HUMAN HOXB CLUSTER AND THE NERVE GROWTH-FACTOR RECEPTOR GENE - COMPARISON WITH AN ORTHOLOGOUS CHROMOSOMAL DOMAIN IN MOUSE

The structural organization and nucleotide sequence similarity of mamm alian Antennapedia-class homeobox genes support the view that the four homeobox clusters (HOXA, B, C, and D on human chromosomes 7, 17, 12, and 2, respectively) arose through a combination of gene duplication a nd divergence to form a cluster, followed by several cluster duplicati ons. The duplication events that gave rise to the four clusters appear to have involved chromosomal domains extending well beyond the border s of the clusters in either direction. This evidence arises from the o bservation that many genes closely linked to the homeobox clusters on different chromosomes show sequence similarity. Here, we present a con tinuation of physical mapping studies to determine the extent and orga nization of the duplicated regions surrounding the four homeobox clust ers in human. Southern blots prepared from pulsed-field gels of human DNA were probed with cloned segments of human HOXB genes and the nerve growth factor receptor (NGFR) gene on chromosome 17q21-q22. Restricti on enzyme analysis revealed the close physical linkage of these genes within 100 kb. Two yeast artificial chromosomes (YACs), 220 and 380 kb in size, were isolated using oligonucleotide primers specific for NGF R. Both YACs contained the entire HOXB cluster. Restriction mapping of the clones indicated that the distance separating these loci could no t be greater than 50 kb. This result confirms and extends previous inf ormation on the proximity of these genes as determined by genetic Link age analysis and closely parallels the orthologous loci in the mouse. (C) 1995 Academic Press, Inc.