title: Estimation of inbreeding using pedigree, 50k SNP chip genotypes and full sequence data in three cattle breeds.
abstract: BACKGROUND
  Levels of inbreeding in cattle populations have increased in the past due to the use of a limited number of bulls for artificial insemination. High levels of inbreeding lead to reduced genetic diversity and inbreeding depression. Various estimators based on different sources, e.g., pedigree or genomic data, have been used to estimate inbreeding coefficients in cattle populations. However, the comparative advantage of using full sequence data to assess inbreeding is unknown. We used pedigree and genomic data at different densities from 50k to full sequence variants to compare how different methods performed for the estimation of inbreeding levels in three different cattle breeds.
  
  
  RESULTS
  Five different estimates for inbreeding were calculated and compared in this study: pedigree based inbreeding coefficient (F(PED)); run of homozygosity (ROH)-based inbreeding coefficients (F(ROH)); genomic relationship matrix (GRM)-based inbreeding coefficients (F(GRM)); inbreeding coefficients based on excess of homozygosity (F(HOM)) and correlation of uniting gametes (F(UNI)). Estimates using ROH provided the direct estimated levels of autozygosity in the current populations and are free effects of allele frequencies and incomplete pedigrees which may increase in inaccuracy in estimation of inbreeding. The highest correlations were observed between F(ROH) estimated from the full sequence variants and the F(ROH) estimated from 50k SNP (single nucleotide polymorphism) genotypes. The estimator based on the correlation between uniting gametes (F(UNI)) using full genome sequences was also strongly correlated with F(ROH) detected from sequence data.
  
  
  CONCLUSIONS
  Estimates based on ROH directly reflected levels of homozygosity and were not influenced by allele frequencies, unlike the three other estimates evaluated (F(GRM), F(HOM) and FU(NI)), which depended on estimated allele frequencies. F(PED) suffered from limited pedigree depth. Marker density affects ROH estimation. Detecting ROH based on 50k chip data was observed to give estimates similar to ROH from sequence data. In the absence of full sequence data ROH based on 50k can be used to access homozygosity levels in individuals. However, genotypes denser than 50k are required to accurately detect short ROH that are most likely identical by descent (IBD).
authors.affiliation: Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, DK-8830, Denmark. Qianqian.zhang@mbg.au.dk.|Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, Wageningen, 6700 AH, The Netherlands. Qianqian.zhang@mbg.au.dk.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, Wageningen, 6700 AH, The Netherlands. Mario.calus@wur.nl.
authors.forename: Mario P L
authors.initials: MP
authors.lastname: Calus
authors.affiliation: Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, DK-8830, Denmark. Bernt.guldbrandtsen@mbg.au.dk.
authors.forename: Bernt
authors.initials: B
authors.lastname: Guldbrandtsen
authors.affiliation: Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, DK-8830, Denmark. Mogens.Lund@mbg.au.dk.
authors.forename: Mogens S
authors.initials: MS
authors.lastname: Lund
authors.affiliation: Department of Molecular Biology and Genetics, Center for Quantitative Genetics and Genomics, Aarhus University, Tjele, DK-8830, Denmark. Goutam.sahana@mbg.au.dk.
authors.forename: Goutam
authors.initials: G
authors.lastname: Sahana
mesh_terms: D000465:Algorithms; D000483:Alleles; D000818:Animals; D002417:Cattle; D005787:Gene Frequency; D023281:Genomics / Q000379:methods; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D007178:Inbreeding; D008957:Models, Genetic; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide