Identification of the causative gene of a transparent phenotype of juvenile red sea bream Pagrus major
Identification of the causative gene of a transparent phenotype of juvenile red sea bream Pagrus major
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DOI：
10.1038/s41437-021-00448-3
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发表时间：
2021-06
期刊：
影响因子：
3.8
通讯作者：
E. Sawayama;Y. Handa;Koichiro Nakano;D. Noguchi;M. Takagi;Yosuke Akiba;Shuwa Sanada;G. Yoshizaki;Hayato Usui;Kenta Kawamoto;Miwa Suzuki;K. Asahina
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文献类型：
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作者：
E. Sawayama;Y. Handa;Koichiro Nakano;D. Noguchi;M. Takagi;Yosuke Akiba;Shuwa Sanada;G. Yoshizaki;Hayato Usui;Kenta Kawamoto;Miwa Suzuki;K. Asahina
养殖鱼类的畸形可能是遗传性的，识别致病基因对扩大产量和维护养殖动物福利至关重要。我们以前曾报道过一种遗传畸形的少年红鲷，指定一个透明的表型。为了确定其致病基因，我们进行了全基因组连锁分析，并确定了两个单核苷酸多态性（SNP）位于LG 23直接链接到透明表型。两个SNP所在的支架包含两个候选基因duoxandduoxa，它们与甲状腺激素合成有关。发现了4个错义突变induox和1个induoxa，induoxa与透明表型完全相关。duoxa基因突变可能影响甲状腺的跨膜结构和甲状腺相关性状，包括甲状腺增大和红细胞不成熟，透明表型中甲状腺素（T4）浓度降低。透明表型通过T4浸泡被拯救。duoxaby CRISPR-Cas9的功能丧失诱导了斑马鱼的透明表型。有证据表明，幼真鲷的透明表型是由duoxa的错义突变引起的，这种突变破坏了甲状腺激素的合成。新发现的错义突变将有助于真鲷的有效选择育种，以清除不良表型的致病基因，提高真鲷的种子产量，并为鱼类和人类甲状腺激素及其相关疾病的机制提供基础信息。
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,duoxandduoxa, which are related to thyroid hormone synthesis. Four missense mutations were found induoxand one induoxa, with that induoxashowing perfect association with the transparent phenotype. The mutation ofduoxawas 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 T4immersion. Loss-of-function ofduoxaby 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 ofduoxaand 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.