Quantitative trait loci for growth traits in C57BL/6J × DBA/2J mice

Quantitative trait loci (QTLs) for body weight and tail length are mapped in an F₂ population of 927 C57BL/6J × DBA/2J mice. We test the concordance between the locations of the mapped QTLs with those detected by changes of marker frequency under artificial selection in a previous experiment with the same base population. The directions of effects of the QTLs are generally in agreement, and in many cases significant QTLs are found in similar map positions, but there are also discrepancies between the two experiments. There are indications of age-specific QTL effects on growth. For body weight traits, the genetic variation in the F₂ appears to result from many loci with relatively small effects. For tail length at 10 weeks, however, a single QTL on Chromosome (Chr) 1 with a peak LOD score of ∼33 contributes most of the genetic variation detected, changes the trait value by about 6%, and explains about 20% of the phenotypic variance of the trait. Received: 4 August 1998 / Accepted: 17 November 1998     

What do mice select for in seeds?

Summary Knowledge of the basis upon which granivores select seeds is crucial to the understanding of granivory. In this study the preferences of three rodent granivores among seeds of 11 plants from the semi-arid Karoo of South Africa were estimated, and related to the physical and chemical attributes of the seeds. Seed weights and calorific, moisture, protein, polyphenol, ash, lipid and silica contents were estimated and cell contents, soluble ash and soluble carbohydrate contents were derived from these values. These attributes were determined for both the intact seeds and the portion of the seed that is ingested by the mice. The efficiency with which mice ingested the seeds (in terms of time and mass) was recorded. All three mouse species ranked the seeds similarly, and the two species for which handling efficiency was measured did not differ in this regard. Preference hierachies were highly correlated with the rate of energy intake, as predicted by optimal foraging theory. There was no correlation between rodent preferences and the gross energy content of the seeds, emphasising the importance of measuring relevant parameters. The energy yield of the seeds calculated here, in conjunction with rodent population energy requirements and dietary data, may be used to estimate potential granivore impact on the seed production of the plant community.     

Haemoglobin synthesis in 28 obligatory cases for α-thalassemia traits

Summary In the Far East two types of -thalassemia genes, namely -thalassemia₁ (-thal₁) and -thalassemia₂ (-thal₂) exist. Definite diagnosis of the -thal₁ and -thal₂ traits is very difficult because their hematological findings are minimally abnormal or normal. This study attempts to characterize the heterozygotes by hemoglobin chain synthesis in reticulocytes from obligatory cases of the -thal₁ and -thal₂ traits. Twelve parents of babies with hemoglobin Bart's hydrops fetalis (obligatory -thal₁ trait) had the mean total radioactivity / ratio of 0.76±SD 0.04, while that of 7 normal controls was 1.06±SD 0.04. The / globin chain ratios of 16 cases, who were either parents or offspring of patients with hemoglobin H disease, were found to segregate into 2 groups, i.e. 0.78±SD 0.03 (10 cases) and 0.92±SD 0.03 (6 cases), probably representing the -thal₁ and -thal₂ traits respectively. The hematological data of the first group showed definite hypochromic microcytic red cells, similar to thoseof the parents of the hydrops. The second group had significantly higher mean corpuscular hemoglobin than the first group, compatible with -thal₂ trait. Our globin chain synthesis study thus appears to be capable of discriminating normal, -thal₁ and -thal₂ traits.A preliminary report of the results was presented at the XV Congress of the International Society of Haematology, Israel, September, 1974.     

Cyclic variation in women’s preferences for masculine traits

Women’s preferences for several male traits, including voices, change over the menstrual cycle, but the proximate causes of these changes are unknown. This paper explores relationships between levels of estradiol, progesterone, luteinizing hormone, follicle stimulating hormone, prolactin, and testosterone (estimated using menstrual cycle information) and women’s preferences for male vocal masculinity in normally cycling and hormonally contracepting heterosexual females. Preferences for vocal masculinity decreased with predicted progesterone levels and increased with predicted prolactin levels in normally cycling—but not hormonally contracepting—women. Adaptive explanations for menstrual variation in women’s preferences for masculine traits are discussed and evaluated in light of these findings.     

