Help! Received Copy Of Genetic Test Results

[elle's mom]

OK, here are the results of my four kids genetic testing:

Serology

A B Cw DR DQ DQA DP8

5 (DD#1&DS)

6 (DD#1&DS)

2 (DD#2&DD#4)

5 (DD#2&DD#4)

These were listed under the DQ column but I could not get it to post like that.

Molecular

A* B* C* DRB1* DRB3* DRB4* DRB5* DQB1* DQA1* DPB1*

0501 0101 (DD#1&DS)

06XX 0102 (DD#1&DS)

0201 0101 (DD#2&DD#4)

0501 0501 (DD#2&DD#4)

Again, these were listed under the DQB1* & DQA1* columns.

Comments

(this is on all 4 reports)

The presence of HLA-DQA1*0501 and DQB1*0201 may be associated with an increased incidence of celiac disease. (Meaning DQ2-correct?) Gluten-derived peptides are presented by HLA-DQA1*0501-DQB1*0201 heterodimers and induce T cell mediated immune response to the small intesting mucosa. Studies of the celiac patient population have shown that 95% of these patients carry the DQA1*0501-DQB1*0201 heterodimer in linkage disequilibrium with a HLA-DRB1-03XX (DQ8?? this is me, not on the report) allele; celiac patients who are not HLA-DR3XX+ often are DR5/DR7+ (DQA1*0501-DR5+ and DQB1*0201-DR7+) in linkage disequilibrium. (don't get this part at all!?)

(this is on DD#1&DS reports only)

The HLA-DQB1*06 type is either HLA-DQB1*0604 or *0634 or *0636 or *0638 or *0639.

This patient is NEGATIVE for both HLA-DQA1*0501 and DQB1*0201.

High resolution HLA typing is complete.

(this is on DD#2&DD#4 reports only)

This patient is POSITIVE for both HLA-DQA1*0501 and DQB1*0201.

High resolution HLA typing is complete.

First of all, I may need to change my signature, which I put on after speaking with the genetic counselor on the phone because she told me DD#2&4 were positive for both DQ2&8 and to me this looks like they were positive for DQ2&5!?

If anyone can explain the bolded items, those are what I do not understand.

The reason we had genetic testing done was to determine which children had genes similar to those of our diagnosed celiac daughter. In regards to that and in light of these results, being that the two children negative for DQ2 are positive for DQ 5, as is our celiac daughter, is there any association (that you all are aware of) with the DQ 5/6 combination for either celiac or gluten senstitivity? I apologize for the length and complexity of this, but I feel I can get more accurate information here than from the genetic counselor who gave me the wrong information over the phone!!

[maile]

The reason we had genetic testing done was to determine which children had genes similar to those of our diagnosed celiac daughter. In regards to that and in light of these results, being that the two children negative for DQ2 are positive for DQ 5, as is our celiac daughter, is there any association (that you all are aware of) with the DQ 5/6 combination for either celiac or gluten senstitivity? I apologize for the length and complexity of this, but I feel I can get more accurate information here than from the genetic counselor who gave me the wrong information over the phone!!

Hi there, unfortunately I'm not sure about reading that test (hopefully one of the experts will chime in on that) but I do know about the DQ5/6 question. I'm double DQ5 and this is associated with gluten intolerance as well as with neurological manifestations of gluten intolerance.

[nora-n]

Linkage disequilibrium just means that some alpha and beta chains turn up together way much more often than not. In English: 0501 likes to hang around 0201 (which make up DQ2) etc.

On DQ5 and 6: Dr. Hadjivassiliou has researched gluten ataxia, and written several papers and done gene studies. He found that about 20% of his gluten ataxia patients had DQ1.

(DQ1 are DQ5 and DQ6)

The charts most easy to read for what the alpha and beta chains are, are at

Open Original Shared Link

but to get the DR part you need to look at the DR charts

Open Original Shared Link

Now the thing that might confuse you is the weird wording on the trans DQ2, which they call DR5/DR7 -DQ2. That just simply means the DQ2 molecule is made up from genes from two alleles. Usually the celiac genes are made up from one gene like the normal DQ2 which has 0501 in teh aplha chain and 0201 on the beta chain and DR3. Now trans DQ2 is made up of the non-DR3 DQ2,2 0202 beta chain plus 0505 or 0501 in the alpha chain from DQ7 on the other gene. (Now Enterolab for example does not test for alpha chains and does not report trans DQ2,5 when pepole have DQ2,2 and DQ7...)

This part was a bit clumsy in the report.

even having half a gene, like 05* in the alpha chain, gives higher risk for celiac.

Some labs test only beta chains, some test both, and some do not tell you they tested both until you phone them.

Now to list the children's DQtypes:

to read the charts, in the the first chart only the DQ column is relevant and you can delete the others.

