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

Beaudet Genome Medicine 2010, 2:42 /content/2/7/42 CO MMENTA RY Ethical issues raised by common copy number variants and single nucleotide polymorphisms of certain and uncertain signi?cance in general medical practice Arthur L Beaudet* variants (CNVs) in medical practice are su?ciently Abstract di?erent to require separate discussions. e nature of any The ethical issues surrounding genotyping for single nucleotide polymorphisms (SNPs) or for copy number variation (CNV) are very dierent. SNP genotyping can focus on ancestry, risk probability, single gene uncertain signi?cance is somewhat di?erent for SNPs and CNVs. In addition, SNPs can be divided into those known to be associated with single gene disorders and those that can provide risk modi?cation for common diseases. diagnosis, pharmacogenetics, and carrier testing, and the combination of these in a single test can present diculties. 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 signicance compared with those that provide modest risk modications with limited potential to take medically useful steps. For CNV genotyping, the major concerns relate to CNVs of uncertain signicance and to those with incomplete penetrance. Such CNVs present acute diculties in counseling symptomatic and asymptomatic individuals and have substantial potential for stigmatization of both groups, as well as raising diculties 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 ndings associated with severe disabilities. There are substantive concerns about oering SNP or CNV genotyping direct to consumers without a physician or counselor to provide guidance for interpretation of