Showing posts with label DNA phenotyping. Show all posts
Showing posts with label DNA phenotyping. Show all posts

Tuesday, February 20, 2018

The Face of Genetic Determinism

A press release from KU Leuven (Katholieke Universiteit de Leuven) begins
Our DNA determines what we look like, including our facial features. [T]he potential applications are obvious. In the future, doctors could use DNA for skull and facial reconstructive surgery, forensic examiners could sketch a perpetrator's face on the basis of DNA retrieved from a crime scene, and historians would be able to reconstruct facial features using DNA from days long gone.
These remarks were inspired by a paper in Nature Genetics on "Genome-wide Mapping of Global-to-local Genetic Effects on Human Facial Shape." Genome-wide association studies are notorious for false-positive associations between phenotype and genotype, but the researchers from four universities have reasons to believe that the associations are real. The abstract to the paper, refers not only to replication in an independent sample of 3-D images of faces and genetic data, but also to indications that the genes are active when faces develop in the womb (in the cranial neural crest cells that help to generate most of the distinctive skeletal structures of the head and face):
In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured.
Previous research started with a smaller number of well-defined physical traits, such as the distance between the eyes. But the paper’s lead author, Peter Claes, a postdoctoral researcher in electrical engineering at KU Leuven, said that
Our search doesn't focus on specific traits. My colleagues from Pittsburgh and Penn State each provided a database with 3-D images of faces and the corresponding DNA of these people. Each face was automatically subdivided into smaller modules. Next, we examined whether any locations in the DNA matched these modules. This modular division technique made it possible for the first time to check for an unprecedented number of facial features.
But even if the fifteen associations between a subset of so many "data-driven" facial features and the enormous number of loci across the genome are meaningful, what do they mean for inferring what the face of a person whose DNA is recovered from a crime scene looks like? Although identical twins look very much alike, is the lead line of the reports from the universities’ PR departments that “[o]ur DNA determines what we look like” oversimplified? Another one of the paper’s authors, Mark Shriver, Professor of Anthropology at Penn State, cautioned that
We won't be able to predict a correct and complete face on the basis of DNA tomorrow. We're not even close to knowing all the genes that give shape to our face. Furthermore, our age, environment, and lifestyle have an impact on what our face looks like as well.
Still, Claes is optimistic that the new associations will have practical value in criminal investigations. Seven of the fifteen genes affect the nose, and
A skull doesn't contain any traces of the nose, which only consists of soft tissue and cartilage. Therefore, when forensic scientists want to reconstruct a face on the basis of a skull, the nose is the main obstacle. If the skull also yields DNA, it would become much easier in the future to determine the shape of the nose.
References
  • Peter Claes, Jasmien Roosenboom, Julie D. White, Tomek Swigut, Dzemila Sero, Jiarui Li, Myoung Keun Lee, Arslan Zaidi, Brooke C. Mattern, Corey Liebowitz, Laurel Pearson, Tomás González, Elizabeth J. Leslie, Jenna C. Carlson, Ekaterina Orlova, Paul Suetens, Dirk Vandermeulen, Eleanor Feingold, Mary L. Marazita, John R. Shaffer, Joanna Wysocka, Mark D. Shriver, Seth M. Weinberg. Genome-wide mapping of global-to-local genetic effects on human facial shape. Nature Genetics, 2018; DOI: 10.1038/s41588-018-0057-4
  • Ilse Frederickx (Katrien Bollen transl.), Fifteen New Genes Identified that Shape Our Face, KU Leuven News, Feb. 19, 2018, https://nieuws.kuleuven.be/en/content/2018/fifteen-new-genes-identified-that-shape-our-face
  • Seth M. Weinberg, Making Faces: Diving into the Complex Genetics of Facial Appearance, INSIDE Life Changing Medicine, Feb. 19, 2018, http://insideupmc.upmc.com/complex-genetics-facial-appearance/ (providing a more complete and clearer explanation of the findings than their context than the press releases and news stories)

Monday, January 9, 2017

If You Are Going To Do a “DNA Dragnet,” Cast the Net Widely

Police in Rockingham County, North Carolina, took a circuitous path to identify the killer of a couple who were shot to death in their home in Reidsville, NC. They utilized a “DNA dragnet,” kinship analysis, ancestry analysis, and DNA phenotyping to conclude that the killer was the brother-in-law of the daughter of slain couple. Had the initial DNA collection been slightly more complete, that effort alone would have sufficed.

