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Over a million people have taken advantage of direct-to-consumer genetic testing, mostly through the genetic testing company 23andMe. Some are motivated by the desire to know their ancestry, while others hope to gain insight into their disease risks. We are also seeing the launch of dozens of local and international projects that will generate, and hopefully return results of the genome sequences of millions of people. These include efforts by the U.S. Precision Medicine Initiative Cohort, Human Longevity, Inc., the Million Vets Program, Genome England's 100K Genome Project, the Saudi Human Genome Program, and others[1]. It is expected that genome sequencing will become a part of routine health care in the not too distant future. Most of this sequencing will be done on ostensibly healthy individuals. Health care providers need to be aware of the value and limitations of genome sequencing, as they will likely encounter a patient who has this information in hand and asks them what it means. This chapter will help prepare health care providers for a healthy patient coming to them with their genomic information.


Many people who have had their genomes analyzed on the 23andMe targeted genotyping platform think they've had their whole genome sequenced. While they indeed have had many of their variants analyzed, there is a distinction. Figure 11-1 illustrates the difference in the number of nucleotide positions querried by whole genome sequencing, whole exome sequencing, and 23andMe. Both whole-genome sequencing (WGS) and whole-exome sequencing (WES) are designed to detect any of the variants that a person's genome may contain either in their whole genome or only in their exome. In contrast, 23andMe uses a targeted genotyping method where the variants that can be detected have been selected a priori. They include mostly variants in the noncoding (nonexome) region of the genome, along with a select set of exome variants, chosen for their role in disease.

Figure 11-1.

Comparison of nucleotide positions queried by whole-genome sequencing (WGS), whole-exome sequencing (WES), and 23andMe.

Key Point

Both WGS and WES have known gaps in their coverage of certain difficult to sequence gene regions, some of which harbor important disease genes, so in fact “whole” genomes and exomes are not entirely complete with current technology. One study reported that, among 56 important high-risk disease genes, about 10–20% were not adequately covered by WGS[2]. In the diagnostic setting, laboratories often employ enrichment strategies to panels of very important genes to improve the quality of the data. Standard WGS and WES do not employ these tactics.


The ability to glean health information from a genome is determined in part by the platform used to ...

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