The tetranucleotide repeat polymorphism D21S1245 demonstrates hypermutability in germline and somatic cells

• Published in: Human molecular genetics 1995-07, Vol.4 (7), p.1193-1199
• Main Authors: Talbot, C.Conover, Avramopouls, Dimitris, Gerken, Steven, Chakravarti, Aravinda, Armour, John A., Matsunami, Norisada, White, Ray, Antonarakis, Stylianos E.
• Format: Article
• Language: English
• Subjects: Alleles; Base Sequence; Biological and medical sciences; chromosome 21; Chromosome Mapping; Chromosomes, Human, Pair 21 - genetics; Classical genetics, quantitative genetics, hybrids; D21S1245 locus; Female; Fundamental and applied biological sciences. Psychology; Genetic Linkage; Genetic Markers; Genetics of eukaryotes. Biological and molecular evolution; Germ-Line Mutation; Human; Humans; Male; man; meiosis; Molecular Sequence Data; Polymorphism, Genetic - genetics; repeated sequence; Repetitive Sequences, Nucleic Acid; Sequence Analysis, DNA; tetranucleotide repeat
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/4.7.1193

Six novel polymorphic short sequence repeats were identified and localized on the linkage map of human chromosome 21 by genotyping the CEPH reference pedigrees. One of these markers, the tetrameric (AAAG)n repeat D21S1245, was found to be hypermutable. In the DNAs from lymphoblastoid cell lines of members of the 40 CEPH families a total of 18 new alleles were detected. These new alleles, sometimes appearing in mosaic forms, arose equally in paternal and maternal DNAs, and could be equally larger or smaller than the alleles from which they were derived. The larger alleles of D21S1245 are more prone to be converted to new alleles. None of the new alleles with mosaicism were present in the corresponding genomic blood DNA, and therefore originated during or after the establishment of the lymphoblastoid cell lines; half of the new alleles without mosaicism were also found in genomic blood DNA of the appropriate CEPH individuals. The range of germline mutation rate observed In the 716 meioses examined was 0.56–1.4×10−2 the range of somatic mutations observed in the 405 cell lines examined was 1.96–3.46×10−2 This is one of the most hypermutabie microsatellite repeat polymorphism in the human genome detected to date. D21S1245, is highly polymorphic (heterozygosity of 0.96) and maps between D21S231 and D21S198.