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Significant Linkage (significant + linkage)
Terms modified by Significant Linkage Selected AbstractsWhole-Genome Scan for Linkage to Bone Strength and Structure in Inbred Fischer 344 and Lewis Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Imranul Alam Abstract A genome-wide genetic linkage analysis identified several chromosomal regions influencing bone strength and structure in F2 progeny of Fischer 344 x Lewis inbred rats. Introduction: Inbred Fischer 344 (F344) and Lewis (LEW) rats are similar in body size, but the F344 rats have significantly lower BMD and biomechanical strength of the femur and spine compared with LEW rats. The goal of this study was to identify quantitative trait loci (QTL) linked to bone strength and structure in adult female F2 rats from F344 and LEW progenitors. Materials and Methods: The 595 F2 progeny from F344 x LEW rats were phenotyped for measures of bone strength (ultimate force {Fu}; energy to break {U}; stiffness {S}) of the femur and lumbar vertebra and structure (femur midshaft polar moment of inertia {Ip}; femur midshaft cortical area; vertebral area). A genome-wide scan was completed in the F2 rats using 118 microsatellite markers at an average interval of 20 cM. Multipoint quantitative linkage analysis was performed to identify chromosomal regions that harbor QTL for bone strength and structure phenotypes. Results: Evidence of linkage for femur and lumbar strength was observed on chromosomes (Chrs) 1, 2, 5, 10, and 19. Significant linkage for femoral structure was detected on Chrs 2, 4, 5, 7, and 15. QTLs affecting femoral strength on Chrs 2 and 5 were also found to influence femur structure. Unique QTLs on Chrs 1, 10, and 19 were found that contributed to variability in bone strength but had no significant effect on structure. Also, unique QTLs were observed on Chrs 4, 7, and 15 that affected only bone structure without any effect on biomechanics. Conclusion: We showed multiple genetic loci influencing bone strength and structure in F344 x LEW F2 rats. Some of these loci are homologous to mouse and human chromosomes previously linked to related bone phenotypes. [source] Inter-Firm Linkages and Profitability in the Automobile Industry: The Implications for Supply Chain ManagementJOURNAL OF SUPPLY CHAIN MANAGEMENT, Issue 1 2001Harri Ramcharran SUMMARY The current studies on supply chain management are limited in their analysis of the linkages between firms in related industries. This study estimates the degree of linkages between automotive parts suppliers and automobile manufacturers. Significant linkages are demonstrated by the high correlation coefficients of the P/E ratio of auto parts suppliers and auto manufacturers and by the results of regression analysis. Demand uncertainty in the automobile manufacturing industry, resulting from business cycles and unexpected labor disputes, is one of the major risks facing auto parts suppliers. Risk assessment, utilizing information on linkages, is important for demand management and developing profit-maximizing strategies. [source] The heterogeneity of causes and courses of attention-deficit/hyperactivity disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2009H-C. Steinhausen Objective:, Attention-deficit / Hyperactivity Disorder (ADHD) is a frequent mental disorder with onset in childhood and persistence into adulthood in a sizeable number of people. Despite a rather simple clinical definition, ADHD has many facets because of frequent co-morbid disorders and varying impact on psychosocial functioning. Thus, there is considerable heterogeneity in various domains. Method:, A review of recent research findings in: i) selected domains of aetiology reflecting the role of genes, brain structures and functioning and the interplay of causal factors and ii) clinical heterogeneity in terms of co-morbidities, gender effects, courses and outcomes. Results:, Molecular genetic studies have identified a number of candidate genes which have a small effect on behavioural variation in ADHD. In the most recent Genome Scan Meta Analysis of seven ADHD linkage studies, genome-wide significant linkage was identified on chromosome 16. The volume of both the total brain and various regions including the prefrontal cortex, the caudate nucleus and the vermis of the cerebellum is smaller in ADHD. Functional MRI has documented a specific deficit of frontostriatal networks in ADHD. Integrative aetiological models have to take the interaction of gene and environment on various dysfunctions into account. Clinical heterogeneity results from frequent associations with various co-morbidities, the impact of the disorder on psychosocial functioning, and gender effects. Partly, these effects are evident also in the course and outcome of ADHD. Conclusion:, ADHD is a chronic mental disorder with a complex aetiology. So far, various