Distribution and location of genetic effects for dairy traits
TL;DR: A high-density scan using 38,416 single nucleotide polymorphism markers for 5,285 bulls confirmed 2 previously known major genes on Bos taurus autosomes (BTA) 6 and 14 but revealed few other large effects as discussed by the authors.
About: This article is published in Journal of Dairy Science.The article was published on 2009-06-01 and is currently open access. It has received 224 citations till now. The article focuses on the topics: Quantitative trait locus & Allele.
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TL;DR: Genotypes for 38,416 markers and August 2003 genetic evaluations for 3,576 Holstein bulls born before 1999 were used to predict January 2008 daughter deviations and genomic prediction improves reliability by tracing the inheritance of genes even with small effects.
1,166 citations
TL;DR: A national single-step genetic evaluation with the pedigree relationship matrix augmented with genomic information provided genomic predictions with accuracy and bias comparable to multiple-step procedures and could account for any population or data structure.
1,095 citations
TL;DR: The 1000 bull genomes project supports the goal of accelerating the rates of genetic gain in domestic cattle while at the same time considering animal health and welfare by providing the annotated sequence variants and genotypes of key ancestor bulls.
Abstract: The 1000 bull genomes project supports the goal of accelerating the rates of genetic gain in domestic cattle while at the same time considering animal health and welfare by providing the annotated sequence variants and genotypes of key ancestor bulls. In the first phase of the 1000 bull genomes project, we sequenced the whole genomes of 234 cattle to an average of 8.3-fold coverage. This sequencing includes data for 129 individuals from the global Holstein-Friesian population, 43 individuals from the Fleckvieh breed and 15 individuals from the Jersey breed. We identified a total of 28.3 million variants, with an average of 1.44 heterozygous sites per kilobase for each individual. We demonstrate the use of this database in identifying a recessive mutation underlying embryonic death and a dominant mutation underlying lethal chrondrodysplasia. We also performed genome-wide association studies for milk production and curly coat, using imputed sequence variants, and identified variants associated with these traits in cattle.
690 citations
TL;DR: It is argued that neither theory nor data justify a view of readily discoverable large‐effect alleles as the primary molecular substrates for evolution, and that evolution often acts via large numbers of small‐effect polygenes, individually undetectable.
Abstract: The search for the alleles that matter, the quantitative trait nucleotides (QTNs) that underlie heritable variation within populations and divergence among them, is a popular pursuit. But what is the question to which QTNs are the answer? Although their pursuit is often invoked as a means of addressing the molecular basis of phenotypic evolution or of estimating the roles of evolutionary forces, the QTNs that are accessible to experimentalists, QTNs of relatively large effect, may be uninformative about these issues if large-effect variants are unrepresentative of the alleles that matter. Although 20th century evolutionary biology generally viewed large-effect variants as atypical, the field has recently undergone a quiet realignment toward a view of readily discoverable large-effect alleles as the primary molecular substrates for evolution. I argue that neither theory nor data justify this realignment. Models and experimental findings covering broad swaths of evolutionary phenomena suggest that evolution often acts via large numbers of small-effect polygenes, individually undetectable. Moreover, these small-effect variants are different in kind, at the molecular level, from the large-effect alleles accessible to experimentalists. Although discoverable QTNs address some fundamental evolutionary questions, they are essentially misleading about many others.
659 citations
TL;DR: The proposed methodology may allow the upgrading of an existing evaluation to incorporate the genomic information when the information attributable to genomics can be expressed as modifications to the numerator relationship matrix.
475 citations
References
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TL;DR: It is demonstrated that in the mouse, leptin is not a critical molecule for implantation, gestation, fetal growth and parturition but that the leptin resistance effect at mid-gestation aims to stimulate food intake thus providing sustained energy resources for pregnancy.
Abstract: Leptin levels are significantly elevated in pregnant mice, rats and humans suggesting a critical role for leptin during gestation. To address whether leptin plays a putative role in the physiology of pregnancy, we asked whether a mouse pregnancy would be affected by the complete absence of leptin from both the mother and fetuses. Thus, leptin-deficient ob/ob females were first treated with exogenous leptin and then mated to similarly treated ob/ob males. All resulting fetuses have an ob/ob genotype and lack like their mothers any endogenous leptin production. Withdrawal of leptin treatment at 0.5, 6.5, 10.5 and 19.5 days p.c. did not affect any stage of the pregnancy despite a gradual return of the mothers to an obese state. However, some mice had delayed gestation periods of 21-23 days which were associated with prolonged parturition. The pups were normally delivered with no obvious signs of deformities although none survived beyond a day after delivery due to failure of lactation. Monitoring daily food intake of pregnant ob/ob females treated throughout gestation with leptin revealed significantly elevated levels of food intake from day 10 p.c. and onward demonstrating an attenuation of a leptin response during pregnancy and a leptin resistance effect. These studies demonstrate that in the mouse, leptin is not a critical molecule for implantation, gestation, fetal growth and parturition but that the leptin resistance effect at mid-gestation aims to stimulate food intake thus providing sustained energy resources for pregnancy.
148 citations
TL;DR: The proposed method to calculate gene content using a linear regression has similar capability to predict gene content as the iterative peeling method, however it requires less time and can be more practical for large pedigrees.
