A NOVEL MICROSATELLITE POLYMORPHISM IN THE HUMAN OB GENE - A HIGHLY POLYMORPHIC MARKER FOR LINKAGE ANALYSIS

The mouse ob gene and its human homologue OB have recently been cloned . The mutations in the ob gene are known to be associated with extreme obesity The relationship between the human OB gene and disease, howev er, is largely unknown due to the lack of suitable markers within or a djacent to the OB gene. To obtain Informative markers, we searched for simple tandem repeat polymorphisms in the genomic sequence of the hum an OB gene and identified a novel tetranucleotide repeal in the 3' nan king region. Fifteen alleles were detected in this marker with a heter ozygosity of 0.85 and polymorphism information content of 0.83, indica ting a highly informative nature of this marker. Two-point linkage map ping in two Centre Etude Polymorphisme Humaine (CEPH) reference famili es suggested that this marker is Located in the interval between D7S51 4 and D7S530, the same interval where the OB gene is located (recombin ation fractions with D7S514 and D7S530 were 0.026 and 0.034, respectiv ely). Although allele frequency distributions of this marker did not d iffer between 84 control subjects and 69 NIDDM patients, there was a t endency to higher body weight in control subjects with class I/class I genotype than in those without this genotype (68.8 +/- 11.1 vs 60.8 /- 10.3 kg, p = 0.05). The highly polymorphic nature of this marker an d its location in the OB gene makes this marker useful Tor linkage stu dies of the OB gene with a number of phenotypes, such as obesity, non- insulin-dependent diabetes mellitus, hypertension and the insulin resi stance syndrome.