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Sample records for genetic linkage study

  1. Estimation of recombination frequency in genetic linkage studies.

    Science.gov (United States)

    Nordheim, E V; O'Malley, D M; Guries, R P

    1983-09-01

    A binomial-like model is developed that may be used in genetic linkage studies when data are generated by a testcross with parental phase unknown. Four methods of estimation for the recombination frequency are compared for data from a single group and also from several groups; these methods are maximum likelihood, two Bayesian procedures, and an ad hoc technique. The Bayes estimator using a noninformative prior usually has a lower mean squared error than the other estimators and because of this it is the recommended estimator. This estimator appears particularly useful for estimation of recombination frequencies indicative of weak linkage from samples of moderate size. Interval estimates corresponding to this estimator can be obtained numerically by discretizing the posterior distribution, thereby providing researchers with a range of plausible recombination values. Data from a linkage study on pitch pine are used as an example.

  2. Genetic linkage studies in non-epidermolytic palmoplantar keratoderma: evidence for heterogeneity.

    Science.gov (United States)

    Kelsell, D P; Stevens, H P; Ratnavel, R; Bryant, S P; Bishop, D T; Leigh, I M; Spurr, N K

    1995-06-01

    The palmoplantar keratodermas (PPK) are a group of skin diseases characterized by thickening of the skin of the palms and soles due to abnormal keratinization. We have performed linkage analysis on families affected with three distinct forms of non-epidermolytic PPK (NEPPK): focal, diffuse and punctate. Genetic heterogeneity was demonstrated, with focal NEPPK linked to the region on chromosome 17 harbouring the type I keratin cluster, diffuse NEPPK linked to the region on chromosome 12 containing the type II keratin cluster, and in the punctate NEPPK pedigrees, linkage was excluded to both of these keratin clusters. This study provides evidence for genetic differences between these forms of NEPPK and also between NEPPK and epidermolytic PPK (EPPK) in which mutations in keratin 9 have been demonstrated.

  3. 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.

  4. Constructing dense genetic linkage maps

    NARCIS (Netherlands)

    Jansen, J.; Jong, de A.G.; Ooijen, van J.W.

    2001-01-01

    This paper describes a novel combination of techniques for the construction of dense genetic linkage maps. The construction of such maps is hampered by the occurrence of even small proportions of typing errors. Simulated annealing is used to obtain the best map according to the optimality criterion:

  5. 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.

  6. Construction of a genetic linkage map of black gram, Vigna mungo (L.) Hepper, based on molecular markers and comparative studies.

    Science.gov (United States)

    Gupta, S K; Souframanien, J; Gopalakrishna, T

    2008-08-01

    A genetic linkage map of black gram, Vigna mungo (L.) Hepper, was constructed with 428 molecular markers using an F9 recombinant inbred population of 104 individuals. The population was derived from an inter-subspecific cross between a black gram cultivar, TU94-2, and a wild genotype, V. mungo var. silvestris. The linkage analysis at a LOD score of 5.0 distributed all 428 markers (254 AFLP, 47 SSR, 86 RAPD, and 41 ISSR) into 11 linkage groups. The map spanned a total distance of 865.1 cM with an average marker density of 2 cM. The largest linkage group spanned 115 cM and the smallest linkage group was of 44.9 cM. The number of markers per linkage group ranged from 11 to 86 and the average distance between markers varied from 1.1 to 5.6 cM. Comparison of the map with other published azuki bean and black gram maps showed high colinearity of markers, with some inversions. The current map is the most saturated map for black gram to date and will provide a useful tool for identification of QTLs and for marker-assisted selection of agronomically important characters in black gram.

  7. Genetic linkage studies in autosomal dominant ataxia families with an MJD phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, I.; Lopes-Cendes, I.; Paciel, P. [McGill Univ., Montreal (Canada)] [and others

    1994-09-01

    Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration which was originally described in patients originating from the Portuguese islands of the Azores. The first non-Portuguese kindred was described in 1979 and was an American black family originating from North Carolina. Since then the number of pedigrees of non-Azorean, non-Portuguese origin has increased with families being reported from other European countries, as well as Brazil, Japan, India, The United States and Australia. The autosomal dominant ataxias are a clinically and genetically heterogeneous group of disorders. To date, genetic analysis of families with autosomal dominant ataxias has permitted the identification of four loci, the SCA1 (spinocerebellar ataxia type 1) locus on chromosome 6p, the SCA2 locus on chromosome 12q, a third locus on chromosome 14q, the MJD/SCA3 and, more recently, the DRPLA (Dentatorubral-pallidoluysian atrophy) locus on chromosome 12p. We ascertained a total of 181 individuals with 60 affected from eight Indian, two Brazilian and one Sicilian-American family; all of them have received the clinical diagnosis of MJD. Recently, we have begun molecular genetic studies in these families in order to test these four candidate regions. The SCA1 mutation and the DRPLA mutation has been found to be an expansion of a CAG repeat. Direct analysis of the SCA1 and DRPLA expansion has been performed in all families and no expansion was found in the affected individuals. We are now running flanking markers for the SCA2 and MJD/SCA3 loci. These results will also be presented.

  8. Obstetric prognosis in sisters of preeclamptic women – implications for genetic linkage studies

    Directory of Open Access Journals (Sweden)

    Heinonen Seppo

    2003-02-01

    Full Text Available Abstract Background To investigate obstetric prognosis in sisters of preeclamptic women. Methods We identified consecutive 635 sib pairs from the Birth Registry data of Kuopio University Hospital who had their first delivery between January 1989 and December 1999 in our institution. Of these, in 530 pairs both sisters had non-preeclamptic pregnancies (the reference group, in 63 pairs one of the sisters had preeclampsia and the unaffected sisters were studied (study group I. In 42 pairs both sister's first delivery was affected (study group II. Pregnancy outcome measures in these groups were compared. Results Unaffected sisters of the index patients had uncompromised fetal growth in their pregnancies, and overall, as good obstetric outcomes as in the reference group. The data on affected sisters of the index patients showed an increased prematurity rate, and increased incidences of low birth weight and small-for-gestational age infants, as expected. Conclusion Unaffected sisters of the index patients had no signs of utero-placental insufficiency and they were at low risk with regard to adverse obstetric outcome, whereas affected sisters were high-risk. Clinically, affected versus unaffected status appears to be clear-cut in first-degree relatives regardless of their genetic susceptibility and unaffected sisters do not need special antepartum surveillance.

  9. Clinical correlates and genetic linkage of social and communication difficulties in families with obsessive-compulsive disorder: Results from the OCD Collaborative Genetics Study.

    Science.gov (United States)

    Samuels, Jack; Shugart, Yin Yao; Wang, Ying; Grados, Marco A; Bienvenu, O Joseph; Pinto, Anthony; Rauch, Scott L; Greenberg, Benjamin D; Knowles, James A; Fyer, Abby J; Piacentini, John; Pauls, David L; Cullen, Bernadette; Rasmussen, Steven A; Stewart, S Evelyn; Geller, Dan A; Maher, Brion S; Goes, Fernando S; Murphy, Dennis L; McCracken, James T; Riddle, Mark A; Nestadt, Gerald

    2014-06-01

    Some individuals with obsessive-compulsive disorder (OCD) have autistic-like traits, including deficits in social and communication behaviors (pragmatics). The objective of this study was to determine if pragmatic impairment aggregates in OCD families and discriminates a clinically and genetically distinct subtype of OCD. We conducted clinical examinations on, and collected DNA samples from, 706 individuals with OCD in 221 multiply affected OCD families. Using the Pragmatic Rating Scale (PRS), we compared the prevalence of pragmatic impairment in OCD-affected relatives of probands with and without pragmatic impairment. We also compared clinical features of OCD-affected individuals in families having at least one, versus no, individual with pragmatic impairment, and assessed for linkage to OCD in the two groups of families. The odds of pragmatic impairment were substantially greater in OCD-affected relatives of probands with pragmatic impairment. Individuals in high-PRS families had greater odds of separation anxiety disorder and social phobia, and a greater number of schizotypal personality traits. In high-PRS families, there was suggestive linkage to OCD on chromosome 12 at marker D12S1064 and on chromosome X at marker DXS7132 whereas, in low-PRS families, there was suggestive linkage to chromosome 3 at marker D3S2398. Pragmatic impairment aggregates in OCD families. Separation anxiety disorder, social phobia, and schizotypal personality traits are part of a clinical spectrum associated with pragmatic impairment in these families. Specific regions of chromosomes 12 and X are linked to OCD in high-PRS families. Thus, pragmatic impairment may distinguish a clinically and genetically homogeneous subtype of OCD. © 2014 Wiley Periodicals, Inc.

  10. Methods for genetic linkage analysis using trisomies

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-02-01

    Certain genetic disorders are rare in the general population, but more common in individuals with specific trisomies. Examples of this include leukemia and duodenal atresia in trisomy 21. This paper presents a linkage analysis method for using trisomic individuals to map genes for such traits. It is based on a very general gene-specific dosage model that posits that the trait is caused by specific effects of different alleles at one or a few loci and that duplicate copies of {open_quotes}susceptibility{close_quotes} alleles inherited from the nondisjoining parent give increased likelihood of having the trait. Our mapping method is similar to identity-by-descent-based mapping methods using affected relative pairs and also to methods for mapping recessive traits using inbred individuals by looking for markers with greater than expected homozygosity by descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected homozygosity in the chromosomes inherited from the nondisjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the trait gene, a confidence interval for that distance, and methods for computing power and sample sizes. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers and how to test candidate genes. 20 refs., 5 figs., 1 tab.

  11. 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

  12. A genetic linkage map for Tribolium confusum based on random amplified polymorphic DNAs and recombinant inbred lines.

    Science.gov (United States)

    Yezerski, A; Stevens, L; Ametrano, J

    2003-10-01

    Tribolium beetles provide an excellent and easily manipulated model system for the study of genetics. However, despite significant increases in the availability of molecular markers for the study of genetics in recent years, a significant genetic linkage map for these beetles remains undeveloped. We present the first molecular genetic linkage map for Tribolium confusum using random amplified polymorphic DNA markers. The linkage map contains 137 loci mapped on to eight linkage groups totaling 968.5 cM.

  13. Methods for genetic linkage analysis using trisomies

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

    Certain genetic disorders (e.g. congenital cataracts, duodenal atresia) are rare in the general population, but more common in people with Down`s syndrome. We present a method for using individuals with trisomy 21 to map genes for such traits. Our methods are analogous to methods for mapping autosomal dominant traits using affected relative pairs by looking for markers with greater than expected identity-by-descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected reduction to homozygosity in the chromosomes inherited form the non-disjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the gene, a confidence interval for that distance, and methods for computing power and sample sizes. The methods are described in the context of gene-dosage model for the etiology of the disorder, but can be extended to other models. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers, how to test candidate genes, and how to handle the effect of reduced recombination associated with maternal meiosis I non-disjunction.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lopes-Cendes, I. [Montreal General Hospital (Canada); Mulley, J.C. [Alelaide Children`s Hospital (Canada); Andermann, E. [Montreal Neurological Institute and Hospital, Quebec (Canada)] [and others

    1994-09-01

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

  15. [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.

  16. Preliminary genetic linkage map of Indian major carp, Labeo rohita (Hamilton 1822) based on microsatellite markers

    Indian Academy of Sciences (India)

    L. Sahoo; A. Patel; B. P. Sahu; S. Mitra; P. K. Meher; K. D. Mahapatra; S. K. Dash; P. Jayasankar; P. Das

    2015-06-01

    Linkage map with wide marker coverage is an essential resource for genetic improvement study for any species. Sex-averaged genetic linkage map of Labeo rohita, popularly known as ‘rohu’, widely cultured in the Indian subcontinent, was developed by placing 68 microsatellite markers generated by a simplified method. The parents and their F1 progeny (92 individuals) were used as segregating populations. The genetic linkage map spans a sex-averaged total length of 1462.2 cM, in 25 linkage groups. The genome length of rohu was estimated to be 3087.9 cM. This genetic linkage map may facilitate systematic searches of the genome to identify genes associated with commercially important characters and marker-assisted selection programmes of this species.

  17. Prioritizing tiger conservation through landscape genetics and habitat linkages.

    Science.gov (United States)

    Yumnam, Bibek; Jhala, Yadvendradev V; Qureshi, Qamar; Maldonado, Jesus E; Gopal, Rajesh; Saini, Swati; Srinivas, Y; Fleischer, Robert C

    2014-01-01

    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 provide legal status

  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. A genetic linkage map and comparative mapping of the prairie vole (Microtus ochrogaster genome

    Directory of Open Access Journals (Sweden)

    Young Larry J

    2011-07-01

    Full Text Available Abstract Background The prairie vole (Microtus ochrogaster is an emerging rodent model for investigating the genetics, evolution and molecular mechanisms of social behavior. Though a karyotype for the prairie vole has been reported and low-resolution comparative cytogenetic analyses have been done in this species, other basic genetic resources for this species, such as a genetic linkage map, are lacking. Results Here we report the construction of a genome-wide linkage map of the prairie vole. The linkage map consists of 406 markers that are spaced on average every 7 Mb and span an estimated ~90% of the genome. The sex average length of the linkage map is 1707 cM, which, like other Muroid rodent linkage maps, is on the lower end of the length distribution of linkage maps reported to date for placental mammals. Linkage groups were assigned to 19 out of the 26 prairie vole autosomes as well as the X chromosome. Comparative analyses of the prairie vole linkage map based on the location of 387 Type I markers identified 61 large blocks of synteny with the mouse genome. In addition, the results of the comparative analyses revealed a potential elevated rate of inversions in the prairie vole lineage compared to the laboratory mouse and rat. Conclusions A genetic linkage map of the prairie vole has been constructed and represents the fourth genome-wide high-resolution linkage map reported for Muroid rodents and the first for a member of the Arvicolinae sub-family. This resource will advance studies designed to dissect the genetic basis of a variety of social behaviors and other traits in the prairie vole as well as our understanding of genome evolution in the genus Microtus.

  20. SSR and EST-SSR-based genetic linkage map of cassava (Manihot esculenta Crantz).

    Science.gov (United States)

    Sraphet, Supajit; Boonchanawiwat, Athipong; Thanyasiriwat, Thanwanit; Boonseng, Opas; Tabata, Satoshi; Sasamoto, Shigemi; Shirasawa, Kenta; Isobe, Sachiko; Lightfoot, David A; Tangphatsornruang, Sithichoke; Triwitayakorn, Kanokporn

    2011-04-01

    Simple sequence repeat (SSR) markers provide a powerful tool for genetic linkage map construction that can be applied for identification of quantitative trait loci (QTL). In this study, a total of 640 new SSR markers were developed from an enriched genomic DNA library of the cassava variety 'Huay Bong 60' and 1,500 novel expressed sequence tag-simple sequence repeat (EST-SSR) loci were developed from the Genbank database. To construct a genetic linkage map of cassava, a 100 F(1) line mapping population was developed from the cross Huay Bong 60 by 'Hanatee'. Polymorphism screening between the parental lines revealed that 199 SSRs and 168 EST-SSRs were identified as novel polymorphic markers. Combining with previously developed SSRs, we report a linkage map consisted of 510 markers encompassing 1,420.3 cM, distributed on 23 linkage groups with a mean distance between markers of 4.54 cM. Comparison analysis of the SSR order on the cassava linkage map and the cassava genome sequences allowed us to locate 284 scaffolds on the genetic map. Although the number of linkage groups reported here revealed that this F(1) genetic linkage map is not yet a saturated map, it encompassed around 88% of the cassava genome indicating that the map was almost complete. Therefore, sufficient markers now exist to encompass most of the genomes and efficiently map traits in cassava.

  1. 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.

  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.

  3. Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study

    Science.gov (United States)

    Seshadri, Sudha; DeStefano, Anita L; Au, Rhoda; Massaro, Joseph M; Beiser, Alexa S; Kelly-Hayes, Margaret; Kase, Carlos S; D'Agostino, Ralph B; DeCarli, Charles; Atwood, Larry D; Wolf, Philip A

    2007-01-01

    Background Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. Methods A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999–2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. Results The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10-6) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10-8) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously

  4. Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study

    OpenAIRE

    2007-01-01

    Abstract Background Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. Methods A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and ...

  5. 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.

  6. 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

  7. 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.

  8. Genetic linkage mapping in fungi: current state, applications, and future trends.

    Science.gov (United States)

    Foulongne-Oriol, Marie

    2012-08-01

    Genetic mapping is a basic tool for eukaryotic genomic research. Linkage maps provide insights into genome organization and can be used for genetic studies of traits of interest. A genetic linkage map is a suitable support for the anchoring of whole genome sequences. It allows the localization of genes of interest or quantitative trait loci (QTL) and map-based cloning. While genetic mapping has been extensively used in plant or animal models, this discipline is more recent in fungi. The present article reviews the current status of genetic linkage map research in fungal species. The process of linkage mapping is detailed, from the development of mapping populations to the construction of the final linkage map, and illustrated based on practical examples. The range of specific applications in fungi is browsed, such as the mapping of virulence genes in pathogenic species or the mapping of agronomically relevant QTL in cultivated edible mushrooms. Future prospects are finally discussed in the context of the most recent advances in molecular techniques and the release of numerous fungal genome sequences.

  9. Genetic Linkage Map of the Edible Basidiomycete Pleurotus ostreatus

    Science.gov (United States)

    Larraya, Luis M.; Pérez, Gúmer; Ritter, Enrique; Pisabarro, Antonio G.; Ramírez, Lucía

    2000-01-01

    We have constructed a genetic linkage map of the edible basidiomycete Pleurotus ostreatus (var. Florida). The map is based on the segregation of 178 random amplified polymorphic DNA and 23 restriction fragment length polymorphism markers; four hydrophobin, two laccase, and two manganese peroxidase genes; both mating type loci; one isozyme locus (est1); the rRNA gene sequence; and a repetitive DNA sequence in a population of 80 sibling monokaryons. The map identifies 11 linkage groups corresponding to the chromosomes of P. ostreatus, and it has a total length of 1,000.7 centimorgans (cM) with an average of 35.1 kbp/cM. The map shows a high correlation (0.76) between physical and genetic chromosome sizes. The number of crossovers observed per chromosome per individual cell is 0.89. This map covers nearly the whole genome of P. ostreatus. PMID:11097904

  10. Dissecting the Genetics of Complex Inheritance: Linkage Disequilibrium Mapping Provides Insight into Crohn Disease

    OpenAIRE

    Elding, Heather; Lau, Winston; Swallow, Dallas M.; Maniatis, Nikolas

    2011-01-01

    Family studies for Crohn disease (CD) report extensive linkage on chromosome 16q and pinpoint NOD2 as a possible causative locus. However, linkage is also observed in families that do not bear the most frequent NOD2 causative mutations, but no other signals on 16q have been found so far in published genome-wide association studies. Our aim is to identify this missing genetic contribution. We apply a powerful genetic mapping approach to the Wellcome Trust Case-Control Consortium and the Nation...

  11. Identifying plausible genetic models based on association and linkage results: application to type 2 diabetes.

    Science.gov (United States)

    Guan, Weihua; Boehnke, Michael; Pluzhnikov, Anna; Cox, Nancy J; Scott, Laura J

    2012-12-01

    When planning resequencing studies for complex diseases, previous association and linkage studies can constrain the range of plausible genetic models for a given locus. Here, we explore the combinations of causal risk allele frequency (RAFC ) and genotype relative risk (GRRC ) consistent with no or limited evidence for affected sibling pair (ASP) linkage and strong evidence for case-control association. We find that significant evidence for case-control association combined with no or moderate evidence for ASP linkage can define a lower bound for the plausible RAFC . Using data from large type 2 diabetes (T2D) linkage and genome-wide association study meta-analyses, we find that under reasonable model assumptions, 23 of 36 autosomal T2D risk loci are unlikely to be due to causal variants with combined RAFC < 0.005, and four of the 23 are unlikely to be due to causal variants with combined RAFC < 0.05.

  12. 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

  13. Near-saturated and complete genetic linkage map of black spruce (Picea mariana).

    Science.gov (United States)

    Kang, Bum-Yong; Mann, Ishminder K; Major, John E; Rajora, Om P

    2010-09-24

    Genetic maps provide an important genomic resource for understanding genome organization and evolution, comparative genomics, mapping genes and quantitative trait loci, and associating genomic segments with phenotypic traits. Spruce (Picea) genomics work is quite challenging, mainly because of extremely large size and highly repetitive nature of its genome, unsequenced and poorly understood genome, and the general lack of advanced-generation pedigrees. Our goal was to construct a high-density genetic linkage map of black spruce (Picea mariana, 2n = 24), which is a predominant, transcontinental species of the North American boreal and temperate forests, with high ecological and economic importance. We have developed a near-saturated and complete genetic linkage map of black spruce using a three-generation outbred pedigree and amplified fragment length polymorphism (AFLP), selectively amplified microsatellite polymorphic loci (SAMPL), expressed sequence tag polymorphism (ESTP), and microsatellite (mostly cDNA based) markers. Maternal, paternal, and consensus genetic linkage maps were constructed. The maternal, paternal, and consensus maps in our study consistently coalesced into 12 linkage groups, corresponding to the haploid chromosome number (1n = 1x = 12) of 12 in the genus Picea. The maternal map had 816 and the paternal map 743 markers distributed over 12 linkage groups each. The consensus map consisted of 1,111 markers distributed over 12 linkage groups, and covered almost the entire (> 97%) black spruce genome. The mapped markers included 809 AFLPs, 255 SAMPL, 42 microsatellites, and 5 ESTPs. Total estimated length of the genetic map was 1,770 cM, with an average of one marker every 1.6 cM. The maternal, paternal and consensus genetic maps aligned almost perfectly. We have constructed the first high density to near-saturated genetic linkage map of black spruce, with greater than 97% genome coverage. Also, this is the first genetic map based on a three

  14. Near-saturated and complete genetic linkage map of black spruce (Picea mariana

    Directory of Open Access Journals (Sweden)

    Mann Ishminder K

    2010-09-01

    Full Text Available Abstract Background Genetic maps provide an important genomic resource for understanding genome organization and evolution, comparative genomics, mapping genes and quantitative trait loci, and associating genomic segments with phenotypic traits. Spruce (Picea genomics work is quite challenging, mainly because of extremely large size and highly repetitive nature of its genome, unsequenced and poorly understood genome, and the general lack of advanced-generation pedigrees. Our goal was to construct a high-density genetic linkage map of black spruce (Picea mariana, 2n = 24, which is a predominant, transcontinental species of the North American boreal and temperate forests, with high ecological and economic importance. Results We have developed a near-saturated and complete genetic linkage map of black spruce using a three-generation outbred pedigree and amplified fragment length polymorphism (AFLP, selectively amplified microsatellite polymorphic loci (SAMPL, expressed sequence tag polymorphism (ESTP, and microsatellite (mostly cDNA based markers. Maternal, paternal, and consensus genetic linkage maps were constructed. The maternal, paternal, and consensus maps in our study consistently coalesced into 12 linkage groups, corresponding to the haploid chromosome number (1n = 1x = 12 of 12 in the genus Picea. The maternal map had 816 and the paternal map 743 markers distributed over 12 linkage groups each. The consensus map consisted of 1,111 markers distributed over 12 linkage groups, and covered almost the entire (> 97% black spruce genome. The mapped markers included 809 AFLPs, 255 SAMPL, 42 microsatellites, and 5 ESTPs. Total estimated length of the genetic map was 1,770 cM, with an average of one marker every 1.6 cM. The maternal, paternal and consensus genetic maps aligned almost perfectly. Conclusion We have constructed the first high density to near-saturated genetic linkage map of black spruce, with greater than 97% genome coverage. Also, this

  15. Annotated genetic linkage maps of Pinus pinaster Ait. from a Central Spain population using microsatellite and gene based markers

    Directory of Open Access Journals (Sweden)

    de Miguel Marina

    2012-10-01

    Full Text Available Abstract Background Pinus pinaster Ait. is a major resin producing species in Spain. Genetic linkage mapping can facilitate marker-assisted selection (MAS through the identification of Quantitative Trait Loci and selection of allelic variants of interest in breeding populations. In this study, we report annotated genetic linkage maps for two individuals (C14 and C15 belonging to a breeding program aiming to increase resin production. We use different types of DNA markers, including last-generation molecular markers. Results We obtained 13 and 14 linkage groups for C14 and C15 maps, respectively. A total of 211 and 215 markers were positioned on each map and estimated genome length was between 1,870 and 2,166 cM respectively, which represents near 65% of genome coverage. Comparative mapping with previously developed genetic linkage maps for P. pinaster based on about 60 common markers enabled aligning linkage groups to this reference map. The comparison of our annotated linkage maps and linkage maps reporting QTL information revealed 11 annotated SNPs in candidate genes that co-localized with previously reported QTLs for wood properties and water use efficiency. Conclusions This study provides genetic linkage maps from a Spanish population that shows high levels of genetic divergence with French populations from which segregating progenies have been previously mapped. These genetic maps will be of interest to construct a reliable consensus linkage map for the species. The importance of developing functional genetic linkage maps is highlighted, especially when working with breeding populations for its future application in MAS for traits of interest.

  16. A genetic linkage map of Venturia inaequalis, the causal agent of apple scab

    Directory of Open Access Journals (Sweden)

    Harvey Nick G

    2009-08-01

    Full Text Available Abstract Background Venturia inaequalis is an economically-important disease of apple causing annual epidemics of scab worldwide. The pathogen is a heterothallic ascomycete with an annual cycle of sexual reproduction on infected apple leaf litter, followed by several cycles of asexual reproduction during the apple growing season. Current disease control is achieved mainly through scheduled applications of fungicides. Genetic linkage maps are essential for studying genome structure and organisation, and are a valuable tool for identifying the location of genes controlling important traits of interest such as avirulence, host specificity and mating type in V. inaequalis. In this study, we performed a wide cross under in vitro conditions between an isolate of V. inaequalis from China and one from the UK to obtain a genetically diverse mapping population of ascospore progeny isolates and produced a map using AFLP and microsatellite (SSR markers. Findings Eighty-three progeny were obtained from the cross between isolates C0154 (China × 01/213 (UK. The progeny was screened with 18 AFLP primer combinations and 31 SSRs, and scored for the mating type locus MAT. A linkage map was constructed consisting of 294 markers (283 AFLPs, ten SSRs and the MAT locus, spanning eleven linkage groups and with a total map length of 1106 cM. The length of individual linkage groups ranged from 30.4 cM (Vi-11 to 166 cM (Vi-1. The number of molecular markers per linkage group ranged from 7 on Vi-11 to 48 on Vi-3; the average distance between two loci within each group varied from 2.4 cM (Vi-4 to 7.5 cM (Vi-9. The maximum map length between two markers within a linkage group was 15.8 cM. The MAT locus was mapped to a small linkage group and was tightly linked to two AFLP markers. The map presented is over four times longer than the previously published map of V. inaequalis which had a total genetic distance of just 270 cM. Conclusion A genetic linkage map is an important

  17. Preliminary genetic linkage maps of Chinese herb Dendrobium nobile and D. moniliforme

    Indian Academy of Sciences (India)

    Shangguo Feng; Hongyan Zhao; Jiangjie Lu; Junjun Liu; Bo Shen; Huizhong Wang

    2013-08-01

    Dendrobium is an endangered genus in the orchid family with medicinal and horticultural value. Two preliminary genetic linkage maps were constructed using 90 F1 progeny individuals derived from an interspecific cross between D. nobile and D. moniliforme (both, $2n = 38$), using random amplified polymorphic DNA (RAPD) and intersimple sequence repeat (ISSR). A total of 286 RAPD loci and 68 ISSR loci were identified and used for genetic linkage analysis. Maps were constructed by double pseudo-testcross mapping strategy using the software Mapmaker/EXP ver. 3.0, and Kosambi map distances were constructed using a LOD score ≥4 and a recombination threshold of 0.4. The resulting frame map of D. nobile was 1474 cM in total length with 116 loci distributed in 15 linkage groups; and the D. moniliforme linkage map had 117 loci placed in 16 linkage groups spanning 1326.5 cM. Both maps showed 76.91% and 73.59% genome coverage for D. nobile and D. moniliforme, respectively. These primary maps provide an important basis for genetic studies and further medicinal and horticultural traits mapping and marker-assisted selection in Dendrobium breeding programmes.

  18. Genetic linkage mapping in an F2 perennial ryegrass population using DArT markers

    DEFF Research Database (Denmark)

    Tomaszewski, Céline; Byrne, Stephen; Foito, Alexandra;

    2012-01-01

    T markers, and a DArT array has recently been developed for the Lolium-Festuca complex. In this study, we report the first use of the DArTFest array to generate a genetic linkage map based on 326 markers in a Lolium perenne F2 population, consisting of 325 genotypes. For proof of concept, the map was used...

  19. Genetic variation and linkage disequilibrium in Bacillus anthracis.

    Science.gov (United States)

    Zwick, Michael E; Thomason, Maureen Kiley; Chen, Peter E; Johnson, Henry R; Sozhamannan, Shanmuga; Mateczun, Alfred; Read, Timothy D

    2011-01-01

    We performed whole-genome amplification followed by hybridization of custom-designed resequencing arrays to resequence 303 kb of genomic sequence from a worldwide panel of 39 Bacillus anthracis strains. We used an efficient algorithm contained within a custom software program, UniqueMER, to identify and mask repetitive sequences on the resequencing array to reduce false-positive identification of genetic variation, which can arise from cross-hybridization. We discovered a total of 240 single nucleotide variants (SNVs) and showed that B. anthracis strains have an average of 2.25 differences per 10,000 bases in the region we resequenced. Common SNVs in this region are found to be in complete linkage disequilibrium. These patterns of variation suggest there has been little if any historical recombination among B. anthracis strains since the origin of the pathogen. This pattern of common genetic variation suggests a framework for recognizing new or genetically engineered strains.

  20. Dissecting the genetics of complex inheritance: linkage disequilibrium mapping provides insight into Crohn disease.

    Science.gov (United States)

    Elding, Heather; Lau, Winston; Swallow, Dallas M; Maniatis, Nikolas

    2011-12-09

    Family studies for Crohn disease (CD) report extensive linkage on chromosome 16q and pinpoint NOD2 as a possible causative locus. However, linkage is also observed in families that do not bear the most frequent NOD2 causative mutations, but no other signals on 16q have been found so far in published genome-wide association studies. Our aim is to identify this missing genetic contribution. We apply a powerful genetic mapping approach to the Wellcome Trust Case-Control Consortium and the National Institute of Diabetes and Digestive and Kidney Diseases genome-wide association data on CD. This method takes into account the underlying structure of linkage disequilibrium (LD) by using genetic distances from LD maps and provides a location for the causal agent. We find genetic heterogeneity within the NOD2 locus and also show an independent and unsuspected involvement of the neighboring gene, CYLD. We find associations with the IRF8 region and the region containing CDH1 and CDH3, as well as substantial phenotypic and genetic heterogeneity for CD itself. The genes are known to be involved in inflammation and immune dysregulation. These findings provide insight into the genetics of CD and suggest promising directions for understanding disease heterogeneity. The application of this method thus paves the way for understanding complex inheritance in general, leading to the dissection of different pathways and ultimately, personalized treatment. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  1. A second-generation anchored genetic linkage map of the tammar wallaby (Macropus eugenii

    Directory of Open Access Journals (Sweden)

    Patel Hardip R

    2011-08-01

    Full Text Available Abstract Background The tammar wallaby, Macropus eugenii, a small kangaroo used for decades for studies of reproduction and metabolism, is the model Australian marsupial for genome sequencing and genetic investigations. The production of a more comprehensive cytogenetically-anchored genetic linkage map will significantly contribute to the deciphering of the tammar wallaby genome. It has great value as a resource to identify novel genes and for comparative studies, and is vital for the ongoing genome sequence assembly and gene ordering in this species. Results A second-generation anchored tammar wallaby genetic linkage map has been constructed based on a total of 148 loci. The linkage map contains the original 64 loci included in the first-generation map, plus an additional 84 microsatellite loci that were chosen specifically to increase coverage and assist with the anchoring and orientation of linkage groups to chromosomes. These additional loci were derived from (a sequenced BAC clones that had been previously mapped to tammar wallaby chromosomes by fluorescence in situ hybridization (FISH, (b End sequence from BACs subsequently FISH-mapped to tammar wallaby chromosomes, and (c tammar wallaby genes orthologous to opossum genes predicted to fill gaps in the tammar wallaby linkage map as well as three X-linked markers from a published study. Based on these 148 loci, eight linkage groups were formed. These linkage groups were assigned (via FISH-mapped markers to all seven autosomes and the X chromosome. The sex-pooled map size is 1402.4 cM, which is estimated to provide 82.6% total coverage of the genome, with an average interval distance of 10.9 cM between adjacent markers. The overall ratio of female/male map length is 0.84, which is comparable to the ratio of 0.78 obtained for the first-generation map. Conclusions Construction of this second-generation genetic linkage map is a significant step towards complete coverage of the tammar wallaby

  2. An EST-derived SNP and SSR genetic linkage map of cassava (Manihot esculenta Crantz).

    Science.gov (United States)

    Rabbi, Ismail Yusuf; Kulembeka, Heneriko Philbert; Masumba, Esther; Marri, Pradeep Reddy; Ferguson, Morag

    2012-07-01

    Cassava (Manihot esculenta Crantz) is one of the most important food security crops in the tropics and increasingly being adopted for agro-industrial processing. Genetic improvement of cassava can be enhanced through marker-assisted breeding. For this, appropriate genomic tools are required to dissect the genetic architecture of economically important traits. Here, a genome-wide SNP-based genetic map of cassava anchored in SSRs is presented. An outbreeder full-sib (F1) family was genotyped on two independent SNP assay platforms: an array of 1,536 SNPs on Illumina's GoldenGate platform was used to genotype a first batch of 60 F1. Of the 1,358 successfully converted SNPs, 600 which were polymorphic in at least one of the parents and was subsequently converted to KBiosciences' KASPar assay platform for genotyping 70 additional F1. High-precision genotyping of 163 informative SSRs using capillary electrophoresis was also carried out. Linkage analysis resulted in a final linkage map of 1,837 centi-Morgans (cM) containing 568 markers (434 SNPs and 134 SSRs) distributed across 19 linkage groups. The average distance between adjacent markers was 3.4 cM. About 94.2% of the mapped SNPs and SSRs have also been localized on scaffolds of version 4.1 assembly of the cassava draft genome sequence. This more saturated genetic linkage map of cassava that combines SSR and SNP markers should find several applications in the improvement of cassava including aligning scaffolds of the cassava genome sequence, genetic analyses of important agro-morphological traits, studying the linkage disequilibrium landscape and comparative genomics.

  3. 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...

  4. Construction of Genetic Linkage Map Based on SSR Markers in Peanut(Arachis hypogaea L.)

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Molecular genetic maps of crop species can be used in a variety of ways in breeding and genomic research such as identification and mapping of genes and quantitative trait loci (QTLs) for morphological, physiological and economic traits of crop species. However, a comprehensive genetic linkage map for cultivated peanut has not yet been developed due to the extremely low frequency of DNA polymorphism in cultivated peanut. In this study, 142 recombinant inbred lines (RILs) derived from a cross between Yueyou 13 and Zhenzhuhei were used as mapping population in peanut (Arachis hypogaea L.). A total 652 pairs of genomic-SSR primer and 392 pairs of EST-SSR primer were used to detect the polymorphisms between the two parents. 141 SSR primer pairs, 127 genomic-SSR and 14 EST-SSR ones, which can be used to detect polymorphisms between the two parents, were selected to analyze the RILs population. Thus, a linkage genetic map which consists of 131 SSR loci in 20 linkage groups, with a coverage of 679 cM and an average of 6.12 cM of inter-maker distance was constructed. The putative functions of 12 EST-SSR markers located on the map were analyzed. Eleven showed homology to gene sequences deposited in GenBank. This is the first report of construction of a comprehensive genetic map with SSR markers in peanut (Arachis hypogaea L.). The map presented here will provide a genetic framework for mapping the qualitative and quantitative trait in peanut.

  5. A SSR-based composite genetic linkage map for the cultivated peanut (Arachis hypogaea L. genome

    Directory of Open Access Journals (Sweden)

    Li Shaoxiong

    2010-01-01

    Full Text Available Abstract Background The construction of genetic linkage maps for cultivated peanut (Arachis hypogaea L. has and continues to be an important research goal to facilitate quantitative trait locus (QTL analysis and gene tagging for use in a marker-assisted selection in breeding. Even though a few maps have been developed, they were constructed using diploid or interspecific tetraploid populations. The most recently published intra-specific map was constructed from the cross of cultivated peanuts, in which only 135 simple sequence repeat (SSR markers were sparsely populated in 22 linkage groups. The more detailed linkage map with sufficient markers is necessary to be feasible for QTL identification and marker-assisted selection. The objective of this study was to construct a genetic linkage map of cultivated peanut using simple sequence repeat (SSR markers derived primarily from peanut genomic sequences, expressed sequence tags (ESTs, and by "data mining" sequences released in GenBank. Results Three recombinant inbred lines (RILs populations were constructed from three crosses with one common female parental line Yueyou 13, a high yielding Spanish market type. The four parents were screened with 1044 primer pairs designed to amplify SSRs and 901 primer pairs produced clear PCR products. Of the 901 primer pairs, 146, 124 and 64 primer pairs (markers were polymorphic in these populations, respectively, and used in genotyping these RIL populations. Individual linkage maps were constructed from each of the three populations and a composite map based on 93 common loci were created using JoinMap. The composite linkage maps consist of 22 composite linkage groups (LG with 175 SSR markers (including 47 SSRs on the published AA genome maps, representing the 20 chromosomes of A. hypogaea. The total composite map length is 885.4 cM, with an average marker density of 5.8 cM. Segregation distortion in the 3 populations was 23.0%, 13.5% and 7.8% of the markers

  6. 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.

  7. Linkage analysis of five Chinese families with arrhythmogenic right ventricular cardiomyopathy using microsatellite genetic markers

    Institute of Scientific and Technical Information of China (English)

    黄峻; 杨春梅; 马立隽; 单其俊; 许迪; 华子春; 曹克将

    2003-01-01

    Objective To explore the linkage relationship between specific genetic markers and arrhythmogenic right ventricular cardiomyopathy (ARVC) in Chinese pedigrees.Methods The microsatellite genetic markers D2S152, D14S252, and D10S1664 were studied for their linkages to ARVC in five Chinese ARVC pedigrees and a normal population of 121 Chinese individuals. Genomic DNA of the pedigrees and normal population was amplified using PCR techniques. Denaturing polyacrylamide sequencing gel (4%) electrophoresis was used to detect microsatellite repeat polymorphisms. Gels were silver-stained. A classical linkage analysis program was used assuming models of autosomal dominance and recession. Results The logarithm of the odds (LOD) scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were 2.174, -0.589, -∞, - (indicating that linkage is not supported in this mode), and -∞ respectively in autosomal dominant model (recombination fraction=0.000 respectively)and were -∞, -∞, -∞, -∞, and 0.182 respectively in the autosomal recessive model. The LOD scores of D14S252 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -, -∞, -, and 0 respectively in autosomal dominant model, and were -∞, -0.812, -∞, -∞, and 0.087 respectively in autosomal recessive model. The LOD scores of D2S152 with ARVC in LW, WD, DS, LC and TY pedigrees were -, -0.539, -, and 0.602 respectively in autosomal dominant model and were -, -∞, -∞, -∞, and -∞ respectively in autosomal recessive model. Conclusions The LOD score for D2S152 in the LW pedigree was 2.174, indicating that the chance of linkage is about 150∶ 1. This suggests that there is a possible ARVC-related gene near this marker. There were no clear linkage relationships between ARVC and D10S1664 and D14S252 in this family, and no linkages between ARVC and any of the three genetic markers in the other four families. These results also suggest that there is genetic heterogeneity in LW and in the other pedigrees.

  8. SSR-based genetic linkage map of Cucurbita moschata and its synteny with Cucurbita pepo.

    Science.gov (United States)

    Gong, L; Pachner, M; Kalai, K; Lelley, T

    2008-11-01

    The first SSR-based genetic linkage map of Cucurbita moschata was created by integrating the maps of two F2 populations with one common parent developed from the crosses Waltham Butternut (WB) x Nigerian Local (NL) and ZHOU (a hull-less type) x WB. The integrated C. moschata map comprises 205 SSR markers and two morphological traits (Gr and n). The map is composed of 27 linkage groups with a marker density of 7 cM. Comparing the C. moschata map with the published Cucurbita pepo map, we found a high level of macrosynteny. Seventy-two of 76 common SSR markers between C. moschata and C. pepo were located in homologous linkage groups. These markers in general have conserved orders and similar genetic distances; they represent orthologous loci. A reference map based on these SSRs was obtained. No major chromosomal rearrangement between the two species could be detected at present, although four SSR markers were mapped in nonhomologous linkage groups. The comparative alignment of SSR markers did not provide any indication of a possible ancient polyploid origin of the species. The comparative mapping of C. moschata and C. pepo reported here will be useful for further studies on Cucurbit evolution, gene isolation, and breeding work.

  9. Identifying trait clusters by linkage profiles: application in genetical genomics.

    Science.gov (United States)

    Sampson, Joshua N; Self, Steven G

    2008-04-01

    Genes often regulate multiple traits. Identifying clusters of traits influenced by a common group of genes helps elucidate regulatory networks and can improve linkage mapping. We show that the Pearson correlation coefficient, rho L, between two LOD score profiles can, with high specificity and sensitivity, identify pairs of genes that have their transcription regulated by shared quantitative trait loci (QTL). Furthermore, using theoretical and/or empirical methods, we can approximate the distribution of rho L under the null hypothesis of no common QTL. Therefore, it is possible to calculate P-values and false discovery rates for testing whether two traits share common QTL. We then examine the properties of rho L through simulation and use rho L to cluster genes in a genetical genomics experiment examining Saccharomyces cerevisiae. Simulations show that rho L can have more power than the clustering methods currently used in genetical genomics. Combining experimental results with Gene Ontology (GO) annotations show that genes within a purported cluster often share similar function. R-code included in online Supplementary Material.

  10. Evidence for an asthma risk locus on chromosome Xp: a replication linkage study

    DEFF Research Database (Denmark)

    Brasch-Andersen, C; Møller, M U; Haagerup, A;

    2008-01-01

    BACKGROUND: Asthma is a complex genetic disorder characterized by chronic inflammation in the airways. Identification of genetic risk factors for asthma has been complicated due to genetic heterogeneity and influence from environmental risk factors. Despite the fact that multiple genetic linkage...... studies have been carried out the results are still conflicting and call for replication experiments. A Danish genome-wide scan has prior reported evidence for candidate regions for asthma susceptibility genes on chromosomes 1p, 5q, 6p, 12q and Xp. Linkage to chromosome 12q was later confirmed in the same...... replication sample as used in the present study. The aim of the study was to replicate linkage to candidate regions for asthma in an independent Danish sample. METHODS: We performed a replication study investigating linkage to candidate regions for asthma on chromosomes 1p36.31-p36.21, 5q15-q23.2, 6p24.3-p22...

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

    Science.gov (United States)

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

    2017-07-14

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

  12. Efficient and accurate construction of genetic linkage maps from the minimum spanning tree of a graph.

    Directory of Open Access Journals (Sweden)

    Yonghui Wu

    2008-10-01

    Full Text Available Genetic linkage maps are cornerstones of a wide spectrum of biotechnology applications, including map-assisted breeding, association genetics, and map-assisted gene cloning. During the past several years, the adoption of high-throughput genotyping technologies has been paralleled by a substantial increase in the density and diversity of genetic markers. New genetic mapping algorithms are needed in order to efficiently process these large datasets and accurately construct high-density genetic maps. In this paper, we introduce a novel algorithm to order markers on a genetic linkage map. Our method is based on a simple yet fundamental mathematical property that we prove under rather general assumptions. The validity of this property allows one to determine efficiently the correct order of markers by computing the minimum spanning tree of an associated graph. Our empirical studies obtained on genotyping data for three mapping populations of barley (Hordeum vulgare, as well as extensive simulations on synthetic data, show that our algorithm consistently outperforms the best available methods in the literature, particularly when the input data are noisy or incomplete. The software implementing our algorithm is available in the public domain as a web tool under the name MSTmap.

  13. Genetic Mapping in Xenopus Laevis: Eight Linkage Groups Established

    OpenAIRE

    Graf, J. D.

    1989-01-01

    Inheritance of alleles at 29 electrophoretically detected protein loci and one pigment locus (albinism) was analyzed in Xenopus laevis by backcrossing multiply heterozygous individuals generated by intersubspecies hybridization. Pairwise linkage tests revealed eight classical linkage groups. These groups have been provisionally numbered from 1 to 8 in an arbitrarily chosen order. Linkage group 1 includes ALB-2 (albumin), ADH-1 (alcohol dehydrogenase), NP (nucleoside phosphorylase), and a(p) (...

  14. Viral Genetic Linkage Analysis in the Presence of Missing Data.

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    Shelley H Liu

    Full Text Available Analyses of viral genetic linkage can provide insight into HIV transmission dynamics and the impact of prevention interventions. For example, such analyses have the potential to determine whether recently-infected individuals have acquired viruses circulating within or outside a given community. In addition, they have the potential to identify characteristics of chronically infected individuals that make their viruses likely to cluster with others circulating within a community. Such clustering can be related to the potential of such individuals to contribute to the spread of the virus, either directly through transmission to their partners or indirectly through further spread of HIV from those partners. Assessment of the extent to which individual (incident or prevalent viruses are clustered within a community will be biased if only a subset of subjects are observed, especially if that subset is not representative of the entire HIV infected population. To address this concern, we develop a multiple imputation framework in which missing sequences are imputed based on a model for the diversification of viral genomes. The imputation method decreases the bias in clustering that arises from informative missingness. Data from a household survey conducted in a village in Botswana are used to illustrate these methods. We demonstrate that the multiple imputation approach reduces bias in the overall proportion of clustering due to the presence of missing observations.

  15. Genetic mapping of X-linked ocular albinism: Linkage analysis in a large Newfoundland kindred

    Energy Technology Data Exchange (ETDEWEB)

    Charles, S.J.; Moore, A.T.; Barton, D.E.; Yates, J.R.W. (Addenbrooke' s Hospital, Cambridge (United Kingdom)); Green, J.S. (Memorial Univ. of Newfoundland, St. John' s (Canada))

    1993-04-01

    Genetic linkage studies in a large Newfoundland family affected by X-linked ocular albinism (OA1) showed linkage to markers from Xp22.3. One recombinant mapped the disease proximal to DXS143 (dic56) and two recombinants mapped the disease distal to DXS85 (782). Combining the data with that from 16 British families previously published confirmed close linkage between OA1 and DXS143 (dic56; Z[sub max] = 21.96 at [theta] = 0.01, confidence interval (CI) 0.0005--0.05) and linkage to DXS85 (782; Z[sub max] = 17.60 at [theta] = 0.07, CI = 0.03--0.13) and DXS237 (GMGX9; Z[sub max] = 15.20 at [theta] = 0.08, CI = 0.03--0.15). Multipoint analysis (LINKMAP) gave the most likely order as Xpter-XG-DXS237-DXS143-OA1-DXS85, with odds of 48:1 over the order Xpter-XG-DXS237-OA1-DXS143-DXS85, and odds exceeding 10[sup 10]:1 over other locations for the disease locus. 11 refs., 1 fig., 1 tab.

  16. The optimal design for hypothesis test and its application in genetic linkage analysis

    Institute of Scientific and Technical Information of China (English)

    XIE; Minyu(谢民育); LI; Zhaohai(李照海)

    2003-01-01

    This paper proposes a class of linear models with inequable variance, based on background in genetic linkage analysis, and considers the optimal design problem for the hypothesis test of the parameters in such models. To assess a design for the test, a frame of decision theory is established. Under this frame, an admissible minimax design is obtained. It is shown to be not only admissible and minimax in genetic linkage analysis, but best among a reasonable subclass of designs. The power of the test in genetic linkage analysis is substantially improved by using this optimal design.

  17. Quantitative genetics theory for non-inbred populations in linkage disequilibrium

    Directory of Open Access Journals (Sweden)

    José Marcelo Soriano Viana

    2004-01-01

    Full Text Available Although linkage disequilibrium, epistasis and inbreeding are common phenomena in genetic systems that control quantitative traits, theory development and analysis are very complex, especially when they are considered together. The objective of this study is to offer additional quantitative genetics theory to define and analyze, in relation to non-inbred cross pollinating populations, components of genotypic variance, heritabilities and predicted gains, assuming linkage disequilibrium and absence of epistasis. The genotypic variance and its components, additive and due to dominance genetic variances, are invariant over the generations only in regard to completely linked genes and to those in equilibrium. When the population is structured in half-sib families, the additive variance in the parents' generation and the genotypic variance in the population can be estimated. When the population is structured in full-sib families, none of the components of genotypic variance can be estimated. The narrow sense heritability level at plant level can be estimated from the parent-offspring or mid parent-offspring regression. When there is dominance, the narrow sense heritability estimate in the in F2 is biased due to linkage disequilibrium when estimated by the Warner method, but not when estimated by means of the plant F2-family F3 regression. The bias is proportional to the number of pairs of linked genes, without independent assortment, and to the degree of dominance, and tends to be positive when genes in the coupling phase predominate or negative and of higher value when genes in the repulsion phase predominate. Linkage disequilibrium is also cause of bias in estimates of the narrow sense heritabilities at full-sib family mean and at plant within half-sib and full-sib families levels. Generally, the magnitude of the bias is proportional to the number of pairs of genes in disequilibrium and to the frequency of recombining gametes.

  18. A genetic map of Peromyscus with chromosomal assignment of linkage groups (a Peromyscus genetic map).

    Science.gov (United States)

    Kenney-Hunt, Jane; Lewandowski, Adrienne; Glenn, Travis C; Glenn, Julie L; Tsyusko, Olga V; O'Neill, Rachel J; Brown, Judy; Ramsdell, Clifton M; Nguyen, Quang; Phan, Tony; Shorter, Kimberly R; Dewey, Michael J; Szalai, Gabor; Vrana, Paul B; Felder, Michael R

    2014-04-01

    The rodent genus Peromyscus is the most numerous and species-rich mammalian group in North America. The naturally occurring diversity within this genus allows opportunities to investigate the genetic basis of adaptation, monogamy, behavioral and physiological phenotypes, growth control, genomic imprinting, and disease processes. Increased genomic resources including a high quality genetic map are needed to capitalize on these opportunities. We produced interspecific hybrids between the prairie deer mouse (P. maniculatus bairdii) and the oldfield mouse (P. polionotus) and scored meiotic recombination events in backcross progeny. A genetic map was constructed by genotyping of backcross progeny at 185 gene-based and 155 microsatellite markers representing all autosomes and the X-chromosome. Comparison of the constructed genetic map with the molecular maps of Mus and Rattus and consideration of previous results from interspecific reciprocal whole chromosome painting allowed most linkage groups to be unambiguously assigned to specific Peromyscus chromosomes. Based on genomic comparisons, this Peromyscus genetic map covers ~83% of the Rattus genome and 79% of the Mus genome. This map supports previous results that the Peromyscus genome is more similar to Rattus than Mus. For example, coverage of the 20 Rattus autosomes and the X-chromosome is accomplished with only 28 segments of the Peromyscus map, but coverage of the 19 Mus autosomes and the X-chromosome requires 40 chromosomal segments of the Peromyscus map. Furthermore, a single Peromyscus linkage group corresponds to about 91% of the rat and only 76% of the mouse X-chromosomes.

  19. Genetic linkage maps for Asian and American lotus constructed using novel SSR markers derived from the genome of sequenced cultivar

    Directory of Open Access Journals (Sweden)

    Yang Mei

    2012-11-01

    Full Text Available Abstract Background The genus Nelumbo Adans. comprises two living species, N. nucifera Gaertan. (Asian lotus and N. lutea Pers. (American lotus. A genetic linkage map is an essential resource for plant genetic studies and crop improvement but has not been generated for Nelumbo. We aimed to develop genomic simple sequence repeat (SSR markers from the genome sequence and construct two genetic maps for Nelumbo to assist genome assembly and integration of a genetic map with the genome sequence. Results A total of 86,089 SSR motifs were identified from the genome sequences. Di- and tri-nucleotide repeat motifs were the most abundant, and accounted for 60.73% and 31.66% of all SSRs, respectively. AG/GA repeats constituted 51.17% of dinucleotide repeat motifs, followed by AT/TA (44.29%. Of 500 SSR primers tested, 386 (77.20% produced scorable alleles with an average of 2.59 per primer, and 185 (37.00% showed polymorphism among two parental genotypes, N. nucifera ‘Chinese Antique’ and N. lutea ‘AL1’, and six progenies of their F1 population. The normally segregating markers, which comprised 268 newly developed SSRs, 37 previously published SSRs and 53 sequence-related amplified polymorphism markers, were used for genetic map construction. The map for Asian lotus was 365.67 cM with 47 markers distributed in seven linkage groups. The map for American lotus was 524.51 cM, and contained 177 markers distributed in 11 genetic linkage groups. The number of markers per linkage group ranged from three to 34 with an average genetic distance of 3.97 cM between adjacent markers. Moreover, 171 SSR markers contained in linkage groups were anchored to 97 genomic DNA sequence contigs of ‘Chinese Antique’. The 97 contigs were merged into 60 scaffolds. Conclusion Genetic mapping of SSR markers derived from sequenced contigs in Nelumbo enabled the associated contigs to be anchored in the linkage map and facilitated assembly of the genome sequences of

  20. Genetic linkage between melanism and winglessness in the ladybird beetle Adalia bipunctata

    NARCIS (Netherlands)

    Lommen, S.T.E.; Jong, de P.W.; Koops, K.G.; Brakefield, P.M.

    2012-01-01

    We report a case of genetic linkage between the two major loci underlying different wing traits in the two-spot ladybird beetle, Adalia bipunctata (L.) (Coleoptera: Coccinellidae): melanism and winglessness. The loci are estimated to be 38.8 cM apart on one of the nine autosomes. This linkage is lik

  1. Genetic recombination in Escherichia coli : I. Relation between linkage of unselected markers and map distance

    NARCIS (Netherlands)

    Verhoef, C.; Haan, P.G. de

    1966-01-01

    A relation between linkage frequency of an unselected marker and transfer time based on a physical exchange of genetic material was developed for Escherichia coli crosses. Crosses performed under standardised conditions have shown that the relation was valid. The linkage frequency is determined by t

  2. A genetic linkage map of hexaploid naked oat constructed with SSR markers

    Institute of Scientific and Technical Information of China (English)

    Gaoyuan; Song; Pengjie; Huo; Bin; Wu; Zongwen; Zhang

    2015-01-01

    Naked oat is a unique health food crop in China. Using 202 F2 individuals derived from a hybrid between the variety 578 and the landrace Sanfensan, we constructed a genetic linkage map consisting of 22 linkage groups covering 2070.50 c M and including 208 simple sequence repeat(SSR) markers. The minimum distance between adjacent markers was0.01 c M and the average was 9.95 c M. Each linkage group contained 2–22 markers. The largest linkage group covered 174.40 c M and the shortest one covered 36.80 c M, with an average of 94.11 c M. Thirty-six markers(17.3%) showing distorted segregation were distributed across linkage groups LG5 to LG22. This map complements published oat genetic maps and is applicable for quantitative trait locus analysis, gene cloning and molecular marker-assisted selection.

  3. Setting up Multiplex Panels for Genetic Testing of Familial Hy¬pertrophic Cardiomyopathy Based on Linkage Analysis

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    Hoorieh SAGHAFI

    2016-03-01

    Full Text Available Background: Familial hypertrophic cardiomyopathy (HCM is caused by mutations in genes encoding cardiac sarcomere proteins. Nowadays genetic testing of HCM plays an important role in clinical practice by contributing to the diagnosis, prognosis, and screening of high-risk individuals. The aim of this study was developing a reliable testing strategy for HCM based on linkage analysis and appropriate for Iranian population.Methods: Six panels of four microsatellite markers surrounding MYH7, MYBPC3, TNNT2, TNNI3, TPM1, and MYL2 genes (24 markers in total were selected for multiplex PCR and fragment length analysis. Characteristics of markers and informativeness of the panels were evaluated in 50 unrelated Iranians. The efficacy of the strategy was verified in a family with HCM.Results: All markers were highly polymorphic. The panels were informative in 96-100% of samples. Multipoint linkage analysis excluded the linkage between the disease and all six genes by obtaining maximum LOD score ≤-2.Conclusion: This study suggests a reliable genetic testing method based on linkage analysis between 6 sarcomere genes and familial HCM. It could be applied for diagnostic, predictive, or screening testing in clinical setting. Keywords: Cardiomyopathy, Hypertrophic, Genetic linkage, Diagnosis 

  4. Diversity array technology markers: genetic diversity analyses and linkage map construction in rapeseed (Brassica napus L.).

    Science.gov (United States)

    Raman, Harsh; Raman, Rosy; Nelson, Matthew N; Aslam, M N; Rajasekaran, Ravikesavan; Wratten, Neil; Cowling, Wallace A; Kilian, A; Sharpe, Andrew G; Schondelmaier, Joerg

    2012-01-01

    We developed Diversity Array Technology (DArT) markers for application in genetic studies of Brassica napus and other Brassica species with A or C genomes. Genomic representation from 107 diverse genotypes of B. napus L. var. oleifera (rapeseed, AACC genomes) and B. rapa (AA genome) was used to develop a DArT array comprising 11 520 clones generated using PstI/BanII and PstI/BstN1 complexity reduction methods. In total, 1547 polymorphic DArT markers of high technical quality were identified and used to assess molecular diversity among 89 accessions of B. napus, B. rapa, B. juncea, and B. carinata collected from different parts of the world. Hierarchical cluster and principal component analyses based on genetic distance matrices identified distinct populations clustering mainly according to their origin/pedigrees. DArT markers were also mapped in a new doubled haploid population comprising 131 lines from a cross between spring rapeseed lines 'Lynx-037DH' and 'Monty-028DH'. Linkage groups were assigned on the basis of previously mapped simple sequence repeat (SSRs), intron polymorphism (IP), and gene-based markers. The map consisted of 437 DArT, 135 SSR, 6 IP, and 6 gene-based markers and spanned 2288 cM. Our results demonstrate that DArT markers are suitable for genetic diversity analysis and linkage map construction in rapeseed.

  5. Linkage studies of bipolar disorder with chromosome 18 markers.

    Science.gov (United States)

    Bowen, T; Kirov, G; Gill, M; Spurlock, G; Vallada, H P; Murray, R M; McGuffin, P; Collier, D A; Owen, M J; Craddock, N

    1999-10-15

    Evidence consistent with the existence of genetic linkage between bipolar disorder and three regions on chromosome 18, the pericentromeric region, 18q21, and 18q22-q23 have been reported. Some analyses indicated greater evidence for linkage in pedigrees in which paternal transmission of disease occurs. We have undertaken linkage analyses using 12 highly polymorphic markers spanning these three regions of interest in a sample of 48 U.K. bipolar pedigrees. The sample comprises predominantly nuclear families and includes 118 subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM IV) bipolar I disorder and 147 subjects with broadly defined phenotype. Our data do not provide support for linkage using either parametric or nonparametric analyses. Evidence for linkage was not significantly increased by analyses that allowed for heterogeneity nor by analysing the subset of pedigrees consistent with paternal transmission.

