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Sample records for locus genetics meets

  1. Genetic analysis of the claret locus of Drosophila melanogaster

    SciTech Connect

    Sequeira, W.; Nelson, C.R.; Szauter, P. )

    1989-11-01

    The claret (ca) locus of Drosophila melanogaster comprises two separately mutable domains, one responsible for eye color and one responsible for proper disjunction of chromosomes in meiosis and early cleavage divisions. Previously isolated alleles are of three types: (1) alleles of the claret (ca) type that affect eye color only, (2) alleles of the claret-nondisjunctional (ca{sup nd}) type that affect eye color and chromosome behavior, and (3) a meiotic mutation, non-claret disjunctional (ncd), that affects chromosome behavior only. In order to investigate the genetic structure of the claret locus, the authors have isolated 19 radiation-induced alleles of claret on the basis of the eye color phenotype. Two of these 19 new alleles are of the ca{sup nd} type, while 17 are of the ca type, demonstrating that the two domains do not often act as a single target for mutagenesis. This suggests that the two separately mutable functions are likely to be encoded by separate or overlapping genes rather than by a single gene. One of the new alleles of the ca{sup nd} type is a chromosome rearrangement with a breakpoint at the position of the claret locus. If this breakpoint is the cause of the mutant phenotype and there are no other mutations associated with the rearrangement, the two functions must be encoded by overlapping genes.

  2. Alpha-locus hexosaminidase genetic compound with juvenile gangliosidosis phenotype: clinical, genetic, and biochemical studies.

    PubMed Central

    Johnson, W G; Cohen, C S; Miranda, A F; Waran, S P; Chutorian, A M

    1980-01-01

    A 3-year-old boy developed progressive neurological deterioration in his third year, characterized by dementia, ataxia, myoclonic jerks, and bilateral macular cherry-red spots. Hexosaminidase A (HEX A) was partially decreased in the patient's serum, leukocytes, and cultured skin fibroblasts. Hexosaminidase was studied in serum and leukocytes from family members. Four members of the paternal branch appeared to be carriers of classical infantile Tay-Sachs allele, HEX alpha 2, probably receiving the gene from one great-grandparent of Ashkenazi origin. In the maternal branch, no one was a carrier of classical infantile Tay-Sachs disease, but five individuals were carriers of a milder alpha-locus defect. The patient, therefore, was a genetic compound of two different alpha-locus hexosaminidase mutations. At least 21 families with late-infantile or juvenile GM2 gangliosidosis have been reported, 18 of them with alpha-locus mutations, and three with beta-locus mutations. Genetic compounds of hexosaminidase have been reported in at least seven families, five with alpha-locus mutations and two with beta-locus mutations. The compound had the phenotype of infantile Tay-Sachs disease in one family, infantile Sandhoff disease in another, and the normal phenotype in the rest. PMID:6772023

  3. 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.

  4. Genetic Locus for Streptolysin S Production by Group A Streptococcus

    PubMed Central

    Nizet, Victor; Beall, Bernard; Bast, Darrin J.; Datta, Vivekananda; Kilburn, Laurie; Low, Donald E.; De Azavedo, Joyce C. S.

    2000-01-01

    Group A streptococcus (GAS) is an important human pathogen that causes pharyngitis and invasive infections, including necrotizing fasciitis. Streptolysin S (SLS) is the cytolytic factor that creates the zone of beta-hemolysis surrounding GAS colonies grown on blood agar. We recently reported the discovery of a potential genetic determinant involved in SLS production, sagA, encoding a small peptide of 53 amino acids (S. D. Betschel, S. M. Borgia, N. L. Barg, D. E. Low, and J. C. De Azavedo, Infect. Immun. 66:1671–1679, 1998). Using transposon mutagenesis, chromosomal walking steps, and data from the GAS genome sequencing project (www.genome.ou.edu/strep.html), we have now identified a contiguous nine-gene locus (sagA to sagI) involved in SLS production. The sag locus is conserved among GAS strains regardless of M protein type. Targeted plasmid integrational mutagenesis of each gene in the sag operon resulted in an SLS-negative phenotype. Targeted integrations (i) upstream of the sagA promoter and (ii) downstream of a terminator sequence after sagI did not affect SLS production, establishing the functional boundaries of the operon. A rho-independent terminator sequence between sagA and sagB appears to regulate the amount of sagA transcript produced versus transcript for the entire operon. Reintroduction of the nine-gene sag locus on a plasmid vector restored SLS activity to the nonhemolytic sagA knockout mutant. Finally, heterologous expression of the intact sag operon conferred the SLS beta-hemolytic phenotype to the nonhemolytic Lactococcus lactis. We conclude that gene products of the GAS sag operon are both necessary and sufficient for SLS production. Sequence homologies of sag operon gene products suggest that SLS is related to the bacteriocin family of microbial toxins. PMID:10858242

  5. Genetic locus for streptolysin S production by group A streptococcus.

    PubMed

    Nizet, V; Beall, B; Bast, D J; Datta, V; Kilburn, L; Low, D E; De Azavedo, J C

    2000-07-01

    Group A streptococcus (GAS) is an important human pathogen that causes pharyngitis and invasive infections, including necrotizing fasciitis. Streptolysin S (SLS) is the cytolytic factor that creates the zone of beta-hemolysis surrounding GAS colonies grown on blood agar. We recently reported the discovery of a potential genetic determinant involved in SLS production, sagA, encoding a small peptide of 53 amino acids (S. D. Betschel, S. M. Borgia, N. L. Barg, D. E. Low, and J. C. De Azavedo, Infect. Immun. 66:1671-1679, 1998). Using transposon mutagenesis, chromosomal walking steps, and data from the GAS genome sequencing project (www.genome.ou.edu/strep. html), we have now identified a contiguous nine-gene locus (sagA to sagI) involved in SLS production. The sag locus is conserved among GAS strains regardless of M protein type. Targeted plasmid integrational mutagenesis of each gene in the sag operon resulted in an SLS-negative phenotype. Targeted integrations (i) upstream of the sagA promoter and (ii) downstream of a terminator sequence after sagI did not affect SLS production, establishing the functional boundaries of the operon. A rho-independent terminator sequence between sagA and sagB appears to regulate the amount of sagA transcript produced versus transcript for the entire operon. Reintroduction of the nine-gene sag locus on a plasmid vector restored SLS activity to the nonhemolytic sagA knockout mutant. Finally, heterologous expression of the intact sag operon conferred the SLS beta-hemolytic phenotype to the nonhemolytic Lactococcus lactis. We conclude that gene products of the GAS sag operon are both necessary and sufficient for SLS production. Sequence homologies of sag operon gene products suggest that SLS is related to the bacteriocin family of microbial toxins.

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

    PubMed

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

    2015-10-01

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

  7. Molecular genetic analysis of the Phaseolus vulgaris P locus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Common bean market classes are distinguished by their many seed colors, patterns, and size. At least 23 genes, acting independently or in an epistatic manner, affect the seed coat color and pattern. The P locus which is described as the “ground factor” by Emerson, has multiple alleles and controls a...

  8. [The study of tomato fruit weight quantitative trait locus and its application in genetics teaching].

    PubMed

    Wang, Haiyan

    2015-08-01

    The classical research cases, which have greatly promoted the development of genetics in history, can be combined with the content of courses in genetics teaching to train students' ability of scientific thinking and genetic analysis. The localization and clone of gene controlling tomato fruit weight is a pioneer work in quantitative trait locus (QTL) studies and represents a complete process of QTL research in plants. Application of this integrated case in genetics teaching, which showed a wonderful process of scientific discovery and the fascination of genetic research, has inspired students' interest in genetics and achieved a good teaching effect.

  9. 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.

  10. Autosomal dominant ataxia: Genetic evidence for locus heterogeneity from a cuban founder-effect population

    PubMed Central

    Auburger, Georg; Diaz, Guillermo Orozco; Capote, Raul Ferreira; Sanchez, Suzana Gispert; Perez, Marta Paradoa; del Cueto, Marianela Estrada; Meneses, Mirna Garcia; Farrall, Martin; Williamson, Robert; Chamberlain, Susan; Baute, Luis Heredero

    1990-01-01

    The locus for autosomal dominant ataxia with a diagnosis of olivo-ponto-cerebellar atrophy at autopsy has been previously assigned to chromosome 6p. However, evidence for two alternative locations has been reported. We have recently described a large potential founder-effect population of such patients in the Holguin province of Cuba. With an estimated 1,000 patients available for analysis, this extensive cluster of families provides a unique opportunity for the definitive localization of the genetic mutation. Linkage analysis between the disease locus in this population and markers within and flanking the HLA region on chromosome 6 were undertaken in 12 families comprising over 100 affected individuals. Despite similarity in the clinical phenotype between those families where the disease locus has been reported to be linked to the HLA locus and the Cuban patients, no evidence of linkage to this region could be demonstrated in the latter. The disease locus was excluded from a 96-cM genetic interval of the short arm of chromosome 6, encompassing the F13A1–HLA–GLO1–MUT/D6S4 loci. These data strongly support the existence of genetic heterogeneity for the disease. PMID:1971152

  11. Genetic and Physical Variability at the Mating Type Locus of the Oomycete, Phytophthora Infestans

    PubMed Central

    Judelson, H. S.

    1996-01-01

    Mating type in the oomyceteous fungus, Phytophthora infestans, is determined by a single locus. In a previous study of a few isolates, the locus segregated in a manner genetically consistent with its linkage to a system of balanced lethal loci. To determine the prevalence of this phenomenon within P. infestans, genetic analyses were performed using isolates representative of the diversity within the species that had been selected by DNA fingerprinting using probes linked to mating type. Non-Mendelian segregation of the mating type locus was observed in crosses performed with each isolate. An unusual group of isolates was identified in which the mating type determinants had been rearranged within the genome; these strains also produced an aberrantly large number of self-fertile progeny. Curiously, in all isolates, markers linked to the mating type locus appeared prone to duplication, transposition, deletion, or other rearrangement. This was not observed for loci unlinked to mating type. Data from the crosses and analyses of marker variation were used to erect models to explain the bases of mating type determination and of the unusual segregation of the chromosomal region containing the mating type locus. PMID:8913745

  12. Genetic architecture and evolution of the S locus supergene in Primula vulgaris.

    PubMed

    Li, Jinhong; Cocker, Jonathan M; Wright, Jonathan; Webster, Margaret A; McMullan, Mark; Dyer, Sarah; Swarbreck, David; Caccamo, Mario; Oosterhout, Cock van; Gilmartin, Philip M

    2016-12-02

    Darwin's studies on heterostyly in Primula described two floral morphs, pin and thrum, with reciprocal anther and stigma heights that promote insect-mediated cross-pollination. This key innovation evolved independently in several angiosperm families. Subsequent studies on heterostyly in Primula contributed to the foundation of modern genetic theory and the neo-Darwinian synthesis. The established genetic model for Primula heterostyly involves a diallelic S locus comprising several genes, with rare recombination events that result in self-fertile homostyle flowers with anthers and stigma at the same height. Here we reveal the S locus supergene as a tightly linked cluster of thrum-specific genes that are absent in pins. We show that thrums are hemizygous not heterozygous for the S locus, which suggests that homostyles do not arise by recombination between S locus haplotypes as previously proposed. Duplication of a floral homeotic gene 51.7 million years (Myr) ago, followed by its neofunctionalization, created the current S locus assemblage which led to floral heteromorphy in Primula. Our findings provide new insights into the structure, function and evolution of this archetypal supergene.

  13. What to Expect When Meeting with a Genetic Counselor

    MedlinePlus

    ... Permissions What to Expect When Meeting With a Genetic Counselor Approved by the Cancer.Net Editorial Board , ... prevention, and treatment options and provide support. A genetic counselor’s training and certification A genetic counselor is ...

  14. An acid phosphatase locus expressed in mouse kidney (Apk) and its genetic location on chromosome 10.

    PubMed

    Womack, J E; Auerbach, S B

    1978-04-01

    A genetic locus controlling the electrophoretic mobility of an acid phosphatase in mouse kidney is described. This locus, called acid phosphatase-kidney (Apk), is not expressed in erythrocytes, liver, spleen, heart, lung, brain, skeletal muscle, stomach, or testes. The product of Apk hydrolyzes the substrate naphthol AS-MX phosphoric acid but is not active on alpha-naphthylphosphate or 4-methylumbelliferylphosphate. It is not inactivated by 50 C for 1 hr, nor is its electrophoretic mobility altered by incubation with neuraminidase. The locus is invariant among 31 inbred strains (Apka), with a variant allele (Apkm) observed only in Mus musculus molossinus. Codominant expression was observed in F1 hybrids of M. m. molossinus and inbred strains. Apk was mapped on Chr 10, near the neurological mutant waltzer (v).

  15. An entropy test for single-locus genetic association analysis

    PubMed Central

    2010-01-01

    Background The etiology of complex diseases is due to the combination of genetic and environmental factors, usually many of them, and each with a small effect. The identification of these small-effect contributing factors is still a demanding task. Clearly, there is a need for more powerful tests of genetic association, and especially for the identification of rare effects Results We introduce a new genetic association test based on symbolic dynamics and symbolic entropy. Using a freely available software, we have applied this entropy test, and a conventional test, to simulated and real datasets, to illustrate the method and estimate type I error and power. We have also compared this new entropy test to the Fisher exact test for assessment of association with low-frequency SNPs. The entropy test is generally more powerful than the conventional test, and can be significantly more powerful when the genotypic test is applied to low allele-frequency markers. We have also shown that both the Fisher and Entropy methods are optimal to test for association with low-frequency SNPs (MAF around 1-5%), and both are conservative for very rare SNPs (MAF<1%) Conclusions We have developed a new, simple, consistent and powerful test to detect genetic association of biallelic/SNP markers in case-control data, by using symbolic dynamics and symbolic entropy as a measure of gene dependence. We also provide a standard asymptotic distribution of this test statistic. Given that the test is based on entropy measures, it avoids smoothed nonparametric estimation. The entropy test is generally as good or even more powerful than the conventional and Fisher tests. Furthermore, the entropy test is more computationally efficient than the Fisher's Exact test, especially for large number of markers. Therefore, this entropy-based test has the advantage of being optimal for most SNPs, regardless of their allele frequency (Minor Allele Frequency (MAF) between 1-50%). This property is quite beneficial

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

    PubMed

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

    2012-08-01

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

  17. Genetic modifier loci of mouse Mfrp(rd6) identified by quantitative trait locus analysis.

    PubMed

    Won, Jungyeon; Charette, Jeremy R; Philip, Vivek M; Stearns, Timothy M; Zhang, Weidong; Naggert, Jürgen K; Krebs, Mark P; Nishina, Patsy M

    2014-01-01

    The identification of genes that modify pathological ocular phenotypes in mouse models may improve our understanding of disease mechanisms and lead to new treatment strategies. Here, we identify modifier loci affecting photoreceptor cell loss in homozygous Mfrp(rd6) mice, which exhibit a slowly progressive photoreceptor degeneration. A cohort of 63 F2 homozygous Mfrp(rd6) mice from a (B6.C3Ga-Mfrp(rd6)/J × CAST/EiJ) F1 intercross exhibited a variable number of cell bodies in the retinal outer nuclear layer at 20 weeks of age. Mice were genotyped with a panel of single nucleotide polymorphism markers, and genotypes were correlated with phenotype by quantitative trait locus (QTL) analysis to map modifier loci. A genome-wide scan revealed a statistically significant, protective candidate locus on CAST/EiJ Chromosome 1 and suggestive modifier loci on Chromosomes 6 and 11. Multiple regression analysis of a three-QTL model indicated that the modifier loci on Chromosomes 1 and 6 together account for 26% of the observed phenotypic variation, while the modifier locus on Chromosome 11 explains only an additional 4%. Our findings indicate that the severity of the Mfrp(rd6) retinal degenerative phenotype in mice depends on the strain genetic background and that a significant modifier locus on CAST/EiJ Chromosome 1 protects against Mfrp(rd6)-associated photoreceptor loss.

  18. 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.

  19. Genetic variation of the bronze locus (MC1R) in turkeys from Southern Brazil.

    PubMed

    Corso, Josmael; Hepp, Diego; Ledur, Mônica C; Peixoto, Jane O; Fagundes, Nelson J R; Freitas, Thales R O

    2017-03-20

    Domestic turkeys present several color phenotypes controlled by at least five genetic loci, but only one of these has been identified precisely: the bronze locus, which turned out to be the melanocortin-1 receptor (MC1R) gene. MC1R variation is important for breeders interested in maintaining or developing different color varieties. In this study, we sequenced most of the MC1R gene from 16 White Holland (the main commercial turkey variety) and 19 pigmented turkeys from southern Brazil with two purposes. The first was to describe the MC1R diversity in White Holland turkeys, which may serve as reservoirs of genetic diversity at this locus. The second was to test whether the traditional color classification used by Brazilian breeders is related to previously known MC1R alleles. White Holland turkeys had four different haplotypes corresponding to the bronze (b+) and black-winged bronze (b1) alleles. Pigmented turkeys also had four haplotypes corresponding to the b+ and b1 alleles, but different haplotypes represent the most common b+ allele in these two groups. The black (B) allele was absent from our samples. Overall, our results suggest that white and pigmented individuals form two different populations, and that the traditional color classification used by Brazilian breeders cannot accurately predict the genotypes at the bronze locus.

  20. Genetic variation of polymorphic NOS STR locus in ten Indian population groups.

    PubMed

    Shazia, A; Nithya, P; Seshadri, M

    2009-02-01

    The genotyping of 313 random individuals belonging to ten different population groups from three different states of India was performed for polymorphic pentanucleotide repeat present in the 5'-flanking region of nitric oxide synthase gene (NOS2A) to study the effect of geographical and linguistic affiliations on the genetic affinities among these groups. Likelihood ratio tests showed that all the ten populations for this locus were in Hardy Weinberg equilibrium. Eleven different alleles ranging from 7 repeat to 17 repeats and 46 different genotypes were observed. The observed and the expected heterozygosity ranged from 0.72-0.94 and 0.84-0.89, respectively. The discriminating power of this locus is > or = 0.86 and the polymorphism information content of this locus in ten population groups ranged from 0.80 to 0.85. High PIC, PD and PE value of this STR showed this marker to be informative and can be used for DNA typing and population studies. The eight populations from Kerala showed a lower GST value of 0.016 compared to the GST of ten populations (G(ST) = 0.019), thereby showing that the populations from the same state showed higher genetic proximity probably due to linguistic and geographical proximity between them.

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

    PubMed

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

    2016-11-03

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

  2. Genetic analysis of absB, a Streptomyces coelicolor locus involved in global antibiotic regulation.

    PubMed

    Adamidis, T; Champness, W

    1992-07-01

    The filamentous soil bacterium Streptomyces coelicolor is known to produce four antibiotics which are genetically and structurally distinct. An extensive search for antibiotic regulatory mutants led to the discovery of absB mutants, which are antibiotic deficient but sporulation proficient. Genetic analysis of the absB mutants has resulted in definition of the absB locus at 5 o'clock on the genetic map. Multiple cloned copies of the actII-ORF4 gene, an activator of synthesis of the antibiotic actinorhodin, restore actinorhodin biosynthetic capability to the absB mutants. These results are interpreted to mean that the failure of absB mutants to produce antibiotics results from decreased expression of the antibiotic genes. The absB gene is proposed to be involved in global regulation of antibiotic synthesis.

  3. Genetic control of natural killing and in vivo tumor elimination by the Chok locus.

    PubMed

    Idris, A H; Iizuka, K; Smith, H R; Scalzo, A A; Yokoyama, W M

    1998-12-21

    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.

  4. Statistical epistasis networks reduce the computational complexity of searching three-locus genetic models.

    PubMed

    Hu, Ting; Andrew, Angeline S; Karagas, Margaret R; Moore, Jason H

    2013-01-01

    The rapid development of sequencing technologies makes thousands to millions of genetic attributes available for testing associations with various biological traits. Searching this enormous high-dimensional data space imposes a great computational challenge in genome-wide association studies. We introduce a network-based approach to supervise the search for three-locus models of disease susceptibility. Such statistical epistasis networks (SEN) are built using strong pairwise epistatic interactions and provide a global interaction map to search for higher-order interactions by prioritizing genetic attributes clustered together in the networks. Applying this approach to a population-based bladder cancer dataset, we found a high susceptibility three-way model of genetic variations in DNA repair and immune regulation pathways, which holds great potential for studying the etiology of bladder cancer with further biological validations. We demonstrate that our SEN-supervised search is able to find a small subset of three-locus models with significantly high associations at a substantially reduced computational cost.

  5. A putative regulatory genetic locus modulates virulence in the pathogen Leptospira interrogans.

    PubMed

    Eshghi, Azad; Becam, Jérôme; Lambert, Ambroise; Sismeiro, Odile; Dillies, Marie-Agnès; Jagla, Bernd; Wunder, Elsio A; Ko, Albert I; Coppee, Jean-Yves; Goarant, Cyrille; Picardeau, Mathieu

    2014-06-01

    Limited research has been conducted on the role of transcriptional regulators in relation to virulence in Leptospira interrogans, the etiological agent of leptospirosis. Here, we identify an L. interrogans locus that encodes a sensor protein, an anti-sigma factor antagonist, and two genes encoding proteins of unknown function. Transposon insertion into the gene encoding the sensor protein led to dampened transcription of the other 3 genes in this locus. This lb139 insertion mutant (the lb139(-) mutant) displayed attenuated virulence in the hamster model of infection and reduced motility in vitro. Whole-transcriptome analyses using RNA sequencing revealed the downregulation of 115 genes and the upregulation of 28 genes, with an overrepresentation of gene products functioning in motility and signal transduction and numerous gene products with unknown functions, predicted to be localized to the extracellular space. Another significant finding encompassed suppressed expression of the majority of the genes previously demonstrated to be upregulated at physiological osmolarity, including the sphingomyelinase C precursor Sph2 and LigB. We provide insight into a possible requirement for transcriptional regulation as it relates to leptospiral virulence and suggest various biological processes that are affected due to the loss of native expression of this genetic locus.

  6. 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

  7. Multilocus patterns of genetic variation across Cryptosporidium species suggest balancing selection at the gp60 locus.

    PubMed

    Abal-Fabeiro, J L; Maside, X; Bello, X; Llovo, J; Bartolomé, C

    2013-09-01

    Cryptosporidium is an apicomplexan protozoan that lives in most vertebrates, including humans. Its gp60 gene is functionally involved in its attachment to host cells, and its high level of genetic variation has made it the reference marker for sample typing in epidemiological studies. To understand the origin of such high diversity and to determine the extent to which this classification applies to the rest of the genome, we analysed the patterns of variation at gp60 and nine other nuclear loci in isolates of three Cryptosporidium species. Most loci showed low genetic polymorphism (πS <1%) and similar levels of between-species divergence. Contrastingly, gp60 exhibited very different characteristics: (i) it was nearly ten times more variable than the other loci; (ii) it displayed a significant excess of polymorphisms relative to between-species differences in a maximum-likelihood Hudson-Kreitman-Aguadé test; (iii) gp60 subtypes turned out to be much older than the species they were found in; and (iv) showed a significant excess of polymorphic variants shared across species from random expectations. These observations suggest that this locus evolves under balancing selection and specifically under negative frequency-dependent selection (FDS). Interestingly, genetic variation at the other loci clusters very well within the groups of isolates defined by gp60 subtypes, which may provide new tools to understand the genome-wide patterns of genetic variation of the parasite in the wild. These results suggest that gp60 plays an active and essential role in the life cycle of the parasite and that genetic variation at this locus might be essential for the parasite's long-term success.

  8. A 27-locus STR assay to meet all United States and European law enforcement agency standards.

    PubMed

    Schumm, James W; Gutierrez-Mateo, Cristina; Tan, Eugene; Selden, Richard

    2013-11-01

    Different national and international agencies have selected specific STR sets for forensic database use. To enhance database comparison across national and international borders, a 27-locus multiplex system was developed comprising all 15 STR loci of the European standard set, the current 13 STR loci of the CODIS core, the proposed 22 STR loci of the expanded CODIS core, 4 additional commonly used STR loci, and the amelogenin locus. Development required iterative primer design to resolve primer-related artifacts, amplicon sizing, and locus-to-locus balance issues. The 19.5-min assay incorporated newly developed six-dye chemistry analyzed using a novel microfluidic electrophoresis instrument capable of simultaneous detection and discrimination of 8 or more fluorescent dyes. The 27-locus multiplex offers the potential for a new international STR standard permitting laboratories in any jurisdiction to use a single reaction to determine profiles for loci they typically generate plus an expanded common STR profiling set of global interest.

  9. Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment.

    PubMed

    Trampush, Joey W; Lencz, Todd; Knowles, Emma; Davies, Gail; Guha, Saurav; Pe'er, Itsik; Liewald, David C; Starr, John M; Djurovic, Srdjan; Melle, Ingrid; Sundet, Kjetil; Christoforou, Andrea; Reinvang, Ivar; Mukherjee, Semanti; DeRosse, Pamela; Lundervold, Astri; Steen, Vidar M; John, Majnu; Espeseth, Thomas; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G; Giegling, Ina; Konte, Bettina; Ikeda, Masashi; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E; Payton, Antony; Ollier, William; Horan, Mike; Scult, Matthew; Dickinson, Dwight; Straub, Richard E; Donohoe, Gary; Morris, Derek; Corvin, Aiden; Gill, Michael; Hariri, Ahmad; Weinberger, Daniel R; Pendleton, Neil; Iwata, Nakao; Darvasi, Ariel; Bitsios, Panos; Rujescu, Dan; Lahti, Jari; Le Hellard, Stephanie; Keller, Matthew C; Andreassen, Ole A; Deary, Ian J; Glahn, David C; Malhotra, Anil K

    2015-07-01

    Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47 × 10(-4) ) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94 × 10(-7) ), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65 × 10(-9) ). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness.

  10. Independent Evidence for an Association between General Cognitive Ability and a Genetic Locus for Educational Attainment

    PubMed Central

    Trampush, Joey W.; Lencz, Todd; Knowles, Emma; Davies, Gail; Guha, Saurav; Pe’er, Itsik; Liewald, David C.; Starr, John M.; Djurovic, Srdjan; Melle, Ingrid; Sundet, Kjetil; Christoforou, Andrea; Reinvang, Ivar; Mukherjee, Semanti; DeRosse, Pamela; Lundervold, Astri; Steen, Vidar M.; John, Majnu; Espeseth, Thomas; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G.; Giegling, Ina; Konte, Bettina; Ikeda, Masashi; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E.; Payton, Antony; Ollier, William; Horan, Mike; Scult, Matthew; Dickinson, Dwight; Straub, Richard E.; Donohoe, Gary; Morris, Derek; Corvin, Aiden; Gill, Michael; Hariri, Ahmad; Weinberger, Daniel R.; Pendleton, Neil; Iwata, Nakao; Darvasi, Ariel; Bitsios, Panos; Rujescu, Dan; Lahti, Jari; Le Hellard, Stephanie; Keller, Matthew C.; Andreassen, Ole A.; Deary, Ian J.; Glahn, David C.; Malhotra, Anil K.

    2015-01-01

    Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genomewide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability (“g”) in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47×10−4) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94×10−7), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65×10−9). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness. PMID:25951819

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

    PubMed Central

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

    1995-01-01

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

  12. A genetic locus essential for formate-dependent growth of Bradyrhizobium japonicum.

    PubMed Central

    McClung, C R; Chelm, B K

    1987-01-01

    A genetic locus essential for the formate-dependent growth of Bradyrhizobium japonicum was isolated by complementation of ethyl methanesulfonate-induced mutants with a cosmid gene library of B. japonicum DNA. Three related cosmids containing 18.7 kilobase pairs of B. japonicum DNA in common were identified as being able to restore formate-dependent growth capability to mutants lacking either ribulosebisphosphate carboxylase or both ribulosebisphosphate carboxylase and phosphoribulokinase activities. To further localize the complementing gene(s), a series of four deletions spanning a total of 16.1 kilobase pairs were introduced into the B. japonicum chromosome. Each resulting deletion mutant lacked formate dehydrogenase activity and lacked ribulosebisphosphate carboxylase activity and immunologically detectable protein. Three of the four also lacked phosphoribulokinase activity. Two other mutants in which the deletion-bearing recombinant plasmid had integrated into the chromosome also lacked ribulosebisphosphate carboxylase activity and protein and phosphoribulokinase activities. The genetic locus defined by these mutants could contain the structural genes for these enzymes or a regulatory gene(s) controlling their expression or both. Images PMID:3036781

  13. Genetic organization and molecular characterization of secA2 locus in Listeria species.

    PubMed

    Mishra, Krishna K; Mendonca, Marcelo; Aroonnual, Amornrat; Burkholder, Kristin M; Bhunia, Arun K

    2011-12-10

    The translocation of proteins across the bacterial cell wall is carried out by the general secretory (Sec) system. Most bacteria have a single copy of the secA gene, with the exception of a few Gram-positive bacteria, which have an additional copy of secA, designated secA2. secA2 is present in Listeria monocytogenes and is responsible for secretion and translocation of several proteins including virulence factors; however, little is known about the secA2 gene and its genetic organization in nonpathogenic members of the genus Listeria. The goal of this study was to determine the presence of secA2 locus and analyze the genetic relatedness among pathogenic and nonpathogenic Listeria species. Cloning experiments revealed that secA2 is present in all analyzed pathogenic (L. monocytogenes and L. ivanovii) and nonpathogenic (L. welshimeri, L. innocua, L. seeligeri, L. grayi and L. marthii) Listeria species except L. rocourtiae. Likewise, SecA2 transcripts were also detected in all species. Sequence analysis further revealed that 2331 nucleotides (776 amino acids) are conserved in L. monocytogenes, L. welshimeri, L. innocua and L. marthii. Three nucleotides are deleted in L. ivanovii and L. seeligeri and six in L. grayi, resulting in amino acid counts of 775, 775 and 774, respectively. secA2 is flanked upstream by iap (encoding p60) and downstream by a putative membrane protein (lmo0583, lmo f2365_0613) in all analyzed Listeria species, demonstrating conserved genetic organization of the secA2 locus in pathogenic and nonpathogenic species. Deletion of secA2 in L. innocua impaired accumulation of SecA2 substrate, N-acetyl muramidase (NamA) in the cell wall, providing evidence for the presence of functional SecA2 in nonpathogenic Listeria.

  14. Heterochromatic Position Effect at the Rosy Locus of DROSOPHILA MELANOGASTER: Cytological, Genetic and Biochemical Characterization

    PubMed Central

    Rushlow, C. A.; Chovnick, A.

    1984-01-01

    This report describes cytological, genetic and biochemical studies designed to characterize two γ-radiation induced, apparent "underproducer" variants of the rosy locus (ry:3-52.0), ryps1149 and ryps11136. The following observations provide a compelling basis for their diagnosis as heterochromatic position effect variants. (1) They are associated with rearrangements that place heterochromatin adjacent to the rosy region of chromosome 3 (87D). (2) The effect of these mutations on rosy locus expression is subject to modification by abnormal Y chromosome content. (3) The rearrangement alters only the expression of the rosy allele on the same chromosome (cis-acting). (4) The Y chromosome modification is only on the position-affected allele's expression. (5) The recessive lethality associated with the rearrangements relate to specific rosy region vital loci, and for ryps 11136, the lethality is not Y chromosome modified. (6) The peptide product of the position-affected allele is qualitatively normal by several criteria. (7) Heterozygous deletion of 87E2-F2 is a suppressor of the rosy position effect. (8) The rosy position effect on XDH production may be assayed in whole larvae and larval fat body tissue as well as in adults. PMID:6437902

  15. 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

  16. 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.

  17. 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

  18. Global Genetic Architecture of an Erythroid Quantitative Trait Locus, HMIP-2

    PubMed Central

    Menzel, Stephan; Rooks, Helen; Zelenika, Diana; Mtatiro, Siana N; Gnanakulasekaran, Akshala; Drasar, Emma; Cox, Sharon; Liu, Li; Masood, Mariam; Silver, Nicholas; Garner, Chad; Vasavda, Nisha; Howard, Jo; Makani, Julie; Adekile, Adekunle; Pace, Betty; Spector, Tim; Farrall, Martin; Lathrop, Mark; Thein, Swee Lay

    2014-01-01

    HMIP-2 is a human quantitative trait locus affecting peripheral numbers, size and hemoglobin composition of red blood cells, with a marked effect on the persistence of the fetal form of hemoglobin, HbF, in adults. The locus consists of multiple common variants in an enhancer region for MYB (chr 6q23.3), which encodes the hematopoietic transcription factor cMYB. Studying a European population cohort and four African-descended groups of patients with sickle cell anemia, we found that all share a set of two spatially separate HbF-promoting alleles at HMIP-2, termed “A” and “B.” These typically occurred together (“A–B”) on European chromosomes, but existed on separate homologous chromosomes in Africans. Using haplotype signatures for “A” and “B,” we interrogated public population datasets. Haplotypes carrying only “A” or “B” were typical for populations in Sub-Saharan Africa. The “A–B” combination was frequent in European, Asian, and Amerindian populations. Both alleles were infrequent in tropical regions, possibly undergoing negative selection by geographical factors, as has been reported for malaria with other hematological traits. We propose that the ascertainment of worldwide distribution patterns for common, HbF-promoting alleles can aid their further genetic characterization, including the investigation of gene–environment interaction during human migration and adaptation. PMID:25069958

  19. Multiple-locus variable number tandem repeats analysis for genetic fingerprinting of pathogenic bacteria.

    PubMed

    Lindstedt, Bjørn-Arne

    2005-06-01

    DNA fingerprinting has attracted considerable interest as means for identifying, tracing and preventing the dissemination of infectious agents. Various methods have been developed for typing of pathogenic bacteria, which differ in discriminative power, reproducibility and ease of interpretation. During recent years a typing method, which uses the information provided by whole genome sequencing of bacterial species, has gained increased attention. Short sequence repeat (SSR) motifs are known to undergo frequent variation in the number of repeated units through cellular mechanisms most commonly active during chromosome replication. A class of SSRs, named variable number of tandem repeats (VNTRs), has proven to be a suitable target for assessing genetic polymorphisms within bacterial species. This review attempts to give an overview of bacterial agents where VNTR-based typing, or multiple-locus variant-repeat analysis (MLVA) has been developed for typing purposes, together with addressing advantages and drawbacks associated with the use of tandem repeated DNA motifs as targets for bacterial typing and identification.

  20. The population genetics of the alpha-2 globin locus of orangutans (Pongo pygmaeus).

    PubMed

    Steiper, Michael E; Wolfe, Nathan D; Karesh, William B; Kilbourn, Annelisa M; Bosi, Edwin J; Ruvolo, Maryellen

    2005-03-01

    In this study, the molecular population genetics of the orangutan's alpha-2 globin (HBA2) gene were investigated in order to test for the action of natural selection. Haplotypes from 28 orangutan chromosomes were collected from a 1.46-kilobase region of the alpha-2 globin locus. While many aspects of the data were consistent with neutrality, the observed heterogeneous distribution of polymorphisms was inconsistent with neutral expectations. Furthermore, a single amino acid variant, found in both the Bornean and the Sumatran orangutan subspecies, was associated with different alternative synonymous variants in each subspecies, suggesting that the allele may have spread separately through the two subspecies after two distinct origination events. This variant is not in Hardy-Weinberg equilibrium (HWE). These observations are consistent with neutral models that incorporate population structure and models that invoke selection. The orangutan Plasmodium parasite is a plausible selective agent that may underlie the variation at alpha-2 globin in orangutans.

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

    PubMed Central

    Cheney, R W; Kredich, N M

    1975-01-01

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

  2. Genetic polymorphisms of the CST2 locus coding for cystatin SA.

    PubMed

    Shintani, M; Minaguchi, K; Isemura, S; Saitoh, E; Sanada, K; Semba, T

    1994-07-01

    A new genetic polymorphism of cystatin SA has been identified in human submandibular-sublingual saliva by means of basic gel electrophoresis and immunoblotting with anti-cystatin S. Two proteins, SA1 and SA2, are given by two alleles of CST2, viz., CST2*1 and CST*2. Inheritance is controlled by two codominant alleles at an autosomal locus. This hypothesis is supported by studies of 16 families 32 children. Gene frequencies for CST2*1 and CST2*2 are 0.935 and 0.065, respectively (n = 341). Eighteen amino acids determined among 20 N-terminal residues of cystatin SA2 are identical with the sequence encoded by CST2. Three forms of cystatin S (mono-phosphorylated cystatin S, di-phosphorylated cystatin S, and non-phosphorylated cystatin S) are present in the 341 saliva samples tested.

  3. The locus of evolution: evo devo and the genetics of adaptation.

    PubMed

    Hoekstra, Hopi E; Coyne, Jerry A

    2007-05-01

    An important tenet of evolutionary developmental biology ("evo devo") is that adaptive mutations affecting morphology are more likely to occur in the cis-regulatory regions than in the protein-coding regions of genes. This argument rests on two claims: (1) the modular nature of cis-regulatory elements largely frees them from deleterious pleiotropic effects, and (2) a growing body of empirical evidence appears to support the predominant role of gene regulatory change in adaptation, especially morphological adaptation. Here we discuss and critique these assertions. We first show that there is no theoretical or empirical basis for the evo devo contention that adaptations involving morphology evolve by genetic mechanisms different from those involving physiology and other traits. In addition, some forms of protein evolution can avoid the negative consequences of pleiotropy, most notably via gene duplication. In light of evo devo claims, we then examine the substantial data on the genetic basis of adaptation from both genome-wide surveys and single-locus studies. Genomic studies lend little support to the cis-regulatory theory: many of these have detected adaptation in protein-coding regions, including transcription factors, whereas few have examined regulatory regions. Turning to single-locus studies, we note that the most widely cited examples of adaptive cis-regulatory mutations focus on trait loss rather than gain, and none have yet pinpointed an evolved regulatory site. In contrast, there are many studies that have both identified structural mutations and functionally verified their contribution to adaptation and speciation. Neither the theoretical arguments nor the data from nature, then, support the claim for a predominance of cis-regulatory mutations in evolution. Although this claim may be true, it is at best premature. Adaptation and speciation probably proceed through a combination of cis-regulatory and structural mutations, with a substantial contribution of

  4. A candidate syntenic genetic locus is associated with voluntary exercise levels in mice and humans.

    PubMed

    Kostrzewa, E; Brandys, M K; van Lith, H A; Kas, M J H

    2015-01-01

    Individual levels of physical activity, and especially of voluntary physical exercise, highly contribute to the susceptibility for developing metabolic, cardiovascular diseases, and potentially to psychiatric disorders. Here, we applied a cross-species approach to explore a candidate genetic region for voluntary exercise levels. First, a panel of mouse chromosome substitution strains was used to map a genomic region on mouse chromosome 2 that contributes to voluntary wheel running levels - a behavioral readout considered a model of voluntary exercise in humans. Subsequently, we tested the syntenic region (HSA20: 51,212,545-55,212,986) in a human sample (Saint Thomas Twin Register; n=3038) and found a significant association between voluntary exercise levels (categorized into excessive and non-excessive exercise) and an intergenic SNP rs459465 (adjusted P-value of 0.001). Taking under consideration the methodological challenges embedded in this translational approach in the research of complex phenotypes, we wanted to further test the validity of this finding. Therefore, we repeated the analysis in an independent human population (ALSPAC data set; n=2557). We found a significant association of excessive exercise with two SNPs in the same genomic region (rs6022999, adjusted P-value of P=0.011 and rs6092090, adjusted P-value of 0.012). We explored the locus for possible candidate genes by means of literature search and bioinformatics analysis of gene function and of trans-regulatory elements. We propose three potential human candidate genes for voluntary physical exercise levels (MC3R, CYP24A1, and GRM8). To conclude, the identified genetic variance in the human locus 20q13.2 may affect voluntary exercise levels.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. Philosophy of race meets population genetics.

    PubMed

    Spencer, Quayshawn

    2015-08-01

    In this paper, I respond to four common semantic and metaphysical objections that philosophers of race have launched at scholars who interpret recent human genetic clustering results in population genetics as evidence for biological racial realism. I call these objections 'the discreteness objection', 'the visibility objection', 'the very important objection', and 'the objectively real objection.' After motivating each objection, I show that each one stems from implausible philosophical assumptions about the relevant meaning of 'race' or the nature of biological racial realism. In order to be constructive, I end by offering some advice for how we can productively critique attempts to defend biological racial realism based on recent human genetic clustering results. I also offer a clarification of the relevant human-population genetic research.

  7. 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...

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

    PubMed Central

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

    2010-01-01

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

  9. Genetics meets pathology - an increasingly important relationship.

    PubMed

    Bonthron, David T; Foulkes, William D

    2017-01-01

    The analytical power of modern methods for DNA analysis has outstripped our capability to interpret and understand the data generated. To make good use of this genomic data in a biomedical setting (whether for research or diagnosis), it is vital that we understand the mechanisms through which mutations affect biochemical pathways and physiological systems. This lies at the centre of what genetics is all about, and it is the reason why genetics and genomics should go hand in hand whenever possible. In this Annual Review Issue of The Journal of Pathology, we have assembled a collection of 16 expert reviews covering a wide range of topics. Through these, we illustrate the power of genetic analysis to improve our understanding of normal physiology and disease pathology, and thereby to think in rational ways about clinical management. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  10. Evidence for weak genetic recombination at the PTP2 locus of Nosema ceranae.

    PubMed

    Gómez-Moracho, Tamara; Bartolomé, Carolina; Martín-Hernández, Raquel; Higes, Mariano; Maside, Xulio

    2015-04-01

    The microsporidian Nosema ceranae is an emergent pathogen that threatens the health of honeybees and other pollinators all over the world. Its recent rapid spread across a wide variety of host species and environments demonstrated an enhanced ability of adaptation, which seems to contradict the lack of evidence for genetic recombination and the absence of a sexual stage in its life cycle. Here we retrieved fresh data of the patterns of genetic variation at the PTP2 locus in naturally infected Apis mellifera colonies, by means of single genome amplification. This technique, designed to prevent the formation of chimeric haplotypes during polymerase chain reaction (PCR), provides more reliable estimates of the diversity levels and haplotype structure than standard PCR-cloning methods. Our results are consistent with low but significant rates of recombination in the history of the haplotypes detected: estimates of the population recombination rate are of the order of 30 and support recent evidence for unexpectedly high levels of variation of the parasites within honeybee colonies. These observations suggest the existence of a diploid stage at some point in the life cycle of this parasite and are relevant for our understanding of the dynamics of its expanding population.

  11. The Salmonella typhimurium mar locus: molecular and genetic analyses and assessment of its role in virulence.

    PubMed Central

    Sulavik, M C; Dazer, M; Miller, P F

    1997-01-01

    The marRAB operon is a regulatory locus that controls multiple drug resistance in Escherichia coli. marA encodes a positive regulator of the antibiotic resistance response, acting by altering the expression of unlinked genes. marR encodes a repressor of marRAB transcription and controls the production of MarA in response to environmental signals. A molecular and genetic study of the homologous operon in Salmonella typhimurium was undertaken, and the role of marA in virulence in a murine model was assessed. Expression of E. coli marA (marAEC) present on a multicopy plasmid in S. typhimurium resulted in a multiple antibiotic resistance (Mar) phenotype, suggesting that a similar regulon exists in this organism. A genomic plasmid library containing S. typhimurium chromosomal sequences was introduced into an E. coli strain that was deleted for the mar locus and contained a single-copy marR'-'lacZ translational fusion. Plasmid clones that contained both S. typhimurium marR (marRSt) and marA (marASt) genes were identified as those that were capable of repressing expression of the fusion and which resulted in a Mar phenotype. The predicted amino acid sequences of MarRSt, MarASt, and MarBSt were 91, 86, and 42% identical, respectively, to the same genes from E. coli, while the operator/promoter region of the operon was 86% identical to the same 98-nucleotide-upstream region in E. coli. The marRAB transcriptional start sites for both organisms were determined by primer extension, and a marRABSt transcript of approximately 1.1 kb was identified by Northern blot analysis. Its accumulation was shown to be inducible by sodium salicylate. Open reading frames flanking the marRAB operon were also conserved. An S. typhimurium marA disruption strain was constructed by an allelic exchange method and compared to the wild-type strain for virulence in a murine BALB/c infection model. No effect on virulence was noted. The endogenous S. typhimurium plasmid that is associated with virulence

  12. Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide.

    PubMed

    Gotschlich, E C

    1994-12-01

    A locus involved in the biosynthesis of gonococcal lipooligosaccharide (LOS) has been cloned from gonococcal strain F62. The locus contains five open reading frames. The first and second reading frames are homologous, but not identical, to the fourth and fifth reading frames, respectively. Interposed is an additional reading frame which has distant homology to the Escherichia coli rfaI and rfaI genes, both glucosyl transferases involved in lipopolysaccharide core biosynthesis. The second and fifth reading frames show strong homology to the lex-1 or lic2A gene of Haemophilus influenzae, but do not contain the CAAT repeats found in this gene. Deletions of each of these five genes, of combinations of genes, and of the entire locus were constructed and introduced into parental gonococcal strain F62 by transformation. The LOS phenotypes were then analyzed by SDS-PAGE and reactivity with monoclonal antibodies. Analysis of the gonococcal mutants indicates that four of these genes are the glycosyl transferases that add GalNAc beta 1-->3Gal beta 1-->4GlcNAc beta 1-->3 Gal beta 1--4 to the substrate Glc beta 1-->4Hep--R of the inner core region. The gene with homology to E. coli rfaI/rfaI is involved with the addition of the alpha-linked galactose residue in the biosynthesis of the alternative LOS structure Gal alpha 1-->4Gal beta 1-->4Glc beta 1-->4Hep-->R. Since these genes encode LOS glycosyl transferases they have been named lgtA, lgtB, lgtC, lgtD, and lgtE. The DNA sequence analysis revealed that lgtA, lgtC, and lgtD contained poly-G tracts, which, in strain F62 were, respectively, 17, 10, and 11 bp. Thus, three of the LOS biosynthetic enzymes are potentially susceptible to premature termination by reading frame changes. It is likely that these structural features are responsible for the high-frequency genetic variation of gonococcal LOS.

  13. Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide

    PubMed Central

    1994-01-01

    A locus involved in the biosynthesis of gonococcal lipooligosaccharide (LOS) has been cloned from gonococcal strain F62. The locus contains five open reading frames. The first and second reading frames are homologous, but not identical, to the fourth and fifth reading frames, respectively. Interposed is an additional reading frame which has distant homology to the Escherichia coli rfaI and rfaI genes, both glucosyl transferases involved in lipopolysaccharide core biosynthesis. The second and fifth reading frames show strong homology to the lex-1 or lic2A gene of Haemophilus influenzae, but do not contain the CAAT repeats found in this gene. Deletions of each of these five genes, of combinations of genes, and of the entire locus were constructed and introduced into parental gonococcal strain F62 by transformation. The LOS phenotypes were then analyzed by SDS-PAGE and reactivity with monoclonal antibodies. Analysis of the gonococcal mutants indicates that four of these genes are the glycosyl transferases that add GalNAc beta 1-->3Gal beta 1-->4GlcNAc beta 1-->3 Gal beta 1--4 to the substrate Glc beta 1-->4Hep--R of the inner core region. The gene with homology to E. coli rfaI/rfaI is involved with the addition of the alpha-linked galactose residue in the biosynthesis of the alternative LOS structure Gal alpha 1-->4Gal beta 1-->4Glc beta 1-->4Hep-->R. Since these genes encode LOS glycosyl transferases they have been named lgtA, lgtB, lgtC, lgtD, and lgtE. The DNA sequence analysis revealed that lgtA, lgtC, and lgtD contained poly-G tracts, which, in strain F62 were, respectively, 17, 10, and 11 bp. Thus, three of the LOS biosynthetic enzymes are potentially susceptible to premature termination by reading frame changes. It is likely that these structural features are responsible for the high-frequency genetic variation of gonococcal LOS. PMID:7964493

  14. PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance

    PubMed Central

    Tucker, Nathan R.; Castro-Vega, Luis-Jaime; Katz, Alexander; D’Escamard, Valentina; Tréard, Cyrielle; Fraher, Daniel; Albuisson, Juliette; Kadian-Dodov, Daniella; Ye, Zi; Austin, Erin; Yang, Min-Lee; Hunker, Kristina; Cusi, Daniele; Galan, Pilar; Empana, Jean-Philippe; Jouven, Xavier; Gimenez-Roqueplo, Anne-Paule; Bruneval, Patrick; Hyun Kim, Esther Soo; Olin, Jeffrey W.; Azizi, Michel; Plouin, Pierre-François; Ellinor, Patrick T.; Kullo, Iftikhar J.; Milan, David J.; Ganesh, Santhi K.; Boutouyrie, Pierre; Bouatia-Naji, Nabila

    2016-01-01

    Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD is often an underdiagnosed cause of hypertension and stroke, has higher prevalence in females (~80%) but its pathophysiology is unclear. We analyzed ~26K common variants (MAF>0.05) generated by exome-chip arrays in 249 FMD patients and 689 controls. We replicated 13 loci (P<10−4) in 402 cases and 2,537 controls and confirmed an association between FMD and a variant in the phosphatase and actin regulator 1 gene (PHACTR1). Three additional case control cohorts including 512 cases and 669 replicated this result and overall reached the genomic level of significance (OR = 1.39, P = 7.4×10−10, 1,154 cases and 3,895 controls). The top variant, rs9349379, is intronic to PHACTR1, a risk locus for coronary artery disease, migraine, and cervical artery dissection. The analyses of geometrical parameters of carotids from ~2,500 healthy volunteers indicate higher intima media thickness (P = 1.97×10−4) and wall to lumen ratio (P = 0.002) in rs9349379-A carriers, suggesting indices of carotid hypertrophy previously described in carotids of FMD patients. Immunohistochemistry detected PHACTR1 in endothelium and smooth muscle cells of FMD and normal human carotids. The expression of PHACTR1 by genotypes in primary human fibroblasts showed higher expression in rs9349379-A carriers (N = 86, P = 0.003). Phactr1 knockdown in zebrafish resulted in dilated vessels indicating subtle impaired vascular development. We report the first susceptibility locus for FMD and provide evidence for a complex genetic pattern of inheritance and indices of shared pathophysiology between FMD and other cardiovascular and neurovascular diseases. PMID:27792790

  15. Genetic control of pungency in C. chinense via the Pun1 locus.

    PubMed

    Stewart, Charles; Mazourek, Michael; Stellari, Giulia M; O'Connell, Mary; Jahn, Molly

    2007-01-01

    Capsaicin, the pungent principle in hot peppers, acts to deter mammals from consuming pungent pepper pods. Capsaicinoid biosynthesis is restricted to the genus Capsicum and results from the acylation of the aromatic compound, vanillylamine, with a branched-chain fatty acid. The presence of capsaicinoids is controlled by the Pun1 locus, which encodes a putative acyltransferase. In its homozygous recessive state, pun1/pun1, capsaicinoids are not produced by the pepper plant. HPLC analysis confirmed that capsaicinoids are only found in the interlocular septa of pungent pepper fruits. Immunolocalization studies showed that capsaicinoid biosynthesis is uniformly distributed across the epidermal cells of the interlocular septum. Capsaicinoids are secreted from glandular epidermal cells into subcuticular cavities that swell to form blisters along the epidermis. Blister development is positively associated with capsaicinoid accumulation and blisters are not present in non-pungent fruit. A genetic study was used to determine if the absence of blisters in non-pungent fruit acts independently of Pun1 to control pungency. Screening of non-pungent germplasm and genetic complementation tests identified a previously unknown recessive allele of Pun1, named pun1(2). Sequence analysis of pun1(2) revealed that a four base pair deletion results in a frameshift mutation and the predicted production of a truncated protein. Genetic analysis revealed that pun1(2) co-segregated exactly with the absence of blisters, non-pungency, and a reduced transcript accumulation of several genes involved in capsaicinoid biosynthesis. Collectively, these results establish that blister formation requires the Pun1 allele and that pun1(2) is a recessive allele from C. chinense that results in non-pungency.

  16. Interacting personalities: behavioural ecology meets quantitative genetics.

    PubMed

    Dingemanse, Niels J; Araya-Ajoy, Yimen G

    2015-02-01

    Behavioural ecologists increasingly study behavioural variation within and among individuals in conjunction, thereby integrating research on phenotypic plasticity and animal personality within a single adaptive framework. Interactions between individuals (cf. social environments) constitute a major causative factor of behavioural variation at both of these hierarchical levels. Social interactions give rise to complex 'interactive phenotypes' and group-level emergent properties. This type of phenotype has intriguing evolutionary implications, warranting a cohesive framework for its study. We detail here how a reaction-norm framework might be applied to usefully integrate social environment theory developed in behavioural ecology and quantitative genetics. The proposed emergent framework facilitates firm integration of social environments in adaptive research on phenotypic characters that vary within and among individuals.

  17. Genetic changes at the transferrin locus in the red-backed vole (Clethrionomys gapperi)

    SciTech Connect

    Mihok, S.; Fuller, W.A.; Canham, R.P.; McPhee, E.C.

    1983-01-01

    Genetic changes at the transferrin locus in Clethrionomys gapperi were intermittently monitored in a subarctic population from 1966 to 1978. Over this 13-year period, only minor fluctuations in gene frequency were observed. Gene frequency of Tf/sup J/ increased over winter during declines from high nonbreeding density in autumn. This phenomenon may have been responsible for a general negative correlation between the frequency of Tf/sup J/ and population density. Outside of winter, no frequency changes were detected within trappable age-classes of voles from relatively discrete seasonal generations. Excess of Tf/sup M/J/ heterozygotes occurred in three of four samples of young voles that matured in the year of their birth. A similar heterozygote excess occurred in one of six samples of overwintered voles taken in a year characterized by a high rate of population growth. These results suggest that selection may occur during ecologically different conditions of high density or population growth. A heterozygote advantage in early-season cohorts may account for the maintenance of transferrin polymorphism. This hypothesis requires further data on the breeding structure and early life history of voles.

  18. Genetic Control of Pheromones in Drosophila Simulans. I. Ngbo, a Locus on the Second Chromosome

    PubMed Central

    Ferveur, J. F.

    1991-01-01

    7-Tricosene and 7-pentacosene are predominant hydrocarbons on the cuticle of both sexes in Drosophila simulans. The pheromonal role of 7-tricosene has been clearly established for conspecific males, while a synergistic effect for 7-pentacosene has been postulated. Interstrain variation for the production of both compounds is very marked, but similar for both sexes. The genetic basis of this polymorphism was investigated. A major role was found for the second chromosome, which controls the 7-tricosene:7-pentacosene ratio. The main locus involved in controlling this variation, Ngbo, was mapped to position 65.3 on the second chromosome. The production of 7-pentacosene is directly related to the Ngbo genotype, which is additively expressed with two known alleles, Seychelles and Cameroon. These alleles act codominantly and are, respectively, hypomorphic and hypermorphic with regard to their effect on 7-pentacosene production. The production of 7-tricosene, which is partially inversely related to that of 7-pentacosene, is also affected by secondary interactions with the second chromosome and with the autosomal background. PMID:2071017

  19. Genetic structure of the mating-type locus of Chlamydomonas reinhardtii.

    PubMed Central

    Ferris, Patrick J; Armbrust, E Virginia; Goodenough, Ursula W

    2002-01-01

    Portions of the cloned mating-type (MT) loci (mt(+) and mt(-)) of Chlamydomonas reinhardtii, defined as the approximately 1-Mb domains of linkage group VI that are under recombinational suppression, were subjected to Northern analysis to elucidate their coding capacity. The four central rearranged segments of the loci were found to contain both housekeeping genes (expressed during several life-cycle stages) and mating-related genes, while the sequences unique to mt(+) or mt(-) carried genes expressed only in the gametic or zygotic phases of the life cycle. One of these genes, Mtd1, is a candidate participant in gametic cell fusion; two others, Mta1 and Ezy2, are candidate participants in the uniparental inheritance of chloroplast DNA. The identified housekeeping genes include Pdk, encoding pyruvate dehydrogenase kinase, and GdcH, encoding glycine decarboxylase complex subunit H. Unusual genetic configurations include three genes whose sequences overlap, one gene that has inserted into the coding region of another, several genes that have been inactivated by rearrangements in the region, and genes that have undergone tandem duplication. This report extends our original conclusion that the MT locus has incurred high levels of mutational change. PMID:11805055

  20. Molecular genetic analysis of the cytochrome P450-debrisoquine hydroxylase locus and association with cancer susceptibility.

