Identification and characterization of a novel gene disrupted by a pericentric inversion inv(4)(p13.1q21.1) in a family with cleft lip

Soraya Beiraghi, Ming Zhou, Catherine B. Talmadge, Nils Went-Sumegi, Jack R. Davis, Dali Huang, Howard Saal, Thomas A. Seemayer, Janos Sumegi

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Cleft lip with or without cleft palate is a common birth defect affecting 1 in every 700 live births. Several genetic loci are believed to be involved in the pathogenesis of syndromic and non-syndromic clefting. We identified a pericentric inversion of chromosome 4, inv(4)(p13q21) that segregates with cleft lip in a two-generation family. By using a combination of fluorescence in situ hybridization, yeast artificial chromosome, bacterial artificial chromosome contig mapping, and database searching we mapped and sequenced the inversion breakpoint region. The pericentric inversion disrupts a gene (ACOD4) on chromosome 4q21 that codes for a novel acyl-CoA desaturase enzyme. The 3.0 kb human ACOD4 cDNA spans approximately 170 kb and is composed of five exons of ACOD4. The inversion breakpoint is located in the second exon. The 3.0 kb mRNA is expressed at high level in fetal brain; a lower expression level was found in fetal kidney. No expression of ACOD4 was detected in fetal lung or liver or in adult tissues. The five exons code for a protein of 330 amino acids, with a predicted molecular weight of 37.5 kDa. The protein is highly similar to acyl-CoA desaturases from Drosophila melanogaster to Homo sapiens. The catalytically essential histidine clusters and the potential transmembrane domains are well conserved.

Original languageEnglish (US)
Pages (from-to)11-21
Number of pages11
JournalGene
Volume309
Issue number1
DOIs
StatePublished - Apr 24 2003

Bibliographical note

Funding Information:
This investigation was supported by NIH grant DE11597-02. We thank Joseph S. Edwards for the artwork.

Keywords

  • Acyl-CoA-desaturase
  • Chromosomal rearrangement

Fingerprint Dive into the research topics of 'Identification and characterization of a novel gene disrupted by a pericentric inversion inv(4)(p13.1q21.1) in a family with cleft lip'. Together they form a unique fingerprint.

Cite this