Blood ties: chimerism can mask twin discordance in high-throughput sequencing

Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies
Yaniv Erlich

Abstract

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 ...Continue Reading

References

Nov 1, 1991·American Journal of Medical Genetics·A FujimotoK Battersby
Oct 1, 1991·American Journal of Medical Genetics·P B KaplowitzJ E Spence
Feb 1, 1985·Journal of Medical Genetics·B DallapiccolaM Purpura
Jul 1, 1972·Acta paediatrica Scandinavica·A M Potter, L S Taitz
Jun 1, 1966·Journal of Medical Genetics·J H EdwardsJ Kahn
Feb 1, 1982·American Journal of Medical Genetics·J G RogersH Gold
Dec 1, 1982·American Journal of Medical Genetics·E WeissI M Rosenthal
Jan 1, 1980·Acta Obstetricia Et Gynecologica Scandinavica·I K PedersenJ Starup
Dec 17, 1997·Nature Genetics·N MartinG Machin
Jul 31, 1998·American Journal of Human Genetics·J MonteiroP K Gregersen
Jul 7, 2001·Early Human Development·P Gringras, W Chen
May 23, 2002·Human Molecular Genetics·Rosanna WeksbergJeremy Squire
Jun 7, 2003·Blood·Mel F GreavesAnthony M Ford
Jul 11, 2003·The New England Journal of Medicine·Vivienne L SouterIan A Glass
Sep 6, 2003·Lancet·Judith G Hall
Jan 7, 2004·American Journal of Medical Genetics. Part a·D Marcus-SoekarmanJ Engelen
Mar 25, 2004·American Journal of Medical Genetics. Part a·T R RohrerH G Doerr
Aug 21, 2004·Human Reproduction Update·Kirby L Johnson, Diana W Bianchi
Oct 30, 2004·The Journal of Trauma·Garth H UtterMichael P Busch
Apr 16, 2005·American Journal of Medical Genetics. Part a·Sylvie BourthoumieuFrançoise Esclaire
Nov 5, 2005·Human Reproduction·Rika AokiSadahiko Iwamoto
Feb 14, 2006·American Journal of Medical Genetics. Part a·Sylvie BourthoumieuCatherine Yardin
Oct 29, 2008·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·C K EkelundA Tabor
Jan 20, 2009·Nature Genetics·Zachary A KaminskyArt Petronis
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
Apr 14, 2009·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Geoffrey Machin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jun 11, 2009·European Journal of Human Genetics : EJHG·Jet BliekMarcel M A M Mannens
Dec 10, 2009·Nature Reviews. Genetics·Michael L Metzker
Dec 29, 2009·American Journal of Human Genetics·Simon EdvardsonOrly Elpeleg
Feb 27, 2010·American Journal of Medical Genetics. Part a·Lee KaplanJames F Gusella

❮ Previous
Next ❯

Citations

Oct 2, 2012·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Paul ScheetDorret I Boomsma
Aug 1, 2012·Nature Reviews. Genetics·Jenny van DongenDorret I Boomsma
Jun 10, 2014·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Marketa VlckovaZdenek Sedlacek
May 25, 2013·American Journal of Medical Genetics. Part a·Kristen ChenLinda Randolph
Dec 20, 2011·Journal of Autoimmunity·Dimitrios P BogdanosM Eric Gershwin
Dec 20, 2012·The Behavioral and Brain Sciences·Evan Charney
Dec 2, 2017·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Yuejuan XuRang Xu
Jan 9, 2018·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Sofia StamouliSven Bölte
Dec 16, 2020·Molecular Genetics & Genomic Medicine·Małgorzata RydzaniczRafał Płoski
Dec 6, 2020·Journal of Cardiovascular Development and Disease·Marcel GrunertSilke R Sperling

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

© 2021 Meta ULC. All rights reserved