Legacy of Plant Virology in Croatia-From Virus Identification to Molecular Epidemiology, Evolution, Genomics and Beyond.

This paper showcases the development of plant virology in Croatia at the University of Zagreb, Faculty of Science, from its beginning in the 1950s until today, more than 70 years later. The main achievements of the previous and current group members are highlighted according to various research topics and fields. Expectedly, some of those accomplishments remained within the field of plant virology, but others make part of a much-extended research spectrum exploring subviral pathogens, prokaryotic plant pathogens, fungi and their viruses, as well as their interactions within ecosystems. Thus, the legacy of plant virology in Croatia continues to contribute to the state of the art of microbiology far beyond virology. Research problems pertinent for directing the future research endeavors are also proposed in this review.

Next-generation sequencing technologies and their application to the study and control of bacterial infections.

BACKGROUND: With the efficiency and the decreasing cost of next-generation sequencing, the technology is being rapidly introduced into clinical and public health laboratory practice. AIMS: The historical background and principles of first-, second- and third-generation sequencing are described, as are the characteristics of the most commonly used sequencing instruments. SOURCES: Peer-reviewed literature, white papers and meeting reports. CONTENT AND IMPLICATIONS: Next-generation sequencing is a technology that could potentially replace many traditional microbiological workflows, providing clinicians and public health specialists with more actionable information than hitherto achievable. Examples of the clinical and public health uses of the technology are provided. The challenge of comparability of different sequencing platforms is discussed. Finally, the future directions of the technology integrating it with laboratory management and public health surveillance systems, and moving it towards performing sequencing directly from the clinical specimen (metagenomics), could lead to yet another fundamental transformation of clinical diagnostics and public health surveillance.

Primer Part 1-The building blocks of epilepsy genetics.

This is the first of a two-part primer on the genetics of the epilepsies within the Genetic Literacy Series of the Genetics Commission of the International League Against Epilepsy. In Part 1, we cover the foundations of epilepsy genetics including genetic epidemiology and the range of genetic variants that can affect the risk for developing epilepsy. We discuss various epidemiologic study designs that have been applied to the genetics of the epilepsies including population studies, which provide compelling evidence for a strong genetic contribution in many epilepsies. We discuss genetic risk factors varying in size, frequency, inheritance pattern, effect size, and phenotypic specificity, and provide examples of how genetic risk factors within the various categories increase the risk for epilepsy. We end by highlighting trends in epilepsy genetics including the increasing use of massive parallel sequencing technologies.

Genetic Epidemiology and Public Health: The Evolution From Theory to Technology.

Genetic epidemiology represents a hybrid of epidemiologic designs and statistical models that explicitly consider both genetic and environmental risk factors for disease. It is a relatively new field in public health; the term was first coined only 35 years ago. In this short time, the field has been through a major evolution, changing from a field driven by theory, without the technology for genetic measurement or computational capacity to apply much of the designs and methods developed, to a field driven by rapidly expanding technology in genomic measurement and computational analyses while epidemiologic theory struggles to keep up. In this commentary, we describe 4 different eras of genetic epidemiology, spanning this evolution from theory to technology, what we have learned, what we have added to the broader field of public health, and what remains to be done.

Twenty years of bacterial genome sequencing.

Twenty years ago, the publication of the first bacterial genome sequence, from Haemophilus influenzae, shook the world of bacteriology. In this Timeline, we review the first two decades of bacterial genome sequencing, which have been marked by three revolutions: whole-genome shotgun sequencing, high-throughput sequencing and single-molecule long-read sequencing. We summarize the social history of sequencing and its impact on our understanding of the biology, diversity and evolution of bacteria, while also highlighting spin-offs and translational impact in the clinic. We look forward to a 'sequencing singularity', where sequencing becomes the method of choice for as-yet unthinkable applications in bacteriology and beyond.

Making blood 'Melanesian': fieldwork and isolating techniques in genetic epidemiology (1963-1976).

