for the EU GSA consortium

concerning the global screening array

 

 

 

Search FAQs for information on:

 

Ordering and payment

Legal

Pricing of the array

DNA samples

Genotyping data and deliverable

Additional services

Genotyping schedule

Custom content

Blood and saliva isolation

Contact and information on HuGe-F

 

 

ORDERING AND PAYMENT

 

1. Can I increase the number of samples in my existing order?

If you have already joined the consortium by placing an order and you are interested in ordering more samples, you can place an extra order. You will receive a new quotation and contract based on the sample price of your first order.

 

2. Can I place an extra order, on top of my initial order?

Yes. You can place an extra order. You will receive a new quotation and contract based on the sample price of your first order.

 

3. Until when can I place (extra) orders in the GSA consortium?

You can place (re-)orders for genotyping at HuGe-F at Erasmus MC until May 15th 2019.

 

4. Can I order the arrays through HuGe-F and do the genotyping myself?

No. We require, under the terms and conditions with Illumina and the EU GSA consortium, the samples to be genotyped at HuGe-F Erasmus MC.

 

5. When do I have to pay for my order?

For the genotyping service at HuGe-F Erasmus MC, the first payment needs to be done, one month before running your samples. The receipt of payments of the ordered arrays (which represent the order of the arrays and 80% of the running costs) is a prerequisite for the start of the process of genotyping.

The final 20% of the running costs will be invoiced to you before delivery of the genotyping data. Upon reception of this final payment we will send you the deliverables.

 

6. I did not order before July 31st 2016. Can I still join the consortium and order the Global Screening Array?

Yes. You can still join the consortium and let your samples be genotyped at HuGe-F. The consortium sample price for normal genotyping service at HuGe-F is <€35 (VAT not included), depending on the number of samples. Please contact us for exact prices.

 

 

LEGAL

 

1. Can we change the contract from Dutch Law to law of our home country?

No. Dutch law applies to this contract and the products and services delivered by us at Erasmus MC, Rotterdam, The Netherlands.

 

 2. Do you need the contract signed by a legal representative?

Yes, but you have to decide who that legal representative is. There is no general answer to this question. It is up to your own institute to decide who is legally responsible for signing the contract. Sometimes these decisions also depend on the amount of money involved.

 

PRICING OF THE ARRAY

 

1. What is the price for genotyping with the global screening array at HuGe-F?

The consortium sample price for normal genotyping service at HuGe-F is <€35 (VAT not included), depending on the number of samples. Please contact us for exact prices.

 

2. I did not order before July 31st 2016. Can I still join the consortium and order the Global Screening Array?

Yes. You can still join the consortium and let your samples be genotyped at HuGe-F. The consortium sample price for normal genotyping service at HuGe-F is <€35 (VAT not included), depending on the number of samples. Please contact us for exact prices.

 

3. Do I have to pay VAT?

Whether you have to pay VAT, and the amount of VAT you have to pay, depends on the laws that are applicable in your country. The actual text in the contract reads this: “The prices are quoted in EURO’s excluding VAT. VAT may be added in the invoice if applicable. It is well understood that to these services the VAT is shifted based on article 44 jo. Article 196 of the EU VAT directive (2006/112/EG).”

Within the Netherlands, 21% VAT will be added in the invoice. VAT can be shifted between countries.

 

4. Will the quotation be in dollars?

No. The quotation/contract you receive from HuGe-F, will be in EURO’s.

 

5. What is included in the sample price?

The sample price includes the costs for consumables (e.g. the array), the costs for performing the genotyping service at the HuGe-F at Erasmus MC and delivery of the data (of the total amount of samples) to you.  

 

DNA SAMPLES

 

1. Is there a protocol for shipment of the DNA samples?

Yes, there is a strict protocol and we request you to contact our lab BEFORE sending any samples.  The protocol will be sent to you when you sign a contract. You can also download the DNA shipment protocol from the HuGe-F website <link> here.

If you don’t follow the DNA shipment protocol and we need to perform extra work to prepare your samples, we will invoice you accordingly. Extra costs will be communicated and agreed on, before any extra work is done.

Not following the protocol will result in a delay in delivering the genotyping data.

