How could one begin to genetically dissect a trait like RP that shows nonallelic heterogeneity? pproach 1: Linkage analysis on large families with many affected individuals Different families with RP may show linkage to different loci, combining LOD scores from different families might obscure rather than clarify the situation However, this trap can be avoided if one can identify a family with sufficient numbers of affected individuals (and informative meioses to provide, by itself. a lod score of 3 Approach 2: Direct search for mutations in candidate genes In some diseases, one can make good guesses as to the biochemical structures or pathways that are likely sites of causative mutations. In such cases, a direct search for mutations at the dNa sequence level in candidate genes"--can be an effective strategy--even in the absence of any prior genetic linkage analysisHow could one begin to genetically dissect a trait like RP that shows nonallelic heterogeneity? Approach 1: Linkage analysis on large families with many affected individuals. combining LOD scores from different families might obscure rather than clarify the situation. However, this trap can be avoided if one can identify a family with sufficient numbers of affected individuals (and informative meioses) to provide, by itself, a LOD score of 3. Approach 2: Direct search for mutations in candidate genes. In some diseases, one can make good guesses as to the biochemical structures or pathways that are likely sites of causative mutations. In such cases, a direct search for mutations at the DNA sequence level in "candidate genes" -- can be an effective strategy -- even in the absence of any prior genetic linkage analysis. Different families with RP may show linkage to different loci