Summary
A novel procedure is presented to estimate the ratio of male to female mutation rates for Duchenne muscular dystrophy (DMD). X-specific restriction fragment length polymorphisms are used to establish DNA haplotypes in three-generation DMD families. From the proportion of DMD patients who have inherited their maternal grandfather's X chromosome, the ratio of mutation rates can be calculated. In contrast to classical methods, the proposed procedure is not restricted to sporadic or familiar cases nor is any information on the carrier status of female relatives required.
This is a preview of subscription content, log in via an institution to check access.
References
Bakker E, Hofker MH, Goor N, Mandel JL, Wrogemann K, Davies KE, Kunkel LM, Willard HF, Fenton WA, Sandkuyl L, Majoor-Krakauer D, van Essen AJ, Jahoda MGJ, Sachs ES, van Ommen GJB, Pearson PL (1985) Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLP's. Lancet I:655–658
Bucher K, Ioanescu V, Hanson J (1980) Frequency of new mutants among boys with Duchenne muscular dystrophy. Am J Med Genet 7:27–46
Camerino G, Grzeschik KH, Jaye M, de la Salle H, Tolstoshev P, Lecocq JP (1984) Regional localization on the human X chromosome and polymorphism of the coagulation factor IX gene (hemophilia B locus). Proc Nat Acad Sci USA 81:498–502
Caskey CT, Nussbaum RL, Cohan LC, Pollack L (1980) Sporadic occurrence of Duchenne muscular dystrophy: evidence for new mutation. Clin Genet 18:329–341
Crow JF, Denniston C (1985) Mutation in human populations. Adv Hum Genet 14:59–123
Danieli GA, Barbujani G (1984) Duchenne muscular dystrophy: frequency of sporadic cases. Hum Genet 67:252–256
Danieli GA, Mostacciuolo ML, Bonfante A, Angelini C (1977) Duchenne muscular dystrophy: a population study. Hum Genet 35:225–231
Davie AM, Emery AEH (1978) Estimation of proportion of new mutants among cases of Duchenne muscular dystrophy. J Med Genet 15:339–345
Francke U, Felsenstein J, Gartler SM, Migeon BR, Dancis J, Seegmiller JE, Bakay F, Nyhan WL (1976) The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease. Am J Hum Genet 28:123–137
Gardner-Medwin D (1970) Mutation rate in Duchenne type of muscular dystrophy. J Med Genet 7:334–337
Gitschier J, Wood WI, Govalka TM, Wion KK, Chen EY, Eaton DH, Vehar GA, Capon DJ, Lawn RM (1985) Characterisation of the human factor VIII gene. Nature 314:738–740
Goodfellow PN, Davies KE, Ropers HH (1985) Report of the committee on the genetic constitution of the X and Y chromosomes. Cytogenet Cell Genet 40:296–352
Haldane JBS (1935) The rate of spontaneous mutation of a human gene. J Genet 31:317–326
Harper PS, O'Brien T, Murray JM, Davies KE, Pearson PL, Williamson R (1983) The use of linked DNA polymorphisms for genotype prediction in families with Duchenne muscular dystrophy. J Med Genet 20:252–254
Moser H, Wiesmann U (1971) Serum-Creatin-Kinase und Sulfhydril-Konzentration nach ischämischer Arbeitsbelastung der Vorderarmmuskulatur bei Patienten und Konduktorinnen der progressiven Muskeldystrophic Duchenne. Klin Wochenschr 49:488–494
Moser H (1977) Heterozygotenerfassung und genetische Beratung bei der progressiven Muskeldystrophie Duchenne. Schweiz Rundsch Med Praxis 66:814–822
Nussbaum RL, Crowder WE, Nyhen WL, Caskey CT (1983) A three allele restriction fragment length polymorphism at the hypoxanthine-guanine phosphoribosyltransferase locus in man. Proc Natl Acad Sci USA 80:4035–4039
Pickard NA, Gruemer HD, Verrill HL, Isaacs ER, Robinow M, Nance WE, Myers EC, Goldsmith D (1978) Systemic membrane defect in the proximal muscular dystrophies. N Engl J Med 299: 841–846
Roses AD, Roses MJ, Miller SE, Hull KL, Appel SH (1976) Carrier detection in Duchenne muscular dystrophy. N Engl J Med 294: 193–198
Vogel F, Rathenberg R (1975) Spontaneous mutations in man. Adv Hum Genet 5:223–318
Winter RM (1985) The estimation of recurrence risks in monogenic disorders using flanking marker loci. J Med Genet 22:12–15
Yasuda N, Kondo K (1980) No sex difference in mutation rates of Duchenne muscular dystrophy. J Med Genet 17:106–111
Zatz M, Frota-Pessoa O, Levy JA, Peres CA (1976) Creatine phosphokinase (CPK) activity in relatives of patients with X-linked muscular dystrophies: a Brazilian study. J Genet Hum 24:153–168
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Müller, C.R., Grimm, T. Estimation of the male to female ratio of mutation rates from the segregation of X-chromosomal DNA haplotypes in Duchenne muscular dystrophy families. Hum Genet 74, 181–183 (1986). https://doi.org/10.1007/BF00282088
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00282088