Repetitive DNA sequences exhibit complex structural and energy landscapes, populated by metastable, non-canonical states, that favor expansion and deletion events correlated with disease phenotypes. To probe the origins of such genotype-phenotype linkages, we report the impact of sequence and repeat number on properties of CNG repeat bulge loops. We find the stability of duplexes with a repeat bulge loop is controlled by two opposing effects; a loop junction-dependent destabilization of the underlying double helix, and a self-structure dependent stabilization of the repeat bulge loop. For small bulge loops, destabilization of the underlying double helix overwhelms any favorable contribution from loop self-structure. As bulge loop size increases, the stabilizing loop structure contribution dominates. The role of sequence on repeat loop stability can be understood in terms of its impact on the opposing influences of junction formation and loop structure. The nature of the bulge loop affects the thermodynamics of these two contributions differently, resulting in unique differences in repeat size dependent minima in the overall enthalpy, entropy, and free energy changes. Our results define factors that control repeat bulge loop formation; knowledge required to understand how this helix imperfection is linked to DNA expansion, deletion, and disease phenotypes. Repetitive DNA sequences can adopt a variety of canonical and non-canonical DNA structures resulting in complex structural and energy landscapes with potentially profound biological consequences.
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I love my husband with my whole soul. I learned, growing up, that very principle, that you HAD to marry a member or your marriage was doomed. The important thing is whether or not your spouse will support you in your endevours to live your religion. The misogyny is deep in the Mormon church. I was off travelling the world when I met and fell madly in love with a deployed Marine. I am very active with my work, social life, and activities and independent. I guess I was just hoping there was way for it to work. Should one belief system or lack of one take priority and why. But my relationship with him is worth this small sacrifice. The Holy Ghost will testify that it is true.
I worked my butt off and supported our family through internship, residency and two fellowships always looking forward to the day when he would finally be in practice and things would get 'easier". And her husband now is dead and she is left to wonder about their future. Said he wanted those extra few minutes in the morning, but prefaced it by saying he knew it was selfish of him. A lot of what you say about Support was what I expected to find in residency. He may never come out and say it, but if you mention marriage outside of the church and he's OK with it, you have a slight chance of being happily married to her and not being mormon. Its interesting to read all the doctor wife's comments and experiences. No doubt that all rightetous persons will accept Christ but not everyone that dies will be righteous.