Detecting QTL for feed intake traits and other performance traits in growing pigs in a Piétrain-Large White backcross

Knowing the large difference in daily feed intake (DFI) between Large White (LW) and Piétrain (PI) growing pigs, a backcross (BC) population has been set up to map QTL that could be used in marker assisted selection strategies. LW × PI boars were mated with sows from two LW lines to produce 16 sire families. A total of 717 BC progeny were fed ad libitum from 30 to 108 kg BW using single-place electronic feeders. A genome scan was conducted using genotypes for the halothane gene and 118 microsatellite markers spread on the 18 porcine autosomes. Interval mapping analyses were carried out, assuming different QTL alleles between sire families to account for within breed variability using the QTLMap software. The effects of the halothane genotype and of the dam line on the QTL effect estimates were tested. One QTL for DFI (P < 0.05 at the chromosome-wide (CW) level) and one QTL for feed conversion ratio (P < 0.01 at the CW level) were mapped to chromosomes SSC6 - probably due to the halothane alleles - and SSC7, respectively. Three putative QTL for feed intake traits were detected (P < 0.06 at the CW level) on SSC2, SSC7 and SSC9. QTL on feeding traits had effects in the range of 0.20 phenotypic s.d. The relatively low number of QTL detected for these traits suggests a large QTL allele variability within breeds and/or low effects of individual loci. Significant QTL were detected for traits related to carcass composition on chromosomes SSC6, SSC15 and SSC17, and to meat quality on chromosome SSC6 (P < 0.01 at the genome-wide level). QTL effects for body composition on SSC13 and SSC17 differed according to the LW dam line, which confirmed that QTL alleles were segregating in the LW breed. An epistatic effect involving the halothane locus and a QTL for loin weight on SSC7 was identified, the estimated substitution effects for the QTL differing by 200 g between Nn and NN individuals. The interactions between QTL alleles and genetic background or particular genes suggest further work to validate QTL segregations in the populations where marker assisted selection for the QTL would be applied.     

Dissection of complex traits in forest trees — opportunities for marker-assisted selection

Due to their long reproductive cycles and the time to expression of mature traits, marker-assisted selection is particularly attractive for tree breeding. In this review, we discuss different approaches used for developing markers and propose a method for application of markers in low linkage disequilibrium (LD) populations. Identification of useful markers for application in tree breeding is mainly based on two approaches, quantitative trait locus (QTL) mapping and association genetic studies. While several studies have identified significant markers, effect of the individual markers is low making it difficult to utilize them in breeding programs. Recently, genomic selection (GS) was proposed for overcoming some of these difficulties. In GS, high density markers are used for predicting phenotypes from genotypes. Currently small effective populations with high LD are being tested for GS in tree breeding. For wider application, GS needs to be applied in low LD populations which are found in many tree breeding programs. Here we propose an approach in which the significant markers from association studies may be used for developing prediction models in low LD populations using the same methods as in GS. Preliminary analyses indicate that a modest numbers of markers may be sufficient for developing prediction models in low LD populations. GS based on large numbers of random markers or small numbers of associated markers is poised to make marker-assisted selection a reality in forest tree breeding.     

Identification of the heterozygous state for the α1-antitrypsin deficiency gene in man

Alpha₁-antitrypsin (₁-at) of individuals homozygous for a gene determining low serum concentrations of this protein can be distinguished electrophoretically from ₁-at of homozygotes for the more common gene. Heterozygotes possess both electrophoretic species, and they may have ₁-at levels intermediate between those of both homozygotes or may be in the range of the homozygotes for the common gene. The frequency of the gene determining a deficiency of ₁-at in a population sample of 100 individuals was 0.075.This work was supported in part by NIH Program Project Grant HE-06285 from the National Heart Institute.     

