The untranslated side of hair and skin mammalian pigmentation: Beyond coding sequences

Abstract

SummaryFor several decades, tremendous advances in studying skin and hair pigmentation of mammals have been made using Mendelian genetics principles. A number of loci and their associated traits have been extensively examined, crossings performed, and phenotypes well documented. Continuously improving PCR techniques allowed the molecular cloning and sequencing of the first pigmentation genes at the end of the 20th century, a period followed by an intense effort to detect and describe polymorphisms in the coding regions and correlate allelic combinations with the observed melanogenic phenotypes. However, a number of phenotypes and biological events could not be elucidated solely by analysis of the coding regions of genes. Messenger RNA isolation, characterization and quantification techniques allowed groups to move ahead and investigate molecular mechanisms whose secrets lay within the noncoding regions of pigmentation genes transcripts such as MC1R, ASIP, or Mitf. The untranslated elements contain specific nucleotidic sequences and structures that dramatically influence the mRNA half-life and processing thus impacting protein translation and melanin production. As we are progressively uncovering the complex processes regulating melanocyte biology, unraveling complete mRNA structures and understanding mechanisms beyond coding regions has become critical. IUBMBIUBMB Life, 62(5): [340][341][342][343][344][345][346] 2010

Regulatory pathway analysis of coat color genes in Mongolian horses

“…The interactions of several basic factors, most of which are from single genetic loci, are responsible for the various colors of most horses. With the development of advanced sequencing technology, skin and coat color genetics have been well studied [ 10 ]; however, most studies have focused on gene polymorphisms, whereas the impact of gene expression on coat color has not been well characterized.…”

Single-nucleotide polymorphism of MC1R, ASIP, and TYRP2 genes in wild and farmed foxes (Vulpes vulpes)

“…Another example is the phenotype of the silver fox from Alaska, which is an example of an MC1R mutation (Cys-Arg at position 125; C125R), and interestingly, the phenotype of the standard silver fox is caused by a deletion in the locus agouti. In addition, changes in pigmentation in sheep are associated with both single mutations in MC1R and duplications in the ASIP (Rouzaud et al 2010), suggesting that the gene interaction between MC1R and ASIP in this case may be responsible for the red coat in individuals from Alaska (Klungland and Vage 2003).…”

“…This results in a change in the amount of melanin synthesis, accumulation of eumelanin, and a change in color to red/yellow (Dessinioti et al 2011). It has been demonstrated that single mutations in the MC1R exon are also linked to changes in pigmentation in many animal species (mice, cattle, horses, pigs, and dogs) (Rouzaud et al 2010). A number of researches have shown that the variant of the MC1R gene has a significant influence on phenotype (Brudnik et al 2006).…”

Estudio molecular de genes candidatos para el color de capa de llamas (<i>Lama glama</i>)

“…Las 5'UTR son importantes regiones regulatorias ya que controlan la expresión de los genes a través de distintos elementos presentes en su secuencia: sitios internos de entrada de ribosomas (IRES), sitios de unión a proteínas represoras o activadoras, estructura secundaria de la región, codones de inicio no AUGs, entorno del AUG, codones de inicio previos al marco de lectura (uAUG) y marcos de lectura previos al principal (uORF) (Barbosa et al, 2013). La variación que presentan las 5'UTRs es igual o incluso de mayor importancia que la variación en regiones codificantes para la determinación del fenotipo (Rouzaud et al, 2010). En ASIP, particularmente, existen varios estudios en animales domésticos y silvestres que relacionan transcriptos con diferentes 5´UTRs con colores y patrones de pigmentación.…”