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

Identify Appropriate Identify Appropriate FamiliesFamilies

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!

Preliminary PedigreePreliminary Pedigree

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.

Data CollectionData Collection

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

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: mdaubs@iupui.edu tel: 317-278-2608

Sampled PedigreeSampled Pedigree

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!