[rat-forum] BAC sequencing in the Rat and other model organisms

Simon Twigger simont at mcw.edu
Tue Apr 10 12:08:44 CDT 2001


>To: Research Community

>From: Rat Genome Database

>Date: April 10th, 2001


Dr. Susan Old of the NHLBI has asked that the following be posted. This

announcement constitutes an expansion of the mouse BAC sequencing

program to include the Rat and many additional organisms.


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OPPORTUNITY FOR OBTAINING DNA SEQUENCE OF REGIONS OF HIGH BIOMEDICAL

INTEREST

FROM MODEL ORGANISM GENOMES


Release Date:  March 15, 2001


NOTICE:  NOT-HG-01-002


National Human Genome Research Institute


Submission dates for 2001:  April 1, July 1 and October 1.


BACKGROUND AND PURPOSE


In January 2000, the National Institutes of Health (NIH) initiated the

NIH Mouse

BAC Sequencing Program to sequence BAC clones or contigs that were

determined to

be of high biomedical interest.  This program was limited to BACs

derived from

the DNA of only one mouse strain, C57BL/6J.  While the program has been

successful, several factors now warrant its expansion.  Scientists

conducting

research on other mouse strains or on other organisms have strongly

indicated

their interest in the expansion of the list of eligible organisms.  Many


important biomedical research projects involve organisms other than the

C57BL/6J

mouse strain.  Comparative sequence analysis is an important approach to

the

identification of candidate genes, inversions, breakpoints, and

conserved non-

coding sequences as candidates for cis-regulatory elements.  Many

biological

questions can be addressed by having the sequence of specific regions,

rather

than the complete genomic sequence of an organism.  Therefore, in an

effort to

facilitate the research interests of the larger biomedical research

community,

the NIH is expanding the NIH Mouse BAC Sequencing Program to include the


sequencing of BAC clones from all species of animals, fungi, and

eukaryotic

protists.


As in the past, there will be no cost to the investigators seeking

access to

this sequencing service; the sequencing will be done by centers that are

funded

through the Genome Sequencing Network.  As with all sequence data

generated by

the Human Genome Project, all of the sequence data generated by the NIH-


supported Genome Sequencing Network are subject to the "Bermuda Rules."

The

data will be rapidly released into GenBank; unfinished data will be

submitted

within 24 hours of generation of 2kb sequence assemblies, and finished

data as

soon as completed.  In particular, under this program of sequencing

regions of

high biomedical significance, no sequence data will be made available to

the

requestor prior to public release.   All publications using these data

must

acknowledge the publicly funded effort as their source.  In addition, if

BAC

clones that are approved for sequencing are not available commercially,

the

requestor must agree to make arrangements for the clone(s) to be

distributed,

upon request, to the scientific community in an expeditious manner.


2001 PROGRAM DESCRIPTION


The National Human Genome Research Institute (NHGRI) and its advisors,

in

collaboration with the Genome Sequencing Network, have decided to expand

the

list of organisms eligible for sequencing under the current NIH Mouse

BAC

Sequencing Program to include all animals, fungi, and eukaryotic

protists.  This

program change is intended to address the interest of the larger

biomedical

research community in obtaining sequence information about specific

regions of

genomic DNA of biomedical or biological significance.  Several of the

sequencing

centers that are participating in the Sequencing Network will dedicate a


fraction of their sequencing capacity to this initiative.


The program will continue many features of the original program.

Investigators

interested in obtaining the sequence of a specific region will submit a

short,

Web-based application describing the clone or region whose sequence is

being

requested, its importance, and its readiness to be sequenced.  A panel

of peer

reviewers will evaluate the requests and advise the NHGRI on the

priority of the

requests. Those requests judged to be of highest priority will then be

chosen by

the participating sequencing centers for inclusion in their sequencing

pipelines, subject to available capacity.


In addition to the NIH program, the Department of Energy, the Medical

Research

Council in the United Kingdom and Genoscope in France have similar

programs.

Every effort will be made to coordinate with these agencies to avoid

unnecessary

duplication of effort.


ELIGIBILITY REQUIREMENTS


Any investigator may submit a request to have one or more BAC clones

sequenced

from one or more eligible organisms (plants and prokaryotes are

excluded).

Requestors must also provide the BAC clone(s), if chosen, to the

participating

sequencing centers.


SCOPE OF REQUEST


Requests may be for half-shotgun (approximately 4-fold coverage), full

shotgun

coverage (6-10-fold coverage) or finished sequence.  Investigators

should

provide appropriate justification for the requested level of coverage.

Any BAC

sequenced from the mouse RPCI-23 library or the rat BAC library

designated for

genomic sequencing by the NHGRI Genome Sequencing Network will be

finished so

that the sequence will be maximally useful to the centers generating the


sequence of the entire genome.


PROCEDURE FOR SUBMITTING A REQUEST


Requests to have BAC clone(s) sequenced must be submitted electronically


according to the following instructions. The request form is available

at:

http://mouse.info.nih.gov.   The Web-based request must include:


1. A short description of the biomedical or biological importance of the

region

contained within the BAC clone(s) to be sequenced.


2.  Evidence that the region described is included within the identified


clone(s).


