric LOD score of 4.92 in a region on chromosome 1p21.1-p13.3. Further analyses using polymorphic microsatellite markers defined a 6.6-Mb critical region containing approximately 130 known genes. This locus is the fourth one linked to ARNSMR.

  11. 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

  12. Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis

    PubMed Central

    Kim, Kwangwoo; Bang, So-Young; Ikari, Katsunori; Yoo, Dae Hyun; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Kang, Young Mo; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Kim, Seong-Kyu; Choe, Jung-Yoon; Momohara, Shigeki; Taniguchi, Atsuo; Yamanaka, Hisashi; Nath, Swapan K.; Lee, Hye-Soon; Bae, Sang-Cheol

    2016-01-01

    Considerable sharing of disease alleles among populations is well-characterized in autoimmune disorders (e.g., rheumatoid arthritis), but there are some exceptional loci showing heterogenic association among populations. Here we investigated genetic variants with distinct effects on the development of rheumatoid arthritis in Asian and European populations. Ancestry-related association heterogeneity was examined using Cochran’s homogeneity tests for the disease association data from large Asian (n = 14,465; 9,299 discovery subjects and 5,166 validation subjects; 4 collections) and European (n = 45,790; 11 collections) rheumatoid arthritis case-control cohorts with Immunochip and genome-wide SNP array data. We identified significant heterogeneity between the two ancestries for the common variants in the GTF2I locus (PHeterogeneity = 9.6 × 10−9 at rs73366469) and showed that this heterogeneity was due to an Asian-specific association effect (ORMeta = 1.37 and PMeta = 4.2 × 10−13 in Asians; ORMeta = 1.00 and PMeta = 1.00 in Europeans). Trans-ancestral comparison and bioinfomatics analysis revealed a plausibly causal or disease-variant-tagging SNP (rs117026326; in linkage disequilibrium with rs73366469), whose minor allele is common in Asians but rare in Europeans. In conclusion, we identified largest-ever effect on Asian rheumatoid arthritis across human non-HLA regions at GTF2I by heterogeneity mapping followed by replication studies, and pinpointed a possible causal variant. PMID:27272985

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

    PubMed Central

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

    2016-01-01

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

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

    SciTech Connect

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

    1994-06-01

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

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

    SciTech Connect

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

    1994-07-01

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

  16. 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.

  17. 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.

  18. 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.

  19. High-Resolution Linkage and Quantitative Trait Locus Mapping Aided by Genome Survey Sequencing: Building Up An Integrative Genomic Framework for a Bivalve Mollusc

    PubMed Central

    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

    2014-01-01

    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. PMID:24107803

  20. 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.

  1. 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.

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

    SciTech Connect

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

    1993-04-01

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

  3. 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.

  4. 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. PMID:22382487

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  6. High-resolution mapping of Rsn1, a locus controlling sensitivity of rice to a necrosis-inducing phytotoxin from Rhizoctonia solani AG1-IA.

    PubMed

    Costanzo, Stefano; Jackson, Aaron K; Brooks, Steven A

    2011-06-01

    Rhizoctonia solani is a necrotrophic fungal pathogen that causes disease on many crop-plant species. Anastomosis group 1-IA is the causal agent of sheath blight of rice (Oryza sativa L.), one of the most important rice diseases worldwide. R. solani AG1-IA produces a necrosis-inducing phytotoxin and rice cultivar's sensitivity to the toxin correlates with disease susceptibility. Unlike genetic analyses of sheath blight resistance where resistance loci have been reported as quantitative trait loci, phytotoxin sensitivity is inherited as a Mendelian trait that permits high-resolution mapping of the sensitivity genes. An F(2) mapping population derived from parent cultivars 'Cypress' (toxin sensitive) and 'Jasmine 85' (toxin insensitive) was used to map Rsn1, the necrosis-inducing locus. Initial mapping based on 176 F(2) progeny and 69 simple sequence repeat (SSR) markers located Rsn1 on the long arm of chromosome 7, with tight linkage to SSR marker RM418. A high-resolution genetic map of the region was subsequently developed using a total of 1,043 F(2) progeny, and Rsn1 was mapped to a 0.7 cM interval flanked by markers NM590 and RM418. Analysis of the corresponding 29 Kb genomic sequences from reference cultivars 'Nipponbare' and '93-11' revealed the presence of four putative genes within the interval. Two are expressed cytokinin-O-glucosyltransferases, which fit an apoptotic pathway model of toxin activity, and are individually being investigated further as potential candidates for Rsn1.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Admixture Mapping of White Cell Count: Genetic Locus Responsible for Lower White Blood Cell Count in the Health ABC and Jackson Heart Studies

    PubMed Central

    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 ≥ 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 ∼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. PMID:18179887

  13. 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. PMID:16674556

  14. Combined linkage and association mapping reveals candidates for Scmv1, a major locus involved in resistance to sugarcane mosaic virus (SCMV) in maize

    PubMed Central

    2013-01-01

    Background Sugarcane mosaic virus (SCMV) disease causes substantial losses of grain yield and forage biomass in susceptible maize cultivars. Maize resistance to SCMV is associated with two dominant genes, Scmv1 and Scmv2, which are located on the short arm of chromosome 6 and near the centromere region of chromosome 3, respectively. We combined both linkage and association mapping to identify positional candidate genes for Scmv1. Results Scmv1 was fine-mapped in a segregating population derived from near-isogenic lines and further validated and fine-mapped using two recombinant inbred line populations. The combined results assigned the Scmv1 locus to a 59.21-kb interval, and candidate genes within this region were predicted based on the publicly available B73 sequence. None of three predicted genes that are possibly involved in the disease resistance response are similar to receptor-like resistance genes. Candidate gene–based association mapping was conducted using a panel of 94 inbred lines with variable resistance to SCMV. A presence/absence variation (PAV) in the Scmv1 region and two polymorphic sites around the Zmtrx-h gene were significantly associated with SCMV resistance. Conclusion Combined linkage and association mapping pinpoints Zmtrx-h as the most likely positional candidate gene for Scmv1. These results pave the way towards cloning of Scmv1 and facilitate marker-assisted selection for potyvirus resistance in maize. PMID:24134222

  15. 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.

  16. 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. PMID:26965508

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

    PubMed Central

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

    2010-01-01

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

  18. 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.

  19. 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

  20. 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.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    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

    1999-06-01

    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.

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

    PubMed

    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.

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

    PubMed

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

    2006-10-01

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

  5. 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

  6. 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.

  7. 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.

  8. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2006-10-01

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

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

    PubMed

    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

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

    SciTech Connect

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

    1993-05-01

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

  13. Transcriptomics-assisted quantitative trait locus fine mapping for the rapid identification of a nodulin 26-like intrinsic protein gene regulating boron efficiency in allotetraploid rapeseed.

    PubMed

    Hua, Yingpeng; Zhang, Didi; Zhou, Ting; He, Mingliang; Ding, Guangda; Shi, Lei; Xu, Fangsen

    2016-07-01

    Allotetraploid rapeseed (Brassica napus L., An An Cn Cn , 2n = 4x = 38) is extraordinarily susceptible to boron (B) deficiency, a ubiquitous problem causing severe losses in seed yield. The breeding of B-efficient rapeseed germ plasm is a cost-effective and environmentally friendly strategy for the agricultural industry; however, genes regulating B efficiency in allotetraploid rapeseed have not yet been isolated. In this research, quantitative trait locus (QTL) fine mapping and digital gene expression (DGE) profiling were combined to identify the candidate genes underlying the major-effect QTL qBEC-A3a, which regulates B efficiency. Comparative phenotype analyses of the near-isogenic lines (NILs) indicated that qBEC-A3a plays a significant role in improving B efficiency under B deficiency. Exploiting QTL fine mapping and DGE analyses revealed a nodulin 26-like intrinsic protein (NIP) gene, which encodes a likely boric acid channel. The gene co-expression network for putative B transporters also highlighted its central role in the efficiency of B uptake. An integration of whole-genome re-sequencing (WGS) with bulked segregant analysis (BSA) authenticated the emerging availability of QTL-seq for the QTL analyses in allotetraploid rapeseed. Transcriptomics-assisted QTL mapping and comparative genomics provided novel insights into the rapid identification of quantitative trait genes (QTGs) in plant species with complex genomes. PMID:26934080

  14. 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).

  15. 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.

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

    SciTech Connect

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

    1995-01-20

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

  17. 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

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

    PubMed

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

    2016-01-01

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

  19. 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.

  20. 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

  1. 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.

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

    PubMed

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

    2013-01-01

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

  3. 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.

  4. 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.

  5. Quantitative trait locus (QTL) isogenic recombinant analysis: a method for high-resolution mapping of QTL within a single population.

    PubMed

    Peleman, Johan D; Wye, Crispin; Zethof, Jan; Sørensen, Anker P; Verbakel, Henk; van Oeveren, Jan; Gerats, Tom; van der Voort, Jeroen Rouppe

    2005-11-01

    In the quest for fine mapping quantitative trait loci (QTL) at a subcentimorgan scale, several methods that involve the construction of inbred lines and the generation of large progenies of such inbred lines have been developed (Complex Trait Consortium 2003). Here we present an alternative method that significantly speeds up QTL fine mapping by using one segregating population. As a first step, a rough mapping analysis is performed on a small part of the population. Once the QTL have been mapped to a chromosomal interval by standard procedures, a large population of 1000 plants or more is analyzed with markers flanking the defined QTL to select QTL isogenic recombinants (QIRs). QIRs bear a recombination event in the QTL interval of interest, while other QTL have the same homozygous genotype. Only these QIRs are subsequently phenotyped to fine map the QTL. By focusing at an early stage on the informative individuals in the population only, the efforts in population genotyping and phenotyping are significantly reduced as compared to prior methods. The principles of this approach are demonstrated by fine mapping an erucic acid QTL of rapeseed at a subcentimorgan scale.

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

    SciTech Connect

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

    1993-01-01

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

  7. A physical map at 1p31 encompassing the acute insulin response locus and the leptin receptor

    SciTech Connect

    Thompson, D.B.; Sutherland, J.; Apel, W.; Ossowski, V.

    1997-01-15

    Recently, we reported genetic linkage in Pima Indians between the acute insulin response to an intravenous glucose challenge and the short tandem repeat marker D1S198, indicative of a genetic element in this region that controls the phenotypic variation in the first phase of insulin secretion. As a first step to isolating the gene responsible for the acute insulin response, we have constructed a yeast artificial chromosome (YAC) contig map that spans the DNA microsatellites D1S438 through D1S464. The contig comprises 34 YACs on which we have mapped 44 ends of the genomic DNA inserts from the 34 YACs, 13 short tandem repeats, eight expressed sequence tags, and six genes. In addition, we have used this contig to construct a physical map encompassing approximately 9 Mb of DNA in this region. 21 refs., 2 figs.

  8. 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.

  9. 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

  10. 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.

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

    PubMed Central

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

    2000-01-01

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


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

  12. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. Mapping of the Proteinase B Structural Gene PRB1, in SACCHAROMYCES CEREVISIAE and Identification of Nonsense Alleles within the Locus

    PubMed Central

    Zubenko, George S.; Mitchell, Aaron P.; Jones, Elizabeth W.

    1980-01-01

    We report the mapping of the structural gene for proteinase B, PRB1. It is located 1.1 cM proximal to CAN1 on the left arm of chromosome V of Saccharomyces cerevisiae. We have identified 34 amber and 12 ochre mutations among the 126 prb1 mutations in our collection. PMID:7009321

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

    PubMed

    Burrows, Courtney K; Kosova, Gülüm; Herman, Catherine; Patterson, Kristen; Hartmann, Katherine E; Velez Edwards, Digna R; Stephenson, Mary D; Lynch, Vincent J; Ober, Carole

    2016-07-01

    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

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

    PubMed

    Burrows, Courtney K; Kosova, Gülüm; Herman, Catherine; Patterson, Kristen; Hartmann, Katherine E; Velez Edwards, Digna R; Stephenson, Mary D; Lynch, Vincent J; Ober, Carole

    2016-07-01

    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.

  17. 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

  18. Quantitative trait locus (QTL) mapping using different testers and independent population samples in maize reveals low power of QTL detection and large bias in estimates of QTL effects.

    PubMed Central

    Melchinger, A E; Utz, H F; Schön, C C

    1998-01-01

    The efficiency of marker-assisted selection (MAS) depends on the power of quantitative trait locus (QTL) detection and unbiased estimation of QTL effects. Two independent samples N = 344 and 107 of F2 plants were genotyped for 89 RFLP markers. For each sample, testcross (TC) progenies of the corresponding F3 lines with two testers were evaluated in four environments. QTL for grain yield and other agronomically important traits were mapped in both samples. QTL effects were estimated from the same data as used for detection and mapping of QTL (calibration) and, based on QTL positions from calibration, from the second, independent sample (validation). For all traits and both testers we detected a total of 107 QTL with N = 344, and 39 QTL with N = 107, of which only 20 were in common. Consistency of QTL effects across testers was in agreement with corresponding genotypic correlations between the two TC series. Most QTL displayed no significant QTL x environment nor epistatic interactions. Estimates of the proportion of the phenotypic and genetic variance explained by QTL were considerably reduced when derived from the independent validation sample as opposed to estimates from the calibration sample. We conclude that, unless QTL effects are estimated from an independent sample, they can be inflated, resulting in an overly optimistic assessment of the efficiency of MAS. PMID:9584111

  19. Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval

    PubMed Central

    Aissani, Brahim; Zhang, Kui; Mensenkamp, Arjen R; Menko, Fred H; Wiener, Howard W

    2015-01-01

    Mutations in fumarate hydratase (FH) on chromosome 1q43 cause a rare cancer syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), but are rare in nonsyndromic and common uterine leiomyoma (UL) or fibroids. Studies suggested that variants in FH or in a linked gene may also predispose to UL. We re-sequenced 2.3 Mb of DNA spanning FH in 96 UL cases and controls from the multiethnic NIEHS-uterine fibroid study, and in 18 HLRCC-associated UL probands from European families then selected 221 informative SNPs for follow-up genotyping. We report promising susceptibility associations with UL peaking at rs78220092 (P=7.0×10−5) in the RGS7-FH interval in African Americans. In race-combined analyses and in meta-analyses (n=916), we identified promising associations with risk peaking upstream of a non-protein coding RNA (lncRNA) locus located in the RGS7-FH interval closer to RGS7, and associations with tumor size peaking in the distal phospholipase D family, member 5 (PLD5) gene at rs2654879 (P=1.7×10−4). We corroborated previously reported FH mutations in nine out of the 18 HLRCC-associated UL cases and identified two missense mutations in FH in only two nonsyndromic UL cases and one control. Our fine association mapping and integration of existing gene profiling data showing upregulated expression of the lncRNA and downregulation of PLD5 in fibroids, as compared to matched myometrium, suggest a potential role of this genomic region in UL pathogenesis. While the identified variations at 1q43 represent a potential risk locus for UL, future replication analyses are required to substantiate our observation. PMID:26113603

  20. 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

  1. 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

  2. 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

    2016-01-01

    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), 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. PMID:27600471

  3. Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval.

    PubMed

    Aissani, Brahim; Zhang, Kui; Mensenkamp, Arjen R; Menko, Fred H; Wiener, Howard W

    2015-08-01

    Mutations in fumarate hydratase (FH) on chromosome 1q43 cause a rare cancer syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), but are rare in nonsyndromic and common uterine leiomyoma (UL) or fibroids. Studies suggested that variants in FH or in a linked gene may also predispose to UL. We re-sequenced 2.3 Mb of DNA spanning FH in 96 UL cases and controls from the multiethnic NIEHS-uterine fibroid study, and in 18 HLRCC-associated UL probands from European families then selected 221 informative SNPs for follow-up genotyping. We report promising susceptibility associations with UL peaking at rs78220092 (P=7.0×10(-5)) in the RGS7-FH interval in African Americans. In race-combined analyses and in meta-analyses (n=916), we identified promising associations with risk peaking upstream of a non-protein coding RNA (lncRNA) locus located in the RGS7-FH interval closer to RGS7, and associations with tumor size peaking in the distal phospholipase D family, member 5 (PLD5) gene at rs2654879 (P=1.7×10(-4)). We corroborated previously reported FH mutations in nine out of the 18 HLRCC-associated UL cases and identified two missense mutations in FH in only two nonsyndromic UL cases and one control. Our fine association mapping and integration of existing gene profiling data showing upregulated expression of the lncRNA and downregulation of PLD5 in fibroids, as compared to matched myometrium, suggest a potential role of this genomic region in UL pathogenesis. While the identified variations at 1q43 represent a potential risk locus for UL, future replication analyses are required to substantiate our observation.

  4. 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

    Kolb, Aaron W; Lee, Kyubin; Larsen, Inna; Craven, Mark; Brandt, Curtis R

    2016-03-01

    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

  5. 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.

  6. 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

  7. 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

  8. Genetic analysis of heterosis for yield and yield components in rapeseed (Brassica napus L.) by quantitative trait locus mapping.

    PubMed

    Radoev, Mladen; Becker, Heiko C; Ecke, Wolfgang

    2008-07-01

    The main objective in this research was the genetic analysis of heterosis in rapeseed at the QTL level. A linkage map comprising 235 SSR and 144 AFLP markers covering 2045 cM was constructed in a doubled-haploid population from a cross between the cultivar "Express" and the resynthesized line "R53." In field experiments at four locations in Germany 250 doubled-haploid (DH) lines and their corresponding testcrosses with Express were evaluated for grain yield and three yield components. The heterosis ranged from 30% for grain yield to 0.7% for kernel weight. QTL were mapped using three different data sets, allowing the estimation of additive and dominance effects as well as digenic epistatic interactions. In total, 33 QTL were detected, of which 10 showed significant dominance effects. For grain yield, mainly complete dominance or overdominance was observed, whereas the other traits showed mainly partial dominance. A large number of epistatic interactions were detected. It was concluded that epistasis together with all levels of dominance from partial to overdominance is responsible for the expression of heterosis in rapeseed.

  9. Genetic analysis of heterosis for yield and yield components in rapeseed (Brassica napus L.) by quantitative trait locus mapping.

    PubMed

    Radoev, Mladen; Becker, Heiko C; Ecke, Wolfgang

    2008-07-01

    The main objective in this research was the genetic analysis of heterosis in rapeseed at the QTL level. A linkage map comprising 235 SSR and 144 AFLP markers covering 2045 cM was constructed in a doubled-haploid population from a cross between the cultivar "Express" and the resynthesized line "R53." In field experiments at four locations in Germany 250 doubled-haploid (DH) lines and their corresponding testcrosses with Express were evaluated for grain yield and three yield components. The heterosis ranged from 30% for grain yield to 0.7% for kernel weight. QTL were mapped using three different data sets, allowing the estimation of additive and dominance effects as well as digenic epistatic interactions. In total, 33 QTL were detected, of which 10 showed significant dominance effects. For grain yield, mainly complete dominance or overdominance was observed, whereas the other traits showed mainly partial dominance. A large number of epistatic interactions were detected. It was concluded that epistasis together with all levels of dominance from partial to overdominance is responsible for the expression of heterosis in rapeseed. PMID:18562665

  10. 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.

  11. Identification and mapping of a third blackleg resistance locus in Brassica napus derived from B. rapa subsp. sylvestris.

    PubMed

    Yu, Fengqun; Lydiate, Derek J; Rimmer, S Roger

    2008-01-01

    The spectrum of resistance to isolates of Leptosphaeria maculans and the map location of a new blackleg resistance gene found in the canola cultivar Brassica napus 'Surpass 400' are described. Two blackleg resistance genes, LepR1 and LepR2, from B. rapa subsp. sylvestris and introgressed in B. napus were identified previously. 'Surpass 400' also has blackleg resistance introgressed from B. rapa subsp. sylvestris. Using 31 diverse isolates of L. maculans, the disease reaction of 'Surpass 400' was compared with those of the resistant breeding lines AD9 (which contains LepR1), AD49 (which contains LepR2), and MC1-8 (which contains both LepR1 and LepR2). The disease reaction on 'Surpass 400' was different from those observed on AD9 and MC1-8, indicating that 'Surpass 400' carries neither LepR1 nor both LepR1 and LepR2 in combination. Disease reactions of 'Surpass 400' to most of the isolates tested were indistinguishable from those of AD49, which suggested 'Surpass 400' might contain LepR2 or a similar resistance gene. Classical genetic analysis of F1 and BC1 plants showed that a dominant allele conferred resistance to isolates of L. maculans in 'Surpass 400'. The resistance gene, which mapped to B. napus linkage group N10 in an interval of 2.9 cM flanked by microsatellite markers sR12281a and sN2428Rb and 11.7 cM below LepR2, was designated LepR3. A 9 cM region of the B. napus genome containing LepR3 was found to be syntenic with a segment of Arabidopsis chromosome 5.

  12. Mutants resistant to anti-microtubule herbicides map to a locus on the uni linkage group in Chlamydomonas reinhardtii

    SciTech Connect

    James, S.W.; Ranum, L.P.W.; Silflow, C.D.; Lefebvre, P.A.

    1988-01-01

    The authors have used genetic analysis to study the mode of action of two anti-microtubule herbicides, amiprophos-methyl (APM) and oryzaline (ORY). Over 200 resistant mutants were selected by growth on APM- or ORY-containing plates. The 21 independently isolated mutants examined in this study are 3- to 8-fold resistant to APM and are strongly cross-resistant to ORY and butamiphos, a close analog of APM. Two Mendelian genes, apm1 and apm2, are defined by linkage and complementation analysis. There are 20 alleles of apm1 and one temperature-sensitive lethal (33/sup 0/) allele of apm2. Mapping by two-factor crosses places apm1 6.5 cM centromere proximal to uni1 and within 4 cM of pf7 on the uni linkage group, a genetically circular linkage group comprising genes which affect flagellar assembly or function; apm2 maps near the centromere of linkage group VIII. Allele-specific synthetic lethality is observed in crosses between amp2 and alleles of apm1. Also, self crosses of apm2 are zygotic lethal, whereas crosses of nine apm1 alleles inter se result in normal germination and tetrad viability. The mutants are recessive to their wild-type alleles but doubly heterozygous diploids (apm1 +/+ apm2) made with apm2 and any of 15 apm1 alleles display partial intergenic noncomplementation, expressed as intermediate resistance. Diploids homozygous for mutant alleles of apm1 are 4-6-fold resistant to APM and ORY; diploids homozygous for apm2 are ts/sup -/ and 2-fold resistant to the herbicides. From the results described the authors suggest that the gene products of apm1 and apm2 may interact directly or function in the same structure or process.

  13. 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.

  14. 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

  15. Quantitative trait locus mapping of yield-related components and oligogenic control of the cap color of the button mushroom, Agaricus bisporus.

    PubMed

    Foulongne-Oriol, Marie; Rodier, Anne; Rousseau, Thierry; Savoie, Jean-Michel

    2012-04-01

    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 m(2), 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

  16. 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.

  17. Quantitative trait locus analysis, pathway analysis, and consomic mapping show genetic variants of Tnni3k, Fpgt, or H28 control susceptibility to viral myocarditis.

    PubMed

    Wiltshire, Sean A; Leiva-Torres, Gabriel André; Vidal, Silvia M

    2011-06-01

    Coxsackievirus B3 (CVB3) infection is the most common cause of viral myocarditis. The pathogenesis of viral myocarditis is strongly controlled by host genetic factors. Although certain indispensable components of immunity have been identified, the genes and pathways underlying natural variation between individuals remain unclear. Previously, we isolated the viral myocarditis susceptibility 1 (Vms1) locus on chromosome 3, which influences pathogenesis. We hypothesized that confirmation and further study of Vms1 controlling CVB3-mediated pathology, combined with pathway analysis and consomic mapping approaches, would elucidate both pathological and protective mechanisms accounting for natural variation in response to CVB3 infection. Vms1 was originally mapped to chromosome 3 using a segregating cross between susceptible A/J and resistant B10.A mice. To validate Vms1, C57BL/6J-Chr 3(A)/NaJ (a chromosome substitution strain that carries a diploid A/J chromosome 3) were used to replicate susceptibility compared with resistant C57BL/6J (B6). A second segregating F2 cross was generated between these, confirming both the localization and effects of Vms1. Microarray analysis of the four strains (A/J, B10.A, C57BL/6J, and C57BL/6J-Chr 3(A)/NaJ) illuminated a core program of response to CVB3 in all strains that is comprised mainly of IFN-stimulated genes. Microarray analysis also revealed strain-specific differential expression programs and genes that may be prognostic or diagnostic of susceptibility to CVB3 infection. A combination of analyses revealed very strong evidence for the existence and location of Vms1. Differentially expressed pathways were identified by microarray, and candidate gene analysis revealed Fpgt, H28, and Tnni3k as likely candidates for Vms1.

  18. 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

    2015-01-01

    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

  19. 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

  20. 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

    2015-01-01

    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.

  1. Mapping the end points of large deletions affecting the hprt locus in human peripheral blood cells and cell lines

    SciTech Connect

    Nelson, S.L.; Grosovsky, A.J.; Jones, I.M.; Burkhart-Schultz, K.; Fuscoe, J.C.

    1995-01-01

    We have examined the extent of of HPRT{sup {minus}} total gene deletions in three mutant collections: spontaneous and X-ray-induced deletions in TK6 human B lymphoblasts, and HPRT{sup {minus}} deletions arising in vivo in T cells. A set of 13 Xq26 STS markers surrounding hprt and spanning approximately 3.3 Mb was used. Each marker used was observed to be missing in at least one of the hprt deletion mutants analyzed. The largest deletion observed encompassed at least 3 Mb. Nine deletions extended outside of the mapped region in the centromeric direction (>1.7 Mb). In contrast, only two telomeric deletions extended to marker 342R (1.26 Mb), and both exhibited slowed or limited cell growth. These data suggest the existence of a gene, within the vicinity of 342R, which establishes the telomeric limit of recoverable deletions. Most (25/41) X-ray-induced total gene deletion mutants exhibited marker loss, but only 1/8 of the spontaneous deletions encompassed any Xq26 markers (P = 0.0187). Furthermore, nearly half (3/8) of the spontaneous 3{prime} total deletion breakpoints were within 14 kb of the hprt coding sequence. In contrast, 40/41 X-ray-induced HPRT{sup {minus}} total deletions extended beyond this point (P = 0.011). Although the overall representation of total gene deletions in the in vivo spectrum is low, 4/5 encompass Xq26 markers flanking hprt. This pattern differs significantly from spontaneous HPRT{sup {minus}} large deletions occurring in vitro (P = 0.032) but resembles the spectrum of X-ray-induced deletions. 24 refs., 6 figs., 1 tab.

