Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004 May;114(6):588-93.
doi: 10.1007/s00439-004-1109-7. Epub 2004 Mar 26.

Quasi-linkage: A Confounding Factor in Linkage Analysis of Complex Diseases?


Quasi-linkage: A Confounding Factor in Linkage Analysis of Complex Diseases?

Sinthuja Sivagnanasundaram et al. Hum Genet. .


Human linkage analysis is based on the assumption that unlinked genomic loci, particularly loci located on non-homologous chromosomes, segregate independently during meiosis. An exception to this rule is the phenomenon of quasi-linkage (QL) that describes the non-random segregation of non-homologous chromosomes, which can undermine the basic concept of linkage. Molecular mechanisms of QL are not clear; however, observations in mice and plants suggest a possible affinity between non-homologous chromosomal regions containing repetitive or like sequences. QL has not been investigated in humans. As QL may generate false linkages in genome scans of complex diseases, we sought to determine whether genomic loci detected in such genome scans exhibit QL. A number of individual markers showing linkage to schizophrenia, asthma, multiple sclerosis, inflammatory bowel disease and type-1 diabetes were tested for QL in a pairwise linkage analysis against all other markers exhibiting evidence for linkage in each specific study. The Marshfield genotype dataset of eight CEPH families was used for this purpose. The best QL lod scores generated from the analysis were within the range of the "lukewarm" lod scores reported in the majority of linkage studies for complex disorders. In addition, we performed a genome-wide QL analysis on the Marshfield family database which detected eight QL lod scores >6. The replication of the best Marshfield QL scores was performed using the deCODE families and although none of the eight pairs demonstrated independent evidence for QL, three pairs generated maximal lod scores of 0.11, 0.3, and 1.51. In conclusion, although complex disease relevant markers did not produce high QL lod scores, the general phenomenon of QL in humans cannot be excluded and potentially can be a confounding factor in genetic studies of complex traits.

Similar articles

See all similar articles

Cited by 3 articles


    1. Nat Genet. 1996 Aug;13(4):472-6 - PubMed
    1. Chromosoma. 1971;34(1):73-87 - PubMed
    1. Nat Genet. 1998 Jul;19(3):292-6 - PubMed
    1. Am J Hum Genet. 1998 Sep;63(3):861-9 - PubMed
    1. Cytogenetics. 1964;3:124-34 - PubMed

Publication types

LinkOut - more resources