A new method of linkage analysis using LOD scores for quantitative traits supports linkage of monoamine oxidase activity to D17S250 in the Collaborative Study on the Genetics of Alcoholism pedigrees.

PubMed

Curtis, David; Knight, Jo; Sham, Pak C

2005-09-01

Although LOD score methods have been applied to diseases with complex modes of inheritance, linkage analysis of quantitative traits has tended to rely on non-parametric methods based on regression or variance components analysis. Here, we describe a new method for LOD score analysis of quantitative traits which does not require specification of a mode of inheritance. The technique is derived from the MFLINK method for dichotomous traits. A range of plausible transmission models is constructed, constrained to yield the correct population mean and variance for the trait but differing with respect to the contribution to the variance due to the locus under consideration. Maximized LOD scores under homogeneity and admixture are calculated, as is a model-free LOD score which compares the maximized likelihoods under admixture assuming linkage and no linkage. These LOD scores have known asymptotic distributions and hence can be used to provide a statistical test for linkage. The method has been implemented in a program called QMFLINK. It was applied to data sets simulated using a variety of transmission models and to a measure of monoamine oxidase activity in 105 pedigrees from the Collaborative Study on the Genetics of Alcoholism. With the simulated data, the results showed that the new method could detect linkage well if the true allele frequency for the trait was close to that specified. However, it performed poorly on models in which the true allele frequency was much rarer. For the Collaborative Study on the Genetics of Alcoholism data set only a modest overlap was observed between the results obtained from the new method and those obtained when the same data were analysed previously using regression and variance components analysis. Of interest is that D17S250 produced a maximized LOD score under homogeneity and admixture of 2.6 but did not indicate linkage using the previous methods. However, this region did produce evidence for linkage in a separate data set, suggesting that QMFLINK may have been able to detect a true linkage which was not picked up by the other methods. The application of model-free LOD score analysis to quantitative traits is novel and deserves further evaluation of its merits and disadvantages relative to other methods.

A power study of bivariate LOD score analysis of a complex trait and fear/discomfort with strangers

PubMed Central

Ji, Fei; Lee, Dayoung; Mendell, Nancy Role

2005-01-01

Complex diseases are often reported along with disease-related traits (DRT). Sometimes investigators consider both disease and DRT phenotypes separately and sometimes they consider individuals as affected if they have either the disease or the DRT, or both. We propose instead to consider the joint distribution of the disease and the DRT and do a linkage analysis assuming a pleiotropic model. We evaluated our results through analysis of the simulated datasets provided by Genetic Analysis Workshop 14. We first conducted univariate linkage analysis of the simulated disease, Kofendrerd Personality Disorder and one of its simulated associated traits, phenotype b (fear/discomfort with strangers). Subsequently, we considered the bivariate phenotype, which combined the information on Kofendrerd Personality Disorder and fear/discomfort with strangers. We developed a program to perform bivariate linkage analysis using an extension to the Elston-Stewart peeling method of likelihood calculation. Using this program we considered the microsatellites within 30 cM of the gene pleiotropic for this simulated disease and DRT. Based on 100 simulations of 300 families we observed excellent power to detect linkage within 10 cM of the disease locus using the DRT and the bivariate trait. PMID:16451570

A power study of bivariate LOD score analysis of a complex trait and fear/discomfort with strangers.

PubMed

Ji, Fei; Lee, Dayoung; Mendell, Nancy Role

2005-12-30

Complex diseases are often reported along with disease-related traits (DRT). Sometimes investigators consider both disease and DRT phenotypes separately and sometimes they consider individuals as affected if they have either the disease or the DRT, or both. We propose instead to consider the joint distribution of the disease and the DRT and do a linkage analysis assuming a pleiotropic model. We evaluated our results through analysis of the simulated datasets provided by Genetic Analysis Workshop 14. We first conducted univariate linkage analysis of the simulated disease, Kofendrerd Personality Disorder and one of its simulated associated traits, phenotype b (fear/discomfort with strangers). Subsequently, we considered the bivariate phenotype, which combined the information on Kofendrerd Personality Disorder and fear/discomfort with strangers. We developed a program to perform bivariate linkage analysis using an extension to the Elston-Stewart peeling method of likelihood calculation. Using this program we considered the microsatellites within 30 cM of the gene pleiotropic for this simulated disease and DRT. Based on 100 simulations of 300 families we observed excellent power to detect linkage within 10 cM of the disease locus using the DRT and the bivariate trait.

Saturation of an Intra-Gene Pool Linkage Map: Towards a Unified Consensus Linkage Map for Fine Mapping and Synteny Analysis in Common Bean

PubMed Central

Galeano, Carlos H.; Fernandez, Andrea C.; Franco-Herrera, Natalia; Cichy, Karen A.; McClean, Phillip E.; Vanderleyden, Jos; Blair, Matthew W.

2011-01-01

Map-based cloning and fine mapping to find genes of interest and marker assisted selection (MAS) requires good genetic maps with reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers including SSR, SNP, and gene-based markers. On average the polymorphism rate was 7.7% due to the narrow genetic base between the parents. The DB linkage map consisted of 291 markers with a total map length of 1,788 cM. A consensus map was built using the core mapping populations derived from inter-gene pool crosses: DOR364×G19833 (DG) and BAT93×JALO EEP558 (BJ). The consensus map consisted of a total of 1,010 markers mapped, with a total map length of 2,041 cM across 11 linkage groups. On average, each linkage group on the consensus map contained 91 markers of which 83% were single copy markers. Finally, a synteny analysis was carried out using our highly saturated consensus maps compared with the soybean pseudo-chromosome assembly. A total of 772 marker sequences were compared with the soybean genome. A total of 44 syntenic blocks were identified. The linkage group Pv6 presented the most diverse pattern of synteny with seven syntenic blocks, and Pv9 showed the most consistent relations with soybean with just two syntenic blocks. Additionally, a co-linear analysis using common bean transcript map information against soybean coding sequences (CDS) revealed the relationship with 787 soybean genes. The common bean consensus map has allowed us to map a larger number of markers, to obtain a more complete coverage of the common bean genome. Our results, combined with synteny relationships provide tools to increase marker density in selected genomic regions to identify closely linked polymorphic markers for indirect selection, fine mapping or for positional cloning. PMID:22174773

Data cleaning and management protocols for linked perinatal research data: a good practice example from the Smoking MUMS (Maternal Use of Medications and Safety) Study.

PubMed

Tran, Duong Thuy; Havard, Alys; Jorm, Louisa R

2017-07-11

Data cleaning is an important quality assurance in data linkage research studies. This paper presents the data cleaning and preparation process for a large-scale cross-jurisdictional Australian study (the Smoking MUMS Study) to evaluate the utilisation and safety of smoking cessation pharmacotherapies during pregnancy. Perinatal records for all deliveries (2003-2012) in the States of New South Wales (NSW) and Western Australia were linked to State-based data collections including hospital separation, emergency department and death data (mothers and babies) and congenital defect notifications (babies in NSW) by State-based data linkage units. A national data linkage unit linked pharmaceutical dispensing data for the mothers. All linkages were probabilistic. Twenty two steps assessed the uniqueness of records and consistency of items within and across data sources, resolved discrepancies in the linkages between units, and identified women having records in both States. State-based linkages yielded a cohort of 783,471 mothers and 1,232,440 babies. Likely false positive links relating to 3703 mothers were identified. Corrections of baby's date of birth and age, and parity were made for 43,578 records while 1996 records were flagged as duplicates. Checks for the uniqueness of the matches between State and national linkages detected 3404 ID clusters, suggestive of missed links in the State linkages, and identified 1986 women who had records in both States. Analysis of content data can identify inaccurate links that cannot be detected by data linkage units that have access to personal identifiers only. Perinatal researchers are encouraged to adopt the methods presented to ensure quality and consistency among studies using linked administrative data.

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

PubMed Central

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

2013-01-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sander, A.; Schmelzle, R.; Murray, J.C.

1995-01-01

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

Genome survey and high-density genetic map construction provide genomic and genetic resources for the Pacific White Shrimp Litopenaeus vannamei

PubMed Central

Yu, Yang; Zhang, Xiaojun; Yuan, Jianbo; Li, Fuhua; Chen, Xiaohan; Zhao, Yongzhen; Huang, Long; Zheng, Hongkun; Xiang, Jianhai

2015-01-01

The Pacific white shrimp Litopenaeus vannamei is the dominant crustacean species in global seafood mariculture. Understanding the genome and genetic architecture is useful for deciphering complex traits and accelerating the breeding program in shrimp. In this study, a genome survey was conducted and a high-density linkage map was constructed using a next-generation sequencing approach. The genome survey was used to identify preliminary genome characteristics and to generate a rough reference for linkage map construction. De novo SNP discovery resulted in 25,140 polymorphic markers. A total of 6,359 high-quality markers were selected for linkage map construction based on marker coverage among individuals and read depths. For the linkage map, a total of 6,146 markers spanning 4,271.43 cM were mapped to 44 sex-averaged linkage groups, with an average marker distance of 0.7 cM. An integration analysis linked 5,885 genome scaffolds and 1,504 BAC clones to the linkage map. Based on the high-density linkage map, several QTLs for body weight and body length were detected. This high-density genetic linkage map reveals basic genomic architecture and will be useful for comparative genomics research, genome assembly and genetic improvement of L. vannamei and other penaeid shrimp species. PMID:26503227

Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

PubMed Central

Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.

2012-01-01

A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797

PrePhyloPro: phylogenetic profile-based prediction of whole proteome linkages

PubMed Central

Niu, Yulong; Liu, Chengcheng; Moghimyfiroozabad, Shayan; Yang, Yi

2017-01-01

Direct and indirect functional links between proteins as well as their interactions as part of larger protein complexes or common signaling pathways may be predicted by analyzing the correlation of their evolutionary patterns. Based on phylogenetic profiling, here we present a highly scalable and time-efficient computational framework for predicting linkages within the whole human proteome. We have validated this method through analysis of 3,697 human pathways and molecular complexes and a comparison of our results with the prediction outcomes of previously published co-occurrency model-based and normalization methods. Here we also introduce PrePhyloPro, a web-based software that uses our method for accurately predicting proteome-wide linkages. We present data on interactions of human mitochondrial proteins, verifying the performance of this software. PrePhyloPro is freely available at http://prephylopro.org/phyloprofile/. PMID:28875072

Quantifying landscape linkages among giant panda subpopulations in regional scale conservation.

PubMed

Qi, Dunwu; Hu, Yibo; Gu, Xiaodong; Yang, Xuyi; Yang, Guang; Wei, Fuwen

2012-06-01

Understanding habitat requirements and identifying landscape linkages are essential for the survival of isolated populations of endangered species. Currently, some of the giant panda populations are isolated, which threatens their long-term survival, particularly in the Xiaoxiangling mountains. In the present study, we quantified niche requirements and then identified potential linkages of giant panda subpopulations in the most isolated region, using ecological niche factor analysis and a least-cost path model. Giant pandas preferred habitat with conifer forest and gentle slopes (>20 to ≤30°). Based on spatial distribution of suitable habitat, linkages were identified for the Yele subpopulation to 4 other subpopulations (Liziping, Matou, Xinmin and Wanba). Their lengths ranged from 15 to 54 km. The accumulated cost ranged from 693 to 3166 and conifer forest covered over 31%. However, a variety of features (e.g. major roads, human settlements and large unforested areas) might act as barriers along the linkages for giant panda dispersal. Our analysis quantified giant panda subpopulation connectivity to ensure long-term survival. © 2012 ISZS, Blackwell Publishing and IOZ/CAS.

Significant Linkage for Tourette Syndrome in a Large French Canadian Family

PubMed Central

Mérette, Chantal; Brassard, Andrée; Potvin, Anne; Bouvier, Hélène; Rousseau, François; Émond, Claudia; Bissonnette, Luc; Roy, Marc-André; Maziade, Michel; Ott, Jurg; Caron, Chantal

2000-01-01

Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS. PMID:10986045

Neuropsychological Endophenotype Approach to Genome-wide Linkage Analysis Identifies Susceptibility Loci for ADHD on 2q21.1 and 13q12.11

PubMed Central

Rommelse, Nanda N.J.; Arias-Vásquez, Alejandro; Altink, Marieke E.; Buschgens, Cathelijne J.M.; Fliers, Ellen; Asherson, Philip; Faraone, Stephen V.; Buitelaar, Jan K.; Sergeant, Joseph A.; Oosterlaan, Jaap; Franke, Barbara

2008-01-01

ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study comprising 238 DSM-IV combined-type ADHD probands and their 112 affected and 195 nonaffected siblings. Eight candidate neuropsychological ADHD endophenotypes with heritabilities > 0.2 were used as quantitative traits. In addition, an overall component score of neuropsychological functioning was used. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses. Two significant genome-wide linkage signals were found, one for Motor Timing on chromosome 2q21.1 (LOD score: 3.944) and one for Digit Span on 13q12.11 (LOD score: 3.959). Ten suggestive linkage signals were found (LOD scores ≥ 2) on chromosomes 2p, 2q, 3p, 4q, 8q, 12p, 12q, 14q, and 17q. The suggestive linkage signal for the component score that was found at 2q14.3 (LOD score: 2.878) overlapped with the region significantly linked to Motor Timing. Endophenotype approaches may increase power to detect susceptibility loci in ADHD and possibly in other complex disorders. PMID:18599010

Improving estimates of genetic maps: a meta-analysis-based approach.

PubMed

Stewart, William C L

2007-07-01

Inaccurate genetic (or linkage) maps can reduce the power to detect linkage, increase type I error, and distort haplotype and relationship inference. To improve the accuracy of existing maps, I propose a meta-analysis-based method that combines independent map estimates into a single estimate of the linkage map. The method uses the variance of each independent map estimate to combine them efficiently, whether the map estimates use the same set of markers or not. As compared with a joint analysis of the pooled genotype data, the proposed method is attractive for three reasons: (1) it has comparable efficiency to the maximum likelihood map estimate when the pooled data are homogeneous; (2) relative to existing map estimation methods, it can have increased efficiency when the pooled data are heterogeneous; and (3) it avoids the practical difficulties of pooling human subjects data. On the basis of simulated data modeled after two real data sets, the proposed method can reduce the sampling variation of linkage maps commonly used in whole-genome linkage scans. Furthermore, when the independent map estimates are also maximum likelihood estimates, the proposed method performs as well as or better than when they are estimated by the program CRIMAP. Since variance estimates of maps may not always be available, I demonstrate the feasibility of three different variance estimators. Overall, the method should prove useful to investigators who need map positions for markers not contained in publicly available maps, and to those who wish to minimize the negative effects of inaccurate maps. Copyright 2007 Wiley-Liss, Inc.

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

PubMed Central

2010-01-01

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, respectively. These distorted loci tended to cluster on LG1, LG3, LG4 and LG5. There were only 15 EST-SSR markers mapped due to low polymorphism. By comparison, there were potential synteny, collinear order of some markers and conservation of collinear linkage groups among the maps and with the AA genome but not fully conservative. Conclusion A composite linkage map was constructed from three individual mapping populations with 175 SSR markers in 22 composite linkage groups. This composite genetic linkage map is among the first "true" tetraploid peanut maps produced. This map also consists of 47 SSRs that have been used in the published AA genome maps, and could be used in comparative mapping studies. The primers described in this study are PCR-based markers, which are easy to share for genetic mapping in peanuts. All 1044 primer pairs are provided as additional files and the three RIL populations will be made available to public upon request for quantitative trait loci (QTL) analysis and linkage map improvement. PMID:20105299

Factors associated with linkage to HIV care and TB treatment at community-based HIV testing services in Cape Town, South Africa.

PubMed

Meehan, Sue-Ann; Sloot, Rosa; Draper, Heather R; Naidoo, Pren; Burger, Ronelle; Beyers, Nulda

2018-01-01

Diagnosing HIV and/or TB is not sufficient; linkage to care and treatment is conditional to reduce the burden of disease. This study aimed to determine factors associated with linkage to HIV care and TB treatment at community-based services in Cape Town, South Africa. This retrospective cohort study utilized routinely collected data from clients who utilized stand-alone (fixed site not attached to a health facility) and mobile HIV testing services in eight communities in the City of Cape Town Metropolitan district, between January 2008 and June 2012. Clients were included in the analysis if they were ≥12 years and had a known HIV status. Generalized estimating equations (GEE) logistic regression models were used to assess the association between determinants (sex, age, HIV testing service and co-infection status) and self-reported linkage to HIV care and/or TB treatment. Linkage to HIV care was 3 738/5 929 (63.1%). Linkage to HIV care was associated with the type of HIV testing service. Clients diagnosed with HIV at mobile services had a significantly reduced odds of linking to HIV care (aOR 0.7 (CI 95%: 0.6-0.8), p<0.001. Linkage to TB treatment was 210/275 (76.4%). Linkage to TB treatment was not associated with sex and service type, but was associated with age. Clients in older age groups were less likely to link to TB treatment compared to clients in the age group 12-24 years (all, p-value<0.05). A large proportion of clients diagnosed with HIV at mobile services did not link to care. Almost a quarter of clients diagnosed with TB did not link to treatment. Integrated community-based HIV and TB testing services are efficient in diagnosing HIV and TB, but strategies to improve linkage to care are required to control these epidemics.

Allele-sharing models: LOD scores and accurate linkage tests.

PubMed

Kong, A; Cox, N J

1997-11-01

Starting with a test statistic for linkage analysis based on allele sharing, we propose an associated one-parameter model. Under general missing-data patterns, this model allows exact calculation of likelihood ratios and LOD scores and has been implemented by a simple modification of existing software. Most important, accurate linkage tests can be performed. Using an example, we show that some previously suggested approaches to handling less than perfectly informative data can be unacceptably conservative. Situations in which this model may not perform well are discussed, and an alternative model that requires additional computations is suggested.

Allele-sharing models: LOD scores and accurate linkage tests.

PubMed Central

Kong, A; Cox, N J

1997-01-01

Starting with a test statistic for linkage analysis based on allele sharing, we propose an associated one-parameter model. Under general missing-data patterns, this model allows exact calculation of likelihood ratios and LOD scores and has been implemented by a simple modification of existing software. Most important, accurate linkage tests can be performed. Using an example, we show that some previously suggested approaches to handling less than perfectly informative data can be unacceptably conservative. Situations in which this model may not perform well are discussed, and an alternative model that requires additional computations is suggested. PMID:9345087

A linkage and family-based association analysis of a potential neurocognitive endophenotype of bipolar disorder.

PubMed

Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

2007-01-01

The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance characterized by genetic and phenotypic heterogeneity, genetic epistasis, and gene-environment interactions. In this paper two strategies were used to ameliorate these confounding factors. A unique South African sample including 190 individuals of the relatively, reproductively isolated Afrikaner population was assessed with a battery of neuropsychological tests in an attempt to identify a BPD-associated quantitative trait or endophenotype. BPD individuals performed significantly worse than their unaffected relatives on visual and verbal memory tasks, a finding congruent with the literature. Afocused linkage and family-based association study was carried out using this memory-related endophenotype. In the largest 77-strong Afrikaner pedigree significant evidence for linkage was detected on chromosome 22q11, a region previously implicated in BPD. The quantitative transmission disequilibrium tests-based association analysis suggested that functional variants of the DRD4 and MAO-A genes modulate memory-related cognition. We speculate that polymorphisms at these loci may predispose to a subtype of BPD characterized by memory-related deficits.

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

PubMed Central

Simpson, Claire L; Cropp, Cheryl D; Wahlfors, Tiina; George, Asha; Jones, MaryPat S; Harper, Ursula; Ponciano-Jackson, Damaris; Tammela, Teuvo; Schleutker, Johanna; Bailey-Wilson, Joan E

2013-01-01

Prostate cancer (PrCa) is the most common male cancer in developed countries and the second most common cause of cancer death after lung cancer. We recently reported a genome-wide linkage scan in 69 Finnish hereditary PrCa (HPC) families, which replicated the HPC9 locus on 17q21-q22 and identified a locus on 2q37. The aim of this study was to identify and to detect other loci linked to HPC. Here we used ordered subset analysis (OSA), conditioned on nonparametric linkage to these loci to detect other loci linked to HPC in subsets of families, but not the overall sample. We analyzed the families based on their evidence for linkage to chromosome 2, chromosome 17 and a maximum score using the strongest evidence of linkage from either of the two loci. Significant linkage to a 5-cM linkage interval with a peak OSA nonparametric allele-sharing LOD score of 4.876 on Xq26.3-q27 (ΔLOD=3.193, empirical P=0.009) was observed in a subset of 41 families weakly linked to 2q37, overlapping the HPCX1 locus. Two peaks that were novel to the analysis combining linkage evidence from both primary loci were identified; 18q12.1-q12.2 (OSA LOD=2.541, ΔLOD=1.651, P=0.03) and 22q11.1-q11.21 (OSA LOD=2.395, ΔLOD=2.36, P=0.006), which is close to HPC6. Using OSA allows us to find additional loci linked to HPC in subsets of families, and underlines the complex genetic heterogeneity of HPC even in highly aggregated families. PMID:22948022

Combined linkage and association analyses identify a novel locus for obesity near PROX1 in Asians.

PubMed

Kim, Hyun-Jin; Yoo, Yun Joo; Ju, Young Seok; Lee, Seungbok; Cho, Sung-Il; Sung, Joohon; Kim, Jong-Il; Seo, Jeong-Sun

2013-11-01

Although genome-wide association studies (GWAS) have substantially contributed to understanding the genetic architecture, unidentified variants for complex traits remain an issue. One of the efficient approaches is the improvement of the power of GWAS scan by weighting P values with prior linkage signals. Our objective was to identify the novel candidates for obesity in Asian populations by using genemapping strategies that combine linkage and association analyses. To obtain linkage information for body mass index (BMI) and waist circumference (WC), we performed a multipoint genome-wide linkage study in an isolated Mongolian sample of 1,049 individuals from 74 families. Next, a family-based GWAS, which integrates within- and between-family components, was performed using the genotype data of 756 individuals of the Mongolian sample, and P values for association were weighted using linkage information obtained previously. For both BMI (LOD = 3.3) and WC (LOD = 2.6), the highest linkage peak was discovered at chromosome 10q11.22. In family-based GWAS combined with linkage information, six single-nucleotide polymorphisms (SNPs) for BMI and five SNPs for WC reached a significant level of association (linkage weighted P < 1 × 10(-5) ). Of these, only one of the SNPs associated with WC (rs1704198) was replicated in 327 Korean families comprising 1,301 individuals. This SNP was located in the proximity of the prosperorelated homeobox 1 (PROX1) gene, the function of which was validated previously in a mouse model. Our powerful strategic analysis enabled the discovery of a novel candidate gene, PROX1, associated with WC in an Asian population. Copyright © 2012 The Obesity Society.

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

PubMed Central

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

2016-01-01

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. PMID:27162496

Linkage analysis with multiplexed short tandem repeat polymorphisms using infrared fluorescence and M13 tailed primers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oetting, W.S.; Lee, H.K.; Flanders, D.J.

The use of short tandem repeat polymorphisms (STRPs) as marker loci for linkage analysis is becoming increasingly important due to their large numbers in the human genome and their high degree of polymorphism. Fluorescence-based detection of the STRP pattern with an automated DNA sequencer has improved the efficiency of this technique by eliminating the need for radioactivity and producing a digitized autoradiogram-like image that can be used for computer analysis. In an effort to simplify the procedure and to reduce the cost of fluorescence STRP analysis, we have developed a technique known as multiplexing STRPs with tailed primers (MSTP) usingmore » primers that have a 19-bp extension, identical to the sequence of an M13 sequencing primer, on the 5{prime} end of the forward primer in conjunction with multiplexing several primer pairs in a single polymerase chain reaction (PCR) amplification. The banding pattern is detected with the addition of the M13 primer-dye conjugate as the sole primer conjugated to the fluorescent dye, eliminating the need for direct conjugation of the infrared fluorescent dye to the STRP primers. The use of MSTP for linkage analysis greatly reduces the number of PCR reactions. Up to five primer pairs can be multiplexed together in the same reaction. At present, a set of 148 STRP markers spaced at an average genetic distance of 28 cM throughout the autosomal genome can be analyzed in 37 sets of multiplexed amplification reactions. We have automated the analysis of these patterns for linkage using software that both detects the STRP banding pattern and determines their sizes. This information can then be exported in a user-defined format from a database manager for linkage analysis. 15 refs., 2 figs., 4 tabs.« less

Identification of Sex-determining Loci in Pacific White Shrimp Litopeneaus vannamei Using Linkage and Association Analysis.

PubMed

Yu, Yang; Zhang, Xiaojun; Yuan, Jianbo; Wang, Quanchao; Li, Shihao; Huang, Hao; Li, Fuhua; Xiang, Jianhai

2017-06-01

The Pacific white shrimp Litopenaeus vannamei is a predominant aquaculture shrimp species in the world. Like other animals, the L. vannamei exhibited sexual dimorphism in growth trait. Mapping of the sex-determining locus will be very helpful to clarify the sex determination system and further benefit the shrimp aquaculture industry towards the production of mono-sex stocks. Based on the data used for high-density linkage map construction, linkage-mapping analysis was conducted. The sex determination region was mapped in linkage group (LG) 18. A large region from 0 to 21.205 cM in LG18 showed significant association with sex. However, none of the markers in this region showed complete association with sex in the other populations. So an association analysis was designed using the female parent, pool of female progenies, male parent, and pool of male progenies. Markers were de novo developed and those showing significant differences between female and male pools were identified. Among them, three sex-associated markers including one fully associated marker were identified. Integration of linkage and association analysis showed that the sex determination region was fine-mapped in a small region along LG18. The identified sex-associated marker can be used for the sex detection of this species at genetic level. The fine-mapped sex-determining region will contribute to the mapping of sex-determining gene and help to clarify sex determination system for L. vannamei.

A Genomewide Linkage Scan of Cocaine Dependence and Major Depressive Episode in Two Populations

PubMed Central

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R; Farrer, Lindsay A; Gelernter, Joel

2011-01-01

Cocaine dependence (CD) and major depressive episode (MDE) frequently co-occur with poorer treatment outcome and higher relapse risk. Shared genetic risk was affirmed; to date, there have been no reports of genomewide linkage scans (GWLSs) surveying the susceptibility regions for comorbid CD and MDE (CD–MDE). We aimed to identify chromosomal regions and candidate genes susceptible to CD, MDE, and CD–MDE in African Americans (AAs) and European Americans (EAs). A total of 1896 individuals were recruited from 384 AA and 355 EA families, each with at least a sibling-pair with CD and/or opioid dependence. Array-based genotyping of about 6000 single-nucleotide polymorphisms was completed for all individuals. Parametric and non-parametric genomewide linkage analyses were performed. We found a genomewide-significant linkage peak on chromosome 7 at 183.4 cM for non-parametric analysis of CD–MDE in AAs (lod=3.8, genomewide empirical p=0.016; point-wise p=0.00001). A nearly genomewide significant linkage was identified for CD–MDE in EAs on chromosome 5 at 14.3 cM (logarithm of odds (lod)=2.95, genomewide empirical p=0.055; point-wise p=0.00012). Parametric analysis corroborated the findings in these two regions and improved the support for the peak on chromosome 5 so that it reached genomewide significance (heterogeneity lod=3.28, genomewide empirical p=0.046; point-wise p=0.00053). This is the first GWLS for CD–MDE. The genomewide significant linkage regions on chromosomes 5 and 7 harbor four particularly promising candidate genes: SRD5A1, UBE3C, PTPRN2, and VIPR2. Replication of the linkage findings in other populations is warranted, as is a focused analysis of the genes located in the linkage regions implicated here. PMID:21849985

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stein, J.D.; Nelson, L.D.; Conner, B.J.

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,more » 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.« less

Motor sequencing deficit as an endophenotype of speech sound disorder: a genome-wide linkage analysis in a multigenerational family.

PubMed

Peter, Beate; Matsushita, Mark; Raskind, Wendy H

2012-10-01

The aim of this pilot study was to investigate a measure of motor sequencing deficit as a potential endophenotype of speech sound disorder (SSD) in a multigenerational family with evidence of familial SSD. In a multigenerational family with evidence of a familial motor-based SSD, affectation status and a measure of motor sequencing during oral motor testing were obtained. To further investigate the role of motor sequencing as an endophenotype for genetic studies, parametric and nonparametric linkage analyses were carried out using a genome-wide panel of 404 microsatellites. In seven of the 10 family members with available data, SSD affectation status and motor sequencing status coincided. Linkage analysis revealed four regions of interest, 6p21, 7q32, 7q36, and 8q24, primarily identified with the measure of motor sequencing ability. The 6p21 region overlaps with a locus implicated in rapid alternating naming in a recent genome-wide dyslexia linkage study. The 7q32 locus contains a locus implicated in dyslexia. The 7q36 locus borders on a gene known to affect the component traits of language impairment. The results are consistent with a motor-based endophenotype of SSD that would be informative for genetic studies. The linkage results in this first genome-wide study in a multigenerational family with SSD warrant follow-up in additional families and with fine mapping or next-generation approaches to gene identification.

Motor sequencing deficit as an endophenotype of speech sound disorder: A genome-wide linkage analysis in a multigenerational family

PubMed Central

Peter, Beate; Matsushita, Mark; Raskind, Wendy H.

2012-01-01

Objectives The purpose of this pilot study was to investigate a measure of motor sequencing deficit as a potential endophenotype of speech sound disorder (SSD) in a multigenerational family with evidence of familial SSD. Methods In a multigenerational family with evidence of a familial motor-based SSD, affectation status and a measure of motor sequencing during oral motor testing were obtained. To further investigate the role of motor sequencing as an endophenotype for genetic studies, parametric and nonparametric linkage analyses were conducted using a genome-wide panel of 404 microsatellites. Results In seven of the ten family members with available data, SSD affectation status and motor sequencing status coincided. Linkage analysis revealed four regions of interest, 6p21, 7q32, 7q36, and 8q24, primarily identified with the measure of motor sequencing ability. The 6p21 region overlaps with a locus implicated in rapid alternating naming in a recent genome-wide dyslexia linkage study. The 7q32 locus contains a locus implicated in dyslexia. The 7q36 locus borders on a gene known to affect component traits of language impairment. Conclusions Results are consistent with a motor-based endophenotype of SSD that would be informative for genetic studies. The linkage results in this first genome-wide study in a multigenerational family with SSD warrant follow-up in additional families and with fine mapping or next-generation approaches to gene identification. PMID:22517379

Economic Modeling and Analysis of Educational Vouchers

ERIC Educational Resources Information Center

Epple, Dennis; Romano, Richard

2012-01-01

The analysis of educational vouchers has evolved from market-based analogies to models that incorporate distinctive features of the educational environment. These distinctive features include peer effects, scope for private school pricing and admissions based on student characteristics, the linkage of household residential and school choices in…

Nance-Horan syndrome: linkage analysis in a family from The Netherlands.

PubMed

Bergen, A A; ten Brink, J; Schuurman, E J; Bleeker-Wagemakers, E M

1994-05-01

Linkage analysis was carried out in a Dutch family with Nance-Horan (NH) syndrome. Close linkage without recombination between NH and the Xp loci DXS207, DXS43, and DXS365 (zmax = 3.23) was observed. Multipoint linkage analysis and the analysis of recombinations in multiple informative meioses suggest the genetic order Xcen-DMD (exon 49)-DXS451-(NH, DXS207, DXS365, DXS43)-(STS, DXF30)-Xpter. These data refine the localization of the NH locus on the distal Xp.

Distribution of lod scores in oligogenic linkage analysis.

PubMed

Williams, J T; North, K E; Martin, L J; Comuzzie, A G; Göring, H H; Blangero, J

2001-01-01

In variance component oligogenic linkage analysis it can happen that the residual additive genetic variance bounds to zero when estimating the effect of the ith quantitative trait locus. Using quantitative trait Q1 from the Genetic Analysis Workshop 12 simulated general population data, we compare the observed lod scores from oligogenic linkage analysis with the empirical lod score distribution under a null model of no linkage. We find that zero residual additive genetic variance in the null model alters the usual distribution of the likelihood-ratio statistic.

Wildlife connectivity approaches and best practices in U.S. state wildlife action plans.

PubMed

Lacher, Iara; Wilkerson, Marit L

2014-02-01

As habitat loss and fragmentation threaten biodiversity on large geographic scales, creating and maintaining connectivity of wildlife populations is an increasingly common conservation objective. To assess the progress and success of large-scale connectivity planning, conservation researchers need a set of plans that cover large geographic areas and can be analyzed as a single data set. The state wildlife action plans (SWAPs) fulfill these requirements. We examined 50 SWAPs to determine the extent to which wildlife connectivity planning, via linkages, is emphasized nationally. We defined linkage as connective land that enables wildlife movement. For our content analysis, we identified and quantified 6 keywords and 7 content criteria that ranged in specificity and were related to linkages for wide-ranging terrestrial vertebrates and examined relations between content criteria and statewide data on focal wide-ranging species, spending, revenue, and conserved land. Our results reflect nationwide disparities in linkage conservation priorities and highlight the continued need for wildlife linkage planning. Only 30% or less of the 50 SWAPs fulfilled highly specific content criteria (e.g., identifying geographic areas for linkage placement or management). We found positive correlations between our content criteria and statewide data on percent conserved land, total focal species, and spending on parks and recreation. We supplemented our content analysis with interviews with 17 conservation professionals to gain specific information about state-specific context and future directions of linkage conservation. Based on our results, relevant literature, and interview responses, we suggest the following best practices for wildlife linkage conservation plans: collect ecologically meaningful background data; be specific; establish community-wide partnerships; and incorporate sociopolitical and socioeconomic information. © 2013 Society for Conservation Biology.

Wildlife connectivity approaches and best practices in U.S. state wildlife action plans

USGS Publications Warehouse

Lacher, Iara; Wilkerson, Marit L.

2014-01-01

As habitat loss and fragmentation threaten biodiversity on large geographic scales, creating and maintaining connectivity of wildlife populations is an increasingly common conservation objective. To assess the progress and success of large-scale connectivity planning, conservation researchers need a set of plans that cover large geographic areas and can be analyzed as a single data set. The state wildlife action plans (SWAPs) fulfill these requirements. We examined 50 SWAPs to determine the extent to which wildlife connectivity planning, via linkages, is emphasized nationally. We defined linkage as connective land that enables wildlife movement. For our content analysis, we identified and quantified 6 keywords and 7 content criteria that ranged in specificity and were related to linkages for wide-ranging terrestrial vertebrates and examined relations between content criteria and statewide data on focal wide-ranging species, spending, revenue, and conserved land. Our results reflect nationwide disparities in linkage conservation priorities and highlight the continued need for wildlife linkage planning. Only 30% or less of the 50 SWAPs fulfilled highly specific content criteria (e.g., identifying geographic areas for linkage placement or management). We found positive correlations between our content criteria and statewide data on percent conserved land, total focal species, and spending on parks and recreation. We supplemented our content analysis with interviews with 17 conservation professionals to gain specific information about state-specific context and future directions of linkage conservation. Based on our results, relevant literature, and interview responses, we suggest the following best practices for wildlife linkage conservation plans: collect ecologically meaningful background data; be specific; establish community-wide partnerships; and incorporate sociopolitical and socioeconomic information.

Construction of a reference molecular linkage map of globe artichoke (Cynara cardunculus var. scolymus).

PubMed

Portis, E; Mauromicale, G; Mauro, R; Acquadro, A; Scaglione, D; Lanteri, S

2009-12-01

The genome organization of globe artichoke (Cynara cardunculus var. scolymus), unlike other species belonging to Asteraceae (=Compositae) family (i.e. sunflower, lettuce and chicory), remains largely unexplored. The species is highly heterozygous and suffers marked inbreeding depression when forced to self-fertilize. Thus a two-way pseudo-testcross represents the optimal strategy for linkage analysis. Here, we report linkage maps based on the progeny of a cross between globe artichoke (C. cardunculus var. scolymus) and cultivated cardoon (C. cardunculus var. altilis). The population was genotyped using a variety of PCR-based marker platforms, resulting in the identification of 708 testcross markers suitable for map construction. The male map consisted of 177 loci arranged in 17 major linkage groups, spanning 1,015.5 cM, while female map was built with 326 loci arranged into 20 major linkage groups, spanning 1,486.8 cM. The presence of 84 loci shared between these maps and those previously developed from a cross within globe artichoke allowed for map alignment and the definition of 17 homologous linkage groups, corresponding to the haploid number of the species. This will provide a favourable property for QTL scanning; furthermore, as 25 mapped markers (8%) correspond to coding regions, it has an additional value as functional map and might represent an important genetic tool for candidate gene studies in globe artichoke.

Nickel-Catalyzed Proton-Deuterium Exchange (HDX) Procedures for Glycosidic Linkage Analysis of Complex Carbohydrates.

PubMed

Price, Neil P J; Hartman, Trina M; Vermillion, Karl E

2015-07-21

The structural analysis of complex carbohydrates typically requires the assignment of three parameters: monosaccharide composition, the position of glycosidic linkages between monosaccharides, and the position and nature of noncarbohydrate substituents. The glycosidic linkage positions are often determined by permethylation analysis, but this can be complicated by high viscosity or poor solubility, resulting in under-methylation. This is a drawback because an under-methylated position may be misinterpreted as the erroneous site of a linkage or substituent. Here, we describe an alternative approach to linkage analysis that makes use of a nonreversible deuterium exchange of C-H protons on the carbohydrate backbone. The exchange reaction is conducted in deuterated water catalyzed by Raney nickel, and results in the selective exchange of C-H protons adjacent to free hydroxyl groups. Hence, the position of the residual C-H protons is indicative of the position of glycosidic linkages or other substituents and can be readily assigned by heteronuclear single quantum coherence-nuclear magnetic resonance (HSQC-NMR) or, following suitable derivatization, by gas chromatography-mass spectroscopy (GC/MS) analysis. Moreover, because the only changes to the parent sugar are proton/deuterium exchanges, the composition and linkage analysis can be determined in a single step.

Single-tube tetradecaplex panel of highly polymorphic microsatellite markers < 1 Mb from F8 for simplified preimplantation genetic diagnosis of hemophilia A.

PubMed

Zhao, M; Chen, M; Tan, A S C; Cheah, F S H; Mathew, J; Wong, P C; Chong, S S

2017-07-01

Essentials Preimplantation genetic diagnosis (PGD) of severe hemophilia A relies on linkage analysis. Simultaneous multi-marker screening can simplify selection of informative markers in a couple. We developed a single-tube tetradecaplex panel of polymorphic markers for hemophilia A PGD use. Informative markers can be used for linkage analysis alone or combined with mutation detection. Background It is currently not possible to perform single-cell preimplantation genetic diagnosis (PGD) to directly detect the common inversion mutations of the factor VIII (F8) gene responsible for severe hemophilia A (HEMA). As such, PGD for such inversion carriers relies on indirect analysis of linked polymorphic markers. Objectives To simplify linkage-based PGD of HEMA, we aimed to develop a panel of highly polymorphic microsatellite markers located near the F8 gene that could be simultaneously genotyped in a multiplex-PCR reaction. Methods We assessed the polymorphism of various microsatellite markers located ≤ 1 Mb from F8 in 177 female subjects. Highly polymorphic markers were selected for co-amplification with the AMELX/Y indel dimorphism in a single-tube reaction. Results Thirteen microsatellite markers located within 0.6 Mb of F8 were successfully co-amplified with AMELX/Y in a single-tube reaction. Observed heterozygosities of component markers ranged from 0.43 to 0.84, and ∼70-80% of individuals were heterozygous for ≥ 5 markers. The tetradecaplex panel successfully identified fully informative markers in a couple interested in PGD for HEMA because of an intragenic F8 point mutation, with haplotype phasing established through a carrier daughter. In-vitro fertilization (IVF)-PGD involved single-tube co-amplification of fully informative markers with AMELX/Y and the mutation-containing F8 amplicon, followed by microsatellite analysis and amplicon mutation-site minisequencing analysis. Conclusions The single-tube multiplex-PCR format of this highly polymorphic microsatellite marker panel simplifies identification and selection of informative markers for linkage-based PGD of HEMA. Informative markers can also be easily co-amplified with mutation-containing F8 amplicons for combined mutation detection and linkage analysis. © 2017 International Society on Thrombosis and Haemostasis.

Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample.

PubMed

Rademakers, Rosa; Cruts, Marc; Sleegers, Kristel; Dermaut, Bart; Theuns, Jessie; Aulchenko, Yurii; Weckx, Stefan; De Pooter, Tim; Van den Broeck, Marleen; Corsmit, Ellen; De Rijk, Peter; Del-Favero, Jurgen; van Swieten, John; van Duijn, Cornelia M; Van Broeckhoven, Christine

2005-10-01

We obtained conclusive linkage of Alzheimer disease (AD) with a candidate region of 19.7 cM at 7q36 in an extended multiplex family, family 1270, ascertained in a population-based study of early-onset AD in the northern Netherlands. Single-nucleotide polymorphism and haplotype association analyses of a Dutch patient-control sample further supported the linkage at 7q36. In addition, we identified a shared haplotype at 7q36 between family 1270 and three of six multiplex AD-affected families from the same geographical region, which is indicative of a founder effect and defines a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G-->C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1). It remains to be determined whether PAXIP1 has a functional role in the expression of AD in family 1270 or whether another mutation at this locus explains the observed linkage and sharing. Together, our linkage data from the informative family 1270 and the association data in the population-based early-onset AD patient-control sample strongly support the identification of a novel AD locus at 7q36 and re-emphasize the genetic heterogeneity of AD.

Bayesian linkage and segregation analysis: factoring the problem.

PubMed

Matthysse, S

2000-01-01

Complex segregation analysis and linkage methods are mathematical techniques for the genetic dissection of complex diseases. They are used to delineate complex modes of familial transmission and to localize putative disease susceptibility loci to specific chromosomal locations. The computational problem of Bayesian linkage and segregation analysis is one of integration in high-dimensional spaces. In this paper, three available techniques for Bayesian linkage and segregation analysis are discussed: Markov Chain Monte Carlo (MCMC), importance sampling, and exact calculation. The contribution of each to the overall integration will be explicitly discussed.

Neo-sex Chromosomes in the Monarch Butterfly, Danaus plexippus

PubMed Central

Mongue, Andrew J.; Nguyen, Petr; Voleníková, Anna; Walters, James R.

2017-01-01

We report the discovery of a neo-sex chromosome in the monarch butterfly, Danaus plexippus, and several of its close relatives. Z-linked scaffolds in the D. plexippus genome assembly were identified via sex-specific differences in Illumina sequencing coverage. Additionally, a majority of the D. plexippus genome assembly was assigned to chromosomes based on counts of one-to-one orthologs relative to the butterfly Melitaea cinxia (with replication using two other lepidopteran species), in which genome scaffolds have been mapped to linkage groups. Sequencing coverage-based assessments of Z linkage combined with homology-based chromosomal assignments provided strong evidence for a Z-autosome fusion in the Danaus lineage, involving the autosome homologous to chromosome 21 in M. cinxia. Coverage analysis also identified three notable assembly errors resulting in chimeric Z-autosome scaffolds. Cytogenetic analysis further revealed a large W chromosome that is partially euchromatic, consistent with being a neo-W chromosome. The discovery of a neo-Z and the provisional assignment of chromosome linkage for >90% of D. plexippus genes lays the foundation for novel insights concerning sex chromosome evolution in this female-heterogametic model species for functional and evolutionary genomics. PMID:28839116

Genetic Candidate Variants in Two Multigenerational Families with Childhood Apraxia of Speech

PubMed Central

Wijsman, Ellen M.; Nato, Alejandro Q.; Matsushita, Mark M.; Chapman, Kathy L.; Stanaway, Ian B.; Wolff, John; Oda, Kaori; Gabo, Virginia B.; Raskind, Wendy H.

2016-01-01

Childhood apraxia of speech (CAS) is a severe and socially debilitating form of speech sound disorder with suspected genetic involvement, but the genetic etiology is not yet well understood. Very few known or putative causal genes have been identified to date, e.g., FOXP2 and BCL11A. Building a knowledge base of the genetic etiology of CAS will make it possible to identify infants at genetic risk and motivate the development of effective very early intervention programs. We investigated the genetic etiology of CAS in two large multigenerational families with familial CAS. Complementary genomic methods included Markov chain Monte Carlo linkage analysis, copy-number analysis, identity-by-descent sharing, and exome sequencing with variant filtering. No overlaps in regions with positive evidence of linkage between the two families were found. In one family, linkage analysis detected two chromosomal regions of interest, 5p15.1-p14.1, and 17p13.1-q11.1, inherited separately from the two founders. Single-point linkage analysis of selected variants identified CDH18 as a primary gene of interest and additionally, MYO10, NIPBL, GLP2R, NCOR1, FLCN, SMCR8, NEK8, and ANKRD12, possibly with additive effects. Linkage analysis in the second family detected five regions with LOD scores approaching the highest values possible in the family. A gene of interest was C4orf21 (ZGRF1) on 4q25-q28.2. Evidence for previously described causal copy-number variations and validated or suspected genes was not found. Results are consistent with a heterogeneous CAS etiology, as is expected in many neurogenic disorders. Future studies will investigate genome variants in these and other families with CAS. PMID:27120335

Purification and partial elucidation of the structure of an antioxidant carbohydrate biopolymer from the probiotic bacterium Bacillus coagulans RK-02.

PubMed

Kodali, Vidya P; Perali, Ramu S; Sen, R

2011-08-26

An exopolysaccharide (EPS) was isolated from Bacillus coagulans RK-02 and purified by size exclusion chromatography. The purified, homogeneous EPS had an average molecular weight of ∼3 × 10⁴ Da by comparison with FITC-labeled dextran standards. In vivo evaluations showed that, like other reported polysaccharides, this EPS displayed significant antioxidant activity. FTIR spectroscopy analysis showed the presence of hydroxy, carboxy, and α-glycosidic linkages and a mannose residue. GC analysis indicated that the EPS was a heteropolymer composed of glucose, mannose, galactose, glucosamine, and fucose as monomeric constituent units. Partial elucidation of the structure of the carbohydrate biopolymer based on GC-MS and NMR analysis showed the presence of two unique sets of tetrasaccharide repeating units that have 1→3 and 1→6 glycosidic linkages. This is also the first report of a Gram-positive bacterial polysaccharide with both fucose as a sugar monomer and 1→3 and 1→6 glycosidic linkages in the molecular backbone.

Genotyping by Sequencing in Almond: SNP Discovery, Linkage Mapping, and Marker Design

PubMed Central

Goonetilleke, Shashi N.; March, Timothy J.; Wirthensohn, Michelle G.; Arús, Pere; Walker, Amanda R.; Mather, Diane E.

2017-01-01

In crop plant genetics, linkage maps provide the basis for the mapping of loci that affect important traits and for the selection of markers to be applied in crop improvement. In outcrossing species such as almond (Prunus dulcis Mill. D. A. Webb), application of a double pseudotestcross mapping approach to the F1 progeny of a biparental cross leads to the construction of a linkage map for each parent. Here, we report on the application of genotyping by sequencing to discover and map single nucleotide polymorphisms in the almond cultivars “Nonpareil” and “Lauranne.” Allele-specific marker assays were developed for 309 tag pairs. Application of these assays to 231 Nonpareil × Lauranne F1 progeny provided robust linkage maps for each parent. Analysis of phenotypic data for shell hardness demonstrated the utility of these maps for quantitative trait locus mapping. Comparison of these maps to the peach genome assembly confirmed high synteny and collinearity between the peach and almond genomes. The marker assays were applied to progeny from several other Nonpareil crosses, providing the basis for a composite linkage map of Nonpareil. Applications of the assays to a panel of almond clones and a panel of rootstocks used for almond production demonstrated the broad applicability of the markers and provide subsets of markers that could be used to discriminate among accessions. The sequence-based linkage maps and single nucleotide polymorphism assays presented here could be useful resources for the genetic analysis and genetic improvement of almond. PMID:29141988

A supported employment linkage intervention for people with schizophrenia who want a chance to work.

PubMed

Solar, Ann

2014-06-01

Investigate feasibility and development of a linkage intervention to the evidence-based Individual Placement and Support (IPS) approach to supported employment (SE) for patients with schizophrenia on a mental health unit who want to work in competitive employment. Literature review about the evidence-based IPS approach to SE in schizophrenia and why it might not be implemented in mental health services. Analysis of 10 adult mental health unit multidisciplinary staff interviews for categories in the literature review of IPS implementation barriers and whether these barriers could be overcome. There was lack of full staff knowledge of the IPS approach to SE. However, all staff knew respect for patient choice was paramount, community employment programs existed for the disabled, an outreach linkage process to such a program and ongoing support for people with schizophrenia would be required. There was staff ambivalence about SE for patients with schizophrenia. Despite staff ambivalence about SE for people with schizophrenia there was still enough staff knowledge and openness to shape an IPS linkage intervention from a staff perspective. © The Royal Australian and New Zealand College of Psychiatrists 2014.

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

PubMed Central

Abdallah, Jihad M; Goffinet, Bruno; Cierco-Ayrolles, Christine; Pérez-Enciso, Miguel

2003-01-01

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. PMID:12939203

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

PubMed

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

2016-01-01

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

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

PubMed Central

Fang, Lecheng; Li, Xiaoping; Yin, Tongming

2016-01-01

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tahvanainen, E.; Karila, E.; Kolehmainen, J.

We recently assigned a gene for autosomal recessive cornea plana congenita (CNA2; MIM No. 217300) by linkage analysis to the approximately 3-cM interval between markers D12S82 and D12S327. Here, we extended these studies by exploiting the haplotype and linkage disequilibrium information that can be derived from the genetically isolated Finnish population and its subpopulations. By testing 32 independent families with 10 polymorphic markers in the CNA2 interval, strong allelic association between CNA2 and a set of markers with a peak at marker D12S351 was detected. Based on linkage disequilibrium analysis, the critical region for CNA2 could be narrowed to onlymore » 0.04-0.3 cM from marker D12S351, thus defining a critical interval 0.08-0.60 cM in length. These results provide a basis for highly focused positional cloning of CNA2. 18 refs., 5 figs., 1 tab.« less

Localization of an Ataxia-Telangiectasia Gene to an −500-kb Interval on Chromosome 11q23.1: Linkage Analysis of 176 Families by an International Consortium

PubMed Central

Lange, Ethan; Borresen, Anna-Lise; Chen, Xiaoguang; Chessa, Luciana; Chiplunkar, Sujata; Concannon, Patrick; Dandekar, Sugandha; Gerken, Steven; Lange, Kenneth; Liang, Teresa; McConville, Carmel; Polakow, Jeff; Porras, Oscar; Rotman, Galit; Sanal, Ozden; Sheikhavandi, Sepideh; Shiloh, Yosef; Sobel, Eric; Taylor, Malcolm; Telatar, Milhan; Teraoka, Sharon; Tolun, Aslihan; Udar, Nitin; Uhrhammer, Nancy; Vanagaite, Lina; Wang, Zhijun; Wapelhorst, Beth; Wright, Jocyndra; Yang, Huan-Ming; Yang, Lan; Ziv, Yael; Gatti, Richard A.

1995-01-01

We describe a 20-point linkage analysis map of chromosome 11q22-23 that is based on genotyping 249 families (59 CEPH and 190 A-T). Monte Carlo linkage analyses of 176 ataxia-telangiectasia (A-T) families localizes the major A-T locus to the region between S1819(A4) and S1818(A2). When seven nonlinking families were excluded from subsequent analyses, a 2-lod support interval of ∼500 kb was identified between S1819(A4) and S1294. No recombinants were observed between A-T and markers S384, B7, S535, or S1294. Only 17 of the international consortium families have been assigned to complementation groups. The available evidence favors either a cluster of A-T genes on chromosome 11 or intragenic defects in a single gene. PMID:7611279

Privacy preserving interactive record linkage (PPIRL).

PubMed

Kum, Hye-Chung; Krishnamurthy, Ashok; Machanavajjhala, Ashwin; Reiter, Michael K; Ahalt, Stanley

2014-01-01

Record linkage to integrate uncoordinated databases is critical in biomedical research using Big Data. Balancing privacy protection against the need for high quality record linkage requires a human-machine hybrid system to safely manage uncertainty in the ever changing streams of chaotic Big Data. In the computer science literature, private record linkage is the most published area. It investigates how to apply a known linkage function safely when linking two tables. However, in practice, the linkage function is rarely known. Thus, there are many data linkage centers whose main role is to be the trusted third party to determine the linkage function manually and link data for research via a master population list for a designated region. Recently, a more flexible computerized third-party linkage platform, Secure Decoupled Linkage (SDLink), has been proposed based on: (1) decoupling data via encryption, (2) obfuscation via chaffing (adding fake data) and universe manipulation; and (3) minimum information disclosure via recoding. We synthesize this literature to formalize a new framework for privacy preserving interactive record linkage (PPIRL) with tractable privacy and utility properties and then analyze the literature using this framework. Human-based third-party linkage centers for privacy preserving record linkage are the accepted norm internationally. We find that a computer-based third-party platform that can precisely control the information disclosed at the micro level and allow frequent human interaction during the linkage process, is an effective human-machine hybrid system that significantly improves on the linkage center model both in terms of privacy and utility.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kendler, K.S.; Straub, R.E.; MacLean, C.J.

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/ormore » 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.« less

Linkage to HIV care after home-based HIV counselling and testing in sub-Saharan Africa: a systematic review.

PubMed

Ruzagira, Eugene; Baisley, Kathy; Kamali, Anatoli; Biraro, Samuel; Grosskurth, Heiner

2017-07-01

Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA), but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA. Five databases were searched for studies published between 1st January 2000 and 19th August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines. A total of 14 studies from six countries met the eligibility criteria; nine used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8-9.8%] to 99.1% (95% CI, 96.9-99.9%). Linkage was generally lower (<33%) if HBHCT was followed by referral only, and higher (>80%) if additional strategies were used. Only one study assessed linkage by means of a randomised trial. Five studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36-57.9%) to 94.9% (95% CI, 91.3-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting and the key variable definitions. Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through HBHCT. Linkage was often low after routine referral but higher if additional interventions were used to facilitate it. The effectiveness of linkage strategies should be confirmed through randomised controlled trials. © 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Nickel-catalyzed proton-deuterium exchange (HDX) procedures for glycosidic linkage analysis of complex carbohydrates

USDA-ARS?s Scientific Manuscript database

The structural analysis of complex carbohydrates typically requires the assignment of three parameters: monosaccharide composition, the position of glycosidic linkages between monosaccharides, and the position and nature of non-carbohydrate substituents. The glycosidic linkage positions are often de...

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

PubMed

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.

Nickel-catalyzed proton-deuterium exchange (HDX) for linkage analysis of complex carbohydrates

USDA-ARS?s Scientific Manuscript database

The structural assignment of complex carbohydrates typically requires the analysis of at least three parameters: 1. composition; 2. linkage; and 3. substituents. These are often assigned on a small scale by gas chromatography/mass spectrometry (GC/MS). Linkage positions are determined by permethylat...

Privacy preserving interactive record linkage (PPIRL)

PubMed Central

Kum, Hye-Chung; Krishnamurthy, Ashok; Machanavajjhala, Ashwin; Reiter, Michael K; Ahalt, Stanley

2014-01-01

Objective Record linkage to integrate uncoordinated databases is critical in biomedical research using Big Data. Balancing privacy protection against the need for high quality record linkage requires a human–machine hybrid system to safely manage uncertainty in the ever changing streams of chaotic Big Data. Methods In the computer science literature, private record linkage is the most published area. It investigates how to apply a known linkage function safely when linking two tables. However, in practice, the linkage function is rarely known. Thus, there are many data linkage centers whose main role is to be the trusted third party to determine the linkage function manually and link data for research via a master population list for a designated region. Recently, a more flexible computerized third-party linkage platform, Secure Decoupled Linkage (SDLink), has been proposed based on: (1) decoupling data via encryption, (2) obfuscation via chaffing (adding fake data) and universe manipulation; and (3) minimum information disclosure via recoding. Results We synthesize this literature to formalize a new framework for privacy preserving interactive record linkage (PPIRL) with tractable privacy and utility properties and then analyze the literature using this framework. Conclusions Human-based third-party linkage centers for privacy preserving record linkage are the accepted norm internationally. We find that a computer-based third-party platform that can precisely control the information disclosed at the micro level and allow frequent human interaction during the linkage process, is an effective human–machine hybrid system that significantly improves on the linkage center model both in terms of privacy and utility. PMID:24201028

Localization of genes involved in the metabolic syndrome using multivariate linkage analysis.

PubMed

Olswold, Curtis; de Andrade, Mariza

2003-12-31

There are no well accepted criteria for the diagnosis of the metabolic syndrome. However, the metabolic syndrome is identified clinically by the presence of three or more of these five variables: larger waist circumference, higher triglyceride levels, lower HDL-cholesterol concentrations, hypertension, and impaired fasting glucose. We use sets of two or three variables, which are available in the Framingham Heart Study data set, to localize genes responsible for this syndrome using multivariate quantitative linkage analysis. This analysis demonstrates the applicability of using multivariate linkage analysis and how its use increases the power to detect linkage when genes are involved in the same disease mechanism.

Genetic Structure, Linkage Disequilibrium and Association Mapping of Verticillium Wilt Resistance in Elite Cotton (Gossypium hirsutum L.) Germplasm Population

PubMed Central

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 (P<0.001) in this association panel. The LD level for linked markers is significantly higher than that for unlinked markers, suggesting that physical linkage strongly influences LD in this panel, and LD level was elevated when the panel was classified into groups and subgroups. The LD decay analysis for several chromosomes showed that different chromosomes showed a notable change in LD decay distances for the same gene pool. Based on the disease nursery and greenhouse environment, 42 marker loci associated with Verticillium wilt resistance were identified through association mapping, 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. PMID:24466016

Relative Linkages of Stream Dissolved Oxygen with the Climatic, Hydrological, and Biogeochemical Drivers across the East Coast of U.S.A.

NASA Astrophysics Data System (ADS)

Abdul-Aziz, O. I.; Ahmed, S.

2017-12-01

Dissolved oxygen (DO) is a key indicator of stream water quality and ecosystem health. However, the temporal dynamics of stream DO is controlled by a multitude of interacting environmental drivers. The relative linkages of stream DO with the relevant environmental drivers were determined in this study across the U.S. East Coast by employing a systematic data analytics approach. The study analyzed temporal data for 51 water quality monitoring stations from USGS NWIS and EPA STORET databases. Principal component analysis and factor analysis, along with Pearson's correlation analysis, were applied to identify the interrelationships and unravel latent patterns among DO and the environmental drivers. Power law based partial least squares regression models with a bootstarp Monte-Carlo procedure (1000 iterations) were developed to reliably estimate the environmental linkages of DO by resolving multicollinearity. Based on the similarity of dominant drivers, the streams were categorized into three distinct environmental regimes. Stream DO in the northern part of temperate zone (e.g., northeast coast) had the strongest linkage with water temperature; suggesting an environmental regime with dominant climatic control. However, stream DO in the tropical zones (e.g., southeast Florida) was mostly driven by pH; indicating an environmental regime likely controlled by redox chemistry. Further, a transitional regime was found between the temperate and tropical zones, where stream DO was controlled by both water temperature and pH. The results suggested a strong effect of the climatic gradient (temperate to tropical) on stream DO along the East Coast. The identified environmental regimes and the regime-specific relative linkages provided new information on the dominant controls of coastal stream water quality dynamics. The findings would guide the planning and management of coastal stream water quality and ecosystem health across the U.S. East Coast and around the world.

A systematic review and meta-analysis of community and facility-based approaches to address gaps in HIV testing and linkage in sub-Saharan Africa

PubMed Central

Sharma, Monisha; Ying, Roger; Tarr, Gillian; Barnabas, Ruanne

2016-01-01

HIV testing and counselling is the first crucial step for linkage to HIV treatment and prevention. However, despite high HIV burden in sub-Saharan Africa, testing coverage is low, particularly among young adults and men. Community-based HIV testing and counselling (testing outside of health facilities) has the potential to reduce coverage gaps, but the relative impact of different modalities is not well assessed. We conducted a systematic review of HIV testing and counselling modalities, characterizing facility and community (home, mobile, index, key populations, campaign, workplace and self-testing) approaches by population reached, HIV-positivity, CD4 count at diagnosis and linkage. Of 2,520 abstracts screened, 126 met eligibility criteria. Community HIV testing had high coverage and uptake and identified HIV-positive individuals at higher CD4 counts than facility testing. Mobile HIV testing reached the highest proportion of men of all modalities examined (50%, 95% CI = 47–54%) and home with self-testing reached the highest proportion of young adults (66%, 95% CI = 65–67%). Few studies evaluated HIV testing and counselling for key populations (commercial sex workers and men who have sex with men), but these interventions yielded high HIV positivity (38%, 95% CI = 19–62%) combined with the highest proportion of first-time testers (78%, 95% CI = 63–88%), indicating service gaps. Facilitated linkage (for example, counsellor follow-up to support linkage) achieved high linkage to care (95%, 95% CI = 87–98%) and ART initiation (75%, 95% CI = 68–82%). Expanding mobile HIV testing, self-testing and outreach to key populations with facilitated linkage can increase the proportion of men, young adults and high-risk individuals linked to HIV treatment and prevention. PMID:26633769

A guide to evaluating linkage quality for the analysis of linked data.

PubMed

Harron, Katie L; Doidge, James C; Knight, Hannah E; Gilbert, Ruth E; Goldstein, Harvey; Cromwell, David A; van der Meulen, Jan H

2017-10-01

Linked datasets are an important resource for epidemiological and clinical studies, but linkage error can lead to biased results. For data security reasons, linkage of personal identifiers is often performed by a third party, making it difficult for researchers to assess the quality of the linked dataset in the context of specific research questions. This is compounded by a lack of guidance on how to determine the potential impact of linkage error. We describe how linkage quality can be evaluated and provide widely applicable guidance for both data providers and researchers. Using an illustrative example of a linked dataset of maternal and baby hospital records, we demonstrate three approaches for evaluating linkage quality: applying the linkage algorithm to a subset of gold standard data to quantify linkage error; comparing characteristics of linked and unlinked data to identify potential sources of bias; and evaluating the sensitivity of results to changes in the linkage procedure. These approaches can inform our understanding of the potential impact of linkage error and provide an opportunity to select the most appropriate linkage procedure for a specific analysis. Evaluating linkage quality in this way will improve the quality and transparency of epidemiological and clinical research using linked data. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

Genetic mapping of 15 human X chromosomal forensic short tandem repeat (STR) loci by means of multi-core parallelization.

PubMed

Diegoli, Toni Marie; Rohde, Heinrich; Borowski, Stefan; Krawczak, Michael; Coble, Michael D; Nothnagel, Michael

2016-11-01

Typing of X chromosomal short tandem repeat (X STR) markers has become a standard element of human forensic genetic analysis. Joint consideration of many X STR markers at a time increases their discriminatory power but, owing to physical linkage, requires inter-marker recombination rates to be accurately known. We estimated the recombination rates between 15 well established X STR markers using genotype data from 158 families (1041 individuals) and following a previously proposed likelihood-based approach that allows for single-step mutations. To meet the computational requirements of this family-based type of analysis, we modified a previous implementation so as to allow multi-core parallelization on a high-performance computing system. While we obtained recombination rate estimates larger than zero for all but one pair of adjacent markers within the four previously proposed linkage groups, none of the three X STR pairs defining the junctions of these groups yielded a recombination rate estimate of 0.50. Corroborating previous studies, our results therefore argue against a simple model of independent X chromosomal linkage groups. Moreover, the refined recombination fraction estimates obtained in our study will facilitate the appropriate joint consideration of all 15 investigated markers in forensic analysis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Caucasian Families Exhibit Significant Linkage of Myopia to Chromosome 11p.

PubMed

Musolf, Anthony M; Simpson, Claire L; Moiz, Bilal A; Long, Kyle A; Portas, Laura; Murgia, Federico; Ciner, Elise B; Stambolian, Dwight; Bailey-Wilson, Joan E

2017-07-01

Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.

Linkage of Recognition and Replication Functions by Assembling Combinatorial Antibody Fab Libraries Along Phage Surfaces

NASA Astrophysics Data System (ADS)

Kang, Angray S.; Barbas, Carlos F.; Janda, Kim D.; Benkovic, Stephen J.; Lerner, Richard A.

1991-05-01

We describe a method based on a phagemid vector with helper phage rescue for the construction and rapid analysis of combinatorial antibody Fab libraries. This approach should allow the generation and selection of many monoclonal antibodies. Antibody genes are expressed in concert with phage morphogenesis, thereby allowing incorporation of functional Fab molecules along the surface of filamentous phage. The power of the method depends upon the linkage of recognition and replication functions and is not limited to antibody molecules.

How home HIV testing and counselling with follow-up support achieves high testing coverage and linkage to treatment and prevention: a qualitative analysis from Uganda.

PubMed

Ware, Norma C; Wyatt, Monique A; Asiimwe, Stephen; Turyamureeba, Bosco; Tumwesigye, Elioda; van Rooyen, Heidi; Barnabas, Ruanne V; Celum, Connie L

2016-01-01

The successes of HIV treatment scale-up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended. Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels, followed by linkage to treatment or prevention. As effective linkage strategies are identified, it becomes important to understand how these strategies work. We use qualitative data from The Linkages Study, a recent community intervention trial of community-based testing with linkage interventions in sub-Saharan Africa, to show how lay counsellor home HIV testing and counselling (home HTC) with follow-up support leads to linkage to clinic-based HIV treatment and medical male circumcision services. We conducted 99 semi-structured individual interviews with study participants and three focus groups with 16 lay counsellors in Kabwohe, Sheema District, Uganda. The participant sample included both HIV+ men and women (N=47) and HIV-uncircumcised men (N=52). Interview and focus group audio-recordings were translated and transcribed. Each transcript was summarized. The summaries were analyzed inductively to identify emergent themes. Thematic concepts were grouped to develop general constructs and framing propositional statements. Trial participants expressed interest in linking to clinic-based services at testing, but faced obstacles that eroded their initial enthusiasm. Follow-up support by lay counsellors intervened to restore interest and inspire action. Together, home HTC and follow-up support improved morale, created a desire to reciprocate, and provided reassurance that services were trustworthy. In different ways, these functions built links to the health service system. They worked to strengthen individuals' general sense of capability, while making the idea of accessing services more manageable and familiar, thus reducing linkage barriers. Home HTC with follow-up support leads to linkage by building "social bridges," interpersonal connections established and developed through repeated face-to-face contact between counsellors and prospective users of HIV treatment and male circumcision services. Social bridges link communities to the service system, inspiring individuals to overcome obstacles and access care.

Linkage and Branch Analysis of High-Mannose Oligosaccharides Using Closed-Ring Labeling of 8-Aminopyrene-1,3,6-Trisulfonate and P-Aminobenzoic Ethyl Ester and Negative Ion Trap Mass Spectrometry

NASA Astrophysics Data System (ADS)

Chen, Shu-Ting; Her, Guor-Rong

2012-08-01

A strategy based on negative ion electrospray ionization tandem mass spectrometry and closed-ring labeling with both 8-aminopyrene-1,3,6-trisulfonate (APTS) and p-aminobenzoic acid ethyl ester (ABEE) was developed for linkage and branch determination of high-mannose oligosaccharides. X-type cross-ring fragment ions obtained from APTS-labeled oligosaccharides by charge remote fragmentation provided information on linkages near the non-reducing terminus. In contrast, A-type cross-ring fragment ions observed from ABEE-labeled oligosaccharides yielded information on linkages near the reducing terminus. This complementary information provided by APTS- and ABEE-labeled oligosaccharides was utilized to delineate the structures of the high-mannose oligosaccharides. As a demonstration of this approach, the linkages and branches of high-mannose oligosaccharides Man5GlcNAc2, Man6GlcNAc2, Man8GlcNAc2, and Man9GlcNAc2 cleaved from the ribonuclease B were assigned from MS2 spectra of ABEE- and APTS-labeled derivatives.

Evidence of Allopolyploidy in Urochloa humidicola Based on Cytological Analysis and Genetic Linkage Mapping

PubMed Central

Vigna, Bianca B. Z.; Santos, Jean C. S.; Jungmann, Leticia; do Valle, Cacilda B.; Mollinari, Marcelo; Pastina, Maria M.; Garcia, Antonio A. F.

