Ilaria Boschi

The Analysis of Variation of mtDNA Hypervariable Region 1 Suggests That Eastern and Western Pygmies Diverged before the Bantu Expansion

The Eastern Pygmies from Zaire and Western Pygmies from Cameroon, Congo, and the Central African Republic represent the two principal groups of African Pygmies. In the “recent divergence” hypothesis in which Western Pygmies are thought to be the result of hybridization between the ancestors of Eastern Pygmies and Bantu farmers who penetrated the equatorial belt and came into contact with Pygmies around 2–3 kiloyears ago. On the basis of recent archaeological research in the tropical rain forest, we propose a “pre‐Bantu divergence” hypothesis, which posits the separation between the ancestors of Eastern and Western Pygmies earlier than 18 kiloyears ago. In order to test the two hypotheses, we analyzed the variation of the hypervariable region 1 of the mitochondrial DNA in the Mbenzele, Western Pygmies of the Central African Republic, and compared our results with those of previous mtDNA and Y chromosome studies. Distribution, sequence variation, and age of haplogroups along with genetic distances among populations, estimates of divergence times, and simulations based on the coalescent approach were found to be congruent with the pre‐Bantu divergence but failed to support the recent divergence hypothesis.

State of the art in forensic investigation of sudden cardiac death.

The sudden death of a young person is a devastating event for both the family and community. Over the last decade, significant advances have been made in understanding both the clinical and genetic basis of sudden cardiac death. Many of the causes of sudden death are due to genetic heart disorders, which can lead to both structural (eg, hypertrophic cardiomyopathy) and arrhythmogenic abnormalities (eg, familial long QT syndrome, Brugada syndrome). Most commonly, sudden cardiac death can be the first presentation of an underlying heart problem, leaving the family at a loss as to why an otherwise healthy young person has died. Not only is this a tragic event for those involved, but it also presents a great challenge to the forensic pathologist involved in the management of the surviving family members. Evaluation of families requires a multidisciplinary approach, which should include cardiologists, a clinical geneticist, a genetic counselor, and the forensic pathologist directly involved in the sudden death case. This multifaceted cardiac genetic service is crucial in the evaluation and management of the clinical, genetic, psychological, and social complexities observed in families in which there has been a young sudden cardiac death. The present study will address the spectrum of structural substrates of cardiac sudden death with particular emphasis given to the possible role of forensic molecular biology techniques in identifying subtle or even merely functional disorders accounting for electrical instability.

J1-M267 Y lineage marks climate-driven pre-historical human displacements.

The present day distribution of Y chromosomes bearing the haplogroup J1 M267*G variant has been associated with different episodes of human demographic history, the main one being the diffusion of Islam since the Early Middle Ages. To better understand the modes and timing of J1 dispersals, we reconstructed the genealogical relationships among 282 M267*G chromosomes from 29 populations typed at 20 YSTRs and 6 SNPs. Phylogenetic analyses depicted a new genetic background consistent with climate-driven demographic dynamics occurring during two key phases of human pre-history: (1) the spatial expansion of hunter gatherers in response to the end of the late Pleistocene cooling phases and (2) the displacement of groups of foragers/herders following the mid-Holocene rainfall retreats across the Sahara and Arabia. Furthermore, J1 STR motifs previously used to trace Arab or Jewish ancestries were shown unsuitable as diagnostic markers for ethnicity.

Estimating European admixture in African Americans by using microsatellites and a microsatellite haplotype (CD4/Alu)

We have analyzed 10 unlinked microsatellites and a linked Alu deletion polymorphism at the CD4 locus in an African American population sample from Chicago (USA). Heterozygosity estimates at the microsatellite loci range from 0.727±0.025 (D3S1358) to 0.873±0.017 (D18S51), with an average of 0.794±0.016. These values are comparable to or higher than those reported for Europeans, with only one exception (D3S1358). The CD4/Alu haplotypic diversity (0.887±0.012) is comparable to diversity levels observed in sub-Saharan African populations and is higher than the diversity levels reported in European populations. No consistent pattern of within, between, or multi-locus deviations from Hardy-Weinberg expectations is observed, suggesting a low sub-heterogeneity within the sampled population. We have applied a maximum likelihood method and estimated the proportion of European admixture to the African American gene pool to be 0.26±0.02. The narrow confidence interval indicates that allele frequency data from multiple microsatellite loci, whether analyzed independently or as haplotypes, are particularly useful for estimating genetic admixture.

Allele frequencies of fifteen STRs in a representative sample of the Italian population.

Fifteen autosomal short tandem repeat (STR) markers (D3S1358, HUMTH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, HUMvWA, D8S1179, HUMTPOX and FGA) were analyzed in more than 400 unrelated individuals from nine different areas of Italy. After Bonferroni correction, no evidence of population structure was identified, either by considering each population as independent or by combining populations according to their geographic origin (North, Central and South of Italy). Forensic indexes were estimated considering all samples together. Combined power of discrimination (PD) and combined power of exclusion (PE) for the 15 tested STR loci were 0.9999999997 and 0.964708775, respectively. Low genetic distances were found between our data and those previously published for other neighboring European populations.

