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Sample records for alpha phenotypes linkage

  1. EEG alpha phenotypes: linkage analyses and relation to alcohol dependence in an American Indian community study

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    Phillips Evelyn

    2010-03-01

    Full Text Available Abstract Background Evidence for a high degree of heritability of EEG alpha phenotypes has been demonstrated in twin and family studies in a number of populations. However, information on linkage of this phenotype to specific chromosome locations is still limited. This study's aims were to map loci linked to EEG alpha phenotypes and to determine if there was overlap with loci previously mapped for alcohol dependence in an American Indian community at high risk for substance dependence. Methods Each participant gave a blood sample and completed a structured diagnostic interview using the Semi Structured Assessment for the Genetics of Alcoholism. Bipolar EEGs were collected and spectral power determined in the alpha (7.5-12.0 Hz frequency band for two composite scalp locations previously identified by principal components analyses (bilateral fronto-central and bilateral centro-parietal-occipital. Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 410 members of multiplex families using SOLAR. Results Sixty percent of this study population had a lifetime diagnosis of alcohol dependence. Analyses of multipoint variance component LOD scores, for the EEG alpha power phenotype, revealed two loci that had a LOD score of 3.0 or above for the fronto-central scalp region on chromosomes 1 and 6. Additionally, 4 locations were identified with LOD scores above 2.0 on chromosomes 4, 11, 14, 16 for the fronto-central location and one on chromosome 2 for the centro-parietal-occipital location. Conclusion These results corroborate the importance of regions on chromosome 4 and 6 highlighted in prior segregation studies in this and other populations for alcohol dependence-related phenotypes, as well as other areas that overlap with other substance dependence phenotypes identified in previous linkage studies in other populations. These studies additionally support the construct that EEG alpha recorded from fronto-central scalp areas may

  2. Fine mapping quantitative trait loci under selective phenotyping strategies based on linkage and linkage disequilibrium criteria

    DEFF Research Database (Denmark)

    Ansari-Mahyari, S; Berg, P; Lund, M S

    2009-01-01

    In fine mapping of a large-scale experimental population where collection of phenotypes are very expensive, difficult to record or time-demanding, selective phenotyping could be used to phenotype the most informative individuals. Linkage analyses based sampling criteria (LAC) and linkage disequil......In fine mapping of a large-scale experimental population where collection of phenotypes are very expensive, difficult to record or time-demanding, selective phenotyping could be used to phenotype the most informative individuals. Linkage analyses based sampling criteria (LAC) and linkage...... disequilibrium-based sampling criteria (LDC) for selecting individuals to phenotype are compared to random phenotyping in a quantitative trait loci (QTL) verification experiment using stochastic simulation. Several strategies based on LAC and LDC for selecting the most informative 30%, 40% or 50% of individuals...... for phenotyping to extract maximum power and precision in a QTL fine mapping experiment were developed and assessed. Linkage analyses for the mapping was performed for individuals sampled on LAC within families and combined linkage disequilibrium and linkage analyses was performed for individuals...

  3. The phenotypic difference discards sib-pair QTL linkage information

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    Wright, F.A. [Univ. of California, San Diego, CA (United States)]|[Univ. of Texas, El Paso, TX (United States)

    1997-03-01

    Kruglyak and Lander provide an important synthesis of methods for (IBD) sib-pair linkage mapping, with an emphasis on the use of complete multipoint inheritance information for each sib pair. These procedures are implemented in the computer program MAPMAKER/SIBS, which performs interval mapping for dichotomous and quantitative traits. The authors present three methods for mapping quantitative trait loci (QTLs): a variant of the commonly used Haseman-Elston regression approach, a maximum-likelihood procedure involving variance components, and a rank-based nonparametric procedure. These approaches and related work use the magnitude of the difference in the sibling phenotype values for each sib pair as the observation for analysis. Linkage is detected if siblings sharing more alleles IBD have similar phenotypes (i.e., a small difference in the phenotype values), while siblings sharing fewer alleles IBD have less similar phenotypes. Such techniques have been used to detect linkage for a number of quantitative traits. However, the exclusive reliance on the phenotypic differences may be due in large part to historical inertia. A likelihood argument is presented here to show that, under certain classical assumptions, the phenotypic differences do not contain the full likelihood information for QTL mapping. Furthermore, considerable gains in power to detect linkage can be achieved with an expanded likelihood model. The development here is related to previous work, which incorporates the full set of phenotypic data using likelihood and robust quasi-likelihood methods. The purpose of this letter is not to endorse a particular approach but to spur research in alternative and perhaps more powerful linkage tests. 17 refs.

  4. Markov chain Monte Carlo linkage analysis of a complex qualitative phenotype.

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    Hinrichs, A; Lin, J H; Reich, T; Bierut, L; Suarez, B K

    1999-01-01

    We tested a new computer program, LOKI, that implements a reversible jump Markov chain Monte Carlo (MCMC) technique for segregation and linkage analysis. Our objective was to determine whether this software, designed for use with continuously distributed phenotypes, has any efficacy when applied to the discrete disease states of the simulated data from the Mordor data from GAW Problem 1. Although we were able to identify the genomic location for two of the three quantitative trait loci by repeated application of the software, the MCMC sampler experienced significant mixing problems indicating that the method, as currently formulated in LOKI, was not suitable for the discrete phenotypes in this data set. PMID:10597502

  5. Phenotypic variability in X-linked ocular albinism: Relationship to linkage genotypes

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    Schnur, R.E. [Children`s Hospital of Philadelphia, PA (United States)]|[Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States); Wick, P.A. [Children`s Hospital of Philadelphia, PA (United States); Bailey, C. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States); Rebbeck, T. [Fox Chase Cancer Center, Philadelphia, PA (United States); Weleber, R.G. [Oregon Health Sciences Univ., Portland, OR (United States); Wagstaff, J. [Boston Children`s Hospital, MA (United States); Grix, A.W. [Univ. of California, Davis, CA (United States); Pagon, R.A. [Children`s Hospital and Medical Center, Seattle, WA (United States); Hockey, A. [Princess Margaret Hospital, Perth (Australia); Edwards, M.J. [Newcastle Western Suburbs Hospital, Waratah (Australia)

    1994-09-01

    One hundred nineteen individuals from 11 families with X-linked ocular albinism (OA1) were studied with respect to both their clinical phenotypes and their linkage genotypes. In a four-generation Australian family, two affected males and an obligatory carrier lacked cutaneous melanin macroglobules (MMGs); ocular features were identical to those of Nettleship-Falls OA1. Four other families had more unusual phenotypic features in addition to OA1. All OA1 families were genotyped at DXS16, DXS85, DXS143, STS, and DXS452 and for a CA-repeat polymorphism at the Kallmann syndrome locus (KAL). Separate two-point linkage analyses were performed for the following: group A, six families with biopsy-proved MMGs in at least one affected male; group B, four families whose biopsy status was not known; and group C, OA-9 only (16 samples), the family without MMGs. At the set of loci closest to OA1, there is no clear evidence in our data set for locus heterogeneity between groups A and C or among the four other families with complex phenotypes. Combined multipoint analysis (LINKMAP) in the 11 families and analysis of individual recombination events confirms that the major locus for OA1 resides within the DXS85-DXS143 interval. The authors suggest that more detailed clinical evaluations of OA1 individuals and families should be performed for future correlation with specific mutations in candidate OA1 genes. 29 refs., 5 figs., 4 tabs.

  6. Restriction fragment length polymorphism of ovine casein genes: close linkage between the alpha s1-, alpha s2-, beta- and kappa-casein loci.

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    Leveziel, H; Metenier, L; Guerin, G; Cullen, P; Provot, C; Bertaud, M; Mercier, J C

    1991-01-01

    Restriction fragment length polymorphism (RFLP) of ovine casein genes was investigated. Genomic DNA from 56 rams was digested with 10 restriction endonucleases and Southern blots probed with the four ovine casein cDNAs (alpha s1-, beta-, alpha s2- and kappa-Cn). Five enzymes, namely, BglI, PvuII, RsaI, TaqI and HindIII revealed nine different RFLPs. The inheritance of six of these polymorphisms was studied by segregation analysis of gametes in nine rams' families, and each of them could be related to the existence of alleles at the relevant casein locus. A close linkage between the four ovine casein genes was demonstrated since no recombination within the four pairs of loci examined, alpha s1-beta-Cn, alpha s1-kappa-Cn, beta-kappa-Cn and alpha s2-kappa-Cn, was observed in the progeny of double heterozygous rams. The casein genes are thus clustered in the ovine species as in the case of other mammals.

  7. Mutation in collagen II alpha 1 isoforms delineates Stickler and Wagner syndrome phenotypes

    OpenAIRE

    Tran-Viet, Khanh-Nhat; Soler, Vincent; Quiette, Valencia; POWELL, CALDWELL; Yanovitch, Tammy; Metlapally, Ravikanth; Luo, Xiaoyan; Katsanis, Nicholas; Nading, Erica; Young, Terri L.

    2013-01-01

    Purpose Stickler syndrome is an arthro-ophthalmopathy with phenotypic overlap with Wagner syndrome. The common Stickler syndrome type I is inherited as an autosomal dominant trait, with causal mutations in collagen type II alpha 1 (COL2A1). Wagner syndrome is associated with mutations in versican (VCAN), which encodes for a chondroitin sulfate proteoglycan. A three-generation Caucasian family variably diagnosed with either syndrome was screened for sequence variants in the COL2A1 and VCAN gen...

  8. Subcellular site of synthesis of the N-acetylgalactosamine (alpha 1-0) serine (or threonine) linkage in rat liver

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    Abeijon, C.; Hirschberg, C.B.

    1987-03-25

    We have studied the subcellular site of synthesis of the GalNAc(alpha-1-0) Ser/Thr linkage in rat liver. The specific and total activities of polypeptide:N-acetylgalactosaminyltransferase (using apomucin as exogenous acceptor) were highly enriched in membrane fractions derived from the Golgi apparatus; virtually no activity was detected in membranes from the rough and smooth endoplasmic reticulum. Vesicles of the above organelles (which were sealed and of the same membrane topographical orientation as in vivo) were able to translocate UDP-GalNAc into their lumen in an assay in vitro; the initial translocation rate into Golgi vesicles was 4-6-fold higher than that into vesicles from the rough and smooth endoplasmic reticulum. Translocation of UDP-GalNAc into Golgi vesicles was temperature dependent and saturable with an apparent Km of 8-10 microM. UDP-GalNAc labeled with different radioisotopes in the uridine and sugar was used to determine that the intact sugar nucleotide was being translocated in a reaction coupled to the exit of luminal UMP. Following translocation of UDP-GalNAc, transfer of GalNAc into endogenous macromolecular acceptors was detected in Golgi vesicles and not in those from the rough and smooth endoplasmic reticulum. The above results together with previous studies on the O-xylosylation of the linkage region of proteoglycans strongly suggest that, in rat liver, the bulk of O-glycosylation reactions occur in the Golgi apparatus.

  9. A combined genome-wide linkage and association approach to find susceptibility loci for platelet function phenotypes in European American and African American families with coronary artery disease

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    Wilson Alexander F

    2010-06-01

    Full Text Available Abstract Background The inability of aspirin (ASA to adequately suppress platelet aggregation is associated with future risk of coronary artery disease (CAD. Heritability studies of agonist-induced platelet function phenotypes suggest that genetic variation may be responsible for ASA responsiveness. In this study, we leverage independent information from genome-wide linkage and association data to determine loci controlling platelet phenotypes before and after treatment with ASA. Methods Clinical data on 37 agonist-induced platelet function phenotypes were evaluated before and after a 2-week trial of ASA (81 mg/day in 1231 European American and 846 African American healthy subjects with a family history of premature CAD. Principal component analysis was performed to minimize the number of independent factors underlying the covariance of these various phenotypes. Multi-point sib-pair based linkage analysis was performed using a microsatellite marker set, and single-SNP association tests were performed using markers from the Illumina 1 M genotyping chip from deCODE Genetics, Inc. All analyses were performed separately within each ethnic group. Results Several genomic regions appear to be linked to ASA response factors: a 10 cM region in African Americans on chromosome 5q11.2 had several STRs with suggestive (p-value -4 and significant (p-value -5 linkage to post aspirin platelet response to ADP, and ten additional factors had suggestive evidence for linkage (p-value -4 to thirteen genomic regions. All but one of these factors were aspirin response variables. While the strength of genome-wide SNP association signals for factors showing evidence for linkage is limited, especially at the strict thresholds of genome-wide criteria (N = 9 SNPs for 11 factors, more signals were considered significant when the association signal was weighted by evidence for linkage (N = 30 SNPs. Conclusions Our study supports the hypothesis that platelet phenotypes in

  10. Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II).

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    Loughlin, J; Irven, C; Hardwick, L J; Butcher, S; Walsh, S; Wordsworth, P; Sykes, B

    1995-09-01

    Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective tissue with skin, ligaments and blood vessels being the main sites affected. The commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and is characterized by joint hypermobility, cigarette paper scars, lax skin and excessive bruising. As yet no gene has been linked to EDS II, nor has linkage been established to a specific region of the genome. However, several candidate genes encoding proteins of the extracellular matrix have been excluded. Using an intragenic simple sequence repeat polymorphism, we report linkage of the COL5A1 gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II. A maximum LOD score (Zmax) for linkage of 8.3 at theta = 0.00 was generated for a single large pedigree.

  11. Association and linkage analyses of the alpha and beta genes of the sodium-potassium ATPase with age-related changes in blood pressures

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    Perusse, L.; Deriaz, O.; Dlonne, F.T. [Laval Univ., Quebec (Canada)] [and others

    1994-09-01

    Sodium-potassium-adenosine triphosphatase (Na-K-ATPase), a membrane-bound enzyme responsible for the maintenance of Na{sup +} and K{sup +} gradients in the cell, has been hypothesized to play a role in the etiology of hypertension. To test whether genetic variation in the alpha ({alpha}) and beta ({beta}) genes of the Na-K-ATPase were related to changes in blood pressure with age, systolic (SBP) and diastolic (DBP) blood pressures were measured in 1980 (T1) and 1991 (T2) in 293 members of 74 randomly ascertained families. Changes ({Delta}) between these two time periods (T2-T1) were also computed. Four RFLPs in the {alpha}1, {alpha}2 (exon 1 and exon 21-22) and {beta} genes were identified. Analysis of variance performed in the unrelated parents revealed no significant differences between genotypes at the {alpha}1 and {alpha}2 loci for both {Delta}SBP and {Delta}DBP. However, significant differences between genotypes at the {beta} locus were observed for {Delta}SBP adjusted for age at T1. Linkage analysis of {Delta}SBP and {Delta}DBP with these RFLPs was performed using the sib-pair method. Results revealed a strong linkage (p=.0005) of {Delta}SBP with the RFLP and the {beta} locus, but not with the other RFLPs. No evidence of association or linkage was observed for any of the cross-sectional (T1 or T2) blood pressure values. These results suggest that genetic variation at the {beta} locus of the Na-K-ATPase identified by a PvuII RFLP is related to changes of SBP with age and that this gene could play a role in the development of hypertension.

  12. Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

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    Akira Suzuki

    2012-01-01

    Full Text Available Alpha-fetoprotein-producing carcinoma (AFPC/hepatoid adenocarcinoma (HAC and neuroendocrine carcinoma (NEC are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component.

  13. Physical and linkage mapping of the human and murine genes for the [alpha]1 chain of type IX collagen (COL9A1)

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    Warman, M.L. (Harvard Medical School, Boston, MA (United States) Children' s Hospital/Harvard Medical School, Boston, MA (United States)); Tiller, G.E.; Polumbo, P.A. (Vanderbilt Univ. Medical Center, Nashville, TN (United States)); Seldin, M.F.; Rochelle, J.M. (Duke Univ. Medical Center, Durham, NC (United States)); Knoll, J.H.M.; Cheng, Sou De (Children' s Hospital/Harvard Medical School, Boston, MA (United States)); Olsen, B.R. (Harvard Medical School, Boston, MA (United States))

    1993-09-01

    The IX collagen, a member of the FACIT family of extracellular matrix proteins, is a heterotrimer composed of three genetically distinct [alpha] chains. The cDNAs for the human and mouse [alpha]1(IX) chains have been cloned. In this paper the authors confirm the mapping of the human COL9A1 gene to chromosome 6q12-q13 by fluorescence in situ hybridization utilizing two genomic clones which also contain short tandem repeat polymorphisms. They also report the characterization of these repeats and their incorporation into the chromosome 6 linkage map. The COL9A1 locus shows no recombination with the marker D6Z1 (Z = 27.61 at [theta] = 0) and identifies the most likely locus order of KRAS1P-[D6Z1-COL9A1]-D6S30. In addition, using an interspecific backcross panel, they have mapped murine Col9a1 to mouse chromosome 1. Together with other comparative mapping results, these data suggest that the pericentric region of human chromosome 6 is homologous to the most proximal segment of mouse chromosome 1. These data may facilitate linkage studies with COL9A1 (or col9a1) as a candidate gene for hereditary chondrodysplasias and osteoarthritis. 35 refs., 2 figs., 2 tabs.

  14. Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice

    DEFF Research Database (Denmark)

    Guo, L T; Zhang, X U; Kuang, W;

    2003-01-01

    Deficiency of laminin alpha2 is the cause of one of the most severe muscular dystrophies in humans and other species. It is not yet clear how particular mutations in the laminin alpha2 chain gene affect protein expression, and how abnormal levels or structure of the protein affect disease. Animal...... substantially prevented the muscular dystrophy in these mice. However, dy(W)/dy(W) mice, expressing the human laminin alpha2 under the control of the striated muscle-specific portion of the desmin promoter, still developed muscular dystrophy. This failure to rescue is apparently because of insufficient...... production of laminin alpha2. This study provides additional evidence that the amount of laminin alpha2 is most critical for the prevention of muscular dystrophy. These data may thus be of significance for attempts to treat congenital muscular dystrophy in human patients....

  15. Terminal osseous dysplasia with pigmentary defects (TODPD): Follow-up of the first reported family, characterization of the radiological phenotype, and refinement of the linkage region.

    Science.gov (United States)

    Brunetti-Pierri, Nicola; Lachman, Ralph; Lee, Kwanghyuk; Leal, Suzanne M; Piccolo, Pasquale; Van Den Veyver, Ignatia B; Bacino, Carlos A

    2010-07-01

    Terminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome with distal limb anomalies and pigmentary skin defects. We have previously described this syndrome in several females from a large, four-generation pedigree. The presentation in the affected patients included multiple anomalies, hypertelorism, iris colobomas, punched-out pigmentary abnormalities over the face and scalp, brachydactyly, and digital fibromatosis. The phenotype was highly variable thus suggesting that X-inactivation plays an important role in the expression of the disease. Following our initial description of this condition there have been reports of more cases supporting the initial phenotypic description of this disease. We report on the follow-up of this family at about 10 years from the first evaluation. A detailed clinical follow-up and a review of the skeletal surveys suggests that although the most striking features involves the hands and feet, the skeletal involvement is more generalized and affects many other areas. Our previous linkage analysis has demonstrated mapping to Xq27.3-Xq28. Using a 6,056 SNP array, we have further refined the critical region within the Xq28 region. We have also excluded two candidate genes (FLNA and FAM58A) mapping in the critical region. The identification of the gene responsible for this rare condition will shed light on the molecular pathways leading to the various congenital anomalies of TODPD and will allow a more accurate genetic counseling to the affected individuals.

  16. Mutation Analysis of 16 Mucolipidosis II and III Alpha/Beta Chinese Children Revealed Genotype-Phenotype Correlations

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    Liu, Shuang; Zhang, Weimin; Shi, Huiping; Yao, Fengxia; Wei, Min; Qiu, Zhengqing

    2016-01-01

    Mucolipidosis II and III alpha/beta are autosomal recessive diseases caused by mutations in the GNPTAB gene which encodes the α and β subunits of the N-acetylglucosamine-1-phosphotransferase. Clinically, mucolipidosis II (MLII) is characterized by severe developmental delay, coarse facial features, skeletal deformities, and other systemic involvement. In contrast, MLIII alpha/beta is a much milder disorder, the symptoms of which include progressive joint stiffness, short stature, and scoliosis. To study the relationship between the genotypes and phenotypes of the MLII and MLIII alpha/beta patients, we analyzed the GNPTAB gene in 16 Chinese MLII and MLIII alpha/beta patients. We collected and analyzed the patients’ available clinical data and all showed clinical features typical of MLII or MLIII alpha/beta. Moreover, the activity of several lysosomal enzymes was measured in the plasma and finally the GNPTAB gene was sequenced. We detected 30 mutant alleles out of 32 alleles in our patients. These include 10 new mutations (c.99delC, c.118-1G>A, c.523_524delAAinsG, c.1212C>G, c.2213C>A, c.2345C>T, c.2356C>T, c.2455G>T, c.2821dupA, and c.3136-2A>G) and 5 previously reported mutations (c.1071G>A, c.1090C>T, c.2715+1G>A, c.2550_2554delGAAA, and c.3613C>T). The most frequent mutation was the splicing mutation c.2715+1G>A, which accounted for 28% of the mutations. The majority of the mutations reported in the Chinese patients (57%) were located on exon 13 or in its intronic flanking regions. PMID:27662472

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

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    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...

  18. CRB2 mutations produce a phenotype resembling congenital nephrosis, Finnish type, with cerebral ventriculomegaly and raised alpha-fetoprotein.

    Science.gov (United States)

    Slavotinek, Anne; Kaylor, Julie; Pierce, Heather; Cahr, Michelle; DeWard, Stephanie J; Schneidman-Duhovny, Dina; Alsadah, Adnan; Salem, Fadi; Schmajuk, Gabriela; Mehta, Lakshmi

    2015-01-01

    We report five fetuses and a child from three families who shared a phenotype comprising cerebral ventriculomegaly and echogenic kidneys with histopathological findings of congenital nephrosis. The presenting features were greatly elevated maternal serum alpha-fetoprotein (MSAFP) or amniotic fluid alpha-fetoprotein (AFAFP) levels or abnormalities visualized on ultrasound scan during the second trimester of pregnancy. Exome sequencing revealed deleterious sequence variants in Crumbs, Drosophila, Homolog of, 2 (CRB2) consistent with autosomal-recessive inheritance. Two fetuses with cerebral ventriculomegaly and renal microcysts were compound heterozygotes for p.Asn800Lys and p.Trp759Ter, one fetus with renal microcysts was a compound heterozygote for p.Glu643Ala and p.Asn800Lys, and one child with cerebral ventriculomegaly, periventricular heterotopias, echogenic kidneys, and renal failure was homozygous for p.Arg633Trp in CRB2. Examination of the kidneys in one fetus showed tubular cysts at the corticomedullary junction and diffuse effacement of the epithelial foot processes and microvillous transformation of the renal podocytes, findings that were similar to those reported in congenital nephrotic syndrome, Finnish type, that is caused by mutations in nephrin (NPHS1). Loss of function for crb2b and nphs1 in Danio rerio were previously shown to result in loss of the slit diaphragms of the podocytes, leading to the hypothesis that nephrosis develops from an inability to develop a functional glomerular barrier. We conclude that the phenotype associated with CRB2 mutations is pleiotropic and that the condition is an important consideration in the evaluation of high MSAFP/AFAFP where a renal cause is suspected.

  19. Low voltage alpha EEG phenotype is associated with reduced amplitudes of alpha event-related oscillations, increased cortical phase synchrony, and a low level of response to alcohol.

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    Ehlers, Cindy L; Wills, Derek N; Phillips, Evelyn; Havstad, James

    2015-10-01

    Low voltage EEG (LVEEG) is a heritable phenotype that differs depending on ancestral heritage, yet its impact on brain networks and cognition remain relatively unexplored. In this study we assessed energy and task related phase locking of event-related oscillation (EROs), behavioral responses, measures of IQ and personality, and expected responses to alcohol in a large sample of individuals with LVEEG compared to those with higher voltage variants. Participants (n=762) were recruited from a Native American community and completed a diagnostic interview, the Quick Test, the Subjective High Assessment Scale Expectation Version (SHAS-E) and the Maudsley Personality Inventory. Clinical and spectral analyzed EEGs were collected for determination of the presence of a LVEEG variant. EROs were generated using a facial expression recognition task. Participants with LVEEG (n=451) were significantly more likely to be older, married and have higher degrees of Native American heritage but did not differ in gender, income or education. Individuals with LVEEG were also found to have decreased energy in their alpha EROs, increased phase locking between stimulus trials, and increased phase-locking between cortical brain areas. No significant differences in the cognitive tests, personality variables or alcohol dependence or anxiety diagnoses were found, however, individuals with LVEEG did report a larger number of drinks ever consumed in a 24-h period and a less intense expected response to alcohol. These data suggest that alpha power in the resting EEG is highly associated with energy and cortical connectivity measures generated by event-related stimuli, as well as potentially increased risk for alcohol use. PMID:26151497

  20. HTR3B is associated with alcoholism with antisocial behavior and alpha EEG power--an intermediate phenotype for alcoholism and co-morbid behaviors.

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    Ducci, Francesca; Enoch, Mary-Anne; Yuan, Qiaoping; Shen, Pei-Hong; White, Kenneth V; Hodgkinson, Colin; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

    2009-02-01

    Alcohol use disorders (AUD) with co-morbid antisocial personality disorder (ASPD) have been associated with serotonin (5-HT) dysfunction. 5-HT3 receptors are potentiated by ethanol and appear to modulate reward. 5-HT3 receptor antagonists may be useful in the treatment of early-onset alcoholics with co-morbid ASPD. Low-voltage alpha electroencephalogram (EEG) power, a highly heritable trait, has been associated with both AUD and ASPD. A recent whole genome linkage scan in one of our samples, Plains American Indians (PI), has shown a suggestive linkage peak for alpha power at the 5-HT3R locus. We tested whether genetic variation within the HTR3A and HTR3B genes influences vulnerability to AUD with comorbid ASPD (AUD+ASPD) and moderates alpha power. Our study included three samples: 284 criminal alcoholic Finnish Caucasians and 234 controls; two independent community-ascertained samples with resting EEG recordings: a predominantly Caucasian sample of 191 individuals (Bethesda) and 306 PI. In the Finns, an intronic HTR3B SNP rs3782025 was associated with AUD+ASPD (P=.004). In the Bethesda sample, the same allele predicted lower alpha power (P=7.37e(-5)). Associations between alpha power and two other HTR3B SNPs were also observed among PI (P=.03). One haplotype in the haplotype block at the 3' region of the gene that included rs3782025 was associated with AUD+ASPD in the Finns (P=.02) and with reduced alpha power in the Bethesda population (P=.00009). Another haplotype in this block was associated with alpha power among PI (P=.03). No associations were found for HTR3A. Genetic variation within HTR3B may influence vulnerability to develop AUD with comorbid ASPD. 5-HT3R might contribute to the imbalance between excitation and inhibition that characterize the brain of alcoholics. PMID:19185213

  1. HTR3B is associated with alcoholism with antisocial behavior and alpha EEG power—an intermediate phenotype for alcoholism and co-morbid behaviors

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    Ducci, Francesca; Enoch, Mary-Anne; Yuan, Qiaoping; Shen, Pei-Hong; White, Kenneth V.; Hodgkinson, Colin; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

    2009-01-01

    Alcohol use disorders (AUD) with co-morbid antisocial personality disorder (ASPD) have been associated with serotonin (5-HT) dysfunction. 5-HT3 receptors are potentiated by ethanol and appear to modulate reward. 5-HT3 receptor antagonists may be useful in the treatment of early-onset alcoholics with co-morbid ASPD. Low-voltage alpha electroencephalogram (EEG) power, a highly heritable trait, has been associated with both AUD and ASPD. A recent whole genome linkage scan in one of our samples, Plains American Indians (PI), has shown a suggestive linkage peak for alpha power at the 5-HT3R locus. We tested whether genetic variation within the HTR3A and HTR3B genes influences vulnerability to AUD with comorbid ASPD (AUD + ASPD) and moderates alpha power. Our study included three samples: 284 criminal alcoholic Finnish Caucasians and 234 controls; two independent community-ascertained samples with resting EEG recordings: a predominantly Caucasian sample of 191 individuals (Bethesda) and 306 PI. In the Finns, an intronic HTR3B SNP rs3782025 was associated with AUD + ASPD (P = .004). In the Bethesda sample, the same allele predicted lower alpha power (P = 7.37e-5). Associations between alpha power and two other HTR3B SNPs were also observed among PI (P = .03). One haplotype in the haplotype block at the 3′ region of the gene that included rs3782025 was associated with AUD + ASPD in the Finns (P = .02) and with reduced alpha power in the Bethesda population (P = .00009). Another haplotype in this block was associated with alpha power among PI (P = .03). No associations were found for HTR3A. Genetic variation within HTR3B may influence vulnerability to develop AUD with comorbid ASPD. 5-HT3R might contribute to the imbalance between excitation and inhibition that characterize the brain of alcoholics. PMID:19185213

  2. Identification of distinct human invariant natural killer T-cell response phenotypes to alpha-galactosylceramide

    Directory of Open Access Journals (Sweden)

    Besra Gurdyal S

    2008-12-01

    Full Text Available Abstract Background Human CD1d-restricted, invariant natural killer T cells (iNKT are a unique class of T lymphocytes that recognise glycolipid antigens such as α-galactosylceramide (αGalCer and upon T cell receptor (TCR activation produce both Th1 and Th2 cytokines. iNKT cells expand when cultured in-vitro with αGalCer and interleukin 2 (IL-2 in a CD1d-restricted manner. However, the expansion ratio of human iNKT cells varies between individuals and this has implications for attempts to manipulate this pathway therapeutically. We have studied a panel of twenty five healthy human donors to assess the variability in their in-vitro iNKT cell expansion responses to stimulation with CD1d ligands and investigated some of the factors that may influence this phenomenon. Results Although all donors had comparable numbers of circulating iNKT cells their growth rates in-vitro over 14 days in response to a range of CD1d ligands and IL-2 were highly donor-dependent. Two reproducible donor response patterns of iNKT expansion were seen which we have called 'strong' or 'poor' iNKT responders. Donor response phenotype did not correlate with age, gender, frequency of circulating iNKT, or with the CD1d ligand utilised. Addition of exogenous recombinant human interleukin 4 (IL-4 to 'poor' responder donor cultures significantly increased their iNKT proliferative capacity, but not to levels equivalent to that of 'strong' responder donors. However in 'strong' responder donors, addition of IL-4 to their cultures did not significantly alter the frequency of iNKT cells in the expanded CD3+ population. Conclusion (i in-vitro expansion of human iNKT cells in response to CD1d ligand activation is highly donor variable, (ii two reproducible patterns of donor iNKT expansion were observed, which could be classified into 'strong' and 'poor' responder phenotypes, (iii donor iNKT response phenotypes did not correlate with age, gender, frequency of circulating iNKT cells, or

  3. Overexpression of synphilin-1 promotes clearance of soluble and misfolded alpha-synuclein without restoring the motor phenotype in aged A30P transgenic mice.

    Science.gov (United States)

    Casadei, Nicolas; Pöhler, Anne-Maria; Tomás-Zapico, Cristina; Torres-Peraza, Jesús; Schwedhelm, Ivo; Witz, Annemarie; Zamolo, Irina; De Heer, Raymond; Spruijt, Berry; Noldus, Lucas P J J; Klucken, Jochen; Lucas, José J; Kahle, Philipp J; Krüger, Rejko; Riess, Olaf; Nuber, Silke

    2014-02-01

    Lewy bodies and neurites are the pathological hallmark of Parkinson's disease. These structures are composed of fibrillized and ubiquitinated alpha-synuclein suggesting that impaired protein clearance is an important event in aggregate formation. The A30P mutation is known for its fast oligomerization, but slow fibrillization rate. Despite its toxicity to neurons, mechanisms involved in either clearance or conversion of A30P alpha-synuclein from its soluble state into insoluble fibrils and their effects in vivo are poorly understood. Synphilin-1 is present in Lewy bodies, interacting with alpha-synuclein in vivo and in vitro and promotes its sequestration into aggresomes, which are thought to act as cytoprotective agents facilitating protein degradation. We therefore crossed animals overexpressing A30P alpha-synuclein with synphilin-1 transgenic mice to analyze its impact on aggregation, protein clearance and phenotype progression. We observed that co-expression of synphilin-1 mildly delayed the motor phenotype caused by A30P alpha-synuclein. Additionally, the presence of N- and C-terminal truncated alpha-synuclein species and fibrils were strongly reduced in double-transgenic mice when compared with single-transgenic A30P mice. Insolubility of mutant A30P and formation of aggresomes was still detectable in aged double-transgenic mice, paralleled by an increase of ubiquitinated proteins and high autophagic activity. Hence, this study supports the notion that co-expression of synphilin-1 promotes formation of autophagic-susceptible aggresomes and consecutively the degradation of human A30P alpha-synuclein. Notably, although synphilin-1 overexpression significantly reduced formation of fibrils and astrogliosis in aged animals, a similar phenotype is present in single- and double-transgenic mice suggesting additional neurotoxic processes in disease progression. PMID:24064336

  4. Refractory Classical Hodgkin Lymphoma Presenting with Atypical Cutaneous Involvement and Diagnosis of ZZ Phenotype Alpha-1 Antitrypsin Deficiency

    Directory of Open Access Journals (Sweden)

    Mohamad Khawandanah

    2014-01-01

    Full Text Available Cutaneous Hodgkin lymphoma is a rare condition. Specific neoplastic involvement can be primary (confined to the skin or secondary to systemic involvement (metastatic. Cutaneous involvement by HL usually occurs late in the course and is associated with poor prognosis; however in some cases it can exhibit indolent behavior. Skin involvement with nonspecific cutaneous findings may represent a paraneoplastic syndrome. We describe a case of 46-year-old white male patient presented with rash and lymphadenopathy which led to the diagnosis of stage IVE mixed cellularity classical Hodgkin lymphoma with skin involvement. His disease was refractory to multiple lines of chemotherapy including (1 AVD (doxorubicin/bleomycin/dacarbazine, (2 brentuximab, and (3 bendamustine, he later achieved complete remission with (4 GCD (gemcitabine/carboplatin/dexamethasone salvage regimen. Bleomycin was not given secondary to poor pulmonary function tests. His treatment was complicated after AVD with multiple pneumothoraces which unmasked the diagnosis of ZZ phenotype alpha-1 antitrypsin (ATT deficiency. Simultaneous existence of Hodgkin lymphoma and ATT is rarely reported.

  5. HTR3B is associated with alcoholism with antisocial behavior and alpha EEG power—an intermediate phenotype for alcoholism and co-morbid behaviors

    OpenAIRE

    Ducci, Francesca; Enoch, Mary-Anne; Yuan, Qiaoping; SHEN, PEI-HONG; White, Kenneth V.; Hodgkinson, Colin; Albaugh, Bernard; Virkkunen, Matti; Goldman, David

    2009-01-01

    Alcohol use disorders (AUD) with co-morbid antisocial personality disorder (ASPD) have been associated with serotonin (5-HT) dysfunction. 5-HT3 receptors are potentiated by ethanol and appear to modulate reward. 5-HT3 receptor antagonists may be useful in the treatment of early-onset alcoholics with co-morbid ASPD. Low-voltage alpha electroencephalogram (EEG) power, a highly heritable trait, has been associated with both AUD and ASPD. A recent whole genome linkage scan in one of our samples, ...

  6. Genome-wide linkage scan to identify loci associated with type 2 diabetes and blood lipid phenotypes in the Sikh Diabetes Study.

    Directory of Open Access Journals (Sweden)

    Dharambir K Sanghera

    Full Text Available In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL cholesterol, low-density lipoprotein (LDL cholesterol, very low-density lipoprotein (VLDL cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS. A total of 870 individuals (526 male/344 female from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using S(all statistics (implemented in Merlin did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011 occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016 and 5p15.33 (p = 0.0031 and for LDL cholesterol at 10p11.23 (p = 0.0045. Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance.

  7. Alpha-thalassemia intellectual disability: variable phenotypic expression among males with a recurrent nonsense mutation - c.109C>T (p.R37X).

    Science.gov (United States)

    Basehore, M J; Michaelson-Cohen, R; Levy-Lahad, E; Sismani, C; Bird, L M; Friez, M J; Walsh, T; Abidi, F; Holloway, L; Skinner, C; McGee, S; Alexandrou, A; Syrrou, M; Patsalis, P C; Raymond, G; Wang, T; Schwartz, C E; King, M-C; Stevenson, R E

    2015-05-01

    Alpha-thalassemia intellectual disability, one of the recognizable X-linked disability syndromes, is characterized by short stature, microcephaly, distinctive facies, hypotonic appearance, cardiac and genital anomalies, and marked skewing of X-inactivation in female carriers. With the advent of next generation sequencing, mutations have been identified that result in less severe phenotypes lacking one or more of these phenotypic manifestations. Here we report five unrelated kindreds in which a c.109C>T (p.R37X) mutation segregates with a variable but overall milder phenotype. The distinctive facial appearance of alpha-thalassemia intellectual disability was present in only one of the 18 affected males evaluated beyond the age of puberty, although suggestive facial appearance was present in several during infancy or early childhood. Although the responsible genetic alteration is a nonsense mutation in exon 2 of ATRX, the phenotype appears to be partially rescued by the production of alternative transcripts and/or other molecular mechanisms. PMID:24805811

  8. PGC-1alpha and PGC-1beta have both similar and distinct effects on myofiber switching toward an oxidative phenotype

    DEFF Research Database (Denmark)

    Mortensen, Ole Hartvig; Frandsen, Lis; Schjerling, Peter;

    2006-01-01

    of myotubes, as seen by mRNA downregulation of the immature embryonal and perinatal myosin heavy-chain (MHC) isoforms. PGC-1alpha or PGC-1beta overexpression enhanced mRNA of the slow oxidative-associated MHC isoform MHCIb and downregulated mRNA levels of the fast glycolytic-associated MHC isoforms MHCIIX...... and MHCIIB. Only PGC-1beta overexpression caused an increase in mRNA of the intermediary fast oxidative-associated MHC isoform MHCIIA. PGC-1alpha or PGC-1beta overexpression upregulated GLUT4 mRNA and downregulated myocyte enhancer factor 2C transcription factor mRNA; only PGC-1alpha overexpression caused......Peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta (PGC-1alpha and PGC-1beta) were overexpressed by adenovirus-mediated gene transfer in cultures of primary rat skeletal muscle cells derived from neonatal myoblasts. Effects on muscle fiber type transition and metabolism...

  9. alpha-dl-Difluoromethylornithine, a Specific, Irreversible Inhibitor of Putrescine Biosynthesis, Induces a Phenotype in Tobacco Similar to That Ascribed to the Root-Inducing, Left-Hand Transferred DNA of Agrobacterium rhizogenes.

    Science.gov (United States)

    Burtin, D; Martin-Tanguy, J; Tepfer, D

    1991-02-01

    alpha-dl-Difluoromethylarginine (DFMA) and alpha-dl-difluoromethylornithine (DFMO), specific irreversible inhibitors of putrescine biosynthesis were applied to Nicotiana tabacum var. Xanthi nc during floral induction. DFMO, but not DFMA, induced a phenotype in tobacco that resembles the transformed phenotype attributed to the root-inducing, left-hand, transferred DNA of Agrobacterium rhizogenes, including wrinkled leaves, shortened internodes, reduced apical dominance, and retarded flowering. Similar treatment of transformed plants (T phenotype) accentuated their phenotypic abnormalities. Cyclohexylammonium and methylglyoxal bis (guanylhydrazone), inhibitors of spermidine and spermine biosynthesis, produced reproductive abnormalities, but did not clearly mimic the transformed phenotype. This work strengthens the previously reported correlation between the degree of expression of the transformed phenotype due to the root-inducing, left-hand, transferred DNA and inhibition of polyamine accumulation, strongly suggesting that genes carried by the root-inducing, transferred DNA may act through interference with polyamine production via the ornithine pathway.

  10. Further evidence for clustering of human GABA[sub A] receptor subunit genes: Localization of the [alpha][sub 6]-subunit gene (GABRA6) to distal chromosome 5q by linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, A.A.; Kamphuis, W.; Darlison, M.G. (MRC Molecular Neurobiology Unit, Cambride (United Kingdom)); Bailey, M.E.S.; Johnson, K.J. (Charing Cross and Westminster Medical School, London (United Kingdom)); Riley, B.P. (St. Mary' s Hospital Medical School, London (United Kingdom)); Siciliano, M.J. (Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States))

    1994-03-15

    GABA[sub A] receptors are hetero-oligomeric ion-channel complexes that are composed of combinations of [alpha], [beta], [gamma], and [delta] subunits and play a major role in inhibitory neurotransmission in the mammalian brain. The authors report here a microsatellite polymorphism within the human [alpha][sub 6]-subunit gene (GABRA6). Mapping of this marker in a human-hamster hybrid cell-line panel and typing of the repeat in the Centre d'Etude du Polymorphisme Humain (CEPH) reference families enabled the localization of this gene to chromosome 5q and established its linkage to the GABA[sub A] receptor [alpha][sub 1]-subunit gene (GA-BRA1) with a maximum lod score (Z[sub max]) of 39.87 at a [theta] of 0.069 (males) and 0.100 (females). These results reveal the clustering of GABRA6, GABRA1, and the GABA[sub A] receptor [gamma][sub 2]-subunit gene (GABRG2) on distal chromosome 5q. 17 refs., 1 fig., 1 tab.

  11. Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: A systems biology based approach

    Science.gov (United States)

    Silveira, Alexandra C.; Morrison, Margaux A.; Ji, Fei; Xu, Haiyan; Reinecke, James B.; Adams, Scott M.; Arneberg, Trevor M.; Janssian, Maria; Lee, Joo-Eun; Yuan, Yang; Schaumberg, Debra A.; Kotoula, Maria G.; Tsironi, Evangeline E.; Tsiloulis, Aristoteles N.; Chatzoulis, Dimitrios Z.; Miller, Joan W.; Kim, Ivana K.; Hageman, Gregory H.; Farrer, Lindsay A.; Haider, Neena B.; DeAngelis, Margaret M.

    2009-01-01

    To identify novel genes and pathways associated with AMD, we performed microarray gene expression and linkage analysis which implicated the candidate gene, retinoic acid receptor-related orphan receptor alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide polymorphisms (SNPs) in a family-based cohort, followed by replication in an unrelated case-control cohort, demonstrated that SNPs and haplotypes located in intron 1 were significantly associated with neovascular AMD risk in both cohorts. This is the first report demonstrating a possible role for RORA, a receptor for cholesterol, in the pathophysiology of AMD. Moreover, we found a significant interaction between RORA and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD pathophysiology. PMID:19786043

  12. Hybrid reuteransucrase enzymes reveal regions important for glucosidic linkage specificity and the transglucosylation/hydrolysis ratio

    NARCIS (Netherlands)

    Kralj, Slavko; van Leeuwen, Sander S.; Valk, Vincent; Eeuwema, Wieger; Kamerling, Johannis P.; Dijkhuizen, Lubbert

    2008-01-01

    The reuteransucrase enzymes of Lactobacillus reuteri strain 121 (GTFA) and L. reuteri strain ATCC 55730 (GTFO) convert sucrose into alpha-d-glucans (labelled reuterans) with mainly alpha-(1 -> 4) glucosidic linkages (50% and 70%, respectively), plus alpha-(1 -> 6) linkages. In the present study, we

  13. Robust Group Linkage

    OpenAIRE

    Li, Pei; Dong, Xin Luna; Guo, Songtao; Maurino, Andrea; Srivastava, Divesh

    2015-01-01

    We study the problem of group linkage: linking records that refer to entities in the same group. Applications for group linkage include finding businesses in the same chain, finding conference attendees from the same affiliation, finding players from the same team, etc. Group linkage faces challenges not present for traditional record linkage. First, although different members in the same group can share some similar global values of an attribute, they represent different entities so can also...

  14. Phenotypic consequences of deletion of the {gamma}{sub 3}, {alpha}{sub 5}, or {beta}{sub 3} subunit of the type A {gamma}-aminobutyric acid receptor in mice

    Energy Technology Data Exchange (ETDEWEB)

    Culia, C.T.; Stubbs, L.J.; Montgomery, C.S.; Russell, L.B.; Rinchik, E.M. [Oak Ridge National Lab., TN (United States)

    1994-03-29

    Three genes (Gabrg3, Gabra5, and Gabrb3) encoding the {gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3} subunits of the type A {gamma}-aminobutyric acid receptor, respectively, are known to map near the pink-eyed dilution (p) locus in mouse chromosome 7. This region shares homology with a segment of human chromosome 15 that is implicated in Angelman syndrome, an inherited neurobehavioral disorder. By mapping Gabrg3-Gabra5-Gabrb3-telomere. Like Gabrb3, neither the Gabra5 nor Gabrg3 gene is functionally imprinted in adult mouse brain. Mice deleted for all three subunits die at birth with a cleft palate, although there are rare survivors ({approximately} 5%) that do not have a cleft palate but do exhibit a neurological abnormality characterized by tremor, jerky gait, and runtiness. The authors have previously suggested that deficiency of the {beta}{sub 3} subunit may be responsible for the clefting defect. Most notably, however, in this report they describe mice carrying two overlapping, complementing p deletions that fail to express the {gamma}{sub 3} transcript, as well as mice from another line that express neither the {gamma}{sub 3} nor {alpha}{sub 5} transcripts. Surprisingly, mice from both of these lines are phenotypically normal and do not exhibit any of the neurological symptoms characteristic of the rare survivors that are deleted for all three ({gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3}) subunits. These mice therefore provide a whole-organism type A {gamma}-aminobutyric-acid receptor background that is devoid of any receptor subtypes that normally contain the {gamma}{sub 3} and/or {alpha}{sub 5} subunits. The absence of an overt neurological phenotype in mice lacking the {gamma}{sub 3} and/or {alpha}{sub 5} subunits also suggests that mutations in these genes are unlikely to provide useful animal models for Angelman syndrome in humans.

  15. Genome-wide linkage analysis of malaria infection intensity and mild disease.

    Directory of Open Access Journals (Sweden)

    Christian Timmann

    2007-03-01

    Full Text Available Although balancing selection with the sickle-cell trait and other red blood cell disorders has emphasized the interaction between malaria and human genetics, no systematic approach has so far been undertaken towards a comprehensive search for human genome variants influencing malaria. By screening 2,551 families in rural Ghana, West Africa, 108 nuclear families were identified who were exposed to hyperendemic malaria transmission and were homozygous wild-type for the established malaria resistance factors of hemoglobin (HbS, HbC, alpha(+ thalassemia, and glucose-6-phosphate-dehydrogenase deficiency. Of these families, 392 siblings aged 0.5-11 y were characterized for malaria susceptibility by closely monitoring parasite counts, malaria fever episodes, and anemia over 8 mo. An autosome-wide linkage analysis based on 10,000 single-nucleotide polymorphisms was conducted in 68 selected families including 241 siblings forming 330 sib pairs. Several regions were identified which showed evidence for linkage to the parasitological and clinical phenotypes studied, among them a prominent signal on Chromosome 10p15 obtained with malaria fever episodes (asymptotic z score = 4.37, empirical p-value = 4.0 x 10(-5, locus-specific heritability of 37.7%; 95% confidence interval, 15.7%-59.7%. The identification of genetic variants underlying the linkage signals may reveal as yet unrecognized pathways influencing human resistance to malaria.

  16. Frequency of alpha- and beta-haemolysin in Staphylococcus aureus of bovine and human origin - A comparison between pheno- and genotype and variation in phenotypic expression

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller; Larsen, H.D.; Eriksen, N.H.R.;

    1999-01-01

    isolates and 24% of the septicaemia isolates did so. No change in expression of haemolysins could be observed after subcultivation of bovine isolates in human blood and milk. After 5 to 10 subcultures in bovine blood and 1 to 4 in bovine milk, 9 of 10 human isolates originally phenotypically beta......-haemolysin negative initiated the expression of beta-haemolysin. This study showed that a larger proportion of S. aureus of bovine origin carry the beta-haemolysin gene compared to isolates from humans. Furthermore, a larger number of the isolates of bovine origin carrying the beta-haemolysin gene express this gene...... phenotypically compared to isolates of human origin....

  17. Hybrid reuteransucrase enzymes reveal regions important for glucosidic linkage specificity and the transglucosylation/hydrolysis ratio

    OpenAIRE

    Kralj, S.; van Leeuwen, S.S.; Valk, Vincent; Eeuwema, W.; Kamerling, J P; Dijkhuizen, L.

    2008-01-01

    The reuteransucrase enzymes of Lactobacillus reuteri strain 121 (GTFA) and L. reuteri strain ATCC 55730 (GTFO) convert sucrose into alpha-d-glucans (labelled reuterans) with mainly alpha-(1 -> 4) glucosidic linkages (50% and 70%, respectively), plus alpha-(1 -> 6) linkages. In the present study, we report a detailed analysis of various hybrid GTFA/O enzymes, resulting in the identification of specific regions in the N-termini of the catalytic domains of these proteins as the main determinants...

  18. Data Mining Applied to Linkage Disequilibrium Mapping

    OpenAIRE

    Toivonen, H T T; Onkamo, P.; Vasko, K; Ollikainen, V; Sevon, P; Mannila, H.; Herr, M; Kere, J

    2000-01-01

    We introduce a new method for linkage disequilibrium mapping: haplotype pattern mining (HPM). The method, inspired by data mining methods, is based on discovery of recurrent patterns. We define a class of useful haplotype patterns in genetic case-control data and use the algorithm for finding disease-associated haplotypes. The haplotypes are ordered by their strength of association with the phenotype, and all haplotypes exceeding a given threshold level are used for prediction of disease susc...

  19. Quantitative linkage genome scan for atopy in a large collection of Caucasian families

    DEFF Research Database (Denmark)

    Webb, BT; van den Oord, E; Akkari, A;

    2007-01-01

    Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early...... report represents one of the biggest genome scans so far reported for asthma related phenotypes. This study also demonstrates the utility of increased sample sizes and quantitative phenotypes in linkage analysis of complex disorders....

  20. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

    Perri, Alessandra; Andersson, Ulf; Nell, Phillip C.;

    competition and subsidiary capabilities. Our theoretical development and the results from the analysis document a far more complex and dynamic relationship between levels of competition and MNCs’ local participation in knowledge intensive activities, i.e. learning and spillovers, than previous studies do. We...... find a curvilinear relationship between the extent of competitive pressure and the quality of local linkages confirming our argument of a trade-off between learning prospects and spillover risks. Furthermore, the level of subsidiary capabilities moderates this relationship.......This paper investigates local vertical linkages of foreign subsidiaries and the dual role of such linkages as conduits for learning as well as potential channels for spillovers to competitors. On the basis of data from 97 subsidiaries, we analyze the quality of such linkages under varying levels of...

  1. Distribution of alpha-2-HS-glycoprotein (AHSG) phenotypes in Cabo Verde (west Africa): description of a new allele, AHSG*32.

    Science.gov (United States)

    Caeiro, J L; Parra, E J; Yuasa, I; Teixeira, C; Llano, C

    1994-04-01

    The genetic polymorphism of alpha-2-HS-glycoprotein (AHSG) was studied in the population of Cabo Verde (West Africa), using isoelectric focusing in polyacrylamide gels followed by immunofixation-silver stain. AHSG frequencies are reported for the first time in a subsaharan African population. In addition to the common variants, AHSG 1 and AHSG 2, five AHSG variants were observed, including a new variant, tentatively designated AHSG 32. The allele frequencies were, AHSG*1: 0.7289, AHSG*2: 0.2111, AHSG*10: 0.0276, AHSG*3: 0.0162, AHSG*11: 0.0081, AHSG*22: 0.0065, AHSG*32:0.0016. PMID:7619771

  2. Topology of randon linkages

    OpenAIRE

    Farber, Michael

    2007-01-01

    Betti numbers of configuration spaces of mechanical linkages (known also as polygon spaces) depend on a large number of parameters -- the lengths of the bars of the linkage. Motivated by applications in topological robotics, statistical shape theory and molecular biology, we view these lengths as random variables and study asymptotic values of the average Betti numbers as the number of links n tends to infinity. We establish a surprising fact that for a reasonably ample class of sequences of ...

  3. Structure and apoprotein linkages of phycourobilin.

    Science.gov (United States)

    Killilea, S D; O'Carra, P

    1985-03-15

    R-Phycoerythrin contains two covalently bound bilin prosthetic groups, phycoerythrobilin and phycourobilin. The two chromophore types were separated as their peptide-bound derivatives by subjecting tryptic digests of R-phycoerythrin to adsorption chromatography on Sephadex G-25. The structure and apoprotein linkages of the bound phycoerythrobilin were found to be identical with those previously reported for this phycobilin [Killilea, O'Carra & Murphy (1980) Biochem. J. 187, 311-320]. Phycourobilin is a tetrapyrrole, containing no oxo bridges and has the same order of side chains as IX alpha bilins. The chromophore is linked to the peptide through two and possibly three of its pyrrole rings. One linkage possibly consists of an ester bond between the hydroxy group of a serine residue and the propionic acid side chain of one of the inner rings. The second linkage is a labile thioether bond between a cysteine residue and the C2 side chain of pyrrole ring A. The third linkage is a stable thioether bond between a cysteine residue and the alpha-carbon atom of the C2 side chain of pyrrole ring D. Ring D is unsaturated and is attached to ring C through a saturated carbon bridge. Rings B and C have a conjugated system of five bonds, as found in other urobilinoid pigments. Ring A is attached to ring B via a saturated carbon bridge. Both of the alpha-positions of ring A are in the reduced state, but the ring does contain an unsaturated centre (probably a double bond between the beta-carbon and the ring nitrogen atom). The presence of this double bond and its isomerization into the bridge position between rings A and B would explain the extension of the conjugated system of phycourobilin to that of a phycoerythrobilinoid/rhodenoid pigment in acid or alkali. PMID:3838665

  4. Model-free linkage analysis of a binary trait.

    Science.gov (United States)

    Xu, Wei; Bull, Shelley B; Mirea, Lucia; Greenwood, Celia M T

    2012-01-01

    Genetic linkage analysis aims to detect chromosomal regions containing genes that influence risk of specific inherited diseases. The presence of linkage is indicated when a disease or trait cosegregates through the families with genetic markers at a particular region of the genome. Two main types of genetic linkage analysis are in common use, namely model-based linkage analysis and model-free linkage analysis. In this chapter, we focus solely on the latter type and specifically on binary traits or phenotypes, such as the presence or absence of a specific disease. Model-free linkage analysis is based on allele-sharing, where patterns of genetic similarity among affected relatives are compared to chance expectations. Because the model-free methods do not require the specification of the inheritance parameters of a genetic model, they are preferred by many researchers at early stages in the study of a complex disease. We introduce the history of model-free linkage analysis in Subheading 1. Table 1 describes a standard model-free linkage analysis workflow. We describe three popular model-free linkage analysis methods, the nonparametric linkage (NPL) statistic, the affected sib-pair (ASP) likelihood ratio test, and a likelihood approach for pedigrees. The theory behind each linkage test is described in this section, together with a simple example of the relevant calculations. Table 4 provides a summary of popular genetic analysis software packages that implement model-free linkage models. In Subheading 2, we work through the methods on a rich example providing sample software code and output. Subheading 3 contains notes with additional details on various topics that may need further consideration during analysis.

  5. A national population-based e-cohort of people with psychosis (PsyCymru) linking prospectively ascertained phenotypically rich and genetic data to routinely collected records: overview, recruitment and linkage.

    Science.gov (United States)

    Lloyd, Keith; McGregor, Joanna; John, Ann; Craddock, Nick; Walters, James T; Linden, David; Jones, Ian; Bentall, Richard; Lyons, Ronan A; Ford, David V; Owen, Michael J

    2015-08-01

    PsyCymru was initially established as a proof of concept to investigate the feasibility of linking a prospectively ascertained, well-characterised (linked clinical cohort) of people with psychosis in Wales, UK with large amounts of anonymised routinely collected health record data. We are now additionally linking genetic data. PsyCymru aims to create a research platform and infrastructure for psychosis research in Wales by the establishment of two cohorts. The first is a well characterised clinically-assessed cohort of 490 individuals aged 16 and over, including genetic data. Consented individuals underwent a structured interview using a series of well-validated questionnaires and gave blood for the purpose of DNA extraction for sequencing and candidate gene identification. This data was linked to routinely collected health and social datasets with identity encryption used to protect privacy. The second is a much larger (12,097 individuals) but less well characterised population-based e-cohort of prevalent psychosis cases created using a previously validated algorithm applied to anonymised routine data. Both cohorts can be tracked prospectively and retrospectively using anonymised routinely collected electronic health and administrative data in the Secure Anonymised Information Linkage (SAIL) databank. This unique platform pools data together from multiple sources; linking clinical, psychological, biological, genetic and health care factors to address a wide variety of research questions. This resource will continue to expand over the coming years in size, breadth and depth of data, with continued recruitment and additional measures planned. PMID:26139629

  6. Levels of alpha-toxin correlate with distinct phenotypic response profiles of blood mononuclear cells and with agr background of community-associated Staphylococcus aureus isolates.

    Science.gov (United States)

    Mairpady Shambat, Srikanth; Haggar, Axana; Vandenesch, Francois; Lina, Gerard; van Wamel, Willem J B; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2014-01-01

    Epidemiological studies of Staphylococcus aureus have shown a relation between certain clones and the presence of specific virulence genes, but how this translates into virulence-associated functional responses is not fully elucidated. Here we addressed this issue by analyses of community-acquired S. aureus strains characterized with respect to antibiotic resistance, ST types, agr types, and virulence gene profiles. Supernatants containing exotoxins were prepared from overnight bacterial cultures, and tested in proliferation assays using human peripheral blood mononuclear cells (PBMC). The strains displayed stable phenotypic response profiles, defined by either a proliferative or cytotoxic response. Although, virtually all strains elicited superantigen-mediated proliferative responses, the strains with a cytotoxic profile induced proliferation only in cultures with the most diluted supernatants. This indicated that the superantigen-response was masked by a cytotoxic effect which was also confirmed by flow cytometry analysis. The cytotoxic supernatants contained significantly higher levels of α-toxin than did the proliferative supernatants. Addition of α-toxin to supernatants characterized as proliferative switched the response into cytotoxic profiles. In contrast, no effect of Panton Valentine Leukocidin, δ-toxin or phenol soluble modulin α-3 was noted in the proliferative assay. Furthermore, a significant association between agr type and phenotypic profile was found, where agrII and agrIII strains had predominantly a proliferative profile whereas agrI and IV strains had a predominantly cytotoxic profile. The differential response profiles associated with specific S. aureus strains with varying toxin production could possibly have an impact on disease manifestations, and as such may reflect specific pathotypes.

  7. The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

    Science.gov (United States)

    Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P.; Viana-Baptista, Miguel; Gomes, António Caldeira; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C.; Oliveira, João Paulo

    2015-01-01

    Summary Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue – GLA p.(Arg118Cys) –, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands’ close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease, since the allelic frequency in stroke patients was 0.0087 (p=0.0185 vs the general population). The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for “rare” condition. PMID:25468652

  8. Relationship of genetically transmitted alpha EEG traits to anxiety disorders and alcoholism

    Energy Technology Data Exchange (ETDEWEB)

    Enoch, M.A.; Rohrbaugh, W.; Harris, C.R. [Washington School of Medicine, St. Louis, MO (United States)] [and others

    1995-10-09

    We tested the hypothesis that a heritable EEG trait, the low voltage alpha (LV), is associated with psychiatric disorders. Modest to moderate evidence for genetic linkage of both panic disorder and the low voltage alpha trait to the same region of chromosome 20q has recently been reported, raising the issue of whether there is a phenotypic correlation between these traits. A total of 124 subjects including 50 unrelated index subjects and 74 relatives were studied. Alpha EEG power was measured and EEG phenotypes were impressionistically classified. Subjects were psychiatrically interviewed using the SADS-L and blind-rated by RDC criteria. Alcoholics were four times more likely to be LV (including so-called borderline low voltage alpha) than were nonalcoholic, nonanxious subjects. Alcoholics with anxiety disorder are 10 times more likely to be LV. However, alcoholics without anxiety disorder were similar to nonalcoholics in alpha power. An anxiety disorder (panic disorder, phobia, or generalized anxiety) was found in 14/17 LV subjects as compared to 34/101 of the rest of the sample (P < 0.01). Support for these observations was found in the unrelated index subjects in whom no traits would be shared by familial clustering. Lower alpha power in anxiety disorders was not state-dependent, as indicated by the Spielberger Anxiety Scale. Familial covariance of alpha power was 0.25 (P < 0.01). These findings indicate there may be a shared factor underlying the transmissible low voltage alpha EEG variant and vulnerability to anxiety disorders with associated alcoholism. This factor is apparently not rare, because LV was found in approximately 10% of unrelated index subjects and 5% of subjects free of alcoholism and anxiety disorders. 43 refs., 1 fig., 3 tabs.

