Chicken Quantitative Trait lLoci for Growth and Body Composition Associated with the Very Low Density Apolipoprotein-II Gene

Very low density apolipoprotein-II (apoVLDL-II) is a major constituent of very low density lipoprotein and is involved in lipid transportation in chickens. The current study was designed to investigate the associations of an apoVLDL-II gene polymorphism on chicken growth and body composition traits. The Iowa Growth and Composition Resource Population was established by crossing broiler sires with dams from 2 unrelated highly inbred lines (Leghorn and Fayoumi). The F1 birds were intercrossed, within dam line, to produce 2 related F2 populations. Body weight and body composition traits were measured in the F2 population. Primers for the 5\u27-flanking region in apoVLDL-II were designed from database chicken genomic sequence. Single nucleotide polymorphisms (SNP) between parental lines were detected by DNA sequencing, and PCR-RFLP methods were then developed to genotype SNP in the F2 population. There was no polymorphism in the 492 bp sequenced between broiler and Leghorn. The apoVLDL-II polymorphism between broiler and Fayoumi was associated with multiple traits of growth and body composition in the 148 male F2 individuals, including BW, breast muscle weight, drumstick weight, and tibia length. This research suggests that apoVLDL-II or a tightly linked gene has broad effects on growth and development in the chicken

Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations in the survival motor neuron 1 (SMN1) gene. Recent breakthroughs in preclinical research have highlighted several potential novel therapies for SMA, increasing the need for robust and sensitive clinical trial platforms for evaluating their effectiveness in human patient cohorts. Given that most clinical trials for SMA are likely to involve young children, there is a need for validated molecular biomarkers to assist with monitoring disease progression and establishing the effectiveness of therapies being tested. Proteomics technologies have recently been highlighted as a potentially powerful tool for such biomarker discovery. METHODS: We utilized label-free proteomics to identify individual proteins in pathologically-affected skeletal muscle from SMA mice that report directly on disease status. Quantitative fluorescent western blotting was then used to assess whether protein biomarkers were robustly changed in muscle, skin and blood from another mouse model of SMA, as well as in a small cohort of human SMA patient muscle biopsies. RESULTS: By comparing the protein composition of skeletal muscle in SMA mice at a pre-symptomatic time-point with the muscle proteome at a late-symptomatic time-point we identified increased expression of both Calreticulin and GRP75/Mortalin as robust indicators of disease progression in SMA mice. We report that these protein biomarkers were consistently modified in different mouse models of SMA, as well as across multiple skeletal muscles, and were also measurable in skin biopsies. Furthermore, Calreticulin and GRP75/Mortalin were measurable in muscle biopsy samples from human SMA patients. CONCLUSIONS: We conclude that label-free proteomics technology provides a powerful platform for biomarker identification in SMA, revealing Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers capable of reporting on disease progression in samples of muscle and skin

Genome-Wide Linkage Analysis to Identify Chromosomal Regions Affecting Phenotypic Traits in the Chicken. I. Growth and Average Daily Gain

Two informative chicken F2 populations based on crosses between a broiler breeder male line and dams from genetically distinct, highly inbred (\u3e99%) chicken lines, the Leghorn G-B2 and Fayoumi M15.2, have been used for genome-wide linkage and QTL analysis. Phenotypic data on 12 body composition traits (breast muscle weight, breast muscle weight percentage, abdominal fat weight, abdominal fat weight percentage, heart weight, heart weight percentage, liver weight, liver weight percentage, spleen weight, spleen weight percentage, and drumstick weight, and drumstick weight percentage) were collected. Birds were genotyped for 269 microsatellite markers across the genome. The QTL Express program was used to detect QTL for body composition traits. Significant levels were obtained using the permutation test. For the twelve traits, a total of 61 (Gga 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 18, 24, and Z) and 45 (Gga 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 15, 17, and E46) significant QTL were detected at the 5% chromosome-wise significance level, of which 19 and 11 were significant at the 5% genome-wise level for the broiler-Leghorn cross and broiler-Fayoumi cross, respectively. Phenotypic variation for each trait explained by all QTL across the genome ranged from 3.22 to 33.31% in the broiler-Leghorn cross and 4.83 to 47.12% in broiler-Fayoumi cross. Distinct QTL profiles between the 2 crosses were observed for most traits. Cryptic alleles were detected for each trait. Potential candidate genes within the QTL region for body composition traits at the 1% chromosome-wise significance level were identified from databases for future association study. The results of the current study will increase the knowledge of genetic markers associated with body composition traits and aid the process of identifying causative genes. Knowledge of beneficial genetic variation can be incorporated in breeding programs to enhance genetic improvement through marker-assisted selection in chickens

