A digenic cause of cleft lip in A-strain mice and definition of candidate genes for the two loci
BACKGROUND Nonsyndromic cleft lip with or without cleft palate, CL(P), is a common human birth defect with a complex unknown genetic cause. The mouse model is the “A/∼” strains. Our previous studies mapped two loci: clf1 on Chr11 and clf2 on Chr13—with a strong genetic maternal effect on the level o...
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| Veröffentlicht in: | Birth defects research. A Clinical and molecular teratology 2004-08, Vol.70 (8), p.509-518 |
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| creator | Juriloff, Diana M. Harris, Muriel J. Dewell, Sarah L. |
| description | BACKGROUND
Nonsyndromic cleft lip with or without cleft palate, CL(P), is a common human birth defect with a complex unknown genetic cause. The mouse model is the “A/∼” strains. Our previous studies mapped two loci: clf1 on Chr11 and clf2 on Chr13—with a strong genetic maternal effect on the level of risk. Here we test the hypothesis that CL(P) is digenic and identify candidate genes for clf1 and clf2.
METHODS
We observed E14 CL(P) frequencies in backcross (BC1) embryos from a new cross of A/WySn to AXB‐4/Pgn and from test crosses of three new “congenic RI” lines. Using new polymorphic markers from genes and our mapping panels of segregants and RI strains, we identified the candidate genes for clf1 and clf2. We sequenced the coding region of Ptch in A/WySn cDNA.
RESULTS
Seventy new BC1 CL(P) segregants (4%) were obtained, as predicted. All three new congenic RI lines homozygous for both clf1 and clf2 had A/WySn‐level CL(P) frequencies (10–30%) in test crosses. The clf1 region contains 10 known genes (Arf2, Cdc27, Crhr1, Gosr2, Itgb3, Mapt, Myl4, Nsf, Wnt3, and Wnt9b). The clf2 region contains 17 known genes with human orthologs. Both regions contain additional potential genes. No causal mutation in Ptch coding sequence was found.
CONCLUSIONS
In A‐strain mice, nonsyndromic CL(P) is digenic, suggesting that nonsyndromic human CL(P) may also be digenic. The orthologous human genes are on 17q (clf1) and 9q, 8q and 5p (clf2), and good candidate genes are WNT3 or WNT9B (17q), and PTCH (9q) or MTRR (5p). Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/bdra.20041 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66818384</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66818384</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4901-f9ffe8cb931e85f527768e14e390290595752fe784f19889b87f72508a60a4ee3</originalsourceid><addsrcrecordid>eNqF0EtPGzEQB3CrAhVIe-EDVL7QA9JSP9avY5LykqJWqqg4uo53TN1udoO9UeDbY0iAG5w8sn4zo_kjdEjJCSWEfZs3yZ0wQmr6Ae1TUbOKKEl2XmrB9tBBzv-K5Uqpj2iPCs6MZnof_RnjJt5AFz32bpUB9wH7FsKA27jEscPjKg_JlWIRPWDXNbiBELs4xL57wuUrNm4AXKZAxqFPePgLeFj3uO19_IR2g2szfN6-I_T77PRqelHNfp5fTsezyteG0CqYEED7ueEUtAiCKSU10Bq4IcwQYUQ5I4DSdaBGazPXKigmiHaSuBqAj9DXzdxl6m9XkAe7iNlD27oO-lW2Umqqua7fhVRJySVXBR5voE99zgmCXaa4cOneUmIfg7ePwdun4Av-sp26mi-geaXbpAs42gKXvWtDcp2P-dVJypiWpji6cevYwv0bK-3k-6_x8_Jq0xPzAHcvPS79t1JxJez1j3M7Ke1XcnJtp_wBCTOnNg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17663637</pqid></control><display><type>article</type><title>A digenic cause of cleft lip in A-strain mice and definition of candidate genes for the two loci</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Juriloff, Diana M. ; Harris, Muriel J. ; Dewell, Sarah L.</creator><creatorcontrib>Juriloff, Diana M. ; Harris, Muriel J. ; Dewell, Sarah L.</creatorcontrib><description>BACKGROUND
Nonsyndromic cleft lip with or without cleft palate, CL(P), is a common human birth defect with a complex unknown genetic cause. The mouse model is the “A/∼” strains. Our previous studies mapped two loci: clf1 on Chr11 and clf2 on Chr13—with a strong genetic maternal effect on the level of risk. Here we test the hypothesis that CL(P) is digenic and identify candidate genes for clf1 and clf2.
METHODS
We observed E14 CL(P) frequencies in backcross (BC1) embryos from a new cross of A/WySn to AXB‐4/Pgn and from test crosses of three new “congenic RI” lines. Using new polymorphic markers from genes and our mapping panels of segregants and RI strains, we identified the candidate genes for clf1 and clf2. We sequenced the coding region of Ptch in A/WySn cDNA.
