Human Disorders

A

Another God

Registered Member
This is a bit of a technical question, but I was wondering if anyone had any knowledge of why it is (and references would be good too thanks) that human disorders caused by mutation of a single gene are relatively rare and yet disorders caused by mutation in multiple genes relatively common?

Thanks
 
Sickle cell anemia is such a disorder. There are many single gene mutation disorders.
 
An exam question from last years "Recombinant DNA Techniques" subject. ie: the question says "Why are human disorders caused by mutation of a single gene relatively rare and yet disorders caused by mutation in multiple genes relatively common?"

So, if professors of Molecular Biology ask a question like that, I felt safe assuming that it was true, and so thought I might be able to get some ideas on it here.
 
Hum… because multi-gene mutations are usually not hereditary but are mutations in somatic cells through life, cancer is a multi-gene mutation disorder. Also they are more difficult to weed out? I’m guessing on this though.
 
digging into my deep dark memory its because;
a) the same molecular end can be gotten through a wide variety of pathways so quite a few mutations need to occur before symptoms are caused. The cell will also compensate in a holistic fashion and only when it’s overloaded will you get ‘disorders’.
b) mutations tend to effect the quantity or quality a viable enzyme but only a few of these are in such a position that they drastically change the enzyme. (Spelling mistakes occur quite frequently when I type, but only a few affect what the meaning of the lord.)
c) lenny moss proposed (not sure where he got it from) that certain genes play a ‘hub’ function, much like Amsterdam/London/New York airports. A mutation which effects that ‘hub’ will effect a wide number of cellular functions since it is connected within a network of pathways. This may play a role in cancer genes. Disabling mutations in these genes are likely to be lethal to the fetuses.
Sorry can’t cite any of this…actually looking around the web I found’
• Single gene disorders caused by a mistake in a single gene. The mutation may be present on one or both chromosomes of a pair. Sickle cell disease, cystic fibrosis and Tay-Sachs disease are examples of single gene disorders.
• Chromosome disorders caused by an excess or deficiency of the genes. For example, Down syndrome is caused by an extra copy of a chromosome, but no individual gene on the chromosome is abnormal.
• Multifactorial inheritance disorders caused by a combination of small variations in genes, often in concert with environmental factors. Heart disease, most cancers and Alzheimer's disease are examples of these disorders.
In which case the division is between single gene disorders and multifactor inheritance disorders which would need a different answer including the logic that its not surprising that an organism is more effected by its environment in forming ‘disorders’ than by its pre-natal genes.
hope some of that helped
 
Yep, sure did, thanks. Off the top of my own head when I saw the question I thought the answer might have to do with the fact that most genes work in gene-plexes, or at least, each gene funtion may be covered by several similar genes (just thinking of all of the numerous polymerases), so for a disorder to be phenotypically observable, you would need to have multiple gene mutations.

The "Multifactorial inheritance disorders " idea is interesting though. When you think of cancer susceptibility as a result of the failure of many many repair systems etc, then it is necessary that the more mutations you have, the more apparent the 'disorder' would be.
 
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