Looking the Cow in the Eye: Deletion in the NID1 Gene Is Associated with Recessive Inherited Cataract in Romagnola Cattle

Abstract

Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed in Romagnola cattle. Pedigree analysis suggested a monogenic autosomal recessive inheritance. In addition to the cataract, one of the cases displayed abnormal head movements. Genome-wide association and homozygosity mapping and subsequent whole genome sequencing of a single case identified two perfectly associated sequence variants in a critical interval of 7.2 Mb on cattle chromosome 28: a missense point mutation located in an uncharacterized locus and an 855 bp deletion across the exon 19/intron 19 border of the bovine nidogen 1 (NID1) gene (c.3579_3604+829del). RT-PCR showed that NID1 is expressed in bovine lenses while the transcript of the second locus was absent. The NID1 deletion leads to the skipping of exon 19 during transcription and is therefore predicted to cause a frameshift and premature stop codon (p.1164fs27X). The truncated protein lacks a C-terminal domain essential for binding with matrix assembly complexes. Nidogen 1 deficient mice show neurological abnormalities and highly irregular crystal lens alterations. This study adds NID1 to the list of candidate genes for inherited cataract in humans and is the first report of a naturally occurring mutation leading to non-syndromic catarct in cattle provides a potential large animal model for human cataract.

A transposable element insertion in APOB causes cholesterol deficiency in Holstein cattle

“…The mapping to the UMD3.1 bovine reference genome assembly and variant calling were undertaken as previously described (Murgiano et al . ). Within the critical region of 2.24 Mb, a total of 3661 homozygous variants were identified in the affected calf.…”

“…Therefore, a search for extended regions of homozygosity with simultaneous allele sharing was performed as previously described (Murgiano et al . ), resulting in the discovery of 16 genome regions fulfilling these criteria (Fig. b).…”

Genetic Abnormalities in a Calf with Congenital Increased Muscular Tonus

“…The advent of next‐generation sequencing technology, in combination with the establishment of a reference genome sequence for domestic animal species, as for the bovine genome in 2009, has changed prospects enormously 8, 9, 10. Today, studying the molecular etiology of single cases is also feasible eg, in cattle10, 11, 17 as it is successfully performed in man since nearly 5 years now 18…”

Genomic variation across European cattle: contribution of gene flow

“…All the 19 individuals were paired-end re-sequenced with the Illumina sequencing technology (Illumina Inc.). We also obtained additional 18 WGS data (15 raw sequenced data and 3 WGS alignment) of several commercial and traditional cattle from previous studies (Bickhart et al, 2016;Daetwyler et al, 2014;Kim et al, 2017;Murgiano et al, 2014). All the detailed sample…”

“…Following library construction, all 19 DNA samples were paired-end re-sequenced with 150 bp read length using the Illumina sequencing technology (Illumina Inc.). An additional 10 WGS data (Table S1) of individuals representing several commercial and traditional cattle breeds were downloaded from the NCBI short read archive; all of these sequences were included in the data published previously (Bickhart et al, 2016a;Daetwyler et al, 2014;Kim et al, 2017;Murgiano et al, 2014).…”