neurobiological factors have been identified that need to be studied further to better understand their interaction with environmental factors. The clinical presentation and the long-term course of ADHD are manifold. [source] A multiple splitting approach to linkage analysis in large pedigrees identifies a linkage to asthma on chromosome 12GENETIC EPIDEMIOLOGY, Issue 3 2009Céline Bellenguez Abstract Large genealogies are potentially very informative for linkage analysis. However, the software available for exact non-parametric multipoint linkage analysis is limited with respect to the complexity of the families it can handle. A solution is to split the large pedigrees into sub-families meeting complexity constraints. Different methods have been proposed to "best" split large genealogies. Here, we propose a new procedure in which linkage is performed on several carefully chosen sub-pedigree sets from the genealogy instead of using just a single sub-pedigree set. Our multiple splitting procedure capitalizes on the sensitivity of linkage results to family structure and has been designed to control computational feasibility and global type I error. We describe and apply this procedure to the extreme case of the highly complex Hutterite pedigree and use it to perform a genome-wide linkage analysis on asthma. The detection of a genome-wide significant linkage for asthma on chromosome 12q21 illustrates the potential of this multiple splitting approach. Genet. Epidemiol. 2009. © 2008 Wiley-Liss, Inc. [source] Limits of fine-mapping a quantitative traitGENETIC EPIDEMIOLOGY, Issue 2 2003Larry D. Atwood Abstract Once a significant linkage is found, an important goal is reducing the error in the estimated location of the linked locus. A common approach to reducing location error, called fine-mapping, is the genotyping of additional markers in the linked region to increase the genetic information. The utility of fine-mapping for quantitative trait linkage analysis is largely unknown. To explore this issue, we performed a fine-mapping simulation in which the region containing a significant linkage at a 10-centiMorgan (cM) resolution was fine-mapped at 2, 1, and 0.5 cM. We simulated six quantitative trait models in which the proportion of variation due to the quantitative trait locus (QTL) ranged from 0.20,0.90. We used four sampling designs that were all combinations of 100 and 200 families of sizes 5 and 7. Variance components linkage analysis (Genehunter) was performed until 1,000 replicates were found with a maximum lodscore greater than 3.0. For each of these 1,000 replications, we repeated the linkage analysis three times: once for each of the fine-map resolutions. For the most realistic model, reduction in the average location error ranged from 3,15% for 2-cM fine-mapping and from 3,18% for 1-cM fine-mapping, depending on the number of families and family size. Fine-mapping at 0.5 cM did not differ from the 1-cM results. Thus, if the QTL accounts for a small proportion of the variation, as is the case for realistic traits, fine-mapping has little value. Genet Epidemiol 24:99,106, 2003. © 2003 Wiley-Liss, Inc. [source] Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium,,HUMAN MUTATION, Issue 2 2007Arjan P.M. de Brouwer Abstract The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes. For 42% of the families with obligate female carriers, the mental retardation phenotype could be explained by a mutation. There was no difference between families with (lod score >2) or without (lod score <2) significant linkage to the X chromosome. For families with two to five affected brothers (brother pair=BP families) only 17% of the MR could be explained. This is significantly lower (P=0.0067) than in families with obligate carrier females and indicates that the MR in about 40% (17/42) of the BP families is due to a single genetic defect on the X chromosome. The mutation frequency of XLMR genes in BP families is lower than can be expected on basis of the male to female ratio of patients with MR or observed recurrence risks. This might be explained by genetic risk factors on the X chromosome, resulting in a more complex etiology in a substantial portion of XLMR patients. The EuroMRX effort is the first attempt to unravel the molecular basis of cognitive dysfunction by large-scale approaches in a large patient cohort. Our results show that it is now possible to identify 42% of the genetic defects in non-syndromic and syndromic XLMR families with obligate female carriers. © 2007 Wiley-Liss, Inc. [source] Association of a melanocortin 4 receptor (MC4R) polymorphism with performance traits in Lithuanian White pigsJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 1 2006R. Jokubka Summary The melanocortin 4 receptor is expressed in virtually all brain regions of mammals and plays an important role in energy homeostasis. Polymorphisms in this gene may thus be related