1. |
- Speliotes, Elizabeth K., et al.
(author)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Journal article (peer-reviewed)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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2. |
- Wang, Haidong, et al.
(author)
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Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013
- 2014
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 384:9947, s. 957-979
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Journal article (peer-reviewed)abstract
- BACKGROUND: Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29 000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.
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3. |
- Stevens, Kristen N, et al.
(author)
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19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
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Journal article (peer-reviewed)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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4. |
- 't Hart, Leen M., et al.
(author)
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The CTRB1/2 Locus Affects Diabetes Susceptibility and Treatment via the Incretin Pathway
- 2013
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:9, s. 3275-3281
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Journal article (peer-reviewed)abstract
- The incretin hormone glucagon-like peptide 1 (GLP-1) promotes glucose homeostasis and enhances -cell function. GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which inhibit the physiological inactivation of endogenous GLP-1, are used for the treatment of type 2 diabetes. Using the Metabochip, we identified three novel genetic loci with large effects (30-40%) on GLP-1-stimulated insulin secretion during hyperglycemic clamps in nondiabetic Caucasian individuals (TMEM114; CHST3 and CTRB1/2; n = 232; all P 8.8 x 10(-7)). rs7202877 near CTRB1/2, a known diabetes risk locus, also associated with an absolute 0.51 +/- 0.16% (5.6 +/- 1.7 mmol/mol) lower A1C response to DPP-4 inhibitor treatment in G-allele carriers, but there was no effect on GLP-1 RA treatment in type 2 diabetic patients (n = 527). Furthermore, in pancreatic tissue, we show that rs7202877 acts as expression quantitative trait locus for CTRB1 and CTRB2, encoding chymotrypsinogen, and increases fecal chymotrypsin activity in healthy carriers. Chymotrypsin is one of the most abundant digestive enzymes in the gut where it cleaves food proteins into smaller peptide fragments. Our data identify chymotrypsin in the regulation of the incretin pathway, development of diabetes, and response to DPP-4 inhibitor treatment.
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5. |
- Tinetti, Giovanna, et al.
(author)
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The science of EChO
- 2010
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In: Proceedings of the International Astronomical Union. - 1743-9213 .- 1743-9221. ; 6:S276, s. 359-370
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Journal article (peer-reviewed)abstract
- The science of extra-solar planets is one of the most rapidly changing areas of astrophysics and since 1995 the number of planets known has increased by almost two orders of magnitude. A combination of ground-based surveys and dedicated space missions has resulted in 560-plus planets being detected, and over 1200 that await confirmation. NASA's Kepler mission has opened up the possibility of discovering Earth-like planets in the habitable zone around some of the 100,000 stars it is surveying during its 3 to 4-year lifetime. The new ESA's Gaia mission is expected to discover thousands of new planets around stars within 200 parsecs of the Sun. The key challenge now is moving on from discovery, important though that remains, to characterisation: what are these planets actually like, and why are they as they are In the past ten years, we have learned how to obtain the first spectra of exoplanets using transit transmission and emission spectroscopy. With the high stability of Spitzer, Hubble, and large ground-based telescopes the spectra of bright close-in massive planets can be obtained and species like water vapour, methane, carbon monoxide and dioxide have been detected. With transit science came the first tangible remote sensing of these planetary bodies and so one can start to extrapolate from what has been learnt from Solar System probes to what one might plan to learn about their faraway siblings. As we learn more about the atmospheres, surfaces and near-surfaces of these remote bodies, we will begin to build up a clearer picture of their construction, history and suitability for life. The Exoplanet Characterisation Observatory, EChO, will be the first dedicated mission to investigate the physics and chemistry of Exoplanetary Atmospheres. By characterising spectroscopically more bodies in different environments we will take detailed planetology out of the Solar System and into the Galaxy as a whole. EChO has now been selected by the European Space Agency to be assessed as one of four M3 mission candidates. © International Astronomical Union 2011.
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6. |
- Purrington, Kristen S., et al.
(author)
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Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
- 2014
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:5, s. 1012-1019
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Journal article (peer-reviewed)abstract
- In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
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7. |
- Arridge, Christopher S., et al.
