DNA phenotyping

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DNA phenotyping is the process of predicting an organism's phenotype using only genetic information collected from genotyping or DNA sequencing. This term, also known as molecular photofitting, is primarily used to refer to the prediction of a person's physical appearance and/or biogeographic ancestry for forensic purposes.

Contents

DNA phenotyping uses many of the same scientific methods as those being used for genetically informed personalized medicine, in which drug responsiveness (pharmacogenomics) and medical outcomes are predicted from a patient's genetic information. Significant genetic variants associated with a particular trait are discovered using a genome-wide association study (GWAS) approach, in which hundreds of thousands or millions of single-nucleotide polymorphisms (SNPs) are tested for their association with each trait of interest. Predictive modeling is then used to build a mathematical model for making trait predictions about new subjects.

Predicted phenotypes

Human phenotypes are predicted from DNA using direct or indirect methods. [1] With direct methods, genetic variants mechanistically linked with variable expression of the relevant phenotypes are measured and used with appropriate statistical methodologies to infer trait value. With indirect methods, variants associated with genetic component(s) of ancestry that correlate with the phenotype of interest, such as Ancestry Informative Markers, are measured and used with appropriate statistical methodologies to infer trait value. The direct method is always preferable, for obvious reasons, but depending on the genetic architecture of the phenotype, is not always possible. [1]

Biogeographic ancestry determination methods have been highly developed within the genetics community, as it is a key GWAS quality control step. [2] These approaches typically use genome-wide human genetic clustering and/or principal component analysis to compare new subjects to curated individuals with known ancestry, such as the International HapMap Project or the 1000 Genomes Project. Another approach is to assay ancestry informative markers (AIMs), SNPs that vary in frequency between the major human populations. [3]

As early as 2004, evidence was compiled showing that the bulk of phenotypic variation in human iris color could be attributed to polymorphisms in the OCA2 gene. [4] This paper, and the work it cited, laid the foundation for the inference of human iris color from DNA, first carried out on basic level by DNAPrint Genomics [1] Beginning in 2009, academic groups developed and reported on more accurate predictive models for eye color and, more recently, hair color in the European population. [5] [6]

More recently, companies such as Parabon NanoLabs and Identitas have begun offering forensic DNA phenotyping services for U.S. and international law enforcement. [7] [8] However, the science behind the commercial services offered by Parabon NanoLabs has been criticized as it has not been subjected to scrutiny in peer-reviewed scientific publications. It has been suggested that it is not known "whether their ability to estimate a face’s appearance is better than chance, or if it’s an approximation based on what we know about ancestry”. [9]

DNA phenotyping is often referred to as a "biologic witness," a play on the term eye-witness. [10] Just as an eye-witness may describe the appearance of a person of interest, the DNA left at a crime scene can be used to discover the physical appearance of the person who left it. This allows DNA phenotyping to be used as an investigative tool to help guide the police when searching for suspects. DNA phenotyping can be particularly helpful in cold cases, where there may not be a current lead. However, it is not a method used to help incarcerate suspects, as more traditional forensic measures are better suited for this. [11]

Pigmentation Prediction

One online tool available to the public and law enforcement is the HIrisPlex-S Webtool. [12] This system uses SNPs that are linked to human pigmentation to predict an individual's phenotype. Using the multiplex assay described in three separate papers, the genotype for 41 different SNPs can be generated, which are linked to hair, eye and skin color in humans. [13] [14] [6] The genotype can then be entered into the HIrisPlex-S Webtool [12] to generate the most probable phenotype of an individual based on their genetic information.no

This tool originally started as the IrisPlex System, consisting of six SNPs linked to eye color (rs12913832, rs1800407, rs12896399, rs16891982, rs1393350 and rs12203592). [13] The addition of 18 SNPs linked to both hair and eye color lead to the updated HIrisPlex System (rs312262906, rs11547464, rs885479, rs1805008, rs1805005, rs1805006, rs1805007, rs1805009, rs201326893, rs2228479, rs1110400, rs28777, rs12821256, rs4959270, rs1042602, rs2402130, rs2378249 and rs683). [13] Another assay was developed using 17 SNPs involved in skin pigmentation to create the current HIris-SPlex System (s3114908, rs1800414, rs10756819, rs2238289, rs17128291, rs6497292, rs1129038, rs1667394, rs1126809, rs1470608, rs1426654, rs6119471, rs1545397, rs6059655, rs12441727, rs3212355 and rs8051733). [6]

The predictions for eye pigmentation are Blue, Intermediate and Brown. There are two categories for hair pigmentation: color (Blond, Brown, Red and Black) and shade (light and dark). The predictions for skin pigmentation are Very Pale, Pale, Intermediate, Dark and Dark to Black. Unlike eye and hair predictions where only the highest probability is used to make a prediction, the top two highest probabilities for skin color are used to account for tanning ability and other variations.