  6. A dense genetic linkage map for common carp and its integration with a BAC-based physical map.

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    Lan Zhao

    Full Text Available BACKGROUND: Common carp (Cyprinus carpio is one of the most important aquaculture species with an annual global production of 3.4 million metric tons. It is also an important ornamental species as well as an important model species for aquaculture research. To improve the economically important traits of this fish, a number of genomic resources and genetic tools have been developed, including several genetic maps and a bacterial artificial chromosome (BAC-based physical map. However, integrated genetic and physical maps are not available to study quantitative trait loci (QTL and assist with fine mapping, positional cloning and whole genome sequencing and assembly. The objective of this study was to integrate the currently available BAC-based physical and genetic maps. RESULTS: The genetic map was updated with 592 novel markers, including 312 BAC-anchored microsatellites and 130 SNP markers, and contained 1,209 genetic markers on 50 linkage groups, spanning 3,565.9 cM in the common carp genome. An integrated genetic and physical map of the common carp genome was then constructed, which was composed of 463 physical map contigs and 88 single BACs. Combined lengths of the contigs and single BACs covered a physical length of 498.75 Mb, or around 30% of the common carp genome. Comparative analysis between common carp and zebrafish genomes was performed based on the integrated map, providing more insights into the common carp specific whole genome duplication and segmental rearrangements in the genome. CONCLUSION: We integrated a BAC-based physical map to a genetic linkage map of common carp by anchoring BAC-associated genetic markers. The density of the genetic linkage map was significantly increased. The integrated map provides a tool for both genetic and genomic studies of common carp, which will help us to understand the genomic architecture of common carp and facilitate fine mapping and positional cloning of economically important traits for

  7. 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

  8. Genome-wide distribution of genetic diversity and linkage disequilibrium in elite sugar beet germplasm

    Directory of Open Access Journals (Sweden)

    Weißleder Knuth

    2011-10-01

    Full Text Available Abstract Background Characterization of population structure and genetic diversity of germplasm is essential for the efficient organization and utilization of breeding material. The objectives of this study were to (i explore the patterns of population structure in the pollen parent heterotic pool using different methods, (ii investigate the genome-wide distribution of genetic diversity, and (iii assess the extent and genome-wide distribution of linkage disequilibrium (LD in elite sugar beet germplasm. Results A total of 264 and 238 inbred lines from the yield type and sugar type inbreds of the pollen parent heterotic gene pools, respectively, which had been genotyped with 328 SNP markers, were used in this study. Two distinct subgroups were detected based on different statistical methods within the elite sugar beet germplasm set, which was in accordance with its breeding history. MCLUST based on principal components, principal coordinates, or lapvectors had high correspondence with the germplasm type information as well as the assignment by STRUCTURE, which indicated that these methods might be alternatives to STRUCTURE for population structure analysis. Gene diversity and modified Roger's distance between the examined germplasm types varied considerably across the genome, which might be due to artificial selection. This observation indicates that population genetic approaches could be used to identify candidate genes for the traits under selection. Due to the fact that r2 >0.8 is required to detect marker-phenotype association explaining less than 1% of the phenotypic variance, our observation of a low proportion of SNP loci pairs showing such levels of LD suggests that the number of markers has to be dramatically increased for powerful genome-wide association mapping. Conclusions We provided a genome-wide distribution map of genetic diversity and linkage disequilibrium for the elite sugar beet germplasm, which is useful for the application of

  9. Construction of a genetic linkage map in Lilium using a RIL mapping population based on SRAP marker

    Directory of Open Access Journals (Sweden)

    Chen Li-Jing

    2015-01-01

    Full Text Available A genetic linkage map of lily was constructed using RILs (recombinant inbred lines population of 180 individuals. This mapping population was developed by crossing Raizan No.1 (Formolongo and Gelria (Longiflomm cultivars through single-seed descent (SSD. SRAPs were generated by using restriction enzymes EcoRI in combination with either MseI. The resulting products were separated by electrophoresis on 6% denaturing polyacrylamide gel and visualized by silver staining. The segregation of each marker and linkage analysis was done using the program Mapmaker3.0. With 50 primer pairs, a total of 189 parental polymorphic bands were detected and 78 were used for mapping. The total map length was 2,135.5 cM consisted of 16 linkage groups. The number of markers in the linkage groups varied from 1 to 12. The length of linkage groups was range from 11.2 cM to 425.9 cM and mean marker interval distance range from 9.4 cM to 345.4 cM individually. The mean marker interval distance between markers was 27.4 cM. The map developed in the present study was the first sequence-related amplified polymorphism markers map of lily constructed with recombinant inbred lines, it could be used for genetic mapping and molecular marker assisted breeding and quantitative trait locus mapping of Lilium.

  10. Construction of a microsatellite-based genetic linkage map for half-smooth tongue sole Cynoglossus semilaevis

    Institute of Scientific and Technical Information of China (English)

    Wentao SONG; Guidong MIAO; Yongwei ZHAO; Yuze NIU; Renyi PANG; Xiaolin LIAO; Changwei SHAO

    2013-01-01

    The half-smooth tongue sole Cynoglossus semilaevis is an important cultured marine fish and a promising model fish for the study of sex determination.Sex-specific genetic linkage maps of half-smooth tongue sole were developed with 567 markers (565 microsatellite markers and two SCAR markers).The parents and F1 progeny (92 individuals) were used as segregating populations.The female map was composed of 480 markers in 21 linkage groups,covering a total of 1388.1 cM,with an average interval 3.06 cM between markers.The male map consisted of 417 markers in 21 linkage groups,spanning 1480.9 cM,with an average interval of 3.75 cM.The female and male maps had 474 and 416 unique positions,respectively.The genome length of half-smooth tongue sole was estimated to be 1522.9 cM for females and 1649.1cM for males.Based on estimations of map length,the female and male maps covered 91.1% and 89.8% of the genome,respectively.Furthermore,two female-specific SCAR markers,f-382 and f-783,were mapped on LG15f (linkage group 15 in female maps).The present study presents a mid-density genetic linkage map for half-smooth tongue sole.These improved genetic linkage maps may facilitate systematic genome searches to identify quantitative trait loci (QTL),such as disease resistance,growth and sex-related traits,and are very useful for marker-assisted selection breeding programs for economically important traits in half-smooth tongue sole [Current Zoology 59 (1):31-52,2013].

  11. The genetic basis of familial hypercholesterolemia: inheritance, linkage, and mutations

    Directory of Open Access Journals (Sweden)

    Isabel De Castro-Orós

    2010-08-01

    Full Text Available Isabel De Castro-Orós1, Miguel Pocoví2, Fernando Civeira11Lipid Unit and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS, Zaragoza, Spain; 2Departamento. Bioquímica y Biología Molecular y Celular. Universidad de Zaragoza, Instituto Aragonés de Ciencias de la Salud (I+CS, Zaragoza, Spain and Ciber de Enfermedades Raras (CIBERER, Instituto de Salud Carlos III, SpainAbstract: Familial hypercholesterolemia (FH is a genetic disorder of lipoprotein metabolism characterized by high plasma concentrations of low-density lipoprotein cholesterol (LDLc, tendon xanthomas, and increased risk of premature coronary heart disease. FH is one of the most common inherited disorders; there are 10,000,000 people with FH worldwide, mainly heterozygotes. The most common FH cause is mutations along the entire gene that encode for LDL receptor (LDLR protein, but it has been also described that mutations in apolipoprotein B (APOB and proprotein convertase subtilisin/kexin type 9 genes produce this phenotype. About 17%–33% of patients with a clinical diagnosis of monogenic hypercholesterolemia do not harbor any genetic cause in the known loci. Because FH has been considered as a public health problem, it is very important for an early diagnosis and treatment. Recent studies have ­demonstrated the influence of the LDLR mutation type in the FH phenotype, associating a more severe clinical phenotype and worse advanced carotid artherosclerosis in patients with null than those with receptor-defective mutations. Since 2004, a molecular FH diagnosis based on a genetic ­diagnostic platform (Lipochip®; Progenika-Biopharma, Derio, Spain has been developed. This analysis completes the adequate clinical diagnosis made by physicians. Our group has recently proposed new FH guidelines with the intention to facilitate the FH diagnosis. The treatment for this disease is based on the benefit of

  12. 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.

  13. Genetic linkage map of Brassica campestris L. Using AFLP and RAPD markers

    Institute of Scientific and Technical Information of China (English)

    卢钢; 曹家树; 陈杭

    2002-01-01

    A genetic linkage map comprised of 131 loci was constructed with an F2 population derived from an inter-subspecific cross between Brassica 'qisihai'. The genetic map included 93 RAPD loci, 36 AFLP loci and 2 morphological loci organized into 10 main linkage groups (LGs) and 2 small groups, covering 1810.9cM with average distance between adjacent markers being approximately 13.8cM. The map is suitable for identification of molecular markers linked to important agronomic traits, QTL analysis, and even for marker-assisted selection in breeding programs of Chinese cabbage and turnip.

  14. A Conservative Meta-Analysis of Linkage and Linkage-Association Studies of Developmental Dyslexia

    Science.gov (United States)

    Grigorenko, Elena L.

    2005-01-01

    Linkage studies of complex phenotypes such as reading ability/disability (developmental dyslexia or reading disorder) and related componential processes, where the effects attributable to individual genes appear to be modest, are critically dependent on the nature and composition of the samples and the phenotypes analyzed. Thus, it might be…

  15. Construction of Genetic Linkage Map and QTL Mapping for Fiber Quality in Upland Cotton

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zheng-sheng

    2008-01-01

    @@ A comprehensive genetic linkage map was constructed using 270 F2:7 recombinant inbred lines from a cross between two upland cotton cultivars Yumian 1 and T586.The linkage map comprised of 604 loci and 57 linkage groups ordered into 25 chromosomes,spanning 3106.9 cM,and approximately accounting for the 69.87~ of the whole cotton genome with an average genetic distance of 5.15 cM between two markers.Based on interval mapping,29 QTLs affecting fiber quality were identified,including 5 QTLs for fiber length,7 QTLs for fiber uniformity,10 QTLs for fiber strength,2 QTLs for fiber elongation,and 5 QTLs for fiber fineness.Seventeen QTLs were mapped on A sub-genome chromosomes,and 12 on D sub-genome.

  16. Construction of the High-Density Genetic Linkage Map and Chromosome Map of Large Yellow Croaker (Larimichthys crocea

    Directory of Open Access Journals (Sweden)

    Jingqun Ao

    2015-11-01

    Full Text Available High-density genetic maps are essential for genome assembly, comparative genomic analysis and fine mapping of complex traits. In this study, 31,191 single nucleotide polymorphisms (SNPs evenly distributed across the large yellow croaker (Larimichthys crocea genome were identified using restriction-site associated DNA sequencing (RAD-seq. Among them, 10,150 high-confidence SNPs were assigned to 24 consensus linkage groups (LGs. The total length of the genetic linkage map was 5451.3 cM with an average distance of 0.54 cM between loci. This represents the densest genetic map currently reported for large yellow croaker. Using 2889 SNPs to target specific scaffolds, we assigned 533 scaffolds, comprising 421.44 Mb (62.04% of the large yellow croaker assembled sequence, to the 24 linkage groups. The mapped assembly scaffolds in large yellow croaker were used for genome synteny analyses against the stickleback (Gasterosteus aculeatus and medaka (Oryzias latipes. Greater synteny was observed between large yellow croaker and stickleback. This supports the hypothesis that large yellow croaker is more closely related to stickleback than to medaka. Moreover, 1274 immunity-related genes and 195 hypoxia-related genes were mapped to the 24 chromosomes of large yellow croaker. The integration of the high-resolution genetic map and the assembled sequence provides a valuable resource for fine mapping and positional cloning of quantitative trait loci associated with economically important traits in large yellow croaker.

  17. Genetic Linkage Analysis of the Natural Colored Fiber and Fuzzless Traits in Cotton

    Institute of Scientific and Technical Information of China (English)

    LI Fu-zhen; QIU Xin-mian; WANG Ju-qin; LU Yan-tin; BAO Li-sheng

    2008-01-01

    @@ Genetic linkage relationship of the natural colored fiber and six fuzzless seed germplasms in obsolete backgrounds of Gossypium hirsutum (AD genome) and G.barbadense were analyzed in the past two years.Three lines of natural brown fiber that were controlled by single dominant genes and two lines of green fiber controlled by another single dominant gene.

  18. Genetic linkage maps of Japanese and European pears aligned to the apple consensus map

    NARCIS (Netherlands)

    Yamamoto, T.; Kimura, T.; Saito, T.; Kotobuki, K.; Matsuta, N.; Liebhard, R.; Gessler, C.; Weg, van de W.E.; Hayashi, T.

    2004-01-01

    Genetic linkage maps of the Japanese pear (Pyrus pyrifolia Nakai) cultivar `Housui¿ and the European pear (Pyrus communis L.) cultivar `Bartlett¿ were constructed based on Amplified Fragment Length Polymorphism markers (AFLPs), Simple Sequence Repeat markers (SSRs) (from pear, apple and Prunus),

  19. Genetic linkage maps of Pinus koraiensis Sieb. et Zucc. based on ...

    African Journals Online (AJOL)

    USER

    2010-08-30

    Aug 30, 2010 ... Genetic linkage maps provide essential information for molecular breeding. ... to plants are: (1) basic knowledge of genomic structure, ... quantitative trait expression. ... 11. A-6. GAA. CTC. 126. 27. 20. A-7. GAA. CTG. 113. 19. 13. A-3 .... combinations) code (the first three letters correspond to the selective ...

  20. Record: a novel method for ordering loci on a genetic linkage map

    NARCIS (Netherlands)

    Os, van H.; Stam, P.; Visser, R.G.F.; Eck, van H.J.

    2005-01-01

    A new method, REcombination Counting and ORDering (RECORD) is presented for the ordering of loci on genetic linkage maps. The method minimizes the total number of recombination events. The search algorithm is a heuristic procedure, combining elements of branch-and-bound with local reshuffling. Since

  1. First genetic linkage map of Taraxacum koksaghyz Rodin based on AFLP, SSR, COS and EST-SSR markers

    Science.gov (United States)

    Arias, Marina; Hernandez, Monica; Remondegui, Naroa; Huvenaars, Koen; van Dijk, Peter; Ritter, Enrique

    2016-01-01

    Taraxacum koksaghyz Rodin (TKS) has been studied in many occasions as a possible alternative source for natural rubber production of good quality and for inulin production. Some tire companies are already testing TKS tire prototypes. There are also many investigations on the production of bio-fuels from inulin and inulin applications for health improvement and in the food industry. A limited amount of genomic resources exist for TKS and particularly no genetic linkage map is available in this species. We have constructed the first TKS genetic linkage map based on AFLP, COS, SSR and EST-SSR markers. The integrated linkage map with eight linkage groups (LG), representing the eight chromosomes of Russian dandelion, has 185 individual AFLP markers from parent 1, 188 individual AFLP markers from parent 2, 75 common AFLP markers and 6 COS, 1 SSR and 63 EST-SSR loci. Blasting the EST-SSR sequences against known sequences from lettuce allowed a partial alignment of our TKS map with a lettuce map. Blast searches against plant gene databases revealed some homologies with useful genes for downstream applications in the future. PMID:27488242

  2. First genetic linkage map of Taraxacum koksaghyz Rodin based on AFLP, SSR, COS and EST-SSR markers.

    Science.gov (United States)

    Arias, Marina; Hernandez, Monica; Remondegui, Naroa; Huvenaars, Koen; van Dijk, Peter; Ritter, Enrique

    2016-08-04

    Taraxacum koksaghyz Rodin (TKS) has been studied in many occasions as a possible alternative source for natural rubber production of good quality and for inulin production. Some tire companies are already testing TKS tire prototypes. There are also many investigations on the production of bio-fuels from inulin and inulin applications for health improvement and in the food industry. A limited amount of genomic resources exist for TKS and particularly no genetic linkage map is available in this species. We have constructed the first TKS genetic linkage map based on AFLP, COS, SSR and EST-SSR markers. The integrated linkage map with eight linkage groups (LG), representing the eight chromosomes of Russian dandelion, has 185 individual AFLP markers from parent 1, 188 individual AFLP markers from parent 2, 75 common AFLP markers and 6 COS, 1 SSR and 63 EST-SSR loci. Blasting the EST-SSR sequences against known sequences from lettuce allowed a partial alignment of our TKS map with a lettuce map. Blast searches against plant gene databases revealed some homologies with useful genes for downstream applications in the future.

  3. Genetic linkage map of a wild genome: genomic structure, recombination and sexual dimorphism in bighorn sheep

    Directory of Open Access Journals (Sweden)

    Miller Joshua M

    2010-09-01

    Full Text Available Abstract Background The construction of genetic linkage maps in free-living populations is a promising tool for the study of evolution. However, such maps are rare because it is difficult to develop both wild pedigrees and corresponding sets of molecular markers that are sufficiently large. We took advantage of two long-term field studies of pedigreed individuals and genomic resources originally developed for domestic sheep (Ovis aries to construct a linkage map for bighorn sheep, Ovis canadensis. We then assessed variability in genomic structure and recombination rates between bighorn sheep populations and sheep species. Results Bighorn sheep population-specific maps differed slightly in contiguity but were otherwise very similar in terms of genomic structure and recombination rates. The joint analysis of the two pedigrees resulted in a highly contiguous map composed of 247 microsatellite markers distributed along all 26 autosomes and the X chromosome. The map is estimated to cover about 84% of the bighorn sheep genome and contains 240 unique positions spanning a sex-averaged distance of 3051 cM with an average inter-marker distance of 14.3 cM. Marker synteny, order, sex-averaged interval lengths and sex-averaged total map lengths were all very similar between sheep species. However, in contrast to domestic sheep, but consistent with the usual pattern for a placental mammal, recombination rates in bighorn sheep were significantly greater in females than in males (~12% difference, resulting in an autosomal female map of 3166 cM and an autosomal male map of 2831 cM. Despite differing genome-wide patterns of heterochiasmy between the sheep species, sexual dimorphism in recombination rates was correlated between orthologous intervals. Conclusions We have developed a first-generation bighorn sheep linkage map that will facilitate future studies of the genetic architecture of trait variation in this species. While domestication has been hypothesized

  4. Meta-analysis of genome-wide linkage studies in BMI and obesity

    NARCIS (Netherlands)

    Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Ohman, Muena; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A.

    Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000

  5. Critical reasoning on causal inference in genome-wide linkage and association studies

    NARCIS (Netherlands)

    Li, Yang; Tesson, Bruno M.; Churchill, Gary A.; Jansen, Ritsert C.

    2010-01-01

    Genome-wide linkage and association studies of tens of thousands of clinical and molecular traits are currently underway, offering rich data for inferring causality between traits and genetic variation. However, the inference process is based on discovering subtle patterns in the correlation between

  6. Meta-analysis of genome-wide linkage studies in BMI and obesity

    NARCIS (Netherlands)

    Saunders, Catherine L.; Chiodini, Benedetta D.; Sham, Pak; Lewis, Cathryn M.; Abkevich, Victor; Adeyemo, Adebowale A.; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S.; Blangero, John; Boehnke, Michael; Borecki, Ingrid B.; Chagnon, Yvon C.; Chen, Wei; Comuzzie, Anthony G.; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F.; Froguel, Philippe; Hanson, Robert L.; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H.; Li, Weidong; Luke, Amy; Martin, Lisa J.; Nash, Matthew; Ohman, Muena; Palmer, Lyle J.; Peltonen, Leena; Perola, Markus; Price, R. Arlen; Redline, Susan; Srinivasan, Sathanur R.; Stern, Michael P.; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A.

    2007-01-01

    Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000

  7. Construction of a genetic linkage map and genetic analysis of domestication related traits in mungbean (Vigna radiata.

    Directory of Open Access Journals (Sweden)

    Takehisa Isemura

    Full Text Available The genetic differences between mungbean and its presumed wild ancestor were analyzed for domestication related traits by QTL mapping. A genetic linkage map of mungbean was constructed using 430 SSR and EST-SSR markers from mungbean and its related species, and all these markers were mapped onto 11 linkage groups spanning a total of 727.6 cM. The present mungbean map is the first map where the number of linkage groups coincided with the haploid chromosome number of mungbean. In total 105 QTLs and genes for 38 domestication related traits were identified. Compared with the situation in other Vigna crops, many linkage groups have played an important role in the domestication of mungbean. In particular the QTLs with high contribution were distributed on seven out of 11 linkage groups. In addition, a large number of QTLs with small contribution were found. The accumulation of many mutations with large and/or small contribution has contributed to the differentiation between wild and cultivated mungbean. The useful QTLs for seed size, pod dehiscence and pod maturity that have not been found in other Asian Vigna species were identified in mungbean, and these QTLs may play the important role as new gene resources for other Asian Vigna species. The results provide the foundation that will be useful for improvement of mungbean and related legumes.

  8. Linkage analysis of quantitative refraction and refractive errors in the Beaver Dam Eye Study.

    Science.gov (United States)

    Klein, Alison P; Duggal, Priya; Lee, Kristine E; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E; Klein, Barbara E K

    2011-07-13

    Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10(-4)), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10(-3) and 1.48 × 10(-3), respectively) and to 7p15 of refraction (empiric P = 9.43 × 10(-4)). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10(-3)), a region previously linked to high myopia. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11.

  9. An integrated genetic linkage map for white clover (Trifolium repens L.) with alignment to Medicago

    Science.gov (United States)

    2013-01-01

    Background White clover (Trifolium repens L.) is a temperate forage legume with an allotetraploid genome (2n=4×=32) estimated at 1093 Mb. Several linkage maps of various sizes, marker sources and completeness are available, however, no integrated map and marker set has explored consistency of linkage analysis among unrelated mapping populations. Such integrative analysis requires tools for homoeologue matching among populations. Development of these tools provides for a consistent framework map of the white clover genome, and facilitates in silico alignment with the model forage legume, Medicago truncatula. Results This is the first report of integration of independent linkage maps in white clover, and adds to the literature on methyl filtered GeneThresher®-derived microsatellite (simple sequence repeat; SSR) markers for linkage mapping. Gene-targeted SSR markers were discovered in a GeneThresher® (TrGT) methyl-filtered database of 364,539 sequences, which yielded 15,647 SSR arrays. Primers were designed for 4,038 arrays and of these, 465 TrGT-SSR markers were used for parental consensus genetic linkage analysis in an F1 mapping population (MP2). This was merged with an EST-SSR consensus genetic map of an independent population (MP1), using markers to match homoeologues and develop a multi-population integrated map of the white clover genome. This integrated map (IM) includes 1109 loci based on 804 SSRs over 1274 cM, covering 97% of the genome at a moderate density of one locus per 1.2 cM. Eighteen candidate genes and one morphological marker were also placed on the IM. Despite being derived from disparate populations and marker sources, the component maps and the derived IM had consistent representations of the white clover genome for marker order and genetic length. In silico analysis at an E-value threshold of 1e-20 revealed substantial co-linearity with the Medicago truncatula genome, and indicates a translocation between T. repens groups 2 and 6 relative to

  10. 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

  11. The Genetic Linkage Map of the Medicinal Mushroom Agaricus subrufescens Reveals Highly Conserved Macrosynteny with the Congeneric Species Agaricus bisporus

    Directory of Open Access Journals (Sweden)

    Marie Foulongne-Oriol

    2016-05-01

    Full Text Available Comparative linkage mapping can rapidly facilitate the transfer of genetic information from model species to orphan species. This macrosynteny analysis approach has been extensively used in plant species, but few example are available in fungi, and even fewer in mushroom crop species. Among the latter, the Agaricus genus comprises the most cultivable or potentially cultivable species. Agaricus bisporus, the button mushroom, is the model for edible and cultivable mushrooms. We have developed the first genetic linkage map for the basidiomycete A. subrufescens, an emerging mushroom crop known for its therapeutic properties and potential medicinal applications. The map includes 202 markers distributed over 16 linkage groups (LG, and covers a total length of 1701 cM, with an average marker spacing of 8.2 cM. Using 96 homologous loci, we also demonstrated the high level of macrosynteny with the genome of A. bisporus. The 13 main LG of A. subrufescens were syntenic to the 13 A. bisporus chromosomes. A disrupted synteny was observed for the three remaining A. subrufescens LG. Electronic mapping of a collection of A. subrufescens expressed sequence tags on A. bisporus genome showed that the homologous loci were evenly spread, with the exception of a few local hot or cold spots of homology. Our results were discussed in the light of Agaricus species evolution process. The map provides a framework for future genetic or genomic studies of the medicinal mushroom A. subrufescens.

  12. The Genetic Linkage Map of the Medicinal Mushroom Agaricus subrufescens Reveals Highly Conserved Macrosynteny with the Congeneric Species Agaricus bisporus

    Science.gov (United States)

    Foulongne-Oriol, Marie; Rocha de Brito, Manuela; Cabannes, Delphine; Clément, Aurélien; Spataro, Cathy; Moinard, Magalie; Dias, Eustáquio Souza; Callac, Philippe; Savoie, Jean-Michel

    2016-01-01

    Comparative linkage mapping can rapidly facilitate the transfer of genetic information from model species to orphan species. This macrosynteny analysis approach has been extensively used in plant species, but few example are available in fungi, and even fewer in mushroom crop species. Among the latter, the Agaricus genus comprises the most cultivable or potentially cultivable species. Agaricus bisporus, the button mushroom, is the model for edible and cultivable mushrooms. We have developed the first genetic linkage map for the basidiomycete A. subrufescens, an emerging mushroom crop known for its therapeutic properties and potential medicinal applications. The map includes 202 markers distributed over 16 linkage groups (LG), and covers a total length of 1701 cM, with an average marker spacing of 8.2 cM. Using 96 homologous loci, we also demonstrated the high level of macrosynteny with the genome of A. bisporus. The 13 main LG of A. subrufescens were syntenic to the 13 A. bisporus chromosomes. A disrupted synteny was observed for the three remaining A. subrufescens LG. Electronic mapping of a collection of A. subrufescens expressed sequence tags on A. bisporus genome showed that the homologous loci were evenly spread, with the exception of a few local hot or cold spots of homology. Our results were discussed in the light of Agaricus species evolution process. The map provides a framework for future genetic or genomic studies of the medicinal mushroom A. subrufescens. PMID:26921302

  13. SSR genetic linkage map construction of pea(Pisum sativum L.) based on Chinese native varieties

    Institute of Scientific and Technical Information of China (English)

    Xuelian; Sun; Tao; Yang; Junjie; Hao; Xiaoyan; Zhang; Rebecca; Ford; Junye; Jiang; Fang; Wang; Jianping; Guan; Xuxiao; Zong

    2014-01-01

    Simple sequence repeat(SSR)markers have previously been applied to linkage mapping of the pea(Pisum sativum L.)genome.However,the transferability of existing loci to the molecularly distinct Chinese winter pea gene pool was limited.A novel set of pea SSR markers was accordingly developed.Together with existing SSR sequences,the genome of the G0003973(winter hardy)×G0005527(cold sensitive)cross was mapped using 190 F2individuals.In total,157 SSR markers were placed in 11 linkage groups with an average interval of 9.7 cM and total coverage of 1518 cM.The novel markers and genetic linkage map will be useful for marker-assisted pea breeding.

  14. Construction of a genetic linkage map for cotton based on SRAP

    Institute of Scientific and Technical Information of China (English)

    LIN Zhongxu; ZHANG Xianlong; NIE Yichun; HE Daohua; WU Maoqing

    2003-01-01

    A genetic linkage map of cotton was con structed with a newly developed molecular marker-SRAP (sequence-related amplified polymorphism) using a population consisting of 129 F2 individuals derived from the interspecific cross of "Handan208" x "Pima90". A total of 136 primer pairs were used to detect polymorphisms between the two parents and 76 primer pairs with better polymorphisms were picked out to analyze the F2 population.285 polymorphic bands were generated in total with an average of 3.75 polymorphic bands per pair of primers. The primer pair showing most polymorphic bands was the combination of me3 and em2, which produced 13 polymorphic bands. The 285 loci were used to construct linkage map with MAPMAKER/EXP3.0 and 237 loci were mapped at a LOD≥3.0 on 39 linkage groups. The total length of the map is 3030.7 cM, covering 65.4% of the whole cotton genome, and the average distance between adjacent markers is 12.79 cM. All the markers are distributed evenly among the linkage groups without clustering of loci. This is the first linkage map of cotton comprised of SRAP markers.

  15. On the Consequences of Purging and Linkage on Fitness and Genetic Diversity

    Directory of Open Access Journals (Sweden)

    Diego Bersabé

    2016-01-01

    Full Text Available Using computer simulation we explore the consequences of linkage on the inbreeding load of an equilibrium population, and on the efficiency of purging and the loss of genetic diversity after a reduction in population size. We find that linkage tends to cause increased inbreeding load due to the build up of coupling groups of (partially recessive deleterious alleles. It also induces associative overdominance at neutral sites but rarely causes increased neutral genetic diversity in equilibrium populations. After a reduction in population size, linkage can cause some delay both for the expression of the inbreeding load and the corresponding purging. However, reasonable predictions can be obtained for the evolution of fitness under inbreeding and purging by using empirical estimates of the inbreeding depression rate. Purging selection against homozygotes for deleterious alleles affects the population’s pedigree. Furthermore, it can slow the loss of genetic diversity compared to that expected from the variance of gametic contributions to the breeding group and even from pedigree inbreeding. Under some conditions, this can lead to a smaller loss of genetic diversity, even below that expected from population size in the absence of selection.

  16. Construction of genetic linkage map of the medicinal and ornamental plant Catharanthus roseus

    Indian Academy of Sciences (India)

    Sarika Gupta; Sashi Pandey-Rai; Suchi Srivastava; Subhas Chandra Naithani; Manoj Prasad; Sushil Kumar

    2007-12-01

    An integrated genetic linkage map of the medicinal and ornamental plant Catharanthus roseus, based on different types of molecular and morphological markers was constructed, using a F2 population of 144 plants. The map defines 14 linkage groups (LGs) and consists of 131 marker loci, including 125 molecular DNA markers (76 RAPD, 3 RAPD combinations; 7 ISSR; 2 EST-SSR from Medicago truncatula and 37 other PCR based DNA markers), selected from a total of 472 primers or primer pairs, and six morphological markers (stem pigmentation, leaf lamina pigmentation and shape, leaf petiole and pod size, and petal colour). The total map length is 1131.9 cM (centiMorgans), giving an average map length and distance between two markers equal to 80.9 cM and 8.6 cM, respectively. The morphological markers/genes were found linked with nearest molecular or morphological markers at distances varying from 0.7 to 11.4 cM. Linkage was observed between the morphological markers concerned with lamina shape and petiole size of leaf on LG1 and leaf, stem and petiole pigmentation and pod size on LG8. This is the first genetic linkage map of C. roseus.

  17. Linkage disequilibrium fine mapping of quantitative trait loci: A simulation study

    Directory of Open Access Journals (Sweden)

    Pérez-Enciso Miguel

    2003-09-01

    Full Text Available Abstract Recently, the use of linkage disequilibrium (LD to locate genes which affect quantitative traits (QTL has received an increasing interest, but the plausibility of fine mapping using linkage disequilibrium techniques for QTL has not been well studied. The main objectives of this work were to (1 measure the extent and pattern of LD between a putative QTL and nearby markers in finite populations and (2 investigate the usefulness of LD in fine mapping QTL in simulated populations using a dense map of multiallelic or biallelic marker loci. The test of association between a marker and QTL and the power of the test were calculated based on single-marker regression analysis. The results show the presence of substantial linkage disequilibrium with closely linked marker loci after 100 to 200 generations of random mating. Although the power to test the association with a frequent QTL of large effect was satisfactory, the power was low for the QTL with a small effect and/or low frequency. More powerful, multi-locus methods may be required to map low frequent QTL with small genetic effects, as well as combining both linkage and linkage disequilibrium information. The results also showed that multiallelic markers are more useful than biallelic markers to detect linkage disequilibrium and association at an equal distance.

  18. Genetic linkage map of Brassica campestris L.using AFLP and RAPD markers

    Institute of Scientific and Technical Information of China (English)

    卢钢; 陈杭; 等

    2002-01-01

    A genetic linkage map comprised of 131 loci was constructed with an F2 population derived from an inter-subspecific cross between Brassica campestris L.ssp.chinensis cv.aijiaohang” and ssp.rapifera cv.,”'isihai”.The genetic map included 93 RAPD loci,36 AFLP loci and 2 morphological loci organized into 10 main linkage groups(LGs) and 2 small groups,covering 1810.9cM with average distance between adjacent markers being approximately 13.8cM.The map is suitable for identification of molecular markers linked to important agronomic traits.QTL analysis,and even for marker-assisted selection in breeding programs of Chinese cabbage and turnip.

  19. A genome-wide linkage study of bipolar disorder and co-morbid migraine

    DEFF Research Database (Denmark)

    Oedegaard, K. J.; Greenwood, T. A.; Lunde, Asger

    2010-01-01

    Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genomewide linkage studies in BPAD...... that using migraine comorbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with comorbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar...... osome 4 (not co-segregating with BPAD) in a sample of BPAD families with comorbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a gene for the migraine/BPAD phenotype. Together these data suggest that some genes may predispose to both bipolar disorder and migraine....

  20. Joint multi-population analysis for genetic linkage of bipolar disorder or "wellness" to chromosome 4p.

    Science.gov (United States)

    Visscher, P M; Haley, C S; Ewald, H; Mors, O; Egeland, J; Thiel, B; Ginns, E; Muir, W; Blackwood, D H

    2005-02-05

    To test the hypothesis that the same genetic loci confer susceptibility to, or protection from, disease in different populations, and that a combined analysis would improve the map resolution of a common susceptibility locus, we analyzed data from three studies that had reported linkage to bipolar disorder in a small region on chromosome 4p. Data sets comprised phenotypic information and genetic marker data on Scottish, Danish, and USA extended pedigrees. Across the three data sets, 913 individuals appeared in the pedigrees, 462 were classified, either as unaffected (323) or affected (139) with unipolar or bipolar disorder. A consensus linkage map was created from 14 microsatellite markers in a 33 cM region. Phenotypic and genetic data were analyzed using a variance component (VC) and allele sharing method. All previously reported elevated test statistics in the region were confirmed with one or both analysis methods, indicating the presence of one or more susceptibility genes to bipolar disorder in the three populations in the studied chromosome segment. When the results from both the VC and allele sharing method were considered, there was strong evidence for a susceptibility locus in the data from Scotland, some evidence in the data from Denmark and relatively less evidence in the data from the USA. The test statistics from the Scottish data set dominated the test statistics from the other studies, and no improved map resolution for a putative genetic locus underlying susceptibility in all three studies was obtained. Studies reporting linkage to the same region require careful scrutiny and preferably joint or meta analysis on the same basis in order to ensure that the results are truly comparable. (c) 2004 Wiley-Liss, Inc.

  1. An ultra-dense SNP linkage map for the octoploid, cultivated strawberry and its application in genetic research

    Science.gov (United States)

    We will present an ultra-dense genetic linkage map for the octoploid, cultivated strawberry (Fragaria x ananassa) consisting of over 13K Axiom® based SNP markers and 150 previously mapped reference SSR loci. The high quality of the map is demonstrated by the short sizes of each of the 28 linkage gro...

  2. Tight genetic linkage of prezygotic barrier loci creates a multifunctional speciation island in Petunia.

    Science.gov (United States)

    Hermann, Katrin; Klahre, Ulrich; Moser, Michel; Sheehan, Hester; Mandel, Therese; Kuhlemeier, Cris

    2013-05-20

    Most flowering plants depend on animal vectors for pollination and seed dispersal. Differential pollinator preferences lead to premating isolation and thus reduced gene flow between interbreeding plant populations. Sets of floral traits, adapted to attract specific pollinator guilds, are called pollination syndromes. Shifts in pollination syndromes have occurred surprisingly frequently, considering that they must involve coordinated changes in multiple genes affecting multiple floral traits. Although the identification of individual genes specifying single pollination syndrome traits is in progress in many species, little is known about the genetic architecture of coadapted pollination syndrome traits and how they are embedded within the genome. Here we describe the tight genetic linkage of loci specifying five major pollination syndrome traits in the genus Petunia: visible color, UV absorption, floral scent production, pistil length, and stamen length. Comparison with other Solanaceae indicates that, in P. exserta and P. axillaris, loci specifying these floral traits have specifically become clustered into a multifunctional "speciation island". Such an arrangement promotes linkage disequilibrium and avoids the dissolution of pollination syndromes by recombination. We suggest that tight genetic linkage provides a mechanism for rapid switches between distinct pollination syndromes in response to changes in pollinator availabilities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. The genetics of colored sequence synesthesia: Suggestive evidence of linkage to 16q and genetic heterogeneity for the condition

    Science.gov (United States)

    Tomson, Steffie N.; Avidan, Nili; Lee, Kwanghyuk; Sarma, Anand K.; Tushe, Rejnal; Milewicz, Dianna M.; Bray, Molly; Leal, Suzanne M.; Eagleman, David M.

    2014-01-01

    Synesthesia is a perceptual condition in which sensory stimulation triggers anomalous sensory experiences. In colored sequence synesthesia (CSS), color experiences are triggered by sequences such as letters or numbers. We performed a family based linkage analysis to identify genetic loci responsible for the increased neural crosstalk underlying CSS. Our results implicate a 23 MB region at 16q12.2-23.1, providing the first step in understanding the molecular basis of CSS. PMID:21504763

  4. Hierarchical Problem Solving with the Linkage Tree Genetic Algorithm

    NARCIS (Netherlands)

    Thierens, D.; Bosman, P.A.N.; Blum, C.; Alba, E.

    2013-01-01

    Hierarchical problems represent an important class of nearly decomposable problems. The concept of near decomposability is central to the study of complex systems. When little a priori information is available, a black box problem solver is needed to optimize these hierarchical problems. The solver

  5. Genetic linkage map and expression analysis of genes expressed in the lamellae of the edible basidiomycete Pleurotus ostreatus.

    Science.gov (United States)

    Park, Sang-Kyu; Peñas, María M; Ramírez, Lucía; Pisabarro, Antonio G

    2006-05-01

    Pleurotus ostreatus is an industrially cultivated basidiomycete with nutritional and environmental applications. Its genome contains 35 Mbp organized in 11 chromosomes. There is currently available a genetic linkage map based predominantly on anonymous molecular markers complemented with the mapping of QTLs controlling growth rate and industrial productivity. To increase the saturation of the existing linkage maps, we have identified and mapped 82 genes expressed in the lamellae. Their manual annotation revealed that 34.1% of the lamellae-expressed and 71.5% of the lamellae-specific genes correspond to previously unknown sequences or to hypothetical proteins without a clearly established function. Furthermore, the expression pattern of some genes provides an experimental basis for studying gene regulation during the change from vegetative to reproductive growth. Finally, the identification of various differentially regulated genes involved in protein metabolism suggests the relevance of these processes in fruit body formation and maturation.

  6. 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.

  7. Second generation genetic linkage map for the gilthead sea bream Sparus aurata L.

    Science.gov (United States)

    Tsigenopoulos, Costas S; Louro, Bruno; Chatziplis, Dimitrios; Lagnel, Jacques; Vogiatzi, Emmanouella; Loukovitis, Dimitrios; Franch, Rafaella; Sarropoulou, Elena; Power, Deborah M; Patarnello, Tomaso; Mylonas, Constantinos C; Magoulas, Antonios; Bargelloni, Luca; Canario, Adelino; Kotoulas, Georgios

    2014-12-01

    An updated second linkage map was constructed for the gilthead sea bream, Sparus aurata L., a fish species of great economic importance for the Mediterranean aquaculture industry. In contrast to the first linkage map which mainly consisted of genomic microsatellites (SSRs), the new linkage map is highly enriched with SSRs found in Expressed Sequence Tags (EST-SSRs), which greatly facilitates comparative mapping with other teleosts. The new map consists of 321 genetic markers in 27 linkage groups (LGs): 232 genomic microsatellites, 85 EST-SSRs and 4 SNPs; of those, 13 markers were linked to LGs but were not ordered. Eleven markers (5 SSRs, 5 EST-SSRs and 1 SNP) are not assigned to any LG. The total length of the sex-averaged map is 1769.7cM, 42% longer than the previously published one, and the number of markers in each LG ranges from 2 to 30. The inter-marker distance varies from 0 to 75.6cM, with an average of 5.75cM. The male and female maps have a length of 1349.2 and 2172.1cM, respectively, and the average distance between markers is 4.38 and 7.05cM, respectively. Comparative mapping with the three-spined stickleback (Gasterosteus acuulatus) chromosomes and scaffolds showed conserved synteny with 132 S. aurata markers (42.9% of those mapped) having a hit on the stickleback genome.

  8. Genetic structure and linkage disequilibrium in landrace populations of barley in Sardinia.

    Science.gov (United States)

    Rodriguez, Monica; Rau, Domenico; O'Sullivan, Donal; Brown, Anthony H D; Papa, Roberto; Attene, Giovanna

    2012-06-01

    Multilocus digenic linkage disequilibria (LD) and their population structure were investigated in eleven landrace populations of barley (Hordeum vulgare ssp. vulgare L.) in Sardinia, using 134 dominant simple-sequence amplified polymorphism markers. The analysis of molecular variance for these markers indicated that the populations were partially differentiated (F(ST) = 0.18), and clustered into three geographic areas. Consistent with this population pattern, STRUCTURE analysis allocated individuals from a bulk of all populations into four genetic groups, and these groups also showed geographic patterns. In agreement with other molecular studies in barley, the general level of LD was low (13% of locus pairs, with P landrace populations, but that epistatic homogenising or diversifying selection was also present. Notably, the variance of the disequilibrium component was relatively high, which implies caution in the pooling of barley lines for association studies. Finally, we compared the analyses of multilocus structure in barley landrace populations with parallel analyses in both composite crosses of barley on the one hand and in natural populations of wild barley on the other. Neither of these serves as suitable mimics of landraces in barley, which require their own study. Overall, the results suggest that these populations can be exploited for LD mapping if population structure is controlled.

  9. A genome-wide linkage study of bipolar disorder and co-morbid migraine

    DEFF Research Database (Denmark)

    Oedegaard, K. J.; Greenwood, T. A.; Lunde, Asger

    2010-01-01

    on chromosome 4q24 for migraine (but not BPAD) with a peak LOD of 2.26. This region has previously been implicated in two independent migraine linkage studies. In additionwe identified a locus on chromosome 20p11 with overlapping elevated LOD scores for both migraine (LOD=1.95) and BPAD (LOD=1.67) phenotypes...... Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal...... osome 4 (not co-segregating with BPAD) in a sample of BPAD families with comorbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a gene for the migraine/BPAD phenotype. Together these data suggest that some genes may predispose to both bipolar disorder and migraine....

  10. SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci

    Institute of Scientific and Technical Information of China (English)

    Yong Yong SHI; Lin HE

    2005-01-01

    In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses of linkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large number of samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study with high efficiency. The platform has been well evaluated by several sets of real data.

  11. Development of di-nucleotide microsatellite markers and construction of genetic linkage map in mango (Mangifera indica L.

    Directory of Open Access Journals (Sweden)

    Chataporn Chunwongse

    2015-04-01

    Full Text Available Forty-two di-nucleotide microsatellite, or simple-sequence repeat (SSR, markers were developed using CA and CTenriched genomic libraries of Mangifera indica L. Six cultivated mangoes and two wild species were tested for primer amplifications. Most loci could amplify M. caloneura Kruz and M. foetida. The average number of alleles per locus was 4.4. The average expected heterozygosity and the maximum polymorphism information content value were 0.57 and 0.53, respectively. The SSRs developed in this study together with 65 SSRs and 145 restriction fragment length polymorphism (RFLP markers reported previously were used in the genetic linkage analysis. A partial genetic linkage map was constructed based on 31 F1 progenies from a cross between ‘Alphonso’ and ‘Palmer’. The map spanned a distance of 529.9 centiMorgan (cM and consisted of 9 microsatellite markers (6 from this study and 67 RFLP markers. The new SSR markers and the present map will be useful for mango genetic studies and breeding applications in the future.

  12. Population Structure, Genetic Variation, and Linkage Disequilibrium in Perennial Ryegrass Populations Divergently Selected for Freezing Tolerance.

    Science.gov (United States)

    Kovi, Mallikarjuna Rao; Fjellheim, Siri; Sandve, Simen R; Larsen, Arild; Rudi, Heidi; Asp, Torben; Kent, Matthew Peter; Rognli, Odd Arne

    2015-01-01

    Low temperature is one of the abiotic stresses seriously affecting the growth of perennial ryegrass (Lolium perenne L.), and freezing tolerance is a complex trait of major agronomical importance in northern and central Europe. Understanding the genetic control of freezing tolerance would aid in the development of cultivars of perennial ryegrass with improved adaptation to frost. The plant material investigated in this study was an experimental synthetic population derived from pair-crosses among five European perennial ryegrass genotypes, representing adaptations to a range of climatic conditions across Europe. A total number of 80 individuals (24 of High frost [HF]; 29 of Low frost [LF], and 27 of Unselected [US]) from the second generation of the two divergently selected populations and an unselected (US) control population were genotyped using 278 genome-wide SNPs derived from perennial ryegrass transcriptome sequences. Our studies investigated the genetic diversity among the three experimental populations by analysis of molecular variance and population structure, and determined that the HF and LF populations are very divergent after selection for freezing tolerance, whereas the HF and US populations are more similar. Linkage disequilibrium (LD) decay varied across the seven chromosomes and the conspicuous pattern of LD between the HF and LF population confirmed their divergence in freezing tolerance. Furthermore, two F st outlier methods; finite island model (fdist) by LOSITAN and hierarchical structure model using ARLEQUIN, both detected six loci under directional selection. These outlier loci are most probably linked to genes involved in freezing tolerance, cold adaptation, and abiotic stress. These six candidate loci under directional selection for freezing tolerance might be potential marker resources for breeding perennial ryegrass cultivars with improved freezing tolerance.

  13. A genetic linkage map of quinoa ( Chenopodium quinoa) based on AFLP, RAPD, and SSR markers.

    Science.gov (United States)

    Maughan, P J; Bonifacio, A; Jellen, E N; Stevens, M R; Coleman, C E; Ricks, M; Mason, S L; Jarvis, D E; Gardunia, B W; Fairbanks, D J

    2004-10-01

    Quinoa ( Chenopodium quinoa Willd.) is an important seed crop for human consumption in the Andean region of South America. It is the primary staple in areas too arid or saline for the major cereal crops. The objective of this project was to build the first genetic linkage map of quinoa. Selection of the mapping population was based on a preliminary genetic similarity analysis of four potential mapping parents. Breeding lines 'Ku-2' and '0654', a Chilean lowland type and a Peruvian Altiplano type, respectively, showed a low similarity coefficient of 0.31 and were selected to form an F(2) mapping population. The genetic map is based on 80 F(2) individuals from this population and consists of 230 amplified length polymorphism (AFLP), 19 simple-sequence repeat (SSR), and six randomly amplified polymorphic DNA markers. The map spans 1,020 cM and contains 35 linkage groups with an average marker density of 4.0 cM per marker. Clustering of AFLP markers was not observed. Additionally, we report the primer sequences and map locations for 19 SSR markers that will be valuable tools for future quinoa genome analysis. This map provides a key starting point for genetic dissection of agronomically important characteristics of quinoa, including seed saponin content, grain yield, maturity, and resistance to disease, frost, and drought. Current efforts are geared towards the generation of more than 200 mapped SSR markers and the development of several recombinant-inbred mapping populations.

  14. Population structure, genetic variation and linkage disequilibrium in perennial ryegrass populations divergently selected for freezing tolerance

    Directory of Open Access Journals (Sweden)

    Mallikarjuna Rao eKovi

    2015-11-01

    Full Text Available Low temperature is one of the abiotic stresses seriously affecting the growth of perennial ryegrass (Lolium perenne L. Understanding the genetic control of freezing tolerance would aid in the development of cultivars of perennial ryegrass with improved adaptation to frost. A total number of 80 individuals (24 of High frost [HF]; 29 of Low frost [LF] and 27 of Unselected [US] from the second generation of the two divergently selected populations and an unselected control population were genotyped using 278 genome-wide SNPs derived from Lolium perenne L. transcriptome sequence. Our studies showed that the HF and LF populations are very divergent after selection for freezing tolerance, whereas the HF and US populations are more similar. Linkage disequilibrium (LD decay varied across the seven chromosomes and the conspicuous pattern of LD between the HF and LF population confirmed their divergence in freezing tolerance. Furthermore, two Fst outlier methods; finite island model (fdist by LOSITAN and hierarchical structure model using ARLEQUIN detected six loci under directional selection. These outlier loci are most probably linked to genes involved in freezing tolerance, cold adaptation and abiotic stress and might be the potential marker resources for breeding perennial ryegrass cultivars with improved freezing tolerance.

  15. Genetic linkage analysis of familial amyotrophic lateral sclerosis using human chromosome 21 microsatellite DNA markers

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, D.R.; Sapp, P.; O`Regan, J.; McKenna-Yasek, D.; Schlumpf, K.S.; Haines, J.L.; Gusella, J.F.; Horvitz, H.R.; Brown, R.H. Jr. [Massachusetts Institute of Technology, Cambridge, MA (United States)

    1994-05-15

    Amyotrophic lateral sclerosis (ALS; Lou Gehrig`s Disease) is a lethal neurodegenerative disease of upper and lower motorneurons in the brain and spinal cord. We previously reported linkage of a gene for familial ALS (FALS) to human chromosome 21 using 4 restriction fragment length polymorphism DNA markers and identified disease-associated mutations in the superoxide dismutase (SOD)-1 gene in some ALS families. We report here the genetic linkage data that led us to examine the SOD-1 gene for mutations. We also report a new microsatellite DNA marker for D21S63, derived from the cosmid PW517. Ten microsatellite DNA markers, including the new marker D21S63, were used to reinvestigate linkage of FALS to chromosome 21. Genetic linkage analysis performed with 13 ALS familes for these 10 DNA markers confirmed the presence of a FALS gene on chromosome 21. The highest total 2-point LOD score for all families was 4.33, obtained at a distance of 10 cM from the marker D21S223. For 5 ALS families linked to chromosome 21, a peak 2-point LOD score of 5.94 was obtained at the DNA marker D21S223. A multipoint score of 6.50 was obtained with the markers D21S213, D21S223, D21S167, and FALS for 5 chromosome 21-linked ALS families. The haplotypes of these families for the 10 DNA markers reveal recombination events that further refined the location of the FALS gene to a segment of approximately 5 megabases (Mb) between D21S213 and D21S219. The only characterized gene within this segment was SOD-1, the structural gene for Cu, Zn SOD. 30 refs., 4 figs., 4 tabs.

  16. Genetic Linkage Mapping of Economically Important Traits in Cultivated Tetraploid Potato (Solanum tuberosum L.).

    Science.gov (United States)

    Massa, Alicia N; Manrique-Carpintero, Norma C; Coombs, Joseph J; Zarka, Daniel G; Boone, Anne E; Kirk, William W; Hackett, Christine A; Bryan, Glenn J; Douches, David S

    2015-09-14

    The objective of this study was to construct a single nucleotide polymorphism (SNP)-based genetic map at the cultivated tetraploid level to locate quantitative trait loci (QTL) contributing to economically important traits in potato (Solanum tuberosum L.). The 156 F1 progeny and parents of a cross (MSL603) between "Jacqueline Lee" and "MSG227-2" were genotyped using the Infinium 8303 Potato Array. Furthermore, the progeny and parents were evaluated for foliar late blight reaction to isolates of the US-8 genotype of Phytophthora infestans (Mont.) de Bary and vine maturity. Linkage analyses and QTL mapping were performed using a novel approach that incorporates allele dosage information. The resulting genetic maps contained 1972 SNP markers with an average density of 1.36 marker per cM. QTL mapping identified the major source of late blight resistance in "Jacqueline Lee." The best SNP marker mapped ~0.54 Mb from a resistance hotspot on the long arm of chromosome 9. For vine maturity, the major-effect QTL was located on chromosome 5 with allelic effects from both parents. A candidate SNP marker for this trait mapped ~0.25 Mb from the StCDF1 gene, which is a candidate gene for the maturity trait. The identification of markers for P. infestans resistance will enable the introgression of multiple sources of resistance through marker-assisted selection. Moreover, the discovery of a QTL for late blight resistance not linked to the QTL for vine maturity provides the opportunity to use marker-assisted selection for resistance independent of the selection for vine maturity classifications.

  17. 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.

  18. Construction of an integrated genetic linkage map for the A genome of Brassica napus using SSR markers derived from sequenced BACs in B. rapa

    Directory of Open Access Journals (Sweden)

    King Graham J

    2010-10-01

    Full Text Available Abstract Background The Multinational Brassica rapa Genome Sequencing Project (BrGSP has developed valuable genomic resources, including BAC libraries, BAC-end sequences, genetic and physical maps, and seed BAC sequences for Brassica rapa. An integrated linkage map between the amphidiploid B. napus and diploid B. rapa will facilitate the rapid transfer of these valuable resources from B. rapa to B. napus (Oilseed rape, Canola. Results In this study, we identified over 23,000 simple sequence repeats (SSRs from 536 sequenced BACs. 890 SSR markers (designated as BrGMS were developed and used for the construction of an integrated linkage map for the A genome in B. rapa and B. napus. Two hundred and nineteen BrGMS markers were integrated to an existing B. napus linkage map (BnaNZDH. Among these mapped BrGMS markers, 168 were only distributed on the A genome linkage groups (LGs, 18 distrubuted both on the A and C genome LGs, and 33 only distributed on the C genome LGs. Most of the A genome LGs in B. napus were collinear with the homoeologous LGs in B. rapa, although minor inversions or rearrangements occurred on A2 and A9. The mapping of these BAC-specific SSR markers enabled assignment of 161 sequenced B. rapa BACs, as well as the associated BAC contigs to the A genome LGs of B. napus. Conclusion The genetic mapping of SSR markers derived from sequenced BACs in B. rapa enabled direct links to be established between the B. napus linkage map and a B. rapa physical map, and thus the assignment of B. rapa BACs and the associated BAC contigs to the B. napus linkage map. This integrated genetic linkage map will facilitate exploitation of the B. rapa annotated genomic resources for gene tagging and map-based cloning in B. napus, and for comparative analysis of the A genome within Brassica species.

  19. Preimplantation genetic diagnosis of X-linked Charcot-Marie-Tooth disease by indirect linkage analysis.

    Science.gov (United States)

    Borgulová, Irena; Putzová, Martina; Soldatova, Inna; Stejskal, David

    2017-08-07

    To present methodical approach of preimplantation genetic diagnosis (PGD) as an option for an unaffected pregnancy in reproductive-age couples who have a genetic risk of the X-linked dominant peripheral neuropathy Charcot-Marie-Tooth type 1 disease. We performed PGD of X-linked Charcot-Marie-Tooth type 1 disease using haplotyping/indirect linkage analysis, when during analysis we reach to exclude embryos that carry a high-risk haplotype linked to the causal mutation p.Leu9Phe in the GJB1 gene. Within the PGD cycle, we examined 4 blastomeres biopsied from cleavage-stage embryos and recommended 3 embryos for transfer. Two embryos were implanted into the uterus; however, it resulted in a singleton pregnancy with a male descendant. Three years later, the couple returned again with spontaneous gravidity. A chorionic biopsy examination of this gravidity ascertained the female sex and a pericentric inversion of chromosome 5 in 70% of the cultivated foetal cells. Using indirect linkage analysis, PGD may help to identify genetic X-linked defects within embryos during screening, thereby circumventing the potential problems with abortion. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  20. Genome-wide linkage scan for the metabolic syndrome: the GENNID study.

    Science.gov (United States)

    Edwards, Karen L; Hutter, Carolyn M; Wan, Jia Yin; Kim, Helen; Monks, Stephanie A

    2008-07-01

    In the United States, the metabolic syndrome (MetS) constitutes a major public health problem with over 47 million persons meeting clinical criteria for MetS. Numerous studies have suggested genetic susceptibility to MetS. The goals of this study were (i) to identify susceptibility loci for MetS in well-characterized families with type 2 diabetes (T2D) in four ethnic groups and (ii) to determine whether evidence for linkage varies across the four groups. The GENNID study (Genetics of NIDDM) is a multicenter study established by the American Diabetes Association in 1993 and comprises a comprehensive, well-characterized resource of T2D families from four ethnic groups (whites, Mexican Americans, African Americans, and Japanese Americans). Principal component factor analysis (PCFA) was used to define quantitative phenotypes of the MetS. Variance components linkage analysis was conducted using microsatellite markers from a 10-cM genome-wide linkage scan, separately in each of the four ethnic groups. Three quantitative MetS factors were identified by PCFA and used as phenotypes for MetS: (i) a weight/waist factor, (ii) a blood pressure factor, and (iii) a lipid factor. Evidence for linkage to each of these factors was observed. For each ethnic group, our results suggest that several regions harbor susceptibility genes for the MetS. The strongest evidence for linkage for MetS phenotypes was observed on chromosome 2 (2q12.1-2q13) in the white sample and on chromosome 3 (3q26.1-3q29) in the Mexican-American sample. In conclusion, the results suggest that several regions harbor MetS susceptibility genes and that heterogeneity may exist across groups.

  1. Advancing the STMS genomic resources for defining new locations on the intraspecific genetic linkage map of chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Gaur, Rashmi; Sethy, Niroj K; Choudhary, Shalu; Shokeen, Bhumika; Gupta, Varsha; Bhatia, Sabhyata

    2011-02-17

    Chickpea (Cicer arietinum L.) is an economically important cool season grain legume crop that is valued for its nutritive seeds having high protein content. However, several biotic and abiotic stresses and the low genetic variability in the chickpea genome have continuously hindered the chickpea molecular breeding programs. STMS (Sequence Tagged Microsatellite Sites) markers which are preferred for the construction of saturated linkage maps in several crop species, have also emerged as the most efficient and reliable source for detecting allelic diversity in chickpea. However, the number of STMS markers reported in chickpea is still limited and moreover exhibit low rates of both inter and intraspecific polymorphism, thereby limiting the positions of the SSR markers especially on the intraspecific linkage maps of chickpea. Hence, this study was undertaken with the aim of developing additional STMS markers and utilizing them for advancing the genetic linkage map of chickpea which would have applications in QTL identification, MAS and for de novo assembly of high throughput whole genome sequence data. A microsatellite enriched library of chickpea (enriched for (GT/CA)n and (GA/CT)n repeats) was constructed from which 387 putative microsatellite containing clones were identified. From these, 254 STMS primers were designed of which 181 were developed as functional markers. An intraspecific mapping population of chickpea, [ICCV-2 (single podded) × JG-62 (double podded)] and comprising of 126 RILs, was genotyped for mapping. Of the 522 chickpea STMS markers (including the double-podding trait, screened for parental polymorphism, 226 (43.3%) were polymorphic in the parents and were used to genotype the RILs. At a LOD score of 3.5, eight linkage groups defining the position of 138 markers were obtained that spanned 630.9 cM with an average marker density of 4.57 cM. Further, based on the common loci present between the current map and the previously published chickpea

  2. Genetic overlap of schizophrenia and bipolar disorder in a high-density linkage survey in the Portuguese Island population.

