Genomic Diagnostics

Identification of genomic variants related to disease is crucial for diagnostics and clinical care especially in congenital disorders such as neurodevelopmental delay and autistic spectrum disorders. In the Talkowski laboratory, we are leveraging our analytical and statistical methods to generate a more complete picture of individual’s genomic variants and filter out those most likely to be involved in diseases, which can be translated into the clinical setting to aid physician diagnostics. As earlier diagnostics can help better aid in clinical intervention and treatment, we have translated these studies into the prenatal setting. Our research has shown that we can use next-generation sequencing techniques to more fully capture prenatal pathogenic variants than traditional methods such as karyotyping and chromosomal microarrays. We continue to advance this field by investigating safer and more accurate prenatal diagnostics using cutting edge techniques (such as cell-free fetal DNA analysis) that harness the power of our unique genomic analysis. This process will enable physicians to make more accurate diagnostic interpretation in those born with congenital disorders.

Prenatal Diagnostic Sequencing

We are actively developing molecular and computational pipelines for whole-genome sequencing in prenatal diagnostic practice. We previously performed the first clinical diagnosis of a prenatal sample by large-insert whole-genome sequencing, which identified a balanced translocation that disrupted CHD7, resulting in a predicted diagnosis of CHARGE syndrome that was confirmed by clinical features at birth. In another study, we identified chromothripsis by jumping library sequencing in a prenatal sample in collaboration with Dorothy Warburton and Michael Macera of Columbia University. Our laboratory is currently in the process of large-scale validation of whole-genome sequencing in routine prenatal genetic testing for structural variation through an NICHD R01. We are also developing methods to delineate the full mutational spectrum of structural variation from cell free fetal DNA sequencing.


Talkowski et al., 2012, NEJM
Macera et al., 2015, Prenatal Diagnostics