AHI1 explained

The Abelson helper integration site 1 (AHI1) is a protein coding gene that is known for the critical role it plays in brain development.^[1] Proper cerebellar and cortical development in the human brain depends heavily on AHI1. The AHI1 gene is prominently expressed in the embryonic hindbrain and forebrain. AHI1 specifically encodes the Jouberin protein and mutations in the expression of the gene is known to cause specific forms of Joubert syndrome. Joubert syndrome is autosomal recessive and is characterized by the brain malformations and mental retardation that AHI1 mutations have the potential to induce.^[2] AHI1 has also been associated with schizophrenia and autism due to the role it plays in brain development.^[3] An AHI1 heterozygous knockout mouse model was studied by Bernard Lerer and his group at Hadassah Medical Center in Jerusalem to elucidate the correlation between alterations in AHI1 expression and the pathogenesis of neuropsychiatric disorders. The core temperatures and corticosterone secretions of the heterozygous knockout mice after exposure to environmental and visceral stress exhibited extreme repression of autonomic nervous system and hypothalamic-pituitary-adrenal responses. The knockout mice demonstrated an increased resilience to different types of stress and these results lead to a correlation between emotional regulation and neuropsychiatric disorders.

Jouberin is a protein that in humans is encoded by the AHI1 gene.^{[4] [5] [6]}

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.
• Hartley JL, Temple GF, Brasch MA . DNA Cloning Using In Vitro Site-Specific Recombination . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Wiemann S, Weil B, Wellenreuther R . Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 10.1101/gr.GR1547R . 311072 . etal.
• Jiang X, Hanna Z, Kaouass M . Ahi-1, a Novel Gene Encoding a Modular Protein with WD40-Repeat and SH3 Domains, Is Targeted by the Ahi-1 and Mis-2 Provirus Integrations . J. Virol. . 76 . 18 . 9046–59 . 2002 . 12186888 . 10.1128/JVI.76.18.9046-9059.2002 . 136442 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Mungall AJ, Palmer SA, Sims SK . The DNA sequence and analysis of human chromosome 6 . Nature . 425 . 6960 . 805–11 . 2003 . 14574404 . 10.1038/nature02055 . 2003Natur.425..805M . etal. free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Jiang X, Zhao Y, Chan WY . Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia . Blood . 103 . 10 . 3897–904 . 2004 . 14751929 . 10.1182/blood-2003-11-4026 . etal. free .
• Close J, Game L, Clark B . Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults . BMC Genomics . 5 . 1 . 33 . 2004 . 15169551 . 10.1186/1471-2164-5-33 . 441375 . etal . free .
• Ferland RJ, Eyaid W, Collura RV . Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome . Nat. Genet. . 36 . 9 . 1008–13 . 2004 . 15322546 . 10.1038/ng1419 . etal. free .
• Dixon-Salazar T, Silhavy JL, Marsh SE . Mutations in the AHI1 Gene, Encoding Jouberin, Cause Joubert Syndrome with Cortical Polymicrogyria . Am. J. Hum. Genet. . 75 . 6 . 979–87 . 2005 . 15467982 . 10.1086/425985 . 1182159 . 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 Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Wiemann S, Arlt D, Huber W . From ORFeome to Biology: A Functional Genomics Pipeline . Genome Res. . 14 . 10B . 2136–44 . 2004 . 15489336 . 10.1101/gr.2576704 . 528930 . etal.
• Parisi MA, Doherty D, Eckert ML . AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome . J. Med. Genet. . 43 . 4 . 334–9 . 2006 . 16155189 . 10.1136/jmg.2005.036608 . 2563230 . etal.
• Mehrle A, Rosenfelder H, Schupp I . The LIFEdb database in 2006 . Nucleic Acids Res. . 34 . Database issue . D415–8 . 2006 . 16381901 . 10.1093/nar/gkj139 . 1347501 . etal.
• Valente EM, Brancati F, Silhavy JL . AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders . Ann. Neurol. . 59 . 3 . 527–34 . 2006 . 16453322 . 10.1002/ana.20749 . 10177664 . etal.
• Amann-Zalcenstein D, Avidan N, Kanyas K . AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia . Eur. J. Hum. Genet. . 14 . 10 . 1111–9 . 2006 . 16773125 . 10.1038/sj.ejhg.5201675 . etal. free .

Notes and References

1. Dixon-Salazar. Tracy. Silhavy. Jennifer L.. Marsh. Sarah E.. Louie. Carrie M.. Scott. Lesley C.. Gururaj. Aithala. Al-Gazali. Lihadh. Al-Tawari. Asma A.. Kayserili. Hulya. 2004-12-01. Mutations in the AHI1 Gene, Encoding Jouberin, Cause Joubert Syndrome with Cortical Polymicrogyria. American Journal of Human Genetics. 75. 6. 979–987. 0002-9297. 1182159. 15467982. 10.1086/425985.
2. Amann-Zalcenstein. Daniela. Avidan. Nili. Kanyas. Kyra. Ebstein. Richard P.. Kohn. Yoav. Hamdan. Adnan. Ben-Asher. Edna. Karni. Osnat. Mujaheed. Muhammed. 2006-06-14. AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia. European Journal of Human Genetics. en. 14. 10. 1111–1119. 10.1038/sj.ejhg.5201675. 1018-4813. 16773125. free.
3. Lotan. A. Lifschytz. T. Slonimsky. A. Broner. E C. Greenbaum. L. Abedat. S. Fellig. Y. Cohen. H. Lory. O. Neural mechanisms underlying stress resilience in Ahi1 knockout mice: relevance to neuropsychiatric disorders. Molecular Psychiatry. 19. 2. 243–252. 10.1038/mp.2013.123. 24042478. 2014. free.
4. Lagier-Tourenne C, Boltshauser E, Breivik N, Gribaa M, Betard C, Barbot C, Koenig M . Homozygosity mapping of a third Joubert syndrome locus to 6q23 . J Med Genet . 41 . 4 . 273–7 . Apr 2004 . 15060101 . 1735723 . 10.1136/jmg.2003.014787 .
5. Utsch B, Sayer JA, Attanasio M, Pereira RR, Eccles M, Hennies HC, Otto EA, Hildebrandt F . Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome . Pediatr Nephrol . 21 . 1 . 32–5 . Mar 2006 . 16240161 . 10.1007/s00467-005-2054-y . 2027.42/47827 . 18955859 . free .
6. Web site: Entrez Gene: AHI1 Abelson helper integration site 1.