Knome Awards Human Exome Sequencing and Analysis to Biomedical Researchers

Knome, Inc. Has announced the winners of its inaugural KnomeDISCOVERY Awards, a program designed to spur new genetic insights into health. Researchers Judith Conroy (University College Dublin, Ireland), Eitan Friedman (Sheba Medical Center, Israel), and Abhimanyu Garg (University of Texas-Southwestern Medical Center, USA) have been awarded KnomeDISCOVERY™ exome sequencing and comparative analysis packages.  Each winner will use Knome's integrated sequencing and analysis service to compare the protein-coding genes of two strategically chosen people in order to answer an important question about human health and physiology.
"We received entries from researchers all over the world, reflecting a global groundswell of interest in exome-based research," said George Church, co-founder of Knome and chair of the KnomeDISCOVERY Awards selection committee. "The proposals targeted a variety of creative and compelling research questions.  Our winners represent three outstanding applications of comparative exome analysis. Each will leverage Knome's research-supportive service to identify key similarities and differences between two people's complete sets of genes, spotlighting distinctive DNA spellings that help explain why some people develop a disease or other important phenotype."
Casting new light on aging and fat metabolism
Abhimanyu Garg, MD, is Chief of the Division of Nutrition and Metabolic Diseases at UT Southwestern Medical Center, and a leading expert on neonatal progeroid syndrome (NPS), a debilitating disease in which children appear to age quickly and cannot store enough fat to stay healthy.  In his research, Dr. Garg has documented several subtypes of NP, and hopes to trace their causes to specific genetic variants.
"Exome analysis is a boon to clinical researchers like me, letting us look at all protein-coding genes in one go so that we can better understand puzzling diseases like NPS," Dr. Garg noted, adding that, "Knome will help me quickly accomplish what before would have taken years of costly effort."
Using KnomeDISCOVERY™, Dr. Garg will thoroughly survey two patients' genes, in order to identify distinctive or shared DNA spellings that cause NP.  Ultimately, his findings may help physicians treat NP more effectively and may also cast new light on questions of broad public interest: how we age, and how our bodies process fat.
"Though rare, Progeria holds clues to health concerns that are important not just for people with the disease, but for many others as well – including people suffering from cardiovascular disease. Exome analysis can help find the genes that influence disease severity in Progeria," said Leslie Gordon, MD, PhD, medical director of The Progeria Research Foundation. "Such understanding may allow earlier disease detection, and help prevent or ease debilitating symptoms."
Breast cancer in families: beyond the usual suspects
Breast cancer kills more women than any cancer except lung cancer.  Public understanding of breast cancer risk has grown, thanks largely to discoveries that women who carry certain DNA spelling variants in the BRCA1 and BRCA2 genes tend to get the disease.  These genes, however, account for only a small percentage of all breast cancer cases – most cases remain unexplained.  
In his work at Sheba Medical Center, Eitan Friedman, MD, PhD studies families with heritable forms of breast cancer who carry 'normal' versions of BRCA1, BRCA2 and other well known culprit genes. Using Knome's exome sequencing and comparative analysis, Dr. Friedman aims to find the genetic basis of cancer susceptibility in two such families.  He will then be able to validate whether newly identified cancer-implicated variants turn up in other cancer-prone families too.  In doing so, he stands to refine our understanding of how breast tumors form and spread and to point the way toward better personalized treatment strategies.
"Genome sequencing and analysis are quickly becoming essential tools in efforts to understand, treat, and cure cancers," noted Dr. Friedman. "Well-integrated analysis services like Knome's can help researchers immensely by quickly drilling down to candidate variants that can catalyze vital insights."
Linking a rare disease to an enduringly familiar mystery
In the clinical genetics work at University College Dublin, post-doctoral fellow Judith Conroy, PhD, encountered two Irish families who share a remarkable circumstance. Each family has a set of triplets, in which only two children are 'identical' twins, and both have a rare developmental syndrome called Facio-audio-symphalangism (FAS).
Because none of the children carry a suspicious version of any gene implicated in FAS, Dr. Conroy reasoned that their cases might trace to a previously unsuspected part of the genome.  Moreover, she wondered whether the same part of the genome might also play a key role in the familiar, but biologically mysterious, process of twinning.  
Scientists have long noted that twinning runs in some families, suggesting that it may involve heritable genetic variation. Despite millennia of fascination, however, human twinning is still poorly understood.  To cast light on the two seemingly disparate phenomena of FAS and twinning, Dr. Conroy will use KnomeDISCOVERY™ to compare the genes of one twin from each of the two FAS families in order to identify distinctive spelling variants that could cause the disease. In the process, her research may also advance our understanding of the biology of twinning.
"The analysis of novel variants and their potential involvement in the development of FAS will be crucial," noted Conroy. "The interpretation application may prove to be a very useful tool. Also, the input and advice from individuals at Knome is always appreciated."