AGAPE

  • AddThis Feed Button
  • Calendar

    July 2007
    M T W T F S S
    « Jun   Aug »
     1
    2345678
    9101112131415
    16171819202122
    23242526272829
    3031  
  • Add to Technorati Favorites
  • Archives

  • Top Posts

  • Blog Stats

    • 26,010 hits
  • Flickr Photos

    Harlaxton Manor

    25 Panorama - Explored

    ...and the livin' is easy

    More Photos
  • Recent Comments

    RadWind on Physical biology
    iskanbasal on Babinski sign
    Jacek on Babinski sign
    drtombibey on Jill Bolte Taylor: My stroke o…
    Emma Jones on PFO Closure has significant im…
    Variability is the l… on A new, precise definition of a…
    Kesington on Biology on Physical biology
  • Top Clicks

    • None
  • Delicious

  • TAGS

  • AddThis Social Bookmark Button
  • visitors

WHY A GENETIC DEFECT PRESENT AT BIRTH MANIFESTS IN DISEASE ONLY LATER IN LIFE?

Posted by iskanbasal on July 6, 2007

Few years ago I asked this Q to a scientist at ASK THE SCIENTIST section somewhere. The scientist gave this answer that I feel very instructive and I like to keep here in my diary of posts.

When an individual inherit a genetic deficit they have it since their birth, take for example those that underlie muscular dystrophies such as myotonic dystrophy or dystrophinopathies. There is a normal tissue formation and function for a different number of years before the deficit show itself with a disease that destroy the already normally formed tissue. I’d like to know why such deficit did not interfere during the tissue formation disrupting it? Thank you.

This is a fascinating question. In fact, there are at least two related issues to consider here. The first involves the very interesting observation that gene products can have quite different roles during embryogenesis, or development, on the one hand; and when the organism is fully formed, on the other. Some good examples of this can be seen in experimental models (Mice), where a gene that, in the adult stage, seems to have a fairly limited and non-essential role, is knocked out of an emrboyonic animal. Often, we find that the knock-out is unable to survive. But your question is different, in that the defect exists at birth, but only manifests in disease later in life. There are a few explanations for this, which I’ll describe briefly. Then I’ll tell you about one specific hypothesis that has been advanced in explanation of what we see in myotonic dystrophy.So briefly, a genetic defect can cause symptoms later in life, under a number of conditions: 1. Consider that the body is in constant change, with regard to the ‘balance’ of hormones, and other important proteins, which are dominant at any given stage in life. So, even if a person is pre-disposed to certain diseases, they may be “protected” by other biological factors, until that balance shifts due to puberty, menopause etc. 2. The role for environmental factors cannot be overstated; included here are things like infections, poverty, nutrition, chemical exposure, radiation and so on. These may all trigger an underlying pre-disposition which is genetic in origin.Myotonic dystrophy is interesting in that the genetic defect is dominant, that is, one needs only one “allele” of the defective dystrophin gene in order to be affected. Also, the diseaese often is worse from one generation to the next. This phenomenon has been attributed to the way the genetic defect actually expands, in the form of “tri-nucleotide repeats,” which are described as “CUG repeats.” One explanation for why the disease manifests in symptoms only later in life has to do with the activity of another protein, which usually assists in the protein production of other genes. This protein, known as CUG-BP, or “CUG- Binding Protein” is actually attracted to these CUG repeats. As more and more CUG’s appear in the nucleus, more of this important protein is distracted from helping other genes, and becomes bound to the CUG’s that have been incorporated into the Dystrophin gene.As time goes on, there may be a lack of important proteins being produced, due to this defect. One example, reported upon in 1998, is that of an important cardiac protein, Troponin I. I will attach the abstract from that paper, below, in case you are interested. It was published in the journal Science.

Hope that is helpful!

Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy.Philips AV, Timchenko LT, Cooper TA.Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.Myotonic dystrophy (DM) is caused by a CTG expansion in the 3′ untranslated region of the DM gene. One model of DM pathogenesis suggests that RNAs from the expanded allele create a gain-of-function mutation by the inappropriate binding of proteins to the CUG repeats. Data presented here indicate that the conserved heterogeneous nuclear ribonucleoprotein, CUG-binding protein (CUG-BP), may mediate the trans-dominant effect of the RNA. CUG-BP was found to bind to the human cardiac troponin T (cTNT) pre-messenger RNA and regulate its alternative splicing. Splicing of cTNT was disrupted in DM striated muscle and in normal cells expressing transcripts that contain CUG repeats. Altered _expression of genes regulated posttranscriptionally by CUG-BP therefore may contribute to DM pathogenesis

About these ads

One Response to “WHY A GENETIC DEFECT PRESENT AT BIRTH MANIFESTS IN DISEASE ONLY LATER IN LIFE?”

  1. [...] And an other interesting essay on an important question: Why a genetic defect present at birth manifests in disease only in later life? [...]

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

 
Follow

Get every new post delivered to your Inbox.

%d bloggers like this: