**Part 1**

**Background of Genetic Disorder** 

**1** 

Kenji Ikehara

*Japan* 

**Origin of the Genetic Code** 

*The Open University of Japan, Nara Study Center International Institute for Advanced Studies of Japan* 

Genetic disorders are illnesses caused by abnormalities in genetic sequences and the chromosome structures. Most base substitutions, which may lead to genetic disorders, would be repressed to a low level as affecting only one person in every thousands or millions by replication repair systems and by robustness of the genetic code, which is discussed in this Chapter. But, once persons were suffered by the genetic disorders, they would probably get serious diseases during their lives. In addition, it is quite difficult to recover the substituted bases causing the genetic diseases to original bases, after persons were suffered by the rarely occurring genetic disorders. This makes a quite big problem of

The mutations causing the genetic disorders are scattered throughout genes and their neighboring regions as shown in Figure 1 (A). It is also known that many genetic diseases are induced by single-base substitutions or missense mutations including nonsense mutations in genetic regions encoding amino acid sequences of proteins. For instance, sickle-cell anemia, one of the classical genetic disorders, is caused by a one-base replacement at the sixth codon of the hemoglobin β-globin gene, from A to U, which results in one amino acid substitution from glutamic acid to valine, producing an abnormal type of hemoglobin called hemoglobin S (Figure 1 (B)). Hemoglobin S distorts the shape of red blood cells due to hemoglobin aggregation in the cells, especially when exposed to low oxygen levels, resulting in anemia giving a patient malaria resistance. Phenylketonuria (PKU), adenosine deaminase (ADA) deficiency and galactosemia are also caused by one-base replacements in genes of phenylalanine hydroxylase, adenosine deaminase and galactosidase, respectively (Table 1). Of course, deletion and insertion of a small number of bases causing frameshift mutations in a genetic sequence encoding protein may also affect normal life activities, because the frameshift mutation induce a change to different amino acid sequences following the mutation site. Base substitutions also may occur in transcriptional and translational control regions, splicing sites and so on, which affect various functions for gene expression leading to synthesis of lower or higher amounts of proteins than normal level, resulting in many kinds of genetic diseases

the genetic disorders from a stand point of medical treatment.

**1. Introduction** 

(Figure 1 (A)).

 **and Genetic Disorder** 