    PubMed Central

    Smith, C A; Moss, J E; Gough, A C; Spurr, N K; Wolf, C R

    1992-01-01

    The cytochrome P450-dependent monooxygenases play a central role in the metabolism of chemical carcinogens. The action of these enzymes can lead to either carcinogen detoxication or activation. Differences in P450 expression in animal models give rise to large differences in susceptibility to chemical carcinogens, so genetic polymorphisms in P450 expression may be expected to be an important factor in individual human susceptibility to cancer. Of particular interest is the genetic polymorphism at the cytochrome P450-debrisoquine/sparteine hydroxylase locus (CYP2D6). Although this is a minor liver P450, its polymorphic expression is associated with the abnormal metabolism of at least 30 therapeutic drugs, including beta-blockers and tricyclic antidepressants. Conflicting reports have been made on the association of this polymorphism with cancer susceptibility. This disagreement may be attributable to limitations of the phenotyping assay used to identify affected individuals (poor metabolizers, PMs). In order to clarify these anomalies, we have developed a simple DNA-based assay with which we can identify the majority of PMs. The assay is centered around the primary gene defect responsible for the polymorphism, a G to A transition at the junction of intron 3/exon 4 which results in a frame-shift in the resultant mRNA. The frequency of this mutation is 70-80% in PMs. We have studied the frequency of mutated alleles in a control population and in a wide range of cancer patients. No association between this polymorphism and lung cancer susceptibility was observed; however, in other populations of cancer patients some very interesting shifts were found in the proportion of PMs and heterozygotes from that in the normal population. PMID:1486838

  1. Genetic variation at the delta-sarcoglycan (SGCD) locus elevates heritable sympathetic nerve activity in human twin pairs.

    PubMed

    Hightower, C Makena; Zhang, Kuixing; Miramontes-González, José P; Rao, Fangwen; Wei, Zhiyun; Schork, Andrew J; Nievergelt, Caroline M; Biswas, Nilima; Mahata, Manjula; Elkelis, Nina; Taupenot, Laurent; Stridsberg, Mats; Ziegler, Michael G; O'Connor, Daniel T

    2013-12-01

    The Syrian Cardiomyopathic Hamster (BIO-14.6/53.58 strains) model of cardiac failure, resulting from naturally occurring deletion at the SGCD (delta-sarcoglycan) locus, displays widespread disturbances in catecholamine metabolism. Rare Mendelian myopathy disorders of human SGCD occur, although common naturally occurring SGCD genetic variation has not been evaluated for effects on human norepinephrine (NE) secretion. This study investigated the effect of SGCD genetic variation on control of NE secretion in healthy twin pairs. Genetic associations profiled SNPs across the SGCD locus. Trait heritability (h(2)) and genetic covariance (pleiotropy; shared h(2)) were evaluated. Sympathochromaffin exocytosis in vivo was probed in plasma by both catecholamines and Chromogranin B (CHGB). Plasma NE is substantially heritable (p = 3.19E-16, at 65.2 ± 5.0% of trait variance), sharing significant (p < 0.05) genetic determination with circulating and urinary catecholamines, CHGB, eGFR, and several cardio-metabolic traits. Participants with higher pNE showed significant (p < 0.05) differences in several traits, including increased BP and hypertension risk factors. Peak SGCD variant rs1835919 predicted elevated systemic vascular compliance, without changes in specifically myocardial traits. We used a chimeric-regulated secretory pathway photoprotein (CHGA-EAP) to evaluate the effect of SGCD on the exocytotic pathway in transfected PC12 cells; in transfected cells, expression of SGCD augmented CHGA trafficking into the exocytotic regulated secretory pathway. Thus, our investigation determined human NE secretion to be a highly heritable trait, influenced by common genetic variation within the SGCD locus. Circulating NE aggregates with BP and hypertension risk factors. In addition, coordinate NE and CHGB elevation by rs1835919 implicates exocytosis as the mechanism of release.

  2. Comparative analysis of the within-population genetic structure in wild cherry (Prunus avium L.) at the self-incompatibility locus and nuclear microsatellites.

    PubMed

    Schueler, Silvio; Tusch, Alexandra; Scholz, Florian

    2006-10-01

    Gametophytic self-incompatibility (SI) systems in plants exhibit high polymorphism at the SI controlling S-locus because individuals with rare alleles have a higher probability to successfully pollinate other plants than individuals with more frequent alleles. This process, referred to as frequency-dependent selection, is expected to shape number, frequency distribution, and spatial distribution of self-incompatibility alleles in natural populations. We investigated the genetic diversity and the spatial genetic structure within a Prunus avium population at two contrasting gene loci: nuclear microsatellites and the S-locus. The S-locus revealed a higher diversity (15 alleles) than the eight microsatellites (4-12 alleles). Although the frequency distribution of S-alleles differed significantly from the expected equal distribution, the S-locus showed a higher evenness than the microsatellites (Shannon's evenness index for the S-locus: E = 0.91; for the microsatellites: E = 0.48-0.83). Also, highly significant deviations from neutrality were found for the S-locus whereas only minor deviations were found for two of eight microsatellites. A comparison of the frequency distribution of S-alleles in three age-cohorts revealed no significant differences, suggesting that different levels of selection acting on the S-locus or on S-linked sites might also affect the distribution and dynamics of S-alleles. Autocorrelation analysis revealed a weak but significant spatial genetic structure for the multilocus average of the microsatellites and for the S-locus, but could not ascertain differences in the extent of spatial genetic structure between these locus types. An indirect estimate of gene dispersal, which was obtained to explain this spatial genetic pattern, indicated high levels of gene dispersal within our population (sigma(g) = 106 m). This high gene dispersal, which may be partly due to the self-incompatibility system itself, aids the effective gene flow of the

  3. 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.

  4. A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes

    PubMed Central

    Larsbrink, Johan; Rogers, Theresa E.; Hemsworth, Glyn R.; McKee, Lauren S.; Tauzin, Alexandra S.; Spadiut, Oliver; Klinter, Stefan; Pudlo, Nicholas A.; Urs, Karthik; Koropatkin, Nicole M.; Creagh, A. Louise; Haynes, Charles A.; Kelly, Amelia G.; Cederholm, Stefan Nilsson; Davies, Gideon J.; Martens, Eric C.; Brumer, Harry

    2014-01-01

    A well-balanced human diet includes a significant intake of non-starch polysaccharides, collectively termed “dietary fibre,” from the cell walls of diverse fruits and vegetables.1 Due to a paucity of alimentary enzymes encoded by the human genome,2 our ability to derive energy from dietary fibre depends on saccharification and fermentation of complex carbohydrates by the massive microbial community residing in our distal gut.3,4 The xyloglucans (XyGs), in particular, are a ubiquitous family of highly branched plant cell wall polysaccharides5,6 whose mechanism(s) of degradation in the human gut and consequent importance in nutrition was heretofore unknown.1,7,8 Here, we demonstrate that a single, complex gene locus in Bacteroides ovatus confers xyloglucan catabolism in this common colonic symbiont. Through targeted gene disruption, biochemical analysis of all predicted glycoside hydrolases and carbohydrate-binding proteins, and three-dimensional structural determination of the vanguard endo-xyloglucanase, we reveal the molecular mechanisms through which XyGs are hydrolysed to component monosaccharides for further metabolism. We also observe that orthologous xyloglucan utilization loci (XyGULs) serve as genetic markers of xyloglucan catabolism in Bacteroidetes, that XyGULs are restricted to a limited number of phylogenetically diverse strains, and that XyGULs are ubiquitous in surveyed human metagenomes. Our findings reveal that the metabolism of even highly abundant components of dietary fibre may be mediated by niche species, which has immediate fundamental and practical implications for gut symbiont population ecology in the context of human diet, nutrition and health.9–12 PMID:24463512

  5. Identification of a Genetic Locus in Pseudomonas aureofaciens Involved in Fungal Inhibition

    PubMed Central

    Carruthers, F. L.; Conner, A. J.; Mahanty, H. K.

    1994-01-01

    In iron-rich conditions, Pseudomonas aureofaciens PA147-2 produces an antibiotic-like compound that inhibits the growth of a plant fungal pathogen, Aphanomyces euteiches. To contribute to the potential use of PA147-2 as a biocontrol organism, we report the identification of a genetic locus important for antibiotic biosynthesis. Mutants defective for fungal inhibition (Af-) were generated by Tn5 mutagenesis. Southern hybridization of total DNAs from three Af- mutants indicated that loss of fungal inhibition was due to a single Tn5 insertion in each mutant. Restriction mapping of the mutation points showed that in two mutants the Tn5 insertions were in the same 16.0-kb EcoRI fragment and were separated by 2.1 kb. A genomic library of PA147-2 was constructed and screened by using a region of DNA flanking the Tn5 insertion in one mutant (PA109) as a probe to recover complementing cosmids. Three cosmids containing a 16.0-kb EcoRI fragment complementary to the two mutants were recovered. Allele replacement by homologous recombination with putative complementing cosmids restored one mutant to antifungal activity against A. euteiches. Southern analysis of the complemented mutants confirmed that allele replacement had occurred between cosmid DNA and Tn5. The wild-type 16.0-kb EcoRI fragment was cloned from the cosmid and complemented the two mutants to antifungal activity. An antifungal compound was isolated from PA147-2 grown on solid medium. Antifungal activity correlated to a peak on high-pressure liquid chromatography analysis. Under the same growth and extraction conditions, the antifungal activity seen in PA147-2 was absent in two Af- mutants. Furthermore, absence of an antifungal compound in each mutant correlated to the absence of the wild-type “antifungal” peak on high-pressure liquid chromatography analysis. Images PMID:16349166

  6. A genetic test to determine the origin of maternal transmission ratio distortion. Meiotic drive at the mouse Om locus.

    PubMed Central

    Pardo-Manuel de Villena, F; de la Casa-Esperon, E; Briscoe, T L; Sapienza, C

    2000-01-01

    We have shown previously that the progeny of crosses between heterozygous females and C57BL/6 males show transmission ratio distortion at the Om locus on mouse chromosome 11. This result has been replicated in several independent experiments. Here we show that the distortion maps to a single locus on chromosome 11, closely linked to Om, and that gene conversion is not implicated in the origin of this phenomenon. To further investigate the origin of the transmission ratio distortion we generated a test using the well-known effect of recombination on maternal meiotic drive. The genetic test presented here discriminates between unequal segregation of alleles during meiosis and lethality, based on the analysis of genotype at both the distorted locus and the centromere of the same chromosome. We used this test to determine the cause of the transmission ratio distortion observed at the Om locus. Our results indicate that transmission ratio distortion at Om is due to unequal segregation of alleles to the polar body at the second meiotic division. Because the presence of segregation distortion at Om also depends on the genotype of the sire, our results confirm that the sperm can influence segregation of maternal chromosomes to the second polar body. PMID:10628992

  7. Simple Sequence Repeat and S-locus Genotyping to Explore Genetic Variability in Polyploid Prunus spinosa and P. insititia.

    PubMed

    Halász, Júlia; Makovics-Zsohár, Noémi; Szőke, Ferenc; Ercisli, Sezai; Hegedűs, Attila

    2017-02-01

    Polyploid Prunus spinosa (2n = 4×) and P. insititia (2n = 6×) represent enormous genetic potential in Central Europe, which can be exploited in breeding programmes. In Hungary, 17 cultivar candidates were selected from wild-growing populations including 10 P. spinosa, 4 P. insititia and three P. spinosa × P. domestica hybrids (2n = 5×). Their taxonomic classification was based on their phenotypic characteristics. Six simple sequence repeats (SSRs) and the multiallelic S-locus genotyping were used to characterize genetic variability and reliable identification of the tested accessions. A total of 98 SSR alleles were identified, which presents 19.5 average allele number per locus, and each of the 17 genotypes could be discriminated based on unique SSR fingerprints. A total of 23 S-RNase alleles were identified. The complete and partial S-genotype was determined for 8 and 9 accessions, respectively. The identification of a cross-incompatible pair of cultivar candidates and several semi-compatible combinations help maximize fruit set in commercial orchards. Our results indicate that the S-allele pools of wild-growing P. spinosa and P. insititia are overlapping in Hungary. A phylogenetic and principal component analysis confirmed the high level of diversity and genetic differentiation present within the analysed genotypes and helped clarify doubtful taxonomic identities. Our data confirm that S-locus genotyping is suitable for diversity studies in polyploid Prunus species. The analysed accessions represent huge genetic potential that can be exploited in commercial cultivation.

  8. 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

  9. Approaching the self-incompatibility locus Z in rye (Secale cereale L.) via comparative genetics.

    PubMed

    Hackauf, B; Wehling, P

    2005-03-01

    Using barley and wheat expressed sequence tags as well as rice genomic sequence and mapping information, we revisited the genomic region encompassing the self-incompatibility (SI) locus Z on rye chromosome 2RL applying a comparative approach. We were able to arrange 12 novel sequence-tagged site (STS) markers around Z, spanning a genetic distance of 32.3 cM, with the closest flanking markers mapping at a distance of 0.5 cM and 1.0 cM from Z, respectively, and one marker cosegregating with Z, in a testcross population of 204 progeny. Two overlapping rice bacterial artifical chromosomes (BACs), OSJNBa0070O11 and OSJNBa0010D21, were found to carry rice orthologs of the three rye STS markers from the 1.5-cM interval encompassing Z. The STS-marker orthologs on these rice BACs span less than 125,000 bp of the rice genome. The STS marker TC116908 cosegregated with Z in a mapping population and revealed a high degree of polymorphism among a random sample of rye plants of various origin. TC116908 was shown via Southern hybridization to correspond to gene no. 10 (OSJNBa0070O11.10) on rice BAC OSJNBa0070O11. Reverse transcription-PCR with a TC116908-specific primer pair resulted in the amplification of a fragment of the expected size from the rye pistil but not from leaf cDNA. OSJNBa0070O11.10 was found to show a highly significant sequence similarity to AtUBP22, a ubiquitin-specific protease (UBP). TC116908 likely represents a putative UBP gene that is specifically expressed in rye pistils and cosegregates with Z. Given that the ubiquitination of proteins is emerging as a general mechanism involved in different SI systems of plants, TC116908 appears to be a promising target for further investigation with respect to its relation to the SI system of the grasses.

  10. Molecular genetic diversity and evolution at the MHC DQB locus in four species of pinnipeds.

    PubMed

    Hoelzel, A R; Stephens, J C; O'Brien, S J

    1999-05-01

    Variation was investigated at exon 2 (including part of the putative peptide-binding region) of the class II major histocompatibility complex (MHC) DQB locus for two congeneric phocid seal species and two congeneric otariid seal species. Polymorphism in one phocid species, the southern elephant seal (Mirounga leonina), was comparable to that seen in human populations, while the other phocid, the northern elephant seal (Mirounga angustirostris), has been through a severe population bottleneck and exhibited much less variation at this locus. A phylogenetic comparison of the four species was consistent with the trans-specific pattern of evolution described for other taxa at this locus, and relative nonsynonymous and synonymous substitution rates suggest the maintenance of polymorphisms by natural selection. A comparison of sequence patterns also suggested that some variation could have been generated through recombinational events, primarily within genera. These results suggest a pattern of evolution of the immune response in pinnipeds similar to that in terrestrial mammal species.

  11. A MULTI-LOCUS, MULTI-TAXA PHYLOGEOGRAPHICAL ANALYSIS OF GENETIC DIVERSITY

    EPA Science Inventory

    In addition to measuring spatial patterns of genetic diversity, population genetic measures of biological resources should include temporal data that indicate whether the observed patterns are the result of historical or contemporary processes. In general, genetic measures focus...

  12. Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease.

    PubMed

    Fisher, Sheila A; Tremelling, Mark; Anderson, Carl A; Gwilliam, Rhian; Bumpstead, Suzannah; Prescott, Natalie J; Nimmo, Elaine R; Massey, Dunecan; Berzuini, Carlo; Johnson, Christopher; Barrett, Jeffrey C; Cummings, Fraser R; Drummond, Hazel; Lees, Charlie W; Onnie, Clive M; Hanson, Catherine E; Blaszczyk, Katarzyna; Inouye, Mike; Ewels, Philip; Ravindrarajah, Radhi; Keniry, Andrew; Hunt, Sarah; Carter, Martyn; Watkins, Nick; Ouwehand, Willem; Lewis, Cathryn M; Cardon, Lon; Lobo, Alan; Forbes, Alastair; Sanderson, Jeremy; Jewell, Derek P; Mansfield, John C; Deloukas, Panos; Mathew, Christopher G; Parkes, Miles; Satsangi, Jack

    2008-06-01

    We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.

  13. Genetic and Molecular Characterization of the I Locus of Phaseolus vulgaris

    PubMed Central

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

    2006-01-01

    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

  14. A study on the minimum number of loci required for genetic evaluation using a finite locus model

    PubMed Central

    Totir, Liviu R; Fernando, Rohan L; Dekkers, Jack CM; Fernández, Soledad A

    2004-01-01

    For a finite locus model, Markov chain Monte Carlo (MCMC) methods can be used to estimate the conditional mean of genotypic values given phenotypes, which is also known as the best predictor (BP). When computationally feasible, this type of genetic prediction provides an elegant solution to the problem of genetic evaluation under non-additive inheritance, especially for crossbred data. Successful application of MCMC methods for genetic evaluation using finite locus models depends, among other factors, on the number of loci assumed in the model. The effect of the assumed number of loci on evaluations obtained by BP was investigated using data simulated with about 100 loci. For several small pedigrees, genetic evaluations obtained by best linear prediction (BLP) were compared to genetic evaluations obtained by BP. For BLP evaluation, used here as the standard of comparison, only the first and second moments of the joint distribution of the genotypic and phenotypic values must be known. These moments were calculated from the gene frequencies and genotypic effects used in the simulation model. BP evaluation requires the complete distribution to be known. For each model used for BP evaluation, the gene frequencies and genotypic effects, which completely specify the required distribution, were derived such that the genotypic mean, the additive variance, and the dominance variance were the same as in the simulation model. For lowly heritable traits, evaluations obtained by BP under models with up to three loci closely matched the evaluations obtained by BLP for both purebred and crossbred data. For highly heritable traits, models with up to six loci were needed to match the evaluations obtained by BLP. PMID:15231231

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

    PubMed

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

    2013-08-01

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

  16. Correlation between genetic features of the mef(A)-msr(D) locus and erythromycin resistance in Streptococcus pyogenes.

    PubMed

    Vitali, Luca Agostino; Di Luca, Maria Chiara; Prenna, Manuela; Petrelli, Dezemona

    2016-01-01

    We investigated the correlation between the genetic variation within mef(A)-msr(D) determinants of efflux-mediated erythromycin resistance in Streptococcus pyogenes and the level of erythromycin resistance. Twenty-eight mef(A)-positive strains were selected according to erythromycin MIC (4-32 μg/mL), and their mef(A)-msr(D) regions were sequenced. Strains were classified according to the bacteriophage carrying mef(A)-msr(D). A new Φm46.1 genetic variant was found in 8 strains out of 28 and named VP_00501.1. Degree of allelic variation was higher in mef(A) than in msr(D). Hotspots for recombination were mapped within the locus that could have shaped the apparent mosaic structure of the region. There was a general correlation between mef(A)-msr(D) sequence and erythromycin resistance level. However, lysogenic conversion of susceptible strains by mef(A)-msr(D)-carrying Φm46.1 indicated that key determinants may not all reside within the mef(A)-msr(D) locus and that horizontal gene transfer could contribute to changes in the level of antibiotic resistance in S. pyogenes.

  17. Loss of genetic diversity at an MHC locus in the endangered Tokyo bitterling Tanakia tanago (Teleostei: Cyprinidae).

    PubMed

    Kubota, Hitoshi; Watanabe, Katsutoshi

    2013-12-01

    Genetic diversity at a major histocompatibility complex (MHC) class II B gene was examined for two wild and three captive populations of the endangered Tokyo bitterling Tanakia tanago. A specific primer set was first developed to amplify the MHC II B exon 2 locus. Using single strand conformation polymorphism (SSCP) and sequencing analysis, 16 DAB3 alleles were detected with 56 nucleotide substitutions in the 276-bp region. In the putative antigen-binding sites of exon 2, the rate of nonsynonymous substitutions was significantly higher than that of synonymous substitutions (dN/dS = 2.79), indicating positive selection on the retention of polymorphism. The population from the Handa Natural Habitat Conservation Area and that from the Tone River system exhibited low variation (one and three alleles, respectively), whereas the captive population that originated from a mix of three distinct populations had the highest amounts of variation (14 alleles). The levels of heterozygosity at the MHC varied considerably among populations and showed significant correlations with those at putative neutral microsatellite markers, suggesting that genetic drift following a bottleneck has affected MHC variability in some populations. Comparisons between endangered and non-endangered fish species in previous reports and the present results indicate that the number of MHC alleles per population is on average 70% lower in endangered species than non-endangered species. Considering the functional consequence of this locus, attention should be paid to captive and wild endangered fish populations in terms of further loss of MHC alleles.

  18. Molecular and genetic analyses of the putative Proteus O antigen gene locus.

    PubMed

    Wang, Quan; Torzewska, Agnieszka; Ruan, Xiaojuan; Wang, Xiaoting; Rozalski, Antoni; Shao, Zhujun; Guo, Xi; Zhou, Haijian; Feng, Lu; Wang, Lei

    2010-08-01

    Proteus species are well-characterized opportunistic pathogens primarily associated with urinary tract infections (UTI) of humans. The Proteus O antigen is one of the most variable constituents of the cell surface, and O antigen heterogeneity is used for serological classification of Proteus isolates. Even though most Proteus O antigen structures have been identified, the O antigen locus has not been well characterized. In this study, we identified the putative Proteus O antigen locus and demonstrated this region's high degree of heterogeneity by comparing sequences of 40 Proteus isolates using PCR-restriction fragment length polymorphism (RFLP). This analysis identified five putative Proteus O antigen gene clusters, and the probable functions of these O antigen-related genes were proposed, based on their similarity to genes in the available databases. Finally, Proteus-specific genes from these five serogroups were identified by screening 79 strains belonging to the 68 Proteus O antigen serogroups. To our knowledge, this is the first molecular characterization of the putative Proteus O antigen locus, and we describe a novel molecular classification method for the identification of different Proteus serogroups.

  19. Genetic and molecular characterization of the maize rp3 rust resistance locus.

    PubMed Central

    Webb, Craig A; Richter, Todd E; Collins, Nicholas C; Nicolas, Marie; Trick, Harold N; Pryor, Tony; Hulbert, Scot H

    2002-01-01

    In maize, the Rp3 gene confers resistance to common rust caused by Puccinia sorghi. Flanking marker analysis of rust-susceptible rp3 variants suggested that most of them arose via unequal crossing over, indicating that rp3 is a complex locus like rp1. The PIC13 probe identifies a nucleotide binding site-leucine-rich repeat (NBS-LRR) gene family that maps to the complex. Rp3 variants show losses of PIC13 family members relative to the resistant parents when probed with PIC13, indicating that the Rp3 gene is a member of this family. Gel blots and sequence analysis suggest that at least 9 family members are at the locus in most Rp3-carrying lines and that at least 5 of these are transcribed in the Rp3-A haplotype. The coding regions of 14 family members, isolated from three different Rp3-carrying haplotypes, had DNA sequence identities from 93 to 99%. Partial sequencing of clones of a BAC contig spanning the rp3 locus in the maize inbred line B73 identified five different PIC13 paralogues in a region of approximately 140 kb. PMID:12242248

  20. Unravelling the Molecular Epidemiology and Genetic Diversity among Burkholderia pseudomallei Isolates from South India Using Multi-Locus Sequence Typing

    PubMed Central

    Shaw, Tushar; KE, Vandana; Kumar, Subodh; Bhat, Vinod; Mukhopadhyay, Chiranjay

    2016-01-01

    There is a slow but steady rise in the case detection rates of melioidosis from various parts of the Indian sub-continent in the past two decades. However, the epidemiology of the disease in India and the surrounding South Asian countries remains far from well elucidated. Multi-locus sequence typing (MLST) is a useful epidemiological tool to study the genetic relatedness of bacterial isolates both with-in and across the countries. With this background, we studied the molecular epidemiology of 32 Burkholderia pseudomallei isolates (31 clinical and 1 soil isolate) obtained during 2006–2015 from various parts of south India using multi-locus sequencing typing and analysis. Of the 32 isolates included in the analysis, 30 (93.7%) had novel allelic profiles that were not reported previously. Sequence type (ST) 1368 (n = 15, 46.8%) with allelic profile (1, 4, 6, 4, 1, 1, 3) was the most common genotype observed. We did not observe a genotypic association of STs with geographical location, type of infection and year of isolation in the present study. Measure of genetic differentiation (FST) between Indian and the rest of world isolates was 0.14413. Occurrence of the same ST across three adjacent states of south India suggest the dispersion of B.pseudomallei across the south western coastal part of India with limited geographical clustering. However, majority of the STs reported from the present study remained as “outliers” on the eBURST “Population snapshot”, suggesting the genetic diversity of Indian isolates from the Australasian and Southeast Asian isolates. PMID:27992477

  1. Identification of a genetic locus controlling bacteria-driven colitis and associated cancer through effects on innate inflammation

    PubMed Central

    Boulard, Olivier; Kirchberger, Stefanie; Royston, Daniel J.; Maloy, Kevin J.

    2012-01-01

    Chronic inflammation of the intestine has been associated with an elevated risk of developing colorectal cancer. Recent association studies have highlighted the role of genetic predisposition in the etiology of colitis and started to unravel its complexity. However, the genetic factors influencing the progression from colon inflammation to tumorigenesis are not known. We report the identification of a genetic interval Hiccs that regulates Helicobacter hepaticus–induced colitis and associated cancer susceptibility in a 129.RAG−/− mouse model. The 1.7-Mb congenic interval on chromosome 3, containing eight genes and five microRNAs, renders susceptible mice resistant to colitis and reduces tumor incidence and multiplicity. Bone marrow chimera experiments showed that resistance is conferred by the hematopoietic compartment. Moreover, the Hiccs locus controls the induction of the innate inflammatory response by regulating cytokine expression and granulocyte recruitment by Thy1+ innate lymphoid cells. Using a tumor-promoting model combining chronic Helicobacter hepaticus infection and the carcinogen azoxymethane, we found that Hiccs also regulates the frequency of colitis-associated neoplasia. Our study highlights the importance of innate immune cells and their genetic configuration in driving progression from inflammation toward cancer and opens the door for analysis of these pathways in human inflammatory disorders and associated cancers. PMID:22734048

  2. Molecular genetics of the brown (b)-locus region of mouse chromosome 4. II. Complementation analyses of lethal brown deletions.

    PubMed

    Rinchik, E M

    1994-07-01

    Numerous new mutations at the brown (b) locus in mouse chromosome 4 have been recovered over the years in germ-cell mutagenesis experiments performed at the Oak Ridge National Laboratory. A large series of radiation- and chemical-induced b mutations known to be chromosomal deletions, and also known to be prenatally lethal when homozygous, were analyzed by pairwise complementation crosses as well as by pseudodominance tests involving flanking loci defined by externally visible phenotypes. These crosses were designed to determine the extent of each deletion on the genetic and phenotype map of the chromosomal region surrounding the b locus; the crosses also provided basic data that assigned deletions to complementation groups and defined four new loci associated with aberrancies in normal development. Specifically, the pseudodominance tests identified deletions that include the proximally mapping whirler (wi) and the distally mapping depilated (dep) genes, thereby bracketing these loci defined by visible developmental abnormalities with landmarks (deletion breakpoints) that are easily identified on the physical map. Furthermore, the complementation crosses, which were supplemented with additional crosses that allowed determination of the gross time of lethality of selected deletions, defined four new loci required for normal development. Homozygous deletion of one of these loci (b-associated fitness, baf) results in a runting syndrome evident during postnatal development; deletion of one locus [l(4)2Rn] causes death in the late gestation/neonatal period; and deletion of either of two loci [l(4)1Rn or l(4)3Rn] results in embryonic death, most likely in pre-, peri- or postimplantation stages. The placement of these new functionally defined loci on the evolving molecular map of the b region should be useful for continuing the analysis of the roles played in development by genes in this segment of chromosome 4.

  3. Assessment of population genetic structure in the arbovirus vector midge, Culicoides brevitarsis (Diptera: Ceratopogonidae), using multi-locus DNA microsatellites.

    PubMed

    Onyango, Maria G; Beebe, Nigel W; Gopurenko, David; Bellis, Glenn; Nicholas, Adrian; Ogugo, Moses; Djikeng, Appolinaire; Kemp, Steve; Walker, Peter J; Duchemin, Jean-Bernard

    2015-09-25

    Bluetongue virus (BTV) is a major pathogen of ruminants that is transmitted by biting midges (Culicoides spp.). Australian BTV serotypes have origins in Asia and are distributed across the continent into two distinct episystems, one in the north and another in the east. Culicoides brevitarsis is the major vector of BTV in Australia and is distributed across the entire geographic range of the virus. Here, we describe the isolation and use of DNA microsatellites and gauge their ability to determine population genetic connectivity of C. brevitarsis within Australia and with countries to the north. Eleven DNA microsatellite markers were isolated using a novel genomic enrichment method and identified as useful for genetic analyses of sampled populations in Australia, northern Papua New Guinea (PNG) and Timor-Leste. Significant (P < 0.05) population genetic subdivision was observed between all paired regions, though the highest levels of genetic sub-division involved pair-wise tests with PNG (PNG vs. Australia (FST = 0.120) and PNG vs. Timor-Leste (FST = 0.095)). Analysis of multi-locus allelic distributions using STRUCTURE identified a most probable two-cluster population model, which separated PNG specimens from a cluster containing specimens from Timor-Leste and Australia. The source of incursions of this species in Australia is more likely to be Timor-Leste than PNG. Future incursions of BTV positive C. brevitarsis into Australia may be genetically identified to their source populations using these microsatellite loci. The vector's panmictic genetic structure within Australia cannot explain the differential geographic distribution of BTV serotypes.

  4. Genetic instability of the lozenge locus in Drosophila melanogaster: Characterization of the lz{sup 75V} allele

    SciTech Connect

    Voloshina, M.A.; Golubovskii, M.D.

    1995-12-01

    Genetic properties of lz{sup 75V}, an unstable allele of the lozenge locus, are described. The lz{sup 75V} allele appeared in progeny of a male from a Far East natural population of Drosophila melanogaster. Mutation of this allele produces a broad spectrum of mutant derivatives with phenotypes varying from normal to extreme. The arising alleles can be stable or unstable. Some lz{sup 75V} derivatives continuously preserve their spontaneous mutability in laboratory conditions, whereas other alleles of the same family show progressive stabilization at the intralocus or intrachromosome level. Instability of the lz{sup 75V}-bearing X chromosome is locus-specific: only the lozenge gene mutates with high frequency, while visible mutations at other loci rarely occur. As shown previously, the lz{sup 75V} allele appears to be caused by a P-element insertion. The appearance of spontaneous instability is discussed with regard to the general problem of transposition regulation in mobile elements. Different systems of hybrid dysgenesis, and, in particular, P elements are assumed to play an important role in induction of unstable mutations in nature. 24 refs., 5 tabs.

  5. 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.

  6. The Multi-allelic Genetic Architecture of a Variance-Heterogeneity Locus for Molybdenum Concentration in Leaves Acts as a Source of Unexplained Additive Genetic Variance

    PubMed Central

    Forsberg, Simon K. G.; Andreatta, Matthew E.; Huang, Xin-Yuan; Danku, John; Salt, David E.; Carlborg, Örjan

    2015-01-01

    Genome-wide association (GWA) analyses have generally been used to detect individual loci contributing to the phenotypic diversity in a population by the effects of these loci on the trait mean. More rarely, loci have also been detected based on variance differences between genotypes. Several hypotheses have been proposed to explain the possible genetic mechanisms leading to such variance signals. However, little is known about what causes these signals, or whether this genetic variance-heterogeneity reflects mechanisms of importance in natural populations. Previously, we identified a variance-heterogeneity GWA (vGWA) signal for leaf molybdenum concentrations in Arabidopsis thaliana. Here, fine-mapping of this association reveals that the vGWA emerges from the effects of three independent genetic polymorphisms that all are in strong LD with the markers displaying the genetic variance-heterogeneity. By revealing the genetic architecture underlying this vGWA signal, we uncovered the molecular source of a significant amount of hidden additive genetic variation or “missing heritability”. Two of the three polymorphisms underlying the genetic variance-heterogeneity are promoter variants for Molybdate transporter 1 (MOT1), and the third a variant located ~25 kb downstream of this gene. A fourth independent association was also detected ~600 kb upstream of MOT1. Use of a T-DNA knockout allele highlights Copper Transporter 6; COPT6 (AT2G26975) as a strong candidate gene for this association. Our results show that an extended LD across a complex locus including multiple functional alleles can lead to a variance-heterogeneity between genotypes in natural populations. Further, they provide novel insights into the genetic regulation of ion homeostasis in A. thaliana, and empirically confirm that variance-heterogeneity based GWA methods are a valuable tool to detect novel associations of biological importance in natural populations. PMID:26599497

  7. Data on genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice.

    PubMed

    Grainger, Andrew T; Jones, Michael B; Li, Jing; Chen, Mei-Hua; Manichaikul, Ani; Shi, Weibin

    2016-12-01

    The data presented here are related to the research article, entitled Genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice, published in Atherosclerosis 2016;254:124 (A.T. Grainger, M.B. Jones, J. Li, M.H. Chen, A. Manichaikul, W. Shi, 2016) [1]. The supporting materials include original genotypic and phenotypic data obtained from 206 female F2 mice derived from an intercross between BALB and SMJ inbred mice. The F2 mice were fed 12 weeks of Western diet, starting at 6 weeks of age. Atherosclerotic lesion size in the aortic root of each mouse is the sum of the top 8 lesion areas. The data is provided in the format required for determining QTLs using two independent programs, J/QTL and PLINK.

  8. 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.

  9. 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

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

    PubMed

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

    2016-11-21

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

  11. Genetic relationship between lodging and lodging components in barley (Hordeum vulgare) based on unconditional and conditional quantitative trait locus analyses.

    PubMed

    Chen, W Y; Liu, Z M; Deng, G B; Pan, Z F; Liang, J J; Zeng, X Q; Tashi, N M; Long, H; Yu, M Q

    2014-03-17

    Lodging (LD) is a major constraint limiting the yield and forage quality of barley. Detailed analyses of LD component (LDC) traits were conducted using 246 F2 plants generated from a cross between cultivars ZQ320 and 1277. Genetic relationships between LD and LDC were evaluated by unconditional and conditional quantitative trait locus (QTL) mapping with 117 simple sequence repeat markers. Ultimately, 53 unconditional QTL related to LD were identified on seven barley chromosomes. Up to 15 QTL accounted for over 10% of the phenotypic variation, and up to 20 QTL for culm strength were detected. Six QTL with pleiotropic effects showing significant negative correlations with LD were found between markers Bmag353 and GBM1482 on chromosome 4H. These alleles and alleles of QTL for wall thickness, culm strength, plant height, and plant weight originated from ZQ320. Conditional mapping identified 96 additional QTL for LD. Conditional QTL analysis demonstrated that plant height, plant height center of gravity, and length of the sixth internode had the greatest contribution to LD, whereas culm strength and length of the fourth internode, and culm strength of the second internode were the key factors for LD-resistant. Therefore, lodging resistance in barley can be improved based on selection of alleles affecting culm strength, wall thickness, plant height, and plant weight. The conditional QTL mapping method can be used to evaluate possible genetic relationships between LD and LDC while efficiently and precisely determining counteracting QTL, which will help in understanding the genetic basis of LD in barley.

  12. Genetic Control of Pheromones in Drosophila Simulans. II. Kete, a Locus on the X Chromosome

    PubMed Central

    Ferveur, J. F.; Jallon, J. M.

    1993-01-01

    The production of Drosophila cuticular hydrocarbons, including contact pheromones, is under polygenic control. To investigate X-linked loci, EMS mutations were induced in Drosophila simulans flies. A mutant strain was discovered which in both sexes show a reduction in the biosynthesis of both 7-tricosene (7-T) the species contact pheromone and all other linear hydrocarbons. The locus controlling this effect, kete, is recessive and was localized to I, 18.5. Unlike a previously identified gene on the second chromosome of this species, Ngbo, kete does not affect the ratio of 7-T:7-pentacosene (7-P). Other reproductive characteristics are also affected, including egg-hatching. However, courtship behaviors in both sexes appear normal. PMID:8454203

  13. Genetic diversity of the class II major histocompatibility DRA locus in European, Asiatic and African domestic donkeys.

    PubMed

    Vranova, Marie; Alloggio, Ingrid; Qablan, Moneeb; Vyskocil, Mirko; Baumeisterova, Aneta; Sloboda, Michal; Putnova, Lenka; Vrtkova, Irena; Modry, David; Horin, Petr

    2011-07-01

    The major histocompatibility complex (MHC) genes coding for antigen presenting molecules are the most polymorphic genes in vertebrate genome. The MHC class II DRA gene shows only small variation in many mammalian species, but it exhibits relatively high level of polymorphism in Equidae, especially in donkeys. This extraordinary degree of polymorphism together with signatures of selection in specific amino acids sites makes the donkey DRA gene a suitable model for population diversity studies. The objective of this study was to investigate the DRA gene diversity in three different populations of donkeys under infectious pressure of protozoan parasites, Theileria equi and Babesia caballi. Three populations of domestic donkeys from Italy (N = 68), Jordan (N = 43), and Kenya (N = 78) were studied. A method of the donkey MHC DRA genotyping based on PCR-RFLP and sequencing was designed. In addition to the DRA gene, 12 polymorphic microsatellite loci were genotyped. The presence of Theileria equi and Babesia caballi parasites in peripheral blood was investigated by PCR. Allele and genotype frequencies, observed and expected heterozygosities and F(IS) values were computed as parameters of genetic diversity for all loci genotyped. Genetic distances between the three populations were estimated based on F(ST) values. Statistical associations between parasite infection and genetic polymorphisms were sought. Extensive DRA locus variation characteristic for Equids was found. The results showed differences between populations both in terms of numbers of alleles and their frequencies as well as variation in expected heterozygosity values. Based on comparisons with neutral microsatellite loci, population sub-structure characteristics and association analysis, convincing evidence of pathogen-driven selection at the population level was not provided. It seems that genetic diversity observed in the three populations reflects mostly effects of selective breeding and their different

  14. Distinguishing the Forces Controlling Genetic Variation at the Xdh Locus in Drosophila Pseudoobscura

    PubMed Central

    Riley, M. A.; Hallas, M. E.; Lewontin, R. C.

    1989-01-01

    Fifty-eight isochromosomal lines sampled from two natural populations of Drosophila pseudoobscura in California and one from Bogota, Colombia, were examined using four-cutter restriction mapping. A 4.6-kb region of the xanthine dehydrogenase locus was probed and 66 of 135 restriction sites scored were polymorphic. This predicts that on average every 12th bp would be polymorphic in this region for the genes surveyed if polymorphism occurred randomly along the coding region. In addition, there were 12 insertion/deletion polymorphisms. Forty-nine distinct haplotypes were recognized in the 58 lines examined. The most common haplotype obtained a frequency of only 5%. Measures of base pair heterozygosity (0.0097) and linkage disequilibrium lead to a predicted population size in the range of 1.2-2.4 X 10(6) for the species. High levels of recombination (including gene conversion) can be inferred from the presence of all four gametic types in the data set. PMID:2583480

  15. Dynamics of Genetic Variability in Two-Locus Models of Stabilizing Selection

    PubMed Central

    Gavrilets, S.; Hastings, A.

    1994-01-01

    We study a two locus model, with additive contributions to the phenotype, to explore the dynamics of different phenotypic characteristics under stabilizing selection and recombination. We demonstrate that the interaction of selection and recombination results in constraints on the mode of phenotypic evolution. Let V(g) be the genic variance of the trait and C(L) be the contribution of linkage disequilibrium to the genotypic variance. We demonstrate that, independent of the initial conditions, the dynamics of the system on the plane (V(g), C(L)) are typically characterized by a quick approach to a straight line with slow evolution along this line afterward. We analyze how the mode and the rate of phenotypic evolution depend on the strength of selection relative to recombination, on the form of fitness function, and the difference in allelic effect. We argue that if selection is not extremely weak relative to recombination, linkage disequilibrium generated by stabilizing selection influences the dynamics significantly. We demonstrate that under these conditions, which are plausible in nature and certainly the case in artificial stabilizing selection experiments, the model can have a polymorphic equilibrium with positive linkage disequilibrium that is stable simultaneously with monomorphic equilibria. PMID:7828833

  16. 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.

  17. Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma.

    PubMed

    Jannot, Anne-Sophie; Meziani, Roubila; Bertrand, Guylene; Gérard, Benedicte; Descamps, Vincent; Archimbaud, Alain; Picard, Catherine; Ollivaud, Laurence; Basset-Seguin, Nicole; Kerob, Delphine; Lanternier, Guy; Lebbe, Celeste; Saiag, P; Crickx, Beatrice; Clerget-Darpoux, Françoise; Grandchamp, Bernard; Soufir, Nadem; Melan-Cohort

    2005-08-01

    The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma.

  18. Genetic architecture of growth traits in Populus revealed by integrated quantitative trait locus (QTL) analysis and association studies.

    PubMed

    Du, Qingzhang; Gong, Chenrui; Wang, Qingshi; Zhou, Daling; Yang, Haijiao; Pan, Wei; Li, Bailian; Zhang, Deqiang

    2016-02-01

    Deciphering the genetic architecture underlying polygenic traits in perennial species can inform molecular marker-assisted breeding. Recent advances in high-throughput sequencing have enabled strategies that integrate linkage-linkage disequilibrium (LD) mapping in Populus. We used an integrated method of quantitative trait locus (QTL) dissection with a high-resolution linkage map and multi-gene association mapping to decipher the nature of genetic architecture (additive, dominant, and epistatic effects) of potential QTLs for growth traits in a Populus linkage population (1200 progeny) and a natural population (435 individuals). Seventeen QTLs for tree height, diameter at breast height, and stem volume mapped to 11 linkage groups (logarithm of odds (LOD) ≥ 2.5), and explained 2.7-18.5% of the phenotypic variance. After comparative mapping and transcriptome analysis, 187 expressed genes (10 046 common single nucleotide polymorphisms (SNPs)) were selected from the segmental homology regions (SHRs) of 13 QTLs. Using multi-gene association models, we observed 202 significant SNPs in 63 promising genes from 10 QTLs (P ≤ 0.0001; FDR ≤ 0.10) that exhibited reproducible associations with additive/dominant effects, and further determined 11 top-ranked genes tightly linked to the QTLs. Epistasis analysis uncovered a uniquely interconnected gene-gene network for each trait. This study opens up opportunities to uncover the causal networks of interacting genes in plants using an integrated linkage-LD mapping approach.

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

    SciTech Connect

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

    1994-09-01

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

  20. Genetic analysis of a novel plasmid encoded durancin locus in Enterococcus durans 41D

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enterococcus durans is commonly found in the intestinal tract in humans and animals and several strains are known to produce bacteriocins. Durancin GL, a novel bacteriocin of Enterococcus durans 41D with antilisterial activity was isolated from artisanal cheese samples and its genetic determinants ...

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

    PubMed Central

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

    2017-01-01

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

  2. The sil Locus in Streptococcus Anginosus Group: Interspecies Competition and a Hotspot of Genetic Diversity

    PubMed Central

    Mendonca, Michelle L.; Szamosi, Jake C.; Lacroix, Anne-Marie; Fontes, Michelle E.; Bowdish, Dawn M.; Surette, Michael G.

    2017-01-01

    The Streptococcus Invasion Locus (Sil) was first described in Streptococcus pyogenes and Streptococcus pneumoniae, where it has been implicated in virulence. The two-component peptide signaling system consists of the SilA response regulator and SilB histidine kinase along with the SilCR signaling peptide and SilD/E export/processing proteins. The presence of an associated bacteriocin region suggests this system may play a role in competitive interactions with other microbes. Comparative analysis of 42 Streptococcus Anginosus/Milleri Group (SAG) genomes reveals this to be a hot spot for genomic variability. A cluster of bacteriocin/immunity genes is found adjacent to the sil system in most SAG isolates (typically 6–10 per strain). In addition, there were two distinct SilCR peptides identified in this group, denoted here as SilCRSAG-A and SilCRSAG-B, with corresponding alleles in silB. Our analysis of the 42 sil loci showed that SilCRSAG-A is only found in Streptococcus intermedius while all three species can carry SilCRSAG-B. In S. intermedius B196, a putative SilA operator is located upstream of bacteriocin gene clusters, implicating the sil system in regulation of microbe–microbe interactions at mucosal surfaces where the group resides. We demonstrate that S. intermedius B196 responds to its cognate SilCRSAG-A, and, less effectively, to SilCRSAG-B released by other Anginosus group members, to produce putative bacteriocins and inhibit the growth of a sensitive strain of S. constellatus. PMID:28119678

  3. The sil Locus in Streptococcus Anginosus Group: Interspecies Competition and a Hotspot of Genetic Diversity.

    PubMed

    Mendonca, Michelle L; Szamosi, Jake C; Lacroix, Anne-Marie; Fontes, Michelle E; Bowdish, Dawn M; Surette, Michael G

    2016-01-01

    The Streptococcus Invasion Locus (Sil) was first described in Streptococcus pyogenes and Streptococcus pneumoniae, where it has been implicated in virulence. The two-component peptide signaling system consists of the SilA response regulator and SilB histidine kinase along with the SilCR signaling peptide and SilD/E export/processing proteins. The presence of an associated bacteriocin region suggests this system may play a role in competitive interactions with other microbes. Comparative analysis of 42 Streptococcus Anginosus/Milleri Group (SAG) genomes reveals this to be a hot spot for genomic variability. A cluster of bacteriocin/immunity genes is found adjacent to the sil system in most SAG isolates (typically 6-10 per strain). In addition, there were two distinct SilCR peptides identified in this group, denoted here as SilCRSAG-A and SilCRSAG-B, with corresponding alleles in silB. Our analysis of the 42 sil loci showed that SilCRSAG-A is only found in Streptococcus intermedius while all three species can carry SilCRSAG-B. In S. intermedius B196, a putative SilA operator is located upstream of bacteriocin gene clusters, implicating the sil system in regulation of microbe-microbe interactions at mucosal surfaces where the group resides. We demonstrate that S. intermedius B196 responds to its cognate SilCRSAG-A, and, less effectively, to SilCRSAG-B released by other Anginosus group members, to produce putative bacteriocins and inhibit the growth of a sensitive strain of S. constellatus.

  4. 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.

  5. Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae) cultivars.

    PubMed

    Shahin, Arwa; Smulders, Marinus J M; van Tuyl, Jaap M; Arens, Paul; Bakker, Freek T

    2014-01-01

    Next Generation Sequencing (NGS) may enable estimating relationships among genotypes using allelic variation of multiple nuclear genes simultaneously. We explored the potential and caveats of this strategy in four genetically distant Lilium cultivars to estimate their genetic divergence from transcriptome sequences using three approaches: POFAD (Phylogeny of Organisms from Allelic Data, uses allelic information of sequence data), RAxML (Randomized Accelerated Maximum Likelihood, tree building based on concatenated consensus sequences) and Consensus Network (constructing a network summarizing among gene tree conflicts). Twenty six gene contigs were chosen based on the presence of orthologous sequences in all cultivars, seven of which also had an orthologous sequence in Tulipa, used as out-group. The three approaches generated the same topology. Although the resolution offered by these approaches is high, in this case there was no extra benefit in using allelic information. We conclude that these 26 genes can be widely applied to construct a species tree for the genus Lilium.

  6. Multi-Locus Phylogeographic and Population Genetic Analysis of Anolis carolinensis: Historical Demography of a Genomic Model Species

    PubMed Central

    Tollis, Marc; Ausubel, Gavriel; Ghimire, Dhruba; Boissinot, Stéphane

    2012-01-01

    The green anole (Anolis carolinensis) has been widely used as an animal model in physiology and neurobiology but has recently emerged as an important genomic model. The recent sequencing of its genome has shed new light on the evolution of vertebrate genomes and on the process that govern species diversification. Surprisingly, the patterns of genetic diversity within natural populations of this widespread and abundant North American lizard remain relatively unknown. In the present study, we use 10 novel nuclear DNA sequence loci (N = 62 to 152) and one mitochondrial locus (N = 226) to delimit green anole populations and infer their historical demography. We uncovered four evolutionarily distinct and geographically restricted lineages of green anoles using phylogenetics, Bayesian clustering, and genetic distance methods. Molecular dating indicates that these lineages last shared a common ancestor ∼2 million years ago. Summary statistics and analysis of the frequency distributions of DNA polymorphisms strongly suggest range-wide expansions in population size. Using Bayesian Skyline Plots, we inferred the timing of population size expansions, which differ across lineages, and found evidence for a relatively recent and rapid westward expansion of green anoles across the Gulf Coastal Plain during the mid-Pleistocene. One surprising result is that the distribution of genetic diversity is not consistent with a latitudinal shift caused by climatic oscillations as is observed for many co-distributed taxa. This suggests that the most recent Pleistocene glacial cycles had a limited impact on the geographic distribution of the green anole at the northern limits of its range. PMID:22685573

  7. 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.

  8. 75 FR 52949 - Notice of Meeting: Secretary's Advisory Committee on Genetics, Health, and Society

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ... Genetics, Health, and Society Pursuant to Public Law 92-463, notice is hereby given of the twenty-third meeting of the Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS), U.S. Public... cast. The main agenda item will be a review of the revised draft report on genetics education...

  9. 75 FR 52949 - Notice of Meeting: Secretary's Advisory Committee on Genetics, Health, and Society

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ... HUMAN SERVICES Office of the Secretary Notice of Meeting: Secretary's Advisory Committee on Genetics... the Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS), U.S. Public Health... cast. The main agenda item will be a review of the revised draft report on genetics education...

  10. 75 FR 21295 - Notice of Meeting: Secretary's Advisory Committee on Genetics, Health, and Society

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... HUMAN SERVICES Office of the Secretary Notice of Meeting: Secretary's Advisory Committee on Genetics... the Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS), U.S. Public Health... wishing to provide public comment on any issue related to genetics, health and society. Please note...

  11. 75 FR 21002 - Notice of Meeting: Secretary's Advisory Committee on Genetics, Health, and Society

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-22

    ... Genetics, Health, and Society Pursuant to Public Law 92-463, notice is hereby given of the twenty-second meeting of the Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS), U.S. Public... wishing to provide public comment on any issue related to genetics, health and society. Please note...

  12. Historical gene flow and profound spatial genetic structure among golden pheasant populations suggested by multi-locus analysis.

    PubMed

    He, Ke; Liu, Hong-Yi; Ge, Yun-Fa; Wu, Shao-Ying; Wan, Qiu-Hong

    2017-05-01

    Major histocompatibility complex (MHC) is a good marker system for geographical genetics since they are functional genes in the immune system that are likely to affect the fitness of the individual, and the survival and evolutionary potential of a population in a changing environment. Golden pheasant (Chrysolophus pictus) is a wild Phasianidae distributed in central and north China. In this study, we used a locus-specific genotyping technique for MHC IIB genes of golden pheasant. Combining with microsatellites (simple sequence repeat, SSR) and mitochondrial DNA (mtDNA) D-loop region, we investigated the demographic history and illuminate genetic structure of this bird in detail. SYR (south of Yangtze river) - NYR (north of Yangtze river) lineages, separated by Yangtze River, were defined in genetic structure of MHC IIB. NYR was supposed as refuge during glacial period, suggested by diversity parameters and more ancient alleles in this region. Based on this hypothesis, there was gene flow from NYR to SYR, which was proved by three pieces of evidence: (1) distinct demographic histories of SYR (kept stable) and NYR (experienced expansion); (2) specific affiliation of LC in genetic structure of SSR and MHC genes; (3) significant gene flow from NYR to SYR. Moreover, we also found balancing selection by combination of three Grouping A2's regions (SC, QL and North) into one in Grouping B4 (NYR) and no pattern of isolation by distance (IBD) found in MHC IIB, whereas for SSR we found a relatively strong and significant IBD. Several mechanisms in the evolution of MHC IIB genes, including recombination, historically positive selection, trans-species evolution and concerted evolution, were shown by molecular and phylogenetic analysis. Overall these results suggest the Yangtze River was inferred to be a geological barrier for this avian and NYR might experience population expansion, which invaded into a neighboring region. This study contributes to the understanding of the

  13. Link functions in multi-locus genetic models: implications for testing, prediction, and interpretation.

    PubMed

    Clayton, David

    2012-05-01

    "Complex" diseases are, by definition, influenced by multiple causes, both genetic and environmental, and statistical work on the joint action of multiple risk factors has, for more than 40 years, been dominated by the generalized linear model (GLM). In genetics, models for dichotomous traits have traditionally been approached via the model of an underlying, normally distributed, liability. This corresponds to the GLM with binomial errors and a probit link function. Elsewhere in epidemiology, however, the logistic regression model, a GLM with logit link function, has been the tool of choice, largely because of its convenient properties in case-control studies. The choice of link function has usually been dictated by mathematical convenience, but it has some important implications in (a) the choice of association test statistic in the presence of existing strong risk factors, (b) the ability to predict disease from genotype given its heritability, and (c) the definition, and interpretation of epistasis (or epistacy). These issues are reviewed, and a new association test proposed.

  14. Multi-locus genetic risk score predicts risk for Crohn’s disease in Slovenian population

    PubMed Central

    Zupančič, Katarina; Skok, Kristijan; Repnik, Katja; Weersma, Rinse K; Potočnik, Uroš; Skok, Pavel

    2016-01-01

    AIM: To develop a risk model for Crohn’s disease (CD) based on homogeneous population. METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms (SNPs). We generated genetic risk scores (GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve (AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios (LR) of a test, with LR > 5 for high risk group and LR < 0.20 for low risk group. RESULTS: The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk (GRS > 5.54) showed significantly increased odds of developing CD (OR = 26.65, 95%CI: 11.25-63.15) compared to the individuals with the lowest risk (GRS < 4.57) which is a considerably greater risk captured than in one SNP with the highest effect size (OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76. CONCLUSION: The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population. PMID:27076762

  15. The genetic basis of Muir-Torre syndrome includes the hMLH1 locus

    SciTech Connect

    Bapat, B.; Xia, L.; Mitri, A.

    1996-09-01

    Muir-Torre syndrome (MTS) (McKusick 158320) is an autosomal dominant disorder characterized by the development of sebaceous gland tumors and skin cancers, including keratoacanthomas and basal cell carcinomas. Affected family members may manifest a wide spectrum of internal malignancies, which include colorectal, endometrial, urologic, and upper gastrointestinal neoplasms. Sebaceous gland tumors, which are rare in the general population, are considered to be the hallmark of MTS and may arise prior to the development of other visceral cancers. Despite the high incidence of synchronous and metachronous tumors, prognosis is often favorable. Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common autosomal dominantly inherited colorectal cancer susceptibility syndromes. In some HNPCC families, extracolonic tumors of the endometrium, ovary, small bowel, and renal and biliary tract occur at an increased frequency. On the basis of similarities in clinical symptoms of MTS and HNPCC, it is proposed that these two syndromes may have a common genetic basis. 24 refs., 2 figs.

  16. Genetic locus on chromosome 6p for multicystic renal dysplasia, pelvi-ureteral junction stenosis, and vesicoureteral reflux

    SciTech Connect

    Devriendt, K.; Fryns, J.P.

    1995-11-20

    Robson et al. suggest that renal agenesis, multicystic renal dysplasia (MRD), and uretero-pelvic junction (PUJ) stenosis are pathogenetically related. They proposed a vascular disruption as the cause, with the variable severity of the disorder related to the timing of the abnormal blood supply to the ureteric bud. Alternatively, there exists convincing evidence of a genetic cause transmitted as an autosomal dominant disorder with variable expression, and with a candidate gene localized on chromosome arm 6p. Combinations of these urological malformations occur in the same individual or in different relatives in the same family. In several families with PUJ-stenosis, linkage with the HLA-locus on 6p has been demonstrated. Furthermore, we recently described a patient with a de novo reciprocal translocation involving the same region on 6p in a patient with bilateral multicystic renal dysplasia. Most disease-associated reciprocal translocations appear to have a breakpoint within a candidate gene: therefore, it is reasonable to hypothesize that the breakpoint on 6p in this patient resides within a gene causing MRD. This suggests that mutations in the same gene may lead either to PUJ-stenosis or, when the stenosis is complete, to MRD. A translocation is expected to result in a complete disruption of the gene, and this could explain the severe clinical expression of bilateral MRD. Less severe mutations in the same gene, associated with a partially conserved gene function, could lead to PUJ-stenosis. 11 refs.

  17. The macromelanophore locus and the melanoma oncogene Xmrk are separate genetic entities in the genome of Xiphophorus.