Chicken Quantitative Trait Loci for Growth and Body Composition Associated with Transforming Growth Factor-β Genes1

Transforming growth factor-β (TGF-β) belongs to a large family of multifunctional growth factors that regulate a broad spectrum of biological activities involved in morphogenesis, development, and differentiation. The current study was designed to investigate the effects of TGF-β genes on chicken growth and body composition traits. The Iowa Growth and Composition Resource Population was established by crossing broiler sires with dams from two unrelated highly inbred lines (Leghorn and Fayoumi). The F1 birds were intercrossed, within dam line, to produce two related F2 populations. Body weight and body composition traits were measured in the F 2 population. Primers for TGF-β2, TGF-β3, and TGF-β4 were designed from database chicken sequence. Polymorphisms between parental lines were detected by DNA sequencing, and PCR-RFLP methods were then developed to screen the F2 population. The TGF-β2 polymorphisms between broiler and Leghorn and the TGF-β4 polymorphism between broiler and Fayoumi were associated with traits of skeletal integrity, such as tibia length, bone mineral content, bone mineral density, and the percentage of each measure to BW. The TGF-β3 polymorphism between broilers and Leghorns was associated with traits of growth and body composition, such as BW, average daily gain, weight of breast muscle, abdominal fat pad and spleen, as well as the percentage of these organ weights to BW, and the percentage of shank weight and length to BW. The current research supports the broad effects of TGF-β genes on growth and development of chickens

Genome-Wide Linkage Analysis to Identify Chromosomal Regions Affecting Phenotypic Traits in the Chicken. II. Body Composition

The current study is a comprehensive genome analysis to detect QTL affecting metabolic traits in chickens. Two unique F2 crosses generated from a commercial broiler male line and 2 genetically distinct inbred lines (Leghorn and Fayoumi) were used in the present study. The plasma glucagon, insulin, lactate, glucose, tri-iodothyronine, thyroxine, insulin-like growth factor I, and insulin-like growth factor II concentrations at 8 wk were measured in the 2 F2 crosses. Birds were genotyped for 269 microsatellite markers across the entire genome. The program QTL Express was used for QTL detection. Significance levels were obtained using the permutation test. For the 10 traits, a total of 6 and 9 significant QTL were detected at a 1% chromosome-wise significance level, of which 1 and 6 were significant at the 5% genome-wise level for the broiler-Leghorn cross and broiler-Fayoumi cross, respectively. Most QTL for metabolic traits in the present study were detected in Gga 2, 6, 8, 9, 13, and Z for the broiler-Leghorn cross and Gga 1, 2, 4, 7, 8, 13, 17, and E47 for the broiler-Fayoumi cross. Phenotypic variation for each trait explained by all QTL across genome ranged from 2.73 to 14.08% in the broiler-Leghorn cross and from 6.93 to 21.15% in the broiler-Fayoumi cross. Several positional candidate genes within the QTL region for metabolic traits at the 1% chromosome-wise significance level are biologically associated with the regulation of metabolic pathways of insulin, triiodothyronine, and thyroxine

Insulin-Like Growth Factor-I Gene Polymorphism Associations with Growth, Body Composition, Skeleton Integrity, and Metabolic Traits

