Molecular structure of the Menkes disease gene (ATP7A)

Journal Article · Thu Aug 10 04:00:00 EDT 1995 · Genomics

DOI:https://doi.org/10.1006/geno.1995.1175· OSTI ID:390668

Dierick, H A; Glover, T W ^[1]; Ambrosini, L ^[2]

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1. Univ. of Michigan, Ann Arbor, MI (United States)
2. Murdoch Institute, Victoria (Australia); and others

We report a detailed molecular analysis of the genomic structure of the Menkes disease gene (MNK; ATP7A). There are 23 exons in ATP7A covering a genomic region of approximately 140 kb. The size of the individual coding exons varies between 77 and 726 bp, and introns vary in size between 196 bp and approximately 60 kb. All of the splice sites obey the consensus GT-AG rule except the splice donor of intron 9, which is GC instead of GT. The exon following this rare splice donor variant is alternatively spliced. A PGAM pseudogene and two highly polymorphic CA repeats map to introns within the gene. The structure is very similar to that of the closely related Wilson disease gene (WND; ATP7B). From exon 5 (exon 3 in ATP7B) to the end, all of the splice sites occur at exactly the same nucleotide positions as in the WND gene, except for the boundary between exons 17 and 18 (exons 15 and 16 in ATP7B) and a single codon difference at the boundary between exons 4 and 5 of the MNK gene (exons 2 and 3 in ATP7B). In contrast to the WND gene, in which the first four of six metal binding domains are contained in 1 exon, metal binding domains 1 to 4 are divided over 3 exons. The striking similarity of the MNK and WND genes at the genomic level is consistent with their relatively recent divergence from a common ancestral gene. 39 refs., 4 figs., 1 tab.

• OSTI ID: 390668
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 3 Vol. 28; ISSN 0888-7543; ISSN GNMCEP
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL EVOLUTION
CODONS
COPPER
DNA SEQUENCING
DNA-CLONING
EXONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN X CHROMOSOME
INTRONS
METABOLIC DISEASES
METABOLISM
NUCLEOTIDES
POLYMERASE CHAIN REACTION
RECESSIVE MUTATIONS
SPLICING
STRUCTURE-ACTIVITY RELATIONSHIPS