'Isolated' populations did not exist unproblematically for life scientists to study. This article examines the practical and conceptual labour, and the historical contingencies that rendered populations legible as 'isolates' for population geneticists. Though a standard historiographical narrative tells us that population geneticists were moving from typological understandings of biological variation to processual ones, cultural variation was understood as vulnerable to homogenisation. I chart the importance that D. Carleton Gajdusek placed on isolates from his promotion of genetic epidemiology in WHO technical reports and at a Cold Spring Harbour symposium to his fieldwork routines and collection practices in a group of South Pacific islands. His fieldwork techniques combined social, cultural and historical knowledge of the research subjects in order to isolate biological descent using genealogies. Having isolated a population, Gajdusek incorporated biological materials derived from that population into broad categories of 'Melanesian' and 'race' to generate statements about the genetics of abnormal haemoglobins and malaria. Alongside an analysis of Gajdusek's practices, I present different narratives of descent, kinship and identities learned during my ethnographic work in Vanuatu. These alternatives show tacit decisions made pertaining to scale in the production of 'isolates'.

Celebrating the 30th anniversary of genetic epidemiology: how to define our scope?

We review the scope of the scientific discipline genetic epidemiology by considering the steps of genetic epidemiologic research. Starting from the classical definition of genetic epidemiology as provided by Morton and Chung [1978, ISBN-13: 9780125080507], we propose a slightly modernized definition of the term genetic epidemiology.

Five classic articles in genetic epidemiology.

The relatively new field of genetic epidemiology has witnessed some exciting leaps forward in our quest to understand the population and familial nature of genetic inheritance. We have witnessed the mapping of thousands of genetic loci contributing to both mendelian and complex diseases, and new high-throughput, low-cost sequencing technologies promise to uncover even more. Here I highlight five publications that have shaped how we think about and conduct the task of unraveling the genetic causes of disease on a population scale.

Molecular epidemiology of tuberculosis in England, 1998.

SETTING: England. OBJECTIVE: To investigate the proportion of tuberculosis (TB) cases attributable to recent transmission and factors associated with clustering. DESIGN: Demographic, clinical and microbiological surveillance data were collated from all new culture-confirmed cases in 1998. Using insertion sequence (IS) 6110 restriction fragment length polymorphism (RFLP) typing, strains were classified as clustered (identical patterns) or unique and risk factors were determined using multivariable logistic regression. RESULTS: RFLP patterns were available for 2265 of 3713 (61%) cases: 1808 had >or=5 IS6110 copies, while 372 cases were in 152 clusters, giving an estimated proportion due to recent transmission of 12.2%.Pulmonary disease (aOR 1.6; 95%CI 1.1-2.2), previous treatment (aOR 3.7; 2.2-6.5) and homelessness (aOR 5.5; 1.2-24.1) were independent risk factors for clustering. Fourteen per cent of patients of Indian subcontinent origin were clustered compared with 27% of white patients. Many clusters spanned ethnic groups (45%) and geographical regions (47%). CONCLUSION: The calculated proportion of TB cases due to recent transmission is low.Adjusting for missed cases and study duration, it increases to 27.6%. Many cases may arise from reactivation or acquisition outside England. Transmission within England accounted for approximately one in four cases and occurred over wide geographic areas, between ethnic groups and among the homeless. Molecular epidemiology can inform local and national public health action.

The hepatitis C virus epidemic in Cameroon: genetic evidence for rapid transmission between 1920 and 1960.

Hepatitis C virus (HCV) infection in Cameroon is characterized by widespread seropositivity and great virus genetic diversity (3 genotypes and over 10 subtypes). A total of 244 HCV NS5B sequences of 382-405 bp long (95 type 1, 58 type 2, and 91 type 4) were phylogenetically analyzed to estimate the history of the HCV epidemic in Cameroon. The newly developed Bayesian coalescent approach was used to infer the history of each HCV type. The estimated dates of the most recent common ancestors (MRCA) for genotypes 1 (1500; 95% confidence interval (95% CI): 1300-1650) and 4 (1500; 95% CI: 1350-1700) were in the same range, while the date for genotype 2 MRCA (1600; 95% CI: 1400-1750) was slightly more recent. The mean genetic distance between HCV genotype 1 sequences was greater than that of HCV type 4 sequences, itself greater than that of HCV type 2 sequences. The initial infected populations of all three genotypes did not grow until recently, when they grew exponentially. The growth rate has now begun to slow, with a less steep exponential growth curve. The period of exponential growth of all the three genotypes was between 1920 and 1960. These results (i) confirm that HCV genotypes 1 and 4 have produced long-term endemics, (ii) suggest that genotype 2 was introduced into Cameroon more recently, and (iii) indicate that the exponential spread of the three genotypes between 1920 and 1960 coincided with the mass campaign against trypanosomiasis and mass vaccinations in Cameroon.