The Emanuel Lab made the initial connection between 22q abnormalities and DiGeorge Syndrome (DGS), subsequently discovering that microdeletions of the region are responsible for the phenotypes of DGS and Velocardiofacial Syndrome. The lab created detailed maps of the 22q deleted region, and elucidated its DNA sequence. In addition, the lab team identified many of the genes on 22q11.2, including TBX1, described the low copy repeats (LCRs) responsible for the deletion, and studied meiotic mechanisms of chromosome 22q11.2 rearrangements leading to the deletions. Currently, the Emanuel Lab uses novel optical mapping technologies to refine the detailed structure of the LCRs.
The lab's continued analysis of constitutional t(11;22) revealed a mechanism for chromosomal rearrangement mediated by the genomic instability of palindromic AT-rich repeats. This led to the discovery of other palindrome-mediated, recurrent, constitutional rearrangements, including the t(8;22), t(17;22) and t(3;8), involved in renal cell carcinoma. The observation that many of these constitutional rearrangements are detected in normal sperm opened a novel line of investigation into meiotic mechanisms of palindrome-mediated rearrangements.
The Emanuel Lab's efforts to identify modifiers of the phenotype of individuals carrying the same genetic lesion are ongoing. Many of the team's studies have focused on uncovering genetic disease mechanisms, such as unmasking a mutation on the remaining allele in the subjects with the deletion or looking for genomic variants that can explain phenotypic differences among patients with the same genetic lesion.
Dr. Emanuel investigates diseases caused by abnormalities of human chromosome 22. These include the most common microdeletion syndrome, 22q11.2 deletion syndrome, and the most common recurrent constitutional translocation in humans, the t(11;22). Her efforts include discerning the mechanisms involved in generating the deletion and translocation as well as looking for modifiers of the phenotype in individuals with the deletion syndrome.