Carrier Screening is a Deficient Strategy for Determining Sperm Donor Eligibility and Reducing Risk of Disease in Recipient Children.

AIMS: DNA-based carrier screening is a standard component of donor eligibility protocols practiced by U.S. sperm banks. Applicants who test positive for carrying a recessive disease mutation are typically disqualified. The aim of our study was to examine the utility of a range of screening panels adopted by the industry and the effectiveness of the screening paradigm in reducing a future child's risk of inheriting disease. METHODS: A cohort of 27 donor applicants, who tested negative on an initial cystic fibrosis carrier test, was further screened with three expanded commercial carrier testing panels. These results were then compared to a systematic analysis of the applicants' DNA using next-generation sequencing (NGS) data. RESULTS: The carrier panels detected serious pediatric disease mutations in one, four, or six donor applicants. Because each panel screens distinct regions of the genome, no single donor was uniformly identified as carrier positive by all three panels. In contrast, systematic NGS analysis identified all donors as carriers of one or more mutations associated with severe monogenic pediatric disease. These included 30 variants classified as "pathogenic" based on clinical observation and 66 with a high likelihood of causing gene dysfunction. CONCLUSION: Despite tremendous advances in variant identification, understanding, and analysis, the vast majority of disease-causing mutation combinations remain undetected by commercial carrier screening panels, which cover a narrow, and often distinct, subset of genes and mutations. The biological reality is that all donors and recipients carry serious recessive disease mutations. This challenges the utility of any screening protocol that anchors donor eligibility to carrier status. A more effective approach to reducing recessive disease risk would consider joint comprehensive analysis of both donor and recipient disease mutations. This type of high-resolution recessive disease risk analysis is now available and affordable, but industry practice must be modified to incorporate its use.

Stop holding yourself back.

After working with hundreds of leaders in a wide variety of organizations and in countries all over the globe, the authors found one very clear pattern: When it comes to meeting their leadership potential, many people unintentionally get in their own way. Five barriers in particular tend to keep promising managers from becoming exceptional leaders: People overemphasize personal goals, protect their public image, turn their competitors into two-dimensional enemies, go it alone instead of soliciting support and advice, and wait for permission to lead. Troy, a customer service manager, endangered his job and his company's reputation by focusing on protecting his position, not helping his team; when a trusted friend advised him to change his behavior, the results were striking. Anita's insistence on sticking to the tough personal she'd created for herself caused her to ignore the more intuitive part of the leadership equation, with disastrous results--until she let go of the need to appear invulnerable and reached out to another manager. Jon, a personal trainer who had virtually no experience with either youth development programs or urban life, opened a highly successful gym for inner-city kids at risk; he refused to be daunted by his lack of expertise and decided to simply "go for it." As these and other examples from the authors' research demonstrate, being a leader means making an active decision to lead. Only then will the workforce--and society--benefit from the enormous amount of talent currently sitting on the bench.