(author)
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Uranus Pathfinder : exploring the origins and evolution of Ice Giant planets
- 2012
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In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 753-791
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Journal article (peer-reviewed)abstract
- The "Ice Giants" Uranus and Neptune are a different class of planet compared to Jupiter and Saturn. Studying these objects is important for furthering our understanding of the formation and evolution of the planets, and unravelling the fundamental physical and chemical processes in the Solar System. The importance of filling these gaps in our knowledge of the Solar System is particularly acute when trying to apply our understanding to the numerous planetary systems that have been discovered around other stars. The Uranus Pathfinder (UP) mission thus represents the quintessential aspects of the objectives of the European planetary community as expressed in ESA's Cosmic Vision 2015-2025. UP was proposed to the European Space Agency's M3 call for medium-class missions in 2010 and proposed to be the first orbiter of an Ice Giant planet. As the most accessible Ice Giant within the M-class mission envelope Uranus was identified as the mission target. Although not selected for this call the UP mission concept provides a baseline framework for the exploration of Uranus with existing low-cost platforms and underlines the need to develop power sources suitable for the outer Solar System. The UP science case is based around exploring the origins, evolution, and processes at work in Ice Giant planetary systems. Three broad themes were identified: (1) Uranus as an Ice Giant, (2) An Ice Giant planetary system, and (3) An asymmetric magnetosphere. Due to the long interplanetary transfer from Earth to Uranus a significant cruise-phase science theme was also developed. The UP mission concept calls for the use of a Mars Express/Rosetta-type platform to launch on a Soyuz-Fregat in 2021 and entering into an eccentric polar orbit around Uranus in the 2036-2037 timeframe. The science payload has a strong heritage in Europe and beyond and requires no significant technology developments.
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11. |
- Liu, Li, et al.
(author)
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New Progress in VLBI tracking of GNSS satellites at GFZ
- 2014
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In: IVS 2014 General Meeting Proceedings "VGOS: The New VLBI Network", Edited by Dirk Behrend, Karen D. Baver, and Kyla L. Armstrong, Science Press (Beijing). - 9787030429742 ; , s. 456-460
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Conference paper (other academic/artistic)
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12. |
- Agmon-Levin, Nancy, et al.
(author)
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International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies
- 2014
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 73:1, s. 17-23
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Journal article (peer-reviewed)abstract
- Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.
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13. |
- Birkeland, Kare I., et al.
(author)
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Insulin degludec in type 1 diabetes : a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine
- 2011
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 34:3, s. 661-665
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.RESEARCH DESIGN AND METHODS: In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m(2)) received subcutaneous injections of IDeg(A) (600 mu mol/L; n = 59), IDeg(B) (900 mu mol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes.RESULTS: At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 +/- 0.8%), IDeg(B) (8.0 +/- 1.0%), and IGlar (7.6 +/- 0.8%), as was FPG (8.3 +/- 4.0, 8.3 +/- 2.8, and 8.9 +/- 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52-1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65-1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25-0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44-1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.CONCLUSIONS: In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.
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14. |
- Dilday, Benjamin, et al.
(author)
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A Measurement of the Rate of Type Ia Supernovae in Galaxy Clusters from the SDSS-II Supernova Survey
- 2010
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 715, s. 1021-1035
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Journal article (peer-reviewed)abstract
- We present measurements of the Type Ia supernova (SN) rate in galaxy clusters based on data from the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey. The cluster SN Ia rate is determined from 9 SN events in a set of 71 C4 clusters at z <= 0.17 and 27 SN events in 492 maxBCG clusters at 0.1 <= z <= 0.3. We find values for the cluster SN Ia rate of (0.37+0.17+0.01 -0.12-0.01) SNur h 2 and (0.55+0.13+0.02 -0.11-0.01) SNur h 2 (SNux = 10-12 L -1 xsun yr-1) in C4 and maxBCG clusters, respectively, where the quoted errors are statistical and systematic, respectively. The SN rate for early-type galaxies is found to be (0.31+0.18+0.01 -0.12-0.01) SNur h 2 and (0.49+0.15+0.02 -0.11-0.01) SNur h 2 in C4 and maxBCG clusters, respectively. The SN rate for the brightest cluster galaxies (BCG) is found to be (2.04+1.99+0.07 -1.11-0.04) SNur h 2 and (0.36+0.84+0.01 -0.30-0.01) SNur h 2 in C4 and maxBCG clusters, respectively. The ratio of the SN Ia rate in cluster early-type galaxies to that of the SN Ia rate in field early-type galaxies is 1.94+1.31+0.043 -0.91-0.015 and 3.02+1.31+0.062 -1.03-0.048, for C4 and maxBCG clusters, respectively. The SN rate in galaxy clusters as a function of redshift, which probes the late time SN Ia delay distribution, shows only weak dependence on redshift. Combining our current measurements with previous measurements, we fit the cluster SN Ia rate data to a linear function of redshift, and find rL = [(0.49+0.15 -0.14)+(0.91+0.85 -0.81) × z] SNuB h 2. A comparison of the radial distribution of SNe in cluster to field early-type galaxies shows possible evidence for an enhancement of the SN rate in the cores of cluster early-type galaxies. With an observation of at most three hostless, intra-cluster SNe Ia, we estimate the fraction of cluster SNe that are hostless to be (9.4+8.3 -5.1)%.
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15. |
- Dilday, Benjamin, et al.
