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The
Chronology
1985
- The National
Center for Research
Resources (NCRR),
NIH, Research Centers
in Minority Institutions
(RCMI) Interdisciplinary
Program provided sustained
core support for establishment
of the Human Immunogenetics
Laboratory, the foundation
for the human genome
research initiative
at Howard University.
The
Immunogenetics laboratory
was established in
1985 under the direction
of Dr. Georgia M.
Dunston. It has been
continuously funded
as a national resource
to conduct and facilitate
research on the characterization
of human leukocyte
antigen (HLA) polymorphisms
in African Americans
and the biomedical
significance of HLA
polymorphisms in African
Americans.
As the most polymorphic
system of expressed
human genes known,
HLA research has been
a microcosm of the
macrocosm of genome-wide
studies catalyzed
by the Human Genome
Project. HLA research
has been instructive
for human genome research
in the use of polymorphic
markers to map genes
for disease susceptibility;
to explore population-based
variation in linkage
disequilibrium of
HLA genes, and raising
questions about ethical,
legal, and social
issues surrounding
ethnic disparities
in tissue matching
for clinical transplantation
and long term survival
of organ transplants.
For approximately
10 yrs, (1982-93)
Dr.
Dunston and the
Immunogenetics Laboratory
group collaborated
with investigators
at Georgetown University
(GTU) on a National
Institute of Allergy
and Infectious Diseases
contract for screening,
characterization and
acquisition of reagents
for better histocompatibility
testing of transplantation
antigens of blacks.
During this time,
local African American
families and unrelated
donors were recruited
for the GTU/HU African-American
reference lymphocyte
panel, an adjunct
to the GTU reference
lymphocyte panel.
Approximately 25%
of the panel cells
were from African
Americans recruited
largely from Howard
University faculty,
staff, students, and
friends. Cells from
African Americans
were characterized
using cDNA sequencing,
RFLP analysis, T-cell
clone analysis, and
sequence specific
oligonucleotide probe
typing. Human leukocyte
antigen (HLA) diversity
in African Americans
was not well defined
at the beginning of
the GTU/HU collaboration.
Initially 44% of the
AfricanAmerican panel,
compared to only 2%
of Caucasians, could
not be HLA-D typed
with reference typing
reagents obtained
primarily from multiparous
Caucasian women. The
African-American panel
was thus a valuable
resource for research
collaborations on
the molecular characterization
of undefined HLA-Class
II antigens. Substantial
progress was made
during this time in
the characterization
of multiple new variants
of DR and DQ alleles
and unique HLA haplotypes.
1990
- 1993- In September
1990, Howard University
(PI: Demenais F; Bonney
GB; Dunston GM; Adams-Campbell
L) received a grant
from the National
Cancer Institute (NCI)
entitled, Gene and
Environmental Interactions,
a genetic epidemiology
study designed to
yield data useful
in the identification
of breast cancer susceptibility
genes in the target
population. From its
initial focus on the
characterization of
genomic variation
in the HLA system
in African Americans
and HLA associations
with disease susceptibilities,
in 1990 the Human
Immunogenetics Laboratory
was expanded to serve
as a core resource
for processing, systematic
storage, and retrieval
of cells and DNA for
the collaborative
genetic epidemiology
of breast cancer project.
The advent of the
U.S. Human Genome
Project (HGP) in 1990
focused attention
on the construction
of comprehensive genetic
maps for locating
and identifying genes
underlying susceptibility
to disease. Two major
catalysts were recognized
as significant to
the rapid success
of the HGP in the
construction of genetic
maps:
1) the discovery of
polymorphic microsatellite
markers widely distributed
throughout the genome,
and 2) the availability
of the CEPH reference
family panel, a shared
resource of 67 Caucasian
families for scientific
collaboration. Based
on our knowledge of
population differences
between Caucasian
and African American
populations in HLA
polymorphisms and
knowing that genetic
distances between
population groups
influence the spectrum
of DNA polymorphisms,
investigators at Howard
University were concerned
about the applicability
of DNA marker polymorphisms
in Caucasians for
mapping genes in African
Americans and other
people of African
ancestry.
1991
- 1994-
Dr.
Dunston and colleagues
received a Planning
Grant for a proposal
on Genomic Research
in African-American
Pedigrees Project
(G-RAP) from the National
Center for Human Genome
Research (renamed
the National Human
Genome Research Institute
in 1997), funded as
a Supplement to the
Immunogenetics Laboratory
component of the RCMI
Program. The goal
of G-RAP was to broaden
the base of national
resources needed to
conduct and better
understand population
based genome variability
in African-Americans
and its applications
in mapping, identifying,
and characterizing
disease susceptibility
genes. Modeled after
resources for the
HGP, G-RAP was composed
of four interrelated
components: 1) a reference
family panel complementary
to the CEPH panel,
but representative
of genome variability
in African-Americans;
2) a human genome
reference resource
laboratory for central
receiving processing;
genomic characterization
of a core marker set
on biological specimens;
maintenance, quality
control, and storage
of reference resources,
3) a data management
and informatics core,
and 4) scientific
utilization of G-RAP
core resources.
1995
- 1996-
The report of the
first breast cancer
susceptibility gene
(BRCA1) in 1994 and
the announcement of
the new Visiting Investigator's
Program (VIP) at NEGRI
were instrumental
in Dr. Dunston taking
a sabbatical to go
to the NEGRI to study
BRCAI Mutations in
a cohort of African
American breast cancer
patients in the breast
cancer in black women
study: gene and environment
interactions. This
sabbatical provided
opportunities to develop
plans for collaborative
research projects
with NEGRI. The first
of these focused on
the genetics of type
2 diabetes in West
African ancestral
populations of African
Americans. Because
of the high frequency
of environmental risk
factors for diabetes
in the African American
population, it was
deemed more effective
to study genetic risk
factors for type 2
diabetes in West African
diabetic patients.
In the spring of 1995
a meeting was held
at NIH to discuss
the feasibility of
studying the genetics
of type 2 diabetes
in west Africans.
Following that meeting,
HU and the NEGRI designed
an affected sib-pair
linkage study and
sought competitive
applications from
west African diabetologists.
A peer-review process
was used to establish
recruitment sites
for this study. Five
sites were selected,
three in Nigeria and
two in Ghana. Because
there were concerns
about the logistical
problems involved
in doing a study of
this type in west
Africa, the study
was planned in two
stages.
An
initial one-year pilot
study preceded plans
for the follow-up
full-scale study.
Subsequent to initiation
of the type 2 diabetes,
HU and NEGRI initiated
plans to collaborate
in a national study
on hereditary prostate
cancer in African
Americans. The latter
included Dr. Francis
Collins and NEGRI
investigators, Drs.
Kate Berg; Dr. John
Carpten, and Dr. Jeffrey
Trent. Both the international
collaboration on the
genetics of type 2
diabetes in west Africans
and the national African
American hereditary
prostate cancer study
were implemented through
the partnership of
NEGRI director Dr.
Francis Collins with
Dr. John Ruffin, Director
of the NIH Office
of Research on Minority
Health (ORMH).
The three projects
on the genetics of
breast cancer, prostate
cancer, and type 2
diabetes formed the
scientific core for
the initiation of
an interinstitutional
research collaboration
between investigators
at the NEGRI and HU
that has been foundational
to the continued development
of the human genome
research program at
Howard University
and the formation
of the National Human
Genome Center at Howard
University to focus
on the genetics of
diseases common in
African Americans
and sub-Saharan west
African ancestral
populations.
1996-1997-
Howard University
received a Supplement
to Minority International
Research Training
Grant (PI: Adams-Campbell
L) funded by the ORMH
to initiate pilot
project with west
African medical scientists
to map genes for type
2 diabetes. Dr. Charles
Rotimi, genetic epidemiologist
at Loyola University
in Chicago, IL with
research expertise
in implementing large
scale collaborative
research projects
in west African was
recruited to serve
as PI, of this project.
The goal of the pilot
project was to assess
the ability of the
west African sites
to recruit appropriate
patients and collect
blood, urine and other
clinical data and
successfully ship
samples and send data
to the U.S. for genetic
analyses. Each of
the five sites successfully
completed the recruitment
of 15 sib pairs and
shipped biological
specimens to Howard
University, the coordinating
center for this international
collaboration.
1997
- 1999-
Howard University
received a Construction
Grant from NCRR with
matching funds from
the University to
renovate space on
the sixth floor of
the Cancer Center
for Human Genome Research
Center. Howard University
also received Contract
from NHGRI with major
funding from Dr. Ruffin,
ORMH, to be the Coordinating
Center for the African
American Hereditary
Prostate Cancer (AAHPC)
Study Network (PI
Dunston G). Dr. Rick
Kittles was recruited
to the position of
project director of
the AAHPC study. Plans
were implemented to
set-up a national
network of AAHPC Collaborative
Recruitment Centers
(CRCs) led by a consortium
of predominantly African-American
medical scientists
in seven urban areas:
Detroit, MI (Powell
I); New York, NY (Hoke
G); Chicago. IL (Vijayakumar
S); Atlanta, GA (Bennett
J); Houston TX (Pettaway
C); Columbia SC (Weinrich
S), and Washington
DC (McLeod).
The AAHPC is a linkage
study of hereditary
prostate cancer. The
aim is to enroll 100
families with prostate
cancer in which at
least four men are
affected in each family
and there are four
other (unaffected)
relatives are available
for the study. Blood
samples and clinical
data obtained by the
CRCs are sent to the
coordinating center.
DNA from these families
will be studied to
determine if there
is linkage to a known
hereditary prostate
cancer locus on chromosome
1 or other locations.
Genotyping and statistical
genetic analyses for
the AAHPC will be
done by the NHGRI.
Ad hoc Human
Genetics Advisory
Group Meeting held
at Howard University
to review NHGRI/HU
collaborative human
genome research projects
and plans for the
creation of a world-class
center at Howard University
for collaborative
human genome research
focusing on the genetics
of diseases common
in African Americans.
1998-
Howard University
received a contract
from the NHGRI with
major funding from
the ORMH to be the
coordinating center
for the genetics of
type 2 diabetes study
in west Africans.
To more appropriately
reflect the international
nature of the collaboration
and west African source
of the study group,
the name of the project
was changed to the
Africa America Diabetes
Mellitus (AADM) Study
Network.
Based on the success
of the pilot study,
the full scale study
to map genes for type
2 diabetes in west
Africans was initiated
in September, 1998
with the goal of collecting
400 affected sib pairs.
Along with the biological
specimens which include
blood and urine samples,
investigators collect
extensive epidemiological,
family history, and
medical data for this
study.
Dr.
George E. Bonney,
an internationally
recognized statistical
geneticist, was recruited
to Howard University
as Full Professor
in the Department
of Microbiology to
set-up and direct
the statistical genetics
and bioinformatics
unit in the emergent
National Human Genome
Center (NHGC). Dr.
Bonney is PI of a
RO1 grant from the
National Institute
of Aging, NIH to develop
software for genetic
epidemiology models
(G.E.Ms). Because
Dr. Bonney was recruited
to head a program
in the NHGC at Howard
University, his appointment
in the fall of 1998
marked the informal
beginning of the NHGC.
Dr.
Bonney has recruited
a very impressive
team of young scientists
and postdoctoral trainees
with expertise in
different aspects
of biostatistics,
computational systems,
and software development.
Dr. Rick Kittles rapidly
advanced to a leadership
position in the emerging
NHGC as a consequence
of the progress he
made in setting-up
the capacity at Howard
University for state-of-the-art
quality control of
PCR amplifiable high
quality DNA isolated
from AAHPC blood samples.
He interfaced directly
with the NHGRI laboratory
responsible for genotyping
these samples. In
addition to his role
as project director
of the AAHPC study
network, Dr. Kittles
was appointed Assistant
Professor in the Department
of Microbiology. He
successfully competed
for new investigator
institutional support
in addition to external
funding from the RCMI
Program for a Minority
Supplement to conduct
molecular genetic
research. Dr. Kittles'
work exploits gene
genealogy in studies
of population history
and disease associations.
He has been very instrumental
in the design of plans
for the renovation
of space on the sixth
floor of the cancer
center for the NHGC
genotyping and molecular
genetics laboratories
and is co-director
with Dr. Dunston,
director of the NHGC
molecular genetics
unit.
1999
- Dr.
Charles N. Rotimi
and Dr.
Charmaine Royal
were recruited to
fill two new positions
in the NHGC. Dr. Charles
N. Rotimi was recruited
from Loyola
University to the
position of Associate
Professor in the Department
of Microbiology and
director of genetic
epidemiology at the
NHGC. His leadership
in genetic epidemiology
provides the population
resource for cooperative
and collaborative
research with other
investigators at the
NHGC who provide complementary
expertise in molecular
genetics, statistical
genetics, and genethics.
Dr. Rotimi led the
AADM west African
team of medical scientists
in the successful
recruitment and near
completion of sample
collections, almost
one year ahead of
schedule, for the
full-scale AADM study.
Shortly
after arriving at
HU, Dr. Rotimi led
the NHGC team as PI
of a grant application
"In Search of Susceptibility
Genes for Type 2 Diabetes
in West Africa" submitted
to the NIH Center
for Inherited Disease
Research (CIDR) for
a genome-wide scan
of DNA from the AADM
samples. This application
was approved and DNA
has been prepared
and submitted to CIDR
for the genome-wide
scan.
Dr.
Charmaine Royal
was recruited to lead
in planning a research
program addressing
the ethical, legal,
and social implications
of human genome research.
Dr. Royal was recruited
to the NHGC from the
NHGRI, where she was
a postdoctoral trainee
with Dr. Kate Berg,
Director, Bioethics
and Special Populations
Research Program,
Office of the Clinical
Director, NHGRI. Dr.
Royal was recruited
to the position of
GenEthics Investigator
and appointed Assistant
Professor in the Department
of Pediatrics, Division
of Medical Genetics.
She has been actively
involved in writing
grant applications
and papers. Her research
focuses on the analysis
of psychosocial variables
associated with African
American participation
in genetic research
and services.
2000-
Dr.
Georgia M. Dunston,
acting director of
the NHGC, was invited
by President Swygert
to testify on the
HU human genome initiative
at his budget hearing
before the House Subcommittee
on Labor, Health and
Human Services, Education
and Related Agencies.
In recognition of
both the importance
and progress of human
genome research at
HU, space for expansion
of the NHGC's research
programs is included
in plans for new construction
of the interdisciplinary
science and technology
building. The latter
will be a state-of-the-art
research facility
complementing the
Louis Stokes Medical
Library that is under
construction and expected
to be completed in
2001. Groundbreaking
for the new construction
on the interdisciplinary
sciences center is
expected for 2001.
Earlier this year,
President
Swygert
invited experts in
medicine, public health,
ethics, and law to
serve on an External
Advisory Panel for
Planning the NHGC,
to review the draft
proposal and make
recommendations for
the NHGC at HU. The
Panel met at Howard
University in November
2000.
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