The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

PDHA1  -  pyruvate dehydrogenase (lipoamide) alpha 1

Homo sapiens

 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of PDHA1

  • In a patient with fatal neonatal lactic acidosis due to pyruvate dehydrogenase deficiency, the only potential mutation detected was c.888C>G in PDHA1, the gene for the E1alpha subunit of the complex [1].
 

High impact information on PDHA1

  • The mutation was a base substitution of G by C at nucleotide 134 in the mitochondrial targeting sequence of the PDHA1 gene, resulting in an arginine-to-proline substitution at codon 10 (R10P) [2].
  • A four-nucleotide insertion hotspot in the X chromosome located pyruvate dehydrogenase E1 alpha gene (PDHA1) [3].
  • Nucleotide diversity at FIX is the lowest among the existing non-Y chromosome nuclear gene datasets and is less than 10% of the diversity found at PDHA1 [4].
  • An explicit comparison is made with another X-linked gene, PDHA1, for which the sampling of individuals was very similar [4].
  • Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency [5].
 

Biological context of PDHA1

 

Anatomical context of PDHA1

  • PDHA1 cDNA from cultured fibroblasts revealed two populations, one normal, the other lacking exon 6 (c.511-603 del) [10].
  • However, PDC activity was within the normal range in lymphocytes and the direct sequencing of the 11 exons and intron-exon junctions of the PDHA 1 gene did not show any changes [11].
 

Associations of PDHA1 with chemical compounds

  • However, the great majority of PDH complex deficiencies result from mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) [5].
  • Nuclear run-on assays and promoter analysis indicate that the glucose-induced increases in the levels of E1alpha mRNA in HepG2 cells are due to increased transcription of the human E1alpha (PDHA1) gene [12].
  • Sequencing analysis of PDHA1 gene of the patient revealed a substitution of cysteine for tyrosine at position 161 (Y161C) [13].
  • A pathogenic glutamate-to-aspartate substitution (D296E) in the pyruvate dehydrogenase E1 subunit gene PDHA1 [1].
  • A Korean Female Patient with Thiamine-responsive Pyruvate Dehydrogenase Complex Deficiency Due to a Novel Point Mutation (Y161C)in the PDHA1 Gene [13].
 

Other interactions of PDHA1

  • 1. In addition to establishing the order of PDHA1, ISPK-1, DXS2504, DXS1528 and the 13 known polymorphic loci as Xpter-PDHA1-DXS443-DXS3424-ISPK-1-DXS12 29-DXS2504-DXS1528-DXS365-DXS7101- DXS1683-DXS1052-DXS274-DXS92-DXS1226-DX S41-DXS989-DXS451-Xcen, we have also developed 35 novel STSs from YAC end clones [9].
  • Two individuals with pyruvate dehydrogenase (PDH) deficiency due to missense mutations in the gene for the E1alpha subunit (PDHA1) presented during childhood with dystonia [14].
  • The gene located on chromosome X (PDHA-1) is expressed in somatic tissues, whereas the second gene (PDHA-2), located on chromosome 4, is expressed only in post-meiotic spermatogenic cells [15].
 

Analytical, diagnostic and therapeutic context of PDHA1

References

  1. A pathogenic glutamate-to-aspartate substitution (D296E) in the pyruvate dehydrogenase E1 subunit gene PDHA1. Brown, R.M., Head, R.A., Boubriak, I.I., Leonard, J.V., Brown, G.K. Hum. Mutat. (2003) [Pubmed]
  2. An amino acid substitution in the pyruvate dehydrogenase E1 alpha gene, affecting mitochondrial import of the precursor protein. Takakubo, F., Cartwright, P., Hoogenraad, N., Thorburn, D.R., Collins, F., Lithgow, T., Dahl, H.H. Am. J. Hum. Genet. (1995) [Pubmed]
  3. A four-nucleotide insertion hotspot in the X chromosome located pyruvate dehydrogenase E1 alpha gene (PDHA1). Takakubo, F., Thorburn, D.R., Dahl, H.H. Hum. Mol. Genet. (1993) [Pubmed]
  4. Human populations show reduced DNA sequence variation at the factor IX locus. Harris, E.E., Hey, J. Curr. Biol. (2001) [Pubmed]
  5. Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency. Lissens, W., De Meirleir, L., Seneca, S., Liebaers, I., Brown, G.K., Brown, R.M., Ito, M., Naito, E., Kuroda, Y., Kerr, D.S., Wexler, I.D., Patel, M.S., Robinson, B.H., Seyda, A. Hum. Mutat. (2000) [Pubmed]
  6. Pyruvate dehydrogenase E3 binding protein (protein X) deficiency. Brown, R.M., Head, R.A., Morris, A.A., Raiman, J.A., Walter, J.H., Whitehouse, W.P., Brown, G.K. Developmental medicine and child neurology. (2006) [Pubmed]
  7. A eutherian X-linked gene, PDHA1, is autosomal in marsupials: a model for the evolution of a second, testis-specific variant in eutherian mammals. Fitzgerald, J., Wilcox, S.A., Graves, J.A., Dahl, H.H. Genomics (1993) [Pubmed]
  8. A testis-specific form of the human pyruvate dehydrogenase E1 alpha subunit is coded for by an intronless gene on chromosome 4. Dahl, H.H., Brown, R.M., Hutchison, W.M., Maragos, C., Brown, G.K. Genomics (1990) [Pubmed]
  9. Construction of a YAC contig and an STS map spanning 3.6 megabase pairs in Xp22.1. Trump, D., Pilia, G., Dixon, P.H., Wooding, C., Thakrar, R., Leigh, S.E., Nagaraja, R., Whyte, M.P., Schlessinger, D., Thakker, R.V. Hum. Genet. (1996) [Pubmed]
  10. Somatic mosaicism in a male with an exon skipping mutation in PDHA1 of the pyruvate dehydrogenase complex results in a milder phenotype. Okajima, K., Warman, M.L., Byrne, L.C., Kerr, D.S. Mol. Genet. Metab. (2006) [Pubmed]
  11. First characterization of a large deletion of the PDHA 1 gene. Brivet, M., Moutard, M.L., Zater, M., Venet, L., Chenel, C., Mine, M., Legrand, A. Mol. Genet. Metab. (2005) [Pubmed]
  12. Regulation of mammalian pyruvate dehydrogenase alpha subunit gene expression by glucose in HepG2 cells. Tan, J., Yang, H.S., Patel, M.S. Biochem. J. (1998) [Pubmed]
  13. A Korean Female Patient with Thiamine-responsive Pyruvate Dehydrogenase Complex Deficiency Due to a Novel Point Mutation (Y161C)in the PDHA1 Gene. Lee, E.H., Ahn, M.S., Hwang, J.S., Ryu, K.H., Kim, S.J., Kim, S.H. J. Korean Med. Sci. (2006) [Pubmed]
  14. Pyruvate dehydrogenase deficiency presenting as dystonia in childhood. Head, R.A., de Goede, C.G., Newton, R.W., Walter, J.H., McShane, M.A., Brown, R.M., Brown, G.K. Developmental medicine and child neurology. (2004) [Pubmed]
  15. Characterization of the regulatory region of the human testis-specific form of the pyruvate dehydrogenase alpha-subunit (PDHA-2) gene. Datta, U., Wexler, I.D., Kerr, D.S., Raz, I., Patel, M.S. Biochim. Biophys. Acta (1999) [Pubmed]
 
WikiGenes - Universities