Title: NCRAD Update
1NCRAD Update
Tatiana Foroud, Ph.D. Indiana University
2Identify Appropriate Families Send Columbia a
Preliminary Pedigree Obtain samples/complete
study visits Transfer Minimal Datatset to
NCRAD Send Columbia the Sampled Pedigree
3Identify Appropriate Families
4Appropriate Families for Study
- At least 2 living siblings with LOAD (onset gt 60
years) - At least 1 other living related family member who
- Has AD (onset gt 50 years)
- Or
- Is unaffected (gt 60 years)
5Who to collect?
- Genetic analysis seeks to study the transmission
of marker alleles throughout the family. - When we can determine the inheritance of all
marker alleles unambiguously, we have the
greatest power to find genes for disease! - Unaffected individuals may be very important for
collection.
6Which are the best families?
- Families with the largest number of affected
individuals. - Strong family history suggests more genetic
effects. - Unaffected individuals in families with many
affected individuals are also very important,
particularly if they are examined clinically.
7Who to Collect
- Collect the parents in generation I, if available
- Collect all siblings in generation II (affected
and unaffected) - Collect any individuals in generation III with
memory loss - Collect any individuals in generation III gt 50
years - Query for any other affected cousins, half
siblings, aunts, uncles??
I
II
III
8Unaffected Individuals
- We focus the collection of unaffected individuals
on those - Over the age of 50 years
- Willing to undergo a cognitive evaluation
(telephone or in person) - Siblings and offspring of affected individuals
- Some others very much want to participate use
judgment!
9Preliminary Pedigree
10The Preliminary Pedigree
- Is sent to the Coordinating Center at Columbia
and should include - Diagnosis
- Current age
- Age at onset
- Who will likely be sampled
- It is highly recommended to include the family
and individual number.
11Data Collection
12Study Visit/Data Collection
- Based on recommendations from the Coordinating
Center - Samples and study visits are collected from all
targeted individuals who are willing to
participate
13Minimal Dataset
14Minimal Dataset
- A minimal dataset must be completed for all
individuals from whom a biological sample has
been sent to NCRAD - Includes deceased individuals when an autopsy
specimen is being sent
15Minimal Dataset
- The minimal dataset is transferred each quarter
to Indiana University. The contact person is - Michael Daubs, Database Manager
- email mdaubs_at_iupui.edu
- tel 317-278-2608
16Sampled Pedigree
17The Sampled Pedigree
- Is sent to the Coordinating Center at Columbia
and should include - All individuals identified by their family and
individual number. - Who was sampled.
- Who had a minimal dataset collected.
- Who had neuropsychological testing
18Sampled Families
- A family cannot be considered completed or
sampled until the minimal dataset is
transferred to NCRAD for all biologically sampled
individuals - This is essential, since without the minimal
dataset, we can determine whether the family
meets the study criteria
19Pedigree Sample Reports
Fam ID Ind ID Sample at NCRAD? Data Set at NCRAD? Need Data? Comments
601 19 Yes Yes No
601 20 Yes Yes No
601 32 Yes No Yes Need data
601 33 Yes No Yes Need data
601 21 No Yes No
601 22 Yes Yes No
601 23 No Yes No
20Pedigree Sample Reports
Fam ID Ind ID Sample at NCRAD? Data Set at NCRAD? Need Data? Comments
565 9 No Yes No
565 7 Yes Yes No
565 10 No Yes No
565 26 Yes No Yes Have sample, not on pedigree, no data set on file.
21Pedigree Sample Reports
- NCRAD sends out this report after receiving a
copy of the sampled pedigree. -
- This report highlights missing data that is
required for a family to be considered sampled or
complete. -
- Important for sites to respond and submit missing
information
22Qualified Families Based on Submitted Data
- 205 families have a minimal dataset submitted to
NCRAD for at least one family member - Only 90 families consist of
- At least 2 siblings with a minimal dataset
supporting AD - At least one other biologically related family
member meeting the age requirements and with a
minimal dataset
23Qualified Families Based on Submitted Data
- In the majority of families who do not qualify,
the problems are - A minimal dataset has not been submitted for the
critical individuals - Missing variables in the minimal dataset preclude
the family from qualifying - There are a small number of families who will
never qualify. NCRAD and Columbia should be
informed when the sampled pedigree is submitted
24Samples to Researchers
- Researchers can request LOAD samples
- At this time, with only limited MDS data, no
requests have been processed - MTA out would be required
- Requests for samples should include
- IRB approval for proposed analyses
- Investigator CV
- Short description of proposed studies
25Minimal Dataset and Sampled Pedigree
- These are both critical elements that the site
must submit. - Without both of these elements, NCRAD and
Columbia can not determine if a family meets LOAD
criteria. - Without both of these elements, the family will
not be as useful to researchers!