to growth and obesity. In pigs, a non-synonymous polymorphic site was described (Asp298Asn) and demonstrated to affect cAMP production and to alter adenylyl cyclase signalling. Association studies revealed significant linkage of this mutation with production trait in pigs. In this study, 207 Lithuanian White pigs were genotyped at the MC4R locus and analysed on relationships between genotype and breeding values for several performance traits. The observed allele and genotype frequencies did not deviate significantly from Hardy,Weinberg equilibrium (wildtype allele 0.59; mutant allele 0.41) and are comparable with those described in other Large White populations. The mutant Asn298 allele of the MC4R gene was significantly associated with increased test daily gain, higher lean meat percentage and lower backfat thickness. There was a trend towards an improved feed conversion ratio (p = 0.065) in animals with the mutant allele whereas no significant effect was found on lifetime daily gain. These results indicate that the MC4R polymorphism should be integrated in selection programmes in the Lithuanian White to improve carcass composition. [source] A Bivariate Whole Genome Linkage Study Identified Genomic Regions Influencing Both BMD and Bone Structure,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2008Xiao-Gang Liu Abstract Areal BMD (aBMD) and areal bone size (ABS) are biologically correlated traits and are each important determinants of bone strength and risk of fractures. Studies showed that aBMD and ABS are genetically correlated, indicating that they may share some common genetic factors, which, however, are largely unknown. To study the genetic factors influencing both aBMD and ABS, bivariate whole genome linkage analyses were conducted for aBMD-ABS at the femoral neck (FN), lumbar spine (LS), and ultradistal (UD)-forearm in a large sample of 451 white pedigrees made up of 4498 individuals. We detected significant linkage on chromosome Xq27 (LOD = 4.89) for LS aBMD-ABS. In addition, we detected suggestive linkages at 20q11 (LOD = 3.65) and Xp11 (LOD = 2.96) for FN aBMD-ABS; at 12p11 (LOD = 3.39) and 17q21 (LOD = 2.94) for LS aBMD-ABS; and at 5q23 (LOD = 3.54), 7p15 (LOD = 3.45), Xq27 (LOD = 2.93), and 12p11 (LOD = 2.92) for UD-forearm aBMD-ABS. Subsequent discrimination analyses indicated that quantitative trait loci (QTLs) at 12p11 and 17q21 may have pleiotropic effects on aBMD and ABS. This study identified several genomic regions that may contain QTLs important for both aBMD and ABS. Further endeavors are necessary to follow these regions to eventually pinpoint the genetic variants affecting bone strength and risk of fractures. [source] Genetic loci influencing natural variations in femoral bone morphometry in mice,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2001Thomas A. Drake This study identifies genetic loci affecting femoral bone length and width measures in mature mice. Sixteen month old female F2 progeny of a C57BL/6J and DBA/2J intercross were examined for femur length and width of the femoral head, intertrochanteric region and three locations of the diaphysis using digitized images of femur radiographs obtained in the anterior-posterior and lateral projections. A genome wide linkage map was constructed using microsatellite markers at an average density of 20 cM, and quantitative trait locus analysis used to identify regions of the genome showing linkage with the traits measured. Femur length showed significant linkage with loci on proximal chromosome 3 (lod 6.1), and suggestive linkage with a locus on chromosome 14. A major locus on mid-chromosome 7 controlled width of the diaphysis (lod 6.8). Other loci were identified on chromosomes 2 and 4. Width at the intertrochanteric region had suggestive linkage with loci on chromosomes 6 and 19. No loci were found with linkage for width of the femoral head. Candidate genes related to bone development or metabolism are present at most of these loci. These findings show that genetic regulation of femoral bone morphology is complex, and are consistent with the distinct biologic processes that control longitudinal and lateral growth of the femur. © 2001 Orthopaedic Research Society. Punlished by Elsevier Science Ltd. All rights reserved. [source] Genetic heterogeneity in rheumatoid arthritis mouse models induced by extrinsic and intrinsic factorsPATHOLOGY INTERNATIONAL, Issue 6 2010Shinichi Mizuki A cumulative effect of the susceptibility genes with polymorphic alleles may be responsible for rheumatoid arthritis (RA). The objective of this study was to clarify whether susceptibility to RA is under the control of common allelic loci between two different RA models induced by extrinsic and intrinsic factors, collagen-induced arthritis (CIA) in DBA/1 mice and arthritis in MRL/Mp (MRL) mice associated with the Fas deficient mutant gene, Faslpr, respectively. CIA was examined in mice