Identification of Genetic Mutations in TYR and OCA2 Genes in Congenital Families with Oculocutaneous Albinism (OCA)

Aim: The objective of the present study was to recruit congenital families of oculocutaneous albinism (OCA) and mutations in TYR and OCA2 genes are identified, which is further expanding the mutation spectrum in this population. Methods: Two consanguineous families with OCA were recruited and whole blood was collected. Clinical examination was carried out to determine the visual acuity and related eye, skin and hair examinations. Genomic DNA was extracted by standard phenol-chloroform method. Targeted exome sequencing by TruSight one sequencing panel sequencing was carried out. Sanger sequencing was performed for mutation detection in tyrosinase (TYR) and the OCA2 genes and co-segregation in OCA families. Results: Clinically, the affected individuals of two OCA families showed clinical characteristics including white to pale skin, white or blonde hairs, irritant to light, nystagmus and reduced vision. DNA sequencing showed the genetic mutation of TYR and OCA2 genes in two OCA families. In family 1, the nucleotide variant (c.1255G>A; p.Gly419Arg) was detected inTYR gene, while in another family, the splice-site variant c.1045-15T>G was identified in OCA2. Conclusion: This study concluded that identification of TYR and OCA2 mutations in OCA disease are commonly associated with the population where the consanguinity is persistent. These findings expanded the molecular basis of oculocutaneous albinism in Pakistani families and established the mode of genetic counselling and for diagnostic outcome. Keywords: Consanguineous families; Oculocutaneous albinism (OCA); mutations; tyrosinase (TYR); OCA2 gene.

Pleiotropic function of the oca2 gene underlies the evolution of sleep loss and albinism in cavefish

SummaryAdaptation to novel environments often involves the evolution of multiple morphological, physiological and behavioral traits. One striking example of multi-trait evolution is the suite of traits that has evolved repeatedly in cave animals, including regression of eyes, loss of pigmentation, and enhancement of non-visual sensory systems [1,3]. The Mexican tetra, Astyanax mexicanus, consists of fish that inhabit at least 30 caves in Northeast Mexico and ancestral-like surface fish which inhabit the rivers of Mexico and Southern Texas [6]. Cave A. mexicanus are interfertile with surface fish and have evolved a number of traits that are common to cave animals throughout the world, including albinism, eye loss, and alterations to behavior [8–10]. To define relationships between different cave-evolved traits, we phenotyped 208 surface-cave F2 hybrid fish for numerous morphological and behavioral traits. We found significant differences in sleep between pigmented and albino hybrid fish, raising the possibility that these traits share a genetic basis. In cavefish and many other species, mutations in oculocutaneous albinism 2 (oca2) cause albinism [11–15]. Surface fish with CRISPR-induced mutations in oca2 displayed both albinism and reduced sleep. Further, this mutation in oca2 fails to complement sleep loss when surface fish harboring this engineered mutation are crossed to different, independently evolved populations of albino cavefish with naturally occurring mutations in oca2, confirming that oca2 contributes to sleep loss. Finally, analysis of the oca2 locus in wild caught cave and surface fish suggests that oca2 is under positive selection in at least three cave populations. Taken together, these findings identify oca2 as a novel regulator of sleep and suggest that a pleiotropic function of oca2 underlies the adaptive evolution of both of albinism and sleep loss.

The distinctive geographic patterns of common pigmentation variants at the OCA2 gene

Oculocutaneous Albinism type 2 (OCA2) is a gene of great interest because of genetic variation affecting normal pigmentation variation in humans. The diverse geographic patterns for variant frequencies at OCA2 have been evident but have not been systematically investigated, especially outside of Europe. Here we examine population genetic variation in and near the OCA2 gene from a worldwide perspective. The very different patterns of genetic variation found across world regions suggest strong selection effects may have been at work over time. For example, analyses involving the variants that affect pigmentation of the iris argue that the derived allele of the rs1800407 single nucleotide polymorphism, which produces a hypomorphic protein, may have contributed to the previously demonstrated positive selection in Europe for the enhancer variant responsible for light eye color. More study is needed on the relationships of the genetic variation at OCA2 to variation in pigmentation in areas beyond Europe.