Linkage disequilibrium and haplotype homozygosity in population samples genotyped at a high marker density

Hui Wang; Chia Ho Lin; Susan Service; Yuguo Chen; Nelson Freimer; Chiara Sabatti; Maria Karayiorgou; J. Louw Roos; Herman Pretorious; Gabriel Bedoya; Jorge Ospina; Andres Ruiz-Linares; António Macedo; Joana Almeida Palha; Peter Heutink; Yurii Aulchenko; Ben Oostra; Cornelia Van Duijn; Marjo Riitta Jarvelin; Teppo Varilo; Lynette Peddle; Proton Rahman; Giovanna Piras; Maria Monne; Leena Peltonen

doi:10.1159/000096599

Linkage disequilibrium and haplotype homozygosity in population samples genotyped at a high marker density

Hui Wang, Chia Ho Lin, Susan Service, Yuguo Chen, Nelson Freimer, Chiara Sabatti, Maria Karayiorgou, J. Louw Roos, Herman Pretorious, Gabriel Bedoya, Jorge Ospina, Andres Ruiz-Linares, António Macedo, Joana Almeida Palha, Peter Heutink, Yurii Aulchenko, Ben Oostra, Cornelia Van Duijn, Marjo Riitta Jarvelin, Teppo VariloLynette Peddle, Proton Rahman, Giovanna Piras, Maria Monne, Leena Peltonen

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	175-189
Number of pages	15
Journal	Human Heredity
Volume	62
Issue number	4
DOIs	https://doi.org/10.1159/000096599
State	Published - Dec 2006

Keywords

Copy number variation
Genomic loss
Inbreeding
Linkage disequilibrium measures
Population genetics

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Online availability

10.1159/000096599

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Wang, H., Lin, C. H., Service, S., Chen, Y., Freimer, N., Sabatti, C., Karayiorgou, M., Roos, J. L., Pretorious, H., Bedoya, G., Ospina, J., Ruiz-Linares, A., Macedo, A., Palha, J. A., Heutink, P., Aulchenko, Y., Oostra, B., Van Duijn, C., Jarvelin, M. R., ... Peltonen, L. (2006). Linkage disequilibrium and haplotype homozygosity in population samples genotyped at a high marker density. Human Heredity, 62(4), 175-189. https://doi.org/10.1159/000096599

Wang, H, Lin, CH, Service, S, Chen, Y, Freimer, N, Sabatti, C, Karayiorgou, M, Roos, JL, Pretorious, H, Bedoya, G, Ospina, J, Ruiz-Linares, A, Macedo, A, Palha, JA, Heutink, P, Aulchenko, Y, Oostra, B, Van Duijn, C, Jarvelin, MR, Varilo, T, Peddle, L, Rahman, P, Piras, G, Monne, M & Peltonen, L 2006, 'Linkage disequilibrium and haplotype homozygosity in population samples genotyped at a high marker density', Human Heredity, vol. 62, no. 4, pp. 175-189. https://doi.org/10.1159/000096599

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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.",

keywords = "Copy number variation, Genomic loss, Inbreeding, Linkage disequilibrium measures, Population genetics",

author = "Hui Wang and Lin, {Chia Ho} and Susan Service and Yuguo Chen and Nelson Freimer and Chiara Sabatti and Maria Karayiorgou and Roos, {J. Louw} and Herman Pretorious and Gabriel Bedoya and Jorge Ospina and Andres Ruiz-Linares and Ant{\'o}nio Macedo and Palha, {Joana Almeida} and Peter Heutink and Yurii Aulchenko and Ben Oostra and {Van Duijn}, Cornelia and Jarvelin, {Marjo Riitta} and Teppo Varilo and Lynette Peddle and Proton Rahman and Giovanna Piras and Maria Monne and Leena Peltonen",

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doi = "10.1159/000096599",

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T1 - Linkage disequilibrium and haplotype homozygosity in population samples genotyped at a high marker density

AU - Wang, Hui

AU - Lin, Chia Ho

AU - Service, Susan

AU - Chen, Yuguo

AU - Freimer, Nelson

AU - Sabatti, Chiara

AU - Karayiorgou, Maria

AU - Roos, J. Louw

AU - Pretorious, Herman

AU - Bedoya, Gabriel

AU - Ospina, Jorge

AU - Ruiz-Linares, Andres

AU - Macedo, António

AU - Palha, Joana Almeida

AU - Heutink, Peter

AU - Aulchenko, Yurii

AU - Oostra, Ben

AU - Van Duijn, Cornelia

AU - Jarvelin, Marjo Riitta

AU - Varilo, Teppo

AU - Peddle, Lynette

AU - Rahman, Proton

AU - Piras, Giovanna

AU - Monne, Maria

AU - Peltonen, Leena

PY - 2006/12

Y1 - 2006/12

N2 - 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.

AB - 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.

KW - Copy number variation

KW - Genomic loss

KW - Inbreeding

KW - Linkage disequilibrium measures

KW - Population genetics

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JO - Human Heredity

JF - Human Heredity

IS - 4

ER -

Linkage disequilibrium and haplotype homozygosity in population samples genotyped at a high marker density

Abstract

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