Over the years, scientists around the world have been using our bioinformatics solutions in their research. We feel privileged that our applications have been assisting scientists in uncovering greater insights, landmark discoveries, and helping further the research that has a direct impact on humanity.
We are starting a new blog series to showcase some of these research papers from QIAGEN Bioinformatics customers. Today, we recap a handful of recent publications that used Ingenuity® Variant Analysis™ to help make sense of complex or hereditary disease phenotypes.
The use of whole-exome sequencing to disentangle complex phenotypes
First author: Hywel J Williams
This paper in the European Journal of Human Genetics comes from University College London’s GOSgene group, including lead author Hywel Williams, one of our featured researchers. Published in June, “The use of whole-exome sequencing to disentangle complex phenotypes” reports the identification of a causative mutation in two children with a previously uncharacterized disease marked by abnormal bronchial widening and peripheral neuropathy. The team used Ingenuity Variant Analysis to study exome sequence data, extracting the variants most likely to be causative. For more information on this paper, click here.
Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry (PLoS One)
First author: Louis Viollet
In May, a large team of scientists from institutions around the world report an ambitious effort to stratify patients with AHC, a neurological disorder associated with repeated bouts of temporary paralysis. The researchers analyzed mutations and genotype-phenotype correlations in nearly 200 patients, then used Ingenuity Variant Analysis to evaluate mutations detected in sequence data. In addition to finding novel mutations associated with the disorder, the team also determined that one known variant was linked to earlier onset and more severe symptoms, potentially offering a more accurate prognostic indicator (biomarker?) for newly diagnosed patients. You can read more about this work here.
A nonsense mutation of human XRCC4 is associated with adult‐onset progressive encephalocardiomyopathy
First author: Leonardo Bee
In the April issue of EMBO Molecular Medicine, scientists from Italy, the UK, and the US used exome sequencing to study twins with a progressive neurological syndrome; symptoms included cognitive impairment and depression, and both twins also had dilating cardiomyopathy. The publication reports the discovery of a homozygous nucleotide change affecting a protein associated with DNA repair. Ingenuity Variant Analysis was used to zero in on variants in the XRCC4 gene known to be involved in DNA repair. Using Ingenuity Variant Analysis’ Path to Phenotype™ investigators were able to link impairment of the XRCC4 gene to the subject’s observed developmental disorders. To learn more, click here.
Exome sequencing of case-unaffected-parents trios reveals recessive and de novo genetic variants in sporadic ALS
First author: Karyn Meltz Steinberg
In March, scientists from Washington University in St. Louis and the University of Sydney published this paper in Nature Scientific Reports. In it, they describe exome sequencing of 44 trios of patients with ALS and their unaffected parents. Using Ingenuity Variant Analysis as well as other analysis tools, they found a number of homozygous recessive and de novo variants that may be implicated in the disease. “This trio study indicates that rare private recessive variants could be a mechanism underlying some case of sporadic ALS, and that de novo mutations are also likely to play a part in the disease,” the authors report. Learn more about this work here.
Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients
First Author: Bai-Wei Gu
Finally, this May PLoS One publication from researchers at the Children’s Hospital of Philadelphia reports the use of induced pluripotent stem cells from patients with dyskeratosis congenita, a rare syndrome affecting bone marrow. By comparing these cell lines to ones with knocked-in wild type genes correcting the dysfunction, the scientists could analyze changes in telomere activity associated with the syndrome. The team used both Ingenuity Variant Analysis and Ingenuity Pathway Analysis (IPA) to look at mutations and gene expression data, finding decreased WNT signaling in mutant cells. Research paper is available here.
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