Estimation of the male to female ratio of mutation rates from the segregation of X-chromosomal DNA haplotypes in Duchenne muscular dystrophy families

Abstract

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.

Molecular Analyses in Families with Hunter Syndrome Indicate Unequal Male and Female Mutation Rates in the Iduronate-2-Sulfatase Gene

“…Figure 1) and transmitted cases with heterozygous mother inherited the mutation from heterozygous grandmother or from de novo germline mutation of a grandparent (Type T, Figure 1) [32]. The proportion of sporadic cases and transmitted cases is determined by mutation rates μ and ν for female and male germ cells, respectively.…”

“…The proportion of type S and type T and the probability of maternal grandfather germline mutation are a function of ν/μ ratio. (ν, male mutation rate, μ, female mutation rate, adapted from Refs [31,32]).…”

“…The sporadic cases and the transmitted cases with mutations occurred from MGF represent indirect observation of de novo maternal (female) and grand-paternal (male) germline mutations, respectively. Since the probability of sporadic cases and transmitted MGF cases is a function of the ν/μ ratio (Figure 1), methods for estimation of the ν/μ ratio through detection of sporadic cases and transmitted MGF cases have been proposed [32][33][34]. Knowing the proportion (s) of mothers being a mutation non-carrier, the male-to-female ratio of mutation rates (k=ν/ μ) could be calculated using a formula s=1/(2+k), while knowing the probability of transmitted MGF can also infer k value using Pmgf=k/ (4+2k).…”

“…Knowing the proportion (s) of mothers being a mutation non-carrier, the male-to-female ratio of mutation rates (k=ν/ μ) could be calculated using a formula s=1/(2+k), while knowing the probability of transmitted MGF can also infer k value using Pmgf=k/ (4+2k). It is estimated that about 120 families need to be studied in order to discriminate at the 95% significance level the hypothesis of ν=μ from a hypothesis of ν ≥ 5μ [32].…”

Minisatellite DNA Profiles: Rapid Sample Identification in Linkage Analysis

“…The linkage analysis technique is now widely used for research as well as diagno sis in inherited disorders such as cystic fi brosis and Duchenne muscular dystrophy [Harris et al, 1988;Muller and Grimm, 1986]. Correct identity of the DNA sam ples used is crucial for the accuracy of the method.…”