  9. A Linkage Learning Genetic Algorithm with Linkage Matrix

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The goal of linkage learning, or building block identification, is the creation of a more effective Genetic Algorithm (GA). This paper proposes a new Linkage Learning Genetic Algorithms, named m-LLGA. With the linkage learning module and the linkage-based genetic operation, m-LLGA is not only able to learn and record the linkage information among genes without any prior knowledge of the function being optimized. It also can use the linkage information stored in the linkage matrix to guide the selection of crossover point. The preliminary experiments on two kinds of bounded difficulty problems and a TSP problem validated the performance of m-LLGA. The m-LLGA learns the linkage of different building blocks parallel and therefore solves these problems effectively; it can also reasonably reduce the probability of building blocks being disrupted by crossover at the same time give attention to getting away from local minimum.

  10. Cosmopolitan linkage disequilibrium maps

    Directory of Open Access Journals (Sweden)

    Gibson Jane

    2005-03-01

    Full Text Available Abstract Linkage maps have been invaluable for the positional cloning of many genes involved in severe human diseases. Standard genetic linkage maps have been constructed for this purpose from the Centre d'Etude du Polymorphisme Humain and other panels, and have been widely used. Now that attention has shifted towards identifying genes predisposing to common disorders using linkage disequilibrium (LD and maps of single nucleotide polymorphisms (SNPs, it is of interest to consider a standard LD map which is somewhat analogous to the corresponding map for linkage. We have constructed and evaluated a cosmopolitan LD map by combining samples from a small number of populations using published data from a 10-megabase region on chromosome 20. In support of a pilot study, which examined a number of small genomic regions with a lower density of markers, we have found that a cosmopolitan map, which serves all populations when appropriately scaled, recovers 91 to 95 per cent of the information within population-specific maps. Recombination hot spots appear to have a dominant role in shaping patterns of LD. The success of the cosmopolitan map might be attributed to the co-localisation of hot spots in all populations. Although there must be finer scale differences between populations due to other processes (mutation, drift, selection, the results suggest that a whole-genome standard LD map would indeed be a useful resource for disease gene mapping.

  11. Quantitative linkage genome scan for atopy in a large collection of Caucasian families

    DEFF Research Database (Denmark)

    Webb, BT; van den Oord, E; Akkari, A;

    2007-01-01

    Quantitative phenotypes correlated with a complex disorder offer increased power to detect linkage in comparison to affected-unaffected classifications. Asthma is a complex disorder characterized by periods of bronchial obstruction and increased bronchial hyper reactivity. In childhood and early ...

  12. Hybrid reuteransucrase enzymes reveal regions important for glucosidic linkage specificity and the transglucosylation/hydrolysis ratio.

    Science.gov (United States)

    Kralj, Slavko; van Leeuwen, Sander S; Valk, Vincent; Eeuwema, Wieger; Kamerling, Johannis P; Dijkhuizen, Lubbert

    2008-12-01

    The reuteransucrase enzymes of Lactobacillus reuteri strain 121 (GTFA) and L. reuteri strain ATCC 55730 (GTFO) convert sucrose into alpha-d-glucans (labelled reuterans) with mainly alpha-(1-->4) glucosidic linkages (50% and 70%, respectively), plus alpha-(1-->6) linkages. In the present study, we report a detailed analysis of various hybrid GTFA/O enzymes, resulting in the identification of specific regions in the N-termini of the catalytic domains of these proteins as the main determinants of glucosidic linkage specificity. These regions were divided into three equal parts (A1-3; O1-3), and used to construct six additional GTFA/O hybrids. All hybrid enzymes were able to synthesize alpha-glucans from sucrose, and oligosaccharides from sucrose plus maltose or isomaltose as acceptor substrates. Interestingly, not only the A2/O2 regions, with the three catalytic residues, affect glucosidic linkage specificity, but also the upstream A1/O1 regions make a strong contribution. Some GTFO derived hybrid/mutant enzymes displayed strongly increased transglucosylation/hydrolysis activity ratios. The reduced sucrose hydrolysis allowed the much improved conversion of sucrose into oligo- and polysaccharide products. Thus, the glucosidic linkage specificity and transglucosylation/hydrolysis ratios of reuteransucrase enzymes can be manipulated in a relatively simple manner. This engineering approach has yielded clear changes in oligosaccharide product profiles, as well as a range of novel reuteran products differing in alpha-(1-->4) and alpha-(1-->6) linkage ratios. PMID:19016850

  13. Equivalent Linkages of Compressor Mechanisms

    OpenAIRE

    Bukac, Hubert

    2014-01-01

    Frequently, the dynamics of a compressor’s mechanism can be simplified and better understood by analyzing compressor’s equivalent linkage. Although the equivalent linkage of a reciprocating piston compressor is well known, the equivalent linkages of other types of compressors are not. For example, it is not well understood that the equivalent linkage of a rolling piston compressor is also the same slider-crank mechanism as the one of a reciprocating piston compressor. The difference between r...

  14. The first-generation Daphnia magna linkage map

    Directory of Open Access Journals (Sweden)

    De Meester Luc

    2010-09-01

    Full Text Available Abstract Background Daphnia magna is a well-established model species in ecotoxicology, ecology and evolution. Several new genomics tools are presently under development for this species; among them, a linkage map is a first requirement for estimating the genetic background of phenotypic traits in quantitative trait loci (QTL studies and is also very useful in assembling the genome. It also enables comparative studies between D. magna and D. pulex, for which a linkage map already exists. Results Here we describe the first genetic linkage map of D. magna. We generated 214 F2 (intercross clonal lines as the foundation of the linkage analysis. The linkage map itself is based on 109 microsatellite markers, which produced ten major linkage groups ranging in size from 31.1 cM to 288.5 cM. The total size of this linkage map extends to 1211.6 Kosambi cM, and the average interval for the markers within linkage groups is 15.1 cM. The F2 clones can be used to map QTLs for traits that differ between the parental clones. We successfully mapped the location of two loci with infertility alleles, one inherited from the paternal clone (Iinb1 and the other from the maternal clone (Xinb3. Conclusions The D. magna linkage map presented here provides extensive coverage of the genome and a given density of markers that enable us to detect QTLs of moderate to strong effects. It is similar in size to the linkage map of D. pulex.

  15. Coulomb Control of Polygonal Linkages

    NARCIS (Netherlands)

    Khimshiashvili, Giorgi N.; Panina, Gaiane Yu; Siersma, Dirk

    2014-01-01

    Equilibria of polygonal linkage with respect to Coulomb potential of point charges placed at the vertices of linkage are considered. It is proved that any convex configuration of a quadrilateral linkage is the point of global minimum of Coulomb potential for appropriate values of charges of vertices

  16. Coefficient Alpha

    OpenAIRE

    Panayiotis Panayides

    2013-01-01

    Heavy reliance on Cronbach’s alpha has been standard practice in many validation studies. However, there seem to be two misconceptions about the interpretation of alpha. First, alpha is mistakenly considered as an indication of unidimensionality and second, that the higher the value of alpha the better. The aim of this study is to clarify these misconceptions with the use of real data from the educational setting. Results showed that high alpha values can be obtained in multidimensional scale...

  17. A Formalization of Linkage Analysis

    DEFF Research Database (Denmark)

    Ingolfsdottir, Anna; Christensen, A.I.; Hansen, Jens A.;

    In this report a formalization of genetic linkage analysis is introduced. Linkage analysis is a computationally hard biomathematical method, which purpose is to locate genes on the human genome. It is rooted in the new area of bioinformatics and no formalization of the method has previously been ...

  18. Generation of a Restriction Fragment Length Polymorphism Linkage Map for Toxoplasma Gondii

    Science.gov (United States)

    Sibley, L. D.; LeBlanc, A. J.; Pfefferkorn, E. R.; Boothroyd, J. C.

    1992-01-01

    We have constructed a genetic linkage map for the parasitic protozoan, Toxoplasma gondii, using randomly selected low copy number DNA markers that define restriction fragment length polymorphisms (RFLPs). The inheritance patterns of 64 RFLP markers and two phenotypic markers were analyzed among 19 recombinant haploid progeny selected from two parallel genetic crosses between PLK and CEP strains. In these first successful interstrain crosses, these RFLP markers segregated into 11 distinct genetic linkage groups that showed close correlation with physical linkage groups previously defined by molecular karyotype. Separate linkage maps, constructed for each of the 11 chromosomes, indicated recombination frequencies range from approximately 100 to 300 kb per centimorgan. Preliminary linkage assignments were made for the loci regulating sinefungin resistance (snf-1) on chromosome IX and adenine arabinoside (ara-1) on chromosome V by linkage to RFLP markers. Despite random segregation of separate chromosomes, the majority of chromosomes failed to demonstrate internal recombination events and in 3/19 recombinant progeny no intramolecular recombination events were detected. The relatively low rate of intrachromosomal recombination predicts that tight linkage for unknown genes can be established with a relatively small set of markers. This genetic linkage map should prove useful in mapping genes that regulate drug resistance and other biological phenotypes in this important opportunistic pathogen. PMID:1360931

  19. Linkage to chromosome 1p36 for attention-deficit/hyperactivity disorder traits in school and home settings

    NARCIS (Netherlands)

    Zhou, K.; Asherson, P.; Sham, P.; Franke, B.; Anney, R.J.; Buitelaar, J.K.; Ebstein, R.; Gill, M.; Brookes, K.; Buschgens, C.; Campbell, D.; Chen, W.; Christiansen, H.; Fliers, E.; Gabriels, I.; Johansson, L.; Marco, R.; Mulas, F.; Muller, U.; Mulligan, A.; Neale, B.M.; Rijsdijk, F.; Lambregts-Rommelse, N.N.J.; Uebel, H.; Psychogiou, L.; Xu, X.; Banaschewski, T.; Sonuga-Barke, E.; Eisenberg, J.; Manor, I.; Miranda, A.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Sergeant, J.A.; Steinhausen, H.C.; Taylor, E.; Thompson, M.; Faraone, S.V.

    2008-01-01

    BACKGROUND: Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan

  20. Emergency Linkage Mode of Power Enterprise

    OpenAIRE

    Feng Jie; Yu Zhen; Liu Chao

    2016-01-01

    Power emergency disposal needs take full advantage of the power enterprise within the external emergency power and resources. Based on analyzing and summarizing the relevant experience of domestic and foreign emergency linkage, this paper draws the Emergency Linkage subjects, Emergency Linkage contents, Emergency Linkage level, which are three key elements if power enterprise Emergency Linkage. Emergency Linkage subjects are divided into the two types of inner subjects and the external body; ...

  1. A linkage study of bipolar disorder

    Energy Technology Data Exchange (ETDEWEB)

    Kelsoe, J.R. [Univ. of California, San Diego (United States); Sadovnick, A.D.; Remick, R.A. [Univ. of British Columbia, Vancouver (Canada)] [and others

    1994-09-01

    We are currently surveying the genome with polymorphic DNA markers in search of loci linked to bipolar disorder (manic-depressive illness) in three populations: 20 families (175 subjects) from the general North American population from San Diego (UCSD) and Vancouver (UBC); 3 Icelandic families (55 subjects); and an Old Order Amish pedigree 110 (118 subjects). Over 50 markers on chromosomes 1, 2, 5, 11, 17, 18, 20 and 21 have been examined. All markers have been tested in the Amish and Icelandic families, and a portion of them in the UCSD/UBC families, which we have only recently begun genotyping. The following candidate genes have been examined: {beta}-TSH, dopamine transporter (HDAT), {beta}2 adrenergic receptor (ADRB2), glucocorticoid type II receptor (GRL), D2 dopamine receptor, serotonin transporter (HSERT), and G{alpha}s G protein subunit (GNAS1). Linkage analysis was conducted using an autosomal dominant model with age-dependent reduced penetrance. Subjects with bipolar, schizoaffective, or recurrent major depressive disorders were considered affected. No significant evidence for linkage was obtained. Mildly positive lods ranging between 1.1 and 1.6 were obtained for three loci: D11S29, HDAT, and GRL.

  2. North-South Business Linkages

    DEFF Research Database (Denmark)

    Sørensen, Olav Jull; Kuada, John

    2006-01-01

    Based on empirical studies of linkages between TNCs and local firms in India, Malaysia, Vietnam, Ghana and South Africa, five themes are discussed and related to present theoretical perspectives. The themes are (1) Linakge Governance; (2) Globalisation and the dynamics in developing countries (the...... TNC-driven markets in developing countries); (3) The upgrading impact of FDI; (4) Non-equity linkages as a platform for business development, and (5) The learning perspective on international business linakges. The chapter offers at the end a three-dimanional model for impacts of business linkages....

  3. ICAM-2 expression mediates a membrane-actin link, confers a nonmetastatic phenotype and reflects favorable tumor stage or histology in neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Karina Jin Yoon

    Full Text Available The actin cytoskeleton is a primary determinant of tumor cell motility and metastatic potential. Motility and metastasis are thought to be regulated, in large part, by the interaction of membrane proteins with cytoplasmic linker proteins and of these linker proteins, in turn, with actin. However, complete membrane-to-actin linkages have been difficult to identify. We used co-immunoprecipitation and competitive peptide assays to show that intercellular adhesion molecule-2 (ICAM-2/alpha-actinin/actin may comprise such a linkage in neuroblastoma cells. ICAM-2 expression limited the motility of these cells and redistributed actin fibers in vitro, and suppressed development of disseminated tumors in an in vivo model of metastatic neuroblastoma. Consistent with these observations, immunohistochemical analysis demonstrated ICAM-2 expression in primary neuroblastoma tumors exhibiting features that are associated with limited metastatic disease and more favorable clinical outcome. In neuroblastoma cell lines, ICAM-2 expression did not affect AKT activation, tumorigenic potential or chemosensitivity, as has been reported for some types of transfected cells. The observed ICAM-2-mediated suppression of metastatic phenotype is a novel function for this protein, and the interaction of ICAM-2/alpha-actinin/actin represents the first complete membrane-linker protein-actin linkage to impact tumor cell motility in vitro and metastatic potential in an in vivo model. Current work focuses on identifying specific protein domains critical to the regulation of neuroblastoma cell motility and metastasis and on determining if these domains represent exploitable therapeutic targets.

  4. Linkage of morphological markers in brassica

    International Nuclear Information System (INIS)

    Morphological markers play a pivotal role in selection of desirable traits in all plant breeding programs. The genetic linkage maps provide the basic information about the nature and place of genes on genetic maps. Two plant introduction (PI) germplasm of Brassica napus i.e. PI409024 and PI 535850 were inter specifically hybridized to 366 and 1203 lines of B. campestris. The hybrids i.e. 409024 x 1203 and crusher x 1203 were grown to produce F1 generation. The F1 populations were evaluated for genetic nature of four morphological qualitative traits like plant color, flower color, leaf shape and leaf pubescence at the KPK Agricultural University, Peshawar. In F1 generation dark green plant color (C), dark yellow flower color (Y), entire leaf shape (E1) and non-hairiness of leaf (h) were expressed as dominant traits. In F2 generation the hybrids segregated and were classified into their respective phenotypic classes. Linkages were detected between Y and H, and E1 and H, pairs of loci. The recombination frequency between Y and H loci was 17.7+- 10.3 cM, and between E1 and H was 32.3 +- 9.9 cM. (author)

  5. Emergency Linkage Mode of Power Enterprise

    Directory of Open Access Journals (Sweden)

    Feng Jie

    2016-01-01

    Full Text Available Power emergency disposal needs take full advantage of the power enterprise within the external emergency power and resources. Based on analyzing and summarizing the relevant experience of domestic and foreign emergency linkage, this paper draws the Emergency Linkage subjects, Emergency Linkage contents, Emergency Linkage level, which are three key elements if power enterprise Emergency Linkage. Emergency Linkage subjects are divided into the two types of inner subjects and the external body; Emergency Linkage contents are in accordance with four phases of prevention, preparedness, response and recovery; Emergency Linkage level is divided into three levels of enterprise headquarter, provincial enterprise and incident unite. Binding power enterprise emergency management practice, this paper studies the internal Emergency Linkage modes (including horizontal mode and vertical mode, external Emergency Linkage mode and comprehensive Emergency Linkage Mode of power enterprise based on Fishbone Diagram and Process Management Technology.

  6. From Enclave to Linkage Economies?

    DEFF Research Database (Denmark)

    Hansen, Michael W.

    If African developing countries are to benefit fully from the current boom in foreign direct investment (FDI) in extractives (i.e. mining and oil/gas), it is essential that the foreign investors foster linkages to the local economy. Traditionally, extractive FDI in Africa has been seen as the enc......If African developing countries are to benefit fully from the current boom in foreign direct investment (FDI) in extractives (i.e. mining and oil/gas), it is essential that the foreign investors foster linkages to the local economy. Traditionally, extractive FDI in Africa has been seen...... as the enclave economy par excellence, moving in with fully integrated value chains, extracting resources and exporting them as commodities having virtually no linkages to the local economy. However, new opportunities for promoting linkages are offered by changing business strategies of local African enterprises...

  7. From expression pattern to genetic association in asthma and asthma-related phenotypes

    Directory of Open Access Journals (Sweden)

    Vaillancourt Vanessa T

    2012-11-01

    Full Text Available Abstract Background Asthma is a complex disease characterized by hyperresponsiveness, obstruction and inflammation of the airways. To date, several studies using different approaches as candidate genes approach, genome wide association studies, linkage analysis and genomic expression leaded to the identification of over 300 genes involved in asthma pathophysiology. Combining results from two studies of genomic expression, this study aims to perform an association analysis between genes differently expressed in bronchial biopsies of asthmatics compared to controls and asthma-related phenotypes using the same French-Canadian Caucasian population. Results Before correction, 31 of the 85 genes selected were associated with at least one asthma-related phenotype. We found four genes that survived the correction for multiple testing. The rs11630178 in aggrecan gene (AGC1 is associated with atopy (p=0.0003 and atopic asthma (p=0.0001, the rs1247653 in the interferon alpha-inducible protein 6 (IFI6, the rs1119529 in adrenergic, alpha-2A-, receptor (ADRA2A and the rs13103321 in the alcohol dehydrogenase 1B (class I, beta polypeptide (ADH1B, are associated with asthma (p=0.019; 0.01 and 0.002 respectively. Conclusion To our knowledge, this is the first time those genes are associated with asthma and related traits. Consequently, our study confirms that genetic and expression studies are complementary to identify new candidate genes and to investigate their role to improve the comprehension of the complexity of asthma pathophysiology.

  8. Effect of genetic heterogeneity and assortative mating on linkage analysis: a simulation study.

    OpenAIRE

    Falk, C T

    1997-01-01

    Linkage studies of complex genetic traits raise questions about the effects of genetic heterogeneity and assortative mating on linkage analysis. To further understand these problems, I have simulated and analyzed family data for a complex genetic disease in which disease phenotype is determined by two unlinked disease loci. Two models were studied, a two-locus threshold model and a two-locus heterogeneity model. Information was generated for a marker locus linked to one of the disease-definin...

  9. Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps

    OpenAIRE

    Zhang, Weihua; Collins, Andrew; Gibson, Jane; Tapper, William J; Hunt, Sarah; Deloukas, Panos; Bentley, David R.; Morton, Newton E.

    2004-01-01

    Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Popu...

  10. Linkage mapping bovine EST-based SNP

    Directory of Open Access Journals (Sweden)

    Bennett Gary L

    2005-05-01

    Full Text Available Abstract Background Existing linkage maps of the bovine genome primarily contain anonymous microsatellite markers. These maps have proved valuable for mapping quantitative trait loci (QTL to broad regions of the genome, but more closely spaced markers are needed to fine-map QTL, and markers associated with genes and annotated sequence are needed to identify genes and sequence variation that may explain QTL. Results Bovine expressed sequence tag (EST and bacterial artificial chromosome (BACsequence data were used to develop 918 single nucleotide polymorphism (SNP markers to map genes on the bovine linkage map. DNA of sires from the MARC reference population was used to detect SNPs, and progeny and mates of heterozygous sires were genotyped. Chromosome assignments for 861 SNPs were determined by twopoint analysis, and positions for 735 SNPs were established by multipoint analyses. Linkage maps of bovine autosomes with these SNPs represent 4585 markers in 2475 positions spanning 3058 cM . Markers include 3612 microsatellites, 913 SNPs and 60 other markers. Mean separation between marker positions is 1.2 cM. New SNP markers appear in 511 positions, with mean separation of 4.7 cM. Multi-allelic markers, mostly microsatellites, had a mean (maximum of 216 (366 informative meioses, and a mean 3-lod confidence interval of 3.6 cM Bi-allelic markers, including SNP and other marker types, had a mean (maximum of 55 (191 informative meioses, and were placed within a mean 8.5 cM 3-lod confidence interval. Homologous human sequences were identified for 1159 markers, including 582 newly developed and mapped SNP. Conclusion Addition of these EST- and BAC-based SNPs to the bovine linkage map not only increases marker density, but provides connections to gene-rich physical maps, including annotated human sequence. The map provides a resource for fine-mapping quantitative trait loci and identification of positional candidate genes, and can be integrated with other

  11. Diagnosis, assessment, and phenotyping of COPD

    DEFF Research Database (Denmark)

    Lange, Peter; Halpin, David M; O'Donnell, Denis E;

    2016-01-01

    biomarkers to confirm and further assess the diagnosis of COPD. However, it is possible to identify patients who display different phenotypic characteristics of COPD that relate to clinically relevant outcomes. Currently, validated phenotypes of COPD include alpha-1 antitrypsin deficiency, and "frequent...... exacerbators". Recently, a definition and assessment of a new phenotype comprising patients with overlapping features of asthma and COPD has been suggested and is known as "asthma COPD overlap syndrome". Several other phenotypes have been proposed, but require validation against clinical outcomes. Defining...

  12. Buffett's Alpha

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

    Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

  13. Negro alpha-thalassaemia: genetic studies in homozygous sickle cell disease.

    OpenAIRE

    Serjeant, G. R.; Mason, K P; Serjeant, B E

    1980-01-01

    Interaction with the alpha-thalassaemia phenotypes lowers the proportion of Hb S in the sickle cell trait and influences the mean cell volume and proportional Hb A2 in homozygous sickle cell (SS) disease. By assigning somewhat arbitrary values to the alpha-thalassaemia 1 and alpha-thalassaemia 2 phenotypes in these conditions, it has been possible to investigate the patterns of inheritance of alpha-thalassaemia in black populations. The results strongly support the hypothesis that the alpha-t...

  14. Broad scan linkage analysis in a large Tourette family pedigree

    Energy Technology Data Exchange (ETDEWEB)

    Peiffer, A.; Leppert, M. [Univ. of Utah Health Sciences Center, Salt Lake City, UT (United States); Wetering, B.J.M. van der [Univ. Hospital Rotterdam (Netherlands)

    1994-09-01

    Attempts to find a gene causing Tourette syndrome (TS) using linkage analysis have been unsuccessful even though as much as 65% of the autosomal genetic map has been excluded by the pooled results from several laboratories collaborating worldwide. One reason for this failure may be the misclassification of affection status of marry-in spouses. Specifically, we have found that six unrelated spouses in our Utah TS pedigree suffer from TS, obsessive-compulsive disorder or chronic motor tics. In light of these findings we decided to conduct a complete genomic scan from this Utah kindred with polymorphic markers in three related sibships in which there was no assortative mating. A linkage study assuming autosomal dominant inheritance was done using tetranucleotide repeat markers developed at the University of Utah. We selected markers that were less than 300 bp in size and that gave a heterozygosity of over 70% upon analysis in 4 CEPH families. Results to date with 95 markers run at an interval of 30 cM (covering 61% of the genome) show no evidence of linkage. We intend to extend the coverage to 100% of the genome. Pending completion of this scan, failure to provide evidence of linkage in our TS pedigree might then be attributed to phenotypic misclassification or erroneous assumptions regarding the genetic model of transmission.

  15. The dissociation of tumor-induced weight loss from hypoglycemia in a transplantable pluripotent rat islet tumor results in the segregation of stable alpha- and beta-cell tumor phenotypes

    DEFF Research Database (Denmark)

    Madsen, O D; Karlsen, C; Nielsen, E;

    1993-01-01

    that of starved rats until death results from cachexia. After tumor resection, animals immediately resume normal feeding behavior. Comparative studies of hormone release and mRNA content in anorectic lines, MSL-G-AN and NHI-5B-AN, vs. those in the insulinoma line, MSL-G2-IN, revealed selective glucagon gene...... expression in both of the anorectic tumors, whereas insulin and islet amyloid polypeptide gene expression were confined to the insulinoma. Both tumor phenotypes produced cholecystokinin and gastrin in variable small amounts, making it unlikely that these hormones contribute to the anorectic phenotype. Tumor...

  16. The phenotypic features of osteogenesis imperfecta resulting from a mutation of the carboxyl-terminal pro alpha 1(I) propeptide that impairs the assembly of type I procollagen and formation of the extracellular matrix

    NARCIS (Netherlands)

    Cole, WG; Chow, CW; Bateman, JF; Sillence, DO

    1996-01-01

    The features of a baby with lethal perinatal osteogenesis imperfecta (OI-II), resulting from the substitution of tryptophan 94 by cysteine in the carboxyl-terminal propeptide of pro alpha 1(I) chains of type I procollagen, were studied. The limbs and torso were of normal length, shape, and proportio

  17. Alpha fetoprotein

    Science.gov (United States)

    Fetal alpha globulin; AFP ... Greater than normal levels of AFP may be due to: Cancer in testes , ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer ...

  18. Linkage analysis in Marfan syndrome.

    OpenAIRE

    Schwartz, R C; Blanton, S H; Hyde, C A; Sottile, T R; Hudgins, L.; Sarfarazi, M; Tsipouras, P

    1990-01-01

    We have analysed 40 marker loci on 13 chromosomes for linkage with Marfan syndrome. None of the loci was linked to the Marfan syndrome locus at theta = 0.00. This study provides a basis for an exclusion map and for further collaboration in mapping of the locus.

  19. Irish study of high-density Schizophrenia families: Field methods and power to detect linkage

    Energy Technology Data Exchange (ETDEWEB)

    Kendler, K.S.; Straub, R.E.; MacLean, C.J. [Virginia Commonwealth Univ., Richmond, VA (United States)] [and others

    1996-04-09

    Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/or hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one of whom had schizophrenia (S) or poor-outcome schizoaffective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. 75 refs., 6 tabs.

  20. Transformation of maltose into prebiotic isomaltooligosaccharides by a novel alpha-glucosidase from Xantophyllomyces dendrorhous

    OpenAIRE

    Fernández Arrojo, Lucía; Marín Alberdi, Dolores; Gómez de Segura, María Aránzazu; Linde López, Dolores; Alcalde Galeote, Miguel; Gutiérrez Alonso, Patricia; Ghazi, Iraj; Plou Gasca, Francisco José; Fernández Lobato, María; Ballesteros Olmo, Antonio

    2007-01-01

    The transglycosylation activity of a novel alpha-glucosidase from the basidiomycetous yeast Xanthophyllomyces dendrorhous (formerly Phaffia rhodozyma) was studied using maltose as glucosyl donor. The enzyme synthesized oligosaccharides with alpha-(1-2), alpha-(1-4) and alpha-(1-6) bonds. Using 200 g/l maltose, the yield of oligosaccharides was 53.8 g/l, with prebiotic oligosaccharides containing at least one alpha-(1-6) linkage (panose, 6-O-alpha-glucosyl-maltotriose and 6-O-alpha-isomaltosyl...

  1. Record-linkage for pharmacovigilance in Scotland

    OpenAIRE

    Evans, Josie M M; MacDonald, Thomas M

    1999-01-01

    Record-linkage is the linkage of patient-specific information that is stored separately. Recent advances in computerization have meant that record-linkage techniques in medical research are increasingly being used and refined. In particular, they have made a significant contribution to pharmacovigilance, which involves linking drug exposure to outcomes data. In this article, the contribution of record-linkage in Scotland to medical research is described. The two organizations that utilize rec...

  2. Heritability and Familiality of Temperament and Character Dimensions in Korean Families with Schizophrenic Linkage Disequilibrium

    OpenAIRE

    Lee, Byung Dae; Park, Je Min; Lee, Young Min; Moon, Eunsoo; Jeong, Hee Jeong; Chung, Young In; Yi, Young Mi

    2016-01-01

    Objective Categorical syndromes such as schizophrenia may represent complexes of many continuous psychological structural phenotypes along several dimensions of personality development/degeneration. The present study investigated the heritability and familiality of personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD). Methods We recruited 179 probands (with schizophrenia) as well as, whenever possible, their parents and siblings. We used the Temperament and...

  3. Linkage of atopic dermatitis to chromosomes 4q22, 3p24 and 3q21

    DEFF Research Database (Denmark)

    Christensen, Ulla; Møller-Larsen, Steffen; Nyegaard, Mette;

    2009-01-01

    Atopic dermatitis (AD) is a common, itchy skin disease of complex inheritance characterized by dermal and epidermal inflammation. The heritability is considerable and well documented. To date, four genome scans have examined the AD phenotype, showing replicated linkage at 3p26-22, 3q13-21 and 18q11...

  4. Linkage analysis in familial Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wagstaff, J. (Harvard Medical School, Boston, MA (United States)); Shugart, Y.Y. (Columbia Univ., New York (United States)); Lalande, M. (Harvard Medical School, Boston, MA (United States) Howard Hughes Medical Institute, Boston, MA (United States))

    1993-07-01

    Familial Angelman syndrome (AS) can result from mutations in chromosome 15q11q13 that, when transmitted from father to child, result in no phenotypic abnormality but, when transmitted from mother to child, cause AS. These mutations therefore behave neither as dominant nor as recessive mutations but, rather, show an imprinted mode of inheritance. The authors have analyzed two sibling pairs with AS and a larger family with four AS offspring of three sisters with several recently described microsatellite polymorphisms in the AS region. AS siblings inherited the same maternal alleles at the GABRB3 and GABRA5 loci, and the unaffected siblings of AS individuals inherited the other maternal alleles at these loci. In one of the AS sibling pairs, analysis of a recombination event indicates that the mutation responsible for AS is distal to locus D15S63. This result is consistent with a previously described imprinted submicroscopic deletion causing AS, a deletion that includes loci D15S10, D15S113, and GABRB3, all distal to D15S63. The analysis of the larger AS family provides the first clear demonstration of a new mutation in nondeletion AS. Analysis of linkage of AS to GABRB3 in these three families, on the assumption of imprinted inheritance (i.e., penetrance of an AS mutation is 1 if transmitted maternally and is 0 if transmitted paternally), indicates a maximum lod score of 3.52 at 6 = 0. 34 refs., 4 figs., 1 tab.

  5. $\\alpha_s$ review (2016)

    CERN Document Server

    d'Enterria, David

    2016-01-01

    The current world-average of the strong coupling at the Z pole mass, $\\alpha_s(m^2_{Z}) = 0.1181 \\pm 0.0013$, is obtained from a comparison of perturbative QCD calculations computed, at least, at next-to-next-to-leading-order accuracy, to a set of 6 groups of experimental observables: (i) lattice QCD "data", (ii) $\\tau$ hadronic decays, (iii) proton structure functions, (iv) event shapes and jet rates in $e^+e^-$ collisions, (v) Z boson hadronic decays, and (vi) top-quark cross sections in p-p collisions. In addition, at least 8 other $\\alpha_s$ extractions, usually with a lower level of theoretical and/or experimental precision today, have been proposed: pion, $\\Upsilon$, W hadronic decays; soft and hard fragmentation functions; jets cross sections in pp, e-p and $\\gamma$-p collisions; and photon F$_2$ structure function in $\\gamma\\,\\gamma$ collisions. These 14 $\\alpha_s$ determinations are reviewed, and the perspectives of reduction of their present uncertainties are discussed.

  6. Candidate gene linkage analysis indicates genetic heterogeneity in Marfan syndrome

    Directory of Open Access Journals (Sweden)

    L.V.S. Teixeira

    2011-08-01

    Full Text Available Marfan syndrome (MFS is an autosomal dominant disease of the connective tissue that affects the ocular, skeletal and cardiovascular systems, with a wide clinical variability. Although mutations in the FBN1 gene have been recognized as the cause of the disease, more recently other loci have been associated with MFS, indicating the genetic heterogeneity of this disease. We addressed the issue of genetic heterogeneity in MFS by performing linkage analysis of the FBN1 and TGFBR2 genes in 34 families (345 subjects who met the clinical diagnostic criteria for the disease according to Ghent. Using a total of six microsatellite markers, we found that linkage with the FBN1 gene was observed or not excluded in 70.6% (24/34 of the families, and in 1 family the MFS phenotype segregated with the TGFBR2 gene. Moreover, in 4 families linkage with the FBN1 and TGFBR2 genes was excluded, and no mutations were identified in the coding region of TGFBR1, indicating the existence of other genes involved in MFS. Our results suggest that the genetic heterogeneity of MFS may be greater that previously reported.

  7. The $\\alpha-\\alpha$ fishbone potential revisited

    CERN Document Server

    Day, J P; Elhanafy, M; Smith, E; Woodhouse, R; Papp, Z

    2011-01-01

    The fishbone potential of composite particles simulates the Pauli effect by nonlocal terms. We determine the $\\alpha-\\alpha$ fishbone potential by simultaneously fitting to two-$\\alpha$ resonance energies, experimental phase shifts and three-$\\alpha$ binding energies. We found that essentially a simple gaussian can provide a good description of two-$\\alpha$ and three-$\\alpha$ experimental data without invoking three-body potentials.

  8. Linkages between NAMA - LEDS - MRV

    DEFF Research Database (Denmark)

    Agyemang-Bonsu, William; Benioff, Ron; Cox, Sadie;

    Low Emission Development Strategies (LEDS), Nationally Appropriate Mitigation Actions (NAMAs) and Monitoring, Reporting and Verification (MRV) are three of the key conceptual components emerging as part of the global architecture for a new climate agreement by 2015. The three components are...... how the three components are conceptually interlinked. Identifying the linkages can inform the work on each component and strengthen coordination of work in the context of the three big partnerships; the International Partnership on Mitigation and MRV, the LEDS Global Partnership and the NAMA...

  9. Molecular characterization of Blau syndrome: Genetic linkage to chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, G.; Duivaniemi, H.; Christiano, A. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1994-09-01

    The Blau syndrome is an autosomal, dominantly-inherited disease characterized by multi-organ, tissue-specific inflammation. Its clinical phenotype includes granulomatous uveitis, arthritis and skin rash. The syndrome is unique in that it is the sole human model for a variety of multi-system inflammatory diseases that afflict a significant percentage of the population. Karyotypic analysis of the large, three generation kindred whose disease originally characterized the syndrome was unremarkable. Following exclusion of a number of extracellular matrix candidates genes, a genome-wide search was undertaken of the Blau susceptibility locus. Fifty-seven members of the family were genotyped for about 200 highly polymorphic dinucleotide repeat markers. Linkage analysis was performed using the LINKAGE package of programs under a model of dominant inheritance with reduced penetrance. Five liability classes were used to specify penetrances and phenocopy rates for those affected the arthritis, uveitis, skin rash and combinations thererof. In addition, five age-dependent penetrance classes were used for unaffected individuals. The marker D16S298 gave a maximum lod score of 3.6 at {theta} = 0.05 with two-point analysis. Lod scores for flanking markers were consistent. These data provide convincing evidence that the Blau susceptibility locus is situated within the 16p12-q21 interval. Fine mapping of the candidate interval with additional families exhibiting the Blau phenotype, as well as with more polymorphic markers, is underway.

  10. Fine mapping QTL for resistance to VNN disease using a high-density linkage map in Asian seabass.

    Science.gov (United States)

    Liu, Peng; Wang, Le; Wong, Sek-Man; Yue, Gen Hua

    2016-01-01

    Asian seabass has suffered from viral nervous necrosis (VNN) disease. Our previous study has mapped quantitative trait loci (QTL) for resistance to VNN disease. To fine map these QTL and identify causative genes, we identified 6425 single nucleotide polymorphisms (SNPs) from 85 dead and 94 surviving individuals. Combined with 155 microsatellites, we constructed a genetic map consisting of 24 linkage groups (LGs) containing 3000 markers, with an average interval of 1.27 cM. We mapped one significant and three suggestive QTL with phenotypic variation explained (PVE) of 8.3 to 11.0%, two significant and two suggestive QTL with PVE of 7.8 to 10.9%, for resistance in three LGs and survival time in four LGs, respectively. Further analysis one QTL with the largest effect identified protocadherin alpha-C 2-like (Pcdhac2) as the possible candidate gene. Association study in 43 families with 1127 individuals revealed a 6 bp insertion-deletion was significantly associated with disease resistance. qRT-PCR showed the expression of Pcdhac2 was significantly induced in the brain, muscle and skin after nervous necrosis virus (NNV) infection. Our results could facilitate marker-assisted selection (MAS) for resistance to NNV in Asian seabass and set up the basis for functional analysis of the potential causative gene for resistance.

  11. Alpha One Foundation

    Science.gov (United States)

    ... Tested Find Support Find Doctor What Is Alpha-1? Alpha-1 Antitrypsin Deficiency (Alpha-1) is a ... results for inhaled augmentation More News Our Number One Goal: Find a cure for Alpha-1. Website ...

  12. A RAD-based linkage map and comparative genomics in the gudgeons (genus Gnathopogon, Cyprinidae

    Directory of Open Access Journals (Sweden)

    Kakioka Ryo

    2013-01-01

    Full Text Available Abstract Background The construction of linkage maps is a first step in exploring the genetic basis for adaptive phenotypic divergence in closely related species by quantitative trait locus (QTL analysis. Linkage maps are also useful for comparative genomics in non-model organisms. Advances in genomics technologies make it more feasible than ever to study the genetics of adaptation in natural populations. Restriction-site associated DNA (RAD sequencing in next-generation sequencers facilitates the development of many genetic markers and genotyping. We aimed to construct a linkage map of the gudgeons of the genus Gnathopogon (Cyprinidae for comparative genomics with the zebrafish Danio rerio (a member of the same family as gudgeons and for the future QTL analysis of the genetic architecture underlying adaptive phenotypic evolution of Gnathopogon. Results We constructed the first genetic linkage map of Gnathopogon using a 198 F2 interspecific cross between two closely related species in Japan: river-dwelling Gnathopogon elongatus and lake-dwelling Gnathopogon caerulescens. Based on 1,622 RAD-tag markers, a linkage map spanning 1,390.9 cM with 25 linkage groups and an average marker interval of 0.87 cM was constructed. We also identified a region involving female-specific transmission ratio distortion (TRD. Synteny and collinearity were extensively conserved between Gnathopogon and zebrafish. Conclusions The dense SNP-based linkage map presented here provides a basis for future QTL analysis. It will also be useful for transferring genomic information from a “traditional” model fish species, zebrafish, to screen candidate genes underlying ecologically important traits of the gudgeons.

  13. Synthesis of deoxycytidine oligomers containing phosphorodithioate linkages

    DEFF Research Database (Denmark)

    Grandas, Ana; Marshall, William S.; Nielsen, John;

    1989-01-01

    Deoxydicytidine phosphoramidite, 4-chlorobenzylmercaptan and tetrazole reacted to form dinucleoside thiophosphite. Oxidation with sulfur yields phosphorodithioates which were used to synthesize pentadecadeoxyoligonucleotides containing nuclease resistant phosphorodithioate internucleotide linkages...

  14. Joint Modeling of Linkage and Association: Identifying SNPs Responsible for a Linkage Signal

    OpenAIRE

    Li, Mingyao; Boehnke, Michael; Abecasis, Gonçalo R

    2005-01-01

    Once genetic linkage has been identified for a complex disease, the next step is often association analysis, in which single-nucleotide polymorphisms (SNPs) within the linkage region are genotyped and tested for association with the disease. If a SNP shows evidence of association, it is useful to know whether the linkage result can be explained, in part or in full, by the candidate SNP. We propose a novel approach that quantifies the degree of linkage disequilibrium (LD) between the candidate...

  15. Automated generation of linkage loop equations for planar 1-DOF linkages, demonstrated up to 8-bar

    OpenAIRE

    Parrish, BE; McCarthy, JM; Eppstein, D

    2014-01-01

    Copyright © 2014 by ASME. In this paper we present an algorithm that automatically creates the linkage loop equations for planar 1-DoF linkages of any topology with rotating joints, demonstrated up to 8-bars. The algorithm derives the linkage loop equations from the linkage graph by establishing a cycle basis through a single common edge. Divergent and convergent loops are identified and used to establish the fixed angles of the ternary and higher links. Results demonstrate the automated gene...

  16. Folate receptor {alpha} regulates cell proliferation in mouse gonadotroph {alpha}T3-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Congjun; Evans, Chheng-Orn [Department of Neurosurgery and Laboratory of Molecular Neurosurgery and Biotechnology, Emory University, School of Medicine, Atlanta, Georgia (United States); Stevens, Victoria L. [Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia (United States); Owens, Timothy R. [Emory University, School of Medicine, Atlanta, Georgia (United States); Oyesiku, Nelson M., E-mail: noyesik@emory.edu [Department of Neurosurgery and Laboratory of Molecular Neurosurgery and Biotechnology, Emory University, School of Medicine, Atlanta, Georgia (United States)

    2009-11-01

    We have previously found that the mRNA and protein levels of the folate receptor alpha (FR{alpha}) are uniquely over-expressed in clinically human nonfunctional (NF) pituitary adenomas, but the mechanistic role of FR{alpha} has not fully been determined. We investigated the effect of FR{alpha} over-expression in the mouse gonadotroph {alpha}T3-1 cell line as a model for NF pituitary adenomas. We found that the expression and function of FR{alpha} were strongly up-regulated, by Western blotting and folic acid binding assay. Furthermore, we found a higher cell growth rate, an enhanced percentage of cells in S-phase by BrdU assay, and a higher PCNA staining. These observations indicate that over-expression of FR{alpha} promotes cell proliferation. These effects were abrogated in the same {alpha}T3-1 cells when transfected with a mutant FR{alpha} cDNA that confers a dominant-negative phenotype by inhibiting folic acid binding. Finally, by real-time quantitative PCR, we found that mRNA expression of NOTCH3 was up-regulated in FR{alpha} over-expressing cells. In summary, our data suggests that FR{alpha} regulates pituitary tumor cell proliferation and mechanistically may involve the NOTCH pathway. Potentially, this finding could be exploited to develop new, innovative molecular targeted treatment for human NF pituitary adenomas.

  17. Linkage Disequilibrium Mapping of Meat Quality QTL

    Science.gov (United States)

    Previous studies based on linkage analysis have identified broad areas in the bovine genome associated with meat quality. Linkage disequilibrium (LD) analyses have the potential to identify narrower regions and point towards candidate genes. Tenderness and marbling were chosen to be evaluated in a ...

  18. Association and linkage analysis of COL1A1 and AHSG gene polymorphisms with femoral neck bone geometric parameters in both Caucasian and Chinese nuclear families

    Institute of Scientific and Technical Information of China (English)

    Hui JIANG; Shu-feng LEI; Su-mei XIAO; Yuan CHEN; Xiao SUN; Fang YANG; Li-ming LI; Shun WU; Hong-wen DENC

    2007-01-01

    Aim: To simultaneously investigate the contribution of the alpha 1 chain of col-lagen type 1 (COL1A1) and alpha2-HS-glycoprotein (AHSG) genes to the varia-tion of bone geometric parameters in both Caucasians and Chinese. Methods: Six hundred and five Caucasian individuals from 157 nuclear families and 1228 Chi-nese subjects from 400 nuclear families were genotyped at the AHSG-Sacl, COL1A1-PCOL2 and Sp1 polymorphisms using polymerase chain reaction (PCR)-restric-tion fragment length polymorphism (RFLP). 5 FN bone geometric parameters were calculated based on bone mineral density and bone area of femoral neck (FN)measured by dual energy X-ray absorptiometry. Population stratification, total family association, within-family association, and linkage tests were performed by the quantitative transmission disequilibrium test program. Results: The t-test showed the significant differences of all bone geometric phenotypes (except ED)between Caucasians and Chinese in the offspring using both unadjusted and adjusted (by age, height, weight, and gender) data. In Caucasians, we found significant within-family association results between the COL1A1-Sp1 polymor-phism (rs1800012) and cross sectional area (CSA), cortical thickness (CT),endocortical diameter (ED), buckling ratio (BR) (P=0.018, 0.002, 0.023, and 0.001,respectively); the COL1A1-Sp1 polymorphism also detected significant linkage with BR (P=0.039). In the population of China, the within-family associations between the COL1A1-PCOL2 polymorphism (rs1107946) and CT, BR were signifi-cant (P=0.012 and 0.008, respectively). Furthermore, evidence of linkage were observed between the AHSG-SacI polymorphism (rs4918) and CT, BR (P--0.042 and 0.014, respectively) in Caucasians, but not in Chinese. Conclusion: Our results suggest that the COL1A1 gene may have significantly association with bone geometry in both Caucasians and Chinese, and the AHSG gene may be linked to bone geometry in Caucasians, but not in Chinese. This study

  19. An approach to investigating linkage for bipolar disorder using large Costa Rican pedigrees

    Energy Technology Data Exchange (ETDEWEB)

    Freimer, N.B.; Reus, V.I.; Vinogradov, S. [Univ. of California, San Francisco, CA (United States)] [and others

    1996-05-31

    Despite the evidence that major gene effects exist for bipolar disorder (BP), efforts to map BP loci have so far been unsuccessful. A strategy for mapping BP loci is described, focused on investigation of large pedigrees from a genetically homogenous population, that of Costa Rica. This approach is based on the use of a conservative definition of the BP phenotype in preparation for whole genome screening with polymorphic markers. Linkage simulation analyses are utilized to indicate the probability of detecting evidence suggestive of linkage, using these pedigrees. These analyses are performed under a series of single locus models, ranging form recessive to nearly dominant, utilizing both lod score and affected pedigree member analyses. Additional calculations demonstrate that with any of the models employed, most of the information for linkage derives from affected rather than unaffected individuals. 26 refs., 2 figs., 5 tabs.

  20. Resource linkages and sustainable development

    Science.gov (United States)

    Anouti, Yahya

    Historically, fossil fuel consumers in most developing hydrocarbon-rich countries have enjoyed retail prices at a discount from international benchmarks. Governments of these countries consider the subsidy transfer to be a means for sharing the wealth from their resource endowment. These subsidies create negative economic, environmental, and social distortions, which can only increase over time with a fast growing, young, and rich population. The pressure to phase out these subsidies has been mounting over the last years. At the same time, policy makers in resource-rich developing countries are keen to obtain the greatest benefits for their economies from the extraction of their exhaustible resources. To this end, they are deploying local content policies with the aim of increasing the economic linkages from extracting their resources. Against this background, this dissertation's three essays evaluate (1) the global impact of rationalizing transport fuel prices, (2) how resource-rich countries can achieve the objectives behind fuel subsidies more efficiently through direct cash transfers, and (3) the economic tradeoffs from deploying local content policies and the presence of an optimal path. We begin by reviewing the literature and building the case for rationalizing transport fuel prices to reflect their direct costs (production), indirect costs (road maintenance) and negative externalities (climate change, local pollutants, traffic accidents and congestion). To do so, we increase the scope of the economic literature by presenting an algorithm to evaluate the rationalized prices in different countries. Then, we apply this algorithm to quantify the rationalized prices across 123 countries in a partial equilibrium setting. Finally, we present the first comprehensive measure of the impact of rationalizing fuel prices on the global demand for gasoline and diesel, environmental emissions, government revenues, and consumers' welfare. By rationalizing transport fuel

  1. Spin Transfer in Polymer Degradation of Abnormal Linkage

    Science.gov (United States)

    Yu, Tianrong; Tian, Chuanjin; Liu, Xizhe; Wang, Jia; Gao, Yang; Wang, Zhigang

    2016-09-01

    The degradation of polymer materials plays an important role in production and life. In this work, the degradation mechanism of poly-α-methylstyrene (PAMS) tetramers with abnormal linkage was investigated by using density functional theory (DFT). Calculated results indicate that the head-to-head and the tail-to-tail reactions needed to overcome the energy barriers are about 0.15 eV and about 1.26 eV, respectively. The broken C-C bond at the unsaturated end of the chain leads to the dissociation of alpha-methylstyrene (AMS) monomers one by one. Furthermore, the analyses of bond characteristics are in good agreement with the results of energy barriers. In addition, the spin population analysis presents an interesting net spin transfer process in depolymerization reactions. We hope that the current theoretical results provide useful help to understand the degradation mechanism of polymers.

  2. The CEPH consortium linkage map of human chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Bowcock, A.M.; Barnes, R.I. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Gerken, S.C.; Leppert, M. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States); Shiang, R. [Univ. of Iowa, Iowa City, IA (United States); Jabs, E.W.; Warren, A.C.; Antonarakis, S. [Johns Hopkins School of Medicine, Baltimore, MD (United States); Retief, A.E. [Univ. of Stellenbosch, Tygerberg (South Africa); Vergnaud, G. [Centre d`Etudes du Bouchet, Vert le Petit (France)] [and others

    1993-05-01

    The CEPH consortium map of chromosome 13 is presented. This map contains 59 loci defined by genotypes generated from CEPH family DNAs with 94 different probe and restriction enzyme combinations contributed by 9 laboratories. A total of 25 loci have been placed on the map with likelihood support of at least 1000:1. The map extends from loci in the centromeric region of chromosome 13 to the terminal band of the long arm. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 158, 203, and 178cM respectively. The largest interval is 24 cM and is between D13Z1 (alphaRI) and ATP1AL1. The mean genetic distance between the 25 uniquely placed loci is 7 cM. 76 refs., 3 figs., 5 tabs.

  3. Structures and apoprotein linkages of phycoerythrobilin and phycocyanobilin.

    Science.gov (United States)

    Killilea, S D; O'Carra, P; Murphy, R F

    1980-05-01

    Phycoerythrobilin and phycocyanobilin are covalently attached to the apoproteins of phycoerythrins and phycocyanins. One linkage consists of an ester bond between the hydroxy group of a serine residue and the propionate side chain on one of the inner pyrrole rings (probably ring C). The other linkage is a labile thioether bond between a cysteine residue and the two-carbon side chain on pyrrole ring A. This side chain and both of the alpha-positions of the ring A are in the reduced state. This constitutes an important structural revision, since, in the structures currently accepted for the phycobilins, the two-carbon side chain on ring A is depicted as an ethylidene grouping and this has been regarded not only as a very characteristic feature of the phycobilins, but also as a probable structural feature of the chromophore of phytochrome, largely on the basis of other analogies with the phycobilins. The ethylidene-containing structures apply instead to artefact forms of the pigments released from the apoproteins by treatment with hot methanol. Cleavage of the ring-A linkage involves an elimination reaction releasing the cysteine residue and generating a double bond in the ring-A side chain. During cleavage in methanol the direction of the elimination is towards the ring, generating the ethylidene double bond. Since this is linked to the conjugated system, the methanol-released pigments differ spectrally from the native phycobilins. During acid-catalysed release of the pigments, the elimination apparently goes in the opposite direction, generating a double bond at the outer position of the side chain. Since this double bond is not linked to the conjugated system, the acid-released pigments remain spectrally identical with their protein-bound counterparts. PMID:7396852

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

    Science.gov (United States)

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

    2014-02-15

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

  5. Multipoint linkage-disequilibrium mapping narrows location interval and identifies mutation heterogeneity

    OpenAIRE

    Morris, Andrew P.; Whittaker, John C; Xu, Chun-Fang; Hosking, Louise K.; Balding, David J.

    2003-01-01

    Single-nucleotide polymorphism (SNP) genotypes were recently examined in an 890-kb region flanking the human gene CYP2D6. Single-marker and haplotype-based analyses identified, with genomewide significance (P < 10-7), a 403-kb interval displaying strong linkage disequilibrium (LD) with predicted poor-metabolizer phenotype. However, the width of this interval makes the location of causal variants difficult: for example, the interval contains seven known or predicted genes in addition to CYP2D6...

  6. An integrative method for testing form–function linkages and reconstructed evolutionary pathways of masticatory specialization

    OpenAIRE

    Tseng, Z. Jack; Flynn, John J.

    2015-01-01

    Morphology serves as a ubiquitous proxy in macroevolutionary studies to identify potential adaptive processes and patterns. Inferences of functional significance of phenotypes or their evolution are overwhelmingly based on data from living taxa. Yet, correspondence between form and function has been tested in only a few model species, and those linkages are highly complex. The lack of explicit methodologies to integrate form and function analyses within a deep-time and phylogenetic context we...

  7. DYNAMIC DESIGN OF VARIABLE SPEED PLANAR LINKAGES

    Institute of Scientific and Technical Information of China (English)

    Yao Yanan; Yan Hongsen; Zou Huijun

    2005-01-01

    A method for improving dynamic characteristics of planar linkages by actively varying the speed function of the input link is presented. Design criteria and constraints for the dynamic design of variable speed planar linkages are developed. Both analytical and optimization approaches for determining suitable input speed functions to minimize the driving torque, the shaking moment, or both simultaneously of planar linkages, subject to various design requirements and constraints, are derived.Finally, some examples are given to illustrate the design procedure and to verify its feasibility.

  8. A COMPARISON BETWEEN SINGLE LINKAGE AND COMPLETE LINKAGE IN AGGLOMERATIVE HIERARCHICAL CLUSTER ANALYSIS FOR IDENTIFYING TOURISTS SEGMENTS

    OpenAIRE

    Noor Rashidah Rashid

    2012-01-01

    Cluster Analysis is a multivariate method in statistics. Agglomerative Hierarchical Cluster Analysis is one of approaches in Cluster Analysis. There are two linkage methods in Agglomerative Hierarchical Cluster Analysis which are Single Linkage and Complete Linkage. The purpose of this study is to compare between Single Linkage and Complete Linkage in Agglomerative Hierarchical Cluster Analysis. The comparison of performances between these linkage methods was shown by using Kruskal-Wallis tes...

  9. A first generation microsatellite- and SNP-based linkage map of Jatropha.

    Directory of Open Access Journals (Sweden)

    Chun Ming Wang

    Full Text Available Jatropha curcas is a potential plant species for biodiesel production. However, its seed yield is too low for profitable production of biodiesel. To improve the productivity, genetic improvement through breeding is essential. A linkage map is an important component in molecular breeding. We established a first-generation linkage map using a mapping panel containing two backcross populations with 93 progeny. We mapped 506 markers (216 microsatellites and 290 SNPs from ESTs onto 11 linkage groups. The total length of the map was 1440.9 cM with an average marker space of 2.8 cM. Blasting of 222 Jatropha ESTs containing polymorphic SSR or SNP markers against EST-databases revealed that 91.0%, 86.5% and 79.2% of Jatropha ESTs were homologous to counterparts in castor bean, poplar and Arabidopsis respectively. Mapping 192 orthologous markers to the assembled whole genome sequence of Arabidopsis thaliana identified 38 syntenic blocks and revealed that small linkage blocks were well conserved, but often shuffled. The first generation linkage map and the data of comparative mapping could lay a solid foundation for QTL mapping of agronomic traits, marker-assisted breeding and cloning genes responsible for phenotypic variation.

  10. Simple Sequence Repeat Genetic Linkage Maps of A-genome Diploid Cotton (Gossypium arboreum)

    Institute of Scientific and Technical Information of China (English)

    Xue-Xia Ma; Bao-Liang Zhou; Yan-Hui Lü; Wang-Zhen Guo; Tian-Zhen Zhang

    2008-01-01

    This study introduces the construction of the first intraspacific genetic linkage map of the A-genome diploid cotton with newly developed simple sequence repeat (SSR) markers using 189 F2 plants derived from the cross of two Asiatic parents were detected using 6 092 pairs of SSR primers. Two-hundred and sixty-eight pairs of SSR pdmers with better polymorphisms were picked out to analyze the F2 population. In total, 320 polymorphic bands were generated and used to construct a linkage map with JoinMap3.0. Two-hundred and sixty-seven loci, Including three phenotypic traits were mapped at a logarithms of odds ratio (LOD) ≥ 3.0 on 13 linkage groups. The total length of the map was 2 508.71 cM, and the average distance between adjacent markers was 9.40 cM. Chromosome assignments were according to the association of linkages with our backbone tetraploid specific map using the 89 similar SSR loci. Comparisons among the 13 suites of orthologous linkage groups revealed that the A-genome chromosomes are largely collinear with the At and Dt sub-genome chromosomes. Chromosomes associated with inversions suggested that allopolyploidization was accompanied by homologous chromosomal rearrangement. The inter-chromosomal duplicated loci supply molecular evidence that the A-genome diploid Asiatic cotton is paleopolyploid.

  11. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    2011-01-01

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  12. Cumulant dynamics in a finite population linkage equilibrium theory

    CERN Document Server

    Rattray, M; Rattray, Magnus; Shapiro, Jonathan L.

    1999-01-01

    The evolution of a finite population at linkage equilibrium is described in terms of the dynamics of phenotype distribution cumulants. This provides a powerful method for describing evolutionary transients and we elucidate the relationship between the cumulant dynamics and the diffusion approximation. A separation of time-scales between the first and higher cumulants for low mutation rates is demonstrated in the diffusion limit and provides a significant simplification of the dynamical system. However, the diffusion limit may not be appropriate for strong selection as the standard Fisher-Wright model of genetic drift can break down in this case. Two novel examples of this effect are considered: we shown that the dynamics may depend on the number of loci under strong directional selection and that environmental variance results in a reduced effective population size. We also consider a simple model of a changing environment which cannot be described by a diffusion equation and we derive the optimal mutation ra...

  13. Analysis of malaria parasite phenotypes using experimental genetic crosses of Plasmodium falciparum

    OpenAIRE

    Ranford-Cartwright, Lisa C; Mwangi, Jonathan M.

    2012-01-01

    We review the principles of linkage analysis of experimental genetic crosses and their application to Plasmodium falciparum. Three experimental genetic crosses have been performed using the human malaria parasite P. falciparum. Linkage analysis of the progeny of these crosses has been used to identify parasite genes important in phenotypes such as drug resistance, parasite growth and virulence, and transmission to mosquitoes. The construction and analysis of genetic maps has been used to char...

  14. Linkage disequilibrium in wild mice.

    Directory of Open Access Journals (Sweden)

    Cathy C Laurie

    2007-08-01

    Full Text Available Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1 Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2 they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3 LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits.

  15. An estimating function approach to linkage heterogeneity

    Indian Academy of Sciences (India)

    He Gao; Ying Zhou; Weijun Ma; Haidong Liu; Linan Zhao

    2013-12-01

    Testing linkage heterogeneity between two loci is an important issue in genetics. Currently, there are four methods (K-test, A-test, B-test and D-test) for testing linkage heterogeneity in linkage analysis, which are based on the likelihood-ratio test. Among them, the commonly used methods are the K-test and A-test. In this paper, we present a novel test method which is different from the above four tests, called G-test. The new test statistic is based on estimating function, possessing a theoretic asymptotic distribution, and therefore demonstrates its own advantages. The proposed test is applied to analyse a real pedigree dataset. Our simulation results also indicate that the G-test performs well in terms of power of testing linkage heterogeneity and outperforms the current methods to some degree.

