Autosomal factor

Resistance genes can be dominant, recessive, incompletely dominant, or incompletely recessive. Resistance to carbamates and organophosphates is usually dominant or incompletely dominant. Resistance to DDT, Bt, and spinosyns is usually recessive. Resistance to dieldrin is usually incompletely dominant. Resistance to pyrethroids is usually incompletely recessive. As shown in Figure 10.1 and 10.2, diamondback moth resistance to per-methrin was inherited as an incompletely recessive, autosomal factor, whereas resistance to methomyl was inherited as an incompletely dominant, autosomal factor. In cases of monofactorial inheritance of resistance to insecticides, the degree of dominance (D) in the progeny can be calculated, as described by Stone (1968), as follows ... 

Nei M, Maruyama T, Wu C-I (1983) Models of evolution of reproductive isolation. Genetics 103 557-579 Pantazidis AC, Zouros E (1988) Location of an autosomal factor causing sterility in Drosophila moiavensis males carrying the Drosophila arizonensis Y chromosome. Heredity 60 299-304... 

Hereditary deficiency of Factor V is a rare autosomal recessive disorder. Combined deficiencies of Factors V and VIII have been identified in several families. 

Deficiency of Factor VII is relatively rare and inherited as an autosomal recessive disorder. Deficiency of Factor VII has been reported to be associated with bond abnormal bleeding and thrombotic tendencies. Deep vein thrombosis and pulmonary emboli have been reported in affected individuals. There is a very high frequency of Factor VII deficiency in people with the Dubin-Johnson syndrome, which is a congenital disorder of Hver function. 

Deficiency of the VIIFC portion of the Factor VIII complex results in classic hemophilia or hemophilia A and is inherited as a sex-linked recessive disorder. Based on the degree of deficiency of the VIIFC molecule three different forms of hemophilia A are recognized. Less than 1% VIIFC activity equals severe hemophilia A. Two to 10% of normal VIIFC activity equals moderately severe hemophilia A. Ten to 25% of normal VIIFC activity equals minimal symptomatic disease. Deficiency of the VIIFvWFAg portion of the Factor VIII complex results in von WiUebrand disease. There are at present five principal types of von WiUebrand disease and numerous subtypes or variants. For the most part, von WiUebrand disease is inherited as an autosomal dominant, and a few subtypes may be inherited as an autosomal recessive trait. 

Congenital deficiency of Factor XI is a relatively rare coagulopathy that has been reported as both an autosomal dominant and autosomal recessive trait. This deficiency state occurs predominantly in the Jewish population. Most patients with this deficiency state remain asymptomatic until trauma or surgery is encountered. Spontaneous hemorrhage is rare in this population. 

Congenital deficiency of Factor XII is inherited as an autosomal recessive trait. Deficiency of this factor is rarely associated with any coagulopathy. It has been observed that people deficient in this factor may have an increased frequency of thromboembolic compHcations. 

Congenital deficiency of Factor Xlll is inherited as an autosomal recessive trait and is frequendy recognized at birth because of delayed persistent hemorrhage from the umbiUcus. In Factor Xlll-deficient people wound healing is defective and wound dehiscence is common. 

Von Willebrand disease (vWD) is the most common inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor. The disease prevalence is estimated at 30 to 100 cases per million. In contrast to hemophilia, vWD is inherited as an autosomal dominant disorder (although autosomal recessive cases exist), ensuing equal frequency in male and females.16... 

Type 2 vWD deficiency of vWF and factor VIII Qualitative abnormalities of vWF 10%-30% Autosomal dominant... 

A 2B 2M 2N Type 3 vWD Decreased platelet-dependent vWF function owing to lack of larger multime rs Increased platelet-dependent vWF function owing to lack of larger multime rs Defective platelet-dependent vWF functions not associated with multimer defects Defective vWF binding to factor VIII Severe quantitative deficiency of vWF 1 %-5% Autosomal recessive... 

Ying L, Katz Y, Schlesinger M et al. Complement factor H gene mutation associated with autosomal recessive-atypical hemolytic uremic syndrome. Am J Hum Genet 1999 65[6] 1538—1546. 

Unlu M et al. Detection of complement factor B in the cerebrospinal fluid of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy disease using two-dimensional gel electrophoresis and mass spectrometry. Neurosci Lett 2000 282 149-152. 

Nunoi and co-workers (1988) fractionated neutrophil cytoplasm by Mono Q anion-exchange chromatography and obtained three fractions (NCF-1, -2 and -3) that were active in the assembly of the oxidase. Independently, Volpp and colleagues (Volpp, Nauseef Clark, 1988) prepared antiserum from cytosolic factors that eluted from a GTP-affinity column, and this antiserum (Bl) recognised cytoplasmic factors of relative molecular masses 47 kDa and 66 kDa. It was later shown by this group that these cytosolic factors translocated to the plasma membrane during activation. NCF-1 was shown to contain the 47-kDa protein and NCF-2 the 66-kDa protein. Analysis of the defect in the cytosol of autosomal recessive CGD patients revealed that most of these (88%) lacked the 47-kDa protein (p41 -phox), whereas the remainder lacked the 66-kDa protein (p66-phox). Both of these components have now been cloned and recombinant proteins expressed. Interestingly, in the cell-free system, recombinant p47-phox and p66-phox can restore oxidase activity of the cytosol from autosomal recessive CGD patients who lack these components. 

Nunoi, H., Rotrosen, D., Gallin, J. I., Malech, H. L. (1988). Two forms of autosomal chronic granulomatous disease lack distinct neutrophil cytosol factors. Science 242, 1298-1301. 

Reduced penetrance and variable expressivity are factors that influence the effects of particular genetic changes. These factors usually affect disorders that have an autosomal dominant pattern of inheritance, although they are occasionally seen in disorders with an autosomal recessive inheritance pattern. 

Parahemophilia is an autosomal recessive bleeding disorder characterized by a reduced plasma concentration of the Factor V blood copulation protein. Deficiency arises from a 12 base-pair deletion in the Factor V gene that impairs the secretion of Factor V by hep-atocytes and results in an abnormal accumulation of immunoreactive Factor V antigen in the cytoplasm. In which region of the Factor V gene would this mutation most likely be located ... 

Because males have only one X chromosome, gene frequency estimation for X-Hnked traits differs from that of autosomal traits. Consider hemophilia A (Chapter 1), which is an X-linked recessive disease. If a male s X chromosome has a factor VIII mutation, he will have hemophilia A. If his X chromosome does not have the mutation, he will not develop the disease. Thus, the gene frequency for hemophilia A is obtained simply by counting the proportion of affected males in the population (i.e., the proportion of X chromosomes containing the mutation). Approximately one in 10,000 males has hemophilia A. Thus, the gene frequency for this disease, q, is 1/10,000. 

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