| CEEH Investigators published over 80 papers that directly benefited
from the CEEH resources and/or CEEH-fostered collaborations,
and cited the center grant number.
Gastrointestinal and Renal Toxicology Research Core
(RC1)
CEEH
investigators
in the Gastrointestinal and Renal
Toxicology Research Core (RC1) are interested in gene-environment
interactions in drug metabolism and disposition, particularly
as they affect liver and kidney function.
For
example, CEEH Investigators Kenneth Thummel (RC1
Director),
David Veenstra, Allan Rettie, and Debbie Nickerson (Carcinogenesis
Research Core) evaluated haplotypes in the vitamin K epoxide
reductase complex 1 (VKORC1) gene that plays an important role
in blood clotting, and in response to anticoagulant treatment
with the widely prescribed drug, warfarin. Warfarin is also
one of the most widely used rodenticides in the world. The
management of warfarin therapy is complicated by a wide variation
among patients in drug response. They conducted a retrospective
study of European-American patients receiving long-term warfarin
maintenance therapy, and identified 10 common non-coding VKORC1
single-nucleotide polymorphisms and inferred five major haplotypes.
They identified a low-dose haplotype group (A) and a high-dose
haplotype group (B). The two VKORC1 haplotype (groups A and
B) explained approximately 25 percent of the variance in dose.
Asian Americans had a higher proportion of group A haplotypes
and African Americans a higher proportion of group B haplotypes.
VKORC1 mRNA levels varied according to the haplotype combination.
Thus, they suggest that VKORC1 haplotypes can be used to stratify
patients into low-, intermediate-, and high-dose warfarin groups
and may explain differences in dose requirements among patients
of different ancestries. The data demonstrated that the molecular
mechanism of this warfarin dose response appears to be regulated
at the transcriptional level. (New England Journal of Medicine
2005; 352:2285-93). They followed this important work with
a study of warfarin effects in an Asian population. They found
that VKORC1 genotype is the dominant genetic influence on inter-individual
variability in warfarin dose in Hong Kong Chinese. The lower
mean dose of warfarin prescribed for Chinese, relative to Europeans,
appears to be a reflection of their preponderance of the warfarin-susceptibility
VKORC1 H1/H1 (homozygous group A) genotype. The Functional
Genomics Facility Core assisted in the genotyping in
these studies. (Pharmacogenet Genomics 2005, 15:687-91).
CEEH
investigator James Woods and affiliate
member Diana Echeverria used the services of the Functional
Genomics Facility Core to further explore the significance
of genetic polymorphisms in coproporphyringen oxidase, a key
enzyme in the breakdown of hemoglobin waste products. Previous
studies have demonstrated highly specific urinary porphyrin profile
(UPP) changes in response to mercury (Hg) exposure in animals
and human subjects and have defined the biochemical etiology
of this effect as selective alteration of the heme pathway enzymes,
uroporphyrinogen decarboxylase (UROD), and coproporphyrinogen
oxidase (CPOX) by Hg in the kidney. Ongoing validation studies
in a population of dental practitioners with low-level occupational
Hg exposure have demonstrated the predicted UPP change among
approximately 85% of subjects. This study focused on the genetic
etiology of an atypical porphyrinogenic response (APR) seen among
the remaining 15% of Hg-exposed subjects, characterized by excess
excretion of 4- and 5-carboxyl porphyrins and also of the atypical
ketoisocoproporphyrin (KICP). Automated DNA-sequencing-based
assays were developed to examine the 7 exons and flanking intron-exon
boundaries of the CPOX gene. Among several polymorphisms identified,
an A814C variant in exon 4 encoding a N272H substitution was
found to be predominant among subjects with the APR. Studies
suggest that this variant CPOX preferentially converts the upstream
5-carboxylporphyrin (5-CP) to KICP. By partially inhibiting the
5- to 4-decarboxylation step of UROD, Hg promotes 5-CP accumulation,
accounting for excess KICP excretion and the APR in Hg-exposed
subjects carrying the variant CPOX gene. This finding represents
the first report of a polymorphism in a human gene that modifies
the effect of Hg on a biological process. The APR might serve
as a biomarker of both Hg exposure and susceptibility to Hg toxicity.
