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Researchers have made dramatic inroads into the study of polygenic and other complex human diseases, due in large part to knowledge of the human genome sequence, the generation of widespread markers of genetic variation, and the development of new technologies that allow investigators to associate disease phenotypes with genetic loci. Although polygenic diseases are more common than single-gene disorders, studies of monogenic diseases provide an invaluable opportunity to learn about underlying molecular mechanisms, thereby contributing a great deal to our understanding of all forms of genetic disease.

The external environment's effects upon genes can influence disease, and some of these effects can be inherited in humans. Studies investigating how environmental factors impact the genetics of an individual's offspring are difficult to design. However, in certain parts of the world in which social systems are highly centralized, environmental information that might have influenced families can be obtained. For example, Swedish scientists recently conducted investigations examining whether nutrition affected the death rate associated with cardiovascular disease and diabetes and whether these effects were passed from parents to their children and grandchildren (Kaati et al., 2002). These researchers estimated how much access individuals had to food by examining records of annual harvests and food prices in Sweden across three generations of families, starting as far back as the 1890s. These researchers found that if a father did not have enough food available to him during a critical period in his development just before puberty, his sons were less likely to die from cardiovascular disease. Remarkably, death related to diabetes increased for children if food was plentiful during this critical period for the paternal grandfather, but it decreased when excess food was available to the father. These findings suggest that diet can cause changes to genes that are passed down though generations by the males in a family, and that these alterations can affect susceptibility to certain diseases. But what are these changes, and how are they remembered? The answers to questions such as these lie in the concept of epigenetics.

Genetic studies of human disease are more challenging to perform in sub-Saharan Africa because genetic diversity is greater than in other populations. This pilot will increase our understanding of African genome variation and enable the design of large-scale genetic association studies in the region. Studies into the genetic basis of disease in European populations have made major advances in the past few years, yet similar studies in sub-Saharan Africa have been slower to develop. The high level of genetic diversity that exists in populations from sub-Saharan Africa makes genetic associations with disease more difficult to identify. The African Genome Variation Project aims to collect essential information about the structure of African genomes to provide a basic framework for genetic disease studies in Africa.

Parkinson's is a result of the loss of cells in various parts of the brain, including one portion that produces the neurotransmitter dopamine. Dopamine is essential for being able to move in a coordinated way, so the loss of dopamine causes the tremors often associated with the condition. While the exact cause of Parkinson's is unknown, genetics and environment are contributing factors. Most cases occur in patients with no family history of Parkinson's disease, but there are 13 gene mutations that have been linked to either causing the disease or increasing one's risk of developing it. Certainly not everyone who carries these gene mutations develops Parkinson's, but identifying these genetic indicators is the beginning of developing more precise treatments.

A powerful tool called pVAAST that combines linkage analysis with case control association has been developed to help researchers and clinicians identify disease-causing mutations in families faster and more precisely than ever before. The researchers describe cases in which pVAAST (the pedigree Variant Annotation, Analysis and Search Tool) identified mutations in two families with separate diseases and a de novo or new variation in a 12-year-old who was the only one in his family to suffer from a mysterious and life threatening intestinal problem.

Scientists and healthcare professionals initially exhibited little concern over the Zika virus even after evidence of human infection was first identified in 1952; Zika appeared to be both rare and unassociated with morbidity or mortality. Around 2015 all of this changed as journalists, scientists, public health officials, and laypeople scrambled to learn about its varied modes of transmission and devastating consequences (e.g., birth defects and autoimmune disorders). Although research continues to rapidly evolve, this case study directs students to reliable scientific sources (e.g., Centers for Disease Control and World Health Organization) that will likely continue to provide the most current information in order to explore questions such as: Where did the virus come from? How does it spread? What can we do to prevent it? Students will also consider the public health challenges and possible solutions associated with emerging infectious diseases. The case was originally written for an upper-level biology or public health course in which students already have some basic background knowledge regarding viruses, vaccines, and infectious disease.

Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs) and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a "risk" allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders.

Women who are overweight while pregnant are more likely to have babies who are biologically older than those born to women of a healthy weight. This could put the babies at a higher risk of developing chronic diseases later in life, and may reduce their life expectancy. Our biological age is linked to the length of our telomeres - bits of DNA that cap the ends of our chromosomes. Our telomeres shrink every time our cells divide, and continue to shorten throughout life. "Short telomeres have been associated with cardiovascular disease, type 2 diabetes and atherosclerosis," says Tim Nawrot at Hasselt University in Belgium.

Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation, nor death from shock, thus restricting pathogenesis studies to non-human primates. Here we show that mice from the Collaborative Cross exhibit distinct disease phenotypes following mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, likely mediated by the susceptibility allele Tek. These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever.

Germ theory states that specific microscopic organisms are the cause of specific diseases. The theory was developed, proved, and popularized in Europe and North America between about 1850 and 1920. Because its implications were so different from the centuries-old humoral theory, germ theory revolutionized the theory and practice of medicine and the understanding of disease. It was, however, compatible with existing ideas about health, especially those associated with 19th-century hygiene and sanitation.

