Steven M Lipkin1, Laura S Rozek2, 3, Gad Rennert4, Wei Yang5, Peng-Chieh Chen1, Joseph Hacia6, Nathan Hunt6, Brian Shin1, Steve Fodor7, Mark Kokoris8, Joel K Greenson9, Eric Fearon2, 9, 10, Henry Lynch11, Francis Collins12
& Stephen B Gruber21
Divisions of Oncology and Epidemiology, Departments of Medicine and Biological Chemistry, University of California, Irvine, Irvine, California 92697, USA.
2
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
3
Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
4
Department of Community Medicine and Epidemiology Carmel Medical Center and Technion Faculty of Medicine Haifa, Israel.
5
Molecular Structure Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
6
The Institute for Genetic Medicine, University of Southern California, Los Angeles, California 90089, USA.
7
Affymetrix Corporation, Santa Clara, California 95051, USA.
8
BioCaptus, Bothell, Washington 99164, USA.
9
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
10
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
11
Hereditary Cancer Institute, Creighton University. Omaha, Nebraska 50035, USA.
12
Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
Correspondence should be addressed to Steven M Lipkin slipkin@uci.edu or Stephen B Gruber sgruber@med.umich.edu
C, resulting in the amino acid substitution D132H) in 
1.3% of Israeli individuals with CRC self-described as Jewish, Christian and Muslim. MLH1 415C confers clinically significant susceptibility to CRC. In contrast to classic HNPCC, CRCs associated with MLH1 415C usually do not have the MSI defect, which is important for clinical mutation screening. Structural and functional analyses showed that the normal ATPase function of MLH1 is attenuated, but not eliminated, by the MLH1 415G
