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Interaction Between Two Quantitative Trait Loci Affects Fetal Haemoglobin Expression
Author(s) -
Garner C.,
Menzel S.,
Martin C.,
Silver N.,
Best S.,
Spector T. D.,
Thein S. L.
Publication year - 2005
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1529-8817.2005.00188.x
Subject(s) - quantitative trait locus , biology , epistasis , genetics , expression quantitative trait loci , phenotype , trait , genotype , evolutionary biology , gene , single nucleotide polymorphism , computer science , programming language
Summary The biological mechanisms controlling complex quantitative traits are likely to be affected by interactions between genetic factors, sometimes referred to as epistasis. The identification of interacting loci through genetic analyse faces many challenges, and few examples of replicated findings of interaction exist for humans and model system organisms. The replication of an interaction, or the non‐independence, of two quantitative trait loci (QTL) affecting the developmental switch from the expression of fetal to adult haemoglobin is reported here. Fetal haemoglobin expression in adults is a highly heritable, yet complex, phenotype. Using a sample of 874 dizygotic twin pairs of European descent, we found linkage to a QTL on chromosome 8 to be conditional on the twin pairs' genotypes at a polymorphism in the β‐globin complex; an interaction originally identified in a large Asian Indian kindred. The β‐globin polymorphism has been previously shown to be associated with fetal haemoglobin levels in adults. This study reports the first known replication of a genetic interaction between QTLs influencing a complex human trait.