(Toxicol Appl Pharmacol. 2005;206:113-20).
The
molecular modeling component of the Functional Proteomics
Facility Core and the genotyping services of the Functional
Genomics Facility Core were a key asset to studies
of the effects of polymorphisms in the CYP2C9 gene on warfarin
metabolism. CEEH Investigators Rettie, David
Veenstra,
and Christophe Verlinde collaborated to determine
the in-vitro and in-vivo effects of the CYP2C9*11 polymorphism
on (S)-warfarin metabolism. The *11 allele that results in mutation
of Arg335-->Trp occurred with a frequency of approximately
1% in Caucasian and African-American populations. Four subjects
carrying the *1/*11 genotype were identified in a clinical cohort
of 192 warfarin patients. Compared to control subjects with the
*1/*11 genotype (n=127), the *1/*11 group exhibited a 33% reduction
in warfarin maintenance dose, that was independent of study population
age or INR. In-vitro studies directed towards understanding the
mechanism of reduced in-vivo activity revealed very low levels
of holo-CYP2C9.11 expression in insect cells and decreased solubility
in the presence of detergent. Membrane preparations of CYP2C9.11
contained inactive P420 and exhibited a shorter half-life for
thermally induced conversion of P450 to P420 than CYP2C9.1. Metabolic
studies demonstrated that functional CYP2C9.11 possessed similar
(S)-warfarin hydroxylation regioselectivity and modestly reduced
catalytic efficiency relative to the wild-type enzyme. From these
results they concluded that in-vivo reduction in CYP2C9 (S)-warfarin
activity due to the CYP2C9*11 polymorphism may largely be a consequence
of decreased enzyme stability resulting in compromised expression
of holo-enzyme. Increased enzyme lability of CYP2C9.11 may be
related to improper folding due to the disruption of conserved
salt-bridge and hydrogen bonding contacts in the loop region
between the J and J' helices of the protein. (Pharmacogenet Genomics.
2005;15: 475-81).
Environmental Carcinogenesis Research Core (RC2)
CEEH
investigators in the Environmental Carcinogenesis
Research Core (RC2) are interested in gene-environment
interactions in cancer, ranging from basic laboratory studies
to population-based molecular epidemiology studies.
For
example, CEEH investigators David Eaton (CEEH
Director), Helmut
Zarbl, and Bradley Preston collaborated
on a project to examine which specific DNA repair pathways
are involved in the repair of DNA adducts formed by the potent
liver carcinogen, aflatoxin B1. To do this, they genetically
engineered a series of yeast haploid mutants defective in DNA
repair and cell cycle checkpoints to express human CYP1A2 that
activates AFB to its genotoxic metabolite. These yeast strains
were then used to investigate how these DNA adducts are repaired.
Cell survival and mutagenesis following aflatoxin B1 treatment
was assayed in strains defective in nucleotide excision repair
(NER) (rad14), postreplication repair (PRR) (rad6, rad18, mms2,
and rad5), homologous recombinational repair (HRR) (rad51 and
rad54), base excision repair (BER) (apn1 apn2), nonhomologous
end-joining (NHEJ) (yku70), mismatch repair (MMR) (pms1), translesion
synthesis (TLS) (rev3), and checkpoints (mec1-1, mec1-1 rad53,
rad9, and rad17). The results from the study suggest the involvement
of homologous recombination and nucleotide excision repair,
postreplication repair, and checkpoints in the repair and/or
tolerance of AFB1-induced DNA damage in the yeast model. Rev3
appears to mediate AFB1-induced mutagenesis when error-free
pathways are compromised. The results further suggest unique
roles for Rad5 and abasic endonuclease-dependent DNA intermediates
in regulating AFB1-induced mutagenicity. (Mol Cell Biol. 2005
Jul;25(14):5823-33). Using the cDNA microarrays, they also
examined the effects of AFB-DNA adduct formation on global
gene expression in yeast engineered to express human CYP1A2.
