Definition of Complex Rearrangements By Target Capture in Next Generation Sequencing

In this proposal, I will test a new approach: targeted genomic capture followed by new generation sequencing (100 bp paired end reads) of the captured material to rapidly and precisely define the molecular abnormalities in a set of clinically interesting cases followed in the Genetics clinics of the Johns Hopkins McKusick-Nathans Institute of Genetic Medicine (IGM). These include 3 cases with complex dysmorphic syndromes already known to have translocations: the first (family L982181) is segregating an apparently balanced t(2;3)(p15;q12) translocation over 3 generations associated with craniofacial abnormalities; the second (patient JHU2010) has a t(2;6)(q22;p12.3) translocation and a breakpoint in the region of RUNX2 on chromosome 6p, associated with cleidocranial dysplasia (OMIM 119600); and the third (patient L08-2709) has a t(5;17)(q23.2;q24) translocation, with a breakpoint in the region upstream of the SOX9 on chromosome 17q, associated with the clinical phenotype of acampomelic campomelic dysplasia (OMIM 114290).