Dataset Information

Linkage Analysis and Haplotype Phasing in Experimental Autopolyploid Populations with High Ploidy Level Using Hidden Markov Models.

ABSTRACT: Modern SNP genotyping technologies allow measurement of the relative abundance of different alleles for a given locus and consequently estimation of their allele dosage, opening a new road for genetic studies in autopolyploids. Despite advances in genetic linkage analysis in autotetraploids, there is a lack of statistical models to perform linkage analysis in organisms with higher ploidy levels. In this paper, we present a statistical method to estimate recombination fractions and infer linkage phases in full-sib populations of autopolyploid species with even ploidy levels for a set of SNP markers using hidden Markov models. Our method uses efficient two-point procedures to reduce the search space for the best linkage phase configuration and reestimate the final parameters by maximizing the likelihood of the Markov chain. To evaluate the method, and demonstrate its properties, we rely on simulations of autotetraploid, autohexaploid and autooctaploid populations and on a real tetraploid potato data set. The results show the reliability of our approach, including situations with complex linkage phase scenarios in hexaploid and octaploid populations.

SUBMITTER: Mollinari M

PROVIDER: S-EPMC6778803 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Linkage Analysis and Haplotype Phasing in Experimental Autopolyploid Populations with High Ploidy Level Using Hidden Markov Models.

Mollinari Marcelo M Garcia Antonio Augusto Franco AAF

G3 (Bethesda, Md.) 20191007 10

Modern SNP genotyping technologies allow measurement of the relative abundance of different alleles for a given locus and consequently estimation of their allele dosage, opening a new road for genetic studies in autopolyploids. Despite advances in genetic linkage analysis in autotetraploids, there is a lack of statistical models to perform linkage analysis in organisms with higher ploidy levels. In this paper, we present a statistical method to estimate recombination fractions and infer linkage ...[more]

PMID: 31405891

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Project description:Linkage disequilibrium (LD) analysis provides information on the evolutionary aspects of populations. Recently, haplotype blocks have been used to increase the power of quantitative trait loci detection in genome-wide association studies and the prediction accuracy of genomic selection. Our objectives were as follows: to compare the degree of LD, LD decay, and LD decay extent in popcorn populations; to characterize the number and length of haplotype blocks in the populations; and to determine whether maize chromosomes also have a pattern of interspaced regions of high and low rates of recombination. We used a biparental population, a synthetic, and a breeding population, genotyped for approximately 75,000 single nucleotide polymorphisms (SNPs). The sample size ranged from 190 to 192 plants. For the whole-genome LD and haplotype block analyses, we assumed a window of 500 kb. To characterize the block and step patterns of LD in the populations, we constructed LD maps by chromosome, defining a cold spot as a chromosome segment including SNPs with the same LDU position. The LD and haplotype block analyses were also performed at the intragenic level, selecting 12 genes related to zein, starch, cellulose, and fatty acid biosynthesis. The populations with the higher and lower frequencies of |D'| values greater than 0.75 were the biparental (65-74%) and the breeding population (26-58%), respectively. There were slight differences between the populations regarding the average distance for SNPs with |D'| values greater than 0.75 (in the range of approximately 207 to 229 kb). The level of LD expressed by the r2 values was low in the populations (0.02, 0.04, and 0.04, on average) but comparable to some non-isolated human populations. The frequency of r2 values greater than 0.75 was lower in the biparental population (0.2-0.5%) and higher in the other populations (0.2-1.6%). The average distance for SNPs with r2 values greater than 0.75 was much higher in the biparental population (approximately 80 to 126 kb). In the other populations, the ranges were approximately 6 to 19 and 6 to 35 kb. The heatmaps for the regions covered by the first 100 SNPs in each chromosome, in each population (1 to 3.3 Mb, approximately), provided evidence that the comparatively few high r2 values (close to 1.0) occurred only for SNPs in close proximity, especially in the synthetic and breeding populations. Due to the reduced number of SNPs in the haplotype blocks (2 to 3) in the populations, it is not expected advantage of a haplotype-based association study as well as genomic selection along generations. 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. The LD maps indicate that maize chromosomes had a pattern of regions of extensive LD interspaced with regions of low LD. However, our simulated LD map provides evidence that this pattern can reflect regions with differences in allele frequencies and LD levels (expressed by |D'|) and not regions with high and low rates of recombination.

Project description:BackgroundKnowledge of phase, the specific allele sequence on each copy of homologous chromosomes, is increasingly recognized as critical for detecting certain classes of disease-associated mutations. One approach for detecting such mutations is through phased haplotype association analysis. While the accuracy of methods for phasing genotype data has been widely explored, there has been little attention given to phasing accuracy at haplotype block scale. Understanding the combined impact of the accuracy of phasing tool and the method used to determine haplotype blocks on the error rate within the determined blocks is essential to conduct accurate haplotype analyses.ResultsWe present a systematic study exploring the relationship between seven widely used phasing methods and two common methods for determining haplotype blocks. The evaluation focuses on the number of haplotype blocks that are incorrectly phased. Insights from these results are used to develop a haplotype estimator based on a consensus of three tools. The consensus estimator achieved the most accurate phasing in all applied tests. Individually, EAGLE2, BEAGLE and SHAPEIT2 alternate in being the best performing tool in different scenarios. Determining haplotype blocks based on linkage disequilibrium leads to more correctly phased blocks compared to a sliding window approach. We find that there is little difference between phasing sections of a genome (e.g. a gene) compared to phasing entire chromosomes. Finally, we show that the location of phasing error varies when the tools are applied to the same data several times, a finding that could be important for downstream analyses.ConclusionsThe choice of phasing and block determination algorithms and their interaction impacts the accuracy of phased haplotype blocks. This work provides guidance and evidence for the different design choices needed for analyses using haplotype blocks. The study highlights a number of issues that may have limited the replicability of previous haplotype analysis.

Dataset Information

Linkage Analysis and Haplotype Phasing in Experimental Autopolyploid Populations with High Ploidy Level Using Hidden Markov Models.

Publications

Linkage Analysis and Haplotype Phasing in Experimental Autopolyploid Populations with High Ploidy Level Using Hidden Markov Models.

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