THE HUMAN GAMMA-AMINOBUTYRIC-ACID RECEPTOR SUBUNIT BETA-3 AND ALPHA-5 GENE-CLUSTER IN CHROMOSOME 15Q11-Q13 IS RICH IN HIGHLY POLYMORPHIC (CA)(N) REPEATS

The gamma-aminobutyric acid (GABA(A)) receptor beta 3 (GABRB3) and alpha 5 (GABRA5) subunit genes have been localized to the Angelman and Prader-Willi syndrome region of chromosome 15q11-q13. GABRB3, which encompasses 250 kb, is located 100 kb proximal of GABRA5, with the two genes arranged in head-to-head transcriptional orientation. In screening 135 kb of cloned DNA within a 260-kb interval extending from within GABRB3 to the 5' end of GABRA5, 10 new (CA)(n) repeats have been identified. Five of these have been analyzed in detail and found to be highly polymorphic, with the polymorphism information content (PIC) ranging from 0.7 to 0.85 and with heterozygosities of 67 to 94%. In the clones from GABRB3/GABRA5 region, therefore, the frequency of (CA)(n) with PICs greater than or equal to 0.7 is 1 per 27 kb. Previous estimates of the density of (CA)(n) with PICs greater than or equal to 0.7 in the human genome have been approximately 10-fold lower. The GABRB3/GABRA5 region appears, therefore, to be enriched for highly informative (CA)(n). This set of closely spaced, short tandem repeat polymorphisms will be useful in the molecular analyses of Prader-Willi and Angelman syndromes and in high-resolution studies of genetic recombination within this region. (C) 1994 Academic Press, Inc.