Institut de Biologia Evolutiva, (CSIC-Universitat Pompeu Fabra), PRBB, Barcelona 08003, Spain.
BMC Genomics. 2013 May 31;14:363. doi: 10.1186/1471-2164-14-363.
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.
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.
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.
已知的白化大猩猩唯一一只，名为“雪花”，是一只来自赤道几内亚的野生雄性个体，在巴塞罗那动物园生活了近 40 年。他被诊断患有非综合征性眼皮肤白化病，即白头发、浅色眼睛、粉红色皮肤、畏光和视力下降。尽管此前曾努力解释其遗传原因，但这仍然未知。在这里，我们研究了他白化病的遗传原因，并利用全基因组测序数据发现，与其他大猩猩相比，它的近交系数更高。
我们成功确定了雪花白化病的致病遗传变异，这是一个位于 SLC45A2 跨膜区域的非同义单核苷酸变异。该转运蛋白已知与人类的眼皮肤白化病 4 型（OCA4）有关。我们提供了实验证据表明，这种氨基酸替换改变了这个跨膜区域的膜贯穿能力。最后，我们对全基因组自交模式进行了全面研究，揭示雪花的父母是有亲缘关系的，这是首次报道野生出生的西部低地大猩猩存在近亲繁殖。
在这项研究中，我们展示了如何将全基因组测序的应用扩展到非模式生物中的基因型和表型之间的联系，并且它可以成为保护遗传学（例如近亲繁殖和遗传多样性）的有力工具，预计测序成本会降低。
