In population genetics, linkage disequilibrium is the non-random association of alleles at different loci in a given population. Loci are said to be in linkage disequilibrium when the frequency of association of their different alleles is higher or lower than what would be expected if the loci were independent and associated randomly.[1]. Linkage disequilibrium is influenced by many factors, including selection, the rate of recombination, the rate of mutation, genetic drift, the system of mating, population structure, and genetic linkage. As a result, the pattern of linkage disequilibrium in a genome is a powerful signal of the population genetic processes that are structuring it.. In spite of its name, linkage disequilibrium may exist between alleles at different loci without any genetic linkage between them and independently of whether or not allele frequencies are in equilibrium (not changing with time).[1] Furthermore, linkage disequilibrium is sometimes referred to as gametic phase ...
Effective identification of disease-causing gene locations can have significant impact on patient management decisions that will ultimately increase survival rates and improve the overall quality of health care. Linkage disequilibrium mapping is the process of finding disease gene locations through comparisons of haplotype frequencies between disease chromosomes and normal chromosomes. This work presents a new method for linkage disequilibrium mapping. The main advantage of the proposed algorithm, called LinkageTracker, is its consistency in producing good predictive accuracy under different conditions, including extreme conditions where the occurrence of disease samples with the mutation of interest is very low and there is presence of error or noise. We compared our method with some leading methods in linkage disequilibrium mapping such as HapMiner, Blade, GeneRecon, and Haplotype Pattern Mining (HPM). Experimental results show that for a substantial class of problems, our method has good predictive
Abstract: "Allelic variations in the genes involving the dopaminergic system, particularly the dopamine transporter (DAT1/SLC6A3), dopamine receptor 4 (DRD4) and Catecol-O-Methyltransferase (COMT) genes have been associated with Attention Deficit Hyperactivity Disorder (AD/HD). However, the results of these studies have been variable and inconclusive in part due to the inconsistencies of experimental and statistical methodologies, phenotypic heterogeneity, low penetrance of the genes implicated, and population stratification. Genetic association studies based on linkage disequilibrium (LD) offer a promising approach to the study of common complex diseases. This study characterized LD patterns in three human populations (CEU, YRI, CHB+JPT) in the three genes mentioned above and identified factors affecting the inconsistencies of genetic association studies in AD/HD. We used the HapMap database and the Haploview program to evaluate linkage disequilibrium patterns of SNPs in these genes. The ...
Descrição: We constructed a metric linkage disequilibrium (LD) map of bovine chromosome 6 (BTA6) on the basis of data from 220 SNPs genotyped on 433 Australian dairy bulls. This metric LD map has distances in LD units (LDUs) that are analogous to centimorgans in linkage maps. The LD map of BTA6 has a total length of 8.9 LDUs. Within the LD map, regions of high LD (represented as blocks) and regions of low LD (steps) are observed, when plotted against the integrated map in kilobases. At the most stringent block definition, namely a set of loci with zero LDU increase over the span of these markers, BTA6 comprises 40 blocks, accounting for 41% of the chromosome. At a slightly lower stringency of block definition (a set of loci covering a maximum of 0.2 LDUs on the LD map), up to 81% of BTA6 is spanned by 46 blocks and with 13 steps that are likely to reflect recombination hot spots. The mean swept radius (the distance over which LD is likely to be useful for mapping) is 13.3 Mb, confirming ...
The human Xp/Yp telomere-junction region exhibits high levels of sequence polymorphism and linkage disequilibrium. To determine whether this is a general feature of human telomeres, we have undertaken sequence analysis at the 12q telomere and have extended the analysis at Xp/Yp. A total of 22 single-nucleotide polymorphisms (SNPs) and one 30-bp duplication were detected in the 1,870 bp adjacent to the 12q telomere. Twenty polymorphic positions were in almost complete linkage disequilibrium, creating three common diverged haplotypes accounting for 80% of 12q telomeres in the white population. A further 6% of 12q telomeres contained a 1,439-bp deletion in the DNA flanking the telomere. The remaining 13% of 12q telomeres did not amplify with the primers used (nulls). The distribution of telomere (TTAGGG) and variant repeats within 12q telomeres was hypervariable, but alleles with similar distribution patterns were associated with the same haplotype in the telomere-adjacent DNA. These data suggest ...
We previously reported genome-wide significant evidence for linkage between chromosome 6q and bipolar I disorder (BPI) by performing a meta-analysis of original genotype data from 11 genome scan linkage studies. We now present follow-up linkage disequilibrium mapping of the linked region utilizing 3,047 single nucleotide polymorphism (SNP) markers in a case-control sample (N = 530 cases, 534 controls) and family-based sample (N = 256 nuclear families, 1,301 individuals). The strongest single SNP result (rs6938431, P = 6.72 x 10(-5)) was observed in the case-control sample, near the solute carrier family 22, member 16 gene (SLC22A16). In a replication study, we genotyped 151 SNPs in an independent sample (N = 622 cases, 1,181 controls) and observed further evidence of association between variants at SLC22A16 and BPI. Although consistent evidence of association with any single variant was not seen across samples, SNP-wise and gene-based test results in the three samples provided convergent evidence for
TY - JOUR. T1 - Single-nucleotide polymorphisms in the interleukin-10 gene: Differences in frequencies, linkage disequilibrium patterns, and haplotypes in three United States ethnic groups. AU - Lazarus, R. AU - Klimecki, WT. AU - Palmer, Lyle. AU - Kwiatkowski, DJ. AU - Silverman, EK. AU - Brown, A. AU - Martinez, F. AU - Weiss, ST. PY - 2002. Y1 - 2002. N2 - Interleukin-10 (IL-10) is a cytokine that seems to function as a downregulator of the innate (nonadaptive) immune system. Approximately three-quarters of interindividual variability in human IL-10 levels has been attributed to genetic variation, and there is evidence suggesting a potential role for IL-10 in a range of human diseases. To provide a basis for haplotype analysis and future disease association studies, we characterized genetic variation in IL10 by sequencing all exons, and 2.5 kb of the 5- and the 3-flanking region in a panel of DNA samples from 24 African Americans, 23 European Americans, and 24 Hispanic Americans. The ...
BACKGROUND:Cholesterol 7-alpha-hydroxylase (CYP7A1) is the rate limiting enzyme for converting cholesterol into bile acids. Genetic variations in the CYP7A1 gene have been associated with metabolic disorders of cholesterol and bile acids, including hypercholesterolemia, hypertriglyceridemia, arteriosclerosis, and gallstone disease. Current genetic studies are focused mainly on analysis of a single nucleotide polymorphism (SNP) at A-278C in the promoter region of the CYP7A1 gene. Here we report a genetic approach for an extensive analysis on linkage disequilibrium (LD) blocks and haplotype structures of the entire CYP7A1 gene and its surrounding sequences in Africans, Caucasians, Asians, Mexican-Americans, and African-Americans.RESULT:The LD patterns and haplotype blocks of CYP7A1 gene were defined in Africans, Caucasians, and Asians using genotyping data downloaded from the HapMap database to select a set of haplotype-tagging SNPs (htSNP). A low cost, microarray-based platform on thin-film ...
Four intragenic polymorphic microsatellite markers, AAAT Alu repeat, IVS27AC28.4, ACI27.2, and IVS38GT53.0, located along a 65 kb DNA region of the NF1 gene, were used to genotype 64 Spanish families with neurofibromatosis type 1 (NF1). Linkage disequilirium between each pair of markers was evaluated. Three of these markers, AAAT Alu repeat, ACI27.2, and IVS38GT53.0, exhibit linkage disequilibrium between each other. Analysis of extended haplotypes provides further evidence of the disequilibrium within this region since only 11 haplotypes account for 52% of the total chromosomes. Because of linkage disequilibrium, the informativeness of marker combinations for genotyping of NF1 families is diminished. There was no difference in the overall distribution of alleles between affected and normal chromosomes. An at risk haplotype was not found, as expected for a disease with at least 50% of cases being sporadic.. ...
Author(s): Smit-McBride, Z; Moya, A; Ayala, FJ | Abstract: We have studied linkage disequilibrium in Drosophila melanogaster in two samples from a wild population and in four large laboratory populations derived from the wild samples. We have assayed four polymorphic enzyme loci, fairly closely linked in the third chromosome: Sod Est-6, Pgm, and Odh. The assay method used allows us to identify the allele associations separately in each of the two homologous chromosomes from each male sampled. We have detected significant linkage disequilibrium between two loci in 16.7% of the cases in the wild samples and in 27.8% of the cases in the experimental populations, considerably more than would be expected by chance alone. We have also found three-locus disequilibria in more instances than would be expected by chance. Some disequilibria present in the wild samples disappear in the experimental populations derived from them, but new ones appear over the generations. The effective population sizes required to
THE advent of dense maps of single-nucleotide polymorphisms (SNPs) covering the genome with 300,000 or more markers offers new opportunities to find and identify genes, by testing for population-level associations between the SNP and disease or other trait of interest. Associations occur because of linkage disequilibrium between the marker and trait. "Linkage disequilibrium (LD) mapping" aims to detect and locate genes relative to a map of existing genetic markers. Location information is obtained because the distance between the gene and a marker on a chromosome is one factor influencing the closeness of association between the gene and marker. In a population, recombinations affecting the association between a gene and marker may occur over many generations. This potentially gives a much finer resolution than pedigrees used for quantitative trait loci (QTL) mapping. Finer resolution comes at a cost, however. More genotyping is needed per individual and as we shall show, larger sample sizes are ...
