Human genetic variation – Wikipedia, the free encyclopedia

Human genetic variation is the genetic differences both within and among populations. There may be multiple variants of any given gene in the human population (genes), leading to polymorphism. Many genes are not polymorphic, meaning that only a single allele is present in the population: the gene is then said to be fixed.[1] On average, biochemically all humans are 99.9% similar to any other humans.[2]

No two humans are genetically identical. Even monozygotic twins, who develop from one zygote, have infrequent genetic differences due to mutations occurring during development and gene copy number variation.[3] Differences between individuals, even closely related individuals, are the key to techniques such as genetic fingerprinting. Alleles occur at different frequencies in different human populations, with populations that are more geographically and ancestrally remote tending to differ more.

Causes of differences between individuals include the exchange of genes during meiosis and various mutational events. There are at least two reasons why genetic variation exists between populations. Natural selection may confer an adaptive advantage to individuals in a specific environment if an allele provides a competitive advantage. Alleles under selection are likely to occur only in those geographic regions where they confer an advantage. The second main cause of genetic variation is due to the high degree of neutrality of most mutations. Most mutations do not appear to have any selective effect one way or the other on the organism. The main cause is genetic drift, this is the effect of random changes in the gene pool. In humans, founder effect and past small population size (increasing the likelihood of genetic drift) may have had an important influence in neutral differences between populations. The theory that humans recently migrated out of Africa supports this.

The study of human genetic variation has both evolutionary significance and medical applications. It can help scientists understand ancient human population migrations as well as how different human groups are biologically related to one another. For medicine, study of human genetic variation may be important because some disease-causing alleles occur more often in people from specific geographic regions. New findings show that each human has on average 60 new mutations compared to their parents.[4][5] Apart from mutations, many genes that may have aided humans in ancient times plague humans today. For example, it is suspected that genes that allow humans to more efficiently process food are those that make people susceptible to obesity and diabetes today.[6]

Genetic variation among humans occurs on many scales, from gross alterations in the human karyotype to single nucleotide changes.[7]

Nucleotide diversity is the average proportion of nucleotides that differ between two individuals. The human nucleotide diversity is estimated to be 0.1%[8] to 0.4% of base pairs.[9] A difference of 1 in 1,000 amounts to approximately 3 million nucleotide differences, because the human genome has about 3 billion nucleotides.

A single nucleotide polymorphism (SNP) is difference in a single nucleotide between members of one species that occurs in at least 1% of the population. It is estimated that there are 10 to 30 million SNPs in humans.

SNPs are the most common type of sequence variation, estimated to comprise 90% of all sequence variations.[10] Other sequence variations are single base exchanges, deletions and insertions.[10] SNPs occur on average about every 100 to 300 bases [10] and so are the major source of heterogeneity.

A functional, or non-synonymous, SNP is one that affects some factor such as gene splicing or messenger RNA, and so causes a phenotypic difference between members of the species. About 3% to 5% of human SNPs are functional (see International HapMap Project). Neutral, or synonymous SNPs are still useful as genetic markers in genome-wide association studies, because of their sheer number and the stable inheritance over generations.[10]

A coding SNP is one that occurs inside a gene. There are 105 Human Reference SNPs that result in premature stop codons in 103 genes. This corresponds to 0.5% of coding SNPs. They occur due to segmental duplication in the genome. These SNPs result in loss of protein, yet all these SNP alleles are common and are not purified in negative selection.[11]

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Human genetic variation - Wikipedia, the free encyclopedia