title: Quality control of genotypes using heritability estimates of gene content at the marker.
abstract: Quality control filtering of single-nucleotide polymorphisms (SNPs) is a key step when analyzing genomic data. Here we present a practical method to identify low-quality SNPs, meaning markers whose genotypes are wrongly assigned for a large proportion of individuals, by estimating the heritability of gene content at each marker, where gene content is the number of copies of a particular reference allele in a genotype of an animal (0, 1, or 2). If there is no mutation at the marker, gene content has an additive heritability of 1 by construction. The method uses restricted maximum likelihood (REML) to estimate heritability of gene content at each SNP and also builds a likelihood-ratio test statistic to test for zero error variance in genotyping. As a by-product, estimates of the allele frequencies of markers at the base population are obtained. Using simulated data with 10% permutation error (4% actual error) in genotyping, the method had a specificity of 0.96 (4% of correct markers are rejected) and a sensitivity of 0.99 (1% of wrong markers are accepted) if markers with heritability lower than 0.975 are discarded. Checking of Mendelian errors resulted in a lower sensitivity (0.84) for the same simulation. The proposed method is further illustrated with a real data set with genotypes from 3534 animals genotyped for 50,433 markers from the Illumina PorcineSNP60 chip and a pedigree of 6473 individuals; those markers underwent very little quality control. A total of 4099 markers with P-values lower than 0.01 were discarded based on our method, with associated estimates of heritability as low as 0.12. Contrary to other techniques, our method uses all information in the population simultaneously, can be used in any population with markers and pedigree recordings, and is simple to implement using standard software for REML estimation. Scripts for its use are provided.
authors.affiliation: Departamento de Producción Animal, Facultad de Agronomía, Universidad de Buenos Aires, C1417DSE Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1033AAJ Buenos Aires, Argentina.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Forneris
authors.affiliation: INRA, Génétique, Physiologie et Systèmes d'Elevage (GenPhySE), F-31326 Castanet-Tolosan, France Université de Toulouse, INP, ENSAT, Génétique, Physiologie et Systèmes d'Elevage (GenPhySE), F-31326 Castanet-Tolosan, France andres.legarra@toulouse.inra.fr.
authors.forename: Andres
authors.initials: A
authors.lastname: Legarra
authors.affiliation: INRA, Génétique, Physiologie et Systèmes d'Elevage (GenPhySE), F-31326 Castanet-Tolosan, France Université de Toulouse, INP, ENSAT, Génétique, Physiologie et Systèmes d'Elevage (GenPhySE), F-31326 Castanet-Tolosan, France.
authors.forename: Zulma G
authors.initials: ZG
authors.lastname: Vitezica
authors.affiliation: Animal and Dairy Science, University of Georgia, Athens, Georgia 30602.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tsuruta
authors.affiliation: Instituto Nacional de Investigación Agropecuaria, Canelones 90200, Uruguay.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aguilar
authors.affiliation: Animal and Dairy Science, University of Georgia, Athens, Georgia 30602.
authors.forename: Ignacy
authors.initials: I
authors.lastname: Misztal
authors.affiliation: Departamento de Producción Animal, Facultad de Agronomía, Universidad de Buenos Aires, C1417DSE Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Av. Rivadavia 1917, C1033AAJ Buenos Aires, Argentina.
authors.forename: Rodolfo J C
authors.initials: RJ
authors.lastname: Cantet
mesh_terms: D000818:Animals; D005819:Genetic Markers; D023281:Genomics / Q000592:standards*; D060005:Genotyping Techniques / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000592:standards; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011786:Quality Control; D012680:Sensitivity and Specificity; D034421:Sus scrofa
chemical_list: D005819:Genetic Markers
keywords: GenPred; REML; SNP; gene content; genomic selection; quality control; shared data resource