We demonstrate the use of Grade-of-membership (GoM) (Manton et al. 1994) for sibpair linkage
analysis: GoM was used to map the IDDM11 locus to the region of chromosome 14q24.3 identified
by Field et al. (1996). Haplotype groups were constructed from sib pair information on the number
of shared alleles. The sample consisted of 578 sibling pairs found in 246 multiplex IDDM families.
Both siblings were diabetic in 53% of the pairs (AA). Pair members could share 0, 1 or 2 alleles IBS
at each of eight linked marker loci spanning IDDM11. Three model-based groups best represented the
data on allele sharing: the groups corresponded to ‘No’, ‘One’ and ‘Two’ shared
haplotypes for the region. Group ‘Two’ was larger (37% vs. 25%, p<0.0001)
and more homogeneous (p<0.0001) than
expected by chance consistent with the IDDM11 locus being a determinant of diabetes in multiplex
families. Genetic linkage of IDDM to the region was demonstrated by a 19% increase in the
proportion of AA pairs over the haplotype groups: ‘No’, 42%; ‘One’, 49%; ‘Two’,
61%, p = 0.0005, representing a 43% relative increase.