Skip to main content Accessibility help
×
Home

Twins, Tissue, and Time: An Assessment of SNPs and CNVs

  • Paul Scheet (a1), Erik A. Ehli (a2) (a3), Xiangjun Xiao (a1), Catharina E. M. van Beijsterveldt (a4), Abdel Abdellaoui (a4), Robert R. Althoff (a5), Jouke Jan Hottenga (a4), Gonneke Willemsen (a4), Kelly A. Nelson (a2), Patricia E. Huizenga (a2), Yueshan Hu (a2) (a3), Christopher I. Amos (a6), Meike Bartels (a4), Maria M Groen-Blokhuis (a4), Eco JC de Geus (a4), James J. Hudziak (a5), Gareth E. Davies (a2) (a3) and Dorret I. Boomsma (a4)...

Abstract

With the desire to assess genetic variation across the lifespan in large-scale collaborative projects, one question is whether inference of copy number (CN) is sensitive to the source of material for deoxyribonucleic acid (DNA) analysis (e.g., blood and buccal) and another question is whether CN is stable as individuals age. Here, we address these questions by applying Affymetrix 6.0 single nucleotide polymorphism (SNP) micro-arrays to 1,472 DNA samples from 710 individuals from the Netherlands Twin Register, including twin and non-twin individuals (372 with buccal and blood derived DNA and 388 with longitudinal data). Similar concordance for CN and genotype inference between samples from the same individual [or from the monozygotic (MZ) co-twins] was found for blood and buccal tissues. There was a small but statistically significant decrease in across-tissue concordance compared with concordance of samples from the same tissue type. No temporal effect was seen on CN variation from the 388 individuals sampled at two time points ranging from 1 to 12 years apart. The majority of our individuals were sampled at age younger than 20 years. Genotype concordance was very high (R2 > 99%) between co-twins from 43 MZ pairs. For 75 dizygotic (DZ) pairs, R2 was ≈65%. CN estimates were highly consistent between co-twins from MZ pairs for both deletions (R2 ≈ 90%) and duplications (R2 ≈ 86%). For DZ, these were similar for within-individual comparisons, but naturally lower between co-twins (R2 ≈ 50–60%). These results suggest that DNA from buccal samples perform as well as DNA from blood samples on the current generation of micro-array technologies.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Twins, Tissue, and Time: An Assessment of SNPs and CNVs
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Twins, Tissue, and Time: An Assessment of SNPs and CNVs
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Twins, Tissue, and Time: An Assessment of SNPs and CNVs
      Available formats
      ×

Copyright

Corresponding author

address for correspondence: Paul Scheet, University of Texas MD Anderson Cancer Center, Department of Epidemiology, Unit 1340, 1155 Pressler, Houston, TX 77030. E-mail: pscheet@alum.wustl.edu

