1,721,203 research outputs found
Timing the first human migration into eastern Asia
No full textAbstract A recent report in BMC Biology indicates that modern humans first arrived in southern East Asia 60,000 years ago and settled the rest of East Asia from there. This early date and migration route has significant implications for our understanding of the origins of present-day human populations.</p
Pangenomics: A new era in the field of neurodegenerative diseases
Full text linkA pangenome is composed of all the genetic variability of a group of individuals, and its application to the study of neurodegenerative diseases may provide valuable insights into the underlying aspects of genetic heterogenetiy for these complex ailments, including gene expression, epigenetics, and translation mechanisms. Furthermore, a reference pangenome allows for the identification of previously undetected structural commonalities and differences among individuals, which may help in the diagnosis of a disease, support the prediction of what will happen over time (prognosis) and aid in developing novel treatments in the perspective of personalized medicine. Therefore, in the present review, the application of the pangenome concept to the study of neurodegenerative diseases will be discussed and analyzed for its potential to enable an improvement in diagnosis and prognosis for these illnesses, leading to the development of tailored treatments for individual patients from the knowledge of the genomic composition of a whole population
Apolipoprotein E (APOE) Haplotypes in Healthy Subjects from Worldwide Macroareas: A Population Genetics Perspective for Cardiovascular Disease, Neurodegeneration, and Dementia
No full textHuman APOE is a 299-amino acid long protein expressed and secreted in several tissues and body districts, where it exerts different functions mainly related to lipid metabolism, with specific activities around cholesterol transport and absorption/elimination. It has three main isoforms, determined by the pair of mutations rs7412-C/T and rs429358-C/T, which gives rise to the functionally different APOE variants ε2, ε3, and ε4. These have a distinct impact on lipid metabolism and are differentially implicated in Alzheimer’s disease and neurodegeneration, cardiovascular disease, and dyslipidemia. A plethora of other single nucleotide variants along the sequence of the APOE gene have been studied in cohorts of affected individuals, where they also modulate the influence of the three main isoforms to determine the risk of developing the disease. However, no contextual analysis of gene-long haplotypes has been carried out so far, and never extensively in cohorts of healthy individuals from different worldwide populations. Leveraging a rich population genomics dataset, this study elucidates the distribution of APOE variants and haplotypes that are shared across populations and to specific macroareas, revealing a variety of risk-allele associations that distinguish specific ancestral backgrounds and can be leveraged for specific ancestry-informed screenings in medicine and public health
Mitochondrial DNA variability in the Titicaca basin: Matches and mismatches with linguistics and ethnohistory.
No full textObjectives: The Titicaca basin was the cradle of some of the major complex societies of pre-Columbian South America
and is today home to three surviving native languages: Quechua, Aymara, and Uro. This study seeks to contribute
to reconstructing the population prehistory of the region, by providing a first genetic profile of its inhabitants, set also
into the wider context of South American genetic background.
Methods: We report the first mitochondrial DNA first hypervariable segment sequences of native populations of the
environs of Lake Titicaca: speakers of Aymara and Quechua, and the ‘‘Uros’’ of the Lake’s floating islands. We sampled
Aymara speakers from a locality where the Uro language was formerly documented, to check for possible language shift
patterns. These data are compared with those for other Amerindian populations, collated from already published sources.
Results: Our results uncover the genetic distinctiveness of our formerly Uro but now Aymara-speaking sample, in
contrast with a relative homogeneity for all the other Central Andean samples.
Conclusions: The genetic affinities that characterize Central Andean populations are highly consistent with the succession
of expansive polities in the region, culminating with the Incas. In the environs of Lake Titicaca, however, one
subset of the present day Aymara-speaking population exhibits a peculiar position: perhaps a genetic correlate to their
original Uro linguistic lineage (now extinct in the area), tallying with ethnohistorical claims for the distinctiveness of
the Uro population. Our results emphasize the need for genetic descriptions to consider the widespread phenomenon of
language shif
Genetic variation in taste receptor pseudogenes provides evidence for a dynamic role in human evolution
No full textBACKGROUND:
Human bitter taste receptors are encoded by a gene family consisting of 25 functional TAS2R loci. In addition, humans carry 11 TAS2R pseudogenes, some of which display evidence for substantial diversification among species, showing lineage-specific loss of function. Since bitter taste is thought to help prevent the intake of toxic substances, diversity at TAS2R genes could reflect the action of natural selection on the ability to recognize some bitter compounds rather than others. Whether species-specific variation in TAS2R pseudogenes is solely the result of genetic drift or whether it may have been influenced by selection due to different feeding behaviors has been an open question.
