Dataset Information

ELD: entropy-based linkage disequilibrium index between multiallelic sites.

ABSTRACT: Quantification of linkage disequilibrium (LD) is a critical step in studies investigating human genome variations. Commonly used LD indices such as r 2 handle LD of biallelic variants for two sites. As shown in a previously introduced LD index of ?, normalized entropy difference of the haplotype frequency between LD and linkage equilibrium (LE) could be utilized to estimate LD of biallelic variants for multiple sites. Here, we developed eLD (entropy-based Linkage Disequilibrium index between multiallelic sites) as publicly available software to calculate ? of multiallelic variants for two sites. Application of eLD could dissect complex LD structures among multiple HLA genes (e.g., strong LD among HLA-DRB1, HLA-DQA1, and HLA-DQB1 in East Asians). Use of eLD is not restricted to haplotype-based LD; it is also applicable to genotype-based LD. Therefore, eLD enables estimation of trans-regional LD of SNP genotypes at two unlinked loci, such as the nonlinear LD between functional missense variants of ADH1B (rs1229984 [Arg47His]) and ALDH2 (rs671 [Glu504Lys]).

SUBMITTER: Okada Y

PROVIDER: S-EPMC6197273 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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eLD: entropy-based linkage disequilibrium index between multiallelic sites.

Okada Yukinori Y

Human genome variation 20181022

Quantification of linkage disequilibrium (LD) is a critical step in studies investigating human genome variations. Commonly used LD indices such as r 2 handle LD of biallelic variants for two sites. As shown in a previously introduced LD index of ε, normalized entropy difference of the haplotype frequency between LD and linkage equilibrium (LE) could be utilized to estimate LD of biallelic variants for multiple sites. Here, we developed eLD (entropy-based < ...[more]

PMID: 30374405

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Project description:The aim of this study was to analyze the genomic homology between cattle (Bos taurus) and buffaloes (Bubalus bubalis) and to propose a rearrangement of the buffalo genome through linkage disequilibrium analyses of buffalo SNP markers referenced in the cattle genome assembly and also compare it to the buffalo genome assembly. A panel of bovine SNPs (single nucleotide polymorphisms) was used for hierarchical, non-hierarchical and admixture cluster analyses. Thus, the linkage disequilibrium information between markers of a specific panel of buffalo was used to infer chromosomal rearrangement. Haplotype diversity and imputation accuracy of the submetacentric chromosomes were also analyzed. The genomic homology between the species enabled us to use the bovine genome assembly to recreate a buffalo genomic reference by rearranging the submetacentric chromosomes. The centromere of the submetacentric chromosomes exhibited high linkage disequilibrium and low haplotype diversity. It allowed hypothesizing about chromosome evolution. It indicated that buffalo submetacentric chromosomes are a centric fusion of ancestral acrocentric chromosomes. The chronology of fusions was also suggested. Moreover, a linear regression between buffalo and cattle rearranged assembly and the imputation accuracy indicated that the rearrangement of the chromosomes was adequate. When using the bovine reference genome assembly, the rearrangement of the buffalo submetacentric chromosomes could be done by SNP BTA (chromosome of Bos taurus) calculations: shorter BTA (shorter arm of buffalo chromosome) was given as [(shorter BTA length - SNP position in shorter BTA)] and larger BTA length as [shorter BTA length + (larger BTA length - SNP position in larger BTA)]. Finally, the proposed linkage disequilibrium-based method can be applied to elucidate other chromosomal rearrangement events in other species with the possibility of better understanding the evolutionary relationship between their genomes.

Project description:BackgroundThe success of genome-wide scans depends on the strength and magnitude of linkage disequilibrium (LD) present within the populations under investigation. High density SNP arrays are currently in development for the sheep genome, however little is known about the behaviour of LD in this livestock species. This study examined the behaviour of LD within five sheep populations using two LD metrics, D' and x2'. Four economically important Australian sheep flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a crossbred population (Merino x Border Leicester), along with an inbred Australian Merino museum flock were analysed.ResultsShort range LD (0 - 5 cM) was observed in all five populations, however the persistence with increasing distance and magnitude of LD varied considerably between populations. Average LD (x2') for markers spaced up to 20 cM exceeded the non-syntenic average within the White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within the Merino and Merino x Border Leicester, with LD below or consistent with observed background levels. Using marker-marker LD as a guide to the behaviour of marker-QTL LD, estimates of minimum marker spacing were made. For a 95% probability of detecting QTL, a microsatellite marker would be required every 0.1 - 2.5 centimorgans, depending on the population used.ConclusionSheep populations were selected which were inbred (Macarthur Merino), highly heterogeneous (Merino) or intermediate between these two extremes. This facilitated analysis and comparison of LD (x2') between populations. The strength and magnitude of LD was found to differ markedly between breeds and aligned closely with both observed levels of genetic diversity and expectations based on breed history. This confirmed that breed specific information is likely to be important for genome wide selection and during the design of successful genome scans where tens of thousands of markers will be required.

Dataset Information

ELD: entropy-based linkage disequilibrium index between multiallelic sites.

Publications

eLD: entropy-based linkage disequilibrium index between multiallelic sites.

Similar Datasets

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