Alternative titles; symbols
HGNC Approved Gene Symbol: DNALI1
Cytogenetic location: 1p34.3 Genomic coordinates (GRCh38): 1:37,556,940-37,566,857 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1p34.3 | ?Spermatogenic failure 83 | 620354 | Autosomal recessive | 3 |
The DNALI1 gene encodes a subunit of the light intermediate chain of inner dynein arms of the axoneme of sperm flagella (summary by Wu et al., 2023).
Kastury et al. (1997) cloned the full-length human axonemal dynein light-chain cDNA, a homolog of the Chlamydomonas inner dynein arm gene p28. The human p28 gene is encoded by a 921-bp transcript with an open reading frame of 257 amino acids. Northern blot analysis revealed 2 human p28 transcripts of 0.9 and 2.5 kb in many tissues. The 0.9-kb transcript is expressed at a 20-fold higher level than the 2.5-kb transcript in the testis.
Wu et al. (2023) analyzed Dnali1 expression during spermatogenesis in mice. Dnali1 was detected in the cytoplasm during spermiogenesis, with strong signals detected in spermatocytes from mid-pachytene to metaphase II. Immunofluorescence staining of testicular single-cell suspensions showed expression of Dnali1 in the cytoplasm of round spermatids prior to flagellar formation. The authors noted that there were no Dnali1 signals on the flagella at the initial protrusion from the cytoplasm, but Dnali1 was reassembled after that process, suggesting that DNALI1 may possess other functions in addition to being a component of the inner dynein arms.
Using somatic cell and radiation hybrid panels, Kastury et al. (1997) mapped the p28 gene to human chromosome 1p35.1.
Stumpf (2023) mapped the DNALI1 gene to chromosome 1p34.3 based on an alignment of the DNALI1 sequence (GenBank AK290502) with the genomic sequence (GRCh38).
In a Chinese man with infertility due to asthenozoospermia (SPGF83; 620354), Wu et al. (2023) identified homozygosity for a 4-bp deletion in the DNALI1 gene (602135.0001). The mutation segregated with disease in the family and was not found in public variant databases. Patient sperm were completely immotile, and DNALI1 was not detected in patient sperm samples.
Wu et al. (2023) generated Dnali1 -/- mice and observed that although the morphology of their spermatozoa appeared completely normal, all epididymal sperm were immotile. Transmission electron microscopy showed fibrous sheath abnormalities in a majority of sperm. In addition, analysis of mutant flagella revealed that AKAP3 (604689) and AKAP4 (300185), important structural proteins of the fibrous sheath, were asymmetrically distributed and significantly reduced, respectively. DNAH1 (603332) and DNAH7 (610061) signals were absent from mutant flagella.
In a Chinese man (AC050) with infertility due to asthenozoospermia (SPGF83; 620354), Wu et al. (2023) identified homozygosity for a 4-bp deletion (c.663_666del, NM_003462.5) in the DNALI1 gene, causing a frameshift predicted to result in a premature termination codon (Glu221fsTer). Sanger sequencing confirmed the deletion and its presence in heterozygosity in his unaffected consanguineous parents. The deletion was not found in the 1000 Genomes Project, ExAC, or gnomAD databases. Immunoblotting and immunostaining showed that DNALI1 was completely absent from patient sperm samples. In addition, patient sperm lacked DNAH1 (603332) and DNAH7 (610061).
Kastury, K., Taylor, W. E., Shen, R., Arver, S., Gutierrez, M., Fisher, C. E., Coucke, P. J., Van Hauwe, P., Van Camp, G., Bhasin, S. Complementary deoxyribonucleic acid cloning and characterization of a putative human axonemal dynein light chain gene. J. Clin. Endocr. Metab. 82: 3047-3053, 1997. [PubMed: 9284741] [Full Text: https://doi.org/10.1210/jcem.82.9.4242]
Stumpf, A. M. Personal Communication. Baltimore, Md. 04/27/2023.
Wu, H., Liu, Y., Li, Y., Li, K., Xu, C., Gao, Y., Lv, M., Guo, R., Xu, Y., Zhou, P., Wei, Z., Hua, R., He, X., Cao, Y. DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath. Cell Death Dis. 14: 127, 2023. [PubMed: 36792588] [Full Text: https://doi.org/10.1038/s41419-023-05653-y]