Identifying genes for alcohol and drug sensitivity: recent progress and future directions.
New methods for identifying chromosomal regions containing genes that affect murine responses to alcohol and drugs have been used to identify many provisional quantitative trait loci (QTLs) since 1991. By 1998, 24 QTLs had been definitively mapped (P<5x10(-5)) to specific murine chromosomes, which indicates the presence of a relevant gene or genes at each location. The syntenic (homologous) region of the human genome for these genes is often known. For many mapped QTLs, candidate genes with relevant neurobiological function lie within the mapped region. Data that implicate candidate genes for specific responses include studies of knockout animals. Current strategies for gene identification include the use of congenic strains containing QTL regions introduced from another strain. There is increasing emphasis on gene-gene and gene-environment interactions in such studies.
Crabbe
J C
JC
Portland Alcohol Research Center, the Veterans Affairs Medical Center and the Dept of Behavioral Neuroscience, Oregon Health Sciences University, Portland, OR 97201, USA.
Phillips
T J
TJ
Buck
K J
KJ
Cunningham
C L
CL
Belknap
J K
JK
D000428:Alcohol Drinking / Q000235:genetics; D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002874:Chromosome Mapping; D003042:Cocaine / Q000633:toxicity; D003433:Crosses, Genetic; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005544:Forecasting; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009020:Morphine / Q000633:toxicity; D010424:Pentobarbital / Q000633:toxicity; D019655:Quantitative Trait, Heritable; D013375:Substance Withdrawal Syndrome / Q000235:genetics; D019966:Substance-Related Disorders / Q000235:genetics*
D000431:Ethanol; D009020:Morphine; D010424:Pentobarbital; D003042:Cocaine