Enhancing Equity in Genomics: Incorporating Measures of Structural Racism, Discrimination, and Social Determinants of Health.

The everyday harms of structural racism and discrimination, perpetuated through institutions, laws, policies, and practices, constitute social determinants of health, but measures that account for their debilitating effects are largely missing in genetic studies of complex diseases. Drawing on insights from the social sciences and public health, we propose critical methodologies for incorporating tools that measure structural racism and discrimination within genetic analyses. We illustrate how including these measures may strengthen the accuracy and utility of findings for diverse communities, clarify elusive relationships between genetics and environment in a racialized society, and support greater equity within genomics and precision health research.

Clinicians' perspectives on race-specific guidelines for hypertensive treatment.

Despite the general consensus that there is no biological basis to race, racial categorization is still used by clinicians to guide diagnosis and treatment plans for certain diseases. In medicine, race is commonly used as a rough proxy for unmeasured social, environmental, and genetic factors. The American College of Cardiology's Eighth Joint National Committee's (JNC 8) guidelines for the treatment of hypertension provide race-specific medication recommendations for Black versus non-Black patients, without strong evidence for race-specific physiological differences in drug response.

Compassion and equity-focused clinical genomics training for health professional learners.

There remains an urgent need for expanded genomics training in undergraduate medical education, especially as genetic and genomic assessments become increasingly important in primary care and routine clinical practice across specialties. Physician trainees continue to report feeling poorly prepared to provide effective consultation or interpretation of genomic test results. Here we report on the development, pilot implementation, and evaluation of an elective offering for pre-clinical medical students called the Sanford Precision Health Scholars Immersive Learning Experience (PHS), which was designed leveraging genetic counseling expertise as one means to address this need.

Compassion as a tool for allyship and anti-racism.

Racist systems, policies, and institutions subvert the quality of life for minoritized individuals and groups, across all indicators, from education and employment, to health, to community safety. Reforms to address systemic racism may be accelerated with greater support from allies who identify with the dominant groups that derive advantage from such systems. Although enhancing empathy and compassion for impacted individuals and groups may foster greater allyship with and support of minoritized communities, little work to date has assessed the relationships among compassion, empathy, and allyship.

Variations on a Chip: Technologies of Difference in Human Genetics Research.

In this article we examine the history of the production of microarray technologies and their role in constructing and operationalizing views of human genetic difference in contemporary genomics. Rather than the "turn to difference" emerging as a post-Human Genome Project (HGP) phenomenon, interest in individual and group differences was a central, motivating concept in human genetics throughout the twentieth century. This interest was entwined with efforts to develop polymorphic "genetic markers" for studying human traits and diseases.

The Operon Regulates the Timing of Sporulation during Myxococcus xanthus Development.

undergoes multicellular development when starved. Thousands of rod-shaped cells coordinate their movements and aggregate into mounds in which cells differentiate into spores. Mutations in the operon impair development.

devI is an evolutionarily young negative regulator of Myxococcus xanthus development.

Unlabelled: During starvation-induced development of Myxococcus xanthus, thousands of rod-shaped cells form mounds in which they differentiate into spores. The dev locus includes eight genes followed by clustered regularly interspaced short palindromic repeats (CRISPRs), comprising a CRISPR-Cas system (Cas stands for CRISPR associated) typically involved in RNA interference. Mutations in devS or devR of a lab reference strain permit mound formation but impair sporulation.

Nutrient-regulated proteolysis of MrpC halts expression of genes important for commitment to sporulation during Myxococcus xanthus development.

Starved Myxococcus xanthus cells glide to aggregation centers and form fruiting bodies in which rod-shaped cells differentiate into ovoid spores. Commitment to development was investigated by adding nutrients at specific times after starvation and determining whether development halted or proceeded. At 24 h poststarvation, some rod-shaped cells were committed to subsequent shape change and to becoming sonication-resistant spores, but nutrients caused partial disaggregation of fruiting bodies.

The RGSGR amino acid motif of the intercellular signalling protein, HetN, is required for patterning of heterocysts in Anabaena sp. strain PCC 7120.

Nitrogen-fixing heterocysts are arranged in a periodic pattern on filaments of the cyanobacterium Anabaena sp. strain PCC 7120 under conditions of limiting combined nitrogen. Patterning requires two inhibitors of heterocyst differentiation, PatS and HetN, which work at different stages of differentiation by laterally suppressing levels of an activator of differentiation, HetR, in cells adjacent to source cells.

Different differences: the use of 'genetic ancestry' versus race in biomedical human genetic research.

This article presents findings from our ethnographic research on biomedical scientists' studies of human genetic variation and common complex disease. We examine the socio-material work involved in genome-wide association studies (GWAS) and discuss whether, how, and when notions of race and ethnicity are or are not used. We analyze how researchers produce simultaneously different kinds of populations and population differences.

Temporal and spatial regulation of the four transcription start sites of hetR from Anabaena sp. strain PCC 7120.

The filamentous cyanobacterium Anabaena sp. strain PCC 7120 forms nitrogen-fixing heterocysts in a periodic pattern in response to combined-nitrogen limitation in the environment. The master regulator of heterocyst differentiation, HetR, is necessary for both pattern formation and commitment of approximately every 10th cell of a filament to differentiation into a heterocyst.

Race, genetics, and disease: questions of evidence, matters of consequence.

This special issue of Studies of Science highlights ongoing debates concerning race, genomics, and disease. Some of the papers examine the production of disease etiology research, pharmaceutical drug response, or DNA genealogy tests, while others analyze institutional consequences and challenges arising from contemporary biomedicine, such as medical education and recruiting subjects for clinical research. In this introduction, we outline major issues that provide background and foreground for the specific studies that follow, and end with a brief description of the papers.

FraG is necessary for filament integrity and heterocyst maturation in the cyanobacterium Anabaena sp. strain PCC 7120.

Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that differentiates nitrogen-fixing heterocysts when fixed nitrogen becomes growth limiting in the medium. The gene alr2338 (designated fraG herein), located immediately upstream of the master regulator of differentiation hetR, was identified in a genetic screen for mutants unable to grow diazotrophically.

A diverse and evolutionarily fluid set of microRNAs in Arabidopsis thaliana.

To better understand the diversity of small silencing RNAs expressed in plants, we employed high-throughput pyrosequencing to obtain 887,000 reads corresponding to Arabidopsis thaliana small RNAs. They represented 340,000 unique sequences, a substantially greater diversity than previously obtained in any species. Most of the small RNAs had the properties of heterochromatic small interfering RNAs (siRNAs) associated with DNA silencing in that they were preferentially 24 nucleotides long and mapped to intergenic regions.

A two-hit trigger for siRNA biogenesis in plants.

In Arabidopsis, microRNA-directed cleavage can define one end of RNAs that then generate phased siRNAs. However, most miRNA-targeted RNAs do not spawn siRNAs, suggesting the existence of additional determinants within those that do. We find that in moss, phased siRNAs arise from regions flanked by dual miR390 cleavage sites.

Endogenous trans-acting siRNAs regulate the accumulation of Arabidopsis mRNAs.

Here we describe a set of endogenous short interfering RNAs (siRNAs) in Arabidopsis, some of which direct the cleavage of endogenous mRNAs. These siRNAs correspond to both sense and antisense strands of a noncoding RNA (At2g27400) that apparently is converted to double-stranded RNA and then processed in 21 nt increments. These siRNAs differ from previously described regulatory small RNAs in two respects.