Question

What is your best estimate of the rate of de novo somatic mutations? On what studies do you base your estimate? Explain the method(s) used in those studies and the assumptions on which the numbers are based.

Answer 1

A genetic alteration that is present for the first time in one family member as a result of a variant in somatic cell divison or in a germ cell of one of the parents is called denovo mutations. Denovo mutations in germlines are easy to understand by using sequence analysis and pedigree. The large number of cell divisions required to make a human body inevitably leads to the accumulation of somatic mutations. Such mutations cause individuals to be somatic mosaics. Recent advances in genomic technology now allowed to mesure the rate of somatic diversity and it is expected high levels of somatic mutations within individuals.

Using advanced genomic sequence analysis like NGS experiments (next generation sequencing) the rate of SNV(single nucleotides can be estimated. SNV calling from NGS data are computational methods inoving known population wide SNP (single nucleotide polymorphisms). due to abundancy of avalability of NGS data these techniques becomingpopular for performing SNP genotyping, with wide varities of algorithms designed for specific experimental designs and applications.

Algarithems like VarScan, SomaticSniper, JointSNVMix and Strelka were used to determine the rate of single nucletide varitations in populations using whole genome DNA NGS data analysis from cells.