Fine-mapping of muscle weight QTL in LG/J and SM/J intercrosses

Genetic variation plays a substantial role in variation in strength, but the underlying mechanisms remain poorly understood. The objective of the present study was to examine the mechanisms underlying variation in muscle mass, a predictor of strength, between LG/J and SM/J strains, which are the inbred progeny of mice selected, respectively, for high and low body weight. We measured weight of five hindlimb muscles in LG/J and SM/J males and females, in F1 and F2 intercrosses, and in an advanced intercross (AI), F34, between the two. F2 mice were genotyped using 162 SNPs throughout the genome; F34 mice were genotyped at 3,015 SNPs. A twofold difference in muscle mass between the LG/J and SM/J mouse strains was observed. Integrated genome-wide association analysis in the combined population of F2 and AI identified 22 quantitative trait loci (QTL; genome-wide P < 0.05) affecting muscle weight on Chr 2 (2 QTL), 4, 5, 6 (7 QTL), 7 (4 QTL), 8 (4 QTL), and 11 (3 QTL). The LG/J allele conferred greater muscle weight in all cases. The 1.5-LOD QTL support intervals ranged between 0.3 and 13.4 Mb (median 3.7 Mb) restricting the list of candidates to between 5 and 97 genes. Selection for body weight segregated the alleles affecting skeletal muscle, the most abundant tissue in the body. Combination of analyses in an F2 and AI was an effective strategy to detect and refine the QTL in a genome-wide manner. The achieved resolution facilitates further elucidation of the underlying genetic mechanisms affecting muscle mass.

Download Full-text

Genomic prediction for growth using a low-density SNP panel in dromedary camels

Scientific Reports ◽

10.1038/s41598-021-87296-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Morteza Bitaraf Sani ◽

Javad Zare Harofte ◽

Mohammad Hossein Banabazi ◽

Saeid Esmaeilkhanian ◽

Ali Shafei Naderi ◽

...

Keyword(s):

Body Weight ◽

Birth Weight ◽

Sample Size ◽

Genetic Improvement ◽

Growth Traits ◽

P Value ◽

Dromedary Camels ◽

Genome Wide ◽

A Genome ◽

Daily Gain

AbstractFor thousands of years, camels have produced meat, milk, and fiber in harsh desert conditions. For a sustainable development to provide protein resources from desert areas, it is necessary to pay attention to genetic improvement in camel breeding. By using genotyping-by-sequencing (GBS) method we produced over 14,500 genome wide markers to conduct a genome- wide association study (GWAS) for investigating the birth weight, daily gain, and body weight of 96 dromedaries in the Iranian central desert. A total of 99 SNPs were associated with birth weight, daily gain, and body weight (p-value < 0.002). Genomic breeding values (GEBVs) were estimated with the BGLR package using (i) all 14,522 SNPs and (ii) the 99 SNPs by GWAS. Twenty-eight SNPs were associated with birth weight, daily gain, and body weight (p-value < 0.001). Annotation of the genomic region (s) within ± 100 kb of the associated SNPs facilitated prediction of 36 candidate genes. The accuracy of GEBVs was more than 0.65 based on all 14,522 SNPs, but the regression coefficients for birth weight, daily gain, and body weight were 0.39, 0.20, and 0.23, respectively. Because of low sample size, the GEBVs were predicted using the associated SNPs from GWAS. The accuracy of GEBVs based on the 99 associated SNPs was 0.62, 0.82, and 0.57 for birth weight, daily gain, and body weight. This report is the first GWAS using GBS on dromedary camels and identifies markers associated with growth traits that could help to plan breeding program to genetic improvement. Further researches using larger sample size and collaboration of the camel farmers and more profound understanding will permit verification of the associated SNPs identified in this project. The preliminary results of study show that genomic selection could be the appropriate way to genetic improvement of body weight in dromedary camels, which is challenging due to a long generation interval, seasonal reproduction, and lack of records and pedigrees.

Download Full-text

Discovery and refinement of muscle weight QTLs in B6 × D2 advanced intercross mice

Physiological Genomics ◽

10.1152/physiolgenomics.00055.2014 ◽

2014 ◽

Vol 46 (16) ◽

pp. 571-582 ◽

Cited By ~ 9

Author(s):

P. Carbonetto ◽

R. Cheng ◽

J. P. Gyekis ◽

C. C. Parker ◽

D. A. Blizard ◽

...