  16. Connectivity and Linkages Between Isolated Habitat

    Data.gov (United States)

    California Department of Resources — Proposed areas where connectiviy and linkages between isolated habitat on the San Joaquin Valley floor and natural lands in the surrounding foothills should be...

  17. Resource linkages and sustainable development

    Science.gov (United States)

    Anouti, Yahya

    Historically, fossil fuel consumers in most developing hydrocarbon-rich countries have enjoyed retail prices at a discount from international benchmarks. Governments of these countries consider the subsidy transfer to be a means for sharing the wealth from their resource endowment. These subsidies create negative economic, environmental, and social distortions, which can only increase over time with a fast growing, young, and rich population. The pressure to phase out these subsidies has been mounting over the last years. At the same time, policy makers in resource-rich developing countries are keen to obtain the greatest benefits for their economies from the extraction of their exhaustible resources. To this end, they are deploying local content policies with the aim of increasing the economic linkages from extracting their resources. Against this background, this dissertation's three essays evaluate (1) the global impact of rationalizing transport fuel prices, (2) how resource-rich countries can achieve the objectives behind fuel subsidies more efficiently through direct cash transfers, and (3) the economic tradeoffs from deploying local content policies and the presence of an optimal path. We begin by reviewing the literature and building the case for rationalizing transport fuel prices to reflect their direct costs (production), indirect costs (road maintenance) and negative externalities (climate change, local pollutants, traffic accidents and congestion). To do so, we increase the scope of the economic literature by presenting an algorithm to evaluate the rationalized prices in different countries. Then, we apply this algorithm to quantify the rationalized prices across 123 countries in a partial equilibrium setting. Finally, we present the first comprehensive measure of the impact of rationalizing fuel prices on the global demand for gasoline and diesel, environmental emissions, government revenues, and consumers' welfare. By rationalizing transport fuel

  18. Identifying nanotechnological linkages in the Finnish economy

    OpenAIRE

    Nikulainen, Tuomo

    2007-01-01

    Nanotechnology, as an emerging science-based technology, is seen to have great potential both in scientific as well as economic terms. In this paper the focus is on identifying the technological linkages between the Finnish nanotechnology community and the industrial incumbents. These technological link-ages are first observed at a broader level in comparison with the technological strengths of the Finnish industries, and then in greater detail at the level of companies. In addition, the abso...

  19. Linkage of health and aged care service events: comparing linkage and event selection methods

    OpenAIRE

    Rosman Diana; Karmel Rosemary

    2008-01-01

    Abstract Background Data linkage is a technique that has long been used to connect information across several disparate data sources – most commonly for medical and population health research. Often the purpose is to connect data for individuals over extended time periods or across different service settings, and so person-based linkage using detailed personal information is preferred. Linkage which aims to link connected events, on the other hand, requires information about the time and plac...

  20. Whole genome linkage disequilibrium maps in cattle

    Directory of Open Access Journals (Sweden)

    Mannen Hideyuki

    2007-10-01

    Full Text Available Abstract Background Bovine whole genome linkage disequilibrium maps were constructed for eight breeds of cattle. These data provide fundamental information concerning bovine genome organization which will allow the design of studies to associate genetic variation with economically important traits and also provides background information concerning the extent of long range linkage disequilibrium in cattle. Results Linkage disequilibrium was assessed using r2 among all pairs of syntenic markers within eight breeds of cattle from the Bos taurus and Bos indicus subspecies. Bos taurus breeds included Angus, Charolais, Dutch Black and White Dairy, Holstein, Japanese Black and Limousin while Bos indicus breeds included Brahman and Nelore. Approximately 2670 markers spanning the entire bovine autosomal genome were used to estimate pairwise r2 values. We found that the extent of linkage disequilibrium is no more than 0.5 Mb in these eight breeds of cattle. Conclusion Linkage disequilibrium in cattle has previously been reported to extend several tens of centimorgans. Our results, based on a much larger sample of marker loci and across eight breeds of cattle indicate that in cattle linkage disequilibrium persists over much more limited distances. Our findings suggest that 30,000–50,000 loci will be needed to conduct whole genome association studies in cattle.

  1. A Novel Non-Parametric Regression Reveals Linkage on Chromosome 4 for the Number of Externalizing Symptoms in Sib-Pairs

    OpenAIRE

    Ghosh, Saurabh; Laura J Bierut; Porjesz, Bernice; Edenberg, Howard J.; Dick, Danielle; Goate, Alison; Hesselbrock, Victor; Nurnberger, John; Foroud, Tatiana; Kramer, John; Rice, John,; Begleiter, Henri

    2008-01-01

    In this report, we present results of a genome-wide linkage scan using as a phenotype the number of externalizing symptoms associated with alcohol use disorders. Subjects were collected by the Collaborative Study on the Genetics of Alcoholism project from families in which at least three first degree relatives were affected by alcohol dependence. We use a novel non-parametric regression method based on kernel smoothing for our analysis. We report a statistically significant linkage close to t...

  2. Hierarchical genetic clusters for phenotypic analysis

    Directory of Open Access Journals (Sweden)

    Luiza Barbosa da Matta

    2015-10-01

    Full Text Available Methods to obtain phenotypic information were evaluated to help breeders choosing the best methodology for analysis of genetic diversity in backcross populations. Phenotypes were simulated for 13 characteristics generated in 10 populations with 100 individuals each. Genotypic information was generated from 100 loci of which 20 were taken at random to determine the characteristics expressing two alleles. Dissimilarity measures were calculated, and genetic diversity was analyzed through hierarchical clustering and graphic projection of the distances. A backcross was performed from the two most divergent populations. A set of characteristics with variable heritability was taken into account. The environmental effect was simulated assuming . For hierarchical clusters, the following methods were used: Gower Method, average linkage within the cluster, average linkage among clusters, the furthest neighbor method, the nearest neighbor method, Ward’s method, and the median method. The environmental effect and heritability of the analyzed variables had an influence on the pattern of hierarchical clustering populations according to the backcrossed generations. The nearest neighbor method was the most efficient in reconstructing the system of backcrossing, and it presented the highest cophenetic correlation. The efficiency of the nearest neighbor method was the highest when the analysis involved characteristics of high heritability.

  3. Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population

    DEFF Research Database (Denmark)

    Hansen, S K; Rose, C S; Glümer, C;

    2005-01-01

    The hepatocyte nuclear factor (HNF)-4alpha is an orphan nuclear receptor, which plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion. The gene encoding HNF-4alpha (HNF4A) is located on chromosome 20q12-q13 in a region that in several studies has shown linkage with type 2...

  4. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    DEFF Research Database (Denmark)

    Bruun, Camilla S.; Jørgensen, Claus B.; Bay, Lene;

    2008-01-01

    of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 and ITGAV orthologs map to SSC15. In an experimentall family (n=113), showing segregation of the trait, the candidate region was confirmed by linkage...... analysis with four microsatellite markers. Mapping of the porcine ITGB6 and ITGAV in the IMpRH radiation hybrid panel confirmed the comparative mapping information. Sequencing of the ITGB6 and ITGAV coding sequences from affected and normal pigs revealed no evidence of a causative mutation, but alternative...... resembling the integrin ß6-/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular and functional analyses have excluded that the mutated phenotype is caused by structural mutations in or ablation of any...

  5. Ab initio alpha-alpha scattering

    CERN Document Server

    Elhatisari, Serdar; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-01-01

    Processes involving alpha particles and alpha-like nuclei comprise a major part of stellar nucleosynthesis and hypothesized mechanisms for thermonuclear supernovae. In an effort towards understanding alpha processes from first principles, we describe in this letter the first ab initio calculation of alpha-alpha scattering. We use lattice effective field theory to describe the low-energy interactions of nucleons and apply a technique called the adiabatic projection method to reduce the eight-body system to an effective two-cluster system. We find good agreement between lattice results and experimental phase shifts for S-wave and D-wave scattering. The computational scaling with particle number suggests that alpha processes involving heavier nuclei are also within reach in the near future.

  6. Ab initio alpha-alpha scattering

    Science.gov (United States)

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A.; Luu, Thomas; Meißner, Ulf-G.

    2015-12-01

    Processes such as the scattering of alpha particles (4He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei—nuclei with even and equal numbers of protons and neutrons—is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the ‘adiabatic projection method’ to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  7. Ab initio alpha-alpha scattering.

    Science.gov (United States)

    Elhatisari, Serdar; Lee, Dean; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-12-01

    Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei--nuclei with even and equal numbers of protons and neutrons--is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the 'adiabatic projection method' to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  8. Inter-organizational linkages and resource dependence

    Directory of Open Access Journals (Sweden)

    Rod B. McNaughton

    2014-12-01

    Full Text Available Few studies have examined the relationship between inter-industry, inter-corporate ownership (ICO patterns and inter-industry resource exchange patterns. Using data from Statistics Canada, this paper reveals a positive association between the degree of ICO linkages and the degree of input–output dependence among Canadian industry groups. This provides empirical support for the primary assertion of resource dependence theory: that corporations employ ICO linkages to manage their input–output dependence resulting from recurrent resource exchanges. This research differs from extant tests of resource dependence in that it uses data for the population of firms (over a size threshold in Canada and includes all forms of interdependence between enterprises. The findings suggest scenarios in which corporations can adopt ICO linkages to manage resource dependence and reduce transaction costs.

  9. Intragroup emotions: physiological linkage and social presence

    Directory of Open Access Journals (Sweden)

    Simo eJärvelä

    2016-02-01

    Full Text Available We investigated how technologically mediating two different components of emotion – communicative expression and physiological state – to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression and visualization of group level physiological heart rates and their dyadic linkage (physiology was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member’s physiological components of emotion by technological means to enhance mediated communication and strengthen social presence.

  10. Some methods for blindfolded record linkage

    Directory of Open Access Journals (Sweden)

    Christen Peter

    2004-06-01

    Full Text Available Abstract Background The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. Methods A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. Results The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. Conclusion Although the protocols described in

  11. The Barley Chromosome 5 Linkage Map

    DEFF Research Database (Denmark)

    Jensen, J.; Jørgensen, Jørgen Helms

    1975-01-01

    The distances between nine loci on barley chromosome 5 have been studied in five two-point tests, three three-point tests, and one four-point test. Our previous chromosome 5 linkage map, which contained eleven loci mapped from literature data (Jensen and Jørgensen 1975), is extended with four loci......-position is fixed on the map by a locus (necl), which has a good marker gene located centrally in the linkage group. The positions of the other loci are their distances in centimorgans from the 0-position; loci in the direction of the short chromosome arm are assigned positive values and those...

  12. Binding Interactions Between alpha-glucans from Lactobacillus reuteri and Milk Proteins Characterised by Surface Plasmon Resonance

    OpenAIRE

    Diemer, Silja K.; Svensson, Birte; Babol, Linnea N.; Cockburn, Darrell; Grijpstra, Pieter; Dijkhuizen, Lubbert; Folkenberg, Ditte M.; Garrigues, Christel; Ipsen, Richard H.

    2012-01-01

    Interactions between milk proteins and alpha-glucans at pH 4.0-5.5 were investigated by use of surface plasmon resonance. The alpha-glucans were synthesised with glucansucrase enzymes from Lactobacillus reuteri strains ATCC-55730, 180, ML1 and 121. Variations in the molecular characteristics of the alpha-glucans, such as molecular weight, linkage type and degree of branching, influenced the interactions with native and denatured beta-lactoglobulin and kappa-casein. The highest overall binding...

  13. Phenotype definition in epilepsy.

    Science.gov (United States)

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  14. Faddeev calculation of 3 alpha and alpha alpha Lambda systems using alpha alpha resonating-group method kernel

    CERN Document Server

    Fujiwara, Y; Kohno, M; Suzuki, Y; Baye, D; Sparenberg, J M

    2004-01-01

    We carry out Faddeev calculations of three-alpha (3 alpha) and two-alpha plus Lambda (alpha alpha Lambda) systems, using two-cluster resonating-group method kernels. The input includes an effective two-nucleon force for the alpha alpha resonating-group method and a new effective Lambda N force for the Lambda alpha interaction. The latter force is a simple two-range Gaussian potential for each spin-singlet and triplet state, generated from the phase-shift behavior of the quark-model hyperon-nucleon interaction, fss2, by using an inversion method based on supersymmetric quantum mechanics. Owing to the exact treatment of the Pauli-forbidden states between the clusters, the present three-cluster Faddeev formalism can describe the mutually related, alpha alpha, 3 alpha and alpha alpha Lambda systems, in terms of a unique set of the baryon-baryon interactions. For the three-range Minnesota force which describes the alpha alpha phase shifts quite accurately, the ground-state and excitation energies of 9Be Lambda are...

  15. Chromopeptides from phycoerythrocyanin. Structure and linkage of the three bilin groups. [Mastigocladus laminosus; Anabaena variabilis

    Energy Technology Data Exchange (ETDEWEB)

    Bishop, J.E.; Rapoport, H.; Klotz, A.V.; Chan, C.F.; Glazer, A.N.; Fueglistaller, P.; Zuber, H.

    1987-01-01

    Phycoerythrocyanin carries two covalently attached phycocyanobilin (PCB) groups on the ..beta.. subunit and a phycobiliviolinoid (PXB) group on the ..cap alpha.. subunit. Three distinct bilipeptides were obtained by proteolytic digestion of this protein: Asn-Gln-Ala-Ala-Cys(PCB)-Ile-Arg, Gly-Asp-Cys(PCB)-Ser-Gln, and Cys(PXB)-Val-Arg. Correlation 500-MHz /sup 1/H NMR analyses showed that the heptapeptide and pentapeptide were attached by cysteinyl thioether linkage to the A ring of the PCB moiety. /sup 1/H NMR and mass spectrometry determinations led to structural assignment for the hitherto uncharacterized PXB moiety, with peptide-thioether bonding possible to either ring A or D. Amino acid sequence homologies strongly favor A-ring linkage.

  16. [Alpha-1 antitrypsin deficiency: diagnosis and treatment].

    Science.gov (United States)

    Camelier, Aquiles A; Winter, Daniel Hugo; Jardim, José Roberto; Barboza, Carlos Eduardo Galvão; Cukier, Alberto; Miravitlles, Marc

    2008-07-01

    Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical implications. Alpha-1 antitrypsin is mainly produced in the liver and acts as an antiprotease. Its principal function is to inactivate neutrophil elastase, preventing tissue damage. The mutation most commonly associated with the clinical disease is the Z allele, which causes polymerization and accumulation within hepatocytes. The accumulation of and the consequent reduction in the serum levels of alpha-1 antitrypsin cause, respectively, liver and lung disease, the latter occurring mainly as early emphysema, predominantly in the lung bases. Diagnosis involves detection of low serum levels of alpha-1 antitrypsin as well as phenotypic confirmation. In addition to the standard treatment of chronic obstructive pulmonary disease, specific therapy consisting of infusion of purified alpha-1 antitrypsin is currently available. The clinical efficacy of this therapy, which appears to be safe, has yet to be definitively established, and its cost-effectiveness is also a controversial issue that is rarely addressed. Despite its importance, in Brazil, there are no epidemiological data on the prevalence of the disease or the frequency of occurrence of deficiency alleles. Underdiagnosis has also been a significant limitation to the study of the disease as well as to appropriate treatment of patients. It is hoped that the creation of the Alpha One International Registry will resolve these and other important issues. PMID:18695797

  17. A COMPARISON BETWEEN SINGLE LINKAGE AND COMPLETE LINKAGE IN AGGLOMERATIVE HIERARCHICAL CLUSTER ANALYSIS FOR IDENTIFYING TOURISTS SEGMENTS

    Directory of Open Access Journals (Sweden)

    Noor Rashidah Rashid

    2012-02-01

    Full Text Available Cluster Analysis is a multivariate method in statistics. Agglomerative Hierarchical Cluster Analysis is one of approaches in Cluster Analysis. There are two linkage methods in Agglomerative Hierarchical Cluster Analysis which are Single Linkage and Complete Linkage. The purpose of this study is to compare between Single Linkage and Complete Linkage in Agglomerative Hierarchical Cluster Analysis. The comparison of performances between these linkage methods was shown by using Kruskal-Wallis test. The result of the comparison used for segmenting tourists of Kapas Island. The statistical software SPSS has been applied to analyze data of this research. The result from Kruskal-Wallis test shows Complete Linkage is more useful in identifying tourists segments. Keywords : Agglomerative Hierarchical Cluster Analysis, Single Linkage, Complete Linkage, Kruskal-Wallis test, tourists

  18. Closed-chain principal vector linkages

    NARCIS (Netherlands)

    Wijk, van der V.; Flores, Paulo; Viadero, Fernando

    2015-01-01

    For high-speed robotics dynamic balance is an important property for low base vibrations and short cycle times. To consider dynamic balance in the beginning of the design process of a manipulator, mechanism solutions can be synthesized from principal vector linkages, which are fundamental kinematic

  19. Regional Workshops on CETA/Educational Linkages.

    Science.gov (United States)

    McGough, Robert; And Others

    This document presents a summary of the proceedings of five regional workshops in Virginia which focused on planning for future involvement and linkages, as well as giving an orientation to the capabilities and operational philosophies of both Comprehensive Employment and Training Act (CETA) programs and educational organizations. Following…

  20. Past CETA Linkages: Models for the Future.

    Science.gov (United States)

    Lapin, Joel D.

    1982-01-01

    Examines lessons learned from successful linkages between community colleges and Comprehensive Employment and Training Act (CETA) sponsors as the basis for future occupational training and employment programs. Reviews research examining CETA funding patterns in California and exemplary arrangements between community colleges and CETA nationwide.…

  1. Whole genome linkage disequilibrium maps in cattle

    Science.gov (United States)

    Bovine whole genome linkage disequilibrium maps were constructed for eight breeds of cattle. These data provide fundamental information concerning bovine genome organization which will allow the design of studies to associate genetic variation with economically important traits and also provides bac...

  2. A Linkage Study in 8 Pakistani Families Segregating as Autosomal Recessive Primary Microcephaly

    Directory of Open Access Journals (Sweden)

    M. Hassanullah

    2011-07-01

    Full Text Available The current study was designed to find the most frequent MCPH phenotype in inbred Pakistani families. Primary microcephaly is marked by small brain size and is usually inherited as recessive trait. In the present study, we performed linkage analysis on 8 Pakistani families with autosomal recessive primary microcephaly (MCPH and linked 6 of them to known MCPH genes/loci like MCPH1 (Microcephalin, MCPH3 (CDK5RAP2 and MCPH5 (ASPM. Majority of the families showed linkage with MCPH5, the most common MCPH locus in Pakistan. The linked families were then subjected to mutational analysis, revealing a previously known G to A transition at nucleotide position 3978 in exon 17 of ASPM gene in three of the families. To decrease its incidence, it is indispensible to train the people of the possible devastating outcome of cousin marriages and to find the carriers through carrier screening programs.

  3. Review of alpha_s determinations

    CERN Document Server

    Pich, Antonio

    2013-01-01

    The present knowledge on the strong coupling is briefly summarized. The most precise determinations of alpha_s, at different energies, are reviewed and compared at the Z mass scale, using the predicted QCD running. The impressive agreement achieved between experimental measurements and theoretical predictions constitutes a beautiful and very significant test of Asymptotic Freedom, establishing QCD as the fundamental theory of the strong interaction. The world average value of the strong coupling is found to be alpha_s(M_Z^2)= 0.1186 \\pm 0.0007.

  4. Genome-wide linkage study of atopic dermatitis in West Highland White Terriers

    Directory of Open Access Journals (Sweden)

    Paps Judith S

    2011-04-01

    Full Text Available Abstract Background Canine atopic dermatitis (AD is a common, heritable, chronic allergic skin condition prevalent in the West Highland White Terrier (WHWT. In canine AD, environmental allergens trigger an inflammatory response causing visible skin lesions and chronic pruritus that can lead to secondary bacterial and yeast infections. The disorder shares many of the clinical and histopathological characteristics of human AD and represents an animal model of this disorder that could be used to further elucidate genetic causes of human AD. Microsatellite markers genotyped in families of WHWTs affected with AD were used to perform a genome-wide linkage study in order to isolate chromosomal regions associated with the disorder. Results Blood samples and health questionnaires were collected from 108 WHWTs spanning three families. A linkage simulation using these 108 dogs showed high power to detect a highly penetrant mutation. Ninety WHWTs were genotyped using markers from the Minimal Screening Set 2 (MSS-2. Two hundred and fifty six markers were informative and were used for linkage analysis. Using a LOD score of 2.7 as a significance threshold, no chromosomal regions were identified with significant linkage to AD. LOD scores greater than 1.0 were located in a 56 cM region of chromosome 7. Conclusions The study was unable to detect any chromosomal regions significantly linked to canine AD. This could be a result of factors such as environmental modification of phenotype, incorrect assignment of phenotype, a mutation of low penetrance, or incomplete genome coverage. A genome-wide SNP association study in a larger cohort of WHWTs may prove more successful by providing higher density coverage and higher statistical power.

  5. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG families

    Directory of Open Access Journals (Sweden)

    Bailey-Wilson Joan E

    2012-06-01

    Full Text Available Abstract Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG. Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD of 1.28, and an allele-sharing lod score (LOD of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM. For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission

  6. Pedimap: Software for the Visualization of Genetic and Phenotypic Data in Pedigrees

    NARCIS (Netherlands)

    Voorrips, R.E.; Bink, M.C.A.M.; Weg, van de W.E.

    2012-01-01

    Pedimap is a user-friendly software tool for visualizing phenotypic and genotypic data for related individuals linked in pedigrees. Genetic data can include marker scores, Identity-by-Descent probabilities, and marker linkage map positions, allowing the visualization of haplotypes through lineages.

  7. The effect of data cleaning on record linkage quality

    OpenAIRE

    Randall, Sean M; Ferrante, Anna M; Boyd, James H.; Semmens, James B

    2013-01-01

    Background Within the field of record linkage, numerous data cleaning and standardisation techniques are employed to ensure the highest quality of links. While these facilities are common in record linkage software packages and are regularly deployed across record linkage units, little work has been published demonstrating the impact of data cleaning on linkage quality. Methods A range of cleaning techniques was applied to both a synthetically generated dataset and a large administrative data...

  8. Genome-wide linkage using the Social Responsiveness Scale in Utah autism pedigrees

    Directory of Open Access Journals (Sweden)

    Coon Hilary

    2010-04-01

    Full Text Available Abstract Background Autism Spectrum Disorders (ASD are phenotypically heterogeneous, characterized by impairments in the development of communication and social behaviour and the presence of repetitive behaviour and restricted interests. Dissecting the genetic complexity of ASD may require phenotypic data reflecting more detail than is offered by a categorical clinical diagnosis. Such data are available from the Social Responsiveness Scale (SRS which is a continuous, quantitative measure of social ability giving scores that range from significant impairment to above average ability. Methods We present genome-wide results for 64 multiplex and extended families ranging from two to nine generations. SRS scores were available from 518 genotyped pedigree subjects, including affected and unaffected relatives. Genotypes from the Illumina 6 k single nucleotide polymorphism panel were provided by the Center for Inherited Disease Research. Quantitative and qualitative analyses were done using MCLINK, a software package that uses Markov chain Monte Carlo (MCMC methods to perform multilocus linkage analysis on large extended pedigrees. Results When analysed as a qualitative trait, linkage occurred in the same locations as in our previous affected-only genome scan of these families, with findings on chromosomes 7q31.1-q32.3 [heterogeneity logarithm of the odds (HLOD = 2.91], 15q13.3 (HLOD = 3.64, and 13q12.3 (HLOD = 2.23. Additional positive qualitative results were seen on chromosomes 6 and 10 in regions that may be of interest for other neuropsychiatric disorders. When analysed as a quantitative trait, results replicated a peak found in an independent sample using quantitative SRS scores on chromosome 11p15.1-p15.4 (HLOD = 2.77. Additional positive quantitative results were seen on chromosomes 7, 9, and 19. Conclusions The SRS linkage peaks reported here substantially overlap with peaks found in our previous affected-only genome scan of clinical diagnosis

  9. Review of alpha_s determinations

    OpenAIRE

    Pich, Antonio

    2013-01-01

    The present knowledge on the strong coupling is briefly summarized. The most precise determinations of alpha_s, at different energies, are reviewed and compared at the Z mass scale, using the predicted QCD running. The impressive agreement achieved between experimental measurements and theoretical predictions constitutes a beautiful and very significant test of Asymptotic Freedom, establishing QCD as the fundamental theory of the strong interaction. The world average value of the strong coupl...

  10. The predominantly nonhydrolytic action of alpha amylases on alpha-maltosyl fluoride.

    Science.gov (United States)

    Okada, G; Genghof, D S; Hehre, E J

    1979-06-01

    Crystalline alpha amylases from a number of sources utilized alpha-maltosyl fluoride as a glycosyl donor and acceptor at high rates (approximately 10 to approximately 1550 mumol/min/mg of protein, for 30 mM substrate). All enzymes catalyzed conversion of this compound into maltooligosaccharides in preference to causing its hydrolysis. Maltotetraosyl flouride and maltooligosaccharides of d.p. 3 to 6+ accounted for 75--93% (by weight) of early reaction-products. At a late stage, the yield of maltooligosaccharides was 2--5 times that of maltose, with chains as long as 12 D-glucosyl residues formed by one amylase (from Asp. oryzae), which utilized alpha-maltosyl fluoride as a donor and as an acceptor at extremely high rates. These results indicate that alpha amylases have a substantial capacity for binding two molecules of this small substrate in a distinctive way, with the C--F glycosylic bond of one and the free C-4 hydroxyl group of the other located in the region of the enzyme's catalytic groups, therby favoring glycosylation of the suitably positioned acceptor over solvent water. Hydrolysis is assumed to prevail when only a single substrate molecule or segment binds to alpha amylase with a (1 linked to 4)-alpha-D-glucosidic linkage of glycosylic C--F bond positioned at the catalytic center. The present demonstration that glycosyl-transfer reactions can be dominantly expressed by alpha amylases, given an appropriate substrate, illustrates the inadequacy of the usual characterization of these enzymes as hydrolases that produce overwhelming hydrolysis of all substrates.

  11. Inhibition of human plasma and serum butyrylcholinesterase (EC 3.1.1.8) by alpha-chaconine and alpha-solanine.

    Science.gov (United States)

    Nigg, H N; Ramos, L E; Graham, E M; Sterling, J; Brown, S; Cornell, J A

    1996-10-01

    The purpose of these experiments was to determine the reversibility of alpha-chaconine and alpha-solanine inhibition of human plasma butyrylcholinesterase (BuChE). For the substrate alpha-naphthylacetate, optimal assay conditions were 0.50 M sodium phosphate buffer and a substrate concentration of 3-5 x 10(-4) M. Dibucaine (1 x 10(-5) M) indicated the usual phenotype for all subjects; alpha-chaconine and alpha-solanine at 2.88 x 10(-6) M inhibited BuChE about 70 and 50%, respectively. One- and 24-hr incubations at 1 x 10(-5) M with alpha-chaconine, alpha-solanine, paraoxon, eserine, and ethanol yielded reversible inhibition with dilution except for paraoxon. Twenty-four-hour dialyses of incubations showed no inhibition except for paraoxon. PAGE enzyme activity gels of 1- and 24-hr incubations also showed no inhibition except for paraoxon. alpha-Chaconine and alpha-solanine are reversible inhibitors of human butyrylcholinesterase. At estimated tissue levels, alpha-chaconine, alpha-solanine, and solanidine inhibited BuChE 10-86%. In assays which combined alpha-chaconine, alpha-solanine, and solanidine, inhibition of BuChE was less than additive. No inhibition of albumin alpha-naphthylacetate esterase (an arylesterase) was noted with any inhibitor. The importance of these data to adverse toxicological effects of potato alkaloids is discussed.

  12. A consensus linkage map of the grass carp (Ctenopharyngodon idella based on microsatellites and SNPs

    Directory of Open Access Journals (Sweden)

    Li Jiale

    2010-02-01

    Full Text Available Abstract Background Grass carp (Ctenopharyngodon idella belongs to the family Cyprinidae which includes more than 2000 fish species. It is one of the most important freshwater food fish species in world aquaculture. A linkage map is an essential framework for mapping traits of interest and is often the first step towards understanding genome evolution. The aim of this study is to construct a first generation genetic map of grass carp using microsatellites and SNPs to generate a new resource for mapping QTL for economically important traits and to conduct a comparative mapping analysis to shed new insights into the evolution of fish genomes. Results We constructed a first generation linkage map of grass carp with a mapping panel containing two F1 families including 192 progenies. Sixteen SNPs in genes and 263 microsatellite markers were mapped to twenty-four linkage groups (LGs. The number of LGs was corresponding to the haploid chromosome number of grass carp. The sex-specific map was 1149.4 and 888.8 cM long in females and males respectively whereas the sex-averaged map spanned 1176.1 cM. The average resolution of the map was 4.2 cM/locus. BLAST searches of sequences of mapped markers of grass carp against the whole genome sequence of zebrafish revealed substantial macrosynteny relationship and extensive colinearity of markers between grass carp and zebrafish. Conclusions The linkage map of grass carp presented here is the first linkage map of a food fish species based on co-dominant markers in the family Cyprinidae. This map provides a valuable resource for mapping phenotypic variations and serves as a reference to approach comparative genomics and understand the evolution of fish genomes and could be complementary to grass carp genome sequencing project.

  13. Genetic locus (stmF) associated with cyclic GMP phosphodiesterase activity in Dictyostelium discoideum maps in linkage group II.

    OpenAIRE

    Coukell, M. B.; Cameron, A M

    1985-01-01

    Previous attempts to map the stmF locus in Dictyostelium discoideum, by using only clone morphology as a marker, have led to equivocal results. Since strains carrying mutations at the stmF locus possess very low cyclic GMP phosphodiesterase activity, we have remapped this locus using both morphological and biochemical markers. Our results indicate that mutations producing a stable "streamer" phenotype and reduced cyclic GMP phosphodiesterase activity are located in linkage group II, probably ...

  14. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits

    OpenAIRE

    Geísa Pinheiro Paes; José Marcelo Soriano Viana; Fabyano Fonseca e Silva; Gabriel Borges Mundim

    2016-01-01

    Abstract The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kerne...

  15. PGC-1alpha Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis

    Directory of Open Access Journals (Sweden)

    Leone Teresa C

    2005-01-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha-/- mice. With age, the PGC-1alpha-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  16. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Teresa C Leone

    2005-04-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha(-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/- mice. With age, the PGC-1alpha(-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  17. Measuring the Success of Wildlife Linkage Efforts

    OpenAIRE

    Servheen, Christopher; Shoemaker, Rebecca; Basting, Pat

    2007-01-01

    Successful movement of wildlife across highways to effectively provide population-level wildlife linkage is usually viewed in one dimension - movement either exists or it does not. We believe that there are multiple ways to measure both the existence and value of such movement opportunities to better demonstrate success or failure of these efforts. The use of multiple methods to measure success will provide quantitative and qualitative values that can be used to better judge the effectiveness...

  18. How Population Growth Affects Linkage Disequilibrium

    OpenAIRE

    Alan R Rogers

    2014-01-01

    The “LD curve” relates the linkage disequilibrium (LD) between pairs of nucleotide sites to the distance that separates them along the chromosome. The shape of this curve reflects natural selection, admixture between populations, and the history of population size. This article derives new results about the last of these effects. When a population expands in size, the LD curve grows steeper, and this effect is especially pronounced following a bottleneck in population size. When a population ...

  19. Manycore Algorithms for Genetic Linkage Analysis

    OpenAIRE

    Medlar, A. J.

    2012-01-01

    Exact algorithms to perform linkage analysis scale exponentially with the size of the input. Beyond a critical point, the amount of work that needs to be done exceeds both available time and memory. In these circumstances, we are forced to either abbreviate the input in some manner or else use an approximation. Approximate methods, like Markov chain Monte Carlo (MCMC), though they make the problem tractable, can take an immense amount of time to converge. The problem of high convergence time ...

  20. Does strong linkage disequilibrium guarantee redundant association results?

    Science.gov (United States)

    Nielsen, Dahlia M; Suchindran, Sunil; Smith, Christopher P

    2008-09-01

    A substantial amount of effort has been expended recently towards the identification and evaluation of tag single nucleotide polymorphisms; markers that, due to linkage disequilibrium (LD) patterns in the genome, are able to act as "proxies" for other polymorphic sites. As such, these tag markers are assumed to capture, on their own, a large proportion of the genetic variation contributed by a much greater number of polymorphic sites. One important consequence of this is the potential ability to reduce the cost of genotyping in an association study without a corresponding loss of power. This application carries an implicit assumption that strong LD between markers implies high correlation between the accompanying association test results, so that once a tag marker is evaluated for association, its outcome will be representative of all the other markers for which it serves as proxy. We examined this assumption directly. We find that in the null hypothesis situation, where there is no association between the markers and the phenotype, the relationship between LD and the correlation between association test outcomes is clear, though it is not always ideal. In the alternative case, when genetic association does exist in the region, the relationship becomes much more complex. Here, reasonably high LD between markers does not necessarily imply that the association test result of one marker is a direct substitute for that of the other. In these cases, eliminating one of these markers from the set to be genotyped in an association study will lead to a reduction in overall power. PMID:18393391

  1. JLIN: A java based linkage disequilibrium plotter

    Directory of Open Access Journals (Sweden)

    McCaskie Pamela A

    2006-02-01

    Full Text Available Abstract Background A great deal of effort and expense are being expended internationally in attempts to detect genetic polymorphisms contributing to susceptibility to complex human disease. Techniques such as Linkage Disequilibrium mapping are being increasingly used to examine and compare markers across increasingly large datasets. Visualisation techniques are becoming essential to analyse the ever-growing volume of data and results available with any given analysis. Results JLIN (Java LINkage disequilibrium plotter is a software package designed for customisable, intuitive visualisation of Linkage Disequilibrium (LD across all common computing platforms. Customisation allows the user to choose particular visualisations, statistical measures and measurement ranges. JLIN also allows the user to export images of the LD visualisation in several common document formats. Conclusion JLIN allows the user to visually compare and contrast the results of a range of statistical measures on the input dataset(s. These measures include the commonly used D' and r2 statistics and empirical p-values. JLIN has a number of unique and novel features that improve on existing LD visualisation tools.

  2. Model-based methods for linkage analysis.

    Science.gov (United States)

    Rice, John P; Saccone, Nancy L; Corbett, Jonathan

    2008-01-01

    The logarithm of an odds ratio (LOD) score method originated in a seminal article by Newton Morton in 1955. The method is broadly concerned with issues of power and the posterior probability of linkage, ensuring that a reported linkage has a high probability of being a true linkage. In addition, the method is sequential so that pedigrees or LOD curves may be combined from published reports to pool data for analysis. This approach has been remarkably successful for 50 years in identifying disease genes for Mendelian disorders. After discussing these issues, we consider the situation for complex disorders where the maximum LOD score statistic shares some of the advantages of the traditional LOD score approach, but is limited by unknown power and the lack of sharing of the primary data needed to optimally combine analytic results. We may still learn from the LOD score method as we explore new methods in molecular biology and genetic analysis to utilize the complete human DNA sequence and the cataloging of all human genes.

  3. Structural synthesis of linkages for quadruped bio-robot legs

    Science.gov (United States)

    Antonescu, O.; Robu, C.; Antonescu, P.

    2016-08-01

    The paper presents a few kinematic schemes of planar mechanisms with bars (linkages) used as part of the quadruped robot legs. The Dunshee linkage having only four elements as crank-rocker mechanism is analyzed. Further, the Klann linkage, which is accomplished by amplifying the crank-rocker mechanism with a dyadic kinematic chain, is also presented. More than that, the Jansen linkage, which is obtained by extending and amplifying the crank-rocker mechanism with two dyadic kinematic chains, is also analyzed. At the end of the paper, the authors present a novel linkage application consisting of a quadric kinematic chain.

  4. New ALPHA-2 magnet

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    On 21 June, members of the ALPHA collaboration celebrated the handover of the first solenoid designed for the ALPHA-2 experiment. The magnet has since been successfully installed and is working well.   Khalid Mansoor, Sumera Yamin and Jeffrey Hangst in front of the new ALPHA-2 solenoid. “This was the first of three identical solenoids that will be installed between now and September, as the rest of the ALPHA-2 device is installed and commissioned,” explains ALPHA spokesperson Jeffrey Hangst. “These magnets are designed to allow us to transfer particles - antiprotons, electrons and positrons - between various parts of the new ALPHA-2 device by controlling the transverse size of the particle bunch that is being transferred.” Sumera Yamin and Khalid Mansoor, two Pakistani scientists from the National Centre for Physics in Islamabad, came to CERN in February specifically to design and manufacture these magnets. “We had the chance to work on act...

  5. beta-Hexosaminidase isozymes from cells cotransfected with alpha and beta cDNA constructs: analysis of the alpha-subunit missense mutation associated with the adult form of Tay-Sachs disease.

    OpenAIRE

    Brown, C. A.; Mahuran, D. J.

    1993-01-01

    In vitro mutagenesis and transient expression in COS cells has been used to associate a missense mutation with a clinical or biochemical phenotype. Mutations affecting the alpha-subunit of beta-hexosaminidase A (alpha beta) (E.C.3.2.1.52) result in Tay-Sachs disease. Because hexosaminidase A is heterodimeric, analysis of alpha-chain mutations is not straightforward. We examine three approaches utilizing previously identified mutations affecting alpha-chain folding. These involve transfection ...

  6. Treatment of Alpha-1 Antitrypsin Deficiency.

    Science.gov (United States)

    Strange, Charlie; Beiko, Tatsiana

    2015-08-01

    Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease that creates multiple unique phenotypes of chronic obstructive pulmonary disease. While bronchospasm, cough, dyspnea, and sputum production all occur with AATD, the phenotypic differences require a computed tomographic (CT) scan to decipher. The availability of augmentation therapy in the United States since 1989 has generated both controversy and evidence that informs the science of usual chronic obstructive pulmonary disease (COPD). Because of the predominance of emphysema in AATD, much of the best evidence concerning biomarkers of emphysema progression comes from this population. Imaging measurement of emphysema progression, impact of emphysema phenotypes on hyperinflation and dynamic hyperinflation, and correlation with traditional spirometric measures of COPD progression are required to understand the impact of AAT therapies. These studies are important for better understanding of usual COPD pathogenesis. Significantly, there are no adequately powered research studies to determine if augmentation therapy is helpful for the non-emphysema phenotypes of AATD. Specifically, phenotypes of chronic bronchitis, asthma predominant disease, and bronchiectasis will require targeted research studies to define optimal therapy. PMID:26238635

  7. Alpha Shapes and Proteins

    DEFF Research Database (Denmark)

    Winter, Pawel; Sterner, Henrik; Sterner, Peter

    2009-01-01

    We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

  8. Genetic linkage of mild pseudoachondroplasia (PSACH) to markers in the pericentromeric region of chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, M.D.; Rasmussen, M.; Garber, P.; Rimoin, D.L.; Cohn, D.H. (Steven Spielberg Pediatric Research Center, Los Angeles, CA (United States)); Weber, J.L. (Marshfield Medical Research Foundation, WI (United States)); Yuen, J.; Reinker, K. (Univ. of Hawaii, Honolulu, HI (United States))

    1993-12-01

    Pseudoachondroplasia (PSACH) is a dominantly inherited form of short-limb dwarfism characterized by dysplastic changes in the spine, epiphyses, and metaphyses and early onset osteoarthropathy. Chondrocytes from affected individuals accumulate an unusual appearing material in the rough endoplasmic reticulum, which has led to the hypothesis that a structural abnormality in a cartilage-specific protein produces the phenotype. The authors recently identified a large family with a mild form of pseudoachondroplasia. By genetic linkage to a dinucleotide repeat polymorphic marker (D19S199), they have localized the disease gene to chromosome 19 (maximum lod score of 7.09 at a recombination fraction of 0.03). Analysis of additional markers and recombinations between the linked markers and the phenotype suggests that the disease gene resides within a 6.3-cM interval in the immediate pericentromeric region of the chromosome. 39 refs., 2 figs., 1 tab.

  9. Targeted Alpha Therapy: From Alpha to Omega

    International Nuclear Information System (INIS)

    This review covers the broad spectrum of Targeted Alpha Therapy (TAT) research in Australia; from in vitro and in vivo studies to clinical trials. The principle of tumour anti-vascular alpha therapy (TAVAT) is discussed in terms of its validation by Monte Carlo calculations of vascular models and the potential role of biological dosimetry is examined. Summmary of this review is as follows: 1. The essence of TAT 2. Therapeutic objectives 3. TAVAT and Monte Carlo microdosimetry 4. Biological dosimetry 5. Preclinical studies 6. Clinical trials 7. What next? 8. Obstacles. (author)

  10. Evidence of linkage of HDL level variation to APOC3 in two samples with different ascertainment.

    Science.gov (United States)

    Gagnon, France; Jarvik, Gail P; Motulsky, Arno G; Deeb, Samir S; Brunzell, John D; Wijsman, Ellen M

    2003-11-01

    The APOA1-C3-A4-A5 gene complex encodes genes whose products are implicated in the metabolism of HDL and/or triglycerides. Although the relationship between polymorphisms in this gene cluster and dyslipidemias was first reported more than 15 years ago, association and linkage results have remained inconclusive. This is due, in part, to the oligogenic and multivariate nature of dyslipidemic phenotypes. Therefore, we investigate evidence of linkage of APOC3 and HDL using two samples of dyslipidemic pedigrees: familial combined hyperlipidemia (FCHL) and isolated low-HDL (ILHDL). We used a strategy that deals with several difficulties inherent in the study of complex traits: by using a Bayesian Markov Chain Monte Carlo (MCMC) approach we allow for oligogenic trait models, as well as simultaneous incorporation of covariates, in the context of multipoint analysis. By using this approach on extended pedigrees we provide evidence of linkage of APOC3 and HDL level variation in two samples with different ascertainment. In addition to APOC3, we estimate that two to three genes, each with a substantial effect on total variance, are responsible for HDL variation in both data sets. We also provide evidence, using the FCHL data set, for a pleiotropic effect between HDL, HDL3 and triglycerides at the APOC3 locus.

  11. Linkage and association of phospholipid transfer protein activity to LASS4.

    Science.gov (United States)

    Rosenthal, Elisabeth A; Ronald, James; Rothstein, Joseph; Rajagopalan, Ramakrishnan; Ranchalis, Jane; Wolfbauer, G; Albers, John J; Brunzell, John D; Motulsky, Arno G; Rieder, Mark J; Nickerson, Deborah A; Wijsman, Ellen M; Jarvik, Gail P

    2011-10-01

    Phospholipid transfer protein activity (PLTPa) is associated with insulin levels and has been implicated in atherosclerotic disease in both mice and humans. Variation at the PLTP structural locus on chromosome 20 explains some, but not all, heritable variation in PLTPa. In order to detect quantitative trait loci (QTLs) elsewhere in the genome that affect PLTPa, we performed both oligogenic and single QTL linkage analysis on four large families (n = 227 with phenotype, n = 330 with genotype, n = 462 total), ascertained for familial combined hyperlipidemia. We detected evidence of linkage between PLTPa and chromosome 19p (lod = 3.2) for a single family and chromosome 2q (lod = 2.8) for all families. Inclusion of additional marker and exome sequence data in the analysis refined the linkage signal on chromosome 19 and implicated coding variation in LASS4, a gene regulated by leptin that is involved in ceramide synthesis. Association between PLTPa and LASS4 variation was replicated in the other three families (P = 0.02), adjusting for pedigree structure. To our knowledge, this is the first example for which exome data was used in families to identify a complex QTL that is not the structural locus.

  12. Buffett’s Alpha

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

    Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

  13. Pattern recognition on brain magnetic resonance imaging in alpha dystroglycanopathies

    Directory of Open Access Journals (Sweden)

    Bindu Parayil

    2010-01-01

    Full Text Available Alpha dystroglycanopathies are heterogeneous group of disorders both phenotypically and genetically. A subgroup of these patients has characteristic brain imaging findings. Four patients with typical imaging findings of alpha dystroglycanopathy are reported. Phenotypic features included: global developmental delay, contractures, hypotonia and oculomotor abnormalities in all. Other manifestations were consanguinity (3, seizures (3, macrocephaly (1, microcephaly (3, retinal changes (2 and hypogenitalism (2. Magnetic resonance imaging (MRI of the brain revealed polymicrogyria, white matter changes, pontine hypoplasia, and subcortical cerebellar cysts in all the patients, ventriculomegaly, callosal abnormalities, and absent septum pellucidum in two and Dandy -Walker variant malformation in three. Magnetic resonace imaging of the first cousin of one the patient had the same characteristic imaging features. Brain imaging findings were almost identical despite heterogeneity in clinical presentation and histopathological features. Pattern recognition of MR imaging features may serve as a clue to the diagnosis of alpha dystroglycanopathy.

  14. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  15. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  16. Alpha-particle diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Young, K.M.

    1991-01-01

    This paper will focus on the state of development of diagnostics which are expected to provide the information needed for {alpha}- physics studies in the future. Conventional measurement of detailed temporal and spatial profiles of background plasma properties in DT will be essential for such aspects as determining heating effectiveness, shaping of the plasma profiles and effects of MHD, but will not be addressed here. This paper will address (1) the measurement of the neutron source, and hence {alpha}-particle birth profile, (2) measurement of the escaping {alpha}-particles and (3) measurement of the confined {alpha}-particles over their full energy range. There will also be a brief discussion of (4) the concerns about instabilities being generated by {alpha}-particles and the methods necessary for measuring these effects. 51 refs., 10 figs.

  17. Imaging alpha particle detector

    Science.gov (United States)

    Anderson, D.F.

    1980-10-29

    A method and apparatus for detecting and imaging alpha particles sources is described. A dielectric coated high voltage electrode and a tungsten wire grid constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source to be quantitatively or qualitatively analyzed. A thin polyester film window allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

  18. Population-environment linkages in international law

    Energy Technology Data Exchange (ETDEWEB)

    Babor, D.D.M.

    1999-03-31

    This article explores population-environment linkages both within developed and developing nations, and considers the consequences of a population growth rate which, as one hectare of arable land is simultaneously lost or destroyed, currently results in eight live births every three seconds. In order to better comprehend the forces governing their perceptions, Part 1 of this article will discuss eight interactive variables which inform decision-making. Part 2 will examine the existence of legal duties under international law to limit or constrain the level of consumption and the right to freely reproduce, particularly as applicable in states considered free of a population problem.

  19. Ethnicity and the ethics of data linkage

    Directory of Open Access Journals (Sweden)

    Boyd Kenneth M

    2007-11-01

    Full Text Available Abstract Linking health data with census data on ethnicity has potential benefits for the health of ethnic minority groups. Ethical objections to linking these data however include concerns about informed consent and the possibility of the findings being misused against the interests of ethnic minority groups. While consent concerns may be allayed by procedures to safeguard anonymity and respect privacy, robust procedures to demonstrate public approval of data linkage also need to be devised. The possibility of findings being misused against the interests of ethnic minority groups may be diminished by informed and open public discussion in mature democracies, but remain a concern in the international context.

  20. Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect

    Energy Technology Data Exchange (ETDEWEB)

    Stine, O.C.; Xu, Jianfeng; McMahon, F.J. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)] [and others

    1995-12-01

    A susceptibility gene on chromosome18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father`s sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; {theta} = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study. 49 refs., 2 figs., 5 tabs.

  1. Clinical features and linkage analysis for a Chinese family with autosomal dominant central areolar choroidal dystrophy

    Institute of Scientific and Technical Information of China (English)

    MA Kai; LIU Ning-pu; YANG Xiu-fen; HAN Cui; ZHANG Ning; XU Jun; LIU Shou-bin; LU Hal; Torkel Snellingen; WANG Ning-li

    2009-01-01

    Background A Chinese family with autosomal dominant central areolar choroidal dystrophy (CACD) was identified.The purpose of this study was to collect the clinical findings from the family and to identify the genetic entity by linkage nalysis.Methods Forty-three individuals from 3 generations of the family underwent ophthalmologic examinations, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. Affected family members further underwent color vision test, color fundus photography,fluorescein angiography, automated perimetry, and electroretinography. The family was followed up for 30 months.Peripheral venous blood or buccal swabs were collected from each family member and genomic DNA was extracted.Linkage analysis was performed for candidate genes or loci using microsatellite markers.Results Seven family members in 3 continuous generations were diagnosed as having autosomal dominant CACD.The family showed progressive development of the disease, affecting both male and female. Age of onset of visual disturbances varied between 11 and 50 years. Phenotypic variability among affected individuals was apparent and ranged from relatively normal-appearing fundus with mild parafoveal pigment mottling to geographic atrophy of the macula. Fluorescein angiography showed hyperfluorescent parafoveal changes in early stage or well-demarcated area of chorioretinal atrophy with enhanced visibility of the residual underlying choroidal vessels in the late stage. Peripheral retina and visual fields were normal in affected individuals. Electroretinogram showed normal or mild reduction in the photopic amplitude. Eight candidate genes (STGD4, RCD1, peripherin/RDS, GUCA1A, RIMS1, UNC119, GUC Y2D, and AIPL1) and two genetic loci (4p15.2-16.3, and 17p13) were excluded to be responsible for the disease by linkage analysis.Conclusions The clinical findings of this Chinese family with CACD shared

  2. Systematic, genome-wide, sex-specific linkage of cardiovascular traits in French Canadians.

    Science.gov (United States)

    Seda, Ondrej; Tremblay, Johanne; Gaudet, Daniel; Brunelle, Pierre-Luc; Gurau, Alexandru; Merlo, Ettore; Pilote, Louise; Orlov, Sergei N; Boulva, Francis; Petrovich, Milan; Kotchen, Theodore A; Cowley, Allen W; Hamet, Pavel

    2008-04-01

    The sexual dimorphism of cardiovascular traits, as well as susceptibility to a variety of related diseases, has long been recognized, yet their sex-specific genomic determinants are largely unknown. We systematically assessed the sex-specific heritability and linkage of 539 hemodynamic, metabolic, anthropometric, and humoral traits in 120 French-Canadian families from the Saguenay-Lac-St-Jean region of Quebec, Canada. We performed multipoint linkage analysis using microsatellite markers followed by peak-wide linkage scan based on Affymetrix Human Mapping 50K Array Xba240 single nucleotide polymorphism genotypes in 3 settings, including the entire sample and then separately in men and women. Nearly one half of the traits were age and sex independent, one quarter were both age and sex dependent, and one eighth were exclusively age or sex dependent. Sex-specific phenotypes are most frequent in heart rate and blood pressure categories, whereas sex- and age-independent determinants are predominant among humoral and biochemical parameters. Twenty sex-specific loci passing multiple testing criteria were corroborated by 2-point single nucleotide polymorphism linkage. Several resting systolic blood pressure measurements showed significant genotype-by-sex interaction, eg, male-specific locus at chromosome 12 (male-female logarithm of odds difference: 4.16; interaction P=0.0002), which was undetectable in the entire population, even after adjustment for sex. Detailed interrogation of this locus revealed a 220-kb block overlapping parts of TAO-kinase 3 and SUDS3 genes. In summary, a large number of complex cardiovascular traits display significant sexual dimorphism, for which we have demonstrated genomic determinants at the haplotype level. Many of these would have been missed in a traditional, sex-adjusted setting.

  3. The alpha channeling effect

    Energy Technology Data Exchange (ETDEWEB)

    Fisch, N. J.

    2015-12-10

    Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a way that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.

  4. Alpha thalassaemia-mental retardation, X linked

    Directory of Open Access Journals (Sweden)

    Gibbons Richard

    2006-05-01

    Full Text Available Abstract X-linked alpha thalassaemia mental retardation (ATR-X syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal. So far, 168 patients have been reported. Language is usually very limited. Seizures occur in about one third of the cases. While many patients are affectionate with their caregivers, some exhibit autistic-like behaviour. Patients present with facial hypotonia and a characteristic mouth. Genital abnormalities are observed in 80% of children and range from undescended testes to ambiguous genitalia. Alpha-thalassaemia is not always present. This syndrome is X-linked recessive and results from mutations in the ATRX gene. This gene encodes the widely expressed ATRX protein. ATRX mutations cause diverse changes in the pattern of DNA methylation at heterochromatic loci but it is not yet known whether this is responsible for the clinical phenotype. The diagnosis can be established by detection of alpha thalassaemia, identification of ATRX gene mutations, ATRX protein studies and X-inactivation studies. Genetic counselling can be offered to families. Management is multidisciplinary: young children must be carefully monitored for gastro-oesophageal reflux as it may cause death. A number of individuals with ATR-X are fit and well in their 30s and 40s.

  5. Constructing Linkage Disequilibrium Map with Iterative Approach

    Science.gov (United States)

    Ao, S. I.

    2008-05-01

    With recent advance of the genotyping single nucleotide polymorphisms (SNPs) in mass scale of high density in a candidate region of the human genome, the linkage disequilibrium analysis can offer a much higher resolution of the biological samples than the traditional linkage maps. We have formulated this LD mapping problem as a constrained unidimensional scaling problem. Our method, which is directly based on the measurement of LD among SNPs, is non-parametric. Therefore it is different from LD maps derived from the given Malecot model. We have formulated with the quadratic programming approach for solving this constrained unidimensional scaling problem. Different from the classical metric unidimensional scaling problem, the constrained problem is not an NP-hard combinatorial problem. The optimal solution is determined by using the quadratic programming solver. Nevertheless, because of the large requirement for memory during the running time that may cause the out of memory problems, and the high computational time of the quadratic programming algorithm, the iterative algorithm has been developed for solving this LD constrained unidimensional scaling problem.

  6. Mechanical Design of Step-Climbing Vehicle with Passive Linkages

    OpenAIRE

    Chugo, Daisuke; Kawabata, Kuniaki; Kaetsu, Hayato; Asama, Hajime; Mishima, Taketoshi

    2007-01-01

    In this paper, we proposed the mechanical design for passive linkages. We discuss the moment force which is applied on the vehicle body when the vehicle contacts the step and we derive the moment force using the position of free joint point. From the derivation, we design new passive linkage mechanism and utilize it to our prototype. We verified the effectiveness of our proposed design on passive linkages by computer simulations and experiments. Utilizing our proposed mechanical design on the...

  7. Molecular Cytogenetic Maps of Sorghum Linkage Groups 2 and 8

    OpenAIRE

    Kim, Jeong-Soon; Klein, Patricia E; Klein, Robert R.; Price, H. James; Mullet, John E.; Stelly, David M.

    2005-01-01

    To integrate genetic, physical, and cytological perspectives of the Sorghum bicolor genome, we selected 40 landed bacterial artificial chromosome (BAC) clones that contain different linkage map markers, 21 from linkage group 2 (LG-02) and 19 from linkage group 8 (LG-08). Multi-BAC probe cocktails were constructed for each chromosome from the landed BACs, which were also preevaluated for FISH signal quality, relative position, and collective chromosome coverage. Comparison to the corresponding...

  8. A genetic combination of silent beta-thalassaemia, high Hb A2 beta-thalassaemia, and single alpha globin gene deletion causing mild thalassaemia intermedia.

    OpenAIRE

    R. Galanello; Maccioni, L; ROSATELLI, M. C.; Ibba, P; Nurchi, A M; Cao, A

    1984-01-01

    This paper reports a Sardinian patient, who was a compound heterozygote for silent beta-thalassaemia and high Hb A2 beta o-thalassaemia with the clinical phenotype of mild thalassaemia intermedia; alpha globin gene mapping showed a single alpha globin gene deletion. The reduced alpha globin chain output resulted in more balanced globin chain synthesis, which in turn accounted for the mild clinical phenotype.

  9. Automated Generation of Kempe Linkage and Its Complexity

    Institute of Scientific and Technical Information of China (English)

    高小山; 朱长才

    1999-01-01

    It is a famous result of Kempe that a linkage can be designed to generate any given plane algebraic curve.In this paper,Kempe's result is improved to give a precise algorithm for generating Kempe linkage.We proved that for an algebraic plane curve of degrenn n,Kempe linkage uses at most O(n4) links.Efforts to implement a program which may generate Kempe linkage and simulation of the generation process of the plane curves are presented in the paper.

  10. ECONOMIC GROWTH AND SECTORAL LINKAGES: EMPIRICAL EVIDENCE FROM ODISHA

    OpenAIRE

    Behera, Deepak Kumar

    2012-01-01

    The present paper analyses the trends in sectoral shares in state domestic product and inter-sectoral linkages in Odisha for the period 1980-81 to 2011-12. Results drawn from Granger causality test suggest that there is a weak linkage between primary and secondary sectors in the growth process. In the case of primary and tertiary sector services, though the primary sector does not show linkages with the tertiary sector as a whole, it does have linkages with some important sub-services like tr...

  11. Quantitative linkage analysis to the autism endophenotype social responsiveness identifies genome-wide significant linkage to two regions on chromosome 8

    Science.gov (United States)

    Lowe, Jennifer K.; Werling, Donna M.; Constantino, John N.; Cantor, Rita M.; Geschwind, Daniel H.

    2015-01-01

    Objective Autism Spectrum Disorder (ASD) is characterized by deficits in social function and the presence of repetitive and restrictive behaviors. Following a previous test of principle, we adopted a quantitative approach to discovering genes contributing to the broader autism phenotype by using social responsiveness as an endophenotype for ASD. Method Linkage analyses using scores from the Social Responsiveness Scale (SRS) were performed in 590 families from AGRE, a largely multiplex ASD cohort. Regional and genome-wide association analyses were performed to search for common variants contributing to social responsiveness. Results SRS is unimodally distributed in male offspring from multiplex autism families, in contrast with a bimodal distribution observed in females. In correlated analyses differing by SRS respondent, genome-wide significant linkage for social responsiveness was identified at chr8p21.3 (multi-point LOD=4.11; teacher/parent scores) and chr8q24.22 (multi-point LOD=4.54; parent-only scores), respectively. Genome-wide or linkage-directed association analyses did not detect common variants contributing to social responsiveness. Conclusions The sex-differential distributions of SRS in multiplex autism families likely reflect mechanisms contributing to the sex ratio for autism observed in the general population and form a quantitative signature of reduced penetrance of inherited liability to ASD among females. The identification of two strong loci for social responsiveness validates the endophenotype approach for the identification of genetic variants contributing to complex traits such as ASD. While causal mutations have yet to be identified, these findings are consistent with segregation of rare genetic variants influencing social responsiveness and underscore the increasingly recognized role of rare inherited variants in the genetic architecture of ASD. PMID:25727539

  12. Jagged 1 Rescues the Duchenne Muscular Dystrophy Phenotype.

    Science.gov (United States)

    Vieira, Natassia M; Elvers, Ingegerd; Alexander, Matthew S; Moreira, Yuri B; Eran, Alal; Gomes, Juliana P; Marshall, Jamie L; Karlsson, Elinor K; Verjovski-Almeida, Sergio; Lindblad-Toh, Kerstin; Kunkel, Louis M; Zatz, Mayana

    2015-11-19

    Duchenne muscular dystrophy (DMD), caused by mutations at the dystrophin gene, is the most common form of muscular dystrophy. There is no cure for DMD and current therapeutic approaches to restore dystrophin expression are only partially effective. The absence of dystrophin in muscle results in dysregulation of signaling pathways, which could be targets for disease therapy and drug discovery. Previously, we identified two exceptional Golden Retriever muscular dystrophy (GRMD) dogs that are mildly affected, have functional muscle, and normal lifespan despite the complete absence of dystrophin. Now, our data on linkage, whole-genome sequencing, and transcriptome analyses of these dogs compared to severely affected GRMD and control animals reveals that increased expression of Jagged1 gene, a known regulator of the Notch signaling pathway, is a hallmark of the mild phenotype. Functional analyses demonstrate that Jagged1 overexpression ameliorates the dystrophic phenotype, suggesting that Jagged1 may represent a target for DMD therapy in a dystrophin-independent manner. PAPERCLIP. PMID:26582133

  13. Local versus nonlocal $\\alpha\\alpha$ interactions in $3\\alpha$ description of $^{12}$C

    CERN Document Server

    Suzuki, Y; Descouvemont, P; Fujiwara, Y; Matsumura, H; Orabi, M; Theeten, M

    2008-01-01

    Local $\\alpha \\alpha$ potentials fail to describe $^{12}$C as a $3\\alpha$ system. Nonlocal $\\alpha \\alpha$ potentials that renormalize the energy-dependent kernel of the resonating group method allow interpreting simultaneously the ground state and $0^+_2$ resonance of $^{12}$C as $3\\alpha$ states. A comparison with fully microscopic calculations provides a measure of the importance of three-cluster exchanges in those states.

