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ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Animal Health Genomics » Research » Publications at this Location » Publication #360201

Research Project: Genomic Intervention Strategies to Prevent and/or Treat Respiratory Diseases of Ruminants

Location: Animal Health Genomics

Title: A computational method to quantify the effects of slipped strand mispairing on bacterial tetranucleotide repeats

item Harhay, Gregory
item Harhay, Dayna
item Bono, James - Jim
item CAPIK, SARAH - Texas A&M Agrilife
item DEDONDER, KEITH - Veterinary And Biomedical Research Center, Inc
item APLEY, MICHAEL - Kansas State University
item LUBBERS, BRIAN - Kansas State University
item WHITE, BRADLEY - Kansas State University
item LARSON, ROBERT - Kansas State University
item Smith, Timothy - Tim

Submitted to: Nature Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/6/2019
Publication Date: 12/2/2019
Citation: Harhay, G.P., Harhay, D.M., Bono, J.L., Capik, S.F., DeDonder, K.D., Apley, M.D., Lubbers, B.V., White, B.J., Larson, R.L., Smith, T.P.L. 2019. A computational method to quantify the effects of slipped strand mispairing on bacterial tetranucleotide repeats. Nature Scientific Reports. 9:18087.

Interpretive Summary: Bacterial infections in animals and humans cause diseases that can lead to death. The cost of treatments and other loses in the cattle industry has been estimated to exceed US$1 billion/year in North America alone. If the effects of bacterial infections in other animal species and humans are included, the economic and social impact is staggering. We have found a new way to monitor changes in bacterial DNA in processes that bacteria employ to evade the host immune system, infect the host, and to increase the severity of the disease. This new way of measuring changes in bacterial DNA can be applied to different bacterial species causing disease in agriculturally important animals and humans. This new level of detail about changes in bacterial DNA will lead to new treatment targets and procedures with the goal of reducing or eliminating the effects of bacterial infections.

Technical Abstract: The virulence and pathogenicity of bacterial pathogens are related to their adaptability to changing environments. One process enabling adaptation is based on minor changes in genome sequence, as small as a few base pairs, within segments of genome called simple sequence repeats (SSRs) that consist of multiple copies of a short sequence (from one to several nucleotides), repeated in series. SSRs are found in eukaryotes as well as prokaryotes, and length variation in them occurs at frequencies up to a million-fold higher than bacterial point mutations through the process of slipped strand mispairing (SSM) by DNA polymerase during replication. The characterization of SSR length by standard sequencing methods is complicated by the appearance of length variation introduced during the sequencing process that obscures the lower abundance repeat number variants in a population. Here we report a computational approach to correct for sequencing process-induced artifacts, validated for tetranucleotide repeats by use of synthetic constructs of fixed, known length. We apply this method to a laboratory culture of Histophilus somni, prepared from a single colony, and demonstrate that the culture consists of populations of distinct sequence phase and length variants at individual tetranucleotide SSR loci.