DNAI1 explained

Dynein axonemal intermediate chain 1 is a protein that in humans is encoded by the DNAI1 gene.^{[1] [2]}

The inner- and outer-arm dyneins, which bridge between the doublet microtubules in axonemes, are the force-generating proteins responsible for the sliding movement in axonemes. The intermediate and light chains, thought to form the base of the dynein arm, help mediate attachment and may also participate in regulating dynein activity. This gene encodes an intermediate chain dynein, belonging to the large family of motor proteins. Mutations in this gene result in abnormal ciliary ultrastructure and function associated with primary ciliary dyskinesia (PCD) and Kartagener syndrome. The DNAI1 gene is involved in the development of proper respiratory function, motility of spermatozoa, and asymmetrical organization of the viscera during embryogenesis. This gene affects these three very different aspects of development because all three are dependent on proper cilia function. DNAI1 codes for the development of cilia ultrastructure in the upper and lower respiratory tracts, spermatozoa flagellae, and nodal cilia (cilia of the primitive node). DNAI1 specifically encodes for an intermediate chain of the outer dynein arm. Each dynein arm of the ciliary axoneme has an inner and outer dynein arm. A mutation in DNAI1 can lead to defective ciliary beating. A DNAI1 gene mutation accounts for 4-10% of all cases of primary ciliary dyskensia (PCD). The most frequent structural defect in cilia of PCD patients are abnormal dynein arms. A common mutation of DNAI1 leading to PCD is a hot-spot mutation in intron 1 of the gene. Mutations in coding or splicing are only found in 10% of PCD cases.^[2]

External links

• GeneReviews/NIH/NCBI/UW entry on Primary Ciliary Dyskinesia

Further reading

• Guichard C, Harricane MC, Lafitte JJ . Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome) . American Journal of Human Genetics . 68 . 4 . 1030–1035 . 2001 . 11231901 . 10.1086/319511 . 1275621 . etal.
• Zariwala M, Noone PG, Sannuti A . Germline mutations in an intermediate chain dynein cause primary ciliary dyskinesia . American Journal of Respiratory Cell and Molecular Biology . 25 . 5 . 577–583 . 2002 . 11713099 . 10.1165/ajrcmb.25.5.4619. 38096706 . etal.
• Tai CY, Dujardin DL, Faulkner NE, Vallee RB . Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function . Journal of Cell Biology . 156 . 6 . 959–968 . 2002 . 11889140 . 10.1083/jcb.200109046 . 2173479 .
• Noone PG, Zariwala M, Sannuti A . Mutations in DNAI1 (IC78) cause primary ciliary dyskinesia . Chest . 121 . 3 Suppl . 97S . 2002 . 11893720 . 10.1378/chest.121.3_suppl.97S . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proceedings of the National Academy of Sciences of the United States of America . 99 . 26 . 16899–16903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Ficarro S, Chertihin O, Westbrook VA . Phosphoproteome analysis of capacitated human sperm — Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation . Journal of Biological Chemistry . 278 . 13 . 11579–89 . 2003 . 12509440 . 10.1074/jbc.M202325200 . etal. free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nature Genetics . 36 . 1 . 40–45 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Humphray SJ, Oliver K, Hunt AR . DNA sequence and analysis of human chromosome 9 . Nature . 429 . 6990 . 369–374 . 2004 . 15164053 . 10.1038/nature02465 . 2734081 . 2004Natur.429..369H . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Research . 14 . 10B . 2121–2127 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Zariwala MA, Leigh MW, Ceppa F . Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation . American Journal of Respiratory and Critical Care Medicine . 174 . 8 . 858–866 . 2006 . 16858015 . 10.1164/rccm.200603-370OC . 2648054 . etal.

Notes and References

1. Pennarun G, Escudier E, Chapelin C, Bridoux AM, Cacheux V, Roger G, Clement A, Goossens M, Amselem S, Duriez B . Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia . American Journal of Human Genetics . 65 . 6 . 1508–19 . Jan 2000 . 10577904 . 1288361 . 10.1086/302683 .
2. Web site: Entrez Gene: DNAI1 dynein, axonemal, intermediate chain 1.