Investigator's Name, Title

Address

1\. [TITLE:]{.underline} "Title"

2\. [RELATED PROJECTS]{.underline}: *List all related projects,
including both those from collaborating institutions and local
approvals.*

3\. [NATURE & PURPOSE]{.underline}: *Provide a brief summary of the
proposed research, i.e.:* The prevalence of coronary artery disease
(CAD) continues to increase in North America and remains a major health
concern. Many major cardiovascular disease events occur in patients
without any previously diagnosed risk factors, and one-third of all
cardiovascular disease events now occur in individuals under the age of
65. Early identification of high-risk individuals who may benefit from
prevention programs is an important strategy for decreasing CAD
mortality.

*Describe Berkeley Lab's role in the research, i.e.*: This collaborative
project will study candidate genes for mutations that may explain a
subset of CAD cases. The goal is to identify DNA sequence variations
that predispose individuals to early CAD. Berkeley Lab's part in this
research will be limited to the genomic analysis of samples collected
under:

McDOUGAL, R., MD "Genetic Risk Factors for Coronary Heart Disease" #UOHI
05-555, University of Ottawa, Ottawa; Ontario, Canada

This protocol was approved May 20, 2004; Expiration: May 20, 2005

McAULIFFE, R. MD "UCSF Comprehensive CAD Tissue Bank"

H5005-50555-05

This protocol was approved April 20, 2004; Expiration: April 20, 2005

McCRACKEN, R., PhD "More Genetic Risk Factors for Coronary Heart
Disease" #OPHS 2003-05-5555

This protocol was approved April 20, 2004; Expiration: April 20, 2005

*For institutions other than Berkeley Lab or UCB, provide assurance of
compliance information, i.e.*: The University of Ottawa holds
federal-wide assurance of compliance #A00003664 from the United States
Public Health Service's Office for Human Research Protections (OHRP).
The University of California, San Francisco holds federal-wide assurance
of compliance #A00000068 from the OHRP.

4\. [SUBJECTS]{.underline}: Berkeley Lab will receive approximately 2500
samples each year.

All subject interaction will take place under the local University of
Ottawa, UCSF or University of California at Berkeley (UCB) protocols.
Ottawa subjects will include 1000 male and female out-patient subjects,
age 18-80 years, with a diagnosis of CAD before the age of 65; and 1000
male and female age and sex-matched normal controls. UCSF subjects will
include 1000 CAD patients who consent to having a small blood sample
banked for future research. Berkeley subjects will include 500
age-matched controls recruited through newspaper advertisement.

5\. [RECRUITMENT]{.underline}: Not applicable; no local recruitment of
subjects.

6\. [SCREENING PROCEDURES]{.underline}: Not applicable; no local
recruitment of subjects.

7\. [RESEARCH PROCEDURES]{.underline}: *Describe Berkeley Lab's
involvement in the research, including exactly what kinds of samples
and/or data will be received, and what information will be returned to
the collaborating institution and, if applicable, whether the
information will be used to guide treatment and/or shared with the
subjects*. Berkeley Lab's part in this research will be limited to the
genomic analysis of coded DNA obtained from blood samples collected by
the Ottawa, UCSF and Berkeley collaborators. LBNL will also receive data
identifying the subject's gender, age, weight and blood pressure.

The Ottawa, UCSF and Berkeley protocols call for the collection of a
single 20 ml fasting blood sample from each subject. Subjects will also
be asked to give a complete health history and have their height,
weight, and blood pressure measured.

The results of the Berkeley Lab analysis will be shared with the
collaborating researchers at the institutions where the samples were
collected. The results will not be used to guide treatment. The
individual results of the Berkeley Lab analysis will be shared with the
subjects from Ottawa as specified in that institution's protocol and
consent form. Individual results will not be shared with the subjects
from UCSF or UCB.

8\. [BENEFITS]{.underline}: There is no direct benefit to the subjects.
Benefits to society may include better methods for early assessment of
cardiac disease risk.

9\. [RISKS]{.underline}: Risks associated with the collection of small
quantities of blood include local discomfort, bruising, and a slight
chance of infection. The risks to the Ottawa, UCSF and Berkeley subjects
are not increased by the involvement of Berkeley Lab researchers in the
analysis phase of the project.

10\. [CONFIDENTIALITY]{.underline}: Samples will be coded before their
shipment to Berkeley Lab, and the Berkeley Lab team will not have access
to either the code key or any identifying information about the
subjects.

11\. [INFORMED CONSENT]{.underline}: Subjects are consented at the
University of Ottawa, UCSF, or the University of California at Berkeley.
and are specifically told of the DNA analysis. Please accept the local
consent forms as approved.

*Optional language on waiver of standard consent format*: Use of the
collaborating institution's consent form may constitute a waiver or
alteration of the UCB-Berkeley Lab Committee for Protection of Human
Subjects standard consent form language. A waiver is justified in this
instance because:

\--The research is minimal risk;

\--The waiver would not affect the rights and welfare of the subjects,
since they have already knowingly consented to participate in a format
meeting the criteria of their locale; and

\--The research cannot be practicably carried out without the waiver.

12\. [FINANCIAL ASPECTS]{.underline}: Not applicable.

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13\. [WRITTEN MATERIALS]{.underline}: Attached are copies of the
protocol and consent forms from the University of Ottawa and the
University of California at Berkeley and proof of approval from the
respective Institutional Review Boards.