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• Genetics of Coronary Artery Disease in Alaskan Natives
• Genetics of Atherosclerosis in Mexican Americans: San Antonio Family Heart Study
• Mapping Drug Resistance Genes in the Malaria Parasite Plasmodium falciparum
• SOLAR: Sequential Oligogenic Linkage Analysis Routines
• Strong Heart Family Study

Summary

To what degree do we inherit qualities like life expectancy, predisposition to disease, and personal skills and behaviors? What are the specific genetic factors that are involved in shaping our characteristics? These are the key questions of my research group. While it has long been recognized that both environmental factors as well as genetic factors shape our existence, the identification of specific genetic factors involved in human disease etiology has only become possible fairly recently. Over the last decade, a technological revolution - not unlike that in computer technology - has taken place in molecular biology, allowing us to obtain detailed data on our individual genetic constitution on a scale unimaginable only a few years ago. Armed with such mounts of genomic data, scientists all over the world are now trying to identify the genetic origins underlying the common diseases of aging, such as cancer, heart disease or diabetes. There have been many successes and hopeful signs, but also many instances when the complexity of our organism is still proving a good guardian of its many secrets.

To overcome this hurdle, my research group works on two aspects of genetic epidemiology, namely the development of sophisticated statistical methods and their application to well-designed human datasets. This dichotomy of focus is important because it avoids the development of statistical methods that have no practical utility; because real data provides the impetus and ideas for the development of novel statistical and computational methods; and because deep understanding of statistical methodology is critical in avoiding pitfalls in designing applied studies and in interpreting the obtained results. Our applied research projects cover a wide variety of human conditions, ranging from rare diseases of early onset (such as many so-called Mendelian disorders), common diseases of late onset (such as many of the so-called complex disorders), quantitative biomarkers of disease or other conditions that are not directly related to a disease, including presently quantitative factors related to cardiovascular disease and diabetes, as well as risk of schizophrenia, lupus, and infectious diseases.

One current research focus is the genetic investigation of gene expression. Most human genes act by generating proteins that exert their functions in the human body. An intermediary between the information encoded in our DNA and the proteins is RNA, and it is now possible to simultaneously assess the activity of virtually all of our genes by measuring the abundance of RNA molecules being present in a particular tissue. We are interested in examining the genetic regulation of gene expression because it is thought that many of the genetic factors influencing the risk of common diseases are subtle changes to our DNA that result in alterations in the quantity, location and/or timing of gene expression. In addition, we are interested in statistical methodology for integrating gene expression data with other genomic data, to more fully utilize the information contained in different genomic data types in an attempt to unravel the genetic mysteries of human diseases.

Another focus is on the genetic factors influencing the risk of common infections. Hidden chronic infections are increasingly thought to play an important role in many aging-related diseases and may contribute to systemic or localized inflammation that is a hallmark of atherosclerosis and other disease conditions common in advanced age. We measured over 10 viral and bacterial pathogens in Mexican Americans from around San Antonio and recently succeeded in identifying a factors located in the HLA region of chromosome 6 that influences antibody titer levels to Epstein-Barr virus that can lead to mononucleosis and more serious diseases such as several cancers.

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