title: Complex SNP-related sequence variation in segmental genome duplications.
abstract: 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.
authors.affiliation: Center for Genomics and Bioinformatics, Karolinska Institute, Berzelius väg 35, S-171 77 Stockholm, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Fredman
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: White
authors.forename: Susanna
authors.initials: S
authors.lastname: Potter
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.forename: Johan T
authors.initials: JT
authors.lastname: Den Dunnen
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Brookes
mesh_terms: D019143:Evolution, Molecular; D005260:Female; D018628:Gene Dosage; D005819:Genetic Markers; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D005819:Genetic Markers