In the second chart, they list the chains in reverse order so it is a bit unusual to read. One must read them DQB1 (beta chain) DQA1 (alpha chain) but it might be easier to read when reversed, alpsha first and beta last.

Daughter 1 has DQ 5 and 6 1.alpha 0101 beta 0501 2.alpha 0102 beta 06*

Son has DQ 5 and 6 same

Daughter 2 has DQ 2 and 5 1. alpha 0101 beta 0201 2. alpha 0501 beta 0501

Daughter 4 has DQ 2 and 5 same See comment

Now that is a bit weird, since DQ2 usually is 0501 0201, and DQ5 is 0101 0501, in linkage disequilibrium. (they like hang around together, like 0501 with 0201 etc. )

Maybe they reported the alleles just in random order? I think so.

I think it should be 1. alpha 0501 beta 0201 2. alpha 0101 beta 0501

Usually reports are easier to read.

Very interesting to see that both alpha and beta chains were done. It happens more and more nowadays. Very good.

There are even at least two forums for gluten sensitive people and many there are DQ5 and 6. They can be more sensitive than regular celiacs...

nora

[elle's mom]

Linkage disequilibrium just means that some alpha and beta chains turn up together way much more often than not. In English: 0501 likes to hang around 0201 (which make up DQ2) etc.

On DQ5 and 6: Dr. Hadjivassiliou has researched gluten ataxia, and written several papers and done gene studies. He found that about 20% of his gluten ataxia patients had DQ1.

(DQ1 are DQ5 and DQ6)

The charts most easy to read for what the alpha and beta chains are, are at

Open Original Shared Link

but to get the DR part you need to look at the DR charts

Open Original Shared Link

Now the thing that might confuse you is the weird wording on the trans DQ2, which they call DR5/DR7 -DQ2. That just simply means the DQ2 molecule is made up from genes from two alleles. Usually the celiac genes are made up from one gene like the normal DQ2 which has 0501 in teh aplha chain and 0201 on the beta chain and DR3. Now trans DQ2 is made up of the non-DR3 DQ2,2 0202 beta chain plus 0505 or 0501 in the alpha chain from DQ7 on the other gene. (Now Enterolab for example does not test for alpha chains and does not report trans DQ2,5 when pepole have DQ2,2 and DQ7...)

This part was a bit clumsy in the report.

even having half a gene, like 05* in the alpha chain, gives higher risk for celiac.

Some labs test only beta chains, some test both, and some do not tell you they tested both until you phone them.

Now to list the children's DQtypes:

to read the charts, in the the first chart only the DQ column is relevant and you can delete the others.

In the second chart, they list the chains in reverse order so it is a bit unusual to read. One must read them DQB1 (beta chain) DQA1 (alpha chain) but it might be easier to read when reversed, alpsha first and beta last.

Daughter 1 has DQ 5 and 6 1.alpha 0101 beta 0501 2.alpha 0102 beta 06*

Son has DQ 5 and 6 same

Daughter 2 has DQ 2 and 5 1. alpha 0101 beta 0201 2. alpha 0501 beta 0501

Daughter 4 has DQ 2 and 5 same See comment

Now that is a bit weird, since DQ2 usually is 0501 0201, and DQ5 is 0101 0501, in linkage disequilibrium. (they like hang around together, like 0501 with 0201 etc. )

Maybe they reported the alleles just in random order? I think so.

I think it should be 1. alpha 0501 beta 0201 2. alpha 0101 beta 0501

Usually reports are easier to read.

Very interesting to see that both alpha and beta chains were done. It happens more and more nowadays. Very good.

There are even at least two forums for gluten sensitive people and many there are DQ5 and 6. They can be more sensitive than regular celiacs...

nora

Nora, you are a wealth of knowledge, God Bless You for all your help. I do not consider myself an ignorant person, but all this genetic stuff is very complicated! Correct me if I'm wrong , but the bottom line from what you're saying is this:

1. My DD#4 is obviously at risk, having the same genes as our diagnosed celiac.

2. My other two children are not in the clear either.

I'm keeping them all gluten free for now anyway. Thanks again.

[nora-n]

Hi, the forums where some very sensitive DQ5 and 6 are, can be found by scrolling down to gluten sensitivity at the braintalk forum and the neruotalk forum.

But of course risk-wise the DQ2's have much more risk for celiac or gluten issues.

Interesting they did all the alpha and beta chains.

I guess it is because the 05* alpha chain even alone is a risk for celiac.

I just ran into this here, where they list DQB1 and DQA1 in that order (the beta chain first, then the alpha chain) so it is not uncommon :

Open Original Shared Link

[nora-n]

I forgot to ask which lab did the gene tests. I am impressed they did all the detailed tests for both the alpha and beta chains.