Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer
Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosom...
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| Veröffentlicht in: | Molecular psychiatry 2009-06, Vol.14 (6), p.563-589 |
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| description | Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (
ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20
,
FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1
and
VMAT1/SLC18A1
) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (
Fgf17
) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence. |
| doi_str_mv | 10.1038/mp.2009.2 |
| format | Article |
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ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20
,
FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1
and
VMAT1/SLC18A1
) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (
Fgf17
) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/mp.2009.2</identifier><identifier>PMID: 19204725</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adult and adolescent clinical studies ; Alzheimer's disease ; Animals ; Autism ; Autistic Disorder - genetics ; Behavioral Sciences ; Biological and medical sciences ; Biological Psychology ; Bipolar disorder ; Cancer ; Child clinical studies ; Chromosome 8 ; Chromosomes, Human, Pair 8 ; Copy number ; Cytogenetics ; Developmental disorders ; Egr-3 protein ; feature-review ; Fibroblast growth factor 17 ; Fibroblast growth factor 20 ; Fibroblast growth factor receptor 1 ; Frizzled-related protein 1 ; Gene expression ; Gene Expression Regulation, Developmental ; Genetic aspects ; Genetic susceptibility ; Humans ; Infantile autism ; Medical sciences ; Medicine ; Medicine & Public Health ; Mental disorders ; miRNA ; Movement disorders ; Neoplasms - genetics ; Neural coding ; Neurodegenerative diseases ; Neurosciences ; Parkinson's disease ; Pharmacotherapy ; Prefrontal cortex ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychoses ; Risk factors ; Schizophrenia ; Schizophrenia - genetics ; Social behavior ; Tumor suppressor genes ; Tumors</subject><ispartof>Molecular psychiatry, 2009-06, Vol.14 (6), p.563-589</ispartof><rights>Springer Nature Limited 2009</rights><rights>2009 INIST-CNRS</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2009</rights><rights>Nature Publishing Group 2009.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c603t-b7b158393a4650c1ad751feabfc8e431ea0c97b2f0c5ad2552da0f161a0ae45a3</citedby><cites>FETCH-LOGICAL-c603t-b7b158393a4650c1ad751feabfc8e431ea0c97b2f0c5ad2552da0f161a0ae45a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/mp.2009.2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/mp.2009.2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21463935$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19204725$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tabarés-Seisdedos, R</creatorcontrib><creatorcontrib>Rubenstein, J L R</creatorcontrib><title>Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (
ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20
,
FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1
and
VMAT1/SLC18A1
) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (
Fgf17
) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence.</description><subject>Adult and adolescent clinical studies</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Autism</subject><subject>Autistic Disorder - genetics</subject><subject>Behavioral Sciences</subject><subject>Biological and medical sciences</subject><subject>Biological Psychology</subject><subject>Bipolar disorder</subject><subject>Cancer</subject><subject>Child clinical studies</subject><subject>Chromosome 8</subject><subject>Chromosomes, Human, Pair 8</subject><subject>Copy number</subject><subject>Cytogenetics</subject><subject>Developmental disorders</subject><subject>Egr-3 protein</subject><subject>feature-review</subject><subject>Fibroblast growth factor 17</subject><subject>Fibroblast growth factor 20</subject><subject>Fibroblast growth factor receptor 1</subject><subject>Frizzled-related protein 1</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genetic aspects</subject><subject>Genetic susceptibility</subject><subject>Humans</subject><subject>Infantile autism</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mental disorders</subject><subject>miRNA</subject><subject>Movement disorders</subject><subject>Neoplasms - genetics</subject><subject>Neural coding</subject><subject>Neurodegenerative diseases</subject><subject>Neurosciences</subject><subject>Parkinson's disease</subject><subject>Pharmacotherapy</subject><subject>Prefrontal