Distribution by Scientific Domains
Distribution within Life Sciences

Kinds of Disequilibrium

  • complete linkage disequilibrium
  • gametic disequilibrium
  • hardy-weinberg disequilibrium
  • high linkage disequilibrium
  • linkage disequilibrium
  • significant linkage disequilibrium
  • strong linkage disequilibrium

  • Terms modified by Disequilibrium

  • disequilibrium analysis
  • disequilibrium mapping
  • disequilibrium pattern
  • disequilibrium test

  • Selected Abstracts


    EVOLUTION, Issue 4 2003
    Francisco Rodríguez-Trelles
    Abstract Allozyme loci are frequently found non randomly associated to the chromosomal inversions in which they are included in Drosophila. Two opposite views compete to explain strong allozyme-by-inversion gametic disequilibria: they result from natural selection or, conversely, merely represent remnants of associations accidentally established at the origin of inversions. Empirical efforts aimed at deciding between adaptive and historical scenarios have focused on the spatial distribution of disequilibria. Yet, the evolutionary significance of these associations remains uncertain. I report here the results of a time-series analysis of the seasonal variation of alleles at six allozyme loci (Acph, Lap, Pept-1, Ao, Mpi, and Xdh) in connection with the O chromosomal polymorphisms of D. subobscura. The findings were: (1) in the segment I of the O chromosome, Lap and Pept-1 allozymes changed seasonally in a cyclical fashion within the ST gene arrangement, but they changed erratically within the 3+4 gene configuration; (2) the frequencies of Lap111 and Pept-10,40 within ST dropped to their lowest values in early and late summer, respectively, when the seasonal level of the ST arrangement is lowest. Furthermore, Lap1,11 and Pept-10,40 covary with ST only within these seasons, yet in a fashion inconsistent with these alleles having a major influence on the dynamics of the inversion; (3) seasonal cycling of alleles within inversions were not detected at Acph, Ao, Mpi, and Xdh, yet these loci are nearly monomorphic at the study population, and/or their sampled series were shorter than those for Lap and Pept-1; and (4) simply monitoring allozyme frequencies separately for each inversion proved to be superior, for evidencing the seasonal cycles of the disequilibria, to the use of the D' coefficient of association. Observed seasonal cycles of allozymes within inversions likely reflect natural selection. [source]

    Austria's Demand for International Reserves and Monetary Disequilibrium: The Case of a Small Open Economy with a Fixed Exchange Rate Regime

    ECONOMICA, Issue 281 2004
    Harald Badinger
    Using a vector error correction approach, I estimate Austria's demand for international reserves over the period 1985:1,1997:4 and test for short-run effects of the disequilibrium on the national monetary market. I find that Austria's long-run reserve demand can be described as a stable function of imports, uncertainty and the opportunity cost of holding reserves with strong economies of scale. The speed of adjustment takes a value of 38 per cent. The results confirm that an excess of money demand (supply) induces an inflow (outflow) of international reserves as postulated by the monetary approach to the balance of payments. [source]

    Characterization of simple sequence repeat variants linked to candidate genes for behavioral phenotypes,,

    HUMAN MUTATION, Issue 1 2006
    Zoë Prichard
    Abstract Simple sequence repeats (SSRs) have traditionally been used as markers in gene mapping studies and typing for forensic purposes. Recently there has been some speculation that this type of genetic variation also plays a more direct role in influencing gene expression and hence complex phenotypic outcomes such as human behavior. For this reason it is interesting to investigate SSRs linked to candidate genes for various complex phenotypes. An economical multiplex PCR-based assay was designed to simultaneously genotype individuals at 15 loci across 10 candidate genes for human behavioural phenotypes, including seven loci previously unreported in Caucasians (five unreported in any population). All loci were tested for Hardy-Weinberg equilibrium and for two-locus Linkage Disequilibrium. Ewens-Watterson neutrality testing indicated possible selection at a previously unreported DRD2 locus. © 2005 Wiley-Liss, Inc. [source]

    The Impact of Incomplete Linkage Disequilibrium and Genetic Model Choice on the Analysis and Interpretation of Genome-wide Association Studies

    Mark M. Iles
    Summary When conducting a genetic association study, it has previously been observed that a multiplicative risk model tends to fit better at a disease-associated marker locus than at the ungenotyped causative locus. This suggests that, while overall risk decreases as linkage disequilibrium breaks down, non-multiplicative components are more affected. This effect is investigated here, in particular the practical consequences it has on testing for trait/marker associations and the estimation of mode of inheritance and risk once an associated locus has been found. The extreme significance levels required for genome-wide association studies define a restricted range of detectable allele frequencies and effect sizes. For such parameters there is little to be gained by using a test that models the correct mode of inheritance rather than the multiplicative; thus the Cochran-Armitage trend test, which assumes a multiplicative model, is preferable to a more general model as it uses fewer degrees of freedom. Equally when estimating risk, it is likely that a multiplicative risk model will provide a good fit to the data, regardless of the underlying mode of inheritance at the true susceptibility locus. This may lead to problems in interpreting risk estimates. [source]

    Attributing Hardy-Weinberg Disequilibrium to Population Stratification and Genetic Association in Case-Control Studies

