Original Paper

Linkage Disequilibrium and Haplotype Homozygosity in Population Samples Genotyped at a High Marker Density
Hui Wang^a, Chia-Ho Lin^a, Susan Service^b, Yuguo Chen^d, Nelson Freimer^b, Chiara Sabatti^{a, c}, The international collaborative group on isolated populations

^aDepartment of Statistics,
^bCenter for Neurobehavioral Genetics, and
^cDepartment of Human Genetics, UCLA, Los Angeles, Calif., and
^dDepartment of Statistics, University of Illinois at Urbana-Champain, Champain, Ill., USA

Address of Corresponding Author

Hum Hered 2006;62:175-189 (DOI: 10.1159/000096599)

  Key Words

• Linkage disequilibrium measures
• Inbreeding
• Copy number variation
• Population genetics
• Genomic loss

  Abstract

Objective: Analyze the information contained in homozygous haplotypes detected with high density genotyping. Methods: We analyze the genotypes of ~2,500 markers on chr 22 in 12 population samples, each including 200 individuals. We develop a measure of disequilibrium based on haplotype homozygosity and an algorithm to identify genomic segments characterized by non-random homozygosity (NRH), taking into account allele frequencies, missing data, genotyping error, and linkage disequilibrium. Results: We show how our measure of linkage disequilibrium based on homozygosity leads to results comparable to those of R², as well as the importance of correcting for small sample variation when evaluating D'. We observe that the regions that harbor NRH segments tend to be consistent across populations, are gene rich, and are characterized by lower recombination. Conclusions: It is crucial to take into account LD patterns when interpreting long stretches of homozygous markers.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Chiara Sabatti
Department of Human Genetics, UCLA School of Medicine
695 Charles E. Young Drive South
Los Angeles, CA 90095-7088 (USA)
Tel. +1 310 794 9567, Fax +1 310 794 5446, E-Mail csabatti@mednet.ucla.edu

  Article Information

The international collaborative group on isolated populations members that are not listed separately as authors of this manuscript are: Maria Karayiorgou^a, J. Louw Roos^b, Herman Pretorious^b, Gabriel Bedoya^c, Jorge Ospina^d, Andres Ruiz-Linares^{c, e}, António Macedo^f, Joana Almeida Palha^g, Peter Heutink^{h, i}, Yurii Aulchenko^j, Ben Oostra^j, Cornelia van Duijn^j, Marjo-Riitta Jarvelin^{k, l}, Teppo Varilo^{m, n}, Lynette Peddle^o, Proton Rahman^p, Giovanna Piras^q, Maria Monne^q, Leena Peltonen^{m, n}, and the affiliations: ^aRockefeller University, New York, N.Y, USA; ^bUniversity of Pretoria Weskoppies Hospital, Pretoria, Republic of South Africa; ^cLaboratorio de Genetica Molecular, Universidad de Antioquia, and ^dDepartamento de Psiquiatria, Universidad de Antioquia, Medellin, Colombia; ^eThe Galton Laboratory, Department of Biology (Wolfson House), University College London, London, UK; ^fInstituto de Psicologia Médica, Faculdade de Medicina, Coimbra, and ^gLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; ^hDepartment of Human Genetics, Section of Medical Genomics, VU University Medical Center, and ⁱCenter for Neurogenomics and Cognitive Research, VU University and VU University Medical Center, Amsterdam and ^jGenetic Epidemiology Unit, Departments of Epidemiology, Biostatistics and Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands; ^kDepartment of Public Health Science and General Practice, University of Oulu, Oulu, Finland; ^lDepartment of Epidemiology and Public Health, Imperial College London, London, UK; ^mDepartment of Medical Genetics, University of Helsinki, and ⁿDepartment of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, Helsinki, Finland; ^oNewfound Genomics, and ^pMemorial University of Newfoundland, Newfoundland, Canada; ^qDivision of Haematology, San Francesco Hospital, Nuoro, Italy.

Received: May 3, 2006
Accepted after revision: August 7, 2006
Published online: October 30, 2006
Number of Print Pages : 15
Number of Figures : 7, Number of Tables : 1, Number of References : 22