{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T07:10:12Z","timestamp":1723792212497},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,8,8]],"date-time":"2003-08-08T00:00:00Z","timestamp":1060300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Abnormally low concentrations of brain gamma\u2010aminobutyric acid (GABA) have been reported in unipolar depression. Almost all of the brain GABA is synthesized by glutamate decarboxylase (GAD) enzymes (GAD67 and GAD65). These enzymes, therefore, play a central role in brain GABA homeostasis. We screened all the 17 exons of the <jats:italic>GAD67<\/jats:italic> gene for mutations using single strand conformation polymorphism (SSCP) or denaturing high pressure liquid chromatography (dHPLC) in a sample of 43 individuals diagnosed with major unipolar depression or other disorders with putative GABAergic dysfunction. We identified eight novel variants (five synonymous base substitutions, two insertion\/deletions and one tandem repeat). Three relatively common (minor allele frequency &gt;20%) single nucleotide polymorphisms (SNPs), located in the 5\u2032 non\u2010coding region (exon 0), intron 8, and the 3\u2032 non\u2010coding region (exon 16) of the gene, were genotyped in 103 European\u2010American (EA) subjects with depression and 125 EA psychiatrically screened controls. Linkage disequilibrium (LD) and haplotype frequencies were estimated using the 3LOCUS program. Significant LD was observed between the intron 8 SNP and the exon 16 SNP and between the exon 0 SNP and the exon 16 SNP. Three common GAD67 haplotypes were observed in this population, which accounted for &gt;90% of the possible GAD67 three\u2010locus haplotypes. Comparison of SNP and haplotype frequencies between individuals with depression and controls revealed no differences. These results demonstrate a significant within\u2010gene LD for <jats:italic>GAD67<\/jats:italic> in the EA population and begin to establish a haplotype map for this gene. Furthermore, these results suggest that common genetic variation within the <jats:italic>GAD67<\/jats:italic> gene does not play a major role in the predisposition to unipolar depression. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.20055","type":"journal-article","created":{"date-parts":[[2003,12,15]],"date-time":"2003-12-15T08:01:06Z","timestamp":1071475266000},"page":"81-86","source":"Crossref","is-referenced-by-count":14,"title":["Mutation screen of the glutamate decarboxylase\u201067 gene and haplotype association to unipolar depression"],"prefix":"10.1002","volume":"124B","author":[{"given":"Jaakko","family":"Lappalainen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Sanacora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry R.","family":"Kranzler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Malison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen S.","family":"Hibbard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence H.","family":"Price","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Krystal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Gelernter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,8,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90863-X"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90200-5"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1898"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.12.6496"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(88)90024-8"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(88)90156-6"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1246"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.6.2115"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-229"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.19.10483"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1978.01770310043002"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.138.8.1098"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1042"},{"key":"e_1_2_5_15_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/genetics\/49.1.49","article-title":"The interaction of selection and linkage. 1. 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