Enterolab Gene Inheritance

[parker]

I am trying to help someone understand the Enterolab gene testing results. In particular, how the nomenclature works in terms of passing genes from parent to child. I understand each child gets one gene from each parent. I've included the results from this family below (2 parents, 3 children). Using these actual results, how should I interpret this?

i.e., what are the possible gene combinations each child could have inherited? It seems like there would be 4 possible combinations, but I may not understand this fully. I'm also wondering if there is a mistake in the lab results, as 2 children have the Allele 1 0201, but neither parent has this Allele.

Also, Parent 1 was told they have 1 Celiac gene, and all 3 Children have 1 Celiac gene. (Child 1 and Child 2 appear to have the same genetic profile)

Thanks!

Patrick

--------------------

Parent 1:

HLA-DQB1 Molecular analysis, Allele 1 0302

HLA-DQB1 Molecular analysis, Allele 2 0202

Serologic equivalent: HLA-DQ 3,2 (Subtype 8,2)

Parent 2:

HLA-DQB1 Molecular analysis, Allele 1 0503

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 1,1 (Subtype 5,6)

Child 1:

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,6)

Child 2:

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,6)

Child 3:

HLA-DQB1 Molecular analysis, Allele 1 0302

HLA-DQB1 Molecular analysis, Allele 2 0503

Serologic equivalent: HLA-DQ 3,1 (Subtype 8,5)

[parker]

OK, I think I may have finally answered my own question, thanks to the information contained in this link:

HLA DQ Info

If I understood that correctly, then the following possibilities exist for each child:

DQ8/DQ5

DQ8/DQ6

DQ2/DQ5

DQ2/DQ6

Do I have this correct?

Is it also correct that Parent 1 has 2 genes that predispose to Celiac, DQ8 and DQ2?

Thanks!

--------------------

Parent 1:

HLA-DQB1 Molecular analysis, Allele 1 0302

HLA-DQB1 Molecular analysis, Allele 2 0202

Serologic equivalent: HLA-DQ 3,2 (Subtype 8,2)

Parent 2:

HLA-DQB1 Molecular analysis, Allele 1 0503

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 1,1 (Subtype 5,6)

Child 1:

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,6)

Child 2:

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,6)

Child 3:

HLA-DQB1 Molecular analysis, Allele 1 0302

HLA-DQB1 Molecular analysis, Allele 2 0503

Serologic equivalent: HLA-DQ 3,1 (Subtype 8,5)

[lizard00]

okay, genetics is not my strength, BUT i'm a little confused also as to how your kids have the 0201 gene, but neither of you do?

but yes, one parent has the combination gene that predisposes to celiac, along with 2 children.

it should also be noted that we do have a few diagnosed celiacs with dbl dq1, and dq3 as well. dq2 and dq8 are the most widely known and tested for, but not the only linked to celiac.

[fedora]

wow, weird.

so either parent 1's gene 0202 mutated turning into 0201

OR a mistake was made in the lab reading the genes and the parent really has 0201 or the kids really have 0202.

seems like if it is a mistake then it is more likely to be a mistake with parent 1 rather than with the two kids.(because then the mistake happened twice)

I am not sure if the gene could mutate like that.

[parker]

okay, genetics is not my strength, BUT i'm a little confused also as to how your kids have the 0201 gene, but neither of you do?

but yes, one parent has the combination gene that predisposes to celiac, along with 2 children.

it should also be noted that we do have a few diagnosed celiacs with dbl dq1, and dq3 as well. dq2 and dq8 are the most widely known and tested for, but not the only linked to celiac.

I was a little confused as well about 0201, which prompted my question about a possible lab error? Hopefully some enlightened member here will shed some light on this...

Patrick

[Mother of Jibril]

Wikipedia says that serotyping for *0201 is 98% accurate, but for *0202 it's only 87% accurate. So... I would say that your husband and two of your children have *0201, one of the major celiac genes. I don't think a gene can mutate from parent to child.

[Mother of Jibril]

Let me back up for a second there...

I suppose gene mutation is possible. Otherwise, how did the human population end up with all these different DQs? But... I don't think the same mutation would happen twice in two different kids unless you have identical twins.

[nora-n]

Yes, I think there was no mutation, because it would have to have happened twice, but the 0202 result was wrong, and it was 0201, the DQ2,5 gene.

If you read several of the HLA DQ pages (there are several of them, look up DQ2 too) they keep saying some are mistyped, and lab errors occur.

Remember, someone here was tested and negative for DQ8 from Kimball, and they had to send it on to another lab after protests, but Enterolab found it.

[parker]

Although I will follow-up with Enterolab to see what they can tell me, I'm wondering if it really matters, for practical purposes. Is it the case that both 0201 and 0202 both are forms of DQ2, which predisposes to Celiac? If so, it won't change my understanding of the results.

Thanks for any clarification!

Patrick

[nora-n]

The 0202 beta chain in question is only high-risk for celiac if coupled with the alpha chain of DQ7 (05*), because it then makes up 2,5 in trans.

The 0201 in the beta chain has the 0501 alpha chain on the same gene, and encodes DQ2,5 in cis.

The 0202 (2,2) is officcially just a gluten sensitive gene. The alpha chain is 0201.

In plain english, doctors would say it is unlikely the person in question is celiac with a 2,2 gene, but wikipedia says that the 2,2 gene also predisposes somewhat .

Your example is very interesting, since it really proves that mistyping occurs, and that they cannot "prove" we cannot have celiac if the gene test is negative.

The test must be wrong since both the alpha and beta chains are different from the kids' DQ beta 2,5 .

