Genomic characterization of the human peptidyl-prolyl-cis-trans-isomerase, mitochondrial precursor gene

Assessment of its role in familial dilated cardiomyopathy

Karla R. Bowles, Carmelann Zintz, Sherin E. Abraham, Lois Brandon, Neil E. Bowles, Jeffrey Towbin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Dilated cardiomyopathy (DCM) is a common cause of morbidity and mortality, with > 30% of cases being inherited. In one family with autosomal dominant familial dilated cardiomyopathy (FDCM), we localized the gene to the region of 10q21-10q23 and have performed candidate positional gene cloning. The peptidyl-prolyl-cis-trans-isomerase, mitochondrial precursor (PPIF: previously known as cyclophilin 3) is a protein that is part of the mitochondrial permeability transition pore, the activation of which is involved in the induction of necrotic and apoptotic cell death. Since it is encoded by a gene located within this FDCM critical region, PPIF was considered a potential candidate gene for FDCM. In order to screen patient genomes for evidence of disease-associated mutations, the genomic organization of this gene was determined. BAC libraries were screened by PCR, using primers designed from the published cDNA sequence, and positive clones were identified. This enabled the gene to be further localized to between the CEPH markers D10S1777 and D10S201. The DNA from a BAC clone was digested and subcloned into pUC18. Following identification of a subclone by whole-cell PCR, the gene was characterized by DNA sequencing; five introns were identified, and the sequences of the intron-exon boundaries were characterized. Additionally, 450 bp of DNA sequence upstream of the published cDNA were obtained and a potential transcription initiation site and promoter sequence were identified. DNA analysis of the entire PPIF coding region (including the intron-exon boundaries) of two affected and one unaffected family member revealed no mutations, therefore excluding this gene as the cause of FDCM in this family.

Original languageEnglish (US)
Pages (from-to)582-586
Number of pages5
JournalHuman genetics
Volume105
Issue number6
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

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Peptidylprolyl Isomerase
Mitochondrial Genes
Genes
Introns
Exons
Complementary DNA
Clone Cells
Cyclophilins
Polymerase Chain Reaction
Mutation
Familial dilated cardiomyopathy
Transcription Initiation Site
DNA
Dilated Cardiomyopathy
DNA Sequence Analysis
Libraries
Organism Cloning
Cell Death
Genome
Morbidity

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Genomic characterization of the human peptidyl-prolyl-cis-trans-isomerase, mitochondrial precursor gene : Assessment of its role in familial dilated cardiomyopathy. / Bowles, Karla R.; Zintz, Carmelann; Abraham, Sherin E.; Brandon, Lois; Bowles, Neil E.; Towbin, Jeffrey.

In: Human genetics, Vol. 105, No. 6, 01.01.1999, p. 582-586.

Research output: Contribution to journalArticle

Bowles, Karla R. ; Zintz, Carmelann ; Abraham, Sherin E. ; Brandon, Lois ; Bowles, Neil E. ; Towbin, Jeffrey. / Genomic characterization of the human peptidyl-prolyl-cis-trans-isomerase, mitochondrial precursor gene : Assessment of its role in familial dilated cardiomyopathy. In: Human genetics. 1999 ; Vol. 105, No. 6. pp. 582-586.
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