1. ¹The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
2. ²Department of Clinical Neurology, Radcliffe Infirmary, Oxford, UK
3. ³Department of Medical Genetics and Faculty of Medicine Division of Neurology, University of British Columbia, UBC Hospital, Vancouver, British Columbia, Canada

Correspondence: Professor G Ebers, Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, University of Oxford, Oxford OX2 6HE, UK. E-mail: george.ebers@clneuro.ox.ac.uk

Received 16 February 2006; Revised 20 April 2006; Accepted 20 April 2006; Published online 1 June 2006.

Abstract

Multiple sclerosis (MS) is an autoimmune disease with overwhelming evidence for genetic determination, and for which a maternal parent-of-origin effect has been reported. As with many complex diseases, multiple suggestive linkage signals have been observed. However, the only unambiguous association and linkage identified to date is with alleles of the human lymphocyte antigen (HLA) class II region. We have now carried out high-density microsatellite genotyping for 12 of the most promising regions (1p, 1q, 2q, 4q, 5p, 9q, 10p, 11p, 12q, 17q, 18p, 19p) from a whole-genome scan in 552 affected sibling pairs. This has been carried out in 194 families containing avuncular pairs. These permit examination of parent-of-origin effects in non-colineal pairs when divided into likely maternal and paternal trait transmission. The results do not confirm any non-major histocompatibility complex linkage in the overall subset nor in the maternal, paternal or HLA-DRB1*1501 subsets. We were able to establish exclusion for a locus with _AV1.3 for all the previously suggested regions. These results again raise the possibility that the paradigm of multiple genes of small individual effect used to justify genome searches in MS is incorrect.