Germ-line chromosomal localization of genes in chromosome 11p linkage: parathyroid hormone, beta-globin, c-Ha-ras-1, and insulin.

The chromosomal localization of genes for parathyroid hormone (PTH), beta-globin cluster, c-Ha-ras-1, and insulin, all of which have previously been assigned to the short arm of chromosome 11, generated considerable interest because of their association with development of disease states. Furthermore, the availability of recombination data from family studies made the determination of their physical location on the chromosome necessary. Several investigators have attempted this; however, controversy has arisen concerning the location of beta-globin, insulin, and c-Ha-ras-1 genes. Thus, while the results of some investigators suggested that all three genes are situated in the 11p15 region, data of other investigators placed the beta-globin and insulin genes close to the centromere and c-Ha-ras-1 in a more proximal region than 11p15. The subchromosomal position of the PTH gene remains to be determined. We have performed in situ hybridization of meiotic pachytene bivalents with 3H-labeled cloned genomic probes of PTH, beta-globin, and insulin genes and find their germ-line positions to be the following: PTH at 11p11.21, beta-globin at 11p11.22, and insulin at 11p14.1. These data, when considered with our recent germ-line assignment of the c-Ha-ras-1 gene to 11p14.1, indicate the following relative order on 11p: cen-PTH-beta-globin-c-Ha-ras-insulin or cen-PTH-beta-globin-insulin-c-Ha-ras. The former order is consistent with genetic evidence from linkage analysis of DNA polymorphisms adjacent to these genes segregating in families.