Identification and characterization of KAT, a novel gene preferentially expressed in several human cancer cell lines.

We describe the molecular characterization of a novel human gene on chromosome 1q23.3, termed KAT, which is highly conserved among mammals. The KAT gene spans a genomic region of approximately 1.

Comparative sequencing of the human CB1 cannabinoid receptor gene coding exon: no structural mutations in individuals exhibiting extreme responses to cannabis.

Rare but striking individual differences in responsiveness to cannabinoids have been observed that might involve mutations in the gene encoding the brain-expressed cannabinoid receptor. In a preliminary study, the human CB1 cannabinoid receptor coding region was comparatively sequenced in different groups of individuals: one group showed acute psychotic symptoms after cannabis intake, while another group did not develop any psychopathology after long-term heavy cannabis abuse. No evidence for structural mutations was obtained, which might provide some insight into the molecular basis of individually different responsiveness to cannabinoids.

Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence.

To analyze candidate genes and establish complex genotype-phenotype relationships against a background of high natural genome sequence variability, we have developed approaches to (i) compare candidate gene sequence information in multiple individuals; (ii) predict haplotypes from numerous variants; and (iii) classify haplotypes and identify specific sequence variants, or combinations of variants (pattern), associated with the phenotype. Using the human mu opioid receptor gene (OPRM1) as a model system, we have combined these approaches to test a potential role of OPRM1 in substance (heroin/cocaine) dependence. All known functionally relevant regions of this prime candidate gene were analyzed by multiplex sequence comparison in 250 cases and controls; 43 variants were identified and 52 different haplotypes predicted in the subgroup of 172 African-Americans.