Mendelian traits are considered as the lower end of the complexity spectrum of heritable phenotypes. However, more than a century after the rediscovery of Mendel's law, the global landscape of monogenic variants as well as their effects and inheritance patterns within natural populations is still not well understood. Using the yeast Saccharomyces cerevisiae, we performed a species-wide survey o...

Over the last 10 to 15 years, animal and human observational studies have identified elevated levels of both proinflammatory secretory phospholipase A2-IIA and lipoprotein-associated phospholipase A2 as potential risk factors for coronary heart disease. However, Mendelian randomization, a genetic tool to test causality of a biomarker, and phase III randomized controlled trials of inhibitors of ...

One promise of molecular genetics for many of us was that a detailed knowledge of mutant alleles would permit accurate prediction of prognosis and better selection of therapeutic strategies for Mendelian disorders (1). This presumed predictive promise was naı̈ve and was based on a reductionist view of genotype-phenotype correlations, i.e., that a refined and specific knowledge of a mutation’s im...

The epilepsies are a heterogeneous group of disorders with many causes. However, a genetic aetiology may be present in up to 40% of patients, and this proportion is even higher in epilepsy of childhood onset. The past decade has seen spectacular advances in our understanding of the genetics of epilepsy at a molecular level, and several comprehensive reviews are available. 3 It is apparent that ...

From the Telethon Institute of Genetics and Medicine (M.A.D.M., A.L.) and the Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche (A.L.) — both in Naples, Italy; and Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy (M.A.D.M.). Address reprint requests to Dr. De Matteis at the Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Naples, Italy, or at...

The identification of genotyping errors is an important issue in mapping complex disease genes. Although it is common practice to genotype multiple markers in a candidate region in genetic studies, the potential benefit of jointly analyzing multiple markers to detect genotyping errors has not been investigated. In this article, we discuss genotyping error detections for a set of tightly linked ...

OBJECTIVE The purpose of this study was to assess the mode of inheritance for obsessive-compulsive disorder (OCD) in families ascertained through pediatric probands. METHODS We ascertained 52 families (35 case and 17 control families) through probands between the ages of 10 and 17 years. Direct interviews were completed with 215 individuals. Family informant data were collected on another 450...

Many biomarkers are associated with type 2 diabetes (T2D) risk in epidemiological observations. The aim of this study was to identify and summarize current evidence for causal effects of biomarkers on T2D. A systematic literature search in PubMed and EMBASE (until April 2015) was done to identify Mendelian randomization studies that examined potential causal effects of biomarkers on T2D. To rep...

Recently, whole-genome sequencing, especially exome sequencing, has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. However, it is unclear whether this approach can be generalized and effectively applied to other Mendelian diseases with high locus heterogeneity. Moreover, the current exome sequencing approach has limitations such as false positi...

BACKGROUND There is considerable interest in the use of next-generation sequencing to help diagnose unidentified genetic conditions, but it is difficult to predict the success rate in a clinical setting that includes patients with a broad range of phenotypic presentations. METHODS The authors present a pilot programme of whole-exome sequencing on 12 patients with unexplained and apparent gene...