Genetics

This week is PWSA UK Awareness Week. The Prader-Willi Syndrome Association UK want to spread the word about the rare chromosome disorder. They want more people to know about the syndrome, in an effort to allow children and adults with PWS to be understood and accepted, and to make more people across the country aware of what the condition means for PWS people and their families, friends, and carers.

Genetics

Genetics is complicated. There is no medical explanation, for example, for the existence of Katie Hopkins. We do, however, know a bit about the genetic causes of Prader-Willi Syndrome.

I am now, foolishly, going to try to explain it. I’m taking a big breath, and diving in. Any scientists reading, feel free to pull me out when I start to panic...

Most of our body’s cells contain 46 chromosomes (23 from our mother and 23 from our father). These tiny structures are packages of genes which contain the instructions our bodies need to grow, develop and function properly. (The ‘saying no to a glass of wine’, ‘ever wanting to vote Tory’  and ‘dancing without looking like a numpty’, packages in my DNA are missing, obviously).

Egg and sperm cells normally contain just 23 chromosomes, so that they join up in conception to provide the baby with the 46 needed. The joining up bit is where changes or errors in genes and chromosomes can occur. I am a big fan of the joining up; not so keen on the errors.

Many genetic disorders are caused by a change in a single gene and can be passed down from parent to child. But Prader-Willi, apart from some exceptional cases (see below), is not an inherited condition; it just happens. More than one gene is involved, but they are all near to eachother in an area of one particular chromosome: chromosome 15. Every case of PWS is due to the baby not receiving active genes from this particular area of the father’s copy of chromosome 15. The mother’s genes in this area on her copy are ‘turned off’ because of a rare process called ‘genomic imprinting’. (Anyone else think this sounds like a phrase for a typo on a Snow White And The Seven Dwarves poster? Oh, just me then).

There are at least three different chromosome errors that can keep the key PWS group of genes from working normally: 

1) Paternal deletion
About 70% of all cases of PWS are where - with no known explanation - the critical PWS section of chromosome 15 (or The Bastard Bit Of The Bastarding Bastard, as I like to call it) is missing. The section has disappeared, and there’s no rhyme or reason to it. (Although a rhyme would be pretty rubbish: ‘It’s a paternal deletion, our blinds are Venetian’. See?). The deletion is inexplicable, and there is a less than 1% chance of it happening in another pregnancy. This is the genetic reason for my daughter’s PWS.

2) Maternal Uniparental Disomy (UPD).
Yes, this sounds like a Peel Session. “A great live track from Maternal Uniparental Disomy there - three more from them later...”. UPD is a less common form of PWS (about 25% of cases are caused by it), and it is where the baby inherits both copies of chromosome Bastarding Bastard from the mother. Even though there are two complete copies of the chromosome, the key genes are imprinted - ‘turned off’ - resulting in PWS. This has the same effect as a deletion. Again, there is very little chance of this happening again in a further pregnancy (in fact, it never has).

3) Imprinting Defect 
In very rare cases (less than 5%), the PWS genes on the father’s chromosome are there, but do not work because his imprinting process is faulty. Chromosome 15 has a tiny little control centre (imagine the bridge of the Starship Enterprise), which is responsible for ‘switching on’ all its genes. When there is a tiny defect in the imprinting control centre, the PWS section may not be switched on correctly. (Imagine if Captain Kirk accidentally knocked out a power lead when having sex with a green alien woman while his shipmates were in the canteen. That sort of thing). An imprinting defect can appear suddenly, or can be present in the father’s chromosome he received from his mother. If the latter is the case, then there is a 50-50 chance that any child he has will receive the defective chromosome, because, crucially, the defect has now crossed to the father’s side. Further testing and genetic counselling are hugely important for families with a child whose PWS is caused in this way.

So, I hope I’ve made that all clear. References to Snow White and Star Trek may or may not have helped. I don’t think a quick burst of Heigh Ho! or a panic about the reoccuring shortage of dilithium crystals has anything to do with Prader-Willi. Although an urge to be beamed to another planet does occasionally cross my mind. 

Please note: most* (*all) of the facts on this page have been heavily influenced* (*stolen) from the Genetics Of Prader-Willi Syndrome section of the Prader-Willi Syndrome Association USA's website. To read the original, more detailed, and much more sensible article, click here.

Video is Mull Historical Society - Minister For Genetics And Insurance MP

Polling

You’ve heard of Gallup Polls? Well, my daughter is slowly perfecting her own similar method of gathering data. Mind you, with her day-dreamy, meandering walk, it’s not so much a Gallup as a Lollop.

