Huntingtin and Huntington's Disease

The following is a review of the original scientific paper highlighting the discovery of the gene implicated in Huntington's disease.  A discussion of a popular press article which reviews this research can be found here.  A comparison between the two papers can be found here. 

I analyzed two articles on the discovery of the Huntington’s disease protein, one a popular press article in the New York Times by Natalie Angier, and the other the primary research paper written by the Huntington’s Disease Research Group

The research paper produced by the Huntington’s  Disease Collaborative Research Group in 1993 highlights the detection and characterization of the gene responsible for Hungtington’s Disease, described as IT15 in the paper.  The paper represents a major breakthrough in research related to Huntington’s Disease and provided the basis of future investigations of the disease on a molecular level.   Here I make an analysis of the research paper. 

The introduction provides a limited set of background details on Hungtinton’s Disease, essentially enough to quickly refresh the reader of major details of the disease.  A general background  on the nature of Huntington’s  is assumed by the authors.   The introduction serves to both highlight past research made in the detection of the Huntington’s disease gene and to provide rationale for the current experiment.  The authors accomplish this in direct, step by step descriptions of the relevant prior research, demonstratred in a linear manner.  The experimental strategy is also described, to a limited amount of detail.  The authors note the validity of their exon amplification technique as a manner of obtaining gene sequences.

The results section outlines the different experiments conducted and the reasoning behind each method.  The first step the authors made was to determine the specific location of the gene through the exon amplification technique.  The general location of the gene on the chromosome was known and well characterized, according to the authors, so the exon amplification technique served to specifically identify the exact location of the HD gene, IT15.  The identified gene and protein sequences were produced in its entirety in the paper, spanning two full pages.   Next, the authors searched for polymorphisms in the CAG repeat portion of the gene to link the genetic information to the disease.  This was conducted by PCR of known Huntington’s Disease patients.  After finding the number of CAG repeats to be vastly increased in Huntington’s Disease patients, the authors attempted to determine the relative stability of expansion.  This data led to the attempted determination of whether a CAG repeat mutation led to new instances of Huntington’s Disease.

The discussion section provides an overview of the results and their relevance to both future research and the current diagnostic procedures for Huntington’s Disease.  The authors stress the mechanism in which the protein actually leads to the disease.  The authors indicate this mechanism is of great importance, since other similar diseases.  The future of research into the disease is also discussed, highlighting the potential of the data gained from these findings as a diagnostic tool, as well as the link between CAG repeat quantity and age of onset.

The paper provided an excellent presentation of an important research breakthrough.  I thought the linear, stepwise rational and background information given in the introduction provided  a comprehensive overview of the research steps taken to reach the current state of understanding on Huntingotn’s.   In this manner, the current research was presented as a step, albiet a large one, in the process of discovering the cause of Hungtington’s Disease.   In the discussion, the reader is informed by the authors of possible future directions in research on the gene IT15.  Thus, the reader develops the sense of the discovery as a link in a longer chain of events necessary to characterize and, eventually, treat Huntington’s Disease.  Finally, returning to the results section, the figures and descriptions of experiments place a large amount of focus demonstrating evidence for the validity of their methods.  In this manner, after reading the paper, the reader is likely to be thoroughly convinced the findings presented in the paper are valid. 



MacDonald, Ambrose, Duyao, Myers, Lakshmi Srinidhi, Barnes, Taylor, James, Groot, MacFarlane, Jenkins, Anderson, Wexler, Gusella, Bates, Baxendale, Hummerich, Kirby, North, Youngman, Mott, Zehetner, Sedlacek, Poustka, Frischauf, Lehrach, Buckler, Church, Doucette-Stamm, O'Donovan, Riba-Ramirez, Shah, Stanton, Strobel, Draths, Wales, Dervan, Housman, Altherr, Shiang, Thompson, Fielder, Wasmuth, Tagle, Valdes, Elmer, Allard, Castilla, Swaroop, Blanchard, Collins, Snell, Holloway, Gillespie, Datson,  Shaw, Harper. 1993.  "A Novel Gene Containing a Trinucleotide Repeat That Is Expanded and Unstable on Huntington’s Disease Chromosomes."  Cell Volume72, Issue 6, p. 971-983.  doi:10.1016/0092-8674(93)90585-E