The sperm factor: paternal impact beyond genes

The fact that sperm carry more than the paternal DNA has only been discovered just over a decade ago. With this discovery, the idea that the paternal condition may have direct implications for the fitness of the offspring had to be revisited. While this idea is still highly debated, empirical evidence for paternal effects is accumulating. Male condition not only affects male fertility but also offspring early development and performance later in life. Several factors have been identified as possible carriers of non-genetic information, but we still know little about their origin and function and even less about their causation. I consider four possible non-mutually exclusive adaptive and non-adaptive explanations for the existence of paternal effects in an evolutionary context. In addition, I provide a brief overview of the main non-genetic components found in sperm including DNA methylation, chromatin modifications, RNAs and proteins. I discuss their putative functions and present currently available examples for their role in transferring non-genetic information from the father to the offspring. Finally, I identify some of the most important open questions and present possible future research avenues

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Response to vaccination against hepatitis B in patients with Behcet's disease

ERKEK, BULENT/0000-0002-9041-341XWOS: 000231611700006PubMed: 16174066Background and Aims: Hepatitis B virus infection is an important public health problem in Turkey. Although hepatitis B vaccination is regarded as safe and effective for the general population, recommendations for hepatitis B immunization in patients with Behcet's disease are not clear. The aim of the present study was to elucidate the response of patients with Behcet's disease to hepatitis B vaccination and to determine whether hepatitis B vaccination has any adverse effects on the course of the disease. Methods: Thirteen patients with Behcet's disease and 15 healthy individuals were enrolled into a prospective study. All subjects received the 3-dose series of routine hepatitis B vaccine. Anti-hepatitis B surface response was evaluated 1-3 months after the third dose of vaccine. Results: The responder rates for patient and control groups were 12/13 (92.8%) and 14/15 (93.8%), respectively. Statistical analysis showed no significant difference between the two groups in terms of both the responder rates and mean antibody titers. Conclusions: These preliminary findings might suggest that the majority of patients with Behcet's disease develop protective antibody response after hepatitis B vaccination and that the immune response against hepatitis B surface antigen is adequate, efficient and intact. (C) 2005 Blackwell Publishing Asia Pty Ltd

Pruritus and intermittent jaundice as clinical clues for Fasciola hepatica infestation

ERKEK, BULENT/0000-0002-9041-341XWOS: 000238621100018PubMed: 16842334

Clinical and histopathological findings in Bannayan-Riley-Ruvalcaba syndrome

ERKEK, BULENT/0000-0002-9041-341X; ULKATAN, SEDAT/0000-0002-9288-7635WOS: 000232067800012PubMed: 16198785Bannayan-Riley-Ruvalcaba syndrome is a rare autosomal dominant genodermatosis with the classical triad of macrocephaly, genital lentiginosis, and intestinal polyposis. Characteristic mucocutaneous manifestations include vascular malformations, lipomatosis, speckled lentiginosis of the penis or vulva, facial verrucae-like or acanthosis nigricans-like lesions, and multiple acrochordons of the neck, axilla, and groin. We present a case of Bannayan-Riley-Ruvalcaba syndrome with macrocephaly, abnormal facies, lipoma, tender and painful arteriovenous hemangiomas, lymphangiokeratomas, musculoskeletal abnormalities, and localized myopathy. We also describe previously unreported findings, including peripheral neuropathy, punctate cystic changes in acral tubular bones, and enostosis of talus. Bannayan-Riley-Ruvalcaba syndrome needs recognition by dermatologists because affected patients may present with mucocutaneous and subcutaneous lesions that may simulate other dermatological disorders

Introduction to epigenetic inheritance: Definition, mechanisms, implications and relevance.

Complex phenotypes result from the interaction between genetic and environmental informations. Almost a decade ago, the discovery of acquired epigenetic inheritance has shown that individual’s environmental experiences can influence developmental and phenotypic trajectories across several generations. The field is now starting to unveil the molecular mechanisms, while its relevance for complex disease risk and adaptive evolution is still unclear and strongly debated. The aim of this chapter is to introduce the reader to the concept of epigenetic inheritance, provide an overview on the underlying molecular determinants and highlight its potential relevance for individual’s susceptibility to complex, non-mendelian, diseases