Within-day baseline variation in salivary biomarkers in healthy men

Saliva is an easily accessible sample and offers practical and noninvasive biomarker solutions as an alternative to blood and urine-based diagnostics. Saliva contains a plethora of biomolecules such as nucleic acids, hormones, proteins, and electrolytes. On the other hand, little is known on the extent to which the biomolecules in saliva vary over time within a given person. This baseline information is crucial for future development of robust saliva-based diagnostics. We have collected unstimulated whole mouth saliva from 20 healthy young men at four times during the day, including before and after a meal. We measured the salivary cortisol, testosterone, C-reactive protein (CRP), stability of genomic DNA (gDNA) and DNA methylation levels of APC, P16, and PCQAP in these samples. We found that the salivary CRP, DNA methylation, and CD44 gDNA levels did not vary significantly across four time points (p > 0.05) while the salivary cortisol and testosterone levels significantly varied from the morning collection to the afternoon collection (p < 0.05). Furthermore, salivary cortisol levels were significantly affected by eating (p < 0.05). Our study offers a within-person baseline temporal assessment of several clinically relevant biomolecules and diagnostics, and suggests that salivary cortisol and testosterone levels vary over time in a given day whereas CRP and DNA methylation of tumor suppressor genes and CD44 amplification are stable throughout the day. Future research and clinical applications of salivary biomarkers and diagnostics should take into consideration their temporal variations

Exceptional Complex Chromosomal Rearrangements in Three Generations

We report an exceptional complex chromosomal rearrangement (CCR) found in three individuals in a family that involves 4 chromosomes with 5 breakpoints. The CCR was ascertained in a phenotypically abnormal newborn with additional chromosomal material on the short arm of chromosome 4. Maternal karyotyping indicated that the mother carried an apparently balanced CCR involving chromosomes 4, 6, 11, and 18. Maternal transmission of the derivative chromosome 4 resulted in partial trisomy for chromosomes 6q and 18q and a partial monosomy of chromosome 4p in the proband. Further family studies found that the maternal grandmother carried the same apparently balanced CCR as the proband’s mother, which was confirmed using the whole chromosome painting (WCP) FISH. High resolution whole genome microarray analysis of DNA from the proband’s mother found no evidence for copy number imbalance in the vicinity of the CCR translocation breakpoints, or elsewhere in the genome, providing evidence that the mother’s and grandmother’s CCRs were balanced at a molecular level. This structural rearrangement can be categorized as an exceptional CCR due to its complexity and is a rare example of an exceptional CCR being transmitted in balanced and/or unbalanced form across three generations