What is personal genomics?
Personal genomics is a branch of genomics.
Personal genomics is of individual genomes are genotyped and analyzed using bioinformatics tools.
Two meanings of personal genomics
Personal genomics has two meanings. One is it aims to sequence everyone on Earth (65 billion people) and it will be done by everyone (common people and companies).
Personal genomics is genome democracy.
Personal genomics is a democratic genomics. It is 1) revolutionary in technology and philosophy 2) done by common people.
It is also related to traditional population genetics. The genotyping stage can have many different experimental approaches including single nucleotide polymorphism (SNP) chips (typically 0.02% of the genome), or partial or full genome sequencing. Once the genotypes are known, there are many bioinformatics analysis tools that can compare individual genomes and find disease association of the genes and loci. The most important aspect of personal genomics is that it may eventually lead to personalized medicine, where patients can take genotype specific drugs for medical treatments.
Personal genomics is not a single individual's vision or invention. Many researchers for decades anticipated this biological branch will eventually arrive with minimum cost of genotyping. Due to the advent of cheap and fast sequencers, full genome personal genomics is becoming a reality. However, there have been active early proponents of personal genomics projects such as George Church in Harvard Medical School.
Genomics used to mean academic research on consensus genomes which have been assembled from many different individuals of a particular species. The personal genomics changes this into customized bioinformatic discovery on individuals.
Use of personal genomics in predictive medicine
Predictive medicine is the use of the information produced by personal genomics techniques when deciding what medical treatments are appropriate for a particular individual.
An example of the use of predictive medicine is pharmacogenomics, in which genetic information can be used to select the most appropriate drug to prescribe to a patient. The drug should be chosen to maximize the probability of obtaining the desired result in the patient and minimize the probability that the patient will experience side effects. It is hoped that genetic information will allow physicians to tailor therapy to a given patient, in order to increase drug efficacy and minimize side effects. There are only a few examples in which this information is currently useful in clinical practice, but it is anticipated that tailored therapy will emerge rapidly as researchers validate the clinical utility of different pharmacogenomic markers.
Another area in which there is great interest is disease risk prediction based on genetic markers. Researchers in this area have generated a great deal of information through the use of genome-wide association studies. While there is hope that risk information will be useful in providing predictive medicine, most common medical conditions are multifactorial and the actual risk to the individual depends on both genetic and environmental components, both of which are not completely understood at present. Therefore, the clinical utility of personal genomic information is currently limited. It is hoped that with further research, an accurate risk profile might enable individuals to take steps to prevent diseases for which they are at increased risk based on genetics.
Cost of sequencing an individual’s genome
There is currently great interest in personal genomics. This is being fuelled by the rapid drop in the cost of sequencing a human genome. This drop in cost is due to the continual development of new, faster, cheaper DNA sequencing technologies such as "next generation DNA sequencing" that may provide access to full genome sequencing so that the entire genetic code of an individual can be deduced all at once.
The National Human Genome Research Institute, part of the U.S. National Institute of Health has set a target to be able to sequence a human-sized genome for US$100,000 by 2009 and US$1,000 by 2014. There is a widespread belief that within 10 years the cost of sequencing a human genome will fall to $1,000.
There are 6 billion base pairs in the diploid human genome. Statistical analysis reveals that a coverage of approximately ten times is required to get coverage of both alleles in 90% human genome from 25 base-pair reads with shotgun sequencing. This means a total of 60 billion base pairs that must be sequenced. An ABI SOLiD, Illumina or Helicos sequencing machine can sequence 2 to 10 billion base pairs in each $8,000 to $18,000 run. The purchase cost, personnel costs and data processing costs must also be taken into account. Sequencing a human genome therefore costs approximately $300,000 in 2008.
In 2009, Complete Genomics of Mountain View announced that it would provide full genome sequencing for $5,000, from June 2009. This will only be available to institutions, not individuals.
This cost is still too high for governments to introduce programs into health services to sequence the genomes of all individuals in a country. However, it may be viable when it falls below $1,000, and the cost of sequencing a human genome is dropping rapidly. For example, approximately 1 million babies are born in Canada each year. To sequence all of their genomes would cost approximately $1 billion per year, or just 1% of Canada’s total healthcare budget. Given the ethical concerns about presymptomatic genetic testing of minors, it is likely that personal genomics will first be applied to adults who can provide consent to undergo such testing.
In June 2009, Illumina announced that they were launching their own Personal Full Genome Sequencing Service at a depth of 30X for $48,000 per genome. This is still too expensive for true commercialization but the price will most likely decrease substantially over the next few years as they realize economies of scale and given the competition with other companies such as Complete Genomics.
Comparative genomics analysis is concerned with characterising the differences and similarities between whole genomes. It may be applied to both genomes from individuals from different species or individuals from the same species, generally at lower cost than sequencing from scratch. In personal genomics and personalized medicine, we are concerned with comparing the genomes of different humans. It is likely that many of the techniques which are developed in comparative genomic analysis will be useful in personal genomics and personalized medicine. This includes rare and common Single nucleotide polymorphisms (consisting substituting one base pair by another, for example CATGCCGG to CATGACGG), as well as insertion or deletion of one or many base pairs.
Predictive medicine services already available
At least four companies which offer genome-wide personal genomics services already have gone to market and are selling their services direct to consumer. They are likely to be the first of many. However, the validity of individual risk predictions based on SNPs and the clinical utility of this information is currently questionable.
- deCODEme.com charges $985 to carry out genotyping of approximately 1 million SNPs and provides risk estimates for 45 diseases as well as ancestry analyses.
