caa a22 4500 467986428 CHVBK 20180323112533.0 cr unu---uuuuu 170328e19901201xx s 000 0 eng 10.1007/BF00197702 doi (NATIONALLICENCE)springer-10.1007/BF00197702 Analysis of gene-dosage effects on the expression of CD18 by trisomy 21 lymphoblastoid cell-lines using a statistical model to fit flow cytometry profiles [Elektronische Daten] [W. Bardsley, B. McMurray, A. Robson, S. D'Souza, G. Taylor] Summary: It is not clear whether Down syndrome, the phenotypic expression of constitutional trisomy for chromosome 21 (T21), is the result of generalised disruption of homeostasis resulting from genetic imbalance, or the over-expression of specific genes on chromosome 21. In order to understand the effect of gene dosage more clearly, we have analysed the predicted and actual levels of expression of the leucocyte integrin β subunit CD 18 on the surface of T21 leucocytes. Previous studies showed that CD 18 expression by T21 lymphoid cell lines (LCL) is greater than on normal LCL. We have now developed a computer model that compares the observed and predicted CD 18 flow cytometric profiles for trisomy 21 LCL. Three parameters (α, β and γ) have been defined that measure different aspects of gene dosage. Using the computer model to calculate these parameters, we have carried out a series of paired comparisons between normal and T21 LCL. The results show that, in some T21 LCL, increased CD 18 expression is proportional to the existing gene dosage, in another set the effect is additive, whereas in others there is a combination of proportional and additive effects. The results suggest that gene regulation can exert pleiotropic effects on gene-dosage, and is consistent with a model in which gene dosage itself is the cause of disrupted homeostasis. Springer-Verlag, 1990 Bardsley W. Department of Obstetrics and Gynaecology, St. Mary's Hospital, M13 OJH, Manchester, UK aut McMurray B. Immunogenetics Laboratory, St. Mary's Hospital, M13 OJH, Manchester, UK aut Robson A. Immunogenetics Laboratory, St. Mary's Hospital, M13 OJH, Manchester, UK aut D'Souza S. Department of Child Health, St. Mary's Hospital, M13 OJH, Manchester, UK aut Taylor G. Immunogenetics Laboratory, St. Mary's Hospital, M13 OJH, Manchester, UK aut Human Genetics Springer-Verlag 86/2(1990-12-01), 181-186 0340-6717 86:2<181 1990 86 439 https://doi.org/10.1007/BF00197702 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00197702 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bardsley W. Department of Obstetrics and Gynaecology, St. Mary's Hospital, M13 OJH, Manchester, UK aut NATIONALLICENCE 700 1- McMurray B. Immunogenetics Laboratory, St. Mary's Hospital, M13 OJH, Manchester, UK aut NATIONALLICENCE 700 1- Robson A. Immunogenetics Laboratory, St. Mary's Hospital, M13 OJH, Manchester, UK aut NATIONALLICENCE 700 1- D'Souza S. Department of Child Health, St. Mary's Hospital, M13 OJH, Manchester, UK aut NATIONALLICENCE 700 1- Taylor G. Immunogenetics Laboratory, St. Mary's Hospital, M13 OJH, Manchester, UK aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 86/2(1990-12-01), 181-186 0340-6717 86:2<181 1990 86 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer