Comparative mapping and structural analysis of a FOX gene cluster on bovine chromosome 18

Abstract

FOX genes encode a family of transcription factors which play important roles during early development and in regulation of metabolic homeostasis in mammals. Some members of the gene family, including FOXC2, FOXF1, and FOXL1 genes comprise a gene cluster on particular regions of human and mouse chromosomes. In this paper, we report chromosomal localization and structure of bovine FOXC2, FOXF1 and FOXL1 gene cluster and comparative analysis of the gene cluster in cattle, human, and mouse, which were performed by a combination of in silico database searching and in vitro sequencing and mapping experiments. BLAST search of cattle database with cDNA sequences of human and mouse FOXC2, FOXF1 and FOXL1 genes identified several ESTs which represent cattle cDNAs of these genes. Radiation hybrid mapping of these cattle cDNAs revealed that the bovine FOXC2, FOXL1, and FOXF1 genes are localized on the proximal region of bovine chromosome 18 and form a gene cluster. A comparative map of the region including the FOX gene cluster between cattle and human indicated that the localization of these genes on cattle chromosome is in concordant with those in the corresponding human chromosome. Then, we identified a contig of BAC draft sequences containing genomic sequences of these genes by MEGABLAST search of a cattle genome database using the cattle cDNA sequences. Complete genomic sequences of these genes were determined by cloning and sequencing of a part of genomic region in which the nucleotide sequences could not be obtained from the published BAC draft sequences. A comparison of the nucleotide sequences of the cattle, human, and mouse FOX gene clusters showed highly conserved structure of the cluster in mammalian species and identified some potential regulatory regions which are conserved in mammalian species.