12pter ? 12p12.2: Possible Assignment of Human Triose Phosphate Isomerase

Marie-Odile Réthoré1, J. Cl. Kaplan2, Claudine Junien2, and J. Lejeune1

Human. Genet. 36, 235-237 (1977). Received November 26, 1976

Résumé :

Summary. Red cell triose-phosphate isomerase (TPI) was determined, together with other enzymes, in three patients with chromosome 12 abnormalities. In patient No. 1 (trisomy of the segment 12pter ? 12q12) and in patient No. 2 (trisomy of the segment 12pter ? 12p12.1), the TPI activity was significantly increased. In patient No. 3 (deletion of the segment 12p11 ? 12p12.2), the TPI activity was in the normal range. These results suggest that the human TPI locus is located an the chromosome 12 short arm, between 12pter and 12p12.2.


On the basis of linkage studies, the gene of human triose-phosphate isomerase (TPI) EC has been assigned to chromosome 12 (Jongsma et al., 1974). By hybridization experiments it has been further localized on the 12pter ? 12q14 region (Jongsma et al.,1975). We can now define its position :12pter ? 12p12.2. This conclusion results from quantitative estimation of TPI activity in 3 patients with different aberrations of chromosome 12.


Materials and Methods

The enzymatic activity of triose-phosphate isomerase has been assayed in three patients carrying a rearrangement of the short arm of chromosome 12:

Case No. 1 is a male of 2 years 4 months with trisomy of the segment 12pter ? 12q12 due to malsegregation of a maternal translocation t(12;14) (q12;p11). This patient's observation has been already reported (Réthoré et al., 1975),

Cage No. 2 is a newborn male with trisomy of the segment 12pter ? 12p12.1 due to malsegregation of a maternal translocation t(12;15) (p12; p11;1) (unpublished observation).

Case No. 3 is a 4-year-old male, with monosomy of the segment 12p11 ? 12p12.2, whose observation has been already reported (Malpuech et al., 1975).



Table 1 shows results concerning genes already assigned to chromosome 12 : triosephosphate isomerase (TPI), lactate dehydrogenase B (LDH P) (Malpuech et al., 1975; Réthoré et al.,1975) and glyceraldehyde 3 phosphate dehydrogenase (G3PD) (Réthoré et al., 1976). We also include, as controls, glucose 6 phosphate dehydrogenase and 6 phosphogluconate dehydrogenase, respectively assigned to chromosome X and chromosome 1 (Jangsma et al., 1973; First Internat. Workshop on Human Gene Mapping, 1973).

Table 1. Red cell enzyme activity estimated according to Beutler (1975).
Case No. 1Trisomy 12pter ? 12q12Case No.2Trisomy 12pter ? 12p12.1Case No. 3Monosomy 12p11 ? 12p12.2
Triose phosphate isomerase
InTris pH 8 (N= 1673 ± 374)281037001340
In sodium phosphate pH 7.5 (N = 2765 ± 288)55082192
Glyceraldehyde 3 phosphate dehydrogenase N=206 ± 29314 352 224 173
Lactadehydrogenase N = 100 ± 1513719045
Glucose 6-phosphate dehydrogenase N = 11.9 ± 1.4 11.210.810.2
6 Phosphogluconate dehydrogenase N = 9.1 ± 1.6
Results are expressed in lU/g Hb



Red cell TPI and G3PD activities are significantly increased in cases 1 and 2, while they are within normal limits in case 3. In contrast LDH, which is increased in cases 1 and 2, is significantly decreased in case 3. In addition, a study of TPI repeatedly showed an increased activity of leukocytes and fibroblasts in patient 1 (data not shown).

The excess of genetic material for chromosome 12 involves the short arm in its full length in case 1 and only the distal part in case 2. In case 3, there is a loss of genetic material, involving the proximal part. Only a short segment in the middle part of the short arm is concerned in all three aberrations, and, according to our previous results, the gene coding for LDH B was thereby assigned to this segment (Réthoré et al., 1975). Further investigations allowed us to localize G3PD on the distal segment (Réthoré et al., 1967). Since the results for TPI are similar to those obtained for G3PD, it is likely that the gene coding for TPI is located on the same distal segment of the short arm of chromosome 12 (Fig. 1).

As far as in chromosome aberrations gene dosage effect can provide a reliable clue to precise gene localisation (Junien et al.,1976), we suggest that the TPI locus, like G3PD, is between 12pter and 12p12.2.

Fig. 1. Localization of TPI, G3PD, and LDH-B on the chromosome 12 short arm. R banding according to Dutrillaux and Lejeune (1971)