    PubMed Central

    Weis, S; Schartl, M

    1998-01-01

    Fish of the genus Xiphophorus are polymorphic for black pigmentation patterns. Certain intra- or interspecific hybrids exhibit enhanced expression of these patterns, leading in many cases to malignant melanoma. Because no recombination was ever observed between the pattern information and the genetic predisposition to develop melanoma after hybridization, a "tumor gene" (Tu) was postulated that encodes both phenotypes. A dominant oncogene, ONC-Xmrk, was then found to be necessary and sufficient for the transforming function of Tu. Here we present molecular evidence that ONC-Xmrk and the pigment pattern information are encoded by separate, although intimately linked loci. No ONC-Xmrk gene was present in the 15 Xiphophorus strains investigated which exhibit no black pigmentation pattern. Five different patterns from Xiphophorus maculatus, X. evelynae, X. milleri, X. cortezi, and X. montezumae were associated with ONC-Xmrk and were melanomagenic, while fish of X. helleri, X. variatus, X. nezahualcoyotl, and X. montezumae with five other patterns had no ONC-Xmrk and consequently did not produce hybrid melanoma. These data provide evidence that ONC-Xmrk is sufficient for tumorigenesis in Xiphophorus hybrids, and that a separate, pigment pattern-encoding locus is closely linked to it. PMID:9691046

  18. Genetic subtyping of Listeria monocytogenes via multiple-locus sequence typing using iap, sigB and actA

    PubMed Central

    YOSHIKAWA, Yuko; OCHIAI, Yoshitsugu; MOCHIZUKI, Mariko; FUJITA, Osamu; TAKANO, Takashi; HONDO, Ryo; UEDA, Fukiko

    2016-01-01

    Pulse field gel electrophoresis (PFGE) is widely used for listeriosis surveillance. Although this technique is effective for epidemiology, the data among laboratories are inconsistent. We previously reported a method for Listeria monocytogenes subtyping combined with sequence analysis of partial iap and whole genome restriction fragment length polymorphism (RFLP) using XbaI, ClaI (BanIII) and PstI. However, distinguishing subtypes was challenging, because the output comprised complicated fragment patterns. In this study, we aimed to establish a simple genotyping method that does not depend on visual observation, rather it focuses on multi-locus sequence typing (MLST) using three genes, iap, sigB and actA. Sixty-eight strains of L. monocytogenes including EGD-e as a reference strain were investigated to ensure consistency with previous data on the genetic characterization. All strains were grouped into 29 types by both analyses. Although there are some differences in classification, major clades included the same strains. Simpson’s indices of diversity (SID) by MLST and iap-RFLP-based typing were 0.967 (95% confidence interval [CI]: 0.955/0.978) and 0.967 (95% CI: 0.955/0.979), respectively. The discriminatory power of both methods can be considered almost identical. Compared with the results of 38 selected strains, the strains within the MLST clusters in this study coincided with those obtained using PFGE. Thus, the MLST strategy could help differentiate among L. monocytogenes isolates during epidemiological studies. PMID:27725353

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

    PubMed

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

    2005-11-01

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

  20. Genetic diversity and population genetic analysis of bovine MHC class II DRB3.2 locus in three Bos indicus cattle breeds of Southern India.

    PubMed

    Das, D N; Sri Hari, V G; Hatkar, D N; Rengarajan, K; Saravanan, R; Suryanarayana, V V S; Murthy, L K

    2012-12-01

    The present study was performed to evaluate the genetic polymorphism of BoLA-DRB3.2 locus in Malnad Gidda, Hallikar and Ongole South Indian Bos indicus cattle breeds, employing the PCR-RFLP technique. In Malnad Gidda population, 37 BoLA-DRB3.2 alleles were detected, including one novel allele DRB3*2503 (GenBank: HM031389) that was observed in the frequency of 1.87%. In Hallikar and Ongole populations, 29 and 21 BoLA-DRB3.2 alleles were identified, respectively. The frequencies of the most common BoLA-DRB3.2 alleles (with allele frequency > 5%), in Malnad Gidda population, were DRB3.2*15 (10.30%), DRB3*5702 (9.35%), DRB3.2*16 (8.41%), DRB3.2*23 (7.01%) and DRB3.2*09 (5.61%). In Hallikar population, the most common alleles were DRB3.2*11 (13.00%), DRB3.2*44 (11.60%), DRB3.2*31 (10.30%), DRB3.2*28 (5.48%) and DRB3.2*51 (5.48%). The most common alleles in Ongole population were DRB3.2*15 (22.50%), DRB3.2*06 (20.00%), DRB3.2*13 (13.30%), DRB3.2*12 (9.17%) and DRB3.2*23 (7.50%). A high degree of heterozygosity observed in Malnad Gidda (H(O) = 0.934, H(E) = 0.955), Hallikar (H(O) = 0.931, H(E) = 0.943) and Ongole (H(O) = 0.800, H(E) = 0.878) populations, along with F(IS) values close to F(IS) zero (Malnad Gidda: F(IS) = 0.0221, Hallikar: F(IS) = 0.0127 and Ongole: F(IS) = 0.0903), yielded nonsignificant P-values with respect to Hardy-Weinberg equilibrium probabilities revealing, no perceptible inbreeding, greater genetic diversity and characteristic population structure being preserved in the three studied cattle populations. The phylogenetic tree constructed based on the frequencies of BoLA-DRB3.2 alleles observed in 10 Bos indicus and Bos taurus cattle breeds revealed distinct clustering of specific Bos indicus cattle breeds, along with unique genetic differentiation observed among them. The results of this study demonstrated that the BoLA-DRB3.2 is a highly polymorphic locus, with significant breed-specific genetic diversities being present amongst the three studied

  1. Genetic diversity at the Dhn3 locus in Turkish Hordeum spontaneum populations with comparative structural analyses

    PubMed Central

    Uçarlı, Cüneyt; McGuffin, Liam J.; Çaputlu, Süleyman; Aravena, Andres; Gürel, Filiz

    2016-01-01

    We analysed Hordeum spontaneum accessions from 21 different locations to understand the genetic diversity of HsDhn3 alleles and effects of single base mutations on the intrinsically disordered structure of the resulting polypeptide (HsDHN3). HsDHN3 was found to be YSK2-type with a low-frequency 6-aa deletion in the beginning of Exon 1. There is relatively high diversity in the intron region of HsDhn3 compared to the two exon regions. We have found subtle differences in K segments led to changes in amino acids chemical properties. Predictions for protein interaction profiles suggest the presence of a protein-binding site in HsDHN3 that coincides with the K1 segment. Comparison of DHN3 to closely related cereals showed that all of them contain a nuclear localization signal sequence flanking to the K1 segment and a novel conserved region located between the S and K1 segments [E(D/T)DGMGGR]. We found that H. vulgare, H. spontaneum, and Triticum urartu DHN3s have a greater number of phosphorylation sites for protein kinase C than other cereal species, which may be related to stress adaptation. Our results show that the nature and extent of mutations in the conserved segments of K1 and K2 are likely to be key factors in protection of cells. PMID:26869072

  2. Effects of genetic and environmental factors on trait network predictions from quantitative trait locus data.

    PubMed

    Remington, David L

    2009-03-01

    The use of high-throughput genomic techniques to map gene expression quantitative trait loci has spurred the development of path analysis approaches for predicting functional networks linking genes and natural trait variation. The goal of this study was to test whether potentially confounding factors, including effects of common environment and genes not included in path models, affect predictions of cause-effect relationships among traits generated by QTL path analyses. Structural equation modeling (SEM) was used to test simple QTL-trait networks under different regulatory scenarios involving direct and indirect effects. SEM identified the correct models under simple scenarios, but when common-environment effects were simulated in conjunction with direct QTL effects on traits, they were poorly distinguished from indirect effects, leading to false support for indirect models. Application of SEM to loblolly pine QTL data provided support for biologically plausible a priori hypotheses of QTL mechanisms affecting height and diameter growth. However, some biologically implausible models were also well supported. The results emphasize the need to include any available functional information, including predictions for genetic and environmental correlations, to develop plausible models if biologically useful trait network predictions are to be made.

  3. Genetic studies of mrp, a locus essential for cellular aggregation and sporulation of Myxococcus xanthus.

    PubMed

    Sun, H; Shi, W

    2001-08-01

    Under starvation conditions, Myxococcus xanthus undergoes a complex developmental process which includes cellular aggregation and sporulation. A transposon insertion mutant (the Tn5-Omega280 mutant) with defects in both aggregation and sporulation was analyzed in this study. The Tn5-Omega280 mutant was found to have a disrupted NtrC-like response regulator designated Myxococcus regulatory protein B (mrpB). Further sequencing analyses revealed a histidine kinase homolog (mrpA) immediately upstream of mrpB and a cyclic AMP receptor protein-like transcriptional regulator (mrpC) downstream of mrpB. In-frame deletion analyses revealed that both the mrpB and mrpC genes were required for cellular aggregation and sporulation but that only mrpA was required for sporulation only. Site-specific mutagenesis of the putative phosphorylation site of MrpB, D58, showed that a D58A mutation caused defects in both aggregation and sporulation but that a D58E mutation resulted in only a sporulation defect. Further genetic and molecular analyses with reporter genes and reverse transcription-PCR indicated that mrpA and mrpB are cotranscribed but that mrpC is transcribed independently and that all of these genes are developmentally regulated. In addition, MrpB is essential for transcription of mrpC and MrpC regulates its own transcription. These data indicate that Mrp proteins are important components required for M. xanthus development. The complicated interaction between Mrp proteins may play an important role in regulating developmental gene expression in M. xanthus.

  4. Smooth and Rough Biotypes of Arcanobacterium haemolyticum Can Be Genetically Distinguished at the Arcanolysin Locus

    PubMed Central

    Ruther, Haley S.; Phillips, Kalyn; Ross, Dolores; Crawford, Alyssa; Weidner, M. Payton; Sammra, Osama; Lämmler, Christoph; McGee, David J.

    2015-01-01

    Arcanobacterium haemolyticum is a Gram-positive, β-hemolytic emerging human pathogen that is classified into smooth or rough biotypes. This bacterial species is also a rare pathogen of animals. Smooth biotypes possess smooth colony edges, are moderate to strong in β-hemolysis, and predominately cause wound infections. In contrast, rough biotypes possess rough and irregular colony edges, have weak to no β-hemolytic activity, and predominately cause pharyngitis. Using horse erythrocytes we confirmed that smooth isolates are generally more hemolytic than rough isolates. A hemolysin from A. haemolyticum, arcanolysin (aln/ALN), was recently discovered and is a member of the cholesterol-dependent cytolysin (CDC) family. PCR amplification of aln from all 36 smooth A. haemolyticum isolates yielded the expected 2.0 kb product. While 21 rough isolates yielded the 2.0 kb product, 16 isolates had a 3.2 kb product. The extra 1.2 kb segment was 99% identical to IS911 (insertion sequence) from Corynebacterium diphtheriae. PCR amplification and sequence analysis of the upstream region of aln revealed ~40 nucleotide polymorphisms among 73 clinical isolates from Finland, Denmark, Germany and United States (Nebraska). Remarkably, multi-sequence alignments of the aln upstream region demonstrated that ~90% of the isolates phylogenetically clustered as either smooths or roughs. Differential restriction enzyme analysis of the aln upstream region also demonstrated that the aln upstream region of most (~75%) smooth isolates was cleaved with ClaI while this region in most (~86%) rough isolates was cleaved with XcmI. We conclude that the aln upstream region can be used to genetically distinguish between smooth and rough biotypes of this important emerging pathogen. PMID:26382754

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

    PubMed

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

    2007-03-01

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

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

    PubMed Central

    Yu, Y.; Andrés, Jose A.

    2013-01-01

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

  7. A genetic locus and gene expression patterns associated with the priming effect on lettuce seed germination at elevated temperatures.

    PubMed

    Schwember, Andrés R; Bradford, Kent J

    2010-05-01

    Seeds of most cultivated varieties of lettuce (Lactuca sativa L.) fail to germinate at warm temperatures (i.e., above 25-30 degrees C). Seed priming (controlled hydration followed by drying) alleviates this thermoinhibition by increasing the maximum germination temperature. We conducted a quantitative trait locus (QTL) analysis of seed germination responses to priming using a recombinant inbred line (RIL) population derived from a cross between L. sativa cv. Salinas and L. serriola accession UC96US23. Priming significantly increased the maximum germination temperature of the RIL population, and a single major QTL was responsible for 47% of the phenotypic variation due to priming. This QTL collocated with Htg6.1, a major QTL from UC96US23 associated with high temperature germination capacity. Seeds of three near-isogenic lines (NILs) carrying an Htg6.1 introgression from UC96US23 in a Salinas genetic background exhibited synergistic increases in maximum germination temperature in response to priming. LsNCED4, a gene encoding a key enzyme (9-cis-epoxycarotinoid dioxygenase) in the abscisic acid biosynthetic pathway, maps precisely with Htg6.1. Expression of LsNCED4 after imbibition for 24 h at high temperature was greater in non-primed seeds of Salinas, of a second cultivar (Titan) and of NILs containing Htg6.1 compared to primed seeds of the same genotypes. In contrast, expression of genes encoding regulated enzymes in the gibberellin and ethylene biosynthetic pathways (LsGA3ox1 and LsACS1, respectively) was enhanced by priming and suppressed by imbibition at elevated temperatures. Developmental and temperature regulation of hormonal biosynthetic pathways is associated with seed priming effects on germination temperature sensitivity.

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

    PubMed

    Yu, Y; Andrés, Jose A

    2014-02-19

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

  9. Genetic Isolation, Cloning, and Analysis of a Mutator-Induced, Dominant Antimorph of the Maize amylose extender1 Locus.

    PubMed Central

    Stinard, PS; Robertson, DS; Schnable, PS

    1993-01-01

    We report the genetic identification, molecular cloning, and characterization of a dominant mutant at the amylose extender1 locus, Ae1-5180. The identities of our clones are corroborated by their ability to reveal DNA polymorphisms between seven wild-type revertants from Ae1-5180 relative to the Ae1-5180 mutant allele and between four of five independently derived, Mutator (Mu)-induced recessive ae1 alleles relative to their respective wild-type progenitor alleles. The Ae1-5180 mutation is associated with two Mu1 insertions flanked by complex rearrangements of ae1-related sequences. One of the Mu1 elements is flanked by inverted repeats of ae1-related DNA of at least 5.0 kb in length. This Mu1 element and at least some of this flanking inverted repeat DNA are absent or hypermethylated in six of seven wild-type revertants of Ae1-5180 that were analyzed. The second Mu1 element is flanked on one side by the 5.0-kb ae1-specific repeat and on the other side by a sequence that does not hybridize to the ae1-related repeat sequence. This second Mu1 element is present in revertants to the wild type and does not, therefore, appear to affect ae1 gene function. A 2.7-kb ae1 transcript can be detected in wild-type and homozygous ae1-Ref endosperms 20 days after pollination. This transcript is absent in endosperms containing one, two, or three doses of Ae1-5180. This result is consistent with a suppression model to explain the dominant gene action of Ae1-5180 and establishes Ae1-5180 as an antimorphic allele. Homozygous wild-type seedlings produce no detectable transcript, indicating some degree of tissue specificity for ae1 expression. Sequence analyses establish that ae1 encodes starch branching enzyme II. PMID:12271046

  10. Genetic variation at the MHC DRB1 locus is similar across Gunnison's prairie dog (Cynomys gunnisoni) colonies regardless of plague history.

    PubMed

    Cobble, Kacy R; Califf, Katy J; Stone, Nathan E; Shuey, Megan M; Birdsell, Dawn N; Colman, Rebecca E; Schupp, James M; Aziz, Maliha; Van Andel, Roger; Rocke, Tonie E; Wagner, David M; Busch, Joseph D

    2016-04-01

    Yersinia pestis was introduced to North America around 1900 and leads to nearly 100% mortality in prairie dog (Cynomys spp.) colonies during epizootic events, which suggests this pathogen may exert a strong selective force. We characterized genetic diversity at an MHC class II locus (DRB1) in Gunnison's prairie dog (C. gunnisoni) and quantified population genetic structure at the DRB1 versus 12 microsatellite loci in three large Arizona colonies. Two colonies, Seligman (SE) and Espee Ranch (ES), have experienced multiple plague-related die-offs in recent years, whereas plague has never been documented at Aubrey Valley (AV). We found fairly low allelic diversity at the DRB1 locus, with one allele (DRB1*01) at high frequency (0.67-0.87) in all colonies. Two other DRB1 alleles appear to be trans-species polymorphisms shared with the black-tailed prairie dog (C. ludovicianus), indicating that these alleles have been maintained across evolutionary time frames. Estimates of genetic differentiation were generally lower at the MHC locus (F ST = 0.033) than at microsatellite markers (F ST = 0.098). The reduced differentiation at DRB1 may indicate that selection has been important for shaping variation at MHC loci, regardless of the presence or absence of plague in recent decades. However, genetic drift has probably also influenced the DRB1 locus because its level of differentiation was not different from that of microsatellites in an F ST outlier analysis. We then compared specific MHC alleles to plague survivorship in 60 C. gunnisoni that had been experimentally infected with Y. pestis. We found that survival was greater in individuals that carried at least one copy of the most common allele (DRB1*01) compared to those that did not (60% vs. 20%). Although the sample sizes of these two groups were unbalanced, this result suggests the possibility that this MHC class II locus, or a nearby linked gene, could play a role in plague survival.

  11. Genetic variation at the MHC DRB1 locus is similar across Gunnison's prairie dog (Cynomys gunnisoni) colonies regardless of plague history

    USGS Publications Warehouse

    Cobble, Kacy R.; Califf, Katy J.; Stone, Nathan E.; Shuey, Megan M.; Birdsell, Dawn; Colman, Rebecca E.; Schupp, James M.; Aziz, Maliha; Van Andel, Roger; Rocke, Tonie E.; Wagner, David M.; Busch, Joseph D.

    2016-01-01

    Yersinia pestis was introduced to North America around 1900 and leads to nearly 100% mortality in prairie dog (Cynomys spp.) colonies during epizootic events, which suggests this pathogen may exert a strong selective force. We characterized genetic diversity at an MHC class II locus (DRB1) in Gunnison's prairie dog (C. gunnisoni) and quantified population genetic structure at the DRB1versus 12 microsatellite loci in three large Arizona colonies. Two colonies, Seligman (SE) and Espee Ranch (ES), have experienced multiple plague-related die-offs in recent years, whereas plague has never been documented at Aubrey Valley (AV). We found fairly low allelic diversity at the DRB1 locus, with one allele (DRB1*01) at high frequency (0.67–0.87) in all colonies. Two otherDRB1 alleles appear to be trans-species polymorphisms shared with the black-tailed prairie dog (C. ludovicianus), indicating that these alleles have been maintained across evolutionary time frames. Estimates of genetic differentiation were generally lower at the MHC locus (FST = 0.033) than at microsatellite markers (FST = 0.098). The reduced differentiation at DRB1 may indicate that selection has been important for shaping variation at MHC loci, regardless of the presence or absence of plague in recent decades. However, genetic drift has probably also influenced theDRB1 locus because its level of differentiation was not different from that of microsatellites in anFST outlier analysis. We then compared specific MHC alleles to plague survivorship in 60C. gunnisoni that had been experimentally infected with Y. pestis. We found that survival was greater in individuals that carried at least one copy of the most common allele (DRB1*01) compared to those that did not (60% vs. 20%). Although the sample sizes of these two groups were unbalanced, this result suggests the possibility that this MHC class II locus, or a nearby linked gene, could play a role in plague survival.

  12. Association Genetics of Populus trichocarpa or Resequencing in Populus: Towards Genome Wide Association Genetics (2011 JGI User Meeting)

    SciTech Connect

    Tuskan, Gerry

    2011-03-23

    The U.S. Department of Energy Joint Genome Institute (JGI) invited scientists interested in the application of genomics to bioenergy and environmental issues, as well as all current and prospective users and collaborators, to attend the annual DOE JGI Genomics of Energy & Environment Meeting held March 22-24, 2011 in Walnut Creek, Calif. The emphasis of this meeting was on the genomics of renewable energy strategies, carbon cycling, environmental gene discovery, and engineering of fuel-producing organisms. The meeting features presentations by leading scientists advancing these topics. Gerry Tuskan of Oak Ridge National Laboratory on "Resequencing in Populus: Towards Genome Wide Association Genetics" at the 6th annual Genomics of Energy & Environment Meeting on March 23, 2011

  13. Association Genetics of Populus trichocarpa or Resequencing in Populus: Towards Genome Wide Association Genetics (2011 JGI User Meeting)

    ScienceCinema

    Tuskan, Gerry

    2016-07-12

    The U.S. Department of Energy Joint Genome Institute (JGI) invited scientists interested in the application of genomics to bioenergy and environmental issues, as well as all current and prospective users and collaborators, to attend the annual DOE JGI Genomics of Energy & Environment Meeting held March 22-24, 2011 in Walnut Creek, Calif. The emphasis of this meeting was on the genomics of renewable energy strategies, carbon cycling, environmental gene discovery, and engineering of fuel-producing organisms. The meeting features presentations by leading scientists advancing these topics. Gerry Tuskan of Oak Ridge National Laboratory on "Resequencing in Populus: Towards Genome Wide Association Genetics" at the 6th annual Genomics of Energy & Environment Meeting on March 23, 2011

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

    PubMed

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

    1994-07-01

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

  15. Genetic modification stimulated by the induction of a site-specific break distant from the locus of correction in haploid and diploid yeast Saccharomyces cerevisiae.

    PubMed

    Stuckey, Samantha; Storici, Francesca

    2014-01-01

    Generation of a site-specific break at a genomic locus to stimulate homologous recombination (HR) is used in many organisms to efficiently target genes for various types of genetic modification. Additionally, a site-specific chromosomal break can be used to trigger HR at genomic regions distant from the break, thereby largely expanding the region available for introducing desired mutations. In contrast to the former approach, the latter presents an alternative way in which genes can be efficiently modified also when it is not possible or desirable to introduce a break in the vicinity of the targeting locus. This type of in vivo site-directed mutagenesis distant from a break can be accomplished in the yeast model organism Saccharomyces cerevisiae because the generation of a double-strand break (DSB) in yeast chromosomal DNA activates HR at long regions upstream and downstream from the break site. Here we provide a protocol for efficiently altering a yeast chromosomal locus following the induction of a DSB several kilobase pairs distant from the site of gene correction. The techniques described can be used in both diploid and haploid yeast strains, and we provide examples of the gene correction assays.

  16. CATCH 22 syndrome: report of 7 infants with follow-up data and review of the recent advancements in the genetic knowledge of the locus 22q11.

    PubMed

    Sergi, C; Serpi, M; Müller-Navia, J; Schnabel, P A; Hagl, S; Otto, H F; Ulmer, H E

    1999-06-01

    CATCH 22 is a medical acronym for Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcemia, and a variable deletion on chromosome 22. The deletion within the chromosome region of 22q11 may occur in patients with three well-described dysmorphologic+ cardiological syndromes: DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), and conotruncal anomaly face syndrome (CTAFS). We report in detail seven infants with a deletion of the locus 22q11 showing overlapping clinical features of DGS and CTAFS with complex congenital heart defects (double outlet right ventricle, atresia or stenosis of the pulmonary valve, atrial and ventricular septal defects, patent ductus arteriosus, tetralogy of Fallot, major aortopulmonary collateral arteries, arcus aortae dexter, and persistence of the left superior vena cava). A homograft was implanted between the right ventricle and the main stem of the pulmonary artery in 2 patients, while a balloon valvuloplastic of the pulmonary valve was performed in one patient only. Pulmonary hemorrhage, acute hypoxia, and Aspergillus pneumonia were the complications. Death occurred in three out of seven patients. Recent advancements in the genetic knowledge of the locus 22q11 are described. Since the locus 22q11 is highly heterogeneous, the CATCH 22 acronym should be used and temporarily the old eponyms should be abandoned waiting for the identification of the different genes.

  17. 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.

  18. Genetic variation at the PCSK9 locus, low density lipoproteins, response to pravastatin and coronary heart disease: results from PROSPER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucle...

  19. Locus BoLA-DRB3 is just an ordinary site of the polygene when explaining genetic variance of somatic cell count and milk yield.

    PubMed

    Oprzadek, Jolanta; Sender, Grazyna; Pawlik, Adrianna; Lukaszewicz, Marek

    2015-11-01

    The study aimed at clarifying the problem of the hitherto contradictory results regarding usefulness of BoLA-DRB3 locus as a marker in selection against mastitis and for milk yield. Treating the BoLA-DRB3 locus effect as random was proposed in place of considering it fixed. Somatic cell counts and milk yields recorded monthly on a test day (22,424) of 619 Polish Holstein cows genotyped for BoLA-DRB3 were analysed with an animal model including a random effect for genotype at this locus. The BoLA-DRB3 alleles were defined as restriction patterns obtained with three endonucleases. Two alternative BoLA-DRB3 additive genotype (co)variance structures were constructed for 161 genotypes recorded. One was based on the allelic similarity of the genotypes resulting in element values of 0 (no common allele), 0.5 (one allele in common), and 1 (diagonal). The other considered restriction site similarity (up to 3 in 1 allele) giving element values of 0 (no common restriction sites) and then increasingly in steps of 1/6 up to 6/6 (diagonal), where the numerator represents the number of common sites between genotypes. The DRB3 variance component for the natural logarithm of somatic cell count did not exceed 0.006 of the polygenic additive component or 0.003 for milk yield. Hence, unless we fail to detect the causative site or to properly define traits being the projection of a site, the effect of the genotype at the BoLA-DRB3 locus does not explain variation in somatic cell count and milk yield at a degree expected of a genetic marker.

  20. 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

  1. Genetic analysis of the genes involved in synthesis of the lipopolysaccharide core in Escherichia coli K-12: three operons in the rfa locus.

    PubMed Central

    Roncero, C; Casadaban, M J

    1992-01-01

    The region of the Escherichia coli K-12 chromosome encoding the enzymes responsible for the synthesis of responsible for the synthesis of the lipopolysaccharide (LPS) core has been cloned in vivo by using a mini-Mu vector. This region, formerly known as the rfa locus, comprises 18 kb of DNA between the markers tdh and rpmBG. Results of in vitro mutagenesis of this region with MudII1734 indicate the presence of at least 17 open reading frames or genes, a number considerably higher than expected on the basis of genetic and biochemical studies. Specific insertions in different genes have been recombined into the chromosome, and the mutations have been phenotypically characterized. Complementation analysis indicates that these genes are arranged in three different operons transcribed in opposite directions. A detailed physical map of this region has been constructed on the basis of complementation analysis, fusion protein data, and phenotypic characterizations. Additionally, the role of some genes in the synthesis of LPS has been defined by complementation analysis with known Salmonella typhimurium LPS mutants. The genetic organization of this locus seems to be identical in E. coli K-12 and S. typhimurium. Images PMID:1577693

  2. Identification of Genetic Loci Affecting the Severity of Symptoms of Hirschsprung Disease in Rats Carrying Ednrbsl Mutations by Quantitative Trait Locus Analysis

    PubMed Central

    Torigoe, Daisuke; Lei, Chuzhao; Lan, Xianyong; Chen, Hong; Sasaki, Nobuya; Wang, Jinxi; Agui, Takashi

    2015-01-01

    Hirschsprung’s disease (HSCR) is a congenital disease in neonates characterized by the absence of the enteric ganglia in a variable length of the distal colon. This disease results from multiple genetic interactions that modulate the ability of enteric neural crest cells to populate developing gut. We previously reported that three rat strains with different backgrounds (susceptible AGH-Ednrbsl/sl, resistant F344-Ednrbsl/sl, and LEH-Ednrbsl/sl) but the same null mutation of Ednrb show varying severity degrees of aganglionosis. This finding suggests that strain-specific genetic factors affect the severity of HSCR. Consistent with this finding, a quantitative trait locus (QTL) for the severity of HSCR on chromosome (Chr) 2 was identified using an F2 intercross between AGH and F344 strains. In the present study, we performed QTL analysis using an F2 intercross between the susceptible AGH and resistant LEH strains to identify the modifier/resistant loci for HSCR in Ednrb-deficient rats. A significant locus affecting the severity of HSCR was also detected within the Chr 2 region. These findings strongly suggest that a modifier gene of aganglionosis exists on Chr 2. In addition, two potentially causative SNPs (or mutations) were detected upstream of a known HSCR susceptibility gene, Gdnf. These SNPs were possibly responsible for the varied length of gut affected by aganglionosis. PMID:25790447

  3. 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.

  4. Movable Genetic Elements: Detection of Changes in Maize DNA at the Shrunken Locus Due to the Intervention of Ds Elements

    DOE R&D Accomplishments Database

    Burr, B.; Burr, F.A.

    1980-05-28

    This report describes our initial attempts at the molecular characterization of a maize controlling element. We have prepared a cDNA probe and used it to detect changes at a locus where Ds elements are found. Evidence of their presence are indicated by changes in the restriction patterns, but there is as yet no information on the physical nature of the controlling elements nor on the kinds of rearrangements they cause.

  5. Movable genetic elements: detection of changes in maize DNA at the Shrunken locus due to the intervention of Ds elements

    SciTech Connect

    Burr, B.; Burr, F.A.

    1980-05-28

    This report describes our initial attempts at the molecular characterization of a maize controlling element. We have prepared a cDNA probe and used it to detect changes at a locus where Ds elements are found. Evidence of their presence are indicated by changes in the restriction patterns, but there is as yet no information on the physical nature of the controlling elements nor on the kinds of rearrangements they cause.

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

    PubMed

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

    2001-09-01

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

  7. LMNA cardiomyopathy: cell biology and genetics meet clinical medicine.

    PubMed

    Lu, Jonathan T; Muchir, Antoine; Nagy, Peter L; Worman, Howard J

    2011-09-01

    Mutations in the LMNA gene, which encodes A-type nuclear lamins (intermediate filament proteins expressed in most differentiated somatic cells), cause a diverse range of diseases, called laminopathies, that selectively affect different tissues and organ systems. The most prevalent laminopathy is cardiomyopathy with or without different types of skeletal muscular dystrophy. LMNA cardiomyopathy has an aggressive clinical course with higher rates of deadly arrhythmias and heart failure than most other heart diseases. As awareness among physicians increases, and advances in DNA sequencing methods make the genetic diagnosis of LMNA cardiomyopathy more common, cardiologists are being faced with difficult questions regarding patient management. These questions concern the optimal use of intracardiac cardioverter defibrillators to prevent sudden death from arrhythmias, and medical interventions to prevent heart damage and ameliorate heart failure symptoms. Data from a mouse model of LMNA cardiomyopathy suggest that inhibitors of mitogen-activated protein kinase (MAPK) signaling pathways are beneficial in preventing and treating cardiac dysfunction; this basic research discovery needs to be translated to human patients.

  8. A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers

    PubMed Central

    Benton, Miles C.; Lea, Rodney A.; Macartney-Coxson, Donia; Hanna, Michelle; Eccles, David A.; Carless, Melanie A.; Chambers, Geoffrey K.; Bellis, Claire; Goring, Harald H.; Curran, Joanne E.; Harper, Jacquie L.; Gibson, Gregory; Blangero, John; Griffiths, Lyn R.

    2015-01-01

    Multiphenotype genome-wide association studies (GWAS) may reveal pleiotropic genes, which would remain undetected using single phenotype analyses. Analysis of large pedigrees offers the added advantage of more accurately assessing trait heritability, which can help prioritise genetically influenced phenotypes for GWAS analysis. In this study we performed a principal component analysis (PCA), heritability (h2) estimation and pedigree-based GWAS of 37 cardiovascular disease -related phenotypes in 330 related individuals forming a large pedigree from the Norfolk Island genetic isolate. PCA revealed 13 components explaining >75% of the total variance. Nine components yielded statistically significant h2 values ranging from 0.22 to 0.54 (P<0.05). The most heritable component was loaded with 7 phenotypic measures reflecting metabolic and renal dysfunction. A GWAS of this composite phenotype revealed statistically significant associations for 3 adjacent SNPs on chromosome 1p22.2 (P<1x10-8). These SNPs form a 42kb haplotype block and explain 11% of the genetic variance for this renal function phenotype. Replication analysis of the tagging SNP (rs1396315) in an independent US cohort supports the association (P = 0.000011). Blood transcript analysis showed 35 genes were associated with rs1396315 (P<0.05). Gene set enrichment analysis of these genes revealed the most enriched pathway was purine metabolism (P = 0.0015). Overall, our findings provide convincing evidence for a major pleiotropic effect locus on chromosome 1p22.2 influencing risk of renal dysfunction via purine metabolism pathways in the Norfolk Island population. Further studies are now warranted to interrogate the functional relevance of this locus in terms of renal pathology and cardiovascular disease risk. PMID:26474483

  9. 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.

  10. Characterization of genetic polymorphism of the bovine lymphocyte antigen DRB3.2 locus in Kankrej cattle (Bos indicus).

    PubMed

    Behl, J D; Verma, N K; Behl, R; Mukesh, M; Ahlawat, S P S

    2007-06-01

    Bovine lymphocyte antigen DRB 3.2 (BoLA-DRB3.2) gene encodes for the beta chain of the major histocompatibility complex (MHC) class II molecule in cattle, which is a glycoprotein present on the surface of antigen-presenting cells. This locus shows extensive polymorphism in it. The objective of the present study was to genotype the BoLA-DRB3.2 locus in Kankrej cattle (n = 50) by PCR-RFLP. Bovine DNA was isolated from aliquots of whole blood. Primers specific for exon 2 of the bovine lymphocyte antigen (BoLA)-DRB3 gene were used to amplify the region. The 304-bp amplified product of the DRB3 gene was separately digested with restriction endonucleases RsaI, BstYI, and Hae III. Twenty-four BoLA-DRB 3.2 alleles were identified with frequencies ranging from 1 to 22.0%. Twenty-one alleles of the total 24 alleles were similar to those reported earlier; 3 alleles were new and had not been reported previously. The allele BoLA-DRB3.2*34 occurred at the highest frequency of 22% (approx.) in the Kankrej animals studied. Six alleles (BoLA-DRB3.2 *34, *15, *06, *20, *37, and *20) accounted for almost 71% of the total alleles observed to be present in the Kankrej animals. All the new alleles observed were present at frequencies of 1%. The results obtained in the present study demonstrated that the BoLA DRB3.2 locus is highly polymorphic in the Kankrej cattle.

  11. [Genetic variation at the pantophysin (PanI) locus in North-East Arctic cod Gadus morhua L. (Gadiformes: Gadidae) population in the Barents Sea and adjacent waters].

    PubMed

    Makeenko, G A; Volkov, A A; Mugue, N S; Zelenina, D A

    2014-12-01

    We investigated polymorphisms in the pantophysin gene (Pan I locus) in a population of North-East Arctic cod, Gadus morhua L., throughout its foraging area in the Barents Sea and adjacent waters. Correlations between the frequencies of Pan I alleles and habitat conditions, such as depth and temperature, were explored. This study was based on a large number of specimens (2210 individuals) of different age and wide geographic sampling coverage. The frequency of the Pan I(A) allele, a known genetic marker of coastal cod, varied from zero to 0.47. Allele frequencies correlated with depth at the sampling location but not with bottom water temperatures. We observed variations in Pan I(A) frequencies among different age cohorts from the same area. The most prominent shift in Pan I polymorphism was detected at the early stages of the fish life cycle, between pelagic juveniles and benthic cod. We found that the Pan I(A) allele frequency in pelagic yearling cod was essentially same throughout the studied areas in the Barents Sea. In turn, juveniles settling at the northern and deep water locations showed a significant decrease in the allele frequency. In contrast, the frequency of the Pan I(A) allele remained constant in juveniles settling in shallow waters when compared to the pelagic stage. These results confirm the selective nature of the cod Pan I locus and indicate that selection process acting on individuals with different genotypes at the Pan I locus leads to the formation of a stable spatial distribution of allele frequencies observed in adult cod.

  12. Intra-and inter-population genetic diversity at the HLA-DQA1 locus and their implications for parentage analysis and human identification

    SciTech Connect

    Rivas, F. |; Cerda-Flores, R. |; Zhong, Y.

    1994-09-01

    HLA-DQA1 locus, studied by PCR-based sequence specific oligonucleotide probes, is highly polymorphic in all populations thus far studied. From the literature we compiled genotype and allele frequency data at this locus for 87 populations to examine the pattern of intra- and inter- population genetic diversity. In general, allele frequency variations in populations are consistent with their ethno-history, although small isolated populations (e.g. Pacific Islanders) exhibit somewhat disparate variations of allele frequencies. A nested gene diversity analysis of 41 populations, classified into 5 ethnic groups (African, n = 3; Caucasian, n = 18; American Native, n = 3; Asian, n = 8; Pacific Islanders, n = 9) showed that the total gene diversity (80.4%) is largely (95%) due to intra-population variation. Only 3% of the gene diversity is due to inter-population within ethnic group variation, with the remaining 2% due to between ethnic group variation. In terms of average heterozygosity, probability of paternity exlusion, and probability of individual identification, the inter-ethnic group variation is larger than that between poulation samples within the ethnic groups. No significant departure from Hardy-Weinberg expectations of genotype frequencies was observed in any population. With an average heterozygosity of 77% around the world, this locus provides a 57% chance of exclusion of a falsely accused person from paternity, and is able to exclude 91% of individuals for identification purposes. In terms of allele fequencies, the geometric positions of the admixed populations (e.g. African-Americans and American-Hispanics) are consistent with their admixture estimates in their gene pool.

  13. 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.

  14. 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

  15. 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.

  16. Genetic Interactions at the Fla10 Locus: Suppressors and Synthetic Phenotypes That Affect the Cell Cycle and Flagellar Function in Chlamydomonas Reinhardtii

    PubMed Central

    Lux-III, F. G.; Dutcher, S. K.

    1991-01-01

    Through the isolation of suppressors of temperature-sensitive flagellar assembly mutations at the FLA10 locus of Chlamydomonas reinhardtii, we have identified six other genes involved in flagellar assembly. Mutations at these suppressor loci, termed SUF1-SUF6, display allele specificity with respect to which fla10(-) mutant alleles they suppress. An additional mutation, apm1-122, which confers resistance to the plant herbicides amiprophos-methyl and oryzalin, was also found to interact with mutations at the FLA10 locus. The apm1-122 mutation in combination with three fla10(-) mutant alleles results in synthetic cold-sensitive cell division defects, and in combination with an additional pseudo-wild-type fla10(-) allele yields a synthetic temperature-sensitive flagellar motility phenotype. Based upon the genetic interactions of these loci, we propose that the FLA10 gene product interacts with multiple components of the flagellar apparatus and plays a role both in flagellar assembly and in the cell cycle. PMID:1874415

  17. 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.

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

    SciTech Connect

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

    1994-09-01

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

  19. 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...

  20. Plasmodium falciparum genetic diversity can be characterised using the polymorphic merozoite surface antigen 2 (MSA-2) gene as a single locus marker.

    PubMed

    Prescott, N; Stowers, A W; Cheng, Q; Bobogare, A; Rzepczyk, C M; Saul, A

    1994-02-01

    The genetic diversity of Solomon Island Plasmodium falciparum isolates was examined using MSA-2 as a single locus marker. Amplification of MSA-2 gene fragments showed size polymorphism and the presence of mixed infections. Sequence analysis indicated a global representation of MSA-2 alleles with representatives of 3D7/CAMP allelic subfamilies and the FCQ-27 allelic family being identified. A simplified method of characterisation, utilising PCR-RFLPs of MSA-2 gene fragments, was developed. The RFLPs allowed identification of allelic families and further distinction within the 3D7/CAMP family. The amplification of MSA-2 gene fragments from culture derived lines revealed a loss of diversity for a number of Solomon Island isolates. Genomic diversity was confirmed for Solomon Island lines, along with Papua New Guinean and Thai lines, by the generation of 7H8/6 fingerprints. All lines were distinct and band sharing frequencies and Wagner tree construction failed to identify any geographic clustering.

  1. Genetic Analysis of Natural Variation in Antirrhinum Scent Profiles Identifies BENZOIC ACID CARBOXYMETHYL TRANSFERASE As the Major Locus Controlling Methyl Benzoate Synthesis

    PubMed Central

    Ruiz-Hernández, Victoria; Hermans, Benjamin; Weiss, Julia; Egea-Cortines, Marcos

    2017-01-01

    The Antirrhinum genus has a considerable complexity in the scent profiles produced by different species. We have analyzed the genetic differences between A. majus and A. linkianum, two species divergent in the emission of methyl benzoate, methyl cinnamate, acetophenone, and ocimene. The genetic analysis showed that all compounds segregated in a Mendelian fashion attributable to one or two loci with simple or epistatic interactions. Several lines lacked methyl benzoate, a major Volatile Organic Compound emitted by A. majus but missing in A. linkianum. Using a candidate gene approach, we found that the BENZOIC ACID CARBOXYMETHYL TRANSFERASE from A. linkianum appeared to be a null allele as we could not detect mRNA expression. The coding region did not show significant differences that could explain the loss of expression. The intron-exon boundaries was also conserved indicating that there is no alternative splicing in A. linkianum as compared to A. majus. However, it showed multiple polymorphisms in the 5′ promoter region including two insertions, one harboring an IDLE MITE transposon with additional sequences with high homology to the PLENA locus and a second one with somewhat lower homology to the regulatory region of the VENOSA locus. It also had a 778 bp deletion as compared to the A. majus BAMT promoter region. Our results show that the differences in scent emission between A. majus and A. linkianum may be traced back to single genes involved in discrete biosynthetic reactions such as benzoic acid methylation. Thus, natural variation of this complex trait maybe the result of combinations of wild type, and loss of function alleles in different genes involved in discrete VOCs biosynthesis. Furthermore, the presence of active transposable elements in the genus may account for rapid evolution and instability, raising the possibility of adaptation to local pollinators. PMID:28154577

  2. Genetic Analysis of Natural Variation in Antirrhinum Scent Profiles Identifies BENZOIC ACID CARBOXYMETHYL TRANSFERASE As the Major Locus Controlling Methyl Benzoate Synthesis.

    PubMed

    Ruiz-Hernández, Victoria; Hermans, Benjamin; Weiss, Julia; Egea-Cortines, Marcos

    2017-01-01

    The Antirrhinum genus has a considerable complexity in the scent profiles produced by different species. We have analyzed the genetic differences between A. majus and A. linkianum, two species divergent in the emission of methyl benzoate, methyl cinnamate, acetophenone, and ocimene. The genetic analysis showed that all compounds segregated in a Mendelian fashion attributable to one or two loci with simple or epistatic interactions. Several lines lacked methyl benzoate, a major Volatile Organic Compound emitted by A. majus but missing in A. linkianum. Using a candidate gene approach, we found that the BENZOIC ACID CARBOXYMETHYL TRANSFERASE from A. linkianum appeared to be a null allele as we could not detect mRNA expression. The coding region did not show significant differences that could explain the loss of expression. The intron-exon boundaries was also conserved indicating that there is no alternative splicing in A. linkianum as compared to A. majus. However, it showed multiple polymorphisms in the 5' promoter region including two insertions, one harboring an IDLE MITE transposon with additional sequences with high homology to the PLENA locus and a second one with somewhat lower homology to the regulatory region of the VENOSA locus. It also had a 778 bp deletion as compared to the A. majus BAMT promoter region. Our results show that the differences in scent emission between A. majus and A. linkianum may be traced back to single genes involved in discrete biosynthetic reactions such as benzoic acid methylation. Thus, natural variation of this complex trait maybe the result of combinations of wild type, and loss of function alleles in different genes involved in discrete VOCs biosynthesis. Furthermore, the presence of active transposable elements in the genus may account for rapid evolution and instability, raising the possibility of adaptation to local pollinators.

  3. Genetic studies of the Fv-1 locus of mice: linkage with Gpd-1 in recombinant inbred lines.

    PubMed Central

    Taylor, B A; Bedigian, H G; Meier, H

    1977-01-01

    Multiple recombinant inbred lines, derived from crosses between strains permissive to N-tropic murine leukemia viruses (Fv-1n) and strains permissive to B-tropic murine leukemia viruses (Fv-1b), have been characterized as to Fv-1 genotype and other chromosome 4 markers, including the closely linked hexose-6-phosphate dehydrogenase isozyme locus (Gpd-1). Only one recombinant between Fv-1 and Gpd-1 was found among 45 lines tested. On this basis, the distance between Fv-1 and Gpd-1 is estimated to be 0.6 centimorgans. None of the lines was either resistant or susceptible to both N- and B-tropic viruses. Nineteen other inbred strains, previously untested, were characterized as either Fv-1n or Fv-1b. PMID:196096

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

    SciTech Connect

    Russell, L.B.

    1982-01-01

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

  5. An omnibus permutation test on ensembles of two-locus analyses can detect pure epistasis and genetic heterogeneity in genome-wide association studies.

    PubMed

    Setsirichok, Damrongrit; Tienboon, Phuwadej; Jaroonruang, Nattapong; Kittichaijaroen, Somkit; Wongseree, Waranyu; Piroonratana, Theera; Usavanarong, Touchpong; Limwongse, Chanin; Aporntewan, Chatchawit; Phadoongsidhi, Marong; Chaiyaratana, Nachol

    2013-01-01

    This article presents the ability of an omnibus permutation test on ensembles of two-locus analyses (2LOmb) to detect pure epistasis in the presence of genetic heterogeneity. The performance of 2LOmb is evaluated in various simulation scenarios covering two independent causes of complex disease where each cause is governed by a purely epistatic interaction. Different scenarios are set up by varying the number of available single nucleotide polymorphisms (SNPs) in data, number of causative SNPs and ratio of case samples from two affected groups. The simulation results indicate that 2LOmb outperforms multifactor dimensionality reduction (MDR) and random forest (RF) techniques in terms of a low number of output SNPs and a high number of correctly-identified causative SNPs. Moreover, 2LOmb is capable of identifying the number of independent interactions in tractable computational time and can be used in genome-wide association studies. 2LOmb is subsequently applied to a type 1 diabetes mellitus (T1D) data set, which is collected from a UK population by the Wellcome Trust Case Control Consortium (WTCCC). After screening for SNPs that locate within or near genes and exhibit no marginal single-locus effects, the T1D data set is reduced to 95,991 SNPs from 12,146 genes. The 2LOmb search in the reduced T1D data set reveals that 12 SNPs, which can be divided into two independent sets, are associated with the disease. The first SNP set consists of three SNPs from MUC21 (mucin 21, cell surface associated), three SNPs from MUC22 (mucin 22), two SNPs from PSORS1C1 (psoriasis susceptibility 1 candidate 1) and one SNP from TCF19 (transcription factor 19). A four-locus interaction between these four genes is also detected. The second SNP set consists of three SNPs from ATAD1 (ATPase family, AAA domain containing 1). Overall, the findings indicate the detection of pure epistasis in the presence of genetic heterogeneity and provide an alternative explanation for the aetiology of T1D

  6. Next-Generation Genetics in Plants: Evolutionary Trade-off, Immunity and Speciation (2010 JGI User Meeting)

    SciTech Connect

    Wiegel, Detlef

    2010-03-25

    Detlef Wiegel from the Max Planck Institute for Developmental Biology on "Next-generation genetics in plants: Evolutionary tradeoffs, immunity and speciation" on March 25, 2010 at the 5th Annual DOE JGI User Meeting

  7. Next-Generation Genetics in Plants: Evolutionary Trade-off, Immunity and Speciation (2010 JGI User Meeting)

    ScienceCinema

    Wiegel, Detlef

    2016-07-12

    Detlef Wiegel from the Max Planck Institute for Developmental Biology on "Next-generation genetics in plants: Evolutionary tradeoffs, immunity and speciation" on March 25, 2010 at the 5th Annual DOE JGI User Meeting

  8. Genetic analysis of lipopolysaccharide core biosynthesis by Escherichia coli K-12: insertion mutagenesis of the rfa locus.

    PubMed Central

    Austin, E A; Graves, J F; Hite, L A; Parker, C T; Schnaitman, C A

    1990-01-01

    Tn10 insertions were selected on the basis of resistance to the lipopolysaccharide (LPS)-specific bacteriophage U3. The majority of these were located in a 2-kilobase region within the rfa locus, a gene cluster of about 18 kb that contains genes for LPS core biosynthesis. The rfa::Tn10 insertions all exhibited a deep rough phenotype that included hypersensitivity to hydrophobic antibiotics, a reduction in major outer membrane proteins, and production of truncated LPS. These mutations were complemented by a Clarke-Carbon plasmid known to complement rfa mutations of Salmonella typhimurium, and analysis of the insert from this plasmid showed that it contained genes for at least six polypeptides which appear to be arranged in the form of a complex operon. Defects in two of these genes were specifically implicated as the cause of the deep rough phenotype. One of these appeared to be rfaG, which encodes a function required for attachment of the first glucose residue to the heptose region of the core. The other gene did not appear to be directly involved in determination of the sugar composition of the core. We speculate that the product of this gene is involved in the attachment of phosphate or phosphorylethanolamine to the core and that it is the lack of one of these substituents which results in the deep rough phenotype. Images PMID:2168379

  9. [Analysis of genetic variations at M857 locus of the a1-Fucosy- trans-ferase (FUT1) ORF in pigs].

    PubMed

    Wu, Sheng-Long; Bao, Wen-Bin; Ju, Hui-Ping; Zhu, Guo-Qiang; Li, Bi-Chun; Chen, Guo-Hong

    2007-09-01

    Enterotoxigenic Escherichia coli F18 (ETEC F18) is the main pathogen that causes edema disease and post-weaning diarrhea in piglets, and a1-fucosytransferase (FUT1) gene has been identified as a receptor gene encoding the receptor for ETEC F18 bacteria. In this study, the method of PCR-RFLP was used to investigate the among 21 breeds including one wild boar breed and 20 western commercial and Chinese native pig breeds (populations). The results showed that none of the individuals in all 21 breeds possessed the resistant AA genotype, the genetic polymorphisms of the FUT1 locus were only detected in two western pig breeds (Duroc and Yorkshire), Lingao pig and hybrid pig breeds, while the wild boar and all the other Chinese pig breeds only possessed the susceptible GG genotype. The results indicated that Chinese native pig breeds, unlike western pig breeds, lack the genetic background on the resistance to ETEC F18 bacteria. This may be owe to their different origination, as the resistance gene to ETEC F18 might be originated from European wild boar. It was also inferred that edema disease and post-weaning diarrhea caused by ETEC F18 had close relationship with the growth speed of pigs.

  10. Characterization of the genetic locus responsible for the production of ABP-118, a novel bacteriocin produced by the probiotic bacterium Lactobacillus salivarius subsp. salivarius UCC118.

    PubMed

    Flynn, Sarah; van Sinderen, Douwe; Thornton, Gerardine M; Holo, Helge; Nes, Ingolf F; Collins, J Kevin

    2002-04-01

    ABP-118, a small heat-stable bacteriocin produced by Lactobacillus salivarius subsp. salivarius UCC118, a strain isolated from the ileal-caecal region of the human gastrointestinal tract, was purified to homogeneity. Using reverse genetics, a DNA fragment specifying part of ABP-118 was identified on a 10769 bp chromosomal region. Analysis of this region revealed that ABP-118 was a Class IIb two-peptide bacteriocin composed of Abp118alpha, which exhibited the antimicrobial activity, and Abp118beta, which enhanced the antimicrobial activity. The gene conferring strain UCC118 immunity to the action of ABP-118, abpIM, was identified downstream of the abp118beta gene. Located further downstream of abp118beta, several ORFs were identified whose deduced proteins resembled those of proteins involved in bacteriocin regulation and secretion. Heterologous expression of ABP-118 was achieved in Lactobacillus plantarum, Lactococcus lactis and Bacillus cereus. In addition, the abp118 locus encoded an inducing peptide, AbpIP, which was shown to play a role in the regulation of ABP-118 production. This novel bacteriocin is, to the authors' knowledge, the first to be isolated from a known human probiotic bacterium and to be characterized at the genetic level.

  11. DEVELOPMENT OF EPIC GENETIC MARKERS AND THE UTILITY OF A MULTI-LOCUS, MULTI-TAXA PHYLOGEOGRAPHICAL APPROACH TO EXAMINING PATTERNS OF GENETIC DIVERSITY

    EPA Science Inventory

    Use of population genetic measures for assessing the structure of natural populations and the condition of biological resources has increased steadily since the 1970's. Traditionally, genetic diversity within and among geographic areas is assessed based on a one-time sampling of...

  12. MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: functional and therapeutic implications for gene expression and the pathogenesis of hypertension

    PubMed Central

    Friese, Ryan S.; Altshuler, Angelina E.; Zhang, Kuixing; Miramontes-Gonzalez, Jose Pablo; Hightower, C. Makena; Jirout, Martin L.; Salem, Rany M.; Gayen, Jiaur R.; Mahapatra, Nitish R.; Biswas, Nilima; Cale, Mo; Vaingankar, Sucheta M.; Kim, Hyung-Suk; Courel, Maïté; Taupenot, Laurent; Ziegler, Michael G.; Schork, Nicholas J.; Pravenec, Michal; Mahata, Sushil K.; Schmid-Schönbein, Geert W.; O'Connor, Daniel T.

    2013-01-01

    Hypertension is a common hereditary syndrome with unclear pathogenesis. Chromogranin A (Chga), which catalyzes formation and cargo storage of regulated secretory granules in neuroendocrine cells, contributes to blood pressure homeostasis centrally and peripherally. Elevated Chga occurs in spontaneously hypertensive rat (SHR) adrenal glands and plasma, but central expression is unexplored. In this report, we measured SHR and Wistar–Kyoto rat (control) Chga expression in central and peripheral nervous systems, and found Chga protein to be decreased in the SHR brainstem, yet increased in the adrenal and the plasma. By re-sequencing, we systematically identified five promoter, two coding and one 3′-untranslated region (3′-UTR) polymorphism at the SHR (versus WKY or BN) Chga locus. Using HXB/BXH recombinant inbred (RI) strain linkage and correlations, we demonstrated genetic determination of Chga expression in SHR, including a cis-quantitative trait loci (QTLs) (i.e. at the Chga locus), and such expression influenced biochemical determinants of blood pressure, including a cascade of catecholamine biosynthetic enzymes, catecholamines themselves and steroids. Luciferase reporter assays demonstrated that the 3′-UTR polymorphism (which disrupts a microRNA miR-22 motif) and promoter polymorphisms altered gene expression consistent with the decline in SHR central Chga expression. Coding region polymorphisms did not account for changes in Chga expression or function. Thus, we hypothesized that the 3′-UTR and promoter mutations lead to dysregulation (diminution) of Chga in brainstem cardiovascular control nuclei, ultimately contributing to the pathogenesis of hypertension in SHR. Accordingly, we demonstrated that in vivo administration of miR-22 antagomir to SHR causes substantial (∼18 mmHg) reductions in blood pressure, opening a novel therapeutic avenue for hypertension. PMID:23674521

  13. Genomewide scan for real-word reading subphenotypes of dyslexia: Novel chromosome 13 locus and genetic complexity

    PubMed Central

    Igo, Robert P.; Chapman, Nicola H.; Berninger, Virginia W.; Matsushita, Mark; Brkanac, Zoran; Rothstein, Joseph H.; Holzman, Ted; Nielsen, Kathleen; Raskind, Wendy H.; Wijsman, Ellen M.

    2008-01-01

    Dyslexia is a common learning disability exhibited as a delay in acquiring reading skills despite adequate intelligence and instruction. Reading single real words (real-word reading, RWR) is especially impaired in many dyslexics. We performed a genome scan, using variance-components (VC) linkage analysis and Bayesian Markov chain Monte Carlo (MCMC) joint segregation and linkage analysis, for three quantitative measures of RWR in 108 multigenerational families, with followup of the strongest signals with parametric LOD score analyses. We used single-word reading efficiency (SWE) to assess speed and accuracy of RWR, and word identification (WID) to assess accuracy alone. Adjusting SWE for WID provided a third measure of RWR efficiency. All three methods of analysis identified a strong linkage signal for SWE on chromosome 13q. Based on multipoint analysis with 13 markers we obtained a MCMC intensity ratio of 53.2 (chromosome-wide p < 0.004), a VC LOD score of 2.29, and a parametric LOD score of 2.94, based on a quantitative-trait model from MCMC segregation analysis. A weaker signal for SWE on chromosome 2q occurred in the same location as a significant linkage peak seen previously in a scan for phonological decoding. MCMC oligogenic segregation analysis identified three models of transmission for WID, which could be assigned to two distinct linkage peaks on chromosomes 12 and 15. Taken together, these results indicate a locus for efficiency and accuracy of RWR on chromosome 13, and a complex model for inheritance of RWR accuracy with loci on chromosomes 12 and 15. PMID:16331673

  14. Genetics meets epigenetics: Genetic variants that modulate noncoding RNA in cardiovascular diseases.

    PubMed

    Calore, Martina; De Windt, Leon J; Rampazzo, Alessandra

    2015-12-01

    After the recent description of the human genome by the ENCODE and the FANTOM consortia, major attention has been addressed to the so-called "genomic noise", which mainly consists of noncoding RNAs (ncRNAs). Among them, microRNAs and long non-coding RNAs have been demonstrated to modulate gene expression and to be involved in several human diseases. Since ncRNAs and their targets are encoded in the genome, genetic principles apply. Common variants are supposed to influence the expression level and the functionality of ncRNAs, with subsequent differential regulation of their target genes. Moreover, several reports showed that polymorphisms in ncRNA or their target genes play a role in the development of cardiovascular adverse phenotype. Here, we provide an overview of the effects of these variations in cardiovascular diseases.

