Biology subjects

Backenroth, D.

Publications and source records attributed to Backenroth, D..

3 recordsLinked to original sources

bioRxiv2022

Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14th century

We report genome-wide data for 33 Ashkenazi Jews (AJ), dated to the 14th century, following a salvage excavation at the medieval Jewish cemetery of Erfurt, Germany. The Erfurt individuals are genetically similar to modern AJ and have substantial Southern European ancestry, but they show more variability in Eastern European-related ancestry than modern AJ. A third of the Erfurt individuals carried the same nearly-AJ-specific mitochondrial haplogroup and eight carried pathogenic variants known to affect AJ today. These observations, together with high levels of runs of homozygosity, suggest that the Erfurt community had already experienced the major reduction in size that affected modern AJ. However, the Erfurt bottleneck was more severe, implying substructure in medieval AJ. Together, our results suggest that the AJ founder event and the acquisition of the main sources of ancestry pre-dated the 14th century and highlight late medieval genetic heterogeneity no longer present in modern AJ.

genetics↗

bioRxiv2020

Utility of polygenic embryo screening for disease depends on the selection strategy

Polygenic risk scores (PRSs) have been offered since 2019 to screen in vitro fertilization embryos for genetic liability to adult diseases, despite a lack of comprehensive modeling of expected outcomes. Here we predict, based on the liability threshold model, the expected reduction in complex disease risk following polygenic embryo screening for a single disease. Our main finding is that a strong determinant of the potential utility of such screening is the selection strategy, a factor that has not been previously studied. Specifically, when only embryos with a very high PRS are excluded, the achieved risk reduction is minimal. In contrast, selecting the embryo with the lowest PRS can lead to substantial relative risk reductions, given a sufficient number of viable embryos. For example, a relative risk reduction of {approx}50% for schizophrenia can be achieved by selecting the embryo with the lowest PRS out of five viable embryos. We systematically examine the impact of several factors on the utility of screening, including the variance explained by the PRS, the number of embryos, the disease prevalence, the parental PRSs, and the parental disease status. When quantifying the utility, we consider both relative and absolute risk reductions, as well as population-averaged and per-couple risk reductions. We also examine the risk of pleiotropic effects. Finally, we confirm our theoretical predictions by simulating "virtual" couples and offspring based on real genomes from schizophrenia and Crohns disease case-control studies. We discuss the assumptions and limitations of our model, as well as the potential emerging ethical concerns.

genetics↗

bioRxiv2019

A test for Hardy-Weinberg equilibrium on the X chromosome for sex-biased admixed populations

Genome-wide scans for deviations from Hardy-Weinberg equilibrium (HWE) are commonly applied to detect genotyping errors. In contrast to the autosomes, genotype frequencies on the X chromosome do not reach HWE within a single generation. Instead, if allele frequencies in males and females initially differ, they oscillate for a few generations towards equilibrium. Several populations world-wide have experienced recent sex-biased admixture, namely, their male and female founders differed in ancestry and thus in allele frequencies. Sex-biased admixture makes testing for HWE difficult on X, because deviations are naturally expected, even under random mating post-admixture and error-free genotyping. In this paper, we develop a likelihood ratio test and a{chi} 2 test that detect deviations from HWE on X while allowing for natural deviations due to sex-biased admixture. We demonstrate by simulations that our tests are powerful for detecting deviations due to non-random mating, while at the same time they do not reject the null under historical sex-biased admixture and random mating thereafter. We also demonstrate that when applied to 1000 Genomes project populations (e.g., as a quality control step), our tests reject fewer SNPs (among those showing frequency differences between the sexes) than other tests.

genetics↗