Talk:Trinucleotide repeat disorder

According to my genetics text-book (Thompson & Thomspons, Genetics in Medicine, 2007 pg 388): "...other disorders have now been found to result from the expansion of longer repeats; these include a tetranucleotide (CCTG) in myotonic dystrophy 2 (a close genocopy of myotonic dystrophy 1) and a pentanucleotide (ATTCT) in the spinocerebellar atrophy 10)." So it doesn't just have to be three base pairs. —Preceding unsigned comment added by 151.197.226.243 (talk) 01:03, 9 September 2007 (UTC)

Tetra and penta nucleotide repeat disorders would by definition not be trinucleotide repeat disorders. Friedreich's ataxia is an even longer repeat unit derived from an alu repeat I think.

---

Just a thought, this page could maybe do with some more clarification. Tri nucleotide repeat disorders are implied in the article to occur 'in the gene' coding for the disease related protein. More specifically, its in the promoter region of a gene where this tri-nucleotide repeat occurs. The sequence of the repeat itself isnt usually relevant, except for the fact it contains CpG sequences susceptible to methylation. Methylation of long repeated strands of these repeats causes silencing of the gene, and the associated disease.

---

—Preceding unsigned comment added by 87.194.219.186 (talk) 16:26, 19 October 2007 (UTC)

It isn't always in the promotor region, it's more often in the coding sequence, eg, polyGln disorders. It also doesn't often result in methylation of CpG islands. What you are describing sounds most like how fragile X syndrome works but that isn't a universal mechanism for triplet repeat disorders.

Non-viable di/tetra repeats

Explanation for increased viability of trinucleotide repeats compared to di/tetra repeats lies in that tri nucleotide repeats' extension and contraction does NOT cause FRAMESHIFT while other do. —Preceding unsigned comment added by 89.1.40.121 (talk) 00:54, 10 March 2008 (UTC)

Removed statement that trinucleotide repeat disorders are inherited in "non-mendelian" manner

Trinucleotide disorders, such as Huntington's disease, can be inherited in a mendelian pattern. Fragile X is definitely non-mendelian, but with Huntingonton's it's more complicated. Huntington's can be non-mendelian or mendelian inheritance b/c the repeats can expand during cell cycles, and cross a threshold from silent phenotype to dominant inheritance. So, it's not exactly mendelian, but calling it "non-mendelian" will be confusing to readers without a background in genetics. It would be especially confusing since, in clinical terms, once a disease like Huntington's appears in a family, it will continue to be inherited in a mendelian, autosomal dominant way. So, repeat disease can be mendelian or non-mendelian, depending on the case. Maybe we can work on explaining this, but it might be beyond the scope of the article. Also, the citation for the sentence didn't state that trincleotide repeat disorders are non-mendelian. Txh190 (talk) 1:59, 20 June 2008 (UTC)

Free full text article

Just found this article on polyglutamine aggregation: http://hmg.oxfordjournals.org/cgi/content/full/12/suppl_2/R173. LeeVJ (talk) 11:56, 1 September 2008 (UTC)

ANd this one covers SCA1 to SCA28 and 16q22-linked SCA, ataxia with vitamin E deficiency (AVED), ataxia with oculomotor apraxia type 1 (AOA1), DRPLA, Friedreich ataxia (FRDA) [[1]] LeeVJ (talk) 22:36, 11 March 2009 (UTC)

General Problems

I'm trying not to be overly critical, but I came across this article and am somewhat frustrated. I realize that this is a very large topic, and no article can completely cover everything. I did my Ph.D. dissertation on repeat expansion diseases, so I realize that I might be a lot more picky about some of these things. For this reason I have decided not to attempt to edit this page because: a) I wouldn't know where to start, b) people would probably become frustrated by the amount of detail I would include and consider the article to be "way too much information" (understandably), and c) unfortunately I don't have as much free time as I wish I did to contribute to some of the pages here. In general I think that current and future versions of this article should keep in mind the following considerations (many of which apply in general to any article dealing with any expanding field of knowledge):

Since this is such a large topic, it is unrealistic to expect all of the information to reflect up-to-the-minute developments. Therefore, it is important to stress that the precise mechanisms of how repeat expansions occur are not well understood. Also, for some of the diseases, the mechanisms of how the repeat expansion mutations cause the symptoms of the diseases are not well understood. There are several hypotheses and opposing schools of thought as to how and when the expansion mutations occur in the first place (replication vs. recombination, DNA slippage vs. evasion of DNA repair, or various combinations of these processes and others). You may come across a scientific journal article where the author gives the impression of having the definitive and final answer on these mechanisms. However, it is not uncommon to meet scientists who think they have all the answers to everything -- I happen to work with several of them. But the truth is that we still have much more to learn in this field, so any mention of a particular mechanism should be clarified as being one of the several hypothesis that are still under debate.

While much of the information is outdated and/or incomplete, this is of course to be expected in scientific articles where the field is always expanding. Contributors should be careful to point this out whenever appropriate so that newcomers to the topic will not be led to believe that the statements made are the final word on the topic. I have added links to PubMed and a few other "real-time" resources that would be helpful for those who want more information:

PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). Although many of these articles are highly specialized and probably beyond the scope of what many readers are interested in, there is an option to search for "Review" articles only, and these tend to be a bit more reader-friendly.

National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/disorders/disorder_index.htm). This is a useful resource since many of the repeat expansion diseases are neurological or neuromuscular disorders.

Genetics Home Reference (http://ghr.nlm.nih.gov/). This is maintained by the NIH and National Library of Medicine. Much of the information is written for non-experts, but even as a geneticist I often refer to these pages as a starting point for information on diseases that are outside my area of expertise.

Once again, I don't want to be too critical, but I also think it is important for contributors to keep in mind that many topics in science (and other fields) are constantly changing. It is important to indicate whether or not a topic is still not well understood or is still under debate.