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Asked by agee442pup on 7 Dec 2021.
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Clara Cieza-Borrella answered on 11 Nov 2021:
For me the most complex genes to work are those whose functions haven’t been described. That means that there is not information published about the gene and you don’t know the expected consequences for the cell when you remove or add extra-copies of the gene to a cell….
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Frankie Macrae answered on 11 Nov 2021:
The most complex I’ve come across are large genes that have pseudogenes, this is when there is a very similar sequence somewhere else in the genome (normally very nearby) that doesn’t code for protein (so doesn’t really have a function). This makes it really tricky when we’re doing genetic testing because if we detect a mutation it can be difficult to tell whether it’s in the gene, which could be disease-causing, or in the pseudogene, which wouldn’t be disease causing. We have special ways of confirming mutations that we see in genes that have pseudogenes to avoid this, but the methods can be a bit temperamental.
They can also be a pain when you’re trying to design an assay to look for a specific mutation in a family for example for prenatal testing, as our usual methods work by designing primers that are specific (meaning has a matching sequence) to the exon where the family mutation is, but with pseudogenes it’s very tricky to design something that’s specific as the sequence will also match the pseudogene.
Examples are PKD1 that causes polycystic kidney disease, SMN1 which causes spinal muscular atrophy and STRC which causes deafness.
tl;dr Pseudogenes are annoying!
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Becky Cohen answered on 11 Nov 2021:
Some genes have ‘pseudogenes’ that are almost identical in sequence but that are non-functional. It can be really challenging to analyse these genes without getting them confused with each other. I’m working on a project at the minute trying to figure out a way to improve this.
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Thomas Nicol answered on 11 Nov 2021:
The most challenging I have come across is a gene called Titin. It is involved in the function of all of our muscles and is the largest known gene. It has over 350 exons making it incredibly long and difficult to work with for many assays.
However, like other people have said, there are also many smaller genes that are difficult to work with for a variety of other reasons and sometimes you can’t know a gene is going to be particularly troublesome until you start working with it.
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Jeffrey O'Callaghan answered on 11 Nov 2021:
Probably really long genes like the one that causes muscular dystrophy. These long genes can have repeating DNA codes, be processed by proteins into different versions of the same gene, or contain a lot of junk (introns) and sometimes we don’t know what it does. All of these together make it very hard to isolate, replicate and study in the lab!
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Dapeng Wang answered on 11 Nov 2021:
For me, the most complex gene is the longest gene. Typically, a gene is composed of exons and introns. For some genes, they have super large introns, leading to the super large genes. It is difficult to understand how this kind of genes work in terms of transcription and translation.
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Joaquin de Navascues answered on 11 Nov 2021:
Some genes are very difficult to work with because they can produce many different proteins, and it is extremely difficult to know which one has an effect. An example of this is the DSCAM gene in the fly Drosophila melanogaster, which can produce more than 38,000 protein variants (the whole Drosophila genome has ~15,000, and the human genome is about 25,000)
Other genes are very difficult because it is repeated many times in the genome, like the genes for Histones (proteins that pack DNA in the nucleus). If you want to modify these genes in your experimental system, you need to change them all, or there will be some copies left normal, which will continue working as usual and you will not be able to observe an effect in the cell that allows you to guess their function.
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