Ancestry-informative marker

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AIMS can be used to identify five European "clusters" Bauchet European clusters.png
AIMS can be used to identify five European "clusters"

In population genetics, an ancestry-informative marker (AIM) is a single-nucleotide polymorphism that exhibits substantially different frequencies between different populations. A set of many AIMs can be used to estimate the proportion of ancestry of an individual derived from each population.

Contents

A single-nucleotide polymorphism is a modification of a single nucleotide base within a DNA sequence. [1] There are an estimated 15 million SNP (Single-nucleotide polymorphism) sites (out of roughly 3 billion base pairs, or about 0.4%) from among which AIMs may potentially be selected. [2] The SNPs that relate to ancestry are often traced to the Y chromosome and mitochondrial DNA because both of these areas are inherited from one parent, eradicating complexities that come with parental gene recombination. [3] [ page needed ] SNP mutations are rare, so sequences with SNPs tend to be passed down through generations rather than altered each generation. However, because any given SNP is relatively common in a population, analysts must examine groups of SNPs (otherwise known as AIMS) to determine someone's ancestry. Using statistical methods such as apparent error rate and Improved Bayesian Estimate, the set of SNPs with the highest accuracy for predicting a specific ancestry can be found. [4]

Examining a suite of these markers more or less evenly spaced across the genome is also a cost-effective way to discover novel genes underlying complex diseases in a technique called admixture mapping or mapping by admixture linkage disequilibrium.

As one example, the Duffy Null allele (FY*0) has a frequency of almost 100% of Sub-Saharan Africans, but occurs very infrequently in populations outside of this region. A person having this allele is thus more likely to have Sub-Saharan African ancestors. North and South Han Chinese ancestry can be distinguished unambiguously using a set of 140 AIMS. [5]

Collections of AIMs have been developed that can estimate the geographical origins of ancestors from within Europe. [6]

Following the development of ancient DNA databases, ancient ancestry-informative marker (aAIM) were similarly defined as a single-nucleotide polymorphism that exhibits substantially different frequencies between different ancient populations. A set of aAIMs can be used to identify the ancestry of ancient populations and eventually quantify the genetic similarity to modern-day individuals. [7]

Discovery and development

The discovery of ancestry-informative markers was made possible by the development of next generation sequencing, or NGS. NGS enables the study of genetic markers by isolating specific gene sequences. [8] One such method for sequence extraction is the use restriction enzymes, specifically endonuclease, which modifies the DNA sequence. This enzyme can be used with DNA ligase (connecting two different DNA), modifying DNA by inserting DNA from other organism. [9] Another method, cDNA sequencing, or RNA-seq, can also help to acquire information of the transcriptomes in a broad range of organisms and find SNPs (single nucleotide polymorphisms), within a DNA sequence.

Applications

Ancestry informative markers have a number of applications in genetic research, forensics, and private industry. AIMs that indicate a predisposition for diseases such as type 2 diabetes mellitus and renal disease have been shown to reduce the effects of genetic admixture in ancestral mapping when using admixture mapping software. [10] The differential ability of ancestry-informative markers allows scientists and researchers to narrow geographical populations of concern; for example, illegal organ trafficking can be traced to certain areas by comparing the samples taken from organ recipients and deciphering the foreign marker in their body. [11] An array of private companies, such as 23andMe and AncestryDNA, provide cost-effective direct-to-consumers (DTC) genetic testing by analyzing ancestry informative markers to determine geographic origins. These private companies collect massive quantities of data such as biological samples and self-reported information from consumers, a practice known as biobank ing, enabling their researchers to discover more insights on AIMs. [12]

Though AIM panels can be useful for disease screening, the Genetic Information Nondiscrimination Act (GINA) prevents the use of genetic information for insurance and workplace discrimination. [13]

Medical research

Different ancestral traits and their affiliation to diseases can help scientists determine appropriate approaches of treatment for a specific population. [14] Medical researchers have revealed the link between ancestry traits and some common diseases; for example, individuals of African descent have been found to be at higher risk of asthma than those of European ancestry. [15]

AIM panels can be used for detecting disease risk factors. One such panel was created for African American ancestry based on subsets of commercially available SNP arrays. These types of arrays can help reduce the cost of identifying risk factors, since they allow researchers to screen for ancestry markers instead of the entire genome. This is due to the fact that these SNP arrays narrow the scope of the necessary screening from hundreds of thousands of SNP markers to a panel of a few thousands of AIMs. [16]

While some believe that structured populations should be used in studies to better ascertain genetic associations to diseases, the social implications of the potential racial stigma that may result from such studies is a major concern. However, the study done by Yang et al. (2005) suggests that the technology to conduct deeper research into and identify ancestry-associated variations in human disease does already exist. [14]

See also

Related Research Articles

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<span class="mw-page-title-main">Single-nucleotide polymorphism</span> Single nucleotide in genomic DNA at which different sequence alternatives exist

In genetics and bioinformatics, a single-nucleotide polymorphism is a germline substitution of a single nucleotide at a specific position in the genome that is present in a sufficiently large fraction of considered population.

