The technical artifacts of forensic STR testing: stutter, pull-up, spikes, blobs, and degradation - Jason Gilder, Forensic Bioinformatics



A number of factors can introduce ambiguity into STR evidence, leaving the results open to alternative interpretations. To competently represent an individual incriminated by DNA evidence, defense counsel must uncover these ambiguities, when they exist, understand their implications, and explain them to the trier-of-fact.

Degradation. As samples age, DNA like any chemical begins to break down (or degrade). This process occurs slowly if the samples are carefully preserved but can occur rapidly when the samples are exposed for even a short time to unfavorable conditions, such as warmth, moisture or sunlight.

Degradation skews the relationship between peak heights and the quantity of DNA present. Generally, degradation produces a downward slope across the electropherograms in the height of peaks because degradation is more likely to interfere with the detection of longer sequences of repeated DNA (the alleles on the right side of the electropherogram) than shorter sequences (alleles on the left side).

Degraded samples can be difficult to type. The process of degradation can reduce the height of some peaks, making them too low to be distinguished reliably from background "noise" in the data, or making them disappear entirely, while other peaks from the same sample can still be scored. In mixed samples, it may be impossible to determine whether the alleles of one or more contributors have become undetectable at some loci. Often analysts simply guess whether all alleles have been detected or not, which renders their conclusions speculative and leaves the results open to a variety of alternative interpretations. Further, the two or more biological samples that make up a mixture may show different levels of degradation, perhaps due to their having been deposited at different times or due to differences in the protection offered by different cell types. Such possibilities make the interpretation of degraded mixed sample particularly prone to subjective (unscientific) interpretation.

Spurious Peaks. An additional complication in STR interpretation is that electropherograms often exhibit spurious peaks that do not indicate the presence of DNA. These extra peaks are referred to as "technical artifacts" and are produced by unavoidable imperfections of the DNA analysis process. The most common artifacts are stutter peaks, noise and pull-up.

Stutter peaks are small peaks that occur immediately before (and, less frequently, after) a real peak. Stutter occurs as a by-product of the process used to amplify DNA from evidence samples. In samples known to be from a single source, stutter is identifiable by its size and position. However, it is sometimes difficult to distinguish stutter bands from a secondary contributor in samples that contain (or might contain) DNA from more than one person.

Noise is the term used to describe small background peaks that occur along the baseline in all samples. A wide variety of factors (including air bubbles, urea crystals, and sample contamination) can create small random flashes that occasionally may be large enough to be confused with an actual peak or to mask actual peaks.

Pull-up (sometimes referred to as bleed-through) represents a failure of the analysis software to discriminate between the different dye colors used during the generation of the test results. A signal from a locus labeled with blue dye, for example, might mistakenly be interpreted as a yellow or green signal, thereby creating false peaks at the yellow or green loci. Pull-up can usually be identified through careful analysis of the position of peaks across the color spectrum, but there is a danger that pull-up will go unrecognized, particularly when the result it produces is consistent with what the analyst expected or wanted to find.

Although many technical artifacts are clearly identifiable, standards for determining whether a peak is a true peak or a technical artifact are often rather subjective, leaving room for disagreement among experts. Furthermore, analysts often appear inconsistent across cases in how they apply interpretive standards-accepting that a signal is a "true peak" more readily when it is consistent with the expected result than when it is not. Hence, these interpretations need to be examined carefully.

Spikes, blobs and other false peaks. A number of different technical phenomena can affect genetic analyzers, causing spurious results called "artifacts" to appear in the electropherograms. Spikes are narrow peaks usually attributed to fluctuation in voltage or the presence of minute air bubbles in the capillary. Spikes are usually seen in the same position in all four colors. Blobs are false peaks thought to arise when some colored dye becomes detached from the DNA and gets picked up by the detector. Blobs are usually wider than real peaks and are typically only seen in one color.

Spikes and blobs are not reproducible, which means that if the sample is run through the genetic analyzer again these artifacts should not re-appear in the same place. Hence, the correct way to confirm that a questionable peak is an artifact is to rerun the sample. However analysts, to save time, often simply rely on their "professional experience" to decide which results are spurious and which are real. This practice can be problematic because no generally accepted objective criteria have yet been established to discriminate between artifacts and real peaks (other than retesting).

Threshold Issues: Short Peaks, "Weak" Alleles. When the quantity of DNA being analyzed is very low (as indicated by low peak-heights), the genetic analyzer may fail to detect the entire pro?le of a contributor. Furthermore, it may be dif- ?cult to distinguish true low-level peaks from technical artifacts. Consequently, most forensic laboratories have established peak-height thresholds for "scoring" alleles. Only if the peak-height (expressed in RFU) exceeds a standard value will it be counted.

There are no generally accepted thresholds for how high peaks must be to qualify as a "true allele." Applied Biosystems, Inc., which sells the most widely used system for STR typing (the ABI Prism 310 Genetic Analyzer(tm) with the ProfilerPlus(tm) system) recommends a peak-height threshold of 150 RFU, saying that peaks below this level must be interpreted with caution. However, many crime laboratories that use the ABI system have set lower thresholds (down to 40 RFU in some instances). And crime laboratories sometimes apply their standards in an inconsistent manner from case to case or even within a single case. Hence, a defendant may be convicted in one case based on "peaks" that would not be counted in another case, or by another lab. And in some cases there may be unreported peaks, just below the threshold, that would change the interpretation of the case if considered.

Finding and evaluating low-level peaks can be difficult because labs can set their analytic software to ignore peaks below a specified level and can print out electropherograms in a manner that fails to identify low-level alleles. The best way to assess low-level alleles is to obtain copies of the electronic data files produced by the genetic analyzer and have them re-analyzed by an expert who has access to the analytic software.



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