scholarly journals Reconstructing the history of founder events using genome-wide patterns of allele sharing across individuals

2020 ◽  
Author(s):  
Rémi Tournebize ◽  
Gillian Chu ◽  
Priya Moorjani
Keyword(s):  
Disease Risk ◽  
Sequence Data ◽  
South Asians ◽  
Critical Role ◽  
Allele Sharing ◽  
Ashkenazi Jews ◽  
Island Populations ◽  
Locus Method ◽  
History Of ◽  
Founder Events

AbstractFounder events play a critical role in shaping genetic diversity, impacting the fitness of a species and disease risk in humans. Yet our understanding of the prevalence and distribution of founder events in humans and other species remains incomplete, as most existing methods for characterizing founder events require large sample sizes or phased genomes. To learn about the frequency and evolutionary history of founder events, we introduce ASCEND (Allele Sharing Correlation for the Estimation of Non-equilibrium Demography), a flexible two-locus method to infer the age and strength of founder events. This method uses the correlation in allele sharing across the genome between pairs of individuals to recover signatures of past bottlenecks. By performing coalescent simulations, we show that ASCEND can reliably estimate the parameters of founder events under a range of demographic scenarios, with genotype or sequence data. We apply ASCEND to ~5,000 worldwide human samples (~3,500 present-day and ~1,500 ancient individuals), and ~1,000 domesticated dog samples. In both species, we find pervasive evidence of founder events in the recent past. In humans, over half of the populations surveyed in our study had evidence for a founder events in the past 10,000 years, associated with geographic isolation, modes of sustenance, and historical invasions and epidemics. We document that island populations have historically maintained lower population sizes than continental groups, ancient hunter-gatherers had stronger founder events than Neolithic Farmers or Steppe Pastoralists, and periods of epidemics such as smallpox were accompanied by major population crashes. Many present-day groups--including Central & South Americans, Oceanians and South Asians--have experienced founder events stronger than estimated in Ashkenazi Jews who have high rates of recessive diseases due to their history of founder events. In dogs, we uncovered extreme founder events in most groups, more than ten times stronger than the median strength of founder events in humans. These founder events occurred during the last 25 generations and are likely related to the establishment of dog breeds during Victorian times. Our results highlight a widespread history of founder events in humans and dogs, and provide insights about the demographic and cultural processes underlying these events.

scholarly journals The promise of disease gene discovery in South Asia

2016 ◽  
Author(s):  
Nathan Nakatsuka ◽  
Priya Moorjani ◽  
Niraj Rai ◽  
Biswanath Sarkar ◽  
Arti Tandon ◽  
...  
Keyword(s):  
South Asia ◽  
Disease Burden ◽  
South Asians ◽  
Large Population ◽  
Disease Genes ◽  
Ashkenazi Jews ◽  
Disease Gene Discovery ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Founder Events

The more than 1.5 billion people who live in South Asia are correctly viewed not as a single large population, but as many small endogamous groups. We assembled genome-wide data from over 2,800 individuals from over 260 distinct South Asian groups. We identify 81 unique groups, of which 14 have estimated census sizes of more than a million, that descend from founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events. We identify multiple examples of recessive diseases in South Asia that are the result of such founder events. This study highlights an under-appreciated opportunity for reducing disease burden among South Asians through the discovery of and testing for recessive disease genes.

scholarly journals Secondary findings in inherited heart conditions: a genotype-first feasibility study to assess phenotype, behavioural and psychosocial outcomes

2020 ◽  
Vol 28 (11) ◽  
pp. 1486-1496
Author(s):  
Elizabeth Ormondroyd ◽  
Andrew R. Harper ◽  
Kate L. Thomson ◽  
Michael P. Mackley ◽  
Jennifer Martin ◽  
...  
Keyword(s):  
Family History ◽  
Disease Risk ◽  
Sequence Data ◽  
Healthcare Services ◽  
Secondary Findings ◽  
Participant Satisfaction ◽  
Psychosocial Consequences ◽  
Uncertain Significance ◽  
History Of ◽  
Relevant Family History

Abstract Disclosing secondary findings (SF) from genome sequencing (GS) can alert carriers to disease risk. However, evidence around variant-disease association and consequences of disclosure for individuals and healthcare services is limited. We report on the feasibility of an approach to identification of SF in inherited cardiac conditions (ICC) genes in participants in a rare disease GS study, followed by targeted clinical evaluation. Qualitative methods were used to explore behavioural and psychosocial consequences of disclosure. ICC genes were analysed in genome sequence data from 7203 research participants; a two-stage approach was used to recruit genotype-blind variant carriers and matched controls. Cardiac-focused medical and family history collection and genetic counselling were followed by standard clinical tests, blinded to genotype. Pathogenic ICC variants were identified in 0.61% of individuals; 20 were eligible for the present study. Four variant carriers and seven non-carrier controls participated. One variant carrier had a family history of ICC and was clinically affected; a second was clinically unaffected and had no relevant family history. One variant, in two unrelated participants, was subsequently reclassified as being of uncertain significance. Analysis of qualitative data highlights participant satisfaction with approach, willingness to follow clinical recommendations, but variable outcomes of relatives’ engagement with healthcare services. In conclusion, when offered access to SF, many people choose not to pursue them. For others, disclosure of ICC SF in a specialist setting is valued and of likely clinical utility, and can be expected to identify individuals with, and without a phenotype.

