Targeted suppression of gibberellin biosynthetic genes ZmGA20ox3 and ZmGA20ox5 produces a short stature maize ideotype.

Maize is one of the world's most widely cultivated crops. As future demands for maize will continue to rise, fields will face ever more frequent and extreme weather patterns that directly affect crop productivity. Development of environmentally resilient crops with improved standability in the field, like wheat and rice, was enabled by shifting the architecture of plants to a short stature ideotype. However, such architectural change has not been implemented in maize due to the unique interactions between gibberellin (GA) and floral morphology which limited the use of the same type of mutations as in rice and wheat. Here, we report the development of a short stature maize ideotype in commercial hybrid germplasm, which was generated by targeted suppression of the biosynthetic pathway for GA. To accomplish this, we utilized a dominant, miRNA-based construct expressed in a hemizygous state to selectively reduce expression of the ZmGA20ox3 and ZmGA20ox5 genes that control GA biosynthesis primarily in vegetative tissues. Suppression of both genes resulted in the reduction of GA levels leading to inhibition of cell elongation in internodal tissues, which reduced plant height. Expression of the miRNA did not alter GA levels in reproductive tissues, and thus, the reproductive potential of the plants remained unchanged. As a result, we developed a dominant, short-stature maize ideotype that is conducive for the commercial production of hybrid maize. We expect that the new maize ideotype would enable more efficient and more sustainable maize farming for a growing world population.

Assessing the barriers to cardiac care in carriers of Duchenne and Becker muscular dystrophy.

Duchenne and Becker muscular dystrophy (DBMD) are X-linked conditions causing progressive muscle weakness, muscle wasting, and cardiomyopathy in affected males. Two-thirds of cases of DBMD are inherited from a carrier female while one-third of cases occur sporadically. Women who are DBMD carriers typically do not manifest noticeable muscular symptoms. However, about 10% may develop cardiomyopathy while up to 60% are at risk for cardiac abnormalities including myocardial damage, fibrosis, and abnormalities detectable by echocardiogram and electrocardiogram (EKG). The American Academy of Pediatrics (AAP) recommends that carriers of DBMD receive a complete cardiac evaluation beginning at age 25-30 which includes an echocardiogram and EKG, with re-evaluation at least every 5 years. As many as 54.5% carriers may not be adhering to the AAP recommendations (Bogue et al., 2016). This study was conducted to define the perceived challenges carriers of DBMD face in obtaining cardiac care. A questionnaire was completed by 60 carriers of DBMD recruited through The Duchenne Registry to determine their current cardiac care practices. The majority of carriers surveyed (71.7%, 43/60) self-reported obtaining appropriate cardiac care while 28.3% (17/60) of carriers surveyed did not. Eleven semi-structured telephone interviews were conducted with a subset of those who completed the questionnaire. Individuals were eligible for telephone interview if they had not: (a) seen a cardiologist in the last 5 years, (b) had an echocardiogram in the last 5 years, or (c) had an EKG in the last 5 years. The primary theme identified from this cohort was a perceived lack of awareness among healthcare providers regarding cardiac risks in carriers (11/11). Increased awareness, health education regarding risks for carriers, and advocacy efforts are needed for healthcare providers and DBMD carriers in order to ensure that this entire population receives the cardiac care they need.

The Intrapsychic Psychological Binds of Poverty and Race: The Intersection of Mind and Milieu.

Race and poverty are poignant factors in how individuals and communities experience the world. The reality is that more people of color than White people live in poverty (Milner, 2013). How these inequalities intersect with the mind and environment is of compelling importance. The experiences of race and living in poverty are riddled with innumerable stressors and barriers, and as a result are subject to the experience of a range of mental health issues. Those that live the experience of trauma related to race and poverty suffer disproportionately from a host of hardships that contribute to psychological distress that can have a profound effect on mental health and serve as intrapsychic binds. These internalized weights require therapeutic supports to alleviate the internal oppressive circumstances by those that are immersed in the experience on a daily basis. This article explores the intersection of these psychological binds and their effect on human behavior.

The Global State of the Genetic Counseling Profession.

