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A powerful and rapid approach to human genome scanning using small quantities of genomic DNA

Published online by Cambridge University Press:  08 June 2001

MARIAN BEEKMAN
Affiliation:
Gaubius Laboratory, TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
NICO LAKENBERG
Affiliation:
Gaubius Laboratory, TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands
STACEY S. CHERNY
Affiliation:
Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, Camberwell, London, UK
PETER DE KNIJFF
Affiliation:
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
C. CORNELIS KLUFT
Affiliation:
Gaubius Laboratory, TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands
GERT-JAN B. VAN OMMEN
Affiliation:
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
GEORGE P. VOGLER
Affiliation:
Center for Developmental and Health Genetics and Department of Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania, USA
RUNE R. FRANTS
Affiliation:
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
DORRET I. BOOMSMA
Affiliation:
Department of Psychology, Free University of Amsterdam, Amsterdam, The Netherlands
P. ELINE SLAGBOOM
Affiliation:
Gaubius Laboratory, TNO Prevention and Health, PO Box 2215, 2301 CE Leiden, The Netherlands Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
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Abstract

Dense maps of short-tandem-repeat polymorphisms (STRPs) have allowed genome-wide searches for genes involved in a great variety of diseases with genetic influences, including common complex diseases. Generally for this purpose, marker sets with a 10 cM spacing are genotyped in hundreds of individuals. We have performed power simulations to estimate the maximum possible inter-marker distance that still allows for sufficient power. In this paper we further report on modifications of previously published protocols, resulting in a powerful screening set containing 229 STRPs with an average spacing of 18·3 cM. A complete genome scan using our protocol requires only 80 multiplex PCR reactions which are all carried out using one set of conditions and which do not contain overlapping marker allele sizes. The multiplex PCR reactions are grouped by sets of chromosomes, which enables on-line statistical analysis of a set of chromosomes, as sets of chromosomes are being genotyped. A genome scan following this modified protocol can be performed using a maximum amount of 2·5 μg of genomic DNA per individual, isolated from either blood or from mouth swabs.

Type
Research Paper
Copyright
© 2001 Cambridge University Press
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