Recessive, genetic trait

Of 50 adult rats used in a reproductive/developmental study, 22% of those that received 6 mg/kg/day heptachlor in the diet developed lens cataracts 4.5-9.5 months following exposure. In addition, 6-8% of the pi offspring and 6% of the p2 offspring of these rats also developed cataracts 19-21 days after birth (Mestitzova 1967). The author of this study eliminated the possibility of a vitamin B deficiency or a recessive genetic trait as the cause of the cataracts. She could not rule out the possibility of altered vitamin B metabolism caused by heptachlor. 

Tay-Sachs disease is a lipid storage disease caused by an absence of the enzyme hexosaminidase, which functions in gan-glioside metabolism. As a result of the enzyme deficiency, the ganglioside, shown in Section 18.4, accumulates in the cells of the brain causing neurological deterioration, like Niemann-Pick disease, it is an autosomal recessive genetic trait that... 

The genetic trait for MH is not sex-linked and both men and women can inherit MH. Inheritance in humans appears to be autosomal dominant with variable penetrance. Studies of large families have documented an autosomal dominant pattern. McPherson and Taylor (1982) studied 93 families in whom MH occurred. Even though various patterns of inheritance did emerge in the study we should assume that 50% of children are at risk in MH susceptible families. Kalow and Britt (1992) suggested that, in some families, at least two different non-allelic genes are likely to be present, one of which is probably autosomal dominant but rare, and the other autosomal recessive but common. 

The most common forms of ichthyosis — autosomal dominant ichthyosis vulgaris (IV) and X-linked recessive ichthyosis (XRI) — in many countries occur at frequencies a high as 1/300 and 1/2500, respectively. In fact, the genetic traits for IV and XRI are so frequent that the two diseases sometimes coexist in one and the same family, which may cause confusion as to the inheritance pattern. Although the incidence of IV and XRI is probably similar around the world, climate differences in particular will affect the severity of the disease, and hence its notification by the health care system. 

Explain why the dominant-recessive genetic model is much simpler than most genetic trait determinations. 

His observations also led him to coin two terms that still persist in present-day genetics dominance for a trait that shows up in an offspring, and recessiveness for a trait masked by a dominant gene. 

Gene—Part of the genetic material that directs production of a particular protein, and thus determines the presence or absence of a particular trait. Genes may be dominant or recessive. 

Genetically determined defects in the phase I oxidative metabolism of debrisoquin, phenacetin, guanoxan, sparteine, phenformin, warfarin, and others have been reported (Table 4-4). The defects are apparently transmitted as autosomal recessive traits and may be expressed at any one of the multiple metabolic transformations that a chemical might undergo. 

Genetic factors that influence enzyme levels account for some of these differences. Succinylcholine, for example, is metabolized only half as rapidly in persons with genetically determined defects in pseudocholinesterase as in persons with normally functioning pseudocholinesterase. Analogous pharmacogenetic differences are seen in the acetylation of isoniazid (Figure 4-5) and the hydroxylation of warfarin. The defect in slow acetylators (of isoniazid and similar amines) appears to be caused by the synthesis of less of the enzyme rather than of an abnormal form of it. Inherited as an autosomal recessive trait, the slow acetylator phenotype occurs in about 50% of blacks and... 

A second well-studied genetic drug polymorphism involves the stereoselective aromatic (4)-hydroxylation of the anticonvulsant mephenytoin, catalyzed by CYP2C19. This polymorphism, which is also inherited as an autosomal recessive trait, occurs in 3-5% of Caucasians and 18-23% of Japanese populations. It is genetically independent of the debrisoquin-sparteine polymorphism. 

Genetic screening had reached a new stage in late 1960 when public health officials initiated voluntary screening of adults to detect heterozygous carriers of specific recessive traits, such as Tay-Sachs, another degenerative disease. Subsequently, several states passed laws to establish mandatory programs to screen for carriers of sickle-cell anemia. 

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