Heterogeneity among the spinocerebellar ataxias (SCA) has been shown on clinical, biochemical, and genetic criteria. Among the autosomal dominant SCAs, several kindreds have shown loose linkage to the HLA loci on chromosome 6, while linkage in other kindreds has been rejected. The advent of multipoi
Multipoint linkage analysis for a very dense set of markers
โ Scribed by Silviu-Alin Bacanu
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 113 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0741-0395
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โฆ Synopsis
Abstract
Multipoint linkage methods are powerful tools that are often employed as the first means to discover alleles affecting liability to diseases. With the advent of dense marker maps, linkage disequilibrium (LD) between markers is inevitable and it comes at the cost of bias and an increased rate of falseโpositive findings for linkage analyses that assume alleles of different markers are independent. I propose a โmultipoint on subsetsโ method that avoids this issue by partitioning the markers into interlaced and nonโoverlapping subsets. Each subset is analyzed separately, their statistics are then averaged, and the resulting average is standardized by its estimated standard deviation. In addition to being robust to the challenges induced by dependent marker alleles, data simulated under linkage equilibrium show that the proposed method does not suffer any detectable loss of power when compared to traditional methods. Genet. Epidemiol. 2005. ยฉ 2005 WileyโLiss, Inc.
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