We’re posting a series of blog posts explaining genetics for the layperson in the context of their health.

This is part two of the series, and describes how de novo genome sequencing is done. Other posts in this series:

  1. Part 1, genotypes, phenotypes, and polymorphism

This video describes how DNA is extracted from a biological tissue sample and prepared to form a “library” of bacterial clones that contain small pieces of the sample’s DNA. These bacteria are then grown in culture and sequenced using the Sanger method:

After the DNA is read out, it needs to be assembled. This traditional method of sequencing and assembly focuses on reading out longer sequences, which can be assembled with fewer readouts of each position:

Contrast traditional sequencing with shotgun sequencing and assembly, shown here:

The main consideration when choosing between traditional and shotgun methods of sequencing are, roughly:

  • Price per base sequenced (physical materials)
  • Price per base assembled (computing costs)
  • Shotgun method produces sequence at a higher rate, but with more errors and has more assembly problems

Lower costs for sequencing each base favor the shotgun method over the traditional method. Shotgun sequencing is the method of choice today because of decreases in price-per-base sequenced, to be discussed in a later article.