We describe a new basis for the construction of a genetic linkage map of the human genome. The basic principle of the mapping scheme is to develop, by recombinant DNA techniques, random single-copy DNA probes capable of detecting DNA sequence polymorphisms, when hybridized to restriction digests of an individual's DNA. Each of these probes will define a locus. Loci can be expanded or contracted to include more or less polymorphism by further application of recombinant DNA technology. Suitably polymorphic loci can be tested for linkage relationships in human pedigrees by established methods; and loci can be arranged into linkage groups to form a true genetic map of "DNA marker loci." Pedigrees in which inherited traits are known to be segregating can then be analyzed, making possible the mapping of the gene(s) responsible for the trait with respect to the DNA marker loci, without requiring direct access to a specified gene's DNA. For inherited diseases mapped in this way, linked DNA marker loci can be used predictively for genetic counseling.

Construction of a genetic linkage map in man using restriction fragment length polymorphisms.

Summary Human embryonic kidney cells have been transformed by exposing cells to sheared fragments of adenovirus type 5 DNA. The transformed cells (designated 293 cells) exhibited many of the characteristics of transformation including the elaboration of a virus-specific tumour antigen. Analysis of the polypeptides synthesized in the 293 cells by labelling with 35S-methionine and SDS PAGE showed a variable pattern of synthesis, different in a number of respects from that seen in other human cells. On labelling the surface of cells by lactoperoxidase catalysed radio-iodination, the absence of a labelled polypeptide analogous to the 250 K (LETS) glycoprotein was noted. Hybridization of labelled cellular RNA with restriction fragments of adenovirus type 5 DNA indicated transcription of a portion of the adenovirus genome at the conventional left hand end.

Characteristics of a Human Cell Line Transformed by DNA from Human Adenovirus Type 5

https://www.cell.com/cell/pdf/0092-8674(81)90282-8.pdf

SV40-transformed simian cells support the replication of early SV40 mutants.

https://www.cell.com/cell/pdf/0092-8674(82)90356-7.pdf

Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells

In the mid-1980s, the development of abundant molecular markers, appropriate statistical pro- cedures, and user-friendly computer software that implemented these statistical procedures permitted the detection of molecular markers associated with quantitative trait loci (QTL) for complex traits. Marker-assisted selection was then proposed as a means of exploiting mark- ers linked to QTL to develop improved cultivars. But while thousands of marker-trait associations have been reported for many traits in different plant species, far fewer examples of success- fully exploiting mapped QTL have been reported in the literature. Key lessons learned from apply- ing markers in plant breeding include the follow- ing: (i) the purpose of detecting QTL should be clearly defi ned before embarking on QTL map- ping; (ii) procedures for marker-based selection depend on the number of QTL; (iii) estimates of QTL effects for complex traits are often incon- sistent; and (iv) gain per unit cost and time rather than gain per cycle should be considered. Future applications for complex traits will likely focus on predictive methodologies for marker-based selection before phenotyping and for marker- based selection without QTL mapping. These applications will take advantage of cheaper costs of genotyping than of phenotyping.

/pdf/molecular-markers-and-selection-for-complex-traits-in-plants-2z2qfex7a3.pdf

Molecular Markers and Selection for Complex Traits in Plants: Learning from the Last 20 Years

Host-range mutants of adenovirus type 5 defective for growth in HeLa cells.

Physical mapping of temperature-sensitive mutations of adenoviruses.

Viral nucleic acid sequences in transformed cells: IV. A study of the sequences of adenovirus 5 DNA and RNA in four lines of Adenovirus 5-transformed rodent cells using specific fragments of the viral genome

In accord with the nomenclature proposed for mutants of simian virus 40 the same rules, with minor modifications, are recommended for naming mutants of adenoviruses. It is further suggested that these rules, which pertain to a system of classification based primarily upon complementation analysis, also be applied to mutants of other DNA-containing animal viruses.

Jim Williams

Papers

Host-range mutants of adenovirus type 5 defective for growth in HeLa cells.

Physical mapping of temperature-sensitive mutations of adenoviruses.

Viral nucleic acid sequences in transformed cells: IV. A study of the sequences of adenovirus 5 DNA and RNA in four lines of Adenovirus 5-transformed rodent cells using specific fragments of the viral genome

Proposed Nomenclature for Mutants of Adenoviruses