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Targeted DNA Methylation Analysis by Next-generation Sequencing
Published on: February 24, 2015
Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation
Kristi Kerkel1, Alexandra Spadola, Eric Yuan
1Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA.
Nature Genetics
|June 24, 2008
Summary
Allele-specific DNA methylation (ASM) is common in nonimprinted genes. This study found ASM frequently tracks with single nucleotide polymorphisms (SNPs), impacting genetic association studies.
Area of Science:
- Genomics
- Epigenetics
- Human Genetics
Background:
- Allele-specific DNA methylation (ASM) is characteristic of imprinted genes.
- ASM in the majority of nonimprinted human genome regions is not well understood.
- Understanding ASM is crucial for interpreting genetic variations and their phenotypic effects.
Purpose of the Study:
- To investigate the prevalence and characteristics of allele-specific DNA methylation in the nonimprinted human genome.
- To develop and apply a high-throughput method for identifying ASM across the genome.
- To explore the relationship between ASM and genetic variation, including single nucleotide polymorphisms (SNPs).
Main Methods:
- Utilized methylation-sensitive SNP analysis (MSNP) at 50K and 250K resolutions.
- Employed the methylation-sensitive restriction enzyme HpaII for DNA digestion.
- Confirmed identified ASM loci using independent experimental assays.
Main Results:
- Identified recurrent ASM through genotype call conversions from heterozygosity to homozygosity.
- Confirmed ASM at 16 SNP-tagged loci across diverse chromosomes.
- Observed that 75% of confirmed ASM loci showed strong correlation with adjacent SNP sequences.
- Detected allele-specific mRNA expression at two loci (vanin and CYP2A6-CYP2A7 gene clusters) linked to medical traits.
Conclusions:
- Sequence-dependent allele-specific DNA methylation is a recurrent phenomenon in the human genome.
- ASM has significant implications for the mapping and interpretation of noncoding SNP and haplotype associations with human phenotypes.
- This finding provides a new perspective on the functional relevance of genetic variation and epigenetic modifications.
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