Unstable trinucleotide repeats

Unstable trinucleotide repeats Multifactorial inheritance Mitochondrial inheritance... 

The answer is c. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 57-76. Wilson, pp 227-246.) Anticipation refers to the worsening of the symptoms of disease in succeeding generations. The lamous geneticist L.S. Penrose dismissed anticipation as an artifact, but the phenomenon has been validated by the discovery of expanding trinucleotide repeats. Stein-ert myotonic dystrophy is caused by unstable trinucleotide repeats near a... 

Trinucleotide sequences that increase in number (microsateUite instability) can cause disease. The unstable p(CGG) repeat sequence is associated with the fragile X syndrome. Other trinucleotide repeats that undergo dynamic mutation (usually an increase) are associated with Huntington s chorea (CAG), myotonic dystrophy (CTG), spinobulbar muscular atrophy (CAG), and Kennedy s disease (CAG). 

Huntington s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington s disease chromosomes. Cell 72 971-983,1993. 

Warner JP, Barron LH, Brock DJH. A new polymerase chain reaction (PCR) assay for the trinucleotide repeat that is unstable and expanded on Huntington s disease chromosomes. Molec Cellular Probes 1993 7 235-9. 

Ikeuchi, T., Koide, R., Tanaka, H. et al. Dentatorubral pallidoluysian atrophy clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat. Ann. Neurol. 37 769-775,1995. 

By 1986, it was noted that patients with a clinical onsetprior to age 20 had a preponderant inheritance from affected fathers (Harper, 1996 Fahn, 2005). In those patients with onset prior to 10 years, the incidence approaches 100% (Hayden, 1981). The CAG repeats were found to be unstable in gametes and with high repeat trinucleotide lengths (Riley and Lang, 1991 Duyao et al., 1993 Fahn, 2005). The instability in sperm DNA may explain the increased number of repeats in successive generations of male derived offspring— anticipation (Duyao... 

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