Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat : a candidate for schizophrenia and bipolar disorder?
Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium chann...
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| Veröffentlicht in: | Molecular psychiatry 1998, Vol.3 (1), p.32-37 |
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| creator | CHANDY, K. G FANTINO, E MORRIS-ROSENDAHL, D. J GARGUS, J. J WITTEKINDT, O KALMAN, K TONG, L.-L HO, T.-H GUTMAN, G. A CROCQ, M.-A GANGULI, R NIMGAONKAR, V |
| description | Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that contains two arrays of CAG trinucleotide repeats. The second CAG repeat in hSKCa3 is highly polymorphic in control individuals, with alleles ranging in size from 12 to 28 repeats. The overall allele frequency distribution is significantly different in patients with schizophrenia compared to ethnically matched controls (Wilcoxon Rank Sum test, P=0.024), with CAG repeats longer than the modal value being over-represented in patients (Fisher Exact test, P=0.0035). A similar, non-significant, trend is seen for patients with bipolar disorder. These results provide evidence for a possible association between longer alleles in the hSKCa3 gene and both of these neuropsychiatric diseases, and emphasize the need for more extensive studies of this new gene. Small conductance calcium-activated K+ channels play a critical role in determining the firing pattern of neurons. These polyglutamine repeats may modulate hSKCa3 channel function and neuronal excitability, and thereby increase disease risk when combined with other genetic and environmental effects. |
| doi_str_mv | 10.1038/sj.mp.4000353 |
| format | Article |
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G ; FANTINO, E ; MORRIS-ROSENDAHL, D. J ; GARGUS, J. J ; WITTEKINDT, O ; KALMAN, K ; TONG, L.-L ; HO, T.-H ; GUTMAN, G. A ; CROCQ, M.-A ; GANGULI, R ; NIMGAONKAR, V</creator><creatorcontrib>CHANDY, K. G ; FANTINO, E ; MORRIS-ROSENDAHL, D. J ; GARGUS, J. J ; WITTEKINDT, O ; KALMAN, K ; TONG, L.-L ; HO, T.-H ; GUTMAN, G. A ; CROCQ, M.-A ; GANGULI, R ; NIMGAONKAR, V</creatorcontrib><description>Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that contains two arrays of CAG trinucleotide repeats. The second CAG repeat in hSKCa3 is highly polymorphic in control individuals, with alleles ranging in size from 12 to 28 repeats. The overall allele frequency distribution is significantly different in patients with schizophrenia compared to ethnically matched controls (Wilcoxon Rank Sum test, P=0.024), with CAG repeats longer than the modal value being over-represented in patients (Fisher Exact test, P=0.0035). A similar, non-significant, trend is seen for patients with bipolar disorder. These results provide evidence for a possible association between longer alleles in the hSKCa3 gene and both of these neuropsychiatric diseases, and emphasize the need for more extensive studies of this new gene. Small conductance calcium-activated K+ channels play a critical role in determining the firing pattern of neurons. These polyglutamine repeats may modulate hSKCa3 channel function and neuronal excitability, and thereby increase disease risk when combined with other genetic and environmental effects.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/sj.mp.4000353</identifier><identifier>PMID: 9491810</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Adult and adolescent clinical studies ; Alleles ; Amino Acid Sequence ; Biological and medical sciences ; Bipolar disorder ; Bipolar Disorder - genetics ; Brain - metabolism ; Calcium channels ; Calcium conductance ; Environmental effects ; Excitability ; Firing pattern ; Gene frequency ; Humans ; Medical sciences ; Mental disorders ; Molecular Sequence Data ; Neurodegenerative diseases ; Neurons - metabolism ; Neuropeptides - biosynthesis ; Neuropeptides - chemistry ; Neuropeptides - genetics ; Polyglutamine ; Polymorphism, Genetic ; Potassium ; Potassium channels (calcium-gated) ; Potassium Channels - biosynthesis ; Potassium Channels - chemistry ; Potassium Channels - genetics ; Potassium conductance ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychoses ; Schizophrenia ; Schizophrenia - genetics ; Sequence Alignment ; Sequence Homology, Amino Acid ; Small-Conductance Calcium-Activated Potassium Channels ; Trinucleotide repeat diseases ; Trinucleotide Repeats</subject><ispartof>Molecular psychiatry, 1998, Vol.3 (1), p.32-37</ispartof><rights>1999 INIST-CNRS</rights><rights>Macmillan Publishers Limited 1998.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-c1300b19876f5cded9547637e36670649cffb39fe552648a5ca94971eae679c03</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1871977$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9491810$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHANDY, K. G</creatorcontrib><creatorcontrib>FANTINO, E</creatorcontrib><creatorcontrib>MORRIS-ROSENDAHL, D. J</creatorcontrib><creatorcontrib>GARGUS, J. J</creatorcontrib><creatorcontrib>WITTEKINDT, O</creatorcontrib><creatorcontrib>KALMAN, K</creatorcontrib><creatorcontrib>TONG, L.