The genome sequencing of an albino Western lowland gorilla reveals inbreeding in the wild

Abstract

Background: The only known albino gorilla, named Snowflake, was a male wild born individual from Equatorial Guinea who lived at the Barcelona Zoo for almost 40 years. He was diagnosed with non-syndromic oculocutaneous albinism, i.e. white hair, light eyes, pink skin, photophobia and reduced visual acuity. Despite previous efforts to explain the genetic cause, this is still unknown. Here, we study the genetic cause of his albinism and making use of whole genome sequencing data we find a higher inbreeding coefficient compared to other gorillas.

Results: We successfully identified the causal genetic variant for Snowflake's albinism, a non-synonymous single nucleotide variant located in a transmembrane region of SLC45A2. This transporter is known to be involved in oculocutaneous albinism type 4 (OCA4) in humans. We provide experimental evidence that shows that this amino acid replacement alters the membrane spanning capability of this transmembrane region. Finally, we provide a comprehensive study of genome-wide patterns of autozygogosity revealing that Snowflake's parents were related, being this the first report of inbreeding in a wild born Western lowland gorilla.

Conclusions: In this study we demonstrate how the use of whole genome sequencing can be extended to link genotype and phenotype in non-model organisms and it can be a powerful tool in conservation genetics (e.g., inbreeding and genetic diversity) with the expected decrease in sequencing cost.

Figure 1

Snowflake, the only known albino gorilla. This Western lowland gorilla was wild-born in Equatorial Guinea and he presented the typical characteristics of oculocutaneous albinism.

Figure 2

Membrane integration of non-albino wild-type (wt) and mutant (Snowflake) G518R sequences. (a) Schematic representation of the engineered leader peptidase (Lep) model protein. Wild-type Lep has two transmembrane (TM) helices (H1 and H2) and a large C-terminal luminal domain (P2). It inserts into rough microsomal (RM) membranes in an Nt/Ct ER luminal orientation. SLC45A2 TM12 domains (TM12) wild-type and G518R mutant were inserted in the P2 domain flanked by two glycosylation acceptor sites (G1 and G2). If the inserted sequence integrates into the membrane, only the G1 site is glycosylated (left), whereas both G1 and G2 sites are glycosylated for the sequences that do not integrate into the membrane (right). (b) Plasmids encoding the constructs were transcribed and translated in vitro in the absence (−) and presence (+) of RM membranes. Non-glycosylated protein bands are indicated by a white dot; singly or doubly glycosylated proteins are indicated by one or two black dots, respectively. (c) SLC45A2 TM12 sequence in each construct and ΔG_app values predicted using the ΔG Prediction Server (http://dgpred.cbr.su.se/) and deduced from the data in panel b are shown.

Figure 3

Heterozygosity distributions of the studied gorillas. (a) Heterozygosity values in 1 Mbp non-overlapping windows along the human chromosome 5. The SLC45A2 gene is contained within a 40 Mbp run of homozygosity in Snowflake (blue). The other two gorillas do not show any run of homozygosity (Kamilah in red and Kwan in green). (b) Distribution of the heterozygosity values of 1Mbp non-overlapping windows in the aforementioned gorillas. While most of the genome shows a similar distribution, we observe an excess of windows with less heterozygosity as a result of the inbreeding observed in Snowflake.