A new location for the human adenine phosphoribosyltransferase gene (<i>APRT</i>) distal to the haptoglobin (<i>HP</i>) and fra(16)(q23) (<i>FRA16D</i>) loci

Abstract

The human adenine phosphoribosyltransferase gene (APRT) was mapped with respect to the haptoglobin gene (HP) and the fragile site at 16q23.2 (FRA16D). A subclone of APRT and a cDNA clone of HP were used for molecular hybridization to DNA from mouse-human hybrid cell lines containing specific chromosome 16 translocations. The APRT subclone was used for in situ hybridization to chromosomes expressing FRA16D. APRT was found to be distal to HP and FRA16D and was localized at 16q24, making the gene order cen-FRA16B-HP-FRA16D-APRT-qter.

Genetic linkage map of 46 DNA markers on human chromosome 16.

“…1 along with an ideogram of chromosome 16 indicating the subchromosomal localization of HBAJ to 16pl3.3 (24), HP to 16q22.1 (25), and both APRT and D16S7 to 16q24 (26,13). The subchromosomal location of 16 other loci on the map was determined by hybridization to the hybrid cell lines CH1-16 and GM6227.…”

Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis.

“…APRT deficiency is inherited in an autosomal recessive manner, consistent with the localization of the single-copy gene to 16q24 (8). Heterozygous carriers are usually unaffected, although one affected heterozygous male has been reported (9).…”

“…Adenine is produced endogenously as a by-product of the polyamine pathway and by the reaction of adenosine with S-adenosylhomocysteine hydrolase (2,3). In the absence of functional APRT, adenine is oxidized by xanthine dehydrogenase (XDH; EC 1.2.3.2), by an 8-hydroxy intermediate, to 2,8-dihydroxyadenine (DHA) (4). The sparingly soluble nature of DHA at the normal pH of human urine (5) results in the excretion of DHA crystals in the urine and, frequently, the deposition of DHA stones in the kidneys.…”

A fragile site in the human U2 small nuclear RNA gene cluster is revealed by adenovirus type 12 infection.

“…We predict, therefore, ti frequency within any of the U2 gene repeat, equal numbe and distally to the site of dai in situ data, however, does n 0.001). Second, the observati On the basis of our data, we suggest that the data regarding the mapping of the human metallothionein, haptoglobin, and adenine phosphoribosyltransferase genes relais of U2 genes in Adl2-infected (A) tive to the fragile sites at 16q (3,17,18) should be reevalus. DNA samples were digested with ated.…”