The genes activated by AFB(1)-treatment included RAD51, DUN1
and other members of the DNA damage response signature reported
in a previous study with methylmethane sulfonate and ionizing
radiation. However, unlike previous studies using highly cytotoxic
doses, environmental stress response genes were largely unaffected
by our dosing regimen. About half of the transcripts affected
are also known to be cell cycle regulated. The most strongly
repressed transcripts were those encoding the histone genes
and a group of genes that are cell cycle regulated and peak
in M phase and early G1. (Mut Res 593:121-42. Epub Aug 2005).
Using
a molecular epidemiology approach, CEEH investigators John
Potter and Joanna Lampe examined the
effects of a polymorphism in the biotransformation enzyme, UGT1A1,
to see whether the genetic variant altered how people respond
to dietary chemicals that influence the expression of the gene.
UGT1A1 is a conjugating biotransformation enzyme that plays a
role in maintaining levels of endogenous compounds (e.g., bilirubin)
and handling exogenous compounds, including carcinogens. The
UGT1A1*28 polymorphism results in decreased UGT1A1 promoter activity
due to 7 thymine-adenine (TA) repeats instead of the commonly
found 6 repeats. They investigated, in an observational study,
whether foods from the botanical families Cruciferae (e.g., broccoli),
Rutaceae (citrus), Liliaceae (e.g., onions), and Leguminosae
(legumes) were associated with increased UGT1A1 activity as indicated
by serum bilirubin concentrations and whether the effect varied
by UGT1A1*28 genotype, comparing those homozygous for the [TA](7)-repeat
allele (7/7) to homozygous wild-types (6/6) and heterozygotes
(6/7) combined. They found a significant inverse association
between all 3 bilirubin measures and interaction of UGT1A1*28
genotype with Cruciferae intake; individuals with the 7/7 genotype
had reduced bilirubin concentrations with increased intake of
cruciferous vegetables, whereas individuals with the 6/6 or 6/7
genotype did not. From these results they suggest that individuals
with decreased UGT1A1 activity due to the 7/7 genotype may be
at greater risk for carcinogenesis from dietary carcinogens (e.g.,
heterocyclic amines, polycyclic aromatic hydrocarbons) that are
conjugated by UGT1A1, although the results also imply that such
individuals may also may have greater opportunity to decrease
that risk through dietary intervention. (J Nutr. 2005;135:1051-5).
Reproductive and Developmental Toxicology Research Core
(RC3)
Investigators
in the Reproductive and Developmental
Toxicology Research Core (RC3) are interested in how
environmental factors impact human reproduction and development.
For
example, Elaine Faustman (RC3
Director) is interested in understanding the molecular mechanisms
by which exposure to the environmental pollutant, arsenite
(As(3+)) during development causes neural tube defects and
other structural malformations, and with behavioral alterations
including altered locomotor activity and operant learning.
Because arsenic can cross the placenta and accumulate in the
developing neuroepithelium, they examined cell cycling effects
of sodium arsenite (As(3+) 0, 0.5, 1, 2, and 4 muM) on embryonic
primary rat midbrain (gestational day [GD] 12) neuroepithelial
cells over 48 h. The researchers observed a time- and concentration-dependent
inhibition of cell cycle progression as early as 12 h after
exposure. They also found a concentration-dependent increase
in cytostasis within all cell cycle phases, a decreased proportion
of cells able to reach the second cell cycle, and a reduced
cell cycle entry from gap 1 phase (G(1)). These data support
a role for perturbed cell cycle progression in As(3+) mediated
neurodevelopmental toxicity. (Toxicol Sci. 2006
Feb;89(2):475-484. Epub Oct 2005)
Neurotoxicology Research Core (RC4)
Investigators
in the Neurotoxicology Research Core (RC4) have
had a long-standing interest in identifying and understanding
gene-environment interactions important in the development of
chronic neurodegenerative diseases such as Parkinson’s
Disease.
