LRRTM1 explained

LRRTM1 is a brain-expressed imprinted gene that encodes a leucine-rich repeat transmembrane protein that interacts with neurexins and neuroligins to modulate synaptic cell adhesion in neurons.^{[1] [2]} As the name implies, its protein product is a transmembrane protein that contains many leucine rich repeats. It is expressed during the development of specific forebrain structures and shows a variable pattern of maternal downregulation (genomic imprinting).^{[3] [4]}

Clinical significance

LRRTM1 is the first gene linked to increased odds of being left-handed, when inherited from the father's side.^[5] Possessing one particular variant of the LRRTM1 gene slightly raises the risk of psychotic mental illnesses such as schizophrenia, again only if inherited from the father's side.^[5] As well, LRRTM1 has been associated with measures of schizotypy in non-clinical populations,^[6] indicating that the gene may have shared effects on neurodevelopment in both healthy and unhealthy individuals and individuals with schizophrenia.

LRRTM1 is also critically involved in synapse formation within the dorsal lateral geniculate nucleus (dLGN) of mice. LRRTM1 aids in the assembly of complex retinogenciulate synapses in mice, which are believed to help process complex visual signals. Lack of this gene shows decreased performance in complex visual tasks.^[7]

See also

• Handedness

Further reading

• Leach EL, Prefontaine G, Hurd PL, Crespi BJ . The imprinted gene LRRTM1 mediates schizotypy and handedness in a nonclinical population . Journal of Human Genetics . 59 . 6 . 332–6 . June 2014 . 24785688 . 10.1038/jhg.2014.30 . 6285226 . free .
• Sousa I, Clark TG, Holt R, Pagnamenta AT, Mulder EJ, Minderaa RB, Bailey AJ, Battaglia A, Klauck SM, Poustka F, Monaco AP . 6 . Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry . Molecular Autism . 1 . 1 . 7 . March 2010 . 20678249 . 2913944 . 10.1186/2040-2392-1-7 . free .
• Crow TJ, Close JP, Dagnall AM, Priddle TH . Where and what is the right shift factor or cerebral dominance gene? A critique of Francks et al. (2007) . Laterality . 14 . 1 . 3–10 . January 2009 . 19125366 . 10.1080/13576500802574984 . 770656 .
• 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 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A . 6 . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment . Genome Research . 13 . 10 . 2265–70 . October 2003 . 12975309 . 403697 . 10.1101/gr.1293003 .
• Ludwig KU, Mattheisen M, Mühleisen TW, Roeske D, Schmäl C, Breuer R, Schulte-Körne G, Müller-Myhsok B, Nöthen MM, Hoffmann P, Rietschel M, Cichon S . 6 . Supporting evidence for LRRTM1 imprinting effects in schizophrenia . Molecular Psychiatry . 14 . 8 . 743–5 . August 2009 . 19626025 . 10.1038/mp.2009.28 . 205201798 .
• McManus C, Nicholls M, Vallortigara G . Editorial commentary: is LRRTM1 the gene for handedness? . Laterality . 14 . 1 . 1–2 . January 2009 . 19125365 . 10.1080/13576500802542577 . 8667174 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Francks C . Understanding the genetics of behavioural and psychiatric traits will only be achieved through a realistic assessment of their complexity . Laterality . 14 . 1 . 11–6 . January 2009 . 19125367 . 10.1080/13576500802536439 . 11858/00-001M-0000-0012-C72F-9 . 17388449 . free .

Notes and References

1. Siddiqui TJ, Pancaroglu R, Kang Y, Rooyakkers A, Craig AM . LRRTMs and neuroligins bind neurexins with a differential code to cooperate in glutamate synapse development . The Journal of Neuroscience . 30 . 22 . 7495–506 . June 2010 . 20519524 . 2896269 . 10.1523/JNEUROSCI.0470-10.2010 .
2. Soler-Llavina GJ, Fuccillo MV, Ko J, Südhof TC, Malenka RC . The neurexin ligands, neuroligins and leucine-rich repeat transmembrane proteins, perform convergent and divergent synaptic functions in vivo . Proceedings of the National Academy of Sciences of the United States of America . 108 . 40 . 16502–9 . October 2011 . 21953696 . 3189075 . 10.1073/pnas.1114028108 . free .
3. Web site: Entrez Gene: leucine rich repeat transmembrane neuronal 1.
4. Laurén J, Airaksinen MS, Saarma M, Timmusk T . A novel gene family encoding leucine-rich repeat transmembrane proteins differentially expressed in the nervous system . Genomics . 81 . 4 . 411–21 . April 2003 . 12676565 . 10.1016/S0888-7543(03)00030-2 .
5. Francks C, Maegawa S, Laurén J, Abrahams BS, Velayos-Baeza A, Medland SE, Colella S, Groszer M, McAuley EZ, Caffrey TM, Timmusk T, Pruunsild P, Koppel I, Lind PA, Matsumoto-Itaba N, Nicod J, Xiong L, Joober R, Enard W, Krinsky B, Nanba E, Richardson AJ, Riley BP, Martin NG, Strittmatter SM, Möller HJ, Rujescu D, St Clair D, Muglia P, Roos JL, Fisher SE, Wade-Martins R, Rouleau GA, Stein JF, Karayiorgou M, Geschwind DH, Ragoussis J, Kendler KS, Airaksinen MS, Oshimura M, DeLisi LE, Monaco AP . 6 . LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia . Molecular Psychiatry . 12 . 12 . 1129–39, 1057 . December 2007 . 17667961 . 2990633 . 10.1038/sj.mp.4002053.
   • News: 31 July 2007 . Gene for left-handedness is found . BBC News .
6. Leach EL, Prefontaine G, Hurd PL, Crespi BJ . The imprinted gene LRRTM1 mediates schizotypy and handedness in a nonclinical population . Journal of Human Genetics . 59 . 6 . 332–6 . June 2014 . 24785688 . 10.1038/jhg.2014.30 . 6285226 . Bernard Crespi . free .
7. Van Name. Jonathan. Monavarfeshani. Aboozar. Fox. Michael. The role of complex retinogeniculate synapses in mouse visual behavior. July 2017.