  15. Assessment of genetic diversity of zoonotic Brucella spp. recovered from livestock in Egypt using multiple locus VNTR analysis.

    PubMed

    Menshawy, Ahmed M S; Perez-Sancho, Marta; Garcia-Seco, Teresa; Hosein, Hosein I; García, Nerea; Martinez, Irene; Sayour, Ashraf E; Goyache, Joaquín; Azzam, Ragab A A; Dominguez, Lucas; Alvarez, Julio

    2014-01-01

    Brucellosis is endemic in most parts of Egypt, where it is caused mainly by Brucella melitensis biovar 3, and affects cattle and small ruminants in spite of ongoing efforts devoted to its control. Knowledge of the predominant Brucella species/strains circulating in a region is a prerequisite of a brucellosis control strategy. For this reason a study aiming at the evaluation of the phenotypic and genetic heterogeneity of a panel of 17 Brucella spp. isolates recovered from domestic ruminants (cattle, buffalo, sheep, and goat) from four governorates during a period of five years (2002-2007) was carried out using microbiological tests and molecular biology techniques (PCR, MLVA-15, and sequencing). Thirteen strains were identified as B. melitensis biovar 3 while all phenotypic and genetic techniques classified the remaining isolates as B. abortus (n = 2) and B. suis biovar 1 (n = 2). MLVA-15 yielded a high discriminatory power (h = 0.801), indicating a high genetic diversity among the B. melitensis strains circulating among domestic ruminants in Egypt. This is the first report of the isolation of B. suis from cattle in Egypt which, coupled with the finding of B. abortus, suggests a potential role of livestock as reservoirs of several zoonotic Brucella species in the region.

  16. 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

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

    PubMed Central

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

    2015-01-01

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

  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. 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.

  20. Congenic mice provide in vivo evidence for a genetic locus that modulates intrinsic transforming growth factor β1-mediated signaling and bone acquisition.

    PubMed

    Mukherjee, Aditi; Larson, Emily A; Carlos, Amy S; Belknap, John K; Rotwein, Peter; Klein, Robert F

    2012-06-01

    Osteoporosis, the most common skeletal disorder, is characterized by low bone mineral density (BMD) and an increased risk of fragility fractures. BMD is the best clinical predictor of future osteoporotic fracture risk, but is a complex trait controlled by multiple environmental and genetic determinants with individually modest effects. Quantitative trait locus (QTL) mapping is a powerful method for identifying chromosomal regions encompassing genes involved in shaping complex phenotypes, such as BMD. Here we have applied QTL analysis to male and female genetically-heterogeneous F(2) mice derived from a cross between C57BL/6 and DBA/2 strains, and have identified 11 loci contributing to femoral BMD. Further analysis of a QTL on mouse chromosome 7 following the generation of reciprocal congenic strains has allowed us to determine that the high BMD trait, which tracks with the DBA/2 chromosome and exerts equivalent effects on male and female mice, is manifested by enhanced osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro and by increased growth of metatarsal bones in short-term primary culture. An insertion/deletion DNA polymorphism in Ltbp4 exon 12 that causes the in-frame removal of 12 codons in the DBA/2-derived gene maps within 0.6 Mb of the marker most tightly linked to the QTL. LTBP4, one of four paralogous mouse proteins that modify the bioavailability of the transforming growth factor β (TGF-β) family of growth factors, is expressed in differentiating MSC-derived osteoblasts and in long bones, and reduced responsiveness to TGF-β1 is observed in MSCs of mice homozygous for the DBA/2 chromosome 7. Taken together, our results identify a potential genetic and biochemical relationship between decreased TGF-β1-mediated signaling and enhanced femoral BMD that may be regulated by a variant LTBP4 molecule.

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

    PubMed Central

    Johnson, Matthew P.; Brennecke, Shaun P.; East, Christine E.; Dyer, Thomas D.; Roten, Linda T.; Proffitt, J. Michael; Melton, Phillip E.; Fenstad, Mona H.; Aalto-Viljakainen, Tia; Mäkikallio, Kaarin; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K.; Pouta, Anneli; Kivinen, Katja; Ekholm, Eeva; Hietala, Reija; Sainio, Susanna; Saisto, Terhi; Uotila, Jukka; Klemetti, Miira; Inkeri Lokki, Anna; Georgiadis, Leena; Huovari, Elina; Kortelainen, Eija; Leminen, Satu; Lähdesmäki, Aija; Mehtälä, Susanna; Salmen, Christina

    2013-01-01

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

  2. Genetically modified crops for the bioeconomy: meeting public and regulatory expectations.

    PubMed

    Chapotin, Saharah Moon; Wolt, Jeffrey D

    2007-12-01

    As the United States moves toward a plant-based bioeconomy, a large research and development effort is focused on creating new feedstocks to meet biomass demand for biofuels, bioenergy, and specialized bioproducts, such as industrial compounds and biomaterial precursors. Most bioeconomy projections assume the widespread deployment of novel feedstocks developed through the use of modern molecular breeding techniques, but rarely consider the challenges involved with the use of genetically modified crops, which can include hurdles due to regulatory approvals, market adoption, and public acceptance. In this paper we consider the implications of various transgenic crops and traits under development for the bioeconomy that highlight these challenges. We believe that an awareness of the issues in crop and trait selection will allow developers to design crops with maximum stakeholder appeal and with the greatest potential for widespread adoption, while avoiding applications unlikely to meet regulatory approval or gain market and public acceptance.

  3. 76 FR 6623 - Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Molecular and Clinical Genetics Panel of the Medical Devices... (FDA). The meeting will be open to the public. Name of Committee: Molecular and Clinical Genetics...

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  6. The society for craniofacial genetics and developmental biology 39th annual meeting.

    PubMed

    Fish, Jennifer L; Albertson, Craig; Harris, Matthew P; Lozanoff, Scott; Marcucio, Ralph S; Richtsmeier, Joan T; Trainor, Paul A

    2017-04-01

    The Society for Craniofacial Genetics and Developmental Biology (SCGDB) aims to promote education, research, and communication, about normal and abnormal development of the tissues and organs of the head. Membership of the SCGDB is broad and diverse-including clinicians, orthodontists, scientists, and academics-but with all members sharing an interest in craniofacial biology. Each year, the SCGDB hosts a meeting where members can share their latest research, exchange ideas and resources, and build on or establish new collaborations. © 2017 Wiley Periodicals, Inc.

  7. Dissecting the genetic components of a quantitative trait locus for blood pressure and renal pathology on rat chromosome 3

    PubMed Central

    Koh-Tan, H.H. Caline; Dashti, Mohammed; Wang, Ting; Beattie, Wendy; Mcclure, John; Young, Barbara; Dominiczak, Anna F.; McBride, Martin W.; Graham, Delyth

    2017-01-01

    Background: We have previously confirmed the importance of rat chromosome 3 (RNO3) genetic loci on blood pressure elevation, pulse pressure (PP) variability and renal pathology during salt challenge in the stroke-prone spontaneously hypertensive (SHRSP) rat. The aims of this study were to generate a panel of RNO3 congenic sub-strains to genetically dissect the implicated loci and identify positional candidate genes by microarray expression profiling and analysis of next-generation sequencing data. Method and results: A panel of congenic sub-strains were generated containing Wistar–Kyoto (WKY)-introgressed segments of varying size on the SHRSP genetic background, focused within the first 50 Mbp of RNO3. Haemodynamic profiling during salt challenge demonstrated significantly reduced systolic blood pressure, diastolic blood pressure and PP variability in SP.WKYGla3a, SP.WKYGla3c, SP.WKYGla3d and SP.WKYGla3e sub-strains. Only SBP and DBP were significantly reduced during salt challenge in SP.WKYGla3b and SP.WKYGla3f sub-strains, whereas SP.WKYGla3g rats did not differ in haemodynamic response to SHRSP. Those sub-strains demonstrating significantly reduced PP variability during salt challenge also demonstrated significantly reduced renal pathology and proteinuria. Microarray expression profiling prioritized two candidate genes for blood pressure regulation (Dnm1, Tor1b), localized within the common congenic interval shared by SP.WKYGla3d and SP.WKYGla3f strains, and one candidate gene for salt-induced PP variability and renal pathology (Rabgap1), located within the region unique to the SP.WKYGla3d strain. Comparison of next-generation sequencing data identified variants within additional positional genes that are likely to affect protein function. Conclusion: This study has identified distinct intervals on RNO3-containing genes that may be important for blood pressure regulation and renal pathology during salt challenge. PMID:27755386

  8. Genetic variation at the 8q24.21 renal cancer susceptibility locus affects HIF binding to a MYC enhancer

    PubMed Central

    Grampp, Steffen; Platt, James L.; Lauer, Victoria; Salama, Rafik; Kranz, Franziska; Neumann, Viviana K.; Wach, Sven; Stöhr, Christine; Hartmann, Arndt; Eckardt, Kai-Uwe; Ratcliffe, Peter J.; Mole, David R.; Schödel, Johannes

    2016-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by loss of function of the von Hippel–Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible transcription factors (HIFs). Genetic and epigenetic determinants have an impact on HIF pathways. A recent genome-wide association study on renal cancer susceptibility identified single-nucleotide polymorphisms (SNPs) in an intergenic region located between the oncogenes MYC and PVT1. Here using assays of chromatin conformation, allele-specific chromatin immunoprecipitation and genome editing, we show that HIF binding to this regulatory element is necessary to trans-activate MYC and PVT1 expression specifically in cells of renal tubular origins. Moreover, we demonstrate that the risk-associated polymorphisms increase chromatin accessibility and activity as well as HIF binding to the enhancer. These findings provide further evidence that genetic variation at HIF-binding sites modulates the oncogenic transcriptional output of the VHL–HIF axis and provide a functional explanation for the disease-associated effects of SNPs in ccRCC. PMID:27774982

  9. The Imaging and Cognition Genetics Conference 2011, ICG 2011: A Meeting of Minds

    PubMed Central

    Le Hellard, Stéphanie; Hanson, Isabel

    2012-01-01

    In June 2011, 70 researchers from the disciplines of cognitive science, genetics, psychology, psychiatry, neurobiology, and computer science gathered in Os, Norway, for the first Imaging and Cognition Genetics meeting. The aim of the conference was to discuss progress, enhance collaboration, and maximize the sharing of resources within this new field. In this Perspective, we summarize the major themes that emerged from ICG 2011. The first is the importance of defining cognitive and imaging phenotypes and endophenotypes suitable for genetic analysis. These can come from differential psychology, cognitive science, structural MRI, tractography, and functional imaging. The second theme is the emergence of new methods for the analysis of complex traits. These include advanced computational and statistical techniques for analyzing complex datasets, and new ways of interpreting data from genome-wide association studies, such as jointly evaluating the contribution of SNPs in specific genes and pathways rather than considering single SNPs in isolation. The final theme is the importance of establishing functional correlates of newly identified genetic variants. PMID:22654732

  10. The Imaging and Cognition Genetics Conference 2011, ICG 2011: A Meeting of Minds.

    PubMed

    Le Hellard, Stéphanie; Hanson, Isabel

    2012-01-01

    In June 2011, 70 researchers from the disciplines of cognitive science, genetics, psychology, psychiatry, neurobiology, and computer science gathered in Os, Norway, for the first Imaging and Cognition Genetics meeting. The aim of the conference was to discuss progress, enhance collaboration, and maximize the sharing of resources within this new field. In this Perspective, we summarize the major themes that emerged from ICG 2011. The first is the importance of defining cognitive and imaging phenotypes and endophenotypes suitable for genetic analysis. These can come from differential psychology, cognitive science, structural MRI, tractography, and functional imaging. The second theme is the emergence of new methods for the analysis of complex traits. These include advanced computational and statistical techniques for analyzing complex datasets, and new ways of interpreting data from genome-wide association studies, such as jointly evaluating the contribution of SNPs in specific genes and pathways rather than considering single SNPs in isolation. The final theme is the importance of establishing functional correlates of newly identified genetic variants.

  11. Genetic and Molecular Characterization of Submergence Response Identifies Subtol6 as a Major Submergence Tolerance Locus in Maize

    PubMed Central

    Campbell, Malachy T.; Proctor, Christopher A.; Dou, Yongchao; Schmitz, Aaron J.; Phansak, Piyaporn; Kruger, Greg R.; Zhang, Chi; Walia, Harkamal

    2015-01-01

    Maize is highly sensitive to short term flooding and submergence. Early season flooding reduces germination, survival and growth rate of maize seedlings. We aimed to discover genetic variation for submergence tolerance in maize and elucidate the genetic basis of submergence tolerance through transcriptional profiling and linkage analysis of contrasting genotypes. A diverse set of maize nested association mapping (NAM) founder lines were screened, and two highly tolerant (Mo18W and M162W) and sensitive (B97 and B73) genotypes were identified. Tolerant lines exhibited delayed senescence and lower oxidative stress levels compared to sensitive lines. Transcriptome analysis was performed on these inbreds to provide genome level insights into the molecular responses to submergence. Tolerant lines had higher transcript abundance of several fermentation-related genes and an unannotated Pyrophosphate-Dependent Fructose-6-Phosphate 1-Phosphotransferase gene during submergence. A coexpression network enriched for CBF (C-REPEAT/DRE BINDING FACTOR: C-REPEAT/DRE BINDING FACTOR) genes, was induced by submergence in all four inbreds, but was more activated in the tolerant Mo18W. A recombinant inbred line (RIL) population derived from Mo18W and B73 was screened for submergence tolerance. A major QTL named Subtol6 was mapped to chromosome 6 that explains 22% of the phenotypic variation within the RIL population. We identified two candidate genes (HEMOGLOBIN2 and RAV1) underlying Subtol6 based on contrasting expression patterns observed in B73 and Mo18W. Sources of tolerance identified in this study (Subtol6) can be useful to increase survival rate during flooding events that are predicted to increase in frequency with climate change. PMID:25806518

  12. Genetic diversity patterns in the SR-BI/II locus can be explained by a recent selective sweep.

    PubMed

    Le Jossec, Mireille; Wambach, Tina; Labuda, Damian; Sinnett, Daniel; Levy, Emile

    2004-04-01

    The human scavenger receptor class B type I (SR-BI and splice variant SR-BII) plays a central role in HDL cholesterol metabolism and represents a candidate gene for a number of related diseases. We examined the genetic diversity of its coding and flanking regions in a sample of 178 chromosomes from individuals of European, African, East Asian (including Southeast Asian), Middle-Eastern as well as Amerindian descent. Nine of the 14 polymorphisms observed are new. Four of the five variants causing amino acid replacements, G2S, S229G, R484W, and G499R, are likely to affect protein structure and function. SR-BI/BII diversity is partitioned among 19 haplotypes; all but one interconnected by single mutation or a recombination event. Such tight haplotype network and the unusual geographic partitioning of this diversity, high not only in Africa but in East Asia as well, suggests its recent origin and possible effect of selection. Coalescent analysis infers a relatively short time to the most recent common ancestor and points to population expansion in Africa and East Asia. These two continents differ significantly in pairwise F(ST) values, differing as well from a single cluster formed by Europe, Middle East and America. In the context of findings for similarly analyzed other loci, we propose that a selective sweep at the origin of modern human populations could explain the low level of ancestral SR-BI/II diversity. The unusually deep split between Africa and Asia, well beyond the Upper Paleolithic when inferred under neutrality, is consistent with subsequent geographical and demographic expansion favoring the accumulation of new variants, especially in groups characterized by large effective population sizes, such as Asians and Africans. The relevance of such partitioning of SR-BI/II diversity remains to be investigated in genetic epidemiological studies which can be guided by the present findings.

  13. Amplification of a single-locus variable-number direct repeats with restriction fragment length polymorphism (DR-PCR/RFLP) for genetic typing of Acinetobacter baumannii strains.

    PubMed

    Nowak-Zaleska, Alicja; Krawczyk, Beata; Kotłowski, Roman; Mikucka, Agnieszka; Gospodarek, Eugenia

    2008-01-01

    In search of an effective DNA typing technique for Acinetobacter baumannii strains for hospital epidemiology use, the performance and convenience of a new target sequence was evaluated. Using known genomic sequences of Acinetobacter baumannii strains AR 319754 and ATCC 17978, we developed single-locus variable-number direct-repeat analysis using polymerase chain reaction-restriction fragment length polymorphism (DR-PCR/RFLP) method. A total of 90 Acinetobacter baumannii strains isolated from patients of the Clinical Hospital in Bydgoszcz, Poland, were examined. Initially, all strains were typed using macrorestriction analysis of the chromosomal DNA by pulsed-field gel electrophoresis (REA-PFGE). Digestion of the chromosomal DNA with the ApaI endonuclease and separation of the fragments by PFGE revealed 21 unique types. Application of DR-PCR/RFLP resulted in recognition of 12 clusters. The results showed that the DR-PCR/RFLP method is less discriminatory than REA-PFGE, however, the novel genotyping method can be used as an alternative technique for generating DNA profiles in epidemiological studies of intra-species genetic relatedness of Acinetobacter baumannii strains.

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

    PubMed Central

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

    2014-01-01

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

  15. Quantitative genetic bases of anthocyanin variation in grape (Vitis vinifera L. ssp. sativa) berry: a quantitative trait locus to quantitative trait nucleotide integrated study.

    PubMed

    Fournier-Level, Alexandre; Le Cunff, Loïc; Gomez, Camila; Doligez, Agnès; Ageorges, Agnès; Roux, Catherine; Bertrand, Yves; Souquet, Jean-Marc; Cheynier, Véronique; This, Patrice

    2009-11-01

    The combination of QTL mapping studies of synthetic lines and association mapping studies of natural diversity represents an opportunity to throw light on the genetically based variation of quantitative traits. With the positional information provided through quantitative trait locus (QTL) mapping, which often leads to wide intervals encompassing numerous genes, it is now feasible to directly target candidate genes that are likely to be responsible for the observed variation in completely sequenced genomes and to test their effects through association genetics. This approach was performed in grape, a newly sequenced genome, to decipher the genetic architecture of anthocyanin content. Grapes may be either white or colored, ranging from the lightest pink to the darkest purple tones according to the amount of anthocyanin accumulated in the berry skin, which is a crucial trait for both wine quality and human nutrition. Although the determinism of the white phenotype has been fully identified, the genetic bases of the quantitative variation of anthocyanin content in berry skin remain unclear. A single QTL responsible for up to 62% of the variation in the anthocyanin content was mapped on a Syrah x Grenache F(1) pseudo-testcross. Among the 68 unigenes identified in the grape genome within the QTL interval, a cluster of four Myb-type genes was selected on the basis of physiological evidence (VvMybA1, VvMybA2, VvMybA3, and VvMybA4). From a core collection of natural resources (141 individuals), 32 polymorphisms revealed significant association, and extended linkage disequilibrium was observed. Using a multivariate regression method, we demonstrated that five polymorphisms in VvMybA genes except VvMybA4 (one retrotransposon, three single nucleotide polymorphisms and one 2-bp insertion/deletion) accounted for 84% of the observed variation. All these polymorphisms led to either structural changes in the MYB proteins or differences in the VvMybAs promoters. We concluded that

  16. A genetic network of flowering-time genes in wheat leaves, in which an APETALA1/FRUITFULL-like gene, VRN1, is upstream of FLOWERING LOCUS T.

    PubMed

    Shimada, Sanae; Ogawa, Taiichi; Kitagawa, Satoshi; Suzuki, Takayuki; Ikari, Chihiro; Shitsukawa, Naoki; Abe, Tomoko; Kawahigashi, Hiroyuki; Kikuchi, Rie; Handa, Hirokazu; Murai, Koji

    2009-05-01

    To elucidate the genetic mechanism of flowering in wheat, we performed expression, mutant and transgenic studies of flowering-time genes. A diurnal expression analysis revealed that a flowering activator VRN1, an APETALA1/FRUITFULL homolog in wheat, was expressed in a rhythmic manner in leaves under both long-day (LD) and short-day (SD) conditions. Under LD conditions, the upregulation of VRN1 during the light period was followed by the accumulation of FLOWERING LOCUS T (FT) transcripts. Furthermore, FT was not expressed in a maintained vegetative phase (mvp) mutant of einkorn wheat (Triticum monococcum), which has null alleles of VRN1, and never transits from the vegetative to the reproductive phase. These results suggest that VRN1 is upstream of FT and upregulates the FT expression under LD conditions. The overexpression of FT in a transgenic bread wheat (Triticum aestivum) caused extremely early heading with the upregulation of VRN1 and the downregulation of VRN2, a putative repressor gene of VRN1. These results suggest that in the transgenic plant, FT suppresses VRN2 expression, leading to an increase in VRN1 expression. Based on these results, we present a model for a genetic network of flowering-time genes in wheat leaves, in which VRN1 is upstream of FT with a positive feedback loop through VRN2. The mvp mutant has a null allele of VRN2, as well as of VRN1, because it was obtained from a spring einkorn wheat strain lacking VRN2. The fact that FT is not expressed in the mvp mutant supports the present model.

  17. A genetic network of flowering-time genes in wheat leaves, in which an APETALA1/FRUITFULL-like gene, VRN1, is upstream of FLOWERING LOCUS T

    PubMed Central

    Shimada, Sanae; Ogawa, Taiichi; Kitagawa, Satoshi; Suzuki, Takayuki; Ikari, Chihiro; Shitsukawa, Naoki; Abe, Tomoko; Kawahigashi, Hiroyuki; Kikuchi, Rie; Handa, Hirokazu; Murai, Koji

    2009-01-01

    To elucidate the genetic mechanism of flowering in wheat, we performed expression, mutant and transgenic studies of flowering-time genes. A diurnal expression analysis revealed that a flowering activator VRN1, an APETALA1/FRUITFULL homolog in wheat, was expressed in a rhythmic manner in leaves under both long-day (LD) and short-day (SD) conditions. Under LD conditions, the upregulation of VRN1 during the light period was followed by the accumulation of FLOWERING LOCUS T (FT) transcripts. Furthermore, FT was not expressed in a maintained vegetative phase (mvp) mutant of einkorn wheat (Triticum monococcum), which has null alleles of VRN1, and never transits from the vegetative to the reproductive phase. These results suggest that VRN1 is upstream of FT and upregulates the FT expression under LD conditions. The overexpression of FT in a transgenic bread wheat (Triticum aestivum) caused extremely early heading with the upregulation of VRN1 and the downregulation of VRN2, a putative repressor gene of VRN1. These results suggest that in the transgenic plant, FT suppresses VRN2 expression, leading to an increase in VRN1 expression. Based on these results, we present a model for a genetic network of flowering-time genes in wheat leaves, in which VRN1 is upstream of FT with a positive feedback loop through VRN2. The mvp mutant has a null allele of VRN2, as well as of VRN1, because it was obtained from a spring einkorn wheat strain lacking VRN2. The fact that FT is not expressed in the mvp mutant supports the present model. PMID:19175767

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

    PubMed

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

    2008-02-01

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

  19. Genetic analysis of the recG locus of Escherichia coli K-12 and of its role in recombination and DNA repair.

    PubMed Central

    Lloyd, R G; Buckman, C

    1991-01-01

    We describe a transposon insertion that reduces the efficiency of homologous recombination and DNA repair in Escherichia coli. The insertion, rec-258, was located between pyrE and dgo at min 82.1 on the current linkage map. On the basis of linkage to pyrE and complementation studies with the cloned rec+ gene, rec-258 was identified as an allele of the recG locus first reported by Storm et al. (P. K. Storm, W. P. M. Hoekstra, P. G. De Haan, and C. Verhoef, Mutat. Res. 13:9-17, 1971). The recG258 mutation confers sensitivity to mitomycin C and UV light and a 3- to 10-fold deficiency in conjugational recombination in wild-type, recB recC sbcA, and recB recC sbcB sbcC genetic backgrounds. It does not appear to affect plasmid recombination in the wild-type. A recG258 single mutant is also sensitive to ionizing radiation. The SOS response is induced normally, although the basal level of expression is elevated two- to threefold. Further genetic studies revealed that recB recG and recG recJ double mutants are much more sensitive to UV light than the respective single mutants in each case. However, no synergistic interactions were discovered between recG258 and mutations in recF, recN, or recQ. It is concluded that recG does not fall within any of the accepted groups of genes that affect recombination and DNA repair. PMID:1846849

  20. Post-Zygotic and Inter-Individual Structural Genetic Variation in a Presumptive Enhancer Element of the Locus between the IL10Rβ and IFNAR1 Genes

    PubMed Central

    Prakash, Kancherla Reddy; Przerada, Szymon; Paprocka, Hanna; Zywicka, Anna; Westerman, Maxwell P.; Pedersen, Nancy L.; O'Hanlon, Terrance P.; Rider, Lisa G.; Miller, Frederick W.; Srutek, Ewa; Jankowski, Michal; Zegarski, Wojciech; Piotrowski, Arkadiusz; Absher, Devin; Dumanski, Jan P.

    2013-01-01

    Although historically considered as junk-DNA, tandemly repeated sequence motifs can affect human phenotype. For example, variable number tandem repeats (VNTR) with embedded enhancers have been shown to regulate gene transcription. The post-zygotic variation is the presence of genetically distinct populations of cells in an individual derived from a single zygote, and this is an understudied aspect of genome biology. We report somatically variable VNTR with sequence properties of an enhancer, located upstream of IFNAR1. Initially, SNP genotyping of 63 monozygotic twin pairs and multiple tissues from 21 breast cancer patients suggested a frequent post-zygotic mosaicism. The VNTR displayed a repeated 32 bp core motif in the center of the repeat, which was flanked by similar variable motifs. A total of 14 alleles were characterized based on combinations of segments, which showed post-zygotic and inter-individual variation, with up to 6 alleles in a single subject. Somatic variation occurred in ∼24% of cases. In this hypervariable region, we found a clustering of transcription factor binding sites with strongest sequence similarity to mouse Foxg1 transcription factor binding motif. This study describes a VNTR with sequence properties of an enhancer that displays post-zygotic and inter-individual genetic variation. This element is within a locus containing four related cytokine receptors: IFNAR2, IL10Rβ, IFNAR1 and IFNGR2, and we hypothesize that it might function in transcriptional regulation of several genes in this cluster. Our findings add another level of complexity to the variation among VNTR-based enhancers. Further work may unveil the normal function of this VNTR in transcriptional control and its possible involvement in diseases connected with these receptors, such as autoimmune conditions and cancer. PMID:24023707

  1. Genetic basis for the psychostimulant effects of nicotine: a quantitative trait locus analysis in AcB/BcA recombinant congenic mice.

    PubMed

    Gill, K J; Boyle, A E

    2005-10-01

    Genetic differences in sensitivity to nicotine have been reported in both animals and humans. The present study utilized a novel methodology to map genes involved in regulating both the psychostimulant and depressant effects of nicotine in the AcB/BcA recombinant congenic strains (RCS) of mice. Locomotor activity was measured in a computerized open-field apparatus following subcutaneous administration of saline (days 1 and 2) or nicotine on day 3. The phenotypic measures obtained from this experimental design included total basal locomotor activity, as well as total nicotine activity, nicotine difference scores, nicotine percent change and nicotine regression residual scores. The results indicated that the C57BL/6J (B6) were insensitive to nicotine over the entire dose-response curve (0.1, 0.2, 0.4 and 0.8 mg/kg). However, the 0.8-mg/kg dose of nicotine produced a significant decrease in the locomotor activity in the A/J strain and a wide and continuous range of both locomotor excitation and depression among the AcB/BcA RCS. Single-locus association analysis in the AcB RCS identified quantitative trait loci (QTL) for the psychostimulant effects of nicotine on chromosomes 11, 12, 13, 14 and 17 and one QTL for nicotine-induced depression on chromosome 11. In the BcA RCS, nicotine-induced locomotor activation was associated with seven putative regions on chromosomes 2, 7, 8, 13, 14, 16 and 17. There were no overlapping QTL and no genetic correlations between saline- and nicotine-related phenotypes in the AcB/BcA RCS. A number of putative candidate genes were in proximity to regions identified with nicotine sensitivity, including the alpha2 subunit of the nicotinic acetylcholine receptor and the dopamine D3 receptor.

  2. Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions.

    PubMed

    Pinel, Philippe; Fauchereau, Fabien; Moreno, Antonio; Barbot, Alexis; Lathrop, Mark; Zelenika, Diana; Le Bihan, Denis; Poline, Jean-Baptiste; Bourgeron, Thomas; Dehaene, Stanislas

    2012-01-18

    Recent advances have been made in the genetics of two human communication skills: speaking and reading. Mutations of the FOXP2 gene cause a severe form of language impairment and orofacial dyspraxia, while single-nucleotide polymorphisms (SNPs) located within a KIAA0319/TTRAP/THEM2 gene cluster and affecting the KIAA0319 gene expression are associated with reading disability. Neuroimaging studies of clinical populations point to partially distinct cerebral bases for language and reading impairments. However, alteration of FOXP2 and KIAA0319/TTRAP/THEM2 polymorphisms on typically developed language networks has never been explored. Here, we genotyped and scanned 94 healthy subjects using fMRI during a reading task. We studied the correlation of genetic polymorphisms with interindividual variability in brain activation and functional asymmetry in frontal and temporal cortices. In FOXP2, SNPs rs6980093 and rs7799109 were associated with variations of activation in the left frontal cortex. In the KIAA0319/TTRAP/THEM2 locus, rs17243157 was associated with asymmetry in functional activation of the superior temporal sulcus (STS). Interestingly, healthy subjects bearing the KIAA0319/TTRAP/THEM2 variants previously identified as enhancing the risk of dyslexia showed a reduced left-hemispheric asymmetry of the STS. Our results confirm that both FOXP2 and KIAA0319/TTRAP/THEM2 genes play an important role in human language development, but probably through different cerebral pathways. The observed cortical effects mirror previous fMRI results in developmental language and reading disorders, and suggest that a continuum may exist between these pathologies and normal interindividual variability.

  3. Multi-locus genotypes of Enterocytozoon bieneusi in captive Asiatic black bears in southwestern China: High genetic diversity, broad host range, and zoonotic potential

    PubMed Central

    Cao, Xuefeng; Song, Yuan; Wang, Wuyou; Huang, Xiangming; Liu, Xuehan; Hu, Yanchun; Fu, Hualin; He, Min; Wang, Ya; Zhang, Yue; Wu, Kongju; Peng, Guangneng

    2017-01-01

    Enterocytozoon bieneusi is an obligate eukaryotic intracellular parasite that infects a wide variety of vertebrate and invertebrate hosts. Although considerable research has been conducted on this organism, relatively little information is available on the occurrence of E. bieneusi in captive Asiatic black bears. The present study was performed to determine the prevalence, genetic diversity, and zoonotic potential of E. bieneusi in captive Asiatic black bears in zoos in southwestern China. Fecal specimens from Asiatic black bears in four zoos, located in four different cities, were collected and analyzed for the prevalence of E. bieneusi. The average prevalence of E. bieneusi was 27.4% (29/106), with the highest prevalence in Guiyang Zoo (36.4%, 16/44). Altogether, five genotypes of E. bieneusi were identified among the 29 E. bieneusi-positive samples, including three known genotypes (CHB1, SC02, and horse2) and two novel genotypes named ABB1 and ABB2. Multi-locus sequence typing using three microsatellites (MS1, MS3, and MS7) and one minisatellite (MS4) revealed V, III, V, and IV genotypes at these four loci, respectively. Phylogenetic analysis showed that the genotypes SC02 and ABB2 were clustered into group 1 of zoonotic potential, the genotypes CHB1 and ABB1 were clustered into a new group, and the genotype horse2 was clustered into group 6 of unclear zoonotic potential. In conclusion, this study identified two novel E. bieneusi genotypes in captive Asiatic black bears, and used microsatellite and minisatellite markers to reveal E. bieneusi genetic diversity. Moreover, our findings show that genotypes SC02 (identified in humans) and ABB2 belong to group 1 with zoonotic potential, suggesting the risk of transmission of E. bieneusi from Asiatic black bears to humans and other animals. PMID:28182656

  4. Genetic Susceptible Locus in NOTCH2 Interacts with Arsenic in Drinking Water on Risk of Type 2 Diabetes

    PubMed Central

    Pan, Wen-Chi; Kile, Molly L.; Seow, Wei Jie; Lin, Xihong; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Lu, Quan; Christiani, David C.

    2013-01-01

    Background Chronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear. Objectives This study evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes associated with diabetes and arsenic exposure in drinking water on the risk of developing T2DM. Methods In 2009–2011, we conducted a follow up study of 957 Bangladeshi adults who participated in a case-control study of arsenic-induced skin lesions in 2001–2003. Logistic regression models were used to evaluate the association between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up. Arsenic exposure was characterized by drinking water samples collected from participants' tubewells. False discovery rates were applied in the analysis to control for multiple comparisons. Results Median arsenic levels in 2001–2003 were higher among diabetic participants compared with non-diabetic ones (71.6 µg/L vs. 12.5 µg/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally associated with increased risk of T2DM (rs17070905, Odds Ratio (OR)  = 2.30, 95% confidence interval (CI) 1.17–4.50; rs17070967, OR = 2.02, 95%CI 1.00–4.06; rs6766801, OR = 2.33, 95%CI 1.18–4.60), but these associations did not reach the statistical significance after adjusting for multiple comparisons. A significant interaction between arsenic and NOTCH2 (rs699780) was observed which significantly increased the risk of T2DM (p for interaction = 0.003; q-value = 0.021). Further restricted analysis among participants exposed to water arsenic of less than 148 µg/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction  = 0.048; q-value = 0.004). Conclusions These findings suggest that genetic variation in NOTCH2 increased

  5. Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis.

    PubMed Central

    Meling, G. I.; Lothe, R. A.; Børresen, A. L.; Hauge, S.; Graue, C.; Clausen, O. P.; Rognum, T. O.

    1991-01-01

    Alterations within the retinoblastoma (Rb) gene, as detected by the VNTR probe p68RS2.0, and flow cytometric DNA pattern have been analysed in 255 colorectal carcinomas. A total of 35.3% of the tumours had alterations within the Rb gene. Amplification of one allele was demonstrated in 29.5% of the tumours, and loss of heterozygosity was found in 11.5%. No association was found between amplification within the Rb gene and clinicopathological characteristics of the patients. The high frequency of alterations demonstrated within the Rb gene, suggests that this gene is involved in colorectal carcinogenesis with amplification as by far the most abundant genetic alteration. This may imply that the Rb gene has an oncogene-like function in colorectal carcinomas, rather than acting as a tumour suppressor gene. Sixty-three per cent of the carcinomas were DNA aneuploid, and a significant association was demonstrated between amplification within the Rb gene and DNA aneuploidy (P less than 0.01). Two other chromosome loci were analysed, on chromosome 1p (probe pYNZ2) and on chromosome 2p (probe pYNH24), respectively. On chromosome 1p, heterozygous loss was found in 22.2% of the tumours, indicating an involvement of this chromosome in a subset of colorectal carcinomas. Images Figure 1 PMID:1911187

  6. Hybrid Incompatibility in Arabidopsis Is Determined by a Multiple-Locus Genetic Network1[W][OA

    PubMed Central

    Burkart-Waco, Diana; Josefsson, Caroline; Dilkes, Brian; Kozloff, Nora; Torjek, Otto; Meyer, Rhonda; Altmann, Thomas; Comai, Luca

    2012-01-01

    The cross between Arabidopsis thaliana and the closely related species Arabidopsis arenosa results in postzygotic hybrid incompatibility, manifested as seed death. Ecotypes of A. thaliana were tested for their ability to produce live seed when crossed to A. arenosa. The identified genetic variation was used to map quantitative trait loci (QTLs) encoded by the A. thaliana genome that affect the frequency of postzygotic lethality and the phenotypes of surviving seeds. Seven QTLs affecting the A. thaliana component of this hybrid incompatibility were identified by crossing a Columbia × C24 recombinant inbred line population to diploid A. arenosa pollen donors. Additional epistatic loci were identified based on their pairwise interaction with one or several of these QTLs. Epistatic interactions were detected for all seven QTLs. The two largest additive QTLs were subjected to fine-mapping, indicating the action of at least two genes in each. The topology of this network reveals a large set of minor-effect loci from the maternal genome controlling hybrid growth and viability at different developmental stages. Our study establishes a framework that will enable the identification and characterization of genes and pathways in A. thaliana responsible for hybrid lethality in the A. thaliana × A. arenosa interspecific cross. PMID:22135429

  7. The effects of locus number, genetic divergence, and genotyping error on the utility of dominant markers for hybrid identification

    PubMed Central

    Sovic, Michael G; Kubatko, Laura S; Fuerst, Paul A

    2014-01-01

    In surveys of hybrid zones, dominant genetic markers are often used to identify individuals of hybrid origin and assign these individuals to one of several potential hybrid classes. Quantitative analyses that address the statistical power of dominant markers in such inference are scarce. In this study, dominant genotype data were simulated to evaluate the effects of, first, the number of loci analyzed, second, the magnitude of differentiation between the markers scored in the groups that are hybridizing, and third, the level of genotyping error associated with the data when assigning individuals to various parental and hybrid categories. The overall performance of the assignment methods was relatively modest at the lowest level of divergence examined (Fst ˜ 0.4), but improved substantially at higher levels of differentiation (Fst ˜ 0.67 or 0.8). The effect of genotyping error was dependent on the level of divergence between parental taxa, with larger divergences tempering the effects of genotyping error. These results highlight the importance of considering the effects of each of the variables when assigning individuals to various parental and hybrid categories, and can help guide decisions regarding the number of loci employed in future hybridization studies to achieve the power and level of resolution desired. PMID:24634730

  8. Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence for genetic heterogeneity

    SciTech Connect

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

    1995-11-20

    Primary congenital glaucoma (GLC3) is an inherited eye disorder that accounts for 0.01-0.04% of total blindness. Although a large number of chromosomal abnormalities have already been reported in patients with congenital glaucoma, the precise location and pathogenesis of this condition remain elusive. By using a group of 17 GLC3 families and a combination of both candidate regional and general positional mapping strategies, we have mapped a locus for GLC3 to the short arm of chromosome 2. Eleven families showed no recombination with 3 tightly linked markers of D2S177 (Z = 9.40), D2S1346 (Z = 8.83), and D2S1348 (Z = 8.90) with a combined haplotype lod score of 11.50. Haplotype and multipoint linkage analyses of 14 DNA markers from 2p indicated that the disease gene is located in the 2p21 region and is flanked by DNA markers D2S1788/D2S1325 ({theta} = 0.03; Z = 5.42) and D2S1356 ({theta} = 0.05; Z = 4.69). Inspection of haplotype and heterogeneity analysis confirmed that 6 families are not linked to the 2p21 region, thus providing the first proof of genetic heterogeneity for this phenotype. We therefore designated the locus on 2p21 GLC3A and positioned it in the overall linkage map of Tel-D2S405-D2S367-(D2S1788/D2S1325)-[(GLC 3A,D2S177)/(D2S1346/D2S1348)]-D2S1356-D2S119-D2S1761-D2S1248-D2S1352-D2S406-D2S441-Cen. Of the seven genes mapping to the 2p21 region, CAD, CALM2, and LHCGR are centromeric to D2S119 and can be excluded as a candidate for GLC3A, but mutations in PRK-R, TIK, SOS1, or SPTBN1 may still be accountable for this phenotype. As human 2p21 shows homology with mouse chromosomes 11 and 17, the homolog of GLC3A is expected to reside on one of these two chromosomes. 36 refs., 3 figs., 5 tabs.

  9. Genetic variation at the CELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity.

    PubMed

    Hinney, Anke; Albayrak, Ozgür; Antel, Jochen; Volckmar, Anna-Lena; Sims, Rebecca; Chapman, Jade; Harold, Denise; Gerrish, Amy; Heid, Iris M; Winkler, Thomas W; Scherag, André; Wiltfang, Jens; Williams, Julie; Hebebrand, Johannes

    2014-06-01

    Deviations from normal body weight are observed prior to and after the onset of Alzheimer's disease (AD). Midlife obesity confers increased AD risk in later life, whereas late-life obesity is associated with decreased AD risk. The role of underweight and weight loss for AD risk is controversial. Based on the hypothesis of shared genetic variants for both obesity and AD, we analyzed the variants identified for AD or obesity from genome-wide association meta-analyses of the GERAD (AD, cases = 6,688, controls = 13,685) and GIANT (body mass index [BMI] as measure of obesity, n = 123,865) consortia. Our cross-disorder analysis of genome-wide significant 39 obesity SNPs and 23 AD SNPs in these two large data sets revealed that: (1) The AD SNP rs10838725 (pAD  = 1.1 × 10(-08)) at the locus CELF1 is also genome-wide significant for obesity (pBMI  = 7.35 × 10(-09) ). (2) Four additional AD risk SNPs were nominally associated with obesity (rs17125944 at FERMT2, pBMI  = 4.03 × 10(-05), pBMI corr  = 2.50 × 10(-03) ; rs3851179 at PICALM; pBMI  = 0.002, rs2075650 at TOMM40/APOE, pBMI  = 0.024, rs3865444 at CD33, pBMI  = 0.024). (3) SNPs at two of the obesity risk loci (rs4836133 downstream of ZNF608; pAD  = 0.002 and at rs713586 downstream of RBJ/DNAJC27; pAD  = 0.018) were nominally associated with AD risk. Additionally, among the SNPs used for confirmation in both studies the AD risk allele of rs1858973, with an AD association just below genome-wide significance (pAD  = 7.20 × 10(-07)), was also associated with obesity (SNP at IQCK/GPRC5B; pBMI  = 5.21 × 10(-06) ; pcorr  = 3.24 × 10(-04)). Our first GWAS based cross-disorder analysis for AD and obesity suggests that rs10838725 at the locus CELF1 might be relevant for both disorders.

  10. Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

    PubMed Central

    Nijmeijer, Rian M.; Schaap, Frank G.; Smits, Alexander J. J.; Kremer, Andreas E.; Akkermans, Louis M. A.; Kroese, Alfons B. A.; Rijkers, Ger. T.; Schipper, Marguerite E. I.; Verheem, André; Wijmenga, Cisca; Gooszen, Hein G.; van Erpecum, Karel J.

    2014-01-01

    Background Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs including the pancreas, exhibits anti-inflammatory effects by inhibiting NF-κB activation and is implicated in maintaining intestinal barrier integrity and preventing bacterial overgrowth and translocation. Here we explore, with the aid of complementary animal and human experiments, the potential role of FXR in acute pancreatitis. Methods Experimental acute pancreatitis was induced using the CCK-analogue cerulein in wild-type and Fxr-/- mice. Severity of acute pancreatitis was assessed using histology and a semi-quantitative scoring system. Ileal permeability was analyzed in vitro by Ussing chambers and an in vivo permeability assay. Gene expression of Fxr and Fxr target genes was studied by quantitative RT-PCR. Serum FGF19 levels were determined by ELISA in acute pancreatitis patients and healthy volunteers. A genetic association study in 387 acute pancreatitis patients and 853 controls was performed using 9 tagging single nucleotide polymorphisms (SNPs) covering the complete FXR gene and two additional functional SNPs. Results In wild-type mice with acute pancreatitis, ileal transepithelial resistance was reduced and ileal mRNA expression of Fxr target genes Fgf15, SHP, and IBABP was decreased. Nevertheless, Fxr-/- mice did not exhibit a more severe acute pancreatitis than wild-type mice. In patients with acute pancreatitis, FGF19 levels were lower than in controls. However, there were no associations of FXR SNPs or haplotypes with susceptibility to acute pancreatitis, or its course, outcome or etiology. Conclusion We found no evidence for a major role of FXR in acute human or murine pancreatitis. The observed altered Fxr activity during the course of disease may be a

  11. Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders.

    PubMed

    Usdin, Karen; Hayward, Bruce E; Kumari, Daman; Lokanga, Rachel A; Sciascia, Nicholas; Zhao, Xiao-Nan

    2014-01-01

    The Fragile X-related disorders are a group of genetic conditions that include the neurodegenerative disorder, Fragile X-associated tremor/ataxia syndrome (FXTAS), the fertility disorder, Fragile X-associated primary ovarian insufficiency (FXPOI) and the intellectual disability, Fragile X syndrome (FXS). The pathology in all these diseases is related to the number of CGG/CCG-repeats in the 5' UTR of the Fragile X mental retardation 1 (FMR1) gene. The repeats are prone to continuous expansion and the increase in repeat number has paradoxical effects on gene expression increasing transcription on mid-sized alleles and decreasing it on longer ones. In some cases the repeats can simultaneously both increase FMR1 mRNA production and decrease the levels of the FMR1 gene product, Fragile X mental retardation 1 protein (FMRP). Since FXTAS and FXPOI result from the deleterious consequences of the expression of elevated levels of FMR1 mRNA and FXS is caused by an FMRP deficiency, the clinical picture is turning out to be more complex than once appreciated. Added complications result from the fact that increasing repeat numbers make the alleles somatically unstable. Thus many individuals have a complex mixture of different sized alleles in different cells. Furthermore, it has become apparent that the eponymous fragile site, once thought to be no more than a useful diagnostic criterion, may have clinical consequences for females who inherit chromosomes that express this site. This review will cover what is currently known about the mechanisms responsible for repeat instability, for the repeat-mediated epigenetic changes that affect expression of the FMR1 gene, and for chromosome fragility. It will also touch on what current and future options are for ameliorating some of these effects.

  12. Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders

    PubMed Central

    Usdin, Karen; Hayward, Bruce E.; Kumari, Daman; Lokanga, Rachel A.; Sciascia, Nicholas; Zhao, Xiao-Nan

    2014-01-01

    The Fragile X-related disorders are a group of genetic conditions that include the neurodegenerative disorder, Fragile X-associated tremor/ataxia syndrome (FXTAS), the fertility disorder, Fragile X-associated primary ovarian insufficiency (FXPOI) and the intellectual disability, Fragile X syndrome (FXS). The pathology in all these diseases is related to the number of CGG/CCG-repeats in the 5′ UTR of the Fragile X mental retardation 1 (FMR1) gene. The repeats are prone to continuous expansion and the increase in repeat number has paradoxical effects on gene expression increasing transcription on mid-sized alleles and decreasing it on longer ones. In some cases the repeats can simultaneously both increase FMR1 mRNA production and decrease the levels of the FMR1 gene product, Fragile X mental retardation 1 protein (FMRP). Since FXTAS and FXPOI result from the deleterious consequences of the expression of elevated levels of FMR1 mRNA and FXS is caused by an FMRP deficiency, the clinical picture is turning out to be more complex than once appreciated. Added complications result from the fact that increasing repeat numbers make the alleles somatically unstable. Thus many individuals have a complex mixture of different sized alleles in different cells. Furthermore, it has become apparent that the eponymous fragile site, once thought to be no more than a useful diagnostic criterion, may have clinical consequences for females who inherit chromosomes that express this site. This review will cover what is currently known about the mechanisms responsible for repeat instability, for the repeat-mediated epigenetic changes that affect expression of the FMR1 gene, and for chromosome fragility. It will also touch on what current and future options are for ameliorating some of these effects. PMID:25101111

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

    SciTech Connect

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

    1994-09-01

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

  14. Identification and characterization of a NaCl-responsive genetic locus involved in survival during desiccation in Sinorhizobium meliloti.

    PubMed

    Vriezen, Jan A C; de Bruijn, Frans J; Nüsslein, Klaus

    2013-09-01

    The Rhizobiaceae are a bacterial family of enormous agricultural importance due to the ability of its members to fix atmospheric nitrogen in an intimate relationship with plants. Their survival as naturally occurring soil bacteria in agricultural soils as well as popular seed inocula is affected directly by drought and salinity. Survival after desiccation in the presence of NaCl is enabled by underlying genetic mechanisms in the model organism Sinorhizobium meliloti 1021. Since salt stress parallels a loss in water activity, the identification of NaCl-responsive loci may identify loci involved in survival during desiccation. This approach enabled identification of the loci asnO and ngg by their reduced ability to grow on increased NaCl concentrations, likely due to their inability to produce the osmoprotectant N-acetylglutaminylglutamine (NAGGN). In addition, the mutant harboring ngg::Tn5luxAB was affected in its ability to survive desiccation and responded to osmotic stress. The desiccation sensitivity may have been due to secondary functions of Ngg (N-acetylglutaminylglutamine synthetase)-like cell wall metabolism as suggested by the presence of a d-alanine-d-alanine ligase (dAla-dAla) domain and by sensitivity of the mutant to β-lactam antibiotics. asnO::Tn5luxAB is expressed during the stationary phase under normal growth conditions. Amino acid sequence similarity to enzymes producing β-lactam inhibitors and increased resistance to β-lactam antibiotics may indicate that asnO is involved in the production of a β-lactam inhibitor.

  15. Meeting Report: International Symposium on the Genetics of Aging and Life History II

    PubMed Central

    Lee, Seung‐Jae V.; Nam, Hong Gil

    2015-01-01

    The second International Symposium on the Genetics of Aging and Life History was held at the campus of Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, South Korea, from May 14 to 16, 2014. Many leading scientists in the field of aging research from all over the world contributed to the symposium by attending and presenting their recent work and thoughts. The aim of the symposium was to stimulate international collaborations and interactions among scientists who work on the biology of aging. In the symposium, the most recent and exciting work on aging research was presented, covering a wide range of topics, including the genetics of aging, age‐associated diseases, and cellular senescence. The work was conducted in various organisms, including C. elegans, mice, plants, and humans. Topics covered in the symposium stimulated discussion of novel directions for future research on aging. The meeting ended with a commitment for the third International Symposium on the Genetics of Aging and Life History, which will be held in 2016. PMID:26115541

  16. Meeting Report: International Symposium on the Genetics of Aging and Life History II.

    PubMed

    Artan, Murat; Hwang, Ara B; Lee, Seung V; Nam, Hong Gil

    2015-06-01

    The second International Symposium on the Genetics of Aging and Life History was held at the campus of Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, South Korea, from May 14 to 16, 2014. Many leading scientists in the field of aging research from all over the world contributed to the symposium by attending and presenting their recent work and thoughts. The aim of the symposium was to stimulate international collaborations and interactions among scientists who work on the biology of aging. In the symposium, the most recent and exciting work on aging research was presented, covering a wide range of topics, including the genetics of aging, age-associated diseases, and cellular senescence. The work was conducted in various organisms, includingC. elegans, mice, plants, and humans. Topics covered in the symposium stimulated discussion of novel directions for future research on aging. The meeting ended with a commitment for the third International Symposium on the Genetics of Aging and Life History, which will be held in 2016.

  17. Ethylene oxide: induction of specific-locus mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa and implications for genetic risk assessment of human exposure in the workplace.

    PubMed

    de Serres, F J; Brockman, H E

    1995-04-01

    Ethylene oxide (ETO) is an important industrial intermediate used extensively in the production of ethylene glycol, as a fumigant, and as a sterilant of choice for various medical devices. The mutagenicity of ETO was studied for the induction of specific-locus mutations in the adenine-3 (ad-3) region of a two-component heterokaryon (H-12) of Neurospora crassa. The objectives of these studies with ETO were to rank its mutagenic potency and to compare its mutational spectrum for induced specific-locus mutations with other chemical mutagens in this lower eukaryotic organism. Specific-locus mutations in the ad-3 region of heterokaryon H12 result from gene/point mutations at the closely linked ad-3A and ad-3B loci, multilocus deletion mutations and multiple-locus mutations. These major genotypic classes are similar to the types of specific-locus mutations that can be detected in higher organisms. Conidial suspensions of H-12 were treated with five different concentrations of ETO (0.1-0.35%) for 3 h at 25 degrees C. Control and ETO-treated conidial suspensions were used to obtain dose-response curves for inactivation as well as the overall induction of ad-3 forward mutations using a non-selective method based on pigment accumulation rather than a requirement for adenine. The results from these experiments are: (1) the slope of the dose-response curve for ETO-induced specific-locus mutations in the ad-3 region is 1.49 +/- 0.07, and (2) the maximum forward-mutation frequency fell between 10 and 100 ad-3 mutations per 10(6) survivors; therefore, ETO is a moderate mutagen. Classical genetic tests were used to characterize the ETO-induced ad-3 mutations from each of two treatments (0.25 and 0.35%). The overall data base demonstrates that ETO-induced ad-3 mutations result from a high percentage (96.9%) of gene/point mutations at the ad-3A and ad-3B loci, as well as from a low percentage (3.1%) of multilocus deletion mutations. The mutagenic activity of ETO is compared with the

  18. Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21.

    PubMed

    Hamdi, Yosr; Soucy, Penny; Adoue, Véronique; Michailidou, Kyriaki; Canisius, Sander; Lemaçon, Audrey; Droit, Arnaud; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Chang-Claude, Jenny; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G; Goldberg, Mark S; González-Neira, Anna; Grenaker-Alnæs, Grethe; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hallberg, Emily; Hooning, Maartje J; Hopper, John L; Jakubowska, Anna; Jones, Michael; Kabisch, Maria; Kataja, Vesa; Lambrechts, Diether; Le Marchand, Loic; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Maranian, Mel; Margolin, Sara; Marme, Frederik; Milne, Roger L; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Olswold, Curtis; Peto, Julian; Plaseska-Karanfilska, Dijana; Pylkäs, Katri; Radice, Paolo; Rudolph, Anja; Sawyer, Elinor J; Schmidt, Marjanka K; Shu, Xiao-Ou; Southey, Melissa C; Swerdlow, Anthony; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Van Den Ouweland, Ans M W; Wang, Qin; Winqvist, Robert; Zheng, Wei; Benitez, Javier; Chenevix-Trench, Georgia; Dunning, Alison M; Pharoah, Paul D P; Kristensen, Vessela; Hall, Per; Easton, Douglas F; Pastinen, Tomi; Nord, Silje; Simard, Jacques

    2016-12-06

    There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.

  19. 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.

  20. A genome-wide trans-ethnic interaction study links the PIGR-FCAMR locus to coronary atherosclerosis via interactions between genetic variants and residential exposure to traffic

    PubMed Central

    Neas, Lucas M.; Blach, Colette; Haynes, Carol S.; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Z. Elaine; Devlin, Robert B.; Diaz-Sanchez, David; Cascio, Wayne E.; Miranda, Marie Lynn; Gregory, Simon G.; Shah, Svati H.; Kraus, William E.; Hauser, Elizabeth R.

