Blood Ties: Chimerism Can Mask Twin Discordance in High-Throughput Sequencing
Twin studies have long provided a means to separate the contributions of genetic and environmental factors. A recent pioneering report by Baranzini et al. presented an analysis of the complete genomes and epigenomes of a monozygotic (MZ) twin pair discordant for multiple sclerosis. This failed to fi...
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Published in | Twin research and human genetics Vol. 14; no. 2; pp. 137 - 143 |
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Main Author | |
Format | Journal Article |
Language | English |
Published |
Cambridge, UK
Cambridge University Press
01.04.2011
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Subjects | |
Online Access | Get full text |
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Summary: | Twin studies have long provided a means to separate the contributions of genetic and environmental factors. A recent pioneering report by Baranzini et al. presented an analysis of the complete genomes and epigenomes of a monozygotic (MZ) twin pair discordant for multiple sclerosis. This failed to find any difference between the twins, raising doubts regarding the value of whole-genome twin studies for defining disease susceptibility alleles. However, the study was carried out with DNA extracted from blood. In many cases, the hematopoietic lineages of MZ twins are chimeric due to twin-to-twin exchange of hematopoietic stem cells during embryogenesis. We therefore wondered how chimerism might impact the ability to identify genetic differences. We inferred the blood chimerism rates and profiles of more than 30 discordant twin cases from a wide variety of medical conditions. We found that the genotype compositions of the twins were highly similar. We then benchmarked the performance of SNP callers to detect discordant variations using high-throughput sequencing data. Our analysis revealed that chimerism patterns, well within the range normally observed in MZ twins, greatly reduce the sensitivity of SNP calls. This raises questions regarding any conclusions of genomic homogeneity that might be drawn from studies of blood-derived twin DNA. |
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Bibliography: | istex:6E57D9039D1B1C5925EE3E0F41BEB034EC21A8A4 PII:S1832427400011269 ark:/67375/6GQ-3FFH69PX-9 ADDRESS FOR CORRESPONDENCE: Yaniv Erlich, Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, United States of America. ArticleID:01126 Twin Research and Human Genetics, Vol. 14, No. 2, 2011: 137-143 TRHG_c.jpg ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1832-4274 1839-2628 |
DOI: | 10.1375/twin.14.2.137 |