The Transmission Disequilibrium Test (TDT) compares frequencies of transmission of two alleles from heterozygote parents to an affected offspring. This test requires all genotypes to be known from all members of the nuclear families. However, obtaining all genotypes in a study might not be possible for some families, in which case, a data set results in missing genotypes. There are many techniques of handling missing genotypes in parents but only a few in offspring. The robust TDT (rTDT) is one of the methods that handles missing genotypes for all members of nuclear families [with one affected offspring]. Even though all family members can be imputed, the rTDT is a conservative test with low power. We propose a new method, Mendelian Inheritance TDT (MITDT-ONE), that controls type I error and has high power. The MITDT-ONE uses Mendelian Inheritance properties, and takes population frequencies of the disease allele and marker allele into account in the rTDT method. One of the advantages of using the MITDT
The transmission disequilibrium test (TDT) was proposed by Spielman, McGinnis and Ewens (1993) as a family-based association test for the presence of genetic linkage between a genetic marker and a trait. It is an application of McNemars test. A specificity of the TDT is that it will detect genetic linkage only in the presence of genetic association. While genetic association can be caused by population structure, genetic linkage will not be affected, which makes the TDT robust to the presence of population structure. We first describe the TDT in the case where families consist of trios (two parents and one affected child). Our description follows the notations used in Spielman, McGinnis & Ewens (1993). The TDT measures the over-transmission of an allele from heterozygous parents to affected offsprings. The n affected offsprings have 2n parents. These can be represented by the transmitted and the non-transmitted alleles M 1 {\displaystyle M_{1}} and M 2 {\displaystyle M_{2}} at some genetic ...
The transmission disequilibrium test TDT is a useful method to locate mutations linked to disease genes associated with complex diseases. TDT requires genotypes of affected individuals and their parents. Recently, Ewens and Spielman Am J Hum Genet 1998 ; 62 : 450-8 extended the TDT for use in sibships with at least one affected and one...
Association studies based on linkage disequilibrium (LD) can provide high resolution for identifying genes that may contribute to phenotypic variation. We report patterns of local and genome-wide LD in 102 maize inbred lines representing much of the worldwide genetic diversity used in maize breeding, and address its implications for association studies in maize. In a survey of six genes, we found that intragenic LD generally declined rapidly with distance (r(2) | 0.1 within 1500 bp), but rates of decline were highly variable among genes. This rapid decline probably reflects large effective population sizes in maize during its evolution and high levels of recombination within genes. A set of 47 simple sequence repeat (SSR) loci showed stronger evidence of genome-wide LD than did single-nucleotide polymorphisms (SNPs) in candidate genes. LD was greatly reduced but not eliminated by grouping lines into three empirically determined subpopulations. SSR data also supplied evidence that divergent artificial
To investigate the relationship between meiotic crossover hot spots and block-like linkage disequilibrium (LD), we have extended our high-resolution studies of the human MHC class II region to a 90-kb segment upstream of the HLA-DOA gene. LD blocks in this region are not as well defined as in the neighboring 210-kb DNA segment but do show two regions of LD breakdown in which coalescent analysis indicates substantial historical recombination. Sperm crossover analysis of one region revealed a novel localized hot spot similar in intensity and morphology to most other MHC hot spots. Crossovers at this hot spot are not obviously affected by a large insertion/deletion polymorphism near the hot spot. The second region of LD breakdown, within the DPB1 gene, shows an extremely low level of sperm crossover activity and does not contain a sperm crossover hot spot. These results highlight the complexity of LD patterns and the importance of experimentally verifying crossover hot spots ...
