Co-ordinator: Jan Traeger-Synodinos

 

Objective:

A comprehensive collection of SNPs which are not associated with an obvious change in phenotype. Information will include phenotypic characteristics in carriers and /or patients as available, relative frequency in relevant population group, simple PCR assay (eg RE-PCR) if available, etc.

 

Background:

There is no comprehensive collection of globin gene SNPs which are not associated with an obvious change in phenotype. Present sources of information include various publications or databases such as the SNPper Sequence Viewer in the CHIP Bioinformatics Tool (http://snpper.chip.org/), but they are incomplete.

 

Current state of the Art:

Some SNPs are reported, for example in the main database for Human Haemoglobin Variants and Thalassaemias (HbVar database; http://globin.bx.psu.edu/hbvar), but whether they have any consequences on phenotype is not always clarified. With the application of technologies such as DHPLC and sequencing, SNPs are often detected in DNA samples from patients and /or potential carriers of thalassaemia, but information to support evaluation on their potential phenotypic consequences is sparse.

 

Expected benefits of project:

A comprehensive collection of SNPs is expected to be beneficial for a) evaluation of observed SNPs in the context of clinical diagnostics; b) possibly providing information on new, so far unidentified mechanisms controlling globin gene expression and/or globin polypeptide synthesis; c) as tools for linkage analysis in procedures such as non-invasive prenatal dagnosis.  

 

Description and format of data to be collected by participants and emailed to project leader:

The variant base and position of each SNP should be reported within the relevant globin gene according to the Guidelines for Human Gene Nomenclature (http://www.hgvs.org/mutnomen/) from the Human Genome Variation Society (HGVS). This should be accompanied by the relative frequency in relevant population group and relevant haematological and clinical data. The  incorporation of the globin SNP databases within HbVar should be discussed.

An update on the SNP project:

 I have had response for participation from

Marina kleanthous + team, George Patrinos + Team, John Old, Piero Giordnao and Kees Harteveld, Joseph and Alex Felice, Nazli Basak.

So far I have received lists of SNPs from Marina kleanthous + team, George Patrinos + Team.

It would be gr8 if I can have lists from all the other centres that have shown interest to collaborate by mid October. 

I would prefer that everyone formats their SNP lists to be in-line with the way George has suggested we format them (see the email he sent to us all on Sept 10th with his example files), but if this is not possible, just send the lists as you have them and we can use this "forum" to discuss how best to make them in to a format that is both scientifically "correct" and useable (I fear the format from George may be beyond the understanding of many of us!!).

I await a response (through portal) from anyone who has comments or interest in this project.

Jan Traeger-Synodinos DPhil (Oxon)
Assistant Professor of Genetics,
Laboratory of Medical Genetics,
University of Athens
St. Sophia's Children's Hospital
Athens 11527,
Greece
Tel: +30 210 746 7461
Fax: +30 210 779 5553
email: jtraeger@med.uoa.gr

We are interested in this project.

 

 

Dr. Ferda Ozkinay, Dr Hüseyin Onay 

Medical Genetics Department

Ege University, Bornova/İzmir Turkey

Fax: + 90 232 3904917

e-mail: f.ferda.ozkinay@ege.edu.tr

 

Dear All,

As co-ordinator of the Ithanet Co-ordination Project "Database for single nucleotide polymorphisms (SNPs) in globin genes" I would like to make a last call for all partners who have not sent in any data sets but who wish to participate. It would be ideal if everyone can repsond (even if it is with just a promise of a data set) by the end of this week so I can see what has been sent and then we can initiate a discussion on the most useful format (or formats if we want >1 database) for the SNP's, accoroding to who will be end users etc

So far I have had data sets from: Marina Kleanthous & Xenia Feleki (CING), John Old (ORH), George Patrinos (AG),

I have expression of interest but no data sets from:

Joseph and Alex (UoM), Roberto Gambari (UNIFE), Piero Giordano & Kees Harteveld (LUMC), Nazli Basak (BU), Dr. Ferda Ozkinay, Dr Hüseyin Onay, Medical Genetics Department, Ege University, Bornova/İzmir Turkey (which partner are you?), Ali Taher & Lama Bazzi (CCC).

I look forward to hearing from all those who have shown interest but have not sent in data yet - even if it is just which gene(s) and/or gene clusters and approximately when you might have them ready....

Best wishes,

Jan Traeger-Synodinos, Manolis Kanavakis (NKUA)

So far THE PROJECT LEADERS NKUA , P09 ) have received data sets from: Marina Kleanthous & Xenia Feleki (P01 CING), John Old (P05 ORH), George Patrinos (P08 AG), Joseph and Alex (P07 UoM), Piero Giordano & Kees Harteveld (P18 LUMC),

I have expression of interest but no data sets from:

Roberto Gambari (P11 UNIFE), Nazli Basak (P21 BU), Dr. Ferda Ozkinay, Dr Hüseyin Onay, ( P23 EUH), Ali Taher & Lama Bazzi (P15 CCC), Panagoula Kollia (which partner ARE YOU ?)

This project is still on-going so if anyone else has any data to submit please notify the project leaders (Jan Traeger-Synodinos and Manolis Kanavakis).

Best wishes,

Jan Traeger-Synodinos, Manolis Kanavakis (P09 NKUA)

 

Urgent Topic for Discussion : Format of globin gene cluster SNP databases

 

So far I have 6 SNP sets for the globin gene clusters (including our set at NKUA), and they are ALL DIFFERENT!!

