Studies of Restriction Fragments

The study of restriction fragment length polymorphisms is important to diagnosis. More than 80% of carriers can be detected, and antenatal diagnosis often is possible. Approximately one-third of the mothers of males and two-thirds of the mothers of females have been found to be noncarriers, reflecting the greater propensity for mutation in the male gamete. 

In the formation of the zygote, all mitochondria are contributed by the ovum. Therefore, mtDNA is transmitted by maternal inheritance in a vertical, nonmendelian fashion. Strictly maternal transmission of mtDNA has been documented in humans by studies of restriction fragment length polymorphisms (RFLPs) in DNA from platelets. As exemplified by the disorders outlined above,... 

The friction factor per base pair y for rotation of DNA around its symmetry axis was determined from FPA studies of restriction fragments containing N+ 1 =43 and 69 bp.(109) Both fragments are sufficiently short that a substantial amplitude of C (t), and also F (t), resides in their Uniform Mode Zones. Particular values of certain parameters were assumed, namely, the rise per base pair h = 3.4 A, the hydrodynamic radius b = 12 A for transverse motion in Eqs. (4.43)-(4.47) (which are quite insensitive to b), and D, = 1.8 x 106 s-1 for 43 bp and D = 4.8 x 105 s for 69 bp. The latter values were extrapolated or interpolated from the data of Elias and Eden using an inverse cubic relation between DL and L. They are close to the values calculated using the theory of Tirado and Garcia de la Torre.(129)... 

In many localities, newborn screening has become standard for this disorder, which in the general population has an approximate incidence of 1/250,000 live births. Carrier detection is possible, either by measurement of enzymatic activity in cultured fibroblasts or by study of restriction endonuclease fragments of DNA. Antenatal testing is also available. 

Specific mutations have been associated with specific haplotypes, the latter determined by analysis of restriction fragment length polymorphisms. This approach has been utilized for prenatal diagnosis. The study of haplotypes also has revealed that the majority (=75%) of northern European patients are compound PKU heterozygotes. 

A study of an extended family in Venezuela with Huntington s chorea demonstrated that family members with the disease show a distinct and characteristic pattern of restriction fragment lengths, leading to a new screening test. The same methods of investigation revealed patterns for cystic fibrosis, adult polycystic kidney disease, Due lien nc muscular dystrophy, and others. 

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