    Science.gov (United States)

    Fanous, Ayman H; Middleton, Frank A; Gentile, Karen; Amdur, Richard L; Maher, Brion S; Zhao, Zhongming; Sun, Jingchun; Medeiros, Helena; Carvalho, Celia; Ferreira, Susana R; Macedo, Antonio; Knowles, James A; Azevedo, Maria H; Pato, Michele T; Pato, Carlos N

    2012-06-01

    Recent family and genome-wide association studies strongly suggest shared genetic risk factors for schizophrenia (SZ) and bipolar disorder (BP). However, linkage studies have not been used to test for statistically significant genome-wide overlap between them. Forty-seven Portuguese families with sibpairs concordant for SZ, BP, or psychosis (PSY, which includes either SZ or psychotic BP) were genotyped for over 57,000 markers using the Affymetrix 50K Xba SNP array. NPL and Kong and Cox LOD scores were calculated in Merlin for all three phenotypes. Empirical significance was determined using 1,000 gene-dropping simulations. Significance of genome-wide genetic overlap between SZ and BP was determined by the number of simulated BP scans having the same number of loci jointly linked with the real SZ scan, and vice versa. For all three phenotypes, a number of regions previously linked in this sample remained so. For BP, chromosome 1p36 achieved significance (11.54-15.71 MB, LOD = 3.51), whereas it was not even suggestively linked at lower marker densities, as did chromosome 11q14.1 (89.32-90.15 MB, NPL = 4.15). Four chromosomes had loci at which both SZ and BP had NPL ≥ 1.98, which was more than would be expected by chance (empirical P = 0.01 using simulated SZ scans; 0.07 using simulated BP scans), although they did not necessarily meet criteria for suggestive linkage individually. These results suggest that high-density marker maps may provide greater power and precision in linkage studies than lower density maps. They also further support the hypothesis that SZ and BP share at least some risk alleles. Copyright © 2012 Wiley Periodicals, Inc.

  3. Path analytic, sib-pair linkage and co-twin control studies of asthma and atopy

    Energy Technology Data Exchange (ETDEWEB)

    Duffy, D.L.; Healey, S.C.; Martin, N.G. [Queensland Institute of Medical Research, Brisband (Austria)

    1994-09-01

    Asthma and atopy are complex traits with multifactorial determinants, and require appropriate choice of phenotypes and analyses, including a linkage analysis of the putative 11q atopy locus. Participants in a large registry-based twin study of asthma were invited to take part in clinical testing. A total of 863 individuals including 419 complete twin pairs (where one or both members reported a history of wheeze) underwent histamine inhalation challenge, allergen skin prick testing, and venesection. Total serum immunoglobulin E (IgE) and bronchial responsiveness (BR) to histamine were highest in those who had wheezed most recently, and whose skin tests demonstrated allergy to house dust mite, cockroach, and rye grass. In ascertainment-corrected path analyses (FISHER), the heritability of IgE and BR were both 60%. Monozygotic (MZ) co-twin control analyses suggested house dust mite sensitization was the single strongest environmentally controlled risk factor for wheeze, while path analyses suggested genetic determination. In dizygotic (DZ) co-twin control analyses, sensitization to grasses was also an important predictor, suggesting pollinosis to be genetically correlated with wheezing, rather than causative. Multivariate path analyses suggested separate (correlated) genetic factors for BR, IgE, and allergy to house dust mite. A sib-pair (Haseman-Elston) linkage analysis of 220 DZ twin pairs did not support linkage to the high-affinity IgE receptor beta-subunit gene on 11q13 of atopy or BR. More recent linkage analyses that include parental genotyping will also be discussed. We conclude that the atopic phenotype consists of a number of traits with specific genetic allergens. Exposure to particular allergens can then cause specific outcomes, such as asthma.

  4. 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

  5. The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity.

    Science.gov (United States)

    Christensen, G B; Knight, S; Camp, N J

    2009-11-01

    We present the "sumLINK" statistic--the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus--as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the "sumLOD" statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage-based statistics as well. Using 500 genome-wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome-wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta-analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak.

  6. A new genetic linkage map of the zygomycete fungus Phycomyces blakesleeanus.

    Directory of Open Access Journals (Sweden)

    Suman Chaudhary

    Full Text Available Phycomyces blakesleeanus is a member of the subphylum Mucoromycotina. A genetic map was constructed from 121 progeny of a cross between two wild type isolates of P. blakesleeanus with 134 markers. The markers were mostly PCR-RFLPs. Markers were located on 46 scaffolds of the genome sequence, covering more than 97% of the genome. Analysis of the alleles in the progeny revealed nine or 12 linkage groups, depending on the log of the odds (LOD score, across 1583.4 cM at LOD 5. The linkage groups were overlaid on previous mapping data from crosses between mutants, aided by new identification of the mutations in primary metabolism mutant strains. The molecular marker map, the phenotype map and the genome sequence are overall congruent, with some exceptions. The new genetic map provides a genome-wide estimate for recombination, with the average of 33.2 kb per cM. This frequency is one piece of evidence for meiosis during zygospore development in Mucoromycotina species. At the same time as meiosis, transmission of non-recombinant chromosomes is also evident in the mating process in Phycomyces. The new map provides scaffold ordering for the genome sequence and a platform upon which to identify the genes in mutants that are affected in traits of interest, such as carotene biosynthesis, phototropism or gravitropism, using positional cloning.

  7. A sugar beet (Beta vulgaris L.) reference FISH karyotype for chromosome and chromosome-arm identification, integration of genetic linkage groups and analysis of major repeat family distribution.

    Science.gov (United States)

    Paesold, Susanne; Borchardt, Dietrich; Schmidt, Thomas; Dechyeva, Daryna

    2012-11-01

    We developed a reference karyotype for B. vulgaris which is applicable to all beet cultivars and provides a consistent numbering of chromosomes and genetic linkage groups. Linkage groups of sugar beet were assigned to physical chromosome arms by FISH (fluorescent in situ hybridization) using a set of 18 genetically anchored BAC (bacterial artificial chromosome) markers. Genetic maps of sugar beet were correlated to chromosome arms, and North-South orientation of linkage groups was established. The FISH karyotype provides a technical platform for genome studies and can be applied for numbering and identification of chromosomes in related wild beet species. The discrimination of all nine chromosomes by BAC probes enabled the study of chromosome-specific distribution of the major repetitive components of sugar beet genome comprising pericentromeric, intercalary and subtelomeric satellites and 18S-5.8S-25S and 5S rRNA gene arrays. We developed a multicolor FISH procedure allowing the identification of all nine sugar beet chromosome pairs in a single hybridization using a pool of satellite DNA probes. Fiber-FISH was applied to analyse five chromosome arms in which the furthermost genetic marker of the linkage group was mapped adjacently to terminal repetitive sequences on pachytene chromosomes. Only on two arms telomere arrays and the markers are physically linked, hence these linkage groups can be considered as terminally closed making the further identification of distal informative markers difficult. The results support genetic mapping by marker localization, the anchoring of contigs and scaffolds for the annotation of the sugar beet genome sequence and the analysis of the chromosomal distribution patterns of major families of repetitive DNA.

  8. Natural Allelic Diversity, Genetic Structure and Linkage Disequilibrium Pattern in Wild Chickpea

    Science.gov (United States)

    Kujur, Alice; Das, Shouvik; Badoni, Saurabh; Kumar, Vinod; Singh, Mohar; Bansal, Kailash C.; Tyagi, Akhilesh K.; Parida, Swarup K.

    2014-01-01

    Characterization of natural allelic diversity and understanding the genetic structure and linkage disequilibrium (LD) pattern in wild germplasm accessions by large-scale genotyping of informative microsatellite and single nucleotide polymorphism (SNP) markers is requisite to facilitate chickpea genetic improvement. Large-scale validation and high-throughput genotyping of genome-wide physically mapped 478 genic and genomic microsatellite markers and 380 transcription factor gene-derived SNP markers using gel-based assay, fluorescent dye-labelled automated fragment analyser and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass array have been performed. Outcome revealed their high genotyping success rate (97.5%) and existence of a high level of natural allelic diversity among 94 wild and cultivated Cicer accessions. High intra- and inter-specific polymorphic potential and wider molecular diversity (11–94%) along with a broader genetic base (13–78%) specifically in the functional genic regions of wild accessions was assayed by mapped markers. It suggested their utility in monitoring introgression and transferring target trait-specific genomic (gene) regions from wild to cultivated gene pool for the genetic enhancement. Distinct species/gene pool-wise differentiation, admixed domestication pattern, and differential genome-wide recombination and LD estimates/decay observed in a six structured population of wild and cultivated accessions using mapped markers further signifies their usefulness in chickpea genetics, genomics and breeding. PMID:25222488

  9. High-density interspecific genetic linkage mapping provides insights into genomic incompatibility between channel catfish and blue catfish.

    Science.gov (United States)

    Liu, S; Li, Y; Qin, Z; Geng, X; Bao, L; Kaltenboeck, L; Kucuktas, H; Dunham, R; Liu, Z

    2016-02-01

    Catfish is the leading aquaculture species in the United States. The interspecific hybrid catfish produced by mating female channel catfish with male blue catfish outperform both of their parent species in a number of traits. However, mass production of the hybrids has been difficult because of reproductive isolation. Investigations of genome structure and organization of the hybrids provide insights into the genetic basis for maintenance of species divergence in the face of gene flow, thereby helping develop strategies for introgression and efficient production of the hybrids for aquaculture. In this study, we constructed a high-density genetic linkage map using the hybrid catfish system with the catfish 250K SNP array. A total of 26,238 SNPs were mapped to 29 linkage groups, with 12,776 unique marker positions. The linkage map spans approximately 3240 cM with an average intermarker distance of 0.25 cM. A fraction of markers (986 of 12,776) exhibited significant deviation from the expected Mendelian ratio of segregation, and they were clustered in major genomic blocks across 15 LGs, most notably LG9 and LG15. The distorted markers exhibited significant bias for maternal alleles among the backcross progenies, suggesting strong selection against the blue catfish alleles. The clustering of distorted markers within genomic blocks should lend insights into speciation as marked by incompatibilities between the two species. Such findings should also have profound implications for understanding the genomic evolution of closely related species as well as the introgression of hybrid production programs in aquaculture.

  10. Genetic studies in alcohol research

    Energy Technology Data Exchange (ETDEWEB)

    Karp, R.W. [National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (United States)

    1994-12-15

    The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports research to elucidate the specific genetic factors, now largely unknown, which underlie susceptibility to alcoholism and its medical complications (including fetal alcohol syndrome). Because of the genetic complexity and heterogeneity of alcoholism, identification of the multiple underlying factors will require the development of new study designs and methods of analysis of data from human families. While techniques of genetic analysis of animal behavioral traits (e.g., targeted gene disruption, quantitative trait locus (QTL) mapping) are more powerful that those applicable to humans (e.g., linkage and allelic association studies), the validation of animal behaviors as models of aspects of human alcoholism has been problematic. Newly developed methods for mapping QTL influencing animal behavioral traits can not only permit analyses of human family data to be directly informed by the results of animal studies, but can also serve as a novel means of validating animal models of aspects of alcoholism. 55 refs.

  11. Genetic basis of agronomically important traits in sugar beet (Beta vulgaris L.) investigated with joint linkage association mapping.

    Science.gov (United States)

    Reif, Jochen C; Liu, Wenxin; Gowda, Manje; Maurer, Hans Peter; Möhring, Jens; Fischer, Sandra; Schechert, Axel; Würschum, Tobias

    2010-11-01

    Epistatic interactions may contribute substantially to the hybrid performance of sugar beet. The main goal of our study was to dissect the genetic basis of eight important physiological and agronomic traits using two different biometrical models for joint linkage association mapping. A total of 197 genotypes of an elite breeding population were evaluated in multi-location trials and fingerprinted with 194 SNP markers. Two different statistical models were used for the genome-wide scan for marker-trait associations: Model A, which corrects for the genetic background with markers as cofactors and Model B, which additionally models a population effect. Based on the extent of linkage disequilibrium in the parental population, we estimated that for a genome-wide scan at least 100 equally spaced markers are necessary. We mapped across the eight traits 39 QTL for Model A and 22 for Model B. Only 11% of the total number of QTL were identified based on Models A and B, which indicates that both models are complementary. Epistasis was detected only for two out of the eight traits, and contributed only to a minor extent to the genotypic variance. This low relevance of epistasis implies that in sugar beet breeding the prediction of performance of three-way hybrids is feasible with high accuracy based on the means of their single crosses.

  12. Linkage analysis and the study of Mendelian disease in the era of whole exome and genome sequencing.

    Science.gov (United States)

    Teare, M Dawn; Santibañez Koref, Mauro F

    2014-09-01

    Whole exome and whole genome sequencing are now routinely used in the study of inherited disease, and some of their major successes have been the identification of genes involved in disease predisposition in pedigrees where disease seems to follow Mendelian inheritance patterns. These successes include scenarios where only a single individual was sequenced and raise the question whether linkage analysis has become superfluous. Linkage analysis requires genome-wide genotyping on family-based data, and traditionally the linkage analysis was performed before the targeting sequencing stage. However, methods are emerging that seek to exploit the capability of linkage analysis to integrate data both across individuals and across pedigrees. This ability has been exploited to select samples used for sequencing studies and to identify among the variants uncovered by sequencing those mapping to regions likely to contain the gene of interest and, more generally, to improve variant detection. So, although the formal isolated linkage analysis stage is less commonly seen, when uncovering the genetic basis of Mendelian disease, methods relying heavily on genetic linkage analysis principles are being integrated directly into the whole mapping process ranging from sample selection to variant calling and filtering. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Microsatellite markers of water buffalo, Bubalus bubalis - development, characterisation and linkage disequilibrium studies

    Directory of Open Access Journals (Sweden)

    Vaidhegi R

    2009-10-01

    Full Text Available Abstract Background Microsatellite markers are highly polymorphic and widely used in genome mapping and population genetic studies in livestock species. River buffalo, Bubalus bubalis is an economically important livestock species, though only a limited number of microsatellite markers have been reported thus far in this species. Results In the present study, using two different approaches 571 microsatellite markers have been characterized for water buffalo. Of the 571 microsatellite markers, 498 were polymorphic with average heterozygosity of 0.51 on a panel of 24 unrelated buffalo. Fisher exact test was used to detect LD between the marker pairs. Among the 137550 pairs of marker combination, 14.58% pairs showed significant LD (P Conclusion The high conservation of cattle microsatellite loci in water buffalo promises the usefulness of the cattle microsatellites markers on buffalo. The polymorphic markers characterised in this study will contribute to genetic linkage and radiation hybrid mapping of water buffalo and population genetic studies.

  14. Improved Student Linkage of Mendelian and Molecular Genetic Concepts through a Yeast-Based Laboratory Module

    Science.gov (United States)

    Wolyniak, Michael J.

    2013-01-01

    A study of modern genetics requires students to successfully unite the principles of Mendelian genetics with the functions of DNA. Traditional means of teaching genetics are often successful in teaching Mendelian and molecular ideas but not in allowing students to see how the two subjects relate. The laboratory module presented here attempts to…

  15. Genetic linkage of distinct adaptive traits in sympatrically speciating crater lake cichlid fish

    Science.gov (United States)

    Fruciano, Carmelo; Franchini, Paolo; Kovacova, Viera; Elmer, Kathryn R.; Henning, Frederico; Meyer, Axel

    2016-01-01

    Our understanding of how biological diversity arises is limited, especially in the case of speciation in the face of gene flow. Here we investigate the genomic basis of adaptive traits, focusing on a sympatrically diverging species pair of crater lake cichlid fishes. We identify the main quantitative trait loci (QTL) for two eco-morphological traits: body shape and pharyngeal jaw morphology. These traits diverge in parallel between benthic and limnetic species in the repeated adaptive radiations of this and other fish lineages. Remarkably, a single chromosomal region contains the highest effect size QTL for both traits. Transcriptomic data show that the QTL regions contain genes putatively under selection. Independent population genomic data corroborate QTL regions as areas of high differentiation between the sympatric sister species. Our results provide empirical support for current theoretical models that emphasize the importance of genetic linkage and pleiotropy in facilitating rapid divergence in sympatry. PMID:27597183

  16. 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.

  17. Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study.

    Science.gov (United States)

    Ehlers, Cindy L; Gizer, Ian R; Vieten, Cassandra; Wilhelmsen, Kirk C

    2010-04-05

    Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis-related phenotypes of "craving" and "withdrawal" using a family study design. Participants were 2,524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM-IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome-wide significance for linkage (LOD > 3.0) was not found for the DSM-IV cannabis dependence diagnosis; however, linkage analyses of cannabis "craving" and the cannabis withdrawal symptom of "nervous, tense, restless, or irritable" revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, and 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes.

  18. U1 and U2 small nuclear RNA genetic linkage: a novel molecular tool for identification of six sole species (Soleidae, Pleuronectiformes).

    Science.gov (United States)

    Manchado, Manuel; Rebordinos, Laureana; Infante, Carlos

    2006-05-31

    We evaluated the usefulness of a genetic linkage between the U1 and U2 small nuclear RNAs for species identification. Six soles belonging to the genera Solea, Dicologlossa, and Microchirus were studied. A simple methodology based on two single PCRs is described. Reproducible band profiles were generated for all samples. This rapid and discriminatory molecular method is highly promising for determining the authenticity of sole fillets in the food industry.

  19. Linkage disequilibrium and the genetic distance in livestock populations: the impact of inbreeding

    Directory of Open Access Journals (Sweden)

    Baret Philippe V

    2004-05-01

    Full Text Available Abstract Genome-wide linkage disequilibrium (LD is subject to intensive investigation in human and livestock populations since it can potentially reveal aspects of a population history, permit to date them and help in fine-gene mapping. The most commonly used measure of LD between multiallelic loci is the coefficient D'. Data based on D' were recently published in humans, livestock and model animals. However, the properties of this coefficient are not well understood. Its sampling distribution and variance has received recent attention, but its expected behaviour with respect to genetic or physical distance remains unknown. Using stochastic simulations of populations having a finite size, we show that D' fits an exponential function having two parameters of simple biological interpretation: the residual value (rs towards which D' tends as the genetic distance increases and the distance R at which this value is reached. Properties of this model are evaluated as a function of the inbreeding coefficient (F. It was found that R and rs increase when F increases. The proposed model offers opportunities to better understand the patterns and the origins of LD in different populations and along different chromosomes.

  20. Saccharomyces cerevisiae FLO1 Gene Demonstrates Genetic Linkage to Increased Fermentation Rate at Low Temperatures

    Science.gov (United States)

    Deed, Rebecca C.; Fedrizzi, Bruno; Gardner, Richard C.

    2017-01-01

    Low fermentation temperatures are of importance to food and beverage industries working with Saccharomyces cerevisiae. Therefore, the identification of genes demonstrating a positive impact on fermentation kinetics is of significant interest. A set of 121 mapped F1 progeny, derived from a cross between haploid strains BY4716 (a derivative of the laboratory yeast S288C) and wine yeast RM11-1a, were fermented in New Zealand Sauvignon Blanc grape juice at 12.5°. Analyses of five key fermentation kinetic parameters among the F1 progeny identified a quantitative trait locus (QTL) on chromosome I with a significant degree of linkage to maximal fermentation rate (Vmax) at low temperature. Independent deletions of two candidate genes within the region, FLO1 and SWH1, were constructed in the parental strains (with S288C representing BY4716). Fermentation of wild-type and deletion strains at 12.5 and 25° confirmed that the genetic linkage to Vmax corresponds to the S288C version of the FLO1 allele, as the absence of this allele reduced Vmax by ∼50% at 12.5°, but not at 25°. Reciprocal hemizygosity analysis (RHA) between S288C and RM11-1a FLO1 alleles did not confirm the prediction that the S288C version of FLO1 was promoting more rapid fermentation in the opposing strain background, suggesting that the positive effect on Vmax derived from S288C FLO1 may only provide an advantage in haploids, or is dependent on strain-specific cis or trans effects. This research adds to the growing body of evidence demonstrating the role of FLO1 in providing stress tolerance to S. cerevisiae during fermentation. PMID:28143947

  1. Saccharomyces cerevisiae FLO1 Gene Demonstrates Genetic Linkage to Increased Fermentation Rate at Low Temperatures

    Directory of Open Access Journals (Sweden)

    Rebecca C. Deed

    2017-03-01

    Full Text Available Low fermentation temperatures are of importance to food and beverage industries working with Saccharomyces cerevisiae. Therefore, the identification of genes demonstrating a positive impact on fermentation kinetics is of significant interest. A set of 121 mapped F1 progeny, derived from a cross between haploid strains BY4716 (a derivative of the laboratory yeast S288C and wine yeast RM11-1a, were fermented in New Zealand Sauvignon Blanc grape juice at 12.5°. Analyses of five key fermentation kinetic parameters among the F1 progeny identified a quantitative trait locus (QTL on chromosome I with a significant degree of linkage to maximal fermentation rate (Vmax at low temperature. Independent deletions of two candidate genes within the region, FLO1 and SWH1, were constructed in the parental strains (with S288C representing BY4716. Fermentation of wild-type and deletion strains at 12.5 and 25° confirmed that the genetic linkage to Vmax corresponds to the S288C version of the FLO1 allele, as the absence of this allele reduced Vmax by ∼50% at 12.5°, but not at 25°. Reciprocal hemizygosity analysis (RHA between S288C and RM11-1a FLO1 alleles did not confirm the prediction that the S288C version of FLO1 was promoting more rapid fermentation in the opposing strain background, suggesting that the positive effect on Vmax derived from S288C FLO1 may only provide an advantage in haploids, or is dependent on strain-specific cis or trans effects. This research adds to the growing body of evidence demonstrating the role of FLO1 in providing stress tolerance to S. cerevisiae during fermentation.

  2. Linkages among the non-genetically modified soybean, conventional soybean, and corn futures markets in the Tokyo Grain Exchange

    OpenAIRE

    2011-01-01

    The market linkages among the non-genetically modified (non-GM) soybean, conventional soybean, and cor futures markets at the Tokyo Grain Exchange are investigated to find out if the two soybean futures markets and the corn futures market share price information in the presence of unknown breaks. The results reveal that there are market linkages between the non-GM and conventional soybean futures prices and between the non-GM soybean and corn futures prices and that these markets do influence...

  3. A genetic linkage map for hazelnut (Corylus avellana L.) based on RAPD and SSR markers.

    Science.gov (United States)

    Mehlenbacher, Shawn A; Brown, Rebecca N; Nouhra, Eduardo R; Gökirmak, Tufan; Bassil, Nahla V; Kubisiak, Thomas L

    2006-02-01

    A linkage map for European hazelnut (Corylus avellana L.) was constructed using random amplified polymorphic DNA (RAPD) and simple sequence repeat (SSR) markers and the 2-way pseudotestcross approach. A full-sib population of 144 seedlings from the cross OSU 252.146 x OSU 414.062 was used. RAPD markers in testcross configuration, segregating 1:1, were used to construct separate maps for each parent. Fifty additional RAPD loci were assigned to linkage groups as accessory markers whose exact location could not be determined. Markers in intercross configuration, segregating 3:1, were used to pair groups in one parent with their homologues in the other. Eleven groups were identified for each parent, corresponding to the haploid chromosome number of hazelnut (n = x = 11). Thirty of the 31 SSR loci were able to be assigned to a linkage group. The maternal map included 249 RAPD and 20 SSR markers and spanned a distance of 661 cM. The paternal map included 271 RAPD and 28 SSR markers and spanned a distance of 812 cM. The maps are quite dense, with an average of 2.6 cM between adjacent markers. The S-locus, which controls pollen-stigma incompatibility, was placed on chromosome 5S where 6 markers linked within a distance of 10 cM were identified. A locus for resistance to eastern filbert blight, caused by Anisogramma anomala, was placed on chromosome 6R for which two additional markers tightly linked to the dominant allele were identified and sequenced. These maps will serve as a starting point for future studies of the hazelnut genome, including map-based cloning of important genes. The inclusion of SSR loci on the map will make it useful in other populations.

  4. A combined linkage and exome sequencing analysis for electrocardiogram parameters in the Erasmus Rucphen Family study

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    Claudia Tamar Silva

    2016-11-01

    Full Text Available Electrocardiogram (ECG measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies (GWAS of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF. Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05, one for QRS interval (1p35, LOD = 2.52 and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29. Fine-mapping using exome sequence data identified a C > G missense variant (c.713C>G, p.Ser238Cys in the FCRL2 gene associated with QT (rs74608430; P = 2.8 ×10-4, minor allele frequency = 0.019. Heritability analysis demonstrated that the SNP explained 2.42% of the trait’s genetic variability in ERF (P = 0.02. Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 × 10-3 and AMPK stimulated fatty acid oxidation in muscle (P = 4.1 ×10-3. Look-ups in bioinformatics resources showed that expression of FCRL2 is associated with ARHGAP24 and SETBP1 expression. This finding was not replicated in the Rotterdam study. Combining the bioinformatics information with the association and linkage analyses, FCRL2 emerges as a strong candidate gene for QT interval.

  5. Genome-wide evaluation of genetic diversity and linkage disequilibrium in winter and spring triticale (x Triticosecale Wittmack

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    Alheit Katharina V

    2012-06-01

    Full Text Available Abstract Background Recent advances in genotyping with high-density markers nowadays enable genome-wide genomic analyses in crops. A detailed characterisation of the population structure and linkage disequilibrium (LD is essential for the application of genomic approaches and consequently for knowledge-based breeding. In this study we used the triticale-specific DArT array to analyze population structure, genetic diversity, and LD in a worldwide set of 161 winter and spring triticale lines. Results The principal coordinate analysis revealed that the first principal coordinate divides the triticale population into two clusters according to their growth habit. The density distributions of the first ten principal coordinates revealed that several show a distribution indicative of population structure. In addition, we observed relatedness within growth habits which was higher among the spring types than among the winter types. The genome-wide analysis of polymorphic information content (PIC showed that the PIC is variable among and along chromosomes and that especially the R genome of spring types possesses a reduced genetic diversity. We also found that several chromosomes showed regions of high genetic distance between the two growth habits, indicative of divergent selection. Regarding linkage disequilibrium, the A and B genomes showed a similar LD of 0.24 for closely linked markers and a decay within approximately 12 cM. LD in the R genome was lower with 0.19 and decayed within a shorter map distance of approximately 5 cM. The extent of LD was generally higher for the spring types compared to the winter types. In addition, we observed strong variability of LD along the chromosomes. Conclusions Our results confirm winter and spring growth habit are the major contributors to population structure in triticale, and a family structure exists in both growth types. The specific patterns of genetic diversity observed within these types, such as the

  6. Population genetic structure, linkage disequilibrium and effective population size of conserved and extensively raised village chicken populations of Southern Africa

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    Khulekhani Sedwell Khanyile

    2015-02-01

    Full Text Available Extensively raised village chickens are considered a valuable source of biodiversity, with genetic variability developed over thousands of years that ought to be characterised and utilized. Surveys that can reveal a population’s genetic structure and provide an insight into its demographic history will give valuable information to manage and conserve important indigenous animal genetic resources. This study reports population diversity and structure, linkage disequilibrium and effective population sizes of Southern African village chickens and conservation flocks from South Africa. DNA samples from 312 chickens from South African village and conservation flocks (n =146, Malawi (n =30 and Zimbabwe (n =136 were genotyped using the Illumina iSelect chicken SNP60K BeadChip. Population genetic structure analysis distinguished the four conservation flocks from the village chicken populations. Of the four flocks, the Ovambo clustered closer to the village chickens particularly those sampled from South Africa. Clustering of the village chickens followed a geographic gradient whereby South African chickens were closer to those from Zimbabwe than to chickens from Malawi. Different conservation flocks seemed to have maintained different components of the ancestral genomes with a higher proportion of village chicken diversity found in the Ovambo population. Overall population LD averaged over chromosomes ranged from 0.03 ± 0.07 to 0.58 ± 0.41 and averaged 0.15 ± 0.16. Higher LD, ranging from 0.29-0.36, was observed between SNP markers that were less than 10kb apart in the conservation flocks. LD in the conservation flocks steadily decreased to 0.15 (PK and 0.24 (VD at SNP marker interval of 500kb. Genomewide LD decay in the village chickens from Malawi, Zimbabwe and South Africa followed a similar trend as the conservation flocks although the mean LD values for the investigated SNP intervals were lower. The results suggest low effective population

  7. Comparative linkage meta-analysis reveals regionally-distinct, disparate genetic architectures: application to bipolar disorder and schizophrenia.

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    Brady Tang

    Full Text Available New high-throughput, population-based methods and next-generation sequencing capabilities hold great promise in the quest for common and rare variant discovery and in the search for "missing heritability." However, the optimal analytic strategies for approaching such data are still actively debated, representing the latest rate-limiting step in genetic progress. Since it is likely a majority of common variants of modest effect have been identified through the application of tagSNP-based microarray platforms (i.e., GWAS, alternative approaches robust to detection of low-frequency (1-5% MAF and rare (<1% variants are of great importance. Of direct relevance, we have available an accumulated wealth of linkage data collected through traditional genetic methods over several decades, the full value of which has not been exhausted. To that end, we compare results from two different linkage meta-analysis methods--GSMA and MSP--applied to the same set of 13 bipolar disorder and 16 schizophrenia GWLS datasets. Interestingly, we find that the two methods implicate distinct, largely non-overlapping, genomic regions. Furthermore, based on the statistical methods themselves and our contextualization of these results within the larger genetic literatures, our findings suggest, for each disorder, distinct genetic architectures may reside within disparate genomic regions. Thus, comparative linkage meta-analysis (CLMA may be used to optimize low-frequency and rare variant discovery in the modern genomic era.

  8. Microsatellite isolation and marker development in carrot - genomic distribution, linkage mapping, genetic diversity analysis and marker transferability across Apiaceae

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    Yildiz Mehtap

    2011-08-01

    Full Text Available Abstract Background The Apiaceae family includes several vegetable and spice crop species among which carrot is the most economically important member, with ~21 million tons produced yearly worldwide. Despite its importance, molecular resources in this species are relatively underdeveloped. The availability of informative, polymorphic, and robust PCR-based markers, such as microsatellites (or SSRs, will facilitate genetics and breeding of carrot and other Apiaceae, including integration of linkage maps, tagging of phenotypic traits and assisting positional gene cloning. Thus, with the purpose of isolating carrot microsatellites, two different strategies were used; a hybridization-based library enrichment for SSRs, and bioinformatic mining of SSRs in BAC-end sequence and EST sequence databases. This work reports on the development of 300 carrot SSR markers and their characterization at various levels. Results Evaluation of microsatellites isolated from both DNA sources in subsets of 7 carrot F2 mapping populations revealed that SSRs from the hybridization-based method were longer, had more repeat units and were more polymorphic than SSRs isolated by sequence search. Overall, 196 SSRs (65.1% were polymorphic in at least one mapping population, and the percentage of polymophic SSRs across F2 populations ranged from 17.8 to 24.7. Polymorphic markers in one family were evaluated in the entire F2, allowing the genetic mapping of 55 SSRs (38 codominant onto the carrot reference map. The SSR loci were distributed throughout all 9 carrot linkage groups (LGs, with 2 to 9 SSRs/LG. In addition, SSR evaluations in carrot-related taxa indicated that a significant fraction of the carrot SSRs transfer successfully across Apiaceae, with heterologous amplification success rate decreasing with the target-species evolutionary distance from carrot. SSR diversity evaluated in a collection of 65 D. carota accessions revealed a high level of polymorphism for these

  9. Identification of a glutamic acid repeat polymorphism of ALMS1 as a novel genetic risk marker for early-onset myocardial infarction by genome-wide linkage analysis.

    Science.gov (United States)

    Ichihara, Sahoko; Yamamoto, Ken; Asano, Hiroyuki; Nakatochi, Masahiro; Sukegawa, Mayo; Ichihara, Gaku; Izawa, Hideo; Hirashiki, Akihiro; Takatsu, Fumimaro; Umeda, Hisashi; Iwase, Mitsunori; Inagaki, Haruo; Hirayama, Haruo; Sone, Takahito; Nishigaki, Kazuhiko; Minatoguchi, Shinya; Cho, Myeong-Chan; Jang, Yangsoo; Kim, Hyo-Soo; Park, Jeong E; Tada-Oikawa, Saeko; Kitajima, Hidetoshi; Matsubara, Tatsuaki; Sunagawa, Kenji; Shimokawa, Hiroaki; Kimura, Akinori; Lee, Jong-Young; Murohara, Toyoaki; Inoue, Ituro; Yokota, Mitsuhiro

    2013-12-01

    Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention. We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene (ALMS1) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI. The glutamic acid repeat polymorphism of ALMS1 identified in the present study may provide insight into the pathogenesis of early-onset MI.

  10. Genetic linkage of bipolar disorder to chromosome 6q22 is a consistent finding in Portuguese subpopulations and may generalize to broader populations.

    Science.gov (United States)

    Pato, Carlos N; Middleton, Frank A; Gentile, Karen L; Morley, Christopher P; Medeiros, Helena; Macedo, Antonio; Azevedo, M Helena; Pato, Michele T

    2005-04-05

    We recently reported genome-wide significant linkage to chromosome 6q for bipolar disorder, in a study of 25 Portuguese families, using the Human Mapping Assay Xba 131 (HMA10K). To explore the generalizability of this finding, we reanalyzed our SNP linkage data according to the families' geographic origin. Specifically, the 25 families included 20 families from the Portuguese island collection (PIC; 15 families from the Azores Islands and 5 from the Madeira Islands) and 5 families from continental Portugal. Non-parametric linkage analysis (NPL) was performed as previously described and indicated that each of these subpopulations showed evidence of linkage for the same region. To further address the potential generalizability of these findings to other populations, we have also examined allelic heterozygosity in our subpopulations and in three reference populations (Caucasian, East Asian, and African-American). This analysis indicated that the PIC population is highly correlated to the Caucasian reference population (R = 0.86) for all of chromosome 6. In contrast allelic heterozygosity was more weakly correlated between PIC and both East Asian (R = 0.37) and African-American (R = 0.32) reference populations. Taken together these observations suggest a shared genetic liability among Portuguese populations for bipolar disorder on chromosome 6q, and that the PIC population is likely representative of Caucasians in general. Copyright 2005 Wiley-Liss, Inc.

  11. Genetic mapping of horizontal stripes in Lake Victoria cichlid fishes: benefits and pitfalls of using RAD markers for dense linkage mapping.

    Science.gov (United States)

    Henning, Frederico; Lee, Hyuk Je; Franchini, Paolo; Meyer, Axel

    2014-11-01

    The genetic dissection of naturally occurring phenotypes sheds light on many fundamental and longstanding questions in speciation and adaptation and is a central research topic in evolutionary biology. Until recently, forward-genetic approaches were virtually impossible to apply to nonmodel organisms, but the development of next-generation sequencing techniques eases this difficulty. Here, we use the ddRAD-seq method to map a colour trait with a known adaptive function in cichlid fishes, well-known textbook examples for rapid rates of speciation and astonishing phenotypic diversification. A suite of phenotypic key innovations is related to speciation and adaptation in cichlids, among which body coloration features prominently. The focal trait of this study, horizontal stripes, evolved in parallel in several cichlid radiations and is associated with piscivorous foraging behaviour. We conducted interspecific crosses between Haplochromis sauvagei and H. nyererei and constructed a linkage map with 867 SNP markers distributed on 22 linkage groups and total size of 1130.63 cM. Lateral stripes are inherited as a Mendelian trait and map to a single genomic interval that harbours a paralog of a gene with known function in stripe patterning. Dorsolateral and mid-lateral stripes were always coinherited and are thus under the same genetic control. Additionally, we directly quantify the genotyping error rates in RAD markers and offer guidelines for identifying and dealing with errors. Uncritical marker selection was found to severely impact linkage map construction. Fortunately, by applying appropriate quality control steps, a genotyping accuracy of >99.9% can be reached, thus allowing for efficient linkage mapping of evolutionarily relevant traits.

  12. A Comparative Study of Linkage Indexes: Co-assignee, Reciprocal Citation, Patent Coupling and Co-patent

    Directory of Open Access Journals (Sweden)

    Szu-chia Scarlett Lo

    2010-06-01

    Full Text Available Four indexes including co-assignees, reciprocal citation, patent coupling and co-patent were examined in this study to reveal the meanings of the correlations generated via different citation linkages. This study includes 6,274 genetic engineering patents, and 16 primary assignees identified by Bradford model analysis as the base for correlation analysis. The results show that there are four cluster types, including technological affiliated, technological competitor correlated, commercial collaborated and technological isolated.

  13. A genome-wide linkage study of bipolar disorder and co-morbid migraine: replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11.

    Science.gov (United States)

    Oedegaard, K J; Greenwood, T A; Lunde, A; Fasmer, O B; Akiskal, H S; Kelsoe, J R

    2010-04-01

    Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genome-wide linkage studies in BPAD and migraine have shown overlapping regions of linkage on chromosomes, and two functionally similar voltage-dependent calcium channels CACNA1A and CACNA1C have been identified in familial hemiplegic migraine and recently implicated in two whole genome BPAD association studies, respectively. We hypothesized that using migraine co-morbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with co-morbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal on chromosome 4q24 for migraine (but not BPAD) with a peak LOD of 2.26. This region has previously been implicated in two independent migraine linkage studies. In addition we identified a locus on chromosome 20p11 with overlapping elevated LOD scores for both migraine (LOD=1.95) and BPAD (LOD=1.67) phenotypes. This region has previously been implicated in two BPAD linkage studies, and, interestingly, it harbors a known potassium dependant sodium/calcium exchanger gene, SLC24A3, that plays a critical role in neuronal calcium homeostasis. Our findings replicate a previously identified migraine linkage locus on chromosome 4 (not co-segregating with BPAD) in a sample of BPAD families with co-morbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a

  14. Genome-wide linkage scan identifies two novel genetic loci for coronary artery disease: in GeneQuest families.

    Science.gov (United States)

    Gao, Hanxiang; Li, Lin; Rao, Shaoqi; Shen, Gongqing; Xi, Quansheng; Chen, Shenghan; Zhang, Zheng; Wang, Kai; Ellis, Stephen G; Chen, Qiuyun; Topol, Eric J; Wang, Qing K

    2014-01-01

    Coronary artery disease (CAD) is the leading cause of death worldwide. Recent genome-wide association studies (GWAS) identified >50 common variants associated with CAD or its complication myocardial infarction (MI), but collectively they account for missing heritability". Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL) analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL  = 5.49) and 3q29 (NPL  = 6.84). We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL  = 3.18-4.07). These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.

  15. QTL IciMapping:Integrated software for genetic linkage map construction and quantitative trait locus mapping in biparental populations

    Institute of Scientific and Technical Information of China (English)

    Lei; Meng; Huihui; Li; Luyan; Zhang; Jiankang; Wang

    2015-01-01

    QTL Ici Mapping is freely available public software capable of building high-density linkage maps and mapping quantitative trait loci(QTL) in biparental populations. Eight functionalities are integrated in this software package:(1) BIN: binning of redundant markers;(2) MAP: construction of linkage maps in biparental populations;(3) CMP: consensus map construction from multiple linkage maps sharing common markers;(4) SDL: mapping of segregation distortion loci;(5) BIP: mapping of additive, dominant, and digenic epistasis genes;(6) MET: QTL-by-environment interaction analysis;(7) CSL: mapping of additive and digenic epistasis genes with chromosome segment substitution lines; and(8) NAM: QTL mapping in NAM populations. Input files can be arranged in plain text, MS Excel 2003, or MS Excel 2007 formats. Output files have the same prefix name as the input but with different extensions. As examples, there are two output files in BIN, one for summarizing the identified bin groups and deleted markers in each bin, and the other for using the MAP functionality. Eight output files are generated by MAP, including summary of the completed linkage maps, Mendelian ratio test of individual markers, estimates of recombination frequencies, LOD scores, and genetic distances, and the input files for using the BIP, SDL,and MET functionalities. More than 30 output files are generated by BIP, including results at all scanning positions, identified QTL, permutation tests, and detection powers for up to six mapping methods. Three supplementary tools have also been developed to display completed genetic linkage maps, to estimate recombination frequency between two loci,and to perform analysis of variance for multi-environmental trials.

  16. QTL IciMapping:Integrated software for genetic linkage map construction and quantitative trait locus mapping in biparental populations

    Institute of Scientific and Technical Information of China (English)

    Lei Meng; Huihui Li; Luyan Zhang; Jiankang Wang

    2015-01-01

    QTL IciMapping is freely available public software capable of building high-density linkage maps and mapping quantitative trait loci (QTL) in biparental populations. Eight func-tionalities are integrated in this software package: (1) BIN:binning of redundant markers;(2) MAP: construction of linkage maps in biparental populations; (3) CMP: consensus map construction from multiple linkage maps sharing common markers; (4) SDL: mapping of segregation distortion loci;(5) BIP:mapping of additive, dominant, and digenic epistasis genes;(6) MET:QTL-by-environment interaction analysis;(7) CSL:mapping of additive and digenic epistasis genes with chromosome segment substitution lines; and (8) NAM: QTL mapping in NAM populations. Input files can be arranged in plain text, MS Excel 2003, or MS Excel 2007 formats. Output files have the same prefix name as the input but with different extensions. As examples, there are two output files in BIN, one for summarizing the identified bin groups and deleted markers in each bin, and the other for using the MAP functionality. Eight output files are generated by MAP, including summary of the completed linkage maps, Mendelian ratio test of individual markers, estimates of recombination frequencies, LOD scores, and genetic distances, and the input files for using the BIP, SDL, and MET functionalities. More than 30 output files are generated by BIP, including results at all scanning positions, identified QTL, permutation tests, and detection powers for up to six mapping methods. Three supplementary tools have also been developed to display completed genetic linkage maps, to estimate recombination frequency between two loci, and to perform analysis of variance for multi-environmental trials.

  17. QTL IciMapping: Integrated software for genetic linkage map construction and quantitative trait locus mapping in biparental populations

    Directory of Open Access Journals (Sweden)

    Lei Meng

    2015-06-01

    Full Text Available QTL IciMapping is freely available public software capable of building high-density linkage maps and mapping quantitative trait loci (QTL in biparental populations. Eight functionalities are integrated in this software package: (1 BIN: binning of redundant markers; (2 MAP: construction of linkage maps in biparental populations; (3 CMP: consensus map construction from multiple linkage maps sharing common markers; (4 SDL: mapping of segregation distortion loci; (5 BIP: mapping of additive, dominant, and digenic epistasis genes; (6 MET: QTL-by-environment interaction analysis; (7 CSL: mapping of additive and digenic epistasis genes with chromosome segment substitution lines; and (8 NAM: QTL mapping in NAM populations. Input files can be arranged in plain text, MS Excel 2003, or MS Excel 2007 formats. Output files have the same prefix name as the input but with different extensions. As examples, there are two output files in BIN, one for summarizing the identified bin groups and deleted markers in each bin, and the other for using the MAP functionality. Eight output files are generated by MAP, including summary of the completed linkage maps, Mendelian ratio test of individual markers, estimates of recombination frequencies, LOD scores, and genetic distances, and the input files for using the BIP, SDL, and MET functionalities. More than 30 output files are generated by BIP, including results at all scanning positions, identified QTL, permutation tests, and detection powers for up to six mapping methods. Three supplementary tools have also been developed to display completed genetic linkage maps, to estimate recombination frequency between two loci, and to perform analysis of variance for multi-environmental trials.

  18. Linkage and candidate gene studies of autism spectrum disorders in European populations

    Science.gov (United States)

    Holt, Richard; Barnby, Gabrielle; Maestrini, Elena; Bacchelli, Elena; Brocklebank, Denise; Sousa, Inês; Mulder, Erik J; Kantojärvi, Katri; Järvelä, Irma; Klauck, Sabine M; Poustka, Fritz; Bailey, Anthony J; Monaco, Anthony P

    2010-01-01

    Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate previously reported associations. In this paper, we investigate previously implicated genomic regions for a role in ASD susceptibility, using four cohorts of European ancestry. Initially, a 384 SNP Illumina GoldenGate array was used to examine linkage at six previously implicated loci. We identify linkage approaching genome-wide suggestive levels on chromosome 2 (rs2885116, MLOD=1.89). Association analysis showed significant associations in MKL2 with ASD (rs756472, P=4.31 × 10−5) and between SND1 and strict autism (rs1881084, P=7.76 × 10−5) in the Finnish and Northern Dutch populations, respectively. Subsequently, we used a second 384 SNP Illumina GoldenGate array to examine the association in seven candidate genes, and evidence for association was found in RELN (rs362780, P=0.00165). Further increasing the sample size strengthened the association with RELN (rs362780, P=0.001) and produced a second significant result in GRIK2 (rs2518261, P=0.008). Our results strengthen the case for a more detailed study of the role of RELN and GRIK2 in autism susceptibility, as well as identifying two new potential candidate genes, MKL2 and SND1. PMID:20442744

  19. A Genetic Linkage Map of Brassica rapa Based on AFLP Markers

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jian-jun; WANG Xiao-wu; Guusje Bonnema; SUN Ri-fei; XU Ze-yong; Dick Vreugdenhi; Maarten Koornneef

    2005-01-01

    A F2 mapping population was developed by crossing a Chinese cabbage-pe-tsai variety CC156 and an oil type Rapid cycling RC144 which were different from each other in morphology, maturity, self-compatibility, plant height, etc. Using 244 AFLP markers a map was constructed containing 10 main linkage groups covering a total distance of 857 cM,corresponding to 3.5 cM per marker. Length of linkage groups varied from 43 to 125 cM and the number of AFLP markers linkage to each group ranged from 7 to 41.

  20. THREaD Mapper Studio: a novel, visual web server for the estimation of genetic linkage maps.

    Science.gov (United States)

    Cheema, Jitender; Ellis, T H Noel; Dicks, Jo

    2010-07-01

    The estimation of genetic linkage maps is a key component in plant and animal research, providing both an indication of the genetic structure of an organism and a mechanism for identifying candidate genes associated with traits of interest. Because of this importance, several computational solutions to genetic map estimation exist, mostly implemented as stand-alone software packages. However, the estimation process is often largely hidden from the user. Consequently, problems such as a program crashing may occur that leave a user baffled. THREaD Mapper Studio (http://cbr.jic.ac.uk/threadmapper) is a new web site that implements a novel, visual and interactive method for the estimation of genetic linkage maps from DNA markers. The rationale behind the web site is to make the estimation process as transparent and robust as possible, while also allowing users to use their expert knowledge during analysis. Indeed, the 3D visual nature of the tool allows users to spot features in a data set, such as outlying markers and potential structural rearrangements that could cause problems with the estimation procedure and to account for them in their analysis. Furthermore, THREaD Mapper Studio facilitates the visual comparison of genetic map solutions from third party software, aiding users in developing robust solutions for their data sets.

  1. Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9

    Directory of Open Access Journals (Sweden)

    Loy Clement T

    2008-08-01

    Full Text Available Abstract Background Frontotemporal lobar degeneration (FTLD represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD and motor neuron disease (MND. The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Methods Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Results Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Conclusion Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease

  2. 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...... Findings: For the entire set of 379 GGE-multiplex families, linkage analysis revealed six loci achieving suggestive evidence for linkage at 1p36.22, 3p14.2, 5q34, 13q12.12, 13q31.3, and 19q13.42. The linkage finding at 5q34 was consistently supported by both NPL and parametric linkage results across all...

  3. Genetic variation, population structure, and linkage disequilibrium in European elite germplasm of perennial ryegrass

    DEFF Research Database (Denmark)

    Brazauskas, Gintaras; Lenk, Ingo; Pedersen, Morten Greve;

    2011-01-01

    Perennial ryegrass (Lolium perenne L.) is a highly valued temperate climate grass species grown as forage crop and for amenity uses. Due to its outbreeding nature and recent domestication, a high degree of genetic diversity is expected among cultivars. The aim of this study was to assess the exte...

  4. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteracaea)

    NARCIS (Netherlands)

    Vijverberg, K.; Hulst, van der R.G.M.; Lindhout, W.H.; Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  5. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae)

    NARCIS (Netherlands)

    Vijverberg, Kitty; van der Hulst, R.G.M.; Lindhout, P.; Van Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  6. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteracaea)

    NARCIS (Netherlands)

    Vijverberg, K.; Hulst, van der R.G.M.; Lindhout, W.H.; Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  7. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae)

    NARCIS (Netherlands)

    Vijverberg, Kitty; van der Hulst, R.G.M.; Lindhout, P.; Van Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  8. Refined mapping of the gene causing Familial Mediterranean fever, by linkage and homozygosity studies

    Energy Technology Data Exchange (ETDEWEB)

    Aksentijevich, I.; Pras, E.; Gruberg, L.; Helling, S.; Prosen, L.; Pras, M.; Kastner, D.L. (National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD (United States)); Shen, Y.; Holman, K.; Sutherland, G.R.; Richards, R.I. (Adelaide Children' s Hospital (Australia)); Ramsburg, M.; Dean, M. (Laboratory of Viral Carcinogenesis, Frederick, MD (United States)); Amos, C.I. (Laboratory of Skin Biology, Bethesda, MD (United States))

    1993-08-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. The authors recently reported linkage of the gene causing FMF (designated [open quotes]MEF[close quotes]) to two markers on chromosome 16p. To map MEF more precisely, they have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. They also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location. 30 refs., 6 figs., 2 tabs.

  9. Population genetic structure, linkage disequilibrium and effective population size of conserved and extensively raised village chicken populations of Southern Africa.

    Science.gov (United States)

    Khanyile, Khulekani S; Dzomba, Edgar F; Muchadeyi, Farai C

    2015-01-01

    Extensively raised village chickens are considered a valuable source of biodiversity, with genetic variability developed over thousands of years that ought to be characterized and utilized. Surveys that can reveal a population's genetic structure and provide an insight into its demographic history will give valuable information that can be used to manage and conserve important indigenous animal genetic resources. This study reports population diversity and structure, linkage disequilibrium and effective population sizes of Southern African village chickens and conservation flocks from South Africa. DNA samples from 312 chickens from South African village and conservation flocks (n = 146), Malawi (n = 30) and Zimbabwe (n = 136) were genotyped using the Illumina iSelect chicken SNP60K BeadChip. Population genetic structure analysis distinguished the four conservation flocks from the village chicken populations. Of the four flocks, the Ovambo clustered closer to the village chickens particularly those sampled from South Africa. Clustering of the village chickens followed a geographic gradient whereby South African chickens were closer to those from Zimbabwe than to chickens from Malawi. Different conservation flocks seemed to have maintained different components of the ancestral genomes with a higher proportion of village chicken diversity found in the Ovambo population. Overall population LD averaged over chromosomes ranged from 0.03 ± 0.07 to 0.58 ± 0.41 and averaged 0.15 ± 0.16. Higher LD, ranging from 0.29 to 0.36, was observed between SNP markers that were less than 10 kb apart in the conservation flocks. LD in the conservation flocks steadily decreased to 0.15 (PK) and 0.24 (VD) at SNP marker interval of 500 kb. Genomewide LD decay in the village chickens from Malawi, Zimbabwe and South Africa followed a similar trend as the conservation flocks although the mean LD values for the investigated SNP intervals were lower. The results suggest low effective

  10. Linkage analysis and map construction in genetic populations of clonal F1 and double cross.

    Science.gov (United States)

    Zhang, Luyan; Li, Huihui; Wang, Jiankang

    2015-01-15

    In this study, we considered four categories of molecular markers based on the number of distinguishable alleles at the marker locus and the number of distinguishable genotypes in clonal F1 progenies. For two marker loci, there are nine scenarios that allow the estimation of female, male, and/or combined recombination frequencies. In a double cross population derived from four inbred lines, five categories of markers are classified and another five scenarios are present for recombination frequency estimation. Theoretical frequencies of identifiable genotypes were given for each scenario, from which the maximum likelihood estimates of one or more of the three recombination frequencies could be estimated. If there was no analytic solution, then Newton-Raphson method was used to acquire a numerical solution. We then proposed to use an algorithm in Traveling Salesman Problem to determine the marker order. Finally, we proposed a procedure to build the two haploids of the female parent and the two haploids of the male parent in clonal F1. Once the four haploids were built, clonal F1 hybrids could be exactly regarded as a double cross population. Efficiency of the proposed methods was demonstrated in simulated clonal F1 populations and one actual maize double cross. Extensive comparisons with software JoinMap4.1, OneMap, and R/qtl show that the methodology proposed in this article can build more accurate linkage maps in less time.

  11. The first genetic linkage map of Primulina eburnea (Gesneriaceae) based on EST-derived SNP markers.

    Science.gov (United States)

    Feng, Chen; Feng, Chao; Kang, Ming

    2016-06-01

    Primulina eburnea is a promising candidate for domestication and floriculture, since it is easy to culture and has beautiful flowers. An F₂ population of 189 individuals was established for the construction of first-generation linkage maps based on expressed sequence tags-derived single-nucleotide polymorphism markers using the massARRAY genotyping platform. Of the 232 screened markers, 215 were assigned to 18 LG according to the haploid number of chromosomes in the species. The linkage map spanned a total of 3774.7 cM with an average distance of 17.6 cM between adjacent markers. This linkage map provides a framework for identification of important genes in breeding programmes.

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

    Science.gov (United States)

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

    2016-06-01

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

  13. Chinese Xibe population genetic composition according to linkage groups of X-chromosomal STRs: population genetic variability and interpopulation comparisons.

    Science.gov (United States)

    Meng, Hao-Tian; Shen, Chun-Mei; Zhang, Yu-Dang; Dong, Qian; Guo, Yu-Xin; Yang, Guang; Yan, Jiang-Wei; Liu, Yao-Shun; Mei, Ting; Shi, Jian-Feng; Zhu, Bo-Feng

    2017-09-01

    The Xibe population is one of China's officially recognised populations and is now distributed separately from west to east in the northern part of China. X-chromosomal short tandem repeats have a special inheritance pattern, and could be used as complements in forensic application, especially for complex or deficiency cases. This study obtained the allelic and haplotypic frequencies of 19 X-STR loci in the Xibe population from Xinjiang Uygur Autonomous Region, China, and studied the genetic differentiations between the Xibe and other populations. The combined power of discrimination in females and males and mean exclusion chances in deficiency cases, normal trios and duo cases was at least 0.999 999 994. In the haplotypic study, the Xibe population showed a more similar pattern of haplotype distribution with Asian populations than populations from other continents, while allelic study also indicated a closer relationship between the Xibe and Asian populations. The 19 X-STR loci would be useful in forensic application in the studied population. The Xibe population showed a closer genetic relationship with Asian populations in the study, and more population data would be necessary for more detailed genetic relationship studies.

  14. An expanded genetic linkage map of an intervarietal Agaricus bisporus var. bisporusxA. bisporus var. burnettii hybrid based on AFLP, SSR and CAPS markers sheds light on the recombination behaviour of the species.

    Science.gov (United States)

    Foulongne-Oriol, Marie; Spataro, Cathy; Cathalot, Vincent; Monllor, Sarah; Savoie, Jean-Michel

    2010-03-01

    A genetic linkage map for the edible basidiomycete Agaricus bisporus was constructed from 118 haploid homokaryons derived from an intervarietal A. bisporus var. bisporus x A. bisporus var. burnettii hybrid. Two hundred and thirty-one AFLP, 21 SSR, 68 CAPS markers together with the MAT, BSN, PPC1 loci and one allozyme locus (ADH) were evenly spread over 13 linkage groups corresponding to the chromosomes of A. bisporus. The map covers 1156cM, with an average marker spacing of 3.9cM and encompasses nearly the whole genome. The average number of crossovers per chromosome per individual is 0.86. Normal recombination over the entire genome occurs in the heterothallic variety, burnettii, contrary to the homothallic variety, bisporus, which showed adaptive genome-wide suppressed recombination. This first comprehensive genetic linkage map for A. bisporus provides foundations for quantitative trait analyses and breeding programme monitoring, as well as genome organisation studies.

  15. Genome-wide linkage scan identifies two novel genetic loci for coronary artery disease: in GeneQuest families.

    Directory of Open Access Journals (Sweden)

    Hanxiang Gao

    Full Text Available Coronary artery disease (CAD is the leading cause of death worldwide. Recent genome-wide association studies (GWAS identified >50 common variants associated with CAD or its complication myocardial infarction (MI, but collectively they account for <20% of heritability, generating a phenomena of "missing heritability". Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL  = 5.49 and 3q29 (NPL  = 6.84. We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL  = 3.18-4.07. These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.

  16. Development of a molecular genetic linkage map for Colletotrichum lindemuthianum and segregation analysis of two avirulence genes.

    Science.gov (United States)

    Luna-Martínez, Francisco; Rodríguez-Guerra, Raúl; Victoria-Campos, Mayra; Simpson, June

    2007-02-01

    A framework genetic map was developed for the fungal pathogen Colletotrichum lindemuthianum, the causal agent of anthracnose of common bean (Phaseolus vulgaris L.). This is the first genetic map for any species within the family Melanconiaceae and the genus Colletotrichum and provides the first estimate of genome length for C. lindemuthianum. The map was generated using 106 haploid F1 progeny derived from crossing two Mexican C. lindemuthianum isolates differing in two avirulence genes (AvrclMex and AvrclTO). The map comprises 165 AFLP markers covering 1,897 cM with an average spacing of 11.49 cM. The markers are distributed over 19 major linkage groups containing between 5 and 25 markers each and the genome length was estimated to be approximately 3,241 cM. The avirulence genes AvrclMex and AvrclTO segregate in a 1:1 ratio supporting the gene for gene hypothesis for the incompatible reaction between C. lindemuthianum and P. vulgaris, but could not be incorporated into the genetic map. This initial outline map forms the basis for the development of a more detailed C. lindemuthianum linkage map, which would include other types of molecular markers and allow the location of genes previously isolated and characterized in this species.

  17. The genetic differences with whole genome linkage disequilibrium mapping between responder and non-responder in interferon-alpha and ribavirin combined therapy for chronic hepatitis C patients.

    Science.gov (United States)

    Chen, P-J; Hwang, Y; Lin, C G-J; Wu, Y-J; Wu, L S-H

    2008-04-01

    Interferon-alpha and ribavirin combined therapy has been a mainstream treatment for hepatitis C infection. The efficacy of this combined treatment is around 30% to 60%, and the factors affecting the responsiveness are still poorly defined. Our study is intended to investigate the genetic differences between responder and non-responder patients. The genome-wide linkage disequilibrium screening for loci associated with genetic difference between two patient groups was conducted by using 382 autosomal short tandem repeat (STR) markers involving 92 patients. We have identified 19 STR markers displaying different allele frequencies between the two patient groups. In addition, based on their genomic location and biological function, we selected the CD81 and IL15 genes to perform single nucleotide polymorphism genotyping. In conclusion, this study may provide a new approach for identifying the associated polymorphisms and the susceptible loci for interferon-alpha and ribavirin combined therapy in patients with chronic hepatitis C.

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

    Directory of Open Access Journals (Sweden)

    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

  19. Optimizing linkage and retention to hypertension care in rural Kenya (LARK hypertension study): study protocol for a randomized controlled trial

    National Research Council Canada - National Science Library

    Vedanthan, Rajesh; Kamano, Jemima H; Naanyu, Violet; Delong, Allison K; Were, Martin C; Finkelstein, Eric A; Menya, Diana; Akwanalo, Constantine O; Bloomfield, Gerald S; Binanay, Cynthia A; Velazquez, Eric J; Hogan, Joseph W; Horowitz, Carol R; Inui, Thomas S; Kimaiyo, Sylvester; Fuster, Valentin

    2014-01-01

    .... This study investigates whether community health workers, equipped with a tailored behavioral communication strategy and smartphone technology, can increase linkage and retention of hypertensive...

  20. Physical mapping of 49 microsatellite markers on chromosome 19 and correlation with the genetic linkage map

    Energy Technology Data Exchange (ETDEWEB)

    Reguigne-Arnould, I.; Mollicone, R.; Candelier, J.J. [INSERM, Villejuif (France)] [and others

    1996-03-05

    We have regionally localized 49 microsatellite markers developed by Genethon using a panel of previously characterized somatic cell hybrids that retain fragments from chromosome 19. The tight correlation observed between the physical and the genetic orders of the microsatellites provide cytogenetic anchorages to the genetic map data. We propose a position for the centromere just above D19S415, from the study of two hybrids, each of which retains one of the two derivatives of a balanced translocation t(1;19)(q11;q11). Microsatellites, which can be identified by a standard PCR protocol, are useful tools for the localization of disease genes and for the establishment of YAC or cosmid contigs. These markers can also judiciously be used for the characterization of new hybrid cell line panels. We report such a characterization of 11 clones, 8 of which were obtained by irradiation-fusion. Using the whole hybrid panel, we were able to define the order of 12 pairs of genetically colocalized microsatellites. As examples of gene mapping by the combined use of microsatellites and hybrid cell lines, we regionally assigned the PVS locus between the 19q13.2 markers D19S417 and D19S423 and confirmed the locations of fucosyltransferase loci FUT1, FUT2, and FUT5. 13 refs., 1 fig.

