Intrachromosomal gene mapping in man: Assignment of nucleoside phosphorylase to region 14cen?14q21 by interspecific hybridization of cells with a t(X;14) (p22;q21) translocation

Abstract

The structural gene for purine-nucleoside phosphorylase (NP) has been assigned to a subregion of chromosome 14 by somatic cell hybridization of male and female cells containing the balanced translocation t(X;14) (p22;q21). Peripheral lymphocytes were fused to a pseudodiploid HPRT-deficient established Chinese hamster cell line. 23 primary hybrid clones (10 derived from male and 13 from female cells) were isolated and maintained in HAT selective medium. Parallel subcultures from generations 16, 24, and 40 after clonal isolation were fully karyotyped and analyzed electrophorectically for expression of the human types of NP, HPRT, G6PD, and PGK. The human NP phenotype segregated discordantly with each human chromosome except chromosome 14 and the der(14),t(X;14) translocation chromosome. In all, 8 hybrids which had retained the der(X), t(X;14) translocation chromosome under HAT selective pressure and expressed human HPRT had lost the human NP phenotype. These results indicate localization of the NP gene in region 14pter leads to 14q21.

p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity

“…To identify this activating gene, binding activity was measured in several hamster-human hybrid cell lines (13,14,28,31) (Fig. 4A).…”

Genes coding for sensitivity to interferon (IfRec) and soluble superoxide dismutase (SOD-1) are linked in mouse and man and map to mouse chromosome 16.

“…Because mouse SOD-1 has been regionally mapped to the distal portion of mouse chromosome 16 (24), it will also be important to regionally map IfRec to determine if the distal segment of mouse chromosome 16 is homologous with that part of human chromosome 21 responsible for the DS phenotype.…”

“…Certain aspects of the DS phenotype, such as abnormal immune function, increased cellular radiation sensitivity, and leukemogenesis, may be caused by the altered dosage of IfRec and SOD-1 that occurs in individuals with trisomy 21. Because we have assigned both IfRec and SOD-1 to mouse chromosome 16, mice trisomic for this chromosome would provide a model system that could be used to determine if such a causal relationship exists between the dosage of IfRec and SOD-I and those aspects of DS mentioned above.…”

“…Hybrid cells were harvested for chromosome studies at the same time the cells were plated for the IfRec assay and extracts were prepared for enzyme electrophoresis. The chromosomes were identified by standard trypsin/Giemsa banding methods (21).…”

“…Despite the frequency of DS, little is known about the mechanisms by which trisomy for chromosome 21 interferes with normal development and function to produce the DS phenotype. Studies of partial translocations involving chromosome 21 have shown that trisomy for only band 21q22, which is located on the distal portion of the long arm of chromosome 21, will result in DS (5). Two human genes, IfRec (formerly AVG or AVP) and SOD-1 are known to map to this region of the chromosome (6,7).…”