A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations
Artikel i vetenskaplig tidskrift, 2015

Several applications necessitate an unbiased determination of relatedness, be it in linkage or association studies or in a forensic setting. An appropriate model to compute the joint probability of some genetic data for a set of persons given some hypothesis about the pedigree structure is then required. The increasing number of markers available through high-density SNP microarray typing and NGS technologies intensifies the demand, where using a large number of markers may lead to biased results due to strong dependencies between closely located loci, both within pedigrees (linkage) and in the population (allelic association or linkage disequilibrium (LD)). We present a new general model, based on a Markov chain for inheritance patterns and another Markov chain for founder allele patterns, the latter allowing us to account for LD. We also demonstrate a specific implementation for X chromosomal markers that allows for computation of likelihoods based on hypotheses of alleged relationships and genetic marker data. The algorithm can simultaneously account for linkage, LD, and mutations. We demonstrate its feasibility using simulated examples. The algorithm is implemented in the software FamLinkX, providing a user-friendly GUI for Windows systems (FamLinkX, as well as further usage instructions, is freely available at www.famlink.se). Our software provides the necessary means to solve cases where no previous implementation exists. In addition, the software has the possibility to perform simulations in order to further study the impact of linkage and LD on computed likelihoods for an arbitrary set of markers.

Mutation

Markov-chain

Linkage

X chromosome

Lander-Green

FamLinkX

Likelihood computations

Författare

Daniel Kling

Norwegian Institute of Public Health

Universitetet for miljo- og biovitenskap

Andreas O Tillmar

Linköpings universitet

Thore Egeland

Universitetet for miljo- og biovitenskap

Norwegian Institute of Public Health

Petter Mostad

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

International Journal of Legal Medicine

0937-9827 (ISSN) 1437-1596 (eISSN)

Vol. 129 943-954

Ämneskategorier

Rättsmedicin

DOI

10.1007/s00414-014-1117-7