Somatic microindels: analysis in mouse soma and comparison with the human germline.

摘要: Microindels, defined as mutations that result in a colocalized microinsertion and microdeletion with net gain or loss of between 1 50 nucleotides, may be an important contributor to cancer. We report the first comprehensive analysis somatic microindels. Our large database lacI transgene Big Blue® mice contains 0.5% microindels, 2.8% pure microinsertions, 11.5% microdeletions. There appears no age, gender, tissue-type specificity frequency Of independent in-frame insertion deletion, microindels are responsible for 13% protein expansions 6% contractions. These play crucial role oncogenesis evolution via “protein tinkering” (i.e., modest expansion contraction proteins). Four characteristics suggest caused by unique mechanisms, not just simple combinations same mechanisms cause microinsertions First, microdeletions commonly occur at hotspots, but none 30 recurrent. Second, sizes deletions insertions larger more varied than microinsertions. Third, overwhelmingly repeat adjacent base (97%) while do so only infrequently (17%). Fourth, sequence contexts is consistent including recruitment translesion DNA synthesis polymerases. The mouse have similar those human germline causative human, soma germline. Hum Mutat 28(1), 69–80, 2007. Published 2006 Wiley-Liss, Inc.