The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Anthropometric Characteristics of Elite Adolescent Competitive Swimmers

Densiometric determination of body composition and anthropometric assessment of somatotype and skeletal diameters were obtained on 39 male and 67 female Junior Olympic swimmers to determine the extent to which specific traits characterized these elite adolescent performers when compared to adult competitors or other adolescent athletes and non-athletes. Comparisons of the male and female Junior Olympic swimmers with respective samples of adult competitors revealed the younger groups having lower levels of lean body weight, in spite of similar skeletal dimensions. Similar comparisons of somatotype revealed equivalent or slightly less mesomorphic characteristics in the Junior Olympians. When compared to elite adolescent runners, the Junior Olympic swimmers of either sex displayed larger biacromial diameters, body weight, fat weight, and relative fat levels. Differences between Junior Olympic swimmers and adolescent non-athletes were also noted with the former group tending to be taller, broader in biacromial diameter, heavier in body weight and lean body weight, but with only the female swimmers displaying lower levels of fatness. These results indicate that particular anthropometric traits distinguish elite adolescent swimmers from older competitors, adolescent athletes in other sports, and non-athletic peers

Estimation of Body Density in Adolescent Athletes

National samples of 141 male and 133 female highly-trained adolescent athletes were studied to derive anthropometric-based equations predicting body density. Anthropometric measures included skinfold thicknesses at seven sites, circumferences at 14 sites, and diameters at nine sites. Criterion measures of body density were determined by underwater weighing with corrections for residual lung volume based on the oxygen dilution method. Variable selection procedures included factor analysis followed by forward-stepping regression and polynomial analysis.For both the male and female samples, two quadratic equations utilizing either the sum of three or seven skinfold measures were derived. Within the male sample, high validity coefficients (R = 0.81 — 0.82) and low standard errors (SEE = 0.0055 — 0.0056 g-ml_1) were shown with these equations. Similar results were demonstrated with the equations for females (R = 0.82 and SEE = 0.0060 g-ml~!). Cross-validation on independent samples of male (n = 66) and female (n = 46) adolescent athletes further confirmed these findings. In the cross-validation sample of males, predicted scores were highly correlated with actual body density (r = 0.86 — 0.87) and the total error of prediction ranged from 0.0057 to 0.0061 g-ml_1. Among the females, these values were r = 0.82 — 0.83 and total error = 0.0058 to 0.0063 g-ml-1. These results indicate that within reasonable limits of error, the sum of three or seven skinfolds may be used to make estimates of the body density of adolescent male or female athletes