The number of human protein-coding genes is not significantly larger than that of many less complex organisms, such as the roundworm and the fruit fly. This difference may result from the extensive use of alternative pre-mRNA splicing in humans, which provides the ability to build a very large number of modular proteins through the selective incorporation of exons.
Epigenetics describes a variety of features of the human genome that transcend its primary DNA sequence, such as chromatin packaging, histone modifications and DNA methylation, and which are important in regulating gene expression, genome replication and other cellular processes. Epigenetic markers strengthen and weaken transcription of certain genes but do not affect the actual sequence of DNA nucleotides. DNA methylation is a major form of epigenetic control over gene expression and one of the most highly studied topics in epigenetics. During development, the human DNA methylation profile experiences dramatic changes. In early germ line cells, the genome has very low methylation levels. These low levels generally describe active genes. As development progresses, parental imprinting tags lead to increased methylation activity.
The full cost of bringing a new drug (i.e. a drug that is a new chemical entity) to market — from discovery through clinical trials to approval — is complex and controversial. One element of the complexity is that the much-publicized final numbers often do not include just the simple out-of-pocket expenses, but also include «capital costs», which are included to take into account the long time period (often at least ten years) during which the out-of-pocket costs are expended; additionally it is often not stated whether a given figure includes the capitalized cost or comprises only out-of-pocket expenses. Another element of complexity is that all estimates are based on confidential information owned by drug companies, released by them voluntarily. There is currently no way to validate these numbers. The numbers are controversial, as drug companies use them to justify the prices of their drugs and various advocates for lower drug prices have challenged them. The controversy is not only between «high» and «low» — the numbers also vary greatly at the high end.
Many clinical trials do not involve any money. However, when the sponsor is a private company or a national health agency, investigators are almost always paid to participate. These amounts can be small, just covering a partial salary for research assistants and the cost of any supplies (usually the case with national health agency studies), or be substantial and include ’overhead’ that allows the investigator to pay the research staff during times between clinical trials.
In the field of drug discovery, classical pharmacology, also known as forward pharmacology, or phenotypic drug discovery (PDD), relies on phenotypic screening (screening in intact cells or whole organisms) of chemical libraries of synthetic small molecules, natural products or extracts to identify substances that have a desirable therapeutic effect. Using the techniques of medicinal chemistry, the potency, selectivity, and other properties of these screening hits are optimized to produce candidate drugs.
About 8% of the human genome consists of repetitive DNA sequences, termed tandem DNA arrays or tandem repeats. The repeated sequences may be of variable lengths, from two nucleotides to tens of nucleotides. These sequences are highly variable, even among closely related individuals, and so are used for genealogical DNA testing and forensic DNA analysis.
Graduate level programs in medicinal chemistry can be found in traditional medicinal chemistry or pharmaceutical sciences departments, both of which are traditionally associated with schools of pharmacy, and in some chemistry departments. However, the majority of working medicinal chemists have graduate degrees (MS, but especially Ph.D.) in organic chemistry, rather than medicinal chemistry, and the preponderance of positions are in discovery, where the net is necessarily cast widest, and most broad synthetic activity occurs.
For clinical trials involving a seasonal indication (such as airborne allergies, seasonal affective disorder, influenza, and others), the study can only be done during a limited part of the year (such as spring for pollen allergies), when the drug can be tested. This can be an additional complication on the length of the study, yet proper planning and the use of trial sites in the Southern, as well as the Northern Hemisphere allows for year-round trials, which can reduce the length of the studies.
Typically a drug target is a key molecule involved in a particular metabolic or signaling pathway that is specific to a disease condition or pathology or to the infectivity or survival of a microbial pathogen. Some approaches attempt to inhibit the functioning of the pathway in the diseased state by causing target molecule to stop functioning. Drugs may be designed that bind to the active region and inhibit this target molecule. Another approach may be to enhance the normal pathway by promoting specific molecules in the normal pathways that may have been affected in the diseased state. All drugs should also be designed so as not to affect any other important «off-target» molecules or antitargets, since drug interactions with off-target molecules may lead to undesirable side effects. Sequence homology is often used to identify such risks.
The sequencing of the human genome holds benefits for many fields, from molecular medicine to human evolution. The Human Genome Project, through its sequencing of the DNA, can help us understand diseases including: genotyping of specific viruses to direct appropriate treatment; identification of oncogenes and mutations linked to different forms of cancer; the design of medication and more accurate prediction of their effects; advancement in forensic applied sciences; biofuels and other energy applications; agriculture, livestock breeding, bioprocessing; risk assessment; bioarcheology, anthropology, evolution. Another proposed benefit is the commercial development of genomics research related to DNA based products, a multibillion dollar industry.