Quantifying genomic imprinting in the presence of linkage

Genomic imprinting decreases the power of classical linkage analysis, in which paternal and maternal transmissions of marker alleles are equally weighted. Several methods have been proposed for taking genomic imprinting into account in the model-free linkage analysis of binary traits. However, none of these methods are suitable for the formal identification and quantification of genomic imprinting in the presence of linkage. In addition, the available methods are designed for use with pure sib-pairs, requiring artificial decomposition in cases of larger sibships, leading to a loss of power. We propose here the maximum likelihood binomial method adaptive for imprinting (MLB-I), which is a unified analytic framework giving rise to specific tests in sibships of any size for (i) linkage adaptive to imprinting, (ii) genomic imprinting in the presence of linkage, and (iii) partial versus complete genomic imprinting. In addition, we propose an original measure for quantifying genomic imprinting. We have derived and validated the distribution of the three tests under their respective null hypotheses for various genetic models, and have assessed the power of these tests in simulations. This method can readily be applied to genome-wide scanning, as illustrated here for leprosy sibships. Our approach provides a novel tool for dissecting genomic imprinting in model-free linkage analysis, and will be of considerable value for identifying and evaluating the contribution of imprinted genes to complex diseases.     

Brief communication: Body mass index,body adiposity index,and percent body fat in asians

Human obesity is a growing epidemic throughout the world. Body mass index (BMI) is commonly used as a good indicator of obesity. Body adiposity index (BAI = hip circumference (cm)/stature (m)^1.5 ? 18), as a new surrogate measure, has been proposed recently as an alternative to BMI. This study, for the first time, compares BMI and BAI for predicting percent body fat (PBF; estimated from skinfolds) in a sample of 302 Buryat adults (148 men and 154 women) living in China. The BMI and BAI were strongly correlated with PBF in both men and women. The correlation coefficient between BMI and PBF was higher than that between BAI and PBF for both sexes. For the linear regression analysis, BMI better predicted PBF in both men and women; the variation around the regression lines for each sex was greater for BAI comparisons. For the receiver operating characteristic (ROC) analysis, the area under the ROC curve for BMI was higher than that for BAI for each sex, which suggests that the discriminatory capacity of the BMI is higher than the one of BAI. Taken together, we conclude that BMI is a more reliable indicator of PBF derived from skinfold thickness in adult Buryats. Am J Phys Anthropol 152:294–299, 2013. © 2013 Wiley Periodicals, Inc.     

Analysis of Peg1/Mest imprinting in the mouse

 In the mouse, Peg1/Mest is widely expressed in mesoderm-derived tissues. In separate studies, it has been shown to be maternally imprinted, that is, only the paternally inherited allele is active in mice and in humans. Here, we provide evidence that Peg1/Mest is expressed at very low levels in all tissues of adult mice as assessed by RT-PCR. Moreover, by using species-specific polymorphisms in the Peg1/Mest sequence we can demonstrate that in adult mice the gene remains imprinted in all of these tissues. Received: 24 November 1997 / Accepted: 11 February 1998     

Genetics of adult body mass and maintenance of adult body mass in captive baboons (Papio hamadryas subspecies)

Adult body mass and changes in mass during an individual's life are important indicators of general health and reproductive fitness. Therefore, characterization of the factors that influence normal variation in body mass has important implications for colony management and husbandry. The main objective of this study was to quantify the genetic contribution to adult body mass and its maintenance in baboons. Intra-individual mean and variance in body mass were calculated from multiple weight measures available for each of 1,614 animals at least 10 years of age. Heritabilities were estimated using maximum likelihood methods. Mean adult body mass had a significant heritability (50%) as did variance in adult body mass (12%). The sexes differed in several respects: on average females were smaller than males and had greater variability in adult body mass; mean and variance in body mass increased with age in females only; and number of offspring showed a significant positive relationship with body mass in females only. There were significant differences between subspecies in body mass as well as ability to maintain body mass. These results indicate that there is a significant genetic influence on body mass and its maintenance, and suggest that different factors influence changes in body mass with age as well as body mass maintenance in male and female baboons. Am. J. Primatol. 42:281–288, 1997. © 1997 Wiley-Liss, Inc.     