2016-01-01

The African species Urochloa humidicola (Rendle) Morrone & Zuloaga (syn. Brachiaria humidicola (Rendle) Schweick.) is an important perennial forage grass found throughout the tropics. This species is polyploid, ranging from tetra to nonaploid, and apomictic, which makes genetic studies challenging; therefore, the number of currently available genetic resources is limited. The genomic architecture and evolution of U. humidicola and the molecular markers linked to apomixis were investigated in a full-sib F1 population obtained by crossing the sexual accession H031 and the apomictic cultivar U. humidicola cv. BRS Tupi, both of which are hexaploid. A simple sequence repeat (SSR)-based linkage map was constructed for the species from 102 polymorphic and specific SSR markers based on simplex and double-simplex markers. The map consisted of 49 linkage groups (LGs) and had a total length of 1702.82 cM, with 89 microsatellite loci and an average map density of 10.6 cM. Eight homology groups (HGs) were formed, comprising 22 LGs, and the other LGs remained ungrouped. The locus that controls apospory (apo-locus) was mapped in LG02 and was located 19.4 cM from the locus Bh027.c.D2. In the cytological analyses of some hybrids, bi- to hexavalents at diakinesis were observed, as well as two nucleoli in some meiocytes, smaller chromosomes with preferential allocation within the first metaphase plate and asynchronous chromosome migration to the poles during anaphase. The linkage map and the meiocyte analyses confirm previous reports of hybridization and suggest an allopolyploid origin of the hexaploid U. humidicola. This is the first linkage map of an Urochloa species, and it will be useful for future quantitative trait locus (QTL) analysis after saturation of the map and for genome assembly and evolutionary studies in Urochloa spp. Moreover, the results of the apomixis mapping are consistent with previous reports and confirm the need for additional studies to search for a co-segregating marker. PMID:27104622

Genome-Wide Linkage Analysis to Identify Genetic Modifiers of ALK Mutation Penetrance in Familial Neuroblastoma

PubMed Central

Devoto, Marcella; Specchia, Claudia; Laudenslager, Marci; Longo, Luca; Hakonarson, Hakon; Maris, John; Mossé, Yael

2011-01-01

Background Neuroblastoma (NB) is an important childhood cancer with a strong genetic component related to disease susceptibility. Approximately 1% of NB cases have a positive family history. Following a genome-wide linkage analysis and sequencing of candidate genes in the critical region, we identified ALK as the major familial NB gene. Dominant mutations in ALK are found in more than 50% of familial NB cases. However, in the families used for the linkage study, only about 50% of carriers of ALK mutations are affected by NB. Methods To test whether genetic variation may explain the reduced penetrance of the disease phenotype, we analyzed genome-wide genotype data in ALK mutation-positive families using a model-based linkage approach with different liability classes for carriers and non-carriers of ALK mutations. Results The region with the highest LOD score was located at chromosome 2p23–p24 and included the ALK locus under models of dominant and recessive inheritance. Conclusions This finding suggests that variants in the non-mutated ALK gene or another gene linked to it may affect penetrance of the ALK mutations and risk of developing NB in familial cases. PMID:21734404

Genotyping by Sequencing in Almond: SNP Discovery, Linkage Mapping, and Marker Design.

PubMed

Goonetilleke, Shashi N; March, Timothy J; Wirthensohn, Michelle G; Arús, Pere; Walker, Amanda R; Mather, Diane E

2018-01-04

In crop plant genetics, linkage maps provide the basis for the mapping of loci that affect important traits and for the selection of markers to be applied in crop improvement. In outcrossing species such as almond ( Prunus dulcis Mill. D. A. Webb), application of a double pseudotestcross mapping approach to the F 1 progeny of a biparental cross leads to the construction of a linkage map for each parent. Here, we report on the application of genotyping by sequencing to discover and map single nucleotide polymorphisms in the almond cultivars "Nonpareil" and "Lauranne." Allele-specific marker assays were developed for 309 tag pairs. Application of these assays to 231 Nonpareil × Lauranne F 1 progeny provided robust linkage maps for each parent. Analysis of phenotypic data for shell hardness demonstrated the utility of these maps for quantitative trait locus mapping. Comparison of these maps to the peach genome assembly confirmed high synteny and collinearity between the peach and almond genomes. The marker assays were applied to progeny from several other Nonpareil crosses, providing the basis for a composite linkage map of Nonpareil. Applications of the assays to a panel of almond clones and a panel of rootstocks used for almond production demonstrated the broad applicability of the markers and provide subsets of markers that could be used to discriminate among accessions. The sequence-based linkage maps and single nucleotide polymorphism assays presented here could be useful resources for the genetic analysis and genetic improvement of almond. Copyright © 2018 Goonetilleke et al.

Mapping Quantitative Field Resistance Against Apple Scab in a 'Fiesta' x 'Discovery' Progeny.

PubMed

Liebhard, R; Koller, B; Patocchi, A; Kellerhals, M; Pfammatter, W; Jermini, M; Gessler, C

2003-04-01

ABSTRACT Breeding of resistant apple cultivars (Malus x domestica) as a disease management strategy relies on the knowledge and understanding of the underlying genetics. The availability of molecular markers and genetic linkage maps enables the detection and the analysis of major resistance genes as well as of quantitative trait loci (QTL) contributing to the resistance of a genotype. Such a genetic linkage map was constructed, based on a segregating population of the cross between apple cvs. Fiesta (syn. Red Pippin) and Discovery. The progeny was observed for 3 years at three different sites in Switzerland and field resistance against apple scab (Venturia inaequalis) was assessed. Only a weak correlation was detected between leaf scab and fruit scab. A QTL analysis was performed, based on the genetic linkage map consisting of 804 molecular markers and covering all 17 chromosomes of apple. With the maximum likelihood-based interval mapping method, eight genomic regions were identified, six conferring resistance against leaf scab and two conferring fruit scab resistance. Although cv. Discovery showed a much stronger resistance against scab in the field, most QTL identified were attributed to the more susceptible parent 'Fiesta'. This indicated a high degree of homozygosity at the scab resistance loci in 'Discovery', preventing their detection in the progeny due to the lack of segregation.

A Targeted Capture Linkage Map Anchors the Genome of the Schistosomiasis Vector Snail, Biomphalaria glabrata.

PubMed

Tennessen, Jacob A; Bollmann, Stephanie R; Blouin, Michael S

2017-07-05

The aquatic planorbid snail Biomphalaria glabrata is one of the most intensively-studied mollusks due to its role in the transmission of schistosomiasis. Its 916 Mb genome has recently been sequenced and annotated, but it remains poorly assembled. Here, we used targeted capture markers to map over 10,000 B. glabrata scaffolds in a linkage cross of 94 F1 offspring, generating 24 linkage groups (LGs). We added additional scaffolds to these LGs based on linkage disequilibrium (LD) analysis of targeted capture and whole-genome sequences of 96 unrelated snails. Our final linkage map consists of 18,613 scaffolds comprising 515 Mb, representing 56% of the genome and 75% of genic and nonrepetitive regions. There are 18 large (> 10 Mb) LGs, likely representing the expected 18 haploid chromosomes, and > 50% of the genome has been assigned to LGs of at least 17 Mb. Comparisons with other gastropod genomes reveal patterns of synteny and chromosomal rearrangements. Linkage relationships of key immune-relevant genes may help clarify snail-schistosome interactions. By focusing on linkage among genic and nonrepetitive regions, we have generated a useful resource for associating snail phenotypes with causal genes, even in the absence of a complete genome assembly. A similar approach could potentially improve numerous poorly-assembled genomes in other taxa. This map will facilitate future work on this host of a serious human parasite. Copyright © 2017 Tennessen et al.

SNP Discovery and Linkage Map Construction in Cultivated Tomato

PubMed Central

Shirasawa, Kenta; Isobe, Sachiko; Hirakawa, Hideki; Asamizu, Erika; Fukuoka, Hiroyuki; Just, Daniel; Rothan, Christophe; Sasamoto, Shigemi; Fujishiro, Tsunakazu; Kishida, Yoshie; Kohara, Mitsuyo; Tsuruoka, Hisano; Wada, Tsuyuko; Nakamura, Yasukazu; Sato, Shusei; Tabata, Satoshi

2010-01-01

Few intraspecific genetic linkage maps have been reported for cultivated tomato, mainly because genetic diversity within Solanum lycopersicum is much less than that between tomato species. Single nucleotide polymorphisms (SNPs), the most abundant source of genomic variation, are the most promising source of polymorphisms for the construction of linkage maps for closely related intraspecific lines. In this study, we developed SNP markers based on expressed sequence tags for the construction of intraspecific linkage maps in tomato. Out of the 5607 SNP positions detected through in silico analysis, 1536 were selected for high-throughput genotyping of two mapping populations derived from crosses between ‘Micro-Tom’ and either ‘Ailsa Craig’ or ‘M82’. A total of 1137 markers, including 793 out of the 1338 successfully genotyped SNPs, along with 344 simple sequence repeat and intronic polymorphism markers, were mapped onto two linkage maps, which covered 1467.8 and 1422.7 cM, respectively. The SNP markers developed were then screened against cultivated tomato lines in order to estimate the transferability of these SNPs to other breeding materials. The molecular markers and linkage maps represent a milestone in the genomics and genetics, and are the first step toward molecular breeding of cultivated tomato. Information on the DNA markers, linkage maps, and SNP genotypes for these tomato lines is available at http://www.kazusa.or.jp/tomato/. PMID:21044984

Effects of naloxone distribution alone or in combination with addiction treatment with or without pre-exposure prophylaxis for HIV prevention in people who inject drugs: a cost-effectiveness modelling study.

PubMed

Uyei, Jennifer; Fiellin, David A; Buchelli, Marianne; Rodriguez-Santana, Ramon; Braithwaite, R Scott

2017-03-01

In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP. We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained. In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a willingness-to-pay threshold of $100 000. In probabilistic sensitivity analysis, the combination of naloxone distribution, PrEP, and linkage to addiction treatment was the optimal strategy in 37% of iterations and the combination of naloxone distribution and linkage to addiction treatment was the optimal strategy in 34% of iterations. Naloxone distribution through syringe service programmes is cost-effective compared with syringe distribution alone, but when combined with linkage to addiction treatment is cost saving compared with no additional services. A strategy that combines naloxone distribution, PrEP, and linkage to addiction treatment results in greater health benefits in people who inject drugs and is also cost-effective. State of Connecticut Department of Public Health and the National Institute of Mental Health. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Accommodating Chromosome Inversions in Linkage Analysis

PubMed Central

Chen, Gary K.; Slaten, Erin; Ophoff, Roel A.; Lange, Kenneth

2006-01-01

This work develops a population-genetics model for polymorphic chromosome inversions. The model precisely describes how an inversion changes the nature of and approach to linkage equilibrium. The work also describes algorithms and software for allele-frequency estimation and linkage analysis in the presence of an inversion. The linkage algorithms implemented in the software package Mendel estimate recombination parameters and calculate the posterior probability that each pedigree member carries the inversion. Application of Mendel to eight Centre d'Étude du Polymorphisme Humain pedigrees in a region containing a common inversion on 8p23 illustrates its potential for providing more-precise estimates of the location of an unmapped marker or trait gene. Our expanded cytogenetic analysis of these families further identifies inversion carriers and increases the evidence of linkage. PMID:16826515

Conclusion of LOD-score analysis for family data generated under two-locus models.

PubMed

Dizier, M H; Babron, M C; Clerget-Darpoux, F

1996-06-01

The power to detect linkage by the LOD-score method is investigated here for diseases that depend on the effects of two genes. The classical strategy is, first, to detect a major-gene (MG) effect by segregation analysis and, second, to seek for linkage with genetic markers by the LOD-score method using the MG parameters. We already showed that segregation analysis can lead to evidence for a MG effect for many two-locus models, with the estimates of the MG parameters being very different from those of the two genes involved in the disease. We show here that use of these MG parameter estimates in the LOD-score analysis may lead to a failure to detect linkage for some two-locus models. For these models, use of the sib-pair method gives a non-negligible increase of power to detect linkage. The linkage-homogeneity test among subsamples differing for the familial disease distribution provides evidence of parameter misspecification, when the MG parameters are used. Moreover, for most of the models, use of the MG parameters in LOD-score analysis leads to a large bias in estimation of the recombination fraction and sometimes also to a rejection of linkage for the true recombination fraction. A final important point is that a strong evidence of an MG effect, obtained by segregation analysis, does not necessarily imply that linkage will be detected for at least one of the two genes, even with the true parameters and with a close informative marker.

Fine mapping on chromosome 13q32-34 and brain expression analysis implicates MYO16 in schizophrenia.

PubMed

Rodriguez-Murillo, Laura; Xu, Bin; Roos, J Louw; Abecasis, Gonçalo R; Gogos, Joseph A; Karayiorgou, Maria

2014-03-01

We previously reported linkage of schizophrenia and schizoaffective disorder to 13q32-34 in the European descent Afrikaner population from South Africa. The nature of genetic variation underlying linkage peaks in psychiatric disorders remains largely unknown and both rare and common variants may be contributing. Here, we examine the contribution of common variants located under the 13q32-34 linkage region. We used densely spaced SNPs to fine map the linkage peak region using both a discovery sample of 415 families and a meta-analysis incorporating two additional replication family samples. In a second phase of the study, we use one family-based data set with 237 families and independent case-control data sets for fine mapping of the common variant association signal using HapMap SNPs. We report a significant association with a genetic variant (rs9583277) within the gene encoding for the myosin heavy-chain Myr 8 (MYO16), which has been implicated in neuronal phosphoinositide 3-kinase signaling. Follow-up analysis of HapMap variation within MYO16 in a second set of Afrikaner families and additional case-control data sets of European descent highlighted a region across introns 2-6 as the most likely region to harbor common MYO16 risk variants. Expression analysis revealed a significant increase in the level of MYO16 expression in the brains of schizophrenia patients. Our results suggest that common variation within MYO16 may contribute to the genetic liability to schizophrenia.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1993-11-01

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

High-resolution melt analysis to identify and map sequence-tagged site anchor points onto linkage maps: a white lupin (Lupinus albus) map as an exemplar.

PubMed

Croxford, Adam E; Rogers, Tom; Caligari, Peter D S; Wilkinson, Michael J

2008-01-01

* The provision of sequence-tagged site (STS) anchor points allows meaningful comparisons between mapping studies but can be a time-consuming process for nonmodel species or orphan crops. * Here, the first use of high-resolution melt analysis (HRM) to generate STS markers for use in linkage mapping is described. This strategy is rapid and low-cost, and circumvents the need for labelled primers or amplicon fractionation. * Using white lupin (Lupinus albus, x = 25) as a case study, HRM analysis was applied to identify 91 polymorphic markers from expressed sequence tag (EST)-derived and genomic libraries. Of these, 77 generated STS anchor points in the first fully resolved linkage map of the species. The map also included 230 amplified fragment length polymorphisms (AFLP) loci, spanned 1916 cM (84.2% coverage) and divided into the expected 25 linkage groups. * Quantitative trait loci (QTL) analyses performed on the population revealed genomic regions associated with several traits, including the agronomically important time to flowering (tf), alkaloid synthesis and stem height (Ph). Use of HRM-STS markers also allowed us to make direct comparisons between our map and that of the related crop, Lupinus angustifolius, based on the conversion of RFLP, microsatellite and single nucleotide polymorphism (SNP) markers into HRM markers.

Flory-Stockmayer analysis on reprocessable polymer networks

NASA Astrophysics Data System (ADS)

Li, Lingqiao; Chen, Xi; Jin, Kailong; Torkelson, John

Reprocessable polymer networks can undergo structure rearrangement through dynamic chemistries under proper conditions, making them a promising candidate for recyclable crosslinked materials, e.g. tires. This research field has been focusing on various chemistries. However, there has been lacking of an essential physical theory explaining the relationship between abundancy of dynamic linkages and reprocessability. Based on the classical Flory-Stockmayer analysis on network gelation, we developed a similar analysis on reprocessable polymer networks to quantitatively predict the critical condition for reprocessability. Our theory indicates that it is unnecessary for all bonds to be dynamic to make the resulting network reprocessable. As long as there is no percolated permanent network in the system, the material can fully rearrange. To experimentally validate our theory, we used a thiol-epoxy network model system with various dynamic linkage compositions. The stress relaxation behavior of resulting materials supports our theoretical prediction: only 50 % of linkages between crosslinks need to be dynamic for a tri-arm network to be reprocessable. Therefore, this analysis provides the first fundamental theoretical platform for designing and evaluating reprocessable polymer networks. We thank McCormick Research Catalyst Award Fund and ISEN cluster fellowship (L. L.) for funding support.

Autosomal Linkage Scan for Loci Predisposing to Comorbid Dependence on Multiple Substances

PubMed Central

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R.; Farrer, Lindsay A.; Elston, Robert C.; Gelernter, Joel

2014-01-01

Multiple substance dependence (MSD) trait comorbidity is common, and MSD patients are often severely affected clinically. While shared genetic risks have been documented, so far there has been no published report using the linkage scan approach to survey risk loci for MSD as a phenotype. A total of 1,758 individuals in 739 families [384 African American (AA) and 355 European American (EA) families] ascertained via affected sib-pairs with cocaine or opioid or alcohol dependence were genotyped using an array-based linkage panel of single-nucleotide polymorphism markers. Fuzzy clustering analysis was conducted on individuals with alcohol, cannabis, cocaine, opioid, and nicotine dependence for AAs and EAs separately, and linkage scans were conducted for the output membership coefficients using Merlin-regression. In EAs, we observed an autosome-wide significant linkage signal on chromosome 4 (peak lod = 3.31 at 68.3 cM; empirical autosome-wide P = 0.038), and a suggestive linkage signal on chromosome 21 (peak lod = 2.37 at 19.4 cM). In AAs, four suggestive linkage peaks were observed: two peaks on chromosome 10 (lod = 2.66 at 96.7 cM and lod = 3.02 at 147.6 cM] and the other two on chromosomes 3 (lod = 2.81 at 145.5 cM) and 9 (lod = 1.93 at 146.8 cM). Three particularly promising candidate genes, GABRA4, GABRB1, and CLOCK, are located within or very close to the autosome-wide significant linkage region for EAs on chromosome 4. This is the first linkage evidence supporting existence of genetic loci influencing risk for several comorbid disorders simultaneously in two major US populations. PMID:22354695

A spin column-free approach to sodium hydroxide-based glycan permethylation.

PubMed

Hu, Yueming; Borges, Chad R

2017-07-24

Glycan permethylation was introduced as a tool to facilitate the study of glycans in 1903. Since that time, permethylation procedures have been continually modified to improve permethylation efficiency and qualitative applicability. Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues-yields which were comparable to (or better than) those of some widely-used spin column-based procedures. A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based "glycan node" analysis results. When applied to blood plasma samples from stage III-IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens.

A spin column-free approach to sodium hydroxide-based glycan permethylation†

PubMed Central

Hu, Yueming; Borges, Chad R.

2018-01-01

Glycan permethylation was introduced as a tool to facilitate the study of glycans in 1903. Since that time, permethylation procedures have been continually modified to improve permethylation efficiency and qualitative applicability. Typically, however, either laborious preparation steps or cumbersome and uneconomical spin columns have been needed to obtain decent permethylation yields on small glycan samples. Here we describe a spin column-free (SCF) glycan permethylation procedure that is applicable to both O- and N-linked glycans and can be employed upstream to intact glycan analysis by MALDI-MS, ESI-MS, or glycan linkage analysis by GC-MS. The SCF procedure involves neutralization of NaOH beads by acidified phosphate buffer, which eliminates the risk of glycan oxidative degradation and avoids the use of spin columns. Optimization of the new permethylation procedure provided high permethylation efficiency for both hexose (>98%) and HexNAc (>99%) residues—yields which were comparable to (or better than) those of some widely-used spin column-based procedures. A light vs. heavy labelling approach was employed to compare intact glycan yields from a popular spin-column based approach to the SCF approach. Recovery of intact N-glycans was significantly better with the SCF procedure (p < 0.05), but overall yield of O-glycans was similar or slightly diminished (p < 0.05 for tetrasaccharides or smaller). When the SCF procedure was employed upstream to hydrolysis, reduction and acetylation for glycan linkage analysis of pooled glycans from unfractionated blood plasma, analytical reproducibility was on par with that from previous spin column-based “glycan node” analysis results. When applied to blood plasma samples from stage III–IV breast cancer patients (n = 20) and age-matched controls (n = 20), the SCF procedure facilitated identification of three glycan nodes with significantly different distributions between the cases and controls (ROC c-statistics > 0.75; p < 0.01). In summary, the SCF permethylation procedure expedites and economizes both intact glycan analysis and linkage analysis of glycans from whole biospecimens. PMID:28635997

Meta-analysis of genome-wide scans for blood pressure in African American and Nigerian samples. The National Heart, Lung, and Blood Institute GeneLink Project.

PubMed

Rice, Treva; Cooper, Richard S; Wu, Xiaodong; Bouchard, Claude; Rankinen, Tuomo; Rao, D C; Jaquish, Cashell E; Fabsitz, Richard R; Province, Michael A

2006-03-01

In many genetic studies of complex traits, sample sizes are often too small to detect linkages of low-to-moderate effects. However, the combined linkage evidence across several studies can be synthesized using meta-analysis with the aim of providing more definitive support of linkage. In the current study using the National Heart, Lung, and Blood Institute (NHLBI) GeneLink Project, a meta-analysis based on a modification of Fisher's method of pooling P values was used to investigate linkage for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values across three studies involving African American and Nigerian families (HyperGEN, Health, Risk Factors, Exercise Training and Genetics [HERITAGE], and Genetics of Hypertension in Blacks). The meta results suggest two regions (2p and 7p) provide enhanced linkage evidence compared with the individual study results. The maximal meta Lod score of 2.9 on 2p14-p13.1 (64-78 cM) represented approximately 1-Lod unit increase over the respective individual study scores. This general region has been implicated previously involving primarily families of white ethnicity and provides confirmatory evidence that this QTL is common across ethnic groups. The second finding at 7p21.3-p15.3 (8-25 cM) provided a meta Lod of 3.5. Although region was implicated primarily in the Nigerian subjects the low-level but consistent support involving the African American families (individual Lod score of 1.0) suggests a novel QTL with respect to BP variation in individuals of black ethnicity. Follow-up studies involving positional cloning efforts of the combined families showing linkage evidence in these regions (particularly 2p) may be warranted to verify these findings and identify the genes and causative variants.

Phase-Division-Based Dynamic Optimization of Linkages for Drawing Servo Presses

NASA Astrophysics Data System (ADS)

Zhang, Zhi-Gang; Wang, Li-Ping; Cao, Yan-Ke

2017-11-01

Existing linkage-optimization methods are designed for mechanical presses; few can be directly used for servo presses, so development of the servo press is limited. Based on the complementarity of linkage optimization and motion planning, a phase-division-based linkage-optimization model for a drawing servo press is established. Considering the motion-planning principles of a drawing servo press, and taking account of work rating and efficiency, the constraints of the optimization model are constructed. Linkage is optimized in two modes: use of either constant eccentric speed or constant slide speed in the work segments. The performances of optimized linkages are compared with those of a mature linkage SL4-2000A, which is optimized by a traditional method. The results show that the work rating of a drawing servo press equipped with linkages optimized by this new method improved and the root-mean-square torque of the servo motors is reduced by more than 10%. This research provides a promising method for designing energy-saving drawing servo presses with high work ratings.

Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis.

PubMed

Todhunter, Rory J; Casella, George; Bliss, Stuart P; Lust, George; Williams, Alma Jo; Hamilton, Samuel; Dykes, Nathan L; Yeager, Amy E; Gilbert, Robert O; Burton-Wurster, Nancy I; Mellersh, Cathryn C; Acland, Gregory M

2003-04-01

To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree. 147 Labrador Retrievers, Greyhounds, and their crossbreed offspring. Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined. For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.

An ultra-high density linkage map and QTL mapping for sex and growth-related traits of common carp (Cyprinus carpio)

PubMed Central

Peng, Wenzhu; Xu, Jian; Zhang, Yan; Feng, Jianxin; Dong, Chuanju; Jiang, Likun; Feng, Jingyan; Chen, Baohua; Gong, Yiwen; Chen, Lin; Xu, Peng

2016-01-01

High density genetic linkage maps are essential for QTL fine mapping, comparative genomics and high quality genome sequence assembly. In this study, we constructed a high-density and high-resolution genetic linkage map with 28,194 SNP markers on 14,146 distinct loci for common carp based on high-throughput genotyping with the carp 250 K single nucleotide polymorphism (SNP) array in a mapping family. The genetic length of the consensus map was 10,595.94 cM with an average locus interval of 0.75 cM and an average marker interval of 0.38 cM. Comparative genomic analysis revealed high level of conserved syntenies between common carp and the closely related model species zebrafish and medaka. The genome scaffolds were anchored to the high-density linkage map, spanning 1,357 Mb of common carp reference genome. QTL mapping and association analysis identified 22 QTLs for growth-related traits and 7 QTLs for sex dimorphism. Candidate genes underlying growth-related traits were identified, including important regulators such as KISS2, IGF1, SMTLB, NPFFR1 and CPE. Candidate genes associated with sex dimorphism were also identified including 3KSR and DMRT2b. The high-density and high-resolution genetic linkage map provides an important tool for QTL fine mapping and positional cloning of economically important traits, and improving common carp genome assembly. PMID:27225429

Barriers and facilitators of linkage to HIV care among HIV-infected young Chinese men who have sex with men: a qualitative study.

PubMed

Li, Haochu; Wei, Chongyi; Tucker, Joseph; Kang, Dianmin; Liao, Meizhen; Holroyd, Eleanor; Zheng, Jietao; Qi, Qian; Ma, Wei

2017-03-16

The Four Free and One Care Policy (HIV/AIDS-related free services) has been in place in China since 2004. However, linkage to human immunodeficiency virus (HIV) care is not yet achieved very well among people living with HIV. We conducted a qualitative study to explore individual and contextual factors that may influence a linkage to HIV care from the perspective of young HIV-infected men who have sex with men (MSM) in a highly centralized HIV care context of China. Purposive sampling was used to recruit 21 HIV-infected MSM in Shandong Province, with in-depth interviews conducted between March and July 2015. Thematic content analysis was subsequently used for data analysis. Key barriers and facilitators related to a linkage to HIV care emerged from participants' narratives. The barriers included perceived healthy status, low health literacy, and stigma associated with receiving HIV care. The facilitators included an awareness of responsibility, knowledge associated with health literacy, social support, and trusting and relying on services provided by the Center for Disease Control and Prevention (CDC) and the government. These were related to the quality of current HIV counselling and testing, service promotion, and the cost and placement of these HIV services. In order to improve the MSM linkage to HIV care in China, it is imperative to improve the quality of the current on-going counselling and testing. Further critical linkage support includes increasing supportive services among local CDC systems, designated hospitals and community-based organizations (CBOs), and more financial support for HIV/AIDS related testing, medical checkups and treatments.

Conclusion of LOD-score analysis for family data generated under two-locus models.

PubMed Central

Dizier, M. H.; Babron, M. C.; Clerget-Darpoux, F.

1996-01-01

The power to detect linkage by the LOD-score method is investigated here for diseases that depend on the effects of two genes. The classical strategy is, first, to detect a major-gene (MG) effect by segregation analysis and, second, to seek for linkage with genetic markers by the LOD-score method using the MG parameters. We already showed that segregation analysis can lead to evidence for a MG effect for many two-locus models, with the estimates of the MG parameters being very different from those of the two genes involved in the disease. We show here that use of these MG parameter estimates in the LOD-score analysis may lead to a failure to detect linkage for some two-locus models. For these models, use of the sib-pair method gives a non-negligible increase of power to detect linkage. The linkage-homogeneity test among subsamples differing for the familial disease distribution provides evidence of parameter misspecification, when the MG parameters are used. Moreover, for most of the models, use of the MG parameters in LOD-score analysis leads to a large bias in estimation of the recombination fraction and sometimes also to a rejection of linkage for the true recombination fraction. A final important point is that a strong evidence of an MG effect, obtained by segregation analysis, does not necessarily imply that linkage will be detected for at least one of the two genes, even with the true parameters and with a close informative marker. PMID:8651311

Meta-analysis of 32 genome-wide linkage studies of schizophrenia

PubMed Central

Ng, MYM; Levinson, DF; Faraone, SV; Suarez, BK; DeLisi, LE; Arinami, T; Riley, B; Paunio, T; Pulver, AE; Irmansyah; Holmans, PA; Escamilla, M; Wildenauer, DB; Williams, NM; Laurent, C; Mowry, BJ; Brzustowicz, LM; Maziade, M; Sklar, P; Garver, DL; Abecasis, GR; Lerer, B; Fallin, MD; Gurling, HMD; Gejman, PV; Lindholm, E; Moises, HW; Byerley, W; Wijsman, EM; Forabosco, P; Tsuang, MT; Hwu, H-G; Okazaki, Y; Kendler, KS; Wormley, B; Fanous, A; Walsh, D; O’Neill, FA; Peltonen, L; Nestadt, G; Lasseter, VK; Liang, KY; Papadimitriou, GM; Dikeos, DG; Schwab, SG; Owen, MJ; O’Donovan, MC; Norton, N; Hare, E; Raventos, H; Nicolini, H; Albus, M; Maier, W; Nimgaonkar, VL; Terenius, L; Mallet, J; Jay, M; Godard, S; Nertney, D; Alexander, M; Crowe, RR; Silverman, JM; Bassett, AS; Roy, M-A; Mérette, C; Pato, CN; Pato, MT; Roos, J Louw; Kohn, Y; Amann-Zalcenstein, D; Kalsi, G; McQuillin, A; Curtis, D; Brynjolfson, J; Sigmundsson, T; Petursson, H; Sanders, AR; Duan, J; Jazin, E; Myles-Worsley, M; Karayiorgou, M; Lewis, CM

2009-01-01

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (PSR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for ‘aggregate’ genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. PMID:19349958

Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB).

PubMed

Berger, W; van Duijnhoven, G; Pinckers, A; Smits, A; Ropers, H H; Cremers, F

1995-01-01

Linkage analysis has been performed in a large Dutch pedigree with X-linked recessive congenital stationary night blindness (CSNB) by utilizing 16 DNA markers from the proximal short arm of the human X chromosome (Xp21.1-11.2). Thirteen polymorphic markers are at least partially informative and have enabled pairwise and multipoint linkage analysis. For three loci, i.e. DXS228, the monoamine oxidase B gene and the Norrie disease gene (NDG), multipoint linkage studies have yielded maximum lod scores of > 3.0 at a recombination fraction of zero. Analysis of recombination events has enabled us to rule out the possibility that the underlying defect in this family is allelic to RP3; the gene defect could also be excluded from the proximal part of the region known to carry RP2. Linkage data are consistent with a possible involvement of the NDG but mutations in the open reading frame of this gene have not been found.

Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia

PubMed Central

Lewis, Cathryn M.; Levinson, Douglas F.; Wise, Lesley H.; DeLisi, Lynn E.; Straub, Richard E.; Hovatta, Iiris; Williams, Nigel M.; Schwab, Sibylle G.; Pulver, Ann E.; Faraone, Stephen V.; Brzustowicz, Linda M.; Kaufmann, Charles A.; Garver, David L.; Gurling, Hugh M. D.; Lindholm, Eva; Coon, Hilary; Moises, Hans W.; Byerley, William; Shaw, Sarah H.; Mesen, Andrea; Sherrington, Robin; O’Neill, F. Anthony; Walsh, Dermot; Kendler, Kenneth S.; Ekelund, Jesper; Paunio, Tiina; Lönnqvist, Jouko; Peltonen, Leena; O’Donovan, Michael C.; Owen, Michael J.; Wildenauer, Dieter B.; Maier, Wolfgang; Nestadt, Gerald; Blouin, Jean-Louis; Antonarakis, Stylianos E.; Mowry, Bryan J.; Silverman, Jeremy M.; Crowe, Raymond R.; Cloninger, C. Robert; Tsuang, Ming T.; Malaspina, Dolores; Harkavy-Friedman, Jill M.; Svrakic, Dragan M.; Bassett, Anne S.; Holcomb, Jennifer; Kalsi, Gursharan; McQuillin, Andrew; Brynjolfson, Jon; Sigmundsson, Thordur; Petursson, Hannes; Jazin, Elena; Zoëga, Tomas; Helgason, Tomas

2003-01-01

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (Ravg) and then weighted for sample size (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}\\sqrt{N[affected cases]}\\end{equation*}\\end{document}). A permutation test was used to compute the probability of observing, by chance, each bin’s average rank (PAvgRnk) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (Pord). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both PAvgRnk and Pord<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with Pord<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations. PMID:12802786

Genetic Studies of Stuttering in a Founder Population

PubMed Central

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 with nominal evidence for linkage were found on chromosomes 3 (P=0.013, 208.8 centiMorgans (cM)), 13 (P=0.012, 52.6 cM), and 15 (P=0.02, 100 cM). Regions with nominal evidence for association with stuttering that overlapped with a linkage signal are located on chromosomes 3 (P=0.0047, 195 cM), 9 (P=0.0067, 46.5 cM), and 13 (P=0.0055, 52.6 cM). We also conducted the first meta-analysis for stuttering using results from linkage studies in the Hutterites and The Illinois International Genetics of Stuttering Project and identified regions with nominal evidence for linkage on chromosomes 2 (P=0.013, 180–195 cM) and 5 (P=0.0051, 105–120 cM; P=0.015, 120–135 cM). None of the linkage signals detected in the Hutterite sample alone, or in the meta-analysis, meet genome-wide criteria for significance, although some of the stronger signals overlap linkage mapping signals previously reported for other speech and language disorders. PMID:17276504

Population genetic analysis of Enterocytozoon bieneusi in humans.

PubMed

Li, Wei; Cama, Vitaliano; Feng, Yaoyu; Gilman, Robert H; Bern, Caryn; Zhang, Xichen; Xiao, Lihua

2012-01-01

Genotyping based on sequence analysis of the ribosomal internal transcribed spacer has revealed significant genetic diversity in Enterocytozoonbieneusi. Thus far, the population genetics of E. bieneusi and its significance in the epidemiology of microsporidiosis have not been examined. In this study, a multilocus sequence typing of E. bieneusi in AIDS patients in Lima, Peru was conducted, using 72 specimens previously genotyped as A, D, IV, EbpC, WL11, Peru7, Peru8, Peru10 and Peru11 at the internal transcribed spacer locus. Altogether, 39 multilocus genotypes were identified among the 72 specimens. The observation of strong intragenic linkage disequilibria and limited genetic recombination among markers were indicative of an overall clonal population structure of E. bieneusi. Measures of pair-wise intergenic linkage disequilibria and a standardised index of association (IAS) based on allelic profile data further supported this conclusion. Both sequence-based and allelic profile-based phylogenetic analyses showed the presence of two genetically isolated groups in the study population, one (group 1) containing isolates of the anthroponotic internal transcribed spacer genotype A, and the other (group 2) containing isolates of multiple internal transcribed spacer genotypes (mainly genotypes D and IV) with zoonotic potential. The measurement of linkage disequilibria and recombination indicated group 2 had a clonal population structure, whereas group 1 had an epidemic population structure. The formation of the two sub-populations was confirmed by STRUCTURE and Wright's fixation index (FST) analyses. The data highlight the power of MLST in understanding the epidemiology of E. bieneusi. Published by Elsevier Ltd.

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

PubMed Central

2010-01-01

Background The inability of aspirin (ASA) to adequately suppress platelet aggregation is associated with future risk of coronary artery disease (CAD). Heritability studies of agonist-induced platelet function phenotypes suggest that genetic variation may be responsible for ASA responsiveness. In this study, we leverage independent information from genome-wide linkage and association data to determine loci controlling platelet phenotypes before and after treatment with ASA. Methods Clinical data on 37 agonist-induced platelet function phenotypes were evaluated before and after a 2-week trial of ASA (81 mg/day) in 1231 European American and 846 African American healthy subjects with a family history of premature CAD. Principal component analysis was performed to minimize the number of independent factors underlying the covariance of these various phenotypes. Multi-point sib-pair based linkage analysis was performed using a microsatellite marker set, and single-SNP association tests were performed using markers from the Illumina 1 M genotyping chip from deCODE Genetics, Inc. All analyses were performed separately within each ethnic group. Results Several genomic regions appear to be linked to ASA response factors: a 10 cM region in African Americans on chromosome 5q11.2 had several STRs with suggestive (p-value < 7 × 10-4) and significant (p-value < 2 × 10-5) linkage to post aspirin platelet response to ADP, and ten additional factors had suggestive evidence for linkage (p-value < 7 × 10-4) to thirteen genomic regions. All but one of these factors were aspirin response variables. While the strength of genome-wide SNP association signals for factors showing evidence for linkage is limited, especially at the strict thresholds of genome-wide criteria (N = 9 SNPs for 11 factors), more signals were considered significant when the association signal was weighted by evidence for linkage (N = 30 SNPs). Conclusions Our study supports the hypothesis that platelet phenotypes in response to ASA likely have genetic control and the combined approach of linkage and association offers an alternative approach to prioritizing regions of interest for subsequent follow-up. PMID:20529293

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

PubMed

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.

Significant linkage to airway responsiveness on chromosome 12q24 in families of children with asthma in Costa Rica.

PubMed

Celedón, Juan C; Soto-Quiros, Manuel E; Avila, Lydiana; Lake, Stephen L; Liang, Catherine; Fournier, Eduardo; Spesny, Mitzi; Hersh, Craig P; Sylvia, Jody S; Hudson, Thomas J; Verner, Andrei; Klanderman, Barbara J; Freimer, Nelson B; Silverman, Edwin K; Weiss, Scott T

2007-01-01

Although asthma is a major public health problem in certain Hispanic subgroups in the United States and Latin America, only one genome scan for asthma has included Hispanic individuals. Because of small sample size, that study had limited statistical power to detect linkage to asthma and its intermediate phenotypes in Hispanic participants. To identify genomic regions that contain susceptibility genes for asthma and airway responsiveness in an isolated Hispanic population living in the Central Valley of Costa Rica, we conducted a genome-wide linkage analysis of asthma (n = 638) and airway responsiveness (n = 488) in members of eight large pedigrees of Costa Rican children with asthma. Nonparametric multipoint linkage analysis of asthma was conducted by the NPL-PAIR allele-sharing statistic, and variance component models were used for the multipoint linkage analysis of airway responsiveness as a quantitative phenotype. All linkage analyses were repeated after exclusion of the phenotypic data of former and current smokers. Chromosome 12q showed some evidence of linkage to asthma, particularly in nonsmokers (P < 0.01). Among nonsmokers, there was suggestive evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 2.33 at 146 cM). After genotyping 18 additional short-tandem repeat markers on chromosome 12q, there was significant evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 3.79 at 144 cM), with a relatively narrow 1.5-LOD unit support interval for the observed linkage peak (142-147 cM). Our results suggest that chromosome 12q24.31 contains a locus (or loci) that influence a critical intermediate phenotype of asthma (airway responsiveness) in Costa Ricans.

Bridging the gap between genome analysis and precision breeding in potato.

PubMed

Gebhardt, Christiane

2013-04-01

Efficiency and precision in plant breeding can be enhanced by using diagnostic DNA-based markers for the selection of superior cultivars. This technique has been applied to many crops, including potatoes. The first generation of diagnostic DNA-based markers useful in potato breeding were enabled by several developments: genetic linkage maps based on DNA polymorphisms, linkage mapping of qualitative and quantitative agronomic traits, cloning and functional analysis of genes for pathogen resistance and genes controlling plant metabolism, and association genetics in collections of tetraploid varieties and advanced breeding clones. Although these have led to significant improvements in potato genetics, the prediction of most, if not all, natural variation in agronomic traits by diagnostic markers ultimately requires the identification of the causal genes and their allelic variants. This objective will be facilitated by new genomic tools, such as genomic resequencing and comparative profiling of the proteome, transcriptome, and metabolome in combination with phenotyping genetic materials relevant for variety development. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fine Mapping on Chromosome 13q32–34 and Brain Expression Analysis Implicates MYO16 in Schizophrenia

PubMed Central

Rodriguez-Murillo, Laura; Xu, Bin; Roos, J Louw; Abecasis, Gonçalo R; Gogos, Joseph A; Karayiorgou, Maria

2014-01-01

We previously reported linkage of schizophrenia and schizoaffective disorder to 13q32–34 in the European descent Afrikaner population from South Africa. The nature of genetic variation underlying linkage peaks in psychiatric disorders remains largely unknown and both rare and common variants may be contributing. Here, we examine the contribution of common variants located under the 13q32–34 linkage region. We used densely spaced SNPs to fine map the linkage peak region using both a discovery sample of 415 families and a meta-analysis incorporating two additional replication family samples. In a second phase of the study, we use one family-based data set with 237 families and independent case–control data sets for fine mapping of the common variant association signal using HapMap SNPs. We report a significant association with a genetic variant (rs9583277) within the gene encoding for the myosin heavy-chain Myr 8 (MYO16), which has been implicated in neuronal phosphoinositide 3-kinase signaling. Follow-up analysis of HapMap variation within MYO16 in a second set of Afrikaner families and additional case–control data sets of European descent highlighted a region across introns 2–6 as the most likely region to harbor common MYO16 risk variants. Expression analysis revealed a significant increase in the level of MYO16 expression in the brains of schizophrenia patients. Our results suggest that common variation within MYO16 may contribute to the genetic liability to schizophrenia. PMID:24141571

Linking HIV-Negative Youth to Prevention Services in 12 U.S. Cities: Barriers and Facilitators to Implementing the HIV Prevention Continuum.

PubMed

Doll, Mimi; Fortenberry, J Dennis; Roseland, Denise; McAuliff, Kathleen; Wilson, Craig M; Boyer, Cherrie B

2018-04-01

Linkage of HIV-negative youth to prevention services is increasingly important with the development of effective pre-exposure prophylaxis that complements behavioral and other prevention-focused interventions. However, effective infrastructure for delivery of prevention services does not exist, leaving many programs to address HIV prevention without data to guide program development/implementation. The objective of this study was to provide a qualitative description of barriers and facilitators of linkage to prevention services among high-risk, HIV-negative youth. Thematic analysis of structured interviews with staff implementing linkage to prevention services programs for youth aged 12-24 years. Twelve adolescent medicine HIV primary care programs as part of larger testing research program focused on young sexual minority men of color. The study included staff implementing linkage to prevention services programs along with community-based HIV testing programs. The main outcomes of the study were key barriers/facilitators to linkage to prevention services. Eight themes summarized perspectives on linkage to prevention services: (1) relationships with community partners, (2) trust between providers and youth, (3) youth capacity to navigate prevention services, (4) pre-exposure prophylaxis specific issues, (5) privacy issues, (6) gaps in health records preventing tailored services, (7) confidentiality of care for youth accessing services through parents'/caretakers' insurance, and (8) need for health-care institutions to keep pace with models that prioritize HIV prevention among at-risk youth. Themes are discussed in the context of factors that facilitated/challenged linkage to prevention services. Several evidence-based HIV prevention tools are available; infrastructures for coordinated service delivery to high-risk youth have not been developed. Implementation of such infrastructures requires attention to community-, provider-, and youth-related issues. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Rapid genotyping with DNA micro-arrays for high-density linkage mapping and QTL mapping in common buckwheat (Fagopyrum esculentum Moench)

PubMed Central

Yabe, Shiori; Hara, Takashi; Ueno, Mariko; Enoki, Hiroyuki; Kimura, Tatsuro; Nishimura, Satoru; Yasui, Yasuo; Ohsawa, Ryo; Iwata, Hiroyoshi

2014-01-01

For genetic studies and genomics-assisted breeding, particularly of minor crops, a genotyping system that does not require a priori genomic information is preferable. Here, we demonstrated the potential of a novel array-based genotyping system for the rapid construction of high-density linkage map and quantitative trait loci (QTL) mapping. By using the system, we successfully constructed an accurate, high-density linkage map for common buckwheat (Fagopyrum esculentum Moench); the map was composed of 756 loci and included 8,884 markers. The number of linkage groups converged to eight, which is the basic number of chromosomes in common buckwheat. The sizes of the linkage groups of the P1 and P2 maps were 773.8 and 800.4 cM, respectively. The average interval between adjacent loci was 2.13 cM. The linkage map constructed here will be useful for the analysis of other common buckwheat populations. We also performed QTL mapping for main stem length and detected four QTL. It took 37 days to process 178 samples from DNA extraction to genotyping, indicating the system enables genotyping of genome-wide markers for a few hundred buckwheat plants before the plants mature. The novel system will be useful for genomics-assisted breeding in minor crops without a priori genomic information. PMID:25914583

Rapid genotyping with DNA micro-arrays for high-density linkage mapping and QTL mapping in common buckwheat (Fagopyrum esculentum Moench).

PubMed

Yabe, Shiori; Hara, Takashi; Ueno, Mariko; Enoki, Hiroyuki; Kimura, Tatsuro; Nishimura, Satoru; Yasui, Yasuo; Ohsawa, Ryo; Iwata, Hiroyoshi

2014-12-01

For genetic studies and genomics-assisted breeding, particularly of minor crops, a genotyping system that does not require a priori genomic information is preferable. Here, we demonstrated the potential of a novel array-based genotyping system for the rapid construction of high-density linkage map and quantitative trait loci (QTL) mapping. By using the system, we successfully constructed an accurate, high-density linkage map for common buckwheat (Fagopyrum esculentum Moench); the map was composed of 756 loci and included 8,884 markers. The number of linkage groups converged to eight, which is the basic number of chromosomes in common buckwheat. The sizes of the linkage groups of the P1 and P2 maps were 773.8 and 800.4 cM, respectively. The average interval between adjacent loci was 2.13 cM. The linkage map constructed here will be useful for the analysis of other common buckwheat populations. We also performed QTL mapping for main stem length and detected four QTL. It took 37 days to process 178 samples from DNA extraction to genotyping, indicating the system enables genotyping of genome-wide markers for a few hundred buckwheat plants before the plants mature. The novel system will be useful for genomics-assisted breeding in minor crops without a priori genomic information.

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study

PubMed Central

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-01-01

Background High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Results Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Conclusion Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions. PMID:14975161

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study.

PubMed

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-12-31

High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions.

Genetic linkage map and comparative genome analysis for the estuarine Atlantic killifish (Fundulus heteroclitus)

EPA Pesticide Factsheets

Genetic linkage maps are valuable tools in evolutionary biology; however, their availability for wild populations is extremely limited. Fundulus heteroclitus (Atlantic killifish) is a non-migratory estuarine fish that exhibits high allelic and phenotypic diversity partitioned among subpopulations that reside in disparate environmental conditions. An ideal candidate model organism for studying gene-environment interactions, the molecular toolbox for F. heteroclitus is limited. We identified hundreds of novel microsatellites which, when combined with existing microsatellites and single nucleotide polymorphisms (SNPs), were used to construct the first genetic linkage map for this species. By integrating independent linkage maps from three genetic crosses, we developed a consensus map containing 24 linkage groups, consistent with the number of chromosomes reported for this species. These linkage groups span 2300 centimorgans (cM) of recombinant genomic space, intermediate in size relative to the current linkage maps for the teleosts, medaka and zebrafish. Comparisons between fish genomes support a high degree of synteny between the consensus F. heteroclitus linkage map and the medaka and (to a lesser extent) zebrafish physical genome assemblies.This dataset is associated with the following publication:Waits , E., J. Martinson , B. Rinner, S. Morris, D. Proestou, D. Champlin , and D. Nacci. Genetic linkage map and comparative genome analysis for the estuarine Atlanti

Non-coding genomic regions possessing enhancer and silencer potential are associated with healthy aging and exceptional survival.

PubMed

Kim, Sangkyu; Welsh, David A; Myers, Leann; Cherry, Katie E; Wyckoff, Jennifer; Jazwinski, S Michal

2015-02-28

We have completed a genome-wide linkage scan for healthy aging using data collected from a family study, followed by fine-mapping by association in a separate population, the first such attempt reported. The family cohort consisted of parents of age 90 or above and their children ranging in age from 50 to 80. As a quantitative measure of healthy aging, we used a frailty index, called FI34, based on 34 health and function variables. The linkage scan found a single significant linkage peak on chromosome 12. Using an independent cohort of unrelated nonagenarians, we carried out a fine-scale association mapping of the region suggestive of linkage and identified three sites associated with healthy aging. These healthy-aging sites (HASs) are located in intergenic regions at 12q13-14. HAS-1 has been previously associated with multiple diseases, and an enhancer was recently mapped and experimentally validated within the site. HAS-2 is a previously uncharacterized site possessing genomic features suggestive of enhancer activity. HAS-3 contains features associated with Polycomb repression. The HASs also contain variants associated with exceptional longevity, based on a separate analysis. Our results provide insight into functional genomic networks involving non-coding regulatory elements that are involved in healthy aging and longevity.

Non-coding genomic regions possessing enhancer and silencer potential are associated with healthy aging and exceptional survival

PubMed Central

Kim, Sangkyu; Welsh, David A.; Myers, Leann; Cherry, Katie E.; Wyckoff, Jennifer; Jazwinski, S. Michal

2015-01-01

We have completed a genome-wide linkage scan for healthy aging using data collected from a family study, followed by fine-mapping by association in a separate population, the first such attempt reported. The family cohort consisted of parents of age 90 or above and their children ranging in age from 50 to 80. As a quantitative measure of healthy aging, we used a frailty index, called FI34, based on 34 health and function variables. The linkage scan found a single significant linkage peak on chromosome 12. Using an independent cohort of unrelated nonagenarians, we carried out a fine-scale association mapping of the region suggestive of linkage and identified three sites associated with healthy aging. These healthy-aging sites (HASs) are located in intergenic regions at 12q13–14. HAS-1 has been previously associated with multiple diseases, and an enhancer was recently mapped and experimentally validated within the site. HAS-2 is a previously uncharacterized site possessing genomic features suggestive of enhancer activity. HAS-3 contains features associated with Polycomb repression. The HASs also contain variants associated with exceptional longevity, based on a separate analysis. Our results provide insight into functional genomic networks involving non-coding regulatory elements that are involved in healthy aging and longevity. PMID:25682868

Clinical Application of an Innovative Multiplex-Fluorescent-Labeled STRs Assay for Prader-Willi Syndrome and Angelman Syndrome.

PubMed

Zhang, Kaihui; Liu, Shu; Feng, Bing; Yang, Yali; Zhang, Haiyan; Dong, Rui; Liu, Yi; Gai, Zhongtao

2016-01-01

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chr15q11.2-q13.3. Three mechanisms are known to be involved in the pathogenesis: microdeletions, uniparental disomy (UPD) and imprinting defects. Both disorders are difficult to be definitely diagnosed at early age if no available molecular cytogenetic tests. In this study, we identified 5 AS patients with the maternal deletion and 26 PWS patients with paternal deletion on chr15q11-q13 by using an innovative multiplex-fluorescent-labeled short tandem repeats (STRs) assay based on linkage analysis, and validated by the methylation-specific PCR and array comparative genomic hybridization techniques. More interesting, one of these PWS patients was confirmed as maternal uniparental isodisomy by the STR linkage analysis. The phenotypic and genotypic characteristics of these individuals were also presented. Our results indicate that the new linkage analysis is much faster and easier for large-scale screening deletion and uniparental disomy, thus providing a valuable method for early diagnosis of PWS/AS patients, which is critical for genetic diagnosis, management and improvement of prognosis.

Clinical Application of an Innovative Multiplex-Fluorescent-Labeled STRs Assay for Prader-Willi Syndrome and Angelman Syndrome

PubMed Central

Feng, Bing; Yang, Yali; Zhang, Haiyan; Dong, Rui; Liu, Yi; Gai, Zhongtao

2016-01-01

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chr15q11.2-q13.3. Three mechanisms are known to be involved in the pathogenesis: microdeletions, uniparental disomy (UPD) and imprinting defects. Both disorders are difficult to be definitely diagnosed at early age if no available molecular cytogenetic tests. In this study, we identified 5 AS patients with the maternal deletion and 26 PWS patients with paternal deletion on chr15q11-q13 by using an innovative multiplex-fluorescent-labeled short tandem repeats (STRs) assay based on linkage analysis, and validated by the methylation-specific PCR and array comparative genomic hybridization techniques. More interesting, one of these PWS patients was confirmed as maternal uniparental isodisomy by the STR linkage analysis. The phenotypic and genotypic characteristics of these individuals were also presented. Our results indicate that the new linkage analysis is much faster and easier for large-scale screening deletion and uniparental disomy, thus providing a valuable method for early diagnosis of PWS/AS patients, which is critical for genetic diagnosis, management and improvement of prognosis. PMID:26841067

Smoothing of the bivariate LOD score for non-normal quantitative traits.

PubMed

Buil, Alfonso; Dyer, Thomas D; Almasy, Laura; Blangero, John

2005-12-30

Variance component analysis provides an efficient method for performing linkage analysis for quantitative traits. However, type I error of variance components-based likelihood ratio testing may be affected when phenotypic data are non-normally distributed (especially with high values of kurtosis). This results in inflated LOD scores when the normality assumption does not hold. Even though different solutions have been proposed to deal with this problem with univariate phenotypes, little work has been done in the multivariate case. We present an empirical approach to adjust the inflated LOD scores obtained from a bivariate phenotype that violates the assumption of normality. Using the Collaborative Study on the Genetics of Alcoholism data available for the Genetic Analysis Workshop 14, we show how bivariate linkage analysis with leptokurtotic traits gives an inflated type I error. We perform a novel correction that achieves acceptable levels of type I error.

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

PubMed

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

2017-04-04

Cultivated spinach (Spinacia oleracea L.) is one of the most widely cultivated types of leafy vegetable in the world, and it has a high nutritional value. Spinach is also an ideal plant for investigating the mechanism of sex determination because it is a dioecious species with separate male and female plants. Some reports on the sex labeling and localization of spinach in the study of molecular markers have surfaced. However, there have only been two reports completed on the genetic map of spinach. The lack of rich and reliable molecular markers and the shortage of high-density linkage maps are important constraints in spinach research work. In this study, a high-density genetic map of spinach based on the Specific-locus Amplified Fragment Sequencing (SLAF-seq) technique was constructed; the sex-determining gene was also finely mapped. Through bio-information analysis, 50.75 Gb of data in total was obtained, including 207.58 million paired-end reads. Finally, 145,456 high-quality SLAF markers were obtained, with 27,800 polymorphic markers and 4080 SLAF markers were finally mapped onto the genetic map after linkage analysis. The map spanned 1,125.97 cM with an average distance of 0.31 cM between the adjacent marker loci. It was divided into 6 linkage groups corresponding to the number of spinach chromosomes. Besides, the combination of Bulked Segregation Analysis (BSA) with SLAF-seq technology(super-BSA) was employed to generate the linkage markers with the sex-determining gene. Combined with the high-density genetic map of spinach, the sex-determining gene X/Y was located at the position of the linkage group (LG) 4 (66.98 cM-69.72 cM and 75.48 cM-92.96 cM), which may be the ideal region for the sex-determining gene. A high-density genetic map of spinach based on the SLAF-seq technique was constructed with a backcross (BC 1 ) population (which is the highest density genetic map of spinach reported at present). At the same time, the sex-determining gene X/Y was mapped to LG4 with super-BSA. This map will offer a suitable basis for further study of spinach, such as gene mapping, map-based cloning of Specific genes, quantitative trait locus (QTL) mapping and marker-assisted selection (MAS). It will also provide an efficient reference for studies on the mechanism of sex determination in other dioecious plants.

A second generation genetic linkage map of Japanese flounder (Paralichthys olivaceus)

PubMed Central

2010-01-01

Background Japanese flounder (Paralichthys olivaceus) is one of the most economically important marine species in Northeast Asia. Information on genetic markers associated with quantitative trait loci (QTL) can be used in breeding programs to identify and select individuals carrying desired traits. Commercial production of Japanese flounder could be increased by developing disease-resistant fish and improving commercially important traits. Previous maps have been constructed with AFLP markers and a limited number of microsatellite markers. In this study, improved genetic linkage maps are presented. In contrast with previous studies, these maps were built mainly with a large number of codominant markers so they can potentially be used to analyze different families and populations. Results Sex-specific genetic linkage maps were constructed for the Japanese flounder including a total of 1,375 markers [1,268 microsatellites, 105 single nucleotide polymorphisms (SNPs) and two genes]; 1,167 markers are linked to the male map and 1,067 markers are linked to the female map. The lengths of the male and female maps are 1,147.7 cM and 833.8 cM, respectively. Based on estimations of map lengths, the female and male maps covered 79 and 82% of the genome, respectively. Recombination ratio in the new maps revealed F:M of 1:0.7. All linkage groups in the maps presented large differences in the location of sex-specific recombination hot-spots. Conclusions The improved genetic linkage maps are very useful for QTL analyses and marker-assisted selection (MAS) breeding programs for economically important traits in Japanese flounder. In addition, SNP flanking sequences were blasted against Tetraodon nigroviridis (puffer fish) and Danio rerio (zebrafish), and synteny analysis has been carried out. The ability to detect synteny among species or genera based on homology analysis of SNP flanking sequences may provide opportunities to complement initial QTL experiments with candidate gene approaches from homologous chromosomal locations identified in related model organisms. PMID:20937088

Latitudinal variability of the dynamic linkage between temperature and atmospheric carbon dioxide concentrations - Latitudinal variability

NASA Astrophysics Data System (ADS)

Triacca, Umberto; Di Iorio, Francesca

2018-06-01

In this paper, a novel data-driven approach is used to investigate the presence of spatial differences in the dynamic linkage between temperature and atmospheric carbon dioxide concentrations. This linkage seems to be latitude dependent. The main findings of the study are as follows. In the latitude belts surrounding the equator (0°- 24° N and 0°- 24° S), the link seems very similar. On the opposite, the patterns of the temperature CO2 link in the Arctic is very distant from those concerning the equatorial regions and other latitude bands in the South Hemisphere. This big distance is consistent with the so-called Arctic amplification phenomenon. Further, it is important to underline that this observational data-based analysis provides an independent statistical confirmation of the results from global circulation modelling.

MIDAS: software for analysis and visualisation of interallelic disequilibrium between multiallelic markers

PubMed Central

Gaunt, Tom R; Rodriguez, Santiago; Zapata, Carlos; Day, Ian NM

2006-01-01

Background Various software tools are available for the display of pairwise linkage disequilibrium across multiple single nucleotide polymorphisms. The HapMap project also presents these graphics within their website. However, these approaches are limited in their use of data from multiallelic markers and provide limited information in a graphical form. Results We have developed a software package (MIDAS – Multiallelic Interallelic Disequilibrium Analysis Software) for the estimation and graphical display of interallelic linkage disequilibrium. Linkage disequilibrium is analysed for each allelic combination (of one allele from each of two loci), between all pairwise combinations of any type of multiallelic loci in a contig (or any set) of many loci (including single nucleotide polymorphisms, microsatellites, minisatellites and haplotypes). Data are presented graphically in a novel and informative way, and can also be exported in tabular form for other analyses. This approach facilitates visualisation of patterns of linkage disequilibrium across genomic regions, analysis of the relationships between different alleles of multiallelic markers and inferences about patterns of evolution and selection. Conclusion MIDAS is a linkage disequilibrium analysis program with a comprehensive graphical user interface providing novel views of patterns of linkage disequilibrium between all types of multiallelic and biallelic markers. Availability Available from and PMID:16643648

Autosomal Dominant Nonsyndromic Cleft Lip and Palate: Significant Evidence of Linkage at 18q21.1

PubMed Central

Beiraghi, Soraya ; Nath, Swapan K. ; Gaines, Matthew ; Mandhyan, Desh D. ; Hutchings, David ; Ratnamala, Uppala ; McElreavey, Ken ; Bartoloni, Lucia ; Antonarakis, Gregory S. ; Antonarakis, Stylianos E. ; Radhakrishna, Uppala 

2007-01-01

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital facial defects, with an incidence of 1 in 700–1,000 live births among individuals of European descent. Several linkage and association studies of NSCL/P have suggested numerous candidate genes and genomic regions. A genomewide linkage analysis of a large multigenerational family (UR410) with NSCL/P was performed using a single-nucleotide–polymorphism array. Nonparametric linkage (NPL) analysis provided significant evidence of linkage for marker rs728683 on chromosome 18q21.1 (NPL=43.33 and P=.000061; nonparametric LOD=3.97 and P=.00001). Parametric linkage analysis with a dominant mode of inheritance and reduced penetrance resulted in a maximum LOD score of 3.61 at position 47.4 Mb on chromosome 18q21.1. Haplotype analysis with informative crossovers defined a 5.7-Mb genomic region spanned by proximal marker rs1824683 (42,403,918 bp) and distal marker rs768206 (48,132,862 bp). Thus, a novel genomic region on 18q21.1 was identified that most likely harbors a high-risk variant for NSCL/P in this family; we propose to name this locus “OFC11” (orofacial cleft 11). PMID:17564975

Genetic studies of stuttering in a founder population.

PubMed

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 with nominal evidence for linkage were found on chromosomes 3 (P=0.013, 208.8 centiMorgans (cM)), 13 (P=0.012, 52.6 cM), and 15 (P=0.02, 100 cM). Regions with nominal evidence for association with stuttering that overlapped with a linkage signal are located on chromosomes 3 (P=0.0047, 195 cM), 9 (P=0.0067, 46.5 cM), and 13 (P=0.0055, 52.6 cM). We also conducted the first meta-analysis for stuttering using results from linkage studies in the Hutterites and The Illinois International Genetics of Stuttering Project and identified regions with nominal evidence for linkage on chromosomes 2 (P=0.013, 180-195 cM) and 5 (P=0.0051, 105-120 cM; P=0.015, 120-135 cM). None of the linkage signals detected in the Hutterite sample alone, or in the meta-analysis, meet genome-wide criteria for significance, although some of the stronger signals overlap linkage mapping signals previously reported for other speech and language disorders. After reading this article, the reader will be able to: (1) summarize information about the background of common disorders and methodology of genetic studies; (2) evaluate the role of genetics in stuttering; (3) discuss the value of using founder populations in genetic studies; (4) articulate the importance of combining several studies in a meta-analysis; (5) discuss the overlap of genetic signals identified in stuttering with other speech and language disorders.

Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis.

PubMed

Stambolian, D; Lewis, R A; Buetow, K; Bond, A; Nussbaum, R

1990-07-01

Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome (MIM 302350) is a disease of unknown pathogenesis characterized by congenital cataracts and dental anomalies. We performed linkage analysis in three kindreds with NHS by using six RFLP markers between Xp11.3 and Xp22.3. Close linkage was found between NHS and polymorphic loci DXS43 (theta = 0 with lod score 2.89), DXS41 (theta = 0 with lod score 3.44), and DXS67 (theta = 0 with lod score 2.74), defined by probes pD2, p99-6, and pB24, respectively. Recombinations were found with the marker loci DXS84 (theta = .04 with lod score 4.13), DXS143 (theta = .06 with lod score 3.11) and DXS7 (theta = .09 with lod score 1.68). Multipoint linkage analysis determined the NHS locus to be linked completely to DXS41 (lod score = 7.07). Our linkage results, combined with analysis of Xp interstitial deletions, suggest that the NHS locus is located within or close to the Xp22.1-Xp22.2 region.

Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis.

PubMed Central

Stambolian, D; Lewis, R A; Buetow, K; Bond, A; Nussbaum, R

1990-01-01

Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome (MIM 302350) is a disease of unknown pathogenesis characterized by congenital cataracts and dental anomalies. We performed linkage analysis in three kindreds with NHS by using six RFLP markers between Xp11.3 and Xp22.3. Close linkage was found between NHS and polymorphic loci DXS43 (theta = 0 with lod score 2.89), DXS41 (theta = 0 with lod score 3.44), and DXS67 (theta = 0 with lod score 2.74), defined by probes pD2, p99-6, and pB24, respectively. Recombinations were found with the marker loci DXS84 (theta = .04 with lod score 4.13), DXS143 (theta = .06 with lod score 3.11) and DXS7 (theta = .09 with lod score 1.68). Multipoint linkage analysis determined the NHS locus to be linked completely to DXS41 (lod score = 7.07). Our linkage results, combined with analysis of Xp interstitial deletions, suggest that the NHS locus is located within or close to the Xp22.1-Xp22.2 region. PMID:1971992

Linkage localization of X-linked Charcot-Marie-Tooth disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergoffen, J.; Trofatter, J.; Haines, J.L.

1993-02-01

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived frommore » work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.« less

Cost-effectiveness of community-based strategies to strengthen the continuum of HIV care in rural South Africa: a health economic modelling analysis.

PubMed

Smith, Jennifer A; Sharma, Monisha; Levin, Carol; Baeten, Jared M; van Rooyen, Heidi; Celum, Connie; Hallett, Timothy B; Barnabas, Ruanne V

2015-04-01

Home HIV counselling and testing (HTC) achieves high coverage of testing and linkage to care compared with existing facility-based approaches, particularly among asymptomatic individuals. In a modelling analysis we aimed to assess the effect on population-level health and cost-effectiveness of a community-based package of home HTC in KwaZulu-Natal, South Africa. We parameterised an individual-based model with data from home HTC and linkage field studies that achieved high coverage (91%) and linkage to antiretroviral therapy (80%) in rural KwaZulu-Natal, South Africa. Costs were derived from a linked microcosting study. The model simulated 10,000 individuals over 10 years and incremental cost-effectiveness ratios were calculated for the intervention relative to the existing status quo of facility-based testing, with costs discounted at 3% annually. The model predicted implementation of home HTC in addition to current practice to decrease HIV-associated morbidity by 10–22% and HIV infections by 9–48% with increasing CD4 cell count thresholds for antiretroviral therapy initiation. Incremental programme costs were US$2·7 million to $4·4 million higher in the intervention scenarios than at baseline, and costs increased with higher CD4 cell count thresholds for antiretroviral therapy initiation; antiretroviral therapy accounted for 48–87% of total costs. Incremental cost-effectiveness ratios per disability-adjusted life-year averted were $1340 at an antiretroviral therapy threshold of CD4 count lower than 200 cells per μL, $1090 at lower than 350 cells per μL, $1150 at lower than 500 cells per μL, and $1360 at universal access to antiretroviral therapy. Community-based HTC with enhanced linkage to care can result in increased HIV testing coverage and treatment uptake, decreasing the population burden of HIV-associated morbidity and mortality. The incremental cost-effectiveness ratios are less than 20% of South Africa's gross domestic product per person, and are therefore classed as very cost effective. Home HTC can be a viable means to achieve UNAIDS' ambitious new targets for HIV treatment coverage. National Institutes of Health, Bill & Melinda Gates Foundation, Wellcome Trust.

PRKCA: A Positional Candidate Gene for Body Mass Index and Asthma

PubMed Central

Murphy, Amy; Tantisira, Kelan G.; Soto-Quirós, Manuel E.; Avila, Lydiana; Klanderman, Barbara J.; Lake, Stephen; Weiss, Scott T.; Celedón, Juan C.

2009-01-01

Asthma incidence and prevalence are higher in obese individuals. A potential mechanistic basis for this relationship is pleiotropy. We hypothesized that significant linkage and candidate-gene association would be found for body mass index (BMI) in a population ascertained on asthma affection status. Linkage analysis for BMI was performed on 657 subjects in eight Costa Rican families enrolled in a study of asthma. Family-based association studies were conducted for BMI with SNPs within a positional candidate gene, PRKCA. SNPs within PRKCA were also tested for association with asthma. Association studies were conducted in 415 Costa Rican parent-child trios and 493 trios participating in the Childhood Asthma Management Program (CAMP). Although only modest evidence of linkage for BMI was obtained for the whole cohort, significant linkage was noted for BMI in females on chromosome 17q (peak LOD = 3.39). Four SNPs in a candidate gene in this region (PRKCA) had unadjusted association p values < 0.05 for BMI in both cohorts, with the joint p value for two SNPs remaining significant after adjustment for multiple comparisons (rs228883 and rs1005651, joint p values = 9.5 × 10−5 and 5.6 × 10−5). Similarly, eight SNPs had unadjusted association p values < 0.05 for asthma in both populations, with one SNP remaining significant after adjustment for multiple comparisons (rs11079657, joint p value = 2.6 × 10−5). PRKCA is a pleiotropic locus that is associated with both BMI and asthma and that has been identified via linkage analysis of BMI in a population ascertained on asthma. PMID:19576566

Toward a Molecular Cytogenetic Map for Cultivated Sunflower (Helianthus annuus L.) by Landed BAC/BIBAC Clones

PubMed Central

Feng, Jiuhuan; Liu, Zhao; Cai, Xiwen; Jan, Chao-Chien

2013-01-01

Conventional karyotypes and various genetic linkage maps have been established in sunflower (Helianthus annuus L., 2n = 34). However, the relationship between linkage groups and individual chromosomes of sunflower remains unknown and has considerable relevance for the sunflower research community. Recently, a set of linkage group-specific bacterial /binary bacterial artificial chromosome (BAC/BIBAC) clones was identified from two complementary BAC and BIBAC libraries constructed for cultivated sunflower cv. HA89. In the present study, we used these linkage group-specific clones (∼100 kb in size) as probes to in situ hybridize to HA89 mitotic chromosomes at metaphase using the BAC- fluorescence in situ hybridization (FISH) technique. Because a characteristic of the sunflower genome is the abundance of repetitive DNA sequences, a high ratio of blocking DNA to probe DNA was applied to hybridization reactions to minimize the background noise. As a result, all sunflower chromosomes were anchored by one or two BAC/BIBAC clones with specific FISH signals. FISH analysis based on tandem repetitive sequences, such as rRNA genes, has been previously reported; however, the BAC-FISH technique developed here using restriction fragment length polymorphism (RFLP)−derived BAC/BIBAC clones as probes to apply genome-wide analysis is new for sunflower. As chromosome-specific cytogenetic markers, the selected BAC/BIBAC clones that encompass the 17 linkage groups provide a valuable tool for identifying sunflower cytogenetic stocks (such as trisomics) and tracking alien chromosomes in interspecific crosses. This work also demonstrates the potential of using a large-insert DNA library for the development of molecular cytogenetic resources. PMID:23316437

The Power to Detect Linkage Disequilibrium with Quantitative Traits in Selected Samples

PubMed Central

Abecasis, Gonçalo R.; Cookson, William O. C.; Cardon, Lon R.

