Best practices for analyzing imputed genotypes from low-pass sequencing in dogs

	Best practices for analyzing imputed genotypes from low-pass sequencing in dogs
	Buckley, RM; Harris, AC; Wang, GD; Whitaker, DT; Zhang, YP; Ostrander, EA
	2022
发表期刊	MAMMALIAN GENOME
ISSN	0938-8990
卷号	33 期号:1 页码:213-229
摘要	Although DNA array-based approaches for genome-wide association studies (GWAS) permit the collection of thousands of low-cost genotypes, it is often at the expense of resolution and completeness, as SNP chip technologies are ultimately limited by SNPs chosen during array development. An alternative low-cost approach is low-pass whole genome sequencing (WGS) followed by imputation. Rather than relying on high levels of genotype confidence at a set of select loci, low-pass WGS and imputation rely on the combined information from millions of randomly sampled low-confidence genotypes. To investigate low-pass WGS and imputation in the dog, we assessed accuracy and performance by downsampling 97 high-coverage (> 15x) WGS datasets from 51 different breeds to approximately 1x coverage, simulating low-pass WGS. Using a reference panel of 676 dogs from 91 breeds, genotypes were imputed from the downsampled data and compared to a truth set of genotypes generated from high-coverage WGS. Using our truth set, we optimized a variant quality filtering strategy that retained approximately 80% of 14 M imputed sites and lowered the imputation error rate from 3.0% to 1.5%. Seven million sites remained with a MAF > 5% and an average imputation quality score of 0.95. Finally, we simulated the impact of imputation errors on outcomes for case-control GWAS, where small effect sizes were most impacted and medium-to-large effect sizes were minorly impacted. These analyses provide best practice guidelines for study design and data post-processing of low-pass WGS-imputed genotypes in dogs.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13402
专题	科研部门_分子进化与基因组多样性（张亚平）
推荐引用方式 GB/T 7714	Buckley, RM,Harris, AC,Wang, GD,et al. Best practices for analyzing imputed genotypes from low-pass sequencing in dogs[J]. MAMMALIAN GENOME,2022,33(1):213-229.
APA	Buckley, RM,Harris, AC,Wang, GD,Whitaker, DT,Zhang, YP,&Ostrander, EA.(2022).Best practices for analyzing imputed genotypes from low-pass sequencing in dogs.MAMMALIAN GENOME,33(1),213-229.
MLA	Buckley, RM,et al."Best practices for analyzing imputed genotypes from low-pass sequencing in dogs".MAMMALIAN GENOME 33.1(2022):213-229.

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