scholarly journals Linkage disequilibrium and haplotype block structure in Portuguese Holstein cattle

2018 ◽  
Vol 63 (No. 2) ◽  
pp. 61-69 ◽  
Author(s):  
M.M.I. Salem ◽  
G. Thompson ◽  
S. Chen ◽  
A. Beja-Pereira ◽  
J. Carvalheira
Keyword(s):  
Linkage Disequilibrium ◽  
Haplotype Block ◽  
Association Studies ◽  
Physical Distance ◽  
Allelic Association ◽  
Holstein Cattle ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Production Traits ◽  
Haplotype Blocks

The objectives of this study were to estimate linkage disequilibrium (LD), describe and scan a haplotype block for the presence of genes that may affect milk production traits in Portuguese Holstein cattle. Totally 526 animals were genotyped using the Illumina BovineSNP50 BeadChip, which contained a total of 52 890 single nucleotide polymorphisms (SNPs). The final set of markers remaining after considering quality control standards consisted of 37 031 SNPs located on 29 autosomes. The LD parameters historical recombinations through allelic association (D') and squared correlation coefficient between locus alleles frequencies ( r<sup>2</sup>) were estimated and haplotype block analyses were performed using the Haploview software. The averages of D' and r<sup>2</sup> values were 0.628 and 0.122, respectively. The LD value decreased with increasing physical distance. The D' and r<sup>2</sup> values decreased respectively from 0.815 and 0.283 at the distance of 0–30 kb to 0.578 and 0.090 at the distance of 401–500 kb. The identified total number of blocks was 969 and consisted of 4259 SNPs that covered 159.06 Mb (6.24% of the total genome) on 29 autosomes. Several genes inside the haplotype blocks were detected; CSN1S2 gene in haplotype block 51 on BTA 6, IL6 and B4GALT1 genes in haplotype blocks 6 and 33 on BTA 8, IL1B and ID2 genes in haplotype blocks 19 and 29 on BTA 11, and DGAT1 gene in haplotype block 1 on BTA 14. The extension of LD using BovineSNP50 BeadChip did not exceed 500 kb and its parameters r<sup>2</sup> and D’ were less than 0.2 and 0.70, respectively, after 70–100 kb. Consequently, the 50K BeadChip would have a poor power in genome wide association studies at distances between adjacent markers lower than 70 kb.

scholarly journals Linkage disequilibrium and haplotype block patterns in popcorn populations

2019 ◽  
Author(s):  
Andréa Carla Bastos Andrade ◽  
José Marcelo Soriano Viana ◽  
Helcio Duarte Pereira ◽  
Vitor Batista Pinto ◽  
Fabyano Fonseca e Silva
Keyword(s):  
Linkage Disequilibrium ◽  
Genomic Selection ◽  
Association Studies ◽  
Breeding Population ◽  
Human Populations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Haplotype Blocks ◽  
Genome Wide ◽  
Evolutionary Aspects

AbstractLinkage disequilibrium (LD) analysis provides information on evolutionary aspects of the populations and allows selecting populations and single nucleotide polymorphisms (SNPs) for association studies. Recently, haplotype blocks have been used to increase the power of quantitative trait loci detection in genome-wide association studies and the prediction accuracy with genomic selection. The objectives of this study were to compare the degree of LD, the LD decay, the LD decay extent, and the number and length of haplotype blocks in the populations and to elaborate the first LD map for maize, for elucidating if the maize chromosomes also had a pattern of interspaced regions of high and low rates of recombination. We used a biparental temperate population, a tropical synthetic, and a tropical breeding population, genotyped for approximately 75,000 SNPs. The level of LD expressed by the r2 values is surprisingly low (0.02, 0.04, and 0.04), but comparable to some non-isolated human populations. The general evidence is that the synthetic is the population with higher LD. It is not expected a significant advantage of haplotype-based association study and along generations genomic selection due to the reduced number of SNPs in the haplotype blocks (2 to 3). The results concerning LD decay (rapid decay after 5-10 kb) and LD decay extent (along up to 300 kb) are in the range observed with maize inbred line panels. Our most important result is that maize chromosomes had a pattern of regions of extensive LD interspaced with regions of low LD. However, our simple simulated LD map provides evidence that this pattern can reflect regions with differences of allele frequencies and LD level (expressed by D’) and not regions with high and low rates of recombination.

