Research orientation
My research is focused primarily on the genetic
and
environmental risk
factors for type 2 diabetes in American Indians,
a population
disproportionately affected by this
disorder. I investigate these
factors using statistical genetics
methods. In my secondary
research, I use paleopathology and skeletal
biology to examine the use
and treatment of domesticated dogs in
prehistory. These disparate
research areas are connected by my interest in
the relationship between
biological variation, cultural practices, and
the
environment.
My anthropological genetics research is broadly
focused
on the factors
contributing to complex phenotypes (traits) in
living humans.
Variation in complex phenotypes is influenced by
the combined effects
of multiple genetic and environmental factors
and their
interactions. "Environment" includes age,
sex, and lifestyle
variables such as diet or smoking. Most
phenotypes are complex,
for example, stature, handedness, or
susceptibility to diabetes and
many other diseases of public health
importance. The
identification of genetic and other complex
disease risk factors is
essential to understanding biologic pathways and
for developing disease
treatments and interventions.
The specialized statistical methods that I use
to
identify and
characterize the genetic and environmental
components of complex
phenotypes include linkage analyses, which are
used to map variation in
phenotypes to chromosomal regions represented by
genetic markers, and
tests for association between phenotype
variation and single nucleotide
polymorphisms (SNPs) within genes.
Ongoing genetics research
In collaboration with several Native American
communities in Oklahoma
and with the OU Molecular Anthropology
Laboratory, I am using
statistical genetics methods and information
from Native American
families to investigate type 2 diabetes risk
factors in American
Indians. Type 2 diabetes is an endocrine
disorder characterized by
insulin resistance, impaired insulin secretion,
and hyperglycemia.
American Indians and Alaska Natives have an
age-adjusted diabetes
prevalence more than twice that of non-Hispanic
whites. A combination
of genetic, epigenetic and environmental factors
may underlie this
disparity. The specific aim of the study I am
currently involved with
is to use candidate gene sequencing to identify
novel and common
variants that contribute to type 2 diabetes risk
in American Indians.
My long-term goal is to identify genetic and
environmental risk factors
for type 2 diabetes that are of use in the
development of culturally
appropriate intervention and treatment
strategies.
Previous genetics research
My postdoctoral research focused on the genetic
and
environmental
components of quantitative variation in
hemostasis (blood clotting)
phenotypes. Data were from families
participating in the San Antonio
Family Heart Study (SAFHS), an investigation of
cardiovascular disease
in low-income Hispanic families. Cardiovascular
disease is the leading
cause of death in this population. The
hemostasis phenotypes are risk
factors for cardiovascular diseases. Using a
variance components-based
approach and after accounting for measured
covariates including age,
sex, medications, and lifestyle factors, I found
that genetic factors
contributed significantly to variation in each
of the hemostasis
phenotypes, with additive genetic effects
explaining between 20 and 60
percent phenotypic variation. Significant
genetic correlations occurred
between type 2 diabetes and several hemostasis
phenotypes, suggesting
that the same genes that influence
cardiovascular disease risk
pleiotropically contribute to type 2 diabetes
risk. In a related
project, I used genome-wide linkage scans to
identify a significant
quantitative trait locus (QTL) for
thrombin-activatable fibrinolysis
inhibitor (TAFI) on chromosome 13q.
In addition to my research on complex disease
risk, I investigated the
genetic components of normal variation in hand,
foot and eye
preference, using data from the San Antonio
Family Diabetes/Gallbladder
Study. There has been considerable interest
among anthropologists and
others in the evolution of human handedness
because of its proposed
link to the evolution of lateralized language
centers in the brain.
However, the factors contributing to side
preference are poorly
understood. I found a weak but significant
heritability for
self-reported handedness and other side
preferences, indicating that
genes are an important component of laterality.
Genome-wide linkage
scans revealed QTLs for hand preference and eye
preference on
chromosomes 12q and 22pter, respectively.
Skeletal biology research
I use skeletal biology and paleopathology to
investigate
the use and
treatment of dogs by Native Americans in
prehistory. Deliberate dog
burial, both within and outside of human graves,
was common in the
Midwest, Midsouth and Southeast during the
Archaic period (8000-3000
BP). Typically, Archaic peoples in these regions
were highly mobile
hunter-gatherers. A post-Archaic decline in the
number of dog burials
may reflect changes in the functional and/or
cultural roles of dogs in
Native American societies as sedentism increased
and food production
intensified. Although there has been
considerable speculation about dog
use in prehistory, much of our current
understanding is based on
ethnographic analogy rather than on direct
evidence. I used data from
455 dogs from Archaic through early historic
period archaeological
sites in Alabama, Kentucky, Tennessee, and
Illinois to investigate
geographic, temporal, and other variation in dog
health, size, and
demography. I found that during the Archaic
period, dogs that were
buried in human graves were significantly older
than dogs buried
elsewhere. In contrast, a dog's sex, size, and
life experience as
indicated by skeletal and dental pathologies did
not play a role in its
co-burial with humans.
Male dogs outnumbered females in all time
periods and in
all geographic
regions, potentially due to differential burial
by sex or to an
overrepresentation of males in the living dog
population. More males
would occur where females were culled for food
and/or to control the
population size, or where male dogs were more
highly valued and given
better care. Dog size was similar between
geographic regions, and in
contrast to earlier studies, I found no
significant size increase over
time. Patterns of variation in dental pathology
supported regional and
temporal differences in dog diet and activity.
For example, the
relatively greater number of carnassial and
molar tooth abscesses in
Archaic dogs from Kentucky and Tennessee versus
Alabama suggested that
the Alabama dogs had less access to
plaque-promoting foods including
carbohydrates. High frequencies of vertebral,
rib, and skull fractures
in all time periods and across geographic
regions was consistent with
abuse by humans, dog fights, and/or hunting
injuries. The frequency of
skull and rib fractures increased over time.
Dogs in all geographic
regions and time periods exhibited multiple
pathologies consistent with
use as beasts of burden.
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