Second-Place Abstract Competition Winner

I hope you were able to join us for last week’s webcast where we invited first-place abstract competition winner Michael Iacocca to present on his submission “Using NGS to detect CNVs in familial hypercholesterolemia”.

Today, I’d like to announce our second-place winner, Nicole Weaver, Clinical Geneticist at Cincinnati Children’s Hospital. Nicole adopted VarSeq into her research pipeline in 2015 and has been a valued customer since. Her abstract captured our interest a great discussion on how VarSeq assists her team in sequencing patients with congenital craniofacial and skeletal anomalies, and their plans for continued use in the future.

We will be inviting Nicole to present her abstract with us in a webcast which we will announce at a later date. In the meantime, please enjoy her abstract which I’ve shared below.


Congenital craniofacial and skeletal anomalies affect approximately 1 in 3000 live births. There are hundreds of named craniofacial malformation syndromes including many without a known genetic etiology. Whole-exome sequencing (WES) has rapidly advanced clinicians’ abilities to identify novel genetic etiologies of a variety of phenotypes including craniofacial malformation syndromes. Knowledge of the genetic mechanisms and pathogenesis of craniofacial malformation is necessary for optimizing currently available clinical treatments and for developing new therapies for affected individuals. The goal of our research program is to identify novel genes involved in craniofacial syndromes.

During my residency in pediatrics and medical genetics, I was involved in a divisional rare-disease whole exome sequencing research project. My initial role was as a clinician, submitting patients with a suspected novel disease, but this role expanded to include analyzing the sequencing data and identifying candidate variants. Through this work, I facilitated the discovery of two novel craniofacial malformation syndromes caused by mutations in genes which were previously not known to cause human disease (Weaver, 2015; Gordon, 2015). Although highly confident that I had found the “right” answers for these two cases, functional studies were necessary to prove that in silico predictions were correct and that the variants were indeed pathogenic. I was fortunate to identify external collaborators for both cases, resulting in the identification of additional patients and functional and animal studies that supported pathogenicity. Although my role these cases was extremely rewarding, I became acutely aware that I wanted additional training and experience in bench research so I could design and perform functional studies on animal models. I transitioned to a faculty position with protected time for research and have spent the last 2 years learning basic research techniques instrumental for validating the functional significance of novel variants in poorly understood genes. At the same time, I have been working with colleagues to identify patients with suspected novel craniofacial disorders, and consent these patients and their families for (research) whole exome or whole genome sequencing. The goal of this endeavor is to identify new genes implicated in craniofacial syndromes. Our group was fortunate to receive institutional funding for sequencing, and we recently received raw data from whole-genome sequencing of approximately 20 trios with probands affected by craniofacial malformations. After analyzing the sequencing results for each trio we will choose candidate variants for further study in the lab. Ultimately, we hope to be able to return a genetic diagnosis to the participants.

VarSeq is an essential part of our research pipeline. Every genome (or exome) will be analyzed using VarSeq. The ability to create and modify trio analysis templates and save the templates for use on additional cases is invaluable for ensuring that each trio is analyzed in the same way. Having analyzed exomes prior to VarSeq’s creation, I am particularly aware of the impact this software has on analysis—the user interface is intuitive, and the filtering occurs quickly, leaving more time to focus on learning about the candidate genes identified.  I look forward to continuing to become more familiar with VarSeq’s capabilities as we sequence more patients with craniofacial malformation syndromes.

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