Molecular characterization of the llama FGF5 gene and identification of putative loss of function mutations

Abstract

Llama, the most numerous domestic camelid in Argentina, has good fiber-production ability. Although a few genes related to other productive traits have been characterized, the molecular genetic basis of fiber growth control in camelids is still poorly understood. Fibroblast growth factor 5 (FGF5) is a secreted signaling protein that controls hair growth in humans and other mammals. Mutations in the FGF5 gene have been associated with long-hair phenotypes in several species. Here, we sequenced the llama FGF5 gene, which consists of three exons encoding 813 bp. cDNA analysis from hair follicles revealed the expression of two FGF5 alternative spliced transcripts, in one of which exon 2 is absent. DNA variation analysis showed four polymorphisms in the coding region: a synonymous SNP (c.210A>G), a single base deletion (c.348delA), a 12-bp insertion (c.351_352insCATATAACATAG) and a non-sense mutation (c.499C>T). The deletion was always found together with the insertion forming a haplotype and producing a putative truncated protein of 123 amino acids. The c.499C>T mutation also leads to a premature stop codon at position 168. In both cases, critical functional domains of FGF5, including one heparin binding site, are lost. All animals analyzed were homozygous for one of the deleterious mutations or compound heterozygous for both (i.e. c.348delA, c.351_352insCATATAACATAG/c.499T). Sequencing of guanaco samples showed that the FGF5 gene encodes a full-length 270-amino acid protein. These results suggest that FGF5 is likely functional in short-haired wild species and non-functional in the domestic fiber-producing species, the llama.

Cdrom Archive: A Gateway to Study Camel Phenotypes

“…Fibroblast growth factor-5 ( FGF5 ) has been identified to be associated with, or responsible for, long hair in many mammals, including llamas (Daverio et al, 2017), alpacas (Pallotti et al, 2018), donkeys (Legrand et al, 2014), sheep (Zhang et al, 2015), goats (Wang et al, 2016), cats (Drögemüller et al, 2007), dogs (Dierks et al, 2013), rabbits (Mulsant et al, 2010), mice (Hébert et al, 1994), and humans (Higgins et al, 2014). It is thus justifiable to consider FGF5 as a strong candidate gene for long hair in Mezayen camels, and this hypothesis can be investigated via direct sequencing.…”

A nonsense mutation in the FGF5 gene is associated with the long‐haired phenotype in domestic guinea pigs (Cavia porcellus)

“…This mutation was genotyped by direct sequencing analysis in 141 short‐haired and 70 long‐haired individuals. We found 104 homozygous CC and 37 heterozygous CT short‐haired individuals, whereas all long‐haired individuals were homozygous TT, indicating that the long‐haired phenotype is inherited as a recessive trait as in other mammalian species …”

“…In mammals, the disruption of hair growth regulation can result in abnormal hair morphogenesis. Mutations in the FGF5 gene encoding fibroblast growth factor 5, which plays an important role in inducing catagen, have been associated with long‐haired phenotypes in Syrian hamsters, dogs, cats, donkeys and llamas . Domestic guinea pigs ( Cavia porcellus ) with long hair are very popular as pets in many countries because of their appealing appearance (Fig.…”

FGF5 missense mutation is associated with dromedary hair length variation

“…At position p.67, alpacas and llamas have two alleles (C/T), which affect the corresponding amino acid where the (C) allele codes for arginine and the (T) allele causes a pre‐mature stop codon (Daverio et␣al . 2017; Pallotti et␣al . 2018).…”