A Screening Test for in a Large United States Patient Cohort Identifies Broader Risk of Carbamazepine-Induced Adverse Events.

is strongly associated with life-threatening severe skin hypersensitivity reactions in patients treated with carbamazepine (CBZ) and structurally related medications. FDA-approved labeling recommends screening before CBZ therapy in patients of Asian ancestry. In this study, we aimed to (a) identify a direct method for screening , and (b) evaluate prevalence in a large cohort of United States patients.

Frequency of Alleles Including Structural Variants in the United States.

The gene encodes an enzyme important in the metabolism of many commonly used medications. Variation in is associated with inter-individual differences in medication response, and genetic testing is used to optimize medication therapy. This report describes a retrospective study of allele frequencies in a large population of 104,509 de-identified patient samples across all regions of the United States (US).

The impact of direct-to-consumer personal genomic testing on perceived risk of breast, prostate, colorectal, and lung cancer: findings from the PGen study.

Background: Direct access to genomic information has the potential to transform cancer risk counseling. We measured the impact of direct-to-consumer genomic risk information on changes to perceived risk (ΔPR) of breast, prostate, colorectal and lung cancer among personal genomic testing (PGT) customers. We hypothesized that ΔPR would reflect directionality of risk estimates, attenuate with time, and be modified by participant characteristics.

Explaining, not just predicting, drives interest in personal genomics.

Background: There is a widespread assumption that risk prediction is the major driver of customer interest in personal genomic testing (PGT). However, some customers may also be motivated by finding out whether their existing diseases have a genetic etiology. We evaluated the impact of an existing medical diagnosis on customer interest in condition-specific results from PGT.

Design, methods, and participant characteristics of the Impact of Personal Genomics (PGen) Study, a prospective cohort study of direct-to-consumer personal genomic testing customers.

Designed in collaboration with 23andMe and Pathway Genomics, the Impact of Personal Genomics (PGen) Study serves as a model for academic-industry partnership and provides a longitudinal dataset for studying psychosocial, behavioral, and health outcomes related to direct-to-consumer personal genomic testing (PGT). Web-based surveys administered at three time points, and linked to individual-level PGT results, provide data on 1,464 PGT customers, of which 71% completed each follow-up survey and 64% completed all three surveys. The cohort includes 15.

Navigating a research partnership between academia and industry to assess the impact of personalized genetic testing.

Purpose: To describe the process of structuring a partnership between academic researchers and two personalized genetic testing companies that would manage conflicts of interest while allowing researchers to study the impact of this nascent industry.

Methods: We developed a transparent process of ongoing communication about the interests of all research partners to address challenges in establishing study goals, survey development, data collection, analysis, and manuscript preparation. Using the existing literature on conflicts of interest and our experience, we created a checklist for academic and industry researchers seeking to structure research partnerships.

Retinoic acid regulation of the Mesp-Ripply feedback loop during vertebrate segmental patterning.

The Mesp bHLH genes play a conserved role during segmental patterning of the mesoderm in the vertebrate embryo by specifying segmental boundaries and anteroposterior (A-P) segmental polarity. Here we use a xenotransgenic approach to compare the transcriptional enhancers that drive expression of the Mesp genes within segments of the presomitic mesoderm (PSM) of different vertebrate species. We find that the genomic sequences upstream of the mespb gene in the pufferfish Takifugu rubripes (Tr-mespb) are able to drive segmental expression in transgenic Xenopus embryos while those from the Xenopus laevis mespb (Xl-mespb) gene drive segmental expression in transgenic zebrafish.

Noelins modulate the timing of neuronal differentiation during development.

Noelins comprise a family of extracellular proteins with proposed roles in neural and neural crest development. Here, we show that a previously uncharacterized family member, Noelin-4, functions to maintain neural precursors in an undifferentiated state and biases ectoderm toward a neural fate. We show that Noelin-4 is induced by the neurogenic genes X-ngnr-1 and XNeuroD.

Regulation of segmental patterning by retinoic acid signaling during Xenopus somitogenesis.

Somites, the segmented building blocks of the vertebrate embryo, arise one by one in a patterning process that passes wavelike along the anteroposterior axis of the presomitic mesoderm (PSM). We have studied this process in Xenopus embryos by analyzing the expression of the bHLH gene, Thylacine1, which is turned on in the PSM as cells mature and segment, in a pattern that marks both segment boundaries and polarity. Here, we show that this segmental gene expression involves a PSM enhancer that is regulated by retinoic acid (RA) signaling at two levels.

Neural expression of mouse Noelin-1/2 and comparison with other vertebrates.

Noelins are secreted glycoproteins with important developmental functions in frogs and birds. Here, we present the expression pattern of the mouse homolog of Noelin-1/2 at E8-10 of development and compare this pattern to other vertebrates. Expression was observed in the neural plate and neural crest, as well as in the cranial ganglia.