We’ve been attending a few PWS events lately, organised by parents, volunteers, or staff from the Prader-Willi Syndrome Association UK. And my girl’s Lollop Polls are stepping up a gear.

The questions at today’s sunny, sociable PWS picnic at Coram's Fields in Central London, weren’t just the usual “What’s your name?”, “Have you got Prader-Willi?”, “How old are you?” and the slightly random “How many teeth do you have?”. Oh no, a new, astonishingly scientifically accurate, belter of a question has been added to the repertoire...

[Before I repeat it for you, I should check if you’re familiar with the genetic doobriewotsits of PWS. Wrap your noggin around this explanation:

Three PWS girls, and Trevor (Professional Photobomber)

PWS is caused by a baby not receiving active paternal genes from a specific part of one chromosome (chromosome 15). Around 70% of all cases of PWS are caused by a deletion, which means a tiny part of chromosome 15 inherited from the father is missing. Around 25% of cases are caused by maternal uniparental disomy (UPD), which means that instead of taking one copy of chromosome 15 from their dad and one from their mum, the child has ended up with two maternal copies. The remaining 5% of cases are caused by an imprinting defect.

OK? So far, so clear? I’ll let you into a little secret, I wasn’t aware of the third cause, the imprinting defect one. (It sounds a bit like the daily battle I have with my Canon inkjet, to be honest). Consequently, my daughter hasn’t heard of this either, so it didn’t figure in today’s super duper question. If it’s OK with you, let’s not mention it to her. I’d feel a bit like the confused cardinal from the Spanish Inquisition: “The chief cause is deletion...and UPD...the TWO causes are deletion and UPD....and imprinting defect...the THREE causes are deletion, UPD, and imprinting defect....AMONGST the causes are...I’ll come in again shall I?” ]

Her question to PWS children today (or to their parents to answer on their behalf) was this: “Have you got the Prader-Willi where it’s a little bit missing from the chromosome like me, or have you got the rarer one where its a double one from your mummy?”

That’s a cracking query, isn’t it? (The results of the poll were pretty much in line with the statistics mentioned above, by the way). She’s been quizzing her dad about PWS and its causes lately, and to be fair to him, he sounds like he came up with a simplified summary that the bird from Nina And The Neurons would be proud of. Thinking about it, he does take a rather special ‘one for the dads’-type interest in Nina. Mr Drake, if you’re reading this, no, it would not be an anniversary treat if you buy me a lab coat, tell me to put on a Scottish accent, and inform me of a perplexing problem that can only be fixed by me using my sense of touch.* (*I realise this makes little or no sense to non CBeebies viewers, because you have a life).

Where was I? Oh yes, the picnic. So I was proud of my daughter today. Coping with train delays. Asking her questions. Shyly answering other people’s questions. Holding a lovely PWS baby boy, who we kidnapped and held cuddle hostage until he had to be prised from our arms (see photo, top right). 

And the good news is, we’ve got not one but two more PWS get-togethers this month: a picnic in a park in Manchester, which is nicely timed to coincide with a visit to relatives oop north, and a party in a Mormon church hall in Enfield where in order not to offend the Salt Lake City brethren we can’t drink tea or coffee because they think caffeine is the seed of the devil, or sumfink like that. I am, of course, planning to mainline Red Bull before I go.

Song is Black Heat - Questions And Conclusions

Click here for full details of the PWS family events in June

Century

15/11/13 is a Significant Date.

Bear with me, and I’ll explain. Prader-Willi Syndrome is caused by a spontaneous alteration on chromosome 15. A little missing stripe. If you want to get all technical about it, geneticists label this region 15q11-q13. There are also two other chromosome disorders which have the same genetic alteration (Angelman's Syndrome and Dup15q) and which share some, but not all of the characteristics of Prader-Willi.*

Because this 15q11-q13 number resembles the date 15/11/13, which of course only rolls around once a century, the International Prader-Willi Syndrome Organisation and other people and groups involved with PWS used it to try to further awareness of the syndrome. Fundraising events were organised; blog posts posted; T-shirts printed; conversations started.

Today, of course, is the 16th. So I managed to mark the significant date of 15/11/13, which, if you recall, only comes around every 100 years, by remembering it 24 hours too late. I blame my poor organisational skills, which don’t have anything to do with any missing stripes on particular chromosomes, and are entirely due to me being a numpty.

See you back here next century then? Stick it in your diary - but good luck with scrolling through your smartphone’s calender to get to 3013...

*Click here to go to the IPWSO website page featuring a very clear diagram explaining the connections between the three 'chromosome 15 deletion' disorders.

Song is Blur - End Of A Century