title: Expression and genetic variability of PCDH11Y, a gene specific to Homo sapiens and candidate for susceptibility to psychiatric disorders.
abstract: Synaptogenesis, the formation of functional synapses, is a crucial step for the development of the central nervous system. Among the genes involved in this process are cell adhesion molecules, such as protocadherins and neuroligins, which are essential factors for the identification of the appropriate partner cell and the formation of synapses. In this work, we studied the expression and the genetic variability of two closely related members of the protocadherin family PCDH11X/Y, located on the X and the Y chromosome, respectively. PCDH11Y is one of the rare genes specific to the hominoid lineage, being absent in other primates. Expression analysis indicated that transcripts of the PCDH11X/Y genes are mainly detected in the cortex of the human brain. Mutation screening of 30 individuals with autism identified two PCDH11Y polymorphic amino acid changes, F885V and K980N. These variations are in complete association, appeared during human evolution approximately 40,000 years ago and represent informative polymorphisms to study Y chromosome variability in populations. We studied the frequency of these variants in males with autism spectrum disorders (n = 110), attention deficit hyperactivity disorder (ADHD; n = 61), bipolar disorder (n = 61), obsessive-compulsive disorder (n = 51), or schizophrenia (n = 61) and observed no significant differences when compared to ethnically-matched control populations. These findings do not support the role of PCDH11Y, or more generally of a frequent specific Y chromosome, in the susceptibility to these neuropsychiatric disorders.
authors.affiliation: Human Genetics and Cognitive Functions, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Christelle M
authors.initials: CM
authors.lastname: Durand
authors.forename: Caroline
authors.initials: C
authors.lastname: Kappeler
authors.forename: Catalina
authors.initials: C
authors.lastname: Betancur
authors.forename: Richard
authors.initials: R
authors.lastname: Delorme
authors.forename: Hélène
authors.initials: H
authors.lastname: Quach
authors.forename: Hany
authors.initials: H
authors.lastname: Goubran-Botros
authors.forename: Jonas
authors.initials: J
authors.lastname: Melke
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nygren
authors.forename: Nadia
authors.initials: N
authors.lastname: Chabane
authors.forename: Franck
authors.initials: F
authors.lastname: Bellivier
authors.forename: Andrei
authors.initials: A
authors.lastname: Szoke
authors.forename: Franck
authors.initials: F
authors.lastname: Schurhoff
authors.forename: Maria
authors.initials: M
authors.lastname: Rastam
authors.forename: Henrik
authors.initials: H
authors.lastname: Anckarsäter
authors.forename: Christopher
authors.initials: C
authors.lastname: Gillberg
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Bourgeron
mesh_terms: D000595:Amino Acid Sequence; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D001921:Brain / Q000378:metabolism; D015820:Cadherins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005602:France; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D000091363:Protocadherins; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013548:Sweden
chemical_list: D015820:Cadherins; C468654:PCDH11Y protein, human; D000091363:Protocadherins; D012313:RNA