- Navigenics, began offering SNP-based genomic risk assessments as of April 2008. Navigenics is medically focused and emphasizes a clinician's and genetic counselor's role in interpreting results. Currently over 20 disease are offered for $2500. . Navigenics uses Affymetrix Genome-Wide Human SNP Array 6.0 , which genotypes 900,000 SNPs. 
- 23andMe sells mail order kits for SNP genotyping. The $399 kit contains everything a patient needs to take their own saliva sample. The patient then mails the sample to 23andMe who carry out microarray analysis on it. This provides genotype information for about 600,000 SNPs. This information is used to estimate the genetic risk of the patient for over 80 diseases as well as ancestry analyses.
- SNPedia is a wiki that collects and shares information about the consequences of DNA variations, and through the associated program Promethease, anyone who has obtained DNA data about themselves (from any company) can get a free, independent report containing risk assessments and related information.
- Bioresolve describes a similar service to that of 23andMe; however, the Better Business Bureau gave them an "F" reliability rating.
- Knome, provides full genome (98% genome) sequencing services for $68,500.
- HelloGene and HelloGenome personal genome information services describe genotyping and full genome sequencing launched by Theragen in Korea. HelloGenome is the first commercial whole genome sequencing service in Asia while HelloGene is the first in Korea. HelloGene uses Affymetrix SNP chips while HelloGenome uses Solexa machines.
- Illumina, Oxford Nanopore Technologies, Sequenom, Pacific Biosciences, Complete Genomics and 454 Life Sciences are companies focused on commercializing full genome sequencing but are not involved in the predictive medicine (interpretative) side.
While personalized medicine will certainly be a great asset to healthcare, it opens up several ethical issues which will need to be thought about carefully. No doubt there will be a huge amount of debate concerning the ethics of personalised medicine in the coming years.
Genetic discrimination is discriminating on the grounds of information obtained from an individual’s genome. Genetic non-discrimination laws have been enacted in most US states and, at the federal level, by the Genetic Information Nondiscrimination Act (GINA). The GINA legislation prevents discrimination by health insurers and employers but does not apply to life insurance or long-term care insurance.
The likelihood of an individual developing breast cancer is affected by which alleles they have of particular genes. Screening can reveal breast cancer in the early stages, allowing it to be successfully treated. 50% of breast cancers occur in the 12% of the population who are at greatest risk. This poses a very difficult question for health services: Is it ethical to deny somebody free screening for a disease if they are genetically at low (but non-zero) risk of developing that disease?
Medical genetics will confront the fact that full sequencing of the genome identifies many polymorphisms that are neutral or harmless. This prospect will create uncertainty in the analysis of individual genomes, particularly in the context of clinical care. Czech medical geneticist Eva Machácková writes: "In some cases it is difficult to distinguish if the detected sequence variant is a causal mutation or a neutral (polymorphic) variation without any effect on phenotype. The interpretation of rare sequence variants of unknown significance detected in disease-causing genes becomes an increasingly important problem."
- Human genome map
- Single nucleotide polymorphism
- Population genomics
- Full Genome Sequencing
- Systems biology
- Population groups in biomedicine
- ^Coming Soon: Your Personal DNA Map?
- ^Table 4. Fractions of Heterozygotes as a function of Shotgun coverage(redundancy)
- ^True Single Molecule Sequencing (tSMS): Helicos BioSciences
- ^ a b Complete Genomics Drives Down Cost of Genome Sequence to $5,000
- ^ McCabe LL, McCabe ER (June 2001). "Postgenomic medicine. Presymptomatic testing for prediction and prevention". Clin Perinatol 28 (2): 425–34. PMID11499063.
- ^ Nelson RM, Botkjin JR, Kodish ED, et al. (June 2001). "Ethical issues with genetic testing in pediatrics". Pediatrics 107 (6): 1451–5. PMID11389275.
- ^ Borry P, Fryns JP, Schotsmans P, Dierickx K (February 2006). "Carrier testing in minors: a systematic review of guidelines and position papers". Eur. J. Hum. Genet. 14 (2): 133–8. doi:10.1038/sj.ejhg.5201509. PMID16267502.
- ^ Borry P, Stultiens L, Nys H, Cassiman JJ, Dierickx K (November 2006). "Presymptomatic and predictive genetic testing in minors: a systematic review of guidelines and position papers". Clin. Genet. 70 (5): 374–81. doi:10.1111/j.1399-0004.2006.00692.x. PMID17026616.
- ^deCODEme, unlock your DNA
- ^Navigenics - Personalized genetic health services
- ^NEJM - Letting the Genome out of the Bottle - Will We Get Our Wish?
- ^23andMe - Our Service: How the Process Works
- ^Knome homepage
- ^Knome FAQ
- ^The DNA Age: Gene Map Becomes a Luxury Item, New York Times, March 2008
- ^"Illumina and Oxford Nanopore Enter into Broad Commercialization Agreement". Reuters. January 12, 2009. http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112. Retrieved February 23, 2009.
- ^"Single Molecule Real Time (SMRT) DNA Sequencing". Pacific Biosciences. http://www.pacificbiosciences.com/index.php?q=technology-introduction. Retrieved February 23, 2009.
- ^"Complete Human Genome Sequencing Technology Overview". Complete Genomics. 2009. http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf. Retrieved February 23, 2009.
- ^ Machácková, Eva, "Disease-causing mutations versus neutral polymorphism: Use of bioinformatics and DNA diagnosis", Cas Lek Cesk (Czech Republic: Ceskoslovenska Lekarska Spolecnost) 142 (3): 150–153