    Vaneeta K. Grover
    Summary Loci exhibiting Hardy-Weinberg disequilibrium (HWD) are often excluded from association studies, because HWD may indicate genotyping error, population stratification or selection bias. For case-control studies, HWD can result from a genetic effect at the locus. We extend the modelling to accommodate both stratification and genetic effects. Theoretical genotype frequencies and HWD coefficients are derived under a general genetic model for a population with two strata. Maximum likelihood is used to estimate model parameters and a test for lack of fit identifies the models most consistent with the data. Simulations were used to assess the method. The technique was applied to a group of ethnically and clinically heterogeneous kidney stone formers and controls, both exhibiting HWD for the R990G SNP of the CASR gene. Results indicate the best fitting model incorporates both stratification and genetic association. The ability of our method to apportion HWD to stratification and genetic effects may well be a significant advance in dealing with heterogeneity in case-control genetic association studies. [source]

    Heterogeneous Disease Modeling for Hardy-Weinberg Disequilibrium in Case-Control Studies: Application to Renal Stones and Calcium-Sensing Receptor Polymorphisms

    D. C. Hamilton
    Summary Renal stone formation due to hypercalciuria is a relatively common disorder with clear evidence for genetic predisposition, but cryptic phenotypic heterogeneity has hampered identification of candidate genes. The R990G single-nucleotide polymorphism (SNP) of the calcium sensing receptor (CASR) gene has been associated with hypercalciuria in stone formers and shows the appropriate functional phenotype in cell culture. In our preliminary association analysis of a case-control cohort, however, we observed significant Hardy-Weinberg disequilibrium (HWD) for the cases (n= 223), but not controls (n= 676) at the R990G locus, pointing us toward the general disease model incorporating HWD. Because there is an adjacent CASR SNP, A986S, which is in negative linkage disequilibrium with R990G, we extended the general disease model to enable testing of a two-site hypothesis. In our data set, there is no lack of fit (P= .345) for the single-locus model for the R990G genotype, and likelihood ratio testing favors a recessive effect with an eight-fold increase in risk (P < .001) for GG homozygotes, relative to wild-type, based on a population prevalence of 2%. Addition of the A986S genotype provides no additional information either by itself or when included in our two-site model. [source]

    The Causal Element for the Lactase Persistence/ non-persistence Polymorphism is Located in a 1 Mb Region of Linkage Disequilibrium in Europeans

    M. Poulter
    Summary Expression of lactase in the intestine persists into adult life in some people and not others, and this is due to a cis -acting regulatory polymorphism. Previous data indicated that a mutation leading to lactase persistence had occurred on the background of a 60 kb 11-site LCT haplotype known as A (Hollox et al. 2001). Recent studies reported a 100% correlation of lactase persistence with the presence of the T allele at a CT SNP at ,14 kb from LCT, in individuals of Finnish origin, suggesting that this SNP may be causal of the lactase persistence polymorphism, and also reported a very tight association with a second SNP (GA ,22 kb) (Enattah et al. 2002). Here we report the existence of a one megabase stretch of linkage disequilibrium in the region of LCT and show that the ,14 kb T allele and the ,22 kb A allele both occur on the background of a very extended A haplotype. In a series of Finnish individuals we found a strong correlation (40/41 people) with lactose digestion and the presence of the T allele. The T allele was present in all 36 lactase persistent individuals from the UK (phenotyped by enzyme assay) studied, 31/36 of whom were of Northern European ancestry, but not in 11 non-persistent individuals who were mainly of non-UK ancestry. However, the CT heterozygotes did not show intermediate lactase enzyme activity, unlike those previously phenotyped by determining allelic transcript expression. Furthermore the one lactase persistent homozygote identified by having equally high expression of A and B haplotype transcripts, was heterozygous for CT at the ,14 kb site. SNP analysis across the 1 megabase region in this person showed no evidence of recombination on either chromosome between the ,14 kb SNP and LCT. The combined data shows that although the ,14 kb CT SNP is an excellent candidate for the cause of the lactase persistence polymorphism, linkage disequilibrium extends far beyond the region searched so far. In addition, the CT SNP does not, on its own, explain all the variation in expression of LCT, suggesting the possibility of genetic heterogeneity. [source]

    A Monetary Approach to Exchange Market Disequilibrium in Australia: 1975,97

    M. A. Taslim
    Under a managed float, the central bank may respond to an exchange market disequilibrium by changing either the international reserves or the exchange rate or both such that neither the reserve changes nor the exchange rate movements convey an unambiguous indication of the nature or extent of the disequilibrium. Girton and Roper (1977) suggested an index, namely the exchange market pressure, to capture the disequilibrium. This paper utilises a similar framework to study the exchange market pressure in Australia during 1975,1997 and reserve transactions. It is found that there were substantial reserve transactions in the face of exchange market pressure even after the switch to the floating rate system and the deregulation of the financial system. As a result of these transactions, sharp fluctuations in the exchange rate were moderated and the actual exchange rate appeared to broadly follow the market equilibrium rate. [source]

    Linkage disequilibrium and natural selection for mimicry in the Batesian mimic Hypolimnas misippus (L.) (Lepidoptera: Nymphalidae) in the Afrotropics