On the association of common and rare genetic variation influencing body mass index: a combined SNP and CNV analysis

Background

As the architecture of complex traits incorporates a widening spectrum of genetic variation, analyses integrating common and rare variation are needed. Body mass index (BMI) represents a model trait, since common variation shows robust association but accounts for a fraction of the heritability. A combined analysis of single nucleotide polymorphisms (SNP) and copy number variation (CNV) was performed using 1850 European and 498 African-Americans from the Study of Addiction: Genetics and Environment. Genetic risk sum scores (GRSS) were constructed using 32 BMI-validated SNPs and aggregate-risk methods were compared: count versus weighted and proxy versus imputation.

Results

The weighted SNP-GRSS constructed from imputed probabilities of risk alleles performed best and was highly associated with BMI (p = 4.3×10⁻¹⁶) accounting for 3% of the phenotypic variance. In addition to BMI-validated SNPs, common and rare BMI/obesity-associated CNVs were identified from the literature. Of the 84 CNVs previously reported, only 21-kilobase deletions on 16p12.3 showed evidence for association with BMI (p = 0.003, frequency = 16.9%), with two CNVs nominally associated with class II obesity, 1p36.1 duplications (OR = 3.1, p = 0.009, frequency 1.2%) and 5q13.2 deletions (OR = 1.5, p = 0.048, frequency 7.7%). All other CNVs, individually and in aggregate, were not associated with BMI or obesity. The combined model, including covariates, SNP-GRSS, and 16p12.3 deletion accounted for 11.5% of phenotypic variance in BMI (3.2% from genetic effects). Models significantly predicted obesity classification with maximum discriminative ability for morbid-obesity (p = 3.15×10⁻¹⁸).

Conclusion

Results show that incorporating validated effect sizes and allelic probabilities improve prediction algorithms. Although rare-CNVs did not account for significant phenotypic variation, results provide a framework for integrated analyses.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-368) contains supplementary material, which is available to authorized users.     

Resistin levels are related to fat mass,but not to body mass index in children

The relationship of resistin levels with obesity remains unclear. The aim of this study was to determine resistin levels in prepubertal children and adolescents and evaluate their association with anthropometric parameters and body composition. The study population included 420 randomly selected 6–8-year-old children and 712 children aged 12–16 years. Anthropometric data were measured and body mass index (BMI) and waist-to-hip and waist-to-height ratios were calculated. Body composition was assessed using an impedance body composition analyzer. Serum resistin levels were determined using a multiplexed bead immunoassay. Resistin levels were not significantly different between sexes. No significant differences in serum resistin concentrations were found between obese, overweight, and normal weight children at any age, and no significant correlations were observed between resistin concentrations and weight or BMI. However, resistin levels showed a significant positive correlation with fat mass in 12–16-year-old children, particularly in girls. In addition to describing serum resistin levels in prepubertal children and adolescents, our study suggests that resistin is related to body fat rather than to BMI in adolescents.     

Weight-height relationships and body mass index: some observations from the Diverse Populations Collaboration

