Genome scan linkage analysis identifies quantitative trait loci affecting serum clinical–chemical traits in Korean native chicken

Alterations in robustness- and health-related traits lead to physiological changes, such as changes in the serum clinical chemical parameters in individuals. Therefore, clinical–chemical traits can be used as biomarkers to examine the health status of chickens. The aim of the present study was to detect the quantitative trait loci (QTLs) influencing eight clinical–chemical traits (glucose, total protein, creatinine, high-density lipoprotein cholesterol, total cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and α-amylase) in an F₁ nuclear families comprising 83 F₀ founders and 585 F₁ progeny of Korean native chickens. Genotypic data on 135 DNA markers representing 26 autosomes have been generated for this resource pedigree. The total length of the map was 2729.4 cM. We used a multipoint variance component linkage approach to identify QTLs for the traits. A significant QTL affecting serum α-amylase levels was identified on chicken chromosome (GGA) 7 [logarithm of odds (LOD) = 3.02, P value = 1.92 × 10^?4]. Additionally, we detected several suggestive linkage signals for the levels of total cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and creatinine on GGA 4, 12, 13, and 15. In this study, serum α-amylase levels related significant QTL was mapped on GGA7 and cholesterol, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and creatinine traits related suggestive QTLs were detected on GGA4, 12, 13 and 15, respectively. Further verification and fine mapping of these identified QTLs can provide valuable information for understanding the variations of clinical chemical trait in chickens.     

Results of a whole genome scan targeting QTL for growth and carcass traits in a Piétrain × Large White intercross

We herein report the results of a whole genome scan performed in a Piétrain × Large White intercross counting 525 offspring to map QTL influencing economically important growth and carcass traits. We report experiment-wide significant lod scores (> 4.6 for meatiness and fat deposition on chromosome SSC2, and for average daily gain and carcass length on chromosome SSC7. Additional suggestive lod scores (> 3.3) for fat deposition are reported on chromosomes SSC1, SSC7 and SSC13. A significant dominance deviation was found for the QTL on SSC1, while the hypothesis of an additive QTL could not be rejected for the QTL on SSC7 and SSC13. No evidence for imprinted QTL could be found for QTL other than the one previously reported on SSC2.     

A genome scan for loci affecting adipocyte size and number in abdominal fat in a White Duroc × Erhualian F2 resource population

Adipocyte size and number are correlated with fat deposition, which is of major concern to human health and pork producers. To identify quantitative trait loci (QTL) for adipocyte size and number in pigs, a total of 341 F2 animals at 240 days in a White Duroc × Erhualian cross were measured for the area, perimeters, volume and number of adipocyte in abdominal fat. A genome scan was performed on these animals and their parents and grandparents with 183 microsatellite markers spanning the pig genome. Five chromosomal regions showed effects on the traits measured, predominantly on adipocyte size, on pig chromosome (SSC) 1, 4, 7 and 9. Neither of these QTL has been reported before this study. The QTL for adipocyte size detected in this study perfectly correspond to the previously reported QTL for fatness traits on SSC1, 4 and 7. The most significant association was evidenced at 58 cM on SSC7. At the locus, the favorable allele decreasing adipocyte size was unusually originated from the obese Erhualian breed. Only a suggestive QTL was detected for adipocyte number on SSC9. The results shed new lights on the understanding of the genetic basis of fatness traits in pigs.     

A genome-wide scan for quantitative trait loci affecting serum glucose and lipids in a White Duroc × Erhualian intercross F2 population

Serum glucose and lipid levels are associated with diabetes mellitus and cardiovascular disease. The purpose of this study was to identify quantitative trait loci (QTL) for serum glucose and lipids in a White Duroc × Erhualian resource population. Serum glucose, glycosylated serum proteins (GSP), and serum lipid levels were measured in a total of 760 F₂ animals at 240 days. Strong positive correlations were observed between total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C)/high-density-lipoprotein cholesterol (HDL-C). A whole-genome scan was performed with 194 microsatellites covering the pig genome across the entire resource population, revealing 2 QTL for serum glucose and 15 QTL for serum lipids. Of them, three 1% genome-wide significant QTL were identified for LDL-C, TC, and triglycerides (TG) in an adjacent region (67–73 cM) on chromosome 2 (SSC2), and the QTL for LDL-C showed the largest effect with a 95% confidence interval of 5 cM. Another 1% genome-wide significant QTL was found for LDL-C at 87 cM on SSC8. Other QTL showed 5% genome-wide significant or suggestive effects on SSC4, 5, 7, 9, 11, 14, and 15. In total, five significant QTL for serum lipids and a suggestive QTL for GSP on SSC4 were identified for the first time in pigs. Most of the identified QTL are homologous to the previously reported QTL for serum lipids in humans and mice. As correlated traits, QTL for TC and LDL-C were always located in the same genomic regions. The results shed new light on studies of human atherosclerosis and cardiovascular-related diseases. R. Chen, J. Ren, and W. Li contributed equally to this work.     

The role of PET-CT scan with somatostatin analogue labelled with gallium-68 (⁶⁸Ga-DOTA-TATE PET-CT) in diagnosing patients with disseminated medullary thyroid carcinoma (MTC)

INTRODUCTION: Calcitonin is a very sensitive marker of medullary thyroid carcinoma (MTC). High concentrations of basal or pentagastrin stimulated calcitonin in patients with MTC is a signal of recurrence or metastatic disease. Detection of metastatic foci remains a diagnostic and therapeutic challenge. The aim of the study was to present examples of the use of ??Ga-DOTA-TATE PET-CT examinations in the diagnosis of patients with MTC and concomitant elevated serum calcitonin concentrations. Initially the study involved eight patients with MTC and elevated basal or stimulated calcitonin, in which earlier diagnostic imaging was negative for metastasis: neck ultrasound, chest and mediastinal CT scan, liver MRI, bone scintigraphy, and 1?F-FDG-PET. A total body scan was performed using ??Ga-DOTA-TATE PET-CT. Two patients with positive diagnostic imaging tests were referred for surgery including resection of cervical lymph nodes with histopathological examination for assessment of metastases. CONCLUSIONS: On the basis of the presented cases we conclude that PET-CT scan with somatostatin analogue labelled with gallium (??Ga-DOTA-TATE PET-CT) may be useful in the diagnostic imaging of patients with disseminated MTC.     

Fully-automated systematic toxicological analysis of drugs,poisons, and metabolites in whole blood,urine, and plasma by gas chromatography–full scan mass spectrometry

The availability of automated, rapid and reliable methods for the systematic toxicological analysis (STA) of drugs and poisons in biosamples is of great importance in clinical and forensic toxicology laboratories. Gas chromatography–continuous scan mass spectrometry (GC–MS) possesses a high potential in STA because of its selectivity and identification power. However, in order to develop a fully automated STA method based on GC–MS two main obstacles have to be overcome: (a) sample preparation is rather sophisticated owing to the need to isolate analytes from the aqueous matrix and to allow a correct GC repartition of polar analytes; (b) the large amount of information collected within a single analysis makes it difficult to isolate relevant analytical information (mass spectra of analytes) from the chemical noise. Using a bench-top GC–MS system equipped with a laboratory robot for sample preparation (the Hewlett-Packard 7686 PrepStation) and an original method for mass spectral purification, a fully automated STA procedure was developed involving isolation of drugs from the sample (whole blood with minimal pretreatment, plasma, urine) by means of solid-phase extraction, derivatization (trimethylsilylation) of the acidic–neutral and of the basic extracts, GC–MS analysis, processing of data, and reporting of results. Each step of the procedure, and the method for data analysis in particular, can be easily integrated with other existing STA methods based on GC–MS.     

A whole genome scan to detect quantitative trait loci for gestation length and sow maternal ability related traits in a White Duroc × Erhualian F2 resource population

Gestation length and maternal ability are important to improve the sow reproduction efficiency and their offspring survival. To map quantitative trait loci (QTL) for gestation length and maternal ability related traits including piglet survival rate and average body weight of piglets at weaning, more than 200 F2 sows from a White Duroc × Erhualian resource population were phenotyped. A genome-wide scan was performed with 194 microsatellite markers covering the whole pig genome. QTL analysis was carried out using a composite regression interval mapping method via QTL express. The results showed that total number of born piglets was significantly correlated with gestation length (r = -0.13, P < 0.05). Three QTL were detected on pig chromosome (SSC)2, 8 and 12 for gestation length. The QTL on SSC2 achieved the 5% genome-wide significant level and the QTL on SSC8 was consistent with previous reports. Four suggestive QTL were identified for maternal ability related traits including 1 QTL for survival rate of piglets at weaning on SSC8, 3 QTL for average body weight of piglet at weaning on SSC3, 11 and 13.     

The importance of context to the genetic architecture of diabetes-related traits is revealed in a genome-wide scan of a LG/J?��?SM/J murine model

Variations in diabetic phenotypes are caused by complex interactions of genetic effects, environmental factors, and the interplay between the two. We tease apart these complex interactions by examining genome-wide genetic and epigenetic effects on diabetes-related traits among different sex, diet, and sex-by-diet cohorts in a Mus musculus model. We conducted a genome-wide scan for quantitative trait loci that affect serum glucose and insulin levels and response to glucose stress in an F₁₆ Advanced Intercross Line of the LG/J and SM/J intercross (Wustl:LG,SM-G16). Half of each sibship was fed a high-fat diet and half was fed a relatively low-fat diet. Context-dependent genetic (additive and dominance) and epigenetic (parent-of-origin imprinting) effects were characterized by partitioning animals into sex, diet, and sex-by-diet cohorts. We found that different cohorts often have unique genetic effects at the same loci, and that genetic signals can be masked or erroneously assigned to specific cohorts if they are not considered individually. Our data demonstrate that the effects of genes on complex trait variation are highly context-dependent and that the same genomic sequence can affect traits differently depending on an individual??s sex and/or dietary environment. Our results have important implications for studies of complex traits in humans.     

A genome-wide scan for quantitative trait loci affecting limb bone lengths and areal bone mineral density of the distal femur in a White Duroc × Erhualian F<Subscript>2</Subscript> population

Background

Limb bone lengths and bone mineral density (BMD) have been used to assess the bone growth and the risk of bone fractures in pigs, respectively. It has been suggested that limb bone lengths and BMD are under genetic control. However, the knowledge about the genetic basis of the limb bone lengths and mineralisatinon is limited in pigs. The aim of this study was to identify quantitative trait loci (QTL) affecting limb bone lengths and BMD of the distal femur in a White Duroc × Erhualian resource population.

Results

Limb bone lengths and femoral bone mineral density (fBMD) were measured in a total of 1021 and 116 F₂ animals, respectively. There were strong positive correlations among the lengths of limb bones and medium positive correlations between the lengths of limb bones and fBMD. A whole-genome scan involving 183 microsatellite markers across the pig genome revealed 35 QTL for the limb bone lengths and 2 for femoral BMD. The most significant QTL for the lengths of five limb bones were mapped on two chromosomes affecting all 5 limb bones traits. One was detected around 57 cM on pig chromosome (SSC) 7 with the largest F-value of more than 26 and 95% confidence intervals of less than 5 cM, providing a crucial start point to identify the causal genes for these traits. The Erhualian alleles were associated with longer limb bones. The other was located on SSCX with a peak at 50–53 cM, whereas alleles from the White Duroc breed increased the bone length. Many QTL identified are homologous to the human genomic regions containing QTL for bone-related traits and a list of interesting candidate genes.

Conclusion

This study detected the QTL for the lengths of scapula, ulna, humerus and tibia and fBMD in the pig for the first time. Moreover, several new QTL for the pig femoral length were found. As correlated traits, QTL for the lengths of five limb bones were mainly located in the same genomic regions. The most promising QTL for the lengths of five limb bones on SSC7 merits further investigation.