2001-01-01

Results from power studies for linkage detection have led to many ongoing and planned collections of phenotypically extreme nuclear families. Given the great expense of collecting these families and the imminent availability of a dense diallelic marker map, the families are likely to be used in allelic-association as well as linkage studies. However, optimal selection strategies for linkage may not be equally powerful for association. We examine the power to detect linkage disequilibrium for quantitative traits after phenotypic selection. The results encompass six selection strategies that are in widespread use, including single selection (two designs), affected sib pairs, concordant and discordant pairs, and the extreme-concordant and -discordant design. Selection of sibships on the basis of one extreme proband with high or low trait scores provides as much power as discordant sib pairs but requires the screening and phenotyping of substantially fewer initial families from which to select. Analysis of the role of allele frequencies within each selection design indicates that common trait alleles generally offer the most power, but similarities between the marker- and trait-allele frequencies are much more important than the trait-locus frequency alone. Some of the most widespread selection designs, such as single selection, yield power gains only when both the marker and quantitative trait loci (QTL) are relatively rare in the population. In contrast, discordant pairs and the extreme-proband design provide power for the broadest range of QTL–marker-allele frequency differences. Overall, proband selection from either tail provides the best balance of power, robustness, and simplicity of ascertainment for family-based association analysis. PMID:11349228

Genome-wide linkage scan for contraction velocity characteristics of knee musculature in the Leuven Genes for Muscular Strength Study.

PubMed

De Mars, Gunther; Windelinckx, An; Huygens, Wim; Peeters, Maarten W; Beunen, Gaston P; Aerssens, Jeroen; Vlietinck, Robert; Thomis, Martine A I

2008-09-17

The torque-velocity relationship is known to be affected by ageing, decreasing its protective role in the prevention of falls. Interindividual variability in this torque-velocity relationship is partly determined by genetic factors (h(2): 44-67%). As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to the torque-velocity relationship of the knee flexors and extensors. A selection of 283 informative male siblings (17-36 yr), belonging to 105 families, was used to conduct a genome-wide SNP-based (Illumina Linkage IVb panel) multipoint linkage analysis for the torque-velocity relationship of the knee flexors and extensors. The strongest evidence for linkage was found at 15q23 for the torque-velocity slope of the knee extensors (TVSE). Other interesting linkage regions with LOD scores >2 were found at 7p12.3 [logarithm of the odds ratio (LOD) = 2.03, P = 0.0011] for the torque-velocity ratio of the knee flexors (TVRF), at 2q14.3 (LOD = 2.25, P = 0.0006) for TVSE, and at 4p14 and 18q23 for the torque-velocity ratio of the knee extensors TVRE (LOD = 2.23 and 2.08; P = 0.0007 and 0.001, respectively). We conclude that many small contributing genes are involved in causing variation in the torque-velocity relationship of the knee flexor and extensor muscles. Several earlier reported candidate genes for muscle strength and muscle mass and new candidates are harbored within or in close vicinity of the linkage regions reported in the present study.

A SNP based high-density linkage map of Apis cerana reveals a high recombination rate similar to Apis mellifera.

PubMed

Shi, Yuan Yuan; Sun, Liang Xian; Huang, Zachary Y; Wu, Xiao Bo; Zhu, Yong Qiang; Zheng, Hua Jun; Zeng, Zhi Jiang

2013-01-01

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. 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. 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.

Distribution and magnitude of type I error of model-based multipoint lod scores: implications for multipoint mod scores.

PubMed

Xing, Chao; Elston, Robert C

2006-07-01

The multipoint lod score and mod score methods have been advocated for their superior power in detecting linkage. However, little has been done to determine the distribution of multipoint lod scores or to examine the properties of mod scores. In this paper we study the distribution of multipoint lod scores both analytically and by simulation. We also study by simulation the distribution of maximum multipoint lod scores when maximized over different penetrance models. The multipoint lod score is approximately normally distributed with mean and variance that depend on marker informativity, marker density, specified genetic model, number of pedigrees, pedigree structure, and pattern of affection status. When the multipoint lod scores are maximized over a set of assumed penetrances models, an excess of false positive indications of linkage appear under dominant analysis models with low penetrances and under recessive analysis models with high penetrances. Therefore, caution should be taken in interpreting results when employing multipoint lod score and mod score approaches, in particular when inferring the level of linkage significance and the mode of inheritance of a trait.

Genetic mapping and QTL analysis of agronomic traits in Indian Mucuna pruriens using an intraspecific F₂population.

PubMed

Mahesh, S; Leelambika, M; Jaheer, Md; Anithakumari, A M; Sathyanarayana, N

2016-03-01

Mucuna pruriens is a well-recognized agricultural and horticultural crop with important medicinal use. However, antinutritional factors in seed and adverse morphological characters have negatively affected its cultivation. To elucidate the genetic control of agronomic traits, an intraspecific genetic linkage map of Indian M. pruriens has been developed based on amplified fragment length polymorphism (AFLP) markers using 200 F₂ progenies derived from a cross between wild and cultivated genotypes. The resulting linkage map comprised 129 AFLP markers dispersed over 13 linkage groups spanning a total distance of 618.88 cM with an average marker interval of 4.79 cM. For the first time, three QTLs explaining about 6.05-14.77% of the corresponding total phenotypic variation for three quantitative (seed) traits and, eight QTLs explaining about 25.96% of the corresponding total phenotypic variation for three qualitative traits have been detected on four linkage groups. The map presented here will pave a way for mapping of genes/QTLs for the important agronomic and horticultural traits contrasting between the parents used in this study.

Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families.

PubMed

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 language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD.

Testing association and linkage using affected-sib-parent study designs.

PubMed

Millstein, Joshua; Siegmund, Kimberly D; Conti, David V; Gauderman, W James

2005-11-01

We have developed a method for jointly testing linkage and association using data from affected sib pairs and their parents. We specify a conditional logistic regression model with two covariates, one that quantifies association (either direct association or indirect association via linkage disequilibrium), and a second that quantifies linkage. The latter covariate is computed based on expected identity-by-descend (ibd) sharing of marker alleles between siblings. In addition to a joint test of linkage and association, our general framework can be used to obtain a linkage test comparable to the mean test (Blackwelder and Elston [1985] Genet. Epidemiol. 2:85-97), and an association test comparable to the Family-Based Association Test (FBAT; Rabinowitz and Laird [2000] Hum. Hered. 50:211-223). We present simulation results demonstrating that our joint test can be more powerful than some standard tests of linkage or association. For example, with a relative risk of 2.7 per variant allele at a disease locus, the estimated power to detect a nearby marker with a modest level of LD was 58.1% by the mean test (linkage only), 69.8% by FBAT, and 82.5% by our joint test of linkage and association. Our model can also be used to obtain tests of linkage conditional on association and association conditional on linkage, which can be helpful in fine mapping. Copyright 2005 Wiley-Liss, Inc.

Analysis of short tandem repeat polymorphisms using infrared fluorescence with M18 tailed primers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oetting, W.S.; Wiesner, G.; Laken, S.

The use of short tandem repeat polymorphisms (STRPs) are becoming increasingly important as markers for linkage analysis due to their large numbers of the human genome and their high degree of polymorphism. Fluorescence based detection of the STRP pattern using the LI-COR model 4000S automated DNA sequencer eliminates the need for radioactivity and produces a digitized image that can be used for the analysis of the polymorphisms. In an effort to reduce the cost of STRP analysis, we have synthesized primers with a 19 bp extension complementary to the sequence of the M13 primer on the 5{prime} end of onemore » of the two primers used in the amplification of the STRP instead of using primers with direct conjugation of the infrared fluorescent dye. Up to 5 primer pairs can be multiplexed together with the M13 primer-dye conjugate as the sole primer conjugated to the fluorescent dye. Comparisons between primers that have been directly conjugated to the fluor with those having the M13 sequence extension show no difference in the ability to determine the STRP pattern. At present, the entire Weber 4A set of STRP markers is available with the M13 5{prime} extension. We are currently using this technique for linkage analysis of familial breast cancer and asthma. The combination of STRP analysis using fluorescence detection will allow this technique to be fully automated for allele scoring and linkage analysis.« less

Construction of the model for the Genetic Analysis Workshop 14 simulated data: genotype-phenotype relationships, gene interaction, linkage, association, disequilibrium, and ascertainment effects for a complex phenotype.

PubMed

Greenberg, David A; Zhang, Junying; Shmulewitz, Dvora; Strug, Lisa J; Zimmerman, Regina; Singh, Veena; Marathe, Sudhir

2005-12-30

The Genetic Analysis Workshop 14 simulated dataset was designed 1) To test the ability to find genes related to a complex disease (such as alcoholism). Such a disease may be given a variety of definitions by different investigators, have associated endophenotypes that are common in the general population, and is likely to be not one disease but a heterogeneous collection of clinically similar, but genetically distinct, entities. 2) To observe the effect on genetic analysis and gene discovery of a complex set of gene x gene interactions. 3) To allow comparison of microsatellite vs. large-scale single-nucleotide polymorphism (SNP) data. 4) To allow testing of association to identify the disease gene and the effect of moderate marker x marker linkage disequilibrium. 5) To observe the effect of different ascertainment/disease definition schemes on the analysis. Data was distributed in two forms. Data distributed to participants contained about 1,000 SNPs and 400 microsatellite markers. Internet-obtainable data consisted of a finer 10,000 SNP map, which also contained data on controls. While disease characteristics and parameters were constant, four "studies" used varying ascertainment schemes based on differing beliefs about disease characteristics. One of the studies contained multiplex two- and three-generation pedigrees with at least four affected members. The simulated disease was a psychiatric condition with many associated behaviors (endophenotypes), almost all of which were genetic in origin. The underlying disease model contained four major genes and two modifier genes. The four major genes interacted with each other to produce three different phenotypes, which were themselves heterogeneous. The population parameters were calibrated so that the major genes could be discovered by linkage analysis in most datasets. The association evidence was more difficult to calibrate but was designed to find statistically significant association in 50% of datasets. We also simulated some marker x marker linkage disequilibrium around some of the genes and also in areas without disease genes. We tried two different methods to simulate the linkage disequilibrium.

Teaching Principles of Linkage and Gene Mapping with the Tomato.

ERIC Educational Resources Information Center

Hawk, James A.; And Others

1980-01-01

A three-point linkage system in tomatoes is used to explain concepts of gene mapping, linking and statistical analysis. The system is designed for teaching the effective use of statistics, and the power of genetic analysis from statistical analysis of phenotypic ratios. (Author/SA)

Linkage analysis by genotyping of sibling populations: a genetic map for the potato cyst nematode constructed using a "pseudo-F2" mapping strategy.

PubMed

Rouppe van der Voort, J N; van Eck, H J; van Zandvoort, P M; Overmars, H; Helder, J; Bakker, J

1999-07-01

A mapping strategy is described for the construction of a linkage map of a non-inbred species in which individual offspring genotypes are not amenable to marker analysis. After one extra generation of random mating, the segregating progeny was propagated, and bulked populations of offspring were analyzed. Although the resulting population structure is different from that of commonly used mapping populations, we show that the maximum likelihood formula for a normal F2 is applicable for the estimation of recombination. This "pseudo-F2" mapping strategy, in combination with the development of an AFLP assay for single cysts, facilitated the construction of a linkage map for the potato cyst nematode Globodera rostochiensis. Using 12 pre-selected AFLP primer combinations, a total of 66 segregating markers were identified, 62 of which were mapped to nine linkage groups. These 62 AFLP markers are randomly distributed and cover about 65% of the genome. An estimate of the physical size of the Globodera genome was obtained from comparisons of the number of AFLP fragments obtained with the values for Caenorhabditis elegans. The methodology presented here resulted in the first genomic map for a cyst nematode. The low value of the kilobase/centimorgan (kb/cM) ratio for the Globodera genome will facilitate map-based cloning of genes that mediate the interaction between the nematode and its host plant.

Linkage Analysis of a Model Quantitative Trait in Humans: Finger Ridge Count Shows Significant Multivariate Linkage to 5q14.1

PubMed Central

Medland, Sarah E; Loesch, Danuta Z; Mdzewski, Bogdan; Zhu, Gu; Montgomery, Grant W; Martin, Nicholas G

2007-01-01

The finger ridge count (a measure of pattern size) is one of the most heritable complex traits studied in humans and has been considered a model human polygenic trait in quantitative genetic analysis. Here, we report the results of the first genome-wide linkage scan for finger ridge count in a sample of 2,114 offspring from 922 nuclear families. Both univariate linkage to the absolute ridge count (a sum of all the ridge counts on all ten fingers), and multivariate linkage analyses of the counts on individual fingers, were conducted. The multivariate analyses yielded significant linkage to 5q14.1 (Logarithm of odds [LOD] = 3.34, pointwise-empirical p-value = 0.00025) that was predominantly driven by linkage to the ring, index, and middle fingers. The strongest univariate linkage was to 1q42.2 (LOD = 2.04, point-wise p-value = 0.002, genome-wide p-value = 0.29). In summary, the combination of univariate and multivariate results was more informative than simple univariate analyses alone. Patterns of quantitative trait loci factor loadings consistent with developmental fields were observed, and the simple pleiotropic model underlying the absolute ridge count was not sufficient to characterize the interrelationships between the ridge counts of individual fingers. PMID:17907812

Linkage Analysis of Quantitative Refraction and Refractive Errors in the Beaver Dam Eye Study

PubMed Central

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

2011-01-01

Purpose. 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. Methods. 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. Results. 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. Conclusions. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11. PMID:21571680

Linkage Determination of Linear Oligosaccharides by MSn (n > 2) Collision-Induced Dissociation of Z1 Ions in the Negative Ion Mode

NASA Astrophysics Data System (ADS)

Konda, Chiharu; Bendiak, Brad; Xia, Yu

2014-02-01

Obtaining unambiguous linkage information between sugars in oligosaccharides is an important step in their detailed structural analysis. An approach is described that provides greater confidence in linkage determination for linear oligosaccharides based on multiple-stage tandem mass spectrometry (MSn, n >2) and collision-induced dissociation (CID) of Z1 ions in the negative ion mode. Under low energy CID conditions, disaccharides 18O-labeled on the reducing carbonyl group gave rise to Z1 product ions (m/z 163) derived from the reducing sugar, which could be mass-discriminated from other possible structural isomers having m/z 161. MS3 CID of these m/z 163 ions showed distinct fragmentation fingerprints corresponding to the linkage types and largely unaffected by sugar unit identities or their anomeric configurations. This unique property allowed standard CID spectra of Z1 ions to be generated from a small set of disaccharide samples that were representative of many other possible isomeric structures. With the use of MSn CID (n = 3 - 5), model linear oligosaccharides were dissociated into overlapping disaccharide structures, which were subsequently fragmented to form their corresponding Z1 ions. CID data of these Z1 ions were collected and compared with the standard database of Z1 ion CID using spectra similarity scores for linkage determination. As the proof-of-principle tests demonstrated, we achieved correct determination of individual linkage types along with their locations within two trisaccharides and a pentasaccharide.

Large displacement behavior of double parallelogram flexure mechanisms with underconstraint eliminators

DOE PAGES

Panas, Robert M.

2016-06-23

This paper presents a new analytical method for predicting the large displacement behavior of flexural double parallelogram (DP) bearings with underconstraint eliminator (UE) linkages. This closed-form perturbative Euler analysis method is able to – for the first time – directly incorporate the elastomechanics of a discrete UE linkage, which is a hybrid flexure element that is linked to ground as well as both stages on the bearing. The models are used to understand a nested linkage UE design, however the method is extensible to other UE linkages. Design rules and figures-of-merit are extracted from the analysis models, which provide powerfulmore » tools for accelerating the design process. The models, rules and figures-of-merit enable the rapid design of a UE for a desired large displacement behavior, as well as providing a means for determining the limits of UE and DP structures. This will aid in the adoption of UE linkages into DP bearings for precision mechanisms. Models are generated for a nested linkage UE design, and the performance of this DP with UE structure is compared to a DP-only bearing. As a result, the perturbative Euler analysis is shown to match existing theories for DP-only bearings with distributed compliance within ≈2%, and Finite Element Analysis for the DP with UE bearings within an average 10%.« less

Large displacement behavior of double parallelogram flexure mechanisms with underconstraint eliminators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panas, Robert M.

This paper presents a new analytical method for predicting the large displacement behavior of flexural double parallelogram (DP) bearings with underconstraint eliminator (UE) linkages. This closed-form perturbative Euler analysis method is able to – for the first time – directly incorporate the elastomechanics of a discrete UE linkage, which is a hybrid flexure element that is linked to ground as well as both stages on the bearing. The models are used to understand a nested linkage UE design, however the method is extensible to other UE linkages. Design rules and figures-of-merit are extracted from the analysis models, which provide powerfulmore » tools for accelerating the design process. The models, rules and figures-of-merit enable the rapid design of a UE for a desired large displacement behavior, as well as providing a means for determining the limits of UE and DP structures. This will aid in the adoption of UE linkages into DP bearings for precision mechanisms. Models are generated for a nested linkage UE design, and the performance of this DP with UE structure is compared to a DP-only bearing. As a result, the perturbative Euler analysis is shown to match existing theories for DP-only bearings with distributed compliance within ≈2%, and Finite Element Analysis for the DP with UE bearings within an average 10%.« less

Search for a schizophrenia susceptibility locus of human chromosome 22

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coon, H.; Hoff, M.; Holik, J.

1994-06-15

We used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib-pair analysis was inconclusive. Affected Pedigree Member (APM) analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non-significant results for the three differentmore » weighting functions. 18 refs., 1 fig., 7 tabs.« less

Extracting topographic structure from digital elevation data for geographic information-system analysis

USGS Publications Warehouse

Jenson, Susan K.; Domingue, Julia O.

1988-01-01

The first phase of analysis is a conditioning phase that generates three data sets: the original OEM with depressions filled, a data set indicating the flow direction for each cell, and a flow accumulation data set in which each cell receives a value equal to the total number of cells that drain to it. The original OEM and these three derivative data sets can then be processed in a variety of ways to optionally delineate drainage networks, overland paths, watersheds for userspecified locations, sub-watersheds for the major tributaries of a drainage network, or pour point linkages between watersheds. The computer-generated drainage lines and watershed polygons and the pour point linkage information can be transferred to vector-based geographic information systems for futher analysis. Comparisons between these computergenerated features and their manually delineated counterparts generally show close agreement, indicating that these software tools will save analyst time spent in manual interpretation and digitizing.

[Analysis on genetic polymorphism of 5 STR loci selected from X chromosome].

PubMed

Liu, Qi-ji; Gong, Yao-qin; Zhang, Xi-yu; Gao, Gui-min; Li, Jiang-xia; Guo, Yi-shou

2005-02-01

To select short tandem repeats(STR) from X chromosome. STR is a universal genetic marker that has changeable polymorphism and stable heredity in human genome. It is a specific DNA segment composed of 2-6 base pairs as its core sequence. It is an ideal DNA marker used in linkage analysis and gene mapping. In this study, 8 short tandem repeats were selected from two genomic clones on X chromosome by using BCM Search Launcher. Primers amplifying the STR loci were designed by using Primer 3.0 according to the unique sequence flanking the STRs. Polymorphisms of the short tandem repeats in Chinese population were evaluated by PCR amplification and PAGE. Five of these STRs were polymorphic. Chi-square test indicated that the distribution of genotypes agreed with Hardy-Weinberg equilibrium (P>0.05). Five polymorphic short tandem repeats have been identified on chromosome X and will be useful for linkage analysis and gene mapping.

Linking Development Benefits to Neighborhoods: A Manual of Community-Based Strategies. Technical Bulletin.

ERIC Educational Resources Information Center

Casale, Ellen

This manual collects experiences of successful linkage programs to demonstrate the promise of linkage and to show its limits and risks. It is intended to help communities assess the capacity of linkage to meet their needs and evaluate the considerable commitment this strategy requires. (In linkage programs, developers who receive community…

Genotyping-by-sequencing enables linkage mapping in three octoploid cultivated strawberry families

PubMed Central

Salinas, Natalia; Tennessen, Jacob A.; Zurn, Jason D.; Sargent, Daniel James; Hancock, James; Bassil, Nahla V.

2017-01-01

Genotyping-by-sequencing (GBS) was used to survey genome-wide single-nucleotide polymorphisms (SNPs) in three biparental strawberry (Fragaria × ananassa) populations with the goal of evaluating this technique in a species with a complex octoploid genome. GBS sequence data were aligned to the F. vesca ‘Fvb’ reference genome in order to call SNPs. Numbers of polymorphic SNPs per population ranged from 1,163 to 3,190. Linkage maps consisting of 30–65 linkage groups were produced from the SNP sets derived from each parent. The linkage groups covered 99% of the Fvb reference genome, with three to seven linkage groups from a given parent aligned to any particular chromosome. A phylogenetic analysis performed using the POLiMAPS pipeline revealed linkage groups that were most similar to ancestral species F. vesca for each chromosome. Linkage groups that were most similar to a second ancestral species, F. iinumae, were only resolved for Fvb 4. The quantity of missing data and heterogeneity in genome coverage inherent in GBS complicated the analysis, but POLiMAPS resolved F. × ananassa chromosomal regions derived from diploid ancestor F. vesca. PMID:28875078

Ignoring Intermarker Linkage Disequilibrium Induces False-Positive Evidence of Linkage for Consanguineous Pedigrees when Genotype Data Is Missing for Any Pedigree Member

PubMed Central

Li, Bingshan; Leal, Suzanne M.

2008-01-01

Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al. [1] that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for autosomal recessive consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. False-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage, and which family members aid in its reduction, is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband's sibling-grandparents. For the situation, when parental genotypes are unavailable, false-positive evidence for linkage can be reduced by including genotype data from either unaffected siblings of the proband or the proband's married-in-grandparents in the analysis. PMID:18073490

The first genetic map of a synthesized allohexaploid Brassica with A, B and C genomes based on simple sequence repeat markers.

PubMed

Yang, S; Chen, S; Geng, X X; Yan, G; Li, Z Y; Meng, J L; Cowling, W A; Zhou, W J

2016-04-01

We present the first genetic map of an allohexaploid Brassica species, based on segregating microsatellite markers in a doubled haploid mapping population generated from a hybrid between two hexaploid parents. This study reports the first genetic map of trigenomic Brassica. A doubled haploid mapping population consisting of 189 lines was obtained via microspore culture from a hybrid H16-1 derived from a cross between two allohexaploid Brassica lines (7H170-1 and Y54-2). Simple sequence repeat primer pairs specific to the A genome (107), B genome (44) and C genome (109) were used to construct a genetic linkage map of the population. Twenty-seven linkage groups were resolved from 274 polymorphic loci on the A genome (109), B genome (49) and C genome (116) covering a total genetic distance of 3178.8 cM with an average distance between markers of 11.60 cM. This is the first genetic framework map for the artificially synthesized Brassica allohexaploids. The linkage groups represent the expected complement of chromosomes in the A, B and C genomes from the original diploid and tetraploid parents. This framework linkage map will be valuable for QTL analysis and future genetic improvement of a new allohexaploid Brassica species, and in improving our understanding of the genetic control of meiosis in new polyploids.

Correlation between quantitative traits and correlation between corresponding LOD scores: detection of pleiotropic effects.

PubMed

Ulgen, Ayse; Han, Zhihua; Li, Wentian

2003-12-31

We address the question of whether statistical correlations among quantitative traits lead to correlation of linkage results of these traits. Five measured quantitative traits (total cholesterol, fasting glucose, HDL cholesterol, blood pressure, and triglycerides), and one derived quantitative trait (total cholesterol divided by the HDL cholesterol) are used for phenotype correlation studies. Four of them are used for linkage analysis. We show that although correlation among phenotypes partially reflects the correlation among linkage analysis results, the LOD-score correlations are on average low. The most significant peaks found by using different traits do not often overlap. Studying covariances at specific locations in LOD scores may provide clues for further bivariate linkage analyses.

Use of linkage mapping and centrality analysis across habitat gradients to conserve connectivity of gray wolf populations in western North America.

PubMed

Carroll, Carlos; McRae, Brad H; Brookes, Allen

2012-02-01

Centrality metrics evaluate paths between all possible pairwise combinations of sites on a landscape to rank the contribution of each site to facilitating ecological flows across the network of sites. Computational advances now allow application of centrality metrics to landscapes represented as continuous gradients of habitat quality. This avoids the binary classification of landscapes into patch and matrix required by patch-based graph analyses of connectivity. It also avoids the focus on delineating paths between individual pairs of core areas characteristic of most corridor- or linkage-mapping methods of connectivity analysis. Conservation of regional habitat connectivity has the potential to facilitate recovery of the gray wolf (Canis lupus), a species currently recolonizing portions of its historic range in the western United States. We applied 3 contrasting linkage-mapping methods (shortest path, current flow, and minimum-cost-maximum-flow) to spatial data representing wolf habitat to analyze connectivity between wolf populations in central Idaho and Yellowstone National Park (Wyoming). We then applied 3 analogous betweenness centrality metrics to analyze connectivity of wolf habitat throughout the northwestern United States and southwestern Canada to determine where it might be possible to facilitate range expansion and interpopulation dispersal. We developed software to facilitate application of centrality metrics. Shortest-path betweenness centrality identified a minimal network of linkages analogous to those identified by least-cost-path corridor mapping. Current flow and minimum-cost-maximum-flow betweenness centrality identified diffuse networks that included alternative linkages, which will allow greater flexibility in planning. Minimum-cost-maximum-flow betweenness centrality, by integrating both land cost and habitat capacity, allows connectivity to be considered within planning processes that seek to maximize species protection at minimum cost. Centrality analysis is relevant to conservation and landscape genetics at a range of spatial extents, but it may be most broadly applicable within single- and multispecies planning efforts to conserve regional habitat connectivity. ©2011 Society for Conservation Biology.

Construction of an ultrahigh-density genetic linkage map for Jatropha curcas L. and identification of QTL for fruit yield.

PubMed

Xia, Zhiqiang; Zhang, Shengkui; Wen, Mingfu; Lu, Cheng; Sun, Yufang; Zou, Meiling; Wang, Wenquan

2018-01-01

As an important biofuel plant, the demand for higher yield Jatropha curcas L. is rapidly increasing. However, genetic analysis of Jatropha and molecular breeding for higher yield have been hampered by the limited number of molecular markers available. An ultrahigh-density linkage map for a Jatropha mapping population of 153 individuals was constructed and covered 1380.58 cM of the Jatropha genome, with average marker density of 0.403 cM. The genetic linkage map consisted of 3422 SNP and indel markers, which clustered into 11 linkage groups. With this map, 13 repeatable QTLs (reQTLs) for fruit yield traits were identified. Ten reQTLs, qNF - 1 , qNF - 2a , qNF - 2b , qNF - 2c , qNF - 3 , qNF - 4 , qNF - 6 , qNF - 7a , qNF - 7b and qNF - 8, that control the number of fruits (NF) mapped to LGs 1, 2, 3, 4, 6, 7 and 8, whereas three reQTLs, qTWF - 1 , qTWF - 2 and qTWF - 3, that control the total weight of fruits (TWF) mapped to LGs 1, 2 and 3, respectively. It is interesting that there are two candidate critical genes, which may regulate Jatropha fruit yield. We also identified three pleiotropic reQTL pairs associated with both the NF and TWF traits. This study is the first to report an ultrahigh-density Jatropha genetic linkage map construction, and the markers used in this study showed great potential for QTL mapping. Thirteen fruit-yield reQTLs and two important candidate genes were identified based on this linkage map. This genetic linkage map will be a useful tool for the localization of other economically important QTLs and candidate genes for Jatropha .

Linkage studies in primary open angle glaucoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avramopoulos, D.; Grigoriadu, M.; Kitsos, G.

1994-09-01

Glaucoma is a leading cause of blindness worldwide. The majority of glaucoma is associated with an open, normal appearing anterior chamber angle and is termed primary open angle glaucoma (POAG, MIM 137760). It is characterized by elevated intraocular pressure and onset in middle age or later. A subset of POAG with juvenile onset has recently been linked to chromosome 1q in two families with autosomal dominant inheritance. Eleven pedigrees with autosomal dominant POG (non-juvenile-onset) have been identified in Epirus, Greece. In the present study DNA samples have been collected from 50 individuals from one large pedigree, including 12 affected individuals.more » Preliminary results of linkage analysis with chromosome 1 microsatellites using the computer program package LINKAGE Version 5.1 showed no linkage with the markers previously linked to juvenile-onset POAG. Further linkage analysis is being pursued, and the results will be presented.« less

No evidence for linkage between the X-chromosome marker DXS7 and schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okoro, C.; Bell, R.; Sham, P.

DeLisi et al. have examined the X and Y chromosomes for linkage to schizophrenia in 126 small families and report a small positive LOD score for the marker DXS7, adjacent to the MAO locus at Xp11.4-11.3. Because of this, we have examined the DXS7 for linkage to schizophrenia using 17 pedigrees in which male-to-male transmission of schizophrenia was absent. Alleles at DXS7 were genotyped using the PCR and LOD scores calculated using five models of inheritance, including classical dominant, recessive and intermediate models. LOD scores were substantially negative for all models examined and analysis for linkage heterogeneity using the LOD2more » method showed no significance. Analysis by the nonparametric affected sib-pair method likewise indicated no linkage. We conclude that DXS7 is not a major locus for schizophrenia in our collection of pedigrees. 29 refs., 1 tab.« less

Allelic association but only weak evidence for linkage to the apolipoprotein E locus in late-onset Swedish Alzheimer families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, L.; Forsell, C.; Lilius, L.

1996-05-31

An association between the {epsilon}4 allele of the apolipoprotein E gene (APOE) and late-onset Alzheimer`s disease (AD) was recently demonstrated. In order to confirm the association and to gauge the ability of standard genetic linkage methods to identify susceptibility genes, we investigated 15 Swedish late-onset AD families. We found an association of familial AD to the APOE {epsilon}4 allele (P = 0.01) but no indication of linkage to the APOE region using 2-point linkage analysis, and only weak evidence using the affected pedigree-member (APM) method. Our results confirm an APOE {epsilon}4 association with late-onset familial AD and indicate that susceptibilitymore » genes can easily be missed when using standard lod score and APM genetic linkage analysis. 19 refs., 1 fig., 4 tabs.« less

Linking Stream Dissolved Oxygen with the Dynamic Environmental Drivers across the Pacific Coast of U.S.A.

NASA Astrophysics Data System (ADS)

Araya, F. Z.; Abdul-Aziz, O. I.

2017-12-01

This study utilized a systematic data analytics approach to determine the relative linkages of stream dissolved oxygen (DO) with the hydro-climatic and biogeochemical drivers across the U.S. Pacific Coast. Multivariate statistical techniques of Pearson correlation matrix, principal component analysis, and factor analysis were applied to a complex water quality dataset (1998-2015) at 35 water quality monitoring stations of USGS NWIS and EPA STORET. Power-law based partial least squares regression (PLSR) models with a bootstrap Monte Carlo procedure (1000 iterations) were developed to reliably estimate the relative linkages by resolving multicollinearity (Nash-Sutcliffe Efficiency, NSE = 0.50-0.94). Based on the dominant drivers, four environmental regimes have been identified and adequately described the system-data variances. In Pacific North West and Southern California, water temperature was the most dominant driver of DO in majority of the streams. However, in Central and Northern California, stream DO was controlled by multiple drivers (i.e., water temperature, pH, stream flow, and total phosphorus), exhibiting a transitional environmental regime. Further, total phosphorus (TP) appeared to be the limiting nutrient for most streams. The estimated linkages and insights would be useful to identify management priorities to achieve healthy coastal stream ecosystems across the Pacific Coast of U.S.A. and similar regions around the world. Keywords: Data analytics, water quality, coastal streams, dissolved oxygen, environmental regimes, Pacific Coast, United States.

Nonlinear Analysis of Time Series in Genome-Wide Linkage Disequilibrium Data

NASA Astrophysics Data System (ADS)

Hernández-Lemus, Enrique; Estrada-Gil, Jesús K.; Silva-Zolezzi, Irma; Fernández-López, J. Carlos; Hidalgo-Miranda, Alfredo; Jiménez-Sánchez, Gerardo

2008-02-01

The statistical study of large scale genomic data has turned out to be a very important tool in population genetics. Quantitative methods are essential to understand and implement association studies in the biomedical and health sciences. Nevertheless, the characterization of recently admixed populations has been an elusive problem due to the presence of a number of complex phenomena. For example, linkage disequilibrium structures are thought to be more complex than their non-recently admixed population counterparts, presenting the so-called ancestry blocks, admixed regions that are not yet smoothed by the effect of genetic recombination. In order to distinguish characteristic features for various populations we have implemented several methods, some of them borrowed or adapted from the analysis of nonlinear time series in statistical physics and quantitative physiology. We calculate the main fractal dimensions (Kolmogorov's capacity, information dimension and correlation dimension, usually named, D0, D1 and D2). We also have made detrended fluctuation analysis and information based similarity index calculations for the probability distribution of correlations of linkage disequilibrium coefficient of six recently admixed (mestizo) populations within the Mexican Genome Diversity Project [1] and for the non-recently admixed populations in the International HapMap Project [2]. Nonlinear correlations showed up as a consequence of internal structure within the haplotype distributions. The analysis of these correlations as well as the scope and limitations of these procedures within the biomedical sciences are discussed.

A population 'consensus', partial linkage map of Picea abies Karst. based on RAPD markers

Treesearch

G. Bucci; Thomas L. Kubisiak; W.L. Nance; P. Menozzi

1997-01-01

The authors built a "consensus" partial linkage map based on RAPD markers using 48 sibships of eight megagametophytes each from a natural population of Norway spruce. A RAPD linkage map for a single individual from the same population had previously been constructed. Using 30 random decamers that had yielded 83 RAPD markers in the single-tree map, eight...

Stratified Whole Genome Linkage Analysis of Chiari Type I Malformation Implicates Known Klippel-Feil Syndrome Genes as Putative Disease Candidates

PubMed Central

Markunas, Christina A.; Soldano, Karen; Dunlap, Kaitlyn; Cope, Heidi; Asiimwe, Edgar; Stajich, Jeffrey; Enterline, David; Grant, Gerald; Fuchs, Herbert

2013-01-01

Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of “CTD-negative” families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3–5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI. PMID:23620759

Refining genome-wide linkage intervals using a meta-analysis of genome-wide association studies identifies loci influencing personality dimensions

PubMed Central

Amin, Najaf; Hottenga, Jouke-Jan; Hansell, Narelle K; Janssens, A Cecile JW; de Moor, Marleen HM; Madden, Pamela AF; Zorkoltseva, Irina V; Penninx, Brenda W; Terracciano, Antonio; Uda, Manuela; Tanaka, Toshiko; Esko, Tonu; Realo, Anu; Ferrucci, Luigi; Luciano, Michelle; Davies, Gail; Metspalu, Andres; Abecasis, Goncalo R; Deary, Ian J; Raikkonen, Katri; Bierut, Laura J; Costa, Paul T; Saviouk, Viatcheslav; Zhu, Gu; Kirichenko, Anatoly V; Isaacs, Aaron; Aulchenko, Yurii S; Willemsen, Gonneke; Heath, Andrew C; Pergadia, Michele L; Medland, Sarah E; Axenovich, Tatiana I; de Geus, Eco; Montgomery, Grant W; Wright, Margaret J; Oostra, Ben A; Martin, Nicholas G; Boomsma, Dorret I; van Duijn, Cornelia M

2013-01-01

Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N∼17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 × 10−06, KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene. PMID:23211697

[The Willingness to Consent to the Linkage of Primary and Secondary Data: An Analysis Based on a Survey of Patients with Primary Breast Cancer in Northrhine Westfalia].

PubMed

Scholten, N; Pfaff, H; Raabe, N; Kowalski, C

2017-03-01

Introduction: By linking data it is possible to merge, for example, survey data with routine data from statutory health insurance (GKV), to gain benefit from the advantages of both. As personal data is involved, it is necessary to obtain consent. Previous studies show that willingness to release this kind of data for scientific research is limited. This fact restricts the number of participants and can cause selection bias. The aim of our study was to analyze willingness to consent to the linkage of survey data with statutory health insurance data in patients with primary breast cancer. Associations between approval and socio-demographic characteristics were explored. Method: In the annual survey of patients with primary breast cancer in certified breast centers in North Rhine-Westphalia, all included patients were questioned concerning their willingness to consent to data linkage. We distinguished between patients insured by AOK Rhineland/Hamburg and all other patients: based on cooperation with AOK Rhineland/Hamburg, we obtained consent to actually link the data for all patients insured there. All other patients were questioned in terms of their insurance and their willingness to consent in general. Results: A total of 2,387 questionnaires were returned, giving a return rate of 49.3%. For the AOK Rhineland/Hamburg-insured patients, the consent rate was at 89.6%. At 75.7%, positive attitudes towards data linkage turned out to be a bit lower for patients with other insurers. Under the assumption that all non-responders disapprove data linkage, still 38.1% of patients showed a positive attitude towards data linkage. As a result of the multivariable model, insurance status (private vs. statutory) and first language turned out to be the only significant factors influencing the response. The consent of patients insured by AOK Rhineland/Hamburg is not significantly influenced by any of the measured socio-demographic factors. Conclusion: Currently, there is not much knowledge on the acceptance of data linkage in patients suffering from an acute illness. Although our results are restricted to breast cancer patients, they are able to uncover problems and chances concerning data linkage. © Georg Thieme Verlag KG Stuttgart · New York.

Genome-wide linkage meta-analysis identifies susceptibility loci at 2q34 and 13q31.3 for genetic generalized epilepsies.

PubMed

Leu, Costin; de Kovel, Carolien G F; Zara, Federico; Striano, Pasquale; Pezzella, Marianna; Robbiano, Angela; Bianchi, Amedeo; Bisulli, Francesca; Coppola, Antonietta; Giallonardo, Anna Teresa; Beccaria, Francesca; Trenité, Dorothée Kasteleijn-Nolst; Lindhout, Dick; Gaus, Verena; Schmitz, Bettina; Janz, Dieter; Weber, Yvonne G; Becker, Felicitas; Lerche, Holger; Kleefuss-Lie, Ailing A; Hallman, Kerstin; Kunz, Wolfram S; Elger, Christian E; Muhle, Hiltrud; Stephani, Ulrich; Møller, Rikke S; Hjalgrim, Helle; Mullen, Saul; Scheffer, Ingrid E; Berkovic, Samuel F; Everett, Kate V; Gardiner, Mark R; Marini, Carla; Guerrini, Renzo; Lehesjoki, Anna-Elina; Siren, Auli; Nabbout, Rima; Baulac, Stephanie; Leguern, Eric; Serratosa, Jose M; Rosenow, Felix; Feucht, Martha; Unterberger, Iris; Covanis, Athanasios; Suls, Arvid; Weckhuysen, Sarah; Kaneva, Radka; Caglayan, Hande; Turkdogan, Dilsad; Baykan, Betul; Bebek, Nerses; Ozbek, Ugur; Hempelmann, Anne; Schulz, Herbert; Rüschendorf, Franz; Trucks, Holger; Nürnberg, Peter; Avanzini, Giuliano; Koeleman, Bobby P C; Sander, Thomas

2012-02-01

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) susceptibility loci shared by a broad spectrum of GGEs, and (2) seizure type-related genetic factors preferentially predisposing to either typical absence or myoclonic seizures, respectively. Meta-analysis of three genome-wide linkage datasets was carried out in 379 GGE-multiplex families of European 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 and seizure type-related susceptibility loci, both nonparametric loci (NPL) and parametric linkage analyses were performed for a broad trait model (GGEs) in the entire set of GGE-multiplex families and a narrow trait model (typical absence or myoclonic seizures) in the subgroups of JME and GAE families. 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 three family groups. A genome-wide significant nonparametric logarithm of odds score of 3.43 was obtained at 2q34 in 118 JME families. Significant parametric linkage to 13q31.3 was found in 235 GAE families assuming recessive inheritance (heterogeneity logarithm of odds = 5.02). Our linkage results support an oligogenic predisposition of familial GGE syndromes. The genetic risk factor at 5q34 confers risk to a broad spectrum of familial GGE syndromes, whereas susceptibility loci at 2q34 and 13q31.3 preferentially predispose to myoclonic seizures or absence seizures, respectively. Phenotype- genotype strategies applying narrow trait definitions in phenotypic homogeneous subgroups of families improve the prospects of disentangling the genetic basis of common familial GGE syndromes. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

A Simple Sequence Repeat- and Single-Nucleotide Polymorphism-Based Genetic Linkage Map of the Brown Planthopper, Nilaparvata lugens

PubMed Central

Jairin, Jirapong; Kobayashi, Tetsuya; Yamagata, Yoshiyuki; Sanada-Morimura, Sachiyo; Mori, Kazuki; Tashiro, Kosuke; Kuhara, Satoru; Kuwazaki, Seigo; Urio, Masahiro; Suetsugu, Yoshitaka; Yamamoto, Kimiko; Matsumura, Masaya; Yasui, Hideshi

2013-01-01

In this study, we developed the first genetic linkage map for the major rice insect pest, the brown planthopper (BPH, Nilaparvata lugens). The linkage map was constructed by integrating linkage data from two backcross populations derived from three inbred BPH strains. The consensus map consists of 474 simple sequence repeats, 43 single-nucleotide polymorphisms, and 1 sequence-tagged site, for a total of 518 markers at 472 unique positions in 17 linkage groups. The linkage groups cover 1093.9 cM, with an average distance of 2.3 cM between loci. The average number of marker loci per linkage group was 27.8. The sex-linkage group was identified by exploiting X-linked and Y-specific markers. Our linkage map and the newly developed markers used to create it constitute an essential resource and a useful framework for future genetic analyses in BPH. PMID:23204257

Individuals and populations: the role of long-term, individual-based studies of animals in ecology and evolutionary biology.

PubMed

Clutton-Brock, Tim; Sheldon, Ben C

2010-10-01

Many important questions in ecology and evolutionary biology can only be answered with data that extend over several decades and answering a substantial proportion of questions requires records of the life histories of recognisable individuals. We identify six advantages that long-term, individual based studies afford in ecology and evolution: (i) analysis of age structure; (ii) linkage between life history stages; (iii) quantification of social structure; (iv) derivation of lifetime fitness measures; (v) replication of estimates of selection; (vi) linkage between generations, and we review their impact on studies in six key areas of evolution and ecology. Our review emphasises the unusual opportunities and productivity of long-term, individual-based studies and documents the important role that they play in research on ecology and evolutionary biology as well as the difficulties they face. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

PubMed

de Miguel, Marina; de Maria, Nuria; Guevara, M Angeles; Diaz, Luis; Sáez-Laguna, Enrique; Sánchez-Gómez, David; Chancerel, Emilie; Aranda, Ismael; Collada, Carmen; Plomion, Christophe; Cabezas, José-Antonio; Cervera, María-Teresa

2012-10-04

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. 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. 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.

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

PubMed Central

2012-01-01

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. PMID:23036012

Genetic linkage map construction and QTL mapping of seedling height, basal diameter and crown width of Taxodium 'Zhongshanshan 302' × T. mucronatum.

PubMed

Wang, Ziyang; Cheng, Yanli; Yin, Yunlong; Yu, Chaoguang; Yang, Ying; Shi, Qin; Hao, Ziyuan; Li, Huogen

2016-01-01

Taxodium is a genus renowned for its fast growth, good form and tolerance of flooding, salt, alkalinity, disease and strong winds. In this study, a genetic linkage map was constructed using sequence-related amplified polymorphism (SRAP) and simple sequence repeat (SSR) markers based on an F1 population containing 148 individuals generated from a cross between T. 'Zhongshanshan 302' and T. mucronatum. The map has a total length of 976.5 cM, with a mean distance of 7.0 cM between markers, and contains 34 linkage groups with 179 markers (171 SRAPs and 8 SSRs). Quantitative trait loci (QTLs) affecting growth traits, such as seedling height, basal diameter and crown width, were detected based on the constructed linkage map. Four significant QTLs were identified, three of which, namely qtSH-1 for seedling height, qtBD-1 for basal diameter and qtCW-1 for crown width, were located at 2.659 cM of LG7 with logarithm odds values of 3.72, 3.49 and 3.93, respectively, and explained 24.9, 27.0 and 21.7 % of the total variation of the three grown traits, respectively. Another QTL for crown width (qtCW-2) was detected at 1.0 cM on LG13, with a logarithm of odds value of 3.15, and explained 31.7 % of the total variation of crown width. This is the first report on the construction of a genetic linkage map and QTL analysis in Taxodium, laying the groundwork for the construction of a high-density genetic map and QTL mapping in the genus Taxodium.

Construction of a microsatellites-based linkage map for the white grouper (Epinephelus aeneus).

PubMed

Dor, Lior; Shirak, Andrey; Gorshkov, Sergei; Band, Mark R; Korol, Abraham; Ronin, Yefim; Curzon, Arie; Hulata, Gideon; Seroussi, Eyal; Ron, Micha

2014-06-05

The white grouper (Epinephelus aeneus) is a promising candidate for domestication and aquaculture due to its fast growth, excellent taste, and high market price. A linkage map is an essential framework for mapping quantitative trait loci for economic traits and the study of genome evolution. DNA of a single individual was deep-sequenced, and microsatellite markers were identified in 177 of the largest scaffolds of the sequence assembly. The success rate of developing polymorphic homologous markers was 94.9% compared with 63.1% of heterologous markers from other grouper species. Of the 12 adult mature fish present in the broodstock tank, two males and two females were identified as parents of the assigned offspring by parenthood analysis using 34 heterologous markers. A single full-sib family of 48 individuals was established for the construction of first-generation linkage maps based on genotyping data of 222 microsatellites. The markers were assigned to 24 linkage groups in accordance to the 24 chromosomal pairs. The female and male maps consisting of 203 and 202 markers spanned 1053 and 886 cM, with an average intermarker distance of 5.8 and 5.0 cM, respectively. Mapping of markers to linkage groups ends was enriched by using markers originating from scaffolds harboring telomeric repeat-containing RNA. Comparative mapping showed high synteny relationships among the white grouper, kelp grouper (E. bruneus), orange-spotted grouper (E. coioides), and Nile tilapia (Oreochromis niloticus). Thus, it would be useful to integrate the markers that were developed for different groupers, depending on sharing of sequence data, into a comprehensive consensus map. Copyright © 2014 Dor et al.

Use of linkage disequilibrium approaches to map genes for bipolar disorder in the Costa Rican population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escamilla, M.A.; Reus, V.I.; Smith, L.B.

1996-05-31

Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, should be suitable for LD mapping; this assertion is supported by reconstruction of extended haplotypes shared by distantly related individuals in this population suffering low-frequency hearing loss (LFHL1), which has previously been mapped by linkage analysis. A sampling strategy is described for applying LD methods to map genes for BP, andmore » clinical and demographic characteristics of an initially collected sample are discussed. This sample will provide a complement to a previously collected set of Costa Rican BP families which is under investigation using standard linkage analysis. 42 refs., 4 figs., 2 tabs.« less

A Novel Multiobjective Evolutionary Algorithm Based on Regression Analysis

PubMed Central

Song, Zhiming; Wang, Maocai; Dai, Guangming; Vasile, Massimiliano

2015-01-01

As is known, the Pareto set of a continuous multiobjective optimization problem with m objective functions is a piecewise continuous (m − 1)-dimensional manifold in the decision space under some mild conditions. However, how to utilize the regularity to design multiobjective optimization algorithms has become the research focus. In this paper, based on this regularity, a model-based multiobjective evolutionary algorithm with regression analysis (MMEA-RA) is put forward to solve continuous multiobjective optimization problems with variable linkages. In the algorithm, the optimization problem is modelled as a promising area in the decision space by a probability distribution, and the centroid of the probability distribution is (m − 1)-dimensional piecewise continuous manifold. The least squares method is used to construct such a model. A selection strategy based on the nondominated sorting is used to choose the individuals to the next generation. The new algorithm is tested and compared with NSGA-II and RM-MEDA. The result shows that MMEA-RA outperforms RM-MEDA and NSGA-II on the test instances with variable linkages. At the same time, MMEA-RA has higher efficiency than the other two algorithms. A few shortcomings of MMEA-RA have also been identified and discussed in this paper. PMID:25874246

Advanced Exposure Metrics For Chemical Risk Analysis: Systems Biology and 'Omic-based Biomarkers for Exposure Reconstruction

EPA Science Inventory

Direct measurement of human exposure to environmental contaminants in real time (when the exposure is actually occurring) is rare and difficult to obtain. This frustrates both exposure assessments and investigations into the linkage between chemical exposure and human disease. ...

The ties that bind: interorganizational linkages and physician-system alignment.

PubMed

Alexander, J A; Waters, T M; Burns, L R; Shortell, S M; Gillies, R R; Budetti, P P; Zuckerman, H S

2001-07-01

To examine the association between the degree of alignment between physicians and health care systems, and interorganizational linkages between physician groups and health care systems. The study used a cross sectional, comparative analysis using a sample of 1,279 physicians practicing in loosely affiliated arrangements and 1,781 physicians in 61 groups closely affiliated with 14 vertically integrated health systems. Measures of physician alignment were based on multiitem scales validated in previous studies and derived from surveys sent to individual physicians. Measures of interorganizational linkages were specified at the institutional, administrative, and technical core levels of the physician group and were developed from surveys sent to the administrator of each of the 61 physician groups in the sample. Two stage Heckman models with fixed effects adjustments in the second stage were used to correct for sample selection and clustering respectively. After accounting for sample selection, fixed effects, and group and individual controls, physicians in groups with more valued practice service linkages display consistently higher alignment with systems than physicians in groups that have fewer such linkages. Results also suggest that centralized administrative control lowers physician-system alignment for selected measures of alignment. Governance interlocks exhibited only weak associations with alignment. Our findings suggest that alignment generally follows resource exchanges that promote value-added contributions to physicians and physician groups while preserving control and authority within the group.

Predator community structure and trophic linkage strength to a focal prey.

PubMed

Lundgren, Jonathan G; Fergen, Janet K

2014-08-01

Predator abundance and community structure can affect the suppression of lower trophic levels, although studies of these interactions under field conditions are relatively few. We investigated how the frequency of consumption (measured using PCR-based gut content analysis) is affected by predator abundance, community diversity and evenness under realistic conditions. Soil arthropod communities in sixteen maize fields were measured (number of predators, diversity [Shannon H] and evenness [J]), and predator guts were searched for DNA of the focal subterranean herbivore, the corn rootworm (Diabrotica virgifera). Predator abundance and diversity were positively correlated with trophic linkage strength (the proportion positive for rootworm DNA), although the latter characteristic was not significantly so. The diversity and evenness of the predator community with chewing mouthparts were strongly correlated with their linkage strength to rootworms, whereas the linkage strength of fluid-feeding predators was unaffected by their community characteristics. Within this community, chewing predators are more affected by the rootworm's hemolymph defence. This research clearly shows that predator abundance and diversity influence the strength of a community's trophic linkage to a focal pest and that these community characteristics may be particularly important for less palatable or protected prey species. We also make the case for conserving diverse and abundant predator communities within agroecosystems as a form of pest management. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

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

PubMed

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.

A Simple Sampling Method for Estimating the Accuracy of Large Scale Record Linkage Projects.

PubMed

Boyd, James H; Guiver, Tenniel; Randall, Sean M; Ferrante, Anna M; Semmens, James B; Anderson, Phil; Dickinson, Teresa

2016-05-17

Record linkage techniques allow different data collections to be brought together to provide a wider picture of the health status of individuals. Ensuring high linkage quality is important to guarantee the quality and integrity of research. Current methods for measuring linkage quality typically focus on precision (the proportion of incorrect links), given the difficulty of measuring the proportion of false negatives. The aim of this work is to introduce and evaluate a sampling based method to estimate both precision and recall following record linkage. In the sampling based method, record-pairs from each threshold (including those below the identified cut-off for acceptance) are sampled and clerically reviewed. These results are then applied to the entire set of record-pairs, providing estimates of false positives and false negatives. This method was evaluated on a synthetically generated dataset, where the true match status (which records belonged to the same person) was known. The sampled estimates of linkage quality were relatively close to actual linkage quality metrics calculated for the whole synthetic dataset. The precision and recall measures for seven reviewers were very consistent with little variation in the clerical assessment results (overall agreement using the Fleiss Kappa statistics was 0.601). This method presents as a possible means of accurately estimating matching quality and refining linkages in population level linkage studies. The sampling approach is especially important for large project linkages where the number of record pairs produced may be very large often running into millions.

Evaluating the Use of Existing Data Sources, Probabilistic Linkage, and Multiple Imputation to Build Population-based Injury Databases Across Phases of Trauma Care

PubMed Central

Newgard, Craig; Malveau, Susan; Staudenmayer, Kristan; Wang, N. Ewen; Hsia, Renee Y.; Mann, N. Clay; Holmes, James F.; Kuppermann, Nathan; Haukoos, Jason S.; Bulger, Eileen M.; Dai, Mengtao; Cook, Lawrence J.

2012-01-01

Objectives The objective was to evaluate the process of using existing data sources, probabilistic linkage, and multiple imputation to create large population-based injury databases matched to outcomes. Methods This was a retrospective cohort study of injured children and adults transported by 94 emergency medical systems (EMS) agencies to 122 hospitals in seven regions of the western United States over a 36-month period (2006 to 2008). All injured patients evaluated by EMS personnel within specific geographic catchment areas were included, regardless of field disposition or outcome. The authors performed probabilistic linkage of EMS records to four hospital and postdischarge data sources (emergency department [ED] data, patient discharge data, trauma registries, and vital statistics files) and then handled missing values using multiple imputation. The authors compare and evaluate matched records, match rates (proportion of matches among eligible patients), and injury outcomes within and across sites. Results There were 381,719 injured patients evaluated by EMS personnel in the seven regions. Among transported patients, match rates ranged from 14.9% to 87.5% and were directly affected by the availability of hospital data sources and proportion of missing values for key linkage variables. For vital statistics records (1-year mortality), estimated match rates ranged from 88.0% to 98.7%. Use of multiple imputation (compared to complete case analysis) reduced bias for injury outcomes, although sample size, percentage missing, type of variable, and combined-site versus single-site imputation models all affected the resulting estimates and variance. Conclusions This project demonstrates the feasibility and describes the process of constructing population-based injury databases across multiple phases of care using existing data sources and commonly available analytic methods. Attention to key linkage variables and decisions for handling missing values can be used to increase match rates between data sources, minimize bias, and preserve sampling design. PMID:22506952

Construction of an SSR and RAD-Marker Based Molecular Linkage Map of Vigna vexillata (L.) A. Rich

PubMed Central

Chankaew, Sompong; Kaga, Akito; Naito, Ken; Ehara, Hiroshi; Tomooka, Norihiko

2015-01-01

Vigna vexillata (L.) A. Rich. (tuber cowpea) is an underutilized crop for consuming its tuber and mature seeds. Wild form of V. vexillata is a pan-tropical perennial herbaceous plant which has been used by local people as a food. Wild V. vexillata has also been considered as useful gene(s) source for V. unguiculata (cowpea), since it was reported to have various resistance gene(s) for insects and diseases of cowpea. To exploit the potential of V. vexillata, an SSR-based linkage map of V. vexillata was developed. A total of 874 SSR markers successfully amplified single DNA fragment in V. vexillata among 1,336 SSR markers developed from Vigna angularis (azuki bean), V. unguiculata and Phaseolus vulgaris (common bean). An F2 population of 300 plants derived from a cross between salt resistant (V1) and susceptible (V5) accessions was used for mapping. A genetic linkage map was constructed using 82 polymorphic SSR markers loci, which could be assigned to 11 linkage groups spanning 511.5 cM in length with a mean distance of 7.2 cM between adjacent markers. To develop higher density molecular linkage map and to confirm SSR markers position in a linkage map, RAD markers were developed and a combined SSR and RAD markers linkage map of V. vexillata was constructed. A total of 559 (84 SSR and 475 RAD) markers loci could be assigned to 11 linkage groups spanning 973.9 cM in length with a mean distance of 1.8 cM between adjacent markers. Linkage and genetic position of all SSR markers in an SSR linkage map were confirmed. When an SSR genetic linkage map of V. vexillata was compared with those of V. radiata and V. unguiculata, it was suggested that the structure of V. vexillata chromosome was considerably differentiated. This map is the first SSR and RAD marker-based V. vexillata linkage map which can be used for the mapping of useful traits. PMID:26398819

Technology use in linking criminal justice reentrants to HIV care in the community: a qualitative formative research study.

PubMed

Peterson, James; Cota, Michelle; Gray, Holly; Bazerman, Lauri; Kuo, Irene; Kurth, Ann; Beckwith, Curt

2015-01-01

Innovative interventions increasing linkage, adherence, and retention in care among HIV-infected persons in the criminal justice system are needed. The authors conducted a qualitative study to investigate technology-based tools to facilitate linkage to community-based care and viral suppression for HIV-infected jail detainees on antiretroviral medications being released to the community. The authors conducted 24 qualitative interview-12 in Rhode Island and 12 in Washington, DC-among recently incarcerated HIV-infected persons to elicit their perceptions on the use of technology tools to support linkage to HIV care among criminal justice populations. This article discusses participants' perceptions of the acceptability of technological tools such as (a) a computer-based counseling and (b) text messaging interventions. The participants reported positive experiences when previewing the technology-based tools to facilitate linkage to HIV care and adherence to HIV medications. Successful linkage to care has been shown to improve HIV-associated and non-HIV-associated health outcomes, as well as prevent criminal recidivism and facilitate reentrants' successful and meaningful transition. These findings can be used to inform the implementation of interventions aimed at promoting adherence to antiretroviral medications and linkage to care for HIV-infected persons being released from the correctional setting.

African American church-based HIV testing and linkage to care: assets, challenges and needs.

PubMed

Stewart, Jennifer M; Thompson, Keitra; Rogers, Christopher

2016-01-01

The US National HIV AIDS strategy promotes the use of faith communities to lessen the burden of HIV in African American communities. One specific strategy presented is the use of these non-traditional venues for HIV testing and co-location of services. African American churches can be at the forefront of this endeavour through the provision of HIV testing and linkage to care. However, there are few interventions to promote the churches' involvement in both HIV testing and linkage to care. We conducted 4 focus groups (n = 39 participants), 4 interviews and 116 surveys in a mixed-methods study to examine the feasibility of a church-based HIV testing and linkage to care intervention in Philadelphia, PA, USA. Our objectives were to examine: (1) available assets, (2) challenges and barriers and (3) needs associated with church-based HIV testing and linkage to care. Analyses revealed several factors of importance, including the role of the church as an access point for testing in low-income neighbourhoods, challenges in openly discussing the relationship between sexuality and HIV, and buy-in among church leadership. These findings can support intervention development and necessitate situating African American church-based HIV testing and linkage to care interventions within a multi-level framework.

Dense genetic linkage maps of three Populus species (Populus deltoides, P. nigra and P. trichocarpa) based on AFLP and microsatellite markers.

PubMed

Cervera, M T; Storme, V; Ivens, B; Gusmão, J; Liu, B H; Hostyn, V; Van Slycken, J; Van Montagu, M; Boerjan, W

2001-06-01

Populus deltoides, P. nigra, and P. trichocarpa are the most important species for poplar breeding programs worldwide. In addition, Populus has become a model for fundamental research on trees. Linkage maps were constructed for these three species by analyzing progeny of two controlled crosses sharing the same female parent, Populus deltoides cv. S9-2 x P. nigra cv. Ghoy and P. deltoides cv. S9-2 x P. trichocarpa cv. V24. The two-way pseudotestcross mapping strategy was used to construct the maps. Amplified fragment length polymorphism (AFLP) markers that segregated 1:1 were used to form the four parental maps. Microsatellites and sequence-tagged sites were used to align homoeologous groups between the maps and to merge linkage groups within the individual maps. Linkage analysis and alignment of the homoeologous groups resulted in 566 markers distributed over 19 groups for P. deltoides covering 86% of the genome, 339 markers distributed over 19 groups for P. trichocarpa covering 73%, and 369 markers distributed over 28 groups for P. nigra covering 61%. Several tests for randomness showed that the AFLP markers were randomly distributed over the genome.

Dense genetic linkage maps of three Populus species (Populus deltoides, P. nigra and P. trichocarpa) based on AFLP and microsatellite markers.

PubMed Central

Cervera, M T; Storme, V; Ivens, B; Gusmão, J; Liu, B H; Hostyn, V; Van Slycken, J; Van Montagu, M; Boerjan, W

2001-01-01

Populus deltoides, P. nigra, and P. trichocarpa are the most important species for poplar breeding programs worldwide. In addition, Populus has become a model for fundamental research on trees. Linkage maps were constructed for these three species by analyzing progeny of two controlled crosses sharing the same female parent, Populus deltoides cv. S9-2 x P. nigra cv. Ghoy and P. deltoides cv. S9-2 x P. trichocarpa cv. V24. The two-way pseudotestcross mapping strategy was used to construct the maps. Amplified fragment length polymorphism (AFLP) markers that segregated 1:1 were used to form the four parental maps. Microsatellites and sequence-tagged sites were used to align homoeologous groups between the maps and to merge linkage groups within the individual maps. Linkage analysis and alignment of the homoeologous groups resulted in 566 markers distributed over 19 groups for P. deltoides covering 86% of the genome, 339 markers distributed over 19 groups for P. trichocarpa covering 73%, and 369 markers distributed over 28 groups for P. nigra covering 61%. Several tests for randomness showed that the AFLP markers were randomly distributed over the genome. PMID:11404342

Identifying common pressure pathways from a complex network of human activities to support ecosystem-based management.

PubMed

Knights, Antony M; Koss, Rebecca S; Robinson, Leonie A

2013-06-01

The marine environment is heavily exploited, but unintentional consequences cause wide-ranging negative effects to its characteristics. Linkage frameworks (e.g., DPSIR [driver-pressure-state-impact-response]) are commonly used to describe an interaction between human activities and ecological characteristics of the ecosystem, but as each linkage is viewed independently, the diversity of pressures that affect those characteristics may not be identified or managed effectively. Here we demonstrate an approach for using linkages to build a simple network to capture the complex relationships arising from multiple sectors and their activities. Using data-analysis tools common to ecology, we show how linkages can be placed into mechanistically similar groups. Management measures can be combined into fewer and more simplified measures that target groups of pressures rather than individual pressures, which is likely to increase compliance and the success of the measure while reducing the cost of enforcement. Given that conservation objectives (regional priorities) can vary, we also demonstrate by way of a case study example from the Marine Strategy Framework Directive, how management priorities might change, and illustrate how the approach can be used to identify sectors for control that best support the conservation objectives.

STAG3 truncating variant as the cause of primary ovarian insufficiency

PubMed Central

Le Quesne Stabej, Polona; Williams, Hywel J; James, Chela; Tekman, Mehmet; Stanescu, Horia C; Kleta, Robert; Ocaka, Louise; Lescai, Francesco; Storr, Helen L; Bitner-Glindzicz, Maria; Bacchelli, Chiara; Conway, Gerard S

2016-01-01

Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. POI is heterogeneous with only a few causative genes having been discovered so far. Our objective was to determine the genetic cause of POI in a consanguineous Lebanese family with two affected sisters presenting with primary amenorrhoea and an absence of any pubertal development. Multipoint parametric linkage analysis was performed. Whole-exome sequencing was done on the proband. Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family. Exome sequencing combined with linkage analyses offers a powerful tool to efficiently find novel genetic causes of rare, heterogeneous disorders, even in small single families. This is only the second report of a STAG3 variant; the first STAG3 variant was recently described in a phenotypically similar family with extreme POI. Identification of an additional family highlights the importance of STAG3 in POI pathogenesis and suggests it should be evaluated in families affected with POI. PMID:26059840

Potential linkage for schizophrenia on chromosome 22q12-q13: A replication study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwab, S.G.; Bondy, B.; Wildenauer, D.B.

1995-10-09

In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al., we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Z{sub max} = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a nonparametric method, sibmore » pair analysis, a P value of 0.068 corresponding to a lod score of 0.48 was obtained for this marker. This finding, together with those of Pulver et al., is suggestive of a genetic factor in this region, predisposing for schizophrenia in a subset of families. Further studies using nonparametric methods should be conducted in order to clarify this point. 32 refs., 1 fig., 4 tabs.« less

Novel splice mutation in microthalmia-associated transcription factor in Waardenburg Syndrome.

PubMed

Brenner, Laura; Burke, Kelly; Leduc, Charles A; Guha, Saurav; Guo, Jiancheng; Chung, Wendy K

2011-01-01

Waardenburg Syndrome (WS) is a syndromic form of hearing loss associated with mutations in six different genes. We identified a large family with WS that had previously undergone clinical testing, with no reported pathogenic mutation. Using linkage analysis, a region on 3p14.1 with an LOD score of 6.6 was identified. Microthalmia-Associated Transcription Factor, a gene known to cause WS, is located within this region of linkage. Sequencing of Microthalmia-Associated Transcription Factor demonstrated a c.1212 G>A synonymous variant that segregated with the WS in the family and was predicted to cause a novel splicing site that was confirmed with expression analysis of the mRNA. This case illustrates the need to computationally analyze novel synonymous sequence variants for possible effects on splicing to maximize the clinical sensitivity of sequence-based genetic testing.

Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease: Utility and Limitations

PubMed Central

Zhao, Xiao; Paterson, Andrew D.; Zahirieh, Alireza; He, Ning; Wang, Kairong; Pei, York

2008-01-01

Background and objectives: Gene-based mutation screening is now available and has the potential to provide diagnostic confirmation or exclusion of autosomal dominant polycystic kidney disease. This study illustrates its utility and limitations in the clinical setting. Design, setting, participants, & measurements: Using a molecular diagnostic service, genomic DNA of one affected individual from each study family was screened for pathologic PKD1 and PKD2 mutations. Bidirectional sequencing was performed to identify sequence variants in all exons and splice junctions of both genes and to confirm the specific mutations in other family members. In two multiplex families, microsatellite markers were genotyped at both PDK1 and PKD2 loci, and pair-wise and multipoint linkage analysis was performed. Results: Three of five probands studied were referred for assessment of renal cystic disease without a family history of autosomal dominant polycystic kidney disease, and two others were younger at-risk members of families with autosomal dominant polycystic kidney disease being evaluated as living-related kidney donors. Gene-based mutation screening identified pathogenic mutations that provided confirmation or exclusion of disease in three probands, but in the other two, only unclassified variants were identified. In one proband in which mutation screening was indeterminate, DNA linkage studies provided strong evidence for disease exclusion. Conclusions: Gene-based mutation screening or DNA linkage analysis should be considered in individuals in whom the diagnosis of autosomal dominant polycystic kidney disease is uncertain because of a lack of family history or equivocal imaging results and in younger at-risk individuals who are being evaluated as living-related kidney donors. PMID:18077784

Mapping heritability and molecular genetic associations with cortical features using probabilistic brain atlases: methods and applications to schizophrenia.

PubMed

Cannon, Tyrone D; Thompson, Paul M; van Erp, Theo G M; Huttunen, Matti; Lonnqvist, Jouko; Kaprio, Jaakko; Toga, Arthur W

2006-01-01

There is an urgent need to decipher the complex nature of genotype-phenotype relationships within the multiple dimensions of brain structure and function that are compromised in neuropsychiatric syndromes such as schizophrenia. Doing so requires sophisticated methodologies to represent population variability in neural traits and to probe their heritable and molecular genetic bases. We have recently developed and applied computational algorithms to map the heritability of, as well as genetic linkage and association to, neural features encoded using brain imaging in the context of three-dimensional (3D), populationbased, statistical brain atlases. One set of algorithms builds on our prior work using classical twin study methods to estimate heritability by fitting biometrical models for additive genetic, unique, and common environmental influences. Another set of algorithms performs regression-based (Haseman-Elston) identical-bydescent linkage analysis and genetic association analysis of DNA polymorphisms in relation to neural traits of interest in the same 3D population-based brain atlas format. We demonstrate these approaches using samples of healthy monozygotic (MZ) and dizygotic (DZ) twin pairs, as well as MZ and DZ twin pairs discordant for schizophrenia, but the methods can be generalized to other classes of relatives and to other diseases. The results confirm prior evidence of genetic influences on gray matter density in frontal brain regions. They also provide converging evidence that the chromosome 1q42 region is relevant to schizophrenia by demonstrating linkage and association of markers of the Transelin-Associated-Factor-X and Disrupted-In- Schizophrenia-1 genes with prefrontal cortical gray matter deficits in twins discordant for schizophrenia.

Linkage analysis of idiopathic generalized epilepsy (IGE) and marker loci on chromosome 6p in families of patients with juvenile myocloni epilepsy: No evidence for an epilepsy locus in the HLA region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitehouse, W.P.; Rees, M.; Curtis, D.

1993-09-01

Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisposing to idiopathic generalized epilepsy (IGE) in the families of patients with juvenile myoclonic epilepsy (JME) has been obtained in two previous studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Family members were typed for eight polymorphic loci on chromosome 6p: F13A, D6889, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise and multipoint linkage analysis was carried out assuming autosomal dominant and autosomal recessivemore » inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained at any locus. Multipoint linkage analysis generated significant exclusion data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assumed. These observations indicate that genetic heterogeneity exists within this epilepsy phenotype. 39 refs., 4 figs., 2 tabs.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

May, M.; Schwartz, C.; Huston, S.

The Opitz GBBB syndrome (OS) is characterized in part by widely spaced inner ocular canthi and hypospadias. Recently, linkage analysis showed that the gene for the X-linked form to be located in an 18 cM region spanning Xp22. We have now conducted linkage analysis in a family previously published as having the BBB syndrome and found tight linkage to DXS7104 (Z = 3.3, {theta} = 0.0). Our data narrows the candidate region to 4 cM and should facilitate the identification and characterization of one of the genes involved in midline development. 21 refs., 1 fig., 1 tab.

