Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
17667961
TITLE
LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia.
ABSTRACT
Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.
DATE PUBLISHED
2007 Dec
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2007/07/31
pubmed 2007/08/02 09:00
medline 2008/03/06 09:00
entrez 2007/08/02 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Francks C Francks C C Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. clyde.francks@well.ox.ac.uk
Maegawa S Maegawa S S
Laurén J Laurén J J
Abrahams BS Abrahams B S BS
Velayos-Baeza A Velayos-Baeza A A
Medland SE Medland S E SE
Colella S Colella S S
Groszer M Groszer M M
McAuley EZ McAuley E Z EZ
Caffrey TM Caffrey T M TM
Timmusk T Timmusk T T
Pruunsild P Pruunsild P P
Koppel I Koppel I I
Lind PA Lind P A PA
Matsumoto-Itaba N Matsumoto-Itaba N N
Nicod J Nicod J J
Xiong L Xiong L L
Joober R Joober R R
Enard W Enard W W
Krinsky B Krinsky B B
Nanba E Nanba E E
Richardson AJ Richardson A J AJ
Riley BP Riley B P BP
Martin NG Martin N G NG
Strittmatter SM Strittmatter S M SM
Möller HJ Möller H-J HJ
Rujescu D Rujescu D D
St Clair D St Clair D D
Muglia P Muglia P P
Roos JL Roos J L JL
Fisher SE Fisher S E SE
Wade-Martins R Wade-Martins R R
Rouleau GA Rouleau G A GA
Stein JF Stein J F JF
Karayiorgou M Karayiorgou M M
Geschwind DH Geschwind D H DH
Ragoussis J Ragoussis J J
Kendler KS Kendler K S KS
Airaksinen MS Airaksinen M S MS
Oshimura M Oshimura M M
DeLisi LE DeLisi L E LE
Monaco AP Monaco A P AP
INVESTIGATORS
JOURNAL
VOLUME: 12
ISSUE: 12
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2007
MONTH: Dec
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 1359-4184
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
073141 Wellcome Trust United Kingdom
G9826762 Medical Research Council United Kingdom
MH41953 NIMH NIH HHS United States
MH61399 NIMH NIH HHS United States
R01 MH-44245 NIMH NIH HHS United States
R01 MH041953 NIMH NIH HHS United States
R01 NS039962 NINDS NIH HHS United States
R01 NS039962-10 NINDS NIH HHS United States
R01 NS042304 NINDS NIH HHS United States
R01 NS042304-08 NINDS NIH HHS United States
R37 NS033020 NINDS NIH HHS United States
R37 NS033020-17 NINDS NIH HHS United States
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Animals
Brain pathology
Cell Line, Transformed pathology
Chromosomes, Human, Pair 2 pathology
Family Health pathology
Female pathology
Functional Laterality genetics
Gene Expression Regulation, Developmental physiology
Genetic Predisposition to Disease physiology
Genotype physiology
Humans physiology
In Situ Hybridization methods
Karyotyping methods
Male methods
Membrane Proteins metabolism
Mice metabolism
Nerve Tissue Proteins metabolism
Schizophrenia pathology
Subcellular Fractions ultrastructure
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 LRRTM1 protein, human
0 Membrane Proteins
0 Nerve Tissue Proteins
OTHER ID's
OTHERID SOURCE
NIHMS162885 NLM
PMC2990633 NLM
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