Dr. Brutsaert’s specialization is the adaptive response of populations native to high altitude, especially in the Andes. In general he is interested in the origins of complex-trait variability from a physiological, developmental, genetic, and evolutionary perspective. He has also branched out into other research areas, which include preliminary studies of obesity and diabetes in a Native-American population in Costa Rica; and he has planned research in the area of fetal programming as it affects human body composition, glucose tolerance, and human physical performance.
The basic goal of Brutsaert’s recent research conducted in Peru has been to apply a new molecular-based approach to the study of human altitude adaptation based on population admixture and migration status. His studies exploit several aspects of Andean history to unravel the origins and effects of gene, environment, and gene-environment interaction on traits related to life at high altitude. First, Native-American groups in the Andes have been exposed to hypobaric hypoxia for millennia, raising the possibility of genetic adaptation. Second, there has been a recent trend to urbanization in South America, with large-scale migrations of highlanders to lowland cities; and these migrations allow the evaluation of environmental effects that work through the growth and development process (i.e., developmental effects). Third, since the early 1500s, the Andes have been a region of genetic contact (admixture) between previously separated Spanish and Native-American populations. This allows assessment of the biogeographic ancestry proportion for each study subject using a panel of specially selected Ancestry Informative Markers (AIMS). The long term goal is to apply a gene-mapping strategy known as admixture mapping to identify loci underlying complex trait variability in the Andes.
A number of articles have been published from the Peruvian work in the last three years. Articles in the American Journal of Physical Anthropology and the American Journal of Applied Physiology describe the basic study design in Peru and show an association of Quechua ancestry with traits that reflect hypoxia sensitivity/tolerance. An article in Placenta describes a basic methodology to interrogate the genome for signatures of selection in response to hypobaric hypoxia and is based in part on the Peruvian DNA samples. An article in Human Genomics describes the library of useful ancestry informative markers and applies these to describe historical patterns of human genetic variation. Most recently, Brutsaert’s article in the American Journal of Physiology shows that ancestry explains much of the unique ventilatory pattern and respiratory control in Quechua. This latter paper has become the basis for a grant proposal submitted to NIH and described below.
Brutsaert has received internal support from CSDA to allow him and his team to conduct work preliminary to the submission of a proposal for external funding. In particular, he has received this support for a project, “Preliminary Studies of Metabolic Syndrome in Costa Rican Chibchan,” in order to conduct a communitywide household survey of population health in a Native-American community in Costa Rica. The work is interdisciplinary and involves 5 faculty members from the Albany Department of Anthropology and an additional 4-5 faculty from the Department of Anthropology at the Universidad de Costa Rica, San Jose.
Thanks in part to the support his work has received at CSDA, Brutsaert has two proposals under review. One, an R01 that has been revised after a previous submission (“Complex trait analysis using admixture in Quechua”), will allow him to continue his work in Peru and to develop his admixture-mapping approach. The other, an R03 (“Fetal Programming and Human Physical Performance”), represents the extension of his interest into fetal programming. Brutsaert will also continue his work with Tim Gage and others on diabetes and diabetes-related phenotypes in Costa Rican Native-American population.
Brutsaert’s altitude work makes use of admixture and migration (both fundamental demographic processes) and seeks to quantify ancestry proportion. The latter offers an alternative to the concept of race, which is frequently used (or abused) as a categorical independent variable in population-based research. Brutsaert’s work in Costa Rica has implications for understanding the obesity epidemic in the US. The anticipated work in fetal programming is important, not only for the basic science it represents, but also because it would serve as a validation for a number of potential biomarkers (related to human performance, like grip strength) that could be useful for population-based approaches seeking to understand population health, senescence, and so forth.
Use of infrastructure cores and activities
Brutsaert has made extensive use of center staff to help in the preparation and submission of grant proposals. Dr. Walter Ensel, the CSDA Proposal Specialist, has played an indispensable role in the submission of two R01 grants and one R03 grant. If any of these grants is funded, Brutsaert will make use of core facilities for grant administration and data analysis.