RESULTS
Seventy new BC1 CL(P) segregants (4%) were obtained, as predicted. All three new congenic RI lines homozygous for both clf1 and clf2 had A/WySn‐level CL(P) frequencies (10–30%) in test crosses. The clf1 region contains 10 known genes (Arf2, Cdc27, Crhr1, Gosr2, Itgb3, Mapt, Myl4, Nsf, Wnt3, and Wnt9b). The clf2 region contains 17 known genes with human orthologs. Both regions contain additional potential genes. No causal mutation in Ptch coding sequence was found.
CONCLUSIONS
In A‐strain mice, nonsyndromic CL(P) is digenic, suggesting that nonsyndromic human CL(P) may also be digenic. The orthologous human genes are on 17q (clf1) and 9q, 8q and 5p (clf2), and good candidate genes are WNT3 or WNT9B (17q), and PTCH (9q) or MTRR (5p). Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 1542-0752</identifier><identifier>EISSN: 1542-0760</identifier><identifier>DOI: 10.1002/bdra.20041</identifier><identifier>PMID: 15329828</identifier><identifier>CODEN: BDRPBT</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Base Sequence ; Biological and medical sciences ; Chromosome Mapping ; cleft lip ; Cleft Lip - genetics ; cleft palate ; congenic ; Crosses, Genetic ; digenic ; Disease Models, Animal ; DNA Primers ; Embryology: invertebrates and vertebrates. Teratology ; Female ; Fundamental and applied biological sciences. Psychology ; Male ; Mice ; Mice, Inbred A - genetics ; Mice, Inbred C57BL - genetics ; mouse ; multifactorial ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Teratology. Teratogens</subject><ispartof>Birth defects research. A Clinical and molecular teratology, 2004-08, Vol.70 (8), p.509-518</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4901-f9ffe8cb931e85f527768e14e390290595752fe784f19889b87f72508a60a4ee3</citedby><cites>FETCH-LOGICAL-c4901-f9ffe8cb931e85f527768e14e390290595752fe784f19889b87f72508a60a4ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbdra.20041$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbdra.20041$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16122869$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15329828$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Juriloff, Diana M.</creatorcontrib><creatorcontrib>Harris, Muriel J.</creatorcontrib><creatorcontrib>Dewell, Sarah L.</creatorcontrib><title>A digenic cause of cleft lip in A-strain mice and definition of candidate genes for the two loci</title><title>Birth defects research. A Clinical and molecular teratology</title><addtitle>Birth Defects Research Part A: Clinical and Molecular Teratology</addtitle><description>BACKGROUND
Nonsyndromic cleft lip with or without cleft palate, CL(P), is a common human birth defect with a complex unknown genetic cause. The mouse model is the “A/∼” strains. Our previous studies mapped two loci: clf1 on Chr11 and clf2 on Chr13—with a strong genetic maternal effect on the level of risk. Here we test the hypothesis that CL(P) is digenic and identify candidate genes for clf1 and clf2.
METHODS
We observed E14 CL(P) frequencies in backcross (BC1) embryos from a new cross of A/WySn to AXB‐4/Pgn and from test crosses of three new “congenic RI” lines. Using new polymorphic markers from genes and our mapping panels of segregants and RI strains, we identified the candidate genes for clf1 and clf2. We sequenced the coding region of Ptch in A/WySn cDNA.
RESULTS
Seventy new BC1 CL(P) segregants (4%) were obtained, as predicted. All three new congenic RI lines homozygous for both clf1 and clf2 had A/WySn‐level CL(P) frequencies (10–30%) in test crosses. The clf1 region contains 10 known genes (Arf2, Cdc27, Crhr1, Gosr2, Itgb3, Mapt, Myl4, Nsf, Wnt3, and Wnt9b). The clf2 region contains 17 known genes with human orthologs. Both regions contain additional potential genes. No causal mutation in Ptch coding sequence was found.