A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).

PubMed

Thameem, Farook; Igo, Robert P; Freedman, Barry I; Langefeld, Carl; Hanson, Robert L; Schelling, Jeffrey R; Elston, Robert C; Duggirala, Ravindranath; Nicholas, Susanne B; Goddard, Katrina A B; Divers, Jasmin; Guo, Xiuqing; Ipp, Eli; Kimmel, Paul L; Meoni, Lucy A; Shah, Vallabh O; Smith, Michael W; Winkler, Cheryl A; Zager, Philip G; Knowler, William C; Nelson, Robert G; Pahl, Madeline V; Parekh, Rulan S; Kao, W H Linda; Rasooly, Rebekah S; Adler, Sharon G; Abboud, Hanna E; Iyengar, Sudha K; Sedor, John R

2013-01-01

Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR. Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula. The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN.

A Genome-Wide Search for Linkage of Estimated Glomerular Filtration Rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND)

PubMed Central

Thameem, Farook; Igo, Robert P.; Freedman, Barry I.; Langefeld, Carl; Hanson, Robert L.; Schelling, Jeffrey R.; Elston, Robert C.; Duggirala, Ravindranath; Nicholas, Susanne B.; Goddard, Katrina A. B.; Divers, Jasmin; Guo, Xiuqing; Ipp, Eli; Kimmel, Paul L.; Meoni, Lucy A.; Shah, Vallabh O.; Smith, Michael W.; Winkler, Cheryl A.; Zager, Philip G.; Knowler, William C.; Nelson, Robert G.; Pahl, Madeline V.; Parekh, Rulan S.; Kao, W. H. Linda; Rasooly, Rebekah S.; Adler, Sharon G.; Abboud, Hanna E.; Iyengar, Sudha K.; Sedor, John R.

2013-01-01

Objective Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR. Methods Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Results The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4×10−5) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5×10−4) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5×10−4) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. Conclusion The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN. PMID:24358131

Linkage maps of the Atlantic salmon (Salmo salar) genome derived from RAD sequencing

PubMed Central

2014-01-01

Background Genetic linkage maps are useful tools for mapping quantitative trait loci (QTL) influencing variation in traits of interest in a population. Genotyping-by-sequencing approaches such as Restriction-site Associated DNA sequencing (RAD-Seq) now enable the rapid discovery and genotyping of genome-wide SNP markers suitable for the development of dense SNP linkage maps, including in non-model organisms such as Atlantic salmon (Salmo salar). This paper describes the development and characterisation of a high density SNP linkage map based on SbfI RAD-Seq SNP markers from two Atlantic salmon reference families. Results Approximately 6,000 SNPs were assigned to 29 linkage groups, utilising markers from known genomic locations as anchors. Linkage maps were then constructed for the four mapping parents separately. Overall map lengths were comparable between male and female parents, but the distribution of the SNPs showed sex-specific patterns with a greater degree of clustering of sire-segregating SNPs to single chromosome regions. The maps were integrated with the Atlantic salmon draft reference genome contigs, allowing the unique assignment of ~4,000 contigs to a linkage group. 112 genome contigs mapped to two or more linkage groups, highlighting regions of putative homeology within the salmon genome. A comparative genomics analysis with the stickleback reference genome identified putative genes closely linked to approximately half of the ordered SNPs and demonstrated blocks of orthology between the Atlantic salmon and stickleback genomes. A subset of 47 RAD-Seq SNPs were successfully validated using a high-throughput genotyping assay, with a correspondence of 97% between the two assays. Conclusions This Atlantic salmon RAD-Seq linkage map is a resource for salmonid genomics research as genotyping-by-sequencing becomes increasingly common. This is aided by the integration of the SbfI RAD-Seq SNPs with existing reference maps and the draft reference genome, as well as the identification of putative genes proximal to the SNPs. Differences in the distribution of recombination events between the sexes is evident, and regions of homeology have been identified which are reflective of the recent salmonid whole genome duplication. PMID:24571138

Mapping of a possible X-linked form of familial developmental dysphasia (FDD) in a single large pedigree

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunne, P.W.; Doody, R.S.; Epstein, H.F.

Children diagnosed with developmental dysphasia develop speech very late without exhibiting sensory or motor dysfunction, and when they do begin to speak their grammar is abnormal. A large three-generation British pedigree was recently identified in which 16 out of 30 members were diagnosed as dysphasic. Assuming a dominant mode of inheritance with homogeneous phenotypic expression and complete penetrance among affected members, we showed by simulation analysis that this pedigree has the power to detect linkage to marker loci with an average maximum LOD score of 3.67 at {theta}=0.1. Given the absence of male-to-male transmission and a ratio of female tomore » male affecteds (10/6) in this pedigree within the expected range for an X-linked dominant mode of inheritance, we decided to begin a genome-wide linkage analysis with microsatellite markers on the human X chromosome. Fifteen individuals (10 affected) from three generations were genotyped with 35 polymorphic STS`s (Research Genetics) which were approximately uniformly distributed along the X chromosome. Two-point linkage was assessed using the MLINK and ILINK programs from the LINKAGE package. Markers DXS1223, DXS987, DXS996 and DXS1060 on Xp22 showed consistent linkage to the disease locus with a maximum LOD score of 0.86 at a distance of 22 cM for DXS1060. If further analysis with additional markers and additional family members confirms X-linkage, such a localization would provide support for Lehrke`s hypothesis for X-linkage of major intellectual traits including verbal functioning.« less

Construction of high-quality recombination maps with low-coverage genomic sequencing for joint linkage analysis in maize

USDA-ARS?s Scientific Manuscript database

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...

Linkage analysis of systolic blood pressure: a score statistic and computer implementation

PubMed Central

Wang, Kai; Peng, Yingwei

2003-01-01

A genome-wide linkage analysis was conducted on systolic blood pressure using a score statistic. The randomly selected Replicate 34 of the simulated data was used. The score statistic was applied to the sibships derived from the general pedigrees. An add-on R program to GENEHUNTER was developed for this analysis and is freely available. PMID:14975145

Analysis of sulfidic linkages formed in natural rubber latex medical gloves by using X-ray absorption near edge structure

NASA Astrophysics Data System (ADS)

Chankrachang, M.; Limphirat, W.; Yongyingsakthavorn, P.; Nontakaew, U.; Tohsan, A.

2017-09-01

A study of sulfidic linkages formed in natural rubber (NR) latex medical gloves by using X-ray Absorption Near Edge Structure (XANES) is presented in this paper. The NR latex compound was prepared by using prevulcanization method, that is, it was prevulcanized at room temperature for 24 hrs before utilization. After the 24 hrs of prevulcanization, the latex film samples were obtained by dipping process. The dipped films were subjected to vulcanize at 110°C for 5 to 25 min. It was observed that after the compound was prevulcanized for 24 hrs, polysulfidic linkages were mainly formed in the sample. It was however found that after curing at 110°C for 5-25 min, the polysulfidic linkages are tended to change into disulfide linkages. Especially, in the case of 25 minutes cured sample, disulfide linkages are found to be the main linkages. In term of tensile strength, it was observed that when cure time increased from 5 - 10 min, tensile strengths were also increased. But when the cure time of the film is 25 minutes, tensile strength was slightly dropped. The dropped of tensile strength when cure time is longer than 10 minutes can be ascribed to a degradation of polysulfidic and disulfidic linkages during curing. Therefore, by using XANES analysis, it was found to be very useful to understand the cure characteristic, thus it can be very helpful to optimize cure time and tensile properties of the product.

Can statistical linkage of missing variables reduce bias in treatment effect estimates in comparative effectiveness research studies?

PubMed

Crown, William; Chang, Jessica; Olson, Melvin; Kahler, Kristijan; Swindle, Jason; Buzinec, Paul; Shah, Nilay; Borah, Bijan

2015-09-01

Missing data, particularly missing variables, can create serious analytic challenges in observational comparative effectiveness research studies. Statistical linkage of datasets is a potential method for incorporating missing variables. Prior studies have focused upon the bias introduced by imperfect linkage. This analysis uses a case study of hepatitis C patients to estimate the net effect of statistical linkage on bias, also accounting for the potential reduction in missing variable bias. The results show that statistical linkage can reduce bias while also enabling parameter estimates to be obtained for the formerly missing variables. The usefulness of statistical linkage will vary depending upon the strength of the correlations of the missing variables with the treatment variable, as well as the outcome variable of interest.

Base-Catalyzed Linkage Isomerization: An Undergraduate Inorganic Kinetics Experiment.

ERIC Educational Resources Information Center

Jackson, W. G.; And Others

1981-01-01

Describes kinetics experiments completed in a single two-hour laboratory period at 25 degrees Centigrade of nitrito to nitro rearrangement, based on the recently discovered base-catalysis path. Includes information on synthesis and characterization of linkage isomers, spectrophotometric techniques, and experimental procedures. (SK)

Genetic Map Construction and Quantitative Trait Locus (QTL) Detection of Growth-Related Traits in Litopenaeus vannamei for Selective Breeding Applications

PubMed Central

Andriantahina, Farafidy; Liu, Xiaolin; Huang, Hao

2013-01-01

Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL) have been regarded as useful for marker-assisted selection (MAS) in complex traits as growth. Using an intermediate F2 cross of slow and fast growth parents, a genetic linkage map of Pacific whiteleg shrimp, Litopenaeusvannamei , based on amplified fragment length polymorphisms (AFLP) and simple sequence repeats (SSR) markers was constructed. Meanwhile, QTL analysis was performed for growth-related traits. The linkage map consisted of 451 marker loci (429 AFLPs and 22 SSRs) which formed 49 linkage groups with an average marker space of 7.6 cM; they spanned a total length of 3627.6 cM, covering 79.50% of estimated genome size. 14 QTLs were identified for growth-related traits, including three QTLs for body weight (BW), total length (TL) and partial carapace length (PCL), two QTLs for body length (BL), one QTL for first abdominal segment depth (FASD), third abdominal segment depth (TASD) and first abdominal segment width (FASW), which explained 2.62 to 61.42% of phenotypic variation. Moreover, comparison of linkage maps between L . vannamei and Penaeus japonicus was applied, providing a new insight into the genetic base of QTL affecting the growth-related traits. The new results will be useful for conducting MAS breeding schemes in L . vannamei . PMID:24086466

Linkages and Interactions Analysis of Major Effect Drought Grain Yield QTLs in Rice.

PubMed

Vikram, Prashant; Swamy, B P Mallikarjuna; Dixit, Shalabh; Trinidad, Jennylyn; Sta Cruz, Ma Teresa; Maturan, Paul C; Amante, Modesto; Kumar, Arvind

2016-01-01

Quantitative trait loci conferring high grain yield under drought in rice are important genomic resources for climate resilient breeding. Major and consistent drought grain yield QTLs usually co-locate with flowering and/or plant height QTLs, which could be due to either linkage or pleiotropy. Five mapping populations used for the identification of major and consistent drought grain yield QTLs underwent multiple-trait, multiple-interval mapping test (MT-MIM) to estimate the significance of pleiotropy effects. Results indicated towards possible linkages between the drought grain yield QTLs with co-locating flowering and/or plant height QTLs. Linkages of days to flowering and plant height were eliminated through a marker-assisted breeding approach. Drought grain yield QTLs also showed interaction effects with flowering QTLs. Drought responsiveness of the flowering locus on chromosome 3 (qDTY3.2) has been revealed through allelic analysis. Considering linkage and interaction effects associated with drought QTLs, a comprehensive marker-assisted breeding strategy was followed to develop rice genotypes with improved grain yield under drought stress.

Limited privacy protection and poor sensitivity: Is it time to move on from the statistical linkage key-581?

PubMed

Randall, Sean M; Ferrante, Anna M; Boyd, James H; Brown, Adrian P; Semmens, James B

2016-08-01

The statistical linkage key (SLK-581) is a common tool for record linkage in Australia, due to its ability to provide some privacy protection. However, newer privacy-preserving approaches may provide greater privacy protection, while allowing high-quality linkage. To evaluate the standard SLK-581, encrypted SLK-581 and a newer privacy-preserving approach using Bloom filters, in terms of both privacy and linkage quality. Linkage quality was compared by conducting linkages on Australian health datasets using these three techniques and examining results. Privacy was compared qualitatively in relation to a series of scenarios where privacy breaches may occur. The Bloom filter technique offered greater privacy protection and linkage quality compared to the SLK-based method commonly used in Australia. The adoption of new privacy-preserving methods would allow both greater confidence in research results, while significantly improving privacy protection. © The Author(s) 2016.

PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

PubMed Central

Purcell, Shaun ; Neale, Benjamin ; Todd-Brown, Kathe ; Thomas, Lori ; Ferreira, Manuel A. R. ; Bender, David ; Maller, Julian ; Sklar, Pamela ; de Bakker, Paul I. W. ; Daly, Mark J. ; Sham, Pak C. 

2007-01-01

Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis. PMID:17701901

Testing for linkage disequilibrium in the New Zealand radiata pine breeding population

Treesearch

S. Kumar; Craig Echt; P.L. Wilcox; T.E. Richardson

2004-01-01

Linkage analysis is commonly uscd to find marker-trait associations within the full-sib families of forest tree and other species. Study of marker-trait associations at the population level is termed linkage-disequilibrium (LD) mapping. A female-tester design comprising 200 full-sib families generated by crossing 40 pollen parents with five female parents was used to...

Linkages to Public Land Framework: toward embedding humans in ecosystem analyses by using “inside-out social assessment.”

Treesearch

Joanna Endter-Wada; Dale J. Blahna

2011-01-01

This article presents the " Linkages to Public Land" (LPL) Framework, a general but comprehensive data-gathering and analysis approach aimed at informing citizen and agency decision making about the social environment of public land. This social assessment and planning approach identifies and categorizes various types of linkages that people have to public...

A basis for translational cancer research on aetiology, pathogenesis and prognosis: Guideline for standardised and population-based linkages of biobanks to cancer registries.

PubMed

Dillner, Joakim

2015-06-01

Population-based cancer research is paramount for controlling cancer. Cancer research is increasingly dependent on access to biospecimens from subjects that have been followed-up for future health outcomes. This is achieved using longitudinal follow-up of cohorts and biobanks using cancer registry linkages. All over the world, more and more large population-based cohorts and advanced biobanking facilities are established. International standardisation and networking in the linkage of cohorts and biobanks to cancer registries is required in order to enable international cancer research and comparability of research results. An international operating procedure and standard minimum dataset for linkages of biobanks, cohorts and cancer registries is proposed. An internationally comparable provision of well characterised study bases for molecular cancer research will be an essential prerequisite for the success of translational medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis and compensation of an aircraft simulator control loading system with compliant linkage. [using hydraulic equipment

NASA Technical Reports Server (NTRS)

Johnson, P. R.; Bardusch, R. E.

1974-01-01

A hydraulic control loading system for aircraft simulation was analyzed to find the causes of undesirable low frequency oscillations and loading effects in the output. The hypothesis of mechanical compliance in the control linkage was substantiated by comparing the behavior of a mathematical model of the system with previously obtained experimental data. A compensation scheme based on the minimum integral of the squared difference between desired and actual output was shown to be effective in reducing the undesirable output effects. The structure of the proposed compensation was computed by use of a dynamic programing algorithm and a linear state space model of the fixed elements in the system.

Improving record linkage performance in the presence of missing linkage data.

PubMed

Ong, Toan C; Mannino, Michael V; Schilling, Lisa M; Kahn, Michael G

2014-12-01

Existing record linkage methods do not handle missing linking field values in an efficient and effective manner. The objective of this study is to investigate three novel methods for improving the accuracy and efficiency of record linkage when record linkage fields have missing values. By extending the Fellegi-Sunter scoring implementations available in the open-source Fine-grained Record Linkage (FRIL) software system we developed three novel methods to solve the missing data problem in record linkage, which we refer to as: Weight Redistribution, Distance Imputation, and Linkage Expansion. Weight Redistribution removes fields with missing data from the set of quasi-identifiers and redistributes the weight from the missing attribute based on relative proportions across the remaining available linkage fields. Distance Imputation imputes the distance between the missing data fields rather than imputing the missing data value. Linkage Expansion adds previously considered non-linkage fields to the linkage field set to compensate for the missing information in a linkage field. We tested the linkage methods using simulated data sets with varying field value corruption rates. The methods developed had sensitivity ranging from .895 to .992 and positive predictive values (PPV) ranging from .865 to 1 in data sets with low corruption rates. Increased corruption rates lead to decreased sensitivity for all methods. These new record linkage algorithms show promise in terms of accuracy and efficiency and may be valuable for combining large data sets at the patient level to support biomedical and clinical research. Copyright © 2014 Elsevier Inc. All rights reserved.

Three-dimensional structural dynamics of DNA origami Bennett linkages using individual-particle electron tomography

DOE PAGES

Lei, Dongsheng; Marras, Alexander E.; Liu, Jianfang; ...

2018-02-09

Scaffolded DNA origami has proven to be a powerful and efficient technique to fabricate functional nanomachines by programming the folding of a single-stranded DNA template strand into three-dimensional (3D) nanostructures, designed to be precisely motion-controlled. Although two-dimensional (2D) imaging of DNA nanomachines using transmission electron microscopy and atomic force microscopy suggested these nanomachines are dynamic in 3D, geometric analysis based on 2D imaging was insufficient to uncover the exact motion in 3D. In this paper, we use the individual-particle electron tomography method and reconstruct 129 density maps from 129 individual DNA origami Bennett linkage mechanisms at ~6-14 nm resolution. The statisticalmore » analyses of these conformations lead to understanding the 3D structural dynamics of Bennett linkage mechanisms. Moreover, our effort provides experimental verification of a theoretical kinematics model of DNA origami, which can be used as feedback to improve the design and control of motion via optimized DNA sequences and routing.« less

Three-dimensional structural dynamics of DNA origami Bennett linkages using individual-particle electron tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lei, Dongsheng; Marras, Alexander E.; Liu, Jianfang

Scaffolded DNA origami has proven to be a powerful and efficient technique to fabricate functional nanomachines by programming the folding of a single-stranded DNA template strand into three-dimensional (3D) nanostructures, designed to be precisely motion-controlled. Although two-dimensional (2D) imaging of DNA nanomachines using transmission electron microscopy and atomic force microscopy suggested these nanomachines are dynamic in 3D, geometric analysis based on 2D imaging was insufficient to uncover the exact motion in 3D. In this paper, we use the individual-particle electron tomography method and reconstruct 129 density maps from 129 individual DNA origami Bennett linkage mechanisms at ~6-14 nm resolution. The statisticalmore » analyses of these conformations lead to understanding the 3D structural dynamics of Bennett linkage mechanisms. Moreover, our effort provides experimental verification of a theoretical kinematics model of DNA origami, which can be used as feedback to improve the design and control of motion via optimized DNA sequences and routing.« less

Unraveling the Structural Modifications in Lignin of Arundo donax Linn. during Acid-Enhanced Ionic Liquid Pretreatment.

PubMed

You, Tingting; Zhang, Liming; Guo, Siqin; Shao, Lupeng; Xu, Feng

2015-12-23

Solid acid-enhanced ionic liquid (IL) pretreatment is of paramount importance for boosting the yield of sugars from biomass cost-effectively and environmentally friendly. To unravel the chemical and supramolecular structural changes of lignin after pretreatment, IL-acid lignin (ILAL) and subsequent residual cellulolytic enzyme lignin (RCEL) were isolated from Arundo donax Linn. The structural features were compared with those of the corresponding milled wood lignin (MWL). Results indicated that the pretreatment caused loss of β-O-4', β-β', β-1' linkages and formation of condensed structures in lignin. A preferential breakdown of G-type lignin may have occurred, evidenced by an increased S/G ratio revealed by 2D HSQC NMR analysis. It was determined that the depolymerization of β-O-4' linkage, lignin recondensation, and cleavage of ferulate-lignin ether linkages took place. Moreover, a simulation module was first developed to define morphological changes in lignin based on AFM and TEM analyses. Briefly, tree branch like aggregates was destroyed to monodisperse particles.

Fine-mapping of qGW4.05, a major QTL for kernel weight and size in maize.

PubMed

Chen, Lin; Li, Yong-xiang; Li, Chunhui; Wu, Xun; Qin, Weiwei; Li, Xin; Jiao, Fuchao; Zhang, Xiaojing; Zhang, Dengfeng; Shi, Yunsu; Song, Yanchun; Li, Yu; Wang, Tianyu

2016-04-12

Kernel weight and size are important components of grain yield in cereals. Although some information is available concerning the map positions of quantitative trait loci (QTL) for kernel weight and size in maize, little is known about the molecular mechanisms of these QTLs. qGW4.05 is a major QTL that is associated with kernel weight and size in maize. We combined linkage analysis and association mapping to fine-map and identify candidate gene(s) at qGW4.05. QTL qGW4.05 was fine-mapped to a 279.6-kb interval in a segregating population derived from a cross of Huangzaosi with LV28. By combining the results of regional association mapping and linkage analysis, we identified GRMZM2G039934 as a candidate gene responsible for qGW4.05. Candidate gene-based association mapping was conducted using a panel of 184 inbred lines with variable kernel weights and kernel sizes. Six polymorphic sites in the gene GRMZM2G039934 were significantly associated with kernel weight and kernel size. The results of linkage analysis and association mapping revealed that GRMZM2G039934 is the most likely candidate gene for qGW4.05. These results will improve our understanding of the genetic architecture and molecular mechanisms underlying kernel development in maize.

Linkage analysis of the Nail-patella syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campeau, E.; Watkins, D.; Rouleau, G.A.

1995-01-01

Nail-patella syndrome (NPS) is an autosomal dominant disorder characterized by dysplasia of nails and patella, decreased mobility of the elbow, iliac horns, and, in some cases, nephropathy. The disorder has been mapped to the long arm of chromosome 9, but the precise localization and identity of the NPS gene are unknown. Linkage analysis in three NPS families, using highly informative dinucleotide repeat polymorphisms on 9q33-q34, confirmed linkage of NPS to this chromosome. Recombinations were detected, by two-point linkage analysis, between NPS and the centromeric markers D9S60 and the gelsolin gene and the telomeric markers D9S64 and D9S66, in one ofmore » the families. Haplotype analysis suggested an additional recombination between NPS and the argininosuccinate synthetase (ASS) gene. These results localize the NPS gene to an interval on 9q34.1, distal to D9S60 an proximal to ASS, comprising a genetic distance of {approximately}9 cM. This represents a significant refinement in the localization of the NPS gene. 25 refs., 2 figs., 1 tab.« less

Use of Multivariate Linkage Analysis for Dissection of a Complex Cognitive Trait

PubMed Central

Marlow, Angela J.; Fisher, Simon E.; Francks, Clyde; MacPhie, I. Laurence; Cherny, Stacey S.; Richardson, Alex J.; Talcott, Joel B.; Stein, John F.; Monaco, Anthony P.; Cardon, Lon R.

2003-01-01

Replication of linkage results for complex traits has been exceedingly difficult, owing in part to the inability to measure the precise underlying phenotype, small sample sizes, genetic heterogeneity, and statistical methods employed in analysis. Often, in any particular study, multiple correlated traits have been collected, yet these have been analyzed independently or, at most, in bivariate analyses. Theoretical arguments suggest that full multivariate analysis of all available traits should offer more power to detect linkage; however, this has not yet been evaluated on a genomewide scale. Here, we conduct multivariate genomewide analyses of quantitative-trait loci that influence reading- and language-related measures in families affected with developmental dyslexia. The results of these analyses are substantially clearer than those of previous univariate analyses of the same data set, helping to resolve a number of key issues. These outcomes highlight the relevance of multivariate analysis for complex disorders for dissection of linkage results in correlated traits. The approach employed here may aid positional cloning of susceptibility genes in a wide spectrum of complex traits. PMID:12587094

[A network to promote health systems based on primary health care in the Region of the Americas].

PubMed

Herrera Vázquez, María Magdalena; Rodríguez Avila, Nuria; Nebot Adell, Carme; Montenegro, Hernán

2007-05-01

To identify the relational components of an international network of organizations that provide technical and financial assistance to promote the development of health systems based on primary health care in the countries of the Region of the Americas; to analyze the linkages that would allow the collaborating partners of the Pan American Health Organization (PAHO) to work together on health issues; and to determine the basic theoretical elements that can help to develop action strategies that support advocacy efforts by a network. This was a qualitative and quantitative cross-sectional study based on identifying key informants and on analyzing social networks. Ethnographic and relational information from 46 international organizations was collected through a self-administered semistructured questionnaire. From 46 international health cooperation organizations, 29 decision makers from 29 organizations participated (63.0% response rate). The structure and the strength of the network was evaluated in terms of density, closeness, clustering, and centralization. The statistical analysis was done using computer programs that included UCINET, Pajek, and Microsoft Access. We found a structurally centralized theoretical network, whose nodes were clustered into four central subgroups linked by a shared vision. The leadership, influence, and political interests reflected the formal and technical-cooperation linkages, the formal support for health systems based on primary health care, and the flow of resources being more often technical ones than financial ones. The interorganizational relational components and the social-action ties that were identified could help in the development and consolidation of a thematic network for advocacy and for the management of technical and financial assistance that supports primary health care in the Americas. The linkages for joint action that were identified could advance international cooperation in developing health systems based on primary health care, once PAHO formulates clear implementation strategies and takes a leadership position in mobilizing financial resources and in creating informal and interpersonal linkages for action.

Tests for linkage and association in nuclear families.

PubMed Central

Martin, E R; Kaplan, N L; Weir, B S

1997-01-01

The transmission/disequilibrium test (TDT) originally was introduced to test for linkage between a genetic marker and a disease-susceptibility locus, in the presence of association. Recently, the TDT has been used to test for association in the presence of linkage. The motivation for this is that linkage analysis typically identifies large candidate regions, and further refinement is necessary before a search for the disease gene is begun, on the molecular level. Evidence of association and linkage may indicate which markers in the region are closest to a disease locus. As a test of linkage, transmissions from heterozygous parents to all of their affected children can be included in the TDT; however, the TDT is a valid chi2 test of association only if transmissions to unrelated affected children are used in the analysis. If the sample contains independent nuclear families with multiple affected children, then one procedure that has been used to test for association is to select randomly a single affected child from each sibship and to apply the TDT to those data. As an alternative, we propose two statistics that use data from all of the affected children. The statistics give valid chi2 tests of the null hypothesis of no association or no linkage and generally are more powerful than the TDT with a single, randomly chosen, affected child from each family. PMID:9311750

A Brassica rapa Linkage Map of EST-based SNP Markers for Identification of Candidate Genes Controlling Flowering Time and Leaf Morphological Traits

PubMed Central

Li, Feng; Kitashiba, Hiroyasu; Inaba, Kiyofumi; Nishio, Takeshi

2009-01-01

For identification of genes responsible for varietal differences in flowering time and leaf morphological traits, we constructed a linkage map of Brassica rapa DNA markers including 170 EST-based markers, 12 SSR markers, and 59 BAC sequence-based markers, of which 151 are single nucleotide polymorphism (SNP) markers. By BLASTN, 223 markers were shown to have homologous regions in Arabidopsis thaliana, and these homologous loci covered nearly the whole genome of A. thaliana. Synteny analysis between B. rapa and A. thaliana revealed 33 large syntenic regions. Three quantitative trait loci (QTLs) for flowering time were detected. BrFLC1 and BrFLC2 were linked to the QTLs for bolting time, budding time, and flowering time. Three SNPs in the promoter, which may be the cause of low expression of BrFLC2 in the early-flowering parental line, were identified. For leaf lobe depth and leaf hairiness, one major QTL corresponding to a syntenic region containing GIBBERELLIN 20 OXIDASE 3 and one major QTL containing BrGL1, respectively, were detected. Analysis of nucleotide sequences and expression of these genes suggested possible involvement of these genes in leaf morphological traits. PMID:19884167

Identification of Sialic Acid Linkages on Intact Glycopeptides via Differential Chemical Modification Using IntactGIG-HILIC

NASA Astrophysics Data System (ADS)

Yang, Shuang; Wu, Wells W.; Shen, Rong-Fong; Bern, Marshall; Cipollo, John

2018-04-01

Mass spectrometric analysis of intact glycopeptides can reveal detailed information about glycosite, glycan structural features, and their heterogeneity. Sialyl glycopeptides can be positively, negatively, or neutrally charged depending on pH of their buffer solution and ionization conditions. To detect sialoglycopeptides, a negative-ion mode mass spectrometry may be applied with a minimal loss of sialic acids, although the positively charged or neutral glycopeptides may be excluded. Alternatively, the sialyl glycopeptides can be identified using positive-ion mode analysis by doping a high concentration of sodium salts to the analytes. Although manipulation of unmodified sialoglycopeptides can be useful for analysis of samples, less than optimal ionization, facile loss of sialyl and unfavorable ionization of accompanying non-sialyl peptides make such strategies suboptimal. Currently available chemical derivatization methods, while stabilizing for sialic acid, mask sialic acid linkage configuration. Here, we report the development of a novel approach to neutralize sialic acids via sequentially chemical modification that also reveals their linkage configuration, often an important determinant in biological function. This method utilizes several components to facilitate glycopeptide identification. These include the following: solid phase derivatization, enhanced ionization of sialoglycopeptides, differentiation of sialic acid linkage, and enrichment of the modified glycopeptides by hydrophilic interaction liquid chromatography. This technology can be used as a tool for quantitative analysis of protein sialylation in diseases with determination of sialic acid linkage configuration. [Figure not available: see fulltext.

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14

PubMed Central

Etain, Bruno; Mathieu, Flavie; Rietschel, Marcella; Maier, Wolfgang; Albus, Margot; Mckeon, Patrick; Roche, S.; Kealey, Carmel; Blackwood, Douglas; Muir, Walter; Bellivier, Franc; Henry, C.; Dina, Christian; Gallina, Sophie; Gurling, H.; Malafosse, Alain; Preisig, Martin; Ferrero, François; Cichon, Sven; Schumacher, J.; Ohlraun, Stéphanie; Borrmann-Hassenbach, M.; Propping, Peter; Abou Jamra, Rami; Schulze, Thomas G.; Marusic, Andrej; Dernovsek, Mojca Z.; Giros, Bruno; Bourgeron, Thomas; Lemainque, Arnaud; Bacq, Delphine; Betard, Christine; Charon, Céline; Nöthen, Markus M.; Lathrop, Mark; Leboyer, Marion

2006-01-01

Summary Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (age at onset of 21 years or below). Non parametric multi-point analysis suggested eight regions of linkage with p-values <0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide p-value estimated over 10.000 simulated replicates of 0.015 [0.01–0.02]). After genome-wide search analysis, we performed additional linkage analyses with increase marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non parametric linkage score increased from 3.51 to 3.83. This study is the first to use early onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families. PMID:16534504

Linkage to HIV care and its determinants in the late HAART era: a systematic review and meta-analysis.

PubMed

Perelman, Julian; Rosado, Ricardo; Ferro, Adriana; Aguiar, Pedro

2018-06-01

Poor engagement into HIV care limits the effectiveness of highly active antiretroviral therapies (HAART) to improve survival and reduce transmission. The design of effective interventions to enhance linkage to care is dependent on evidence about rates of entry into HIV care. This is a systematic review and meta-analysis on linkage measurement and its determinants in the late era of HAART (post-2003), in high-income countries. We searched the PubMed and Web of Science databases, restricting our sample to the late HAART era (post-2003) until February 2016, and to high-income countries. We retained only studies that produced quantified outcomes. We rejected the studies with a high risk of bias, and followed a standard meta-analytic approach. Because there was a high heterogeneity ( I 2  > 90%), the aggregated findings were based on a random-effects model. A total of 43 studies were identified, all of them following a cohort of patients newly diagnosed until referred to specialized care. For a one-month period, the meta-proportion was 71.1% (IC95%: 61.0%-81.2). For a three-month duration, the meta-proportion of linkage to care was 77.0% (IC95%: 75.0%-79.0). For a one-year period, the meta-proportion was 76.3% (IC95%: 54.2%-98.4%). The proportions were lower when lab tests were used as referral indicator, with a pooled meta-proportion of 76.7% (IC95%: 73.0%-80.4), in comparison to a value of 80.8% (IC95%: 68.7%-92.9) for consultations. Being black or male were the most commonly observed determinants of delayed entry into care. Young people, injecting drug users, people with low socioeconomic status, or at a less advanced stage of disease also experienced lower proportions of timely linkage. Timely engagement into care is below 80% and specific sub-groups are particularly at risk of late entry. These findings confirm earlier evidence that linkage to care remains low, and that efforts should focus on vulnerable populations.

Linkage analysis of juvenile myoclonic epilepsy and microsatellite loci spanning 61 cM of human chromosome 6p in 19 nuclear pedigrees provides no evidence for a susceptibility locus in this region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elmslie, F.V.; Williamson, M.P.; Rees, M.

1996-09-01

Linkage analysis in separately ascertained families of probands with juvenile myoclonic epilepsy (JME) has previously provided evidence both for and against the existence of a locus (designated {open_quotes}EJM1{close_quotes}), on chromosome 6p, predisposing to a trait defined as either clinical JME, its associated electroencephalographic abnormality, or idiopathic generalized epilepsy. Linkage analysis was performed in 19 families in which a proband and at least one first- or two second-degree relatives have clinical JME. Family members were typed for seven highly polymorphic microsatellite markers on chromosome 6p: D6S260, D6S276, D6S291, D6S271, D6S465, D6S257, and D6S254. Pairwise and multipoint linkage analysis was carried outmore » under the assumptions of autosomal dominant inheritance at 70% and 50% penetrance and autosomal recessive inheritance at 70% and 50% penetrance. No significant evidence in favor of linkage to the clinical trait of JME was obtained for any locus. The region formally excluded (LOD score <-2) by using multipoint analysis varies depending on the assumptions made concerning inheritance parameters and the proportion of linked families, {alpha} - that is, the degree of locus heterogeneity. Further analysis either classifying all unaffected individuals as unknown or excluding a subset of four families in which pyknoleptic absence seizures were present in one or more individuals did not alter these conclusions. 24 refs., 4 figs., 1 tab.« less

Genome-wide linkage scan for maximum and length-dependent knee muscle strength in young men: significant evidence for linkage at chromosome 14q24.3.

PubMed

De Mars, G; Windelinckx, A; Huygens, W; Peeters, M W; Beunen, G P; Aerssens, J; Vlietinck, R; Thomis, M A I

2008-05-01

Maintenance of high muscular fitness is positively related to bone health, functionality in daily life and increasing insulin sensitivity, and negatively related to falls and fractures, morbidity and mortality. Heritability of muscle strength phenotypes ranges between 31% and 95%, but little is known about the identity of the genes underlying this complex trait. As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to muscle and bone cross-sectional area, isometric knee flexion and extension torque, and torque-length relationship for knee flexors and extensors. In total, 283 informative male siblings (17-36 years old), belonging to 105 families, were used to conduct a genome-wide SNP-based multipoint linkage analysis. The strongest evidence for linkage was found for the torque-length relationship of the knee flexors at 14q24.3 (LOD = 4.09; p<10(-5)). Suggestive evidence for linkage was found at 14q32.2 (LOD = 3.00; P = 0.005) for muscle and bone cross-sectional area, at 2p24.2 (LOD = 2.57; p = 0.01) for isometric knee torque at 30 degrees flexion, at 1q21.3, 2p23.3 and 18q11.2 (LOD = 2.33, 2.69 and 2.21; p<10(-4) for all) for the torque-length relationship of the knee extensors and at 18p11.31 (LOD = 2.39; p = 0.0004) for muscle-mass adjusted isometric knee extension torque. We conclude that many small contributing genes rather than a few important genes are involved in causing variation in different underlying phenotypes of muscle strength. Furthermore, some overlap in promising genomic regions were identified among different strength phenotypes.

A unique linkage of administrative and clinical registry databases to expand analytic possibilities in pediatric heart transplantation research.

PubMed

Godown, Justin; Thurm, Cary; Dodd, Debra A; Soslow, Jonathan H; Feingold, Brian; Smith, Andrew H; Mettler, Bret A; Thompson, Bryn; Hall, Matt

2017-12-01

Large clinical, research, and administrative databases are increasingly utilized to facilitate pediatric heart transplant (HTx) research. Linking databases has proven to be a robust strategy across multiple disciplines to expand the possible analyses that can be performed while leveraging the strengths of each dataset. We describe a unique linkage of the Scientific Registry of Transplant Recipients (SRTR) database and the Pediatric Health Information System (PHIS) administrative database to provide a platform to assess resource utilization in pediatric HTx. All pediatric patients (1999-2016) who underwent HTx at a hospital enrolled in the PHIS database were identified. A linkage was performed between the SRTR and PHIS databases in a stepwise approach using indirect identifiers. To determine the feasibility of using these linked data to assess resource utilization, total and post-HTx hospital costs were assessed. A total of 3188 unique transplants were identified as being present in both databases and amenable to linkage. Linkage of SRTR and PHIS data was successful in 3057 (95.9%) patients, of whom 2896 (90.8%) had complete cost data. Median total and post-HTx hospital costs were $518,906 (IQR $324,199-$889,738), and $334,490 (IQR $235,506-$498,803) respectively with significant differences based on patient demographics and clinical characteristics at HTx. Linkage of the SRTR and PHIS databases is feasible and provides an invaluable tool to assess resource utilization. Our analysis provides contemporary cost data for pediatric HTx from the largest US sample reported to date. It also provides a platform for expanded analyses in the pediatric HTx population. Copyright © 2017 Elsevier Inc. All rights reserved.

Glycoside hydrolase family 13 α-glucosidases encoded by Bifidobacterium breve UCC2003; A comparative analysis of function, structure and phylogeny.

PubMed

Kelly, Emer D; Bottacini, Francesca; O'Callaghan, John; Motherway, Mary O'Connell; O'Connell, Kerry Joan; Stanton, Catherine; van Sinderen, Douwe

2016-05-02

Bifidobacterium breve is a noted inhabitant and one of the first colonizers of the human gastro intestinal tract (GIT). The ability of this bacterium to persist in the GIT is reflected by the abundance of carbohydrate-active enzymes that are encoded by its genome. One such family of enzymes is represented by the α-glucosidases, of which three, Agl1, Agl2 and MelD, have previously been identified and characterized in the prototype B. breve strain UCC2003. In this report, we describe an additional B. breve UCC2003-encoded α-glucosidase, along with a B. breve UCC2003-encoded α-glucosidase-like protein, designated here as Agl3 and Agl4, respectively, which together with the three previously described enzymes belong to glycoside hydrolase (GH) family 13. Agl3 was shown to exhibit hydrolytic specificity towards the α-(1→6) linkage present in palatinose; the α-(1→3) linkage present in turanose; the α-(1→4) linkages found in maltotriose and maltose; and to a lesser degree, the α-(1→2) linkage found in sucrose and kojibiose; and the α-(1→5) linkage found in leucrose. Surprisingly, based on the substrates analyzed, Agl4 did not exhibit biologically relevant α-glucosidic activity. With the presence of four functionally active GH13 α-glucosidases, B. breve UCC2003 is capable of hydrolyzing all α-glucosidic linkages that can be expected in glycan substrates in the lower GIT. This abundance of α-glucosidases provides B. breve UCC2003 with an adaptive ability and metabolic versatility befitting the transient nature of growth substrates in the GIT. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic linkage map construction and QTL mapping of salt tolerance traits in Zoysiagrass (Zoysia japonica).

PubMed

Guo, Hailin; Ding, Wanwen; Chen, Jingbo; Chen, Xuan; Zheng, Yiqi; Wang, Zhiyong; Liu, Jianxiu

2014-01-01

Zoysiagrass (Zoysia Willd.) is an important warm season turfgrass that is grown in many parts of the world. Salt tolerance is an important trait in zoysiagrass breeding programs. In this study, a genetic linkage map was constructed using sequence-related amplified polymorphism markers and random amplified polymorphic DNA markers based on an F1 population comprising 120 progeny derived from a cross between Zoysia japonica Z105 (salt-tolerant accession) and Z061 (salt-sensitive accession). The linkage map covered 1211 cM with an average marker distance of 5.0 cM and contained 24 linkage groups with 242 marker loci (217 sequence-related amplified polymorphism markers and 25 random amplified polymorphic DNA markers). Quantitative trait loci affecting the salt tolerance of zoysiagrass were identified using the constructed genetic linkage map. Two significant quantitative trait loci (qLF-1 and qLF-2) for leaf firing percentage were detected; qLF-1 at 36.3 cM on linkage group LG4 with a logarithm of odds value of 3.27, which explained 13.1% of the total variation of leaf firing and qLF-2 at 42.3 cM on LG5 with a logarithm of odds value of 2.88, which explained 29.7% of the total variation of leaf firing. A significant quantitative trait locus (qSCW-1) for reduced percentage of dry shoot clipping weight was detected at 44.1 cM on LG5 with a logarithm of odds value of 4.0, which explained 65.6% of the total variation. This study provides important information for further functional analysis of salt-tolerance genes in zoysiagrass. Molecular markers linked with quantitative trait loci for salt tolerance will be useful in zoysiagrass breeding programs using marker-assisted selection.

A first linkage map of globe artichoke (Cynara cardunculus var. scolymus L.) based on AFLP, S-SAP, M-AFLP and microsatellite markers.

PubMed

Lanteri, S; Acquadro, A; Comino, C; Mauro, R; Mauromicale, G; Portis, E

2006-05-01

We present the first genetic maps of globe artichoke (Cynara cardunculus var. scolymus L. 2n=2x=34), constructed with a two-way pseudo-testcross strategy. A F1 mapping population of 94 individuals was generated between a late-maturing, non-spiny type and an early-maturing spiny type. The 30 AFLP, 13 M-AFLP and 9 S-SAP primer combinations chosen identified, respectively, 352, 38 and 41 polymorphic markers. Of 32 microsatellite primer pairs tested, 12 identified heterozygous loci in one or other parent, and 7 were fully informative as they segregated in both parents. The female parent map comprised 204 loci, spread over 18 linkage groups and spanned 1330.5 cM with a mean marker density of 6.5 cM. The equivalent figures for the male parent map were 180 loci, 17 linkage groups, 1239.4 and 6.9 cM. About 3% of the AFLP and AFLP-derived markers displayed segregation distortion with a P value below 0.01, and were not used for map construction. All the SSR loci were included in the linkage analysis, although one locus did show some segregation distortion. The presence of 78 markers in common to both maps allowed the alignment of 16 linkage groups. The maps generated provide a firm basis for the mapping of agriculturally relevant traits, which will then open the way for the application of a marker-assisted selection breeding strategy in this species.

Linkage mechanisms in the vertebrate skull: Structure and function of three-dimensional, parallel transmission systems.

PubMed

Olsen, Aaron M; Westneat, Mark W

2016-12-01

Many musculoskeletal systems, including the skulls of birds, fishes, and some lizards consist of interconnected chains of mobile skeletal elements, analogous to linkage mechanisms used in engineering. Biomechanical studies have applied linkage models to a diversity of musculoskeletal systems, with previous applications primarily focusing on two-dimensional linkage geometries, bilaterally symmetrical pairs of planar linkages, or single four-bar linkages. Here, we present new, three-dimensional (3D), parallel linkage models of the skulls of birds and fishes and use these models (available as free kinematic simulation software), to investigate structure-function relationships in these systems. This new computational framework provides an accessible and integrated workflow for exploring the evolution of structure and function in complex musculoskeletal systems. Linkage simulations show that kinematic transmission, although a suitable functional metric for linkages with single rotating input and output links, can give misleading results when applied to linkages with substantial translational components or multiple output links. To take into account both linear and rotational displacement we define force mechanical advantage for a linkage (analogous to lever mechanical advantage) and apply this metric to measure transmission efficiency in the bird cranial mechanism. For linkages with multiple, expanding output points we propose a new functional metric, expansion advantage, to measure expansion amplification and apply this metric to the buccal expansion mechanism in fishes. Using the bird cranial linkage model, we quantify the inaccuracies that result from simplifying a 3D geometry into two dimensions. We also show that by combining single-chain linkages into parallel linkages, more links can be simulated while decreasing or maintaining the same number of input parameters. This generalized framework for linkage simulation and analysis can accommodate linkages of differing geometries and configurations, enabling novel interpretations of the mechanics of force transmission across a diversity of vertebrate feeding mechanisms and enhancing our understanding of musculoskeletal function and evolution. J. Morphol. 277:1570-1583, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Linkage of Type 2 Diabetes on Chromosome 9p24 in Mexican Americans: Additional Evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)

PubMed Central

Farook, Vidya S.; Coletta, Dawn K.; Puppala, Sobha; Schneider, Jennifer; Chittoor, Geetha; Hu, Shirley L.; Winnier, Deidre A.; Norton, Luke; Dyer, Thomas D.; Arya, Rector; Cole, Shelley A.; Carless, Melanie; Göring, Harald H.; Almasy, Laura; Mahaney, Michael C.; Comuzzie, Anthony G.; Curran, Joanne E.; Blangero, John; Duggirala, Ravindranath; Lehman, Donna M.; Jenkinson, Christopher P.; DeFronzo, Ralph A.

2014-01-01

Objective Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage analysis to localize T2DM susceptibility loci in Mexican Americans. Methods We used the phenotypic and genotypic data from 1,122 Mexican American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). Genome-wide linkage analysis was performed, using the variance components approach. Data from two additional Mexican American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, P = 2.7 × 10−6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region in SAFDGS also, we found the significant and increased linkage evidence (LOD = 4.3, empirical P = 1.0 × 10−5, genome-wide P = 1.6 × 10−3) for T2DM at the same chromosomal region when we performed genome-wide linkage analysis of the VAGES data combined with SAFHS and SAFDGS data. Conclusion Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies (GWASs) involving T2DM related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes. PMID:24060607

A strabismus susceptibility locus on chromosome 7p

PubMed Central

Parikh, Vaishali; Shugart, Yin Yao; Doheny, Kimberly F.; Zhang, Jie; Li, Lan; Williams, John; Hayden, David; Craig, Brian; Capo, Hilda; Chamblee, Denise; Chen, Cathy; Collins, Mary; Dankner, Stuart; Fiergang, Dean; Guyton, David; Hunter, David; Hutcheon, Marcia; Keys, Marshall; Morrison, Nancy; Munoz, Michelle; Parks, Marshall; Plotsky, David; Protzko, Eugene; Repka, Michael X.; Sarubbi, Maria; Schnall, Bruce; Siatkowski, R. Michael; Traboulsi, Elias; Waeltermann, Joanne; Nathans, Jeremy

2003-01-01

Strabismus has been known to have a significant genetic component, but the mode of inheritance and the identity of the relevant genes have been enigmatic. This paper reports linkage analysis of nonsyndromic strabismus. The principal results of this study are: (i) the demonstrated feasibility of identifying and recruiting large families in which multiple members have (or had) strabismus; (ii) the linkage in one large family of a presumptive strabismus susceptibility locus to 7p22.1 with a multipoint logarithm of odds score of 4.51 under a model of recessive inheritance; and (iii) the failure to observe significant linkage to 7p in six other multiplex families, consistent with genetic heterogeneity among families. These findings suggest that it will be possible to localize and ultimately identify strabismus susceptibility genes by linkage analysis and mutation screening of candidate genes. PMID:14519848

Short Communication: Genetic linkage map of Cucurbita maxima with molecular and morphological markers.

PubMed

Ge, Y; Li, X; Yang, X X; Cui, C S; Qu, S P

2015-05-22

Cucurbita maxima is one of the most widely cultivated vegetables in China and exhibits distinct morphological characteristics. In this study, genetic linkage analysis with 57 simple-sequence repeats, 21 amplified fragment length polymorphisms, 3 random-amplified polymorphic DNA, and one morphological marker revealed 20 genetic linkage groups of C. maxima covering a genetic distance of 991.5 cM with an average of 12.1 cM between adjacent markers. Genetic linkage analysis identified the simple-sequence repeat marker 'PU078072' 5.9 cM away from the locus 'Rc', which controls rind color. The genetic map in the present study will be useful for better mapping, tagging, and cloning of quantitative trait loci/gene(s) affecting economically important traits and for breeding new varieties of C. maxima through marker-assisted selection.

Measuring Personal Networks and Their Relationship with Scientific Production

ERIC Educational Resources Information Center

Villanueva-Felez, Africa; Molas-Gallart, Jordi; Escribá-Esteve, Alejandro

2013-01-01

The analysis of social networks has remained a crucial and yet understudied aspect of the efforts to measure Triple Helix linkages. The Triple Helix model aims to explain, among other aspects of knowledge-based societies, "the current research system in its social context" (Etzkowitz and Leydesdorff 2000:109). This paper develops a novel…

Structured Constructs Models Based on Change-Point Analysis

ERIC Educational Resources Information Center

Shin, Hyo Jeong; Wilson, Mark; Choi, In-Hee

2017-01-01

This study proposes a structured constructs model (SCM) to examine measurement in the context of a multidimensional learning progression (LP). The LP is assumed to have features that go beyond a typical multidimentional IRT model, in that there are hypothesized to be certain cross-dimensional linkages that correspond to requirements between the…

Selective digestion of Ba2+/Ca2+ alginate gel microdroplets for single-cell handling

NASA Astrophysics Data System (ADS)

Odaka, Masao; Hattori, Akihiro; Matsuura, Kenji; Yasuda, Kenji

2018-06-01

Cells encapsuled by polymer microdroplets are an effective platform for the identification and separation of individual cells for single-cell-based analysis. However, a key challenge is to maintain and release the captured cells in the microdroplets selectively, nondestructively, and noninvasively. We developed a simple method of encapsulating cells in alginate microdroplets having different digestion characteristics. Cells were diluted with an alginate polymer of sol state and encapsulated into microdroplets with Ba2+ and Ca2+ by a spray method. When a chelating buffer was applied, alginate gel microdroplets were digested according to the difference in chelating efficiency of linkage-divalent cations; hence, two types of alginate microdroplets were formed. Moreover, we examined the capability of the alginate gel to exchange linkage-divalent cations and found that both Ca2+ exchange in Ba-alginate microdroplets and Ba2+ exchange in Ca-alginate microdroplets occurred. These results indicate that the potential applications of a mixture of alginate microdroplets with different divalent cations control the selective digestion of microdroplets to improve the high-throughput, high-content microdroplet-based separation, analysis, or storage of single cells.

Mapping of a quantitative trait locus for resistance against infectious salmon anaemia in Atlantic salmon (Salmo Salar): comparing survival analysis with analysis on affected/resistant data

PubMed Central

Moen, Thomas; Sonesson, Anna K; Hayes, Ben; Lien, Sigbjørn; Munck, Hege; Meuwissen, Theo HE

2007-01-01

Background Infectious Salmon Anaemia (ISA) is a viral disease affecting farmed Atlantic salmon (Salmo salar) worldwide. The identification of Quantitative Trait Loci (QTL) affecting resistance to the disease could improve our understanding of the genetics underlying the trait and provide a means for Marker-Assisted Selection. We previously performed a genome scan on commercial Atlantic salmon families challenge tested for ISA resistance, identifying several putative QTL. In the present study, we set out to validate the strongest of these QTL in a larger family material coming from the same challenge test, and to determine the position of the QTL by interval mapping. We also wanted to explore different ways of performing QTL analysis within a survival analysis framework (i.e. using time-to-event data), and to compare results using survival analysis with results from analysis on the dichotomous trait 'affected/resistant'. Results The QTL, located on Atlantic salmon linkage group 8 (following SALMAP notation), was confirmed in the new data set. Its most likely position was at a marker cluster containing markers BHMS130, BHMS170 and BHMS553. Significant segregation distortion was observed in the same region, but was shown to be unrelated to the QTL. A maximum likelihood procedure for identifying QTL, based on the Cox proportional hazard model, was developed. QTL mapping was also done using the Haley-Knott method (affected/resistant data), and within a variance-component framework (affected/resistant data and time-to-event data). In all cases, analysis using affected/resistant data gave stronger evidence for a QTL than did analysis using time-to-event data. Conclusion A QTL for resistance to Infectious Salmon Anaemia in Atlantic salmon was validated in this study, and its more precise location on linkage group eight was determined. The QTL explained 6% of the phenotypic variation in resistance to the disease. The linkage group also displayed significant segregation distortion. Survival models proved in this case not to be more suitable than models based on the dichotomous trait 'affected/resistant' for analysing the data. PMID:17697344

Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.

PubMed

Malhotra, Alka; Igo, Robert P; Thameem, Farook; Kao, W H Linda; Abboud, Hanna E; Adler, Sharon G; Arar, Nedal H; Bowden, Donald W; Duggirala, Ravindranath; Freedman, Barry I; Goddard, Katrina A B; Ipp, Eli; Iyengar, Sudha K; Kimmel, Paul L; Knowler, William C; Kohn, Orly; Leehey, David; Meoni, Lucy A; Nelson, Robert G; Nicholas, Susanne B; Parekh, Rulan S; Rich, Stephen S; Chen, Yii-Der I; Saad, Mohammed F; Scavini, Marina; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Taylor, Kent D; Thornley-Brown, Denyse; Zager, Philip G; Horvath, Amanda; Hanson, Robert L

2009-11-01

Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies. The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

Genome scan for linkage to asthma using a linkage disequilibrium-lod score test.

PubMed

Jiang, Y; Slager, S L; Huang, J

2001-01-01

We report a genome-wide linkage study of asthma on the German and Collaborative Study on the Genetics of Asthma (CSGA) data. Using a combined linkage and linkage disequilibrium test and the nonparametric linkage score, we identified 13 markers from the German data, 1 marker from the African American (CSGA) data, and 7 markers from the Caucasian (CSGA) data in which the p-values ranged between 0.0001 and 0.0100. From our analysis and taking into account previous published linkage studies of asthma, we suggest that three regions in chromosome 5 (around D5S418, D5S644, and D5S422), one region in chromosome 6 (around three neighboring markers D6S1281, D6S291, and D6S1019), one region in chromosome 11 (around D11S2362), and two regions in chromosome 12 (around D12S351 and D12S324) especially merit further investigation.

Genetic Alterations in Familial Breast Cancer: Mapping and Cloning Genes Other Than BRCAl

DTIC Science & Technology

1997-09-01

predisposition to breast cancer in families. The gene PTEN was successfully cloned by this project, and simultaneously by others (for a different ...with germline translocations’and breast cancer for the identification of tumor suppressor genes. 14. SUBJECT TERMS Breast cancer 17. SECURITY...would limit the statistical power of linkage analysis. Therefore, we decided to integrate linkage analysis with the analysis of germline chromosomal

Screening for Multiple Genes Influencing Dyslexia.

ERIC Educational Resources Information Center

Smith, Shelley D.; And Others

1991-01-01

Examines the "sib pair" method of linkage analysis designed to locate genes influencing dyslexia, which has several advantages over the "LOD" score method. Notes that the sib pair analysis was able to detect the same linkages as the LOD method, plus a possible third region. Confirms that the sib pair method is an effective means of screening. (RS)

Selective DNA Pooling for Determination of Linkage between a Molecular Marker and a Quantitative Trait Locus

PubMed Central

Darvasi, A.; Soller, M.

1994-01-01

Selective genotyping is a method to reduce costs in marker-quantitative trait locus (QTL) linkage determination by genotyping only those individuals with extreme, and hence most informative, quantitative trait values. The DNA pooling strategy (termed: ``selective DNA pooling'') takes this one step further by pooling DNA from the selected individuals at each of the two phenotypic extremes, and basing the test for linkage on marker allele frequencies as estimated from the pooled samples only. This can reduce genotyping costs of marker-QTL linkage determination by up to two orders of magnitude. Theoretical analysis of selective DNA pooling shows that for experiments involving backcross, F(2) and half-sib designs, the power of selective DNA pooling for detecting genes with large effect, can be the same as that obtained by individual selective genotyping. Power for detecting genes with small effect, however, was found to decrease strongly with increase in the technical error of estimating allele frequencies in the pooled samples. The effect of technical error, however, can be markedly reduced by replication of technical procedures. It is also shown that a proportion selected of 0.1 at each tail will be appropriate for a wide range of experimental conditions. PMID:7896115

A Genetic Linkage Map of the Hermaphrodite Teleost Fish Sparus aurata L.

PubMed Central

Franch, Rafaella; Louro, Bruno; Tsalavouta, Matina; Chatziplis, Dimitris; Tsigenopoulos, Costas S.; Sarropoulou, Elena; Antonello, Jenny; Magoulas, Andonis; Mylonas, Constantinos C.; Babbucci, Massimiliano; Patarnello, Tomaso; Power, Deborah M.; Kotoulas, Giorgos; Bargelloni, Luca

2006-01-01

The gilthead sea bream (Sparus aurata L.) is a marine fish of great importance for fisheries and aquaculture. It has also a peculiar sex-determination system, being a protandrous hermaphrodite. Here we report the construction of a first-generation genetic linkage map for S. aurata, based on 204 microsatellite markers. Twenty-six linkage groups (LG) were found. The total map length was 1241.9 cM. The ratio between sex-specific map lengths was 1:1.2 (male:female). Comparison with a preliminary radiation hybrid (RH) map reveals a good concordance, as all markers located in a single LG are located in a single RH group, except for Ad-25 and CId-31. Comparison with the Tetraodon nigroviridis genome revealed a considerable number of evolutionary conserved regions (ECRs) between the two species. The mean size of ECRs was 182 bp (sequence identity 60–90%). Forty-one ECRs have a known chromosomal location in the pufferfish genome. Despite the limited number of anchoring points, significant syntenic relationships were found. The linkage map presented here provides a robust comparative framework for QTL analysis in S. aurata and is a step toward the identification of genetic loci involved both in the determination of economically important traits and in the individual timing of sex reversal. PMID:16951080

[Analysis of HLA haplotype frequency and linkage disequilibrium in patients with acute lymphoblastic leukemia from Northern Chinese Han].

PubMed

Gao, Su-qing; Cheng, Liang-hong; Lu, Liang; Jing, Shi-zheng; Cheng, Xi; Zhang, Yin-ze; Zou, Hong-yan; Deng, Zhi-hui

2009-02-01

To analyze the difference between the frequencies of HLA-A-B, B-DRB1 and A-B-DRB1 haplotype, as well as their linkage disequilibrium pattern in patients with acute lymphoblastic leukemia(ALL) and healthy controls from Northern Chinese Han. The frequencies of HLA-A-B, B-DRB1, A-B-DR haplotypes and linkage disequilibrium were estimated by Expectation Maximization method based on the genotypes of 643 patients with ALL and 2 0359 unrelated healthy donors, and the statistical significance between the two groups were estimated by chi-square test. Linkage disequilibrium was analyzed with population genetic methods. The most common HLA-A-B, B-DRB1, and A-B-DR haplotypes were A30-B13, A2-B46, A33-B58, B13-DR7, B46-DR9, B52-DR15, B58-DR17, A30-B13-DR7, A33-B58-DR17 and A1-B37-DR10 in both groups. The frequencies of A30-B13, A2-B46, A33-B44, B13-DR7, A30-B13-DR7 and A2-B46-DR9 haplotypes and linkage disequilibrium value were significantly decreased (P<0.05) in the patient group than that in the control group. On the other hand, the frequencies of A2-B52, A31-B61, A24- B8, B60-DR9, B27-DR4, B52-DR14, B44-DR17, B27-DR12 and A11-B27-DR12 haplotypes and linkage disequilibrium value were significantly increased (P<0.05) in the patient group than that in the control group. There are some common and positive linkage disequilibrium haplotypes in both the ALL patients and the healthy donors in Northern Chinese Han. Interestingly, some haplotypes and their linkage disequilibrium patterns had significantly different distributions between the two groups. The study provided basic data for the relationship of ALL and HLA haplotype and for finding the HLA-A, B, DR matching donors.

Germplasm-regression-combined (GRC) marker-trait association identification in plant breeding: a challenge for plant biotechnological breeding under soil water deficit conditions.

PubMed

Ruan, Cheng-Jiang; Xu, Xue-Xuan; Shao, Hong-Bo; Jaleel, Cheruth Abdul

2010-09-01

In the past 20 years, the major effort in plant breeding has changed from quantitative to molecular genetics with emphasis on quantitative trait loci (QTL) identification and marker assisted selection (MAS). However, results have been modest. This has been due to several factors including absence of tight linkage QTL, non-availability of mapping populations, and substantial time needed to develop such populations. To overcome these limitations, and as an alternative to planned populations, molecular marker-trait associations have been identified by the combination between germplasm and the regression technique. In the present preview, the authors (1) survey the successful applications of germplasm-regression-combined (GRC) molecular marker-trait association identification in plants; (2) describe how to do the GRC analysis and its differences from mapping QTL based on a linkage map reconstructed from the planned populations; (3) consider the factors that affect the GRC association identification, including selections of optimal germplasm and molecular markers and testing of identification efficiency of markers associated with traits; and (4) finally discuss the future prospects of GRC marker-trait association analysis used in plant MAS/QTL breeding programs, especially in long-juvenile woody plants when no other genetic information such as linkage maps and QTL are available.

Individual Data Linkage of Survey Data with Claims Data in Germany—An Overview Based on a Cohort Study

PubMed Central

March, Stefanie

2017-01-01

Research based on health insurance data has a long tradition in Germany. By contrast, data linkage of survey data with such claims data is a relatively new field of research with high potential. Data linkage opens up new opportunities for analyses in the field of health services research and public health. Germany has comprehensive rules and regulations of data protection that have to be followed. Therefore, a written informed consent is needed for individual data linkage. Additionally, the health system is characterized by heterogeneity of health insurance. The lidA-living at work-study is a cohort study on work, age and health, which linked survey data with claims data of a large number of statutory health insurance data. All health insurance funds were contacted, of whom a written consent was given. This paper will give an overview of individual data linkage of survey data with German claims data on the example of the lidA-study results. The challenges and limitations of data linkage will be presented. Despite heterogeneity, such kind of studies is possible with a negligibly small influence of bias. The experience we gain in lidA will be shown and provide important insights for other studies focusing on data linkage. PMID:29232834

Individual Data Linkage of Survey Data with Claims Data in Germany-An Overview Based on a Cohort Study.

PubMed

March, Stefanie

2017-12-09

Research based on health insurance data has a long tradition in Germany. By contrast, data linkage of survey data with such claims data is a relatively new field of research with high potential. Data linkage opens up new opportunities for analyses in the field of health services research and public health. Germany has comprehensive rules and regulations of data protection that have to be followed. Therefore, a written informed consent is needed for individual data linkage. Additionally, the health system is characterized by heterogeneity of health insurance. The lidA-living at work-study is a cohort study on work, age and health, which linked survey data with claims data of a large number of statutory health insurance data. All health insurance funds were contacted, of whom a written consent was given. This paper will give an overview of individual data linkage of survey data with German claims data on the example of the lidA-study results. The challenges and limitations of data linkage will be presented. Despite heterogeneity, such kind of studies is possible with a negligibly small influence of bias. The experience we gain in lidA will be shown and provide important insights for other studies focusing on data linkage.

Keep your opponents close: social context affects EEG and fEMG linkage in a turn-based computer game.

PubMed

Spapé, Michiel M; Kivikangas, J Matias; Järvelä, Simo; Kosunen, Ilkka; Jacucci, Giulio; Ravaja, Niklas

2013-01-01

In daily life, we often copy the gestures and expressions of those we communicate with, but recent evidence shows that such mimicry has a physiological counterpart: interaction elicits linkage, which is a concordance between the biological signals of those involved. To find out how the type of social interaction affects linkage, pairs of participants played a turn-based computer game in which the level of competition was systematically varied between cooperation and competition. Linkage in the beta and gamma frequency bands was observed in the EEG, especially when the participants played directly against each other. Emotional expression, measured using facial EMG, reflected this pattern, with the most competitive condition showing enhanced linkage over the facial muscle-regions involved in smiling. These effects were found to be related to self-reported social presence: linkage in positive emotional expression was associated with self-reported shared negative feelings. The observed effects confirmed the hypothesis that the social context affected the degree to which participants had similar reactions to their environment and consequently showed similar patterns of brain activity. We discuss the functional resemblance between linkage, as an indicator of a shared physiology and affect, and the well-known mirror neuron system, and how they relate to social functions like empathy.

A procedure for linking psychosocial job characteristics data to health surveys.

PubMed Central

Schwartz, J E; Pieper, C F; Karasek, R A

1988-01-01

A system is presented for linking information about psychosocial characteristics of job situations to national health surveys. Job information can be imputed to individuals on surveys that contain three-digit US Census occupation codes. Occupational mean scores on psychosocial job characteristics-control over task situation (decision latitude), psychological work load, physical exertion, and other measures-for the linkage system are derived from US national surveys of working conditions (Quality of Employment Surveys 1969, 1972, and 1977). This paper discusses a new method for reducing the biases in multivariate analyses that are likely to arise when utilizing linkage systems based on mean scores. Such biases are reduced by modifying the linkage system to adjust imputed individual scores for demographic factors such as age, education, race, marital status and, implicitly, sex (since men and women have separate linkage data bases). Statistics on the linkage system's efficiency and reliability are reported. All dimensions have high inter-survey reproducibility. Despite their psychosocial nature, decision latitude and physical exertion can be more efficiently imputed with the linkage system than earnings (a non-psychosocial job characteristic). The linkage system presented here is a useful tool for initial epidemiological studies of the consequences of psychosocial job characteristics and constitutes the methodological basis for the subsequent paper. PMID:3389426

Ultra-high density intra-specific genetic linkage maps accelerate identification of functionally relevant molecular tags governing important agronomic traits in chickpea

PubMed Central

Kujur, Alice; Upadhyaya, Hari D.; Shree, Tanima; Bajaj, Deepak; Das, Shouvik; Saxena, Maneesha S.; Badoni, Saurabh; Kumar, Vinod; Tripathi, Shailesh; Gowda, C. L. L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

2015-01-01

We discovered 26785 and 16573 high-quality SNPs differentiating two parental genotypes of a RIL mapping population using reference desi and kabuli genome-based GBS assay. Of these, 3625 and 2177 SNPs have been integrated into eight desi and kabuli chromosomes, respectively in order to construct ultra-high density (0.20–0.37 cM) intra-specific chickpea genetic linkage maps. One of these constructed high-resolution genetic map has potential to identify 33 major genomic regions harbouring 35 robust QTLs (PVE: 17.9–39.7%) associated with three agronomic traits, which were mapped within <1 cM mean marker intervals on desi chromosomes. The extended LD (linkage disequilibrium) decay (~15 cM) in chromosomes of genetic maps have encouraged us to use a rapid integrated approach (comparative QTL mapping, QTL-region specific haplotype/LD-based trait association analysis, expression profiling and gene haplotype-based association mapping) rather than a traditional QTL map-based cloning method to narrow-down one major seed weight (SW) robust QTL region. It delineated favourable natural allelic variants and superior haplotype-containing one seed-specific candidate embryo defective gene regulating SW in chickpea. The ultra-high-resolution genetic maps, QTLs/genes and alleles/haplotypes-related genomic information generated and integrated strategy for rapid QTL/gene identification developed have potential to expedite genomics-assisted breeding applications in crop plants, including chickpea for their genetic enhancement. PMID:25942004

Computer Simulation Is an Undervalued Tool for Genetic Analysis: A Historical View and Presentation of SHIMSHON – A Web-Based Genetic Simulation Package

PubMed Central

Greenberg, David A.

2011-01-01

Computer simulation methods are under-used tools in genetic analysis because simulation approaches have been portrayed as inferior to analytic methods. Even when simulation is used, its advantages are not fully exploited. Here, I present SHIMSHON, our package of genetic simulation programs that have been developed, tested, used for research, and used to generated data for Genetic Analysis Workshops (GAW). These simulation programs, now web-accessible, can be used by anyone to answer questions about designing and analyzing genetic disease studies for locus identification. This work has three foci: (1) the historical context of SHIMSHON's development, suggesting why simulation has not been more widely used so far. (2) Advantages of simulation: computer simulation helps us to understand how genetic analysis methods work. It has advantages for understanding disease inheritance and methods for gene searches. Furthermore, simulation methods can be used to answer fundamental questions that either cannot be answered by analytical approaches or cannot even be defined until the problems are identified and studied, using simulation. (3) I argue that, because simulation was not accepted, there was a failure to grasp the meaning of some simulation-based studies of linkage. This may have contributed to perceived weaknesses in linkage analysis; weaknesses that did not, in fact, exist. PMID:22189467

Linkages between Total Quality Management and the Outcomes-Based Approach in an Education Environment

ERIC Educational Resources Information Center

de Jager, H. J.; Nieuwenhuis, F. J.

2005-01-01

South Africa has embarked on a process of education renewal by adopting outcomes-based education (OBE). This paper focuses on the linkages between total quality management (TQM) and the outcomes-based approach in an education context. Quality assurance in academic programmes in higher education in South Africa is, in some instances, based on the…

Haptic device for telerobotic surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salisbury, Curt; Salisbury, Jr., J. Kenneth

A haptic device for telerobotic surgery, including a base; a linkage system having first and second linkage members coupled to the base; a motor that provides a motor force; a transmission including first and second driving pulleys arranged such that their faces form an angle and their axes form a plane, first and second idler pulleys offset from the plane and arranged between the first and second driving pulleys such that their axes divide the angle between the first and second driving pulleys, and a cable that traverses the first and second driving pulleys and the set of idler pulleysmore » and transfers the motor force to the linkage system; an end effector coupled to distal ends of the first and second linkage members and maneuverable relative to the base; and a controller that modulates the motor force to simulate a body part at a point portion of the end effector.« less

Research-Practice Linkages in Extension Leadership Development Programs: Focus on Community Leadership Development Programs. A Report.

