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Disequilibrium Analysis (disequilibrium + analysis)
Kinds of Disequilibrium Analysis Selected AbstractsPopulation genetics of Escherichia coli in a natural population of native Australian ratsENVIRONMENTAL MICROBIOLOGY, Issue 6 2000Gulietta M. Pupo Escherichia coli, a normal inhabitant of the intestinal tract of mammals and birds, is a diverse species. Most studies on E. coli populations involve organisms from humans or human-associated animals. In this study, we undertook a survey of E. coli from native Australian mammals, predominantly Rattus tunneyi, living in a relatively pristine environment in the Bundjalung National Park. The genetic diversity was assessed and compared by multilocus enzyme electrophoresis (MLEE), sequence analysis of the mdh (malate dehydrogenase) gene and biotyping using seven sugars. Ninety-nine electrophoretic types were identified from the 242 isolates analysed by MLEE and 15 sequences from the mdh genes sequenced from 21 representative strains. The Bundjalung isolates extend the diversity represented by the E. coli reference (ECOR) set, with new MLEE alleles found in six out of 10 loci. Many of the Bundjalung isolates fell into a discrete group in MLEE. Other Bundjalung strains fell into the recognized E. coli ECOR set groups, but tended to be at the base of both the MLEE and mdh gene trees, implying that these strains are derived independently from ancestral forms of the ECOR groups and that ECOR strains represent only a subset of E. coli adapted to humans and human-associated animals. Linkage disequilibrium analysis showed that the Bundjalung population has an ,epidemic' population structure. The Bundjalung isolates were able to utilize more sugars than the ECOR strains, suggesting that diet plays a prominent role in adaptation of E. coli. [source] Case-control single-marker and haplotypic association analysis of pedigree dataGENETIC EPIDEMIOLOGY, Issue 2 2005Sharon R. Browning Abstract Related individuals collected for use in linkage studies may be used in case-control linkage disequilibrium analysis, provided one takes into account correlations between individuals due to identity-by-descent (IBD) sharing. We account for these correlations by calculating a weight for each individual. The weights are used in constructing a composite likelihood, which is maximized iteratively to form likelihood ratio tests for single-marker and haplotypic associations. The method scales well with increasing pedigree size and complexity, and is applicable to both autosomal and X chromosomes. We apply the approach to an analysis of association between type 2 diabetes and single-nucleotide polymorphism markers in the PPAR-, gene. Simulated data are used to check validity of the test and examine power. Analysis of related cases has better power than analysis of population-based cases because of the increased frequencies of disease-susceptibility alleles in pedigrees with multiple cases compared to the frequencies of these alleles in population-based cases. Also, utilizing all cases in a pedigree rather than just one per pedigree improves power by increasing the effective sample size. We demonstrate that our method has power at least as great as that of several competing methods, while offering advantages in the ability to handle missing data and perform haplotypic analysis. Genet. Epidemiol. 28:110,122, 2005. © 2004 Wiley-Liss, Inc. [source] D90A- SOD1 mediated amyotrophic lateral sclerosis: A single founder for all cases with evidence for a Cis -acting disease modifier in the recessive haplotype,,HUMAN MUTATION, Issue 6 2002Matthew J. Parton Abstract More than 100 different heterozygous mutations in copper/zinc superoxide dismutase (SOD1) have been found in patients with amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Uniquely, D90A- SOD1 has been identified in recessive, dominant and apparently sporadic pedigrees. The phenotype of homozygotes is stereotyped with an extended survival, whereas that of affected heterozygotes varies. The frequency of D90A- SOD1 is 50 times higher in Scandinavia (2.5%) than elsewhere, though ALS prevalence is not raised there. Our earlier study indicated separate founders for recessive and dominant/sporadic ALS and we proposed a disease-modifying factor linked to the recessive mutation. Here we have doubled our sample set and employed novel markers to characterise the mutation's origin and localise any modifying factor. Linkage disequilibrium analysis indicates that D90A homozygotes and heterozygotes share a rare haplotype and are all descended from a single ancient founder (alpha 0.974) c.895 generations ago. Homozygotes arose subsequently only c.63 generations ago (alpha 0.878). Recombination has reduced the region shared by recessive kindreds to 97-265 kb around SOD1, excluding all neighbouring genes. We propose that a cis -acting regulatory polymorphism has arisen close to D90A- SOD1 in the recessive founder, which decreases ALS susceptibility in heterozygotes and slows disease progression. © 2002 Wiley-Liss, Inc. [source] Fine mapping of a quantitative trait locus on chromosome 9 affecting non-return rate in Swedish dairy cattleJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 5 2007M. Holmberg Summary We previously mapped a quantitative trait locus (QTL) affecting the trait non-return rate at 56 days in heifers to bovine chromosome 9. The purpose of this study was to confirm and refine