Familial communication and cascade testing following elective genomic testing.

Familial communication of results and cascade genetic testing (CGT) can extend the benefits of genetic screening beyond the patient to their at-risk relatives. While an increasing number of health systems are offering genetic screening as an elective clinical service, data are limited about how often results are shared and how often results lead to CGT. From 2018 to 2022, the Sanford Health system offered the Sanford Chip, an elective genomic test that included screening for medically actionable predispositions for disease recommended by the American College of Medical Genetics and Genomics for secondary findings disclosure, to its adult primary care patients. We analyzed patient-reported data about familial sharing of results and CGT among patients who received Sanford Chip results at least 1 year previously. Among the patients identified with medically actionable predispositions, 94.6% (53/56) reported disclosing their result to at least one family member, compared with 46.7% (423/906) of patients with uninformative findings (p < 0.001). Of the patients with actionable predispositions, 52.2% (12/23) with a monogenic disease risk and 12.1% (4/33) with a carrier status reported that their relatives underwent CGT. Results suggest that while the identification of monogenic risk during elective genomic testing motivates CGT in many at-risk relatives, there remain untested at-risk relatives who may benefit from future CGT. Findings identify an area that may benefit from increased genetic counseling and the development of tools and resources to encourage CGT for family members.

The degree of abdominal imaging (AI) subspecialization of the reviewing radiologist significantly impacts the number of clinically relevant and incidental discrepancies identified during peer review of emergency after-hours body CT studies.

PURPOSE: To evaluate if and to what extent the degree of subspecialization in abdominal imaging (AI) affects rates of discrepancies identified on review of body CT studies initially interpreted by board-certified radiologists not specialized in AI. METHOD AND MATERIALS: AI division radiologists at one academic medical center were classified as primary or secondary members of the division based on whether they perform more or less than 50% of their clinical duties in AI. Primary AI division radiologists were further subdivided based on whether or not they focus their clinical duties almost exclusively in AI. All AI radiologists performed subspecialty review of all after-hours body CT studies initially interpreted by any non-division radiologist. The discrepancies identified in the subspecialty review of consecutive after-hours body CT scans performed between 7/1/10 and 12/31/10 were analyzed and placed into one of three categories: (1) discrepancies that potentially affect patient care ("clinically relevant discrepancies", or CRD); (2) discrepancies that would not affect patient care ("incidental discrepancies", or ID); and (3) other types of comments. Rates of CRD and ID detection were compared between subgroups of Abdominal Imaging Division radiologists divided by the degree of subspecialization. RESULTS: 1303 studies met the inclusion criteria. Of 742 cases reviewed by primary members of the AI division, 33 (4.4%) had CRD and 78 (10.5%) had ID. Of 561 cases reviewed by secondary members of the AI division, 11 (2.0%) had CRD and 36 (6.5%) had ID. The differences between the groups for both types of discrepancies were statistically significant (p = 0.01). When primary members of the AI division were further subdivided based on extent of clinical focus on abdominal imaging, rates of CRD and ID detection were higher for the subgroup with more clinical focus on abdominal imaging. CONCLUSION: The degree of AI subspecialization affects the rate of clinically relevant and ID identified in body CT interpretations initially rendered by board certified but non-abdominal imaging subspecialized radiologists.

Genomic regions influencing gene expression of the HMW glutenins in wheat.

Bread wheat (Triticum aestivum L.) produces glutenin storage proteins in the endosperm. The HMW glutenins confer distinct viscoelastic properties to bread dough. The genetics of HMW glutenin proteins have been extensively studied, and information has accumulated about individual subunits, chromosomal locations and DNA sequences, but little is known about the regulators of the HMW glutenins. This investigation addressed the question of glutenin regulators. Expression of the glutenins was analyzed using QRT-PCR in ditelosomic (dt) Chinese Spring (CS) lines. Primers were designed for each of 4 CS glutenin genes and a control, non-storage protein endosperm-specific gene Agp-L (ADP-glucose pyrophosphorylase). Each line represents CS wheat, lacking one chromosome arm. The effect of a missing arm could feasibly cause an increase, decrease or no change in expression. For each HMW glutenin, results indicated there were, on average, 8 chromosome arms with an up-regulatory effect and only one instance of a down-regulatory effect. There were significant correlations between orthologous and paralogous HMW glutenins for effects of chromosome groups B and D. Some or all the glutenin alleles shared regulatory loci on chromosome arms 2BS, 7BS, 4DS, 5DS and 6DS, and Agp-L shared regulatory loci with glutenins on arms 7AS, 7BS, 2DS, 3DS, 4DS and 5DS. These results suggest a few chromosome arms contain putative regulatory genes affecting the expression of conserved cis elements of 4 HMW glutenin and Agp-L genes in CS. Regulation by common genes implies the regulators have diverged little from the common wheat ancestor, and furthermore, some regulation may be shared by endosperm-specific-genes. Significant common regulators have practical implications.