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  • Title: [Searching for genetic markers--in the fields of forensic medicine and human genetics].
    Author: Ikemoto S.
    Journal: Nihon Hoigaku Zasshi; 1995 Dec; 49(6):419-31. PubMed ID: 8583686.
    Abstract:
    Research on genetic markers in the fields of forensic medicine and human genetics did not begin in earnest until 1968. Study of an extended family in Wakayama Prefecture resulted in the discovery of the variant Bm type in the ABO blood group system. This family of nearly 40 members composed of Group A, B, O and AB spouses and type Bm monozygotic twins provided the best research material possible. An extremely rare case of an individual with type O red blood cells but no anti-A or anti-B antibodies led to the discovery of type AmBm. Fishman and Mitsuhashi advocated the concept of immunogenetic RNA. We attempted to examine the immunogenetic RNA function by isolating RNA from the human spleen but obtained no definitive results. Many researchers had since examined the genetic markers in erythrocytes, leukocytes, serum proteins and blood cell enzymes, but research on genetic marker in saliva had not been advanced. We searched for genetic markers in the parotid saliva and developed the PmF and Ph systems. A salivary amylase variant and acid phosphatase polymorphism were also discovered. We elucidated the genetic structure and geographic gradinet of the salivary genetic markers, such as the Pa, Pb, Pr, Db and PIF systems, in Japanese. The genetic markers in the tear and saliva of mice and rats were also detected. We demonstrated RFLP polymorphism using an amylase cDNA probe. Our report was one of the first on polymorphism in the field of forensic medicine in Japan. Interest was also directed to polymorphism in platelet and we employed two-dimensional electrophoresis to establish the ThA and ThB systems which are controlled by autosomal codominant genes. Regarding the research on monoclonal antibody production and their application in forensic medicine, we cloned and produced antibodies for ABO, MN and Lewis grouping. Anti-glycopholin-A, anti-glycopholin-B and anti-glycolipid monoclonal antibodies were also produced and used to divide the red blood cell antigens roughly into three classes; the glycopholin-A (MN), glycopholin-B (Ss. Duffy Kell-Cellano, Lutheran, Diego, Xg) and the glycolipid (ABO, Lewis, P) classes. Red blood cell protein membrane proteases were also isolated from Nepenthes alata extract and lectin which are used in grouping animal blood cells. In the research on erythrocyte differentiation and erythrocyte group substance expression, we established a selective two phase liquid culture system for culturing precursor cells of peripheral erythrocytes, and demonstrated the expression of red blood cell antigens such as ABO, Rh and Duffy antigens in the early period (4 to 9 days) of Phase 2. Recently, research on identifying the genes which code for polymorphism in erythrocytes or erythrocyte enzymes is making progress. For example, a study indicated a possible relationship between an isoform of the glycophorin A gene and the MN variant. In the cDNA sequence of the Fy (a-b+) and (a + b-) types in the Duffy system, a GAT (Asp) to GGT (Gly) substitution in the codon for residual 44 was detected. Research on the Rh gene is being pursued energetically. Two clones of the Rh gene have been isolated; Rh Pl composed of 1251 bases, and Rh Pll estimated to be Ph PI with a base substitution at position 41 and an amino acid substitution at position 31. Seven isoforms of Ph Pl and 5 isoforms of Ph Pll have been obtained. The delineation of the Rh gene which contains as many as 50 types of Rh antigen genes is in progress. The red blood cell enzyme EsD system is also used commonly in the field of forensic genetics. In EsD polymorphism, type EsD1 contains G at base 569, type EsD2 contains A and type EsD1-2 shows a heterologous conjugation of G and A. Due to the development of immunosuppressive agents, bone marrow transplant can now be conducted even when the ABO and Rh systems are not compatible, as long as the HLA is compatible. In this case, all the erythrocyte polymorphic types or erythrocyte enzyme polymorphic types are transformed to t
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