Assessment of linkage disequilibrium patterns between structural variants and single nucleotide polymorphisms in three commercial chicken populations

Abstract BackgroundStructural variants (SV) are causative for some prominent phenotypic traits of livestock as different comb types in chickens or color patterns in pigs. Their effects on production traits are also increasingly studied. Nevertheless, accurately calling SV remains challenging. It is therefore of interest, whether close-by single nucleotide polymorphisms (SNPs) are in strong linkage disequilibrium (LD) with SVs and can serve as markers. Literature comes to different conclusions on whether SVs are in LD to SNPs on the same level as SNPs to other SNPs. The present study aimed to generate a precise SV callset from whole-genome short-read sequencing (WGS) data for three commercial chicken populations and to evaluate LD patterns between the called SV and surrounding SNPs.ResultsThe final callset consisted of 12,294,329 bivariate SNPs, 4,301 deletions (DEL), 224 duplications (DUP), 218 inversions (INV) and 117 translocation breakpoints (BND). While average LD between DELs and SNPs was at the same level as between SNPs and SNPs, LD between other SVs and SNPs was strongly reduced (DUP: 40 %, INV: 27 %, BND: 19 % of between-SNP LD). A main factor for the reduced LD was the presence of local minor allele frequency differences, which accounted for 50 % of the difference between SNP – SNP and DUP – SNP LD. This was potentially accompanied by lower genotyping accuracies for DUP, INV and BND compared with SNPs and DELs. An evaluation of the presence of tag SNPs (SNP in highest LD to the variant of interest) further revealed DELs to be slightly less tagged by WGS SNPs than WGS SNPs by other SNPs. This difference, however, was no longer present when reducing the pool of potential tag SNPs to SNPs located on four different chicken genotyping arrays.ConclusionsThe results imply that genomic variance due to DELs in the chicken populations studied can be captured by different SNP marker sets as good as variance from WGS SNPs, whereas separate SV calling might be advisable for DUP, INV, and BND effects.

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

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200028830 ◽

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.

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Linkage Disequilibrium Grouping of Single Nucleotide Polymorphisms (SNPs) Reflecting Haplotype Phylogeny for Efficient Selection of Tag SNPs

Genetics ◽

10.1534/genetics.104.038232 ◽

2005 ◽

Vol 170 (1) ◽

pp. 291-304 ◽

Cited By ~ 18

Author(s):

Fumihiko Takeuchi ◽

Kazuyuki Yanai ◽

Toshiyuki Morii ◽

Yuji Ishinaga ◽

Keiko Taniguchi-Yanai ◽

...

Keyword(s):

Linkage Disequilibrium ◽

Single Nucleotide Polymorphisms ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Tag Snps ◽

Efficient Selection ◽

Selection Of

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Protein Variation in ADH and ADH-RELATED in Drosophila pseudoobscura: Linkage Disequilibrium Between Single Nucleotide Polymorphisms and Protein Alleles

Genetics ◽

10.1093/genetics/159.2.673 ◽

2001 ◽

Vol 159 (2) ◽

pp. 673-687

Author(s):

Stephen W Schaeffer ◽

C Scott Walthour ◽

Donna M Toleno ◽

Anna T Olek ◽

Ellen L Miller

Keyword(s):

