Biochemistry Questions Biochemistry Questions / Compare and contrast the different approaches used by the IHGSC and Celera to sequence the human genome.

Celera Genomics and the International Human Genome Sequencing Consortium (IHGSC) both used Sanger sequencing technologies in their endeavours to sequence the human genome - this was the most advanced technology at the time. However, there were some differences in the approaches used by the two organisations. The IHGSC, funded by government and research organisations, took a more conservative and proven approach. This involved breaking up the human genome into short sections of approximately 100kb, and cloning these into bacterial artificial chromosomes (BACs). These BACs were then amplified, ordered, and stored in a ‘BAC library’. This allowed for the removal of identical sequences, reducing the overall amount of sequencing required. High-throughput Sanger sequencing technology was then used, with the sequence being assembled in the order of the library. Celera Genomics took a more advanced, riskier approach to their sequencing. Using a shotgun technique, the entire genome was sequenced with many reads being identical or highly similar. Computational analysis was then used to assemble these short reads into a long, consensus sequence. Celera wanted to commercialise the genome, patenting genes, however this was the polar opposite of the IHGSC - they released everything at no charge online. Craig Venter’s (the founder of Celera) genome is available online from Celera’s sequencing endeavours, but it is not used in research due to the restrictions placed on its use by Celera. An issue experienced by both organisations was the large repeat regions in the human genome. Due to the relatively short read lengths employed by Sanger sequencing, of around 800bp, repeat regions many kilobases long are unable to be resolved. This produces a discontinuous sequence, and was the reason only a draft genome was published in 2003. More recently, in 2022, the telomere-to-telomere project completed a final and complete sequence of the human genome, taking advantage of modern advances in sequencing technologies (such as Nanopore and PacBio) to produce longer sequencing reads, improving the resolution of repeat regions. Both of these techniques used by Celera and the IHGSC resulted in massive advances in DNA sequencing technology, and have led to a massive reduction in both the cost and time required today. Today, an entire genome can be sequenced in a desktop device, in just a few days.