A frameshift variant in the COL5A1 gene in a cat with Ehlers‐Danlos syndrome

Abstract

Ehlers-Danlos syndrome (EDS) is a group of heritable connective tissue disorders caused by defective collagen synthesis or incorrect assembly of the collagen triple helical structure. EDS is characterised by joint hypermobility, skin hyperextensibility, abnormal scarring, poor wound healing and tissue friability. Human EDS may be caused by variants in several different genes including COL5A1, which encodes the collagen type V alpha 1 chain. For the present study we investigated a 1.5-year-old, spayed female, domestic shorthair cat with EDS. The affected cat showed multiple recurrent skin tears, hyperextensibility of the skin and joint abnormalities. We obtained whole genome sequencing data from the affected cat and searched for variants in candidate genes known to cause EDS. We detected a heterozygous single base-pair deletion in exon 43 of the COL5A1 gene, namely c.3420delG. The deletion was predicted to result in a frameshift and premature stop codon: p.(Leu1141SerfsTer134). Sanger sequencing confirmed that the variant was present in the affected cat and absent from 103 unaffected cats from different breeds. The variant was also absent from a Burmese cat with EDS. Based on knowledge about the functional impact of COL5A1 variants in other species, COL5A1: c.3420delG represents a compelling candidate causative variant for the observed EDS in the affected cat.

Transcriptome analysis identifies genes involved with the development of umbilical hernias in pigs

“…Tajima et al (1999) [78], demonstrated that deficiency in the EPYC gene could cause Ehlers-Danlos syndrome in Dutch breed calves. This hereditary syndrome causes a defect in the connective tissue, due to changes in collagen synthesis and/or assembly of the collagen structure [79][80][81]. Due to the problems in the fibrillar collagen, the skin becomes fragile and with high risk of rupture [81].…”

“…This hereditary syndrome causes a defect in the connective tissue, due to changes in collagen synthesis and/or assembly of the collagen structure [79][80][81]. Due to the problems in the fibrillar collagen, the skin becomes fragile and with high risk of rupture [81]. Several studies have associated this syndrome with defects in collagen production [82], however, the actual function of the EPYC is not yet well known in pigs.…”

A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism

“…Once coupled with the quickly advancing sequencing technology and exploitable results, genomic medicine in companion animals promises to expand the comparative knowledge of mechanisms of action across species. Despite the continuing successful discovery of feline disease variants using both candidate gene and whole genome sequencing (WGS) approaches [1,[12][13][14][15], the understanding of normal and disease sequence variation in the domestic cat and interrogation of gene structure and function is limited by an incomplete genome assembly.…”

A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism

“…Using this Felis_catus_9.0 assembly, a vast new repertoire of SNVs and SVs were discovered 30 for the domestic cat. The total number of variants discovered across our diverse collection of 31 domestic cats was substantially higher than previous studies in other mammals, such as, cow 32 [36], dog [37], rat [38][39][40], sheep [41,42], pig [43], and horse [44]. Even rhesus macaques, with 1 twice as many variants as human, do not approach the same levels of cat SNV variation [45, 2 46].…”