The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies

Maternal plasma contains circulating cell-free DNA fragments originating from both the mother and the placenta. The proportion derived from the placenta is known as the fetal fraction. When measured between 10 and 20 gestational weeks, the average fetal fraction in the maternal plasma is 10% to 15% but can range from under 3% to over 30%. Screening performance using next-generation sequencing of circulating cell-free DNA is better with increasing fetal fraction and, generally, samples whose values are less than 3% or 4% are unsuitable. Three examples of the clinical impact of fetal fraction are discussed. First, the distribution of test results for Down syndrome pregnancies improves as fetal fraction increases, and this can be exploited in reporting patient results. Second, the strongest factor associated with fetal fraction is maternal weight; the false negative rate and rate of low fetal fractions are highest for women with high maternal weights. Third, in a mosaic, the degree of mosaicism will impact the performance of the test because it will reduce the effective fetal fraction. By understanding these aspects of the role of fetal fraction in maternal plasma DNA testing for aneuploidy, we can better appreciate the power and the limitations of this impressive new methodology. © 2013 John Wiley & Sons, Ltd.     

Assessment of the Applicability of Capsid-Integrity Assays for Detecting Infectious Norovirus Inactivated by Heat or UV Irradiation

Food and Environmental Virology - Human noroviruses are the leading cause of viral gastroenteritis. In the absence of a practical culture technique for routine analysis of infectious noroviruses,...     

Expanded carrier screening: What conditions should we screen for?

Carrier screening tests reproductive couples for their risk of having children affected by serious monogenic conditions. Carrier screening has historically been offered for certain conditions in high-risk populations. However, more recent evidence has shown that offering carrier screening to all patients, regardless of their ethnicity, more effectively and equitably identifies at-risk couples. Coupled with technology that enables screening for a nearly unlimited number of conditions, this expanded carrier screening (ECS) approach is now supported by professional society guidelines. Despite recent recommendations by the American College of Medical Genetics and Genomics to screen all patients who are pregnant or considering pregnancy for 113 conditions, questions remain about what conditions should be included on a core ECS panel. Here, we briefly review the history of carrier screening and guidelines on criteria for panel design. We then suggest which of these criteria are most critical, as well as thresholds to identify which conditions meet these criteria. Based on these interpretations, we recommend a core panel of 64 conditions that would identify the vast majority of at-risk couples. Widespread adoption of a core panel such as this would result in a marked improvement in the number of patients currently receiving comprehensive carrier screening.     

Preying on commercial fisheries and accumulating paralytic shellfish toxins: a dietary analysis of invasive Dosidicus gigas (Cephalopoda Ommastrephidae) stranded in Pacific Canada

In fall of 2009, several mass strandings of Humboldt squid (Dosidicus gigas) occurred on Vancouver Island (49°7′60N 125°54′0W). Morphological dissections coupled with DNA barcoding of stomach contents revealed Sardinops sagax (Pacific sardine) and Clupea pallasii (Pacific herring) as their primary prey. Plastic nurdles, fishing line, bull kelp, eelgrass, and a guillemot feather were also discovered. The primary prey, Pacific sardines and Pacific herring, are known to bioaccumulate paralytic shellfish toxins (PSTs); additionally, both PSTs and domoic acid (DA) have been implicated in other mass strandings. Therefore, stomach contents, and other tissues when possible, were tested for PSTs and DA. Testing revealed DA concentrations below regulatory guidance levels for human consumption, yet PSTs were well in excess. Though we cannot conclude that PSTs were the definitive cause of the strandings, our findings are the first report of PSTs in D. gigas.