(author)
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Measurements of the Rate of Type Ia Supernovae at Redshift lsim0.3 from the Sloan Digital Sky Survey II Supernova Survey
- 2010
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 713, s. 1026-1036
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Journal article (peer-reviewed)abstract
- We present a measurement of the volumetric Type Ia supernova (SN Ia) rate based on data from the Sloan Digital Sky Survey II (SDSS-II) Supernova Survey. The adopted sample of supernovae (SNe) includes 516 SNe Ia at redshift z <~ 0.3, of which 270(52%) are spectroscopically identified as SNe Ia. The remaining 246 SNe Ia were identified through their light curves; 113 of these objects have spectroscopic redshifts from spectra of their host galaxy, and 133 have photometric redshifts estimated from the SN light curves. Based on consideration of 87 spectroscopically confirmed non-Ia SNe discovered by the SDSS-II SN Survey, we estimate that 2.04+1.61 -0.95% of the photometric SNe Ia may be misidentified. The sample of SNe Ia used in this measurement represents an order of magnitude increase in the statistics for SN Ia rate measurements in the redshift range covered by the SDSS-II Supernova Survey. If we assume an SN Ia rate that is constant at low redshift (z < 0.15), then the SN observations can be used to infer a value of the SN rate of rV = (2.69+0.34+0.21 -0.30-0.01)×10-5 SNe yr-1 Mpc-3 (H 0/(70 km s-1 Mpc-1))3 at a mean redshift of ~0.12, based on 79 SNe Ia of which 72 are spectroscopically confirmed. However, the large sample of SNe Ia included in this study allows us to place constraints on the redshift dependence of the SN Ia rate based on the SDSS-II Supernova Survey data alone. Fitting a power-law model of the SN rate evolution, rV (z) = Ap × ((1 + z)/(1 + z 0))ν, over the redshift range 0.0 < z < 0.3 with z 0 = 0.21, results in Ap = (3.43+0.15 -0.15) × 10-5 SNe yr-1 Mpc-3 (H 0/(70 km s-1 Mpc-1))3 and ν = 2.04+0.90 -0.89.
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16. |
- Iovino, Mariangela, et al.
(author)
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The novel MAPT mutation K298E: mechanisms of mutant tau toxicity, brain pathology and tau expression in induced fibroblast-derived neurons
- 2014
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In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 127:2, s. 283-295
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Journal article (peer-reviewed)abstract
- Frontotemporal lobar degeneration (FTLD) consists of a group of neurodegenerative diseases characterized by behavioural and executive impairment, language disorders and motor dysfunction. About 20-30 % of cases are inherited in a dominant manner. Mutations in the microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T). Here we report a novel MAPT mutation (K298E) in exon 10 in a patient with FTDP-17T. Neuropathological studies of post-mortem brain showed widespread neuronal loss and gliosis and abundant deposition of hyperphosphorylated tau in neurons and glia. Molecular studies demonstrated that the K298E mutation affects both protein function and alternative mRNA splicing. Fibroblasts from a skin biopsy of the proband taken at post-mortem were directly induced into neurons (iNs) and expressed both 3-repeat and 4-repeat tau isoforms. As well as contributing new knowledge on MAPT mutations in FTDP-17T, this is the first example of the successful generation of iNs from skin cells retrieved post-mortem.
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18. |
- Väli, Ülo, et al.
(author)
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Widespread hybridization between the Greater Spotted Eagle Aquila clanga and the Lesser Spotted Eagle Aquila pomarina (Aves: Accipitriformes) in Europe
- 2010
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In: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 100:3, s. 725-736
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Journal article (peer-reviewed)abstract
- Hybridization is a significant threat for endangered species and could potentially even lead to their extinction. This concern applies to the globally vulnerable Greater Spotted Eagle Aquila clanga, a species that co-occurs, and potentially interbreeds, with the more common Lesser Spotted Eagle Aquila pomarina in a vast area of Eastern Europe. We applied single nucleotide polymorphism (SNP) and microsatellite markers in order to study hybridization and introgression in 14 European spotted eagle populations. We detected hybridization and/or introgression in all studied sympatric populations. In most regions, hybridization took place prevalently between A. pomarina males and A. clanga females, with introgression to the more common A. pomarina. However, such a pattern was not as obvious in regions where A. clanga is still numerous. In the course of 16 years of genetic monitoring of a mixed population in Estonia, we observed the abandonment of A. clanga breeding territories and the replacement of A. clanga pairs by A. pomarina, whereby on several occasions hybridization was an intermediate step before the disappearance of A. clanga. Although the total number of Estonian A. clanga × A. pomarina pairs was twice as high as that of A. clanga pairs, the number of pairs recorded yearly were approximately equal, which suggests a higher turnover rate in interbreeding pairs. This study shows that interspecific introgressive hybridization occurs rather frequently in a hybrid zone at least 1700-km wide: it poses an additional threat for the vulnerable A. clanga, and may contribute to the extinction of its populations.
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