Y chromosome variation in Europe: Continental and local processes in the formation of the extant gene pool

The polymorphism of the male-specific portion of the Y chromosome has been increasingly used to describe the composition of the European gene pool and to reconstruct its formation. Here the theoretical grounds and the limitations of this approach are presented, together with the different views on debated issues. The emerging picture for the composition of the male gene pool of the continent is illustrated, but local peculiarities that represent departures from the main trends are also highlighted, in order to illustrate the main unifying feature, i.e. the overlay of recent patterns onto more ancient ones. A synopsis of the main findings and conclusions obtained in regional studies has also been compiled. © 2007 Informa UK Ltd

SSADH variation in primates: Intra- and interspecific data on a gene with a potential role in human cognitive functions

In the present study we focus on the nucleotide and the inferred amino acid variation occurring in humans and other primate species for mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase, a gene recently supposed to contribute to cognitive performance in humans. We determined 2527 bp of coding, intronic, and flanking sequences from chimpanzee, bonobo, gorilla, orangutan, gibbon, and macaque. We also resequenced the entire coding sequence on 39 independent chromosomes from Italian families. Four variable coding sites were genotyped in additional populations from Europe, Africa, and Asia. A test for constancy of the nonsynonymous vs. synonymous rates of nucleotide changes revealed that primates are characterized by largely variable d(N)/d(S) ratios. On a background of strong conservation, probably controlled by selective constraints, the lineage leading to humans showed a ratio increased to 0.42. Human polymorphic levels fall in the range reported for other genes, with a pattern of frequency and haplotype structure strongly suggestive of nonneutrality. The comparison with the primate sequences allowed inferring the ancestral state at all variable positions, suggesting that the c.538(C) allele and the associated functional variant is indeed a derived state that is proceeding to fixation. The unexpected pattern of human polymorphism compared to interspecific findings outlines the possibility of a recent positive selection on some variants relevant to new cognitive capabilities unique to humans

Y-chromosomal variation in the Czech Republic

To analyze the contribution of the Czech population to the Y-chromosome diversity landscape of Europe and to reconstruct past demographic events, we typed 257 males from five locations for 21 UEPs. Moreover, 141 carriers of the three most common haplogroups were typed for 10 microsatellites and coalescent analyses applied. Sixteen Hg's characterized by derived alleles were identified, the most common being R1a-SRY10831 and P-DYS257*(xR1a). The pool of haplogroups within I-M170 represented the third most common clade. Overall, the degree of population structure was low. The ages for Hg I-M170, P-DYS257*(xR1a), and R1a-SRY10831 appeared to be comparable and compatible with their presence during or soon after the LGM. A signal of population growth beginning in the first millennium B.C. was detected. Its similarity among the three most common Hg's indicated that growth was characteristic for a gene pool that already contained all of them. The Czech population appears to be influenced, to a very moderate extent, by genetic inputs from outside Europe in the post-Neolithic and historical times. Population growth postdated the archaeologically documented introduction of Neolithic technology and the estimated central value coincides with a period of repeated changes driven by the development of metal technologies and the associated social and trade organization

Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency

Succinate semialdehyde dehydrogenase (SSADH; ALlDH5A1) deficiency, a rare metabolic disorder that disrupts the normal degradation of GABA, gives rise to a highly heterogeneous neurological phenotype ranging from mild to very severe. The nature of the mutation has so far been reported in patients from six families world wide and eight different mutations were described. Here we report the mutational spectrum in 48 additional unrelated families of different geographic origin. We detected 27 novel mutations at the cDNA level, of which 26 could be attributed to changes at the genomic level. Furthermore, six mutations were detected that did not strongly affect SSADH activity when expressed in HEK 293 cells and are considered nonpathogenic allelic variants. Twenty of the mutations were only found in one family. The spectrum of disease-causing mutations from all patients sequenced thus far consists of 25 point mutations, four small insertions, and five small deletions. Seven of these mutations affect splice junctions, seven are nonsense mutations, and 12 are missense mutations. Although there were no mutational hotspots or prevalent mutations responsible for a significant number of cases, 14 out of 37 (38%) of the missense alleles were present in exon 4 or 5. With one exception, the missense mutations we consider to be causative of SSADH deficiency reduced the SSADH activity to less than 5% of the normal activity in our in vitro expression system. This indicates that residual expression is not likely to be an important factor contributing to the large phenotypic differences observed among different families and even among siblings, suggesting that other modifying factors are of great importance in disease pathology. (C) 2003 Wiley,Liss, Inc

Characterization of prevalence and genetic subtypes of Blastocystis sp. in wild and domestic Suidae of central Italy aided by amplicon NGS

Blastocystis spp. is a common single-celled intestinal symbiont, comprising several genetic subtypes (ST) and trans- missible by animal-to-animal, human-to-human, animal-to-human and, possibly, human-to-animal routes. This work was designed to explore the presence of Blastocystis in sympatric domestic and wild suids and their ability to carry zoonotic STs, in a condition of widespread opportunity to come in contact with the microorganism through their shared water and food resources, and other carriers. We sampled 42 and 37 stool samples from wild boars and domestic pigs, respectively. STs were first identified by PCR followed by Sanger sequencing. Sequences represented in double-band PCR products or in Sanger chromatograms displaying multiple peaks, were resolved by next generation sequencing (NGS). Twenty-six (61.9%) wild boar and 26 (70.2%) pig samples were PCR-positive, respectively. ST3, ST5 and ST15 were found in 3.8%, 38.4% and 80.8% of the positive wild boars and 11.5%, 88.5%, 11.5% of the positive pigs, respectively. ST1 was found only in pigs (3.8%). STs 5 and 15 were common in both groups of animals, but in reversed proportions, suggesting preferential colonization. We found significantly different ST distributions among wild boars and domestic pigs. This might indicate that lifestyle differences between the two populations influence their risk for contracting certain subtypes, or that ST5 and ST15 can colonize preferentially wild or domestic animals. Based on the STs described here, wild boars and domestic pigs can act as reservoirs with zoonotic potential. The ability of suids to carry zoonotic STs appears to be higher when using NGS than Sanger sequencing, and resolution of complex sequencing profiles is imperative before excluding the presence of STs of human concern