The profession of genetic counseling (also called genetic counselling in many countries) began nearly 50 years ago in the United States, and has grown internationally in the past 30 years. While there have been many papers describing the profession of genetic counseling in individual countries or regions, data remains incomplete and has been published in diverse journals with limited access. As a result of the 2016 Transnational Alliance of Genetic Counseling (TAGC) conference in Barcelona, Spain, and the 2017 World Congress of Genetic Counselling in the UK, we endeavor to describe as fully as possible the global state of genetic counseling as a profession. We estimate that in 2018 there are nearly 7000 genetic counselors with the profession established or developing in no less than 28 countries.

Prenatal genetic carrier screening in the genomic age.

The Society for Maternal-Fetal Medicine, American College of Obstetricians and Gynecologists (ACOG), and American College of Medical Genetics and Genomics (ACMG) held a workshop entitled "Prenatal Genetic Testing" on January 25, 2017 to address several questions arising from the increasing implementation of preconception and prenatal expanded carrier screening (ECS). ECS allows for identification of a greater number of genetic sequencing changes (not all of which cause disease) and simultaneous testing for an increased number of genetic conditions without limitation to specific ethnic groups. The workshop participants reached consensus on the following: ethnicity based testing cannot be completely abandoned in favor of panethnic ECS; the specific approach to screening should be a patient's choice and not driven solely by provider preference; organizations should work to develop a framework for vetting conditions that should be reported on ECS panels; compared with prenatal screening, preconception screening is ideal and, at this time, due to the costs and the need for timeliness associated with prenatal screening posttest counseling and testing, that when ECS is offered it should be presented as a preconception option; preconception and prenatal panels should be identical across the spectrum of patients, including those undergoing assisted reproduction; adult-onset conditions should not be included on ECS panels; partners should be offered next-generation sequencing to identify rare variants when the first partner screened is determined to be a carrier; re-screening in subsequent pregnancies is not indicated, despite the potential for expansion of carrier screening conditions and variants; and more education about ECS for providers and patients is necessary to implement prenatal carrier screening in a responsible way.

Prenatal detection of 10q22q23 duplications: dilemmas in phenotype prediction.

OBJECTIVES: The phenotype for 10q22q23 duplication is diverse, ranging from intellectual disability and dysmorphism to normal development. Interpreting the clinical significance of the duplication identified in this region is difficult, especially in the prenatal setting. This study aimed to characterize the prenatal findings associated with this submicroscopic imbalance and discuss the dilemmas in predicting the phenotype of 10q22q23 duplications. METHODS: This is a retrospective study of three cases of 10q22q23 duplications diagnosed prenatally by chromosomal microarray analysis. Detailed pregnancy outcome and pediatric follow-up were documented. RESULTS: The genotypic and phenotypic features of the reported cases were discussed. 10q22q23 duplications are associated with an unpredictable and variable phenotypic outcome. Despite there was no phenotype found to be shared by 50% of the duplication cases, congenital heart defects, hypotelorism, and developmental delays including speech and motor delay seem to be more common. CONCLUSIONS: The phenotype of 10q22q23 duplication is highly variable prenatally and postnatally. Identification of additional affected individuals with similar duplications is needed to provide further insights into the pathogenesis of this microduplication. © 2016 John Wiley & Sons, Ltd.

Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.

The Perinatal Quality Foundation and the American College of Medical Genetics and Genomics, in association with the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the National Society of Genetic Counselors, have collaborated to provide education for clinicians and laboratories regarding the use of expanded genetic carrier screening in reproductive medicine. This statement does not replace current screening guidelines, which are published by individual organizations to direct the practice of their constituents. As organizations develop practice guidelines for expanded carrier screening, further direction is likely. The current statement demonstrates an approach for health care providers and laboratories who wish to or who are currently offering expanded carrier screening to their patients.

The transnational alliance for genetic counseling: promoting international communication and collaboration.

The Transnational Alliance for Genetic Counseling seeks to promote communication and collaboration among genetic counselor educators, internationally. Connecting and building global relationships among colleagues also promotes the development of the genetic counseling profession. Genetic counselors everywhere can achieve deeper understanding of their work by seeking international perspectives.

Prenatal diagnosis of Down syndrome: a systematic review of termination rates (1995-2011).

