A GENE CAUSING HERMANSKY-PUDLAK SYNDROME IN A PUERTO-RICAN POPULATIONMAPS TO CHROMOSOME 10Q2

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder tha t affects pigment production and platelet function and causes the depo sition of a ceroid-like material in various tissues. Variability in th e phenotype and the presence of several potential mouse models suggest that HPS may be a heterogeneous disorder. In order to identify a gene responsible for HPS, we collected blood samples from a relatively hom ogeneous population in Puerto Rico where the HPS carrier frequency is estimated to be 1 in 21. Analysis of pooled DNA samples allowed us to rapidly screen the genome for candidate loci, and significant evidence for linkage was detected for a marker on chromosome 10q. This region of the human genome is conserved syntenically with the region on mouse chromosome 19 where two possible mouse models for HPS, pale ear and r uby eye, are located. This linkage result was verified with additional markers, and a maximum LOD score of 5.07 at theta = .001 was calculat ed for marker D10S198. Haplotype analysis places the HPS gene in a reg ion of similar to 14 cM that contains the markers D10S198 and D10S1239 .