Genetic variability and evolution of two pharmacologically important classes of genes.

We have studied the human genetic variability of single nucleotide polymorphisms (SNPs) and haplotypes in two pharmaceutically important classes of genes that might be expected to experience different evolutionary pressures: antigen presentation and processing (APP) and nuclear hormone receptor (NHR) genes. We compared the variation pattern in these two classes of genes with 5119 reference (REF) genes. We assessed this variability by sequencing and discovering SNPs in 5'-upstream, 5'-untranslated region (5'UTR), exon, intron, 3'UTR and 3'-downstream regions of all these genes in 79 unrelated humans from diverse ethnic backgrounds, one chimpanzee (Pan troglodytes) and a gorilla (Gorilla gorilla).

Gene and protein domain-specific patterns of genetic variability within the G-protein coupled receptor superfamily.

Introduction: Guanine nucleotide binding proteins (G-proteins) represent the targets for >50% of all therapeutics. There is substantial interindividual variation in response to agonists and antagonists directed to these receptors, which may, in part, be due to genetic polymorphisms. As a class, the sequence variability of G-protein-coupled receptor (GPCR) genes has not been characterized.

The Chediak-Higashi protein interacts with SNARE complex and signal transduction proteins.

Background: Chediak-Higashi syndrome (CHS) is an inherited immunodeficiency disease characterized by giant lysosomes and impaired leukocyte degranulation. CHS results from mutations in the lysosomal trafficking regulator (LYST) gene, which encodes a 425-kD cytoplasmic protein of unknown function. The goal of this study was to identify proteins that interact with LYST as a first step in understanding how LYST modulates lysosomal exocytosis.