Principal Investigator, "Unified Clinical Genomics Database" (U41 Grant)
Awareness and identification of autism spectrum disorders (ASDs) have accelerated at blazing speed. The number of children identified as being on the autism spectrum has increased tenfold in the past 40 years. The pace of technology used in identifying autism spectrum disorders has also been increasing at a rapid rate, and the career of Martin has been swept along with the improving technology.
Martin’s postdoctoral training at the University of Chicago began by using Giemsa banding or G-banding to look at structural rearrangements in chromosomes. G-banding is a technique used in cytogenetics to produce a visible karyotype by staining condensed chromosomes. When Martin compared the use of G-banding to DNA–based probes that she helped develop she found that a significant percentage of the chromosomes had deletions and duplications that were not detectable by routine G-banding. The advent of DNA-based microarray technology allowed researchers to look along the length of every chromosome at a resolution they could never do with older techniques. As Martin says, “This rapid evolution was where my interest in technology development began, and we wanted to discover better ways to identify these deletions and duplications from a research and clinical perspective.”
This new technology allows researchers such as Martin to identify many new syndromes, especially for children with intellectual disabilities or ASDs. Martin is partnering with the Simons Foundation, the largest private foundation that supports autism research on several projects, one of which is examining a copy number variation (CNV) that can cause autism—16p11.2—to better define the genotype and phenotype characteristics. During this project, children with that CNV are examined from a behavioral, psychological, and brain imaging standpoint. It is this genetics-first approach that attracted Martin to Geisinger and specifically to ADMI. The goal of ADMI is to build a clinical research entity where the patients are approached from a perspective of defining the etiology first. For example, children with deletions of the 22q telomere region can experience very severe speech delays, while children with a 16p deletion have more problems with obesity. If the genetic cause of ASD is known in advance, the clinician can tailor treatment plans more individually for the child.
Another area of research interest for Martin is the development of a clinical genomics database. This project stems from her work (in conjunction with David Ledbetter, PhD, Geisinger’s Chief Scientific Officer) with the International Standards for Cytogenomic Arrays (ISCA) Consortium. They launched a pilot project to create a database for clinical and research purposes that collects CNV data in a de-identified way, but that encourages uniformity in terms of interpreting results across different clinical laboratories. This database is particularly significant for researchers and clinicians working with patients who have rare CNVs. These single cases often don’t make it into the literature, so this database allows clinicians and researchers to share data they might not otherwise have known about. NIH has developed a new database, ClinVar, based on this original database. As Martin describes it, “Our ultimate goal is to improve data sharing among laboratories and clinicians to guide clinical interpretation of genomic variation–something that is becoming a part of medical practice every day.” The database will allow for shared knowledge, standardization and ultimately improved quality of patient care.