References

Hide All
Bartels, M., van Beijsterveldt, C. E., Derks, E. M., Stroet, T. M., Polderman, T. J., Hudziak, J. J., & Boomsma, D. I. (2007). Young Netherlands Twin Register (Y-NTR): A longitudinal multiple informant study of problem behavior. Twin Research and Human Genetics, 10, 311.
Boomsma, D. I., de Geus, E. J., Vink, J. M., Stubbe, J. H., Distel, M. A., Hottenga, J. J., Posthuma, D., van Beijsterveldt, T. C., Hudziak, J. J., Bartels, M., & Willemsen, G. (2006). Netherlands Twin Register: From twins to twin families. Twin Research and Human Genetics, 9, 849857.
Boomsma, D. I., Willemsen, G., Sullivan, P. F., Heutink, P., Meijer, P., Sondervan, D., Kluft, C., Smit, G., Nolen, W. A., Zitman, F. G., Smit, J. H., Hoogendijk, W. J., van Dyck, R., de Geus, E. J., & Penninx, B. W. (2008). Genome-wide association of major depression: Description of samples for the GAIN Major Depressive Disorder Study: NTR and NESDA biobank projects. European Journal of Human Genetics, 16, 335342.
Dellinger, A. E., Saw, S. M., Goh, L. K., Seielstad, M., Young, T. L., & Li, Y. J. (2010). Comparative analyses of seven algorithms for copy number variant identification from single nucleotide polymorphism arrays. Nucleic Acids Research, 38, e105.
Dlugos, D. J., Scattergood, T. M., Ferraro, T. N., Berrettinni, W. H., & Buono, R. J. (2005). Recruitment rates and fear of phlebotomy in pediatric patients in a genetic study of epilepsy. Epilepsy & Behavior, 6, 444446.
Ehli, E. A., Abdellaoui, A., Hu, Y., Hottenga, J. J., Kattenberg, M., van Beijsterveldt, T., Bartels, M., Althoff, R. R., Xiao, X., Scheet, P., de Geus, E. J., Hudziak, J. J., Boomsma, D. I., & Davies, G. E. (2012). De novo and inherited CNVs in MZ twin pairs selected for discordance and concordance on Attention Problems [published online ahead of print]. European Journal of Human Genetics, 20, 10371043.
Erlich, Y. (2011). Blood ties: Chimerism can mask twin discordance in high-throughput sequencing. Twin Research and Human Genetics, 14, 137143.
Estourgie-van Burk, G. F., Bartels, M., Boomsma, D. I., & Delemarre-van de Waal, H. A. (2010). Body size of twins compared with siblings and the general population: From birth to late adolescence. The Journal of Pediatrics, 156 (4), 586591.
Forsberg, L. A., Rasi, C., Razzaghian, H. R., Pakalapati, G., Waite, L., Thilbeault, K. S., Ronowicz, A., Wineinger, N. E., Tiwari, H. K., Boomsma, D., Westerman, M. P., Harris, J. R., Lyle, R., Essand, M., Eriksson, F, Assimes, T. L., Iribarren, C., Strachan, E., O'Hanlon, T. P., Rider, L. G., Miller, F. W., Giedraitis, V., Lannfelt, L., Ingelsson, M., Piotrowski, A., Pedersen, N. L., Absher, D., & Dumanski, J. P. (2012). Age-related somatic structural changes in the nuclear genome of human blood cells. American Journal of Human Genetics, 90, 217288.
Huang, L., Li, Y., Singleton, A. B., Hardy, J. A., Abecasis, G., Rosenberg, N. A., & Scheet, P. (2009). Genotype-imputation accuracy across worldwide human populations. The American Journal of Human Genetics, 84, 235250.
Korn, J. M., Kuruvilla, F. G., McCarroll, S. A., Wysoker, A., Nemesh, J., Cawley, S., Hubbell, E., Veitch, J., Collins, P. J., Darvishi, K., Lee, C., Nizzari, M. M., Gabriel, S. B., Purcell, S., Daly, M. J., & Altshuler, D. (2008). Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs. Nature Genetics, 40, 12531260.
Laurie, C. C., Laurie, C. A., Rice, K., Doheny, K. F., Zelnick, L. R., McHugh, C. P., Ling, H., Hetrick, K. N., Pugh, E. W., Amos, C., Wei, Q., Wang, L. E., Lee, J. E., Barnes, K. C., Hansel, N. N., Mathias, R., Daley, D., Beaty, T. H., Scott, A. F., Ruczinski, I., Scharpf, R. B., Bierut, L. J., Hartz, S. M., Landi, M. T., Freedman, N. D., Goldin, L. R., Ginsburg, D., Li, J., Desch, K. C., Strom, S. S., Blot, W. J., Signorello, L. B., Ingles, S. A., Chanock, S. J., Berndt, S. I., Le Marchand, L., Henderson, B. E., Monroe, K. R., Heit, J. A., de Andrade, M., Armasu, S. M., Regnier, C., Lowe, W. L., Hayes, M. G., Marazita, M. L., Feingold, E., Murray, J. C., Melbye, M., Feenstra, B., Kang, J. H., Wiggs, J. L., Jarvik, G. P., McDavid, A. N., Seshan, V. E., Mirel, D. B., Crenshaw, A., Sharopova, N., Wise, A., Shen, J., Crosslin, D. R., Levine, D. M., Zheng, X., Udren, J. I., Bennett, S., Nelson, S. C., Gogarten, S. M., Conomos, M. P., Heagerty, P., Manolio, T., Pasquale, L. R., Haiman, C. A., Caporaso, N., & Weir, B. S. (2012). Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nature Genetics, 44, 642650.
