Novel multilocus measure of linkage disequilibrium to estimate past effective population size.

Linkage disequilibrium (LD) between densely spaced, polymorphic genetic markers in humans and other species contains information about historical population size. Inferring past population size is of interest both from an evolutionary perspective (e.g., testing the "out of Africa" hypothesis of human evolution) and to improve models for mapping of disease and quantitative trait genes. We propose a novel multilocus measure of LD, the chromosome segment homozygosity (CSH). CSH is defined for a specific chromosome segment, up to the full length of the chromosome. In computer simulations CSH was generally less variable than the r(2) measure of LD, and variability of CSH decreased as the number of markers in the chromosome segment was increased. The essence and utility of our novel measure is that CSH over long distances reflects recent effective population size (N), whereas CSH over small distances reflects the effective size in the more distant past. We illustrate the utility of CSH by calculating CSH from human and dairy cattle SNP and microsatellite marker data, and predicting N at various times in the past for each species. Results indicated an exponentially increasing N in humans and a declining N in dairy cattle. CSH is a valuable statistic for inferring population histories from haplotype data, and has implications for mapping of disease loci.

• Publication year

  2003

• Venue

  Genome Research

• Publication date

  2003-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1101/GR.387103PMID 12654718PMCID PMC430161
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Applying CSH to human and dairy cattle SNP and microsatellite marker data yielded predictions of exponentially increasing effective population size in humans and declining effective population size in dairy cattle.

  Confidence 0.94

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review
• CSH over long distances is described as reflecting recent effective population size, whereas CSH over short distances reflects the effective size in the more distant past.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review
• In computer simulations, CSH was generally less variable than the r(2) measure of linkage disequilibrium, and its variability decreased as more markers were included in the chromosome segment.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review
• CSH is introduced as a novel multilocus measure of linkage disequilibrium defined for a specific chromosome segment, up to the full length of the chromosome.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review

• chromosome segment homozygosity

  statistic

  A multilocus linkage disequilibrium statistic defined for a chosen chromosome segment, potentially extending across an entire chromosome.

  Aliases: CSH

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review
• effective population size

  population genetics parameter

  The ancestral population-size parameter denoted by N and inferred from CSH at different time depths.

  Aliases: N, Ne

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review
• haplotype data

  dataset

  Genetic data organized by haplotypes and used as the input context for computing CSH and inferring population history.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review
• human and dairy cattle marker data

  dataset

  The human and dairy cattle SNP and microsatellite marker datasets used to apply CSH in the reported examples.

  Aliases: human and dairy cattle SNP and microsatellite marker data

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review
• linkage disequilibrium

  population genetics concept

  Nonrandom association among genetic markers on a chromosome, used here as the broader class of association that CSH measures.

  Aliases: LD

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review
• r(2) measure of ld

  statistic

  The standard pairwise linkage disequilibrium statistic used in the abstract as a comparison measure for CSH.

  Aliases: r^2, r(2)

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAnonymous (12632b8b5f) reviewGahyoun (29ua5897xm) review

• Homozygosity and linkage disequilibrium.

  2002cited by this paper
• Linkage disequilibrium in the human genome

  2001cited by this paper
• Prediction of identity by descent probabilities from marker-haplotypes

  2001cited by this paper
• Linkage disequilibrium in humans: models and data.

  2001cited by this paper
• The value of isolated populations

  2001cited by this paper
• The use of intraallelic variability for testing neutrality and estimating population growth rate.

  2001influential reference
• Single nucleotide polymorphism and linkage disequilibrium within the TCR alpha/delta locus.

  2000cited by this paper
• Single nucleotide polymorphism and linkage disequilibrium within the TCR α/δ locus

  2000cited by this paper
• Maximum likelihood estimation of population growth rates based on the coalescent.

  1998cited by this paper
• Genetic data analysis II

  1997cited by this paper
• Estimates of inbreeding and relationship among registered Holstein females in the United States.

  1996cited by this paper
• Genetic Data Analysis II . By Bruce S. Weir, Sunderland, Massachusetts. Sinauer Associates, Inc.445 pages. ISBN 0-87893-902-4.

  1996cited by this paper
• A comparison of linkage disequilibrium measures for fine-scale mapping.

  1995cited by this paper
• VNTR allele frequency distributions under the stepwise mutation model: a computer simulation approach.

  1993cited by this paper
• The sampling distribution of linkage disequilibrium under an infinite allele model without selection.

  1985influential reference
• On the genealogy of large populations

  1982cited by this paper
• Estimation of effective population size from data on linkage disequilibrium

  1981influential reference
• Effect of mating structure on variation in linkage disequilibrium.

  1980cited by this paper
• Linkage disequilibrium and homozygosity of chromosome segments in finite populations.

  1971cited by this paper
• THE NUMBER OF ALLELES THAT CAN BE MAINTAINED IN A FINITE POPULATION.

  1964cited by this paper

• INFLUENCE OF PHENOTYPING TRUNCATION ON GENETIC PARAMETER ESTIMATE AND GENOMIC PREDICTION OF PRODUCTIVE TRAITS IN NELLORE CATTLE

  2026cites this paper
• A comprehensive genomic characterization of Nellore cattle.

  2026cites this paper
• Effective Population Size Estimation in Large Marine Populations: Considering Current Challenges and Opportunities When Simulating Large Data Sets With High‐Density Genomic Information

  2025cites this paper
• Potato dihaploids uncover diverse alleles to facilitate diploid potato breeding

  2025cites this paper
• Genomic insights into runs of homozygosity, effective population size and selection signatures in Iranian meat and dairy sheep breeds

  2025cites this paper
• Evaluation of genomic selection models using whole genome sequence data and functional annotation in Belgian Blue cattle

  2025cites this paper
• Review: Assessing available genetic diversity estimates of rare breeds of livestock

  2025cites this paper
• Integration of Multiomics Data Reveals Selection Characteristics of ITGB1 That Are Associated with Size Differentiation in Pigs

  2025cites this paper
• Genomic Rewilding of Domestic Animals: The Role of Hybridization and Selection in Wolfdog Breeds

  2025cites this paper
• Systematic benchmarking of tools for structural variation detection using short- and long-read sequencing data in pigs

  2025cites this paper
• Estimating Linkage Disequilibrium and Effective Population Size Across Generations in Holstein Cattle

  2025influential citation
• Genome scan for runs of homozygosity in Saanen goats selected under tropical environments reveals candidate genes for adaptive and production traits

  2025cites this paper
• The genetic architecture of temperature-induced partial fertility restoration in A1 cytoplasm in sorghum (Sorghum bicolor (L.) Moench)

  2025cites this paper
• USING GWAS (GENOME WIDE ASSOCIATION STUDIES) FOR GENETIC IMPROVEMENT OF ECONOMIC CHARACTERS IN BUFFALO: A REVIEW ARTICLE

  2025cites this paper
• Comparative genomic insights into adaptation, selection signatures, and population dynamics in indigenous Indian sheep and foreign breeds

  2025cites this paper
• Accounting for population structure and data quality in demographic inference with linkage disequilibrium methods

  2025cites this paper
• Analysis of Genetic Diversity in Romanian Carpatina Goats Using SNP Genotyping Data

  2024cites this paper
• Exploring the genetic origin of Brazilian Locally Adapted breeds: admixture, population history and relationship with Portuguese and indicine cattle

  2024cites this paper
• Genomic structure analysis and construction of DNA fingerprint for four sheep populations.

  2024cites this paper
• Inbreeding depression is associated with recent homozygous-by-descent segments in Belgian Blue beef cattle

  2024cites this paper
• Genome-wide mining of diversity and evolutionary signatures reveals selective hotspots in Indian Sahiwal cattle.

  2024cites this paper
• Whole-genome resequencing deciphers patterns of genetic diversity, phylogeny, and evolutionary dynamics in Kashmir cattle.

  2024cites this paper
• Biases in ARG-Based Inference of Historical Population Size in Populations Experiencing Selection

  2024cites this paper
• Effective population size in field pea

  2024cites this paper
• Comprehensive whole-genome resequencing unveils genetic diversity and selective signatures of the Xiangdong black goat

  2024cites this paper
• Evaluation of heritability partitioning approaches in livestock populations

  2024cites this paper
• Comparing Genetic Ne Reconstructions Over Time With Long‐Time Wolf Monitoring Data in Two Populations

  2024cites this paper
• Estimation of contemporary effective population size in plant populations: Limitations of genomic datasets

  2024cites this paper
• The effect of new and ancestral inbreeding on milk production traits in Iranian Holstein cattle.