  2. 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. PMID:27087578

  3. Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP

    PubMed Central

    Nexø, Bjørn A; Vogel, Ulla; Olsen, Anja; Nyegaard, Mette; Bukowy, Zuzanna; Rockenbauer, Eszter; Zhang, Xiuqing; Koca, Cemile; Mains, Mette; Hansen, Bettina; Hedemand, Anne; Kjeldgaard, Anette; Laska, Magdalena J; Raaschou-Nielsen, Ole; Cold, Søren; Overvad, Kim; Tjønneland, Anne; Bolund, Lars; Børglum, Anders D

    2008-01-01

    Background Previous results have suggested an association of the region of 19q13.3 with several forms of cancer. In the present study, we investigated 27 public markers within a previously identified 69 kb stretch of chromosome 19q for association with breast cancer by using linkage disequilibrium mapping. The study groups included 434 postmenopausal breast cancer cases and an identical number of individually matched controls. Methods and Results Studying one marker at a time, we found a region spanning the gene RAI (alias PPP1R13L or iASPP) and the 5' portion of XPD to be associated with this cancer. The region corresponds to a haplotype block, in which there seems to be very limited recombination in the Danish population. Studying combinations of markers, we found that two to four neighboring markers gave the most consistent and strongest result. The haplotypes with strongest association with cancers were located in the gene RAI and just 3' to the gene. Coinciding peaks were seen in the region of RAI in groups of women of different age. In a follow-up to these results we sequenced 10 cases and 10 controls in a 44 kb region spanning the peaks of association. This revealed 106 polymorphisms, many of which were not in the public databases. We tested an additional 44 of these for association with disease and found a new tandem repeat marker, called RAI-3'd1, located downstream of the transcribed region of RAI, which was more strongly associated with breast cancer than any other marker we have tested (RR = 2.44 (1.41–4.23, p = 0.0008, all cases; RR = 6.29 (1.49–26.6), p = 0.01, cases up to 55 years of age). Conclusion We expect the marker RAI-3'd1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer. PMID:18588689

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

    PubMed

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

    2016-01-01

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

  5. 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.

  6. 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.

  7. Fine mapping and targeted SNP survey using rice-wheat gene colinearity in the region of the Bo1 boron toxicity tolerance locus of bread wheat.

    PubMed

    Schnurbusch, Thorsten; Collins, Nicholas C; Eastwood, Russell F; Sutton, Tim; Jefferies, Steven P; Langridge, Peter

    2007-08-01

    Toxicity due to high levels of soil boron (B) represents a significant limitation to cereal production in some regions, and the Bo1 gene provides a major source of B toxicity tolerance in bread wheat (Triticum aestivum L.). A novel approach was used to develop primers to amplify and sequence gene fragments specifically from the Bo1 region of the hexaploid wheat genome. Single-nucleotide polymorphisms (SNPs) identified were then used to generate markers close to Bo1 on the distal end of chromosome 7BL. In the 16 gene fragments totaling 19.6 kb, SNPs were observed between the two cultivars Cranbrook and Halberd at a low frequency (one every 613 bp). Furthermore, SNPs were distributed unevenly, being limited to only two genes. In contrast, RFLP provided a much greater number of genetic markers, with every tested gene identifying polymorphism. Bo1 previously known only as a QTL was located as a discrete Mendelian locus. In total, 28 new RFLP, PCR and SSR markers were added to the existing map. The 1.8 cM Bo1 interval of wheat corresponds to a 227 kb section of rice chromosome 6L encoding 21 predicted proteins with no homology to any known B transporters. The co-dominant PCR marker AWW5L7 co-segregated with Bo1 and was highly predictive of B tolerance status within a set of 94 Australian bread wheat cultivars and breeding lines. The markers and rice colinearity described here represent tools that will assist B tolerance breeding and the positional cloning of Bo1. PMID:17571251

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

    PubMed 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

  9. 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

  10. 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. PMID:26826217

  11. 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

  12. 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.

  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. Mapping

    ERIC Educational Resources Information Center

    Kinney, Douglas M.; McIntosh, Willard L.

    1978-01-01

    Geologic mapping in the United States increased by about one-quarter in the past year. Examinations of mapping trends were in the following categories: (1) Mapping at scales of 1:100, 000; (2) Metric-scale base maps; (3) International mapping, and (4) Planetary mapping. (MA)

  15. A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum.

    PubMed

    Boukhris, Amir; Feki, Imed; Elleuch, Nizar; Miladi, Mohamed Imed; Boland-Augé, Anne; Truchetto, Jérémy; Mundwiller, Emeline; Jezequel, Nadia; Zelenika, Diana; Mhiri, Chokri; Brice, Alexis; Stevanin, Giovanni

    2010-10-01

    Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental impairment is a frequent subtype of complicated HSP, often inherited as an autosomal recessive (AR) trait. It is clear from molecular genetic analyses that there are several underlying causes of this syndrome, with at least six genetic loci identified to date. However, SPG11 and SPG15 are the two major genes for this entity. To map the responsible gene in a large AR-HSP-TCC family of Tunisian origin, we investigated a consanguineous family with a diagnosis of AR-HSP-TCC excluded for linkage to the SPG7, SPG11, SPG15, SPG18, SPG21, and SPG32 loci. A genome-wide scan was undertaken using 6,090 SNP markers covering all chromosomes. The phenotypic presentation in five patients was suggestive of a complex HSP that associated an early-onset spastic paraplegia with mild handicap, mental deterioration, congenital cataract, cerebellar signs, and TCC. The genome-wide search identified a single candidate region on chromosome 9, exceeding the LOD score threshold of +3. Fine mapping using additional markers narrowed the candidate region to a 45.1-Mb interval (15.4 cM). Mutations in three candidate genes were excluded. The mapping of a novel AR-HSP-TCC locus further demonstrates the extensive genetic heterogeneity of this condition. We propose that testing for this locus should be performed, after exclusion of mutations in SPG11 and SPG15 genes, in AR-HSP-TCC families, especially when cerebellar ataxia and cataract are present.

  16. Application of Genotyping-By-Sequencing for selection of locus-specific BAC clones to construct physical maps and identify candidate genes in Vitis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. Amh and Dmrta2 genes map to tilapia (Oreochromis spp.) linkage group 23 within quantitative trait locus regions for sex determination.

    PubMed

    Shirak, Andrey; Seroussi, Eyal; Cnaani, Avner; Howe, Aimee E; Domokhovsky, Raisa; Zilberman, Noam; Kocher, Thomas D; Hulata, Gideon; Ron, Micha

    2006-11-01

    Recent studies have revealed that the major genes of the mammalian sex determination pathway are also involved in sex determination of fish. Several studies have reported QTL in various species and strains of tilapia, regions contributing to sex determination have been identified on linkage groups 1, 3, and 23. Genes contributing to sex-specific mortality have been detected on linkage groups 2, 6, and 23. To test whether the same genes might control sex determination in mammals and fishes, we mapped 11 genes that are considered putative master key regulators of sex determination: Amh, Cyp19, Dax1, Dmrt2, Dmrta2, Fhl3l, Foxl2, Ixl, Lhx9, Sf1, and Sox8. We identified polymorphisms in noncoding regions of these genes and genotyped these sites for 90 individuals of an F2 mapping family. Mapping of Dax1 joined LG16 and LG21 into a single linkage group. The Amh and Dmrta2 genes were mapped to two distinct regions of LG23. The Amh gene was mapped 5 cM from UNH879 within a QTL region for sex determination and 2 cM from UNH216 within a QTL region for sex-specific mortality. Dmrta2 was mapped 4 cM from UNH848 within another QTL region for sex determination. Cyp19 was mapped to LG1 far from a previously reported QTL region for sex determination on this chromosome. Seven other candidate genes mapped to LG4, -11, -12, -14, and -17. PMID:16951079

  18. 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

  19. Physical and genetic mapping of the CMT4A locus and exclusion of PMP-2 as the defect in CMT4A

    SciTech Connect

    Othmane, K.B.; Loeb, D.; Roses, A.D.; Pericak-Vance, M.A.; Vance, J.M.

    1995-07-20

    We have previously localized one form of the autosomal recessive Charcot-Marie-Tooth disease type 4 (CMT4A) to a 5-cM region of chromosome 8q13-q21. We now report the formation of a 7-Bp YAC contig spanning the region. This contig was used to map nine additional microsatellites and six STSs to this region, and subsequent haplotype analysis has narrowed the CMT4A flanking interval to less than 1 cM. In addition, using SSCP and our physical map, we have demonstrated that the myelin protein PMP-2, mapped by FISH to this region, is not the defect in CMT4A. 27 refs., 3 figs., 1 tab.

  20. Genetic mapping of a locus for multiple ephiphyseal dysplasia (EDM2) to a region of chromosome 1 containing a type IX collagen gene

    SciTech Connect

    Briggs, M.D.; Choi, HiChang; Warman, M.L.; Loughlin, J.A.; Wordsworth, P.; Sykes, B.C.; Irven, C.M.M.; Smith, M.; Wynne-Davies, R.; Lipson, M.H.

    1994-10-01

    Multiple epiphyseal dysplasia (MED) is a dominantly inherited chondrodysplasia characterized by mild short stature and early-onset osteoarthrosis. Some forms of MED clinically resemble another chondrodysplasia phenotype, the mild form of pseudoachondroplasia (PSACH). On the basis of their clinical similarities as well as similar ultra-structural and biochemical features in cartilage from some patients, it has been proposed that MED and PSACH belong to a single bone-dysplasia family. Recently, both mild and severe PSACH as well as a form of MED have been linked to the same interval on chromosome 19, suggesting that they may be allelic disorders. Linkage studies with the chromosome 19 markers were carried out in a large family with MED and excluded the previously identified interval. Using this family, we have identified a MED locus on the short arm of chromosome 1, in a region containing the gene (COL9A2) that encodes the {alpha}2 chain of type IX collagen, a structural component of the cartilage extracellular matrix. 39 refs., 3 figs., 3 tabs.

  1. High-resolution tyramide-FISH mapping of markers tightly linked to the male-fertility restoration (Ms) locus of onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  2. 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

  3. Fine-Mapping of 18q21.1 Locus Identifies Single Nucleotide Polymorphisms Associated with Nonsyndromic Cleft Lip with or without Cleft Palate.

    PubMed

    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

  4. 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.

  5. 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)

  6. 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.

  7. Map-based cloning of a recessive genic male sterility locus in Brassica napus L. and development of its functional marker.

    PubMed

    Li, Ji; Hong, Dengfeng; He, Junping; Ma, Lei; Wan, Lili; Liu, Pingwu; Yang, Guangsheng

    2012-07-01

    We previously mapped one male-sterile gene (Bnms3) from an extensively used recessive genic male sterility line (9012AB) in Brassica napus to a 0.14-cM genomic region. In this study, two highly homologous BAC contigs possibly containing the candidate BnMs3 gene were identified using a map-based cloning strategy. A BnMs3-linked SCAR marker (DM1) capable of differentiating the subgenomes between B. rapa and the B. oleracea aided mapping of BnMs3 on the contig derived from the B. napus chromosome C9. One representative BAC clone was sequenced from each of the two contigs and resulted in a larger number of markers according to the sequence difference between the two clones. To isolate BnMs3, these markers were then analyzed in another two BC(1) populations with different genetic backgrounds. This assay allowed for a delimitation of the mutated functional region of BnMs3 to a 9.3-kb DNA fragment. Gene prediction suggested that one complete open reading frame (ORF, ORF2) and partial CDS fragments of ORF1 and ORF3 reside in this fragment. Sequence comparison and genetic transformation eventually indicated that ORF1 (designated as BnaC9.Tic40), an analogue of the Arabidopsis gene AT5G16620 which encodes a translocon of the inner envelope of chloroplasts 40 (Tic40), is the only candidate gene of BnMs3. Furthermore, two distinct mutation types in ORF1 both causing the male-sterile phenotype were individually revealed from 9012A and the temporary maintainer line T45. The molecular mechanism of this male sterility as well as the application of BnMs3-associated functional and cosegregated markers in true breeding programs was also discussed.

  8. 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

  9. Mapping of the DNA locus D4S10 and the linked Huntington's disease gene to 4p16----p15.

    PubMed

    Zabel, B U; Naylor, S L; Sakaguchi, A Y; Gusella, J F

    1986-01-01

    An anonymous DNA fragment (G8) detects two restriction fragment length polymorphic alleles (RFLPs) called D4S10 in HindIII-digested human genomic DNA. This segment had been assigned to chromosome 4 and shows close linkage to the Huntington's disease gene. With in situ hybridization, we mapped D4S10 to the terminal region of the short arm of chromosome 4, localizing the Huntington's disease gene to bands 4p16----p15. This information may prove useful for the development of strategies to clone the Huntington's disease gene.

  10. Design and analysis of genetic association studies to finely map a locus identified by linkage analysis: assessment of the extent to which an association can account for the linkage.

    PubMed

    Hanson, R L; Knowler, W C

    2008-01-01

    Association studies are often used to finely map quantitative trait loci identified by linkage analysis. Once a polymorphism associated with the trait has been identified, it may be useful to conduct linkage analyses which adjust for this polymorphism to determine the extent to which the association accounts for the linkage signal. However, methods for conducting statistical significance tests for an observed reduction in the linkage signal are not well developed. In the present study we develop methods for assessment of the statistical significance of an observed reduction in the variance due to the linked locus, with variance components or with Haseman-Elston linkage methods. Simulations indicate that these methods have appropriate levels of type I error and that, like other association statistics, their power depends on the magnitude of linkage disequilibrium between functional and marker alleles and on the extent of similarity between the frequency of the functional allele and the frequency of the associated marker allele. These methods can help determine which association results are likely due to strong linkage disequilibrium with functional alleles and, thus, can facilitate the selection of small chromosomal regions for more extensive study.

  11. Microsatellite-based fine mapping of the Van der Woude syndrome locus to an interval of 4.1 cM between D1S245 and D1S414

    SciTech Connect

    Sander, A.; Schmelzle, R.; Murray, J.C.; Scherpbier-Heddema, T.; Buetow, K.H.; Weissenbach, J.; Ludwig, K.; Zingg, M.

    1995-01-01

    Van der Woude syndrome (VWS) is an autosomal dominant craniofacial disorder characterized by lip pits, clefting of the primary or secondary palate, and hypodontia. The gene has been localized, by RFLP-based linkage studies, to region 1q32-41 between D1S65-REN and D1S65-TGFB2. In this study we report the linkage analysis of 15 VWS families, using 18 microsatellite markers. Multipoint linkage analysis places the gene, with significant odds of 2,344:1, in a 4.1-cM interval flanked by D1S245 and D1S414. Two-point linkage analysis demonstrates close linkage of VWS with D1S205 (lod score [Z] = 24.41 at {theta} = .00) and with D1S491 (Z = 21.23 at {theta} = .00). The results revise the previous assignment of the VWS locus and show in an integrated map of the region 1q32-42 that the VWS gene resides more distally than previously suggested. When information about heterozygosity of the closely linked marker D1S491 in the affected members of the VWS family with a microdeletion is taken into account, the VWS critical region can be further narrowed, to the 3.6-cM interval between D1S491 and D1S414. 38 refs., 3 figs., 2 tabs.

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

    PubMed

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

    2016-06-01

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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Comparative quantitative trait locus mapping of maize flowering-related traits in an F2:3 and recombinant inbred line population.

    PubMed

    Liu, Y H; Yi, Q; Hou, X B; Zhang, X G; Zhang, J J; Liu, H M; Hu, Y F; Huang, Y B

    2016-01-01

    Flowering-related traits in maize are affected by complex factors and are important for the improvement of cropping systems in the maize zone. Quantitative trait loci (QTLs) detected using different materials and methods usually vary. In the present study, 266 maize (Zea mays) F2:3 families and 301 recombinant inbred lines (RIL) derived from a cross between 08-641 (founding parent from southeast China) and Ye478 (founding parent from China) were evaluated for four flowering-related traits, including days to tasseling (DTT), days to pollen shedding (DPS), days to silking (DTS), and anthesis-silking interval. Sixty-six QTLs controlling the target traits were detected in the F2:3 and RIL populations via single environment analysis and joint analysis across all environments (JAAE). The QTLs explained 0.8-13.47% of the phenotypic variation, with 12 QTLs explaining more than 10%. The results of meta-QTL (MQTL) analysis indicated that 41 QTLs could be integrated into 14 MQTLs. One MQTL included 2.9 QTLs, ranging from two to ten QTLs for one to three traits. QTLs, including MQTL1-1 and MQTL9-1, were detected across the F2:3 and RIL populations via SAE and JAAE. Among the MQTLs, nine QTLs were integrated into MQTL9-1 and affected DTT, DPS, and DTS, with the favored allele being derived from 08-641. MQTL3-2 showed high phenotypic variation and was suitable for fine mapping to determine the genetic mechanisms of flowering. MQTL3-2 could be applied to improve inbred lines using marker-assisted selection. PMID:27420987

  18. Mapping of Mitochondrial Sorting Locus in Cucumber

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    PubMed Central

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

    1989-01-01

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

  20. Linkage map integration

    SciTech Connect

    Collins, A.; Teague, J.; Morton, N.E.; Keats, B.J.

    1996-08-15

    The algorithms that drive the map+ program for locus-oriented linkage mapping are presented. They depend on the enhanced location database program ldb+ to specify an initial comprehensive map that includes all loci in the summary lod file. Subsequently the map may be edited or order constrained and is automatically improved by estimating the location of each locus conditional on the remainder, beginning with the most discrepant loci. Operating characteristics permit rapid and accurate construction of linkage maps with several hundred loci. The map+ program also performs nondisjunction mapping with tests of nonstandard recombination. We have released map+ on Internet as a source program in the C language together with the location database that now includes the LODSOURCE database. 28 refs., 5 tabs.

  1. A new EcoRI polymorphism at the D21S13 locus.

    PubMed

    Pulst, S M; Korenberg, J R; Greenwald, J; Carbone, M

    1990-05-01

    The D21S13 locus has shown linkage to a gene for familial Alzheimer disease (FAD) on chromosome 21 (St. George-Hyslop et al. 1987). The limited informativeness of probes for this locus have hindered precise mapping of the FAD locus and analysis of nonallelic heterogeneity in FAD (Schellenberg et al. 1988; St. George-Hyslop et al. 1987). We describe a new EcoRI polymorphism at the D21S13 locus that may be useful for the further study of FAD families.

  2. A Cladistic Analysis of Phenotypic Associations with Haplotypes Inferred from Restriction Endonuclease Mapping or DNA Sequencing. V. Analysis of Case/Control Sampling Designs: Alzheimer's Disease and the Apoprotein E Locus

    PubMed Central

    Templeton, A. R.

    1995-01-01

    Present-day associations between haplotypes at a candidate locus and phenotypes exist when phenotypically important mutations occurred at some point during the evolution of the current array of genetic variation. A cladistic statistical design can be defined that focuses power by using the evolutionary history of the candidate DNA region. This paper shows how cladistic methodology is used for the analysis of case/control data, a common sampling design in genetic/disease association studies. A worked example is presented of the associations for sporadic early and late-onset forms of Alzheimer's disease with the 19q13.2 chromosomal region that includes the loci for apoproteins E, CI, and CII. This analysis confirms earlier reports of a strong association of the ApoE &4 allele with Alzheimer's disease but indicates that it is premature to condsider this association causal, particularly for early onset cases. Associations were also found with the &2 allele, as previously reported, and with the 1 allele at the ApoCI locus. However, this analysis indicates that it is inappropriate both statistically and medically to use single markers as risk predictors when haplotype data are available, even when the mutation leading to the marker is identified as having a strong phenotypic association. PMID:7635303

  3. Phenotypic and fine genetic characterization of the D locus controlling fruit acidity in peach

    PubMed Central

    2009-01-01

    Background Acidity is an essential component of the organoleptic quality of fleshy fruits. However, in these fruits, the physiological and molecular mechanisms that control fruit acidity remain unclear. In peach the D locus controls fruit acidity; low-acidity is determined by the dominant allele. Using a peach progeny of 208 F2 trees, the D locus was mapped to the proximal end of linkage group 5 and co-localized with major QTLs involved in the control of fruit pH, titratable acidity and organic acid concentration and small QTLs for sugar concentration. To investigate the molecular basis of fruit acidity in peach we initiated the map-based cloning of the D locus. Results In order to generate a high-resolution linkage map in the vicinity of the D locus, 1,024 AFLP primer combinations were screened using DNA of bulked acid and low-acid segregants. We also screened a segregating population of 1,718 individuals for chromosomal recombination events linked to the D locus and identified 308 individuals with recombination events close to D. Using these recombinant individuals we delimited the D locus to a genetic interval of 0.4 cM. We also constructed a peach BAC library of 52,000 clones with a mean insert size of 90 kb. The screening of the BAC library with markers tightly linked to D locus indicated that 1 cM corresponds to 250 kb at the vicinity of the D locus. Conclusion In the present work we presented the first high-resolution genetic map of D locus in peach. We also constructed a peach BAC library of approximately 15× genome equivalent. This fine genetic and physical characterization of the D locus is the first step towards the isolation of the gene(s) underlying fruit acidity in peach. PMID:19445673

  4. Genetic mapping of the Tsw locus for resistance to the Tospovirus Tomato spotted wilt virus in Capsicum spp. and its relationship to the Sw-5 gene for resistance to the same pathogen in tomato.

    PubMed

    Jahn, M; Paran, I; Hoffmann, K; Radwanski, E R; Livingstone, K D; Grube, R C; Aftergoot, E; Lapidot, M; Moyer, J

    2000-06-01

    The Tsw gene conferring dominant resistance to the Tospovirus Tomato spotted wilt virus (TSWV) in Capsicum spp. has been tagged with a random amplified polymorphic DNA marker and mapped to the distal portion of chromosome 10. No mapped homologues of Sw-5, a phenotypically similar dominant TSWV resistance gene in tomato, map to this region in C. annuum, although a number of Sw-5 homologues are found at corresponding positions in pepper and tomato. The relationship between Tsw and Sw-5 was also examined through genetic studies of TSWV. The capacity of TSWV-A to overcome the Tsw gene in pepper and the Sw-5 gene in tomato maps to different TSWV genome segments. Therefore, despite phenotypic and genetic similarities of resistance in tomato and pepper, we infer that distinct viral gene products control the outcome of infection in plants carrying Sw-5 and Tsw, and that these loci do not appear to share a recent common evolutionary ancestor.

  5. Characterization of the bvgR Locus of Bordetella pertussis

    PubMed Central

    Merkel, Tod J.; Barros, Cassia; Stibitz, Scott

    1998-01-01

    Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors is dependent upon the bvg locus (originally designated the vir locus), which encodes two proteins: BvgA, a 23-kDa cytoplasmic protein, and BvgS, a 135-kDa transmembrane protein. It is proposed that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regulator which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the bvg locus. Expression of this class, the bvg-repressed genes (vrgs [for vir-repressed genes]), is reduced under conditions in which expression of the aforementioned bvg-activated virulence factors is maximal; this repression is dependent upon the presence of an intact bvgAS locus. We have previously identified a locus required for regulation of all of the known bvg-repressed genes in B. pertussis. This locus, designated bvgR, maps to a location immediately downstream of bvgAS. We have undertaken deletion and complementation studies, as well as sequence analysis, in order to identify the bvgR open reading frame and identify the cis-acting sequences required for regulated expression of bvgR. Studies utilizing transcriptional fusions of bvgR to the gene encoding alkaline phosphatase have demonstrated that bvgR is activated at the level of transcription and that this activation is dependent upon an intact bvgAS locus. PMID:9537363

  6. 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

  7. 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

  8. 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. PMID:27171399

  9. 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

  10. 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.

  11. 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

  12. Locus of control and obesity.

    PubMed

    Neymotin, Florence; Nemzer, Louis R

    2014-01-01

    In the developed world, the hazards associated with obesity have largely outstripped the risk of starvation. Obesity remains a difficult public health issue to address, due in large part to the many disciplines involved. A full understanding requires knowledge in the fields of genetics, endocrinology, psychology, sociology, economics, and public policy - among others. In this short review, which serves as an introduction to the Frontiers in Endocrinology research topic, we address one cross-disciplinary relationship: the interaction between the hunger/satiation neural circuitry, an individual's perceived locus of control, and the risk for obesity. Mammals have evolved a complex system for modulating energy intake. Overlaid on this, in humans, there exists a wide variation in "perceived locus of control" - that is, the extent to which an individual believes to be in charge of the events that affect them. Whether one has primarily an internal or external locus of control itself affects, and is affected by, external and physiological factors and has been correlated with the risk for obesity. Thus, the path from hunger and satiation to an individual's actual behavior may often be moderated by psychological factors, included among which is locus of control. PMID:25339940

  13. 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.

  14. Prediction of multi-locus inbreeding coefficients and relation to linkage disequilibrium in random mating populations.

    PubMed

    Hill, William G; Weir, Bruce S

    2007-09-01

    An algorithm to predict the level of identity by descent simultaneously at multiple loci is presented, which can in principle be extended to any number of loci. The model assumes a random mating population, with random association of haplotypes. The relationship is shown between coefficients of multi-locus identity or non-identity by descent and moments of multi-locus linkage disequilibrium. Thus, these moments can be computed from the multilocus identity or, using algorithms derived previously to predict the disequilibria moments, vice-versa. The results can be applied to predict multi-locus identity in, for example, gene mapping.

  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. Dominant X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH/LIS): evidence for the occurrence of mutation in males and mapping of a potential locus in Xq22.

    PubMed Central

    des Portes, V; Pinard, J M; Smadja, D; Motte, J; Boespflüg-Tanguy, O; Moutard, M L; Desguerre, I; Billuart, P; Carrie, A; Bienvenu, T; Vinet, M C; Bachner, L; Beldjord, C; Dulac, O; Kahn, A; Ponsot, G; Chelly, J

    1997-01-01

    X linked subcortical laminar heterotopia and lissencephaly syndrome (XSCLH/ LIS) is an intriguing disorder of cortical development, which causes classical lissencephaly with severe mental retardation and epilepsy in hemizygous males, and subcortical laminar heterotopia (SCLH) associated with milder mental retardation and epilepsy in heterozygous females. Here we report an exclusion mapping study carried out in three unrelated previously described families in which males are affected with lissencephaly and females with SCLH, using 38 microsatellite markers evenly distributed on the X chromosome. Most of the X chromosome was excluded and potential intervals of assignment in Xq22.3-q23 or in Xq27 are reported. Although the number of informative meioses did not allow a decision between these two loci, it is worth noting that the former interval is compatible with the mapping of a breakpoint involved in a de novo X;autosomal balanced translocation 46,XX,t(X;2)(q22;p25) previously described in a female with classical lissencephaly. In addition, haplotype inheritance in two families showed a grandpaternal origin of the mutation and suggested in one family the presence of mosaicism in germline cells of normal transmitting males. Images PMID:9132485

  17. 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.