ERIC Educational Resources Information Center

Vandenberg, Lela; And Others

The Research-Practice Linkages Project sought to identify the knowledge base supporting community leadership development (CLD) programs of the Cooperative Extension Service and to determine linkages between Extension programs and CLD research. A mail questionnaire was completed by 492 Extension staff involved in CLD programs in 18 states and 42…

Richness-Productivity Relationships Between Trophic Levels in a Detritus-Based System: Significance of Abundance and Trophic Linkage.

EPA Science Inventory

Most theoretical and empirical studies of productivity–species richness relationships fail to consider linkages among trophic levels. We quantified productivity–richness relationships in detritus-based, water-filled tree-hole communities for two trophic levels: invertebrate consu...

Assigning Peptide Disulfide Linkage Pattern Among Regio-Isomers via Methoxy Addition to Disulfide and Tandem Mass Spectrometry

NASA Astrophysics Data System (ADS)

Durand, Kirt L.; Tan, Lei; Stinson, Craig A.; Love-Nkansah, Chasity B.; Ma, Xiaoxiao; Xia, Yu

2017-06-01

Pinpointing disulfide linkage pattern is critical in the characterization of proteins and peptides consisting of multiple disulfide bonds. Herein, we report a method based on coupling online disulfide modification and tandem mass spectrometry (MS/MS) to distinguish peptide disulfide regio-isomers. Such a method relies on a new disulfide bond cleavage reaction in solution, involving methanol as a reactant and 254 nm ultraviolet (UV) irradiation. This reaction leads to selective cleavage of a disulfide bond and formation of sulfenic methyl ester (-SOCH3) at one cysteine residue and a thiol (-SH) at the other. Under low energy collision-induced dissociation (CID), cysteine sulfenic methyl ester motif produces a signature methanol loss (-32 Da), allowing its identification from other possible isomeric structures such as S-hydroxylmethyl (-SCH2OH) and methyl sulfoxide (-S(O)-CH3). Since disulfide bond can be selectively cleaved and modified upon methoxy addition, subsequent MS2 CID of the methoxy addition product provides enhanced sequence coverage as demonstrated by the analysis of bovine insulin. More importantly, this reaction does not induce disulfide scrambling, likely due to the fact that radical intermediates are not involved in the process. An approach based on methoxy addition followed by MS3 CID has been developed for assigning disulfide linkage patterns in peptide disulfide regio-isomers. This methodology was successfully applied to characterizing peptide systems having two disulfide bonds and three disulfide linkage isomers: side-by-side, overlapped, and looped-within-a-loop configurations. [Figure not available: see fulltext.

Reductions in Hard Drug Use Among Homeless Youth Receiving a Strength-Based Outreach Intervention: Comparing the Long-Term Effects of Shelter Linkage Versus Drop-in Center Linkage.

PubMed

Guo, Xiamei; Slesnick, Natasha

2017-06-07

The current study sought to test hard drug use outcomes for youth receiving a strengths-based outreach and advocacy intervention that linked youth to either a shelter or a drop-in center. Homeless youth (14-24 years old) were engaged by research assistants (RAs) at soup kitchens, parks, libraries, and other locations that homeless youth were known to frequent. Youth were randomly assigned to receive six months of advocacy that focused on linking youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). Follow-up assessments were conducted at 3, 6, and 9 months post-baseline. Hard drug use over time was the main outcome. Intervention condition and service connection were used as predictors for the baseline level and the slope of change in hard drug use over time. Data analysis was conducted with Bernoulli Hierarchical Generalized Linear Modeling in HLM7. The current study found that those who were in the drop-in linkage condition exhibited a greater reduction in their odds of using hard drugs during the follow-up points than their counterparts in the shelter linkage condition. And finally, those who utilized services more often during the follow-ups were those who exhibited less hard drug use at baseline and less reduction in their odds of using hard drugs. This study suggests that drop-in centers, which are often characterized by low-demand programming and few behavioral restrictions, are effective for addressing hard drug use among homeless youth.

Dynamic analysis of six-bar mechanical press for deep drawing

NASA Astrophysics Data System (ADS)

Mitsi, S.; Tsiafis, I.; Bouzakis, K. D.

2017-02-01

This paper analyzes the dynamical behavior of a six-bar linkage used in mechanical presses for metal forming such as deep drawing. In the under study mechanism, a four-bar linkage is connected to a slider through an articulated binary link. The motion of the six-bar linkage is studied by kinematic analysis developing an analytical method. Furthermore, using an iterative method and d’ Alembert’s principle, the joint forces and drive moment are evaluated considering joint frictions. The simulation results obtained with a MATLAB program are validated by comparing the theoretical values of the input moment with the ones obtained from the conservation of energy law.

Barriers Influencing Linkage to Hypertension Care in Kenya: Qualitative Analysis from the LARK Hypertension Study.

PubMed

Naanyu, Violet; Vedanthan, Rajesh; Kamano, Jemima H; Rotich, Jackson K; Lagat, Kennedy K; Kiptoo, Peninah; Kofler, Claire; Mutai, Kennedy K; Bloomfield, Gerald S; Menya, Diana; Kimaiyo, Sylvester; Fuster, Valentin; Horowitz, Carol R; Inui, Thomas S

2016-03-01

Hypertension, the leading global risk factor for mortality, is characterized by low treatment and control rates in low- and middle-income countries. Poor linkage to hypertension care contributes to poor outcomes for patients. However, specific factors influencing linkage to hypertension care are not well known. To evaluate factors influencing linkage to hypertension care in rural western Kenya. Qualitative research study using a modified Health Belief Model that incorporates the impact of emotional and environmental factors on behavior. Mabaraza (traditional community assembly) participants (n = 242) responded to an open invitation to residents in their respective communities. Focus groups, formed by purposive sampling, consisted of hypertensive individuals, at-large community members, and community health workers (n = 169). We performed content analysis of the transcripts with NVivo 10 software, using both deductive and inductive codes. We used a two-round Delphi method to rank the barriers identified in the content analysis. We selected factors using triangulation of frequency of codes and themes from the transcripts, in addition to the results of the Delphi exercise. Sociodemographic characteristics of participants were summarized using descriptive statistics. We identified 27 barriers to linkage to hypertension care, grouped into individual (cognitive and emotional) and environmental factors. Cognitive factors included the asymptomatic nature of hypertension and limited information. Emotional factors included fear of being a burden to the family and fear of being screened for stigmatized diseases such as HIV. Environmental factors were divided into physical (e.g. distance), socioeconomic (e.g. poverty), and health system factors (e.g. popularity of alternative therapies). The Delphi results were generally consistent with the findings from the content analysis. Individual and environmental factors are barriers to linkage to hypertension care in rural western Kenya. Our analysis provides new insights and methodological approaches that may be relevant to other low-resource settings worldwide.

Development of microsatellite markers from an enriched genomic library for genetic analysis of melon (Cucumis melo L.)

PubMed Central

Ritschel, Patricia Silva; Lins, Tulio Cesar de Lima; Tristan, Rodrigo Lourenço; Buso, Gláucia Salles Cortopassi; Buso, José Amauri; Ferreira, Márcio Elias

2004-01-01

Background Despite the great advances in genomic technology observed in several crop species, the availability of molecular tools such as microsatellite markers has been limited in melon (Cucumis melo L.) and cucurbit species. The development of microsatellite markers will have a major impact on genetic analysis and breeding of melon, especially on the generation of marker saturated genetic maps and implementation of marker assisted breeding programs. Genomic microsatellite enriched libraries can be an efficient alternative for marker development in such species. Results Seven hundred clones containing microsatellite sequences from a Tsp-AG/TC microsatellite enriched library were identified and one-hundred and forty-four primer pairs designed and synthesized. When 67 microsatellite markers were tested on a panel of melon and other cucurbit accessions, 65 revealed DNA polymorphisms among the melon accessions. For some cucurbit species, such as Cucumis sativus, up to 50% of the melon microsatellite markers could be readily used for DNA polymophism assessment, representing a significant reduction of marker development costs. A random sample of 25 microsatellite markers was extracted from the new microsatellite marker set and characterized on 40 accessions of melon, generating an allelic frequency database for the species. The average expected heterozygosity was 0.52, varying from 0.45 to 0.70, indicating that a small set of selected markers should be sufficient to solve questions regarding genotype identity and variety protection. Genetic distances based on microsatellite polymorphism were congruent with data obtained from RAPD marker analysis. Mapping analysis was initiated with 55 newly developed markers and most primers showed segregation according to Mendelian expectations. Linkage analysis detected linkage between 56% of the markers, distributed in nine linkage groups. Conclusions Genomic library microsatellite enrichment is an efficient procedure for marker development in melon. One-hundred and forty-four new markers were developed from Tsp-AG/TC genomic library. This is the first reported attempt of successfully using enriched library for microsatellite marker development in the species. A sample of the microsatellite markers tested proved efficient for genetic analysis of melon, including genetic distance estimates and identity tests. Linkage analysis indicated that the markers developed are dispersed throughout the genome and should be very useful for genetic analysis of melon. PMID:15149552

Hereditary spastic paraplegia: LOD-score considerations for confirmation of linkage in a heterogeneous trait.

PubMed

Dubé, M P; Mlodzienski, M A; Kibar, Z; Farlow, M R; Ebers, G; Harper, P; Kolodny, E H; Rouleau, G A; Figlewicz, D A

1997-03-01

Hereditary spastic paraplegia (HSP) is a degenerative disorder of the motor system, defined by progressive weakness and spasticity of the lower limbs. HSP may be inherited as an autosomal dominant (AD), autosomal recessive, or an X-linked trait. AD HSP is genetically heterogeneous, and three loci have been identified so far: SPG3 maps to chromosome 14q, SPG4 to 2p, and SPG4a to 15q. We have undertaken linkage analysis with 21 uncomplicated AD families to the three AD HSP loci. We report significant linkage for three of our families to the SPG4 locus and exclude several families by multipoint linkage. We used linkage information from several different research teams to evaluate the statistical probability of linkage to the SPG4 locus for uncomplicated AD HSP families and established the critical LOD-score value necessary for confirmation of linkage to the SPG4 locus from Bayesian statistics. In addition, we calculated the empirical P-values for the LOD scores obtained with all families with computer simulation methods. Power to detect significant linkage, as well as type I error probabilities, were evaluated. This combined analytical approach permitted conclusive linkage analyses on small to medium-size families, under the restrictions of genetic heterogeneity.

Localization of a gene responsible for nonspecific mental retardation (MRX9) to the pericentromeric region of the X chromosome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willems, P.; Vits, L.; Buntinx, I.

1993-11-01

Nonspecific X-linked mental retardation (MRX) includes several distinct entities with mental retardation but without additional distinguishing features. The MRX family reported here has been classified previously as MRX9. In this study, the authors performed linkage analysis of MRX9 with a panel of 43 polymorphic DNA markers dispersed over chromosome X. Two-point linkage analysis revealed lod scores of 3.52 and 3.82 at 0% recombination for OATL1 and MAOA, both located in Xp11.2-p11.4. Lod scores for linkage with PGK1P1, DXS106, and DXS132, all located in Xq11-q13, were 3.83, 3.82, and 3.52, respectively, all at 0% recombination. Multipoint linkage analysis showed two peaksmore » with MAOA and DXS132/DXS106, respectively. Analysis of recombinational events indicated a position of the MRX9 gene between DXS164 and DXS453. These findings are compatible with a location of the MRX9 gene in the pericentromeric region of the X chromosome at Xp21-q13. 26 refs., 3 figs., 2 tabs.« less

Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q.

PubMed

Holmans, Peter; Zubenko, George S; Crowe, Raymond R; DePaulo, J Raymond; Scheftner, William A; Weissman, Myrna M; Zubenko, Wendy N; Boutelle, Sandra; Murphy-Eberenz, Kathleen; MacKinnon, Dean; McInnis, Melvin G; Marta, Diana H; Adams, Philip; Knowles, James A; Gladis, Madeleine; Thomas, Jo; Chellis, Jennifer; Miller, Erin; Levinson, Douglas F

2004-06-01

A genome scan was performed on the first phase sample of the Genetics of Recurrent Early-Onset Depression (GenRED) project. The sample consisted of 297 informative families containing 415 independent affected sibling pairs (ASPs), or, counting all possible pairs, 685 informative affected relative pairs (555 ASPs and 130 other pair types). Affected cases had recurrent major depressive disorder (MDD) with onset before age 31 years for probands or age 41 years for other affected relatives; the mean age at onset was 18.5 years, and the mean number of depressive episodes was 7.3. The Center for Inherited Disease Research genotyped 389 microsatellite markers (mean spacing of 9.3 cM). The primary linkage analysis considered allele sharing in all possible affected relative pairs with the use of the Z(lr) statistic computed by the ALLEGRO program. A secondary logistic regression analysis considered the effect of the sex of the pair as a covariate. Genomewide significant linkage was observed on chromosome 15q25.3-26.2 (Zlr=4.14, equivalent LOD = 3.73, empirical genomewide P=.023). The linkage was not sex specific. No other suggestive or significant results were observed in the primary analysis. The secondary analysis produced three regions of suggestive linkage, but these results should be interpreted cautiously because they depended primarily on the small subsample of 42 male-male pairs. Chromosome 15q25.3-26.2 deserves further study as a candidate region for susceptibility to MDD.

[Linkage analysis of a family with familial hypertriglyceridemia].

PubMed

Tang, Xin; Lin, Ying; Liu, Bing; Ma, Shi; Yang, Yang; Yang, Zheng-lin

2009-10-01

To perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG). Thirty-two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing. No linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB, CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (theta =0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at theta =0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes. The above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.

Quantitative trait locus mapping under irrigated and drought treatments based on a novel genetic linkage map in mungbean (Vigna radiata L.).

PubMed

Liu, Changyou; Wu, Jing; Wang, Lanfen; Fan, Baojie; Cao, Zhimin; Su, Qiuzhu; Zhang, Zhixiao; Wang, Yan; Tian, Jing; Wang, Shumin

2017-11-01

A novel genetic linkage map was constructed using SSR markers and stable QTLs were identified for six drought tolerance related-traits using single-environment analysis under irrigation and drought treatments. Mungbean (Vigna radiata L.) is one of the most important leguminous food crops. However, mungbean production is seriously constrained by drought. Isolation of drought-responsive genetic elements and marker-assisted selection breeding will benefit from the detection of quantitative trait locus (QTLs) for traits related to drought tolerance. In this study, we developed a full-coverage genetic linkage map based on simple sequence repeat (SSR) markers using a recombinant inbred line (RIL) population derived from an intra-specific cross between two drought-resistant varieties. This novel map was anchored with 313 markers. The total map length was 1010.18 cM across 11 linkage groups, covering the entire genome of mungbean with a saturation of one marker every 3.23 cM. We subsequently detected 58 QTLs for plant height (PH), maximum leaf area (MLA), biomass (BM), relative water content, days to first flowering, and seed yield (Yield) and 5 for the drought tolerance index of 3 traits in irrigated and drought environments at 2 locations. Thirty-eight of these QTLs were consistently detected two or more times at similar linkage positions. Notably, qPH5A and qMLA2A were consistently identified in marker intervals from GMES5773 to MUS128 in LG05 and from Mchr11-34 to the HAAS_VR_1812 region in LG02 in four environments, contributing 6.40-20.06% and 6.97-7.94% of the observed phenotypic variation, respectively. None of these QTLs shared loci with previously identified drought-related loci from mungbean. The results of these analyses might facilitate the isolation of drought-related genes and help to clarify the mechanism of drought tolerance in mungbean.

Cost analysis of two community-based HIV testing service modalities led by a Non-Governmental Organization in Cape Town, South Africa.

PubMed

Meehan, Sue-Ann; Beyers, Nulda; Burger, Ronelle

2017-12-02

In South Africa, the financing and sustainability of HIV services is a priority. Community-based HIV testing services (CB-HTS) play a vital role in diagnosis and linkage to HIV care for those least likely to utilise government health services. With insufficient estimates of the costs associated with CB-HTS provided by NGOs in South Africa, this cost analysis explored the cost to implement and provide services at two NGO-led CB-HTS modalities and calculated the costs associated with realizing key HIV outputs for each CB-HTS modality. The study took place in a peri-urban area where CB-HTS were provided from a stand-alone centre and mobile service. Using a service provider (NGO) perspective, all inputs were allocated by HTS modality with shared costs apportioned according to client volume or personnel time. We calculated the total cost of each HTS modality and the cost categories (personnel, capital and recurring goods/services) across each HTS modality. Costs were divided into seven pre-determined project components, used to examine cost drivers. HIV outputs were analysed for each HTS modality and the mean cost for each HIV output was calculated per HTS modality. The annual cost of the stand-alone and mobile modalities was $96,616 and $77,764 respectively, with personnel costs accounting for 54% of the total costs at the stand-alone. For project components, overheads and service provision made up the majority of the costs. The mean cost per person tested at stand-alone ($51) was higher than at the mobile ($25). Linkage to care cost at the stand-alone ($1039) was lower than the mobile ($2102). This study provides insight into the cost of an NGO led CB-HTS project providing HIV testing and linkage to care through two CB-HIV testing modalities. The study highlights; (1) the importance of including all applicable costs (including overheads) to ensure an accurate cost estimate that is representative of the full service implementation cost, (2) the direct link between test uptake and mean cost per person tested, and (3) the need for effective linkage to care strategies to increase linkage and thereby reduce the mean cost per person linked to HIV care.

Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits

PubMed Central

Hinckley, Jesse D; Abbott, Diana; Burns, Trudy L; Heiman, Meadow; Shapiro, Amy D; Wang, Kai; Di Paola, Jorge

2013-01-01

We characterized a large Amish pedigree and, in 384 pedigree members, analyzed the genetic variance components with covariate screen as well as genome-wide quantitative trait locus (QTL) linkage analysis of red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count (PLT), and white blood cell count (WBC) using SOLAR. Age and gender were found to be significant covariates in many CBC traits. We obtained significant heritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC. We report four candidate loci with Logarithm of the odds (LOD) scores above 2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We also report eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariate linkage analysis of MCV and MCH on chromosome 20 resulted in a higher maximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22, 6q25, and 20q13 are concomitant with previously reported QTL. All other linkage signals reported herein represent novel evidence of candidate QTL. Interestingly rs1800562, the most common causal variant of hereditary hemochromatosis in HFE (6p22) was associated with MCH and MCHC in this family. Linkage studies like the one presented here will allow investigators to focus the search for rare variants amidst the noise encountered in the large amounts of data generated by whole-genome sequencing. PMID:24058921

Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fain, P.R.; Barker, D.F.; Chance, P.F.

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.

Genotyping by sequencing for SNP-based linkage analysis and identification of QTLs linked to fruit quality traits in Japanese plum (Prunus salicina Lindl.)

USDA-ARS?s Scientific Manuscript database

Marker-assisted selection (MAS) in stone fruit (Prunus species) breeding is currently difficult to achieve due to the polygenic nature of themost relevant agronomic traits linked to fruit quality. Genotyping by sequencing (GBS), however, provides a large quantity of useful data suitable for finemapp...

Linkage of Bardet-Biedl syndrome to chromosome 16q and evidence for non-allelic genetic heterogeneity.

PubMed

Kwitek-Black, A E; Carmi, R; Duyk, G M; Buetow, K H; Elbedour, K; Parvari, R; Yandava, C N; Stone, E M; Sheffield, V C

1993-12-01

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by mental retardation, obesity, retinitis pigmentosa, polydactyly and hypogonadism. Other findings include hypertension, diabetes mellitus and renal and cardiovascular anomalies. We have performed a genome-wide search for linkage in a large inbred Bedouin family. Pairwise analysis established linkage with the locus D16S408 with no recombination and a lod score of 4.2. A multilocus lod score of 5.3 was observed. By demonstrating homozygosity, in all affected individuals, for the same allele of marker D16S408, further support for linkage is found, and the utility of homozygosity mapping using inbred families is demonstrated. In a second family, linkage was excluded at this locus, suggesting non-allelic genetic heterogeneity in this disorder.

Linking stressors and ecological responses

USGS Publications Warehouse

Gentile, J.H.; Solomon, K.R.; Butcher, J.B.; Harrass, M.; Landis, W.G.; Power, M.; Rattner, B.A.; Warren-Hicks, W.J.; Wenger, R.; Foran, Jeffery A.; Ferenc, Susan A.

1999-01-01

To characterize risk, it is necessary to quantify the linkages and interactions between chemical, physical and biological stressors and endpoints in the conceptual framework for ecological risk assessment (ERA). This can present challenges in a multiple stressor analysis, and it will not always be possible to develop a quantitative stressor-response profile. This review commences with a conceptual representation of the problem of developing a linkage analysis for multiple stressors and responses. The remainder of the review surveys a variety of mathematical and statistical methods (e.g., ranking methods, matrix models, multivariate dose-response for mixtures, indices, visualization, simulation modeling and decision-oriented methods) for accomplishing the linkage analysis for multiple stressors. Describing the relationships between multiple stressors and ecological effects are critical components of 'effects assessment' in the ecological risk assessment framework.

Genetic linkage analysis of schizophrenia using chromosome 11q13-24 markers in Israeli pedigrees

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mulcrone, J.; Marchblanks, R.; Whatley, S.A.

It is generally agreed that there is a genetic component in the etiology of schizophrenia which may be tested by the application of linkage analysis to multiply-affected families. One genetic region of interest is the long arm of chromosome 11 because of previously reported associations of genetic variation in this region with schizophrenia, and because of the fact that it contains the locus for the dopamine D2 receptor gene. In this study we have examined the segregation of schizophrenia with microsatellite dinucleotide repeat DNA markers along chromosome 11q in 5 Israeli families multiply-affected for schizophrenia. The hypothesis of linkage undermore » genetic homogeneity of causation was tested under a number of genetic models. Linkage analysis provided no evidence for significant causal mutations within the region bounded by INT and D11S420 on chromosome 11q. It is still possible, however, that a gene of major effect exists in this region, either with low penetrance or with heterogeneity. 32 refs., 2 figs., 4 tabs.« less

Linkage analysis in Usher syndrome type I (USH1) families from Spain.

PubMed Central

Espinós, C; Nájera, C; Millán, J M; Ayuso, C; Baiget, M; Pérez-Garrigues, H; Rodrigo, O; Vilela, C; Beneyto, M

1998-01-01

Usher syndrome (USH) is an autosomal recessive hereditary disorder characterised by congenital sensorineural hearing loss and gradual visual impairment secondary to retinitis pigmentosa (RP). The disorder is clinically and genetically heterogeneous. With regard to Usher type I (USH1), several subtypes have been described, the most frequent being USH1B located on chromosome 11q13.5. Of 18 USH1 families studied by linkage analysis, 12 (67%) showed significant lod score values for locus D11S527 (Zmax=14.032, theta=0.000) situated on chromosome 11q. Our findings suggest considerable genetic heterogeneity in the Spanish USH1 population. It is important to note that one of our families linked to the USH1B locus shows interesting intrafamilial clinical variability. As regards the remaining six USH1 families, the linkage analysis did not provide conclusive data, although two of them show slight linkage to markers located on chromosome 3q (Zmax=1.880, theta=0.000 for D3S1279), the same location that had previously been assigned to some USH3 families. Images PMID:9610802

Saturation of an intra-gene pool linkage map: toward unified consensus linkage map in common bean

USDA-ARS?s Scientific Manuscript database

Map-based cloning to find genes of interest and marker assisted selection (MAS) requires good genetic maps with high reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers in includin...

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

USDA-ARS?s Scientific Manuscript database

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...

[Linkage analysis of susceptibility loci in 2 target chromosomes in pedigrees with paranoid schizophrenia and undifferentiated schizophrenia].

PubMed

Zeng, Li-ping; Hu, Zheng-mao; Mu, Li-li; Mei, Gui-sen; Lu, Xiu-ling; Zheng, Yong-jun; Li, Pei-jian; Zhang, Ying-xue; Pan, Qian; Long, Zhi-gao; Dai, He-ping; Zhang, Zhuo-hua; Xia, Jia-hui; Zhao, Jing-ping; Xia, Kun

2011-06-01

To investigate the relationship of susceptibility loci in chromosomes 1q21-25 and 6p21-25 and schizophrenia subtypes in Chinese population. A genomic scan and parametric and non-parametric analyses were performed on 242 individuals from 36 schizophrenia pedigrees, including 19 paranoid schizophrenia and 17 undifferentiated schizophrenia pedigrees, from Henan province of China using 5 microsatellite markers in the chromosome region 1q21-25 and 8 microsatellite markers in the chromosome region 6p21-25, which were the candidates of previous studies. All affected subjects were diagnosed and typed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised (DSM-IV-TR; American Psychiatric Association, 2000). All subjects signed informed consent. In chromosome 1, parametric analysis under the dominant inheritance mode of all 36 pedigrees showed that the maximum multi-point heterogeneity Log of odds score method (HLOD) score was 1.33 (α = 0.38). The non-parametric analysis and the single point and multi-point nonparametric linkage (NPL) scores suggested linkage at D1S484, D1S2878, and D1S196. In the 19 paranoid schizophrenias pedigrees, linkage was not observed for any of the 5 markers. In the 17 undifferentiated schizophrenia pedigrees, the multi-point NPL score was 1.60 (P= 0.0367) at D1S484. The single point NPL score was 1.95(P= 0.0145) and the multi-point NPL score was 2.39 (P= 0.0041) at D1S2878. Additionally, the multi-point NPL score was 1.74 (P= 0.0255) at D1S196. These same three loci showed suggestive linkage during the integrative analysis of all 36 pedigrees. In chromosome 6, parametric linkage analysis under the dominant and recessive inheritance and the non-parametric linkage analysis of all 36 pedigrees and the 17 undifferentiated schizophrenia pedigrees, linkage was not observed for any of the 8 markers. In the 19 paranoid schizophrenias pedigrees, parametric analysis showed that under recessive inheritance mode the maximum single-point HLOD score was 1.26 (α = 0.40) and the multi-point HLOD was 1.12 (α = 0.38) at D6S289 in the chromosome 6p23. In nonparametric analysis, the single-point NPL score was 1.52 (P= 0.0402) and the multi-point NPL score was 1.92 (P= 0.0206) at D6S289. Susceptibility genes correlated with undifferentiated schizophrenia pedigrees from D1S484, D1S2878, D1S196 loci, and those correlated with paranoid schizophrenia pedigrees from D6S289 locus are likely present in chromosome regions 1q23.3 and 1q24.2, and chromosome region 6p23, respectively.

Lack of genetic linkage evidence for a trans-acting factor having a large effect on plasma lipoprotein[a] levels in African Americans.

PubMed

Barkley, Ruth Ann; Brown, Andrew C; Hanis, Craig L; Kardia, Sharon L; Turner, Stephen T; Boerwinkle, Eric

2003-07-01

The distribution of plasma lipoprotein[a] (Lp[a]) concentrations, a risk factor for cardiovascular disease, varies greatly among racial groups, with African Americans having values that are shifted toward higher levels than those of whites. The underlying cause of this heterogeneity is unknown, but a role for "trans-acting" factors has been hypothesized. This study used genetic linkage analysis to localize genetic factors influencing Lp[a] levels in African Americans that were absent in other populations; linkage results were analyzed separately in non-Hispanic whites, Hispanic whites, and African Americans. As expected, all three samples showed highly significant linkage at the approximate location of the lysophosphatidic acid locus. The white populations also independently had regions of significant linkage on chromosome 19 (LOD 3.80) and suggestive linkage on chromosomes 12 (LOD 1.60), 14 (LOD 2.56), and 19 (LOD 2.52). No linkage evidence was found to support the hypothesis of another single gene with large effects specifically segregating in African Americans that may account for their elevated Lp[a] levels.

BeetleBase in 2010: Revisions to Provide Comprehensive Genomic Information for Tribolium castaneum

USDA-ARS?s Scientific Manuscript database

BeetleBase (http://www.beetlebase.org) has been updated to provide more comprehensive genomic information for the red flour beetle Tribolium castaneum. The database contains genomic sequence scaffolds mapped to 10 linkage groups (genome assembly release Tcas_3.0), genetic linkage maps, the official ...

Validation of an instrument to measure inter-organisational linkages in general practice.

PubMed

Amoroso, Cheryl; Proudfoot, Judith; Bubner, Tanya; Jayasinghe, Upali W; Holton, Christine; Winstanley, Julie; Beilby, Justin; Harris, Mark F

2007-12-03

Linkages between general medical practices and external services are important for high quality chronic disease care. The purpose of this research is to describe the development, evaluation and use of a brief tool that measures the comprehensiveness and quality of a general practice's linkages with external providers for the management of patients with chronic disease. In this study, clinical linkages are defined as the communication, support, and referral arrangements between services for the care and assistance of patients with chronic disease. An interview to measure surgery-level (rather than individual clinician-level) clinical linkages was developed, piloted, reviewed, and evaluated with 97 Australian general practices. Two validated survey instruments were posted to patients, and a survey of locally available services was developed and posted to participating Divisions of General Practice (support organisations). Hypotheses regarding internal validity, association with local services, and patient satisfaction were tested using factor analysis, logistic regression and multilevel regression models. The resulting General Practice Clinical Linkages Interview (GP-CLI) is a nine-item tool with three underlying factors: referral and advice linkages, shared care and care planning linkages, and community access and awareness linkages. Local availability of chronic disease services has no affect on the comprehensiveness of services with which practices link, however, comprehensiveness of clinical linkages has an association with patient assessment of access, receptionist services, and of continuity of care in their general practice. The GP-CLI may be useful to researchers examining comparable health care systems for measuring the comprehensiveness and quality of linkages at a general practice-level with related services, possessing both internal and external validity. The tool can be used with large samples exploring the impact, outcomes, and facilitators of high quality clinical linkages in general practice.

Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, L.J.; Compton, J.G.; Bale, S.J.

The authors have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of themore » enzymes responsible for cross-linking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI (Z = 9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates.« less

Haplotype analysis and a novel allele-sharing method refines a chromosome 4p locus linked to bipolar affective disorder.

PubMed

Le Hellard, Stephanie; Lee, Andrew J; Underwood, Sarah; Thomson, Pippa A; Morris, Stewart W; Torrance, Helen S; Anderson, Susan M; Adams, Richard R; Navarro, Pau; Christoforou, Andrea; Houlihan, Lorna M; Detera-Wadleigh, Sevilla; Owen, Michael J; Asherson, Philip; Muir, Walter J; Blackwood, Douglas H R; Wray, Naomi R; Porteous, David J; Evans, Kathryn L

2007-03-15

Bipolar affective disorder (BPAD) and schizophrenia (SCZ) are common conditions. Their causes are unknown, but they include a substantial genetic component. Previously, we described significant linkage of BPAD to a chromosome 4p locus within a large pedigree (F22). Others subsequently have found evidence for linkage of BPAD and SCZ to this region. We constructed high-resolution haplotypes for four linked families, calculated logarithm of the odds (LOD) scores, and developed a novel method to assess the extent of allele sharing within genes between the families. We describe an increase in the F22 LOD score for this region. Definition and comparison of the linked haplotypes allowed us to prioritize two subregions of 3.8 and 4.4 Mb. Analysis of the extent of allele sharing within these subregions identified 200 kb that shows increased allele sharing between families. Linkage of BPAD to chromosome 4p has been strengthened. Haplotype analysis in the additional linked families refined the 20-Mb linkage region. Development of a novel allele-sharing method allowed us to bridge the gap between conventional linkage and association studies. Description of a 200-kb region of increased allele sharing prioritizes this region, which contains two functional candidate genes for BPAD, SLC2A9, and WDR1, for subsequent studies.

Carbohydrate intake, obesity, metabolic syndrome and cancer risk? A two-part systematic review and meta-analysis protocol to estimate attributability

PubMed Central

Sartorius, B; Sartorius, K; Aldous, C; Madiba, T E; Stefan, C; Noakes, T

2016-01-01

Introduction Linkages between carbohydrates, obesity and cancer continue to demonstrate conflicting results. Evidence suggests inconclusive direct linkages between carbohydrates and specific cancers. Conversely, obesity has been strongly linked to a wide range of cancers. The purpose of the study is to explore linkages between carbohydrate intake and cancer types using a two-step approach. First the study will evaluate the linkages between carbohydrate intake and obesity, potentially stratified by metabolic syndrome status. Second, the estimated attributable fraction of obesity ascribed to carbohydrate intake will be multiplied against obesity attributable fractions for cancer types to give estimated overall attributable fraction for carbohydrate versus cancer type. Methods and analysis We will perform a comprehensive search to identify all possible published and unpublished studies that have assessed risk factors for obesity including dietary carbohydrate intake. Scientific databases, namely PubMed MEDLINE, EMBASE, EBSCOhost and ISI Web of Science will be searched. Following study selection, paper/data acquisition, and data extraction and synthesis, we will appraise the quality of studies and risk of bias, as well as assess heterogeneity. Meta-weighted attributable fractions of obesity due to carbohydrate intake will be estimated after adjusting for other potential confounding factors (eg, physical inactivity, other dietary intake). Furthermore, previously published systematic reviews assessing the cancer-specific risk associated with obesity will also be drawn. These estimates will be linked with the attributability of carbohydrate intake in part 1 to estimate the cancer-specific burden that can be attributed to dietary carbohydrates. This systematic review protocol has been developed according to the ‘Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015’. Ethics and dissemination The current study will be based on published literature and data, and, as such, ethics approval is not required. The final results of this two part systematic review (plus multiplicative calculations) will be published in a relevant international peer-reviewed journal. Trial registration number PROSPERO CRD42015023257. PMID:26729382

Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing

PubMed Central

Nunes, José de Ribamar da Silva; Liu, Shikai; Pértille, Fábio; Perazza, Caio Augusto; Villela, Priscilla Marqui Schmidt; de Almeida-Val, Vera Maria Fonseca; Hilsdorf, Alexandre Wagner Silva; Liu, Zhanjiang; Coutinho, Luiz Lehmann

2017-01-01

Colossoma macropomum, or tambaqui, is the largest native Characiform species found in the Amazon and Orinoco river basins, yet few resources for genetic studies and the genetic improvement of tambaqui exist. In this study, we identified a large number of single-nucleotide polymorphisms (SNPs) for tambaqui and constructed a high-resolution genetic linkage map from a full-sib family of 124 individuals and their parents using the genotyping by sequencing method. In all, 68,584 SNPs were initially identified using minimum minor allele frequency (MAF) of 5%. Filtering parameters were used to select high-quality markers for linkage analysis. We selected 7,734 SNPs for linkage mapping, resulting in 27 linkage groups with a minimum logarithm of odds (LOD) of 8 and maximum recombination fraction of 0.35. The final genetic map contains 7,192 successfully mapped markers that span a total of 2,811 cM, with an average marker interval of 0.39 cM. Comparative genomic analysis between tambaqui and zebrafish revealed variable levels of genomic conservation across the 27 linkage groups which allowed for functional SNP annotations. The large-scale SNP discovery obtained here, allowed us to build a high-density linkage map in tambaqui, which will be useful to enhance genetic studies that can be applied in breeding programs. PMID:28387238

An empirical Bayes method for updating inferences in analysis of quantitative trait loci using information from related genome scans.

PubMed

Zhang, Kui; Wiener, Howard; Beasley, Mark; George, Varghese; Amos, Christopher I; Allison, David B

2006-08-01

Individual genome scans for quantitative trait loci (QTL) mapping often suffer from low statistical power and imprecise estimates of QTL location and effect. This lack of precision yields large confidence intervals for QTL location, which are problematic for subsequent fine mapping and positional cloning. In prioritizing areas for follow-up after an initial genome scan and in evaluating the credibility of apparent linkage signals, investigators typically examine the results of other genome scans of the same phenotype and informally update their beliefs about which linkage signals in their scan most merit confidence and follow-up via a subjective-intuitive integration approach. A method that acknowledges the wisdom of this general paradigm but formally borrows information from other scans to increase confidence in objectivity would be a benefit. We developed an empirical Bayes analytic method to integrate information from multiple genome scans. The linkage statistic obtained from a single genome scan study is updated by incorporating statistics from other genome scans as prior information. This technique does not require that all studies have an identical marker map or a common estimated QTL effect. The updated linkage statistic can then be used for the estimation of QTL location and effect. We evaluate the performance of our method by using extensive simulations based on actual marker spacing and allele frequencies from available data. Results indicate that the empirical Bayes method can account for between-study heterogeneity, estimate the QTL location and effect more precisely, and provide narrower confidence intervals than results from any single individual study. We also compared the empirical Bayes method with a method originally developed for meta-analysis (a closely related but distinct purpose). In the face of marked heterogeneity among studies, the empirical Bayes method outperforms the comparator.

Comprehensive multi-stage linkage analyses identify a locus for adult height on chromosome 3p in a healthy Caucasian population.

PubMed

Ellis, Justine A; Scurrah, Katrina J; Duncan, Anna E; Lamantia, Angela; Byrnes, Graham B; Harrap, Stephen B

2007-04-01

There have been a number of genome-wide linkage studies for adult height in recent years. These studies have yielded few well-replicated loci, and none have been further confirmed by the identification of associated gene variants. The inconsistent results may be attributable to the fact that few studies have combined accurate phenotype measures with informative statistical modelling in healthy populations. We have performed a multi-stage genome-wide linkage analysis for height in 275 adult sibling pairs drawn randomly from the Victorian Family Heart Study (VFHS), a healthy population-based Caucasian cohort. Height was carefully measured in a standardised fashion on regularly calibrated equipment. Following genome-wide identification of a peak Z-score of 3.14 on chromosome 3 at 69 cM, we performed a fine-mapping analysis of this region in an extended sample of 392 two-generation families. We used a number of variance components models that incorporated assortative mating and shared environment effects, and we observed a peak LOD score of approximately 3.5 at 78 cM in four of the five models tested. We also demonstrated that the most prevalent model in the literature gave the worst fit, and the lowest LOD score (2.9) demonstrating the importance of appropriate modelling. The region identified in this study replicates the results of other genome-wide scans of height and bone-related phenotypes, strongly suggesting the presence of a gene important in bone growth on chromosome 3p. Association analyses of relevant candidate genes should identify the genetic variants responsible for the chromosome 3p linkage signal in our population.

BRCA1-linked marker in postmenopausal breast cancer families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Folsom, A.R.; Chen, P.L.; Sellers, T.A.

1994-09-01

A majority of breast and ovarian cancer families and half of the early-onset breast cancer families are linked to markers on 17q (BRCA1). While linkage has been demonstrated in families with premenopausal disease, few studies have tested these markers in families with postmenopausal breast cancer. In the Iowa Women`s Health Study, a population-based study of over 42,000 women, an association of waist-to-hip ratio (WHR) with the risk of postmenopausal breast cancer was found predominantly in women with a positive family history -- this interaction was associated with a 3.2-fold elevated risk. This effect was even more pronounced when the definitionmore » of family history included breast and ovarian cancer, known to be linked to 17q markers. We evaluated evidence for linkage with D17S579, a BRCA-1-linked marker, in 13 families in which the index case had postmenopausal breast cancer. Genotyping for alleles at D17S579 was performed on 84 blood samples. Linkage analysis assumed that the breast cancer trait had an autosomal dominant mode of inheritance with a penetrance of 80%. For the 13 families studied, the maximum lod score was 0.29 at a theta of 0.27. There was significant evidence against tight linkage of breast cancer with D17S579 (theta<0.4). Heterogeneity analysis suggested evidence for the presence of both linked and unlinked families. Partitioning informative families on WHR of the index case suggested heterogeneity. These data suggest that, in a subset of families identified by a postmenopausal breast cancer proband, risk of breast cancer may be mediated by BRCA1, with heterogeneity defined by WHR.« less

Are Cranial Biomechanical Simulation Data Linked to Known Diets in Extant Taxa? A Method for Applying Diet-Biomechanics Linkage Models to Infer Feeding Capability of Extinct Species

PubMed Central

Tseng, Zhijie Jack; Flynn, John J.

2015-01-01

Performance of the masticatory system directly influences feeding and survival, so adaptive hypotheses often are proposed to explain craniodental evolution via functional morphology changes. However, the prevalence of “many-to-one” association of cranial forms and functions in vertebrates suggests a complex interplay of ecological and evolutionary histories, resulting in redundant morphology-diet linkages. Here we examine the link between cranial biomechanical properties for taxa with different dietary preferences in crown clade Carnivora, the most diverse clade of carnivorous mammals. We test whether hypercarnivores and generalists can be distinguished based on cranial mechanical simulation models, and how such diet-biomechanics linkages relate to morphology. Comparative finite element and geometric morphometrics analyses document that predicted bite force is positively allometric relative to skull strain energy; this is achieved in part by increased stiffness in larger skull models and shape changes that resist deformation and displacement. Size-standardized strain energy levels do not reflect feeding preferences; instead, caniform models have higher strain energy than feliform models. This caniform-feliform split is reinforced by a sensitivity analysis using published models for six additional taxa. Nevertheless, combined bite force-strain energy curves distinguish hypercarnivorous versus generalist feeders. These findings indicate that the link between cranial biomechanical properties and carnivoran feeding preference can be clearly defined and characterized, despite phylogenetic and allometric effects. Application of this diet-biomechanics linkage model to an analysis of an extinct stem carnivoramorphan and an outgroup creodont species provides biomechanical evidence for the evolution of taxa into distinct hypercarnivorous and generalist feeding styles prior to the appearance of crown carnivoran clades with similar feeding preferences. PMID:25923776

The Effects of Liberalizing World Agricultural Trade: A Review of Modeling Studies

DTIC Science & Technology

2006-06-01

agricultural policy issues. Like the LINKAGE model analysis, the GTAP-AGR model analysis uses version 6.05 of the GTAP database with a base year of...the 2006 study—fully liberal- izing agricultural policy in equal increments from 2005 through 2010—would increase world economic welfare in 2015 by...Burfisher, ed., Agricultural Policy Reform in the WTO—The Road Ahead, Agricultural Economic Report No. 802 (U.S. Department of Agriculture, Economic

Pedigree data analysis with crossover interference.

PubMed Central

Browning, Sharon

2003-01-01

We propose a new method for calculating probabilities for pedigree genetic data that incorporates crossover interference using the chi-square models. Applications include relationship inference, genetic map construction, and linkage analysis. The method is based on importance sampling of unobserved inheritance patterns conditional on the observed genotype data and takes advantage of fast algorithms for no-interference models while using reweighting to allow for interference. We show that the method is effective for arbitrarily many markers with small pedigrees. PMID:12930760

Significant Admixture Linkage Disequilibrium across 30 cM around the FY Locus in African Americans

PubMed Central

Lautenberger, James A.; Stephens, J. Claiborne; O'Brien, Stephen J.; Smith, Michael W.

2000-01-01

Scientists, to understand the importance of allelic polymorphisms on phenotypes that are quantitative and environmentally interacting, are now turning to population-association screens, especially in instances in which pedigree analysis is difficult. Because association screens require linkage disequilibrium between markers and disease loci, maximizing the degree of linkage disequilibrium increases the chances of discovering functional gene-marker associations. One theoretically valid approach—mapping by admixture linkage disequilibrium (MALD), using recently admixed African Americans—is empirically evaluated here by measurement of marker associations with 15 short tandem repeats (STRs) and an insertion/deletion polymorphism of the AT3 locus in a 70-cM segment at 1q22-23, around the FY (Duffy) locus. The FY polymorphism (−46T→C) disrupts the GATA promoter motif, specifically blocking FY erythroid expression and has a nearly fixed allele-frequency difference between European Americans and native Africans that is likely a consequence of a selective advantage of FY−/− in malaria infections. Analysis of linkage disequilibrium around the FY gene has indicated that there is strong and consistent linkage disequilibrium between FY and three flanking loci (D1S303, SPTA1, and D1S484) spanning 8 cM. We observed significant linkage-disequilibrium signals over a 30-cM region from −4.4 to 16.3 cM (from D1S2777 to D1S196) for STRs and at 26.4 cM (AT3), which provided quantitative estimates of centimorgan limits, by MALD assessment in African American population-association analyses, of 5–10 cM. PMID:10712211

Chromosome 14 and late-onset familial alzheimer disease (FAD)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schellenberg, G.D.; Anderson, L.; Nemens, E.

1993-09-01

Familial Alzheimer disease (FAD) is genetically heterogeneous. Two loci responsible for early-onset FAD have been identified: the amyloid precursor protein gene on chromosome 21 and the as-yet-unidentified locus on chromosome 14. The genetics of late-onset FAD is unresolved. Maximum-likelihood, affected-pedigree-member (APM), and sib-pair analysis were used, in 49 families with a mean age at onset [>=]60 years, to determine whether the chromosome 14 locus is responsible for late-onset FAD. The markers used were D14S53, D14S43, and D14S52. The LOD score method was used to test for linkage of late-onset FAD to the chromosome 14 markers, under three different models: age-dependentmore » penetrance, an affected-only analysis, and age-dependent penetrance with allowance for possible age-dependent sporadic cases. No evidence for linkage was obtained under any of these conditions for the late-onset kindreds, and strong evidence against linkage (LOD score [>=]2.0) to this region was obtained. Heterogeneity tests of the LOD score results for the combined group of families (early onset, Volga Germans, and late onset) favored the hypothesis of linkage to chromosome 14 with genetic heterogeneity. The positive results are primarily from early-onset families. APM analysis gave significant evidence for linkage of D14S43 and D14S52 to FAD in early-onset kindreds (P<.02). No evidence for linkage was found for the entire late-onset family group. Significant evidence for linkage to D14S52, however, was found for a subgroup of families of intermediate age at onset (mean age at onset [>=]60 years and <70 years). These results indicate that the chromosome 14 locus is not responsible for Alzheimer disease in most late-onset FAD kindreds but could play a role in a subset of these kindreds. 37 refs., 1 fig., 6 tabs.« less

A Saturated Genetic Linkage Map of Autotetraploid Alfalfa (Medicago sativa L.) Developed Using Genotyping-by-Sequencing Is Highly Syntenous with the Medicago truncatula Genome

PubMed Central

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

2014-01-01

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. PMID:25147192

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

PubMed

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.

X-linked infantile spinal muscular atrophy: clinical definition and molecular mapping.

PubMed

Dressman, Devin; Ahearn, Mary Ellen; Yariz, Kemal O; Basterrecha, Hugo; Martínez, Francisco; Palau, Francesc; Barmada, M Michael; Clark, Robin Dawn; Meindl, Alfons; Wirth, Brunhilde; Hoffman, Eric P; Baumbach-Reardon, Lisa

2007-01-01

X-linked infantile spinal-muscular atrophy (XL-SMA) is a rare disorder, which presents with the clinical characteristics of hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and death in infancy. We have previously reported a single family with XL-SMA that mapped to Xp11.3-q11.2. Here we report further clinical description of XL-SMA plus an additional seven unrelated (XL-SMA) families from North America and Europe that show linkage data consistent with the same region. We first investigated linkage to the candidate disease gene region using microsatellite repeat markers. We further saturated the candidate disease gene region using polymorphic microsatellite repeat markers and single nucleotide polymorphisms in an effort to narrow the critical region. Two-point and multipoint linkage analysis was performed using the Allegro software package. Linkage analysis of all XL-SMA families displayed linkage consistent with the original XL-SMA region. The addition of new families and new markers has narrowed the disease gene interval for a XL-SMA locus between SNP FLJ22843 near marker DXS 8080 and SNP ARHGEF9 which is near DXS7132 (Xp11.3-Xq11.1).

Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder.

PubMed Central

Duffy, A; Turecki, G; Grof, P; Cavazzoni, P; Grof, E; Joober, R; Ahrens, B; Berghöfer, A; Müller-Oerlinghausen, B; Dvoráková, M; Libigerová, E; Vojtĕchovský, M; Zvolský, P; Nilsson, A; Licht, R W; Rasmussen, N A; Schou, M; Vestergaard, P; Holzinger, A; Schumann, C; Thau, K; Robertson, C; Rouleau, G A; Alda, M

2000-01-01

OBJECTIVE: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. DESIGN: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. PARTICIPANTS: A total of 138 patients with bipolar 1 disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. OUTCOME MEASURES: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. RESULTS: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. CONCLUSIONS: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder. PMID:11022400

Action of transglucosidase from Aspergillus niger on maltoheptaose and [U-(13)C]maltose.

PubMed

Ota, Masafumi; Okamoto, Takeshi; Wakabayashi, Hidehiko

2009-03-10

Oligosaccharides synthesized from a mixture of maltoheptaose and [U-(13)C]maltose with transglucosidase [EC 2.4.1.24] from Aspergillus niger were investigated. When the reaction mixture was incubated at 15 degrees C for 1h, several types of oligosaccharides with DP (degree of polymerization) 2 to DP8 containing alpha-D-Glcp-(1-->6)-maltoheptaose were detected by liquid chromatography-mass spectrometry (LC-MS) and methylation analysis. Most of these compounds consisted of alpha-(1-->4) linkages in the main chain and alpha-(1-->6) linkages at the non-reducing ends. However, when the reaction mixture was incubated for 96h, most of these products were converted into oligosaccharides with DP2 to DP5 consisting of only alpha-(1-->6) linkages. These results suggested that A. niger transglucosidase rapidly transferred glucosyl residues to maltooligosaccharides, and gradually hydrolyzed both alpha-(1-->4) linkages and alpha-(1-->6) linkages at the non-reducing end, and transformed these into smaller molecules of mainly alpha-(1-->6) linkages.

Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup’ik) population

PubMed Central

Vaughan, Laura Kelly; Wiener, Howard W.; Aslibekyan, Stella; Allison, David B.; Havel, Peter J.; Stanhope, Kimber L.; O’Brien, Diane M.; Hopkins, Scarlett E.; Lemas, Dominick J.; Boyer, Bert B.; Tiwari, Hemant K.

2015-01-01

Objective To identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup’ik people. Material and Methods We measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks. Results We observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004). Conclusions This study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup’ik people. PMID:25772781

Linkage and association analysis of obesity traits reveals novel loci and interactions with dietary n-3 fatty acids in an Alaska Native (Yup'ik) population.

PubMed

Vaughan, Laura Kelly; Wiener, Howard W; Aslibekyan, Stella; Allison, David B; Havel, Peter J; Stanhope, Kimber L; O'Brien, Diane M; Hopkins, Scarlett E; Lemas, Dominick J; Boyer, Bert B; Tiwari, Hemant K

2015-06-01

To identify novel genetic markers of obesity-related traits and to identify gene-diet interactions with n-3 polyunsaturated fatty acid (n-3 PUFA) intake in Yup'ik people. We measured body composition, plasma adipokines and ghrelin in 982 participants enrolled in the Center for Alaska Native Health Research (CANHR) Study. We conducted a genome-wide SNP linkage scan and targeted association analysis, fitting additional models to investigate putative gene-diet interactions. Finally, we performed bioinformatic analysis to uncover likely candidate genes within the identified linkage peaks. We observed evidence of linkage for all obesity-related traits, replicating previous results and identifying novel regions of interest for adiponectin (10q26.13-2) and thigh circumference (8q21.11-13). Bioinformatic analysis revealed DOCK1, PTPRE (10q26.13-2) and FABP4 (8q21.11-13) as putative candidate genes in the newly identified regions. Targeted SNP analysis under the linkage peaks identified associations between three SNPs and obesity-related traits: rs1007750 on chromosome 8 and thigh circumference (P=0.0005), rs878953 on chromosome 5 and thigh skinfold (P=0.0004), and rs1596854 on chromosome 11 for waist circumference (P=0.0003). Finally, we showed that n-3 PUFA modified the association between obesity related traits and two additional variants (rs2048417 on chromosome 3 for adiponectin, P for interaction=0.0006 and rs730414 on chromosome 11 for percentage body fat, P for interaction=0.0004). This study presents evidence of novel genomic regions and gene-diet interactions that may contribute to the pathophysiology of obesity-related traits among Yup'ik people. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular analysis and test of linkage between the FMR-I gene and infantile autism in multiplex families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hallmayer, J.; Pintado, E.; Lotspeich, L.

Approximately 2%-5% of autistic children show cytogenetic evidence of the fragile X syndrome. This report tests whether infantile autism in multiplex autism families arises from an unusual manifestion of the fragile X syndrome. This could arise either by expansion of the (CGG)n trinucleotide repeat in FMR-1 or from a mutation elsewhere in the gene. We studied 35 families that met stringent criteria for multiplex autism. Amplification of the trinucleotide repeat and analysis of methylation status were performed in 79 autistic children and in 31 of their unaffected siblings by Southern blot analysis. No examples of amplified repeats were seen inmore » the autistic or control children or in their parents or grandparents. We next examined the hypothesis that there was a mutation elsewhere in the FMR-1 gene, by linkage analysis in 32 of these families. We tested four different dominant models and a recessive model. Linkage to FMR-1 could be excluded (lod score between -24 and -62) in all models by using probes DXS548, FRAXAC1, and FRAXAC2 and the CGG repeat itself. Tests for heterogeneity in this sample were negative, and the occurrence of positive lod scores in this data set could be attributed to chance. Analysis of the data by the affected-sib method also did not show evidence for linkage of any marker to autism. These results enable us to reject the hypothesis that multiplex autism arises from expansion of the (CGG)n trinucleotide repeat in FMR-1. Further, because the overall lod scores for all probes in all models tested were highly negative, linkage to FMR-1 can also be ruled out in multiplex autistic families. 35 refs., 2 figs., 5 tabs.« less

The power to detect linkage in complex disease by means of simple LOD-score analyses.

PubMed Central

Greenberg, D A; Abreu, P; Hodge, S E

1998-01-01

Maximum-likelihood analysis (via LOD score) provides the most powerful method for finding linkage when the mode of inheritance (MOI) is known. However, because one must assume an MOI, the application of LOD-score analysis to complex disease has been questioned. Although it is known that one can legitimately maximize the maximum LOD score with respect to genetic parameters, this approach raises three concerns: (1) multiple testing, (2) effect on power to detect linkage, and (3) adequacy of the approximate MOI for the true MOI. We evaluated the power of LOD scores to detect linkage when the true MOI was complex but a LOD score analysis assumed simple models. We simulated data from 14 different genetic models, including dominant and recessive at high (80%) and low (20%) penetrances, intermediate models, and several additive two-locus models. We calculated LOD scores by assuming two simple models, dominant and recessive, each with 50% penetrance, then took the higher of the two LOD scores as the raw test statistic and corrected for multiple tests. We call this test statistic "MMLS-C." We found that the ELODs for MMLS-C are >=80% of the ELOD under the true model when the ELOD for the true model is >=3. Similarly, the power to reach a given LOD score was usually >=80% that of the true model, when the power under the true model was >=60%. These results underscore that a critical factor in LOD-score analysis is the MOI at the linked locus, not that of the disease or trait per se. Thus, a limited set of simple genetic models in LOD-score analysis can work well in testing for linkage. PMID:9718328

The power to detect linkage in complex disease by means of simple LOD-score analyses.

PubMed

Greenberg, D A; Abreu, P; Hodge, S E

1998-09-01

Maximum-likelihood analysis (via LOD score) provides the most powerful method for finding linkage when the mode of inheritance (MOI) is known. However, because one must assume an MOI, the application of LOD-score analysis to complex disease has been questioned. Although it is known that one can legitimately maximize the maximum LOD score with respect to genetic parameters, this approach raises three concerns: (1) multiple testing, (2) effect on power to detect linkage, and (3) adequacy of the approximate MOI for the true MOI. We evaluated the power of LOD scores to detect linkage when the true MOI was complex but a LOD score analysis assumed simple models. We simulated data from 14 different genetic models, including dominant and recessive at high (80%) and low (20%) penetrances, intermediate models, and several additive two-locus models. We calculated LOD scores by assuming two simple models, dominant and recessive, each with 50% penetrance, then took the higher of the two LOD scores as the raw test statistic and corrected for multiple tests. We call this test statistic "MMLS-C." We found that the ELODs for MMLS-C are >=80% of the ELOD under the true model when the ELOD for the true model is >=3. Similarly, the power to reach a given LOD score was usually >=80% that of the true model, when the power under the true model was >=60%. These results underscore that a critical factor in LOD-score analysis is the MOI at the linked locus, not that of the disease or trait per se. Thus, a limited set of simple genetic models in LOD-score analysis can work well in testing for linkage.

Rapid genotyping by low-coverage resequencing to construct genetic linkage maps of fungi: a case study in Lentinula edodes

PubMed Central

2013-01-01

Background Genetic linkage maps are important tools in breeding programmes and quantitative trait analyses. Traditional molecular markers used for genotyping are limited in throughput and efficiency. The advent of next-generation sequencing technologies has facilitated progeny genotyping and genetic linkage map construction in the major grains. However, the applicability of the approach remains untested in the fungal system. Findings Shiitake mushroom, Lentinula edodes, is a basidiomycetous fungus that represents one of the most popular cultivated edible mushrooms. Here, we developed a rapid genotyping method based on low-coverage (~0.5 to 1.5-fold) whole-genome resequencing. We used the approach to genotype 20 single-spore isolates derived from L. edodes strain L54 and constructed the first high-density sequence-based genetic linkage map of L. edodes. The accuracy of the proposed genotyping method was verified experimentally with results from mating compatibility tests and PCR-single-strand conformation polymorphism on a few known genes. The linkage map spanned a total genetic distance of 637.1 cM and contained 13 linkage groups. Two hundred sequence-based markers were placed on the map, with an average marker spacing of 3.4 cM. The accuracy of the map was confirmed by comparing with previous maps the locations of known genes such as matA and matB. Conclusions We used the shiitake mushroom as an example to provide a proof-of-principle that low-coverage resequencing could allow rapid genotyping of basidiospore-derived progenies, which could in turn facilitate the construction of high-density genetic linkage maps of basidiomycetous fungi for quantitative trait analyses and improvement of genome assembly. PMID:23915543

One-Water Hydrologic Flow Model (MODFLOW-OWHM)

USGS Publications Warehouse

Hanson, Randall T.; Boyce, Scott E.; Schmid, Wolfgang; Hughes, Joseph D.; Mehl, Steffen W.; Leake, Stanley A.; Maddock, Thomas; Niswonger, Richard G.

2014-01-01

The One-Water Hydrologic Flow Model (MF-OWHM) is a MODFLOW-based integrated hydrologic flow model (IHM) that is the most complete version, to date, of the MODFLOW family of hydrologic simulators needed for the analysis of a broad range of conjunctive-use issues. Conjunctive use is the combined use of groundwater and surface water. MF-OWHM allows the simulation, analysis, and management of nearly all components of human and natural water movement and use in a physically-based supply-and-demand framework. MF-OWHM is based on the Farm Process for MODFLOW-2005 (MF-FMP2) combined with Local Grid Refinement (LGR) for embedded models to allow use of the Farm Process (FMP) and Streamflow Routing (SFR) within embedded grids. MF-OWHM also includes new features such as the Surface-water Routing Process (SWR), Seawater Intrusion (SWI), and Riparian Evapotrasnpiration (RIP-ET), and new solvers such as Newton-Raphson (NWT) and nonlinear preconditioned conjugate gradient (PCGN). This IHM also includes new connectivities to expand the linkages for deformation-, flow-, and head-dependent flows. Deformation-dependent flows are simulated through the optional linkage to simulated land subsidence with a vertically deforming mesh. Flow-dependent flows now include linkages between the new SWR with SFR and FMP, as well as connectivity with embedded models for SFR and FMP through LGR. Head-dependent flows now include a modified Hydrologic Flow Barrier Package (HFB) that allows optional transient HFB capabilities, and the flow between any two layers that are adjacent along a depositional or erosional boundary or displaced along a fault. MF-OWHM represents a complete operational hydrologic model that fully links the movement and use of groundwater, surface water, and imported water for consumption by irrigated agriculture, but also of water used in urban areas and by natural vegetation. Supply and demand components of water use are analyzed under demand-driven and supply-constrained conditions. From large- to small-scale settings, MF-OWHM has the unique set of capabilities to simulate and analyze historical, present, and future conjunctive-use conditions. MF-OWHM is especially useful for the analysis of agricultural water use where few data are available for pumpage, land use, or agricultural information. The features presented in this IHM include additional linkages with SFR, SWR, Drain-Return (DRT), Multi-Node Wells (MNW1 and MNW2), and Unsaturated-Zone Flow (UZF). Thus, MF-OWHM helps to reduce the loss of water during simulation of the hydrosphere and helps to account for “all of the water everywhere and all of the time.” In addition to groundwater, surface-water, and landscape budgets, MF-OWHM provides more options for observations of land subsidence, hydraulic properties, and evapotranspiration (ET) than previous models. Detailed landscape budgets combined with output of estimates of actual evapotranspiration facilitates linkage to remotely sensed observations as input or as additional observations for parameter estimation or water-use analysis. The features of FMP have been extended to allow for temporally variable water-accounting units (farms) that can be linked to land-use models and the specification of both surface-water and groundwater allotments to facilitate sustainability analysis and connectivity to the Groundwater Management Process (GWM). An example model described in this report demonstrates the application of MF-OWHM with the addition of land subsidence and a vertically deforming mesh, delayed recharge through an unsaturated zone, rejected infiltration in a riparian area, changes in demand caused by deficiency in supply, and changes in multi-aquifer pumpage caused by constraints imposed through the Farm Process and the MNW2 Package, and changes in surface water such as runoff, streamflow, and canal flows through SFR and SWR linkages.

An Autosomal Genetic Linkage Map of the Sheep Genome

PubMed Central

Crawford, A. M.; Dodds, K. G.; Ede, A. J.; Pierson, C. A.; Montgomery, G. W.; Garmonsway, H. G.; Beattie, A. E.; Davies, K.; Maddox, J. F.; Kappes, S. W.; Stone, R. T.; Nguyen, T. C.; Penty, J. M.; Lord, E. A.; Broom, J. E.; Buitkamp, J.; Schwaiger, W.; Epplen, J. T.; Matthew, P.; Matthews, M. E.; Hulme, D. J.; Beh, K. J.; McGraw, R. A.; Beattie, C. W.

1995-01-01

We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation fullsib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum number of informative meioses within the mapping flock was 222. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes. PMID:7498748

A Genome Scan Conducted in a Multigenerational Pedigree with Convergent Strabismus Supports a Complex Genetic Determinism

PubMed Central

Georges, Anouk; Cambisano, Nadine; Ahariz, Naïma; Karim, Latifa; Georges, Michel

2013-01-01

A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree. PMID:24376720

A genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.

PubMed

Georges, Anouk; Cambisano, Nadine; Ahariz, Naïma; Karim, Latifa; Georges, Michel

2013-01-01

A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree.

Planning and environment linkages program : a guide to measuring progress in linking transportation planning and environmental analysis

DOT National Transportation Integrated Search

2009-12-01

Transportation agencies use a variety of metrics to document progress toward achieving specific goals and objectives. This guide, developed by Federal Highway Administration (FHWA) Planning and Environmental Linkages (PEL) program, is intended to hel...

Genes, age, and alcoholism: analysis of GAW14 data.

PubMed

Apprey, Victor; Afful, Joseph; Harrell, Jules P; Taylor, Robert E; Bonney, George E

2005-12-30

A genetic analysis of age of onset of alcoholism was performed on the Collaborative Study on the Genetics of Alcoholism data released for Genetic Analysis Workshop 14. Our study illustrates an application of the log-normal age of onset model in our software Genetic Epidemiology Models (GEMs). The phenotype ALDX1 of alcoholism was studied. The analysis strategy was to first find the markers of the Affymetrix SNP dataset with significant association with age of onset, and then to perform linkage analysis on them. ALDX1 revealed strong evidence of linkage for marker tsc0041591 on chromosome 2 and suggestive linkage for marker tsc0894042 on chromosome 3. The largest separation in mean ages of onset of ALDX1 was 19.76 and 24.41 between male smokers who are carriers of the risk allele of tsc0041591 and the non-carriers, respectively. Hence, male smokers who are carriers of marker tsc0041591 on chromosome 2 have an average onset of ALDX1 almost 5 years earlier than non-carriers.

Exploiting Genome Structure in Association Analysis

PubMed Central

Kim, Seyoung

2014-01-01

Abstract A genome-wide association study involves examining a large number of single-nucleotide polymorphisms (SNPs) to identify SNPs that are significantly associated with the given phenotype, while trying to reduce the false positive rate. Although haplotype-based association methods have been proposed to accommodate correlation information across nearby SNPs that are in linkage disequilibrium, none of these methods directly incorporated the structural information such as recombination events along chromosome. In this paper, we propose a new approach called stochastic block lasso for association mapping that exploits prior knowledge on linkage disequilibrium structure in the genome such as recombination rates and distances between adjacent SNPs in order to increase the power of detecting true associations while reducing false positives. Following a typical linear regression framework with the genotypes as inputs and the phenotype as output, our proposed method employs a sparsity-enforcing Laplacian prior for the regression coefficients, augmented by a first-order Markov process along the sequence of SNPs that incorporates the prior information on the linkage disequilibrium structure. The Markov-chain prior models the structural dependencies between a pair of adjacent SNPs, and allows us to look for association SNPs in a coupled manner, combining strength from multiple nearby SNPs. Our results on HapMap-simulated datasets and mouse datasets show that there is a significant advantage in incorporating the prior knowledge on linkage disequilibrium structure for marker identification under whole-genome association. PMID:21548809

Genetic heterogeneity in psoriasis vulgaris based on linkage analyses of a large family material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wahlstroem, J.; Swanbeck, G.; Inerot, A.

1994-09-01

Information on psoriasis among parents and siblings in 14,008 families has been collected. On the basis of this material, evidence for monogenetic autosomal recessive inheritance of psoriasis has recently been presented. Indications from more than one type of non-pustular psoriasis has been obtained from the population genetic data. Molecular genetic linkage analysis of psoriasis to a number of polymorphic genetic markers for a large number of families has been made. It is apparent that there is genetic heterogeneity in a psoriasis population with regard to psoriasis genes. Using the computer program Linkage 5.0 and a formula for heterogeneity, a lodscoremore » over 3.0 for one locus has been obtained. This locus has further been confirmed by several other markers in the vicinity. The locus found is linked to slightly over half of the families, indicating that there are more genetically independent types of psoriasis. The age at onset of those families that are apparently linked to this locus have a slightly higher age at onset than those not linked to that locus but with a considerable overlap. In spite of close coverage of the whole chromosomes number 6 and 17, no linkage has been found in this regions. This indicates that neither the HLA region nor the region earlier found to be involved in one family with psoriasis are primarily involved in our families.« less

The effect of missing data on linkage disequilibrium mapping and haplotype association analysis in the GAW14 simulated datasets

PubMed Central

McCaskie, Pamela A; Carter, Kim W; McCaskie, Simon R; Palmer, Lyle J

2005-01-01

We used our newly developed linkage disequilibrium (LD) plotting software, JLIN, to plot linkage disequilibrium between pairs of single-nucleotide polymorphisms (SNPs) for three chromosomes of the Genetic Analysis Workshop 14 Aipotu simulated population to assess the effect of missing data on LD calculations. Our haplotype analysis program, SIMHAP, was used to assess the effect of missing data on haplotype-phenotype association. Genotype data was removed at random, at levels of 1%, 5%, and 10%, and the LD calculations and haplotype association results for these levels of missingness were compared to those for the complete dataset. It was concluded that ignoring individuals with missing data substantially affects the number of regions of LD detected which, in turn, could affect tagging SNPs chosen to generate haplotypes. PMID:16451612

Privacy-preserving record linkage using Bloom filters

PubMed Central

2009-01-01

Background Combining multiple databases with disjunctive or additional information on the same person is occurring increasingly throughout research. If unique identification numbers for these individuals are not available, probabilistic record linkage is used for the identification of matching record pairs. In many applications, identifiers have to be encrypted due to privacy concerns. Methods A new protocol for privacy-preserving record linkage with encrypted identifiers allowing for errors in identifiers has been developed. The protocol is based on Bloom filters on q-grams of identifiers. Results Tests on simulated and actual databases yield linkage results comparable to non-encrypted identifiers and superior to results from phonetic encodings. Conclusion We proposed a protocol for privacy-preserving record linkage with encrypted identifiers allowing for errors in identifiers. Since the protocol can be easily enhanced and has a low computational burden, the protocol might be useful for many applications requiring privacy-preserving record linkage. PMID:19706187

Privacy-preserving record linkage using Bloom filters.

PubMed

Schnell, Rainer; Bachteler, Tobias; Reiher, Jörg

2009-08-25

Combining multiple databases with disjunctive or additional information on the same person is occurring increasingly throughout research. If unique identification numbers for these individuals are not available, probabilistic record linkage is used for the identification of matching record pairs. In many applications, identifiers have to be encrypted due to privacy concerns. A new protocol for privacy-preserving record linkage with encrypted identifiers allowing for errors in identifiers has been developed. The protocol is based on Bloom filters on q-grams of identifiers. Tests on simulated and actual databases yield linkage results comparable to non-encrypted identifiers and superior to results from phonetic encodings. We proposed a protocol for privacy-preserving record linkage with encrypted identifiers allowing for errors in identifiers. Since the protocol can be easily enhanced and has a low computational burden, the protocol might be useful for many applications requiring privacy-preserving record linkage.

Analysis of the linkage between rain and flood regime and its application to regional flood frequency estimation

NASA Astrophysics Data System (ADS)

Cunderlik, Juraj M.; Burn, Donald H.

