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Title: Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice

Abstract

Genetic factors affecting post-natal g-globin expression - a major modifier of the severity of both b-thalassemia and sickle cell anemia, have been difficult to study. This is especially so in mice, an organism lacking a globin gene with an expression pattern equivalent to that of human g-globin. To model the human b-cluster in mice, with the goal of screening for loci affecting human g-globin expression in vivo, we introduced a human b-globin cluster YAC transgene into the genome of FVB mice . The b-cluster contained a Greek hereditary persistence of fetal hemoglobin (HPFH) g allele resulting in postnatal expression of human g-globin in transgenic mice. The level of human g-globin for various F1 hybrids derived from crosses between the FVB transgenics and other inbred mouse strains was assessed. The g-globin level of the C3HeB/FVB transgenic mice was noted to be significantly elevated. To map genes affecting postnatal g-globin expression, a 20 centiMorgan (cM) genome scan of a C3HeB/F VB transgenics [prime] FVB backcross was performed, followed by high-resolution marker analysis of promising loci. From this analysis we mapped a locus within a 2.2 cM interval of mouse chromosome 1 at a LOD score of 4.2 that contributes 10.4% of variationmore » in g-globin expression level. Combining transgenic modeling of the human b-globin gene cluster with quantitative trait analysis, we have identified and mapped a murine locus that impacts on human g-globin expression in vivo.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
National Institutes of Health (US)
OSTI Identifier:
773782
Report Number(s):
LBNL-45336
R&D Project: 807J12; TRN: AH200106%%205
DOE Contract Number:  
AC03-76SF00098
Resource Type:
Journal Article
Journal Name:
Mammalian Genome
Additional Journal Information:
Journal Volume: 11; Journal Issue: 11; Other Information: PBD: 1 Mar 2000
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CHROMOSOMES; GENES; GENETICS; GLOBINS; HEMOGLOBIN; IN VIVO; MICE; SICKLE CELL ANEMIA; STRAINS; TRANSGENIC MICE

Citation Formats

Lin, S D, Cooper, P, Fung, J, Weier, H U.G., and Rubin, E M. Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice. United States: N. p., 2000. Web. doi:10.1007/s003350010164.
Lin, S D, Cooper, P, Fung, J, Weier, H U.G., & Rubin, E M. Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice. United States. https://doi.org/10.1007/s003350010164
Lin, S D, Cooper, P, Fung, J, Weier, H U.G., and Rubin, E M. 2000. "Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice". United States. https://doi.org/10.1007/s003350010164.
@article{osti_773782,
title = {Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice},
author = {Lin, S D and Cooper, P and Fung, J and Weier, H U.G. and Rubin, E M},
abstractNote = {Genetic factors affecting post-natal g-globin expression - a major modifier of the severity of both b-thalassemia and sickle cell anemia, have been difficult to study. This is especially so in mice, an organism lacking a globin gene with an expression pattern equivalent to that of human g-globin. To model the human b-cluster in mice, with the goal of screening for loci affecting human g-globin expression in vivo, we introduced a human b-globin cluster YAC transgene into the genome of FVB mice . The b-cluster contained a Greek hereditary persistence of fetal hemoglobin (HPFH) g allele resulting in postnatal expression of human g-globin in transgenic mice. The level of human g-globin for various F1 hybrids derived from crosses between the FVB transgenics and other inbred mouse strains was assessed. The g-globin level of the C3HeB/FVB transgenic mice was noted to be significantly elevated. To map genes affecting postnatal g-globin expression, a 20 centiMorgan (cM) genome scan of a C3HeB/F VB transgenics [prime] FVB backcross was performed, followed by high-resolution marker analysis of promising loci. From this analysis we mapped a locus within a 2.2 cM interval of mouse chromosome 1 at a LOD score of 4.2 that contributes 10.4% of variation in g-globin expression level. Combining transgenic modeling of the human b-globin gene cluster with quantitative trait analysis, we have identified and mapped a murine locus that impacts on human g-globin expression in vivo.},
doi = {10.1007/s003350010164},
url = {https://www.osti.gov/biblio/773782}, journal = {Mammalian Genome},
number = 11,
volume = 11,
place = {United States},
year = {Wed Mar 01 00:00:00 EST 2000},
month = {Wed Mar 01 00:00:00 EST 2000}
}