for $600. however, in 2015 some noted that effective use of whole gene sequencing can cost considerably more than $1000. also, reportedly there remain parts of the human genome that have not been fully sequenced by 2017. comparison with other technologies dna microarrays full genome sequencing provides information on a genome that is orders of magnitude larger than by dna arrays, the previous leader in genotyping technology. for humans, dna arrays currently provide genotypic information on up to one million genetic variants, while full genome sequencing will provide information on all six billion bases in the human genome, or 3,000 times more data. because of this, full genome sequencing is considered a disruptive innovation to the dna array markets as the accuracy of both range from 99.98% to 99.999% (in non-repetitive dna regions) and their consumables cost of $5000 per 6 billion base pairs is competitive (for some applications) with dna arrays ($500 per 1 million basepairs). applications mutation frequencies whole genome sequencing has established the mutation frequency for whole human genomes. the mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation. an even lower level of variation was found comparing whole genome sequencing in blood cells for a pair of monozygotic (identical twins) 100-year-old centenarians. only 8 somatic differences were found, though somatic variation occurring in less than 20% of blood cells would be undetected. in the specifically protein coding regions of the human genome, it is estimated that there are about 0.35 mutations that would change the protein sequence between parent/child generations (less than one mutated protein per generation). in cancer, mutation frequencies are much higher, due to genome instability. this frequency can further depend on patient age, exposure to dna damaging agents (such as uv-irradiation or components of tobacco smoke) and the activity/inactivity of dna repair mechanisms. furthermore, mutation frequency can vary between cancer types: in germline cells, mutation rates occur at approximately 0.023 mutations per megabase, but this number is much higher in breast cancer (1.18-1.66 somatic mutations per mb), in lung cancer (17.7) or in melanomas (≈33). since the haploid human genome consists of approximately 3,200 megabases, this translates into about 74 mutations (mostly in noncoding regions) in germline dna per generation, but 3,776-5,312 somatic mutations per haploid genome in breast cancer, 56,640 in lung cancer and 105,600 in melanomas. the distribution of somatic mutations across the human genome is very uneven, such that the gene-rich, early-replicating regions receive fewer mutations than gene-poor, late-replicating heterochromatin, likely due to differential dna repair activity. in particular, the histone modification h3k9me3 is associated with high, and h3k36me3 with low mutation frequencies. genome-wide association studies main article: genome-wide association study in research, whole-genome sequencing can be used in a genome-wide association study (gwas) – a project aiming to determine the genetic variant or variants associated with a disease or some other phenotype. diagnostic use further information: personal genomics, predictive medicine, and elective genetic and genomic testing in 2009, illumina released its first whole genome sequencers that were approved for clinical as opposed to research-only use and doctors at academic medical centers began quietly using them to try to diagnose what was wrong with people whom standard approaches had failed to help. in 2009, a team from stanford led by euan ashley performed clinical interpretation of a full human genome, that of bioengineer stephen quake. in 2010, ashley's team reported whole genome molecular autopsy and in 2011, extended the interpretation framework to a fully sequenced family, the west family, who were the first family to be sequenced on the illumina platform. the price to sequence a genome at that time was $19,500 usd, which was billed to the patient but usually paid for out of a research grant; one person at that time had applied for reimbursement from their insurance company. for example, one child had needed around 100 surgeries by the time he was three years old, and his doctor turned to whole genome sequencing to determine the problem; it took a team of around 30 people that included 12 bioinformatics experts, three sequencing technicians, five physicians, two genetic counsellors and two ethicists to identify a rare mutation in the xiap that was causing widespread problems. due to recent cost reductions (see above) whole genome sequencing has become a realistic application in dna diagnostics. in 2013, the 3gb-test consortium obtained funding from the european union to prepare the health care system for these innovations in dna diagnostics. quality assessment schemes, health technology assessment and guidelines have to be in place. the 3gb-test consortium has identified the analysis and interpretation of sequence data as the most complicated step in the diagnostic process. at the consortium meeting in athens in september 2014, the consortium coined the word genotranslation for this crucial step. this step leads to a so-called genoreport. guidelines are needed to determine the required content of these reports. genomes2people (g2p), an initiative of brigham and women's hospital and harvard medical school was created in 2011 to examine the integration of genomic sequencing into clinical care of adults and children. g2p's director, robert c. green, had previously led the reveal study — risk evaluation and education for alzheimer's disease – a series of clinical trials exploring patient reactions to the knowledge of their genetic risk for alzheimer's. green and a team of researchers launched the babyseq project in 2013 to study the ethical and medical consequences of sequencing an infant's dna. a second phase, babyseq2, was funded by nih in 2021 and is an implementation study that expands this project, planning to enroll 500 infants from diverse families and track the effects of their genomic sequencing on their pediatric care. in 2018, researchers at rady children's institute for genomic medicine in san diego, ca determined that rapid whole-genome sequencing (rwgs) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. the researchers reported a retrospective cohort study of acutely ill inpatient infants in a regional children's hospital from july 2016-march 2017. forty-two families received rwgs for etiologic diagnosis of genetic disorders. the diagnostic sensitivity of rwgs was 43% (eighteen of 42 infants) and 10% (four of 42 infants) for standard