Project description:Takabuti, was a female who lived in ancient Egypt during the 25th Dynasty, c.660 BCE. Her mummified remains were brought to Belfast, Northern Ireland, in 1834 and are currently displayed in the Ulster Museum. To gain insight into Takabuti's ancestry, we used deep sampling of vertebral bone, under X-ray control, to obtain non-contaminated bone tissue from which we extracted ancient DNA (aDNA) using established protocols. We targeted the maternally inherited mitochondrial DNA (mtDNA), known to be highly informative for human ancestry, and identified 38 single nucleotide variants using next generation sequencing. The specific combination of these SNVs suggests that Takabuti belonged to mitochondrial haplogroup H4a1. Neither H4 nor H4a1 have been reported in ancient Egyptian samples, prior to this study. The modern distribution of H4a1 is rare and sporadic and has been identified in areas including the Canary Islands, southern Iberia and the Lebanon. H4a1 has also been reported in ancient samples from Bell Beaker and Unetice contexts in Germany, as well as Bronze Age Bulgaria. We believe that this is an important finding because first, it adds to the depth of knowledge about the distribution of the H4a1 haplogroup in existing mtDNA, thus creating a baseline for future occurrences of this haplogroup in ancient Egyptian remains. Second, it is of great importance for archaeological sciences, since a predominantly European haplogroup has been identified in an Egyptian individual in Southern Egypt, prior to the Roman and Greek influx (332BCE).
Project description:Palaeoproteomic study of mummified human skin using a non-destructive sampling technique, based on mixed-bed chromatographic media stabilised on ethylene vinyl acetate membranes (“EVA”), which had previously been used exclusively on historical material, was successful in extracting ancient proteins from the surface of Ancient Egyptian mummies. We tested the method on a decontextualised fragment of skin and assessed the endogeneity of its metaproteome by comparison with a procedural blank. Furthermore, we retrieved and authenticated sequences of collagen and keratin from the mummy of a young woman (Supp. 16747 of the Museum of Anthropology and Ethnography of the University of Turin) who lived and died between 2400 and 2200 BC, during the Old Kingdom of Egypt.
Project description:Rapid advances in biochemical technologies have enabled several strategies for typing candidate HLA alleles, but linking them into a single MHC haplotype structure remains challenging. Here we have developed a multi-loci haplotype phasing technique and demonstrate its utility towards phasing of MHC and KIR loci in human samples. We accurately (~99%) reconstruct the complete haplotypes for over 90% of sequence variants spanning the 4-megabase region of these two loci. By haplotyping a majority of coding and non-coding alleles at the MHC and KIR loci in a single assay, this method has the potential to assist transplantation matching and facilitate investigation of the genetic basis of human immunity and disease. Complete haplotype phasing of 2 loci (MHC and KIR) in 1 human cell line.
Project description:Genitopatellar syndrome (GPS) is mainly characterized by an absence of patellae, congenital flexion contractures of the lower limbs, psychomotor retardation, and anomalies of the external genitalia and kidneys. We report an 18-year-old female with a novel heterozygous truncating mutation in exon 17 of the KAT6B gene [MC_000010.11:c.3603_3606 del, p.Arg1201fs]. This is the first report of typical GPS in a Japanese individual. The details of our findings may contribute to elucidating the mechanism underlying GPS-specific clinical features.
Project description:Rapid advances in biochemical technologies have enabled several strategies for typing candidate HLA alleles, but linking them into a single MHC haplotype structure remains challenging. Here we have developed a multi-loci haplotype phasing technique and demonstrate its utility towards phasing of MHC and KIR loci in human samples. We accurately (~99%) reconstruct the complete haplotypes for over 90% of sequence variants spanning the 4-megabase region of these two loci. By haplotyping a majority of coding and non-coding alleles at the MHC and KIR loci in a single assay, this method has the potential to assist transplantation matching and facilitate investigation of the genetic basis of human immunity and disease.