  1. Genetic Diversity, Population Structure, and Linkage Disequilibrium of an Association-Mapping Panel Revealed by Genome-Wide SNP Markers in Sesame

    Science.gov (United States)

    Cui, Chengqi; Mei, Hongxian; Liu, Yanyang; Zhang, Haiyang; Zheng, Yongzhan

    2017-01-01

    The characterization of genetic diversity and population structure can be used in tandem to detect reliable phenotype–genotype associations. In the present study, we genotyped a set of 366 sesame germplasm accessions by using 89,924 single-nucleotide polymorphisms (SNPs). The number of SNPs on each chromosome was consistent with the physical length of the respective chromosome, and the average marker density was approximately 2.67 kb/SNP. The genetic diversity analysis showed that the average nucleotide diversity of the panel was 1.1 × 10-3, with averages of 1.0 × 10-4, 2.7 × 10-4, and 3.6 × 10-4 obtained, respectively for three identified subgroups of the panel: Pop 1, Pop 2, and the Mixed. The genetic structure analysis revealed that these sesame germplasm accessions were structured primarily along the basis of their geographic collection, and that an extensive admixture occurred in the panel. The genome-wide linkage disequilibrium (LD) analysis showed that an average LD extended up to ∼99 kb. The genetic diversity and population structure revealed in this study should provide guidance to the future design of association studies and the systematic utilization of the genetic variation characterizing the sesame panel. PMID:28729877

  2. A genome-wide linkage analysis for the personality trait neuroticism in the Irish affected sib-pair study of alcohol dependence.

    Science.gov (United States)

    Kuo, Po-Hsiu; Neale, Michael C; Riley, Brien P; Patterson, Diana G; Walsh, Dermot; Prescott, Carol A; Kendler, Kenneth S

    2007-06-05

    Neuroticism is a personality trait which reflects individual differences in emotional stability and vulnerability to stress and anxiety. Consistent evidence shows substantial genetic influences on variation in this trait. The present study seeks to identify regions containing susceptibility loci for neuroticism using a selected sib-pair sample from Ireland. Using Merlin regress, we conducted a 4 cM whole-genome linkage analysis on 714 sib-pairs. Evidence for linkage to neuroticism was found on chromosomes 11p, 12q, and 15q. The highest linkage peak was on 12q at marker D12S1638 with a Lod score of 2.13 (-log p = 2.76, empirical P-value neuroticism, with male specific linkage regions on chromosomes 1, 4, 11, 12, 15, 16, and 22, and female specific linkage regions on chromosomes 2, 4, 9, 12, 13, and 18. Some genome regions reported in the present study replicate findings from previous linkage studies of neuroticism. These results, together with prior studies, indicate several potential regions for quantitative trait loci for neuroticism that warrant further study.

  3. The first genetic linkage map of Primulina eburnea (Gesneriaceae) based on EST-derived SNP marker

    Indian Academy of Sciences (India)

    CHEN FENG; CHAO FENG; MING KANG

    2016-06-01

    Primulina eburneais a promising candidate for domestication and floriculture, since it is easy to culture and has beautiful flow-ers. An F2population of 189 individuals was established for the construction of first-generation linkage maps based onexpressed sequence tags-derived single-nucleotide polymorphism markers using the massARRAY genotyping platform. Ofthe 232 screened markers, 215 were assigned to 18 LG according to the haploid number of chromosomes in the species. Thelinkage map spanned a total of 3774.7 cM with an average distance of 17.6 cM between adjacent markers. This linkage mapprovides a framework for identification of important genes in breeding programm

  4. High-density linkage maps fail to detect any genetic component to sex determination in a Rana temporaria family.

    Science.gov (United States)

    Brelsford, A; Rodrigues, N; Perrin, N

    2016-01-01

    Sex chromosome differentiation in Rana temporaria varies strikingly among populations or families: whereas some males display well-differentiated Y haplotypes at microsatellite markers on linkage group 2 (LG2), others are genetically undistinguishable from females. We analysed with RADseq markers one family from a Swiss lowland population with no differentiated sex chromosomes, and where sibship analyses had failed to detect any association between the phenotypic sex of progeny and parental haplotypes. Offspring were reared in a common tank in outdoor conditions and sexed at the froglet stage. We could map a total of 2177 SNPs (1123 in the mother, 1054 in the father), recovering in both adults 13 linkage groups (= chromosome pairs) that were strongly syntenic to Xenopus tropicalis despite > 200 My divergence. Sexes differed strikingly in the localization of crossovers, which were uniformly distributed in the female but limited to chromosome ends in the male. None of the 2177 markers showed significant association with offspring sex. Considering the very high power of our analysis, we conclude that sex determination was not genetic in this family; which factors determined sex remain to be investigated.

  5. Genetic mapping of the gene for Usher syndrome: Linkage analysis in a large Samaritan kindred

    Energy Technology Data Exchange (ETDEWEB)

    Bonne-Tamir, B.; Korostishevsky, M.; Kalinsky, H.; Seroussi, E.; Beker, R.; Weiss, S. (Sackler Faculty of Medicine, Ramat-Aviv (Israel)); Godel, V. (Ichilov Hospital, Tel-Aviv (Israel))

    1994-03-01

    Usher syndrome is a group of autosomal recessive disorders associated with congenital sensorineural deafness and progressive visual loss due to retinitis pigmentosa. Sixteen members of the small inbred Samaritan isolate with autosomal recessive deafness from 59 individuals including parents and affected and nonaffected sibs were typed for markers on chromosomes 1q and 11q for which linkage has recently been established for Usher syndrome types II and I. Statistically significant linkage was observed with four markers on 11q (D11S533, D11S527, OMP, and INT2) with a maximum six-point location score of 11.61 at the D11S533 locus. Analysis of haplotypes supports the notion that the mutation arose only once in an ancestral chromosome carrying a specific haplotype. The availability of markers closely linked to the disease locus allows indirect genotype analysis and identifies all carriers of the gene within the community. Furthermore, the detection of complete linkage disequilibrium between the D11S533 marker and the Usher gene suggests that these loci are either identical or adjacent and narrows the critical region to which physical mapping efforts are currently directed. 35 refs., 2 figs., 6 tabs.

  6. Genetical control and linkage relationships of isozyme markers in sugar beet (B. vulgaris L.) : 1. Isocitrate dehydrogenase, adenylate kinase, phosphoglucomutase, glucose phosphate isomerase and cathodal peroxidase.

    Science.gov (United States)

    Smed, E; Van Geyt, J P; Oleo, M

    1989-07-01

    Five isozyme systems were genetically investigated. The different separation techniques, the developmental expression and the use as marker system in sugar beet genetics and breeding is discussed. Isocitrate dehydrogenase was controlled by two genes. The gene products form inter- as well as intralocus dimers, even with the gene products of the Icd gene in B. procumbens and B. patellaris. Adenylate kinase was controlled by one gene. Three different allelic forms were detected, which were active as monomeric proteins. Glucose phosphate isomerase showed two zones of activity. One zone was polymorphic. Three allelic variants, active as dimers, were found. Phosphoglucomutase also showed two major zones of activity. One zone was polymorphic and coded for monomeric enzymes. Two allelic forms were found in the accessions studied. The cathodal peroxidase system was controlled by two independent genes, of which only one was polymorphic. The gene products are active as monomers. Linkage was found between red hypocotyl color (R) and Icd 2. Pgm 1, Gpi 2, Ak 1 and the Icd 2-R linkage group segregated independently.

  7. A wheat intervarietal genetic linkage map based on microsatellite and target region amplified polymorphism markers and its utility for detecting quantitative trait loci.

    Science.gov (United States)

    Liu, Z H; Anderson, J A; Hu, J; Friesen, T L; Rasmussen, J B; Faris, J D

    2005-08-01

    Efficient user-friendly methods for mapping plant genomes are highly desirable for the identification of quantitative trait loci (QTLs), genotypic profiling, genomic studies, and marker-assisted selection. SSR (microsatellite) markers are user-friendly and efficient in detecting polymorphism, but they detect few loci. Target region amplification polymorphism (TRAP) is a relatively new PCR-based technique that detects a large number of loci from a single reaction without extensive pre-PCR processing of samples. In the investigation reported here, we used both SSRs and TRAPs to generate over 700 markers for the construction of a genetic linkage map in a hard red spring wheat intervarietal recombinant inbred population. A framework map consisting of 352 markers accounted for 3,045 cM with an average density of one marker per 8.7 cM. On average, SSRs detected 1.9 polymorphic loci per reaction, while TRAPs detected 24. Both marker systems were suitable for assigning linkage groups to chromosomes using wheat aneuploid stocks. We demonstrated the utility of the maps by identifying major QTLs for days to heading and reduced plant height on chromosomes 5A and 4B, respectively. Our results indicate that TRAPs are highly efficient for genetic mapping in wheat. The maps developed will be useful for the identification of quality and disease resistance QTLs that segregate in this population.

  8. Combined Linkage and Association Studies Show that HLA Class II Variants Control Levels of Antibodies against Epstein-Barr Virus Antigens

    OpenAIRE

    Vincent Pedergnana; Laurène Syx; Aurélie Cobat; Julien Guergnon; Pauline Brice; Christophe Fermé; Patrice Carde; Olivier Hermine; Catherine Le-Pendeven; Corinne Amiel; Yassine Taoufik; Alexandre Alcaïs; Ioannis Theodorou; Caroline Besson; Laurent Abel

    2014-01-01

    Over 95% of the adult population worldwide is infected with Epstein-Barr virus (EBV). EBV infection is associated with the development of several cancers, including Hodgkin lymphoma (HL). Elevated levels of anti-EBV antibodies have been associated with increased risk of HL. There is growing evidence that genetic factors control the levels of antibodies against EBV antigens. Here, we conducted linkage and association studies to search for genetic factors influencing either anti-viral capsid an...

  9. Meta-analysis of genome-wide linkage studies across autoimmune diseases

    Science.gov (United States)

    Forabosco, Paola; Bouzigon, Emmanuelle; Ng, Mandy Y; Hermanowski, Jane; Fisher, Sheila A; Criswell, Lindsey A; Lewis, Cathryn M

    2009-01-01

    Autoimmune diseases are chronic disorders initiated by a loss of immunologic tolerance to self-antigens. They cluster within families, and patients may be diagnosed with more than one disease, suggesting pleiotropic genes are involved in the aetiology of different diseases. To identify potential loci, which confer susceptibility to autoimmunity independent of disease phenotype, we pooled results from genome-wide linkage studies, using the genome scan meta-analysis method (GSMA). The meta-analysis included 42 independent studies for 11 autoimmune diseases, using 7350 families with 18 291 affected individuals. In addition to the HLA region, which showed highly significant genome-wide evidence for linkage, we obtained suggestive evidence for linkage on chromosome 16, with peak evidence at 10.0–19.8 Mb. This region may harbour a pleiotropic gene (or genes) conferring risk for several diseases, although no such gene has been identified through association studies. We did not identify evidence for linkage at several genes known to confer increased risk to different autoimmune diseases (PTPN22, CTLA4), even in subgroups of diseases consistently found to be associated with these genes. The relative risks conferred by variants in these genes are modest (<1.5 in most cases), and even a large study like this meta-analysis lacks power to detect linkage. This study illustrates the concept that linkage and association studies have power to identify very different types of disease-predisposing variants. PMID:18781189

  10. Cytogenetic characterization and AFLP-based genetic linkage mapping for the butterfly Bicyclus anynana, covering all 28 karyotyped chromosomes.

    Directory of Open Access Journals (Sweden)

    Arjen E Van't Hof

    Full Text Available BACKGROUND: The chromosome characteristics of the butterfly Bicyclus anynana, have received little attention, despite the scientific importance of this species. This study presents the characterization of chromosomes in this species by means of cytogenetic analysis and linkage mapping. METHODOLOGY/PRINCIPAL FINDINGS: Physical genomic features in the butterfly B. anynana were examined by karyotype analysis and construction of a linkage map. Lepidoptera possess a female heterogametic W-Z sex chromosome system. The WZ-bivalent in pachytene oocytes of B. anynana consists of an abnormally small, heterochromatic W-chromosome with the Z-chromosome wrapped around it. Accordingly, the W-body in interphase nuclei is much smaller than usual in Lepidoptera. This suggests an intermediate stage in the process of secondary loss of the W-chromosome to a ZZ/Z sex determination system. Two nucleoli are present in the pachytene stage associated with an autosome and the WZ-bivalent respectively. Chromosome counts confirmed a haploid number of n = 28. Linkage mapping had to take account of absence of crossing-over in females, and of our use of a full-sib crossing design. We developed a new method to determine and exclude the non-recombinant uninformative female inherited component in offspring. The linkage map was constructed using a novel approach that uses exclusively JOINMAP-software for Lepidoptera linkage mapping. This approach simplifies the mapping procedure, avoids over-estimation of mapping distance and increases the reliability of relative marker positions. A total of 347 AFLP markers, 9 microsatellites and one single-copy nuclear gene covered all 28 chromosomes, with a mapping distance of 1354 cM. Conserved synteny of Tpi on the Z-chromosome in Lepidoptera was confirmed for B. anynana. The results are discussed in relation to other mapping studies in Lepidoptera. CONCLUSIONS/SIGNIFICANCE: This study adds to the knowledge of chromosome structure and

  11. Association between cancer and contact allergy: a linkage study

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Thyssen, Jacob P; Menné, Torkil

    2011-01-01

    and cancer, few have looked into the association between cancer and contact allergy, a type IV allergy. By linking two clinical databases, the authors investigate the possible association between contact allergy and cancer. Methods Record linkage of two different registers was performed: (1) a tertiary...... hospital register of dermatitis patients patch tested for contact allergy and (2) a nationwide cancer register (the Danish Cancer Register). After linking the two registers, only cancer subtypes with 40 or more patients registered were included in the analysis. The final associations were evaluated...... by logistic regression analysis. Results An inverse association between contact allergy and non-melanoma skin- and breast cancer, respectively, was identified in both sexes, and an inverse trend for brain cancer was found in women with contact allergy. Additionally, a positive association between contact...

  12. Association between cancer and contact allergy: a linkage study

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Thyssen, Jacob P; Menné, Torkil

    2011-01-01

    hospital register of dermatitis patients patch tested for contact allergy and (2) a nationwide cancer register (the Danish Cancer Register). After linking the two registers, only cancer subtypes with 40 or more patients registered were included in the analysis. The final associations were evaluated...... by logistic regression analysis. Results An inverse association between contact allergy and non-melanoma skin- and breast cancer, respectively, was identified in both sexes, and an inverse trend for brain cancer was found in women with contact allergy. Additionally, a positive association between contact...... and cancer, few have looked into the association between cancer and contact allergy, a type IV allergy. By linking two clinical databases, the authors investigate the possible association between contact allergy and cancer. Methods Record linkage of two different registers was performed: (1) a tertiary...

  13. Genetic linkage mapping of the dehydroepiandrosterone sulfotransferase (STD) gene on the chromosome 19q13.3 region

    Energy Technology Data Exchange (ETDEWEB)

    Durocher, F.; Morissette, J.; Dufort, I.; Simard, J.; Luu-The, V. [Laval Univ. Quebec (Canada)

    1995-10-10

    In the human liver and adrenal, there is a single hydroxysteroid sulfotransferase, which catalyzes the transformation of dehydroepiandrosterone to dehydroepiandrosterone sulfate, the most abundantly circulating steroid in humans, and also catalyzes the sulfation of a series of other 3{beta}-hydroxysteroids as well as cholesterol. Dehydroepiandrosterone sulfate serves as precursor for the formation of active androgens and estrogens in several peripheral tissues, indicating that hydroxysteroid sulfotransferase plays a pivotal role in controlling the hormonal action of sex steroids by regulating their bioavailability. We recently elucidated the structure of the gene encoding hydroxysteroid sulfotransferase (STD), also designated dehydroepiandrosterone sulfotransferase, which spans 17 kb and contains six exons. The STD gene was preliminarily assigned to chromosome 19 by polymerase chain reaction (PCR) amplification of DNA from a panel of human/rodent somatic cell hybrids. To locate the STD gene, the novel biallelic polymorphism found in intron 2 was genotyped in eight CEPH reference families by direct sequencing of PCR products. Two-point linkage analysis was first performed between the latter polymorphism and chromosome 19 markers from Genethon and NIH/CEPH. The closest linkage was observed with D19S412 (Z{sub max} = 9.23; {theta}{sub max} 0.038) and HRC (Z{sub max} =5.95; {theta}{sub max}0.036), located on the 19q13.3 region. A framework map including six Genethon markers flanking the polymorphic STD gene was created by multipoint linkage analysis. Thereafter, a high-resolution genetic map of the region was constructed, yielding to the following order: qter-D19S414-D19S224-D19S420-D19S217-(APOC2-D19S412)-(STD-HRC)-KLK-D19S22-D19S180-PRKCG-D19S418-tel. 24 refs., 2 figs.

  14. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae).

    Science.gov (United States)

    Vijverberg, K; Van Der Hulst, R G M; Lindhout, P; Van Dijk, P J

    2004-02-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The genus includes sexual diploid as well as apomictic polyploid, mostly triploid, plants. Apomictic Taraxacum is diplosporous, parthenogenetic, and has autonomous endosperm formation. Previous studies have indicated that these three apomixis elements are controlled by more than one locus in Taraxacum and that diplospory inherits as a dominant, monogenic trait ( Ddd; DIP). A bulked segregant analysis provided 34 AFLP markers that were linked to DIP and were, together with two microsatellite markers, used for mapping the trait. The map length was 18.6 cM and markers were found on both sides of DIP, corresponding to 5.9 and 12.7 cM, respectively. None of the markers completely co-segregated with DIP. Eight markers were selected for PCR-based marker development, of which two were successfully converted. In contrast to all other mapping studies of apomeiosis to date, our results showed no evidence for suppression of recombination around the DIP locus in Taraxacum. No obvious evidence for sequence divergence between the DIP and non- DIP homologous loci was found, and no hemizygosity at the DIP locus was detected. These results may indicate that apomixis is relatively recent in Taraxacum.

  15. Genetic structure, linkage disequilibrium and association mapping of Verticillium wilt resistance in elite cotton (Gossypium hirsutum L.) germplasm population.

    Science.gov (United States)

    Zhao, Yunlei; Wang, Hongmei; Chen, Wei; Li, Yunhai

    2014-01-01

    Understanding the population structure and linkage disequilibrium in an association panel can effectively avoid spurious associations and improve the accuracy in association mapping. In this study, one hundred and fifty eight elite cotton (Gossypium hirsutum L.) germplasm from all over the world, which were genotyped with 212 whole genome-wide marker loci and phenotyped with an disease nursery and greenhouse screening method, were assayed for population structure, linkage disequilibrium, and association mapping of Verticillium wilt resistance. A total of 480 alleles ranging from 2 to 4 per locus were identified from all collections. Model-based analysis identified two groups (G1 and G2) and seven subgroups (G1a-c, G2a-d), and differentiation analysis showed that subgroup having a single origin or pedigree was apt to differentiate with those having a mixed origin. Only 8.12% linked marker pairs showed significant LD (Pmapping, which widely were distributed among 15 chromosomes. Among which 10 marker loci were found to be consistent with previously identified QTLs and 32 were new unreported marker loci, and QTL clusters for Verticillium wilt resistanc on Chr.16 were also proved in our study, which was consistent with the strong linkage in this chromosome. Our results would contribute to association mapping and supply the marker candidates for marker-assisted selection of Verticillium wilt resistance in cotton.

  16. 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.

  17. Genetic linkage analyses and Cx50 mutation detection in a large multiplex Chinese family with hereditary nuclear cataract.

    Science.gov (United States)

    He, Wei; Li, Xin; Chen, Jiajing; Xu, Ling; Zhang, Feng; Dai, Qiushi; Cui, Hao; Wang, Duen-Mei; Yu, Jun; Hu, Songnian; Lu, Shan

    2011-03-01

    The aim of the study was to characterize the underlying mutation in a large multiplex Chinese family with hereditary nuclear cataract. A 6-generation Chinese family having hereditary nuclear cataract was recruited and clinically verified. Blood DNA samples were obtained from 53 available family members. Linkage analyses were performed on the known candidate regions for hereditary cataract with 36 polymorphic microsatellite markers. To identify mutations related to cataract, a direct sequencing approach was applied to a candidate gene residing in our linkage locus. A linkage locus was identified with a maximum 2-point LOD score of 4.31 (recombination fraction = 0) at marker D1S498 and a maximum multipoint LOD score of 5.7 between markers D1S2344 and D1S498 on chromosome 1q21.1, where the candidate gene Cx50 is located. Direct sequencing of Cx50 showed a 139 G to A transition occurred in all affected family members. This transitional mutation resulted in a replacement of aspartic acid by asparagine at residue 47 (D47N) and led to a loss-of-function of the protein. The D47N mutation of Cx50 causes the hereditary nuclear cataract in this family in an autosomal dominant mode of inheritance with incomplete penetrance.

  18. Linkage studies on Gilles de la Tourette syndrome: what is the strategy of choice?

    Science.gov (United States)

    Heutink, P; van de Wetering, B J; Pakstis, A J; Kurlan, R; Sandor, P; Oostra, B A; Sandkuijl, L A

    1995-08-01

    For a linkage study it is important to ascertain family material that is sufficiently informative. The statistical power of a linkage sample can be determined via computer simulation. For complex traits uncertain parameters such as incomplete penetrance, frequency of phenocopies, gene frequency and variable expression have to be taken into account. One can either include only the most severe phenotype in the analysis or apply multiple linkage tests for a gradually broadened disease phenotype. Gilles de la Tourette syndrome (GTS) is a chronic neurological disorder characterized by multiple, intermittent motor and vocal tics. Segregation analyses suggest that GTS and milder phenotypes are caused by a single dominant gene. We report here the results of an extensive simulation study on a large set of families. We compared the effectiveness of linkage tests with only the GTS phenotype versus multiple tests that included various milder phenotypes and different gene frequencies. The scenario of multiple tests yielded superior power. Our results show that computer simulation can indicate the strategy of choice in linkage studies of multiple, complex phenotypes.

  19. 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.

  20. A sex-averaged genetic linkage map in coastal Douglas-fir (Pseudotsuga menziesii [Mirb] Franco var menziesii) based on RFLP and RAPD markers

    Science.gov (United States)

    K.D. Jermstad; D.L. Bassoni; N.C. Wheeler; D.B. Neale

    1998-01-01

    We have constructed a sex-averaged genetic linkage map in coastal Douglas-fir ( Pseudotsuga menziesii [Mirb.] Franco var menziesii) using a three-generation outcrossed pedigree and molecular markers. Our research objectives are to learn about genome organization and to identify markers associated with adaptive traits. The map...

  1. Construction of Genetic Linkage Map of Bread Wheat (Triticum aestivum L.) Using an Intervarietal Cross and QTL Map for Spike Related Traits

    Institute of Scientific and Technical Information of China (English)

    E. Nalini; S.G. Bhagwat; N. Jawali

    2007-01-01

    @@ Most often a genetic linkage map is prepared using populations obtained from two highly diverse genotypes.However, the markers from such a map may not be useful in a breeding program as these markers may not be polymorphie among the varieties used in breeding.

  2. 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.

  3. A genetic linkage map of willow (Salix viminalis) based on AFLP and microsatelite markers

    NARCIS (Netherlands)

    Hanley, S.; Barker, J.H.A.; Ooijen, van J.W.; Aldam, C.; Harris, S.L.; Ahman, I.; Larsson, S.; Karp, A.

    2002-01-01

    The genus Salix (willow) contains a number of species of great value as biomass crops. Efforts to breed varieties with improved biomass yields and resistances to pests and diseases are limited by the lack of knowledge on the genetic basis of the traits. We have used AFLP and microsatellite markers t

  4. A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage

    DEFF Research Database (Denmark)

    Andersen, Jannik N; Jansen, Peter G; Echwald, Søren M;

    2004-01-01

    and provide predicted amino acid sequences for four human PTPs that are currently defined by fragments only. Finally, we correlated each PTP locus with genetic disease markers and identified 4 PTPs that map to known susceptibility loci for type 2 diabetes and 19 PTPs that map to regions frequently deleted...

  5. A saturated genetic linkage map of autotetraploid alfalfa (Medicago sativa L.) developed using genotyping-by-sequencing is highly syntenous with the Medicago truncatula genome.

    Science.gov (United States)

    Li, Xuehui; Wei, Yanling; Acharya, Ananta; Jiang, Qingzhen; Kang, Junmei; Brummer, E Charles

    2014-08-21

    A genetic linkage map is a valuable tool for quantitative trait locus mapping, map-based gene cloning, comparative mapping, and whole-genome assembly. Alfalfa, one of the most important forage crops in the world, is autotetraploid, allogamous, and highly heterozygous, characteristics that have impeded the construction of a high-density linkage map using traditional genetic marker systems. Using genotyping-by-sequencing (GBS), we constructed low-cost, reasonably high-density linkage maps for both maternal and paternal parental genomes of an autotetraploid alfalfa F1 population. The resulting maps contain 3591 single-nucleotide polymorphism markers on 64 linkage groups across both parents, with an average density of one marker per 1.5 and 1.0 cM for the maternal and paternal haplotype maps, respectively. Chromosome assignments were made based on homology of markers to the M. truncatula genome. Four linkage groups representing the four haplotypes of each alfalfa chromosome were assigned to each of the eight Medicago chromosomes in both the maternal and paternal parents. The alfalfa linkage groups were highly syntenous with M. truncatula, and clearly identified the known translocation between Chromosomes 4 and 8. In addition, a small inversion on Chromosome 1 was identified between M. truncatula and M. sativa. GBS enabled us to develop a saturated linkage map for alfalfa that greatly improved genome coverage relative to previous maps and that will facilitate investigation of genome structure. GBS could be used in breeding populations to accelerate molecular breeding in alfalfa. Copyright © 2014 Li et al.

  6. 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.

  7. Construction of a genetic linkage map of Thlaspi caerulescens and quantitative trait loci analysis of zinc accumulation.

    Science.gov (United States)

    Assunção, Ana G L; Pieper, Bjorn; Vromans, Jaap; Lindhout, Pim; Aarts, Mark G M; Schat, Henk

    2006-01-01

    Zinc (Zn) hyperaccumulation seems to be a constitutive species-level trait in Thlaspi caerulescens. When compared under conditions of equal Zn availability, considerable variation in the degree of hyperaccumulation is observed among accessions originating from different soil types. This variation offers an excellent opportunity for further dissection of the genetics of this trait. A T. caerulescens intraspecific cross was made between a plant from a nonmetallicolous accession [Lellingen (LE)], characterized by relatively high Zn accumulation, and a plant from a calamine accession [La Calamine (LC)], characterized by relatively low Zn accumulation. Zinc accumulation in roots and shoots segregated in the F3 population. This population was used to construct an LE/LC amplified fragment length polymorphism (AFLP)-based genetic linkage map and to map quantitative trait loci (QTL) for Zn accumulation. Two QTL were identified for root Zn accumulation, with the trait-enhancing alleles being derived from each of the parents, and explaining 21.7 and 16.6% of the phenotypic variation observed in the mapping population. Future development of more markers, based on Arabidopsis orthologous genes localized in the QTL regions, will allow fine-mapping and map-based cloning of the genes underlying the QTL.

  8. 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.

  9. Validation of de-identified record linkage to ascertain hospital admissions in a cohort study

    Directory of Open Access Journals (Sweden)

    English Dallas R

    2011-04-01

    Full Text Available Abstract Background Cohort studies can provide valuable evidence of cause and effect relationships but are subject to loss of participants over time, limiting the validity of findings. Computerised record linkage offers a passive and ongoing method of obtaining health outcomes from existing routinely collected data sources. However, the quality of record linkage is reliant upon the availability and accuracy of common identifying variables. We sought to develop and validate a method for linking a cohort study to a state-wide hospital admissions dataset with limited availability of unique identifying variables. Methods A sample of 2000 participants from a cohort study (n = 41 514 was linked to a state-wide hospitalisations dataset in Victoria, Australia using the national health insurance (Medicare number and demographic data as identifying variables. Availability of the health insurance number was limited in both datasets; therefore linkage was undertaken both with and without use of this number and agreement tested between both algorithms. Sensitivity was calculated for a sub-sample of 101 participants with a hospital admission confirmed by medical record review. Results Of the 2000 study participants, 85% were found to have a record in the hospitalisations dataset when the national health insurance number and sex were used as linkage variables and 92% when demographic details only were used. When agreement between the two methods was tested the disagreement fraction was 9%, mainly due to "false positive" links when demographic details only were used. A final algorithm that used multiple combinations of identifying variables resulted in a match proportion of 87%. Sensitivity of this final linkage was 95%. Conclusions High quality record linkage of cohort data with a hospitalisations dataset that has limited identifiers can be achieved using combinations of a national health insurance number and demographic data as identifying variables.

  10. A genome-wide linkage study of individuals with high scores on NEO personality traits.

    Science.gov (United States)

    Amin, N; Schuur, M; Gusareva, E S; Isaacs, A; Aulchenko, Y S; Kirichenko, A V; Zorkoltseva, I V; Axenovich, T I; Oostra, B A; Janssens, A C J W; van Duijn, C M

    2012-10-01

    The NEO-Five-Factor Inventory divides human personality traits into five dimensions: neuroticism, extraversion, openness, conscientiousness and agreeableness. In this study, we sought to identify regions harboring genes with large effects on the five NEO personality traits by performing genome-wide linkage analysis of individuals scoring in the extremes of these traits (>90th percentile). Affected-only linkage analysis was performed using an Illumina 6K linkage array in a family-based study, the Erasmus Rucphen Family study. We subsequently determined whether distinct, segregating haplotypes found with linkage analysis were associated with the trait of interest in the population. Finally, a dense single-nucleotide polymorphism genotyping array (Illumina 318K) was used to search for copy number variations (CNVs) in the associated regions. In the families with extreme phenotype scores, we found significant evidence of linkage for conscientiousness to 20p13 (rs1434789, log of odds (LOD)=5.86) and suggestive evidence of linkage (LOD >2.8) for neuroticism to 19q, 21q and 22q, extraversion to 1p, 1q, 9p and12q, openness to 12q and 19q, and agreeableness to 2p, 6q, 17q and 21q. Further analysis determined haplotypes in 21q22 for neuroticism (P-values = 0.009, 0.007), in 17q24 for agreeableness (marginal P-value = 0.018) and in 20p13 for conscientiousness (marginal P-values = 0.058, 0.038) segregating in families with large contributions to the LOD scores. No evidence for CNVs in any of the associated regions was found. Our findings imply that there may be genes with relatively large effects involved in personality traits, which may be identified with next-generation sequencing techniques.

  11. Construction of two genetic linkage maps in cultivated tetraploid alfalfa (Medicago sativa using microsatellite and AFLP markers

    Directory of Open Access Journals (Sweden)

    Santoni Sylvain

    2003-12-01

    Full Text Available Abstract Background Alfalfa (Medicago sativa is a major forage crop. The genetic progress is slow in this legume species because of its autotetraploidy and allogamy. The genetic structure of this species makes the construction of genetic maps difficult. To reach this objective, and to be able to detect QTLs in segregating populations, we used the available codominant microsatellite markers (SSRs, most of them identified in the model legume Medicago truncatula from EST database. A genetic map was constructed with AFLP and SSR markers using specific mapping procedures for autotetraploids. The tetrasomic inheritance was analysed in an alfalfa mapping population. Results We have demonstrated that 80% of primer pairs defined on each side of SSR motifs in M. truncatula EST database amplify with the alfalfa DNA. Using a F1 mapping population of 168 individuals produced from the cross of 2 heterozygous parental plants from Magali and Mercedes cultivars, we obtained 599 AFLP markers and 107 SSR loci. All but 3 SSR loci showed a clear tetrasomic inheritance. For most of the SSR loci, the double-reduction was not significant. For the other loci no specific genotypes were produced, so the significant double-reduction could arise from segregation distortion. For each parent, the genetic map contained 8 groups of four homologous chromosomes. The lengths of the maps were 2649 and 3045 cM, with an average distance of 7.6 and 9.0 cM between markers, for Magali and Mercedes parents, respectively. Using only the SSR markers, we built a composite map covering 709 cM. Conclusions Compared to diploid alfalfa genetic maps, our maps cover about 88–100% of the genome and are close to saturation. The inheritance of the codominant markers (SSR and the pattern of linkage repulsions between markers within each homology group are consistent with the hypothesis of a tetrasomic meiosis in alfalfa. Except for 2 out of 107 SSR markers, we found a similar order of markers on

  12. Genetic linkage analysis supports the presence of two susceptibility loci for alcoholism and heavy drinking on chromosome 1p22.1-11.2 and 1q21.3-24.2

    Directory of Open Access Journals (Sweden)

    Curtis David

    2005-03-01

    Full Text Available Abstract Background In order to confirm a previous finding of linkage to alcoholism on chromosome 1 we have carried out a genetic linkage study. Methods DNA from eighteen families, densely affected by alcoholism, was used to genotype a set of polymorphic microsatellite markers at loci approximately 10 centimorgans apart spanning the short arm and part of the long arm of chromosome 1. Linkage analyses were performed using the classical lod score and a model-free method. Three different definitions of affection status were defined, these were 1. Heavy Drinking (HD where affected subjects drank more than the Royal College of Psychiatrists recommended weekly amount. 2. The Research Diagnostic Criteria for alcoholism (RDCA 3. Alcohol Dependence Syndrome (ADS as defined by Edwards and Gross (1976 and now incorporated into ICD10 and DSMIV. Results Linkage analyses with the markers D1S1588, D1S2134, D1S1675 covering the cytogenetic region 1p22.1-11.2 all gave positive two point and multipoint lods with a maximum lod of 1.8 at D1S1588 (1p22.1 for the RDCA definition of alcoholism. Another lod of 1.8 was found with D1S1653 in the region 1q21.3-24.2 using the HD affection model. Conclusion These results both support the presence of linkage in the 1p22.1-11.2 region which was previously implicated by the USA Collaborative Study of the Genetics of Alcoholism (COGA study and also suggest the presence of another susceptibility locus at 1q21.3-24.2.

  13. Procedure di record linkage in epidemiologia: uno studio multicentrico italiano, Record-linkage procedures in epidemiology: an italian multicentre study

    OpenAIRE

    Fornai, Carla; Madotto, Fabiana; Romanelli, Anna; Pepe, Pasquale; Raciti, Mauro; Tancioni, Valeria; Chini, Francesco; Trerotoli, Paolo; Bartolomeo, Nicola; Serio, Gabriella; Cesana, Giancarlo; Corrao, Giovanni

    2008-01-01

    Abstract Objective: to compare record linkage (RL) procedures adopted in several Italian settings and a standard probabilistic RL procedure for matching data from electronic health care databases. Design: two health care archives are matched: the hospital discharges (HD) archive and the population registry of four Italian areas. Exact deterministic, stepwise deterministic techniques and a standard probabilistic RL procedure are applied to match HD for acute myocardial infarction (AMI) and dia...

  14. Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index

    DEFF Research Database (Denmark)

    Minster, Ryan L; Sanders, Jason L; Singh, Jatinder;

    2015-01-01

    BACKGROUND: The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems. METHODS: We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted...

  15. The genetic architecture of domestication in the chicken: effects of pleiotropy and linkage.

    Science.gov (United States)

    Wright, D; Rubin, C-J; Martinez Barrio, A; Schütz, K; Kerje, S; Brändström, H; Kindmark, A; Jensen, P; Andersson, L

    2010-12-01

    The extent of pleiotropy and epistasis in quantitative traits remains equivocal. In the case of pleiotropy, multiple quantitative trait loci are often taken to be pleiotropic if their confidence intervals overlap, without formal statistical tests being used to ascertain if these overlapping loci are statistically significantly pleiotropic. Additionally, the degree to which the genetic correlations between phenotypic traits are reflected in these pleiotropic quantitative trait loci is often variable, especially in the case of antagonistic pleiotropy. Similarly, the extent of epistasis in various morphological, behavioural and life-history traits is also debated, with a general problem being the sample sizes required to detect such effects. Domestication involves a large number of trade-offs, which are reflected in numerous behavioural, morphological and life-history traits which have evolved as a consequence of adaptation to selective pressures exerted by humans and captivity. The comparison between wild and domestic animals allows the genetic analysis of the traits that differ between these population types, as well as being a general model of evolution. Using a large F(2) intercross between wild and domesticated chickens, in combination with a dense SNP and microsatellite marker map, both pleiotropy and epistasis were analysed. The majority of traits were found to segregate in 11 tight 'blocks' and reflected the trade-offs associated with domestication. These blocks were shown to have a pleiotropic 'core' surrounded by more loosely linked loci. In contrast, epistatic interactions were almost entirely absent, with only six pairs identified over all traits analysed. These results give insights both into the extent of such blocks in evolution and the development of domestication itself.

  16. Genome-wide linkage analysis for human longevity

    DEFF Research Database (Denmark)

    Beekman, Marian; Blanché, Hélène; Perola, Markus

    2013-01-01

    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...

  17. Exclusion of linkage between hypokalemic periodic paralysis and a candidate region in 1q31-32 suggests genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Sillen, A.; Wadelius, C.; Gustabson, K.H. [University Hospital, Uppsala (Sweden)] [and others

    1994-09-01

    Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disease with attacks of paralysis of varying severity. The attacks occur at intervals of days to years in otherwise healthy people combined with hypokalemia during attacks. The paralysis attacks are precipitated by a number of different factors, like carbohydrate-rich meals, cold, exercise and mental stress. Recently linkage for HOKPP was shown for chromosome 1q31-32 and the disease was mapped between D1S413 and D1S249. The gene for the calcium channel alfa1-subunit (CACNL 1A3) maps to this interval and in two families no recombination was found between a polymorphism in the CACNL 1A3 gene and the disease. This gene is therefore considered to be a candidate for HOKPP. The analysis of a large Danish family excludes linkage to this region and to the CACNL 1A3 gene. In each direction from D1S413, 18.8 cM could be excluded and for D1S249, 14.9 cM. The present study clearly excludes the possibility that the gene causing HOKPP in a large Danish family is located in the region 1q31-32. This result shows that HOKPP is a heterogenous disease, with only one mapped gene so far.

  18. 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.

  19. Nature, Genetics and the Biophilia Connection: Exploring Linkages with Social Work Values and Practice

    Directory of Open Access Journals (Sweden)

    Fred H. Besthorn

    2003-05-01

    Full Text Available Social work’s notion of environment and its environmental responsibilities has always been narrowly defined. The profession has tended to either neglect natural environmental issues or accept shallow, ecological conceptualizations of nature as something other, quite separate from the human enterprise and/or outside the reach of social work activity. The Biophilia Hypothesis, first articulated by Harvard biologist E.O.Wilson in 1984, offers social work as a fundamentally different view of the person/environment construct and argues for a primary shift in the way the profession views its relationship with the natural world. This article traces the conceptual development of the Biophilic theory and reviews pivotal empirical evidence explicitly arguing for the essential Biophilic premise that humans have acquired, through their long evolutionary history, a strong genetic predisposition for nature and natural settings. It offers key insights and examples for incorporating Biophilia into social work’s values and knowledge base and how it may impact the profession’s practice strategies and techniques.

  20. Influence of genotyping error in linkage mapping for complex traits – an analytic study

    Directory of Open Access Journals (Sweden)

    van Houwelingen Hans C

    2008-08-01

    Full Text Available Abstract Background Despite the current trend towards large epidemiological studies of unrelated individuals, linkage studies in families are still thoroughly being utilized as tools for disease gene mapping. The use of the single-nucleotide-polymorphisms (SNP array technology in genotyping of family data has the potential to provide more informative linkage data. Nevertheless, SNP array data are not immune to genotyping error which, as has been suggested in the past, could dramatically affect the evidence for linkage especially in selective designs such as affected sib pair (ASP designs. The influence of genotyping error on selective designs for continuous traits has not been assessed yet. Results We use the identity-by-descent (IBD regression-based paradigm for linkage testing to analytically quantify the effect of simple genotyping error models under specific selection schemes for sibling pairs. We show, for example, that in extremely concordant (EC designs, genotyping error leads to decreased power whereas it leads to increased type I error in extremely discordant (ED designs. Perhaps surprisingly, the effect of genotyping error on inference is most severe in designs where selection is least extreme. We suggest a genomic control for genotyping errors via a simple modification of the intercept in the regression for linkage. Conclusion This study extends earlier findings: genotyping error can substantially affect type I error and power in selective designs for continuous traits. Designs involving both EC and ED sib pairs are fairly immune to genotyping error. When those designs are not feasible the simple genomic control strategy that we suggest offers the potential to deliver more robust inference, especially if genotyping is carried out by SNP array technology.

  1. 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.

  2. 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.

  3. Leather Industry Business Linkages (Case Study in District Magetan

    Directory of Open Access Journals (Sweden)

    Dilahur Dilahur

    2004-01-01

    Full Text Available Leather industry in Magetan covers two forms; they are tanning and leathercraft. During 1960 and 1970, the leather industry decreased in its production, but in 1990 Magetan becomes the center of leather industry. Its development appeals to be studied closely. The goals of this study are to know the relation between tanning and leathercraft, the connection between these industries and other economic ativities, and their connection with production factor. This study uses survey methhod. The respondents are taken proportionally from both of those leather industries. The data is obtained inetrviewing the respondents with questionnaire that related to the input and out put of the industry. The result of this study shows that there is no relationship between the kind of industries (small and household industry and its capital, especially in its raw material (44,44%. The relationship between tanning and leathercraft is low, because it is only 24,2% input of leathercraft which taken from output of tanning. The region relationship for tanning is larger, because the products that are sold to other regions are 97,22% for tanning and 68,29% for leathercraft. Its relationship to other sectors especially for labour supply is 56,48% from farming and trade sectors in marketing.

  4. Development of cleaved amplified polymorphic sequence markers and a CAPS-based genetic linkage map in watermelon (Citrullus lanatus [Thunb.] Matsum. and Nakai) constructed using whole-genome re-sequencing data.

    Science.gov (United States)

    Liu, Shi; Gao, Peng; Zhu, Qianglong; Luan, Feishi; Davis, Angela R; Wang, Xiaolu

    2016-03-01

    Cleaved amplified polymorphic sequence (CAPS) markers are useful tools for detecting single nucleotide polymorphisms (SNPs). This study detected and converted SNP sites into CAPS markers based on high-throughput re-sequencing data in watermelon, for linkage map construction and quantitative trait locus (QTL) analysis. Two inbred lines, Cream of Saskatchewan (COS) and LSW-177 had been re-sequenced and analyzed by Perl self-compiled script for CAPS marker development. 88.7% and 78.5% of the assembled sequences of the two parental materials could map to the reference watermelon genome, respectively. Comparative assembled genome data analysis provided 225,693 and 19,268 SNPs and indels between the two materials. 532 pairs of CAPS markers were designed with 16 restriction enzymes, among which 271 pairs of primers gave distinct bands of the expected length and polymorphic bands, via PCR and enzyme digestion, with a polymorphic rate of 50.94%. Using the new CAPS markers, an initial CAPS-based genetic linkage map was constructed with the F2 population, spanning 1836.51 cM with 11 linkage groups and 301 markers. 12 QTLs were detected related to fruit flesh color, length, width, shape index, and brix content. These newly CAPS markers will be a valuable resource for breeding programs and genetic studies of watermelon.

  5. Study on genetic coadaptability of wild quail populations in China

    Institute of Scientific and Technical Information of China (English)

    CHANG; Guobin; CHANG; Hong; LIU; Xiangping; YANG; Zhangping; CHEN; Guohong; ZHAO; Wenming; JI; Dejun; XUE; Yan; HUANG; Feng; HASSAN; Hussein

    2006-01-01

    Genetic coadaptability of wild Japanese quail, wild Common quail and Domestic quail populations in China was studied using 7 microsatellite DNA markers and Monte Carlo method to test genetic disequilibrium. The molecular effects of genetic coadaptability were analyzed through a new statistical model of neutral site. The results showed that genetic coadaptability dominated the genetic disequilibrium of the three quail populations, and totally 16.67%, 9.66% and 10.05% of non-allelic combinations were in the genetic disequilibrium in wild Japanese quail, wild Common quail and Domestic quail populations, respectively. Genetic coadaptability existed at almost all the tested sites. In the molecular point of view, genetic coadaptability plays an important role of keeping lots of polymorphisms in natural populations. Therefore, it is another key factor to the genetic disequilibrium in the population except for linkage. The results enrich the conceptions and connotations of genetic disequilibrium, and help us know more about genetic coadaptability and its effects, and lay a foundation of evaluation and protection of wild quail genetic resources in China.

  6. Genetic epidemiology of tuberculosis susceptibility: impact of study design.

    Science.gov (United States)

    Stein, Catherine M

    2011-01-20

    Several candidate gene studies have provided evidence for a role of host genetics in susceptibility to tuberculosis (TB). However, the results of these studies have been very inconsistent, even within a study population. Here, we review the design of these studies from a genetic epidemiological perspective, illustrating important differences in phenotype definition in both cases and controls, consideration of latent M. tuberculosis infection versus active TB disease, population genetic factors such as population substructure and linkage disequilibrium, polymorphism selection, and potential global differences in M. tuberculosis strain. These considerable differences between studies should be accounted for when examining the current literature. Recommendations are made for future studies to further clarify the host genetics of TB.

  7. A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage

    DEFF Research Database (Denmark)

    Kolte, Astrid Marie; Nielsen, H S; Moltke, Ida;

    2011-01-01

    Previously, siblings of patients with idiopathic recurrent miscarriage (IRM) have been shown to have a higher risk of miscarriage. This study comprises two parts: (i) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM an...

  8. 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.

  9. Linkage analysis in alcohol dependence.

    Science.gov (United States)

    Windemuth, C; Hahn, A; Strauch, K; Baur, M P; Wienker, T F

    1999-01-01

    Alcohol dependence often is a familial disorder and has a genetic component. Research in causative factors of alcoholism is coordinated by a multi-center program, COGA [The Collaborative Study on the Genetics of Alcoholism, Begleiter et al., 1995]. We analyzed a subset of the COGA family sample, 84 pedigrees of Caucasian ancestry comprising 745 persons, 339 of whom are affected according to DSM-III-R and Feighner criteria. Using parametric and nonparametric methods, evidence for linkage was found on chromosome 1 (near markers D1S532, D1S1588, and D1S534), as well as on chromosome 15 (near marker D15S642). Other regions of the genome showed suggestive evidence for contributing loci. Related findings are discussed in recent publications investigating linkage in humans [Reich et al., 1998] and mice [Melo et al., 1996].

  10. Suicides after pregnancy in Finland, 1987-94: register linkage study.

    OpenAIRE

    1996-01-01

    OBJECTIVE: To determine rates of suicide associated with pregnancy by the type of pregnancy. DESIGN: Register linkage study. Information on suicides in women of reproductive age was linked with the Finnish birth, abortion, and hospital discharge registers to find out how many women who committed suicide had had a completed pregnancy during her last year of life. SETTING: Nationwide data from Finland. SUBJECTS: Women who committed suicide in 1987-94. RESULTS: There were 73 suicides associated ...

  11. Historical measures of social context in life course studies: retrospective linkage of addresses to decennial censuses

    Directory of Open Access Journals (Sweden)

    Whitsel Eric A

    2004-11-01

    Full Text Available Abstract Background There is evidence of a contribution of early life socioeconomic exposures to the risk of chronic diseases in adulthood. However, extant studies investigating the impact of the neighborhood social environment on health tend to characterize only the current social environment. This in part may be due to complexities involved in obtaining and geocoding historical addresses. The Life Course Socioeconomic Status, Social Context, and Cardiovascular Disease Study collected information on childhood (1930–1950 and early adulthood (1960–1980 place of residence from 12,681 black and white middle-aged and older men and women from four U.S. communities to link participants with census-based socioeconomic indicators over the life course. Results Most (99% participants were linked to 1930–50 county level socioeconomic census data (the smallest level of aggregation universally available during this time period corresponding to childhood place of residence. Linkage did not vary by race, gender, birth cohort, or level of educational attainment. A commercial geocoding vendor processed participants' self-reported street addresses for ages 30, 40, and 50. For 1970 and 1980 censuses, spatial coordinates were overlaid onto shape files containing census tract boundaries; for 1960 no shape files existed and comparability files were used. Several methods were tested for accuracy and to increase linkage. Successful linkage to historical census tracts varied by census (66% for 1960, 76% for 1970, 85% for 1980. This compares to linkage rates of 94% for current addresses provided by participants over the course of the ARIC examinations. Conclusion There are complexities and limitations in characterizing the past social context. However, our results suggest that it is feasible to characterize the earlier social environment with known levels of measurement error and that such an approach should be considered in future studies.

  12. 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.

  13. Report from the Maryland epidemiology schizophrenia linkage study: No evidence for linkage between schizophrenia and a number of candidate and other genomic regions using a complex dominant model

    Energy Technology Data Exchange (ETDEWEB)

    Karayiorgou, M.; Hwang, J.; Elango, R. [Massachusetts Institute of Technology, Cambridge, MA (United States)] [and others

    1994-12-15

    Our collaborative group has undertaken a linkage study of schizophrenia, using a systematic sample of patients admitted to Maryland hospitals. An initial sample of 39 families, each having two or more affecteds, was available for genotyping candidate genes, candidate regions, and highly polymorphic markers randomly distributed throughout the genome. We used a single complex dominant model (with a disease gene frequency of 0.005 and age-dependent penetrance for affected phenotype: for under 35, penetrance = .45; for 35 and older, penetrance = .85). We report here 130 markers which met the exclusion criteria of LOD score < -2.00 at theta > 0.01 in at least 10 informative families, and no evidence for heterogeneity. We also report here markers that were tested as candidates for linkage to the schizophrenic phenotype. They were selected based on the following criteria: (a) proximity to reported chromosomal rearrangements (both 5q and 11q), (b) suggestions of linkage from other families (5q), or (c) presence of a candidate gene (5q, 11q, 3q: dopamine receptors 1, 2, and 3, respectively). We also tested for mutations of codon 717 in exon 17 of the amyloid precursor protein (APP) gene and were unable to detect the C to T substitution in our schizophrenic group. 48 refs., 2 tabs.

  14. Joint-linkage mapping and GWAS reveal extensive genetic loci that regulate male inflorescence size in maize

    Science.gov (United States)

    Both insufficient and excessive male inflorescence size leads to a reduction in maize yield. Knowledge of the genetic architecture of male inflorescence is essential to achieve the optimum inflorescence size for maize breeding. In this study, we used approximately eight thousand inbreds, including b...

  15. A genetic linkage map for watermelon derived from a testcross population: ( Citrullus lanatus var. citroides x C. lanatus var. lanatus) x Citrullus colocynthis.

    Science.gov (United States)

    Levi, A.; Thomas, E.; Joobeur, T.; Zhang, X.; Davis, A.

    2002-09-01

    A genetic linkage map was constructed for watermelon using a testcross population [Plant Accession Griffin 14113 ( Citrullus lanatus var. citroides) x New Hampshire Midget (NHM; C. lanatus var. lanatus)] x U.S. Plant Introduction (PI) 386015 ( Citrullus colocynthis). The map contains 141 randomly amplified polymorphic DNA (RAPD) markers produced by 78 primers, 27 inter-simple sequence repeat (ISSR) markers produced by 17 primers, and a sequence-characterized amplified region (SCAR) marker that was previously reported as linked (1.6 cM) to race-1 Fusarium wilt [incited by Fusarium oxysporum Schlechtend.:Fr. f. sp. niveum (E.F.Sm.) W.C. Synder & H.N. Hans] resistance in watermelon. The map consists of 25 linkage groups. Among them are a large linkage group that contains 22 markers covering a mapping distance of 225.6 cM and six large groups each with 10-20 markers covering a mapping distance of 68.8 to 110.8 cM. There are five additional linkage groups consisting of 3-7 markers per group, each covering a mapping distance of 36.5 to 57.2 cM. The 13 remaining linkage groups are small, each consisting of 2-11 markers covering a mapping distance of 3.5-29.9 cM. The entire map covers a total distance of 1,166.2 cM with an average distance of 8.1 cM between two markers. This map is useful for the further development of markers linked to disease resistance and watermelon fruit qualities.

  16. A genetic study of the human low-voltage electroencephalogram.

    Science.gov (United States)

    Anokhin, A; Steinlein, O; Fischer, C; Mao, Y; Vogt, P; Schalt, E; Vogel, F

    1992-01-01

    The studied phenotype, the low-voltage electroencephalogram (LVEEG), is characterized by the absence of an alpha rhythm from the resting EEG. In previous studies, evidence was found for a simple autosomal-dominant mode of inheritance of the LVEEG. Such a polymorphism in brain function can be used as a research model for the stepwise elucidation of the molecular mechanism involved in those aspects of neuronal activity that are reflected in the EEG. Linkage with the variable number of tandem repeats (VNTR) marker CMM6 (D20S19) and localization of an LVEEG (EEGV1) gene on 20q have previously been reported, and genetic heterogeneity has been demonstrated. This latter result has been corroborated by studying new marker (MS214). The phenotype of the LVEEG is described here in greater detail. Its main characteristic is the absence of rhythmic alpha activity, especially in occipital leads, whereas other wave forms such as beta or theta waves may be present. Analysis of 17 new families (some of them large), together with 60 previously described nuclear families, supports the genetic hypothesis of an autosomal-dominant mode of inheritance. Problems connected with the analysis of linkage heterogeneity, exclusion mapping, and the study of multipoint linkage are discussed. A possible explanation of the localization of LVEEG in the close vicinity of another gene influencing synchronization of the normal EEG, the gene for benign neonatal epilepsie, is given.

  17. Genetical Genomics for Evolutionary Studies

    NARCIS (Netherlands)

    Prins, J.C.P.; Smant, G.; Jansen, R.C.

    2012-01-01

    enetical genomics combines acquired high-throughput genomic data with genetic analysis. In this chapter, we discuss the application of genetical genomics for evolutionary studies, where new high-throughput molecular technologies are combined with mapping quantitative trait loci (QTL) on the genome

  18. Defining asthma in genetic studies

    NARCIS (Netherlands)

    Koppelman, GH; Postma, DS; Meijer, G.

    1999-01-01

    Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define

  19. Defining asthma in genetic studies

    NARCIS (Netherlands)

    Koppelman, GH; Postma, DS; Meijer, G.

    1999-01-01

    Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define

  20. 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.

  1. Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

    Science.gov (United States)

    Li, Xin; Hu, Jintian; Zhang, Jiao; Jin, Qian; Wang, Duen-Mei; Yu, Jun; Zhang, Qingguo; Zhang, Yong-Biao

    2014-01-01

    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.

  2. Genetic Studies of Stuttering in a Founder Population

    Science.gov (United States)

    Wittke-Thompson, Jacqueline K.; Ambrose, Nicoline; Yairi, Ehud; Roe, Cheryl; Cook, Edwin H.; Ober, Carole; Cox, Nancy J.

    2007-01-01

    Genome-wide linkage and association analyses were conducted to identify genetic determinants of stuttering in a founder population in which 48 individuals affected with stuttering are connected in a single 232-person genealogy. A novel approach was devised to account for all necessary relationships to enable multipoint linkage analysis. Regions…

  3. Optimizing linkage and retention to hypertension care in rural Kenya (LARK hypertension study): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Vedanthan, Rajesh; Kamano, Jemima H; Naanyu, Violet; Delong, Allison K; Were, Martin C; Finkelstein, Eric A; Menya, Diana; Akwanalo, Constantine O; Bloomfield, Gerald S; Binanay, Cynthia A; Velazquez, Eric J; Hogan, Joseph W; Horowitz, Carol R; Inui, Thomas S; Kimaiyo, Sylvester; Fuster, Valentin

    2014-04-27

    Hypertension is the leading global risk factor for mortality. Hypertension treatment and control rates are low worldwide, and delays in seeking care are associated with increased mortality. Thus, a critical component of hypertension management is to optimize linkage and retention to care. This study investigates whether community health workers, equipped with a tailored behavioral communication strategy and smartphone technology, can increase linkage and retention of hypertensive individuals to a hypertension care program and significantly reduce blood pressure among them. The study will be conducted in the Kosirai and Turbo Divisions of western Kenya. An initial phase of qualitative inquiry will assess facilitators and barriers of linkage and retention to care using a modified Health Belief Model as a conceptual framework. Subsequently, we will conduct a cluster randomized controlled trial with three arms: 1) usual care (community health workers with the standard level of hypertension care training); 2) community health workers with an additional tailored behavioral communication strategy; and 3) community health workers with a tailored behavioral communication strategy who are also equipped with smartphone technology. The co-primary outcome measures are: 1) linkage to hypertension care, and 2) one-year change in systolic blood pressure among hypertensive individuals. Cost-effectiveness analysis will be conducted in terms of costs per unit decrease in blood pressure and costs per disability-adjusted life year gained. This study will provide evidence regarding the effectiveness and cost-effectiveness of strategies to optimize linkage and retention to hypertension care that can be applicable to non-communicable disease management in low- and middle-income countries. This trial is registered with (NCT01844596) on 30 April 2013.

  4. 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 ...

  5. 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...

  6. Genome-Wide Linkage and Positional Association Analyses Identify Associations of Novel AFF3 and NTM Genes with Triglycerides: The GenSalt Study

    Science.gov (United States)

    Li, Changwei; Bazzano, Lydia A.L.; Rao, Dabeeru C.; Hixson, James E.; He, Jiang; Gu, Dongfeng; Gu, Charles C.; Shimmin, Lawrence C.; Jaquish, Cashell E.; Schwander, Karen; Liu, De-Pei; Huang, Jianfeng; Lu, Fanghong; Cao, Jie; Chong, Shen; Lu, Xiangfeng; Kelly, Tanika N.

    2016-01-01

    We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. The GenSalt study was conducted among 1906 participants from 633 Han Chinese families. Lipids were measured from overnight fasting blood samples using standard methods. Multipoint quantitative trait genome-wide linkage scans were performed on the high-density lipoprotein, low-density lipoprotein, and log-transformed triglyceride phenotypes. Using dense panels of single nucleotide polymorphisms (SNPs), single-marker and gene-based association analyses were conducted to follow-up on promising linkage signals. Additive associations between each SNP and lipid phenotypes were tested using mixed linear regression models. Gene-based analyses were performed by combining P-values from single-marker analyses within each gene using the truncated product method (TPM). Significant associations were assessed for replication among 777 Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). Bonferroni correction was used to adjust for multiple testing. In the GenSalt study, suggestive linkage signals were identified at 2p11.2–2q12.1 [maximum multipoint LOD score (MML) = 2.18 at 2q11.2] and 11q24.3–11q25 (MML = 2.29 at 11q25) for the log-transformed triglyceride phenotype. Follow-up analyses of these two regions revealed gene-based associations of charged multivesicular body protein 3 (CHMP3), ring finger protein 103 (RNF103), AF4/FMR2 family, member 3 (AFF3), and neurotrimin (NTM ) with triglycerides (P = 4 × 10−4, 1.00 × 10−5, 2.00 × 10−5, and 1.00 × 10−7, respectively). Both the AFF3 and NTM triglyceride associations were replicated among MESA study participants (P = 1.00 × 10−7 and 8.00 × 10−5, respectively). Furthermore, NTM explained the linkage signal on chromosome 11. In conclusion, we identified novel genes

  7. Linkage relationships among five enzyme-coding gene loci in the copepod Tigriopus californicus: a genetic confirmation of achiasmiatic meiosis.

    Science.gov (United States)

    Burton, R S; Feldman, M W; Swisher, S G

    1981-12-01

    Linkage relationships among five polymorphic enzyme-coding gene loci in the marine copepod Tigriopus californicus have been determined using electrophoretic analysis of progeny from laboratory matings. Phosphoglucose isomerase (PGI; EC 5.3.1.9) was found to be tightly linked to glutamate-pyruvate transaminase (GPT; EC 2.6..1.2), with only one recombinant observed in 364 progeny; glutamate-oxaloacetate transaminase (GOT; EC 2.6.1.1) is linked to the PGI-GPT pair, with a recombination fraction of approximately 0.20 in male double heterozygotes. Phosphoglucomutase (PGM; EC 2.7.5.1) and an esterase (EST; EC 3.1.1.1) are not linked to the PGI, GPT, GOT grouping, which has been designated linkage group I. Reciprocal crosses have revealed that no recombination occurs in female T. californicus; this observation confirms a previous report that meiosis in female Tigriopus is achiasmatic.

  8. Multicenter dizygotic twin cohort study confirms two linkage susceptibility loci for body mass index at 3q29 and 7q36 and identifies three further potential novel loci

    DEFF Research Database (Denmark)

    Kettunen, J; Perola, M; Martin, N G

    2009-01-01

    OBJECTIVE: To identify common loci and potential genetic variants affecting body mass index (BMI, kg m(-2)) in study populations originating from Europe. DESIGN: We combined genome-wide linkage scans of six cohorts from Australia, Denmark, Finland, the Netherlands, Sweden and the United Kingdom...... with an approximately 10-cM microsatellite marker map. Variance components linkage analysis was carried out with age, sex and country of origin as covariates. SUBJECTS: The GenomEUtwin consortium consists of twin cohorts from eight countries (Australia, Denmark, the Netherlands, Finland, Italy, Norway, Sweden...

  9. Construction of integrated genetic linkage maps of the tiger shrimp (Penaeus monodon) using microsatellite and AFLP markers.

    Science.gov (United States)

    You, E-M; Liu, K-F; Huang, S-W; Chen, M; Groumellec, M L; Fann, S-J; Yu, H-T

    2010-08-01

    The linkage maps of male and female tiger shrimp (P. monodon) were constructed based on 256 microsatellite and 85 amplified fragment length polymorphism (AFLP) markers. Microsatellite markers obtained from clone sequences of partial genomic libraries, tandem repeat sequences from databases and previous publications and fosmid end sequences were employed. Of 670 microsatellite and 158 AFLP markers tested for polymorphism, 341 (256 microsatellite and 85 AFLP markers) were used for genotyping with three F(1) mapping panels, each comprising two parents and more than 100 progeny. Chi-square goodness-of-fit test (chi(2)) revealed that only 19 microsatellite and 28 AFLP markers showed a highly significant segregation distortion (P every approximately 11.2 cM, with an observed genome length of 2033.4 cM. The female map consisted of 171 microsatellite and 36 AFLP markers spaced every approximately 13.8 cM, with an observed genome length of 2182 cM. Both maps shared 136 microsatellite markers, and the alignment between them indicated 38 homologous pairs of linkage groups including the linkage group representing the sex chromosome. The karyotype of P. monodon is also presented. The tentative assignment of the 44 pairs of P. monodon haploid chromosomes showed the composition of forty metacentric, one submetacentric and three acrocentric chromosomes. Our maps provided a solid foundation for gene and QTL mapping in the tiger shrimp.

  10. Construction of a Genetic Linkage Map in Mungbean%绿豆高密度分子遗传图谱的构建

    Institute of Scientific and Technical Information of China (English)

    吴传书; 王丽侠; 王素华; 陈红霖; 吴健新; 程须珍; 杨晓明

    2014-01-01

    色体上面的标记数为35-92个,平均53.18个。标记位点数最多的连锁群LG1含92个标记,长度为112.8 cM;标记位点数最少的连锁群LG11仅含有35个标记,长度为48.7 cM。对图谱的585个标记位点进行χ2测验,在P<0.05和P<0.01条件下,分别有79个和151个标记表现为偏分离,占总标记位点数的39.3%。【结论】构建了一张目前国内外发表的标记数最多、密度最高的绿豆遗传连锁图谱。%[Objective]On the basis of previous studies, a genetic map of mungbean was constructed by using genome SSR, EST-SSR, STS primers of mungbean and common bean to build a platform for positioning important traits related genes, cloning and molecular marker-assisted breeding of new varieties of mungbean.[Method]A total of 6 686 SSR, EST-SSR, STS primers of mungbean and common bean, including 6 100 genome SSR, 149 EST-SSR, 13 STS primer pairs of mungbean, and 424 genome SSR primers of common bean, were used for PCR amplification to screen polymorphic markers between Australia-imported Berken (highly susceptible cultivar)×ACC41 (highly resistant wild species) and a RIL derived from these two genotypes were tested with the polymorphic markers. Combined with the molecular marker data of previous studies, Mapmarker/Exp 3.0 software was used for map construction and set LOD≥3.0, the maximum figure at 50.00 cM. Finally, Joinmap 4.0 software was used for map integration.[Result]In this study, from the two parents, 6 686 SSR primers were screened, a total of 3 691 pairs of primers were amplified stable products, 588 pairs of polymorphic primers were obtained. Among them, mungbean SSR primers 6 100 pairs, effective amplification 3 459 pairs, the effective rate of 56.7%, obtained 559 pairs of polymorphic primers;Mungbean EST-SSR primers 149 pairs, effective amplification 126 pairs, the effective rate of 84.6%, obtained 21 pairs of polymorphic primers;Common bean SSR primers 424 pairs, effective

  11. Utilizing linkage disequilibrium information from Indian Genome Variation Database for mapping mutations: SCA12 case study

    Indian Academy of Sciences (India)

    Samira Bahl; Ikhlak Ahmed; The Indian Genome Variation Consortium; Mitali Mukerji

    2009-04-01

    Stratification in heterogeneous populations poses an enormous challenge in linkage disequilibrium (LD) based identification of causal loci using surrogate markers. In this study, we demonstrate the enormous potential of endogamous Indian populations for mapping mutations in candidate genes using minimal SNPs, mainly due to larger regions of LD. We show this by a case study of the PPP2R2B gene (∼400 kb) that harbours a CAG repeat, expansion of which has been implicated in spinocerebellar ataxia type 12 (SCA12). Using LD information derived from Indian Genome Variation database (IGVdb) on populations which share similar ethnic and linguistic backgrounds as the SCA12 study population, we could map the causal loci using a minimal set of three SNPs, without the generation of additional basal data from the ethnically matched population. We could also demonstrate transferability of tagSNPs from a related HapMap population for mapping the mutation.

  12. Epidemiology Data from the Scottish Health and Ethnicity Linkage Study (SHELS

    Directory of Open Access Journals (Sweden)

    Judith Fernandez

    2014-11-01

    Full Text Available We linked the 2001 Scottish Census, which contains ethnicity, socio-economic and demographic data to health and death records, creating an anonymised retrospective cohort study of 4.65 million people to assess the association between ethnicity and health outcomes in Scotland. The databases contain data mostly from hospital discharge and mortality records, but also from other registers.  The databases are stored in a safe haven at the National Records of Scotland (NRS. NRS is currently exploring the feasibility of making Scottish Health and Ethnicity Linkage Study (SHELS data open access while ensuring that the same level of confidentiality is maintained. If SHELS becomes open access it could be reused, with the appropriate approvals, to assess the influence of other socio-economic or demographic measures on the Scottish population’s health.

  13. 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.

  14. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

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

    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 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...

  15. A genetic linkage map of Phaseolus vulgaris L. and localization of genes for specific resistance to six races of anthracnose (Colletotrichum lindemuthianum).

    Science.gov (United States)

    Rodríguez-Suárez, Cristina; Méndez-Vigo, Belén; Pañeda, Astrid; Ferreira, Juan José; Giraldez, Ramón

    2007-02-01

    A genetic map of common bean was constructed using 197 markers including 152 RAPDs, 32 RFLPs, 12 SCARs, and 1 morphological marker. The map was established by using a F(2) population of 85 individuals from the cross between a line derived from the Spanish landrace Andecha (Andean origin) and the Mesoamerican genotype A252. The resulting map covers about 1,401.9 cM, with an average marker distance of 7.1 cM and includes molecular markers linked to disease resistance genes for anthracnose, bean common mosaic virus, bean golden yellow mosaic virus, common bacterial blight, and rust. Resistance to races 6, 31, 38, 39, 65, and 357 of the pathogenic fungus Colletotrichum lindemuthianum (anthracnose) was evaluated in F(3) families derived from the corresponding F(2) individuals. The intermediate resistance to race 65 proceeding from Andecha can be explained by a single dominant gene located on linkage group B1, corresponding to the Co-1 gene. The recombination between the resistance specificities proceeding from A252 agrees with the assumption that total resistance to races 6, 31, 38, 39, 65, and 357, is organized in two clusters. One cluster, located on B4 linkage group, includes individual genes for specific resistance to races 6, 38, 39, and 357. The second cluster is located on linkage group B11 and includes individual genes for specific resistance to races 6, 31, 38, 39, and 65. These two clusters correspond to genes Co-3/Co-9 and Co-2, respectively. It is concluded that most anthracnose resistance Co- genes, previously described as single major genes conferring resistance to several races, could be organized as clusters of different genes conferring race-specific resistance.

  16. Probabilistic data linkage: a case study of comparative effectiveness in COPD

    Directory of Open Access Journals (Sweden)

    Christopher M Blanchette

    2013-10-01

    Full Text Available Background: In this era of comparative effectiveness research, new, advanced techniques are being investigated by the research community to overcome the limitations of existing data sources. We describe the approach of probabilistic data linkage as a means to address this critical issue. Methods: We employed a historical retrospective cohort design. Patients aged 40 and older with a principal or secondary diagnosis of COPD (ICD-9-CM codes 491.xx, 492.xx, and 496 and at least 3 years of continuous enrollment between January 1, 2004 and April 30, 2009 were selected from two US-based commercial administrative claims databases. The index date was designated as the date of the first claim (defined by a 12-month wash-out pre-index period for the study drugs, for illustration purposes referred to as Treatment 1 or Treatment 2. The primary effectiveness measure was risk of any COPD-related exacerbation observed in the 12-month post-index period, with baseline characteristics being identified in the 12-month pre-index period. Results: The percentage of the study sample receiving Treatment 1 at index who had an exacerbation was 39.3% for Database A and 39.7% for Database B; for Treatment 2, the percentages were 46.3% and 47.1%, respectively. The event rate of hospitalizations in each database sample was nearly identical as were the odds ratio and corresponding confidence intervals from the adjusted logistic regression models (OR – Database A: 0.72, Database B: 0.74, Database A with imputed outcomes: 0.72. Conclusions: The probabilistic linkage demonstrated that patients from different databases matched on similar pre-index characteristics may demonstrate similar outcomes in the post-index period.

  17. Linkage disequilibrium and demographic history of the isolated population of the Faroe Islands

    DEFF Research Database (Denmark)

    Jorgensen, Tove H; Degn, Birte; Wang, August G;

    2002-01-01

    The isolated population of the Faroe Islands has a history of recent expansion after being limited to a small size for centuries. Such an isolated population may be ideal for linkage disequilibrium mapping of disease genes if linkage disequilibrium (LD) extends over large regions. Analyses of 18 ...... by random genetic drift. The implications for future gene mapping studies are discussed....

  18. Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder

    NARCIS (Netherlands)

    Zhou, Kaixin; Dempfle, Astrid; Arcos-Burgos, Mauricio; Bakker, Steven C; Banaschewski, Tobias; Biederman, Joseph; Buitelaar, Jan; Castellanos, F Xavier; Doyle, Alysa; Ebstein, Richard P; Ekholm, Jenny; Forabosco, Paola; Franke, Barbara; Freitag, Christine; Friedel, Susann; Gill, Michael; Hebebrand, Johannes; Hinney, Anke; Jacob, Christian; Lesch, Klaus Peter; Loo, Sandra K; Lopera, Francisco; McCracken, James T; McGough, James J; Meyer, Jobst; Mick, Eric; Miranda, Ana; Muenke, Maximilian; Mulas, Fernando; Nelson, Stanley F; Nguyen, T Trang; Oades, Robert D; Ogdie, Matthew N; Palacio, Juan David; Pineda, David; Reif, Andreas; Renner, Tobias J; Roeyers, Herbert; Romanos, Marcel; Rothenberger, Aribert; Schäfer, Helmut; Sergeant, Joseph; Sinke, Richard J; Smalley, Susan L; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; van der Meulen, Emma; Walitza, Susanne; Warnke, Andreas; Lewis, Cathryn M; Faraone, Stephen V; Asherson, Philip

    2008-01-01

    Genetic contribution to the development of attention deficit hyperactivity disorder (ADHD) is well established. Seven independent genome-wide linkage scans have been performed to map loci that increase the risk for ADHD. Although significant linkage signals were identified in some of the studies, th

  19. 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.

  20. A new genetic linkage map of tomato based on a Solanum lycopersicum x S. pimpinellifolium RIL population displaying locations of candidate pathogen response genes.

    Science.gov (United States)

    Ashrafi, Hamid; Kinkade, Matthew; Foolad, Majid R

    2009-11-01

    The narrow genetic base of the cultivated tomato, Solanum lycopersicum L., necessitates introgression of new variation from related species. Wild tomato species represent a rich source of useful genes and traits. Exploitation of genetic variation within wild species can be facilitated by the use of molecular markers and genetic maps. Recently we identified an accession (LA2093) within the red-fruited wild tomato species Solanum pimpinellifolium L. with exceptionally desirable characteristics, including disease resistance, abiotic stress tolerance, and high fruit lycopene content. To facilitate genetic characterization of such traits and their exploitation in tomato crop improvement, we developed a new recombinant inbred line (RIL) population from a cross between LA2093 and an advanced tomato breeding line (NCEBR-1). Furthermore, we constructed a medium-density molecular linkage map of this population using 294 polymorphic markers, including standard RFLPs, EST sequences (used as RFLP probes), CAPS, and SSRs. The map spanned 1091 cM of the tomato genome with an average marker spacing of 3.7 cM. A majority of the EST sequences, which were mainly chosen based on the putative role of their unigenes in disease resistance, defense-related response, or fruit quality, were mapped onto the tomato chromosomes for the first time. Co-localizations of relevant EST sequences with known disease resistance genes in tomato were also examined. This map will facilitate identification, genetic exploitation, and positional cloning of important genes or quantitative trait loci in LA2093. It also will allow the elucidation of the molecular mechanism(s) underlying important traits segregating in the RIL population. The map may further facilitate characterization and exploitation of genetic variation in other S. pimpinellifolium accessions as well as in modern cultivars of tomato.

  1. Genetic linkage analysis of the lesser grain borer Rhyzopertha dominica identifies two loci that confer high-level resistance to the fumigant phosphine.

    Science.gov (United States)

    Schlipalius, David I; Cheng, Qiang; Reilly, Paul E B; Collins, Patrick J; Ebert, Paul R

    2002-01-01

    High levels of inheritable resistance to phosphine in Rhyzopertha dominica have recently been detected in Australia and in an effort to isolate the genes responsible for resistance we have used random amplified DNA fingerprinting (RAF) to produce a genetic linkage map of R. dominica. The map consists of 94 dominant DNA markers with an average distance between markers of 4.6 cM and defines nine linkage groups with a total recombination distance of 390.1 cM. We have identified two loci that are responsible for high-level resistance. One provides approximately 50x resistance to phosphine while the other provides 12.5x resistance and in combination, the two genes act synergistically to provide a resistance level 250x greater than that of fully susceptible beetles. The haploid genome size has been determined to be 4.76 x 10(8) bp, resulting in an average physical distance of 1.2 Mbp per map unit. No recombination has been observed between either of the two resistance loci and their adjacent DNA markers in a population of 44 fully resistant F5 individuals, which indicates that the genes are likely to reside within 0.91 cM (1.1 Mbp) of the DNA markers. PMID:12072472

  2. Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease

    NARCIS (Netherlands)

    Khor, Chiea Chuen; Davila, Sonia; Shimizu, Chisato; Sheng, Stephanie; Matsubara, Tomoyo; Suzuki, Yasuo; Newburger, Jane W.; Baker, Annette; Burgner, David; Breunis, Willemijn; Kuijpers, Taco; Wright, Victoria J.; Levin, Michael; Hibberd, Martin L.; Burns, Jane C.

    Background Kawasaki disease (KD) is a self limited vasculitis in which host genetics plays a prominent role. To further the understanding of the role of host genetics in KD, a three-stage genetic study was conducted that began with a family linkage study and ultimately involved more than 3000

  3. Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease

    NARCIS (Netherlands)

    Khor, C.C.; Davila, S.; Shimizu, C.; Sheng, S.; Matsubara, T.; Suzuki, Y.; Newburger, J.W.; Baker, A.; Burgner, D.; Breunis, W.; Kuijpers, T.; Wright, V.J.; Levin, M.; Hibberd, M.L.; Burns, J.C.

    2011-01-01

    Kawasaki disease (KD) is a self limited vasculitis in which host genetics plays a prominent role. To further the understanding of the role of host genetics in KD, a three-stage genetic study was conducted that began with a family linkage study and ultimately involved more than 3000 individuals to

  4. Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease

    NARCIS (Netherlands)

    Khor, C.C.; Davila, S.; Shimizu, C.; Sheng, S.; Matsubara, T.; Suzuki, Y.; Newburger, J.W.; Baker, A.; Burgner, D.; Breunis, W.; Kuijpers, T.; Wright, V.J.; Levin, M.; Hibberd, M.L.; Burns, J.C.

    2011-01-01

    Kawasaki disease (KD) is a self limited vasculitis in which host genetics plays a prominent role. To further the understanding of the role of host genetics in KD, a three-stage genetic study was conducted that began with a family linkage study and ultimately involved more than 3000 individuals to id

  5. Genome-wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease

    NARCIS (Netherlands)

    Khor, Chiea Chuen; Davila, Sonia; Shimizu, Chisato; Sheng, Stephanie; Matsubara, Tomoyo; Suzuki, Yasuo; Newburger, Jane W.; Baker, Annette; Burgner, David; Breunis, Willemijn; Kuijpers, Taco; Wright, Victoria J.; Levin, Michael; Hibberd, Martin L.; Burns, Jane C.

    2011-01-01

    Background Kawasaki disease (KD) is a self limited vasculitis in which host genetics plays a prominent role. To further the understanding of the role of host genetics in KD, a three-stage genetic study was conducted that began with a family linkage study and ultimately involved more than 3000 indivi

  6. A complete genetic linkage map and QTL analyses for bast fibre quality traits, yield and yield components in jute (Corchorus olitorius L.).

    Science.gov (United States)

    Topdar, N; Kundu, A; Sinha, M K; Sarkar, D; Das, M; Banerjee, S; Kar, C S; Satya, P; Balyan, H S; Mahapatra, B S; Gupta, P K

    2013-01-01

    We report the first complete microsatellite genetic map of jute (Corchorus olitorius L.; 2n = 2x = 14) using an F6 recombinant inbred population. Of the 403 microsatellite markers screened, 82 were mapped on the seven linkage groups (LGs) that covered a total genetic distance of 799.9 cM, with an average marker interval of 10.7 cM. LG5 had the longest and LG7 the shortest genetic lengths, whereas LG1 had the maximum and LG7 the minimum number of markers. Segregation distortion of microsatellite loci was high (61%), with the majority of them (76%) skewed towards the female parent. Genomewide non-parametric single-marker analysis in combination with multiple quantitative trait loci (QTL)-models (MQM) mapping detected 26 definitive QTLs for bast fibre quality, yield and yield-related traits. These were unevenly distributed on six LGs, as colocalized clusters, at genomic sectors marked by 15 microsatellite loci. LG1 was the QTL-richest map sector, with the densest colocalized clusters of QTLs governing fibre yield, yield-related traits and tensile strength. Expectedly, favorable QTLs were derived from the desirable parents, except for nearly all of those of fibre fineness, which might be due to the creation of new gene combinations. Our results will be a good starting point for further genome analyses in jute.

  7. 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.

  8. Study of genetic diversity in finger millet (Eleusine coracana L ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-07-19

    Jul 19, 2010 ... portions of genome, and detects evolutionary homologous changes. ... using these data either to estimate genetic variation present within and ... Development costs ..... possibility of linkage with an area of specific phenotype. Presence of .... Assessment of genome origins and genetic diversity in the genus.

  9. Genetic characterization and linkage disequilibrium mapping of resistance to gray leaf spot in maize(Zea mays L.)

    Institute of Scientific and Technical Information of China (English)

    Liyu; Shi; Xiangling; Lv; Jianfeng; Weng; Hanyong; Zhu; Changlin; Liu; Zhuanfang; Hao; Yu; Zhou; Degui; Zhang; Mingshun; Li; Xiaoke; Ci; Xinhai; Li; Shihuang; Zhang

    2014-01-01

    Gray leaf spot(GLS),caused by Cercospora zeae-maydis,is an important foliar disease of maize(Zea mays L.)worldwide,resistance to which is controlled by multiple quantitative trait loci(QTL).To gain insights into the genetic architecture underlying the resistance to this disease,an association mapping population consisting of 161 inbred lines was evaluated for resistance to GLS in a plant pathology nursery at Shenyang in 2010 and 2011.Subsequently,a genome-wide association study,using 41,101 single-nucleotide polymorphisms(SNPs),identified 51 SNPs significantly(P<0.001)associated with GLS resistance,which could be converted into 31 QTL.In addition,three candidate genes related to plant defense were identified,including nucleotidebinding-site/leucine-rich repeat,receptor-like kinase genes similar to those involved in basal defense.Two genic SNPs,PZE-103142893 and PZE-109119001,associated with GLS resistance in chromosome bins 3.07 and 9.07,can be used for marker-assisted selection(MAS)of GLS resistance.These results provide an important resource for developing molecular markers closely linked with the target trait,enhancing breeding efficiency.

  10. Genetic Analysis and Linkage Mapping in a Resource Pig Population Using Microsatellite Markers%微卫星标记对资源猪群的遗传分析和连锁图谱构建

    Institute of Scientific and Technical Information of China (English)

    张敬虎; 熊远著; 左波; 雷明刚; 蒋思文; 李凤娥; 郑嵘; 李家连

    2007-01-01

    The use of markers and linkage map construction are important for QTL mapping in pigs.In this article, the genetic characteristics were studied and the linkage map was constructed in a pig resource population including 214 individuals by typing 39 microsatellite marker loci on Sus scrofa chromosomes, SSC4, SSC6, SSC7, SSC8, and SSC13.Results indicated that the average allele number, the average observed heterozygosity (Ho), and the average polymorphism information content (PIC) in F1 and F2population were 3.2, 0.528, 0.463 and 3.2, 0.496, 0.447, respectively.In the pig resource population, the average informative meiosis (IM) was 217.4 (44-316), and the average linkage map length between the two sexes on the five chromosomes were 172.3 cM (SSC4), 168.7 cM (SSC6), 191.7 cM (SSC7), 197.3 cM (SSC8), and 178.3 cM (SSC13).The orders of microsatellite marker loci in the linkage maps were identical to, but the length was greater than, those of USDA-MARC reference map.The results of this research showed the genetic relationship and genetic characteristics of the microsatellite markers in the pig resource family population,and the linkage map could be used to for QTL mapping in the subsequent study.%在猪数量性状位点的定位研究中,标记的使用和图谱的构建是很重要的.本研究从猪的第4、6、7、8和13染色体上选取39个微卫星标记,在来源于约克夏和梅山214头猪组成的资源群中,分析了遗传特征并构建了图谱.研究表明,平均等位基因数、平均观察杂合度(Ho)和平均多态信息含量(PIC)在F1和F2代中分别为:3.2,0.528,0.463和3.2,0.496,0.447.结果表明大多数微卫星标记位点表现为中高度杂合性.在资源群体中,平均有信息减数分裂数是217.4(44-316),而各染色体上两性平均图谱的长度分别是:172.3 cM(SSC4),168.7 cM(SSC6),191.7 cM(SSC7),197.3 cM(SSC8),178.3 cM(SSC13).与USDA-MARC的参考图谱相比,标记位点的顺序相同,但长度均较

  11. A longitudinal study of childhood social behaviour : Inter-informant agreement, inter-context agreement, and social preference linkages

    NARCIS (Netherlands)

    Kuppens, Sofie; Grietens, Hans; Onghena, Patrick; Michiels, Daisy

    2009-01-01

    This study examined inter-informant agreement, inter-context agreement, and social preference linkages for social behaviour subtypes. On two occasions, data was collected on 600 children (8-10 years old) via mother, father, teacher, and peer reports. Informant reports converged within each context a

  12. Development and Integration of Genome-Wide Polymorphic Microsatellite Markers onto a Reference Linkage Map for Constructing a High-Density Genetic Map of Chickpea.

    Science.gov (United States)

    Khajuria, Yash Paul; Saxena, Maneesha S; Gaur, Rashmi; Chattopadhyay, Debasis; Jain, Mukesh; Parida, Swarup K; Bhatia, Sabhyata

    2015-01-01

    The identification of informative in silico polymorphic genomic and genic microsatellite markers by comparing the genome and transcriptome sequences of crop genotypes is a rapid, cost-effective and non-laborious approach for large-scale marker validation and genotyping applications, including construction of high-density genetic maps. We designed 1494 markers, including 1016 genomic and 478 transcript-derived microsatellite markers showing in-silico fragment length polymorphism between two parental genotypes (Cicer arietinum ICC4958 and C. reticulatum PI489777) of an inter-specific reference mapping population. High amplification efficiency (87%), experimental validation success rate (81%) and polymorphic potential (55%) of these microsatellite markers suggest their effective use in various applications of chickpea genetics and breeding. Intra-specific polymorphic potential (48%) detected by microsatellite markers in 22 desi and kabuli chickpea genotypes was lower than inter-specific polymorphic potential (59%). An advanced, high-density, integrated and inter-specific chickpea genetic map (ICC4958 x PI489777) having 1697 map positions spanning 1061.16 cM with an average inter-marker distance of 0.625 cM was constructed by assigning 634 novel informative transcript-derived and genomic microsatellite markers on eight linkage groups (LGs) of our prior documented, 1063 marker-based genetic map. The constructed genome map identified 88, including four major (7-23 cM) longest high-resolution genomic regions on LGs 3, 5 and 8, where the maximum number of novel genomic and genic microsatellite markers were specifically clustered within 1 cM genetic distance. It was for the first time in chickpea that in silico FLP analysis at genome-wide level was carried out and such a large number of microsatellite markers were identified, experimentally validated and further used in genetic mapping. To best of our knowledge, in the presently constructed genetic map, we mapped highest

  13. Development and Integration of Genome-Wide Polymorphic Microsatellite Markers onto a Reference Linkage Map for Constructing a High-Density Genetic Map of Chickpea.

    Directory of Open Access Journals (Sweden)

    Yash Paul Khajuria

    Full Text Available The identification of informative in silico polymorphic genomic and genic microsatellite markers by comparing the genome and transcriptome sequences of crop genotypes is a rapid, cost-effective and non-laborious approach for large-scale marker validation and genotyping applications, including construction of high-density genetic maps. We designed 1494 markers, including 1016 genomic and 478 transcript-derived microsatellite markers showing in-silico fragment length polymorphism between two parental genotypes (Cicer arietinum ICC4958 and C. reticulatum PI489777 of an inter-specific reference mapping population. High amplification efficiency (87%, experimental validation success rate (81% and polymorphic potential (55% of these microsatellite markers suggest their effective use in various applications of chickpea genetics and breeding. Intra-specific polymorphic potential (48% detected by microsatellite markers in 22 desi and kabuli chickpea genotypes was lower than inter-specific polymorphic potential (59%. An advanced, high-density, integrated and inter-specific chickpea genetic map (ICC4958 x PI489777 having 1697 map positions spanning 1061.16 cM with an average inter-marker distance of 0.625 cM was constructed by assigning 634 novel informative transcript-derived and genomic microsatellite markers on eight linkage groups (LGs of our prior documented, 1063 marker-based genetic map. The constructed genome map identified 88, including four major (7-23 cM longest high-resolution genomic regions on LGs 3, 5 and 8, where the maximum number of novel genomic and genic microsatellite markers were specifically clustered within 1 cM genetic distance. It was for the first time in chickpea that in silico FLP analysis at genome-wide level was carried out and such a large number of microsatellite markers were identified, experimentally validated and further used in genetic mapping. To best of our knowledge, in the presently constructed genetic map, we mapped

  14. Development and Integration of Genome-Wide Polymorphic Microsatellite Markers onto a Reference Linkage Map for Constructing a High-Density Genetic Map of Chickpea

    Science.gov (United States)

    Gaur, Rashmi; Chattopadhyay, Debasis; Jain, Mukesh; Parida, Swarup K.; Bhatia, Sabhyata

    2015-01-01

    The identification of informative in silico polymorphic genomic and genic microsatellite markers by comparing the genome and transcriptome sequences of crop genotypes is a rapid, cost-effective and non-laborious approach for large-scale marker validation and genotyping applications, including construction of high-density genetic maps. We designed 1494 markers, including 1016 genomic and 478 transcript-derived microsatellite markers showing in-silico fragment length polymorphism between two parental genotypes (Cicer arietinum ICC4958 and C. reticulatum PI489777) of an inter-specific reference mapping population. High amplification efficiency (87%), experimental validation success rate (81%) and polymorphic potential (55%) of these microsatellite markers suggest their effective use in various applications of chickpea genetics and breeding. Intra-specific polymorphic potential (48%) detected by microsatellite markers in 22 desi and kabuli chickpea genotypes was lower than inter-specific polymorphic potential (59%). An advanced, high-density, integrated and inter-specific chickpea genetic map (ICC4958 x PI489777) having 1697 map positions spanning 1061.16 cM with an average inter-marker distance of 0.625 cM was constructed by assigning 634 novel informative transcript-derived and genomic microsatellite markers on eight linkage groups (LGs) of our prior documented, 1063 marker-based genetic map. The constructed genome map identified 88, including four major (7–23 cM) longest high-resolution genomic regions on LGs 3, 5 and 8, where the maximum number of novel genomic and genic microsatellite markers were specifically clustered within 1 cM genetic distance. It was for the first time in chickpea that in silico FLP analysis at genome-wide level was carried out and such a large number of microsatellite markers were identified, experimentally validated and further used in genetic mapping. To best of our knowledge, in the presently constructed genetic map, we mapped highest

  15. Genome wide linkage study, using a 250K SNP map, of Plasmodium falciparum infection and mild malaria attack in a Senegalese population.

    Directory of Open Access Journals (Sweden)

    Jacqueline Milet

    Full Text Available Multiple factors are involved in the variability of host's response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic factors remains unclear. Discordant results exist, even concerning the best-known malaria resistance genes that determine the structure or function of red blood cells. Here we report on a genome-wide linkage and association study for P. falciparum infection intensity and mild malaria attack among a Senegalese population of children and young adults from 2 to 18 years old. A high density single nucleotide polymorphisms (SNP genome scan (Affimetrix GeneChip Human Mapping 250K-nsp was performed for 626 individuals: i.e. 249 parents and 377 children out of the 504 ones included in the follow-up. The population belongs to a unique ethnic group and was closely followed-up during 3 years. Genome-wide linkage analyses were performed on four clinical and parasitological phenotypes and association analyses using the family based association tests (FBAT method were carried out in regions previously linked to malaria phenotypes in literature and in the regions for which we identified a linkage peak. Analyses revealed three strongly suggestive evidences for linkage: between mild malaria attack and both the 6p25.1 and the 12q22 regions (empirical p-value=5x10(-5 and 9x10(-5 respectively, and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value=1.5x10(-4. Family based association analysis pointed out one significant association between the intensity of plasmodial infection and a polymorphism located in ARHGAP26 gene in the 5q31-q33 region (p-value=3.7x10(-5. This study identified three candidate regions, two of them containing genes that could point out new pathways implicated in the response to malaria infection

  16. Genetic studies of Crohn's disease: past, present and future.

    Science.gov (United States)

    Liu, Jimmy Z; Anderson, Carl A

    2014-06-01

    The exact aetiology of Crohn's disease is unknown, though it is clear from early epidemiological studies that a combination of genetic and environmental risk factors contributes to an individual's disease susceptibility. Here, we review the history of gene-mapping studies of Crohn's disease, from the linkage-based studies that first implicated the NOD2 locus, through to modern-day genome-wide association studies that have discovered over 140 loci associated with Crohn's disease and yielded novel insights into the biological pathways underlying pathogenesis. We describe on-going and future gene-mapping studies that utilise next generation sequencing technology to pinpoint causal variants and identify rare genetic variation underlying Crohn's disease risk. We comment on the utility of genetic markers for predicting an individual's disease risk and discuss their potential for identifying novel drug targets and influencing disease management. Finally, we describe how these studies have shaped and continue to shape our understanding of the genetic architecture of Crohn's disease.

  17. Genetic diversity and bottleneck studies in the Marwari horse breed

    Indian Academy of Sciences (India)

    A. K. Gupta; M. Chauhan; S. N. Tandon; Sonia

    2005-12-01

    Genetic diversity within the Marwari breed of horses was evaluated using 26 different microsatellite pairs with 48 DNA samples from unrelated horses. This molecular characterisation was undertaken to evaluate the problem of genetic bottlenecks also, if any, in this breed. The estimated mean (± s.e.) allelic diversity was 5.9 (± 2.24), with a total of 133 alleles. A high level of genetic variability within this breed was observed in terms of high values of mean (± s.e.) effective number of alleles (3.3 ± 1.27), observed heterozygosity (0.5306 ± 0.22), expected Levene’s heterozygosity (0.6612 ± 0.15), expected Nei’s heterozygosity (0.6535 ± 0.14), and polymorphism information content (0.6120 ± 0.03). Low values of Wright’s fixation index, $F_{\\text{IS}}$ (0.2433 ± 0.05) indicated low levels of inbreeding. This basic study indicated the existence of substantial genetic diversity in the Marwari horse population. No significant genotypic linkage disequilibrium was detected across the population, suggesting no evidence of linkage between loci. A normal ‘L’ shaped distribution of mode–shift test, non-significant heterozygote excess on the basis of different models, as revealed from Sign, Standardized differences and Wilcoxon sign rank tests as well as non-significant ratio value suggested that there was no recent bottleneck in the existing Marwari breed population, which is important information for equine breeders. This study also revealed that the Marwari breed can be differentiated from some other exotic breeds of horses on the basis of three microsatellite primers.

  18. 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.

  19. Gene linkage in man and chinese hamster studied in somatic cell hybrids

    NARCIS (Netherlands)

    Westerveld, A.

    1971-01-01

    Genetic studies of higher organisms, including man, are based on the analysis of segregation and recombination events resulting from reproduction. In 1962 Pontecorvo predicted, however, that cultured cells could also be employed for this purpose. He suggested that "events, detected in certain fungi,

  20. Structure, evolution, and comparative genomics of tetraploid cotton based on a high-density genetic linkage map.

    Science.gov (United States)

    Li, Ximei; Jin, Xin; Wang, Hantao; Zhang, Xianlong; Lin, Zhongxu

    2016-06-01

    A high-density linkage map was constructed using 1,885 newly obtained loci and 3,747 previously published loci, which included 5,152 loci with 4696.03 cM in total length and 0.91 cM in mean distance. Homology analysis in the cotton genome further confirmed the 13 expected homologous chromosome pairs and revealed an obvious inversion on Chr10 or Chr20 and repeated inversions on Chr07 or Chr16. In addition, two reciprocal translocations between Chr02 and Chr03 and between Chr04 and Chr05 were confirmed. Comparative genomics between the tetraploid cotton and the diploid cottons showed that no major structural changes exist between DT and D chromosomes but rather between AT and A chromosomes. Blast analysis between the tetraploid cotton genome and the mixed genome of two diploid cottons showed that most AD chromosomes, regardless of whether it is from the AT or DT genome, preferentially matched with the corresponding homologous chromosome in the diploid A genome, and then the corresponding homologous chromosome in the diploid D genome, indicating that the diploid D genome underwent converted evolution by the diploid A genome to form the DT genome during polyploidization. In addition, the results reflected that a series of chromosomal translocations occurred among Chr01/Chr15, Chr02/Chr14, Chr03/Chr17, Chr04/Chr22, and Chr05/Chr19.

  1. Microsatellites for the genus Cucurbita and an SSR-based genetic linkage map of Cucurbita pepo L.

    Science.gov (United States)

    Gong, L; Stift, G; Kofler, R; Pachner, M; Lelley, T

    2008-06-01

    Until recently, only a few microsatellites have been available for Cucurbita, thus their development is highly desirable. The Austrian oil-pumpkin variety Gleisdorfer Olkürbis (C. pepo subsp. pepo) and the C. moschata cultivar Soler (Puerto Rico) were used for SSR development. SSR-enriched partial genomic libraries were established and 2,400 clones were sequenced. Of these 1,058 (44%) contained an SSR at least four repeats long. Primers were designed for 532 SSRs; 500 primer pairs produced fragments of expected size. Of these, 405 (81%) amplified polymorphic fragments in a set of 12 genotypes: three C. moschata, one C. ecuadorensis, and eight C. pepo representing all eight cultivar groups. On an average, C. pepo and C. moschata produced 3.3 alleles per primer pair, showing high inter-species transferability. There were 187 SSR markers detecting polymorphism between the USA oil-pumpkin variety "Lady Godiva" (O5) and the Italian crookneck variety "Bianco Friulano" (CN), which are the parents of our previous F(2) mapping population. It has been used to construct the first published C. pepo map, containing mainly RAPD and AFLP markers. Now the updated map comprises 178 SSRs, 244 AFLPs, 230 RAPDs, five SCARs, and two morphological traits (h and B). It contains 20 linkage groups with a map density of 2.9 cM. The observed genome coverage (Co) is 86.8%.

  2. Dielectric studies on mobility of the glycosidic linkage in seven disaccharides.

    Science.gov (United States)

    Kaminski, K; Kaminska, E; Wlodarczyk, P; Pawlus, S; Kimla, D; Kasprzycka, A; Paluch, M; Ziolo, J; Szeja, W; Ngai, K L

    2008-10-09

    Isobaric dielectric relaxation measurements were performed on seven chosen disaccharides. For five of them, i.e., sucrose, maltose, trehalose, lactulose, and leucrose, we were able to observe the temperature evolution of the structural relaxation process. In the case of the other disaccharides studied (lactose and cellobiose), it was impossible to obtain such information because of the large contribution of the dc conductivity and polarization of the capacitor plates to the imaginary and real part of the complex permittivity, respectively. On the other hand, in the glassy state, two secondary relaxations have been identified in the dielectric spectra of all investigated carbohydrates. The faster one (gamma) is a common characteristic feature of the entire sugar family (mono-, di-, oligo-, and polysaccharide). The molecular origin of this process is still not unambiguously identified but is expected to involve intramolecular degrees of freedom as inferred from insensitivity of its relaxation time to pressure found in some monosaccharides (fructose and ribose). The slower one (labeled beta) was recently identified to be intermolecular in origin (i.e., a Johari-Goldstein (JG) beta-relaxation), involving twisting motion of the monosugar rings around the glycosidic bond. The activation energies and dielectric strengths for the beta-relaxation determined herein provide us valuable information about the flexibility of the glycosidic bond and the mobility of this particular linkage in the disaccharides studied. In turn, this information is essential for the control of the diffusivity of drugs or water entrapped in the sugar matrix.

  3. Month of Conception and Learning Disabilities: A Record-Linkage Study of 801,592 Children.

    Science.gov (United States)

    Mackay, Daniel F; Smith, Gordon C S; Cooper, Sally-Ann; Wood, Rachael; King, Albert; Clark, David N; Pell, Jill P

    2016-10-01

    Learning disabilities have profound, long-lasting health sequelae. Affected children born over the course of 1 year in the United States of America generated an estimated lifetime cost of $51.2 billion. Results from some studies have suggested that autistic spectrum disorder may vary by season of birth, but there have been few studies in which investigators examined whether this is also true of other causes of learning disabilities. We undertook Scotland-wide record linkage of education (annual pupil census) and maternity (Scottish Morbidity Record 02) databases for 801,592 singleton children attending Scottish schools in 2006-2011. We modeled monthly rates using principal sine and cosine transformations of the month number and demonstrated cyclicity in the percentage of children with special educational needs. Rates were highest among children conceived in the first quarter of the year (January-March) and lowest among those conceived in the third (July-September) (8.9% vs 7.6%; P disabilities, and learning difficulties (e.g., dyslexia) and were absent for sensory or motor/physical impairments and mental, physical, or communication problems. Seasonality accounted for 11.4% (95% confidence interval: 9.0, 13.7) of all cases. Some biologically plausible causes of this variation, such as infection and maternal vitamin D levels, are potentially amendable to intervention.

  4. A genome-wide Asian genetic map and ethnic comparison: The GENDISCAN study

    Directory of Open Access Journals (Sweden)

    Sung Joohon

    2008-11-01

    Full Text Available Abstract Background Genetic maps provide specific positions of genetic markers, which are required for performing genetic studies. Linkage analyses of Asian families have been performed with Caucasian genetic maps, since appropriate genetic maps of Asians were not available. Different ethnic groups may have different recombination rates as a result of genomic variations, which would generate misspecification of the genetic map and reduce the power of linkage analyses. Results We constructed the genetic map of a Mongolian population in Asia with CRIMAP software. This new map, called the GENDISCAN map, is based on genotype data collected from 1026 individuals of 73 large Mongolian families, and includes 1790 total and 1500 observable meioses. The GENDISCAN map provides sex-averaged and sex-specific genetic positions of 1039 microsatellite markers in Kosambi centimorgans (cM with physical positions. We also determined 95% confidence intervals of genetic distances of the adjacent marker intervals. Genetic lengths of the whole genome, chromosomes and adjacent marker intervals are compared with those of Rutgers Map v.2, which was constructed based on Caucasian populations (Centre d'Etudes du Polymorphisme Humain (CEPH and Icelandic families by mapping methods identical to those of the GENDISCAN map, CRIMAP software and the Kosambi map function. Mongolians showed approximately 1.9 fewer recombinations per meiosis than Caucasians. As a result, genetic lengths of the whole genome and chromosomes of the GENDISCAN map are shorter than those of Rutgers Map v.2. Thirty-eight marker intervals differed significantly between the Mongolian and Caucasian genetic maps. Conclusion The new GENDISCAN map is applicable to the genetic study of Asian populations. Differences in the genetic distances between the GENDISCAN and Caucasian maps could facilitate elucidation of genomic variations between different ethnic groups.

  5. Genetic analysis of metabolites in apple fruits indicates an mQTL hotspot for phenolic compounds on linkage group 16

    NARCIS (Netherlands)

    Khan, S.A.; Chibon, P.Y.F.R.P.; Vos, de R.C.H.; Schipper, B.A.; Walraven, A.E.J.; Beekwilder, M.J.; Dijk, van T.; Finkers, H.J.; Visser, R.G.F.; Weg, van de W.E.; Bovy, A.G.; Cestaro, A.; Velasco, R.; Jacobsen, E.; Schouten, H.J.

    2012-01-01

    Apple (Malus×domestica Borkh) is among the main sources of phenolic compounds in the human diet. The genetic basis of the quantitative variations of these potentially beneficial phenolic compounds was investigated. A segregating F(1) population was used to map metabolite quantitative trait loci (mQT

  6. Studies on the Pathophysiology and Genetic Basis of Migraine

    Science.gov (United States)

    Gasparini, Claudia F; Sutherland, Heidi G.; Griffiths, Lyn R

    2013-01-01

    Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies. PMID:24403849

  7. Linkage Disequilibrium Estimation of Effective Population Size with Immigrants from Divergent Populations: A Case Study on Spanish Mackerel (Scomberomorus commerson).

    Science.gov (United States)

    Macbeth, Gilbert Michael; Broderick, Damien; Buckworth, Rik C; Ovenden, Jennifer R

    2013-03-11

    Estimates of genetic effective population size (Ne) using molecular markers are a potentially useful tool for the management of endangered through to commercial species. But, pitfalls are predicted when the effective size is large, as estimates require large numbers of samples from wild populations for statistical validity. Our simulations showed that linkage disequilibrium estimates of Ne up to 10,000 with finite confidence limits can be achieved with sample sizes around 5000. This was deduced from empirical allele frequencies of seven polymorphic microsatellite loci in a commercially harvested fisheries species, the narrow barred Spanish mackerel (Scomberomorus commerson). As expected, the smallest standard deviation of Ne estimates occurred when low frequency alleles were excluded. Additional simulations indicated that the linkage disequilibrium method was sensitive to small numbers of genotypes from cryptic species or conspecific immigrants. A correspondence analysis algorithm was developed to detect and remove outlier genotypes that could possibly be inadvertently sampled from cryptic species or non-breeding immigrants from genetically separate populations. Simulations demonstrated the value of this approach in Spanish mackerel data. When putative immigrants were removed from the empirical data, 95% of the Ne estimates from jacknife resampling were above 24,000.

  8. Linkage study of nonsyndromic cleft lip with or without cleft palate using candidate genes and mapped polymorphic markers

    Energy Technology Data Exchange (ETDEWEB)

    Stein, J.D.; Nelson, L.D.; Conner, B.J. [Univ. of Texas, Houston (United States)] [and others

    1994-09-01

    Nonsyndromic cleft lip with or without cleft palate (CL(P)) involves fusion or growth failure of facial primordia during development. Complex segregation analysis of clefting populations suggest that an autosomal dominant gene may play a role in this common craniofacial disorder. We have ascertained 16 multigenerational families with CL(P) and tested linkage to 29 candidate genes and 139 mapped short tandem repeat markers. The candidate genes were selected based on their expression in craniofacial development or were identified through murine models. These include: TGF{alpha}, TGF{beta}1, TGF{beta}2, TGF{beta}3, EGF, EGFR, GRAS, cMyc, FGFR, Jun, JunB, PDFG{alpha}, PDGF{beta}, IGF2R, GCR Hox7, Hox8, Hox2B, twirler, 5 collagen and 3 extracellular matrix genes. Linkage was tested assuming an autosomal dominant model with sex-specific decreased penetrance. Linkage to all of the candidate loci was excluded in 11 families. RARA was tested and was not informative. However, haplotype analysis of markers flanking RARA on 17q allowed exclusion of this candidate locus. We have previously excluded linkage to 61 STR markers in 11 families. Seventy-eight mapped short tandem repeat markers have recently been tested in 16 families and 30 have been excluded. The remaining are being analyzed and an exclusion map is being developed based on the entire study results.

  9. DEVELOPMENT OF ENZYME-LINKAGE IMMUNOSORBENT ASSAY AGAINST TYPE B OF CLOSTRIDIUM BOTULINUM: A PRELIMINARY STUDY

    Directory of Open Access Journals (Sweden)

    S. N. Depamede

    2011-12-01

    Full Text Available Clostridium botulinum neurotoxin (BoNTs is one of the causes of economic loss in the livestock industry. This economic loss would be as a direct result when animals poisoned by BoNTs or indirectly when the livestock products are contaminated by BoNTs, which end up with the products are banned by authority. Therefore a routine surveillance of BoNTs in the farm and in livestock product processing industry is urgently needed. One of the most relatively quick and accurate methods to perform a routine detection of the presence of BoNTs is enzyme-linkage immunosorbant assay (ELISA. In this article we describe the results of the development of ELISA, using polyclonal antibodies against BoNTs-B produced locally. Antibodies were generated from six Balb/c mice with standard immunological methods. Mice were immunized three times for a period of 8 weeks with a commercial type B Clostridium botulinum toxoid at a dose of 100 ng per mouse per injection. The resulting antibody was purified by a combination of ammonium sulfate precipitation 50% (w/v technique and a protein A column method. The results of this preliminary study indicated that the developed ELISA method capable of detecting type B Clostridium botulinum toxin up to 1.0 ng/ml.

  10. Linkage of the cholesterol 7α-hydroxylase gene and low-density lipoprotein cholesterol conditional on apolipoprotein E association: the National Heart, Lung, and Blood Institute Family Heart Study

    Institute of Scientific and Technical Information of China (English)

    Jing-Ping Lin; Richard H. Myers; Laura Almasy; Hilary H. Coon; Donna K. Arnett; Yuling Hong; Steven C. Hunt

    2005-01-01

    Background Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7α-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism. Methods Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used. Results The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.Conclusion Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.

  11. Comparative analysis of premature mortality among urban immigrants in Bremen, Germany: a retrospective register-based linkage study

    OpenAIRE

    Makarova, Nataliya; Brand, Tilman; Brünings-Kuppe, Claudia; Pohlabeln, Hermann; Luttmann, Sabine

    2016-01-01

    Objectives The main objective of this study was to explore differences in mortality patterns among two large immigrant groups in Germany: one from Turkey and the other from the former Soviet Union (FSU). To this end, we investigated indicators of premature mortality. Design This study was conducted as a retrospective population-based study based on mortality register linkage. Using mortality data for the period 2004–2010, we calculated age-standardised death rates (SDR) and standardised morta...

  12. A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions

    Science.gov (United States)

    Oikkonen, J.; Huang, Y.; Onkamo, P.; Ukkola-Vuoti, L.; Raijas, P.; Karma, K.; Vieland, V. J.; Järvelä, I.

    2014-01-01

    Humans have developed the perception, production and processing of sounds into the art of music. A genetic contribution to these skills of musical aptitude has long been suggested. We performed a genome-wide scan in 76 pedigrees (767 individuals) characterized for the ability to discriminate pitch (SP), duration (ST) and sound patterns (KMT), which are primary capacities for music perception. Using the Bayesian linkage and association approach implemented in program package KELVIN, especially designed for complex pedigrees, several SNPs near genes affecting the functions of the auditory pathway and neurocognitive processes were identified. The strongest association was found at 3q21.3 (rs9854612) with combined SP, ST and KMT test scores (COMB). This region is located a few dozen kilobases upstream of the GATA binding protein 2 (GATA2) gene. GATA2 regulates the development of cochlear hair cells and the inferior colliculus (IC), which are important in tonotopic mapping. The highest probability of linkage was obtained for phenotype SP at 4p14, located next to the region harboring the protocadherin 7 gene, PCDH7. Two SNPs rs13146789 and rs13109270 of PCDH7 showed strong association. PCDH7 has been suggested to play a role in cochlear and amygdaloid complexes. Functional class analysis showed that inner ear and schizophrenia related genes were enriched inside the linked regions. This study is the first to show the importance of auditory pathway genes in musical aptitude. PMID:24614497

  13. Sustainability inter-linkages in reporting vindeicated: a study of European companies

    NARCIS (Netherlands)

    Lozano, R.

    2013-01-01

    Recently, there has been a rapid growth in company sustainability reporting, as well as an improvement in quality of reports. A number of guidelines have been instrumental in this process; however, they still do not consider the importance of the inter-linkages and synergies among the different indi

  14. Additional support for schizophrenia linkage on chromosomes 6 and 8 : A multicenter study

    NARCIS (Netherlands)

    Levinson, DF; Wildenauer, DB; Schwab, SG; Albus, M; Hallmayer, J; Lerer, B; Maier, W; Blackwood, D; Muir, W; StClair, D; Morris, S; Moises, HW; Yang, L; Kristbjarnarson, H; Helgason, T; Wiese, C; Collier, DA; Holmans, P; Daniels, J; Rees, M; Asherson, P; Roberts, Q; Cardno, A; Arranz, MJ; Vallada, H; McGuffin, D; Owen, MJ; Pulver, AE; Antonarakis, SE; Babb, R; Blouin, JL; DeMarchi, N; Dombroski, B; Housman, D; Karayiorgou, M; Ott, J; Kasch, L; Kazazian, H; Lasseter, VK; Loetscher, E; Luebbert, H; Nestadt, G; Ton, C; Wolyniec, PS; Laurent, C; deChaldee, M; Thibaut, F; Jay, M; Samolyk, D; Petit, M; Campion, D; Mallet, J; Straub, RE; MacLean, CJ; Easter, SM; ONeill, FA; Walsh, D; Kendler, KS; Gejman, PV; Gershon, E; Badner, J; Beshah, E; Zhang, J; Riley, BP; Rajagopalan, S; MogudiCarter, M; Jenkins, T; Williamson, R; DeLisi, LE; Garner, C; Kelly, M; LeDuc, C; Cardon, L; Lichter, J; Harris, T; Loftus, J; Shields, G; Comasi, M; Vita, A; Smith, A; Dann, J; Joslyn, G; Gurling, H; Kalsi, G; Brynjolfsson, J; Curtis, D; Sigmundsson, T; Butler, R; Read, T; Murphy, P; Chen, ACH; Petursson, H; Byerley, B; Hoff, M; Holik, J; Coon, H; Nancarrow, DJ; Crowe, RR; Andreasen, N; Silverman, JM; Mohs, RC; Siever, LJ; Endicott, J; Sharpe, L; Lennon, DP; Hayward, NK; Sandkuijl, LA; Mowry, BJ; Aschauer, HN; Meszaros, K; Lenzinger, E; Fuchs, K; Heiden, AM; Kruglyak, L; Daly, MJ; Matise, TC

    1996-01-01

    In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hop

  15. Sustainability inter-linkages in reporting vindeicated: a study of European companies

    NARCIS (Netherlands)

    Lozano, R.

    2013-01-01

    Recently, there has been a rapid growth in company sustainability reporting, as well as an improvement in quality of reports. A number of guidelines have been instrumental in this process; however, they still do not consider the importance of the inter-linkages and synergies among the different

  16. A combined functional and structural genomics approach identified an EST-SSR marker with complete linkage to the Ligon lintless-2 genetic locus in cotton (Gossypium hirsutum L.

    Directory of Open Access Journals (Sweden)

    Tang Yuhong

    2011-09-01

    Full Text Available Abstract Background Cotton fiber length is an important quality attribute to the textile industry and longer fibers can be more efficiently spun into yarns to produce superior fabrics. There is typically a negative correlation between yield and fiber quality traits such as length. An understanding of the regulatory mechanisms controlling fiber length can potentially provide a valuable tool for cotton breeders to improve fiber length while maintaining high yields. The cotton (Gossypium hirsutum L. fiber mutation Ligon lintless-2 is controlled by a single dominant gene (Li2 that results in significantly shorter fibers than a wild-type. In a near-isogenic state with a wild-type cotton line, Li2 is a model system with which to study fiber elongation. Results Two near-isogenic lines of Ligon lintless-2 (Li2 cotton, one mutant and one wild-type, were developed through five generations of backcrosses (BC5. An F2 population was developed from a cross between the two Li2 near-isogenic lines and used to develop a linkage map of the Li2 locus on chromosome 18. Five simple sequence repeat (SSR markers were closely mapped around the Li2 locus region with two of the markers flanking the Li2 locus at 0.87 and 0.52 centimorgan. No apparent differences in fiber initiation and early fiber elongation were observed between the mutant ovules and the wild-type ones. Gene expression profiling using microarrays suggested roles of reactive oxygen species (ROS homeostasis and cytokinin regulation in the Li2 mutant phenotype. Microarray gene expression data led to successful identification of an EST-SSR marker (NAU3991 that displayed complete linkage to the Li2 locus. Conclusions In the field of cotton genomics, we report the first successful conversion of gene expression data into an SSR marker that is associated with a genomic region harboring a gene responsible for a fiber trait. The EST-derived SSR marker NAU3991 displayed complete linkage to the Li2 locus on

  17. EBL-1, a putative erythrocyte binding protein of Plasmodium falciparum, maps within a favored linkage group in two genetic crosses.

    Science.gov (United States)

    Peterson, D S; Wellems, T E

    2000-01-05

    The Duffy binding-like (DBL) superfamily of Plasmodium falciparum encompasses genes which encode ligands for host cell receptors. This superfamily includes two distinct groups of genes, the var genes which encode antigenically variant cytoadherence proteins (PfEMP1), and the eba-175 gene which encodes a glycophorin A binding protein involved in erythrocyte invasion. Here we describe another DBL superfamily member related to eba-175, the ebl-1 gene. Like the eba-175 gene, ebl-1 is a single copy gene encoding DBL domains that have sequences and an overall arrangement distinct from var genes. The inheritance of ebl-1 was found to be strongly favored in two genetic crosses in which one parental clone lacked a chromosome segment carrying the gene. A proliferation phenotype has been previously linked to the same chromosome segment in the first genetic cross. These results suggest that ebl-1 and eba-175 are related members of a multigene family involved in the invasion of erythrocytes by P. falciparum.

  18. Studies in genetic discrimination. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.

  19. A Comparative Analysis of Genetic Diversity and Structure in Jaguars (Panthera onca), Pumas (Puma concolor), and Ocelots (Leopardus pardalis) in Fragmented Landscapes of a Critical Mesoamerican Linkage Zone.

    Science.gov (United States)

    Wultsch, Claudia; Waits, Lisette P; Kelly, Marcella J

    2016-01-01

    With increasing anthropogenic impact and landscape change, terrestrial carnivore populations are becoming more fragmented. Thus, it is crucial to genetically monitor wild carnivores and quantify changes in genetic diversity and gene flow in response to these threats. This study combined the use of scat detector dogs and molecular scatology to conduct the first genetic study on wild populations of multiple Neotropical felids coexisting across a fragmented landscape in Belize, Central America. We analyzed data from 14 polymorphic microsatellite loci in 1053 scat samples collected from wild jaguars (Panthera onca), pumas (Puma concolor), and ocelots (Leopardus pardalis). We assessed levels of genetic diversity, defined potential genetic clusters, and examined gene flow for the three target species on a countrywide scale using a combination of individual- and population-based analyses. Wild felids in Belize showed moderate levels of genetic variation, with jaguars having the lowest diversity estimates (HE = 0.57 ± 0.02; AR = 3.36 ± 0.09), followed by pumas (HE = 0.57 ± 0.08; AR = 4.20 ± 0.16), and ocelots (HE = 0.63 ± 0.03; AR = 4.16 ± 0.08). We observed low to moderate levels of genetic differentiation for all three target species, with jaguars showing the lowest degree of genetic subdivision across the country, followed by ocelots and pumas. Although levels of genetic diversity and gene flow were still fairly high, we detected evidence of fine-scale genetic subdivision, indicating that levels of genetic connectivity for wild felids in Belize are likely to decrease if habitat loss and fragmentation continue at the current rate. Our study demonstrates the value of understanding fine-scale patterns of gene flow in multiple co-occurring felid species of conservation concern, which is vital for wildlife movement corridor planning and prioritizing future conservation and management efforts within human-impacted landscapes.

  20. A Comparative Analysis of Genetic Diversity and Structure in Jaguars (Panthera onca, Pumas (Puma concolor, and Ocelots (Leopardus pardalis in Fragmented Landscapes of a Critical Mesoamerican Linkage Zone.

