Whole-genome resequencing of two elite sires for the detection of haplotypes under selection in dairy cattle

Larkin, Denis M.; Daetwyler, Hans D.; Hernandez, Alvaro G.; Wright, Chris; Hetrick, Lorie A.; Boucek, Lisa; Bachman, Sharon L.; Band, Mark; Akraiko, Tatsiana V.; Cohen, Miri; Thimmapuram, Jyothi; MacLeod, Iona M.; Harkins, Timothy T.; McCague, Jennifer E.; Goddard, Michael E.; Hayes, Ben J.; Lewin, Harris A.

doi:10.1073/pnas.1114546109

Cited by 70 publications

(69 citation statements)

References 34 publications

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“…The SNP on these arrays, primarily selected using spacing along the genome and allele frequency (Matukumalli et al, 2009;Ramos et al, 2009), are ef- Table 6. Genetic correlations between genomic EBV trained by GPE Cycle VII shear force measurements, using whole-genome and sets selected by functional annotation and association with phenotype, and 14-d slice shear force measured on steers from Cycle VIII and continuous GPE 1 (Cánovas et al, 2010;Stothard et al, 2011;Larkin et al, 2012). Categorizing these variants according to expected effect on annotated protein coding genes may reveal the variants most infl uential to gene function (McLaren et al, 2010;Cingolani et al, 2012).…”

Section: Future Effortsmentioning

confidence: 99%

BREEDING AND GENETICS SYMPOSIUM: Networks and pathways to guide genomic selection1–3

Snelling

Cushman

Keele

et al. 2013

Journal of Animal Science

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Many traits affecting profi tability and sustainability of meat, milk, and fi ber production are polygenic, with no single gene having an overwhelming infl uence on observed variation. No knowledge of the specifi c genes controlling these traits has been needed to make substantial improvement through selection. Signifi cant gains have been made through phenotypic selection enhanced by pedigree relationships and continually improving statistical methodology. Genomic selection, recently enabled by assays for dense SNP located throughout the genome, promises to increase selection accuracy and accelerate genetic improvement by emphasizing the SNP most strongly correlated to phenotype although the genes and sequence variants affecting phenotype remain largely unknown. These genomic predictions theoretically rely on linkage disequilibrium (LD) between genotyped SNP and unknown functional variants, but familial linkage may increase effectiveness when predicting individuals related to those in the training data. Genomic selection with functional SNP genotypes should be less reliant on LD patterns shared by training and target populations, possibly allowing robust prediction across unrelated populations.

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Section: Future Effortsmentioning

confidence: 99%

BREEDING AND GENETICS SYMPOSIUM: Networks and pathways to guide genomic selection1–3

Snelling

Cushman

Keele

et al. 2013

Journal of Animal Science

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“…To inform the simulation of sequence data for the founders of this population, we relied on the work of Macleod et al (2012A), which used multilocus patterns of LD in whole-genome sequence from two Holstein founder bulls (Larkin et al, 2012) to reconstruct population genetic history. Based on this population history (with variable effective population size), Macleod et al (2012B) simulated sequence data that closely matched the multilocus LD patterns in the founder bull sequences.…”

Section: Data Simulationmentioning

confidence: 99%

Toward genomic prediction from whole-genome sequence data: impact of sequencing design on genotype imputation and accuracy of predictions

2013

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Genomic prediction from whole-genome sequence data is attractive, as the accuracy of genomic prediction is no longer bounded by extent of linkage disequilibrium between DNA markers and causal mutations affecting the trait, given the causal mutations are in the data set. A cost-effective strategy could be to sequence a small proportion of the population, and impute sequence data to the rest of the reference population. Here, we describe strategies for selecting individuals for sequencing, based on either pedigree relationships or haplotype diversity. Performance of these strategies (number of variants detected and accuracy of imputation) were evaluated in sequence data simulated through a real Belgian Blue cattle pedigree. A strategy (AHAP), which selected a subset of individuals for sequencing that maximized the number of unique haplotypes (from single-nucleotide polymorphism panel data) sequenced gave good performance across a range of variant minor allele frequencies. We then investigated the optimum number of individuals to sequence by fold coverage given a maximum total sequencing effort. At 600 total fold coverage (x 600), the optimum strategy was to sequence 75 individuals at eightfold coverage. Finally, we investigated the accuracy of genomic predictions that could be achieved. The advantage of using imputed sequence data compared with dense SNP array genotypes was highly dependent on the allele frequency spectrum of the causative mutations affecting the trait. When this followed a neutral distribution, the advantage of the imputed sequence data was small; however, when the causal mutations all had low minor allele frequencies, using the sequence data improved the accuracy of genomic prediction by up to 30%.

