Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation

被引：339

作者：

Kerkel, Kristi ^{[1
]}

Spadola, Alexandra ^{[2
]}

Yuan, Eric ^{[1
]}

Kosek, Jolanta ^{[1
]}

Jiang, Le ^{[1
]}

Hod, Eldad ^{[3
]}

Li, Kerry ^{[1
]}

Murty, Vundavalli V. ^{[1
,3
]}

Schupf, Nicole ^{[4
,5
]}

Vilain, Eric ^{[6
,7
]}

Morris, Mitzi ^{[8
]}

Haghighi, Fatemeh ^{[8
]}

Tycko, Benjamin ^{[1
,3
]}

机构：

[1] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY 10032 USA

[2] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY 10032 USA

[3] Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA

[4] Columbia Univ, Med Ctr, Gertrude H Sergievsky Ctr, New York, NY 10032 USA

[5] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY 10032 USA

[6] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

[8] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 07期

关键词：

D O I：

10.1038/ng.174

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Allele-specific DNA methylation (ASM) is a hallmark of imprinted genes, but ASM in the larger nonimprinted fraction of the genome is less well characterized. Using methylation-sensitive SNP analysis (MSNP), we surveyed the human genome at 50K and 250K resolution, identifying ASM as recurrent genotype call conversions from heterozygosity to homozygosity when genomic DNAs were predigested with the methylation-sensitive restriction enzyme HpaII. Using independent assays, we confirmed ASM at 16 SNP-tagged loci distributed across various chromosomes. At 12 of these loci (75%), the ASM tracked strongly with the sequence of adjacent SNPs. Further analysis showed allele-specific mRNA expression at two loci from this methylation-based screen -the vanin and CYP2A6-CYP2A7 gene clusters -both implicated in traits of medical importance. This recurrent phenomenon of sequence-dependent ASM has practical implications for mapping and interpreting associations of noncoding SNPs and haplotypes with human phenotypes.

引用

页码：904 / 908

页数：5

共 23 条

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