Susceptibility gene search for nephropathy and related traits in Mexican–Americans

The rising global epidemic of diabetic nephropathy (DN) will likely lead to increase in the prevalence of cardiovascular morbidity and mortality posing a serious burden for public health care. Despite greater understanding of the etiology of diabetes and the development of novel treatment strategies to control blood glucose levels, the prevalence and incidence rate of DN is increasing especially in minority populations including Mexican–Americans. Mexican–Americans with type 2 diabetes (T2DM) are three times more likely to develop microalbuminuria, and four times more likely to develop clinical proteinuria compared to non-Hispanic whites. Furthermore, Mexican–Americans have a sixfold increased risk of developing renal failure secondary to T2DM compared to Caucasians. Prevention and better treatment of DN should be a high priority for both health-care organizations and society at large. Pathogenesis of DN is multi-factorial. Familial clustering of DN-related traits in MAs show that DN and related traits are heritable and that genes play a susceptibility role. While, there has been some progress in identifying genes which when mutated influence an individual’s risk, major gene(s) responsible for DN are yet to be identified. Knowledge of the genetic causes of DN is essential for elucidation of its mechanisms, and for adequate classification, prognosis, and treatment. Self-identification and collaboration among researchers with suitable genomic and clinical data for meta-analyses in Mexican–Americans is critical for progress in replicating/identifying DN risk genes in this population. This paper reviews the approaches and recent efforts made to identify genetic variants contributing to risk for DN and related phenotypes in the Mexican–American population.     

Why are rare traits unilaterally expressed?: Trait frequency and unilateral expression for cranial nonmetric traits in humans

Based on an analysis of nonmetric trait databases from several large skeletal series in Northern Europe and South America, representing 27 bilateral traits, we report a predictable relationship between the frequency of nonmetric traits and the probability that they are expressed bilaterally. In a wider sampling of traits and populations, this study thus confirms the findings of an earlier study by Ossenberg ([1981] Am. J. Phys. Anthropol. 54:471-479), which reported the same relationship for two mandibular traits. This trend was previously explained by extending the multifactorial threshold model for discontinuous traits to incorporate either separate thresholds for unilateral or bilateral expression, or by a fuzzy threshold in which the probability of bilateral expression increases away from the median threshold value. We show that the trend is produced under the standard multifactorial threshold model for discontinuous traits simply if the within-individual or developmental instability variance remains relatively constant across the range of liability. Under this assumption, the number of individuals in which one side but not the other is pushed over the threshold for trait formation will be a larger proportion of the number of individuals expressing the trait when the trait frequency is low. As trait frequency increases, the significance of within-individual variance as a determinant of trait formation decreases relative to the genetic and among-individual environmental variance. These results have implications for interpreting nonmetric trait data as well as for understanding the prevalence of unilateral vs. bilateral expression of a wide variety of discontinuous traits, including dysmorphologies in humans.     

Count Bayesian models for genetic analysis of in vitro embryo production traits in Guzerá cattle

Four models for in vitro embryo production traits in Guzerá cattle were compared: Gaussian (untransformed variable – LIN and transformed in logarithmic scale – LOG), Poisson (POI) and zero-inflated Poisson (ZIP). Data consisted of 5716 ovum pick-up and in vitro fertilization records performed in 1205 cows from distinct regions of Brazil. Analyzed count traits were the number of viable oocytes (N_OV), number of grade I oocytes (N_GI), number of degenerated oocytes (N_DG), number of cleaved embryos (N_CLV) and number of viable produced embryos (N_EMB). Heritability varied from 0.17 (LIN) to 0.25 (POI) for N_OV; 0.08 (LOG) to 0.18 (ZIP) for N_GI; 0.12 (LIN) to 0.20 (POI) for N_DG; 0.13 (LIN) to 0.19 (POI) for N_CLV; 0.10 (LIN) to 0.20 (POI) for N_EMB depending on the considered model. The estimated repeatability varied from 0.53 (LOG) to 0.63 (POI) for N_OV; 0.22 (LOG) to 0.39 (ZIP) for N_GI; 0.29 (LIN) to 0.42 (ZIP) for N_DG; 0.42 (LIN) to 0.59 (POI) for N_CLV; 0.36 (LIN) to 0.51 (POI) for N_EMB. The goodness of fit, measured by deviance information criterion and mean squared residuals, suggested superiority of POI and ZIP over Gaussian models. Estimated breeding values (EBV) obtained by different models were highly correlated, varying from 0.92 for N_OV (between LIN-POI) and 0.99 for N_GI (between POI-ZIP). The number of coincident animals on the 10% top EBV showed lower similarities. We recommend POI and ZIP models as the most adequate for genetic analysis of in vitro embryo production traits in Guzerá cattle.     

