The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders

Trends in Neurosciences

Volumn 32, Issue 7, 2009, Pages 402-412

  Betancur, Catalina ^a   Sakurai, Takeshi ^b   Buxbaum, Joseph D ^b  

^a INSERM   (France)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL ADHESION MOLECULE; CONTACTIN; CONTACTIN ASSOCIATED PROTEIN 1; CONTACTIN ASSOCIATED PROTEIN 2; CONTACTIN ASSOCIATED PROTEIN 3; CONTACTIN ASSOCIATED PROTEIN 4; CONTACTIN ASSOCIATED PROTEIN 5; FRAGILE X MENTAL RETARDATION PROTEIN; MEMBRANE PROTEIN; NERVE CELL ADHESION MOLECULE; NERVE CELL ADHESION MOLECULE 15; NEUREXIN; NEUREXIN 1; NEUREXIN 2; NEUREXIN 3; NEUROLIGIN; NEUROLIGIN 1; NEUROLIGIN 3; NEUROLIGIN 4X; NEUROLIGIN 4Y; PROTOCADHERIN; PROTOCADHERIN 19; PROTOCADHERIN 8; RAPAMYCIN; SCAFFOLD PROTEIN; SH3 AND MULTIPLE ANKYRIN REPEAT DOMAIN 3; UNCLASSIFIED DRUG;

AUTISM; CELL ADHESION; CELL MATURATION; CHROMOSOME TRANSLOCATION; DISEASE PREDISPOSITION; ENDOPLASMIC RETICULUM; FRAMESHIFT MUTATION; GENE DELETION; GENE DISRUPTION; GENE EXPRESSION; GENE LOCUS; GENE MUTATION; GENE REPLICATION; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; MISSENSE MUTATION; NERVE FIBER GROWTH; NONHUMAN; PATHOGENESIS; PHENOTYPE; POSTSYNAPTIC POTENTIAL; PRESYNAPTIC POTENTIAL; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN VARIANT; REVIEW; SIGNAL TRANSDUCTION; SOMATOSENSORY CORTEX; SYNAPSE; SYNAPTIC TRANSMISSION;

ANIMALS; AUTISTIC DISORDER; CELL ADHESION; CELL ADHESION MOLECULES; GENETIC PREDISPOSITION TO DISEASE; HUMANS; SIGNAL TRANSDUCTION; SYNAPSES;

EID: 67649400549     PISSN: 01662236     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tins.2009.04.003     Document Type: Review

References (141)