Molecular genetic selection on individual genes is a promising method to genetically improve economically important traits in chickens. A resource population was developed to study the genetics of growth, body composition, skeletal integrity, and metabolism traits. Broiler sires were crossed to dams of 2 diverse, highly inbred lines (Leghorn and Fayoumi), and the F1 birds were intermated by dam line to produce broiler-Leghorn and broiler-Fayoumi F2 offspring. Growth, body composition, skeletal integrity, and hormonal and metabolic factors were measured in 713 F2 individuals. Insulin-like growth factor-I (IGF1) was selected for study as a biological and positional candidate gene. A single nucleotide polymorphism (SNP) was identified between the founder lines in the IGF1 promoter region, and a PCR-RFLP assay was developed. A mixed model was used to statistically analyze associations of IGF1-SNP1 with phenotypic traits. The IGF1-SNP1 had significant associations with most recorded traits, except metabolic traits. Strong interactions between the IGF1 gene and genetic background on growth traits in the 2 F2 populations suggest that genetic interaction is an important aspect for consideration before using the IGF1-SNP1 in marker-assisted selection programs. Several beneficial effects (improved growth, increased breast muscle weight, decreased abdominal fat, and enhanced skeletal integrity) associated with 1 allele indicate the presence of 1 or more loci near IGF1-SNP1 controlling biologically diverse and economically important traits in chickens

Genome-Wide Linkage Analysis to Identify Chromosomal Regions Affecting Phenotypic Traits in the Chicken. III. Skeletal Integrity

Two unique chicken F2 populations generated from a broiler breeder male line and 2 genetically distinct inbred (\u3e99%) chicken lines (Leghorn and Fayoumi) were used for whole genome QTL analysis. Twelve phenotypic skeletal integrity traits (6 absolute and 6 relative traits) were measured or calculated, including bone mineral content, bone mineral density, tibia length, shank length, shank weight, and shank length:shank weight. All traits were also expressed as a percentage of BW at 8 wk of age. Birds were genotyped for 269 microsatellite markers across the entire genome. The QTL affecting bone traits in chickens were detected by the QTL express program. Significance levels were obtained using the permutation test. For the 12 traits, a total of 56 significant QTL were detected at the 5% chromosome-wise significance level, of which 14 and 10 were significant at the 5% genome-wise level for the broiler-Leghorn cross and broiler-Fayoumi cross, respectively. Phenotypic variation for each trait explained by all detected QTL across the genome ranged from 12.0 to 35.6% in the broiler-Leghorn cross and 2.9 to 31.3% in the broiler-Fayoumi cross. Different QTL profiles identified between the 2 related F2 crosses for most traits suggested that genetic background is an important factor for QTL analysis. Study of associations of biological candidate genes with skeletal integrity traits in chickens will reveal new knowledge of understanding biological process of skeletal homeostasis. The results of the current study have identified markers for bone strength traits, which may be used to genetically improve skeletal integrity in chickens by MAS, and to identify the causal genes for these traits

Nuclear structure functions at a future electron-ion collider

The quantitative knowledge of heavy nuclei's partonic structure is currently limited to rather large values of momentum fraction x-robust experimental constraints below x similar to 10(-2) at low resolution scale Q(2) are particularly scarce. This is in sharp contrast to the free proton's structure which has been probed in Deep Inelastic Scattering (DIS) measurements down to x similar to 10(-5) at perturbative resolution scales. The construction of an electron-ion collider (EIC) with a possibility to operate with a wide variety of nuclei, will allow one to explore the low-x region in much greater detail. In the present paper we simulate the extraction of the nuclear structure functions from measurements of inclusive and charm reduced cross sections at an EIC. The potential constraints are studied by analyzing simulated data directly in a next-toleading order global fit of nuclear Parton Distribution Functions based on the recent EPPS16 analysis. A special emphasis is placed on studying the impact an EIC would have on extracting the nuclear gluon parton distribution function, the partonic component most prone to nonlinear effects at low Q(2). In comparison to the current knowledge, we find that the gluon parton distribution function can be measured at an EIC with significantly reduced uncertainties.Peer reviewe