Generalized marker regression and interval QTL mapping methods for binary traits in half-sib family designs

A Generalized Marker Regression Mapping (GMR) approach was developed for mapping Quantitative Trait Loci (QTL) affecting binary polygenic traits in a single-family half-sib design. The GMR is based on threshold-liability model theory and regression of offspring phenotype on expected marker genotypes at flanking marker loci. Using simulation, statistical power and bias of QTL mapping for binary traits by GMR was compared with full QTL interval mapping based on a threshold model (GIM) and with a linear marker regression mapping method (LMR). Empirical significance threshold values, power and estimates of QTL location and effect were identical for GIM and GMR when QTL mapping was restricted to within the marker interval. These results show that the theory of the marker regression method for QTL mapping is also applicable to binary traits and possibly for traits with other non-normal distributions. The linear and threshold models based on marker regression (LMR and GMR) also resulted in similar estimates and power for large progeny group sizes, indicating that LMR can be used for binary data for balanced designs with large families, as this method is computationally simpler than GMR. GMR may have a greater potential than LMR for QTL mapping for binary traits in complex situations such as QTL mapping with complex pedigrees, random models and models with interactions.     

Use of a laryngeal mask airway in rabbits during isoflurane anesthesia

The purpose of this study was to find out if an LMA (#1 LMA‐Classic) would provide a better airway than a face mask in spontaneously breathing anesthetized rabbits, and to test if it could be used for mechanically controlled ventilation. Sixteen rabbits (4.1 ± 0.8 kg, mean ± SD) were assigned randomly to three treatment groups; face mask with spontaneous ventilation (FM‐SV; n = 5), LMA with spontaneous ventilation (LMA‐SV; n = 5), and LMA with controlled ventilation (LMA‐CV; n = 6). Rabbits were anesthetized in dorsal recumbency using a circle circuit at constant ET isoflurane (2.3%, Datex airway gas monitor) and constant rectal temperature (38.85 °C) for 2 hours. PaCO₂, PaO₂, minute volume, tidal volume (Wright's respirometer), and Pe CO₂ were measured at 15 minute intervals. Two individuals in the FM‐SV group had PaCO₂ >100 mm Hg (>13.3 kPa). One rabbit in the FM‐SV had PaO₂ <80 mm Hg (<10.7 kPa). All FM‐SV rabbits showed signs of airway obstruction and two were withdrawn from the study at 45 and 90 minutes, respectively, because of cyanosis. Tidal volume could not be measured in the FM‐SV group. No signs of airway obstructions were observed in either of the LMA groups. Four rabbits in the LMA‐CV group developed gastric tympany, and one of these refluxed after 110 minutes. The significance of differences between the two spontaneously breathing groups and between the two LMA groups were measured using Wilcoxon's rank sum test (with significance assumed at p < 0.05). There were no statistical differences between FM‐SV and LMA‐SV in any variable tested. PaCO₂ and Pe ′CO₂ were less in the LMA‐CV group than in the LMA‐SV group, while PaO₂, tidal volume, and minute volume were all more. We conclude that biologically, the LMA provides a better airway than the face mask during spontaneous breathing and that it can be used for IPPV, but that gastric tympany is likely to occur during IPPV.     

Morphological characteristics of blood cells in monitor lizards: is erythrocyte size linked to actual body size?

Blood cell morphology and count are not uniform across species. Recently, between‐species comparisons revealed that the size of red blood cells is associated with body size in some lizard taxa, and this finding was interpreted in the context of the metabolic theory. In the present study, we examined the numbers and the size of blood cells in 2 species of monitor lizards, the mangrove‐dwelling monitor (Varanus indicus) and the savannah monitor (V. exanthematicus), and we compared these traits in individuals of different body size. The results revealed that during the course of ontogeny, the size of red blood cells increases with body mass. Because the mass‐specific metabolic rate decreases with body size and the cell volume‐to‐surface ratio decreases with the cell size, changes in the erythrocyte size might be the result of oxygen transport adjustment.     

Revival of a well-known, but ignored correction term for χ2 in linkage analysis with small samples

The ‘classical’χ² test is routinely applied in linkage analysis. The values customarily used, however, are only approximations since continuous χ² terms are used instead of discrete multinomial terms. This error becomes increasingly important as the sample becomes small. In this note, a well-known correction term for improvement of this approximation is revived and numerically calculated for some interesting cases from linkage studies.     