The effect of linkage disequilibrium on the estimates of Single Nucleotide Polymorphic effects

2009 ◽  
Vol 2009 ◽  
pp. 44-44
Author(s):  
K Moore ◽  
J Gibson ◽  
D Johnston
Keyword(s):  
Linkage Disequilibrium ◽  
Single Nucleotide Polymorphisms ◽  
Genetic Improvement ◽  
Dairy Herd ◽  
Physical Distance ◽  
Causative Mutation ◽  
Nucleotide Polymorphisms ◽  
Production Traits ◽  
Single Nucleotide Polymorphic ◽  
Single Nucleotide

The identification and exploitation of single nucleotide polymorphisms (SNP) associated with production traits present new opportunities for livestock genetic improvement. Often the identified SNP is not the causative mutation but rather is in some degree of linkage disequilibrium (LD). LD markers within 5cM can be considered as direct markers for the causative mutation because they are located close to the causative mutation (Dekkers, 2004). In a dairy herd, Farnir et al., (2000) estimated that the average LD, measured as D′ was 0.5 for loci pairs positioned within 5cM. Goddard et al., (2006) estimated that LD measured as r2 decreased rapidly as the physical distance between loci increased; at a separating distance of 0.5Mb the LD (r2) was only approximately 0.2. The aim of this work was to use stochastic simulation to investigate the effect that the distance between the SNP and causative mutation had on the accuracy of estimating additive and dominance effects of the causative mutation.

scholarly journals Confirmed effects of candidate variants for milk production, udder health, and udder morphology in dairy cattle

2020 ◽  
Vol 52 (1) ◽  
Author(s):  
Thierry Tribout ◽  
Pascal Croiseau ◽  
Rachel Lefebvre ◽  
Anne Barbat ◽  
Mekki Boussaha ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Candidate Genes ◽  
Milk Production ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Production Traits ◽  
Milk Production Traits ◽  
Udder Health ◽  
Gwas Approach

Abstract Background Over the last years, genome-wide association studies (GWAS) based on imputed whole-genome sequences (WGS) have been used to detect quantitative trait loci (QTL) and highlight candidate genes for important traits. However, in general this approach does not allow to validate the effects of candidate mutations or determine if they are truly causative for the trait(s) in question. To address these questions, we applied a two-step, within-breed GWAS approach on 15 traits (5 linked with milk production, 2 with udder health, and 8 with udder morphology) in Montbéliarde (MON), Normande (NOR), and Holstein (HOL) cattle. We detected the most-promising candidate variants (CV) using imputed WGS of 2515 MON, 2203 NOR, and 6321 HOL bulls, and validated their effects in three younger populations of 23,926 MON, 9400 NOR, and 51,977 HOL cows. Results Bull sequence-based GWAS detected 84 QTL: 13, 10, and 30 for milk production traits; 3, 0, and 2 for somatic cell score (SCS); and 8, 2 and 16 for udder morphology traits, in MON, NOR, and HOL respectively. Five genomic regions with effects on milk production traits were shared among the three breeds whereas six (2 for production and 4 for udder morphology and health traits) had effects in two breeds. In 80 of these QTL, 855 CV were highlighted based on the significance of their effects and functional annotation. The subsequent GWAS on MON, NOR, and HOL cows validated 8, 9, and 23 QTL for production traits; 0, 0, and 1 for SCS; and 4, 1, and 8 for udder morphology traits, respectively. In 47 of the 54 confirmed QTL, the CV identified in bulls had more significant effects than single nucleotide polymorphisms (SNPs) from the standard 50K chip. The best CV for each validated QTL was located in a gene that was functionally related to production (36 QTL) or udder (9 QTL) traits. Conclusions Using this two-step GWAS approach, we identified and validated 54 QTL that included CV mostly located within functional candidate genes and explained up to 6.3% (udder traits) and 37% (production traits) of the genetic variance of economically important dairy traits. These CV are now included in the chip used to evaluate French dairy cattle and can be integrated into routine genomic evaluation.

scholarly journals Efficient Haplotype Block Partitioning and Tag SNP Selection Algorithms under Various Constraints

