C. Sikström

Orosomucoid Polymorphism in Finns, Swedes and Swedish Saamis

Genetic polymorphism of orosomucoid (ORM) was studied by isoelectric focusing and immunoblotting in Finns, Swedes and Swedish Saamis. The ORM2 locus was found to be monomorphic in all three ethnic groups. In the Swedish sample the frequency of the ORM1*2 allele (0.414) was within the range found in other European populations, whereas Finns (0.282) and Saamis (0.210) showed significantly lower ORM1*2 frequencies. The extremely low ORM1*2 frequency in the Saamis further underlines the genetic uniqueness of this population. The ORM1*2 frequency in Saamis resembles those in Asiatic Mongoloid populations, but this is unlikely to reflect an Asiatic influence, since the accumulated knowledge on genetic markers in the Saamis show no unequivocal evidence for an Asiatic influence in this population.

Three novel spermatogenesis-specific zinc finger genes.

We have cloned and characterized the expression, during spermatogenesis, of three novel zinc finger genes (Zfp94, Zfp95, Zfp96). Analysis of the deduced protein sequences reveals that all three molecules belong to the LeR family (leucine‐rich zinc fingers) and that ZFP95 contains a domain homologous to the Krüppel‐associated box. All three genes were found expressed at high levels in testis among other tissues, but testis‐specific transcripts were observed for Zfp95 and Zfp96. Northern blot analyses of the testis‐specific transcripts of Zfp95 and Zfp96 were performed using whole testis RNA as well as RNA isolated from enriched populations of specific spermatogenic cell types. The testis‐specific transcript of Zfp95 showed the highest expression in pachytene spermatocytes, while that of Zfp96 was highly expressed in pachytene spermatocytes, in round spermatids and residual bodies. Northern blot analysis of RNA from the testis of mice carrying the atrichosis mutation further validated these expression patterns. In particular, the testis‐specific transcripts of Zfp95 and Zfp96 were greatly reduced in heterozygous, and completely absent in homozygous testis RNA from atrichosis mutant mice, further defining the germ cell specificity of these transcripts.

DNA Polymorphisms and Haplotypes of Human Liver/Bone/Kidney Alkaline Phosphatase in Finns, Saamis and Swedes

BclI and SstI restriction fragment length polymorphisms of human liver/bone/kidney or tissue-non-specific alkaline phosphatase were studied in population samples of Finns, Swedes and Swedish Saamis. No significant allele frequency differences were found between the three ethnic groups, but in comparison with a previously reported study of North American Caucasians, a highly significant difference was found with respect to BclI alleles. In contrast to previous findings, a significant linkage disequilibrium was found between BclI and SstI alleles.

Serum Complement (C3, BF, C4) Types in Swedish Saamis

Serum complement (C3, BF, C4) types were examined in Swedish Saamis (Lapps). In agreement with previous studies, a very low frequency of the C3*F allele (0.033) was found. Compared to Swedes and other Caucasian populations, Swedish Saamis showed a significantly increased frequency of the BFS, C4A4 and C4B2 variants, and a lower frequency of C4 deficiency. BFS, C4A4 and C4B2 show haplotype associations and thus the frequency of the S-A4-B2 complotype is significantly increased among the Saamis. Although the serum complement constitution of the Saamis shows some similarity with that of Asiatic Mongoloid populations it is unlikely to be due to Asiatic ethnic influence. The marked genetic deviations of the Saamis from all other populations has often been interpreted as a result of the founder effect and genetic drift. In this particular case, however, immunogenetic adaptation appears to be a plausible alternative explanation for the deviations in genetic complement factors.

GC Serum Groups and Otosclerosis

Five genetic serum protein marker systems (HP, TF, GC, BF and PI) were studied in patients with otosclerosis and in controls. The distributions of GC phenotypes and alleles showed significant differences between patients and controls with an excess of the IF-allele and the IF-variant among the patients.

Correlation between RsaI restriction fragment length polymorphism and electrophoretic types of human placental alkaline phosphatase

Restriction fragment length polymorphism (RFLP) of human alkaline phosphatases was studied in a population sample from northern Sweden using a placental alkaline phosphatase (PLAP) cDNA probe. After digestion of human genomic DNA with RsaI the Southern blots showed DNA fragments most probably derived from three genes: PLAP, germ cell alkaline phosphatase (PLAP-like) and intestinal alkaline phosphatase. In agreement with a previous study, a two-allele polymorphism was found in PLAP with bands at 1.6 kilobases (A1) and 1.8 kilobases (A2). The gene frequencies of A1 and A2 were 0.46 and 0.54, respectively. There was a significant correlation between the RsaI RFLPs and electrophoretic types of PLAP; RSAI A2 showed an association with the ALP2p allele of PLAP.

