Novel COCH mutation in a family with autosomal dominant late onset sensorineural hearing impairment and tinnitus

This report describes a three generation family with late onset bilateral sensorineural hearing impairment (BLSNHI) and tinnitus in which a novel mutation in the COCH gene was identified after a genome-wide linkage approach. The COCH gene is one of the few genes clinically examined when investigating the etiology of autosomal dominant late onset hearing impairment. Initially mutations in the COCH gene were only reported in exons 4 and 5, coding for the LCCL protein domain. More recently, additional mutations have been identified in exon 12, the only mutations identified outside of the LCCL domain. Currently clinical genetic testing for the COCH gene primarily focuses on identifying mutations in these three exons. In this study, we identify a novel mutation in the COCH gene in exon 11, which, like the exon 12 mutations, falls within the vWFA2 protein domain. This finding reinforces the need for clinical genetic screening of the COCH gene to be expanded beyond the current limited exon screening, as there is now more evidence to support that mutations in other areas of this gene are also causative of a similar form of late onset BLSNHI.     

Legacy genetics of Arachis cardenasii in the peanut crop shows the profound benefits of international seed exchange

The narrow genetics of most crops is a fundamental vulnerability to food security. This makes wild crop relatives a strategic resource of genetic diversity that can be used for crop improvement and adaptation to new agricultural challenges. Here, we uncover the contribution of one wild species accession, Arachis cardenasii GKP 10017, to the peanut crop (Arachis hypogaea) that was initiated by complex hybridizations in the 1960s and propagated by international seed exchange. However, until this study, the global scale of the dispersal of genetic contributions from this wild accession had been obscured by the multiple germplasm transfers, breeding cycles, and unrecorded genetic mixing between lineages that had occurred over the years. By genetic analysis and pedigree research, we identified A. cardenasii–enhanced, disease-resistant cultivars in Africa, Asia, Oceania, and the Americas. These cultivars provide widespread improved food security and environmental and economic benefits. This study emphasizes the importance of wild species and collaborative networks of international expertise for crop improvement. However, it also highlights the consequences of the implementation of a patchwork of restrictive national laws and sea changes in attitudes regarding germplasm that followed in the wake of the Convention on Biological Diversity. Today, the botanical collections and multiple seed exchanges which enable benefits such as those revealed by this study are drastically reduced. The research reported here underscores the vital importance of ready access to germplasm in ensuring long-term world food security.

Globally, most of humanity’s food is produced by only a few crop species, most of which have low genetic diversity (1–4). This presents a fundamental limitation to genetic improvement of crops and a key vulnerability for food security. Wild crop relatives have been used as a strategic source of diversity for plant breeders (4, 5). However, the agronomically unadapted phenotypes of wild species have hampered their use. For peanut (Arachis hypogaea L.), a crop with an exceptionally narrow genetic base (6, 7), the incorporation of wild relatives into breeding programs is further impeded by barriers in sexual compatibility between the tetraploid crop and its almost exclusively diploid wild relatives (8–10). This ploidy difference arose 5,000 to 10,000 y ago with the formation of the tetraploid species, via the hybridization and spontaneous polyploidization of the diploid “A” genome species, Arachis duranensis Krapov. & W.C. Greg. and the “B” genome species, Arachis ipaënsis Krapov. & W.C. Greg. The resultant tetraploid diversified into many peanut (A. hypogaea) landraces and varieties through artificial selection during cultivation. Peanut maintains almost-complete sets of chromosomes from the two ancestral diploid species thus having a genome almost entirely of “AABB” structure, a type of polyploid termed a segmental allotetraploid (2n = 4x = 40 chromosomes; genome size of ∼2.7 Gb; 6, 11, 12).Despite the difficulties presented by the ploidy barrier, considerable effort was invested during the 1960s in complex hybridizations between peanut and a diploid “A” genome wild species accession from Bolivia, Arachis cardenasii Krapov. & W.C. Greg. GKP 10017 [PI (Plant Introduction) 262141]. Interest in this accession had been stimulated by its identification as a source of very strong pest and disease resistance (13). Using two different hybridization schemes, two different research groups obtained fertile progeny which entered into breeding programs (see Results for more details). However, over time, the subsequent dispersal and development of the resultant germplasm, with multiple seed transfers, identification code reassignments, breeding cycles, and unrecorded mixing of lineages, left the actual genetic contribution of the wild species mostly forgotten, unrecorded, or undefined.Here, we reveal the previously unknown scale of the genetic influence of A. cardenasii GKP 10017 as a donor of pest and disease resistances to the world’s peanut crop. This study involved the sequencing and assembly of the genome of this wild species accession and genetic analysis and pedigree research of diverse peanut lines from around the world. Peanuts with genetic contributions from A. cardenasii were identified on every populated continent and in 30 countries. The cultivars provided improved food security for subsistence farmers and environmental and economic benefits.     

