G.F. De Stefano

mtDNA History of the Cayapa Amerinds of Ecuador: Detection of Additional Founding Lineages for the Native American Populations

mtDNA variation in the Cayapa, an Ecuadorian Amerindian tribe belonging to the Chibcha-Paezan linguistic branch, was analyzed by use of hypervariable control regions I and II along with two linked regions undergoing insertion/deletion mutations. Three major maternal lineage clusters fit into the A, B, and C founding groups first described by Schurr and colleagues in 1990, whereas a fourth lineage, apparently unique to the Cayapa, has ambiguous affinity to known clusters. The time of divergence from a common maternal ancestor of the four lineage groups is of sufficient age that it indicates an origin in Asia and supports the hypothesis that the degree of variability carried by the Asian ancestral populations into the New World was rather high. Spatial autocorrelation analysis points out (a) statistically significant nonrandom distributions of the founding lineages in the Americas, because of north-south population movements that have occurred since the first Asian migrants spread through Beringia into the Americas, and (b) an unusual pattern associated with the D lineage cluster. The values of haplotype and nucleotide diversity that are displayed by the Cayapa appear to differ from those observed in other Chibchan populations but match those calculated for South American groups belonging to various linguistic stocks. These data, together with the results of phylogenetic analysis performed with the Amerinds of Central and South America, highlight the difficulty in the identification of clear coevolutionary patterns between linguistic and genetic relationships in particular human populations.

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity

N-acetyltransferase 2 (NAT2), an important enzyme in clinical pharmacology, metabolizes antibiotics such as isoniazid and sulfamethoxazole, and catalyzes the transformation of aromatic and heterocyclic amines from the environment and diet into carcinogenic intermediates. Polymorphisms in NAT2 account for variability in the acetylator phenotype and the pharmacokinetics of metabolized drugs. Native Americans, settled in rural areas and large cities of Latin America, are under-represented in pharmacogenetics studies; therefore, we sequenced the coding region of NAT2 in 456 chromosomes from 13 populations from the Americas, and two from Siberia, detecting nine substitutions and 11 haplotypes. Variants *4 (37%), *5B (23%) and *7B (24%) showed high frequencies. Average frequencies of fast, intermediate and slow acetylators across Native Americans were 18, 56 and 25%, respectively. NAT2 intra-population genetic diversity for Native Americans is higher than East Asians and similar to the rest of the world, and NAT2 variants are homogeneously distributed across native populations of the continent.

New Data on the World Distribution of Paraoxonase (PON1 Gln 192→Arg) Gene Frequencies

The physiological role of human paraoxonase (PON), a serum enzyme that hydrolyzes organophosphate insecticides and nerve agents, is not clear. Of the three genes in the paraoxonase gene family, PON1 shows a polymorphism, Gln 192-> Arg, governed by two common alleles named *Q and *R. These determine two different isoforms associated, respectively, with lower and higher activity towards paraoxon, a toxic metabolic product of the insecticide parathion. The *R allele has often been found associated with an increased risk of coronary heart disease. As human populations tend towards greater exposure to environmental changes, including changes in dietary habits and contact with insecticides or other toxic substances, health risks will change as well. In studying the prevention of these newly emerging risks, it could be important to know the distribution of the two alleles in the various world populations. In this paper we report on the genotype and allele frequencies of this polymorphism in different populations, most of which have never been examined for this polymorphism. Samples were taken from mainland Italy, Sardinia, Ethiopia, Benin, and Ecuador. The *R allelefrequencies for the samples were: 0.313, 0.248, 0.408, 0.612, and 0.789, respectively. The data show a large variability in allele frequencies, and, in particular, that PON1 allele distribution depends on membership to different geographic populations.

The AluI-induced bands in great apes and man: implication for heterochromatin characterization and satellite DNA distribution

Restriction endonucleases have recently been proved to be active on fixed chromatin, producing differences in staining of metaphase chromosomes. In this paper we show the results obtained by treating the metaphase chromosomes of Pan troglodytes, Pan paniscus, and Gorilla gorilla with the restriction enzyme AluI. These results demonstrate qualitative differences in the telomeric heterochromatin between Pan and Gorilla despite the fact that these areas appear homogeneous in the two genera by the C-banding method. The results found with individual chromosomes in the different species also appear relevant, in the light of the evolutionary relationships between these nonhuman primates and man. Lastly, the results suggest the presence, in great apes, of some highly repetitive DNA sequences different from the human satellites I-IV.

Genetic population structure of two African-Ecuadorian communities of Esmeraldas.

The genetic structure of two African-Ecuadorian communities, Rio Cayapas and Viche (Esmeraldas province, northwest Ecuador), was studied on the basis of ACP1, ADA, AK1, CA2, ESD, GLO1, G6PD, PGD, and PGM1 subtypes and thermostability, PGM2, HBbeta, F13A, F13B, ORM1, AHSG, C6, C7, and APOC2 gene frequency, and migration data on 255 individuals. The fixation index of Wright (F(ST)), correspondence, and genetic distance analysis were applied to compare the genetic relationships between these communities and other American populations of African ancestry. F(ST) values from the migration data and surname origins suggest that Rio Cayapas is genetically more isolated and shows less mobility and admixture than does Viche. The genetic admixture estimates indicate a large contribution of African genes to the gene pool of both communities (74.3% to 58.4%), whereas the proportion of the Amerindian component differs significantly (14.5% in Rio Cayapas to 27.6% in Viche).