  2023cites this paper
• Genomic characterization of Serbian Holstein-Friesian cattle population

  2023cites this paper
• Impact of population structure in the estimation of recent historical effective population size by the software GONE

  2023cites this paper
• Population structure, runs of homozygosity analysis and construction of single nucleotide polymorphism fingerprinting database of Longnan goat population

  2023cites this paper
• Comparative assessment of the effective population size and linkage disequilibrium of Karan Fries cattle revealed viable population dynamics

  2023cites this paper
• Linkage disequilibrium and effective population size in Indian goat breeds

  2023cites this paper
• Sources of coaster brook trout (Salvelinus fontinalis) revealed by genomic analysis of brook trout populations along Minnesota’s shoreline with Lake Superior

  2023cites this paper
• A genetic linkage map of the threatened catfish Lophiosilurus alexandri: Inferences on effective population size

  2023cites this paper
• Genomic characterization and population structure of Croatian Arabian horse

  2023cites this paper
• An empirical test of the estimation of historical effective population size using Drosophila melanogaster

  2023cites this paper
• Genomic diversity and population structure of the Czech Holstein cattle

  2023cites this paper
• Pedigree reconstruction and population structure using SNP markers in Gir cattle

  2023cites this paper
• Population genomics of American mink using genotype data

  2023cites this paper
• Assessment of runs of homozygosity, heterozygosity-rich regions and genomic inbreeding estimates in a subpopulation of Guzerá (Bos indicus) dual-purpose cattle.

  2023cites this paper
• Estimation of the contemporary effective population size from SNP data while accounting for mating structure

  2023cites this paper
• Genome-wide study of linkage disequilibrium, population structure, and inbreeding in Iranian indigenous sheep breeds

  2023cites this paper
• Integrating genome-wide association studies and population genomics analysis reveals the genetic architecture of growth and backfat traits in pigs

  2022cites this paper
• Simulation-Based Evaluation of Methods, Data Types, and Temporal Sampling Schemes for Detecting Recent Population Declines

  2022cites this paper
• Estimating the effective population size of Swedish native cattle

  2022cites this paper
• Genetic diversity of two native sheep breeds by genome-wide analysis of single nucleotide polymorphisms.

  2022cites this paper
• Simultaneous testing of rule- and model-based approaches for runs of homozygosity detection opens up a window into genomic footprints of selection in pigs

  2022cites this paper
• Natural adaptation and human selection of northeast African sheep genomes.

  2022cites this paper
• Genetic diversity in some domestic and wild sheep and goats in Iran

  2022cites this paper
• Estimates of Effective Population Size in Commercial and Hatchery Strains of Coho Salmon (Oncorhynchus kisutch (Walbaum, 1792))

  2022cites this paper
• Development of a High-Density 665 K SNP Array for Rainbow Trout Genome-Wide Genotyping

  2022cites this paper
• Local selection signals in the genome of blue tits emphasize regulatory and neuronal evolution

  2022influential citation
• Development of genomic predictions for Angus cattle in Brazil incorporating genotypes from related American sires

  2022influential citation
• Genotype–environment interaction for milk production of Gyr cattle in Brazil and Colombia

  2022cites this paper
• High-resolution genomic analysis of four local Vietnamese chicken breeds.

  2022cites this paper
• The estimates of effective population size based on linkage disequilibrium are virtually unaffected by natural selection

  2022cites this paper
• 526. Candidate genes for milk, growth and immune system traits in Brazilian Iberian-derived locally adapted cattle breeds

  2022cites this paper
• Prediction ability for growth and maternal traits using SNP arrays based on different marker densities in Nellore cattle using the ssGBLUP

  2022cites this paper
• 226. Candidate genes for disease, reproduction and meat quality traits in Portuguese native breeds

  2022cites this paper
• Single nucleotide polymorphism-based analysis of the genetic structure of the Min pig conserved population

  2022cites this paper
• Estimates of genomic inbreeding and identification of candidate regions in Beijing-You chicken populations.