The evidence that led to the man ultimately convicted of the double homicide were drops of the killer's blood:
Parabon Nanolabs, The French Homicides, Jan. 4, 2017 [hereinafter Parabon]

In the early hours of 4 Feb 2012, Troy and LaDonna French were gunned down in their home in Reidsville, NC. The couple awoke to screams from their 19-year old daughter, Whitley, who had detected the presence of a male intruder in her second floor room. As they rushed from their downstairs bedroom to aid their daughter, the intruder attempted to quiet the girl with threats at knifepoint. Failing this, he released Whitley and raced down the stairs. After swapping his knife for the handgun in his pocket, he opened fire on the couple as they approached the stairwell. During his escape, the perpetrator left a few drops of his blood on the handrail, apparently the result of mishandling his knife. ...
Seth Augenstein, Parabon’s DNA Phenotyping Had Crucial Role in North Carolina Double-Murder Arrest, Conviction, Forensic Mag., Jan. 5, 2017 [hereinafter Augenstein]

A couple were gunned down by an intruder in their North Carolina home in the early hours of Feb. 4, 2012. The teenaged daughter had seen the hooded gunman, when he had briefly held a knife to her throat, but she could apparently not describe him to cops. The attacker left several drops of blood on a handrail as he fled, apparently self-inflicted from his blade.
At a press conference, Sheriff Sam Page announced that "You can run, but you can’t hide from your DNA." Danielle Battaglia, Blood on the Stairs, News & Record Greensboro.com, Apr. 14, 2016 [hereinafter Battaglia]. But efforts to follow the DNA seemed to lead nowhere.
Parabon
Running short of leads, investigators began collecting DNA samples from anyone thought to have been in or around the French home. "We swabbed a lot of people," says Captain Tammi Howell of the RCSO. "Early on, if there was a remote chance someone could have been connected to the crime, we asked for a swab." In the first 12 months following the crime, over 50 subjects consented to provide a DNA sample. None of the samples matched the perpetrator.
Augenstein
"We swabbed a lot of people," said Capt. Tammi Howell, of the Rockingham County Sheriff’s Office, who led the investigation. "Early on, if there was a remote chance someone could have been connected to the crime, we asked for a swab." Those swabs produced no hits.
In particular, this screening of possible sources in the county eliminated "Whitley, her brother, and her boyfriend at the time, John Alvarez." Parabon. But police did not include Alvarez's father or his three brothers in their dragnet search, and when "[a]nalysts uploaded profiles of the blood drops and the skin fragments along with a sample from Whitley French into a database of known samples maintained by the FBI, [t]hey found no match." Battaglia. (According to Forensic Magazine, "the killer was not in any of the public databases," but law enforcement DNA databases are not public.)

There is some confusion in the accounts of what happened next.
Parabon
The first break in the case came when familial DNA testing, performed at the University of North Texas, revealed the possibility that the perpetrator might be related to John Alvarez, Whitley's boyfriend. Because traditional DNA testing is limited in its ability to detect all but the closest relationships (e.g., parent-child), this report alone did not provide actionable information. Subsequently, scientists at the University of North Texas performed Y-chromosome STR analysis, which tests whether two male DNA samples share a common paternal lineage. This analysis, however, showed that the perpetrator did not share a Y-STR lineage with John Alvarez, seemingly eliminating John's father and brother as possible suspects.
Augenstein
Further analysis then indicated that the daughter’s boyfriend, John Alvarez (who had given a swab), could be related to the killer. But it was only a possible relationship, since the STR did not definitively say whether the killer and the boyfriend shared ancestry.
The partial DNA matching led to a Y-STR analysis. The short-tandem repeat on the Y chromosome shows paternal links between fathers, sons and brothers, and has produced huge breakthroughs in cases like the Los Angeles serial killer Lonnie Franklin, Jr., infamously dubbed the “Grim Sleeper.” But in the Sleeper and other cases used “familial searching,” or “FS,” a painstaking and somewhat controversial process of combing large state and national databases like CODIS to find partial DNA matches eventually leading to a suspect. FS was not used in the Rockingham County case, where they had a limited pool of suspects.
Battaglia
Investigators then decided to send the DNA samples out of state for what the warrant called “familial DNA testing,” a type of analysis that allows scientists to match DNA samples to a parent, child or sibling. According to warrants, the samples were sent to the Center for Human Identification at the University of North Texas in Denton. But they do not appear to have gone to that lab. And Rockingham County District Attorney Craig Blitzer said that although a lab did the familial DNA test, it was not North Texas. He declined to say where it was done.
The term "familial searching" has no well-established scientific meaning. As explained in David H. Kaye, The Genealogy Detectives: A Constitutional Analysis of “Familial Searching”, 51 Am. Crim. L. Rev. 109 (2013), kinship testing of possible parents, children, and siblings can be done with the usual autosomal STR loci used for criminal forensic investigation. When this technique is applied to a database (local, state, or national), it sometimes reveals that the crime-scene DNA matches no one in the database but is a near miss to someone -- a near miss in such a way as to suggest the possibility that the source of the crime-scene sample is a brother, son, or parent of the nearly-matching individual represented in the database. In other words, "familial searching" is the process of trawling a database for possible matches to people outside of the database -- "outer-directed trawling," for short.

