International Mammalian Genome Society

I16 The Search for Behavioral SNPs

Kira K. Lueders and Dean Hamer. Lab. of Biochemistry, National Cancer Institute, NIH, Bethesda, MD 20892 USA

Although many aspects of human behavior and personality are genetically influenced, finding genes for such complex traits is difficult because many different loci are involved and environment and life experiences play an equally important role. Our laboratory has used a candidate gene approach to seek genes for traits such as novelty seeking (Nature Genetics 12:81, 1996), anxiety (Science 274:1527, 1996), and cigarette smoking (Health Psych. 18:7, 1999), but this approach is circumscribed by our limited understanding of the underlying neurobiology. SNPs offer a potential solution, since they are major contributors to genetic variation, occur frequently, and are less subject to mutation than other types of polymorphisms. As a first step, we have isolated a genomic clone for the beta2 nicotinic acetylcholine receptor (Mammalian Genome, in press) and constructed an SNP map for the gene. Beta2-subunits are of particular interest because they are the most widely expressed in the nervous system and participate in over 90% of the high-affinity nicotine binding sites in the brain. In addition to SNP identification by sequencing DNAs from 10 CEPH samples, we have defined an additional 2.7 kb of sequence not previously recognized to be part of this gene, and have used this information to identify entries in the EST database for SNP discovery in silico. Use of this technology to analyze the role of the beta2 nicotinic receptor in cigarette smoking behavior will be described.