skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: The human B22 subunit of the NADH-ubiquinone oxidoreductase maps to the region of chromosome 8 involved in Branchio-oto-renal syndrome

Abstract

To identify candidate genes for Branchio-oto-renal (BOR) syndrome, we have made use of a set of cosmids that map to 8q13.3, which has previously been shown to be involved in this syndrome. These cosmids were used as genomic clones in the attempts to isolate corresponding cDNAs using a modified hybrid selection technique. cDNAs using a modified hybrid selection technique. cDNAs from the region were identified and used to search for sequence similarity in human or other species. One cDNA clone was found to have 89% sequence similarity to the bovine B22 subunit of NADH-ubiquinone oxidoreductase, a mitochondrial protein in the respiratory electron transport chain. Given the history of other mitochondrial mutations being involved in hearing loss syndromes, this gene should be considered a strong candidate for involvement in BOR.

Authors:
; ;  [1]
  1. Univ. of Houston, TX (United States)
Publication Date:
OSTI Identifier:
466012
Resource Type:
Journal Article
Resource Relation:
Journal Name: Genomics; Journal Volume: 35; Journal Issue: 1; Other Information: PBD: 1 Jul 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; HUMAN CHROMOSOME 8; GENETIC MAPPING; CHROMOSOMAL ABERRATIONS; PATIENTS; HEREDITARY DISEASES; SENSE ORGANS DISEASES; OXIDOREDUCTASES; DNA-CLONING; DNA SEQUENCING; GENE REGULATION; GENE MUTATIONS; MITOCHONDRIA; BIOLOGICAL MARKERS; DOMINANT MUTATIONS; NUCLEOTIDES; UBIQUINONE; COENZYMES; CONTIGS; COSMIDS; HYBRIDIZATION; PROTEINS; POLYMERASE CHAIN REACTION