  2022cites this paper
• The genomic structure of isolation across breed, country and strain for important South African and Australian sheep populations

  2022cites this paper
• Pig Breeding for Increased Sustainability

  2022cites this paper
• Natural selection does not affect the estimates of effective population size based on linkage disequilibrium

  2021cites this paper
• Linkage disequilibrium and effective population size in Brazilian Saanen goats

  2021cites this paper
• Genome-Wide Analyses Reveal the Genetic Architecture and Candidate Genes of Indicine, Taurine, Synthetic Crossbreds, and Locally Adapted Cattle in Brazil

  2021cites this paper
• Estimates of genomic inbreeding and identification of candidate regions that differ between Chinese indigenous sheep breeds

  2021cites this paper
• Неравновесное сцепление (гаметическое неравновесие) структурных генов в популяции крупного рогатого скота

  2021cites this paper
• Application of a novel 50K SNP genotyping array to assess the genetic diversity and linkage disequilibrium in a farmed Pacific white shrimp (Litopenaeus vannamei) population

  2021cites this paper
• Genetic diversity and effective population sizes of thirteen Indian cattle breeds

  2021cites this paper
• Genetic diversity and the application of runs of homozygosity-based methods for inbreeding estimation in German White-headed Mutton sheep

  2021cites this paper
• Food Resources Biodiversity: The Case of Local Cattle in Slovakia

  2021cites this paper
• A Comprehensive Comparison of Haplotype-Based Single-Step Genomic Predictions in Livestock Populations With Different Genetic Diversity Levels: A Simulation Study

  2021cites this paper
• Formation of the genetic structure of cattle populations by single locus DNA fragments depending on their productivity direction and origin

  2021cites this paper
• Population Genomics of American Mink Using Whole Genome Sequencing Data

  2021cites this paper
• Development of polymorphic markers in the immune gene complex loci of cattle.

  2021cites this paper
• Genetic diversity and genomic inbreeding in Japanese Black cows in the islands of Okinawa Prefecture evaluated using single-nucleotide polymorphism array.

  2021cites this paper
• Genetic Background and Inbreeding Depression in Romosinuano Cattle Breed in Mexico

  2021cites this paper
• Population structure, inbreeding and admixture in local cattle populations managed by community‐based breeding programs in Burkina Faso

  2021cites this paper
• Genomic inbreeding and selection signatures in the local dairy breed Icelandic Cattle.

  2021cites this paper
• The natural adaptation and human selection history of African sheep genomes

  2021cites this paper
• Navigating the temporal continuum of effective population size

  2021cites this paper
• The pattern of linkage disequilibrium in Dual-Purpose Belgian Blue cattle.

  2021cites this paper
• Genetic Diversity and Signatures of Selection for Thermal Stress in Cattle and Other Two Bos Species Adapted to Divergent Climatic Conditions

  2021cites this paper
• Linkage Disequilibrium and Effective Population Size of Buffalo Populations of Iran, Turkey, Pakistan, and Egypt Using a Medium Density SNP Array

  2021cites this paper
• Exploring the size of reference population for expected accuracy of genomic prediction using simulated and real data in Japanese Black cattle

  2021cites this paper
• Genome-wide structural variations in Brazilian Senepol cattle, a tropically adapted taurine breed

  2021cites this paper
• Contemporary N e estimation using temporally spaced data with linked loci

  2021cites this paper
• Disequilibrium linkage (gametic disequilibrium) of structural genes in the bovine population

  2021cites this paper
• Estimates of recent and historical effective population size in turbot, seabream, seabass and carp selective breeding programmes

  2021influential citation
• Ethiopian indigenous goats offer insights into past and recent demographic dynamics and local adaptation in sub‐Saharan African goats

  2020cites this paper
• Accuracy of genomic evaluation using imputed high-density genotypes for carcass traits in commercial Hanwoo population

  2020cites this paper
• Conservation Assessment of the State Goat Farms by Using SNP Genotyping Data

  2020cites this paper
• ArticleGenome-Wide Diversity

  2020cites this paper
• Recent demographic history inferred by high-resolution analysis of linkage disequilibrium.

  2020influential citation
• High-density single nucleotide polymorphism chip-based conservation genetic analysis of indigenous pig breeds from Shandong Province, China

  2020cites this paper
• Estimation of Linkage Disequilibrium and Effective Population Size in Three Italian Autochthonous Beef Breeds

  2020cites this paper
• A beginner's guide to low‐coverage whole genome sequencing for population genomics

  2020cites this paper