genetic tests (p = .0005). the rate of clinical utility of rwgs (31%, thirteen of 42 infants) was significantly greater than for standard genetic tests (2%, one of 42; p = .0015). eleven (26%) infants with diagnostic rwgs avoided morbidity, one had a 43% reduction in likelihood of mortality, and one started palliative care. in six of the eleven infants, the changes in management reduced inpatient cost by $800,000-$2,000,000. these findings replicate a prior study of the clinical utility of rwgs in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rwgs merits consideration as a first tier test in this setting. a 2018 review of 36 publications found the cost for whole genome sequencing to range from $1,906 usd to $24,810 usd and have a wide variance in diagnostic yield from 17% to 73% depending on patient groups. rare variant association study whole genome sequencing studies enable the assessment of associations between complex traits and both coding and noncoding rare variants (minor allele frequency (maf) < 1%) across the genome. single-variant analyses typically have low power to identify associations with rare variants, and variant set tests have been proposed to jointly test the effects of given sets of multiple rare variants. snp annotations help to prioritize rare functional variants, and incorporating these annotations can effectively boost the power of genetic association of rare variants analysis of whole genome sequencing studies. some tools have been specifically developed to provide all-in-one rare variant association analysis for whole-genome sequencing data, including integration of genotype data and their functional annotations, association analysis, result summary and visualization. meta-analysis of whole genome sequencing studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. some methods have been developed to enable functionally informed rare variant association analysis in biobank-scale cohorts using efficient approaches for summary statistic storage. oncology in this field, whole genome sequencing represents a great set of improvements and challenges to be faced by the scientific community, as it makes it possible to analyze, quantify and characterize circulating tumor dna (ctdna) in the bloodstream. this serves as a basis for early cancer diagnosis, treatment selection and relapse monitoring, as well as for determining the mechanisms of resistance, metastasis and phylogenetic patterns in the evolution of cancer. it can also help in the selection of individualized treatments for patients suffering from this pathology and observe how existing drugs are working during the progression of treatment. deep whole genome sequencing involves a subclonal reconstruction based on ctdna in plasma that allows for complete epigenomic and genomic profiling, showing the expression of circulating tumor dna in each case. ethical concerns the introduction of whole genome sequencing may have ethical implications. on one hand, genetic testing can potentially diagnose preventable diseases, both in the individual undergoing genetic testing and in their relatives. on the other hand, genetic testing has potential downsides such as genetic discrimination, loss of anonymity, and psychological impacts such as discovery of non-paternity. some ethicists insist that the privacy of individuals undergoing genetic testing must be protected, and is of particular concern when minors undergo genetic testing. illumina's ceo, jay flatley, claimed in february 2009 that "by 2019 it will have become routine to map infants' genes when they are born". this potential use of genome sequencing is highly controversial, as it runs counter to established ethical norms for predictive genetic testing of asymptomatic minors that have been well established in the fields of medical genetics and genetic counseling. the traditional guidelines for genetic testing have been developed over the course of several decades since it first became possible to test for genetic markers associated with disease, prior to the advent of cost-effective, comprehensive genetic screening. when an individual undergoes whole genome sequencing, they reveal information about not only their own dna sequences, but also about probable dna sequences of their close genetic relatives. this information can further reveal useful predictive information about relatives' present and future health risks. hence, there are important questions about what obligations, if any, are owed to the family members of the individuals who are undergoing genetic testing. in western/european society, tested individuals are usually encouraged to share important information on any genetic diagnoses with their close relatives, since the importance of the genetic diagnosis for offspring and other close relatives is usually one of the reasons for seeking a genetic testing in the first place. nevertheless, a major ethical dilemma can develop when the patients refuse to share information on a diagnosis that is made for serious genetic disorder that is highly preventable and where there is a high risk to relatives carrying the same disease mutation. under such circumstances, the clinician may suspect that the relatives would rather know of the diagnosis and hence the clinician can face a conflict of interest with respect to patient-doctor confidentiality. privacy concerns can also arise when whole genome sequencing is used in scientific research studies. researchers often need to put information on patient's genotypes and phenotypes into public scientific databases, such as locus specific databases. although only anonymous patient data are submitted to locus specific databases, patients might still be identifiable by their relatives in the case of finding a rare disease or a rare missense mutation. public discussion around the introduction of advanced forensic techniques (such as advanced familial searching using public dna ancestry websites and dna phenotyping approaches) has been limited, disjointed, and unfocused. as forensic genetics and medical genetics converge toward genome sequencing, issues surrounding genetic data become increasingly connected, and additional legal protections may need to be established. public human genome sequences first people with public genome sequences the first nearly complete human genomes sequenced were two americans of predominantly northwestern european ancestry in 2007 (j. craig venter at 7.5-fold coverage, and james watson at 7.4-fold). this was followed in 2008 by sequencing of an anonymous han chinese man (at 36-fold), a yoruban man from nigeria (at 30-fold), a female clinical geneticist (marjolein kriek) from the netherlands (at