Impaired bone formation and osteopenia in heterozygous β<Superscript>IVSII-654</Superscript> knockin thalassemic mice

β-thalassemia caused by the C→T mutation at nucleotide 654 of the intron 2 (β^IVSII-654) results in aberrant splicing of β-globin RNA, leading to an almost absence of β-globin synthesis. Although trabecular and cortical bone loss was previously reported in β-thalassemic mice with deletion of β-globin gene, the microscopic changes in trabecular structure in β^IVSII-654 thalassemic mice remained elusive. Here, we investigated the macroscopic and microscopic bone changes in 12-week-old β^IVSII-654 knockin thalassemic mice by dual-energy X-ray absorptiometry (DXA) and histomorphometric analysis, respectively. DXA revealed a decrease in bone mineral density in the lumbar vertebrae and tibial metaphysis, but not in the femoral diaphysis, suggesting that β^IVSII-654 thalassemia predominantly led to osteopenia at the trabecular site, but not the cortical site. Further histomorphometric analysis of the tibial secondary spongiosa showed that trabecular bone volume was significantly decreased with the expansion of marrow cavity. Decreases in osteoblast surface, osteoid surface, mineral apposition rate, mineralizing surface, and mineralized volume were also observed. Moreover, trabecular bone resorption was markedly enhanced as indicated by increases in the osteoclast surface and eroded surface. It could be concluded that β^IVSII-654 thalassemia impaired bone formation and enhanced bone resorption, thereby leading to osteopenia especially at the trabecular sites, such as the tibial metaphysis.     

Interfamily variation in amphibian early life-history traits: raw material for natural selection?

The embryonic development and time to hatching of eggs can be highly adaptive in some species, and thus under selective pressure. In this study, we examined the underlying interfamily variation in hatching timing and embryonic development in a population of an oviparous amphibian, the rough-skinned newt (Taricha granulosa). We found significant, high variability in degree of embryonic development and hatching timing among eggs from different females. Patterns of variation were present regardless of temperature. We also could not explain the differences among families by morphological traits of the females or their eggs. This study suggests that the variation necessary for natural selection to act upon is present in the early life history of this amphibian.     

Is seasonal variation in leaf traits adaptive for the annual plant Dicerandra linearifolia?

Empirical studies of phenotypic plasticity have often relied on the plausibility that a plastic response to the environment would increase fitness in order to diagnose the response as adaptive. I conducted a test of the hypothesis that seasonal variation in leaf traits is an adaptive response to seasonal variation in environmental conditions faced by the annual plant Dicerandralinearifolia. This species exhibits variation in leaf morphology and anatomy in response to temperature that is consistent with the expectations for adaptive plasticity. I examined variation in the size, thickness and density of stomata of leaves that develop in summer and winter and used analysis of phenotypic selection during winter and summer seasons to test the hypothesis that seasonal variation in these traits is adaptive. Regression analyses of estimated dry mass (as a proxy for fitness) on leaf traits revealed no evidence supporting the adaptive hypothesis. Selection favoured individuals with large and thick leaves in both winter and summer, and density of stomata had little or no effect on estimated relative fitness in any season. Correspondence between seasonal variation in leaf thickness and density of stomata and expectations for adaptive plasticity appears to be purely fortuitous. Seasonal variation in leaf traits may persist simply because there is no selection against individuals in which these traits vary. My results underscore the importance of definitive tests of the hypothesis of adaptation to distinguish adaptive plasticity from neutral or nonadaptive phenotypic plasticity.     

Improved in situ β-galactosidase staining for histological analysis of transgenic mice

The present study describes a novel method for the histochemical demonstration of -galactosidase activity on tissue sections. We have replaced 5-bromo-4-chloro-3-indolyl--D-galactoside (X-Gal) with 5-bromoindolyl--o-galactopyranoside (Bluo-Gal) as a chromogenic substrate for the bacterial -galactosidase (lacZ). After -galactosidic cleavage, Bluo-Gal precipitates in form of fine birefringent crystals, whereas X-gal gives rise to an amorphous precipitate. Upon microscopic examination under polarized light, the crystals emit a strong signal consisting of yellow reflected light. This property of Bluo-Gal results in greatly enhanced sensitivity of the staining method for -galactosidase and allows for optimal morphological resolution. To exemplify the applications of this technique, the expression is demonstrated in transgenic mice of -galactosidase driven by a fragment of the human tissue-type plasminogen activator promoter.     

