Related Experiment Video
Updated: May 12, 2026

Detection of Rare Genomic Variants from Pooled Sequencing Using SPLINTER
Published on: June 23, 2012
Using affected sib-pairs to uncover rare disease variants
Hervé Perdry1, Bertram Müller-Myhsok, Françoise Clerget-Darpoux
1Université Paris-Sud, Villejuif, France. herve.perdry@u-psud.fr
Objective:
We propose a new test for rare variant mapping, based on an affected sib-pair sample and a control sample. In each sib-pair, only the index case needs to be sequenced, and the number of alleles shared identical-by-descent between the sibs is used as complementary information. The test makes use of both association and linkage information. We compare this test to the Armitage test on case-control data, with cases either from the general population of cases or from a sample of cases having an affected sib.
Methods:
A score test based on the likelihood in a multiplicative risk model is proposed. Its power is estimated by simulations and compared to Armitage test's power.
Results:
The affected sib-pairs design allows a tremendous gain of power over the case-control design (from 1 to 99% for a moderate sample size and relative risk values around 3, at an α level of 10(-11)). When cases are ascertained in a sample of cases having an affected sib, the use of linkage information in our test allows a gain of power of more than 20% in certain situations.
Conclusion:
We demonstrate the interest in using familial data and both association and linkage information for rare variant mapping.
Related Concept Videos
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Pedigree Analysis
Pharmacogenomics: Identification of New Drug Targets
Single Nucleotide Polymorphisms-SNPs
Pleiotropy
Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...