  18. Fixing the broken system of genetic locus symbols

    PubMed Central

    Lohmann, Katja; Lang, Anthony; Klein, Christine

    2012-01-01

    Originally, locus symbols (e.g., DYT1) were introduced to specify chromosomal regions that had been linked to a familial disorder with a yet unknown gene. Symbols were systematically assigned in a numerical series to designate mapped loci for a specific phenotype or group of phenotypes. Since the system of designating and using locus symbols was originally established, both our knowledge and our techniques of gene discovery have evolved substantially. The current system has problems that are sources of confusion, perpetuate misinformation, and misrepresent the system as a useful reference tool for a list of inherited disorders of a particular phenotypic class. These include erroneously assigned loci, duplicated loci, missing symbols, missing loci, unconfirmed loci in a consecutively numbered system, combining causative genes and risk factor genes in the same list, and discordance between phenotype and list assignment. In this article, we describe these problems and their impact, and propose solutions. The system could be significantly improved by creating distinct lists for clinical and research purposes, creating more informative locus symbols, distinguishing disease-causing mutations from risk factors, raising the threshold of evidence prior to assigning a locus symbol, paying strict attention to the predominant phenotype when assigning symbols lists, and having a formal system for reviewing and continually revising the list that includes input from both clinical and genetics experts. PMID:22454269

  19. Pitfalls in homozygosity mapping.

    PubMed

    Miano, M G; Jacobson, S G; Carothers, A; Hanson, I; Teague, P; Lovell, J; Cideciyan, A V; Haider, N; Stone, E M; Sheffield, V C; Wright, A F

    2000-11-01

    There is much interest in use of identity-by-descent (IBD) methods to map genes, both in Mendelian and in complex disorders. Homozygosity mapping provides a rapid means of mapping autosomal recessive genes in consanguineous families by identifying chromosomal regions that show homozygous IBD segments in pooled samples. In this report, we point out some potential pitfalls that arose during the course of homozygosity mapping of the enhanced S-cone syndrome gene, resulting from (1) unexpected allelic heterogeneity, so that the region containing the disease locus was missed as a result of pooling; (2) identification of a homozygous IBD region unrelated to the disease locus; and (3) the potential for inflation of LOD scores as a result of underestimation of the extent of inbreeding, which Broman and Weber suggest may be quite common.

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

    SciTech Connect

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

    1991-07-01

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

  1. 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.

  2. 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.

  3. Negative Complementation at the Notch Locus of DROSOPHILA MELANOGASTER

    PubMed Central

    Foster, Geoffrey G.

    1975-01-01

    Four Abruptex alleles (AxE1, AxE2, Ax9B2, and Ax16172) have been mapped within the Notch locus. Based on their visible phenotypes and their interactions with one another and with N mutations, the Ax alleles can be divided into two groups. Heterozygous combinations of members of the same group are intermediate in phenotype compared to the respective homozygotes, whereas heterozygotes of Ax alleles from different groups exhibit negative heterosis, being much less viable and more extremely mutant than either homozygote. It is suggested that the Notch locus is a multi-functional regulator ("integrator") gene, whose product possesses both "repressor" and "activator" functions for the processes it regulates. PMID:812768

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

    SciTech Connect

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

    1993-09-01

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

  5. A new HaeIII polymorphism at the D21S13 locus.

    PubMed

    Pulst, S M; Korenberg, J R; Ren, M; Greenwald, J

    1990-10-01

    DNA markers in the pericentromeric region of human chromosome 21 have shown linkage to a gene for Familial Alzheimer disease (FAD; St. George Hyslop et al. 1987). The limited informativeness of probes for the loci D21S13 and D21S16 have hindered precise mapping of the FAD locus and analysis of non-allelic heterogeneity in FAD (Schellenberg et al. 1988; St. George-Hyslop et al. 1987). We recently described a new EcoRII polymorphism at the D21S13 locus that was very informative in a large FAD pedigree (Pulst et al. 1990a,b). We now report another polymorphism for the D21S13 locus that further increases the informativeness of this locus.

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

    PubMed Central

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

    1990-01-01

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

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

    PubMed Central

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

    1996-01-01

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

  8. 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…

  9. Factors Determining Adolescent Locus of Control.

    ERIC Educational Resources Information Center

    Kopera-Frye, Karen F.; And Others

    Previous research has demonstrated an association between locus of control in adolescence and a successful transition to adulthood. Having an external locus of control has been implicated as an important factor in adolescent behaviors such as teenage pregnancy and delinquency, and has been found to be negatively related to school achievement. This…

  10. Deletion of tumor progression locus 2 attenuates alcohol induced hepatic inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: The pathogenesis of alcoholic liver disease (ALD) involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2), also known as Cancer Osaka Thyroid (COT) and MAP3K8, is a serine threonine kinase that functions as a critical regulator of inflammator...

  11. Fine Mapping and Introgressing a Fissure Resistance Locus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice (Oryza sativa L.) kernel fissuring is a major concern of both rice producers and millers. Fissures are small cracks in rice kernels that increase breakage among kernels when transported or milled, which decrease the value of processed rice. This study employed molecular gene tagging methods to ...

  12. Mapping polycomb response elements at the Drosophilla melanogaster giant locus.

    PubMed

    Abed, Jumana AlHaj; Cheng, Connie L; Crowell, Chase R; Madigan, Laura L; Onwuegbuchu, Erica; Desai, Siddhi; Benes, Judith; Jones, Richard S

    2013-12-01

    Polycomb-group (PcG) proteins are highly conserved epigenetic transcriptional regulators. They are capable of either maintaining the transcriptional silence of target genes through many cell cycles or enabling a dynamic regulation of gene expression in stem cells. In Drosophila melanogaster, recruitment of PcG proteins to targets requires the presence of at least one polycomb response element (PRE). Although the sequence requirements for PREs are not well-defined, the presence of Pho, a PRE-binding PcG protein, is a very good PRE indicator. In this study, we identify two PRE-containing regions at the PcG target gene, giant, one at the promoter, and another approximately 6 kb upstream. PRE-containing fragments, which coincide with localized presence of Pho in chromatin immunoprecipitations, were shown to maintain restricted expression of a lacZ reporter gene in embryos and to cause pairing-sensitive silencing of the mini-white gene in eyes. Our results also reinforce previous observations that although PRE maintenance and pairing-sensitive silencing activities are closely linked, the sequence requirements for these functions are not identical. PMID:24170735

  13. The Ace locus of Drosophila melanogaster: structural gene for acetylcholinesterase with an unusual 5' leader.

    PubMed Central

    Hall, L M; Spierer, P

    1986-01-01

    The Ace locus of Drosophila melanogaster has been mapped at the molecular level. cDNA clones from the locus have been isolated and their sequence determined, confirming that Ace forms the structural gene for acetylcholinesterase (AChE). The cDNAs have a 1950 nucleotide open reading frame from which the complete amino acid sequence of AChE has been deduced. The Drosophila enzyme is found to have extensive homology to the known sequence of Torpedo AChE. Ace cDNAs have an unusual structure with a long 5' leader and several short upstream open reading frames. Images Fig. 2. PMID:3024971

  14. Evidence that the Saethre-Chotzen syndrome locus lies between D7S664 and D7S507, by genetic analysis and detection of a microdeletion in a patient

    SciTech Connect

    Lewanda, A.F.; Jerald, H.; Taylor, E.; Jabs, E.W.; Green, E.D.; Weissenbach, J.; Summar, M.L.; Phillips, J.A. III; Cohen, M.; Feingold, M.

    1994-12-01

    The locus for Saethre-Chotzen syndrome, a common autosomal dominant disorder of craniosynostosis and digital anomalies, was previously mapped to chromosome 7p between D7S513 and D7S516. We used linkage and haplotype analyses to narrow the disease locus to an 8-cM region between D7S664 and D7S507. The tightest linkage was to locus D7S664 (Z = 7.16, {theta} = .00). chromosomes from a Saethre-Chotzen syndrome patient with t(2;7) (p23;p22) were used for in situ hybridization with YAC clones containing D7S664 and D7S507. The D7S664 locus was found to lie distal to the 7p22 breakpoint, and the D7S507 locus was deleted from the translocation chromosomes. These genetic and physical mapping data independently show that the disease locus resides in this interval.

  15. Developmental expression of the white locus of Drosophila melanogaster

    PubMed Central

    Fjose, A.; Polito, L. C.; Weber, U.; Gehring, W. J.

    1984-01-01

    We have isolated several cDNA clones of the white locus which are derived from embryonic and pupal transcripts of Drosophila melanogaster. The cDNA sequences map within ˜7.5 kb (coordinates −3.0 to +4.6) of the genomic DNA and correspond mainly to sequences within the distal region of the gene (coordinates −0.2 to −3.0). A major RNA species of 2.6 kb was detected on Northerns of poly(A)+ RNA isolated from all developmental stages. The total accumulation of this transcript peaks in the mature third instar larva to a level of 0.003% which is about ten times higher than that observed in embryos. The spatial distribution of white locus transcripts was determined by in situ hybridization to tissue sections. In embryos, hybridization signals are restricted to the cells of the developing Malpighian tubules and the signal strength corresponds with ˜50 transcripts per cell. Before the termination of the third instar stage, hybridization signals are also detected at a comparable level in the eye antennal disks. At the same stage, a third site of labeling is observed over a small cluster of cells which seems to be associated with the larval photoreceptor organs. Thus, white locus expression is largely restricted to tissues which are known to be involved in the biosynthesis of eye pigments and these different cell types act in a temporally autonomous manner with respect to the induction of the white gene during development. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5. PMID:16453550

  16. Molecular cloning of the white locus region of Drosophila melanogaster using a large transposable element

    PubMed Central

    Goldberg, M.L.; Paro, R.; Gehring, W.J.

    1982-01-01

    We report the molecular cloning of a chromosome segment including the white locus of Drosophila melanogaster. This region was isolated using a deficiency extending from the previously cloned heat-shock puff sequences at 87A7 to a large transposable element containing the loci white and roughest.FB-NOF, a 7.5 kb element with partial homology to a family of inverted repeat sequences (Potter et al., 1980), is found very near the deficiency breakpoint, and is followed by DNA originating from the white locus region. Sequences totalling ˜60 kb surrounding this initial entry point were obtained by the cloning of successively overlapping fragments from a wild-type strain. Several rearrangement breakpoints have been mapped relative to the cloned DNA; these define the limits of the white locus and further differentiate the “white proximal region”, thought to function in gene regulation, from the remainder of the locus. Insertion of the dispersed repetitive element copia into the white locus is observed in strains carrying the white-apricot allele. Analysis of several white-apricot revertants suggests that copia insertion is responsible for the apricot eye color phenotype. ImagesFig. 2.Fig. 4.Fig. 5.Fig. 6. PMID:16453411

  17. EM Algorithm for Mapping Quantitative Trait Loci in Multivalent Tetraploids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multivalent tetraploids that include many plant species, such as potato, sugarcane and rose, are of paramount importance to agricultural production and biological research. Quantitative trait locus (QTL) mapping in multivalent tetraploids is challenged by their unique cytogenetic properties, such ...

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

    SciTech Connect

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

    1994-09-01

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

  19. Genetic and molecular characterization of the I locus of Phaseolus vulgaris.

    PubMed

    Vallejos, C Eduardo; Astua-Monge, Gustavo; Jones, Valerie; Plyler, Tammy R; Sakiyama, Ney S; Mackenzie, Sally A

    2006-02-01

    The I locus of the common bean, Phaseolus vulgaris, controls the development of four different phenotypes in response to inoculation with Bean common mosaic virus, Bean common mosaic necrosis virus, several other related potyviruses, and one comovirus. We have generated a high-resolution linkage map around this locus and have aligned it with a physical map constructed with BAC clones. These clones were obtained from a library of the cultivar "Sprite," which carries the dominant allele at the I locus. We have identified a large cluster of TIR-NBS-LRR sequences associated within this locus, which extends over a distance >425 kb. Bean cultivars from the Andean or Mesoamerican gene pool that contain the dominant allele share the same haplotypes as revealed by gel blot hybridizations with a TIR probe. In contrast, beans with a recessive allele display simpler and variable haplotypes. A survey of wild accessions from Argentina to Mexico showed that this multigene family has expanded significantly during evolution and domestication. RNA gel blot analysis indicated that the TIR family of genes plays a role in the response to inoculations with BCMV or BCMNV. PMID:16322513

  20. Challenges and solutions for gene identification in the presence of familial locus heterogeneity

    PubMed Central

    Rehman, Atteeq U; Santos-Cortez, Regie Lyn P; Drummond, Meghan C; Shahzad, Mohsin; Lee, Kwanghyuk; Morell, Robert J; Ansar, Muhammad; Jan, Abid; Wang, Xin; Aziz, Abdul; Riazuddin, Saima; Smith, Joshua D; Wang, Gao T; Ahmed, Zubair M; Gul, Khitab; Shearer, A Eliot; Smith, Richard J H; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Hinnant, John; Khan, Shaheen N; Fisher, Rachel A; Ahmad, Wasim; Friderici, Karen H; Riazuddin, Sheikh; Friedman, Thomas B; Wilch, Ellen S; Leal, Suzanne M

    2015-01-01

    Next-generation sequencing (NGS) of exomes and genomes has accelerated the identification of genes involved in Mendelian phenotypes. However, many NGS studies fall short of identifying causal variants, with estimates for success rates as low as 25% for uncovering the pathological variant underlying disease etiology. An important reason for such failures is familial locus heterogeneity, where within a single pedigree causal variants in two or more genes underlie Mendelian trait etiology. As examples of intra- and inter-sibship familial locus heterogeneity, we present 10 consanguineous Pakistani families segregating hearing impairment due to homozygous variants in two different hearing impairment genes and a European-American pedigree in which hearing impairment is caused by four variants in three different genes. We have identified 41 additional pedigrees with syndromic and nonsyndromic hearing impairment for which a single previously reported hearing impairment gene has been identified but only segregates with the phenotype in a subset of affected pedigree members. We estimate that locus heterogeneity occurs in 15.3% (95% confidence interval: 11.9%, 19.9%) of the families in our collection. We demonstrate novel approaches to apply linkage analysis and homozygosity mapping (for autosomal recessive consanguineous pedigrees), which can be used to detect locus heterogeneity using either NGS or SNP array data. Results from linkage analysis and homozygosity mapping can also be used to group sibships or individuals most likely to be segregating the same causal variants and thereby increase the success rate of gene identification. PMID:25491636

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

    SciTech Connect

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

    1994-09-01

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

  2. Quantitative trait locus for reading disability on chromosome 6

    SciTech Connect

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

    1994-10-14

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

  3. Derivation of clones from the choroideremia locus by preparative field inversion gel electrophoresis.

    PubMed Central

    van de Pol, T J; Cremers, F P; Brohet, R M; Wieringa, B; Ropers, H H

    1990-01-01

    By making use of preparative field inversion gel electrophoresis, we have constructed a lambda ZAP library that is highly enriched for sequences from the choroideremia locus. In vivo excision of pBluescript SK(-) constructs from lambda ZAP obviates the subcloning of DNA inserts and allows for rapid processing of several hundred recombinants. From a 625 kb Sfil fragment we isolated 7 clones that were physically mapped using microdeletions associated with the disease. One of these clones is located within, or just telomeric to, the choroideremia gene and detects two restriction fragment length polymorphisms (RFLPs). Another clone detects a RFLP which maps centromeric to the disease locus. Together these probes should improve the reliability of linkage analysis in choroideremia families and should pave the way for the isolation of the choroideremia gene. Images PMID:1969148

  4. Transcriptome and allele specificity associated with a 3BL locus for Fusarium crown rot resistance in bread wheat.

    PubMed

    Ma, Jian; Stiller, Jiri; Zhao, Qiang; Feng, Qi; Cavanagh, Colin; Wang, Penghao; Gardiner, Donald; Choulet, Frédéric; Feuillet, Catherine; Zheng, You-Liang; Wei, Yuming; Yan, Guijun; Han, Bin; Manners, John M; Liu, Chunji

    2014-01-01

    Fusarium pathogens cause two major diseases in cereals, Fusarium crown rot (FCR) and head blight (FHB). A large-effect locus conferring resistance to FCR disease was previously located to chromosome arm 3BL (designated as Qcrs-3B) and several independent sets of near isogenic lines (NILs) have been developed for this locus. In this study, five sets of the NILs were used to examine transcriptional changes associated with the Qcrs-3B locus and to identify genes linked to the resistance locus as a step towards the isolation of the causative gene(s). Of the differentially expressed genes (DEGs) detected between the NILs, 12.7% was located on the single chromosome 3B. Of the expressed genes containing SNP (SNP-EGs) detected, 23.5% was mapped to this chromosome. Several of the DEGs and SNP-EGs are known to be involved in host-pathogen interactions, and a large number of the DEGs were among those detected for FHB in previous studies. Of the DEGs detected, 22 were mapped in the Qcrs-3B interval and they included eight which were detected in the resistant isolines only. The enrichment of DEG, and not necessarily those containing SNPs between the resistant and susceptible isolines, around the Qcrs-3B locus is suggestive of local regulation of this region by the resistance allele. Functions for 13 of these DEGs are known. Of the SNP-EGs, 28 were mapped in the Qcrs-3B interval and biological functions for 16 of them are known. These results provide insights into responses regulated by the 3BL locus and identify a tractable number of target genes for fine mapping and functional testing to identify the causative gene(s) at this QTL. PMID:25405461

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

    PubMed

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

    1999-06-01

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

  6. Locus of Control in Alcoholics Undergoing Treatment.

    ERIC Educational Resources Information Center

    Haley, Shirley C.

    Alcoholism is a complex behavior pattern. Social learning theory, which is concerned with the analysis of why individuals behave in certain ways and the effects of reinforcement patterns in their behaviors, offers an alternative to traditional treatments of alcoholics. Among alcoholics, drinking is a control issue. Locus of control is viewed as a…

  7. Aspirations, Attributions, and Locus of Control.

    ERIC Educational Resources Information Center

    Samuel, William; McNall, Sidne J.

    Self-evaluation is thought to play a major role in personality and motivation. Preliminary experience with success or failure, levels of aspiration, attributions for performance, and locus of control may all be interrelated factors in human motivation. After receiving success, failure, or no feedback on a concept formation task, subjects (N=90)…

  8. A suppressor locus for MODY3-diabetes

    PubMed Central

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

    2016-01-01

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

  9. Interactions between Proteins Encoded within the Human Cytomegalovirus UL133-UL138 Locus

    PubMed Central

    Petrucelli, Alex; Umashankar, Mahadevaiah; Zagallo, Patricia; Rak, Michael

    2012-01-01

    We previously described a novel genetic locus within the ULb′ region of the human cytomegalovirus (HCMV) genome that, while dispensable for replication in fibroblasts, suppresses replication in hematopoietic progenitors and augments replication in endothelial cells. This locus, referred to as the UL133-UL138 locus, encodes four proteins, pUL133, pUL135, pUL136, and pUL138. In this work, we have mapped the interactions among these proteins. An analysis of all pairwise interactions during transient expression revealed a robust interaction between pUL133 and pUL138. Potential interactions between pUL136 and both pUL133 and pUL138 were also revealed. In addition, each of the UL133-UL138 locus proteins self-associated, suggesting a potential to form higher-order homomeric complexes. As both pUL133 and pUL138 function in promoting viral latency in CD34+ hematopoietic progenitor cells (HPCs) infected in vitro, we further focused on this interaction. pUL133 and pUL138 are the predominant complex detected when all proteins are expressed together and require no other proteins in the locus for their association. During infection, the interaction between pUL133 and pUL138 or pUL136 can be detected. A recombinant virus that fails to express both pUL133 and pUL138 exhibited a latency phenotype similar to that of viruses that fail to express either pUL133 or pUL138, indicating that these proteins function cooperatively in latency and do not have independent functions that additively contribute to HCMV latency. These studies identify protein interactions among proteins encoded by the UL133-UL138 locus and demonstrate an important interaction impacting the outcome of HCMV infection. PMID:22674978

  10. Single locus affects embryonic segment polarity and multiple aspects of an adult evolutionary novelty

    PubMed Central

    2010-01-01

    Background The characterization of the molecular changes that underlie the origin and diversification of morphological novelties is a key challenge in evolutionary developmental biology. The evolution of such traits is thought to rely largely on co-option of a toolkit of conserved developmental genes that typically perform multiple functions. Mutations that affect both a universal developmental process and the formation of a novelty might shed light onto the genetics of traits not represented in model systems. Here we describe three pleiotropic mutations with large effects on a novel trait, butterfly eyespots, and on a conserved stage of embryogenesis, segment polarity. Results We show that three mutations affecting eyespot size and/or colour composition in Bicyclus anynana butterflies occurred in the same locus, and that two of them are embryonic recessive lethal. Using surgical manipulations and analysis of gene expression patterns in developing wings, we demonstrate that the effects on eyespot morphology are due to changes in the epidermal response component of eyespot induction. Our analysis of morphology and of gene expression in mutant embryos shows that they have a typical segment polarity phenotype, consistent with the mutant locus encoding a negative regulator of Wingless signalling. Conclusions This study characterizes the segregation and developmental effects of alleles at a single locus that controls the morphology of a lineage-specific trait (butterfly eyespots) and a conserved process (embryonic segment polarity and, specifically, the regulation of Wingless signalling). Because no gene with such function was found in the orthologous, highly syntenic genomic regions of two other lepidopterans, we hypothesize that our locus is a yet undescribed, possibly lineage-specific, negative regulator of the conserved Wnt/Wg pathway. Moreover, the fact that this locus interferes with multiple aspects of eyespot morphology and maps to a genomic region containing

  11. Expanded Genetic Map of Gibberella moniliformis (Fusarium verticillioides)†

    PubMed Central

    Jurgenson, James E.; Zeller, Kurt A.; Leslie, John F.

    2002-01-01

    Gibberella moniliformis (Fusarium verticillioides) is primarily a pathogen of maize, but it can also cause disease in other crop species. This pathogenicity, as well as the contamination of food- and feedstuffs with the fumonisin mycotoxins, results in economically significant losses to both farmers and food processors. The dissection of important biological characters in this fungus has been hampered by the lack of a uniformly dense genetic map. The existing restriction fragment length polymorphism-based map contains significant gaps, making it difficult to routinely locate biologically important genes, such as those involved in pathogenicity or mycotoxin production, with precision. We utilized amplified fragment length polymorphisms (AFLPs) to saturate the existing genetic map and added 486 AFLP markers to the ∼150 markers on the existing map. The resulting map has an average marker interval of 3.9 map units and averages ∼21 kb/map unit. The additional markers expanded the map from 1,452 to 2,188 map units distributed across 12 chromosomes. The maximum distance between adjacent markers is 29 map units. We identified AFLP markers less than 1 map unit from the mating type (MAT) locus and 2.5 map units from the spore killer (SK) locus; eight AFLP markers map within 8.5 units of the FUM1 (fumonisin biosynthetic) locus. The increased saturation of this map will facilitate further development of G. moniliformis as a model system for the genetic and population genetic studies of related, but less genetically tractable, plant pathogenic fungi. PMID:11916720

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

    SciTech Connect

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

    1989-12-01

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

  13. Development of a core set of single-locus SSR markers for allotetraploid rapeseed (Brassica napus L.).

    PubMed

    Li, Haitao; Younas, Muhammad; Wang, Xiaofeng; Li, Xuemin; Chen, Lin; Zhao, Bo; Chen, Xun; Xu, Jinsong; Hou, Fan; Hong, Baohua; Liu, Gang; Zhao, Hongyang; Wu, Xueli; Du, Hongzhi; Wu, Jiangsheng; Liu, Kede

    2013-04-01

    Brassica napus (AACC) is a recent allotetraploid species evolved through hybridization between two diploids, B. rapa (AA) and B. oleracea (CC). Due to extensive genome duplication and homoeology within and between the A and C genomes of B. napus, most SSR markers display multiple fragments or loci, which limit their application in genetics and breeding studies of this economically important crop. In this study, we collected 3,890 SSR markers from previous studies and also developed 5,968 SSR markers from genomic sequences of B. rapa, B. oleracea and B. napus. Of these, 2,701 markers that produced single amplicons were putative single-locus markers in the B. napus genome. Finally, a set of 230 high-quality single-locus SSR markers were established and assigned to the 19 linkage groups of B. napus using a segregating population with 154 DH individuals. A subset of 78 selected single-locus SSR markers was proved to be highly stable and could successfully discriminate each of the 45 inbred lines and hybrids. In addition, most of the 230 SSR markers showed the single-locus nature in at least one of the Brassica species of the U's triangle besides B. napus. These results indicated that this set of single-locus SSR markers has a wide range of coverage with excellent stability and would be useful for gene tagging, sequence scaffold assignment, comparative mapping, diversity analysis, variety identification and association mapping in Brassica species.

  14. Recombination Can Initiate and Terminate at a Large Number of Sites within the Rosy Locus of Drosophila Melanogaster

    PubMed Central

    Clark, S. H.; Hilliker, A. J.; Chovnick, A.

    1988-01-01

    This report presents the results of a recombination experiment designed to question the existence of special sites for the initiation or termination of a recombination heteroduplex within the region of the rosy locus. Intragenic recombination events were monitored between two physically separated rosy mutant alleles ry(301) and ry(2) utilizing DNA restriction site polymorphisms as genetic markers. Both ry(301) and ry(2) are known from previous studies to be associated with gene conversion frequencies an order of magnitude lower than single site mutations. The mutations are associated with large, well defined insertions located as internal sites within the locus in prior intragenic mapping studies. On the molecular map, they represent large insertions approximately 2.7 kb apart in the second and third exons, respectively, of the XDH coding region. The present study monitors intragenic recombination in a mutant heterozygous genotype in which DNA homology is disrupted by these large discontinuities, greater than the region of DNA homology and flanking both sides of the locus. If initiation/or termination requires separate sites at either end of the locus, then intragenic recombination within the rosy locus of the heterozygote should be eliminated. Contrary to expectation, significant recombination between these sites is seen. PMID:2834266

  15. Locus of Control and Psychological Distress among the Aged.

    ERIC Educational Resources Information Center

    Hale, W. Daniel; And Others

    1986-01-01

    Examined relationship between locus of control and self-reported psychopathology in 139 residents of retirement complex. Correlation coefficients computed for locus of control and each of nine symptom dimensions of the Brief Symptom Inventory indicated that locus of control was correlated with self-reported psychopatholgoy for older women but not…

  16. Cognitive Evaluation Theory, Locus of Control and Positive Verbal Feedback.

    ERIC Educational Resources Information Center

    Lonky, Edward; Reihman, Jacqueline

    This study tests the hypothesis that individual differences in locus of control orientation may mediate elementary school students' responses to positive verbal feedback. A total of 30 kindergarten through fourth grade subjects were assessed for locus of control orientation using the Bialer Children's Locus of Control Questionnaire. To establish a…

  17. Oakleaf: an S locus-linked mutation of Primula vulgaris that affects leaf and flower development.

    PubMed

    Cocker, Jonathan M; Webster, Margaret A; Li, Jinhong; Wright, Jonathan; Kaithakottil, Gemy; Swarbreck, David; Gilmartin, Philip M

    2015-10-01

    In Primula vulgaris outcrossing is promoted through reciprocal herkogamy with insect-mediated cross-pollination between pin and thrum form flowers. Development of heteromorphic flowers is coordinated by genes at the S locus. To underpin construction of a genetic map facilitating isolation of these S locus genes, we have characterised Oakleaf, a novel S locus-linked mutant phenotype. We combine phenotypic observation of flower and leaf development, with classical genetic analysis and next-generation sequencing to address the molecular basis of Oakleaf. Oakleaf is a dominant mutation that affects both leaf and flower development; plants produce distinctive lobed leaves, with occasional ectopic meristems on the veins. This phenotype is reminiscent of overexpression of Class I KNOX-homeodomain transcription factors. We describe the structure and expression of all eight P. vulgaris PvKNOX genes in both wild-type and Oakleaf plants, and present comparative transcriptome analysis of leaves and flowers from Oakleaf and wild-type plants. Oakleaf provides a new phenotypic marker for genetic analysis of the Primula S locus. We show that none of the Class I PvKNOX genes are strongly upregulated in Oakleaf leaves and flowers, and identify cohorts of 507 upregulated and 314 downregulated genes in the Oakleaf mutant.

