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