Frequently Asked Questions
for
Human Whole Genome STRP Linkage Scans

Genotyping |  Laboratory and Data Details |  Application Process |  Specific Investigator Questions

Genotyping

Will my data be kept confidential?
Yes. All data generated by CIDR will be kept strictly confidential. The data belongs solely to the submitting investigator. CIDR requests only an acknowledgment upon publication of any results.

How is the genotyping done?
CIDR utilizes automated fluorescent microsatellite analysis using a marker set composed primarily of trinucleotide and tetranucleotide repeats. This marker set consists of ~400 primer pairs with average spacing of 10 cM throughout the genome. There are no gaps in the map larger than 18 cM. CIDR currently multiplexes the products both pre- and post-amplification.

What is the facility's genotyping capacity?
CIDR is a high-throughput genotyping facility. Currently, CIDR is able to process approximately ~26,000 samples (11 million STRP genotypes) per year. A genotype is defined as one DNA sample x one microsatellite marker.

What are CIDR's performance goals?
CIDR strives for 95% completeness of all projects. This means that, excluding samples that fail > 25% of the time, the average missing data rate across all samples will be <5%. CIDR also strives for a <1% genotyping error rate as measured by project-specific blind duplicate samples provided by the investigator.

What quality control measures are in place at CIDR?
All genotyping will be done blind with respect to phenotype and family relationship. The key to break the code correlating CIDR's sample IDs with those of the investigator is available only to the Center's statistical genetics staff members. CIDR runs four CEPH controls, four blind duplicates provided by the investigator, and two blank PCR controls along with 86 experimental samples on each 96-well plate. The blind duplicate samples are assigned "dummy" CIDR IDs before being put into production. The error rate per genotype for each project is calculated from the blind duplicate samples.

Potentially problematic calls identified using internal QC measures are reviewed manually. All genotyping data is binned and is checked for consistency with Mendelian inheritance patterns where pedigree structure allows. Also, the pedigree structure file is checked against relationships inferred by genome scan data.

How much DNA is required?
CIDR requires 20 µg of DNA per sample. Prior to initiating the whole genome scan, all samples will be run with several test markers to ensure acceptable DNA quality and quantity.

Can I get help with study design and statistical data analysis?
Yes. CIDR has statistical geneticists on staff who are available to assist investigators. These services are beyond the normal services of CIDR and require a collaborative arrangement between the parties. This collaboration should be documented in the application.

Does CIDR do fine mapping of a region?
Yes. CIDR offers a Custom SNP Genotyping service for fine mapping projects.

Will CIDR do polymorphism typing for candidate genes or genotyping of only gene-rich regions?
Yes. CIDR offers a Custom SNP Genotyping service for candidate gene projects.

What happens to the DNA from my project at the conclusion of the study?
CIDR requests the amount of DNA that is, in general, necessary to complete a project. At the completion of a project there is generally very little or no DNA remaining. If a small amount is remaining at the end of a project, it is disposed of as biohazardous material.

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Laboratory and Data Details

In what format will CIDR provide the final data at the end of the project and what kind of assistance will I receive after project completion?
Upon project completion, CIDR will provide the investigator with compact disks containing the final data. A secured back-up copy of the data will be kept on-site. CIDR staff will be available to answer questions regarding completed genotypes after project completion.

How do I label my samples?
As soon as CIDR receives the sample/pedigree information, corresponding barcode labels for the samples will be generated and sent to the investigator.

Can I submit blood samples to CIDR?
No. CIDR accepts only DNA samples.

Will the DNA samples undergo any preliminary evaluations at CIDR?
Yes. Before a sample is put into genotyping production, it will be tested in three ways:

1. It will be tested for its ability to undergo successful amplification as determined by pre-screening with approximately 21 primer pairs. If a sample performs poorly, the investigator is given an opportunity to send a replacement sample. We recommend that replacement samples either be derived from an independent extraction or, if from the originally sent stock, have undergone a clean-up step.
2. It will be evaluated using X and Y chromosome-specific primers. The investigator will be given the opportunity to resolve any gender inconsistencies prior to production.
3. It will be evaluated for pedigree consistencies using information supplied by the investigator. Inconsistencies will be reported to the investigator.

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Application Process

For full details on the application process and related information, see Application Information.

How does an investigator gain access to CIDR?
All investigators requesting access to CIDR must submit a short application that describes the project and justifies the need for high throughput genotyping. All projects requesting access to CIDR are evaluated by the CIDR Access Committee (CAC), a committee of scientists with expertise in the analysis of genetic diseases/traits. The CAC is a chartered committee of twelve members that meets three times per year. Special reviewers are brought in as necessary.

