Question

say you have deduced that a particular genetic disorder is caused when the body cannot produce a particular enzyme, encoded by gene ABC. Therefore you compare gene ABC’s nucleotide sequence between healthy people and people who have the disorder (because they do not produce the enzyme). But the DNA nucleotide sequence from the start site of transcription to the termination point of transcription is always exactly the same for people in both groups. If this genetic disorder is caused by a mutation in the DNA, where is the mutation likely to be, and how is the mutation acting to result in these observations? Apart from the enzyme itself, what molecule’s absence from the cells of an affected person would verify this?

Answer 1

Now according to the question, the disease is a genetic disease but the gene responsible for the disease doesn't have any mutation. This means that the gene is Completely normal but then how it can result in a disease if it is normal? The answer is simple, there's mutation in other elements which are involved in regulation of genes. These elements can turn on or off the gene to which they belong and their mechanism is different depending upon what they are. Some elements may enhance the transcription while some may repress the transcription. Some DNA elements plays an important role in binding of transcription factors to the gene.

Now since there are multiple answers for this, we can choose what may describe the Gene inability to express without altering other genes.

So to answer the question regarding where the mutation is most likely to be :-

The mutation in this gene is most likely to be in Promoter of the ABC gene. Promoters are found upstreams of the Gene, towards the 5'-end of sense strand and due to the mutation in the Promoter, RNA polymerase is unable to bind to the DNA. Since RNA polymerase can not bind to the promoter of the gene, the gene isn't transcribed and there's no expression of it. This is contributing to the disease formation.

Now the other question is what will be absent from the cells of an affected person :-

Since the Gene isn't getting transcribed, there will be no mRNA in the effected individuals because RNA polymerase make mRNA from DNA. This mRNA then encodes for a protein which result in gene expression. Now since there's no transcription there will be no mRNA and thus, no Protein (enzyme according to the question) either.

So to test this, mRNA quantification should be done.