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German Genealogy in Its Social and Political Context
Abstract
In 1933, Hitler's coalition government enacted the "Law for the Restoration of the Professional Civil Service" and the "Reich Law against the Overcrowding of German Schools and Universities" , both laws aimed at the professional exclusion of Jews. Mentally, these laws had been prepared for decades. The book shows how anti-Semitism first and foremost affected academic youth.The associations of German genealogists kept their distance from anti-Semitic endeavors until 1932, with the exception of the "German Roland". However, the proof of ancestry required by the state from 1933 onwards brought a unique boost in employment for the genealogists and a growing interest in family history. By the example of the associations "Roland" (Dresden) a complex picture of mental resistance or factual work up to the miserable hanger-on is drawn from the sources. With consequences reaching far beyond the year 1945.
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Eigentümlich frei Nr. 54 (2005)
Der erweiterte SächsArchReport ist erschienen im Arnshaugk Verlag 2019
Polygenic risk scores (PRS) have become the standard for quantifying genetic liability in the prediction of disease risks. PRSs are generally constructed as weighted sum scores of risk alleles using effect sizes from genome-wide association studies as their weights. The construction of PRSs is being improved with more appropriate selection of independent single nucleotide polymorphisms (SNPs) and optimized estimation of their weights, but is rarely reflected upon from a theoretical perspective, focusing on the validity of the risk score. Borrowing from psychometrics, this paper discusses the validity of PRSs and introduces the three main types of validity that are considered in the evaluation of tests and measurements: construct, content, and criterion validity. This introduction is followed by a discussion of three topics that challenge the validity of PRS, namely their claimed independence of clinical risk factors, the consequences of relaxing SNP inclusion thresholds, and the selection of SNP weights. This discussion of the validity of PRS reminds that we need to keep questioning if weighted sums of risk alleles are measuring what we think they are in the various scenarios in which PRSs are used and that we need to keep exploring alternative modeling strategies that might better reflect the underlying biological pathways.
About 10 years ago, after the first large-scale genome-wide association studies (GWAS) were conducted to find genes associated with common complex diseases, investigators were surprised to find that the amount of heritability explained by the significant hits was very low for almost all the studied traits. Indeed, when compared to heritability estimates expected from the observed trait concordance within families, the heritability explained by the associated variants was always much smaller, more than ten times smaller for some traits. There was thus a problem of “missing heritability” and different hypotheses were proposed to help find this “missing heritability”. These hypotheses involved novel research strategies in which different groups engaged including among others increasing sample sizes of GWAS or looking for rare variants and structural variations that were not captured by the SNP-chips used in GWAS. How successful have these efforts been in finding the “missing heritability”? Could it be that the problem of “missing heritability” was ill-defined? These are the questions that will be addressed in this paper by taking some different examples of complex traits.
Sequences encoding Olduvai (DUF1220) protein domains show the largest human-specific increase in copy number of any coding region in the genome and have been linked to human brain evolution. Most human-specific copies of Olduvai (119/165) are encoded by three NBPF genes that are adjacent to three human-specific NOTCH2NL genes that have been shown to promote cortical neurogenesis. Here, employing genomic, phylogenetic, and transcriptomic evidence, we show that these NOTCH2NL/NBPF gene pairs evolved jointly, as two-gene units, very recently in human evolution, and are likely co-regulated. Remarkably, while three NOTCH2NL paralogs were added, adjacent Olduvai sequences hyper-amplified, adding 119 human-specific copies. The data suggest that human-specific Olduvai domains and adjacent NOTCH2NL genes may function in a coordinated, complementary fashion to promote neurogenesis and human brain expansion in a dosage-related manner.
Much time and effort, as well as funding, is being devoted to Genome Wide Association Studies (GWAS) for identifying genetic causes of variation (single nucleotide polymorphisms or SNPs) in human cognitive abilities and educational attainments (CA and EA). After years of finding only very weak associations, usually failing to replicate, attention has turned to aggregates of otherwise non-significant SNPs (called polygenic scores, or PGS) and some associations with traits are now being reported. Here we show how, in the context of CA and EA as approximation measures, spurious correlations in GWAS/PGS can arise in a number of ways, particularly from genetic population structure. We review recent studies suggesting that attempts to control for such confounds have been quite inadequate, and also criticize the underlying statistical assumptions and genetic model.