Revealing misassembled segments in the bovine reference genome by high resolution linkage disequilibrium scan.
Misassembly signatures, created by shuffling the order of sequences while assembling a genome, can be detected by the unexpected behavior of marker linkage disequilibrium (LD) decay. We developed a heuristic process to identify misassembly signatures, applied it to the bovine reference genome assembly (UMDv3.1) and presented the consequences of misassemblies in two case studies.



We identified 2,906 single nucleotide polymorphism (SNP) markers presenting unexpected LD decay behavior in 626 putative misassembled contigs, which comprised less than 1 % of the whole genome. Although this represents a small fraction of the reference sequence, these poorly assembled segments can lead to severe implications to local genome context. For instance, we showed that one of the misassembled regions mapped to the POLL locus, which affected the annotation of positional candidate genes in a GWAS case study for polledness in Nellore (Bos indicus beef cattle). Additionally, we found that poorly performing markers in imputation mapped to putative misassembled regions, and that correction of marker positions based on LD was capable to recover imputation accuracy.



This heuristic approach can be useful to cross validate reference assemblies and to filter out markers located at low confidence genomic regions before conducting downstream analyses.
Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista - UNESP, Campus de Jaboticabal, São Paulo, Brasil. adamtaiti@gmail.com.
Adam T H
AT
Utsunomiya
Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista - UNESP, Campus de Jaboticabal, São Paulo, Brasil.
Daniel J A
DJ
Santos
Nofima, Ås, Norway.
Solomon A
SA
Boison
Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista - UNESP, Campus de Jaboticabal, São Paulo, Brasil.
Yuri T
YT
Utsunomiya
Faculdade de Medicina Veterinária de Araçatuba, Universidade Estadual Paulista - UNESP, Campus de Araçatuba, São Paulo, Brasil.
Marco
M
Milanesi
Animal Genomics and Improvement Laboratory, ARS, USDA, Beltsville, MD, USA.
Derek M
DM
Bickhart
Institute of Zootechnics and Biodiversity and Ancient DNA Research Center, Università Cattolica del Sacro Cuore, Piacenza, Italy.|Nutrigenomics and Proteomics Research Center - PRONUTRIGEN, Università Cattolica del Sacro Cuore, Piacenza, Italy.
Paolo
P
Ajmone-Marsan
Department of Sustainable Agricultural Systems, Division of Livestock Sciences, BOKU - University of Natural Resources and Life Sciences, Vienna, Austria.
Johann
J
Sölkner
Faculdade de Medicina Veterinária de Araçatuba, Universidade Estadual Paulista - UNESP, Campus de Araçatuba, São Paulo, Brasil.|International Atomic Energy Agency (IAEA) Collaborating Centre on Animal Genomics and Bioinformatics, Araçatuba, São Paulo, Brasil.
José F
JF
Garcia
Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista - UNESP, Campus de Jaboticabal, São Paulo, Brasil.|Faculdade de Ciências Agrárias e Tecnológicas, Universidade Estadual Paulista - UNESP, Campus de Dracena, São Paulo, Brasil.
Ricardo
R
da Fonseca
Embrapa Gado de Leite, Juiz de Fora, Minas Gerais, Brasil. marcos.vb.silva@embrapa.br.
Marcos V G B
MV
da Silva
D000818:Animals; D002417:Cattle; D002874:Chromosome Mapping / Q000379:methods*; D019295:Computational Biology / Q000379:methods*; D016678:Genome; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D017422:Sequence Analysis, DNA / Q000379:methods
Bos indicus; Bos taurus; GWAS; Imputation; Linkage disequilibrium; Misassembly