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#1




The chance of getting homozygous normal HLA compatible sibling for this girl with Tay Sachs!
The parents of a girl with TaySachs 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 HLAcompatible?
a. 1/2 b. 1/3 c. 1/4 d. 1/6 e. 1/12 
#2




the answer should be 1/4

#3




How is the odd of HLA compatibility calcuated in this case?



#4




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.

The above post was thanked by:  
usluipek (07172011) 
#5




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. HLAcompatible? 1/4 (Mendelian fashion) 1/3 * 1/4 = 1/12 How many normal siblings? =3 Answer = 1/12 * 3 = 1/4 
#6




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 ? 
#7




Quote:
chances of being homozygous normal is 1/3... 
#9




Quote:

#11




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 
#12




Quote:
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). 
#13




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 A1B8DR2 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 A9B5DR3 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/ 
#14




but this explanation is different from yours .
Genetic is my weakest area, I dont know from where I can improve it, plz help :sorry: 
#15




Quote:
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... 
#16




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 
#17




Quote:
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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#18




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 
#19




Quote:
Cross of AB and BC will have next progeny AB,AC,BB,BC So 50% will accept the graft from rat A. 
#20




i dont know really but i guess it would be zero coz no AA

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