Abstract: Gene content is the number of copies of a particular allele in a genotype of an animal. Gene content can be used to study additive gene action of candidate gene. Usually genotype data are available only for a part of population and for the rest gene contents have to be calculated based on typed relatives. Methods to calculate expected gene content for animals on large complex pedigrees are relatively complex. In this paper we proposed a practical method to calculate gene content using a linear regression. The method does not estimate genotype probabilities but these can be approximated from gene content assuming Hardy-Weinberg proportions. The approach was compared with other methods on multiple simulated data sets for real bovine pedigrees of 1 082 and 907 903 animals. Different allelic frequencies (0.4 and 0.2) and proportions of the missing genotypes (90, 70, and 50%) were considered in simulation. The simulation showed that the proposed method has similar capability to predict gene content as the iterative peeling method, however it requires less time and can be more practical for large pedigrees. The method was also applied to real data on the bovine myostatin locus on a large dual-purpose Belgian Blue pedigree of 235 133 animals. It was demonstrated that the proposed method can be easily adapted for particular pedigrees.
147 citations
TL;DR: A regulatory role for CD37 is demonstrated in T cell proliferation by influencing early events of TCR signaling by crossing-linking on human T cells transduced signals that led to complete inhibition of CD3-induced proliferation.
Abstract: CD37 is a leukocyte-specific protein belonging to the tetraspanin superfamily. Previously thought to be predominantly a B cell molecule, CD37 is shown in this study to regulate T cell proliferation. CD37-deficient (CD37(-/-)) T cells were notably hyperproliferative in MLR, in response to Con A, or CD3-TCR engagement particularly in the absence of CD28 costimulation. Hyperproliferation was not due to differences in memory to naive T cell ratios in CD37(-/-) mice, apoptosis, or TCR down-modulation. Division cycle analyses revealed CD37(-/-) T cells to enter first division earlier than wild-type T cells. Importantly, proliferation of CD37(-/-) T cells was preceded by enhanced early IL-2 production. We hypothesized CD37 to be involved in TCR signaling and this was supported by the observation that CD4/CD8-associated p56(Lck) kinase activity was increased in CD37(-/-) T cells. Remarkably, CD37 cross-linking on human T cells transduced signals that led to complete inhibition of CD3-induced proliferation. In the presence of CD28 costimulation, CD37 engagement still significantly reduced proliferation. Taken together, these results demonstrate a regulatory role for CD37 in T cell proliferation by influencing early events of TCR signaling.
135 citations
TL;DR: A direct test for determining the presence of the recessive allele causing red coat color in black Holstein cattle was attempted, assuming that the molecular basis of the bovine coat color phenotypes determined at the extension locus was similar to the one in horses and mice.
Abstract: In mammals, red/yellow and brown/black colorations are determined by the distribution of two pigments, phaeomelanin and eumelanin, respectively, the relative amounts of which are controlled primarily by two loci, extension and agouti. Dominant alleles at the extension locus increase brown/black pigmentation, while recessive alleles block eumelanin synthesis, thereby extending red/ yellow pigmentation within the hair follicle melanocyte. Robbins and associates (1993) have shown that the pigmentation phenotypes in mice controlled by the extension locus result from point mutations altering the function of the melanocyte-stimulating hormone receptor (MSHR). Johannson and colleagues (1994) demonstrated cosegregation of the chestnut (red) coat color in horses and polymorphisms at the MSHR locus. The black and red coat colors, respectively, in cattle are also controlled at the extension locus, the red color being due to a recessive allele (Searle 1968). The Holstein breed is stratified in red and black subpopulations. Gene flow from the black and white to the red and white subpopulation is through rare black carriers of the recessive red allele. To develop a direct test for determining the presence of the recessive allele causing red coat color in black Holstein cattle, we attempted to PCR amplify the bovine MSHR gene, assuming that the molecular basis of the bovine coat color phenotypes determined at the extension locus was similar to the one in horses and mice. The human (Chhajlani and Wikberg 1992) and mouse (Mountjoy et al. 1992) MSHR sequences were aligned to identify highly homologous regions suitable for designing primers based on the human sequences. In a first attempt we tried to amplify bovine DNA corresponding to a 544-bp segment of the human sequence using primer 1 and primer 2 (see Table 1). PCR was carried out in a reaction volume of 25 Ixl containing 100 ng of bovine or human genomic DNA, 10 mM Tris-HC1 pH 8.9, 50 mM KC1, 200 ~M of each deoxynucleotide, 0.4 ~M of each primer, and 2.5 U of Taq DNA polymerase (Boehringer Mannheim, Germany) in a thermal cycles (Hybaid Teddington, UK). MgC12 concentrations ranging from 1.5 to 3.0 mM with 0.5-mM increments were tested to optimize the PCR for specific amplification. After initial denaturation for 5 min at 95~ the PCR profile consisted of a denaturation step at 94~ for 30 s, an annealing step at 62~ for 30 s, and an elongation step at 72~ for 30 s for a total of 30 cycles, followed by a final extension of 7 min at 72~ The PCR product obtained when using bovine template DNA of a black Holstein animal consisted of two major bands between 500 and 600 bp, that is in the range of the human band at 544 bp. The two bovine bands were recovered from the agarose gel according to Heery and coworkers (1990) and subjected individually to another round of
135 citations
Journal Article•
TL;DR: Several options are available for including genomic relationships in genetic evaluations, and each may be a valid answer to the question “Are two individuals related?"
Abstract: Models that include genomic relationships can predict genetic effects more accurately than those that use expected relationships from pedigrees. Relationship matrices can estimate the expected fraction of genes identical by descent, the actual fraction of DNA shared, or the fraction of alleles shared for loci that affect a particular trait. Each may be a valid answer to the question “Are two individuals related?” Several options are available for including genomic relationships in genetic evaluations.
129 citations