| http://purl.uniprot.org/citations/21282601 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21282601 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21282601 | http://www.w3.org/2000/01/rdf-schema#comment | "Dominant human genetic diseases that impair reproductive fitness and have high locus heterogeneity constitute a problem for gene discovery because the usual criterion of finding more mutations in specific genes than expected by chance may require extremely large populations. Heterotaxy (Htx), a congenital heart disease resulting from abnormalities in left-right (LR) body patterning, has features suggesting that many cases fall into this category. In this setting, appropriate model systems may provide a means to support implication of specific genes. By high-resolution genotyping of 262 Htx subjects and 991 controls, we identify a twofold excess of subjects with rare genic copy number variations in Htx (14.5% vs. 7.4%, P = 1.5 × 10(-4)). Although 7 of 45 Htx copy number variations were large chromosomal abnormalities, 38 smaller copy number variations altered a total of 61 genes, 22 of which had Xenopus orthologs. In situ hybridization identified 7 of these 22 genes with expression in the ciliated LR organizer (gastrocoel roof plate), a marked enrichment compared with 40 of 845 previously studied genes (sevenfold enrichment, P < 10(-6)). Morpholino knockdown in Xenopus of Htx candidates demonstrated that five (NEK2, ROCK2, TGFBR2, GALNT11, and NUP188) strongly disrupted both morphological LR development and expression of pitx2, a molecular marker of LR patterning. These effects were specific, because 0 of 13 control genes from rare Htx or control copy number variations produced significant LR abnormalities (P = 0.001). These findings identify genes not previously implicated in LR patterning."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1019645108"xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1019645108"xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Lifton R.P."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Lifton R.P."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Brueckner M."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Brueckner M."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Choi M."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Choi M."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Towbin J.A."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Towbin J.A."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Khokha M.K."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Khokha M.K."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Belmont J.W."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Belmont J.W."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Ware S.M."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Ware S.M."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Fakhro K.A."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/author | "Fakhro K.A."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
| http://purl.uniprot.org/citations/21282601 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |