Approaches to interval mapping of QTL in a multigeneration pedigree: the example of porcine chromosome 4

Quantitative trait loci (QTLs) have been mapped in many studies of F2 populations derived from crosses between diverse lines. One approach to confirming these effects and improving the mapping resolution is genetic chromosome dissection through a backcrossing programme. Analysis by interval mapping of the data generated is likely to provide additional power and resolution compared with treating data marker by marker. However, interval mapping approaches for such a programme are not well developed, especially where the founder lines were outbred. We explore alternative approaches to analysis using, as an example, data from chromosome 4 in an intercross between wild boar and Large White pigs where QTLs have been previously identified. A least squares interval mapping procedure was used to study growth rate and carcass traits in a subsequent second backcross generation (BC2). This procedure requires the probability of inheriting a wild boar allele for each BC2 animal for locations throughout the chromosome. Two methods for obtaining these probabilities were compared: stochastic or deterministic. The two methods gave similar probabilities for inheriting wild boar alleles and, hence, gave very similar results from the QTL analysis. The deterministic approach has the advantage of being much faster to run but requires specialized software. A QTL for fatness and for growth were confirmed and, in addition, a QTL for piglet growth from weaning at 5 weeks up to 7 weeks of age and another for carcass length were detected.     

Testing for the presence of previously identified QTL for milk production traits in new populations

Five chromosomal regions previously associated with milk production traits were tested in 16 families of Black and White cattle from the UK. The traits were also linearly transformed into genetically and phenotypically independent variables normalized by phenotypic variances ('canonical traits'). Significant associations with the untransformed and canonical traits were found for bovine chromosome 6. There was also evidence that chromosome 9 influenced these traits. The linear transformation clarified the effects of chromosomal regions; regions with effects on all three untransformed traits (milk, fat and protein yields) were generally condensed into an effect on a single canonical trait. Comparison of our results with those reported previously for American Holstein cattle suggested that the QTL may not be the same.     

Candidate gene analysis of GH1 for effects on growth and carcass composition of cattle

We present an approach to evaluate the support for candidate genes as quantitative trait loci (QTLs) within the context of genome-wide map-based cloning strategies. To establish candidacy, a bacterial artificial chromosome (BAC) clone containing a putative candidate gene is physically assigned to an anchored linkage map to localise the gone relative to an identified QTL effect. Microsatellite loci derived from BAC clones containing an established candidate gone are integrated into the linkage map facilitating the evaluation by interval analysis of the statistical support for QTL identity. Permutation analysis is employed to determine experiment-wise statistical support. The approach is illustrated for the growth hormone 1 ( GH1 ) gene and growth and carcass phenotypes in cattle. Polymerase chain reaction (PCR) primers which amplify a 441 bp fragment of GH1 were used to systematically screen a bovine BAC library comprising 60 000 clones and with a 95% probability of containing a single copy sequence. The presence of GH1 in BAC-110R2C3 was confirmed by sequence analysis of the PCR product from this clone and by the physical assignment of BAC110R2C3 to bovine chromosome 19 (BTA19) band 22 by fluorescence in situ hybridisation (FISH). Microsatellite KHGH1 was isolated from BAC110R2C3 and scored in 529 reciprocal backcross and F₂ fullsib progeny from 41 resource families derived from Angus ( Bos taurus ) and Brahman ( Bos indicus ). The microsatellite KHGH1 was incorporated into a framework genetic map of BTA19 comprising 12 microsatellite loci, the erythrocyte antigen T and a GH1-TaqI restriction fragment length polymorphism (RFLP). Interval analysis localised effects of taurus vs. indicus alleles on subcutaneous fat and the percentage of ether extractable fat from the longissimus dorsi muscle to the region of BTA19 harbouring GH1 .     

