Prader-Willi syndrome is a genetic disorder that, in infancy, causes poor feeding and low muscle tone, and then in childhood, causes overeating, intellectual disability, and low sex hormones starting in childhood.
Prader-Willi syndrome happens when a handful of genes on chromosome 15 aren’t transcribed into messenger RNA and therefore aren’t expressed.
Among these are SNRPN which stands for Small Nuclear Ribonucleoprotein Polypeptide N and a cluster of snoRNAs, which stands for small nucleolar RNAs, and these genes all have protein products that modify other RNAs.
Now, normally, the copies of the genes contributed by the mother, or maternally derived genes, to this region, are silenced, or turned off, and only the genes from dad, or paternally-derived genes, get expressed.
This special genetic process is called imprinting, where only one copy of the gene gets expressed, not both.
And this differs from most genes in the genome, where both the maternal and paternal copies are expressed.
So those maternal copies in this region are imprinted and therefore silenced.
And this silencing of the maternal copies is an epigenetic process.
In the word “epigenetic”, “epi” means outside of, and “genetic” refers to the DNA sequences of A’s, C’s, G’s, and T’s.
So epigenetic silencing of a gene means turning it off while keeping the DNA sequence itself the same.
The Prader-Willi genes get turned off when methyl groups get attached to the DNA, a process that happens way back when the mother was making an egg.
Even after fertilization of the egg and all of the cell divisions it takes to make a person, that epigenetic mark remains, kind of like a reminder to keep those maternally-derived copies of the genes turned off.
Unfortunately, though, this means that if paternal copies of the genes don’t get expressed, then there aren’t any backup copies being expressed, and so no copies get expressed!
And this is what happens in Prader-Willi syndrome!
Now, there are a few ways these paternal genes wouldn’t be expressed.
The most common one is a deletion on the paternal genes spanning Prader-Willi region.
A lot of deletions also include a nearby gene called OCA2, which codes for a pigment that gives color to the eyes, the hair, and the skin.