The Rockingham case evidently involved a conventional but fruitless database search ("inner-directed trawling") followed by testing -- in Texas or somewhere else -- to ascertain whether it was plausible that a close relative of the boyfriend was the source of the blood. Based on the autosomal STRs, this seemed to be the case. However, the laboratory threw a monkey wrench into the investigation when it reported that Y-STRs in the boyfriend's DNA did not match the blood DNA. Because Y-STRs are inherited (usually unchanged) from father to son, this additional finding seemed to exclude the untested father and brothers of the boyfriend.

But the social and familial understanding of a family tree does not always correspond to a biological family tree. It is not unheard of for genetic tests for parentage to reveal unexpected cases of illegitimate children. A man and child who believe that they are father and son may be mistaken. Genetic genealogists like to call the phenomenon of misattributed paternity a Non-Paternity Event, or NPE.

Thinking that the male members of the immediate Alvarez family had to be innocent, police were stymied. They turned to Parabon Nanolabs in Reston, Virginia.
Parabon
[For $3,500, the lab,] starting with 30 ng of DNA, ... genotype[d] over 850,000 SNPs from the sample, with an overall call rate of 98.9% [and advised the police that the blood probably came from a man with] fair or very fair skin, brown or hazel eyes, dark hair, and little evidence of freckling, ... a wide facial structure and non-protruding nose and chin, and ... admixed ancestry, a roughly 50-50 combination of European and Latino ancestry consistent with that observed in individuals with one European and one Latino parent. ... "The Snapshot ancestry analysis and phenotype predictions suggested we should not eliminate José as a suspect, despite the Y-STR results," said Detective Marshall. "The likeness of the Snapshot composite with his driver's license photograph is quite striking."

Augenstein
From approximately 30 nanograms of DNA, the software genotyped approximately 850,000 single-nucleotide polymorphisms, or SNPs, at a call rate of 98.9 percent. In this case, the blood showed the killer to be someone with mixed ancestry – apparently someone with one European and one Latino parent. ... "The Snapshot ancestry analysis and phenotype predictions suggested we should not eliminate Jose (Jr.) as a suspect, despite the Y-STR results," said Det. Marcus Marshall, the lead investigator on the case. "The likeness of the Snapshot composite with his driver’s license photograph is quite striking."
At this time, Parabon proudly juxtaposes the "Snapshot Composite Profile and a photo of José Alvarez, Jr., taken at the time of his arrest" on its website.(and shown below). One of the more intriguing (genetically associated?) similarities is the five o'clock shadow.
Snapshot™ Composite Profile for Case #3999837068, Rockingham County, NC Sheriff's Office

It also would be interesting to know how "confidence" in skin color and other phenotypes is computed. In any event, with this report, police finally obtained DNA samples by consent from the father, José Alvarez Sr., José Alvarez Jr., and Elaine Alvarez, the mother. Analysis indicated misattributed paternity -- and a conventional STR match of the DNA in the bloodstains. As a result,
Parabon
José Alvarez Jr. was arrested on 25 Aug 2015 on two counts of capital murder. He later pled guilty to both murders and on 8 Jul 2016 was sentenced to two consecutive life sentences without the possibility of parole.
Augenstein
Jose Alvarez, Jr., was ... arrested in August 2015 and charged with two counts of capital murder. He later pleaded guilty to killing the Frenches, and was sentenced to two consecutive life sentences without the possibility of parole in July 2016.
A final note on the twists and turns in the case is that John Alvarez's wedding to Whitley French "had been planned for months. Jose Alvarez Jr. served as a groomsman for his brother even as detectives were planning to arrest him on charges that he murdered his new sister-in-law’s parents." Battaglia.