The chemokine gene cluster [CCL22, CX3CL1, CCL17] (previously known as [SCYA22, SCYD1, SCYA17]) is a candidate locus for one of the susceptibility genes for inflammatory bowel disease that are located in the peri-centromeric region of chromosome 16. Screening for sequence variation at this locus led to the detection of 14 single nucleotide polymorphisms (SNPs). An efficient experimental and computational approach was developed to estimate allele frequencies and pairwise linkage disequilibrium relationships between SNPs at this locus, and to test them for association with inflammatory bowel disease. The 12 common SNPs were assigned to 5 distinct linkage disequilibrium groups. Genotyping of one SNP from each linkage disequilibrium group in a large cohort of families with inflammatory bowel disease did not provide convincing evidence of association with either Crohns disease or ulcerative colitis. We describe an efficient experimental design from SNP screening to association testing. This ...
Understanding of genetic diversity and linkage disequilibrium (LD) decay in diverse maize germplasm is fundamentally important for maize improvement. A total of 287 tropical and 160 temperate inbred lines were genotyped with 1943 single nucleotide polymorphism (SNP) markers of high quality and compared for genetic diversity and LD decay using the SNPs and their haplotypes developed from genic and intergenic regions. Intronic SNPs revealed a substantial higher variation than exonic SNPs. The big window size haplotypes (3-SNP slide-window covering 2160 kb on average) revealed much higher genetic diversity than the 10 kb-window and gene-window haplotypes. The polymorphic information content values revealed by the haplotypes (0.436-0.566) were generally much higher than individual SNPs (0.247-0.259). Cluster analysis classified the 447 maize lines into two major groups, corresponding to temperate and tropical types. The level of genetic diversity and subpopulation structure were associated with the
Hello! My name is Franco and I have been involved in the field of epidemiology and molecular biology for few months. The purpose of my research group is to perform a case-control study on a multifactorial disease, such as myocardial infarction, on the basis of different genotypes among an Italian population. Differences, or polymorphism, at different genetic loci (such as at all known risk factors for myocardial infarction genetic sites) is one of the topics of my group. Anyway, I have some unsolved questions and I would appreciate very much if someone helped me suggesting appropriate literature (sendind correctly references) or directly answering me by e-mail. Which are the mathematical basis of the linkage disequilibrium? Which are the parameters considered in the analysis? I dont understand, in a correct and simple way, the methods to analyze DNA changes on the basis of polymorphic sites (already linked, previously, to the disease!) more or less in linkage disequilibrium. Why the ...
The Saami from Fennoscandia are believed to represent an ancient, genetically isolated population with no evidence of population expansion. Theoretical work has indicated that under this demographic scenario, extensive linkage disequilibrium (LD) is generated by genetic drift. Therefore, it has been suggested that the Saami would be particularly suited for genetic association studies, offering a substantial power advantage and allowing more economic study designs. However, no study has yet assessed this claim. As part of a GWAS for a complex trait, we evaluated the relative power for association studies of common variants in the Finnish Saami. LD patterns in the Saami were very similar to those in the non-African HapMap reference panels. Haplotype diversity was reduced and, on average, levels of LD were higher in the Saami as compared with those in the HapMap panels. However, using a hidden SNP approach we show that this does not translate into a power gain in association studies. Contrary to ...
LDlink is a suite of web-based applications designed to easily and efficiently interrogate linkage disequilibrium in population groups.
We found the strongest evidence of association with a SNP in CDKN2BAS, also known as ANRIL. Previous studies reported an association of IA,2-6,18,19 as well as myocardial infarction,18 largevessel ischemic stroke subtype,20 and aortic aneurysm,18,21 with SNP in this region. Others6 examined the association in multiplex families as well as sporadic IA and found consistent evidence of association with rs1333040 (allele T), located in intron 12 of CDKN2BAS and having limited linkage disequilibrium spanning introns 7 through 15 of CDKN2BAS. The association of this SNP with both sporadic and familial IA parallels our findings. In DS1, we found evidence for association with the highrisk T allele (P=0.02; odds ratio, 1.26). We imputed this SNP in the ARIC sample and saw even greater evidence of this association in DS2 (P=1.4 × 10−5; odds ratio, 1.29). When the 2 samples were combined, the association strengthened (P=7.6 × 10−6; odds ratio, 1.29).. The linkage disequilibrium structure of the ...
Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility.
