One-stage versus two-stage strategies for genome scans.

One way to determine the genetic etiology of a complex disease is to find the chromosomal regions that tend to be shared among affected relatives and yet tend to differ between affected and unaffected relatives. This can be done by using equally spaced markers to perform a global linkage search of the whole genome. With the rapid development of molecular technology to readily type individuals, it is becoming relatively easy to carry out such genome searches for disease genes. The simplest approach is to type every individual in the sample at every marker locus. However, such an approach wastes a great deal of effort in genotyping large areas of the genome that are eventually found not to show any evidence for linkage. Efficient design of genome scans for linkage analysis is therefore an important issue. We first describe strategies in which a single sample is typed for markers in one or two stages, with neither the use of a second sample nor any attempt at replication of a linkage result. Then in the discussion we briefly mention other multistage strategies, including one that involves a degree of replication.