Computational comparison of two mouse draft genomes and the human golden path

Area of Science:

• Comparative genomics
• Mammalian genomics
• Bioinformatics

Background:

• The advent of mouse and human genome sequences initiated comparative mammalian genomics.
• Two distinct mouse genome assemblies exist: one from the public mouse genome sequencing consortium and another from Celera Genomics, utilizing different methodologies.

Purpose of the Study:

• To critically compare the two latest mouse genome assemblies.
• To demonstrate the utility of combined mouse genomes for human genome annotation.
• To analyze conserved sequence elements (CSEs) for gene discovery and estimation of human protein-coding genes.

Main Methods:

• Comparative analysis of the public mouse genome consortium and Celera Genomics assemblies.
• Comparison of combined mouse genomes against the human 'golden path'.
• Analysis of a conserved sequence element (CSE) database derived from combined assemblies.

Main Results:

• The Celera and public mouse assemblies exhibit approximately 10% divergence.
• Celera assembly offers higher base-pair accuracy and genome coverage; the public assembly provides better sequence quality in specific bacterial artificial chromosome (BAC) regions and is freely accessible.
• Combined assemblies facilitated identification of over 6,000 potential novel genes and provided an estimate of approximately 40,000 human protein-coding genes.

Conclusions:

• Combining both mouse genome assemblies significantly improves human genome annotation, particularly in identifying conserved sequence elements (CSEs).
• A substantial portion of identified CSEs are of unknown function, highlighting potential for new discoveries.
• The creation of a searchable, public CSE database is expected to accelerate discoveries in comparative genomics.