Lisa J Edelmann, PhD
, Albert Einstein College of Medicine
, Albert Einstein College of Medicine
, Mount Sinai School of Medicine
The molecular genetics laboratory is focused on the detection of carriers for specific genetic diseases. In particular, the laboratory has been a leading provider of genetic testing for the Ashkenazi Jewish (AJ) community living in the greater New York metropolitan area. This population is at increased risk for a number of autosomal recessive diseases that are lethal in childhood or are associated with significant mental or physical disability. These diseases generally have a limited number of specific mutations and are present in greater than 95 persent of affected patients, due to genetic drift and/or selection. The laboratory also offers pre- and postnatal mutation scanning for Noonan syndrome. In addition, we have recently validated a panel of cytochrome P450 variants for the detection of individuals with genotypes that may require dosage adjustments for specific medications. Research in the laboratory is focused on population screening of Ashkenazi Jewish samples to accurately determine carrier frequencies and allele distributions and assess whether certain mutations or variations may confer increased risk for specific adult-onset diseases.
The molecular cytogenetics laboratory offers Fluorescence in Situ Hybridization (FISH) for a number of chromosome rearrangement disorders, including DiGeorge syndrome, Williams syndrome, Prader Willi and Angelman syndromes, Wolf-Hirschhorn syndrome Cri-du-Chat syndrome, Smith Magenis syndrome and Miller-Dieker syndrome. We are currently developing testing panels using multiplex ligation-dependent probe amplification (MLPA) and targeted array CGH (Comparative Genomic Hybridization) to increase our ability to clinically detect rearrangements that are not visible by standard karyotype analysis but involve genomic copy number changes. Research in the molecular cytogenetics laboratory is focused on chromosome rearrangement disorders and their mechanism of generation. Most chromosome rearrangements occur sporadically in the population at a specific frequency, depending on the disorder. The combined frequency of chromosome rearrangements, balanced and unbalanced, including translocations, deletions, duplications and inversions is estimated at 1 in 300 live births. For many of these disorders, genomic architecture plays an important role in susceptibility to rearrangement. We are currently investigating the mechanism that generates the isodicentric Xq chromosome (idic(Xq)), a spontaneously occurring chromosomal aberration that is present in 18 percent of Turner Syndrome cases, and is the most common constitutional isochromosome in humans. We have collected a number of cell lines to delineate the breakpoints of the idic(Xq) in order to better understand how the architecture in the region of Xp11 influences formation of the isochromosome. Our methods of study include FISH and array CGH, generation of human hamster somatic hybrid cell lines, pulse field gel electrophoresis and long range PCR to amplify across breakpoint junctions. Ultimately, we would like to determine whether specific variations in genomic architecture at the breakpoint regions of recurrent rearrangements confer increased susceptibility to the rearrangement.The laboratory is also involved in a collaborative effort to understand how chromosome rearrangement disorders contribute to autism by investigating the frequency of known micro- deletion and duplication syndromes in autism patients as well as delineating novel de novo rearrangements in autism.
- Long-read HiFi sequencing of NUDT15
- Characterization of Reference Materials for TPMT and NUDT15
- Deletion of ERF and CIC causes abnormal skull morphology and global developmental delay
- Development and Analytical Validation of a 29 Gene Clinical Pharmacogenetic Genotyping Panel
- Haploinsufficiency of the basic helix–loop–helix transcription factor HAND2 causes congenital heart defects
- Lessons learned from expanded reproductive carrier screening in self-reported Ashkenazi, Sephardi, and Mizrahi Jewish patients
- Structural variation at the CYP2C locus
- Prenatal cytogenomic identification and molecular refinement of compound heterozygous STRC deletion breakpoints
- The New York pilot newborn screening program for lysosomal storage diseases
- Integrated CYP2D6 interrogation for multiethnic copy number and tandem allele detection