Linkage-Disequilibrium Mapping Without Genotyping
Vivian G. Cheung1,
Jeffrey P. Gregg2,
Kathryn J. Gogolin-Ewens3,
Jonathan Bandong1,
Charles A. Stanley4,
Lester Baker4,
Michael J. Higgins5,
Norma J. Nowak5,
Thomas B. Shows5,
Warren J. Ewens6,
Stanley F. Nelson7
and Richard S. Spielman3
Divisions of 1 Neurology and 4 Endocrinology,
Department of Pediatrics, The Children's Hospital of Philadelphia,
Philadelphia, Pennsylvania 19104, USA.
Departments of 2 Pathology, 7
Pediatrics and Biological Chemistry, University of California, Los Angeles,
California 90095, USA.
Department of 3 Genetics, 6 Biology,
University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
5
Department of Human Genetics, Roswell Park Cancer Institute,
Buffalo, New York 14263, USA.
Correspondence should be addressed to V.G.C.
e-mail:
vcheung@mail.med.upenn.edu
Nature Genetics,
18 (3), 225-230 (March 1998 )
Abstract
Genomic mismatch scanning (GMS) is a technique that
enriches for regions of identity by descent (IBD) between
two individuals without the need for genotyping or
sequencing. Regions of IBD selected by GMS are
mapped by hybridization to a microarray containing
ordered clones of genomic DNA from chromosomes of
interest. Here we demonstrate the feasibility and efficacy
of this form of linkage-mapping, using congenital
hyperinsulinism (HI), an autosomal recessive disease,
whose relatively high frequency in Ashkenazi Jews
suggests a founder effect. The gene responsible (SUR1)
encodes the sulfonylurea receptor, which maps to
chromosome 11p15.1. We show that the combination of
GMS and hybridization of IBD products to a
chromosome-11 microarray correctly maps the HI gene to
a 2-Mb region, thereby demonstrating
linkage-disequilibrium mapping without genotyping.
Association Studies