    On two occasions, on opposite sides of the African continent (Cape Coast, Ghana, and Dar es Salaam, Tanzania), high adult population densities in the polymorphic butterfly Hypolimnas misippus (a presumed mimic of Danaus chrysippus) were followed by linkage disequilibrium in combinations of fore- and hindwing colour patterns. On both occasions, disequilibrium was caused by significant changes in morph frequencies favouring rarer and more mimetic forms. Recaptures were too few for analysis at Dar, although the changes there took place within a single generation and must have been the result of differential survival. Recapture rate data and survival rate estimates at Cape Coast support the hypothesis that selective predation was responsible, as does the observation of synchronous linkage disequilibrium at Dar in the model D. chrysippus, indicating parasitic mimicry. There was clear selection for the perfection of mimicry for forewings at Dar and for hindwings at Cape Coast. Disequilibrium is also reported for two other sites, Legon (Ghana) and Boksburg (South Africa) and, in all four sites, it was associated with an increase in the most mimetic forms. New chemical evidence is presented to support the contention that D. chrysippus is a defended model. Although all the evidence leads to the conclusion that H. misippus is a Batesian mimic of D. chrysippus, many questions remain, particularly with regard to the identity of predators, the episodic nature of selective predation events, and their apparent lack of lasting and significant impact on overall gene frequencies. We conclude that H. misippus presents both challenges and opportunities for studies on mimicry, and we suggest that linkage disequilibrium can be a useful generic indicator for Gestalt predation on polymorphic prey. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 100, 180,194. [source]

    Polymorphisms in the interleukin-1 gene influence the stratum corneum interleukin-1, concentration in uninvolved skin of patients with chronic irritant contact dermatitis

    CONTACT DERMATITIS, Issue 5 2008
    Cindy M. DeJongh
    Background:, Interleukin (IL)-1, and its receptor antagonist IL-1ra play a role in skin inflammation. Several polymorphisms in the IL1 gene cluster, coding for IL-1,, IL-1ra, and IL-1,, influence their protein expression. Within this cluster, strong linkage disequilibrium has been shown. Objective:, We studied the association between the polymorphisms IL1A -889 (C,T) and IL1B -31 (T,C) and the concentration of IL-1, and IL-1ra in the stratum corneum (SC). Method:, In 124 patients with chronic irritant contact dermatitis, we genotyped the IL1A -889 and IL1B -31 polymorphisms and determined the amount of IL-1, and IL-1ra on tape strips obtained from uninvolved skin of the volar forearm. Results:, The SC IL-1, concentration was 23% and 47% lower in subjects with IL1A -889 C/T genotype and T/T genotype, respectively, compared with wild-type genotype. In subjects with IL1B -31 C/C genotype, the IL-1, concentration was 51% lower compared with C/T and T/T genotypes. The ratio IL-1ra/IL-1, increased twofold in IL1A -889 C/T genotype and threefold in T/T genotype compared with wild type. Conclusions:, We have shown a clear effect of IL1 genotype on protein expression in the SC. This altered expression may be responsible for the interindividual differences in the inflammatory response of the skin. [source]

    Effect of RBP4 gene variants on circulating RBP4 concentration and Type 2 diabetes in a Chinese population

    DIABETIC MEDICINE, Issue 1 2008
    C. Hu
    Abstract Aims Retinol binding protein 4 (RBP4) is a newly discovered adipokine, which plays a role in insulin resistance and obesity. The aim of this study was to determine the relationship between genetic variants of the RBP4 gene, circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism in the Chinese population. Methods We sequenced exons and the putative promoter region to identify single nucleotide polymorphisms (SNPs) in the RBP4 gene in 32 Chinese subjects. Additional SNPs were selected from a public database to increase marker density. Taking account of the pairwise linkage disequilibrium and minor allele frequencies, a subset of SNPs was further genotyped in 255 Type 2 diabetic patients and 372 normal control subjects. Circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism were measured. Results Ten SNPs were identified and five were further genotyped in the full sample. No individual SNP was significantly associated with Type 2 diabetes, but a rare haplotype CAA formed by +5388 C>T, +8201 T>A and +8204 T>A was more frequent in diabetic patients (P = 0.0343, empirical P = 0.0659 on 10 000 permutations). In both groups, non-coding SNPs were associated with circulating RBP4 concentrations (P < 0.05). In the normal control subjects, the SNP +5388 C>T was associated with serum C-peptide levels both fasting and 2 h after an oral glucose tolerance test (P = 0.0162 and P = 0.0075, respectively). Conclusion Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism. [source]

    Peroxisome proliferator-activated receptor-, co-activator-1, (PGC-1,) gene polymorphisms and their relationship to Type 2 diabetes in Asian Indians

