LAUSR

The understanding of human biology and diseases, and the practice (below the threshold for HD) there was an association between CAG reof modernmedicine, is being transformed by genomics. The sequencing of the human genome (from a handful of healthy individuals) almost two decades agowas only a beginning. Over half of the human genome, approximately 3 billion base pairs of DNA, involves repetitive DNA sequences which constitute the repeatome (Hannan, 2012) and could be considered the ‘dark matter’ of the genome. This is because much of it remains under-studied, poorly annotated and functionally mysterious. For large tracts of repetitive sequences within the repeatome, we remain uncertain as to whether they are ‘junk DNA’ (if in fact any part of our genome deserves such a pejorative description) or whether their evolved functions simply remain opaque at this point in time. A key component of the repeatome involves tandem repeats, which constitute over 3% of the human genome. There are over 1.5 million short tandem repeats (STRs), which consist of repeating units of 1–6 basepair motifs of DNA, in the human genome and recent evidence supports their roles in a range of molecular and cellular processes (Gymrek et al., 2016; Hannan, 2018). Whilst the evidence for tandem repeat expansions causing particular Mendelian human disorders has accumulated in the past three decades, the potential roles of tandem repeat polymorphisms (TRPs) in modulating complex human traits and disorders remain largely unexplored (Hannan, 2018). A new article (Lee et al., 2018) in EBioMedicinedescribes a very interesting association between a CAG tandem repeat polymorphism in the huntingtin (HTT) gene and specific measures of cognition (which they refer to as ‘general intelligence’). This work is novel and adds to the rapidly expanding tandem repeat genetics field. The HTT gene first came to prominence 25 years ago, when the CAG repeat, encoding a polyglutamine tract, was found to be expanded in patients with Huntington's disease (HD). However, like many STRs, it is highly polymorphic in the general population, where it may constitute a functional polymorphism. The present study (Lee et al., 2018) involved a cohort of children (6–18 years) at risk of HD and age-matched healthy controls. The most significant aspect of this study is that in the normal range