NCRAD Update NCRAD Update
Tatiana Foroud, Ph.D.Tatiana Foroud, Ph.D.
Indiana UniversityIndiana University
Identify Appropriate Families
Send Columbia a Preliminary Pedigree
Obtain samples/complete study visits
Transfer Minimal Datatset to NCRAD
Send Columbia the Sampled Pedigree
Appropriate Families for Appropriate Families for StudyStudy
At least 2 living siblings with LOAD (onset > 60 years)
At least 1 other living related family member who :
Has AD (onset > 50 years)
Or
Is unaffected (> 60 years)
Who to collect?Who 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.
Which are the best Which are the best families?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.
Who to CollectWho 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 > 50 years
Query for any other affected cousins, half siblings, aunts, uncles??
II
IIII
IIIIII
Unaffected IndividualsUnaffected 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!
The 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.
Study Visit/Data CollectionStudy Visit/Data Collection
Based on recommendations from Based on recommendations from the Coordinating Centerthe Coordinating Center– Samples and study visits are collected Samples and study visits are collected
from all targeted individuals who are from all targeted individuals who are willing to participatewilling to participate
Minimal DatasetMinimal 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
Minimal DatasetMinimal Dataset
The minimal dataset is transferred each quarter to Indiana University. The contact person is: Michael Daubs, Database Manager email: [email protected] tel: 317-278-2608
The 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
Sampled FamiliesSampled 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
Pedigree Sample ReportsPedigree 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
Pedigree Sample ReportsPedigree Sample Reports
Fam ID Ind IDSample 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.
Pedigree Sample ReportsPedigree 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
Qualified Families Based Qualified Families Based on Submitted Dataon 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
Qualified Families Based Qualified Families Based on Submitted Dataon 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
Samples to ResearchersSamples 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
Minimal Dataset and Minimal Dataset and Sampled PedigreeSampled 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!