Genes responsible for facial features

In 2018, researchers found 15 loci in which genes are found that are responsible for our facial features. [15] [16]

Differences from DNA profiling

Traditional DNA profiling, sometimes referred to as DNA fingerprinting, uses DNA as a biometric identifier. Like an iris scan or fingerprint, a DNA profile can uniquely identify an individual with very high accuracy. For forensic purposes, this means that investigators must have already identified and obtained DNA from a potentially matching individual. DNA phenotyping is used when investigators need to narrow the pool of possible individuals or identify unknown remains by learning about the person's ancestry and appearance. When the suspected individual is identified, traditional DNA profiling can be used to prove a match, provided there is a reference sample that can be used for comparison.

Published DNA phenotyping composites

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">Eye color</span> Polygenic phenotypic characteristic

Eye color is a polygenic phenotypic trait determined by two factors: the pigmentation of the eye's iris and the frequency-dependence of the scattering of light by the turbid medium in the stroma of the iris.

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<span class="mw-page-title-main">Sodium/potassium/calcium exchanger 5</span> Protein

Sodium/potassium/calcium exchanger 5 (NCKX5), also known as solute carrier family 24 member 5 (SLC24A5), is a protein that in humans is encoded by the SLC24A5 gene that has a major influence on natural skin colour variation. The NCKX5 protein is a member of the potassium-dependent sodium/calcium exchanger family. Sequence variation in the SLC24A5 gene, particularly a non-synonymous SNP changing the amino acid at position 111 in NCKX5 from alanine to threonine, has been associated with differences in skin pigmentation.

<span class="mw-page-title-main">Ancestry-informative marker</span>

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<span class="mw-page-title-main">DNAPrint Genomics</span>

DNAPrint Genomics was a genetics company with a wide range of products related to genetic profiling. They were the first company to introduce forensic and consumer genomics products, which were developed immediately upon the publication of the first complete draft of the human genome in the early 2000s. They researched, developed, and marketed the first ever consumer genomics product, based on "Ancestry Informative Markers" which they used to correctly identify the BioGeographical Ancestry (BGA) of a human based on a sample of their DNA. They also researched, developed and marketed the first ever forensic genomics product - DNAWITNESS - which was used to create a physical profile of donors of crime scene DNA. The company reached a peak of roughly $3M/year revenues but ceased operations in February 2009.

