Genomic Designation

Many thousands of people, most of them children, have had their lives transformed by genetic diagnoses like 22ql 1.2 Deletion Syndrome, Fragile X syndrome and XXX syndrome. None of these conditions can be diagnosed in the clinic based on a patient's presentation: you have one of these ‘genomically designated’ conditions if, and only if, you are found to have a particular genetic mutation. Nevertheless, there are treatment guidelines, specialist clinics, support groups and active foundations dedicated to these and many other genomically designated conditions. Patients and parents are encouraged to view these genomically designated syndromes as their primary diagnosis, with other things ranging from heart defects and clefi palates to autism and intellectual disability recast as symptoms of their underlying genetic disorder. Some of these conditions are very rare, while other straddle the boundary between rare and common disease. Cumulatively, however, genomically designated conditions are not rare at all, and they are playing an increasingly prominent role in the field of childhood developmental difference. They also serve as evidence for programs seeking to transform clinical practice and research towards the vision of “precision medicine”.

When this project began, there was virtually no social science research on these genomically designated syndromes. Furthermore, there was no systematic research on the way genetic mutations are reshaping medical classification more generally. The first paper published using this grant (Navon and Shwed 2012) built on our previous work to show knowledge about genetic mutations can reshape medical classification in complex and powerfirl ways. A second paper introduced this way of thinking to the genetic counseling community and invited them to consider its pitfalls and promises (Navon 2012).

Since then, we have collected a wealth of data and worked on a host of sub-projects dedicated to questions like: how and why does our knowledge about some mutations, but not others, play such a powerful role in the way with think about and manage human difference? How do researchers and advocates create productive points of interface and exchange between genomically designated conditions and the common disorders that they overlap with, like autism? What can these genetically-fixed conditions, with their varied histories, tell us about broader issues in the social studies of science and medicine?

Over the course of the grant period we collected a wealth of qualitative data that was included in two papers that listed BSF as its primary source of funding. The first of these papers (Navon and Eyal 2014) argued that genomically designated syndromes — we focused especially on 22ql3 Deletion/Phelan-McDermid Syndrome (PMS) — thrive as objects of research and social mobilization by virtue of their capacity to interface with, rather than supplant, existing, symptom-based classifications such as autism. We showed that they thus serve to coordinate exchanges of knowledge, biomedical objects and resources between different biosocial communities, despite their ofien incommensurable ends and frameworks of understanding. The second of these papers (Navon & Eyal 2016) leveraged data we collected about changes over time in autism rates in genomically designated syndromes, to demonstrate that the recent rises in autism prevalence and genetic heterogeneity were due to changes in diagnostic practice, rather than to changes in actual causal mechanisms.

Our fieldwork and historical data collection has now been completed. That data will form the core of a book that will be published with the University of Chicago Press as well as several papers that are in the planning stage, all of which will acknowledge BSF as its primary source of funding.

We are the first, however, to admit that we fell well behind our proposed timeline for building a systemic dataset about every genomically designated syndrome. The tasks of identifying genomically designated syndromes, designing and implementing a data collection strategy, working with a team of computer programmers to create a systematic data entry site and then training RAs to complete the data collection all wound up being far more challenging than anticipated. We have made several changes to the original plan in order to meet these challenges; we realized that the only viable approach was to collect data on all of the several hundred singlegene and chromosomal mutations associated with both intellectual disability (ID) and autism. While this was a much larger undertaking than we originally proposed, we plan to use that data to analyze the overall impact of genetics on medical classification and practice in those fields. In other words, rather than just focusing on strong cases of ‘genomic designation’ we will be able to analyze the whole range of outcomes when genetic mutations are associated ID and autism, and we will be able to compare strong with weak cases, as well as with negative cases to tease out causal mechanisms. While the Israeli team participated in the development, QA and beta stages of the data entry system setup and data collection, we ultimately delegated the bulk of data collection to the American team, leaving the Israeli side responsible for communications and administration. In addition, we are collecting a broader range of data about the scientific histories of those mutations as well as the advocacy organizations, research programs and clinical resources dedicated to the syndromes with which that they are associated. For example, we are collecting data on the history of each mutation's association with autism -- a strategy that has already led to publication in one of sociology's two flagship journals (Navon and Eyal 2016). Anticipating the end of the BSF Grant, we have intensified work and data entry recently, and we expect data collection to be completed within the next few weeks.

In the last couple of months, we have completed data collection entries on all the ASD/ID chromosomal mutations and nearly 4/5th of the ASD single gene mutations. We anticipate that we will have collected a single full set for all single-gene and chromosomal mutations by the conclusion of the Columbia University academic year (December 23rd). We have entered and stored about half of these data collection entries for the single-gene and chromosomal mutations onto our data entry website. We have intensified these efforts to ensure that the collected data is all stored onto the data entry site by the end of the year. The data is stored in a relational database. The database holds the mutation entries and information related to those entries, including the scientific histories of those mutations as well as the advocacy organizations, research programs and clinical resources dedicated to the syndromes with which that they are associated.

In short, we are optimistic that our data collection, even if somewhat delayed, will result in a stronger set of research outputs over the next two years on the relationship between genetic testing results, medical classification, clinical practice and patient advocacy movements.