With age, somatic cells are thought to accumulate genomic "scars" as a result of the inaccurate repair of double-strand breaks by nonhomologous end-joining (NHEI). Estimates based on the frequency of breaks in primary human fibroblasts suggest that by age 70 each human somatic cell may carry some 2000 NHEl-induced mutations due to inaccurate repair. If these mutations were distributed randomly around the genome, how many genes would you expect to be affected? Would you expect cell function to be compromised?'vVhy or why not? (Assume that 2% of the genome-l.5% coding and 0'5% regulatory-is crucial information.)

The size of the human genome is 3.3 * 10^9 bp, as mentioned the coding and regulatory sequences of DNA is 2 percent of the entire genome, that is, 3.3 * 10^9 bp * 2%, which will be equal to 6.6 * 10^7 bp.

Let us assume that there is equal distribution of the 2000 non-homologous end joining induced mutations. Thus, 1 NHEJ shall takes place after every 3.3 * 10^9 bp / 2000, which will be equal to 1.65 * 10^6 bp in genome.

Now, the number of NHEJ in the regulatory and coding region would be,

6.6 * 10^7 bp / 1.65 * 10^6 bp = 40

A maximum disruption of two genes, that is, one at each end can take place by each NHEJ. Thus, the number of genes getting affected by 40 NHEJ would be 80, that is, about 0.38 percent of the entire genes. About 21000 genes encodes protein in human genome.

Yes, the cell function would be compromised as there will be a loss of gene, and at the same time its products, that is, the regulatory RNAs and protein would drastically influence the activity of the cells.

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