Ancient genomes reveal origin and rapid trans-Eurasian migration of 7^th century Avar elites

The Avars settled the Carpathian Basin in 567/68 CE, establishing an empire lasting over 200 years. Who they were and where they came from is highly debated. Contemporaries have disagreed about whether they were, as they claimed, the direct successors of the Mongolian Steppe Rouran empire that was destroyed by the Turks in ∼550 CE. Here, we analyze new genome-wide data from 66 pre-Avar and Avar-period Carpathian Basin individuals, including the 8 richest Avar-period burials and further elite sites from Avar’s empire core region. Our results provide support for a rapid long-distance trans-Eurasian migration of Avar-period elites. These individuals carried Northeast Asian ancestry matching the profile of preceding Mongolian Steppe populations, particularly a genome available from the Rouran period. Some of the later elite individuals carried an additional non-local ancestry component broadly matching the steppe, which could point to a later migration or reflect greater genetic diversity within the initial migrant population.- Introduction - Results -- Ancient DNA dataset and quality control -- The genomic structure of the pre-Avar-period population -- The genomic structure of the Avar-period population -- Modeling the eastern steppe ancestry of the elites in the core of the Avar empire -- The heterogeneous ancestry in the regions surrounding the Avar empire’s core - Discussion -- Limitations of the study - Star Method

Magyarországi ikerkutatások: éegy évtized eredményei [Hungarian twin studies: results of four decades]

Twin studies play a role in examining the contribution of genetic variations and environmental factors responsible for the determination of phenotypic variables and of genetic linkage between genotypes. Hungarian twin studies, supported by three twin registries (among them two twin-database), date back to 1970s. Studies mainly focused on various congenital abnormalities, the effect of contraceptive pills and folic acid on the frequency of twin pregnancies, as well as psychosexual and alcohol consumptional behaviors. Monogenic Mendelian inheritance of lactose (mal)absorption was demonstrated for the first time. Hungarian Twin Registry was founded in 2007, which contributed to the current understanding on the background of several disorders, e.g. metabolic syndrome and atherosclerosis. As part of an international twin study, among others, arterial stiffness, central blood pressure, carotid intima/media thickness, venous biomechanics, body composition, lung function and smoking characteristics were also assessed. Absence of genetic background in non-alcoholic fatty liver disease and high inheritance of carotid plaque characteristics were demonstrated for the first time. The review also aims to summarize future plans of the Hungarian Twin Registry. Orv. Hetil., 2013, 154, 1579-1586

A metabolikus szindróma összetevőinek genetikai meghatározottsága: ikervizsgálatok eredményei [Heritability of the risk factors characteristic for the metabolic syndrome: a twin study]

A metabolikus szindrómára jellemző cardiovascularis kockázati tényezők alakulásában örökletes és környezeti tényezők is szerepet kapnak. A genetikai és környezeti tényezők jellegzetességei populációkként változhatnak. Célkitűzés: Az ikervizsgálat célja a metabolikus szindrómában szereplő cardiovascularis kockázati tényezők genetikai, illetve környezeti meghatározottságának megállapítása volt. Módszer: A tanulmányban 101 egészséges felnőtt ikerpár (63 pár monozigóta, 38 pár azonos nemű dizigóta; n = 202, életkor: 43,3±15,8 év) szerepelt. Fizikális vizsgálat után a betegek kérdőívet töltöttek ki, majd éhomi vérvételre került sor. A statisztikai értékelés során a genetikai, a közös és egyéni környezeti determináltság százalékos arányát jelző öröklődési indexek meghatározása történt az A-C-E strukturált egyenletmodell illeszkedése alapján. Az adatok életkorra, nemre (Modell-1), illetve életkorra, nemre, BMI- és haskörfogatértékre korrigáltak (Modell-2). Eredmények: A haskörfogat (illetve a többi antropometriai paraméter [testmagasság, testsúly]) alakulása terén egyértelműen dominált a genetikai meghatározottság (Modell-1-érték: 71,0–88,1%). Kevésbé markánsan voltak az örökletes tényezők a meghatározók a szisztolés és a diasztolés vérnyomásérték alakulására (Modell-2-érték: 57,1% és 57,7%). A Modell-2-érték alapján az egyéni környezeti tényezők játszottak jelentősebb szerepet a szérumtriglicerid értékének (55,9%) alakulásában, míg a közös környezeti determináltság volt a meghatározó a szérum-HDL-koleszterin (58,1%) és az éhomi vércukor (57,1%) értékének alakulásában. A Modell-1- és Modell-2-értékek összehasonlítása arra utalt, hogy az antropometriai paraméterek (BMI, haskörfogat) csak kis hányadban (0,0–17,1%) kaptak szerepet a metabolikus szindróma genetikai és környezeti összetevőinek determináltságában. Következtetések: Felnőtt, magukat egészségesnek tartó egyének körében a metabolikus szindróma komponensei között a genetikai tényezőknek meghatározó szerepe van a haskörfogat és a vérnyomás alakulása terén, míg a szérumtriglicerid-, a HDL-koleszterin- és az éhomi vércukorérték alakulására környezeti tényezők vannak elsősorban befolyással. Az egyes kockázati tényezők eltérő öröklődése kétségessé teszi a metabolikus szindróma eredeti, egységes kóroktanon alapuló koncepciójának helyességét. A vizsgálat eredményei egyéni és társadalmi szinten egyaránt segíthetik a primer cardiovascularis prevenció megtervezését és kivitelezését. Orv. Hetil., 2011, 152, 1265–1271. | Both genetic and environmental factors play role in the pathogenesis of the metabolic syndrome. The magnitude of genetic and environmental influences on the components of metabolic syndrome may vary in different populations. Aims: The present study was aimed to determine the effects of genetic and environmental factors on risk factors characteristic for the metabolic syndrome. Methods: A total of 101 (63 monozygotic and 38 dizygotic) adult twin pairs (n = 202; mean age: 43.3±15.8 years) were investigated. Medical history was recorded and physical examination was carried out for each subject. Fasting venous blood samples were used for measuring laboratory parameters. The presented estimates include the heritability structural equation (A-C-E) model results. In Model-1, all presented parameters are age- and gender- corrected. In Model-2, parameters were corrected for age, gender, body mass index and waist circumference. Results: Heritability in waist circumference (as well as in other anthropometric parameters such as weight and height) was high (Model-1: 71.0–88.1%). Similarly, genetic factors had the highest proportion of total phenotypic variance in systolic and diastolic blood pressure (Model-2: 57.1% and 57.7%, respectively). Based on the results of Model-2, unique environmental factors dominate alterations in serum triglycerides values (55.9%) while shared environmental factors proved to be substantial in alterations of HDL-cholesterol and fasting blood glucose values (58.1% and 57.1%, respectively). Comparing the results of Model-1 and Model-2, the difference in A-C-E model varied from 0.0% to 17.1%, indicating that only a minor proportion of genetic and environmental influences can be explained by the effects of anthropometric parameters. Conclusions: Among adult Hungarian healthy people, genetic factors have substantial influence on waist circumference and blood pressure values while environmental factors dominate alterations in serum triglycerides, HDL-cholesterol and fasting blood glucose values. The different heritability of individual risk factors challenges the original unifying concept of the metabolic syndrome. The results may be useful for establishing and implementing primary cardiovascular prevention both at individual and population levels. Orv. Hetil., 2011, 152, 1265–1271

