G. Beckman

Y-Chromosomal Diversity in Europe Is Clinal and Influenced Primarily by Geography, Rather than by Language

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Is p53 polymorphism maintained by natural selection

We present here a new interesting feature of the human tumor suppressor gene p53: a very pronounced ethnic and clinal variation of polymorphic codon 72 alleles. The frequency of the A1 (Pro) allele showed a north-south cline from 17% in Swedish Saamis to 63% in African Blacks (Nigerians), and there was a significant (p < 0.001) correlation (r = 0.95) between the A2 frequency and latitude. In the Finnish and Swedish populations no significant differences were found with respect to the genotype and allele distributions in spontaneously aborted fetuses and liveborn children, which makes differential intrauterine selection unlikely. However, the ethnic and clinal variations suggest that the codon 72 polymorphism is balanced and maintained by natural selection.

p53 Polymorphisms and Haplotypes Show Distinct Differences between Major Ethnic Groups

Three different p53 DNA polymorphisms (a 16-bp duplication in intron 3 and BstUI and MspI RFLPs in exon 4 and intron 6, respectively) and haplotype combinations were studied in some major ethnic groups: Caucasians (Swedes), Chinese, Dravidian Indians and African Blacks. Significant ethnic differences in single polymorphisms were found between all groups except for African Blacks-Dravidian Indians, who differed only in their MspI7-16-bp duplication haplotype distribution. Since previous results have shown that p53 alleles are correlated with latitude (degree of insolation), the similarity between these two groups, who are genetically quite distinct, may be due to ecological adaptation to similar climatic conditions. All other major ethnic groups differed significantly from each other with respect to their haplotype distributions; thus, p53 alleles and haplotypes should be very useful as anthropological markers. Asiatic Mongoloid groups appear to be characterized by very low frequencies of the 16-bp duplication and the MspI A1 allele. These mutations have probably been introduced by migration to east Asia from either Europe or Africa, where the highest frequencies were found. The results of this study indicate that p53, besides its role as a tumor suppressor, shows distinct ethnic heterogeneity and may be involved in ecological (climatic) adaptation.

Superoxide Dismutase Isozymes in Different Human Tissues, Their Genetic Control and Intracellular Localization

Two isozymes of superoxide dismutase, A and B, were found in extracts of human organs, tissues and cell cultures. Differential centrifugation of cell homogenates revealed that isozyme A was localized

Association between the p21 Codon 31 A1 (arg) Allele and Lung Cancer

In previous investigations p53 polymorphisms and haplotypes have been found to be associated with different types of cancer. In this paper the codon 31 polymorphism of the p53-inducible protein p21 was studied in 144 Swedish lung cancer patients and two different control groups: 95 patients with chronic obstructive pulmonary disease (COPD) and 761 healthy controls. An increased frequency of the p21 codon 31 A1 (arg) allele was found in lung cancer patients, especially in comparison with COPD patients (p = 0.004). There was a significantly increased frequency among lung cancer patients of individuals carrying the arg allele both in comparison with COPD controls (OR = 5.2, 95% CI 1.5-18.1) and healthy controls (OR = 1.7, 95% CI = 1.0-2.9). The results of this and previous studies indicate that allelic variants of both p53 and its effector protein p21 may have an influence on lung cancer.

Ethnic Variation in the Mitochondrial Targeting Sequence Polymorphism of MnSOD

In contrast to CuZn superoxide dismutase (SOD), only a very limited number of mutations have been described in MnSOD. One interesting example is a polymorphism (Ala-9Val) in the mitochondrial targeting sequence of this radical-scavenging enzyme. We have studied the Ala-9Val polymorphism in various ethnic groups by means of the oligonucleotide ligation assay. There were significant variations in this unique polymorphism between three different language groups: Baltic (Lithuanians), Finnic (Finns and Saamis) and Germanic (Swedes). The Ala frequency in an Asiatic population (Chinese) was significantly lower than in most European populations. This polymorphism may affect the mitochondrial targeting rate of MnSOD which may result in mitochondrial damage with implication in various late-onset neurological diseases.

p53 Polymorphisms and Haplotypes in Nasopharyngeal Cancer

Three p53 DNA polymorphisms (BstUI and MspI RFLPs in exon 4 and intron 6, respectively, and a 16-bp duplication in intron 3) and their haplotype combinations were studied in 73 patients (61 males and 12 females) with nasopharyngeal cancer and 105 healthy controls from the Guizhou province in southern China. Increased frequencies of the 16-bp A2 allele (p = 0.005), MspI A1 allele (p = 0.021) and the BstUI A1 (Pro) allele (p = 0.072) were found among the patients, with more pronounced differences in male patients (p = 0.003, 0.014 and 0.052, respectively). Haplotype frequencies and linkage disequilibria differed from those in Caucasians. The differences between controls and patients, especially male patients, increased when the analysis was based on haplotypes. The lowest risk for nasopharyngeal cancer was associated with the haplotype 16-bp A1, BstUI A2, MspI A2 (1-2-2). A somewhat higher risk was observed in the 1-1-2 haplotype (replacing the Arg with a Pro allele). The highest risk was, however, found in the rare combinations including the 16-bp A2 and MspI A1 alleles with an odds ratio of 4.9 [95% confidence interval (CI) = 1.8-13.2] in all patients and 5.4 (95% CI = 2.0-14.8) in male patients. The haplotype associations found in this study differ from those found in previous cancer association studies in Caucasians. This together with the fact that the intronic markers conferred the highest risk figures suggest that the mechanism behind the observed associations is linkage disequilibrium and not direct functional involvement of the codon 72 alleles.

Serum Protein Markers in Systemic Lupus erythematosus

Serum protein markers (alpha 1-AT, Bf, C3, C4A, C4B, Hp and Tf) were studied in a series of 36 patients with systemic lupus erythematosus (SLE) and compared to normal blood donors. In agreement with the results of previous investigations a significant increase of complement C4 deficiency was found among the SLE patients. The relative risks for AQ0 and BQ0 homozygosity were 7.2 and 4.1, respectively. Simultaneous occurrence of AQ0 and BQ0 was found in three patients with a calculated relative risk of about 65. A significant increase of the haptoglobin type 2-2 (p less than 0.05) was found among SLE patients. The remaining serum protein systems showed no statistically significant associations with SLE.

Chromosomal Aberrations and Male Infertility

AbstractMitotic chromosome analyses performed on 342 consecutive men with infertility problems identified 32 (9.4 per cent) with chromosomal aberrations. Of these patients 7 had increased chromosomal breakage, while 25 had other chromosomal abnormalities. Sperm density and frequency of morphologically normal spermatozoa in the material seem to be informative and related to the occurrence of abnormal karyotypes. We conclude that all patients with either abnormal sperm density or a low frequency of morphologically normal spermatozoa should be considered for cytogenetic investigation.

Chromosome Aberrations in Psoriatic Patients Treated With Arsenic

SummaryA significantly increased frequency of chromosomal aberrations was found in lymphocytes from eight psoriatic patients previously treated with arsenic than in lymphocytes from eight psoriatics with no such previous treatment. In most patients the arsenic therapy was discontinued more than 15 years ago. In the arsenic-treated group a statistically significant heterogeneity was found with respect to the frequency of aberrations. The frequency of sister chromatid exchange was not increased in the arsenic-treated patients.