Data from: A missense mutation in SLC45A2 is associated with albinism in several small long haired dog breeds

Homozygosity for a large deletion in the solute carrier family 45, member
2 (SLC45A2) gene causes oculocutaneous albinism (OCA) in the Doberman
Pinscher breed. An albino Lhasa Apso did not have this g.27141_31223del
(CanFam2) deletion in her SLC45A2 sequence. Therefore, SLC45A2 was
investigated in this female Lhasa Apso to search for other possible
variants that caused her albinism. The albino Lhasa Apso was homozygous
for a nonsynonymous substitution in the seventh exon, a c.1478G>A
base change that resulted in a glycine to aspartic acid substitution
(p.G493D). This mutation was not found in a wolf, a coyote, or any of the
15 other Lhasa Apso dogs or 32 other dogs of breeds related to the Lhasa
Apso. However, an albino Pekingese, 2 albino Pomeranians, and an albino
mixed breed dog that was small and long haired were also homozygous for
the 493D allele. The colored puppies of the albino Lhasa Apso and the
colored dam of the 2 albino Pomeranians were heterozygous for this allele.
However, an albino Pug was homozygous for the 493G allele and therefore
although we suggest the 493D allele causes albinism when homozygous in
several small, long haired dog breeds, it does not explain all albinism in
dogs. A variant effect prediction for the albino Lhasa Apso confirms that
p.G493D is a deleterious substitution, and a topology prediction for
SLC45A2 suggests that the 11th transmembrane domain where the 493rd amino
acid was located, has an altered structure.

溶质转运蛋白家族45成员2（solute carrier family 45 member 2，SLC45A2）基因大片段纯合缺失，可导致杜宾犬（Doberman Pinscher）发生眼皮肤白化病（oculocutaneous albinism，OCA）。一只白化拉萨犬的SLC45A2序列中，并未携带该g.27141_31223del（CanFam2）缺失变异。因此，研究人员针对这只雌性白化拉萨犬的SLC45A2基因展开探究，以寻找可能导致其白化表型的其他遗传变异。该白化拉萨犬在第7外显子存在一处错义突变：c.1478G>A碱基替换，该变异会导致编码蛋白的第493位氨基酸由甘氨酸突变为天冬氨酸（p.G493D）。对1只狼、1只郊狼、15只其他拉萨犬以及32只与拉萨犬亲缘关系较近的其他品种犬进行检测，均未发现该突变。不过，1只白化北京犬、2只白化博美犬，以及1只小型长毛混血白化犬，均为该493D等位基因的纯合携带者。该白化拉萨犬与两只白化博美犬的有色母犬所产的有色幼犬，均为该等位基因的杂合携带者。但1只白化巴哥犬为493G等位基因的纯合携带者。由此可见，尽管我们推测493D等位基因在多个小型长毛犬品种中纯合时可引发白化病，但该变异并不能解释所有犬类白化病例。针对该白化拉萨犬的变异效应预测结果证实，p.G493D属于有害错义突变；而SLC45A2蛋白的拓扑结构预测显示，第493位氨基酸所在的第11个跨膜结构域（transmembrane domain）的结构发生了改变。