Despite their clinical significance, characterization of balanced chromosomal abnormalities (BCAs) has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and revealed complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. This study proposes that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements, and provides insight into novel pathogenic mechanisms such as altered regulation due to changes in chromosome topology.

This paper examines health care utilization among indigenous immigrants from Oaxaca, Mexico, who have settled in a farmworker community in southern California. In 2016, two trained Spanish-Mixteco and Spanish-Zapoteco bi-lingual interviewers conducted in-depth interviews with 44 indigenous women residing in Oxnard, California on issues that affect health care utilization. Interviews were conducted in Mixteco, Zapoteco and Spanish and were coded to identify structural, cultural, and provider-related barriers to health care utilization. Five bi-lingual Spanish-Mixteco indigenous interpreters employed at local clinics were also interviewed. Many women reported lack of health insurance, inability to pay, language barriers, long waiting times, rushed encounters with providers, and seeking western medical care only after home remedies did not work. However, several women were able to access routine health care services, often with support from indigenous interpreters employed at clinics. Interviews with five interpreters found that they provided assistance with interpretation during medical encounters and appointment making. They also educated patients about upcoming exams, identified low-cost services and insurance programs available to patients, assisted with paperwork and occasionally educated physicians on behalf of their patients. In addition to addressing barriers to health care access our findings suggest the importance of identifying and leveraging community assets, such as indigenous navigators, when developing programs for such underserved communities. Our findings can inform best practice in settings that provide health care to indigenous populations and may also apply to settings that provide health care to other immigrant communities that have very limited familiarity and contact with western health care.

Type 2 diabetes mellitus (T2DM) genetic testing is undergoing clinical trials to measure the efficacy of genetic counseling for behavior-based risk reduction. The expectations patients bring to the testing process may play an important role in individual outcomes. We conducted a qualitative exploration of anticipated decision-making and expectations around T2DM genetic testing. Semi-structured interviews were completed with Mexican Americans (n = 34), non-Hispanic Black Americans (n = 39), and non-Hispanic White Americans (n = 39) at risk for T2DM. Transcripts were analyzed for themes. Most participants would accept T2DM genetic testing in order to motivate risk-reducing behaviors or apprise family members of their risk. Participants who would decline testing wished to avoid emotional distress or believed the test would not reveal new risk information. Non-Hispanic Whites and those with college education declined genetic testing more often than other groups. Those without college education were more likely to have testing expectations that were discordant with current science, such as conflating genetic testing with common ‘blood tests.’ Understanding expectations and decision-making factors around T2DM genetic testing will better prepare healthcare professionals to counsel their patients. This may lead to a higher efficacy of T2DM genetic testing and counseling.