Picornavirus May Be Linked to Parkinson's Disease through Viral Antigen in Dopamine-Containing Neurons of Substantia Nigra.

Parkinson's disease (PD) is a neurodegenerative disease linked with the loss of dopaminergic neurons in the brain region called substantia nigra and caused by unknown pathogenic mechanisms. Two currently recognized prominent features of PD are an inflammatory response manifested by glial reaction and T-cell infiltration, as well as the presence of various toxic mediators derived from activated glial cells. PD or parkinsonism has been described after infection with several different viruses and it has therefore been hypothesized that a viral infection might play a role in the pathogenesis of the disease.

Demographic history and selection at HLA loci in Native Americans.

The American continent was the last to be occupied by modern humans, and native populations bear the marks of recent expansions, bottlenecks, natural selection, and population substructure. Here we investigate how this demographic history has shaped genetic variation at the strongly selected HLA loci. In order to disentangle the relative contributions of selection and demography process, we assembled a dataset with genome-wide microsatellites and HLA-A, -B, -C, and -DRB1 typing data for a set of 424 Native American individuals.

Extending the Enterovirus Lead: Could a Related Picornavirus be Responsible for Diabetes in Humans?

We found an association between the abundance of rodents in the wild and onset of type 1 diabetes (T1D) in humans. A picornavirus named Ljungan virus (LV) was subsequently isolated from wild bank voles. Both picornavirus-like particles detected by electron microscopy and LV antigen visualized by immunohistochemistry was seen in islets of Langerhans in diabetic wild bank voles.

Effectiveness of Antivirals in a Type 1 Diabetes Model and the Move Toward Human Trials.

A Picornavirus (Ljungan virus [LV]) originally found in bank voles has been associated with type 1 diabetes (T1D) in its wild rodent reservoir, but also associated with T1D in a laboratory rat model for the disease, the diabetes prone (DP) Bio Breeding (BB) rat. Successful treatment of diabetes in this rat model, using experimental antiviral compounds directed against picornavirus, has been reported. In the present study we show significant clinical response in DP-BB rats using antiviral compounds available for human use (Pleconaril, Efavirenz, and Ribavirin).

Picornavirus Identified in Alzheimer's Disease Brains: A Pathogenic Path?

We investigated formalin-fixed postmortem brain tissue from the hippocampus region of 18 AD cases and 11 age-matched controls using a polyclonal antibody against Ljungan virus (LV) capsid protein 1. Evidence of a LV antigen was found in all AD cases but in none of the control specimens ( < 0.0001).

Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance.

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows.

The Simons Genome Diversity Project: 300 genomes from 142 diverse populations.

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome.

Diabetes Prevention Through Antiviral Treatment in Biobreeding Rats.

A picornavirus (Ljungan virus) has been associated with diabetes in its wild rodent reservoir and in diabetes-prone biobreeding (DP-BB) rats. We attempted to alter the development of diabetes in DP-BB rats using two anti-picornavirus compounds (pleconaril and APO-N039), singly or in combination. Antiviral therapy was initiated 2 weeks before expected onset of diabetes.

Global diversity, population stratification, and selection of human copy-number variation.

In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations.

Whitey crumbles.

Despite scientific evidence to the contrary, cultural notions that incorrectly aggrandize genetic differences between ethnicities persist. New work on the genetic makeup of Europeans now shows even more definitively how false those notions are.

Ancient human genomes suggest three ancestral populations for present-day Europeans.

We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.

Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: the Genes-environments & Admixture in Latino Americans study.

Background: Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent.

Objective: We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping.

New reservoirs of HLA alleles: pools of rare variants enhance immune defense.

Highly polymorphic exons of the major histocompatibility complex (MHC, or HLA in humans) encode critical amino acids that bind foreign peptides. Recognition of the peptide-MHC complexes by T cells initiates the adaptive immune response. The particular structure of these exons facilitates gene conversion(GC) events, leading to the generation of new alleles.

Reconstructing Native American population history.

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood.

Spectrum of HLA associations: the case of medically refractory pediatric acute lymphoblastic leukemia.

Although studies of HLA and disease now date back some 50 years, a principled understanding of that relationship has been slow to emerge. Here, we examine the associations of three HLA loci with medically refractory pediatric acute lymphoblastic leukemia (pALL) patients in a case-control study involving 2,438 cases and 41,750 controls. An analysis of alleles from the class I loci, HLA-A and HLA-B, and the class II locus DRB1 illuminates a spectrum of extremely significant allelic associations conferring both predisposition and protection.

Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations.

The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products.

Contrasting patterns of nuclear and mtDNA diversity in Native American populations.

We report an integrated analysis of nuclear (autosomal, X- and Y-chromosome) short tandem repeat (STR) data and mtDNA D-loop sequences obtained in the same set of 22 Native populations from across the Americas. A north to south gradient of decreasing population diversity was observed, in agreement with a settlement of the Americas from the extreme northwest of the continent. This correlation is stronger with "least cost distances," which consider the coasts as facilitators of migration.

Ljungan virus detected in bank voles (Myodes glareolus) and yellow-necked mice (Apodemus flavicollis) from Northern Italy.

Identified in 1998, Ljungan virus (LV; Picornaviridae) causes type 1 diabetes-like symptoms and myocarditis in bank voles (Myodes glareolus) from Sweden and Denmark, and may be a zoonotic agent of several important diseases (e.g., intrauterine fetal death, type 1 diabetes, Guillain-Barré syndrome, and myocarditis).

Antiviral treatments reduce severity of diabetes in Ljungan virus-infected CD-1 mice and delay onset in diabetes-prone BB rats.

The effects of LV in two different species, CD-1 mice, without a genetic disposition for diabetes, and BB rats prone to T1D were examined. Male CD-1 mice that had been exposed to LV in utero developed a type 2-like diabetes with increased blood glucose, insulin levels and epididymal fat at the age of 10-15 weeks. Combination therapy including LV-antiserum and an antiviral drug, Pleconaril, significantly reduced the levels of blood glucose and insulin and the amount of abdominal fat.

Sudden infant death syndrome and Ljungan virus.

Ljungan virus (LV) has recently been associated with perinatal death in its natural rodent reservoir and also with developmental disorders of reproduction in laboratory mice. A strong epidemiological association has been found between small rodent abundance in Sweden and the incidence of intrauterine fetal death (IUFD) in humans. LV antigen has been detected in half of the IUFD cases tested.

Zoonotic Ljungan virus associated with central nervous system malformations in terminated pregnancy.

Background: The Ljungan virus (LV) has been shown to cause central nervous system malformations in laboratory mouse models. The LV has also been associated with intrauterine fetal death in humans. We investigated the presence of LV in a series of human hydrocephaly and anencephaly cases from elective abortions.