Genomic selection for fruit quality traits in apple (Malus×domestica Borkh.)

The genome sequence of apple (Malus×domestica Borkh.) was published more than a year ago, which helped develop an 8K SNP chip to assist in implementing genomic selection (GS). In apple breeding programmes, GS can be used to obtain genomic breeding values (GEBV) for choosing next-generation parents or selections for further testing as potential commercial cultivars at a very early stage. Thus GS has the potential to accelerate breeding efficiency significantly because of decreased generation interval or increased selection intensity. We evaluated the accuracy of GS in a population of 1120 seedlings generated from a factorial mating design of four females and two male parents. All seedlings were genotyped using an Illumina Infinium chip comprising 8,000 single nucleotide polymorphisms (SNPs), and were phenotyped for various fruit quality traits. Random-regression best liner unbiased prediction (RR-BLUP) and the Bayesian LASSO method were used to obtain GEBV, and compared using a cross-validation approach for their accuracy to predict unobserved BLUP-BV. Accuracies were very similar for both methods, varying from 0.70 to 0.90 for various fruit quality traits. The selection response per unit time using GS compared with the traditional BLUP-based selection were very high (>100%) especially for low-heritability traits. Genome-wide average estimated linkage disequilibrium (LD) between adjacent SNPs was 0.32, with a relatively slow decay of LD in the long range (r(2)?=?0.33 and 0.19 at 100 kb and 1,000 kb respectively), contributing to the higher accuracy of GS. Distribution of estimated SNP effects revealed involvement of large effect genes with likely pleiotropic effects. These results demonstrated that genomic selection is a credible alternative to conventional selection for fruit quality traits.     

Integrin β1 is required for maintenance of vascular tone in postnatal mice

Connective tissue is required for maintaining the integrity of tissues. Integrins are the cell surface receptors responsible for cell attachment to extracellular matrix; however, their tissue-specific role in this process is poorly understood. Here, we test whether integrin β1 is required for blood vessel maintenance and integrity in adult mice. We show that adult mice containing a fibroblast/smooth muscle cell-specific deletion of integrin β1 exhibit impaired bleeding time and maintenance of vessel architecture, including progressively reduced levels of extracellular matrix (ECM). Vessels also possessed diminished levels of α-smooth muscle actin (α-SMA), and cells derived from vessels showed reduced production of mRNAs encoding ECM and α-SMA as well as reduced α-SMA protein and stress fibers and ECM contraction. Integrin β1 in adult fibroblasts/smooth muscle cells/pericytes is required for vasoconstriction and vascular maintenance.     

Little and often? Maintaining continued performance in an automated T-maze for mice

Operant and maze tasks in mice are limited by the small number of trials possible in a session before mice lose motivation. We hypothesized that by manipulating reward size and session length, motivation, and hence performance, would be maintained in an automated T-maze. We predicted that larger rewards and shorter sessions would improve acquisition; and smaller rewards and shorter sessions would maintain higher and less variable performance. Eighteen C57BL/6J mice (9 per sex) acquired (criterion 8/10 correct) and performed a spatial discrimination, with one of 3 reward sizes (.02, .04, or .08 g) and one of 3 session schedules (15, 30, or 45 min sessions). Each mouse had a total of 360 min of access to the maze per night, for two nights, and averaged 190 trials. Analysis used split-plot GLM with contrasts testing for linear effects. Acquisition of the discrimination was unaffected by reward size or session length/interval. After-criterion average performance improved as reward size decreased. After-criterion variability in performance was also affected. Variability increased as reward size increased. Session length/interval did not affect any outcome. We conclude that an automated maze, with suitable reward sizes, can sustain performance with low variability, at 5-10 times faster than traditional methods.