Familial Variability of Disease Severity in Adult Patients With ADPKD.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic nephropathy and has striking familial variability of disease severity.

Methods: To better comprehend familial phenotypic variability, we analyzed clinical and pedigree data on 92 unrelated ADPKD kindreds with ≥2 affected individuals ( = 292) from an Irish population. All probands underwent genetic sequencing.

Rare disease gene association discovery from burden analysis of the 100,000 Genomes Project data.

To discover rare disease-gene associations, we developed a gene burden analytical framework and applied it to rare, protein-coding variants from whole genome sequencing of 35,008 cases with rare diseases and their family members recruited to the 100,000 Genomes Project (100KGP). Following triaging of the results, 88 novel associations were identified including 38 with existing experimental evidence. We have published the confirmation of one of these associations, hereditary ataxia with , and independent confirmatory evidence has recently been published for four more.

Optimizing prediction of response to antidepressant medications using machine learning and integrated genetic, clinical, and demographic data.

Major depressive disorder (MDD) is complex and multifactorial, posing a major challenge of tailoring the optimal medication for each patient. Current practice for MDD treatment mainly relies on trial and error, with an estimated 42-53% response rates for antidepressant use. Here, we sought to generate an accurate predictor of response to a panel of antidepressants and optimize treatment selection using a data-driven approach analyzing combinations of genetic, clinical, and demographic factors.

The transcription factor CUX1 negatively regulates invasion in castrate resistant prostate cancer.

Metastatic prostate cancer is treated with androgen ablation therapy but progress to castrate resistant prostate cancer (CRPC). This study aimed to investigate the role of CUX1 in CRPC using clinical samples and models. CUX1 expression was increased in androgen-independent cells compared to androgen-sensitive cells.

NKp44 and NKp30 splice variant profiles in decidua and tumor tissues: a comparative viewpoint.

NKp44 and NKp30 splice variant profiles have been shown to promote diverse cellular functions. Moreover, microenvironment factors such as TGF-β, IL-15 and IL-18 are able to influence both NKp44 and NKp30 splice variant profiles, leading to cytokine-associated profiles. Placenta and cancerous tissues have many similarities; both are immunologically privileged sites and both share immune tolerance mechanisms to support tissue development.