Body mass index (BMI, weight (kg)/height (m)(2)) is the most widely used weight-height index worldwide. This universal use of BMI assumes that the rationale for its use is universally applicable. We examine two possible rationales for using BMI as a universal measure. The first rationale is that BMI is strongly correlated with weight, but is independent of height. The second rationale is that BMI correctly captures the relationship between weight and height, which implies that the slope of log weight regressed on log height is 2. We examined the weight-height relationship in 25 diverse population samples of men and women from the US, Europe, and Asia. The analysis included 72 subgroups with a total of 385,232 adults aged 25 years and older. Although BMI was highly correlated with weight in all studies, a significant, negative correlation between BMI and height was found in 31 out of 40 subgroups of men (r=-0.004 to -0.133) and 32 of 32 groups of women (r=-0.016 to -0.205). When log weight was regressed on log height, the 95% confidence intervals (CI) of the slopes did not include 2 in 25 out of 40 male subgroups. The summary estimate of the slopes across studies of men was 1.92 (95% CI, 1.87-1.97). For women, slopes were lower than 2 in 28 of 32 subgroups with a summary estimate of 1.45 (95% CI, 1.39-1.51). In most of the populations, BMI is not independent of height; weight does not universally vary with the square of height; and the relationship between weight and height differs significantly between males and females. The use of a single BMI standard for both men and women cannot be justified on the basis of weight-height relationships.     

Maternal uniparental disomy 14 dissection of the phenotype with respect to rare autosomal recessively inherited traits, trisomy mosaicism, and genomic imprinting

The phenotype of maternal uniparental disomy of chromosome 14 (upd(14)mat) is characterized by pre and postnatal growth retardation, early onset of puberty, joint laxity, motor delay, and minor dysmorphic features of the face, hands, and feet. Based on a clinical analysis of 24 cases extracted from the literature the phenotype of upd(14)mat was dissected with respect to each symptom's most likely primary causative: trisomy mosaicism, rare autosomal recessively inherited traits, and the impact of known imprinted genes located on chromosome 14q32. As a result, primary factors are confined placental mosaicism for prenatal growth retardation and one or more imprinted genes, which contribute to the reduced final height by accelerated skeletal maturation. As a secondary effect the latter might also cause early onset of puberty. Other secondary effects might be postnatal adaptation problems associated with neurological deficits such as muscular hypotonia due to premature delivery and reduced birthweight and most dysmorphic features as a consequence of subtle skeletal abnormalities and muscular hypotonia. Considering the rarity of traits such as cleft palate, trisomy mosaicism in the fetus is more likely causative than homozygosity of autosomal recessively inherited mutations. Totally, the variable phenotype of upd(14)mat is mainly the consequence of trisomy mosaicism and genomic imprinting. Rare traits might be due to homozygosity of autosomal recessively inherited mutations.     

Genome-wide analysis of genomic imprinting in the endosperm and allelic variation in flax

Genomic imprinting is an epigenetic phenomenon that causes biased expression of maternally and paternally inherited alleles. In flowering plants, genomic imprinting predominantly occurs in the triploid endosperm and plays a vital role in seed development. In this study, we identified 248 candidate imprinted genes including 114 maternally expressed imprinted genes (MEGs) and 134 paternally expressed imprinted genes (PEGs) in flax (Linum usitatissimum L.) endosperm using deep RNA sequencing. These imprinted genes were neither clustered in specific chromosomal regions nor well conserved among flax and other plant species. MEGs tended to be expressed specifically in the endosperm, whereas the expression of PEGs was not tissue-specific. Imprinted single nucleotide polymorphisms differentiated 200 flax cultivars into the oil flax, oil-fiber dual purpose flax and fiber flax subgroups, suggesting that genomic imprinting contributed to intraspecific variation in flax. The nucleotide diversity of imprinted genes in the oil flax subgroup was significantly higher than that in the fiber flax subgroup, indicating that some imprinted genes underwent positive selection during flax domestication from oil flax to fiber flax. Moreover, imprinted genes that underwent positive selection were related to flax functions. Thirteen imprinted genes related to flax seed size and weight were identified using a candidate gene-based association study. Therefore, our study provides information for further exploration of the function and genomic variation of imprinted genes in the flax population.     

