Deformities in cultured fish species may be genetic, and identifying causative genes is essential to expand production and maintain farmed animal welfare. We previously reported a genetic deformity in juvenile red sea bream, designated a transparent phenotype. To identify its causative gene, we conducted genome-wide linkage analysis and identified two single nucleotide polymorphisms (SNP) located on LG23 directly linked to the transparent phenotype. The scaffold on which the two SNPs were located contained two candidate genes, duox and duoxa, which are related to thyroid hormone synthesis. Four missense mutations were found in duox and one in duoxa, with that in duoxa showing perfect association with the transparent phenotype. The mutation of duoxa was suggested to affect the transmembrane structure and thyroid-related traits, including an enlarged thyroid gland and immature erythrocytes, and lower thyroxine (T₄) concentrations were observed in the transparent phenotype. The transparent phenotype was rescued by T₄ immersion. Loss-of-function of duoxa by CRISPR–Cas9 induced the transparent phenotype in zebrafish. Evidence suggests that the transparent phenotype of juvenile red sea bream is caused by the missense mutation of duoxa and that this mutation disrupts thyroid hormone synthesis. The newly identified missense mutation will contribute to effective selective breeding of red sea bream to purge the causative gene of the undesirable phenotype and improve seed production of red sea bream as well as provide basic information of the mechanisms of thyroid hormones and its related diseases in fish and humans.

养殖鱼类的畸形可能是遗传性的，识别致病基因对于扩大生产和维持养殖动物福利至关重要。我们之前报道了幼年红海鲷的遗传畸形，指定为透明表型。为了鉴定其致病基因，我们进行了全基因组连锁分析，并鉴定了位于 LG23 上的两个单核苷酸多态性 (SNP)，与透明表型直接相关。两个 SNP 所在的支架包含两个候选基因duox和duoxa，它们与甲状腺激素合成有关。在duox中发现了4个错义突变，在duoxa中发现了1个错义突变，其中duoxa中发现了错义突变。显示与透明表型的完美关联。提示duoxa的突变影响跨膜结构和甲状腺相关性状，包括增大的甲状腺和未成熟的红细胞，并且在透明表型中观察到较低的甲状腺素（T _{4 ）浓度。}通过 T ₄浸泡挽救了透明表型。CRISPR-Cas9 对duoxa的功能丧失诱导了斑马鱼的透明表型。有证据表明，真鲷幼鱼的透明表型是由duoxa的错义突变引起的并且这种突变会破坏甲状腺激素的合成。新发现的错义突变将有助于红海鲷的有效选育，清除不良表型的致病基因，提高红海鲷的种子产量，并为鱼类甲状腺激素及其相关疾病的机制提供基本信息。和人类。