Genetic characterization of the ABO blood group in Neandertals

Background: The high polymorphism rate in the human ABO blood group gene seems to be related to susceptibility to different pathogens. It has been estimated that all genetic variation underlying the human ABO alleles appeared along the human lineage, after the divergence from the chimpanzee lineage. A paleogenetic analysis of the ABO blood group gene in Neandertals allows us to directly test for the presence of the ABO alleles in these extinct humans. Results: We have analysed two male Neandertals that were retrieved under controlled conditions at the El Sidron site in Asturias (Spain) and that appeared to be almost free of modern human DNA contamination. We find a human specific diagnostic deletion for blood group O (O01 haplotype) in both Neandertal individuals. Conclusion: These results suggest that the genetic change responsible for the O blood group in humans predates the human and Neandertal divergence. A potential selective event associated with the emergence of the O allele may have therefore occurred after humans separated from their common ancestor with chimpanzees and before the human-Neandertal population divergence.

A protocol describing the genetic correction of somatic human cells and subsequent generation of IPS cell

The generation of patient-specific induced pluripotent stem cells (iPSCPSCPSCs) offers unprecedented opportunities for modeling and treating human disease. In combination with gene therapy, the iPSCPSCPSC technology can be used to generate disease-free progenitor cells of potential interest for autologous cell therapy. We explain a protocol for the reproducible generation of genetically corrected iPSCPSCPSCs starting from the skin biopsies of Fanconi anemia patients using retroviral transduction with OCT4, SOX2 and KLF4. Before reprogramming, the fibroblasts and/or keratinocytes of the patients are genetically corrected with lentiviruses expressing FANCA. The same approach may be used for other diseases susceptible to gene therapy correction. Genetically corrected, characterized lines of patient-specific iPSCPSCPSCs can be obtained in 4–5 months.

A genomic analysis identifies a novel component in the genetic structure of sub-Saharan African populations

Studies of large sets of SNP data have proven to be a powerful tool in the analysis of the genetic structure of human populations. In this work, we analyze genotyping data for 2,841 SNPs in 12 Sub-Saharan African populations, including a previously unsampled region of south-eastern Africa (Mozambique). We show that robust results in a world-wide perspective can be obtained when analyzing only 1,000 SNPs. Our main results both confirm the results of previous studies, and show new and interesting features in Sub-Saharan African genetic complexity. There is a strong differentiation of Nilo-Saharans, much beyond what would be expected by geography. Hunter-gatherer populations (Khoisan and Pygmies) show a clear distinctiveness with very intrinsic Pygmy (and not only Khoisan) genetic features. Populations of the West Africa present an unexpected similarity among them, possibly the result of a population expansion. Finally, we find a strong differentiation of the south-eastern Bantu population from Mozambique, which suggests an assimilation of a pre-Bantu substrate by Bantu speakers in the region.

Origin and genetic differentiation of Three Mexican Native Groups (Purépechas, Triquis and Mayas): contribution of CODIS-STRs to the history of human populations of Mesoamerica

BACKGROUND: CODIS-STRs in Native Mexican groups have rarely been analysed for human identification and anthropological purposes. AIM:To analyse the genetic relationships and population structure among three Native Mexican groups from Mesoamerica.SUBJECTS AND METHODS: 531 unrelated Native individuals from Mexico were PCR-typed for 15 and 9 autosomal STRs (Identifiler™ and Profiler™ kits, respectively), including five population samples: Purépechas (Mountain, Valley and Lake), Triquis and Yucatec Mayas. Previously published STR data were included in the analyses. RESULTS:Allele frequencies and statistical parameters of forensic importance were estimated by population. The majority of Native groups were not differentiated pairwise, excepting Triquis and Purépechas, which was attributable to their relative geographic and cultural isolation. Although Mayas, Triquis and Purépechas-Mountain presented the highest number of private alleles, suggesting recurrent gene flow, the elevated differentiation of Triquis indicates a different origin of this gene flow. Interestingly, Huastecos and Mayas were not differentiated, which is in agreement with the archaeological hypothesis that Huastecos represent an ancestral Maya group. Interpopulation variability was greater in Natives than in Mestizos, both significant.CONCLUSION: Although results suggest that European admixture has increased the similarity between Native Mexican groups, the differentiation and inconsistent clustering by language or geography stresses the importance of serial founder effect and/or genetic drift in showing their present genetic relationships.

Genetic studies of the Roma (Gypsies): a review

Background: Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. Results: Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups.Conclusion: Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.

Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy

Background and aims: The aim of this study was to investigate the genetic aetiology of intrahepatic cholestasis of pregnancy (ICP) and the impact of known cholestasis genes (BSEP, FIC1, and MDR3) on the development of this disease. Patients and methods: Sixty nine Finnish ICP patients were prospectively interviewed for a family history of ICP, and clinical features were compared in patients with familial ICP (patients with a positive family history, n=11) and sporadic patients (patients with no known family history of ICP, n=58). For molecular genetic analysis, 16 individuals from two independently ascertained Finnish ICP families were genotyped for the flanking markers for BSEP, FIC1, and MDR3. Results: The pedigree structures in 16% (11/69) of patients suggested dominant inheritance. Patients with familial ICP had higher serum aminotransferase levels and a higher recurrence risk (92% v 40%). Both segregation of haplotypes and multipoint linkage analysis excluded BSEP, FIC1, and MDR3 genes in the studied pedigrees. Additionally, the MDR3 gene, previously shown to harbour mutations in ICP patients, was negative for mutations when sequenced in four affected individuals from the two families. Conclusions: These results support the hypothesis that the aetiology of ICP is heterogeneous and that ICP is due to a genetic predisposition in a proportion of patients. The results of molecular genetic analysis further suggest that the previously identified three cholestasis genes are not likely to be implicated in these Finnish ICP families with dominant inheritance.

Genetic markers of the Va/Ba balanced lethal strain of Drosophila subobscura

The Va/Ba strain, constructed by Sperlich et al. (1977), is the only balanced lethal strain in D. subobscura. It allows the production of homozygous O chromosomes and has been a useful tool not only to analyse chromosomal viabilities but also to obtain homokaryotypic lines (Mestres and Serra, 2008). Besides the morphological dominant mutations Va (Varicose) and Ba (Bare), other genetic markers have been characterized in this strain, some of them by our group and not described previously. Here we present a list of these markers.