 

I will outline the fields that each data set includes and then we can begin our discussion:

 

The P09 NKUA (my ) data set includes:

Only beta globin gene. Traditional nucleotide number of base substitution (and change), HGVS number (which I may have got wrong!), Method of detection, approximate frequency in he population.

 

Marina Kleanthous & Xenia Feleki (P01 CING):

Only beta globin gene. Traditional nucleotide number of base substitution (and change), HGVS number, Method of detection.

 

George Patrinos (P08 AG):

All beta globin cluster with ? SNPs copied from dbSNP??? And each SNP with an “rs” number. Maybe this is most “correct” but, for me at least, I cannot fathom how to relate the rs number to the globin gene regions themselves…….George please can you enlighten us in the simplest of terms perhaps?????

 

John Old (P05 ORH), data set:

Alpha and beta globin genes consisting of 2 extensive lists of SNPs found in individual samples eg DNA id, ethnic group, traditional nucleotide number of base substitution (and change), genotype of sample and beta gene mutation (if present), [in cis or trans to SNP ????]. 

 

Piero Giordano & Kees Harteveld (P18 LUMC):

All beta globin gene cluster. Despite the Dutch column headings I think that the data set includes gene region name (although some explanation is needed eg what is “preGframe” or “F2” or promAgextra” !!!!??), fragment co-ordinates according to NCBI, nucleotide substitution and exact SNP position (positie) according to NCBI.

 

Joseph and Alex (P07 UoM) data set:

Beta globin gene region plus XmnI site. I really had requested that the data be submitted in the form of a table listing the SNP, position, frequency in population etc …..so this data set will have to be converted (but wait for the consensus on what it should include etc)

 

In order to begin the discussion I will  ask and answer some  questions:

Q a) what is the aim of this database ?

Response to Qa) I THINK THE AIM SHOULD BE AN EASILY ACCESSIBLE REFERENCE TO i) IDENTIFY WHETHER A BASE CHANGE IN A SAMPLE IS POLYMORPHIC OR PATHOLOGICAL AND ii) LOCATE SNP’S THAT MAY BE USEFUL FOR LINKAGE ANALYSIS

 

Q b) What is the nucleotide numbering system that we should use to identify each SNPs to  preclude ambivalence!?

Response to Qb) CLEAR ID OF SNP USING BOTH NCBI CLUSTER NUMBERING AND “rs” NUMBER OF AVAILABLE.

 

c) What other fields are relevant ?

Response to Qc) ETHNIC GROUP AND RELEVANT FREQUENCY? [THE METHOD FIELD IS PROBABLY IRRELEVANT IN THE END…..].

 

SHALL I CIRCULATE THE DATA SETS THAT EVERYONE SENT ME SO THAT EVERYONE CAN ALL SEE WHAT I AM TALKING ABOUT? WHOEVER IS INTERESTED THEN LET ME KNOW....

 

And let the discussion begin……

 

Regards,

Jan

NKUA

Hallo everyone

I agree with Jan on Q a).

Response to Qb): the "rs" number is good and easily accessible on dbSNP database of NCBI but, as Jan mentioned earlier is that it is difficult to relate it with the SNPs that we use that have the traditional numbering or the HGVS nomenclature...maybe someone has suggestions to that? IF we use the HGVS nomencalture we can  locate it right away on the gene.

Moreover, I have noticed that some SNPs that we use (having the traditional numbering or HGVS nomenclature) do not necessarily have an "rs" number...So what do we do in that case?

Response to Qc) I believe that ethnic group and relevant frequency of each group are absolutely necessary since the frequency changes among populations.

 Jan, can i have the data sets that everyone sent? Thanks

 

Regards

 

Thessalia & Marina (P01)

Dear All,

I have only had a response from Thessalia on the globin gene SNP database project. I intend to send out an email to everyone that has so far sent me data for this project with attachments of the data that has been sent (probably 2 emails to support all attachments).

Please look at them and send in comments - or at least have them ready for next week so we can discuss them "live" during my allocated presentation time.

Jan NKUA P09

 

Dear All,

DEAR ALL,

JUST TO NOTE THAT I HAVE HAD NO RESPONSE FROM ANYONE ON MY DATABASE FOR SNPS IN THE BETA GLOBIN GENE?!

JAN 

Dear Mrs. Synodinos,


I am sending you by e-mail a slightly modified file considering your SNPs database. I have added the dbSNP annotation for some of polymorphisms mentioned and the U01317 base numbers as well.

I am also sending you a copy of the master (385kb) sequence with the SNPs annotated in it.

Last but not least, I am at your disposal in case you need any help incorporating Mr. Harteveld's and Giordano's SNPs in the Master sequence and the excel file.

Thank you in advance for your time.


Sincerely,

Konstantinos Varvagiannis
Laiko GH - Partner 13

Dear Contributor to the project "Database for single polymorphisms (SNPs) in globin genes"

Following the e-mail message addressed to the coordinators, whichI received from Marina:

 "Dear Ithanet projects Coordinators,I would like to ask you to organize at least one videoconference for each project in order to discuss with the other contributors the results and the possibility of preparing a publication. You can find the list of the coordination projects are on the Ithanet portal under the forums section. Please contact the contributors of each project in order to arrange the most suitable date. Best wishes, Marina "

 Therefore I would like to invite you for a video conference on either :

A. Monday 29 September at 1pm Greek time (12noon central European time) 0r

B. Wednesday 1 October at 1pm Greek time (12noon central European time).

to discuss how we can proceed on this subject. 

Please tell me your preference.

Best wishes,

Jan (University of Athens NKUA partner 9)