Medicine and Health Sciences Commons^™

Cost-Effectiveness Frameworks For Comparing Genome And Exome Sequencing Versus Conventional Diagnostic Pathways: A Scoping Review And Recommended Methods, Bart S Ferket, Zach Baldwin, Priyanka Murali, Akila Pai, Kathleen F Mittendorf, Heidi V Russell, Flavia Chen, Frances L Lynch, Kristen Hassmiller Lich, Lucia A Hindorff, Renate Savich, Anne Slavotinek, Hadley Stevens Smith, Bruce D Gelb, David L Veenstra

Journal Articles

PURPOSE: Methodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES.

METHODS: We conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening.

RESULTS: Reflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses …

Centers For Mendelian Genomics: A Decade Of Facilitating Gene Discovery, Samantha M Baxter, Jennifer E Posey, Nicole J Lake, Nara Sobreira, Jessica X Chong, Steven Buyske, Elizabeth E Blue, Lisa H Chadwick, Zeynep H Coban-Akdemir, Kimberly F Doheny, Colleen P Davis, Monkol Lek, Christopher Wellington, Shalini N Jhangiani, Mark Gerstein, Richard A Gibbs, Richard P Lifton, Daniel G Macarthur, Tara C Matise, James R Lupski, David Valle, Michael J Bamshad, Ada Hamosh, Shrikant Mane, Deborah A Nickerson, Heidi L Rehm, Anne O'Donnell-Luria

Journal Articles

PURPOSE: Mendelian disease genomic research has undergone a massive transformation over the past decade. With increasing availability of exome and genome sequencing, the role of Mendelian research has expanded beyond data collection, sequencing, and analysis to worldwide data sharing and collaboration.

METHODS: Over the past 10 years, the National Institutes of Health-supported Centers for Mendelian Genomics (CMGs) have played a major role in this research and clinical evolution.

RESULTS: We highlight the cumulative gene discoveries facilitated by the program, biomedical research leveraged by the approach, and the larger impact on the research community. Beyond generating a list of gene-phenotype relationships …

Exome Sequence Association Study Of Levels And Longitudinal Change Of Cardiovascular Risk Factor Phenotypes In European Americans And African Americans From The Atherosclerosis Risk In Communities Study, Elena V Feofanova, Elise Lim, Han Chen, Minjae Lee, Ching-Ti Liu, L Adrienne Cupples, Eric Boerwinkle

Journal Articles

Cardiovascular disease (CVD) is responsible for 31% of all deaths worldwide. Among CVD risk factors are age, race, increased systolic blood pressure (BP), and dyslipidemia. Both BP and blood lipids levels change with age, with a dose-dependent relationship between the cumulative exposure to hyperlipidemia and the risk of CVD. We performed an exome sequence association study using longitudinal data with up to 7805 European Americans (EAs) and 3171 African Americans (AAs) from the Atherosclerosis Risk in Communities (ARIC) study. We assessed associations of common (minor allele frequency > 5%) nonsynonymous and splice-site variants and gene-based sets of rare variants with levels …

Is Whole-Exome Sequencing An Ethically Disruptive Technology? Perspectives Of Pediatric Oncologists And Parents Of Pediatric Patients With Solid Tumors., Laurence B Mccullough, Melody J Slashinski, Amy L Mcguire, Richard L Street, Christine M Eng, Richard A Gibbs, D William Parsons, Sharon E Plon

Faculty Publications

BACKGROUND: It has been anticipated that physician and parents will be ill prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive.

PROCEDURE: As a part of the Baylor Advancing Sequencing in Childhood Cancer Care study, we conducted semistructured interviews with 16 pediatric oncologists and 40 parents of pediatric patients with cancer prior to the return of sequencing results. We elicited expectations and attitudes concerning the impact of sequencing on clinical decision making, clinical utility, and treatment expectations from both groups. Using accepted methods of qualitative research to analyze interview transcripts, we completed a thematic analysis …

Identification Of A Novel Gene On 10q22.1 Causing Autosomal Dominant Retinitis Pigmentosa (Adrp)., Stephen P Daiger, Lori S Sullivan, Sara J Bowne, Daniel C Koboldt, Susan H Blanton, Dianna K Wheaton, Cheryl E Avery, Elizabeth D Cadena, Robert K Koenekoop, Robert S Fulton, Richard K Wilson, George M Weinstock, Richard A Lewis, David G Birch

Faculty Publications

Whole-genome linkage mapping identified a region on chromosome 10q21.3-q22.1 with a maximum LOD score of 3.0 at 0 % recombination in a six-generation family with autosomal dominant retinitis pigmentosa (adRP). All known adRP genes and X-linked RP genes were excluded in the family by a combination of methods. Whole-exome next-generation sequencing revealed a missense mutation in hexokinase 1, HK1 c.2539G > A, p.Glu847Lys, tracking with disease in all affected family members. One severely-affected male is homozygous for this region by linkage analysis and has two copies of the mutation. No other potential mutations were detected in the linkage region nor were …