  14. Bremsstrahlung in $\\alpha$ Decay

    CERN Document Server

    Takigawa, N; Hagino, K; Ono, A; Brink, D M

    1999-01-01

    A quantum mechanical analysis of the bremsstrahlung in $\\alpha$ decay of $^{210}$Po is performed in close reference to a semiclassical theory. We clarify the contribution from the tunneling, mixed, outside barrier regions and from the wall of the inner potential well to the final spectral distribution, and discuss their interplay. We also comment on the validity of semiclassical calculations, and the possibility to eliminate the ambiguity in the nuclear potential between the alpha particle and daughter nucleus using the bremsstrahlung spectrum.

  15. Amino-acid substitution in alpha-spectrin commonly coinherited with nondominant hereditary spherocytosis.

    Science.gov (United States)

    Tse, W T; Gallagher, P G; Jenkins, P B; Wang, Y; Benoit, L; Speicher, D; Winkelmann, J C; Agre, P; Forget, B G; Marchesi, S L

    1997-03-01

    Nondominant hereditary spherocytosis (ndHS) is a disorder characterized in some patients by severe hemolytic anemia and marked deficiency of erythrocyte spectrin. This report describes the identification of a variant spectrin chain, alpha-spectrin Bughill or alpha(BH), that is associated with this disorder in a number of patients. Tryptic maps of spectrin from affected individuals revealed an acidic shift in isoelectric point of the alphaII domain peptides at 46 kD and 35 kD. A point mutation at codon 970 of the alpha-spectrin gene (GCT-->GAT), that changes the encoded amino acid from an alanine to an aspartic acid, was identified in genomic DNA of affected patients. The alpha(BH) variant was present in 8 patients with ndHS from five different kindreds but was absent in 4 patients from two other kindreds. The 8 ndHS patients with the alpha(BH) variant appeared to be homozygous for the alpha(BH) variant by analysis of peptide maps of limited tryptic digests of erythrocyte spectrin. However, following genomic DNA analysis, only 2 of these patients were true homozygotes, whereas 6 were found to be doubly heterozygous for the alpha(BH) allele and a second, presumably abnormal, alpha-spectrin gene. These results suggest that, in these 6 patients, the second alpha-spectrin allele is in fact associated with one or more genetic defect(s), causing decreased accumulation of alpha-spectrin. The pattern of transmission of the alpha(BH) allele in certain families suggests that the alpha(BH) amino-acid substitution is not itself responsible for ndHS but is more likely a polymorphic variant that, in some but not all cases, is in linkage disequilibrium with another uncharacterized alpha-spectrin gene defect that itself is a cause of ndHS. PMID:9067503

  16. Localization, by linkage analysis, of the cystinuria type III gene to chromosome 19q13.1

    Energy Technology Data Exchange (ETDEWEB)

    Bisceglia, L.; Totaro, A.; Melchionda, S. [and others

    1997-03-01

    Cystinuria is an autosomal recessive aminoaciduria in which three urinary phenotypes (I, II, and III) have been described. An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. Mutational and linkage analysis demonstrated the presence of genetic heterogeneity in which the SLC3A1 gene is responsible for type I cystinuria but not for type II or type III. In this study, we report the identification of the cystinuria type III locus on the long arm of chromosome 19 (19q13.1), obtained after a genomewide search. Pairwise linkage analysis in a series of type III or type II families previously excluded from linkage to the cystinuria type I locus (SLC3A1 gene) revealed a significant maximum LOD score (Z{sub max}) of 13.11 at a maximum recombination fraction ({theta}{sub max}) of .00, with marker D19S225. Multipoint linkage analysis performed with the use of additional markers from the region placed the cystinuria type III locus between D19S414 and D19S220. Preliminary data on type II families also seem to place the disease locus for this rare type of cystinuria at 19q13.1 (significant Z{sub max} = 3.11 at {theta}{sub max} of .00, with marker D19S225). 33 refs., 2 figs., 1 tab.

  17. ALPHA-2: the sequel

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    While many experiments are methodically planning for intense works over the long shutdown, there is one experiment that is already working at full steam: ALPHA-2. Its final components arrived last month and will completely replace the previous ALPHA set-up. Unlike its predecessor, this next generation experiment has been specifically designed to measure the properties of antimatter.   The ALPHA team lower the new superconducting solenoid magnet into place. The ALPHA collaboration is working at full speed to complete the ALPHA-2 set-up for mid-November – this will give them a few weeks of running before the AD shutdown on 17 December. “We really want to get some experience with this device this year so that, if we need to make any changes, we will have time during the long shutdown in which to make them,” says Jeffrey Hangst, ALPHA spokesperson. “Rather than starting the 2014 run in the commissioning stage, we will be up and running from the get go.&...

  18. Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression

    Directory of Open Access Journals (Sweden)

    Hasegawa Shunsuke

    2009-03-01

    Full Text Available Abstract Background Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII in learning, memory and long-term potentiation (LTP. However, previous studies have also shown that alpha-CaMKII (+/- heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes. Results We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/- heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression. Conclusion Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects

  19. Linkage of PRA models. Phase 1, Results

    International Nuclear Information System (INIS)

    The goal of the Phase I work of the ''Linkage of PRA Models'' project was to postulate methods of providing guidance for US Nuclear Regulator Commission (NRC) personnel on the selection and usage of probabilistic risk assessment (PRA) models that are best suited to the analysis they are performing. In particular, methods and associated features are provided for (a) the selection of an appropriate PRA model for a particular analysis, (b) complementary evaluation tools for the analysis, and (c) a PRA model cross-referencing method. As part of this work, three areas adjoining ''linking'' analyses to PRA models were investigated: (a) the PRA models that are currently available, (b) the various types of analyses that are performed within the NRC, and (c) the difficulty in trying to provide a ''generic'' classification scheme to groups plants based upon a particular plant attribute

  20. The Barley Chromosome 5 Linkage Map

    DEFF Research Database (Denmark)

    Jensen, J.; Jørgensen, Jørgen Helms

    1975-01-01

    The literature is surveyed for data on recombination between loci on chromosome 5 of barley; 13 loci fall into the category “mapped” loci, more than 20 into the category “associated” loci and nine into the category “loci once suggested to be on chromosome 5”. A procedure was developed...... for estimating a linkage map; it involves (1) transformation by the Kosambi mapping function of the available recombination percentages to additive map distances, (2) calculations of a set of map distances from the transformed recombination percentages by a maximum likelihood method in which all the available...... data are utilized jointly, and (3) omission of inconsistent data and determination of the most likely order of the loci. This procedure was applied to the 42 recombination percentages available for the 13 “mapped” loci. Due to inconsistencies 14 of the recombination percentages and, therefore, two...

  1. Resting alpha activity predicts learning ability in alpha neurofeedback

    OpenAIRE

    Wenya eNan; Feng eWan; Mang I eVai; Agostinho eRosa

    2014-01-01

    Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the tr...

  2. Mass spectrometry and /sup 13/C nuclear magnetic resonance spectroscopy of compounds modeling the glycopeptide linkage of glycoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Blumberg, K.; Bush, C.A.

    1982-01-15

    The properties of several compounds useful as models for three-dimensional conformational studies and the investigation of the chemical degradation of glycopeptide linkages both of the N- and O-glycosidic type are described. Using the method of differential chemical shift in H/sub 2/O and D/sub 2/O as solvents, the carbon NMR spectrum of N-acetylglucosaminylasparagine, 1-N-acetyl-..beta..-D-glucopyranosylamine, and 1-N-acetyl-2-acetamido-..beta..-D-glycopyranosylamine has been assigned. Electron impact mass spectra of the peracetylated derivatives of the latter two compounds show a peak apparently unique to glycopyranosylamides at m/e = 269, no analog of which is observed in the mass spectra of other peracetylated sugars. As models of the ..cap alpha..-O-glycosidic linkage, fully assigned carbon NMR spectra of ..cap alpha..-methyl-N-acetylgalactosamine (GalNAc), ..cap alpha..-methyl-3-O-methyl GalNAc, and -GlcNAc as well as the disaccharide Glc-..beta..-l ..-->.. 3 GalNAc are reported. Because certain anomalies in the chemical shifts and /sup 1/J/sub CH/ observed in the disaccharide and in O-glycosylated glycoproteins are not observed in the simple model compounds, they may result from conformational interactions in the glycopeptides.

  3. Alpha particles in fusion research

    International Nuclear Information System (INIS)

    This collection of 39 (mostly view graph) presentations addresses various aspects of alpha particle physics in thermonuclear fusion research, including energy balance and alpha particle losses, transport, the influence of alpha particles on plasma stability, helium ash, the transition to and sustainment of a burning fusion plasma, as well as alpha particle diagnostics. Refs, figs and tabs

  4. Fine mapping of multiple interacting quantitative trait loci using combined linkage disequilibrium and linkage information

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Quantitative trait loci (QTL) and their additive, dominance and epistatic effects play a critical role in complex trait variation. It is often infeasible to detect multiple interacting QTL due to main effects often being confounded by interaction effects.Positioning interacting QTL within a small region is even more difficult. We present a variance component approach nested in an empirical Bayesian method, which simultaneously takes into account additive, dominance and epistatic effects due to multiple interacting QTL. The covariance structure used in the variance component approach is based on combined linkage disequilibrium and linkage (LDL) information. In a simulation study where there are complex epistatic interactions between QTL, it is possible to simultaneously fine map interacting QTL using the proposed approach. The present method combined with LDL information can efficiently detect QTL and their dominance and epistatic effects, making it possible to simultaneously fine map main and epistatic QTL.

  5. SYNTHESIS OF GUIDED CHAIN DRIVE MECHANISM WITH LINKAGE

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    A method of designing guided chain drive mechanism with linkage basing on the given motion track is expounded. The method consists of two steps that are synthesizing four-bar linkage approximately first and then deducing guide track, removing crank and jointing free end with chain. An example of synthesis that can realize the given motion track precisely is provided.

  6. Urban-rural linkages enhancing European territorial competitiveness: background paper

    OpenAIRE

    Davidson, Gill

    2008-01-01

    This background paper provides the context for the seminar on urban-rural linkages enhancing European territorial competitiveness, to be held by DG REGIO on 17th September 2008. This seminar forms part of an ongoing debate at European level on the importance of urban-rural linkages for territorial competitiveness, and on appropriate support mechanisms to assist these developments in Member States.

  7. A microsatellite genetic linkage map of black rockfish ( Sebastes schlegeli)

    Science.gov (United States)

    Chu, Guannan; Jiang, Liming; He, Yan; Yu, Haiyang; Wang, Zhigang; Jiang, Haibin; Zhang, Quanqi

    2014-12-01

    Ovoviviparous black rockfish ( Sebastes schlegeli) is an important marine fish species for aquaculture and fisheries in China. Genetic information of this species is scarce because of the lack of microsatellite markers. In this study, a large number of microsatellite markers of black rockfish were isolated by constructing microsatellite-enriched libraries. Female- and male-specific genetic linkage maps were constructed using 435 microsatellite markers genotyped in a full-sib family of the fish species. The female linkage map contained 140 microsatellite markers, in which 23 linkage groups had a total genetic length of 1334.1 cM and average inter-marker space of 13.3 cM. The male linkage map contained 156 microsatellite markers, in which 25 linkage groups had a total genetic length of 1359.6 cM and average inter-marker distance of 12.4 cM. The genome coverage of the female and male linkage maps was 68.6% and 69.3%, respectively. The female-to-male ratio of the recombination rate was approximately 1.07:1 in adjacent microsatellite markers. This paper presents the first genetic linkage map of microsatellites in black rockfish. The collection of polymorphic markers and sex-specific linkage maps of black rockfish could be useful for further investigations on parental assignment, population genetics, quantitative trait loci mapping, and marker-assisted selection in related breeding programs.

  8. Privacy-preserving record linkage on large real world datasets.

    Science.gov (United States)

    Randall, Sean M; Ferrante, Anna M; Boyd, James H; Bauer, Jacqueline K; Semmens, James B

    2014-08-01

    Record linkage typically involves the use of dedicated linkage units who are supplied with personally identifying information to determine individuals from within and across datasets. The personally identifying information supplied to linkage units is separated from clinical information prior to release by data custodians. While this substantially reduces the risk of disclosure of sensitive information, some residual risks still exist and remain a concern for some custodians. In this paper we trial a method of record linkage which reduces privacy risk still further on large real world administrative data. The method uses encrypted personal identifying information (bloom filters) in a probability-based linkage framework. The privacy preserving linkage method was tested on ten years of New South Wales (NSW) and Western Australian (WA) hospital admissions data, comprising in total over 26 million records. No difference in linkage quality was found when the results were compared to traditional probabilistic methods using full unencrypted personal identifiers. This presents as a possible means of reducing privacy risks related to record linkage in population level research studies. It is hoped that through adaptations of this method or similar privacy preserving methods, risks related to information disclosure can be reduced so that the benefits of linked research taking place can be fully realised.

  9. Building and Strengthening Linkages between CETA and Community Colleges.

    Science.gov (United States)

    Lapin, Joel D.

    A study was conducted by Catonsville Community College (Maryland) to identify those factors that foster successful linkages between Comprehensive Employment and Training Act (CETA) sponsors and community colleges. The study involved: (1) identifying exemplary CETA/college linkages through consultation with experts in academe and government; (2)…

  10. Creative Activities in Music – A Genome-Wide Linkage Analysis

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  11. Joint QTL linkage mapping for multiple-cross mating design sharing one common parent.

    Directory of Open Access Journals (Sweden)

    Huihui Li

    Full Text Available BACKGROUND: Nested association mapping (NAM is a novel genetic mating design that combines the advantages of linkage analysis and association mapping. This design provides opportunities to study the inheritance of complex traits, but also requires more advanced statistical methods. In this paper, we present the detailed algorithm of a QTL linkage mapping method suitable for genetic populations derived from NAM designs. This method is called joint inclusive composite interval mapping (JICIM. Simulations were designed on the detected QTL in a maize NAM population and an Arabidopsis NAM population so as to evaluate the efficiency of the NAM design and the JICIM method. PRINCIPAL FINDINGS: Fifty-two QTL were identified in the maize population, explaining 89% of the phenotypic variance of days to silking, and nine QTL were identified in the Arabidopsis population, explaining 83% of the phenotypic variance of flowering time. Simulations indicated that the detection power of these identified QTL was consistently high, especially for large-effect QTL. For rare QTL having significant effects in only one family, the power of correct detection within the 5 cM support interval was around 80% for 1-day effect QTL in the maize population, and for 3-day effect QTL in the Arabidopsis population. For smaller-effect QTL, the power diminished, e.g., it was around 50% for maize QTL with an effect of 0.5 day. When QTL were linked at a distance of 5 cM, the likelihood of mapping them as two distinct QTL was about 70% in the maize population. When the linkage distance was 1 cM, they were more likely mapped as one single QTL at an intermediary position. CONCLUSIONS: Because it takes advantage of the large genetic variation among parental lines and the large population size, NAM is a powerful multiple-cross design for complex trait dissection. JICIM is an efficient and specialty method for the joint QTL linkage mapping of genetic populations derived from the NAM design.

  12. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  13. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Directory of Open Access Journals (Sweden)

    Jaana Oikkonen

    Full Text Available Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases, 4q22.1 for composing (LOD 2.15, 103 cases and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases. Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA at 18q21 (LOD 3.09, 149 cases, which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD, which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We

  14. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    Science.gov (United States)

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  15. Trafficking of. cap alpha. -L-fucosidase in lymphoid cells

    Energy Technology Data Exchange (ETDEWEB)

    DiCioccio, R.A.; Brown, K.S.

    1987-05-01

    The quantity of ..cap alpha..-L-fucosidase in human serum is determined by heredity. The mechanism controlling levels of the enzyme in serum is unknown. To investigate this, lymphoid cell lines derived from individuals with either low, intermediate or high ..cap alpha..-L-fucosidase in serum were established. Steady state levels of extracellular ..cap alpha..-L-fucosidase protein and activity overlapped among the cell lines. Thus, in vivo serum phenotypes of ..cap alpha..-L-fucosidase are not adequately expressed in this system. ..cap alpha..-L-Fucosidase was also metabolically labelled with /sup 35/S-methionine, immunoprecipitated, and examined by SDS-PAGE. Cells pulse-labelled from 0.25-2 h had a major intracellular form of enzyme (Mr = 58,000). Cells pulsed for 1.5 h and chased for 21 h with unlabeled methionine had an intracellular form of Mr = 60,000 and an extracellular form of Mr = 62,000. Cells treated with chloroquine had only the 58,000-form both intra- and extra-cellularly. Moreover, chloroquine did not effect the quantitative distribution of ..cap alpha..-L-fucosidase between cells and medium. In fibroblasts, chloroquine enhanced the secretion of newly made lysosomal enzymes and blocked the processing of intercellular enzyme forms from a higher to a lower molecular mass. Thus, there are trafficking differences between ..cap alpha..-L-fucosidase in lymphoid cells and lysosomal enzymes in fibroblasts. This suggests that alternative targeting mechanisms for lysosomal enzymes exist in these cells.

  16. Construction variants for linkage of overcast combinations - part 2

    Energy Technology Data Exchange (ETDEWEB)

    Goehring, H.

    1988-04-01

    Continues the review of linkage designs between bucket wheel excavators and boom spreaders in surface mine overburden removal. Boom linkage with three linkage points comes in two versions, with and without auxiliary boom support. The TAKRAF manufacturer's ARs 8800.195 spreader with suspended receiving boom and no auxiliary support crawler on which the boom may rest is given as an example. The version with three linkage points incorporating an auxiliary boom support crawler is further explained. This version (SRs 1400 bucket wheel excavator combined with ARs 5200.165.spreader) operates at the Visonta coal surface mine in Hungary. Boom linkage at four points is outlined as a further technological possibility. This design requires an additional mobile transfer conveyor between excavator and spreader, rather than an auxiliary support crawler. This version is preferred in surface mines with a large distance between excavator and spreader or where equipment must be positioned on different mine bench levels. 2 refs.

  17. Automated assembly of oligosaccharides containing multiple cis-glycosidic linkages

    Science.gov (United States)

    Hahm, Heung Sik; Hurevich, Mattan; Seeberger, Peter H.

    2016-09-01

    Automated glycan assembly (AGA) has advanced from a concept to a commercial technology that rapidly provides access to diverse oligosaccharide chains as long as 30-mers. To date, AGA was mainly employed to incorporate trans-glycosidic linkages, where C2 participating protecting groups ensure stereoselective couplings. Stereocontrol during the installation of cis-glycosidic linkages cannot rely on C2-participation and anomeric mixtures are typically formed. Here, we demonstrate that oligosaccharides containing multiple cis-glycosidic linkages can be prepared efficiently by AGA using monosaccharide building blocks equipped with remote participating protecting groups. The concept is illustrated by the automated syntheses of biologically relevant oligosaccharides bearing various cis-galactosidic and cis-glucosidic linkages. This work provides further proof that AGA facilitates the synthesis of complex oligosaccharides with multiple cis-linkages and other biologically important oligosaccharides.

  18. Genetic analysis of the estrogen-related receptor alpha and studies of association with obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Larsen, L H; Rose, C S; Sparsø, T;

    2007-01-01

    The estrogen-related receptor alpha (ERRalpha or NR3B1) is a transcription factor from the nuclear receptor super-family, group III. The gene encoding ERRalpha (ESRRA) is located on chromosome 11q13, a region showing genetic linkage to body mass index and fat percentage. Through interaction...

  19. Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait

    DEFF Research Database (Denmark)

    Huyghe, J.R.; Laer, L. Van; Hendrickx, J.J.;

    2008-01-01

    conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were...... results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We...... detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait Udgivelsesdato: 2008/9/12...

  20. [MapDraw: a microsoft excel macro for drawing genetic linkage maps based on given genetic linkage data].

    Science.gov (United States)

    Liu, Ren-Hu; Meng, Jin-Ling

    2003-05-01

    MAPMAKER is one of the most widely used computer software package for constructing genetic linkage maps.However, the PC version, MAPMAKER 3.0 for PC, could not draw the genetic linkage maps that its Macintosh version, MAPMAKER 3.0 for Macintosh,was able to do. Especially in recent years, Macintosh computer is much less popular than PC. Most of the geneticists use PC to analyze their genetic linkage data. So a new computer software to draw the same genetic linkage maps on PC as the MAPMAKER for Macintosh to do on Macintosh has been crying for. Microsoft Excel,one component of Microsoft Office package, is one of the most popular software in laboratory data processing. Microsoft Visual Basic for Applications (VBA) is one of the most powerful functions of Microsoft Excel. Using this program language, we can take creative control of Excel, including genetic linkage map construction, automatic data processing and more. In this paper, a Microsoft Excel macro called MapDraw is constructed to draw genetic linkage maps on PC computer based on given genetic linkage data. Use this software,you can freely construct beautiful genetic linkage map in Excel and freely edit and copy it to Word or other application. This software is just an Excel format file. You can freely copy it from ftp://211.69.140.177 or ftp://brassica.hzau.edu.cn and the source code can be found in Excel's Visual Basic Editor. PMID:15639879

  1. Confirmation of linkage of Best`s macular dystrophy to 11q13, and evidence for genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Mansergh, F.C.; Kenna, P.F.; Farrar, G.J. [Trinity College, Dublin (United Kingdom)] [and others

    1994-09-01

    Best`s macular dystrophy, also known as vitelliform macular degeneration, is an autosomal dominant, early onset form of macular degeneration. The disease is characterized by a roughly circular deposit of lipofuscin beneath the pigment epithelium of the retinal macula. Linkage studies were performed in two families, one Irish and one German, segregating typical Best`s macular dystrophy. In the Irish family (BTMD1), linkage analysis mapped the disease causing gene to chromosome 11q13, in a 10 cM region between the microsatellite markers PYGM and D11S871. Both markers showed different recombinants with the disease phenotype. This is a region that has previously shown linkage in families affected with Best`s macular dystrophy. Lod scores of 9.63, 9.12, 6.92, and 6.83 at zero recombination, were obtained with markers D11S1344, D11S1361, D11S1357 and D11S903, respectively. This data places the disease locus definitvely within the region between PYGM and D11S871. Linkage has been significantly excluded in this region in the German family (FamE), thereby providing evidence for genetic heterogeneity in this disease. The retinal specific gene, rod outer membrane protein 1 (ROM1), which maps to this region, has been screened for mutations in family BTMD1 by SSCPE analysis and by direct sequencing. Some of the promoter region, the three exons, and both introns have been sequenced; however, no mutations were found. It is likely that a gene other than ROM1 within this region may be responsible for causing the disease phenotype.

  2. ALPHA MIS: Reference manual

    Energy Technology Data Exchange (ETDEWEB)

    Lovin, J.K.; Haese, R.L.; Heatherly, R.D.; Hughes, S.E.; Ishee, J.S.; Pratt, S.M.; Smith, D.W.

    1992-02-01

    ALPHA is a powerful and versatile management information system (MIS) initiated and sponsored and by the Finance and Business Management Division of Oak Ridge National Laboratory, who maintain and develop it in concert with the Business Systems Division for its Information Center. A general-purpose MIS, ALPHA allows users to access System 1022 and System 1032 databases to obtain and manage information. From a personal computer or a data terminal, Energy Systems employees can use ALPHA to control their own report reprocessing. Using four general commands (Database, Select, Sort, and Report) they can (1) choose a mainframe database, (2) define subsets within it, (3) sequentially order a subset by one or more variables, and (4) generate a report with their own or a canned format.

  3. Ordered subset linkage analysis supports a susceptibility locus for age-related macular degeneration on chromosome 16p12

    Directory of Open Access Journals (Sweden)

    Weeks Daniel E

    2004-07-01

    Full Text Available Abstract Background Age-related macular degeneration (AMD is a complex disorder that is responsible for the majority of central vision loss in older adults living in developed countries. Phenotypic and genetic heterogeneity complicate the analysis of genome-wide scans for AMD susceptibility loci. The ordered subset analysis (OSA method is an approach for reducing heterogeneity, increasing statistical power for detecting linkage, and helping to define the most informative data set for follow-up analysis. OSA assesses the linkage evidence in subsets of potentially more homogeneous families by rank-ordering family-specific lod scores with respect to trait-associated covariates or phenotypic features. Here, we present results of incorporating five continuous covariates into our genome-wide linkage analysis of 389 microsatellite markers in 62 multiplex families: Body mass index (BMI, systolic (SBP and diastolic (DBP blood pressure, intraocular pressure (IOP, and pack-years of cigarette smoking. Chromosome-wide significance of increases in nonparametric multipoint lod scores in covariate-defined subsets relative to the overall sample was assessed by permutation. Results Using a correction for testing multiple covariates, statistically significant lod score increases were observed for two chromosomal regions: 14q13 with a lod score of 3.2 in 28 families with average IOP ≤ 15.5 (p = 0.002, and 6q14 with a lod score of 1.6 in eight families with average BMI ≥ 30.1 (p = 0.0004. On chromosome 16p12, nominally significant lod score increases (p ≤ 0.05, up to a lod score of 2.9 in 32 families, were observed with several covariate orderings. While less significant, this was the only region where linkage evidence was associated with multiple clinically meaningful covariates and the only nominally significant finding when analysis was restricted to advanced forms of AMD. Families with linkage to 16p12 had higher averages of SBP, IOP and BMI and were

  4. Linkage and Genetic Association in Severe Asthma.

    Science.gov (United States)

    Jones, Bridgette L; Rosenwasser, Lanny J

    2016-08-01

    A significant body of work in the genetics of asthma currently exists. However, current knowledge has not been clarifying in understanding the pathophysiology of asthma and therapeutic treatment of the disease. Severe asthma in adults and children is a significant burden in relation to disproportionate disease morbidity, mortality, and health utilization. This disease phenotype is not well understood; current effective treatment regimens are limited. Genetic studies may lead to improved understanding of the pathophysiology of severe asthma and identification of relevant subsets, which allow more targeted and effective therapies and the realization of Precision Medicine in asthma. PMID:27401617

  5. ANALYSIS OF INTER SECTORAL LINKAGES IN SEMARANG REGENCY

    Directory of Open Access Journals (Sweden)

    Fafurida

    2014-03-01

    Full Text Available This research aims to analyze inter economic sectoral linkages and to arrange the Klassen typology of economic sectors in Semarang Regency. The Klassen typology is composed from the result of the linkage analysis. To construct the analysis, this paper also utulizes the input-output analysis. It finds that service sector has the highest backward linkage while farming sector has the highest forward linkage. Based on the Klassen typology analysis, sectors with the highest backward and forward linkages and potential to be the leading sector are farming sector, dan trade, hotel and restaurant sector.Keywords: Backward linkage,forward linkage, Klassen typologyJEL classification number: R15, O21AbstrakPenelitian ini bertujuan untuk mengkaji seberapa besar keterkaitan antar sektor ekonomi di Kabupaten Semarang dan memetakan tipologi Klassennya. Tipologi Klasen disusun berdasarkan hasil perhitungan analisis keterkaitannya. Untuk menyusun analisis tersebut, paper ini juga menggunakan analisis input-output. Hasil penelitian menunjukkan bahwa sektor jasa memiliki keterkaitan ke belakang tertinggi dibandingkan dengan sektor lainnya. Sementara itu, sektor pertanian merupakan sektor yang memiliki keterkaitan ke depan tertinggi. Berdasarkan hasil analisis tipologi Klassen, sektor yang memiliki keterkaitan ke depan dan ke belakang yang tinggi dan dapat menjadi sektor unggulan adalah sektor perdagangan, hotel dan sektor restoran.Kata kunci: Keterkaitan ke belakang, keterkaitan ke depan, tipologi KlassenJEL classification numbers: R15, O21

  6. Metabolic phenotype of bladder cancer.

    Science.gov (United States)

    Massari, Francesco; Ciccarese, Chiara; Santoni, Matteo; Iacovelli, Roberto; Mazzucchelli, Roberta; Piva, Francesco; Scarpelli, Marina; Berardi, Rossana; Tortora, Giampaolo; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-04-01

    Metabolism of bladder cancer represents a key issue for cancer research. Several metabolic altered pathways are involved in bladder tumorigenesis, representing therefore interesting targets for therapy. Tumor cells, including urothelial cancer cells, rely on a peculiar shift to aerobic glycolysis-dependent metabolism (the Warburg-effect) as the main energy source to sustain their uncontrolled growth and proliferation. Therefore, the high glycolytic flux depends on the overexpression of glycolysis-related genes (SRC-3, glucose transporter type 1 [GLUT1], GLUT3, lactic dehydrogenase A [LDHA], LDHB, hexokinase 1 [HK1], HK2, pyruvate kinase type M [PKM], and hypoxia-inducible factor 1-alpha [HIF-1α]), resulting in an overproduction of pyruvate, alanine and lactate. Concurrently, bladder cancer metabolism displays an increased expression of genes favoring the pentose phosphate pathway (glucose-6-phosphate dehydrogenase [G6PD]) and the fatty-acid synthesis (fatty acid synthase [FASN]), along with a decrease of AMP-activated protein kinase (AMPK) and Krebs cycle activities. Moreover, the PTEN/PI3K/AKT/mTOR pathway, hyper-activated in bladder cancer, acts as central regulator of aerobic glycolysis, hence contributing to cancer metabolic switch and tumor cell proliferation. Besides glycolysis, glycogen metabolism pathway plays a robust role in bladder cancer development. In particular, the overexpression of GLUT-1, the loss of the tumor suppressor glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL), and the increased activity of the tumor promoter enzyme glycogen phosphorylase impair glycogen metabolism. An increase in glucose uptake, decrease in normal cellular glycogen storage, and overproduction of lactate are consequences of decreased oxidative phosphorylation and inability to reuse glucose into the pentose phosphate and de novo fatty acid synthesis pathways. Moreover, AGL loss determines augmented levels of the serine-to-glycine enzyme

  7. A linkage study of candidate loci in familial Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Westerberg Lisa

    2003-07-01

    Full Text Available Abstract Background Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Most cases are sporadic, however familial cases do exist. We examined 12 families with familial Parkinson's disease ascertained at the Movement Disorder clinic at the Oregon Health Sciences University for genetic linkage to a number of candidate loci. These loci have been implicated in familial Parkinson's disease or in syndromes with a clinical presentation that overlaps with parkinsonism, as well as potentially in the pathogenesis of the disease. Methods The examined loci were PARK3, Parkin, DRD (dopa-responsive dystonia, FET1 (familial essential tremor, BDNF (brain-derived neurotrophic factor, GDNF (glial cell line-derived neurotrophic factor, Ret, DAT1 (the dopamine transporter, Nurr1 and Synphilin-1. Linkage to the α-synuclein gene and the Frontotemporal dementia with parkinsonism locus on chromosome 17 had previously been excluded in the families included in this study. Using Fastlink, Genehunter and Simwalk both parametric and model-free non-parametric linkage analyses were performed. Results In the multipoint parametric linkage analysis lod scores were below -2 for all loci except FET1 and Synphilin-1 under an autosomal dominant model with incomplete penetrance. Using non-parametric linkage analysis there was no evidence for linkage, although linkage could not be excluded. A few families showed positive parametric and non-parametric lod scores indicating possible genetic heterogeneity between families, although these scores did not reach any degree of statistical significance. Conclusions We conclude that in these families there was no evidence for linkage to any of the loci tested, although we were unable to exclude linkage with both parametric and non-parametric methods.

  8. Multipoint linkage detection in the presence of heterogeneity.

    Science.gov (United States)

    Chiu, Yen-Feng; Liang, Kung-Yee; Beaty, Terri H

    2002-06-01

    Linkage heterogeneity is common for complex diseases. It is well known that loss of statistical power for detecting linkage will result if one assumes complete homogeneity in the presence of linkage heterogeneity. To this end, Smith (1963, Annals of Human Genetics 27, 175-182) proposed an admixture model to account for linkage heterogeneity. It is well known that for this model, the conventional chi-squared approximation to the likelihood ratio test for no linkage does not apply even when the sample size is large. By dealing with nuclear families and one marker at a time for genetic diseases with simple modes of inheritance, score-based test statistics (Liang and Rathouz, 1999, Biometrics 55, 65-74) and likelihood-ratio-based test statistics (Lemdani and Pons, 1995, Biometrics 51, 1033-1041) have been proposed which have a simple large-sample distribution under the null hypothesis of linkage. In this paper, we extend their work to more practical situations that include information from multiple markers and multi-generational pedigrees while allowing for a class of general genetic models. Three different approaches are proposed to eliminate the nuisance parameters in these test statistics. We show that all three approaches lead to the same asymptotic distribution under the null hypothesis of no linkage. Simulation results show that the proposed test statistics have adequate power to detect linkage and that the performances of these two classes of test statistics are quite comparable. We have applied the proposed method to a family study of asthma (Barnes et al., 1996), in which the score-based test shows evidence of linkage with p-value <0.0001 in the region of interest on chromosome 12. Additionally, we have implemented this score-based test within the frequently used computer package GENEHUNTER.

  9. Amphibian Sex Determination: Segregation and Linkage Analysis Using Members of the Tiger Salamander Species Complex (Ambystoma mexicanum and A. t. tigrinum)

    OpenAIRE

    Smith, Jeramiah J.; Voss, S. Randal

    2009-01-01

    Little is known about the genetic basis of sex determination in vertebrates though considerable progress has been made in recent years. In this study, segregation analysis and linkage mapping were performed to localize an amphibian sex-determining locus (ambysex) in the tiger salamander (Ambystoma) genome. Segregation of sex phenotypes (male, female) among 2nd generation individuals of interspecific crosses (A. mexicanum x A. t. tigrinum) was consistent with Mendelian expectations, although a...

  10. Linkage and association analyses identify a candidate region for apoB level on chromosome 4q32.3 in FCHL families.

    Science.gov (United States)

    Wijsman, Ellen M; Rothstein, Joseph H; Igo, Robert P; Brunzell, John D; Motulsky, Arno G; Jarvik, Gail P

    2010-06-01

    Familial combined hyperlipidemia (FCHL) is a complex trait leading to cardiovascular disease (CVD) risk. Elevated levels and size of apolipoprotein B (apoB) and low-density lipoprotein (LDL) are associated with FCHL, which is genetically heterogeneous and is likely caused by rare variants. We carried out a linkage-based genome scan of four large FCHL pedigrees for apoB level that is independent of LDL: apoB level that is adjusted for LDL level and size. Follow-up included SNP genotyping in the region with the strongest evidence of linkage. Several regions with the evidence of linkage in individual pedigrees support the rare variant model. Evidence of linkage was strongest on chromosome 4q, with multipoint analysis in one pedigree giving LOD = 3.1 with a parametric model, and a log Bayes Factor = 1.5 from a Bayesian oligogenic approach. Of the 293 SNPs spanning the implicated region on 4q, rs6829588 completely explained the evidence of linkage. This SNP accounted for 39% of the apoB phenotypic variance, with heterozygotes for this SNP having a trait value that was approximately 30% higher than that of the high-frequency homozygote, thus identifying and considerably refining a strong candidate region. These results illustrate the advantage of using large pedigrees in the search for rare variants: reduced genetic heterogeneity within single pedigrees coupled with the large number of individuals segregating otherwise-rare single variants leads to high power to implicate such variants.

  11. The $\\alpha_S$ Dependence of Parton Distributions

    OpenAIRE

    Martin, A. D.; Stirling, W. J.; Roberts, R G

    1995-01-01

    We perform next-to-leading order global analyses of deep inelastic and related data for different fixed values of $\\alpha_S (M_Z^2)$. We present sets of parton distributions for six values of $\\alpha_S$ in the range 0.105 to 0.130. We display the $(x, Q^2)$ domains with the largest parton uncertainty and we discuss how forthcoming data may be able to improve the determination of the parton densities.

  12. Structures of multi-branched dextrins produced by saccharifyiing alpha-amylase from starch.

    Science.gov (United States)

    Umeki, K; Yamamoto, T

    1975-11-01

    From the digest of beta-limit dextrin (prepared from glutinous rice starch) with saccharifying alpha-amylase of Bacillus subtilis [EC 3.2.1.1] (BSA), two extensibely branched dextrins consisting of nine (No. 6, Fig. 1) and ten (No 7, Fig.1) glucose units were isolated by paper chromatography. Structural analysis using various enzymes revealed that No. 6 and No. 7 were both mixtures of four triply branched dextrins. They had structures which were built up with 63-alpha-glucosylmaltotriose and/or 62-alpha-glucosylmaltose as a linking unit. However, the branching configuration and the minimum alpha-1, 4-glucosidic linkages existing between two branches followed one of the three structures shown below: (see article). PMID:814118

  13. Genomic variation in rice: genesis of highly polymorphic linkage blocks during domestication.

    Directory of Open Access Journals (Sweden)

    Tian Tang

    2006-11-01

    Full Text Available Genomic regions that are unusually divergent between closely related species or racial groups can be particularly informative about the process of speciation or the operation of natural selection. The two sequenced genomes of cultivated Asian rice, Oryza sativa, reveal that at least 6% of the genomes are unusually divergent. Sequencing of ten unlinked loci from the highly divergent regions consistently identified two highly divergent haplotypes with each locus in nearly complete linkage disequilibrium among 25 O. sativa cultivars and 35 lines from six wild species. The existence of two highly divergent haplotypes in high divergence regions in species from all geographical areas (Africa, Asia, and Oceania was in contrast to the low polymorphism and low linkage disequilibrium that were observed in other parts of the genome, represented by ten reference loci. While several natural processes are likely to contribute to this pattern of genomic variation, domestication may have greatly exaggerated the trend. In this hypothesis, divergent haplotypes that were adapted to different geographical and ecological environments migrated along with humans during the development of domesticated varieties. If true, these high divergence regions of the genome would be enriched for loci that contribute to the enormous range of phenotypic variation observed among domesticated breeds.

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

    Science.gov (United States)

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

    2007-01-01

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

  15. Genetic diversity and linkage disequilibrium analysis in elite sugar beet breeding lines and wild beet accessions.

    Science.gov (United States)

    Adetunji, Ibraheem; Willems, Glenda; Tschoep, Hendrik; Bürkholz, Alexandra; Barnes, Steve; Boer, Martin; Malosetti, Marcos; Horemans, Stefaan; van Eeuwijk, Fred

    2014-03-01

    Linkage disequilibrium decay in sugar beet is strongly affected by the breeding history, and varies extensively between and along chromosomes, allowing identification of known and unknown signatures of selection. Genetic diversity and linkage disequilibrium (LD) patterns were investigated in 233 elite sugar beet breeding lines and 91 wild beet accessions, using 454 single nucleotide polymorphisms (SNPs) and 418 SNPs, respectively. Principal coordinate analysis suggested the existence of three groups of germplasm, corresponding to the wild beets, the seed parent and the pollen parent breeding pool. LD was investigated in each of these groups, with and without correction for genetic relatedness. Without correction for genetic relatedness, in the pollen as well as the seed parent pool, LD persisted beyond 50 centiMorgan (cM) on four (2, 3, 4 and 5) and three chromosomes (2, 4 and 6), respectively; after correction for genetic relatedness, LD decayed after wild beet accessions, there was a strong LD decay: on average LD disappeared after 1 cM when LD was calculated with a correction for genetic relatedness. Persistence of LD was not only observed between distant SNPs on the same chromosome, but also between SNPs on different chromosomes. Regions on chromosomes 3 and 4 that harbor disease resistance and monogermy loci showed strong genetic differentiation between the pollen and seed parent pools. Other regions, on chromosomes 8 and 9, for which no a priori information was available with respect to their contribution to the phenotype, still contributed to clustering of lines in the elite breeding material.

  16. An integrative method for testing form-function linkages and reconstructed evolutionary pathways of masticatory specialization.

    Science.gov (United States)

    Tseng, Z Jack; Flynn, John J

    2015-06-01

    Morphology serves as a ubiquitous proxy in macroevolutionary studies to identify potential adaptive processes and patterns. Inferences of functional significance of phenotypes or their evolution are overwhelmingly based on data from living taxa. Yet, correspondence between form and function has been tested in only a few model species, and those linkages are highly complex. The lack of explicit methodologies to integrate form and function analyses within a deep-time and phylogenetic context weakens inferences of adaptive morphological evolution, by invoking but not testing form-function linkages. Here, we provide a novel approach to test mechanical properties at reconstructed ancestral nodes/taxa and the strength and direction of evolutionary pathways in feeding biomechanics, in a case study of carnivorous mammals. Using biomechanical profile comparisons that provide functional signals for the separation of feeding morphologies, we demonstrate, using experimental optimization criteria on estimation of strength and direction of functional changes on a phylogeny, that convergence in mechanical properties and degree of evolutionary optimization can be decoupled. This integrative approach is broadly applicable to other clades, by using quantitative data and model-based tests to evaluate interpretations of function from morphology and functional explanations for observed macroevolutionary pathways. PMID:25994295

  17. Genetics Home Reference: alpha thalassemia

    Science.gov (United States)

    ... for Disease Control and Prevention Centre for Genetics Education (Australia) Cooley's Anemia Foundation: Fact sheet about alpha thalassemia Disease InfoSearch: Alpha-Thalassemia Genomics Education Programme (UK) Information Center for Sickle Cell and ...

  18. Predicting sales performance: Strengthening the personality – job performance linkage

    NARCIS (Netherlands)

    T.B. Sitser (Thomas)

    2014-01-01

    markdownabstract__Abstract__ Many organizations worldwide use personality measures to select applicants for sales jobs or to assess incumbent sales employees. In the present dissertation, consisting of four independent studies, five approaches to strengthen the personality-sales performance linkage

  19. $\\alpha$-minimal Banach spaces

    CERN Document Server

    Rosendal, Christian

    2011-01-01

    A Banach space with a Schauder basis is said to be $\\alpha$-minimal for some countable ordinal $\\alpha$ if, for any two block subspaces, the Bourgain embeddability index of one into the other is at least $\\alpha$. We prove a dichotomy that characterises when a Banach space has an $\\alpha$-minimal subspace, which contributes to the ongoing project, initiated by W. T. Gowers, of classifying separable Banach spaces by identifying characteristic subspaces.

  20. Mapping multiple QTL using linkage disequilibrium and linkage analysis information and multitrait data

    Directory of Open Access Journals (Sweden)

    Goddard Mike E

    2004-05-01

    Full Text Available Abstract A multi-locus QTL mapping method is presented, which combines linkage and linkage disequilibrium (LD information and uses multitrait data. The method assumed a putative QTL at the midpoint of each marker bracket. Whether the putative QTL had an effect or not was sampled using Markov chain Monte Carlo (MCMC methods. The method was tested in dairy cattle data on chromosome 14 where the DGAT1 gene was known to be segregating. The DGAT1 gene was mapped to a region of 0.04 cM, and the effects of the gene were accurately estimated. The fitting of multiple QTL gave a much sharper indication of the QTL position than a single QTL model using multitrait data, probably because the multi-locus QTL mapping reduced the carry over effect of the large DGAT1 gene to adjacent putative QTL positions. This suggests that the method could detect secondary QTL that would, in single point analyses, remain hidden under the broad peak of the dominant QTL. However, no indications for a second QTL affecting dairy traits were found on chromosome 14.

  1. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M;

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection...

  2. The Broad Autism Phenotype Questionnaire

    Science.gov (United States)

    Hurley, Robert S. E.; Losh, Molly; Parlier, Morgan; Reznick, J. Steven; Piven, Joseph

    2007-01-01

    The broad autism phenotype (BAP) is a set of personality and language characteristics that reflect the phenotypic expression of the genetic liability to autism, in non-autistic relatives of autistic individuals. These characteristics are milder but qualitatively similar to the defining features of autism. A new instrument designed to measure the…

  3. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  4. Data Linkage: A powerful research tool with potential problems

    Directory of Open Access Journals (Sweden)

    Scott Ian

    2010-12-01

    Full Text Available Abstract Background Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes. Methods A narrative review, using structured search methods was undertaken. Key words "data linkage" and Mesh term "medical record linkage" were applied to Medline, EMBASE and CINAHL databases between 1991 and 2007. Abstract inclusion criteria were; the article attempted an empirical evaluation of methodological issues relating to data linkage and reported on patient characteristics, the study design included analysis of matched versus unmatched records, and the report was in English. Included articles were grouped thematically according to patient characteristics that were compared between matched and unmatched records. Results The search identified 1810 articles of which 33 (1.8% met inclusion criteria. There was marked heterogeneity in study methods and factors investigated. Characteristics that were unevenly distributed among matched and unmatched records were; age (72% of studies, sex (50% of studies, race (64% of studies, geographical/hospital site (93% of studies, socio-economic status (82% of studies and health status (72% of studies. Conclusion A number of relevant patient or population factors may be associated with incomplete data linkage resulting in systematic bias in reported clinical outcomes. Readers should consider these factors in interpreting the reported results of data linkage studies.

  5. Identifying Nanotechnological Linkages in the Finnish Economy - An Explorative Study

    OpenAIRE

    Nikulainen, Tuomo

    2007-01-01

    Nanotechnology, as an emerging science-based technology, is seen to have great potential both in scientific as well as economic terms. In this paper the focus is on identifying the technological linkages between the Finnish nanotechnology community and the industrial incumbents. These technological link-ages are first observed at a broader level in comparison with the technological strengths of the Finnish industries, and then in greater detail at the level of companies. In addition, the abso...

  6. Emerging molecular phenotypes of asthma.

    Science.gov (United States)

    Ray, Anuradha; Oriss, Timothy B; Wenzel, Sally E

    2015-01-15

    Although asthma has long been considered a heterogeneous disease, attempts to define subgroups of asthma have been limited. In recent years, both clinical and statistical approaches have been utilized to better merge clinical characteristics, biology, and genetics. These combined characteristics have been used to define phenotypes of asthma, the observable characteristics of a patient determined by the interaction of genes and environment. Identification of consistent clinical phenotypes has now been reported across studies. Now the addition of various 'omics and identification of specific molecular pathways have moved the concept of clinical phenotypes toward the concept of molecular phenotypes. The importance of these molecular phenotypes is being confirmed through the integration of molecularly targeted biological therapies. Thus the global term asthma is poised to become obsolete, being replaced by terms that more specifically identify the pathology associated with the disease. PMID:25326577

  7. Skewed RAPD markers in linkage maps of Citrus

    Directory of Open Access Journals (Sweden)

    Roberto Pedroso de Oliveira

    2004-01-01

    Full Text Available The objective of this work was to analyze the effects of RAPD markers with skewed segregation on genetic linkage maps. Segregation data for 123 Citrus sinensis (L. Osbeck cv. Pêra markers and 53 C. reticulata Blanco cv. Cravo markers in F1 progeny composed of 94 hybrids were used. Genetic linkage maps of the two varieties were constructed with non-skewed markers (p < 0.05 and p < 0.01 using the program MAPMAKER 3.0 and a pseudo-testcross strategy. The maps were compared to those constructed with all markers. Alterations in the genetic distances were observed based on the location of the skewed markers within the linkage groups. Generally, the skewed markers were located at the end of the linkage groups, sometimes forming entire linkage groups, without causing significant distance modifications. However, skewed markers located between non-skewed markers caused significant distance modifications and, in some cases, altered the order of the markers. Most of the skewed markers can be included in linkage maps, but in each case the degree of distance modification caused by each marker needs to be assessed.

  8. The assembly modes of rigid 11-bar linkages

    CERN Document Server

    Emiris, Ioannis Z

    2010-01-01

    Designing an m-bar linkage with a maximal number of assembly modes is important in robot kinematics, and has further applications in structural biology and computational geometry. A related question concerns the number of assembly modes of rigid mechanisms as a function of their nodes n, which is uniquely defined given m. Rigid 11-bar linkages, where n=7, are the simplest planar linkages for which these questions were still open. It will be proven that the maximal number of assembly modes of such linkages is exactly 56. The rigidity of a linkage is captured by a polynomial system derived from distance, or Cayley-Menger, matrices. The upper bound on the number of assembly modes is obtained as the mixed volume of a 5x5 system. An 11-bar linkage admitting 56 configurations is constructed using stochastic optimisation methods. This yields a general lower bound of $\\Omega(2.3^n)$ on the number of assembly modes, slightly improving the current record of $\\Omega(2.289^n)$, while the best known upper bound is roughly...

  9. Genome-wide linkage analysis for human longevity

    DEFF Research Database (Denmark)

    Beekman, Marian; Blanché, Hélène; Perola, Markus;

    2013-01-01

    Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian...... sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.......02 and P-value = 1.0 × 10(-5) , respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results...

  10. Identification of quantitative trait loci underlying milk traits in Spanish dairy sheep using linkage plus combined linkage disequilibrium and linkage analysis approaches.

    Science.gov (United States)

    Garcia-Gámez, E; Gutiérrez-Gil, B; Suarez-Vega, A; de la Fuente, L F; Arranz, J J

    2013-09-01

    In this study, 2 procedures were used to analyze a data set from a whole-genome scan, one based on linkage analysis information and the other combing linkage disequilibrium and linkage analysis (LDLA), to determine the quantitative trait loci (QTL) influencing milk production traits in sheep. A total of 1,696 animals from 16 half-sib families were genotyped using the OvineSNP50 BeadChip (Illumina Inc., San Diego, CA) and analysis was performed using a daughter design. Moreover, the same data set has been previously investigated through a genome-wide association (GWA) analysis and a comparison of results from the 3 methods has been possible. The linkage analysis and LDLA methodologies yielded different results, although some significantly associated regions were common to both procedures. The linkage analysis detected 3 overlapping genome-wise significant QTL on sheep chromosome (OAR) 2 influencing milk yield, protein yield, and fat yield, whereas 34 genome-wise significant QTL regions were detected using the LDLA approach. The most significant QTL for protein and fat percentages was detected on OAR3, which was reported in a previous GWA analysis. Both the linkage analysis and LDLA identified many other chromosome-wise significant associations across different sheep autosomes. Additional analyses were performed on OAR2 and OAR3 to determine the possible causality of the most significant polymorphisms identified for these genetic effects by the previously reported GWA analysis. For OAR3, the analyses demonstrated additional genetic proof of the causality previously suggested by our group for a single nucleotide polymorphism located in the α-lactalbumin gene (LALBA). In summary, although the results shown here suggest that in commercial dairy populations, the LDLA method exhibits a higher efficiency to map QTL than the simple linkage analysis or linkage disequilibrium methods, we believe that comparing the 3 analysis methods is the best approach to obtain a global

  11. Resting alpha activity predicts learning ability in alpha neurofeedback

    Directory of Open Access Journals (Sweden)

    Wenya eNan

    2014-07-01

    Full Text Available Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the training parameter changes between two periods, within a short period and across the whole training time. It was found that the resting alpha amplitude measured before training had significant positive correlations with all learning indices and could be used as a predictor for the learning ability prediction. This finding would help the researchers in not only predicting the training efficacy in individuals but also gaining further insight into the mechanisms of alpha neurofeedback.

  12. Pyruvate dehydrogenase complex activity controls metabolic and malignant phenotype in cancer cells.

    Science.gov (United States)

    McFate, Thomas; Mohyeldin, Ahmed; Lu, Huasheng; Thakar, Jay; Henriques, Jeremy; Halim, Nader D; Wu, Hong; Schell, Michael J; Tsang, Tsz Mon; Teahan, Orla; Zhou, Shaoyu; Califano, Joseph A; Jeoung, Nam Ho; Harris, Robert A; Verma, Ajay

    2008-08-15

    High lactate generation and low glucose oxidation, despite normal oxygen conditions, are commonly seen in cancer cells and tumors. Historically known as the Warburg effect, this altered metabolic phenotype has long been correlated with malignant progression and poor clinical outcome. However, the mechanistic relationship between altered glucose metabolism and malignancy remains poorly understood. Here we show that inhibition of pyruvate dehydrogenase complex (PDC) activity contributes to the Warburg metabolic and malignant phenotype in human head and neck squamous cell carcinoma. PDC inhibition occurs via enhanced expression of pyruvate dehydrogenase kinase-1 (PDK-1), which results in inhibitory phosphorylation of the pyruvate dehydrogenase alpha (PDHalpha) subunit. We also demonstrate that PDC inhibition in cancer cells is associated with normoxic stabilization of the malignancy-promoting transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) by glycolytic metabolites. Knockdown of PDK-1 via short hairpin RNA lowers PDHalpha phosphorylation, restores PDC activity, reverts the Warburg metabolic phenotype, decreases normoxic HIF-1alpha expression, lowers hypoxic cell survival, decreases invasiveness, and inhibits tumor growth. PDK-1 is an HIF-1-regulated gene, and these data suggest that the buildup of glycolytic metabolites, resulting from high PDK-1 expression, may in turn promote HIF-1 activation, thus sustaining a feed-forward loop for malignant progression. In addition to providing anabolic support for cancer cells, altered fuel metabolism thus supports a malignant phenotype. Correction of metabolic abnormalities offers unique opportunities for cancer treatment and may potentially synergize with other cancer therapies. PMID:18541534

  13. Genetic Linkage Map Construction and QTL Analysis of Two Interspecific Reproductive Isolation Traits in Sponge Gourd.

    Science.gov (United States)

    Wu, Haibin; He, Xiaoli; Gong, Hao; Luo, Shaobo; Li, Mingzhu; Chen, Junqiu; Zhang, Changyuan; Yu, Ting; Huang, Wangping; Luo, Jianning

    2016-01-01

    The hybrids between Luffa acutangula (L.) Roxb. and L.cylindrica (L.) Roem. have strong heterosis effects. However, some reproductive isolation traits hindered their normal hybridization and fructification, which was mainly caused by the flowering time and hybrid pollen sterility. In order to study the genetic basis of two interspecific reproductive isolation traits, we constructed a genetic linkage map using an F2 population derived from a cross between S1174 [L. acutangula (L.) Roxb.] and 93075 [L. cylindrica (L.) Roem.]. The map spans 1436.12 CentiMorgans (cM), with an average of 8.11 cM among markers, and consists of 177 EST-SSR markers distributed in 14 linkage groups (LG) with an average of 102.58 cM per LG. Meanwhile, we conducted colinearity analysis between the sequences of EST-SSR markers and the genomic sequences of cucumber, melon and watermelon. On the basis of genetic linkage map, we conducted QTL mapping of two reproductive isolation traits in sponge gourd, which were the flowering time and hybrid male sterility. Two putative QTLs associated with flowering time (FT) were both detected on LG 1. The accumulated contribution of these two QTLs explained 38.07% of the total phenotypic variance (PV), and each QTL explained 15.36 and 22.71% of the PV respectively. Four QTLs for pollen fertility (PF) were identified on LG 1 (qPF1.1 and qPF1.2), LG 3 (qPF3) and LG 7 (qPF7), respectively. The percentage of PF explained by these QTLs varied from 2.91 to 16.79%, and all together the four QTLs accounted for 39.98% of the total PV. Our newly developed EST-SSR markers and linkage map are very useful for gene mapping, comparative genomics and molecular marker-assisted breeding. These QTLs for interspecific reproductive isolation will also contribute to the cloning of genes relating to interspecific reproductive isolation and the utilization of interspecific heterosis in sponge gourd in further studies. PMID:27458467

  14. Genetic Linkage Map Construction and QTL Analysis of Two Interspecific Reproductive Isolation Traits in Sponge Gourd

    Science.gov (United States)

    Wu, Haibin; He, Xiaoli; Gong, Hao; Luo, Shaobo; Li, Mingzhu; Chen, Junqiu; Zhang, Changyuan; Yu, Ting; Huang, Wangping; Luo, Jianning

    2016-01-01

    The hybrids between Luffa acutangula (L.) Roxb. and L.cylindrica (L.) Roem. have strong heterosis effects. However, some reproductive isolation traits hindered their normal hybridization and fructification, which was mainly caused by the flowering time and hybrid pollen sterility. In order to study the genetic basis of two interspecific reproductive isolation traits, we constructed a genetic linkage map using an F2 population derived from a cross between S1174 [L. acutangula (L.) Roxb.] and 93075 [L. cylindrica (L.) Roem.]. The map spans 1436.12 CentiMorgans (cM), with an average of 8.11 cM among markers, and consists of 177 EST-SSR markers distributed in 14 linkage groups (LG) with an average of 102.58 cM per LG. Meanwhile, we conducted colinearity analysis between the sequences of EST-SSR markers and the genomic sequences of cucumber, melon and watermelon. On the basis of genetic linkage map, we conducted QTL mapping of two reproductive isolation traits in sponge gourd, which were the flowering time and hybrid male sterility. Two putative QTLs associated with flowering time (FT) were both detected on LG 1. The accumulated contribution of these two QTLs explained 38.07% of the total phenotypic variance (PV), and each QTL explained 15.36 and 22.71% of the PV respectively. Four QTLs for pollen fertility (PF) were identified on LG 1 (qPF1.1 and qPF1.2), LG 3 (qPF3) and LG 7 (qPF7), respectively. The percentage of PF explained by these QTLs varied from 2.91 to 16.79%, and all together the four QTLs accounted for 39.98% of the total PV. Our newly developed EST-SSR markers and linkage map are very useful for gene mapping, comparative genomics and molecular marker-assisted breeding. These QTLs for interspecific reproductive isolation will also contribute to the cloning of genes relating to interspecific reproductive isolation and the utilization of interspecific heterosis in sponge gourd in further studies. PMID:27458467

  15. Combining Alphas via Bounded Regression

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze

    2015-11-01

    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  16. Orthopositronium lifetime. Analytic results in O ({alpha}) and O ({alpha}{sup 3} ln {alpha})

    Energy Technology Data Exchange (ETDEWEB)

    Kniehl, B.A.; Kotikov, A.V.; Veretin, O.L. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

    2008-06-15

    We present the O({alpha}) and O({alpha}{sup 3}ln {alpha}) corrections to the total decay width of orthopositronium in closed analytic form, in terms of basic transcendental numbers, which can be evaluated numerically to arbitrary precision. (orig.)

  17. Whole exome sequencing combined with linkage analysis identifies a novel 3 bp deletion in NR5A1.

    Science.gov (United States)

    Eggers, Stefanie; Smith, Katherine R; Bahlo, Melanie; Looijenga, Leendert H J; Drop, Stenvert L S; Juniarto, Zulfa A; Harley, Vincent R; Koopman, Peter; Faradz, Sultana M H; Sinclair, Andrew H

    2015-04-01

    Disorders of sex development (DSDs) encompass a broad spectrum of conditions affecting the development of the gonads and genitalia. The underlying causes for DSDs include gain or loss of function variants in genes responsible for gonad development or steroidogenesis. Most patients with DSD have an unknown genetic etiology and cannot be given an accurate diagnosis. We used whole exome capture and massively parallel sequencing to analyse a large family with 46,XY DSD and 46,XX premature ovarian insufficiency. In addition, we used a recently developed method for linkage analysis using genotypes extracted from the MPS data. This approach identified a unique linkage peak on chromosome 9 and a novel, 3 bp, in-frame deletion in exon six of NR5A1 (steroidogenic factor-1 or SF1) in all affected individuals. We confirmed that the variant disrupts the SF1 protein and its ability to bind and regulate downstream genes. NR5A1 has key roles at multiple points in gonad development and steroidogenic pathways. The variant described here affects the function of SF1 in early testis development and later ovarian function, ultimately leading to the 46,XY DSD and 46,XX premature ovarian insufficiency phenotypes, respectively. This study shows that even at low coverage, whole exome sequencing, when combined with linkage analysis, can be a powerful tool to identify rapidly the disease-causing variant in large pedigrees.

  18. Identification of QTLs associated with callogenesis and embryogenesis in oil palm using genetic linkage maps improved with SSR markers.