    DIABETIC MEDICINE, Issue 11 2005
    K. S. Vimaleswaran
    Abstract Aims The objective of the present investigation was to examine the relationship of three polymorphisms, Thr394Thr, Gly482Ser and +A2962G, of the peroxisome proliferator activated receptor-, co-activator-1 alpha (PGC-1,) gene with Type 2 diabetes in Asian Indians. Methods The study group comprised 515 Type 2 diabetic and 882 normal glucose tolerant subjects chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The three polymorphisms were genotyped using polymerase chain reaction,restriction fragment length polymorphism (PCR,RFLP). Haplotype frequencies were estimated using an expectation,maximization (EM) algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results The three polymorphisms studied were not in linkage disequilibrium. With respect to the Thr394Thr polymorphism, 20% of the Type 2 diabetic patients (103/515) had the GA genotype compared with 12% of the normal glucose tolerance (NGT) subjects (108/882) (P = 0.0004). The frequency of the A allele was also higher in Type 2 diabetic subjects (0.11) compared with NGT subjects (0.07) (P = 0.002). Regression analysis revealed the odds ratio for Type 2 diabetes for the susceptible genotype (XA) to be 1.683 (95% confidence intervals: 1.264,2.241, P = 0.0004). Age adjusted glycated haemoglobin (P = 0.003), serum cholesterol (P = 0.001) and low-density lipoprotein (LDL) cholesterol (P = 0.001) levels and systolic blood pressure (P = 0.001) were higher in the NGT subjects with the XA genotype compared with GG genotype. There were no differences in genotype or allelic distribution between the Type 2 diabetic and NGT subjects with respect to the Gly482Ser and +A2962G polymorphisms. Conclusions The A allele of Thr394Thr (G , A) polymorphism of the PGC-1 gene is associated with Type 2 diabetes in Asian Indian subjects and the XA genotype confers 1.6 times higher risk for Type 2 diabetes compared with the GG genotype in this population. [source]

    Regional Monopoly and Interregional and Intraregional Competition: The Parallel Trade in Coca-Cola Between Shanghai and Hangzhou in China

    ECONOMIC GEOGRAPHY, Issue 1 2006
    Godfrey Yeung
    Abstract: This article uses a "principal-agent-subagent" analytical framework and data that were collected from field surveys in China to (1) investigate the nature and causes of the parallel trade in Coca-Cola between Shanghai and Hangzhou and (2) assess the geographic and theoretical implications for the regional monopolies that have been artificially created by Coca-Cola in China. The parallel trade in Coca-Cola is sustained by its intraregional rivalry with Pepsi-Cola in Shanghai, where Coca-Cola (China) (the principal) seeks to maximize its share of the Shanghai soft-drinks market. This goal effectively supersedes the market-division strategy of Coca-Cola (China), since the gap in wholesale prices between the Shanghai and Hangzhou markets is higher than the transaction costs of engaging in parallel trade. The exclusive distributor of Coca-Cola in the Shanghai market (the subagent) makes opportunistic use of a situation in which it does not have to bear the financial consequences of the major residual claimants (the principal and other agents) and has an incentive to enter the nondesignated Coca-Cola market of Hangzhou by crossing the geographic boundary between the two regional monopolies devised by Coca-Cola. The existence of parallel trade in Coca-Cola promotes interregional competition between the Shanghai and Hangzhou bottlers (the agents). This article enhances an understanding of the economic geography of spatial equilibrium, disequilibrium, and quasi-equilibrium of a transnational corporation's distribution system and its artificially created market boundary in China. [source]

    Austria's Demand for International Reserves and Monetary Disequilibrium: The Case of a Small Open Economy with a Fixed Exchange Rate Regime

    ECONOMICA, Issue 281 2004
    Harald Badinger
    Using a vector error correction approach, I estimate Austria's demand for international reserves over the period 1985:1,1997:4 and test for short-run effects of the disequilibrium on the national monetary market. I find that Austria's long-run reserve demand can be described as a stable function of imports, uncertainty and the opportunity cost of holding reserves with strong economies of scale. The speed of adjustment takes a value of 38 per cent. The results confirm that an excess of money demand (supply) induces an inflow (outflow) of international reserves as postulated by the monetary approach to the balance of payments. [source]

    Further evidence for an association between the gamma-aminobutyric acid receptor A, subunit 4 genes on chromosome 4 and Fagerström Test for Nicotine Dependence

    ADDICTION, Issue 3 2009
    Arpana Agrawal
    ABSTRACT Aims A previous association analysis identified polymorphisms in gamma-aminobutyric acid receptor A, subunit 4 (GABRA4) and GABRA2 to be associated with nicotine dependence, as assessed by a score of 4 or more on the Fagerström Test for Nicotine Dependence (FTND). In the present report, we extend the previous study by expanding our genotyping efforts significantly for these two genes. Design In 1049 cases (FTND of 4 or more) and 872 controls (smokers with FTND of 0) from the United States and Australia, we examine the association between 23 GABRA4 and 39 GABRA2 recently genotyped single nucleotide polymorphisms (SNPs) and nicotine dependence using logistic regression-based association analyses using the genomic analysis package PLINK. Results Two and 18 additional SNPs in GABRA4 and GABRA2, respectively, were associated with nicotine dependence. The SNPs identified in GABRA4 (P -value = 0.002) were restricted to introns 1 and 2, exon 1 and the 5, end of the gene, while those in GABRA2 localized to the 3, end of the gene and spanned introns 9,3, and were in moderate to high linkage disequilibrium (as measured by r2) with each other and with previously studied polymorphisms. Conclusion Our findings demonstrate consistently the role of GABRA4 and GABRA2 in nicotine dependence. However, further research is needed to identify the biological influence of these intronic variations and to isolate functionally relevant polymorphisms neighboring them. [source]

