Mutation mapping and identification by whole genome sequencing
Leshchiner, I., Alexa, K., Kelsey, P., Adzhubei, I., Austin, C., Cooney, J., Anderson, H., King, M., Stottman, R., Ha, S., Drummond, I., Paw, B.H., North, T., Beier, D., Goessling, W., and Sunyaev, S.
Leshchiner, I., Alexa, K., Kelsey, P., Adzhubei, I., Austin, C., Cooney, J., Anderson, H., King, M., Stottman, R., Ha, S., Drummond, I., Paw, B.H., North, T., Beier, D., Goessling, W., and Sunyaev, S. (2012) Mutation mapping and identification by whole genome sequencing. Genome research. 22(8):1541-1548.
ABSTRACT
Genetic mapping of mutations in model systems has facilitated the identification of genes contributing to fundamental biological
processes, including human diseases. However, this approach has historically required the prior characterization of informative
markers. Here, we report a fast and cost-effective method for genetic mapping using Next Generation Sequencing that combines
single nucleotide polymorphism discovery, mutation localization, and potential identification of causal sequence variants.
In contrast to prior approaches, we have developed a Hidden Markov Model to narrowly define the mutation area by inferring
recombination breakpoints of chromosomes in the mutant pool. In addition, we created an interactive online software resource
to facilitate automated analysis of sequencing data and demonstrate its utility in the zebrafish and mouse models. Our novel
methodology and online tools will make Next Generation Sequencing an easily applicable resource for mutation mapping in all
model systems.