The burden of cardiovascular disease risk factors in the Middle East: A systematic review and meta-analysis focusing on primary prevention

2020 ◽  
Vol 18 ◽  
Author(s):  
Akshaya Srikanth Bhagavathula ◽  
Abdullah Shehab ◽  
Anhar Ullah ◽  
Jamal Rahmani
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Cardiovascular Disease ◽  
Family History ◽  
Primary Prevention ◽  
Middle East ◽  
Disease Risk ◽  
Meta Analysis ◽  
Middle Eastern ◽  
History Of

Background: The increasing incidence of cardiovascular disease (CVD) threatens the Middle Eastern population. Several epidemiological studies have assessed CVD and its risk factors in terms of the primary prevention of CVD in the Middle East. Therefore, summarizing the information from these studies is essential. Aim: We conducted a systematic review to assess the prevalence of CVD and its major risk factors among Middle Eastern adults based on the literature published between January 1, 2012 and December 31, 2018 and carried out a meta-analysis. Methods: We searched electronic databases such as PubMed/Medline, ScienceDirect, Embase and Google Scholar to identify literature published from January 1, 2012 to December 31, 2018. All the original articles that investigated the prevalence of CVD and reported at least one of the following factors were included: hypertension, diabetes, dyslipidaemia, smoking and family history of CVD. To summarize CVD prevalence, we performed a random-effects meta-analysis. Results: A total of 41 potentially relevant articles were included, and 32 were included in the meta-analysis (n=191,979). The overall prevalence of CVD was 10.1% (95% confidence interval (CI): 7.1-14.3%, p<0.001) in the Middle East. A high prevalence of CVD risk factors, such as dyslipidaemia (43.3%; 95% CI: 21.5-68%), hypertension (26.2%; 95% CI: 19.6-34%) and diabetes (16%; 95% CI: 9.9-24.8%), was observed. The prevalence rates of other risk factors, such as smoking (12.4%; 95% CI: 7.7-19.4%) and family history of CVD (18.7%; 95% CI: 15.4-22.5%), were also high. Conclusion: The prevalence of CVD is high (10.1%) in the Middle East. The burden of dyslipidaemia (43.3%) in this region is twice as high as that of hypertension (26.2%) and diabetes mellitus (16%). Multifaceted interventions are urgently needed for the primary prevention of CVD in this region.

Chips with Everything

2017 ◽  
Author(s):  
David Segal
Keyword(s):  
Quantum Computing ◽  
Integrated Circuits ◽  
Critical Role ◽  
Moore’S Law ◽  
Moore's Law ◽  
Silicon Chips ◽  
History Of ◽  
Future Potential ◽  
Digital Computers ◽  
Dna Computer

Chapter 3 highlights the critical role materials have in the development of digital computers. It traces developments from the cat’s whisker to valves through to relays and transistors. Accounts are given for transistors and the manufacture of integrated circuits (silicon chips) by use of photolithography. Future potential computing techniques, namely quantum computing and the DNA computer, are covered. The history of computability and Moore’s Law are discussed.

Friends of Rose Canyon

2018 ◽  
Vol 95 (3) ◽  
pp. 2-20 ◽  
Author(s):  
Andrew Wiese
Keyword(s):  
Open Space ◽  
Critical Role ◽  
First Century ◽  
Grassroots Politics ◽  
History Of ◽  
University City ◽  
Participant Observer ◽  
The Rose

Place-based activism has played a critical role in the history of urban and environmental politics in California. This article explores the continuing significance of environmental place making to grassroots politics through a case study of Friends of Rose Canyon, an environmental group in San Diego. Based in the fast-growing University City neighborhood, Friends of Rose Canyon waged a long, successful campaign between 2002 and 2018 to prevent construction of a bridge in the Rose Canyon Open Space Park in their community. Using historical and participant observer methodologies, this study reveals how twenty-first-century California urbanites claimed and created meaningful local places and mobilized effective politics around them. It illuminates the critical role of individual activists; suggests practical, replicable strategies for community mobilization; and demonstrates the significant impact of local activism at the urban and metropolitan scales.