Patterns of reproduction in Malayan silvered leaf monkeys at the Bronx Zoo

Within phylogenetic limits reproductive characteristics of a given species may vary between populations in response to ecological and social factors. For instance, in environments where high quality nutrition is readily available, the onset and speed of reproduction are often accelerated. Other influencing factors might be maternal experience or the sex of the infant. Here we present data on reproductive characteristics for the silvered leaf monkey (Trachypithecus cristatus), a medium‐sized Asian colobine housed at the Wildlife Conservation Society's Bronx Zoo as a one‐male group. To place the species into an appropriate phylogenetic context, we limited our comparison to other colobine species. Demographic data span 21.4 years (October 1985 to March 2007) and derive from 30 adult females (128.0 female years). Detailed behavioral data stem from a 2.2 years study (November 2002 to January 2005; 734 days, 4,225 hr). As in other Asian colobines, receptive periods were short (mean=4.3 days, n=68). This is expected for one‐male groups where receptivity likely indicates, rather than conceals, ovulation. Gestation length was estimated based on a change in the pattern of sexual behavior (mean=194.6 days, n=7). It fell within the range reported for the taxon. Births occurred year round, at an early age (mean=2.9 years, n=8), at short intervals (mean=14.9 months, n=59) in combination with a short lactation (mean 12.1 months, n=9) likely due to the nearly unlimited availability of nutrition in this zoo setting. Primiparous females tended to have a longer first interbirth interval but infant survival rates were similar to multipara possibly due to the absence of predators. Maternal investment was independent of the infant's sex and birth sex ratio was even. Our results emphasize that when interpreted with caution, zoo populations yield realistic reproductive characteristics that can help fill the gap in our knowledge about colobine life history. Am. J. Primatol. 71:852–859, 2009. © 2009 Wiley‐Liss, Inc.     

T波峰-末间期对急性心肌梗死并发室性心律失常的预测价值

目的:探讨T波峰-末间期(Tp-Te间期)和Tp-Te间期离散度(Tp-Ted)对急性心肌梗死并发室性心律失常的预测价值。方法:选择我院2013年5月至2014年5月收治的140例确诊急性ST段抬高型心肌梗死(STEMI)患者,按照心律失常类型分为室性心动过速组,室性早搏组以及无室性心律失常组。分析并比较各组患者心电图Tp-Te间期及Tp-Ted的变化情况。结果:急性期FPG、Tp-Te、Tp-Ted高于恢复期,差异有统计学意义(P0.05);急性期与恢复期之间TG、CHOL、LDL-C、K+、Na+水平差异无统计学意义(P0.05)。无室性心律失常组与室性心动过速组及室性早搏组比较,Tp-Te和Tp-Ted更低,差异有统计学意义(P0.05);室性早搏组和室性心动过速组比较,Tp-Te和Tp-Ted更低,差异有统计学意义(P0.05)。结论:Tp-Te间期和Tp-Ted可用于区分急性心肌梗死患者室性心律失常类型。     

Development of two forensically important blowfly species (Chrysomya megacephala and Chrysomya rufifacies) (Diptera: Calliphoridae) at four temperatures in India

The development of the Oriental latrine fly, Chrysomya megacephala (Fabricius), and hairy maggot blowfly, C. rufifacies (Macquart) (Diptera: Calliphoridae), was studied at four different temperatures (22°C, 25°C, 29°C and 31°C) in order to draw correlations between larval age, body length and body dry weight. The mean larval body length increased steadily from a minimum of 1.4 mm for C. megacephala and 1.8 mm for C. rufifacies to a maximum of 17.4 mm for C. megacephala and 15.9 mm for C. rufifacies at different temperatures. Similarly, the mean dry weight increased steadily from a minimum of 0.0007 g for C. megacephala (second instar) and 0.0008 g for C. rufifacies (second instar) to a maximum of 0.0290 g for C. megacephala and 0.0270 g for C. rufifacies at different temperatures. Entomological evidence is often used to estimate the minimum postmortem interval (mPMI) and both of these species are important from a forensic point of view. Graphs of age of larvae vs. body length and age of larvae vs. dry body weight at different temperatures can be used to estimate the larval age of these two species.     

A New Simple Method for Improving QTL Mapping Under Selective Genotyping

The selective genotyping approach, where only individuals from the high and low extremes of the trait distribution are selected for genotyping and the remaining individuals are not genotyped, has been known as a cost-saving strategy to reduce genotyping work and can still maintain nearly equivalent efficiency to complete genotyping in QTL mapping. We propose a novel and simple statistical method based on the normal mixture model for selective genotyping when both genotyped and ungenotyped individuals are fitted in the model for QTL analysis. Compared to the existing methods, the main feature of our model is that we first provide a simple way for obtaining the distribution of QTL genotypes for the ungenotyped individuals and then use it, rather than the population distribution of QTL genotypes as in the existing methods, to fit the ungenotyped individuals in model construction. Another feature is that the proposed method is developed on the basis of a multiple-QTL model and has a simple estimation procedure similar to that for complete genotyping. As a result, the proposed method has the ability to provide better QTL resolution, analyze QTL epistasis, and tackle multiple QTL problem under selective genotyping. In addition, a truncated normal mixture model based on a multiple-QTL model is developed when only the genotyped individuals are considered in the analysis, so that the two different types of models can be compared and investigated in selective genotyping. The issue in determining threshold values for selective genotyping in QTL mapping is also discussed. Simulation studies are performed to evaluate the proposed methods, compare the different models, and study the QTL mapping properties in selective genotyping. The results show that the proposed method can provide greater QTL detection power and facilitate QTL mapping for selective genotyping. Also, selective genotyping using larger genotyping proportions may provide roughly equivalent power to complete genotyping and that using smaller genotyping proportions has difficulties doing so. The R code of our proposed method is available on http://www.stat.sinica.edu.tw/chkao/.     

Some model based considerations on observing generation times for communicable diseases

The generation time of an infectious disease is usually defined as the time from the moment one person becomes infected until that person infects another person. The concept is similar to “generation gap” in demography, with new infections replacing births in a population. Originally applied to diseases such as measles where at least the first generations are clearly discernible, the concept has recently been extended to other diseases, such as influenza, where time order of infections is usually much less apparent.By formulating the relevant statistical questions within a simple yet basic mathematical model for infection spread, it is possible to derive theoretical properties of observations in various situations e.g. in “isolation”, in households, or during large outbreaks. In each case, it is shown that the sampling distribution of observations depends on a number of factors, usually not considered in the literature and that must be taken into account in order to achieve unbiased inference about the generation time distribution. Some implications of these findings for statistical inference methods in epidemic spread models are discussed.     

Paleoenvironmental conditions preceding the Messinian Salinity Crisis in the Central Mediterranean: Integrated data from the Upper Miocene Trave section (Italy)

Integrated data of calcareous plankton and benthic foraminifers from the pre-evaporitic interval of Trave section (Central Italy) allowed the reconstruction of surface and bottom-water conditions in the Central Mediterranean during the interval from 7.61 to 6.33 Ma, preceding the Messinian Salinity Crisis.Our data point out a three-step paleoenvironmental evolution. During the first stage (7.61-7.02 Ma) benthic foraminiferal assemblages depict stable, well-oxygenated and ventilated bottom-water conditions, while the surface water records variable temperature and high nutrient conditions, probably associated with strong seasonality. The second stage (7.02-6.70 Ma) points to unfavourable bottom-water condition, triggered by deep-sea stagnation. This is witnessed by a significant decrease in oxygen concentration and biotic diversity, and by the presence of stress-tolerant taxa. A general warming of the surface water and a strongly stratified water column, characterized by an expanded mixed layer, are also recorded.From 6.70 Ma onwards (third stage), a prominent change to more restricted, low-oxygenated, hypersaline conditions at the sea floor is testified by the total disappearance of deep-dwelling planktonic foraminifers and the increasing abundance of stress-tolerant species. Calcareous plankton reflects high instability of the surface water in terms of nutrients, temperature and salinity. During this stage the environmental deterioration reaches intermediate depths in the water column.The initial change toward a step-wise isolation of the Central Mediterranean bottom-waters is probably related to a general warming, responsible for a first slowing-down of the vertical circulation, favouring stratification of surface and intermediate waters and stagnation of bottom-waters. This warming is related to the restricted connection between the Mediterranean Sea and the Atlantic Ocean, which occurred since 7.146 Ma.In the Trave section, the isolation of bottom-waters most likely occurred at the same time as in other Mediterranean sections. However, due to the presence of a hiatus it cannot be excluded that it occurred with a delay of ~ 100 kyr, probably related to the shallower paleodepth of the basin.     

Comparison of micrometer‐ and scanning electron microscope‐based measurements of avian eggshell thickness

ABSTRACT The study of avian eggshell structure, including composition, pigmentation, thickness, and strength, has important ecological and economic implications. Previous investigators have used a variety of techniques to derive either direct measures or indirect estimates of eggshell thickness. Assessing the repeatability and method agreement of different techniques is necessary to permit comparison of eggshell thickness values from different studies on various genetic stocks, populations, and species. We recorded and analyzed measurements of eggshell thickness using two methods, micrometers and scanning electron microscopy (SEM), for several Palaeognathae and Neognathae taxa, including nonpasserines and passerines. Applying a tolerance‐interval approach, we found that repeatability of measurements for eggs with thinner shells (<300 μm, all Neognathae taxa) was worse than for eggs with thicker shells (Palaeognathae taxa), but was still statistically and biologically reasonable given that the relative magnitude of intramethod agreements was <11%. Our results support previous predictions that measurements made using a micrometer are comparable to those made using SEM. This finding is particularly important given the relative ease and cost efficiency of the micrometer method. Importantly, these new analyses can be used to validate the use of published data from previous studies of micrometer‐based eggshell thickness for both intra‐ and interspecific comparisons.