The pattern of spontaneous germ-line mutation

relative rates of mutation at or near CpG dinucleotides in the factor IX gene

Cynthia D K Bottema, Rhett P. Ketterling, Erica Vielhaber, Hong Sup Yoon, Bobbie Gostout, David P. Jacobson, Amy Shapiro, Steve S. Sommer

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Mutations at CpG dinucleotides were delineated in the factor IX gene of 38 hemophilia B patients. When transitions at CpG were considered with those previously reported by us and those compiled in the factor IX mutation database, the following patterns emerged. Many CpG sites were mutated with high frequency, while two CpG sites were infrequently mutated (R29→Q and R116→ TGA). Of the 6 possible nonsense mutations and the 14 missense mutations that would produce a nonconservative change at conserved amino acids, all have been observed to cause hemophilia B except A-10→T and R338→Q. By contrast, none of the 6 missense changes at nonconserved amino acids have been observed to cause hemophilia B. At those CpG sites that are frequently mutated, the rate of transitions is estimated to be 20-fold higher than transitions at non-CpG sites. Point mutations in close proximity to CpG dinucleotides did not seem elevated.

Original languageEnglish (US)
Pages (from-to)496-503
Number of pages8
JournalHuman Genetics
Volume91
Issue number5
DOIs
StatePublished - Jun 1993

Fingerprint

Hemophilia B
Factor IX
Germ-Line Mutation
Mutation Rate
Mutation
Genes
Amino Acids
Nonsense Codon
Missense Mutation
Point Mutation
Databases

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Bottema, C. D. K., Ketterling, R. P., Vielhaber, E., Yoon, H. S., Gostout, B., Jacobson, D. P., ... Sommer, S. S. (1993). The pattern of spontaneous germ-line mutation: relative rates of mutation at or near CpG dinucleotides in the factor IX gene. Human Genetics, 91(5), 496-503. https://doi.org/10.1007/BF00217779

The pattern of spontaneous germ-line mutation : relative rates of mutation at or near CpG dinucleotides in the factor IX gene. / Bottema, Cynthia D K; Ketterling, Rhett P.; Vielhaber, Erica; Yoon, Hong Sup; Gostout, Bobbie; Jacobson, David P.; Shapiro, Amy; Sommer, Steve S.

In: Human Genetics, Vol. 91, No. 5, 06.1993, p. 496-503.

Research output: Contribution to journalArticle

Bottema, CDK, Ketterling, RP, Vielhaber, E, Yoon, HS, Gostout, B, Jacobson, DP, Shapiro, A & Sommer, SS 1993, 'The pattern of spontaneous germ-line mutation: relative rates of mutation at or near CpG dinucleotides in the factor IX gene', Human Genetics, vol. 91, no. 5, pp. 496-503. https://doi.org/10.1007/BF00217779
Bottema, Cynthia D K ; Ketterling, Rhett P. ; Vielhaber, Erica ; Yoon, Hong Sup ; Gostout, Bobbie ; Jacobson, David P. ; Shapiro, Amy ; Sommer, Steve S. / The pattern of spontaneous germ-line mutation : relative rates of mutation at or near CpG dinucleotides in the factor IX gene. In: Human Genetics. 1993 ; Vol. 91, No. 5. pp. 496-503.
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