CONCLUSIONS
In A‐strain mice, nonsyndromic CL(P) is digenic, suggesting that nonsyndromic human CL(P) may also be digenic. The orthologous human genes are on 17q (clf1) and 9q, 8q and 5p (clf2), and good candidate genes are WNT3 or WNT9B (17q), and PTCH (9q) or MTRR (5p). Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Chromosome Mapping</subject><subject>cleft lip</subject><subject>Cleft Lip - genetics</subject><subject>cleft palate</subject><subject>congenic</subject><subject>Crosses, Genetic</subject><subject>digenic</subject><subject>Disease Models, Animal</subject><subject>DNA Primers</subject><subject>Embryology: invertebrates and vertebrates. Teratology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred A - genetics</subject><subject>Mice, Inbred C57BL - genetics</subject><subject>mouse</subject><subject>multifactorial</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic</subject><subject>Teratology. Teratogens</subject><issn>1542-0752</issn><issn>1542-0760</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0EtPGzEQB3CrAhVIe-EDVL7QA9JSP9avY5LykqJWqqg4uo53TN1udoO9UeDbY0iAG5w8sn4zo_kjdEjJCSWEfZs3yZ0wQmr6Ae1TUbOKKEl2XmrB9tBBzv-K5Uqpj2iPCs6MZnof_RnjJt5AFz32bpUB9wH7FsKA27jEscPjKg_JlWIRPWDXNbiBELs4xL57wuUrNm4AXKZAxqFPePgLeFj3uO19_IR2g2szfN6-I_T77PRqelHNfp5fTsezyteG0CqYEED7ueEUtAiCKSU10Bq4IcwQYUQ5I4DSdaBGazPXKigmiHaSuBqAj9DXzdxl6m9XkAe7iNlD27oO-lW2Umqqua7fhVRJySVXBR5voE99zgmCXaa4cOneUmIfg7ePwdun4Av-sp26mi-geaXbpAs42gKXvWtDcp2P-dVJypiWpji6cevYwv0bK-3k-6_x8_Jq0xPzAHcvPS79t1JxJez1j3M7Ke1XcnJtp_wBCTOnNg</recordid><startdate>200408</startdate><enddate>200408</enddate><creator>Juriloff, Diana M.</creator><creator>Harris, Muriel J.</creator><creator>Dewell, Sarah L.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>BSCLL</scope><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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200408</creationdate><title>A digenic cause of cleft lip in A-strain mice and definition of candidate genes for the two loci</title><author>Juriloff, Diana M. ; Harris, Muriel J. ; Dewell, Sarah L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4901-f9ffe8cb931e85f527768e14e390290595752fe784f19889b87f72508a60a4ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Chromosome Mapping</topic><topic>cleft lip</topic><topic>Cleft Lip - genetics</topic><topic>cleft palate</topic><topic>congenic</topic><topic>Crosses, Genetic</topic><topic>digenic</topic><topic>Disease Models, Animal</topic><topic>DNA Primers</topic><topic>Embryology: invertebrates and vertebrates. Teratology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred A - genetics</topic><topic>Mice, Inbred C57BL - genetics</topic><topic>mouse</topic><topic>multifactorial</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic</topic><topic>Teratology. Teratogens</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Juriloff, Diana M.</creatorcontrib><creatorcontrib>Harris, Muriel J.</creatorcontrib><creatorcontrib>Dewell, Sarah L.</creatorcontrib><collection>Istex</collection><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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Birth defects research. A Clinical and molecular teratology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Juriloff, Diana M.</au><au>Harris, Muriel J.</au><au>Dewell, Sarah L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A digenic cause of cleft lip in A-strain mice and definition of candidate genes for the two loci</atitle><jtitle>Birth defects research. A Clinical and molecular teratology</jtitle><addtitle>Birth Defects Research Part A: Clinical and Molecular Teratology</addtitle><date>2004-08</date><risdate>2004</risdate><volume>70</volume><issue>8</issue><spage>509</spage><epage>518</epage><pages>509-518</pages><issn>1542-0752</issn><eissn>1542-0760</eissn><coden>BDRPBT</coden><abstract>BACKGROUND
Nonsyndromic cleft lip with or without cleft palate, CL(P), is a common human birth defect with a complex unknown genetic cause. The mouse model is the “A/∼” strains. Our previous studies mapped two loci: clf1 on Chr11 and clf2 on Chr13—with a strong genetic maternal effect on the level of risk. Here we test the hypothesis that CL(P) is digenic and identify candidate genes for clf1 and clf2.
METHODS
We observed E14 CL(P) frequencies in backcross (BC1) embryos from a new cross of A/WySn to AXB‐4/Pgn and from test crosses of three new “congenic RI” lines. Using new polymorphic markers from genes and our mapping panels of segregants and RI strains, we identified the candidate genes for clf1 and clf2. We sequenced the coding region of Ptch in A/WySn cDNA.
RESULTS
Seventy new BC1 CL(P) segregants (4%) were obtained, as predicted. All three new congenic RI lines homozygous for both clf1 and clf2 had A/WySn‐level CL(P) frequencies (10–30%) in test crosses. The clf1 region contains 10 known genes (Arf2, Cdc27, Crhr1, Gosr2, Itgb3, Mapt, Myl4, Nsf, Wnt3, and Wnt9b). The clf2 region contains 17 known genes with human orthologs. Both regions contain additional potential genes. No causal mutation in Ptch coding sequence was found.
CONCLUSIONS
In A‐strain mice, nonsyndromic CL(P) is digenic, suggesting that nonsyndromic human CL(P) may also be digenic. The orthologous human genes are on 17q (clf1) and 9q, 8q and 5p (clf2), and good candidate genes are WNT3 or WNT9B (17q), and PTCH (9q) or MTRR (5p). Birth Defects Research (Part A), 2004. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15329828</pmid><doi>10.1002/bdra.20041</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Base Sequence Biological and medical sciences Chromosome Mapping cleft lip Cleft Lip - genetics cleft palate congenic Crosses, Genetic digenic Disease Models, Animal DNA Primers Embryology: invertebrates and vertebrates. Teratology Female Fundamental and applied biological sciences. Psychology Male Mice Mice, Inbred A - genetics Mice, Inbred C57BL - genetics mouse multifactorial Polymerase Chain Reaction Polymorphism, Genetic Teratology. Teratogens |
| title | A digenic cause of cleft lip in A-strain mice and definition of candidate genes for the two loci |
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