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“…We had sequenced genomes of the two founders of this population and tracked the frequency of their alleles for seven generations of their direct descendants. It was expected that the population frequency of "favorable" alleles will gradually increase in areas of the genome which are acted upon by selection [5]. Two of the sequenced genomes belonged to two related bulls:…”

Section: Genes and Mutations Affecting Economically-important Traits mentioning

confidence: 99%

The genomes and history of domestic animals

Larkin

Yudin

2016

Mol. Genet. Microbiol. Virol.

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SummaryThis paper reviews how mammalian genomes are utilized in modern genetics for the detection of genes and polymorphisms (mutations) within domesticated animal (mostly livestock) genomes that are linked to traits of economic importance to humans. Examples are given of how genetic analysis allows to determine key genes associated with the quality and quantity of milk in cattle and key genes for meat production. Various questions are reviewed, such as how contemporary methods of genome sequencing allow to maximise the effective detection of genic and regulatory DNA polymorphisms within the genomes of major domesticated mammals (cattle, sheep and pigs) and the history of their formation from the standpoint of genetics. The Structure of the GenomeWithin mammalian genomes, up to 40% of the DNA is comprised of simple repeats, DNAand retro-transposons, SINE and LINE elements, most of which do not encode for proteins (Fig. 1). Out of 30% of DNA that belongs to genes, only 2% is coding DNA (exons).Heterochromatin DNA, repetitive and unique noncoding DNA sequences comprise a further 30% of the genome. Variation within DNA sequences in the genome as a result of errors during replication is the basis for natural (during evolution) or artificial (animal breeding) selection. Genes and mutations affecting economically-important traits in domesticated animalsThe principle of "candidate gene" search is presented in Fig. 2. Through the use of linkage mapping techniques, it can be determined that a specific chromosomal locus controls an economically important trait in livestock. Using the methods of comparative mapping, one can find the homeologous regions of human or mouse chromosomes corresponding to this locus. The genes that are present in human or mouse heomologous intervals are screened for ones performing a role similar to the one which is studied in the livestock animal. Gene(s) that control similar traits in a human or mouse, are then cloned and sequenced in the animal. The mutations (e.g. point mutations) are determined in these genes in livestock animal populations, and an associative analysis is conducted, which reveals the relationship (or lack thereof) between the animal's phenotype and specific nucleotide substitution(s). If an association of this sort is observed, then the gene that influences a particular trait in the animal's genome was identified correctly. Obviously, this approach has a number of drawbacks, namely: a) it "works" only for genes with similar In cases where the trait is controlled by multiple genes, the situation becomes more complicated, since often the contribution of each of these genes to the phenotype is quite small and often it is not possible to find one or two major genes/mutations that would significantly change phenotype in the desired direction. As shown in Table 1 As shown above, methods of genetic analysis allow for the identification of individual genes and mutations that have a desired effect on a number of important traits in domesticated animals. However, the traits are often...

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Whole-genome resequencing of two elite sires for the detection of haplotypes under selection in dairy cattle

Cited by 70 publications

References 34 publications

BREEDING AND GENETICS SYMPOSIUM: Networks and pathways to guide genomic selection1–3

BREEDING AND GENETICS SYMPOSIUM: Networks and pathways to guide genomic selection1–3

Toward genomic prediction from whole-genome sequence data: impact of sequencing design on genotype imputation and accuracy of predictions

The genomes and history of domestic animals

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