Have men been overlooked? A comparison of young men and women's experiences of chemotherapy‐induced alopecia

Objective: The objective of this study is to compare men and women's accounts of chemotherapy‐induced alopecia. Design: Secondary analysis of narrative interview data. Participants: Thirty‐seven people aged 18–38 years, including 11 men and 8 women who had experienced hair loss, interviewed between 2000 and 2005. Setting: Participants were recruited throughout the United Kingdom. Results: Hair loss made many men and women acutely aware of their vulnerability and visibility as a ‘cancer patient’. Both men and women described a sense of strangeness or shock when they lost their hair and experienced various negative reactions when people assumed their hairless appearance was a lifestyle choice. The most striking contrast in men's and women's accounts was that women spoke solely of the loss of hair from the head and face above the eye line, and men spoke about losing hair from wider body surfaces. Only women mentioned being encouraged by others to disguise or to prevent hair loss. The results are discussed in relation to gendered assumptions about the distribution of body hair. Conclusions: Contrary to prevailing assumptions, both women and men described negative (and often similar) feelings about hair loss. Understanding these experiences can help professionals better equip their patients to deal with this aspect of their treatment. Copyright © 2007 John Wiley & Sons, Ltd.     

Maternal Obesity Induced by Diet in Rats Permanently Influences Central Processes Regulating Food Intake in Offspring

Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb) rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin mRNA expression in their abdominal white adipose tissue. At postnatal Day 30, before the onset of hyperphagia in these animals, serum leptin is normal, but leptin-induced appetite suppression and phosphorylation of STAT3 in the arcuate nucleus (ARC) are attenuated; the level of AgRP-immunoreactivity in the hypothalamic paraventricular nucleus (PVH), which derives from neurones in the ARC and is developmentally dependent on leptin, is also diminished. We hypothesise that prolonged release of abnormally high levels of leptin by neonatal OffOb rats leads to leptin resistance and permanently affects hypothalamic functions involving the ARC and PVH. Such effects may underlie the developmental programming of hyperphagia and obesity in these rats.     

Kidney Transplant-Associated Viral Infection Rates and Outcomes in a Single-Centre Cohort

Background: Opportunistic infections remain a significant cause of morbidity and mortality after kidney transplantation. This retrospective cohort study aimed to assess the incidence and predictors of post-transplant DNA virus infections (CMV, EBV, BKV and JCV infections) in kidney transplant recipients (KTR) at a single tertiary centre and evaluate their impact on graft outcomes. Methods: KTR transplanted between 2000 and 2021 were evaluated. Multivariate logistic regression analysis and Cox proportional hazard analyses were used to identify factors associated with DNA virus infections and their impact on allograft outcomes respectively. A sub-analysis of individual viral infections was also conducted to describe the pattern, timing, interventions, and outcomes of individual infections. Results: Data from 962 recipients were evaluated (Mean age 47.3 ± 15 years, 62% male, 81% white). 30% of recipients (288/962) had infection(s) by one or more of the DNA viruses. Individually, CMV, EBV, BKV and JCV viruses were diagnosed in 13.8%. 11.3%, 8.9% and 4.4% of recipients respectively. Factors associated with increased risk of post-transplant DNA virus infection included recipient female gender, higher number of HLA mismatch, lower baseline estimated glomerular filtration rate (eGFR), CMV seropositive donor, maintenance with cyclosporin (rather than tacrolimus) and higher number of maintenance immunosuppressive medications. The slope of eGFR decline was steeper in recipients with a history of DNA virus infection irrespective of the virus type. Further, GFR declined faster with an increasing number of different viral infections. Death-censored graft loss adjusted for age, gender, total HLA mismatch, baseline eGFR and acute rejection was significantly higher in recipients with a history of DNA virus infection than those without infection (adjusted hazard ratio (aHR, 1.74, 95% CI, 1.08–2.80)). In contrast, dialysis-free survival did not differ between the two groups of recipients (aHR, 1.13, 95% CI, 0.88–1.47). Conclusion: Post-transplant DNA viral infection is associated with a higher risk of allograft loss. Careful management of immunosuppression and close surveillance of at-risk recipients may improve graft outcomes.