We rarely hear of scientific work making positive use of otherwise unhappy situations, perhaps because writers feel they don’t “sell” well. We also don’t often hear about smaller projects. Here a couple’s unfortunate luck with their child is put to good use learning more about brain development.
We all have a brain, in a very real sense two half-brains joined. The two hemispheres of our brains are connected by a sheet of neurons called the corpus callosum.
Some people have two independent, unconnected hemispheres. They have what is known as agenesis of the corpus callosum. Basically, their corpus callosum—the sheet of neurons connecting their two hemispheres—isn’t there.
We’re often told we get half or our genes from each of our parents, and that it’s the mixing up of them makes us unique.
That’s pretty much right, but on top of that we also have some variations of our genes that are not present in either of our parents. They’re called de novo mutations because they arise anew in us: if you were to sequence the genomes of your parents they won’t have them.
Most of the time these de novo mutations don’t do much – but sometimes they do. You can’t “blame” anyone when de novo mutations cause disability or worse, either – it’s sheer dumb luck.
Mutations in some critical genes can have different effects depending on where the mutations are in the gene. Sometimes the same gene turns up in different diseases, with mutations in different places, with different severity in their effects.
Researchers Alexander Bassuk and Elliott Sherr from the University of Iowa Department of Pediatrics got permission to look into the case of an infant with fetal agenesis of the corpus callosum and polymicrogyria. The baby was detected to have lack a corpus callosum at 19 weeks by ultrasound, and confirmed by an MRI scan at 22 weeks. The fetus was delivered at 23 weeks.
The researchers obtained samples, and sequenced all the genes of the parents and the infant. They didn’t sequence the whole genome, just the regions containing genes.
Only one gene was found with a mutation, PRICKLE1.
Biologists often use ‘model’ organisms to learn more about how genes works. They’re not models because they look glamorous, but because they have useful properties for genetics. (Sorry, I know that’s disappointing.)
PRICKLE1 is similar to the gene prickle in the fruit fly, Drosophila, that has long been used in genetics from before the structure of DNA was known. Before you ask, there is also a PRICKLE2 gene.
There are many databases with information gathered about the role of genes, so that what is learnt about a gene in one species can be looked up by those studying it another species. These databases don’t get a lot of attention by the media, but they are very valuable resources for biologists.
This PRICKLE1 codes for a protein, the large molecules that ‘make stuff happen’ in our cells. Looking up the gene function databases, the protein it makes, called prickle homolog 1, is involved in arranging stuff inside our cells (cell polarity). It’s also involved in control the movement of nerve cells in the developing nervous system.
That sounds like a mis-grown corpus callosum, doesn’t it? The nerves making up the corpus callosum haven’t grown across from one hemisphere to the other as they would normally. It might not be right, but it’s a useful clues, a good starting point.
The mutation caused a single amino acid PRICKLE1 to change. Even small changes to critical parts of important proteins can have big effects. (For those that want to know: C.427T>G, S143A.) No other de novo mutations were found, nor were other mutations found in known disease-causing genes.
Thousands of people have had their DNA sequence and large databases of DNA sequences and gene variants have been built up. Comparing the variant they found against these databases, it was new, not observed before. We’re still learning new variants.
We have two copies of each gene, one from each parent. Earlier examples of mutations in PRICKLE1 genes were variants that only showed their effect when both copies of the PRICKLE1 were the mutant variant. In the new case, only one copy (one allele) was mutant.
These more severe mutations can be under-reported because of the foetus dying, and not being examined.
It’s a very small piece of knowledge this one mutation, but that’s how a lot of science rolls. Little bits contributing to a wider picture, that some other scientist will pick up.
Some people with so-called ‘split brains’ go on to live long lives. While these people have disabilities, they can also have unique abilities.
One feature of people lacking a corpus callosum is that they can do things independently with their left and right hands simultaneously, such as the ability to draw a circle with the left and and a square with the right at the same time – try it! I’ve touched on this previously at Code for life in Two Half-brains.
Trivia fans might like that Kim Peek, the inspiration for the character Dustin Hoffman played in the movie Rain Main, was found to have agenesis of the corpus callosum. Unlike the Rain Man, Peek was not autistic. Some have speculated that his absence of a corpus callosum may be a reason for his unusual abilities. Along with a prestigious memory, he could, apparently, read the left page of an open book with his left eye, then the right page with his right eye. Kim Peek’s wikipedia entry makes for interesting reading although it’s worth remembering to treat wikipedia entries as starting points to be confirmed.
A de novo mutation in PRICKLE1 in fetal agenesis of the corpus callosum and polymicrogyria
Alexander G. Bassuk and Elliott H. Sherr
J Neurogenet. 2015 December ; 29(4): 174–177. doi:10.3109/01677063.2015.1088847
1 Some people only have half a brain, but that’s a story for another day.
2 Absence, or more correctly to not make. Genesis is the making of something. A- means the opposite; agenesis is the not making of the thing.
3 The fibres that would make up the corpus callosum don’t run across the two hemispheres of the brain, but instead form bundles within each hemisphere. Some cases have full loss of the connections, other partial.
4 I’m leaving out the sex chromosomes for simplicity.
5 It’s customary in research papers not to give away personal details, and things are often referred to obliquely. I’ve carried how the research paper described it to here.
6 Mutations can also occur in the regions that control genes, so can other ways of changing our genomes (deletions, insertions, duplications and so on), so strictly speaking they can’t rule out that someone in the regions outside the genes themselves also had a role, or were the key change.
7 Proteins are not the only molecules that ‘make things happen’, and some proteins are really architectural things – providing scaffolding or other structural elements.
8 A reasonably reader-friendly one can be found here: https://ghr.nlm.nih.gov/gene/PRICKLE1
A more geeky one, meant for those in research science, can be found here: http://www.genecards.org/cgi-bin/carddisp.pl?gene=PRICKLE1
9 A homolog is something that has come from a common ancestor as what it’s being compared with. The sharp-witted might notice this doesn’t necessarily mean that the two play roles in the same repertoire of biological activities.
Illustration of the corpus callosum from Gray’s Anatomy of the Human Body, 1918. Sourced from Wikipedia, public domain image.