    2017-01-01

    Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic-related air pollution is a widespread environmental exposure and is associated with multiple cardiovascular outcomes such as coronary atherosclerosis, peripheral arterial disease, and myocardial infarction. Despite the recognition of the importance of both genetic and environmental exposures to the pathogenesis of cardiovascular disease, studies of how these two contributors operate jointly are rare. We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis. Using race-stratified cohorts of 538 African-Americans (AA) and 1562 European-Americans (EA) from a cardiac catheterization cohort (CATHGEN), we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes. In the EA GWIS, there were three suggestive interactions; none of these replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation. In conclusion, we have uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution. These genes point towards inflammatory pathways that may modify the effects of air pollution on cardiovascular disease risk. PMID:28355232

  1. Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

    PubMed Central

    Adoue, Véronique; Michailidou, Kyriaki; Canisius, Sander; Lemaçon, Audrey; Droit, Arnaud; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Chang-Claude, Jenny; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dos-Santos-Silva, Isabel; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G.; Goldberg, Mark S.; González-Neira, Anna; Grenaker-Alnæs, Grethe; Guénel, Pascal; Haeberle, Lothar; Haiman, Christopher A.; Hamann, Ute; Hallberg, Emily; Hooning, Maartje J.; Hopper, John L.; Jakubowska, Anna; Jones, Michael; Kabisch, Maria; Kataja, Vesa; Lambrechts, Diether; Marchand, Loic Le; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Maranian, Mel; Margolin, Sara; Marme, Frederik; Milne, Roger L.; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Olswold, Curtis; Peto, Julian; Plaseska-Karanfilska, Dijana; Pylkäs, Katri; Radice, Paolo; Rudolph, Anja; Sawyer, Elinor J.; Schmidt, Marjanka K.; Shu, Xiao-Ou; Southey, Melissa C.; Swerdlow, Anthony; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Van Den Ouweland, Ans M. W.; Wang, Qin; Winqvist, Robert; Investigators, kConFab/AOCS; Zheng, Wei; Benitez, Javier; Chenevix-Trench, Georgia; Dunning, Alison M.; Pharoah, Paul D. P.; Kristensen, Vessela; Hall, Per; Easton, Douglas F.; Pastinen, Tomi; Nord, Silje; Simard, Jacques

    2016-01-01

    There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas. PMID:27792995

  2. Genetic variants and cellular stressors associated with exfoliation syndrome modulate promoter activity of a lncRNA within the LOXL1 locus

    PubMed Central

    Hauser, Michael A.; Aboobakar, Inas F.; Liu, Yutao; Miura, Shiroh; Whigham, Benjamin T.; Challa, Pratap; Wheeler, Joshua; Williams, Andrew; Santiago-Turla, Cecelia; Qin, Xuejun; Rautenbach, Robyn M.; Ziskind, Ari; Ramsay, Michèle; Uebe, Steffen; Song, Lingyun; Safi, Alexias; Vithana, Eranga N.; Mizoguchi, Takanori; Nakano, Satoko; Kubota, Toshiaki; Hayashi, Ken; Manabe, Shin-ichi; Kazama, Shigeyasu; Mori, Yosai; Miyata, Kazunori; Yoshimura, Nagahisa; Reis, Andre; Crawford, Gregory E.; Pasutto, Francesca; Carmichael, Trevor R.; Williams, Susan E. I.; Ozaki, Mineo; Aung, Tin; Khor, Chiea-Chuen; Stamer, W. Daniel; Ashley-Koch, Allison E.; Allingham, R. Rand

    2015-01-01

    Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (∼40 kb) in 50 indigenous, black South African XFS cases and 50 matched controls. The variants with the strongest evidence of association were located in a well-defined 7-kb region bounded by the 3'-end of exon 1 and the adjacent region of intron 1 of LOXL1. We replicated this finding in US Caucasian (91 cases/1031 controls), German (771 cases/1365 controls) and Japanese (1484 cases/1188 controls) populations. The region of peak association lies upstream of LOXL1-AS1, a long non-coding RNA (lncRNA) encoded on the opposite strand of LOXL1. We show that this region contains a promoter and, importantly, that the strongly associated XFS risk alleles in the South African population are functional variants that significantly modulate the activity of this promoter. LOXL1-AS1 expression is also significantly altered in response to oxidative stress in human lens epithelial cells and in response to cyclic mechanical stress in human Schlemm's canal endothelial cells. Taken together, these findings support a functional role for the LOXL1-AS1 lncRNA in cellular stress response and suggest that dysregulation of its expression by genetic risk variants plays a key role in XFS pathogenesis. PMID:26307087

  3. The grain Hardness locus characterized in a diverse wheat panel (Triticum aestivum L.) adapted to the central part of the Fertile Crescent: genetic diversity, haplotype structure, and phylogeny.

    PubMed

    Shaaf, Salar; Sharma, Rajiv; Baloch, Faheem Shehzad; Badaeva, Ekaterina D; Knüpffer, Helmut; Kilian, Benjamin; Özkan, Hakan

    2016-06-01

    Wheat belongs to the most important crops domesticated in the Fertile Crescent. In this region, fortunately, locally adapted wheat landraces are still present in farmers' fields. This material might be of immense value for future breeding programs. However, especially wheat germplasm adapted to the central part of the Fertile Crescent has been poorly characterized for allelic variation at key loci of agricultural importance. Grain hardness is an important trait influencing milling and baking quality of wheat. This trait is mainly determined by three tightly linked genes, namely, Puroindoline a (Pina), Puroindoline b (Pinb), and Grain softness protein-1 (Gsp-1), at the Hardness (Ha-D) locus on chromosome 5DS. To investigate genetic diversity and haplotype structure, we resequenced 96 diverse wheat lines at Pina-D1, Pinb-D1, Gsp-A1, Gsp-B1, and Gsp-D1. Three types of null alleles were identified using diagnostic primers: the first type was a multiple deletion of Pina-D1, Pinb-D1, and Gsp-D1 (Pina-D1k), the second was a Pina-D1 deletion (Pina-D1b); and the third type was a deletion of Gsp-D1, representing a novel null allele designated here as Gsp-D1k. Sequence analysis resulted in four allelic variants at Pinb-D1 and five at Gsp-A1, among them Gsp-A1-V was novel. Pina-D1, Gsp-B1 and Gsp-D1 sequences were monomorphic. Haplotype and phylogenetic analysis suggested that (1) bread wheat inherited its 5DS telomeric region probably from wild diploid Ae. tauschii subsp. tauschii found within an area from Transcaucasia to Caspian Iran; and that (2) the Ha-A and Ha-B homoeoloci were most closely related to sequences of wild tetraploid T. dicocco ides. This study provides a good overview of available genetic diversity at Pina-D1, Pinb-D1, and Gsp-1, which can be exploited to extend the range of grain texture traits in wheat.

  4. Host Genetic Control of the Microbiome in Humans and Maise or Relating Host Genetic Variation to the Microbiome (2011 JGI User Meeting)

    SciTech Connect

    Ley, Ruth

    2011-03-23

    The U.S. Department of Energy Joint Genome Institute (JGI) invited scientists interested in the application of genomics to bioenergy and environmental issues, as well as all current and prospective users and collaborators, to attend the annual DOE JGI Genomics of Energy & Environment Meeting held March 22-24, 2011 in Walnut Creek, Calif. The emphasis of this meeting was on the genomics of renewable energy strategies, carbon cycling, environmental gene discovery, and engineering of fuel-producing organisms. The meeting features presentations by leading scientists advancing these topics. Ruth Ley of Cornell University gives a presentation on "Relating Host Genetic Variation to the Microbiome" at the 6th annual Genomics of Energy & Environment Meeting on March 23, 2011.

  5. Host Genetic Control of the Microbiome in Humans and Maise or Relating Host Genetic Variation to the Microbiome (2011 JGI User Meeting)

    ScienceCinema

    Ley, Ruth [Cornell University

    2016-07-12

    The U.S. Department of Energy Joint Genome Institute (JGI) invited scientists interested in the application of genomics to bioenergy and environmental issues, as well as all current and prospective users and collaborators, to attend the annual DOE JGI Genomics of Energy & Environment Meeting held March 22-24, 2011 in Walnut Creek, Calif. The emphasis of this meeting was on the genomics of renewable energy strategies, carbon cycling, environmental gene discovery, and engineering of fuel-producing organisms. The meeting features presentations by leading scientists advancing these topics. Ruth Ley of Cornell University gives a presentation on "Relating Host Genetic Variation to the Microbiome" at the 6th annual Genomics of Energy & Environment Meeting on March 23, 2011.

  6. Spatial Variation in Genetic Diversity and Natural Selection on the Thrombospondin-Related Adhesive Protein Locus of Plasmodium vivax (PvTRAP)

    PubMed Central

    Kosuwin, Rattiporn; Putaporntip, Chaturong; Tachibana, Hiroshi; Jongwutiwes, Somchai

    2014-01-01

    Thrombospondin-related adhesive protein (TRAP) of malaria parasites is essential for sporozoite motility and invasions into mosquito’s salivary gland and vertebrate’s hepatocyte; thereby, it is a promising target for pre-erythrocytic vaccine. TRAP of Plasmodium vivax (PvTRAP) exhibits sequence heterogeneity among isolates, an issue relevant to vaccine development. To gain insights into variation in the complete PvTRAP sequences of parasites in Thailand, 114 vivax malaria patients were recruited in 2006–2007 from 4 major endemic provinces bordering Myanmar (Tak in the northwest, n = 30 and Prachuap Khirikhan in the southwest, n = 25), Cambodia (Chanthaburi in the east, n = 29) and Malaysia (Yala and Narathiwat in the south, n = 30). In total, 26 amino acid substitutions were detected and 9 of which were novel, resulting in 44 distinct haplotypes. Haplotype and nucleotide diversities were lowest in southern P. vivax population while higher levels of diversities were observed in other populations. Evidences of positive selection on PvTRAP were demonstrated in domains II and IV and purifying selection in domains I, II and VI. Genetic differentiation was significant between each population except that between populations bordering Myanmar where transmigration was common. Regression analysis of pairwise linearized Fst and geographic distance suggests that P. vivax populations in Thailand have been isolated by distance. Sequence diversity of PvTRAP seems to be temporally stable over one decade in Tak province based on comparison of isolates collected in 1996 (n = 36) and 2006–2007. Besides natural selection, evidences of intragenic recombination have been supported in this study that could maintain and further generate diversity in this locus. It remains to be investigated whether amino acid substitutions in PvTRAP could influence host immune responses although several predicted variant T cell epitopes drastically altered the epitope scores

  7. Spatial variation in genetic diversity and natural selection on the thrombospondin-related adhesive protein locus of Plasmodium vivax (PvTRAP).

    PubMed

    Kosuwin, Rattiporn; Putaporntip, Chaturong; Tachibana, Hiroshi; Jongwutiwes, Somchai

    2014-01-01

    Thrombospondin-related adhesive protein (TRAP) of malaria parasites is essential for sporozoite motility and invasions into mosquito's salivary gland and vertebrate's hepatocyte; thereby, it is a promising target for pre-erythrocytic vaccine. TRAP of Plasmodium vivax (PvTRAP) exhibits sequence heterogeneity among isolates, an issue relevant to vaccine development. To gain insights into variation in the complete PvTRAP sequences of parasites in Thailand, 114 vivax malaria patients were recruited in 2006-2007 from 4 major endemic provinces bordering Myanmar (Tak in the northwest, n = 30 and Prachuap Khirikhan in the southwest, n = 25), Cambodia (Chanthaburi in the east, n = 29) and Malaysia (Yala and Narathiwat in the south, n = 30). In total, 26 amino acid substitutions were detected and 9 of which were novel, resulting in 44 distinct haplotypes. Haplotype and nucleotide diversities were lowest in southern P. vivax population while higher levels of diversities were observed in other populations. Evidences of positive selection on PvTRAP were demonstrated in domains II and IV and purifying selection in domains I, II and VI. Genetic differentiation was significant between each population except that between populations bordering Myanmar where transmigration was common. Regression analysis of pairwise linearized Fst and geographic distance suggests that P. vivax populations in Thailand have been isolated by distance. Sequence diversity of PvTRAP seems to be temporally stable over one decade in Tak province based on comparison of isolates collected in 1996 (n = 36) and 2006-2007. Besides natural selection, evidences of intragenic recombination have been supported in this study that could maintain and further generate diversity in this locus. It remains to be investigated whether amino acid substitutions in PvTRAP could influence host immune responses although several predicted variant T cell epitopes drastically altered the epitope scores. Knowledge

  8. The third international meeting on genetic disorders in the RAS/MAPK pathway: towards a therapeutic approach.

    PubMed

    Korf, Bruce; Ahmadian, Reza; Allanson, Judith; Aoki, Yoko; Bakker, Annette; Wright, Emma Burkitt; Denger, Brian; Elgersma, Ype; Gelb, Bruce D; Gripp, Karen W; Kerr, Bronwyn; Kontaridis, Maria; Lazaro, Conxi; Linardic, Corinne; Lozano, Reymundo; MacRae, Calum A; Messiaen, Ludwine; Mulero-Navarro, Sonia; Neel, Benjamin; Plotkin, Scott; Rauen, Katherine A; Roberts, Amy; Silva, Alcino J; Sittampalam, Sitta G; Zhang, Chao; Schoyer, Lisa

    2015-08-01

    "The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach" was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion.

  9. The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Toward a Therapeutic Approach

    PubMed Central

    Korf, Bruce; Ahmadian, Reza; Allanson, Judith; Aoki, Yoko; Bakker, Annette; Wright, Emma Burkitt; Denger, Brian; Elgersma, Ype; Gelb, Bruce D.; Gripp, Karen W.; Kerr, Bronwyn; Kontaridis, Maria; Lazaro, Conxi; Linardic, Corinne; Lozano, Reymundo; MacRae, Calum A.; Messiaen, Ludwine; Mulero-Navarro, Sonia; Neel, Benjamin; Plotkin, Scott; Rauen, Katherine A.; Roberts, Amy; Silva, Alcino J.; Sittampalam, Sitta G.; Zhang, Chao; Schoyer, Lisa

    2015-01-01

    “The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach” was held at the Renaissance Orlando at SeaWorld Hotel (August 2–4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion. PMID:25900621

  10. Genetic characterization of the hmp locus, a chemotaxis-like gene cluster that regulates hormogonium development and motility in Nostoc punctiforme.

    PubMed

    Risser, Douglas D; Chew, William G; Meeks, John C

    2014-04-01

    Filamentous cyanobacteria are capable of gliding motility, but the mechanism of motility is not well defined. Here we present a detailed characterization of the hmp locus from Nostoc punctiforme, which encodes chemotaxis-like proteins. Deletions of hmpB, C, D and E abolished differentiation of hormogonia under standard growth conditions, but, upon addition of a symbiotic partner exudate, the mutant strains differentiated hormogonium-like filaments that lacked motility and failed to secrete hormogonium specific polysaccharide. The hmp locus is expressed as two transcripts, one originating 5' of hmpA and encompassing the entire hmp locus, and the other 5' of hmpB and encompassing hmpBCDE. The CheA-like HmpE donates phosphate to its own C-terminal receiver domain, and to the CheY-like HmpB, but not to the PatA family CheY-like HmpA. A GFP-tagged variant of each hmp locus protein localized to a ring adjacent to the septum on each end of the rod-shaped cell. Immunofluorescence demonstrated that PilA localizes to a ring at the junction between cells. The phenotype of the deletion strains, and the localization of the Hmp proteins and the putative PilA protein to rings at the cell junctions are consistent with the hypothesis that these proteins are part of the junctional pore complex observed in a number of filamentous cyanobacteria.

  11. Molecular Identification of the Schwannomatosis Locus

    DTIC Science & Technology

    2005-07-01

    AD Award Number: DAMD17-03-1-0445 TITLE: Molecular Identification of the Schwannomatosis Locus PRINCIPAL INVESTIGATOR: Mia M. MacCollin, M.D...NUMBER Molecular Identification of the Schwannomatosis Locus 5b. GRANT NUMBER DAMD17-03-1-0445 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...can be found on next page. 15. SUBJECT TERMS schwannomatosis, tumor suppressor gene, NF2, molecular genetics 16. SECURITY CLASSIFICATION OF: 17

  12. Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report

    SciTech Connect

    Duster, T.

    1998-11-01

    The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

  13. Genetic Variation at Exon 2 of the MHC Class II DQB Locus in Blue Whale (Balaenoptera musculus) from the Gulf of California.

    PubMed

    Moreno-Santillán, Diana D; Lacey, Eileen A; Gendron, Diane; Ortega, Jorge

    2016-01-01

    The genes of the Major Histocompatibility Complex (MHC) play an important role in the vertebrate immune response and are among the most polymorphic genes known in vertebrates. In some marine mammals, MHC genes have been shown to be characterized by low levels of polymorphism compared to terrestrial taxa; this reduction in variation is often explained as a result of lower pathogen pressures in marine habitats. To determine if this same reduction in variation applies to the migratory population of blue whales (Balaenoptera musculus) that occurs in the Gulf of California, we genotyped a 172 bp fragment of exon 2 of the MHC Class II DQB locus for 80 members of this population. Twenty-two putatively functional DQB allotypes were identified, all of which were homologous with DQB sequences from other cetacean species. Up to 5 putative alleles per individual were identified, suggesting that gene duplication has occurred at this locus. Rates of non-synonymous to synonymous substitutions (ω) and maximum likelihood analyses of models of nucleotide variation provided potential evidence of ongoing positive selection at this exon. Phylogenetic analyses of DQB alleles from B. musculus and 16 other species of cetaceans revealed trans-specific conservation of MHC variants, suggesting that selection has acted on this locus over prolonged periods of time. Collectively our findings reveal that immunogenic variation in blue whales is comparable to that in terrestrial mammals, thereby providing no evidence that marine taxa are subject to reduced pathogen-induced selective pressures.

  14. Genetic Variation at Exon 2 of the MHC Class II DQB Locus in Blue Whale (Balaenoptera musculus) from the Gulf of California

    PubMed Central

    Moreno-Santillán, Diana D.; Lacey, Eileen A.; Gendron, Diane; Ortega, Jorge

    2016-01-01

    The genes of the Major Histocompatibility Complex (MHC) play an important role in the vertebrate immune response and are among the most polymorphic genes known in vertebrates. In some marine mammals, MHC genes have been shown to be characterized by low levels of polymorphism compared to terrestrial taxa; this reduction in variation is often explained as a result of lower pathogen pressures in marine habitats. To determine if this same reduction in variation applies to the migratory population of blue whales (Balaenoptera musculus) that occurs in the Gulf of California, we genotyped a 172 bp fragment of exon 2 of the MHC Class II DQB locus for 80 members of this population. Twenty-two putatively functional DQB allotypes were identified, all of which were homologous with DQB sequences from other cetacean species. Up to 5 putative alleles per individual were identified, suggesting that gene duplication has occurred at this locus. Rates of non-synonymous to synonymous substitutions (ω) and maximum likelihood analyses of models of nucleotide variation provided potential evidence of ongoing positive selection at this exon. Phylogenetic analyses of DQB alleles from B. musculus and 16 other species of cetaceans revealed trans-specific conservation of MHC variants, suggesting that selection has acted on this locus over prolonged periods of time. Collectively our findings reveal that immunogenic variation in blue whales is comparable to that in terrestrial mammals, thereby providing no evidence that marine taxa are subject to reduced pathogen-induced selective pressures. PMID:26761201

  15. Genetic Regulation of Grass Biomass Accumulation and Biological Conversion Quality (2013 DOE JGI Genomics of Energy and Environment 8th Annual User Meeting)

    SciTech Connect

    Hazen, Sam

    2013-03-01

    Sam Hazen of the University of Massachusetts on "Genetic Regulation of Grass Biomass Accumulation and Biological Conversion Quality" at the 8th Annual Genomics of Energy & Environment Meeting on March 27, 2013 in Walnut Creek, Calif.

  16. Molecular Typing of Mycobacterium Tuberculosis Complex by 24-Locus Based MIRU-VNTR Typing in Conjunction with Spoligotyping to Assess Genetic Diversity of Strains Circulating in Morocco

    PubMed Central

    Bouklata, Nada; Supply, Philip; Jaouhari, Sanae; Charof, Reda; Seghrouchni, Fouad; Sadki, Khalid; El Achhab, Youness; Nejjari, Chakib; Filali-Maltouf, Abdelkarim

    2015-01-01

    Background Standard 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-VNTR) typing allows to get an improved resolution power for tracing TB transmission and predicting different strain (sub) lineages in a community. Methodology During 2010–2012, a total of 168 Mycobacterium tuberculosis Complex (MTBC) isolates were collected by cluster sampling from 10 different Moroccan cities, and centralized by the National Reference Laboratory of Tuberculosis over the study period. All isolates were genotyped using spoligotyping, and a subset of 75 was genotyped using 24-locus based MIRU-VNTR typing, followed by first line drug susceptibility testing. Corresponding strain lineages were predicted using MIRU-VNTRplus database. Principal Findings Spoligotyping resulted in 137 isolates in 18 clusters (2–50 isolates per cluster: clustering rate of 81.54%) corresponding to a SIT number in the SITVIT database, while 31(18.45%) patterns were unique of which 10 were labelled as “unknown” according to the same database. The most prevalent spoligotype family was LAM; (n = 81 or 48.24% of isolates, dominated by SIT42, n = 49), followed by Haarlem (23.80%), T superfamily (15.47%), >Beijing (2.97%), > U clade (2.38%) and S clade (1.19%). Subsequent 24-Locus MIRU-VNTR typing identified 64 unique types and 11 isolates in 5 clusters (2 to 3isolates per cluster), substantially reducing clusters defined by spoligotyping only. The single cluster of three isolates corresponded to two previously treated MDR-TB cases and one new MDR-TB case known to be contact a same index case and belonging to a same family, albeit residing in 3 different administrative regions. MIRU-VNTR loci 4052, 802, 2996, 2163b, 3690, 1955, 424, 2531, 2401 and 960 were highly discriminative in our setting (HGDI >0.6). Conclusions 24-locus MIRU-VNTR typing can substantially improve the resolution of large clusters initially defined by spoligotyping alone and predominating in Morocco

  17. Genetic recombination at the human RH locus: A family study of the red-cell Evans phenotype reveals a transfer of exons 2-6 from the RHD to the RHCE gene

    SciTech Connect

    Huang, C.H.; Chen, Y.; Reid, M.; Ghosh, S.

    1996-10-01

    The human RH locus appears to consist of two structural genes, D and CE, which map on the short arm p34-36 of chromosome 1 and specify a most complex system of blood-group genetic polymorphisms. Here we describe a family study of the Evans (also known as {open_quotes}D..{open_quotes}) phenotype, a codominant trait associated with both qualitative and quantitative changes in D-antigen expression. A cataract-causing mutation was also inherited in this family and was apparently cotransmitted with Evans, suggesting a chromosomal linkage of these two otherwise unrelated traits. Southern blot analysis and allele-specific PCR showed the linkage of Evans with a SphI RFLP marker and the presence of a hybrid gene in the RH locus. To delineate the pattern of gene expression, the composition and structure of Rh-polypeptide transcripts were characterized by reverse transcriptase-PCR and nucleotide sequencing. This resulted in the identification of a novel Rh transcript expressed only in the Evans-positive erythroid cells. Sequence analysis showed that the transcript maintained a normal open reading frame but occurred as a CE-D-CE composite in which exons 2-6 of the CE gene were replaced by the homologous counterpart of the D gene. This hybrid gene was predicted to encode a CE-D-CE fusion protein whose surface expression correlates with the Evans phenotype. The mode and consequence of such a recombination event suggest the occurrence, in the RH locus, of a segmental DNA transfer via the mechanism of gene conversion. 31 refs., 6 figs., 1 tab.

  18. Genetic dissection of a TIR-NB-LRR locus from the wild North American grapevine species Muscadinia rotundifolia identifies paralogous genes conferring resistance to major fungal and oomycete pathogens in cultivated grapevine.

    PubMed

    Feechan, Angela; Anderson, Claire; Torregrosa, Laurent; Jermakow, Angelica; Mestre, Pere; Wiedemann-Merdinoglu, Sabine; Merdinoglu, Didier; Walker, Amanda R; Cadle-Davidson, Lance; Reisch, Bruce; Aubourg, Sebastien; Bentahar, Nadia; Shrestha, Bipna; Bouquet, Alain; Adam-Blondon, Anne-Françoise; Thomas, Mark R; Dry, Ian B

    2013-11-01

    The most economically important diseases of grapevine cultivation worldwide are caused by the fungal pathogen powdery mildew (Erysiphe necator syn. Uncinula necator) and the oomycete pathogen downy mildew (Plasmopara viticola). Currently, grapegrowers rely heavily on the use of agrochemicals to minimize the potentially devastating impact of these pathogens on grape yield and quality. The wild North American grapevine species Muscadinia rotundifolia was recognized as early as 1889 to be resistant to both powdery and downy mildew. We have now mapped resistance to these two mildew pathogens in M. rotundifolia to a single locus on chromosome 12 that contains a family of seven TIR-NB-LRR genes. We further demonstrate that two highly homologous (86% amino acid identity) members of this gene family confer strong resistance to these unrelated pathogens following genetic transformation into susceptible Vitis vinifera winegrape cultivars. These two genes, designated resistance to Uncinula necator (MrRUN1) and resistance to Plasmopara viticola (MrRPV1) are the first resistance genes to be cloned from a grapevine species. Both MrRUN1 and MrRPV1 were found to confer resistance to multiple powdery and downy mildew isolates from France, North America and Australia; however, a single powdery mildew isolate collected from the south-eastern region of North America, to which M. rotundifolia is native, was capable of breaking MrRUN1-mediated resistance. Comparisons of gene organization and coding sequences between M. rotundifolia and the cultivated grapevine V. vinifera at the MrRUN1/MrRPV1 locus revealed a high level of synteny, suggesting that the TIR-NB-LRR genes at this locus share a common ancestor.

  19. Meeting review. Uncovering the genetic basis of adaptive change: on the intersection of landscape genomics and theoretical population genetics.

    PubMed

    Joost, Stéphane; Vuilleumier, Séverine; Jensen, Jeffrey D; Schoville, Sean; Leempoel, Kevin; Stucki, Sylvie; Widmer, Ivo; Melodelima, Christelle; Rolland, Jonathan; Manel, Stéphanie

    2013-07-01

    A workshop recently held at the École Polytechnique Fédérale de Lausanne (EPFL, Switzerland) was dedicated to understanding the genetic basis of adaptive change, taking stock of the different approaches developed in theoretical population genetics and landscape genomics and bringing together knowledge accumulated in both research fields. Indeed, an important challenge in theoretical population genetics is to incorporate effects of demographic history and population structure. But important design problems (e.g. focus on populations as units, focus on hard selective sweeps, no hypothesis-based framework in the design of the statistical tests) reduce their capability of detecting adaptive genetic variation. In parallel, landscape genomics offers a solution to several of these problems and provides a number of advantages (e.g. fast computation, landscape heterogeneity integration). But the approach makes several implicit assumptions that should be carefully considered (e.g. selection has had enough time to create a functional relationship between the allele distribution and the environmental variable, or this functional relationship is assumed to be constant). To address the respective strengths and weaknesses mentioned above, the workshop brought together a panel of experts from both disciplines to present their work and discuss the relevance of combining these approaches, possibly resulting in a joint software solution in the future.

  20. A census of cells in time: quantitative genetics meets developmental biology.

    PubMed

    Chitwood, Daniel H; Sinha, Neelima R

    2013-02-01

    Quantitative genetics has become a popular method for determining the genetic basis of natural variation. Combined with genomic methods, it provides a tool for discerning the genetic basis of gene expression. So-called genetical genomics approaches yield a wealth of genomic information, but by necessity, because of cost and time, fail to resolve the differences between organs, tissues, and/or cell types. Similarly, quantitative approaches in development that might potentially address these issues are seldom applied to quantitative genetics. We discuss recent advances in cell type-specific isolation methods, the quantitative analysis of phenotype, and developmental modeling that are compatible with quantitative genetics and, with time, promise to bridge the gap between these two powerful disciplines yielding unprecedented biological insight.

  1. Which Sry locus is the hypertensive Y chromosome locus?

    PubMed

    Turner, Monte E; Farkas, Joel; Dunmire, Jeff; Ely, Daniel; Milsted, Amy

    2009-02-01

    The Y chromosome of the spontaneously hypertensive rat (SHR) contains a genetic component that raises blood pressure compared with the Wistar-Kyoto (WKY) Y chromosome. This research tests the Sry gene complex as the hypertensive component of the SHR Y chromosome. The Sry loci were sequenced in 1 strain with a hypertensive Y chromosome (SHR/Akr) and 2 strains with a normotensive Y chromosome (SHR/Crl and WKY/Akr). Both SHR strains have 7 Sry loci, whereas the WKY strain has 6. The 6 loci in common between SHR and WKY strains were identical in the sequence compared (coding region, 392-bp 5' prime flanking, 1200-bp 3' flanking). Both SHR strains have a locus (Sry3) not found in WKY rats, but this locus is different between SHR/Akr and SHR/Crl rats. Six mutations have accumulated in Sry3 between the SHR strains, whereas the other 6 Sry loci are identical. This pattern of an SHR-specific locus and mutation in this locus in SHR/Crl coinciding with the loss of Y chromosome hypertension is an expected pattern if Sry3 is the Y chromosome-hypertensive component. The SHR/y strain showed a significant increase in total Sry expression in the kidney between 4 and 15 weeks of age. There are significant differences in Sry expression between adrenal glands and the kidney (15 to 30 times higher in kidneys) but no significant differences between strains. These results, along with previous studies demonstrating an interaction of Sry with the tyrosine hydroxylase promoter and increased blood pressure with exogenous Sry expression, suggest the Sry loci as the hypertensive component of the SHR Y chromosome.

  2. Popliteal pterygium syndrome in a Swedish family--clinical findings and genetic analysis with the van der Woude syndrome locus at 1q32-q41.

    PubMed

    Wong, F K; Gustafsson, B

    2000-04-01

    The present study describes a Swedish family in which the mother and her son were affected with signs of popliteal pterygium syndrome (PPS, OMIM 119500). Both individuals had bilateral complete cleft lip and palate, oral synechiae, paramedian pits on the lower lip, toe syndactyly and a piece of triangular skin overgrowth on the great toes. The son also presented with soft tissue syndactyly of the 2nd and 3rd fingers. Although popliteal pterygium was not found, the above clinical features were diagnostic for PPS. Chromosomal abnormalities were not revealed in either case by cytogenetic analyses. A test for microdeletion in the VWS region at 1q32-q41 was performed in the family using 5 polymorphic microsatellite markers from the region. The affected son was found to be heterozygous for all 5 markers, suggesting that microdeletion at the VWS region was unlikely. The VWS locus, however, was not excluded by haplotype analysis of the family.

  3. Chimerization at the AQP2-AQP3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates.

    PubMed

    Graf, Fabrice E; Baker, Nicola; Munday, Jane C; de Koning, Harry P; Horn, David; Mäser, Pascal

    2015-08-01

    Aquaglyceroporin-2 is a known determinant of melarsoprol-pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2-AQP3 tandem locus was described from melarsoprol-pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2-aqp3 null T. b. brucei does not. This proves that AQP2-AQP3 chimerization is the cause of melarsoprol-pentamidine cross-resistance in the T. b. gambiense isolates.

  4. Genetic control of a central pattern generator: rhythmic oromotor movement in mice is controlled by a major locus near Atp1a2.

    PubMed

    Boughter, John D; Mulligan, Megan K; St John, Steven J; Tokita, Kenichi; Lu, Lu; Heck, Detlef H; Williams, Robert W

    2012-01-01

    Fluid licking in mice is a rhythmic behavior that is controlled by a central pattern generator (CPG) located in a complex of brainstem nuclei. C57BL/6J (B6) and DBA/2J (D2) strains differ significantly in water-restricted licking, with a highly heritable difference in rates (h(2)≥0.62) and a corresponding 20% difference in interlick interval (mean ± SEM = 116.3±1 vs 95.4±1.1 ms). We systematically quantified motor output in these strains, their F(1) hybrids, and a set of 64 BXD progeny strains. The mean primary interlick interval (MPI) varied continuously among progeny strains. We detected a significant quantitative trait locus (QTL) for a CPG controlling lick rate on Chr 1 (Lick1), and a suggestive locus on Chr 10 (Lick10). Linkage was verified by testing of B6.D2-1D congenic stock in which a segment of Chr 1 of the D2 strain was introgressed onto the B6 parent. The Lick1 interval on distal Chr 1 contains several strong candidate genes. One of these is a sodium/potassium pump subunit (Atp1a2) with widespread expression in astrocytes, as well as in a restricted population of neurons. Both this subunit and the entire Na(+)/K(+)-ATPase molecule have been implicated in rhythmogenesis for respiration and locomotion. Sequence variants in or near Apt1a2 strongly modulate expression of the cognate mRNA in multiple brain regions. This gene region has recently been sequenced exhaustively and we have cataloged over 300 non-coding and synonymous mutations segregating among BXD strains, one or more of which is likely to contribute to differences in central pattern generator tempo.

  5. Genetic Control of a Central Pattern Generator: Rhythmic Oromotor Movement in Mice Is Controlled by a Major Locus near Atp1a2

    PubMed Central

    Boughter, John D.; Mulligan, Megan K.; St. John, Steven J.; Tokita, Kenichi; Lu, Lu; Heck, Detlef H.; Williams, Robert W.

    2012-01-01

    Fluid licking in mice is a rhythmic behavior that is controlled by a central pattern generator (CPG) located in a complex of brainstem nuclei. C57BL/6J (B6) and DBA/2J (D2) strains differ significantly in water-restricted licking, with a highly heritable difference in rates (h2≥0.62) and a corresponding 20% difference in interlick interval (mean ± SEM = 116.3±1 vs 95.4±1.1 ms). We systematically quantified motor output in these strains, their F1 hybrids, and a set of 64 BXD progeny strains. The mean primary interlick interval (MPI) varied continuously among progeny strains. We detected a significant quantitative trait locus (QTL) for a CPG controlling lick rate on Chr 1 (Lick1), and a suggestive locus on Chr 10 (Lick10). Linkage was verified by testing of B6.D2-1D congenic stock in which a segment of Chr 1 of the D2 strain was introgressed onto the B6 parent. The Lick1 interval on distal Chr 1 contains several strong candidate genes. One of these is a sodium/potassium pump subunit (Atp1a2) with widespread expression in astrocytes, as well as in a restricted population of neurons. Both this subunit and the entire Na+/K+-ATPase molecule have been implicated in rhythmogenesis for respiration and locomotion. Sequence variants in or near Apt1a2 strongly modulate expression of the cognate mRNA in multiple brain regions. This gene region has recently been sequenced exhaustively and we have cataloged over 300 non-coding and synonymous mutations segregating among BXD strains, one or more of which is likely to contribute to differences in central pattern generator tempo. PMID:22675444

  6. 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.

  7. 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.

  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. Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction

    PubMed Central

    Pu, Xiangyuan; Ren, Meixia; An, Weiwei; Zhang, Ruoxin; Yan, Shunying; Situ, Haiteng; He, Xinjie; Chen, Yequn; Tan, Xuerui; Xiao, Qingzhong; Tucker, Arthur T.; Caulfield, Mark J.; Ye, Shu

    2016-01-01

    Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD

  10. Genetic interactions between diverged alleles of Early heading date 1 (Ehd1) and Heading date 3a (Hd3a)/ RICE FLOWERING LOCUS T1 (RFT1) control differential heading and contribute to regional adaptation in rice (Oryza sativa).

    PubMed

    Zhao, Jing; Chen, Hongyi; Ren, Ding; Tang, Huiwu; Qiu, Rong; Feng, Jinglei; Long, Yunming; Niu, Baixiao; Chen, Danping; Zhong, Tianyu; Liu, Yao-Guang; Guo, Jingxin

    2015-11-01

    Initiation of flowering, also called heading, in rice (Oryza sativa) is determined by the florigens encoded by Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 (RFT1). Early heading date 1 (Ehd1) regulates Hd3a and RFT1. However, different rice varieties have diverged alleles of Ehd1 and Hd3a/RFT1 and their genetic interactions remain largely unclear. Here we generated three segregating populations for different combinations of diverged Ehd1 and Hd3a/RFT1 alleles, and analyzed their genetic interactions between these alleles. We demonstrated that, in an ehd1 mutant background, Hd3a was silenced, but RFT1 was expressed (although at lower levels than in plants with a functional Ehd1) under short-day (SD) and long-day (LD) conditions. We identified a nonfunctional RFT1 allele (rft1); the lines carrying homozygous ehd1 and Hd3a/rft1 failed to induce the floral transition under SD and LD conditions. Like Hd3a, RFT1 also interacted with 14-3-3 proteins, the florigen receptors, but a nonfunctional RFT1 with a crucial E105K mutation failed to interact with 14-3-3 proteins. Furthermore, analyses of sequence variation and geographic distribution suggested that functional RFT1 alleles were selected during rice adaptation to high-latitude regions. Our results demonstrate the important roles of RFT1 in rice flowering and regional adaptation.

  11. Natural Product Chemistry Meets Genetics: When is a Genotype a Chemotype?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chemotype of a microbial or plant species has traditionally been defined as its profile of natural products, and the genotype as its genetic constitution or DNA sequence. The purpose of this perspective is to discuss applications of DNA genotyping, particularly by PCR-amplification methods, to ...

  12. Mendel Meets CSI: Forensic Genotyping as a Method to Teach Genetics & DNA Science

    ERIC Educational Resources Information Center

    Kurowski, Scotia; Reiss, Rebecca

    2007-01-01

    This article describes a forensic DNA science laboratory exercise for advanced high school and introductory college level biology courses. Students use a commercial genotyping kit and genetic analyzer or gene sequencer to analyze DNA recovered from a fictitious crime scene. DNA profiling and STR genotyping are outlined. DNA extraction, PCR, and…

  13. Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our goal was to determine whether genetic variation at genes affecting statin metabolism or targets of statin therapy would influence low density lipoprotein (LDL) cholesterol lowering with pravastatin, baseline heart disease, or cardiac endpoints on trial. We examined associations of single nucleot...

  14. Molecular analysis of the bacteriocin-encoding plasmid pDGL1 from Enterococcus durans and genetic characterization of the durancin locus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enterococci constitute a significant component of lactic acid bacteria normally present in the intestinal microflora and include strains that produce bacteriocins. The genetic determinants for durancin GL in Enterococcus durans 41D were identified on the 8,347 bp plasmid pDGL1 by plasmid curing exp...

  15. Genotype-by-sequencing facilitates genetic mapping of a stem rust resistance locus in Aegilops umbellulata, a wild relative of cultivated wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Wild relatives of wheat play a significant role in wheat improvement as a source of genetic diversity. Stem rust disease of wheat causes significant yield losses at the global level and stem rust pathogen race TTKSK (Ug99) is virulent to most previously deployed resistance genes. Therefo...

  16. GENETIC VARIATION AT AN IMMUNE SYSTEM LOCUS PROVIDES BOTH A GENERALIZED AND SPECIFIC STRESS INDICATOR: EFFECTS OF PERSISTENT, BIOACCUMULATIVE AND TOXIC CONTAIMINANT EXPOSURES ON AN ESTUARINE FISH POPULATION

    EPA Science Inventory

    The major histocompatibility complex (MHC) is a group of linked genes that mediates the adaptive immune response in vertebrates. Studies using mammals and birds have shown that environmental stressors can directly and indirectly produce genetic changes at MHC loci that can affect...

  17. STRONG SELECTIVE SIGNAL AND HIGH GENETIC VARIABILITY AT AN IMMUNE SYSTEM LOCUS IN CONTAMINATED AND UNCONTAMINATED POPULATIONS OF AN ESTUARINE FISH

    EPA Science Inventory

    The major histocompatibility complex (MHC) is a group of linked genes that mediates the adaptive immune response in vertebrates. Studies using mammals and birds have shown that environmental stressors can produce genetic changes at MHC loci that can affect immune system function....

  18. 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.

  19. Novel genetic locus implicated for HIV-1 acquisition with putative regulatory links to HIV replication and infectivity: a genome-wide association study.

    PubMed

    Johnson, Eric O; Hancock, Dana B; Gaddis, Nathan C; Levy, Joshua L; Page, Grier; Novak, Scott P; Glasheen, Cristie; Saccone, Nancy L; Rice, John P; Moreau, Michael P; Doheny, Kimberly F; Romm, Jane M; Brooks, Andrew I; Aouizerat, Bradley E; Bierut, Laura J; Kral, Alex H

    2015-01-01

    Fifty percent of variability in HIV-1 susceptibility is attributable to host genetics. Thus identifying genetic associations is essential to understanding pathogenesis of HIV-1 and important for targeting drug development. To date, however, CCR5 remains the only gene conclusively associated with HIV acquisition. To identify novel host genetic determinants of HIV-1 acquisition, we conducted a genome-wide association study among a high-risk sample of 3,136 injection drug users (IDUs) from the Urban Health Study (UHS). In addition to being IDUs, HIV-controls were frequency-matched to cases on environmental exposures to enhance detection of genetic effects. We tested independent replication in the Women's Interagency HIV Study (N=2,533). We also examined publicly available gene expression data to link SNPs associated with HIV acquisition to known mechanisms affecting HIV replication/infectivity. Analysis of the UHS nominated eight genetic regions for replication testing. SNP rs4878712 in FRMPD1 met multiple testing correction for independent replication (P=1.38x10(-4)), although the UHS-WIHS meta-analysis p-value did not reach genome-wide significance (P=4.47x10(-7) vs. P<5.0x10(-8)) Gene expression analyses provided promising biological support for the protective G allele at rs4878712 lowering risk of HIV: (1) the G allele was associated with reduced expression of FBXO10 (r=-0.49, P=6.9x10(-5)); (2) FBXO10 is a component of the Skp1-Cul1-F-box protein E3 ubiquitin ligase complex that targets Bcl-2 protein for degradation; (3) lower FBXO10 expression was associated with higher BCL2 expression (r=-0.49, P=8x10(-5)); (4) higher basal levels of Bcl-2 are known to reduce HIV replication and infectivity in human and animal in vitro studies. These results suggest new potential biological pathways by which host genetics affect susceptibility to HIV upon exposure for follow-up in subsequent studies.

  20. Sustained NF-kappaB activity in chronic lymphocytic leukemia is independent of genetic and epigenetic alterations in the TNFAIP3 (A20) locus.

    PubMed

    Frenzel, Lukas P; Claus, Rainer; Plume, Nadine; Schwamb, Janine; Konermann, Carolin; Pallasch, Christian P; Claasen, Julia; Brinker, Reinhild; Wollnik, Bernd; Plass, Christoph; Wendtner, Clemens-Martin

    2011-05-15

    Inappropriate nuclear factor (NF) κB activity is one major hallmark of B-cell malignancies and chronic lymphocytic leukemia (CLL). NFκB-dependent genes are involved in antiapoptosis, cell proliferation and metastasis and are responsible for survival and proliferation of tumors. However, the mechanisms of NFκB activity in CLL still need to be elucidated. Previously, we identified translocations in a region on chromosome 6q that encodes tumor necrosis factor alpha-induced protein 3, which is a key player in negative feedback loop regulation of NFκB. Inactivation of this ubiquitin-editing enzyme is involved in immunopathologies and in tumorigenesis. Frequent mutations in the A20 locus--leading to sustained NFκB activity--could be shown to play a dominant role in development of different B-cell malignancies. To check if A20 is involved in upregulation of NFκB activity in CLL, we sequenced Exons 2-9 of the A20 gene in 55 CLL DNA samples. Furthermore, we determined the methylation status of the promoter region in 63 CLL DNA samples and compared to 10 control DNAs of B cells from healthy donors. Contrary to reports from other B-cell malignancies, the A20 region showed neither mutations nor aberrant DNA methylation. Moreover, its expression could be confirmed by immunoblotting and showing comparable results to healthy B cells. These results indicate that malignant development in CLL differs from most of other B-cell malignancies, which show frequent inactivation of A20.

  1. 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

  2. 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.

  3. A low frequency variant within the GWAS locus of MTNR1B affects fasting glucose concentrations: genetic risk is modulated by obesity.

    PubMed

    Been, L F; Hatfield, J L; Shankar, A; Aston, C E; Ralhan, S; Wander, G S; Mehra, N K; Singh, J R; Mulvihill, J J; Sanghera, D K

    2012-11-01

    Two common variants (rs1387153, rs10830963) in MTNR1B have been reported to have independent effects on fasting blood glucose (FBG) levels with increased risk to type 2 diabetes (T2D) in recent genome-wide association studies (GWAS). In this investigation, we report the association of these two variants, and an additional variant (rs1374645) within the GWAS locus of MTNR1B with FBG, 2h glucose, insulin resistance (HOMA IR), β-cell function (HOMA B), and T2D in our sample of Asian Sikhs from India. Our cohort comprised 2222 subjects [1201 T2D, 1021 controls]. None of these SNPs was associated with T2D in this cohort. Our data also could not confirm association of rs1387153 and rs10830963 with FBG phenotype. However, upon stratifying data according to body mass index (BMI) (low ≤ 25 kg/m(2) and high > 25 kg/m(2)) in normoglycemic subjects (n = 1021), the rs1374645 revealed a strong association with low FBG levels in low BMI group (β = -0.073, p = 0.002, Bonferroni p = 0.01) compared to the high BMI group (β = 0.015, p = 0.50). We also detected a strong evidence of interaction between rs1374645 and BMI with respect to FBG levels (p = 0.002). Our data provide new information about the significant impact of another MTNR1B variant on FBG levels that appears to be modulated by BMI. Future confirmation on independent datasets and functional studies will be required to define the role of this variant in fasting glucose variation.

  4. Human high-altitude adaptation: forward genetics meets the HIF pathway

    PubMed Central

    Bigham, Abigail W.

    2014-01-01

    Humans have adapted to the chronic hypoxia of high altitude in several locations, and recent genome-wide studies have indicated a genetic basis. In some populations, genetic signatures have been identified in the hypoxia-inducible factor (HIF) pathway, which orchestrates the transcriptional response to hypoxia. In Tibetans, they have been found in the HIF2A (EPAS1) gene, which encodes for HIF-2α, and the prolyl hydroxylase domain protein 2 (PHD2, also known as EGLN1) gene, which encodes for one of its key regulators, PHD2. High-altitude adaptation may be due to multiple genes that act in concert with one another. Unraveling their mechanism of action can offer new therapeutic approaches toward treating common human diseases characterized by chronic hypoxia. PMID:25319824

  5. Gene therapy for inherited muscle diseases: where genetics meets rehabilitation medicine.

    PubMed

    Braun, Robynne; Wang, Zejing; Mack, David L; Childers, Martin K

    2014-11-01

    The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus vectors are attractive for clinical use because (1) adeno-associated viruses do not cause human disease and (2) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety, and efficacy of gene therapy with adeno-associated virus for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, recent advances in the application of gene therapies to treat inherited muscle disorders are presented, including Duchenne muscular dystrophy and x-linked myotubular myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed.

  6. Proteomics meets genetics: SILAC labeling of Drosophila melanogaster larvae and cells for in vivo functional studies.

    PubMed

    Cuomo, Alessandro; Sanfilippo, Roberta; Vaccari, Thomas; Bonaldi, Tiziana

    2014-01-01

    Stable isotope labeling by amino acids in cell culture (SILAC) is an established and potent method for quantitative proteomics. When combined with high-resolution mass spectrometry (MS) and efficient algorithms for the analysis of quantitative MS data, SILAC has proven to be the strategy of choice for the in-depth characterization of functional states at the protein level. The fruit fly Drosophila melanogaster is one of the most widely used model systems for studies of genetics and developmental biology. Despite this, a global proteomic approach in Drosophila is rarely considered. Here, we describe an adaptation of SILAC for functional investigation of fruit flies by proteomics: We illustrate how to perform efficient SILAC labeling of cells in culture and whole fly larvae. The combination of SILAC, a highly accurate global protein quantification method, and of the fruit fly, the prime genetics and developmental model, represents a unique opportunity for quantitative proteomic studies in vivo.

  7. The society for craniofacial genetics and developmental biology 38th annual meeting.

    PubMed

    Taneyhill, Lisa A; Hoover-Fong, Julie; Lozanoff, Scott; Marcucio, Ralph; Richtsmeier, Joan T; Trainor, Paul A

    2016-07-01

    The mission of the Society for Craniofacial Genetics and Developmental Biology (SCGDB) is to promote education, research, and communication about normal and abnormal development of the tissues and organs of the head. The SCGDB welcomes as members undergraduate students, graduate students, post doctoral researchers, clinicians, orthodontists, scientists, and academicians who share an interest in craniofacial biology. Each year our members come together to share their novel findings, build upon, and challenge current knowledge of craniofacial biology. © 2016 Wiley Periodicals, Inc.

  8. 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.

  9. Tetralogy of Fallot and Hypoplastic Left Heart Syndrome – Complex Clinical Phenotypes Meet Complex Genetic Networks

    PubMed Central

    Lahm, Harald; Schön, Patric; Doppler, Stefanie; Dreßen, Martina; Cleuziou, Julie; Deutsch, Marcus-André; Ewert, Peter; Lange, Rüdiger; Krane, Markus

    2015-01-01

    In many cases congenital heart disease (CHD) is represented by a complex phenotype and an array of several functional and morphological cardiac disorders. These malformations will be briefly summarized in the first part focusing on two severe CHD phenotypes, hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). In most cases of CHD the genetic origin remains largely unknown, though the complexity of the clinical picture strongly argues against a dysregulation which can be attributed to a single candidate gene but rather suggests a multifaceted polygenetic origin with elaborate interactions. Consistent with this idea, genome-wide approaches using whole exome sequencing, comparative sequence analysis of multiplex families to identify de novo mutations and global technologies to identify single nucleotide polymorphisms, copy number variants, dysregulation of the transcriptome and epigenetic variations have been conducted to obtain information about genetic alterations and potential predispositions possibly linked to the occurrence of a CHD phenotype. In the second part of this review we will summarize and discuss the available literature on identified genetic alterations linked to TOF and HLHS. PMID:26069455

  10. The First Genetic and Comparative Map of White Lupin (Lupinus albus L.): Identification of QTLs for Anthracnose Resistance and Flowering Time, and a Locus for Alkaloid Content

    PubMed Central

    Phan, Huyen T. T.; Ellwood, Simon R.; Adhikari, Kedar; Nelson, Matthew N.; Oliver, Richard P.

    2007-01-01

    Abstract We report the first genetic linkage map of white lupin (Lupinus albus L.). An F8 recombinant inbred line population developed from Kiev mutant × P27174 was mapped with 220 amplified fragment length polymorphism and 105 gene-based markers. The genetic map consists of 28 main linkage groups (LGs) that varied in length from 22.7 cM to 246.5 cM and spanned a total length of 2951 cM. There were seven additional pairs and 15 unlinked markers, and 12.8% of markers showed segregation distortion at P < 0.05. Syntenic relationships between Medicago truncatula and L. albus were complex. Forty-five orthologous markers that mapped between M. truncatula and L. albus identified 17 small syntenic blocks, and each M. truncatula chromosome aligned to between one and six syntenic blocks in L. albus. Genetic mapping of three important traits: anthracnose resistance, flowering time, and alkaloid content allowed loci governing these traits to be defined. Two quantitative trait loci (QTLs) with significant effects were identified for anthracnose resistance on LG4 and LG17, and two QTLs were detected for flowering time on the top of LG1 and LG3. Alkaloid content was mapped as a Mendelian trait to LG11. PMID:17526914

  11. 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

  12. Multi-Locus Analysis Reveals A Different Pattern of Genetic Diversity for Mitochondrial and Nuclear DNA between Wild and Domestic Pigs in East Asia

    PubMed Central

    Ji, Yin-Qiu; Wu, Dong-Dong; Wu, Gui-Sheng; Wang, Guo-Dong; Zhang, Ya-Ping

    2011-01-01

    Background A major reduction of genetic diversity in mtDNA occurred during the domestication of East Asian pigs. However, the extent to which genetic diversity has been lost in the nuclear genome is uncertain. To reveal levels and patterns of nucleotide diversity and to elucidate the genetic relationships and demographic history of domestic pigs and their ancestors, wild boars, we investigated 14 nuclear markers (including 8 functional genes, 2 pseudogenes and 4 intergenic regions) from 11 different chromosomes in East Asia-wide samples and pooled them with previously obtained mtDNA data for a combined analysis. Principal Findings The results indicated that domestic pigs and wild boars possess comparable levels of nucleotide diversity across the nuclear genome, which is inconsistent with patterns that have been found in mitochondrial genome. Conclusions This incongruence between the mtDNA and nuclear genomes is suggestive of a large-scale backcross between male wild boars and female domestic pigs in East Asia. Our data reveal the impacts of founder effects and backcross on the pig genome and help us better understand the complex demographic histories of East Asian pigs, which will be useful for future work on artificial selection. PMID:22065995

  13. Genetic map construction and quantitative trait locus (QTL) detection of growth-related traits in Litopenaeus vannamei for selective breeding applications.

    PubMed

    Andriantahina, Farafidy; Liu, Xiaolin; Huang, Hao

    2013-01-01

    Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL) have been regarded as useful for marker-assisted selection (MAS) in complex traits as growth. Using an intermediate F2 cross of slow and fast growth parents, a genetic linkage map of Pacific whiteleg shrimp, Litopenaeusvannamei, based on amplified fragment length polymorphisms (AFLP) and simple sequence repeats (SSR) markers was constructed. Meanwhile, QTL analysis was performed for growth-related traits. The linkage map consisted of 451 marker loci (429 AFLPs and 22 SSRs) which formed 49 linkage groups with an average marker space of 7.6 cM; they spanned a total length of 3627.6 cM, covering 79.50% of estimated genome size. 14 QTLs were identified for growth-related traits, including three QTLs for body weight (BW), total length (TL) and partial carapace length (PCL), two QTLs for body length (BL), one QTL for first abdominal segment depth (FASD), third abdominal segment depth (TASD) and first abdominal segment width (FASW), which explained 2.62 to 61.42% of phenotypic variation. Moreover, comparison of linkage maps between L. vannamei and Penaeusjaponicus was applied, providing a new insight into the genetic base of QTL affecting the growth-related traits. The new results will be useful for conducting MAS breeding schemes in L. vannamei .

  14. Genetic Map Construction and Quantitative Trait Locus (QTL) Detection of Six Economic Traits Using an F2 Population of the Hybrid from Saccharina longissima and Saccharina japonica.

    PubMed

    Zhang, Jing; Liu, Tao; Feng, Rongfang; Liu, Cui; Chi, Shan

    2015-01-01

    Saccharina (Laminaria) is one of the most important economic seaweeds. Previously, four genetic linkage maps of Saccharina have been constructed and five QTLs have been identified. However, they were not enough for its breeding. In this work, Saccharina longissima (♀) and Saccharina japonica (♂), which showed obvious differences in morphology and genetics, were applied in hybridization to yield the F2 mapping population with 102 individuals. Using these 102 F2 hybrids, the genetic linkage map of Saccharina was constructed by MapMaker software based on 37 amplified fragment length polymorphisms (AFLPs), 22 sequence-related amplified polymorphisms (SRAPs) and 139 simple sequence repeats (SSRs) markers. Meanwhile, QTL analysis was performed for six economic traits. The linkage map constructed in this research consisted of 422 marker loci (137 AFLPs, 57 SRAPs and 228 SSRs), which formed 45 linkage groups (LGs) with an average marker space of 7.92 cM; they spanned a total length of 2233.1 cM, covering the whole estimated genome size. A total of 29 QTLs were identified for six economic traits, which explained 1.06 to 64.00% of phenotypic variation, including three QTLs for frond length (FL) and raw weight (RW), five QTLs for frond width (FW), two QTLs for frond fascia width (FFW) and frond thickness (FT), and fourteen QTLs for base shape (BS). The results of this research will improve the breeding efficiency and be beneficial for marker-assisted selection (MAS) schemes in Saccharina breeding.

  15. Specific-locus mutation rates in the mouse following inhalation of ethylene oxide, and application of the results to estimation of human genetic risk.

    PubMed

    Russell, L B; Cumming, R B; Hunsicker, P R

    1984-12-01

    Male (101 X C3H)F1 mice were exposed in an inhalation chamber to ethylene oxide (EtO) in air at a concentration of (generally) 255 ppm. After accumulating total exposures of 101 000 or 150 000 ppm.h in 16-23 weeks, the males were mated to T-stock females for a standard specific-locus mutation-rate study in which 71387 offspring were observed. The spermatogonial stem-cell mutation rate at each exposure level, as well as the combined result, does not differ significantly from the historical control frequency. At the lower and higher exposure levels, the results rule out (at the 5% significance level) an induced frequency that is, respectively, 0.97 and 6.33 times the spontaneous rate; the combined results rule out a multiple of 1.64. The relationship between mouse spermatogonial stem-cell mutation rates and EtO-induced testis ethylations was compared with the relationship between Drosophila post-stem-cell mutation rates and sperm ethylations (Lee, 1980). The comparison does not rule out equal mutability per ethylation; but it cannot prove parallelism. An assessment of the mouse-Drosophila relationship will require a more efficient alkylator than EtO and the use of comparable germ-cell stages. More meaningful conclusions may be drawn by utilizing the data for direct estimation of human risk by expressing the induced mutation frequency that is ruled out (at the 5% significance level) as a multiple of control rate and extrapolating to human exposure levels. The probable absence of major stem-cell killing (and thus, possibly, cell selection) by EtO indicates that such extrapolation probably does not produce an underestimate. For a human exposure concentration of 0.1 ppm on working days during the reproductive lifespan, the mouse experimental results rule out (at the 5% significance level) an induced spermatogonial stem-cell gene mutation rate greater than 8% of the spontaneous rate; for 1.0 ppm, they rule out an induced rate roughly equal to the spontaneous rate. The

  16. High Frequency of Copy Number Variations and Sequence Variants at CYP21A2 Locus: Implication for the Genetic Diagnosis of 21-Hydroxylase Deficiency

    PubMed Central

    Parajes, Silvia; Quinteiro, Celsa; Domínguez, Fernando; Loidi, Lourdes

    2008-01-01

    Background The systematic study of the human genome indicates that the inter-individual variability is greater than expected and it is not only related to sequence polymorphisms but also to gene copy number variants (CNVs). Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most common autosomal recessive disorder with a carrier frequency of 1∶25 to 1∶10. The gene that encodes 21-hydroxylase enzyme, CYP21A2, is considered to be one of the most polymorphic human genes. Copy number variations, such as deletions, which are severe mutations common in 21OHD patients, or gene duplications, which have been reported as rare events, have also been described. The correct characterization of 21OHD alleles is important for disease carrier detection and genetic counselling Methodology and Findings CYP21A2 genotyping by sequencing has been performed in a random sample of the Spanish population, where 144 individuals recruited from university students and employees of the hospital were studied. The frequency of CYP21A2 mutated alleles in our sample was 15.3% (77.3% were mild mutations, 9% were severe mutations and 13.6% were novel variants). Gene dosage assessment was also performed when CYP21A2 gene duplication was suspected. This analysis showed that 7% of individuals bore a chromosome with a duplicated CYP21A2 gene, where one of the copies was mutated. Conclusions As far as we know, the present study has shown the highest frequency of 21OHD carriers reported by a genotyping analysis. In addition, a high frequency of alleles with CYP21A2 duplications, which could be misinterpreted as 21OHD alleles, was found. Moreover, a high frequency of novel genetic variations with an unknown effect on 21-hydroxylase activity was also found. The high frequency of gene duplications, as well as novel variations, should be considered since they have an important involvement in carrier testing and genetic counseling. PMID:18478071

  17. Identification of shared genetic susceptibility locus for coronary artery disease, type 2 diabetes and obesity: a meta-analysis of genome-wide studies.