OBJECTIVE: The objective of this study was to review the published literature on pregnancy termination following a prenatal diagnosis of Down syndrome in the United States. METHOD: A systematic search of US English-language articles (1995-2011) was conducted to identify primary research studies that reported data for pregnancies with definitive prenatal diagnosis of Down syndrome with subsequent pregnancy termination. Studies that provided indirect estimates of pregnancy termination, such as mathematical models, were excluded. The weighted mean termination rate was calculated across studies. RESULTS: Twenty-four studies were accepted. The weighted mean termination rate was 67% (range: 61%-93%) among seven population-based studies, 85% (range: 60%-90%) among nine hospital-based studies, and 50% (range: 0%-100%) among eight anomaly-based studies. Evidence suggests that termination rates have decreased in recent years. Termination rates also varied with maternal age, gestational age, and maternal race/ethnicity. CONCLUSION: This systematic review presents the largest synthesis of United States data on termination rates following a prenatal diagnosis of Down syndrome. Evidence suggests that termination rates are lower than noted in a previous review that was based on less contemporary studies and had an international focus. Heterogeneity across studies suggests that a summary termination rate may not be applicable to the entire US population.

Contemporary genetic counseling.

Genetic counseling is a specialty service integrally related to obstetrics and gynecology. This article discusses the genetic counseling resources available to the obstetrician gynecologist, including contact with referral centers near their practice and web-based resources for current genetic information. Indications for genetic counseling that incorporate new approaches and technologies are highlighted.

Declaración de consenso sobre el diagnóstico prenatal del síndrome de Down / No disponible

Recientemente se han aireado las preocupaciones mostradas por partede las organizaciones que abogan por la dignidad de las personas con síndrome deDown sobre el cribado y diagnóstico prenatal, particularmente en respuesta a los Boletinessobre Práctica nos. 77 y 88 emitidos por el American College of Obstetritians andGynecologists. El Programa de Consejo Genético de la Universidad de Carolina del Sur(PCG-UCS) decidió que había llegado la hora de convocar a representantes de las organizacionesimplicadas para discutir de forma abierta las percepciones y malentendidossobre las pruebas prenatales en cuanto se relacionan con el síndrome de Down,con el propósito de identificar áreas de consenso sobre las que se pueda seguir elaborando.El documento que acompaña es el resultado de dos días de conversaciones y untestimonio de lo que puede ocurrir cuando el objetivo es explorar un terreno comúnpara conseguir un bien superior(AU)

High-frequency ultrasound measurement for assessing post-thrombotic syndrome and monitoring compression therapy in chronic venous disease.

BACKGROUND: The purpose of this study was to validate high-frequency ultrasound (HFU) measurement of dermal thickness for quantification of edema in patients with different severities of chronic venous disease. METHODS: HFU measurements of dermal thickness were made with a 17-MHz probe (Philips iU22 Ultrasound scanner, Bothell, Wash) or a 20-MHz medium-focus probe (DermaScan-C, Cortex Technology, Denmark), 7.5 cm above the medial malleolus. For validation, 20 patients with venous leg ulcers who were not receiving compression therapy, 20 patients with previous deep vein thrombosis (DVT) and symptoms of post-thrombotic syndrome (PTS) without ulceration, and 31 age-matched healthy controls were measured on a single occasion. To investigate the effect of compression on dermal thickness, the leg ulcer patients from the validation study were treated with compression therapy for 7 weeks and measured after 1, 3, 5, and 7 weeks. The association between dermal thickness and the clinical (C) component of the CEAP classification was examined in a cross-sectional analysis of 157 patients with a confirmed history of DVT >or=3 years ago. RESULTS: Dermal thickness in patients with venous leg ulcers before compression therapy (median, 2.56 mm; interquartile range [IQR], 2.31-2.82 mm) was significantly greater (P = .002) than that in patients with symptoms of PTS without ulceration (median, 2.16 mm; IQR, 1.90-2.36 mm). Dermal thickness in both groups was significantly greater (P < .0001) than the control group (median, 1.34 mm; IQR, 1.29-1.44 mm). Compression therapy caused a steady and significant decrease in dermal thickness during the first 5 weeks until normal control levels were achieved. Dermal thickness increased with increasing CEAP category. In 121 patients with a positive diagnosis of DVT >or=3 years ago from Radiology Department records, a hypothetical test cutoff of 1.985 mm for the prediction of severe PTS noted as C(4b), C(5), and C(6) (lipodermatosclerosis or leg ulceration) had a positive predictive value of 46.9% and a negative predictive value of 90.3%. CONCLUSION: HFU measurement of dermal thickness enables the monitoring of edema reduction by compression therapy. A prospective study is required to determine the temporal dynamics of dermal thickness changes after DVT and the relationship to the development of PTS. This test has the potential to be beneficial in the follow-up of patients after a DVT and provide clinical evidence for using graduated elastic compression stockings to control edema and prevent the development of more advanced skin changes.