of parental DBA/1 and MRL, (MRL × DBA/1) F1 and (MRL × DBA/1) F2 progenies. In genome-wide screening of the severity in the F2 using microsatellite markers, significant linkage was observed on chromosomes 5 and 17 at map position of D5Mit259 and H-2, respectively, associated with DBA/1 alleles, while there was no loci associated with arthritis of MRL- Faslpr mice previously identified. In a quantitative trait locus (QTL) analysis, the locus on chromosome 5 showed the highest peak at map position 35 cM (LOD score 6.0). This study may indicate that the arthritis induced by extrinsic and intrinsic factors is under the control of a different combination of susceptibility genes with common and different alleles, possibly simulating the genetic heterogeneity of RA. [source] Evidence for the multigenic inheritance of schizophreniaAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 8 2001Robert Freedman Abstract Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z,=,3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the ,7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z,=,2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci. © 2001 Wiley-Liss, Inc. [source] Whole-genome scan for guttural pouch tympany in Arabian and German warmblood horsesANIMAL GENETICS, Issue 6 2009A. Zeitz Summary Equine guttural pouch tympany (GPT) is a hereditary disease in foals of several breeds, including thoroughbreds, Arabian, Quarter and warmblood horses. We performed a whole-genome scan for GPT in 143 horses from five Arabian and five German warmblood families and genotyped 257 microsatellites. Chromosome-wide significant linkage was detected on ECA2 and ECA15 using multipoint non-parametric linkage analyses. Analyses stratified by sex revealed chromosome-wide significant linkage on ECA2 for fillies and chromosome-wide significant linkage on ECA15 for colts. For Arabian colts, the quantitative trait locus (QTL) on ECA15 was genome-wide significant. Haplotypes including two to four microsatellites within the QTL on ECA2 and 15 in fillies and colts, respectively, were significantly associated with GPT for both breeds. Thus, our analysis indicated sex-specific QTL, a fact which is in agreement with a two- to fourfold higher incidence of GPT in females. This is the first report of QTL for equine GPT and a first step towards identifying genes responsible for GPT. [source] Assignment of 128 genes localized on human chromosome 14q to the IMpRH mapANIMAL GENETICS, Issue 4 2009T. Shimogiri Summary To provide a gene-based comparative map and to examine a porcine genome assembly using bacterial artificial chromosome-based sequence, we have attempted to assign 128 genes localized on human chromosome 14q (HSA14q) to a porcine 7000-rad radiation hybrid (IMpRH) map. This study, together with earlier studies, has demonstrated the following. (i) 126 genes were incorporated into two SSC7 RH linkage groups by CarthaGene analysis. (ii) In the remaining two genes, TOX4 linked to TCRA located in SSC7 by two-point analysis, whereas SIP1 showed no significant linkage with any gene/marker registered in the IMpRH Web Server. (iii) In the two groups, the gene clusters located from 19.9 to 36.5 Mb on HSA14q11.2-q13.3 and from 64.0 to 104.3 Mb on HSA14q23-q32.33 respectively were assigned to SSC7q21-q26. (iv) Comparison of the gene order between the present RH map and the latest porcine sequence assembly revealed some inconsistencies, and a redundant arrangement of 16 genes in the sequence assembly. [source] Nonlinear Cointegration Relationships Between Non-Life Insurance Premiums and Financial MarketsJOURNAL OF RISK AND INSURANCE, Issue 3 2009Fredj Jawadi The aim of this article is to study the adjustment dynamics of the non-life insurance premium (NLIP) and test its dependence to the financial markets in five countries (Canada, France, Japan, the United Kingdom, and the United States). First, we justify the linkage between the insurance and the financial markets by the underwriting cycle theory and financial models of insurance pricing. Second, we examine the relationship between the NLIP, the interest rate, and the stock price using the recent developments of nonlinear econometrics. We use threshold cointegration models: the switching transition error correction models (STECM). We show that STECM perform better than a linear error correction model (LECM) to reproduce the NLIP dynamics. Our empirical results show that the adjustment of the NLIP in France, Japan, and the United States is rather discontinuous, asymmetrical, and nonlinear. Moreover, we suggest a strong evidence of significant linkages between insurance and financial markets, show two regimes for the NLIP, and find that the NLIP adjustment toward equilibrium is time varying with a convergence speed that varies according to the insurance disequilibrium size. [source] SME Competitive Strategy and Location Behavior: An