    PubMed

    Wu, Chaoneng; Gong, Yunguo; Yuan, Jie; Gong, Hui; Zou, Yunzeng; Ge, Junbo

    2012-06-14

    Type 2 diabetes (2DM), obesity, and coronary artery disease (CAD) are frequently coexisted being as key components of metabolic syndrome. Whether there is shared genetic background underlying these diseases remained unclear. We performed a meta-analysis of 35 genome screens for 2DM, 36 for obesity or body mass index (BMI)-defined obesity, and 21 for CAD using genome search meta-analysis (GSMA), which combines linkage results to identify regions with only weak evidence and provide genetic interactions among different diseases. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to the best linkage evidence within each bin. For each disease, bin 6.2 achieved genomic significanct evidence, and bin 9.3, 10.5, 16.3 reached suggestive level for 2DM. Bin 11.2 and 16.3, and bin 10.5 and 9.3, reached suggestive evidence for obesity and CAD respectively. In pooled all three diseases, bin 9.3 and 6.5 reached genomic significant and suggestive evidence respectively, being relatively much weaker for 2DM/CAD or 2DM/obesity or CAD/obesity. Further, genomewide significant evidence was observed of bin 16.3 and 4.5 for 2DM/obesity, which is decreased when CAD was added. These findings indicated that bin 9.3 and 6.5 are most likely to be shared by 2DM, obesity and CAD. And bin 16.3 and 4.5 are potentially common regions to 2DM and obesity only. The observed shared susceptibility regions imply a partly overlapping genetic aspects of disease development. Fine scanning of these regions will definitely identify more susceptibility genes and causal variants.

  18. Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations

    PubMed Central

    Ganz, Ariel B.; Cohen, Vanessa V.; Swersky, Camille C.; Stover, Julie; Vitiello, Gerardo A.; Lovesky, Jessica; Chuang, Jasmine C.; Shields, Kelsey; Fomin, Vladislav G.; Lopez, Yusnier S.; Mohan, Sanjay; Ganti, Anita; Carrier, Bradley; Malysheva, Olga V.; Caudill, Marie A.

    2017-01-01

    Single nucleotide polymorphisms (SNPs) in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75) consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9) for 10–12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP)-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT) denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term. PMID:28134761

  19. Monster potential meets potential monster: pros and cons of deploying genetically modified microalgae for biofuels production.

    PubMed

    Flynn, K J; Mitra, A; Greenwell, H C; Sui, J

    2013-02-06

    Biofuels production from microalgae attracts much attention but remains an unproven technology. We explore routes to enhance production through modifications to a range of generic microalgal physiological characteristics. Our analysis shows that biofuels production may be enhanced ca fivefold through genetic modification (GM) of factors affecting growth rate, respiration, photoacclimation, photosynthesis efficiency and the minimum cell quotas for nitrogen and phosphorous (N : C and P : C). However, simulations indicate that the ideal GM microalgae for commercial deployment could, on escape to the environment, become a harmful algal bloom species par excellence, with attendant risks to ecosystems and livelihoods. In large measure, this is because an organism able to produce carbohydrate and/or lipid at high rates, providing stock metabolites for biofuels production, will also be able to attain a stoichiometric composition that will be far from optimal as food for the support of zooplankton growth. This composition could suppress or even halt the grazing activity that would otherwise control the microalgal growth in nature. In consequence, we recommend that the genetic manipulation of microalgae, with inherent consequences on a scale comparable to geoengineering, should be considered under strict international regulation.

  20. Monster potential meets potential monster: pros and cons of deploying genetically modified microalgae for biofuels production

    PubMed Central

    Flynn, K. J.; Mitra, A.; Greenwell, H. C.; Sui, J.

    2013-01-01

    Biofuels production from microalgae attracts much attention but remains an unproven technology. We explore routes to enhance production through modifications to a range of generic microalgal physiological characteristics. Our analysis shows that biofuels production may be enhanced ca fivefold through genetic modification (GM) of factors affecting growth rate, respiration, photoacclimation, photosynthesis efficiency and the minimum cell quotas for nitrogen and phosphorous (N : C and P : C). However, simulations indicate that the ideal GM microalgae for commercial deployment could, on escape to the environment, become a harmful algal bloom species par excellence, with attendant risks to ecosystems and livelihoods. In large measure, this is because an organism able to produce carbohydrate and/or lipid at high rates, providing stock metabolites for biofuels production, will also be able to attain a stoichiometric composition that will be far from optimal as food for the support of zooplankton growth. This composition could suppress or even halt the grazing activity that would otherwise control the microalgal growth in nature. In consequence, we recommend that the genetic manipulation of microalgae, with inherent consequences on a scale comparable to geoengineering, should be considered under strict international regulation. PMID:24427510

  1. Recommendations from a meeting on health implications of genetically modified organism (GMO).

    PubMed

    Amofah, George

    2014-06-01

    The Ghana Public Health Association organized a scientific seminar to examine the introduction of genetically modified organisms into public use and the health consequences. The seminar was driven by current public debate on the subject. The seminar identified some of the advantages of GMOs and also the health concerns. It is clear that there is the need to enhance local capacity to research the introduction and use of GMOs; to put in place appropriate regulatory mechanisms including particularly the labeling of GMO products and post-marketing surveillance for possible negative health consequences in the long term. Furthermore the appropriate state agency should put in place advocacy strategies to keep the public informed about GMOs.

  2. The HIF1A functional genetic polymorphism at locus +1772 associates with progression to metastatic prostate cancer and refractoriness to hormonal castration.

    PubMed

    Fraga, Avelino; Ribeiro, Ricardo; Príncipe, Paulo; Lobato, Carlos; Pina, Francisco; Maurício, Joaquina; Monteiro, Cátia; Sousa, Hugo; Calais da Silva, F; Lopes, Carlos; Medeiros, Rui

    2014-01-01

    The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT.

  3. Genetic Analysis Using an Isogenic Mating Pair of Aspergillus fumigatus Identifies Azole Resistance Genes and Lack of MAT Locus's Role in Virulence.

    PubMed

    Losada, Liliana; Sugui, Janyce A; Eckhaus, Michael A; Chang, Yun C; Mounaud, Stephanie; Figat, Abigail; Joardar, Vinita; Pakala, Suman B; Pakala, Suchitra; Venepally, Pratap; Fedorova, Natalie; Nierman, William C; Kwon-Chung, Kyung J

    2015-04-01

    Invasive aspergillosis (IA) due to Aspergillus fumigatus is a major cause of mortality in immunocompromised patients. The discovery of highly fertile strains of A. fumigatus opened the possibility to merge classical and contemporary genetics to address key questions about this pathogen. The merger involves sexual recombination, selection of desired traits, and genomics to identify any associated loci. We constructed a highly fertile isogenic pair of A. fumigatus strains with opposite mating types and used them to investigate whether mating type is associated with virulence and to find the genetic loci involved in azole resistance. The pair was made isogenic by 9 successive backcross cycles of the foundational strain AFB62 (MAT1-1) with a highly fertile (MAT1-2) progeny. Genome sequencing showed that the F9 MAT1-2 progeny was essentially identical to the AFB62. The survival curves of animals infected with either strain in three different animal models showed no significant difference, suggesting that virulence in A. fumigatus was not associated with mating type. We then employed a relatively inexpensive, yet highly powerful strategy to identify genomic loci associated with azole resistance. We used traditional in vitro drug selection accompanied by classical sexual crosses of azole-sensitive with resistant isogenic strains. The offspring were plated under varying drug concentrations and pools of resulting colonies were analyzed by whole genome sequencing. We found that variants in 5 genes contributed to azole resistance, including mutations in erg11A (cyp51A), as well as multi-drug transporters, erg25, and in HMG-CoA reductase. The results demonstrated that with minimal investment into the sequencing of three pools from a cross of interest, the variation(s) that contribute any phenotype can be identified with nucleotide resolution. This approach can be applied to multiple areas of interest in A. fumigatus or other heterothallic pathogens, especially for virulence

  4. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  5. Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics

    PubMed Central

    Villar-Piqué, Anna; Rossetti, Giulia; Ventura, Salvador; Carloni, Paolo; Fernández, Claudio O.; Outeiro, Tiago Fleming

    2017-01-01

    ABSTRACT Copper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is still unclear. Previous studies suggested that this residue does not significantly affect copper-mediated aSyn aggregation. However, our findings showed that the aggregation of the pathological H50Q aSyn mutant is enhanced by copper hints otherwise. Despite the inexistence of a model for aSyn H50Q-copper complexation, we discuss possible mechanisms by which this metal contributes to the misfolding and self-assembly of this particular aSyn mutant. Considering the genetic association of the H50Q mutation with familial forms of Parkinson disease, and the fact that copper homeostasis is deregulated in this disorder, understanding the interplay between both factors will shed light into the molecular and cellular mechanisms triggering the development and spreading of the aSyn pathology. PMID:28289488

  6. Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application.

    PubMed

    Alapati, Deepthi; Morrisey, Edward E

    2017-03-01

    Although our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis, and alpha-1 antitrypsin deficiency is extensive, treatment options are lacking. Because the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intratracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene-editing technology is a promising approach to repairing or inactivating disease-causing mutations. Recent reports have provided proof of concept by using CRISPR/Cas9 to successfully repair or inactivate mutations in animal models of monogenic human diseases. Potential pulmonary applications of CRISPR/Cas9 gene editing include gene correction of monogenic diseases in pre- or postnatal lungs and ex vivo gene editing of patient-specific airway stem cells followed by autologous cell transplant. Strategies to enhance gene-editing efficiency and eliminate off-target effects by targeting pulmonary stem/progenitor cells and the assessment of short-term and long-term effects of gene editing are important considerations as the field advances. If methods continue to advance rapidly, CRISPR/Cas9-mediated gene editing may provide a novel opportunity to correct monogenic diseases of the respiratory system.

  7. Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics.

    PubMed

    Villar-Piqué, Anna; Rossetti, Giulia; Ventura, Salvador; Carloni, Paolo; Fernández, Claudio O; Outeiro, Tiago Fleming

    2017-01-01

    Copper is one of the metals described to bind the Parkinson disease-related protein α-synuclein (aSyn), and to promote its aggregation. Although histidine at position 50 in the aSyn sequence is one of the most studied copper-anchoring sites, its precise role in copper binding and aSyn aggregation is still unclear. Previous studies suggested that this residue does not significantly affect copper-mediated aSyn aggregation. However, our findings showed that the aggregation of the pathological H50Q aSyn mutant is enhanced by copper hints otherwise. Despite the inexistence of a model for aSyn H50Q-copper complexation, we discuss possible mechanisms by which this metal contributes to the misfolding and self-assembly of this particular aSyn mutant. Considering the genetic association of the H50Q mutation with familial forms of Parkinson disease, and the fact that copper homeostasis is deregulated in this disorder, understanding the interplay between both factors will shed light into the molecular and cellular mechanisms triggering the development and spreading of the aSyn pathology.

  8. Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study.

    PubMed

    Das, Mithun; Sha, Jin; Hidalgo, Bertha; Aslibekyan, Stella; Do, Anh N; Zhi, Degui; Sun, Dianjianyi; Zhang, Tao; Li, Shengxu; Chen, Wei; Srinivasan, Sathanur R; Tiwari, Hemant K; Absher, Devin; Ordovas, Jose M; Berenson, Gerald S; Arnett, Donna K; Irvin, Marguerite R

    2016-01-01

    In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10(-7) was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10(-14) and P for cg17058475 = 1.2x10(-9)). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.

  9. Report on the 6th African Society of Human Genetics (AfSHG) Meeting, March 12–15, 2009, Yaoundé, Cameroon

    PubMed Central

    Sirugo, Giorgio; Williams, Scott M.; Royal, Charmaine D. M.; Newport, Melanie J.; Hennig, Branwen J.; Mariani-Costantini, Renato; Buonaguro, Franco M.; Velez Edwards, Digna R.; Ibrahim, Muntaser; Soodyall, Himla; Wonkam, Ambroise; Ramesar, Raj; Rotimi, Charles N.

    2010-01-01

    The African Society of Human Genetics (AfSHG), founded in 2003 with its inaugural meeting in Accra, Ghana,1 has the stated missions of (1) disseminating information about human genetics research in Africa, (2) establishing a mentorship network providing educational resources, including the development of appropriate technology transfer, (3) providing advocacy for human genetic research in Africa, and (4) encouraging collaborative research. Despite its young age, the AfSHG has developed a strong cadre of active researchers, both within and outside of Africa, with more than 400 members (from 16 countries across Africa as well as 8 other countries), and has held six successful meetings, five in Africa and one in the United States. PMID:20682860

  10. Development of a multiple-locus variable-number tandem-repeat typing scheme for genetic fingerprinting of Burkholderia cenocepacia and application to nationwide epidemiological analysis.

    PubMed

    Segonds, Christine; Thouverez, Michelle; Barthe, Antoine; Bossuet-Greif, Nadège; Tisseyre, Lenka; Plésiat, Patrick; Vergnaud, Gilles; Chabanon, Gérard; Pourcel, Christine

    2015-02-01

    Organisms of the Burkholderia cepacia complex are especially important pathogens in cystic fibrosis (CF), with a propensity for patient-to-patient spread and long-term respiratory colonization. B. cenocepacia and Burkholderia multivorans account for the majority of infections in CF, and major epidemic clones have been recognized throughout the world. The aim of the present study was to develop and evaluate a multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) scheme for B. cenocepacia. Potential VNTR loci were identified upon analysis of the annotated genome sequences of B. cenocepacia strains AU1054, J2315, and MCO-3, and 10 of them were selected on the basis of polymorphisms and size. A collection of 100 B. cenocepacia strains, including epidemiologically related and unrelated strains, as well as representatives of the major epidemic lineages, was used to evaluate typeability, epidemiological concordance, and the discriminatory power of MLVA-10 compared with those of pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Longitudinal stability was assessed by testing 39 successive isolates from 14 patients. Typeability ranged from 0.91 to 1, except for that of one marker, which was not amplified in 53% of the B. cenocepacia IIIA strains. The MLVA types were shown to be stable in chronically colonized patients and within outbreak-related strains, with excellent epidemiological concordance. Epidemic and/or globally distributed lineages (epidemic Edinburgh-Toronto electrophoretic type 12 [ET-12], sequence type 32 [ST-32], ST-122, ST-234, and ST-241) were successfully identified. Conversely, the discriminatory power of MLVA was lower than that of PFGE or MLST, although PFGE variations within the epidemic lineages sometimes masked their genetic relatedness. In conclusion, MLVA represents a promising cost-effective first-line tool in B. cenocepacia surveillance.

  11. Quantitative trait locus mapping based on resampling in a vast maize testcross experiment and its relevance to quantitative genetics for complex traits.

    PubMed

    Schön, Chris C; Utz, H Friedrich; Groh, Susanne; Truberg, Bernd; Openshaw, Steve; Melchinger, Albrecht E

    2004-05-01

    From simulation studies it is known that the allocation of experimental resources has a crucial effect on power of QTL detection as well as on accuracy and precision of QTL estimates. In this study, we used a very large experimental data set composed of 976 F(5) maize testcross progenies evaluated in 19 environments and cross-validation to assess the effect of sample size (N), number of test environments (E), and significance threshold on the number of detected QTL, the proportion of the genotypic variance explained by them, and the corresponding bias of estimates for grain yield, grain moisture, and plant height. In addition, we used computer simulations to compare the usefulness of two cross-validation schemes for obtaining unbiased estimates of QTL effects. The maximum, validated genotypic variance explained by QTL in this study was 52.3% for grain moisture despite the large number of detected QTL, thus confirming the infinitesimal model of quantitative genetics. In both simulated and experimental data, the effect of sample size on power of QTL detection as well as on accuracy and precision of QTL estimates was large. The number of detected QTL and the proportion of genotypic variance explained by QTL generally increased more with increasing N than with increasing E. The average bias of QTL estimates and its range were reduced by increasing N and E. Cross-validation performed well with respect to yielding asymptotically unbiased estimates of the genotypic variance explained by QTL. On the basis of our findings, recommendations for planning of QTL mapping experiments and allocation of experimental resources are given.

  12. The IGF2 Locus

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Genome-Wide Linkage Screen for Systolic Blood Pressure in the Veterans Administration Genetic Epidemiology Study (VAGES) of Mexican-Americans and Confirmation of a Major Susceptibility Locus on Chromosome 6q14.1

    PubMed Central

    Puppala, Sobha; Coletta, Dawn K.; Schneider, Jennifer; Hu, Shirley L.; Farook, Vidya S.; Dyer, Thomas D.; Arya, Rector; Blangero, John; Duggirala, Ravindranath; DeFronzo, Ralph A.; Jenkinson, Christopher P.

    2011-01-01

    Objective Hypertension or high blood pressure is a strong correlate of diseases such as obesity and type 2 diabetes. We conducted a genome-wide linkage screen to identify susceptibility genes influencing systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Mexican-Americans from the Veterans Administration Genetic Epidemiology Study (VAGES). Methods Using data from 1,089 individuals distributed across 266 families, we performed a multipoint linkage analysis to localize susceptibility loci for SBP and DBP by applying two models. In model 1, we added a sensible constant to the observed BP values in treated subjects [Tobin et al.; Stat Med 2005;24:2911–2935] to account for antihypertensive use (i.e. 15 and 10 mm Hg to SBP and DBP values, respectively). In model 2, we fixed values of 140 mm Hg for SBP and 90 mm Hg for DBP, if the treated values were less than the standard referenced treatment thresholds of 140/90 mm Hg for hypertensive status. However, if the observed treated BP values were found to be above these standard treatment thresholds, the actual observed treated BP values were retained in order not to reduce them by substitution of the treatment threshold values. Results The multipoint linkage analysis revealed strong linkage signals for SBP compared with DBP. The strongest evidence for linkage of SBP (model 1, LOD = 5.0; model 2, LOD = 3.6) was found on chromosome 6q14.1 near the marker D6S1031 (89 cM) in both models. In addition, some evidence for SBP linkage occurred on chromosomes 1q, 4p, and 16p. Most importantly, our major SBP linkage finding on chromosome 6q near marker D6S1031 was independently confirmed in a Caucasian population (LOD = 3.3). In summary, our study found evidence for a major locus on chromosome 6q influencing SBP levels in Mexican-Americans. PMID:21293138

  14. Genetic Analysis of Strawberry Fruit Aroma and Identification of O-Methyltransferase FaOMT as the Locus Controlling Natural Variation in Mesifurane Content1[C][W][OA

    PubMed Central

    Zorrilla-Fontanesi, Yasmín; Rambla, José-Luis; Cabeza, Amalia; Medina, Juan J.; Sánchez-Sevilla, José F.; Valpuesta, Victoriano; Botella, Miguel A.; Granell, Antonio; Amaya, Iraida

    2012-01-01

    Improvement of strawberry (Fragaria × ananassa) fruit flavor is an important goal in breeding programs. To investigate genetic factors controlling this complex trait, a strawberry mapping population derived from genotype ‘1392’, selected for its superior flavor, and ‘232’ was profiled for volatile compounds over 4 years by headspace solid phase microextraction coupled to gas chromatography and mass spectrometry. More than 300 volatile compounds were detected, of which 87 were identified by comparison of mass spectrum and retention time to those of pure standards. Parental line ‘1392’ displayed higher volatile levels than ‘232’, and these and many other compounds with similar levels in both parents segregated in the progeny. Cluster analysis grouped the volatiles into distinct chemically related families and revealed a complex metabolic network underlying volatile production in strawberry fruit. Quantitative trait loci (QTL) detection was carried out over 3 years based on a double pseudo-testcross strategy. Seventy QTLs covering 48 different volatiles were detected, with several of them being stable over time and mapped as major QTLs. Loci controlling γ-decalactone and mesifurane content were mapped as qualitative traits. Using a candidate gene approach we have assigned genes that are likely responsible for several of the QTLs. As a proof of concept we show that one homoeolog of the O-methyltransferase gene (FaOMT) is the locus responsible for the natural variation of mesifurane content. Sequence analysis identified 30 bp in the promoter of this FaOMT homoeolog containing putative binding sites for basic/helix-loop-helix, MYB, and BZIP transcription factors. This polymorphism fully cosegregates with both the presence of mesifurane and the high expression of FaOMT during ripening. PMID:22474217

  15. Rapporteur summaries of plenary, symposia, and oral sessions from the XXIIIrd World Congress of Psychiatric Genetics Meeting in Toronto, Canada, 16-20 October 2015.

    PubMed

    Zai, Gwyneth; Alberry, Bonnie; Arloth, Janine; Bánlaki, Zsófia; Bares, Cristina; Boot, Erik; Camilo, Caroline; Chadha, Kartikay; Chen, Qi; Cole, Christopher B; Cost, Katherine T; Crow, Megan; Ekpor, Ibene; Fischer, Sascha B; Flatau, Laura; Gagliano, Sarah; Kirli, Umut; Kukshal, Prachi; Labrie, Viviane; Lang, Maren; Lett, Tristram A; Maffioletti, Elisabetta; Maier, Robert; Mihaljevic, Marina; Mittal, Kirti; Monson, Eric T; O'Brien, Niamh L; Østergaard, Søren D; Ovenden, Ellen; Patel, Sejal; Peterson, Roseann E; Pouget, Jennie G; Rovaris, Diego L; Seaman, Lauren; Shankarappa, Bhagya; Tsetsos, Fotis; Vereczkei, Andrea; Wang, Chenyao; Xulu, Khethelo; Yuen, Ryan K C; Zhao, Jingjing; Zai, Clement C; Kennedy, James L

    2016-12-01

    The XXIIIrd World Congress of Psychiatric Genetics meeting, sponsored by the International Society of Psychiatric Genetics, was held in Toronto, ON, Canada, on 16-20 October 2015. Approximately 700 participants attended to discuss the latest state-of-the-art findings in this rapidly advancing and evolving field. The following report was written by trainee travel awardees. Each was assigned one session as a rapporteur. This manuscript represents the highlights and topics that were covered in the plenary sessions, symposia, and oral sessions during the conference, and contains major notable and new findings.

  16. History of the discovery of a master locus producing piRNAs: the flamenco/COM locus in Drosophila melanogaster.

    PubMed

    Goriaux, Coline; Théron, Emmanuelle; Brasset, Emilie; Vaury, Chantal

    2014-01-01

    The discovery of transposable elements (TEs) in the 1950s by B. McClintock implied the existence of cellular regulatory systems controlling TE activity. The discovery of flamenco (flam) an heterochromatic locus from Drosophila melanogaster and its ability to survey several TEs such as gypsy, ZAM, and Idefix contributed to peer deeply into the mechanisms of the genetic and epigenetic regulation of TEs. flam was the first cluster producing small RNAs to be discovered long before RNAi pathways were identified in 1998. As a result of the detailed genetic analyses performed by certain laboratories and of the sophisticated genetic tools they developed, this locus has played a major role in our understanding of piRNA mediated TE repression in animals. Here we review the first discovery of this locus and retrace decades of studies that led to our current understanding of the relationship between genomes and their TE targets.

  17. History of the discovery of a master locus producing piRNAs: the flamenco/COM locus in Drosophila melanogaster

    PubMed Central

    Coline, Goriaux; Théron, Emmanuelle; Brasset, Emilie; Vaury, Chantal

    2014-01-01

    The discovery of transposable elements (TEs) in the 1950s by B. McClintock implied the existence of cellular regulatory systems controlling TE activity. The discovery of flamenco (flam) an heterochromatic locus from Drosophila melanogaster and its ability to survey several TEs such as gypsy, ZAM, and Idefix contributed to peer deeply into the mechanisms of the genetic and epigenetic regulation of TEs. flam was the first cluster producing small RNAs to be discovered long before RNAi pathways were identified in 1998. As a result of the detailed genetic analyses performed by certain laboratories and of the sophisticated genetic tools they developed, this locus has played a major role in our understanding of piRNA mediated TE repression in animals. Here we review the first discovery of this locus and retrace decades of studies that led to our current understanding of the relationship between genomes and their TE targets. PMID:25136352

  18. IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

    PubMed

    Barbaux, S; Erwich, J J H M; Favaron, P O; Gil, S; Gallot, D; Golos, T G; Gonzalez-Bulnes, A; Guibourdenche, J; Heazell, A E P; Jansson, T; Laprévote, O; Lewis, R M; Miller, R K; Monk, D; Novakovic, B; Oudejans, C; Parast, M; Peugnet, P; Pfarrer, C; Pinar, H; Roberts, C T; Robinson, W; Saffery, R; Salomon, C; Sexton, A; Staff, A C; Suter, M; Tarrade, A; Wallace, J; Vaillancourt, C; Vaiman, D; Worton, S A; Lash, G E

    2015-04-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction.

  19. Tension versus ecological zones in a two-locus system.

    PubMed

    Hu, Xin-Sheng

    2005-08-01

    Previous theories show that tension and ecological zones are indistinguishable in terms of gene frequency clines. Here I analytically show that these two types of zones can be distinguished in terms of genetic statistics other than gene frequency. A two-locus cline model is examined with the assumptions of random mating, weak selection, no drift, no mutation, and multiplicative viabilities. The genetic statistics for distinguishing the two types of zones are the deviations of one- or two-locus genotypic frequencies from Hardy-Weinberg equilibrium (HWE) or from random association of gametes (RAG), and the deviations of additive and dominance variances from the values at HWE. These deviations have a discontinuous distribution in space and different extents of interruptions in the ecological zone with a sharp boundary, but exhibit a continuous distribution in the tension zone. Linkage disequilibrium enhances the difference between the deviations from HWE and from RAG for any two-locus genotypic frequency.

  20. Reminiscences of a mouse specific-locus test addict.

    PubMed

    Russell, W L

    1989-01-01

    This paper describes some of the historical events surrounding the development of and achievements with the mouse specific-locus test in radiation and chemical mutagenesis. Some ongoing and future contributions of the test to research in molecular genetics are also mentioned.

  1. 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.

  2. Strategies for conditional two-locus nonparametric linkage analysis.

    PubMed

    Angquist, Lars; Hössjer, Ola; Groop, Leif

    2008-01-01

    In this article we deal with two-locus nonparametric linkage (NPL) analysis, mainly in the context of conditional analysis. This means that one incorporates single-locus analysis information through conditioning when performing a two-locus analysis. Here we describe different strategies for using this approach. Cox et al. [Nat Genet 1999;21:213-215] implemented this as follows: (i) Calculate the one-locus NPL process over the included genome region(s). (ii) Weight the individual pedigree NPL scores using a weighting function depending on the NPL scores for the corresponding pedigrees at speci fi c conditioning loci. We generalize this by conditioning with respect to the inheritance vector rather than the NPL score and by separating between the case of known (prede fi ned) and unknown (estimated) conditioning loci. In the latter case we choose conditioning locus, or loci, according to prede fi ned criteria. The most general approach results in a random number of selected loci, depending on the results from the previous one-locus analysis. Major topics in this article include discussions on optimal score functions with respect to the noncentrality parameter (NCP), and how to calculate adequate p values and perform power calculations. We also discuss issues related to multiple tests which arise from the two-step procedure with several conditioning loci as well as from the genome-wide tests.

  3. Next-generation sequencing meets genetic diagnostics: development of a comprehensive workflow for the analysis of BRCA1 and BRCA2 genes.

    PubMed

    Feliubadaló, Lídia; Lopez-Doriga, Adriana; Castellsagué, Ester; del Valle, Jesús; Menéndez, Mireia; Tornero, Eva; Montes, Eva; Cuesta, Raquel; Gómez, Carolina; Campos, Olga; Pineda, Marta; González, Sara; Moreno, Victor; Brunet, Joan; Blanco, Ignacio; Serra, Eduard; Capellá, Gabriel; Lázaro, Conxi

    2013-08-01

    Next-generation sequencing (NGS) is changing genetic diagnosis due to its huge sequencing capacity and cost-effectiveness. The aim of this study was to develop an NGS-based workflow for routine diagnostics for hereditary breast and ovarian cancer syndrome (HBOCS), to improve genetic testing for BRCA1 and BRCA2. A NGS-based workflow was designed using BRCA MASTR kit amplicon libraries followed by GS Junior pyrosequencing. Data analysis combined Variant Identification Pipeline freely available software and ad hoc R scripts, including a cascade of filters to generate coverage and variant calling reports. A BRCA homopolymer assay was performed in parallel. A research scheme was designed in two parts. A Training Set of 28 DNA samples containing 23 unique pathogenic mutations and 213 other variants (33 unique) was used. The workflow was validated in a set of 14 samples from HBOCS families in parallel with the current diagnostic workflow (Validation Set). The NGS-based workflow developed permitted the identification of all pathogenic mutations and genetic variants, including those located in or close to homopolymers. The use of NGS for detecting copy-number alterations was also investigated. The workflow meets the sensitivity and specificity requirements for the genetic diagnosis of HBOCS and improves on the cost-effectiveness of current approaches.

  4. 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

  5. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  6. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  7. 75 FR 62406 - Plan To Develop a Genetic Testing Registry at the National Institutes of Health; Public Meeting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-08

    ... 301-496-9839; or via postal service to Cathy Fomous, Ph.D., Office of Biotechnology Activities... meeting agenda and public comments, please contact Cathy Fomous, Ph.D., NIH Office of Biotechnology... Biotechnology Information (NCBI), part of the National Library of Medicine at NIH, is responsible for...

  8. When genetics meets epigenetics: deciphering the mechanisms controlling inter-individual variation in immune responses to infection.

    PubMed

    Pacis, Alain; Nédélec, Yohann; Barreiro, Luis B

    2014-08-01

    The response of host immune cells to microbial stimuli is dependent on robust and coordinated gene expression programs involving the transcription of thousands of genes. The dysregulation of such regulatory programs is likely to significantly contribute to the marked differences in susceptibility to infectious diseases observed among individuals and between human populations. Although the specific factors leading to a dysfunctional immune response to infection remain largely unknown, we are increasingly appreciating the importance of genetic variants in altering the expression levels of immune-related genes, possibly via epigenetic changes. This review describes how recent technological advances have profoundly contributed to our current understanding of the genetic architecture and the epigenetic rules controlling immune responses to infectious agents and how genetic and epigenetic data can be combined to unravel the mechanisms associated with host variation in transcriptional responses to infection.

  9. Mouse genetics meets molecular biology at Cold Spring Harbor. Mouse Molecular Genetics sponsored by the Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA, August 29-September 2, 1990.

    PubMed

    Wagner, E F

    1990-12-01

    As stated earlier, the digestion of roughly 100 short talks delivered within a few days and containing very condensed information is, even for experts, quite demanding. Sometimes one felt in danger of becoming "psyched out" by all the experiments described; perhaps smaller group discussions dealing with experiments that have not worked, as well as the elimination of redundancies in the presentations, would have added to the flavor of the meeting. But what is the "take home message" from the 1990 CSH Mouse Meeting? With all the described breakthroughs, has mouse molecular genetics and development arrived at a turning point? I am inclined to answer this question with a "yes" on the basis of the following considerations: The elegant studies of development in Drosophila and Caenorhabditis elegans were made possible by the power of genetics with the use of developmental mutations. These studies taught us that the sequential activation of a hierarchy of regulatory genes dictates the temporal and spatial patterns of expression of proteins that define cell phenotypes and the body plan, and thereby control development. With the identification of important regulatory genes responsible for many classical as well as experimentally induced mouse mutations, in conjunction with traditional transgenic studies and the power of deleting and altering genes via ES cell chimeras, the study of mouse development has now gained an important new dimension. It is feasible that the consequences of subtle but precise genetic changes, such as the modification of regulatory elements or DNA-binding domains, can be studied in the whole organism by use of ES cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Refined genetic mapping of autosomal dominant retinitis pigmentosa locus RP18 reduces the critical region to 2 cM between D1S442 and D1S2858 on chromosome 1q.

    PubMed

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

    1998-04-01

    Linkage analysis was performed on a large Danish family to refine the position of RP18, the locus for autosomal dominant retinitis pigmentosa, mapped previously between D1S534 and D1S305 in chromosome 1p13-q21. We genotyped the family members for five microsatellite-type DNA polymorphisms and mapped RP18 between D1S422 and D1S2858 to a region of less than 2 cM. No obvious candidate gene has yet been assigned to the chromosomal interval defined here.

  11. Inferring relationships between pairs of individuals from locus heterozygosities

    PubMed Central

    Presciuttini, Silvano; Toni, Chiara; Tempestini, Elena; Verdiani, Simonetta; Casarino, Lucia; Spinetti, Isabella; Stefano, Francesco De; Domenici, Ranieri; Bailey-Wilson, Joan E

    2002-01-01

    Background The traditional exact method for inferring relationships between individuals from genetic data is not easily applicable in all situations that may be encountered in several fields of applied genetics. This study describes an approach that gives affordable results and is easily applicable; it is based on the probabilities that two individuals share 0, 1 or both alleles at a locus identical by state. Results We show that these probabilities (zi) depend on locus heterozygosity (H), and are scarcely affected by variation of the distribution of allele frequencies. This allows us to obtain empirical curves relating zi's to H for a series of common relationships, so that the likelihood ratio of a pair of relationships between any two individuals, given their genotypes at a locus, is a function of a single parameter, H. Application to large samples of mother-child and full-sib pairs shows that the statistical power of this method to infer the correct relationship is not much lower than the exact method. Analysis of a large database of STR data proves that locus heterozygosity does not vary significantly among Caucasian populations, apart from special cases, so that the likelihood ratio of the more common relationships between pairs of individuals may be obtained by looking at tabulated zi values. Conclusions A simple method is provided, which may be used by any scientist with the help of a calculator or a spreadsheet to compute the likelihood ratios of common alternative relationships between pairs of individuals. PMID:12441003

  12. [Study on preferred retinal locus].

    PubMed

    Dai, Bing-Fa; Hu, Jian-Min; Xu, Duan-Lian

    2012-03-01

    Preferred retinal locus (PRL) is always found in the age-related macular degeneration and other macular damages in patients with low vision, and it is a very important anatomic position in patients with central vision impairment to achieve the rehabilitation. In recent years, the training of preferred retinal locus (PRL) has become a research hotspot of low vision rehabilitation, it can clearly improve functional vision and quality of life. The authors reviewed relevant literatures, and summarized the definition, position, characteristics, training and clinical implications of the PRL.

  13. Where Birt–Hogg–Dubé meets Cowden Syndrome: mirrored genetic defects in two cases of syndromic oncocytic tumours

    PubMed Central

    Pradella, Laura Maria; Lang, Martin; Kurelac, Ivana; Mariani, Elisa; Guerra, Flora; Zuntini, Roberta; Tallini, Giovanni; MacKay, Alan; Reis-Filho, Jorge S; Seri, Marco; Turchetti, Daniela; Gasparre, Giuseppe

    2013-01-01

    Birt–Hogg–Dubè (BHD) is an autosomal dominant syndrome characterised by skin fibrofolliculomas, lung cysts, spontaneous pneumothorax and renal cancer. The association of benign cutaneous lesions and increased cancer risk is also a feature of Cowden Syndrome (CS), an autosomal dominant disease caused by PTEN mutations. BHD and CS patients may develop oncocytomas, rare neoplasias that are phenotypically characterised by a prominent mitochondrial hyperplasia. We here describe the genetic analysis of a parotid and a thyroid oncocytoma, developed by a BHD and a CS patient, respectively. The BHD lesion was shown to maintain the wild-type allele of FLCN, while losing one PTEN allele. On the other hand, a double heterozygosity for the same two genes was found to be the only detectable tumorigenic hit in the CS oncocytoma. Both conditions occurred in a context of high chromosomal stability, as highlighted by comparative genomic hybridisation analysis. We conclude that, similarly to PTEN, FLCN may not always follow the classical Two Hits model of tumorigenesis and may hence belong to a class of non-canonical tumour suppressor genes. We hence introduce a role of PTEN/FLCN double heterozygosity in syndromic oncocytic tumorigenesis, suggesting this to be an alternative determinant to pathogenic mitochondrial DNA mutations, which are instead the genetic hallmark of sporadic oncocytic tumours. PMID:23386036

  14. [Application of VNTR D17S30 locus polymorphism in the paternity test].

    PubMed

    Feng, M; Feng, Z; Lu, Q; Zhang, Y; Yang, Y; Ji, Y; Chen, R

    1998-01-01

    A sensitive and rapid PCR-based technique was adopted to genotype the VNTR D17S30 locus. It was confirmed through the genetic analysis of 20 normal families that the inheritance of D17S30 locus coincides with Mendelian law as simple co-dominant. Retrospective analysis of 100 paternity cases demonstrated that D17S30 locus could be used in forensic paternity test in our country. The exclusion probability estimated from allele frequencies of D17S30 locus (74.04%) does not differ significantly from the observed rate of exclusion (80.00%) in these cases. In all excluded paternity cases there are two in which the exclusion evidence is solely provided by the D17S30 locus.

  15. Locus of Control and Delinquency.

    ERIC Educational Resources Information Center

    Parrott, C. A.; Strongman, K. T.

    1984-01-01

    Assessed delinquent and nondelinquent male adolescents (N=43) on locus of control and intellectual achievement responsibilty. Results supported a multidimensional model. There was no difference in expectancy of control for negative academic events between delinquents and nondelinquents. Birth order and delinquency were the most important…

  16. Locus of Control and Socialization.

    ERIC Educational Resources Information Center

    Raine, Adrian; And Others

    1982-01-01

    Predicted that an external locus of control would characterize undersocialization. Tested this hypothesis on a random sample of secondary school children (N=97). Scores from the Child Nowicki-Strickland Internal-External Scale were found to predict undersocialization in the expected direction. Suggested several possible interpretations of this…

  17. Molecular anthropology meets genetic medicine to treat blindness in the North African Jewish population: human gene therapy initiated in Israel.

    PubMed

    Banin, Eyal; Bandah-Rozenfeld, Dikla; Obolensky, Alexey; Cideciyan, Artur V; Aleman, Tomas S; Marks-Ohana, Devora; Sela, Malka; Boye, Sanford; Sumaroka, Alexander; Roman, Alejandro J; Schwartz, Sharon B; Hauswirth, William W; Jacobson, Samuel G; Hemo, Itzhak; Sharon, Dror

    2010-12-01

    The history of the North African Jewish community is ancient and complicated with a number of immigration waves and persecutions dramatically affecting its population size. A decade-long process in Israel of clinical-molecular screening of North African Jews with incurable autosomal recessive blindness led to the identification of a homozygous splicing mutation (c.95-2A > T; IVS2-2A > T) in RPE65, the gene encoding the isomerase that catalyzes a key step in the retinoid-visual cycle, in patients from 10 unrelated families. A total of 33 patients (four now deceased) had the severe childhood blindness known as Leber congenital amaurosis (LCA), making it the most common cause of retinal degeneration in this population. Haplotype analysis in seven of the patients revealed a shared homozygous region, indicating a population-specific founder mutation. The age of the RPE65 founder mutation was estimated to have emerged 100-230 (mean, 153) generations ago, suggesting it originated before the establishment of the Jewish community in North Africa. Individuals with this RPE65 mutation were characterized with retinal studies to determine if they were candidates for gene replacement, the recent and only therapy to date for this otherwise incurable blindness. The step from molecular anthropological studies to application of genetic medicine was then taken, and a representative of this patient subgroup was treated with subretinal rAAV2-RPE65 gene therapy. An increase in vision was present in the treated area as early as 15 days after the intervention. This process of genetically analyzing affected isolated populations as a screen for gene-based therapy suggests a new paradigm for disease diagnosis and treatment.

  18. Locus-specific view of flax domestication history

    PubMed Central

    Fu, Yong-Bi; Diederichsen, Axel; Allaby, Robin G

    2012-01-01

    Crop domestication has been inferred genetically from neutral markers and increasingly from specific domestication-associated loci. However, some crops are utilized for multiple purposes that may or may not be reflected in a single domestication-associated locus. One such example is cultivated flax (Linum usitatissimum L.), the earliest oil and fiber crop, for which domestication history remains poorly understood. Oil composition of cultivated flax and pale flax (L. bienne Mill.) indicates that the sad2 locus is a candidate domestication locus associated with increased unsaturated fatty acid production in cultivated flax. A phylogenetic analysis of the sad2 locus in 43 pale and 70 cultivated flax accessions established a complex domestication history for flax that has not been observed previously. The analysis supports an early, independent domestication of a primitive flax lineage, in which the loss of seed dispersal through capsular indehiscence was not established, but increased oil content was likely occurred. A subsequent flax domestication process occurred that probably involved multiple domestications and includes lineages that contain oil, fiber, and winter varieties. In agreement with previous studies, oil rather than fiber varieties occupy basal phylogenetic positions. The data support multiple paths of flax domestication for oil-associated traits before selection of the other domestication-associated traits of seed dispersal loss and fiber production. The sad2 locus is less revealing about the origin of winter tolerance. In this case, a single domestication-associated locus is informative about the history of domesticated forms with the associated trait while partially informative on forms less associated with the trait. PMID:22408732

  19. Genomic characterization of the Atlantic cod sex-locus

    PubMed Central

    Star, Bastiaan; Tørresen, Ole K.; Nederbragt, Alexander J.; Jakobsen, Kjetill S.; Pampoulie, Christophe; Jentoft, Sissel

    2016-01-01

    A variety of sex determination mechanisms can be observed in evolutionary divergent teleosts. Sex determination is genetic in Atlantic cod (Gadus morhua), however the genomic location or size of its sex-locus is unknown. Here, we characterize the sex-locus of Atlantic cod using whole genome sequence (WGS) data of 227 wild-caught specimens. Analyzing more than 55 million polymorphic loci, we identify 166 loci that are associated with sex. These loci are located in six distinct regions on five different linkage groups (LG) in the genome. The largest of these regions, an approximately 55 Kb region on LG11, contains the majority of genotypes that segregate closely according to a XX-XY system. Genotypes in this region can be used genetically determine sex, whereas those in the other regions are inconsistently sex-linked. The identified region on LG11 and its surrounding genes have no clear sequence homology with genes or regulatory elements associated with sex-determination or differentiation in other species. The functionality of this sex-locus therefore remains unknown. The WGS strategy used here proved adequate for detecting the small regions associated with sex in this species. Our results highlight the evolutionary flexibility in genomic architecture underlying teleost sex-determination and allow practical applications to genetically sex Atlantic cod. PMID:27499266

  20. Exploring Genetic Diversity in Plants Using High-Throughput Sequencing Techniques

    PubMed Central

    Onda, Yoshihiko; Mochida, Keiichi

    2016-01-01

    Food security has emerged as an urgent concern because of the rising world population. To meet the food demands of the near future, it is required to improve the productivity of various crops, not just of staple food crops. The genetic diversity among plant populations in a given species allows the plants to adapt to various environmental conditions. Such diversity could therefore yield valuable traits that could overcome the food-security challenges. To explore genetic diversity comprehensively and to rapidly identify useful genes and/or allele, advanced high-throughput sequencing techniques, also called next-generation sequencing (NGS) technologies, have been developed. These provide practical solutions to the challenges in crop genomics. Here, we review various sources of genetic diversity in plants, newly developed genetic diversity-mining tools synergized with NGS techniques, and related genetic approaches such as quantitative trait locus analysis and genome-wide association study. PMID:27499684

  1. Exploring Genetic Diversity in Plants Using High-Throughput Sequencing Techniques.

    PubMed

    Onda, Yoshihiko; Mochida, Keiichi

    2016-08-01

    Food security has emerged as an urgent concern because of the rising world population. To meet the food demands of the near future, it is required to improve the productivity of various crops, not just of staple food crops. The genetic diversity among plant populations in a given species allows the plants to adapt to various environmental conditions. Such diversity could therefore yield valuable traits that could overcome the food-security challenges. To explore genetic diversity comprehensively and to rapidly identify useful genes and/or allele, advanced high-throughput sequencing techniques, also called next-generation sequencing (NGS) technologies, have been developed. These provide practical solutions to the challenges in crop genomics. Here, we review various sources of genetic diversity in plants, newly developed genetic diversity-mining tools synergized with NGS techniques, and related genetic approaches such as quantitative trait locus analysis and genome-wide association study.

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

    SciTech Connect

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

    1996-09-01

    Rieger syndrome is a genetically and phenotypically heterogeneous disorder typically characterized by malformations of the eyes, teeth, and umbilicus. The syndrome is inherited as an autosomal dominant trait and exhibits significant variable expressivity. One locus associated with this disorder has been mapped to 4q25. Using a large four-generation pedigree, we have identified a second locus for Rieger syndrome located on chromosome 13q14. 31 refs., 1 fig., 3 tabs.

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

    PubMed

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

    2012-01-01

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

  4. Locus of Control and Status Attainment.

    ERIC Educational Resources Information Center

    Bensman, Miriam Roza; Haller, Archibald O.

    Utilizing data derived from 277 rural, male respondents initially enrolled in Lenawee County, Michigan high schools, the Rotter's Internal-External Locus of Control Scale was employed to test the hypothesis that locus of control will have interactive rather than additive effects on the process of status attainment. Locus of control was defined as…

  5. Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development.

    PubMed

    Sovio, Ulla; Mook-Kanamori, Dennis O; Warrington, Nicole M; Lawrence, Robert; Briollais, Laurent; Palmer, Colin N A; Cecil, Joanne; Sandling, Johanna K; Syvänen, Ann-Christine; Kaakinen, Marika; Beilin, Lawrie J; Millwood, Iona Y; Bennett, Amanda J; Laitinen, Jaana; Pouta, Anneli; Molitor, John; Davey Smith, George; Ben-Shlomo, Yoav; Jaddoe, Vincent W V; Palmer, Lyle J; Pennell, Craig E; Cole, Tim J; McCarthy, Mark I; Järvelin, Marjo-Riitta; Timpson, Nicholas J

    2011-02-01

    An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p = 10(-20)) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p = 10(-23)). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06), p = 0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p = 0.01), and earlier AR (-4.72% (-5.81, -3.63), p = 10(-17)), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk.

  6. Geographic distribution of haplotype diversity at the bovine casein locus

    PubMed Central

    Jann, Oliver C; Ibeagha-Awemu, Eveline M; Özbeyaz, Ceyhan; Zaragoza, Pilar; Williams, John L; Ajmone-Marsan, Paolo; Lenstra, Johannes A; Moazami-Goudarzi, Katy; Erhardt, Georg

    2004-01-01

    The genetic diversity of the casein locus in cattle was studied on the basis of haplotype analysis. Consideration of recently described genetic variants of the casein genes which to date have not been the subject of diversity studies, allowed the identification of new haplotypes. Genotyping of 30 cattle breeds from four continents revealed a geographically associated distribution of haplotypes, mainly defined by frequencies of alleles at CSN1S1 and CSN3. The genetic diversity within taurine breeds in Europe was found to decrease significantly from the south to the north and from the east to the west. Such geographic patterns of cattle genetic variation at the casein locus may be a result of the domestication process of modern cattle as well as geographically differentiated natural or artificial selection. The comparison of African Bos taurus and Bos indicus breeds allowed the identification of several Bos indicus specific haplotypes (CSN1S1*C-CSN2*A2-CSN3*AI/CSN3*H) that are not found in pure taurine breeds. The occurrence of such haplotypes in southern European breeds also suggests that an introgression of indicine genes into taurine breeds could have contributed to the distribution of the genetic variation observed. PMID:15040901

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

    SciTech Connect

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

    1993-01-01

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

  8. Fine mapping and genetic association analysis of Net2, the causative D-genome locus of low temperature-induced hybrid necrosis in interspecific crosses between tetraploid wheat and Aegilops tauschii.

    PubMed

    Sakaguchi, Kouhei; Nishijima, Ryo; Iehisa, Julio Cesar Masaru; Takumi, Shigeo

    2016-10-01

    Hybrid necrosis has been observed in many interspecific hybrids from crosses between tetraploid wheat and the wheat D-genome donor Aegilops tauschii. Type II necrosis is a kind of hybrid incompatibility that is specifically characterized by low-temperature induction and growth suppression. Two complementary genes, Net1 on the AB genome and Net2 on the D genome, putatively control type II necrosis in ABD triploids and synthetic hexaploid wheat. Toward map-based cloning of Net2, a fine map around the Net2 region on 2DS was constructed in this study. Using the draft genome sequence of Ae. tauschii and the physical map of the barley genome, the Net2 locus was mapped within a 0.6 cM interval between two closely linked markers. Although local chromosomal rearrangements were observed in the Net2-corresponding region between the barley/Brachypodium and Ae. tauschii genomes, the two closely linked markers were significantly associated with type II necrosis in Ae. tauschii. These results suggest that these markers will aid efficient selection of Net2 non-carrier individuals from the Ae. tauschii population and intraspecific progeny, and could help with introgression of agriculturally important genes from Ae. tauschii to common wheat.

  9. Molecular Epidemiology of sil Locus in Clinical Streptococcus pyogenes Strains

    PubMed Central

    Plainvert, Céline; Dinis, Márcia; Ravins, Miriam; Hanski, Emanuel; Touak, Gérald; Dmytruk, Nicolas; Fouet, Agnès

    2014-01-01

    Streptococcus pyogenes (group A Streptococcus [GAS]) causes a wide variety of diseases, ranging from mild noninvasive to severe invasive infections. Mutations in regulatory components have been implicated in the switch from colonization to invasive phenotypes. The inactivation of the sil locus, composed of six genes encoding a quorum-sensing complex, gives rise to a highly invasive strain. However, studies conducted on limited collections of GAS strains suggested that sil prevalence is around 15%; furthermore, whereas a correlation between the presence of sil and the genetic background was suggested, no link between the presence of a functional sil locus and the invasive status was assessed. We established a collection of 637 nonredundant strains covering all emm genotypes present in France and of known clinical history; 68%, 22%, and 10% were from invasive infections, noninvasive infections, and asymptomatic carriage, respectively. Among the 637 strains, 206 were sil positive. The prevalence of the sil locus varied according to the emm genotype, being present in >85% of the emm4, emm18, emm32, emm60, emm87, and emm90 strains and absent from all emm1, emm28, and emm89 strains. A random selection based on 2009 French epidemiological data indicated that 16% of GAS strains are sil positive. Moreover, due to mutations leading to truncated proteins, only 9% of GAS strains harbor a predicted functional sil system. No correlation was observed between the presence or absence of a functional sil locus and the strain invasiveness status. PMID:24671796

  10. The Locus of Career Vitality. ASHE 1983 Annual Meeting Paper.

    ERIC Educational Resources Information Center

    Toombs, William

    The context for considering faculty career vitality is addressed. It is suggested that the unit of study should be individual, and that both internal and external influences should be considered. A contrasting view is that the institution should be the unit of study. A Pennsylvania State University study revealed that faculty career decisions were…

  11. 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.

  12. True hermaphroditism in a 46, XY individual, caused by a postzygotic somatic point mutation in the male gonadal sex-determining locus (SRY): Molecular genetics and histological findings in a sporadic case

    SciTech Connect

    Braun, A.; Kammerer, S.; Cleve, H.; Loehrs, U.; Schwarz, H.P.; Kuhnle, U. )

    1993-03-01

    Recently, the gene for the determination of maleness has been identified in the sex-determining region on the short arm of the Y chromosome (SRY) between the Y-chromosomal pseudoautosomal boundary (PABY) and the ZFY gene locus. Experiments with transgenic mice confirmed that SRY is a part of the testis-determining factor (TDF). The authors describe a sporadic case of a patient with intersexual genitalia and the histological finding of ovotestes in the gonad, which resembles the mixed type of gonadal tissue without primordial follicle structures. The karyotype of the patient was 46,XY. By PCR amplification, they tested for the presence of SRY by using DNA obtained from histological gonadal slices. The SRY products of both DNA preparations were further analyzed by direct sequencing. All three parts of the sex-determining region of the Y chromosome could be amplified from leukocytic DNA. The patient's and the father's SRY sequences were identical with the published sequence. In the SRY PCR product of gonadal DNA, the wild-type and two point mutations were present in the patient's sequence, simulating a heterozygous state of a Y-chromosomal gene: one of the mutations was silent, while the other encoded for a nonconservative amino acid substitution from leucine to histidine. Subcloning procedures showed that the two point mutations always occurred together. The origin of the patient's intersexuality is a postzygotic mutation of the SRY occurring in part of the gonadal tissue. This event caused the loss of the testis-determining function in affected cells. 37 refs., 6 figs.

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

    PubMed

    Chen, Yingnan; Wang, Tiantian; Fang, Lecheng; Li, Xiaoping; Yin, Tongming

    2016-01-01

    In this study, we constructed high-density genetic maps of Salix suchowensis and mapped the gender locus with an F1 pedigree. Genetic maps were separately constructed for the maternal and paternal parents by using amplified fragment length polymorphism (AFLP) markers and the pseudo-testcross strategy. The maternal map consisted of 20 linkage groups that spanned a genetic distance of 2333.3 cM; whereas the paternal map contained 21 linkage groups that covered 2260 cM. Based on the established genetic maps, it was found that the gender of willow was determined by a single locus on linkage group LG_03, and the female was the heterogametic gender. Aligned with mapped SSR markers, linkage group LG_03 was found to be associated with chromosome XV in willow. It is noteworthy that marker density in the vicinity of the gender locus was significantly higher than that expected by chance alone, which indicates severe recombination suppression around the gender locus. In conclusion, this study confirmed the findings on the single-locus sex determination and female heterogamety in willow. It also provided additional evidence that validated the previous studies, which found that different autosomes evolved into sex chromosomes between the sister genera of Salix (willow) and Populus (poplar).

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

    PubMed Central

    Fang, Lecheng; Li, Xiaoping; Yin, Tongming

    2016-01-01

    In this study, we constructed high-density genetic maps of Salix suchowensis and mapped the gender locus with an F1 pedigree. Genetic maps were separately constructed for the maternal and paternal parents by using amplified fragment length polymorphism (AFLP) markers and the pseudo-testcross strategy. The maternal map consisted of 20 linkage groups that spanned a genetic distance of 2333.3 cM; whereas the paternal map contained 21 linkage groups that covered 2260 cM. Based on the established genetic maps, it was found that the gender of willow was determined by a single locus on linkage group LG_03, and the female was the heterogametic gender. Aligned with mapped SSR markers, linkage group LG_03 was found to be associated with chromosome XV in willow. It is noteworthy that marker density in the vicinity of the gender locus was significantly higher than that expected by chance alone, which indicates severe recombination suppression around the gender locus. In conclusion, this study confirmed the findings on the single-locus sex determination and female heterogamety in willow. It also provided additional evidence that validated the previous studies, which found that different autosomes evolved into sex chromosomes between the sister genera of Salix (willow) and Populus (poplar). PMID:26828940

  15. Adaptation of maize to temperate climates: mid-density genome-wide association genetics and diversity patterns reveal key genomic regions, with a major contribution of the Vgt2 (ZCN8) locus.