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

    PubMed Central

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

    2000-01-01

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

  19. [Progresses of study on the DNA locus related to cytoplasmic male sterility and restorer gene for fertility in rapeseed].

    PubMed

    Ma, San-Mei; Wang, Yong-Fei

    2005-04-01

    CMS in rapeseed is of tremendous importance in its commercial application in hybrid seed production. This review focuses on the progresses of study on CMS in rapeseed from four aspects: (1) the mitochondrial DNA locus found to be associated with CMS, (2) the effects of restorer gene for fertility on the expression of the locus associated with CMS, (3) the mapping with molecular marker and (4) cloning of restorer genes of fertility of the CMS in rapeseed. The prospects of further studies on this subject are discussed.

  20. PAHdb 2003: what a locus-specific knowledgebase can do.

    PubMed

    Scriver, Charles R; Hurtubise, Mélanie; Konecki, David; Phommarinh, Manyphong; Prevost, Lynne; Erlandsen, Heidi; Stevens, Ray; Waters, Paula J; Ryan, Shannon; McDonald, David; Sarkissian, Christineh

    2003-04-01

    PAHdb, a legacy of and resource in genetics, is a relational locus-specific database (http://www.pahdb.mcgill.ca). It records and annotates both pathogenic alleles (n = 439, putative disease-causing) and benign alleles (n = 41, putative untranslated polymorphisms) at the human phenylalanine hydroxylase locus (symbol PAH). Human alleles named by nucleotide number (systematic names) and their trivial names receive unique identifier numbers. The annotated gDNA sequence for PAH is typical for mammalian genes. An annotated gDNA sequence is numbered so that cDNA and gDNA sites are interconvertable. A site map for PAHdb leads to a large array of secondary data (attributes): source of the allele (submitter, publication, or population); polymorphic haplotype background; and effect of the allele as predicted by molecular modeling on the phenylalanine hydroxylase enzyme (EC 1.14.16.1) or by in vitro expression analysis. The majority (63%) of the putative pathogenic PAH alleles are point mutations causing missense in translation of which few have a primary effect on PAH enzyme kinetics. Most apparently have a secondary effect on its function through misfolding, aggregation, and intracellular degradation of the protein. Some point mutations create new splice sites. A subset of primary PAH mutations that are tetrahydrobiopterin-responsive is highlighted on a Curators' Page. A clinical module describes the corresponding human clinical disorders (hyperphenylalaninemia [HPA] and phenylketonuria [PKU]), their inheritance, and their treatment. PAHdb contains data on the mouse gene (Pah) and on four orthologous mutant mouse models and their use (for example, in research on oral treatment of PKU with the enzyme phenylalanine ammonia lyase [EC 4.3.1.5]).

  1. Locus equations derived from compensatory articulation.

    PubMed

    Sussman, H M; Fruchter, D; Cable, A

    1995-05-01

    Locus equations are linear regressions of the onset of F2 transitions on their offsets. These functions vowel-normalize the F2 transitions such that they are able to characterize consonantal place categories. The purpose of this research was to determine if compensatory articulation due to bite blocks would alter the normally linear relationship between F2 transition onset and offset frequencies or alter the differential slopes and y intercepts of locus equations as a function of stop place. Six speakers, three male and three female, each produced /bVt/, /dVt/, and /gVt/ tokens for ten vowel contexts under normal and bite block conditions. Extremely linear and practically identical scatterplots were obtained in the two speaking conditions. No adaptation to the bite blocks was found when comparing locus equations derived from the initial versus the final bite block trial. Results are discussed in relation to the "orderly output constraint," which postulates a perceptual function for linearly related F2 transition end points within consonantal place categories.

  2. Bipolar disorder: Evidence for a major locus

    SciTech Connect

    Spence, M.A.; Flodman, P.L.; Sadovnick, A.D.; Ameli, H.

    1995-10-09

    Complex segregation analyses were conducted on families of bipolar I and bipolar II probands to delineate the mode of inheritance. The probands were ascertained from consecutive referrals to the Mood Disorder Service, University Hospital, University of British Columbia and diagnosed by DSM-III-R and Research Diagnostic Criteria. Data were available on over 1,500 first-degree relatives of the 186 Caucasian probands. The purpose of the analyses was to determine if, after correcting for age and birth cohort, there was evidence for a single major locus. Five models were fit to the data using the statistical package SAGE: (1) dominant, (2) recessive, (3) arbitrary mendelian inheritance, (4) environmental, and (5) no major effects. A single dominant, mendelian major locus was the best fitting of these models for the sample of bipolar I and II probands when only bipolar relatives were defined as affected (polygenic inheritance could not be tested). Adding recurrent major depression to the diagnosis {open_quotes}affected{close_quotes} for relatives reduced the evidence for a major locus effect. Our findings support the undertaking of linkage studies and are consistent with the analyses of the National Institutes of Mental Health (NIMH) Collaborative Study data by Rice et al. and Blangero and Elston. 39 refs., 4 tabs.

  3. Molecular analysis of radiation-induced albino (c)-locus mutations that cause death at preimplantation stages of development

    SciTech Connect

    Rinchik, E.M. ); Toenjes, R.R.; Paul, D. ); Potter, M.D. )

    1993-12-01

    Deletion mutations at the albino (c) locus have been useful for continuing the development of fine-structure physical and functional maps of the Fes-Hbb region of mouse chromosome 7. This report describes the molecular analysis of a number of radiation-induced c deletions that, when homozygous, cause death of the embryo during preimplantation stages. The distal extent of these deletions defines a locus, pid, (preimplantation development) genetically associated with this phenotype. The proximal breakpoints of eight of these deletions were mapped with respect to the Tyr (tyrosinase; albino) gene as well as to anonymous loci within the Fah-Tyr region that are defined by the Pmv-31 viral integration site and by chromosome-microdissection clones. Rearrangements corresponding to the proximal breakpoints of two of these deletions were detected by Southern blot analysis, and a size-altered restriction fragment carrying the breakpoint of one of them was cloned. A probe derived from this deletion fusion fragment defines a locus, D7Rn6, which maps within (or distal to) the pid region, and which discriminates among the distal extents of deletions eliciting the pid phenotype. Extension of physical maps from D7Rn6 should provide access both to the pid region and to loci mapping distal to pid that are defined by N-ethyl-N-nitrosourea-induced lethal mutations. 36 refs., 10 figs.

  4. A Gene Encoding a DUF247 Domain Protein Cosegregates with the S Self-Incompatibility Locus in Perennial Ryegrass.

    PubMed

    Manzanares, Chloé; Barth, Susanne; Thorogood, Daniel; Byrne, Stephen L; Yates, Steven; Czaban, Adrian; Asp, Torben; Yang, Bicheng; Studer, Bruno

    2016-04-01

    The grass family (Poaceae), the fourth largest family of flowering plants, encompasses the most economically important cereal, forage, and energy crops, and exhibits a unique gametophytic self-incompatibility (SI) mechanism that is controlled by at least two multiallelic and independent loci, S and Z. Despite intense research efforts over the last six decades, the genes underlying S and Z remain uncharacterized. Here, we report a fine-mapping approach to identify the male component of the S-locus in perennial ryegrass (Lolium perenne L.) and provide multiple evidence that a domain of unknown function 247 (DUF247) gene is involved in its determination. Using a total of 10,177 individuals from seven different mapping populations segregating for S, we narrowed the S-locus to a genomic region containing eight genes, the closest recombinant marker mapping at a distance of 0.016 cM. Of the eight genes cosegregating with the S-locus, a highly polymorphic gene encoding for a protein containing a DUF247 was fully predictive of known S-locus genotypes at the amino acid level in the seven mapping populations. Strikingly, this gene showed a frameshift mutation in self-compatible darnel (Lolium temulentum L.), whereas all of the self-incompatible species of the Festuca-Lolium complex were predicted to encode functional proteins. Our results represent a major step forward toward understanding the gametophytic SI system in one of the most important plant families and will enable the identification of additional components interacting with the S-locus.

  5. A monotonicity conjecture for real cubic maps

    SciTech Connect

    Dawson, S.P.; Galeeva, R.; Milnor, J.; Tresser, C.

    1993-12-01

    This will be an outline of work in progress. We study the conjecture that the topological entropy of a real cubic map depends ``monotonely`` on its parameters, in the sense that each locus of constant entropy in parameter space is a connected set. This material will be presented in more detail in a later paper.

  6. Single locus sex determination and female heterogamety in the basket willow (Salix viminalis L.).

    PubMed

    Pucholt, P; Rönnberg-Wästljung, A-C; Berlin, S

    2015-06-01

    Most eukaryotes reproduce sexually and a wealth of different sex determination mechanisms have evolved in this lineage. Dioecy or separate sexes are rare among flowering plants but have repeatedly evolved from hermaphroditic ancestors possibly involving male or female sterility mutations. Willows (Salix spp.) and poplars (Populus spp.) are predominantly dioecious and are members of the Salicaceae family. All studied poplars have sex determination loci on chromosome XIX, however, the position differs among species and both male and female heterogametic system exists. In contrast to the situation in poplars, knowledge of sex determination mechanisms in willows is sparse. In the present study, we have for the first time positioned the sex determination locus on chromosome XV in S. viminalis using quantitative trait locus mapping. All female offspring carried a maternally inherited haplotype, suggesting a system of female heterogamety or ZW. We used a comparative mapping approach and compared the positions of the markers between the S. viminalis linkage map and the physical maps of S. purpurea, S. suchowensis and P. trichocarpa. As we found no evidence for chromosomal rearrangements between chromosome XV and XIX between S. viminalis and P. trichocarpa, it shows that the sex determination loci in the willow and the poplar most likely do not share a common origin and has thus evolved separately. This demonstrates that sex determination mechanisms in the Salicaceae family have a high turnover rate and as such it is excellent for studies of evolutionary processes involved in sex chromosome turnover.

  7. Single locus sex determination and female heterogamety in the basket willow (Salix viminalis L.)

    PubMed Central

    Pucholt, P; Rönnberg-Wästljung, A-C; Berlin, S

    2015-01-01

    Most eukaryotes reproduce sexually and a wealth of different sex determination mechanisms have evolved in this lineage. Dioecy or separate sexes are rare among flowering plants but have repeatedly evolved from hermaphroditic ancestors possibly involving male or female sterility mutations. Willows (Salix spp.) and poplars (Populus spp.) are predominantly dioecious and are members of the Salicaceae family. All studied poplars have sex determination loci on chromosome XIX, however, the position differs among species and both male and female heterogametic system exists. In contrast to the situation in poplars, knowledge of sex determination mechanisms in willows is sparse. In the present study, we have for the first time positioned the sex determination locus on chromosome XV in S. viminalis using quantitative trait locus mapping. All female offspring carried a maternally inherited haplotype, suggesting a system of female heterogamety or ZW. We used a comparative mapping approach and compared the positions of the markers between the S. viminalis linkage map and the physical maps of S. purpurea, S. suchowensis and P. trichocarpa. As we found no evidence for chromosomal rearrangements between chromosome XV and XIX between S. viminalis and P. trichocarpa, it shows that the sex determination loci in the willow and the poplar most likely do not share a common origin and has thus evolved separately. This demonstrates that sex determination mechanisms in the Salicaceae family have a high turnover rate and as such it is excellent for studies of evolutionary processes involved in sex chromosome turnover. PMID:25649501

  8. Evolution of sex-specific wing shape at the widerwing locus in four species of Nasonia.

    PubMed

    Loehlin, D W; Enders, L S; Werren, J H

    2010-03-01

    How do morphological differences between species evolve at the genetic level? This study investigates the genetic basis of recent divergence in male wing size between species of the model parasitoid wasp Nasonia. The forewings of flightless Nasonia vitripennis males are 2.3 times smaller than males of their flighted sister species N. giraulti. We describe a major genetic contributor to this difference: the sex-specific widerwing (wdw) locus, which we have backcrossed from N. giraulti into N. vitripennis and mapped to an 0.9 megabase region of chromosome 1. This introgression of wdw from large-winged N. giraulti into small-winged N. vitripennis increases male but not female forewing width by 30% through wing region-specific size changes. Indirect evidence suggests that cell number changes across the wing explain the majority of the wdw wing-size difference, whereas changes in cell size are important in the center of the wing. Introgressing the same locus from the other species in the genus, N. longicornis and N. oneida, into N. vitripennis produces intermediate and large male wing sizes. To our knowledge, this is the first study to introgress a morphological quantitative trait locus (QTL) from multiple species into a common genetic background. Epistatic interactions between wdw and other QTL are also identified by introgressing wdw from N. vitripennis into N. giraulti. The main findings are (1) the changes at wdw have sex- and region-specific effects and could, therefore, be regulatory, (2) the wdw locus seems to be a co-regulator of cell size and cell number, and (3) the wdw locus has evolved different wing width effects in three species.

  9. Molecular characterization of the tia invasion locus from enterotoxigenic Escherichia coli.

    PubMed Central

    Fleckenstein, J M; Kopecko, D J; Warren, R L; Elsinghorst, E A

    1996-01-01

    Enterotoxigenic Escherichia coli (ETEC) shares with other diarrheal pathogens the capacity to invade epithelial cell lines originating from the human ileum or colon, although the role of invasion in ETEC pathogenesis remains undefined. Two distinct loci (tia and tib) that direct noninvasive E. coli to adhere to and invade intestinal epithelial cell lines have previously been isolated from cosmid libraries of the classical ETEC strain H10407. Here, we report the molecular characterization of the tia locus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of cellular fractions of E. coli DH5alpha carrying the tia-positive cosmids and recombinant plasmid subclones revealed that this locus directs the production of a 25-kDa protein (the Tia protein) that is localized to the outer membrane. The tia locus was subcloned to a maximum of 2 kb and mutagenized with bacteriophage Mud. Synthesis of this protein was directly correlated with the ability of subclones and Mud transposon mutants to adhere to and invade epithelial cells. Sequencing of the tia locus identified a 756-bp open reading frame. All transposon insertions resulting in an invasion-negative phenotype mapped to this open reading frame. The open reading frame was amplified and directionally cloned behind the lac promoter of pHG165. This construct directed DHalpha to express a 25-kDa protein and to adhere to and invade epithelial cells. The role of the tia gene in directing epithelial adherence and invasion was further assessed by the construction of chromosomal tia deletion derivatives of the parent ETEC strain, H10407. These tia deletion strains were noninvasive and lacked the ability to adhere to human ileocecal cells. The tia gene shares limited homology with the Yersinia ail locus and significant homology with the hra1 agglutinin gene cloned from a porcine ETEC strain. Additionally, tia probes hybridized to geographically diverse ETEC strains, as well as some enteropathogenic E. coli

  10. Evolution of sex-specific wing shape at the widerwing locus in four species of Nasonia

    PubMed Central

    Loehlin, David W.; Enders, Laramy S.; Werren, John H.

    2009-01-01

    How do morphological differences between species evolve at the genetic level? This study investigates the genetic basis of recent divergence in male wing size between species of the model parasitoid wasp Nasonia. The forewings of flightless N. vitripennis males are 2.3 times smaller than males of their flighted sister species N. giraulti. We describe a major genetic contributor to this difference: the sex-specific widerwing (wdw) locus, which we have backcrossed from N. giraulti into N. vitripennis and mapped to an 0.9 megabase region of chromosome 1. This introgression of wdw from large-winged N. giraulti into small-winged N. vitripennis increases male but not female forewing width by 30% through wing region-specific size changes. Indirect evidence suggests that cell number changes across the wing explain the majority of the wdw wing size difference while changes in cell size are important in the center of the wing. Introgressing the same locus from the other species in the genus, N. longicornis and N. oneida, into N. vitripennis produces intermediate and large male wing sizes. To our knowledge, this is the first study to introgress a morphological quantitative trait locus (QTL) from multiple species into a common genetic background. Epistatic interactions between wdw and other QTL are also identified by introgressing wdw from N. vitripennis into N. giraulti. The main findings are 1) the changes at wdw have sex- and region-specific effects and could therefore be regulatory, 2) the wdw locus appears to be a co-regulator of cell size and cell number, and 3) the wdw locus has evolved different wing width effects in three species. PMID:20087390

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

    PubMed Central

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

    1994-01-01

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

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

    SciTech Connect

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

    1994-07-05

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

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

    PubMed

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

    1996-01-01

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

  14. Familial cutaneous malignant melanoma: autosomal dominant trait possibly linked to the Rh locus.

    PubMed Central

    Greene, M H; Goldin, L R; Clark, W H; Lovrien, E; Kraemer, K H; Tucker, M A; Elder, D E; Fraser, M C; Rowe, S

    1983-01-01

    Segregation and linkage analyses were undertaken in families with multiple cases of cutaneous malignant melanoma (CMM) and a recently-described melanoma precursor, the dysplastic nevus syndrome (DNS). Clinical and laboratory data, including 23 genetic markers, were collected on 401 members of 14 high-risk kindreds. Pedigree analysis was compatible with an autosomal dominant mode of inheritance for the familial CMM trait. Although a similar model probably applies to the DNS trait as well, segregation analysis could not confirm the presence of a major locus. However, linkage analysis suggested that an autosomal dominant model was appropriate for the DNS, and that a DNS/CMM susceptibility gene may be located on the short arm of chromosome 1, within 30 map units of the Rh locus [maximum logarithm of odds (lod) score = 2.00]. Images PMID:6577466

  15. Variation at the fragile X locus does not influence susceptibility to bipolar disorder

    SciTech Connect

    Craddock, N.; Daniels, J.; McGuffin, P.

    1994-06-15

    Over the last 20 years several pedigrees have been reported which are suggestive of linkage between susceptibility to bipolar disorder and markers on chromosome Xq28. Other workers have failed to replicate these reports and the methodology of the positive reports has been criticized. Recently there have been several reports of an association between fragile X (FRA(X)) and affective disorder within families and in unrelated individuals compared with controls. Such reports could be consistent with the Xq28 marker reports because FRA(X) maps to Xq27.3. We report a study at the FRA(X) CGG repeat locus in 79 unrelated Caucasian bipolar probands without fragile X syndrome and 77 unrelated controls. We found no evidence that variation at this locus confers susceptibility to bipolar disorder. 28 refs., 1 fig.

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

    SciTech Connect

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

    1994-09-01

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

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

    PubMed

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

    2010-12-01

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

  18. Genome-Wide Association Study Identifies a Novel Canine Glaucoma Locus

    PubMed Central

    Ahonen, Saija J.; Pietilä, Elina; Mellersh, Cathryn S.; Tiira, Katriina; Hansen, Liz; Johnson, Gary S.; Lohi, Hannes

    2013-01-01

    Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG), primary open-angle (POAG) and primary congenital glaucoma (PCG). Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT) in which it is a late-onset (>7 years) disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively) in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63×10−10, OR = 32 for homozygosity). Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease. PMID:23951034

  19. Regulatory organization of the staphylococcal sae locus.

    PubMed

    Adhikari, Rajan P; Novick, Richard P

    2008-03-01

    This paper describes an investigation of the complex internal regulatory circuitry of the staphylococcal sae locus and the impact of modifying this circuitry on the expression of external genes in the sae regulon. The sae locus contains four genes, the saeR and S two-component signalling module (TCS), and saeP and Q, two upstream genes of hitherto unknown function. It is expressed from two promoters, P(A)sae, which transcribes only the TCS, and P(C)sae, which transcribes the entire locus. A bursa aurealis (bursa) transposon insertion in saeP in a derivative of Staphylococcus aureus NCTC 8325 has a profound effect on sae function. It modifies the activity of the TCS, changing the expression of many genes in the sae regulon, even though transcription of the TCS (from P(A)sae) is not interrupted. Moreover, these effects are not due to disruption of saeP since an in-frame deletion in saeP has essentially no phenotype. The phenotype of S. aureus strain Newman is remarkably similar to that of the saeP : : bursa and this similarity is explained by an amino acid substitution in the Newman saeS gene that is predicted to modify profoundly the signalling function of the protein. This concurrence suggests that the saeP : : bursa insertion affects the signalling function of saeS, a suggestion that is supported by the ability of an saeQR clone, but not an saeR clone, to complement the effects of the saeP : : bursa insertion.

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

    PubMed Central

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

    1991-01-01

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

  1. A major locus expressed in the male gametophyte with incomplete penetrance is responsible for in situ gynogenesis in maize.

    PubMed

    Barret, P; Brinkmann, M; Beckert, M

    2008-08-01

    In flowering plants, double fertilization occurs when the egg cell and the central cell are each fertilized by one sperm cell. In maize, some lines produce pollen capable of inducing in situ gynogenesis thereby leading to maternal haploids that originate exclusively from the female plant. In this paper, we present a genetic analysis of in situ gynogenesis in maize. Using a cross between non-inducing and inducing lines, we identified a major locus on maize chromosome 1 controlling in situ gynogenesis (ggi1, for gynogenesis inducer 1). Fine mapping of this locus was performed, and BAC physical contigs spanning the locus were identified using the rice genome as anchor. Genetic component analysis showed that (a) a segregation distortion against the inducer parent was present at this locus, (b) segregation resulted only from male deficiency and (c) there was a correlation between the rate of segregation distortion and the level of gynogenetic induction. In addition, our results showed that the genotype of the pollen determined its capacity to induce the formation of a haploid female embryo, indicating gametophytic expression of the character with incomplete penetrance. We propose the occurrence of a gametophytic-specific process which leads to segregation distortion at the ggi1 locus associated with gynogenetic induction with incomplete penetrance.

  2. Locus of control and psychological distress among the aged.

    PubMed

    Hale, W D; Hedgepeth, B E; Taylor, E B

    A relationship between locus of control and adjustment has been found in many studies of young adults, with externals generally reporting higher levels of psychological distress. However, studies of locus of control and adjustment in the aged have produced conflicting results. This investigation examined the relationship between locus of control and self-reported psychopathology in a sample of 139 residents of a retirement complex. Correlation coefficients were computed for locus of control and each of the nine symptom dimensions of the Brief Symptom Inventory. These analyses were carried out separately for males and for females to determine if locus of control orientation was associated with adjustment for both males and females. Results indicate that locus of control is correlated with self-reported psychopathology for older women but not for older men. These results and those of related investigations are discussed within the context of Rotter's social learning theory.

  3. Genetic characterization and regulation of the nadB locus of Salmonella typhimurium.

    PubMed Central

    Cookson, B T; Olivera, B M; Roth, J R

    1987-01-01

    The nadB locus encodes the first enzyme of NAD synthesis. It has been reported that this gene and nadA are regulated by a positive regulatory protein encoded in the nadB region. In pursuing this regulatory mechanism, we constructed a fine-structure genetic map of the nadB gene. The region appears to include a single complementation group; no evidence for a positive regulatory element was found. Several mutations causing resistance to the analog 6-aminonicotinamide mapped within the structural gene and probably cause resistance to feedback inhibition. Regulatory mutations for nadB were isolated. These mutants mapped far from nadB near the pnuA gene, which encodes a function required for nicotinamide mononucleotide transport. The regulatory mutations appear to affect a distinct function encoded in the same operon as pnuA. PMID:3305482

  4. The human PECAM1 gene maps to 17q23

    SciTech Connect

    Gumina, R.J.; Rao, P.N.; Tuinen, P. van

    1996-06-01

    We have determined the chromosomal and regional location of the gene encoding PECAM-1 (termed PECAM1 by GBI) nomenclature using a polymerase chain reaction (PCR)-based analysis of somatic cell hybrids. Analysis of a somatic cell hybrid chromosome panel established that the PECAM1 gene is on chromosome 17. Interestingly, several adhesion molecules expressed on platelets and endothelium also localize to chromosome 17: the GP1BA locus (glycoprotein (GP) Ib{alpha}) has been provisionally mapped to the region 17p12-pter, the ITGA2b (GPIIb) and the ITGB3 (GPI-IIa) loci have been confirmed to the region 17q21.32; and the ICAM2 locus has been provisionally mapped to the region 17q23-q25. To determine if the PECAM1 locus colocalizes with any of the loci for these adhesion molecules, PCR-based analysis of a regional mapping panel for human chromosome 17 was conducted. We found that the PECAM1 locus is on the long arm of chromosome 17, i the region q23-qter. To confirm this observation and obtain a more precise localization of the PECAM1 locus, fluorescence in situ hybridization was conducted. Together our data allowed assignment of the PECAM1 locus to the region 17q23. 18 refs., 2 figs.

  5. The cell: locus or object of inquiry?

    PubMed

    Bechtel, William

    2010-09-01

    Research in many fields of biology has been extremely successful in decomposing biological mechanisms to discover their parts and operations. It often remains a significant challenge for scientists to recompose these mechanisms to understand how they function as wholes and interact with the environments around them. This is true of the eukaryotic cell. Although initially identified in nineteenth-century cell theory as the fundamental unit of organisms, researchers soon learned how to decompose it into its organelles and chemical constituents and have been highly successful in understanding how these carry out many operations important to life. The emphasis on decomposition is particularly evident in modern cell biology, which for the most part has viewed the cell as merely a locus of the mechanisms responsible for vital phenomena. The cell, however, is also an integrated system and for some explanatory purposes it is essential to recompose it and understand it as an organized whole. I illustrate both the virtues of decomposition (treating the cell as a locus) and recomposition (treating the cell as an object) with recent work on circadian rhythms. Circadian researchers have both identified critical intracellular operations that maintain endogenous oscillations and have also addressed the integration of cells into multicellular systems in which cells constitute units.

  6. Interallelic complementation at the mouse Mitf locus.

    PubMed Central

    Steingrímsson, Eiríkur; Arnheiter, Heinz; Hallsson, Jón Hallsteinn; Lamoreux, M Lynn; Copeland, Neal G; Jenkins, Nancy A

    2003-01-01

    Mutations at the mouse microphthalmia locus (Mitf) affect the development of different cell types, including melanocytes, retinal pigment epithelial cells of the eye, and osteoclasts. The MITF protein is a member of the MYC supergene family of basic-helix-loop-helix-leucine-zipper (bHLHZip) transcription factors and is known to regulate the expression of cell-specific target genes by binding DNA as homodimer or as heterodimer with related proteins. The many mutations isolated at the locus have different effects on the phenotype and can be arranged in an allelic series in which the phenotypes range from near normal to white microphthalmic animals with osteopetrosis. Previous investigations have shown that certain combinations of Mitf alleles complement each other, resulting in a phenotype more normal than that of each homozygote alone. Here we analyze this interallelic complementation in detail and show that it is limited to one particular allele, Mitf(Mi-white) (Mitf(Mi-wh)), a mutation affecting the DNA-binding domain. Both loss- and gain-of-function mutations are complemented, as are other Mitf mutations affecting the DNA-binding domain. Furthermore, this behavior is not restricted to particular cell types: Both eye development and coat color phenotypes are complemented. Our analysis suggests that Mitf(Mi-wh)-associated interallelic complementation is due to the unique biochemical nature of this mutation. PMID:12586714

  7. A novel Drosophila Minute locus ribosomal protein S13

    SciTech Connect

    Saeboe-Larssen, S.; Lambertsson, A.