cortex</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychoses</subject><subject>Risk factors</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>Social behavior</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp90s2P1CAUAPDGaNx19eA_YIhGjcaOQIG23jYTv5JNvOiZvNLXHTYFKrQm68k_XepMnPgZDpDH7z0gvKK4z-iG0ap56aYNp7Td8BvFKRO1KqWsm5t5Xcm2FKwRJ8WdlK4oXTfl7eKEtZyKmsvT4tt2F4MLKTgkzUQgESBTmNHPFkayWzoyhEh6_IJjmFwO56jHJYYpXZudhTlaQ3qbQuwxplfEumm0BmYbfPqRmrL6GqZdRG_hBYFltskR8D0x4A3Gu8WtAcaE9w7zWfHpzeuP23flxYe377fnF6VRtJrLru6YbKq2AqEkNQz6WrIBoRtMg6JiCNS0dccHaiT0XEreAx2YYkABhYTqrHi6rzvF8HnBNGtnk8FxBI9hSbqWommEqlmWT_4rVc2VrMQKH_0Gr8ISfX6F5krIWvJW8qwe_lNxxitZVc2x1CWMqK0fwhzBrOfqc04ZbZQSq9r8ReXRo7MmeBxsjv-S8GyfYGJIKeKgp2gdxGvNqF5bR7tJr62j13s-ONxz6Rz2R3nolQweHwAkA-MQ8__Z9NNxJlT-n9U937uUt_wlxuOD_zz1OxRo2Po</recordid><startdate>20090601</startdate><enddate>20090601</enddate><creator>Tabarés-Seisdedos, R</creator><creator>Rubenstein, J L R</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20090601</creationdate><title>Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer</title><author>Tabarés-Seisdedos, R ; Rubenstein, J L R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c603t-b7b158393a4650c1ad751feabfc8e431ea0c97b2f0c5ad2552da0f161a0ae45a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Alzheimer's disease</topic><topic>Animals</topic><topic>Autism</topic><topic>Autistic Disorder - genetics</topic><topic>Behavioral Sciences</topic><topic>Biological and medical sciences</topic><topic>Biological Psychology</topic><topic>Bipolar disorder</topic><topic>Cancer</topic><topic>Child clinical studies</topic><topic>Chromosome 8</topic><topic>Chromosomes, Human, Pair 8</topic><topic>Copy number</topic><topic>Cytogenetics</topic><topic>Developmental disorders</topic><topic>Egr-3 protein</topic><topic>feature-review</topic><topic>Fibroblast growth factor 17</topic><topic>Fibroblast growth factor 20</topic><topic>Fibroblast growth factor receptor 1</topic><topic>Frizzled-related protein 1</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genetic aspects</topic><topic>Genetic susceptibility</topic><topic>Humans</topic><topic>Infantile autism</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mental disorders</topic><topic>miRNA</topic><topic>Movement disorders</topic><topic>Neoplasms - genetics</topic><topic>Neural coding</topic><topic>Neurodegenerative diseases</topic><topic>Neurosciences</topic><topic>Parkinson's disease</topic><topic>Pharmacotherapy</topic><topic>Prefrontal cortex</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychoses</topic><topic>Risk factors</topic><topic>Schizophrenia</topic><topic>Schizophrenia - genetics</topic><topic>Social behavior</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tabarés-Seisdedos, R</creatorcontrib><creatorcontrib>Rubenstein, J L R</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tabarés-Seisdedos, R</au><au>Rubenstein, J L R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2009-06-01</date><risdate>2009</risdate><volume>14</volume><issue>6</issue><spage>563</spage><epage>589</epage><pages>563-589</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (
ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20
,
FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1
and
VMAT1/SLC18A1
) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (
Fgf17
) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19204725</pmid><doi>10.1038/mp.2009.2</doi><tpages>27</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular psychiatry, 2009-06, Vol.14 (6), p.563-589 |
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| language | eng |
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| subjects | Adult and adolescent clinical studies Alzheimer's disease Animals Autism Autistic Disorder - genetics Behavioral Sciences Biological and medical sciences Biological Psychology Bipolar disorder Cancer Child clinical studies Chromosome 8 Chromosomes, Human, Pair 8 Copy number Cytogenetics Developmental disorders Egr-3 protein feature-review Fibroblast growth factor 17 Fibroblast growth factor 20 Fibroblast growth factor receptor 1 Frizzled-related protein 1 Gene expression Gene Expression Regulation, Developmental Genetic aspects Genetic susceptibility Humans Infantile autism Medical sciences Medicine Medicine & Public Health Mental disorders miRNA Movement disorders Neoplasms - genetics Neural coding Neurodegenerative diseases Neurosciences Parkinson's disease Pharmacotherapy Prefrontal cortex Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Risk factors Schizophrenia Schizophrenia - genetics Social behavior Tumor suppressor genes Tumors |
| title | Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer |
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