<span class="mw-page-title-main">Haplotype</span> Group of genes from one parent

A haplotype is a group of alleles in an organism that are inherited together from a single parent.

The International HapMap Project was an organization that aimed to develop a haplotype map (HapMap) of the human genome, to describe the common patterns of human genetic variation. HapMap is used to find genetic variants affecting health, disease and responses to drugs and environmental factors. The information produced by the project is made freely available for research.

Researchers have investigated the relationship between race and genetics as part of efforts to understand how biology may or may not contribute to human racial categorization.

A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. It can be described as a variation that can be observed. A genetic marker may be a short DNA sequence, such as a sequence surrounding a single base-pair change, or a long one, like minisatellites.

Genetic association is when one or more genotypes within a population co-occur with a phenotypic trait more often than would be expected by chance occurrence.

<span class="mw-page-title-main">Human genetic variation</span> Genetic diversity in human populations

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.

In molecular biology, SNP array is a type of DNA microarray which is used to detect polymorphisms within a population. A single nucleotide polymorphism (SNP), a variation at a single site in DNA, is the most frequent type of variation in the genome. Around 335 million SNPs have been identified in the human genome, 15 million of which are present at frequencies of 1% or higher across different populations worldwide.

A tag SNP is a representative single nucleotide polymorphism (SNP) in a region of the genome with high linkage disequilibrium that represents a group of SNPs called a haplotype. It is possible to identify genetic variation and association to phenotypes without genotyping every SNP in a chromosomal region. This reduces the expense and time of mapping genome areas associated with disease, since it eliminates the need to study every individual SNP. Tag SNPs are useful in whole-genome SNP association studies in which hundreds of thousands of SNPs across the entire genome are genotyped.

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Diversity Arrays Technology (DArT) is a high-throughput genetic marker technique that can detect allelic variations to provides comprehensive genome coverage without any DNA sequence information for genotyping and other genetic analysis. The general steps involve reducing the complexity of the genomic DNA with specific restriction enzymes, choosing diverse fragments to serve as representations for the parent genomes, amplify via polymerase chain reaction (PCR), insert fragments into a vector to be placed as probes within a microarray, then fluorescent targets from a reference sequence will be allowed to hybridize with probes and put through an imaging system. The objective is to identify and quantify various forms of DNA polymorphism within genomic DNA of sampled species.

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<span class="mw-page-title-main">Restriction site associated DNA markers</span> Type of genetic marker

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Disease gene identification is a process by which scientists identify the mutant genotypes responsible for an inherited genetic disorder. Mutations in these genes can include single nucleotide substitutions, single nucleotide additions/deletions, deletion of the entire gene, and other genetic abnormalities.

Imputation in genetics refers to the statistical inference of unobserved genotypes. It is achieved by using known haplotypes in a population, for instance from the HapMap or the 1000 Genomes Project in humans, thereby allowing to test for association between a trait of interest and experimentally untyped genetic variants, but whose genotypes have been statistically inferred ("imputed"). Genotype imputation is usually performed on SNPs, the most common kind of genetic variation.

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<span class="mw-page-title-main">Polygenic score</span> Numerical score aimed at predicting a trait based on variation in multiple genetic loci

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Human genetic clustering refers to patterns of relative genetic similarity among human individuals and populations, as well as the wide range of scientific and statistical methods used to study this aspect of human genetic variation.