Open Original Shared Link check the chart

nora

[parker]

Yes, I spoke with Enterolab and they indicated there must have been a mistyping. I've put the results of 3 generations below. One of the parents in Family B is a child of Family A. You'll see 3 cases of 0201, and no other cases of 0202. 0202 must be the error. Enterolab is going to have that test run again to confirm.

---------------------

Family A

Parent 1:

HLA-DQB1 Molecular analysis, Allele 1 0302

HLA-DQB1 Molecular analysis, Allele 2 0202

Serologic equivalent: HLA-DQ 3,2 (Subtype 8,2)

DQ8/DQ2

Parent 2:

HLA-DQB1 Molecular analysis, Allele 1 0503

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 1,1 (Subtype 5,6)

DQ5/DQ6

Child 1:

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,6)

DQ2/DQ6

Child 2:

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,6)

DQ2/DQ6

Child 3:

HLA-DQB1 Molecular analysis, Allele 1 0302

HLA-DQB1 Molecular analysis, Allele 2 0503

Serologic equivalent: HLA-DQ 3,1 (Subtype 8,5)

DQ8/DQ5

--------

Family B

Parent 1

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 2,1 (Subtype 2,6)

DQ2/DQ6

Parent 2

HLA-DQB1 Molecular analysis, Allele 1 0301

HLA-DQB1 Molecular analysis, Allele 2 0602

Serologic equivalent: HLA-DQ 3,1 (Subtype 7,6)

DQ7/DQ6

Child 1

HLA-DQB1 Molecular analysis, Allele 1 06xx

HLA-DQB1 Molecular analysis, Allele 2 06xx

Serologic equivalent: HLA-DQ 1,1 (Subtype 6,6)

DQ6/DQ6

Child 2

HLA-DQB1 Molecular analysis, Allele 1 0201

HLA-DQB1 Molecular analysis, Allele 2 0301

Serologic equivalent: HLA-DQ 2,3 (Subtype 2,7)

DQ2/DQ7

[nora-n]

Very interesting about the mistyping.

Looks like the safest thing is to get the whole family tested so one can catch such things, if the results just do not fit.

I am thinking about all of us who tested negative for the two main celiac genes, but who are sure they are celiac. Sometimes the doctors then tell us we cannot be celiac but even the gene tests lie sometimes.

[gfpaperdoll]

Please be careful with the child in family B, that has the double DQ1, that child should be gluten-free. The child may never test positive for gluten but should be gluten-free. Double DQ1, IMO, is not very good because the person will get neurological & other health issues before any gut problems show up, if ever.

My whole family is double DQ1 & has had problems for generations...

not saying that the other people should also be gluten-free, but some people wrongly think that double DQ1 is not a problem...

[darlindeb25]

not saying that the other people should also be gluten-free, but some people wrongly think that double DQ1 is not a problem...

Now that's an understatement if I ever saw one!!!

I have Double DQ, subtype 6 genes, and not only did I develop neurological problems, I also had intestinal problems. Double whammy!!! The intestinal problems came first, to my knowledge. I remember when I was much younger, like my late 20's, with aches and pains, and my mom would say, "You are too young to have aches and pains!" Well, I wasn't too young, I was too "glutened"! I have even had an occasional DH outbreak. No one will ever convince me a double DQ1 can not be celiac.

[parker]

In case anyone is interested, I did finally get clarified what happened with the genetic testing of the family I mentioned previously. Two of the gene tests were done by Enterolab in 2006, and they did not have access to a high resolution method at that time. 0201 genotypes then may have really been 0202, as they could not tell at the time. Now the tests are able to tell the difference between 0201 and 0202. They also did make a transcription error recently in recording the results for this family, so mistakes can and do occur. In any case, if you have the full mapping for a family, you can verify the results yourself. For example, it is true that if 2 parents have these genes:

Parent 1

HLA-DQB1 Molecular analysis, Allele 1 0302

HLA-DQB1 Molecular analysis, Allele 2 0202

Parent 2

HLA-DQB1 Molecular analysis, Allele 1 0503

HLA-DQB1 Molecular analysis, Allele 2 0602

The only 4 possibilities for children would be:

0302, 0503

0302, 0602

0202, 0503

0202, 0602

Most of you probably already know that, but now I've had that verified in my own mind.

Patrick

[nora-n]

Enterolab does not do anye gene testing, but sends it to another lab, and they used to send it to Bonfils, and then this summer people posted they sent it to the Red Cross.

Interesting about that gene tests can lie.

nora

[parker]

Yes, I know they did send it out to another lab. I think saying the tests lie is a little strong, though. It's just that the prior technology (Bonfils, I presume) wasn't able to "see" as much detail, so they could not differentiate between 0201 and 0202. In any case, it's good to know the tests are now more accurate.

The transcription problem is a little more troubling, though, from a test-interpretation standpoint. I would have guessed the results that are created would be fully automated (the testing system generates the text that gets sent to a patient). But clearly somebody is actually typing in "0201" or the like at some point...

Thanks for all your help!

Patrick

[lizard00]

In case anyone is interested, I did finally get clarified what happened with the genetic testing of the family I mentioned previously. Two of the gene tests were done by Enterolab in 2006, and they did not have access to a high resolution method at that time. 0201 genotypes then may have really been 0202, as they could not tell at the time. Now the tests are able to tell the difference between 0201 and 0202. They also did make a transcription error recently in recording the results for this family, so mistakes can and do occur. In any case, if you have the full mapping for a family, you can verify the results yourself.

Patrick

So did Enterolab retest the family, or did they offer clarification on why there was a difference between parents not having the gene and children having it?

Because I would imagine a retest would be better to clarify where the mistake was made.

[parker]

Enterolab retested the most recent member of the family that had the 0202 gene (that was tested a couple of months ago), to confirm the results. 0202 or 0201, avoiding gluten will happen in either case.