    Directory of Open Access Journals (Sweden)

    Ngoot-Chin Ting

    Full Text Available Clonal reproduction of oil palm by means of tissue culture is a very inefficient process. Tissue culturability is known to be genotype dependent with some genotypes being more amenable to tissue culture than others. In this study, genetic linkage maps enriched with simple sequence repeat (SSR markers were developed for dura (ENL48 and pisifera (ML161, the two fruit forms of oil palm, Elaeis guineensis. The SSR markers were mapped onto earlier reported parental maps based on amplified fragment length polymorphism (AFLP and restriction fragment length polymorphism (RFLP markers. The new linkage map of ENL48 contains 148 markers (33 AFLPs, 38 RFLPs and 77 SSRs in 23 linkage groups (LGs, covering a total map length of 798.0 cM. The ML161 map contains 240 markers (50 AFLPs, 71 RFLPs and 119 SSRs in 24 LGs covering a total of 1,328.1 cM. Using the improved maps, two quantitative trait loci (QTLs associated with tissue culturability were identified each for callusing rate and embryogenesis rate. A QTL for callogenesis was identified in LGD4b of ENL48 and explained 17.5% of the phenotypic variation. For embryogenesis rate, a QTL was detected on LGP16b in ML161 and explained 20.1% of the variation. This study is the first attempt to identify QTL associated with tissue culture amenity in oil palm which is an important step towards understanding the molecular processes underlying clonal regeneration of oil palm.

  19. Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Kyllo, J.H.; Collins, M.M.; Vetter, K.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others

    1996-03-29

    Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene of chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes. 25 refs., 5 figs., 2 tabs.

  20. Alpha-synuclein suppression by targeted small interfering RNA in the primate substantia nigra.

    Directory of Open Access Journals (Sweden)

    Alison L McCormack

    Full Text Available The protein alpha-synuclein is involved in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Its toxic potential appears to be enhanced by increased protein expression, providing a compelling rationale for therapeutic strategies aimed at reducing neuronal alpha-synuclein burden. Here, feasibility and safety of alpha-synuclein suppression were evaluated by treating monkeys with small interfering RNA (siRNA directed against alpha-synuclein. The siRNA molecule was chemically modified to prevent degradation by exo- and endonucleases and directly infused into the left substantia nigra. Results compared levels of alpha-synuclein mRNA and protein in the infused (left vs. untreated (right hemisphere and revealed a significant 40-50% suppression of alpha-synuclein expression. These findings could not be attributable to non-specific effects of siRNA infusion since treatment of a separate set of animals with luciferase-targeting siRNA produced no changes in alpha-synuclein. Infusion with alpha-synuclein siRNA, while lowering alpha-synuclein expression, had no overt adverse consequences. In particular, it did not cause tissue inflammation and did not change (i the number and phenotype of nigral dopaminergic neurons, and (ii the concentrations of striatal dopamine and its metabolites. The data represent the first evidence of successful anti-alpha-synuclein intervention in the primate substantia nigra and support further development of RNA interference-based therapeutics.

  1. RLT-S: A Web System for Record Linkage.

    Directory of Open Access Journals (Sweden)

    Abdullah-Al Mamun

    Full Text Available Record linkage integrates records across multiple related data sources identifying duplicates and accounting for possible errors. Real life applications require efficient algorithms to merge these voluminous data sources to find out all records belonging to same individuals. Our recently devised highly efficient record linkage algorithms provide best-known solutions to this challenging problem.We have developed RLT-S, a freely available web tool, which implements our single linkage clustering algorithm for record linkage. This tool requires input data sets and a small set of configuration settings about these files to work efficiently. RLT-S employs exact match clustering, blocking on a specified attribute and single linkage based hierarchical clustering among these blocks.RLT-S is an implementation package of our sequential record linkage algorithm. It outperforms previous best-known implementations by a large margin. The tool is at least two times faster for any dataset than the previous best-known tools.RLT-S tool implements our record linkage algorithm that outperforms previous best-known algorithms in this area. This website also contains necessary information such as instructions, submission history, feedback, publications and some other sections to facilitate the usage of the tool.RLT-S is integrated into http://www.rlatools.com, which is currently serving this tool only. The tool is freely available and can be used without login. All data files used in this paper have been stored in https://github.com/abdullah009/DataRLATools. For copies of the relevant programs please see https://github.com/abdullah009/RLATools.

  2. Absence of linkage of apparently single gene mediated ADHD with the human syntenic region of the mouse mutant coloboma

    Energy Technology Data Exchange (ETDEWEB)

    Hess, E.J.; Rogan, P.K.; Domoto, M. [Pennsylvania State Univ. College of Medicine, Hershey, PA (United States)] [and others

    1995-12-18

    Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11-p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the traits studied suggested that the best fitting model was a sex-influenced, single gene, Mendelian pattern. Several genetic models were evaluated based on estimates of penetrance, phenocopy rate, and allele frequency derived from our patient population and those of other investigators. No significant linkage was detected between the disease locus and markers spanning this chromosome 20 interval. 39 refs., 2 figs., 1 tab.

  3. Low linkage disequilibrium in wild Anopheles gambiae s.l. populations

    Directory of Open Access Journals (Sweden)

    Harris Caroline

    2010-09-01

    Full Text Available Abstract Background In the malaria vector Anopheles gambiae, understanding diversity in natural populations and genetic components of important phenotypes such as resistance to malaria infection is crucial for developing new malaria transmission blocking strategies. The design and interpretation of many studies here depends critically on Linkage disequilibrium (LD. For example in association studies, LD determines the density of Single Nucleotide Polymorphisms (SNPs to be genotyped to represent the majority of the genomic information. Here, we aim to determine LD in wild An. gambiae s.l. populations in 4 genes potentially involved in mosquito immune responses against pathogens (Gambicin, NOS, REL2 and FBN9 using previously published and newly generated sequences. Results The level of LD between SNP pairs in cloned sequences of each gene was determined for 7 species (or incipient species of the An. gambiae complex. In all tested genes and species, LD between SNPs was low: even at short distances (2 2 ranged from 0.073 to 0.766. In most genes and species LD decayed very rapidly with increasing inter-marker distance. Conclusions These results are of great interest for the development of large scale polymorphism studies, as LD generally falls below any useful limit. It indicates that very fine scale SNP detection will be required to give an overall view of genome-wide polymorphism. Perhaps a more feasible approach to genome wide association studies is to use targeted approaches using candidate gene selection to detect association to phenotypes of interest.

  4. Rac inhibition reverses the phenotype of fibrotic fibroblasts.

    Directory of Open Access Journals (Sweden)

    Shi-wen Xu

    Full Text Available BACKGROUND: Fibrosis, the excessive deposition of scar tissue by fibroblasts, is one of the largest groups of diseases for which there is no therapy. Fibroblasts from lesional areas of scleroderma patients possess elevated abilities to contract matrix and produce alpha-smooth muscle actin (alpha-SMA, type I collagen and CCN2 (connective tissue growth factor, CTGF. The basis for this phenomenon is poorly understood, and is a necessary prerequisite for developing novel, rational anti-fibrotic strategies. METHODS AND FINDINGS: Compared to healthy skin fibroblasts, dermal fibroblasts cultured from lesional areas of scleroderma (SSc patients possess elevated Rac activity. NSC23766, a Rac inhibitor, suppressed the persistent fibrotic phenotype of lesional SSc fibroblasts. NSC23766 caused a decrease in migration on and contraction of matrix, and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. SSc fibroblasts possessed elevated Akt phosphorylation, which was also blocked by NSC23766. Overexpression of rac1 in normal fibroblasts induced matrix contraction and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. Rac1 activity was blocked by PI3kinase/Akt inhibition. Basal fibroblast activity was not affected by NSC23766. CONCLUSION: Rac inhibition may be considered as a novel treatment for the fibrosis observed in SSc.

  5. Dissecting the correlation structure of a bivariate phenotype: common genes or shared environment?

    Indian Academy of Sciences (India)

    Saurabh Ghosh

    2005-08-01

    High correlations between two quantitative traits may be either due to common genetic factors or common environmental factors or a combination of both. In this study, we develop statistical methods to extract the genetic contribution to the total correlation between the components of a bivariate phenotype. Using data on bivariate phenotypes and marker genotypes for sib-pairs, we propose a test for linkage between a common QTL and a marker locus based on the conditional cross-sib trait correlations (trait 1 of sib 1 – trait 2 of sib 2 and conversely) given the identity-by-descent (i.b.d.) sharing at the marker locus. We use Monte-Carlo simulations to evaluate the performance of the proposed test under different trait parameters and quantitative trait distributions. An application of the method is illustrated using data on two alcohol-related phenotypes from a project on the collaborative study on the genetics of alcoholism.

  6. A gene-rich linkage map in the dioecious species Actinidia chinensis (kiwifruit reveals putative X/Y sex-determining chromosomes

    Directory of Open Access Journals (Sweden)

    Gill Geoffrey P

    2009-03-01

    Full Text Available Abstract Background The genus Actinidia (kiwifruit consists of woody, scrambling vines, native to China, and only recently propagated as a commercial crop. All species described are dioecious, but the genetic mechanism for sex-determination is unknown, as is the genetic basis for many of the cluster of characteristics making up the unique fruit. It is, however, an important crop in the New Zealand economy, and a classical breeding program would benefit greatly by knowledge of the trait alleles carried by both female and male parents. The application of marker assisted selection (MAS in seedling populations would also aid the accurate and efficient development of novel fruit types for the market. Results Gene-rich female, male and consensus linkage maps of the diploid species A. chinensis have been constructed with 644 microsatellite markers. The maps consist of twenty-nine linkage groups corresponding to the haploid number n = 29. We found that sex-linked sequence characterized amplified region (SCAR markers and the 'Flower-sex' phenotype consistently mapped to a single linkage group, in a subtelomeric region, in a section of inconsistent marker order. The region also contained markers of expressed genes, some of unknown function. Recombination, assessed by allelic distribution and marker order stability, was, in the remainder of the linkage group, in accordance with other linkage groups. Fully informative markers to other genes in this linkage group identified the comparative linkage group in the female map, where recombination ratios determining marker order were similar to the autosomes. Conclusion We have created genetic linkage maps that define the 29 linkage groups of the haploid genome, and have revealed the position and extent of the sex-determining locus in A. chinensis. As all Actinidia species are dioecious, we suggest that the sex-determining loci of other Actinidia species will be similar to that region defined in our maps. As the

  7. Novel genetic linkage of rat Sp6 mutation to Amelogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Muto Taro

    2012-06-01

    Full Text Available Abstract Background Amelogenesis imperfecta (AI is an inherited disorder characterized by abnormal formation of tooth enamel. Although several genes responsible for AI have been reported, not all causative genes for human AI have been identified to date. AMI rat has been reported as an autosomal recessive mutant with hypoplastic AI isolated from a colony of stroke-prone spontaneously hypertensive rat strain, but the causative gene has not yet been clarified. Through a genetic screen, we identified the causative gene of autosomal recessive AI in AMI and analyzed its role in amelogenesis. Methods cDNA sequencing of possible AI-candidate genes so far identified using total RNA of day 6 AMI rat molars identified a novel responsible mutation in specificity protein 6 (Sp6. Genetic linkage analysis was performed between Sp6 and AI phenotype in AMI. To understand a role of SP6 in AI, we generated the transgenic rats harboring Sp6 transgene in AMI (Ami/Ami + Tg. Histological analyses were performed using the thin sections of control rats, AMI, and Ami/Ami + Tg incisors in maxillae, respectively. Results We found the novel genetic linkage between a 2-bp insertional mutation of Sp6 gene and the AI phenotype in AMI rats. The position of mutation was located in the coding region of Sp6, which caused frameshift mutation and disruption of the third zinc finger domain of SP6 with 11 cryptic amino acid residues and a stop codon. Transfection studies showed that the mutant protein can be translated and localized in the nucleus in the same manner as the wild-type SP6 protein. When we introduced the CMV promoter-driven wild-type Sp6 transgene into AMI rats, the SP6 protein was ectopically expressed in the maturation stage of ameloblasts associated with the extended maturation stage and the shortened reduced stage without any other phenotypical changes. Conclusion We propose the addition of Sp6 mutation as a new molecular diagnostic criterion for the

  8. Next-generation phenotypic screening.

    Science.gov (United States)

    Warchal, Scott J; Unciti-Broceta, Asier; Carragher, Neil O

    2016-07-01

    Phenotypic drug discovery (PDD) strategies are defined by screening and selection of hit or lead compounds based on quantifiable phenotypic endpoints without prior knowledge of the drug target. We outline the challenges associated with traditional phenotypic screening strategies and propose solutions and new opportunities to be gained by adopting modern PDD technologies. We highlight both historical and recent examples of approved drugs and new drug candidates discovered by modern phenotypic screening. Finally, we offer a prospective view of a new era of PDD underpinned by a wealth of technology advances in the areas of in vitro model development, high-content imaging and image informatics, mechanism-of-action profiling and target deconvolution. PMID:27357617

  9. Epigenetics in heart failure phenotypes.

    Science.gov (United States)

    Berezin, Alexander

    2016-12-01

    Chronic heart failure (HF) is a leading clinical and public problem posing a higher risk of morbidity and mortality in different populations. HF appears to be in both phenotypic forms: HF with reduced left ventricular ejection fraction (HFrEF) and HF with preserved left ventricular ejection fraction (HFpEF). Although both HF phenotypes can be distinguished through clinical features, co-morbidity status, prediction score, and treatment, the clinical outcomes in patients with HFrEF and HFpEF are similar. In this context, investigation of various molecular and cellular mechanisms leading to the development and progression of both HF phenotypes is very important. There is emerging evidence that epigenetic regulation may have a clue in the pathogenesis of HF. This review represents current available evidence regarding the implication of epigenetic modifications in the development of different HF phenotypes and perspectives of epigenetic-based therapies of HF. PMID:27335803

  10. Capturing phenotypes for precision medicine.

    Science.gov (United States)

    Robinson, Peter N; Mungall, Christopher J; Haendel, Melissa

    2015-10-01

    Deep phenotyping followed by integrated computational analysis of genotype and phenotype is becoming ever more important for many areas of genomic diagnostics and translational research. The overwhelming majority of clinical descriptions in the medical literature are available only as natural language text, meaning that searching, analysis, and integration of medically relevant information in databases such as PubMed is challenging. The new journal Cold Spring Harbor Molecular Case Studies will require authors to select Human Phenotype Ontology terms for research papers that will be displayed alongside the manuscript, thereby providing a foundation for ontology-based indexing and searching of articles that contain descriptions of phenotypic abnormalities-an important step toward improving the ability of researchers and clinicians to get biomedical information that is critical for clinical care or translational research. PMID:27148566

  11. Finding our way through phenotypes.

    Directory of Open Access Journals (Sweden)

    Andrew R Deans

    2015-01-01

    Full Text Available Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  12. Unfolding domains of recombinant fusion alpha alpha-tropomyosin.

    OpenAIRE

    Ishii, Y; Hitchcock-DeGregori, S.; Mabuchi, K; Lehrer, S S

    1992-01-01

    The thermal unfolding of the coiled-coil alpha-helix of recombinant alpha alpha-tropomyosin from rat striated muscle containing an additional 80-residue peptide of influenza virus NS1 protein at the N-terminus (fusion-tropomyosin) was studied with circular dichroism and fluorescence techniques. Fusion-tropomyosin unfolded in four cooperative transitions: (1) a pretransition starting at 35 degrees C involving the middle of the molecule; (2) a major transition at 46 degrees C involving no more ...

  13. The first genetic linkage map of Eucommia ulmoides

    Indian Academy of Sciences (India)

    Dawei Wang; Yu Li; Long Li; Yongcheng Wei; Zhouqi Li

    2014-04-01

    In accordance with pseudo-testcross strategy, the first genetic linkage map of Eucommia ulmoides Oliv. was constructed by an F1 population of 122 plants using amplified fragment length polymorphism (AFLP) markers. A total of 22 AFLP primer combinations generated 363 polymorphic markers. We selected 289 markers segregating as 1:1 and used them for constructing the parent-specific linkage maps. Among the candidate markers, 127 markers were placed on the maternal map LF and 108 markers on the paternal map Q1. The maternal map LF spanned 1116.1 cM in 14 linkage groups with a mean map distance of 8.78 cM; the paternal map Q1 spanned 929.6 cM in 12 linkage groups with an average spacing of 8.61 cM. The estimated coverage of the genome through two methods was 78.5 and 73.9% for LF, and 76.8 and 71.2% for Q1, respectively. This map is the first linkage map of E. ulmoides and provides a basis for mapping quantitative-trait loci and breeding applications.

  14. Alpha-mannosidosis

    Directory of Open Access Journals (Sweden)

    Nilssen Øivind

    2008-07-01

    Full Text Available Abstract Alpha-mannosidosis is an inherited lysosomal storage disorder characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual disability. It occurs in approximately 1 of 500,000 live births. The children are often born apparently normal, and their condition worsens progressively. Some children are born with ankle equinus or develop hydrocephalus in the first year of life. Main features are immune deficiency (manifested by recurrent infections, especially in the first decade of life, skeletal abnormalities (mild-to-moderate dysostosis multiplex, scoliosis and deformation of the sternum, hearing impairment (moderate-to-severe sensorineural hearing loss, gradual impairment of mental functions and speech, and often, periods of psychosis. Associated motor function disturbances include muscular weakness, joint abnormalities and ataxia. The facial trait include large head with prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, and prognathism. Slight strabismus is common. The clinical variability is significant, representing a continuum in severity. The disorder is caused by lysosomal alpha-mannosidase deficiency. Alpha-mannosidosis is inherited in an autosomal recessive fashion and is caused by mutations in the MAN2B1 gene located on chromosome 19 (19 p13.2-q12. Diagnosis is made by measuring acid alpha-mannosidase activity in leukocytes or other nucleated cells and can be confirmed by genetic testing. Elevated urinary secretion of mannose-rich oligosaccharides is suggestive, but not diagnostic. Differential diagnoses are mainly the other lysosomal storage diseases like the mucopolysaccharidoses. Genetic counseling should be given to explain the nature of the disease and to detect carriers. Antenatal diagnosis is possible, based on both biochemical and genetic methods. The management should be pro-active, preventing complications and treating

  15. High-density genetic linkage mapping in turbot (Scophthalmus maximus L. based on SNP markers and major sex- and growth-related regions detection.

    Directory of Open Access Journals (Sweden)

    Weiji Wang

    Full Text Available This paper describes the development of a high density consensus genetic linkage map of a turbot (Scophthalmus maximus L. family composed of 149 mapping individuals using Single Nucleotide Polymorphisms (SNP developed using the restriction-site associated DNA (RAD sequencing technique with the restriction enzyme, PstI. A total of 6,647 SNPs were assigned to 22 linkage groups, which is equal to the number of chromosome pairs in turbot. For the first time, the average marker interval reached 0.3958 cM, which is equal to approximately 0.1203 Mb of the turbot genome. The observed 99.34% genome coverage indicates that the linkage map was genome-wide. A total of 220 Quantitative Traits Locus (QTLs associated with two body length traits, two body weight traits in different growth periods and sex determination were detected with an LOD > 5.0 in 12 linkage groups (LGs, which explained the corresponding phenotypic variance (R2, ranging from 14.4-100%. Among them, 175 overlapped with linked SNPs, and the remaining 45 were located in regions between contiguous SNPs. According to the QTLs related to growth trait distribution and the changing of LGs during different growth periods, the growth traits are likely controlled by multi-SNPs distributed on several LGs; the effect of these SNPs changed during different growth periods. Most sex-related QTLs were detected at LG 21 with a linkage span of 70.882 cM. Additionally, a small number of QTLs with high feasibility and a narrow R2 distribution were also observed on LG7 and LG14, suggesting that multi LGs or chromosomes might be involved in sex determination. High homology was recorded between LG21 in Cynoglossus semilaevis and turbot. This high-saturated turbot RAD-Seq linkage map is undoubtedly a promising platform for marker assisted selection (MAS and flatfish genomics research.

  16. High-density genetic linkage mapping in turbot (Scophthalmus maximus L.) based on SNP markers and major sex- and growth-related regions detection.

    Science.gov (United States)

    Wang, Weiji; Hu, Yulong; Ma, Yu; Xu, Liyong; Guan, Jiantao; Kong, Jie

    2015-01-01

    This paper describes the development of a high density consensus genetic linkage map of a turbot (Scophthalmus maximus L.) family composed of 149 mapping individuals using Single Nucleotide Polymorphisms (SNP) developed using the restriction-site associated DNA (RAD) sequencing technique with the restriction enzyme, PstI. A total of 6,647 SNPs were assigned to 22 linkage groups, which is equal to the number of chromosome pairs in turbot. For the first time, the average marker interval reached 0.3958 cM, which is equal to approximately 0.1203 Mb of the turbot genome. The observed 99.34% genome coverage indicates that the linkage map was genome-wide. A total of 220 Quantitative Traits Locus (QTLs) associated with two body length traits, two body weight traits in different growth periods and sex determination were detected with an LOD > 5.0 in 12 linkage groups (LGs), which explained the corresponding phenotypic variance (R2), ranging from 14.4-100%. Among them, 175 overlapped with linked SNPs, and the remaining 45 were located in regions between contiguous SNPs. According to the QTLs related to growth trait distribution and the changing of LGs during different growth periods, the growth traits are likely controlled by multi-SNPs distributed on several LGs; the effect of these SNPs changed during different growth periods. Most sex-related QTLs were detected at LG 21 with a linkage span of 70.882 cM. Additionally, a small number of QTLs with high feasibility and a narrow R2 distribution were also observed on LG7 and LG14, suggesting that multi LGs or chromosomes might be involved in sex determination. High homology was recorded between LG21 in Cynoglossus semilaevis and turbot. This high-saturated turbot RAD-Seq linkage map is undoubtedly a promising platform for marker assisted selection (MAS) and flatfish genomics research.

  17. Multi-dimensional discovery of biomarker and phenotype complexes

    Directory of Open Access Journals (Sweden)

    Huang Kun

    2010-10-01

    Full Text Available Abstract Background Given the rapid growth of translational research and personalized healthcare paradigms, the ability to relate and reason upon networks of bio-molecular and phenotypic variables at various levels of granularity in order to diagnose, stage and plan treatments for disease states is highly desirable. Numerous techniques exist that can be used to develop networks of co-expressed or otherwise related genes and clinical features. Such techniques can also be used to create formalized knowledge collections based upon the information incumbent to ontologies and domain literature. However, reports of integrative approaches that bridge such networks to create systems-level models of disease or wellness are notably lacking in the contemporary literature. Results In response to the preceding gap in knowledge and practice, we report upon a prototypical series of experiments that utilize multi-modal approaches to network induction. These experiments are intended to elicit meaningful and significant biomarker-phenotype complexes spanning multiple levels of granularity. This work has been performed in the experimental context of a large-scale clinical and basic science data repository maintained by the National Cancer Institute (NCI funded Chronic Lymphocytic Leukemia Research Consortium. Conclusions Our results indicate that it is computationally tractable to link orthogonal networks of genes, clinical features, and conceptual knowledge to create multi-dimensional models of interrelated biomarkers and phenotypes. Further, our results indicate that such systems-level models contain interrelated bio-molecular and clinical markers capable of supporting hypothesis discovery and testing. Based on such findings, we propose a conceptual model intended to inform the cross-linkage of the results of such methods. This model has as its aim the identification of novel and knowledge-anchored biomarker-phenotype complexes.

  18. Fine mapping under linkage peaks for symptomatic or asymptomatic outcomes of Leishmania infantum infection in Brazil.

    Science.gov (United States)

    Weirather, Jason L; Duggal, Priya; Nascimento, Eliana L; Monteiro, Gloria R; Martins, Daniella R; Lacerda, Henio G; Fakiola, Michaela; Blackwell, Jenefer M; Jeronimo, Selma M B; Wilson, Mary E

    2016-09-01

    Infection with the protozoan Leishmania infantum can lead to asymptomatic infection and protective immunity, or to the progressive and potentially fatal disease visceral leishmaniasis (VL). Published studies show host genetic background determines in part whether infected individuals will develop a symptomatic or asymptomatic outcome. The purpose of the current study was to fine map chromosome regions previously linked with risk for symptomatic (chromosome 9) or asymptomatic (chromosomes 15 and 19) manifestations of L. infantum infection. We conducted a family-based genetic study of VL and asymptomatic infection (detected by a DTH skin test) with a final post quality control sample of 961 individuals with full genotype and phenotype information from highly endemic neighborhoods of northeast Brazil. A total of 5485 SNPs under the linkage peaks on chromosomes 9, 15 and 19 were genotyped. No strong SNP associations were observed for the DTH phenotype. The most significant associations with the VL phenotype were with SNP rs1470217 (p=5.9e-05; pcorrected=0.057) on chromosome 9, and with SNP rs8107014 (p=1.4e-05; pcorrected=0.013) on chromosome 19. SNP rs1470217 is situated in a 180kb intergenic region between TMEM215 (Transmembrane protein 215) and APTX (Aprataxin). SNP rs8107014 lies in the intron between exons 26 and 27 of a 34 exon transcript (ENST00000204005) of LTBP4, (Latent transforming growth factor-beta-binding protein 4a). The latter supports growing evidence that the transforming growth factor-beta pathway is important in the immunopathogenesis of VL. PMID:27155051

  19. Robust estimation of Cronbach's alpha

    OpenAIRE

    2002-01-01

    Cronbach’s alpha is a popular method to measure reliability, e.g. in quantifying the reliability of a score to summarize the information of several items in questionnaires. The alpha coefficient is known to be non-robust. We study the behavior of this coefficient in different settings to identify situations, which can easily occur in practice, but under which the Cronbach’s alpha coefficient is extremely sensitive to violations of the classical model assumptions. Furthermore, we construct a r...

  20. [beta]-hexosaminidase isozymes from cells cotransfected with [alpha] and [beta] cDNA constructs: Analysis of the [alpha]-subunit missense mutation associated with the adult form of Tay-Sachs disease

    Energy Technology Data Exchange (ETDEWEB)

    Brown, C.A.; Mahuran, D.J. (Univ. of Toronto (Canada))

    1993-08-01

    In vitro mutagenesis and transient expression in COS cells has been used to associate a missense mutation with a clinical or biochemical phenotype. Mutations affecting the [alpha]-subunit of [beta]-hexosaminidase A ([alpha][beta]) (E.C.3.2.1.52) result in Tay-Sachs disease. Because hexosaminidase A is heterodimeric, analysis of [alpha]-chain mutations is not straightforward. The authors examine three approaches utilizing previously identified mutations affecting [alpha]-chain folding. These involve transfection of (1) the [alpha] cDNA alone; (2) a [beta] cDNA construct encoding a [beta]-subunit substituted at a position homologous to that of the [alpha]-subunit, and (3) both [alpha] and [beta] cDNAs. The latter two procedures amplified residual activity levels over that of patient samples, an effect not previously found with mutations affecting an [open quotes]active[close quotes] [alpha]Arg residue. This effect may help to discriminate between protein-folding and active-site mutations. The authors conclude that, with proper controls, the latter method of cotransfection can be used to evaluate the effects and perhaps to predict the clinical course of some [alpha]-chain mutations. Using this technique, they demonstrate that the adult-onset Tay-Sachs mutation, [alpha]Gly[yields]Ser[sup 269], does not directly affect [alpha][beta] dimerization but exerts an indirect effect on the dimer through destabilizing the folded [alpha]-subunit at physiological temperatures. Two other [alpha] mutations linked to more severe phenotypes appear to inhibit the initial folding of the subunit. 36 refs., 2 figs., 5 tabs.

  1. Combined RAPD and RFLP molecular linkage map of asparagus.

    Science.gov (United States)

    Jiang, C; Lewis, M E; Sink, K C

    1997-02-01

    Two linkage maps of asparagus (Asparagus officinalis L.) were constructed using a double pseudotestcross mapping strategy with restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNAs (RAPDs), and allozymes as markers in a population generated from crossing MW25 x A19, two heterozygous parents. All data were inverted and combined with the natural data to detect linkages in repulsion phase. Two sets of data, one for each parent, were formed according to the inheritance patterns of the markers. The maternal MW25 map has a total of 163 marker loci placed in 13 linkage groups covering 1281 cM, with an average and a maximum distance between adjacent loci of 7.9 and 29 cM, respectively. The paternal A19 map has 183 marker loci covering 1324 cM in 9 linkage groups, with an average and a maximum distance between two adjacent loci of 7.7 and 29 cM, respectively. Six multiallelic RFLPs segregating in the pattern a/c x b/c and eight heterozygous loci (four RAPDs, and four RFLPs segregating in the pattern a/b x a/b (HZ loci)) were common to both maps. These 14 loci were used as bridges to align homologous groups between the two maps. In this case, RFLPs were more frequent and informative than RAPDs. Nine linkage groups in the MW25 map were homologous to six groups in the A19 map. In two cases, two or more bridge loci were common to a group; thus, the orientation of homologous linkage groups was also determined. In four other cases, only one locus was common to the two homologous groups and the orientation was unknown. Mdh, four RFLPs, and 14 RAPDs were assigned to chromosome L5, which also has the sex locus M. PMID:18464808

  2. Software for analysis and manipulation of genetic linkage data.

    Science.gov (United States)

    Weaver, R; Helms, C; Mishra, S K; Donis-Keller, H

    1992-06-01

    We present eight computer programs written in the C programming language that are designed to analyze genotypic data and to support existing software used to construct genetic linkage maps. Although each program has a unique purpose, they all share the common goals of affording a greater understanding of genetic linkage data and of automating tasks to make computers more effective tools for map building. The PIC/HET and FAMINFO programs automate calculation of relevant quantities such as heterozygosity, PIC, allele frequencies, and informativeness of markers and pedigrees. PREINPUT simplifies data submissions to the Centre d'Etude du Polymorphisme Humain (CEPH) data base by creating a file with genotype assignments that CEPH's INPUT program would otherwise require to be input manually. INHERIT is a program written specifically for mapping the X chromosome: by assigning a dummy allele to males, in the nonpseudoautosomal region, it eliminates falsely perceived noninheritances in the data set. The remaining four programs complement the previously published genetic linkage mapping software CRI-MAP and LINKAGE. TWOTABLE produces a more readable format for the output of CRI-MAP two-point calculations; UNMERGE is the converse to CRI-MAP's merge option; and GENLINK and LINKGEN automatically convert between the genotypic data file formats required by these packages. All eight applications read input from the same types of data files that are used by CRI-MAP and LINKAGE. Their use has simplified the management of data, has increased knowledge of the content of information in pedigrees, and has reduced the amount of time needed to construct genetic linkage maps of chromosomes. PMID:1598906

  3. Software for analysis and manipulation of genetic linkage data.

    Science.gov (United States)

    Weaver, R; Helms, C; Mishra, S K; Donis-Keller, H

    1992-06-01

    We present eight computer programs written in the C programming language that are designed to analyze genotypic data and to support existing software used to construct genetic linkage maps. Although each program has a unique purpose, they all share the common goals of affording a greater understanding of genetic linkage data and of automating tasks to make computers more effective tools for map building. The PIC/HET and FAMINFO programs automate calculation of relevant quantities such as heterozygosity, PIC, allele frequencies, and informativeness of markers and pedigrees. PREINPUT simplifies data submissions to the Centre d'Etude du Polymorphisme Humain (CEPH) data base by creating a file with genotype assignments that CEPH's INPUT program would otherwise require to be input manually. INHERIT is a program written specifically for mapping the X chromosome: by assigning a dummy allele to males, in the nonpseudoautosomal region, it eliminates falsely perceived noninheritances in the data set. The remaining four programs complement the previously published genetic linkage mapping software CRI-MAP and LINKAGE. TWOTABLE produces a more readable format for the output of CRI-MAP two-point calculations; UNMERGE is the converse to CRI-MAP's merge option; and GENLINK and LINKGEN automatically convert between the genotypic data file formats required by these packages. All eight applications read input from the same types of data files that are used by CRI-MAP and LINKAGE. Their use has simplified the management of data, has increased knowledge of the content of information in pedigrees, and has reduced the amount of time needed to construct genetic linkage maps of chromosomes.

  4. Shared receptor components but distinct complexes for alpha and beta interferons.

    Science.gov (United States)

    Lewerenz, M; Mogensen, K E; Uzé, G

    1998-09-25

    The type I interferon family includes 13 alpha, one omega and one beta subtypes recognized by a complex containing the receptor subunits ifnar1 and ifnar2 and their associated Janus tyrosine kinases, Tyk2 and Jak1. To investigate the reported differences in the way that alpha and beta interferons signal through the receptor, we introduced alanine-substitutions in the ifnar2 extracellular domain, and expressed the mutants in U5A cells, lacking endogenous ifnar2. A selection, designed to recover mutants that responded preferentially to alpha or beta interferon yielded three groups: I, neutral; II, sensitive to alpha interferon, partially resistant to beta interferon; III, resistant to alpha interferon, partially sensitive to beta interferon. A mutant clone, TMK, fully resistant to alpha interferon with good sensitivity to beta interferon, was characterized in detail and compared with U5A cells complemented with wild-type ifnar2 and also with Tyk2-deficient 11.1 cells, which exhibit a similar alpha-unresponsive phenotype with a partial beta interferon response. Using anti-receptor antibodies and mutant forms of beta interferon, three distinct modes of ligand interaction could be discerned: (i) alpha interferon with ifnar1 and ifnar2; (ii) beta interferon with ifnar1 and ifnar2; (iii) beta interferon with ifnar2 alone. We conclude that alpha and beta interferons signal differently through their receptors because the two ligand subtypes interact with the receptor subunits ifnar 1 and ifnar2 in entirely different ways.

  5. Genome-wide scan for serum ghrelin detects linkage on chromosome 1p36 in Hispanic children: results from the Viva La Familia study.

    Science.gov (United States)

    Voruganti, V Saroja; Göring, Harald H H; Diego, Vincent P; Cai, Guowen; Mehta, Nitesh R; Haack, Karin; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

    2007-10-01

    This study was conducted to investigate genetic influence on serum ghrelin and its relationship with adiposity-related phenotypes in Hispanic children (n=1030) from the Viva La Familia study (VFS). Anthropometric measurements and levels of serum ghrelin were estimated and genetic analyses conducted according to standard procedures. Mean age, body mass index (BMI), and serum ghrelin were 11+/-0.13 y, 25+/-0.24 kg/m2 and 38+/-0.5 ng/mL, respectively. Significant heritabilities (p<0.001) were obtained for BMI, weight, fat mass, percent fat, waist circumference, waist-to-height ratio, and ghrelin. Bivariate analyses of ghrelin with adiposity traits showed significant negative genetic correlations (p<0.0001) with weight, BMI, fat mass, percent fat, waist circumference, and waist-to-height ratio. A genome-wide scan for ghrelin detected significant linkage on chromosome 1p36.2 between STR markers D1S2697 and D1S199 (LOD=3.2). The same region on chromosome 1 was the site of linkage for insulin (LOD=3.3), insulinlike growth factor binding protein 1 (IGFBP1) (LOD=3.4), homeostatic model assessment method (HOMA) (LOD=2.9), and C-peptide (LOD=2.0). Several family-based studies have reported linkages for obesity-related phenotypes in the region of 1p36. These results indicate the importance of this region in relation to adiposity in children from the VFS.

  6. A Sequence-Tagged Linkage Map of Brassica rapa

    OpenAIRE

    Kim, Jung Sun; Chung, Tae Young; King, Graham J; Jin, Mina; Yang, Tae-Jin; Jin, Yong-Moon; Kim, Ho-Il; Park, Beom-Seok

    2006-01-01

    A detailed genetic linkage map of Brassica rapa has been constructed containing 545 sequence-tagged loci covering 1287 cM, with an average mapping interval of 2.4 cM. The loci were identified using a combination of 520 RFLP and 25 PCR-based markers. RFLP probes were derived from 359 B. rapa EST clones and amplification products of 11 B. rapa and 26 Arabidopsis. Including 21 SSR markers provided anchors to previously published linkage maps for B. rapa and B. napus and is followed as the refere...

  7. Linkage intensity learning approach with genetic algorithm for causality diagram

    Institute of Scientific and Technical Information of China (English)

    WANG Cheng-liang; CHEN Juan-juan

    2007-01-01

    The causality diagram theory, which adopts graphical expression of knowledge and direct intensity of causality, overcomes some shortages in belief network and has evolved into a mixed causality diagram methodology for discrete and continuous variable. But to give linkage intensity of causality diagram is difficult, particularly in many working conditions in which sampling data are limited or noisy. The classic learning algorithm is hard to be adopted. We used genetic algorithm to learn linkage intensity from limited data. The simulation results demonstrate that this algorithm is more suitable than the classic algorithm in the condition of sample shortage such as space shuttle's fault diagnoisis.

  8. Kinematical analysis on the several linkage drives for mechanical presses

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Kyung Chun; Jang, Dong Hwan [Inha Technical College, Incheon (Korea, Republic of)

    2009-02-15

    In this paper, a kinematical analysis is preformed to see mechanical characteristics of various linkage drives for a mechanical press. Mechanical characteristics of conventional and newly designed drives are investigated and compared in terms of slide velocity, productivity, load capacity and possible work-piece size. A crank-slider mechanism with arc crank-pin guide is introduced and analyzed particularly for kinematical performance using kinematical analysis software. The new linkage drive turns out to be effective in terms of load and velocity characteristics and productivity. Kinematical performance also provides a basis for the proper selection of mechanical presses

  9. Robust vibration control of flexible linkage mechanisms using piezoelectric films

    Science.gov (United States)

    Liao, Wen-Hwei; Chou, Jyh-Horng; Horng, Ing-Rong

    1997-08-01

    Based on the state space model of the flexible linkage mechanism equipped with piezoelectric films, a robust control methodology for suppressing elastodynamic responses of the high-speed flexible linkage mechanism with linear time-varying parameter perturbations by employing an observer-based feedback controller is presented. The instability caused by the linear time-varying parameter perturbations and the instability caused by the combined effect of control and observation spillover are investigated and carefully prevented by two robust stability criteria proposed in this paper. Numerical simulation of a slider - crank mechanism example is performed to evaluate the improvement of the elastodynamic responses.

  10. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

    Science.gov (United States)

    Szatmari, Peter; Paterson, Andrew; Zwaigenbaum, Lonnie; Roberts, Wendy; Brian, Jessica; Liu, Xiao-Qing; Vincent, John; Skaug, Jennifer; Thompson, Ann; Senman, Lili; Feuk, Lars; Qian, Cheng; Bryson, Susan; Jones, Marshall; Marshall, Christian; Scherer, Stephen; Vieland, Veronica; Bartlett, Christopher; Mangin, La Vonne; Goedken, Rhinda; Segre, Alberto; Pericak-Vance, Margaret; Cuccaro, Michael; Gilbert, John; Wright, Harry; Abramson, Ruth; Betancur, Catalina; Bourgeron, Thomas; Gillberg, Christopher; Leboyer, Marion; Buxbaum, Joseph; Davis, Kenneth; Hollander, Eric; Silverman, Jeremy; Hallmayer, Joachim; Lotspeich, Linda; Sutcliffe, James; Haines, Jonathan; Folstein, Susan; Piven, Joseph; Wassink, Thomas; Sheffield, Val; Geschwind, Daniel; Bucan, Maja; Brown, Ted; Cantor, Rita; Constantino, John; Gilliam, Conrad; Herbert, Martha; Lajonchere, Clara; Ledbetter, David; Lese-Martin, Christa; Miller, Janet; Nelson, Stan; Samango-Sprouse, Carol; Spence, Sarah; State, Matthew; Tanzi, Rudolph; Coon, Hilary; Dawson, Geraldine; Devlin, Bernie; Estes, Annette; Flodman, Pamela; Klei, Lambertus; Mcmahon, William; Minshew, Nancy; Munson, Jeff; Korvatska, Elena; Rodier, Patricia; Schellenberg, Gerard; Smith, Moyra; Spence, Anne; Stodgell, Chris; Tepper, Ping Guo; Wijsman, Ellen; Yu, Chang-En; Rogé, Bernadette; Mantoulan, Carine; Wittemeyer, Kerstin; Poustka, Annemarie; Felder, Bärbel; Klauck, Sabine; Schuster, Claudia; Poustka, Fritz; Bölte, Sven; Feineis-Matthews, Sabine; Herbrecht, Evelyn; Schmötzer, Gabi; Tsiantis, John; Papanikolaou, Katerina; Maestrini, Elena; Bacchelli, Elena; Blasi, Francesca; Carone, Simona; Toma, Claudio; Van Engeland, Herman; De Jonge, Maretha; Kemner, Chantal; Koop, Frederieke; Langemeijer, Marjolein; Hijmans, Channa; Staal, Wouter; Baird, Gillian; Bolton, Patrick; Rutter, Michael; Weisblatt, Emma; Green, Jonathan; Aldred, Catherine; Wilkinson, Julie-Anne; Pickles, Andrew; Le Couteur, Ann; Berney, Tom; Mcconachie, Helen; Bailey, Anthony; Francis, Kostas; Honeyman, Gemma; Hutchinson, Aislinn; Parr, Jeremy; Wallace, Simon; Monaco, Anthony; Barnby, Gabrielle; Kobayashi, Kazuhiro; Lamb, Janine; Sousa, Ines; Sykes, Nuala; Cook, Edwin; Guter, Stephen; Leventhal, Bennett; Salt, Jeff; Lord, Catherine; Corsello, Christina; Hus, Vanessa; Weeks, Daniel; Volkmar, Fred; Tauber, Maïté; Fombonne, Eric; Shih, Andy; Meyer, Kacie

    2007-01-01

    Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with ≥ 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. PMID:17322880

  11. A Family with Mental Retardation, Epilepsy and Cerebellar Hypoplasia Showing Linkage to Chromosome 20p11.21-q11.23

    Directory of Open Access Journals (Sweden)

    Fatih Bayrakli

    2014-01-01

    Full Text Available Background: Cerebellar hypoplasia (CH is a rare malformation caused by various etiologies, usually manifesting clinically as nonprogressive cerebellar ataxia with or without mental retardation. The molecular pathogenesis of the autosomal recessive cerebellar ataxias has a wide range of mechanisms. Differential diagnosis and categorization of the recessive cerebellar ataxias, however, need more specific, biochemical and genetic investigation. Methods: This study applied whole-genome linkage analysis to study a family with nonprogressive cerebellar ataxia and additional mental retardation, epilepsy, and facial dysmorphic features. Genotyping and linkage analysis was done using the GeneChip Mapping 250K NspI Array (Affymetrix Inc., Santa Clara, Calif., USA for genome-wide linkage analysis of the genotyping data from the affected children and their parents. Results: Allegro software version 1.2 was used for multipoint linkage analysis. We assumed an autosomal recessive inheritance pattern and assigned a penetrance of 0.999. Single-nucleotide polymorphism allele frequencies were estimated from the Affymetrix data of the Caucasian family studied. Using these parameters, a theoretical maximum logarithm of the odds score of 2.69 was identified at chromosome 20p11.21-q11.23. Conclusions: This chromosomal locus is unprecedented in autosomal recessive and nonprogressive ataxia disorder. Further investigation might reveal a new causative gene generating the CH phenotype.

  12. PDFs, $\\alpha_s$, and quark masses from global fits

    CERN Document Server

    Alekhin, S; Moch, S; Placakyte, R

    2016-01-01

    The strong coupling constant $\\alpha_s$ and the heavy-quark masses, $m_c$, $m_b$, $m_t$ are extracted simultaneosly with the parton distribution functions (PDFs) in the updated ABM12 fit including recent data from CERN-SPS, HERA, Tevatron, and the LHC. The values of \\begin{eqnarray} \

  13. The influence of internal stresses on the fracture toughness of {alpha}/{beta} titanium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Helbert, A.L.; Feaugas, X.; Clavel, M.

    1999-11-01

    The influence of internal stresses on fracture toughness was investigated in {alpha}/{beta} titanium alloys. It was shown that the direct linkage of K{sub IC} to various microstructural parameters was not so conclusive, since the different parameters act simultaneously on fracture toughness. On the contrary, the metallurgical parameters change the plastic strain incompatibilities inside the material. Thus X, which is a macroscopic measurement of these incompatibilities, is the relevant parameter to account for the different metallurgical influences on toughness. The influence on X of the {alpha}-phase percentage, aspect ratio, and the secondary {alpha}-phase percentage was determined, and it was established that low internal stresses could provide high fracture toughness. The present work also showed the ability of a modified Gurson-Tvergaard (GT) model to calculate the experimental K{sub IC} value.

  14. Modifier Genes for Mouse Phosphatidylinositol Transfer Protein alpha (vibrator) That Bypass Juvenile Lethality

    NARCIS (Netherlands)

    Concepcion, Dorothy; Johannes, Frank; Lo, Yuan Hung; Yao, Jay; Fong, Jerry; Hamilton, Bruce A.

    2011-01-01

    Phosphatidylinositol transfer proteins (PITPs) mediate lipid signaling and membrane trafficking in eukaryotic cells. Loss-of-function mutations of the gene encoding PITP alpha in mice result in a range of dosage-sensitive phenotypes, including neurological dysfunction, neurodegeneration, and prematu

  15. Chromosomal phenotypes and submicroscopic abnormalities

    Directory of Open Access Journals (Sweden)

    Devriendt Koen

    2004-01-01

    Full Text Available Abstract The finding, during the last decade, that several common, clinically delineated syndromes are caused by submicroscopic deletions or, more rarely, by duplications, has provided a powerful tool in the annotation of the human genome. Since most microdeletion/microduplication syndromes are defined by a common deleted/duplicated region, abnormal dosage of genes located within these regions can explain the phenotypic similarities among individuals with a specific syndrome. As such, they provide a unique resource towards the genetic dissection of complex phenotypes such as congenital heart defects, mental and growth retardation and abnormal behaviour. In addition, the study of phenotypic differences in individuals with the same microdeletion syndrome may also become a treasury for the identification of modifying factors for complex phenotypes. The molecular analysis of these chromosomal anomalies has led to a growing understanding of their mechanisms of origin. Novel tools to uncover additional submicroscopic chromosomal anomalies at a higher resolution and higher speed, as well as the novel tools at hand for deciphering the modifying factors and epistatic interactors, are 'on the doorstep' and will, besides their obvious diagnostic role, play a pivotal role in the genetic dissection of complex phenotypes.

  16. Alpha glucosidase inhibitors.

    Science.gov (United States)

    Kalra, Sanjay

    2014-04-01

    Alpha glucosidase inhibitors (AGIs) are a unique class of anti-diabetic drugs. Derived from bacteria, these oral drugs are enzyme inhibitors which do not have a pancreato -centred mechanism of action. Working to delay carbohydrate absorption in the gastrointestinal tract, they control postprandial hyperglycaemia and provide unquestioned cardiovascular benefit. Specially suited for a traditional Pakistani carbohydrate-rich diet, AGIs have been termed the 'untapped diamonds' of diabetology. The use of these oral antidiabetic drugs (OADs) that target pathophysiology in the early stages of type 2 diabetes, notably to reduce postprandial hyperglycaemia and hyperinsulinaemia will inevitably increase with time. This review describes the history of their development, mechanism of action, basic and clinical pharmacology, and suggests practical, evidence-based guidance for their optimal use. PMID:24864650

  17. Molecular studies of linkage group XIX of Chlamydomonas reinhardtii: evidence against a basal body location

    OpenAIRE

    1991-01-01

    Linkage group XIX (also known as the UNI linkage group) in the green alga, Chlamydomonas reinhardtii, exhibits a number of unusual properties that have lead to the suggestion that it represents a basal body-associated chromosome. To begin a molecular analysis of this linkage group, we have identified DNA sequences from it and used them to determine the copy number of linkage group XIX within the cell. We find that linkage group XIX is present in the same copy number per cell as nuclear linkag...

  18. Empirical aspects of record linkage across multiple data sets using statistical linkage keys: the experience of the PIAC cohort study

    Directory of Open Access Journals (Sweden)

    Gibson Diane

    2010-02-01

    Full Text Available Abstract Background In Australia, many community service program data collections developed over the last decade, including several for aged care programs, contain a statistical linkage key (SLK to enable derivation of client-level data. In addition, a common SLK is now used in many collections to facilitate the statistical examination of cross-program use. In 2005, the Pathways in Aged Care (PIAC cohort study was funded to create a linked aged care database using the common SLK to enable analysis of pathways through aged care services. Linkage using an SLK is commonly deterministic. The purpose of this paper is to describe an extended deterministic record linkage strategy for situations where there is a general person identifier (e.g. an SLK and several additional variables suitable for data linkage. This approach can allow for variation in client information recorded on different databases. Methods A stepwise deterministic record linkage algorithm was developed to link datasets using an SLK and several other variables. Three measures of likely match accuracy were used: the discriminating power of match key values, an estimated false match rate, and an estimated step-specific trade-off between true and false matches. The method was validated through examining link properties and clerical review of three samples of links. Results The deterministic algorithm resulted in up to an 11% increase in links compared with simple deterministic matching using an SLK. The links identified are of high quality: validation samples showed that less than 0.5% of links were false positives, and very few matches were made using non-unique match information (0.01%. There was a high degree of consistency in the characteristics of linked events. Conclusions The linkage strategy described in this paper has allowed the linking of multiple large aged care service datasets using a statistical linkage key while allowing for variation in its reporting. More widely, our

  19. Genome-wide linkage scan for factors of metabolic syndrome in a Chinese population

    Directory of Open Access Journals (Sweden)

    Chan Juliana CN

    2010-02-01

    Full Text Available Abstract Background Shared genetic factors may contribute to the phenotypic clustering of different components of the metabolic syndrome (MES. This study aims to identify genetic loci that contribute to individual or multiple factors related to MES. Results We studied 478 normoglycemic subjects ascertained through 163 families participating in the Hong Kong Family Diabetes Study. Factor analysis on 15 MES-related traits yielded 6 factors including adiposity factor (body mass index, waist and hip circumferences, insulin factor (fasting insulin and insulin AUC during OGTT, glucose factor (fasting glucose and glucose AUC during OGTT, TC-LDLC factor (total cholesterol and LDL-cholesterol, blood pressure factor (systolic and diastolic blood pressure and TG-HDLC factor (triglycerides and HDL-cholesterol. Genome-wide linkage analyses were performed on these factors using variance component approach. Suggestive evidence for linkage (LOD = 1.24 - 2.46 were observed for adiposity factor (chromosome 1 at 187 cM, chromosome 9 at 34 cM and chromosome 17 at 10 cM, insulin factor (chromosome 2 at 128 cM, chromosome 5 at 21 cM and chromosome 12 at 7 cM, glucose factor (chromosome 7 at 155 cM, TC-LDLC factor (chromosome 7 at 151 cM and chromosome 13 at 15 cM and TG-HDLC factor (chromosome 7 at 155 cM. Conclusions In summary, our findings suggest the presence of susceptibility loci that influence either single (chromosomes 1, 2, 5, 9, 12, 13 and 17 or multiple factors (chromosome 7 for MES in Hong Kong Chinese without diabetes.

  20. Genetic diversity and linkage disequilibrium analysis in elite sugar beet breeding lines and wild beet accessions.

    Science.gov (United States)

    Adetunji, Ibraheem; Willems, Glenda; Tschoep, Hendrik; Bürkholz, Alexandra; Barnes, Steve; Boer, Martin; Malosetti, Marcos; Horemans, Stefaan; van Eeuwijk, Fred

    2014-03-01

    Linkage disequilibrium decay in sugar beet is strongly affected by the breeding history, and varies extensively between and along chromosomes, allowing identification of known and unknown signatures of selection. Genetic diversity and linkage disequilibrium (LD) patterns were investigated in 233 elite sugar beet breeding lines and 91 wild beet accessions, using 454 single nucleotide polymorphisms (SNPs) and 418 SNPs, respectively. Principal coordinate analysis suggested the existence of three groups of germplasm, corresponding to the wild beets, the seed parent and the pollen parent breeding pool. LD was investigated in each of these groups, with and without correction for genetic relatedness. Without correction for genetic relatedness, in the pollen as well as the seed parent pool, LD persisted beyond 50 centiMorgan (cM) on four (2, 3, 4 and 5) and three chromosomes (2, 4 and 6), respectively; after correction for genetic relatedness, LD decayed after wild beet accessions, there was a strong LD decay: on average LD disappeared after 1 cM when LD was calculated with a correction for genetic relatedness. Persistence of LD was not only observed between distant SNPs on the same chromosome, but also between SNPs on different chromosomes. Regions on chromosomes 3 and 4 that harbor disease resistance and monogermy loci showed strong genetic differentiation between the pollen and seed parent pools. Other regions, on chromosomes 8 and 9, for which no a priori information was available with respect to their contribution to the phenotype, still contributed to clustering of lines in the elite breeding material. PMID:24292512

  1. Absence of linkage between MHC and a gene involved in susceptibility to human schistosomiasis

    Directory of Open Access Journals (Sweden)

    Chiarella J.M.

    1998-01-01

    Full Text Available Six hundred million people are at risk of infection by Schistosoma mansoni. MHC haplotypes have been reported to segregate with susceptibility to schistosomiasis in murine models. In humans, a major gene related to susceptibility/resistance to infection by S. mansoni (SM1 and displaying the mean fecal egg count as phenotype was detected by segregation analysis. This gene displayed a codominant mode of inheritance with an estimated frequency of 0.20-0.25 for the deleterious allele and accounted for more than 50% of the variance of infection levels. To determine if the SM1 gene segregates with the human MHC chromosomal region, we performed a linkage study by the lod score method. We typed for HLA-A, B, C, DR and DQ antigens in 11 informative families from an endemic area for schistosomiasis in Bahia, Brazil, by the microlymphocytotoxicity technique. HLA-DR typing by the polymerase chain reaction with sequence-specific primers (PCR-SSP and HLA-DQ were confirmed by PCR-sequence-specific oligonucleotide probes (PCR-SSOP. The lod scores for the different q values obtained clearly indicate that there is no physical linkage between HLA and SM1 genes. Thus, susceptibility or resistance to schistosomiasis, as defined by mean fecal egg count, is not primarily dependent on the host's HLA profile. However, if the HLA molecule plays an important role in specific immune responses to S. mansoni, this may involve the development of the different clinical aspects of the disease such as granuloma formation and development of hepatosplenomegaly.

  2. Alpha particle emitters in medicine

    International Nuclear Information System (INIS)

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 (211At) and natural bismuth-212 (212Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 (223Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs

  3. The Lyman alpha reference sample

    DEFF Research Database (Denmark)

    Hayes, M.; Östlin, G.; Schaerer, D.;

    2013-01-01

    We report on new imaging observations of the Lyman alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028

  4. Alpha particle emitters in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.R.

    1989-09-01

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 ({sup 211}At) and natural bismuth-212 ({sup 212}Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 ({sup 223}Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs.

  5. Using whole-genome sequence data to predict quantitative trait phenotypes in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Ulrike Ober

    Full Text Available Predicting organismal phenotypes from genotype data is important for plant and animal breeding, medicine, and evolutionary biology. Genomic-based phenotype prediction has been applied for single-nucleotide polymorphism (SNP genotyping platforms, but not using complete genome sequences. Here, we report genomic prediction for starvation stress resistance and startle response in Drosophila melanogaster, using ∼2.5 million SNPs determined by sequencing the Drosophila Genetic Reference Panel population of inbred lines. We constructed a genomic relationship matrix from the SNP data and used it in a genomic best linear unbiased prediction (GBLUP model. We assessed predictive ability as the correlation between predicted genetic values and observed phenotypes by cross-validation, and found a predictive ability of 0.239±0.008 (0.230±0.012 for starvation resistance (startle response. The predictive ability of BayesB, a Bayesian method with internal SNP selection, was not greater than GBLUP. Selection of the 5% SNPs with either the highest absolute effect or variance explained did not improve predictive ability. Predictive ability decreased only when fewer than 150,000 SNPs were used to construct the genomic relationship matrix. We hypothesize that predictive power in this population stems from the SNP-based modeling of the subtle relationship structure caused by long-range linkage disequilibrium and not from population structure or SNPs in linkage disequilibrium with causal variants. We discuss the implications of these results for genomic prediction in other organisms.

  6. Can University-Industry Linkages Stimulate Student Employability?

    Science.gov (United States)

    Ishengoma, Esther; Vaaland, Terje I.

    2016-01-01

    Purpose: The purpose of this paper is to identify important university-industry linkage (UIL) activities that can stimulate the likelihood of employability among students. Design/methodology/approach: A total of 404 respondents located in Tanzania, comprising students, faculty members and employees from 20 companies operating within the oil and…

  7. Linkage disequilibrium in young genetically isolated Dutch population

    NARCIS (Netherlands)

    Y.S. Aulchenko (Yurii); P. Heutink (Peter); I. Mackay (Ian); A.M. Bertoli Avella (Aida); J. Pullen (Jan); N. Vaessen (Norbert); T.A.M. Rademaker (Tessa); L.A. Sandkuijl (Lodewijk); L. Cardon (Lon); C.M. van Duijn (Cock); B.A. Oostra (Ben)

    2004-01-01

    textabstractThe design and feasibility of genetic studies of complex diseases are critically dependent on the extent and distribution of linkage disequilibrium (LD) across the genome and between different populations. We have examined genomewide and region-specific LD in a young genetically isolated

  8. Genetic linkage study of bipolar disorder and the serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Kelsoe, J.R.; Morison, M.; Mroczkowski-Parker, Z.; Bergesch, P.; Rapaport, M.H.; Mirow, A.L. [Univ. of California, San Diego, CA (United States)] [and others

    1996-04-09

    The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Old Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter. 20 refs., 2 tabs.

  9. Linkage Disequilibrium Decay and Haplotype Block Structure in the Pig

    NARCIS (Netherlands)

    Amaral, A.J.; Megens, H.J.W.C.; Crooijmans, R.P.M.A.; Heuven, H.C.M.; Groenen, M.A.M.

    2008-01-01

    Linkage disequilibrium (LD) may reveal much about domestication and breed history. Ail investigation was conducted, to analyze the extent of LD, haploblock partitioning, and haplotype diversity within haploblocks across several pig breeds from China and Europe and in European wild boar. In total, 37

  10. Mapping organizational linkages in the agricultural innovation system of Azerbaijan

    NARCIS (Netherlands)

    Temel, T.

    2004-01-01

    This study describes the evolving context and organisational linkages in the agricultural innovation system of Azerbaijan and suggests ways to promote effective organisational ties for the development, distribution and use of new or improved information and knowledge related to agriculture. Graph-th

  11. Analysis of Linkage Effects among Currency Networks Using REER Data

    Directory of Open Access Journals (Sweden)

    Haishu Qiao

    2015-01-01

    Full Text Available We modeled the currency networks through the use of REER (real effective exchange rate instead of a bilateral exchange rate in order to overcome the confusion in selecting base currencies. Based on the MST (minimum spanning tree approach and the rolling-window method, we constructed time-varying and correlation-based networks with which we investigate the linkage effects among different currencies. In particular, and as the source of empirical data, we chose the monthly REER data for a set of 61 major currencies during the period from 1994 to 2014. The study demonstrated that obvious linkage effects existed among currency networks and the euro (EUR was confirmed as the predominant world currency. Additionally, we used the rolling-window method to investigate the stability of linkage effects, doing so by calculating the mean correlations and mean distances as well as the normalized tree length and degrees of those currencies. The results showed that financial crises during the study period had a great effect on the currency network’s topology structure and led to more clustered currency networks. Our results suggested that it is more appropriate to estimate the linkage effects among currency networks through the use of REER data.

  12. Association Between Pachytene Chromosomes and Linkage Groups in Carrot

    Science.gov (United States)

    The genome of carrot (Daucus carota L.) consists of ~ 480 Mb/1C organized in 9 chromosome pairs. The importance of carrots in human nutrition is triggering the development of genomic resources, including carrot linkage maps, a bacterial artificial chromosome (BAC) clone library and BAC end sequence...

  13. Recombination patterns reveal information about centromere location on linkage maps

    DEFF Research Database (Denmark)

    Limborg, Morten T.; McKinney, Garrett J.; Seeb, Lisa W.;

    2016-01-01

    . mykiss) characterized by low and unevenly distributed recombination – a general feature of male meiosis in many species. Further, a high frequency of double crossovers along chromosome arms in barley reduced resolution for locating centromeric regions on most linkage groups. Despite these limitations...

