Skip to Main content Skip to Navigation
Journal articles

Genome-wide next-generation DNA and RNA sequencing reveals a mutation that perturbs splicing of the phosphatidylinositol glycan anchor biosynthesis class H gene (PIGH) and causes arthrogryposis in Belgian Blue cattle

Abstract : Cattle populations are characterized by regular outburst of genetic defects as a result of the extensive use of elite sires. The causative genes and mutations can nowadays be rapidly identified by means of genome-wide association studies combined with next generation DNA sequencing, provided that the causative mutations are conventional loss-of-function variants. We show in this work how the combined use of next generation DNA and RNA sequencing allows for the rapid identification of otherwise difficult to identify splice-site variants. We report the use of haplotype-based association mapping to identify a locus on bovine chromosome 10 that underlies autosomal recessive arthrogryposis in Belgian Blue Cattle. We identify 31 candidate mutations by resequencing the genome of four cases and 15 controls at ~10-fold depth. By analyzing RNA-Seq data from a carrier fetus, we observe skipping of the second exon of the PIGH gene, which we confirm by RT-PCR to be fully penetrant in tissues from affected calves. We identify - amongst the 31 candidate variants - a C-to-G transversion in the first intron of the PIGH gene (c211-10C > G) that is predicted to affect its acceptor splice-site. The resulting PIGH protein is likely to be non-functional as it lacks essential domains, and hence to cause arthrogryposis. This work illustrates how the growing arsenal of genome exploration tools continues to accelerate the identification of an even broader range of disease causing mutations, therefore improving the management and control of genetic defects in livestock.
Complete list of metadata

Cited literature [16 references]  Display  Hide  Download

https://hal.inrae.fr/hal-02635877
Contributor : Migration Prodinra Connect in order to contact the contributor
Submitted on : Wednesday, May 27, 2020 - 7:07:25 PM
Last modification on : Thursday, August 5, 2021 - 3:41:02 AM

File

2015_Sartelet A_BMC Genomics_1...
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Arnaud Sartelet, Wanbo Li, Eric Pailhoux, Christophe Richard, Nico Tamma, et al.. Genome-wide next-generation DNA and RNA sequencing reveals a mutation that perturbs splicing of the phosphatidylinositol glycan anchor biosynthesis class H gene (PIGH) and causes arthrogryposis in Belgian Blue cattle. BMC Genomics, BioMed Central, 2015, 16, pp.1-9. ⟨10.1186/s12864-015-1528-y⟩. ⟨hal-02635877⟩

Share

Metrics

Record views

38

Files downloads

75