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HH2 was identified as a haplotype on chromosome 1 associated with embryonic lethality in Holstein cattle. In the current study, both short\u2010 and long\u2010read WGS was performed on four carriers and four non\u2010carriers of HH2 to screen for variants in concordance with HH2 haplotype status. Sequence variation analysis revealed five putative functional variants of protein\u2010coding genes, including a frameshift mutation (g.107172616delT) in intraflagellar transport protein 80 (<jats:italic>IFT80<\/jats:italic>) gene. Transcriptome analysis of whole blood indicated that no gene exhibited significantly differential expression or allele\u2010specific expression between carriers and non\u2010carriers in the candidate region. This evidence points to g.107172616delT as the highest priority causative mutation for HH2. Protein prediction reveals that the frameshift mutation results in a premature stop codon to reduce the peptide chain from 760 to 383 amino acids and greatly alters the structure and function of IFT80 protein. Our results demonstrate that the use of a combination of multiple high\u2010throughput sequencing technologies is an efficient strategy to screen for the candidate causative mutations responsible for Mendelian traits, including genetic disorders.<\/jats:p>","DOI":"10.1111\/age.13160","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T01:29:45Z","timestamp":1638840585000},"page":"137-141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Integrated analysis of whole genome and transcriptome sequencing reveals a frameshift mutation associated with recessive embryonic lethality in Holstein cattle"],"prefix":"10.1111","volume":"53","author":[{"given":"Y.","family":"Yang","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs College of Animal 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