 

2. To what address do we ship the DNA samples?

You can only send DNA samples to our lab IF we have approved of you doing so following the DNA shipment protocol. Our address is:

Human Genotyping Facility (HuGe-F)

Genetic Laboratory

Department of Internal Medicine

Erasmus MC Rotterdam

Westzeedijk 353

3015 AA Rotterdam

The Netherlands

 

 3. What quantity of DNA is required?

200 ng DNA is required for Illumina GSA Beadchip. Please send only 200 ng of DNA in 4 to 10 ul. This amount of DNA is not sufficient for a possible redo. When more than the required amount of DNA has been shipped to us, it can be sent back at your cost.

We will keep any surplus DNA of your study in our facility during your project. Once genotyping data has been delivered we will remove this surplus.

 

 4. Will DNA samples be sent back after genotyping?

Please don’t send us more DNA than we have indicated in the protocol! When we have received more than the required amount of DNA, it can be sent back to you upon request and at your cost.

 

5. Can I use heat seals on the plates with DNA?

No. Please do not use heat seals.  There is a strict protocol for sending the DNA samples, please follow this protocol.

 

6. There are empty wells in my plates. Is this a problem?

Yes. You should NOT include ‘blancs’ in the plate. Because of the automation systems and the lab procedures, empty wells will not be filled manually. These wells will thus be genotyped on the array, which results in extra costs (and no extra data). If you leave empty wells in the plates you will receive a contract for these blancs, and you will be invoiced. You will pay the sample price per blanc.

 

7. What plates do I need to use when sending in the DNA samples?

For shipping of samples to HuGe-F we require Abgene Storage Plates, 96-well, 0.8 mL (Thermofischer, REF:AB0765). No other plates are accepted. We refer to the DNA shipment protocol for more details regarding shipment.

 

8. Do I need to perform a DNA integrity check?

Yes, but not necessarily on all samples. You should perform a DNA integrity check by placing a random selection of 5 to 10% of the samples on agarose gel. We would like to receive a picture of this gel. Based on these pictures we determine how to proceed. Do not send in any material before we have approved of your gel pictures.

Please follow the DNA shipment protocol before sending in your DNA. It will be sent to you when you sign a contract. You can also download the DNA shipment protocol from the HuGe-F website <link> here.

 

9. Our order /contract consists of samples from multiple centers. Can each center send in their DNA separately?

No. We require samples to be shipped to us through one party per contract.

 

10. Do I need to code the DNA/blood/ saliva samples?

Yes. All samples should be uniquely coded. Codes should not include any personal information.

 

11. Do I need to label the plates I send in?

Yes, each plate you send to us, should be labelled appropriately with your GSA project reference number (which can be found on your contract), plate number and name of the research center.

 

 

GENOTYPING DATA AND DELIVERABLES

 

1. Which variants or SNP’s are on the array?

In total more than 700,000 SNP’s are on the array. representing different categories of DNA variants. The exact identity of the SNP’s can be found in the so-called SNP list. This list is available and can be downloaded from the HuGe-F website. <link>

 

2. When do I receive my genotyping data?

Upon signing the contract, you will receive an estimated period in which your samples will be run. Upon reception of your total payment we will send you the deliverables.

Given the large volume of samples we are processing for many different customers, the genotyping service will take about 1 to 2 months after reception of your samples at HuGe-F. Timely delivery of the data can only be guaranteed when we receive the DNA samples at the agreed time and according to the guidelines in the DNA shipment protocol.

 

3. What deliverables can I expect?

You will be provided with a Beadstudio project file with sample genotype per SNP and accompanying intensity iDAT files, report files in plain text format containing a summary table with information for all individuals and genotypes per sample or plink files. A minor QC report will be provided detailing QC steps and possibly recommendations for further QC. All data will be provided in a zip folder.  The size of the file depends on the project size. For a project of moderate size (~1,000 samples) this is 18 GB.

 

4. How will the genotype data be supplied?

Genotype data will be supplied by filesender and will be placed in an encrypted zip file. The decryption code will be send separately.

 

5. What is the delivery time of my genotyping data by HuGe-F?

It depends. We have two types of projects. One with and one without a guaranteed Turn Around Time (TAT). Under normal circumstances (projects without guaranteed TAT) delivery of genotyping data will take place within 1-2 months after delivery of the DNA samples to Hu-Ge-F. We also offer a guaranteed 2-week and 4-week TAT, but at higher costs. If you are interested in this latter option, please contact us.

