The extent of linkage disequilibrium in beef cattle breeds using high-density SNP genotypes
© Porto-Neto et al.; licensee BioMed Central Ltd. 2014
Received: 13 September 2013
Accepted: 1 March 2014
Published: 24 March 2014
The extent of linkage disequilibrium (LD) between molecular markers impacts genome-wide association studies and implementation of genomic selection. The availability of high-density single nucleotide polymorphism (SNP) genotyping platforms makes it possible to investigate LD at an unprecedented resolution. In this work, we characterised LD decay in breeds of beef cattle of taurine, indicine and composite origins and explored its variation across autosomes and the X chromosome.
In each breed, LD decayed rapidly and r2 was less than 0.2 for marker pairs separated by 50 kb. The LD decay curves clustered into three groups of similar LD decay that distinguished the three main cattle types. At short distances between markers (< 10 kb), taurine breeds showed higher LD (r2 = 0.45) than their indicine (r2 = 0.25) and composite (r2 = 0.32) counterparts. This higher LD in taurine breeds was attributed to a smaller effective population size and a stronger bottleneck during breed formation. Using all SNPs on only the X chromosome, the three cattle types could still be distinguished. However for taurine breeds, the LD decay on the X chromosome was much faster and the background level much lower than for indicine breeds and composite populations. When using only SNPs that were polymorphic in all breeds, the analysis of the X chromosome mimicked that of the autosomes.
The pattern of LD mirrored some aspects of the history of breed populations and showed a sharp decay with increasing physical distance between markers. We conclude that the availability of the HD chip can be used to detect association signals that remained hidden when using lower density genotyping platforms, since LD dropped below 0.2 at distances of 50 kb.
Linkage disequilibrium (LD) between molecular markers reflects the correlation between genotypes of two markers or the degree of non-random association between their alleles. Previous studies that used single nucleotide polymorphisms (SNPs) to describe patterns of LD in cattle at the whole-genome level[1–6] have suggested that 30 000 to 300 000 SNPs are necessary to perform a genome-wide association study (GWAS), depending on the trait studied and the statistical power desired[1, 2]. Today, the availability of high-density SNP platforms that can assay more than 0.5 million loci offers the required marker density.
The extent of LD has implications for both GWAS and the delivery of accurate genomic predictions. However, its importance is often neglected despite the fact that it is known that it can introduce bias. Collecting and using SNP genotyping data have exploded for cattle in the last few years due in part to decreasing genotyping cost and to efforts to improve cattle breeding through genomic selection. Despite this, few studies have documented the behaviour of LD using the expanded set of 777 000 SNPs available on the BovineHD platform (Illumina Inc, San Diego). One of the significant advances of this denser chip is that it allows for an accurate estimation of LD over short physical distances as it contains many more marker pairs separated by 10 kb or less.
Here, we present the LD decay curves for SNPs on bovine autosomes and the X chromosome for three genetic groups of cattle breeds: Bos taurus (taurine), Bos indicus (indicine) and a composite beef cattle group. The results were compared to an independent population to confirm and potentially generalize the findings. This report is intended to be used as an updated description of the extent of LD in beef cattle.
All analyses were performed using genotypes generated in previous work. Therefore, for this study, no animal ethics approval was requested because no new animals were sampled.
Description of samples and summary of results *
Nb of males
LD at 10 kb autos
LD at 10 kb BTAX
LD at 70 kb autos
LD at 70 kb BTAX
Bt × Bi
Bt × Bi
Bt × Bi
Bovine HapMap population
Bt × Bi
All animals were genotyped using the BovineHD SNP chip (Illumina, San Diego; http://www.illumina.com/documents/products/datasheets/datasheet_bovineHD.pdf) that includes 777 962 markers. Quality control and imputation of missing data in the Australian sample followed the pipeline described by Bolormaa et al.. Briefly, stringent filters were applied to each SNP (call rate, duplicated map position, extreme departure from Hardy-Weinberg equilibrium), resulting in 729 068 informative SNPs. Missing genotypes were imputed within each breed type using 30 iterations of the BEAGLE software. Genotypes for the same set of SNPs were extracted from the Bovine HapMap dataset but missing genotypes were not imputed. LD between each pair of SNPs, measured as r2, which is less susceptible to bias due to differences in allelic frequency, and within-breed genetic diversity (heterozygosity and proportion of polymorphic SNPs) were calculated using PLINK v1.07. For the X chromosome, two scenarios were explored: one including all markers, and the second including only fairly polymorphic markers with a minor allele frequency (MAF) greater than 0.1 in all breeds.
Results and discussion
A high proportion of polymorphic markers was observed across all breeds, with the taurine breeds showing a slightly lower proportion (Pn ~ 0.86) than their indicine and composite counterparts (Pn ~ 1.00 for both) (Table 1). Heterozygozity (He) ranged from 0.25 (Brahman from the HapMap dataset and Shorthorn) to 0.35 (Tropical Composite). In general, the composite breeds showed higher He (0.34) than the taurine (0.28) and indicine breeds (0.26) because they originated from a mixture of both these types of cattle.
To assess whether the results obtained here were a specific feature of the Australian population, we repeated the analyses with an independent sample of Angus, Santa Gertrudis and Brahman animals from the Bovine HapMap dataset[3, 10]. Results for all analyses on these populations showed high concordance with LD observed in the Australian populations for both the autosomes and BTAX (Figures 1 and2).
Our results expand on previous studies of genome-wide LD in bovine populations. By using larger samples and a much higher density of markers than before and by exploring variation across autosomes and the X chromosome, we obtained an exponential increase in pair-wise LD comparisons, which allowed us to produce robust results. Because LD dropped below 0.2 at marker distances above 50 kb, we conclude that the availability of the HD chip enables detection of association signals that remained hidden when using lower density genotyping platforms.
The authors acknowledge Tad S Sonstegard and Curtis P Van Tassell for facilitating access to the SNP genotypes from the Bovine HapMap population. Bolormaa Sunduimijid and Keith Savin are acknowledged for performing quality control of the SNP genotypes from the Australian population.
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