The gene map of Homo sapiens: status and prospectus.

The first gene to be mapped to a specific chromosome in man indeed, in any mammal was that for color blindness, deduced to be on the X chromosome by E.B. Wilson at Columbia University in 1911. A few dozen other X-linked traits (e.g., hemophilia and Duchenne muscular dystrophy) were identified by characteristic pedigree pattern during the next 57 years before the first assignment of a gene to a specific human autosome: Duffy blood group to chromosome 1 by Donahue and colleagues (1968) at Johns Hopkins University. They made the assignment by finding evidence of linkage between the Duffy locus and a heteromorphism of chromosome 1 that was segregating in a Mendelian manner in Donahue’s family. Soon thereafter, haptoglobin was assigned to chromosome 16 by linkage studies in families with inherited, balanced translocations involving 16 (Robson et al. 1969) and in families with a heritable “fragile site” on 16q (Magenis et al. 1970). About the same time, Weiss and Green (1967) showed the feasibility of assigning specific genes to specific chromosomes (or regions of chromosomes) by interspecies somatic cell hybridization (SCH) (e.g., fusion of cells from mouse and man), a method of genetic study called “parasexual” by Pontecorvo and “an alternative to sex” by Haldane. Between 1951, when the first successful autosomal assignment of a gene was achieved by the linkage method, and 1968, when the fruitful, alternative mapping method of SCH was introduced, nine autosomal linkages in man (seven pairs, one triplet, and one foursome) had been established by family studies, but the specific autosome carrying each of the linkage groups was not known. For the linkage studies in man, special methods of analysis of pedigree data were necessary because it is not possible to design matings as can be done in experimental organisms. The sib-pair method of Penrose, for example, was used by Mohr in 1951 to establish the first autosomal linkage, that between Lutheran blood group and secretor trait. The method of “lods” (log odds) was elaborated by C.A.B. Smith and