Monthly Archives: January 2014

New coffee machine?

UntitledWell not quite…….but it will certainly speed up the processing of tissue sections for histology.

Now that we have fully established the lab and successfully transferred our ‘in vivo’ resources to IGM@Newcastle University we are ready to start doing some science again!

Lots of novel genetic models to study and several students joined the lab in the New Year; but more on that later…………….

Cricket and Science

I sense it will be a quite week in skeletal world, so now for something completely different…………….

Can we combine Cricket and Science?

Wouldn’t that be great to do!

4th_Test_Woodfull

The ‘Body line’ series of 1933 and Bill Woodfull ducks a particularly fast and very nasty bouncer from Harold Larwood.

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So, in the spirit of the Semantic Web we will attempt to provide the first framework for their seamless integration……

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Sticky wicket = a difficult experiment to perform (e.g. PCR genotyping for Cre using safeview)

Googly = unexpected & unexplained result

Green top = the data don’t quite match the hypothesis, but work hard on it and who knows…..

Silly mid on/off = those nasty lab jobs that no one likes doing

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Inswinging yorker (a.k.a unplayable) = the very negative comments from reviewer #3

Full toss = your mother is reviewer #1

Decision Review System (DRS) = a direct appeal to the Journal Editor (often on your knees)

Golden duck = the Editor doesn’t even send your paper out for review!

Featherbed wicket = an invited review

Backing up = preparing your manuscript in several different Journal styles (just to be ready)

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Slow low turner = a difficult to read PhD thesis that requires lots of patience and application

Taking guard = every time you go out to lecture to the undergrads

Sledging = THE difficult question, which is always asked by the person who slept through your entire seminar

Geoff Boycott = built from spare body parts of ALL the great scientists

Just how rare is type IX collagen MED?

2577133_gr1

Recently we have re-evaluated MED caused by mutations in the type IX collagen genes (COL9-MED), in part due to our recent revision of the MED GeneReviews Article.

COL9-MED is generally the mildest form of MED and is characterized by joint pain and stiffness presenting in the first decade of life, whilst radiographic abnormalities are primarily restricted to the knees with relative sparing of the hips.

In our most recent 7-year study we concluded that MED resulting from mutations in the type IX collagen genes was the rarest form and accounted for the less than 10% of all genetically confirmed MED.  Most of the mutations were in the gene encoding the alpha2(IX) chain (COL9A2). Indeed, of the 22 known mutations that I am aware of (through publications or our own research) they break down as follows:-

  • COL9A1 = 1 family
  • COL9A2 = 15 families
  • COL9A3 = 6 families

Now that’s not to say that more mutations have not been found by various diagnostic labs around the world, but currently that information is not available.

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What is the geographical distribution of COL9A2-MED?

Although it was proposed in 2006 that COL9-MED was more prevalent in Japan, I just don’t think that the numbers justify this claim. Of the 15 families with confirmed COL9A2-MED; 12 are of Northern European descent and breakdown as follows [UK (4); Netherlands (4); Germany (3); and unspecified (1)]; the remaining 3 are from Korea or Japan.

But, I’m not saying that COL9A2-MED is specific to Europe, because clinical ascertainment and access to genetic testing may be influencing this distribution.

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COL9A2-MED mutations show an interesting distribution across Europe.

The COL9A2 mutations that have been identified to date are all in the splice-donor site of exon 3. Seven different COL9A2-MED mutations have been found in Europe and these are listed as follows (along with their EU distribution):-

  • c.186 G>A     [Germany = 2]
  • c.186 G>C     [Germany = 1]
  • c.186+2 t>c   [Netherlands = 4]
  • c.186+2 t>a   [UK = 1]
  • c.186+4 a>c   [UK = 1]
  • c.186+5 g>c   [UK = 1]
  • c.186+6 t>g   [UK = 1]

The numbers are small so any conclusions have to be taken with a pinch of salt, but it would seem that there is at least one Dutch COL9A2 ‘ancestral’ mutation (c.186+2 t>c), whereas the British families all have different mutations. Two mutations so far account for COL9A2-MED in German families.

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But what now?

Despite our best research efforts we still know the least about MED caused by type IX collagen  mutations. We do know that the COL3 domain of type IX collagen is important because that is where all the mutations are clustered and result in its deletion from the mature protein. The development of relevant model systems is the only way that we will make progress in understanding disease mechanisms.

MED is rare, and COL9-MED is rarer still, particularly if half of the cases in Europe are due to an ancestral mutation. Are we looking at 1 in 100-200,000 people?

Bone Research Society – Rare Bone Diseases Workshop

One for the diary

Bone SocietyBone Research Society – Rare Bone Diseases Workshop

Venue: Rutland Hotel

In association with Arthritis Research UK Rare Bone Disease Topic Specific Group & Findacure

Objectives 

  1. To discuss the relevance of research into rare diseases
  2. To provide an opportunity for participants to hear more about some of the collaborations that have been set up to facilitate research into rare bone diseases
  3. To look at opportunities to collaborate and pool ideas
  4. To provide a networking opportunity

 Please click here for further details. 

There is a £15 charge for participation in this workshop, which includes a buffet supper.

BSR 2014 meeting details here.