Linkage Disequilibrium ◽

Single Nucleotide Polymorphisms ◽

Drosophila Pseudoobscura ◽

Linkage Disequilibrium Mapping ◽

Nucleotide Polymorphisms ◽

Neutral Model ◽

Significant Linkage Disequilibrium ◽

Single Nucleotide ◽

Synonymous Sites ◽

Significant Linkage

Abstract A 3.5-kb segment of the alcohol dehydrogenase (Adh) region that includes the Adh and Adh-related genes was sequenced in 139 Drosophila pseudoobscura strains collected from 13 populations. The Adh gene encodes four protein alleles and rejects a neutral model of protein evolution with the McDonald-Kreitman test, although the number of segregating synonymous sites is too high to conclude that adaptive selection has operated. The Adh-related gene encodes 18 protein haplotypes and fails to reject an equilibrium neutral model. The populations fail to show significant geographic differentiation of the Adh-related haplotypes. Eight of 404 single nucleotide polymorphisms (SNPs) in the Adh region were in significant linkage disequilibrium with three ADHR protein alleles. Coalescent simulations with and without recombination were used to derive the expected levels of significant linkage disequilibrium between SNPs and 18 protein haplotypes. Maximum levels of linkage disequilibrium are expected for protein alleles at moderate frequencies. In coalescent models without recombination, linkage disequilibrium decays between SNPs and high frequency haplotypes because common alleles mutate to haplotypes that are rare or that reach moderate frequency. The implication of this study is that linkage disequilibrium mapping has the highest probability of success with disease-causing alleles at frequencies of 10%.

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Single nucleotide polymorphisms, haplotypes and combined genotypes of LAP3 gene in bovine and their association with milk production traits

Molecular Biology Reports ◽

10.1007/s11033-010-0524-1 ◽

2010 ◽

Vol 38 (6) ◽

pp. 4053-4061 ◽

Cited By ~ 28

Author(s):

Xue Zheng ◽

Zhihua Ju ◽

Ji Wang ◽

Qiuling Li ◽

Jinming Huang ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Milk Production ◽

Nucleotide Polymorphisms ◽

Production Traits ◽

Milk Production Traits ◽

Single Nucleotide ◽

Combined Genotypes

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Variation at the von Willebrand Factor (vWF) Gene Locus Is Associated With Plasma vWF:Ag Levels: Identification of Three Novel Single Nucleotide Polymorphisms in the vWF Gene Promoter

Blood ◽

10.1182/blood.v93.12.4277 ◽

1999 ◽

Vol 93 (12) ◽

pp. 4277-4283 ◽

Cited By ~ 74

Author(s):

Angela M. Keightley ◽

Y. Miu Lam ◽

Jolene N. Brady ◽

Cherie L. Cameron ◽

David Lillicrap

Keyword(s):

Single Nucleotide Polymorphisms ◽

Von Willebrand Factor ◽

Gene Locus ◽

Strong Linkage Disequilibrium ◽

Nucleotide Polymorphisms ◽

Polymorphic Variation ◽

Single Nucleotide ◽

Haplotype 1 ◽

Von Willebrand ◽

Willebrand Factor

Abstract Both genetic and environmental factors contribute to the normal population variability of plasma von Willebrand Factor (vWF) levels, however, regulatory mechanisms at the vWF gene locus itself have not yet been identified. We have investigated the association between polymorphic variation in the 5′-regulatory region of the vWF gene and levels of plasma vWF:Ag in a study of 261 group O blood donors. Three novel single nucleotide polymorphisms (SNPs) were identified in the vWF promoter: C/T at -1234, A/G at -1185, and G/A at -1051. These SNPs had identical allele frequencies of 0.36 for the -1234C, -1185A, and -1051G alleles and 0.64 for the -1234T, -1185G, and -1051A alleles and were in strong linkage disequilibrium. In fact, these polymorphisms segregated as two distinct haplotypes: -1234C/-1185A/-1051G (haplotype 1) and -1234T/-1185G/-1051A (haplotype 2) with 12.6% of subjects homozygous for haplotype 1, 40.6% homozygous for haplotype 2, and 42.5% of subjects heterozygous for both haplotypes. Only 4.3% of individuals had other genotypes. A significant association between promoter genotype and level of plasma vWF:Ag was established (analysis of covariance [ANCOVA], P = .008; Kruskal-Wallis test,P = .006); individuals with the CC/AA/GG genotype had the highest mean vWF:Ag levels (0.962 U/mL), intermediate values of vWF:Ag (0.867 U/mL) were observed for heterozygotes (CT/AG/GA), and those with the TT/GG/AA genotype had the lowest mean plasma vWF:Ag levels (0.776 U/mL). Interestingly, when the sample was subgrouped according to age, the significant association between promoter genotype and plasma vWF:Ag level was accentuated in subjects > 40 years of age (analysis of variance [ANOVA], P = .003; Kruskal-Wallis test, P= .001), but was not maintained for subjects ≤ 40 years of age (ANOVA, P > .4; Kruskal-Wallis test, P > .4). In the former subgroup, mean levels of plasma vWF:Ag for subjects with the CC/AA/GG, CT/AG/GA, and TT/GG/AA genotypes were 1.075, 0.954, and 0.794 U/mL, respectively. By searching a transcription factor binding site profile database, these polymorphic sequences were predicted to interact with several transcription factors expressed in endothelial cells, including Sp1, GATA-2, c-Ets, and NFκB. Furthermore, the binding sites at the -1234 and -1051 SNPs appeared to indicate allelic preferences for some of these proteins. Electrophoretic mobility shift assays (EMSAs) performed with recombinant human NFκB p50 showed preferential binding of the -1234T allele (confirmed by supershift EMSAs), and EMSAs using bovine aortic endothelial cell (BAEC) nuclear extracts produced specific binding of a nuclear protein to the -1051A allele, but not the -1051G allele. These findings suggest that circulating levels of vWF:Ag may be determined, at least in part, by polymorphic variation in the promoter region of the vWF gene, and that this association may be mediated by differential binding of nuclear proteins involved in the regulation of vWF gene expression.

