November 16, 2007

Company Offers Genome Assessments



The revolution in human genomics, though barely understood by professionals, is about to hit the street, at least for those able to pay about $1,000 for a glance at their entire genome.


The Icelandic company Decode Genetics announced today that it is launching a service called deCODEme, which will assess a person’s genome for disease risk, bodily traits like hair and eye color, and ancestral origins. Subscribers have to send in a scraping of cells from inside the cheek and a check for $985.


A similar service, using a smaller but custom-made analytic device, is expected to be announced soon by 23andMe, a Google-financed company founded by Linda Avey, a biotechnology executive, and Anne Wojcicki, a health-care investor who is married to Sergey Brin, Google’s co-founder. The 23 in the company’s name refers to the 23 pairs of chromosomes in the human genome.


A third company, Navigenics, of Redwood Shores, Calif., is expected to focus on disease genes.


Unlike the present genetic testing and genetic genealogy companies, which look at a few specific genes, the three new services will sample the whole human genome.


Many people may welcome the rich new trove of data about their hereditary make-up and ancestry, but genetic counselors are concerned that some people may find the information hard to handle, given that much of the current genetic knowledge is related to a person’s risk of developing common and often untreatable diseases.


The new services will use devices known as SNP chips, which offer a cheap substitute for decoding the 3 billion units of the human genome, a task that would probably cost $1 million or so per person at present.


The chips, made by companies like Illumina of San Diego and Affymetrix of Santa Clara, Calif., are programmed to determine the DNA unit at sites along the genome which are known to vary from person to person. The chips thus capture the major points of difference — the single nucleotide polymorphism or “snip” — in an individual’s DNA while ignoring the many sites at which all people have the same DNA unit.


The deCODEme service will use a chip that tests a person’s DNA at one million sites along the genome. The company will then compare this set of data, known as a genotype, with the patients’ genotypes in its own and other databases that have been used in discovering disease-related SNPs. From this comparison the company will estimate a customer’s relative risk of developing the 20 or so common diseases for which disease-related SNPs have been identified.


Decode will also test for genetic variants, discovered by its own and other scientists, that influence the color of a person’s skin, hair and eyes, and whether or not they are prone to freckles.


Besides information about disease risk and normal physiology, Decode will also examine the Y chromosome and mitochondrial DNA, the only two elements of the genome that are always passed down essentially unchanged from one generation to the next. SNPs on the Y chromosome reflect the origin of a man’s ancestors back to 50,000 years ago when modern humans first left their ancestral homeland in northeast Africa. Those on the mitochondrial DNA reflect the wanderings of women throughout the globe.


The significance of most variation in the human genome is presently unknown. Most of the SNPs studied so far have been identified in the course of searching for the genetic roots of common diseases, such as cancer, diabetes and heart disease. Because the diseases are common, many people possess the underlying SNPs. So any interpretation of a person’s genome is at present heavily skewed toward generating ominous news.


This may alarm some customers, even though they will never get most or any of the diseases for which they simply have some genetic risk. There are undoubtedly genes that promote longevity and good health but far fewer of these have yet been spotted. And environmental factors, too, can affect whether certain genes are ever activated.


Genetic counselors have long been concerned that the growing availability of genomic information will outpace the ability to interpret it. Genetic information affects not only the person from whom it is obtained but also their family members. And it cannot ever be changed.


“If people can go into this testing knowing what its limits are, and can take it with a grain of salt, that’s fine,” said Angela Trepanier, incoming president of the National Society of Genetic Counselors. “But you have to be really careful about what you know and don’t know.”


Elizabeth Balkite, a genetic counselor in Durham, N.C., said that “I don’t believe in keeping information from people but I’d be curious as to how useful this would be to the average individual.” If the information is misunderstood, the field will be set back, she said.


Dr. Kari Stefansson, chief executive of Decode Genetics, said the genotyping information his company would provide was not the same as a genetic test. If customers felt they were at particular risk of a disease, they should get a proper test from their physician, he said.


“In our genomes is written the history of our family, the history of our nation and the history of our species,” he said. “People can look at their own genomes and find where your and your family fit into human population history, so I think this is terribly exciting.”


Dr. Stefansson said he genotyped himself and had found disease variants in his own genome, as would be expected since the variants are common.


Decode has genotyped thousands of patients in its search for genetic variants that lie at the roots of common diseases. Dr. Stefansson said this expertise gives the company an advantage over other genotyping services in terms of accuracy, safeguarding privacy, and the ability to interpret the information. 23andMe is using a smaller chip, one with only 650,000 SNPs, he said, although some of the test sites are tailored to generate information about population ancestry.


“They don’t have any track record in human genetics” and will be relying on others to do the genotyping, Dr. Stefansson said.


Ms. Wojcicki said in an email she could not comment on Decode’s announcement because she did not know the details of its service. She declined to elaborate on her own company’s plans.


Dr. Stefansson said that consent forms and other ethical rules drawn up to govern genetic testing in the wake of Nazi experiments were designed to prevent procedures being done on people against their will. But it would be wrongheaded, he said, to prevent people from obtaining information about themselves of their own free will. “The genetic counselors cannot deprive people of the right of genetic self determination,” he said.


In September this year, Craig Venter, the pioneer of decoding genomes, published the almost full sequence of his DNA. But because so little is known about the meaning of variation at each site on the genome, there was not much of interest he could say about himself. Companies like Decode hope that the more people have themselves genotyped, the better they will become at interpreting each DNA difference.


Looking to the day when genomes can be sequenced for just $1,000 or so, the National Society of Genetic Counselors has prepared consumer guidelines that apply to the new genotyping services. Family history is a good guide to disease “and often contains more useful information than full genome sequencing,” the guidelines say. Also, people may find they are at risk for diseases they had not expected, and should consider the impact such findings may have on themselves and their family.