Ethical issues raised by common copy number variants and single nucleotide polymorphisms of certain and uncertain significance in general medical practice

摘要

The ethical issues surrounding genotyping for single nucleotide polymorphisms (SNPs) or for copy number variation (CNV) are very different. SNP genotyping can focus on ancestry, risk probability, single gene diagnosis, pharmacogenetics, and carrier testing, and the combination of these in a single test can present difficulties. The interpretation of such tests, inconsistencies between laboratories, and access to genotype information for future reference need to be considered, as well as the value of genotypes of known clinical significance compared with those that provide modest risk modifications with limited potential to take medically useful steps. For CNV genotyping, the major concerns relate to CNVs of uncertain significance and to those with incomplete penetrance. Such CNVs present acute difficulties in counseling symptomatic and asymptomatic individuals and have substantial potential for stigmatization of both groups, as well as raising difficulties when detected in prenatal diagnosis. Improved prenatal diagnosis of many disorders provided by array tests compared with the traditional karyotype probably outweighs the uncertainties for families who would terminate pregnancies with findings associated with severe disabilities. There are substantive concerns about offering SNP or CNV genotyping direct to consumers without a physician or counselor to provide guidance for interpretation of the results.