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Progressive effects of single-nucleotide polymorphisms on 16 phenotypic traits based on longitudinal data

Genes & Genomics ◽

10.1007/s13258-019-00902-x ◽

2020 ◽

Vol 42 (4) ◽

pp. 393-403

Author(s):

Donghe Li ◽

Hahn Kang ◽

Sanghun Lee ◽

Sungho Won

Keyword(s):

Single Nucleotide Polymorphisms ◽

Longitudinal Data ◽

Density Lipoprotein ◽

Phenotypic Traits ◽

Chromosome 2 ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Longitudinal Changes ◽

Genome Wide ◽

A Genome

Abstract Background There are many research studies have estimated the heritability of phenotypic traits, but few have considered longitudinal changes in several phenotypic traits together. Objective To evaluate the progressive effect of single nucleotide polymorphisms (SNPs) on prominent health-related phenotypic traits by determining SNP-based heritability ($$h_{snp}^{2}$$hsnp2) using longitudinal data. Methods Sixteen phenotypic traits associated with major health indices were observed biennially for 6843 individuals with 10-year follow-up in a Korean community-based cohort. Average SNP heritability and longitudinal changes in the total period were estimated using a two-stage model. Average and periodic differences for each subject were considered responses to estimate SNP heritability. Furthermore, a genome-wide association study (GWAS) was performed for significant SNPs. Results Each SNP heritability for the phenotypic mean of all sixteen traits through 6 periods (baseline and five follow-ups) were significant. Gradually, the forced vital capacity in one second (FEV1) reflected the only significant SNP heritability among longitudinal changes at a false discovery rate (FDR)-adjusted 0.05 significance level ($$h_{snp}^{2} = 0.171$$hsnp2=0.171, FDR = 0.0012). On estimating chromosomal heritability, chromosome 2 displayed the highest heritability upon periodic changes in FEV1. SNPs including rs2272402 and rs7209788 displayed a genome-wide significant association with longitudinal changes in FEV1 (P = 1.22 × 10−8 for rs2272402 and P = 3.36 × 10−7 for rs7209788). De novo variants including rs4922117 (near LPL, P = 2.13 × 10−15) of log-transformed high-density lipoprotein (HDL) ratios and rs2335418 (near HMGCR, P = 3.2 $$\times$$× 10−9) of low-density lipoprotein were detected on GWAS. Conclusion Significant genetic effects on longitudinal changes in FEV1 among the middle-aged general population and chromosome 2 account for most of the genetic variance.

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