1. Fombonne E. Epidemiology of autistic disorder and other pervasive developmental disorders. J. Clin. Psychiatry 66 Suppl 10 (2005) 3-8
2. Abrahams B.S., and Geschwind D.H. Advances in autism genetics: on the threshold of a new neurobiology. Nat. Rev. Genet. 9 (2008) 341-355
3. Sebat J., et al. Strong association of de novo copy number mutations with autism. Science 316 (2007) 445-449
4. Marshall C.R., et al. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 82 (2008) 477-488
5. Chelly J., et al. Genetics and pathophysiology of mental retardation. Eur. J. Hum. Genet. 14 (2006) 701-713
6. Chiurazzi P., et al. XLMR genes: update 2007. Eur. J. Hum. Genet. 16 (2008) 422-434
7. Blanpied T.A., and Ehlers M.D. Microanatomy of dendritic spines: emerging principles of synaptic pathology in psychiatric and neurological disease. Biol. Psychiatry 55 (2004) 1121-1127
8. Scheiffele P. Cell-cell signaling during synapse formation in the CNS. Annu. Rev. Neurosci. 26 (2003) 485-508
9. Gerrow K., and El-Husseini A. Cell adhesion molecules at the synapse. Front. Biosci. 11 (2006) 2400-2419
10. Okabe S. Molecular anatomy of the postsynaptic density. Mol. Cell. Neurosci. 34 (2007) 503-518
11. Chih B., et al. Control of excitatory and inhibitory synapse formation by neuroligins. Science 307 (2005) 1324-1328
12. Jamain S., et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet. 34 (2003) 27-29
13. Chih B., et al. Disorder-associated mutations lead to functional inactivation of neuroligins. Hum. Mol. Genet. 13 (2004) 1471-1477
14. Comoletti D., et al. The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing. J. Neurosci. 24 (2004) 4889-4893
15. Chubykin A.A., et al. Dissection of synapse induction by neuroligins: effect of a neuroligin mutation associated with autism. J. Biol. Chem. 280 (2005) 22365-22374
16. Chubykin A.A., et al. Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2. Neuron 54 (2007) 919-931
17. Laumonnier F., et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am. J. Hum. Genet. 74 (2004) 552-557
18. Vincent J.B., et al. Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 129B (2004) 82-84
19. Gauthier J., et al. NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 132B (2005) 74-75
20. Ylisaukko-oja T., et al. Analysis of four neuroligin genes as candidates for autism. Eur. J. Hum. Genet. 13 (2005) 1285-1292
21. Blasi F., et al. Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 141B (2006) 220-221
22. Wermter A.K., et al. No evidence for involvement of genetic variants in the X-linked neuroligin genes NLGN3 and NLGN4X in probands with autism spectrum disorder on high functioning level. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 147B (2008) 535-537
23. Yan J., et al. Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol. Psychiatry 10 (2005) 329-332
24. Talebizadeh Z., et al. Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism. J. Med. Genet. 43 (2006) e21
25. Chocholska S., et al. Molecular cytogenetic analysis of a familial interstitial deletion Xp22.2-22. 3 with a highly variable phenotype in female carriers. Am. J. Med. Genet. A. 140 (2006) 604-610
26. Macarov M., et al. Deletions of VCX-A and NLGN4: a variable phenotype including normal intellect. J. Intellect. Disabil. Res. 51 (2007) 329-333
27. Lawson-Yuen A., et al. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur. J. Hum. Genet. 16 (2008) 614-618
28. Kent L., et al. X-linked ichthyosis (steroid sulfatase deficiency) is associated with increased risk of attention deficit hyperactivity disorder, autism and social communication deficits. J. Med. Genet. 45 (2008) 519-524
29. Mochel F., et al. Normal intelligence and social interactions in a male patient despite the deletion of NLGN4X and the VCX genes. Eur. J. Med. Genet. 51 (2008) 68-73
30. Tabuchi K., et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318 (2007) 71-76
31. Chadman K.K., et al. Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knock-in mice. Autism Res. 1 (2008) 147-158
32. Radyushkin K., et al. Neuroligin-3 deficient mice: Model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav. (2009). www.interscience.wiley.com 10.1111/j.1601-183X.2009.00487.x
33. Jamain S., et al. Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 1710-1715
34. Varoqueaux F., et al. Neuroligins determine synapse maturation and function. Neuron 51 (2006) 741-754
35. Sudhof T.C. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455 (2008) 903-911