    Directory of Open Access Journals (Sweden)

    Claudia Wultsch

    Full Text Available With increasing anthropogenic impact and landscape change, terrestrial carnivore populations are becoming more fragmented. Thus, it is crucial to genetically monitor wild carnivores and quantify changes in genetic diversity and gene flow in response to these threats. This study combined the use of scat detector dogs and molecular scatology to conduct the first genetic study on wild populations of multiple Neotropical felids coexisting across a fragmented landscape in Belize, Central America. We analyzed data from 14 polymorphic microsatellite loci in 1053 scat samples collected from wild jaguars (Panthera onca, pumas (Puma concolor, and ocelots (Leopardus pardalis. We assessed levels of genetic diversity, defined potential genetic clusters, and examined gene flow for the three target species on a countrywide scale using a combination of individual- and population-based analyses. Wild felids in Belize showed moderate levels of genetic variation, with jaguars having the lowest diversity estimates (HE = 0.57 ± 0.02; AR = 3.36 ± 0.09, followed by pumas (HE = 0.57 ± 0.08; AR = 4.20 ± 0.16, and ocelots (HE = 0.63 ± 0.03; AR = 4.16 ± 0.08. We observed low to moderate levels of genetic differentiation for all three target species, with jaguars showing the lowest degree of genetic subdivision across the country, followed by ocelots and pumas. Although levels of genetic diversity and gene flow were still fairly high, we detected evidence of fine-scale genetic subdivision, indicating that levels of genetic connectivity for wild felids in Belize are likely to decrease if habitat loss and fragmentation continue at the current rate. Our study demonstrates the value of understanding fine-scale patterns of gene flow in multiple co-occurring felid species of conservation concern, which is vital for wildlife movement corridor planning and prioritizing future conservation and management efforts within human-impacted landscapes.

  1. Do coxibs reduce prescription of gastroprotective agents? Results of a record linkage study

    Directory of Open Access Journals (Sweden)

    Violante Andrea

    2006-03-01

    Full Text Available Abstract Background Coxibs are claimed to be cost-effective drugs and reduced prescription of gastroprotective agents is assumed to be one of their major benefits. Real life prescription of these drugs may be substantially different than that considered in pharmacoeconomic analyses or claimed by drug companies, yet. Our objective was to evaluate whether coxibs were associated with reduced prescription of gastro-protective agents (GPAs, specifically proton pump inhibitors, H2 blockers and misoprostol compared to non selective NSAIDs. Methods A record-linkage study was performed using 2001 outpatient prescription data from the province of Modena (about 632,000 inhabitants, in Northern Italy. Logistic regression was used to calculate the odds ratio of GPA prescription for coxib and non-selective NSAID adult users (> 14 years. Three categories of users were further investigated: "acute", "chronic and "incident or new". Main outcome measures were same-day co-prescription and 30 days prescription of GPAs in coxibs and non selective NSAIDs users. To limit selection bias, data were adjusted for age, sex, DDD of coxibs and non selective NSAIDs received during 2001, DDD of GPAs and (for non-incident users DDD of NSAIDs received during the previous 4 years Results Same day co-prescription rates were similar considering the overall population and "acute" users. Chronic coxibs users instead showed higher co-prescription rates than chronic NSAIDs users (OR = 1.2, p Conclusion Assumptions made in pharmacoeconomic analyses on coxibs (lower GPA prescription associated with coxibs use may be overly optimistic. Claims made through cost-effectiveness data should be carefully interpreted, and mechanisms for attributing drug prices revised accordingly.

  2. [Linkage of large secondary and registry data sources with data of cohort studies : usage of a dual potential].

    Science.gov (United States)

    Jacobs, Svenja; Stallmann, Christoph; Pigeot, Iris

    2015-08-01

    Cohort studies provide the best evidence of all epidemiological observational studies for the identification of causal relationships between risk factors and diseases. However, this design may lead to drawbacks that may affect the validity and reliability of the results. This follows in particular from systematic errors, such as selection bias or recall bias. One possibility to avoid or counteract some of these drawbacks is to link primary data from cohort studies with secondary and register data. The linkage of these data may also be used for mutual validations. Data that were previously linked with primary data within the context of cohort studies in Germany were obtained from statutory health insurances and pensions as well as data from the Federal Employment Agency and cancer registries. All these data have two features in common: First, they all cover detailed information about a large population and over a long period of time. Second, all sources are in principle able to provide data on an individual level such that an individual data linkage, e.g. with primary data, is possible. However, use and linkage of each of these data sources are restricted by several limitations. These have to be accounted for as well as numerous legal restrictions that exist in Germany to especially prevent the misuse of social data.

  3. Progress in the Study of Molecular Genetic Improvements of Poplar in China

    Institute of Scientific and Technical Information of China (English)

    Shan-Zhi Lin; Zhi-Yi Zhang; Qian Zhang; Yuan-Zhen Lin

    2006-01-01

    The poplar is one of the most economically important and intensively studied tree species owing to its wide application in the timber industry and as a model material for the study of woody plants. The natural resource of poplars in China is replete. Over the past 10 years, the application of molecular biological techniques to genetic improvements in poplar species has been widely studied in China. Recent advances in molecular genetic improvements of poplar, including cDNA library construction, gene cloning and identification, genetic engineering, gene expression, genetic linkage map construction, mapping of quantitative trait loci (QTL) and molecular-assisted selection, are reviewed in the present paper. In addition, the application of modern biotechnology to molecular improvements in the genetic traits of the poplar and some unsolved problems are discussed.

  4. The genetics of alcoholism: identifying specific genes through family studies.

    Science.gov (United States)

    Edenberg, Howard J; Foroud, Tatiana

    2006-09-01

    Alcoholism is a complex disorder with both genetic and environmental risk factors. Studies in humans have begun to elucidate the genetic underpinnings of the risk for alcoholism. Here we briefly review strategies for identifying individual genes in which variations affect the risk for alcoholism and related phenotypes, in the context of one large study that has successfully identified such genes. The Collaborative Study on the Genetics of Alcoholism (COGA) is a family-based study that has collected detailed phenotypic data on individuals in families with multiple alcoholic members. A genome-wide linkage approach led to the identification of chromosomal regions containing genes that influenced alcoholism risk and related phenotypes. Subsequently, single nucleotide polymorphisms (SNPs) were genotyped in positional candidate genes located within the linked chromosomal regions, and analyzed for association with these phenotypes. Using this sequential approach, COGA has detected association with GABRA2, CHRM2 and ADH4; these associations have all been replicated by other researchers. COGA has detected association to additional genes including GABRG3, TAS2R16, SNCA, OPRK1 and PDYN, results that are awaiting confirmation. These successes demonstrate that genes contributing to the risk for alcoholism can be reliably identified using human subjects.

  5. Genome wide linkage disequilibrium in Chinese asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm: implications for domestication history and genome wide association studies.

    Science.gov (United States)

    Xu, P; Wu, X; Wang, B; Luo, J; Liu, Y; Ehlers, J D; Close, T J; Roberts, P A; Lu, Z; Wang, S; Li, G

    2012-07-01

    Association mapping of important traits of crop plants relies on first understanding the extent and patterns of linkage disequilibrium (LD) in the particular germplasm being investigated. We characterize here the genetic diversity, population structure and genome wide LD patterns in a set of asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm from China. A diverse collection of 99 asparagus bean and normal cowpea accessions were genotyped with 1127 expressed sequence tag-derived single nucleotide polymorphism markers (SNPs). The proportion of polymorphic SNPs across the collection was relatively low (39%), with an average number of SNPs per locus of 1.33. Bayesian population structure analysis indicated two subdivisions within the collection sampled that generally represented the 'standard vegetable' type (subgroup SV) and the 'non-standard vegetable' type (subgroup NSV), respectively. Level of LD (r(2)) was higher and extent of LD persisted longer in subgroup SV than in subgroup NSV, whereas LD decayed rapidly (0-2 cM) in both subgroups. LD decay distance varied among chromosomes, with the longest (≈ 5 cM) five times longer than the shortest (≈ 1 cM). Partitioning of LD variance into within- and between-subgroup components coupled with comparative LD decay analysis suggested that linkage group 5, 7 and 10 may have undergone the most intensive epistatic selection toward traits favorable for vegetable use. This work provides a first population genetic insight into domestication history of asparagus bean and demonstrates the feasibility of mapping complex traits by genome wide association study in asparagus bean using a currently available cowpea SNPs marker platform.

  6. Prenatal diagnosis of the carbohydrate-deficient glycoprotein syndrome type 1A (CDG1A) by a combination of enzymology and genetic linkage analysis after amniocentesis or chorionic villus sampling.

    Science.gov (United States)

    Charlwood, J; Clayton, P; Keir, G; Mian, N; Young, E; Winchester, B

    1998-07-01

    Two pregnancies at risk for the carbohydrate-deficient glycoprotein syndrome Type 1A (CDG1A, phosphomannomutase deficient) were monitored by enzyme and genetic linkage analyses. The index case in both families had a proven deficiency of phosphomannomutase (PMM). An unaffected fetus was predicted in family 1 following amniocentesis. Normal PMM activity was found in cultured amniotic fluid cells and there was no elevation of lysosomal enzymes in the amniotic fluid. Genetic linkage analysis using microsatellite markers closely linked to the CDG1A gene confirmed this prediction. A healthy child was born. In the second family direct assay of chorionic villi showed a profound deficiency of PMM and genetic linkage analysis showed the fetus to have the same haplotype as the proband. The pregnancy was terminated and a deficiency of PMM was confirmed in cultured fibroblasts from the fetus. Reliable prenatal diagnosis of CDG Type 1A (PMM-deficient) can be achieved by a combination of biochemical and molecular genetic tests.

  7. Barriers and facilitators to linkage to ART in primary care: a qualitative study of patients and providers in Blantyre, Malawi

    Directory of Open Access Journals (Sweden)

    Peter MacPherson

    2012-12-01

    Full Text Available Introduction: Linkage from HIV testing and counselling (HTC to initiation of antiretroviral therapy (ART is suboptimal in many national programmes in sub-Saharan Africa, leading to delayed initiation of ART and increased risk of death. Reasons for failure of linkage are poorly understood. Methods: Semi-structured qualitative interviews were undertaken with health providers and HIV-positive primary care patients as part of a prospective cohort study at primary health centres in Blantyre, Malawi. Patients successful and unsuccessful in linking to ART were included. Results: Progression through the HIV care pathway was strongly influenced by socio-cultural norms, particularly around the perceived need to regain respect lost during a period of visibly declining health. Capacity to call upon the support of networks of families, friends and employers was a key determinant of successful progression. Over-busy clinics, non-functioning laboratories and unsuitable tools used for ART eligibility assessment (WHO clinical staging system and centralized CD4 count measurement were important health systems determinants of drop-out. Conclusions: Key interventions that could rapidly improve linkage include guarantee of same-day, same-clinic ART eligibility assessments; utilization of the support offered by peer-groups and community health workers; and integration of HTC and ART programmes.

  8. Combined Linkage and Association Studies Show that HLA Class II Variants Control Levels of Antibodies against Epstein-Barr Virus Antigens

    Science.gov (United States)

    Cobat, Aurélie; Guergnon, Julien; Brice, Pauline; Fermé, Christophe; Carde, Patrice; Hermine, Olivier; Pendeven, Catherine Le-; Amiel, Corinne; Taoufik, Yassine; Alcaïs, Alexandre; Theodorou, Ioannis; Besson, Caroline; Abel, Laurent

    2014-01-01

    Over 95% of the adult population worldwide is infected with Epstein-Barr virus (EBV). EBV infection is associated with the development of several cancers, including Hodgkin lymphoma (HL). Elevated levels of anti-EBV antibodies have been associated with increased risk of HL. There is growing evidence that genetic factors control the levels of antibodies against EBV antigens. Here, we conducted linkage and association studies to search for genetic factors influencing either anti-viral capsid antigen (VCA) or anti-Epstein Barr nuclear antigen-1 (EBNA-1) IgG levels in a unique cohort of 424 individuals of European origin from 119 French families recruited through a Hodgkin lymphoma (HL) patient. No major locus controlling anti-VCA antibody levels was identified. However, we found that the HLA region influenced anti-EBNA-1 IgG titers. Refined association studies in this region identified a cluster of HLA class II variants associated with anti-EBNA-1 IgG titers (e.g. p = 5×10–5 for rs9268403). The major allele of rs9268403 conferring a predisposition to high anti-EBNA-1 antibody levels was also associated with an increased risk of HL (p = 0.02). In summary, this study shows that HLA class II variants influenced anti-EBNA-1 IgG titers in a European population. It further shows the role of the same variants in the risk of HL. PMID:25025336

  9. Combined linkage and association studies show that HLA class II variants control levels of antibodies against Epstein-Barr virus antigens.

    Directory of Open Access Journals (Sweden)

    Vincent Pedergnana

    Full Text Available Over 95% of the adult population worldwide is infected with Epstein-Barr virus (EBV. EBV infection is associated with the development of several cancers, including Hodgkin lymphoma (HL. Elevated levels of anti-EBV antibodies have been associated with increased risk of HL. There is growing evidence that genetic factors control the levels of antibodies against EBV antigens. Here, we conducted linkage and association studies to search for genetic factors influencing either anti-viral capsid antigen (VCA or anti-Epstein Barr nuclear antigen-1 (EBNA-1 IgG levels in a unique cohort of 424 individuals of European origin from 119 French families recruited through a Hodgkin lymphoma (HL patient. No major locus controlling anti-VCA antibody levels was identified. However, we found that the HLA region influenced anti-EBNA-1 IgG titers. Refined association studies in this region identified a cluster of HLA class II variants associated with anti-EBNA-1 IgG titers (e.g. p = 5×10(-5 for rs9268403. The major allele of rs9268403 conferring a predisposition to high anti-EBNA-1 antibody levels was also associated with an increased risk of HL (p = 0.02. In summary, this study shows that HLA class II variants influenced anti-EBNA-1 IgG titers in a European population. It further shows the role of the same variants in the risk of HL.

  10. Construction of a genetic linkage map for tetraploid hybrid wheatgrass using a SSR molecular marker%利用 SSR 分子标记构建四倍体杂交冰草的遗传连锁图谱

    Institute of Scientific and Technical Information of China (English)

    姜志艳; 于肖夏; 于卓; 张志成; 石悦; 姜超

    2016-01-01

    为构建四倍体杂交冰草分子遗传连锁图谱,对深入开展冰草产量、抗性等重要性状的 QTL 定位及分子标记辅助育种提供依据,以四倍体杂种 F2分离群体的347个单株及亲本蒙古冰草和航道冰草为材料,采用 SSR 分子标记技术和 Joinmap 4.0软件进行了遗传作图研究。试验从256对 SSR 引物中筛选出条带清晰稳定、多态性丰富的适宜引物30对,PCR 扩增得到224个 SSR 标记位点,平均每对引物扩增出7.47个位点,其中多态性标记位点185个,占82.6%。偏分离分析显示,在185个 SSR 多态性标记位点中有24个标记产生偏分离,占13.0%,符合植物遗传作图时通常偏分离标记比率<30%的要求,可用于遗传作图。构建了1张四倍体杂交冰草的分子遗传连锁框架图谱,该图谱包含14个连锁群、185个标记,其长度范围在123.0~202.6 cM 之间,连锁群 LG4最长、LG12最短,各连锁群的平均长度167.32 cM,覆盖基因组总长度2342.5 cM,标记间的平均距离12.66 cM。%To establish a genetic linkage map in tetraploid hybrid wheatgrass genetic mapping was conducted u-sing a simple sequence repeats (SSR)molecular marker technique with ‘Joinmap’4.0 software.347 individu-als from the F2 segregating population and their parents were utilized,this helped lay the foundation for further study of marker-assisted breeding,and quantitative trait locus (QTL)location of important traits in wheat-grass,such as disease resistance and yield.Thirty optimal primers with clear,stable and high polymorphic bands were screened from 256 tested SSR primers.A total of 224 SSR loci were obtained from polymerase chain reaction (PCR)amplification with an average of 7.47 loci per primer,of which 185 were polymorphic lo-ci,accounting for 82.6% of all loci.Segregation distortion analysis showed that a total of 24 loci were distort-ed,accounted for 13.0% of all (185)polymorphic

  11. The quality of Indigenous identification in administrative health data in Australia: insights from studies using data linkage

    Directory of Open Access Journals (Sweden)

    Thompson Sandra C

    2012-11-01

    Full Text Available Abstract Background Missing or incorrect Indigenous status in health records hinders monitoring of Indigenous health indicators. Linkage of administrative data has been used to improve the ascertainment of Indigenous status. Data linkage was pioneered in Western Australia (WA and is now being used in other Australian states. This systematic review appraises peer-reviewed Australian studies that used data linkage to elucidate the impact of under-ascertainment of Indigenous status on health indicators. Methods A PubMed search identified eligible studies that used Australian linked data to interrogate Indigenous identification using more than one identifier and interrogated the impact of the different identifiers on estimation of Indigenous health indicators. Results Eight papers were included, five from WA and three from New South Wales (NSW. The WA papers included a self-identified Indigenous community cohort and showed improved identification in hospital separation data after 2000. In CVD hospitalised patients (2000–05, under-identification was greater in urban residents, older people and socially more advantaged Indigenous people, with varying algorithms giving different estimates of under-count. Age-standardised myocardial infarction incidence rates (2000–2004 increased by about 10%-15% with improved identification. Under-ascertainment of Indigenous identification overestimated secular improvements in life expectancy and mortality whereas correcting infectious disease notifications resulted in lower Indigenous/ non-Indigenous rate ratios. NSW has a history of poor Indigenous identification in administrative data systems, but the NSW papers confirmed the usefulness of data linkage for improving Indigenous identification and the potential for very different estimates of Indigenous disease indicators depending upon the algorithm used for identification. Conclusions Under-identification of Indigenous status must be addressed in health analyses

  12. Pearls and pitfalls in genetic studies of migraine.

    Science.gov (United States)

    Eising, Else; de Vries, Boukje; Ferrari, Michel D; Terwindt, Gisela M; van den Maagdenberg, Arn M J M

    2013-06-01

    Migraine is a prevalent neurovascular brain disorder with a strong genetic component, and different methodological approaches have been implemented to identify the genes involved. This review focuses on pearls and pitfalls of these approaches and genetic findings in migraine. Common forms of migraine (i.e. migraine with and without aura) are thought to have a polygenic make-up, whereas rare familial hemiplegic migraine (FHM) presents with a monogenic pattern of inheritance. Until a few years ago only studies in FHM yielded causal genes, which were identified by a classical linkage analysis approach. Functional analyses of FHM gene mutations in cellular and transgenic animal models suggest abnormal glutamatergic neurotransmission as a possible key disease mechanism. Recently, a number of genes were discovered for the common forms of migraine using a genome-wide association (GWA) approach, which sheds first light on the pathophysiological mechanisms involved. Novel technological strategies such as next-generation sequencing, which can be implemented in future genetic migraine research, may aid the identification of novel FHM genes and promote the search for the missing heritability of common migraine.

  13. Gene set analysis for interpreting genetic studies

    DEFF Research Database (Denmark)

    Pers, Tune H

    2016-01-01

    Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways and func......Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways...

  14. Hospitalized prevalence and 5-year mortality for IBD:Record linkage study

    Institute of Scientific and Technical Information of China (English)

    Lori; A; Button; Stephen; E; Roberts; Michael; J; Goldacre; Ashley; Akbari; Sarah; E; Rodgers; John; G; Williams

    2010-01-01

    AIM:To establish the hospitalized prevalence of severe Crohn's disease(CD) and ulcerative colitis(UC) in Wales from 1999 to 2007;and to investigate long-term mortality after hospitalization and associations with social deprivation and other socio-demographic factors.METHODS:Record linkage of administrative inpatient and mortality data for 1467 and 1482 people hospitalised as emergencies for ≥ 3d for CD and UC,respectively.The main outcome measures were hospitalized prevalence,mortality rates and standardize...

  15. Planned Repeat Cesarean Section at Term and Adverse Childhood Health Outcomes: A Record-Linkage Study.

    Directory of Open Access Journals (Sweden)

    Mairead Black

    2016-03-01

    Full Text Available Global cesarean section (CS rates range from 1% to 52%, with a previous CS being the commonest indication. Labour following a previous CS carries risk of scar rupture, with potential for offspring hypoxic brain injury, leading to high rates of repeat elective CS. However, the effect of delivery by CS on long-term outcomes in children is unclear. Increasing evidence suggests that in avoiding exposure to maternal bowel flora during labour or vaginal birth, offspring delivered by CS may be adversely affected in terms of energy uptake from the gut and immune development, increasing obesity and asthma risks, respectively. This study aimed to address the evidence gap on long-term childhood outcomes following repeat CS by comparing adverse childhood health outcomes after (1 planned repeat CS and (2 unscheduled repeat CS with those that follow vaginal birth after CS (VBAC.A data-linkage cohort study was performed. All second-born, term, singleton offspring delivered between 1 January 1993 and 31 December 2007 in Scotland, UK, to women with a history of CS (n = 40,145 were followed up until 31 January 2015. Outcomes assessed included obesity at age 5 y, hospitalisation with asthma, learning disability, cerebral palsy, and death. Cox regression and binary logistic regression were used as appropriate to compare outcomes following planned repeat CS (n = 17,919 and unscheduled repeat CS (n = 8,847 with those following VBAC (n = 13,379. Risk of hospitalisation with asthma was greater following both unscheduled repeat CS (3.7% versus 3.3%, adjusted hazard ratio [HR] 1.18, 95% CI 1.05-1.33 and planned repeat CS (3.6% versus 3.3%, adjusted HR 1.24, 95% CI 1.09-1.42 compared with VBAC. Learning disability and death were more common following unscheduled repeat CS compared with VBAC (3.7% versus 2.3%, adjusted odds ratio 1.64, 95% CI 1.17-2.29, and 0.5% versus 0.4%, adjusted HR 1.50, 95% CI 1.00-2.25, respectively. Risk of obesity at age 5 y and risk of cerebral

  16. Quantitative genetic studies of antisocial behaviour.

    Science.gov (United States)

    Viding, Essi; Larsson, Henrik; Jones, Alice P

    2008-08-12

    This paper will broadly review the currently available twin and adoption data on antisocial behaviour (AB). It is argued that quantitative genetic research can make a significant contribution to further the understanding of how AB develops. Genetically informative study designs are particularly useful for investigating several important questions such as whether: the heritability estimates vary as a function of assessment method or gender; the relative importance of genetic and environmental influences varies for different types of AB; the environmental risk factors are truly environmental; and genetic vulnerability influences susceptibility to environmental risk. While the current data are not yet directly translatable for prevention and treatment programmes, quantitative genetic research has concrete translational potential. Quantitative genetic research can supplement neuroscience research in informing about different subtypes of AB, such as AB coupled with callous-unemotional traits. Quantitative genetic research is also important in advancing the understanding of the mechanisms by which environmental risk operates.

  17. 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.

  18. Spindle pole mechanics studied in mitotic asters: dynamic distribution of spindle forces through compliant linkages.

    Science.gov (United States)

    Charlebois, Blake D; Kollu, Swapna; Schek, Henry T; Compton, Duane A; Hunt, Alan J

    2011-04-06

    During cell division, chromosomes must faithfully segregate to maintain genome integrity, and this dynamic mechanical process is driven by the macromolecular machinery of the mitotic spindle. However, little is known about spindle mechanics. For example, spindle microtubules are organized by numerous cross-linking proteins yet the mechanical properties of those cross-links remain unexplored. To examine the mechanical properties of microtubule cross-links we applied optical trapping to mitotic asters that form in mammalian mitotic extracts. These asters are foci of microtubules, motors, and microtubule-associated proteins that reflect many of the functional properties of spindle poles and represent centrosome-independent spindle-pole analogs. We observed bidirectional motor-driven microtubule movements, showing that microtubule linkages within asters are remarkably compliant (mean stiffness 0.025 pN/nm) and mediated by only a handful of cross-links. Depleting the motor Eg5 reduced this stiffness, indicating that Eg5 contributes to the mechanical properties of microtubule asters in a manner consistent with its localization to spindle poles in cells. We propose that compliant linkages among microtubules provide a mechanical architecture capable of accommodating microtubule movements and distributing force among microtubules without loss of pole integrity-a mechanical paradigm that may be important throughout the spindle.

  19. High-Resolution Genome-Wide Linkage Mapping Identifies Susceptibility Loci for BMI in the Chinese Population

    DEFF Research Database (Denmark)

    Zhang, Dong Feng; Pang, Zengchang; Li, Shuxia

    2012-01-01

    The genetic loci affecting the commonly used BMI have been intensively investigated using linkage approaches in multiple populations. This study aims at performing the first genome-wide linkage scan on BMI in the Chinese population in mainland China with hypothesis that heterogeneity in genetic...... in western countries. Multiple loci showing suggestive linkage were found on chromosome 1 (lod score 2.38 at 242 cM), chromosome 8 (2.48 at 95 cM), and chromosome 14 (2.2 at 89.4 cM). The strong linkage identified in the Chinese subjects that is consistent with that found in populations of European origin...... could suggest the existence of evolutionarily preserved genetic mechanisms for BMI whereas the multiple suggestive loci could represent genetic effect from gene-environment interaction as a result of population-specific environmental adaptation....

  20. Lack of association or linkage disequilibrium between schizophrenia and polymorphisms in the 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes: family-based association study.

    Science.gov (United States)

    Ambrósio, Alda M; Kennedy, James L; Macciardi, Fabio; Coelho, Isabel; Soares, Maria J; Oliveira, Catarina R; Pato, Carlos N

    2004-07-01

    Genetic factors play a major role in the etiology of schizophrenia and disturbances of serotonergic pathways have been implicated in this disorder. The aim of the present study was to examine genetic association between schizophrenia and polymorphisms in the 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) autoreceptor genes in ninety trios from Portugal. No association or linkage disequilibrium was obtained between schizophrenia and 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes with both haplotype relative risk (HRR) and transmission disequilibrium test (TDT). Concerning 5-HT1Dbeta autoreceptor gene, also negative results was obtained in the analysis of the haplotypes with transmit. Thus, our data provide no support for the hypothesis that polymorphisms at 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) genes contributes to susceptibility to schizophrenia in the Portuguese population. Copyright 2004 Wiley-Liss, Inc.

  1. A genetic epidemiologic study of hemochromatosis

    NARCIS (Netherlands)

    O.T. Njajou (Omer)

    2002-01-01

    textabstractThe goal of genetic epidemiology is to study the genetic etiology of diseases. There were t\\vo main aims for the present thesis. The first aim was to study the effects of the hemochromatosis gene (HFE) mutations on serum iron levels and disease associated conditions. Secondly, we aimed a

  2. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  3. Power assessment for genetic association study of human longevity using offspring of long-lived subjects

    DEFF Research Database (Denmark)

    Tan, Qihua; Zhao, Jing Hua; Li, Shuxia;

    2010-01-01

    Recently, an indirect genetic association approach that compares genotype frequencies in offspring of long-lived subjects and offspring from random families has been introduced to study gene-longevity associations. Although the indirect genetic association has certain advantages over the direct...... and the proportional hazard model for generating individual lifespan. Family genotype data is generated using a genetic linkage program for given SNP allele frequency. Power is estimated by setting the type I error rate at 0.05 and by calculating the Armitage's chi-squared test statistic for 200 replicate samples...... for each setting of the specified allele risk and frequency parameters under different modes of inheritance and for different sample sizes. The indirect genetic association analysis is a valid approach for studying gene-longevity association, but the sample size requirement is about 3-4 time larger than...

  4. Quantitative genetic studies of antisocial behaviour

    OpenAIRE

    Viding, Essi; Larsson, Henrik; Jones, Alice P.

    2008-01-01

    This paper will broadly review the currently available twin and adoption data on antisocial behaviour (AB). It is argued that quantitative genetic research can make a significant contribution to further the understanding of how AB develops. Genetically informative study designs are particularly useful for investigating several important questions such as whether: the heritability estimates vary as a function of assessment method or gender; the relative importance of genetic and environmental ...

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

    Science.gov (United States)

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

    2013-01-01

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

  6. The -351A>G genetic polymorphism in the estrogen receptor alpha gene and risk of endometriosis: a case-control study

    Directory of Open Access Journals (Sweden)

    Reihaneh Asadi

    2015-03-01

    Conclusion: The results do not support the previous findings of an association between -351A>G genetic polymorphism in ESR1 gene and endometriosis. Therefore, comprehensive genetic approaches including linkage analyses and family-based tests, together with a number of replication studies with large sample size, are needed to make conclusive claims about the role of this genetic polymorphism in susceptibility to endometriosis.

  7. CURRENCY LINKAGES AMONG ASEAN

    OpenAIRE

    CHIN LEE; M. Azali

    2010-01-01

    The purpose of this study is to examine the potential linkages among ASEAN-5 currencies, in particular the possibility of a Singapore dollar bloc during the pre- and post-crisis periods by using the Johansen multivariate cointegration test and the Granger causality test. Significant nonstationarity and the presence of unit roots were documented for each currency under both study periods. Using ASEAN-4 exchange rates against the Singapore dollar, the Johansen cointegration test showed that the...

  8. Linkage study of DFNB3 responsible for hearing loss in human

    Directory of Open Access Journals (Sweden)

    Akhtar Ali

    2013-01-01

    Conclusion: Knowledge about the genetic causes of deafness provide insight into the variable expression of genes involved in this hereditary problem and may allow the prediction and prevention of associated health problems.

  9. 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...

  10. Transmission test for linkage disequilibrium: The insulin gene region and insulin-dependent diabetes mellitus (IDDM)

    Energy Technology Data Exchange (ETDEWEB)

    Spielman, R.S.; McGinnis, R.E. (Univ. of Pennsylvania School of Medicine, Philadelphia (United States)); Ewens, W.J. (Univ. of Pennsylvania, Philadelphia (United States))

    1993-03-01

    A population association has consistently been observed between insulin-dependent diabetes mellitus (IDDM) and the class 1 alleles of the region of tandem-repeat DNA (5[prime] flanking polymorphism [5[prime]FP])adjacent to the insulin gene on chromosome 11p. This finding suggests that the insulin gene region contains a gene or genes contributing to IDDM susceptibility. However, several studies that have sought to show linkage with IDDM by testing for cosegregation in affected sib pairs have failed to find evidence for linkage. As means for identifying genes for complex diseases, both the association and the affected-sib-pairs approaches have limitations. It is well known that population association between a disease and a genetic marker can arise as an artifact of population structure, even in the absence of linkage. On the other hand, linkage studies with modest numbers of affected sib pairs may fail to detect linkage, especially if there is linkage heterogeneity. The authors consider an alternative method to test for linkage with a genetic marker when population association has been found. Using data from families with at least one affected child, they evaluate the transmission of the associated marker allele from a heterozygous parent to an affected offspring. This approach has been used by several investigators, but the statistical properties of the method as a test for linkage have not been investigated. In the present paper they describe the statistical basis for this transmission test for linkage disequilibrium (transmission/disequilibrium test [TDT]). They then show the relationship of this test to tests of cosegregation that are based on the proportion of haplotypes or genes identical by descent in affected sibs. The TDT provides strong evidence for linkage between the 5[prime]FP and susceptibility to IDDM. 27 refs., 6 tabs.

  11. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    Directory of Open Access Journals (Sweden)

    Gonzalez-Neira Anna

    2007-08-01

    Full Text Available Abstract Background The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel, with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion Our results show the power increase that SNPs can supply in linkage studies.

  12. Genetic linkage in the horse. II. Distribution of male recombination estimates and the influence of age, breed and sex on recombination frequency.

    Science.gov (United States)

    Andersson, L; Sandberg, K

    1984-01-01

    In the present study an extensive amount of data, comprising more than 30,000 offspring in total, was analyzed to evaluate the influence of age and sex on the recombination frequency in the K-PGD segment of the equine linkage group (LG) I and the influence of age, breed and sex on recombination in the Al-Es segment of LG II. A highly significant sex difference is reported for both segments. Male and female recombination values in the K-PGD segment were estimated at 25.8 +/- 0.8 and 33.3 +/- 2.5%, respectively. Similarly, recombination was less frequent in the male (36.6 +/- 0.7%) than in the female (46.6 +/- 1.2%) in the Al-Es segment. Comparison of data from two Swedish horse breeds revealed no significant breed differences in either sex for recombination in the Al-Es segment. No evidence of an age effect was found in any segment or sex. The distribution of individual male recombination estimates was also investigated, and a significant heterogeneity among stallions was revealed in the K-PGD segment. The results are discussed in relation to previous studies on factors affecting recombination in mammals.

  13. STAKEHOLDER LINKAGES FOR SUSTAINABLE LAND ...

    African Journals Online (AJOL)

    Osondu

    stakeholder interactions for SLM in the study areas. Key words: Stakeholders; farmer-expert linkages; resource management; Ethiopia ... management practices in many parts of Africa. Farmers .... chosen with consideration of distance to the.

  14. Genomewide linkage analysis of stature in multiple populations reveals several regions with evidence of linkage to adult height.

    Science.gov (United States)

    Hirschhorn, J N; Lindgren, C M; Daly, M J; Kirby, A; Schaffner, S F; Burtt, N P; Altshuler, D; Parker, A; Rioux, J D; Platko, J; Gaudet, D; Hudson, T J; Groop, L C; Lander, E S

    2001-07-01

    Genomewide linkage analysis has been extremely successful at identification of the genetic variation underlying single-gene disorders. However, linkage analysis has been less successful for common human diseases and other complex traits in which multiple genetic and environmental factors interact to influence disease risk. We hypothesized that a highly heritable complex trait, in which the contribution of environmental factors was relatively limited, might be more amenable to linkage analysis. We therefore chose to study stature (adult height), for which heritability is approximately 75%-90% (Phillips and Matheny 1990; Carmichael and McGue 1995; Preece 1996; Silventoinen et al. 2000). We reanalyzed genomewide scans from four populations for which genotype and height data were available, using a variance-components method implemented in GENEHUNTER 2.0 (Pratt et al. 2000). The populations consisted of 408 individuals in 58 families from the Botnia region of Finland, 753 individuals in 183 families from other parts of Finland, 746 individuals in 179 families from Southern Sweden, and 420 individuals in 63 families from the Saguenay-Lac-St.-Jean region of Quebec. Four regions showed evidence of linkage to stature: 6q24-25, multipoint LOD score 3.85 at marker D6S1007 in Botnia (genomewide Pgenetically tractable and provide insight into the genetic architecture of complex traits.

  15. Exploring evidence-policy linkages in health research plans: A case study from six countries

    Directory of Open Access Journals (Sweden)

    Oladepo Oladimeji

    2008-03-01

    Full Text Available Abstract The complex evidence-policy interface in low and middle income country settings is receiving increasing attention. Future Health Systems (FHS: Innovations for Equity, is a research consortium conducting health systems explorations in six Asian and African countries: Bangladesh, India, China, Afghanistan, Uganda, and Nigeria. The cross-country research consortium provides a unique opportunity to explore the research-policy interface. Three key activities were undertaken during the initial phase of this five-year project. First, key considerations in strengthening evidence-policy linkages in health system research were developed by FHS researchers through workshops and electronic communications. Four key considerations in strengthening evidence-policy linkages are postulated: development context; research characteristics; decision-making processes; and stakeholder engagement. Second, these four considerations were applied to research proposals in each of the six countries to highlight features in the research plans that potentially strengthen the research-policy interface and opportunities for improvement. Finally, the utility of the approach for setting research priorities in health policy and systems research was reflected upon. These three activities yielded interesting findings. First, developmental consideration with four dimensions – poverty, vulnerabilities, capabilities, and health shocks – provides an entry point in examining research-policy interfaces in the six settings. Second, research plans focused upon on the ground realities in specific countries strengthens the interface. Third, focusing on research prioritized by decision-makers, within a politicized health arena, enhances chances of research influencing action. Lastly, early and continued engagement of multiple stakeholders, from local to national levels, is conducive to enhanced communication at the interface. The approach described has four main utilities: first

  16. Molecular mapping and characterization of genes governing time to flowering, seed weight, and plant height in an intraspecific genetic linkage map of chickpea (Cicer arietinum).

    Science.gov (United States)

    Jamalabadi, Javad Ghorbani; Saidi, Abbas; Karami, Ezzat; Kharkesh, Mehrab; Talebi, Reza

    2013-06-01

    Drought is the major constraint to chickpea productivity worldwide. Utilizing early flowering genotypes and larger seed size have been suggested as strategies for breeding in drought zones. Therefore, this study aimed to identify potential markers linked to days-to-flowering, 100-seed weight, and plant height in a chickpea intraspecific F(2:3) population derived from the cross ILC3279 × ICCV2. A closely linked marker (TA117) on linkage group LG3 was identified for the days-to-flowering trait, explaining 33% of the variation. In relation to plant height, a quantitative trait loci (QTL) was located in LG3, close to the Ts5 marker, that explained 29% of phenotypic variation. A QTL for 100-seed weight located in LG4, close to TA176, explained 51% of variation. The identification of a locus linked both to high 100-seed weight and days-to-flowering may account for the correlation observed between these traits in this and other breeding attempts.

  17. O uso da técnica de "Linkage" de sistemas de informação em estudos de coorte sobre mortalidade neonatal The use of the 'Linkage' of information systems in cohort studies of neonatal mortality

    Directory of Open Access Journals (Sweden)

    Marcia Furquim de Almeida

    1996-04-01

    Full Text Available Discute-se o uso da "linkage" dos Sistemas Oficiais de Informação de Nascido Vivo (SINASC e de Óbitos (SIM em estudos de mortalidade neonatal. Essa técnica baseia-se na "ligação" dos bancos de dados obtidos a partir das informações existentes nesses sistemas, o que possibilita o emprego de estudos do tipo de coorte. O estudo foi realizado no Município de Santo André, Região Metropolitana de São Paulo, Brasil. São apresentados os cuidados metodológicos que foram empregados para evitar a presença de viéses de seleção e de efeito, que podem ocorrer. O uso da "linkage" mostrou-se operacionalmente viável, permitindo obter as probabilidades de morte e os riscos relativos dos nascidos vivos, expostos e não expostos, às variáveis que são objeto de registro na declaração de nascido vivo, identificando-se, desta maneira, os recém-nascidos de risco. Essa técnica, de baixo custo operacional, visto que utiliza dados já registrados, permite um dimensionamento mais adequado da assistência pré-natal e ao parto.The utilization of record linkage of the mortality and birth information systems in studies of neonatal mortality is presented. The record linkage was used to obtain a cohort of live births and neonatal deaths in Santo André county, located within greater S. Paulo, in 1992. The procedures applied in order to avoid selection and effect biases, are discussed. The use of linked data allows the probabilities of neonatal deaths according to the exposure status of the variables which are registered on the birth certificate, and the identification of the live born at risk, to be calculated. Another advantage of the record linkage is the low financial cost of this type of study, because it uses information already registered.

  18. A computer model allowing maintenance of large amounts of genetic variability in Mendelian populations. II. The balance of forces between linkage and random assortment.

    Science.gov (United States)

    Wills, C; Miller, C

    1976-02-01

    It is shown, through theory and computer simulations of outbreeding Mendelian populations, that there may be conditions under which a balance is struck between two facotrs. The first is the advantage of random assortment, which will, when multilocus selection is for intermediate equilibrium values, lead to higher average heterozygosity than when linkage is introduced. There is some indication that random assortment is also advantageous when selection is toward a uniform distribution of equilibrium values. The second factor is the advantage of linkage between loci having positive epistatic interactions. When multilocus selection is for a bimodal distribution of equilibrium values an early advantage of random assortment is replaced by a later disadvantage. Linkage disequilibrium, which in finite populations is increased only by random or selective sampling, may hinder the movement of alleles to their selective equilibria, thus leading to the advantage of random assortment.-Some consequences of this approach to the structure of natural populations are discussed.

  19. Human umbilical cord hyaluronate. Neutral sugar content and carbohydrate-protein linkage studies.

    Science.gov (United States)

    Varma, R; Varma, R S; Allen, W S; Wardi, A H

    1975-07-14

    Paper chromatography of neutral sugars and gas chromatography of their aldononitrile acetates indicated the presence of fucose, arabinose and a small amount of glucose in purified human umbilical cord hyaluronate. The molar ratios of serine, threonine and aspartic acid to neutral sugars were not unity, suggesting the non-involvement of the neutral sugars and the amino acids in a carbohydrate-protein linkage. The same was indicated by an increase in the percentage of the aforementioned amino acids and by the absence of sugar alditols in umbilical cord hyaluronate reduced eith NaBH4 -PdCl2, after alkali treatment. This reduction caused a decrease in the intrinsic viscosity and molecular wieght to about one-half and an appreciable decrease in the specific rota tion of hyaluronate, suggesting a separation of the two antiparallel chains o the double helical hyaluronate. The umbilical cord hyluronate containe contained bound silicon and it is possible that this bound silicon may cross-link the two chains at interspersed intervals through the uronic acid moiety and/or through neutral sugars.

  20. Studying Hospitalizations and Mortality in the Netherlands: Feasible and Valid Using Two-Step Medical Record Linkage with Nationwide Registers.

    Directory of Open Access Journals (Sweden)

    Elske Sieswerda

    Full Text Available In the Netherlands, the postal code is needed to study hospitalizations of individuals in the nationwide hospitalization register. Studying hospitalizations longitudinally becomes troublesome if individuals change address. We aimed to report on the feasibility and validity of a two-step medical record linkage approach to examine longitudinal trends in hospitalizations and mortality in a study cohort. First, we linked a study cohort of 1564 survivors of childhood cancer with the Municipal Personal Records Database (GBA which has postal code history and mortality data available. Within GBA, we sampled a reference population matched on year of birth, gender and calendar year. Second, we extracted hospitalizations from the Hospital Discharge Register (LMR with a date of discharge during unique follow-up (based on date of birth, gender and postal code in GBA. We calculated the agreement of death and being hospitalized in survivors according to the registers and to available cohort data. We retrieved 1477 (94% survivors from GBA. Median percentages of unique/potential follow-up were 87% (survivors and 83% (reference persons. Characteristics of survivors and reference persons contributing to unique follow-up were comparable. Agreement of hospitalization during unique follow-up was 94% and agreement of death was 98%. In absence of unique identifiers in the Dutch hospitalization register, it is feasible and valid to study hospitalizations and mortality of individuals longitudinally using a two-step medical record linkage approach. Cohort studies in the Netherlands have the opportunity to study mortality and hospitalization rates over time. These outcomes provide insight into the burden of clinical events and healthcare use in studies on patients at risk of long-term morbidities.

  1. Studying Hospitalizations and Mortality in the Netherlands: Feasible and Valid Using Two-Step Medical Record Linkage with Nationwide Registers.

    Science.gov (United States)

    Sieswerda, Elske; Font-Gonzalez, Anna; Dijkgraaf, Marcel G W; Geskus, Ronald B; Heinen, Richard C; van der Pal, Helena J; van Leeuwen, Flora E; Caron, Huib N; Kremer, Leontien C; Reitsma, Johannes B

    2015-01-01

    In the Netherlands, the postal code is needed to study hospitalizations of individuals in the nationwide hospitalization register. Studying hospitalizations longitudinally becomes troublesome if individuals change address. We aimed to report on the feasibility and validity of a two-step medical record linkage approach to examine longitudinal trends in hospitalizations and mortality in a study cohort. First, we linked a study cohort of 1564 survivors of childhood cancer with the Municipal Personal Records Database (GBA) which has postal code history and mortality data available. Within GBA, we sampled a reference population matched on year of birth, gender and calendar year. Second, we extracted hospitalizations from the Hospital Discharge Register (LMR) with a date of discharge during unique follow-up (based on date of birth, gender and postal code in GBA). We calculated the agreement of death and being hospitalized in survivors according to the registers and to available cohort data. We retrieved 1477 (94%) survivors from GBA. Median percentages of unique/potential follow-up were 87% (survivors) and 83% (reference persons). Characteristics of survivors and reference persons contributing to unique follow-up were comparable. Agreement of hospitalization during unique follow-up was 94% and agreement of death was 98%. In absence of unique identifiers in the Dutch hospitalization register, it is feasible and valid to study hospitalizations and mortality of individuals longitudinally using a two-step medical record linkage approach. Cohort studies in the Netherlands have the opportunity to study mortality and hospitalization rates over time. These outcomes provide insight into the burden of clinical events and healthcare use in studies on patients at risk of long-term morbidities.

  2. Power assessment for genetic association study of human longevity using offspring of long-lived subjects

    DEFF Research Database (Denmark)

    Tan, Qihua; Zhao, Jing Hua; Li, Shuxia

    2010-01-01

    Recently, an indirect genetic association approach that compares genotype frequencies in offspring of long-lived subjects and offspring from random families has been introduced to study gene-longevity associations. Although the indirect genetic association has certain advantages over the direct...... association approach that compares genotype frequency between centenarians and young controls, the power has been of concern. This paper reports a power study performed on the indirect approach using computer simulation. We perform our simulation study by introducing the current Danish population life table...... and the proportional hazard model for generating individual lifespan. Family genotype data is generated using a genetic linkage program for given SNP allele frequency. Power is estimated by setting the type I error rate at 0.05 and by calculating the Armitage's chi-squared test statistic for 200 replicate samples...

  3. 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.

  4. 利用重组自交系群体构建番茄AFLP遗传连锁图谱%Construction AFLP Genetic Linkage Map of Tomato Using Recombinant Inbred Lines (RILs) Population

    Institute of Scientific and Technical Information of China (English)

    陈丽静; 王利; 王玉坤; 陶承光; 李君明; 王晓武; 李天来

    2012-01-01

    using the program JoinMap version 3.0. With 22 primer pairs, a total of 247 parental polymorphic bands were detected and 125 used for mapping, the total map length was 662 cM, consisted of 18 linkage groups, number of markers in the linkage groups varied from 3 to 22, the length of linkage groups were from 14.0 cM to 58.0 cM and mean marker interval distance from 2.27 cM to 13.3 cM individually, and a mean marker interval distance of 5.3 cM between markers. The map developed in the present study could be used for genetic mapping and molecular marker assisted breeding and quantitative trait locus mapping of tomato.

  5. Consumer segmentation and time interval between types of hospital admission: a clinical linkage database study.

    Science.gov (United States)

    Kadam, Umesh T; Lawson, Claire A; Moody, Dawn K; Teece, Lucy; Uttley, John; Harvey, John; Iqbal, Z; Jones, P W

    2017-03-14

    Healthcare policies target unplanned hospital admissions and 30-day re-admission as key measures of efficiency, but do not focus on factors that influence trajectories of different types of admissions in the same patient over time. To investigate the influence of consumer segmentation and patient factors on the time intervals between different types of hospital admission. A cohort design was applied to an anonymised linkage database for adults aged 40 years and over (N = 58 857). Measures included Mosaic segmentation, multimorbidity defined on six chronic condition registers and hospital admissions over a 27-month time period. The shortest mean time intervals between two consecutive planned admissions were: 90 years and over (160 days (95% confidence interval (CI): 146-175)), Mosaic groups 'Twilight subsistence' (171 days (164-179)) or 'Welfare borderline' and 'Municipal dependency' (177 days (172-182)) compared to the reference Mosaic groups (186 days (180-193)), and multimorbidity count of four or more (137 days (130-145)). Mosaic group 'Twilight subsistence' (rate ratio (RR) 1.22 (95% CI: 1.08-1.36)) or 'Welfare borderline' and 'Municipal dependency' RR 1.20 (1.10-1.31) were significantly associated with higher rate to an unplanned admission following a planned event. However, associations between patient factors and unplanned admissions were diminished by adjustment for planned admissions. Specific consumer segmentation and patient factors were associated with shorter time intervals between different types of admissions. The findings support innovation in public health approaches to prevent by a focus on long-term trajectories of hospital admissions, which include planned activity.

  6. Genetic aspects and genetic epidemiology of parasomnias.

    Science.gov (United States)

    Hublin, Christer; Kaprio, Jaakko

    2003-10-01

    Parasomnias are undesirable phenomena associated with sleep. Many of them run in families, and genetic factors have been long suggested to be involved in their occurrence. This article reviews the present knowledge of the genetics of the major classical behavioral parasomnias as well as present results from genetic epidemiological studies. The level and type of evidence for genetic effects varies much from parasomnia to parasomnia. The genetic factors are best established in enuresis, with several linkages to chromosomal loci, but their functions are not so far known. Environmental causes and gene-environment interactions are most probably also of great importance in the origin of complex traits or disorders such as parasomnias.

  7. Genome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand.

    Science.gov (United States)

    Phasukkijwatana, Nopasak; Kunhapan, Bussaraporn; Stankovich, Jim; Chuenkongkaew, Wanicha L; Thomson, Russell; Thornton, Timothy; Bahlo, Melanie; Mushiroda, Taisei; Nakamura, Yusuke; Mahasirimongkol, Surakameth; Tun, Aung Win; Srisawat, Chatchawan; Limwongse, Chanin; Peerapittayamongkol, Chayanon; Sura, Thanyachai; Suthammarak, Wichit; Lertrit, Patcharee

    2010-07-01

    Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P 2 in 10 of 16 allele sharing models tested) was then expanded to include the region 3q26.2-3q28 covering SLC7A14 (3q26.2), MFN1 (3q26.32), MRPL47 (3q26.33), MCCC1 (3q27.1), PARL (3q27.1) and OPA1 (3q28-q29). All of these candidate genes were selected from the Maestro database and had known to be localized in mitochondria. Sixty tag SNPs were genotyped in 86 cases, 211 of their relatives and 32 unrelated Thai controls, by multiplex-PCR-based Invader assay. Analyses using a powerful association testing tool that adjusts for relatedness (the M(QLS) statistic) showed the most evidence of association between two SNPs, rs3749446 and rs1402000 (located in PARL presenilins-associated rhomboid-like) and LHON expression (both P = 8.8 x 10(-5)). The mitochondrial PARL protease has been recently known to play a role with a dynamin-related OPA1 protein in preventing apoptotic events by slowing down the release of cytochrome c out of mitochondrial cristae junctions. Moreover, PARL is required to activate the intramembranous proteolyses resulting in the degradation of an accumulated pro-apoptotic protein in the outer mitochondrial membrane. Under these circumstances, variants of PARL are suggested to influence cell death by apoptosis which has long been believed to intrigue the neurodegeneration of LHON.

  8. Construction of an intra-specific sweet cherry (Prunus avium L.) genetic linkage map and synteny analysis with the Prunus reference map

    Science.gov (United States)

    Linkage maps of the sweet cherry cultivar ‘Emperor Francis’ (EF) and the wild forest cherry ‘New York 54’ (NY) were constructed using primarily simple sequence repeat (SSR) markers and gene-derived markers with known positions on the Prunus reference map. The success rate for identifying SSR markers...

  9. Conversion of chromosome-specific RAPDs into SCAR-based anchor markers for onion linkage maps and its application to genetic analyses inother Allium species

    NARCIS (Netherlands)

    Masuzaki, S.; Miyazaki, T.; McCallum, J.; Heusden, van A.W.; Kik, C.; Yamashita, K.; Tashiro, Y.

    2008-01-01

    Integration of previously developed Allium cepa linkage maps requires the availability of anchor markers for each of the eight chromosomes of shallot (A. cepa L. common group Aggregatum). To this end, eight RAPD markers originating from our previous research were converted into SCAR markers via clon

  10. Characterization of new microsatellite loci for population genetic studies in the Smooth Cauliflower Coral (Stylophora sp.)

    KAUST Repository

    Banguera-Hinestroza, E.

    2013-01-09

    A total of one hundred microsatellites loci were selected from the draft genome of Stylophora pistillata and evaluated in previously characterized samples of Stylophora cf pistillata from the Red Sea. 17 loci were amplified successfully and tested in 24 individuals from samples belonging to a single population from the central region of the Red Sea. The number of alleles ranged from 3 to 15 alleles per locus, while observed heterozygosity ranged from 0. 292 to 0. 95. Six of these loci showed significant deviations from Hardy-Weinberg equilibrium (HWE) expectations, and 4/136 paired loci comparisons suggested linkage disequilibrium after Bonferroni corrections. After excluding loci with significant HWE deviation and evidence of null alleles, average genetic diversity over loci in the population studied (N = 24, Nloci = 11) was 0. 701 ± 0. 380. This indicates that these loci can be used effectively to evaluate genetic diversity and undertake population genetics studies in Stylophora sp. populations. 2013 The Author(s).

  11. Construction of a Genetic Linkage Map and Identification of QTLs for Seed Weight and Seed Size Traits in Lentil (Lens culinaris Medik..

    Directory of Open Access Journals (Sweden)

    Priyanka Verma

    Full Text Available Seed weight and seed size both are quantitative traits and have been considered as important components of grain yield, thus identification of quantitative trait loci (QTL for seed traits in lentil (Lens culinaris would be beneficial for the improvement of grain yield. Hence the main objective of this study was to identify QTLs for seed traits using an intraspecific mapping population derived from a cross between L. culinaris cv. Precoz (seed weight-5.1g, seed size-5.7mm and L. culinaris cv. L830 (seed weight-2.2g, seed size-4mm comprising 126 F8-RILs. For this, two microsatellite genomic libraries enriched for (GA/CT and (GAA/CTT motif were constructed which resulted in the development of 501 new genomic SSR markers. Six hundred forty seven SSR markers (including 146 previously published were screened for parental polymorphism and 219 (33.8% were found to be polymorphic among the parents. Of these 216 were mapped on seven linkage groups at LOD4.0 spanning 1183.7cM with an average marker density of 5.48cM. Phenotypic data from the RILs was used to identify QTLs for the seed weight and seed size traits by single marker analysis (SMA followed by composite interval mapping (CIM which resulted in one QTL each for the 2 traits (qSW and qSS that were co-localized on LG4 and explained 48.4% and 27.5% of phenotypic variance respectively. The current study would serve as a strong foundation for further validation and fine mapping for utilization in lentil breeding programs.

  12. 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

  13. VT Wildlife Linkage Habitat

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The Wildlife Linkage Habitat Analysis uses landscape scale data to identify or predict the location of potentially significant wildlife linkage...

  14. 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.

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

    Science.gov (United States)

    2013-01-01

    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. PMID:23324215

  16. Linkages between ocean circulation, heat uptake and transient warming: a sensitivity study

    Science.gov (United States)

    Pfister, Patrik; Stocker, Thomas

    2016-04-01

    Transient global warming due to greenhouse gas radiative forcing is substantially reduced by ocean heat uptake (OHU). However, the fraction of equilibrium warming that is realized in transient climate model simulations differs strongly between models (Frölicher and Paynter 2015). It has been shown that this difference is not only related to the magnitude of OHU, but also to the radiative response the OHU causes, measured by the OHU efficacy (Winton et al., 2010). This efficacy is strongly influenced by the spatial pattern of the OHU and its changes (Rose et al. 2014, Winton et al. 2013), predominantly caused by changes in the Atlantic meridional overturning circulation (AMOC). Even in absence of external greenhouse gas forcing, an AMOC weakening causes a radiative imbalance at the top of the atmosphere (Peltier and Vettoretti, 2014), inducing in a net warming of the Earth System. We investigate linkages between those findings by performing both freshwater and greenhouse gas experiments in an Earth System Model of Intermediate Complexity. To assess the sensitivity of the results to ocean and atmospheric transport as well as climate sensitivity, we use an ensemble of model versions, systematically varying key parameters. We analyze circulation changes and radiative adjustments in conjunction with traditional warming metrics such as the transient climate response and the equilibrium climate sensitivity. This aims to improve the understanding of the influence of ocean circulation and OHU on transient climate change, and of the relevance of different metrics for describing this influence. References: Frölicher, T. L. and D.J. Paynter (2015), Extending the relationship between global warming and cumulative carbon emissions to multi-millennial timescales, Environ. Res. Lett., 10, 075022 Peltier, W. R., and G. Vettoretti (2014), Dansgaard-Oeschger oscillations predicted in a comprehensive model of glacial climate: A "kicked" salt oscillator in the Atlantic, Geophys. Res

  17. 西瓜遗传图谱构建及果实相关性状QTL分析%Construction of a Genetic Linkage Map and QTL Analysis of Fruit-Associated Traits in Watermelon

    Institute of Scientific and Technical Information of China (English)

    刘传奇; 高鹏; 栾非时

    2014-01-01

    ,覆盖基因组1484.3cM,平均图距15.46cM。利用QTLNetwork2.0分析,检测到6个西瓜果实相关性状的8个QTL位点和1对上位效应位点,其中包括果形指数QFSI1、中心可溶性固形物QCBR、中心果肉硬度QCFF、边缘果肉硬度QEFF、种子长度QSL各1个,种子宽度QSWD1、QSWD2、QSWD33个;上位效应位点包括果形指数FSI2、FSI3。表型贡献率大于等于10%的QTL有6个,可解释11.7%-18.8%的遗传变异。以CAPS标记为主要标记构建西瓜遗传图谱,并且定位了控制西瓜果实相关性状的8个加性QTL与1对上位性QTL,可用于进一步精细定位与克隆西瓜果实优良性状基因。%[Objective]The purpose of this study is to construct a molecular genetic map and map the QTL of the fruit-associated traits with CAPS and SSR markers in watermelon, which will provide a theoretical basis for traits improving, gene fine mapping and gene cloning.[Method]Fruits of female parent PI186490, male parent LSW-177 and F2 population derived from the cross between the two watermelon strains were picked in 40 days after pollination. Fruit shape index, center and edge brix, center and edge flesh firmness, rind hardness, seed length, seed width, seed thickness and 100-seed-weight were investigated correspondingly, then the obtained data were analyzed by SPSS19. Both parent materials genomes were resequenced by Illumina HiSeq 2000 platform for high-throughput sequencing, outputed 10G each data sample, covered more than 20× of watermelon genome. With the published genome as a reference, the obtained data were assembled with bwa, and explored for the SNP by Samtools. The sequence 1 000 bp around the SNP loci was extracted by self perl script and then inputed into SNP2CAPS to transform into CAPS markers. Twenty CAPS restriction sites were selected evenly on the 11 chromosomes. CAPS primers were designed 100-500bp around the mutation by Primer Premier 5 for PCR amplification and digestion detection. 1% agarose gel

  18. Analysis of four studies in a comparative framework reveals: health linkage consent rates on British cohort studies higher than on UK household panel surveys.

    Science.gov (United States)

    Knies, Gundi; Burton, Jonathan

    2014-11-27

    A number of cohort studies and longitudinal household panel studies in Great Britain have asked for consent to link survey data to administrative health data. We explore commonalities and differences in the process of collecting consent, achieved consent rates and biases in consent with respect to socio-demographic, socio-economic and health characteristics. We hypothesise that British cohort studies which are rooted within the health sciences achieve higher consent rates than the UK household longitudinal studies which are rooted within the social sciences. By contrast, the lack of a specific health focus in household panel studies means there may be less selectivity in consent, in particular, with respect to health characteristics. Survey designs and protocols for collecting informed consent to health record linkage on two British cohort studies and two UK household panel studies are systematically compared. Multivariate statistical analysis is then performed on information from one cohort and two household panel studies that share a great deal of the data linkage protocol but vary according to study branding, survey design and study population. We find that consent is higher in the British cohort studies than in the UK household panel studies, and is higher the more health-focused the study is. There are no systematic patterns of consent bias across the studies and where effects exist within a study or study type they tend to be small. Minority ethnic groups will be underrepresented in record linkage studies on the basis of all three studies. Systematic analysis of three studies in a comparative framework suggests that the factors associated with consent are idiosyncratic to the study. Analysis of linked health data is needed to establish whether selectivity in consent means the resulting research databases suffer from any biases that ought to be considered.

  19. 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.

  20. 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.