In
the past year CEEH investigators Harvey Checkoway,
Lucio Costa (RC4 Director), and affiliate
member William Longstregth, have completed
both epidemiological and laboratory-based studies to further
explore the hypothesis that pesticide exposure can be a risk
factor for PD or other neurological diseases. For example, they
examined two hundred fifty incident PD case patients and 388
healthy control subjects (age- and sex-matched) for possible
association with pesticide exposures, as assessed by self-reported
pesticide exposures using a structured interview. Odds ratios
for occupational exposures were not significant but suggested
a gradient that paralleled occupational exposures (pesticide
worker: OR, 2.07; 95% CI, 0.67-6.38; crop farmer: OR, 1.65; 95%
CI, 0.84-3.27; animal and crop farmer: OR, 1.10; 95% CI, 0.60-2.00;
and dairy farmer: OR, 0.88; 95% CI, 0.46-1.70). Odds ratios for
organophosphates paralleled the World Health Organization hazard
classifications, with parathion much higher than diazinon or
malathion. They also found elevated, but not statistically significant
ORs from herbicides (OR, 1.41; 95% CI, 0.51-3.88) and paraquat
(OR, 1.67; 95% CI, 0.22-12.76).They found no evidence of risk
from home-based pesticide exposures, but did find significantly
increased ORs from lifelong well water consumption (OR, 1.81;
95% CI, 1.02-3.21). They concluded that the findings for occupational
pesticide exposures are consistent with a growing body of information
linking pesticide exposures with PD. However, the lack of significant
associations, absence of associations with home-based exposures,
and weak associations with rural exposures suggest that pesticides
did not play a substantial etiologic role in this population.
(Arch Neurol. 2005;62:91-5).
In
a different study (Neurosci Lett. 2005;375:178-80), these investigators
utilized the Functional
Genomics Core to examine
associations of genetic polymorphisms of NQO1 (C609T) and NQO2
(I/D, 29 base pairs) with PD in a population-based case-control
study of 190 idiopathic PD cases and 305 unrelated controls matched
on age and sex. No associations were detected for either gene variant
or for any allele combinations.
Working
on the same hypothesis in the laboratory, Costa and Checkoway collaborated
to examine whether genetic polymorphisms in the dopamine transporter
(DAT) might be important to a number of dopamine-related neurological
disorders, including Parkinson's disease. The coding region of
the DAT gene, SLC6A3, is well conserved, but non-coding regions
are more variable, most notably a variable number of tandem repeats
(VNTR) polymorphism in the 3' untranslated region. They examined
variation in the 5' region of SLC6A3 because little is known
about the extent of variation in this region and potential consequences
of such variation on gene expression. With the aide of the Functional
Genomics Facility Core, they identified multiple single
nucleotide polymorphisms (SNPs) covering approximately 5000 bp
5' of exon 1 through the start of exon 2 (+2106). These SNPs
segregated as eight haplotypes, six of which were common. These
haplotypes differed significantly in activity in a reporter gene
activity assay. However, they did not observe associations between
common SNPs or haplotypes and PD in a case-control study of 261
incident cases and 376 age- and gender-matched unrelated controls.
However, they did observe a modest association of the 3' VNTR
9-repeat allele with PD (odds ratio=1.45; 95% confidence interval=1.04-2.03).
This association was limited to subjects 60 years of age and
greater versus those less than 60 years of age. They concluded
that although DAT 5' region SNPs haplotypes significantly alter
in vitro transcriptional activity, they are not related to PD
risk. Their results do provide further evidence supporting an
association of PD with the VNTR polymorphism. (Pharmacogenet
Genomics. 2005 (9):659-68).