Project description:The dynamics of ecosystem collapse are fundamental to determining how and why biological communities change through time, as well as the potential effects of extinctions on ecosystems. Here, we integrate depictions of mammals from Egyptian antiquity with direct lines of paleontological and archeological evidence to infer local extinctions and community dynamics over a 6,000-y span. The unprecedented temporal resolution of this dataset enables examination of how the tandem effects of human population growth and climate change can disrupt mammalian communities. We show that the extinctions of mammals in Egypt were nonrandom and that destabilizing changes in community composition coincided with abrupt aridification events and the attendant collapses of some complex societies. We also show that the roles of species in a community can change over time and that persistence is predicted by measures of species sensitivity, a function of local dynamic stability. To our knowledge, our study is the first high-resolution analysis of the ecological impacts of environmental change on predator-prey networks over millennial timescales and sheds light on the historical events that have shaped modern animal communities.
Project description:Prenatal intervention of severe fetal aortic valve stenosis by ultrasound-guided percutaneous balloon valvuloplasty has been performed to prevent the progression to hypoplastic left heart syndrome, and achieve biventricular circulation in neonates. Here we report a case of fetal aortic valvuloplasty prenatally diagnosed with aortic stenosis at 24 weeks of gestation and showed worsening features on a follow-up echocardiography. Prenatal aortic valvuloplasty was performed at 29 weeks of gestation, and was a technical success. However, fetal bradycardia sustained, and an emergency cesarean delivery was performed. To the best of our knowledge, this is the first reported case of fetal aortic valvuloplasty which was performed in Asia.
Project description:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic disorder characterized by fatty degeneration of the right ventricular myocardium with variable involvement of the left ventricle. The condition is associated with exercise-mediated ventricular tachycardia and is one of the recognized causes of sudden cardiac death in the young and in athletes. Here, we report the first confirmed case of ARVC in Oman and present its electrocardiographic, echocardiographic features, and radiological findings on gated, contrast-enhanced cardiac computed tomography. Our patient was a 22-year-old male who had presented to our hospital for evaluation and investigation of syncope and symptomatic palpitations.
Project description:Renal leiomyosarcomas (LMS) are extremely rare neoplasms with aggressive behaviour and poor survival prognosis. The most frequent somatic events in leiomyosarcomas are mutations in TP53, RB1, ATRX and PTEN genes, chromosomal instability and chromoanagenesis. By using chromosomal microarray analysis we identified monosomy of chromosomes 3 and 11, gain of Xp (ATRX) arm and three chromoanasynthesis regions (6q21-q27, 7p22.3-p12.1 and 12q13.11-q21.2), with MDM2 and CDK4 oncogenes copy number gains, whereas no CNVs or tumor specific SNVs in TP53, RB1 and PTEN genes were observed.
Project description:In recent years, there has been an increasing interest in using common single-nucleotide polymorphisms (SNPs) amassed in genome-wide association studies to investigate rare haplotype effects on complex diseases. Evidence has suggested that rare haplotypes may tag rare causal single-nucleotide variants, making SNP-based rare haplotype analysis not only cost effective, but also more valuable for detecting causal variants. Although a number of methods for detecting rare haplotype association have been proposed in recent years, they are population based and thus susceptible to population stratification.We propose family-triad-based logistic Bayesian Lasso (famLBL) for estimating effects of haplotypes on complex diseases using SNP data. By choosing appropriate prior distribution, effect sizes of unassociated haplotypes can be shrunk toward zero, allowing for more precise estimation of associated haplotypes, especially those that are rare, thereby achieving greater detection power. We evaluate famLBL using simulation to gauge its type I error and power. Compared with its population counterpart, LBL, highlights famLBL's robustness property in the presence of population substructure. Further investigation by comparing famLBL with Family-Based Association Test (FBAT) reveals its advantage for detecting rare haplotype association.famLBL is implemented as an R-package available at http://www.stat.osu.edu/?statgen/SOFTWARE/LBL/.