Analysis of three RFLPs of the COL1A2 (type I collagen) in the Amhara and the Oromo of Ethiopia

Background : The present composition of the Ethiopian population is the result of a complex and extensive intermixing of different peoples of North African, Near and Middle Eastern, and south-Saharan origin. The two main groups inhabiting the country are the Amhara, descended from Arabian conquerors, and the Oromo, the most important group among the Cushitic people. With the exception of some surveys on the general Ethiopian populations, little is known about the degree of genetic differentiation between the Amhara and the Oromo. Aim : The study seeks to investigate the genetic structure of these two heterogeneous Ethiopian populations and to characterize their relationships with other African and Mediterranean peoples. Subjects and methods : Amhara and Oromo individuals ( n = 171) were analysed for three RFLPs (restriction fragment length polymorphisms) of the COL1A2 gene. To better define the genetic relationship between the two Ethiopian groups, and also between African and non-African peoples, genetic distances among Amhara, Oromo and other populations were estimated using the COL1A2 allele and haplotype frequencies, and the allele frequencies of 16 additional classical markers. Results : h 2 analysis applied to the COL1A2 allele and haplotype frequencies showed a small but statistically significant degree of heterogeneity between the two Ethiopian populations. Combining the information obtained from the three RFLP markers, a significant level of differentiation (Fst = 0.0147, p = 0.036) was also detected between Amhara and Oromo. The genetic distance analysis showed the separation between African and non-African populations, with the Amhara and Oromo located in an intermediate position. This pattern is consistent with the location of the two Ethiopian groups in other genetic analysis and with cultural data. Conclusions : The present findings suggest the presence of a differential level of genetic relatedness with south-Saharan peoples in the two Ethiopian groups, which could reflect their different history and seems to indicate the existence of genetic sub-structure within the country.

An investigation of human apolipoproteins B and E polymorphisms in two African populations from Ethiopia and Benin.

Three polymorphisms (XbaI, EcoRI, and Ins/Del) of the apolipoprotein B (APOB) gene and the polymorphism of apolipoprotein E (APOE) were investigated in two population samples of Amhara and Oromo origin from Ethiopia, and in two population samples of Bariba and Berba origin from Benin. No heterogeneity was observed within each major group. The cumulated frequencies of the APOB X+, R+, and D alleles for the Ethiopia and the Benin groups were 0.268 and 0.133, 0.958 and 0.818, 0.206 and 0.223, respectively. Regarding APOE, the cumulated allele frequencies of Ethiopia and Benin were 0.031 and 0.103 for ϵ*2 allele, 0.811 and 0.742 for ϵ*3, and 0.143 and 0.155 for ϵ*4, respectively. APOE typing performed at the protein level only in the Ethiopians revealed a variant allele, ϵ*5, found at the polymorphic level both in the Amhara and in the Oromo (cumulated frequency: 0.015). A tentative explanation for the higher frequencies of ϵ*4 and ϵ*5 alleles was sought in relation to the lifestyle and ethnicity of the two populations. Am. J. Hum. Biol. 11:297–304, 1999.

Survey of seven plasma protein polymorphisms in the Amhara and Oromo populations of Ethiopia

The Ethiopian population is very difficult to specify due to a very high degree of intermixing among different peoples. The two groups of the present study, the Amhara and Oromo, constitute 38% and 35% of the population, respectively. In order to investigate the genetic composition of the Amhara and Oromo, genetic polymorphisms of seven plasma proteins (F13A, F13B, ORM1, AHSG, C6, C7, and APOC2), already identified as useful anthropological markers, were studied. No statistically relevant differences were found between the two groups for all of the systems examined. ORM1 and F13A showed frequencies in the range observed in other populations of Caucasoid and Negroid origin. F13B, AHSG, and C6 displayed gene frequencies and a number of variant alleles that seem particular to these two groups. No variation was observed for C7 and APOC2. Correspondence and distance analyses were used to interpret and compare the gene frequencies of the Amhara and Oromo with those of other related populations. These methods locate Ethiopians in an intermediate position between African Blacks and a group of Caucasoid populations, confirming cultural and historical data.

CTG repeats distribution and Alu insertion polymorphism at myotonic dystrophy (DM) gene in Amhara and Oromo populations of Ethiopia

Myotonic dystrophy (DM) is a dominantly inherited neuromuscular disease, highly variable and multisystemic, which is caused by the expansion of a CTG repeat located in the 3´ untranslated region of the DMPK gene. Normal alleles show a copy number of 5–37 repeats on normal chromosomes, amplified to 50–3000 copies on DM chromosomes. The trinucleotide repeat shows a trimodal allele distribution in the majority of the examined population. The first class includes alleles carrying (CTG)5, the second class, alleles in the range 7–18 repeats, and the third class, alleles (CTG)≥19. The frequency of this third class is directly related to the prevalence of DM in different populations, suggesting that normal large-sized alleles predispose toward DM. We studied CTG repeat allele distribution and Alu insertion and/or deletion polymorphism at the myotonic dystrophy locus in two major Ethiopian populations, the Amhara and Oromo. CTG allele distribution and haplotype analysis on a total of 224 normal chromosomes showed significant differences between the two ethnic groups. These differences have a bearing on the out-of-Africa hypothesis for the origin of the DM mutation. In addition, (CTG)≥19 alleles were exclusively detected in the Amhara population, confirming the predisposing role of these alleles compared with the DM expansion-mutation.

The Alu I-induced bands in metaphase chromosomes of orangutan (Pongo pygmaeus)

SummaryRestriction endonucleases have been recently proved to be active on fixed chromosomes, thus they are useful in chromatin structure studies. Within this class of enzymes, Alu I is able to detect the presence and localization of highly repetitive DNA sequences in human and in other mammalian and dipteran species. In this paper the pattern obtained on fixed metaphase chromosomes of orangutan (Pongo pygmaeus) by Alu I digestion and Giemsa staining is shown. The results are discussed in the light of the distribution, in this species, of the I–IV human satellite DNAs. It is also suggested that in Pongo some highly repetitive sequences, different from the major human satellites, are present.