  1. Genetic diversity study on 12 X-STR loci of investigator® Argus X STR kit in Bangladeshi population.

    Science.gov (United States)

    Sufian, Abu; Hosen, Md Ismail; Fatema, Kaniz; Hossain, Tania; Hasan, Md Mahamud; Mazumder, Ashish Kumar; Akhteruzzaman, Sharif

    2016-12-08

    The X-chromosome short tandem repeat (STR) loci are of particular interest for solving complex kinship and paternity cases. Here, we report the genetic data from 209 unrelated Bangladeshi individuals (102 males and 107 females) that were genotyped using the 12 X-chromosomal STR markers included in the Investigator® Argus X-12 kit (Qiagen). The 12 X-STR markers are located in four linkage groups (linkage group I: DXS10135, DXS10148, and DXS8378; linkage group II: DXS7132, DXS10079, and DXS10074; linkage group III: DXS10103, HPRTB, and DXS10101; and linkage group IV: DXS10146, DXS10134, and DXS7423). Allelic frequencies of the 12 X-STR loci and haplotype frequencies of the four linkage groups were investigated. No significant difference was observed in the allele frequencies of males and females. Distributions of heterozygosity were observed from 64.5 to 92.5% among the studied 12 X STR loci. DXS10135 and DXS10101 loci were found to be most polymorphic. For all the four linkage groups, the haplotype diversity was found to be greater than 0.986. A total of 95, 73, 66, and 74 haplotypes were observed in linkage groups I, II, III, and IV, respectively. Hardy-Weinberg equilibrium tests showed no significant deviation from expected values for all 12 loci (p > 0.05). The exact test for pairwise linkage disequilibrium for the 12 loci in the male samples did not show any significant linkage disequilibrium except the DXS10103 and DXS10101 loci after the p values were corrected by Bonferroni's correction for multiple testing (p > 0.05/66). A combined power of discrimination in male and female individuals were 0.999999998159791 and 0.999999999999993, respectively. The combined mean exclusion chance were 0.999997635 in deficiency cases, 0.999999996 in normal trio cases, and 0.999999178 in duo cases. The currently investigated Bangladeshi population showed significant differences when compared with previously reported X-STR data from other 12 populations. The results of the

  2. Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects.

    Science.gov (United States)

    Dastani, Zari; Pajukanta, Päivi; Marcil, Michel; Rudzicz, Nicholas; Ruel, Isabelle; Bailey, Swneke D; Lee, Jenny C; Lemire, Mathieu; Faith, Janet; Platko, Jill; Rioux, John; Hudson, Thomas J; Gaudet, Daniel; Engert, James C; Genest, Jacques

    2010-03-01

    Low levels of high-density lipoprotein cholesterol (HDL-C) are an independent risk factor for cardiovascular disease. To identify novel genetic variants that contribute to HDL-C, we performed genome-wide scans and quantitative association studies in two study samples: a Quebec-wide study consisting of 11 multigenerational families and a study of 61 families from the Saguenay-Lac St-Jean (SLSJ) region of Quebec. The heritability of HDL-C in these study samples was 0.73 and 0.49, respectively. Variance components linkage methods identified a LOD score of 2.61 at 98 cM near the marker D16S515 in Quebec-wide families and an LOD score of 2.96 at 86 cM near the marker D16S2624 in SLSJ families. In the Quebec-wide sample, four families showed segregation over a 25.5-cM (18 Mb) region, which was further reduced to 6.6 Mb with additional markers. The coding regions of all genes within this region were sequenced. A missense variant in CHST6 segregated in four families and, with additional families, we observed a P value of 0.015 for this variant. However, an association study of this single-nucleotide polymorphism (SNP) in unrelated Quebec-wide samples was not significant. We also identified an SNP (rs11646677) in the same region, which was significantly associated with a low HDL-C (P=0.016) in the SLSJ study sample. In addition, RT-PCR results from cultured cells showed a significant difference in the expression of CHST6 and KIAA1576, another gene in the region. Our data constitute additional evidence for a locus on chromosome 16q23-24 that affects HDL-C levels in two independent French-Canadian studies.

  3. PLAB and UK graduates' performance on MRCP(UK) and MRCGP examinations: data linkage study.

    Science.gov (United States)

    McManus, I C; Wakeford, Richard

    2014-04-17

    To assess whether international medical graduates passing the two examinations set by the Professional and Linguistic Assessments Board (PLAB1 and PLAB2) of the General Medical Council (GMC) are equivalent to UK graduates at the end of the first foundation year of medical training (F1), as the GMC requires, and if not, to assess what changes in the PLAB pass marks might produce equivalence. Data linkage of GMC PLAB performance data with data from the Royal Colleges of Physicians and the Royal College of General Practitioners on performance of PLAB graduates and UK graduates at the MRCP(UK) and MRCGP examinations. Doctors in training for internal medicine or general practice in the United Kingdom. 7829, 5135, and 4387 PLAB graduates on their first attempt at MRCP(UK) Part 1, Part 2, and PACES assessments from 2001 to 2012 compared with 18,532, 14,094, and 14,376 UK graduates taking the same assessments; 3160 PLAB1 graduates making their first attempt at the MRCGP AKT during 2007-12 compared with 14,235 UK graduates; and 1411 PLAB2 graduates making their first attempt at the MRCGP CSA during 2010-12 compared with 6935 UK graduates. Performance at MRCP(UK) Part 1, Part 2, and PACES assessments, and MRCGP AKT and CSA assessments in relation to performance on PLAB1 and PLAB2 assessments, as well as to International English Language Testing System (IELTS) scores. MRCP(UK), MRCGP, and PLAB results were analysed as marks relative to the pass mark at the first attempt. PLAB1 marks were a valid predictor of MRCP(UK) Part 1, MRCP(UK) Part 2, and MRCGP AKT (r=0.521, 0.390, and 0.490; all PUK) PACES and MRCGP CSA (r=0.274, 0.321; both PUK) and MRCGP assessments (Glass's Δ=0.94, 0.91, 1.40, 1.01, and 1.82 for MRCP(UK) Part 1, Part 2, and PACES and MRCGP AKT and CSA), and were more likely to fail assessments and to progress more slowly than UK medical graduates. IELTS scores correlated significantly with later performance, multiple regression showing that the effect of PLAB1 (

  4. PLAB and UK graduates’ performance on MRCP(UK) and MRCGP examinations: data linkage study

    Science.gov (United States)

    Wakeford, Richard

    2014-01-01

    Objectives To assess whether international medical graduates passing the two examinations set by the Professional and Linguistic Assessments Board (PLAB1 and PLAB2) of the General Medical Council (GMC) are equivalent to UK graduates at the end of the first foundation year of medical training (F1), as the GMC requires, and if not, to assess what changes in the PLAB pass marks might produce equivalence. Design Data linkage of GMC PLAB performance data with data from the Royal Colleges of Physicians and the Royal College of General Practitioners on performance of PLAB graduates and UK graduates at the MRCP(UK) and MRCGP examinations. Setting Doctors in training for internal medicine or general practice in the United Kingdom. Participants 7829, 5135, and 4387 PLAB graduates on their first attempt at MRCP(UK) Part 1, Part 2, and PACES assessments from 2001 to 2012 compared with 18 532, 14 094, and 14 376 UK graduates taking the same assessments; 3160 PLAB1 graduates making their first attempt at the MRCGP AKT during 2007-12 compared with 14 235 UK graduates; and 1411 PLAB2 graduates making their first attempt at the MRCGP CSA during 2010-12 compared with 6935 UK graduates. Main outcome measures Performance at MRCP(UK) Part 1, Part 2, and PACES assessments, and MRCGP AKT and CSA assessments in relation to performance on PLAB1 and PLAB2 assessments, as well as to International English Language Testing System (IELTS) scores. MRCP(UK), MRCGP, and PLAB results were analysed as marks relative to the pass mark at the first attempt. Results PLAB1 marks were a valid predictor of MRCP(UK) Part 1, MRCP(UK) Part 2, and MRCGP AKT (r=0.521, 0.390, and 0.490; all PIELTS scores correlated significantly with later performance, multiple regression showing that the effect of PLAB1 (β=0.496) was much stronger than the effect of IELTS (β=0.086). Changes to PLAB pass marks that would result in international medical graduate and UK medical graduate equivalence were assessed in two

  5. Robust physical methods that enrich genomic regions identical by descent for linkage studies: confirmation of a locus for osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Cohen Nadine

    2009-03-01

    Full Text Available Abstract Background The monogenic disease osteogenesis imperfecta (OI is due to single mutations in either of the collagen genes ColA1 or ColA2, but within the same family a given mutation is accompanied by a wide range of disease severity. Although this phenotypic variability implies the existence of modifier gene variants, genome wide scanning of DNA from OI patients has not been reported. Promising genome wide marker-independent physical methods for identifying disease-related loci have lacked robustness for widespread applicability. Therefore we sought to improve these methods and demonstrate their performance to identify known and novel loci relevant to OI. Results We have improved methods for enriching regions of identity-by-descent (IBD shared between related, afflicted individuals. The extent of enrichment exceeds 10- to 50-fold for some loci. The efficiency of the new process is shown by confirmation of the identification of the Col1A2 locus in osteogenesis imperfecta patients from Amish families. Moreover the analysis revealed additional candidate linkage loci that may harbour modifier genes for OI; a locus on chromosome 1q includes COX-2, a gene implicated in osteogenesis. Conclusion Technology for physical enrichment of IBD loci is now robust and applicable for finding genes for monogenic diseases and genes for complex diseases. The data support the further investigation of genetic loci other than collagen gene loci to identify genes affecting the clinical expression of osteogenesis imperfecta. The discrimination of IBD mapping will be enhanced when the IBD enrichment procedure is coupled with deep resequencing.

  6. Linkage analysis of quantitative trait loci in the presence of heterogeneity.

    Science.gov (United States)

    Ekstrøm, Claus Thorn; Dalgaard, Peter

    2003-01-01

    Variance component modeling for linkage analysis of quantitative traits is a powerful tool for detecting and locating genes affecting a trait of interest, but the presence of genetic heterogeneity will decrease the power of a linkage study and may even give biased estimates of the location of the quantitative trait loci. Many complex diseases are believed to be influenced by multiple genes and therefore genetic heterogeneity is likely to be present for many real applications of linkage analysis. We consider a mixture of multivariate normals to model locus heterogeneity by allowing only a proportion of the sampled pedigrees to segregate trait-influencing allele(s) at a specific locus. However, for mixtures of normals the classical asymptotic distribution theory of the maximum likelihood estimates does not hold, so tests of linkage and/or heterogeneity are evaluated using resampling methods. It is shown that allowing for genetic heterogeneity leads to an increase in power to detect linkage. This increase is more prominent when the genetic effect of the locus is small or when the percentage of pedigrees not segregating trait-influencing allele(s) at the locus is high.

  7. [Genetics in the study of HIV infection].

    Science.gov (United States)

    Amoroso, Antonio; Savoldi, Silvana

    2012-01-01

    Thirty years after the discovery of the human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS), no effective vaccines are available and there is no cure for the disease. The susceptibility to HIV infection shows a considerable degree of individual heterogeneity, which may be largely due to the genetic variability of the host. In an effort to find the host factors required for viral replication, to identify the crucial pathogenetic pathways, and reveal the full armament of host defenses, there has been a shift from candidate-gene studies to unbiased genomewide genetic and functional studies. Nevertheless, the number of established genetic factors involved in the susceptibility to diseases caused by HIV infection remains small, explaining only 15-20% of the observed heterogeneity, most of which is attributable to polymorphisms of human leukocyte antigens (HLA). Genetic studies, however, have allowed to clarify which genetic variations underlie the adverse response to some antiretroviral drugs (such as HLA-B*5701 in the treatment with abacavir) or the occurrence of renal complications as the disease progresses. The results of these studies already have a possible impact on healthcare practice.

  8. Candidate region linkage analysis in twins discordant or concordant for depression symptomatology

    DEFF Research Database (Denmark)

    Christiansen, Lene; Tan, Q; Kruse, T A

    2009-01-01

    Genetic risk factors contribute considerably to both clinical affective disorders and subsyndromal mood level. There is moreover evidence to suggest that the genetic basis of bipolar disorder and unipolar depression overlap to some extent, and several linkage analyses have suggested evidence...... for a common susceptibility locus in affective disorders on chromosome 12q24. In this study we investigated the chromosome 12 candidate region for linkage to the mean level of depression symptomatology, over a 10-year follow-up, using a highly informative sample of concordant and discordant twin pairs selected...

  9. Test site predicts HIV care linkage and antiretroviral therapy initiation: a prospective 3.5 year cohort study of HIV-positive testers in northern Tanzania

    OpenAIRE

    Reddy, Elizabeth A.; Agala, Chris Bernard; Maro, Venance P.; Ostermann, Jan; Pence, Brian W.; Itemba, Dafrosa K.; Safley, Donna; Yao, Jia; Thielman, Nathan M.; Whetten, Kathryn

    2016-01-01

    Background Linkage to HIV care is crucial to the success of antiretroviral therapy (ART) programs worldwide, loss to follow up at all stages of the care continuum is frequent, and long-term prospective studies of care linkage are currently lacking. Methods Consecutive clients who tested HIV-positive were enrolled from four HIV testing centers (1 health facility and 3 community-based centers) in the Kilimanjaro region of Tanzania as part of the larger Coping with HIV/AIDS in Tanzania (CHAT) pr...

  10. Genetic homogeneity in Sjoegren-Larsson syndrome: Linkage to chromosome 17p in families of different non-Swedish ethnic origins

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, G.R.; Lee, M.; Compton, J.G. [and others

    1995-11-01

    Sjoegren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. Three United States families, three Egyptian families, and one Israeli Arab family were investigated for linkage of the SLS gene to a region of chromosome 17. Pairwise and multipoint linkage analysis with nine markers mapped the SLS gene to the same region of the genome as that reported in Swedish SLS pedigrees. Examination of recombinants by haplotype analysis showed that the gene lies in the region containing the markers D17S953, D17S805, D17S689, and D17S842. D17S805 is pericentromeric on 17p. Patients in two consanguineous Egyptian families were homozygous at the nine marker loci tested, and another patient from a third family was homozygous for eight of the nine, suggesting that within each of these families the region of chromosome 17 carrying the SLS gene is identical by descent. Linkage of the SLS gene to chromosome 17p in families of Arabic, mixed European, Native American, and Swedish descent provides evidence for a single SLS locus and should prove useful for diagnosis and carrier detection in worldwide cases. 25 refs., 4 figs., 1 tab.

  11. Molecular Genetic Diagnostics of Prader-Willi Syndrome: a Validation of Linkage Analysis for the Chinese Population%普拉德-威利综合征的分子遗传诊断:一种连锁分析方法的初步建立

    Institute of Scientific and Technical Information of China (English)

    李洪义; 孟舒; 陈争; 李海飞; 杜敏联; 马华梅; 魏海云; 段红蕾; 郑辉; 闻人庆; 宋新明

    2007-01-01

    普拉德-威利综合征(Prader-Willi Syndrome,PWS)是一种基因组印记相关的疾病,是引起肥胖最常见的遗传综合征.分子和细胞遗传学检查对于该病早期诊断非常重要.通过选择PWS典型缺失区域内、外的STR遗传标记,初步建立了一种适用于中国人群的PWS核心家庭连锁分析方法,并用该方法确定了一例缺失型和一例异源单亲二体型PWS患者,经甲基化特异性PCR和高分辨染色体核型分析验证上述结果正确.同时,该连锁分析方法可以具体区分PWS的分子发病类型,从而为PWS家庭的遗传咨询提供信息,并为进一步研究PWS基因型和表型的关系提供了可能.%Prader-Willi Syndrome (PWS) is a genetic disorder that is difficult to detect, particularly at an early age. PWS is caused by disruption of normal, epigenetically controlled gene function in the chromosome 15q11-q13 region. Clinical symptoms are difficult to diagnose in infants and only become clearer at later ages as the patients develop hyperphagia and morbid obesity. Molecular genetic tests are able to definitively diagnose PWS and allow early diagnosis of the syndrome. High resolution cytogenetic testing, methylation-specific PCR (MS-PCR), and linkage analysis are routinely used to diagnose PWS. To establish a linkage analysis method for Chinese patients, this study identified a useful set of STR markers in the typical PWS deletion and adjacent area, for linkage analysis in two Chinese families with PWS offspring. Using this method, the authors confirmed that one patient had a paternal deletion in chromosome 15q11-q13 and the other patient had maternal uniparental heterodisomy of chromosome 15. MS-PCR and high resolution chromosome G-banding also confirmed this diagnosis. This linkage analysis method can detect both deletion and uniparental disomy, thus providing valuable information for genetic counseling and the opportunity to analyze the relationship between the genotype and

  12. Genetic Mapping in Human Disease

    OpenAIRE

    Altshuler, David; Daly, Mark J; Lander, Eric S.

    2008-01-01

    Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases. We discuss the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome-wide association studies of common diseases, and discuss questions and challenges that lie ahead.

  13. The Generalized Higher Criticism for Testing SNP-Set Effects in Genetic Association Studies.

    Science.gov (United States)

    Barnett, Ian; Mukherjee, Rajarshi; Lin, Xihong

    2017-01-01

    It is of substantial interest to study the effects of genes, genetic pathways, and networks on the risk of complex diseases. These genetic constructs each contain multiple SNPs, which are often correlated and function jointly, and might be large in number. However, only a sparse subset of SNPs in a genetic construct is generally associated with the disease of interest. In this article, we propose the generalized higher criticism (GHC) to test for the association between an SNP set and a disease outcome. The higher criticism is a test traditionally used in high-dimensional signal detection settings when marginal test statistics are independent and the number of parameters is very large. However, these assumptions do not always hold in genetic association studies, due to linkage disequilibrium among SNPs and the finite number of SNPs in an SNP set in each genetic construct. The proposed GHC overcomes the limitations of the higher criticism by allowing for arbitrary correlation structures among the SNPs in an SNP-set, while performing accurate analytic p-value calculations for any finite number of SNPs in the SNP-set. We obtain the detection boundary of the GHC test. We compared empirically using simulations the power of the GHC method with existing SNP-set tests over a range of genetic regions with varied correlation structures and signal sparsity. We apply the proposed methods to analyze the CGEM breast cancer genome-wide association study. Supplementary materials for this article are available online.

  14. Molecular evaluation of genetic diversity and association studies in rice (Oryza sativa L.)

    Indian Academy of Sciences (India)

    C. Vanniarajan; K. K. Vinod; Andy Pereira

    2011-04-01

    In the present study, we tested rice genotypes that included un(der)exploited landraces of Tamil Nadu along with indica and japonica test cultivars to ascertain their genetic diversity structure. Highly polymorphic microsatellite markers were used for generating marker segregation data. A novel measure, allele discrimination index, was used to determine subpopulation differentiation power of each marker. Phenotypic data were collected for yield and component traits. Pattern of molecular differentiation separated indica and japonica genotypes; indica genotypes had two subpopulations within. Landraces were found to have indica genome, but formed a separate subgroup with low linkage disequilibrium. The landraces further separated into distinct group in both hierarchical clustering analysis using neighbour-joining method as well as in the model based population structure analysis. Japonica and the remaining indica cultivars formed two other distinct groups. Linkage disequilibrium observed in the whole population was considerably reduced in subpopulations. Low linkage disequilibrium of landforms suggests their narrow adaptation in local geographical niche. Many population specific alleles could be identified particularly for japonica cultivars and landraces. Association analysis revealed nine marker–trait associations with three agronomic traits, of which 67% were previously reported. Although the testing landraces together with known cultivars had permitted genomewide association mapping, the experiment offers scope to study more landraces collected from the entire geographical region for drawing more reliable information.

  15. The Ischemic Stroke Genetics Study (ISGS Protocol

    Directory of Open Access Journals (Sweden)

    Rich Stephen S

    2003-07-01

    Full Text Available Abstract Background The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. Methods/Design The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes β-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. Discussion The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes.

  16. Visualization of pairwise and multilocus linkage disequilibrium structure using latent forests.

    Directory of Open Access Journals (Sweden)

    Raphaël Mourad

    Full Text Available Linkage disequilibrium study represents a major issue in statistical genetics as it plays a fundamental role in gene mapping and helps us to learn more about human history. The linkage disequilibrium complex structure makes its exploratory data analysis essential yet challenging. Visualization methods, such as the triangular heat map implemented in Haploview, provide simple and useful tools to help understand complex genetic patterns, but remain insufficient to fully describe them. Probabilistic graphical models have been widely recognized as a powerful formalism allowing a concise and accurate modeling of dependences between variables. In this paper, we propose a method for short-range, long-range and chromosome-wide linkage disequilibrium visualization using forests of hierarchical latent class models. Thanks to its hierarchical nature, our method is shown to provide a compact view of both pairwise and multilocus linkage disequilibrium spatial structures for the geneticist. Besides, a multilocus linkage disequilibrium measure has been designed to evaluate linkage disequilibrium in hierarchy clusters. To learn the proposed model, a new scalable algorithm is presented. It constrains the dependence scope, relying on physical positions, and is able to deal with more than one hundred thousand single nucleotide polymorphisms. The proposed algorithm is fast and does not require phase genotypic data.

  17. Studying Extrachromosomal Genetic Elements in Sulfolobus

    DEFF Research Database (Denmark)

    Guannan, Liu

    facilitated the characterization of viruses, plasmids and membrane vesicles. Studying the interactions between Sulfolobus and extrachromosomal genetic elements has provided many new insights into basic molecular processes. Secreted membrane vesicle seems to be a common characteristic for Sulfolobus. In order...... of random chromosomal fragments, including IS elements. The results suggest that membrane vesicles could serve as vehicles for the inter-cellular transport of genetic material. A variant of ATV, ATV2, was isolated that infected a newly isolated Sulfolobus solfataricus P3 strain. Comparative genomics......, whereas the deactivation of pKEF9 in S. solfataricus was caused by mobile elements after it had integrated into the host genome....

  18. Studying Extrachromosomal Genetic Elements in Sulfolobus

    DEFF Research Database (Denmark)

    Guannan, Liu

    facilitated the characterization of viruses, plasmids and membrane vesicles. Studying the interactions between Sulfolobus and extrachromosomal genetic elements has provided many new insights into basic molecular processes. Secreted membrane vesicle seems to be a common characteristic for Sulfolobus. In order...... of random chromosomal fragments, including IS elements. The results suggest that membrane vesicles could serve as vehicles for the inter-cellular transport of genetic material. A variant of ATV, ATV2, was isolated that infected a newly isolated Sulfolobus solfataricus P3 strain. Comparative genomics......, whereas the deactivation of pKEF9 in S. solfataricus was caused by mobile elements after it had integrated into the host genome....

  19. GeneLink: a database to facilitate genetic studies of complex traits

    Directory of Open Access Journals (Sweden)

    Wolfsberg Tyra G

    2004-10-01

    Full Text Available Abstract Background In contrast to gene-mapping studies of simple Mendelian disorders, genetic analyses of complex traits are far more challenging, and high quality data management systems are often critical to the success of these projects. To minimize the difficulties inherent in complex trait studies, we have developed GeneLink, a Web-accessible, password-protected Sybase database. Results GeneLink is a powerful tool for complex trait mapping, enabling genotypic data to be easily merged with pedigree and extensive phenotypic data. Specifically designed to facilitate large-scale (multi-center genetic linkage or association studies, GeneLink securely and efficiently handles large amounts of data and provides additional features to facilitate data analysis by existing software packages and quality control. These include the ability to download chromosome-specific data files containing marker data in map order in various formats appropriate for downstream analyses (e.g., GAS and LINKAGE. Furthermore, an unlimited number of phenotypes (either qualitative or quantitative can be stored and analyzed. Finally, GeneLink generates several quality assurance reports, including genotyping success rates of specified DNA samples or success and heterozygosity rates for specified markers. Conclusions GeneLink has already proven an invaluable tool for complex trait mapping studies and is discussed primarily in the context of our large, multi-center study of hereditary prostate cancer (HPC. GeneLink is freely available at http://research.nhgri.nih.gov/genelink.

  20. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of the

  1. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of the

  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. From linkage studies to epigenetics: what we know and what we need to know in the neurobiology of schizophrenia.

    Directory of Open Access Journals (Sweden)

    Ariel eCariaga-Martinez

    2016-05-01

    Full Text Available Schizophrenia is a complex psychiatric disorder characterized by the presence of positive, negative and cognitive symptoms that lacks a unifying neuropathology. In the present paper, we will review the current understanding of molecular dysregulation in schizophrenia, including genetic and epigenetic studies. In relation to the latter, basic research suggests that normal cognition is regulated by epigenetic mechanisms and its dysfunction occurs upon epigenetic misregulation, providing new insights into missing heritability of complex psychiatric diseases, referring to the discrepancy between epidemiological heritability and the proportion of phenotypic variation explained by DNA sequence difference. In schizophrenia the absence of consistently replicated genetic effects together with evidence for lasting changes in gene expression after environmental exposures suggest a role of epigenetic mechanisms. In this review we will focus on epigenetic modifications as a key mechanism through which environmental factors interact with individual's genetic constitution to affect risk of psychotic conditions throughout life.

  4. 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.

  5. Directed Graphs, Decompositions, and Spatial Linkages

    CERN Document Server

    Shai, Offer; Whiteley, Walter

    2010-01-01

    The decomposition of a system of constraints into small basic components is an important tool of design and analysis. Specifically, the decomposition of a linkage into minimal components is a central tool of analysis and synthesis of linkages. In this paper we prove that every pinned 3-isostatic (minimally rigid) graph (grounded linkage) has a unique decomposition into minimal strongly connected components (in the sense of directed graphs) which we call 3-Assur graphs. This analysis extends the Assur decompositions of plane linkages previously studied in the mathematical and the mechanical engineering literature. These 3-Assur graphs are the central building blocks for all kinematic linkages in 3-space. They share a number of key combinatorial and geometric properties with the 2-Assur graphs, including an associated lower block-triangular decomposition of the pinned rigidity matrix which provides a format for extending the motion induced by inserting one driver in a bottom Assur linkage to the joints of the e...

  6. Detecting referral and selection bias by the anonymous linkage of practice, hospital and clinic data using Secure and Private Record Linkage (SAPREL: case study from the evaluation of the Improved Access to Psychological Therapy (IAPT service

    Directory of Open Access Journals (Sweden)

    Parry Glenys

    2011-10-01

    Full Text Available Abstract Background The evaluation of demonstration sites set up to provide improved access to psychological therapies (IAPT comprised the study of all people identified as having common mental health problems (CMHP, those referred to the IAPT service, and a sample of attenders studied in-depth. Information technology makes it feasible to link practice, hospital and IAPT clinic data to evaluate the representativeness of these samples. However, researchers do not have permission to browse and link these data without the patients' consent. Objective To demonstrate the use of a mixed deterministic-probabilistic method of secure and private record linkage (SAPREL - to describe selection bias in subjects chosen for in-depth evaluation. Method We extracted, pseudonymised and used fuzzy logic to link multiple health records without the researcher knowing the patient's identity. The method can be characterised as a three party protocol mainly using deterministic algorithms with dynamic linking strategies; though incorporating some elements of probabilistic linkage. Within the data providers' safe haven we extracted: Demographic data, hospital utilisation and IAPT clinic data; converted post code to index of multiple deprivation (IMD; and identified people with CMHP. We contrasted the age, gender, ethnicity and IMD for the in-depth evaluation sample with people referred to IAPT, use hospital services, and the population as a whole. Results The in IAPT-in-depth group had a mean age of 43.1 years; CI: 41.0 - 45.2 (n = 166; the IAPT-referred 40.2 years; CI: 39.4 - 40.9 (n = 1118; and those with CMHP 43.6 years SEM 0.15. (n = 12210. Whilst around 67% of those with a CMHP were women, compared to 70% of those referred to IAPT, and 75% of those subject to in-depth evaluation (Chi square p Conclusions The sample studied in-depth were older, more likely female, and less deprived than people with CMHP, and fewer had recorded ethnic minority status. Anonymous

  7. Detecting referral and selection bias by the anonymous linkage of practice, hospital and clinic data using Secure and Private Record Linkage (SAPREL): case study from the evaluation of the Improved Access to Psychological Therapy (IAPT) service

    Science.gov (United States)

    2011-01-01

    Background The evaluation of demonstration sites set up to provide improved access to psychological therapies (IAPT) comprised the study of all people identified as having common mental health problems (CMHP), those referred to the IAPT service, and a sample of attenders studied in-depth. Information technology makes it feasible to link practice, hospital and IAPT clinic data to evaluate the representativeness of these samples. However, researchers do not have permission to browse and link these data without the patients' consent. Objective To demonstrate the use of a mixed deterministic-probabilistic method of secure and private record linkage (SAPREL) - to describe selection bias in subjects chosen for in-depth evaluation. Method We extracted, pseudonymised and used fuzzy logic to link multiple health records without the researcher knowing the patient's identity. The method can be characterised as a three party protocol mainly using deterministic algorithms with dynamic linking strategies; though incorporating some elements of probabilistic linkage. Within the data providers' safe haven we extracted: Demographic data, hospital utilisation and IAPT clinic data; converted post code to index of multiple deprivation (IMD); and identified people with CMHP. We contrasted the age, gender, ethnicity and IMD for the in-depth evaluation sample with people referred to IAPT, use hospital services, and the population as a whole. Results The in IAPT-in-depth group had a mean age of 43.1 years; CI: 41.0 - 45.2 (n = 166); the IAPT-referred 40.2 years; CI: 39.4 - 40.9 (n = 1118); and those with CMHP 43.6 years SEM 0.15. (n = 12210). Whilst around 67% of those with a CMHP were women, compared to 70% of those referred to IAPT, and 75% of those subject to in-depth evaluation (Chi square p < 0.001). The mean IMD score for the in-depth evaluation group was 36.6; CI: 34.2 - 38.9; (n = 166); of those referred to IAPT 38.7; CI: 37.9 - 39.6; (n = 1117); and of people with CMHP 37.6; CI 37

  8. Power assessment for genetic association study of human longevity using offspring of long-lived subjects.

    Science.gov (United States)

    Tan, Qihua; Zhao, Jing Hua; Li, Shuxia; Kruse, Torben A; Christensen, Kaare

    2010-07-01

    Recently, an indirect genetic association approach that compares genotype frequencies in offspring of long-lived subjects and offspring from random families has been introduced to study gene-longevity associations. Although the indirect genetic association has certain advantages over the direct association approach that compares genotype frequency between centenarians and young controls, the power has been of concern. This paper reports a power study performed on the indirect approach using computer simulation. We perform our simulation study by introducing the current Danish population life table and the proportional hazard model for generating individual lifespan. Family genotype data is generated using a genetic linkage program for given SNP allele frequency. Power is estimated by setting the type I error rate at 0.05 and by calculating the Armitage's chi-squared test statistic for 200 replicate samples for each setting of the specified allele risk and frequency parameters under different modes of inheritance and for different sample sizes. The indirect genetic association analysis is a valid approach for studying gene-longevity association, but the sample size requirement is about 3-4 time larger than the direct approach. It also has low power in detecting non-additive effect genes. Indirect genetic association using offspring from families with both parents as nonagenarians is nearly as powerful as using offspring from families with one centenarian parent. In conclusion, the indirect design can be a good choice for studying longevity in comparison with other alternatives, when relatively large sample size is available.

  9. Experimental evolution, behavior and genetics: Associative learning as a case study

    Institute of Scientific and Technical Information of China (English)

    Elisabetta VERSACE

    2015-01-01

    The evolutionary dynamics of behavioral traits reflect phenotypic and genetic changes.Methodological difficulties in analyzing the genetic dynamics of complex traits have left open questions on the mechanisms that have shaped complex behaviors and cognitive abilities.A strategy to investigate the change of behavior across generations is to assume that genetic constraints have a negligible role in evolution (the phenotypic gambit) and focus on the phenotype as a proxy for genetic evolution.Empirical evidence and technologic advances in genomics question the choice of neglecting the genetic underlying the dynamics of behavioral evolution.I first discuss the relevance of genetic factors-e.g.genetic variability,genetic linkage,gene interactions -in shaping evolution,showing the importance of taking genetic factors into account when dealing with evolutionary dynamics.I subsequently describe the recent advancements in genetics and genomics that make the investigation of the ongoing evolutionary process of behavioral traits finally attainable.In particular,by applying genomic resequencing to experimental evolution-a method called Evolve & Resequence-it is possible to monitor at the same time phenotypic and genomic changes in populations exposed to controlled selective pressures.Experimental evolution of associative learning,a well-known trait that promptly responds to selection,is a convenient model to illustrate this approach applied to behavior and cognition.Taking into account the recent achievements of the field,I discuss how to design and conduct an effective Evolve & Resequence study on associative learning in Drosophila.By integrating phenotypic and genomic data in the investigation of evolutionary dynamics,new insights can be gained on longstanding questions such as the modularity of mind and its evolution [Current Zoology 61 (2):226-241,2015].

  10. Presymptomatic studies in genetic frontotemporal dementia.

    Science.gov (United States)

    Rohrer, J D; Warren, J D; Fox, N C; Rossor, M N

    2013-10-01

    Approximately 20% of patients with the neurodegenerative disorder frontotemporal dementia (FTD) have an autosomal dominant pattern of inheritance. Genetic FTD is caused by mutations in three genes in most cases (progranulin, microtubule-associated protein tau and chromosome 9 open reading frame 72) although a number of other genes are rare causes. Studies of other neurodegenerative diseases have shown imaging and biomarker evidence of disease onset many years prior to the development of symptoms. Similar studies in genetic FTD are now revealing evidence of a series of presymptomatic changes, initially in plasma biomarkers followed by MR imaging abnormalities of functional and structural connectivity and then grey matter atrophy. Lastly, neuropsychometric tests become abnormal in proximity to the onset of symptoms. Such studies have been relatively small until now but research centres with an expertise in genetic FTD are now forming consortia such as the Genetic Frontotemporal Dementia Initiative (GenFI) to create larger cohorts that can form the basis of future clinical trials. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. 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.

  12. Simulating a base population in honey bee for molecular genetic studies

    Directory of Open Access Journals (Sweden)

    Gupta Pooja

    2012-06-01

    Full Text Available Abstract Background Over the past years, reports have indicated that honey bee populations are declining and that infestation by an ecto-parasitic mite (Varroa destructor is one of the main causes. Selective breeding of resistant bees can help to prevent losses due to the parasite, but it requires that a robust breeding program and genetic evaluation are implemented. Genomic selection has emerged as an important tool in animal breeding programs and simulation studies have shown that it yields more accurate breeding value estimates, higher genetic gain and low rates of inbreeding. Since genomic selection relies on marker data, simulations conducted on a genomic dataset are a pre-requisite before selection can be implemented. Although genomic datasets have been simulated in other species undergoing genetic evaluation, simulation of a genomic dataset specific to the honey bee is required since this species has a distinct genetic and reproductive biology. Our software program was aimed at constructing a base population by simulating a random mating honey bee population. A forward-time population simulation approach was applied since it allows modeling of genetic characteristics and reproductive behavior specific to the honey bee. Results Our software program yielded a genomic dataset for a base population in linkage disequilibrium. In addition, information was obtained on (1 the position of markers on each chromosome, (2 allele frequency, (3 χ2 statistics for Hardy-Weinberg equilibrium, (4 a sorted list of markers with a minor allele frequency less than or equal to the input value, (5 average r2 values of linkage disequilibrium between all simulated marker loci pair for all generations and (6 average r2 value of linkage disequilibrium in the last generation for selected markers with the highest minor allele frequency. Conclusion We developed a software program that takes into account the genetic and reproductive biology specific to the honey bee

  13. The construction of genetic linkage frame map in tetraploid Medicago using RAPD markers%利用RAPD技术构建四倍体苜蓿遗传连锁图谱

    Institute of Scientific and Technical Information of China (English)

    刘曙娜; 于林清; 周延林; 吉仁花; 陈世茹; 孙娟娟; 么婷婷

    2012-01-01

    Using random amplified polymorphic DNA (RAPD) molecular genetic markers analyze the F2 population of 94 plant individuals. The F2 segregating population derived from a self-pollinated F1 hybrid individual of the cross Medicago sativa ×Medicago falcata. The genetic analyses were performed by using maximum-likelihood equations and related computer programs. The genetic map comprises 74 markers, and contains 8 linkage groups covering 1 261. 5 cM, with an average distance of 24. 73 cM between markers. This genetic linkage map provides an entry point for the construction of saturated tetraploid alfalfa molecular genetic map and further development of alfalfa molecular genetic research.%利用随机扩增DNA多态性分子遗传标记(RAPD)对F2群体进行分析.F2群体由F1群体(高产紫花苜蓿×高抗黄花苜蓿得到F1代)自交获得.应用MAPMAKER/EXP(3.0)与JionMap 4.0并结合MapDrawV 2.1软件构建四倍体苜蓿的遗传连锁图谱.从192个随机引物中筛选出72个引物,对94个F2个体及F1双亲DNA样本进行了RAPD扩增,共获得51个RAPD标记,构建了四倍体苜蓿分子遗传连锁框架图,其中包含8个连锁群,标记覆盖的基因组总长度约为1 261.5 cM,标记间平均距离为24.73 cM.本图谱为构建饱和的四倍体苜蓿分子遗传图谱提供了框架结构,为进一步开展苜蓿分子遗传方面的研究奠定了基础.

  14. Use of modern tomato breeding germplasm for deciphering the genetic control of agronomical traits by Genome Wide Association study.

    Science.gov (United States)

    Bauchet, Guillaume; Grenier, Stéphane; Samson, Nicolas; Bonnet, Julien; Grivet, Laurent; Causse, Mathilde

    2017-05-01

    A panel of 300 tomato accessions including breeding materials was built and characterized with >11,000 SNP. A population structure in six subgroups was identified. Strong heterogeneity in linkage disequilibrium and recombination landscape among groups and chromosomes was shown. GWAS identified several associations for fruit weight, earliness and plant growth. Genome-wide association studies (GWAS) have become a method of choice in quantitative trait dissection. First limited to highly polymorphic and outcrossing species, it is now applied in horticultural crops, notably in tomato. Until now GWAS in tomato has been performed on panels of heirloom and wild accessions. Using modern breeding materials would be of direct interest for breeding purpose. To implement GWAS on a large panel of 300 tomato accessions including 168 breeding lines, this study assessed the genetic diversity and linkage disequilibrium decay and revealed the population structure and performed GWA experiment. Genetic diversity and population structure analyses were based on molecular markers (>11,000 SNP) covering the whole genome. Six genetic subgroups were revealed and associated to traits of agronomical interest, such as fruit weight and disease resistance. Estimates of linkage disequilibrium highlighted the heterogeneity of its decay among genetic subgroups. Haplotype definition allowed a fine characterization of the groups and their recombination landscape revealing the patterns of admixture along the genome. Selection footprints showed results in congruence with introgressions. Taken together, all these elements refined our knowledge of the genetic material included in this panel and allowed the identification of several associations for fruit weight, plant growth and earliness, deciphering the genetic architecture of these complex traits and identifying several new loci useful for tomato breeding.

  15. Decreasing perinatal mortality in The Netherlands, 2000-2006: a record linkage study

    NARCIS (Netherlands)

    Ravelli, A.C.J.; Tromp, M.; van Huis, M.; Steegers, E.A.P.; Tamminga, P.; Eskes, M.; Bonsel, G.J.

    2009-01-01

    Background: The European PERISTAT-1 study showed that, in 1999, perinatal mortality, especially fetal mortality, was substantially higher in The Netherlands than in other European countries. The aim of this study was to analyse the recent trend in Dutch perinatal mortality and the influence of risk

  16. Knowledge linkage structures in communication studies using citation analysis among communication journals

    CERN Document Server

    Park, Han

    2009-01-01

    This research analyzes a "who cites whom" matrix in terms of aggregated, journal-journal citations to determine the location of communication studies on the academic spectrum. Using the Journal of Communication as the seed journal, the 2006 data in the Journal Citation Reports are used to map communication studies. The results show that social and experimental psychology journals are the most frequently used sources of information in this field. In addition, several journals devoted to the use and effects of media and advertising are weakly integrated into the larger communication research community, whereas communication studies are dominated by American journals.

  17. The genetic study of three population microisolates in South Tyrol (MICROS: study design and epidemiological perspectives

    Directory of Open Access Journals (Sweden)

    Pinggera Gerd K

    2007-06-01

    Full Text Available Abstract Background There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries. Methods The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03 genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL were undertaken. Results Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each. A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%. Conclusion The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a

  18. Estimating the risk of crime and victimisation in people with intellectual disability: a data-linkage study.

    Science.gov (United States)

    Nixon, Margaret; Thomas, Stuart D M; Daffern, Michael; Ogloff, James R P

    2017-05-01

    People with intellectual disability (PWID) appear more likely to be victims and perpetrators of crime. However, extant evidence pertaining to these risks is limited by methodological weaknesses and the absence of consistent operational definitions. This research aimed to estimate the prevalence of criminal histories and victimisation using a large, well-defined sample of PWID. A case-linkage study was conducted comprising 2220 PWID registered with disability services in Victoria, Australia, whose personal details were linked with a state-wide police database. Criminal charges and reports of victimisation were compared to a non-disabled community comparison sample (n = 2085). PWID were at increased risk of having a history of criminal charges, particularly for violent and sexual offences. Although the non-disabled comparison group had a greater risk of criminal victimisation overall, PWID had a greatly increased risk of sexual and violent crime victimisation. PWID are at increased risk of victimisation and perpetration of violent and sexual crimes. Risk of sex offending and victimisation is particularly elevated, and signalling the need for specialised interventions to prevent offending and to ensure victims is assisted with access to justice, support, and treatment.

  19. Observations From The Field: Further Developing Linkages Between Soil C models with Long-Term Bioenergy Studies

    Science.gov (United States)

    Schmer, M.; Jin, V.; Wienhold, B.

    2015-12-01

    Biofuel feedstocks are being developed and evaluated in the United States and Europe to partially offset petroleum transport fuels. Accurate accounting of upstream and downstream greenhouse gas (GHG) emissions is necessary to measure the overall carbon intensity of new biofuel feedstocks. Changes in direct soil organic carbon (SOC) can have a major impact on estimating overall greenhouse gas (GHG) emissions from biofuels when using life-cycle assessment (LCA). Estimating changes in SOC, when accounted for in a LCA, is largely derived from near-surface soil depths , typically to a depth of 30 cm or less. The majority of soil models do not model SOC changes below near-surface soil depths. Perennial herbaceous roots often extend much deeper than 30 cm and changes in cumulative SOC stocks may not be fully accounted for. Further, there is limited empirical data to validate SOC changes at soil depth from bioenergy crops with soil C models. Further calibration, validation, and intercomparisons of soil C models with long-term, field-based bioenergy studies are needed to accurately predict SOC stock changes at depth under variable soil types, climates, and cropping systems. From a LCA perspective, determining SOC stock changes at sub-surface depths would be a logical step to accurately quantify biofuel GHG emissions especially in bioenergy cropping systems with high potential for soil C storage. Presentation objectives will look at developing linkages and determining research needs from field-based SOC changes to modeling and looking at future landscapes with increased bioenergy feedstocks.

  20. A first insight into population structure and linkage disequilibrium in the US peanut minicore collection

    Science.gov (United States)

    Knowledge of genetic diversity, population structure, and degree of linkage disequilibrium (LD) in target association mapping populations is of great importance and is a prerequisite for LD-based mapping. In the present study, 96 genotypes comprising 92 accessions of the US peanut minicore collectio...

  1. Knowledge linkage structures in communication studies using citation analysis among communication journals

    NARCIS (Netherlands)

    Park, H.W.; Leydesdorff, L.

    2009-01-01

    This research analyzes a "who cites whom" matrix in terms of aggregated journal-journal citations to determine the location of communication studies on the academic spectrum. Using the Journal of Communication as the seed journal, the 2006 data in the Journal Citation Reports are used to map communi

  2. A linkage study of schizophrenia candidate regions in a Chinese multiplex pedigree

    Institute of Scientific and Technical Information of China (English)

    唐劲松

    2006-01-01

    Objective This study is to explore the molecular ge- netic relationship between chromosome regions and susceptibility genes for familial schizophrenia in Chinese Hah population. Methods A multiplex schizophrenia family including 5 schizophrenia patients and their 21 relatives was included. The patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders 4th Edi-

  3. Genome-wide linkage scan for loci associated with epilepsy in Belgian shepherd dogs

    Directory of Open Access Journals (Sweden)

    Regan Kelly R

    2010-05-01

    Full Text Available Abstract Background Idiopathic epilepsy in the Belgian shepherd dog is known to have a substantial genetic component. The objective of this study was to identify genomic regions associated with the expression of generalized seizures in the Belgian Tervuren and Sheepdog. Results DNA from 366 dogs, of which 74 were classified as epileptic, representing two extended families were subjected to a genome-wide linkage scan using 410 microsatellite markers yielding informative coverage averaging 5.95 ± 0.21 Mb. Though previous studies based on pedigree analyses proposed a major gene of influence, the present study demonstrated the trait to be highly polygenic. Studies of complex disorders in humans indicate that a liberal composite evaluation of genetic linkage is needed to identify underlying quantitative trait loci (QTLs. Four chromosomes yielded tentative linkage based upon LOD scores in excess of 1.0. Possible QTLs within these regions were supported also by analyses of multipoint linkage, allele frequency, TDT, and transmission of haplotype blocks. Conclusions Taken together the data tentatively indicate six QTLs, three on CFA 2, and one on each of CFA 6, 12, and 37, that support fine mapping for mutations associated with epilepsy in the Belgian shepherd. The study also underscores the complexity of genomic linkage studies for polygenic disorders.

  4. 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.

  5. Increasing incidence and mortality of infective endocarditis: a population-based study through a record-linkage system

    Directory of Open Access Journals (Sweden)

    Buonfrate Dora

    2011-02-01

    Full Text Available Abstract Background Few population-based studies provide epidemiological data on infective endocarditis (IE. Aim of the study is to analyze incidence and outcomes of IE in the Veneto Region (North-Eastern Italy. Methods Residents with a first hospitalization for IE in 2000-2008 were extracted from discharge data and linked to mortality records to estimate 365-days survival. Etiology was retrieved in subsets of this cohort by discharge codes and by linkage to a microbiological database. Risk factors for mortality were assessed through logistic regression. Results 1,863 subjects were hospitalized for IE, with a corresponding crude rate of 4.4 per 100,000 person-years, increasing from 4.1 in 2000-2002 to 4.9 in 2006-2008 (p = 0.003. Median age was 68 years; 39% of subjects were hospitalized in the three preceding months. 23% of patients underwent a cardiac valve procedure in the index admission or in the following year. Inhospital mortality was 14% (19% including hospital transfers; 90-days and 365-days mortality rose through the study years. Mortality increased with age and the Charlson comorbidity index, in subjects with previous hospitalizations for heart failure, and (in the subcohort with microbiological data in IE due to Staphylococci (40% of IE. Conclusions The study demonstrates an increasing incidence and mortality for IE over the last decade. Analyses of electronic archives provide a region-wide picture of IE, overcoming referral biases affecting single clinic or multicentric studies, and therefore represent a first fundamental step to detect critical issues related to IE.

  6. Suicide risk in relation to level of urbanicity - a population-based linkage study

    DEFF Research Database (Denmark)

    Qin, Ping

    2005-01-01

    from various Danish longitudinal registers. Data were analysed with conditional logistic regression. RESULTS: This study confirms that people living in more urbanized areas are at a higher risk of suicide than their counterparts in less urbanized areas. However, this excess risk is largely eliminated...... when adjusted for personal marital, income, and ethnic differences; it is even reversed when further adjusted for psychiatric status. Moreover, the impact of urbanicity on suicide risk differs significantly by sex and across age. Urban living reduces suicide risk significantly among men, especially...

  7. A satellite based study of tropospheric bromine explosion events and their linkages to polar cyclone development

    Science.gov (United States)

    Blechschmidt, Anne-Marlene; Richter, Andreas; Burrows, John P.; Kaleschke, Lars; Strong, Kimberly; Theys, Nicolas; Weber, Mark; Zhao, Xiaoyi; Zien, Achim; Hodges, Kevin I.

    2016-04-01

    Intense, cyclone-like shaped plumes of tropospheric bromine monoxide (BrO) are regularly observed by the UV-vis satellite instruments GOME-2/MetOp-A and SCIAMACHY/Envisat over Arctic and Antarctic sea ice in polar spring. The plumes are associated with an autocatalytic chemical chain reaction involving tropospheric ozone depletion and initiated by the release of bromine from cold brine-covered ice or snow to the atmosphere. This influences atmospheric chemistry as it affects the oxidising capacity of the troposphere through OH production and may also influence the local weather/temperature of the polar atmosphere, as ozone is a major greenhouse gas. Here, we make combined use of satellite retrievals and numerical model simulations to study individual BrO plume cases in the polar atmosphere. In agreement with previous studies, our analysis shows that the plumes are often transported by high latitude cyclones, sometimes over several days despite the short atmospheric lifetime of BrO. Moreover, general characteristics of bromine explosion events linked to transport by polar weather systems, such as frequency, spatial distribution and favourable weather conditions are derived based on a new detection method. Our results show that BrO cyclone transport events are by far more common in the Antarctic than in the Arctic.

  8. ABO Blood Group and Dementia Risk--A Scandinavian Record-Linkage Study

    DEFF Research Database (Denmark)

    Vasan, Senthil K; Rostgaard, Klaus; Ullum, Henrik;

    2015-01-01

    BACKGROUND: Dementia includes a group of neuro-degenerative disorders characterized by varying degrees of cognitive impairment. Recent data indicates that blood group AB is associated with impaired cognition in elderly patients. To date there are no large-scale studies that have examined the rela......BACKGROUND: Dementia includes a group of neuro-degenerative disorders characterized by varying degrees of cognitive impairment. Recent data indicates that blood group AB is associated with impaired cognition in elderly patients. To date there are no large-scale studies that have examined...... the relationship between ABO blood group and dementia-related disorders in detail. METHODS: We used data from the SCANDAT2 database that contains information on over 1.6 million blood donors from 1968 in Sweden and 1981 from Denmark. The database was linked with health outcomes data from nationwide patient...... and cause of death registers to investigate the relationship between blood groups and risk of different types of dementia. The incident rate ratios were estimated using log-linear Poisson regression models. RESULTS: Among 1,598,294 donors followed over 24 million person-years of observation we ascertained 3...

  9. Increasing prevalence of coeliac disease in Denmark: a linkage study combining national registries

    DEFF Research Database (Denmark)

    Dydensborg, Stine; Toftedal, Peter; Biaggi, Matteo

    2011-01-01

    Aim:  To determine the prevalence and incidence of diagnosed coeliac disease (CD) in Danish children and adolescents and to describe trends over time. Methods:  All children with a CD diagnosis registered in the Danish National Patient Registry (DNPR) were included in the study. Data were validated....... The mean age at diagnosis increased from 5.1 [95% CI 3.5-6.6] to 8.1 [95% CI 7.2-9.0] years of age. The proportion of children with associated diseases did not change over time. Conclusion:  The prevalence of diagnosed CD in Danish children and adolescents has increased over the last 15 years....

  10. ABO Blood Group and Dementia Risk--A Scandinavian Record-Linkage Study.

    Directory of Open Access Journals (Sweden)

    Senthil K Vasan

    Full Text Available Dementia includes a group of neuro-degenerative disorders characterized by varying degrees of cognitive impairment. Recent data indicates that blood group AB is associated with impaired cognition in elderly patients. To date there are no large-scale studies that have examined the relationship between ABO blood group and dementia-related disorders in detail.We used data from the SCANDAT2 database that contains information on over 1.6 million blood donors from 1968 in Sweden and 1981 from Denmark. The database was linked with health outcomes data from nationwide patient and cause of death registers to investigate the relationship between blood groups and risk of different types of dementia. The incident rate ratios were estimated using log-linear Poisson regression models.Among 1,598,294 donors followed over 24 million person-years of observation we ascertained 3,615 cases of Alzheimer's disease, 1,842 cases of vascular dementia, and 9,091 cases of unspecified dementia. Overall, our study showed no association between ABO blood group and risk of Alzheimer's disease, vascular dementia or unspecified dementia. This was also true when analyses were restricted to donors aged 70 years or older except for a slight, but significantly decreased risk of all dementia combined in subjects with blood group A (IRR, 0.93; 95% confidence interval [CI], 0.88-0.98, compared to those with blood group O.Our results provide no evidence that ABO blood group influences the risk of dementia.

  11. Cigarette smoking and tooth loss experience among young adults: a national record linkage study

    Directory of Open Access Journals (Sweden)

    Tanaka Keiko

    2007-11-01

    Full Text Available Abstract Background Various factors affect tooth loss in older age including cigarette smoking; however, evidence regarding the association between smoking and tooth loss during young adulthood is limited. The present study examined the association between cigarette smoking and tooth loss experience among adults aged 20–39 years using linked data from two national databases in Japan. Methods Two databases of the National Nutrition Survey (NNS and the Survey of Dental Diseases (SDD, which were conducted in 1999, were obtained from the Ministry of Health, Labor and Welfare with permission for analytical use. In the NNS, participants received physical examinations and were interviewed regarding dietary intake and health practices including cigarette smoking, whereas in the SDD, participants were asked about their frequency of daily brushing, and received oral examinations by certified dentists. Among 6,805 records electronically linked via household identification code, 1314 records of individuals aged 20 to 39 years were analyzed. The prevalence of 1+ tooth loss was compared among non-, former, and current smokers. Multiple logistic regression models were constructed including confounders: frequency of tooth brushing, body mass index, alcohol consumption, and intake of vitamins C and E. Results Smoking rates differed greatly in men (53.3% and women (15.5%. The overall prevalence of tooth loss was 31.4% (31.8% men and 31.1% women. Tooth loss occurred more frequently among current smokers (40.6% than former (23.1% and non-smokers (27.9%. Current smoking showed a significant association with 1+ tooth loss in men (adjusted OR = 2.21 [1.40–3.50], P = 0.0007 and women (1.70 [1.13–2.55], P = 0.0111. A significant positive exposure-related relationship between cigarette smoking status and tooth loss was observed (P for trend Conclusion An association between cigarette smoking and tooth loss was evident among young adults throughout Japan. Due to

  12. Adaptive Linkage Disequilibrium Between Two Esterase Loci of a Salamander

    Science.gov (United States)

    Webster, T. Preston

    1973-01-01

    In some populations of the salamander Plethodon cinereus, two polymorphic esterase loci are in linkage disequilibrium. Short-term stability of the linkage disequilibrium is demonstrated by an age class analysis. Long, perhaps very long, term stability is suggested by its distribution. This stability and concordant geographic variation in allelic frequencies imply selective origin and maintenance. Data on the frequencies of two color morphs suggest that formation of the linkage disequilibrium is dependent on the genetic background. Images PMID:4515614

  13. A photoactive isoprenoid diphosphate analogue containing a stable phosphonate linkage: synthesis and biochemical studies with prenyltransferases

    Science.gov (United States)

    DeGraw, Amanda J.; Zhao, Zongbao; Strickland, Corey L.; Taban, A. Huma; Hsieh, John; Michael, Jefferies; Xie, Wenshuang; Shintani, David; McMahan, Colleen; Cornish, Katrina; Distefano, Mark D.

    2008-01-01

    A number of biochemical processes rely on isoprenoids, including the post-translational modification of signaling proteins and the biosynthesis of a wide array of compounds. Photoactivatable analogues have been developed to study isoprenoid utilizing enzymes such as the isoprenoid synthases and prenyltransferases. While these initial analogues proved to be excellent structural analogues with good cross linking capability, they lack the stability needed when the goals include isolation of cross-linked species, tryptic digestion, and subsequent peptide sequencing. Here, the synthesis of a benzophenone-based farnesyl diphosphate analogue containing a stable phosphonophosphate group is described. Inhibition kinetics, photolabeling experiments, as well as x-ray crystallographic analysis with a protein prenyltransferase are described, verifying this compound as a good isoprenoid mimetic. In addition, the utility of this new analogue was explored by using it to photoaffinity label crude protein extracts obtained from Hevea brasiliensis latex. Those experiments suggest that a small protein, Rubber Elongation Factor, interacts directly with farnesyl diphosphate during rubber biosynthesis. These results indicate that this benzophenone-based isoprenoid analogue will be useful for identifying enzymes that utilize farnesyl diphosphate as a substrate. PMID:17477573

  14. Clostridium difficile Infections amongst Patients with Haematological Malignancies: A Data Linkage Study.

    Directory of Open Access Journals (Sweden)

    Linda A Selvey

    Full Text Available Identify risk factors for Clostridium difficile infection (CDI and assess CDI outcomes among Australian patients with a haematological malignancy.A retrospective cohort study involving all patients admitted to hospitals in Western Australia with a haematological malignancy from July 2011 to June 2012. Hospital admission data were linked with all hospital investigated CDI case data. Potential risk factors were assessed by logistic regression. The risk of death within 60 and 90 days of CDI was assessed by Cox Proportional Hazards regression.There were 2085 patients of whom 65 had at least one CDI. Twenty percent of CDI cases were either community-acquired, indeterminate source or had only single-day admissions in the 28 days prior to CDI. Using logistic regression, having acute lymphocytic leukaemia, neutropenia and having had bacterial pneumonia or another bacterial infection were associated with CDI. CDI was associated with an increased risk of death within 60 and 90 days post CDI, but only two deaths had CDI recorded as an antecedent factor. Ribotyping information was available for 33 of the 65 CDIs. There were 19 different ribotypes identified.Neutropenia was strongly associated with CDI. While having CDI is a risk factor for death, in many cases it may not be a direct contributor to death but may reflect patients having higher morbidity. A wide variety of C. difficile ribotypes were found and community-acquired infection may be under-estimated in these patients.

  15. Bayesian linkage analysis of categorical traits for arbitrary pedigree designs.

    Directory of Open Access Journals (Sweden)

    Abra Brisbin

    Full Text Available BACKGROUND: Pedigree studies of complex heritable diseases often feature nominal or ordinal phenotypic measurements and missing genetic marker or phenotype data. METHODOLOGY: We have developed a Bayesian method for Linkage analysis of Ordinal and Categorical traits (LOCate that can analyze complex genealogical structure for family groups and incorporate missing data. LOCate uses a Gibbs sampling approach to assess linkage, incorporating a simulated tempering algorithm for fast mixing. While our treatment is Bayesian, we develop a LOD (log of odds score estimator for assessing linkage from Gibbs sampling that is highly accurate for simulated data. LOCate is applicable to linkage analysis for ordinal or nominal traits, a versatility which we demonstrate by analyzing simulated data with a nominal trait, on which LOCate outperforms LOT, an existing method which is designed for ordinal traits. We additionally demonstrate our method's versatility by analyzing a candidate locus (D2S1788 for panic disorder in humans, in a dataset with a large amount of missing data, which LOT was unable to handle. CONCLUSION: LOCate's accuracy and applicability to both ordinal and nominal traits will prove useful to researchers interested in mapping loci for categorical traits.

  16. Antecedents of teenage pregnancy from a 14-year follow-up study using data linkage

    Directory of Open Access Journals (Sweden)

    Stanley Fiona J

    2010-02-01

    Full Text Available Abstract Background Many western nations continue to have high rates of teenage pregnancies and births, which can result in adverse outcomes for both mother and child. This study identified possible antecedents of teenage pregnancy using linked data from administrative sources to create a 14-year follow-up from a cross-sectional survey. Methods Data were drawn from two sources - the 1993 Western Australian Child Health Survey (WACHS, a population-based representative sample of 2,736 children aged 4 to 16 years (1,374 girls; and administrative data relating to all their subsequent births and hospital admissions. We used weighted population estimates to examine differences between rates for teenage pregnancy, motherhood and abortion. We used Cox proportional hazards regression to model risk for teenage pregnancy. Results There were 155 girls aged less than 20 years at the time of their first recorded pregnancy. Teenage pregnancy was significantly associated with: family type; highest school year completed by primary carer; combined carer income; whether the primary carer was a smoker; and whether the girl herself displayed aggressive and delinquent behaviours. An age-interaction analysis on the association with aggressive and delinquent behaviours found that while girls with aggressive and delinquent behaviours who were older at the time of the survey were at highest risk of teenage pregnancy, there was elevated risk for future teenage pregnancy across all ages. Conclusions Our findings suggest that interventions to reduce teenage pregnancy rates could be introduced during primary school years, including those that are focused on the prevention and management of aggressive and delinquent behaviour.

