Vol.20 No.4

Original Article

Mathematical basis of affected sib-pair analysis: an extension to X-linked loci

Authors

Yasuo Tsukamoto1 , Koichiro Komai2 , Ken Tsumiyama2 , Yoshitada Sakai3 , Shunichi Shiozawa3

  • Information Science and Technology Center, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan
  • Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan
  • Department of Medicine and The Center for Rheumatic Diseases, Kobe University Hospital, Kobe, Japan
Received:

29 September 2009

Accepted:

22 February 2010

Published online:

1 May 2010

Full Text

PDF　(member's only)

Abstract

Most clinical genetic studies are done without knowing their mathematical basis. However, because the results of such studies rely on the correctness of the mathematical calculations involved, we cannot ignore the mathematics of genetic studies. In this study, the mathematical basis of the sib-pair method, which has been widely used in recent genome-wide studies, was extended to studies focusing on the X chromosome, and then applied to study a clinical microsatellite marker on the X chromosome. Our calculation involves classifying marker types on the X chromosome for an affected sib-pair and an unaffected sib, together with their sexual information and the possible parental marker types applicable to a genome-wide genetic study. The method proposed in this study was then applied to 41 Japanese rheumatoid families, and the locus DXS984 was found to be most likely to be linked with rheumatoid arthritis (RA). This locus, which we found nicely, was also highlighted in a previous study that used the Mapmaker/sibs program, so we can conclude that our calculation provides a solid foundation for understanding and confirming the results obtained using the sib-pair method.

Key words

Affected sib-pair method - Likelihood - Linkage analysis - X-linked locus