Related posting

"We Can Predict Your Face" and Put It on a Billboard, Forensic Sci., Stat. & L., Nov. 28, 2016

Monday, November 28, 2016

"We Can Predict Your Face" and Put It on a Billboard

An article entitled Craig Venter’s Latest Production (Arlene Weintraub, MIT Technology Review, Sept.-Oct. 2016, at 94) reports that
At Human Longevity Inc. (HLI) in La Jolla, California, more than two dozen machines work around the clock, sequencing one human genome every 15 minutes at a cost of under $2,000 per genome. The whole operation fits comfortably in three rooms. Back in 2000, when its founder, J. Craig Venter, first sequenced a human genome, it cost $100 million and took a building-size, $50 million computer nine months to complete. [¶] Venter’s goal is to sequence at least one million genomes, something that seems likely to take the better part of a decade ...

Seated behind his desk in his office two floors above the sequencing lab, his red poodle Darwin sleeping quietly at his feet, Venter has pulled up images on his computer that show how in one early experiment HLI scientists were able to sequence 1,000 people’s genomes and then reconstruct their faces solely on the basis of the genetic data. “We can predict your face, your height, your body mass index, your eye color, you hair color and texture,” he says, marveling at how closely one of the reconstructed faces matches the photo of the actual study participant.
It would be nice to have a decently designed study of how well all the 1,000 (adult?) faces match the photos. As Richard Feynman once told his students,
The first principle is that you must not fool yourself — and you are the easiest person to fool.
But why wait for whole genome sequencing to "predict" faces? Scores of police agencies already use a different company's product. Parabon Snapshot provides pictures as part of a "scientifically objective description" so "you can conduct your investigation more efficiently and close cases more quickly." Ellen Greytak, director of bioinformatics for Parabon, says that "So far, we've done more than sixty different cases, and we've also done evaluations at the local, state, federal and international levels." In fact, "we've had one conviction and a few other arrests." Michael Roberts, Could DNA Imaging Used in Bennett Family Murder Break JonBenet Case?, Westword, Sept. 16, 2016. Although "none of the police agencies in question has gone public with the technology's role in the cases thus far, she teases that an announcement about a success is pending." Id.

"The composite isn't intended to be like a driver's license photo, but it will bear a resemblance. And if you have a list of 1,000 people who were nearby that day, you can put the ones that match the most at the top, and the ones that match the least at the bottom." Id. (quoting Greytak). Parabon's website explains that this achievement comes from "using deep data mining and advanced machine learning algorithms in a specialized bioinformatics pipeline."

Maybe I missed it, but I saw no references to cross-validation studies of whatever oozed out of the pipeline. Nevertheless, "Snapshot trait predictions are presented with a corresponding measure of confidence, which reflects the degree to which such factors influence each particular trait. Traits, such as eye color, that are highly heritable (i.e., are not greatly affected by environmental factors) are predicted with higher accuracy and confidence than those that have lower heritability; these differences are shown in the confidence metrics that accompany each Snapshot trait prediction."

A "confidence metric" seems to be missing from an unusual advertising campaign called "The Face of Litter" in Hong Kong:
Using the “Snapshot” DNA phenotyping services of a company called Parabon Nanolabs, Ogilvy [a marketing firm] collected litter from the streets and using DNA obtained from the litter, created profiles of the offenders ... . These profiles are now posted on outdoor ads at bus stops, subway and train stations, and even on highway billboards.
Nanalyze, Parabon Nanolabs and DNA Phenotyping, Apr. 30, 2015. Parabon calls this a "social experiment," calling to mind the dismissive remark, "That's not an experiment, it's an experience."

(Last updated 11/29/16)