In
a different collaboration, Anneclaire
De Roos (Carcinogenesis
Research Core) and Checkoway utilized the Functional
Genomics Facility Core to evaluate whether a genetic
polymorphism in the enzyme, paraoxonase, might be associated
with childhood risk of brain tumors. Prior research suggests
that childhood brain tumors (CBTs) may be associated with exposure
to pesticides. Organophosphorus insecticides (OPs) target the
developing nervous system, and until recently, the most common
residential insecticides were chlorpyrifos and diazinon, two
OPs metabolized in the body through the cytochrome P450/paraoxonase
1 (PON1) pathway. To investigate whether two common PON1 polymorphisms,
C-108T and Q192R, are associated with CBT occurrence, De Roos
and Checkoway conducted a population-based study of 66 cases
and 236 controls using DNA from neonatal screening archive specimens
in Washington State, linked to interview data. The risk of CBT
was nonsignificantly increased in relation to the inefficient
PON1 promoter allele [per PON1(-108T) allele, relative to PON1(-108CC):
odds ratio (OR) = 1.4; 95% confidence interval (CI), 1.0-2.2;
p-value for trend = 0.07]. Notably, this association was strongest
and statistically significant among children whose mothers reported
chemical treatment of the home for pests during pregnancy or
childhood (per PON1(-108T) allele: among exposed, OR = 2.6; 95%
CI, 1.2-5.5; among unexposed, OR = 0.9; 95% CI, 0.5-1.6) and
for primitive neuroectodermal tumors (per PON1(-108T) allele:
OR = 2.4; 95% CI, 1.1-5.4). The Q192R polymorphism, which alters
the structure of PON1 and influences enzyme activity in a substrate-dependent
manner, was not associated with CBT risk, nor was the PON1(C-108T/Q192R)
haplotype. These results are consistent with an inverse association
between PON1 levels and CBT occurrence, perhaps because of PON1's
ability to detoxify OPs common in children's environments. Larger
studies that measure plasma PON1 levels and incorporate more
accurate estimates of pesticide exposure will be required to
confirm these observations (Environ Health Perspect.
2005;113:909-13).
Finally, Costa and Clem
Furlong continued
their long-standing and productive collaboration to evaluate
the significance molecular implications of the PON1 polymorphism,
including: the measurement of paraoxonase (PON1) status as a
potential biomarker of susceptibility to organophosphate toxicity
(Clin Chim Acta. 2005 Feb;352(1-2):37-47); how various environmental
factors, (i.e., drugs, smoking, alcohol, diet, age, disease conditions)
modulate PON1 activity (Biochem Pharmacol. 2005 Feb 15;69(4):541-50);
how transgenic models of PON1 can be used to predict potential
human susceptibility to PON1 substrates such as chlorpyrifos
(Pharmacogenet Genomics. 2005;15:589-598); and the importance
of age/developmental status in PON1-mediated differences in susceptibility
to pesticides (Neurotoxicology2005; 26:651-9).
Cardiovascular and Respiratory Toxicology Research Core
(RC5)
The Cardiovascular and Respiratory Toxicology Research
Core (RC5) consists of a group of investigators with
interests in how environmental factors, especially airborne
particulate matter, effects both cardiovascular and respiratory
health. For example Jane Koenig (RC5 Co-Director), Joel
Kaufman (RC5 Director), affiliate member Lianne
Shepard, and collaborators have evaluated the health effects
of airborne particulates from several perspectives.
In
one study, the researchers measured fractional exhaled nitric
oxide (FE(NO)), spirometry, blood pressure, oxygen saturation
of the blood (SaO2), and pulse rate in 16 older subjects with
asthma or chronic obstructive pulmonary disease (COPD) in Seattle,
Washington. Data were collected daily for 12 days. The researchers
simultaneously collected PM10 and PM2.5 on filter samples at
a central outdoor site, as well as outside and inside the subjects'
homes. The researchers also collected samples from personal PM10
filters. All filters were analyzed for mass and light absorbance.
We analyzed within-subject associations between health outcomes
and air pollution metrics using a linear mixed-effects model
with random intercept, controlling for age, ambient relative
humidity, and ambient temperature. For the 7 subjects with asthma,
a 10 microg/m3 increase in 24-hr average outdoor PM10 and PM2.5
was associated with a 5.9 [95% confidence interval (CI), 2.9-8.9]
and 4.2 ppb (95% CI, 1.3-7.1) increase in FE(NO), respectively.