The use of chimeric mice in studying the effects of genomic imprinting

This is a review of the data of clonal analysis of developing tissues in parthenogenetic and androgenetic chimeric mice. The time and causes of death of the parthenogenetic and androgenetic cell clones in chimeras are considered. The data obtained suggest that the development of cell clones, derivatives of the mesoderm and endoderm, is determined by the expression of alleles of the imprinted loci of paternal chromosomes, while the formation of cell clones, derivatives of the ectoderm, depends on the expression of other imprinted loci of maternal chromosomes. The death of androgenetic and parthenogenetic (gynogenetic) mammalian embryos is due to the lack of the expression of certain imprinted loci of the maternal and paternal genome, respectively.     

Evaluation of body mass index as a prognostic indicator from two rough‐toothed dolphin (Steno bredanensis) mass strandings in Florida

Rough‐toothed dolphins (Steno bredanensis) are a common mass stranding species in Florida. These large stranding events typically include a small number of sick or injured individuals and a much larger number of healthy individuals, making rapid triage essential. Little data exist on rehabilitation outcomes, and historically, successful outcomes are limited. Furthermore, very little data exist on the feeding habits and dietary needs of this species. This study compared morphology and body mass index (BMI) in two rough‐toothed dolphin mass stranding events in Florida: August 2004 (n = 36) and March 2005 (n = 32). The two groups were significantly different in morphologic measurements, with age and gender‐adjusted intake BMI significantly (p < .01) different (2004 = 0.34 ± 0.02; 2005 = 0.41 ± 0.02) between groups. Ten animals from 2005 had weights tracked throughout the rehabilitation process and demonstrated an initial drop in BMI followed by an increase and a plateau prior to release. When comparing initial BMI by stranding outcome, individuals that were rehabilitated and released had a significantly (p = .03) higher BMI than individuals who were euthanized. However, there was no difference between dolphins that died of natural causes (p = .56) and animals successfully rehabilitated. Analysis of BMI can be a useful marker in triage during a stranding, when resources are limited to identify individuals most likely to survive, as well as in determining the appropriate body condition for release. The data reported here can provide guidance on evaluating the nutritive status on this uncommon species that would otherwise be difficult to obtain among wild populations.     

不同身体质量指数人群肠道菌群结构及共存网络解析

[背景] 人体能量稳态失衡表现为体重过轻、超重和肥胖,肠道菌群与人体能量稳态的维持有关,但不同身体质量指数（Body Mass Index,BMI）人群的肠道菌群特征仍需进一步探究。[目的] 基于美国肠道计划公开数据库,解析4类BMI人群肠道菌群的特征,并探究4类BMI人群肠道菌群共存网络特征及差异,为基于肠道菌群来干预肥胖及体重过轻等不健康状态提供新的理论依据。[方法] 从美国肠道计划数据集中筛选具有BMI信息的肠道菌群样本,并根据世界卫生组织规定的BMI划分标准将筛选后的样本分为4类：体重过轻（BMI<18.5 kg/m²）,正常体重（18.5 kg/m²2）,超重（25 kg/m²2）,肥胖（BMI>30 kg/m²）;通过计算和比较肠道菌群的α多样性和β多样性探究4类BMI人群肠道菌群的整体结构特征及差异;通过多元线性回归模型对不同BMI分类与肠道菌群进行相关性分析,并且将地域、年龄、性别因素作为混杂因素加入到模型中进行校正;采用SparCC分别计算4类BMI人群肠道菌群中菌属相关性,并分别构建肠道菌群共存网络。[结果] 经过Wilcoxon秩和检验,发现体重过轻、超重、肥胖人群的肠道菌群α多样性都显著低于正常体重人群;β多样性分析结果表明4类BMI人群肠道菌群的整体结构存在显著差异;4类BMI人群肠道中厚壁菌门（Firmicutes）和拟杆菌门（Bacteroidetes）的相对含量无显著差异;通过MaAsLin分析,并且将地域、年龄、性别因素作为混杂因素加入到模型中进行校正,共得到49个与BMI类型显著相关的物种;4类BMI人群肠道菌群共存网络的拓扑结构具有一定差异,体重过轻和正常体重人群肠道菌群共存网络的复杂度较高,超重和肥胖人群肠道菌群共存网络的复杂度较低。[结论] 4类BMI人群肠道菌群的多样性、整体结构和共存网络间均存在差异。     

