Genomic organization of ATOX1, a human copper chaperone
<p>Abstract</p> <p>Background</p> <p>Copper is an essential trace element that plays a critical role in the survival of all living organisms. Menkes disease and occipital horn syndrome (OHS) are allelic disorders of copper transport caused by defects in a X-linked gene...
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| Format: | Article |
| Language: | English |
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BMC
2003-02-01
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| Series: | BMC Genetics |
| Online Access: | http://www.biomedcentral.com/1471-2156/4/4 |
| _version_ | 1811290981016797184 |
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| author | Kaler Stephen G Koeller David M Liu Po-Ching |
| author_facet | Kaler Stephen G Koeller David M Liu Po-Ching |
| author_sort | Kaler Stephen G |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Copper is an essential trace element that plays a critical role in the survival of all living organisms. Menkes disease and occipital horn syndrome (OHS) are allelic disorders of copper transport caused by defects in a X-linked gene (ATP7A) that encodes a P-type ATPase that transports copper across cellular membranes, including the <it>trans-Golgi </it>network. Genetic studies in yeast recently revealed a new family of cytoplasmic proteins called copper chaperones which bind copper ions and deliver them to specific cellular pathways. Biochemical studies of the human homolog of one copper chaperone, ATOX1, indicate direct interaction with the Menkes/OHS protein. Although no disease-associated mutations have been reported in ATOX1, mice with disruption of the ATOX1 locus demonstrate perinatal mortality similar to that observed in the <it>brindled </it>mice (<it>Mo</it><sup>br</sup>), a mouse model of Menkes disease. The cDNA sequence for ATOX1 is known, and the genomic organization has not been reported.</p> <p>Results</p> <p>We determined the genomic structure of ATOX1. The gene contains 4 exons spanning a genomic distance of approximately 16 kb. The translation start codon is located in the 3' end of exon 1 and the termination codon in exon 3. We developed a PCR-based assay to amplify the coding regions and splice junctions from genomic DNA. We screened for ATOX1 mutations in two patients with classical Menkes disease phenotypes and one individual with occipital horn syndrome who had no alterations detected in ATP7A, as well as an adult female with chronic anemia, low serum copper and evidence of mild dopamine-beta-hydroxylase deficiency and no alterations in the ATOX1 coding or splice junction sequences were found.</p> <p>Conclusions</p> <p>In this study, we characterized the genomic structure of the human copper chaperone ATOX1 to facilitate screening of this gene from genomic DNA in patients whose clinical or biochemical phenotypes suggest impaired copper transport.</p> |
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| institution | Directory Open Access Journal |
| issn | 1471-2156 |
| language | English |
| last_indexed | 2024-04-13T04:22:32Z |
| publishDate | 2003-02-01 |
| publisher | BMC |
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| series | BMC Genetics |
| spelling | doaj.art-d6bf91c4d62a4eddb49cd0cd3fe6c4fd2022-12-22T03:02:41ZengBMCBMC Genetics1471-21562003-02-0141410.1186/1471-2156-4-4Genomic organization of ATOX1, a human copper chaperoneKaler Stephen GKoeller David MLiu Po-Ching<p>Abstract</p> <p>Background</p> <p>Copper is an essential trace element that plays a critical role in the survival of all living organisms. Menkes disease and occipital horn syndrome (OHS) are allelic disorders of copper transport caused by defects in a X-linked gene (ATP7A) that encodes a P-type ATPase that transports copper across cellular membranes, including the <it>trans-Golgi </it>network. Genetic studies in yeast recently revealed a new family of cytoplasmic proteins called copper chaperones which bind copper ions and deliver them to specific cellular pathways. Biochemical studies of the human homolog of one copper chaperone, ATOX1, indicate direct interaction with the Menkes/OHS protein. Although no disease-associated mutations have been reported in ATOX1, mice with disruption of the ATOX1 locus demonstrate perinatal mortality similar to that observed in the <it>brindled </it>mice (<it>Mo</it><sup>br</sup>), a mouse model of Menkes disease. The cDNA sequence for ATOX1 is known, and the genomic organization has not been reported.</p> <p>Results</p> <p>We determined the genomic structure of ATOX1. The gene contains 4 exons spanning a genomic distance of approximately 16 kb. The translation start codon is located in the 3' end of exon 1 and the termination codon in exon 3. We developed a PCR-based assay to amplify the coding regions and splice junctions from genomic DNA. We screened for ATOX1 mutations in two patients with classical Menkes disease phenotypes and one individual with occipital horn syndrome who had no alterations detected in ATP7A, as well as an adult female with chronic anemia, low serum copper and evidence of mild dopamine-beta-hydroxylase deficiency and no alterations in the ATOX1 coding or splice junction sequences were found.</p> <p>Conclusions</p> <p>In this study, we characterized the genomic structure of the human copper chaperone ATOX1 to facilitate screening of this gene from genomic DNA in patients whose clinical or biochemical phenotypes suggest impaired copper transport.</p>http://www.biomedcentral.com/1471-2156/4/4 |
| spellingShingle | Kaler Stephen G Koeller David M Liu Po-Ching Genomic organization of ATOX1, a human copper chaperone BMC Genetics |
| title | Genomic organization of ATOX1, a human copper chaperone |
| title_full | Genomic organization of ATOX1, a human copper chaperone |
| title_fullStr | Genomic organization of ATOX1, a human copper chaperone |
| title_full_unstemmed | Genomic organization of ATOX1, a human copper chaperone |
| title_short | Genomic organization of ATOX1, a human copper chaperone |
| title_sort | genomic organization of atox1 a human copper chaperone |
| url | http://www.biomedcentral.com/1471-2156/4/4 |
| work_keys_str_mv | AT kalerstepheng genomicorganizationofatox1ahumancopperchaperone AT koellerdavidm genomicorganizationofatox1ahumancopperchaperone AT liupoching genomicorganizationofatox1ahumancopperchaperone |