A Preliminary Study on the Use of Unaffected Siblings for the Marker Allele Frequency of Sib-Pair Linkage Analysis

We have searched the disease-susceptibility genes of rheumatoid arthritis (RA) using fluorescence-based microsatellite marker analysis and affected sib-pair link­ age method. One unaffected sibling was typed in addition to affected sib-pairs, since most parents were not typed due to late onset nature of the disease. In order to verify appropriateness of using unaffected siblings for the calculation of marker allele frequency of the population, we have compared the calculation of marker allele frequency based on unaffected siblings of patient families with that based on unrelated healthy control. Chi-square test showed no statistically signi­ ficant difference between them. It thus appears that unaffected siblings can be used for the calculation of marker allele frequency especially when unaffected siblings are selected carefully by paying attention to the penetrance of disease.