Keyword(s):

Inbred Strains ◽

Mouse Strains ◽

Missense Mutations ◽

Muscle Weight ◽

Hindlimb Muscles ◽

Hindlimb Muscle ◽

Causal Genes ◽

Snp Panel ◽

Genomic Regions ◽

Genetic Contributions

The genes underlying variation in skeletal muscle mass are poorly understood. Although many quantitative trait loci (QTLs) have been mapped in crosses of mouse strains, the limited resolution inherent in these conventional studies has made it difficult to reliably pinpoint the causal genetic variants. The accumulated recombination events in an advanced intercross line (AIL), in which mice from two inbred strains are mated at random for several generations, can improve mapping resolution. We demonstrate these advancements in mapping QTLs for hindlimb muscle weights in an AIL ( n = 832) of the C57BL/6J (B6) and DBA/2J (D2) strains, generations F8–F13. We mapped muscle weight QTLs using the high-density MegaMUGA SNP panel. The QTLs highlight the shared genetic architecture of four hindlimb muscles and suggest that the genetic contributions to muscle variation are substantially different in males and females, at least in the B6D2 lineage. Out of the 15 muscle weight QTLs identified in the AIL, nine overlapped the genomic regions discovered in an earlier B6D2 F2 intercross. Mapping resolution, however, was substantially improved in our study to a median QTL interval of 12.5 Mb. Subsequent sequence analysis of the QTL regions revealed 20 genes with nonsense or potentially damaging missense mutations. Further refinement of the muscle weight QTLs using additional functional information, such as gene expression differences between alleles, will be important for discerning the causal genes.

Download Full-text

Foot Length as a Predictor of Weight in Children up to Five Years

TAJ Journal of Teachers Association ◽

10.3329/taj.v31i2.41595 ◽

2019 ◽

Vol 31 (2) ◽

pp. 39-44

Author(s):

Md Shameem ◽

Nazneen Akhter Banu ◽

ANM Nurul Haque Bhuiyan ◽

Ariful Islam

Keyword(s):

Body Weight ◽

Linear Regression ◽

Regression Line ◽

The Body ◽

Critically Ill Children ◽

Linear Regression Line ◽

Foot Length ◽

Measured Weight ◽

Variable Weight

Weight measurement is essential for the management of pediatric patients to calculate the dose of the drugs. But it is not possible to move the child to a weighing scale for determination of body weight when the child is in a critical condition. The purpose of this study was to check if foot length correlates with child’s body weight in our situation and to devise a formula for prediction of weight based on foot– length observed. This Cross-sectional study was carried out in the Department of Pediatrics, Sir Salimullah Medical College, Mitford hospital, Dhaka over a period of 12 months between January 2008 and December 2008. A total of 300 children, between 0 day to five years, meeting the predefined eligibility criteria were included in the study. Using the available data, simple linear regression analysis was performed between the dependent variable weight and independent variable foot length. The estimated linear regression line was: Predicted weight (kg) = a+ [b× foot length]. Data were analyzed using correlation coefficient (r) between foot length and children’s weight. In this study correlation between foot length and weight (r) was 0.92(P<0.001) indicating a perfect linear relationship between them. In the present study determination of correlation (r2) was 0.85 meaning that 85% of the variability in weight might be explained by variation in foot length. The estimated linear regression line was: Predicted weight (kg) = - 4.64 + [1.12 X foot length], where- 4.64 was the intercept and 1.12 was the slope of the regression line. Comparison between measured weight and predicted weight revealed that94% of variation between measured weight and predicted weight was within ±2kg. More than half of the cases (58.3%) the above-mentioned variations were within ±1kg. This study concluded, there was a strong correlation between foot length and weight in children up to five years. The body weight in children from 0 days up to the age of 5 years can be predicted from foot length. Prediction of weight simply by foot-length measurement could be a great help to the health care provider including doctors and health workers for drug dose calculation in critically ill children. TAJ 2018; 31(2): 39-44

Download Full-text

Effects of altitude acclimatization on rat myoglobin. Changes in myoglobin content of skeletal and cardiac muscle

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1959.196.3.512 ◽

1959 ◽

Vol 196 (3) ◽

pp. 512-516 ◽

Cited By ~ 27

Author(s):