3.  In the case of a BAC contig where significant map building may have

been

done, all known underlying and overlapping clones must be identified and


evidence for the structure of the BAC contig described.


4.  Any other available information about the clone(s) such as the size

of the

region to be sequenced, paired BAC end sequences, genomic map location,

available marker information; sequence information; restriction digest

fingerprint pattern; clone instability, repeats, deletions, and problems

growing

the clone(s) and the conditions used to overcome them.


5.  Evidence that confirms that the requested region has not already

been

sequenced, and that the requested BAC is not already in the sequencing

pipeline.

Information on the status of individual BACs within the Research

Network=92s

sequencing pipelines can be found at:

http://www.ncbi.nlm.nih.gov/genome/clone/.


6.  Requestors must agree to the following terms and conditions:


(a) Data will be released according to the "Bermuda Rules" --All

sequence data

generated by the publicly funded effort will be rapidly released into

the public

domain.  Unfinished data will be released within 24 hours of generation

of 2 kb

assemblies and finished data will be released as soon as completed

(Guyer, M.

Statement on the rapid release of genomic DNA sequence.  Genome Res. 8,

413

(1998.).  No sequence data will be made available to the requestor prior

to

public release.


(b) Any publication using these data will acknowledge the source of the

DNA

sequence data using the following statement:  "The sequence data were

generated

by [name of sequencing center] through the NIH-funded Genome Sequencing

Network."


(c) If BAC clone(s) sequenced through the public effort are not

available

commercially, the requestor must agree to make arrangements for the

clone(s) to

be distributed, upon request, to the scientific community in an

expeditious

manner immediately upon publication of a research paper using any or all

of the

sequence information generated through the public effort.


The submission dates for the 2001 Program are April 1, July 1, and

October 1.

Because of the accelerated review and frequent deadlines, the submission

dates

will not be waived for any reason.



REVIEW FOR DESIGNATION AS A PRIORITY REGION


The reviews will be conducted by a panel of biologists with a broad

range of

biomedical interests.  Requests will be reviewed approximately one month

after

the submission date. The criteria for determining the relative priority

of the

requests will be:


-    biomedical or biological significance of the region contained in

the clones

identified for sequencing.  Why is this region of particular importance

to the

rapid advancement of biomedicine?  Is the genetic information in this

region of

particularly widespread relevance?  and


-   evidence that the region(s) of interest is contained in the

identified

clones.


Requests will receive one of three designations: highest priority;

moderate

priority; and declined.


All requestors will be provided with written comments addressing the

adequacy of

the request with respect to the review criteria.  Because of the rapid

review

cycle, resubmission will be the only means for re-consideration of a

request.

There will be no limit on the number of times a request for a specific

region

can be resubmitted, but each iteration will be required to contain

additional

significant information.


POST-REVIEW AND PROGRAMMATIC CONSIDERATIONS


NHGRI staff will inform all requestors of the results of the review,

approximately two weeks after the review meeting.  For those requests

that are

approved, it cannot be anticipated how many will be selected for

sequencing

because it will depend upon the available sequencing capacity, the

number of

BACs approved and the depth of coverage requested.  Highest priority for

access

to the sequencing facilities will be given to requests that make the

most

compelling reason(s) based on the anticipated significance of the

biomedical or

biology discovery.


Immediately following the review, all approved clones will be listed on

a public

Web site (http://www.ncbi.nlm.nih.gov/genome/clone/) with an indication

of the

priority recommended.  Neither the name of the investigator who

requested that

the clone(s) be sequenced nor any information about the significance of

the

region(s)contained in the clones will be given.  Once a sequencing

center has

chosen the BAC clone(s) for sequencing, that change in status will be

indicated

on the public Web site.  Clones to be sequenced will then be entered

into the

sequencing pipeline.


For those investigators whose BACS have been selected for sequencing,

the NHGRI

program staff listed below will discuss how to proceed with getting the

relevant

information to the sequencing center and will act as the contact point

for the

requestors during the remainder of the sequencing process. The

generation of

information from some BACs may be completed within three months of

entering the

sequencing pipeline but some BACs may require longer periods of time.

There may

be regions that are found to be so difficult to sequence that it will be


necessary to archive the clone until new methods for sequencing are

available.

It is expected that such clones will be rare, but in such a case, NHGRI

staff

will notify the investigator who submitted the request.   It is also

possible

that a BAC with significant overlap to the one requested, containing the


sequence of interest, will be in the sequencing pipeline prior to the

request

entering the sequencing pipeline.  In this case, NHGRI staff will

provide

information about the expected timing for the sequencing of a particular


project.  Requestors SHOULD NOT contact the sequencing centers directly

unless

program staff advises them to do so.  The sequencing centers will be

focused on

high throughput production of sequence data and should therefore be

shielded

from any unnecessary distractions.


INQUIRIES


Telephone and electronic inquiries are welcomed.


To discuss programmatic issues related to this program, please contact:


Bettie J. Graham, Ph.D.

National Human Genome Research Institute

National Institutes of Health

Telephone: (301) 496-7531

E-mail: bettie_graham at nih.gov


To discuss review issues related to this program, please contact:


Jerry Roberts, Ph.D.

National Human Genome Research Institute

National Institutes of Health

Telephone: (301) 402-0838

E-mail: jerry_roberts at nhgri.nih.gov









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