    1996-06-01

    Minutes comprise >50 phenotypically similar Drosophila mutations believed to affect ribosomal protein genes. Common traits of the Minute phenotype are short and thin bristles, slow development, and recessive lethality. To further investigate the proposed Minute to ribosomal protein correspondence, loss-of-function Minute mutations were induced by P-element mutagenesis. Here, we report a previously undescribed Minute locus that maps to 32A on chromosome 2L; this Minute allele is named P(lacW)M(2)32A{sup 1} and the gene M(2)32A. Flies heterozygous for P(lacW)M(2)32A{sup 1} have a medium Minute phenotype. The gene interrupted by the P-element insertion was cloned. Sequence analyses revealed that it encodes the Drosophila homologue of eukaryotic ribosomal protein S13. It is a single-copy gene and the level of RPS13 transcript is reduced to {approximately}50% in P(lacW)M(2)32A{sup 1} heterozygotes. Both transcript level and phenotype are restored to wild type by remobilizing the P element, demonstrating that the mutation is caused by insertion of the P-element construct. These results further strengthen the notion that Minutes encode ribosomal proteins and demonstrate the P-element mutagenesis is a fruitful approach to use in these studies. 47 refs., 7 figs.

  8. Mutations affecting expression of the rosy locus in Drosophila melanogaster

    SciTech Connect

    Lee, C.S.; Curtis, D.; McCarron, M.; Love, C.; Gray, M.; Bender, W.; Chovnick, A.

    1987-05-01

    The rosy locus in Drosophila melanogaster codes for the enzyme xanthine dehydrogenase (XDH). Previous studies defined a control element near the 5' end of the gene, where variant sites affected the amount of rosy mRNA and protein produced. The authors have determined the DNA sequence of this region from both genomic and cDNA clones, and from the ry/sup +10/ underproducer strain. This variant strain had many sequence differences, so that the site of the regulatory change could not be fixed. A mutagenesis was also undertaken to isolate new regulatory mutations. They induced 376 new mutations with 1-ethyl-1-nitrosourea (ENU) and screened them to isolate those that reduced the amount of XDH protein produced, but did not change the properties of the enzyme. Genetic mapping was used to find mutations located near the 5' end of the gene. DNA from each of seven mutants was cloned and sequenced through the 5' region. Mutant base changes were identified in all seven; they appear to affect splicing and translation of the rosy mRNA. In a related study, the genomic and cDNA sequences are extended through the 3' end of the gene; the combined sequences define the processing pattern of the rosy transcript and predict the amino acid sequence of XDH.

  9. Comparative molecular population genetics of phycoerythrin locus in Prochlorococcus.

    PubMed

    Zhao, Fangqing; Qin, Song

    2007-03-01

    As the only remainder type of phycobiliproteins in Prochlorococcus, the actual role of phycoerythrin still remains unknown. Previous studies revealed that two different forms of phycoerythrin gene were found in two ecotypes of Prochlorococcus that are specifically adapted to either high light (HL) or low light (LL) conditions. Here we analyze patterns of phycoerythrin nucleotide variation in the HL- and LL-Prochlorococcus populations. Our analyses reveal a significantly greater number of non-synonymous fixed substitutions in peB and peA than expected based on interspecific comparisons. This pattern of excess non-synonymous fixed substitutions is not seen in other five phycoerythrin-related genes (peZ/V/Y/T/S). Several neutrality statistical tests indicate an excess of rare frequency polymorphisms in the LL-Prochlorococcus data, but an excess of intermediate frequency polymorphisms in the HL-Prochlorococcus data. Distributions of the positively selected sites identified using the likelihood ratio test, when mapped onto the phycoerythrin tertiary structure, reveal that HL- and LL-phycoerythrin should be under different selective patterns. These findings may provide insights into the likely role of selection at the phycoerythrin locus and motivate further research to unveil the function of phycoerythrin in Prochlorococcus. PMID:16897463

  10. The Lbw2 locus promotes autoimmune hemolytic anemia.

    PubMed

    Scatizzi, John C; Haraldsson, Maria K; Pollard, K Michael; Theofilopoulos, Argyrios N; Kono, Dwight H

    2012-04-01

    The lupus-prone New Zealand Black (NZB) strain uniquely develops a genetically imposed severe spontaneous autoimmune hemolytic anemia (AIHA) that is very similar to the corresponding human disease. Previous studies have mapped anti-erythrocyte Ab (AEA)-promoting NZB loci to several chromosomal locations, including chromosome 4; however, none of these have been analyzed with interval congenics. In this study, we used NZB.NZW-Lbw2 congenic (designated Lbw2 congenic) mice containing an introgressed fragment of New Zealand White (NZW) on chromosome 4 encompassing Lbw2, a locus previously linked to survival, glomerulonephritis, and splenomegaly, to investigate its role in AIHA. Lbw2 congenic mice exhibited marked reductions in AEAs and splenomegaly but not in anti-nuclear Abs. Furthermore, Lbw2 congenics had greater numbers of marginal zone B cells and reduced expansion of peritoneal cells, particularly the B-1a cell subset at early ages, but no reduction in B cell response to LPS. Analysis of a panel of subinterval congenic mice showed that the full effect of Lbw2 on AEA production was dependent on three subloci, with splenomegaly mapping to two of the subloci and expansions of peritoneal cell populations, including B-1a cells to one. These results directly demonstrated the presence of AEA-specific promoting genes on NZB chromosome 4, documented a marked influence of background genes on autoimmune phenotypes related to Lbw2, and further refined the locations of the underlying genetic variants. Delineation of the Lbw2 genes should yield new insights into both the pathogenesis of AIHA and the nature of epistatic interactions of lupus-modifying genetic variants.

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

    SciTech Connect

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

    1994-09-01

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

  12. Planetary maps

    USGS Publications Warehouse

    ,

    1992-01-01

    An important goal of the USGS planetary mapping program is to systematically map the geology of the Moon, Mars, Venus, and Mercury, and the satellites of the outer planets. These geologic maps are published in the USGS Miscellaneous Investigations (I) Series. Planetary maps on sale at the USGS include shaded-relief maps, topographic maps, geologic maps, and controlled photomosaics. Controlled photomosaics are assembled from two or more photographs or images using a network of points of known latitude and longitude. The images used for most of these planetary maps are electronic images, obtained from orbiting television cameras, various optical-mechanical systems. Photographic film was only used to map Earth's Moon.

  13. Transcription of the Drosophila white locus and some of its mutants.

    PubMed Central

    Pirrotta, V; Bröckl, C

    1984-01-01

    The white locus produces one major, though rare, RNA of 2.6 kb, found throughout development. Minor species of lower mol. wt. are also produced. One of these is male specific. Transcription was analysed by Northern blot hybridisation in the wild-type and several mutants: wa, w67c23, we, wsp and zeste. These and the results of S1 mapping reveal the presence of at least four introns. One of these, a micro-intron of 30-50 nucleotides contains the site of copia insertion in the wa mutant. Images Fig. 1. Fig. 2. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6425054

  14. Design and sample-size considerations in the detection of linkage disequilibrium with a disease locus

    SciTech Connect

    Olson, J.M.; Wijsman, E.M.

    1994-09-01

    The presence of linkage disequilibrium between closely linked loci can aid in the fine mapping of disease loci. The authors investigate the power of several designs for sampling individuals with different disease genotypes. As expected, haplotype data provide the greatest power for detecting disequilibrium, but, in the absence of parental information to resolve the phase of double heterozygotes, the most powerful design samples only individuals homozygous at the trait locus. For rare diseases, such a scheme is generally not feasible, and the authors also provide power and sample-size calculations for designs that sample heterozygotes. The results provide information useful in planning disequilibrium studies. 17 refs., 3 figs., 4 tabs.

  15. A nonclassical MHC class I U lineage locus in zebrafish with a null haplotypic variant

    PubMed Central

    Dirscherl, Hayley; Yoder, Jeffrey A.

    2015-01-01

    Three sequence lineages of MHC class I genes have been described in zebrafish (Danio rerio): U, Z, and L. The U lineage genes encoded on zebrafish chromosome 19 are predicted to provide the classical function of antigen presentation. This MHC class I locus displays significant haplotypic variation and is the only MHC class I locus in zebrafish that shares conserved synteny with the core mammalian MHC. Here we describe two MHC class I U lineage genes, mhc1ula and mhc1uma, that map to chromosome 22. Unlike the U lineage proteins encoded on chromosome 19, Ula and Uma likely play a nonclassical role as they lack conservation of key peptide binding residues, display limited polymorphic variation, and exhibit tissue-specific expression. We also describe a null haplotype at this chromosome 22 locus in which the mhc1ula and mhc1uma genes are absent due to a ∼30 kb deletion with no other MHC class I sequences present. Functional and non-functional transcripts of mhc1ula and mhc1uma were identified; however, mhc1uma transcripts were often not amplified or amplified at low levels from individuals possessing an apparently bona fide gene. These distinct U lineage genes may be restricted to the superorder Ostariophysi as similar sequences only could be identified from the blind cavefish (Astyanyx mexicanus), fathead minnow (Pimephales promelas), goldfish (Carassius auratus), and grass carp (Ctenopharyngodon idellus). PMID:26254596

  16. A nonclassical MHC class I U lineage locus in zebrafish with a null haplotypic variant.

    PubMed

    Dirscherl, Hayley; Yoder, Jeffrey A

    2015-09-01

    Three sequence lineages of MHC class I genes have been described in zebrafish (Danio rerio): U, Z, and L. The U lineage genes encoded on zebrafish chromosome 19 are predicted to provide the classical function of antigen presentation. This MHC class I locus displays significant haplotypic variation and is the only MHC class I locus in zebrafish that shares conserved synteny with the core mammalian MHC. Here, we describe two MHC class I U lineage genes, mhc1ula and mhc1uma, that map to chromosome 22. Unlike the U lineage proteins encoded on chromosome 19, Ula and Uma likely play a nonclassical role as they lack conservation of key peptide binding residues, display limited polymorphic variation, and exhibit tissue-specific expression. We also describe a null haplotype at this chromosome 22 locus in which the mhc1ula and mhc1uma genes are absent due to a ~30 kb deletion with no other MHC class I sequences present. Functional and non-functional transcripts of mhc1ula and mhc1uma were identified; however, mhc1uma transcripts were often not amplified or amplified at low levels from individuals possessing an apparently bona fide gene. These distinct U lineage genes may be restricted to the superorder Ostariophysi as similar sequences only could be identified from the blind cavefish (Astyanax mexicanus), fathead minnow (Pimephales promelas), goldfish (Carassius auratus), and grass carp (Ctenopharyngodon idella). PMID:26254596

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

    SciTech Connect

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

    1996-01-15

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

  18. Cytogenetic Analysis of Segregation Distortion in Drosophila Melanogaster: The Cytological Organization of the Responder (Rsp) Locus

    PubMed Central

    Pimpinelli, S.; Dimitri, P.

    1989-01-01

    The segregation distortion phenomenon occurs in Drosophila melanogaster males carrying an SD second chromosome and an SD(+) homolog. In such males the SD chromosome is transmitted to the progeny more frequently than the expected 50% because of an abnormal differentiation of the SD(+)-bearing sperms. Three major loci are involved in this phenomenon: SD and Rsp, associated with the SD and SD(+) chromosome, respectively, and E(SD). In the present work we performed a cytogenetic analysis of the Rsp locus which was known to map to the centromeric heterochromatin of the second chromosome. Hoechst- and N-banding techniques were used to characterize chromosomes carrying Responder insensitive (Rsp(i)), Responder sensitive (Rsp(s)) and Responder supersensitive (Rsp(ss)) alleles. Our results locate the Rsp locus to the h39 region of 2R heterochromatin. This region is a Hoechstbright, N-banding negative heterochromatic block adjacent to the centromere. Quantitative variations of the h39 region were observed. The degree of sensitivity to Sd was found to be directly correlated with the physical size of that region, demonstrating that the Rsp locus is composed of repeated DNA. PMID:2470640

  19. The MTAP-CDKN2A Locus Confers Susceptibility to a Naturally Occurring Canine Cancer

    PubMed Central

    Shearin, Abigail L.; Hedan, Benoit; Cadieu, Edouard; Erich, Suzanne A.; Schmidt, Emmett V.; Faden, Daniel L.; Cullen, John; Abadie, Jerome; Kwon, Erika M.; Gröne, Andrea; Devauchelle, Patrick; Rimbault, Maud; Karyadi, Danielle M.; Lynch, Mary; Galibert, Francis; Breen, Matthew; Rutteman, Gerard R.; André, Catherine; Parker, Heidi G.; Ostrander, Elaine A.

    2012-01-01

    Background Advantages offered by canine population substructure, combined with clinical presentations similar to human disorders, makes the dog an attractive system for studies of cancer genetics. Cancers that have been difficult to study in human families or populations are of particular interest. Histiocytic sarcoma is a rare and poorly understood neoplasm in humans that occurs in 15–25% of Bernese Mountain Dogs (BMD). Methods Genomic DNA was collected from affected and unaffected BMD in North America (NA) and Europe. Both independent and combined genome wide association studies (GWAS) were used to identify cancer-associated loci. Fine mapping and sequencing narrowed the primary locus to a single gene region. Results Both populations shared the same primary locus, which features a single haplotype spanning MTAP and part of CDKN2A and is present in 96% of affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in several types of cancer. Conclusions We present the first GWAS for HS in any species. The data identify an associated haplotype in the highly cited tumor suppressor locus near CDKN2A. These data demonstrate the power of studying distinctive malignancies in highly predisposed dog breeds. Impact Here, we establish a naturally-occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight regarding this cancer-associated, complex, and poorly understood genomic region. PMID:22623710

  20. Quantitative Trait Locus and Genetical Genomics Analysis Identifies Putatively Causal Genes for Fecundity and Brooding in the Chicken.

    PubMed

    Johnsson, Martin; Jonsson, Kenneth B; Andersson, Leif; Jensen, Per; Wright, Dominic

    2015-12-04

    Life history traits such as fecundity are important to evolution because they make up components of lifetime fitness. Due to their polygenic architectures, such traits are difficult to investigate with genetic mapping. Therefore, little is known about their molecular basis. One possible way toward finding the underlying genes is to map intermediary molecular phenotypes, such as gene expression traits. We set out to map candidate quantitative trait genes for egg fecundity in the chicken by combining quantitative trait locus mapping in an advanced intercross of wild by domestic chickens with expression quantitative trait locus mapping in the same birds. We measured individual egg fecundity in 232 intercross chickens in two consecutive trials, the second one aimed at measuring brooding. We found 12 loci for different aspects of egg fecundity. We then combined the genomic confidence intervals of these loci with expression quantitative trait loci from bone and hypothalamus in the same intercross. Overlaps between egg loci and expression loci, and trait-gene expression correlations identify 29 candidates from bone and five from hypothalamus. The candidate quantitative trait genes include fibroblast growth factor 1, and mitochondrial ribosomal proteins L42 and L32. In summary, we found putative quantitative trait genes for egg traits in the chicken that may have been affected by regulatory variants under chicken domestication. These represent, to the best of our knowledge, some of the first candidate genes identified by genome-wide mapping for life history traits in an avian species.

  1. Quantitative Trait Locus and Genetical Genomics Analysis Identifies Putatively Causal Genes for Fecundity and Brooding in the Chicken.

    PubMed

    Johnsson, Martin; Jonsson, Kenneth B; Andersson, Leif; Jensen, Per; Wright, Dominic

    2016-02-01

    Life history traits such as fecundity are important to evolution because they make up components of lifetime fitness. Due to their polygenic architectures, such traits are difficult to investigate with genetic mapping. Therefore, little is known about their molecular basis. One possible way toward finding the underlying genes is to map intermediary molecular phenotypes, such as gene expression traits. We set out to map candidate quantitative trait genes for egg fecundity in the chicken by combining quantitative trait locus mapping in an advanced intercross of wild by domestic chickens with expression quantitative trait locus mapping in the same birds. We measured individual egg fecundity in 232 intercross chickens in two consecutive trials, the second one aimed at measuring brooding. We found 12 loci for different aspects of egg fecundity. We then combined the genomic confidence intervals of these loci with expression quantitative trait loci from bone and hypothalamus in the same intercross. Overlaps between egg loci and expression loci, and trait-gene expression correlations identify 29 candidates from bone and five from hypothalamus. The candidate quantitative trait genes include fibroblast growth factor 1, and mitochondrial ribosomal proteins L42 and L32. In summary, we found putative quantitative trait genes for egg traits in the chicken that may have been affected by regulatory variants under chicken domestication. These represent, to the best of our knowledge, some of the first candidate genes identified by genome-wide mapping for life history traits in an avian species. PMID:26637433

  2. Quantitative Trait Locus and Genetical Genomics Analysis Identifies Putatively Causal Genes for Fecundity and Brooding in the Chicken

    PubMed Central

    Johnsson, Martin; Jonsson, Kenneth B.; Andersson, Leif; Jensen, Per; Wright, Dominic

    2015-01-01

    Life history traits such as fecundity are important to evolution because they make up components of lifetime fitness. Due to their polygenic architectures, such traits are difficult to investigate with genetic mapping. Therefore, little is known about their molecular basis. One possible way toward finding the underlying genes is to map intermediary molecular phenotypes, such as gene expression traits. We set out to map candidate quantitative trait genes for egg fecundity in the chicken by combining quantitative trait locus mapping in an advanced intercross of wild by domestic chickens with expression quantitative trait locus mapping in the same birds. We measured individual egg fecundity in 232 intercross chickens in two consecutive trials, the second one aimed at measuring brooding. We found 12 loci for different aspects of egg fecundity. We then combined the genomic confidence intervals of these loci with expression quantitative trait loci from bone and hypothalamus in the same intercross. Overlaps between egg loci and expression loci, and trait–gene expression correlations identify 29 candidates from bone and five from hypothalamus. The candidate quantitative trait genes include fibroblast growth factor 1, and mitochondrial ribosomal proteins L42 and L32. In summary, we found putative quantitative trait genes for egg traits in the chicken that may have been affected by regulatory variants under chicken domestication. These represent, to the best of our knowledge, some of the first candidate genes identified by genome-wide mapping for life history traits in an avian species. PMID:26637433

  3. Fine mapping of a dominant gene conferring chlorophyll-deficiency in Brassica napus

    PubMed Central

    Wang, Yankun; He, Yongjun; Yang, Mao; He, Jianbo; Xu, Pan; Shao, Mingquan; Chu, Pu; Guan, Rongzhan

    2016-01-01

    Leaf colour regulation is important in photosynthesis and dry material production. Most of the reported chlorophyll-deficient loci are recessive. The dominant locus is rarely reported, although it may be more important than the recessive locus in the regulation of photosynthesis efficiency. During the present study, we mapped a chlorophyll-deficient dominant locus (CDE1) from the ethyl methanesulfonate-mutagenized Brassica napus line NJ7982. Using an F2 population derived from the chlorophyll-deficient mutant (cde1) and the canola variety ‘zhongshuang11’, a high-density linkage map was constructed, consisting of 19 linkage groups with 2,878 bins containing 13,347 SNP markers, with a total linkage map length of 1,968.6 cM. Next, the CDE1 locus was mapped in a 0.9-cM interval of chromosome C08 of B. napus, co-segregating with nine SNP markers. In the following fine-mapping of the gene using the inherited F2:3 populations of 620 individuals, the locus was identified in an interval with a length of 311 kb. A bioinformatics analysis revealed that the mapping interval contained 22 genes. These results produced a good foundation for continued research on the dominant locus involved in chlorophyll content regulation. PMID:27506952

  4. Fine mapping of a dominant gene conferring chlorophyll-deficiency in Brassica napus.

    PubMed

    Wang, Yankun; He, Yongjun; Yang, Mao; He, Jianbo; Xu, Pan; Shao, Mingquan; Chu, Pu; Guan, Rongzhan

    2016-01-01

    Leaf colour regulation is important in photosynthesis and dry material production. Most of the reported chlorophyll-deficient loci are recessive. The dominant locus is rarely reported, although it may be more important than the recessive locus in the regulation of photosynthesis efficiency. During the present study, we mapped a chlorophyll-deficient dominant locus (CDE1) from the ethyl methanesulfonate-mutagenized Brassica napus line NJ7982. Using an F2 population derived from the chlorophyll-deficient mutant (cde1) and the canola variety 'zhongshuang11', a high-density linkage map was constructed, consisting of 19 linkage groups with 2,878 bins containing 13,347 SNP markers, with a total linkage map length of 1,968.6 cM. Next, the CDE1 locus was mapped in a 0.9-cM interval of chromosome C08 of B. napus, co-segregating with nine SNP markers. In the following fine-mapping of the gene using the inherited F2:3 populations of 620 individuals, the locus was identified in an interval with a length of 311 kb. A bioinformatics analysis revealed that the mapping interval contained 22 genes. These results produced a good foundation for continued research on the dominant locus involved in chlorophyll content regulation. PMID:27506952

  5. Externality and Locus of Control in Obese Children.

    ERIC Educational Resources Information Center

    Isbitsky, Joyce Renee; White, Donna Romano

    1981-01-01

    Significant sex differences indicated that boys generally ate more than girls and held more internal locus of control expectancies. However, obese and normal-weighted children were not differentiated by their performance on either food-related measures nor by their locus of control expectancies. (Author/MP)

  6. Anxiety, locus of control and appraisal of air pollution

    SciTech Connect

    Navarro, P.L.; Simpson-Housley, P.; de Man, A.F.

    1987-06-01

    100 residents of Santiago de Chile took part in a study of the relationship among locus of control, trait-anxiety, and perception of air pollution. Concern over the problem of atmospheric pollution and number of antipollution measures taken was related to trait-anxiety. Locus of control was associated with variation in awareness of pollution hazard.

  7. Locus of Control in Underachieving and Achieving Gifted Students.

    ERIC Educational Resources Information Center

    McClelland, Robert; And Others

    1991-01-01

    This study, with 87 underachieving and 77 achieving gifted students in grades 6-9, found that general locus of control measures did not differentiate between the 2 groups, that both scored significantly higher on positive internal than on negative internal locus of control, and that there were no gender or grade effects. (Author/DB)

  8. Locus of Control and Marital Stability: A Longitudinal Study.

    ERIC Educational Resources Information Center

    Constantine, John A.; Bahr, Stephen J.

    1980-01-01

    Investigated relationship between locus of control and marital stability of young men. Factors derived from locus of control measures included leadership, personal, and fate scales. Results indicated the only significant difference was on the leadership scale between men remaining married and those who did not. (RC)

  9. Personality and Locus of Control among School Children

    ERIC Educational Resources Information Center

    Pandya, Archana A.; Jogsan, Yogesh A.

    2013-01-01

    The main purpose of this investigation is to find out the sex differences in personality traits and locus of control among school children. A total 60 children (30 boys and 30 girls) were taken as a sample. The research tool for personality, children personality questionnaire was used, which was made by Cattell and Porter. Locus of control was…

  10. 40 CFR 798.5200 - Mouse visible specific locus test.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... result, one of which is a statistically significant dose-related increase in the number of specific locus... a statistically significant dose-related increase in the number of specific locus mutations or a... eukaryotes which are the carriers of the genetic information for the species. (c) Reference......

  11. The Cajal Body and Histone Locus Body

    PubMed Central

    Nizami, Zehra; Deryusheva, Svetlana; Gall, Joseph G.

    2010-01-01

    The Cajal body (CB) is a nuclear organelle present in all eukaryotes that have been carefully studied. It is identified by the signature protein coilin and by CB-specific RNAs (scaRNAs). CBs contain high concentrations of splicing small nuclear ribonucleoproteins (snRNPs) and other RNA processing factors, suggesting that they are sites for assembly and/or posttranscriptional modification of the splicing machinery of the nucleus. The histone locus body (HLB) contains factors required for processing histone pre-mRNAs. As its name implies, the HLB is associated with the genes that code for histones, suggesting that it may function to concentrate processing factors at their site of action. CBs and HLBs are present throughout the interphase of the cell cycle, but disappear during mitosis. The biogenesis of CBs shows the features of a self-organizing structure. PMID:20504965

  12. Identifying a novel locus for psoriatic arthritis

    PubMed Central

    Budu-Aggrey, Ashley; Bowes, John

    2016-01-01

    A number of studies have identified genetic risk loci for PsA, the majority of which also confer risk for psoriasis. The stronger heritability of PsA in comparison with psoriasis suggests that there should be risk loci that are specific for PsA. Identifying such loci could potentially inform therapy development to provide more effective treatments for PsA patients, especially with a considerable proportion being non-responsive to current therapies. Evidence of a PsA-specific locus has been previously found at HLA-B27 within the MHC region. A recent study has provided evidence of non-HLA risk loci that are specific for PsA at IL23R, PTPN22 and on chromosome 5q31. Functional characterization of these loci will provide further understanding of the pathways underlying PsA, and enable us to apply genetic findings for patient benefit. PMID:26255310

  13. Map accuracy

    USGS Publications Warehouse

    ,

    1981-01-01

    An inaccurate map is not a reliable map. "X" may mark the spot where the treasure is buried, but unless the seeker can locate "X" in relation to known landmarks or positions, the map is not very useful.

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

    SciTech Connect

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

    1994-09-01

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

  15. Single nucleotide polymorphisms in linkage disequilibrium with the male-fertility restoration (Ms) locus in open-pollinated and inbred populations of onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintainer lines are used to seed propagate male-sterile lines for the development of hybrid-onion cultivars. The identification of maintainer lines would be more efficient with molecular markers distinguishing genotypes at the nuclear male-fertility restoration (Ms) locus. Ms has been mapped to chr...