2002-04-01

Improving techniques of flood frequency estimation at ungauged sites is one of the foremost goals of contemporary hydrology. River flood regime is a resultant reflection of a composite catchment hydrologic response to flood producing processes. In this sense the process of identifying homogeneous pooling groups can be plausibly based on catchment similarity in flood regime. Unfortunately the application of any pooling approach that is based on flood regime is restricted to gauged sites. Because flood regime can be markedly determined by rainfall regime, catchment similarity in rainfall regime can be an alternative option for identifying flood frequency pooling groups. An advantage of such a pooling approach is that rainfall data are usually spatially and temporary more abundant than flood data and the approach can also be applied at ungauged sites. Therefore in this study we have quantified the linkage between rainfall and flood regime and explored the appropriateness of substituting rainfall regime for flood regime in regional pooling schemes. Two different approaches to describing rainfall regime similarity using tools of directional statistics have been tested and used for evaluation of the potential of rainfall regime for identification of hydrologically homogeneous pooling groups. The outputs were compared to an existing pooling framework adopted in the Flood Estimation Handbook. The results demonstrate that regional pooling based on rainfall regime information leads to a high number of initially homogeneous groups and seems to be a sound pooling alternative for catchments with a close linkage between rain and flood regimes.

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

PubMed

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, Miina; 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

2007-09-01

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. We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry. Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01). Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.

Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study.

PubMed

Arya, Rector; Lehman, Donna; Hunt, Kelly J; Schneider, Jennifer; Almasy, Laura; Blangero, John; Stern, Michael P; Duggirala, Ravindranath

2003-12-31

Epidemiological studies have indicated that obesity and low high-density lipoprotein (HDL) levels are strong cardiovascular risk factors, and that these traits are inversely correlated. Despite the belief that these traits are correlated in part due to pleiotropy, knowledge on specific genes commonly affecting obesity and dyslipidemia is very limited. To address this issue, we first conducted univariate multipoint linkage analysis for body mass index (BMI) and HDL-C to identify loci influencing variation in these phenotypes using Framingham Heart Study data relating to 1702 subjects distributed across 330 pedigrees. Subsequently, we performed bivariate multipoint linkage analysis to detect common loci influencing covariation between these two traits. We scanned the genome and identified a major locus near marker D6S1009 influencing variation in BMI (LOD = 3.9) using the program SOLAR. We also identified a major locus for HDL-C near marker D2S1334 on chromosome 2 (LOD = 3.5) and another region near marker D6S1009 on chromosome 6 with suggestive evidence for linkage (LOD = 2.7). Since these two phenotypes have been independently mapped to the same region on chromosome 6q, we used the bivariate multipoint linkage approach using SOLAR. The bivariate linkage analysis of BMI and HDL-C implicated the genetic region near marker D6S1009 as harboring a major gene commonly influencing these phenotypes (bivariate LOD = 6.2; LODeq = 5.5) and appears to improve power to map the correlated traits to a region, precisely. We found substantial evidence for a quantitative trait locus with pleiotropic effects, which appears to influence both BMI and HDL-C phenotypes in the Framingham data.

Dissecting the genetic heterogeneity of myopia susceptibility in an Ashkenazi Jewish population using ordered subset analysis

PubMed Central

Simpson, Claire L.; Wojciechowski, Robert; Ibay, Grace; Stambolian, Dwight

2011-01-01

Purpose Despite many years of research, most of the genetic factors contributing to myopia development remain unknown. Genetic studies have pointed to a strong inherited component, but although many candidate regions have been implicated, few genes have been positively identified. Methods We have previously reported 2 genomewide linkage scans in a population of 63 highly aggregated Ashkenazi Jewish families that identified a locus on chromosome 22. Here we used ordered subset analysis (OSA), conditioned on non-parametric linkage to chromosome 22 to detect other chromosomal regions which had evidence of linkage to myopia in subsets of the families, but not the overall sample. Results Strong evidence of linkage to a 19-cM linkage interval with a peak OSA nonparametric allele-sharing logarithm-of-odds (LOD) score of 3.14 on 20p12-q11.1 (ΔLOD=2.39, empirical p=0.029) was identified in a subset of 20 families that also exhibited strong evidence of linkage to chromosome 22. One other locus also presented with suggestive LOD scores >2.0 on chromosome 11p14-q14 and one locus on chromosome 6q22-q24 had an OSA LOD score=1.76 (ΔLOD=1.65, empirical p=0.02). Conclusions The chromosome 6 and 20 loci are entirely novel and appear linked in a subset of families whose myopia is known to be linked to chromosome 22. The chromosome 11 locus overlaps with the known Myopia-7 (MYP7, OMIM 609256) locus. Using ordered subset analysis allows us to find additional loci linked to myopia in subsets of families, and underlines the complex genetic heterogeneity of myopia even in highly aggregated families and genetically isolated populations such as the Ashkenazi Jews. PMID:21738393

Biocatalytic synthesis of maltodextrin-based acrylates from starch and α-cyclodextrin.

PubMed

Kloosterman, Wouter M J; Spoelstra-van Dijk, Gerda; Loos, Katja

2014-09-01

Novel 2-(β-maltooligooxy)-ethyl (meth)acrylate monomers are successfully synthesized by CGTase from Bacillus macerans catalyzed coupling of 2-(β-glucosyloxy)-ethyl acrylate and methacrylate with α-cyclodextrin or starch. HPLC-UV analysis shows that the CGTase catalyzed reaction yields 2-(β-maltooligooxy)-ethyl acrylates with 1 to 15 glucopyranosyl units. (1) H NMR spectroscopy reveals that the β-linkage in the acceptor molecule is preserved during the CGTase catalyzed coupling reaction, whereas the newly introduced glucose units are attached by α-(1,4)-glycosidic linkages. The synthesized 2-(β-maltooligooxy)-ethyl acrylate monomers are successfully polymerized by aqueous free radical polymerization to yield the comb-shaped glycopolymer poly(2-(β-maltooligooxy)-ethyl acrylate). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New Tools for Learning: A Case of Organizational Problem Analysis Derived from Debriefing Records in a Medical Center

ERIC Educational Resources Information Center

Holzmann, Vered; Mischari, Shoshana; Goldberg, Shoshana; Ziv, Amitai

2012-01-01

Purpose: This article aims to present a unique systematic and validated method for creating a linkage between past experiences and management of future occurrences in an organization. Design/methodology/approach: The study is based on actual data accumulated in a series of projects performed in a major medical center. Qualitative and quantitative…

Analysis of agronomic and domestication traits in a durum x cultivated emmer wheat population using a high-density single nucleotide polymorphism-based linkage map

USDA-ARS?s Scientific Manuscript database

Cultivated emmer wheat (Triticum turgidum ssp. dicoccum) is tetraploid and considered one of the eight founder crops that spawned the Agricultural Revolution about 10,000 years ago. Cultivated emmer has non-free-threshing seed and a somewhat fragile rachis, but mutations in genes governing these an...

The Situation of Children in Iraq: An Assessment Based on the United Nations Convention on the Rights of the Child.

ERIC Educational Resources Information Center

Hijab, Nadia

In accordance with UNICEF mandates requiring a situation analysis prior to preparing a new country program, this report examines causes and linkages between problems affecting women and children in Iraq, identifies necessary actions to realize the rights of women and children, and contributes to the country program strategy for priority…

Privacy-preserving record linkage on large real world datasets.

PubMed

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

2014-08-01

Record linkage typically involves the use of dedicated linkage units who are supplied with personally identifying information to determine individuals from within and across datasets. The personally identifying information supplied to linkage units is separated from clinical information prior to release by data custodians. While this substantially reduces the risk of disclosure of sensitive information, some residual risks still exist and remain a concern for some custodians. In this paper we trial a method of record linkage which reduces privacy risk still further on large real world administrative data. The method uses encrypted personal identifying information (bloom filters) in a probability-based linkage framework. The privacy preserving linkage method was tested on ten years of New South Wales (NSW) and Western Australian (WA) hospital admissions data, comprising in total over 26 million records. No difference in linkage quality was found when the results were compared to traditional probabilistic methods using full unencrypted personal identifiers. This presents as a possible means of reducing privacy risks related to record linkage in population level research studies. It is hoped that through adaptations of this method or similar privacy preserving methods, risks related to information disclosure can be reduced so that the benefits of linked research taking place can be fully realised. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

PubMed

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.

Exploiting rice-sorghum synteny for targeted development of EST-SSRs to enrich the sorghum genetic linkage map.

PubMed

Ramu, P; Kassahun, B; Senthilvel, S; Ashok Kumar, C; Jayashree, B; Folkertsma, R T; Reddy, L Ananda; Kuruvinashetti, M S; Haussmann, B I G; Hash, C T

2009-11-01

The sequencing and detailed comparative functional analysis of genomes of a number of select botanical models open new doors into comparative genomics among the angiosperms, with potential benefits for improvement of many orphan crops that feed large populations. In this study, a set of simple sequence repeat (SSR) markers was developed by mining the expressed sequence tag (EST) database of sorghum. Among the SSR-containing sequences, only those sharing considerable homology with rice genomic sequences across the lengths of the 12 rice chromosomes were selected. Thus, 600 SSR-containing sorghum EST sequences (50 homologous sequences on each of the 12 rice chromosomes) were selected, with the intention of providing coverage for corresponding homologous regions of the sorghum genome. Primer pairs were designed and polymorphism detection ability was assessed using parental pairs of two existing sorghum mapping populations. About 28% of these new markers detected polymorphism in this 4-entry panel. A subset of 55 polymorphic EST-derived SSR markers were mapped onto the existing skeleton map of a recombinant inbred population derived from cross N13 x E 36-1, which is segregating for Striga resistance and the stay-green component of terminal drought tolerance. These new EST-derived SSR markers mapped across all 10 sorghum linkage groups, mostly to regions expected based on prior knowledge of rice-sorghum synteny. The ESTs from which these markers were derived were then mapped in silico onto the aligned sorghum genome sequence, and 88% of the best hits corresponded to linkage-based positions. This study demonstrates the utility of comparative genomic information in targeted development of markers to fill gaps in linkage maps of related crop species for which sufficient genomic tools are not available.

The voluntary community health movement in India: a strengths, weaknesses, opportunities, and threats (SWOT) analysis.

PubMed

Sharma, M; Bhatia, G

1996-12-01

There has been a prolific growth of voluntary organizations in India since independence in 1947. One of the major areas of this growth has been in the field of community health. The purpose of this article is to historically trace the voluntary movement in community health in India, analyze the current status, and predict future trends of voluntary efforts. A review of the literature in the form of a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was the method of this study. Some of the key trends which emerged as the priority areas for progress and for strengthening voluntary organizations in the future were enhancing linkages between health and development; building upon collective force; greater utilization of participatory training; establishing egalitarian and effectual linkages for decision making at the international level; developing self-reliant community-based models; and the need for attaining holistic empowerment at individual, organizational, and community levels through "duty consciousness" as opposed to merely asking for rights.

A Genome-Wide Linkage Scan for Age at Menarche in Three Populations of European Descent

PubMed Central

Anderson, Carl A.; Zhu, Gu; Falchi, Mario; van den Berg, Stéphanie M.; Treloar, Susan A.; Spector, Timothy D.; Martin, Nicholas G.; Boomsma, Dorret I.; Visscher, Peter M.; Montgomery, Grant W.

2008-01-01

Context: Age at menarche (AAM) is an important trait both biologically and socially, a clearly defined event in female pubertal development, and has been associated with many clinically significant phenotypes. Objective: The objective of the study was to identify genetic loci influencing variation in AAM in large population-based samples from three countries. Design/Participants: Recalled AAM data were collected from 13,697 individuals and 4,899 pseudoindependent sister-pairs from three different populations (Australia, The Netherlands, and the United Kingdom) by mailed questionnaire or interview. Genome-wide variance components linkage analysis was implemented on each sample individually and in combination. Results: The mean, sd, and heritability of AAM across the three samples was 13.1 yr, 1.5 yr, and 0.69, respectively. No loci were detected that reached genome-wide significance in the combined analysis, but a suggestive locus was detected on chromosome 12 (logarithm of the odds = 2.0). Three loci of suggestive significance were seen in the U.K. sample on chromosomes 1, 4, and 18 (logarithm of the odds = 2.4, 2.2 and 3.2, respectively). Conclusions: There was no evidence for common highly penetrant variants influencing AAM. Linkage and association suggest that one trait locus for AAM is located on chromosome 12, but further studies are required to replicate these results. PMID:18647812

Family-based linkage and association mapping reveals novel genes affecting Plum pox virus infection in Arabidopsis thaliana.

PubMed

Pagny, Gaëlle; Paulstephenraj, Pauline S; Poque, Sylvain; Sicard, Ophélie; Cosson, Patrick; Eyquard, Jean-Philippe; Caballero, Mélodie; Chague, Aurélie; Gourdon, Germain; Negrel, Lise; Candresse, Thierry; Mariette, Stéphanie; Decroocq, Véronique

2012-11-01

Sharka is a devastating viral disease caused by the Plum pox virus (PPV) in stone fruit trees and few sources of resistance are known in its natural hosts. Since any knowledge gained from Arabidopsis on plant virus susceptibility factors is likely to be transferable to crop species, Arabidopsis's natural variation was searched for host factors essential for PPV infection. To locate regions of the genome associated with susceptibility to PPV, linkage analysis was performed on six biparental populations as well as on multiparental lines. To refine quantitative trait locus (QTL) mapping, a genome-wide association analysis was carried out using 147 Arabidopsis accessions. Evidence was found for linkage on chromosomes 1, 3 and 5 with restriction of PPV long-distance movement. The most relevant signals occurred within a region at the bottom of chromosome 3, which comprises seven RTM3-like TRAF domain-containing genes. Since the resistance mechanism analyzed here is recessive and the rtm3 knockout mutant is susceptible to PPV infection, it suggests that other gene(s) present in the small identified region encompassing RTM3 are necessary for PPV long-distance movement. In consequence, we report here the occurrence of host factor(s) that are indispensable for virus long-distance movement. © 2012 INRA. New Phytologist © 2012 New Phytologist Trust.

A Genetic Linkage Map for Cattle

PubMed Central

Bishop, M. D.; Kappes, S. M.; Keele, J. W.; Stone, R. T.; Sunden, SLF.; Hawkins, G. A.; Toldo, S. S.; Fries, R.; Grosz, M. D.; Yoo, J.; Beattie, C. W.

1994-01-01

We report the most extensive physically anchored linkage map for cattle produced to date. Three-hundred thirteen genetic markers ordered in 30 linkage groups, anchored to 24 autosomal chromosomes (n = 29), the X and Y chromosomes, four unanchored syntenic groups and two unassigned linkage groups spanning 2464 cM of the bovine genome are summarized. The map also assigns 19 type I loci to specific chromosomes and/or syntenic groups and four cosmid clones containing informative microsatellites to chromosomes 13, 25 and 29 anchoring syntenic groups U11, U7 and U8, respectively. This map provides the skeletal framework prerequisite to development of a comprehensive genetic map for cattle and analysis of economic trait loci (ETL). PMID:7908653

An Expressed Sequence Tag (EST)-enriched genetic map of turbot (Scophthalmus maximus): a useful framework for comparative genomics across model and farmed teleosts

PubMed Central

2012-01-01

Background The turbot (Scophthalmus maximus) is a relevant species in European aquaculture. The small turbot genome provides a source for genomics strategies to use in order to understand the genetic basis of productive traits, particularly those related to sex, growth and pathogen resistance. Genetic maps represent essential genomic screening tools allowing to localize quantitative trait loci (QTL) and to identify candidate genes through comparative mapping. This information is the backbone to develop marker-assisted selection (MAS) programs in aquaculture. Expressed sequenced tag (EST) resources have largely increased in turbot, thus supplying numerous type I markers suitable for extending the previous linkage map, which was mostly based on anonymous loci. The aim of this study was to construct a higher-resolution turbot genetic map using EST-linked markers, which will turn out to be useful for comparative mapping studies. Results A consensus gene-enriched genetic map of the turbot was constructed using 463 SNP and microsatellite markers in nine reference families. This map contains 438 markers, 180 EST-linked, clustered at 24 linkage groups. Linkage and comparative genomics evidences suggested additional linkage group fusions toward the consolidation of turbot map according to karyotype information. The linkage map showed a total length of 1402.7 cM with low average intermarker distance (3.7 cM; ~2 Mb). A global 1.6:1 female-to-male recombination frequency (RF) ratio was observed, although largely variable among linkage groups and chromosome regions. Comparative sequence analysis revealed large macrosyntenic patterns against model teleost genomes, significant hits decreasing from stickleback (54%) to zebrafish (20%). Comparative mapping supported particular chromosome rearrangements within Acanthopterygii and aided to assign unallocated markers to specific turbot linkage groups. Conclusions The new gene-enriched high-resolution turbot map represents a useful genomic tool for QTL identification, positional cloning strategies, and future genome assembling. This map showed large synteny conservation against model teleost genomes. Comparative genomics and data mining from landmarks will provide straightforward access to candidate genes, which will be the basis for genetic breeding programs and evolutionary studies in this species. PMID:22747677

Sensitive and Structure-Informative N-Glycosylation Analysis by MALDI-MS; Ionization, Fragmentation, and Derivatization

PubMed Central

Nishikaze, Takashi

2017-01-01

Mass spectrometry (MS) has become an indispensable tool for analyzing post translational modifications of proteins, including N-glycosylated molecules. Because most glycosylation sites carry a multitude of glycans, referred to as “glycoforms,” the purpose of an N-glycosylation analysis is glycoform profiling and glycosylation site mapping. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has unique characteristics that are suited for the sensitive analysis of N-glycosylated products. However, the analysis is often hampered by the inherent physico-chemical properties of N-glycans. Glycans are highly hydrophilic in nature, and therefore tend to show low ion yields in both positive- and negative-ion modes. The labile nature and complicated branched structures involving various linkage isomers make structural characterization difficult. This review focuses on MALDI-MS-based approaches for enhancing analytical performance in N-glycosylation research. In particular, the following three topics are emphasized: (1) Labeling for enhancing the ion yields of glycans and glycopeptides, (2) Negative-ion fragmentation for less ambiguous elucidation of the branched structure of N-glycans, (3) Derivatization for the stabilization and linkage isomer discrimination of sialic acid residues. PMID:28794918

Analyzing the Relative Linkages of Land Use and Hydrologic Variables with Urban Surface Water Quality using Multivariate Techniques

NASA Astrophysics Data System (ADS)

Ahmed, S.; Abdul-Aziz, O. I.

2015-12-01

We used a systematic data-analytics approach to analyze and quantify relative linkages of four stream water quality indicators (total nitrogen, TN; total phosphorus, TP; chlorophyll-a, Chla; and dissolved oxygen, DO) with six land use and four hydrologic variables, along with the potential external (upstream in-land and downstream coastal) controls in highly complex coastal urban watersheds of southeast Florida, U.S.A. Multivariate pattern recognition techniques of principle component and factor analyses, in concert with Pearson correlation analysis, were applied to map interrelations and identify latent patterns of the participatory variables. Relative linkages of the in-stream water quality variables with their associated drivers were then quantified by developing dimensionless partial least squares (PLS) regression model based on standardized data. Model fitting efficiency (R2=0.71-0.87) and accuracy (ratio of root-mean-square error to the standard deviation of the observations, RSR=0.35-0.53) suggested good predictions of the water quality variables in both wet and dry seasons. Agricultural land and groundwater exhibited substantial controls on surface water quality. In-stream TN concentration appeared to be mostly contributed by the upstream water entering from Everglades in both wet and dry seasons. In contrast, watershed land uses had stronger linkages with TP and Chla than that of the watershed hydrologic and upstream (Everglades) components for both seasons. Both land use and hydrologic components showed strong linkages with DO in wet season; however, the land use linkage appeared to be less in dry season. The data-analytics method provided a comprehensive empirical framework to achieve crucial mechanistic insights into the urban stream water quality processes. Our study quantitatively identified dominant drivers of water quality, indicating key management targets to maintain healthy stream ecosystems in complex urban-natural environments near the coast.

Genome-wide linkage scan for maximum and length-dependent knee muscle strength in young men: significant evidence for linkage at chromosome 14q24.3

PubMed Central

De Mars, G; Windelinckx, A; Huygens, W; Peeters, M W; Beunen, G P; Aerssens, J; Vlietinck, R; Thomis, M A I

2008-01-01

Background: Maintenance of high muscular fitness is positively related to bone health, functionality in daily life and increasing insulin sensitivity, and negatively related to falls and fractures, morbidity and mortality. Heritability of muscle strength phenotypes ranges between 31% and 95%, but little is known about the identity of the genes underlying this complex trait. As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to muscle and bone cross-sectional area, isometric knee flexion and extension torque, and torque–length relationship for knee flexors and extensors. Methods: In total, 283 informative male siblings (17–36 years old), belonging to 105 families, were used to conduct a genome-wide SNP-based multipoint linkage analysis. Results: The strongest evidence for linkage was found for the torque–length relationship of the knee flexors at 14q24.3 (LOD  = 4.09; p<10−5). Suggestive evidence for linkage was found at 14q32.2 (LOD  = 3.00; P = 0.005) for muscle and bone cross-sectional area, at 2p24.2 (LOD  = 2.57; p = 0.01) for isometric knee torque at 30° flexion, at 1q21.3, 2p23.3 and 18q11.2 (LOD  = 2.33, 2.69 and 2.21; p<10−4 for all) for the torque–length relationship of the knee extensors and at 18p11.31 (LOD  = 2.39; p = 0.0004) for muscle-mass adjusted isometric knee extension torque. Conclusions: We conclude that many small contributing genes rather than a few important genes are involved in causing variation in different underlying phenotypes of muscle strength. Furthermore, some overlap in promising genomic regions were identified among different strength phenotypes. PMID:18178634

Method to Eliminate Flux Linkage DC Component in Load Transformer for Static Transfer Switch

PubMed Central

2014-01-01

Many industrial and commercial sensitive loads are subject to the voltage sags and interruptions. The static transfer switch (STS) based on the thyristors is applied to improve the power quality and reliability. However, the transfer will result in severe inrush current in the load transformer, because of the DC component in the magnetic flux generated in the transfer process. The inrush current which is always 2~30 p.u. can cause the disoperation of relay protective devices and bring potential damage to the transformer. The way to eliminate the DC component is to transfer the related phases when the residual flux linkage of the load transformer and the prospective flux linkage of the alternate source are equal. This paper analyzes how the flux linkage of each winding in the load transformer changes in the transfer process. Based on the residual flux linkage when the preferred source is completely disconnected, the method to calculate the proper time point to close each phase of the alternate source is developed. Simulation and laboratory experiments results are presented to show the effectiveness of the transfer method. PMID:25133255

Method to eliminate flux linkage DC component in load transformer for static transfer switch.

PubMed

He, Yu; Mao, Chengxiong; Lu, Jiming; Wang, Dan; Tian, Bing

2014-01-01

Many industrial and commercial sensitive loads are subject to the voltage sags and interruptions. The static transfer switch (STS) based on the thyristors is applied to improve the power quality and reliability. However, the transfer will result in severe inrush current in the load transformer, because of the DC component in the magnetic flux generated in the transfer process. The inrush current which is always 2 ~ 30 p.u. can cause the disoperation of relay protective devices and bring potential damage to the transformer. The way to eliminate the DC component is to transfer the related phases when the residual flux linkage of the load transformer and the prospective flux linkage of the alternate source are equal. This paper analyzes how the flux linkage of each winding in the load transformer changes in the transfer process. Based on the residual flux linkage when the preferred source is completely disconnected, the method to calculate the proper time point to close each phase of the alternate source is developed. Simulation and laboratory experiments results are presented to show the effectiveness of the transfer method.

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

PubMed

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.

Genome-wide scan of IQ finds significant linkage to a quantitative trait locus on 2q.

PubMed

Luciano, M; Wright, M J; Duffy, D L; Wainwright, M A; Zhu, G; Evans, D M; Geffen, G M; Montgomery, G W; Martin, N G

2006-01-01

A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2-5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were available for 81% of parents. A variance components analysis which controlled for age and sex effects showed significant linkage for the Cambridge reading test and performance IQ to the same region on chromosome 2, with respective LOD scores of 4.15 and 3.68. Suggestive linkage (LOD score>2.2) for various measures was further supported on chromosomes 6, 7, 11, 14, 21 and 22. Where location of linkage peaks converged for IQ subtests within the same scale, the overall scale score provided increased evidence for linkage to that region over any individual subtest. Association studies of candidate genes, particularly those involved in neural transmission and development, will be directed to genes located under the linkage peaks identified in this study.

SSR-enriched genetic linkage maps of bermudagrass (Cynodon dactylon × transvaalensis), and their comparison with allied plant genomes.

PubMed

Khanal, Sameer; Kim, Changsoo; Auckland, Susan A; Rainville, Lisa K; Adhikari, Jeevan; Schwartz, Brian M; Paterson, Andrew H

2017-04-01

We report SSR-enriched genetic maps of bermudagrass that: (1) reveal partial residual polysomic inheritance in the tetraploid species, and (2) provide insights into the evolution of chloridoid genomes. This study describes genetic linkage maps of two bermudagrass species, Cynodon dactylon (T89) and Cynodon transvaalensis (T574), that integrate heterologous microsatellite markers from sugarcane into frameworks built with single-dose restriction fragments (SDRFs). A maximum likelihood approach was used to construct two separate parental maps from a population of 110 F 1 progeny of a cross between the two parents. The T89 map is based on 291 loci on 34 cosegregating groups (CGs), with an average marker spacing of 12.5 cM. The T574 map is based on 125 loci on 14 CGs, with an average marker spacing of 10.7 cM. Six T89 and one T574 CG(s) deviated from disomic inheritance. Furthermore, marker segregation data and linkage phase analysis revealed partial residual polysomic inheritance in T89, suggesting that common bermudagrass is undergoing diploidization following whole genome duplication (WGD). Twenty-six T89 CGs were coalesced into 9 homo(eo)logous linkage groups (LGs), while 12 T574 CGs were assembled into 9 LGs, both putatively representing the basic chromosome complement (x = 9) of the species. Eight T89 and two T574 CGs remain unassigned. The marker composition of bermudagrass ancestral chromosomes was inferred by aligning T89 and T574 homologs, and used in comparisons to sorghum and rice genome sequences based on 108 and 91 significant blast hits, respectively. Two nested chromosome fusions (NCFs) shared by two other chloridoids (i.e., zoysiagrass and finger millet) and at least three independent translocation events were evident during chromosome number reduction from 14 in the polyploid common ancestor of Poaceae to 9 in Cynodon.

An Enhanced Linkage Map of the Sheep Genome Comprising More Than 1000 Loci

PubMed Central

Maddox, Jillian F.; Davies, Kizanne P.; Crawford, Allan M.; Hulme, Dennis J.; Vaiman, Daniel; Cribiu, Edmond P.; Freking, Bradley A.; Beh, Ken J.; Cockett, Noelle E.; Kang, Nina; Riffkin, Christopher D.; Drinkwater, Roger; Moore, Stephen S.; Dodds, Ken G.; Lumsden, Joanne M.; van Stijn, Tracey C.; Phua, Sin H.; Adelson, David L.; Burkin, Heather R.; Broom, Judith E.; Buitkamp, Johannes; Cambridge, Lisa; Cushwa, William T.; Gerard, Emily; Galloway, Susan M.; Harrison, Blair; Hawken, Rachel J.; Hiendleder, Stefan; Henry, Hannah M.; Medrano, Juan F.; Paterson, Korena A.; Schibler, Laurent; Stone, Roger T.; van Hest, Beryl

2001-01-01

A medium-density linkage map of the ovine genome has been developed. Marker data for 550 new loci were generated and merged with the previous sheep linkage map. The new map comprises 1093 markers representing 1062 unique loci (941 anonymous loci, 121 genes) and spans 3500 cM (sex-averaged) for the autosomes and 132 cM (female) on the X chromosome. There is an average spacing of 3.4 cM between autosomal loci and 8.3 cM between highly polymorphic [polymorphic information content (PIC) ≥ 0.7] autosomal loci. The largest gap between markers is 32.5 cM, and the number of gaps of >20 cM between loci, or regions where loci are missing from chromosome ends, has been reduced from 40 in the previous map to 6. Five hundred and seventy-three of the loci can be ordered on a framework map with odds of >1000 : 1. The sheep linkage map contains strong links to both the cattle and goat maps. Five hundred and seventy-two of the loci positioned on the sheep linkage map have also been mapped by linkage analysis in cattle, and 209 of the loci mapped on the sheep linkage map have also been placed on the goat linkage map. Inspection of ruminant linkage maps indicates that the genomic coverage by the current sheep linkage map is comparable to that of the available cattle maps. The sheep map provides a valuable resource to the international sheep, cattle, and goat gene mapping community. PMID:11435411

Linkage to chromosome 2q36.1 in autosomal dominant Dandy-Walker malformation with occipital cephalocele and evidence for genetic heterogeneity

PubMed Central

Jalali, Ali; Aldinger, Kimberly A.; Chary, Ajit; Mclone, David G.; Bowman, Robin M.; Le, Luan Cong; Jardine, Phillip; Newbury-Ecob, Ruth; Mallick, Andrew; Jafari, Nadereh; Russell, Eric J.; Curran, John; Nguyen, Pam; Ouahchi, Karim; Lee, Charles; Dobyns, William B.; Millen, Kathleen J.; Pina-Neto, Joao M.; Kessler, John A.; Bassuk, Alexander G.

2010-01-01

We previously reported a Vietnamese-American family with isolated autosomal dominant occipital cephalocele. Upon further neuroimaging studies, we have recharacterized this condition as autosomal dominant Dandy-Walker with occipital cephalocele (ADDWOC). A similar ADDWOC family from Brazil was also recently described. To determine the genetic etiology of ADDWOC, we performed genome-wide linkage analysis on members of the Vietnamese-American and Brazilian pedigrees. Linkage analysis of the Vietnamese-American family identified the ADDWOC causative locus on chromosome 2q36.1 with a multipoint parametric LOD score of 3.3, while haplotype analysis refined the locus to 1.1 Mb. Sequencing of the five known genes in this locus did not identify any protein-altering mutations. However, a terminal deletion of chromosome 2 in a patient with an isolated case of Dandy-Walker malformation also encompassed the 2q36.1 chromosomal region. The Brazilian pedigree did not show linkage to this 2q36.1 region. Taken together, these results demonstrate a locus for ADDWOC on 2q36.1 and also suggest locus heterogeneity for ADDWOC. PMID:18204864

Identification of a herpes simplex labialis susceptibility region on human chromosome 21.

PubMed

Hobbs, Maurine R; Jones, Brandt B; Otterud, Brith E; Leppert, Mark; Kriesel, John D

2008-02-01

Most of the United States population is infected with either herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, or both. Reactivations of HSV-1 infection cause herpes simplex labialis (HSL; cold sores or fever blisters), which is the most common recurring viral infection in humans. To investigate the possibility of a human genetic component conferring resistance or susceptibility to cold sores (i.e., a HSL susceptibility gene), we conducted a genetic linkage analysis that included serotyping and phenotyping 421 individuals from 39 families enrolled in the Utah Genetic Reference Project. Linkage analysis identified a 2.5-Mb nonrecombinant region of interest on the long arm of human chromosome 21, with a multipoint logarithm of odds score of 3.9 noted near marker abmc65 (D21S409). Nonparametric linkage analysis of the data also provided strong evidence for linkage (P = .0005). This region of human chromosome 21 contains 6 candidate genes for herpes susceptibility. The development of frequent cold sores is associated with a region on the long arm of human chromosome 21. This region contains several candidate genes that could influence the frequency of outbreaks of HSL.

Multifunctional Polymers and Composites for Self-Healing Applications

DTIC Science & Technology

2006-09-30

linkages (Chen et al. 2002), and a phase separated system based on polydimethylsiloxane (Cho et al. 2006). Self-healing occurs when monomer is released...WCI6 is shown in Figure 1.1a. The average particle sizes determined by analysis of SEM images for all three delivery methods are listed in Table 1.1...were then sieved and the beads smaller than 355 um were kept for further study. Elemental analysis of the wax beads revealed that the concentration of

Genomic rearrangements and signatures of breeding in the allo-octoploid strawberry as revealed through an allele dose based SSR linkage map

PubMed Central

2014-01-01

Background Breeders in the allo-octoploid strawberry currently make little use of molecular marker tools. As a first step of a QTL discovery project on fruit quality traits and resistance to soil-borne pathogens such as Phytophthora cactorum and Verticillium we built a genome-wide SSR linkage map for the cross Holiday x Korona. We used the previously published MADCE method to obtain full haplotype information for both of the parental cultivars, facilitating in-depth studies on their genomic organisation. Results The linkage map incorporates 508 segregating loci and represents each of the 28 chromosome pairs of octoploid strawberry, spanning an estimated length of 2050 cM. The sub-genomes are denoted according to their sequence divergence from F. vesca as revealed by marker performance. The map revealed high overall synteny between the sub-genomes, but also revealed two large inversions on LG2C and LG2D, of which the latter was confirmed using a separate mapping population. We discovered interesting breeding features within the parental cultivars by in-depth analysis of our haplotype data. The linkage map-derived homozygosity level of Holiday was similar to the pedigree-derived inbreeding level (33% and 29%, respectively). For Korona we found that the observed homozygosity level was over three times higher than expected from the pedigree (13% versus 3.6%). This could indicate selection pressure on genes that have favourable effects in homozygous states. The level of kinship between Holiday and Korona derived from our linkage map was 2.5 times higher than the pedigree-derived value. This large difference could be evidence of selection pressure enacted by strawberry breeders towards specific haplotypes. Conclusion The obtained SSR linkage map provides a good base for QTL discovery. It also provides the first biologically relevant basis for the discernment and notation of sub-genomes. For the first time, we revealed genomic rearrangements that were verified in a separate mapping population. We believe that haplotype information will become increasingly important in identifying marker-trait relationships and regions that are under selection pressure within breeding material. Our attempt at providing a biological basis for the discernment of sub-genomes warrants follow-up studies to streamline the naming of the sub-genomes among different octoploid strawberry maps. PMID:24581289

Genomic rearrangements and signatures of breeding in the allo-octoploid strawberry as revealed through an allele dose based SSR linkage map.

PubMed

van Dijk, Thijs; Pagliarani, Giulia; Pikunova, Anna; Noordijk, Yolanda; Yilmaz-Temel, Hulya; Meulenbroek, Bert; Visser, Richard G F; van de Weg, Eric

2014-03-01

Breeders in the allo-octoploid strawberry currently make little use of molecular marker tools. As a first step of a QTL discovery project on fruit quality traits and resistance to soil-borne pathogens such as Phytophthora cactorum and Verticillium we built a genome-wide SSR linkage map for the cross Holiday x Korona. We used the previously published MADCE method to obtain full haplotype information for both of the parental cultivars, facilitating in-depth studies on their genomic organisation. The linkage map incorporates 508 segregating loci and represents each of the 28 chromosome pairs of octoploid strawberry, spanning an estimated length of 2050 cM. The sub-genomes are denoted according to their sequence divergence from F. vesca as revealed by marker performance. The map revealed high overall synteny between the sub-genomes, but also revealed two large inversions on LG2C and LG2D, of which the latter was confirmed using a separate mapping population. We discovered interesting breeding features within the parental cultivars by in-depth analysis of our haplotype data. The linkage map-derived homozygosity level of Holiday was similar to the pedigree-derived inbreeding level (33% and 29%, respectively). For Korona we found that the observed homozygosity level was over three times higher than expected from the pedigree (13% versus 3.6%). This could indicate selection pressure on genes that have favourable effects in homozygous states. The level of kinship between Holiday and Korona derived from our linkage map was 2.5 times higher than the pedigree-derived value. This large difference could be evidence of selection pressure enacted by strawberry breeders towards specific haplotypes. The obtained SSR linkage map provides a good base for QTL discovery. It also provides the first biologically relevant basis for the discernment and notation of sub-genomes. For the first time, we revealed genomic rearrangements that were verified in a separate mapping population. We believe that haplotype information will become increasingly important in identifying marker-trait relationships and regions that are under selection pressure within breeding material. Our attempt at providing a biological basis for the discernment of sub-genomes warrants follow-up studies to streamline the naming of the sub-genomes among different octoploid strawberry maps.

Evaluation of identifier field agreement in linked neonatal records.

PubMed

Hall, E S; Marsolo, K; Greenberg, J M

2017-08-01

To better address barriers arising from missing and unreliable identifiers in neonatal medical records, we evaluated agreement and discordance among traditional and non-traditional linkage fields within a linked neonatal data set. The retrospective, descriptive analysis represents infants born from 2013 to 2015. We linked children's hospital neonatal physician billing records to newborn medical records originating from an academic delivery hospital and evaluated rates of agreement, discordance and missingness for a set of 12 identifier field pairs used in the linkage algorithm. We linked 7293 of 7404 physician billing records (98.5%), all of which were deemed valid upon manual review. Linked records contained a mean of 9.1 matching and 1.6 non-matching identifier pairs. Only 4.8% had complete agreement among all 12 identifier pairs. Our approach to selection of linkage variables and data formatting preparatory to linkage have generalizability, which may inform future neonatal and perinatal record linkage efforts.

An autosomal genetic linkage map of the sheep genome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crawford, A.M.; Ede, A.J.; Pierson, C.A.

1995-06-01

We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation full-sib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum numbermore » of informative meioses within the mapping flock was 22. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes. 102 refs., 8 figs., 5 tabs.« less

A framework linkage map of perennial ryegrass based on SSR markers

Treesearch

G.P. Gill; P.L. Wilcox; D.J. Whittaker; R.A. Winz; P. Bickerstaff; Craig E. Echt; J. Kent; M.O. Humphreys; K.M. Elborough; R.C. Gardner

2006-01-01

A moderate-density linkage map for Lolium perenne L. has been constructed based on 376 simple sequence repeat (SSR) markers. Approximately one third ( 124) of the SSR markers were developed from GeneThresher libraries that preferentially select genomic DNA clones from the gene-rich unmethylated portion of the genome. The remaining SSR marker loci...

Project Link-Four: Pre-Vocational Education for Adults through Community Linkages.

ERIC Educational Resources Information Center

Stedman, Deborah S.

The Texas adult performance level (APL) project LINK-FOUR implemented a curriculum based on functional competencies at four sites (Austin, Texarkana, Texas City, and Abilene) and formed linkages with local organizations involved in adult vocational education. The concept on which the project was based was that a set of prevocational skills, plus a…

A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population.

PubMed

Liu, Fan; Arias-Vásquez, Alejandro; Sleegers, Kristel; Aulchenko, Yurii S; Kayser, Manfred; Sanchez-Juan, Pascual; Feng, Bing-Jian; Bertoli-Avella, Aida M; van Swieten, John; Axenovich, Tatiana I; Heutink, Peter; van Broeckhoven, Christine; Oostra, Ben A; van Duijn, Cornelia M

2007-07-01

Alzheimer disease (AD) is the most common cause of dementia. We conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that is conducted in a recently isolated population from the southwestern area of The Netherlands. All patients and their 170 closely related relatives were genotyped using 402 microsatellite markers. Extensive genealogy information was collected, which resulted in an extremely large and complex pedigree of 4,645 members. The pedigree was split into 35 subpedigrees, to reduce the computational burden of linkage analysis. Simulations aiming to evaluate the effect of pedigree splitting on false-positive probabilities showed that a LOD score of 3.64 corresponds to 5% genomewide type I error. Multipoint analysis revealed four significant and one suggestive linkage peaks. The strongest evidence of linkage was found for chromosome 1q21 (heterogeneity LOD [HLOD]=5.20 at marker D1S498). Approximately 30 cM upstream of this locus, we found another peak at 1q25 (HLOD=4.0 at marker D1S218). These two loci are in a previously established linkage region. We also confirmed the AD locus at 10q22-24 (HLOD=4.15 at marker D10S185). There was significant evidence of linkage of AD to chromosome 3q22-24 (HLOD=4.44 at marker D3S1569). For chromosome 11q24-25, there was suggestive evidence of linkage (HLOD=3.29 at marker D11S1320). We next tested for association between cognitive function and 4,173 single-nucleotide polymorphisms in the linked regions in an independent sample consisting of 197 individuals from the GRIP region. After adjusting for multiple testing, we were able to detect significant associations for cognitive function in four of five AD-linked regions, including the new region on chromosome 3q22-24 and regions 1q25, 10q22-24, and 11q25. With use of cognitive function as an endophenotype of AD, our study indicates the that the RGSL2, RALGPS2, and C1orf49 genes are the potential disease-causing genes at 1q25. Our analysis of chromosome 10q22-24 points to the HTR7, MPHOSPH1, and CYP2C cluster. This is the first genomewide screen that showed significant linkage to chromosome 3q23 markers. For this region, our analysis identified the NMNAT3 and CLSTN2 genes. Our findings confirm linkage to chromosome 11q25. We were unable to confirm SORL1; instead, our analysis points to the OPCML and HNT genes.

Discrimination of candidate subgenome-specific loci by linkage map construction with an S1 population of octoploid strawberry (Fragaria × ananassa).

PubMed

Nagano, Soichiro; Shirasawa, Kenta; Hirakawa, Hideki; Maeda, Fumi; Ishikawa, Masami; Isobe, Sachiko N

2017-05-12

The strawberry, Fragaria × ananassa, is an allo-octoploid (2n = 8x = 56) and outcrossing species. Although it is the most widely consumed berry crop in the world, its complex genome structure has hindered its genetic and genomic analysis, and thus discrimination of subgenome-specific loci among the homoeologous chromosomes is needed. In the present study, we identified candidate subgenome-specific single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) loci, and constructed a linkage map using an S 1 mapping population of the cultivar 'Reikou' with an IStraw90 Axiom® SNP array and previously published SSR markers. The 'Reikou' linkage map consisted of 11,574 loci (11,002 SNPs and 572 SSR loci) spanning 2816.5 cM of 31 linkage groups. The 11,574 loci were located on 4738 unique positions (bin) on the linkage map. Of the mapped loci, 8999 (8588 SNPs and 411 SSR loci) showed a 1:2:1 segregation ratio of AA:AB:BB allele, which suggested the possibility of deriving loci from candidate subgenome-specific sequences. In addition, 2575 loci (2414 SNPs and 161 SSR loci) showed a 3:1 segregation of AB:BB allele, indicating they were derived from homoeologous genomic sequences. Comparative analysis of the homoeologous linkage groups revealed differences in genome structure among the subgenomes. Our results suggest that candidate subgenome-specific loci are randomly located across the genomes, and that there are small- to large-scale structural variations among the subgenomes. The mapped SNPs and SSR loci on the linkage map are expected to be seed points for the construction of pseudomolecules in the octoploid strawberry.

A Narrow and Highly Significant Linkage Signal for Severe Bipolar Disorder in the Chromosome 5q33 Region in Latin American Pedigrees

PubMed Central

Jasinska, A.J.; Service, S.; Jawaheer, D.; DeYoung, J.; Levinson, M.; Zhang, Z.; Kremeyer, B.; Muller, H.; Aldana, I.; Garcia, J.; Restrepo, G.; Lopez, C.; Palacio, C.; Duque, C.; Parra, M.; Vega, J.; Ortiz, D.; Bedoya, G.; Mathews, C.; Davanzo, P.; Fournier, E.; Bejarano, J.; Ramirez, M.; Ortiz, C. Araya; Araya, X.; Molina, J.; Sabatti, C.; Reus, V.; Ospina, J.; Macaya, G.; Ruiz-Linares, A.; Freimer, N.B.

2016-01-01

We previously reported linkage of bipolar disorder to 5q33-q34 in families from two closely related population isolates, the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (CO). Here we present follow up results from fine-scale mapping in large CVCR and CO families segregating severe bipolar disorder, BP-I, and in 343 population trios/duos from CVCR and CO. Employing densely spaced SNPs to fine map the prior linkage peak region increases linkage evidence and clarifies the position of the putative BP-I locus. We performed two-point linkage analysis with 1134 SNPs in an approximately 9 Mb region between markers D5S410 and D5S422. Combining pedigrees from CVCR and CO yields a LOD score of 4.9 at SNP rs10035961. Two other SNPs (rs7721142 and rs1422795) within the same 94 kb region also displayed LOD scores greater than 4. This linkage peak coincides with our prior microsatellite results and suggests a narrowed BP-I susceptibility regions in these families. To investigate if the locus implicated in the familial form of BP-I also contributes to disease risk in the population, we followed up the family results with association analysis in duo and trio samples, obtaining signals within 2 Mb of the peak linkage signal in the pedigrees; rs12523547 and rs267015 (P = 0.00004 and 0.00016, respectively) in the CO sample and rs244960 in the CVCR sample and the combined sample, with P = 0.00032 and 0.00016, respectively. It remains unclear whether these association results reflect the same locus contributing to BP susceptibility within the extended pedigrees. PMID:19319892

On computation of p-values in parametric linkage analysis.

PubMed

Kurbasic, Azra; Hössjer, Ola

2004-01-01

Parametric linkage analysis is usually used to find chromosomal regions linked to a disease (phenotype) that is described with a specific genetic model. This is done by investigating the relations between the disease and genetic markers, that is, well-characterized loci of known position with a clear Mendelian mode of inheritance. Assume we have found an interesting region on a chromosome that we suspect is linked to the disease. Then we want to test the hypothesis of no linkage versus the alternative one of linkage. As a measure we use the maximal lod score Z(max). It is well known that the maximal lod score has asymptotically a (2 ln 10)(-1) x (1/2 chi2(0) + 1/2 chi2(1)) distribution under the null hypothesis of no linkage when only one point (one marker) on the chromosome is studied. In this paper, we show, both by simulations and theoretical arguments, that the null hypothesis distribution of Zmax has no simple form when more than one marker is used (multipoint analysis). In fact, the distribution of Zmax depends on the number of families, their structure, the assumed genetic model, marker denseness, and marker informativity. This means that a constant critical limit of Zmax leads to tests associated with different significance levels. Because of the above-mentioned problems, from the statistical point of view the maximal lod score should be supplemented by a p-value when results are reported. Copyright (c) 2004 S. Karger AG, Basel.

Wide-cross whole-genome radiation hybrid mapping of cotton (Gossypium hirsutum L.).

PubMed Central

Gao, Wenxiang; Chen, Z Jeffrey; Yu, John Z; Raska, Dwaine; Kohel, Russell J; Womack, James E; Stelly, David M

2004-01-01

We report the development and characterization of a "wide-cross whole-genome radiation hybrid" (WWRH) panel from cotton (Gossypium hirsutum L.). Chromosomes were segmented by gamma-irradiation of G. hirsutum (n = 26) pollen, and segmented chromosomes were rescued after in vivo fertilization of G. barbadense egg cells (n = 26). A 5-krad gamma-ray WWRH mapping panel (N = 93) was constructed and genotyped at 102 SSR loci. SSR marker retention frequencies were higher than those for animal systems and marker retention patterns were informative. Using the program RHMAP, 52 of 102 SSR markers were mapped into 16 syntenic groups. Linkage group 9 (LG 9) SSR markers BNL0625 and BNL2805 had been colocalized by linkage analysis, but their order was resolved by differential retention among WWRH plants. Two linkage groups, LG 13 and LG 9, were combined into one syntenic group, and the chromosome 1 linkage group marker BNL4053 was reassigned to chromosome 9. Analyses of cytogenetic stocks supported synteny of LG 9 and LG 13 and localized them to the short arm of chromosome 17. They also supported reassignment of marker BNL4053 to the long arm of chromosome 9. A WWRH map of the syntenic group composed of linkage groups 9 and 13 was constructed by maximum-likelihood analysis under the general retention model. The results demonstrate not only the feasibility of WWRH panel construction and mapping, but also complementarity to traditional linkage mapping and cytogenetic methods. PMID:15280245

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

PubMed

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

2008-04-01

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

A randomised controlled trial to compare opt-in and opt-out parental consent for childhood vaccine safety surveillance using data linkage: study protocol.

PubMed

Berry, Jesia G; Ryan, Philip; Braunack-Mayer, Annette J; Duszynski, Katherine M; Xafis, Vicki; Gold, Michael S

2011-01-04

The Vaccine Assessment using Linked Data (VALiD) trial compared opt-in and opt-out parental consent for a population-based childhood vaccine safety surveillance program using data linkage. A subsequent telephone interview of all households enrolled in the trial elicited parental intent regarding the return or non-return of reply forms for opt-in and opt-out consent. This paper describes the rationale for the trial and provides an overview of the design and methods. Single-centre, single-blind, randomised controlled trial (RCT) stratified by firstborn status. Mothers who gave birth at one tertiary South Australian hospital were randomised at six weeks post-partum to receive an opt-in or opt-out reply form, along with information explaining data linkage. The primary outcome at 10 weeks post-partum was parental participation in each arm, as indicated by the respective return or non-return of a reply form (or via telephone or email response). A subsequent telephone interview at 10 weeks post-partum elicited parental intent regarding the return or non-return of the reply form, and attitudes and knowledge about data linkage, vaccine safety, consent preferences and vaccination practices. Enrolment began in July 2009 and 1,129 households were recruited in a three-month period. Analysis has not yet been undertaken. The participation rate and selection bias for each method of consent will be compared when the data are analysed. The VALiD RCT represents the first trial of opt-in versus opt-out consent for a data linkage study that assesses consent preferences and intent compared with actual opting in or opting out behaviour, and socioeconomic factors. The limitations to generalisability are discussed. Australian New Zealand Clinical Trials Registry ACTRN12610000332022.

Genome-wide linkage scan for submaximal exercise heart rate in the HERITAGE family study.

PubMed

Spielmann, Nadine; Leon, Arthur S; Rao, D C; Rice, Treva; Skinner, James S; Rankinen, Tuomo; Bouchard, Claude

2007-12-01

The purpose of this study was to identify regions of the human genome linked to submaximal exercise heart rates in the sedentary state and in response to a standardized 20-wk endurance training program in blacks and whites of the HERITAGE Family Study. A total of 701 polymorphic markers covering the 22 autosomes were used in the genome-wide linkage scan, with 328 sibling pairs from 99 white nuclear families and 102 pairs from 115 black family units. Steady-state heart rates were measured at the relative intensity of 60% maximal oxygen uptake (HR60) and at the absolute intensity of 50 W (HR50). Baseline phenotypes were adjusted for age, sex, and baseline body mass index (BMI) and training responses (posttraining minus baseline, Delta) were adjusted for age, sex, baseline BMI, and baseline value of the phenotype. Two analytic strategies were used, a multipoint variance components and a regression-based multipoint linkage analysis. In whites, promising linkages (LOD > 1.75) were identified on 18q21-q22 for baseline HR50 (LOD = 2.64; P = 0.0002) and DeltaHR60 (LOD = 2.10; P = 0.0009) and on chromosome 2q33.3 for DeltaHR50 (LOD = 2.13; P = 0.0009). In blacks, evidence of promising linkage for baseline HR50 was detected with several markers within the chromosomal region 10q24-q25.3 (peak LOD = 2.43, P = 0.0004 with D10S597). The most promising regions for fine mapping in the HERITAGE Family Study were found on 2q33 for HR50 training response in whites, on 10q25-26 for baseline HR60 in blacks, and on 18q21-22 for both baseline HR50 and DeltaHR60 in whites.

Physiological Linkage in Couples and its Implications for Individual and Interpersonal Functioning: A Literature Review

PubMed Central

Timmons, Adela C.; Margolin, Gayla; Saxbe, Darby E.

2015-01-01

Do partners’ levels of physiological arousal become linked in close relationships? The term “physiological linkage” describes covariation between people in their moment-to-moment physiological states. The current review presents a conceptual framework to guide research on linkage in romantic relationships and discusses the potential implications of being “linked.” Evidence of linkage was found across a broad range of physiological indices and in a variety of contexts, including during laboratory-based conflict and in daily life. Four hypotheses regarding how linkage relates to individual and interpersonal functioning are evaluated: (1) co-activation of the sympathetic nervous system or hypothalamic-pituitary adrenal axis is “bad,” (2) moderate physiological linkage is “just right,” (3) physiological linkage is problematic if the individual or couple is overloaded, and (4) the implications of physiological linkage depend on the emotional context. We found partial support for the first hypothesis and determined that more research is needed to evaluate the remaining hypotheses. Linkage in cortisol was negatively associated with relationship satisfaction; but at the same time, linkage in multiple systems was positively associated with indices of relationship connectedness, such as the amount of time spent together and the ability to identify the emotions of one’s partner. These results suggest that linkage may confer benefits but also may put couples at risk if they become entrenched in patterns of conflict or stress. With research in this area burgeoning in recent years, this review indicates that linkage is a promising construct with applications for interventions targeting individual health and couple functioning. PMID:26147932

Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.

PubMed

Martin, E R; Scott, W K; Nance, M A; Watts, R L; Hubble, J P; Koller, W C; Lyons, K; Pahwa, R; Stern, M B; Colcher, A; Hiner, B C; Jankovic, J; Ondo, W G; Allen, F H; Goetz, C G; Small, G W; Masterman, D; Mastaglia, F; Laing, N G; Stajich, J M; Ribble, R C; Booze, M W; Rogala, A; Hauser, M A; Zhang, F; Gibson, R A; Middleton, L T; Roses, A D; Haines, J L; Scott, B L; Pericak-Vance, M A; Vance, J M

2001-11-14

The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. To investigate whether the tau gene is involved in idiopathic PD. Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. Family-based tests of association, calculated using asymptotic distributions. Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.

Linkage analysis of primary open-angle glaucoma excludes the juvenile glaucoma region on chromosome 1q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wirtz, M.K.; Acott, T.S.; Samples, J.R.

1994-09-01

The gene for one form of juvenile glaucoma has been mapped to chromosome 1q21-q31. This raises the possibility of primary open-angle glaucoma (POAG) also mapping to this region if the same defective gene causes both diseases. To ask this question linkage analysis was performed on a large POAG kindred. Blood samples or skin biopsies were obtained from 40 members of this family. Individuals were diagnosed as having POAG if they met two or more of the following criteria: (1) Visual field defects compatible with glaucoma on automated perimetry; (2) Optic nerve head and/or nerve fiber layer analysis compatible with glaucomatousmore » damage; (3) high intraocular pressures (> 20 mm Hg). Patients were considered glaucoma suspects if they only met one criterion. These individuals were excluded from the analysis. Of the 40 members, seven were diagnosed with POAG; four were termed suspects. The earliest age of onset was 38 years old, while the average age of onset was 65 years old. We performed two-point and multipoint linkage analysis, using five markers which encompass the region 1q21-q31; specifically, D1S194, D1S210, D1S212, D1S191 and LAMB2. Two-point lod scores excluded tight linkage with all markers except D1S212 (maximum lod score of 1.07 at theta = 0.0). In the multipoint analysis, including D1S210-D1S212-LAMB2 and POAG, the entire 11 cM region spanned by these markers was excluded for linkage with POAG; that is, lod scores were < -2.0. In conclusion, POAG in this family does not map to chromosome 1q21-q31 and, thus, they carry a gene that is distinct from the juvenile glaucoma gene.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haines, J.L.; Worster, T.; Ter-Minassian, M.

The loci for juvenile (CLN3) and infantile (CLN1) neuronal ceroid lipofuscinosis (NCL) types have been mapped by genetic linkage analysis to chromosome arms 16p and 1p, respectively. The late-infantile defect CLN2 has not yet been mapped, although linkage analysis with tightly linked markers excludes it from both the JNCL and INCL loci. We have initiated a genome-wide search for the LNCL gene, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it possible to carry out successful linkage analysis in smallmore » nuclear families, such as found in LNCL. Our current collection of LNCL pedigrees includes 19 US families and 11 Costa Rican families. To date, we have completed typing with over 50 markers on chromosomes 2, 9, 13, and 18-22. The results of this analysis formally exclude about 10% of the human genome as the location of the LNCL gene. 14 refs., 3 tabs.« less

Nested association mapping of stem rust resistance in wheat using genotyping by sequencing

USDA-ARS?s Scientific Manuscript database

Nested association mapping is an approach to map trait loci in which families within populations are interconnected by a common parent. By implementing joint-linkage association analysis, this approach is able to map causative loci with higher power and resolution compared to biparental linkage mapp...

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

USDA-ARS?s Scientific Manuscript database

Nested association mapping (NAM) is a novel genetic mating design that combines the advantages of linkage analysis and association mapping. This design provides opportunities to study the inheritance of complex traits, but also requires more advanced statistical methods. In this paper, we present th...

University-Industry Linkages in Developing Countries: Perceived Effect on Innovation

ERIC Educational Resources Information Center

Vaaland, Terje I.; Ishengoma, Esther

2016-01-01

Purpose: The purpose of this paper is to assess the perceptions of both universities and the resource-extractive companies on the influence of university-industry linkages (UILs) on innovation in a developing country. Design/Methodology/Approach: A total of 404 respondents were interviewed. Descriptive analysis and multinomial logistic regression…

Further evidence for the increased power of LOD scores compared with nonparametric methods.

PubMed

Durner, M; Vieland, V J; Greenberg, D A

1999-01-01

In genetic analysis of diseases in which the underlying model is unknown, "model free" methods-such as affected sib pair (ASP) tests-are often preferred over LOD-score methods, although LOD-score methods under the correct or even approximately correct model are more powerful than ASP tests. However, there might be circumstances in which nonparametric methods will outperform LOD-score methods. Recently, Dizier et al. reported that, in some complex two-locus (2L) models, LOD-score methods with segregation analysis-derived parameters had less power to detect linkage than ASP tests. We investigated whether these particular models, in fact, represent a situation that ASP tests are more powerful than LOD scores. We simulated data according to the parameters specified by Dizier et al. and analyzed the data by using a (a) single locus (SL) LOD-score analysis performed twice, under a simple dominant and a recessive mode of inheritance (MOI), (b) ASP methods, and (c) nonparametric linkage (NPL) analysis. We show that SL analysis performed twice and corrected for the type I-error increase due to multiple testing yields almost as much linkage information as does an analysis under the correct 2L model and is more powerful than either the ASP method or the NPL method. We demonstrate that, even for complex genetic models, the most important condition for linkage analysis is that the assumed MOI at the disease locus being tested is approximately correct, not that the inheritance of the disease per se is correctly specified. In the analysis by Dizier et al., segregation analysis led to estimates of dominance parameters that were grossly misspecified for the locus tested in those models in which ASP tests appeared to be more powerful than LOD-score analyses.

Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33. 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dixon, M.J.; Dixon, J.; Houseal, T.

Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCOF1 locus has been localized to chromosome 5q32-33.2. In the present study the authors have used the combined techniques of genetic linkage analysis and fluorescence in situ hybridization (FISH) to more accurately define the TCOF1 critical region. Cosmids IG90 and SPARC, which map to distal 5q, encompass two and one hypervariable microsatellite markers, respectively. The heterozygosity values of these three markers range from .72 to .81. Twenty-two unrelated TCOF1 families have been analyzed for linkage tomore » these markers. There is strong evidence demonstrating linkage to all three markers, the strongest support for positive linkage being provided by haplotyping those markers at the locus encompassed by the cosmid IG90 (Z[sub max]= 19.65; 0 = .010). FISH to metaphase chromosomes and interphase nuclei established that IG90 lies centromeric to SPARC. This information combined with the data generated by genetic linkage analysis demonstrated that the TCOF1 locus is closely flanked proximally by IG90 and distally by SPARC. 30 refs., 2 figs., 4 tabs.« less

Familial isolated hyperparathyroidism is linked to a 1.7 Mb region on chromosome 2p13.3–14

PubMed Central

Warner, J; Nyholt, D R; Busfield, F; Epstein, M; Burgess, J; Stranks, S; Hill, P; Perry‐Keene, D; Learoyd, D; Robinson, B; Teh, B T; Prins, J B; Cardinal, J W

2006-01-01

Bachground Familial isolated hyperparathyroidism (FIHP) is an autosomal dominantly inherited form of primary hyperparathyroidism. Although comprising only about 1% of cases of primary hyperparathyroidism, identification and functional analysis of a causative gene for FIHP is likely to advance our understanding of parathyroid physiology and pathophysiology. Methods A genome‐wide screen of DNA from seven pedigrees with FIHP was undertaken in order to identify a region of genetic linkage with the disorder. Results Multipoint linkage analysis identified a region of suggestive linkage (LOD score 2.68) on chromosome 2. Fine mapping with the addition of three other families revealed significant linkage adjacent to D2S2368 (maximum multipoint LOD score 3.43). Recombination events defined a 1.7 Mb region of linkage between D2S2368 and D2S358 in nine pedigrees. Sequencing of the two most likely candidate genes in this region, however, did not identify a gene for FIHP. Conclusions We conclude that a causative gene for FIHP lies within this interval on chromosome 2. This is a major step towards eventual precise identification of a gene for FIHP, likely to be a key component in the genetic regulation of calcium homeostasis. PMID:16525030

Wood degradation under UV irradiation: A lignin characterization.

PubMed

Cogulet, Antoine; Blanchet, Pierre; Landry, Véronic

2016-05-01

The photodegradation of white spruce by artificial ageing was studied by several techniques: colourimetry, FTIR-ATR and FT-Raman spectroscopy. Samples were exposed at a xenon lamp for 2000h. Two distinct colour changes were found by colourimetric analysis, yellowing and silvering. These colour modifications indicate the formation of chromophoric structures which supports previous FTIR-ATR experiments. The degradation of lignin to generate the first chromophoric group for yellowing and then the appearance of surface layer cellulose. New carbonyl compounds conjugated with double bond at 1615cm(-1) are probably the second chromophoric group. The crystallinity index was also calculated and showed an increase of cellulose crystallinity by prior degradation of amorphous cellulose. The FT-Raman analysis confirms the wood sensitivity to photodegradation but the most remarkable results is the increase of fluorescence as a function of time. In softwood lignin, the compound able to produce fluorescence is a free rotating 5-5' linkage of one biphenyl structure. At native state these linkages are not free rotating, this phenomenon means the release of 5-5' linkage of lignin structure by cleavage of both α carbon linkages (Norrish type I reaction). These data confirm also the photosensitivity of α and β carbon in lignin and the resistance of 5-5' linkages. Copyright © 2016 Elsevier B.V. All rights reserved.

Sexual selection and sex linkage.

PubMed

Kirkpatrick, Mark; Hall, David W

2004-04-01

Some animal groups, such as birds, seem prone to extreme forms of sexual selection. One contributing factor may be sex linkage of genes affecting male displays and female preferences. Here we show that sex linkage can have substantial effects on the genetic correlation between these traits and consequently for Fisher's runaway and the good-genes mechanisms of sexual selection. Under some kinds of sex linkage (e.g. Z-linked preferences), a runaway is more likely than under autosomal inheritance, while under others (e.g., X-linked preferences and autosomal displays), the good-genes mechanism is particularly powerful. These theoretical results suggest empirical tests based on the comparative method.

Drought susceptibility of modern rice varieties: an effect of linkage of drought tolerance with undesirable traits

PubMed Central

Vikram, Prashant; Swamy, B. P. Mallikarjuna; Dixit, Shalabh; Singh, Renu; Singh, Bikram P.; Miro, Berta; Kohli, Ajay; Henry, Amelia; Singh, N. K.; Kumar, Arvind

2015-01-01

Green Revolution (GR) rice varieties are high yielding but typically drought sensitive. This is partly due to the tight linkage between the loci governing plant height and drought tolerance. This linkage is illustrated here through characterization of qDTY1.1, a QTL for grain yield under drought that co-segregates with the GR gene sd1 for semi-dwarf plant height. We report that the loss of the qDTY1.1 allele during the GR was due to its tight linkage in repulsion with the sd1 allele. Other drought-yield QTLs (qDTY) also showed tight linkage with traits rejected in GR varieties. Genetic diversity analysis for 11 different qDTY regions grouped GR varieties separately from traditional drought-tolerant varieties, and showed lower frequency of drought tolerance alleles. The increased understanding and breaking of the linkage between drought tolerance and undesirable traits has led to the development of high-yielding drought-tolerant dwarf lines with positive qDTY alleles and provides new hope for extending the benefits of the GR to drought-prone rice-growing regions. PMID:26458744

Construction of a BAC library and mapping BAC clones to the linkage map of Barramundi, Lates calcarifer.

PubMed

Wang, Chun Ming; Lo, Loong Chueng; Feng, Felicia; Gong, Ping; Li, Jian; Zhu, Ze Yuan; Lin, Grace; Yue, Gen Hua

2008-03-25

Barramundi (Lates calcarifer) is an important farmed marine food fish species. Its first generation linkage map has been applied to map QTL for growth traits. To identify genes located in QTL responsible for specific traits, genomic large insert libraries are of crucial importance. We reported herein a bacterial artificial chromosome (BAC) library and the mapping of BAC clones to the linkage map. This BAC library consisted of 49,152 clones with an average insert size of 98 kb, representing 6.9-fold haploid genome coverage. Screening the library with 24 microsatellites and 15 ESTs/genes demonstrated that the library had good genome coverage. In addition, 62 novel microsatellites each isolated from 62 BAC clones were mapped onto the first generation linkage map. A total of 86 BAC clones were anchored on the linkage map with at least one BAC clone on each linkage group. We have constructed the first BAC library for L. calcarifer and mapped 86 BAC clones to the first generation linkage map. This BAC library and the improved linkage map with 302 DNA markers not only supply an indispensable tool to the integration of physical and linkage maps, the fine mapping of QTL and map based cloning genes located in QTL of commercial importance, but also contribute to comparative genomic studies and eventually whole genome sequencing.

Feasibility of Linking Population-Based Cancer Registries and Cancer Center Biorepositories

PubMed Central

McCusker, Margaret E.; Allen, Mark; Fernandez-Ami, Allyn; Gandour-Edwards, Regina

2012-01-01

Purpose: Biospecimen-based research offers tremendous promise as a way to increase understanding of the molecular epidemiology of cancers. Population-based cancer registries can augment this research by providing more clinical detail and long-term follow-up information than is typically available from biospecimen annotations. In order to demonstrate the feasibility of this concept, we performed a pilot linkage between the California Cancer Registry (CCR) and the University of California, Davis Cancer Center Biorepository (UCD CCB) databases to determine if we could identify patients with records in both databases. Methods: We performed a probabilistic data linkage between 2180 UCD CCB biospecimen records collected during the years 2005–2009 and all CCR records for cancers diagnosed from 1988–2009 based on standard data linkage procedures. Results: The 1040 UCD records with a unique medical record number, tissue site, and pathology date were linked to 3.3 million CCR records. Of these, 844 (81.2%) were identified in both databases. Overall, record matches were highest (100%) for cancers of the cervix and testis/other male genital system organs. For the most common cancers, matches were highest for cancers of the lung and respiratory system (93%), breast (91.7%), and colon and rectum (89.5%), and lower for prostate (72.9%). Conclusions: This pilot linkage demonstrated that information on existing biospecimens from a cancer center biorepository can be linked successfully to cancer registry data. Linkages between existing biorepositories and cancer registries can foster productive collaborations and provide a foundation for virtual biorepository networks to support population-based biospecimen research. PMID:24845042

Initial Reactivity of Linkages and Monomer Rings in Lignin Pyrolysis Revealed by ReaxFF Molecular Dynamics.

PubMed

Zhang, Tingting; Li, Xiaoxia; Guo, Li

2017-10-24

The initial conversion pathways of linkages and their linked monomer units in lignin pyrolysis were investigated comprehensively by ReaxFF MD simulations facilitated by the unique VARxMD for reaction analysis. The simulated molecular model contains 15 920 atoms and was constructed on the basis of Adler's softwood lignin model. The simulations uncover the initial conversion ratio of various linkages and their linked aryl monomers. For linkages and their linked monomer aryl rings of α-O-4, β-O-4 and α-O-4 & β-5, the C α /C β ether bond cracking dominates the initial pathway accounting for at least up to 80% of their consumption. For the linkage of β-β & γ-O-α, both the C α -O ether bond cracking and its linked monomer aryl ring opening are equally important. Ring-opening reactions dominate the initial consumption of other 4-O-5, 5-5, β-1, β-2, and β-5 linkages and their linked monomers. The ether bond cracking of C α -O and C β -O occurs at low temperature, and the aryl ring-opening reactions take place at relatively high temperature. The important intermediates leading to the stable aryl ring opening are the phenoxy radicals, the bridged five-membered and three-membered rings and the bridged six-membered and three-membered rings. In addition, the reactivity of a linkage and its monomer aryl ring may be affected by other linkages. The ether bond cracking of α-O-4 and β-O-4 linkages can activate its neighboring linkage or monomer ring through the formed phenoxy radicals as intermediates. The important intermediates revealed in this article should be of help in deepening the understanding of the controlling mechanism for producing aromatic chemicals from lignin pyrolysis.

Posterior probability of linkage and maximal lod score.

PubMed

Génin, E; Martinez, M; Clerget-Darpoux, F

1995-01-01

To detect linkage between a trait and a marker, Morton (1955) proposed to calculate the lod score z(theta 1) at a given value theta 1 of the recombination fraction. If z(theta 1) reaches +3 then linkage is concluded. However, in practice, lod scores are calculated for different values of the recombination fraction between 0 and 0.5 and the test is based on the maximum value of the lod score Zmax. The impact of this deviation of the test on the probability that in fact linkage does not exist, when linkage was concluded, is documented here. This posterior probability of no linkage can be derived by using Bayes' theorem. It is less than 5% when the lod score at a predetermined theta 1 is used for the test. But, for a Zmax of +3, we showed that it can reach 16.4%. Thus, considering a composite alternative hypothesis instead of a single one decreases the reliability of the test. The reliability decreases rapidly when Zmax is less than +3. Given a Zmax of +2.5, there is a 33% chance that linkage does not exist. Moreover, the posterior probability depends not only on the value of Zmax but also jointly on the family structures and on the genetic model. For a given Zmax, the chance that linkage exists may then vary.

