The knowledge of one’s personal and familial history — be it genealogical, cultural, or medical — is usually restricted to memories, anecdotes and paper documents. The availability and increasing affordability of DNA sequencing has the potential to change that. Now a multitude of companies are offering to decode your DNA and claiming a crystal ball glimpse into your past, present and future. Are you a descendent of Genghis Kahn? Why does ice-cream cause you pain? Will you develop heart disease? As with any new technology, it can be difficult to decipher what exactly it offers, let alone fully understand the implications of obtaining such information. Do you really want to know your chances of developing cancer? Do the data actually justify being concerned? And will this information be safe from prying eyes? While DNA equals neither identity nor destiny, sequencing can offer a limited but informative glimpse into your genetic make-up.

Not Your Granddaddy’s Mail-Order Kit

Deoxyribonucleic acid (DNA) is the basis of genetic inheritance, and it consists of a combination of four different chemical building blocks called bases that are designated A, T, G and C. Sequencing identifies the patterns of these bases by decoding the order of As, Ts, Gs and Cs within DNA. Every cell within the body contains the same sequences of DNA, but between individuals the sequences are unique.

Personal sequencing kits are offered on-line and in drug stores, but they vary in the kind of technology used, what kind of information is revealed and how much they cost. The simplest and cheapest kits ($100-250), to determine the probability of relatedness between individuals, have traditionally been used for connecting a suspect to a blood sample or determining the paternity of a child. Forensics labs and companies, such as Identigene and HomeDNA, that offer these services utilize the presence of short tandem repeats (STRs) in our DNA. STRs consist of a distinct pattern of DNA bases that is repeated any number of times in a row (ATGC repeated three vs. five times, for example). There are about 10,000 identified STRs in the human genome, but typically only 10-13 are used in tests because of the sheer improbability of any individual (identical twins excluded) having the exact same number of repeats at the same sites.

Kits that decode single nucleotide polymorphisms (SNPs — pronounced “snips”) provide more information. In contrast to STRs, SNPs are differences in single DNA bases (ATGCT instead of ATACT, for example) at specific locations, and there are an estimated 10 million SNPs located within the human genome. The companies that offer this service, such as Ancestry.com and Ethnoacestry.com, sequence a limited number of SNPs known to be specifically inherited from one’s mother or father. Pinpointing a haplogroup (population associated with a specific SNP sequence) can not only identify the relatedness between individuals, but also provide some information as to where one’s ancestors may have originated.

While these tests provide a good general overview of ancestry, they cannot definitively identify relatedness to specific regions or countries of origin. Take an 8% Asian DNA content and connection to the Zulu tribe with a grain of salt. Due in part to migration, the same SNP variants can be present in many different populations, and most databases rely on imperfect statistical estimates because they are based on the sequences of a limited pool of individuals.

Large-Scale Sequencing: GeneChip and BeadChip Technology

For the most in-depth analysis commercially available today, three companies offer the technology that can sequence up to one million SNPs. For $985-2500, 23andMe, deCODE Genetics and Navigenics offer the same Affymetrix GeneChip or Illumina BeadChip technology used in research laboratories. The GeneChip and BeadChip work by adhering millions of small DNA fragments directly to either a quartz wafer or to silica beads embedded on a slide, respectively. These short DNA strands encode the different variants of selected SNPs, which can in turn recognize and bind specific SNPs present in an individual’s DNA. Based on results culled from published studies, the tests will inform if you have SNPs that encode for physical traits such as wet earwax, lactose intolerance and sensitivity to bitter foods. But they will also uncover if your DNA contains SNPs suspected to increase a person’s susceptibility to breast cancer, diabetes and multiple sclerosis.

This vast amount of potentially beneficial information is accompanied by a few precautions. With some exceptions, most complex diseases such as cancer and heart disease are the result of a mixture of different factors (genetics, environment and lifestyle), and sequencing information should not be interpreted as a medical diagnosis of any kind. Clinical knowledge of most individual SNPs is extremely sparse. Regardless, individuals who decide to take advantage of this technology should be prepared to receive information about disease susceptibility and be cautious with respect to how it will be protected from third parties, such as employers and insurance companies. Although genetic counselors and reports detailing the risk each SNP may carry for a particular disease can help interpret sequencing results, science is at the point at which one million SNPs can be identified, but we only know what a small portion of them really mean.

The Future: Personal Genomes for Everyone?

As impressive as the new SNP technologies are, they still only capture a small fraction of variation within the human genome. It is currently feasible to carry out complete genome sequencing, in which all six billion bases of the human genome are decoded. Recently scientists decoded the DNA of Nobel laureate James Watson (who co-discovered the structure of DNA), but it took about two years and 2 million dollars. The X Prize Foundation has issued a challenge to sequence 100 human genomes in 10 days for $10,000 each, in the hope that this technology will someday be affordable to all. Gleaning more meaningful information from sequenced DNA is also a continuing challenge — the letters are legible, but what do they spell? The hope is that while DNA sequences can never be used to unequivocally determine an individual’s health or abilities, it can help tailor specific drugs, medical treatments, and health programs based on a reasonable assessment of risk. And maybe even reveal an ancient Incan princess ancestor.

–Maria Naylor, Harvard Medical School

For More Information:

New York Times: My Genome, Myself: Seeking Clues in DNA:
< www.nytimes.com/2007/11/17/us/17dna.html >

New York Times: DNA Tests Find Branches but Few Roots:
< www.nytimes.com/2007/11/25/business/25dna.html >

Primary Literature:

Science Magazine: The Future of Personal Genomics. Amy L. McGuire, Mildred K. Cho, Sean E. McGuire, and Timothy Caulfield. Sept. 21, 2007. Vol. 231, p1687.

Nature Journal: Common Sense for Our Genomes. Steven E. Brenner. Oct. 18, 2007. Vol. 449, p783-784.