Monday, 13 May 2013

Genetics of Dupuytren's Disease

Today I am writing a post on the paper entitled 'The Genetics of Dupuytren's disease'. 

This paper is freely available from here (or at least at time of posting it was). A word of warming when I say that this paper is quite technical and I was actually asked specifically go through this (as I have a Molecular Genetics background) and give a summary, if you want more details then please feel free to ask and you can always try to read the paper. This paper is a review so there are many references it cites to get the information so I might not have it all and see the paper for those references for the original data. 

To be honest the only way for me to fully understand a lot of this would be to go through the papers and look at them all and if I can a) get the time b) Get the papers and c) I am interested in the papers (I am more interested in certain aspects of DD) then I might well do that. 

Key words (I am sure most people know a lot of these but thought better to have too many than too few, will try to underline them in the text so you know you can refer back): 

DD - Dupuytren's Disease

Chromosome - The organised structure of DNA that is found in cells.

TGF-B1 - A growth factor that has been linked to DD. Growth factors are proteins that normally 
circulate in the body and help regulate growth, normally increasing growth.

Mitochondria - A part of the cell, they are involved in making energy and are passed down from mother to child. Has its own DNA which is separate from the normal cell chromosomes.

MicroRNA - miRNA is tough to explain without some basic biochemistry / genetic background but basically DNA codes for RNA which codes proteins which then do things. However some DNA codes for small bits of RNA which do NOT get converted to protein and instead have other interactions in the cell that can influence levels of proteins etc so do have an impact on the cell processes. 

The introduction to the paper is the same as always with the usual talk about DD (if you are reading this then you probably know what I am talking about). I did learn that DD is considered to be one of the most common hereditary disorders of connective tissue. 

The paper then goes on to talk about Genetics factors: 

Some of the key points it makes are: 

  • around 40% of patients will have a relative with the condition 
  • genetic transmission is not understood and it is likely to not only be a complex mix of genetic factors but also environmental and lifestyle factors to boot. 
  • There are papers that suggest that chromosomal abnormalities and other cell replication defects are seen in DD derived cells. 
  • The above abnormalities included problems seen with the Y chromosome - although this is work in cells and cells in culture do behave VERY different to cells in humans they are often a good indicator and give the higher chances of DD in men the Y chromosome problems could make sense as it is in men only. 
Genetic Links: 

In part 5 they look at doing an analysis on a single family which have 17DD patients in 5 generation and therefore may be able to identify a genetic link by looking at what they have in common and what they have in common that is different  from control groups. 

It was said that the study in reference 21 has  found a susceptibility region of DNA (same DNA in the family that is not in the control), however this region (labelled DUPC1) has not been published. It suggests that the group involved are probably hiding their results whilst they do further investigation to make sure they get the scoop (yes this is how scientific research works even if sharing the results would help patients quicker). 

Pathways: 

Next they go on to look in different pathways. The first pathway they look at is TGF-B pathway which I have covered several times before. They don'y really add much to the following which I have discussed before: 

Here they have compared the DNA in the mitochondria from 20 DD patients and compared it to a control group, they found that 90% of DD patients had a specific mutation that was not present in the control group. Although this may be significant the problem is coming up  with a hypothesis whereby this mutation would lead to DD. To be honest I can't see how it can but cells can be funny like that and a change that you think would do something does nothing and sometimes a change you think would do nothing has dramatic changes. 

Things noticed from looking in tissue from patients: 

When looking in the genes and their regulation in these tissues there is normally a dysregulation somewhere in the collagen pathway. Whether this is that there is more collagen being produced or if it is there is less being broken down (or something wrong anywhere in those pathways) there is normally something amiss. Again I have covered this sort of things before: 


In this paper they also look at miRNA. In analysis from DD patients they have found there tends to be a similar profile or miRNA in patients which is different in control groups - these markers mainly link to a single pathway. 

More work is going on in all of these areas and it will hopefully lead to new and exciting discoveries that will help DD and LD patients as new drugs that can target the condition are discovered and perhaps genetic profiles are made to determine which treatment might work best.