In population genetics, an ancestry-informative marker (AIM) is a single-nucleotide polymorphism that exhibits substantially different frequencies between populations from different geographical regions. A set of many AIMs can be used to estimate the proportion of ancestry of an individual derived from each geographical region. As one example, the Duffy Null allele (FY*0) has a frequency of almost 100% of Sub-Saharan Africans, but occurs very infrequently in populations outside of this region. A person having this allele is thus more likely to have Sub-Saharan African ancestors. Examining a suite of these markers more or less evenly spaced across the genome is also a cost-effective way to discover novel genes underlying complex diseases in a technique called admixture mapping or mapping by admixture linkage disequilibrium. There are an estimated 15 million SNP (Single-nucleotide polymorphism) sites (out of roughly 3 billion base pairs, or about 0.4%) from among which AIMs may potentially be ...
The gametic disequilibria between all possible pairs of loci were examined for a set of eight codominant loci in each of fifty Yanomama villages, using a multivariate correlation analysis which reduces the results to a single measure of departure from multiple-locus-gametic equilibrium. Thirty-two of the fifty villages departed significantly from multiple-locus gametic equilibrium. The largest contributions to the departure from multiple-locus equilibrium were due to the disequilibria between MN and Ss and between Rh(Cc) and Rh(Ee), indicating the effects of tight linkage. After removing the effects of these obvious sources of disequilibrium, sixteen of the fifty villages still remained significantly out of equilibrium. The disequilibrium between any particular pair of loci was highly erratic from village to village, and (with the exception of the MN-Ss and Cc-Ee disequilibria) averaged out very close to zero overall, suggesting a lack of systematic forces (epistatic selection). The departure ...
Background: MCP-1 (CCL2), MCP-3 (CCL7), and eotaxin (CCL11) are genes for CC chemokines clustered on the long arm of chromosome 17. Previous studies have implicated these chemokines in monocyte recruitment, viral replication, and anti-HIV cytotoxic T cell responses. An epidemiological analysis identified genetic variants influencing HIV-1 transmission and disease progression. Methods: Genomic DNA from over 3000 participants enrolled in five natural history cohorts in the United States were analyzed. Nine single nucleotide polymorphisms (SNP) covering 33 kb containing these three genes were genotyped using the polymerase chain reaction. Distortions in allele, genotype, and haplotype frequencies were assessed with respect to HIV-1 transmission and rates of disease progression using categorical and survival analyses. Results: Extensive linkage disequilibrium was observed. Three SNP (−2136T located in theMCP-1 promoter region, 767G in intron 1 of MCP-1, and −1385A in the Eotaxin promoter) were nearly
Citation: Perez OBrien, A.M., Meszaros, G., Utsunomiya, Y.T., Sonstegard, T.S., Fernando Garcia, J., Van Tassell, C.P., Carvalheiro, R., Da Silva, M.V., Solkner, J. 2014. Linkage disequilibrium levels in Bos indicus and Bos taurus cattle using medium and high density SNP chip data and different minor allele frequency distributions. Livestock Science. 166:121-132. Interpretive Summary: Technical Abstract: Linkage disequilibrium (LD), the observed correlation between alleles at different loci in the genome, is a determinant parameter in many applications of molecular genetics. With the wider use of genomic technologies in animal breeding and animal genetics, it is worthwhile revising and improving the current knowledge and understanding of cattle LD. This study analyzes levels of LD assessed through the r² measurement in seven breeds of cattle from both indicine (Bos indicus) and taurine (Bos taurus) (sub)species, genotyped with a high density panel (HD) of over 777000 single nucleotide ...
TY - JOUR. T1 - Comparison of the QTDT analysis for IgE in the CSGA data set. AU - Page, G. P.. AU - Wilcox, M. A.. AU - Occhiuto, J.. AU - Adak, S.. AU - Neuberg, D.. AU - Bajorunaite, R.. AU - George, V.. PY - 2001. Y1 - 2001. N2 - Over the past few years at least 13 transmission/disequilibrium test (TDT)-based tests have been developed for quantitative (Q) traits for the assessment of association or linkage in the presence of the other. A total of six of these QTDT methods were used to analyze log10IgE in the Collaborative Study on the Genetics of Asthma data set. Only moderate agreement was found between the tests. The results of the QTDT analyses were only slightly affected by the use of gender and age as covariates. Results from analysis of IgE and log10IgE were inconsistent. Our conclusion is that there is only modest agreement among the QTDT methods examined, covariates should be used even if they have a small effect, and that data should be normalized before analysis.. AB - Over the ...
