Nonrandom inactivation of the X chromosome in early lineage hematopoietic cells in carriers of Wiskott-Aldrich syndrome.
The Wiskott-Aldrich syndrome (WAS) is an X-linked (Xp11.22) recessive immunodeficiency syndrome characterized by susceptibility to opportunistic and pyogenic infections, thrombocytopenia, and eczema. Previous studies of obligate carriers of WAS documented that nonrandom inactivation of the X chromosome carrying the defective gene is observed in all peripheral blood cells. The existence of both abnormal platelets and lymphocytes is consistent with a defect that affects early hematopoietic precursors. We isolated CD34+ hematopoietic progenitor cells collected from obligate carriers of WAS by apheresis and used polymerase chain reaction analysis of a polymorphic variable number of repeats (VNTR) within the X-linked androgen receptor to document nonrandom inactivation. These data show that nonrandom inactivation of the X-chromosome in WAS-obligate carriers occurs early during hematopoietic differentiation.
Wengler
G
G
Center for Blood Research, Children's Hospital, Boston, MA, USA.
Gorlin
J B
JB
Williamson
J M
JM
Rosen
F S
FS
Bing
D H
DH
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001483:Base Sequence; D001773:Blood Cells / Q000648:ultrastructure*; D004303:Dosage Compensation, Genetic; D005260:Female; D006412:Hematopoietic Stem Cells / Q000648:ultrastructure*; D006579:Heterozygote; D006801:Humans; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics* / Q000473:pathology
D015703:Antigens, CD; D018952:Antigens, CD34; D011944:Receptors, Androgen