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  #1  
Old 07-17-2011
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Genetics The chance of getting homozygous normal HLA compatible sibling for this girl with Tay Sachs!

The parents of a girl with Tay-Sachs disease decide to pursue bone marrow transplantation in an attempt to provide a source for the missing lysosomal enzyme. Preliminary testing of the girl's normal siblings is performed to assess their carrier status and their human leukocyte antigen (HLA) locus compatibility with their affected sister. What is the chance that one of the three siblings is homozygous normal (i.e., has a good supply of enzyme) and HLA-compatible?

a. 1/2
b. 1/3
c. 1/4
d. 1/6
e. 1/12
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Old 07-17-2011
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the answer should be 1/4
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Old 07-17-2011
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How is the odd of HLA compatibility calcuated in this case?
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Quote:
Originally Posted by usluipek View Post
How is the odd of HLA compatibility calcuated in this case?
The entire MHC is inherited as an HLA haplotype in a Mendelian fashion from each parent. So, two siblings have a 25% chance of being genotypically HLA identical, a 50% chance of being HLA haploidentical (sharing one haplotype), and a 25% chance that they share no HLA haplotypes.
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Old 07-17-2011
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So,
Father Aa
Mother Aa
AA Aa Aa aa

1.-What is the chance that one of the three siblings is homozygous normal?
1/3 (because we know that they don't have TS)

2.- HLA-compatible? 1/4 (Mendelian fashion)

1/3 * 1/4 = 1/12

How many normal siblings? =3

Answer = 1/12 * 3 = 1/4
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  #6  
Old 07-17-2011
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Hi, Bebix, thanks! can you pls explain how you reach the conclusion?

So,

chances of being homozygous normal is 1/4
and
chances of being HLA compatible is 1/4

So shouldn't the answer be 1/4 x 1/4 = 1/16 ?
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Old 07-17-2011
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Quote:
Originally Posted by usluipek View Post
Hi, Bebix, thanks! can you pls explain how you reach the conclusion?

So,

chances of being homozygous normal is 1/4
and
chances of being HLA compatible is 1/4

So shouldn't the answer be 1/4 x 1/4 = 1/16 ?
check the post #5
chances of being homozygous normal is 1/3...
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Old 07-17-2011
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OK, Bebix, never mind. Your post explains it perfectly. Thanks a million........
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  #9  
Old 07-18-2011
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Quote:
Originally Posted by bebix View Post
So,
Father Aa
Mother Aa
AA Aa Aa aa

1.-What is the chance that one of the three siblings is homozygous normal?
1/3 (because we know that they don't have TS)

2.- HLA-compatible? 1/4 (Mendelian fashion)

1/3 * 1/4 = 1/12

How many normal siblings? =3

Answer = 1/12 * 3 = 1/4
BEBIX AFTER GETTING 1/12......WHY HAVE U MULTIPLY BY 3??.....PLS EXPLAIN...THANX IN ADVANCE....QUESTION HAS ASKED ABOUT CHACE OF HOMOZYGOUS NORMAL AND HLA COMPATIBLE!!!
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Old 07-18-2011
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Quote:
Originally Posted by dr.digant View Post
BEBIX AFTER GETTING 1/12......WHY HAVE U MULTIPLY BY 3??.....PLS EXPLAIN...THANX IN ADVANCE....QUESTION HAS ASKED ABOUT CHACE OF HOMOZYGOUS NORMAL AND HLA COMPATIBLE!!!
Because they are asking for the probability that one of the three siblings is homozygous normal and HLA-compatible.
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  #11  
Old 07-20-2011
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Default correct answer EE

Hi bebix,

Thank you for your answer,
the first part was correct,
here their answer:

chance of being homozygous normal = 1/3 chance of having same HLA pattern as sibling = 1/4 chance of having both together = 1/3 * 1/4 = 1/12 2 siblings who inherit the same two HLA chromosomes (haplotypes) from their parents will be HLA identical. There is a one in four chance that this will occur=1/4 chance of being homozygous normal = 1/3 1/4^1/3=1/12
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Old 07-20-2011
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Quote:
Originally Posted by laurier View Post
Hi bebix,

Thank you for your answer,
the first part was correct,
here their answer:

chance of being homozygous normal = 1/3 chance of having same HLA pattern as sibling = 1/4 chance of having both together = 1/3 * 1/4 = 1/12 2 siblings who inherit the same two HLA chromosomes (haplotypes) from their parents will be HLA identical. There is a one in four chance that this will occur=1/4 chance of being homozygous normal = 1/3 1/4^1/3=1/12
where did you find this question?

