in each genomic location between affected relatives compared to the expected allele sharing for each type of pair of relatives. This makes a sacrifice in power, but avoids assumptions about inheritance, bypassing a significant problem of parametric linkage. At the same time, technologies were developed allowing genotyping of short tandem repeat (STR) markers without polyacrylamide gels or radioactivity and with extensive marker multiplexing. It became possible to survey the genome at a cost and time investment that was realistic. Whole genome linkage studies were soon being published monthly or weekly. The results, however, did not deliver on the expectations. Linkage signals were most often weak, not providing the strong evidence for disease loci everyone hoped for. In 1995 Lander and Kruglyak (14) formalized the criteria for declaring genome-wide significant linkage. Very few studies met these criteria and the few loci that did almost invariably did not replicate in other samples. Complex disease genetics and psychiatric genetics were going through a confidence crisis.
