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The genotype is the specific genetic makeup (the specific genome) of an individual, in the form of DNA. Together with the environmental variation that influences the individual, it codes for the phenotype of that individual. Non-hereditary mutations are not classically understood as representing the individuals' genotype. Hence, scientists and doctors sometimes talk for example about the (geno)type of a particular cancer, thus separating the disease from the diseased. While codons for different amino acids may change in a random mutation (changing the sequence coding a gene), this doesn't necessarily alter the phenotype.

Typically, one refers to an individual's genotype with regard to a particular gene of interest and, in polyploid individuals, it refers to what combination of alleles the individual carries (see homozygous, heterozygous). Any given gene will usually cause an observable change in an organism, known as the phenotype. The terms genotype and phenotype are distinct for at least two reasons:

  1. To distinguish the source of an observer's knowledge (one can know about genotype by observing DNA; one can know about phenotype by observing outward appearance of an organism).
  2. Genotype and phenotype are not always directly correlated. Some genes only express a given phenotype in certain environmental conditions. Conversely, some phenotypes could be the result of multiple genotypes.

The distinction between genotype and phenotype is commonly experienced when studying family patterns for certain hereditary diseases or conditions, for example, hemophilia. Sometimes people who do not have hemophilia can have children with the disease, because the parents each "carried" hemophilia genes in their body, even though these genes have no effect on the parents health. The parents in this case are called carriers. Healthy people who are not carriers and healthy people who are carriers of the hemophilia gene have the same outer appearance (ie they do not have the disease), therefore they are said to have the same phenotype. However, the carriers have the gene and the other healthy people do not (they have different genotypes).

With careful experimental design, one can use statistical methods to correlate differences in the genotypes of populations with differences in their observed phenotype. These association studies can be used to determine the genetic risk factors associated with a disease. They may even be able to differentiate between populations who may or may not respond favorably to a particular drug treatment. Such an approach is known as personalized medicine.

Inspired by the biological concept and usefulness of genotypes, computer science employs simulated genotypes in genetic programming and evolutionary algorithms. Such techniques can help evolve mathematical solutions to certain types of otherwise difficult problems.