Analysis of X-chromosome inactivation in X-linked immunodeficiency with hyper-IgM (HIGM1): evidence for involvement of different hematopoietic cell lineages.
The pattern of X-chromosome inactivation was analyzed, by means of two different DNA probes (pSPT-PGK and M27 beta), in several cell lineages derived from females belonging to a pedigree with X-linked immunodeficiency with hyper-IgM (HIGM1). Non-random X-chromosome inactivation was demonstrated in T cells, B cells, and neutrophils, but not in fibroblasts, of obligate carriers, suggesting that different hematopoietic cell lineages are primarily involved in HIGM1. Preferential inactivation of the paternally derived X-chromosome was demonstrated by analysis of segregation of the alleles defined by the pSPT-PGK and M27 beta probes. The possibility that the HIGM1 mutation may confer a proliferative and/or differential advantage to hematopoietic precursors carrying the mutated allele on the active X-chromosome is discussed.
Notarangelo
L D
LD
Dipartimento Materno-Infantile e di Tecnologie Biomediche, Università di Brescia, Italy.
Parolini
O
O
Albertini
A
A
Duse
M
M
Mazzolari
E
E
Plebani
A
A
Camerino
G
G
Ugazio
A G
AG
D001402:B-Lymphocytes; D015342:DNA Probes / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics*; D007075:Immunoglobulin M / Q000097:blood*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008297:Male; D010375:Pedigree; D014960:X Chromosome
D015342:DNA Probes; D007075:Immunoglobulin M