Cloning the genes for A and B blood types.

Cloning the genes for A and B blood types

Amid the fast-breaking findings in molecular biology, the identification of a couple more human genes may seem almost commonplace. But this time researchers have gone against type, cloning the genes that determine two major blood groups, A and B. Moreover, by inserting the cloned genes into type O blood cells -- which have no major blood-type markers, or antigens, of their own -- the scientists then induced these cells to produce the A and B antigens on their surfaces.

The new findings may eventually offer a method for altering the blood type of individuals, and may someday help blood bank technicians direct stored precursor blood cells to differentiate into a specific blood cell type. More immediately, the work may provide a tool for examining in unprecedented detail the parental contributions to each person's blood type, enabling forensic experts, for example, to more closely tie a suspect to the scene of a crime. In addition, says Sen-itiroh Hakomori of the the University of Washington in Seattle and the affiliated Biomembrane Institute, the findings suggest a new technique for combating certain cancers.

Hakomori and his colleagues analyzed the genes associated with the A and B antigens in blood cell lines belonging to the three major blood groups, A, B and O. The team reports in the May 17 NATURE that A and B genes differ by only four nucleotides -- the building blocks of DNA and RNA -- suggesting they may have been identical until several million years ago. The researchers also solved a long-standing mystery about the O gene, discovering that the gene's inability to produce antigen stems from the lack of a single nucleotide present in the A and B genes. The missing nucleotide causes the O gene to make a protein incapable of marking the cell with an A or B antigen, Hakomori notes.

The team's success in coaxing O blood cells to produce A and B antigens indicates the potential for one day altering a person's blood type, but that possibility "may be down the pike," says hematologist Elizabeth Read of the National Heart, Lung and Blood Institute in Bethesda, Md.

Other applications may prove easier to develop, Hakomori agrees. For example, he notes, epithelial cells normally express the same A, B or O antigens present on blood cells. But in some type O patients with epithelial cell cancers, these cells spontaneously express A or B antigens -- substances that are foreign to the bodies of these individuals and that can trigger an immune response against the cancer cells. Genetic manipulation to selectively enhance the ability of cancer cells to produce these foreign antigens, he says, may stimulate the immune system to eradicate epithelial cancers.

Techniques for accomplishing this goal are not yet available. But a diagnostic procedure using the cloned genes could aid certain cancer patients in the near future, says immunologist Kenneth O. Lloyd of the Memorial Sloan-Kettering Cancer Center in New York City. Compared to currently available assays, such a gene test could more easily identify those patients whose cancers produce foreign blood-type antigens. Physicians might then boost levels of teh appropriate antibodies to battle patients' cancer cells, he adds.

Read notes that the gene cloning may pave the way for identification of other blood-group antigens present on cancer cells, expanding the potential for treatment. Hakomori told SCIENCE NEWS that he and his co-workers are now attempting to clone the gene that codes for a minor blood antigen, called H-Lewis, present on some blood and epithelial cells.