Timely delivery of the data can only be guaranteed when we receive the DNA samples at the agreed time and according to the guidelines in the DNA shipment protocol. Please also note that we require a strict payment scheme for your samples to be processed and data to be delivered.  Data will be delivered when all invoices have been paid.

 

6. Can we receive our data sooner than the normal 1-2 months delivery time?

We also offer guaranteed 2-week and 4-week TAT, but at higher costs. If you are interested in this latter option, please contact us.

 

7. Wat is the call rate for genotyping?

If DNA-quality is OK (see the DNA shipment protocol), in general >99% of the samples has a good SNP call rate. The process of running the samples has almost completely been automated.

 

 

ADDITIONAL SERVICES

 

1. Are there additional services?

The HuGe-F at Erasmus MC offers a number of additional services to provide a comprehensive level of support for your genotyping project. Please see our website for more information. Services that are available on request prior to genotyping are DNA extraction/purification, sample DNA concentration/normalization, and biobanking.

After the genotyping of your samples has taken place, we also offer extensive data storage, extensive quality control (including zCall), as well as imputations to various reference panels, including HapMap, 1KG, and HRC.

All additional services are available at extra costs.

 

2. What are the costs for DNA extraction/purification?

The HuGe-F can provide DNA purification services. DNA purification service includes necessary dilution and preparation for direct downstream use in the genotyping process. Prices for these services depend on the number of samples. For an overview of acceptable biomaterials as DNA sources and exact prices, please inquire.

If you don’t request further services at the HuGe-F, you will receive your normalized DNA in a 96-deep well plate, as well as the barcoded tubes with stock DNA that has not been normalized. Costs for sending the DNA is not included in the project price, and will be discussed and quoted separately.

 

3. What is included in the DNA purification service?

DNA purification service includes necessary dilution and preparation for direct downstream use in the genotyping process. After isolation you will receive report files containing summary table with information for all individuals (sample purity, concentration and yield).

If you don’t request further services at the HuGe-F, you will receive your normalized DNA in a 96-deep well plate, as well as the tube DNA that has not been normalized. Costs for sending the DNA is not included in the project price, and will be discussed and quoted separately.

 

4. Can DNA be stored at HuGe-F, and what are the costs?

Yes. HuGe-F offers DNA-sample storage following DNA-isolation at our lab. DNA is stored in a monitored -80oC freezer. The price for this service is a single registration fee of €1.50 per sample and additionally €0.05 per sample per year.

 

5. What are the costs for DNA normalization?

HuGe-F offers normalization to 50 ng/ul in a 96-deep well plate and plating (in 96 and/or 384 well plates) of DNA from tubes. The price for this service is € 1.00 per sample.

 

6. Can genotyping data be stored at HuGe-F, and what are the costs?

Yes. Data generated in a project for HuGe-F will always be stored including raw intensity files in uncompressed format for 1 year after obtaining genotypes for your samples, and at no extra costs. After 1 year your data will be deleted. Storage duration longer than 1 year can be offered upon request. The price for this service is € 4.50 per sample. We store our data at an ISO/NEN certified external server, in a monitored datacenter in Rotterdam, the Netherlands.

 

7. How is data stored when samples are processed at HuGe-F?

We store our data at an ISO/NEN certified external server (ISO/IEC 27001:2013; NEN 7510:2011). Data storage at Erasmus MC is password protected; data is stored behind a firewall. Additionally the data is stored in two locations (in- and outside Erasmus MC) to avoid data loss.

 

8. Will quality control be performed on the genotyping data?

Yes. By default we provide a standard short QC report informing sample call rates (i.e., the proportion of variants successfully called per sample). These call rates are determined using a customized cluster file generated at HuGe-F Erasmus MC, in collaboration with Illumina.

 

9. Should I perform an extended more comprehensive quality control?

That depends on your plans, expertise and requirements. A comprehensive QC is highly recommended if you are inexperienced in genetics or GWAS and need rare variant calling, or need genotype imputation to large reference panels, such as HRC, and will be running genetic association testing by GWAS with the newly generated genotyped data.

