unusual inheritance of disease susceptibility

Peter Rice pmr at sanger.ac.uk
Wed Jun 21 04:10:05 EST 1995

In article <morahan-1706951501580001 at mac174.wehi.edu.au> morahan at wehi.edu.au (Grant Morahan) writes:
>   We have been analysing genetic susceptibility to an experimentally-induced
>   disease in mice.  The results are surprising. 
>   Inbred strain A -100% susceptible;
>   inbred strain B -100% resistant. 
>   (AxB)F1  - 50% are susceptible.  
>   F2 -  25% are susceptible. So far, so good.
>   But 50% of the ((AxB)xA)BC1 mice develop disease.
>   (We don't have results for the reciprocal BC yet). 
>   The problem is that the BC doesn't seem more susceptible than the F1.
>   Can anyone suggest a genetic model to explain these results? We haven't
>   been able to come up with one.
>   Any suggestions would be welcome.

Hmmm. How about this:

Strain A  Strain B

   Xx        xx
 (susc)    (rest)

(AxB)F1 will be:

   50%       50%
   Xx        xx
 (susc)    (rest)

F2 will be:

   75%       25%
   Xx        xx
 (susc)    (rest)

((AxB)xA) will be:

  12.5%   50%     37.5%
   XX     Xx       xx
 (????) (susc)  (rest)

so we can get your result by suggesting that the XX phenotype is resistant
and that only the heterozygotes are susceptible to the disease.

What do you get from other backcrosses? BC1 would be the only one to
generate the XX genotype in the results so far.

Then again, I may be completely wrong ...
Peter Rice                           | Informatics Division
E-mail: pmr at sanger.ac.uk             | The Sanger Centre
Tel: (44) 1223 494967                | Hinxton Hall, Hinxton,
Fax: (44) 1223 494919                | Cambs, CB10 1RQ
URL: http://www.sanger.ac.uk/~pmr/   | England

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