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      Prediction of Total Genetic Value Using Genome-Wide Dense Marker Maps

      1 , 2 , 2 , 3
      Genetics
      Oxford University Press (OUP)

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          Abstract

          Recent advances in molecular genetic techniques will make dense marker maps available and genotyping many individuals for these markers feasible. Here we attempted to estimate the effects of ∼50,000 marker haplotypes simultaneously from a limited number of phenotypic records. A genome of 1000 cM was simulated with a marker spacing of 1 cM. The markers surrounding every 1-cM region were combined into marker haplotypes. Due to finite population size (Ne = 100), the marker haplotypes were in linkage disequilibrium with the QTL located between the markers. Using least squares, all haplotype effects could not be estimated simultaneously. When only the biggest effects were included, they were overestimated and the accuracy of predicting genetic values of the offspring of the recorded animals was only 0.32. Best linear unbiased prediction of haplotype effects assumed equal variances associated to each 1-cM chromosomal segment, which yielded an accuracy of 0.73, although this assumption was far from true. Bayesian methods that assumed a prior distribution of the variance associated with each chromosome segment increased this accuracy to 0.85, even when the prior was not correct. It was concluded that selection on genetic values predicted from markers could substantially increase the rate of genetic gain in animals and plants, especially if combined with reproductive techniques to shorten the generation interval.

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          Most cited references22

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          Introduction to Quantitative Genetics

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            Recovery of inter-block information when block sizes are unequal

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              Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.

              Sequence variation in human genes is largely confined to single-nucleotide polymorphisms (SNPs) and is valuable in tests of association with common diseases and pharmacogenetic traits. We performed a systematic and comprehensive survey of molecular variation to assess the nature, pattern and frequency of SNPs in 75 candidate human genes for blood-pressure homeostasis and hypertension. We assayed 28 Mb (190 kb in 148 alleles) of genomic sequence, comprising the 5' and 3' untranslated regions (UTRs), introns and coding sequence of these genes, for sequence differences in individuals of African and Northern European descent using high-density variant detection arrays (VDAs). We identified 874 candidate human SNPs, of which 22% were confirmed by DNA sequencing to reveal a discordancy rate of 21% for VDA detection. The SNPs detected have an average minor allele frequency of 11%, and 387 are within the coding sequence (cSNPs). Of all cSNPs, 54% lead to a predicted change in the protein sequence, implying a high level of human protein diversity. These protein-altering SNPs are 38% of the total number of such SNPs expected, are more likely to be population-specific and are rarer in the human population, directly demonstrating the effects of natural selection on human genes. Overall, the degree of nucleotide polymorphism across these human genes, and orthologous great ape sequences, is highly variable and is correlated with the effects of functional conservation on gene sequences.
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                Author and article information

                Journal
                Genetics
                Oxford University Press (OUP)
                1943-2631
                April 01 2001
                April 01 2001
                April 01 2001
                April 01 2001
                April 01 2001
                : 157
                : 4
                : 1819-1829
                Affiliations
                [1 ]Research Institute of Animal Science and Health, 8200 AB Lelystad, The Netherlands
                [2 ]Victorian Institute of Animal Science, Attwood 3049, Victoria, Australia
                [3 ]Institute of Land and Food Resources, University of Melbourne, Parkville 3052, Victoria, Australia
                Article
                10.1093/genetics/157.4.1819
                11290733
                d969c829-5a0f-41f4-87a0-ab725a83a89d
                © 2001

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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