  14. Innovation and inter-firm linkages : new implications for policy

    NARCIS (Netherlands)

    Nooteboom, B

    1999-01-01

    This article discusses the implications for competition, innovation and learning of different forms of inter-firm linkage, ways to govern them, different 'generic systems' of innovation, and government policy. It employs a transformed theory of transactions that can deal with innovation and learning

  15. Low Cost Computer Graphics Simulation of Basic Kinematic Linkages.

    Science.gov (United States)

    Smith, Donald A.; Jacquot, Raymond G.

    1984-01-01

    Presents algorithms for the simulation and motion display of the three basic kinematic devices: (1) four bar linkages; (2) the slider crank; and (3) the inverted slider crank mechanisms. The algorithms were implemented on a Commodore-VIC 20 microcomputer system with 6500 bytes of available memory. (Author/JN)

  16. Monetary Policy with Sectoral Linkages and Durable Goods

    DEFF Research Database (Denmark)

    Petrella, Ivan; Rossi, Raffaele; Santoro, Emiliano

    We study the normative implications of a New Keynesian model featuring intersectoral trade of intermediate goods between two sectors that produce durables and non-durables. The interplay between durability and sectoral production linkages fundamentally alters the intersectoral stabilization trade...... are not properly accounted for by conventional measures of core inflation...

  17. Aglycone specificity of Escherichia coli alpha-xylosidase investigated by transxylosylation.

    Science.gov (United States)

    Kang, Min-Sun; Okuyama, Masayuki; Yaoi, Katsuro; Mitsuishi, Yasushi; Kim, Young-Min; Mori, Haruhide; Kim, Doman; Kimura, Atsuo

    2007-12-01

    The specificity of the aglycone-binding site of Escherichia coli alpha-xylosidase (YicI), which belongs to glycoside hydrolase family 31, was characterized by examining the enzyme's transxylosylation-catalyzing property. Acceptor specificity and regioselectivity were investigated using various sugars as acceptor substrates and alpha-xylosyl fluoride as the donor substrate. Comparison of the rate of formation of the glycosyl-enzyme intermediate and the transfer product yield using various acceptor substrates showed that glucose is the best complementary acceptor at the aglycone-binding site. YicI preferred aldopyranosyl sugars with an equatorial 4-OH as the acceptor substrate, such as glucose, mannose, and allose, resulting in transfer products. This observation suggests that 4-OH in the acceptor sugar ring made an essential contribution to transxylosylation catalysis. Fructose was also acceptable in the aglycone-binding site, producing two regioisomer transfer products. The percentage yields of transxylosylation products from glucose, mannose, fructose, and allose were 57, 44, 27, and 21%, respectively. The disaccharide transfer products formed by YicI, alpha-D-Xylp-(1-->6)-D-Manp, alpha-D-Xylp-(1-->6)-D-Fruf, and alpha-d-Xylp-(1-->3)-D-Frup, are novel oligosaccharides that have not been reported previously. In the transxylosylation to cello-oligosaccharides, YicI transferred a xylosyl moiety exclusively to a nonreducing terminal glucose residue by alpha-1,6-xylosidic linkages. Of the transxylosylation products, alpha-d-Xylp-(1-->6)-D-Manp and alpha-d-Xylp-(1-->6)-D-Fruf inhibited intestinal alpha-glucosidases. PMID:17970751

  18. Alpha Schottky junction energy source

    Science.gov (United States)

    Litz, Marc S.; Fan, Zhaoyang; Carroll, James J.; Bayne, Stephen

    2012-06-01

    Isotope batteries offer solutions for long-lived low-power sensor requirements. Alpha emitting isotopes have energy per decay 103 times that of beta emitters. Alpha particles are absorbed within 20 μm of most materials reducing shielding mitigation. However, damage to materials from the alphas limits their practical use. A Schottky Barrier Diode (SBD) geometry is considered with an alpha emitting contact-layer on a diamond-like crystal semiconductor region. The radiation tolerance of diamond, the safety of alpha particles, combined with the internal field of the SBD is expected to generate current useful for low-power electronic devices over decades. Device design parameters and calculations of the expected current are described.

  19. Development of a SNP resource and a genetic linkage map for Atlantic cod (Gadus morhua

    Directory of Open Access Journals (Sweden)

    Higgins Brent

    2010-03-01

    Full Text Available Abstract Background Atlantic cod (Gadus morhua is a species with increasing economic significance for the aquaculture industry. The genetic improvement of cod will play a critical role in achieving successful large-scale aquaculture. While many microsatellite markers have been developed in cod, the number of single nucleotide polymorphisms (SNPs is currently limited. Here we report the identification of SNPs from sequence data generated by a large-scale expressed sequence tag (EST program, focusing on fish originating from Canadian waters. Results A total of 97976 ESTs were assembled to generate 13448 contigs. We detected 4753 SNPs that met our selection criteria (depth of coverage ≥ 4 reads; minor allele frequency > 25%. 3072 SNPs were selected for testing. The percentage of successful assays was 75%, with 2291 SNPs amplifying correctly. Of these, 607 (26% SNPs were monomorphic for all populations tested. In total, 64 (4% of SNPs are likely to represent duplicated genes or highly similar members of gene families, rather than alternative alleles of the same gene, since they showed a high frequency of heterozygosity. The remaining polymorphic SNPs (1620 were categorised as validated SNPs. The mean minor allele frequency of the validated loci was 0.258 (± 0.141. Of the 1514 contigs from which validated SNPs were selected, 31% have a significant blast hit. For the SNPs predicted to occur in coding regions (141, we determined that 36% (51 are non-synonymous. Many loci (1033 SNPs; 64% are polymorphic in all populations tested. However a small number of SNPs (184 that are polymorphic in the Western Atlantic were monomorphic in fish tested from three European populations. A preliminary linkage map has been constructed with 23 major linkage groups and 924 mapped SNPs. Conclusions These SNPs represent powerful tools to accelerate the genetic improvement of cod aquaculture. They have been used to build a genetic linkage map that can be applied to

  20. Anonymous marker loci within 400 kb of HLA-A generate haplotypes in linkage disequilibrium with the hemochromatosis gene (HFE)

    Energy Technology Data Exchange (ETDEWEB)

    Yaouanq, J.; Perichon, M.; Treut, A.L.; Kahloun, A.E.; Mauvieux, V.; Blayau, M.; Jouanolle, A.M.; Chauvel, B.; Le Gall, J.Y.; David, V. (Faculte de Medicine, Rennes (France)) (and others)

    1994-02-01

    The hemochromatosis gene (HFE) maps to 6p21.3 and is less than 1 cM from the HLA class I gene; however, the precise physical location of the gene has remained elusive and controversial. The unambiguous identification of a crossover event within hemochromatosis families is very difficult; it is particularly hampered by the variability of the phenotypic expression as well as by the sex- and age-related penetrance of the disease. For these considerations, traditional linkage analysis could prove of limited value in further refining the extrapolated physical position of HFE. The authors therefore embarked upon a linkage-disequilibrium analysis of HFE and normal chromosomes for the Brittany population. In this report, 66 hemochromatosis families yielding 151 hemochromatosis chromosomes and 182 normal chromosomes were RFLP-typed with a battery of probes, including two newly derived polymorphic markers from the 6.7 and HLA-F loci located 150 and 250 kb telomeric to HLA-A, respectively. The results suggest a strong peak of existing linkage disequilibrium focused within the i82-to-6.7 interval (approximately 250 kb). The zone of linkage disequilibrium is flanked by the i97 locus, positioned 30 kb proximal to i82, and the HLA-F gene, found 250 kb distal to HLA-A, markers of which display no significant association with HFE. These data support the possibility that HFE resides within the 400-kb expanse of DNA between i97 and HLA-F. Alternatively, the very tight association of HLA-A3 and allele 1 of the 6.7 locus, both of which are comprised by the major ancestral or founder HFE haplotype in Brittany, supports the possibility that the disease gene may reside immediately telomeric to the 6.7 locus within the linkage-disequilibrium zone. Additionally, hemochromatosis haplotypes possessing HLA-A11 and the low-frequency HLA-F polymorphism (allele 2) are supportive of a separate founder chromosome containing a second, independently arising mutant allele. 69 refs., 1 fig., 5 tabs.

  1. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P;

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...

  2. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape cha

  3. Phenotypic spectrum of GABRA1

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Marini, Carla; Pfeffer, Siona;

    2016-01-01

    OBJECTIVE: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. METHODS: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analy...

  4. Raising cane: linkages, organizations and negotiations in Malang's sugar industry, East Java.

    NARCIS (Netherlands)

    Hartveld, A.J.

    1996-01-01

    The linkages between the Javanese sugar industry and the village communities have drawn the attention of both historians and social scientists. The formal organization of these linkages has changed drastically since Indonesia's independence; from plantation into outgrowers production contract system

  5. Document Fine Scale Linkage Areas and Conservation Delivery of the Northern Rockies in US and Canada

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Assessment of fine-scale habitat linkages in the Northern Rockies through use of biological DNA, telemetry and ecological modeling to predict critical linkages for...

  6. Juvenile spinal muscular atrophy: a new hexosaminidase deficiency phenotype.

    Science.gov (United States)

    Johnson, W G; Wigger, H J; Karp, H R; Glaubiger, L M; Rowland, L P

    1982-01-01

    A 24-year-old Ashkenazi Jewish man was evaluated for a nine-year history of progressive leg weakness with fasciculations. Electromyography, nerve conduction velocities, muscle biopsy, and serum creatine kinase were consistent with anterior horn cell disease. On rectal biopsy, ganglion cells were filled with membranous cytoplasmic bodies and an unusual submucosal layer of periodic acid-Schiff positive histiocytes filled with granules was seen. Hexosaminidase A in serum and leukocytes was severely decreased in the patient and partially decreased in parents and a brother. A paternal relative had classic infantile Tay-Sachs disease. Juvenile spinal muscular atrophy in this patient, closely resembling the Kugelberg-Welander phenotype, resulted from an alpha-locus hexosaminidase deficiency disorder, possibly a genetic compound of HEX alpha 2 and a milder hexosaminidase alpha-locus allele. Other cases of hexosaminidase deficiency have included anterior horn cell disease as part of a more complex disorder, but this is the first case, to our knowledge, of a hexosaminidase deficiency disorder presenting as spinal muscular atrophy. PMID:6460466

  7. Laser-assisted {alpha} decay

    Energy Technology Data Exchange (ETDEWEB)

    Castaneda Cortes, Hector Mauricio; Palffy, Adriana; Keitel, Christoph H. [Max-Planck-Institut fuer Kernphysik, Saupfercheckweg 1, 69117 Heidelberg (Germany); Popruzhenko, Sergey [Moscow State Engineering Physics Institute (Russian Federation)

    2012-07-01

    The spontaneous emission of alpha particles by unstable nuclei was one of the first physical processes to be described by quantum tunneling of a quasistationary state, i.e. a long-lived state. The development of new powerful coherent light sources opens the possibility to study the direct interaction between strong laser fields and atomic nuclei, assisting the tunneling of the {alpha} particle through the nuclear barrier. In this work we investigate for the first time the effect of strong laser fields on the tunneling and {alpha} particle emission of several medium-mass and heavy nuclei. To this end we make use of the formalism we have developed starting from the well-known Strong-Field Approximation and its complex trajectories formulation to describe the laser-assisted decay of quasistationary states [1]. The effect of a static as well as optical and X-ray monochromatic fields on the {alpha} decay lifetimes and {alpha} particle emission spectra is determined. We find that even at strong intensities, the laser-induced acceleration of the {alpha} decay is negligible, and only the spectra are significantly changed by the laser field. In particular, for optical fields, high laser intensities can lead to rescattering of the {alpha} particle off the daughter nucleus.

  8. Expression of transforming growth factor alpha in plutonium-239-induced lung neoplasms in dogs: investigations of autocrine mechanisms of growth

    International Nuclear Information System (INIS)

    We have previously shown that 47% of radiation-induced lung neoplasms in dogs exhibit increased expression of epidermal growth factor receptor (EGFR). In this study, we investigated the expression of transforming growth factor alpha (TGF-alpha), a ligand for EGFR, to determine if an autocrine mechanism for growth stimulation was present in these tumors. As determined by immunohistochemistry, 59% (26/44) of the lung neoplasms examined had increased expression of TGF-alpha. Expression of TGF-alpha was not related to the etiology of the tumor, e.g., spontaneous or plutonium-induced; however, it was related to the phenotype of the tumor. Statistical analysis of the correlation of EGFR and TGF-alpha expression within the same tumor did not show a positive association; however, specific phenotypes did have statistically significant expression of EGFR or TGF-alpha, suggesting that overexpression of either the ligand or its receptor conferred a growth advantage to the neoplasm. Twenty-seven percent (32/117) of radiation-induced proliferative epithelial foci expressed TGF-alpha, and a portion of those foci (8/32) expressed both EGFR and TGF-alpha. This supports the hypothesis that these foci represent preneoplastic lesions, and suggests that those foci exhibiting increased expression of the growth factor or its receptor are at greater risk for progressing to neoplasia

  9. ALPHA freezes antiprotons

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    Laboratories like CERN can routinely produce many different types of antiparticles. In 1995, the PS210 experiment formed the first antihydrogen atoms and a few years later, in 2002, ATRAP and ATHENA were already able to produce several thousand of them. However, no experiment in the world has succeeded in ‘trapping’ these anti-atoms in order to study them. This is the goal of the ALPHA experiment, which has recently managed to cool down the antiprotons to just a few Kelvin. This represents a major step towards trapping the anti-atom, thus opening a new avenue into the investigation of antimatter properties.   Members of the ALPHA collaboration working on the apparatus in the Antiproton Decelerator experimental hall at CERN. Just like the atom, the anti-atom is neutral. Unlike the atom, the anti-atom is made up of antiprotons (as opposed to protons in the atom) and positrons (as opposed to electrons). In order to thoroughly study the properties of the anti-atoms, scien...

  10. Assessing record linkage between health care and Vital Statistics databases using deterministic methods

    OpenAIRE

    Quan Hude; Li Bing; Fong Andrew; Lu Mingshan

    2006-01-01

    Abstract Background We assessed the linkage and correct linkage rate using deterministic record linkage among three commonly used Canadian databases, namely, the population registry, hospital discharge data and Vital Statistics registry. Methods Three combinations of four personal identifiers (surname, first name, sex and date of birth) were used to determine the optimal combination. The correct linkage rate was assessed using a unique personal health number available in all three databases. ...

  11. Data and animal management software for large-scale phenotype screening.

    Science.gov (United States)

    Ching, Keith A; Cooke, Michael P; Tarantino, Lisa M; Lapp, Hilmar

    2006-04-01

    The mouse N-ethyl-N-nitrosourea (ENU) mutagenesis program at the Genomics Institute of the Novartis Research Foundation (GNF) uses MouseTRACS to analyze phenotype screens and manage animal husbandry. MouseTRACS is a Web-based laboratory informatics system that electronically records and organizes mouse colony operations, prints cage cards, tracks inventory, manages requests, and reports Institutional Animal Care and Use Committee (IACUC) protocol usage. For efficient phenotype screening, MouseTRACS identifies mutants, visualizes data, and maps mutations. It displays and integrates phenotype and genotype data using likelihood odds ratio (LOD) plots of genetic linkage between genotype and phenotype. More detailed mapping intervals show individual single nucleotide polymorphism (SNP) markers in the context of phenotype. In addition, dynamically generated pedigree diagrams and inventory reports linked to screening results summarize the inheritance pattern and the degree of penetrance. MouseTRACS displays screening data in tables and uses standard charts such as box plots, histograms, scatter plots, and customized charts looking at clustered mice or cross pedigree comparisons. In summary, MouseTRACS enables the efficient screening, analysis, and management of thousands of animals to find mutant mice and identify novel gene functions. MouseTRACS is available under an open source license at http://www.mousetracs.sourceforge.net. PMID:16596450

  12. Data and animal management software for large-scale phenotype screening.

    Science.gov (United States)

    Ching, Keith A; Cooke, Michael P; Tarantino, Lisa M; Lapp, Hilmar

    2006-04-01

    The mouse N-ethyl-N-nitrosourea (ENU) mutagenesis program at the Genomics Institute of the Novartis Research Foundation (GNF) uses MouseTRACS to analyze phenotype screens and manage animal husbandry. MouseTRACS is a Web-based laboratory informatics system that electronically records and organizes mouse colony operations, prints cage cards, tracks inventory, manages requests, and reports Institutional Animal Care and Use Committee (IACUC) protocol usage. For efficient phenotype screening, MouseTRACS identifies mutants, visualizes data, and maps mutations. It displays and integrates phenotype and genotype data using likelihood odds ratio (LOD) plots of genetic linkage between genotype and phenotype. More detailed mapping intervals show individual single nucleotide polymorphism (SNP) markers in the context of phenotype. In addition, dynamically generated pedigree diagrams and inventory reports linked to screening results summarize the inheritance pattern and the degree of penetrance. MouseTRACS displays screening data in tables and uses standard charts such as box plots, histograms, scatter plots, and customized charts looking at clustered mice or cross pedigree comparisons. In summary, MouseTRACS enables the efficient screening, analysis, and management of thousands of animals to find mutant mice and identify novel gene functions. MouseTRACS is available under an open source license at http://www.mousetracs.sourceforge.net.

  13. Partitioning $\\alpha$-large sets for $\\alpha<\\varepsilon_{\\omega}$

    CERN Document Server

    De Smet, Michiel

    2010-01-01

    We generalise the results by Bigorajska and Kotlarski about partitioning $\\alpha$-large sets, by extending the domain up to ordinals below $\\varepsilon_{\\omega}$. These results will be very useful to give a miniaturisation of the infinite Ramsey Theorem.

  14. Synthesis of a precursor for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha,17 beta-diol 17-glucuronide

    International Nuclear Information System (INIS)

    Starting from 11 beta-hydroxytestosterone, the synthesis of a strategic precursor, C-9 (11) unsaturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide (9a), for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide has been achieved. The authors optimized the reaction conditions for catalytic reduction employing hydrogen and subsequent base hydrolysis followed by purification on Amberlite XAD-2 resin to obtain the saturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide

  15. The molecular genetic linkage map of the model legume Medicago truncatula: an essential tool for comparative legume genomics and the isolation of agronomically important genes

    Directory of Open Access Journals (Sweden)

    Ané Jean-Michel

    2002-01-01

    Full Text Available Abstract Background The legume Medicago truncatula has emerged as a model plant for the molecular and genetic dissection of various plant processes involved in rhizobial, mycorrhizal and pathogenic plant-microbe interactions. Aiming to develop essential tools for such genetic approaches, we have established the first genetic map of this species. Two parental homozygous lines were selected from the cultivar Jemalong and from the Algerian natural population (DZA315 on the basis of their molecular and phenotypic polymorphism. Results An F2 segregating population of 124 individuals between these two lines was obtained using an efficient manual crossing technique established for M. truncatula and was used to construct a genetic map. This map spans 1225 cM (average 470 kb/cM and comprises 289 markers including RAPD, AFLP, known genes and isoenzymes arranged in 8 linkage groups (2n = 16. Markers are uniformly distributed throughout the map and segregation distortion is limited to only 3 linkage groups. By mapping a number of common markers, the eight linkage groups are shown to be homologous to those of diploid alfalfa (M. sativa, implying a good level of macrosynteny between the two genomes. Using this M. truncatula map and the derived F3 populations, we were able to map the Mtsym6 symbiotic gene on linkage group 8 and the SPC gene, responsible for the direction of pod coiling, on linkage group 7. Conclusions These results demonstrate that Medicago truncatula is amenable to diploid genetic analysis and they open the way to map-based cloning of symbiotic or other agronomically-important genes using this model plant.

  16. A genetic linkage map for the saltwater crocodile (Crocodylus porosus

    Directory of Open Access Journals (Sweden)

    Lance Stacey L

    2009-07-01

    Full Text Available Abstract Background Genome elucidation is now in high gear for many organisms, and whilst genetic maps have been developed for a broad array of species, surprisingly, no such maps exist for a crocodilian, or indeed any other non-avian member of the Class Reptilia. Genetic linkage maps are essential tools for the mapping and dissection of complex quantitative trait loci (QTL, and in order to permit systematic genome scans for the identification of genes affecting economically important traits in farmed crocodilians, a comprehensive genetic linage map will be necessary. Results A first-generation genetic linkage map for the saltwater crocodile (Crocodylus porosus was constructed using 203 microsatellite markers amplified across a two-generation pedigree comprising ten full-sib families from a commercial population at Darwin Crocodile Farm, Northern Territory, Australia. Linkage analyses identified fourteen linkage groups comprising a total of 180 loci, with 23 loci remaining unlinked. Markers were ordered within linkage groups employing a heuristic approach using CRIMAP v3.0 software. The estimated female and male recombination map lengths were 1824.1 and 319.0 centimorgans (cM respectively, revealing an uncommonly large disparity in recombination map lengths between sexes (ratio of 5.7:1. Conclusion We have generated the first genetic linkage map for a crocodilian, or indeed any other non-avian reptile. The uncommonly large disparity in recombination map lengths confirms previous preliminary evidence of major differences in sex-specific recombination rates in a species that exhibits temperature-dependent sex determination (TSD. However, at this point the reason for this disparity in saltwater crocodiles remains unclear. This map will be a valuable resource for crocodilian researchers, facilitating the systematic genome scans necessary for identifying genes affecting complex traits of economic importance in the crocodile industry. In addition

  17. The first linkage map of the American mink (Mustela vison)

    DEFF Research Database (Denmark)

    Anistoroaei, Razvan Marian; Menzorov, A.; Serov, O.;

    2007-01-01

    Described herein, the first microsatellite linkage map for the American mink consists of 85 microsatellite markers resolved into 17 linkage groups. The map was constructed using 92 F1 progeny from five sire families created by crossing mink with different colour types. The linkage groups ranged f...

  18. Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia.

    Science.gov (United States)

    Weiss, Mitchell J; Zhou, Suiping; Feng, Liang; Gell, David A; Mackay, Joel P; Shi, Yigong; Gow, Andrew J

    2005-01-01

    Hemoglobin (Hb) synthesis is coordinated by homeostatic mechanisms to limit the accumulation of free alpha or beta subunits, which are cytotoxic. Alpha hemoglobin-stabilizing protein (AHSP) is an abundant erythroid protein that specifically binds free alphaHb, stabilizes its structure, and limits its ability to participate in chemical reactions that generate reactive oxygen species. Gene ablation studies in mice demonstrate that AHSP is required for normal erythropoiesis. AHSP-null erythrocytes are short-lived, contain Hb precipitates, and exhibit signs of oxidative damage. Loss of AHSP exacerbates beta-thalassemia in mice, indicating that altered AHSP expression or function could modify thalassemia phenotypes in humans, a topic that is beginning to be explored in clinical studies. We used biochemical, spectroscopic, and crystallographic methods to examine how AHSP stabilizes alphaHb. AHSP binds the G and H helices of alphaHb on a surface that largely overlaps with the alpha1-beta1 interface of HbA. This result explains previous findings that betaHb can competitively displace AHSP from alphaHb to form HbA tetramer. Remarkably, binding of AHSP to oxygenated alphaHb induces dramatic conformational changes and converts the heme-bound iron to an oxidized hemichrome state in which all six coordinate positions are occupied. This structure limits the reactivity of heme iron, providing a mechanism by which AHSP stabilizes alphaHb. These findings suggest a biochemical pathway through which AHSP might participate in normal Hb synthesis and modulate the severity of thalassemias. Moreover, understanding how AHSP stabilizes alphaHb provides a theoretical basis for new strategies to inhibit the damaging effects of free alphaHb that accumulates in beta-thalassemia.

  19. Construction and comparative analyses of highly dense linkage maps of two sweet cherry intra-specific progenies of commercial cultivars.

    Directory of Open Access Journals (Sweden)

    Carolina Klagges

    Full Text Available Despite the agronomical importance and high synteny with other Prunus species, breeding improvements for cherry have been slow compared to other temperate fruits, such as apple or peach. However, the recent release of the peach genome v1.0 by the International Peach Genome Initiative and the sequencing of cherry accessions to identify Single Nucleotide Polymorphisms (SNPs provide an excellent basis for the advancement of cherry genetic and genomic studies. The availability of dense genetic linkage maps in phenotyped segregating progenies would be a valuable tool for breeders and geneticists. Using two sweet cherry (Prunus avium L. intra-specific progenies derived from crosses between 'Black Tartarian' × 'Kordia' (BT×K and 'Regina' × 'Lapins'(R×L, high-density genetic maps of the four parental lines and the two segregating populations were constructed. For BT×K and R×L, 89 and 121 F(1 plants were used for linkage mapping, respectively. A total of 5,696 SNP markers were tested in each progeny. As a result of these analyses, 723 and 687 markers were mapped into eight linkage groups (LGs in BT×K and R×L, respectively. The resulting maps spanned 752.9 and 639.9 cM with an average distance of 1.1 and 0.9 cM between adjacent markers in BT×K and R×L, respectively. The maps displayed high synteny and co-linearity between each other, with the Prunus bin map, and with the peach genome v1.0 for all eight LGs (LG1-LG8. These maps provide a useful tool for investigating traits of interest in sweet cherry and represent a qualitative advance in the understanding of the cherry genome and its synteny with other members of the Rosaceae family.

  20. Construction and comparative analyses of highly dense linkage maps of two sweet cherry intra-specific progenies of commercial cultivars.

    Science.gov (United States)

    Klagges, Carolina; Campoy, José Antonio; Quero-García, José; Guzmán, Alejandra; Mansur, Levi; Gratacós, Eduardo; Silva, Herman; Rosyara, Umesh R; Iezzoni, Amy; Meisel, Lee A; Dirlewanger, Elisabeth

    2013-01-01

    Despite the agronomical importance and high synteny with other Prunus species, breeding improvements for cherry have been slow compared to other temperate fruits, such as apple or peach. However, the recent release of the peach genome v1.0 by the International Peach Genome Initiative and the sequencing of cherry accessions to identify Single Nucleotide Polymorphisms (SNPs) provide an excellent basis for the advancement of cherry genetic and genomic studies. The availability of dense genetic linkage maps in phenotyped segregating progenies would be a valuable tool for breeders and geneticists. Using two sweet cherry (Prunus avium L.) intra-specific progenies derived from crosses between 'Black Tartarian' × 'Kordia' (BT×K) and 'Regina' × 'Lapins'(R×L), high-density genetic maps of the four parental lines and the two segregating populations were constructed. For BT×K and R×L, 89 and 121 F(1) plants were used for linkage mapping, respectively. A total of 5,696 SNP markers were tested in each progeny. As a result of these analyses, 723 and 687 markers were mapped into eight linkage groups (LGs) in BT×K and R×L, respectively. The resulting maps spanned 752.9 and 639.9 cM with an average distance of 1.1 and 0.9 cM between adjacent markers in BT×K and R×L, respectively. The maps displayed high synteny and co-linearity between each other, with the Prunus bin map, and with the peach genome v1.0 for all eight LGs (LG1-LG8). These maps provide a useful tool for investigating traits of interest in sweet cherry and represent a qualitative advance in the understanding of the cherry genome and its synteny with other members of the Rosaceae family. PMID:23382953

  1. High-resolution gene mapping using admixture linkage disequilibrium

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    This note reports simulation study on the rate of decay in linkage dis equilibrium (LD) in mixed populations over multiple discrete generations and explores the usefulness of the LD analysis in high-resolution gene mapping. The results indicate that the smaller the recombination fraction and the fewer generati ons since admixtureevent, the higher power of the approach in gene mapping. The expected estimate of recombination fraction would give an estimate that is slig htly biased upwards, if relevant genes are in tight linkage. The estimated recom bination fraction is usually larger than the true value within 2-5 generations. From generations 10-20, the mean estimates are in good agreement with the true value. The method presented here enables estimation of means and corresponding confidence intervals of the recombination fraction at any number of generations.

  2. Linkage analysis on chromosome 2 in essential hypotension pedigrees

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It is a new approach to study the important genes related to the control of blood pressure by probing into hypotension and hypertension at the same time. Genome scanning on whole chromosome 2 in 8 hypotension pedigrees has been done and parameter (LOD score) and non-pa- rameter (NPL score) were used in the linkage analysis by GENEHUNTER software. The results show the evidence of linkage between D2S112 and D2S117, indicating a number of critical genes may lie in thisregion and contribute to the mechanism of blood pressure regulation. Also this region has been found in the previous study in hypertension pedigrees. These genes may play an important role in the regulation of blood pressure and can also be the important candidate genes in hypertension studies.

  3. An improved recommendation algorithm via weakening indirect linkage effect

    Science.gov (United States)

    Chen, Guang; Qiu, Tian; Shen, Xiao-Quan

    2015-07-01

    We propose an indirect-link-weakened mass diffusion method (IMD), by considering the indirect linkage and the source object heterogeneity effect in the mass diffusion (MD) recommendation method. Experimental results on the MovieLens, Netflix, and RYM datasets show that, the IMD method greatly improves both the recommendation accuracy and diversity, compared with a heterogeneity-weakened MD method (HMD), which only considers the source object heterogeneity. Moreover, the recommendation accuracy of the cold objects is also better elevated in the IMD than the HMD method. It suggests that eliminating the redundancy induced by the indirect linkages could have a prominent effect on the recommendation efficiency in the MD method. Project supported by the National Natural Science Foundation of China (Grant No. 11175079) and the Young Scientist Training Project of Jiangxi Province, China (Grant No. 20133BCB23017).

  4. Alpha thalassaemia in British people.

    OpenAIRE

    Higgs, D R; Ayyub, H.; Clegg, J B; Hill, A V; Nicholls, R D; Teal, H; Wainscoat, J.S. (James S.); Weatherall, D. J.

    1985-01-01

    Although alpha thalassaemia is rare in north Europeans, it has been identified in British people with no known foreign ancestry. Twelve such patients were studied, of whom eight shared a distinctive molecular defect, which was clearly different from defects seen in subjects of Mediterranean or South East Asian origin. A rare but specific form of alpha thalassaemia is therefore present in the British population. In addition, two patients from families of mixed racial origin were encountered wh...

  5. Deciphering the Galaxy Guppy phenotype

    Directory of Open Access Journals (Sweden)

    Philip Shaddock

    2011-01-01

    Full Text Available Animal breeding hobbyists have been useful to science because they identify and isolate colorcoat mutations that geneticists can in turn use in their studies of the development and differentiation ofcolor cells. This paper discusses a very interesting color mutant, the Japanese Galaxy, tracing its creationfrom back to a self-educated genetics hobbyist, Hoskiki Tsutsui. The paper discusses a constituent genepreviously studied by Dr. Violet Phang, the snakeskin gene (the linked body and fin genes Ssb and Sst.And it discusses a gene previously unknown to science, the Schimmelpfennig Platinum gene (Sc.Through crossing experiments, the author determines that the combination of these two genes producesan intermediate phenotype, the Medusa. Incorporating the Grass (Gr, another gene unknown to sciencegene into the Medusa through a crossover produces the Galaxy phenotype. Microscope studies of thesnakeskin pattern in Galaxies and snakeskins reveals some parallels with similar studies made of theZebrafish Danio.

  6. Almost Redundant Components in the 3 alpha Faddeev Equation for the Buck, Friedlich and Wheatly alpha alpha Potential

    CERN Document Server

    Fujiwara, Y; Kohno, M

    2004-01-01

    The 3 alpha orthogonality condition model using the Pauli-forbidden bound states of the Buck, Friedlich and Wheatly alpha alpha potential can yield a compact 3 alpha ground state with a large binding energy, in which a small admixture of the redundant components can never be eliminated.

  7. Primary structure determination of five sialylated oligosaccharides derived from bronchial mucus glycoproteins of patients suffering from cystic fibrosis. The occurrence of the NeuAc alpha(2----3)Gal beta(1----4)[Fuc alpha(1----3)] GlcNAc beta(1----.) structural element revealed by 500-MHz 1H NMR spectroscopy.

    Science.gov (United States)

    Lamblin, G; Boersma, A; Klein, A; Roussel, P; van Halbeek, H; Vliegenthart, J F

    1984-07-25

    The structure of sialylated carbohydrate units of bronchial mucins obtained from cystic fibrosis patients was investigated by 500-MHz 1H NMR spectroscopy in conjunction with sugar analysis. After subjecting the mucins to alkaline borohydride degradation, sialylated oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by high performance liquid chromatography. Five compounds could be obtained in a rather pure state; their structures were established as the following: A-1, NeuAc alpha(2----3)Gal beta(1----4) [Fuc alpha(1----3)]GlcNAc beta(1----3)Gal-NAc-ol; A-2, NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)-[GlcNAc beta (1----3)]GalNAc-o1; A-3, NeuAc alpha(2----3)Gal beta-(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----3)Gal beta(1----3) GalNAc-o1; A-4, NeuAc alpha(2----3)Gal beta(1----4)[Fuc alpha(1----3)]Glc-NAc NAc beta(1----6)[GlcNAc beta(1----3)]GalNAc-o1; A-6,NeuAc alpha-(2----3) Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----6)[Gal beta-(1----4) GlcNAc beta(1----3)]GalNAc-o1. The simultaneous presence of sialic acid in alpha(2----3)-linkage to Gal and fucose in alpha(1----3)-linkage to GlcNAc of the same N-acetyllactosamine unit could be adequately proved by high resolution 1H NMR spectroscopy. This sequence constitutes a novel structural element for mucins.

  8. Primary structure determination of five sialylated oligosaccharides derived from bronchial mucus glycoproteins of patients suffering from cystic fibrosis. The occurrence of the NeuAc alpha(2----3)Gal beta(1----4)[Fuc alpha(1----3)] GlcNAc beta(1----.) structural element revealed by 500-MHz 1H NMR spectroscopy.

    Science.gov (United States)

    Lamblin, G; Boersma, A; Klein, A; Roussel, P; van Halbeek, H; Vliegenthart, J F

    1984-07-25

    The structure of sialylated carbohydrate units of bronchial mucins obtained from cystic fibrosis patients was investigated by 500-MHz 1H NMR spectroscopy in conjunction with sugar analysis. After subjecting the mucins to alkaline borohydride degradation, sialylated oligosaccharide-alditols were isolated by anion-exchange chromatography and fractionated by high performance liquid chromatography. Five compounds could be obtained in a rather pure state; their structures were established as the following: A-1, NeuAc alpha(2----3)Gal beta(1----4) [Fuc alpha(1----3)]GlcNAc beta(1----3)Gal-NAc-ol; A-2, NeuAc alpha(2----3)Gal beta(1----4)GlcNAc beta(1----6)-[GlcNAc beta (1----3)]GalNAc-o1; A-3, NeuAc alpha(2----3)Gal beta-(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----3)Gal beta(1----3) GalNAc-o1; A-4, NeuAc alpha(2----3)Gal beta(1----4)[Fuc alpha(1----3)]Glc-NAc NAc beta(1----6)[GlcNAc beta(1----3)]GalNAc-o1; A-6,NeuAc alpha-(2----3) Gal beta(1----4)[Fuc alpha(1----3)]GlcNAc beta(1----6)[Gal beta-(1----4) GlcNAc beta(1----3)]GalNAc-o1. The simultaneous presence of sialic acid in alpha(2----3)-linkage to Gal and fucose in alpha(1----3)-linkage to GlcNAc of the same N-acetyllactosamine unit could be adequately proved by high resolution 1H NMR spectroscopy. This sequence constitutes a novel structural element for mucins. PMID:6746638

  9. MITOCHONDRIAL HAPLOGROUPS DEFINE TWO PHENOTYPES OF OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    Mercedes eFernandez-Moreno

    2012-05-01

    Full Text Available Objective. To assess a mitochondrion-related phenotype in patients with osteoarthritis (OA.Methods. Serum levels of the following OA-related biomarkers: matrix metalloproteinase-1 (MMP-1; MMP-3; MMP-13; myeloperoxidase (MPO; a peptide of the alpha-helical region of type II collagen, Coll2-1, and its nitrated form Coll2-1NO2; a C-terminal neoepitope generated by the collagenase-mediated cleavage of collagen type II triple helix, C2C; the C-propeptide of collagen type II, CPII; hyaluronic acid (HA; human cartilage glycoprotein-39, YKL-40; cartilage oligomeric matrix protein (COMP and cathepsin K were analyzed in 48 OA patients and 52 healthy controls carrying the haplogroups H and J. Logistic regression models and Receiver Operating Characteristic (ROC curves were performed to predict the onset of OA. Results. MMP-13 was the only biomarker significantly increased in OA patients compared to healthy controls in both haplogroups H and J. The collagen type II biomarkers, Coll2-1, Coll2-1NO2, the Coll2-1NO2/Coll2-1 ratio, C2C, CPII and the C2C:CPII ratio were significantly increased in OA patients carrying haplogroup H compared to OA carriers of the haplogroup J. Two logistic regression models for diagnosis were constructed and adjusted for age, gender and body mass index (BMI. For haplogroup H, the biomarkers significantly associated with OA were MMP-13 and Coll2-1; the area under the curve (AUC of the ROC curve for this model was 0.952 (95%CI=0.892-1.012. For haplogroup J, the only biomarker significantly associated with OA was MMP-13; the AUC for this model was 0.895 (95%CI=0.801-0.989.Conclusion. Some OA-related biomarkers show a clearly different profile depending on the mtDNA haplogroup.

  10. Multimarket linkages, buyer power, and the productivity puzzle

    OpenAIRE

    Matsushima, Noriaki; Zhao, Laixun

    2010-01-01

    This paper examines the relationship between firms' productivity improvement and the volume of exports, and shows that it can be sometimes negative. Specifically, we simultaneously take into account intermediate retailers (i.e., vertically) and multimarket linkages (i.e., horizontally). We find that an improvement of the manufacturing productivity affects the bargained wholesale prices in opposite directions in asymmetric markets, causing retailers to make corresponding changes that look surp...

  11. Agricultural growth linkages in Sub-Saharan Africa

    OpenAIRE

    Delgado, C.L.; J. Hopkins; Kelly, V.A.; Hazell, P.; McKenna, A.A.; Gruhn, P.; Hojjati, B.; Sil, J.; Courbois, C.

    1998-01-01

    After reviewing the literature on agricultural growth linkages in Africa, this report examines the mix of farm and non-farm goods and services that rural Africans purchase, and the implications of these expenditures for rural economic growth in five African countries: Burkina Faso, Niger, Senegal, Zambia, and Zimbabwe. In the West African countries, in addition to farm and non-farm sectors, individual commodities are sorted into tradable and non-tradable categories, and by geographic zones of...

  12. Farm production diversity and dietary quality: Linkages and measurement issues

    OpenAIRE

    Sibhatu, Kibrom T.; Qaim, Matin

    2016-01-01

    Recent research has analyzed whether higher levels of farm production diversity contribute to improved dietary quality in smallholder households. We add to this literature by using different indicators, thus testing the robustness of previous findings and helping to better understand the underlying linkages. The analysis builds on data from Indonesia, Kenya, and Uganda. Farm diversity measured through a simple species count has a small positive effect on dietary quality, either expressed in t...

  13. Linear models for joint association and linkage QTL mapping

    Directory of Open Access Journals (Sweden)

    Fernando Rohan L

    2009-09-01

    Full Text Available Abstract Background Populational linkage disequilibrium and within-family linkage are commonly used for QTL mapping and marker assisted selection. The combination of both results in more robust and accurate locations of the QTL, but models proposed so far have been either single marker, complex in practice or well fit to a particular family structure. Results We herein present linear model theory to come up with additive effects of the QTL alleles in any member of a general pedigree, conditional to observed markers and pedigree, accounting for possible linkage disequilibrium among QTLs and markers. The model is based on association analysis in the founders; further, the additive effect of the QTLs transmitted to the descendants is a weighted (by the probabilities of transmission average of the substitution effects of founders' haplotypes. The model allows for non-complete linkage disequilibrium QTL-markers in the founders. Two submodels are presented: a simple and easy to implement Haley-Knott type regression for half-sib families, and a general mixed (variance component model for general pedigrees. The model can use information from all markers. The performance of the regression method is compared by simulation with a more complex IBD method by Meuwissen and Goddard. Numerical examples are provided. Conclusion The linear model theory provides a useful framework for QTL mapping with dense marker maps. Results show similar accuracies but a bias of the IBD method towards the center of the region. Computations for the linear regression model are extremely simple, in contrast with IBD methods. Extensions of the model to genomic selection and multi-QTL mapping are straightforward.

  14. Linkages Over Time Between Adolescents' Relationships with Parents and Friends

    OpenAIRE

    De Goede, Irene H. A.; Branje, Susan J. T.; Delsing, Marc J. M. H.; Meeus, Wim H. J.

    2009-01-01

    This 5-wave longitudinal study examines linkages over time between adolescents’ perceptions of relationships with parents and friends with respect to support, negative interaction, and power. A total of 575 early adolescents (54.1% boys) and 337 middle adolescents (43.3% boys) participated. Path analyses mainly showed bidirectional associations between adolescents’ perceptions of parent–adolescent relationships and friendships with a predominantly stronger influence from parent–adolescent rel...

  15. Paroxysmal dystonic choreoathetosis: tight linkage to chromosome 2q.

    OpenAIRE

    Fink, J K; Rainer, S.; Wilkowski, J.; Jones, S. M.; Kume, A.; Hedera, P; Albin, R.; Mathay, J.; Girbach, L.; Varvil, T; Otterud, B; Leppert, M

    1996-01-01

    Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosom...

  16. Modeling nonlinear and heterogeneous dynamic linkages in international monetary markets

    OpenAIRE

    Mohamed El Hedi Arouri; Fredj Jawadi; Khuong Nguyen Duc

    2010-01-01

    In this paper we examine the dynamic linkages of international monetary markets over the 2004 - 2009 period using daily short-term interbank interest rates of three of the most advanced countries (France, United Kingdom and United States). Empirical results from vector error-correction models (VECM) and smooth transition error-correction models (STECM) indicate strong evidence of nonlinear and heterogeneous causalities between the three interest rates considered. We also find that exogenous s...

  17. Genome scan for linkage to Gilles de la Tourette syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Barr, C.L.; Livingston, J.; Williamson, R. [and others

    1994-09-01

    Gilles de la Tourette Syndrome (TS) is a familial, neuropsychiatric disorder characterized by chronic, intermittent motor and vocal tics. In addition to tics, affected individuals frequently display symptoms such as attention-deficit hyperactivity disorder and/or obsessive compulsive disorder. Genetic analyses of family data have suggested that susceptibility to the disorder is most likely due to a single genetic locus with a dominant mode of transmission and reduced penetrance. In the search for genetic linkage for TS, we have collected well-characterized pedigrees with multiple affected individuals on whom extensive diagnostic evaluations have been done. The first stage of our study is to scan the genome systematically using a panel of uniformly spaced (10 to 20 cM), highly polymorphic, microsatellite markers on 5 families segregating TS. To date, 290 markers have been typed and 3,660 non-overlapping cM of the genome have been excluded for possible linkage under the assumption of genetic homogeneity. Because of the possibility of locus heterogeneity overall summed exclusion is not considered tantamount to absolute exclusion of a disease locus in that region. The results from each family are carefully evaluated and a positive lod score in a single family is followed up by typing closely linked markers. Linkage to TS was examined by two-point analysis using the following genetic model: single autosomal dominant gene with gene frequency .003 and maximum penetrance of .99. An age-of-onset correction is included using a linear function increasing from age 2 years to 21 years. A small rate of phenocopies is also incorporated into the model. Only individuals with TS or CMT according to DSM III-R criteria were regarded as affected for the purposes of this summary. Additional markers are being tested to provide coverage at 5 cM intervals. Moreover, we are currently analyzing the data non-parametrically using the Affected-Pedigree-Member Method of linkage analysis.

  18. Linkage between productivity and innovation in different service sectors

    OpenAIRE

    Rõigas, Kärt

    2011-01-01

    The purpose of the paper is to find out whether linkages between productivity and innovation are different among Estonian service sector sub-sectors. In this paper productivity is measured as value added per employee. An original approach toward measurement of productivity is used, decomposing it into three components: labour costs, depreciation and gross profit per employee. Four types of innovation are studied: product, process, organizational and marketing innovation. The empirical analysi...

  19. Genetic by environment interactions affect plant–soil linkages

    OpenAIRE

    Pregitzer, Clara C; Joseph K Bailey; Schweitzer, Jennifer A.

    2013-01-01

    The role of plant intraspecific variation in plant–soil linkages is poorly understood, especially in the context of natural environmental variation, but has important implications in evolutionary ecology. We utilized three 18- to 21-year-old common gardens across an elevational gradient, planted with replicates of five Populus angustifolia genotypes each, to address the hypothesis that tree genotype (G), environment (E), and G × E interactions would affect soil carbon and nitrogen dynamics be...

  20. Formal-informal economy linkages and unemployment in South Africa:

    OpenAIRE

    Davies, Rob; Thurlow, James

    2009-01-01

    South Africa's high involuntary unemployment and small informal sector are attributed to an underperforming formal sector and barriers to entry in the informal sector. This paper examines the economywide linkages between the formal and informal economies while accounting for different types of informal activities. A multiregion empirically calibrated general equilibrium model is developed capturing both product and labor markets. Three policy options are considered. First, results indicate th...

  1. Phenotypic expression in mucopolysaccharidosis VII.

    OpenAIRE

    Bernsen, P L; Wevers, R. A.; Gabreëls, F J; Lamers, K J; Sonnen, A E; Stekhoven, J H

    1987-01-01

    beta-glucuronidase deficiency is an extremely rare disorder which is known to have a considerable phenotypic variation. A survey of the clinical findings in 19 previously reported patients with mucopolysaccharidosis VII is presented together with the results of clinical and biochemical studies in two further patients. Because a similar clinical picture is present in a heterozygotic sister it is doubted whether all signs and symptoms can be attributed to the beta-glucuronidase deficiency. The ...

  2. Statistical models for trisomic phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Lamb, N.E.; Sherman, S.L.; Feingold, E. [Emory Univ., Atlanta, GA (United States)

    1996-01-01

    Certain genetic disorders are rare in the general population but more common in individuals with specific trisomies, which suggests that the genes involved in the etiology of these disorders may be located on the trisomic chromosome. As with all aneuploid syndromes, however, a considerable degree of variation exists within each phenotype so that any given trait is present only among a subset of the trisomic population. We have previously presented a simple gene-dosage model to explain this phenotypic variation and developed a strategy to map genes for such traits. The mapping strategy does not depend on the simple model but works in theory under any model that predicts that affected individuals have an increased likelihood of disomic homozygosity at the trait locus. This paper explores the robustness of our mapping method by investigating what kinds of models give an expected increase in disomic homozygosity. We describe a number of basic statistical models for trisomic phenotypes. Some of these are logical extensions of standard models for disomic phenotypes, and some are more specific to trisomy. Where possible, we discuss genetic mechanisms applicable to each model. We investigate which models and which parameter values give an expected increase in disomic homozygosity in individuals with the trait. Finally, we determine the sample sizes required to identify the increased disomic homozygosity under each model. Most of the models we explore yield detectable increases in disomic homozygosity for some reasonable range of parameter values, usually corresponding to smaller trait frequencies. It therefore appears that our mapping method should be effective for a wide variety of moderately infrequent traits, even though the exact mode of inheritance is unlikely to be known. 21 refs., 8 figs., 1 tab.

  3. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  4. [Plasticity of the cellular phenotype].

    Science.gov (United States)

    Chneiweiss, Hervé

    2011-01-01

    The tragical consequences of the Hiroshima and Nagasaki atomic bombs in 1945 were to lead to the discovery of hematopoietic stem cells and their phenotypic plasticity, in response to environmental factors. These concepts were much later extended to the founding cells of other tissues. In the following collection of articles, the mechanisms underlying this plasticity, at the frontiers of developmental biology and oncology, are illustrated in the case of various cell types of neural origin and of some tumours. PMID:21501574

  5. Construction of a genetic linkage map and QTL analysis for some leaf traits in pear (Pyrus L .)

    Institute of Scientific and Technical Information of China (English)

    Wenying SUN; Yuxing ZHANG; Wenquan LE; Hai'e ZHANG

    2009-01-01

    The major incompatibility barriers to specific inbred lines and the long generation duration in Pyrus L. May hinder the Pyrus breeding process. A genetic linkage map provides the foundation for quantitative trait loci (QTL) mapping and molecular marker-assisted breeding. In this study, we constructed a genetic map with 145 F1 populations from a cross of two cultivars, Yali and Jingbaili, using AFLP and SSR markers. The map consisted of 18 linkage groups which included 402 genetic markers and covered 1395.9 cM, with an average genetic distance of 3.8 cM. The interval mapping was used to identify quantitative trait loci associated with four leaf agronomic traits in the F1 population. The results indicated that four QTLs were associated with leaf length, two QTLs with leaf width, two with leaf length/leaf width, and three with petiole length. The eleven QTLs were associated with 9.9%-48.5% of the phenotypic variation in different traits. It is considered that the map covers almost the whole genome, and molecular markers will be greatly helpful to the related breeding.

  6. Bacterial zoonoses of fishes: a review and appraisal of evidence for linkages between fish and human infections.

    Science.gov (United States)

    Gauthier, David T

    2015-01-01

    Human contact with and consumption of fishes presents hazards from a range of bacterial zoonotic infections. Whereas many bacterial pathogens have been presented as fish-borne zoonoses on the basis of epidemiological and phenotypic evidence, genetic identity between fish and human isolates is not frequently examined or does not provide support for transmission between these hosts. In order to accurately assess the zoonotic risk from exposure to fishes in the context of aquaculture, wild fisheries and ornamental aquaria, it is important to critically examine evidence of linkages between bacteria infecting fishes and humans. This article reviews bacteria typically presented as fish-borne zoonoses, and examines the current strength of evidence for this classification. Of bacteria generally described as fish-borne zoonoses, only Mycobacterium spp., Streptococcus iniae, Clostridium botulinum, and Vibrio vulnificus appear to be well-supported as zoonoses in the strict sense. Erysipelothrix rhusiopathiae, while transmissible from fishes to humans, does not cause disease in fishes and is therefore excluded from the list. Some epidemiological and/or molecular linkages have been made between other bacteria infecting both fishes and humans, but more work is needed to elucidate routes of transmission and the identity of these pathogens in their respective hosts at the genomic level. PMID:25466575

  7. Genetic background of phenotypic variation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A noteworthy feature of the living world is its bewildering variability. A key issue in several biological disciplines is the achievement of an understanding of the hereditary basis of this variability. Two opposing, but not necessarily irreconcilable conceptions attempt to explain the underlying mechanism. The gene function paradigm postulates that phenotypic variance is generated by the polymorphism in the coding sequences of genes. However, comparisons of a great number of homologous gene and protein sequences have revealed that they predominantly remained functionally conserved even across distantly related phylogenic taxa. Alternatively, the gene regulation paradigm assumes that differences in the cis-regulatory region of genes do account for phenotype variation within species. An extension of this latter concept is that phenotypic variability is generated by the polyrnorphism in the overall gene expression profiles of gene networks.In other words, the activity of a particular gene is a system property determined both by the cis-regulatory sequences of the given genes and by the other genes of a gene network, whose expressions vary among individuals, too. Novel proponents of gene function paradigm claim that functional genetic variance within the coding sequences of regulatory genes is critical for the generation of morphological polymorphism. Note, however, that these developmental genes play direct regulatory roles in the control of gene expression.

  8. Adaptive evolution of molecular phenotypes

    Science.gov (United States)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-09-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak.

  9. A three-tier phenotyping approach for hunting QTLs related to heat tolerance in bread wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari; Rosenqvist, Eva; Ottosen, Carl-Otto;

    functionality, therefore, its physiological relevance in terms of overall plant performance was validated under moderate heat stress (36°C for a week) mimicking natural heat waves. Interestingly, the wheat cultivars previously selected for high Fv/Fm also showed higher net photosynthesis,chlorophyll content......, wheat is sensitive to heat stress, particularly at the reproductive phase. Heat tolerance is a complex trait. In the present study, a combined approach of physiological phenotyping and quantitative genetics was used to dissect the complex nature of heat tolerance into photosynthesis related traits......: Genotyping and linkage analysis of molecular markers was carried out to analyze quantitative trait loci (QTLs) in three bi-parental segregating populations derived from the parents contrasting for Fv/Fm. Three QTLs each explaining about 12-16% of the phenotypic variation were mapped at a resolution of around...

  10. Pedimap: software for the visualization of genetic and phenotypic data in pedigrees.

    Science.gov (United States)

    Voorrips, Roeland E; Bink, Marco C A M; van de Weg, W Eric

    2012-01-01

    Pedimap is a user-friendly software tool for visualizing phenotypic and genotypic data for related individuals linked in pedigrees. Genetic data can include marker scores, Identity-by-Descent probabilities, and marker linkage map positions, allowing the visualization of haplotypes through lineages. The pedigrees can accommodate all types of inheritance, including selfing, cloning, and repeated backcrossing, and all ploidy levels are supported. Visual association of the genetic data with phenotypic data simplifies the exploration of large data sets, thereby improving breeding decision making. Data are imported from text files; in addition data exchange with other software packages (FlexQTL(TM) and GenomeStudio(TM)) is possible. Instructions for use and an executable version compatible with the Windows platform are available for free from http://www.plantbreeding.wur.nl/UK/software_pedimap.html.

  11. Haplotype and linkage disequilibrium analysis of the CRMP1 and EVC genes.

    Science.gov (United States)

    Sivakumaran, Theru A; Lesperance, Marci M

    2004-11-01

    In this report, we present the haplotype and linkage disequilibrium (LD) pattern in the Collapsin Response Mediator Protein 1 (CRMP1) and Ellis-van Creveld syndrome (EVC) gene region. We genotyped eight different single nucleotide polymorphisms (SNPs) in the CRMP1 and EVC genes in 90 control individuals of diverse ethnicity. The minor allele frequencies ranged from 3.3-49.4%, with most having a frequency >25%. A total of 37 haplotypes were derived from these eight polymorphisms, with only one haplotype having a frequency >10%. Pairwise LD analysis showed a weak but significant LD between markers located about 243 kb apart in this region. The LD was significant between markers spaced about 208 kb apart in EVC, whereas no LD was found between a pair of markers located about 5 kb apart in CRMP1. However, in general, LD correlated with the distance between loci. The CRMP1 and EVC genes are located near WFS1, the Wolfram syndrome type 1 gene, in which mutations also cause low frequency sensorineural hearing loss (LFSNHL). The haplotypes obtained from these polymorphisms will be useful to track the segregation of phenotypes in families with Ellis-van Creveld syndrome, Weyers acrodental dysostosis, LFSNHL and Wolfram syndrome type 1.

  12. Genetic linkage of familial granulomatous inflammatory arthritis, skin rash, and uveitis to chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, G.; Kuivaniemi, H.; Ala-Kokko, L. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1996-11-01

    Blau syndrome (MIM 186580), first described in a large, three-generation kindred, is an autosomal, dominantly inherited disease characterized by multiorgan, tissue-specific inflammation. Its clinical phenotype includes granulomatous arthritis, skin rash, and uveitis and probably represents a subtype of a group of clinical entities referred to as {open_quotes}familial granulomatosis.{close_quotes} It is the sole human model with recognizably Mendelian inheritance for a variety of multisystem inflammatory diseases affecting a significant percentage of the population. A genomewide search for the Blau susceptibility locus was undertaken after karyotypic analysis revealed no abnormalities. Sixty-two of the 74-member pedigree were genotyped with dinucleotide-repeat markers. Linkage analysis was performed under dominant model of inheritance with reduced penetrance. The marker D16S298 gave a maximum LOD score of 3.75 at {theta} = .04, with two-point analysis. LOD scores for flanking markers were consistent and placed the Blau susceptibility locus within the 16p12-q21 interval. 46 refs., 3 figs., 3 tabs.

  13. Single Nucleotide Polymorphisms (SNPs) Discovery and Linkage Disequilibrium (LD) in Forest Trees

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    With completion of the Populus genome sequencing project and the availability of many expressed sequence tags (ESTs) databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium (LD) rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.

  14. Linkage disequilibrium-based quality control for large-scale genetic studies.

    Directory of Open Access Journals (Sweden)

    Paul Scheet

    2008-08-01

    Full Text Available Quality control (QC is a critical step in large-scale studies of genetic variation. While, on average, high-throughput single nucleotide polymorphism (SNP genotyping assays are now very accurate, the errors that remain tend to cluster into a small percentage of "problem" SNPs, which exhibit unusually high error rates. Because most large-scale studies of genetic variation are searching for phenomena that are rare (e.g., SNPs associated with a phenotype, even this small percentage of problem SNPs can cause important practical problems. Here we describe and illustrate how patterns of linkage disequilibrium (LD can be used to improve QC in large-scale, population-based studies. This approach has the advantage over existing filters (e.g., HWE or call rate that it can actually reduce genotyping error rates by automatically correcting some genotyping errors. Applying this LD-based QC procedure to data from The International HapMap Project, we identify over 1,500 SNPs that likely have high error rates in the CHB and JPT samples and estimate corrected genotypes. Our method is implemented in the software package fastPHASE, available from the Stephens Lab website (http://stephenslab.uchicago.edu/software.html.

  15. Triarchic Model of Psychopathy: Origins, Operationalizations, and Observed Linkages with Personality and General Psychopathology.

    Science.gov (United States)

    Patrick, Christopher J; Drislane, Laura E

    2015-12-01

    The triarchic model (Patrick, Fowles, & Krueger, 2009) was formulated to reconcile contrasting conceptions of psychopathy reflected in historic writings and contemporary assessment instruments, and to address persisting unresolved issues in the field. The model conceives of psychopathy as encompassing three distinct but interrelated phenotypic dispositions--disinhibition, boldness, and meanness--with biological referents. These dispositional constructs can be viewed as building blocks for alternative conceptions of psychopathy, and various existing psychopathy measures are presumed to index these constructs to differing degrees. This article summarizes the bases of the triarchic model in the conceptual and empirical literatures on psychopathy, and it describes linkages between the constructs of the model and established structural frameworks for personality and psychological disorders. Alternative methods for indexing the constructs of the model are described, and evidence regarding their interrelations and criterion-related validity is reviewed. Promising aspects of the model for ongoing research on psychopathy are discussed, along with current gaps in knowledge/methods and recommended avenues for future research.

  16. Evolution of zygotic linkage disequilibrium in a finite local population.

    Directory of Open Access Journals (Sweden)

    Xin-Sheng Hu

    Full Text Available One crucial feature of zygotic linkage disequilibrium (LD analysis is its direct use of diploid genotyping data, irrespective of the type of mating system. Previous theories from an evolutionary perspective mainly focus on gametic LD, but the equivalent development for zygotic LD is not available. Here I study the evolution of zygotic LD and the covariances between gametic and zygotic LDs or between distinct zygotic LDs in a finite local population under constant immigration from a continent population. I derive the analytical theory under genetic hitchhiking effects or in a neutral process. Results indicate that zygotic LDs (diploid level are more informative than gametic LD (haploid level in indicating the effects of different evolutionary forces. Zygotic LDs may be greater than or comparable to gametic LD under the epistatic selection process, but smaller than gametic LD under the non epistatic selection process. The covariances between gametic and zygotic LDs are strongly affected by the mating system, linkage distance, and genetic drift effects, but weakly affected by seed and pollen flow and natural selection. The covariances between different zygotic LDs are generally robust to the effects of gene flow, selection, and linkage distance, but sensitive to the effects of genetic drift and mating system. Consistent patterns exist for the covariances between the zygotic LDs for the two-locus genotypes with one common genotype at one locus or without any common genotype at each locus. The results highlight that zygotic LDs can be applied to detecting natural population history.

