Disease-related mutations

The Task Force considered replication a necessary first step "before either linked markers or putative disease-related mutations are used as a basis of genetic tests" (Holtzman and Watson, 1998, p. 25). Reported associations between... 

Keywords Prion protein Molecular dynamics simulation Protein dynamics Protein misfolding pH-induced misfolding Disease-related mutations... 

In addition to conventional DNA, other variants can be used as probe DNA. In order to distinguish single-base mutations such as disease related mutations, having stronger hybridization is essential, and this can be achieved by using novel oligomers such as PNA and LNA. 

A distinct type of polymorphism was observed in the AP(l-40)-Iowa mutant D23N [44, 118]. In the same fibril preparation both parallel and antiparallel P-structures coexisted, the latter representing the major conformation. This finding illustrates that a single disease-related mutation can have extensive consequences for amyloid structure. 

Hattori, N., Yamamoto, M., Yoshihara, T. et al. Study Group for Hereditary Neuropathy in Japan. Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32) a clinicopathological study of 205 Japanese patients. Brain 126 134-151,2003. 

Shigeno K, Yoshida H, Pan L, Luo JM, Fujisawa S, Naito K, Nakamura S, Shinjo K, Takeshita A, Ohno R, Ohnishi K (2004) Disease-related potential of mutations in transcriptional cofactors CREB-binding protein and p300 in leukemias. Cancer Lett. 213 11—20 Shiio Y, Eisenman RN (2003) Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci U S A 100 13225-13230... 

The other two diseases related to UGT1A1 are Crigler-Najjar (CN) syndrome types I and II. Many different mutations in UGT1A1 have been identified. CN type I patients express a mutated protein that is essentially devoid of activity. These patients therefore are unable to conjugate bilirubin. Until recently, this condition was lethal in childhood however, now these patients can be treated with phototherapy (discussed in the next section on Photobilirubin) and liver transplantation. Patients with CN type II express a mutated protein that retains some activity. These patients generally respond to phenobarbital, which increases the transcription of UGT1A1. Both CN types I and II are recessive disorders and rare. 

Intestinal absorption of copper is mediated by coppertransporting P-type ATPase 7A (ATP7A) or Menkes disease protein. Mutations in the ATP7A gene lead to Menkes disease in humans that is characterized by congenital impairment in intestinal transport of copper see Metal-related Diseases of Genetic Origin) ... 

A. Diseases related to abnormal hemoglobin Sickle cell anemia results from a point mutation (GAG to GTG) that causes valine to replace glutamate at position 6 in the P-globin chain. In hemoglobin Wayne, deletion of a base causes a frameshift that produces the wrong sequence of amino acids in the chain beyond position 127. 

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