HUMAN GENETICS

Robert Richards (Adelaide Children's Hospital, Australia): "This paper was the first of a series describing the finding of heritable unstable elements in human genetic disease, from our laboratory and those of J.-L. Mandel (Strasbourg, France), C.T. Caskey (Houston), K.H. Fischbeck (Philadelphia), P.S. Harper (Cardiff, England), D.E. Housman (Boston), P. de Jong (Liver- more, Calif.), B. Wieringa (Nijmegen, the Netherlands), and others. Those elements characterized to date are trinucleotide repeats: p(CCG)n for fragile X syndrome (Kremer et al., Science, 252:1711-14, 1991) and p(AGC)n for Kennedy's disease (La Spada et al., Nature, 352:77-9, 1991) and myotonic dystrophy (Brook et al., Cell, 68:799-808, 1992). "The mechanism of mutation of these sequences is novel, since mutability is proportional to their repeat copy number. Therefore, the product of a change in copy number has a different mutation frequency from its predecessor. We have termed this property of heritable unstable elements dynamic mutation— distinct from static ...