Personal genomics, a medical revolution!
“I was sitting in front of my brand new iMac, anxiously clicking mouse. My 6-month-old daughter just stopped crying, only after Elizabeth finally came home and started breast-feeding her. Suddenly, a new message popped out. It was from YourGenome@565.com. I opened it immediately.
Thank you for choosing YourGenome Annotation version 4.0 from YourGenome565. Inc. The report contains the complete genome sequence of your daughter. For this matter, you have signed the legal statement that confirms the tissue sample, from which the following sequence was derived, is from a minor who you have complete custody. Hence you will take all responsibility for any legal consequence if the sample was not from the stated donor. We analyzed 5 million single nucleotide polymorphisms (SNP), micro-satellites, inversions, insertions, duplications and translocations with phenotypic associations…
Subject: YourGenome Annotation report version 4.0
Name: Shelly Murphy
Genome ID: 01USANY0F0004222301AUG20ShellyM20150222
Estimated IQ: 135
Analytic and reasoning ability: 95 percentile
Artistic ability: 92 percentile
(Estimated genetic tendency)
BN4 mutations (cartilage development related): negative
BRCA1 mutations (breast cancer related): negative
overall risk for breast cancer: 15% of general population
3. Immune disorders
TREX1 mutations (systemic lupus erythematosus related): negative
overall risk for systemic lupus erythematosus: 9% of general population
10. Age-related diseases
β-amyloid precursor protein (APP) mutations (Alzheimer’s disease related): negative
overall risk for Alzheimer’s disease over 60 years old: 11% of general population
The report was supposed to arrive one month ago, but YourGenome.Inc had informed me that their staffs were overloaded with recent spike on the demand of genome analysis of newborn babies. Such a service had been a private healthcare option for babies for 3 years. But New York state government had made it mandatory 3 months ago after years of legislation on the financial support, database management and legal/ethics regulation. From now on, all new-born New Yorkers would have their unique genome IDs for life. Their health related genetic risks would be regularly updated. The information was encrypted and readily available through a secured government network.
Nevertheless, I was very pleased and relieved. It seemed that my little angel would grow into a smart, beautiful girl and she would unlikely be struck down by breast cancer, heart strike or any nasty autoimmune diseases, nor would she get Alzheimer’s disease, despite of a mildly increased diabetes susceptibility. What if the schools and insurance companies knew some of this information? ‘Quite something…’ I thought. But I knew this could be risky. I need to counsel a lawyer before passing any of her personal genome information to public school or insurance company …” (based on(1))
Personal Genomics- an introduction
Will this fiction become a reality in 2015? Will we predict (to certain extend) a man’s future even before he can speak? Can everyone have his own life decoded and ready at his finger-point? With the blisteringly fast-paced advancement of the biotechnology industry, the answer to these questions seems to be a big YES. Now we all know that DNA is the physical carrier of genetic information. The genome is full set of genes encoding our hereditary information. Wikipedia defines personal genomics as a “branch of genomics where individual genomes are genotyped and analyzed using bioinformatics tools”. Therefore, personal genome is a person’s personal life book, a magical recipe directing two tiny cells, a sperm and an egg, develop into a 50 trillion-cell man with burgeoning intelligence, sensitive emotion and complex social behavior. 2007 saw the birth of personal genomics, which was hailed as the No.1 scientific breakthrough of the year.(2) The huge cost and labor hours of sequencing on large genome used to be the biggest hurdle. But with sequencing technology evolves rapidly, the hurdle is set to be overcome. In 2007, James Watson became the first man who had his entire genome, that is 6 billion nucleotides, sequenced at a cost of US$1.5million in two months, compared to Human Genome Project’s US$2.8 billion over 10 years.(3) Now National Human Genome Research Institute has targeted to sequence a human-sized genome for US$100000 in 2009 and US$1000 in 2014. It is reasonably optimistic to expect that personal genomics, at least the raw sequence, should be within ordinary folk’s means in the near future. Four companies – 23andme, deCODEme, Navigenics and LifeCode have launched commercial personal genome information service (not complete genome sequence though) for as low as US$399. The only private company offering full genome sequencing is Knome based in Cambrige, Massachusetts, which obviously targets a few very rich “elite” clients(4, 5). Now how to efficiently and accurately interpret this 6-billion-letter gene book remains to be a big challenge. Scientists are confident that we are slowly but steadily advance our understanding of human genetics and biology. The above story might seem to be pure fantasy 50 years, now it is becoming a realized miracle. This has been brought about by the advancement of molecular genetics and molecular diagnosis as well as rapidly development of sequencing technology.
