Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene
The silent phenotype of human butyrylcholinesterase (BChE), present in most human populations in frequencies of approximately 1/100,000, is characterized by the complete absence of BChE activity or by activity
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| Veröffentlicht in: | American journal of human genetics 1996, Vol.58 (1), p.52-64 |
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| container_title | American journal of human genetics |
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| creator | PRIMO-PARMO, S. L BARTELS, C. F WIERSEMA, B VAN DER SPEK, A. F. L INNIS, J. W LA DU, B. N |
| description | The silent phenotype of human butyrylcholinesterase (BChE), present in most human populations in frequencies of approximately 1/100,000, is characterized by the complete absence of BChE activity or by activity |
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| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1914969</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17038283</sourcerecordid><originalsourceid>FETCH-LOGICAL-p321t-e1a121d268eddb51cfcaef4c45ff294396ba9b2903e533f98498d1458563c8ea3</originalsourceid><addsrcrecordid>eNpVkE1Lw0AQhhdRaq3-BCEHET0E9iO73b0IGuoHFLzUc5hsJs3KJqnZRKi_3oih6Glgnnfed2aOyJxJsYyVovKYzCmlPDbcLE_JWQjvlDKmqZiRmZYyoUrPySatoAPbY-e-oHdtE7VlxHgUnMemj8B79Bh-mn2FUTXU0ET50O-7vbdV612DYZyFgNHNQ_q8uo222OA5OSnBB7yY6oK8Pa426XO8fn16Se_X8U5w1sfIgHFWcKWxKHLJbGkBy8Qmsiy5SYRROZicGypQClEanRhdsERqqYTVCGJB7n59d0NeY2HHjTvw2a5zNXT7rAWX_SeNq7Jt-5kxwxKjzGhwPRl07ccwnpLVLlj0Hhpsh5CxJRWaazEKL_8mHSKmP478auIQLPiyg8a6cJAJypXgXHwDcEh9pA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17038283</pqid></control><display><type>article</type><title>Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>ScienceDirect Journals (5 years ago - present)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>PRIMO-PARMO, S. L ; BARTELS, C. F ; WIERSEMA, B ; VAN DER SPEK, A. F. L ; INNIS, J. W ; LA DU, B. N</creator><creatorcontrib>PRIMO-PARMO, S. L ; BARTELS, C. F ; WIERSEMA, B ; VAN DER SPEK, A. F. L ; INNIS, J. W ; LA DU, B. N</creatorcontrib><description>The silent phenotype of human butyrylcholinesterase (BChE), present in most human populations in frequencies of approximately 1/100,000, is characterized by the complete absence of BChE activity or by activity <10% of the average levels of the usual phenotype. Heterogeneity in this phenotype has been well established at the phenotypic level, but only a few silent BCHE alleles have been characterized at the DNA level. Twelve silent alleles of the human butyrylcholinesterase gene (BCHE) have been identified in 17 apparently unrelated patients who were selected by their increased sensitivity to the muscle relaxant succinylcholine. All of these alleles are characterized by single nucleotide substitutions or deletions leading to distinct changes in the structure of the BChE enzyme molecule. Nine of the nucleotide substitutions result in the replacement of single amino acid residues. Three of these variants, BCHE*33C, BCHE*198G, and BCHE*201T, produce normal amounts of immunoreactive but enzymatically inactive BChE protein in the plasma. The other six amino acid substitutions, encoded by BCHE*37S, BCHE*125F, BCHE*170E, BCHE*471R, and BCHE*518L, seem to cause reduced expression of BChE protein, and their role in determining the silent phenotype was confirmed by expression in cell culture. The other four silent alleles, BCHE*271STOP, BCHE*500STOP, BCHE*FS6, and BCHE*I2E3-8G, encode BChES truncated at their C-terminus because of premature stop codons caused by nucleotide substitutions, a frame shift, or altered splicing. The large number of different silent BCHE alleles found within a relatively small number of patients shows that the heterogeneity of the silent BChE phenotype is high. The characterization of silent BChE variants will be useful in the study of the structure/function relationship for this and other closely related enzymes.