A New Method for Assessing How Sensitivity and Specificity of Linkage Studies Affects Estimation

PubMed Central

Moore, Cecilia L.; Amin, Janaki; Gidding, Heather F.; Law, Matthew G.

2014-01-01

Background While the importance of record linkage is widely recognised, few studies have attempted to quantify how linkage errors may have impacted on their own findings and outcomes. Even where authors of linkage studies have attempted to estimate sensitivity and specificity based on subjects with known status, the effects of false negatives and positives on event rates and estimates of effect are not often described. Methods We present quantification of the effect of sensitivity and specificity of the linkage process on event rates and incidence, as well as the resultant effect on relative risks. Formulae to estimate the true number of events and estimated relative risk adjusted for given linkage sensitivity and specificity are then derived and applied to data from a prisoner mortality study. The implications of false positive and false negative matches are also discussed. Discussion Comparisons of the effect of sensitivity and specificity on incidence and relative risks indicate that it is more important for linkages to be highly specific than sensitive, particularly if true incidence rates are low. We would recommend that, where possible, some quantitative estimates of the sensitivity and specificity of the linkage process be performed, allowing the effect of these quantities on observed results to be assessed. PMID:25068293

Growing and navigating the small world Web by local content

PubMed Central

Menczer, Filippo

2002-01-01

Can we model the scale-free distribution of Web hypertext degree under realistic assumptions about the behavior of page authors? Can a Web crawler efficiently locate an unknown relevant page? These questions are receiving much attention due to their potential impact for understanding the structure of the Web and for building better search engines. Here I investigate the connection between the linkage and content topology of Web pages. The relationship between a text-induced distance metric and a link-based neighborhood probability distribution displays a phase transition between a region where linkage is not determined by content and one where linkage decays according to a power law. This relationship is used to propose a Web growth model that is shown to accurately predict the distribution of Web page degree, based on textual content and assuming only local knowledge of degree for existing pages. A qualitatively similar phase transition is found between linkage and semantic distance, with an exponential decay tail. Both relationships suggest that efficient paths can be discovered by decentralized Web navigation algorithms based on textual and/or categorical cues. PMID:12381792

Growing and navigating the small world Web by local content

NASA Astrophysics Data System (ADS)

Menczer, Filippo

2002-10-01

Can we model the scale-free distribution of Web hypertext degree under realistic assumptions about the behavior of page authors? Can a Web crawler efficiently locate an unknown relevant page? These questions are receiving much attention due to their potential impact for understanding the structure of the Web and for building better search engines. Here I investigate the connection between the linkage and content topology of Web pages. The relationship between a text-induced distance metric and a link-based neighborhood probability distribution displays a phase transition between a region where linkage is not determined by content and one where linkage decays according to a power law. This relationship is used to propose a Web growth model that is shown to accurately predict the distribution of Web page degree, based on textual content and assuming only local knowledge of degree for existing pages. A qualitatively similar phase transition is found between linkage and semantic distance, with an exponential decay tail. Both relationships suggest that efficient paths can be discovered by decentralized Web navigation algorithms based on textual and/or categorical cues.

Growing and navigating the small world Web by local content.

PubMed

Menczer, Filippo

2002-10-29

Can we model the scale-free distribution of Web hypertext degree under realistic assumptions about the behavior of page authors? Can a Web crawler efficiently locate an unknown relevant page? These questions are receiving much attention due to their potential impact for understanding the structure of the Web and for building better search engines. Here I investigate the connection between the linkage and content topology of Web pages. The relationship between a text-induced distance metric and a link-based neighborhood probability distribution displays a phase transition between a region where linkage is not determined by content and one where linkage decays according to a power law. This relationship is used to propose a Web growth model that is shown to accurately predict the distribution of Web page degree, based on textual content and assuming only local knowledge of degree for existing pages. A qualitatively similar phase transition is found between linkage and semantic distance, with an exponential decay tail. Both relationships suggest that efficient paths can be discovered by decentralized Web navigation algorithms based on textual and/or categorical cues.

A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations.

PubMed

Kling, Daniel; Tillmar, Andreas; Egeland, Thore; Mostad, Petter

2015-09-01

Several applications necessitate an unbiased determination of relatedness, be it in linkage or association studies or in a forensic setting. An appropriate model to compute the joint probability of some genetic data for a set of persons given some hypothesis about the pedigree structure is then required. The increasing number of markers available through high-density SNP microarray typing and NGS technologies intensifies the demand, where using a large number of markers may lead to biased results due to strong dependencies between closely located loci, both within pedigrees (linkage) and in the population (allelic association or linkage disequilibrium (LD)). We present a new general model, based on a Markov chain for inheritance patterns and another Markov chain for founder allele patterns, the latter allowing us to account for LD. We also demonstrate a specific implementation for X chromosomal markers that allows for computation of likelihoods based on hypotheses of alleged relationships and genetic marker data. The algorithm can simultaneously account for linkage, LD, and mutations. We demonstrate its feasibility using simulated examples. The algorithm is implemented in the software FamLinkX, providing a user-friendly GUI for Windows systems (FamLinkX, as well as further usage instructions, is freely available at www.famlink.se ). Our software provides the necessary means to solve cases where no previous implementation exists. In addition, the software has the possibility to perform simulations in order to further study the impact of linkage and LD on computed likelihoods for an arbitrary set of markers.

Effective interventions to improve young adults' linkage to HIV care in Sub-Saharan Africa: a systematic review.

PubMed

Mavegam, Bertille Octavie; Pharr, Jennifer R; Cruz, Patricia; Ezeanolue, Echezona E

2017-10-01

HIV/AIDS remains a major public health problem despite the efforts to prevent and decrease its spread. Sub-Saharan Africa (SSA) represents 70% of the global number of people living with HIV and 73% of all HIV/AIDS-related deaths. Young adults age 15-24 years are disproportionately impacted by HIV/AIDS in SSA with 34% of people living with HIV (PLWHIV) and 37% of newly diagnosed individuals being in this age group. It is important that PLWHIV be linked to care to facilitate antiretroviral therapy (ART) initiation and limit the spread of infection. We conducted a systematic literature review to identify effective interventions designed to improve linkage to care among HIV-infected young adults in SSA. One hundred and forty-six titles and abstracts were screened, 28 full-texts were reviewed, and 6 articles met the inclusion and exclusion criteria. Home-based HIV counseling and testing, home-based HIV self-testing, and mobile HIV counseling and testing followed by proper referral of HIV-positive patients to HIV care were effective for improving linkage of young adults to care. Other factors such as referral forms, transportation allowance, home initiation of HIV care, and volunteer escort to the HIV treatment clinic were effective in reducing time to linkage to care. There is a vast need for research and interventions that target HIV-positive young adults in SSA which aim to improve their linkage and access to HIV care. The results of this study illustrate effective interventions in improving linkage to care and reducing time to linkage to care of young adults in SSA.

Allelic loss and linkage studies in prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, D.R.; Bale, A.E.; Lytton, B.

1994-09-01

Prostate cancer is the most common malignancy in U.S. males. Many examples of familial aggregation have been reported, and segregration analysis suggests that an autosomal dominant gene with a penetrance of 88% by age 85 accounts for 9% of all cases. Because many dominant cancer predisposition syndromes are related to germline mutations in tumor suppressor genes, we analyzed a series of sporadic and hereditary tumors for allelic loss. High grade sporadic, paraffin-embedded, primary prostate tumors were obtained from the archival collection in the Department of Pathology at Yale and hereditary tumors from three families were obtained by an advertisement inmore » the New York Times and from referrals by urologists. PCR analysis showed loss in 4/7 informative sporadic prostate tumors with NEFL (8p21), in 8/22 informative tumors with D10S169 (10q26-qter), in 2/8 informative tumors with D10S108 (10q) and in 4/23 informative tumors with D10S89 (10p) in agreement with previous studies. PYGM on chromosome 11 and D9S127 on chromosome 9 showed no loss. Linkage analysis with NEFL in 3 prostate cancer families gave strongly negative results for close linkage (Z=-2.1 at {theta}=0.01) but LOD scores were very dependent on parameters, e.g. gene frequency, phenocopy rate, and penetrance. Linkage analysis with chromosome 10 markers and systematic analysis of the genome for other area of allelic loss are underway.« less

Genetic dissection of MHC-associated susceptibility to Lepeophtheirus salmonis in Atlantic salmon

PubMed Central

Gharbi, Karim; Glover, Kevin A; Stone, Louise C; MacDonald, Elizabeth S; Matthews, Louise; Grimholt, Unni; Stear, Michael J

2009-01-01

Background Genetic variation has been shown to play a significant role in determining susceptibility to the salmon louse, Lepeophtheirus salmonis. However, the mechanisms involved in differential response to infection remain poorly understood. Recent findings in Atlantic salmon (Salmo salar) have provided evidence for a potential link between marker variation at the major histocompatibility complex (MHC) and differences in lice abundance among infected siblings, suggesting that MHC genes can modulate susceptibility to the parasite. In this study, we used quantitative trait locus (QTL) analysis to test the effect of genomic regions linked to MHC class I and II on linkage groups (LG) 15 and 6, respectively. Results Significant QTL effects were detected on both LG 6 and LG 15 in sire-based analysis but the QTL regions remained unresolved due to a lack of recombination between markers. In dam-based analysis, a significant QTL was identified on LG 6, which accounted for 12.9% of within-family variance in lice abundance. However, the QTL was located at the opposite end of DAA, with no significant overlap with the MHC class II region. Interestingly, QTL modelling also revealed evidence of sex-linked differences in lice abundance, indicating that males and females may have different susceptibility to infection. Conclusion Overall, QTL analysis provided relatively weak support for a proximal effect of classical MHC regions on lice abundance, which can partly be explained by linkage to other genes controlling susceptibility to L. salmonis on the same chromosome. PMID:19397823

Video-conferencing Telehealth Linkage attempts to Schools to Facilitate Mental Health Consultation.

PubMed

McLennan, John D

2018-04-01

Telehealth to schools may be a strategic approach to expand child mental health service delivery, however, there are only a few published examples. This report describes video-conferencing telehealth linkage attempts to schools to facilitate mental health consultation. A series of synchronous video-conferencing linkage strategies were attempted to connect a mental health consultation service to multiple schools in a Canadian setting. Consultation to support the implementation of the Daily Report Card, for students with attentional and behavioural problems, was the core content of this pilot linkage attempt. Synchronous video conference consultations were successfully delivered to six elementary schools across three school districts. Two of three linkage strategies were functional. One used existing health centre-based telehealth units to connect to school-based dedicated tablets with a video collaboration app and reliance on existing school Wi-Fi. A second used existing laptops in both the health and school system linked through a communication platform. A third connection, using 3G/4G hotspots to obviate the need to access school Wi-Fi, was deemed too expensive in this setting. The potential to use existing computer hardware to connect mental health providers and schools could facilitate scale-up. However, it is unknown whether mental health systems and school sectors will invest in such linkages and reorganize core mental health services to be delivered in this way.

Facilitators and Barriers to Linkage to HIV Care among Female Sex Workers Receiving HIV Testing Services at a Community-Based Organization in Periurban Uganda: A Qualitative Study

PubMed Central

Kintu, Betty N.

2016-01-01

Introduction. While four in ten female sex workers (FSWs) in sub-Saharan Africa are infected with HIV, only a small proportion is enrolled in HIV care. We explored facilitators and barriers to linkage to HIV care among FSWs receiving HIV testing services at a community-based organization in periurban Uganda. Methods. The cross-sectional qualitative study was conducted among 28 HIV positive FSWs from May to July 2014. Key informant interviews were conducted with five project staff and eleven peer educators. Data were collected on facilitators for and barriers to linkage to HIV care and manually analyzed following a thematic framework approach. Results. Facilitators for linkage to HIV care included the perceived good quality of health services with same-day results and immediate initiation of treatment, community peer support systems, individual's need to remain healthy, and having alternative sources of income. Linkage barriers included perceived stigma, fear to be seen at outreach HIV clinics, fear and myths about antiretroviral therapy, lack of time to attend clinic, and financial constraints. Conclusion. Linkage to HIV care among FSWs is influenced by good quality friendly services and peer support. HIV service delivery programs for FSWs should focus on enhancing these and dealing with barriers stemming from stigma and misinformation. PMID:27493826

A ddRAD Based Linkage Map of the Cultivated Strawberry, Fragaria xananassa

PubMed Central

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. PMID:26398886

Linkage analysis with chromosome 9 markers in hereditary essential tremor.

PubMed

Conway, D; Bain, P G; Warner, T T; Davis, M B; Findley, L J; Thompson, P D; Marsden, C D; Harding, A E

1993-07-01

Hereditary essential tremor (ET) is an autosomal dominant disorder with variable expression and reduced penetrance. A tremor indistinguishable from ET may be observed in patients with autosomal dominant idiopathic torsion dystonia (ITD), in which the disease locus has been mapped to 9q32-34 in some kindreds, tightly linked to the argininosuccinate synthetase (ASS) locus. We performed linkage analysis in 15 families with ET containing 60 definitely affected individuals, using dinucleotide repeat polymorphisms at the ASS locus and the Abelson locus (ABL). Cumulative lod scores were -19.5 for ASS and -10.8 for ABL at a recombination fraction of 0.01, and tight linkage to ASS was excluded individually in 11 of the families. These data indicate that the ET gene is not allelic to that causing ITD.

Genetic Diversity, Population Structure, and Linkage Disequilibrium in Bread Wheat (Triticum aestivum L.).

PubMed

Tascioglu, Tulin; Metin, Ozge Karakas; Aydin, Yildiz; Sakiroglu, Muhammet; Akan, Kadir; Uncuoglu, Ahu Altinkut

2016-08-01

Bread wheat (Triticum aestivum L.) gene pool was analyzed with 117 microsatellite markers scattered throughout A, B, and D genomes. Ninety microsatellite markers were giving 1620 polymorphic alleles in 55 different bread wheat genotypes. These genotypes were found to be divided into three subgroups based on Bayesian model and Principal component analysis. The highest polymorphism information content value for the markers resides on A genome was estimated for wmc262 marker located on 4A chromosome with the polymorphism information content value of 0.960. The highest polymorphism information content value (0.954) among the markers known to be located on B genome was realized for wmc44 marker located on 1B chromosome. The highest polymorphism information content value for the markers specific to D genome was found in gwm174 marker located on 5D chromosome with the polymorphism information content value of 0.948. The presence of linkage disequilibrium between 81 pairwise SSR markers reside on the same chromosome was tested and very limited linkage disequilibrium was observed. The results confirmed that the most distant genotype pairs were as follows Ceyhan-99-Behoth 6, Gerek 79-Douma 40989, and Karahan-99-Douma 48114.

Gene mapping study for constitutive skin color in an isolated Mongolian population.

PubMed

Paik, Seung Hwan; Kim, Hyun-Jin; Son, Ho-Young; Lee, Seungbok; Im, Sun-Wha; Ju, Young Seok; Yeon, Je Ho; Jo, Seong Jin; Eun, Hee Chul; Seo, Jeong-Sun; Kwon, Oh Sang; Kim, Jong-Il

2012-03-31

To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In addition, we also found other candidate regions on 17q23.2, 6q25.1, and 13q33.2 (LOD ≥ 2). Family-based association tests on these regions with suggestive linkage peaks revealed ten and two significant single nucleotide polymorphisms (SNPs) on the linkage regions of chromosome 11 and 17, respectively. We were able to discover four possible candidate genes that would be implicated to regulate human skin color: ETS1, UBASH3B, ASAM, and CLTC.

Genome-Wide Association Mapping of Acid Soil Resistance in Barley (Hordeum vulgare L.)

PubMed Central

Zhou, Gaofeng; Broughton, Sue; Zhang, Xiao-Qi; Ma, Yanling; Zhou, Meixue; Li, Chengdao

2016-01-01

Genome-wide association studies (GWAS) based on linkage disequilibrium (LD) have been used to detect QTLs underlying complex traits in major crops. In this study, we collected 218 barley (Hordeum vulgare L.) lines including wild barley and cultivated barley from China, Canada, Australia, and Europe. A total of 408 polymorphic markers were used for population structure and LD analysis. GWAS for acid soil resistance were performed on the population using a general linkage model (GLM) and a mixed linkage model (MLM), respectively. A total of 22 QTLs (quantitative trait loci) were detected with the GLM and MLM analyses. Two QTLs, close to markers bPb-1959 (133.1 cM) and bPb-8013 (86.7 cM), localized on chromosome 1H and 4H respectively, were consistently detected in two different trials with both the GLM and MLM analyses. Furthermore, bPb-8013, the closest marker to the major Al3+ resistance gene HvAACT1 in barley, was identified to be QTL5. The QTLs could be used in marker-assisted selection to identify and pyramid different loci for improved acid soil resistance in barley. PMID:27064793

Gene mapping study for constitutive skin color in an isolated Mongolian population

PubMed Central

Paik, Seung Hwan; Kim, Hyun-Jin; Son, Ho-Young; Lee, Seungbok; Im, Sun-Wha; Ju, Young Seok; Yeon, Je Ho; Jo, Seong Jin; Eun, Hee Chul; Seo, Jeong-Sun

2012-01-01

To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In addition, we also found other candidate regions on 17q23.2, 6q25.1, and 13q33.2 (LOD ≥ 2). Family-based association tests on these regions with suggestive linkage peaks revealed ten and two significant single nucleotide polymorphisms (SNPs) on the linkage regions of chromosome 11 and 17, respectively. We were able to discover four possible candidate genes that would be implicated to regulate human skin color: ETS1, UBASH3B, ASAM, and CLTC. PMID:22198297

The score statistic of the LD-lod analysis: detecting linkage adaptive to linkage disequilibrium.

PubMed

Huang, J; Jiang, Y

2001-01-01

We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers. Copyright 2001 S. Karger AG, Basel

Predicting the number and sizes of IBD regions among family members and evaluating the family size requirement for linkage studies.

PubMed

Yang, Wanling; Wang, Zhanyong; Wang, Lusheng; Sham, Pak-Chung; Huang, Peng; Lau, Yu Lung

2008-12-01

With genotyping of high-density single nucleotide polymorphisms (SNPs) replacing that of microsatellite markers in linkage studies, it becomes possible to accurately determine the genomic regions shared identity by descent (IBD) by family members. In addition to evaluating the likelihood of linkage for a region with the underlining disease (the LOD score approach), an appropriate question to ask is what would be the expected number and sizes of IBD regions among the affecteds, as there could be more than one region reaching the maximum achievable LOD score for a given family. Here, we introduce a computer program to allow the prediction of the total number of IBD regions among family members and their sizes. Reversely, it can be used to predict the portion of the genome that can be excluded from consideration according to the family size and user-defined inheritance mode and penetrance. Such information has implications on the feasibility of conducting linkage analysis on a given family of certain size and structure or on a few small families when interfamily homogeneity can be assumed. It can also help determine the most relevant members to be genotyped for such a study. Simulation results showed that the IBD regions containing true mutations are usually larger than regions IBD due to random chance. We have made use of this feature in our program to allow evaluation of the identified IBD regions based on Bayesian probability calculation and simulation results.

Monte Carlo simulations on marker grouping and ordering.

PubMed

Wu, J; Jenkins, J; Zhu, J; McCarty, J; Watson, C

2003-08-01

Four global algorithms, maximum likelihood (ML), sum of adjacent LOD score (SALOD), sum of adjacent recombinant fractions (SARF) and product of adjacent recombinant fraction (PARF), and one approximation algorithm, seriation (SER), were used to compare the marker ordering efficiencies for correctly given linkage groups based on doubled haploid (DH) populations. The Monte Carlo simulation results indicated the marker ordering powers for the five methods were almost identical. High correlation coefficients were greater than 0.99 between grouping power and ordering power, indicating that all these methods for marker ordering were reliable. Therefore, the main problem for linkage analysis was how to improve the grouping power. Since the SER approach provided the advantage of speed without losing ordering power, this approach was used for detailed simulations. For more generality, multiple linkage groups were employed, and population size, linkage cutoff criterion, marker spacing pattern (even or uneven), and marker spacing distance (close or loose) were considered for obtaining acceptable grouping powers. Simulation results indicated that the grouping power was related to population size, marker spacing distance, and cutoff criterion. Generally, a large population size provided higher grouping power than small population size, and closely linked markers provided higher grouping power than loosely linked markers. The cutoff criterion range for achieving acceptable grouping power and ordering power differed for varying cases; however, combining all situations in this study, a cutoff criterion ranging from 50 cM to 60 cM was recommended for achieving acceptable grouping power and ordering power for different cases.

Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q.

PubMed

Sankila, E M; Pakarinen, L; Kääriäinen, H; Aittomäki, K; Karjalainen, S; Sistonen, P; de la Chapelle, A

1995-01-01

Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to severe, and the vestibular function is normal. Progressive pigmentary retinopathy (PPR) is present in both types. A third type (USH3) differing from USH2 by the progressive nature of its hearing loss has been suggested. USH3 has previously been estimated to comprise 2% of all USH. However, based on clinical criteria, in Finland 42% of USH patients have progressive hearing loss suggesting enrichment of an USH3 gene. We excluded the four previously mapped USH regions as the site of the USH3 disease locus. Systematic search for USH3 by genetic linkage analyses in 10 multiple affected families using polymorphic microsatellite markers revealed significant linkage with markers mapping to chromosome 3q. Pairwise lod scores at zero recombination distance were 7.87 for D3S1308, and 11.29 for D3S1299, incorporating the observed linkage disequilibrium. Conventional multipoint linkage analysis gave a maximum lod score of 9.88 at D3S1299 assigning USH3 to the 5 cM interval between markers D3S1555 and D3S1279 in 3q21-25.(ABSTRACT TRUNCATED AT 250 WORDS)

Data Linkage: A powerful research tool with potential problems

PubMed Central

2010-01-01

Background Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes. Methods A narrative review, using structured search methods was undertaken. Key words "data linkage" and Mesh term "medical record linkage" were applied to Medline, EMBASE and CINAHL databases between 1991 and 2007. Abstract inclusion criteria were; the article attempted an empirical evaluation of methodological issues relating to data linkage and reported on patient characteristics, the study design included analysis of matched versus unmatched records, and the report was in English. Included articles were grouped thematically according to patient characteristics that were compared between matched and unmatched records. Results The search identified 1810 articles of which 33 (1.8%) met inclusion criteria. There was marked heterogeneity in study methods and factors investigated. Characteristics that were unevenly distributed among matched and unmatched records were; age (72% of studies), sex (50% of studies), race (64% of studies), geographical/hospital site (93% of studies), socio-economic status (82% of studies) and health status (72% of studies). Conclusion A number of relevant patient or population factors may be associated with incomplete data linkage resulting in systematic bias in reported clinical outcomes. Readers should consider these factors in interpreting the reported results of data linkage studies. PMID:21176171

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

PubMed Central

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

A population-based study of familial Alzheimer disease: linkage to chromosomes 14, 19, and 21.

PubMed

van Duijn, C M; Hendriks, L; Farrer, L A; Backhovens, H; Cruts, M; Wehnert, A; Hofman, A; Van Broeckhoven, C

1994-10-01

Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was at or before age 65 years, the mean age at onset was after age 65 years in four families (referred to as "LOAD"). Among the six families with early-onset AD (referred to as "EOAD," i.e., mean age of onset of AD of relatives was at or before age 65 years), conclusive linkage to 14q24.3 was found in one family with a very early onset (around 47 years), while linkage to the same region was excluded in two other families. For the LOAD families, predominantly negative lod scores were obtained, and the overall lod score excluded linkage to chromosome 14. The results with markers on chromosome 19 and chromosome 21 were not conclusive for EOAD and LOAD. The findings of our study confirm genetic heterogeneity within familial EOAD.

Nested association mapping for dissecting complex traits using Peanut 58K SNP array

USDA-ARS?s Scientific Manuscript database

Genome-wide association studies (GWAS) and linkage mapping have been the two most predominant strategies to dissect complex traits, but are limited by the occurrence of false positives reported for GWAS, and low resolution in the case of linkage analysis. This has led to the development of a joint a...

Markov chain Monte Carlo linkage analysis: effect of bin width on the probability of linkage.

PubMed

Slager, S L; Juo, S H; Durner, M; Hodge, S E

2001-01-01

We analyzed part of the Genetic Analysis Workshop (GAW) 12 simulated data using Monte Carlo Markov chain (MCMC) methods that are implemented in the computer program Loki. The MCMC method reports the "probability of linkage" (PL) across the chromosomal regions of interest. The point of maximum PL can then be taken as a "location estimate" for the location of the quantitative trait locus (QTL). However, Loki does not provide a formal statistical test of linkage. In this paper, we explore how the bin width used in the calculations affects the max PL and the location estimate. We analyzed age at onset (AO) and quantitative trait number 5, Q5, from 26 replicates of the general simulated data in one region where we knew a major gene, MG5, is located. For each trait, we found the max PL and the corresponding location estimate, using four different bin widths. We found that bin width, as expected, does affect the max PL and the location estimate, and we recommend that users of Loki explore how their results vary with different bin widths.

Religious Attendance and Physiological Problems in Late Life.

PubMed

Das, Aniruddha; Nairn, Stephanie

2016-03-01

This study queried linkages of older adults' religious attendance with their physiological health. Data were from the 2005-2006 National Social Life, Health, and Aging Project, nationally representative of U.S. adults aged 57-85 years. Analyses examined associations of religious attendance with biological states, potential gender variations in these linkages, and attenuation by this factor of health effects of spousal loss. Religious attendance was negatively associated with a system of physiological issues, consistent with mitigation of multisystemic "weathering." Linkages were relatively uniform with inflammatory and cardiovascular but not metabolic states and were not significantly different for women than men. Effects of spousal loss on the 2 former subsystems were attenuated by regular religious attendance-in combined-gender analysis and among women, but not men. Religious attendance may buffer older adults from physiological problems and the health effects of life events such as spousal loss. More intensive analysis is needed to explain differential linkages with specific biological subsystems. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A visual interface to computer programs for linkage analysis.

PubMed

Chapman, C J

1990-06-01

This paper describes a visual approach to the input of information about human families into computer data bases, making use of the GEM graphic interface on the Atari ST. Similar approaches could be used on the Apple Macintosh or on the IBM PC AT (to which it has been transferred). For occasional users of pedigree analysis programs, this approach has considerable advantages in ease of use and accessibility. An example of such use might be the analysis of risk in families with Huntington disease using linked RFLPs. However, graphic interfaces do make much greater demands on the programmers of these systems.

Sociocultural Meanings of Nanotechnology: Research Methodologies

NASA Astrophysics Data System (ADS)

Bainbridge, William Sims

2004-06-01

This article identifies six social-science research methodologies that will be useful for charting the sociocultural meaning of nanotechnology: web-based questionnaires, vignette experiments, analysis of web linkages, recommender systems, quantitative content analysis, and qualitative textual analysis. Data from a range of sources are used to illustrate how the methods can delineate the intellectual content and institutional structure of the emerging nanotechnology culture. Such methods will make it possible in future to test hypotheses such as that there are two competing definitions of nanotechnology - the technical-scientific and the science-fiction - that are influencing public perceptions by different routes and in different directions.

Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases.

PubMed

Abreu, P C; Greenberg, D A; Hodge, S E

1999-09-01

Several methods have been proposed for linkage analysis of complex traits with unknown mode of inheritance. These methods include the LOD score maximized over disease models (MMLS) and the "nonparametric" linkage (NPL) statistic. In previous work, we evaluated the increase of type I error when maximizing over two or more genetic models, and we compared the power of MMLS to detect linkage, in a number of complex modes of inheritance, with analysis assuming the true model. In the present study, we compare MMLS and NPL directly. We simulated 100 data sets with 20 families each, using 26 generating models: (1) 4 intermediate models (penetrance of heterozygote between that of the two homozygotes); (2) 6 two-locus additive models; and (3) 16 two-locus heterogeneity models (admixture alpha = 1.0,.7,.5, and.3; alpha = 1.0 replicates simple Mendelian models). For LOD scores, we assumed dominant and recessive inheritance with 50% penetrance. We took the higher of the two maximum LOD scores and subtracted 0.3 to correct for multiple tests (MMLS-C). We compared expected maximum LOD scores and power, using MMLS-C and NPL as well as the true model. Since NPL uses only the affected family members, we also performed an affecteds-only analysis using MMLS-C. The MMLS-C was both uniformly more powerful than NPL for most cases we examined, except when linkage information was low, and close to the results for the true model under locus heterogeneity. We still found better power for the MMLS-C compared with NPL in affecteds-only analysis. The results show that use of two simple modes of inheritance at a fixed penetrance can have more power than NPL when the trait mode of inheritance is complex and when there is heterogeneity in the data set.

Genome-wide Linkage Analysis for Identifying Quantitative Trait Loci Involved in the Regulation of Lipoprotein a (Lpa) Levels

PubMed Central

López, Sonia; Buil, Alfonso; Ordoñez, Jordi; Souto, Juan Carlos; Almasy, Laura; Lathrop, Mark; Blangero, John; Blanco-Vaca, Francisco; Fontcuberta, Jordi; Soria, José Manuel

2009-01-01

Lipoprotein Lp(a) levels are highly heritable and are associated with cardiovascular risk. We performed a genome-wide linkage analysis to delineate the genomic regions that influence the concentration of Lp(a) in families from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project. Lp(a) levels were measured in 387 individuals belonging to 21 extended Spanish families. A total of 485 DNA microsatellite markers were genotyped to provide a 7.1 cM genetic map. A variance component linkage method was used to evaluate linkage and to detect quantitative trait loci (QTLs). The main QTL that showed strong evidence of linkage with Lp(a) levels was located at the structural gene for apo(a) on Chromosome 6 (LOD score=13.8). Interestingly, another QTL influencing Lp(a) concentration was located on Chromosome 2 with a LOD score of 2.01. This region contains several candidate genes. One of them is the tissue factor pathway inhibitor (TFPI), which has antithrombotic action and also has the ability to bind lipoproteins. However, quantitative trait association analyses performed with 12 SNPs in TFPI gene revealed no association with Lp(a) levels. Our study confirms previous results on the genetic basis of Lp(a) levels. In addition, we report a new QTL on Chromosome 2 involved in the quantitative variation of Lp(a). These data should serve as the basis for further detection of candidate genes and to elucidate the relationship between the concentration of Lp(a) and cardiovascular risk. PMID:18560444

Patterns of linkage disequilibrium at PARK16 may explain variances in genetic association studies.

PubMed

Li, Huihua; Teo, Yik-Ying; Tan, Eng-King

2015-09-01

Reproducing genomewide association studies findings in different populations is challenging, because the reproducibility fundamentally relies on the similar patterns of linkage disequilibrium between the unknown causal variants and the genotyped single-nucleotide polymorphisms (SNPs). The PARK16 locus was reported to alter the risk of Parkinson's disease (PD) in genomewide association studies in Japanese and Caucasians. We evaluated the regional linkage disequilibrium pattern at PARK16 locus in Caucasians, Japanese, and Chinese from HapMap and Chinese, Malays, and Indians from the Singapore Genome Variation Project, using the traditional heatmaps and targeted analysis of PARK16 gene via Monte Carlo simulation through varLD scores of these ethnic groups. One hundred SNPs in Caucasians, 95 SNPs in Chinese, 78 SNPs in Japanese from HapMap, 86 SNPs in Chinese, 99 SNPs in Indians, and 97 SNPs in Malays from the Singapore Genome Variation Project were included. Our targeted analysis showed that the linkage disequilibrium pattern of SNPs close to rs947211 was similar in Caucasians and Asians, including Chinese, Japanese, and Malay (all P > 0.0001), whereas different linkage disequilibrium patterns around rs823128, rs823156, and rs708730 were found between Caucasians and these Asian groups (all P < 0.0001). Our study suggests a higher chance to detect the association between rs947211 and PD in Chinese, Malay, and other Caucasian groups because of the similar linkage disequilibrium pattern around rs947211. The associations between rs823128/rs823156/rs708730 and PD are more likely to be replicated in Chinese and Malay populations. © 2015 International Parkinson and Movement Disorder Society.

Analysis of quantitative lipid traits in the genetics of NIDDM (GENNID) study.

PubMed

Malhotra, Alka; Wolford, Johanna K

2005-10-01

Coronary heart disease (CHD) is the leading cause of death among individuals with type 2 diabetes. Dyslipidemia contributes significantly to CHD in diabetic patients, in whom lipid abnormalities include hypertriglyceridemia, low HDL cholesterol, and increased levels of small, dense LDL particles. To identify genes for lipid-related traits, we performed genome-wide linkage analyses for levels of triglycerides and HDL, LDL, and total cholesterol in Caucasian, Hispanic, and African-American families from the Genetics of NIDDM (GENNID) study. Most lipid traits showed significant estimates of heritability (P < 0.001) with the exception of triglycerides and the triglyceride/HDL ratio in African Americans. Variance components analysis identified linkage on chromosome 3p12.1-3q13.31 for the triglyceride/HDL ratio (logarithm of odds [LOD] = 3.36) and triglyceride (LOD = 3.27) in Caucasian families. Statistically significant evidence for linkage was identified for the triglyceride/HDL ratio (LOD = 2.45) on 11p in Hispanic families in a region that showed suggestive evidence for linkage (LOD = 2.26) for triglycerides in this population. In African Americans, the strongest evidence for linkage (LOD = 2.26) was found on 19p13.2-19q13.42 for total cholesterol. Our findings provide strong support for previous reports of linkage for lipid-related traits, suggesting the presence of genes on 3p12.1-3q13.31, 11p15.4-11p11.3, and 19p13.2-19q13.42 that may influence traits underlying lipid abnormalities associated with type 2 diabetes.

Genetic counseling in Usher syndrome: linkage and mutational analysis of 10 Colombian families.

PubMed

Tamayo, M L; Lopez, G; Gelvez, N; Medina, D; Kimberling, W J; Rodríguez, V; Tamayo, G E; Bernal, J E

2008-01-01

Usher Syndrome (US), an autosomal recessive disease, is characterized by retinitis pigmentosa (RP), vestibular dysfunction, and congenital sensorineural deafness. There are three recognized clinical types of the disorder. In order to improve genetic counseling for affected families, we conducted linkage analysis and DNA sequencing in 10 Colombian families with confirmed diagnosis of US (4 type I and 6 type II). Seventy-five percent of the US1 families showed linkage to locus USH1B, while the remaining 25% showed linkage to loci USH1B and USH1C. Among families showing linkage to USH1B we found two different mutations in the MYO7A gene: IVS42-26insTTGAG in exon 43 (heterozygous state) and R634X (CGA-TGA) in exon 16 (homozygous state). All six US2 families showed linkage to locus USH2A. Of them, 4 had c.2299delG mutation (1 homozygote state and 3 heterozygous); in the remaining 2 we did not identify any pathologic DNA variant. USH2A individuals with a 2299delG mutation presented a typical and homogeneous retinal phenotype with bilateral severe hearing loss, except for one individual with a heterozygous 2299delG mutation, whose hearing loss was asymmetric, but more profound than in the other cases. The study of these families adds to the genotype-phenotype characterization of the different types and subtypes of US and facilitates genetic counseling in these families. We would like to emphasize the need to perform DNA studies as a prerequisite for genetic counseling in affected families.

Evaluation of record linkage of two large administrative databases in a middle income country: stillbirths and notifications of dengue during pregnancy in Brazil.

PubMed

Paixão, Enny S; Harron, Katie; Andrade, Kleydson; Teixeira, Maria Glória; Fiaccone, Rosemeire L; Costa, Maria da Conceição N; Rodrigues, Laura C

2017-07-17

Due to the increasing availability of individual-level information across different electronic datasets, record linkage has become an efficient and important research tool. High quality linkage is essential for producing robust results. The objective of this study was to describe the process of preparing and linking national Brazilian datasets, and to compare the accuracy of different linkage methods for assessing the risk of stillbirth due to dengue in pregnancy. We linked mothers and stillbirths in two routinely collected datasets from Brazil for 2009-2010: for dengue in pregnancy, notifications of infectious diseases (SINAN); for stillbirths, mortality (SIM). Since there was no unique identifier, we used probabilistic linkage based on maternal name, age and municipality. We compared two probabilistic approaches, each with two thresholds: 1) a bespoke linkage algorithm; 2) a standard linkage software widely used in Brazil (ReclinkIII), and used manual review to identify further links. Sensitivity and positive predictive value (PPV) were estimated using a subset of gold-standard data created through manual review. We examined the characteristics of false-matches and missed-matches to identify any sources of bias. From records of 678,999 dengue cases and 62,373 stillbirths, the gold-standard linkage identified 191 cases. The bespoke linkage algorithm with a conservative threshold produced 131 links, with sensitivity = 64.4% (68 missed-matches) and PPV = 92.5% (8 false-matches). Manual review of uncertain links identified an additional 37 links, increasing sensitivity to 83.7%. The bespoke algorithm with a relaxed threshold identified 132 true matches (sensitivity = 69.1%), but introduced 61 false-matches (PPV = 68.4%). ReclinkIII produced lower sensitivity and PPV than the bespoke linkage algorithm. Linkage error was not associated with any recorded study variables. Despite a lack of unique identifiers for linking mothers and stillbirths, we demonstrate a high standard of linkage of large routine databases from a middle income country. Probabilistic linkage and manual review were essential for accurately identifying cases for a case-control study, but this approach may not be feasible for larger databases or for linkage of more common outcomes.

DNA Commission of the International Society for Forensic Genetics (ISFG): Guidelines on the use of X-STRs in kinship analysis.

PubMed

Tillmar, Andreas O; Kling, Daniel; Butler, John M; Parson, Walther; Prinz, Mechthild; Schneider, Peter M; Egeland, Thore; Gusmão, Leonor

2017-07-01

Forensic genetic laboratories perform an increasing amount of genetic analyses of the X chromosome, in particular to solve complex cases of kinship analysis. For some biological relationships X-chromosomal markers can be more informative than autosomal markers, and there are a large number of markers, methods and databases that have been described for forensic use. Due to their particular mode of inheritance, and their physical location on a single chromosome, some specific considerations are required when estimating the weight of evidence for X-chromosomal marker DNA data. The DNA Commission of the International Society for Forensic Genetics (ISFG) hereby presents guidelines and recommendations for the use of X-chromosomal markers in kinship analysis with a special focus on the biostatistical evaluation. Linkage and linkage disequilibrium (association of alleles) are of special importance for such evaluations and these concepts and the implications for likelihood calculations are described in more detail. Furthermore it is important to use appropriate computer software that accounts for linkage and linkage disequilibrium among loci, as well as for mutations. Even though some software exist, there is still a need for further improvement of dedicated software. Copyright © 2017 Elsevier B.V. All rights reserved.

Linkage results on 11q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maziade, M.; Raymond, V.; Cliche, D.

The 11q21-22 region is of interest for schizophrenia because several candidate genes are located in this section of the genome. The 11q21-22 region, including DRD2, was surveyed by linkage analysis in a sample (N = 242) made of four large multigenerational pedigrees densely affected by schizophrenia (SZ) and eight others by bipolar disorder (BP). These pedigrees were ascertained in a large area of Eastern Quebec and Northern New Brunswick and are still being extended. Family members were administered a {open_quotes}consensus best-estimate diagnosis procedure{close_quotes} (DSM-III-R criteria) blind to probands and relatives` diagnosis and to pedigree assignment (SZ or BP). For linkagemore » analysis, 11 microsatellite polymorphism (CA repeat) markers, located at 11q21-22, and comprising DRD2, were genotyped. Results show no evidence of a major gene for schizophrenia. However, a maximum lod score of 3.41 at the D11S35 locus was observed in an affected-only analysis of one large SZ family, pedigree 255. Whether or not the positive linkage trend in pedigree 255 reflects a true linkage for a small proportion of SZ needs to be confirmed through the extension of this kindred and through replication. 36 refs., 2 tabs.« less

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

PubMed

Bonné-Tamir, B; Korostishevsky, M; Kalinsky, H; Seroussi, E; Beker, R; Weiss, S; Godel, V

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 were studied in 10 related sibships. DNA samples 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.

Genetic heterogeneity of Usher syndrome type II.

PubMed Central

Pieke Dahl, S; Kimberling, W J; Gorin, M B; Weston, M D; Furman, J M; Pikus, A; Möller, C

1993-01-01

Usher syndrome is an autosomal recessive disorder characterised by retinitis pigmentosa and congenital sensorineural hearing loss. A gene for Usher syndrome type II (USH2) has been localised to chromosome 1q32-q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which are believed to flank USH2. Genotypic results and subsequent linkage analysis indicated non-linkage of this family to these markers. The A test analysis for heterogeneity with this family and 32 other Usher type II families was statistically significant at p < 0.05. Further clinical evaluation of this family was done in light of the linkage results to determine if any phenotypic characteristics would allow for clinical identification of the unlinked type. No clear phenotypic differences were observed; however, this unlinked family may represent a previously unreported subtype of Usher type II characterised by a milder form of retinitis pigmentosa and mild vestibular abnormalities. Heterogeneity of Usher syndrome type II complicates efforts to isolate and clone Usher syndrome genes using linkage analysis and limits the use of DNA markers in early detection of Usher type II. Images PMID:7901420

Genetic dissection of seed oil and protein content and identification of networks associated with oil content in Brassica napus.

PubMed

Chao, Hongbo; Wang, Hao; Wang, Xiaodong; Guo, Liangxing; Gu, Jianwei; Zhao, Weiguo; Li, Baojun; Chen, Dengyan; Raboanatahiry, Nadia; Li, Maoteng

2017-04-10

High-density linkage maps can improve the precision of QTL localization. A high-density SNP-based linkage map containing 3207 markers covering 3072.7 cM of the Brassica napus genome was constructed in the KenC-8 × N53-2 (KNDH) population. A total of 67 and 38 QTLs for seed oil and protein content were identified with an average confidence interval of 5.26 and 4.38 cM, which could explain up to 22.24% and 27.48% of the phenotypic variation, respectively. Thirty-eight associated genomic regions from BSA overlapped with and/or narrowed the SOC-QTLs, further confirming the QTL mapping results based on the high-density linkage map. Potential candidates related to acyl-lipid and seed storage underlying SOC and SPC, respectively, were identified and analyzed, among which six were checked and showed expression differences between the two parents during different embryonic developmental periods. A large primary carbohydrate pathway based on potential candidates underlying SOC- and SPC-QTLs, and interaction networks based on potential candidates underlying SOC-QTLs, was constructed to dissect the complex mechanism based on metabolic and gene regulatory features, respectively. Accurate QTL mapping and potential candidates identified based on high-density linkage map and BSA analyses provide new insights into the complex genetic mechanism of oil and protein accumulation in the seeds of rapeseed.

Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets.

PubMed

Saeed, Mohammad

2017-05-01

Systemic lupus erythematosus (SLE) is a complex disorder. Genetic association studies of complex disorders suffer from the following three major issues: phenotypic heterogeneity, false positive (type I error), and false negative (type II error) results. Hence, genes with low to moderate effects are missed in standard analyses, especially after statistical corrections. OASIS is a novel linkage disequilibrium clustering algorithm that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders such as SLE. OASIS was applied to two SLE dbGAP GWAS datasets (6077 subjects; ∼0.75 million single-nucleotide polymorphisms). OASIS identified three known SLE genes viz. IFIH1, TNIP1, and CD44, not previously reported using these GWAS datasets. In addition, 22 novel loci for SLE were identified and the 5 SLE genes previously reported using these datasets were verified. OASIS methodology was validated using single-variant replication and gene-based analysis with GATES. This led to the verification of 60% of OASIS loci. New SLE genes that OASIS identified and were further verified include TNFAIP6, DNAJB3, TTF1, GRIN2B, MON2, LATS2, SNX6, RBFOX1, NCOA3, and CHAF1B. This study presents the OASIS algorithm, software, and the meta-analyses of two publicly available SLE GWAS datasets along with the novel SLE genes. Hence, OASIS is a novel linkage disequilibrium clustering method that can be universally applied to existing GWAS datasets for the identification of new genes.

Parsing the genetic heterogeneity of chromosome 12q susceptibility genes for Alzheimer disease by family-based association analysis.

PubMed

Lin, Ping-I; Martin, Eden R; Browning-Large, Carrie A; Schmechel, Donald E; Welsh-Bohmer, Kathleen A; Doraiswamy, P Murali; Gilbert, John R; Haines, Jonathan L; Pericak-Vance, Margaret A

2006-07-01

Previous linkage studies have suggested that chromosome 12 may harbor susceptibility genes for late-onset Alzheimer disease (LOAD). No risk genes on chromosome 12 have been conclusively identified yet. We have reported that the linkage evidence for LOAD in a 12q region was significantly increased in autopsy-confirmed families particularly for those showing no linkage to alpha-T catenin gene, a LOAD candidate gene on chromosome 10 [LOD score increased from 0.1 in the autopsy-confirmed subset to 4.19 in the unlinked subset (optimal subset); p<0.0001 for the increase in LOD score], indicating a one-LOD support interval spanning 6 Mb. To further investigate this finding and to identify potential candidate LOAD risk genes for follow-up analysis, we analyzed 99 single nucleotide polymorphisms in this region, for the overall sample, the autopsy-confirmed subset, and the optimal subset, respectively, for comparison. We saw no significant association (p<0.01) in the overall sample. In the autopsy-confirmed subset, the best finding was obtained in the activation transcription factor 7 (ATF7) gene (single-locus association, p=0.002; haplotype association global, p=0.007). In the optimal subset, the best finding was obtained in the hypothetical protein FLJ20436 (FLJ20436) gene (single-locus association, p=0.0026). These results suggest that subset and covariate analyses may be one approach to help identify novel susceptibility genes on chromosome 12q for LOAD.

Linkage and association study of late-onset Alzheimer disease families linked to 9p21.3.

PubMed

Züchner, S; Gilbert, J R; Martin, E R; Leon-Guerrero, C R; Xu, P-T; Browning, C; Bronson, P G; Whitehead, P; Schmechel, D E; Haines, J L; Pericak-Vance, M A

2008-11-01

A chromosomal locus for late-onset Alzheimer disease (LOAD) has previously been mapped to 9p21.3. The most significant results were reported in a sample of autopsy-confirmed families. Linkage to this locus has been independently confirmed in AD families from a consanguineous Israeli-Arab community. In the present study we analyzed an expanded clinical sample of 674 late-onset AD families, independently ascertained by three different consortia. Sample subsets were stratified by site and autopsy-confirmation. Linkage analysis of a dense array of SNPs across the chromosomal locus revealed the most significant results in the 166 autopsy-confirmed families of the NIMH sample. Peak HLOD scores of 4.95 at D9S741 and 2.81 at the nearby SNP rs2772677 were obtained in a dominant model. The linked region included the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), which has been suggested as an AD candidate gene. By re-sequencing all exons in the vicinity of CDKN2A in 48 AD cases, we identified and genotyped four novel SNPs, including a non-synonymous, a synonymous, and two variations located in untranslated RNA sequences. Family-based allelic and genotypic association analysis yielded significant results in CDKN2A (rs11515: PDT p = 0.003, genotype-PDT p = 0.014). We conclude that CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p.

Clinical reinvestigation and linkage analysis in the family with Episkopi blindness (Norrie disease).

PubMed

Wolff, G; Mayerová, A; Wienker, T F; Atalianis, P; Ioannou, P; Warburg, M

1992-11-01

We present the results of a clinical and genetic reinvestigation of the Cypriot family affected by an X chromosomally inherited eye disease originally published by Taylor et al, who coined the term Episkopi blindness. The pedigree was extended to 160 members, including 16 affected males out of 48 males at risk for the disease, most of whom were seen by one of us (PA). Affected males are blind with no associated symptoms and apparently are not mentally retarded. Thirty-nine family members agreed to blood sampling for genetic investigations. RFLP analysis was performed using probes from the region known to be deleted in some Norrie patients and polymorphic markers (DXS77, DXS7, MAOA, DXS255) from the proximal short arm of the X chromosome. There was no deletion for any of the probes in the affected males. Linkage analysis yielded positive lod scores for all informative markers (Z (DXS255, theta = 0) = 6.54, Z (MAOA, theta = 0) = 2.23, Z (DXS7, theta = 0) = 2.13). Thus, the conclusion that Episkopi blindness and Norrie disease (NDP, MIM *310600) are the same entity based on clinical evidence is now reinforced by gene mapping.

A statistical design for testing apomictic diversification through linkage analysis.

PubMed

Zeng, Yanru; Hou, Wei; Song, Shuang; Feng, Sisi; Shen, Lin; Xia, Guohua; Wu, Rongling

2014-03-01

The capacity of apomixis to generate maternal clones through seed reproduction has made it a useful characteristic for the fixation of heterosis in plant breeding. It has been observed that apomixis displays pronounced intra- and interspecific diversification, but the genetic mechanisms underlying this diversification remains elusive, obstructing the exploitation of this phenomenon in practical breeding programs. By capitalizing on molecular information in mapping populations, we describe and assess a statistical design that deploys linkage analysis to estimate and test the pattern and extent of apomictic differences at various levels from genotypes to species. The design is based on two reciprocal crosses between two individuals each chosen from a hermaphrodite or monoecious species. A multinomial distribution likelihood is constructed by combining marker information from two crosses. The EM algorithm is implemented to estimate the rate of apomixis and test its difference between two plant populations or species as the parents. The design is validated by computer simulation. A real data analysis of two reciprocal crosses between hickory (Carya cathayensis) and pecan (C. illinoensis) demonstrates the utilization and usefulness of the design in practice. The design provides a tool to address fundamental and applied questions related to the evolution and breeding of apomixis.

Clinical reinvestigation and linkage analysis in the family with Episkopi blindness (Norrie disease).

PubMed Central

Wolff, G; Mayerová, A; Wienker, T F; Atalianis, P; Ioannou, P; Warburg, M

1992-01-01

We present the results of a clinical and genetic reinvestigation of the Cypriot family affected by an X chromosomally inherited eye disease originally published by Taylor et al, who coined the term Episkopi blindness. The pedigree was extended to 160 members, including 16 affected males out of 48 males at risk for the disease, most of whom were seen by one of us (PA). Affected males are blind with no associated symptoms and apparently are not mentally retarded. Thirty-nine family members agreed to blood sampling for genetic investigations. RFLP analysis was performed using probes from the region known to be deleted in some Norrie patients and polymorphic markers (DXS77, DXS7, MAOA, DXS255) from the proximal short arm of the X chromosome. There was no deletion for any of the probes in the affected males. Linkage analysis yielded positive lod scores for all informative markers (Z (DXS255, theta = 0) = 6.54, Z (MAOA, theta = 0) = 2.23, Z (DXS7, theta = 0) = 2.13). Thus, the conclusion that Episkopi blindness and Norrie disease (NDP, MIM *310600) are the same entity based on clinical evidence is now reinforced by gene mapping. Images PMID:1453434

Linkage analysis of chromosome 22q12-13 in a United Kingdom/Icelandic sample of 23 multiplex schizophrenia families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalsi, G.; Read, T.; Butler, R.

A possible linkage to a genetic subtype of schizophrenia and related disorders has been reported on the long arm of chromosome 22 at q12-13. However formal statistical tests in a combined sample could not reject homogeneity and prove that there was linked subgroup of families. We have studied 23 schizophrenia pedigrees to test whether some multiplex schizophrenia families may be linked to the microsatellite markers D22S274 and D22S283 which span the 22q12-13 region. Two point followed by multipoint lod and non-parametric linkage analyses under the assumption of heterogeneity provided no evidence for linkage over the relevant region. 16 refs., 4more » tabs.« less

Modifier gene study of meconium ileus in cystic fibrosis: statistical considerations and gene mapping results

PubMed Central

Dorfman, Ruslan; Li, Weili; Sun, Lei; Lin, Fan; Wang, Yongqian; Sandford, Andrew; Paré, Peter D.; McKay, Karen; Kayserova, Hana; Piskackova, Tereza; Macek, Milan; Czerska, Kamila; Sands, Dorota; Tiddens, Harm; Margarit, Sonia; Repetto, Gabriela; Sontag, Marci K.; Accurso, Frank J.; Blackman, Scott; Cutting, Garry R.; Tsui, Lap-Chee; Corey, Mary; Durie, Peter; Zielenski, Julian; Strug, Lisa J.

2010-01-01

Cystic fibrosis (CF) is a monogenic disease due to mutations in the CFTR gene. Yet, variability in CF disease presentation is presumed to be affected by modifier genes, such as those recently demonstrated for the pulmonary aspect. Here, we conduct a modifier gene study for meconium ileus (MI), an intestinal obstruction that occurs in 16–20% of CF newborns, providing linkage and association results from large family and case–control samples. Linkage analysis of modifier traits is different than linkage analysis of primary traits on which a sample was ascertained. Here, we articulate a source of confounding unique to modifier gene studies and provide an example of how one might overcome the confounding in the context of linkage studies. Our linkage analysis provided evidence of a MI locus on chromosome 12p13.3, which was segregating in up to 80% of MI families with at least one affected offspring (HLOD = 2.9). Fine mapping of the 12p13.3 region in a large case–control sample of pancreatic insufficient Canadian CF patients with and without MI pointed to the involvement of ADIPOR2 in MI (p = 0.002). This marker was substantially out of Hardy–Weinberg equilibrium in the cases only, and provided evidence of a cohort effect. The association with rs9300298 in the ADIPOR2 gene at the 12p13.3 locus was replicated in an independent sample of CF families. A protective locus, using the phenotype of no-MI, mapped to 4q13.3 (HLOD = 3.19), with substantial heterogeneity. A candidate gene in the region, SLC4A4, provided preliminary evidence of association (p = 0.002), warranting further follow-up studies. Our linkage approach was used to direct our fine-mapping studies, which uncovered two potential modifier genes worthy of follow-up. PMID:19662435

Quantifying sources of bias in longitudinal data linkage studies of child abuse and neglect: measuring impact of outcome specification, linkage error, and partial cohort follow-up.

PubMed

Parrish, Jared W; Shanahan, Meghan E; Schnitzer, Patricia G; Lanier, Paul; Daniels, Julie L; Marshall, Stephen W

2017-12-01

Health informatics projects combining statewide birth populations with child welfare records have emerged as a valuable approach to conducting longitudinal research of child maltreatment. The potential bias resulting from linkage misspecification, partial cohort follow-up, and outcome misclassification in these studies has been largely unexplored. This study integrated epidemiological survey and novel administrative data sources to establish the Alaska Longitudinal Child Abuse and Neglect Linkage (ALCANLink) project. Using these data we evaluated and quantified the impact of non-linkage misspecification and single source maltreatment ascertainment use on reported maltreatment risk and effect estimates. The ALCANLink project integrates the 2009-2011 Alaska Pregnancy Risk Assessment Monitoring System (PRAMS) sample with multiple administrative databases through 2014, including one novel administrative source to track out-of-state emigration. For this project we limited our analysis to the 2009 PRAMS sample. We report on the impact of linkage quality, cohort follow-up, and multisource outcome ascertainment on the incidence proportion of reported maltreatment before age 6 and hazard ratios of selected characteristics that are often available in birth cohort linkage studies of maltreatment. Failure to account for out-of-state emigration biased the incidence proportion by 12% (from 28.3% w to 25.2% w ), and the hazard ratio (HR) by as much as 33% for some risk factors. Overly restrictive linkage parameters biased the incidence proportion downwards by 43% and the HR by as much as 27% for some factors. Multi-source linkages, on the other hand, were of little benefit for improving reported maltreatment ascertainment. Using the ALCANLink data which included a novel administrative data source, we were able to observe and quantify bias to both the incidence proportion and HR in a birth cohort linkage study of reported child maltreatment. Failure to account for out-of-state emigration and low-quality linkage methods may induce bias in longitudinal data linkage studies of child maltreatment which other researchers should be aware of. In this study multi-agency linkage did not lead to substantial increased detection of reported maltreatment. The ALCANLink methodology may be a practical approach for other states interested in developing longitudinal birth cohort linkage studies of maltreatment that requires limited resources to implement, provides comprehensive data elements, and can facilitate comparability between studies.

Genetic linkage analysis in 26 families with Bardet-Biedl syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, A.F.; Bruford, E.A.; Mansfield, D.C.

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by polydactyly, obesity, hypogonadism, retinitis pigmentosa, renal anomalies and mental retardation. Clinical heterogeneity is quite marked both within and between families. Linkage has been reported between Bardet-Biedl syndrome and the D16408 marker in chromosomal region 16q21 in an extended Bedouin kindred and, more recently, in a subset of 17 out of 31 families using the PYGM/D11S913 markers in chromosomal region 11q13. We have analyzed linkage to the 16q21 and 11q13 regions and used markers covering chromosomes 2, 3, 17 and 18 in a set of 26 Bardet-Biedl families, each containing at leastmore » two affected individuals, with a total of 57 affected members. Evidence of linkage to the D11S527 locus has been identified assuming linkage homogeneity with a lod score of 2.72 at a recombination fraction of 0.11 (95% limits 0.03-0.25).« less

Fragman: an R package for fragment analysis.

PubMed

Covarrubias-Pazaran, Giovanny; Diaz-Garcia, Luis; Schlautman, Brandon; Salazar, Walter; Zalapa, Juan

2016-04-21

Determination of microsatellite lengths or other DNA fragment types is an important initial component of many genetic studies such as mutation detection, linkage and quantitative trait loci (QTL) mapping, genetic diversity, pedigree analysis, and detection of heterozygosity. A handful of commercial and freely available software programs exist for fragment analysis; however, most of them are platform dependent and lack high-throughput applicability. We present the R package Fragman to serve as a freely available and platform independent resource for automatic scoring of DNA fragment lengths diversity panels and biparental populations. The program analyzes DNA fragment lengths generated in Applied Biosystems® (ABI) either manually or automatically by providing panels or bins. The package contains additional tools for converting the allele calls to GenAlEx, JoinMap® and OneMap software formats mainly used for genetic diversity and generating linkage maps in plant and animal populations. Easy plotting functions and multiplexing friendly capabilities are some of the strengths of this R package. Fragment analysis using a unique set of cranberry (Vaccinium macrocarpon) genotypes based on microsatellite markers is used to highlight the capabilities of Fragman. Fragman is a valuable new tool for genetic analysis. The package produces equivalent results to other popular software for fragment analysis while possessing unique advantages and the possibility of automation for high-throughput experiments by exploiting the power of R.

Haplotype Analysis of the Melanopsin Gene in Seasonal Affective Disorder and Controls

DTIC Science & Technology

2007-06-19

Cole, P. A. (2002). Serotonin n-acetyltransferase: Mechanism and inhibition. Current Medicinal Chemistry , 9(12), 1187-1199. 152 APPENDIX A STRUCTURED ...such that low light levels fall below this threshold during winter in individuals with SAD. The present study investigated the haplotype structure of...Association Studies 51 Advantages of Population-Based Case-Control Samples 52 Haplotype Structure 53 Linkage Disequilibrium: A Measure of Correlation Between

A regional land use survey based on remote sensing and other data: A report on a LANDSAT and computer mapping project, volume 1. [Arizona, Colorado, Montana, New Mexico, Utah, and Wyoming

NASA Technical Reports Server (NTRS)

Nez, G. (Principal Investigator); Mutter, D.

1977-01-01

The author has identified the following significant results. New LANDSAT analysis software and linkages with other computer mapping software were developed. Significant results were also achieved in training, communication, and identification of needs for developing the LANDSAT/computer mapping technologies into operational tools for use by decision makers.

Using Cluster Analysis to Compartmentalize a Large Managed Wetland Based on Physical, Biological, and Climatic Geospatial Attributes.

PubMed

Hahus, Ian; Migliaccio, Kati; Douglas-Mankin, Kyle; Klarenberg, Geraldine; Muñoz-Carpena, Rafael

2018-04-27

Hierarchical and partitional cluster analyses were used to compartmentalize Water Conservation Area 1, a managed wetland within the Arthur R. Marshall Loxahatchee National Wildlife Refuge in southeast Florida, USA, based on physical, biological, and climatic geospatial attributes. Single, complete, average, and Ward's linkages were tested during the hierarchical cluster analyses, with average linkage providing the best results. In general, the partitional method, partitioning around medoids, found clusters that were more evenly sized and more spatially aggregated than those resulting from the hierarchical analyses. However, hierarchical analysis appeared to be better suited to identify outlier regions that were significantly different from other areas. The clusters identified by geospatial attributes were similar to clusters developed for the interior marsh in a separate study using water quality attributes, suggesting that similar factors have influenced variations in both the set of physical, biological, and climatic attributes selected in this study and water quality parameters. However, geospatial data allowed further subdivision of several interior marsh clusters identified from the water quality data, potentially indicating zones with important differences in function. Identification of these zones can be useful to managers and modelers by informing the distribution of monitoring equipment and personnel as well as delineating regions that may respond similarly to future changes in management or climate.

Genetic analysis of familial non-syndromic primary failure of eruption

PubMed Central

Frazier-Bowers, S.; Simmons, D; Koehler, K; Zhou, J

2009-01-01

Objectives While some eruption disorders occur as part of a medical syndrome, primary failure of eruption (PFE) – defined as a localized failure of secondary tooth eruption -exists without systemic involvement. Recent studies support that heredity may play an important role in the pathogenesis of PFE. The objective of our human genetic study is to investigate the genetic contribution to PFE. Materials and Methods Four candidate genes POSTN, RUNX2, AMELX, and AMBN) were investigated due to their relationship to tooth eruption or putative relationship to each other. Families and individuals were ascertained based on the clinical diagnosis of PFE. Pedigrees were constructed and analyzed by inspection to determine the mode of inheritance in 4 families. The candidate genes were directly sequenced for both unrelated affected individuals and unaffected individuals. A genome wide scan using 500 microsatellite markers followed by linkage analysis was carried out for one family. Results Pedigree analysis of families suggests an autosomal dominant inheritance pattern with complete penetrance and variable expressivity. Sequence analysis revealed 2 non-functional polymorphisms in the POSTN gene and no other sequence variations in the remaining candidate genes. Genotyping and linkage analysis of one family yielded a LOD score of 1.51 for markers D13S272; D15S118 and D17S831 on chromosomes 13, 15 and 17 respectively. Conclusions While LOD scores were not significant evidence of linkage, extension of current pedigrees and novel SNP chip technology holds great promise for identification of a causative locus for PFE. Clinical Relevance When the process of normal tooth eruption fails, it may result in a clinically guarded or hopeless prognosis. Our studies aim to understand the etiological basis of Primary Failure of Eruption (PFE) toward the development of future orthodontic or pharmocologic interventions that will successfully treat this problem. PMID:19419450

A comprehensive screen for SNP associations on chromosome region 5q31-33 in Swedish/Norwegian celiac disease families.

PubMed

Amundsen, Silja Svanstrøm; Adamovic, Svetlana; Hellqvist, Asa; Nilsson, Staffan; Gudjónsdóttir, Audur H; Ascher, Henry; Ek, Johan; Larsson, Kristina; Wahlström, Jan; Lie, Benedicte A; Sollid, Ludvig M; Naluai, Asa Torinsson

2007-09-01

Celiac disease (CD) is a gluten-induced enteropathy, which results from the interplay between environmental and genetic factors. There is a strong human leukocyte antigen (HLA) association with the disease, and HLA-DQ alleles represent a major genetic risk factor. In addition to HLA-DQ, non-HLA genes appear to be crucial for CD development. Chromosomal region 5q31-33 has demonstrated linkage with CD in several genome-wide studies, including in our Swedish/Norwegian cohort. In a European meta-analysis 5q31-33 was the only region that reached a genome-wide level of significance except for the HLA region. To identify the genetic variant(s) responsible for this linkage signal, we performed a comprehensive single nucleotide polymorphism (SNP) association screen in 97 Swedish/Norwegian multiplex families who demonstrate linkage to the region. We selected tag SNPs from a 16 Mb region representing the 95% confidence interval of the linkage peak. A total of 1,404 SNPs were used for the association analysis. We identified several regions with SNPs demonstrating moderate single- or multipoint associations. However, the isolated association signals appeared insufficient to account for the linkage signal seen in our cohort. Collective effects of multiple risk genes within the region, incomplete genetic coverage or effects related to copy number variation are possible explanations for our findings.

Construction of an Integrated High Density Simple Sequence Repeat Linkage Map in Cultivated Strawberry (Fragaria × ananassa) and its Applicability

PubMed Central

Isobe, Sachiko N.; Hirakawa, Hideki; Sato, Shusei; Maeda, Fumi; Ishikawa, Masami; Mori, Toshiki; Yamamoto, Yuko; Shirasawa, Kenta; Kimura, Mitsuhiro; Fukami, Masanobu; Hashizume, Fujio; Tsuji, Tomoko; Sasamoto, Shigemi; Kato, Midori; Nanri, Keiko; Tsuruoka, Hisano; Minami, Chiharu; Takahashi, Chika; Wada, Tsuyuko; Ono, Akiko; Kawashima, Kumiko; Nakazaki, Naomi; Kishida, Yoshie; Kohara, Mitsuyo; Nakayama, Shinobu; Yamada, Manabu; Fujishiro, Tsunakazu; Watanabe, Akiko; Tabata, Satoshi

2013-01-01

The cultivated strawberry (Fragaria× ananassa) is an octoploid (2n = 8x = 56) of the Rosaceae family whose genomic architecture is still controversial. Several recent studies support the AAA′A′BBB′B′ model, but its complexity has hindered genetic and genomic analysis of this important crop. To overcome this difficulty and to assist genome-wide analysis of F. × ananassa, we constructed an integrated linkage map by organizing a total of 4474 of simple sequence repeat (SSR) markers collected from published Fragaria sequences, including 3746 SSR markers [Fragaria vesca expressed sequence tag (EST)-derived SSR markers] derived from F. vesca ESTs, 603 markers (F. × ananassa EST-derived SSR markers) from F. × ananassa ESTs, and 125 markers (F. × ananassa transcriptome-derived SSR markers) from F. × ananassa transcripts. Along with the previously published SSR markers, these markers were mapped onto five parent-specific linkage maps derived from three mapping populations, which were then assembled into an integrated linkage map. The constructed map consists of 1856 loci in 28 linkage groups (LGs) that total 2364.1 cM in length. Macrosynteny at the chromosome level was observed between the LGs of F. × ananassa and the genome of F. vesca. Variety distinction on 129 F. × ananassa lines was demonstrated using 45 selected SSR markers. PMID:23248204

A hierarchical and modular approach to the discovery of robust associations in genome-wide association studies from pooled DNA samples

PubMed Central

Sebastiani, Paola; Zhao, Zhenming; Abad-Grau, Maria M; Riva, Alberto; Hartley, Stephen W; Sedgewick, Amanda E; Doria, Alessandro; Montano, Monty; Melista, Efthymia; Terry, Dellara; Perls, Thomas T; Steinberg, Martin H; Baldwin, Clinton T

2008-01-01

Background One of the challenges of the analysis of pooling-based genome wide association studies is to identify authentic associations among potentially thousands of false positive associations. Results We present a hierarchical and modular approach to the analysis of genome wide genotype data that incorporates quality control, linkage disequilibrium, physical distance and gene ontology to identify authentic associations among those found by statistical association tests. The method is developed for the allelic association analysis of pooled DNA samples, but it can be easily generalized to the analysis of individually genotyped samples. We evaluate the approach using data sets from diverse genome wide association studies including fetal hemoglobin levels in sickle cell anemia and a sample of centenarians and show that the approach is highly reproducible and allows for discovery at different levels of synthesis. Conclusion Results from the integration of Bayesian tests and other machine learning techniques with linkage disequilibrium data suggest that we do not need to use too stringent thresholds to reduce the number of false positive associations. This method yields increased power even with relatively small samples. In fact, our evaluation shows that the method can reach almost 70% sensitivity with samples of only 100 subjects. PMID:18194558

Genetics and epidemiology, congenital anomalies and cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedman, J.M.

1997-03-01

Many of the basic statistical methods used in epidemiology - regression, analysis of variance, and estimation of relative risk, for example - originally were developed for the genetic analysis of biometric data. The familiarity that many geneticists have with this methodology has helped geneticists to understand and accept genetic epidemiology as a scientific discipline. It worth noting, however, that most of the work in genetic epidemiology during the past decade has been devoted to linkage and other family studies, rather than to population-based investigations of the type that characterize much of mainstream epidemiology. 30 refs., 2 tabs.

Relative Linkages of Chlorophyll-a with the Hydroclimatic and Biogeochemical Variables across the Continental U.S. (CONUS)

NASA Astrophysics Data System (ADS)

Ahmed, M. H.; Abdul-Aziz, O. I.

2017-12-01

Chlorophyll-a (Chl-a) is a key indicator for stream water quality and ecological health. The characterization of interplay between Chl-a and its numerous hydroclimatic and biogeochemical drivers is complex, and often involves multicollinear datasets. A systematic data analytics methodology was employed to determine the relative linkages of stream Chl-a with its dynamic environmental drivers at 50 stream water quality monitoring stations across the continental U.S. Multivariate statistical techniques of principal component analysis (PCA) and factor analysis (FA), in concert with Pearson correlation analysis, were applied to evaluate interrelationships among hydroclimatic, biogeochemical, and biological variables. Power-law based partial least square regression (PLSR) models were developed with a bootstrap Monte Carlo procedure (1000 iterations) to reliably estimate the comparative linkages of Chl-a by resolving multicollinearity in the data matrices (Nash-Sutcliff efficiency = 0.50-87). The data analytics suggested four environmental regimes of stream Chl-a, as dominated by nutrient, climate, redox, and hydro-atmospheric contributions, respectively. Total phosphorous (TP) was the most dominant driver of stream Chl-a in the nutrient controlled regime. Water temperature demonstrated the strongest control of Chl-a in the climate-dominated regime. Furthermore, pH and stream flow were found to be the most important drivers of Chl-a in the redox and hydro-atmospheric component dominated regimes, respectively. The research led to a significant reduction of dimensionality in the large data matrices, providing quantitative and qualitative insights on the dynamics of stream Chl-a. The findings would be useful to manage stream water quality and ecosystem health in the continental U.S. and around the world under a changing climate and environment.