36. Ichtchenko K., et al. Neuroligin 1: a splice site-specific ligand for β-neurexins. Cell 81 (1995) 435-443
37. Scheiffele P., et al. Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101 (2000) 657-669
38. Dean C., et al. Neurexin mediates the assembly of presynaptic terminals. Nat. Neurosci. 6 (2003) 708-716
39. Graf E.R., et al. Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 119 (2004) 1013-1026
40. Taniguchi H., et al. Silencing of neuroligin function by postsynaptic neurexins. J. Neurosci. 27 (2007) 2815-2824
41. Kattenstroth G., et al. Postsynaptic N-methyl-d-aspartate receptor function requires α-neurexins. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 2607-2612
42. Autism Genome Project Consortium. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat. Genet. 39 (2007) 319-328
43. Zahir F.R., et al. A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1α. J. Med. Genet. 45 (2008) 239-243
44. Glessner J.T., et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459 (2009) 569-573
45. Kim H.G., et al. Disruption of neurexin 1 associated with autism spectrum disorder. Am. J. Hum. Genet. 82 (2008) 199-207
46. Feng J., et al. High frequency of neurexin 1β signal peptide structural variants in patients with autism. Neurosci. Lett. 409 (2006) 10-13
47. Yan J., et al. Neurexin 1α structural variants associated with autism. Neurosci. Lett. 438 (2008) 368-370
48. Redon R., et al. Global variation in copy number in the human genome. Nature 444 (2006) 444-454
49. Rujescu D., et al. Disruption of the neurexin 1 gene is associated with schizophrenia. Hum. Mol. Genet. 18 (2009) 988-996
50. 2+ channels to synaptic vesicle exocytosis. Nature 423 (2003) 939-948
51. Dudanova I., et al. Deletion of α-neurexins does not cause a major impairment of axonal pathfinding or synapse formation. J. Comp. Neurol. 502 (2007) 261-274
52. 2+ channels. J. Neurosci. 25 (2005) 4330-4342
53. Samuels B.A., et al. Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK. Neuron 56 (2007) 823-837
54. Venturin M., et al. Mutations and novel polymorphisms in coding regions and UTRs of CDK5R1 and OMG genes in patients with non-syndromic mental retardation. Neurogenetics 7 (2006) 59-66
55. Froyen G., et al. Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes. Hum. Mutat. 28 (2007) 1034-1042
56. Najm J., et al. Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat. Genet. 40 (2008) 1065-1067
57. Sugiyama Y., et al. Determination of absolute protein numbers in single synapses by a GFP-based calibration technique. Nat. Methods 2 (2005) 677-684
58. Boeckers T.M. The postsynaptic density. Cell Tissue Res. 326 (2006) 409-422
59. Sheng M., and Hoogenraad C.C. The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu. Rev. Biochem. 76 (2007) 823-847
60. Meyer G., et al. The complexity of PDZ domain-mediated interactions at glutamatergic synapses: a case study on neuroligin. Neuropharmacology 47 (2004) 724-733
61. Gerrow K., et al. A preformed complex of postsynaptic proteins is involved in excitatory synapse development. Neuron 49 (2006) 547-562
62. Sala C., et al. Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron 31 (2001) 115-130
63. Roussignol G., et al. Shank expression is sufficient to induce functional dendritic spine synapses in aspiny neurons. J. Neurosci. 25 (2005) 3560-3570
64. Cusmano-Ozog K., et al. 22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay. Am. J. Med. Genet. C. Semin. Med. Genet. 145C (2007) 393-398
65. Wilson H.L., et al. Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J. Med. Genet. 40 (2003) 575-584
66. Bonaglia M.C., et al. Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13. 3) is associated with the 22q13. 3 deletion syndrome. Am. J. Hum. Genet. 69 (2001) 261-268
67. Bonaglia M.C., et al. Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome. J. Med. Genet. 43 (2006) 822-828
68. Durand C.M., et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat. Genet. 39 (2007) 25-27
69. Philippe A., et al. Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. Pediatrics 122 (2008) e376-e382
70. Jeffries A.R., et al. Molecular and phenotypic characterization of ring chromosome 22. Am. J. Med. Genet. A. 137 (2005) 139-147
71. Manning M.A., et al. Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 114 (2004) 451-457
72. Moessner R., et al. Contribution of SHANK3 mutations to autism spectrum disorder. Am. J. Hum. Genet. 81 (2007) 1289-1297
73. Gauthier J., et al. Novel de novo SHANK3 mutation in autistic patients. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 150B (2009) 421-424
