Question

Germline mutation rates tend to increase with the GC (guanine and cytosine) content of a gene. Please support this trend with some examples (ie genes that mutate more frequently in the germline and also have abnormally large amounts of GC content)

Answer 1

Germline mutations are those mutations which take place in the gametes of males and females and thus are transferred from one generation to another. Studies have shown that unlike somatic mutations, the germline mutations are very must associated with the GC content of the gamete chromosomes.

In this regard, studies have shown that the higher is the GC content/region in the gametic chromosomes, the higher are the chances of transcription associated mutation or TAM. This is because the DNase I undergoes hypersensitivity with respect to these regions on the DNA and hence, the rate and extent of TAM increases. For example, the germline mutations for gene foetal growth factor (FGF) shows a higher rate of mutation as compared to other genes due to its particularly high GC content.