This is a probability question. If they ask the probability of 1 of the 3, you must multiple 1/12 x 3 (they are independent).
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Old 07-20-2011
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btw, I found the same question in another forum (2005)...the answer also was 1/4 and here is the explanation (more elaborate than mine though, haha)..this is just probability theory

"Well the answer given is..1/4 and the explanation is...

tay sachs is AR , if the girl has tay sachs it means both parents r carriers(Aa and Aa)
now 4 possibilities wud be AA, Aa, Aa, aa. girl's normal siblings wud either be carriers or homozygous normal, so, we r left with 3 options Either Aa or Aa or AA. out of these 3, AA is homozygous normal, so chances of her sibling being homozygous normal is 1/3

now coming to 2nd part of the q , 2 sibs wud be HLA compatible if they inherit same chromosomes . if the pt got allele with A1-B8-DR2 frm the father , the chances of other sibling getting the same chr from father are 50%(1/2)

AND if pt has got ch with A9-B5-DR3 from mother then the chance of that sib getting same ch frm mother is 50% , the chances of inheriting same parental ch r 1/2*1/2 = 1/4
so, the chances of being homozygous normal and HLA compatible r 1/3*1/4 = 1/12
chances of one of the 3 siblings being homozygous normal and HLA compatible r 1/12 +1/12+1/12 =1/4"

http://www.prep4usmle.com/forum/thread/27941/
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Old 07-20-2011
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but this explanation is different from yours .

Genetic is my weakest area, I dont know from where I can improve it,
plz help :sorry:
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  #15  
Old 07-20-2011
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Quote:
Originally Posted by laurier View Post
but this explanation is different from yours .

Genetic is my weakest area, I dont know from where I can improve it,
plz help :sorry:
the explanation is the same!!! (see post #5)

both ways you should get 1/4

- For the HLA I used 1/4 (both parents), and they used 1/2 * 1/2...which is also 1/4...
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Old 07-21-2011
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hi bebix i want to ask something if u dont mind
like we know HLA are six groups right? and i thought like HLA A inheritance for example is independent from HLA B and other HLA so if it is as u said 1/4 then i guess that means HLA will be inherited all together so it becomes as Autosomal Recessive
please explain if u can and thx
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Old 07-21-2011
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Quote:
Originally Posted by dr.muhamad View Post
hi bebix i want to ask something if u dont mind
like we know HLA are six groups right? and i thought like HLA A inheritance for example is independent from HLA B and other HLA so if it is as u said 1/4 then i guess that means HLA will be inherited all together so it becomes as Autosomal Recessive
please explain if u can and thx
This is how:
The chance of getting homozygous normal HLA compatible sibling for this girl with Tay Sachs!-hla.jpg

Please read this article.
The HLA System: Genetics, Immunology, Clinical Testing, and Clinical Implications
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2628004/
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Old 12-09-2011
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Hi Bebix, Thanks for clearing up some of my confusion regarding HLA and its inheritance. I am stuck with another question regarding this, can u help me out with this? Thanks.

Rat A, B and C differ in one allele in HLA locus. They are crossed with each other. What percent of offspring obtained from the cross of (AXB) X (BXC) will accept graft from rat A?
a 25%
b 50%
c 75%
d 100%
e 0%

I can't make anything out of this. Can anyone help me? :S
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Old 12-09-2011
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Quote:
Originally Posted by ispy View Post
Hi Bebix, Thanks for clearing up some of my confusion regarding HLA and its inheritance. I am stuck with another question regarding this, can u help me out with this? Thanks.

Rat A, B and C differ in one allele in HLA locus. They are crossed with each other. What percent of offspring obtained from the cross of (AXB) X (BXC) will accept graft from rat A?
a 25%
b 50%
c 75%
d 100%
e 0%

I can't make anything out of this. Can anyone help me? :S

Cross of AB and BC will have next progeny AB,AC,BB,BC

So 50% will accept the graft from rat A.
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Old 12-09-2011
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Quote:
Originally Posted by aknz View Post
Cross of AB and BC will have next progeny AB,AC,BB,BC

So 50% will accept the graft from rat A.
i dont know really but i guess it would be zero coz no AA
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