RESULTS:
In this study, we analyzed patterns of variation at human TAS2R pseudogenes in both African and non-African populations, and compared them to those observable in nonhuman primates and archaic human species. Our results showed a similar worldwide distribution of allelic variation for most of the pseudogenes, with the exception of the TAS2R6P and TAS2R18P loci, both of which presented an unexpected higher frequency of derived alleles outside Africa. At the TAS2R6P locus, two SNPs were found in strong linkage disequilibrium (r2 > 0.9) with variants in the functional TAS2R5 gene, which showed signatures of selection. The human TAS2R18P carried a species-specific stop-codon upstream of four polymorphic insertions in the reading frame. SNPs at this locus showed significant positive values in a number of neutrality statistics, and age estimates indicated that they arose after the homo-chimp divergence.
CONCLUSIONS:
The similar distribution of variation of many human bitter receptor pseudogenes among human populations suggests that they arose from the ancestral forms by a unidirectional loss of function. However we explain the higher frequency of TAS2R6P derived alleles outside Africa as the effect of the balancing selection acting on the closely linked TAS2R5 gene. In contrast, TAS2R18P displayed a more complex history, suggesting an acquired function followed by a recent pseudogenization that predated the divergence of human modern and archaic species, which we hypothesize was associated with adaptions to dietary changes
Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration
Full text linkGenetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. In the present study, 70 single-point mutations on the APP gene in a publicly available genetic dataset that included 2504 healthy individuals from 26 populations were scanned, and their distribution was analyzed. Furthermore, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations were detected in the worldwide dataset, with several of them being specific for a single individual, population, or macroarea. Patterns of segment sharing reflected recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementia
Y-STRs and RM Y-STRs Haplotype analysis in two populations of Romagna Region (North of Italy).
No full textExpanding X-chromosomal forensic haplotype frequencies database: Italian population data of four linkage groups
No full textRequests for solving complex kinship casework involving at least one female are increasing and in these circumstances the analysis of X-chromosomal STR markers plays a relevant role. Actually, it is well known the superior statistical power of X-STRs compared to autosomal markers in solving relationship when two sisters or half-sisters are involved and none of parents is available, in maternity testing or in cases involving close relatives as alternative putative fathers. In addition, the possibility to amplify more loci simultaneously and the strategy based on the analysis of four linkage groups to obtain the X-haplotype provide a powerful and validated tool. Nevertheless, haplotypes frequency distribution in different populations is still needed for calculation of probabilities in relationship testing. Published haplotype frequencies from German population data are available, but in different caseworks we found unreported X-haplotypes. To enlarge the forensic X-chromosome database, we present haplotype frequencies and other parameter of forensic interest obtained from 200 anonymous DNA samples of unrelated Italian males for the four linkage groups included in the Investigator Argus X-12 kit. From the comparison of the Italian sample haplotype frequencies with other populations, significant genetic distances were found with Asian and African populations, but not with Europeans. Finally, casework examples of complex kinship analysis are presented
Resolving the most common mtDNA control region haplotype by massively parallel sequencing: a pilot study in an Italian population sample.
No full textThe high mutation rate of mitochondrial (mt)DNA, its lack of recombination, its high abundance in the cell
and its greater resistance to environmental stress make the analyses of this molecule the most promising
choice in forensic genetics when nuclear markers fail to give reliable results. The control region (CR) shows
the highest variability and is therefore routinely typed in forensic studies. Coding region data are currently
used almost exclusively for a phylogenetic assignment of mtDNA haplotypes and in population genetic
studies. The extended analysis of the mitochondrial genome covering also the coding region is however
also useful in forensic applications, e.g. to further differentiate identical CR haplotypes.
The most frequent western Eurasian mtDNA CR haplotype 16519C-263G-315.1C (with respect to the
rCRS) has been observed in various sub-haplogroups of haplogroup R0 (Brandstätter et al., 2008). In the
current study 29 samples that displayed this haplotype were selected from a larger Italian population study
(Boattini et al., 2013) and sequenced for their coding region by massively parallel sequencing as previously
described (Parson et al., 2013).
The obtained complete mtGenome haplotypes were assigned to their established sub-haplogroups and
interpreted with respect to their phylogenetic and geographic background. This study clearly demonstrates
the benefit of full mtGenomes to increase the resolution of mtDNA sequencing in forensic genetics
The plague of 1630 in Modena (Italy) through the study of parish registers
No full textThe purpose of this paper is to study the impact this disease had on the community in Modena during the epidemic in 1630 and highlight the real course of the disease that brought Modena and whole Europe to its knees in the 17th century. The investigation was carried out by transcribing and studying the parish certificates of death for the period 1625-1635. This study confirmed that the plague epidemic in Modena began as early as 1629, and then exploded in the most virulent form since the beginning of summer 1630 and reached its peak in August of the same year, when it caused about seven hundred victims
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