IMGs Have Played Critical Role In History of U.S. Psychiatry

2002 ◽  
Vol 37 (21) ◽  
pp. 18-44
Author(s):  
David Milne
Keyword(s):  
Critical Role ◽  
History Of

scholarly journals CHEK2∗1100delC Mutation and Risk of Prostate Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Victoria Hale ◽  
Maren Weischer ◽  
Jong Y. Park
Keyword(s):  
Prostate Cancer ◽  
Current Knowledge ◽  
Prostate Cancer Screening ◽  
Critical Role ◽  
Prostate Cancer Risk ◽  
Conclusive Evidence ◽  
Increased Risk ◽  
History Of ◽  
Cancer Studies

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer.CHEK2plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, ofCHEK2on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussedCHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating thatCHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.

scholarly journals Incidence of diabetes in South Asian young adults compared to Pima Indians

2021 ◽  
Vol 9 (1) ◽  
pp. e001988
Author(s):  
K M Venkat Narayan ◽  
Dimple Kondal ◽  
Sayuko Kobes ◽  
Lisa R Staimez ◽  
Deepa Mohan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
South Asians ◽  
Diabetes Incidence ◽  
Pima Indians ◽  
Men And Women ◽  
High Prevalence ◽  
History Of ◽  
Indian Men ◽  
Design And Methods

IntroductionSouth Asians (SA) and Pima Indians have high prevalence of diabetes but differ markedly in body size. We hypothesize that young SA will have higher diabetes incidence than Pima Indians at comparable body mass index (BMI) levels.Research design and methodsWe used prospective cohort data to estimate age-specific, sex, and BMI-specific diabetes incidence in SA aged 20–44 years living in India and Pakistan from the Center for Cardiometabolic Risk Reduction in South Asia Study (n=6676), and compared with Pima Indians, from Pima Indian Study (n=1852).ResultsAt baseline, SA were considerably less obese than Pima Indians (BMI (kg/m2): 24.4 vs 33.8; waist circumference (cm): 82.5 vs 107.0). Age-standardized diabetes incidence (cases/1000 person-years, 95% CI) was lower in SA than in Pima Indians (men: 14.2, 12.2–16.2 vs 37.3, 31.8–42.8; women: 14.8, 13.0–16.5 vs 46.1, 41.2–51.1). Risk of incident diabetes among 20–24-year-old Pima men and women was six times (relative risk (RR), 95% CI: 6.04, 3.30 to 12.0) and seven times (RR, 95% CI: 7.64, 3.73 to 18.2) higher as compared with SA men and women, respectively. In those with BMI <25 kg/m2, however, the risk of diabetes was over five times in SA men than in Pima Indian men. Among those with BMI ≥30 kg/m2, diabetes incidence in SA men was nearly as high as in Pima men. SA and Pima Indians had similar magnitude of association between age, sex, BMI, and insulin secretion with diabetes. The effect of family history was larger in SA, whereas that of insulin resistance was larger in Pima IndiansConclusionsIn the background of relatively low insulin resistance, higher diabetes incidence in SA is driven by poor insulin secretion in SA men. The findings call for research to improve insulin secretion in early natural history of diabetes.

scholarly journals A dark clue to seesaw and leptogenesis in a pseudo-Dirac singlet doublet scenario with (non)standard cosmology

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Partha Konar ◽  
Ananya Mukherjee ◽  
Abhijit Kumar Saha ◽  
Sudipta Show
Keyword(s):  
Dark Matter ◽  
Thermal History ◽  
Direct Detection ◽  
Critical Role ◽  
Mass Term ◽  
Baryon Asymmetry ◽  
Dark Sector ◽  
Lepton Asymmetry ◽  
History Of ◽  
The Universe

Abstract We propose an appealing alternative scenario of leptogenesis assisted by dark sector which leads to the baryon asymmetry of the Universe satisfying all theoretical and experimental constraints. The dark sector carries a non minimal set up of singlet doublet fermionic dark matter extended with copies of a real singlet scalar field. A small Majorana mass term for the singlet dark fermion, in addition to the typical Dirac term, provides the more favourable dark matter of pseudo-Dirac type, capable of escaping the direct search. Such a construction also offers a formidable scope to radiative generation of active neutrino masses. In the presence of a (non)standard thermal history of the Universe, we perform the detailed dark matter phenomenology adopting the suitable benchmark scenarios, consistent with direct detection and neutrino oscillations data. Besides, we have demonstrated that the singlet scalars can go through CP-violating out of equilibrium decay, producing an ample amount of lepton asymmetry. Such an asymmetry then gets converted into the observed baryon asymmetry of the Universe through the non-perturbative sphaleron processes owing to the presence of the alternative cosmological background considered here. Unconventional thermal history of the Universe can thus aspire to lend a critical role both in the context of dark matter as well as in realizing baryogenesis.

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