  16. Locus of Control Orientation: Parents, Peers, and Place.

    PubMed

    Ahlin, Eileen M; Lobo Antunes, Maria João

    2015-09-01

    An internal locus of control contributes to positive youth outcomes such as a general well-being and academic success, while also serving as a protective factor against exposure to community violence and reducing negative behaviors like violence. Despite these benefits, very little is known about antecedents of an internal locus of control orientation. Without an understanding of what factors contribute to the development of an internal locus of control, it is not clear how to best encourage its formation. This study uses data from the Project on Human Development in Chicago Neighborhoods to examine whether various mesosystem variables (family management strategies, peer interactions, neighborhood context, and individual-level characteristics) are associated with an internal locus of control orientation among 1,076 youth ages 9-19 living in 78 Chicago neighborhoods. Study participants were Hispanic (46 %), African American (34 %), and White (15 %), and 50 % were female. The findings suggest that, while most levels of the mesosystem influence locus of control orientation, family management strategies are more prominent determinants of an internal locus of control than peers, neighborhood context, or individual characteristics. Parental supervision over the time a youth spends at home and family socioeconomic status are consistent predictors of an internal locus of control, while harsh discipline is associated with an external locus of control. The discussion examines the import of various parenting techniques in shaping an internal locus of control and considers future avenues for research to further unpack how antecedents of locus of control can vary across youth. PMID:25617000

  17. Locus of Control Orientation: Parents, Peers, and Place.

    PubMed

    Ahlin, Eileen M; Lobo Antunes, Maria João

    2015-09-01

    An internal locus of control contributes to positive youth outcomes such as a general well-being and academic success, while also serving as a protective factor against exposure to community violence and reducing negative behaviors like violence. Despite these benefits, very little is known about antecedents of an internal locus of control orientation. Without an understanding of what factors contribute to the development of an internal locus of control, it is not clear how to best encourage its formation. This study uses data from the Project on Human Development in Chicago Neighborhoods to examine whether various mesosystem variables (family management strategies, peer interactions, neighborhood context, and individual-level characteristics) are associated with an internal locus of control orientation among 1,076 youth ages 9-19 living in 78 Chicago neighborhoods. Study participants were Hispanic (46 %), African American (34 %), and White (15 %), and 50 % were female. The findings suggest that, while most levels of the mesosystem influence locus of control orientation, family management strategies are more prominent determinants of an internal locus of control than peers, neighborhood context, or individual characteristics. Parental supervision over the time a youth spends at home and family socioeconomic status are consistent predictors of an internal locus of control, while harsh discipline is associated with an external locus of control. The discussion examines the import of various parenting techniques in shaping an internal locus of control and considers future avenues for research to further unpack how antecedents of locus of control can vary across youth.

  18. Disequilibrium mapping: Composite likelihood for pairwise disequilibrium

    SciTech Connect

    Devlin, B.; Roeder, K.; Risch, N.

    1996-08-15

    The pattern of linkage disequilibrium between a disease locus and a set of marker loci has been shown to be a useful tool for geneticists searching for disease genes. Several methods have been advanced to utilize the pairwise disequilibrium between the disease locus and each of a set of marker loci. However, none of the methods take into account the information from all pairs simultaneously while also modeling the variability in the disequilibrium values due to the evolutionary dynamics of the population. We propose a Composite Likelihood CL model that has these features when the physical distances between the marker loci are known or can be approximated. In this instance, and assuming that there is a single disease mutation, the CL model depends on only three parameters, the recombination fraction between the disease locus and an arbitrary marker locus, {theta}, the age of the mutation, and a variance parameter. When the CL is maximized over a grid of {theta}, it provides a graph that can direct the search for the disease locus. We also show how the CL model can be generalized to account for multiple disease mutations. Evolutionary simulations demonstrate the power of the analyses, as well as their potential weaknesses. Finally, we analyze the data from two mapped diseases, cystic fibrosis and diastrophic dysplasia, finding that the CL method performs well in both cases. 28 refs., 6 figs., 4 tabs.

  19. An S-locus independent pollen factor confers self-compatibility in 'Katy' apricot.

    PubMed

    Zuriaga, Elena; Muñoz-Sanz, Juan V; Molina, Laura; Gisbert, Ana D; Badenes, María L; Romero, Carlos

    2013-01-01

    Loss of pollen-S function in Prunus self-compatible cultivars has been mostly associated with deletions or insertions in the S-haplotype-specific F-box (SFB) genes. However, self-compatible pollen-part mutants defective for non-S-locus factors have also been found, for instance, in the apricot (Prunus armeniaca) cv. 'Canino'. In the present study, we report the genetic and molecular analysis of another self-compatible apricot cv. termed 'Katy'. S-genotype of 'Katy' was determined as S(1)S(2) and S-RNase PCR-typing of selfing and outcrossing populations from 'Katy' showed that pollen gametes bearing either the S(1)- or the S(2)-haplotype were able to overcome self-incompatibility (SI) barriers. Sequence analyses showed no SNP or indel affecting the SFB(1) and SFB(2) alleles from 'Katy' and, moreover, no evidence of pollen-S duplication was found. As a whole, the obtained results are compatible with the hypothesis that the loss-of-function of a S-locus unlinked factor gametophytically expressed in pollen (M'-locus) leads to SI breakdown in 'Katy'. A mapping strategy based on segregation distortion loci mapped the M'-locus within an interval of 9.4 cM at the distal end of chr.3 corresponding to ∼1.29 Mb in the peach (Prunus persica) genome. Interestingly, pollen-part mutations (PPMs) causing self-compatibility (SC) in the apricot cvs. 'Canino' and 'Katy' are located within an overlapping region of ∼273 Kb in chr.3. No evidence is yet available to discern if they affect the same gene or not, but molecular markers seem to indicate that both cultivars are genetically unrelated suggesting that every PPM may have arisen independently. Further research will be necessary to reveal the precise nature of 'Katy' PPM, but fine-mapping already enables SC marker-assisted selection and paves the way for future positional cloning of the underlying gene.

  20. An S-Locus Independent Pollen Factor Confers Self-Compatibility in ‘Katy’ Apricot

    PubMed Central

    Molina, Laura; Gisbert, Ana D.; Badenes, María L.; Romero, Carlos

    2013-01-01

    Loss of pollen-S function in Prunus self-compatible cultivars has been mostly associated with deletions or insertions in the S-haplotype-specific F-box (SFB) genes. However, self-compatible pollen-part mutants defective for non-S-locus factors have also been found, for instance, in the apricot (Prunus armeniaca) cv. ‘Canino’. In the present study, we report the genetic and molecular analysis of another self-compatible apricot cv. termed ‘Katy’. S-genotype of ‘Katy’ was determined as S1S2 and S-RNase PCR-typing of selfing and outcrossing populations from ‘Katy’ showed that pollen gametes bearing either the S1- or the S2-haplotype were able to overcome self-incompatibility (SI) barriers. Sequence analyses showed no SNP or indel affecting the SFB1 and SFB2 alleles from ‘Katy’ and, moreover, no evidence of pollen-S duplication was found. As a whole, the obtained results are compatible with the hypothesis that the loss-of-function of a S-locus unlinked factor gametophytically expressed in pollen (M’-locus) leads to SI breakdown in ‘Katy’. A mapping strategy based on segregation distortion loci mapped the M’-locus within an interval of 9.4 cM at the distal end of chr.3 corresponding to ∼1.29 Mb in the peach (Prunus persica) genome. Interestingly, pollen-part mutations (PPMs) causing self-compatibility (SC) in the apricot cvs. ‘Canino’ and ‘Katy’ are located within an overlapping region of ∼273 Kb in chr.3. No evidence is yet available to discern if they affect the same gene or not, but molecular markers seem to indicate that both cultivars are genetically unrelated suggesting that every PPM may have arisen independently. Further research will be necessary to reveal the precise nature of ‘Katy’ PPM, but fine-mapping already enables SC marker-assisted selection and paves the way for future positional cloning of the underlying gene. PMID:23342044

  1. Adenovirus cyt+ locus, which controls cell transformation and tumorigenicity, is an allele of lp+ locus, which codes for a 19-kilodalton tumor antigen.

    PubMed Central

    Subramanian, T; Kuppuswamy, M; Mak, S; Chinnadurai, G

    1984-01-01

    The early region E1b of adenovirus type 2 (Ad2) codes for two major tumor antigens of 53 and 19 kilodaltons (kd). The adenovirus lp+ locus maps within the 19-kd tumor antigen-coding region (G. Chinnadurai, Cell 33:759-766, 1983). We have now constructed a large-plaque deletion mutant (dl250) of Ad2 that has a specific lesion in the 19-kd tumor antigen-coding region. In contrast to most other Ad2 lp mutants (G. Chinnadurai, Cell 33:759-766, 1983), mutant dl250 is cytocidal (cyt) on infected KB cells, causing extensive cellular destruction. Cells infected with Ad2 wt or most of these other Ad2 lp mutants are rounded and aggregated without cell lysis (cyt+). The cyt phenotype of dl250 resembles the cyt mutants of highly oncogenic Ad12, isolated by Takemori et al. (Virology 36:575-586, 1968). By intertypic complementation analysis, we showed that the Ad12 cyt mutants indeed map within the 19-kd tumor antigen-coding region. The transforming potential of dl250 was assayed on an established rat embryo fibroblast cell line, CREF, and on primary rat embryo fibroblasts and baby rat kidney cells. On all these cells, dl250 induced transformation at greatly reduced frequency compared with wt. The cells transformed by this mutant are defective in anchorage-independent growth on soft agar. Our results suggest that the 19-kd tumor antigen (in conjunction with E1a tumor antigens) may play an important role in the maintenance of cell transformation. Since we have mapped the low-oncogenic or nononcogenic Ad12 cyt mutants within the 19-kd tumor antigen-coding region, our results further indicate that the 19-kd tumor antigen also directly or indirectly plays an important role in tumorigenesis of Ad12. Our results show that the cyt+ locus is an allele of the lp+ locus and that the cyt phenotype may be the result of mutations in specific domains of the 19-kd tumor antigen. Images PMID:6492253

  2. Identification of Potentially Pathogenic Variants in the Posterior Polymorphous Corneal Dystrophy 1 Locus

    PubMed Central

    Le, Derek J.; Chung, Duk-Won D.; Frausto, Ricardo F.; Kim, Michelle J.; Aldave, Anthony J.

    2016-01-01

    Posterior polymorphous corneal dystrophy 1 (PPCD1) is a genetic disorder that affects corneal endothelial cell function and leads to loss of visual acuity. PPCD1 has been linked to a locus on chromosome 20 in multiple families; however, Sanger sequencing of protein-coding genes in the consensus region failed to identify any causative missense mutations. In this study, custom capture probes were utilized for targeted next-generation sequencing of the linked region in a previously reported family with PPCD1. Variants were detected through two bioinformatics pipelines and filtered according to multiple criteria. Additionally, a high-resolution microarray was used to detect copy number variations. No non-synonymous variants in the protein-coding region of annotated genes were identified. However, 12 single nucleotide variants in 10 genes, and 9 indels in 7 genes met the filtering criteria and were considered candidate variants for PPCD1. Eleven single nucleotide variants were confirmed by Sanger sequencing, including 2 synonymous variants and 9 non-coding variants, in 9 genes. One microdeletion was detected in an intron of OVOL2 by microarray but was subsequently not identified by PCR. Using a comprehensive next-generation sequencing approach, a total of 16 genes containing single nucleotide variants or indels that segregated with the affected phenotype in an affected family previously mapped to the PPCD1 locus were identified. Screening of these candidate genes in other families previously mapped to the PPCD1 locus will likely result in the identification of the genetic basis of PPCD1. PMID:27355326

  3. Candidate regions for Waardenburg syndrome type II: Search for a second WS locus

    SciTech Connect

    Nance, W.E.; Pandya, A.; Blanton, S.H.

    1994-09-01

    Waardenburg syndrome is an autosomal dominant disorder characterized by deafness and pigmentary abnormalities such as heterochromia of irides, hypopigmented skin patches, white forlock and premature graying. Clinically the syndrome has been classified into three types. Type II differs from type I in that dystopia canthorum is generally absent, and type III has associated limb anomalies. Recently linkage analysis localized the gene for WSI to chromosome 2q. PAX-3, which is a human analogue of the murine pax-3 locus, maps to this region and mutations in this gene have been found to segregate with WSI. However genetic heterogeneity clearly exists: most if not all WSII families are unlinked to PAX-3 while most if not all WSI cases are linked. We ascertained a four-year-old female child with an interstitial deletion of chromosome 13 who had features of WS including bilateral congenital sensorineural hearing loss, pale blue irides and pinched nostrils as well as hypertelorism microcephaly, bilateral eyelid ptosis, digitalization of thumbs and fifth finger clinodactyly. High resolution chromosomal analysis revealed a de novo interstitial deletion of 13q22-33.2. There was no family history of WS or retardation. A similar deletion in the region of 13q21-32 has been described in a 13-year-old boy with features of WSII. These two cases strongly suggested that this chromosomal region may include a second locus for WS. We have identified eight families with clinical features of WS type I which have been excluded from linkage to the PAX-3 locus. We have typed these families for microsatellite markers spanning chromosome 13. Linkage between WSII and the chromosome 13 markers was excluded in these families. Hirschsprung disease has been associated with WS and it has recently been mapped to chromosome 10q11.2-q21.1. We are currently typing the 8 families for microsatellites in this region.

  4. Exploring maps

    USGS Publications Warehouse

    ,

    1993-01-01

    Exploring Maps is an interdisciplinary set of materials on mapping for grades 7-12. Students will learn basic mapmaking and map reading skills and will see how maps can answer fundamental geographic questions: "Where am I?" "What else is here?" "Where am I going?"

  5. Low Cost Upper Atmosphere Sounder (LOCUS)

    NASA Astrophysics Data System (ADS)

    Gerber, Daniel; Swinyard, Bruce M.; Ellison, Brian N.; Aylward, Alan D.; Aruliah, Anasuya; Plane, John M. C.; Feng, Wuhu; Saunders, Christopher; Friend, Jonathan; Bird, Rachel; Linfield, Edmund H.; Davies, A. Giles; Parkes, Steve

    2014-05-01

    near future. We describe the current instrument configuration of LOCUS, and give a first preview of the expected science return such a mission would yield. The LOCUS instrument concept calls for four spectral bands, a first band at 4.7 THz to target atomic oxygen (O), a second band at 3.5 THz to target hydroxyl (OH), a third band at 1.1 THz to cover several diatomic species (NO, CO, O3, H2O) and finally a fourth band at 0.8 THz to retrieve pointing information from molecular oxygen (O2). LOCUS would be the first satellite instrument to measure atomic oxygen on a global scale with a precision that will allow the retrieval of the global O distribution. It would also be the first time that annual and diurnal changes in O are measured. This will be a significant step forward in understanding the chemistry and dynamics of the MLT. Current indications (derived from CRISTA measurement) lead us to believe that current models only give a poor representation of upper atmospheric O. The secondary target species can help us to address additional scientific questions related to both Climate (distribution of climate relevant gases, highly geared cooling of the MLT in response to Climate change, increased occurrence of Polar Mesospheric Clouds (PMC), etc) and Space Weather (precipitation of electrically charged particles and impact on NOx chemistry, fluctuations of solar Lyman-alpha flux through shown in the the distribution of photochemically active species, etc).

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

    SciTech Connect

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

    1994-09-01

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

  7. Contour Mapping

    NASA Technical Reports Server (NTRS)

    1995-01-01

    In the early 1990s, the Ohio State University Center for Mapping, a NASA Center for the Commercial Development of Space (CCDS), developed a system for mobile mapping called the GPSVan. While driving, the users can map an area from the sophisticated mapping van equipped with satellite signal receivers, video cameras and computer systems for collecting and storing mapping data. George J. Igel and Company and the Ohio State University Center for Mapping advanced the technology for use in determining the contours of a construction site. The new system reduces the time required for mapping and staking, and can monitor the amount of soil moved.

  8. Locus-specific genetic differentiation at Rw among warfarin-resistant rat (Rattus norvegicus) populations.

    PubMed Central

    Kohn, Michael H; Pelz, Hans-Joachim; Wayne, Robert K

    2003-01-01

    Populations may diverge at fitness-related genes as a result of adaptation to local conditions. The ability to detect this divergence by marker-based genomic scans depends on the relative magnitudes of selection, recombination, and migration. We survey rat (Rattus norvegicus) populations to assess the effect that local selection with anticoagulant rodenticides has had on microsatellite marker variation and differentiation at the warfarin resistance gene (Rw) relative to the effect on the genomic background. Initially, using a small sample of 16 rats, we demonstrate tight linkage of microsatellite D1Rat219 to Rw by association mapping of genotypes expressing an anticoagulant-rodenticide-insensitive vitamin K 2,3-epoxide reductase (VKOR). Then, using allele frequencies at D1Rat219, we show that predicted and observed resistance levels in 27 populations correspond, suggesting intense and recent selection for resistance. A contrast of F(ST) values between D1Rat219 and the genomic background revealed that rodenticide selection has overwhelmed drift-mediated population structure only at Rw. A case-controlled design distinguished these locus-specific effects of selection at Rw from background levels of differentiation more effectively than a population-controlled approach. Our results support the notion that an analysis of locus-specific population genetic structure may assist the discovery and mapping of novel candidate loci that are the object of selection or may provide supporting evidence for previously identified loci. PMID:12871915

  9. A Novel High-Resolution Single Locus Sequence Typing Scheme for Mixed Populations of Propionibacterium acnes In Vivo

    PubMed Central

    Scholz, Christian F. P.; Jensen, Anders; Lomholt, Hans B.; Brüggemann, Holger; Kilian, Mogens

    2014-01-01

    The Gram-positive anaerobic bacterium Propionibacterium acnes is a prevalent member of the normal skin microbiota of human adults. In addition to its suspected role in acne vulgaris it is involved in a variety of opportunistic infections. Multi-locus sequence-typing (MLST) schemes identified distinct phylotypes associated with health and disease. Being based on 8 to 9 house-keeping genes these MLST schemes have a high discriminatory power, but their application is time- and cost-intensive. Here we describe a single-locus sequence typing (SLST) scheme for P. acnes. The target locus was identified with a genome mining approach that took advantage of the availability of representative genome sequences of all known phylotypes of P. acnes. We applied this SLST on a collection of 188 P. acnes strains and demonstrated a resolution comparable to that of existing MLST schemes. Phylogenetic analysis applied to the SLST locus resulted in clustering patterns identical to a reference tree based on core genome sequences. We further demonstrate that SLST can be applied to detect multiple phylotypes in complex microbial communities by a metagenomic pyrosequencing approach. The described SLST strategy may be applied to any bacterial species with a basically clonal population structure to achieve easy typing and mapping of multiple phylotypes in complex microbiotas. The P. acnes SLST database can be found at http://medbac.dk/slst/pacnes. PMID:25111794

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

    SciTech Connect

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

    1992-09-01

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

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

    SciTech Connect

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

    1995-05-01

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

  12. A soybean quantitative trait locus that promotes flowering under long days is identified as FT5a, a FLOWERING LOCUS T ortholog

    PubMed Central

    Takeshima, Ryoma; Hayashi, Takafumi; Zhu, Jianghui; Zhao, Chen; Xu, Meilan; Yamaguchi, Naoya; Sayama, Takashi; Ishimoto, Masao; Kong, Lingping; Shi, Xinyi; Liu, Baohui; Tian, Zhixi; Yamada, Tetsuya; Kong, Fanjiang; Abe, Jun

    2016-01-01

    FLOWERING LOCUS T (FT) is an important floral integrator whose functions are conserved across plant species. In soybean, two orthologs, FT2a and FT5a, play a major role in initiating flowering. Their expression in response to different photoperiods is controlled by allelic combinations at the maturity loci E1 to E4, generating variation in flowering time among cultivars. We determined the molecular basis of a quantitative trait locus (QTL) for flowering time in linkage group J (Chromosome 16). Fine-mapping delimited the QTL to a genomic region of 107kb that harbors FT5a. We detected 15 DNA polymorphisms between parents with the early-flowering (ef) and late-flowering (lf) alleles in the promoter region, an intron, and the 3′ untranslated region of FT5a, although the FT5a coding regions were identical. Transcript abundance of FT5a was higher in near-isogenic lines for ef than in those for lf, suggesting that different transcriptional activities or mRNA stability caused the flowering time difference. Single-nucleotide polymorphism (SNP) calling from re-sequencing data for 439 cultivated and wild soybean accessions indicated that ef is a rare haplotype that is distinct from common haplotypes including lf. The ef allele at FT5a may play an adaptive role at latitudes where early flowering is desirable. PMID:27422993

  13. A soybean quantitative trait locus that promotes flowering under long days is identified as FT5a, a FLOWERING LOCUS T ortholog.

    PubMed

    Takeshima, Ryoma; Hayashi, Takafumi; Zhu, Jianghui; Zhao, Chen; Xu, Meilan; Yamaguchi, Naoya; Sayama, Takashi; Ishimoto, Masao; Kong, Lingping; Shi, Xinyi; Liu, Baohui; Tian, Zhixi; Yamada, Tetsuya; Kong, Fanjiang; Abe, Jun

    2016-09-01

    FLOWERING LOCUS T (FT) is an important floral integrator whose functions are conserved across plant species. In soybean, two orthologs, FT2a and FT5a, play a major role in initiating flowering. Their expression in response to different photoperiods is controlled by allelic combinations at the maturity loci E1 to E4, generating variation in flowering time among cultivars. We determined the molecular basis of a quantitative trait locus (QTL) for flowering time in linkage group J (Chromosome 16). Fine-mapping delimited the QTL to a genomic region of 107kb that harbors FT5a We detected 15 DNA polymorphisms between parents with the early-flowering (ef) and late-flowering (lf) alleles in the promoter region, an intron, and the 3' untranslated region of FT5a, although the FT5a coding regions were identical. Transcript abundance of FT5a was higher in near-isogenic lines for ef than in those for lf, suggesting that different transcriptional activities or mRNA stability caused the flowering time difference. Single-nucleotide polymorphism (SNP) calling from re-sequencing data for 439 cultivated and wild soybean accessions indicated that ef is a rare haplotype that is distinct from common haplotypes including lf The ef allele at FT5a may play an adaptive role at latitudes where early flowering is desirable. PMID:27422993

  14. Role of TRAV Locus in Low Caries Experience

    PubMed Central

    Briseño-Ruiz, Jessica; Shimizu, Takehiko; Deeley, Kathleen; Dizak, Piper M.; Ruff, Timothy D.; Faraco, Italo M.; Poletta, Fernando A.; Brancher, João A.; Pecharki, Giovana D.; Küchler, Erika C.; Tannure, Patricia N.; Lips, Andrea; Vieira, Thays C.S.; Patir, Asli; Koruyucu, Mine; Mereb, Juan C.; Resick, Judith M.; Brandon, Carla A.; Letra, Ariadne; Silva, Renato M.; Cooper, Margaret E.; Seymen, Figen; Costa, Marcelo C.; Granjeiro, José M.; Trevilatto, Paula C.; Orioli, Iêda M.; Castilla, Eduardo E.; Marazita, Mary L.; Vieira, Alexandre R.

    2013-01-01

    Caries is the most common chronic, multifactorial disease in the world today; and little is still known about the genetic factors influencing susceptibility. Our previous genome- wide linkage scan has identified five loci related to caries susceptibility: 5q13.3, 13q31.1, 14q11.2, 14q 24.3, and Xq27. In the present study, we fine mapped the 14q11.2 locus in order to identify genetic contributors to caries susceptibility. Four hundred seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. An additional 387 DNA samples from unrelated individuals were used to determine allele frequencies. For replication purposes, a total of 1,446 independent subjects from four different populations were analyzed based on their caries experience (low versus high). Forty-eight markers in 14q11.2 were genotyped using TaqMan chemistry. Transmission disequilibrium test was used to detect overtransmission of alleles in the Filipino families, and chi-square, Fisher’s exact and logistic regression were used to test for association between low caries experience and variant alleles in the replication data sets. We finally assessed the mRNA expression of TRAV4 in the saliva of 143 study subjects. In the Filipino families, statistically significant associations were found between low caries experience and markers in TRAV4. We were able to replicate these results in the populations studied that were characteristically from underserved areas. Direct sequencing of 22 subjects carrying the associated alleles detect one missense mutation (Y30R) that is predicted to be probably damaging. Finally, we observed higher expression in children and teenagers with low caries experience, correlating with specific alleles in TRAV4. Our results suggest TRAV4 may have a role in protecting against caries. PMID:23657505

  15. ABI3 controls embryo degreening through Mendel's I locus

    PubMed Central

    Delmas, Frédéric; Sankaranarayanan, Subramanian; Deb, Srijani; Widdup, Ellen; Bournonville, Céline; Bollier, Norbert; Northey, Julian G. B.; McCourt, Peter; Samuel, Marcus A.

    2013-01-01

    Chlorophyll (chl) is essential for light capture and is the starting point that provides the energy for photosynthesis and thus plant growth. Obviously, for this reason, retention of the green chlorophyll pigment is considered a desirable crop trait. However, the presence of chlorophyll in mature seeds can be an undesirable trait that can affect seed maturation, seed oil quality, and meal quality. Occurrence of mature green seeds in oil crops such as canola and soybean due to unfavorable weather conditions during seed maturity is known to cause severe losses in revenue. One recently identified candidate that controls the chlorophyll degradation machinery is the stay-green gene, SGR1 that was mapped to Mendel’s I locus responsible for cotyledon color (yellow versus green) in peas. A defect in SGR1 leads to leaf stay-green phenotypes in Arabidopsis and rice, but the role of SGR1 in seed degreening and the signaling machinery that converges on SGR1 have remained elusive. To decipher the gene regulatory network that controls degreening in Arabidopsis, we have used an embryo stay-green mutant to demonstrate that embryo degreening is achieved by the SGR family and that this whole process is regulated by the phytohormone abscisic acid (ABA) through ABSCISIC ACID INSENSITIVE 3 (ABI3); a B3 domain transcription factor that has a highly conserved and essential role in seed maturation, conferring desiccation tolerance. Misexpression of ABI3 was sufficient to rescue cold-induced green seed phenotype in Arabidopsis. This finding reveals a mechanistic role for ABI3 during seed degreening and thus targeting of this pathway could provide a solution to the green seed problem in various oil-seed crops. PMID:24043799

  16. Genomic organization of the S-locus region of Brassica.

    PubMed

    Shiba, Hiroshi; Kenmochi, Masayuki; Sugihara, Minoru; Iwano, Megumi; Kawasaki, Shinji; Suzuki, Go; Watanabe, Masao; Isogai, Akira; Takayama, Seiji

    2003-03-01

    To gain some insights into the structure of the S-locus and the mechanisms that have kept its diversity, a 75-kb genomic fragment containing the self-incompatibility (S) locus region was isolated from the S12-haplotype of Brassica rapa and compared with those of other S-haplotypes. The region around the S determinant genes was highly polymorphic and filled with S-haplotype-specific intergenic sequences. The diverse genomic structure must contribute to the suppression of recombination at the S-locus.

  17. THE LOCUS COERULEUS AND CENTRAL CHEMOSENSITIVITY

    PubMed Central

    Gargaglioni, Luciane H.; Hartzler, Lynn K.; Putnam, Robert W.

