Robert S Wood, Jacqueline Krumrey
Examining differences in trends in the orthopedic surgery match for osteopathic and allopathic medical graduates after the transition to single accreditation
Journal of osteopathic medicine
detection structural variants svs currently biased toward alter copy number relative contribution inversions toward genetic disease unclear study analyzed genome sequencing data 33924 families rare disease 100000 genomes project database hosting 500 million svs focused 351 genes haploinsufficiency confirmed disease mechanism identified 47 ultrarare rearrangements included inversion 24 bp 364 mb 2047 de novo validation utilized number orthogonal approaches including retrospective exome analysis rnaseq data supported respective diagnoses six participants phenotypic blending apparent four probands diagnostic odysseys common theme 50 years one individual targeted analysis specific gene already performed 30 individuals findings provide formal confirmation european founder origin intragenic msh2 inversion two individuals complex svs involving mecp2 mutational hotspot ambiguous sv structures resolved using longread sequencing influencing clinical interpretation de novo inversion hoxd1113 uncovered family kantaputratype mesomelic dysplasia lastly complex translocation disrupting apc involving nine rearranged segments confirmed clinical diagnosis three family members resolved conundrum sibling single polyp overall inversions play small notable role rare disease likely explaining etiology around 1750 families across heterogeneous clinical cohorts