Adam Anthony ◽

Eugene Ackerman ◽

G. K. Strother

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Cardiac Muscle ◽

Water Content ◽

Skeletal Muscles ◽

The Body ◽

Continuous Exposure ◽

Weight Changes ◽

Body Weight Changes ◽

Muscle Weight

Analyses were made of myoglobin content of rat skeletal and cardiac muscle following continuous exposure to simulated altitudes of 18,000 feet for a 2–10-week period. About five dozen rats were used. Acclimatization was associated with an increase in the myoglobin concentration of thigh, diaphragm, gastrocnemius and heart muscles. Total myoglobin content, however, increased during acclimatization in cardiac muscle but not in the three skeletal muscles. This finding together with the body weight changes and muscle weight changes suggested that the increases in myoglobin concentration of skeletal muscle may be merely a reflection of a decreased water content of muscles.

Download Full-text

Contribution of Heritability and Epigenetic Factors to Skeletal Muscle Mass Variation in United Kingdom Twins

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-1219 ◽

2016 ◽

Vol 101 (6) ◽

pp. 2450-2459 ◽

Cited By ~ 25

Author(s):

Gregory Livshits ◽

Fei Gao ◽

Ida Malkin ◽

Maria Needhamsen ◽

Yudong Xia ◽

...

Keyword(s):

Skeletal Muscle ◽

Dna Methylation ◽

United Kingdom ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Decomposition Analysis ◽

Repeated Measurements ◽

Cross Sectional ◽

Genome Wide ◽

A Genome

Abstract Context: Skeletal muscle mass (SMM) is one of the major components of human body composition, with deviations from normal values often leading to sarcopenia. Objective: Our major aim was to conduct a genome-wide DNA methylation study in an attempt to identify potential genomic regions associated with SMM. Design: This was a mixed cross-sectional and longitudinal study. Setting: Community-based study. Participants: A total of 1550 middle-aged United Kingdom twins (monozygotic [MZ] and dizygotic [DZ]), 297 of which were repeatedly measured participated in the study. Main Outcome Measure: Appendicular lean mass assessed using dual-energy X-ray absorptiometry technology, and methylated DNA immunoprecipitation sequencing DNA methylation profiling genome-wide were obtained from each individual. Results: Heritability estimate of SMM, with simultaneous adjustment for covariates obtained using variance decomposition analysis, was h2 = 0.809 ± 0.050. After quality control and analysis of longitudinal stability, the DNA methylation data comprised of 723 029 genomic sites, with positive correlations between repeated measurements (Rrepeated = 0.114–0.905). Correlations between MZ and DZ twins were 0.51 and 0.38 at a genome-wide average, respectively, and clearly increased with Rrepeated. Testing for DNA methylation association with SMM in 50 discordant MZ twins revealed 36 081 nominally significant results, of which the top-ranked 134 signals (P < .01 and Rrepeated > 0.40) were subjected to replication in the sample of 1196 individuals. Seven SMM methylation association signals replicated at a false discovery rate less than 0.1, and these were located in or near genes DNAH12, CAND1, CYP4F29P, and ZFP64, which have previously been highlighted in muscle-related studies. Adjusting for age, smoking, and blood cell heterogeneity did not alter significance of these associations. Conclusion: This epigenome-wide study, testing longitudinally stable methylation sites, discovered and replicated a number of associations between DNA methylation at CpG loci and SMM. Four replicated signals were related to genes with potential muscle functions, suggesting that the methylome of whole blood may be informative of SMM variation.

Download Full-text

Osteodensitometric Characteristics of Bone Tissue in Women with Normal Body Weight

Journal of Anatomy and Histopathology ◽

10.18499/2225-7357-2021-10-3-108-111 ◽

2021 ◽

Vol 10 (3) ◽

pp. 108-111

Author(s):

I. G. Pashkova

Keyword(s):

