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1.  DNA methylation profiling of human chromosomes 6, 20 and 22 
Nature genetics  2006;38(12):1378-1385.
DNA methylation constitutes the most stable type of epigenetic modifications modulating the transcriptional plasticity of mammalian genomes. Using bisulfite DNA sequencing, we report high-resolution methylation reference profiles of human chromosomes 6, 20 and 22, providing a resource of about 1.9 million CpG methylation values derived from 12 different tissues. Analysis of 6 annotation categories, revealed evolutionary conserved regions to be the predominant sites for differential DNA methylation and a core region surrounding the transcriptional start site as informative surrogate for promoter methylation. We find 17% of the 873 analyzed genes differentially methylated in their 5′-untranslated regions (5′-UTR) and about one third of the differentially methylated 5′-UTRs to be inversely correlated with transcription. While our study was controlled for factors reported to affect DNA methylation such as sex and age, we did not find any significant attributable effects. Our data suggest DNA methylation to be ontogenetically more stable than previously thought.
PMCID: PMC3082778  PMID: 17072317
2.  A high resolution HLA and SNP haplotype map for disease association studies in the extended human MHC 
Nature genetics  2006;38(10):1166-1172.
The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and play an essential role in self/non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune disease1. Yet identification of causal variants is problematic due to linkage disequilibrium (LD) that extends across multiple HLA and non-HLA genes in the MHC2,3. We therefore set out to characterize the LD patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common single nucleotide polymorphisms (SNPs) and deletion/insertion polymorphisms (DIPs) across four population samples. The analysis provides informative tag SNPs that capture some of the variation in the MHC region and that could be used in initial disease association studies, and provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.
PMCID: PMC2670196  PMID: 16998491
3.  The rates of de novo meiotic deletions and duplications causing several genomic disorders in the male germline 
Nature genetics  2007;40(1):90-95.
Meiotic recombination between highly-similar duplicated sequences (non-allelic homologous recombination, NAHR) generates deletions, duplications, inversions, and translocations, and is responsible for genetic diseases known as ‘genomic disorders’, most of which are caused by altered copy number of dosage sensitive genes. NAHR Hotspots have been identified within some duplicated sequences. We have developed sperm-based assays to measure the de novo rate of reciprocal deletions and duplications at 4 NAHR hotspots. We used these assays to dissect the relative rates of NAHR between different pairs of duplicated sequences. We show that: (i) these NAHR hotspots are specific to meiosis, (ii) deletions are generated at a higher rate than their reciprocal duplications in the male germline and (iii) some of these genomic disorders are likely to have been under-ascertained clinically, most notably the duplication of 7q11, the reciprocal of the Williams-Beuren Syndrome deletion.
PMCID: PMC2669897  PMID: 18059269

Results 1-3 (3)