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>PMID: 8554068</identifier><identifier>CODEN: AJHGAG</identifier><language>eng</language><publisher>Chicago, IL: University of Chicago Press</publisher><subject>Alleles ; Amino Acid Sequence ; Animals ; Base Sequence ; Biological and medical sciences ; Butyrylcholinesterase - biosynthesis ; Butyrylcholinesterase - blood ; Butyrylcholinesterase - genetics ; Cell Line ; DNA Primers ; Exons ; Female ; Gene Frequency ; General pharmacology ; Hominidae - genetics ; Humans ; Introns ; Kidney ; Kinetics ; Male ; Medical sciences ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Pedigree ; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions ; Pharmacology. Drug treatments ; Phenotype ; Point Mutation ; Polymerase Chain Reaction ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - metabolism ; Sequence Homology, Amino Acid ; Transfection</subject><ispartof>American journal of human genetics, 1996, Vol.58 (1), p.52-64</ispartof><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1914969/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1914969/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3026322$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8554068$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PRIMO-PARMO, S. L</creatorcontrib><creatorcontrib>BARTELS, C. F</creatorcontrib><creatorcontrib>WIERSEMA, B</creatorcontrib><creatorcontrib>VAN DER SPEK, A. F. L</creatorcontrib><creatorcontrib>INNIS, J. W</creatorcontrib><creatorcontrib>LA DU, B. N</creatorcontrib><title>Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>The silent phenotype of human butyrylcholinesterase (BChE), present in most human populations in frequencies of approximately 1/100,000, is characterized by the complete absence of BChE activity or by activity <10% of the average levels of the usual phenotype. Heterogeneity in this phenotype has been well established at the phenotypic level, but only a few silent BCHE alleles have been characterized at the DNA level. Twelve silent alleles of the human butyrylcholinesterase gene (BCHE) have been identified in 17 apparently unrelated patients who were selected by their increased sensitivity to the muscle relaxant succinylcholine. All of these alleles are characterized by single nucleotide substitutions or deletions leading to distinct changes in the structure of the BChE enzyme molecule. Nine of the nucleotide substitutions result in the replacement of single amino acid residues. Three of these variants, BCHE*33C, BCHE*198G, and BCHE*201T, produce normal amounts of immunoreactive but enzymatically inactive BChE protein in the plasma. The other six amino acid substitutions, encoded by BCHE*37S, BCHE*125F, BCHE*170E, BCHE*471R, and BCHE*518L, seem to cause reduced expression of BChE protein, and their role in determining the silent phenotype was confirmed by expression in cell culture. The other four silent alleles, BCHE*271STOP, BCHE*500STOP, BCHE*FS6, and BCHE*I2E3-8G, encode BChES truncated at their C-terminus because of premature stop codons caused by nucleotide substitutions, a frame shift, or altered splicing. The large number of different silent BCHE alleles found within a relatively small number of patients shows that the heterogeneity of the silent BChE phenotype is high. The characterization of silent BChE variants will be useful in the study of the structure/function relationship for this and other closely related enzymes.</description><subject>Alleles</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Butyrylcholinesterase - biosynthesis</subject><subject>Butyrylcholinesterase - blood</subject><subject>Butyrylcholinesterase - genetics</subject><subject>Cell Line</subject><subject>DNA Primers</subject><subject>Exons</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>General pharmacology</subject><subject>Hominidae - genetics</subject><subject>Humans</subject><subject>Introns</subject><subject>Kidney</subject><subject>Kinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Pedigree</subject><subject>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenotype</subject><subject>Point Mutation</subject><subject>Polymerase Chain Reaction</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Recombinant Proteins - metabolism</subject><subject>Sequence Homology, Amino Acid</subject><subject>Transfection</subject><issn>0002-9297</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1Lw0AQhhdRaq3-BCEHET0E9iO73b0IGuoHFLzUc5hsJs3KJqnZRKi_3oih6Glgnnfed2aOyJxJsYyVovKYzCmlPDbcLE_JWQjvlDKmqZiRmZYyoUrPySatoAPbY-e-oHdtE7VlxHgUnMemj8B79Bh-mn2FUTXU0ET50O-7vbdV612DYZyFgNHNQ_q8uo222OA5OSnBB7yY6oK8Pa426XO8fn16Se_X8U5w1sfIgHFWcKWxKHLJbGkBy8Qmsiy5SYRROZicGypQClEanRhdsERqqYTVCGJB7n59d0NeY2HHjTvw2a5zNXT7rAWX_SeNq7Jt-5kxwxKjzGhwPRl07ccwnpLVLlj0Hhpsh5CxJRWaazEKL_8mHSKmP478auIQLPiyg8a6cJAJypXgXHwDcEh9pA</recordid><startdate>1996</startdate><enddate>1996</enddate><creator>PRIMO-PARMO, S. L</creator><creator>BARTELS, C. F</creator><creator>WIERSEMA, B</creator><creator>VAN DER SPEK, A. F. L</creator><creator>INNIS, J. W</creator><creator>LA DU, B. N</creator><general>University of Chicago Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>1996</creationdate><title>Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene</title><author>PRIMO-PARMO, S. L ; BARTELS, C. F ; WIERSEMA, B ; VAN DER SPEK, A. F. L ; INNIS, J. W ; LA DU, B. N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p321t-e1a121d268eddb51cfcaef4c45ff294396ba9b2903e533f98498d1458563c8ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Alleles</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Butyrylcholinesterase - biosynthesis</topic><topic>Butyrylcholinesterase - blood</topic><topic>Butyrylcholinesterase - genetics</topic><topic>Cell Line</topic><topic>DNA Primers</topic><topic>Exons</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>General pharmacology</topic><topic>Hominidae - genetics</topic><topic>Humans</topic><topic>Introns</topic><topic>Kidney</topic><topic>Kinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Pedigree</topic><topic>Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenotype</topic><topic>Point Mutation</topic><topic>Polymerase Chain Reaction</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Recombinant Proteins - metabolism</topic><topic>Sequence Homology, Amino Acid</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PRIMO-PARMO, S. L</creatorcontrib><creatorcontrib>BARTELS, C. F</creatorcontrib><creatorcontrib>WIERSEMA, B</creatorcontrib><creatorcontrib>VAN DER SPEK, A. F. L</creatorcontrib><creatorcontrib>INNIS, J. W</creatorcontrib><creatorcontrib>LA DU, B. N</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PRIMO-PARMO, S. L</au><au>BARTELS, C. F</au><au>WIERSEMA, B</au><au>VAN DER SPEK, A. F. L</au><au>INNIS, J. W</au><au>LA DU, B. N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene</atitle><jtitle>American journal of human genetics</jtitle><addtitle>Am J Hum Genet</addtitle><date>1996</date><risdate>1996</risdate><volume>58</volume><issue>1</issue><spage>52</spage><epage>64</epage><pages>52-64</pages><issn>0002-9297</issn><eissn>1537-6605</eissn><coden>AJHGAG</coden><abstract>The silent phenotype of human butyrylcholinesterase (BChE), present in most human populations in frequencies of approximately 1/100,000, is characterized by the complete absence of BChE activity or by activity <10% of the average levels of the usual phenotype. Heterogeneity in this phenotype has been well established at the phenotypic level, but only a few silent BCHE alleles have been characterized at the DNA level. Twelve silent alleles of the human butyrylcholinesterase gene (BCHE) have been identified in 17 apparently unrelated patients who were selected by their increased sensitivity to the muscle relaxant succinylcholine. All of these alleles are characterized by single nucleotide substitutions or deletions leading to distinct changes in the structure of the BChE enzyme molecule. Nine of the nucleotide substitutions result in the replacement of single amino acid residues. Three of these variants, BCHE*33C, BCHE*198G, and BCHE*201T, produce normal amounts of immunoreactive but enzymatically inactive BChE protein in the plasma. The other six amino acid substitutions, encoded by BCHE*37S, BCHE*125F, BCHE*170E, BCHE*471R, and BCHE*518L, seem to cause reduced expression of BChE protein, and their role in determining the silent phenotype was confirmed by expression in cell culture. The other four silent alleles, BCHE*271STOP, BCHE*500STOP, BCHE*FS6, and BCHE*I2E3-8G, encode BChES truncated at their C-terminus because of premature stop codons caused by nucleotide substitutions, a frame shift, or altered splicing. The large number of different silent BCHE alleles found within a relatively small number of patients shows that the heterogeneity of the silent BChE phenotype is high. The characterization of silent BChE variants will be useful in the study of the structure/function relationship for this and other closely related enzymes.</abstract><cop>Chicago, IL</cop><pub>University of Chicago Press</pub><pmid>8554068</pmid><tpages>13</tpages></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Alleles Amino Acid Sequence Animals Base Sequence Biological and medical sciences Butyrylcholinesterase - biosynthesis Butyrylcholinesterase - blood Butyrylcholinesterase - genetics Cell Line DNA Primers Exons Female Gene Frequency General pharmacology Hominidae - genetics Humans Introns Kidney Kinetics Male Medical sciences Molecular Sequence Data Mutagenesis, Site-Directed Pedigree Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions Pharmacology. Drug treatments Phenotype Point Mutation Polymerase Chain Reaction Recombinant Proteins - biosynthesis Recombinant Proteins - metabolism Sequence Homology, Amino Acid Transfection |
| title | Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene |
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