NIAMS ADMINISTRATIVE SUPPLEMENTS TO INCREASE REPRESENTATION OF MUSCULOSKELETAL 
TISSUES AND SKIN IN CDNA DATABASES

Release Date:  October 3, 2000

NOTICE:  AR-01-001

National Institute of Arthritis and Musculoskeletal and Skin Diseases

The National Institute of Arthritis and Musculoskeletal and Skin Diseases 
(NIAMS) announces the availability of administrative supplements to enable 
investigators currently supported by the NIAMS to contribute tissue samples 
and RNA preparations from musculoskeletal tissues and skin for analysis in on-
going NIH-supported cDNA cloning and sequencing efforts.  Increasing the 
representation of musculoskeletal tissues and skin in publicly accessible cDNA 
sequence databases such as the Cancer Genome Anatomy Project (CGAP) will 
facilitate the design of gene expression experiments in these tissues and may 
identify novel genes that are expressed at negligible or very low levels in 
other tissues.  This announcement addresses a need identified in the NIAMS 
Strategic Plan (http://www.nih.gov/niams/strategicplan/index.htm).

Many thousands of cDNAs have been cloned and sequenced to date.  The results 
of these efforts have been incorporated into several public databases, such as 
CGAP (http://www.ncbi.nlm.nih.gov/CGAP/), dbEST (http://www.ncbi.nlm.nih.gov/dbEST/), 
and UniGene (http://www.ncbi.nlm.nih.gov/UniGene/).  Individual clones may be 
ordered from the I.M.A.G.E. Consortium at http://image.llnl.gov/.  However, 
these resources consist chiefly of clones derived from intensively studied human 
tissues such as breast and prostate.  While many of the genes represented by 
existing clones are undoubtedly expressed in musculoskeletal tissues and skin, 
there is little to indicate which genes should be included in analyses of these 
tissues.  Further, it is likely that a significant number of genes are 
expressed predominantly or exclusively in specific musculoskeletal tissues and 
skin, and hence would not be represented in libraries prepared from other 
tissues.  Finally, biological studies employing the mouse will require cDNA 
resources from mouse tissues, which are currently less well represented than 
human tissues.

The NIAMS has entered into an agreement with the National Cancer Institute to 
enable investigators with expertise in handling musculoskeletal tissues and 
skin to submit tissue samples or RNA preparations to laboratories specializing 
in the construction of libraries and high-throughput cloning and sequencing.  
Principal Investigators of currently active NIAMS grants may request 
administrative supplements to cover the costs of preparing and submitting 
tissues or RNA for analysis under this agreement.  The grant award to be 
supplemented must have at least one full year of originally obligated support 
remaining from the date of the supplement request.  The cells or tissues 
proposed as a source of RNA  must be in use in the investigator=s laboratory 
as part of on-going NIAMS-supported research.  Investigators who propose to 
submit samples originating with human subjects are responsible for ensuring 
that informed consent for this use of tissue has been appropriately 
documented.

RNA sources of interest include, but are not restricted to: primary cell 
cultures from bone, cartilage (growth plate and articular), synovium, tendon, 
ligament, skeletal muscle, and skin; established cell lines that exhibit 
properties of differentiated tissues such as those listed above; and tissue 
specimens representing biologically defined cell aggregates, such as zones of 
the growth plate, fracture callus, or pathological states of musculoskeletal 
tissues and skin.  Samples may be from either human or mouse.  In general, 
intact cells or tissues are preferred, so that RNA isolation procedures 
optimized for library construction may be used.  However, investigators having 
experience with specialized techniques for recovering RNA from connective 
tissues that are refractory to standard methods may propose to submit RNA 
isolated by these specialized techniques.  Library construction usually 
requires approximately one gram of tissue or three micrograms of purified RNA. 
 Each library prepared from submitted material will carry a unique identifier 
under which resulting sequence data may be retrieved from the CGAP database.  
Sequenced clones will be made available through the I.M.A.G.E. Consortium.  

Requests for supplements should be submitted in the form of a letter, signed 
by the investigator and by an authorized institutional official, which 
contains the following information:

o  the title and identifying number of the grant that currently supports work 
with the cell or tissue source(s)

o  a description of the proposed cell or tissue source(s), noting the 
relationship to the NIAMS-supported research project, and addressing the 
question of informed consent if it is proposed to transfer samples originating 
with human subjects

o  a brief summary of the biological significance of the source(s)

o  a description of the methodology to be employed in preparing the sample(s), 
including standards that will be applied for the purity of RNA preparations

o  the number of cells, wet weight of tissue, or amount of RNA expected to be 
available from each source

o  the amount of supplemental funding requested

o  a brief summary of how the supplemental funds will be used.

Requests will be reviewed by a committee of NIH staff and non-government 
scientists.  The committee will consider the significance of the source 
(including the availability of sequences from similar sources already in the 
database), the adequacy of the methodology proposed for sample preparation, 
and the cost of the proposed supplement.  It is expected that most supplements 
awarded for this purpose will be less than $10,000 direct costs.  Requests for 
supplements greater than $10,000 direct costs must be rigorously justified.  
Requests should anticipate costs associated with express shipping of 
biological materials within the United States.  Investigators whose requests 
are approved will be contacted at a later date regarding the details of 
transferring samples.  

Requests for supplements must be received before August 1, 2001.  Requests 
should be sent to:

William J. Sharrock, Ph.D.
Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-37A
45 Center Drive
Bethesda, MD 20892-6500

Inquiries regarding programmatic issues should be directed to:

William J. Sharrock, Ph.D.
Extramural Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5AS-37A
45 Center Drive
Bethesda, MD 20892-6500
Phone: 301-594-5055
Fax: 301-480-4543
e-mail: ws19h@nih.gov

Inquiries regarding fiscal matters should be directed to:

Melinda B. Nelson
Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-49F, MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-3535
FAX:  (301) 480-5450
Email:  mn23z@nih.gov


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