In the Common QTL scenario with high historical LD, the LD model had higher accuracy than either the CS or LD-CS model (Fig. 3). For all three pedigrees, the LD-CS model had slightly lower accuracy than the LD model, but the CS model had much lower accuracy than the LD model. Accuracies from the LD and LD-CS models only decreased marginally across the eight validation generations, but the accuracy of the CS model decreased rapidly (Fig. 3). These results suggest that when historical LD between QTL and SNPs is high, the LD model has persistently high accuracy across validation generations without retraining by accurately capturing QTL effects. The CS model estimates only the values of founder alleles, and the values of recombinant alleles that are generated across generations cannot be accurately estimated. Accuracies of the LD and LD-CS models were similar for all three pedigrees, because accuracy was mostly contributed by LD that was generated historically, which was not eroded within a limited ...
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When you click on a variation ID (for example, rs1333049) from Ensembl views, the variation tab will open up (Figure 31). Figure 31. Information about rs1333049 is accessible through links in the left-hand menu, and through icons. Click on any link or icon to go to information such as population genetics, linkage disequilibrium, or phenotypes and diseases associated with this SNP. Click on the icons to find information about this SNP. Specifically: Genomic context. View the variant graphically on the genome Genes and regulation. Find out what genes might be affected by this variant Population genetics. See allele frequencies across populations Individual genotypes. Find out which alleles are carried by individuals Linkage disequilibrium. View LD plots and export values Phenotype data. See diseases and phenotypes associated with the variant Phylogenetic context. Compare the nucleotide across species Flanking sequence. View the sequence upstream and downstream of the variant Figure 32. The top panel
Abstract: In this study, five proposed causal SNPs in SERPINE2 were genotyped in 327 COPD patients and 349 controls, all of which belonged to the Han population sampled from Southwest China. The frequency of each SNP was compared both individually and in combination between patients and controls. The potential relationship between these SNPs and severity of COPD was also investigated.Three SNPs (rs3795877, rs6747096, and rs3795879) showed complete linkage disequilibrium (r2 = 1), and the minor allele frequencies were 13.0% and 12.9% in case and control cohorts, respectively, with no significant difference observed (P = 0.96). We also failed to observe any significant correlation between these SNPs and COPD severity (P = 0.67). The other two SNPs (rs7579646 and rs840088) also presented a similar pattern. Moreover, four major haplotypes were observed in our sample but none showed a significant difference between case and control groups (P > 0.1).Our results failed to obtain the evidence that these ...
Association mapping based on linkage disequilibrium (LD) is widely used to identify genomic regions containing disease variants. However, due to the complicated genetic dependence structure, identifying the underlying risk variants for complex diseases is challenging. By modeling the evolutionary process that produces our sequencing data, coalescent-based approaches may extract more information to improve such mapping. Such methods provide the genealogy at all sites in the region we have sequenced. Therefore, we can model the probability of carrying risk variants at all loci jointly, and obtain Bayesian confidence intervals (CIs) where true risk variants are most likely to occur. Additionally, the genealogy at each position provides more information about the shared ancestry of neighboring sites. Indeed, such careful modeling of the shared ancestry of sequences may also be beneficial in haplotyping and variant calling in regions of interests (ROI) where traditional hidden Markov approaches ...
Seven exons (exon B and 1-6) and ∼12 kb of the PPARγ2-specific promoter were sequenced in 24 Pima Indians. Nine SNPs were identified (Fig. 1). Two of the SNPs were in the coding region, a C/G in exon B predicting a Pro12Ala substitution (SNP8) and a C/T in exon 6 predicting a silent His477His substitution (SNP9). The other seven SNPs were in the promoter. Based on the genotypes of the 24 Pima Indians, SNP 1 appeared to be in complete linkage disequilibrium with SNP 2. SNP 6 was a common variant (allele frequency 0.58) and was positioned within a putative δEF1 binding site relatively close to the transcriptional start site of the PPARγ2 gene. Therefore, SNP 6 (C-2821T) and SNP 8, the well-documented Pro12Ala variant, were selected for our initial detailed analysis.. The C-2821T and the Pro12Ala variants were further genotyped in DNA from 985 full-blooded Pima Indians for association analyses. Both SNPs were in Hardy-Weinberg equilibrium. In addition, both SNPs were modestly associated with ...