Meulenbelt, I., Droog, S., Trommelen, G., Boomsma, D., & Slagboom, P. (1995). High-yield noninvasive human genomic DNA isolation method for genetic studies in geographically dispersed families and populations. American Journal of Human Genetics, 57, 12521254.
Min, J. L., Lakenberg, N., Bakker-Verweij, M., Suchiman, E., Boomsma, D. I., Slagboom, P. E., & Meulenbelt, I. (2006). High microsatellite and SNP genotyping success rates established in a large number of genomic DNA samples extracted from mouth swabs and genotypes. Twin Research and Human Genetics, 9, 501506
Pinto, D., Darvishi, K., Shi, X., Rajan, D., Rigler, D., Fitzgerald, T., Lionel, A. C., Thiruvahindrapuram, B., Macdonald, J. R., Mills, R., Prasad, A., Noonan, K., Gribble, S., Prigmore, E., Donahoe, P. K., Smith, R. S., Park, J. H., Hurles, M. E., Carter, N. P., Lee, C., Scherer, S. W., & Feuk, L. (2011). Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants. Nature Biotechnology, 29, 512520.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D., Maller, J., Sklar, P., de Bakker, P. I., Daly, M. J., & Sham, P. C. (2007). PLINK: A tool set for whole-genome association and population-based linkage analyses. The American Journal of Human Genetics, 81, 559575.
Rincon, G., Tengvall, K., Belanger, J. M., Lagoutte, L., Medrano, J. F., André, C., Thomas, A., Lawley, C. T., Hansen, M. S., Lindblad-Toh, K., & Oberbauer, A. M. (2011). Comparison of buccal and blood-derived canine DNA, either native or whole genome amplified, for array-based genome-wide association studies. BMC Research Notes, 4, 226.
Talens, R. P., Boomsma, D. I., Tobi, E. W., Kremer, D., Jukema, J. W., Willemsen, G., Putter, H., Slagboom, P. E., & Heijmans, B. T. (2010). Variation, patterns, and temporal stability of DNA methylation: Considerations for epigenetic epidemiology. The FASEB Journal, 24, 3135.
van Dijk, B. A., Boomsma, D. I., & de Man, A. J. M. (1996). Blood group chimerism in human multiple births is not rare. American Journal of Medical Genetics, 61, 264268.
Willemsen, G., de Geus, E. J., Bartels, M., van Beijsterveldt, C. E., Brooks, A. I., Estourgie-van Burk, G. F., Fugman, D. A., Hoekstra, C., Hottenga, J. J., Kluft, K., Meijer, P., Montgomery, G. W., Rizzu, P., Sondervan, D., Smit, A. B., Spijker, S., Suchiman, H. E., Tischfield, J. A., Lehner, T., Slagboom, P. E., & Boomsma, D. I. (2010). The Netherlands Twin Register Biobank: A resource for genetic epidemiological studies. Twin Research and Human Genetics, 13, 231245.
Wang, K., Li, M., Hadley, D., Liu, R., Glessner, J., Grant, S. F., Hakonarson, H., & Bucan, M. (2007). PennCNV: An integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Research, 17, 16651674.
Woo, J. G., Sun, G., Haverbusch, M., Indugula, S., Martin, L. J., Broderick, J. P., Deka, R., & Woo, D. (2007). Quality assessment of buccal versus blood genomic DNA using the Affymetrix 500 K GeneChip. BMC Genetics, 8, 79.

Keywords

Related content

Powered by UNSILO
Type Description Title
PDF
Supplementary materials

Scheet Supplementary Material
Appendix

 PDF (283 KB)
283 KB

Twins, Tissue, and Time: An Assessment of SNPs and CNVs

  • Paul Scheet (a1), Erik A. Ehli (a2) (a3), Xiangjun Xiao (a1), Catharina E. M. van Beijsterveldt (a4), Abdel Abdellaoui (a4), Robert R. Althoff (a5), Jouke Jan Hottenga (a4), Gonneke Willemsen (a4), Kelly A. Nelson (a2), Patricia E. Huizenga (a2), Yueshan Hu (a2) (a3), Christopher I. Amos (a6), Meike Bartels (a4), Maria M Groen-Blokhuis (a4), Eco JC de Geus (a4), James J. Hudziak (a5), Gareth E. Davies (a2) (a3) and Dorret I. Boomsma (a4)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.