Rapid one-step recombinational cloning.

As an increasing number of genes and open reading frames of unknown function are discovered, expression of the encoded proteins is critical toward establishing function. Accordingly, there is an increased need for highly efficient, high-fidelity methods for directional cloning. Among the available methods, site-specific recombination-based cloning techniques, which eliminate the use of restriction endonucleases and ligase, have been widely used for high-throughput (HTP) procedures. We have developed a recombination cloning method, which uses truncated recombination sites to clone PCR products directly into destination/expression vectors, thereby bypassing the requirement for first producing an entry clone. Cloning efficiencies in excess of 80% are obtained providing a highly efficient method for directional HTP cloning.

Attitudes of families affected by adrenoleukodystrophy toward prenatal diagnosis, presymptomatic and carrier testing, and newborn screening.

Families affected by adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN) were surveyed to elicit attitudes toward prenatal, presymptomatic and carrier testing, and newborn screening in order to determine the level of support that these families have for current and future genetic testing protocols. Identifying attitudes toward genetic testing, including newborn screening, is especially important because of new data regarding therapeutic options and the possible addition of ALD to newborn screening regimens. The Kennedy Krieger Institute (KKI) database identified 327 prospective participants. Families that were willing to participate in the study received an anonymous questionnaire for completion. Frequencies were generated using SPSS software for Windows. Questionnaires were returned from 128 families for a response rate of 39%. Sons who were at risk for inheriting the ALD gene would be tested by 93% of respondents, and 89.3% would ideally have this testing performed prenatally or in the newborn period. Eighty-nine percent would test an at-risk daughter and 51.2% would ideally have this testing performed prenatally or shortly after birth. ALD newborn screening for males and females was supported by 90% of respondents. If newborn screening for ALD/AMN commences, or there is a new diagnosis of ALD, genetic professionals need to be prepared to have extensive conversations with families regarding the benefits and limitations of current therapeutic and genetic testing options.

Lost in transition: challenges in the expanding field of adult genetics.

It is increasingly clear that medical genetics has broad relevance in adult clinical medicine. More adult patients with genetic conditions are being recognized, genetic testing for adult-onset genetic conditions is expanding, and children with genetic conditions are now more likely to survive to adulthood. While the number of patients who could benefit from medical genetic services increases, adult care providers are less well educated about clinical genetics and are not sufficiently prepared to meet the growing needs of this population. Genetics professionals may also be ill-suited for this challenge, since geneticists and genetic counselors have traditionally had greater experience in pediatric and prenatal settings. Communication between primary care physicians who treat adults and the genetics community is currently suboptimal and the identification and subsequent referral of adult patients for genetic services need improvement. Finally, published guidelines that address how to deliver genetic services to adult patients are unavailable for many genetic conditions. In this article we address the challenges of transitioning genetics services from traditional, and largely pediatric-based models to paradigms that can best address the needs of adult patients with genetic conditions. Potential solutions and the practicality of implementation of a team-based approach to adult genetic medicine, including the application of genetic counseling, are also discussed.

Constitutional mosaic trisomy 21 and azoospermia: a case report.

Constitutional full trisomy 21 is a common disorder in which abnormal spermatogenesis has been previously described. However, constitutional mosaic trisomy 21 in an otherwise normal but infertile male has not been explored. We report a case with low level mosaic trisomy 21 in a non-syndrome but azoospermic patient. We also propose that the patient's azoospermia may be related to the constitutional mosaic trisomy 21 and thus resulting in a late onset of testicular failure.