Do bilineal pedigrees represent a problem for linkage analysis? basic principles and simulation results for single-gene diseases with no heterogeneity
✍ Scribed by Dr. Susan E. Hodge; J. J. Mulvihill
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 840 KB
- Volume
- 9
- Category
- Article
- ISSN
- 0741-0395
No coin nor oath required. For personal study only.
✦ Synopsis
Some investigators have expressed concem-zspecially for psychiatric disordersthat bilineal pedigrees should not be included in linkage studies. This study compares the "informativeness" of bilineal and unilineal families for a homogeneous single-gene disorder. Three approaches were used: (1) simulation studies of threegeneration pedigrees, ( 2 ) calculation of expected lod scores (ELODs) in nuclear families, and ( 3 ) calculation of Fisher's information number I(e) in nuclear families. The simulation studies in (1) permitted a realistic comparison between bilineal datasets and purely unilineal ones. The calculations in nuclear families in ( 2 ) and (3) then made it possible to analyze the sources of information loss in bilineal families.
Overall, in datasets of five three-generation pedigrees each, the drop in mean maximum lod score was approximately 50% from purely unilineal datasets to extremely bilineal ones. In less-extreme bilineal datasets, which are closer to most real data than the extremely bilineal ones, the drops in lod score were very smallless than 10% in some, and practically zero in others. The details will vary, depending on size and structure of the pedigree, genetic model, true value of the recombination fraction, and informativeness of the marker. However, these results imply that the information loss due to bilineality is not necessarily very great.
The nuclear-family calculations showed that for phase-known matings there is relatively little information loss in bilineal families, but for phase-unknown matings the loss is much greater.
In conclusion, for single-gene disorders with no genetic heterogeneity, whereas bilineal families can be less informative than comparable unilineal families, they