74. Hung A.Y., et al. Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J. Neurosci. 28 (2008) 1697-1708
75. Redies C., et al. Cadherins as regulators for the emergence of neural nets from embryonic divisions. J. Physiol. (Paris) 97 (2003) 5-15
76. Arikkath J., and Reichardt L.F. Cadherins and catenins at synapses: roles in synaptogenesis and synaptic plasticity. Trends Neurosci. 31 (2008) 487-494
77. Benson D.L., and Tanaka H. N-cadherin redistribution during synaptogenesis in hippocampal neurons. J. Neurosci. 18 (1998) 6892-6904
78. Phillips G.R., et al. γ-protocadherins are targeted to subsets of synapses and intracellular organelles in neurons. J. Neurosci. 23 (2003) 5096-5104
79. Weiner J.A., et al. γ protocadherins are required for synaptic development in the spinal cord. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 8-14
80. Morrow E.M., et al. Identifying autism loci and genes by tracing recent shared ancestry. Science 321 (2008) 218-223
81. Dibbens L.M., et al. X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat. Genet. 40 (2008) 776-781
82. Bhalla K., et al. Alterations in CDH15 and KIRREL3 in patients with mild to severe intellectual disability. Am. J. Hum. Genet. 83 (2008) 703-713
83. Weiss L.A., et al. Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358 (2008) 667-675
84. Kumar R.A., et al. Recurrent 16p11.2 microdeletions in autism. Hum. Mol. Genet. 17 (2008) 628-638
85. Yasuda S., et al. Activity-induced protocadherin arcadlin regulates dendritic spine number by triggering N-cadherin endocytosis via TAO2β and p38 MAP kinases. Neuron 56 (2007) 456-471
86. Maness P.F., and Schachner M. Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration. Nat. Neurosci. 10 (2007) 19-26
87. Schmid R.S., and Maness P.F. L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth. Curr. Opin. Neurobiol. 18 (2008) 245-250
88. Kenwrick S., et al. Neural cell recognition molecule L1: relating biological complexity to human disease mutations. Hum. Mol. Genet. 9 (2000) 879-886
89. Karagogeos D. Neural GPI-anchored cell adhesion molecules. Front. Biosci. 8 (2003) s1304-s1320
90. Fernandez T., et al. Disruption of contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome. Am. J. Hum. Genet. 74 (2004) 1286-1293
91. Roohi J., et al. Disruption of contactin 4 in 3 subjects with autism spectrum disorder. J. Med. Genet. 46 (2009) 176-182
92. Yoshihara Y., et al. Overlapping and differential expression of BIG-2, BIG-1, TAG-1, and F3: four members of an axon-associated cell adhesion molecule subgroup of the immunoglobulin superfamily. J. Neurobiol. 28 (1995) 51-69
93. Pillai A.M., et al. No effect of genetic deletion of contactin-associated protein (CASPR) on axonal orientation and synaptic plasticity. J. Neurosci. Res. 85 (2007) 2318-2331
94. Bakkaloglu B., et al. Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am. J. Hum. Genet. 82 (2008) 165-173
95. + channels in myelinated axons depends on Caspr2 and TAG-1. J. Cell Biol. 162 (2003) 1149-1160
96. Traka M., et al. Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers. J. Cell Biol. 162 (2003) 1161-1172
97. Alarcon M., et al. Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am. J. Hum. Genet. 82 (2008) 150-159
98. Strauss K.A., et al. Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2. N. Engl. J. Med. 354 (2006) 1370-1377
99. Rossi E., et al. A 12Mb deletion at 7q33-q35 associated with autism spectrum disorders and primary amenorrhea. Eur. J. Med. Genet. 51 (2008) 631-638
100. Verkerk A.J., et al. CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder. Genomics 82 (2003) 1-9
101. Willatt L., et al. 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome. Am. J. Hum. Genet. 77 (2005) 154-160
102. Kakunaga S., et al. Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes. J. Cell Sci. 118 (2005) 1267-1277
103. Mizoguchi A., et al. Nectin: an adhesion molecule involved in formation of synapses. J. Cell Biol. 156 (2002) 555-565
104. Losh M., et al. Defining key features of the broad autism phenotype: a comparison across parents of multiple- and single-incidence autism families. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 147B (2008) 424-433
105. Virkud Y.V., et al. Familial aggregation of quantitative autistic traits in multiplex versus simplex autism. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 150B (2009) 328-334
106. Arking D.E., et al. A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am. J. Hum. Genet. 82 (2008) 160-164
