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Large-Scale Zygosity Testing Using Single Nucleotide Polymorphisms

Published online by Cambridge University Press:  21 February 2012

Ulf Hannelius ,
Loreana Gherman ,
Ville-Veikko Mäkelä ,
Astrid Lindstedt ,
Marco Zucchelli ,
Camilla Lagerberg ,
Gunnel Tybring ,
Juha Kere  and
Cecilia M Lindgren
Ulf Hannelius*
Affiliation:
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. ulf.hannelius@biosci.ki.se
Loreana Gherman
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ville-Veikko Mäkelä
Affiliation:
Clinical Research Centre, Karolinska University Hospital, Stockholm, Sweden.
Astrid Lindstedt
Affiliation:
Clinical Research Centre, Karolinska University Hospital, Stockholm, Sweden.
Marco Zucchelli
Affiliation:
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Camilla Lagerberg
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Gunnel Tybring
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Juha Kere
Affiliation:
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; Clinical Research Centre, Karolinska University Hospital, Stockholm, Sweden; Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
Cecilia M Lindgren
Affiliation:
Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom.
*
*Address for correspondence: Ulf Hannelius, Department of Biosciences and Nutrition, Karolinska Institutet, Hälsovägen 7-9, 14157 Huddinge, Sweden

Abstract

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A requirement for performing robust genetic and statistical analyses on twins is correctly assigned zygosities. In order to increase the power to detect small risk factors of disease, zygosity testing should also be amenable for high throughput screening. In this study we validate and implement the use of a panel of 50 single nucleotide polymorphisms (SNPs) for reliable high throughput zygosity testing and compare it to a panel of 16 short tandem repeats (STRs). We genotyped both genomic (gDNA) and whole genome amplified DNA (WGA DNA), ending up with 47 SNP and 11 STR markers fulfilling our quality criteria. Out of 99 studied twin pairs, 2 were assigned a different zygosity using SNP and STR data as compared to self reported zygosity in a questionnaire. We also performed a sensitivity analysis based on simulated data where we evaluated the effects of genotyping error, shifts in allele frequencies and missing data on the qualitative zygosity assignments. The frequency of false positives was less than 0.01 when assuming a 1% genotyping error, a decrease of 10% of the observed minor allele frequency compared to the actual values and up to 10 missing markers. The SNP markers were also successfully genotyped on both gDNA and WGA DNA from whole blood, saliva and filter paper. In conclusion, we validate a robust panel of 47 highly multiplexed SNPs that provide reliable and high quality data on a range of different DNA templates.

Type
Articles
Information
Twin Research and Human Genetics , Volume 10 , Issue 4 , 01 August 2007 , pp. 604 - 625
Copyright
Copyright © Cambridge University Press 2007