-L</creatorcontrib><creatorcontrib>HO, T.-H</creatorcontrib><creatorcontrib>GUTMAN, G. A</creatorcontrib><creatorcontrib>CROCQ, M.-A</creatorcontrib><creatorcontrib>GANGULI, R</creatorcontrib><creatorcontrib>NIMGAONKAR, V</creatorcontrib><title>Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat : a candidate for schizophrenia and bipolar disorder?</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><description>Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that contains two arrays of CAG trinucleotide repeats. The second CAG repeat in hSKCa3 is highly polymorphic in control individuals, with alleles ranging in size from 12 to 28 repeats. The overall allele frequency distribution is significantly different in patients with schizophrenia compared to ethnically matched controls (Wilcoxon Rank Sum test, P=0.024), with CAG repeats longer than the modal value being over-represented in patients (Fisher Exact test, P=0.0035). A similar, non-significant, trend is seen for patients with bipolar disorder. These results provide evidence for a possible association between longer alleles in the hSKCa3 gene and both of these neuropsychiatric diseases, and emphasize the need for more extensive studies of this new gene. Small conductance calcium-activated K+ channels play a critical role in determining the firing pattern of neurons. These polyglutamine repeats may modulate hSKCa3 channel function and neuronal excitability, and thereby increase disease risk when combined with other genetic and environmental effects.</description><subject>Adult and adolescent clinical studies</subject><subject>Alleles</subject><subject>Amino Acid Sequence</subject><subject>Biological and medical sciences</subject><subject>Bipolar disorder</subject><subject>Bipolar Disorder - genetics</subject><subject>Brain - metabolism</subject><subject>Calcium channels</subject><subject>Calcium conductance</subject><subject>Environmental effects</subject><subject>Excitability</subject><subject>Firing pattern</subject><subject>Gene frequency</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mental disorders</subject><subject>Molecular Sequence Data</subject><subject>Neurodegenerative diseases</subject><subject>Neurons - metabolism</subject><subject>Neuropeptides - biosynthesis</subject><subject>Neuropeptides - chemistry</subject><subject>Neuropeptides - genetics</subject><subject>Polyglutamine</subject><subject>Polymorphism, Genetic</subject><subject>Potassium</subject><subject>Potassium channels (calcium-gated)</subject><subject>Potassium Channels - biosynthesis</subject><subject>Potassium Channels - chemistry</subject><subject>Potassium Channels - genetics</subject><subject>Potassium conductance</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychoses</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>Sequence Alignment</subject><subject>Sequence Homology, Amino Acid</subject><subject>Small-Conductance Calcium-Activated Potassium Channels</subject><subject>Trinucleotide repeat diseases</subject><subject>Trinucleotide Repeats</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkcFrFTEQxoMotVaPHoWA4m2fSbPZbLyU8tBaLHhQz2FedtLNYzeJya5Q_wb_aFO6KHiaMN9vvsnwEfKSsx1non9Xjrs57VrGmJDiETnlreoaKVX_uL6F1E3L-_YpeVbKkbF7UZ6QE91q3nN2Sn5flzjB4mOg0VGgIf7Eiaa4QCl-nakdIYTaucWAdPz6eQ-C2hgW8MGH2zqQ4nQ3x5xGb-n-8opmTAgLfV8lC2HwAyxIXcy02NH_imnMGDzQKtGDr8OQ6eBLzAPmi-fkiYOp4IutnpHvHz98239qbr5cXe8vbxrbSrY0lgvGDlz3qnPSDjhoWc8SCkXXKda12jp3ENqhlOdd24O0UO9VHAE7pS0TZ-Ttg2_K8ceKZTGzLxanCQLGtRhV4XMleQVf_wce45pD_ZupzlJJzZWqVPNA2RxLyehMyn6GfGc4M_cZmXI0czJbRpV_tbmuhxmHv_QWStXfbDoUC5PLEKwv_0x7xXVd-wes7poj</recordid><startdate>1998</startdate><enddate>1998</enddate><creator>CHANDY, K. G</creator><creator>FANTINO, E</creator><creator>MORRIS-ROSENDAHL, D. J</creator><creator>GARGUS, J. J</creator><creator>WITTEKINDT, O</creator><creator>KALMAN, K</creator><creator>TONG, L.-L</creator><creator>HO, T.-H</creator><creator>GUTMAN, G. A</creator><creator>CROCQ, M.-A</creator><creator>GANGULI, R</creator><creator>NIMGAONKAR, V</creator><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>7TK</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>1998</creationdate><title>Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat : a candidate for schizophrenia and bipolar disorder?</title><author>CHANDY, K. G ; FANTINO, E ; MORRIS-ROSENDAHL, D. J ; GARGUS, J. J ; WITTEKINDT, O ; KALMAN, K ; TONG, L.-L ; HO, T.-H ; GUTMAN, G. A ; CROCQ, M.