title: Long-term balancing selection at the blood group-related gene B4galnt2 in the genus Mus (Rodentia; Muridae).
abstract: Recent surveys of the human genome have highlighted the significance of balancing selection in relation to understanding the evolutionary origins of disease-associated variation. Cis-regulatory variation at the blood group-related glycosyltransferase B4galnt2 is associated with a phenotype in mice that closely resembles a common human bleeding disorder, von Willebrand disease. In this study, we have performed a survey of the 5' flanking region of the B4galnt2 gene in several Mus musculus subspecies and Mus spretus. Our results reveal a clear pattern of trans-species polymorphism and indicate that allele classes conferring alternative tissue-specific expression patterns have been maintained for >2.8 My in the genus Mus. Furthermore, analysis of B4galnt2 expression patterns revealed the presence of an additional functional class of alleles, supporting a role for gastrointestinal phenotypes in the long-term maintenance of expression variation at this gene.
authors.affiliation: Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Linnenbrink
authors.forename: Jill M
authors.initials: JM
authors.lastname: Johnsen
authors.forename: Inka
authors.initials: I
authors.lastname: Montero
authors.forename: Christine R
authors.initials: CR
authors.lastname: Brzezinski
authors.forename: Bettina
authors.initials: B
authors.lastname: Harr
authors.forename: John F
authors.initials: JF
authors.lastname: Baines
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D016000:Cluster Analysis; D019143:Evolution, Molecular; D041981:Gastrointestinal Tract / Q000378:metabolism; D014644:Genetic Variation; D015810:Linkage Disequilibrium; D051379:Mice / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity
chemical_list: D017350:N-Acetylgalactosaminyltransferases; C071413:beta-1,4-N-acetyl-galactosaminyl transferase 2