Identification and characterization of a novel gene disrupted by a pericentric inversion inv(4)(p13.1q21.1) in a family with cleft lip.
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.
Beiraghi
Soraya
S
Division of Pediatric Dentistry, University of Minnesota, 6-150 Moos Tower, 515 Delaware Street SE, Minneapolis, MN 55455, USA. beira.001@tc.umn.edu
Zhou
Ming
M
Talmadge
Catherine B
CB
Went-Sumegi
Nils
N
Davis
Jack R
JR
Huang
Dali
D
Saal
Howard
H
Seemayer
Thomas A
TA
Sumegi
Janos
J
D000595:Amino Acid Sequence; D002460:Cell Line; D019457:Chromosome Breakage / Q000235:genetics; D007446:Chromosome Inversion; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002971:Cleft Lip / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D020451:Contig Mapping; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D004247:DNA; D044943:Fatty Acid Desaturases