Mary-Claire King
phone: (206) 616-4294
fax: (206) 616-4295
Health Sciences K-160
Box 357720
mcking [ a t ] uw.edu
website
Our group uses experimental and computational approaches in studies of human families and populations in order to identify and characterize genes responsible for complex human conditions. Our primary areas of interest are inherited breast, ovarian, and prostate cancer; schizophrenia and related severe mental illness; and severe inherited disorders in children. We are particularly interested in disentangling the genetic heterogeneity of complex traits, thereby discovering clinically meaningful mutations that cause common diseases. Our philosophy is described in this commentary:
McClellan J and King M-C. Genetic heterogeneity in human disease. Cell 141:210-7, 2010
Our current projects and some recent publications are described below.
Inherited breast and ovarian cancer. Development of genomic and transcriptomic tools to discover cryptic classes of mutations; application of these approaches to previously undiagnosed families and understudied populations; biological characterization of tumor suppressor genes in the context of inherited cancer.
Recent publications:
Walsh T, et al. A CRISPR-Cas9 / long-read-sequencing approach to identify cryptic mutations in BRCA1 and other tumor suppressor genes. J Med Genet 2020 Oct15. PMID: 33060287
Casadei S*, Gulsuner S*, et al. Characterization of splice-altering mutations in inherited predisposition to cancer. Proc Natl Acad Sci USA 116: 26798-807, 2019
Walsh T, et al. Inherited predisposition to breast cancer in the Carolina Breast Cancer Study. NPJ Breast Cancer 7(1):6, 2021
Zheng Y*, Walsh T*, et al. Inherited breast cancer in Nigerian women. J Clin Oncol 36:2820-25, 2018
Norquist BM, et al. Mutations in homologous recombination genes and outcomes in ovarian carcinoma patients. Clin Cancer Res. 24:777-83, 2018
Stewart MD, et al. BARD1 is necessary for ubiquitylation of nucleosomal histone H2A and for transcriptional regulation of estrogen metabolism genes. Proc Natl Acad Sci USA 115:1316-21, 2018
Weinberg-Shukron A, et al. Essential role for BRCA2 in ovarian development and function. New Engl J Med 379:1042-49, 2018.
Genetics of schizophrenia. The role in the pathogenesis of schizophrenia of de novo and ultra-rare recent mutations in genes controlling neurodevelopment.
Recent publications:
McClellan JM, Lehner T, King M-C. Gene discovery for complex traits: Lessons from Africa.[Commentary] Cell 171:261-64, 2017
Gulsuner S, et al. Genetics of schizophrenia in the South African Xhosa. Science 367:569-73, 2020
Gulsuner S*, Walsh T*, et al. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell 154:518-529, 2013
McClellan JM, Lehner T, King M-C. Gene discovery for complex traits: Lessons from Africa.[Commentary] Cell 171:261-64, 2017
Pierce SB, et al. De novo mutation in RING1 with epigenetic effects on neurodevelopment. Proc Natl Acad Sci USA 115:1558-63, 2018
Genetic bases of pediatric diseases. Discovery and characterization of genes responsible for severe inherited disorders in children.
Recent publications:
Abu Rayyan A, et al. Genomic analysis of inherited hearing loss in the Palestinian population. Proc Natl Acad Sci USA 117:20070-76, 2020
Baxter SK, et al. Molecular diagnosis of childhood immune dysregulation, polyendocrinopathy and enteropathy; and implications for clinical management. J Allergy Clin Immunol, 2021 Apr 20. PMID: 33864888
Carlson RJ, et al. Genetic heterogeneity and core clinical features of NOG-related-symphalangism spectrum disorder. Otol Neurotol, 2021 May 26. PMID: 34049328
Seo A, et al. Inherited thrombocytopenia associated with mutation of udp-galactose-4-epimerase (GALE). Hum Molec Genet 28:133-42, 2019
Navon Elkan P*, Pierce SB*, Segel R*, et al. Mutant adenosine deaminase 2 (ADA2) in a polyarteritis nodosa vasculopathy. New Engl J Med 370:921-31, 2014
We welcome to the lab geneticists who are interested in working with us in these areas.