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Unformatted text preview: P E R S P E C T I V E www. ScienceTranslationalMedicine .org 12 January 2011 Vol 3 Issue 65 65ps2 1 CREDIT: (LEFT PANEL) PHOTOTAKE INC/ALAMY; (RIGHT PANEL) 454 SEQUENCING ROCHE DIAGNOSTICS Th e rapid evolution of molecular technolo- gies to sequence the entire genome of any human has demonstrated extensive genetic variation among all individuals tested. Ap- plication of next-generation sequencing technologies for disease diagnosis and pre- vention could reduce the incidence of del- eterious genetic disorders and improve fetal and neonatal treatments of many conditions. On the other hand, a complete listing of any entire genome will reveal genomic variation that has no clearly interpretable biological, let alone clinical, meaning or application. Broad indiscriminate implementation of evolving genomic technologies, especially for preconception (carrier) and prenatal (fetal) testing for genetic disorders, raises concerns of unintended consequences of our techno- logical triumphs that might undermine their purpose of improving human health. Two studies published in Science Translational Medicine ( 1, 2 ) bring genome sequencing front and center by demonstrating its clini- cal potential in preconception and prenatal genetic testing. Lo et al. ( 1 ) demonstrate the feasibility of using DNA sequences in mater- nal plasma to assemble the fetal genome and to discover in a noninvasive way whether the fetus carries a parental mutation for an in- herited disorder. Meanwhile, Kingsmore and colleagues ( 2 ) combine target gene capture and next generation sequencing to provide a preconception carrier screen for 448 severe recessive childhood diseases. To put these studies in context, we review the history of analyzing the human genome for purposes of informing human reproduction. We then discuss some implications of these new fi nd- ings that raise issues worthy of further study and debate. THE CONTINUED EVOLUTION OF GENETIC TESTING Genetic testing is not new and tracking in- herited characteristics has been practiced for ages, but the application and power of genetic testing has evolved markedly. Simple familial transmission can be followed with ordinary pedigrees to illustrate autosomal dominant and recessive and X-linked inheritance. Even in the absence of laboratory tests, recognition of a signifi cant family history has infl uenced reproductive decisions. Eff orts to apply ge- netic information beyond the family or com- munity have raised controversy or provoked serious consequences as with the early eu- genics movement in the US and the abuses in Germany in the 1930s and 1940s. Technological testing for genetic infor- mation began in the late 1950s with cyto- genetics, perhaps the fi rst useful test for diagnosing multiple signifi cant genetic disorders. Th is led fi rst to the detection of abnormalities of chromosome number (aneuploidy) as in Down syndrome (Fig....
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