Lost in the Junk

Today, New York Times reporter Gina Kolata reported that “Reanimated ‘Junk’ DNA Is Found to Cause Disease” [1]. The research paper in question [2] does not refer (in so many words) to “junk DNA,” for this term no longer is in vogue among geneticists. But the paper does identify the role of a pseudogene within a macrosatellite in causing a common form of muscular dystrophy (known as FSHD). (See also [3].)

I mention the article because of the legal literature and courtroom testimony on “junk DNA.” Some lawyers, judges, sociologists, and advocacy groups maintain that because parts of what once was called “junk DNA” are functional, it follows that the nonfunctional DNA sequences used for criminal identification databases could well be used to diagnose or predict disease status. Will this new discovery soon be cited as supporting this possibility? I hope not, because the discovery has little bearing on the privacy implications of forensic STR profiling.

Elsewhere, I have shown that the concern over medical utility of the forensic STRs ignores biologically important distinctions among different types of noncoding DNA [4, 5]. The fear is based on the following sort of argument:

  1. Some noncoding DNA has diagnostic or predictive utility.
  2. The STRs used for identification are noncoding.
  3. Therefore, the STRs used for identification have diagnostic or predictive utility.

Of course, one could just as well argue that

  1. Some mammals are vampire bats.
  2. Humans are mammals.
  3. Therefore, humans are vampire bats.

It takes a more discerning analysis of the larger category (noncoding DNA or mammals) to make a meaningful risk assessment. Let’s see how this plays out here.

That a pseudogene is involved in the development of muscular dystrophy is an exciting discovery with immediate implications for research into other diseases. Apparently, the pseudogene is not entirely inactive. Indeed, it is an open reading frame that always is transcribed into RNA, but ordinarily the transcripts are not stable. FSHD patients, however,

carry specific single nucleotide polymorphisms (SNPs) in the chromosomal region distal to the last D4Z4 repeat. This FSHD-predisposing configuration creates a canonical polyadenylation signal for transcripts derived from DUX4, a double homeobox gene of unknown function that straddles the last repeat unit and the adjacent sequence. … DUX4 transcripts are efficiently polyadenylated and are more stable when expressed from permissive chromosomes [those with the right SNPs]. These findings suggest that FSHD arises through a toxic gain of function attributable to the stabilized distal DUX4 transcript. [2]

Let’s translate this into less technical language. Within a cell, the information in a gene gets “transcribed” into another molecule (RNA) and then translated into proteins. The “wrong” proteins can cause muscular dystrophy. A remnant of a gene on the fourth largest chromosome still contains instructions for a cell to make a protein, and these still get transcribed into the RNAs. But normally the RNAs do not get translated into proteins because they fall apart fairly quickly. However, certain mutations elsewhere on the same chromosome cause the RNAs to become stable. Those stabilized RNA are translated into the proteins resulting in the disease. In short, the “junk DNA” is a gene that still produces transcripts, but the transcripts are not functional in most people.

In contrast, the microsatellites (STRs) used in forensics do not produce transcripts. Therefore, they cannot have the same effects as the DUX4 pseudogenes that do. The colorful writing about reanimating “junk” DNA notwithstanding, the recent findings about the D4Z4 macrosatellite cannot support the argument that forensic STR profiles are a real threat to medical privacy.

This does not mean that it impossible that the STR profiles could not have some role in bodily functioning and health. The human geneticists I have consulted do not see how this could be, but other geneticists have warned me not to rule it out. Fifty years from now, they say, we’ll know more than we do now. Of course, even if the STRs do something in some situations, this does not mean that the features of the STRs used for identification will have any medical significance.


1. Gina Kolata, Reanimated ‘Junk’ DNA Is Found to Cause Disease, N.Y. Times, Aug. 19, 2010

2. Richard J. L. F. Lemmers, Patrick J. van der Vliet, Rinse Klooster, Sabrina Sacconi, Pilar Camano, Johannes G. Dauwerse, Lauren Snider, Kirsten R. Straasheijm, Gert Jan van Ommen, George W. Padberg, Daniel G. Miller, Stephen J. Tapscott, Rabi Tawil, Rune R. Frants, and Silvere M. van der Maarel, A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy,” Science DOI: 10.1126/science.1189044, Aug. 19, 2010,

3. National Institute of Neurological Disorders and Stroke (NINDS), Discovery Opens Door to Therapeutic Development for FSH Muscular Dystrophy, NIH News, Aug. 19, 2010, http://www.nih.gov/news/health/aug2010/ninds-19.htm

4. D.H. Kaye, Science Fiction and Shed DNA, 101 Nw. U. L. Rev. Colloquy 62 (2006), http://www.law.northwestern.edu/lawreview/colloquy/2006/7/

5. D.H. Kaye, Please, Let’s Bury the Junk: The CODIS Loci and the Revelation of Private Information, 102 Nw. U. L. Rev. Colloquy 70 (2007), http://www.law.northwestern.edu/lawreview/colloquy/2007/25/