    2010-01-01

    The locus coeruleus (LC) lies in the dorsal pons and supplies noradrenergic (NA) input to many regions of the brain, including respiratory control areas. The LC may provide tonic input for basal respiratory drive and is involved in central chemosensitivity since focal acidosis of the region stimulates ventilation and ablation reduces CO2-induced increased ventilation. The output of LC is modulated by both serotonergic and glutamatergic inputs. A large percentage of LC neurons are intrinsically activated by hypercapnia. This percentage and the magnitude of their response are highest in young neonates and decrease dramatically after postnatal day P10. The cellular bases for intrinsic chemosensitivity of LC neurons are comprised of multiple factors, primary among them being reduced extracellular and intracellular pH, which inhibit inwardly rectifying and voltage-gated K+ channels, and activate L-type Ca2+ channels. Activation of KCa channels in LC neurons may limit their ultimate response to hypercapnia. Finally, the LC mediates central chemosensitivity and contains pH-sensitive neurons in amphibians, suggesting that the LC has a long-standing phylogenetic role in respiratory control. PMID:20435170

  18. Sequence Variation Within the Fragile X Locus

    PubMed Central

    Mathews, Debra J.; Kashuk, Carl; Brightwell, Gale; Eichler, Evan E.; Chakravarti, Aravinda

    2001-01-01

    The human genome provides a reference sequence, which is a template for resequencing studies that aim to discover and interpret the record of common ancestry that exists in extant genomes. To understand the nature and pattern of variation and linkage disequilibrium comprising this history, we present a study of ∼31 kb spanning an ∼70 kb region of FMR1, sequenced in a sample of 20 humans (worldwide sample) and four great apes (chimp, bonobo, and gorilla). Twenty-five polymorphic sites and two insertion/deletions, distributed in 11 unique haplotypes, were identified among humans. Africans are the only geographic group that do not share any haplotypes with other groups. Parsimony analysis reveals two main clades and suggests that the four major human geographic groups are distributed throughout the phylogenetic tree and within each major clade. An African sample appears to be most closely related to the common ancestor shared with the three other geographic groups. Nucleotide diversity, π, for this sample is 2.63 ± 6.28 × 10−4. The mutation rate, μ, is 6.48 × 10−10 per base pair per year, giving an ancestral population size of ∼6200 and a time to the most recent common ancestor of ∼320,000 ± 72,000 per base pair per year. Linkage disequilibrium (LD) at the FMR1 locus, evaluated by conventional LD analysis and by the length of segment shared between any two chromosomes, is extensive across the region. PMID:11483579

  19. Chromosomal locus for staphylococcal enterotoxin B.

    PubMed Central

    Shafer, W M; Iandolo, J J

    1978-01-01

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

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

    SciTech Connect

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

    1996-04-15

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

  1. Organization of the Rosy Locus in DROSOPHILA MELANOGASTER: Further Evidence in Support of a CIS-Acting Control Element Adjacent to the Xanthine Dehydrogenase Structural Element

    PubMed Central

    McCarron, M.; O'Donnell, J.; Chovnick, A.; Bhullar, B. S.; Hewitt, J.; Candido, E. P. M.

    1979-01-01

    The present report summarizes our recent progress in the genetic dissection of an elementary genetic unit in a higher organism, the rosy locus (ry:3–52.0) in Drosophila melanogaster. Pursuing the hypothesis that the rosy locus includes a noncoding control region, as well as a structural element coding for the xanthine dehydrogenase (XDH) peptide, experiments are described that characterize and map a rosy locus variant associated with much lower than normal levels of XDH activity. Experiments are described that fail to relate this phenotype to alteration in the structure of the XDH peptide, but clearly associate this character with variation in number of molecules of XDH per fly. Large-scale fine-structure recombination experiments locate the genetic basis for this variation in the number of molecules of XDH per fly to a site immediately to the left of the XDH structural element within a region previously designated as the XDH control element. Moreover, experiments clearly separate this "underproducer" variant site from a previously described "overproducer" site within the control region. Examination of enzyme activity in electrophoretic gels of appropriate heterozygous genotypes demonstrates the cis-acting nature of this variation in the number of molecules of XDH. A revision of the map of the rosy locus, structural and control elements is presented in light of the additional mapping data now available. PMID:109351

  2. Confirmation of the 2p locus for the mild autosomal recessive lim-girdle muscular dystrophy gene (LGMD2B) in three families allows refinement of the candidate region

    SciTech Connect

    Bashir, R.; Iughetti, P.; Strachan, T.

    1995-05-01

    The mild autosomal recessive limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of muscle diseases. The first gene to be mapped and associated with this phenotype was a locus on 15q geographic isolate. These results have been confirmed in other populations, but it was shown that there is genetic heterogeneity for this form of LGMD. Recently, a second locus has been mapped to chromosome 2p. The confirmation of the mapping of this second locus in LGMD families from different populations is of utmost importance for the positional cloning of this gene (HGMW-approved symbol LGMD2B). In this publication, haplotypes generated from five chromosome 2 markers from all of the known large families linked to chromosome 2p are reported together with the recombinants that show the current most likely location of the LGMD 2B gene. 9 refs., 2 figs., 1 tab.

  3. A microsatellite linkage map of Drosophila mojavensis

    PubMed Central

    Staten, Regina; Schully, Sheri Dixon; Noor, Mohamed AF

    2004-01-01

    Background Drosophila mojavensis has been a model system for genetic studies of ecological adaptation and speciation. However, despite its use for over half a century, no linkage map has been produced for this species or its close relatives. Results We have developed and mapped 90 microsatellites in D. mojavensis, and we present a detailed recombinational linkage map of 34 of these microsatellites. A slight excess of repetitive sequence was observed on the X-chromosome relative to the autosomes, and the linkage groups have a greater recombinational length than the homologous D. melanogaster chromosome arms. We also confirmed the conservation of Muller's elements in 23 sequences between D. melanogaster and D. mojavensis. Conclusions The microsatellite primer sequences and localizations are presented here and made available to the public. This map will facilitate future quantitative trait locus mapping studies of phenotypes involved in adaptation or reproductive isolation using this species. PMID:15163351

  4. Multidimensional profiles of health locus of control in Hispanic Americans.

    PubMed

    Champagne, Brian R; Fox, Rina S; Mills, Sarah D; Sadler, Georgia Robins; Malcarne, Vanessa L

    2016-10-01

    Latent profile analysis identified health locus of control profiles among 436 Hispanic Americans who completed the Multidimensional Health Locus of Control scales. Results revealed four profiles: Internally Oriented-Weak, -Moderate, -Strong, and Externally Oriented. The profile groups were compared on sociocultural and demographic characteristics, health beliefs and behaviors, and physical and mental health outcomes. The Internally Oriented-Strong group had less cancer fatalism, religiosity, and equity health attributions, and more alcohol consumption than the other three groups; the Externally Oriented group had stronger equity health attributions and less alcohol consumption. Deriving multidimensional health locus of control profiles through latent profile analysis allows examination of the relationships of health locus of control subtypes to health variables.

  5. A highly polymorphic STR locus in Cannabis sativa.

    PubMed

    Hsieh, Hsing-Mei; Hou, Rur-Jyun; Tsai, Li-Chin; Wei, Chih-Sheng; Liu, Su-Wen; Huang, Li-Hung; Kuo, Yi-Chen; Linacre, Adrian; Lee, James Chun-I

    2003-01-01

    We report on the first short tandem repeat (STR) locus to be isolated from the plant Cannabis sativa. The STR locus, isolated by a hybrid-capture enrichment procedure, was found to contain a simple sequence repeat motif of 6 bp. This 6 bp repeat motif showed no variation in repeat length but with minor variations in repeat unit sequences. The data show the locus to be highly polymorphic with the number of repeat units ranging from 3 to 40 in 108 screened samples. The observed heterozygosity was approximately 87.04%. The forward and reverse primers (CS1F and CS1R) produced no PCR products in cross-reaction study from 20 species of plants, including highly related species such as Humulus japonicus and Nicotiana tabacum. This hexanucleotide repeat DNA locus could be used to identify cannabis samples and predict their genetic relationship as the test is specific to C. sativa and is highly reproducible.

  6. Recombinations in individuals homozygous by descent localize the Friedreich ataxia locus in a cloned 450-kb interval

    SciTech Connect

    Rodius, F.; Duclos, F.; Wrogemann, K.; Sirugo, G.; Mandel, J.L.; Koenig, M. ); Le Paslier, D.; Ougen, P.; Billault, A.; Cohen, D. )

    1994-06-01

    The locus for Friedreich ataxia (FRDA), a severe neurodegenerative disease, is tightly linked to markers D9S5 and D9S15, and analysis of rare recombination events has suggested the order cen-FRDA-D9S5-D9S15-qter. The authors report here the construction of a YAC contig extending 800 kb centromeric to D9S5t and the isolation of five new microsatellite markers from this region. In order to map these markers with respect to the FRDA locus, all within a 1-cM confidence interval, they sought to increase the genetic information of available FRDA families by considering homozygosity by descent and association with founder haplotypes in isolated populations. This approach allowed identification of one phase-known recombination and one probable historic recombination on haplotypes from Reunion Island patients, both of which place three of the five markers proximal to FRDA. This represents the first identification of close FRDA flanking markers on the centromeric side. The two other markers allowed narrowing of the breakpoint of a previously identified distal recombination that is >180 kb from D9S5 (26P). Taken together, the results place the FRDA locus in a 450-kb interval, which is small enough for direct search of candidate genes. A detailed rare cutter restriction map and a cosmid contig covering this interval were constructed and should facilitate the search of genes in this region. 26 refs., 3 figs., 2 tabs.

  7. The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters

    PubMed Central

    1988-01-01

    We have constructed a panel of Abelson murine leukemia virus- transformed pre-B cells to study the organization of the mouse VH gene families. Based on the analyses of VH gene deletions on 51 chromosomes with VH gene rearrangements, we have inferred a map order of the Igh locus that holds for both the Igha and Ighb haplotypes. We show that members of each VH gene family are generally clustered, although three family clusters (VHS107, VH36-60, VGAM3.8) are dispersed in two or three subregions of the locus. Members of two VH gene families, VHQ52 and VH7183, are extensively interspersed and map within the same subregion. An examination of the distribution of VH group members (VH II, I, and III) within the locus suggests that two major duplications may, in part, explain the dispersed pattern of VH family clusters. The relationship of VH organization and functional expression is discussed in terms of position-dependent and complexity-driven models. PMID:3199068

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

    SciTech Connect

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

    1994-01-15

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

  9. Neurolinguistic programming training, trait anxiety, and locus of control.

    PubMed

    Konefal, J; Duncan, R C; Reese, M A

    1992-06-01

    Training in the neurolinguistic programming techniques of shifting perceptual position, visual-kinesthetic dissociation, timelines, and change-history, all based on experiential cognitive processing of remembered events, leads to an increased awareness of behavioral contingencies and a more sensitive recognition of environmental cues which could serve to lower trait anxiety and increase the sense of internal control. This study reports on within-person and between-group changes in trait anxiety and locus of control as measured on the Spielberger State-Trait Anxiety Inventory and Wallston, Wallston, and DeVallis' Multiple Health Locus of Control immediately following a 21-day residential training in neurolinguistic programming. Significant with-in-person decreases in trait-anxiety scores and increases in internal locus of control scores were observed as predicted. Chance and powerful other locus of control scores were unchanged. Significant differences were noted on trait anxiety and locus of control scores between European and U.S. participants, although change scores were similar for the two groups. These findings are consistent with the hypothesis that this training may lower trait-anxiety scores and increase internal locus of control scores. A matched control group was not available, and follow-up was unfortunately not possible. PMID:1620774

  10. [Health locus of control of patients in disease management programmes].

    PubMed

    Schnee, M; Grikscheit, F

    2013-06-01

    Health locus of control beliefs plays a major role in improving self-management skills of the chronically ill - a main goal in disease management programmes (DMP). This study aims at characterising participants in disease management regarding their health locus of control. Data are based on 4 cross-sectional postal surveys between spring and autumn of 2006 and 2007 within the Health Care Monitor of the Bertelsmann Foundation. Among the 6 285 respondents, 1 266 are chronically ill and not enrolled in a DMP and 327 are participating in a DMP. A high internal locus of control (HLC) occurs significantly less often in DMP patients than in normal chronically ill patients (and healthy people) controlling for age, gender and social class. With increasing age, a high internal locus of control is also significantly less likely. When comparing healthy people, the chronically ill and the DMP participants a social gradient of a high internal locus of control belief can be observed. The weaker internal and higher doctor-related external locus of control of DMP participants should be carefully observed by the physician when trying to strengthen the patients' self-management skills. Evaluators of DMP should take into account the different baselines of DMP patients and relevant control groups and incorporate these differences into the evaluation.

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

    SciTech Connect

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

    1994-09-01

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

  12. RICH MAPS

    EPA Science Inventory

    Michael Goodchild recently gave eight reasons why traditional maps are limited as communication devices, and how interactive internet mapping can overcome these limitations. In the past, many authorities in cartography, from Jenks to Bertin, have emphasized the importance of sim...

  13. Map adventures

    USGS Publications Warehouse

    1994-01-01

    Map Adventures, with seven accompanying lessons, is appropriate for grades K-3. Students will learn basic concepts for visualizing objects from different perspectives and how to understand /and use maps.

  14. Historical Mapping

    USGS Publications Warehouse

    ,

    1999-01-01

    Maps become out of date over time. Maps that are out of date, however, can be useful to historians, attorneys, environmentalists, genealogists, and others interested in researching the background of a particular area. Local historians can compare a series of maps of the same area compiled over a long period of time to learn how the area developed. A succession of such maps can provide a vivid picture of how a place changed over time.

  15. On the Components of Segregation Distortion in Drosophila Melanogaster. IV. Construction and Analysis of Free Duplications for the Responder Locus

    PubMed Central

    Brittnacher, J. G.; Ganetzky, B.

    1989-01-01

    Male Drosophila heterozygous for an SD-bearing second chromosome and a normal homolog preferentially transmit the SD chromosome to their offspring. The distorted transmission involves the induced dysfunction of the sperm that receive the SD(+) chromosome. The loci on the SD chromosome responsible for causing distortion are the Sd locus the the E(SD) locus. Their target of action on the SD(+) chromosome is the Rsp(s) locus. Previous studies of Rsp(s) indicated that deletion of this locus rendered a chromosome insensitive to the action of SD and mapped Rsp(s) physically within the centric heterochromatin of 2R. In this study we have constructed a collection of marked free duplications for the centromeric region of a second chromosome that carried Rsp(s). The heterochromatic extent of each duplication as well as its sensitivity to distortion was determined. We found that Rsp(s) is the most proximal known locus within the 2R heterochromatin. Furthermore, our results demonstrate that the presence of Rsp(s) is not only necessary but sufficient to confer sensitivity to distortion irrespective of its association with an intact second chromosome or one that pairs meiotically with an SD chromosome. By use of these duplications we increased the usual dosage of Rsp(s) relative to SD to determine whether there was any competition for limited amounts of SD [and/or E(SD)] product. When two Rsp(s)-bearing chromosomes are present within the same spermatocyte nucleus an SD chromosome is capable of causing efficient distortion of both. However, at least in some cases the degree of distortion against a given Rsp(s) was reduced by the presence of an extra dose of Rsp(s) indicating that there was some competition between them. The bearing of these results on present models of segregation distortion are discussed. PMID:2498160

  16. A survey of EMS-induced biennial Beta vulgaris mutants reveals a novel bolting locus which is unlinked to the bolting gene B.

    PubMed

    Büttner, Bianca; Abou-Elwafa, Salah F; Zhang, Wenying; Jung, Christian; Müller, Andreas E

    2010-10-01

    Beta vulgaris is a facultative perennial species which exhibits large intraspecific variation in vernalization requirement and includes cultivated biennial forms such as the sugar beet. Vernalization requirement is under the genetic control of the bolting locus B on chromosome II. Previously, ethyl methanesulfonate (EMS) mutagenesis of an annual accession had yielded several mutants which require vernalization to bolt and behave as biennials. Here, five F2 populations derived from crosses between biennial mutants and annual beets were tested for co-segregation of bolting phenotypes with genotypic markers located at the B locus. One mutant appears to be mutated at the B locus, suggesting that an EMS-induced mutation of B can be sufficient to abolish annual bolting. Co-segregation analysis in four populations indicates that the genetic control of bolting also involves previously unknown major loci not linked to B, one of which also affects bolting time and was genetically mapped to chromosome IX.

  17. Molecular mapping of chromosomes 17 and X

    SciTech Connect

    Barker, D.F.

    1989-01-01

    The basic aims of this project are the construction of high density genetic maps of chromosomes 17 and X and the utilization of these maps for the subsequent isolation of a set of physically overlapping DNA segment clones. The strategy depends on the utilization of chromosome specific libraries of small (1--15 kb) segments from each of the two chromosomes. Since the time of submission of our previous progress report, we have refined the genetic map of markers which we had previously isolated for chromosome 17. We have completed our genetic mapping in CEPH reference and NF1 families of 15 markers in the pericentric region of chromosome 17. Physical mapping results with three probes, were shown be in very close genetic proximity to the NF1 gene, with respect to two translocation breakpoints which disrupt the activity of the gene. All three of the probes were found to lie between the centromere and the most proximal translocation breakpoint, providing important genetic markers proximal to the NF1 gene. Our primary focus has shifted to the X chromosome. We have isolated an additional 30 polymorphic markers, bringing the total number we have isolated to over 80. We have invested substantial effort in characterizing the polymorphisms at each of these loci and constructed plasmid subclones which reveal the polymorphisms for nearly all of the loci. These subclones are of practical value in that they produce simpler and stronger patterns on human genomic Southern blots, thus improving the efficiency of the genetic mapping experiments. These subclones may also be of value for deriving DNA sequence information at each locus, necessary for establishing polymerase chain reaction primers specific for each locus. Such information would allow the use of each locus as a sequence tagged site.

  18. Mapping-by-sequencing in complex polyploid genomes using genic sequence capture: a case study to map yellow rust resistance in hexaploid wheat.

    PubMed

    Gardiner, Laura-Jayne; Bansept-Basler, Pauline; Olohan, Lisa; Joynson, Ryan; Brenchley, Rachel; Hall, Neil; O'Sullivan, Donal M; Hall, Anthony

    2016-08-01

    Previously we extended the utility of mapping-by-sequencing by combining it with sequence capture and mapping sequence data to pseudo-chromosomes that were organized using wheat-Brachypodium synteny. This, with a bespoke haplotyping algorithm, enabled us to map the flowering time locus in the diploid wheat Triticum monococcum L. identifying a set of deleted genes (Gardiner et al., 2014). Here, we develop this combination of gene enrichment and sliding window mapping-by-synteny analysis to map the Yr6 locus for yellow stripe rust resistance in hexaploid wheat. A 110 MB NimbleGen capture probe set was used to enrich and sequence a doubled haploid mapping population of hexaploid wheat derived from an Avalon and Cadenza cross. The Yr6 locus was identified by mapping to the POPSEQ chromosomal pseudomolecules using a bespoke pipeline and algorithm (Chapman et al., 2015). Furthermore the same locus was identified using newly developed pseudo-chromosome sequences as a mapping reference that are based on the genic sequence used for sequence enrichment. The pseudo-chromosomes allow us to demonstrate the application of mapping-by-sequencing to even poorly defined polyploidy genomes where chromosomes are incomplete and sub-genome assemblies are collapsed. This analysis uniquely enabled us to: compare wheat genome annotations; identify the Yr6 locus - defining a smaller genic region than was previously possible; associate the interval with one wheat sub-genome and increase the density of SNP markers associated. Finally, we built the pipeline in iPlant, making it a user-friendly community resource for phenotype mapping. PMID:27144898

  19. Evaluating the Results of Genomewide Linkage Scans of Complex Traits by Locus Counting

    PubMed Central

    Wiltshire, Steven; Cardon, Lon R.; McCarthy, Mark I.

    2002-01-01

    The evaluation of results from primary genomewide linkage scans of complex human traits remains an area of importance and considerable debate. Apart from the usual assessment of statistical significance by use of asymptotic and empirical calculations, an additional means of evaluation—based on counting the number of distinct regions showing evidence of linkage—is possible. We have explored the characteristics of such a locus-counting method over a range of experimental conditions typically encountered during genomewide scans for complex trait loci. Under the null hypothesis, factors that have an impact on the informativeness of the data—such as map density, availability of parental data, and completeness of genotyping—are seen to markedly influence the number of regions of excess allele sharing and the empirically derived genomewide significance of the associated LOD score thresholds. In some circumstances, the expected number of regions is less than one-quarter of that predicted under the assumption of a dense map and complete extraction of inheritance information. We have applied this method to a previously analyzed data set—the Warren 2 genome scan for type 2–diabetes susceptibility—and demonstrate that more regions showing evidence for linkage were observed in the primary genome scan than would be expected by chance, across the whole range of LOD scores, even though no single linkage result achieved empirical genomewide statistical significance. Locus counting may be useful in assessing the results from genome scans for complex traits in general, especially because relatively few scans generate evidence for linkage reaching genomewide significance by dense-map criteria. By taking account of the effects of reduced data informativeness on the expected number of regions showing evidence for linkage, a more meaningful, and less conservative, evaluation of the results from such linkage studies is possible. PMID:12355401

  20. Towards cloning the WAS-gene locus: YAC-contigs and PFGE analysis

    SciTech Connect

    Meindi, A.; Schindelhauer, D.; Hellebrand, H.

    1994-09-01

    Patients with X-linked recessive Wiskott-Aldrich syndrome (WAS) manifest eczema, thrombocytopenia and severe immunodeficiency. Mapping studies place the WAS gene locus between the markers TIMP and DXS255 which both have been shown to be recombinant with the disease locus. Linkage analysis in eight families including a large Swiss family showed tight linkage of the disease to the loci DXS255 and DXS1126 and exclusion of TIMP as well as polymorphic loci adjacent to the OATL1 pseudogene cluster (e.g., DXS6616). Physical mapping with established YAC contigs and a radiation hybrid encompassing the Xp11.22-11.3 region revealed the loci order TIMP-PFC-elk1-DXS1367-DXS6616-OATL1-(DXS11260DXS226)-C5-3-TGE-3, SYP and (DXS255-DXS146). The markers TIMP and C5-3 are contained on the same 1.6 Mb MluI-fragment. A novel expressed sequence (R1) could be placed between elk-1 and the PFC gene while the STS C5-3 could be localized adjacent to DXS1126. The gene cluster around DXS1126 could be connected with the TFE-3 and synaptophysin genes which map on the same 400 kb MluI fragment and two overlapping YACs. The minimum distance between SYP and DXS255 is 1.2 Mb; the maximum distance is 2.2 Mb. Expressed sequences which are obtained from a cosmid contig around DXS1126 and C5-3 are being used for mutation screening in WAS patients.

  1. A conserved supergene locus controls colour pattern diversity in Heliconius butterflies.

    PubMed

    Joron, Mathieu; Papa, Riccardo; Beltrán, Margarita; Chamberlain, Nicola; Mavárez, Jesús; Baxter, Simon; Abanto, Moisés; Bermingham, Eldredge; Humphray, Sean J; Rogers, Jane; Beasley, Helen; Barlow, Karen; ffrench-Constant, Richard H; Mallet, James; McMillan, W Owen; Jiggins, Chris D

    2006-10-01

    We studied whether similar developmental genetic mechanisms are involved in both convergent and divergent evolution. Mimetic insects are known for their diversity of patterns as well as their remarkable evolutionary convergence, and they have played an important role in controversies over the respective roles of selection and constraints in adaptive evolution. Here we contrast three butterfly species, all classic examples of Müllerian mimicry. We used a genetic linkage map to show that a locus, Yb, which controls the presence of a yellow band in geographic races of Heliconius melpomene, maps precisely to the same location as the locus Cr, which has very similar phenotypic effects in its co-mimic H. erato. Furthermore, the same genomic location acts as a "supergene", determining multiple sympatric morphs in a third species, H. numata. H. numata is a species with a very different phenotypic appearance, whose many forms mimic different unrelated ithomiine butterflies in the genus Melinaea. Other unlinked colour pattern loci map to a homologous linkage group in the co-mimics H. melpomene and H. erato, but they are not involved in mimetic polymorphism in H. numata. Hence, a single region from the multilocus colour pattern architecture of H. melpomene and H. erato appears to have gained control of the entire wing-pattern variability in H. numata, presumably as a result of selection for mimetic "supergene" polymorphism without intermediates. Although we cannot at this stage confirm the homology of the loci segregating in the three species, our results imply that a conserved yet relatively unconstrained mechanism underlying pattern switching can affect mimicry in radically different ways. We also show that adaptive evolution, both convergent and diversifying, can occur by the repeated involvement of the same genomic regions.

  2. Narrowing down the apricot Plum pox virus resistance locus and comparative analysis with the peach genome syntenic region.

    PubMed

    Vera Ruiz, Elsa María; Soriano, José Miguel; Romero, Carlos; Zhebentyayeva, Tetyana; Terol, Javier; Zuriaga, Elena; Llácer, Gerardo; Abbott, Albert Glenn; Badenes, María Luisa

    2011-08-01

    Sharka disease, caused by the Plum pox virus (PPV), is one of the main limiting factors for stone fruit crops worldwide. Only a few resistance sources have been found in apricot (Prunus armeniaca L.), and most studies have located a major PPV resistance locus (PPVres) on linkage group 1 (LG1). However, the mapping accuracy was not sufficiently reliable and PPVres was predicted within a low confidence interval. In this study, we have constructed two high-density simple sequence repeat (SSR) improved maps with 0.70 and 0.68 markers/cm, corresponding to LG1 of 'Lito' and 'Goldrich' PPV-resistant cultivars, respectively. Using these maps, and excluding genotype-phenotype incongruent individuals, a new binary trait locus (BTL) analysis for PPV resistance was performed, narrowing down the PPVres support intervals to 7.3 and 5.9 cm in 'Lito' and 'Goldrich', respectively. Subsequently, 71 overlapping oligonucleotides (overgo) probes were hybridized against an apricot bacterial artificial chromosome (BAC) library, identifying 870 single BACs from which 340 were anchored onto a map region of approximately 30-40 cm encompassing PPVres. Partial BAC contigs assigned to the two allelic haplotypes (resistant/susceptible) of the PPVres locus were built by high-information content fingerprinting (HICF). In addition, a total of 300 BAC-derived sequences were obtained, and 257 showed significant homology with the peach genome scaffold_1 corresponding to LG1. According to the peach syntenic genome sequence, PPVres was predicted within a region of 2.16 Mb in which a few candidate resistance genes were identified.