A 1 microg/m3 increase in outdoor, indoor, and personal black
carbon (BC) was associated with increases in FE(NO) of 2.3 ppb
(95% CI, 1.1-3.6), 4.0 ppb (95% CI, 2.0-5.9), and 1.2 ppb (95%
CI, 0.2-2.2), respectively. No significant association was found
between PM or BC measures and changes in spirometry, blood pressure,
pulse rate, or SaO2 in these subjects. Results from this study
indicate that FE(NO) may be a more sensitive marker of PM exposure
than traditional health outcomes and that particle-associated
BC is useful for examining associations between primary combustion
constituents of PM and health outcomes. (Environ Health Perspect.
2005;113:1741-6).
Koenig,
Kaufman, and Shepard are also studying a cohort of 19 children
with asthma living in Seattle. In one study of the impacts of
particulate air pollution on children, Koenig and
collaborators evaluated the differential health effects of indoor-
and ambient-generated particles. They combined their recursive
model and a predictive model for estimating infiltration efficiency
to separate personal exposure (E) to PM2.5 (PM with aerodynamic
diameter < or = 2.5 microm) into its indoor-generated (Eig)
and ambient-generated (Eag) components for 19 children with asthma.
They then compared Eig and Eag to changes in exhaled nitric oxide
(eNO), a marker of airway inflammation. Based on the recursive
model with a sample size of eight children, Eag was marginally
associated with increases in eNO [5.6 ppb per 10-microg/m3 increase
in PM2.5; 95% confidence interval (CI), -0.6 to 11.9; p = 0.08].
Eig was not associated with eNO (-0.19 ppb change per 10 microg/m3).
Their predictive model allowed them to estimate Eag and Eig for
all 19 children. For those combined estimates, only Eag was significantly
associated with an increase in eNO. Effects were seen only in
children who were not using corticosteroid therapy. They concluded
that the ambient-generated component of PM2.5 exposure is consistently
associated with increases in eNO and the indoor-generated component
is less strongly associated with eNO. (Environ Health Perspect.
2005;113:499-503).
A
second study of these children evaluated associations between
short-term (hourly) exposures to particulate matter with aerodynamic
diameters < 2.5 microm (PM2.5) and the fractional concentration
of nitric oxide in exhaled breath (FE(NO). The researchers used
a polynomial distributed lag model to assess the association
between hourly lags in PM2.5 exposure and FE(NO) levels. Their
model controlled for age, ambient NO levels, temperature, relative
humidity, and modification by use of inhaled corticosteroids.
They found that FE(NO) was associated with hourly averages of
PM2.5 up to 10-12 hr after exposure. Their data provide new information
concerning the lag structure between PM2.5 exposure and a respiratory
health outcome in children with asthma. (Environ Health Perspect.
2005;113:1791-4).
In
another population-based study, Koenig and Kaufman conducted
a study to determine relationships between various measures of
air pollution and cardiorespiratory effects in older subjects.
Past studies of air pollution effects among sensitive subgroups
have produced inconsistent results. Their study design included
repeated measurements of pulmonary function (arterial oxygen
saturation) and cardiac function (heart rate and blood pressure)
in a panel of 88 subjects (>57 years of age) in Seattle during
the years 1999 to 2001. Subjects were healthy or had lung or
heart disease. Each subject participated in sessions of 10 consecutive
days of exposure monitoring and collection of health outcomes
for up to 2 sessions. Associations between health outcomes and
indoor, outdoor, and personal measures of particulate matter </=2.5
micrometers (PM2.5) or particulate matter </=10 micrometers
(PM10) were evaluated using generalized estimating equations
with an exchangeable working correlation matrix and robust standard
errors. The model included terms for the within-subject, within-session
effect; the within-subject, between-session effect; and an interaction
term for medication usage. Associations between air pollution
and health measurements were found primarily in healthy subjects.