Record linkage for pharmacoepidemiological studies in cancer patients.

PubMed

Herk-Sukel, Myrthe P P van; Lemmens, Valery E P P; Poll-Franse, Lonneke V van de; Herings, Ron M C; Coebergh, Jan Willem W

2012-01-01

An increasing need has developed for the post-approval surveillance of (new) anti-cancer drugs by means of pharmacoepidemiology and outcomes research in the area of oncology. To create an overview that makes researchers aware of the available database linkages in Northern America and Europe which facilitate pharmacoepidemiology and outcomes research in cancer patients. In addition to our own database, i.e. the Eindhoven Cancer Registry (ECR) linked to the PHARMO Record Linkage System, we considered database linkages between a population-based cancer registry and an administrative healthcare database that at least contains information on drug use and offers a longitudinal perspective on healthcare utilization. Eligible database linkages were limited to those that had been used in multiple published articles in English language included in Pubmed. The HMO Cancer Research Network (CRN) in the US was excluded from this review, as an overview of the linked databases participating in the CRN is already provided elsewhere. Researchers who had worked with the data resources included in our review were contacted for additional information and verification of the data presented in the overview. The following database linkages were included: the Surveillance, Epidemiology, and End-Results-Medicare; cancer registry data linked to Medicaid; Canadian cancer registries linked to population-based drug databases; the Scottish cancer registry linked to the Tayside drug dispensing data; linked databases in the Nordic Countries of Europe: Norway, Sweden, Finland and Denmark; and the ECR-PHARMO linkage in the Netherlands. Descriptives of the included database linkages comprise population size, generalizability of the population, year of first data availability, contents of the cancer registry, contents of the administrative healthcare database, the possibility to select a cancer-free control cohort, and linkage to other healthcare databases. The linked databases offer a longitudinal perspective, allowing for observations of health care utilization before, during, and after cancer diagnosis. They create new powerful data resources for the monitoring of post-approval drug utilization, as well as a framework to explore the (cost-)effectiveness of new, often expensive, anti-cancer drugs as used in everyday practice. Copyright © 2011 John Wiley & Sons, Ltd.

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

PubMed Central

2011-01-01

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 genome and considerably extends that of the first-generation map. It will be a valuable resource for ongoing tammar wallaby genetic research and assembling the genome sequence. The sex-pooled map is available online at http://compldb.angis.org.au/. PMID:21854616

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

PubMed

Wang, Chenwei; Webley, Lee; Wei, Ke-jun; Wakefield, Matthew J; Patel, Hardip R; Deakin, Janine E; Alsop, Amber; Marshall Graves, Jennifer A; Cooper, Desmond W; Nicholas, Frank W; Zenger, Kyall R

2011-08-19

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. 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. Construction of this second-generation genetic linkage map is a significant step towards complete coverage of the tammar wallaby genome and considerably extends that of the first-generation map. It will be a valuable resource for ongoing tammar wallaby genetic research and assembling the genome sequence. The sex-pooled map is available online at http://compldb.angis.org.au/.

Genetics of recurrent early-onset major depression (GenRED): significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers.

PubMed

Levinson, Douglas F; Evgrafov, Oleg V; Knowles, James A; Potash, James B; Weissman, Myrna M; Scheftner, William A; Depaulo, J Raymond; Crowe, Raymond R; Murphy-Eberenz, Kathleen; Marta, Diana H; McInnis, Melvin G; Adams, Philip; Gladis, Madeline; Miller, Erin B; Thomas, Jo; Holmans, Peter

2007-02-01

The authors studied a dense map of single nucleotide polymorphism (SNP) DNA markers on chromosome 15q25-q26 to maximize the informativeness of genetic linkage analyses in a region where they previously reported suggestive evidence for linkage of recurrent early-onset major depressive disorder. In 631 European-ancestry families with multiple cases of recurrent early-onset major depressive disorder, 88 SNPs were genotyped, and multipoint allele-sharing linkage analyses were carried out. Marker-marker linkage disequilibrium was minimized, and a simulation study with founder haplotypes from these families suggested that linkage scores were not inflated by linkage disequilibrium. The dense SNP map increased the information content of the analysis from around 0.7 to over 0.9. The maximum evidence for linkage was the Z likelihood ratio score statistic of Kong and Cox (Z(LR))=4.69 at 109.8 cM. The exact p value was below the genomewide significance threshold. By contrast, in the genome scan with microsatellite markers at 9 cM spacing, the maximum Z(LR) for European-ancestry families was 3.43 (106.53 cM). It was estimated that the linked locus or loci in this region might account for a 20% or less populationwide increase in risk to siblings of cases. This region has produced modestly positive evidence for linkage to depression and related traits in other studies. These results suggest that DNA sequence variations in one or more genes in the 15q25-q26 region can increase susceptibility to major depression and that efforts are warranted to identify these genes.

The evolution of spillover effects between oil and stock markets across multi-scales using a wavelet-based GARCH-BEKK model

NASA Astrophysics Data System (ADS)

Liu, Xueyong; An, Haizhong; Huang, Shupei; Wen, Shaobo

2017-01-01

Aiming to investigate the evolution of mean and volatility spillovers between oil and stock markets in the time and frequency dimensions, we employed WTI crude oil prices, the S&P 500 (USA) index and the MICEX index (Russia) for the period Jan. 2003-Dec. 2014 as sample data. We first applied a wavelet-based GARCH-BEKK method to examine the spillover features in frequency dimension. To consider the evolution of spillover effects in time dimension at multiple-scales, we then divided the full sample period into three sub-periods, pre-crisis period, crisis period, and post-crisis period. The results indicate that spillover effects vary across wavelet scales in terms of strength and direction. By analysis the time-varying linkage, we found the different evolution features of spillover effects between the Oil-US stock market and Oil-Russia stock market. The spillover relationship between oil and US stock market is shifting to short-term while the spillover relationship between oil and Russia stock market is changing to all time scales. That result implies that the linkage between oil and US stock market is weakening in the long-term, and the linkage between oil and Russia stock market is getting close in all time scales. This may explain the phenomenon that the US stock index and the Russia stock index showed the opposite trend with the falling of oil price in the post-crisis period.

Genetic mapping and identification of QTL for earliness in the globe artichoke/cultivated cardoon complex.

PubMed

Portis, Ezio; Scaglione, Davide; Acquadro, Alberto; Mauromicale, Giovanni; Mauro, Rosario; Knapp, Steven J; Lanteri, Sergio

2012-05-23

The Asteraceae species Cynara cardunculus (2n = 2x = 34) includes the two fully cross-compatible domesticated taxa globe artichoke (var. scolymus L.) and cultivated cardoon (var. altilis DC). As both are out-pollinators and suffer from marked inbreeding depression, linkage analysis has focussed on the use of a two way pseudo-test cross approach. A set of 172 microsatellite (SSR) loci derived from expressed sequence tag DNA sequence were integrated into the reference C. cardunculus genetic maps, based on segregation among the F1 progeny of a cross between a globe artichoke and a cultivated cardoon. The resulting maps each detected 17 major linkage groups, corresponding to the species' haploid chromosome number. A consensus map based on 66 co-dominant shared loci (64 SSRs and two SNPs) assembled 694 loci, with a mean inter-marker spacing of 2.5 cM. When the maps were used to elucidate the pattern of inheritance of head production earliness, a key commercial trait, seven regions were shown to harbour relevant quantitative trait loci (QTL). Together, these QTL accounted for up to 74% of the overall phenotypic variance. The newly developed consensus as well as the parental genetic maps can accelerate the process of tagging and eventually isolating the genes underlying earliness in both the domesticated C. cardunculus forms. The largest single effect mapped to the same linkage group in each parental maps, and explained about one half of the phenotypic variance, thus representing a good candidate for marker assisted selection.

Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamino, K.; Anderson, L.; O'dahl, S.

1992-11-01

A large number of familial Alzheimer disease (FAD) kindreds were examined to determine whether mutations in the amyloid precursor protein (APP) gene could be responsible for the disease. Previous studies have identified three mutations at APP codon 717 which are pathogenic for Alzheimer disease (AD). Samples from affected subjects were examined for mutations in exons 16 and 17 of the APP gene. A combination of direct sequencing and single-strand conformational polymorphism analysis was used. Sporadic AD and normal controls were also examined by the same methods. Five sequence variants were identified. One variant at APP codon 693 resulted in amore » Glu[yields]Gly change. This is the same codon as the hereditary cerebral hemorrhage with amyloidosis-Dutch type Glu[yields]Gln mutation. Another single-base change at APP codon 708 did not alter the amino acid encoded at this site. Two point mutations and a 6-bp deletion were identified in the intronic sequences surrounding exon 17. None of the variants could be unambigously determined to be responsible for FAD. The larger families were also analyzed by testing for linkage of FAD to a highly polymorphic short tandem repeat marker (D21S210) that is tightly linked to APP. Highly negative LOD scores were obtained for the family groups tested, and linkage was formally excluded beyond [theta] = .10 for the Volga German kindreds, [theta] = .20 for early-onset non-Volga Germans, and [theta] = .10 for late-onset families. LOD scores for linkage of FAD to markers centromeric to APP (D21S1/S11, D21S13, and D21S215) were also negative in the three family groups. These studies show that APP mutations account for AD in only a small fraction of FAD kindreds. 49 refs., 6 figs., 4 tabs.« less

Three Degree of Freedom Parallel Mechanical Linkage

NASA Technical Reports Server (NTRS)

Adelstein, Bernard D. (Inventor)

1998-01-01

A three degree of freedom parallel mechanism or linkage that couples three degree of freedom translational displacements at an endpoint, such as a handle, a hand grip, or a robot tool, to link rotations about three axes that are fixed with respect to a common base or ground link. The mechanism includes a three degree of freedom spherical linkage formed of two closed loops, and a planar linkage connected to the endpoint. The closed loops are rotatably interconnected, and made of eight rigid links connected by a plurality of single degree of freedom revolute joints. Three of these revolute joints are base joints and are connected to a common ground. such that the axis lines passing through the revolute joints intersect at a common fixed center point K forming the center of a spherical work volume in which the endpoint is capable of moving. 'Me three degrees of freedom correspond to the spatial displacement of the endpoint, for instance. The mechanism provides a new overall spatial kinematic linkage composed of a minimal number of rigid links and rotary joints. The mechanism has improved mechanical stiffness, and conveys mechanical power bidirectionally between the human operator and the electromechanical actuators. It does not require gears, belts. cable, screw or other types of transmission elements, and is useful in applications requiring full backdrivability. Thus, this invention can serve as the mechanical linkage for actively powered devices such as compliant robotic manipulators and force-reflecting hand controllers, and passive devices such as manual input devices for computers and other systems.

HIV-1 transmission linkage in an HIV-1 prevention clinical trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leitner, Thomas; Campbell, Mary S; Mullins, James I

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 determinationmore » 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 determination process.« less

Viral Linkage in HIV-1 Seroconverters and Their Partners in an HIV-1 Prevention Clinical Trial

PubMed Central

Campbell, Mary S.; Mullins, James I.; Hughes, James P.; Celum, Connie; Wong, Kim G.; Raugi, Dana N.; Sorensen, Stefanie; Stoddard, Julia N.; Zhao, Hong; Deng, Wenjie; Kahle, Erin; Panteleeff, Dana; Baeten, Jared M.; McCutchan, Francine E.; Albert, Jan; Leitner, Thomas; Wald, Anna; Corey, Lawrence; Lingappa, Jairam R.

2011-01-01

Background Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519) was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners. Methodology/Principal Findings We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ≥50%. Adjudicators classified each seroconversion, finding 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%). Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters. Conclusions/Significance 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 determination process. PMID:21399681

Linkage Analysis of Urine Arsenic Species Patterns in the Strong Heart Family Study

PubMed Central

Gribble, Matthew O.; Voruganti, Venkata Saroja; Cole, Shelley A.; Haack, Karin; Balakrishnan, Poojitha; Laston, Sandra L.; Tellez-Plaza, Maria; Francesconi, Kevin A.; Goessler, Walter; Umans, Jason G.; Thomas, Duncan C.; Gilliland, Frank; North, Kari E.; Franceschini, Nora; Navas-Acien, Ana

2015-01-01

Arsenic toxicokinetics are important for disease risks in exposed populations, but genetic determinants are not fully understood. We examined urine arsenic species patterns measured by HPLC-ICPMS among 2189 Strong Heart Study participants 18 years of age and older with data on ∼400 genome-wide microsatellite markers spaced ∼10 cM and arsenic speciation (683 participants from Arizona, 684 from Oklahoma, and 822 from North and South Dakota). We logit-transformed % arsenic species (% inorganic arsenic, %MMA, and %DMA) and also conducted principal component analyses of the logit % arsenic species. We used inverse-normalized residuals from multivariable-adjusted polygenic heritability analysis for multipoint variance components linkage analysis. We also examined the contribution of polymorphisms in the arsenic metabolism gene AS3MT via conditional linkage analysis. We localized a quantitative trait locus (QTL) on chromosome 10 (LOD 4.12 for %MMA, 4.65 for %DMA, and 4.84 for the first principal component of logit % arsenic species). This peak was partially but not fully explained by measured AS3MT variants. We also localized a QTL for the second principal component of logit % arsenic species on chromosome 5 (LOD 4.21) that was not evident from considering % arsenic species individually. Some other loci were suggestive or significant for 1 geographical area but not overall across all areas, indicating possible locus heterogeneity. This genome-wide linkage scan suggests genetic determinants of arsenic toxicokinetics to be identified by future fine-mapping, and illustrates the utility of principal component analysis as a novel approach that considers % arsenic species jointly. PMID:26209557

Self-assembly and electrical characteristics of 4-pentynoic acid functionalized Fe3O4-γ-Fe2O3 nanoparticles on SiO2/n-Si

NASA Astrophysics Data System (ADS)

Baharuddin, Aainaa Aqilah; Ang, Bee Chin; Wong, Yew Hoong

2017-11-01

A novel investigation on a relationship between temperature-influential self-assembly (70-300 °C) of 4-pentynoic acid functionalized Fe3O4-γ-Fe2O3 nanoparticles (NPs) on SiO2/n-Si with electrical properties was reported with the interests for metal-oxide-semiconductor applications. X-ray diffractometer (XRD) analysis conveyed that 8 ± 1 nm of the NPs were assembled. Increasing heating temperature induced growth of native oxide (SiO2). Raman analysis confirmed the coexistence of Fe3O4-γ-Fe2O3. Attenuated Total Reflectance Infrared (ATR-IR) spectra showed that self-assembly occurred via Sisbnd Osbnd C linkages. While Sisbnd Osbnd C linkages were broken down at elevated temperatures, formations of Si-OH defects were amplified; a consequence of physisorbed surfactants disintegration. Atomic force microscopy (AFM) showed that sample with more physisorbed surfactants exhibited the highest root-mean-square (RMS) roughness (18.12 ± 7.13 nm) whereas sample with lesser physisorbed surfactants displayed otherwise (12.99 ± 4.39 nm RMS roughness). Field Emission Scanning Electron Microscope (FE-SEM) analysis showed non-uniform aggregation of the NPs, deposited as film (12.6 μm thickness). The increased saturation magnetization (71.527 A m2/kg) and coercivity (929.942 A/m) acquired by vibrating sample magnetometer (VSM) of the sample heated at 300 °C verified the surfactants' disintegration. Leakage current density-electric field (J-E) characteristics showed that sample heated at 150 °C with the most aggregated NPs as well as the most developed Sisbnd Osbnd C linkages demonstrated the highest breakdown field and barrier height at 2.58 × 10-3 MV/cm and 0.38 eV respectively. Whereas sample heated at 300 °C with the least Sisbnd Osbnd C linkages as well as lesser aggregated NPs showed the lowest breakdown field and barrier height at 1.08 × 10-3 MV/cm and 0.19 eV respectively. This study opens up better understandings on how formation and breaking down of covalent linkages as well as accumulation of defects, particularly prior temperature influential self-assembly at the interfaces, affected electrical breakdown field and barrier height. Hence, possible future development of self-assembly silicon-based metal-oxide-semiconductor (MOS) structure particularly in the presence of SiO2 can be deliberated.

Linkage Analysis in Autoimmune Addison's Disease: NFATC1 as a Potential Novel Susceptibility Locus.

PubMed

Mitchell, Anna L; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U; Vaidya, Bijay; Erichsen, Martina M; Darlay, Rebecca; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S

2015-01-01

Autoimmune Addison's disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.

A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16.

PubMed

Asherson, P; Zhou, K; Anney, R J L; Franke, B; Buitelaar, J; Ebstein, R; Gill, M; Altink, M; Arnold, R; Boer, F; Brookes, K; Buschgens, C; Butler, L; Cambell, D; Chen, W; Christiansen, H; Feldman, L; Fleischman, K; Fliers, E; Howe-Forbes, R; Goldfarb, A; Heise, A; Gabriëls, I; Johansson, L; Lubetzki, I; Marco, R; Medad, S; Minderaa, R; Mulas, F; Müller, U; Mulligan, A; Neale, B; Rijsdijk, F; Rabin, K; Rommelse, N; Sethna, V; Sorohan, J; Uebel, H; Psychogiou, L; Weeks, A; Barrett, R; Xu, X; Banaschewski, T; Sonuga-Barke, E; Eisenberg, J; Manor, I; Miranda, A; Oades, R D; Roeyers, H; Rothenberger, A; Sergeant, J; Steinhausen, H-C; Taylor, E; Thompson, M; Faraone, S V

2008-05-01

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

DNA linkage studies of degenerative retinal diseases.

PubMed

Daiger, S P; Heckenlively, J R; Lewis, R A; Pelias, M Z

1987-01-01

DNA linkage studies of human genetic diseases have led to rapid characterization of a number of otherwise intractable disease loci. Detection of a linked DNA marker, the first step in "reverse genetics", has permitted cloning of the genes for Duchenne muscular dystrophy, retinoblastoma and chronic granulomatosis disease, among others. Thus, the case for applying these techniques to retinitis pigmentosa and related diseases, and the urgency in capitalizing on molecular developments, is justified and compelling. The first major success regarding RP was in demonstrating linkage of the DNA marker DXS7 (L1.28) to XRP. For autosomal forms of the disease, conventional linkage studies have provided tentative evidence for linkage of ADRP to the Rh blood group on chromosome lp and for linkage of Usher's syndrome to Gc and 4q. These provisional assignments are, at least, an important starting point for DNA analysis. The Support Program for DNA Linkage Studies of Degenerative Retinal Diseases was established to provide access for the scientific community to appropriate families, using the resources of the Human Genetic Mutant Cell Repository to prepare, store and distribute lymphoblast lines. To date, two extensive, well-characterized families are included in the program: the autosomal dominant RP family UCLA-RP01, and the Usher's syndrome families LSU-US01. It is highly likely that rapid progress will be made in mapping and characterizing the inherited retinal dystrophies. We believe the support program will facilitate this progress.

Quantitative Trait Loci Controlling Vegetative Growth Rate in the Edible Basidiomycete Pleurotus ostreatus

PubMed Central

Larraya, Luis M.; Idareta, Eneko; Arana, Dani; Ritter, Enrique; Pisabarro, Antonio G.; Ramírez, Lucia

2002-01-01

Mycelium growth rate is a quantitative characteristic that exhibits continuous variation. This trait has applied interest, as growth rate is correlated with production yield and increased advantage against competitors. In this work, we studied growth rate variation in the edible basidiomycete Pleurotus ostreatus growing as monokaryotic or dikaryotic mycelium on Eger medium or on wheat straw. Our analysis resulted in identification of several genomic regions (quantitative trait loci [QTLs]) involved in the control of growth rate that can be mapped on the genetic linkage map of this fungus. In some cases monokaryotic and dikaryotic QTLs clustered at the same map position, indicating that there are principal genomic areas responsible for growth rate control. The availability of this linkage map of growth rate QTLs can help in the design of rational strain breeding programs based on genomic information. PMID:11872457

Computing the shape of brain networks using graph filtration and Gromov-Hausdorff metric.

PubMed

Lee, Hyekyoung; Chung, Moo K; Kang, Hyejin; Kim, Boong-Nyun; Lee, Dong Soo

2011-01-01

The difference between networks has been often assessed by the difference of global topological measures such as the clustering coefficient, degree distribution and modularity. In this paper, we introduce a new framework for measuring the network difference using the Gromov-Hausdorff (GH) distance, which is often used in shape analysis. In order to apply the GH distance, we define the shape of the brain network by piecing together the patches of locally connected nearest neighbors using the graph filtration. The shape of the network is then transformed to an algebraic form called the single linkage matrix. The single linkage matrix is subsequently used in measuring network differences using the GH distance. As an illustration, we apply the proposed framework to compare the FDG-PET based functional brain networks out of 24 attention deficit hyperactivity disorder (ADHD) children, 26 autism spectrum disorder (ASD) children and 11 pediatric control subjects.

The efficiency of average linkage hierarchical clustering algorithm associated multi-scale bootstrap resampling in identifying homogeneous precipitation catchments

NASA Astrophysics Data System (ADS)

Chuan, Zun Liang; Ismail, Noriszura; Shinyie, Wendy Ling; Lit Ken, Tan; Fam, Soo-Fen; Senawi, Azlyna; Yusoff, Wan Nur Syahidah Wan

2018-04-01

Due to the limited of historical precipitation records, agglomerative hierarchical clustering algorithms widely used to extrapolate information from gauged to ungauged precipitation catchments in yielding a more reliable projection of extreme hydro-meteorological events such as extreme precipitation events. However, identifying the optimum number of homogeneous precipitation catchments accurately based on the dendrogram resulted using agglomerative hierarchical algorithms are very subjective. The main objective of this study is to propose an efficient regionalized algorithm to identify the homogeneous precipitation catchments for non-stationary precipitation time series. The homogeneous precipitation catchments are identified using average linkage hierarchical clustering algorithm associated multi-scale bootstrap resampling, while uncentered correlation coefficient as the similarity measure. The regionalized homogeneous precipitation is consolidated using K-sample Anderson Darling non-parametric test. The analysis result shows the proposed regionalized algorithm performed more better compared to the proposed agglomerative hierarchical clustering algorithm in previous studies.

Nucleotide Sequence Diversity and Linkage Disequilibrium of Four Nuclear Loci in Foxtail Millet (Setaria italica).

PubMed

He, Shui-Lian; Yang, Yang; Morrell, Peter L; Yi, Ting-Shuang

2015-01-01

Foxtail millet (Setaria italica (L.) Beauv) is one of the earliest domesticated grains, which has been cultivated in northern China by 8,700 years before present (YBP) and across Eurasia by 4,000 YBP. Owing to a small genome and diploid nature, foxtail millet is a tractable model crop for studying functional genomics of millets and bioenergy grasses. In this study, we examined nucleotide sequence diversity, geographic structure, and levels of linkage disequilibrium at four nuclear loci (ADH1, G3PDH, IGS1 and TPI1) in representative samples of 311 landrace accessions across its cultivated range. Higher levels of nucleotide sequence and haplotype diversity were observed in samples from China relative to other sampled regions. Genetic assignment analysis classified the accessions into seven clusters based on nucleotide sequence polymorphisms. Intralocus LD decayed rapidly to half the initial value within ~1.2 kb or less.

A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.

PubMed

Kamada, Fumiaki; Kure, Shigeo; Kudo, Takayuki; Suzuki, Yoichi; Oshima, Takeshi; Ichinohe, Akiko; Kojima, Kanako; Niihori, Tetsuya; Kanno, Junko; Narumi, Yoko; Narisawa, Ayumi; Kato, Kumi; Aoki, Yoko; Ikeda, Katsuhisa; Kobayashi, Toshimitsu; Matsubara, Yoichi

2006-01-01

Autosomal-dominant, nonsyndromic hearing impairment is clinically and genetically heterogeneous. We encountered a large Japanese pedigree in which nonsyndromic hearing loss was inherited in an autosomal-dominant fashion. A genome-wide linkage study indicated linkage to the DFNA2 locus on chromosome 1p34. Mutational analysis of KCNQ4 encoding a potassium channel revealed a novel one-base deletion in exon 1, c.211delC, which generated a profoundly truncated protein without transmembrane domains (p.Q71fsX138). Previously, six missense mutations and one 13-base deletion, c.211_223del, had been reported in KCNQ4. Patients with the KCNQ4 missense mutations had younger-onset and more profound hearing loss than patients with the 211_223del mutation. In our current study, 12 individuals with the c.211delC mutation manifested late-onset and pure high-frequency hearing loss. Our results support the genotype-phenotype correlation that the KCNQ4 deletions are associated with later-onset and milder hearing impairment than the missense mutations. The phenotypic difference may be caused by the difference in pathogenic mechanisms: haploinsufficiency in deletions and dominant-negative effect in missense mutations.

Assignment of Alzheimer's presenilin-2 (PS-2) gene to 1q42.1 by fluorescence in situ hybridization.

PubMed

Takano, T; Sahara, N; Yamanouchi, Y; Mori, H

1997-01-17

Presenilin-2 (PS-2) was suggested to be localized on 1q31-42 based on linkage analysis and cDNA cloning. The final identification of PS-2 as the causal gene for early-onset familial Alzheimer's disease in Voga-German pedigrees was concluded based on the point mutation found in the candidate cDNA isolated from this familial AD. We present evidence of its physical genome mapping of PS-2 on chromosome 1q42.1 by fluorescence in situ hybridization method.

Linkage and candidate gene analysis of X-linked familial exudative vitreoretinopathy.

PubMed

Shastry, B S; Hejtmancik, J F; Plager, D A; Hartzer, M K; Trese, M T

1995-05-20

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder characterized by avascularity of the peripheral retina, retinal exudates, tractional detachment, and retinal folds. The disorder is most commonly transmitted as an autosomal dominant trait, but X-linked transmission also occurs. To initiate the process of identifying the gene responsible for the X-linked disorder, linkage analysis has been performed with three previously unreported three- or four-generation families. Two-point analysis showed linkage to MAOA (Zmax = 2.1, theta max = 0) and DXS228 (Zmax = 0.5, theta max = 0.11), and this was further confirmed by multipoint analysis with these same markers (Zmax = 2.81 at MAOA), which both lie near the gene causing Norrie disease. Molecular genetic analysis further reveals a missense mutation (R121W) in the third exon of the Norrie's disease gene that perfectly cosegregates with the disease through three generations in one family. This mutation was not detected in the unaffected family members and six normal unrelated controls, suggesting that it is likely to be the pathogenic mutation. Additionally, a polymorphic missense mutation (H127R) was detected in a severely affected patient.

Accuracy of Definitions for Linkage to Care in Persons Living with HIV

PubMed Central

KELLER, Sara C.; YEHIA, Baligh R.; EBERHART, Michael G.; BRADY, Kathleen A.

2013-01-01

Objective To compare the accuracy of linkage to care metrics for patients diagnosed with HIV using retention in care and virologic suppression as the gold standards of effective linkage. Design A retrospective cohort study of patients aged 18 and over with newly-diagnosed HIV infection in the City of Philadelphia, 2007 to 2008. Methods Times from diagnosis to clinic visits or laboratory testing were used as linkage measures. Outcome variables included being retained in care and achieving virologic suppression, 366-730 days after diagnosis. Positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for each linkage measure and retention and virologic suppression outcomes are described. Results Of the 1781 patients in the study, 503 (28.2%) were retained in care in the Ryan White system and 418 (23.5%) achieved virologic suppression 366-730 days after diagnosis. The linkage measure with the highest PPV for retention was having two clinic visits within 365 days of diagnosis, separated by 90 days (74.2%). Having a clinic visit between 21 and 365 days after diagnosis had both the highest NPV for retention (94.5%) and the highest adjusted AUC for retention (0.872). Having two tests within 365 days of diagnosis, separated by 90 days, had the highest adjusted AUC for virologic suppression (0.780). Conclusions Linkage measures associated with clinic visits had higher PPV and NPV for retention, while linkage measures associated with laboratory testing had higher PPV and NPV for retention. Linkage measures should be chosen based on the outcome of interest. PMID:23614992

The importance of including local correlation times in the calculation of inter-proton distances from NMR measurements: ignoring local correlation times leads to significant errors in the conformational analysis of the Glc alpha1-2Glc alpha linkage by NMR spectroscopy.

PubMed

Mackeen, Mukram; Almond, Andrew; Cumpstey, Ian; Enis, Seth C; Kupce, Eriks; Butters, Terry D; Fairbanks, Antony J; Dwek, Raymond A; Wormald, Mark R

2006-06-07

The experimental determination of oligosaccharide conformations has traditionally used cross-linkage 1H-1H NOE/ROEs. As relatively few NOEs are observed, to provide sufficient conformational constraints this method relies on: accurate quantification of NOE intensities (positive constraints); analysis of absent NOEs (negative constraints); and hence calculation of inter-proton distances using the two-spin approximation. We have compared the results obtained by using 1H 2D NOESY, ROESY and T-ROESY experiments at 500 and 700 MHz to determine the conformation of the terminal Glc alpha1-2Glc alpha linkage in a dodecasaccharide and a related tetrasaccharide. For the tetrasaccharide, the NOESY and ROESY spectra produced the same qualitative pattern of linkage cross-peaks but the quantitative pattern, the relative peak intensities, was different. For the dodecasaccharide, the NOESY and ROESY spectra at 500 MHz produced a different qualitative pattern of linkage cross-peaks, with fewer peaks in the NOESY spectrum. At 700 MHz, the NOESY and ROESY spectra of the dodecasaccharide produced the same qualitative pattern of peaks, but again the relative peak intensities were different. These differences are due to very significant differences in the local correlation times for different proton pairs across this glycosidic linkage. The local correlation time for each proton pair was measured using the ratio of the NOESY and T-ROESY cross-relaxation rates, leaving the NOESY and ROESY as independent data sets for calculating the inter-proton distances. The inter-proton distances calculated including the effects of differences in local correlation times give much more consistent results.

Linkage mapping in the oilseed crop Jatropha curcas L. reveals a locus controlling the biosynthesis of phorbol esters which cause seed toxicity

PubMed Central

King, Andrew J; Montes, Luis R; Clarke, Jasper G; Affleck, Julie; Li, Yi; Witsenboer, Hanneke; van der Vossen, Edwin; van der Linde, Piet; Tripathi, Yogendra; Tavares, Evanilda; Shukla, Parul; Rajasekaran, Thirunavukkarasu; van Loo, Eibertus N; Graham, Ian A

2013-01-01

Current efforts to grow the tropical oilseed crop Jatropha curcas L. economically are hampered by the lack of cultivars and the presence of toxic phorbol esters (PE) within the seeds of most provenances. These PE restrict the conversion of seed cake into animal feed, although naturally occurring ‘nontoxic’ provenances exist which produce seed lacking PE. As an important step towards the development of genetically improved varieties of J. curcas, we constructed a linkage map from four F2 mapping populations. The consensus linkage map contains 502 codominant markers, distributed over 11 linkage groups, with a mean marker density of 1.8 cM per unique locus. Analysis of the inheritance of PE biosynthesis indicated that this is a maternally controlled dominant monogenic trait. This maternal control is due to biosynthesis of the PE occurring only within maternal tissues. The trait segregated 3 : 1 within seeds collected from F2 plants, and QTL analysis revealed that a locus on linkage group 8 was responsible for phorbol ester biosynthesis. By taking advantage of the draft genome assemblies of J. curcas and Ricinus communis (castor), a comparative mapping approach was used to develop additional markers to fine map this mutation within 2.3 cM. The linkage map provides a framework for the dissection of agronomic traits in J. curcas, and the development of improved varieties by marker-assisted breeding. The identification of the locus responsible for PE biosynthesis means that it is now possible to rapidly breed new nontoxic varieties. PMID:23898859

Linkage mapping in the oilseed crop Jatropha curcas L. reveals a locus controlling the biosynthesis of phorbol esters which cause seed toxicity.

PubMed

King, Andrew J; Montes, Luis R; Clarke, Jasper G; Affleck, Julie; Li, Yi; Witsenboer, Hanneke; van der Vossen, Edwin; van der Linde, Piet; Tripathi, Yogendra; Tavares, Evanilda; Shukla, Parul; Rajasekaran, Thirunavukkarasu; van Loo, Eibertus N; Graham, Ian A

2013-10-01

Current efforts to grow the tropical oilseed crop Jatropha curcas L. economically are hampered by the lack of cultivars and the presence of toxic phorbol esters (PE) within the seeds of most provenances. These PE restrict the conversion of seed cake into animal feed, although naturally occurring 'nontoxic' provenances exist which produce seed lacking PE. As an important step towards the development of genetically improved varieties of J. curcas, we constructed a linkage map from four F₂ mapping populations. The consensus linkage map contains 502 codominant markers, distributed over 11 linkage groups, with a mean marker density of 1.8 cM per unique locus. Analysis of the inheritance of PE biosynthesis indicated that this is a maternally controlled dominant monogenic trait. This maternal control is due to biosynthesis of the PE occurring only within maternal tissues. The trait segregated 3 : 1 within seeds collected from F₂ plants, and QTL analysis revealed that a locus on linkage group 8 was responsible for phorbol ester biosynthesis. By taking advantage of the draft genome assemblies of J. curcas and Ricinus communis (castor), a comparative mapping approach was used to develop additional markers to fine map this mutation within 2.3 cM. The linkage map provides a framework for the dissection of agronomic traits in J. curcas, and the development of improved varieties by marker-assisted breeding. The identification of the locus responsible for PE biosynthesis means that it is now possible to rapidly breed new nontoxic varieties. © 2013 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Genome-scan analysis for quantitative trait loci in an F2 tilapia hybrid.

PubMed

Cnaani, A; Zilberman, N; Tinman, S; Hulata, G; Ron, M

2004-09-01

We searched for genetic linkage between DNA markers and quantitative trait loci (QTLs) for innate immunity, response to stress, biochemical parameters of blood, and fish size in an F2 population derived from an interspecific tilapia hybrid (Oreochromis mossambicusx O. aureus). A family of 114 fish was scanned for 40 polymorphic microsatellite DNA markers and two polymorphic genes, covering approximately 80% of the tilapia genome. These fish had previously been phenotyped for seven immune-response traits and six blood parameters. Critical values for significance were P <0.05 with the false discovery rate (FDR) controlled at 40%. The genome-scan analysis resulted in 35 significant marker-trait associations, involving 26 markers in 16 linkage groups. In a second experiment, nine markers were re-sampled in a second family of 79 fish of the same species hybrid. Seven markers (GM180, GM553, MHC-I, UNH848, UNH868, UNH898 and UNH925) in five linkage groups (LG 1, 3, 4, 22 and 23) were associated with stress response traits. An additional six markers (GM47, GM552, UNH208, UNH881, UNH952, UNH998) in five linkage groups (LG 4, 16, 19, 20 and 23) were verified for their associations with immune response traits, by linkage to several different traits. The portion of variance explained by each QTL was 11% on average, with a maximum of 29%. The average additive effect of QTLs was 0.2 standard deviation units of stress response traits and fish size, with a maximum of 0.33. In three linkage groups (LG 1, 3 and 23) markers were associated with stress response, body weight and sex determination, confirming the location of QTLs reported by several other studies.

Genetic Mapping and QTL Analysis of Growth-Related Traits in Pinctada fucata Using Restriction-Site Associated DNA Sequencing

PubMed Central

Li, Yaoguo; He, Maoxian

2014-01-01

The pearl oyster, Pinctada fucata (P. fucata), is one of the marine bivalves that is predominantly cultured for pearl production. To obtain more genetic information for breeding purposes, we constructed a high-density linkage map of P. fucata and identified quantitative trait loci (QTL) for growth-related traits. One F1 family, which included the two parents, 48 largest progeny and 50 smallest progeny, was sampled to construct a linkage map using restriction site-associated DNA sequencing (RAD-Seq). With low coverage data, 1956.53 million clean reads and 86,342 candidate RAD loci were generated. A total of 1373 segregating SNPs were used to construct a sex-average linkage map. This spanned 1091.81 centimorgans (cM), with 14 linkage groups and an average marker interval of 1.41 cM. The genetic linkage map coverage, Coa, was 97.24%. Thirty-nine QTL-peak loci, for seven growth-related traits, were identified using the single-marker analysis, nonparametric mapping Kruskal-Wallis (KW) test. Parameters included three for shell height, six for shell length, five for shell width, four for hinge length, 11 for total weight, eight for soft tissue weight and two for shell weight. The QTL peak loci for shell height, shell length and shell weight were all located in linkage group 6. The genotype frequencies of most QTL peak loci showed significant differences between the large subpopulation and the small subpopulation (P<0.05). These results highlight the effectiveness of RAD-Seq as a tool for generation of QTL-targeted and genome-wide marker data in the non-model animal, P. fucata, and its possible utility in marker-assisted selection (MAS). PMID:25369421

Association Analysis in Rice: From Application to Utilization

PubMed Central

Zhang, Peng; Zhong, Kaizhen; Shahid, Muhammad Qasim; Tong, Hanhua

2016-01-01

Association analysis based on linkage disequilibrium (LD) is an efficient way to dissect complex traits and to identify gene functions in rice. Although association analysis is an effective way to construct fine maps for quantitative traits, there are a few issues which need to be addressed. In this review, we will first summarize type, structure, and LD level of populations used for association analysis of rice, and then discuss the genotyping methods and statistical approaches used for association analysis in rice. Moreover, we will review current shortcomings and benefits of association analysis as well as specific types of future research to overcome these shortcomings. Furthermore, we will analyze the reasons for the underutilization of the results within association analysis in rice breeding. PMID:27582745

Heritability and linkage analysis of personality in bipolar disorder.

PubMed

Greenwood, Tiffany A; Badner, Judith A; Byerley, William; Keck, Paul E; McElroy, Susan L; Remick, Ronald A; Dessa Sadovnick, A; Kelsoe, John R

2013-11-01

The many attempts that have been made to identify genes for bipolar disorder (BD) have met with limited success, which may reflect an inadequacy of diagnosis as an informative and biologically relevant phenotype for genetic studies. Here we have explored aspects of personality as quantitative phenotypes for bipolar disorder through the use of the Temperament and Character Inventory (TCI), which assesses personality in seven dimensions. Four temperament dimensions are assessed: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (PS). Three character dimensions are also included: self-directedness (SD), cooperativeness (CO), and self-transcendence (ST). We compared personality scores between diagnostic groups and assessed heritability in a sample of 101 families collected for genetic studies of BD. A genome-wide SNP linkage analysis was then performed in the subset of 51 families for which genetic data was available. Significant group differences were observed between BD subjects, their first-degree relatives, and independent controls for all but RD and PS, and all but HA and RD were found to be significantly heritable in this sample. Linkage analysis of the heritable dimensions produced several suggestive linkage peaks for NS (chromosomes 7q21 and 10p15), PS (chromosomes 6q16, 12p13, and 19p13), and SD (chromosomes 4q35, 8q24, and 18q12). The relatively small size of our linkage sample likely limited our ability to reach genome-wide significance in this study. While not genome-wide significant, these results suggest that aspects of personality may prove useful in the identification of genes underlying BD susceptibility. © 2013 Elsevier B.V. All rights reserved.

An AFLP genetic linkage map of pacific abalone ( Haliotis discus hannai)

NASA Astrophysics Data System (ADS)

Qi, Li; Yanhong, Xu; Ruihai, Yu; Akihiro, Kijima

2007-07-01

A genetic linkage map of Pacific abalone ( Haliotis discus hannai) was constructed using AFLP markers based on a two-way pseudo-testeross strategy in a full-sib family. With 33 primer combinations, a total of 455 markers (225 from the female parent and 230 from the male parent) segregated in a 1:1 ratio, corresponding to DNA polymorphism: heterozygous in one parent and null in the other. The female framework map consisted of 174 markers distributed in 18 linkage groups, equivalent to the H. discus hannai haploid chromosome number, and spanning a total length of 2031.4 cM, with an average interval of 13.0 cM between adjacent markers. The male framework map consisted of 195 markers mapped on 19 linkage groups, spanning a total length of 2273.4 cM, with an average spacing of 12.9 cM between adjacent markers. The estimated coverage for the framework linkage maps was 81.2% for the female and 82.1% for the male, on the basis of two estimates of genome length. Fifty-two markers (11.4%) remained unlinked. The level of segregation distortion observed in this cross was 20.4%. These linkage maps will serve as a starting point for linkage studies in the Pacific abalone with potential application for marker-assisted selection in breeding programs.

A population-based study of familial Alzheimer disease: Linkage to chromosomes 14, 19, and 21

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duijn, C.M. van; Hofman, A.; Hendriks, L.

1994-10-01

Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was at or before age 65 years, the mean age at onset was after age 65 years in four families (referred to as {open_quotes}LOAD{close_quotes}). Among the six families with early-onset AD (referred to as {open_quotes}EOAD,{close_quotes} i.e., mean age of onset of AD of relatives was at or before agemore » 65 years), conclusive linkage to 14q24.3 was found in one family with a very early onset (around 47 years), while linkage to the same region was excluded in two other families. For the LOAD families, predominantly negative lod scores were obtained, and the overall lod score excluded linkage to chromosome 14. The results with markers on chromosome 19 and chromosome 21 were not conclusive for EOAD and LOAD. The findings of our study confirm genetic heterogeneity within familial EOAD. 50 refs., 7 figs., 2 tabs.« less

Deflection Analysis of the Space Shuttle External Tank Door Drive Mechanism

NASA Technical Reports Server (NTRS)

Tosto, Michael A.; Trieu, Bo C.; Evernden, Brent A.; Hope, Drew J.; Wong, Kenneth A.; Lindberg, Robert E.

2008-01-01

Upon observing an abnormal closure of the Space Shuttle s External Tank Doors (ETD), a dynamic model was created in MSC/ADAMS to conduct deflection analyses of the Door Drive Mechanism (DDM). For a similar analysis, the traditional approach would be to construct a full finite element model of the mechanism. The purpose of this paper is to describe an alternative approach that models the flexibility of the DDM using a lumped parameter approximation to capture the compliance of individual parts within the drive linkage. This approach allows for rapid construction of a dynamic model in a time-critical setting, while still retaining the appropriate equivalent stiffness of each linkage component. As a validation of these equivalent stiffnesses, finite element analysis (FEA) was used to iteratively update the model towards convergence. Following this analysis, deflections recovered from the dynamic model can be used to calculate stress and classify each component s deformation as either elastic or plastic. Based on the modeling assumptions used in this analysis and the maximum input forcing condition, two components in the DDM show a factor of safety less than or equal to 0.5. However, to accurately evaluate the induced stresses, additional mechanism rigging information would be necessary to characterize the input forcing conditions. This information would also allow for the classification of stresses as either elastic or plastic.

A SSR-based genetic linkage map of cultivated peanut (Arachis hypogaea L.)

USDA-ARS?s Scientific Manuscript database

The objective of this study was to construct a molecular linkage map of cultivated tetraploid 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. Three recombinant inbre...

Map-based molecular diversity, linkage disequilibrium and association mapping of fruit traits in melon

USDA-ARS?s Scientific Manuscript database

The wide phenotypic diversity, in melon fruits, is the result of consumer preferences combined with genotype fitness to the different agro-climatic zones. There is no sufficient information with respect to the extent of genetic divergence, population structure and linkage disequilibrium (LD) in mel...

A first insight into population structure and linkage disequilibrium in the US peanut minicore collection

USDA-ARS?s Scientific Manuscript database

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...

Development and characterization of BAC-end sequence derived SSRs, and their incorporation into a new higher density genetic map for cultivated peanut (Arachis hypogaea L.)

PubMed Central

2012-01-01

Background Cultivated peanut (Arachis hypogaea L.) is an important crop worldwide, valued for its edible oil and digestible protein. It has a very narrow genetic base that may well derive from a relatively recent single polyploidization event. Accordingly molecular markers have low levels of polymorphism and the number of polymorphic molecular markers available for cultivated peanut is still limiting. Results Here, we report a large set of BAC-end sequences (BES), use them for developing SSR (BES-SSR) markers, and apply them in genetic linkage mapping. The majority of BESs had no detectable homology to known genes (49.5%) followed by sequences with similarity to known genes (44.3%), and miscellaneous sequences (6.2%) such as transposable element, retroelement, and organelle sequences. A total of 1,424 SSRs were identified from 36,435 BESs. Among these identified SSRs, dinucleotide (47.4%) and trinucleotide (37.1%) SSRs were predominant. The new set of 1,152 SSRs as well as about 4,000 published or unpublished SSRs were screened against two parents of a mapping population, generating 385 polymorphic loci. A genetic linkage map was constructed, consisting of 318 loci onto 21 linkage groups and covering a total of 1,674.4 cM, with an average distance of 5.3 cM between adjacent loci. Two markers related to resistance gene homologs (RGH) were mapped to two different groups, thus anchoring 1 RGH-BAC contig and 1 singleton. Conclusions The SSRs mined from BESs will be of use in further molecular analysis of the peanut genome, providing a novel set of markers, genetically anchoring BAC clones, and incorporating gene sequences into a linkage map. This will aid in the identification of markers linked to genes of interest and map-based cloning. PMID:22260238

Genetic dissection of seed oil and protein content and identification of networks associated with oil content in Brassica napus

PubMed Central

Chao, Hongbo; Wang, Hao; Wang, Xiaodong; Guo, Liangxing; Gu, Jianwei; Zhao, Weiguo; Li, Baojun; Chen, Dengyan; Raboanatahiry, Nadia; Li, Maoteng

2017-01-01

High-density linkage maps can improve the precision of QTL localization. A high-density SNP-based linkage map containing 3207 markers covering 3072.7 cM of the Brassica napus genome was constructed in the KenC-8 × N53-2 (KNDH) population. A total of 67 and 38 QTLs for seed oil and protein content were identified with an average confidence interval of 5.26 and 4.38 cM, which could explain up to 22.24% and 27.48% of the phenotypic variation, respectively. Thirty-eight associated genomic regions from BSA overlapped with and/or narrowed the SOC-QTLs, further confirming the QTL mapping results based on the high-density linkage map. Potential candidates related to acyl-lipid and seed storage underlying SOC and SPC, respectively, were identified and analyzed, among which six were checked and showed expression differences between the two parents during different embryonic developmental periods. A large primary carbohydrate pathway based on potential candidates underlying SOC- and SPC-QTLs, and interaction networks based on potential candidates underlying SOC-QTLs, was constructed to dissect the complex mechanism based on metabolic and gene regulatory features, respectively. Accurate QTL mapping and potential candidates identified based on high-density linkage map and BSA analyses provide new insights into the complex genetic mechanism of oil and protein accumulation in the seeds of rapeseed. PMID:28393910

Groundwater quality, age, and susceptibility and vulnerability to nitrate contamination with linkages to land use and groundwater flow, Upper Black Squirrel Creek Basin, Colorado, 2013

USGS Publications Warehouse

Wellman, Tristan P.; Rupert, Michael G.

2016-03-03

The results of this investigation offer the foundational information needed for developing best management practices to mitigate nitrate contamination, basic concepts on water quality to aid public education, and information to guide regulatory measures if policy makers determine this is warranted. Science-based decision making will require continued monitoring and analysis of water quality in the future.

Polymorphisms in the Estrogen Receptor β (ESR2) Gene Are Associated with Bone Mineral Density in Caucasian Men and Women

PubMed Central

Ichikawa, Shoji; Koller, Daniel L.; Peacock, Munro; Johnson, Michelle L.; Lai, Dongbing; Hui, Siu L.; Johnston, C. Conrad; Foroud, Tatiana M.; Econs, Michael J.

2007-01-01

Context A major determinant of osteoporotic fractures is peak bone mineral density (BMD), which is a highly heritable trait. Recently, we identified significant linkage for hip BMD in premenopausal sister pairs at chromosome 14q (LOD score = 3.5), where the estrogen receptor β gene (ESR2) is located. Objective The objective of the study was to determine whether ESR2 polymorphisms are associated with normal BMD variation. Design This was a population‐based genetic association study, using 11 single nucleotide polymorphisms (SNPs) distributed across the ESR2 gene. Setting The study was conducted at an academic research laboratory and medical center. Patients and Other Participants A total of 411 healthy men (aged 18–61 yr) and 1291 healthy premenopausal women (aged 20–50 yr) living in Indiana participated in the study. Intervention(s) There were no interventions. Main Outcome Measure(s) The main outcome measures were SNP genotype distributions and their association with BMD at the femoral neck and lumbar spine. Results Significant association of spine BMD was found with three SNPs in men and one SNP in women (P ≤ 0.05). The conditional linkage analysis using the ESR2 haplotypes showed that the ESR2 gene accounts for, at most, 18% of the original linkage. Conclusions ESR2 polymorphisms are significantly associated with bone mass in both men and women. However, the ESR2 gene is not entirely responsible for our original linkage, and an additional gene(s) in chromosome 14q contributes to the determination of BMD. PMID:16118344

Evidence of linkage and association on chromosome 20 for late-onset Alzheimer disease.

PubMed

Goddard, Katrina A B; Olson, Jane M; Payami, Haydeh; van der Voet, Monique; Kuivaniemi, Helena; Tromp, Gerard

2004-06-01

Recently, we reported evidence of linkage on chromosome 20 for Alzheimer disease (AD) using a novel statistical approach to incorporate covariates (e.g., age, ApoE genotype) into the analysis. These results suggest that very elderly subjects (>85 years), and individuals who carry an epsilon2 allele at the ApoE locus are more likely to be linked to this candidate region. The region on chromosome 20 includes a strong candidate gene, cystatin C (CST3), which has previously been associated with AD in case-control studies. We investigated these findings further by genotyping additional markers to narrow the candidate region, and to identify evidence of linkage disequilibrium as additional support for a susceptibility locus on chromosome 20. We selected 43 elderly sibships (89 subjects) from the NIMH AD Genetics Initiative based on current age older than 84 years, and identified 129 unrelated control subjects who were older than 84 years from the Oregon Brain Aging Study to conduct linkage and association studies in this region. Fourteen additional markers were evaluated, including 4 markers located within or near CST3. We narrowed the candidate region on chromosome 20 to an 11.8-cM region between markers D20S174 and D20S471, which includes the CST3 candidate gene. In addition, we observed evidence of association for markers located near the CST3 candidate gene, with P values between 0.002 and 0.08 for two-locus haplotypes. These results support the presence of a susceptibility locus for AD in the vicinity of CST3 for very elderly subjects with AD.

Functional analysis of truncated and site-directed mutagenesis dextransucrases to produce different type dextrans.

PubMed

Wang, Chao; Zhang, Hong-Bin; Li, Meng-Qi; Hu, Xue-Qin; Li, Yao

2017-07-01

Dextrans with distinct molecular size and structure are increasingly being used in the food and pharmaceutical industries. Dextran is produced by dextransucrase (DSR, EC2.4.5.1), which is produced by Leuconostoc mesenteroides. DSR belongs to glycosyl hydrolase family (GH70) and synthesizes branched α-glucan (dextran) with both 5% α(1-3) and 95% α(1-6) glycosidic linkages. The DSR gene dex-YG (Genebank, Accession No. DQ345760) was cloned from the wild strain Leuconostoc mesenteroides 0326. This study generated a series of C-terminally truncated variants of dextransucrase and substituting the amino-acid residues in the active site of DSR. With shorter length of DSR, its polysaccharide-synthesizing capability was impaired heavily, whereas oligosaccharide (acting as prebiotics)-synthesizing capability increased significantly, efficiently producing special sizes of dextran. All truncated mutant enzymes were active. Results demonstrated that the catalytic domain dextransucrase was likely in 800 aa or less. Based on the three-dimensional structure model of dextransucrase built through homology modeling methods, the DSR and its mutants with the acceptor substrate of maltose and donor substrate of sucrose were studied by molecular-docking method. Substituting these amino-acid residues significantly affected enzyme activities. Compared with the wild-type dextran, mutant enzymes catalyzed the synthesis of a-glucan with 1-9% α(1-3) and 90-98% α(1-6) branching linkages. Some mutants introduced a small amount of α(1-4) linkages and α(1-2) linkages. This strategy can be effectively used for the rational protein design of dextransucrase. Copyright © 2017 Elsevier Inc. All rights reserved.

Assignment of a gene for autosomal recessive retinitis pigmentosa (RP12) to chromosome 1q31-q32.1 in an inbred and genetically heterogeneous disease population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Soest, S.; Ingeborgh Van Den Born, L.; Bergen, A.A.B.

1994-08-01

Linkage analysis was carried out in a large family segregating for autosomal recessive retinitis pigmentosa (arRP), originating from a genetically isolated population in The Netherlands. Within the family, clinical heterogeneity was observed, with a major section of the family segregating arRP with characteristic para-arteriolar preservation of the retinal pigment epithelium (PPRPE). In the remainder of the arRP patients no PPRPE was found. Initially, all branches of the family were analyzed jointly, and linkage was found between the marker F13B, located at 1q31-q32.1, and RP12 ({Zeta}{sub max} = 4.99 at 8% recombination). Analysis of linkage heterogeneity between five branches of themore » family yielded significant evidence for nonallelic genetic heterogeneity within this family, coinciding with the observed clinical differences. Multipoint analysis, carried out in the branches that showed linkage, favored the locus order 1cen-D1S158-(F13B, RP12)-D1S53-1qter ({Zeta}{sub max} = 9.17). The finding of a single founder allele associated with the disease phenotype supports this localization. This study reveals that even in a large family, apparently segregating for a single disease entity, genetic heterogeneity can be detected and resolved successfully. 35 refs., 5 figs.« less

Genetic diversity, linkage disequilibrium, population structure and construction of a core collection of Prunus avium L. landraces and bred cultivars.

PubMed

Campoy, José Antonio; Lerigoleur-Balsemin, Emilie; Christmann, Hélène; Beauvieux, Rémi; Girollet, Nabil; Quero-García, José; Dirlewanger, Elisabeth; Barreneche, Teresa

2016-02-24

Depiction of the genetic diversity, linkage disequilibrium (LD) and population structure is essential for the efficient organization and exploitation of genetic resources. The objectives of this study were to (i) to evaluate the genetic diversity and to detect the patterns of LD, (ii) to estimate the levels of population structure and (iii) to identify a 'core collection' suitable for association genetic studies in sweet cherry. A total of 210 genotypes including modern cultivars and landraces from 16 countries were genotyped using the RosBREED cherry 6 K SNP array v1. Two groups, mainly bred cultivars and landraces, respectively, were first detected using STRUCTURE software and confirmed by Principal Coordinate Analysis (PCoA). Further analyses identified nine subgroups using STRUCTURE and Discriminant Analysis of Principal Components (DAPC). Several sub-groups correspond to different eco-geographic regions of landraces distribution. Linkage disequilibrium was evaluated showing lower values than in peach, the reference Prunus species. A 'core collection' containing 156 accessions was selected using the maximum length sub tree method. The present study constitutes the first population genetics analysis in cultivated sweet cherry using a medium-density SNP (single nucleotide polymorphism) marker array. We provided estimations of linkage disequilibrium, genetic structure and the definition of a first INRA's Sweet Cherry core collection useful for breeding programs, germplasm management and association genetics studies.

On normality, ethnicity, and missing values in quantitative trait locus mapping

PubMed Central

Labbe, Aurélie; Wormald, Hanna

2005-01-01

Background This paper deals with the detection of significant linkage for quantitative traits using a variance components approach. Microsatellite markers were obtained for the Genetic Analysis Workshop 14 Collaborative Study on the Genetics of Alcoholism data. Ethnic heterogeneity, highly skewed quantitative measures, and a high rate of missing values are all present in this dataset and well known to impact upon linkage analysis. This makes it a good candidate for investigation. Results As expected, we observed a number of changes in LOD scores, especially for chromosomes 1, 7, and 18, along with the three factors studied. A dramatic example of such changes can be found in chromosome 7. Highly significant linkage to one of the quantitative traits became insignificant when a proper normalizing transformation of the trait was used and when analysis was carried out on an ethnically homogeneous subset of the original pedigrees. Conclusion In agreement with existing literature, transforming a trait to ensure normality using a Box-Cox transformation is highly recommended in order to avoid false-positive linkages. Furthermore, pedigrees should be sorted by ethnic groups and analyses should be carried out separately. Finally, one should be aware that the inclusion of covariates with a high rate of missing values reduces considerably the number of subjects included in the model. In such a case, the loss in power may be large. Imputation methods are then recommended. PMID:16451664

Genomewide Scan for Nonsyndromic Cleft Lip and Palate in Multigenerational Indian Families Reveals Significant Evidence of Linkage at 13q33.1-34

PubMed Central

Radhakrishna, Uppala; Ratnamala, Uppala; Gaines, Mathew; Beiraghi, Soraya; Hutchings, David; Golla, Jeffrey; Husain, Syed A.; Gambhir, Prakash S.; Sheth, Jayesh J.; Sheth, Frenny J.; Chetan, Ghati K.; Naveed, Mohammed; Solanki, Jitendra V.; Patel, Uday C.; Master, Dilipkumar C.; Memon, Rafiq; Antonarakis, Gregory S.; Antonarakis, Stylianos E.; Nath, Swapan K.

2006-01-01

Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P, in which the anomaly segregates as an autosomal dominant trait. The phenotype was variable, ranging from unilateral to bilateral CL-P. A genomewide linkage scan that used ∼10,000 SNPs was performed. Nonparametric linkage (NPL) analysis identified 11 genomic regions (NPL>3.5; P<.005) that could potentially harbor CL-P susceptibility variations. Among those, the most significant evidence was for chromosome 13q33.1-34 at marker rs1830756 (NPL=5.57; P=.00024). This was also supported by parametric linkage; MOD score (LOD scores maximized over genetic model parameters) analysis favored an autosomal dominant model. The maximum LOD score was 4.45, and heterogeneity LOD was 4.45 (α=100%). Haplotype analysis with informative crossovers enabled the mapping of the CL-P locus to a region of ∼20.17 cM (7.42 Mb) between SNPs rs951095 and rs726455. Thus, we have identified a novel genomic region on 13q33.1-34 that harbors a high-risk variant for CL-P in these Indian families. PMID:16909398

The Role of Natural Heritage in Rural Development: An Analysis of Economic Linkages in Scotland

ERIC Educational Resources Information Center

Courtney, Paul; Hill, Gary; Roberts, Deborah

2006-01-01

There is growing recognition of the important role played by natural heritage in rural economic development, but limited empirical work as yet to inform this debate. This paper examines the nature and strength of local economic linkages associated with the natural heritage in four case study areas in Scotland, differentiated in terms of their…

A high density integrated genetic linkage map of soybean and the development of a 1,536 Universal Soy Linkage Panel for QTL mapping

USDA-ARS?s Scientific Manuscript database

Single nucleotide polymorphisms (SNPs) are the marker of choice for many researchers due to their abundance and the high-throughput methods available for their multiplex analysis. Only recently have SNP markers been available to researchers in soybean [Glycine max (L.) Merr.] with the release of th...

Computerized analysis and duplication of mandibular motion.

PubMed

Knap, F J; Abler, J H; Richardson, B L

1975-05-01

A new digital system has been devised to analyze and duplicate jaw motion. The arrangement of the electronic system offers a range of versatility which includes graphic as well as numerical data analysis. The duplicator linkage is identical to the sensor linkage which, together with an accurate model transfer system, results in an encouraging level of accuracy in jaw-motion duplication. The data collected from normal subjects should offer some new knowledge in the normal motions of the mandible as well as establish a reference for comparison with abnormal masticatory function.

Individual specific DNA fingerprints from a hypervariable region probe: alpha-globin 3'HVR.

PubMed

Fowler, S J; Gill, P; Werrett, D J; Higgs, D R

1988-06-01

A probe detecting a hypervariable region (HVR) 3' to the alpha globin locus on chromosome 16 has been used to produce DNA fingerprints. Segregation analysis has revealed multiple, randomly dispersed DNA fragments inherited in a Mendelian fashion with minimal allelism and linkage. The fingerprints are highly polymorphic (probability of chance association between random individuals much less than 10(-14]. The probe is, therefore, a powerful discriminating tool: it is envisaged that this probe will have forensic applications, including paternity cases, and will be informative in linkage analysis.

Development of genomic SSR markers for fingerprinting lettuce (Lactuca sativa L.) cultivars and mapping genes.

PubMed

Rauscher, Gilda; Simko, Ivan

2013-01-22

Lettuce (Lactuca sativa L.) is the major crop from the group of leafy vegetables. Several types of molecular markers were developed that are effectively used in lettuce breeding and genetic studies. However only a very limited number of microsattelite-based markers are publicly available. We have employed the method of enriched microsatellite libraries to develop 97 genomic SSR markers. Testing of newly developed markers on a set of 36 Lactuca accession (33 L. sativa, and one of each L. serriola L., L. saligna L., and L. virosa L.) revealed that both the genetic heterozygosity (UHe = 0.56) and the number of loci per SSR (Na = 5.50) are significantly higher for genomic SSR markers than for previously developed EST-based SSR markers (UHe = 0.32, Na = 3.56). Fifty-four genomic SSR markers were placed on the molecular linkage map of lettuce. Distribution of markers in the genome appeared to be random, with the exception of possible cluster on linkage group 6. Any combination of 32 genomic SSRs was able to distinguish genotypes of all 36 accessions. Fourteen of newly developed SSR markers originate from fragments with high sequence similarity to resistance gene candidates (RGCs) and RGC pseudogenes. Analysis of molecular variance (AMOVA) of L. sativa accessions showed that approximately 3% of genetic diversity was within accessions, 79% among accessions, and 18% among horticultural types. The newly developed genomic SSR markers were added to the pool of previously developed EST-SSRs markers. These two types of SSR-based markers provide useful tools for lettuce cultivar fingerprinting, development of integrated molecular linkage maps, and mapping of genes.

Development of genomic SSR markers for fingerprinting lettuce (Lactuca sativa L.) cultivars and mapping genes

PubMed Central

2013-01-01

Background Lettuce (Lactuca sativa L.) is the major crop from the group of leafy vegetables. Several types of molecular markers were developed that are effectively used in lettuce breeding and genetic studies. However only a very limited number of microsattelite-based markers are publicly available. We have employed the method of enriched microsatellite libraries to develop 97 genomic SSR markers. Results Testing of newly developed markers on a set of 36 Lactuca accession (33 L. sativa, and one of each L. serriola L., L. saligna L., and L. virosa L.) revealed that both the genetic heterozygosity (UHe = 0.56) and the number of loci per SSR (Na = 5.50) are significantly higher for genomic SSR markers than for previously developed EST-based SSR markers (UHe = 0.32, Na = 3.56). Fifty-four genomic SSR markers were placed on the molecular linkage map of lettuce. Distribution of markers in the genome appeared to be random, with the exception of possible cluster on linkage group 6. Any combination of 32 genomic SSRs was able to distinguish genotypes of all 36 accessions. Fourteen of newly developed SSR markers originate from fragments with high sequence similarity to resistance gene candidates (RGCs) and RGC pseudogenes. Analysis of molecular variance (AMOVA) of L. sativa accessions showed that approximately 3% of genetic diversity was within accessions, 79% among accessions, and 18% among horticultural types. Conclusions The newly developed genomic SSR markers were added to the pool of previously developed EST-SSRs markers. These two types of SSR-based markers provide useful tools for lettuce cultivar fingerprinting, development of integrated molecular linkage maps, and mapping of genes. PMID:23339733

Analysis of ethnic disparities in workers' compensation claims using data linkage.

PubMed

Friedman, Lee S; Ruestow, Peter; Forst, Linda

2012-10-01

The overall goal of this research project was to assess ethnic disparities in monetary compensation among construction workers injured on the job through the linkage of medical records and workers' compensation data. Probabilistic linkage of medical records with workers' compensation claim data. In the final multivariable robust regression model, compensation was $5824 higher (P = 0.030; 95% confidence interval: 551 to 11,097) for white non-Hispanic workers than for other ethnic groups when controlling for injury severity, affected body region, type of injury, average weekly wage, weeks of temporary total disability, percent permanent partial disability, death, or attorney use. The analysis indicates that white non-Hispanic construction workers are awarded higher monetary settlements despite the observation that for specific injuries the mean temporary total disability and permanent partial disability were equivalent to or lower than those in Hispanic and black construction workers.

Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

PubMed Central

Wicks, J

2000-01-01

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs. PMID:10788332

Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

PubMed

Wicks, J

2000-06-01

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs.

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

PubMed Central

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 associated with lipid phenotypes in linkage regions on chromosomes 2 and 11. PMID:25819087

Linkage localization of the thoraco-abdominal syndrome (TAS) gene to Xq25-26.

PubMed

Parvari, R; Weinstein, Y; Ehrlich, S; Steinitz, M; Carmi, R

1994-02-15

The thoraco-abdominal syndrome (TAS) presents a closure defect confined to the ventral midline, manifested as ventral hernia of various degrees in all affected individuals and antero-lateral diaphragmatic defect manifested almost exclusively in affected males. The syndrome is inherited as an X-linked dominant trait affecting blastogenesis (XLB mutation). We studied 27 members of the TAS family for linkage on the X chromosome. The best lod score of 5.5 at theta 0.04 was found for the HPRT locus on Xq26.1. A multilocus lod score of 12.4 was observed when the linkage analysis utilized additional markers in Xq25-26.

Genomic Characterization of DArT Markers Based on High-Density Linkage Analysis and Physical Mapping to the Eucalyptus Genome

PubMed Central

Petroli, César D.; Sansaloni, Carolina P.; Carling, Jason; Steane, Dorothy A.; Vaillancourt, René E.; Myburg, Alexander A.; da Silva, Orzenil Bonfim; Pappas, Georgios Joannis; Kilian, Andrzej; Grattapaglia, Dario

2012-01-01

Diversity Arrays Technology (DArT) provides a robust, high throughput, cost-effective method to query thousands of sequence polymorphisms in a single assay. Despite the extensive use of this genotyping platform for numerous plant species, little is known regarding the sequence attributes and genome-wide distribution of DArT markers. We investigated the genomic properties of the 7,680 DArT marker probes of a Eucalyptus array, by sequencing them, constructing a high density linkage map and carrying out detailed physical mapping analyses to the Eucalyptus grandis reference genome. A consensus linkage map with 2,274 DArT markers anchored to 210 microsatellites and a framework map, with improved support for ordering, displayed extensive collinearity with the genome sequence. Only 1.4 Mbp of the 75 Mbp of still unplaced scaffold sequence was captured by 45 linkage mapped but physically unaligned markers to the 11 main Eucalyptus pseudochromosomes, providing compelling evidence for the quality and completeness of the current Eucalyptus genome assembly. A highly significant correspondence was found between the locations of DArT markers and predicted gene models, while most of the 89 DArT probes unaligned to the genome correspond to sequences likely absent in E. grandis, consistent with the pan-genomic feature of this multi-Eucalyptus species DArT array. These comprehensive linkage-to-physical mapping analyses provide novel data regarding the genomic attributes of DArT markers in plant genomes in general and for Eucalyptus in particular. DArT markers preferentially target the gene space and display a largely homogeneous distribution across the genome, thereby providing superb coverage for mapping and genome-wide applications in breeding and diversity studies. Data reported on these ubiquitous properties of DArT markers will be particularly valuable to researchers working on less-studied crop species who already count on DArT genotyping arrays but for which no reference genome is yet available to allow such detailed characterization. PMID:22984541

Linking product-elicited emotional associations and sensory perceptions through a circumplex model based on valence and arousal: Five consumer studies.

PubMed

Jaeger, Sara R; Spinelli, Sara; Ares, Gastón; Monteleone, Erminio

2018-07-01

Sensory product characterisation by consumers is increasingly supplemented by measurement of emotional associations. However, studies that link products' sensory perception and emotional associations are still scarce. Five consumer studies were conducted using cashew nuts, peanuts, chocolate, fruit and processed tomatoes as the product categories. Consumers (n = 685) completed check-all-that-apply (CATA) questions to obtain sensory product perceptions and associations with emotion words. The latter were conceptualised and interpreted through a circumplex emotion model spanned by the dimensions of valence (pleasure to displeasure) and arousal (activation to deactivation). Through regression analysis, sensory terms were mapped to the circumplex model to represent statistical linkages with emotion words. Within a were interpretable. The most notable finding was the highly study-specific nature of the linkages, which was mainly attributed to the influence of product category. Methodological choices may also have been partly responsible for the differences. Three studies used a general emotion vocabulary (EsSense Profile®) and an identical number of sensory terms (n = 39). The less complete coverage of the emotional circumplex and the presence of synonymous sensory terms could have diminished the ability to interpret the results. Conversely, two studies used fewer emotion words and sensory terms and these, furthermore, were purposefully selected for the focal sets of samples. The linkages in these latter studies were more interpretable and this could suggest that customised vocabularies of modest length may be desirable when seeking to establish linkages between emotional associations and sensory characteristics of food/beverage stimuli. Purposeful inclusion of emotion words that fully span the circumplex emotion model may also be desirable. Overall, the research represents a new method for establishing linkages between the sensory properties and emotional association to food and beverage products. Copyright © 2018 Elsevier Ltd. All rights reserved.