Complex SNP-related sequence variation in segmental genome duplications

David Fredman, Stefan White, Suzanna Potter, Evan Eichler, Johan den Dunnen, Anthony Brookes

Research output: Contribution to journalLetterOther

195 Citations (Scopus)


Evolution, Molecular Female Gene Dosage Genetic Markers Genetic Variation Genome, Human There is uncertainty about the true nature of predicted single-nucleotide polymorphisms (SNPs) in segmental duplications (duplicons) and whether these markers genuinely exist at increased density as indicated in public databases. We explored these issues by genotyping 157 predicted SNPs in duplicons and control regions in normal diploid genomes and fully homozygous complete hydatidiform moles. Our data identified many true SNPs in duplicon regions and few paralogous sequence variants. Twenty-eight percent of the polymorphic duplicon sequences we tested involved multisite variation, a new type of polymorphism representing the sum of the signals from many individual duplicon copies that vary in sequence content due to duplication, deletion or gene conversion. Multisite variations can masquerade as normal SNPs when genotyped. Given that duplicons comprise at least 5 of the genome and many are yet to be annotated in the genome draft, effective strategies to identify multisite variation must be established and deployed.
Original languageEnglish
Pages (from-to)861 - 866
Number of pages6
JournalNature Genetics
Issue number8
Publication statusPublished - 2004
Externally publishedYes

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