Dthd1, whose specific function and associated pathways are yet to be fully characterized, has been emerging as a gene of interest in multiple biological contexts. Its study through genetic models could potentially shed light on its essential roles in various biological processes.

In systemic lupus erythematosus (SLE), a mutation of DTHD1 was found to be closely correlated with the abnormal accumulation of CD161-CD8+ TEMRA cells. DTHD1 interacts with MYD88 to suppress its activity in T cells, and its mutation promotes the MYD88-dependent pathway, increasing the proliferation and cytotoxicity of CD161-CD8+ TEMRA cells, which are critical for SLE pathogenesis [1]. In Alzheimer's disease, DTHD1 was identified as one of the 9 up-regulated differentially expressed genes, indicating its potential involvement in the disease [2]. In glioblastoma, DTHD1 was among the five molecules identified through PCR validation and clinical data mining, suggesting its possible role in N6-methyladenosine-mediated GBM development [3]. In Chinese Holstein cows, DTHD1 was selected as a candidate gene that might affect Loin Strength, a reproduction-related body-shape trait [4]. In liver cancer, DTHD1 was one of the top differentially expressed genes in hepatocellular carcinoma (HCC), potentially serving as a biomarker and a target for therapeutic strategies [5]. Also, in hepatocellular carcinoma, overexpression of miR-3131 led to a significant decrease in DTHD1 mRNA level, suggesting its role in the carcinogenesis of HCC [6]. DTHD1 was also identified as a novel candidate disease gene in retinal dystrophy, and a 4p homozygous microdeletion encompassing DTHD1 was found in a dysmorphic girl with CYP1B1-negative primary congenital glaucoma, suggesting its potential association with the disease [7,8].

In summary, Dthd1 appears to be involved in multiple biological processes and diseases, including autoimmune diseases, neurodegenerative diseases, cancers, and hereditary eye diseases. Although the exact mechanisms of its functions are still being explored, research on Dthd1 using genetic models could contribute to understanding the pathogenesis of these diseases and potentially lead to new diagnostic and treatment strategies.

References:

1. Xiong, Hui, Cui, Mintian, Kong, Ni, Guo, Qing, Chen, Kun. 2023. Cytotoxic CD161-CD8+ TEMRA cells contribute to the pathogenesis of systemic lupus erythematosus. In EBioMedicine, 90, 104507. doi:10.1016/j.ebiom.2023.104507. https://pubmed.ncbi.nlm.nih.gov/36893588/

2. Lamisa, Anika Bushra, Ahammad, Ishtiaque, Bhattacharjee, Arittra, Salimullah, Md, Keya, Chaman Ara. 2024. A meta-analysis of bulk RNA-seq datasets identifies potential biomarkers and repurposable therapeutics against Alzheimer's disease. In Scientific reports, 14, 24717. doi:10.1038/s41598-024-75431-z. https://pubmed.ncbi.nlm.nih.gov/39433822/

3. Zhang, Yuhao, Geng, Xiuchao, Xu, Jianglong, Fang, Chuan, Wang, Hong. 2021. Identification and characterization of N6-methyladenosine modification of circRNAs in glioblastoma. In Journal of cellular and molecular medicine, 25, 7204-7217. doi:10.1111/jcmm.16750. https://pubmed.ncbi.nlm.nih.gov/34180136/

4. Lu, Xubin, Abdalla, Ismail Mohamed, Nazar, Mudasir, Xu, Tianle, Yang, Zhangping. 2021. Genome-Wide Association Study on Reproduction-Related Body-Shape Traits of Chinese Holstein Cows. In Animals : an open access journal from MDPI, 11, . doi:10.3390/ani11071927. https://pubmed.ncbi.nlm.nih.gov/34203505/

5. Swain, Asish Kumar, Pandey, Prashant, Sera, Riddhi, Yadav, Pankaj. 2023. Single-cell transcriptome analysis identifies novel biomarkers involved in major liver cancer subtypes. In Functional & integrative genomics, 23, 235. doi:10.1007/s10142-023-01156-3. https://pubmed.ncbi.nlm.nih.gov/37438675/

6. Wang, Chaoqun, Li, Lijuan, Yin, Zhixia, Zhu, Shaohua, Gao, Yuzhen. . An indel polymorphism within pre-miR3131 confers risk for hepatocellular carcinoma. In Carcinogenesis, 38, 168-176. doi:10.1093/carcin/bgw206. https://pubmed.ncbi.nlm.nih.gov/28034876/

7. Abu-Safieh, Leen, Alrashed, May, Anazi, Shamsa, Al-Hazzaa, Selwa A F, Alkuraya, Fowzan S. 2012. Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. In Genome research, 23, 236-47. doi:10.1101/gr.144105.112. https://pubmed.ncbi.nlm.nih.gov/23105016/

8. Abu-Amero, Khaled K, Kondkar, Altaf A, Khan, Arif O. 2014. Molecular Karyotyping of a Dysmorphic Girl from Saudi Arabia with CYP1B1-negative Primary Congenital Glaucoma. In Ophthalmic genetics, 37, 98-101. doi:10.3109/13816810.2014.924017. https://pubmed.ncbi.nlm.nih.gov/24911043/