title: Familial skewed X-chromosome inactivation linked to a component of the cohesin complex, SA2.
abstract: The gene dosage inequality between females with two X-chromosomes and males with one is compensated for by X-chromosome inactivation (XCI), which ensures the silencing of one X in every somatic cell of female mammals. XCI in humans results in a mosaic of two cell populations: those expressing the maternal X-chromosome and those expressing the paternal X-chromosome. We have previously shown that the degree of mosaicism (the X-inactivation pattern) in a Canadian family is directly related to disease severity in female carriers of the X-linked recessive bleeding disorder, haemophilia A. The distribution of X-inactivation patterns in this family was consistent with a genetic trait having a co-dominant mode of inheritance, suggesting that XCI choice may not be completely random. To identify genetic elements that could be responsible for biased XCI choice, a linkage analysis was undertaken using an approach tailored to accommodate the continuous nature of the X-inactivation pattern phenotype in the Canadian family. Several X-linked regions were identified, one of which overlaps with a region previously found to be linked to familial skewed XCI. SA2, a component of the cohesin complex is identified as a candidate gene that could participate in XCI through its association with CTCF.
authors.affiliation: Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Nisa K E
authors.initials: NK
authors.lastname: Renault
authors.forename: Marc P
authors.initials: MP
authors.lastname: Renault
authors.forename: Emily
authors.initials: E
authors.lastname: Copeland
authors.forename: Robin E
authors.initials: RE
authors.lastname: Howell
authors.forename: Wenda L
authors.initials: WL
authors.lastname: Greer
mesh_terms: D002170:Canada; D018797:Cell Cycle Proteins / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D005169:Factor VIII / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006467:Hemophilia A / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D049951:X Chromosome Inactivation / Q000235:genetics*; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D005169:Factor VIII; D000097722:Cohesins