Integrated analysis of whole genome and transcriptome sequencing reveals a frameshift mutation associated with
1National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Abstract:
Embryo loss is an important factor affecting fertility in dairy production. HH2 was identified as a haplotype on chromosome 1 associated with embryonic lethality in Holstein cattle. In the current study, both short- and long-read WGS was performed on four carriers and four non-carriers of HH2 to screen for variants in concordance with HH2 haplotype status. Sequence variation analysis revealed five putative functional variants of protein-coding genes, including a frameshift mutation (g.107172616delT) in intraflagellar transport protein 80 (IFT80) gene. Transcriptome analysis of whole blood indicated that no gene exhibited significantly differential expression or allele-specific expression between carriers and non-carriers 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-throughput sequencing technologies is an efficient strategy to screen for the candidate causative mutations responsible for Mendelian traits, including genetic disorders.
More Related Videos
11:27Efficient Production and Identification of CRISPR/Cas9-generated Gene Knockouts in the Model System Danio rerio
Published on: August 28, 2018
09:04Transcriptome Profiling of In-Vivo Produced Bovine Pre-implantation Embryos Using Two-color Microarray Platform
Published on: January 30, 2017
Related Concept Videos
01:30Point and Frameshift Mutations
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:09Epistasis Analysis