  3. A copy number variant at the KITLG locus likely confers risk for canine squamous cell carcinoma of the digit.

    PubMed

    Karyadi, Danielle M; Karlins, Eric; Decker, Brennan; vonHoldt, Bridgett M; Carpintero-Ramirez, Gretchen; Parker, Heidi G; Wayne, Robert K; Ostrander, Elaine A

    2013-03-01

    The domestic dog is a robust model for studying the genetics of complex disease susceptibility. The strategies used to develop and propagate modern breeds have resulted in an elevated risk for specific diseases in particular breeds. One example is that of Standard Poodles (STPOs), who have increased risk for squamous cell carcinoma of the digit (SCCD), a locally aggressive cancer that causes lytic bone lesions, sometimes with multiple toe recurrence. However, only STPOs of dark coat color are at high risk; light colored STPOs are almost entirely unaffected, suggesting that interactions between multiple pathways are necessary for oncogenesis. We performed a genome-wide association study (GWAS) on STPOs, comparing 31 SCCD cases to 34 unrelated black STPO controls. The peak SNP on canine chromosome 15 was statistically significant at the genome-wide level (P(raw) = 1.60 × 10(-7); P(genome) = 0.0066). Additional mapping resolved the region to the KIT Ligand (KITLG) locus. Comparison of STPO cases to other at-risk breeds narrowed the locus to a 144.9-Kb region. Haplotype mapping among 84 STPO cases identified a minimal region of 28.3 Kb. A copy number variant (CNV) containing predicted enhancer elements was found to be strongly associated with SCCD in STPOs (P = 1.72 × 10(-8)). Light colored STPOs carry the CNV risk alleles at the same frequency as black STPOs, but are not susceptible to SCCD. A GWAS comparing 24 black and 24 light colored STPOs highlighted only the MC1R locus as significantly different between the two datasets, suggesting that a compensatory mutation within the MC1R locus likely protects light colored STPOs from disease. Our findings highlight a role for KITLG in SCCD susceptibility, as well as demonstrate that interactions between the KITLG and MC1R loci are potentially required for SCCD oncogenesis. These findings highlight how studies of breed-limited diseases are useful for disentangling multigene disorders.

  4. Identification of the modifier locus that suppresses neonatal lethality in (♀DDD × ♂DH- Dh/+) F₁-Dh/+ male mice.

    PubMed

    Suto, Jun-ichi

    2011-10-01

    Most F(1)-Dh/+ male mice resulting from a cross between inbred DDD strain females and DH-Dh/+ strain males exhibit growth retardation and die during the neonatal period. The lethality is caused by a combination of three independent gene loci, namely the Dh locus on chromosome 1, Grdhq1 locus on the X chromosome, and a putative Y chromosome-linked locus in some strains. Among these loci, Grdhq1 was previously mapped to a distal region of the X chromosome using progeny from♀(♀DDD × ♂DH-+/+) F(1) × ♂DH-Dh/+ mice. In this study, fine mapping of Grdhq1 was performed using progeny of ♀(♀DDD × ♂CAST/EiJ) F(1) ♂DH-Dh/+ mice. Contrary to expectation, Dh/+ male pups carrying the DDD allele at DXMit135 (genetic marker nearest to Grdhq1) survived to weaning. The presence of modifier loci that suppressed the lethality by impeding the action of Grdhq1 was suggested; therefore, a genome-wide scan was performed in the surviving Dh/+ males. As a result, a significant modifier locus was identified on proximal chromosome 11. This in turn suggested that Grdhq1 was located more distally than we had expected; that is, the actual location of Grdhq1 appeared to be near and/or distal to the Mid1 locus. Thus, the results revealed that the neonatal lethality in (DDD × DH-Dh/+) F(1)-Dh/+ males was caused by the fourth gene locus on chromosome 11 in addition to the above-mentioned three gene loci on chromosomes 1, X, and Y.

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

    PubMed

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

    2010-10-01

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

  6. Topographic mapping

    USGS Publications Warehouse

    ,

    2008-01-01

    The U.S. Geological Survey (USGS) produced its first topographic map in 1879, the same year it was established. Today, more than 100 years and millions of map copies later, topographic mapping is still a central activity for the USGS. The topographic map remains an indispensable tool for government, science, industry, and leisure. Much has changed since early topographers traveled the unsettled West and carefully plotted the first USGS maps by hand. Advances in survey techniques, instrumentation, and design and printing technologies, as well as the use of aerial photography and satellite data, have dramatically improved mapping coverage, accuracy, and efficiency. Yet cartography, the art and science of mapping, may never before have undergone change more profound than today.

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

    PubMed Central

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

    2016-01-01

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

  8. Age and sex based genetic locus heterogeneity in type 1 diabetes

    PubMed Central

    Paterson, A.; Petronis, A.

    2000-01-01

    BACKGROUND—Two genome scans for susceptibility loci for type 1 diabetes using large collections of families have recently been reported. Apart from strong linkage in both studies of the HLA region on chromosome 6p, clear consistent evidence for linkage was not observed at any other loci. One possible explanation for this is a high degree of locus heterogeneity in type 1 diabetes, and we hypothesised that the sex of affected offspring, age of diagnosis, and parental origin of shared alleles may be the bases of heterogeneity at some loci.
METHODS—Using data from a genome wide linkage study of 356 affected sib pairs with type 1 diabetes, we performed linkage analyses using parental origin of shared alleles in subgroups based on (1) sex of affected sibs and (2) age of diagnosis.
RESULTS—Among the results obtained, we observed that evidence for linkage to IDDM4 on chromosome 11q13 occurred predominantly from opposite sex, rather than same sex sib pairs. At a locus on chromosome 4q, evidence for linkage was observed in sibs where one was diagnosed above the age of 10 years and the other diagnosed below 10 years of age.
CONCLUSIONS—We show that heterogeneity tests based on age of diagnosis, sex of affected subject, and parental origin of shared alleles may be helpful in reducing locus heterogeneity in type 1 diabetes. If repeated in other samples, these findings may assist in the mapping of susceptibility loci for type 1 diabetes. Similar analyses can be recommended in other complex diseases.


Keywords: type 1 diabetes; age of diagnosis; sex; parental origin of alleles PMID:10699054

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    1990-01-01

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

  11. Comparative sequence analysis of the potato cyst nematode resistance locus H1 reveals a major lack of co-linearity between three haplotypes in potato (Solanum tuberosum ssp.).

    PubMed

    Finkers-Tomczak, Anna; Bakker, Erin; de Boer, Jan; van der Vossen, Edwin; Achenbach, Ute; Golas, Tomasz; Suryaningrat, Suwardi; Smant, Geert; Bakker, Jaap; Goverse, Aska

    2011-02-01

    The H1 locus confers resistance to the potato cyst nematode Globodera rostochiensis pathotypes 1 and 4. It is positioned at the distal end of chromosome V of the diploid Solanum tuberosum genotype SH83-92-488 (SH) on an introgression segment derived from S. tuberosum ssp. andigena. Markers from a high-resolution genetic map of the H1 locus (Bakker et al. in Theor Appl Genet 109:146-152, 2004) were used to screen a BAC library to construct a physical map covering a 341-kb region of the resistant haplotype coming from SH. For comparison, physical maps were also generated of the two haplotypes from the diploid susceptible genotype RH89-039-16 (S. tuberosum ssp. tuberosum/S. phureja), spanning syntenic regions of 700 and 319 kb. Gene predictions on the genomic segments resulted in the identification of a large cluster consisting of variable numbers of the CC-NB-LRR type of R genes for each haplotype. Furthermore, the regions were interspersed with numerous transposable elements and genes coding for an extensin-like protein and an amino acid transporter. Comparative analysis revealed a major lack of gene order conservation in the sequences of the three closely related haplotypes. Our data provide insight in the evolutionary mechanisms shaping the H1 locus and will facilitate the map-based cloning of the H1 resistance gene.

  12. Genetic and Quantitative Trait Locus Analysis for Bio-Oil Compounds after Fast Pyrolysis in Maize Cobs.

    PubMed

    Jeffrey, Brandon; Kuzhiyil, Najeeb; de Leon, Natalia; Lübberstedt, Thomas

    2016-01-01

    Fast pyrolysis has been identified as one of the biorenewable conversion platforms that could be a part of an alternative energy future, but it has not yet received the same attention as cellulosic ethanol in the analysis of genetic inheritance within potential feedstocks such as maize. Ten bio-oil compounds were measured via pyrolysis/gas chromatography-mass spectrometry (Py/GC-MS) in maize cobs. 184 recombinant inbred lines (RILs) of the intermated B73 x Mo17 (IBM) Syn4 population were analyzed in two environments, using 1339 markers, for quantitative trait locus (QTL) mapping. QTL mapping was performed using composite interval mapping with significance thresholds established by 1000 permutations at α = 0.05. 50 QTL were found in total across those ten traits with R2 values ranging from 1.7 to 5.8%, indicating a complex quantitative inheritance of these traits. PMID:26745365

  13. Genetic and Quantitative Trait Locus Analysis for Bio-Oil Compounds after Fast Pyrolysis in Maize Cobs.

    PubMed

    Jeffrey, Brandon; Kuzhiyil, Najeeb; de Leon, Natalia; Lübberstedt, Thomas

    2016-01-01

    Fast pyrolysis has been identified as one of the biorenewable conversion platforms that could be a part of an alternative energy future, but it has not yet received the same attention as cellulosic ethanol in the analysis of genetic inheritance within potential feedstocks such as maize. Ten bio-oil compounds were measured via pyrolysis/gas chromatography-mass spectrometry (Py/GC-MS) in maize cobs. 184 recombinant inbred lines (RILs) of the intermated B73 x Mo17 (IBM) Syn4 population were analyzed in two environments, using 1339 markers, for quantitative trait locus (QTL) mapping. QTL mapping was performed using composite interval mapping with significance thresholds established by 1000 permutations at α = 0.05. 50 QTL were found in total across those ten traits with R2 values ranging from 1.7 to 5.8%, indicating a complex quantitative inheritance of these traits.

  14. Genetic and Quantitative Trait Locus Analysis for Bio-Oil Compounds after Fast Pyrolysis in Maize Cobs

    PubMed Central

    Jeffrey, Brandon; Kuzhiyil, Najeeb; de Leon, Natalia; Lübberstedt, Thomas

    2016-01-01

    Fast pyrolysis has been identified as one of the biorenewable conversion platforms that could be a part of an alternative energy future, but it has not yet received the same attention as cellulosic ethanol in the analysis of genetic inheritance within potential feedstocks such as maize. Ten bio-oil compounds were measured via pyrolysis/gas chromatography-mass spectrometry (Py/GC-MS) in maize cobs. 184 recombinant inbred lines (RILs) of the intermated B73 x Mo17 (IBM) Syn4 population were analyzed in two environments, using 1339 markers, for quantitative trait locus (QTL) mapping. QTL mapping was performed using composite interval mapping with significance thresholds established by 1000 permutations at α = 0.05. 50 QTL were found in total across those ten traits with R2 values ranging from 1.7 to 5.8%, indicating a complex quantitative inheritance of these traits. PMID:26745365

  15. Locus equations are an acoustic expression of articulator synergy

    PubMed Central

    Iskarous, Khalil; Fowler, Carol A.; Whalen, D. H.

    2010-01-01

    The study investigated the articulatory basis of locus equations, regression lines relating F2 at the start of a Consonant-Vowel (CV) transition to F2 at the middle of the vowel, with C fixed and V varying. Several studies have shown that consonants of different places of articulation have locus equation slopes that descend from labial to velar to alveolar, and intercept magnitudes that increase in the opposite order. Using formulas from the theory of bivariate regression that express regression slopes and intercepts in terms of standard deviations and averages of the variables, it is shown that the slope directly encodes a well-established measure of coarticulation resistance. It is also shown that intercepts are directly related to the degree to which the tongue body assists the formation of the constriction for the consonant. Moreover, it is shown that the linearity of locus equations and the linear relation between locus equation slopes and intercepts originates in linearity in articulation between the horizontal position of the tongue dorsum in the consonant and to that in the vowel. It is concluded that slopes and intercepts of acoustic locus equations are measures of articulator synergy. PMID:20968373

  16. Identification of the BrRHP1 locus that confers resistance to downy mildew in Chinese cabbage (Brassica rapa ssp. pekinensis) and development of linked molecular markers.

    PubMed

    Kim, Sunggil; Song, Young Ha; Lee, Ji-Yeon; Choi, Su Ryun; Dhandapani, Vignesh; Jang, Chang Soon; Lim, Yong Pyo; Han, Taeho

    2011-11-01

    Inheritance of resistance to downy mildew (Hyaloperonospora parasitica) in Chinese cabbage (Brassica rapa ssp. pekinensis) was studied using inbred parental lines RS1 and SS1 that display strong resistance and severe susceptibility, respectively. F(1), F(2), and BC(1)F(1) populations were evaluated for their responses to downy mildew infection. Resistance to downy mildew was conditioned by a single dominant locus designated BrRHP1. A random amplified polymorphic DNA (RAPD) marker linked to BrRHP1 was identified using bulked segregant analysis and two molecular markers designated BrPERK15A and BrPERK15B were developed. BrPERK15B was polymorphic between the parental lines used to construct the reference linkage map of B. rapa, allowing the mapping of the BrRHP1 locus to the A1 linkage group. Using bacterial artificial chromosome clone sequences anchored to the A1 linkage group, six simple polymerase chain reaction (PCR) markers were developed for use in marker-assisted breeding of downy mildew resistance in Chinese cabbage. Four simple PCR markers flanking the BrRHP1 locus were shown to be collinear with the long-arm region of Arabidopsis chromosome 3. The two closely linked flanking markers delimit the BrRHP1 locus within a 2.2-Mb interval of this Arabidopsis syntenic region.

  17. Identificaiton of a clubroot resistance locus conferring resistance to a Plasmodiophora brassicae classified into pathotype group 3 in Chinese cabbage (Brassica rapa L.).

    PubMed

    Kato, Takeyuki; Hatakeyama, Katsunori; Fukino, Nobuko; Matsumoto, Satoru

    2012-09-01

    In Chinese cabbage (Brassica rapa), the clubroot resistance (CR) genes Crr1 and Crr2 are effective against the mild Plasmodiophora brassicae isolate Ano-01 and the more virulent isolate Wakayama-01, but not against isolate No. 14, classified into pathotype group 3. 'Akiriso', a clubroot-resistant F(1) cultivar, showed resistance to isolate No. 14. To increase the durability of resistance, we attempted to identify the CR locus in 'Akiriso'. CR in 'Akiriso' segregated as a single dominant gene and was linked to several molecular markers that were also linked to CRb, a CR locus from cultivar 'CR Shinki'. We developed additional markers around CRb and constructed partial genetic maps of this region in 'Akiriso' and 'CR Shinki'. The positions and order of markers in the genetic maps of the two cultivars were very similar. The segregation ratios for resistance to isolate No. 14 in F(2) populations derived from each of the two cultivars were also very similar. These results suggest that the CR locus in 'Akiriso' is CRb or a tightly linked locus. The newly developed markers in this study were more closely linked to CRb than previously reported markers and will be useful for marker-assisted selection of CRb in Chinese cabbage breeding.

  18. Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus

    PubMed Central

    Min-Oo, Gundula; Fortin, Anny; Pitari, Giuseppina; Tam, Mifong; Stevenson, Mary M.; Gros, Philippe

    2007-01-01

    Mouse strains AcB55 and AcB61 are resistant to malaria by virtue of a mutation in erythrocyte pyruvate kinase (PklrI90N). Linkage analysis in [AcB55 × A/J] F2 mice detected a second locus (Char9; logarithm of odds = 4.74) that regulates the blood-stage replication of Plasmodium chabaudi AS independently of Pklr. We characterized the 77 genes of the Char9 locus for tissue-specific expression, strain-specific alterations in gene expression, and polymorphic variants that are possibly associated with differential susceptibility. We identified Vnn1/Vnn3 as the likely candidates responsible for Char9. Vnn3/Vnn1 map within a conserved haplotype block and show expression levels that are strictly cis-regulated by this haplotype. The absence of Vnn messenger RNA expression and lack of pantetheinase protein activity in tissues are associated with susceptibility to malaria and are linked to a complex rearrangement in the Vnn3 promoter region. The A/J strain also carries a unique nonsense mutation that leads to a truncated protein. Vanin genes code for a pantetheinase involved in the production of cysteamine, a key regulator of host responses to inflammatory stimuli. Administration of cystamine in vivo partially corrects susceptibility to malaria in A/J mice, as measured by reduced blood parasitemia and decreased mortality. These studies suggest that pantetheinase is critical for the host response to malaria. PMID:17312006

  19. Genetic Control Of Natural Killing and In Vivo Tumor Elimination by the Chok Locus

    PubMed Central

    Idris, Azza H.; Iizuka, Koho; Smith, Hamish R.C.; Scalzo, Anthony A.; Yokoyama, Wayne M.

    1998-01-01

    The molecular mechanisms underlying target recognition during natural killing are not well understood. One approach to dissect the complexities of natural killer (NK) cell recognition is through exploitation of genetic differences among inbred mouse strains. In this study, we determined that interleukin 2–activated BALB/c-derived NK cells could not lyse Chinese hamster ovary (CHO) cells as efficiently as C57BL/6-derived NK cells, despite equivalent capacity to kill other targets. This strain-determined difference was also exhibited by freshly isolated NK cells, and was determined to be independent of host major histocompatibility haplotype. Furthermore, CHO killing did not correlate with expression of NK1.1 or 2B4 activation molecules. Genetic mapping studies revealed linkage between the locus influencing CHO killing, termed Chok, and loci encoded within the NK gene complex (NKC), suggesting that Chok encodes an NK cell receptor specific for CHO cells. In vivo assays recapitulated the in vitro data, and both studies determined that Chok regulates an NK perforin–dependent cytotoxic process. These results may have implications for the role of NK cells in xenograft rejection. Our genetic analysis suggests Chok is a single locus that affects NK cell–mediated cytotoxicity similar to other NKC loci that also regulate the complex activity of NK cells. PMID:9858511

  20. Structural forms of the human amylase locus and their relationships to SNPs, haplotypes, and obesity

    PubMed Central

    Usher, Christina L; Handsaker, Robert E; Esko, Tõnu; Tuke, Marcus A; Weedon, Michael N; Hastie, Alex R; Cao, Han; Moon, Jennifer E; Kashin, Seva; Fuchsberger, Christian; Metspalu, Andres; Pato, Carlos N; Pato, Michele T; McCarthy, Mark I; Boehnke, Michael; Altshuler, David M; Frayling, Timothy M; Hirschhorn, Joel N; McCarroll, Steven A

    2016-01-01

    Hundreds of genes reside in structurally complex, poorly understood regions of the human genome1-3. One such region contains the three amylase genes (AMY2B, AMY2A, and AMY1) responsible for digesting starch into sugar. The copy number of AMY1 is reported to be the genome’s largest influence on obesity4, though genome-wide association studies for obesity have found this locus unremarkable. Using whole genome sequence analysis3,5, droplet digital PCR6, and genome mapping7, we identified eight common structural haplotypes of the amylase locus that suggest its mutational history. We found that AMY1 copy number in individuals’ genomes is generally even (rather than odd) and partially correlates to nearby SNPs, which do not associate with BMI. We measured amylase gene copy number in 1,000 obese or lean Estonians and in two other cohorts totaling ~3,500 individuals. We had 99% power to detect the lower bound of the reported effects on BMI4, yet found no association. PMID:26098870

  1. Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer

    PubMed Central

    O’Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica MJ; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

    2015-01-01

    Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3,633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6,607 EC cases and 37,925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P = 1.86 × 10−5), which was stronger for cancers of endometrioid subtype (P = 3.76 × 10−6). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types. PMID:26330482

  2. Lrmp and Bcat1 are candidates for the type I diabetes susceptibility locus Idd6.

    PubMed

    Grimm, Christina H; Rogner, Ute C; Avner, Philip

    2003-06-01

    Three type 1 diabetes associated regions on distal mouse chromosome 6 have recently been defined by the construction and analysis of a series of congenic strains, carrying C3H/HeJ genomic material on a NOD/Lt genetic background. Whilst NOD/Lt alleles at the most distal locus Idd6 confer susceptibility, C3H/HeJ alleles confer resistance to diabetes. Idd6 overlaps with a locus controlling low rates of proliferation in immature NOD-thymocytes, suggesting that Idd6 could be controlling diabetes development through an effect on T cell proliferation rates. Candidates for Idd6 therefore include genes, which are implicated in the immune system and/or in the control of cell proliferation rates, such as Lrmp (Jaw1), Bcat1 and Kras2 that map to the Idd6 candidate region. In the present study, we have undertaken an expression and mutational analysis of all three genes. A surprisingly large number of polymorphisms and amino acid changes were identified in both Lrmp and Bcat1 indicating that they are candidates for Idd6. The two genes are located within a genomic interval of about 3 Mb that contains a large number of single nucleotide polymorphisms (SNP) and which has possibly been derived from distinct ancestral haplotypes in the C3H/HeJ and NOD/Lt strains.

  3. Identification of AFLP and STS markers closely linked to the def locus in pea.

    PubMed

    von Stackelberg, M; Lindemann, S; Menke, M; Riesselmann, S; Jacobsen, H-J

    2003-05-01

    The recessive mutation of the def gene of pea (Pisum sativum L.) leads to the loss of the hilum, the abscission zone between the seed and the pod. Thereby, it reduces the free dispersal of the seeds through pod shattering. As a prerequisite for a gene isolation via a map-based cloning approach, bulked segregant analysis followed by single plant analyses of over 200 homozygous individuals of a population of 476 F2 plants derived from a cross between 'DGV' (def wild-type) and 'PF' (def mutant), were used to detect markers closely linked to the def locus. The AFLP technique in combination with silver staining was used to maximize numbers of reproducible marker loci. Fifteen AFLP loci showed a genetic distance less than 5 and two of them less than 1 centiMorgans (cM) to the gene of interest. AFLPs were converted into sequence tagged sites (STSs) and into a newly refined AFLP-based single locus marker named the 'sequence specified AFLP' (ssAFLP).

  4. In Vitro Whole-Genome Analysis Identifies a Susceptibility Locus for HIV-1

    PubMed Central

    Ciuffi, Angela; Robyr, Daniel; Taffé, Patrick; Muñoz, Miguel; Beckmann, Jacques S; Antonarakis, Stylianos E; Telenti, Amalio

    2008-01-01

    Advances in large-scale analysis of human genomic variability provide unprecedented opportunities to study the genetic basis of susceptibility to infectious agents. We report here the use of an in vitro system for the identification of a locus on HSA8q24.3 associated with cellular susceptibility to HIV-1. This locus was mapped through quantitative linkage analysis using cell lines from multigeneration families, validated in vitro, and followed up by two independent association studies in HIV-positive individuals. Single nucleotide polymorphism rs2572886, which is associated with cellular susceptibility to HIV-1 in lymphoblastoid B cells and in primary T cells, was also associated with accelerated disease progression in one of two cohorts of HIV-1–infected patients. Biological analysis suggests a role of the rs2572886 region in the regulation of the LY6 family of glycosyl-phosphatidyl-inositol (GPI)–anchored proteins. Genetic analysis of in vitro cellular phenotypes provides an attractive approach for the discovery of susceptibility loci to infectious agents. PMID:18288889

  5. Identification and characterization of the non-PTS fru locus of Bacillus megaterium ATCC 14581.

    PubMed

    Chiou, C-Y; Wang, H-H; Shaw, G-C

    2002-10-01

    A genetic locus that is adjacent to the gene encoding the small acid-soluble protein SASP C-4 of Bacillus megaterium has been identified. This locus, designated fru, contains a beta-fructosidase gene (fruA), a gene encoding a hydrophobic protein that is closely related to non-PTS sugar permeases of the proton symport type (fruP), and a gene coding for a transcriptional regulator of the LacI/GalR family (fruR). The FruA protein can hydrolyze sucrose and raffinose, but not maltose, isomaltose, trehalose, melibiose or lactose. The transcription initiation site of fruP has been mapped and the fruP promoter identified. Gel mobility shift assays showed that the FruR protein can bind specifically to a DNA fragment containing the fruP promoter region. DNase I footprinting analysis has defined the FruR binding site. Disruption of fruR led to high-level constitutive expression of fruPA, but had no effect on expression from the fruR promoter itself, indicating that FruR acts as a repressor of fruPA expression, but does not autoregulate its own synthesis. Interestingly, expression of fruPA in B. megaterium was not induced by sucrose, raffinose, fructose or inulin, whereas the constitutive expression of fruPA in a fruR mutant was repressed by both glucose and sucrose. Possible physiological implications of these findings are discussed. PMID:12395198

  6. DNA Adenine Methylase Mutants of Salmonella Typhimurium and a Novel Dam-Regulated Locus

    PubMed Central

    Torreblanca, J.; Casadesus, J.

    1996-01-01

    Mutants of Salmonella typhimurium lacking DNA adenine methylase were isolated; they include insertion and deletion alleles. The dam locus maps at 75 min between cysG and aroB, similar to the Escherichia coli dam gene. Dam(-) mutants of S. typhimurium resemble those of E. coli in the following phenotypes: (1) increased spontaneous mutations, (2) moderate SOS induction, (3) enhancement of duplication segregation, (4) inviability of dam recA and dam recB mutants, and (5) suppression of the inviability of the dam recA and dam recB combinations by mutations that eliminate mismatch repair. However, differences between S. typhimurium and E. coli dam mutants are also found: (1) S. typhimurium dam mutants do not show increased UV sensitivity, suggesting that methyl-directed mismatch repair does not participate in the repair of UV-induced DNA damage in Salmonella. (2) S. typhimurium dam recJ mutants are viable, suggesting that the Salmonella RecJ function does not participate in the repair of DNA strand breaks formed in the absence of Dam methylation. We also describe a genetic screen for detecting novel genes regulated by Dam methylation and a locus repressed by Dam methylation in the S. typhimurium virulence (or ``cryptic'') plasmid. PMID:8878670

  7. Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer.

    PubMed

    O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica M J; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

    2015-10-01

    Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types. PMID:26330482

  8. [Identification of fish species based on ribosomal DNA ITS2 locus].

    PubMed

    Yuan, Wan-An

    2010-04-01

    To prevent illegal fishing and sale, the most difficult problem is identification of marketed fish species, especially the parts that are difficult to be differentiated with morphological method (e.g., larval, eggs, scales, meat, products etc. To assist conservation and management of fishery resources, this paper reported a molecular genetic approach based on ribosomal internal transcribed spacer 2 locus. The method includes two steps: (1) the order general primers were designed according to the conservative nature of 5.8SrRAN and 28SrRNA genes within an order, and the DNA ribosomal internal transcribed spacer 2 locus fragment were then amplified and sequenced. (2) The species-specific ladders and the species-specific primers for each species were designed according to the sequencing results. The map of molecular taxonomy was constructed. This approach employs multiplex PCR that is formatted for fish species identification. We tested 210 single-species samples and 40 mix-species samples from different regions of China. The approach distinguished accurately and sensitively samples from each of the five species. This genetic and molecular approach will be useful for fish conservation, assessment, management and exploitation, strengthen in law enforcement of fishery manager, combat rare and endangered fish smuggling, and prevent commercial fraud and biological invasion by harmful nonnative species.

  9. Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility

    PubMed Central

    Cook, James P; Morris, Andrew P

    2016-01-01

    Genome-wide association studies (GWAS) have traditionally been undertaken in homogeneous populations from the same ancestry group. However, with the increasing availability of GWAS in large-scale multi-ethnic cohorts, we have evaluated a framework for detecting association of genetic variants with complex traits, allowing for population structure, and developed a powerful test of heterogeneity in allelic effects between ancestry groups. We have applied the methodology to identify and characterise loci associated with susceptibility to type 2 diabetes (T2D) using GWAS data from the Resource for Genetic Epidemiology on Adult Health and Aging, a large multi-ethnic population-based cohort, created for investigating the genetic and environmental basis of age-related diseases.