title: Trials and Tribulations with VH Replacement.
abstract: VH replacement (VHR) is a type of antibody gene rearrangement in which an upstream heavy chain variable gene segment (VH) invades a pre-existing rearrangement (VDJ). In this Hypothesis and Theory article, we begin by reviewing the mechanism of VHR, its developmental timing and its potential biological consequences. Then we explore the hypothesis that specific sequence motifs called footprints reflect VHR versus other processes. We provide a compilation of footprint sequences from different regions of the antibody heavy chain, and include data from the literature and from a high throughput sequencing experiment to evaluate the significance of footprint sequences. We conclude by discussing the difficulties of attributing footprints to VHR.
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA.
authors: Wenzhao
authors: W
authors: Meng
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA.
authors: Sahana
authors: S
authors: Jayaraman
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, PA , USA.
authors: Bochao
authors: B
authors: Zhang
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, PA , USA.
authors: Gregory W
authors: GW
authors: Schwartz
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA ; Center for Personalized Diagnostics, University of Pennsylvania Health System , Philadelphia, PA , USA.
authors: Robert D
authors: RD
authors: Daber
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, PA , USA ; Department of Microbiology and Immunology, College of Medicine, Drexel University , Philadelphia, PA , USA.
authors: Uri
authors: U
authors: Hershberg
authors: Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA.
authors: Alfred L
authors: AL
authors: Garfall
authors: Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, WA , USA.
authors: Christopher S
authors: CS
authors: Carlson
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA.
authors: Eline T
authors: ET
authors: Luning Prak
keywords: DH; V(D)J recombination; VH; VH replacement; and JH gene segments; receptor editing