allele numbering

Jonathan L. Haines HAINES at HELIX.MGH.HARVARD.EDU
Thu Jul 7 20:17:36 EST 1994


This is a recurring problem that has been vexing the genetic linkage
community for many years.  The basic problem is to preserve the genetic/
segregation information while reducing the number of alleles to a range
that allows easy computation.  The method of recoding (recycling) alleles
described by Ott (AJHG, 1978) works very well, but can only be done when
the mode of inheritance of the disease is known (thus allowing the recoding
of spouses).  In a complex disorder, this may not be possible.  If the marker
in question has 14 alleles in the general population, but only 9 alleles
in the study population, it is possible to reduce the functional number of
alleles to 9 or 10.  For the former, we usually adjust the allele
frequencies to sum to 1 by dividng each allele freqeucny by the sum of
the (observed) allele frequencies.  For the latter, all the allele
frequencies remain the same, but the unobserved ones are collapsed into
a single allele (and frequency).
     Of course, for a complex disorder, lod scores may also not be the
best choice for screening, since it assumes a mode of inheritance.  Non
parametric methods are not restricted by the number of alleles, or by
mode of inheritance.  The usual caveats about the sensitivity of results
to allele frequency assumptuions (among many others!) apply.

Jonathan Haines



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