Genetic Information in Medicine: Its Generation, Significance, and Use

Abstract

“Genetic information” may refer to information about a person’s family history, raw DNA sequence data, or an interpretation derived from the raw data. This chapter addresses what counts as genetic information, with a focus especially on genetic information about humans and the limitations on what can be known.

Family history provides information relating to the risk of specific disease without requiring any DNA sequence data. Another type of indirect genetic information concerns the heritability of quantitative traits and complex disorders; this can demonstrate that genetic factors are involved without specifying precisely what they are.

Genetic linkage studies provide information about the co-localization of a disease-related gene and a nearby marker on a chromosome. Tracking the marker can be used to infer whether someone has inherited the corresponding disorder. In contrast, association studies are performed on large populations and identify many dispersed genetic factors that, jointly and through interactions with the environment, influence the chance of developing the common complex degenerative disorders of Western society. Confidence in the accuracy of individual predictions based on linkage studies is often very high, while genetic association studies provide information that applies robustly to a population but not so readily to making predictions about specific individuals.

The distinction between “raw data” and “interpretation” is unclear and fuzzy. With the high-throughput methods now in use, it is not possible to generate sequence information about a person’s genome – or even a single gene – without an interpretive step based upon sequence information generated earlier from other individuals, which has been accumulated as a body of knowledge. Interpretation by comparison with previous findings will leave some variants as being of uncertain significance (VUSs). This naturally raises the question of future reanalyses and reinterpretations of such VUSs or genome sequence data in general. In addition, unsought information may be found concerning risks of other diseases or of misattributed relationships within a family.

Information concerning many rare disorders has accumulated through a back-and-forth flow of questions and answers between patients/families and clinicians/scientists, to the benefit of both parties.

Ownership of genetic information about individuals’ DNA sequence is probably an unhelpful concept, but control of the uses to be made of such information will be important.

Many ethical questions are raised by developments in DNA sequencing, as it has led to an explosion in the generation of sequence information. These include the information that should be given to a patient about their genome sequence, what information the patient or family should then disclose to relatives, and whether there is an obligation to find out all available information about one’s own genome and then perhaps use it to shape the genome of one’s children.