Human genetic variation is the genetic differences in and among populations. There may be multiple variants of any given gene in the human population (alleles), a situation called polymorphism. 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. Differences between individuals, even closely related individuals, are the key to techniques such as genetic fingerprinting. The human genome has a total length of approximately 3.2 billion base pairs (bp) in 46 chromosomes of DNA as well as slightly under 17,000 bp DNA in cellular mitochondria. In 2015, the typical difference between an individual's genome and the reference genome was estimated at 20 million base pairs (or 0.6% of the total). As of 2017, there were a total of 324 million known variants from sequenced human genomes. Comparatively speaking, humans are a genetically homogeneous species. Although a small number of genetic variants are found more frequently in certain geographic regions or in people with ancestry from those regions, this variation accounts for a small portion (~15%) of human genome variability. The majority of variation exists within the members of each human population. For comparison, rhesus macaques exhibit 2.5-fold greater DNA sequence diversity compared to humans. These rates differ depending on what macromolecules are being analyzed. Chimpanzees have more genetic variance than humans when examining nuclear DNA, but humans have more genetic variance when examining at the level of proteins. The lack of discontinuities in genetic distances between human populations, absence of discrete branches in the human species, and striking homogeneity of human beings globally, imply that there is no scientific basis for inferring races or subspecies in humans, and for most traits, there is much more variation within populations than between them. Despite this, modern genetic studies have found substantial average genetic differences across human populations in traits such as skin colour, bodily dimensions, lactose and starch digestion, high altitude adaptions, drug response, taste receptors, and predisposition to developing particular diseases. The greatest diversity is found within and among populations in Africa, and gradually declines with increasing distance from the African continent, consistent with the Out of Africa theory of human origins. The study of human genetic variation has evolutionary significance and medical applications. It can help scientists reconstruct and understand patterns of past human migration. In medicine, study of human genetic variation may be important because some disease-causing alleles occur more often in certain population groups. For instance, the mutation for sickle-cell anemia is more often found in people with ancestry from certain sub-Saharan African, south European, Arabian, and Indian populations, due to the evolutionary pressure from mosquitos carrying malaria in these regions. New findings show that each human has on average 60 new mutations compared to their parents.
Causes of variation
Causes of differences between individuals include independent assortment, the exchange of genes (crossing over and recombination) during reproduction (through meiosis) and various mutational events. There are at least three 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. A second important process is genetic drift, which is the effect of random changes in the gene pool, under conditions where most mutations are neutral (that is, they do not appear to have any positive or negative selective effect on the organism). Finally, small migrant populations have statistical differences – called the founder effect – from the overall populations where they originated; when these migrants settle new areas, their descendant population typically differs from their population of origin: different genes predominate and it is less genetically diverse. In humans, the main cause is genetic drift. Serial founder effects and past small population size (increasing the likelihood of genetic drift) may have had an important influence in neutral differences between populations. The second main cause of genetic variation is due to the high degree of neutrality of most mutations. A small, but significant number of genes appear to have undergone recent natural selection, and these selective pressures are sometimes specific to one region.
Measures of variation Genetic variation among humans occurs on many scales, from gross alterations in the human karyotype to single nucleotide changes. Chromosome abnormalities are detected in 1 of 160 live human births. Apart from sex chromosome disorders, most cases of aneuploidy result in death of the developing fetus (miscarriage); the most common extra autosomal chromosomes among live births are 21, 18 and 13. Nucleotide diversity is the average proportion of nucleotides that differ between two individuals. As of 2004, the human nucleotide diversity was estimated to be 0.1% to 0.4% of base pairs. In 2015, the 1000 Genomes Project, which sequenced one thousand individuals from 26 human populations, found that "a typical [individual] genome differs from the reference human genome at 4.1 million to 5.0 million sites … affecting 20 million bases of sequence"; the latter figure corresponds to 0.6% of total number of base pairs. Nearly all (>99.9%) of these sites are small differences, either single nucleotide polymorphisms or brief insertions or deletions (indels) in the genetic sequence, but structural variations account for a greater number of base-pairs than the SNPs and indels. As of 2017, the Single Nucleotide Polymorphism Database (dbSNP), which lists SNP and other variants, listed 324 million variants found in sequenced human genomes.
Single nucleotide polymorphisms
… excerpt ends here. Continue reading the full article.