Healthy subjects taking no medications had decreases in heart
rate associated with indoor and outdoor PM2.5 and PM10. Healthy
subjects on medication had small increases in systolic blood
pressure associated with indoor PM2.5 and outdoor PM10. Heterogeneity
analysis found differences among the health groups for associations
with particulate air pollution in heart rate but not in blood
pressure. From their results they concluded that modest concentrations
of air pollutants were associated with small changes in cardiac
function. (Epidemiology. 2005; 16:681-7).
Biostatistics and Biostatistical Methodologies Research
Core (RC6)
The Biostatistics and Biostatistical Methodologies Research
Core (RC6) includes CEEH investigators interested
in developing and applying new computational approaches to
the analysis of toxicogenomics data. Although the Core was
brand new in 2005, a few publications have already resulted
from collaborations between RC6 investigators and others CEEH
faculty. For example, Roger Bumgarner, Kathleen
Kerr, and Zarbl—along with
Theo Bammler, Richard Beyer, and Federico Farin, research scientists
from the Bioinformatics and Biostatistics Facility Core--were
key contributors to a Nature Methods paper from the
NIEHS Toxicogenomics Consortium. This group of investigators
from 7 different research programs across the country conducted
parallel microarray experiments to identify sources of error
and data variability between laboratories and across microarray
platforms, and then constructed methods to accommodate this
variability. RNA expression data were generated in seven laboratories,
which compared two standard RNA samples using 12 microarray
platforms. At least two standard microarray types (one spotted,
one commercial) were used by all laboratories. Reproducibility
for most platforms within any laboratory was typically good,
but reproducibility between platforms and across laboratories
was generally poor. Reproducibility between laboratories increased
markedly when standardized protocols were implemented for RNA
labeling, hybridization, microarray processing, data acquisition
and data normalization. Reproducibility was highest when analysis
was based on biological themes defined by enriched Gene Ontology
(GO) categories. These findings indicate that microarray results
can be comparable across multiple laboratories, especially
when a common platform and set of procedures are used. (Nat
Methods. 20052:351-6).
Major
Outreach Accomplishments
DNA, Health and Social Justice: A Forum on Community
Genetics held in Seattle, WA, in May 2005
In 2005, the CEEH Community Outreach and Education Program
(COEP) worked closely with the Ethical Legal and Social Implications
Core, the UW Center for Genomics and Healthcare Equality, and
the Institute for Public Health Genetics on the Community Genetics
Forum. The two major goals for the Forum were to share with the
public the promises and challenges of genomics, and to highlight
the breadth of research career opportunities in genomics. Community
advisors provided input on shaping the content and tone of the
plenary and breakout sessions. Community advisors also expanded
the Forum’s reach to include diverse community-based organizations
and extended personal invitations to their constituents.
Almost three hundred attendees had an opportunity to learn and
talk about current topics in genetics such as uses of genetics
in health care, DNA-based ancestry testing, and careers in genetics.
Participants included high school teachers, high school students,
UW students, community members, and academics. The morning session
opened with a student presentation, followed by a keynote address
by Francis Collins, director of the National Human Genome Research
Institute (NHGRI). This transitioned into responses from a panel
of community leaders and an open question and answer period.
After this plenary session, participants attended concurrent
breakout sessions. At the end of the day, participants reconvened
as a whole to comment and hear from Collins.
Participants
were asked to fill out evaluation surveys at each breakout session
they attended as well as for the overall Forum. Additionally,
student note-takers took handwritten notes on the session discussions,
as close to verbatim as possible. These notes were used with the
quantitative survey results to capture the themes of the discussions.
The Forum showed that scientific and community agendas can be negotiated
to produce common understanding and to identify common priorities.
Participants were looking for answers to tough questions about
controversial topics such as race and genetics, and genes and the
environment. Many participants suggested that the dialogue should
continue, especially in smaller groups throughout different communities.
UW faculty and the NHGRI have committed to being a resource for
those who want more information on these topics, and will be organizing
smaller listening sessions in the future.
Grant
number P30-ES07033, from the National Institute of Environmental
Health Sciences, NIH, and P50-HG03374 NHGRI ELSI Center of Excellence:
Genomic Health Cares and the Medically Underserved from the National
Human Genome Research Institute supported this project
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