Citation Formats

Gu, J.Z., Lin, Xin, and Wells, D.E. The human B22 subunit of the NADH-ubiquinone oxidoreductase maps to the region of chromosome 8 involved in Branchio-oto-renal syndrome. United States: N. p., 1996. Web. doi:10.1006/geno.1996.0316.
Gu, J.Z., Lin, Xin, & Wells, D.E. The human B22 subunit of the NADH-ubiquinone oxidoreductase maps to the region of chromosome 8 involved in Branchio-oto-renal syndrome. United States. doi:10.1006/geno.1996.0316.
Gu, J.Z., Lin, Xin, and Wells, D.E. 1996. "The human B22 subunit of the NADH-ubiquinone oxidoreductase maps to the region of chromosome 8 involved in Branchio-oto-renal syndrome". United States. doi:10.1006/geno.1996.0316.
@article{osti_466012,
title = {The human B22 subunit of the NADH-ubiquinone oxidoreductase maps to the region of chromosome 8 involved in Branchio-oto-renal syndrome},
author = {Gu, J.Z. and Lin, Xin and Wells, D.E.},
abstractNote = {To identify candidate genes for Branchio-oto-renal (BOR) syndrome, we have made use of a set of cosmids that map to 8q13.3, which has previously been shown to be involved in this syndrome. These cosmids were used as genomic clones in the attempts to isolate corresponding cDNAs using a modified hybrid selection technique. cDNAs using a modified hybrid selection technique. cDNAs from the region were identified and used to search for sequence similarity in human or other species. One cDNA clone was found to have 89% sequence similarity to the bovine B22 subunit of NADH-ubiquinone oxidoreductase, a mitochondrial protein in the respiratory electron transport chain. Given the history of other mitochondrial mutations being involved in hearing loss syndromes, this gene should be considered a strong candidate for involvement in BOR.},
doi = {10.1006/geno.1996.0316},
journal = {Genomics},
number = 1,
volume = 35,
place = {United States},
year = 1996,
month = 7
}
  • The soluble glutathione transferases (GSTs) are a family of dimeric isoenymes catalyzing the conjugation of glutathione to hydrophobic electropiles. Their subunits can be grouped into four families, alpha, mu, pi, and theta, on the basis of their primary structures. In man, the pi class is represented by a single gene, GSTP1-1 (GST[pi]) localized to human chromosome 11, band q13. The oncogenes INT2, HSTF1, and PRAD1 are also localized at 11q13, and together with the GSTP1 locus and other gene loci mapped to 11q13, i.e., BCL1 and EMS1, they form a unit of DNA approximately 2000-2500 kb, known as the 11q13more » amplicon, which is often amplified in a range of solid tumors. Any gene locus at 11q13 is of interest because it may influence tumorigenesis. 14 refs., 1 fig.« less
  • The NADH dehydrogenase complex isolated from Paracoccus denitrificans is composed of approximately 10 unlike polypeptides and contains noncovalently bound FMN, non-heme iron, and acid-labile sulfide. The NADH-binding subunit of this enzyme complex was identified by direct photoaffinity labeling with ({sup 32}P)NADH. primers were synthesized on the basis of the N-terminal amino acid sequency of this polypeptide, and these primers were used to synthesize an oligonucleotide probe by the polymerase chain reaction. This probe was utilized to isolate the gene encoding the NADH-binding subunit from a genomic library of P. denitrificans. The nucleotide sequence of the gene and the deduced aminomore » acid sequence of the entire NADH-binding subunit were determined. The NADH-binding subunit has 431 amino acid residues and a calculated molecular weight of 47 191. The encoded protein contains a putative NAD(H)-binding and an iron-sulfur cluster-binding consensus sequence. The deduced amino acid sequence of the Paracoccus NADH-binding subunit shows remarkable similarity to the {alpha} subunit of the NAD-linked hydrogenase of Alcaligenes eutrophus H16. When partial DNA sequencing of the regions surrounding the gene encoding the NADH-binding subunit was carried out, sequences homologous to the 24-, 49-, and 75-kDa polypeptides of bovine complex 1 were detected, suggesting that the structural genes of the Paracoccus NADH dehydrogenase complex constitute a gene cluster.« less
  • The NADH dehydrogenase complex isolated from Paracoccus denitrificans is composed of approximately 10 unlike polypeptides and contains noncovalently bound FMN, non-heme iron, and acid-labile sulfide. When the Paracoccus NADH dehydrogenase complex was irradiated by UV light in the presence of (adenylate-{sup 32}P)NAD, radioactivity was incorporated exclusively into one of three polypeptides of M{sub r} {approximately}50,000. Similar results were obtained when (adenylate-{sup 32}P)NADH was used. The labeling of the M{sub r} 50,000 polypeptide was diminished when UV irradiation of the enzyme with (adenylate-{sup 32}P)NAD was performed in the presence of NADH, but not in the presence of NADP(H). The labeled polypeptidemore » was isolated by preparative sodium dodecyl sulfate gel electrophoresis and was shown to cross-react with antiserum to the NADH-binding subunit of bovine NADH-ubiquinone oxidoreductase. Its amino acid composition was also very similar to that of the bovine NADH-binding subunit. These chemical and immunological results indicate that the M{sub r} 50,000 polypeptide is an NADH-binding subunit of the Paracoccus NADH dehydrogenase complex.« less
  • Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder associated with external-, middle-, and inner-ear malformations, branchial cleft sinuses, cervical fistulas, mixed hearing loss, and renal anomalies. The gene for BOR was mapped to the long arm of chromosome 8q. Several polymorphic dinucleotide repeat markers were investigated for linkage in two large BOR families, and the region of localization was refined. Two-point linkage analysis yielded the maximum lod scores of 7.44 at {theta} = .03 and 6.71 at {theta} = .04, with markers D8S279 and D8S260, respectively. A multipoint analysis was carried out to position the BOR gene with a definedmore » region using markers D8S165, D8S285, PENK, D8S166, D8S260, D8S279, D8S164, D8S286, D8S84, D8S275, D8S167, D8S273, and D8S271. Haplotype analysis of recombination events at these polymorphic loci was also performed in multigeneration BOR kindreds. The linkage analysis and analysis of recombination events identified markers that clearly flank the BOR locus. The order was determined to be D8S260-BOR-D8S279 at odds > 10{sup 3}:1 over the other possible orders. This flanking markers provide a resource for high-resolution mapping toward cloning and characterizing the BOR gene.« less
  • Branchio-oto-renal (BOR) syndrome is an autosomal dominant condition of branchial arch anomalies, deafness and renal dysplasia. Clinical manifestations tend to have considerable intrafamilial and interfamilial variability. Previous linkage studies had localized the gene responsible for BOR syndrome to a broad region of chromosome 8q. Using 10 microsatellite markers, we have further refined the localization of this disorder by establishing tight linkage to two markers, D8S279 and D8S530 (Z{sub max} = 3.91 and Z{sub max} = 2.83 respectively at {circle_minus} = 0.00). These markers are within 1 cM of one another. Multipoint analysis, involving 7 loci, placed the gene between thesemore » markers, with a lod-1 confidence interval 0.7 cM proximal to D8S530 and 0.6 cM distal to D8S279. 25 refs., 2 figs., 1 tab.« less