Lego Sequencing Read Assembly

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What You Do:

Humans have approximately 3 billion base pairs! How can we read this much DNA? One strategy is to break it into pieces, then put them back together. In this activity students can learn how to put multiple sequencing reads back together.

From: Commins, J., Toft, C., Fares, M. A. – “Computational Biology Methods and Their Application to the Comparative Genomics of Endocellular Symbiotic Bacteria of Insects.” Biol. Procedures Online (2009).

What You Need:

LEGO Baseplate

Multiple 2×8 Lego blocks

Index cards (for writing reads)

Scissors (for cutting out reads)

Tape (for taping reads to Legos)


Create a few sentences, and write multiple 2-3 words chunks of those sentences on index cards to cut out and tape to a 2×8 lego block.
Ensure that each 2-3 word chunk has an overlapping word with another.
Each sentence can have redundant reads or missing information, depending on the desired complexity.

Ask students what they know about DNA. All living things have DNA and it provides the instructions for how we’re built.
Explain that our instruction are made up of 3 billion bases, and until recently we didn’t know what they were.
Briefly describe the concept of shotgun sequencing, reading lots of small sections of DNA then piecing it back together.
Tell the students that they will figure out sentences you wrote by putting together different reads.

Break students into groups and give each a sentence to piece together.
When done, have students exchange sentences and try again.
For increased complexity, you can give students mixtures of multiple sentences.

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