the position of the QTL by using a denser marker map and fine mapping methods. Five families that previously showed segregation for the QTL were included in the study. The mapping population consisted of 139 bulls in a granddaughter design. All bulls were genotyped for 25 microsatellite markers surrounding the QTL on chromosome 9. We also analysed the correlated trait number of inseminations per service period in heifers. Both traits describe the heifer's ability to become pregnant after insemination. Linkage analysis, linkage disequilibrium and combined linkage and linkage disequilibrium analysis were used to analyse the data. Analysis of the families jointly by linkage analysis resulted in a significant but broad QTL peak for non-return rate. Results from the combined analysis gave a sharp QTL peak with a well-defined maximum in between markers BMS1724 and BM7209, at the same position as where the highest peak from the linkage disequilibrium analysis was found. One of the sire families segregated clearly at this position and the difference in effects between the two sire haplotypes was 2.9 percentage units in non-return rate. No significant results were found for the number of inseminations in the combined analysis. [source] Detecting introgressive hybridization between free-ranging domestic dogs and wild wolves (Canis lupus) by admixture linkage disequilibrium analysisMOLECULAR ECOLOGY, Issue 10 2006A. VERARDI Abstract Occasional crossbreeding between free-ranging domestic dogs and wild wolves (Canis lupus) has been detected in some European countries by mitochondrial DNA sequencing and genotyping unlinked microsatellite loci. Maternal and unlinked genomic markers, however, might underestimate the extent of introgressive hybridization, and their impacts on the preservation of wild wolf gene pools. In this study, we genotyped 220 presumed Italian wolves, 85 dogs and 7 known hybrids at 16 microsatellites belonging to four different linkage groups (plus four unlinked microsatellites). Population clustering and individual assignments were performed using a Bayesian procedure implemented in structure 2.1, which models the gametic disequilibrium arising between linked loci during admixtures, aiming to trace hybridization events further back in time and infer the population of origin of chromosomal blocks. Results indicate that (i) linkage disequilibrium was higher in wolves than in dogs; (ii) 11 out of 220 wolves (5.0%) were likely admixed, a proportion that is significantly higher than one admixed genotype in 107 wolves found previously in a study using unlinked markers; (iii) posterior maximum-likelihood estimates of the recombination parameter r revealed that introgression in Italian wolves is not recent, but could have continued for the last 70 (± 20) generations, corresponding to approximately 140,210 years. Bayesian clustering showed that, despite some admixture, wolf and dog gene pools remain sharply distinct (the average proportions of membership to wolf and dog clusters were Qw = 0.95 and Qd = 0.98, respectively), suggesting that hybridization was not frequent, and that introgression in nature is counteracted by behavioural or selective constraints. [source] Characterization of 18 new microsatellite loci in Atlantic cod (Gadus morhua L.)MOLECULAR ECOLOGY RESOURCES, Issue 6 2008SIGURLAUG SKIRNISDOTTIR Abstract Eighteen new microsatellite loci consisting of 10 di-, 5 tri-, 2 tetra- and 1 heptanucleotide repeats are introduced for the Atlantic cod (Gadus morhua L.). All loci were co-amplified in two polymerase chain reactions (plus two previously published microsatellites) and all products were typed clearly. The number of alleles per locus ranged from six (PGmo130) to 45 (PGmo76) and the observed heterozygosity ranged from 0.356 (PGmo130) to 0.957 (PGmo95). All loci except one followed Hardy,Weinberg expectations. Genetic linkage disequilibrium analysis between all pairs of loci did not yield any significant values. [source] Effect of myostatin F94L on carcass yield in cattleANIMAL GENETICS, Issue 5 2007G. S. Sellick Summary In this study, a highly significant quantitative trait locus (QTL) for meat percentage, eye muscle area (EMA) and silverside percentage was found on cattle chromosome 2 at 0,15 cM, a region containing the positional candidate gene growth differentiation factor 8 (GDF8), which has the common alias myostatin (MSTN). Loss-of-function mutations in the MSTN gene are known to cause an extreme ,double muscling' phenotype in cattle. In this study, highly significant associations of MSTN with cattle carcass traits were found using maternally inherited MSTN haplotypes from outbred Limousin and Jersey cattle in a linkage disequilibrium analysis. A previously reported transversion in MSTN (AF320998.1:g.433C>A), resulting in the amino acid substitution of phenylalanine by leucine at position 94 of the protein sequence (F94L), was the only polymorphism consistently related to increased muscling. Overall, the size of the g.433C>A additive effect on carcass traits was moderately large, with the g.433A allele found to be associated with a 5.5% increase in silverside percentage and EMA and a 2.3% increase in total meat percentage relative to the g.433C allele. The phenotypic effects of the g.433A allele were partially recessive. This study provides strong evidence that a MSTN genotype can produce an intermediate, non-double muscling phenotype, which should be of significant value for beef