What type of study is this?

September 10, 2025Open Access

Rare phenotypes of white coat color in Simmental calves: genetic causes of syndromic forms of albinism and depigmentation

JJJoana G. P. JacintoUniversity of Bern TLT LeuenbergerUniversity of Bern MHMiriam HauserUniversity of Bern

Key Points

Investigation revealed three independent genetic variants related to syndromic disorders of coat color in Simmental calves.
Key findings include a likely pathogenic variant in TYR associated with oculocutaneous albinism in one calf and recessive inheritance across cases.
The study employed trio-based whole-genome sequencing to identify rare protein-changing variants, confirming results through Sanger sequencing.
Findings expand the understanding of pigmentation genetics in mammals, highlighting the need for further exploration of rare congenital disorders.

Abstract

The aim of this study was to investigate three unrelated Simmental calves with atypical white coat color, identify potential genetic causes using a trio-based whole-genome sequencing approach, and assess the prevalence of the identified variants in the breed. Several inherited alleles affecting coat color, ranging from fawn to red spotted and white-headed, have been described in Simmental cattle originating from Switzerland. However, no genetic variant has yet been associated with an almost completely white coat in this breed. Clinical examination revealed different syndromic disorders of white coat color in Simmental in all three cases, and pedigree records indicated recessive inheritance. Filtering for rare protein-changing variants revealed an independent homozygous variant that could be the cause in each case: a likely pathogenic missense variant in TYR (NP₈51344. 1: p. Pro428Leu) in case 1 with oculocutaneous albinism type 1, a likely pathogenic missense variant in GRID1 (XP₀24842694. 1: p. Pro489His) in case 2 with short stature-auditory depigmentation syndrome, and a frameshift variant of uncertain significance in RAD54B (NP₀01179884. 1: p. Ala722Gly724delinsAsnLeuIlePheCys*) in case 3 with a multisystem depigmentation syndrome. Validation by Sanger sequencing confirmed the variant genotypes, and parental heterozygosity supported recessive inheritance. These variants were almost entirely absent from other breeds, and the allele frequency of the three candidate causal variants was less than 1% in the current Swiss Simmental population. This study identified three novel recessive alleles associated with syndromic forms of albinism or depigmentation, revealing unexpected heterogeneity. The investigation did not reveal any indications of possible dominant de novo mutations impacting protein coding genes including known candidate genes for depigmentation phenotypes. These findings possibly expand the list of pigmentation related genes in mammals, but further investigation is needed. We also highlight the biomedical relevance of investigating rare congenital disorders in livestock.

KI fragen

Bookmark

View Full Paper