  17. Linkage between interests and verbal fluency of primary school pupils

    Directory of Open Access Journals (Sweden)

    Maksić Slavica

    2008-01-01

    Full Text Available The incentive for studying the linkage between interests and creativity is based on the results of biographical studies that indicate that highly creative individuals had wider and more intensive interests than their peers already in the period of childhood. In the process of defining interests, the child tests his/her capacities and discovers the domain in which he/she will later provide creative contributions. The subject of this paper is the linkage between interests of primary school pupils and their verbal fluency, as basic characteristic of creative thinking. It was determined that the wideness of the span of interests is positively correlated with verbal fluency, whereby the correlation between interests and verbal fluency is somewhat higher for boys (r= 0.33, p = .007 than for girls (r = 0.24, p = .030. Also, the intensity of scientific interest of boys and girls is significantly correlated with their verbal fluency (for boys: = 0.39; for girls: r=0.35. But, when school achievement is statistically controlled, the correlation between the intensity of scientific interests and verbal fluency remains significant for boys, while it disappears for girls. It was concluded that the results confirmed the theoretical assumptions about the importance of interest in creativity and pointed out to the need for paying attention to the effect of gender. Besides the span and intensity of interests, the domain in which interests are manifested and creativity is measured is also important for the linkage with creativity.

  18. Postmarketing drug surveillance by record linkage in Tayside.

    Science.gov (United States)

    Crombie, I K; Brown, S V; Hamley, J G

    1984-09-01

    The feasibility of conducting postmarketing drug surveillance by record linkage in Tayside was assessed. The key feature of the method is that all hospital discharge data are already computerised by the area health board and may be accessed through the unique community health number (CHNo) which has been allocated to all Tayside residents. The 12 861 prescriptions for cimetidine dispensed in Tayside over a nine month period were collected and the CHNo identified for 76%. These corresponded to 3802 individuals and their discharge data, together with those for an equal number of controls matched by age, sex, and general practitioner were retrieved from the computer. The expected excess of those diseases for which cimetidine is prescribed (peptic ulcer and oesophagitis) was observed. Other drug-disease associations were observed but may have been due to confounding and emphasise the inadequacy of community based controls. The major advantages of record linkage are, firstly, the low cost of the method, the present study costing just over pounds 12 000, and, secondly, the duration of patient follow up which may may be extended for as many years as required simply by rerunning the computer programs. To assemble large patient cohorts the study would have to be extended to other area health boards that are currently developing similar computer systems. Record linkage may provide a cost effective method for the follow up of patients to identify serious adverse drug reactions, particularly those that take several years to develop.

  19. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan;

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...

  20. Integrating binary traits with quantitative phenotypes for association mapping of multivariate phenotypes.

    Science.gov (United States)

    Mukhopadhyay, Indranil; Saha, Sujayam; Ghosh, Saurabh

    2011-01-01

    Clinical binary end-point traits are often governed by quantitative precursors. Hence it may be a prudent strategy to analyze a clinical end-point trait by considering a multivariate phenotype vector, possibly including both quantitative and qualitative phenotypes. A major statistical challenge lies in integrating the constituent phenotypes into a reduced univariate phenotype for association analyses. We assess the performances of certain reduced phenotypes using analysis of variance and a model-free quantile-based approach. We find that analysis of variance is more powerful than the quantile-based approach in detecting association, particularly for rare variants. We also find that using a principal component of the quantitative phenotypes and the residual of a logistic regression of the binary phenotype on the quantitative phenotypes may be an optimal method for integrating a binary phenotype with quantitative phenotypes to define a reduced univariate phenotype. PMID:22373144

  1. Modulation of cardiac myocyte phenotype in vitro by the composition and orientation of the extracellular matrix.

    Science.gov (United States)

    Simpson, D G; Terracio, L; Terracio, M; Price, R L; Turner, D C; Borg, T K

    1994-10-01

    Cellular phenotype is the result of a dynamic interaction between a cell's intrinsic genetic program and the morphogenetic signals that serve to modulate the extent to which that program is expressed. In the present study we have examined how morphogenetic information might be stored in the extracellular matrix (ECM) and communicated to the neonatal heart cell (NHC) by the cardiac alpha 1 beta 1 integrin molecule. A thin film of type I collagen (T1C) was prepared with a defined orientation. This was achieved by applying T1C to the peripheral edge of a 100 mm culture dish. The T1C was then drawn across the surface of the dish in a continuous stroke with a sterile cell scraper and allowed to polymerize. When NHCs were cultured on this substrate, they spread, as a population, along a common axis in parallel with the gel lattice and expressed an in vivo-like phenotype. Individual NHCs displayed an elongated, rod-like shape and disclosed parallel arrays of myofibrils. These phenotypic characteristics were maintained for at least 4 weeks in primary culture. The evolution of this tissue-like organizational pattern was dependent upon specific interactions between the NHCs and the collagen-based matrix that were mediated by the cardiac alpha 1 beta 1 integrin complex. This conclusion was supported by a variety of experimental results. Altering the tertiary structure of the matrix or blocking the extracellular domains of either the cardiac alpha 1 or beta 1 integrin chain inhibited the expression of the tissue-like pattern of organization. Neither cell-to-cell contact or contractile function were necessary to induce the formation of the rod-like cell shape. However, beating activity was necessary for the assembly of a well-differentiated myofibrillar apparatus. These data suggest that the cardiac alpha 1 beta 1 integrin complex serves to detect and transduce phenotypic information stored within the tertiary structure of the surrounding matrix.

  2. Phenotype of villous stromal cells in placentas with cytomegalovirus, syphilis, and nonspecific villitis.

    OpenAIRE

    Greco, M A; Wieczorek, R.; Sachdev, R.; Kaplan, C.; Nuovo, G. J.; Demopoulos, R. I.

    1992-01-01

    Villous stromal cells (VSC) play an important role in fetomaternal placental immune function. We studied the phenotype of VSC in infection by cytomegalovirus (CMV) and syphilis as well as nonspecific villitis and compared the findings with gestational age-matched controls. Monoclonal antibodies directed against total leukocytes, T cells, B cells, macrophages, dendritic cells, granulocytes and HLA-DR as well as polyclonal antibodies against S-100, alpha-1 antichymotrypsin, and lysozyme were us...

  3. Effect of pH on subunit association and heat protection of soybean alpha-galactosidase

    Science.gov (United States)

    Porter, J. E.; Sarikaya, A.; Herrmann, K. M.; Ladisch, M. R.; Mitchell, C. A. (Principal Investigator)

    1992-01-01

    Soybeans contain the enzyme alpha-galactosidase, which hydrolyzes alpha-1, 6 linkages in stachyose and raffinose to give sucrose and galactose. We have found that galactose, a competitive product inhibitor of alpha-galactosidase, strongly promotes the heat stability of the tetrameric form of the enzyme at pH 4.0 and at temperatures of up to 70 degrees C for 60 min. Stachyose and raffinose also protect alpha-galactosidase from denaturation at pH 4.0 although to a lesser extent. Glucose and mannose have little effect. At pH 7.0 the enzyme is a monomer, and galactose has no effect on the heat stability of the enzyme. In the absence of heat protection of the enzyme by added sugars, a series deactivation mechanism was found to describe the deactivation data. In comparison, a unimolecular, non-first order deactivation model applies at pH 4.0, where heat protection effects were observed. At a temperature above 60 degrees C, simple deactivation is a suitable model. The results suggest that alpha-galactosidase conformation and heat stability are directly related.

  4. Multivariate Analysis of Genotype-Phenotype Association.

    Science.gov (United States)

    Mitteroecker, Philipp; Cheverud, James M; Pavlicev, Mihaela

    2016-04-01

    With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map

  5. Linkage Analysis of Cement Industry in the Indonesian Economy: Input-Output Analysis

    Directory of Open Access Journals (Sweden)

    Muhammad Mirza

    2015-11-01

    Full Text Available This study aims to determine the relations of backward and forward linkages of cement industry on the various economic sectors in Indonesia. In analyzing the relations, Indonesia’s input-output table of year 2005 isusedwhich is based ontheIndonesian domestic transactions on the basis of the producer price of 175 sectors classification. The results showed that the cement industry has backward linkages to the 43 sectors (5 sectors that have the biggest backward linkage are: the coal sector, electricity and gas sector, natural gas and geothermal sectors,excavation goods and oil refining goods and has forward linkages to 15 sectors (5 sectors that have the biggest forward linkage, namely: agricultural infrastructure sector, roads, bridges and ports, goods from non-metallic materials, residential and non-residental buildings, the building sector and the installation of electricity, gas, water and communication, in the direct linkages, both backward and forward linkages of cement industry are still considered as low, and the total linkages of the cement industry has stronger association with upstream sector when compared to the downstream sector. The conditions of the backward linkages of cement industry in 2014 is assumed to be relatively the same as those in 2005, while the forward linkage in 2014 indicates a shift in the sectors that have the biggest linkage to the cement industry.

  6. Genetic linkage heterogeneity in the fragile X syndrome.

    Science.gov (United States)

    Brown, W T; Gross, A C; Chan, C B; Jenkins, E C

    1985-01-01

    Genetic linkage between a factor IX DNA restriction fragment length polymorphism (RFLP) and the fragile X chromosome marker was analyzed in eight fragile X pedigrees and compared to eight previously reported pedigrees. A large pedigree with apparently full penetrance in all male members showed a high frequency of recombination. A lod score of -7.39 at theta = 0 and a maximum score of 0.26 at theta = 0.32 were calculated. A second large pedigree with a nonpenetrant male showed tight linkage with a maximum lod score of 3.13 at theta = 0, a result similar to one large pedigree with a nonpenetrant male previously reported. The differences in lod scores seen in these large pedigrees suggested there was genetic heterogeneity in linkage between families which appeared to relate to the presence of nonpenetrant males. The combined lod score for the three pedigrees with nonpenetrant males was 6.84 at theta = 0. For the 13 other pedigrees without nonpenetrant males the combined lod score was -21.81 at theta = 0, with a peak of 0.98 at theta = 0.28. When lod scores from all 16 families were combined, the value was -15.14 at theta = 0 and the overall maximum was 5.13 at theta = 0.17. To determine whether genetic heterogeneity was present, three statistical tests for heterogeneity were employed. First, a "predivided-sample" test was used. The 16 pedigrees were divided into two classes, NP and P, based upon whether or not any nonpenetrant males were detected in the pedigree. This test gave evidence for significant genetic heterogeneity whether the three large pedigrees with seven or more informative males (P less than 0.005), the eight pedigrees with three informative males (P less than 0.001), or all 16 pedigrees (P less than 0.001) were included in the analysis. Second, Morton's large sample test was employed. Significant heterogeneity was present when the analysis was restricted to the three large pedigrees (P less than 0.025), or to the eight pedigrees with informative males

  7. Molecular cloning and characterization of a plant alpha1,3/4-fucosidase based on sequence tags from almond fucosidase I.

    Science.gov (United States)

    Zeleny, Reinhard; Leonard, Renaud; Dorfner, Georg; Dalik, Thomas; Kolarich, Daniel; Altmann, Friedrich

    2006-04-01

    Our work with almond peptide N-glycosidase A made us interested also in the alpha1,3/4-fucosidase which is used as a specific reagent for glycoconjugate analysis. The enzyme was purified to presumed homogeneity by a series of chromatographic steps including dye affinity and fast-performance anion exchange chromatography. The 63 kDa band was analyzed by tandem mass spectrometry which yielded several partial sequences. A homology search retrieved the hypothetical protein Q8GW72 from Arabidopsis thaliana. This protein has recently been described as being specific for alpha1,2-linkages. However, cDNA cloning and expression in Pichia pastoris of the A. thaliana fucosidase showed that it hydrolyzed fucose in 3- and 4-linkage to GlcNAc in Lewis determinants whereas neither 2-linked fucose nor fucose in 3-linkage to the innermost GlcNAc residue were attacked. This first cloning of a plant alpha1,3/4-fucosidase also confirmed the identity of the purified almond enzyme and thus settles the notorious uncertainty about its molecular mass. The alpha1,3/4-fucosidase from Arabidopsis exhibited striking sequence similarity with an enzyme of similar substrate specificity from Streptomyces sp. (Q9Z4I9) and with putative proteins from rice. PMID:16516937

  8. Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework.

    Science.gov (United States)

    Fanous, A H; Kendler, K S

    2005-01-01

    Schizophrenia has long been thought to be clinically heterogeneous. A range of studies suggests that this is due to genetic heterogeneity. Some clinical features, such as negative symptoms, are associated with a greater risk of illness in relatives. Affected sibling pairs are correlated for clinical and course features as well as subforms of illness, and twin studies suggest that this is due to genetic factors. This is further supported by findings that subjects from families linked to some chromosomal regions may differ clinically from those from unlinked families. Moreover, some genes may affect clinical features without altering susceptibility (ie are modifier genes). High-risk genotypes may have quantitative, rather than categorical effects, and may influence milder or subclinical phenotypes. Another recent finding is that nonpsychotic relatives may have personality features that resemble those of their affected relatives. These findings taken together suggest that there may be several classes of gene action in schizophrenia: some genes may influence susceptibility only, others may influence clinical features only, and still others may have a mixed effect. Furthermore, subsets of these classes may affect personality and other traits in nonpsychotic relatives. Understanding these classes of gene action may help guide the design of linkage and association studies that have increased power. We describe five classes of genes and their predictions of the outcomes of family, twin, and several types of linkage studies. We go on to explore how these predictions can in turn be used to aid in the design of linkage studies.

  9. A Test of Outreach and Drop-in Linkage Versus Shelter Linkage for Connecting Homeless Youth to Services.

    Science.gov (United States)

    Slesnick, Natasha; Feng, Xin; Guo, Xiamei; Brakenhoff, Brittany; Carmona, Jasmin; Murnan, Aaron; Cash, Scottye; McRee, Annie-Laurie

    2016-05-01

    Outreach and service linkage are key for engaging marginalized populations, such as homeless youth, in services. Research to date has focused primarily on engaging individuals already receiving some services through emergency shelters, clinics, or other programs. Less is known about those who are not connected to services and, thus, likely the most vulnerable and in need of assistance. The current study sought to engage non-service-connected homeless youth (N = 79) into a strengths-based outreach and advocacy intervention. Youth were randomly assigned to receive 6 months of advocacy that focused on linking youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). All youth were assessed at baseline and 3, 6, and 9 months post-baseline. Findings indicated that youth prefer drop-in center services to the shelter. Also, the drop-in center linkage condition was associated with more service linkage overall (B = 0.34, SE = 0.04, p homeless youth. PMID:26759145

  10. Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies

    DEFF Research Database (Denmark)

    Leu, Costin; de Kovel, Carolien G F; Zara, Federico;

    2012-01-01

    Purpose: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1...... ancestry including 982 relatives with GGEs. To dissect out seizure type-related susceptibility genes, two family subgroups were stratified comprising 235 families with predominantly genetic absence epilepsies (GAEs) and 118 families with an aggregation of juvenile myoclonic epilepsy (JME). To map shared....... Phenotype-genotype strategies applying narrow trait definitions in phenotypic homogeneous subgroups of families improve the prospects of disentangling the genetic basis of common familial GGE syndromes....

  11. EGF AND TGF ALPHA EXPRESSION INFLUENCE THE DEVELOPMENTAL TOXICITY OF TCDD: DOSE RESPONSE AND AHR PHENOTYPE IN EGF, TGF ALPHA AND EGF+TGF ALPHA KNOCKOUT MICE

    Science.gov (United States)

    Abstract The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces cleft palate (CP) and hydronephrosis (HN) in mice. The etiology of these defects involves hyperproliferation of epithelial cells of the secondary palatal shelf and ureter, respectively. ...

  12. RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages

    DEFF Research Database (Denmark)

    von Wichert, Gotz; Jiang, Guoying; Kostic, Ana;

    2003-01-01

    -integrins at the leading edge during early spreading, and coimmunoprecipitates with alphav-integrins during spreading on fibronectin and vitronectin. RPTPalpha-dependent activation of Src family kinases, in particular activation of Fyn, is required for the force-dependent formation of focal complexes and...

  13. ER-alpha-cDNA as part of a bicistronic transcript gives rise to high frequency, long term, receptor expressing cell clones.

    Directory of Open Access Journals (Sweden)

    Michal Shenfeld

    Full Text Available Within the large group of Estrogen Receptor alpha (ERα-negative breast cancer patients, there is a subgroup carrying the phenotype ERα(-, PR(-, and Her2(-, named accordingly "Triple-Negative" (TN. Using cell lines derived from this TN group, we wished to establish cell clones, in which ERα is ectopically expressed, forming part of a synthetic lethality screening system. Initially, we generated cell transfectants expressing a mono-cistronic ERα transcription unit, adjacent to a separate dominant selectable marker transcription unit. However, the yield of ERα expressing colonies was rather low (5-12.5%, and only about half of these displayed stable ectopic ERα expression over time. Generation and maintenance of such cell clones under minimal exposure to the ERα ligand, did not improve yield or expression stability. Indeed, other groups have also reported grave difficulties in obtaining ectopic expression of ERα in ERα-deficient breast carcinoma cells. We therefore switched to transfecting these cell lines with pERα-IRES, a plasmid vector encoding a bicistronic translation mRNA template: ERα Open Reading Frame (ORF being upstream followed by a dominant-positive selectable marker (hygro(R ORF, directed for translation from an Internal Ribosome Entry Site (IRES. Through usage of this bicistronic vector linkage system, it was possible to generate a very high yield of ERα expressing cell clones (50-100%. The stability over time of these clones was also somewhat improved, though variations between individual cell clones were evident. Our successful experience with ERα in this system may serve as a paradigm for other genes where ectopic expression meets similar hardships.

  14. Associations of polymorphisms in the promoter I of bovine acetyl-CoA carboxylase-alpha gene with beef fatty acid composition.

    Science.gov (United States)

    Zhang, S; Knight, T J; Reecy, J M; Wheeler, T L; Shackelford, S D; Cundiff, L V; Beitz, D C

    2010-08-01

    The objectives of this study were to identify single nucleotide polymorphisms (SNPs) in the promoter I (PI) region of the bovine acetyl-CoA carboxylase-alpha (ACACA) gene and to evaluate the extent to which they were associated with lipid-related traits. Eight novel SNPs were identified, which were AJ276223:g.2064T>A (SNP1), g.2155C>T (SNP2), g.2203G>T (SNP3), g.2268T>C (SNP4), g.2274G>A (SNP5), g.2340A>G (SNP6), g.2350T>C (SNP7) and g.2370A>G (SNP8). Complete linkage disequilibrium was observed among SNP1, 2, 4, 5, 6 and 8. Phenotypic data were collected from 573 cross-bred steers with six sire breeds, including Hereford, Angus, Brangus, Beefmaster, Bonsmara and Romosinuano. The genotypes of SNP1/2/4/5/6/8 were significantly associated with adjusted backfat thickness. The genotypes of SNP3 were significantly associated with triacylglycerol (TAG) content and fatty acid composition of longissimus dorsi muscle (LM) in Brangus-, Romosinuano- and Bonsmara-sired cattle. Cattle with g.2203GG genotype had greater concentrations of TAG, total lipid, total saturated fatty acid and total monounsaturated fatty acid than did cattle with g.2203GT genotype. The genotypes of SNP7 were significantly associated with fatty acid composition of LM. Cattle with genotype g.2350TC had greater amounts of several fatty acids in LM than did cattle with genotype g.2350CC. Our results suggested that the SNPs in the PI region of ACACA gene are associated with variations in the fatty acid contents in LM. PMID:20002363

  15. Myocardial phenotypic changes in Na+, K+ ATPase in left ventricular hypertrophy: pharmacological consequences.

    Science.gov (United States)

    Charlemagne, D; Swynghedauw, B

    1995-05-01

    Cardiac adaptation to permanent overload induces several phenotypic changes which finally result in a system which works more economically, together with a slower Vmax. The molecular target of digitalis is the NA+, K+ ATPase, which is a polymorphic molecule. We have recently demonstrated that during cardiac hypertrophy this target is modified and that a shift occurs in the alpha 1 subunit, from the normally present alpha 2 isosubunit to alpha 3, which is a fetal isoform with a lower affinity for sodium and a higher affinity for ouabain. Such a shift explains why, in rat cardiac hypertrophy ouabain is less toxic than normal and is released from its target more slowly. It may also explain at least in part the discrepancies observed in clinical trials on the efficacy of digitalis. PMID:7556267

  16. Gaseous alpha emitter diffusion studies using alpha track method

    International Nuclear Information System (INIS)

    Using a very accurate and sensitive analysis method such as alpha track method, the SSNTD group was able to undertake studies on the atomic and molecular processes taking place at low speed and/or very low concentrations, such as diffusion of gaseous alpha radionuclides in gaseous media. For practical application reasons, we began to study the diffusion in air for gaseous alpha radionuclides and aerosols carrying solid alpha radionuclides. The used alpha radionuclides were: Rn-222, as gaseous radionuclide and its solid descendants genetically related, attached to different particles from air, as radioactive aerosols. The source was included into an air tight device with a very well known volume. After 40 days, the radioactive equilibrium was established for all descendants, so that in the device there were the Rn-222 and its descendants, each of them having the same activity. The relative amount/activity ratio of each decay product, at any duration, for any initial mass of Ra-226 parent radionuclide, were calculated using the code UURASE, based on the Bateman general equations, for computing the U-238 radioactive series gamma accumulation. This was adapted for alpha accumulation as ALFAURASE programme. The device which contains the Ra-226 source can be coupled to the calibration system or to the diffusion system, without destroying the radioactive equilibrium. At this coupling, only the radioactive concentration is changed due to the variation of the volume. First of all the device was used for calibrating the CR-39 track detectors for both Rn-222 gaseous radionuclide and aerosol concentration measurements using, in the coupled calibration system, a special 'detector-container' equipped/or not with a filter used for radioactive aerosol stopping. The track detectors CR-39 were etched in NaOH 30%, for 7 hours at 70 deg. C and their studies were performed by optical microscopy using a stereo-microscope Wild M7S and a binocular Zeiss Jena microscope. (authors)

  17. Characterization of vascular smooth muscle cell phenotype in long-term culture.

    Science.gov (United States)

    Absher, M; Woodcock-Mitchell, J; Mitchell, J; Baldor, L; Low, R; Warshaw, D

    1989-02-01

    Studies of bovine carotid artery smooth muscle cells, during long-term in vitro subcultivation (up to 100 population doublings), have revealed phenotypic heterogeneity among cells, as characterized by differences in proliferative behavior, cell morphology, and contractile-cytoskeletal protein profiles. In vivo, smooth muscle cells were spindle-shaped and expressed desmin and alpha-smooth muscle actin (50% of total actin) as their predominant cytoskeletal and contractile proteins. Within 24 h of culture, vimentin rather than desmin was the predominant intermediate filament protein, with little change in alpha-actin content. Upon initial subcultivation, all cells were flattened and fibroblastic in appearance with a concomitant fivefold reduction in alpha-actin content, whereas the beta and gamma nonmuscle actins predominated. In three out of four cell lines studied, fluctuations in proliferative activity were observed during the life span of the culture. These spontaneous fluctuations in proliferation were accompanied by coordinated changes in morphology and contractile-cytoskeletal protein profiles. During periods of enhanced proliferation a significant proportion of cells reverted to their original spindle-shaped morphology with a simultaneous increase in alpha-actin content (20 to 30% of total actin). These results suggest that in long-term culture smooth muscle cells undergo spontaneous modulations in cell phenotype and may serve as a useful model for studying the regulation of intracellular protein expression.

  18. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  19. Workshop on Precision Measurements of $\\alpha_s$

    Energy Technology Data Exchange (ETDEWEB)

    Bethke, Siegfried; /Munich, Max Planck Inst.; Hoang, Andre H.; /Vienna U.; Kluth, Stefan; /Munich, Max Planck Inst.; Schieck, Jochen; /Munich U.; Stewart, Iain W.; Aoki, S.; Beneke, M.; Bethke, S.; Blumlein, J.; Brambilla, N.; Brodsky, S.; /MIT, LNS

    2011-10-01

    These are the proceedings of the Workshop on Precision Measurements of {alpha}{sub s} held at the Max-Planck-Institute for Physics, Munich, February 9-11, 2011. The workshop explored in depth the determination of {alpha}{sub s}(m{sub Z}) in the {ovr MS} scheme from the key categories where high precision measurements are currently being made, including DIS and global PDF fits, {tau}-decays, electro-weak precision observables and Z-decays, event-shapes, and lattice QCD. These proceedings contain a short summary contribution from the speakers, as well as the lists of authors, conveners, participants, and talks.

  20. Analysis of Pena Shokeir phenotype.

    Science.gov (United States)

    Hall, J G

    1986-09-01

    At this point in time, we recognize that "Pena Shokeir" is not a diagnosis or a specific syndrome but rather a description of a phenotype produced by fetal akinesia or decreased in utero movement. In its "full blown" form, it is characterized by polyhydramnios, intrauterine growth retardation, pulmonary hypoplasia, craniofacial and limb anomalies, congenital contractures, short umbilical cord, and lethality. From the cases thus far reported, we would anticipate that the phenotype is present in a very heterogeneous group of disorders--heterogeneous both with regard to the specific anomalies present and with regard to the causes (which must include many environmental agents and multiple genetic forms). One challenge for the future is to better describe and delineate specific entities. In the meantime, we would do well to use the terms "Pena Shokeir phenotype" or "fetal akinesia/hypokinesia sequence," which do not imply a single entity. There are many practical aspects of recognizing this phenotype. The presence of any one of the cardinal signs of the fetal akinesia/hypokinesia sequence should alert the physician to look for the other associated anomalies, since specific treatment may be indicated, and catch-up or compensatory growth may occur, if given a chance. The ability to provide prenatal diagnosis and perhaps prenatal treatment in the future may allow us to alter dramatically the natural history of some cases. In others, we need to establish when treatment is possible and when it gives no benefit. Perhaps the most important insight gained from the study of the fetal akinesia sequence is the reaffirmation of the concept that function is an integral part of normal development. Specific structures do not develop in isolation but are part of a carefully timed and integrated system. The "use" of a structure in utero is necessary for its continuing and normal development. The old adage "use it or lose it" seems to apply just as appropriately to prenatal normal

  1. Hemogoblin phenotypes in Murgese horse

    OpenAIRE

    Carmela Bottiglieri; Rosario Rullo; Aldo Di Luccia; Elisa Pieragostini

    2010-01-01

    In this note we describe two new equine hemoglobin phenotypes found during a survey of the Murgese horse, a rare  Apulian native breed, among whose ancestors the Arabian surely plays an important role. To date we have analysed about  300 individual hemolysates by different chromatographic analyses (PAGIF, IPG, CMC). The results pointed out two unusu-  al patterns where the ratio of the α24Phe60Gln band to the α24Phe60Lys band was 93:7 and 70:30 rather than 60:40&nbs...

  2. Genome-wide patterns of recombination, linkage disequilibrium and nucleotide diversity from pooled resequencing and single nucleotide polymorphism genotyping unlock the evolutionary history of Eucalyptus grandis.

    Science.gov (United States)

    Silva-Junior, Orzenil B; Grattapaglia, Dario

    2015-11-01

    We used high-density single nucleotide polymorphism (SNP) data and whole-genome pooled resequencing to examine the landscape of population recombination (ρ) and nucleotide diversity (ϴw ), assess the extent of linkage disequilibrium (r(2) ) and build the highest density linkage maps for Eucalyptus. At the genome-wide level, linkage disequilibrium (LD) decayed within c. 4-6 kb, slower than previously reported from candidate gene studies, but showing considerable variation from absence to complete LD up to 50 kb. A sharp decrease in the estimate of ρ was seen when going from short to genome-wide inter-SNP distances, highlighting the dependence of this parameter on the scale of observation adopted. Recombination was correlated with nucleotide diversity, gene density and distance from the centromere, with hotspots of recombination enriched for genes involved in chemical reactions and pathways of the normal metabolic processes. The high nucleotide diversity (ϴw = 0.022) of E. grandis revealed that mutation is more important than recombination in shaping its genomic diversity (ρ/ϴw = 0.645). Chromosome-wide ancestral recombination graphs allowed us to date the split of E. grandis (1.7-4.8 million yr ago) and identify a scenario for the recent demographic history of the species. Our results have considerable practical importance to Genome Wide Association Studies (GWAS), while indicating bright prospects for genomic prediction of complex phenotypes in eucalypt breeding.

  3. Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping

    Science.gov (United States)

    Zhang, Yu; Cui, Min; Zhang, Jimin; Zhang, Lei; Li, Chenliu; Kan, Xin; Sun, Qian; Deng, Dexiang; Yin, Zhitong

    2016-01-01

    Maize grain contamination with aflatoxin from Aspergillus flavus (A. flavus) is a serious health hazard to animals and humans. To map the quantitative trait loci (QTLs) associated with resistance to A. flavus, we employed a powerful approach that differs from previous methods in one important way: it combines the advantages of the genome-wide association analysis (GWAS) and traditional linkage mapping analysis. Linkage mapping was performed using 228 recombinant inbred lines (RILs), and a highly significant QTL that affected aflatoxin accumulation, qAA8, was mapped. This QTL spanned approximately 7 centi-Morgan (cM) on chromosome 8. The confidence interval was too large for positional cloning of the causal gene. To refine this QTL, GWAS was performed with 558,629 single nucleotide polymorphisms (SNPs) in an association population comprising 437 maize inbred lines. Twenty-five significantly associated SNPs were identified, most of which co-localised with qAA8 and explained 6.7% to 26.8% of the phenotypic variation observed. Based on the rapid linkage disequilibrium (LD) and the high density of SNPs in the association population, qAA8 was further localised to a smaller genomic region of approximately 1500 bp. A high-resolution map of the qAA8 region will be useful towards a marker-assisted selection (MAS) of A. flavus resistance and a characterisation of the causal gene. PMID:27598199

  4. Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2016-09-01

    Full Text Available Maize grain contamination with aflatoxin from Aspergillus flavus (A. flavus is a serious health hazard to animals and humans. To map the quantitative trait loci (QTLs associated with resistance to A. flavus, we employed a powerful approach that differs from previous methods in one important way: it combines the advantages of the genome-wide association analysis (GWAS and traditional linkage mapping analysis. Linkage mapping was performed using 228 recombinant inbred lines (RILs, and a highly significant QTL that affected aflatoxin accumulation, qAA8, was mapped. This QTL spanned approximately 7 centi-Morgan (cM on chromosome 8. The confidence interval was too large for positional cloning of the causal gene. To refine this QTL, GWAS was performed with 558,629 single nucleotide polymorphisms (SNPs in an association population comprising 437 maize inbred lines. Twenty-five significantly associated SNPs were identified, most of which co-localised with qAA8 and explained 6.7% to 26.8% of the phenotypic variation observed. Based on the rapid linkage disequilibrium (LD and the high density of SNPs in the association population, qAA8 was further localised to a smaller genomic region of approximately 1500 bp. A high-resolution map of the qAA8 region will be useful towards a marker-assisted selection (MAS of A. flavus resistance and a characterisation of the causal gene.

  5. Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping.

    Science.gov (United States)

    Zhang, Yu; Cui, Min; Zhang, Jimin; Zhang, Lei; Li, Chenliu; Kan, Xin; Sun, Qian; Deng, Dexiang; Yin, Zhitong

    2016-01-01

    Maize grain contamination with aflatoxin from Aspergillus flavus (A. flavus) is a serious health hazard to animals and humans. To map the quantitative trait loci (QTLs) associated with resistance to A. flavus, we employed a powerful approach that differs from previous methods in one important way: it combines the advantages of the genome-wide association analysis (GWAS) and traditional linkage mapping analysis. Linkage mapping was performed using 228 recombinant inbred lines (RILs), and a highly significant QTL that affected aflatoxin accumulation, qAA8, was mapped. This QTL spanned approximately 7 centi-Morgan (cM) on chromosome 8. The confidence interval was too large for positional cloning of the causal gene. To refine this QTL, GWAS was performed with 558,629 single nucleotide polymorphisms (SNPs) in an association population comprising 437 maize inbred lines. Twenty-five significantly associated SNPs were identified, most of which co-localised with qAA8 and explained 6.7% to 26.8% of the phenotypic variation observed. Based on the rapid linkage disequilibrium (LD) and the high density of SNPs in the association population, qAA8 was further localised to a smaller genomic region of approximately 1500 bp. A high-resolution map of the qAA8 region will be useful towards a marker-assisted selection (MAS) of A. flavus resistance and a characterisation of the causal gene. PMID:27598199

  6. Involvement of vacuolar sequestration and active transport in tolerance of Saccharomyces cerevisiae to hop iso-alpha-acids.

    Science.gov (United States)

    Hazelwood, Lucie A; Walsh, Michael C; Pronk, Jack T; Daran, Jean-Marc

    2010-01-01

    The hop plant, Humulus lupulus L., has an exceptionally high content of secondary metabolites, the hop alpha-acids, which possess a range of beneficial properties, including antiseptic action. Studies performed on the mode of action of hop iso-alpha-acids have hitherto been restricted to lactic acid bacteria. The present study investigated molecular mechanisms of hop iso-alpha-acid resistance in the model eukaryote Saccharomyces cerevisiae. Growth inhibition occurred at concentrations of hop iso-alpha-acids that were an order of magnitude higher than those found with hop-tolerant prokaryotes. Chemostat-based transcriptome analysis and phenotype screening of the S. cerevisiae haploid gene deletion collection were used as complementary methods to screen for genes involved in hop iso-alpha-acid detoxification and tolerance. This screening and further analysis of deletion mutants confirmed that yeast tolerance to hop iso-alpha-acids involves three major processes, active proton pumping into the vacuole by the vacuolar-type ATPase to enable vacuolar sequestration of iso-alpha-acids and alteration of cell wall structure and, to a lesser extent, active export of iso-alpha-acids across the plasma membrane. Furthermore, iso-alpha-acids were shown to affect cellular metal homeostasis by acting as strong zinc and iron chelators.

  7. Pseudovitamin D deficient rickets (PDDR). Linkage disequilibrium mapping in young populations

    Energy Technology Data Exchange (ETDEWEB)

    Labuda, M.; Korab-Laskowska, M.; Labuda, D. [McGill Univ. (Canada)] [and others

    1994-09-01

    PDDR is an autosomal recessive disorder with elevated prevalence in French Canadians. The condition is believed to be due to a deficient renal 25(OH)-vitamin D 1-alpha hydroxylase, but its underlying molecular defect is unknown. By linkage analysis we have earlier mapped PDDR to human chromosome 12q14. Using recently developed microsatellite markers we narrowed down the disease locus to a 5.6 cM interval between two clusters of loci: 234tf12, 207yh10, 249vf9, 329zh9, on proximal, and 259zc9 and 184yf2 on the distal side. Further refinement of the PDDR locus was obtained from analysis of those markers on 85 French Canadian PDDR chromosomes by linkage disequilibrium (LD). Ten-marker haplotype analysis for all chromosomes allowed to divide this sample into two groups, one of Saguenay-Lac St. Jean-Charlevoix (SLSJ-Ch), the other from Nova Scotia and New Brunswick (NS, NB). All SLSJ-Ch PDDR chromosomes shared an identical haplotype for markers 172x38, 184yf2, 259zc9, pointing to a single founder in this population. In the NS, NB group, the founder effect was also pronounced; however, the link of 2 PDDR chromosomes to either of these groups remains to be elucidated. In the absence of recombination in 12 generations of the SLSJ-Ch population, the genetic distance between PDDR and markers 172xd8, 184yf2, 259zc9 was estimated to be less than 0.4 cM. Finally the marker 207va9 was found to be the closest proximal one based on one recombination in a Polish PDDR family, its CEPH map position as well as its localization on the same YAC together with the distal markers 184yf2, 309xh1 and the marker 172xd8, probably the closest to the PDDR gene. Our study clearly shows the potential of LD for mapping human disorders in populations as young as 10-12 generations. Here it allowed narrowing PDDR position down to a single YAC.

  8. The Role of ATRX in the Alternative Lengthening of Telomeres (ALT Phenotype

    Directory of Open Access Journals (Sweden)

    João P. Amorim

    2016-09-01

    Full Text Available Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT. The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX or Death-Domain Associated Protein (DAXX genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype.

  9. The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype.

    Science.gov (United States)

    Amorim, João P; Santos, Gustavo; Vinagre, João; Soares, Paula

    2016-01-01

    Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) or Death-Domain Associated Protein (DAXX) genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype). PMID:27657132

  10. The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype

    Science.gov (United States)

    Amorim, João P.; Santos, Gustavo; Vinagre, João; Soares, Paula

    2016-01-01

    Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) or Death-Domain Associated Protein (DAXX) genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype). PMID:27657132

  11. Development of a black gram [Vigna mungo (L.) Hepper] linkage map and its comparison with an azuki bean [Vigna angularis (Willd.) Ohwi and Ohashi] linkage map.

    Science.gov (United States)

    Chaitieng, B; Kaga, A; Tomooka, N; Isemura, T; Kuroda, Y; Vaughan, D A

    2006-11-01

    The Asian Vigna group of grain legumes consists of six domesticated species, among them black gram is widely grown in South Asia and to a lesser extent in Southeast Asia. We report the first genetic linkage map of black gram [Vigna mungo (L.) Hepper], constructed using a BC(1)F(1) population consisting of 180 individuals. The BC(1)F(1) population was analyzed in 61 SSR primer pairs, 56 RFLP probes, 27 AFLP loci and 1 morphological marker. About 148 marker loci could be assigned to the 11 linkage groups, which correspond to the haploid chromosome number of black gram. The linkage groups cover a total of 783 cM of the black gram genome. The number of markers per linkage group ranges from 6 to 23. The average distance between adjacent markers varied from 3.5 to 9.3 cM. The results of comparative genome mapping between black gram and azuki bean show that the linkage order of markers is highly conserved. However, inversions, insertions, deletions/duplications and a translocation were detected between the black gram and azuki bean linkage maps. The marker order on parts of linkage groups 1, 2 and 5 is reversed between the two species. One region on black gram linkage group 10 appears to correspond to part of azuki bean linkage group 1. The present study suggests that the azuki bean SSR markers can be widely used for Asian Vigna species and the black gram genetic linkage map will assist in improvement of this crop.

  12. Characterization of the casein gene complex in West African goats and description of a new alpha(s1)-casein polymorphism.

    Science.gov (United States)

    Caroli, A; Chiatti, F; Chessa, S; Rignanese, D; Ibeagha-Awemu, E M; Erhardt, G

    2007-06-01

    The analysis of casein polymorphisms was carried out in West Africa goat populations: Red Sokoto (n = 57), West African Dwarf Nigeria (n = 27), West African Dwarf Cameroon (n = 39), and Borno (n = 37). The 4 casein genes alpha(s1) (CSN1S1), beta (CSN2), alpha(s2) (CSN1S2), and kappa (CSN3) were typed at the DNA level. No null alleles were found in any of the genes analyzed. A PCR single-strand conformation polymorphism method was implemented for the identification of CSN1S1*F allele simultaneously with A/0(1), B/E, N and the new allele. The allele differed from CSN1S1*B by a synonymous transversion TCG-->TCT in the codon corresponding to Ser(66) of the mature protein. The new allele, named CSN1S1*B', occurred at a high frequency in all the populations, ranging from 0.295 (West African Dwarf Cameroon) to 0.405 (Borno). A greater frequency was found for alleles associated with high alpha(s1)-casein quantity, as has already been observed in the goat populations from the Mediterranean area. The intermediate E allele occurred only in the Red Sokoto and at a low frequency. The faint F allele occurred in 3 populations at frequencies lower than 0.03. Linkage disequilibrium occurred in all the populations, with highly significant differences in Borno, Red Sokoto, and West Africa Dwarf Nigeria, and significant differences in West Africa Dwarf Cameroon. Only 10 haplotypes showed frequencies > or =0.05 in at least 1 of the 4 populations considered, and the overall frequency was >0.1 only for 4 haplotypes: BAAB, B'ACA, ACAB, and BACA (in the order CSN1S1-CSN2-CSN1S2-CSN3). Haplotype BAAB, postulated as an ancestral haplotype in previous studies, was the most common haplotype in all breeds except Borno, where B'ACA was predominant. The results obtained are of considerable significance given that very little information exists on the subject for African goats. The high frequency of strong alleles in the calcium-sensitive caseins as well as the high linkage disequilibrium found

  13. Conditioning of alpha bearing wastes

    International Nuclear Information System (INIS)

    Alpha bearing wastes are generated during the reprocessing of spent fuel, mixed oxide fuel fabrication, decommissioning and other activities. The safe and effective management of these wastes is of particular importance owing to the radiotoxicity and long lived characteristics of certain transuranic (TRU) elements. The management of alpha bearing wastes involves a number of stages which include collection, characterization, segregation, treatment, conditioning, transport, storage and disposal. This report describes the currently available matrices and technologies for the conditioning of alpha wastes and relates them to their compatibility with the other stages of the waste management process. The selection of a specific immobilization process is dependent on the waste treatment state and the subsequent handling, transport, storage and disposal requirements. The overall objectives of immobilization are similar for all waste producers and processors, which are to produce: (a) Waste forms with sufficient mechanical, physical and chemical stability to satisfy all stages of handling, transport and storage (referred to as the short term requirements), and (b) Waste forms which will satisfy disposal requirements and inhibit the release of radionuclides to the biosphere (referred to as the long term requirements). Cement and bitumen processes have already been successfully applied to alpha waste conditioning on the industrial scale in many of the IAEA Member States. Cement systems based on BFS and pozzolanic cements have emerged as the principal encapsulation matrices for the full range of alpha bearing wastes. Alternative technologies, such as polymers and ceramics, are being developed for specific waste streams but are unlikely to meet widespread application owing to cost and process complexity. The merits of alpha waste conditioning are improved performance in transport, storage and disposal combined with enhanced public perception of waste management operations. These

  14. A High-Density SNP Genetic Linkage Map and QTL Analysis of Growth-Related Traits in a Hybrid Family of Oysters (Crassostrea gigas × Crassostrea angulata Using Genotyping-by-Sequencing

    Directory of Open Access Journals (Sweden)

    Jinpeng Wang

    2016-05-01

    Full Text Available Oysters are among the most important species in global aquaculture. Crassostrea gigas, and its subspecies C. angulata, are the major cultured species. To determine the genetic basis of growth-related traits in oysters, we constructed a second-generation linkage map from 3367 single-nucleotide polymorphisms (SNPs based on genotyping-by-sequencing, genotyped from a C. gigas × C. angulata hybrid family. These 3367 SNPs were distributed on 1695 markers, which were assigned to 10 linkage groups. The genetic linkage map had a total length of 1084.3 cM, with an average of 0.8 cM between markers; it thus represents the densest genetic map constructed for oysters to date. Twenty-seven quantitative trait loci (QTL for five growth-related traits were detected. These QTL could explain 4.2–7.7% (mean = 5.4% of the phenotypic variation. In total, 50.8% of phenotypic variance for shell width, 7.7% for mass weight, and 34.1% for soft tissue weight were explained. The detected QTL were distributed among eight linkage groups, and more than half (16 were concentrated within narrow regions in their respective linkage groups. Thirty-eight annotated genes were identified within the QTL regions, two of which are key genes for carbohydrate metabolism. Other genes were found to participate in assembly and regulation of the actin cytoskeleton, signal transduction, and regulation of cell differentiation and development. The newly developed high-density genetic map, and the QTL and candidate genes identified provide a valuable genetic resource and a basis for marker-assisted selection for C. gigas and C. angulata.

  15. Modelling neuroinflammatory phenotypes in vivo

    Directory of Open Access Journals (Sweden)

    Wyss-Coray Tony

    2004-07-01

    Full Text Available Abstract Inflammation of the central nervous system is an important but poorly understood part of neurological disease. After acute brain injury or infection there is a complex inflammatory response that involves activation of microglia and astrocytes and increased production of cytokines, chemokines, acute phase proteins, and complement factors. Antibodies and T lymphocytes may be involved in the response as well. In neurodegenerative disease, where injury is more subtle but consistent, the inflammatory response is continuous. The purpose of this prolonged response is unclear, but it is likely that some of its components are beneficial and others are harmful. Animal models of neurological disease can be used to dissect the specific role of individual mediators of the inflammatory response and assess their potential benefit. To illustrate this approach, we discuss how mutant mice expressing different levels of the cytokine transforming growth factor β-1 (TGF-β1, a major modulator of inflammation, produce important neuroinflammatory phenotypes. We then demonstrate how crosses of TGF-β1 mutant mice with mouse models of Alzheimer's disease (AD produced important new information on the role of inflammation in AD and on the expression of different neuropathological phenotypes that characterize this disease.

  16. Phenotypic plasticity in bacterial plasmids.

    Science.gov (United States)

    Turner, Paul E

    2004-01-01

    Plasmid pB15 was previously shown to evolve increased horizontal (infectious) transfer at the expense of reduced vertical (intergenerational) transfer and vice versa, a key trade-off assumed in theories of parasite virulence. Whereas the models predict that susceptible host abundance should determine which mode of transfer is selectively favored, host density failed to mediate the trade-off in pB15. One possibility is that the plasmid's transfer deviates from the assumption that horizontal spread (conjugation) occurs in direct proportion to cell density. I tested this hypothesis using Escherichia coli/pB15 associations in laboratory serial culture. Contrary to most models of plasmid transfer kinetics, my data show that pB15 invades static (nonshaking) bacterial cultures only at intermediate densities. The results can be explained by phenotypic plasticity in traits governing plasmid transfer. As cells become more numerous, the plasmid's conjugative transfer unexpectedly declines, while the trade-off between transmission routes causes vertical transfer to increase. Thus, at intermediate densities the plasmid's horizontal transfer can offset selection against plasmid-bearing cells, but at high densities pB15 conjugates so poorly that it cannot invade. I discuss adaptive vs. nonadaptive causes for the phenotypic plasticity, as well as potential mechanisms that may lead to complex transfer dynamics of plasmids in liquid environments. PMID:15166133

  17. Capillary regeneration in scleroderma: stem cell therapy reverses phenotype?

    Directory of Open Access Journals (Sweden)

    Jo N Fleming

    Full Text Available BACKGROUND: Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS: We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue, antiangiogenic interferon alpha (overexpressed in the scleroderma dermis and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon alpha and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal. CONCLUSION/SIGNIFICANCE: These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease

  18. Prioritizing tiger conservation through landscape genetics and habitat linkages.

    Directory of Open Access Journals (Sweden)

    Bibek Yumnam

    Full Text Available Even with global support for tiger (Panthera tigris conservation their survival is threatened by poaching, habitat loss and isolation. Currently about 3,000 wild tigers persist in small fragmented populations within seven percent of their historic range. Identifying and securing habitat linkages that connect source populations for maintaining landscape-level gene flow is an important long-term conservation strategy for endangered carnivores. However, habitat corridors that link regional tiger populations are often lost to development projects due to lack of objective evidence on their importance. Here, we use individual based genetic analysis in combination with landscape permeability models to identify and prioritize movement corridors across seven tiger populations within the Central Indian Landscape. By using a panel of 11 microsatellites we identified 169 individual tigers from 587 scat and 17 tissue samples. We detected four genetic clusters within Central India with limited gene flow among three of them. Bayesian and likelihood analyses identified 17 tigers as having recent immigrant ancestry. Spatially explicit tiger occupancy obtained from extensive landscape-scale surveys across 76,913 km(2 of forest habitat was found to be only 21,290 km(2. After accounting for detection bias, the covariates that best explained tiger occupancy were large, remote, dense forest patches; large ungulate abundance, and low human footprint. We used tiger occupancy probability to parameterize habitat permeability for modeling habitat linkages using least-cost and circuit theory pathway analyses. Pairwise genetic differences (FST between populations were better explained by modeled linkage costs (r>0.5, p<0.05 compared to Euclidean distances, which was in consonance with observed habitat fragmentation. The results of our study highlight that many corridors may still be functional as there is evidence of contemporary migration. Conservation efforts should

  19. Co-movements of and Linkages between Asian Stock Markets

    Directory of Open Access Journals (Sweden)

    Joe H. Kim,

    2012-01-01

    Full Text Available International marketers may be interested in stock market linkages for various reasons: the co-movements of equity prices appear to reflect not only market globalization but also the globalization of capital resources. The co-movements can affect the balancing strategies of country market portfolios as they indicate opportunities and risks. The strategic choice of alternative market presence, such as market entry via export marketing or a full ownership and marketing may need to match with the type of financial resources. The co-movements of and the linkages between the U.S. stock market and Asian stock markets have been studied extensively. However, little attention has been given to the co-movements of Asian stock markets and the lead/lag linkages between them. In this paper, we study this issue with the principal components analysis (PCA and Granger-causality (G-C statistical techniques. We find that the contemporaneous co-movements of Asian stock markets have become closer and portfolio diversification benefits with Asian stock markets have diminished over time during the January 1, 2001-January 1, 2011 period. We find that the Singapore, Indian, and Japanese stock markets are the most influential stock markets and the Philippine and South Korean stock markets are the least influential stock markets in Asia. The Japanese, Singapore, and New Zealand stock markets are the least affected stock markets and the Shanghai, Australian, and South Korean stock markets are the most affected stock markets by the movements in the other Asian stock markets.

  20. Detection of tandam duplications and implications for linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Matise, T.C.; Weeks, D.E. (Univ. of Pittsburgh, PA (United States)); Chakravarti, A. (Case Western Reserve Univ., Cleveland, OH (United States)); Patel, P.I.; Lupski, J.R. (Baylor College of Medicine, Houston, TX (United States)); Nelis, E.; Timmerman, V.; Van Broeckhoven, C. (Univ. of Antwerp (Belgium))

    1994-06-01

    The first demonstration of an autosomal dominant human disease caused by segmental trisomy came in 1991 for Charcot-Marie-Tooth disease type 1A (CMT1A). For this disorder, the segmental trisomy is due to a large tandem duplication of 1.5 Mb of DNA located on chromosome 17p11.2-p12. The search for the CMT1A disease gene was misdirected and impeded because some chromosome 17 genetic markers that are linked to CMT1A lie within this duplication. To better understand how such a duplication might affect genetic analyses in the context of disease gene mapping, the authors studied the effects of marker duplication on transmission probabilities of marker alleles, on linkage analysis of an autosomal dominant disease, and on tests of linkage homogeneity. They demonstrate that the undetected presence of a duplication distorts transmission ratios, hampers fine localization of the disease gene, and increases false evidence of linkage heterogeneity. In addition, they devised a likelihood-based method for detecting the presence of a tandemly duplicated marker when one is suspected. They tested their methods through computer simulations and on CMT1A pedigrees genotyped at several chromosome 17 markers. On the simulated data, the method detected 96% of duplicated markers (with a false-positive rate of 5%). On the CMT1A data the method successfully identified two of three loci that are duplicated (with no false positives). This method could be used to identify duplicated markers in other regions of the genome and could be used to delineate the extent of duplications similar to that involved in CMT1A. 18 refs., 5 figs., 6 tabs.

  1. Test chamber for alpha spectrometry

    Science.gov (United States)

    Larsen, Robert P.

    1977-01-01

    Alpha emitters for low-level radiochemical analysis by measurement of alpha spectra are positioned precisely with respect to the location of a surface-barrier detector by means of a chamber having a removable threaded planchet holder. A pedestal on the planchet holder holds a specimen in fixed engagement close to the detector. Insertion of the planchet holder establishes an O-ring seal that permits the chamber to be pumped to a desired vacuum. The detector is protected against accidental contact and resulting damage.

  2. Modelling and visualizing fine-scale linkage disequilibrium structure

    DEFF Research Database (Denmark)

    Edwards, David

    2013-01-01

    Background Detailed study of genetic variation at the population level in humans and other species is now possible due to the availability of large sets of single nucleotide polymorphism data. Alleles at two or more loci are said to be in linkage disequilibrium (LD) when they are correlated...... the methods they are applied to data obtained by genotyping 8341 pigs. It is found that roughly 20% of the porcine genome exhibits complex LD patterns, forming islands of relatively high genetic diversity. Conclusions The proposed algorithm is efficient and makes it feasible to estimate and visualize...

  3. Learning and Competence Building through Cross-cultural Linkages

    DEFF Research Database (Denmark)

    Sørensen, Olav Jull

    2006-01-01

    The aim of the chapter is to study upgrading of companies in developing countries in a learning perspective. Both formal and experiential and tacit knowledge is discussed. Learning effects of different management modes, expatriates, linkages to customers and suppliers are discussed as are learning...... thorugh actual production as well as through explicit transfer of knowledge. The chapter in this way makes an attempt to provide an overview of the multiplicity og learning interfaces. It is concluded that the learning perspective need to be adressed more both by managers and scholars....

  4. Performance prediction for windmills with linkage-guided blades

    Energy Technology Data Exchange (ETDEWEB)

    Nahas, M.N.; Akyurt, M. (Mechanical Engineering Dept., King Abdul Aziz Univ., Jeddah (SA))

    1992-01-01

    Three windmills with linkage-guided blades that were previously described by the authors are future studied to predict their performance. The present paper concentrates on the guiding mechanisms of the active power producing surfaces (or blades) and on the output torque. Also investigated here is the effect of the orientation of these blades with respect to their guiding links. The fluctuation in the output torque of one-blade windmills has led to the investigation of the output torque that can be obtained from three-bladed machines. These latter windmills are found to reduce the fluctuation in the output torque considerably. Areas for further improvement are discussed.

  5. STARVATION RESISTANCE IN DROSOPHILA-MELANOGASTER IN RELATION TO THE POLYMORPHISMS AT THE ADH AND ALPHA-GPDH LOCI

    NARCIS (Netherlands)

    OUDMAN, L; VANDELDEN, W; KAMPING, A; BIJLSMA, R

    1994-01-01

    In view of the world-wide latitudinal cline of the Adh and alpha Gpdh allozyme frequencies of Drosophila melanogaster and the interactions between these loci, experiments were performed to study the phenotypic effects of these loci. Starvation resistance, oxygen consumption, body weight, protein con

  6. Identification and outcomes of clinical phenotypes in amyotrophic lateral sclerosis/motor neuron disease: Australian National Motor Neuron Disease observational cohort

    Science.gov (United States)

    Talman, Paul; Duong, Thi; Vucic, Steve; Mathers, Susan; Venkatesh, Svetha; Henderson, Robert; Rowe, Dominic; Schultz, David; Edis, Robert; Needham, Merrilee; Macdonnell, Richard; McCombe, Pamela; Birks, Carol; Kiernan, Matthew

    2016-01-01

    Objective To capture the clinical patterns, timing of key milestones and survival of patients presenting with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) within Australia. Methods Data were prospectively collected and were timed to normal clinical assessments. An initial registration clinical report form (CRF) and subsequent ongoing assessment CRFs were submitted with a completion CRF at the time of death. Design Prospective observational cohort study. Participants 1834 patients with a diagnosis of ALS/MND were registered and followed in ALS/MND clinics between 2005 and 2015. Results 5 major clinical phenotypes were determined and included ALS bulbar onset, ALS cervical onset and ALS lumbar onset, flail arm and leg and primary lateral sclerosis (PLS). Of the 1834 registered patients, 1677 (90%) could be allocated a clinical phenotype. ALS bulbar onset had a significantly lower length of survival when compared with all other clinical phenotypes (p<0.004). There were delays in the median time to diagnosis of up to 12 months for the ALS phenotypes, 18 months for the flail limb phenotypes and 19 months for PLS. Riluzole treatment was started in 78–85% of cases. The median delays in initiating riluzole therapy, from symptom onset, varied from 10 to 12 months in the ALS phenotypes and 15–18 months in the flail limb phenotypes. Percutaneous endoscopic gastrostomy was implemented in 8–36% of ALS phenotypes and 2–9% of the flail phenotypes. Non-invasive ventilation was started in 16–22% of ALS phenotypes and 21–29% of flail phenotypes. Conclusions The establishment of a cohort registry for ALS/MND is able to determine clinical phenotypes, survival and monitor time to key milestones in disease progression. It is intended to expand the cohort to a more population-based registry using opt-out methodology and facilitate data linkage to other national registries. PMID:27694488

  7. Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a Danish five-generation family with a novel FAM83H nonsense mutation.

    Science.gov (United States)

    Haubek, Dorte; Gjørup, Hans; Jensen, Lillian G; Juncker, Inger; Nyegaard, Mette; Børglum, Anders D; Poulsen, Sven; Hertz, Jens M

    2011-11-01

    BACKGROUND.  Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES.  The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study the phenotypic variation of the enamel in affected family members. RESULTS.  Significant linkage was found to a locus at chromosome 8q24.3 comprising the gene FAM83H identified to be responsible for ADHCAI in other families. Subsequent sequencing of FAM83H in affected family members revealed a novel nonsense mutation, p.Y302X. Limited phenotypic variation was found among affected family members with loss of translucency and discoloration of the enamel. Extensive posteruptive loss of enamel was found in all teeth of affected subjects. The tip of the cusps on the premolars and molars and a zone along the gingival margin seemed resistant to posteruptive loss of enamel. We have screened FAM83H in another five unrelated Danish patients with a phenotype of ADHCAI similar to that in the five-generation family, and identified a de novo FAM83H nonsense mutation, p.Q452X in one of these patients. CONCLUSION.  We have identified a FAM83H mutation in two of six unrelated families with ADHCAI and found limited phenotypic variation of the enamel in these patients.

  8. Inflaton Decay in an Alpha Vacuum

    CERN Document Server

    Naidu, S; Naidu, Siddartha; Holman, Richard

    2004-01-01

    We study the alpha vacua of de Sitter space by considering the decay rate of the inflaton field coupled to a scalar field placed in an alpha vacuum. We find an {\\em alpha dependent} Bose enhancement relative to the Bunch-Davies vacuum and, surprisingly, no non-renormalizable divergences. We also consider a modified alpha dependent time ordering prescription for the Feynman propagator and show that it leads to an alpha independent result. This result suggests that it may be possible to calculate in any alpha vacuum if we employ the appropriate causality preserving prescription.

  9. Deletional rearrangement in the human T-cell receptor. cap alpha. -chain locus

    Energy Technology Data Exchange (ETDEWEB)

    de Villartay, J.P.; Lewis, D.; Hockett, R.; Waldmann, T.A.; Korsmeyer, S.J.; Cohen, D.I.

    1987-12-01

    The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed ..cap alpha.. and ..beta... In the course of characterizing human T-cell tumors with an immature (CD4/sup -/, CD8/sup -/) surface phenotype, the authors detected a 2-kilobase ..cap alpha..-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early ..cap alpha..) located between the ..cap alpha..-chain variable- and joining-region genes had been spliced to the ..cap alpha.. constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the ..cap alpha.. gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature ..cap alpha.. gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the ..gamma..delta heterodimeric receptor and is deleted from mature (..cap alpha beta..-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (..gamma..delta-expressing) T cells and mature (..cap alpha beta..-expressing) T cells.

  10. Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

    Directory of Open Access Journals (Sweden)

    Xin Li

    Full Text Available Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage analysis on a 5-generation Chinese pedigree with isolated bilateral microtia. We identified a suggestive linkage locus on 4p15.32-4p16.2 with parametric LOD score of 2.70 and nonparametric linkage score (Zmean of 12.28 (simulated occurrence per genome scan equal to 0.46 and 0.47, respectively. Haplotype reconstruction analysis of the 4p15.32-4p16.2 region further confined the linkage signal to a 10-Mb segment located between rs12505562 and rs12649803 (9.65-30.24 cM; 5.54-15.58 Mb. Various human organ developmental genes reside in this 10-Mb susceptibility region, such as EVC, EVC2, SLC2A9, NKX3-2, and HMX1. The coding regions of three genes, EVC known for cartilage development and NKX3-2, HMX1 involved in microtia, were selected for sequencing with 5 individuals from the pedigree. Of the 38 identified sequence variants, none segregates along with the disease phenotype. Other genes or DNA sequences of the 10-Mb region warrant for further investigation. In conclusion, we report a susceptibility locus of isolated microtia, and this finding will encourage future studies on the genetic basis of ear deformity.