References

  1. ↑ "Polymorphism (genetics)". AccessScience. doi:10.1036/1097-8542.535500.
  2. ↑ Pennisi, Elizabeth (2007). "Human Genetic Variation". Science. 318 (5858): 1842–1843. doi: 10.1126/science.318.5858.1842 . PMID   18096770.
  3. ↑ Houck, Max M; Houck, editor.), Max M; (Firm), ProQuest (2015). Forensic biology. Oxford, England ; San Diego, California : Academic Press. ISBN   9780128007112.{{cite book}}: |first2= has generic name (help)CS1 maint: multiple names: authors list (link)
  4. ↑ Sampson, Joshua N.; Kidd, Kenneth K.; Kidd, Judith R.; Zhao, Hongyu (2011-06-14). "Selecting SNPs to Identify Ancestry". Annals of Human Genetics. 75 (4): 539–553. doi:10.1111/j.1469-1809.2011.00656.x. ISSN   0003-4800. PMC   3141729 . PMID   21668909.
  5. ↑ Qu, Hui-Qi; Li, Quan; Xu, Shuhua; McCormick, Joseph B.; Fisher-Hoch, Susan P.; Xiong, Momiao; Qian, Ji; Jin, Li (2012). "Ancestry Informative Marker Set for Han Chinese Population". G3: Genes, Genomes, Genetics. 2 (3): 339–341. doi:10.1534/g3.112.001941. PMC   3291503 . PMID   22413087.
  6. ↑ Bauchet, Marc; McEvoy, Brian; Pearson, Laurel N.; Quillen, Ellen E.; Sarkisian, Tamara; Hovhannesyan, Kristine; Deka, Ranjan; Bradley, Daniel G.; Shriver, Mark D. (2007). "Measuring European Population Stratification with Microarray Genotype Data". The American Journal of Human Genetics. 80 (5): 948–956. doi:10.1086/513477. PMC   1852743 . PMID   17436249.
  7. ↑ Elhaik, Eran; Pirooznia, Mehdi; Syed, Syakir; Das, Ranajit; Esposito, Umberto (2018-12-12). "Ancient Ancestry Informative Markers for Identifying Fine-Scale Ancient Population Structure in Eurasians". Genes. 9 (12): 625. doi: 10.3390/genes9120625 . PMC   6316245 . PMID   30545160.
  8. ↑ Davey, John W.; Hohenlohe, Paul A.; Etter, Paul D.; Boone, Jason Q.; Catchen, Julian M.; Blaxter, Mark L. (July 2011). "Genome-wide genetic marker discovery and genotyping using next-generation sequencing". Nature Reviews Genetics. 12 (7): 499–510. doi:10.1038/nrg3012. ISSN   1471-0056. PMID   21681211. S2CID   15080731.
  9. ↑ Loenen, Wil A. M.; Dryden, David T. F.; Raleigh, Elisabeth A.; Wilson, Geoffrey G.; Murray, Noreen E. (2013-10-18). "Highlights of the DNA cutters: a short history of the restriction enzymes". Nucleic Acids Research. 42 (1): 3–19. doi:10.1093/nar/gkt990. ISSN   1362-4962. PMC   3874209 . PMID   24141096.
  10. ↑ Keene, Keith L.; Mychaleckyj, Josyf C.; Leak, Tennille S.; Smith, Shelly G.; Perlegas, Peter S.; Divers, Jasmin; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W. (2008-07-25). "Exploration of the utility of ancestry informative markers for genetic association studies of African Americans with type 2 diabetes and end stage renal disease". Human Genetics. 124 (2): 147–154. doi:10.1007/s00439-008-0532-6. ISSN   0340-6717. PMC   2786006 . PMID   18654799.
  11. ↑ Severini, S.; Carnevali, E.; Margiotta, G.; Garcia-González, M.A.; Carracedo, Á. (2015-12-01). "Use of ancestry-informative markers as a scientific tool to combat the illegal traffic in human kidneys". Forensic Science International: Genetics Supplement Series. 5: e302–e304. doi:10.1016/j.fsigss.2015.09.120. ISSN   1875-1768.
  12. ↑ Stoeklé, Henri-Corto; Mamzer-Bruneel, Marie-France; Vogt, Guillaume; Hervé, Christian (2016-03-31). "23andMe: a new two-sided data-banking market model". BMC Medical Ethics. 17 (1): 19. doi: 10.1186/s12910-016-0101-9 . ISSN   1472-6939. PMC   4826522 . PMID   27059184.
  13. ↑ Slaughter (April 25, 2007). "Statement of Administration Policy: Genetic Information Nondiscrimination Act (2007)" (PDF).
  14. 1 2 Yang, Nan; Li, Hongzhe; Criswell, Lindsey A.; Gregersen, Peter K.; Alarcon-Riquelme, Marta E.; Kittles, Rick; Shigeta, Russell; Silva, Gabriel; Patel, Pragna I. (2005-09-29). "Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine". Human Genetics. 118 (3–4): 382–392. doi:10.1007/s00439-005-0012-1. ISSN   0340-6717. PMID   16193326. S2CID   20152083.
  15. ↑ Vergara, Candelaria; Caraballo, Luis; Mercado, Dilia; Jimenez, Silvia; Rojas, Winston; Rafaels, Nicholas; Hand, Tracey; Campbell, Monica; Tsai, Yuhjung J. (2009-03-17). "African ancestry is associated with risk of asthma and high total serum IgE in a population from the Caribbean Coast of Colombia". Human Genetics. 125 (5–6): 565–579. doi:10.1007/s00439-009-0649-2. ISSN   0340-6717. PMID   19290544. S2CID   21141741.
  16. ↑ Tandon, Arti; Patterson, Nick; Reich, David (2010-12-22). "Ancestry informative marker panels for African Americans based on subsets of commercially available SNP arrays". Genetic Epidemiology. 35 (1): 80–83. doi:10.1002/gepi.20550. ISSN   0741-0395. PMC   4386999 . PMID   21181899.
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