Mexican body mass index values in the late-19th-century American West

No research has been done on the body mass index values of the 19th-century Mexican population. This paper introduces a new data source of 19th-century Mexican male inmates in American prisons and finds that the majority of Mexican body mass was in the normal range (18.5-24.9). Few Mexicans were underweight or obese by modern standards. Body mass varied little (0-0.9 units) by occupations possibly because criminals probably came from the lower end of the socioeconomic distribution; however, it did vary with crimes for which inmates were incarcerated.     

Age variations in the relation of body mass indices to estimates of body fat and muscle mass

In some chronic disease studies, distinctions have been made regarding the importance of body mass index (BMI) as a risk factor in younger versus older men and women. In order to determine the significance of these differences in BMI-disease associations, we determined the extent of age-dependent variations in the relation of BMIs to body composition in large probability samples of U.S. men and women from the First and Second U.S. National Health and Nutrition Examination Surveys (NHANES I and II). BMIs are more highly correlated with estimates of body fat in younger than in older men and women, and with muscle mass in older than in younger adults. Caution should be exercised in interpreting the significance of BMI as a risk factor for chronic disease, particularly in comparison of age groups.     

Variation in body mass index among Polish adults: effects of sex, age, birth cohort, and social class

Remains of 15 hominids were recovered within a Mousterian archaeological context in the cave of Qafzeh, Israel. Dated to ca. 95 kyr BP, this skeletal material has been crucial for understanding biological, chronological, and cultural aspects of anatomically modern ancient Homo sapiens. The high proportion of children (N = 8) in Qafzeh Cave is unique among Middle Palaeolithic sites and encourages the search for skeletal evidence of disease and trauma. We report on the case of one child, Qafzeh 12, ca. 3 years old (according to modern human reference standards), who manifests some outstanding skeletal abnormalities that indicate hydrocephalus.     

Identification and reciprocal introgression of a QTL affecting body mass in mice

The aim of this study was to examine the effects of a QTL in different genetic backgrounds. A QTL affecting body mass on chromosome 6 was identified in an F₂ cross between two lines of mice that have been divergently selected for this trait. The effect of the QTL on mass increased between 6 and 10 weeks of age and was not sex-specific. Body composition analysis showed effects on fat-free dry body mass and fat mass. To examine the effect of this QTL in different genetic backgrounds, the high body mass sixth chromosome was introgressed into the low body mass genetic background and vice versa by repeated marker-assisted backcrossing. After three generations of backcrossing, new F₂ populations were established within each of the introgression lines by crossing individuals that were heterozygous across the sixth chromosome. The estimated additive effect of the QTL on 10-week body mass was similar in both genetic backgrounds and in the original F₂ population (i.e., ~0.4 phenotypic standard deviations); no evidence of epistatic interaction with the genetic background was found. The 95% confidence interval for the location of the QTL was refined to a region of approximately 7 cM between D6Mit268 and D6Mit123.     

Scaling of the limb long bones to body mass in terrestrial mammals

Long‐bone scaling has been analyzed in a large number of terrestrial mammals for which body masses were known. Earlier proposals that geometric or elastic similarity are suitable as explanations for long‐bone scaling across a large size range are not supported. Differential scaling is present, and large mammals on average scale with lower regression slopes than small mammals. Large mammals tend to reduce bending stress during locomotion by having shorter limb bones than predicted rather than by having very thick diaphyses, as is usually assumed. The choice of regression model used to describe data samples in analyses of scaling becomes increasingly important as correlation coefficients decrease, and theoretical models supported by one analysis may not be supported when applying another statistical model to the same data. Differences in limb posture and locomotor performance have profound influence on the amount of stress set up in the appendicular bones during rigorous physical activity and make it unlikely that scaling of long bones across a large size range of terrestrial mammals can be satisfactorily explained by any one power function. J. Morphol. 239:167–190, 1999. © 1999 Wiley‐Liss, Inc.     