Ethnic Differences in Enzyme and DNA Polymorphisms of Human Tissue-Specific Alkaline Phosphatases

Enzyme and DNA polymorphisms and haplotypes of tissue-specific alkaline phosphatase genes were studied in Finns, Saamis and Swedes. In placental alkaline phosphatase (PLAP) restriction fragment length polymorphisms (RFLPs), found after digestion with RsaI and PstI, no significant population differences were observed. The PstI RFLP of the germ cell alkaline phosphatase (GCAP) locus showed significant allele frequency variations between Finns and Swedes (p = 0.014) and between Saamis and Swedes (p = 1 x 10(-4)). Electrophoretic enzyme variants of PLAP were studied in Finns and Swedes. The PLAP variant 18 (D in older nomenclature) was found at a polymorphic frequency in the Finnish sample. In all populations, strong linkage disequilibria were found between the RFLPs and between RFLPs and electrophoretic PLAP types. There was, however, one notable exception: between the RsaI RFLP of PLAP and the PstI RFLP of GCAP no linkage disequilibrium was found. Two new RFLPs were observed in the Finnish population sample, a RsaI mutant site in PLAP with a frequency of 0.02 and a KpnI mutant site outside and upstream of the PLAP gene with a frequency of 0.036. In accordance with findings in previous studies at the enzyme level, PLAP also appeared to be more polymorphic than GCAP and intestinal alkaline phosphatase at the DNA level.

A New PstI Restriction Fragment Length Polymorphism (RFLP) of Placental Alkaline Phosphatase

A new PstI restriction fragment length polymorphism (RFLP) of placental alkaline phosphatase (PLAP) was discovered in a study of a Finnish population sample and designated PstI(b)1 or Pst(b)2 depending on the presence or absence of the cleavage site. The frequency of the PstI(b)2 allele was 0.24. This allele showed a positive (p = 3 x 10(-6) association with the electrophoretic allele 2(F) and a negative association (2 x 10(-7) with the electrophoretic allele 1(S). The previously described PstI RFLP [PstI(a)] was also found to be associated with electrophoretic types; the PstI(a)1 allele (presence of site) was associated with the electrophoretic type 2 (p = 0.023). Haplotype frequencies and disequilibria were calculated between PstI(a), PstI(b) and RsaI RFLPs. A complete disequilibrium (p = 1 x 10(-6) was found between PstI(a) and RsaI, whereas there was no significant disequilibrium between PstI(b) and RsaI. There was no strict correlation between the distances between the RFLP loci and the degree of linkage disequilibrium. The allele controlling the electrophoretic variant PLAP 18 (D) was found in polymorphic frequency (0.024) in the Finnish population.

PstI Restriction Fragment Length Polymorphism of the Human Intestinal Alkaline Phosphatase Gene

Restriction fragment length polymorphisms have previously been found in the placental alkaline phosphatase (PLAP) and germ cell alkaline phosphatase (GCAP) genes, but not in the closely related intestinal alkaline phosphatase (IAP) locus. We here report on a PstI restriction fragment length polymorphism in IAP found in Finns and Swedes but not in Saamis. A probable T-->G mutation in position 175 of intron 11 would create a new cleavage site for PstI. The borderline frequency of the mutant allele (0.01) is in agreement with previous observations suggesting that IAP is considerably less polymorphic than PLAP and GCAP.

RsaI and BclI polymorphism of the transferrin receptor gene.

Polymorphism of the transferrin receptor gene has previously not been observed. Here we report two new restriction fragment length polymorphisms (RFLPs) of the transferrin receptor gene. Digestion with RsaI revealed three variable fragments at 1.15, 1.05 and 0.85 kb. After cleavage with BclI, two polymorphic 2.8- and 2.3-kb fragments were found. There was strong linkage disequilibrium between the two RFLPs, and Saamis showed a highly significant difference from Finns and Swedes with respect to allele frequencies. The new polymorphisms of the transferrin receptor gene may be useful markers in population and linkage studies and in studies of associations with body iron stores and susceptibility to genotoxic damage and cancer.