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References

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  2. ↑ Tian, C.; Gregersen, P. K.; Seldin, M. F. (208). "Accounting for ancestry: population substructure and genome-wide association studies". Human Molecular Genetics. 17 (R2): R143-50. doi:10.1093/hmg/ddn268. PMC   2782357 . PMID   18852203.
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  5. ↑ Walsh, Susan; Liu, Fan; Ballantyne, Kaye N.; van Oven, Mannis; Lao, Oscar; Kayser, Manfred (2011). "IrisPlex: A sensitive DNA tool for accurate prediction of blue and brown eye colour in the absence of ancestry information". Forensic Science International: Genetics. 5 (3): 170–180. doi:10.1016/j.fsigen.2010.02.004. ISSN   1872-4973. PMID   20457092.
  6. 1 2 3 Chaitanya, Lakshmi; Breslin, Krystal; Zuñiga, Sofia; Wirken, Laura; Pośpiech, Ewelina; Kukla-Bartoszek, Magdalena; Sijen, Titia; Knijff, Peter de; Liu, Fan; Branicki, Wojciech; Kayser, Manfred; Walsh, Susan (2018). "The HIrisPlex-S system for eye, hair and skin colour prediction from DNA: Introduction and forensic developmental validation". Forensic Science International: Genetics. 35: 123–135. doi:10.1016/j.fsigen.2018.04.004. hdl: 1805/15921 . ISSN   1872-4973. PMID   29753263. S2CID   21673970.
  7. ↑ Zhang, Sarah (September 22, 2017). "The Genomic Revolution Reaches the City Crime Lab". The Atlantic .
  8. ↑ Curtis, Caitlin; Hereward, James (May 2, 2018). "DNA facial prediction could make protecting your privacy more difficult". The Conversation. Retrieved November 1, 2018.
  9. ↑ Arnold, Carrie (10 September 2020). "The controversial company using DNA to sketch the faces of criminals". Nature News. No. 585. Retrieved 5 April 2021.
  10. ↑ Kayser, Manfred (2015). "Forensic DNA Phenotyping: Predicting human appearance from crime scene material for investigative purposes". Forensic Science International: Genetics. 18: 33–48. doi:10.1016/j.fsigen.2015.02.003. ISSN   1872-4973. PMID   25716572.
  11. ↑ Kayser, Manfred; Schneider, Peter M. (2009). "DNA-based prediction of human externally visible characteristics in forensics: Motivations, scientific challenges, and ethical considerations". Forensic Science International: Genetics. 3 (3): 154–161. doi:10.1016/j.fsigen.2009.01.012. ISSN   1872-4973. PMID   19414162.
  12. 1 2 Dept. of Genetic Information at Erasmus MC. "HIrisPlex-S Eye, Hair and Skin Colour DNA Phenotyping Webtool" . Retrieved 5 April 2021.
  13. 1 2 3 Walsh, Susan; Chaitanya, Lakshmi; Clarisse, Lindy; Wirken, Laura; Draus-Barini, Jolanta; Kovatsi, Leda; Maeda, Hitoshi; Ishikawa, Takaki; Sijen, Titia; de Knijff, Peter; Branicki, Wojciech; Liu, Fan; Kayser, Manfred (2014). "Developmental validation of the HIrisPlex system: DNA-based eye and hair colour prediction for forensic and anthropological usage". Forensic Science International: Genetics. 9: 150–161. doi:10.1016/j.fsigen.2013.12.006. ISSN   1872-4973. PMID   24528593.
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  18. ↑ Cookson, Clive (30 January 2015). "DNA: the next frontier in forensics". Financial Times.
  19. ↑ Kulmala, Teddy (2017-03-30). "Calif. man held in 2011 slayings of Columbia mother and daughter". The State. Retrieved 2018-10-08.
  20. ↑ Snow, Kate (30 June 2015). "Putting a Face to DNA: How New Tech Gives Hope in Cold Cases". NBC Nightly News.
  21. ↑ Haag, Matthew (2018-07-16). "Decades After Killing of April Tinsley, 8, DNA Leads to Suspect". The New York Times. Retrieved 2018-10-04.
  22. ↑ Manning, Johnathan (1 September 2015). "CPSO releases sketch based on DNA sample from cold-case murder". KPLC News.
  23. ↑ Full article on this in National Geographic, July 2016, page 34.
  24. ↑ "Tip from DNA Phenotype 'Snapshot' Leads to Arrest in 2009 Murder Cold Case". Forensic Magazine. 2017-07-25. Retrieved 2018-10-08.
  25. ↑ DeFede, Jim (10 September 2015). "Revolutionary DNA Tech Used to Create 'Serial Creeper' Sketch". CBS Miami.
  26. ↑ Rabin, Charles (23 September 2015). "DNA links 'The Creeper' to sex attack on Miami Beach". Miami Herald.
  27. ↑ Dacey, Kim (3 February 2016). "Police hope composite image can help close cold case". WBAL.
  28. ↑ Shapiro, Emily (2019-07-19). "'People still care': Man murdered in 1960s ID'd through genetic genealogy". ABC News. Retrieved 2019-06-25.
  29. ↑ Glenn, Stacia (6 April 2016). "Tacoma police release composite images of suspects in 1986 slayings". Tacoma News Tribune.
  30. ↑ Murphy, Heather (2018-06-27). "Genealogists Turn to Cousins' DNA and Family Trees to Crack Five More Cold Cases". The New York Times. ISSN   0362-4331 . Retrieved 2019-06-25.
  31. ↑ Glenn, Stacia (2018-06-10). "Another decades-old Tacoma murder solved? Suspected killer of 12-year-old Michella Welch arrested". The News Tribune. Retrieved 2018-10-04.
  32. ↑ Madigan, Michelle (2019-04-05). "The murder of two girls terrified her as a child. So she grew up and tried to find the answers". NBC News. Retrieved 2019-06-25.
  33. ↑ Mikkelsen, Drew (2019-05-23). "Washington's New DNA Law Named for 2 Murdered Tacoma Girls". Forensic Magazine. Retrieved 2019-07-28.
  34. ↑ DeWitt, David (6 April 2016). "Police sharpen image of uptown Athens serial rapist, ask public for help identifying". The Athens News.
  35. ↑ Robinson, Michael (15 April 2016). "New DNA technique could lead to a break in snowbird murder case". The Star.
  36. ↑ Bezaire, Christie (21 April 2016). "Windsor police hope DNA composite profile will help solve 45-year-old murder". CTV News Windsor.
  37. ↑ Culver, David (11 May 2016). "Loudoun County Turns to Composite Image Based on DNA to Crack Cold Case". NBC4 News Washington.
  38. ↑ Towne, Shaun (16 May 2016). "Police release composite of suspect in unsolved Warwick murder". WPRI 12 News.
  39. ↑ Staff Writer (May 3, 2017). "Idaho Falls Police release DNA phenotype of Angie Dodge's murderer". KIFI-TV . Retrieved May 4, 2017.
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