Genetic Variability of Adult Body Mass Index: A Longitudinal Assessment in Framingham Families

Objective: To explore the contribution of genetics to the mean, SD, maximum value, maximum less the mean, and change over time in body mass index (BMI) and the residual of body weight after adjustment for height. BMI is frequently used as a general indicator of obesity because of its ease and reliability in ascertainment. Cross‐sectional twin and family studies have shown a moderate‐to‐substantial genetic component for BMI. However, the contribution of genetics to the long‐term average, variability, or change over time in BMI is less clear. Research Methods and Procedures: Longitudinal data from the Framingham heart study were used to create pedigrees of age‐matched individuals. Heritability estimates were derived using variance‐decomposition methods on a total of 1051 individuals from 380 extended pedigrees followed for a period of 20 years. All subjects were followed from approximately age 35 to 55 years. Results: Moderate heritability estimates were found for the mean BMI (h² = 0.37), maximum BMI (h² = 0.40), and the mean residual of body weight (h² = 0.36). Low heritability estimates (h² ? 0.20) were found for the maximum less the mean in BMI and the SDs of BMI and residual of body weight. No additive genetic contribution was found for the average change over time in BMI or the residual of body weight. Discussion: These findings suggest that there is a significant genetic component for the magnitude of BMI throughout an individual's middle‐adult years; however, little evidence was found for a genetic contribution to the variability or rate of change in an individual's BMI.     

Correlation between glucocorticoid receptor binding parameters, blood pressure, and body mass index in a healthy human population

Correlation between the glucocorticoid receptor (GR) number and affinity for the ligand, as well as the relationship between these equilibrium binding parameters and body mass index, blood pressure, and age were examined in peripheral blood mononuclear cells (PBMC) of healthy human subjects. It was found that the only statistically significant correlation was that between the GR number per cell and equilibrium dissociation constant, K(d) (r = 0.84, p < 0.0001). This observation implies the existence of a compensatory mechanism providing for lower GR affinity in individuals that have more receptor sites in circulating mononuclear cells and vice versa. This compensatory phenomenon together with considerable interindividual variation (GR number per cell ranging from 1391 to 15133, CV = 58.62%; and K(d) from 2.5 to 98.6 nM, CV = 80.87%), reflects plasticity of the glucocorticoid system. The results pose the question of whether this compensatory mechanism observed in healthy human subjects persists in pathophysiological states associated with glucocorticoid hormone actions and suggest that tissue sensitivity to glucocorticoids could be better predicted by the sign and magnitude of the correlation between the two receptor equilibrium binding parameters than by each of them separately.     

黎族人的瘦体与脂肪质量指数

2014年11月在海南省五指山市5个黎族村寨测量了607例(男为308例,女为299例)黎族人体质量、身高等6项体成分指标值,计算了黎族人的体脂率(P_(bf))、瘦体质量(m_l)、脂肪质量(m_f)、瘦体质量指数(I_(lm))、脂肪质量指数(I_(fm))。研究发现,女性体脂率、脂肪质量、脂肪质量指数都明显大于男性,瘦体质量、瘦体质量指数均明显小于男性。随年龄增长,黎族人身高、瘦体质量逐渐减小,体脂率、脂肪质量、脂肪质量指数逐渐增大。受试者特征曲线显示身体质量指数、脂肪质量指数都可以适宜评价黎族人的体脂率,而且脂肪质量指数对体脂率的估算准确性比身体质量指数更高。这也提示脂肪质量指数是比身体质量指数评价肥胖更好的指标。