Phenotypic outcomes of PKD1 compared with non-PKD1 genetically confirmed autosomal dominant polycystic kidney disease.

Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the most common monogenic cause of kidney failure. While identifying genetic variants predicts disease progression, characterization of recently described ADPKD-like variants is limited. We explored disease progression and genetic spectrum of genetically-confirmed ADPKD families with PKD1 and non-PKD1 variants.

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.

Survival in acute myeloid leukemia is associated with NKp44 splice variants.

NKp44 is a receptor encoded by the NCR2 gene, which is expressed by cytokine-activated natural killer (NK) cells that are involved in anti-AML immunity. NKp44 has three splice variants corresponding to NKp44ITIM+ (NKp44-1) and NKp44ITIM- (NKp44-2, and NKp44-3) isoforms. RNAseq data of AML patients revealed similar survival of NKp46+NKp44+ and NKp46+NKp44- patients.

Extracting tumor tissue immune status from expression profiles: correlating renal cancer prognosis with tumor-associated immunome.

Investigating the expression of genes in cancer-associated immune cells (immunome) is imperative for prognosis prediction. However, evaluating the expression of immune-associated genes within cancer biopsy is subject to significant inconsistencies related to the sampling methodology. Here, we present immFocus, a method for extracting immune signals from total RNA sequencing of tumor biopsies, intended for immunity depiction and prognosis evaluation.

Severe methylenetetrahydrofolate reductase deficiency: clinical clues to a potentially treatable cause of adult-onset hereditary spastic paraplegia.

Importance: Hereditary spastic paraplegia is a highly heterogeneous group of neurogenetic disorders with pure and complicated clinical phenotypes. No treatment is available for these disorders. We identified 2 unrelated families, each with 2 siblings with severe methylenetetrahydrofolate reductase (MTHFR) deficiency manifesting a complicated form of adult-onset hereditary spastic paraparesis partially responsive to betaine therapy.

Involvement of PTPN5, the gene encoding the striatal-enriched protein tyrosine phosphatase, in schizophrenia and cognition.

Objective: Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific member of the protein tyrosine phosphatase (PTP) family that has been implicated in learning and memory. In this study, we examined the association of the protein tyrosine phosphatase non-receptor 5 (PTPN5) gene, which encodes for STEP, with both schizophrenia and cognitive functioning in the Israeli Jewish population.

Methods: A schizophrenia (SZ) case-control study of 868 participants was carried out (286 patients and 582 controls).

Oxytocin and vasopressin genes are significantly associated with schizophrenia in a large Arab-Israeli pedigree.

We have previously studied the genetics of schizophrenia in a large inbred Arab-Israeli pedigree and found evidence for linkage on chromosome 20p13. This locus harbours four strong candidate genes for schizophrenia: atractin (ATRN), pantonate-kinase2 (PANK2), oxytocin (OXT) and arginine-vasopressin (AVP). In this study we further explored the association of these genes with schizophrenia in the pedigree and searched for the disease-causing variants.

Selected summaries from the XVII World Congress of Psychiatric Genetics, San Diego, California, USA, 4-8 November 2009.

The XVII World Congress of Psychiatric Genetics, sponsored by The International Society of Psychiatric Genetics (ISPG) took place in San Diego, California from 4 to 8 November 2009. Approximately 550 participants gathered to discuss the latest molecular genetic findings relevant to serious mental illness, including schizophrenia, mood disorders, substance abuse, autism, and attention deficit disorder. Recent advances in the field were discussed, including the genome-wide association studies results, copy number variation (CNV) in the genome, genomic imaging, and large multicenter collaborations.

Further evidence for association of the RGS2 gene with antipsychotic-induced parkinsonism: protective role of a functional polymorphism in the 3'-untranslated region.

RGS2 (regulator of G-protein signaling 2) modulates dopamine receptor signal transduction. Functional variants in the gene may influence susceptibility to extrapyramidal symptoms (EPS) induced by antipsychotic drugs. To further investigate our previous report of association of the RGS2 gene with susceptibility to antipsychotic-induced EPS, we performed a replication study.

Genome-wide linkage scan, fine mapping, and haplotype analysis in a large, inbred, Arab Israeli pedigree suggest a schizophrenia susceptibility locus on chromosome 20p13.

Linkage and association studies in schizophrenia have repeatedly drawn attention to several chromosomal regions and to genes within them. Conflicting patterns of association and the lack of a clear functional significance of the associated variants limit the interpretation of these results. The use of rare pedigrees, where genes with a major effect cause the disorder, has been proven beneficial in studies of other complex disorders.