107. Bonora E., et al. Mutation screening and association analysis of six candidate genes for autism on chromosome 7q. Eur. J. Hum. Genet. 13 (2005) 198-207
108. Sakurai T., et al. Association analysis of the NrCAM gene in autism and in subsets of families with severe obsessive-compulsive or self-stimulatory behaviors. Psychiatr. Genet. 16 (2006) 251-257
109. Marui T., et al. Association of the neuronal cell adhesion molecule (NRCAM) gene variants with autism. Int. J. Neuropsychopharmacol. 12 (2009) 1-10
110. Fatemi S.H. Reelin glycoprotein: structure, biology and roles in health and disease. Mol. Psychiatry 10 (2005) 251-257
111. Wang K., et al. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature 459 (2009) 528-533
112. Fiala J.C., et al. Dendritic spine pathology: cause or consequence of neurological disorders?. Brain Res. Brain Res. Rev. 39 (2002) 29-54
113. Ethell I.M., and Pasquale E.B. Molecular mechanisms of dendritic spine development and remodeling. Prog. Neurobiol. 75 (2005) 161-205
114. Zoghbi H.Y. Postnatal neurodevelopmental disorders: meeting at the synapse?. Science 302 (2003) 826-830
115. Rubenstein J.L., and Merzenich M.M. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav. 2 (2003) 255-267
116. Huang Z.J., and Scheiffele P. GABA and neuroligin signaling: linking synaptic activity and adhesion in inhibitory synapse development. Curr. Opin. Neurobiol. 18 (2008) 77-83
117. Minshew N.J., and Williams D.L. The new neurobiology of autism: cortex, connectivity, and neuronal organization. Arch. Neurol. 64 (2007) 945-950
118. Reddy K.S. Cytogenetic abnormalities and fragile-X syndrome in autism spectrum disorder. BMC Med. Genet. 6 (2005) 3
119. Clifford S., et al. Autism spectrum phenotype in males and females with fragile X full mutation and premutation. J. Autism Dev. Disord. 37 (2007) 738-747
120. Dictenberg J.B., et al. A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. Dev. Cell 14 (2008) 926-939
121. Bear M.F., et al. The mGluR theory of fragile X mental retardation. Trends Neurosci. 27 (2004) 370-377
122. Yan Q.J., et al. Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49 (2005) 1053-1066
123. Dolen G., et al. Correction of fragile X syndrome in mice. Neuron 56 (2007) 955-962
124. Nakamoto M., et al. Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc. Natl. Acad. Sci. U. S. A 104 (2007) 15537-15542
125. de Vrij F.M., et al. Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol. Dis. 31 (2008) 127-132
126. Guy J., et al. Reversal of neurological defects in a mouse model of Rett syndrome. Science 315 (2007) 1143-1147
127. Giacometti E., et al. Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 1931-1936
128. Tropea D., et al. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc. Natl. Acad. Sci. U. S. A. 106 (2009) 2029-2034
129. Ehninger D., et al. Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis. Nat. Med. 14 (2008) 843-848
130. Zhou J., et al. Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice. J. Neurosci. 29 (2009) 1773-1783
131. Zeng L.H., et al. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann. Neurol. 63 (2008) 444-453
132. Chow D.K., et al. Laminar and compartmental regulation of dendritic growth in mature cortex. Nat. Neurosci. 12 (2009) 116-118
133. Schmidt H., et al. Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial. J. Med. Genet. 46 (2009) 217-222
134. Reich D.E., and Lander E.S. On the allelic spectrum of human disease. Trends Genet. 17 (2001) 502-510
135. Pritchard J.K. Are rare variants responsible for susceptibility to complex diseases?. Am. J. Hum. Genet. 69 (2001) 124-137
136. Pritchard J.K., and Cox N.J. The allelic architecture of human disease genes: common disease-common variant... or not?. Hum. Mol. Genet. 11 (2002) 2417-2423
137. Bodmer W., and Bonilla C. Common and rare variants in multifactorial susceptibility to common diseases. Nat. Genet. 40 (2008) 695-701
138. Friedman J.I., et al. CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy. Mol. Psychiatry 13 (2008) 261-266
139. Lachman H.M., et al. Analysis of protocadherin α gene deletion variant in bipolar disorder and schizophrenia. Psychiatr. Genet. 18 (2008) 110-115
140. Brennaman L.H., and Maness P.F. NCAM in neuropsychiatric and neurodegenerative disorders. Neurochem. Res. (2008). www.springerlink.com 10.1007/s11064-008-9630-z
141. O'Donovan M.C., et al. Phenotypic variations on the theme of CNVs. Nat. Genet. 40 (2008) 1392-1393