 

10. Does HuGe-F offer extended quality control, and what is included?

Yes. This extended QC includes (but is not limited to) sample call rate pruning, marker call rate pruning,  Hardy-Weinberg Equilibrium determination, excess heterozygosity check, gender check, ethnic outlier check and cryptic family relatedness determination.

Because of the considerable number of rare variants on the GSA array, zCall is included in the extended QC. Deliverables of this extended QC include an extensive QC report with full details of the steps performed.

 

11. Is rare variant calling necessary?

Given the considerable number of rare variants on the array (more than 50,000 variants) an additional calling step with zCall1 is recommended to improve the calling of such rare variants.

1 B. Neale, Lab BROAD Institute

 

12. Does HuGe-F offer rare variant calling?

Yes. For the GSA, zCALL1 is performed after the comprehensive QC.  After zCall, an additional QC is performed on the called rare variants.

1 B. Neale, Lab BROAD Institute

 

13. What are the costs for the extended quality control?

HuGe-F at Erasmus MC offers an extended QC. Prices depend on the number of samples. Please contact us for further information.

 

14. Can I perform imputations myself?

Yes. But only if you are very experienced in this field. Imputation of datasets is a very complicated and computationally-demanding process. Yet, imputations can be performed free of charge using web-based services offered by the Haplotype Reference Consortium (HRC) at the University of Michigan (Abecassis Lab) and the Wellcome Trust Sanger Institute (Marchini Lab). We recommend customers who are less experienced and/or have no access to collaborators who can work with these resources to contact us (see 47-49.).

 

15. Does HuGe-F offer imputation services?

Yes.  We offer imputation service. Prices depend on the number of samples. Please contact us for further details.

 

16. Does HuGe-F offer imputation services and what is included in the imputation services offered by HuGe-F?

Yes. HuGe-F offers pre-processing (formatting) your data for the Michigan Imputation Server and generating a post-imputation QC report.  In this report, we determine the mean imputation quality of your samples analyzed per chromosome. Imputations can be performed to the following reference sets: HapMap (~2.5 M variants), 1000 Genomes (Phase 1 or 3) (~12 M variants), CAAPA and HRC (~30 M variants). We recommend HRC as it is the biggest reference panel and provides the best quality imputations. Please contact us for further information.

 

17. Are there data security considerations we have to take into account regarding imputation?

For HRC imputations, the Michigan Imputation Server provides a number of safeguards for data protection, namely:

• Interaction with server secured with HTTPS

• Data upload via sftp

• Input data is deleted when run is finished

• Only number of samples and markers analyzed stored (no cohort name or information stored)

• Results encrypted with strong one-time password

• Imputation results deleted after 7 days

 

18. What are the costs for the imputation services?

HuGe-F at Erasmus MC offers imputation services. Prices depend on the number of samples. Please contact us for further information.

 

19. Does HuGe-F offer data depositing in the database of Genotypes and Phenotypes (dbGaP)?

No. This service is not offered by HuGe-F.

 

 

GENOTYPING SCHEDULE

 

1. When will my samples be genotyped?

For all GSA customers at HuGe-F a genotyping schedule is established taking into account the preferences of the customers and the possibilities of our lab. The date of signing your contract is an important criterion for placement in the schedule. Timing of genotyping will be discussed with individual customers, and will be communicated individually.

 

2. Can I send in DNA samples in advance?

No. Only once you have signed the contract AND contacted the HuGe=F lab you can send in your samples We indicate this possibility in e-mail correspondence regarding the genotyping schedule. If you want further information, please contact us.

 

3. When will the genotyping data be delivered?

The delivery date of genotyping data will depend on the size of the project, delivery date of samples to be genotyped to HuGe-F, and the current queue of projects at the HuGe-F genotyping facility. A delivery date will be agreed on at the start of the project. Please note a project will be set in the queue of projects only after a signed contract has been received by the HuGe-F.

For projects without guaranteed TAT, the delivery of genotyping data takes place within 1-2 months after delivery of the DNA samples to HuGe-F. Timely delivery of the data can only be guaranteed when we receive the DNA samples at the agreed time and according to the guidelines in the DNA shipment protocol. Also, we will only send the deliverables upon receipt of payment of the invoices.