Molecular diagnosis utilizes molecular biology technique such as polymerase chain reaction, DNA array, DNA hybridization, etc. to predict disease predisposition, classify clinical diversity and identify the genetic cause for symptoms. It helps physicians prescribe targeted therapy and assess prognosis. With the herald of personal genomics, we are able to gain insight from an individual’s entire genome to find any genetic feature or abnormality. At the same time, molecular genetics studies have provided us ever more detailed knowledge on genetic basis of human biology and disease. From diabetes, hematological leukemia, arthritis(2) to once intractable diseases, such as Parkinson’s disease(6), Alzheimer’s disease(7) have been traced to their genetic basis. Even more remarkably, most of our mental and behavioral trait, including all five basic human personalities have their molecular underpinning(8) and we are finding more and more genetic variants associated with both human physiology and psychology. What’s more, genome information also provide our ancestral information over millions of years. Therefore, we may not only obtain long-dreamed personalized medicine, but also gain a glimpse of our individual biological blueprint and a broad vista encompassing past, present and the future. The impact on human society must be enormous. By early prevention and highly effective treatment, we can dramatically reduced disease prevalence and mortality. Similarly, we can consciously modify our education and social environment to correct, improve or avoid certain propensity, or better fit our personality and talent. Thus, personal genomics has the capacity to greatly benefit us physically as well as mentally by better exploring our potential and also fulfilling our curiosity about ourselves.
As for now, at a price tag of US$300000 to 1million, complete sequencing is still out of reach for most common people. Therefore the services provided by 23andme, deCODEme, Navigenics and LifeCode may be viewed as the precursors for truly personal genomics. Instead of direct sequencing, they all rely on SNP DNA chips to scan up to 1million polymorphism across the entire genome. 1 million SNPs are not limited to just 1 million single nucleotides since certain consecutive SNPs on one chromosome are associated and they normally transmit together. Such an SNP set is called a haplotype. Therefore by identifying limited number of signature SNPs, scientists can cover a relatively larger range on chromosomes by their associated haplotypes. Then they can find disease or any physical and mental trait related polymorphism or haplotypes according to published scientific literature. LifeCode is dedicated to scan cancer related SNPs. The other three also calculate one’s ancestral history from both maternal (mitochondrial DNA) and paternal (Y chromosome DNA) lineage. Among the three pioneering companies, deCODEme provide more disease-specific scan options. Navigenics has the most comprehensive health related analysis and it also offers professional genetic counseling as well as continuous updates for new health predispositions, thus more expensive; whereas 23andme has the most cost-saving choices (as low as US$399). All three set up a customer forum to communicate and share their genetic information at their will.
SNPs don’t account for all the genome variations. Larger changes, such as DNA duplication, translocation, inversion, deletion, insertion, can profoundly change human physiology. For example, certain DNA copy number variations (CNV), which are caused by DNA duplication or deletion, have been shown to correlate with some complicated psychiatric disorder, such as autism and schizophrenia. (9) Given its increased importance, CNV analysis may soon appears on the commercial service lists.
In order to most efficiently utilize this genome information pool, it can be argued to have a government sponsored program to have a large population sequenced. New-born babies could be a candidate. By sequencing their complete genomes, we can gain all genetic information relevant to their future physical and psychological development so that precautions can be implemented accordingly. We can more efficiently obtain new insight about human genetics by cross-examine their genotype and phenotype. These babies will have their genetic book ready for their lifetime. We may expect this will dramatically improve healthcare efficiency and reduce cost. If the National Human Genome Research Institute’s 2014 target can be met, it will be realistic to start such a massive program.