There are several situations in population biology research where simulating DNA sequences is useful. Simulation of biological populations under different evolutionary genetic models can be undertaken using backward or forward strategies. Backward simulations, also called coalescent-based simulations, are computationally efficient. The reason is that they are based on the history of lineages with surviving offspring in the current population. On the contrary, forward simulations are less efficient because the entire population is simulated from past to present. However, the coalescent framework imposes some limitations that forward simulation does not. Hence, there is an increasing interest in forward population genetic simulation and efficient new tools have been developed recently. Software tools that allow efficient simulation of large DNA fragments under complex evolutionary models will be very helpful when trying to better understand the trace left on the DNA by the different interacting
These nuances of genetic architecture are not irrelevant to the possible evolutionary arc of the traits in question. One model of the adaptation leading to the high frequency of a trait or disease is that a novel mutation rapidly "sweeps" to fixation, or nearly to fixation. In other words, it shifts from nearly ~0% to nearly ~100% frequency in the population of alleles at that locus, driven by positive selection. This sort of rapid "hard sweep" would also result in "hitchhiking" of associated variants in the genomic regions adjacent to the originally favored mutant, producing regions of high linkage disequilibrium in the genome and haplotype blocks of associated alleles across loci. Such a model does seem possible in the case of some of the variants which are responsible for diversity of pigmentation. But this neat dovetailing between the strong association of a few variants with trait variance, and signatures of positive selection being driven by adaptation, is not so easy to come by in many ...
Pairwise linkage disequilibrium, haplotype blocks and recombination hot spots provide only a partial description of the patterns of dependences and independences between the allelic states at proximal loci. On the gross scale, where recombination and spatial relationships dominate, the associations can be reasonably described in these terms. However, on the fine scale of current high density maps the mutation process is also important and creates associations between loci which are independent of the physical ordering and which can not be summarized with pairwise measures of association. Graphical modeling provides a standard statistical framework for characterizing precisely this sort of complex stochastic data. While graphical models are often used in situations where assumptions lead naturally to specific models, it is less well known that estimation of graphical models is also a developed field. We show how decomposable graphical models can be fitted to dense genetic data. The objective ...
ATRIUM is a C++ program that performs case-control association testing between a binary trait and an untyped SNP, based on genotype data from multiple typed SNPs that are in linkage disequilibrium with the untyped SNP, where information on the joint distribution of typed and untyped SNPs is obtained from an external reference panel. A special feature of ATRIUM is that both related and unrelated individuals can be included in the case-control sample. The user specifies a set of untyped SNPs on which external reference panel information is available, and the ATRIUM program computes a test statistic for association with each untyped SNP in the set. This test is suitable for case-control analysis in any outbred sample with related and/or unrelated individuals, including large pedigrees, provided that the relationships are known ...
Linkage disequilibrium (LD) information is calculated using the 1000 Genomes Phase 3 (1KG) haplotype panel as a reference. LD is calculated in the 1KG super-population that most closely matches GWAS study ancestry information curated by the GWAS Catalog. If the study is conducted in a mixture of populations, a weighted-average (of Fisher Z-transformed correlation coefficients) across super-populations is used. If ancestry information is unknown, European ancestry is assumed. See here for full methods. ...
SNP heritability, the proportion of phenotypic variance explained by SNPs, has been estimated for many hundreds of traits, and these estimates are being used to explore genetic architecture and guide future research. To estimate SNP heritability requires strong assumptions about how heritability is distributed across the genome, but the assumptions in current use have not been thoroughly tested. By analyzing imputed data for 42 human traits, we empirically derive an improved model for heritability estimation. It is commonly assumed that the expected heritability of a SNP does not depend on its allele frequency; we instead identify a more realistic relationship which reflects that heritability tends to decrease with minor allele frequency. Two methods for estimating SNP heritability, GCTA and LDAK, make contrasting assumptions about how heritability varies with linkage disequilibrium; we demonstrate that the model used by LDAK better reflects the properties of real data. Additionally, we show how ...
Functions are provided that facilitate the import and analysis of snp and silicodart (presence/absence) data. The main focus is on data generated by DarT (Diversity Arrays Technology). However, once SNP or related fragment presence/absence data from any source is imported into a genlight object many of the functions can be used. Functions are available for input and output of SNP and silicodart data, for reporting on and filtering on various criteria (e.g. CallRate, Heterozygosity, Reproducibility, maximum allele frequency). Advanced filtering is based on Linkage Disequilibrium and HWE. Other functions are available for visualization after PCoA, or to facilitate transfer of data between genlight/genind objects and newhybrids, related, phylip packages etc.. ...
A gene variant that increases disease risk will be overrepresented among diseased persons, even compared with their own biologic parents. This insight has led to tests based solely on the asymmetric distribution of a variant allele among cases and their parents e.g., the transmission/disequilibrium test. Existing methods focus on effects of...
