Linkage analysis in the discovery of disease genes.(a) These pedigrees for two families affected by early-onset Alzheimer disease are based on the data available at the time of the study. Filled symbols represent affected individuals; slashes indicate deaths. The number above each symbol is the person’s age at onset of symptoms (for affected individuals), or age at the time of the study (for living unaffected individuals), or age at time of death (for deceased unaffected individuals and others marked by “D”). Black dots indicate that an autopsy was done to verify the presence of Alzheimer disease. To protect family privacy, gender is not indicated. (b) Chromosome 14 has marker positions shown at the right, with the genetic distance between them in centimorgans. TCRD (T-cell receptor delta) and PI (AACT, α1-antichymotrypsin) are genes with variations in the human population that were used as markers, along with SNPs, in chromosome mapping. (c) A region of interest containing 19 expressed genes was eventually defined near marker D14S43. The gene labeled S182 (red) encodes presenilin-1. (Mb indicates 10⁶ bases.)