  11. Further analysis of previously implicated linkage regions for Alzheimer's disease in affected relative pairs

    Directory of Open Access Journals (Sweden)

    Lannfelt Lars

    2009-12-01

    Full Text Available Abstract Background Genome-wide linkage studies for Alzheimer's disease have implicated several chromosomal regions as potential loci for susceptibility genes. Methods In the present study, we have combined a selection of affected relative pairs (ARPs from the UK and the USA included in a previous linkage study by Myers et al. (Am J Med Genet, 2002, with ARPs from Sweden and Washington University. In this total sample collection of 397 ARPs, we have analyzed linkage to chromosomes 1, 9, 10, 12, 19 and 21, implicated in the previous scan. Results The analysis revealed that linkage to chromosome 19q13 close to the APOE locus increased considerably as compared to the earlier scan. However, linkage to chromosome 10q21, which provided the strongest linkage in the previous scan could not be detected. Conclusion The present investigation provides yet further evidence that 19q13 is the only chromosomal region consistently linked to Alzheimer's disease.

  12. Record linkage to correct under-ascertainment of cancers in HIV cohorts: The Sinikithemba HIV clinic linkage project.

    Science.gov (United States)

    Sengayi, Mazvita; Spoerri, Adrian; Egger, Matthias; Kielkowski, Danuta; Crankshaw, Tamaryn; Cloete, Christie; Giddy, Janet; Bohlius, Julia

    2016-09-15

    The surveillance of HIV-related cancers in South Africa is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. To improve cancer ascertainment and estimate cancer incidence, we linked records of adults (aged ≥ 16 years) on antiretroviral treatment (ART) enrolled at Sinikithemba HIV clinic, McCord Hospital in KwaZulu-Natal (KZN) with the cancer records of public laboratories in KZN province using probabilistic record linkage (PRL) methods. We calculated incidence rates for all cancers, Kaposi sarcoma (KS), cervix, non-Hodgkin's lymphoma and non-AIDS defining cancers (NADCs) before and after inclusion of linkage-identified cancers with 95% confidence intervals (CIs). A total of 8,721 records of HIV-positive patients were linked with 35,536 cancer records. Between 2004 and 2010, we identified 448 cancers, 82% (n = 367) were recorded in the cancer registry only, 10% (n = 43) in the HIV cohort only and 8% (n = 38) both in the HIV cohort and the cancer registry. The overall cancer incidence rate in patients starting ART increased from 134 (95% CI 91-212) to 877 (95% CI 744-1,041) per 100,000 person-years after inclusion of linkage-identified cancers. Incidence rates were highest for KS (432, 95% CI 341-555), followed by cervix (259, 95% CI 179-390) and NADCs (294, 95% CI 223-395) per 100,000 person-years. Ascertainment of cancer in HIV cohorts is incomplete, PRL is both feasible and essential for cancer ascertainment. PMID:27098265

  13. What Powers Lyman alpha Blobs?

    CERN Document Server

    Ao, Y; Beelen, A; Henkel, C; Cen, R; De Breuck, C; Francis, P; Kovacs, A; Lagache, G; Lehnert, M; Mao, M; Menten, K M; Norris, R; Omont, A; Tatemastu, K; Weiss, A; Zheng, Z

    2015-01-01

    Lyman alpha blobs (LABs) are spatially extended lyman alpha nebulae seen at high redshift. The origin of Lyman alpha emission in the LABs is still unclear and under debate. To study their heating mechanism(s), we present Australia Telescope Compact Array (ATCA) observations of the 20 cm radio emission and Herschel PACS and SPIRE measurements of the far-infrared (FIR) emission towards the four LABs in the protocluster J2143-4423 at z=2.38. Among the four LABs, B6 and B7 are detected in the radio with fluxes of 67+/-17 microJy and 77+/-16 microJy, respectively, and B5 is marginally detected at 3 sigma (51+/-16 microJy). For all detected sources, their radio positions are consistent with the central positions of the LABs. B6 and B7 are obviously also detected in the FIR. By fitting the data with different templates, we obtained redshifts of 2.20$^{+0.30}_{-0.35}$ for B6 and 2.20$^{+0.45}_{-0.30}$ for B7 which are consistent with the redshift of the lyman alpha emission within uncertainties, indicating that both ...

  14. Alpha Testing Escape from Diab

    Science.gov (United States)

    Alpha testing was conducted of sessions 2 and 3 from Diab to assess whether the activities worked as expected, and whether children in the target ages enjoyed it. Data include both RA observations of child performance while playing the games and cognitive interview responses from the players after t...

  15. HLA region excluded by linkage analyses of early onset periodontitis

    Energy Technology Data Exchange (ETDEWEB)

    Sun, C.; Wang, S.; Lopez, N.

    1994-09-01

    Previous studies suggested that HLA genes may influence susceptibility to early-onset periodontitis (EOP). Segregation analyses indicate that EOP may be due to a single major gene. We conducted linkage analyses to assess possible HLA effects on EOP. Fifty families with two or more close relatives affected by EOP were ascertained in Virginia and Chile. A microsatellite polymorphism within the HLA region (at the tumor necrosis factor beta locus) was typed using PCR. Linkage analyses used a donimant model most strongly supported by previous studies. Assuming locus homogeneity, our results exclude a susceptibility gene within 10 cM on either side of our marker locus. This encompasses all of the HLA region. Analyses assuming alternative models gave qualitatively similar results. Allowing for locus heterogeneity, our data still provide no support for HLA-region involvement. However, our data do not statistically exclude (LOD <-2.0) hypotheses of disease-locus heterogeneity, including models where up to half of our families could contain an EOP disease gene located in the HLA region. This is due to the limited power of even our relatively large collection of families and the inherent difficulties of mapping genes for disorders that have complex and heterogeneous etiologies. Additional statistical analyses, recruitment of families, and typing of flanking DNA markers are planned to more conclusively address these issues with respect to the HLA region and other candidate locations in the human genome. Additional results for markers covering most of the human genome will also be presented.

  16. A population genetics model of linkage disequilibrium in admixed populations

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Understanding linkage disequilibrium (LD) created in admixed population and the rate of decay in the disequilibrium over evolution is an important subject in population genetics theory and in disease gene mapping in human populations. The present study represents the theoretical investigation of effects of gene frequencies, levels of LD and admixture proportions of donor populations on the evolutionary dynamics of the LD of the admixed population. We examined the conditions under which the admixed population reached linkage equilibrium or the peak level of the LD. The study reveals the inappropriateness in approximating the dynamics of the LD generated by population admixture by the commonly used formula in literature. An appropriate equation for the dynamics is proposed. The distinct feature of the newly suggested formula is that the value of the nonlinear component of the LD remains constant in the first generation of the population evolution. Comparison between the predicted disequilibrium dynamics shows that the error will be caused by using the old formula, and thus resulting in a misguidance in using the evolutionary information of the admixed population in gene mapping.

  17. Optimizing Opt-Out Consent for Record Linkage

    Directory of Open Access Journals (Sweden)

    Das Marcel

    2014-09-01

    Full Text Available This article reports on a study testing the effects of different ways of administering an opt-out consent for record linkage in a probability-based Internet panel. First, we conducted cognitive interviews to explore reactions to a draft version of the opt-out consent text. Second, we conducted a two-factor experiment to test the effects of content manipulations and mode. The results indicate that the way in which respondents were informed did not have much effect on opting out. Results from a follow-up survey on attitudes regarding privacy, confidentiality, and trust, along with knowledge questions about the process of linking, showed no evidence that presenting the opt-out consent statement makes respondents more concerned about privacy. Knowledge about the aspects of record linkage is generally not high. When looking at long-term effects of sending an opt-out consent statement, we found no evidence that this leads to higher attrition or lower participation rates.

  18. Thiocyanate linkage isomerism in a ruthenium polypyridyl complex.

    Science.gov (United States)

    Brewster, Timothy P; Ding, Wendu; Schley, Nathan D; Hazari, Nilay; Batista, Victor S; Crabtree, Robert H

    2011-12-01

    Ruthenium polypyridyl complexes have seen extensive use in solar energy applications. One of the most efficient dye-sensitized solar cells produced to date employs the dye-sensitizer N719, a ruthenium polypyridyl thiocyanate complex. Thiocyanate complexes are typically present as an inseparable mixture of N-bound and S-bound linkage isomers. Here we report the synthesis of a new complex, [Ru(terpy)(tbbpy)SCN][SbF(6)] (terpy = 2,2';6',2''-terpyridine, tbbpy = 4,4'-di-tert-butyl-2,2'-bipyridine), as a mixture of N-bound and S-bound thiocyanate linkage isomers that can be separated based on their relative solubility in ethanol. Both isomers have been characterized spectroscopically and by X-ray crystallography. At elevated temperatures the isomers equilibrate, the product being significantly enriched in the more thermodynamically stable N-bound form. Density functional theory analysis supports our experimental observation that the N-bound isomer is thermodynamically preferred, and provides insight into the isomerization mechanism. PMID:22066656

  19. Tropical glaciers and climate dynamics: Resolving the linkages

    Science.gov (United States)

    Mölg, Thomas

    2013-04-01

    Large-scale atmosphere/ocean circulation and mountain glaciers represent two entirely different scales in the climate system. Therefore, statistical linkages between the two mask a cascade of processes that act on different temporal and spatial dimensions. Low-latitude glaciers are particularly well suited for studying such processes, since these glaciers are situated in the "heart" of the global climate system (the tropics). This presentation gives an overview of a decade of research on tropical climate and glaciers on Kilimanjaro (East Africa), which is, to our knowledge, the only case where space/time linkages between high-altitude glaciers and climate dynamics have been investigated systematically throughout the main scales. This includes the complex modification of atmospheric flow when air masses impinge on high mountains, an aspect that has been widely neglected from a cryospheric viewpoint. The case of Kilimanjaro demonstrates (1) the great potential of learning about climate system processes and their connections, (2) advances in our understanding of the importance of moisture for glaciers that lie far above the mean freezing level, and (3) methodological advances in combining atmospheric and cryospheric modelling.

  20. Linkage of familial dilated cardiomyopathy to chromosome 9

    Energy Technology Data Exchange (ETDEWEB)

    Krajinovic, M.; Vatta, M.; Milasin, J. [Univ. of Trieste (Italy)] [and others

    1995-10-01

    Idiopathic dilated cardiomyopathy is a heart muscle disease of unknown etiology, characterized by impaired myocardial contractility and ventricular dilatation. The disorder is an important cause of morbidity and mortality and represents the chief indication for heart transplantation. Familial transmission is often recognized (familial dilated cardiomyopathy, or FDC), mostly with autosomal dominant inheritance. In order to understand the molecular genetic basis of the disease, a large six-generation kindred with autosomal dominant FDC was studied for linkage analysis. A genome-wide search was undertaken after a large series of candidate genes were excluded and was then extended to two other families with autosomal dominant pattern of transmission and identical clinical features. Coinheritance of the disease gene was excluded for >95% of the genome, after 251 polymorphic markers were analyzed. Linkage was found for chromosome 9q13-q22, with a maximum multipoint lod score of 4.2. There was no evidence of heterogeneity. The FDC locus was placed in the interval between loci D9S153 and D9S152. Several candidate genes for causing dilated cardiomyopathy map in this region. 33 refs., 3 figs., 1 tab.

  1. Hemogoblin phenotypes in Murgese horse

    Directory of Open Access Journals (Sweden)

    Carmela Bottiglieri

    2010-01-01

    Full Text Available In this note we describe two new equine hemoglobin phenotypes found during a survey of the Murgese horse, a rare  Apulian native breed, among whose ancestors the Arabian surely plays an important role. To date we have analysed about  300 individual hemolysates by different chromatographic analyses (PAGIF, IPG, CMC. The results pointed out two unusu-  al patterns where the ratio of the α24Phe60Gln band to the α24Phe60Lys band was 93:7 and 70:30 rather than 60:40  which would have been expected of BII homozygote. Given that the three horses exhibiting the unusual patterns shared  a common ancestor and that none of the possible combinations of the known haplotypes can account for 7-8%  α24Phe60Lys, reasonably a triplicated arrangement has to be postulated. 

  2. Cost Analysis of Enhancing Linkages to HIV Care Following Jail: A Cost-Effective Intervention

    OpenAIRE

    Spaulding, Anne C.; Pinkerton, Steven D.; Superak, Hillary; Cunningham, Marc J.; Resch, Stephen; Jordan, Alison O.; Yang, Zhou

    2013-01-01

    We are not aware of published cost-effectiveness studies addressing community transitional programs for HIV-infected jail detainees. To address this gap, data from 9 sites of EnhanceLink, a project that enrolled HIV-infected releasees from jails across the US, were examined. Figures on the number of clients served, cost of linkage services, number of linkages and 6-month sustained linkages to community HIV care, and number of clients achieving viral suppression were assessed for subjects rele...

  3. Estimating linkage disequilibrium between a polymorphic marker locus and a trait locus in natural populations.

    OpenAIRE

    Luo, Z. W.; Suhai, S.

    1999-01-01

    Positional cloning of gene(s) underlying a complex trait requires a high-resolution linkage map between the trait locus and genetic marker loci. Recent research has shown that this may be achieved through appropriately modeling and screening linkage disequilibrium between the candidate marker locus and the major trait locus. A quantitative genetics model was developed in the present study to estimate the coefficient of linkage disequilibrium between a polymorphic genetic marker locus and a lo...

  4. Genome-wide linkage scans for major depression in individuals with alcohol dependence

    OpenAIRE

    Kuo, Po-Hsiu; Neale, Michael C.; Walsh, Dermot; Patterson, Diana G.; Riley, Brien; Prescott, Carol A.; Kendler, Kenneth S.

    2010-01-01

    Major depression is more prevalent among individuals with alcoholism than in the general population. Twin studies have found a moderate degree of genetic correlation for alcohol dependence (AD) and major depression (MD), suggesting the existence of loci that confer susceptibility to both disorders. The aim of the present study was to conduct genome-wide linkage analyses to identify loci and to replicate prior evidence for linkage to MD, and to search for linkage regions that may confer risk t...

  5. A literature review of record linkage procedures focusing on infant health outcomes

    Directory of Open Access Journals (Sweden)

    Carla Jorge Machado

    2004-04-01

    Full Text Available Record linkage is a powerful tool in assembling information from different data sources and has been used by a number of public health researchers. In this review, we provide an overview of the record linkage methodologies, focusing particularly on probabilistic record linkage. We then stress the purposes and research applications of linking records by focusing on studies of infant health outcomes based on large data sets, and provide a critical review of the studies in Brazil.

  6. Contribution of university-industry linkages (UILs) to tourism clusters: multiple-case studies in Thailand

    OpenAIRE

    Prasunpangsri, Siriluk

    2013-01-01

    This research develops a theoretical framework explaining how University-Industry Linkages (UILs) affect the performance of tourism clusters in Thailand. Significant external and internal factors affecting Thai tourism industry are examined. The research questions are significant given the importance of successful tourism cluster through University-Industry Linkages (UIL). These questions recognized tourism clusters, the role of university, the linkages between university and i...

  7. Top management perceptions of linkages between understanding, accepting and executing strategy: A case study

    OpenAIRE

    Heikkinen, Sara

    2015-01-01

    Top management perceptions of linkages between understanding, accepting and executing strategy: A case study Objective of the Study: The objective of this study was to explore the case company's top management team's perceptions on understanding, accepting and executing strategy and see in what ways these stages are linked and what kind of implications the linkages have. The study aimed to answer one main research question: From the perspective of management, what are the linkages...

  8. Views of healthcare professionals to linkage of routinely collected healthcare data: a systematic literature review

    OpenAIRE

    Hopf, Y.M.; Bond, C.; Francis, J.; Haughney, J; Helms, P J

    2014-01-01

    Objective: To review the literature on the views of healthcare professionals to the linkage of healthcare data and to identify any potential barriers and/or facilitators to participation in a data linkage system. Methods: Published papers describing the views of healthcare professionals (HCPs) to data sharing and linkage were identified by searches of Medline, EMBASE, SCOPUS, CINAHL, and PsychINFO. The searches were limited to papers published in the English language from 2001 to 2011. ...

  9. Linkage analysis of 19 French breast cancer families, with five chromosome 17q markers.

    OpenAIRE

    Mazoyer, S.; Lalle, P.; Narod, S A; Bignon, Y J; Courjal, F.; Jamot, B; Dutrillaux, B; Stoppa-Lyonnett, D; Sobol, H

    1993-01-01

    Nineteen French breast and breast-ovarian cancer families were tested for linkage with five chromosome 17q markers. The five breast-ovarian cancer families as a group give positive evidence for linkage, whereas the 14 breast cancer-only families do not. Heterogeneity of linkage of breast and breast-ovarian cancers is significant in France and supports the existence of more than one susceptibility gene.

  10. Evaluating bias due to data linkage error in electronic healthcare records.

    OpenAIRE

    Harron, K.; WADE, A.; Gilbert, R.; Muller-Pebody, B; Goldstein, H.

    2014-01-01

    Background Linkage of electronic healthcare records is becoming increasingly important for research purposes. However, linkage error due to mis-recorded or missing identifiers can lead to biased results. We evaluated the impact of linkage error on estimated infection rates using two different methods for classifying links: highest-weight (HW) classification using probabilistic match weights and prior-informed imputation (PII) using match probabilities. Methods A gold-standard dataset was crea...

  11. Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression.

    OpenAIRE

    Thigpen, A E; Silver, R I; Guileyardo, J M; Casey, M L; McConnell, J D; Russell, D W

    1993-01-01

    The synthesis of dihydrotestosterone is catalyzed by steroid 5 alpha-reductase isozymes, designated types 1 and 2. Mutation of type 2 results in male pseudohermaphroditism, in which the external genitalia are phenotypically female at birth. Two striking and unexplained features of this disorder are that external genitalia of affected males undergo virilization during puberty and that these individuals have less temporal hair regression. The tissue-specific and developmental expression pattern...

  12. Clinical Asthma Phenotypes and Therapeutic Responses

    OpenAIRE

    Zedan, M.; Attia, G.; Zedan, M. M.; Osman, A; Abo-Elkheir, N.; Maysara, N.; Barakat, T.; Gamil, N.

    2013-01-01

    Asthma is a heterogeneous disease that means not all asthmatics respond to the same treatment. We hypothesize an approach to characterize asthma phenotypes based on symptomatology (shortness of breath (SOB), cough, and wheezy phenotypes) in correlation with airway inflammatory biomarkers and FEV1. We aimed to detect whether those clinical phenotypes have an impact on the response to asthma medications. Two hundred three asthmatic children were allocated randomly to receive either montelukast ...

  13. Latent phenotypes pervade gene regulatory circuits.

    OpenAIRE

    Payne, Joshua L.; Wagner, Andreas

    2014-01-01

    BACKGROUND Latent phenotypes are non-adaptive byproducts of adaptive phenotypes. They exist in biological systems as different as promiscuous enzymes and genome-scale metabolic reaction networks, and can give rise to evolutionary adaptations and innovations. We know little about their prevalence in the gene expression phenotypes of regulatory circuits, important sources of evolutionary innovations. RESULTS Here, we study a space of more than sixteen million three-gene model regulatory circ...

  14. Latent phenotypes pervade gene regulatory circuits

    OpenAIRE

    Payne, Joshua L.; Wagner, Andreas

    2014-01-01

    Background Latent phenotypes are non-adaptive byproducts of adaptive phenotypes. They exist in biological systems as different as promiscuous enzymes and genome-scale metabolic reaction networks, and can give rise to evolutionary adaptations and innovations. We know little about their prevalence in the gene expression phenotypes of regulatory circuits, important sources of evolutionary innovations. Results Here, we study a space of more than sixteen million three-gene model regulatory circuit...

  15. Phenotypes and Survival of Hatchling Lizards

    OpenAIRE

    Warner, Daniel Augustus

    2001-01-01

    The phenotypes of hatchling reptiles are influenced by the environmental conditions that embryos experience during incubation, by yolk invested into the egg, and by the genetic contributions of the parents. Phenotypic traits are influenced by these factors in ways that potentially affect the fitness of hatchlings. The physical conditions that embryos experience within the nest affects development, hatching success, and hatchling phenotypes. Thus, the nest site that a female selects can inf...

  16. Marital assortment and phenotypic convergence: longitudinal evidence.

    Science.gov (United States)

    Caspi, A; Herbener, E S

    1993-01-01

    This study provides a direct test of whether the observed similarity of spouses is due to initial assortment rather than to convergence of phenotypes. With data from three well-known longitudinal studies, phenotypic convergence is examined using both variable- and person-centered analyses. The longitudinal evidence does not support the hypothesis that couples increasingly resemble each other with time. Spouse correlations most likely reflect initial assortment at marriage and not the convergence of phenotypes.

  17. A synopsis of collective alpha effects and implications for ITER

    Energy Technology Data Exchange (ETDEWEB)

    Sigmar, D.J.

    1990-10-01

    This paper discusses the following: Alpha Interaction with Toroidal Alfven Eigenmodes; Alpha Interaction with Ballooning Modes; Alpha Interaction with Fishbone Oscillations; and Implications for ITER.

  18. The EU’s Trade Relations with China (1975-2008): A Linkage Power at Work?

    OpenAIRE

    Zhang, Xiaotong

    2010-01-01

    The EU’s Trade Relations with China (1975-2008): A Linkage Power at Work?(Summary)The central aim of this thesis is to improve our understanding of the EU’s power, in particular in its external trade relations/negotiations. Our hypothesis is that the EU is a distinctive kind of linkage power, defined as an actor relying on linkage as a crucial modus operandi in its external relations. We explored how, to what extent and in which distinctive ways the EU is such a linkage power. Our analysis wa...

  19. Failure to find a chromosome 18 pericentric linkage in families with schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    De Lisi, L.E.; Shields, G. [SUNY Stony Brook, NY (United States); Lehner, T. [Columbia Univ. and New York State Psychiatric Institute, New York, NY (United States)] [and others

    1995-12-18

    A recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small. 12 refs., 4 tabs.

  20. Synthesis of Intermittent-Motion Linkages with Slight Difference in Length Between Links

    Institute of Scientific and Technical Information of China (English)

    CHEN Xin-bo; YU Zhen

    2006-01-01

    The design of intermittent-motion linkages using traditional methods iS usually complicated.In this paper,(1)a new method for realizing intermittent motion,using linkages with a slight difference in length between links,is studied;(2)some new types of intermittent-motion linkages and their software for visual analysis and design are developed;and(3)influences of some design parameters on intermittent.motion characteristics are clarifled.Results confirmed that the theory and the software are useful,making the synthesis of intermittent-motion linkages clear and easy.

  1. Genetic linkage map and comparative genome analysis for the estuarine Atlantic killifish (Fundulus heteroclitus)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Genetic linkage maps are valuable tools in evolutionary biology; however, their availability for wild populations is extremely limited. Fundulus heteroclitus...

  2. Linkage disequilibrium blocks, haplotype structure, and htSNPs of human CYP7A1 gene

    Directory of Open Access Journals (Sweden)

    Wan Yu-Jui

    2006-05-01

    Full Text Available Abstract Background Cholesterol 7-alpha-hydroxylase (CYP7A1 is the rate limiting enzyme for converting cholesterol into bile acids. Genetic variations in the CYP7A1 gene have been associated with metabolic disorders of cholesterol and bile acids, including hypercholesterolemia, hypertriglyceridemia, arteriosclerosis, and gallstone disease. Current genetic studies are focused mainly on analysis of a single nucleotide polymorphism (SNP at A-278C in the promoter region of the CYP7A1 gene. Here we report a genetic approach for an extensive analysis on linkage disequilibrium (LD blocks and haplotype structures of the entire CYP7A1 gene and its surrounding sequences in Africans, Caucasians, Asians, Mexican-Americans, and African-Americans. Result The LD patterns and haplotype blocks of CYP7A1 gene were defined in Africans, Caucasians, and Asians using genotyping data downloaded from the HapMap database to select a set of haplotype-tagging SNPs (htSNP. A low cost, microarray-based platform on thin-film biosensor chips was then developed for high-throughput genotyping to study transferability of the HapMap htSNPs to Mexican-American and African-American populations. Comparative LD patterns and haplotype block structure was defined across all test populations. Conclusion A constant genetic structure in CYP7A1 gene and its surrounding sequences was found that may lead to a better design for association studies of genetic variations in CYP7A1 gene with cholesterol and bile acid metabolism.

  3. Calibration of sources for alpha spectroscopy systems

    International Nuclear Information System (INIS)

    This paper describes the calibration methodology for measuring the total alpha activity of plane and thin sources with the Alpha Spectrometer for Silicon Detector in the Nuclear Measures and Dosimetry laboratory at IEAv/CTA. (author)

  4. Immunogenetic phenotypes in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Marla C Dubinsky; Kent Taylor; Stephan R Targan; Jerome I Rotter

    2006-01-01

    The currently accepted etiopathogenic hypothesis suggests that the chronic intestinal inflammation and related systemic manifestations characteristic of inflammatory bowel disease (IBD) are due to an overly aggressive or pathologic immune response to resident luminal bacterial constituents. Predisposing factors are genetic dysregulation of mucosal immune responses and/or barrier function, with onset triggered by environmental stimuli. These factors and their interactions may also be important determinants of disease phenotype and disease progression. The emergence of immunogenetic phenotypes lends support to the proposed hypothesis that susceptibility genes regulate distinct immune processes, driven by luminal antigens, expressed as specific immune phenotypes which in turn influence clinical phenotypes in IBD patient

  5. Phenotypic plasticity's impacts on diversification and speciation.

    Science.gov (United States)

    Pfennig, David W; Wund, Matthew A; Snell-Rood, Emilie C; Cruickshank, Tami; Schlichting, Carl D; Moczek, Armin P

    2010-08-01

    Phenotypic plasticity (the ability of a single genotype to produce multiple phenotypes in response to variation in the environment) is commonplace. Yet its evolutionary significance remains controversial, especially in regard to whether and how it impacts diversification and speciation. Here, we review recent theory on how plasticity promotes: (i) the origin of novel phenotypes, (ii) divergence among populations and species, (iii) the formation of new species and (iv) adaptive radiation. We also discuss the latest empirical support for each of these evolutionary pathways to diversification and identify potentially profitable areas for future research. Generally, phenotypic plasticity can play a largely underappreciated role in driving diversification and speciation.

  6. Linkage mapping and identification of QTL affecting deoxynivalenol (DON) content (Fusarium resistance) in oats (Avena sativa L.).

    Science.gov (United States)

    He, Xinyao; Skinnes, Helge; Oliver, Rebekah E; Jackson, Eric W; Bjørnstad, Asmund

    2013-10-01

    Mycotoxins caused by Fusarium spp. is a major concern on food and feed safety in oats, although Fusarium head blight (FHB) is often less apparent than in other small grain cereals. Breeding resistant cultivars is an economic and environment-friendly way to reduce toxin content, either by the identification of resistance QTL or phenotypic evaluation. Both are little explored in oats. A recombinant-inbred line population, Hurdal × Z595-7 (HZ595, with 184 lines), was used for QTL mapping and was phenotyped for 3 years. Spawn inoculation was applied and deoxynivalenol (DON) content, FHB severity, days to heading and maturity (DH and DM), and plant height (PH) were measured. The population was genotyped with DArTs, AFLPs, SSRs and selected SNPs, and a linkage map of 1,132 cM was constructed, covering all 21 oat chromosomes. A QTL for DON on chromosome 17A/7C, tentatively designated as Qdon.umb-17A/7C, was detected in all experiments using composite interval mapping, with phenotypic effects of 12.2–26.6 %. In addition, QTL for DON were also found on chromosomes 5C, 9D, 13A, 14D and unknown_3, while a QTL for FHB was found on 11A. Several of the DON/FHB QTL coincided with those for DH, DM and/or PH. A half-sib population of HZ595, Hurdal × Z615-4 (HZ615, with 91 lines), was phenotyped in 2011 for validation of QTL found in HZ595, and Qdon.umb-17A/7C was again localized with a phenotypic effect of 12.4 %. Three SNPs closely linked to Qdon.umb-17A/7C were identified in both populations, and one each for QTL on 5C, 11A and 13A were identified in HZ595. These SNPs, together with those yet to be identified, could be useful in marker-assisted selection to pyramiding resistance QTL.

  7. Two Strategies for Microbial Production of an Industrial Enzyme-Alpha-Amylase

    Science.gov (United States)

    Bernhardsdotter, Eva C. M. J.; Garriott, Owen; Pusey, Marc L.; Ng, Joseph D.

    2003-01-01

    Extremophiles are microorganisms that thrive in, from an anthropocentric view, extreme environments including hot springs, soda lakes and arctic water. This ability of survival at extreme conditions has rendered extremophiles to be of interest in astrobiology, evolutionary biology as well as in industrial applications. Of particular interest to the biotechnology industry are the biological catalysts of the extremophiles, the extremozymes, whose unique stabilities at extreme conditions make them potential sources of novel enzymes in industrial applications. There are two major approaches to microbial enzyme production. This entails enzyme isolation directly from the natural host or creating a recombinant expression system whereby the targeted enzyme can be overexpressed in a mesophilic host. We are employing both methods in the effort to produce alpha-amylases from a hyperthermophilic archaeon (Thermococcus) isolated from a hydrothermal vent in the Atlantic Ocean, as well as from alkaliphilic bacteria (Bacillus) isolated from a soda lake in Tanzania. Alpha-amylases catalyze the hydrolysis of internal alpha-1,4-glycosidic linkages in starch to produce smaller sugars. Thermostable alpha-amylases are used in the liquefaction of starch for production of fructose and glucose syrups, whereas alpha-amylases stable at high pH have potential as detergent additives. The alpha-amylase encoding gene from Thermococcus was PCR amplified using carefully designed primers and analyzed using bioinformatics tools such as BLAST and Multiple Sequence Alignment for cloning and expression in E.coli. Four strains of Bacillus were grown in alkaline starch-enriched medium of which the culture supernatant was used as enzyme source. Amylolytic activity was detected using the starch-iodine method.

  8. Testing a 'genes-to-ecosystems' approach to understanding aquatic-terrestrial linkages.

    Science.gov (United States)

    Crutsinger, Gregory M; Rudman, Seth M; Rodriguez-Cabal, Mariano A; McKown, Athena D; Sato, Takuya; MacDonald, Andrew M; Heavyside, Julian; Geraldes, Armando; Hart, Edmund M; LeRoy, Carri J; El-Sabaawi, Rana W

    2014-12-01

    A 'genes-to-ecosystems' approach has been proposed as a novel avenue for integrating the consequences of intraspecific genetic variation with the underlying genetic architecture of a species to shed light on the relationships among hierarchies of ecological organization (genes → individuals → communities → ecosystems). However, attempts to identify genes with major effect on the structure of communities and/or ecosystem processes have been limited and a comprehensive test of this approach has yet to emerge. Here, we present an interdisciplinary field study that integrated a common garden containing different genotypes of a dominant, riparian tree, Populus trichocarpa, and aquatic mesocosms to determine how intraspecific variation in leaf litter alters both terrestrial and aquatic communities and ecosystem functioning. Moreover, we incorporate data from extensive trait screening and genome-wide association studies estimating the heritability and genes associated with litter characteristics. We found that tree genotypes varied considerably in the quality and production of leaf litter, which contributed to variation in phytoplankton abundances, as well as nutrient dynamics and light availability in aquatic mesocosms. These 'after-life' effects of litter from different genotypes were comparable to the responses of terrestrial communities associated with the living foliage. We found that multiple litter traits corresponding with aquatic community and ecosystem responses differed in their heritability. Moreover, the underlying genetic architecture of these traits was complex, and many genes contributed only a small proportion to phenotypic variation. Our results provide further evidence that genetic variation is a key component of aquatic-terrestrial linkages, but challenge the ability to predict community or ecosystem responses based on the actions of one or a few genes.

  9. Dwarf mutations in grass pea (Lathyrus sativus L.): origin, morphology, inheritance and linkage studies

    Indian Academy of Sciences (India)

    Dibyendu Talukdar

    2009-08-01

    Induction of mutation has been used to create additional genetic variability in grass pea (Lathyrus sativus L.). During the ongoing investigations on different induced-morphological mutants, the author detected three types of dwarf mutants in grass pea. One mutant, designated as dwf1 type was earlier identified in colchicine-induced C2 generation of grass pea variety BioR-231 while the other two, designated as dwf2 and dwf3 were isolated in 250 Gy and 300 Gy gamma ray irradiated M2 progeny of variety ‘BioR-231’ and ‘Hooghly Local’, respectively. As compared to their parental varieties (controls), all the three mutants manifested stunted, erect and determinate stem, early maturity and tolerance to pod shattering habit. The mutants differed from each other, as well as with controls, in number of primary branches, nature of stipules and internodes, length of peduncle, leaflet and seed coat colour, seed yield and seed neurotoxin content. The three dwarf mutants were monogenically recessive and bred true in successive generations. F2 segregation pattern obtained from the crosses involving the three mutants indicated that dwarf mutation in grass pea was controlled by two independent non-allelic genes, assigned as df1 (for dwf1 type), df2 (for dwf2 type) and df3 (for dwf3 type), with the df1 locus being multiple allelic. Primary trisomic analyses revealed the presence of df1/df2 locus on the extra chromosome of trisomic type I, whereas df3 was located on the extra chromosome of type III. Linkage studies involving five other phenotypic markers suggested linked association of df1/df2 locus with lfc (leaflet colour) and wgn (winged internode) and df3 locus with cbl (seed coat colour). Both the loci; however, assorted independently with flower colour and stipule character. The dwarf types can be utilized as valuable tools for further cytogenetic research and breeding of grass pea.

  10. Dwarf mutations in grass pea (Lathyrus sativus L.): origin, morphology, inheritance and linkage studies.

    Science.gov (United States)

    Talukdar, Dibyendu

    2009-08-01

    Induction of mutation has been used to create additional genetic variability in grass pea (Lathyrus sativus L.). During the ongoing investigations on different induced-morphological mutants, the author detected three types of dwarf mutants in grass pea. One mutant, designated as dwf1 type was earlier identified in colchicine-induced C2 generation of grass pea variety BioR-231 while the other two, designated as dwf2 and dwf3 were isolated in 250 Gy and 300 Gy gamma ray irradiated M2 progeny of variety 'BioR-231' and 'Hooghly Local', respectively. As compared to their parental varieties (controls), all the three mutants manifested stunted, erect and determinate stem, early maturity and tolerance to pod shattering habit. The mutants differed from each other, as well as with controls, in number of primary branches, nature of stipules and internodes, length of peduncle, leaflet and seed coat colour, seed yield and seed neurotoxin content. The three dwarf mutants were monogenically recessive and bred true in successive generations. F2 segregation pattern obtained from the crosses involving the three mutants indicated that dwarf mutation in grass pea was controlled by two independent non-allelic genes, assigned as df1 (for dwf1 type), df2 (for dwf2 type) and df3 (for dwf3 type), with the df1 locus being multiple allelic. Primary trisomic analyses revealed the presence of df1/df2 locus on the extra chromosome of trisomic type I, whereas df3 was located on the extra chromosome of type III. Linkage studies involving five other phenotypic markers suggested linked association of df1/df2 locus with lfc (leaflet colour) and wgn (winged internode) and df3 locus with cbl (seed coat colour). Both the loci; however, assorted independently with flower colour and stipule character. The dwarf types can be utilized as valuable tools for further cytogenetic research and breeding of grass pea.

  11. Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.

    Directory of Open Access Journals (Sweden)

    Hasan Alhaddad

    Full Text Available Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r(2 was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r(2 was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r(2 ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r(2 ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds' population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits.

  12. [18F]FDOPA PET as an endophenotype for Parkinson's Disease linkage studies.

    Science.gov (United States)

    Racette, Brad A; Good, Laura; Antenor, Jo Ann; McGee-Minnich, Lori; Moerlein, Stephen M; Videen, Tom O; Perlmutter, Joel S

    2006-04-01

    Parkinson disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies, since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than 3 standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to "PET definite PD." The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14 +/- 0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36 +/- 1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree. PMID:16528749

  13. Enzyme replacement therapy for alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Dali, Christine I.; Fogh, J;

    2013-01-01

    Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly...

  14. Validation of an instrument to measure inter-organisational linkages in general practice

    Directory of Open Access Journals (Sweden)

    Cheryl Amoroso

    2007-11-01

    Full Text Available Purpose: Linkages between general medical practices and external services are important for high quality chronic disease care. The purpose of this research is to describe the development, evaluation and use of a brief tool that measures the comprehensiveness and quality of a general practice’s linkages with external providers for the management of patients with chronic disease. In this study, clinical linkages are defined as the communication, support, and referral arrangements between services for the care and assistance of patients with chronic disease. Methods: An interview to measure surgery-level (rather than individual clinician-level clinical linkages was developed, piloted, reviewed, and evaluated with 97 Australian general practices. Two validated survey instruments were posted to patients, and a survey of locally available services was developed and posted to participating Divisions of General Practice (support organisations. Hypotheses regarding internal validity, association with local services, and patient satisfaction were tested using factor analysis, logistic regression and multilevel regression models. Results: The resulting General Practice Clinical Linkages Interview (GP-CLI is a nine-item tool with three underlying factors: referral and advice linkages, shared care and care planning linkages, and community access and awareness linkages. Local availability of chronic disease services has no affect on the comprehensiveness of services with which practices link, however comprehensiveness of clinical linkages has an association with patient assessment of access, receptionist services, and of continuity of care in their general practice. Conclusions: The GP-CLI may be useful to researchers examining comparable health care systems for measuring the comprehensiveness and quality of linkages at a general practice-level with related services, possessing both internal and external validity. The tool can be used with large samples

  15. Phenotypic robustness can increase phenotypic variability after non-genetic perturbations in gene regulatory circuits

    OpenAIRE

    Espinosa-Soto, C.; Martin, O. C.; Wagner, A

    2010-01-01

    Non-genetic perturbations, such as environmental change or developmental noise, can induce novel phenotypes. If an induced phenotype confers a fitness advantage, selection may promote its genetic stabilization. Non-genetic perturbations can thus initiate evolutionary innovation. Genetic variation that is not usually phenotypically visible may play an important role in this process. Populations under stabilizing selection on a phenotype that is robust to mutations can accumulate such variation...

  16. Two new mutations in a late infantile Tay-Sachs patient are both in exon 1 of the beta-hexosaminidase alpha subunit gene.

    OpenAIRE

    Harmon, D L; Gardner-Medwin, D; Stirling, J L

    1993-01-01

    We have identified two new point mutations in the beta-hexosaminidase alpha subunit (HEX A) gene in a non-Jewish Tay-Sachs disease patient with an unusual late infantile onset disease phenotype. The patient was a compound heterozygote with each allele of the HEX A gene containing a different mutation in exon 1. One of these is a T to C transition in the initiation codon, expected to produce no alpha subunit and therefore a classical infantile phenotype. The unusual clinical aspects and later ...

  17. Exploiting linkage disequilibrium in statistical modelling in quantitative genomics

    DEFF Research Database (Denmark)

    Wang, Lei

    the recently proposed antedependence models, which treat neighbouring marker effects as correlated; another approach involves use of haplotype block information derived using the program Beagle. The overall conclusion is that taking LD information into account in genomic prediction models potentially......Alleles at two loci are said to be in linkage disequilibrium (LD) when they are correlated or statistically dependent. Genomic prediction and gene mapping rely on the existence of LD between gentic markers and causul variants of complex traits. In the first part of the thesis, a novel method to...... quantify and visualize local variation in LD along chromosomes in describet, and applied to characterize LD patters at the local and genome-wide scale in three Danish pig breeds. In the second part, different ways of taking LD into account in genomic prediction models are studied. One approach is to use...

  18. Extensional hard linkages, eastern Gulf of Suez, Egypt

    Science.gov (United States)

    McClay, Ken; Khalil, Samir

    1998-06-01

    The Araba Abu Durba area on the eastern margin of the Gulf of Suez exhibits two superb outcrop examples of extensional hard linkages in a rift basin. Here, three large, domino-style, basement-cored, northeast-dipping fault blocks are formed by a series of major northwest-trending normal faults. These are offset by two north-northeast trending sinistral oblique-slip transfer faults that terminate in horsetail normal fault splays. The transfer faults do not extend across the entire rift basin. Detailed mapping and structural analysis show that they developed by breakage of initial low-strain relay ramps along reactivated north-northeast trending basement fabrics between overlapping northwest-trending normal fault segments. Paleostrain analysis of fault-slip indicators shows that both the normal and the sinistral oblique-slip transfer faults were formed synchronously in response to northeast-southwest extension, perpendicular to the main northwest rift trend.

  19. HIV testing and linkage to services for youth

    Directory of Open Access Journals (Sweden)

    Ann E Kurth

    2015-02-01

    Full Text Available Introduction: HIV testing is the portal to serostatus knowledge that can empower linkage to care for HIV treatment and HIV prevention. However, young people's access to HIV testing is uneven worldwide. The objective of this paper is to review the context and concerns faced by youth around HIV testing in low- as well as high-income country settings. Discussion: HIV testing is a critical entry point for primary and secondary prevention as well as care and treatment for young people including key populations of vulnerable youth. We provide a framework for thinking about the role of testing in the continuum of prevention and care for young people. Brief case study examples from Kenya and the US illustrate some of the common barriers and issues involved for young people. Conclusions: Young people worldwide need more routine access to HIV testing services that effectively address the developmental, socio-political and other issues faced by young women and men.

  20. Linkage of management decision to shareholder's value: EVA concept

    Directory of Open Access Journals (Sweden)

    Shrikant Krupasindhu Panigrahi

    2014-02-01

    Full Text Available In this paper, the author investigated the influence of management decisions like capital structure, dividend policies, remunerations, credit policy decisions and investment decisions on shareholder wealth maximization. To achieve the objective, portfolio theory, capital asset pricing model and modern financial theory providing evidence on the linkage between management decisions to shareholder’s value. Shareholders are only concerned about the value of shares of the company and the amount of return in the form of dividend paid. Thus in order to meet the demands of the shareholders of the company, managers needs to increase their abilities and skills to overcome the organizational goals. Thus the main goal of this paper is to discuss on the role of management decisions towards increasing shareholder’s wealth and meet organizational goals.

  1. Linkages between landscapes and human well-being

    DEFF Research Database (Denmark)

    Bieling, Claudia; Plieninger, Tobias; Pirker, Heidemarie;

    2014-01-01

    Human well-being is tightly linked to the natural environment. Although this notion is well-established, it remains difficult to assess how the biophysical features of a specific area contribute towards the well-being of the people attached to it. We explore this topic using the case of four areas...... in Germany and Austria by performing open, single-question interviews with 262 respondents. Data reveal an outstanding relevance of nonmaterial values. Linkages between landscapes and human well-being are tied to specific features of the material environment but, likewise, practices and experiences play...... to engage with their natural surroundings should be considered a strategy for fostering human well-being. ...

  2. The social ecology of health: leverage points and linkages.

    Science.gov (United States)

    Grzywacz, J G; Fuqua, J

    2000-01-01

    The authors demonstrate the usefulness of social ecology theory for improving the treatment and prevention of poor health. The social ecology of health, unlike the topics of previous triptychs in Behavioral Medicine, is a field without a clearly defined body of literature. We begin with an overview of the ecological perspective and ecological theory as outlined by Bronfenbrenner and colleagues, provide examples of how ecological concepts have been demonstrated to influence health, and discuss how these concepts can be used by health professionals. We present a heuristic model illustrating leverage points and linkages (i.e., socioeconomic status, family, work, and school), for health, and we conclude with a consideration of the benefits of social ecology to health professionals and a summary of the limitations of the ecological model.

  3. Damped Lyman-Alpha Galaxies

    CERN Document Server

    Turnshek, D A; Lane, W; Monier, E M; Nestor, D; Bergeron, J; Briggs, F; Smette, A

    2000-01-01

    Some results from an imaging program to identify low-redshift (0.09alpha (DLA) galaxies are presented. The standard paradigm that was widely accepted a decade ago, that DLA galaxies are the progenitors of luminous disk galaxies, is now being seriously challenged. The indisputable conclusion from imaging studies at low redshift is that the morphological types of DLA galaxies are mixed and that they span a range in luminosities and surface brightnesses.

  4. Crystalline anhydrous {alpha},{alpha}-trehalose (polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose: A calorimetric study

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Susana S. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: susanapinto@ist.utl.pt; Diogo, Herminio P. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: hdiogo@ist.utl.pt; Moura-Ramos, Joaquim J. [Centro de Quimica-Fisica Molecular, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: mouraramos@ist.utl.pt

    2006-09-15

    The mean values of the standard massic energy of combustion of crystalline anhydrous {alpha},{alpha}-trehalose (C{sub 12}H{sub 22}O{sub 11}, polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose (C{sub 12}H{sub 26}O{sub 13}) measured by static-bomb combustion calorimetry in oxygen, at the temperature T=298.15K, are {delta}{sub c}u{sup o}=-(16434.05+/-4.50)J.g{sup -1} and {delta}{sub c}u{sup o}=-(14816.05+/-3.52)J.g{sup -1}, respectively. The standard (p{sup o}=0.1MPa) molar enthalpy of formation of these compounds were derived from the corresponding standard molar enthalpies of combustion, respectively, {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 22}O{sub 11},cr)=-(2240.9+/-3.9)kJ.mol{sup -1}, and {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 26}O{sub 13},cr)=-(2832.6+/-3.6)kJ.mol{sup -1}. The values of the standard enthalpies of formation obtained in this work, together with data on enthalpies of solution at infinite dilution ({delta}{sub sol}H{sup {approx}}) for crystalline dihydrate and amorphous anhydrous trehalose, allow a better insight on the thermodynamic description of the trehalose system which can provide, together with the future research on the subject, a contribution for understanding the metabolism in several organisms, as well as the phase transition between the different polymorphs.

  5. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    NARCIS (Netherlands)

    Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have d

  6. Role of dystrophin in airway smooth muscle phenotype, contraction and lung function.

    Directory of Open Access Journals (Sweden)

    Pawan Sharma

    Full Text Available Dystrophin links the transmembrane dystrophin-glycoprotein complex to the actin cytoskeleton. We have shown that dystrophin-glycoprotein complex subunits are markers for airway smooth muscle phenotype maturation and together with caveolin-1, play an important role in calcium homeostasis. We tested if dystrophin affects phenotype maturation, tracheal contraction and lung physiology. We used dystrophin deficient Golden Retriever dogs (GRMD and mdx mice vs healthy control animals in our approach. We found significant reduction of contractile protein markers: smooth muscle myosin heavy chain (smMHC and calponin and reduced Ca2+ response to contractile agonist in dystrophin deficient cells. Immunocytochemistry revealed reduced stress fibers and number of smMHC positive cells in dystrophin-deficient cells, when compared to control. Immunoblot analysis of Akt1, GSK3β and mTOR phosphorylation further revealed that downstream PI3K signaling, which is essential for phenotype maturation, was suppressed in dystrophin deficient cell cultures. Tracheal rings from mdx mice showed significant reduction in the isometric contraction to methacholine (MCh when compared to genetic control BL10ScSnJ mice (wild-type. In vivo lung function studies using a small animal ventilator revealed a significant reduction in peak airway resistance induced by maximum concentrations of inhaled MCh in mdx mice, while there was no change in other lung function parameters. These data show that the lack of dystrophin is associated with a concomitant suppression of ASM cell phenotype maturation in vitro, ASM contraction ex vivo and lung function in vivo, indicating that a linkage between the DGC and the actin cytoskeleton via dystrophin is a determinant of the phenotype and functional properties of ASM.

  7. Prediction of disease and phenotype associations from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Stephanie N Lewis

    Full Text Available BACKGROUND: Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases. METHODOLOGY/PRINCIPAL FINDINGS: Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits. CONCLUSIONS/SIGNIFICANCE: The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

  8. The Cognitive Phenotype of Spina Bifida Meningomyelocele

    Science.gov (United States)

    Dennis, Maureen; Barnes, Marcia A.

    2010-01-01

    A cognitive phenotype is a product of both assets and deficits that specifies what individuals with spina bifida meningomyelocele (SBM) can and cannot do and why they can or cannot do it. In this article, we review the cognitive phenotype of SBM and describe the processing assets and deficits that cut within and across content domains, sensory…

  9. Association and linkage analysis of aluminum tolerance genes in maize.

    Directory of Open Access Journals (Sweden)

    Allison M Krill

    Full Text Available BACKGROUND: Aluminum (Al toxicity is a major worldwide constraint to crop productivity on acidic soils. Al becomes soluble at low pH, inhibiting root growth and severely reducing yields. Maize is an important staple food and commodity crop in acidic soil regions, especially in South America and Africa where these soils are very common. Al exclusion and intracellular tolerance have been suggested as two important mechanisms for Al tolerance in maize, but little is known about the underlying genetics. METHODOLOGY: An association panel of 282 diverse maize inbred lines and three F2 linkage populations with approximately 200 individuals each were used to study genetic variation in this complex trait. Al tolerance was measured as net root growth in nutrient solution under Al stress, which exhibited a wide range of variation between lines. Comparative and physiological genomics-based approaches were used to select 21 candidate genes for evaluation by association analysis. CONCLUSIONS: Six candidate genes had significant results from association analysis, but only four were confirmed by linkage analysis as putatively contributing to Al tolerance: Zea mays AltSB like (ZmASL, Zea mays aluminum-activated malate transporter2 (ALMT2, S-adenosyl-L-homocysteinase (SAHH, and Malic Enzyme (ME. These four candidate genes are high priority subjects for follow-up biochemical and physiological studies on the mechanisms of Al tolerance in maize. Immediately, elite haplotype-specific molecular markers can be developed for these four genes and used for efficient marker-assisted selection of superior alleles in Al tolerance maize breeding programs.

  10. Adjusting phenotypes by noise control.

    Directory of Open Access Journals (Sweden)

    Kyung H Kim

    2012-01-01

    Full Text Available Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.

  11. The autonomic phenotype of rumination.

    Science.gov (United States)

    Ottaviani, Cristina; Shapiro, David; Davydov, Dmitry M; Goldstein, Iris B; Mills, Paul J

    2009-06-01

    Recent studies suggest that ruminative thoughts may be mediators of the prolonged physiological effects of stress. We hypothesized that autonomic dysregulation plays a role in the relation between rumination and health. Rumination was induced by an anger-recall task in 45 healthy subjects. Heart rate variability (HRV), baroreflex sensitivity (BRS), and baroreflex effectiveness index (BEI) change scores were evaluated to obtain the autonomic phenotype of rumination. Personality traits and endothelial activation were examined for their relation to autonomic responses during rumination. Degree of endothelial activation was assessed by circulating soluble intercellular adhesion molecule-1 (sICAM-1). Vagal withdrawal during rumination was greater for women than men. Larger decreases in the high frequency component of HRV were associated with higher levels of anger-in, depression, and sICAM-1 levels. BRS reactivity was negatively related to trait anxiety. BEI reactivity was positively related to anger-in, hostility, anxiety, and depression. Lower BEI and BRS recovery were associated with lower social desirability and higher anger-out, anxiety, and depression. Findings suggest that the autonomic dysregulation that characterizes rumination plays a role in the relationships between personality and cardiovascular health. PMID:19272312

  12. [Hemoglobin Boumerdès alpha 2(37) (C2) Pro----Arg beta 2: a new variant of the alpha chain associated with hemoglobin S in an Algerian family].

    Science.gov (United States)

    Dahmane-Arbane, M; Blouquit, Y; Arous, N; Bardakdjian, J; Benamani, M; Riou, J; Benabadji, M; Rosa, J; Galacteros, F

    1987-01-01

    We report the first case of Hb Boumerdes, an alpha chain variant alpha 2(37) (C2) Pro----Arg beta 2, in an Algerian family. The propositus was also homozygous for the sickle cell gene. The abnormal hybrid Hb alpha 2Boum. beta 2S had an electrophoretic mobility on cellulose acetate pH 8.7 electrophoresis between those of Hb S and Hb A2. Its expression was about 16%. The alpha 2Boum. beta 2A fraction has a mobility between those of Hb F and Hb S. The effects of this mutation on Hb oxygen affinity and deoxy Hb S polymer formation were not studied. The propositus' sickle cell phenotype was benign. PMID:3438164

  13. Alpha voltaic batteries and methods thereof

    Science.gov (United States)

    Raffaelle, Ryne P. (Inventor); Jenkins, Phillip (Inventor); Wilt, David (Inventor); Scheiman, David (Inventor); Chubb, Donald (Inventor); Castro, Stephanie (Inventor)

    2011-01-01

    An alpha voltaic battery includes at least one layer of a semiconductor material comprising at least one p/n junction, at least one absorption and conversion layer on the at least one layer of semiconductor layer, and at least one alpha particle emitter. The absorption and conversion layer prevents at least a portion of alpha particles from the alpha particle emitter from damaging the p/n junction in the layer of semiconductor material. The absorption and conversion layer also converts at least a portion of energy from the alpha particles into electron-hole pairs for collection by the one p/n junction in the layer of semiconductor material.

  14. Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

    Directory of Open Access Journals (Sweden)

    Hong Liu

    Full Text Available BACKGROUND: As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH had remained unclear until recently when ABCB6 was reported as a causative gene of DUH. METHODOLOGY: We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation. RESULTS: Genome-wide linkage (assuming autosomal dominant inheritance mode and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them. CONCLUSION: Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

  15. Three novel quantitative trait loci for skin thickness in swine identified by linkage and genome-wide association studies.

    Science.gov (United States)

    Ai, Huashui; Xiao, Shijun; Zhang, Zhiyan; Yang, Bin; Li, Lin; Guo, Yuanmei; Lin, Guoshan; Ren, Jun; Huang, Lusheng

    2014-08-01

    Skin is the largest organ in the pig body and plays a key role in protecting the body against pathogens and excessive water loss. Deciphering the genetic basis of swine skin thickness would enrich our knowledge about the skin. To identify the loci for porcine skin thickness, we first performed a genome scan with 194 microsatellite markers in a White Duroc × Erhualian F2 intercross. We identified three genome-wide significant QTL on pig chromosomes (SSC) 4, 7 and 15 using linkage analysis. The most significant QTL was found on SSC7 with a small confidence interval of ~5 cM, explaining 23.9 percent of phenotypic variance. Further, we conducted a genome-wide association study (GWAS) using Illumina PorcineSNP60 Beadchips for the F2 pedigree and a population of Chinese Sutai pigs. We confirmed significant QTL in the F2 pedigree and replicated QTL on SSC15 in Chinese Sutai pigs. A meta-analysis of GWASs on both populations detected a genomic region associated with skin thickness on SSC4. GWAS results were generally consistent with QTL mapping. Identical-by-descent analysis defined QTL on SSC7 in a 683-kb region harboring an interesting candidate gene: HMGA1. On SSC15, the linkage disequilibrium analysis showed a haplotype block of 2.20 Mb that likely harbors the gene responsible for skin thickness. Our findings provide novel insights into the genetic basis of swine skin thickness, which would benefit further understanding of porcine skin function.

  16. A Picea abies linkage map based on SNP markers identifies QTLs for four aspects of resistance to Heterobasidion parviporum infection.

    Directory of Open Access Journals (Sweden)

    Mårten Lind

    Full Text Available A consensus linkage map of Picea abies, an economically important conifer, was constructed based on the segregation of 686 SNP markers in a F1 progeny population consisting of 247 individuals. The total length of 1889.2 cM covered 96.5% of the estimated genome length and comprised 12 large linkage groups, corresponding to the number of haploid P. abies chromosomes. The sizes of the groups (from 5.9 to 9.9% of the total map length correlated well with previous estimates of chromosome sizes (from 5.8 to 10.8% of total genome size. Any locus in the genome has a 97% probability to be within 10 cM from a mapped marker, which makes the map suited for QTL mapping. Infecting the progeny trees with the root rot pathogen Heterobasidion parviporum allowed for mapping of four different resistance traits: lesion length at the inoculation site, fungal spread within the sapwood, exclusion of the pathogen from the host after initial infection, and ability to prevent the infection from establishing at all. These four traits were associated with two, four, four and three QTL regions respectively of which none overlapped between the traits. Each QTL explained between 4.6 and 10.1% of the respective traits phenotypic variation. Although the QTL regions contain many more genes than the ones represented by the SNP markers, at least four markers within the confidence intervals originated from genes with known function in conifer defence; a leucoanthocyanidine reductase, which has previously been shown to upregulate during H. parviporum infection, and three intermediates of the lignification process; a hydroxycinnamoyl CoA shikimate/quinate hydroxycinnamoyltransferase, a 4-coumarate CoA ligase, and a R2R3-MYB transcription factor.

  17. An anxiety-like phenotype in mice selectively bred for aggression.

    Science.gov (United States)

    Nehrenberg, Derrick L; Rodriguiz, Ramona M; Cyr, Michel; Zhang, Xiaodong; Lauder, Jean M; Gariépy, Jean-Louis; Wetsel, William C

    2009-07-19

    Using selective bi-directional breeding procedures, two different lines of mice were developed. The NC900 line is highly reactive and attacks their social partners without provocation, whereas aggression in NC100 animals is uncommon in social environments. The enhanced reactivity of NC900 mice suggests that emotionality may have been selected with aggression. As certain forms of anxiety promote exaggerated defensive responses, we tested NC900 mice for the presence of an anxiety-like phenotype. In the open field, light-dark exploration, and zero maze tests, NC900 mice displayed anxiety-like responses. These animals were less responsive to the anxiolytic actions of diazepam in the zero maze than NC100 animals; diazepam also reduced the reactivity and attack behaviors of NC900 mice. The NC900 mice had reduced diazepam-sensitive GABA(A) receptor binding in brain regions associated with aggression and anxiety. Importantly, there was a selective reduction in levels of the GABA(A) receptor alpha(2) subunit protein in NC900 frontal cortex and amygdala; no changes in alpha(1) or gamma(2) subunit proteins were observed. These findings suggest that reductions in the alpha(2) subunit protein in selected brain regions may underlie the anxiety and aggressive phenotype of NC900 mice. Since anxiety and aggression are comorbid in certain psychiatric conditions, such as borderline personality and posttraumatic stress disorder, investigations with NC900 mice may provide new insights into basic mechanisms that underlie these and related psychiatric conditions. PMID:19428632

  18. Metabolomic phenotyping of af cloned pig model

    DEFF Research Database (Denmark)

    Clausen, Morten Rahr; Christensen, Kirstine Lykke; Hedemann, Mette Skou;

    2011-01-01

    Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes...... and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal...... outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n...

  19. Constraints on the evolution of phenotypic plasticity

    DEFF Research Database (Denmark)

    Murren, Courtney J; Auld, Josh R.; Callahan, Hilary S;

    2015-01-01

    costly. In addition, we examine opportunities to offset costs of phenotypes through ontogeny, amelioration of phenotypic costs across environments, and the condition-dependent hypothesis. We propose avenues of further inquiry in the limits of plasticity using new and classic methods of ecological......Phenotypic plasticity is ubiquitous and generally regarded as a key mechanism for enabling organisms to survive in the face of environmental change. Because no organism is infinitely or ideally plastic, theory suggests that there must be limits (for example, the lack of ability to produce...... an optimal trait) to the evolution of phenotypic plasticity, or that plasticity may have inherent significant costs. Yet numerous experimental studies have not detected widespread costs. Explicitly differentiating plasticity costs from phenotype costs, we re-evaluate fundamental questions of the limits...

  20. Phenotypic character gradient variation of Melia azedarach

    Institute of Scientific and Technical Information of China (English)

    CHENG Shiming; GU Wanchun

    2007-01-01

    Canonical Correlation Analysis (CCA) was applied on the research data of five geographical-climatic factors and 18 phenotypic characters of 729 trees of 24 populations of Melia azedarach distributed in China.The eigenvalue of the first canonical variable is 0.997 9 (significant at 0.01 level),accounting for 78% of all eigenvalues.A study on the principal component analysis (PCA) was done,taking the first canonical variable coordinate values as the phenotypic character gradient axes (PCGA).The isogram of the PCGA was drawn out with 0.2 contours,which showed a geographical model with a northeast-southwest variation trend of the phenotypic characters of M.azedarach.Meanwhile,the path analysis results show the direct and indirect effects of phenotypic characters with phenotypic character gradient values,which prove that the propagative organs,are steadily changing.