-A ; GANGULI, R ; NIMGAONKAR, V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-c1300b19876f5cded9547637e36670649cffb39fe552648a5ca94971eae679c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Alleles</topic><topic>Amino Acid Sequence</topic><topic>Biological and medical sciences</topic><topic>Bipolar disorder</topic><topic>Bipolar Disorder - genetics</topic><topic>Brain - metabolism</topic><topic>Calcium channels</topic><topic>Calcium conductance</topic><topic>Environmental effects</topic><topic>Excitability</topic><topic>Firing pattern</topic><topic>Gene frequency</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mental disorders</topic><topic>Molecular Sequence Data</topic><topic>Neurodegenerative diseases</topic><topic>Neurons - metabolism</topic><topic>Neuropeptides - biosynthesis</topic><topic>Neuropeptides - chemistry</topic><topic>Neuropeptides - genetics</topic><topic>Polyglutamine</topic><topic>Polymorphism, Genetic</topic><topic>Potassium</topic><topic>Potassium channels (calcium-gated)</topic><topic>Potassium Channels - biosynthesis</topic><topic>Potassium Channels - chemistry</topic><topic>Potassium Channels - genetics</topic><topic>Potassium conductance</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychoses</topic><topic>Schizophrenia</topic><topic>Schizophrenia - genetics</topic><topic>Sequence Alignment</topic><topic>Sequence Homology, Amino Acid</topic><topic>Small-Conductance Calcium-Activated Potassium Channels</topic><topic>Trinucleotide repeat diseases</topic><topic>Trinucleotide Repeats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHANDY, K. G</creatorcontrib><creatorcontrib>FANTINO, E</creatorcontrib><creatorcontrib>MORRIS-ROSENDAHL, D. J</creatorcontrib><creatorcontrib>GARGUS, J. J</creatorcontrib><creatorcontrib>WITTEKINDT, O</creatorcontrib><creatorcontrib>KALMAN, K</creatorcontrib><creatorcontrib>TONG, L.-L</creatorcontrib><creatorcontrib>HO, T.-H</creatorcontrib><creatorcontrib>GUTMAN, G. A</creatorcontrib><creatorcontrib>CROCQ, M.-A</creatorcontrib><creatorcontrib>GANGULI, R</creatorcontrib><creatorcontrib>NIMGAONKAR, V</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>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHANDY, K. G</au><au>FANTINO, E</au><au>MORRIS-ROSENDAHL, D. J</au><au>GARGUS, J. J</au><au>WITTEKINDT, O</au><au>KALMAN, K</au><au>TONG, L.-L</au><au>HO, T.-H</au><au>GUTMAN, G. A</au><au>CROCQ, M.-A</au><au>GANGULI, R</au><au>NIMGAONKAR, V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat : a candidate for schizophrenia and bipolar disorder?</atitle><jtitle>Molecular psychiatry</jtitle><addtitle>Mol Psychiatry</addtitle><date>1998</date><risdate>1998</risdate><volume>3</volume><issue>1</issue><spage>32</spage><epage>37</epage><pages>32-37</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that contains two arrays of CAG trinucleotide repeats. The second CAG repeat in hSKCa3 is highly polymorphic in control individuals, with alleles ranging in size from 12 to 28 repeats. The overall allele frequency distribution is significantly different in patients with schizophrenia compared to ethnically matched controls (Wilcoxon Rank Sum test, P=0.024), with CAG repeats longer than the modal value being over-represented in patients (Fisher Exact test, P=0.0035). A similar, non-significant, trend is seen for patients with bipolar disorder. These results provide evidence for a possible association between longer alleles in the hSKCa3 gene and both of these neuropsychiatric diseases, and emphasize the need for more extensive studies of this new gene. Small conductance calcium-activated K+ channels play a critical role in determining the firing pattern of neurons. These polyglutamine repeats may modulate hSKCa3 channel function and neuronal excitability, and thereby increase disease risk when combined with other genetic and environmental effects.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>9491810</pmid><doi>10.1038/sj.mp.4000353</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult and adolescent clinical studies Alleles Amino Acid Sequence Biological and medical sciences Bipolar disorder Bipolar Disorder - genetics Brain - metabolism Calcium channels Calcium conductance Environmental effects Excitability Firing pattern Gene frequency Humans Medical sciences Mental disorders Molecular Sequence Data Neurodegenerative diseases Neurons - metabolism Neuropeptides - biosynthesis Neuropeptides - chemistry Neuropeptides - genetics Polyglutamine Polymorphism, Genetic Potassium Potassium channels (calcium-gated) Potassium Channels - biosynthesis Potassium Channels - chemistry Potassium Channels - genetics Potassium conductance Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Schizophrenia Schizophrenia - genetics Sequence Alignment Sequence Homology, Amino Acid Small-Conductance Calcium-Activated Potassium Channels Trinucleotide repeat diseases Trinucleotide Repeats |
| title | Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat : a candidate for schizophrenia and bipolar disorder? |
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