Body Weight ◽

Bone Tissue ◽

Muscle Mass ◽

Bone Mineralization ◽

Lumbar Vertebrae ◽

The Body ◽

Mineral Density ◽

Normal Body ◽

Age Related ◽

Normal Body Weight

The aim of the study was to investigate age-related changes in bone mineralization indicators in the lumbar vertebrae in women with normal body weight living in the conditions of the Northern region.Material and methods. A complex somatometric examination and quantitative assessment of the bone tissue mineral density in the lumbar vertebrae were performed according to dual-energy X-ray absorptiometry of a group of Slavic women (n=127) with a normal body weight (BMI values from 18.5 to 24.9 kg/m2) aged 20 to 87 years, permanently residing in the Republic of Karelia. Statistical processing of the material was performed using the program "STATISTICA 6.0".Results. The BMI values in women increased significantly every decade of life. Direct correlations of mineral bone density (MBD) with the body length (r=0.46, p<0.001), with the body surface area (r=0.46, p<0.001), with absolute muscle mass (MM) (r=0.39, p<0.001), and with body mass (r=0.29, p<0.001) were revealed. No significant correlation with the adipose mass was found. The incidence of low MBD of the lumbar vertebrae was 48%: osteopenia was in 29%, osteoporosis was in 19% of women. The analysis of the component composition of the body in women with different levels of bone mass showed significant differences in the absolute content of muscle mass.Conclusion. In women with a normal BMI, body weight and muscle mass play an essential role in maintaining lumbar vertebrae bone mineral density.

Download Full-text

Genome-wide Association Analysis of Adaptation to Oxygen Stress in Nile Tilapia (Oreochromis Niloticus)

10.21203/rs.3.rs-62338/v1 ◽

2020 ◽

Author(s):

Xiaofei Yu ◽

Hendrik-Jan Megens ◽

Samuel B. Mengistu ◽

John W.M. Bastiaansen ◽

Han A. Mulder ◽

...

Keyword(s):

Body Weight ◽

Growth Stage ◽

Early Stage ◽

Nervous System Development ◽

Genome Wide Association ◽

Environment Interaction ◽

Genome Wide ◽

Hypoxic Environment ◽

A Genome ◽

Vegf Signalling

Abstract Background: Tilapia is one of the most abundant species in aquaculture. Hypoxia is known to depress growth rate, but the genetic mechanism by which this occurs is unknown. In this study, two groups consisting of 3140 fish that were raised in either aerated (normoxia) or non-aerated pond (nocturnal hypoxia). During grow out, fish were sampled five times to determine individual body weight (BW) gains. We applied a genome-wide association study to identify SNPs and genes associated with the hypoxic and normoxic environments in the 17th generation of a Genetically Improved Farmed tilapia population. Results: In the hypoxic environment, 36 SNPs associated with at least one of the five body weight measurements (BW1 till BW5), of which six, located between 19.48 Mb and 21.04 Mb on Linkage group (LG) 8, were significant for body weight in the early growth stage (BW1 to BW2). Further significant associations were found for BW in the later growth stage (BW3 to BW5), located on LG1 and LG8. Analysis of genes within the candidate genomic region suggested that MAPK and VEGF signalling were significantly involved in the later growth stage under the hypoxic environment. Well-known hypoxia-regulated genes such as igf1rb, rora, efna3 and aurk were also associated with growth in the later stage in the hypoxic environment. Conversely, 13 linkage groups containing 29 unique significant and suggestive SNPs were found across the whole growth period under the normoxic environment. A meta-analysis showed that 33 SNPs were significantly associated with BW across the two environments, indicating a shared effect independent of hypoxic or normoxic environment. Functional pathways involved in nervous system development and organ growth in the early stage, and oocyte maturation in the later stage.Conclusions: There are clear genotype-growth associations in both normoxic and hypoxic environments, although genome architecture involved changed over the growing period, indicating a transition in metabolism along the way. The involvement of pathways important in hypoxia especially at the later growth stage indicates a genotype-by-environment interaction, in which MAPK and VEGF signalling are important components.

Download Full-text

Review: Population Structure in Genetic Studies: Confounding Factors and Mixed Models

10.1101/092106 ◽

2016 ◽

Author(s):

Lana S. Martin ◽

Eleazar Eskin

Keyword(s):

Population Structure ◽

Mixed Models ◽

Genome Wide Association Study ◽

Association Studies ◽

Laboratory Mouse ◽

Mouse Strains ◽

Genetic Studies ◽

The Past ◽

Genome Wide ◽

A Genome

AbstractA genome-wide association study (GWAS) seeks to identify genetic variants that contribute to the development and progression of a specific disease. Over the past 10 years, new approaches using mixed models have emerged to mitigate the deleterious effects of population structure and relatedness in association studies. However, developing GWAS techniques to effectively test for association while correcting for population structure is a computational and statistical challenge. Using laboratory mouse strains as an example, our review characterizes the problem of population structure in association studies and describes how it can cause false positive associations. We then motivate mixed models in the context of unmodeled factors.

Download Full-text