Genetic aspects underlying the normocalcemic and hypercalcemic phenotypes of primary hyperparathyroidism

purpose: hypercalcemic primary hyperparathyroidism (PHPT) is a common endocrine disorder that has been very well characterized. In contrast, many aspects of normocalcemic primary hyperparathyroidism (NPHPT) such as natural history, organ damage, and management are still matter of debate. In addition, both the pathophysiology and molecular basis of NPHPT are unclear. we investigated whether PHPT and NPHPT patient cohorts share the same pattern of genetic variation in genes known to be involved in calcium and/or bone metabolism. Research design and methods: Genotyping for 9 single nucleotide polymorphisms (SNPs) was performed by Real-Time PCR (TaqMan assays) on 27 NPHPT and 31 PHPT patients evaluated in a tertiary referral center. the data of both groups were compared with 54 in house-controls and 503 subjects from the 1,000 genomes Project. All groups were compared for allele/haplotype frequencies, on a single locus, two loci and multi-locus basis. Results: The NPHPT group differed significantly at SNPs in OPG and ESR1. also, the NPHPT cohort was peculiar for pairwise associations of genotypes and for the overrepresentation of unusual multilocus genotypes. Conclusions: Our NPHPT patient set harboured a definitely larger quota of genetic diversity than the other samples. Specific genotypes may help in defining subgroups of NPHPT patients which deserve ad hoc clinical and follow-up studies

The peopling of the last Green Sahara revealed by high-coverage resequencing of trans-Saharan patrilineages

Little is known about the peopling of the Sahara during the Holocene climatic optimum, when the desert was replaced by a fertile environment

Whole mitochondrial genome sequencing provides new insights into the phylogeography of loggerhead turtles (Caretta caretta) in the Mediterranean Sea

Population structure and phylogeography of the loggerhead sea turtle (Caretta caretta) have so far been assessed mainly by mitochondrial DNA (mtDNA) single-gene sequencing studies. However, phylogenetic relationships amongst matrilines, genetic characterisation of rookeries and mixed-stock analyses have suffered from the limited resolution obtained by comparison of relatively short sequences such as from the mtDNA control region. Whole mitogenome sequencing can significantly improve population genetics, particularly in marine organisms showing female natal philopatry. Despite mitogenomics becoming increasingly common in biodiversity monitoring and conservation, only a few complete mitogenomes are available for C. caretta. In this study, we sequenced the complete mtDNA of 61 loggerhead turtles sampled between 2008 and 2021 along the Italian coastline and central Mediterranean Sea. We assigned complete mtDNA haplotypes to dead embryos and bycatch samples, and introduced a first nomenclature for loggerhead mitogenomes. Analysis of mtDNA diversity, Maximum Parsimony and Bayesian phylogenetic reconstruction allowed improved resolution of lineages with respect to studies reporting on partial mtDNA control region sequence comparisons, and we were able to further inform previous analyses on loggerhead ancestry based on control region haplogroups. Overall, whole mitogenome analysis has potential for considerable improvement of evolutionary history and phylogeographic investigations as well as mixed-stock surveys of loggerhead turtles

A multistep process for the dispersal of a Y chromosomal lineage in the Mediterranean area

Tn this work we focus on a microsatellite-defined Y-chromosomal lineage (network 1.2) identified by us and reported in previous studies, whose geographic distribution and antiquity appear to be compatible with the Neolithic spread of farmers. Here, we set network 1.2 in the Y-chromosomal phylogenetic tree, date it with respect to other lineages associated with the same movements by other authors, examine its diversity by means of tri- and tetranucleotide loci and discuss the implications hi reconstructing the spread of this group of chromosomes in the Mediterranean area. Our results define a tripartite phylogeny wit-bin HG 9 (Rosser et al. 2000) with the deepest branching defined by alleles T (Haplogroup Eu 10) or G (Haplogroup Eu9) at M172 (Semino et al. 2000), and a subsequent branching within Eu9 defined by network 1.2. Population distributions of HG 9 and network 1.2 show that their occurrence in the surveyed area is not due to the spread of people from a single parental population but, rather, to a process punctuated by at least two phases. Our data identify the wide area of the Balkans, Aegean and Anatolia as the possible homeland harbouring the largest variation within network 1.2. The use of recently proposed tests based on the stepwise mutation model suggests that its spread was associated to a population expansion, xvith a high rate of male gene flow in the Turkish Greek area

Patterns of male-specific inter-population divergence in Europe, West Asia and North Africa

We typed 1801 males from 55 locations for the Y-specific binary markers YAP! DYZ3, SRY10831 and the (CA)n microsatellites YCAII and DYS413. Phylogenetic relationships of chromosomes with the same binary haplotype were condensed in seven large one-step networks! which accounted for 95% of all chromosomes. Their coalescence ages were estimated based on microsatellite diversity. The three largest and oldest networks undergo sharp frequency changes in three areas. The more recent network; 3.1A clearly discriminates between Western and Eastern European populations. Pairwise Pst showed an overall increment with increasing geographic distance but with a slope greatly reduced when compared to previous reports. BI sectioning the entire data set according to geographic and linguistic criteria, we found higher Fst-on-distance slopes within Europe than in West Asia or across the tno continents