shown by Herman Kalckar and co-workers 

 at the National Institutes of Health. The con- 

 dition may be alleviated by withholding milk 

 from the diet. This is difficult, however, be- 

 cause milk is used in the preparation of 

 many foods. 



The enzyme deficiencies of sickle cell ane- 

 mia and agammaglobulinemia are both con- 

 cerned with faulty protein synthesis. In the 

 sickle cell patient, the determining gene ap- 

 pears to carry a defective code (p. 526) for the 

 synthesis of hemoglobin. The amino acid se- 

 quence in this peptide chain is almost per- 

 fect, except that valine is substituted for 

 glutamic acid at one point. As a result of the 

 defect, the erythrocytes are not biconcave 

 discs. Instead, they are sickle-shaped (con- 

 cavo-convex), they have a faulty oxygen- 

 binding capacity, and they are abnormally 

 fragile. The anemia that results may be very 

 mild, in the case of heterozygous individuals, 

 or quite severe, when the homozygous condi- 

 tion obtains. This indicates, of course, that 

 the "sickle cell gene" is not completely re- 

 cessive to its normal allele. 



The code carried by the "agammoglobulin 

 gene" appears to be hopelessly scrambled, 

 since the gamma globulin fraction of the 

 plasma proteins is absent. This, of course, is 

 the "antibody fraction" and consequently 

 agammaglobulinemic patients are exceed- 

 ingly susceptible to infection (p. 320). 



Chromosomes of Man; Normal and Ab- 

 normal Complements. The diploid comple- 

 ment of chromosomes in man was difficult to 

 determine precisely. Man's chromosomes are 

 numerous and they are crowded together in 

 the metaphase plate (p. 46). Moreover, there 

 are only small differences in the size and 

 morphology of the various pairs, as is shown 

 in Figure 26-27. 



An early approach toward an accurate pic- 

 ture of man's chromosomes was made by T. 

 S. Painter at the University of Texas in 1921. 

 Painter counted 24 pairs, and this count was 

 generally accepted until 1956. Meanwhile, 

 the counting problem was greatly simplified 

 by the development of three techniques: (1) 



Heredity - 507 



the tissue culture technique, which enabled 

 the investigator to study the division stages 

 of human cells, particularly leucocytes, after 

 removal from the body; (2) the use of col- 

 chicine to block mitosis at metaphase, when 

 the chromosomes are very clearly differ- 

 entiated; and (3) the use of hypotonic media 

 to separate the chromosomes from one an- 

 other more sharply. 



In 1956, J. H. Tjio and A. Levan in Sweden 

 and C. £. Ford and J. L. Hamerton in Eng- 

 land were able to achieve the first perfect 

 counts — counts that have been verified sub- 

 sequently by many workers throughout the 

 world. Therefore it can now be said without 

 equivocation that man's normal complement 

 of chromosomes is 23 pairs: 22 pairs of auto- 

 somes and 1 pair of sex chromosomes, as is 

 shown in Figure 26-27. 



The newly developed accuracy of counting 

 has led to some important medical discov- 

 eries. It now is known definitely that at least 

 three serious pathological conditions — mon- 

 golism, the Klinefelter syndrome, and the 

 Turner syndrome — are related to abnormal- 

 ities in the chromosome constitution. In some 

 cases, an extra chromosome may be present; 

 but in other cases, a chromosome may be 

 missing. 



Mongolism, an unfortunate term as well 

 as an unfortunate condition, results from the 

 presence of an extra member of pair 21 (Fig. 

 26-27). Or, more technically stated, the mon- 

 goloid condition is related to trisomy in chro- 

 mosome 21. During oogenesis, apparently, 

 nondisjunction (p. 515) occurs in this pair of 

 chromosomes, resulting in the formation of 

 an egg that is diploid for this pair. Such non- 

 disjunction is relatively rare, however. Only 

 1 in 650 cases appears among children gen- 

 erally. However, the incidence among chil- 

 dren produced by older mothers (but not by 

 older fathers) reaches 3 percent when the 

 mother's age is 45 or over. The term "mon- 

 goloid" is apt only in the sense that such 

 children display an extra fold of skin in the 

 upper eyelid, giving an oriental appearance 

 to the eyes. The more serious aspects of the 



