Linkage analysis conditional on HLA status in a large North American pedigree supports the presence of a multiple sclerosis susceptibility locus on chromosome 12p12

Emilia Vitale, Stuart Cook, Rong Sun, Claudia Specchia, Kavitha Subramanian, Mariano Rocchi, Douglas Nathanson, Marvin Schwalb, Marcella Devoto, Christine Rohowsky-Kochan

Research output: Contribution to journalArticle

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a probable immune-mediated pathogenesis. Strong evidence supports the hypothesis that MS is determined by genetic and environmental factors, but these factors remain largely undefined. The genetic component is suggested by a higher concordance rate in monozygotic (28%) versus dizygotic (5%) twins as well as familial recurrence risk. Several studies have shown association of MS with the histocompatibility leukocyte antigen (HLA) class II region, specifically DR15, DQ6. However, there is no convincing evidence of a common susceptibility locus. We have identified a pedigree of Pennsylvania Dutch extraction, in which MS segregates with an autosomal dominant inheritance pattern. We have collected blood samples from 18 family members, seven of whom show typical signs of MS lesions by magnetic resonance imaging. The 18 individuals were serotyped for HLA class I and II and analyzed by a genome-wide screen for linkage analysis. We have found evidence for suggestive linkage to markers on 12p12 with a maximum multipoint LOD score of 2.71, conditional on the presence of DR15, DQ6. Contingency table analysis showed that all MS affected individuals have both the DR15, DQ6 allele and the 12p12 haplotype whereas the unaffected individuals have either one or neither of these markers (P = 0.00011). Our data suggests that both HLA DR15, DQ6 and a novel locus on chromosome 12p12 may be necessary for development of MS in this family.

Original languageEnglish
Pages (from-to)295-300
Number of pages6
JournalHuman Molecular Genetics
Volume11
Issue number3
Publication statusPublished - Feb 1 2002

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Linkage analysis conditional on HLA status in a large North American pedigree supports the presence of a multiple sclerosis susceptibility locus on chromosome 12p12'. Together they form a unique fingerprint.

  • Cite this

    Vitale, E., Cook, S., Sun, R., Specchia, C., Subramanian, K., Rocchi, M., Nathanson, D., Schwalb, M., Devoto, M., & Rohowsky-Kochan, C. (2002). Linkage analysis conditional on HLA status in a large North American pedigree supports the presence of a multiple sclerosis susceptibility locus on chromosome 12p12. Human Molecular Genetics, 11(3), 295-300.