72 



CHAPTER 6 



of the body, leading to the malfunctions oi 



all the organs already mentioned; in addi- 

 tion, these defective corpuscles are readilj 

 destroyed by the body, with consequent 



anemia. 



We see. then, that the apparently unre- 

 lated phenotypic effects of the gene for 

 sickling are merely consequences of the sick- 

 ling of red blood cells. Moreover, biochem- 

 ical studies show that sickling itself is the 

 result of the presence of an abnormal type 

 of hemoglobin (having a slightly lower oxy- 

 gen-carrying capacity than normal hemo- 

 globin) which sickle-cell homozygotes carry 

 in their red blood cells. There is. therefore, 

 a pedigree of causes for the multiple effects 

 of the gene for sickling. The first cause is 

 the gene, the second is the abnormal hemo- 

 globin it produces, the third is the sickling 

 that follows, and the fourth is the subsequent 

 red cell clumping and destruction which pro- 

 duce gross organic defects and anemia. 



In this case all the pleiotropic effects are 

 attributed to a single biochemical action of 

 a gene. This single action then affects many 

 varied chemical reactions involved in the 

 production of different, at first apparently 

 unrelated, traits. In view of the Himalayan 

 rabbit and sickle-cell anemia studies, one 

 may even hypothesize that most, if not all, 

 genes have a single primary phenotypic ac- 

 tivity. The pleiotropic effects described in 

 other cases may yet prove, upon further 

 analysis, to be tertiary or even further re- 

 moved effects in a pedigree of causes, the 

 primary cause being genie and the single 

 secondary cause still undetermined. Reply- 

 ing to the question with which this section 

 started, the simplest hypothesis is that most, 

 if not all, genes have only one phenotypic 

 activity; this gene action has a pedigree of 

 effects which results in pleiotropism. 



Penetrance and Expressivity 



Analysis of the genetic material has been 

 greatly facilitated by the particular traits we 



have chosen to study. The most valuable 

 kind of trait has been one based upon a 

 genotype that always expresses itself in ap- 

 proximately the same way, despite the nor- 

 mal fluctuations of the environment. 



Consider, however, a pedigree for Poly- 

 dactyly (Figure 6-5), a rare condition in 

 which human beings have more than five 

 digits on a limb. In the figure, the topmost 

 female is affected, having five fingers on each 

 hand and six toes on each foot. Her hus- 

 band is normal in this respect. This couple 

 has five children, three affected. This sug- 

 gests that Polydactyly is due to a single domi- 

 nant gene, P, and that the mother is Pp, the 

 father pp. Consistent with this hypothesis 

 is the result of the marriage of one of their 

 affected daughters to a normal man. This 

 marriage produced two sons, one of whom 

 is affected, and this affected son, in turn, 

 has five children including some affected and 

 some unaffected. 



But now examine the left side of this pedi- 

 gree. Note the firstborn son who is un- 

 affected yet has an affected daughter. How 

 may this be explained? It might be sup- 

 posed that this son is genotypically pp and 

 that his daughter is Pp, the P having been 

 produced by mutation of p, then contributed 

 to the daughter at conception. However, 

 other pedigrees for Polydactyly also have 

 cases in which two normal individuals have 

 an affected child. Since Polydactyly is rare, 

 mutations from p to P must be still more 

 rare, so that the chance for such a mutant 

 to appear in a sex cell of one of two normal 

 parents is very small. It is most improbable, 

 then, that such a rare mutation, if it occurs 

 at random among normal individuals, would 

 occur so often among the normals in pedi- 

 grees for Polydactyly. 



A different explanation is that the firstborn 

 son is in fact Pp, where P is not expressed 

 in any detectable way, although it is ex- 

 pressed in his daughter. This interpreta- 

 tion is supported by the kind of expression 