The researchers, Eicke Latz at the University of Bonn and colleagues, followed up on the parents' hypothesis and found that in mice, cyclodextrin indeed blocked plaque formation, melted away plaques that had already formed in arteries, reduced atherosclerosis-associated inflammation, and revved up cholesterol metabolism-even in rodents fed cholesterol-rich diets. In petri dish-based tests, the researchers found that the drug seemed to have the same effects on human cells and plaques.

This interrupted case study was inspired by and uses data from one of the largest commercial restaurant associated outbreaks of norovirus reported in the literature. It applies basic principles of epidemiology and outbreak investigation to a shellfish-linked norovirus outbreak at a Michelin star restaurant in the UK in 2009. The details of the case are taken directly from the report that was produced by the health protection agency and publications that followed. Students take on the role of an infection control team (ICT) that is responsible for identifying the extent and source of the outbreak. They are taken through different stages of the outbreak investigation and at each stage asked what their team would do in response to given pieces of information. Specifically, students uncover the scope and source of the outbreak using descriptive and basic analytical epidemiology methods. The case is suitable for first or second year introductory courses in microbiology, epidemiology, or other infectious disease related topics.

At about 3 billion letters long, reading and finding anything meaningful in the human genome is a daunting task. But that's just what genome researchers do. This interactive feature provides a microscopic view of some of what they've found on our 24 chromosomes, including the locations of about 200 different genes, especially those that have been associated with disease.

Calorie restriction has long been studied as a way to extend lifespan in animals. It has been associated with the ability to reduce the risks of cardiovascular and other diseases and to improve overall health. Now, researchers at Chang Gung University in Taiwan have found that calorie restriction can ...

A zebrafish model of a rare genetic disease has revealed an unexpected regulatory pathway for cholesterol absorption and processing. The findings, reported in the Journal of Molecular Medicine, were "quite surprising and have the potential to teach us about the basic physiology of cholesterol management," said Ela Knapik, M.D., associate professor of Medicine and Cell and Developmental Biology.

This integrative case study is based on real events that the author experienced with her ten-year-old daughter. Although the names have been changed, all of the events (symptoms, diagnoses and treatments, types of healthcare professionals) are recorded exactly as they occurred. Both asthma and pneumonia are common in the United States (and globally). Many of the drugs described in the case study are frequently prescribed for a wide variety of ailments. The four "episodes" that constitute the case cover 1) a study of asthma triggers, incidence and treatment; 2) side effects and possible medication errors associated with steroids; 3) causes, diagnosis, treatment and prevention of community-acquired bacterial pneumonia; and 4) the mechanism of action of two different antibiotics. The "epilogue" explores a few larger themes related to healthcare and public health (e.g., continuity of care, drug resistance, asthma prevention programs). The case study could be used in an undergraduate, upper-level, infectious disease, microbiology, public health or physiology course or in a graduate-level health professions program.

The largest genome-wide association study to date, involving more than 300 institutions and more than 250,000 subjects, roughly doubles the number of known gene regions influencing height to more than 400. The study provides a better glimpse at the biology of height and offers a model for investigating traits and diseases caused by many common gene changes acting together.

A worldwide study of the DNA of 100,000 women has discovered two new genetic variants associated with an increased risk of breast cancer. The genetic variants are specifically linked to the most common form of breast cancer, oestrogen receptor positive, and provide important insights into how the disease develops.

Life on Earth is intimately connected to the natural cycles of light and dark that make up a 24-hour day. For plants, animals, and even bacteria, these circadian rhythms control many biological functions. Humans can overrule their body clocks, but at a price: People whose circadian rhythms are regularly disrupted-by frequent jet lag or shift work, for example-are more vulnerable to diabetes, obesity, cardiovascular disease, and cancer. There are various theories to explain these associations, and researchers now have a new player to consider: the bacteria that live in the digestive tract. According to a study in mice and a small group of human volunteers, the internal clocks of these gut microbes sync up with the clocks of their hosts. When our circadian rhythms get out of whack, so do those of our bacteria.

This flipped case study tells the story of Joyce, a biology student who notices the development of some unusual symptoms (foot slapping and slurred speech) in her mother. In an effort to understand the cause, Joyce views a documentary-style trigger video (created by the case author) that suggests to Joyce that her mom may in fact have amyotrophic lateral sclerosis or ALS. The rest of the case walks Joyce through understanding how normal neurons compare to neurons in ALS patients and how that might affect muscle function. The case explores the link between genes, particularly SOD-1, to the formation of malformed proteins and its potential role in the development of ALS. The case concludes with a discussion of drug development and highlights the timeline and costs associated with drug discovery as Joyce becomes concerned about the lack of drugs in the pipeline for ALS, which her mother is ultimately diagnosed with. The case is appropriate for a number of classes including general biology, biotechnology, anatomy and physiology, upper level-cell biology, or any human health and disease-related course.