SPEARS: Standard Performance Evaluation of Ancestral haplotype Reconstruction through Simulation

Motivation Ancestral haplotype maps provide useful information about genomic variation and insights into biological processes. Reconstructing the descendent haplotype structure of homologous chromosomes, particularly for large numbers of individuals, can help with characterizing the recombination landscape, elucidating genotype-to-phenotype relationships, improving genomic predictions and more. Inferring haplotype maps from sparse genotype data is an efficient approach to whole-genome haplotyping, but this is a non-trivial problem. A standardized approach is needed to validate whether haplotype reconstruction software, conceived population designs and existing data for a given population provides accurate haplotype information for further inference. Results We introduce SPEARS, a pipeline for the simulation-based appraisal of genome-wide haplotype maps constructed from sparse genotype data. Using a specified pedigree, the pipeline generates virtual genotypes (known data) with genotyping errors and missing data structure. It then proceeds to mimic analysis in practice, capturing sources of error due to genotyping, imputation and haplotype inference. Standard metrics allow researchers to assess different population designs and which features of haplotype structure or regions of the genome are sufficiently accurate for analysis. Haplotype maps for 1000 outcross progeny from a multi-parent population of maize are used to demonstrate SPEARS. Availabilityand implementation SPEARS, the protocol and suite of scripts, are publicly available under an MIT license at GitHub (https://github.com/maizeatlas/spears).. Supplementary information Supplementary data are available at Bioinformatics online.

SPEARS: Standard Performance Evaluation of Ancestral Reconstruction through Simulation

MotivationAncestral haplotype maps provide useful information about genomic variation and biological processes. Reconstructing the descendent haplotype structure of homologous chromosomes, particularly for large numbers of individuals, can help with characterizing the recombination landscape, elucidating genotype-to-phenotype relationships, improving genomic predictions and more. Inferring haplotype maps from sparse genotype data is an efficient approach to whole-genome haplotyping, but this is a non-trivial problem. A standardized approach is needed to validate whether haplotype reconstruction software, conceived population designs and existing data for a given population provides accurate haplotype information for further inference.ResultsWe introduce SPEARS, a pipeline for whole simulation-based appraisal of genome-wide ancestral haplotype inference. The pipeline generates virtual genotypes (truth data) with real-world missing data structure. It then proceeds to mimic analysis in practice, capturing sources of error due to imputation and reconstruction of ancestral haplotypes. Standard metrics allow researchers to assess which features of haplotype structure or regions of the genome are sufficiently accurate for analysis and reporting. Haplotype maps for 1,000 outcross progeny from a multi-parent population of maize is used to demonstrate SPEARS.Availabilityhttps://github.com/maizeatlas/spears

Meiotically and Mitotically Stable Inheritance of DNA Hypomethylation Induced by ddm1 Mutation of Arabidopsis thaliana

In contrast to mammalian epigenetic phenomena, where resetting of gene expression generally occurs in each generation, epigenetic states of plant genes are often stably transmitted through generations. The Arabidopsis mutation ddm1 causes a 70% reduction in genomic 5-methylcytosine level. We have previously shown that the ddm1 mutation results in an accumulation of a variety of developmental abnormalities by slowly inducing heritable changes in other loci. Each of the examined ddm1-induced developmental abnormalities is stably transmitted even when segregated from the potentiating ddm1 mutation. Here, the inheritance of DNA hypomethylation induced by ddm1 was examined in outcross progeny by HPLC and Southern analyses. The results indicate that (i) DDM1 gene function is not necessary during the gametophyte stage, (ii) ddm1 mutation is completely recessive, and (iii) remethylation of sequences hypomethylated by the ddm1 mutation is extremely slow or nonexistent even in wild-type DDM1 backgrounds. The stable transmission of DNA methylation status may be related to the meiotic heritability of the ddm1-induced developmental abnormalities.