Sequencing in a High-Risk Chronic Lymphocytic Leukemia Pedigree

Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the U.S. and although it is treatable, the majority of patients die from their disease. A fuller understanding of how CLL arises will lead to opportunities for novel therapeutic, prevention and early detection strategies. Numerous studies indicate that heritable genetic risk factors contribute to CLL; however, none have yet been identified.

This study, led by Nicola Camp, PhD, employs unique approaches for advancing the search for rare genetic risk variants. Investigators will search for genetic risk factors using families enriched for CLL disease. The ability to identify such families is made possible by the unique and powerful Utah Population Database resource. Such families should be enriched for disease variants, making the variants easier to find.

While it is widely believed that families enriched for disease will accelerate identification of rare risk variants, there is no published data demonstrating which family relations convey the most useful sequence and statistical information, and which type of sequencing technology (whole genome or whole exome) is most powerful. An additional goal of this study is to establish a general protocol for quickly and effectively identifying rare genetic disease variants that can be broadly applied to investigations of genetic diseases.

This project will both advance knowledge of genetic risk factors for CLL and also provide an essential first step towards improving study design to ultimately advance personalized risk assessment and health care.


In this high-risk CLL pedigree, diamonds are used to maintain the anonymity of pedigree members. Black shading indicates CLL. Red circles indicate the eight individuals proposed to be sequenced.