Possible male segregation distortion of DR2 haplotypes in narcolepsy patients

Segregation of disease-associated DR2-linked haplotypes from patients with narcolepsy was studied in 18 German families. Of these, 13 were informative, as transmission could be traced from DR2 heterozygous patients to their healthy offspring. Although the composition of extended haplotypes was equal in males and females, DR2 was transmitted to 78.6% of the offspring by diseased fathers but only to 57.1% by diseased mothers. Compared to an expected 1:1 ratio according to Mendelian segregation this means a statistically significant deviation (p less than or equal to 0.03) for male but not for female patients. In contrast, transmission distortion was not observed with 30 DR2 haplotypes in 27 healthy families. These data represent a new example of male segregation distortion in an HLA-associated disorder.