Detection of the carrier state for an X-linked disorder, the Lesch-Nyhan syndrome, by the use of lymphocyte cloning.
Using a limiting dilution technique, we found that the frequency of thioguanine resistant (TGR) lymphocyte clones was less than 5.0 X 10(-5) in 14 normal individuals, between 9.0 X 10(-3) and 8.9 X 10(-2) in seven heterozygotes for Lesch-Nyhan syndrome, and 0.88 and 0.87 in two hemizygotes. TGR clones from heterozygotes were expanded and had the hemizygote phenotype as evidenced by low hypoxanthine incorporation and severely deficient hypoxanthine-guanine-phosphoribosyl-transferase activity. Enumeration of TGR lymphocyte clones provides a simple technique for detection of heterozygosity for Lesch-Nyhan syndrome. A similar approach using lymphocyte cloning may be suitable for detection of the carrier state for other X-linked disorders.
D002999:Clone Cells; D004351:Drug Resistance; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D007926:Lesch-Nyhan Syndrome / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D013866:Thioguanine / Q000494:pharmacology
D013866:Thioguanine