Does an extramural investigator need prior approval from the supporting institute before submitting an application to CIDR? Yes. All projects require prior approval from the institute liaison before submitting an application to CIDR.

Is there a specific application form?
There is no specific form to complete. However, certain information is required from investigators requesting access to CIDR and a set of guidelines has been established. Investigators are asked to address a list of items in an application not to exceed ten pages, single-spaced.

When are applications due?
CIDR will accept applications three times during the year. Deadlines are March 1, July 1 and November 1. Applicants requesting access to CIDR prior to submitting their NIH grant applications are encouraged to submit these access applications at least one round (three to four months) before their NIH research grant applications are due.

What determines whether a project gains access to CIDR?  What are the specific evaluation criteria used by the CAC? 
In order to assess the likelihood of mapping a disease/trait, the CAC specifically focuses on several areas. The CAC will try to determine if the investigator and collaborators can: provide convincing evidence of a genetic contribution to the disease/trait; perform high quality and complete phenotyping of the study subjects; provide an appropriate study design for this specific mapping project; provide evidence of sufficient statistical power to detect linkage; and provide a plan to analyze and manage the data. Since the ultimate goal of a mapping project is to clone disease and/or susceptibility genes, the plans for follow up, if linkage is found, will also be important in the CAC's assessment.

Is the CAC like a study section?
For applicants who have already collected the majority of their samples, are ready to begin genotyping, and are not seeking new NIH funding, the role of the CAC is similar to a study section. Since the number of mapping projects granted access to CIDR may exceed the current capacity of the Center, projects granted access to CIDR will be prioritized by the Board of Governors. While the main criterion for granting access is the likelihood of successfully mapping the disease/trait, the final ranking of accepted projects include the significance of the disease for medical and/or biological implications and the plans for successful follow up if linkage is found.

What happens after the CAC reviews an application?
The results of the CAC review will be reported to the CIDR Board of Governors. The Board makes the final decision about which projects are accepted.

Do applicants receive feedback after the review?
All applicants receive a short summary highlighting the basis for the CAC's recommendation.   Unsuccessful applicants can amend their applications and resubmit for the next, or a subsequent, deadline.

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Specific Investigator Questions

All of these scenarios require a formal CIDR application. See Application Information for more details.

I am interested in mapping genes that might contribute to a complex disease I have been interested in for many years. I want to apply for NIH funding to identify and recruit more families, conduct interviews, collect diagnostic information, etc. I would like CIDR to do the genotyping. What will I need to do?
You need to prepare an application for CIDR access. If access to CIDR is granted, you will receive a letter of commitment stating that CIDR will perform the genotyping once you obtain the samples. This letter can be included with your NIH grant application or forwarded to the Initial Review Group (IRG) prior to its meeting.

I am a long time grantee of the NIH and over many years have collected enough family material to begin a linkage analysis in an attempt to map genes contributing to a complex trait. I had planned to perform the genotyping in my laboratory. Can CIDR perform the genotyping? If so, what will I need to do?
You can request that CIDR carry out the genotyping. You need to prepare an application for CIDR access.

I was a grantee of the NIH and used these funds to amass a large collection of DNA samples and cell lines that could be used for a linkage study to map a genetic disorder. My support came primarily from one of the twelve institutes supporting CIDR but I currently have no active support from the NIH. Will CIDR do the genotyping for free? Can CIDR personnel carry out the linkage analysis for free since I have no active support?
Under the current pricing structure, if one of the twelve supporting institutes funded the sample collection phase of the study, then the genotyping will be free. With respect to free data analysis, you will have to contact CIDR personnel to arrange a collaborative relationship to conduct the linkage analysis. If CIDR personnel agree to collaborate with you to carry out the linkage studies, there will be no charge for their services. If collaborative arrangements cannot be made with CIDR personnel, you will have to arrange a suitable collaboration on your own. In either case, you need to prepare an application for CIDR access.

I am an intramural scientist at the NIH. I have a long-standing interest in determining the etiology of a disease that is common in the population, and my colleagues and I have completed epidemiological studies targeted to dissecting genetic and environmental factors contributing to the disease. We have already completed the major work showing that there is a genetic component to the disorder and we want to design a research program to investigate the genetic components. Once we have collected samples, we want to attempt to map the gene(s) by genotyping across the entire human genome. How can I gain access to CIDR?
Your project will be reviewed by the CAC once you submit an application for CIDR access.

I am a research scientist whose genotyping project is funded by a for-profit institution. Can I get my genotyping done at CIDR?
Yes, provided your application is positively reviewed by the CAC and by the Board of Governors. The pricing schedule for genotyping depends on the project's source of support.

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Genotyping |  Laboratory and Data Details |  Application Process |  Specific Investigator Questions