title: Using Mendelian inheritance to improve high-throughput SNP discovery.
abstract: Restriction site-associated DNA sequencing or genotyping-by-sequencing (GBS) approaches allow for rapid and cost-effective discovery and genotyping of thousands of single-nucleotide polymorphisms (SNPs) in multiple individuals. However, rigorous quality control practices are needed to avoid high levels of error and bias with these reduced representation methods. We developed a formal statistical framework for filtering spurious loci, using Mendelian inheritance patterns in nuclear families, that accommodates variable-quality genotype calls and missing data--both rampant issues with GBS data--and for identifying sex-linked SNPs. Simulations predict excellent performance of both the Mendelian filter and the sex-linkage assignment under a variety of conditions. We further evaluate our method by applying it to real GBS data and validating a subset of high-quality SNPs. These results demonstrate that our metric of Mendelian inheritance is a powerful quality filter for GBS loci that is complementary to standard coverage and Hardy-Weinberg filters. The described method, implemented in the software MendelChecker, will improve quality control during SNP discovery in nonmodel as well as model organisms.
authors.affiliation: Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, New York 14853 Cornell Laboratory of Ornithology, Cornell University, Ithaca, New York 14853 nc276@cornell.edu.
authors.forename: Nancy
authors.identifier: http://orcid.org/0000-0001-8966-3449
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
authors.forename: Cristopher V
authors.identifier: http://orcid.org/0000-0001-9689-5344
authors.initials: CV
authors.lastname: Van Hout
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Gottipati
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
mesh_terms: D000818:Animals; D003198:Computer Simulation; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D040582:Inheritance Patterns / Q000235:genetics*; D046109:Passeriformes / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D012984:Software
keywords: Mendelian inheritance; RAD-seq; SNP discovery; genotyping-by-sequencing; pedigrees