Climate change record in subsurface temperatures: A global perspective

Analyses of underground temperature measurements from 358 boreholes in eastern North America, central Europe, southern Africa, and Australia indicate that, in the 20th century, the average surface temperature of Earth has increased by about 0.5 degreesC and that the 20th century has been the warmest of the past five centuries. The subsurface temperatures also indicate that Earth's mean surface temperature has increased by about 1.0 degreesC over the past five centuries. The geothermal data offer an independent confirmation of the unusual character of 20th-century climate that has emerged from recent multiproxy studies.     

Selection on multiple QTL with control of gene diversity and inbreeding for long-term benefit

The purpose of this study was to develop and investigate selection strategies that aim at maximizing long-term genetic response while conserving gene diversity and controlling inbreeding in populations of limited effective size, assuming complete knowledge of all genes affecting a quantitative trait. Three selection strategies were proposed to select on 100 quantitative trait loci (QTL) and compared with truncation selection on breeding value. Alternative selection strategies aimed at maximizing the average breeding value of parents with a penalty on (1) the number of unfavourable QTL genotypes among parents (OS-I), (2) the negative of the logarithm of the frequency of the favourable allele at each QTL among parents (OS-II), and (3) the average pedigree relationship among parents (OS-III). When all QTL and their effects were known, the strategies examined were able to obtain extra long-term responses, conserve QTL diversity and reduce inbreeding, compared with truncation selection. Strategy OS-II was the most effective in conserving QTL diversity and OS-III in reducing inbreeding. By changing the magnitude of the penalties applied, the impact on long-term response, inbreeding and diversity can be controlled. Extra long-term responses over truncation selection of OS-I and OS-II were even greater when effects of QTL were estimated rather than assumed known, indicating the applicability of results to practical strategies for marker-assisted selection. Extra responses are expected to be reduced for larger population sizes.     

Effect of adenosine infusion on isoflurane MAC in dogs.

Adenosine is a potent analgesic in people and reduces the MAC of halothane in dogs. The purpose of this study was to determine whether adenosine reduces the MAC of isoflurane in dogs. Seven beagles (four males and three females) were anesthetized and randomly assigned to receive adenosine (0.3 mg kg^–1 minute^–1; 6 mL kg^–1 hour^–1, IV) or saline (0.9%, 6 mL kg^–1 hour^–1IV). After an interval of ≥7 days, each dog was reanesthetized and treated with the alternate infusion. Anesthesia was induced and maintained with isoflurane in oxygen. Dogs were intubated and instrumented for measurement of mean systemic arterial blood pressure and airway concentration of isoflurane and end‐tidal partial pressure of carbon dioxide. The MAC for isoflurane was determined using the tail‐clamp technique. Baseline MAC values were 1.25 (1.15, 1.35)% [median (minimum, maximum)] and 1.25 (1.05, 1.45)% before the saline and adenosine treatments, respectively. After 2 hours of infusion with saline or adenosine, MAC values were not different (p = 0.156) and were 1.25 (0.95, 1.35)% and 1.05 (1.00, 1.25)%, respectively. Two hours following the end of each infusion, the MAC values for saline and adenosine treatment groups differed significantly (p = 0.015), but by no more than the normal variation inherent in this study, and were 1.15 (1.15, 1.35)% and 1.05 (1.05, 1.25)%, respectively. Mean arterial blood pressure was 93 (74, 123) mm Hg for saline treated dogs and 67 (52, 72) mm Hg (p = 0.008) during adenosine infusion. End‐tidal carbon dioxide was not different between the two treatment groups. We conclude that adenosine administered at 0.3 mg kg^–1 minute^–1had no effect on isoflurane MAC in dogs, but decreased mean arterial blood pressure.     

