INCREASING THE EFFICIENCY OF GENOMIC SEARCHES FOR LINKAGE IN COMPLEX DISORDERS BY DNA POOLING OF AFFECTED SIB-PAIRS

Detection of linkage using a systematic genome scan in nuclear familie s including an affected sibling pair is an important initial step on t he path to cloning susceptibility genes for complex genetic disorders such as bipolar disorder and schizophrenia, We describe a novel method in which the pooled genotype of each affected sib-pair is determined and used in the screening stage of a two-stage genome scan, This metho d, which involves a single PCR reaction per sib-pair in the screening stage can reduce the required number of genotypings to less than 20% o f those required in a conventional single stage procedure whilst maint aining a similar power and probability of type I error.