Microsatellite variation in Central Africa: an analysis of intrapopulational and interpopulational genetic diversity

As a part of a research project on molecular variation in Central Africa, we have analyzed 10 microsatellites (CD4, CSFO, D3S1358, D18S51, D21S11, F13A1, FES, TH01, TPOX, and VWA) in the Bamileke and Ewondo from Cameroon and the Sanga and Mbenzele Pygmies from the Central African Republic (a total of 390 chromosomes). A statistically significant trend towards heterozygote deficiency was detected in the Mbenzele Pygmies. This was established through the use of powerful exact tests for the Hardy-Weinberg equilibrium. A certain degree of isolation and a small effective size may explain this finding. However, the lack of any substantial reduction in allelic diversity in the Mbenzele does not support the possibility that this group has a smaller effective size in evolutionary terms. A possible explanation based on ethnographic studies suggests that the gene flow from non-Pygmies to Pygmies could have been interrupted only in relatively recent times. The analysis of association between genotypes at pairs of independent loci indicates that the level of subheterogeneity is markedly lower in the Bamileke than in other sampled populations. This may be explained by the combined effect of larger population size, more rigid respect of clanic exogamy, and higher matrimonial mobility of the Bamileke. Finally, we have analyzed interpopulational relationships among our sampled populations and other Central African populations. The results are consistent with a previous study of protein loci (Spedini et al. 1999), which suggests the recent history of the Bamileke and Ewondo has led them to aquire a substantial genetic similarity. Furthermore, the Mbenzele Pygmies diverge from Biaka Pygmies, despite their common origin and geographical proximity. This is probably due to the differentiating effect of genetic drift, which is enhanced by the small effective size of Pygmy populations.

Increased forensic efficiency of a STR-based Y-specific haplotype by addition of the highly polymorphic DYS385 locus

Abstract The polymorphic short tandem repeat (STR) locus DYS385 mapping to the male-specific region of human Y chromosome, was used to reinvestigate 125 unrelated Italian males, from our data archive, who had been previously typed for 7 different Y-specific STRs (DYS19, DYS389 I and II, DYS390, DYS391, DYS392, DYS393), defining a haplotype now widely adopted in the forensic context. The aim of this study was to improve the information value of the original haplotype in view of its application to issues of personal identification and parental analysis. DYS385 proved to be highly polymorphic (94.5% gene diversity) and the overall individualization capacity of the 8-loci haplotype was raised to 93.6%, with 117 unique assets out of 125 tested samples.

Moors and Saracens in Europe : estimating the medieval North African male legacy in southern Europe

To investigate the male genetic legacy of the Arab rule in southern Europe during medieval times, we focused on specific Northwest African haplogroups and identified evolutionary close STR-defined haplotypes in Iberia, Sicily and the Italian peninsula. Our results point to a higher recent Northwest African contribution in Iberia and Sicily in agreement with historical data. southern Italian regions known to have experienced long-term Arab presence also show an enrichment of Northwest African types. The forensic and genomic implications of these findings are discussed.

2006 GEP-ISFG collaborative exercise on mtDNA: reflections about interpretation, artefacts, and DNA mixtures

We report the results of the seventh edition of the GEP-ISFG mitochondrial DNA (mtDNA) collaborative exercise. The samples submitted to the participant laboratories were blood stains from a maternity case and simulated forensic samples, including a case of mixture. The success rate for the blood stains was moderate ( approximately 77%); even though four inexperienced laboratories concentrated about one-third of the total errors. A similar success was obtained for the analysis of mixed samples (78.8% for a hair-saliva mixture and 69.2% for a saliva-saliva mixture). Two laboratories also dissected the haplotypes contributing to the saliva-saliva mixture. Most of the errors were due to reading problems and misinterpretation of electropherograms, demonstrating once more that the lack of a solid devised experimental approach is the main cause of error in mtDNA testing.

Evidence of high genetic variation among linguistically diverse populations on a micro-geographic scale: a case study of the Italian Alps

Although essential for the fine-scale reconstruction of genetic structure, only a few micro-geographic studies have been carried out in European populations. This study analyzes mitochondrial variation (651 bp of the hypervariable region plus 17 single-nucleotide polymorphisms) in 393 samples from nine populations from Trentino (Eastern Italian Alps), a small area characterized by a complex geography and high linguistic diversity. A high level of genetic variation, comparable to geographically dispersed European groups, was observed. We found a difference in the intensity of peopling processes between two longitudinal areas, as populations from the west-central part of the region show stronger signatures of expansion, whereas those from the eastern area are closer to the expectations of a stationary demographic state. This may be explained by geomorphological factors and is also supported by archeological data. Finally, our results reveal a striking difference in the way in which the two linguistically isolated populations are genetically related to the neighboring groups. The Ladin speakers were found to be genetically close to the Italian-speaking populations and differentiated from the other Dolomitic Ladins, whereas the German-speaking Cimbri behave as an outlier, showing signatures of founder effects and low growth rate.