SNP heritability, the proportion of phenotypic variance explained by SNPs, has been estimated for many hundreds of traits, and these estimates are being used to explore genetic architecture and guide future research. To estimate SNP heritability requires strong assumptions about how heritability is distributed across the genome, but the assumptions in current use have not been thoroughly tested. By analyzing imputed data for 42 human traits, we empirically derive an improved model for heritability estimation. It is commonly assumed that the expected heritability of a SNP does not depend on its allele frequency; we instead identify a more realistic relationship which reflects that heritability tends to decrease with minor allele frequency. Two methods for estimating SNP heritability, GCTA and LDAK, make contrasting assumptions about how heritability varies with linkage disequilibrium; we demonstrate that the model used by LDAK better reflects the properties of real data. Additionally, we show how ...
SNP heritability, the proportion of phenotypic variance explained by SNPs, has been estimated for many hundreds of traits, and these estimates are being used to explore genetic architecture and guide future research. To estimate SNP heritability requires strong assumptions about how heritability is distributed across the genome, but the assumptions in current use have not been thoroughly tested. By analyzing imputed data for 42 human traits, we empirically derive an improved model for heritability estimation. It is commonly assumed that the expected heritability of a SNP does not depend on its allele frequency; we instead identify a more realistic relationship which reflects that heritability tends to decrease with minor allele frequency. Two methods for estimating SNP heritability, GCTA and LDAK, make contrasting assumptions about how heritability varies with linkage disequilibrium; we demonstrate that the model used by LDAK better reflects the properties of real data. Additionally, we show how ...
This course will cover quantitative genetic analysis of complex trait genetics with emphasis on the use of molecular markers spanning the entire genome. We will discuss statistical methodologies for connecting phenotypes with high-dimensional genomic information to better understand polygenic traits from both prediction and inference perspectives. Topics will include genomic relatedness, linkage disequilibrium, population stratification, genomic heritability, genome-enabled prediction of complex traits, and statistical learning. We will use examples from the animal, plant, and human genetics literature. Additional topics will be briefly touched upon, including sequence data, gene expression, epigenetics, and bioinformatics. Homework assignments involve hands-on analysis of simulated and real genomic data available at public repositories. The course will use R/Bioconductor software for statistical computing tools ...
Allele, Allele Frequency, Anova, Antigen, Association, Disease, Gene, Genetic Models, Haplotypes, Linkage Disequilibrium, Nucleotides, Phylogeny, Power, Recurrence, Snps, Thrombin, Tree
GENEPOP is genetics software package that does the following types of analyses: Hardy Weinberg Exact Tests Linkage Disequilibrium Population Differentiation Nm estimates Basic Information, Fis and gene diversities Fst & other correlations File Conversion Additional Miscellaneous Utilities Problems addressed by this GENEPOP workflow This specific GENEPOP workflow computes the following: Testing : Hardy-W ...
International yield trials are assembled by CIMMYT to disseminate promising wheat breeding materials worldwide. To assess the genomic structure and linkage disequilibrium (LD) within this germplasm, w
Smr74-Zz #5 Ld found in: Econo Power ABEC 5 Fishing Reel Bearing Multi Packs, SMR74-ZZC #5 LD, Boca Bearings, …any grease or oil. BocaÆs..
TY - JOUR. T1 - Epistatic control of human obesity as revealed by linkage disequilibrium mapping. T2 - A report from the NHLBI-sponsored WISE study. AU - Li, Hongying. AU - Wu, Rongling. AU - Lin, Min. AU - Terra, Steve G.. AU - Pepine, Carl J.. AU - McGorray, Susan P.. AU - Johnson, B. Delia. AU - Johnson, Julie A.. PY - 2006/11/1. Y1 - 2006/11/1. N2 - Obesity is a major risk factor for type II diabetes, hypertension, cardiovascular disease and certain forms of cancers. Obesity is a complex, multifactorial disorder, influenced by a network of genes, as well as diet, age, ethnicity, gender and exercise. Single nucleotide polymorphisms (SNPs) genotyped in six candidate genes for lipolysis and thermogenesis in human adipose tissue were used to identify and estimate epistatic quantitative trait loci (QTL) predisposing to human obesity based on linkage disequilibrium analysis for 105 black women and 538 white women drawn from the Womens Ischemia Syndrome Evaluation (WISE) study. A few pairs of ...