Genetic correlations between body condition scores and fertility in dairy cattle using bivariate random regression models

Genetic correlations between body condition score (BCS) and fertility traits in dairy cattle were estimated using bivariate random regression models. BCS was recorded by the Swiss Holstein Association on 22,075 lactating heifers (primiparous cows) from 856 sires. Fertility data during first lactation were extracted for 40,736 cows. The fertility traits were days to first service (DFS), days between first and last insemination (DFLI), calving interval (CI), number of services per conception (NSPC) and conception rate to first insemination (CRFI). A bivariate model was used to estimate genetic correlations between BCS as a longitudinal trait by random regression components, and daughter's fertility at the sire level as a single lactation measurement. Heritability of BCS was 0.17, and heritabilities for fertility traits were low (0.01-0.08). Genetic correlations between BCS and fertility over the lactation varied from: -0.45 to -0.14 for DFS; -0.75 to 0.03 for DFLI; from -0.59 to -0.02 for CI; from -0.47 to 0.33 for NSPC and from 0.08 to 0.82 for CRFI. These results show (genetic) interactions between fat reserves and reproduction along the lactation trajectory of modern dairy cows, which can be useful in genetic selection as well as in management. Maximum genetic gain in fertility from indirect selection on BCS should be based on measurements taken in mid lactation when the genetic variance for BCS is largest, and the genetic correlations between BCS and fertility is strongest.     

RADIOGRAPHIC AND ULTRASONOGRAPHIC EVALUATION OF THE PATELLAR LIGAMENT FOLLOWING TIBIAL TUBEROSITY ADVANCEMENT

Effect of tibial tuberosity advancement (TTA) on the patellar ligament has not been described. Our purpose was to evaluate the patellar ligament radiographically and ultrasonographically before and after a TTA. Twenty‐one stifles (20 dogs) were evaluated preoperatively (T0), and at six (n=18) (T1) and 16 weeks (n=17) (T2) postTTA. Radiographically, proximal and distal thickness of the patellar ligament was assessed and a ratio to the total length of the ligament was calculated to compensate for the magnification. Ultrasound evaluation included measurements of the transverse thickness and cross‐sectional area at three different levels, as well as a subjective score of ligament changes. In comparison with T0, all radiographic and ultrasonographic measurements increased significantly, 6 weeks postoperatively (P≤0.04), and did not change 16 weeks postoperatively compared with T1. The subjective score worsened significantly from T0 to T1 and T0 to T2 (P<0.0001), and improved significantly from T1 to T2 (P=0.02). Larger cage size was associated with a more severe increase in radiographic proximal thickness to total length ratio and ultrasonographic middle transverse area at both follow‐up examinations (P0.02). Dogs in which arthrotomy was not performed appeared to have ultrasonographically less changes. In conclusion, patellar desmopathy was a common postoperative sequel to TTA. Surgical trauma, arthrotomy, perfusion injury, complete vs. partial cranial cruciate ligament rupture, larger tibial advancement, postoperative activity or altered insertion angle of the patellar ligament at the tibial tuberosity are suggested causes, that should be elucidated in a larger study cohort.     

EFFECT OF CONTRAST MEDIUM INJECTION DURATION ON PEAK ENHANCEMENT AND TIME TO PEAK ENHANCEMENT OF CANINE PULMONARY ARTERIES

Our goal was to investigate the effect of contrast medium injection duration on pulmonary artery peak enhancement and time to peak enhancement. Fourteen dogs were allocated into one of seven predefined weight categories, each category contained two dogs. Dogs in each weight category were assigned to group A or B. Animals in each group received a different contrast medium injection protocol. In group A, a fixed injection rate of 5 ml/s was used. In group B, the contrast injection rate was calculated as follows: flow rate=contrast volume/scan duration+10 s. Time to peak enhancement and peak enhancement of the main left and right pulmonary arteries were measured on single‐level, dynamic CT images for a fixed time of 30 s. Rank correlation (Spearman's) coefficients between injection duration and time to peak enhancement and between body weight and peak enhancement were calculated. For group A, there was a significant negative correlation between peak enhancement and weight (r=?0.94; P=0.005), while for group B, there was no significant correlation (r=?0.64 and P=0.18). There was a significant correlation between time to peak enhancement and injection duration in both groups (group A: r=0.99; P=0.006 and group B: r=0.85; P=0.02). In conclusion, injection duration is a key feature in a CT angiography injection protocol. A protocol with an injection duration adjusted to the scan duration seems to be particularly suitable for veterinary applications where a population with great weight variability is studied.