  17. Antecedents of teenage pregnancy from a 14-year follow-up study using data linkage.

    Science.gov (United States)

    Gaudie, Jennifer; Mitrou, Francis; Lawrence, David; Stanley, Fiona J; Silburn, Sven R; Zubrick, Stephen R

    2010-02-11

    Many western nations continue to have high rates of teenage pregnancies and births, which can result in adverse outcomes for both mother and child. This study identified possible antecedents of teenage pregnancy using linked data from administrative sources to create a 14-year follow-up from a cross-sectional survey. Data were drawn from two sources - the 1993 Western Australian Child Health Survey (WACHS), a population-based representative sample of 2,736 children aged 4 to 16 years (1,374 girls); and administrative data relating to all their subsequent births and hospital admissions. We used weighted population estimates to examine differences between rates for teenage pregnancy, motherhood and abortion. We used Cox proportional hazards regression to model risk for teenage pregnancy. There were 155 girls aged less than 20 years at the time of their first recorded pregnancy. Teenage pregnancy was significantly associated with: family type; highest school year completed by primary carer; combined carer income; whether the primary carer was a smoker; and whether the girl herself displayed aggressive and delinquent behaviours. An age-interaction analysis on the association with aggressive and delinquent behaviours found that while girls with aggressive and delinquent behaviours who were older at the time of the survey were at highest risk of teenage pregnancy, there was elevated risk for future teenage pregnancy across all ages. Our findings suggest that interventions to reduce teenage pregnancy rates could be introduced during primary school years, including those that are focused on the prevention and management of aggressive and delinquent behaviour.

  18. Workplace bullying and subsequent psychotropic medication: a cohort study with register linkages

    Science.gov (United States)

    Lallukka, Tea; Haukka, Jari; Partonen, Timo; Rahkonen, Ossi; Lahelma, Eero

    2012-01-01

    Objectives We aimed to examine longitudinally whether workplace bullying was associated with subsequent psychotropic medication among women and men. Design A cohort study. Setting Helsinki, Finland. Participants Employees of the City of Helsinki, Finland (n=6606, 80% women), 40–60 years at baseline in 2000–2002, and a register-based follow-up on medication. Primary and secondary outcome measures Workplace bullying comprised questions about current and earlier bullying as well as observing bullying. The Finnish Social Insurance Institution's register data on purchases of prescribed reimbursed psychotropic medication were linked with the survey data. All psychotropic medication 3 years prior to and 5 years after the baseline survey was included. Covariates included age, prior psychotropic medication, childhood bullying, occupational class, and body mass index. Cox proportional hazard models (HR, 95% CI) were fitted and days until the first purchase of prescribed psychotropic medication after baseline were used as the time axis. Results Workplace bullying was associated with subsequent psychotropic medication after adjusting for age and prior medication among both women (HR 1.51, 95% CI 1.18 to 1.93) and men (HR 2.15, 95% CI 1.36 to 3.41). Also observing bullying was associated with subsequent psychotropic medication among women (HR 1.53, 95% CI 1.25 to 1.88) and men (HR 1.92, 95% CI 1.23 to 2.99). The associations only modestly attenuated after full adjustment. Conclusions Our findings highlight the significance of workplace bullying to subsequent psychotropic medication reflecting medically confirmed mental problems. Tackling workplace bullying likely helps prevent mental problems among employees. PMID:23242240

  19. Working conditions as risk factors for disability retirement: a longitudinal register linkage study

    Directory of Open Access Journals (Sweden)

    Lahelma Eero

    2012-04-01

    Full Text Available Abstract Background Early retirement due to disability is a public health and work environment problem that shortens working careers. Transition to disability retirement is based on ill-health, but working conditions are also of relevance. We examined the contributions of work arrangements, physical working conditions and psychosocial working conditions to subsequent disability retirement. Methods The data were derived from the Helsinki Health Study cohort on employees of the City of Helsinki, Finland. Information on working conditions was obtained from the baseline surveys conducted in 2000, 2001 and 2002. These data were linked with register data on disability retirement and their main diagnoses obtained from the Finnish Centre for Pensions. Follow up by the end of 2008 yielded 525 disability retirement events. The analysed data included 6525 participants and 525 disability retirement events. Hazard ratios (HR and 95% confidence intervals (95% CI were calculated from Cox regression analysis. Results Several working conditions showed own associations with disability retirement before adjustment. After adjustment for all working conditions, the primary risk factors for all-cause disability retirement were physical workload among women (HR 2.02, 95% CI 1.57-2.59 and men (HR 2.00, 95% CI 1.18-3.38, and low job control among women (HR 1.60, 95% CI 1.29-1.99. In addition, for disability retirement due to musculoskeletal causes, the risk factors were physical workload and low job control. For disability retirement due to mental causes the risk factors were computer work and low job control. Furthermore, occupational class was a risk factor for disability retirement due to all causes and musculoskeletal diseases. Conclusions Among various working conditions, those that are physically demanding and those that imply low job control are potential risk factors for disability retirement. Improving the physical working environment and enhancing control over

  20. Aspects of record linkage

    NARCIS (Netherlands)

    Schraagen, Marijn Paul

    2014-01-01

    This thesis is an exploration of the subject of historical record linkage. The general goal of historical record linkage is to discover relations between historical entities in a database, for any specific definition of relation, entity and database. Although this task originates from historical

  1. Subsidiary Linkage Patterns

    DEFF Research Database (Denmark)

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

    2012-01-01

    This paper investigates the pattern of subsidiaries' local vertical linkages under varying levels of competition and subsidiary capabilities. Contrary to most previous literature, we explicitly account for the double role of such linkages as conduits of learning prospects as well as potential...

  2. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study

    Directory of Open Access Journals (Sweden)

    Handel Adam E

    2011-01-01

    Full Text Available Abstract Background Venous thromboembolism (VTE is a common complication during and after a hospital admission. Although it is mainly considered a complication of surgery, it often occurs in people who have not undergone surgery, with recent evidence suggesting that immune-mediated diseases may play a role in VTE risk. We, therefore, decided to study the risk of deep vein thrombosis (DVT and pulmonary embolism (PE in people admitted to hospital with a range of immune-mediated diseases. Methods We analysed databases of linked statistical records of hospital admissions and death certificates for the Oxford Record Linkage Study area (ORLS1:1968 to 1998 and ORLS2:1999 to 2008 and the whole of England (1999 to 2008. Rate ratios for VTE were determined, comparing immune-mediated disease cohorts with comparison cohorts. Results Significantly elevated risks of VTE were found, in all three populations studied, in people with a hospital record of admission for autoimmune haemolytic anaemia, chronic active hepatitis, dermatomyositis/polymyositis, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis, myxoedema, pemphigus/pemphigoid, polyarteritis nodosa, psoriasis, rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus. Rate ratios were considerably higher for some of these diseases than others: for example, for systemic lupus erythematosus the rate ratios were 3.61 (2.36 to 5.31 in the ORLS1 population, 4.60 (3.19 to 6.43 in ORLS2 and 3.71 (3.43 to 4.02 in the England dataset. Conclusions People admitted to hospital with immune-mediated diseases may be at an increased risk of subsequent VTE. Our findings need independent confirmation or refutation; but, if confirmed, there may be a role for thromboprophylaxis in some patients with these diseases.

  3. Cesarean Section and Risk of Childhood Acute Lymphoblastic Leukemia in a Population-Based, Record-Linkage Study in California.

    Science.gov (United States)

    Wang, Rong; Wiemels, Joseph L; Metayer, Catherine; Morimoto, Libby; Francis, Stephen S; Kadan-Lottick, Nina; DeWan, Andrew T; Zhang, Yawei; Ma, Xiaomei

    2017-01-15

    The relationship of mode of delivery to risk of childhood acute lymphoblastic leukemia (ALL) is uncertain. After linking birth records and cancer registry data from California, we conducted a population-based case-control study to investigate the role of delivery by cesarean section (C-section) in the etiology of childhood ALL. This study included 5,081 cases and 18,927 matched controls born in 1978-2009; more detailed data were available on type of C-section (i.e., elective vs. emergency) for a subset of 1,552 cases and 5,688 controls. No association was observed between C-section overall and childhood ALL risk (section was associated with a significantly elevated risk of ALL (odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.01, 1.36). At the peak ages of ALL incidence (2-4 years), C-section was associated with an 11% higher risk of ALL (OR = 1.11, 95% CI: 1.01, 1.22) compared with vaginal delivery, and the magnitude of the association was larger for elective C-section (OR = 1.38, 95% CI: 1.11, 1.70). Emergency C-section was not associated with childhood ALL. Because of design features minimizing nonparticipation and inaccurate recall, this record linkage-based study is less prone to bias. Our results suggest that delivery by elective C-section was associated with a higher risk of childhood ALL, especially at the peak ages of incidence. It is important to evaluate possible mechanisms, because this potential risk factor is modifiable. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Genetic studies of two inherited human phenotypes : Hearing loss and monoamine oxidase activity

    OpenAIRE

    Balciuniene, Jorune

    2001-01-01

    This thesis focuses on the identification of genetic factors underlying two inherited human phenotypes: hearing loss and monoamine oxidase activity. Non-syndromic hearing loss segregating in a Swedish family was tested for linkage to 13 previously reported candidate loci for hearing disabilities. Linkage was found to two loci: DFNA12 (llq22-q24) and DFNA2 (lp32). A detailed analysis of the phenotypes and haplotypes shared by the affected individuals supported the hypothesis of digenic inheri...

  5. Of River Linkage and Issue Linkage

    NARCIS (Netherlands)

    Warner, Jeroen Frank

    2016-01-01

    It is a truism in mainstream International Relations that issue linkage promotes regime formation and integration. The present article applies this idea to the transboundary lower river Meuse and finds its history of integration to be a tortuous one. Contextual political factors have at times

  6. Extent of linkage disequilibrium in chicken

    NARCIS (Netherlands)

    Aerts, J.; Megens, H.J.W.C.; Veenendaal, T.; Ovcharenko, I.; Crooijmans, R.P.M.A.; Gordon, L.; Stubbs, L.; Groenen, M.A.M.; Rodoinov, A.; Gaginskaya, E.

    2007-01-01

    Many of the economically important traits in chicken are multifactorial and governed by multiple genes located at different quantitative trait loci (QTLs). The optimal marker density to identify these QTLs in linkage and association studies is largely determined by the extent of linkage

  7. A Genetic Linkage Map for Naked Oat (Avena nuda L.)%大粒裸燕麦(Avena nuda L.)遗传连锁图谱的构建

    Institute of Scientific and Technical Information of China (English)

    徐微; 张宗文; 张恩来; 吴斌

    2013-01-01

    Based on 281 individual plants of F2 population derived from a cross "Yuan Naked Oat"x"555",a genetic linkage map for naked oat (Avena nuda L.) was constructed by 20 AFLP primer pairs,3 SSR primer pairs,and 1 panicle type character.The map was 1544.8 cM in total length with 20.1 cM for the average distance between neighboring markers.92 AFLP markers,3 SSR markers,and 1 morphological trait were mapped on 19 linkage groups,which contained 2-14 markers and varied in size from 23.7 cM to 276.3 cM with an average of 81.3 cM.The segregation ratio of panicle type fitted to 3:1,and 11 AFLP markers demonstrated distorted segregation with the percentage of 11.5%.The results provided a framework of genetic linkage map for naked oat (Avena nuda L.),which was the theoretical basis for QTL mapping,molecular breeding,and comparative genomics in naked oat research.%以元莜麦和555杂交得到的281个F2单株为作图群体,利用20对AFLP引物、3对SSR引物和1个穗型性状构建了一张大粒裸燕麦遗传连锁图.该图谱全长1544.8 cM,包含19个连锁群,其上分布有92个AFLP标记、3个SSR标记和1个穗型形态标记,不同连锁群标记数为2 ~14个,长度在23.7 ~276.3 cM之间,平均长度为81.3 cM,标记间平均距离为20.1 cM.穗型标记分离比符合3:1,11个AFLP标记表现为偏分离,偏分离比为11.5%.该图谱符合遗传连锁框架图的要求,为今后大粒裸燕麦的QTL定位、分子标记辅助育种和比较基因组学等研究奠定基础.

  8. High Hospitalization Rates in Survivors of Childhood Cancer: A Longitudinal Follow-Up Study Using Medical Record Linkage.

    Science.gov (United States)

    Sieswerda, Elske; Font-Gonzalez, Anna; Reitsma, Johannes B; Dijkgraaf, Marcel G W; Heinen, Richard C; Jaspers, Monique W; van der Pal, Helena J; van Leeuwen, Flora E; Caron, Huib N; Geskus, Ronald B; Kremer, Leontien C

    2016-01-01

    Hospitalization rates over time of childhood cancer survivors (CCS) provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR) was 2.2 (95%CI:1.9-2.5) for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5-10 and 20-30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1-16.3) and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6-11.7). Female gender (P<0.001), radiotherapy to head and/or neck (P<0.001) or thorax and/or abdomen (P = 0.03) and surgery (P = 0.01) were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources.

  9. High Hospitalization Rates in Survivors of Childhood Cancer: A Longitudinal Follow-Up Study Using Medical Record Linkage.

    Directory of Open Access Journals (Sweden)

    Elske Sieswerda

    Full Text Available Hospitalization rates over time of childhood cancer survivors (CCS provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR was 2.2 (95%CI:1.9-2.5 for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5-10 and 20-30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1-16.3 and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6-11.7. Female gender (P<0.001, radiotherapy to head and/or neck (P<0.001 or thorax and/or abdomen (P = 0.03 and surgery (P = 0.01 were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources.

  10. Population structure and linkage disequilibrium in oat (Avena sativa L.): implications for genome-wide association studies.

    Science.gov (United States)

    Newell, M A; Cook, D; Tinker, N A; Jannink, J-L

    2011-02-01

    The level of population structure and the extent of linkage disequilibrium (LD) can have large impacts on the power, resolution, and design of genome-wide association studies (GWAS) in plants. Until recently, the topics of LD and population structure have not been explored in oat due to the lack of a high-throughput, high-density marker system. The objectives of this research were to survey the level of population structure and the extent of LD in oat germplasm and determine their implications for GWAS. In total, 1,205 lines and 402 diversity array technology (DArT) markers were used to explore population structure. Principal component analysis and model-based cluster analysis of these data indicated that, for the lines used in this study, relatively weak population structure exists. To explore LD decay, map distances of 2,225 linked DArT marker pairs were compared with LD (estimated as r²). Results showed that LD between linked markers decayed rapidly to r² = 0.2 for marker pairs with a map distance of 1.0 centi-Morgan (cM). For GWAS, we suggest a minimum of one marker every cM, but higher densities of markers should increase marker-QTL association and therefore detection power. Additionally, it was found that LD was relatively consistent across the majority of germplasm clusters. These findings suggest that GWAS in oat can include germplasm with diverse origins and backgrounds. The results from this research demonstrate the feasibility of GWAS and related analyses in oat.

  11. High Hospitalization Rates in Survivors of Childhood Cancer: A Longitudinal Follow-Up Study Using Medical Record Linkage

    Science.gov (United States)

    Sieswerda, Elske; Font-Gonzalez, Anna; Reitsma, Johannes B.; Dijkgraaf, Marcel G. W.; Heinen, Richard C.; Jaspers, Monique W.; van der Pal, Helena J.; van Leeuwen, Flora E.; Caron, Huib N.

    2016-01-01

    Hospitalization rates over time of childhood cancer survivors (CCS) provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR) was 2.2 (95%CI:1.9–2.5) for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5–10 and 20–30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1–16.3) and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6–11.7). Female gender (P<0.001), radiotherapy to head and/or neck (P<0.001) or thorax and/or abdomen (P = 0.03) and surgery (P = 0.01) were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources. PMID:27433937

  12. Linkage to Primary Care and Survival After Hospital Discharge for HIV-Infected Adults in Tanzania: A Prospective Cohort Study.

    Science.gov (United States)

    Peck, Robert N; Wang, Richard J; Mtui, Graham; Smart, Luke; Yango, Missana; Elchaki, Rim; Wajanga, Bahati; Downs, Jennifer A; Mteta, Kien; Fitzgerald, Daniel W

    2016-12-15

    Little is known about outcomes after hospitalization for HIV-infected adults in sub-Saharan Africa. We determined 12-month, posthospital mortality rates in HIV-infected vs. uninfected adults and predictors of mortality. In this prospective cohort study, we enrolled adults admitted to the medical wards of a public hospital in northwestern Tanzania. We conducted standardized questionnaires, physical examinations, and basic laboratory analyses including HIV testing. Participants or proxies were called at 1, 3, 6, and 12 months to determine outcomes. Predictors of in-hospital and posthospital mortality were determined using logistic regression. Cox regression models were used to analyze mortality incidence and associated factors. To confirm our findings, we studied adults admitted to another government hospital. We enrolled 637 consecutive adult medical inpatients: 38/143 (26.6%) of the HIV-infected adults died in hospital vs. 104/494 (21.1%) of the HIV-uninfected adults. Twelve-month outcomes were determined for 98/105 (93.3%) vs. 352/390 (90.3%) discharged adults, respectively. Posthospital mortality was 53/105 (50.5%) for HIV-infected adults vs. 126/390 (32.3%) for HIV-uninfected adults (adjusted P = 0.006). The 66/105 (62.9%) HIV-infected adults who attended clinic within 1 month after discharge had significantly lower mortality than the other HIV-infected adults [adjusted hazards ratio = 0.17 (0.07-0.39), P Adults admitted to a nearby government hospital had similar high rates of posthospital mortality. Posthospital mortality is disturbingly high among HIV-infected adult inpatients in Tanzania. The posthospital period may offer a window of opportunity to improve survival in this population. Interventions are urgently needed and should focus on increasing posthospital linkage to primary HIV care.

  13. Globalization’s unexpected impact on soybean production in South America: linkages between preferences for non-genetically modified crops, eco-certifications, and land use

    Science.gov (United States)

    Garrett, Rachael D.; Rueda, Ximena; Lambin, Eric F.

    2013-12-01

    The land use impacts of globalization and of increasing global food and fuel demand depend on the trade relationships that emerge between consuming and producing countries. In the case of soybean production, increasing trade between South American farmers and consumers in Asia and Europe has facilitated soybean expansion in the Amazon, Chaco, and Cerrado biomes. While these telecouplings have been well documented, there is little understanding of how quality preferences influence trade patterns and supply chains, incentivizing or discouraging particular land use practices. In this study we provide empirical evidence that Brazil’s continued production of non-genetically modified (GM) soybeans has increased its competitive advantage in European countries with preferences against GM foods. Brazil’s strong trade relationship with European consumers has facilitated an upgrading of the soybean supply chain. Upgraded soybean supply chains create new conservation opportunities by allowing farmers to differentiate their products based on environmental quality in order to access premiums in niche markets in Europe. These interactions between GM preferences, trade flows, and supply chain structure help to explain why Brazilian soybean farmers have adopted environmental certification programs on a larger scale than Argentinian, Bolivian, Paraguayan, and Uruguayan soybean producers.

  14. Dubin's Minimal Linkage Construct Revisited.

    Science.gov (United States)

    Rogers, Donald P.

    This paper contains a theoretical analysis and empirical study that support the major premise of Robert Dubin's minimal-linkage construct-that restricting communication links increases organizational stability. The theoretical analysis shows that fewer communication links are associated with less uncertainty, more redundancy, and greater…

  15. 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...

  16. Study of Siberian forest genetic resources

    Directory of Open Access Journals (Sweden)

    L. I. Milyutin

    2016-06-01

    Full Text Available Forest genetic resources are the aggregate of genofonds of native and cultivar populations of forest woody plants, valuable really or potential for specific territory (A brief dictionary… 2014. Forest genetic resources are studied in practice in most cases on example of forest-forming woody plants. It is necessary to consider of study of these resources in two positions: taxonomic and geographic. Forest forming coniferous species are studied best of all from the taxonomic point of view taking into account biodiversity. Genetic polymorphism is studied most in detail with such species as Pinus sylvestris, Pinus sibirica, Larix sibirica, Larix sukaczevii, Picea obovata, Abies sibirica. Populations of Larix gmelinii, Larix cajanderi, Picea ajanensis are studied considerable worse. Materials about genetic polymorphism of forest forming foliage species – representative of genera Betula and Populus are absent. Caryological polymorphism is studied sufficiently well in all Siberian conifer species. It should be noted especially attached to examination of this problem, that individuals with B-chromosome were discovered first by gymnosperms as an example Picea obovata. Discovery in Siberia of triploid asp deserve special attention. Geographic variability is shown most broadly in the investigations of Pinus sylvestris, Pinus sibirica, Larix sibirica. These investigations were conducted both in natural populations and in provenance trials. Such investigations of another conifer and foliage species either are shown by separate fragments or are absent at all Geographic variability is shown in a large measure in the operative forest seed sources regionalization. Numerous investigations directed to the analysis of morphological variability are conducted by all forest forming species in the first place by conifers. Questions of hereditary determination of either signs remain in this problem. Similar questions concern the variability of other signs

  17. Indication of Genetic Linkage Map for Sunflower by SSR Markers%SSR分子标记丰富向日葵(Helianthus annuus L.)遗传图谱的研究

    Institute of Scientific and Technical Information of China (English)

    黄先群; Genzbitelle L.; Fabre F.; Saraffi A.

    2012-01-01

    为了提高向日葵遗传图谱的密度和实用性,以125个来源于PAC-2和RHA-266杂交的F(8)代重组自交系(RIIs)群体为材料,利用筒单序列重复(Simple sequence repeat,SSR)标记,采用MAPMARKER软件对向日英遗传图谱进行标注,并从300对SSR引物中筛选出51对多态性引物对群体进行标记.结果表明:①51对多态性引物中有19对引物无多态性或条带不清晰,32对引物表现多态性;②共检测到35个多态性位点,分布在图谱的15条连锁群上.③标记后的图谱总长度为2914.5 Cm,比原来的图谱增长7.5 Cm.④标记间平均距离由9.0 Cm缩短为8.1 Cm.%This study aimed to improve density and practicality of the genetic map of sunflower baaed on a 125 Fs RILa population derived from a cross between PAC-2 and RHA-266 by adding some SSR markers. A total of 300 pairs of SSR primers were used to screen polymorphic markers between the parents and some of their RILs, of which 51 pain of the primers showed polymorphism. The results of screening the RILs population revealed that 19 SSR primer without polymorphism or non-reading, 32 SSR pairs showed polymorphism with 35 alleles added into the map. They were distributed in the 15 linkage groups of the maps. The new map covered a total length of 2914.5 cM, 7.5 cM longer than the original map. The average distance between adjacent markers was 8.1 cM instead of original 9.0 cM.

  18. Risk of pneumonia and pneumococcal disease in people hospitalized with diabetes mellitus: English record-linkage studies.

    Science.gov (United States)

    Seminog, O O; Goldacre, M J

    2013-12-01

    The risk of invasive pneumococcal disease is higher in people with diabetes mellitus than those without. People with diabetes should be considered for routine pneumococcal immunization. This policy has been in place in England for more than a decade. We aimed to estimate, at the population level, the current scale of excess risk of pneumococcal disease in patients with diabetes, and whether the risks have decreased in recent years with the introduction of a pneumococcal vaccine. We used two data sets of linked hospital admission and death records-the Oxford Record Linkage Study (1963-1998) and all-England linked hospital episode statistics (1999-2011). As a measure of relative risk, we calculated the rate ratio of pneumococcal disease in cohorts of people hospitalized with diabetes compared with cohorts without a record of diabetes. The risk of pneumococcal disease in patients hospitalized with diabetes mellitus has declined a little, but it is still high. The all-ages rate ratio in England declined from 1.92 (95% CI 1.89-1.94) in 1999-2002 to 1.68 (95% CI 1.65-1.71) in 2007-2011. In people aged under 60 years, rate ratios were higher and their decline was more substantial: rate ratios declined from 3.37 (95% CI 3.28-3.46) in 1999-2002 to 2.33 (95% CI 2.21-2.45) in 2007-2011. Patients admitted to hospital with diabetes mellitus remain at increased risk of pneumococcal infection despite a national immunization policy. Possible explanations for the elevated risk include low vaccine uptake or low effectiveness of available vaccine. Clinicians should be aware of the risk of pneumococcal infection in people with diabetes. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  19. Association and linkage studies of the TAQI A1 allele at the dopamine D{sub 2} receptor gene in samples of female and male alcoholics

    Energy Technology Data Exchange (ETDEWEB)

    Neiswanger, K.; Hill, S.Y.; Kaplan, B.B. [Univ. of Pittsburgh, PA (United States)] [and others

    1995-08-14

    To address the controversy surrounding DRD2 and alcoholism, we performed linkage and association studies utilizing alcoholic men from high density families largely uncontaminated by other psychopathology and female alcoholics for whom secondary drug dependence (averaging 10 years later onset) was a prominent feature. The males and females were combined for a total of 52 alcoholics, and compared to 30 controls screened for the absence of alcoholism and other psychopathology, revealing a significant association between the frequency of the TaqI allele and alcoholism. However, linkage and family-based association study, placed in the context of the literature, suggest that minimizing psychopathology in control groups is probably a more important explanation for divergent results than either sampling error or population stratification. When combined with the complete lack of within-family evidence, we conclude that the association, while not specific to the alcoholism phenotype, per se. 37 refs., 2 tabs.

  20. A ddRAD Based Linkage Map of the Cultivated Strawberry, Fragaria xananassa.

    Directory of Open Access Journals (Sweden)

    Jahn Davik

    Full Text Available The cultivated strawberry (Fragaria ×ananassa Duch. is an allo-octoploid considered difficult to disentangle genetically due to its four relatively similar sub-genomic chromosome sets. This has been alleviated by the recent release of the strawberry IStraw90 whole genome genotyping array. However, array resolution relies on the genotypes used in the array construction and may be of limited general use. SNP detection based on reduced genomic sequencing approaches has the potential of providing better coverage in cases where the studied genotypes are only distantly related from the SNP array's construction foundation. Here we have used double digest restriction-associated DNA sequencing (ddRAD to identify SNPs in a 145 seedling F1 hybrid population raised from the cross between the cultivars Sonata (♀ and Babette (♂. A linkage map containing 907 markers which spanned 1,581.5 cM across 31 linkage groups representing the 28 chromosomes of the species. Comparing the physical span of the SNP markers with the F. vesca genome sequence, the linkage groups resolved covered 79% of the estimated 830 Mb of the F. × ananassa genome. Here, we have developed the first linkage map for F. × ananassa using ddRAD and show that this technique and other related techniques are useful tools for linkage map development and downstream genetic studies in the octoploid strawberry.

  1. A ddRAD Based Linkage Map of the Cultivated Strawberry, Fragaria xananassa.

    Science.gov (United States)

    Davik, Jahn; Sargent, Daniel James; Brurberg, May Bente; Lien, Sigbjørn; Kent, Matthew; Alsheikh, Muath

    2015-01-01

    The cultivated strawberry (Fragaria ×ananassa Duch.) is an allo-octoploid considered difficult to disentangle genetically due to its four relatively similar sub-genomic chromosome sets. This has been alleviated by the recent release of the strawberry IStraw90 whole genome genotyping array. However, array resolution relies on the genotypes used in the array construction and may be of limited general use. SNP detection based on reduced genomic sequencing approaches has the potential of providing better coverage in cases where the studied genotypes are only distantly related from the SNP array's construction foundation. Here we have used double digest restriction-associated DNA sequencing (ddRAD) to identify SNPs in a 145 seedling F1 hybrid population raised from the cross between the cultivars Sonata (♀) and Babette (♂). A linkage map containing 907 markers which spanned 1,581.5 cM across 31 linkage groups representing the 28 chromosomes of the species. Comparing the physical span of the SNP markers with the F. vesca genome sequence, the linkage groups resolved covered 79% of the estimated 830 Mb of the F. × ananassa genome. Here, we have developed the first linkage map for F. × ananassa using ddRAD and show that this technique and other related techniques are useful tools for linkage map development and downstream genetic studies in the octoploid strawberry.

  2. Effect of Linkage Disequilibrium on the Identification of Functional Variants

    Science.gov (United States)

    Thomas, Alun; Abel, Haley J; Di, Yanming; Faye, Laura L; Jin, Jing; Liu, Jin; Wu, Zheyan; Paterson, Andrew D

    2011-01-01

    We summarize the contributions of Group 9 of Genetic Analysis Workshop 17. This group addressed the problems of linkage disequilibrium and other longer range forms of allelic association when evaluating the effects of genotypes on phenotypes. Issues raised by long-range associations, whether a result of selection, stratification, possible technical errors, or chance, were less expected but proved to be important. Most contributors focused on regression methods of various types to illustrate problematic issues or to develop adaptations for dealing with high-density genotype assays. Study design was also considered, as was graphical modeling. Although no method emerged as uniformly successful, most succeeded in reducing false-positive results either by considering clusters of loci within genes or by applying smoothing metrics that required results from adjacent loci to be similar. Two unexpected results that questioned our assumptions of what is required to model linkage disequilibrium were observed. The first was that correlations between loci separated by large genetic distances can greatly inflate single-locus test statistics, and, whether the result of selection, stratification, possible technical errors, or chance, these correlations seem overabundant. The second unexpected result was that applying principal components analysis to genome-wide genotype data can apparently control not only for population structure but also for linkage disequilibrium. PMID:22128051

  3. Peroxidase profiling reveals genetic linkage between peroxidase gene clusters and basal host and non-host resistance to rusts and mildew in barley.

    Directory of Open Access Journals (Sweden)

    Ana M González

    Full Text Available BACKGROUND: Higher plants possess a large multigene family encoding secreted class III peroxidase (Prx proteins. Peroxidases appear to be associated with plant disease resistance based on observations of induction during disease challenge and the presence or absence of isozymes in resistant vs susceptible varieties. Despite these associations, there is no evidence that allelic variation of peroxidases directly determines levels of disease resistance. METHODOLOGY/PRINCIPAL FINDINGS: The current study introduces a new strategy called Prx-Profiling. We showed that with this strategy a large number of peroxidase genes can be mapped on the barley genome. In order to obtain an estimate of the total number of Prx clusters we followed a re-sampling procedure, which indicated that the barley genome contains about 40 peroxidase gene clusters. We examined the association between the Prxs mapped and the QTLs for resistance of barley to homologous and heterologous rusts, and to the barley powdery mildew fungus. We report that 61% of the QTLs for partial resistance to P. hordei, 61% of the QTLs for resistance to B. graminis and 47% of the QTLs for non-host resistance to other Puccinia species co-localize with Prx based markers. CONCLUSIONS/SIGNIFICANCE: We conclude that Prx-Profiling was effective in finding the genetic location of Prx genes on the barley genome. The finding that QTLs for basal resistance to rusts and powdery mildew fungi tend to co-locate with Prx clusters provides a base for exploring the functional role of Prx-related genes in determining natural differences in levels of basal resistance.

  4. Representing genetic variation as continuous surfaces: An approach for identifying spatial dependency in landscape genetic studies

    Science.gov (United States)

    Melanie A. Murphy; Jeffrey S. Evans; Samuel A. Cushman; Andrew Storfer

    2008-01-01

    Landscape genetics, an emerging field integrating landscape ecology and population genetics, has great potential to influence our understanding of habitat connectivity and distribution of organisms. Whereas typical population genetics studies summarize gene flow as pairwise measures between sampling localities, landscape characteristics that influence population...

  5. A genome-wide search for linkage to asthma phenotypes in the genetics of asthma international network families : evidence for a major susceptibility locus on chromosome 2p

    NARCIS (Netherlands)

    Pillai, SG; Chiano, MN; White, NJ; Speer, M; Barnes, KC; Carlsen, K; Gerritsen, Jorrit; Helms, P; Lenney, W; Silverman, M; Sly, P; Sundy, J; Tsanakas, J; von Berg, A; Whyte, M; Varsani, S; Skelding, P; Hauser, M; Vance, J; Pericak-Vance, M; Burns, DK; Middleton, LT; Brewster, [No Value; Anderson, WH; Riley, JH

    2006-01-01

    Asthma is a complex disease and the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Families with at least two siblings with asthma were collected from Europe, Australia and the US. A genome scan using a set of 364 families with a panel o

  6. A genome-wide search for linkage-disequilibrium with type 1 diabetes in a recent genetically isolated population from the Netherlands

    NARCIS (Netherlands)

    N. Vaessen (Norbert); J.J. Houwing-Duistermaat (Jeanine); T.A.M. Rademaker (Tessa); L. Testers; M.R. Batstra (Manou); L.A. Sandkuijl (Lodewijk); C.M. van Duijn (Cock); B.A. Oostra (Ben); P.J.L.M. Snijders (Pieter); P. Heutink (Peter)

    2002-01-01

    textabstractType 1 diabetes has a substantial genetic component, with consistent evidence for a susceptibility locus in the HLA-DR/DQ region (chromosome 6p) and the insulin gene region (chromosome 11p). Genome scans have identified >18 other genomic regions that may harbor putative type 1 diabetes g

  7. A genetic linkage map of black raspberry (Rubus occidentalis) and the mapping of Ag4 conferring resistance to the aphid Amphorophora agathonica

    Science.gov (United States)

    Black raspberry (Rubus occidentalis L.) is a high-value crop in the Pacific Northwest of North America with an international marketplace. Few genetic resources are readily available and little improvement has been achieved through breeding efforts to address production challenges involved in growing...

  8. Whole-genome linkage analysis in mapping alcoholism genes using single-nucleotide polymorphisms and microsatellites.

    Science.gov (United States)

    Wang, Shuang; Huang, Song; Liu, Nianjun; Chen, Liang; Oh, Cheongeun; Zhao, Hongyu

    2005-12-30

    There is currently a great interest in using single-nucleotide polymorphisms (SNPs) in genetic linkage and association studies because of the abundance of SNPs as well as the availability of high-throughput genotyping technologies. In this study, we compared the performance of whole-genome scans using SNPs with microsatellites on 143 pedigrees from the Collaborative Studies on Genetics of Alcoholism provided by Genetic Analysis Workshop 14. A total of 315 microsatellites and 10,081 SNPs from Affymetrix on 22 autosomal chromosomes were used in our analyses. We found that the results from the two scans had good overall concordance. One region on chromosome 2 and two regions on chromosome 7 showed significant linkage signals (i.e., NPL >or= 2) for alcoholism from both the SNP and microsatellite scans. The different results observed between the two scans may be explained by the difference observed in information content between the SNPs and the microsatellites.

  9. A Genetic Study on Myasthenia Gravis

    Institute of Scientific and Technical Information of China (English)

    Lu Chuan-Zhen; Zhou Zhigang; Wu Yongqin

    2000-01-01

    @@Myasthenia Gravis is considered as an autoimmune disease caused by circulating ant:bodies against acetylcholine receptor(AchR) at neuromuscular junctions. Although thousands of studies in the field of function of AchR, activation passway of immune response on MG, genetic control of o-subunit of AchR have been done in the world since 1970's, it is still unclear what is the initial factor of autoimmune response and what hind of genes control are in MG patients.

  10. Identifying Loci for the Overlap between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Using a Genome-Wide QTL Linkage Approach

    Science.gov (United States)

    Nijmeijer, Judith S.; Arias-Vasquez, Alejandro; Rommelse, Nanda N. J.; Altink, Marieke E.; Anney, Richard J. L.; Asherson, Philip; Banaschewski, Tobias; Buschgens, Cathelijne J. M.; Fliers, Ellen A.; Gill, Michael; Minderaa, Ruud B.; Poustka, Luise; Sergeant, Joseph A.; Buitelaar, Jan K.; Franke, Barbara; Ebstein, Richard P.; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sonuga-Barke, Edmund J. S.; Steinhausen, Hans-Christoph; Faraone, Stephen V.; Hartman, Catharina A.; Hoekstra, Pieter J.

    2010-01-01

    Objective: The genetic basis for autism spectrum disorder (ASD) symptoms in children with attention-deficit/hyperactivity disorder (ADHD) was addressed using a genome-wide linkage approach. Method: Participants of the International Multi-Center ADHD Genetics study comprising 1,143 probands with ADHD and 1,453 siblings were analyzed. The total and…

  11. Identifying Loci for the Overlap Between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder Using a Genome-wide QTL Linkage Approach

    NARCIS (Netherlands)

    Nijmeijer, Judith S.; Arias-Vasquez, Alejandro; Rommelse, Nanda N. J.; Altink, Marieke E.; Anney, Richard J. L.; Asherson, Philip; Banaschewski, Tobias; Buschgens, Cathelijne J. M.; Fliers, Ellen A.; Gill, Michael; Minderaa, Ruud B.; Poustka, Luise; Sergeant, Joseph A.; Buitelaar, Jan K.; Franke, Barbara; Ebstein, Richard P.; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Sonuga-Barke, Edmund J. S.; Steinhausen, Hans-Christoph; Faraone, Stephen. V.; Hartman, Catharina A.; Hoekstra, Pieter J.

    Objective: The genetic basis for autism spectrum disorder (ASD) symptoms in children with attention-deficit/hyperactivity disorder (ADHD) was addressed using a genome-wide linkage approach. Method: Participants of the International Multi-Center ADHD Genetics study comprising 1,143 probands with ADHD

  12. A linkage study between the GABAA beta2 and GABAA gamma2 subunit genes and major psychoses.

    Science.gov (United States)

    Ambrósio, Alda M; Kennedy, James L; Macciardi, Fabio; King, Nicole; Azevedo, Maria H; Oliveira, Catarina R; Pato, Carlos N

    2005-01-01

    Alterations of the gamma-aminobutyric acid (GABA) system have been implicated in the pathophysiology of major psychoses. Restriction fragment length polymorphisms associated with the human gamma-aminobutyric acid type A (GABAA) beta2 and GABAA gamma2 subunit genes on chromosome 5q32-q35 were tested to determine whether they confer susceptibility to major psychoses. Thirty-two schizophrenic families and 25 bipolar families were tested for linkage. Nonparametric linkage (NPL) analysis performed by GENEHUNTER showed no significant NPL scores for both genes in schizophrenia (GABAA beta2: NPL narrow= -0.450; NPL broad= -0.808; GABAA gamma2: NPL narrow=0.177; NPL broad= -0.051) or bipolar disorder (GABAA beta2: NPL narrow=0.834; NPL broad=0.783; GABAA gamma2: NPL narrow= -0.159; NPL broad=0.070). Linkage analysis does not support the hypothesis that variants within the GABAA beta2 and GABAA gamma2 genes are significantly linked to major psychoses in a Portuguese population.

  13. A SNP based high-density linkage map of Apis cerana reveals a high recombination rate similar to Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Yuan Yuan Shi

    Full Text Available BACKGROUND: The Eastern honey bee, Apis cerana Fabricius, is distributed in southern and eastern Asia, from India and China to Korea and Japan and southeast to the Moluccas. This species is also widely kept for honey production besides Apis mellifera. Apis cerana is also a model organism for studying social behavior, caste determination, mating biology, sexual selection, and host-parasite interactions. Few resources are available for molecular research in this species, and a linkage map was never constructed. A linkage map is a prerequisite for quantitative trait loci mapping and for analyzing genome structure. We used the Chinese honey bee, Apis cerana cerana to construct the first linkage map in the Eastern honey bee. RESULTS: F2 workers (N = 103 were genotyped for 126,990 single nucleotide polymorphisms (SNPs. After filtering low quality and those not passing the Mendel test, we obtained 3,000 SNPs, 1,535 of these were informative and used to construct a linkage map. The preliminary map contains 19 linkage groups, we then mapped the 19 linkage groups to 16 chromosomes by comparing the markers to the genome of A. mellfiera. The final map contains 16 linkage groups with a total of 1,535 markers. The total genetic distance is 3,942.7 centimorgans (cM with the largest linkage group (180 loci measuring 574.5 cM. Average marker interval for all markers across the 16 linkage groups is 2.6 cM. CONCLUSION: We constructed a high density linkage map for A. c. cerana with 1,535 markers. Because the map is based on SNP markers, it will enable easier and faster genotyping assays than randomly amplified polymorphic DNA or microsatellite based maps used in A. mellifera.

  14. A Genetic Epidemiological Study of Behavioral Traits

    NARCIS (Netherlands)

    N. Amin (Najaf)

    2011-01-01

    textabstractHuman behavioural genetics aims to unravel the genetic and environmental contributions to variations in human behaviour. Behaviour is a complex trait, involving multiple genes that are affected by a variety of other factors. Genetic epidemiological research of behaviour goes back to Sir

  15. Debating the future of genetically modified plants - bridging knowledge dimensions. A technology foresight study

    DEFF Research Database (Denmark)

    Borch, Kristian; Rasmussen, Birgitte

    2003-01-01

    to offer a coordinating method for developing and strengthening those linkages. To test this, a technological foresight study was performed on genetically modified (GM) crop technology in the Danish context. Thebackground to the study was the conflict and intense debate in Denmark over applications of gene...... technology, and especially over the deliberate release of GM crops. However, the current debate characteristically involves sharply opposed fronts. In it,stakeholders and experts on both side of the conflict advocate widely differing opinions. Without a proper, generally intelligible dialogue, the broader...... public audience finds it hard to comprehend this type of debate. The study pursues the notion thatpublic dialogue can act as a driver of future applications in the technological domain, specifically GM crops. The study concluded with a stakeholder workshop that revealed three key issues that might...

  16. Development of an integrated genome informatics, data management and workflow infrastructure: A toolbox for the study of complex disease genetics

    Directory of Open Access Journals (Sweden)

    Burren Oliver S

    2004-01-01

    Full Text Available Abstract The genetic dissection of complex disease remains a significant challenge. Sample-tracking and the recording, processing and storage of high-throughput laboratory data with public domain data, require integration of databases, genome informatics and genetic analyses in an easily updated and scaleable format. To find genes involved in multifactorial diseases such as type 1 diabetes (T1D, chromosome regions are defined based on functional candidate gene content, linkage information from humans and animal model mapping information. For each region, genomic information is extracted from Ensembl, converted and loaded into ACeDB for manual gene annotation. Homology information is examined using ACeDB tools and the gene structure verified. Manually curated genes are extracted from ACeDB and read into the feature database, which holds relevant local genomic feature data and an audit trail of laboratory investigations. Public domain information, manually curated genes, polymorphisms, primers, linkage and association analyses, with links to our genotyping database, are shown in Gbrowse. This system scales to include genetic, statistical, quality control (QC and biological data such as expression analyses of RNA or protein, all linked from a genomics integrative display. Our system is applicable to any genetic study of complex disease, of either large or small scale.

  17. Genetic variation and population substructure in outbred CD-1 mice: implications for genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Kimberly A Aldinger

    Full Text Available Outbred laboratory mouse populations are widely used in biomedical research. Since little is known about the degree of genetic variation present in these populations, they are not widely used for genetic studies. Commercially available outbred CD-1 mice are drawn from an extremely large breeding population that has accumulated many recombination events, which is desirable for genome-wide association studies. We therefore examined the degree of genome-wide variation within CD-1 mice to investigate their suitability for genetic studies. The CD-1 mouse genome displays patterns of linkage disequilibrium and heterogeneity similar to wild-caught mice. Population substructure and phenotypic differences were observed among CD-1 mice obtained from different breeding facilities. Differences in genetic variation among CD-1 mice from distinct facilities were similar to genetic differences detected between closely related human populations, consistent with a founder effect. This first large-scale genetic analysis of the outbred CD-1 mouse strain provides important considerations for the design and analysis of genetic studies in CD-1 mice.

  18. Development of gene-based markers for use in construction of the chickpea (Cicer arietinum L.) genetic linkage map and identification of QTLs associated with seed weight and plant height.

    Science.gov (United States)

    Gupta, Shefali; Kumar, Tapan; Verma, Subodh; Bharadwaj, Chellapilla; Bhatia, Sabhyata

    2015-11-01

    Seed weight and plant height are important agronomic traits and contribute to seed yield. The objective of this study was to identify QTLs underlying these traits using an intra-specific mapping population of chickpea. A F11 population of 177 recombinant inbred lines derived from a cross between SBD377 (100-seed weight--48 g and plant height--53 cm) and BGD112 (100-seed weight--15 g and plant height--65 cm) was used. A total of 367 novel EST-derived functional markers were developed which included 187 EST-SSRs, 130 potential intron polymorphisms (PIPs) and 50 expressed sequence tag polymorphisms (ESTPs). Along with these, 590 previously published markers including 385 EST-based markers and 205 genomic SSRs were utilized. Of the 957 markers tested for analysis of parental polymorphism between the two parents of the mapping population, 135 (14.64%) were found to be polymorphic. Of these, 131 polymorphic markers could be mapped to the 8 linkage groups. The linkage map had a total length of 1140.54 cM with an average marker density of 8.7 cM. The map was further used for QTL identification using composite interval mapping method (CIM). Two QTLs each for seed weight, qSW-1 and qSW-2 (explaining 11.54 and 19.24% of phenotypic variance, respectively) and plant height, qPH-1 and qPH-2 (explaining 13.98 and 12.17% of phenotypic variance, respectively) were detected. The novel set of genic markers, the intra-specific linkage map and the QTLs identified in the present study will serve as valuable genomic resources in improving the chickpea seed yield using marker-assisted selection (MAS) strategies.

  19. Influence of maternal and perinatal factors on subsequent hospitalisation for asthma in children: evidence from the Oxford record linkage study

    Directory of Open Access Journals (Sweden)

    Wotton Clare J

    2010-03-01

    Full Text Available Abstract Background There is much interest in the possibility that perinatal factors may influence the risk of disease in later life. We investigated the influence of maternal and perinatal factors on subsequent hospital admission for asthma in children. Methods Analysis of data from the Oxford record linkage study (ORLS to generate a retrospective cohort of 248 612 records of births between 1970 and 1989, with follow-up to records of subsequent hospital admission for 4 017 children with asthma up to 1999. Results Univariate analysis showed significant associations between an increased risk of admission for asthma and later years of birth (reflecting the increase in asthma in the 1970s and 1980s, low social class, asthma in the mother, unmarried mothers, maternal smoking in pregnancy, subsequent births compared with first-born, male sex, low birth weight, short gestational age, caesarean delivery, forceps delivery and not being breastfed. Multivariate analysis, identifying each risk factor that had a significant effect independently of other risk factors, confirmed associations with maternal asthma (odds ratio (OR 3.1, 95% confidence interval 2.7-3.6, male sex (versus female, 1.8, 1.7-2.0, low birth weight (1000-2999 g versus 3000-3999 g, 1.2, 1.1-1.3, maternal smoking (1.1, 1.0-1.3 and delivery by caesarean section (1.2; 1.0-1.3. In those first admitted with asthma under two years old, there were associations with having siblings (e.g. second child compared with first-born, OR 1.3, 1.0-1.7 and short gestational age (24-37 weeks versus 38-41 weeks, 1.6, 1.2-2.2. Multivariate analysis confined to those admitted with asthma aged six years or more, showed associations with maternal asthma (OR 3.8, 3.1-4.7, age of mother (under 25 versus 25-34 at birth, OR 1.16, 1.03-1.31; over 35 versus 25-34, OR 1.4, 1.1-1.7; high social class was protective (1 and 2, compared with 3, 0.72; 0.63-0.82. Hospital admission for asthma in people aged over six was more

  20. Design and analysis in genetic studies of human ageing and longevity.

    Science.gov (United States)

    Tan, Qihua; Kruse, Torben A; Christensen, Kaare

    2006-11-01

    With the success of the Human Genome Project and taking advantage of the recent developments in high-throughput genotyping techniques as well as in functional genomics, it is now feasible to collect vast quantities of genetic data with the aim of deciphering the genetics of human complex traits. As a result, the amount of research on human ageing and longevity has been growing rapidly in recent years. The situation raises questions concerning efficient choice of study population, sampling schemes, and methods of data analysis. In this article, we summarize the key issues in genetic studies of human ageing and longevity ranging from research design to statistical analyses. We discuss the virtues and drawbacks of the multidisciplinary approaches including the population-based cross-sectional and cohort studies, family-based linkage analysis, and functional genomics studies. Different analytical approaches are illustrated with their performances compared. In addition, important research topics are highlighted together with experiment design and data analyzing issues to serve as references for future studies.

  1. Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Fain, P.R.; Barker, D.F.; Chance, P.F. (Univ. of Utah, School of Medicine, Salt Lake City, UT (United States))

    1994-02-01

    Genetic linkage studies were conducted in four multigenerational families with X-linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short-tandem-repeat markers for the pericentromeric region of the X Chromosome. Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX to the pericentromeric region in each family. Multipoint analyses strongly support the order DXS337-CMTX-DXS441-(DXS56, PGK1). 38 refs., 2 figs., 1 tab.

  2. Refinement of linkage of human severe combined immunodeficiency (SCIDXI) to polymorphic markers in Xq13

    Energy Technology Data Exchange (ETDEWEB)

    Puck, J.M (Children' s Hospital of Philadelphia, PA (United States) Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)); Conely, M.E. (St. Jude Children' s Research Hospital and Univ. of Tennessee School of Medicine, Memphis (United States)); Bailey, L.C. (Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States))

    1993-07-01

    The most common form of human severe combined immunodeficiency (SCID) is inherited as an X-linked recessive genetic defect, MIM 300400. The disease locus, SCIDX1, has previously been placed in Xq13.1-q21.1 by demonstration of linkage to polymorphic markers between DXS159 and DXS3 and by exclusion from interstitial deletions of Xq21.1-q21.3. The authors report an extension of previous linkage studies, with new markers and a total of 25 SCIDX1 families including female carriers identified by nonrandom X chromosome inactivation in their T lymphocytes. SCIDX1 was nonrecombinant with DXS441, with a lod score of 17.96. Linkage relationships of new markers in the SCIDX1 families were consistent with the linkage map generated in the families of the Centre d'Etude du Polymorphisms Humain (CEPH) and with available physical map data. The most likely locus order was DXS1-(DXS159,DXS153)-DXS106-DXS132-DXS453-(SCIDX1,PGK1, DXS325,DXS347,DXS441)-DXS447-DXS72-DXYS1X-DXS3. The SCIDX1 region now spans approximately 10 Mb of DNA in Xq13; this narrowed genetic localization will assist efforts to identify gene candidates and will improve genetic management for families with SCID. 25 refs., 3 figs., 2 tabs.

  3. Genetic study of Kelp"901"strain

    Institute of Scientific and Technical Information of China (English)

    XIA Peng; WANG Xiuliang; LI Xiaojie; ZHAO Yushan; YAO Lin; DUAN Delin

    2005-01-01

    Based on DNA extraction and optimization of random amplified reaction (RAPD) to the gametophytes and sporophytes of Kelp"901"strain,genetic study on variation was conducted to its parents and offsprings of F6,F7,F8,and F9 generation.RAPD results have shown that among 30 selected primers for gametophytes,297 loci ranging from 200 to 3 000 bp were obtained in the average of 9.9 loci for each primer.This indicated a high polymorphic rate with RAPD detection.UPGMA(unweighted pair-group method arithmetic average)analysis showed that each male and female gametophyte of a generation could be clustered into one pair separately.The genetic distances of the Kelp 901 generation were 0.321 2-0.476 7,and the maximum was between F7and F8 (0.476 7).Identityanalysis showed that F6 generation was more close to the female parent(0.659 3),and F7 generation was more close to the male parent(0.578 8).To the sporophytes study in 24 selected primers for RAPD amplification,191 loci ranging from 230-2 800 bp were obtained,in the average to each primer of 8.0 loci.The heterozygosity to six populations were male parent(0.223 9),female parent(0.107 2),F6(0.216 4),F7(0.228 6),F8 (0.229 6)and F9 (0.317 2).The nearest genetic distance was 0.083 5(F8,F9).Total heterozygosity (HT)ofF6,F7,F8and F9 generations was 0.318 6,the average heterozygosity(Hs) for F6,F7,F8 and F9 generations was 0.248 0,and deduced coefficient of population differentiation (Gst) was 22.2%.Six sequence characterized amplified regions (SCAR) were preliminary screened through RAPD analysis.It needed to be verified in detail as they are significant for molecular marker assistance in breeding and selecting Laminaria.

  4. Bivariate linkage analysis of the insulin resistance syndrome phenotypes on chromosome 7q.

    Science.gov (United States)

    Lehman, Donna M; Arya, Rector; Blangero, John; Almasy, Laura; Puppala, Sobha; Dyer, Thomas D; Leach, Robin J; O'Connell, Peter; Stern, Michael P; Duggirala, Ravindranath

    2005-04-01

    Metabolic abnormalities of the insulin resistance syndrome (IRS) have been shown to aggregate in families and to exhibit trait-pair correlations, suggesting a common genetic component. A broad region on chromosome 7q has been implicated in several studies to contain loci that cosegregate with IRS-related traits. However, it is not clear whether such loci have any common genetic (pleiotropic) influences on the correlated traits. Also, it is not clear whether the chromosomal regions contain more than one locus influencing the IRS-related phenotypes. In this study we present evidence for linkage of five IRS-related traits [body mass index (BMI), waist circumference (WC), In split proinsulin (LSPI), In triglycerides (LTG), and high-density lipoprotein cholesterol (HDLC)] to a region at 7q11.23. Subsequently, to gain further insight into the genetic component(s) mapping to this region, we explored whether linkage of these traits is due to pleiotropic effects using a bivariate linkage analytical technique, which has been shown to localize susceptibility regions with precision. Four hundred forty individuals from 27 Mexican American families living in Texas were genotyped for 19 highly polymorphic markers on chromosome 7. Multipoint variance component linkage analysis was used to identify genetic location(s) influencing IRS-related traits of obesity (BMI and WC), dyslipidemia (LTG and HDLC), and insulin levels (LSPI); the analysis identified a broad chromosomal region spanning approximately 24 cM. To gain more precision in localization, we used a bivariate linkage approach for each trait pair. These analyses suggest localization of most of these bivariate traits to an approximately 6-cM region near marker D7S653 [7q11.23, 103-109 cM; a maximum bivariate LOD of 4.51 was found for the trait pair HDLC and LSPI (the LODeq score is 3.94)]. We observed evidence of pleiotropic effects in this region on obesity and insulin-related trait pairs.

  5. Molecular genetic studies in flax (Linum usitatissimum L.)

    NARCIS (Netherlands)

    Vromans, J.

    2006-01-01

    In this thesis five molecular genetic studies on flax ( Linum usitatissimum L.) are described, of which two chapters aim to characterize the genetic structure and the amount of genetic diversity in the primary and secondary gene pool of the crop species. Three chapters describe the development of

  6. Genetic study of hyperkalemic periodic paralysis in horses.

    Science.gov (United States)

    Spier, S J; Carlson, G P; Harrold, D; Bowling, A; Byrns, G; Bernoco, D

    1993-03-15

    Four Quarter Horses (1 stallion, 3 mares) with hyperkalemic periodic paralysis were mated to unaffected horses to determine the genetic basis of the disease. The affected stallion was bred to 11 unaffected mares (4 Quarter Horses, 1 Arabian, 2 Standardbreds, and 4 Thoroughbreds). The 3 affected mares were bred to an unaffected Quarter Horse stallion. Of the 15 offspring obtained from these matings, 9 were affected with hyperkalemic periodic paralysis, and 6 were unaffected, consistent with an autosomal dominant mode of inheritance. Diagnosis was established by results of oral administration of potassium chloride and demonstration of characteristic clinical signs accompanied by hyperkalemia. Oral administration of potassium chloride resulted in marked increases in plasma potassium concentrations in affected and unaffected foals, although hyperkalemia was associated with clinical signs of hyperkalemic periodic paralysis in the affected foals. Evaluation of blood samples from affected and unaffected offspring revealed no linkage with erythrocyte and serum markers at 24 loci.

  7. Adsorption of small molecules on the [Zn-Zn]2+ linkage in zeolite. A DFT study of ferrierite

    Science.gov (United States)

    Benco, Lubomir

    2017-02-01

    In zeolites monovalent Zn(I) forms a sub-nano particles [Zn-Zn]2+ stabilized in rings of the zeolite framework, which exhibit interesting catalytic properties. This work reports on adsorption properties of [Zn-Zn]2+ particles in zeolite ferrierite investigated for a set of probing diatomic (N2, O2, H2, CO, NO) and triatomic (CO2, N2O, NO2, H2O) molecules using dispersion-corrected DFT. Three [Zn-Zn]2+ sites are compared differing in the location and stability. On all sites molecules form physisorbed clusters with the molecule connected on-top of the Zn-Zn linkage. In physisorbed clusters adsorption induces only slight change of bonding and the geometry of the Zn-Zn linkage. Some molecules can form stable chemisorbed clusters in which the molecule is integrated between two Zn+ cations. The sandwich-like chemisorption causes pronounced changes of bonding and can lead to the transfer of the electron density between two Zn+ cations and to a change of the oxidation state. The knowledge of bonding of small molecules can help understanding of the mechanism of conversion reactions catalyzed by sub-nano [Zn-Zn] particles.

  8. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  9. Dissecting the Genetics of Stroke

    OpenAIRE

    Rijn, Marie Josee

    2007-01-01

    textabstractStroke is a leading cause of death and disability in the Western world. It is a complex disease resulting from environmental factors and genetic factors, as well as gene-gene and geneenvironment interactions. Many studies have attempted to unravel the genetic aetiology of stroke, but results have been inconsistent. Most have used the candidate gene approach, but genome-wide linkage analyses have also been performed. Recently, results of genome-wide association studies have been re...

  10. Interactive Record Linkage

    Directory of Open Access Journals (Sweden)

    2000-12-01

    Full Text Available In order to carry out demographic analyses at individual and group levels, a manual method of linking individual event records from parish registers was developed in the late 1950s. In order to save time and to work with larger areas than small parishes, systems for automatic record linkage were developed a couple of decades later. A third method, an interactive record linkage, named Demolink, has been developed even more recently. The main new feature of the method is the possibility of linking from more than two historical sources simultaneously. This improves the process of sorting out which events belong to which individual life courses. This paper discusses how Demolink was used for record linkage in a large Norwegian parish for the period 1801-1878.

  11. Integrating empirical data and population genetic simulations to study the genetic architecture of type 2 diabetes

    OpenAIRE

    Agarwala, Vineeta

    2013-01-01

    Most common diseases have substantial heritable components but are characterized by complex inheritance patterns implicating numerous genetic and environmental factors. A longstanding goal of human genetics research is to delineate the genetic architecture of these traits - the number, frequencies, and effect sizes of disease-causing alleles - to inform mapping studies, elucidate mechanisms of disease, and guide development of targeted clinical therapies and diagnostics. Although vast empir...

  12. Construction of high-quality recombination maps with low-coverage genomic sequencing for joint linkage analysis in maize

    Science.gov (United States)

    A genome-wide association study (GWAS) is the foremost strategy used for finding genes that control human diseases and agriculturally important traits, but it often reports false positives. In contrast, its complementary method, linkage analysis, provides direct genetic confirmation, but with limite...

  13. HIV-1 transmission linkage in an HIV-1 prevention clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Leitner, Thomas [Los Alamos National Laboratory; Campbell, Mary S [UNIV OF WASHINGTON; Mullins, James I [UNIV OF WASHINGTON; Hughes, James P [UNIV OF WASHINGTON; Wong, Kim G [UNIV OF WASHINGTON; Raugi, Dana N [UNIV OF WASHINGTON; Scrensen, Stefanie [UNIV OF WASHINGTON

    2009-01-01

    HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

  14. Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families.

    Science.gov (United States)

    Woodbury-Smith, M; Bilder, D A; Morgan, J; Jerominski, L; Darlington, T; Dyer, T; Paterson, A D; Coon, H

    2017-01-01

    It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p = 1.72E-07). Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific langua