Human variation studies at Stanford


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Human variation studies at Stanford

CNV Expert Rajini Haraksingh Studies Human Variation at Stanford, Rare Genomics Institute

Rajini Haraksingh aims for a broad understanding of the complexities of human variation. Along the way, she has uncovered some key genetic causes of disease. She relies on QIAGEN’s Ingenuity Variant Analysis to ask better questions of her data with simplicity and speed.

During the course of her PhD, advances in genome sequencing and variant mapping technologies made it possible to study all of the genetic variants in large numbers of individuals and develop a deeper understanding of normal human genetic variation. Haraksingh gained a strong interest in learning everything she could about the interactions between genes and other DNA elements, and how they work together as a system to produce our phenotypically diverse species.

Now a postdoctoral fellow in Alexander Urban’s lab at Stanford School of Medicine, Haraksingh focuses on the functional implications of copy number variants (CNVs) and other structural variation. This expertise in the fundamental elements of the genome allows her to dive into any disease or condition and make important connections. “I try to understand the interplay between different levels of gene expression and gene regulation,” she says. “How does the entire set of genomic content work together to create a functioning cell, a functioning system, and ultimately a functioning being?”

Her postdoc work, which largely continues her PhD focus, included a study of samples from patients with sensorineural hereditary hearing loss. Earlier work by her colleagues had revealed that taste receptors and olfactory receptors were copy number variable, so Haraksingh theorized that hearing might be another sense affected by CNVs. “It was known that copy number variants were enriched in genes involved in sensory perception and interaction with the environment,” she says.

Using patient samples collected by Stanford pathology professor Iris Schrijver, Haraksingh and her team performed exome sequencing of families and isolated cases, and genome-wide CNV variant mapping on some 300 cases and controls to learn what they could about the complex process of hearing. Both technical approaches were important. Haraksingh says, “One of our most important conclusions was that in order to discover novel contributors to complex disease, we really need to use multiple complementary strategies.”

The project led to a publication in BMC Genomics in which lead author Haraksingh and her collaborators report a novel gene and a novel copy number variant linked to the phenotype. The experimental work yielded thousands of variants that under other circumstances would have required a Herculean effort to interpret using a number of external databases. “It’s extremely challenging to work with these databases. You’re constantly downloading and moving around large data sets,” she says. “It’s really messy and it takes a long time.”

Fortunately for Haraksingh, she was spared the endless hours that such a process would have required. “We came across Ingenuity Variant Analysis and it was a godsend,” she says, noting that the application is connected to those external databases and can easily query them in one fell swoop. “It turned what was an extremely frustrating experience into one that was actually really fun.”

Haraksingh also uses the web application in her nonprofit work with the Rare Genomics Institute, an organization that enables patients to take advantage of genomic solutions for diseases that defy diagnosis. “I’m not an expert in any particular disease,” she says. “I come at this from the angle of trying to understand the variation in the genome, and what that means for developing different diseases.”

To learn more about how Haraksingh used Ingenuity Variant Analysis to discover a novel gene and a novel copy number variation you can download the full case study.

More information

Download full text PDF of this study

Learn more about Ingenuity Variant Analysis


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