 

CUSTOM CONTENT

 

1. The array has a possibility of 50K custom SNPs. How is this custom content going to be determined?

If no custom content is specified, a standard content set of GWAS fine-mapping variants is added to the GSA. But the custom content can also be specified. This is done in two ways, either through a “shared” custom content or through a “private” custom content. Shared custom content was possible at the start of the consortium, and is now closed.

 

2. What is meant by shared custom content?

This is a specific custom content added to the GSA array content. Before the deadline of July 31st, it was possible to compose a so-called “shared custom content”. Only nine GSA customers have chosen for this custom content for their samples and contributed to the composition of the specific SNP content of this “shared custom content”. That 50K custom content was specified according to the specific wishes of the nine centers that joined the shared custom content.  This shared custom content, however, is now fixed and it is not possible to change or add SNPs anymore.

 

3. What is meant by “private” custom content, and what are the criteria for ordering this?

If you choose private custom content for the GSA arrays for your sample set, you can create your own custom SNP list (anywhere between 10k-50k SNPs) and discuss the details with Illumina. Your list will undergo scrutiny for suitability. No other groups will get access to the SNP list of this custom array. The minimum number of samples for production of a private custom content GSA array is 10,000 which is the minimum number of samples for which you have to buy GSA arrays. Please contact us for further details.

 

 4. What are the costs for “private” custom content?

The private custom content GSA array will cost extra based on the exact number of SNPs you want in the private content and the number of samples you order the GSA array for. Please contact us for further information.

 

5. When are GSA arrays with custom content available?

Producing a customized GSA array by Illumina will take minimally 6 months, and so customized GSA arrays will be available later than normal GSA arrays. We expect the shared custom content arrays to be ready in the second quarter of 2017.

 

BLOOD AND SALIVA SAMPLES FOR DNA ISOLATION

 

1. How do I send in blood samples?

For DNA isolation services you will need a separate contract. Blood samples should be securely wrapped and shipped on ice by overnight courier. Do not ship samples on a Thursday, Friday or Saturday. Before sending the samples please first contact our HuGe-F lab. Report exact time, date, shipment number etc. before sending the samples, and we will notify you upon receiving the samples. And please do not forget to email an excel file with the sample IDs and gender of samples.

Please also see the DNA processing contract for sample submission criteria.

 

2. How do I send in saliva samples?

Saliva samples should be sent at room temperature. Do not ship samples on a Thursday, Friday or Saturday. Before sending the samples please first contact our lab. Report exact time, date, shipment number etc. before sending the samples, and we will notify you upon receiving the samples. And please do not forget to email an excel file with the sample IDs and gender of samples.

Please also see the DNA processing contract for sample submission criteria.

 

3. Can I send in samples during the weekend?

No. Please, do not ship samples on a Thursday, Friday or Saturday.

 

4. Is there a protocol for taking and delivering blood for DNA isolation?

Yes. You should take the following criteria into account when taking and delivering blood:

• Use 5 ml EDTA blood / Buffy coat from 5 ml blood in plastic tubes.

• Invert the tubes a couple of times after taking blood.

• Freeze the samples within 4 hours after taking blood.

• note study name and study number on tube

 

CONTACT AND INFORMATION ON HUGE-F

 

1. Who do I contact for more information?

For information please contact the GSA project manager dr. Gaby van Dijk

 

2. I want to know the names of other cohorts in the consortium. Is this possible?

No, not yet. The names of participating cohorts and investigators and research groups are confidential. We are planning, however, to make names available to those consortium members who agree to this. This will be organized in the near future.

 

3. Is HuGe-F a certified lab?

Yes. HuGe-F is an Illumina certified lab and has recently received a Propel certificate. Furthermore our ICT/data handling operates under the following certificates: ISO/IEC 27001:2013 and NEN 7510:2011.

 

 

4. How is the stored DNA secured?

Stored blood and DNA is secured by an alarm system which is connected to our freezers. If the temperature of the -20C freezers rises to -10 degrees, lab technicians will be alerted who will transfer samples to back-up freezers if necessary. To prevent unauthorized access to the stored batches of DNA, we have pin code secured locks on the doors to our laboratories. Additionally, the freezers are locked. To maintain a robust data trail from DNA sample to data we will use a LIMS system.

 

5. What measures are there to maintain a robust data trail?

To maintain a robust data trail from DNA sample to data we use a LIMS Clarity system.