One of the most fundamental questions of human existence is, “Why am I the way I am?” For centuries, the traditional answer has been that we are shaped by the families we are born into and the cultures we live in. Science is now giving us a more complex answer, adding another layer to this perpetual mystery: part of who we are lies in our genes.

Until recently, comprehensive analysis of our genes—full genome sequencing and interpretation—has been too costly and too time-consuming, available only to a few. That is now beginning to change. New methods to determine and analyze the full complexity of the human genome are on the horizon, bringing universal genetic testing within reach.

These changes are driven by two major advances. The first is simplified, more affordable technology to read the entire genome . The second is the rise of powerful artificial intelligence systems that can interpret the enormous volume of data generated by sequencing. Together, these advances are opening the door to genetic testing for everyone.

The new technique is called blended genome exome sequencing, or BGE. It reads two views of the DNA in a single sequencing run. One view is a deep read of the small fraction of the genome that codes for proteins, where rare, disease-causing mutations most often lie. The other is a lighter read of the entire remaining genome, where common variants shape day-to-day risk of illness.

Problems in Genetic Screening

For nearly two decades, genetic studies have leaned on a technology called a genotyping array. Arrays are inexpensive. They read a fixed menu of a few hundred thousand pre-selected spots on the genome. These tests are responsible for most of what people now know about the genetics of common diseases.

They carry two large limitations. They see only the spots they were designed to see, and the menus were built largely from studies of people of European descent. Put more simply, they read the DNA of African, Latin American and Asian populations less accurately than they read the DNA of people of European ancestry.

The alternative, deep whole-genome sequencing, reads every letter of the genome many times over. It captures rare mutations, common variants, missing pieces, extra copies and rearrangements. It’s the technology behind newborn screening pilots in the United Kingdom and Florida . It also comes with higher costs.

Most labs have tried to split the difference by sequencing only the protein-coding portion of the genome, called the exome, and pairing that read with a genotyping array. The strategy works, but it produces two datasets that must be knit together by hand. Also, the array half still carries the ancestry bias.

What the Blended Test Does

Blended genome exome sequencing is designed to sidestep that compromise. Every DNA sample is prepared as two libraries in the same laboratory workflow. One part of the DNA sample focuses on only the important protein-coding regions, reading each region 30 to 40 times to find rare changes that might cause disease. The other part takes a quick look across the whole genome, reading each piece only 1 to 4 times. These two sets are then combined and processed in a single test.

The quick look at the whole genome isn’t very detailed on its own. Large reference maps of human DNA help fill in the gaps, so even a shallow read can give a very accurate picture. The results match those of the more expensive, high-detail test over 95 percent of the time for common genetic changes, and over 90 percent of the time for less common ones.

The detailed look at the protein-coding regions is good enough on its own to spot rare, important changes. Since both parts come from the same sample and are tested together, the results are automatically matched up and easy to use. This method can also spot larger changes—such as missing or extra chunks of DNA—that older, cheaper tests can’t detect. In a study of children with autism, the new method found all the same important DNA changes as the more expensive, traditional test.

From Discovery to the Clinic

The value of a cheaper genome does not stop in the research setting. A version of the test tuned for clinical use is now the basis of a genetic test for people at risk of prostate cancer, one of the most common cancers in the world. Wider clinical uses are already in development.

A person’s genome is a rich source of information about their future health, and knowing that information early enough to act on it changes lives. Therefore, this benefit must reach everyone, not only those whose ancestors match the reference sets from past decades. Blended genome exome sequencing captures the same broad range of information as deep whole-genome sequencing, including rare protein-changing mutations, common variants and structural rearrangements.

The cost wall that has kept universal genome reading a promise rather than a practice looks a little lower now. As technology continues to improve, the day when every newborn's genome can be read at birth and every adult's genome can be read on request draws closer.