Exploratory Study of High-Technology ManufacturingJOURNAL OF SMALL BUSINESS MANAGEMENT, Issue 2 2008Craig S. Galbraith Forty-four Scottish small and medium-sized high-technology manufacturing firms were surveyed regarding their technology strategies and the impact of regional- and site-specific infrastructure requirements on their location behavior. An empirically derived typology of technology content for high-technology firms was developed via cluster analysis and utilized, together with selected technology and manufacturing strategy variables, to investigate whether significant linkages existed between these variables and firms' related location decisions. Results suggest that location decisions are directly correlated to a firm's competitive strategy and that they should actually be considered a dynamic dimension of strategy rather than a static one-time choice. [source] Interdependencies between agricultural commodity futures prices on the LIFFETHE JOURNAL OF FUTURES MARKETS, Issue 3 2002P. J. Dawson Interdependencies between commodity prices can arise from the impact of changing macroeconomic variables, from complementarities or substitutabilities between commodities, or from common responses by speculators. Malliaris and Urrutia (1996) found significant linkages between rollover prices of six related agricultural commodities on the Chicago Board of Trade. This article examines interdependencies between futures prices for soft commodities traded on the London International Financial Futures Exchange (LIFFE), calculated using Clark indices. Results show that there are no interdependencies between any two prices; price discovery of one contract provides no information about others. © 2002 John Wiley & Sons, Inc. Jrl Fut Mark 22: 269,280, 2002 [source] Identification of a 3.7-Mb region for a marbling QTL on bovine chromosome 4 by identical-by-descent and association analysisANIMAL GENETICS, Issue 6 2009K. Yokouchi Summary QTL mapping for growth and carcass traits was performed using a paternal half-sib family composed of 325 Japanese Black cattle offspring. Nine QTL were detected at the 1% chromosome-wise significance level at a false discovery rate of less than 0.1. These included two QTL for marbling on BTA 4 and 18, two QTL for carcass weight on BTA 14 and 24, two QTL for longissimus muscle area on BTA 1 and 4, two QTL for subcutaneous fat thickness on BTA 1 and 15 and one QTL for rib thickness on BTA 6. Although the marbling QTL on BTA 4 has been replicated with significant linkages in two Japanese Black cattle sires, the three Q (more marbling) haplotypes, each inherited maternally, were apparently different. To compare the three Q haplotypes in more detail, high-density microsatellite markers for the overlapping regions were developed within the 95% CIs (65 markers in 44,78 cM). A detailed haplotype comparison indicated that a small region (<3.7 Mb) around 46 cM was shared between the Qs of the two sires, whose dams were related. An association of this region with marbling was shown by a regression analysis using the local population, in which the two sires were produced and this was confirmed by an association study using a population collected throughout Japan. These results strongly suggest that the marbling QTL on BTA 4 is located in the 3.7-Mb region at around 46 cM. [source] A metric for corporate environmental indicators , for small and medium enterprises in the PhilippinesBUSINESS STRATEGY AND THE ENVIRONMENT, Issue 1 2009Purba Rao Abstract This paper is an outcome of the empirical research, funded by UNDP Philippines and National Economic Development Authority (NEDA), done to establish and implement a metric of corporate environmental indicators for SMEs in the Philippines. SMEs have always played a vital role in the creation of goods and services in the country. It is therefore imperative that SMEs adhere to safe environment practices so that the greening of industries in this region is consummate. In this research we have considered SMEs operating in the food and beverage, furniture, fashion accessories, hotel and restaurant, automotive parts and electroplating sectors. The metric adopted in this research follows the framework given by the Federal Environmental Ministry in Bonn and the Federal Environmental Agency in Berlin. ,,The empirical approach develops an exploratory analysis and a structural equation model to bring out statistically significant linkages between five latent constructs: environment management indicators, environment performance indicators, environmental performance, business performance and competitiveness. The research hopes to urge SMEs to implement this metric with confidence given that this would not only enhance their environmental performance but also lead to superior business performance and enhanced competitiveness. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment. [source] | ||||||||||||||||