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Wen-Pei Chen ◽  
Che-Lun Hung ◽  
Yaw-Ling Lin
Keyword(s):  
Linkage Disequilibrium ◽  
Haplotype Block ◽  
Association Studies ◽  
Optimal Solution ◽  
High Linkage Disequilibrium ◽  
Chromosome 21 ◽  
Small Subset ◽  
Genome Wide Association Studies ◽  
Block Partitioning ◽  
Tag Snps

Patterns of linkage disequilibrium plays a central role in genome-wide association studies aimed at identifying genetic variation responsible for common human diseases. These patterns in human chromosomes show a block-like structure, and regions of high linkage disequilibrium are called haplotype blocks. A small subset of SNPs, called tag SNPs, is sufficient to capture the haplotype patterns in each haplotype block. Previously developed algorithms completely partition a haplotype sample into blocks while attempting to minimize the number of tag SNPs. However, when resource limitations prevent genotyping all the tag SNPs, it is desirable to restrict their number. We propose two dynamic programming algorithms, incorporating many diversity evaluation functions, for haplotype block partitioning using a limited number of tag SNPs. We use the proposed algorithms to partition the chromosome 21 haplotype data. When the sample is fully partitioned into blocks by our algorithms, the 2,266 blocks and 3,260 tag SNPs are fewer than those identified by previous studies. We also demonstrate that our algorithms find the optimal solution by exploiting the nonmonotonic property of a common haplotype-evaluation function.

scholarly journals Causal Haplotype Block Identification in Plant Genome-Wide Association Studies

2021 ◽  
Author(s):  
Xing Wu ◽  
Wei Jiang ◽  
Christopher Fragoso ◽  
Jing Huang ◽  
Geyu Zhou ◽  
...  
Keyword(s):  
Fine Mapping ◽  
Complex Traits ◽  
Haplotype Block ◽  
Association Studies ◽  
Crop Improvement ◽  
Plant Genome ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Haplotype Blocks ◽  
Genome Wide

Genome wide association studies (GWAS) can play an essential role in understanding genetic basis of complex traits in plants and animals. Conventional SNP-based linear mixed models (LMM) used in many GWAS that marginally test single nucleotide polymorphisms (SNPs) have successfully identified many loci with major and minor effects. In plants, the relatively small population size in GWAS and the high genetic diversity found many plant species can impede mapping efforts on complex traits. Here we present a novel haplotype-based trait fine-mapping framework, HapFM, to supplement current GWAS methods. HapFM uses genotype data to partition the genome into haplotype blocks, identifies haplotype clusters within each block, and then performs genome-wide haplotype fine-mapping to infer the causal haplotype blocks of trait. We benchmarked HapFM, GEMMA, BSLMM, and GMMAT in both simulation and real plant GWAS datasets. HapFM consistently resulted in higher mapping power than the other GWAS methods in simulations with high polygenicity. Moreover, it resulted in higher mapping resolution, especially in regions of high LD, by identifying small causal blocks in the larger haplotype block. In the Arabidopsis flowering time (FT10) datasets, HapFM identified four novel loci compared to GEMMA results, and its average mapping interval of HapFM was 9.6 times smaller than that of GEMMA. In conclusion, HapFM is tailored for plant GWAS to result in high mapping power on complex traits and improved mapping resolution to facilitate crop improvement.

scholarly journals Association ofTNFAIP3Polymorphism with Susceptibility to Systemic Lupus Erythematosus in a Japanese Population

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Aya Kawasaki ◽  
Ikue Ito ◽  
Satoshi Ito ◽  
Taichi Hayashi ◽  
Daisuke Goto ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Japanese Population ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Allelic Association ◽  
Genome Wide Association Studies ◽  
Mrna Levels ◽  
Nucleotide Polymorphisms ◽  
Systemic Lupus

Recent genome-wide association studies demonstrated association of single nucleotide polymorphisms (SNPs) in theTNFAIP3region at 6q23 with systemic lupus erythematosus (SLE) in European-American populations. In this study, we investigated whether SNPs in theTNFAIP3region are associated with SLE also in a Japanese population. A case-control association study was performed on the SNPs rs13192841, rs2230926, and rs6922466 in 318 Japanese SLE patients and 444 healthy controls. Association of rs2230926 G allele with SLE was replicated in Japanese (allelic associationP=.033, odds ratio [OR] 1.47, recessive modelP=.023, OR 8.52). The association was preferentially observed in the SLE patients with nephritis. When theTNFAIP3mRNA levels of the HapMap samples were examined using GENEVAR database, the presence ofTNFAIP3rs2230926 G allele was associated with lower mRNA expression ofTNFAIP3(P=.013). These results indicated thatTNFAIP3is a susceptibility gene to SLE both in the Caucasian and Asian populations.

