Molecular analysis of functional and nonfunctional genes for human ferrochelatase: Isolation and characterization of a FECH pseudogene and its sublocation on chromosome 3

Journal Article · Fri Apr 01 04:00:00 EST 1994 · Genomics; (United States)

DOI:https://doi.org/10.1006/geno.1994.1204· OSTI ID:6903769

Whitcombe, D M; Albertson, D G ^[1]; Cox, T M ^[2]

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1. Univ. of Cambridge (United Kingdom)
2. New Addenbrooke's Site, Cambridge (United Kingdom)

A pseudogene related to the functional gene (FECH) for the heme biosynthetic enzyme ferrochelatase (ferroheme-protolyase; EC 4.99.1.1.) was isolated from a human genomic library using a ferrochelatase cDNA hybridization probe. The pseudogene shows >80% overall nucleotide sequence identity to the functional gene (including the 3[prime] untranslated region and polyadenylation signals) but contains no intronic sequences in the region corresponding to the open reading frame of expressed ferrochelatase. Furthermore, the pseudogene sequence contains small deletions and insertions creating frameshifts and numerous termination codons, indicating that it does not encode a functional polypeptide. Northern blot analysis using pseudogene-specific probes failed to demonstrate transcripts in samples of human erythroid cell RNA in which ferrochelatase mRNA was readily detected. Southern blot experiments using restriction endonuclease-digested human genomic DNA probed either with ferrochelatase-specific cDNA fragments or pseudogene-specific genomic sequences confirmed the presence of distinct loci for the expressed and nonfunctional genes, respectively. Localization of the human ferrochelatase pseudogene to 3p22-p23 was determined by fluorescent metaphase chromosomal hybridization in situ using three genomic clones in [lambda]EMBL3 spanning a contiguous region of [approximately] 30 kb. This newly identified locus, distinct from the expressed FECH gene, on 18q22, is characteristic of a processed human pseudogene. The existence of the ferrochelatase pseudogene has practical implications for the molecular analysis of mutations responsible for erythropoietic protoporphyria in man. 24 refs., 3 figs.

• OSTI ID: 6903769
• Journal Information: Genomics; (United States), Journal Name: Genomics; (United States) Vol. 20:3; ISSN GNMCEP; ISSN 0888-7543
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
BIOSYNTHESIS
CARBOXYLIC ACIDS
CHROMOSOMES
DNA SEQUENCING
ENZYMES
GENE REGULATION
GENES
GENETIC MAPPING
HEME
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HUMAN CHROMOSOME 3
HUMAN CHROMOSOMES
LYASES
MAPPING
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIGMENTS
PORPHYRINS
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS
SYNTHESIS