    The recent breakthroughs in the understanding of host genomics in hepatitis C

    Andri Rauch
    Eur J Clin Invest 2010; 40 (10): 950,959 Abstract Background, Hepatitis C Virus (HCV) infection is spontaneously resolved in about 30% of acutely infected individuals. In those who progress to chronic hepatitis C, HCV therapy permanently eradicates infection in about 40% of cases. It has long been suspected that host genetic factors are key determinants for the control of HCV infection. Design, We will review in this study four genome-wide association studies (GWAS) and two large candidate gene studies that assessed the role of host genetic variation for the natural and treatment-induced control of HCV infection. Results, The studies consistently identified genetic variation in interleukin 28B (IL28B) as the strongest predictor for the control of HCV infection. Importantly, single nucleotide polymorphisms (SNPs) in IL28B strongly predicted both spontaneous and treatment-induced HCV recovery. IL28B is located on chromosome 19 and encodes interferon-,, a type III interferon with antiviral activity, which is mediated through the JAK-STAT pathway by inducing interferon-stimulated genes. The SNPs identified in the GWAS are in high linkage disequilibrium with coding or functional non-coding SNPs that might modulate function and/or expression of IL28B. The role of the different IL28B alleles on gene expression and cytokine function has not yet been established. Conclusions, These findings provide strong genetic evidence for the influence of interferon-, for both the natural and treatment-induced control of HCV infection, and support the further investigation of interferon-, for the treatment of chronic hepatitis C. Furthermore, genetic testing before HCV therapy could provide important information towards an individualized HCV treatment. [source]

    PON1 L55M polymorphism is not a predictor of coronary atherosclerosis either alone or in combination with Q192R polymorphism in an Italian population

    M. Arca
    Abstract Background, The present study evaluated the role of the PON1 L55M polymorphism independently and in conjunction with the Q192R polymorphism on the risk of coronary atherosclerosis in an Italian population. Materials and methods, Three hundred and ninety-one subjects with significant coronary stenosis (> 50%) (coronary artery disease-positive; CAD+), 196 subjects with normal coronary arteries (< 10% stenosis) (CAD,) and 178 healthy controls were screened using a combination of polymerase chain reaction and restriction enzyme digestion. Results, In the pooled population, the frequencies of L and M alleles were 0·63 and 0·37, respectively; the most common haplotypes were QQ/LM (24·2%) and QR/LL (21·8%) and a strong linkage disequilibrium between L/55 and R/192 alleles was observed (D, = ,0·91; P < 0·0001). CAD+ subjects did not show any significant differences in the distribution of PON1,55 genotypes as compared to CAD, subjects and population controls (,2 = 1·5, P = 0·8). After controlling for other risk factors, the low-concentration M allele was not associated with a significant change of CAD risk (OR 1·02; 95% CI 0·80,1·29; P = 0·87). Moreover, the L55M polymorphism did not show any interaction with other risk factors such as smoking, diabetes, hypertension, low levels of high-density lipoprotein (HDL) or high ratios of low-density to high-density lipoproteins. The combination of L55M with the Q192R polymorphism did not show any effect on CAD risk. However, a marginal decrease in myocardial infarction risk was detected when QQ/MM carriers (OR 0·51; 95% CI 0·26,0·99; P = 0·048), but not LL/RR carriers, were compared with subjects not homozygous for an L or R allele. Conclusions, These findings did not indicate a major effect of the PON1 L55M polymorphism, either alone or in combination with the Q192R polymorphism, on CAD risk. Additional studies are needed for a better evaluation of the role of the 55/192 PON1 genotypes in combination on myocardial infarction risk. [source]

    GENETIC STUDY: H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependence

    ADDICTION BIOLOGY, Issue 1 2010
    Elliot C. Nelson
    ABSTRACT Animal research supports a central role for corticotropin-releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype × environment (G × E) interaction involving rs1876831, a corticotropin-releasing hormone receptor 1 (CRHR1) polymorphism, and negative events. CRHR1 and at least four other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype. Here, we examine whether G × E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (n = 1128 respondents from 476 families) of the Nicotine Addiction Genetics project. Telephone interviews provided data on DSM-IV alcohol dependence diagnosis and CSA and enabled calculation of lifetime alcohol consumption factor score (ACFS) from four indices of alcohol consumption. Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence. A significant G × E interaction was found for ACFS involving the H2 haplotype and CSA (P < 0.017). A similar G × E interaction was associated with protective effects against alcohol dependence risk (odds ratio 0.42; 95% confidence interval 0.20,0.89). For each outcome, no significant CSA-associated risk was observed in H2 haplotype carriers. These findings support conducting further investigation of the H2 haplotype to determine the gene(s) responsible. Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence. [source]

    GENETIC STUDY: Association between the nociceptin receptor gene (OPRL1) single nucleotide polymorphisms and alcohol dependence

    ADDICTION BIOLOGY, Issue 1 2008
    Jia Huang
    ABSTRACT OPRL1 encodes the nociceptin receptor, which has been shown to be involved in alcohol dependence in previous studies. In the present study, we investigated the association between genetic polymorphisms of OPRL1 and alcohol dependence in a Scandinavian population. We genotyped 15 single nucleotide polymorphisms (SNPs) spanning the OPRL1 locus and found that SNP rs6010718 was significantly associated with both Type I and Type II alcoholics (P < 0.05). Linkage disequilibrium and haplotype analysis identified two haplotype blocks in this region. Furthermore, two haplotypes composed of five tag SNPs showed significant association with alcohol dependence. These findings suggest that genetic variants of the OPRL1 gene play a role in alcohol dependence in the Scandinavian population, warranting further investigation at the OPRL1 locus. [source]


