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Grade-of-membership sibpair linkage analysis maps IDDM11 to chromosome 14q24.3–q31

Published online by Cambridge University Press:  02 October 2001

E. H. CORDER
Affiliation:
The Center for Demographic Studies, 2117 Campus Drive, Duke University, Durham, NC 27701-0408, USA
M. A. WOODBURY
Affiliation:
The Center for Demographic Studies, 2117 Campus Drive, Duke University, Durham, NC 27701-0408, USA
K. G. MANTON
Affiliation:
The Center for Demographic Studies, 2117 Campus Drive, Duke University, Durham, NC 27701-0408, USA
L. L. FIELD
Affiliation:
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
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Abstract

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.

Type
Research Article
Copyright
University College London 2001

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