Leukoencephalopathy, cerebral calcifications and cysts: a family study

We present a clinical, neuro-radiological and genetic study on a family with members suffering from an autosomal dominantly inherited syndrome characterised by epilepsy, cerebral calcifications and cysts, bone abnormalities; progressive neuro-cognitive deterioration and paranasal sinusitis. This syndrome shares several features with leukoencephalopathy with calcifications and cysts also called Labrune syndrome and the condition of cerebroretinal microangiopathy with calcifications and cysts (CRMCC; Coats plus syndrome). Genetic studies in this family did not reveal mutations in the CTC1 gene defected in CRMCC. We interpret our results as those supporting recent findings that despite clinical similarities, late-onset Labrune and Coats plus syndrome might be distinct entities. This family may have Labrune syndrome or a yet unclassified entity; exploration of similar cases could help classifying this one, and related conditions

Genetic impact dominates over environmental effects in development of carotid artery stiffness

Arterial stiffness is an independent predictor of cardiovascular, cerebrovascular and all-cause mortality. Quantifying the genetic influence on the stiff arterial phenotype allows us to better predict the development of arterial stiffness. In this study, we aimed to determine the heritability of carotid artery stiffness in healthy twins. We studied 98 twin pairs of both sexes. We determined carotid artery stiffness locally using echo tracking and applanation tonometry. We estimated the heritability of stiffness parameters using structural equation modeling. The carotid distensibility coefficient showed the highest heritability (64%, 95% confidence interval 45-77%). The incremental elastic modulus, compliance and stiffness index beta also showed substantial heritability (62%, 61% and 58%, respectively). The remaining 36-42% phenotypic variance was attributed to unshared environmental effects. Genetic influence appears to dominate over environmental factors in the development of carotid artery stiffness. Environmental factors may have an important role in favorably influencing the genetic predisposition for accelerated arterial stiffening.Hypertension Research advance online publication, 3 October 2013; doi:10.1038/hr.2013.133

Tight co-twin similarity of monozygotic twins for hTERT protein level of T cell subsets, for telomere length and mitochondrial DNA copy number, but not for telomerase activity.

Our study analyzed lymphocyte subpopulations of 32 monozygotic twins and compared the level of the catalytic reverse transcriptase protein subunit (hTERT) in T lymphocytes (Tly), helper- (Th), cytotoxic- (Tc) and regulatory T cell (Treg) subgroups. Four variables related to telomere and mitochondrial biology were simultaneously assessed, applying multi-parametric flow cytometry, TRAP-ELISA assay and qPCR standard curve method on peripheral blood mononuclear cell (PBMC) samples of genetically matched individuals. Twin data of telomerase activity (TA), hTERT protein level, telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were analyzed for co-twin similarity. The present study has provided novel information by demonstrating very high intraclass correlation (ICC) of hTERT protein level in T lymphocytes (0.891) and in both Th (0.896), Treg (0.885) and Tc (0.798) cell subgroups. When comparing results measured from PBMCs, intraclass correlation was also high for telomere length (0.815) and considerable for mtDNA copy number (0.524), and again exceptionally high for the rate-limiting telomerase subunit, hTERT protein level (0.946). In contrast, telomerase activity showed no co-twin similarity (ICC 0). By comparing relative amounts of hTERT protein levels in different lymphocyte subgroups of twin subjects, in Treg cells significantly higher level could be detected compared to Tly, Th or Tc cell subgroups. This is the first study that simultaneously analyzed co-twin similarity in MZ twins for the above four variables and alongside assessed their relationship, whereby positive association was found between TL and mtDNAcn