    PubMed

    Bouchet, Sophie; Servin, Bertrand; Bertin, Pascal; Madur, Delphine; Combes, Valérie; Dumas, Fabrice; Brunel, Dominique; Laborde, Jacques; Charcosset, Alain; Nicolas, Stéphane

    2013-01-01

    The migration of maize from tropical to temperate climates was accompanied by a dramatic evolution in flowering time. To gain insight into the genetic architecture of this adaptive trait, we conducted a 50K SNP-based genome-wide association and diversity investigation on a panel of tropical and temperate American and European representatives. Eighteen genomic regions were associated with flowering time. The number of early alleles cumulated along these regions was highly correlated with flowering time. Polymorphism in the vicinity of the ZCN8 gene, which is the closest maize homologue to Arabidopsis major flowering time (FT) gene, had the strongest effect. This polymorphism is in the vicinity of the causal factor of Vgt2 QTL. Diversity was lower, whereas differentiation and LD were higher for associated loci compared to the rest of the genome, which is consistent with selection acting on flowering time during maize migration. Selection tests also revealed supplementary loci that were highly differentiated among groups and not associated with flowering time in our panel, whereas they were in other linkage-based studies. This suggests that allele fixation led to a lack of statistical power when structure and relatedness were taken into account in a linear mixed model. Complementary designs and analysis methods are necessary to unravel the architecture of complex traits. Based on linkage disequilibrium (LD) estimates corrected for population structure, we concluded that the number of SNPs genotyped should be at least doubled to capture all QTLs contributing to the genetic architecture of polygenic traits in this panel. These results show that maize flowering time is controlled by numerous QTLs of small additive effect and that strong polygenic selection occurred under cool climatic conditions. They should contribute to more efficient genomic predictions of flowering time and facilitate the dissemination of diverse maize genetic resources under a wide range of

  16. Adaptation of Maize to Temperate Climates: Mid-Density Genome-Wide Association Genetics and Diversity Patterns Reveal Key Genomic Regions, with a Major Contribution of the Vgt2 (ZCN8) Locus

    PubMed Central

    Bouchet, Sophie; Servin, Bertrand; Bertin, Pascal; Madur, Delphine; Combes, Valérie; Dumas, Fabrice; Brunel, Dominique; Laborde, Jacques; Charcosset, Alain; Nicolas, Stéphane

    2013-01-01

    The migration of maize from tropical to temperate climates was accompanied by a dramatic evolution in flowering time. To gain insight into the genetic architecture of this adaptive trait, we conducted a 50K SNP-based genome-wide association and diversity investigation on a panel of tropical and temperate American and European representatives. Eighteen genomic regions were associated with flowering time. The number of early alleles cumulated along these regions was highly correlated with flowering time. Polymorphism in the vicinity of the ZCN8 gene, which is the closest maize homologue to Arabidopsis major flowering time (FT) gene, had the strongest effect. This polymorphism is in the vicinity of the causal factor of Vgt2 QTL. Diversity was lower, whereas differentiation and LD were higher for associated loci compared to the rest of the genome, which is consistent with selection acting on flowering time during maize migration. Selection tests also revealed supplementary loci that were highly differentiated among groups and not associated with flowering time in our panel, whereas they were in other linkage-based studies. This suggests that allele fixation led to a lack of statistical power when structure and relatedness were taken into account in a linear mixed model. Complementary designs and analysis methods are necessary to unravel the architecture of complex traits. Based on linkage disequilibrium (LD) estimates corrected for population structure, we concluded that the number of SNPs genotyped should be at least doubled to capture all QTLs contributing to the genetic architecture of polygenic traits in this panel. These results show that maize flowering time is controlled by numerous QTLs of small additive effect and that strong polygenic selection occurred under cool climatic conditions. They should contribute to more efficient genomic predictions of flowering time and facilitate the dissemination of diverse maize genetic resources under a wide range of

  17. Pleiotropic locus for emotion recognition and amygdala volume identified using univariate and bivariate linkage

    PubMed Central

    Knowles, Emma E. M.; McKay, D. Reese; Kent, Jack W.; Sprooten, Emma; Carless, Melanie A.; Curran, Joanne E.; de Almeida, Marcio A. A.; Dyer, Thomas D.; Göring, Harald H. H.; Olvera, Rene; Duggirala, Ravi; Fox, Peter; Almasy, Laura; Blangero, John; Glahn, David. C.

    2014-01-01

    The role of the amygdala in emotion recognition is well established and separately each trait has been shown to be highly heritable, but the potential role of common genetic influences on both traits has not been explored. Here we present an investigation of the pleiotropic influences of amygdala and emotion recognition in a sample of randomly selected, extended pedigrees (N = 858). Using a combination of univariate and bivariate linkage we found a pleiotropic region for amygdala and emotion recognition on 4q26 (LOD = 4.34). Association analysis conducted in the region underlying the bivariate linkage peak revealed a variant meeting the corrected significance level (pBonferroni = 5.01×10−05) within an intron of PDE5A (rs2622497, Χ2 =16.67, p = 4.4×10−05) as being jointly influential on both traits. PDE5A has been implicated previously in recognition-memory deficits and is expressed in subcortical structures that are thought to underlie memory ability including the amygdala. The present paper extends our understanding of the shared etiology between amygdala and emotion recognition by showing that the overlap between the two traits is due, at least in part, to common genetic influences. Moreover, the present paper identifies a pleiotropic locus for the two traits and an associated variant, which localizes the genetic signal even more precisely. These results, when taken in the context of previous research, highlight the potential utility of PDE5-inhibitors for ameliorating emotion-recognition deficits in populations including, but not exclusively, those individuals suffering from mental or neurodegenerative illness. PMID:25322361

  18. 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.

  19. Hitch-hiking to a locus under balancing selection: high sequence diversity and low population subdivision at the S-locus genomic region in Arabidopsis halleri.

    PubMed

    Ruggiero, Maria Valeria; Jacquemin, Bertrand; Castric, Vincent; Vekemans, Xavier

    2008-02-01

    Hitch-hiking to a site under balancing selection is expected to produce a local increase in nucleotide polymorphism and a decrease in population differentiation compared with the background genomic level, but empirical evidence supporting these predictions is scarce. We surveyed molecular diversity at four genes flanking the region controlling self-incompatibility (the S-locus) in samples from six populations of the herbaceous plant Arabidopsis halleri, and compared their polymorphism with sequences from five control genes unlinked to the S-locus. As a preliminary verification, the S-locus flanking genes were shown to co-segregate with SRK, the gene involved in the self-incompatibility reaction at the pistil level. In agreement with theory, our results demonstrated a significant peak of nucleotide diversity around the S-locus as well as a significant decrease in population genetic structure in the S-locus region compared with both control genes and a set of seven unlinked microsatellite markers. This is consistent with the theoretical expectation that balancing selection is increasing the effective migration rate in subdivided populations. Although only four S-locus flanking genes were investigated, our results suggest that these two signatures of the hitch-hiking effect are localized in a very narrow genomic region.

  20. A quantitative trait locus for recognition of foreign eggs in the host of a brood parasite.

    PubMed

    Martín-Gálvez, D; Soler, J J; Martínez, J G; Krupa, A P; Richard, M; Soler, M; Møller, A P; Burke, T

    2006-03-01

    Avian brood parasites reduce the reproductive output of their hosts and thereby select for defence mechanisms such as ejection of parasitic eggs. Such defence mechanisms simultaneously select for counter-defences in brood parasites, causing a coevolutionary arms race. Although coevolutionary models assume that defences and counter-defences are genetically influenced, this has never been demonstrated for brood parasites. Here, we give strong evidence for genetic differences between ejector and nonejectors, which could allow the study of such host defence at the genetic level, as well as studies of maintenance of genetic variation in defences. Briefly, we found that magpies, that are the main host of the great spotted cuckoo in Europe, have alleles of one microsatellite locus (Ase64) that segregate between accepters and rejecters of experimental parasitic eggs. Furthermore, differences in ejection rate among host populations exploited by the brood parasite covaried significantly with the genetic distance for this locus.

  1. 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…

  2. Scrutinizing the FTO locus: compelling evidence for a complex, long-range regulatory context.

    PubMed

    Rask-Andersen, Mathias; Almén, Markus Sällman; Schiöth, Helgi B

    2015-11-01

    Single nucleotide polymorphisms (SNPs) within a genetic region including the first two introns of the gene encoding FTO have consistently been shown to be the strongest genetic factors influencing body mass index (BMI). However, this same also contains several regulatory DNA elements that affect the expression of IRX3 and IRX5, which respectively, are located approximately 500 kb and 1.2 Mbp downstream from the BMI-associated FTO locus. Through these affected regulatory elements, genetic variation at the FTO locus influences adipocyte development leading to decreased thermogenesis and increased lipid storage. These findings provide a genomic model for the functional implications of genetic variations at this locus, and also demonstrate the importance of accounting for chromatin-chromatin interactions when constructing hypotheses for the mechanisms of trait and disease-associated common genetic variants. Several consortia have generated genome-wide datasets describing different aspects of chromatin biology which can be utilized to predict functionality and propose biologically relevant descriptions of specific DNA regions. Here, we review some of the publically available data resources on genome function and organization that can be used to gain an overview of genetic regions of interest and to generate testable hypotheses for future studies. We use the BMI- and obesity-associated FTO locus as a subject as it poses an illustrative example on the value of these resources. We find that public databases strongly support long-range interactions between regulatory elements in the FTO locus with the IRXB cluster genes IRX3 and IRX5. Chromatin configuration capture data also support interactions across a large region stretching across from the RPGRIP1L gene, FTO and the IRXB gene cluster.

  3. Tomato mutants altered in bacterial disease resistance provide evidence for a new locus controlling pathogen recognition.

    PubMed Central

    Salmeron, J M; Barker, S J; Carland, F M; Mehta, A Y; Staskawicz, B J

    1994-01-01

    We have employed a genetic approach to study the resistance of tomato to the phytopathogenic bacterium Pseudomonas syringae pv tomato. Resistance to P. s. tomato depends upon expression of the Pto locus in tomato, which encodes a protein with similarity to serine/threonine protein kinases and recognizes pathogen strains expressing the avirulence gene avrPto. Eleven tomato mutants were isolated with altered resistance to P. s. tomato strains expressing avrPto. We identified mutations both in the Pto resistance locus and in a new locus designated Prf (for Pseudomonas resistance and fenthion sensitivity). The genetic approach allowed us to dissect the roles of these loci in signal transduction in response to pathogen attack. Lines carrying mutations in the Pto locus vary 200-fold in the degree to which they are susceptible to P. s. tomato strains expressing avrPto. The pto mutants retain sensitivity to the organophosphate insecticide fenthion; this trait segregates with Pto in genetic crosses. This result suggested that contrary to previous hypotheses, the Pto locus controls pathogen recognition but not fenthion sensitivity. Interestingly, mutations in the prf locus result in both complete susceptibility to P. s. tomato and insensitivity to fenthion, suggesting that Prf plays a role in tomato signaling in response to both pathogen elicitors and fenthion. Because pto and prf mutations do not alter recognition of Xanthomonas campestris strains expressing avrBsP, an avirulence gene recognized by all tested tomato cultivars, Prf does not play a general role in disease resistance but possibly functions specifically in resistance against P. s. tomato. Genetic analysis of F2 populations from crosses of pto and prf homozygotes indicated that the Pto and Prf loci are tightly linked. PMID:7911348

  4. MHC ANTIGEN-BINDING LOCUS SHOWS STRONG SIGNAL OF SELECTION AND HIGH VARIABILITY IN FUNDULUS HETEROCLITUS POPULATIONS

    EPA Science Inventory

    The major histocompatibility system provides a unique genetic locus in vertebrates to assess genetic diversity and to look for the effects of selecti.on on the immune system. Fish population studies using MHC are fairly new, and thus far they have focused on endangered population...

  5. Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee.

    PubMed

    Shappell, Scott B; Thomas, George V; Roberts, Richard L; Herbert, Ron; Ittmann, Michael M; Rubin, Mark A; Humphrey, Peter A; Sundberg, John P; Rozengurt, Nora; Barrios, Roberto; Ward, Jerrold M; Cardiff, Robert D

    2004-03-15

    The Pathological Classification of Prostate Lesions in Genetically Engineered Mice (GEM) is the result of a directive from the National Cancer Institute Mouse Models of Human Cancer Consortium Prostate Steering Committee to provide a hierarchical taxonomy of disorders of the mouse prostate to facilitate classification of existing and newly created mouse models and the translation to human prostate pathology. The proposed Bar Harbor Classification system is the culmination of three meetings and workshops attended by various members of the Prostate Pathology Committee of the Mouse Models of Human Cancer Consortium. A 2-day Pathology Workshop was held at The Jackson Laboratory in Bar Harbor, Maine, in October 2001, in which study sets of 93 slides from 22 GEM models were provided to individual panel members. The comparison of mouse and human prostate anatomy and disease demonstrates significant differences and considerable similarities that bear on the interpretation of the origin and natural history of their diseases. The recommended classification of mouse prostate pathology is hierarchical, and includes developmental, inflammatory, benign proliferative, and neoplastic disorders. Among the neoplastic disorders, preinvasive, microinvasive, and poorly differentiated neoplasms received the most attention. Specific criteria were recommended and will be discussed. Transitions between neoplastic states were of particular concern. Preinvasive neoplasias of the mouse prostate were recognized as focal, atypical, and progressive lesions. These lesions were designated as mouse prostatic intraepithelial neoplasia (mPIN). Some atypical lesions were identified in mouse models without evidence of progression to malignancy. The panel recommended that mPIN lesions not be given histological grades, but that mPIN be further classified as to the absence or presence of documented associated progression to invasive carcinoma. Criteria for recognizing microinvasion, for classification of

  6. Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii

    PubMed Central

    Meyer, Wieland; Aanensen, David M.; Boekhout, Teun; Cogliati, Massimo; Diaz, Mara R.; Esposto, Maria Carmela; Fisher, Matthew; Gilgado, Felix; Hagen, Ferry; Kaocharoen, Sirada; Litvintseva, Anastasia P.; Mitchell, Thomas G.; Simwami, Sitali P.; Trilles, Luciana; Viviani, Maria Anna; Kwon-Chung, June

    2010-01-01

    This communication describes the consensus multi-locus typing scheme established by the Cryptococcal Working Group I (Genotyping of Cryptococcus neoformans and C. gattii) of the International Society for Human and Animal Mycology (ISHAM) using seven unlinked genetic loci for global strain genotyping. These genetic loci include the housekeeping genes CAP59, GPD1, LAC1, PLB1, SOD1, URA5 and the IGS1 region. Allele and sequence type information are accessible at http://www.mlst.net/. PMID:19462334

  7. Genotyping of the Q locus in wheat by a simple PCR-RFLP method.

    PubMed

    Asakura, Nobuaki; Mori, Naoki; Nakamura, Chiharu; Ohtsuka, Ichiro

    2009-06-01

    The Q locus located on the long arm of chromosome 5A is a key factor in evolution and widespread cultivation of domesticated wheat. The Q locus pleiotropically affects many agronomically important traits including threshability, glume shape and tenacity, rachis fragility and others. Genotyping of the Q locus based on the complex traits is ambiguous due to their multi-genetic control through interactions with the Q locus. To determine the Q locus genotype of wheat accessions possessing A genome, we developed a method based on polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) analysis. The Q and q alleles were clearly distinguished by PCR-RFLP analysis at six conserved single nucleotide polymorphisms in common wheat and wild and cultivated einkorn, emmer and timopheevi wheat. The Q locus genotype of Triticum sinskajae, which is one of the einkorn wheat species and exhibits free-threshing trait, was determined to be qq as expected. This simple PCR-RLFP-based genotyping method should serve as a useful tool in studying the origin of Q and thus wheat evolution after domestication and the following widespread cultivation.

  8. A strabismus susceptibility locus on chromosome 7p

    PubMed Central

    Parikh, Vaishali; Shugart, Yin Yao; Doheny, Kimberly F.; Zhang, Jie; Li, Lan; Williams, John; Hayden, David; Craig, Brian; Capo, Hilda; Chamblee, Denise; Chen, Cathy; Collins, Mary; Dankner, Stuart; Fiergang, Dean; Guyton, David; Hunter, David; Hutcheon, Marcia; Keys, Marshall; Morrison, Nancy; Munoz, Michelle; Parks, Marshall; Plotsky, David; Protzko, Eugene; Repka, Michael X.; Sarubbi, Maria; Schnall, Bruce; Siatkowski, R. Michael; Traboulsi, Elias; Waeltermann, Joanne; Nathans, Jeremy

    2003-01-01

    Strabismus has been known to have a significant genetic component, but the mode of inheritance and the identity of the relevant genes have been enigmatic. This paper reports linkage analysis of nonsyndromic strabismus. The principal results of this study are: (i) the demonstrated feasibility of identifying and recruiting large families in which multiple members have (or had) strabismus; (ii) the linkage in one large family of a presumptive strabismus susceptibility locus to 7p22.1 with a multipoint logarithm of odds score of 4.51 under a model of recessive inheritance; and (iii) the failure to observe significant linkage to 7p in six other multiplex families, consistent with genetic heterogeneity among families. These findings suggest that it will be possible to localize and ultimately identify strabismus susceptibility genes by linkage analysis and mutation screening of candidate genes. PMID:14519848

  9. Mox: a novel modifier of the tomato Xa locus.

    PubMed

    Peterson, P W; Yoder, J I

    1995-01-01

    We have isolated a novel mutation that caused variegated leaf color in a tomato plant which had multiple maize Ac transposable elements and the tomato Xa allele. Xa is a previously characterized semi-dominant mutation that causes tomato leaves to be bright yellow when heterozygous (Xa/xa+). The mutation responsible for the new phenotype was named Mox (Modifier of Xa). The Mox mutation modified the Xa/xa+ yellow leaf phenotype in two ways: it compensated for the Xa allele resulting in a plant with a wildtype green color, and it caused somatic variegation which appeared as white and yellow sectors on the green background. Somatic variegation was visible only if the plant contained both the Mox and Xa loci. Genetic studies indicated that the Mox locus was linked in repulsion to Xa and that the Mox locus was genetically transmitted at a reduced frequency through the male gamete. Molecular characterization of the Ac elements in lines segregating for Mox identified an Ac insertion that appeared to cosegregate with Mox variegation. We propose a model in which the Mox mutation consists of a duplication of the xa+ allele and subsequent Ac-induced breakage of the duplicated region causes variegation.

  10. 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.

  11. RefSeq and LocusLink: NCBI gene-centered resources.

    PubMed

    Pruitt, K D; Maglott, D R

    2001-01-01

    Thousands of genes have been painstakingly identified and characterized a few genes at a time. Many thousands more are being predicted by large scale cDNA and genomic sequencing projects, with levels of evidence ranging from supporting mRNA sequence and comparative genomics to computing ab initio models. This, coupled with the burgeoning scientific literature, makes it critical to have a comprehensive directory for genes and reference sequences for key genomes. The NCBI provides two resources, LocusLink and RefSeq, to meet these needs. LocusLink organizes information around genes to generate a central hub for accessing gene-specific information for fruit fly, human, mouse, rat and zebrafish. RefSeq provides reference sequence standards for genomes, transcripts and proteins; human, mouse and rat mRNA RefSeqs, and their corresponding proteins, are discussed here. Together, RefSeq and LocusLink provide a non-redundant view of genes and other loci to support research on genes and gene families, variation, gene expression and genome annotation. Additional information about LocusLink and RefSeq is available at http://www.ncbi.nlm.nih.gov/LocusLink/.

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

    PubMed Central

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

    2006-01-01

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

  13. 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

  14. Linkage disequilibrium at the APA insecticidal seed protein locus of common bean (Phaseolus vulgaris L.)

    PubMed Central

    2010-01-01

    Background An interesting seed protein family with a role in preventing insect herbivory is the multi-gene, APA family encoding the α-amylase inhibitor, phytohemagglutinin and arcelin proteins of common bean (Phaseolus vulgaris). Variability for this gene family exists and has been exploited to breed for insect resistance. For example, the arcelin locus has been successfully transferred from wild to cultivated common bean genotypes to provide resistance against the bruchid species Zabrotes subfasciatus although the process has been hampered by a lack of genetic tools for and understanding about the locus. In this study, we analyzed linkage disequilibrium (LD) between microsatellite markers at the APA locus and bruchid resistance in a germplasm survey of 105 resistant and susceptible genotypes and compared this with LD in other parts of the genome. Results Microsatellite allele diversity was found to vary with each of the eight APA-linked markers analyzed, and two markers within the APA locus were found to be diagnostic for bruchid resistance or susceptibility and for the different arcelin alleles inherited from the wild accessions. Arc1 was found to provide higher levels of resistance than Arc5 and the markers in the APA locus were highly associated with resistance showing that introgression of this gene-family from wild beans provides resistance in cultivated beans. LD around the APA locus was found to be intermediate compared to other regions of the genome and the highest LD was found within the APA locus itself for example between the markers PV-atct001 and PV-ag004. Conclusions We found the APA locus to be an important genetic determinant of bruchid resistance and also found that LD existed mostly within the APA locus but not beyond it. Moderate LD was also found for some other regions of the genome perhaps related to domestication genes. The LD pattern may reflect the introgression of arcelin from the wild into the cultivated background through breeding. LD

  15. A Quantitative Trait Locus Influencing Anxiety in the Laboratory Rat

    PubMed Central

    Fernández-Teruel, Alberto; Escorihuela, Rosa M.; Gray, Jeffrey A.; Aguilar, Raúl; Gil, Luis; Giménez-Llort, Lydia; Tobeña, Adolf; Bhomra, Amarjit; Nicod, Alison; Mott, Richard; Driscoll, Peter; Dawson, Gerard R.; Flint, Jonathan

    2002-01-01

    A critical test for a gene that influences susceptibility to fear in animals is that it should have a consistent pattern of effects across a broad range of conditioned and unconditioned models of anxiety. Despite many years of research, definitive evidence that genetic effects operate in this way is lacking. The limited behavioral test regimes so far used in genetic mapping experiments and the lack of suitable multivariate methodologies have made it impossible to determine whether the quantitative trait loci (QTL) detected to date specifically influence fear-related traits. Here we report the first multivariate analysis to explore the genetic architecture of rodent behavior in a battery of animal models of anxiety. We have mapped QTLs in an F2 intercross of two rat strains, the Roman high and low avoidance rats, that have been selectively bred for differential response to fear. Multivariate analyses show that one locus, on rat chromosome 5, influences behavior in different models of anxiety. The QTL influences two-way active avoidance, conditioned fear, elevated plus maze, and open field activity but not acoustic startle response or defecation in a novel environment. The direction of effects of the QTL alleles and a coincidence between the behavioral profiles of anxiolytic drug and genetic action are consistent with the QTL containing at least one gene with a pleiotropic action on fear responses. As the neural basis of fear is conserved across species, we suggest that the QTL may have relevance to trait anxiety in humans. PMID:11932246

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

    PubMed Central

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

    1996-01-01

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

  17. Organization and Evolutionary Trajectory of the Mating Type (MAT) Locus in Dermatophyte and Dimorphic Fungal Pathogens▿ †

    PubMed Central

    Li, Wenjun; Metin, Banu; White, Theodore C.; Heitman, Joseph

    2010-01-01

    Sexual reproduction in fungi is governed by a specialized genomic region, the mating type (MAT) locus, whose gene identity, organization, and complexity are diverse. We identified the MAT locus of five dermatophyte fungal pathogens (Microsporum gypseum, Microsporum canis, Trichophyton equinum, Trichophyton rubrum, and Trichophyton tonsurans) and a dimorphic fungus, Paracoccidioides brasiliensis, and performed phylogenetic analyses. The identified MAT locus idiomorphs of M. gypseum control cell type identity in mating assays, and recombinant progeny were produced. Virulence tests in Galleria mellonella larvae suggest the two mating types of M. gypseum may have equivalent virulence. Synteny analysis revealed common features of the MAT locus shared among these five dermatophytes: namely, a small size (∼3 kb) and a novel gene arrangement. The SLA2, COX13, and APN2 genes, which flank the MAT locus in other Ascomycota are instead linked on one side of the dermatophyte MAT locus. In addition, the transcriptional orientations of the APN2 and COX13 genes are reversed compared to the dimorphic fungi Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii. A putative transposable element, pogo, was found to have inserted in the MAT1-2 idiomorph of one P. brasiliensis strain but not others. In conclusion, the evolution of the MAT locus of the dermatophytes and dimorphic fungi from the last common ancestor has been punctuated by both gene acquisition and expansion, and asymmetric gene loss. These studies further support a foundation to develop molecular and genetic tools for dermatophyte and dimorphic human fungal pathogens. PMID:19880755

  18. Role of a Putative Polysaccharide Locus in Bordetella Biofilm Development▿

    PubMed Central

    Parise, Gina; Mishra, Meenu; Itoh, Yoshikane; Romeo, Tony; Deora, Rajendar

    2007-01-01

    Bordetellae are gram-negative bacteria that colonize the respiratory tracts of animals and humans. We and others have recently shown that these bacteria are capable of living as sessile communities known as biofilms on a number of abiotic surfaces. During the biofilm mode of existence, bacteria produce one or more extracellular polymeric substances that function, in part, to hold the cells together and to a surface. There is little information on either the constituents of the biofilm matrix or the genetic basis of biofilm development by Bordetella spp. By utilizing immunoblot assays and by enzymatic hydrolysis using dispersin B (DspB), a glycosyl hydrolase that specifically cleaves the polysaccharide poly-β-1,6-N-acetyl-d-glucosamine (poly-β-1,6-GlcNAc), we provide evidence for the production of poly-β-1,6-GlcNAc by various Bordetella species (Bordetella bronchiseptica, B. pertussis, and B. parapertussis) and its role in their biofilm development. We have investigated the role of a Bordetella locus, here designated bpsABCD, in biofilm formation. The bps (Bordetella polysaccharide) locus is homologous to several bacterial loci that are required for the production of poly-β-1,6-GlcNAc and have been implicated in bacterial biofilm formation. By utilizing multiple microscopic techniques to analyze biofilm formation under both static and hydrodynamic conditions, we demonstrate that the bps locus, although not essential at the initial stages of biofilm formation, contributes to the stability and the maintenance of the complex architecture of Bordetella biofilms. PMID:17114249

  19. Major-locus contributions to variability of the craniofacial feature dystopia canthorum in Waardenburg syndrome.

    PubMed

    Reynolds, J E; Marazita, M L; Meyer, J M; Stevens, C A; Eaves, L J; Arnos, K S; Ploughman, L M; MacLean, C; Nance, W E; Diehl, S R

    1996-02-01

    We used segregation analysis to investigate the genetic basis of variation in dystopia canthorum, one of the key diagnostic features of Waardenburg syndrome type 1 (WS1). We sought to determine whether the W-index, a quantitative measure of this craniofacial feature, is influenced primarily either by allelic variation in the PAX3 disease gene or other major loci, by polygenic background effects, or by all of these potential sources of genetic variation. We studied both WS1-affected individuals and their WS1-unaffected relatives. After adjustment of the W-index for WS1 disease status, segregation analyses by the regression approach indicated major-locus control of this variation, although residual parent-offspring and sib-sib correlations are consistent with additional (possibly polygenic) effects. Separate analyses of WS1-affected and WS1-unaffected individuals suggest that epistatic interactions between disease alleles at the PAX3 WS1 locus and a second major locus influence variation in dystopia canthorum. Our approach should be applicable for assessing the genetic architecture of variation associated with other genetic diseases.

  20. Novel Locus FER Is Associated With Serum HMW Adiponectin Levels

    PubMed Central

    Qi, Lu; Menzaghi, Claudia; Salvemini, Lucia; De Bonis, Concetta; Trischitta, Vincenzo; Hu, Frank B.

    2011-01-01

    OBJECTIVE High molecular weight (HMW) adiponectin is a predominant isoform of circulating adiponectin and has been related to type 2 diabetes. Previous linkage studies suggest that different genetic components might be involved in determining HMW and total adiponectin levels. RESEARCH DESIGN AND METHODS We performed a genome-wide association study (GWAS) of serum HMW adiponectin levels in individuals of European ancestry drawn from the Nurses’ Health Study (NHS) (N = 1,591). The single nucleotide polymorphisms (SNPs) identified in the GWAS analysis were replicated in an independent cohort of Europeans (N = 626). We examined the associations of the identified variations with diabetes risk and metabolic syndrome. RESULTS We identified a novel locus near the FER gene (5q21) at a genome-wide significance level, best represented by SNP rs10447248 (P = 4.69 × 10−8). We also confirmed that variations near the adiponectin-encoding ADIPOQ locus (3q27) were related to serum HMW adiponectin levels. In addition, we found that FER SNP rs10447248 was related to HDL cholesterol levels (P = 0.009); ADIPOQ variation was associated with fasting glucose (P = 0.04), HDL cholesterol (P = 0.04), and a metabolic syndrome score (P = 0.002). CONCLUSIONS Our results suggest that different loci may be involved in regulation of circulating HMW adiponectin levels and provide novel insight into the mechanisms that affect HMW adiponectin homeostasis. PMID:21700879

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

    PubMed

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

    2007-06-01

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

  2. Drosophila histone locus bodies form by hierarchical recruitment of components

    PubMed Central

    White, Anne E.; Burch, Brandon D.; Yang, Xiao-cui; Gasdaska, Pamela Y.; Dominski, Zbigniew; Marzluff, William F.

    2011-01-01

    Nuclear bodies are protein- and RNA-containing structures that participate in a wide range of processes critical to genome function. Molecular self-organization is thought to drive nuclear body formation, but whether this occurs stochastically or via an ordered, hierarchical process is not fully understood. We addressed this question using RNAi and proteomic approaches in Drosophila melanogaster to identify and characterize novel components of the histone locus body (HLB), a nuclear body involved in the expression of replication-dependent histone genes. We identified the transcription elongation factor suppressor of Ty 6 (Spt6) and a homologue of mammalian nuclear protein of the ataxia telangiectasia–mutated locus that is encoded by the homeotic gene multisex combs (mxc) as novel HLB components. By combining genetic manipulation in both cell culture and embryos with cytological observations of Mxc, Spt6, and the known HLB components, FLICE-associated huge protein, Mute, U7 small nuclear ribonucleoprotein, and MPM-2 phosphoepitope, we demonstrated sequential recruitment and hierarchical dependency for localization of factors to HLBs during development, suggesting that ordered assembly can play a role in nuclear body formation. PMID:21576393

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

    PubMed

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

    2008-05-01

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

  4. 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.

  5. GENETIC DIVERSITY, PARENTAGE VERIFICATION AND GENETIC BOTTLENECKS EVALUATION IN IRANIAN TURKMEN HORSE BREED.

    PubMed

    Rahimi-Mianji, G; Nejati-Javaremi, A; Farhadi, A

    2015-09-01

    The present study was undertaken to genetically evaluate Turkmen horses for genetic diversity and to evaluate whether they have experienced any recent genetic bottlenecks. A total of 565 individuals from Turkmen horses were characterized for within breed diversity using 12 microsatellite markers. The estimated mean allelic diversity was (9.42 ± 1.78) per locus, with a total of 131 alleles in genotyped samples. A high level of genetic variability within this breed was observed in terms of high values of effective number of alleles (4.70 ± 1.36), observed heterozygosity (0.757 ± 0.19), expected Nei's heterozygosity (0.765 ± 0.13), and polymorphism information content (0.776 ± 0.17). The estimated cumulative probability of exclusion of wrongly named parents (PE) was high, with an average value of 99.96% that indicates the effectiveness of applied markers in resolving of parentage typing in Turkmen horse population. The paternity testing results did not show any misidentification and all selected animals were qualified based on genotypic information using a likelihood-based method. Low values of Wright's fixation index, F(IS) (0.012) indicated low levels of inbreeding. A significant heterozygote excess on the basis of different models, as revealed from Sign and Wilcoxon sign rank test suggested that Turkmen horse population is not in mutation-drift equilibrium. But, the Mode-shift indicator test showed a normal 'L' shaped distribution for allelic class and proportion of alleles, thus indicating the absence of bottleneck events in the recent past history of this breed. Further research work should be carrying out to clarify the cause of discrepancy observed forbottleneck results in this breed. In conclusion, despite unplanned breeding in Turkmen horse population, this breed still has sufficient genetic variability and could provide a valuable source of genetic material that may use for meeting the demands of future breeding programs.

  6. Molecular characterization of the mouse agouti locus.

    PubMed

    Bultman, S J; Michaud, E J; Woychik, R P

    1992-12-24

    The agouti (a) locus acts within the microenvironment of the hair follicle to regulate coat color pigmentation in the mouse. We have characterized a gene encoding a novel 131 amino acid protein that we propose is the one gene associated with the agouti locus. This gene is normally expressed in a manner consistent with a locus function, and, more importantly, its structure and expression are affected by a number of representative alleles in the agouti dominance hierarchy. In addition, we found that the pleiotropic effects associated with the lethal yellow (Ay) mutation, which include pronounced obesity, diabetes, and the development of neoplasms, are accompanied by deregulated overexpression of the agouti gene in numerous tissues of the adult animal.

  7. Pollen genetic markers for detection of mutagens in the environment

    SciTech Connect

    Nilan, R.A.; Rosichan, J.L.; Arenaz, P.; Hodgdon, A.L.; Kleinhofs, A.

    1980-01-01

    To utilize and exploit pollen for in situ mutagen monitoring, screening and toxicology, the range of genetic traits in pollen must be identified and analyzed. To be useful for the development of mutagen detection systems proteins should be: (1) activity stainable or immunologically identifiable in the pollen, (2) the products of one to three loci; and (3) gametophytic and nuclear in origin. Several proteins, including alcohol dehydrogenase in maize, which meet these criteria are discussed. The waxy locus in barley and maize which controls starch deposition for pollen screening and mutant detection. Thirty waxy mutant lines, induced by sodium azide and gamma-rays are characterized for spontaneous and induced reversion frequencies, allelism, karyotype, amylose content, and UDPglucose glucosyltransferase (waxy gene product) activity. Twelve mutant alleles are being mapped by recombinant frequencies.

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

    SciTech Connect

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

    1994-06-15

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

  9. CSGRqtl: A Comparative Quantitative Trait Locus Database for Saccharinae Grasses.

    PubMed

    Zhang, Dong; Paterson, Andrew H

    2017-01-01

    Conventional biparental quantitative trait locus (QTL) mapping has led to some successes in the identification of causal genes in many organisms. QTL likelihood intervals not only provide "prior information" for finer-resolution approaches such as GWAS but also provide better statistical power than GWAS to detect variants with low/rare frequency in a natural population. Here, we describe a new element of an ongoing effort to provide online resources to facilitate study and improvement of the important Saccharinae clade. The primary goal of this new resource is the anchoring of published QTLs for this clade to the Sorghum genome. Genetic map alignments translate a wealth of genomic information from sorghum to Saccharum spp., Miscanthus spp., and other taxa. In addition, genome alignments facilitate comparison of the Saccharinae QTL sets to those of other taxa that enjoy comparable resources, exemplified herein by rice.

  10. Multipoint mapping of the central core disease locus

    SciTech Connect

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

    1993-07-01

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

  11. Response to selection in finite locus models with non-additive effects.

    PubMed

    Esfandyari, Hadi; Henryon, Mark; Berg, Peer; Thomasen, Jorn Rind; Bijma, Piter; Sørensen, Anders Christian

    2017-01-12

    Under the finite-locus model in the absence of mutation, the additive genetic variation is expected to decrease when directional selection is acting on a population, according to quantitative-genetic theory. However, some theoretical studies of selection suggest that the level of additive variance can be sustained or even increased when non-additive genetic effects are present. We tested the hypothesis that finite-locus models with both additive and non-additive genetic effects maintain more additive genetic variance (V_A) and realize larger medium-to-long term genetic gains than models with only additive effects when the trait under selection is subject to truncation selection. Four genetic models that included additive, dominance, and additive-by-additive epistatic effects were simulated. The simulated genome for individuals consisted of 25 chromosomes, each with a length of 1M. One hundred bi-allelic QTL, four on each chromosome, were considered. In each generation, 100 sires and 100 dams were mated, producing five progeny per mating. The population was selected for a single trait (h(2)=0.1) for 100 discrete generations with selection on phenotype or BLUP-EBV. V_A decreased with directional truncation selection even in presence of non-additive genetic effects. Non-additive effects influenced long-term response to selection and among genetic models additive gene action had highest response to selection. In addition, in all genetic models, BLUP-EBV resulted in a greater fixation of favourable and unfavourable alleles and higher response than phenotypic selection. In conclusion, for the schemes we simulated, the presence of non-additive genetic effects had little effect in changes of additive variance and V_A decreased by directional selection.

  12. Locus Adh of Drosophila melanogaster under selection for delayed senescence

    SciTech Connect

    Khaustova, N.D.

    1995-05-01

    Dynamics of the Adh activity and frequencies of alleles Adh{sup F} and Adh{sup S} were analyzed under selection for delayed senescence. The experiments were performed on Drosophila melanogaster. Lines Adh{sup S}cn and Adh{sup F}vg and experimental populations cn` and vg`, selected for an increased duration of reproductive period (late oviposition) were used. Analysis of fertility, longevity, viability and resistance to starvation showed that selection for late oviposition resulted in delayed senescence of flies of the experimental populations. Genetic structure of population vg` changed considerably with regard to the Adh locus. This was confirmed by parameters of activity, thermostability, and electrophoretic mobility of the enzyme isolated from flies after 30 generations of selection. Analysis of frequencies of the Adh alleles showed that in both selected populations, which initially had different genetic composition, accumulated allele Adh{sup S}, which encodes the isozyme that is less active but more resistant to inactivation. Genetic mechanism of delayed senescence in Drosophila is assumed to involve selection at vitally important enzyme loci, including Adh. 18 refs., 2 tabs., 4 figs.

  13. Molecular cloning of a putative receptor protein kinase gene encoded at the self-incompatibility locus of Brassica oleracea

    SciTech Connect

    Stein, J.C.; Howlett, B.; Boyes, D.C.; Nasrallah, M.E.; Nasrallah, J.B. )

    1991-10-01

    Self-recognition between pollen and stigma during pollination in Brassica oleracea is genetically controlled by the multiallelic self-incompatibility locus (S). The authors describe the S receptor kinase (SRK) gene, a previously uncharacterized gene that residues at the S locus. The nucleotide sequences of genomic DNA and of cDNAs corresponding to SRK predict a putative transmembrane receptor having serine/threonine-specific protein kinase activity. Its extracellular domain exhibits striking homology to the secreted product of the S-locus genotypes are highly polymorphic and have apparently evolved in unison with genetically linked alleles of SLG. SRK directs the synthesis of several alternative transcripts, which potentially encode different protein products, and these transcripts were detected exclusively in reproductive organs. The identification of SRK may provide new perspectives into the signal transduction mechanism underlying pollen recognition.

  14. Molecular analysis of 36 mutations at the mouse pink-eyed dilution (p) locus.

    PubMed

    Johnson, D K; Stubbs, L J; Culiat, C T; Montgomery, C S; Russell, L B; Rinchik, E M

    1995-12-01

    Thirty-six radiation- or chemically induced homozygous-lethal mutations at the p locus in mouse chromosome 7 have been analyzed at 17 loci defined by molecular probes to determine the types of lesions, numbers of p-region markers deleted or rearranged, regions of overlap of deletion mutations, and genetic distances between loci. A linear deletion map of the [Myod1, Ldh3]-[Snrpn, Znf127] region has been constructed from the molecular analyses of the p-locus deletions. The utility of these deletions as tools for the isolation and characterization of the genes specifying the neurological, reproductive, and developmental phenotypes genetically mapped to this region will grow as more detailed molecular analyses continue.

  15. Genetics of Eosinophilic Esophagitis

    DTIC Science & Technology

    2011-03-01

    staining for major basic protein in esophageal tissue (arrowheads) in WT than IL21R-/- mice (A) is quantified morphometrically in (B). Quantitative PCR... morphometric analysis was used to measure IL21 receptor expression in patient esophageal biopsies. RESULTS: A number of genetic variants on chromosome 4q26-27...variants in the locus. Immunofluorescent microscopy and morphometric analysis demonstrate a marked increase in IL21 receptor- expressing cells within

  16. Genetics of Eosinophilic Esophagitis

    DTIC Science & Technology

    2012-03-01

    in esophageal tissue (arrowheads) in WT than IL21R-/- mice (A) is quantified morphometrically in (B). Quantitative PCR (C) for esophageal...microscopy and morphometric analysis was used to measure IL21 receptor expression in patient esophageal biopsies. RESULTS: A number of genetic variants...most highly associated variants in the locus. Immunofluorescent microscopy and morphometric analysis demonstrate a marked increase in IL21 receptor

  17. Dental Outpatients: Health Locus of Control Correlates.

    ERIC Educational Resources Information Center

    Ludenia, Krista; Donham, Greg W.

    1983-01-01

    Examined relationships among specific personality variables, the Multidimensional Health Locus of Control Scales, and criterion-based ratings by staff dentists with dental outpatients (N=101). Found a consistent relationship between the perception that health is maintained by engaging in health-related behaviors and individual difference measures…

  18. The Preconscious: Locus for Significant Written Compositions.

    ERIC Educational Resources Information Center

    Alley, Alvin D.

    1979-01-01

    The author suggests that the preconscious is the true locus of significant prose because of its greater amount of freedom to gather, compare, and rearrange ideas, and that the ultimate challenge to teachers of composition is to give freedom to their students' preconscious processes. (KC)

  19. Exercise Adherence and Locus of Control.

    ERIC Educational Resources Information Center

    Geshuri, Yosef; Glahn, Ronald

    In 1990, a study was conducted to investigate the relationship between students' locus of control and the extent to which they participated in a voluntary exercise program. First-time participants in the "Shape Up" program offered at the Porterville College Fitness Center during the summer and fall semesters of 1990 were identified through the…

  20. Intrahaplotype polymorphism at the Brassica S locus.

    PubMed Central

    Miege, C; Ruffio-Châble, V; Schierup, M H; Cabrillac, D; Dumas, C; Gaude, T; Cock, J M

    2001-01-01

    The S locus receptor kinase and the S locus glycoproteins are encoded by genes located at the S locus, which controls the self-incompatibility response in Brassica. In class II self-incompatibility haplotypes, S locus glycoproteins can be encoded by two different genes, SLGA and SLGB. In this study, we analyzed the sequences of these genes in several independently isolated plants, all of which carry the same S haplotype (S(2)). Two groups of S(2) haplotypes could be distinguished depending on whether SRK was associated with SLGA or SLGB. Surprisingly, SRK alleles from the two groups could be distinguished at the sequence level, suggesting that recombination rarely occurs between haplotypes of the two groups. An analysis of the distribution of polymorphisms along the S domain of SRK showed that hypervariable domains I and II tend to be conserved within haplotypes but to be highly variable between haplotypes. This is consistent with these domains playing a role in the determination of haplotype specificity. PMID:11606555

  1. Locus of Control, Social Class, and Learning.

    ERIC Educational Resources Information Center

    Vasquez, James A.

    The relationship between locus of control, social class, and learning processes were reviewed by analyzing: (1) externality as a function of socioeconomic status, i.e., the lower the status, the greater the degree of externality; (2) the impact of the early home environment on the child's learning and development; (3) classroom and teacher…

  2. Understanding & Teaching Genetics Using Analogies

    ERIC Educational Resources Information Center

    Woody, Scott; Himelblau, Ed

    2013-01-01

    We present a collection of analogies that are intended to help students better understand the foreign and often nuanced vocabulary of the genetics curriculum. Why is it called the "wild type"? What is the difference between a locus, a gene, and an allele? What is the functional (versus a rule-based) distinction between dominant and…

  3. Development and validation of a breeder-friendly KASPar marker for wheat leaf rust resistance locus Lr21

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Development and utilization of genetic markers play a pivotal role in marker assisted breeding of wheat cultivars with pyramids of disease resistance genes. The objective of this study is to develop a closed tube, gel-free assay for high throughput genotyping of leaf rust resistance locus Lr21. Poly...

  4. A Functional and Structural Analysis of the Sex Combs Reduced Locus of Drosophila Melanogaster

    PubMed Central

    Pattatucci, A. M.; Otteson, D. C.; Kaufman, T. C.

    1991-01-01

    We have undertaken a developmental genetic analysis of the homeotic gene Sex combs reduced (Scr) of Drosophila melanogaster by examining embryonic and adult phenotypes of mutations affecting Scr gene function. Molecular mapping of Scr breakpoint lesions has defined a segment of >70 kb of DNA necessary for proper Scr gene function. This region is split by the fushi tarazu (ftz) gene, with lesions affecting embryonic Scr function molecularly mapping to the region proximal (5') to ftz and those exhibiting polyphasic semilethality predominantly mapping distal (3') to ftz. Gain-of-function mutations are associated with genomic rearrangements and map throughout the Scr locus. Our analysis has revealed that the Scr locus encompasses genetic elements that are responsible for functions in both the embryonic and larval to adult periods of development. From these studies, we conclude that Scr is a complex genetic locus with an extensive regulatory region that directs functions required for normal head and thoracic development in both the embryo and the adult and that the regulation of Scr during these two periods is distinct. PMID:1743486

  5. Incorporating Single-Locus Tests into Haplotype Cladistic Analysis in Case-Control Studies

    PubMed Central

    Liu, Jianfeng; Papasian, Chris; Deng, Hong-Wen

    2007-01-01

    In case-control studies, genetic associations for complex diseases may be probed either with single-locus tests or with haplotype-based tests. Although there are different views on the relative merits and preferences of the two test strategies, haplotype-based analyses are generally believed to be more powerful to detect genes with modest effects. However, a main drawback of haplotype-based association tests is the large number of distinct haplotypes, which increases the degrees of freedom for corresponding test statistics and thus reduces the statistical power. To decrease the degrees of freedom and enhance the efficiency and power of haplotype analysis, we propose an improved haplotype clustering method that is based on the haplotype cladistic analysis developed by Durrant et al. In our method, we attempt to combine the strengths of single-locus analysis and haplotype-based analysis into one single test framework. Novel in our method is that we develop a more informative haplotype similarity measurement by using p-values obtained from single-locus association tests to construct a measure of weight, which to some extent incorporates the information of disease outcomes. The weights are then used in computation of similarity measures to construct distance metrics between haplotype pairs in haplotype cladistic analysis. To assess our proposed new method, we performed simulation analyses to compare the relative performances of (1) conventional haplotype-based analysis using original haplotype, (2) single-locus allele-based analysis, (3) original haplotype cladistic analysis (CLADHC) by Durrant et al., and (4) our weighted haplotype cladistic analysis method, under different scenarios. Our weighted cladistic analysis method shows an increased statistical power and robustness, compared with the methods of haplotype cladistic analysis, single-locus test, and the traditional haplotype-based analyses. The real data analyses also show that our proposed method has practical

  6. Evolution and ecology meet molecular genetics: adaptive phenotypic plasticity in two isolated Negev desert populations of Acacia raddiana at either end of a rainfall gradient

    PubMed Central

    Ward, David; Shrestha, Madan K.; Golan-Goldhirsh, Avi

    2012-01-01

    Background and Aims The ecological, evolutionary and genetic bases of population differentiation in a variable environment are often related to the selection pressures that plants experience. We compared differences in several growth- and defence-related traits in two isolated populations of Acacia raddiana trees from sites at either end of an extreme environmental gradient in the Negev desert. Methods We used random amplified polymorphic DNA (RAPD) to determine the molecular differences between populations. We grew plants under two levels of water, three levels of nutrients and three levels of herbivory to test for phenotypic plasticity and adaptive phenotypic plasticity. Key Results The RAPD analyses showed that these populations are highly genetically differentiated. Phenotypic plasticity in various morphological traits in A. raddiana was related to patterns of population genetic differentiation between the two study sites. Although we did not test for maternal effects in these long-lived trees, significant genotype × environment (G × E) interactions in some of these traits indicated that such plasticity may be adaptive. Conclusions The main selection pressure in this desert environment, perhaps unsurprisingly, is water. Increased water availability resulted in greater growth in the southern population, which normally receives far less rain than the northern population. Even under the conditions that we defined as low water and/or nutrients, the performance of the seedlings from the southern population was significantly better, perhaps reflecting selection for these traits. Consistent with previous studies of this genus, there was no evidence of trade-offs between physical and chemical defences and plant growth parameters in this study. Rather, there appeared to be positive correlations between plant size and defence parameters. The great variation in several traits in both populations may result in a diverse potential for responding to selection pressures in

  7. 75 FR 62549 - National Library of Medicine; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-12

    ... the following meeting of the Medical Genetics Working Group. ] The meeting will be open to the public... Genetics Working Group. Date: November 10, 2010. Time: 1 p.m. to 5 p.m. Agenda: Programmatic and policy needs and opportunities related to NCBI information resources in the medical genetics area....

  8. Locus of control and the fundamental dimensions of moods.

    PubMed

    Henson, H N; Chang, E C

    1998-06-01

    The present study examined the association between locus of control and positive and negative moods in 253 college students. Using the PANAS-X, designed by Watson and Clark, individuals scoring high on internal locus of control also scored higher across different dimensions of positive mood. Conversely, individuals scoring high on external locus of control had higher scores across different dimensions of negative mood.

  9. Self-Esteem, Locus of Control, and Student Achievement.

    ERIC Educational Resources Information Center

    Sterbin, Allan; Rakow, Ernest

    The direct effects of locus of control and self-esteem on standardized test scores were studied. The relationships among the standardized test scores and measures of locus of control and self-esteem for 12,260 students from the National Education Longitudinal Study 1994 database were examined, using the same definition of locus of control and…

  10. 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…

  11. The Impact of Locus of Control on Language Achievement

    ERIC Educational Resources Information Center

    Nodoushan, Mohammad Ali Salmani

    2012-01-01

    This study hypothesized that students' loci of control affected their language achievement. 198 (N = 198) EFL students took the Rotter's (1966) locus of control test and were classified as locus-internal (ni = 78), and locus-external (ne = 120). They then took their ordinary courses and at the end of the semester, they were given their exams.…

  12. Identification of Pseudomonas syringae pathogens of Arabidopsis and a bacterial locus determining avirulence on both Arabidopsis and soybean.

    PubMed Central

    Whalen, M C; Innes, R W; Bent, A F; Staskawicz, B J

    1991-01-01

    To develop a model system for molecular genetic analysis of plant-pathogen interactions, we studied the interaction between Arabidopsis thaliana and the bacterial pathogen Pseudomonas syringae pv tomato (Pst). Pst strains were found to be virulent or avirulent on specific Arabidopsis ecotypes, and single ecotypes were resistant to some Pst strains and susceptible to others. In many plant-pathogen interactions, disease resistance is controlled by the simultaneous presence of single plant resistance genes and single pathogen avirulence genes. Therefore, we tested whether avirulence genes in Pst controlled induction of resistance in Arabidopsis. Cosmids that determine avirulence were isolated from Pst genomic libraries, and the Pst avirulence locus avrRpt2 was defined. This allowed us to construct pathogens that differed only by the presence or absence of a single putative avirulence gene. We found that Arabidopsis ecotype Col-0 was susceptible to Pst strain DC3000 but resistant to the same strain carrying avrRpt2, suggesting that a single locus in Col-0 determines resistance. As a first step toward genetically mapping the postulated resistance locus, an ecotype susceptible to infection by DC3000 carrying avrRpt2 was identified. The avrRpt2 locus from Pst was also moved into virulent strains of the soybean pathogen P. syringae pv glycinea to test whether this locus could determine avirulence on soybean. The resulting strains induced a resistant response in a cultivar-specific manner, suggesting that similar resistance mechanisms may function in Arabidopsis and soybean. PMID:1824334

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

    PubMed

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

    2013-12-01

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

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

    PubMed Central

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

    1990-01-01

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

  15. Ancient roots for polymorphism at the HLA-DQ. alpha. locus in primates

    SciTech Connect

    Gyllensten, U.B.; Erlich, H.A. )

    1989-12-01

    The genes encoding the human histocompatibility antigens (HLA) exhibit a remarkable degree of polymorphism as revealed by immunologic and molecular analyses. This extensive sequence polymorphism either may have been generated during the lifetime of the human species or could have arisen before speciation and been maintained in the contemporary human population by selection or, possibly, by genetic drift. These two hypotheses were examined using the polymerase chain reaction method to amplify polymorphic sequences from the DQ{alpha} locus, as well as the DX{alpha} locus, an homologous but nonexpressed locus, in a series of primates that diverged at known times. In general, the amino acid sequence of a specific human DQ{alpha} allelic type is more closely related to its chimpanzee or gorilla counterpart than to other human DQ{alpha} alleles. Phylogenetic analysis of the silent nucleotide position changes shows that the similarity of allelic types between species is due to common ancestry rather than convergent evolution. Thus, most of the polymorphism at the DQ{alpha} locus in the human species was already present at least 5 million years ago in the ancestral species that gave rise to the chimpanzee, gorilla, and human lineages. However, one of the DQ{alpha} alleles may have arisen after speciation by recombination between two ancestral alleles.

  16. Analysis of Recombination Sites within the Maize Waxy Locus

    PubMed Central

    Okagaki, R. J.; Weil, C. F.

    1997-01-01

    Genetic fine structure analysis of the maize wx locus has determined that the ratio of genetic to physical distance within wx was one to two orders of magnitude higher than the average for the maize genome. Similar results have been found at other maize loci. In this study, we examined several mechanisms that could account for this pattern. First, crossovers in two other maize genes resolve preferentially at specific sites. By mapping exchanges between wx-B1 and wx-I relative to a polymorphic SstI site, we found no evidence for such a hotspot at wx. Second, deletion of promoter sequences from wx alleles had little effect on recombination frequencies, in contrast to results in yeast where promoter sequences are important for initiating recombination in some genes. Third, high levels of insertion polymorphism may suppress intergenic recombination. However, the presence of a 2-kb Ds element 470 bp upstream of the wx transcription start site did not further suppress recombination between Ds insertions in nearby wx sequences. Thus, none of these mechanisms is sufficient to explain the difference between intergenic and intragenic recombination rates at wx. PMID:9335616

  17. Genetics of osteoarthritis.

    PubMed

    Rodriguez-Fontenla, Cristina; Gonzalez, Antonio

    2015-01-01

    Osteoarthritis (OA) is a complex disease caused by the interaction of multiple genetic and environmental factors. This review focuses on the studies that have contributed to the discovery of genetic susceptibility factors in OA. The most relevant associations discovered until now are discussed in detail: GDF-5, 7q22 locus, MCF2L, DOT1L, NCOA3 and also some important findings from the arcOGEN study. Moreover, the different approaches that can be used to minimize the specific problems of the study of OA genetics are discussed. These include the study of microsatellites, phenotype standardization and other methods such as meta-analysis of GWAS and gene-based analysis. It is expected that these new approaches contribute to finding new susceptibility genetic factors for OA.

  18. Molecular Identification of the Schwannomatosis Locus

    DTIC Science & Technology

    2004-07-01

    AD Award Number: DAMD17-03-1-0445 TITLE: Molecular Identification of the Schwannomatosis Locus PRINCIPAL INVESTIGATOR: Mia M. MacCollin, M.D...COVERED (Leave blank) July 2004 Annual (1 Jul 2003 - 30 Jun 2004) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Molecular Identification of the Schwannomatosis...linkage and loss of heterozygosity analyses. 3. To determine the molecular mechanism of tumor formation in these patients using complementary molecular

  19. 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.

  20. Genome scan in familial late-onset Alzheimer's disease: a locus on chromosome 6 contributes to age-at-onset.

    PubMed

    Zhao, Wei; Marchani, Elizabeth E; Cheung, Charles Y K; Steinbart, Ellen J; Schellenberg, Gerard D; Bird, Thomas D; Wijsman, Ellen M

    2013-03-01

    Alzheimer's disease (AD) is a common, genetically complex, fatal neurodegenerative disorder of late life. Although several genes are known to play a role in early-onset AD, identification of the genetic basis of late onset AD (LOAD) has been challenging, with only the APOE gene known to have a high contribution to both AD risk and age-at-onset. Here, we present the first genome-scan analysis of the complete, well-characterized University of Washington LOAD sample of 119 pedigrees, using age-at-onset as the trait of interest. The analysis approach used allows for a multilocus trait model while at the same time accommodating age censoring, effects of APOE as a known genetic covariate, and full pedigree and marker information. The results provide strong evidence for linkage of loci contributing to age-at-onset to genomic regions on chromosome 6q16.3, and to 19q13.42 in the region of the APOE locus. There was evidence for interaction between APOE and the locus on chromosome 6q and suggestive evidence for linkage to chromosomes 11p13, 15q12-14, and 19p13.12. These results provide the first independent confirmation of an AD age-at-onset locus on chromosome 6 and suggest that further efforts towards identifying the underlying causal locus or loci are warranted.

  1. Genetic analysis of 12 unrelated CADASIL families: Demonstration of genetic homogeneity: Physical mapping of the gene

    SciTech Connect

    Tournier-Lasserve, E.; Nibbio, A.; Vahedi, K.

