Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation

被引：57

作者：

Milani, Lili ^{[1
]}

Lundmark, Anders ^{[1
]}

Nordlund, Jessica ^{[1
]}

Kiialainen, Anna ^{[1
]}

Flaegstad, Trond ^{[2
]}

Jonmundsson, Gudmundur ^{[3
]}

Kanerva, Jukka ^{[4
]}

Schmiegelow, Kjeld ^{[5
,6
]}

Gunderson, Kevin L. ^{[7
]}

Lonnerholm, Gudmar ^{[8
]}

Syvanen, Ann-Christine ^{[1
]}

机构：

[1] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden

[2] Univ & Univ Hosp, Dept Pediat, N-9038 Tromso, Norway

[3] Landspitalinn, Dept Pediat, IS-101 Reykjavik, Iceland

[4] Univ Helsinki, Div Hematol Oncol & Stem Cell Transplantat, Hosp Children & Adolescents, Hus Helsinki 00029, Finland

[5] Univ Copenhagen, Pediat Clin 2, Rigshosp, DK-2100 Copenhagen, Denmark

[6] Univ Copenhagen, Fac Med, Inst Gynecol Obstet & Pediat, DK-2100 Copenhagen, Denmark

[7] Illumina Inc, San Diego, CA 92121 USA

[8] Univ Childrens Hosp, Dept Womens & Childrens Hlth, S-75185 Uppsala, Sweden

来源：

GENOME RESEARCH | 2009年 / 19卷 / 01期

基金：

瑞典研究理事会;

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; DIFFERENTIAL EXPRESSION; CHILDHOOD; NUCLEOTIDE; IMPACT;

D O I：

10.1101/gr.083931.108

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To identify genes that are regulated by cis-acting functional elements in acute lymphoblastic leukemia (ALL) we determined the allele-specific expression (ASE) levels of 2529 genes by genotyping a genome-wide panel of single nucleotide polymorphisms in RNA and DNA from bone marrow and blood samples of 197 children with ALL. Using a reproducible, quantitative genotyping method and stringent criteria for scoring ASE, we found that 16% of the analyzed genes display ASE in multiple ALL cell samples. For most of the genes, the level of ASE varied largely between the samples, from 1.4-fold overexpression of one allele to apparent monoallelic expression. For genes exhibiting ASE, 55% displayed bidirectional ASE in which overexpression of either of the two SNP alleles occurred. For bidirectional ASE we also observed overall higher levels of ASE and correlation with the methylation level of these sites. Our results demonstrate that CpG site methylation is one of the factors that regulates gene expression in ALL cells.

引用

页码：1 / 11

页数：11

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