    EVOLUTION, Issue 12 2009
    Alan Brelsford
    Hybrid zones between recently diverged taxa are natural laboratories for speciation research, allowing us to determine whether there is reproductive isolation between divergent forms and the causes of that isolation. We present a study of a classic avian hybrid zone in North America between two subspecies of the yellow-rumped warbler (Dendroica coronata). Although previous work has shown very little differentiation in mitochondrial DNA across this hybrid zone, we identified two nuclear loci (one sex-linked and one autosomal) that show fixed differences across the hybrid zone, in a close concordance with patterns of plumage variation. Temporal stability and limited width of the hybrid zone, along with substantial linkage disequilibrium between these two diagnostic markers in the center of the zone, indicate that there is moderate reproductive isolation between these populations, with an estimated strength of selection maintaining the zone of 18%. Pairing data indicate that assortative mating is either very weak or absent, suggesting that this reproductive isolation is largely due to postmating barriers. Thus, despite extensive hybridization the two forms are distinct evolutionary groups carrying genes for divergent adaptive peaks, and this situation appears relatively stable. [source]


    EVOLUTION, Issue 1 2009
    Takeshi Kawakami
    Whether chromosomal rearrangements promote speciation by providing barriers to gene exchange between populations is one of the long-standing debates in evolutionary biology. This question can be addressed by studying patterns of gene flow and selection in hybrid zones between chromosomally diverse taxa. Here we present results of the first study of the genetic structure of a hybrid zone between chromosomal races of morabine grasshoppers Vandiemenella viatica, P24(XY) and viatica17, on Kangaroo Island, Australia. Chromosomal and 11 nuclear markers revealed a narrow hybrid zone with strong linkage disequilibrium and heterozygote deficits, most likely maintained by a balance between dispersal and selection. Widths and positions of clines for these markers are concordant and coincident, suggesting that selection is unlikely to be concentrated on a few chromosomes. In contrast, a mitochondrial marker showed a significantly wider cline with centre offset toward the P24(XY) side. We argue that the discordance between the mitochondrial and nuclear/chromosomal clines and overall asymmetry of the clines suggest a secondary origin of the contact zone and potential movement of the zone after contact. Genome-wide scans using many genetic markers and chromosomal mapping of these markers are needed to investigate whether chromosomal differences directly reduce gene flow after secondary contact. [source]


    EVOLUTION, Issue 11 2005
    John S. Heywood
    Abstract Starting with the Price equation, I show that the total evolutionary change in mean phenotype that occurs in the presence of fitness variation can be partitioned exactly into five components representing logically distinct processes. One component is the linear response to selection, as represented by the breeder's equation of quantitative genetics, but with heritability defined as the linear regression coefficient of mean offspring phenotype on parent phenotype. The other components are identified as constitutive transmission bias, two types of induced transmission bias, and a spurious response to selection caused by a covariance between parental fitness and offspring phenotype that cannot be predicted from parental phenotypes. The partitioning can be accomplished in two ways, one with heritability measured before (in the absence of) selection, and the other with heritability measured after (in the presence of) selection. Measuring heritability after selection, though unconventional, yields a representation for the linear response to selection that is most consistent with Darwinian evolution by natural selection because the response to selection is determined by the reproductive features of the selected group, not of the parent population as a whole. The analysis of an explicitly Mendelian model shows that the relative contributions of the five terms to the total evolutionary change depends on the level of organization (gene, individual, or mated pair) at which the parent population is divided into phenotypes, with each frame of reference providing unique insight. It is shown that all five components of phenotypic evolution will generally have nonzero values as a result of various combinations of the normal features of Mendelian populations, including biparental sex, allelic dominance, inbreeding, epistasis, linkage disequilibrium, and environmental covariances between traits. Additive genetic variance can be a poor predictor of the adaptive response to selection in these models. The narrow-sense heritability s,2A/s,2P should be viewed as an approximation to the offspring-parent linear regression rather than the other way around. [source]


    EVOLUTION, Issue 8 2004
    Erica Bree Rosenblum
    Abstract The wealth of information on the genetics of pigmentation and the clear fitness consequences of many pigmentation phenotypes provide an opportunity to study the molecular basis of an ecologically important trait. The melanocortin-1 receptor (Mc1r) is responsible for intraspecific color variation in mammals and birds. Here, we study the molecular evolution of Mc1r and investigate its role in adaptive intraspecific color differences in reptiles. We sequenced the complete Mc1r locus in seven phylogenetically diverse squamate species with melanic or blanched forms associated with different colored substrates or thermal environments. We found that patterns of amino acid substitution across different regions of the receptor are similar to the patterns seen in mammals, suggesting comparable levels of constraint and probably a conserved function for Mc1r in mammals and reptiles. We also found high levels of silent-site heterozygosity in all species, consistent with a high mutation rate or large long-term effective population size. Mc1r polymorphisms were strongly associated with color differences in Holbrookia maculata and Aspidoscelis inornata. In A. inornata, several observations suggest that Mc1r mutations may contribute to differences in color: (1) a strong association is observed between one Mc1r amino acid substitution and dorsal color; (2) no significant population structure was detected among individuals from these populations at the mitochondrial ND4 gene; (3) the distribution of allele frequencies at Mc1r deviates from neutral expectations; and (4) patterns of linkage disequilibrium at Mc1r are consistent with recent selection. This study provides comparative data on a nuclear gene in reptiles and highlights the utility of a candidate-gene approach for understanding the evolution of genes involved in vertebrate adaptation. [source]