Recreational genomics? Pandora’s box?
Despite of such a promising prospect, not everything is rosy about personal genomics. Immediately following its inception, people have raised practical, ethics and legal concerns. At present, a large number of SNPs have no known disease correlations. Most of customers for the above three companies are well-off persons with strong curiosity to know more about themselves. They are happy to pay to learn some “fun” facts, curly hair, wet ear wax, body odor, male baldness, maverick disposition and so on. Thus, some people dubbed it as “Recreational genomics”(10), a not-very-useful game. But we can argue that even if it mostly gives you such “fun” facts, isn’t it awe to study your characteristics by reading your own genetic book? (Besides, all these are paid by your own money) Just like gazing through your amateur telescope to see the deep universe doesn’t cure your disease or make you a living, but it can be an intellectual inspiration. In addition, with the ever- accelerated medical research advancement, we can expect more and more disease-associated variants will be discovered. So, personal genomics can be an investment for the future. Maybe today’s seemingly useless genome data may turn out to be critically relevant in the future.
Some disease-associated variations only slightly raise risks. In addition, many diseases are determined by multiple factors, so it may be hard to reliably calculate disease susceptibility based on limited number of variants. But one may still get panic once he find he has a SNP related to some horrible diseases, such as Parkinson’s disease, even though that SNP has a weak statistic association. Similarly, genetics heritability for behavioral traits varies wildly, from 65% for dutifulness down to 25% for competence.(11) For example, if someone finds his daughter has several DNA variations associated with neurotic tendency, he might get very upset and overly worried. But the fact is any human social character is molded by both genetic and environmental factors. Education and social interaction can modify or improve any particular trait. In this example, information pointing to neurotic tendency can prompt him to actively device or find relevant programs and social activities for his daughter to avoid such undesirable personality. Therefore, a better public education on human genetics is imperative. On the other hand, we also need oversight on the personal genomics companies to prevent them of misinterpreting the data or overstate their service.
A more serious concern is about people’s privacy and civil right(5, 10). First, we have to ensure any tissue samples submitted are from the one who submits or from a people who he has complete authority. It’s easy to imagine someone may submit his political opponent’s sample to sequence and disclose some unfavorable or embarrassing genetic traits to the public. It will be a severe infringement of privacy. Currently, there is no existing specific law to regulate this identity issue. We need to call on the genome information service industry to beef up self-regulation and expect government legislation body will soon address it. Second, how to address the issue of ownership of the sequence (or any genome analysis data) and how to safeguard it? We have to ensure the customer has the ownership of their genome data and prevent any unauthorized transfer or disclosure of their private information. This, again, awaits new government regulation. Lastly, we need precaution against any discrimination based on genetic screening. The newly enacted Genetic Information Non-discrimination Act (GINA) in the US provides protection from employment and insurance discrimination based on genetic tests. More countries are expected to follow suits. Still we need more vigorous regulation to safeguard people’s privacy. With more people expected to have their personal genome analyzed, a dedicated genomic information agency will be necessary to oversight the personal genomics industry and coordinate the medical utilization of this massive information database. Collaboration and coordination between different countries will also be necessary to ensure people’s private information will not be misused.
In all, without a robust regulation, this nascent discipline risks to become a Pandora’s box. But we can’t afford to throw out the baby along with the bath. We have confidence that we can manage all these potential risks and reap the benefit from decades of scientific research.
Since the birth of molecular biology in 1953 following the discovery of DNA double helix structure, half a century’s biological research culminates in the birth of personal genomics (hence personal medicine is made possible). This is surely a celebration of our scientific achievement. We can envision that in the future, everyone will have his complete genome information at his disposal. A vast personal genome database will be established and managed by government agency to facilitate scientific data mining, medical reference as well as safeguard their holder’s privacy. Invaluable information about his ancestral history, genetic variations will be readily available through internet. Disease prevalence will be dramatically reduced. Social illness due to people’s character defects will also be vastly alleviated. Our intellectual desire to know the nature of life will be greatly satisfied. Hence we may live a longer and happier life. Surely this is the ultimate goal of our science enterprise.