Physician-scientist Bryn Webb is using Ingenuity Variant Analysis to interpret sequence data from patients with rare congenital facial paralysis disorders. Just a few labs around the world specialize in these disorders, which include Moebius syndrome and other forms of facial palsy. One of these labs is led by Bryn Webb, an instructor in genetics and genomic sciences as well as pediatrics at the Icahn School of Medicine at Mount Sinai and at the Icahn Institute for Genomics and Multiscale Biology. Though she is still early in her career, Webb has already won awards for her genetic research in craniofacial disorders. With Ingenuity Variant Analysis from QIAGEN in her arsenal, she is poised to add even more to the body of knowledge around these disorders.
She is on a mission to make it more straightforward to diagnose people with developmental congenital facial paralysis and associated conditions. Webb is taking a candidate gene approach with next-gen sequencing to elucidate the genetic underpinnings of these disorders. Her gene panel is 2.5 Mb and includes 436 genes she chose based on candidates from animal models in the literature, variants known to be involved in these disorders, and results from her own research that merited additional interrogation. So far, she has sequenced nearly 100 probands, running new samples as they arrive and confirming next-gen results with Sanger.
Webb interprets her sequencing results using Ingenuity Variant Analysis. She uses the platform to exclude the most variable exonic regions and focus on changes that are predicted to be deleterious. “Not only can I sort variants, but then I can also start to look at more complex features,” she says. “I look at whether any variants are common to multiple persons, and then use burden analysis and association features.” She notes that being able to upload sequence results for all 98 probands and analyze variants across them has been especially helpful. “I can see how many variants are common to two people, three people, four people, and so on,” she adds.
Because she used Ingenuity Variant Analysis, Webb also had access to a built-in database of control samples. She used genomic data from the Personal Genome Project and the 1,000 Genomes Project, both available within the QIAGEN platform, to help with the burden analysis interpretation and provide more power than just using dbSNP frequencies. Now she is conducting follow-up studies on the promising variants highlighted in her analysis.
Ultimately, establishing clear genetic markers for these disorders will not only enable physicians to clearly diagnose them — and therefore provide better treatment for patients — but may even contribute to the discovery of prenatal treatments that could detect anomalies and help steer cells toward healthy development.
For more on Bryn Webb’s work on these rare disorders and her use of Ingenuity Variant Analysis, check out the case study here.