cattle producers. [source] FMR1 CGG Repeat Patterns and Flanking Haplotypes in Three Asian Populations and Their Relationship With Repeat InstabilityANNALS OF HUMAN GENETICS, Issue 6 2006Youyou Zhou Summary Hyper-expansion of a CGG repeat in the 5, untranslated region of the FMR1 gene followed by methylation and silencing is the predominant cause of Fragile X syndrome, the most common inherited mental retardation disorder. Most detailed studies of the FMR1 gene have focused on Caucasian populations and patients. We performed a detailed haplotype and linkage disequilibrium analysis of the FMR1 gene in a total of 454 unselected normal X chromosomes from three Asian populations, Chinese, Malay and Indian. Compared to Caucasians and African Americans, the diversity of normal FMR1 CGG repeat lengths, patterns and flanking haplotypes were lower in Asians. Strong linkage disequilibrium was observed between the CGG repeat and flanking FMR1 markers in all three Asian populations, with strong association between specific CGG repeat alleles and flanking marker alleles observed only in the Chinese and Malays. A test for randomness of distribution between FRAXA CGG repeat patterns and flanking FMR1 marker haplotypes also revealed a highly significant non-random distribution between CGG repeat patterns and flanking haplotypes in all three ethnic groups (P < 0.001). Extending previous findings in Caucasians and African Americans we present a novel statistical approach, using data from unselected population samples alone, to show an association between absence of at least one AGG interruption in any position (5,, 3,, or middle) and increased CGG repeat instability. [source] Interleukin-1 gene cluster variants with innate cytokine production profiles and osteoarthritis in subjects from the Genetics, Osteoarthritis and Progression StudyARTHRITIS & RHEUMATISM, Issue 4 2010Ingrid Meulenbelt Objective To assess whether genetic variation in the interleukin-1 (IL-1) gene cluster contributes to familial osteoarthritis (OA) by influencing innate ex vivo production of IL-1, or IL-1 receptor antagonist (IL-1Ra). Methods Innate ex vivo IL-1, and IL-1Ra production upon lipopolysaccharide (LPS) stimulation of whole blood cells was measured in subjects from the Genetics, Osteoarthritis and Progression (GARP) Study, which includes sibling pairs in which at least one sibling has symptomatic OA at multiple sites. Radiographic OA (ROA) was assessed by Kellgren/Lawrence score. Subjects from the GARP Study and controls from the Rotterdam Study were genotyped for 7 single-nucleotide polymorphisms (SNPs) encompassing the IL-1 gene cluster on chromosome 2q13. Linkage disequilibrium analysis and genotype and haplotype association analysis were performed to assess the relationship between the IL-1 gene cluster SNPs, innate ex vivo cytokine production, and OA. Results Among subjects in the GARP Study, the haplotype variable-number tandem repeat in intron 2/T+8006C/T+11100C 2/2/1 of the IL1RN gene was significantly associated with reduced innate ex vivo bioavailability of IL-1, upon LPS stimulation (P = 0.026) and with ROA at the highest number of joint locations. Conclusion These results show that genetic variation at the IL-1 gene cluster is associated with lower IL-1, bioavailability and with OA at a large number of joint locations. The data further indicate that, among subjects with OA affecting the highest number of joints, the innate immune system may be activated, thereby obscuring possible underlying mechanisms. [source] Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domainsARTHRITIS & RHEUMATISM, Issue 7 2009Gilberto Vargas-Alarcón Objective Fibromyalgia (FM) patients have signs of relentless sympathetic hyperactivity associated with hyporeactivity to stress. Adrenergic receptors (ARs) are parts of the sympathetic nervous system that are fundamental for maintenance of homeostasis. We undertook this study to correlate ,-AR and ,-AR gene polymorphisms with the presence of FM and with different domains of the FM syndrome as measured by the Fibromyalgia Impact Questionnaire (FIQ). Methods We studied 78 Mexican FM patients and 48 age-matched controls as well as 78 Spanish FM patients and 71 controls. All subjects studied were women. Single-nucleotide polymorphisms (SNPs) of ,1A -AR (rs574584, rs1383914, rs1048101, and rs573542), ,2 -AR (rs1042713 and rs1042714), and ,3 -AR (rs4994) were analyzed by 5, exonuclease TaqMan polymerase chain reaction. Polymorphic haplotypes were constructed after linkage disequilibrium analysis. Results The ,2 -AR AC haplotype was a risk factor for the presence of FM. This haplotype had an increased frequency in Mexican patients compared with Mexican controls (42.1% versus 30.5%; P = 0.04). Similarly, 50.4% of Spanish patients had this haplotype compared with 40.0% of Spanish controls (P = 0.05). In Spanish patients, the ,1A -AR SNP rs1383914 was associated with the presence of FM (P = 0.01), and the ,1A -AR SNP rs1048101 was linked with FIQ disability (P = 0.02). Mexican patients with the rs574584 GG genotype presented the highest FIQ score compared with Mexican patients with other genotypes (P = 0.01), and in Mexicans SNP rs574584 was associated with FIQ morning stiffness (P = 0.04) and with FIQ tiredness upon awakening (P = 0.02). Conclusion AR gene polymorphisms are related to the risk of developing FM and are also linked to different domains of the FM syndrome. [source] | ||||||||||||||||||||||