scholarly journals Dynamics of Associations Between Single Nucleotide Polymorphisms in Relation to Alzheimer's Disease Captured with a New Measure of Linkage Disequilibrium

2018 ◽  
Vol 4 (2) ◽  
pp. 100045 ◽  
Author(s):  
Stanislav J. Sys ◽  
David Fournier ◽  
Illia Horenko ◽  
Kristina Endres ◽  
Susanne Gerber
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Linkage Disequilibrium ◽  
Single Nucleotide Polymorphisms ◽  
Latent Variables ◽  
Association Studies ◽  
Point Mutations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Genome-Wide-Association-Studies have become a powerful method to link point mutations (e.g. single nucleotide polymorphisms (SNPs)) to a certain phenotype or a disease. However, their power to detect SNPs associated to polygenic diseases such as Alzheimer's Disease (AD) is limited, since they can only infer the pairwise relation of single SNPs to the phenotype and ignore possible effects of various SNP combinations. The common method to probe these possible complex genetic patterns is to compute a measure called linkage disequilibrium (LD). Despite the fact that several predictive patterns found with LD could successfully be applied to medical diagnosis, this measure still holds several drawbacks as for example the difficulty to confirm and replicate experimental results as well as its sensitivity to statistical biases. Here, we present the application of an alternative method, Linkage Probability (LP) for genetic pattern identification that provides the posterior probability of a relation between two categorical data sets and simultaneously considers potential biases from latent variables, such as the recombination rate or the genetic structure of a population. By applying the LP framework to data from the ADSP-Project, we show that changes of linkage patterns between SNPs can be associated to Alzheimer's disease. Common genomic relation measures still fail to extract this link.

scholarly journals Identification of genomic regions affecting production traits in pigs divergently selected for feed efficiency

2020 ◽  
Author(s):  
Emilie Delpuech ◽  
Amir Aliakbari ◽  
Yann Labrune ◽  
Katia Fève ◽  
Yvon Billon ◽  
...  
Keyword(s):  
Feed Efficiency ◽  
Production Systems ◽  
Agronomic Traits ◽  
Association Studies ◽  
Pedigree Information ◽  
Strong Impact ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Production Traits ◽  
Genomic Regions

AbstractBackgroundFeed efficiency is a major driver of the sustainability of pig production systems. Understanding biological mechanisms underlying these agronomic traits is an important issue whether for environment and farms economy. This study aimed at identifying genomic regions affecting residual feed intake (RFI) and other production traits in two pig lines divergently selected for RFI during 9 generations (LRFI, low RFI; HRFI, high RFI).ResultsWe built a whole dataset of 570,447 single nucleotide polymorphisms (SNPs) in 2,426 pigs with records for 24 production traits after both imputation and prediction of genotypes using pedigree information. Genome-wide association studies (GWAS) were performed including both lines (Global-GWAS) or each line independently (LRFI-GWAS and HRFI-GWAS). A total of 54 chromosomic regions were detected with the Global-GWAS, whereas 37 and 61 regions were detected in LRFI-GWAS and HRFI-GWAS, respectively. Among those, only 15 regions were shared between at least two analyses, and only one was common between the three GWAS but affecting different traits. Among the 12 QTL detected for RFI, some were close to QTL detected for meat quality traits and 9 pinpointed novel genomic regions for some harbored candidate genes involved in cell proliferation and differentiation processes of gastrointestinal tissues or lipid metabolism-related signaling pathways. Detection of mostly different QTL regions between the three designs suggests the strong impact of the dataset on the detection power, which could be due to the changes of allelic frequencies during the line selection.ConclusionsBesides efficiently detecting known and new QTL regions for feed efficiency, the combination of GWAS carried out per line or simultaneously using all individuals highlighted the identification of chromosomic regions under selection that affect various production traits.

Sign in / Sign up

Export Citation Format

Share Document