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Article: Pooled genotyping of microsatellite markers in parent-offspring trios

TitlePooled genotyping of microsatellite markers in parent-offspring trios
Authors
Issue Date2000
PublisherCold Spring Harbor Laboratory Press, Publications Department. The Journal's web site is located at http://www.genome.org
Citation
Genome Research, 2000, v. 10 n. 1, p. 105-115 How to Cite?
AbstractWe studied the extent to which genotyping of simple sequence repeat polymorphisms (SSRs) in pooled DNA samples can be used to predict differences in allele frequencies between parents and their affected offspring. We also developed a simple method of correction for the effects of stutter and differential amplification on the analysis of SSRs in pooled DNA samples based on widely available software. We genotyped individually eight polymorphic microsatellite markers in 110 parent-offspring trios affected with bipolar affective disorder (BP). Analysis of pooled DNA samples predicted very accurately the differences in individual allele frequency distributions between children and their parents. The mean error was < 1% [range 0%-3.2%] when marker-specific corrections for stutter and differential amplification were performed. We show that if an individual allele is significantly preferentially transmitted from parents to affected offspring, the difference in the frequency of that allele would be sufficiently large to be detected with pooling in most situations. We propose recommendations for disequilibrium mapping with pooling in which both case-control samples and trios are used in an initial screen and markers are genotyped individually only if they satisfy very relaxed criteria for statistical significance. The use of case-control samples should reduce the false-negative rate as the differences in allele frequencies between cases and controls are twice as high in the presence of the same genetic effect. The use of trios will confirm or reject any suggested differences, thus reducing the false-positive rate that can be created by hidden population stratification.
Persistent Identifierhttp://hdl.handle.net/10722/175818
ISSN
2015 Impact Factor: 11.351
2015 SCImago Journal Rankings: 14.352
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKirov, Gen_US
dc.contributor.authorWilliams, Nen_US
dc.contributor.authorSham, Pen_US
dc.contributor.authorCraddock, Nen_US
dc.contributor.authorOwen, MJen_US
dc.date.accessioned2012-11-26T09:01:33Z-
dc.date.available2012-11-26T09:01:33Z-
dc.date.issued2000en_US
dc.identifier.citationGenome Research, 2000, v. 10 n. 1, p. 105-115en_US
dc.identifier.issn1088-9051en_US
dc.identifier.urihttp://hdl.handle.net/10722/175818-
dc.description.abstractWe studied the extent to which genotyping of simple sequence repeat polymorphisms (SSRs) in pooled DNA samples can be used to predict differences in allele frequencies between parents and their affected offspring. We also developed a simple method of correction for the effects of stutter and differential amplification on the analysis of SSRs in pooled DNA samples based on widely available software. We genotyped individually eight polymorphic microsatellite markers in 110 parent-offspring trios affected with bipolar affective disorder (BP). Analysis of pooled DNA samples predicted very accurately the differences in individual allele frequency distributions between children and their parents. The mean error was < 1% [range 0%-3.2%] when marker-specific corrections for stutter and differential amplification were performed. We show that if an individual allele is significantly preferentially transmitted from parents to affected offspring, the difference in the frequency of that allele would be sufficiently large to be detected with pooling in most situations. We propose recommendations for disequilibrium mapping with pooling in which both case-control samples and trios are used in an initial screen and markers are genotyped individually only if they satisfy very relaxed criteria for statistical significance. The use of case-control samples should reduce the false-negative rate as the differences in allele frequencies between cases and controls are twice as high in the presence of the same genetic effect. The use of trios will confirm or reject any suggested differences, thus reducing the false-positive rate that can be created by hidden population stratification.en_US
dc.languageengen_US
dc.publisherCold Spring Harbor Laboratory Press, Publications Department. The Journal's web site is located at http://www.genome.orgen_US
dc.relation.ispartofGenome Researchen_US
dc.subject.meshBipolar Disorder - Geneticsen_US
dc.subject.meshCase-Control Studiesen_US
dc.subject.meshChilden_US
dc.subject.meshChromosomes, Human, Pair 4 - Geneticsen_US
dc.subject.meshDna - Analysisen_US
dc.subject.meshFalse Negative Reactionsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Frequencyen_US
dc.subject.meshGenotypeen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMicrosatellite Repeats - Geneticsen_US
dc.subject.meshParentsen_US
dc.subject.meshPolymorphism, Genetic - Geneticsen_US
dc.subject.meshSensitivity And Specificityen_US
dc.titlePooled genotyping of microsatellite markers in parent-offspring triosen_US
dc.typeArticleen_US
dc.identifier.emailSham, P: pcsham@hku.hken_US
dc.identifier.authoritySham, P=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid10645955-
dc.identifier.scopuseid_2-s2.0-0033954077en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033954077&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume10en_US
dc.identifier.issue1en_US
dc.identifier.spage105en_US
dc.identifier.epage115en_US
dc.identifier.isiWOS:000085344200012-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridKirov, G=26643478800en_US
dc.identifier.scopusauthoridWilliams, N=7402772034en_US
dc.identifier.scopusauthoridSham, P=34573429300en_US
dc.identifier.scopusauthoridCraddock, N=36487591300en_US
dc.identifier.scopusauthoridOwen, MJ=36044041500en_US

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