    EVOLUTION, Issue 7 2004
    Ben L. Phillips
    Abstract Phylogeographic analyses of the fauna of the Australian wet tropics rainforest have provided strong evidence for long-term isolation of populations among allopatric refugia, yet typically there is no corresponding divergence in morphology. This system provides an opportunity to examine the consequences of geographic isolation, independent of morphological divergence, and thus to assess the broader significance of historical subdivisions revealed through mitochondrial DNA phylogeography. We have located and characterized a zone of secondary contact between two long isolated (mtDNA divergence > 15%) lineages of the skink Carlia rubrigularis using one mitochondrial and eight nuclear (two intron, six microsatellite) markers. This revealed a remarkably narrow (width<3 km) hybrid zone with substantial linkage disequilibrium and strong deficits of heterozygotes at two of three nuclear loci with diagnostic alleles. Cline centers were coincident across loci. Using a novel form of likelihood analysis, we were unable to distinguish between sigmoidal and stepped cline shapes except at one nuclear locus for which the latter was inferred. Given estimated dispersal rates of 90,133 m X gen,1/2 and assuming equilibrium, the observed cline widths suggest effective selection against heterozygotes of at least 22,49% and possibly as high as 70%. These observations reveal substantial postmating isolation, although the absence of consistent deviations from Hardy-Weinberg equilibrium at diagnostic loci suggests that there is little accompanying premating isolation. The tight geographic correspondence between transitions in mtDNA and those for nuclear genes and corresponding evidence for selection against hybrids indicates that these morphologically cryptic phylogroups could be considered as incipient species. Nonetheless, we caution against the use of mtDNA phylogeography as a sole criterion for defining species boundaries. [source]


    EVOLUTION, Issue 1 2002
    Abstract According to classical evolutionary theory, sexual recombination can generate the variation necessary to adapt to changing environments and thereby confer an evolutionary advantage of sexual over asexual reproduction. Using the green alga, Chlamydomonas reinhardtii, we investigated the effect of a single sexual episode on adaptation of heterotrophic growth on different carbon sources. In an initial mixture of isolates, sex was induced and the resulting offspring constituted the sexual populations, along with any unmated vegetative cells; the unmated mixture of isolates represented the asexual populations. Mean and variance in division rates (i.e., fitness) were measured four times during approximately 50 generations of vegetative growth in the dark on all possible combinations of four carbon sources. Consistent with effects of recombination of epistatic genes in linkage disequilibrium, sexual populations initially had a higher variance in fitness, but their mean fitness was lower than that of asexual populations, possibly due to recombinational load. Subsequently, fitness of sexual populations exceeded that of asexual ones, but finally they regained parity in both mean and variance of fitness. Although recombination was not more effective on more complex substrates, these results generally support the idea that sex can accelerate adaptation to novel environments. [source]


    EVOLUTION, Issue 5 2000
    Hansjürg Hotz
    Abstract The European pool frog, Rana lessonae, is widely polymorphic for two common alleles (b, e) at the lactate dehydrogenase-B (LDH-B) locus. We compared fitness-related larval life-history traits among LDH-B genotypes, which originated from segregation in heterozygous parents, in an artificial pond experiment where tadpoles of R. lessonae from a Swiss population were raised together with tadpoles of the hemiclonal hybrid R. esculenta at two densities. In R. lessonae, LDH-B e/e homozygotes at each density had a higher proportion of metamorphs among survivors, reached metamorphosis earlier, and were heavier at metamorphosis than b/b homozygotes; b/e heterozygotes had intermediate values. That e/e individuals were superior to b/b in both time to and mass at metamorphosis is surprising because these two life-history traits are thought to reflect a performance trade-off; e/e genotypes apparently compensated for shorter time to metamorphosis by a higher growth rate. The two alleles showed the same performance ranking when combined in hybrids with a R. ridibunda allele: When R. esculenta from Swiss populations reared in the same ponds had received the e allele rather than the b allele from their R. lessonae parent, they reached metamorphosis earlier, but did not differ in mass at metamorphosis. The degree of linkage disequilibrium in the source population of the eight R. lessonae used as parents of the R. lessonae tadpoles is unknown, so we cannot exclude the possibility that the performance differences are caused by some anonymous tightly linked gene, rather than the LDH-B locus, that constitutes the genomically localized target of natural selection. A causal involvement of LDH-B is plausible, nevertheless, because this enzyme takes part in the central energy-metabolizing processes and has been reported to underlie fitness differences in other animals; also, differential performance of LDH-B genotypes has been observed in R. lessonae larvae from another population. The present results suggest strong directional selection for allele e; the sum of available data, including an independent laboratory experiment, suggests that partial environment-dependent overdominance combined with balancing selection favoring e/e homozygotes under some and b/b homozygotes under other conditions may be partially responsible for the broad maintenance of the LDH-B polymorphism in R. lessonae. [source]