    1994-09-01

    CADASIL is the acronym (Cerebral Autosomal Dominant Arteriopathy with Subcortical Ischemic Strokes and Leukoencephalopathy) designating a recently identified mendelian cerebral arteriopathy characterized by the recurrence of ischemic sensory and motor deficits leading to a progressive subcortical dementia. Magnetic resonance imaging of the brain shows extensive areas of increased signal in the hemispheric white matter. We recently mapped the CADASIL locus in 2 large families on chromosome 19 in a 14 cM interval bracketed by D19S221 and D19S215{sup *}. Forty additional families have been collected. Twelve of them including more than 200 members have already been genotyped with a set of 10 highly polymorphic markers located between D19S221 and D19S215. All families are significantly linked to chromosome 19 demonstrating genetic homogeneity. Combined lod scores for several of these markers are above 30. The size of the mapping interval has been reduced to 2 cM. Genetic testing for presymptomatic individuals is now possible with respect to all ethical rules in this severe condition. Lastly, physical mapping of the affected gene has been started and data will be presented at the meeting.

  2. A robust multiple-locus method for quantitative trait locus analysis of non-normally distributed multiple traits.

    PubMed

    Li, Z; Möttönen, J; Sillanpää, M J

    2015-12-01

    Linear regression-based quantitative trait loci/association mapping methods such as least squares commonly assume normality of residuals. In genetics studies of plants or animals, some quantitative traits may not follow normal distribution because the data include outlying observations or data that are collected from multiple sources, and in such cases the normal regression methods may lose some statistical power to detect quantitative trait loci. In this work, we propose a robust multiple-locus regression approach for analyzing multiple quantitative traits without normality assumption. In our method, the objective function is least absolute deviation (LAD), which corresponds to the assumption of multivariate Laplace distributed residual errors. This distribution has heavier tails than the normal distribution. In addition, we adopt a group LASSO penalty to produce shrinkage estimation of the marker effects and to describe the genetic correlation among phenotypes. Our LAD-LASSO approach is less sensitive to the outliers and is more appropriate for the analysis of data with skewedly distributed phenotypes. Another application of our robust approach is on missing phenotype problem in multiple-trait analysis, where the missing phenotype items can simply be filled with some extreme values, and be treated as outliers. The efficiency of the LAD-LASSO approach is illustrated on both simulated and real data sets.

  3. CTF Meeting 2012: Translation of the Basic Understanding of the Biology and Genetics of NF1, NF2, and Schwannomatosis Toward the Development of Effective Therapies

    PubMed Central

    Widemann, Brigitte C.; Acosta, Maria T.; Ammoun, Sylvia; Belzberg, Allan J.; Bernards, Andre; Blakeley, Jaishri; Bretscher, Antony; Cichowski, Karen; Clapp, D. Wade; Dombi, Eva; Evans, Gareth D.; Ferner, Rosalie; Fernandez-Valle, Cristina; Fisher, Michael J.; Giovannini, Marco; Gutmann, David H.; Hanemann, C. Oliver; Hennigan, Robert; Huson, Susan; Ingram, David; Kissil, Joe; Korf, Bruce R.; Legius, Eric; Packer, Roger J.; McClatchey, Andrea I; McCormick, Frank; North, Kathryn; Pehrsson, Minja; Plotkin, Scott R.; Ramesh, Vijaya; Ratner, Nancy; Schirmer, Susann; Sherman, Larry; Schorry, Elizabeth; Stevenson, David; Stewart, Douglas R.; Ullrich, Nicole; Bakker, Annette C.; Morrison, Helen

    2014-01-01

    The neurofibromatoses (NF) are autosomal dominant genetic disorders that encompass the rare diseases NF1, NF2, and schwannomatosis. The NFs affect more people worldwide than Duchenne muscular dystrophy and Huntington's disease combined. NF1 and NF2 are caused by mutations of known tumor suppressor genes (NF1 and NF2, respectively). For schwannomatosis, although mutations in SMARCB1 were identified in a subpopulation of schwannomatosis patients, additional causative gene mutations are still to be discovered. Individuals with NF1 may demonstrate manifestations in multiple organ systems, including tumors of the nervous system, learning disabilities, and physical disfigurement. NF2 ultimately can cause deafness, cranial nerve deficits, and additional severe morbidities caused by tumors of the nervous system. Unmanageable pain is a key finding in patients with schwannomatosis. Although today there is no marketed treatment for NF-related tumors, a significant number of clinical trials have become available. In addition, significant preclinical efforts have led to a more rational selection of potential drug candidates for NF trials. An important element in fueling this progress is the sharing of knowledge. For over 20 years the Children's Tumor Foundation has convened an annual NF Conference, bringing together NF professionals to share novel findings, ideas, and build collaborations. The 2012 NF Conference held in New Orleans hosted over 350 NF researchers and clinicians. This article provides a synthesis of the highlights presented at the conference and as such, is a “state-of-the-field” for NF research in 2012. PMID:24443315

  4. CTF meeting 2012: Translation of the basic understanding of the biology and genetics of NF1, NF2, and schwannomatosis toward the development of effective therapies.

    PubMed

    Widemann, Brigitte C; Acosta, Maria T; Ammoun, Sylvia; Belzberg, Allan J; Bernards, Andre; Blakeley, Jaishri; Bretscher, Antony; Cichowski, Karen; Clapp, D Wade; Dombi, Eva; Evans, Gareth D; Ferner, Rosalie; Fernandez-Valle, Cristina; Fisher, Michael J; Giovannini, Marco; Gutmann, David H; Hanemann, C Oliver; Hennigan, Robert; Huson, Susan; Ingram, David; Kissil, Joe; Korf, Bruce R; Legius, Eric; Packer, Roger J; McClatchey, Andrea I; McCormick, Frank; North, Kathryn; Pehrsson, Minja; Plotkin, Scott R; Ramesh, Vijaya; Ratner, Nancy; Schirmer, Susann; Sherman, Larry; Schorry, Elizabeth; Stevenson, David; Stewart, Douglas R; Ullrich, Nicole; Bakker, Annette C; Morrison, Helen

    2014-03-01

    The neurofibromatoses (NF) are autosomal dominant genetic disorders that encompass the rare diseases NF1, NF2, and schwannomatosis. The NFs affect more people worldwide than Duchenne muscular dystrophy and Huntington's disease combined. NF1 and NF2 are caused by mutations of known tumor suppressor genes (NF1 and NF2, respectively). For schwannomatosis, although mutations in SMARCB1 were identified in a subpopulation of schwannomatosis patients, additional causative gene mutations are still to be discovered. Individuals with NF1 may demonstrate manifestations in multiple organ systems, including tumors of the nervous system, learning disabilities, and physical disfigurement. NF2 ultimately can cause deafness, cranial nerve deficits, and additional severe morbidities caused by tumors of the nervous system. Unmanageable pain is a key finding in patients with schwannomatosis. Although today there is no marketed treatment for NF-related tumors, a significant number of clinical trials have become available. In addition, significant preclinical efforts have led to a more rational selection of potential drug candidates for NF trials. An important element in fueling this progress is the sharing of knowledge. For over 20 years the Children's Tumor Foundation has convened an annual NF Conference, bringing together NF professionals to share novel findings, ideas, and build collaborations. The 2012 NF Conference held in New Orleans hosted over 350 NF researchers and clinicians. This article provides a synthesis of the highlights presented at the conference and as such, is a "state-of-the-field" for NF research in 2012.

  5. Nice to meet you: genetic, epigenetic and metabolic controls of plant perception of beneficial associative and endophytic diazotrophic bacteria in non-leguminous plants.

    PubMed

    Carvalho, T L G; Ballesteros, H G F; Thiebaut, F; Ferreira, P C G; Hemerly, A S

    2016-04-01

    A wide range of rhizosphere diazotrophic bacteria are able to establish beneficial associations with plants, being able to associate to root surfaces or even endophytically colonize plant tissues. In common, both associative and endophytic types of colonization can result in beneficial outcomes to the plant leading to plant growth promotion, as well as increase in tolerance against biotic and abiotic stresses. An intriguing question in such associations is how plant cell surface perceives signals from other living organisms, thus sorting pathogens from beneficial ones, to transduce this information and activate proper responses that will finally culminate in plant adaptations to optimize their growth rates. This review focuses on the recent advances in the understanding of genetic and epigenetic controls of plant-bacteria signaling and recognition during beneficial associations with associative and endophytic diazotrophic bacteria. Finally, we propose that "soil-rhizosphere-rhizoplane-endophytes-plant" could be considered as a single coordinated unit with dynamic components that integrate the plant with the environment to generate adaptive responses in plants to improve growth. The homeostasis of the whole system should recruit different levels of regulation, and recognition between the parties in a given environment might be one of the crucial factors coordinating these adaptive plant responses.

  6. 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.

  7. Gametophytic self-incompatibility is controlled by a single major locus on chromosome 1 in Lycopersicon peruvianum

    PubMed Central

    Tanksley, Steven D.; Loaiza-Figueroa, Fernando

    1985-01-01

    By using a number of previously mapped enzyme-coding genes as genetic markers, it has been possible to scan the genome of Lycopersicon peruvianum for gene(s) controlling the gametophytic self-incompatibility reaction. Regardless of genetic background or level of inbreeding, only a single locus (S), mapping to chromosome 1, was found to control the self-incompatibility reaction. Despite the widespread occurrence of this form of self-incompatibility in higher plants, to the best of our knowledge, the locus underlying the response has not been confirmed previously through genetic mapping, and the results cast doubts on hypotheses requiring multifactoral or dynamic control of gametophytic self-incompatibility. PMID:16593587

  8. A gene locus for targeted ectopic gene integration in Zymoseptoria tritici☆

    PubMed Central

    Kilaru, S.; Schuster, M.; Latz, M.; Das Gupta, S.; Steinberg, N.; Fones, H.; Gurr, S.J.; Talbot, N.J.; Steinberg, G.

    2015-01-01

    Understanding the cellular organization and biology of fungal pathogens requires accurate methods for genomic integration of mutant alleles or fluorescent fusion-protein constructs. In Zymoseptoria tritici, this can be achieved by integrating of plasmid DNA randomly into the genome of this wheat pathogen. However, untargeted ectopic integration carries the risk of unwanted side effects, such as altered gene expression, due to targeting regulatory elements, or gene disruption following integration into protein-coding regions of the genome. Here, we establish the succinate dehydrogenase (sdi1) locus as a single “soft-landing” site for targeted ectopic integration of genetic constructs by using a carboxin-resistant sdi1R allele, carrying the point-mutation H267L. We use various green and red fluorescent fusion constructs and show that 97% of all transformants integrate correctly into the sdi1 locus as single copies. We also demonstrate that such integration does not affect the pathogenicity of Z. tritici, and thus the sdi1 locus is a useful tool for virulence analysis in genetically modified Z. tritici strains. Furthermore, we have developed a vector which facilitates yeast recombination cloning and thus allows assembly of multiple overlapping DNA fragments in a single cloning step for high throughput vector and strain generation. PMID:26092798

  9. Evidence for locus heterogeneity in human autosomal dominant split hand/split foot malformation

    SciTech Connect

    Palmer, S.E.; Wijsman, E.M.; Stephens, K.; Evans, J.P. ); Scherer, S.W.; Tsui, L.C. ); Kukolich, M. )

    1994-07-01

    Split hand/split foot (SHSF; also known as ectrodactyly) is a human developmental disorder characterized by missing central digits and other distal limb malformations. An association between SHSF and cytogenetically visible rearrangements of chromosome 7 at bands q21-q22 provides compelling evidence for the location of a causative gene at this location, and the locus has been designated SHFD1. In the present study, marker loci were localized to the SHFD1 critical region through the analysis of somatic cell hybrids derived from individuals with SHSF and cytogenetic abnormalities involving the 7q21-q22 region. Combined genetic and physical data suggest that the order of markers in the SHFD1 critical region is cen-D7S492-D7S527-(D7S479-D7S491)-SHFD1-D7S553-D7S518-qter. Dinucleotide repeat polymorphisms at three of these loci were used to test for linkage of SHSF to this region in a large pedigree that demonstrates autosomal dominant SHSF. Evidence against linkage of the SHSF gene to 7q21-q22 was obtained in this pedigree. Therefore, combined molecular and genetic data provide evidence for locus heterogeneity in autosomal dominant SHSF. The authors propose the name SHSF2 for this second locus. 34 refs., 4 figs., 1 tab.

  10. Analysis of allelic variation of the apolipoprotein B hypervariable locus in the Bashkir and Komi populations

    SciTech Connect

    Khusnutdinova, E.K.; Khidiatova, I.M.; Rafikov, H.S.

    1995-07-01

    Allelic variation of the hypervariable apolipoprotein B gene locus (APOB) in three groups of the Bashkir population and in the Komi population was analyzed. Among 219 individuals studied, 13 allelic variants were identified with a number of repeats ranging from 28 to 52. The frequency of alleles varied from 0.01 to 0.51 with the mean heterozygosity index being 0.66 in the Bashkir population and 0.74 in the Komi one. Considerable difference in the frequency distribution of the APOB loci genotypes between the Bashkir and Komi populations was observed, and the distribution patterns for Bashkirs from Abzelilovskii and Ilishevskii raions deviated from the Hardy-Weinberg equilibrium. The genetic distance between the Bashkir and Komi populations calculated on the basis of allele frequencies at the hypervariable APOB gene locus corresponded to the expected degree similarity of the population studied. Thus, this locus can be recommended as an informative marker for studying the gene pool and genetic processes in the populations because of the high level of its polymorphism and the heterozygosity in the populations. 19 refs., 1 fig., 4 tabs.

  11. TRANSLATING ECOLOGY, PHYSIOLOGY, BIOCHEMISTRY, AND POPULATION GENETICS RESEARCH TO MEET THE CHALLENGE OF TICK AND TICK-BORNE DISEASES IN NORTH AMERICA.

    PubMed

    Esteve-Gassent, Maria D; Castro-Arellano, Ivan; Feria-Arroyo, Teresa P; Patino, Ramiro; Li, Andrew Y; Medina, Raul F; de León, Adalberto A Pérez; Rodríguez-Vivas, Roger Iván

    2016-05-01

    Emerging and re-emerging tick-borne diseases threaten public health and the wellbeing of domestic animals and wildlife globally. The adoption of an evolutionary ecology framework aimed to diminish the impact of tick-borne diseases needs to be part of strategies to protect human and animal populations. We present a review of current knowledge on the adaptation of ticks to their environment, and the impact that global change could have on their geographic distribution in North America. Environmental pressures will affect tick population genetics by selecting genotypes able to withstand new and changing environments and by altering the connectivity and isolation of several tick populations. Research in these areas is particularly lacking in the southern United States and most of Mexico with knowledge gaps on the ecology of these diseases, including a void in the identity of reservoir hosts for several tick-borne pathogens. Additionally, the way in which anthropogenic changes to landscapes may influence tick-borne disease ecology remains to be fully understood. Enhanced knowledge in these areas is needed in order to implement effective and sustainable integrated tick management strategies. We propose to refocus ecology studies with emphasis on metacommunity-based approaches to enable a holistic perspective addressing whole pathogen and host assemblages. Network analyses could be used to develop mechanistic models involving multihost-pathogen communities. An increase in our understanding of the ecology of tick-borne diseases across their geographic distribution will aid in the design of effective area-wide tick control strategies aimed to diminish the burden of pathogens transmitted by ticks.

  12. 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.

  13. Genetics and molecular biology of breast cancer

    SciTech Connect

    King, M.C.; Lippman, M.

    1992-12-31

    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  14. Two-locus models of disease: Comparison of likelihood and nonparametric linkage methods

    SciTech Connect

    Goldin, L.R. ); Weeks, D.E. )

    1993-10-01

    The power to detect linkage for likelihood and nonparametric (Haseman-Elston, affected-sib-pair, and affected-pedigree-member) methods is compared for the case of a common, dichotomous trait resulting from the segregation of two loci. Pedigree data for several two-locus epistatic and heterogeneity models have been simulated, with one of the loci linked to a marker locus. Replicate samples of 20 three-generation pedigrees (16 individuals/pedigree) were simulated and then ascertained for having at least 6 affected individuals. The power of linkage detection calculated under the correct two-locus model is only slightly higher than that under a single locus model with reduced penetrance. As expected, the nonparametric linkage methods have somewhat lower power than does the lod-score method, the difference depending on the mode of transmission of the linked locus. Thus, for many pedigree linkage studies, the lod-score method will have the best power. However, this conclusion depends on how many times the lod score will be calculated for a given marker. The Haseman-Elston method would likely be preferable to calculating lod scores under a large number of genetic models (i.e., varying both the mode of transmission and the penetrances), since such an analysis requires an increase in the critical value of the lod criterion. The power of the affected-pedigree-member method is lower than the other methods, which can be shown to be largely due to the fact that marker genotypes for unaffected individuals are not used. 31 refs., 1 fig., 5 tabs.

  15. 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.

  16. The mutY gene: a mutator locus in Escherichia coli that generates G.C----T.A transversions.

    PubMed

    Nghiem, Y; Cabrera, M; Cupples, C G; Miller, J H

    1988-04-01

    We have used a strain with an altered lacZ gene, which reverts to wild type via only certain transversions, to detect transversion-specific mutators in Escherichia coli. Detection relied on a papillation technique that uses a combination of beta-galactosides to reveal blue Lac+ papillae. One class of mutators is specific for the G.C----T.A transversion as determined by the reversion pattern of a set of lacZ mutations and by the distribution of forward nonsense mutations in the lacI gene. The locus responsible for the mutator phenotype is designated mutY and maps near 64 min on the genetic map of E. coli. The mutY locus may act in a similar but reciprocal fashion to the previously characterized mutT locus, which results in A.T----C.G transversions.

  17. Analysis of microsatellite polymorphisms within the GLC1F locus in Japanese patients with normal tension glaucoma

    PubMed Central

    Murakami, Kaori; Ota, Masao; Shiota, Tomoko; Nomura, Naoko; Kashiwagi, Kenji; Mabuchi, Fumihiko; Iijima, Hiroyuki; Kawase, Kazuhide; Yamamoto, Tetsuya; Nakamura, Makoto; Negi, Akira; Sagara, Takeshi; Nishida, Teruo; Inatani, Masaru; Tanihara, Hidenobu; Aihara, Makoto; Araie, Makoto; Fukuchi, Takeo; Abe, Haruki; Higashide, Tomomi; Sugiyama, Kazuhisa; Kanamoto, Takashi; Kiuchi, Yoshiaki; Iwase, Aiko; Ohno, Shigeaki; Inoko, Hidetoshi; Mizuki, Nobuhisa

    2010-01-01

    Purpose To investigate whether the GLC1F locus is associated with normal tension glaucoma (NTG) in Japanese patients. Methods We recruited 242 unrelated Japanese subjects, including, 141 NTG patients and 101 healthy controls. The patients exhibiting a comparatively early onset were selected as they suggest that genetic factors may show stronger involvement. Genotyping and assessment of allelic diversity was performed on 11 highly polymorphic microsatellite markers in and around the GLC1F locus. Results Individuals carrying the 163 allele of D7S1277i had a statistically significant increased risk of NTG (p=0.0013, pc=0.016, OR=2.47, 95%CI=1.42–4.30). None of the other markers identified significant loci (pc>0.05) after Bonferroni’s correction. Conclusions These findings suggested that the genes in the GLC1F locus may be associated with the pathogenesis of NTG. PMID:20309402

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

    PubMed Central

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

    2012-01-01

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

  19. Assignment of the norepinephrine transporter protein (NET1) locus to chromosome 16

    SciTech Connect

    Gelernter, J.; Kruger, S. ); Kidd, K.K.; Pakstis, A.J.; Pacholczyk, T. ); Sparkes, R.S. ); Amara, S. )

    1993-12-01

    The norepinephrine transporter protein (NET) is the presynaptic reuptake site for norepinephrine and a site of action for several drugs with CNS effects, some of which are therapeutically useful and some of which are drugs of abuse. The authors used PCR with a somatic cell hybrid panel to obtain a provisional assignment to chromosome 16. They then typed a genetic polymorphism at the NET1 locus in three large multigenerational families and used linkage analysis to confirm the preliminary assignment and to refine the localization to 16q, near the HP locus. Finally, they typed the NET1 RFLP, on the CEPH families and the additional linkage data localized NET1 to 16q13-q21, flanked by D16S71 (centromerically) and HP (telomerically). 11 refs., 2 tabs.

  20. 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.

  1. The genetics of deafness.

    PubMed

    Nance, Walter E

    2003-01-01

    Deafness is an etiologically heterogeneous trait with many known genetic and environmental causes. Genetic factors account for at least half of all cases of profound congenital deafness, and can be classified by the mode of inheritance and the presence or absence of characteristic clinical features that may permit the diagnosis of a specific form of syndromic deafness. The identification of more than 120 independent genes for deafness has provided profound new insights into the pathophysiology of hearing, as well as many unexpected surprises. Although a large number of genes can clearly cause deafness, recessive mutations at a single locus, GJB2 or Connexin 26, account for more than half of all genetic cases in some, but not all populations. The high frequency may well be related to the greatly improved social, educational, and economic circumstances of the deaf that began with the introduction of sign language 300-400 years ago, along with a high frequency of marriages among the deaf in many countries. Similar mechanisms may account for the rapid fixation of genes for speech after the first mutations appeared 50,000-100,000 years ago. Molecular studies have shown that mutations involving several different loci may be the cause for the same form of syndromic deafness. Even within a single locus, different mutations can have profoundly different effects, leading to a different pattern of inheritance in some cases, or isolated hearing loss without the characteristic syndromic features in others. Most cases of genetic deafness result from mutations at a single locus, but an increasing number of examples are being recognized in which recessive mutations at two loci are involved. For example, digenic interactions are now known to be an important cause of deafness in individuals who carry a single mutation at the Connexin 26 locus along with a deletion involving the functionally related Connexin 30 locus. This mechanism complicates genetic evaluation and counseling, but

  2. Multi-locus Analyses Reveal Four Giraffe Species Instead of One.

    PubMed

    Fennessy, Julian; Bidon, Tobias; Reuss, Friederike; Kumar, Vikas; Elkan, Paul; Nilsson, Maria A; Vamberger, Melita; Fritz, Uwe; Janke, Axel

    2016-09-26

    Traditionally, one giraffe species and up to eleven subspecies have been recognized [1]; however, nine subspecies are commonly accepted [2]. Even after a century of research, the distinctness of each giraffe subspecies remains unclear, and the genetic variation across their distribution range has been incompletely explored. Recent genetic studies on mtDNA have shown reciprocal monophyly of the matrilines among seven of the nine assumed subspecies [3, 4]. Moreover, until now, genetic analyses have not been applied to biparentally inherited sequence data and did not include data from all nine giraffe subspecies. We sampled natural giraffe populations from across their range in Africa, and for the first time individuals from the nominate subspecies, the Nubian giraffe, Giraffa camelopardalis camelopardalis Linnaeus 1758 [5], were included in a genetic analysis. Coalescence-based multi-locus and population genetic analyses identify at least four separate and monophyletic clades, which should be recognized as four distinct giraffe species under the genetic isolation criterion. Analyses of 190 individuals from maternal and biparental markers support these findings and further suggest subsuming Rothschild's giraffe into the Nubian giraffe, as well as Thornicroft's giraffe into the Masai giraffe [6]. A giraffe survey genome produced valuable data from microsatellites, mobile genetic elements, and accurate divergence time estimates. Our findings provide the most inclusive analysis of giraffe relationships to date and show that their genetic complexity has been underestimated, highlighting the need for greater conservation efforts for the world's tallest mammal.

  3. The Superantigen Gene ypm Is Located in an Unstable Chromosomal Locus of Yersinia pseudotuberculosis

    PubMed Central

    Carnoy, Christophe; Floquet, Stephanie; Marceau, Michael; Sebbane, Florent; Haentjens-Herwegh, Stephanie; Devalckenaere, Annie; Simonet, Michel

    2002-01-01

    Yersinia pseudotuberculosis produces YPM (Y. pseudotuberculosis-derived mitogen), a superantigenic toxin that exacerbates the virulence of the bacterium in vivo. To date, three alleles of the superantigen gene (ypmA, ypmB, and ypmC) have been described. These genes are not found in all Y. pseudotuberculosis strains and have a low GC content, suggesting their location on mobile genetic elements. To elucidate this question, the genetic environment of the superantigen-encoding genes was characterized and 11 open reading frames (ORFs) were defined. Sequence analysis revealed that the ypm genes were not associated with plasmids, phages, transposons, or pathogenicity islands and that the superantigen genes were always located in the chromosome between ORF3 and ORF4. Nonsuperantigenic strains exhibited the same genetic organization of the locus but lacked the ypm gene between ORF3 and ORF4. A new insertion sequence, designated IS1398, which displays features of the Tn3 family, was characterized downstream of the ypmA and ypmC genes. A 13.3-kb region containing the ypm genes was not found in the genome of Y. pestis (CO92 and KIM 5 strains). We experimentally induced deletion of the ypm gene from a superantigen-expressing Y. pseudotuberculosis: using the association of aph(3′)-IIIa and sacB genes, we demonstrated that when these reporter genes were present in the ypm locus, deletion of these genes was about 250 times more frequent than when they were located in another region of the Y. pseudotuberculosis chromosome. These results indicate that unlike other superantigenic toxin genes, the Yersinia ypm genes are not associated with mobile genetic elements but are inserted in an unstable locus of the genome. PMID:12142419

  4. 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.

  5. A root locus based flutter synthesis procedure

    NASA Technical Reports Server (NTRS)

    Hajela, P.

    1983-01-01

    An efficient generalized constraint is proposed in the context of a nonlinear mathematical programming approach for the minimum weight design of wing structures for flutter considerations. The approach is based on a root locus analysis procedure that is better suited for flutter redesign than the conventionally used V-g method. The proposed flutter constraint does not require an actual computation of the flutter speed, allows prescription of meaningful margins of safety in the optimized design and lends itself to elegant computation of sensitivity information. The approach is implemented and results presented for representative structural models.

  6. Root Locus Algorithms for Programmable Pocket Calculators

    NASA Technical Reports Server (NTRS)

    Wechsler, E. R.

    1983-01-01

    Two algorithms are described which allow the plotting of individual points on a root locus diagram with or without time delay. The development was performed during the design of a continuous phase shifter used in the Baseband Antenna Combiner for the Deep Space Network (DSN). The algorithms, which are expected to be useful in similar DSN efforts, are simple enough to be implemented on a programmable pocket calculator. The coordinates of the open-loop zeros and poles, the gain constant K, and the time delay T are the data inputs.

  7. The APOE locus advances disease progression in late onset familial Alzheimer`s disease but is not causative

    SciTech Connect

    Crawford, F.; Bennett, C.; Osborne, A.

    1994-09-01

    An association has been observed in several independent data sets between late onset Alzheimer`s disease (AD) and the APOE locus on chromosomes 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the {epsilon}4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and nonstringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease-free survival suggested that APOE genotype contributes a small fraction of the total variance, indicating that the APOE locus is a poor predictor of disease-free survival time within late onset families. We suggest that the APOE locus enhances the rate of progression of the disease in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause this disease.

  8. 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

  9. Evidence of genotypic adaptation to the exposure to volcanic risk at the dopamine receptor DRD4 locus

    PubMed Central

    Faurie, Charlotte; Mettling, Clement; Ali Bchir, Mohamed; Hadmoko, Danang Sri; Heitz, Carine; Lestari, Evi Dwi; Raymond, Michel; Willinger, Marc

    2016-01-01

    Humans have colonized and adapted to extremely diverse environments, and the genetic basis of some such adaptations, for example to high altitude, is understood. In some cases, local or regional variation in selection pressure could also cause behavioural adaptations. Numerous genes influence behaviour, such as alleles at the dopamine receptor locus D4 (DRD4), which are associated with attitude toward risk in experimental settings. We demonstrate genetic differentiation for this gene, but not for five unlinked microsatellite loci, between high- and low risk environments around Mount Merapi, an active volcano in Java, Indonesia. Using a behavioural experiment, we further show that people inhabiting the high risk environment are significantly more risk averse. We provide evidence of a genetic basis for this difference, showing that heterozygotes at the DRD4 locus are more risk averse than either homozygotes. In the high risk environment, allele frequencies are equilibrated, generating a high frequency of heterozygotes. Thus it appears that overdominance (i.e. selective advantage of heterozygotes) generates negative frequency dependent selection, favouring the rarer allele at this locus. Our results therefore provide evidence for adaptation to a marginal habitat through the selection of a neurocognitive trait with a genetic basis. PMID:27905471

  10. Evidence of genotypic adaptation to the exposure to volcanic risk at the dopamine receptor DRD4 locus.

    PubMed

    Faurie, Charlotte; Mettling, Clement; Ali Bchir, Mohamed; Hadmoko, Danang Sri; Heitz, Carine; Lestari, Evi Dwi; Raymond, Michel; Willinger, Marc

    2016-12-01

    Humans have colonized and adapted to extremely diverse environments, and the genetic basis of some such adaptations, for example to high altitude, is understood. In some cases, local or regional variation in selection pressure could also cause behavioural adaptations. Numerous genes influence behaviour, such as alleles at the dopamine receptor locus D4 (DRD4), which are associated with attitude toward risk in experimental settings. We demonstrate genetic differentiation for this gene, but not for five unlinked microsatellite loci, between high- and low risk environments around Mount Merapi, an active volcano in Java, Indonesia. Using a behavioural experiment, we further show that people inhabiting the high risk environment are significantly more risk averse. We provide evidence of a genetic basis for this difference, showing that heterozygotes at the DRD4 locus are more risk averse than either homozygotes. In the high risk environment, allele frequencies are equilibrated, generating a high frequency of heterozygotes. Thus it appears that overdominance (i.e. selective advantage of heterozygotes) generates negative frequency dependent selection, favouring the rarer allele at this locus. Our results therefore provide evidence for adaptation to a marginal habitat through the selection of a neurocognitive trait with a genetic basis.

  11. Relationships between locus of control and paranormal beliefs.

    PubMed

    Newby, Robert W; Davis, Jessica Boyette

    2004-06-01

    The present study investigated the associations between scores on paranormal beliefs, locus of control, and certain psychological processes such as affect and cognitions as measured by the Linguistic Inquiry and Word Count. Analysis yielded significant correlations between scores on Locus of Control and two subscales of Tobacyk's (1988) Revised Paranormal Beliefs Scale, New Age Philosophy and Traditional Paranormal Beliefs. A step-wise multiple regression analysis indicated that Locus of Control was significantly related to New Age Philosophy. Other correlations were found between Tobacyk's subscales, Locus of Control, and three processes measured by the Linguistic Inquiry and Word Count.

  12. Impact of locus of control on health message effectiveness.

    PubMed

    Kong, Ying; Shen, Fuyuan

    2011-10-01

    This article examined how individuals' locus of control might moderate the effect of health message frames. An experiment was conducted whereby participants read either individual- or social-responsibility message frames after their locus of control was primed. Results indicated that messages presented in individual-responsibility frames were more persuasive when people were primed with internal locus of control, whereas social-responsibility framed appeals were more persuasive when people were primed with external locus of control. These results were found for individuals in both high and low cognitive load conditions. Theoretical and practical implications of the findings are discussed.

  13. 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.

  14. Familial migraine: Exclusion of the susceptibility gene from the reported locus of familial hemiplegic migraine on 19p

    SciTech Connect

    Hovatta, I.; Peltonen, L.; Kallela, M.; Faerkkilae, M.

    1994-10-01

    Genetic isolates are highly useful in analyses of the molecular background of complex diseases since the enrichment of a limited number of predisposing genes can be predicted in representative families or in specific geographical regions. It has been suggested that the pathophysiology and etiology of familial hemiplegic migraine (FHM) and typical migraine with aura are most probably the same. Recent assignment of FHM locus to chromosome 19p in two French families makes it now possible to test this hypothesis. We report here linkage data on four families with multiple cases of migraine disorder originating from the genetically isolated population of Finland. We were interested to discover whether the migraine in these families would also show linkage to the markers on 19p. We could exclude a region of 50 cM, flanking the reported FHM locus, as a site of migraine locus in our four families. It seems evident that locus heterogeneity exists between different diagnostic classes of migraine spectrum of diseases and also between different ethnic groups. 10 refs., 2 figs., 1 tab.

  15. 76 FR 7569 - Public Meeting of the Presidential Commission for the Study of Bioethical Issues

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-10

    ... Commission will discuss genetics, neuroscience, and neuroimaging for testing, research, diagnosis, risk... actions as appropriate. The main agenda items for this fourth meeting involve genetics, neuroscience, and... exploring social and ethical issues involving genetics, neuroscience, and neuroimaging used for...

  16. Mutations Affecting Expression of the rosy Locus in Drosophila melanogaster

    PubMed Central

    Lee, Chong Sung; Curtis, Daniel; McCarron, Margaret; Love, Carol; Gray, Mark; Bender, Welcome; Chovnick, Arthur

    1987-01-01

    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. We have determined the DNA sequence of this region from both genomic and cDNA clones, and from the ry+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. We 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 (T. P. Keith et al. 1987), 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. PMID:3036645

  17. A Quantitative Trait Locus on chr.4 Regulates Thymic Involution

    PubMed Central

    Kumar, Ritu; Avagyan, Serine

    2010-01-01

    The mechanisms underlying age-associated thymic involution are unknown. In mice, thymic involution shows mouse strain–dependent genetic variation. Identification of the underlying genes would provide mechanistic insight into this elusive process. We previously showed that responsiveness of hematopoietic stem and progenitor cells (HSPCs) to transforming growth factor-beta 2, a positive regulator of HSPC proliferation, is regulated by a quantitative trait locus (QTL) on chr. 4, Tb2r1. Interestingly, Tgfb2+/− mice have delayed thymic involution. Therefore, we tested the hypothesis that a QTL on chr. 4 might regulate thymic involution. Aged, but not young, B6.D2-chr.4 congenic mice, where the telomeric region of chr. 4 was introgressed from DBA/2 to C57BL/6 mice, had larger thymi, and better maintenance of early thymic precursors than C57BL/6 control mice. These observations unequivocally demonstrate that the telomeric region of chr. 4 contains a QTL, Ti1 (thymic involution 1) that regulates thymic involution, and suggest the possibility that Ti1 may be identical to Tb2r1. PMID:20371546

  18. The functional organization of the vestigial locus in Drosophila melanogaster.

    PubMed

    Williams, J A; Atkin, A L; Bell, J B

    1990-03-01

    Vestigial mutants are associated with imaginal disc cell death which results in the deletion of adult wing and haltere structures. The vestigial locus has previously been cloned, and mutational lesions associated with a number of vg alleles were mapped within a 19 kb DNA region defined as essential for vg function. Herein we report the identification and characterization of a developmentally regulated 3.8 kb vg transcript which is spliced from exons distributed throughout the essential interval defined above. All the characterized classical alleles have predictable effects on this transcription unit, and the severity of this effect is directly proportional to the severity of the wing phenotype. A repetitive domain within this transcription unit was identified and may serve as a tag to isolate other genes with functions related to vg. We also report an exceptional vg allele (vg83b27) that produces an extreme wing and haltere phenotype, but which defines a second vg complementation unit. This allele is associated with a 4 kb deletion entirely within a 4.5 kb vg intron as defined by the 3.8 kb transcription unit. Molecular and genetic evidence indicates that the vg83b27 mutation has a functional 3.8 kb transcription unit, thus accounting for its ability to complement classical alleles. The results indicate that sequences within a vg intron are essential for normal wing and haltere development.

  19. 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.

  20. Staff meeting

    ScienceCinema

    None

    2016-07-12

    I would like to invite all members of the CERN Personnel to a meeting on Wednesday 16 January 2008 at 3:00 p.m. Main Auditorium (bldg 500) to convey my best wishes for the new year, to review CERN’s activities during 2007 and to present the perspectives for 2008, the year of the LHC start-up. Closed-circuit transmission of the meeting will be available in the Council Chamber and in the AB Auditorium (Meyrin), the AB Auditorium (Prévessin), the IT Auditorium (Bldg. 31) and the AT Auditorium (Bldg. 30). Simultaneous translation into English will be available in the main Auditorium. Best wishes for the festive season! Robert AYMAR

  1. Meeting information

    NASA Astrophysics Data System (ADS)

    The 1986 Ocean Sciences Meeting of the American Geophysical Union and the American Society of Limnology and Oceanography (ASLO) will be held January 13-17, 1986, in New Orleans, La., at the Fairmont Hotel. Co-sponsoring societies are the Acoustical Society of America (ASA), the American Meteorological Society (AMS), the Marine Technology Society (MTS), and the Institute of Electrical and Electronics Engineers, Oceanic Engineering Society (OES).

  2. 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

  3. Conservation of the S10-spc-α Locus within Otherwise Highly Plastic Genomes Provides Phylogenetic Insight into the Genus Leptospira

    PubMed Central

    Zuerner, Richard L.; Ahmed, Niyaz; Bulach, Dieter M.; Quinteiro, Javier; Hartskeerl, Rudy A.

    2008-01-01

    S10-spc-α is a 17.5 kb cluster of 32 genes encoding ribosomal proteins. This locus has an unusual composition and organization in Leptospira interrogans. We demonstrate the highly conserved nature of this region among diverse Leptospira and show its utility as a phylogenetically informative region. Comparative analyses were performed by PCR using primer sets covering the whole locus. Correctly sized fragments were obtained by PCR from all L. interrogans strains tested for each primer set indicating that this locus is well conserved in this species. Few differences were detected in amplification profiles between different pathogenic species, indicating that the S10-spc-α locus is conserved among pathogenic Leptospira. In contrast, PCR analysis of this locus using DNA from saprophytic Leptospira species and species with an intermediate pathogenic capacity generated varied results. Sequence alignment of the S10-spc-α locus from two pathogenic species, L. interrogans and L. borgpetersenii, with the corresponding locus from the saprophyte L. biflexa serovar Patoc showed that genetic organization of this locus is well conserved within Leptospira. Multilocus sequence typing (MLST) of four conserved regions resulted in the construction of well-defined phylogenetic trees that help resolve questions about the interrelationships of pathogenic Leptospira. Based on the results of secY sequence analysis, we found that reliable species identification of pathogenic Leptospira is possible by comparative analysis of a 245 bp region commonly used as a target for diagnostic PCR for leptospirosis. Comparative analysis of Leptospira strains revealed that strain H6 previously classified as L. inadai actually belongs to the pathogenic species L. interrogans and that L. meyeri strain ICF phylogenetically co-localized with the pathogenic clusters. These findings demonstrate that the S10-spc-α locus is highly conserved throughout the genus and may be more useful in comparing evolution of

  4. 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.

  5. Genome wide analysis of inbred mouse lines identifies a locus containing Ppar-gamma as contributing to enhanced malaria survival.

    PubMed

    Bopp, Selina E R; Ramachandran, Vandana; Henson, Kerstin; Luzader, Angelina; Lindstrom, Merle; Spooner, Muriel; Steffy, Brian M; Suzuki, Oscar; Janse, Chris; Waters, Andrew P; Zhou, Yingyao; Wiltshire, Tim; Winzeler, Elizabeth A

    2010-05-28

    The genetic background of a patient determines in part if a person develops a mild form of malaria and recovers, or develops a severe form and dies. We have used a mouse model to detect genes involved in the resistance or susceptibility to Plasmodium berghei malaria infection. To this end we first characterized 32 different mouse strains infected with P. berghei and identified survival as the best trait to discriminate between the strains. We found a locus on chromosome 6 by linking the survival phenotypes of the mouse strains to their genetic variations using genome wide analyses such as haplotype associated mapping and the efficient mixed-model for association. This new locus involved in malaria resistance contains only two genes and confirms the importance of Ppar-gamma in malaria infection.

  6. The population structure of Salmonella enterica Enteritidis in Iran analyzed by multiple-locus variable-number tandem repeat analysis.

    PubMed

    Ghaderi, Rainak; Tadayon, Keyvan; Avagyan, Sargis; Khaki, Pejvak; Bidhendi, Soheila Moradi; Forbes, Ken James; Mosavari, Nader; Toroghi, Mohammad Reza; Moosakhani, Farhad; Banihashemi, Reza; Sekhavati, Mohamad; Karimnasab, Nasim

    2013-04-01

    Salmonella enterica Enteritidis is the most frequent etiological agent of salmonellosis in humans and poultry. To understand the genetic diversity of S. Enteritidis in Iran, we examined 69 chicken isolates from 18 broiler farms and six non-epidemic human isolates from six geographically distant provinces by multi-locus variable-number tandem repeat analysis (MLVA). Among SE2, SE3, SE5, SE7, SE8, SENTR4, and SENTR7, only SE5 with four and SENTR7 with two alleles, respectively, proved variable giving estimates of locus genetic diversity of 0.58 and 0. In all, six closely related MLVA profiles were identified among which three were commonly represented by human and chicken isolates. This population homogeneity contrasts with the high diversity at these loci reported elsewhere and is likely a consequence of a single clone of S. Enteritidis distributed across Iran.

  7. Lafora disease is not linked to the Unverricht-Lundborg locus.

    PubMed

    Labauge, P; Beck, C; Bellet, H; Coquillat, G; Vespignani, H; Dulac, O; Gilgenkrantz, S; Dravet, C; Genton, P; Pellissier, J F

    1995-02-27

    Lafora disease and Unverricht-Lundborg disease are two forms of progressive myoclonus epilepsies (PME). Recently the gene for Unverricht-Lundborg disease (EPM1) was mapped to chromosome 21q22.3. Using three highly polymorphic DNA markers (D21S212, PFKL, and D21S171) which flank the EPM1 locus, we performed linkage analysis to investigate whether or not the EPM1 gene is also implicated in Lafora disease. Linkage was excluded in three North-African pedigrees each comprising at least two affected individuals. This result suggests that differential diagnosis of Lafora disease and Unverricht-Lundborg disease may be facilitated by molecular genetic analysis.

  8. The relevance of paternity analysis in Romanian population using the D1S80 locus.

    PubMed

    Ceacăreanu, A C; Ceacăreanu, B

    1999-01-01

    At present, DNA fingerprinting for human identification and paternity testing is a necessary and usual procedure. D1S80 is one of the best known polymorphic loci showing a VNTR, and exhibiting a high heterozygosity. This genetic locus, with a Tsp 509 I polymorphism of its 5' flanking sequence (1, 9), have been successfully amplified from human genomic DNA isolated from blood. The Tsp 509 I polymorphism was detected by restriction after PCR amplification. We tested the relevance of paternity analysis using the D1S80 locus considering the allele frequency distribution characteristic for our country. Paternal and maternal bands were compared with the children's DNA patterns. Our data include a comparison between D1S80 alleles amplified from mother, child and the supposed father for three tested families. This study was the first of this type made in Romania. We concluded a good power of discrimination and exclusion for this locus. It can be used successfully in the case of subtypes with low frequencies, and this is frequent for our population because of the high heterozygosity of D1S80 subtypes in Romanian population. We recommend the D1S80 use for exclusion paternity tests in Romanian population, as a very useful molecular tool, but we also recommend a complete set of molecular markers for confirmation paternity test in the same population.

  9. 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.

  10. Evolution and selection of Rhg1, a copy-number variant nematode-resistance locus

    PubMed Central

    Lee, Tong Geon; Kumar, Indrajit; Diers, Brian W; Hudson, Matthew E

    2015-01-01

    The soybean cyst nematode (SCN) resistance locus Rhg1 is a tandem repeat of a 31.2 kb unit of the soybean genome. Each 31.2-kb unit contains four genes. One allele of Rhg1, Rhg1-b, is responsible for protecting most US soybean production from SCN. Whole-genome sequencing was performed, and PCR assays were developed to investigate allelic variation in sequence and copy number of the Rhg1 locus across a population of soybean germplasm accessions. Four distinct sequences of the 31.2-kb repeat unit were identified, and some Rhg1 alleles carry up to three different types of repeat unit. The total number of copies of the repeat varies from 1 to 10 per haploid genome. Both copy number and sequence of the repeat correlate with the resistance phenotype, and the Rhg1 locus shows strong signatures of selection. Significant linkage disequilibrium in the genome outside the boundaries of the repeat allowed the Rhg1 genotype to be inferred using high-density single nucleotide polymorphism genotyping of 15 996 accessions. Over 860 germplasm accessions were found likely to possess Rhg1 alleles. The regions surrounding the repeat show indications of non-neutral evolution and high genetic variability in populations from different geographic locations, but without evidence of fixation of the resistant genotype. A compelling explanation of these results is that balancing selection is in operation at Rhg1. PMID:25735447

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

    PubMed Central

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

    2009-01-01

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

  12. 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.

  13. The contribution of the DFNB1 locus to neurosensory deafness in a Caucasian population

    SciTech Connect

    Maw, M.A.; Allen-Powell, D.R.; Goodey, R.J.

    1995-09-01

    Classical studies have demonstrated genetic heterogeneity for nonsyndromic autosomal recessive congenital neurosensory deafness, with at least six loci postulated. Linkage analysis in two consanguineous Tunisian kindreds has demonstrated that one such deafness locus, DFNB1, maps near chromosome 13 markers D13S175, D13S143, and D13S115. We tested these markers for cosegregation with deafness in 18 New Zealand and 1 Australian nonconsanguineous kindreds, each of which included at least two siblings with nonsyndromic presumed congenital sensorineural deafness and that had a pedigree structure consistent with autosomal recessive inheritance. When all families were combined, a peak two-point lod score of 2.547 ({theta} = .1) was obtained for D13S175, 0.780 ({theta} = .2) for D13S143, and 0.644 ({theta} = .3) for D13S115. While there was no statistically significant evidence for heterogeneity at any of the three loci tested, nine families showed cosegregation of marker haplotypes with deafness. These observations suggest that the DFNB1 locus may make an important contribution to autosomal recessive neurosensory deafness in a Caucasian population. In the nine cosegregating families, phenotypic variation was observed both within sibships (in four families), which indicates that variable expressivity characterizes some genotypes at the DFNB1 locus, and between generations (in two families), which suggests allelic heterogeneity. 13 refs., 4 figs., 3 tabs.

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

    PubMed Central

    Nagoshi, Rodney N.; Gelbart, William M.

    1987-01-01

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

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

    PubMed

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

    2016-05-13

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

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

    PubMed Central

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

    2016-01-01

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

  17. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.

    PubMed

    Khor, Chiea Chuen; Davila, Sonia; Breunis, Willemijn B; Lee, Yi-Ching; Shimizu, Chisato; Wright, Victoria J; Yeung, Rae S M; Tan, Dennis E K; Sim, Kar Seng; Wang, Jie Jin; Wong, Tien Yin; Pang, Junxiong; Mitchell, Paul; Cimaz, Rolando; Dahdah, Nagib; Cheung, Yiu-Fai; Huang, Guo-Ying; Yang, Wanling; Park, In-Sook; Lee, Jong-Keuk; Wu, Jer-Yuarn; Levin, Michael; Burns, Jane C; Burgner, David; Kuijpers, Taco W; Hibberd, Martin L

    2011-11-13

    Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.

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

    SciTech Connect

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

    1996-04-01

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

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

    PubMed

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

    2010-01-01

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

  20. Genetics Home Reference: FG syndrome

    MedlinePlus

    ... M, Fontes M, Poustka A, Moraine C. A gene for FG syndrome maps in the Xq12-q21.31 region. Am J ... and the p.R961W mutation in the MED12 gene. Am J Med Genet A. 2008 Dec 1;146A(23):3011-7. ... heterogeneity of FG syndrome: a fourth locus (FGS4) maps to Xp11.4-p11.3 in an Italian ...

  1. 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

  2. Acculturation and Health Locus of Control among Mexican American Adolescents.

    ERIC Educational Resources Information Center

    Guinn, Bobby

    1998-01-01

    Health locus of control was investigated across culture of origin (Mexicanism), mainstream culture (Americanism), and bicultural linguistic-acculturation domains among 424 Mexican-American adolescents. Belief in powerful others' external control was the strongest explanation of locus of control in the culture-of-origin domain; internal control was…

  3. 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.

  4. 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…

  5. Metacognition: As a Predictor of One's Academic Locus of Control

    ERIC Educational Resources Information Center

    Arslan, Serhat; Akin, Ahmet

    2014-01-01

    The purpose of this study is to examine the effect of metacognition on one's academic locus of control. The study's sample group consists of 451 university students enrolled in various programs at Sakarya University, Turkey. In this study, the Metacognitive Awareness Inventory and the Academic Locus of Control Scale were used. The correlations and…

  6. 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)

  7. Effects of preferred retinal locus placement on text navigation and development of advantageous trained retinal locus.

    PubMed

    Watson, Gale R; Schuchard, Ronald A; De l'Aune, William R; Watkins, Erica

    2006-01-01

    Sixty readers were evaluated for visual function and text-navigation ability. The visual field and preferred retinal locus (PRL) were measured with a scanning laser ophthalmoscope (SLO). We found significant differences in text-navigation ability based on scotoma and PRL placement. Readers with a PRL to the left of or above a scotoma had significantly less text-navigation abilities. Readers with a PRL to the left of a scotoma tended to misread words with similar beginnings and omit the last word on a line. Readers with a PRL above a scotoma tended to skip a line or reread the same line twice. In a follow-up study, seven subjects with a nonadvantageous PRL quickly developed a trained retinal locus (TRL) during instruction with an SLO. Although the readers developed the TRL in about 15 minutes, they read slower with the TRL than the PRL. This TRL research provides promising pilot data.

  8. Genetic Aspects of Early Childhood Stuttering.

    ERIC Educational Resources Information Center

    Ambrose, Nicoline Grinager; And Others

    1993-01-01

    Analysis of pedigrees from parents of 69 preschool children who stuttered revealed that more male than female relatives ever stuttered but that female subjects who stuttered had more female relatives who ever stuttered than did male subjects. Segregation analyses suggest that transmission of a single major genetic locus increases the liability to…

  9. 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.

  10. Induction of specific-locus mutations in male germ cells of the mouse by acrylamide monomer.

    PubMed

    Russell, L B; Hunsicker, P R; Cacheiro, N L; Generoso, W M

    1991-02-01

    Acrylamide monomer (AA), injected into male mice at the maximum tolerated dose of 5 x 50 mg/kg (24-h intervals), significantly increased the specific-locus mutation rate in certain poststem-cell stages of spermatogenesis, but not in spermatogonial stem cells. Germ-cell stages in which the treatment induced dominant lethals--namely, exposed spermatozoa and late spermatids (number of surviving offspring only 3% and 27%, respectively, of those in concurrent controls)--jointly yielded the highest frequency of specific-locus mutations. AA thus conforms to Pattern 1 in our earlier classification of chemicals according to the spermatogenic stage at which they elicit maximum response (Russell et al., 1990). No specific-locus mutations were observed among 17,112 offspring derived from exposed spermatogonial stem cells, a result which rules out (at the 5% significance level) an induced mutation rate greater than 2.3 times the historical control rate. A sustained high productivity in matings made for several months following week 3 indicates that there is no significant spermatogonial killing and that cell selection is presumably not the explanation for the negative result. On the basis of genetic and/or cytogenetic evidence, the mutations induced postmeiotically by AA were 'large lesions' (multi-locus), while one of 2 recovered from exposure of differentiating spermatogonia is probably a small lesion. An earlier survey of mammalian mutagenesis results led us to conclude that, regardless of the classification of a chemical according to the stage at which it elicits its maximum response, the nature of mutations is determined by the germ-cell stage in which they are induced (Russell et al., 1990). The AA results on lesion size and on distribution of mutations among the loci fit the general pattern.

  11. 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.

  12. Haplotype variation of Glu-D1 locus and the origin of Glu-D1d allele conferring superior end-use qualities in common wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In common wheat (Triticum aestivum, AABBDD), the Glu-D1 locus possesses multiple alleles, with Glu-D1a (coding for 1Dx2 and 1Dy12 subunits) and Glu-D1d (encoding 1Dx5 and 1Dy10 subunits) being intensively used in the genetic improvement of end-use qualities. Here, we studied the molecular variatio...

  13. Putatively novel serotypes and the potential for reduced vaccine effectiveness: capsular locus diversity revealed among 5405 pneumococcal genomes

    PubMed Central

    van Tonder, Andries J.; Bray, James E.; Quirk, Sigríður J.; Haraldsson, Gunnsteinn; Jolley, Keith A.; Maiden, Martin C. J.; Hoffmann, Steen; Bentley, Stephen D.; Haraldsson, Ásgeir; Erlendsdóttir, Helga; Kristinsson, Karl G.; Brueggemann, Angela B.

    2017-01-01

    The pneumococcus is a leading global pathogen and a key virulence factor possessed by the majority of pneumococci is an antigenic polysaccharide capsule (‘serotype’), which is encoded by the capsular (cps) locus. Approximately 100 different serotypes are known, but the extent of sequence diversity within the cps loci of individual serotypes is not well understood. Investigating serotype-specific sequence variation is crucial to the design of sequence-based serotyping methodology, understanding pneumococcal conjugate vaccine (PCV) effectiveness and the design of future PCVs. The availability of large genome datasets makes it possible to assess population-level variation among pneumococcal serotypes and in this study 5405 pneumococcal genomes were used to investigate cps locus diversity among 49 different serotypes. Pneumococci had been recovered between 1916 and 2014 from people of all ages living in 51 countries. Serotypes were deduced bioinformatically, cps locus sequences were extracted and variation was assessed within the cps locus, in the context of pneumococcal genetic lineages. Overall, cps locus sequence diversity varied markedly: low to moderate diversity was revealed among serogroups/types 1, 3, 7, 9, 11 and 22; whereas serogroups/types 6, 19, 23, 14, 15, 18, 33 and 35 displayed high diversity. Putative novel and/or hybrid cps loci were identified among all serogroups/types apart from 1, 3 and 9. This study demonstrated that cps locus sequence diversity varied widely between serogroups/types. Investigation of the biochemical structure of the polysaccharide capsule of major variants, particularly PCV-related serotypes and those that appear to be novel or hybrids, is warranted. PMID:28133541

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

    PubMed Central

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

    2007-01-01

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

  15. Genetic Mapping

    MedlinePlus

    ... Fact Sheets Fact Sheets En Español: Mapeo Genético Genetic Mapping What is genetic mapping? How do researchers ... genetic map? What are genetic markers? What is genetic mapping? Among the main goals of the Human ...

  16. Genetic Counseling

    MedlinePlus

    ... Home > Pregnancy > Before or between pregnancies > Genetic counseling Genetic counseling E-mail to a friend Please fill ... a genetic counselor in your area. What is genetic counseling? Genetic counseling helps you understand how genes , ...

  17. Meeting Abstracts - Annual Meeting 2016.

    PubMed

    2016-04-01

    The AMCP Abstracts program provides a forum through which authors can share their insights and outcomes of advanced managed care practice through publication in AMCP's Journal of Managed Care & Specialty Pharmacy (JMCP). Most of the reviewed and unreviewed abstracts are presented as posters so that interested AMCP meeting attendees can review findings and query authors. The Student/Resident/ Fellow poster presentation (unreviewed) is Wednesday, April 20, 2016, and the Professional poster presentation (reviewed) is Thursday, April 21. The Professional posters will also be displayed on Friday, April 22. The reviewed abstracts are published in the JMCP Meeting Abstracts supplement. The AMCP Managed Care & Specialty Pharmacy Annual Meeting 2016 in San Francisco, California, is expected to attract more than 3,500 managed care pharmacists and other health care professionals who manage and evaluate drug therapies, develop and manage networks, and work with medical managers and information specialists to improve the care of all individuals enrolled in managed care programs. Abstracts were submitted in the following categories: Research Report: describe completed original research on managed care pharmacy services or health care interventions. Examples include (but are not limited to) observational studies using administrative claims, reports of the impact of unique benefit design strategies, and analyses of the effects of innovative administrative or clinical programs. Economic Model: describe models that predict the effect of various benefit design or clinical decisions on a population. For example, an economic model could be used to predict the budget impact of a new pharmaceutical product on a health care system. Solving Problems in Managed Care: describe the specific steps taken to introduce a needed change, develop and implement a new system or program, plan and organize an administrative function, or solve other types of problems in managed care settings. These

  18. Meeting Venus

    NASA Astrophysics Data System (ADS)

    Sterken, Christiaan; Aspaas, Per Pippin

    2013-06-01

    On 2-3 June 2012, the University of Tromsoe hosted a conference about the cultural and scientific history of the transits of Venus. The conference took place in Tromsoe for two very specific reasons. First and foremost, the last transit of Venus of this century lent itself to be observed on the disc of the Midnight Sun in this part of Europe during the night of 5 to 6 June 2012. Second, several Venus transit expeditions in this region were central in the global enterprise of measuring the scale of the solar system in the eighteenth century. The site of the conference was the Nordnorsk Vitensenter (Science Centre of Northern Norway), which is located at the campus of the University of Tromsoe. After the conference, participants were invited to either stay in Tromsoe until the midnight of 5-6 June, or take part in a Venus transit voyage in Finnmark, during which the historical sites Vardoe, Hammerfest, and the North Cape were to be visited. The post-conference program culminated with the participants observing the transit of Venus in or near Tromsoe, Vardoe and even from a plane near Alta. These Proceedings contain a selection of the lectures delivered on 2-3 June 2012, and also a narrative description of