    EVOLUTION, Issue 1 2000
    Tadeusz J. Kawecki
    Abstract., If the direction of selection changes from generation to generation, the ability to respond to selection is maladaptive: the response to selection in one generation leads to reduced fitness in the next. Because the response is determined by the amount of genetic variance expressed at the phenotypic level, rapidly fluctuating selection should favor modifier genes that reduce the phenotypic effect of alleles segregating at structural loci underlying the trait. Such reduction in phenotypic expression of genetic variation has been named "genetic canalization." I support this argument with a series of two- and multilocus models with alternating linear selection and Gaussian selection with fluctuating optimum. A canalizing modifier gene affects the fitness of its carriers in three ways: (1) it reduces the phenotypic consequences of genetic response to previous selection; (2) it reduces the genetic response to selection, which is manifested as linkage disequilibrium between the modifier and structural loci; and (3) it reduces the phenotypic variance. The first two effects reduce fitness under directional selection sustained for several generations, but improve fitness when the direction of selection has just been reversed. The net effect tends to favor a canalizing modifier under rapidly fluctuating selection regimes (period of eight generations or less). The third effect improves fitness of the modifier allele if the fitness function is convex and reduces it if the function is concave. Under fluctuating Gaussian selection, the population is more likely to experience the concave portion of the fitness function when selection is stronger. Therefore, only weak to moderately strong fluctuating Gaussian selection favors genetic canalization. This paper considerably broadens the conditions that favor genetic canalization, which so far has only been postulated to evolve under long-term stabilizing selection. [source]

    Linkage disequilibrium estimates of contemporary Ne using highly variable genetic markers: a largely untapped resource for applied conservation and evolution

    Robin S. Waples
    Abstract Genetic methods are routinely used to estimate contemporary effective population size (Ne) in natural populations, but the vast majority of applications have used only the temporal (two-sample) method. We use simulated data to evaluate how highly polymorphic molecular markers affect precision and bias in the single-sample method based on linkage disequilibrium (LD). Results of this study are as follows: (1) Low-frequency alleles upwardly bias , but a simple rule can reduce bias to [source]

    Common polymorphisms in the interleukin-22 gene are not associated with chronic plaque psoriasis

    Wolfgang Weger
    Abstract Background:, Psoriasis is a chronic inflammatory skin disease. Among other cytokines, interleukin 22 (IL-22) has been implicated in the pathogenesis of chronic plaque psoriasis. The purpose of this study was to investigate a hypothesized association between common IL-22 gene polymorphisms and chronic plaque psoriasis. Methods:, Genotypes of 10 common polymorphisms of the IL-22 gene were determined by fluorogenic 5, exonuclease assays (TaqMan) in 475 patients with chronic plaque psoriasis and 252 controls. Results:, Two blocks of high linkage disequilibrium, formed by eight polymorphisms upstream of exon 5 (rs2227485, rs2227491, rs2046068, rs1179251, rs1012356, rs2227501, rs2227503, rs976748) and two polymorphisms in the 3, near gene region (rs1182844, rs1179246), were observed within the IL-22 gene. Neither single polymorphisms nor haplotypes were significantly associated with the presence or clinical features of chronic plaque psoriasis (P > 0.05). Conclusions:, Our data suggest that the investigated IL-22 gene polymorphisms are unlikely major risk factors for chronic plaque psoriasis. [source]

    SPR1 gene near HLA-C is unlikely to be a psoriasis susceptibility gene

    Y. T. Chang
    Abstract:, Although genetics analyses have identified the HLA-Cw6 allele to be the major risk allele for psoriasis vulgaris (PV) in many racial groups, it has been proposed that other putative genes near the HLA-C locus are involved in PV susceptibility and that the association of Cw6 is a result of linkage disequilibrium. The SPR1 gene, a predicted gene located 128 kb telomeric to the HLA-C locus, is considered to be one potential candidate gene of PV. Until now, no association study of the SPR1 gene has been conducted on psoriasis patients. We investigated the SPR1 gene for disease association by direct sequencing of the SPR1 gene in 116 Chinese patients with PV and 116 normal subjects. Genotyping for HLA-Cw6 was also carried out using polymerase chain reaction/restriction fragment length polymorphism. Significant increase of the HLA-Cw6 allele was found in psoriasis patients (32.8% vs. 13.8%, P = 0.001). We found that the SPR1 gene is a highly polymorphic gene containing 13 single nucleotide polymorphisms (SNPs), two of which have not been previously reported, and four SNPs cause amino acid change. No significantly different allelic distribution of 13 SPR1 SNPs could be found between the patients with PV and controls after correction for multiple testing. If the frequencies of SPR1 SNPs were compared between the early onset psoriatics and control subjects, early onset patients were more likely to have G allele at position 988 (60% vs. 35.3%, P = 0.001). However, the significance disappeared upon stratification for the Cw6 status. Haplotype-based association analysis showed two susceptibility haplotypes (types 8 and 19) in early onset psoriasis patients. Nonetheless, the significance also disappeared after stratification of the Cw6 status. Our results suggest that HLA-Cw6 remains the major risk allele in Chinese psoriatics, and that the SPR1 gene might not play an important role in the causation of PV. [source]