Biology subjects

Rohlfs, R. V.

Publications and source records attributed to Rohlfs, R. V..

5 recordsLinked to original sources

bioRxiv2024

Benchmarking for genotyping and imputation using degraded DNA for forensic applications across diverse populations

Advancements in sequencing and laboratory technologies have enabled forensic genetic analysis on increasingly low quality and degraded DNA samples. However, existing computational methods applied to genotyping and imputation for generating DNA profiles from degraded DNA have not been tested for forensic applications. Here we simulated sequencing data of varying qualities- coverage, fragment lengths, and deamination patterns-from forty individuals of diverse genetic ancestries. We used this dataset to test the performance of commonly used genotype and imputation methods (SAMtools, GATK, ATLAS, Beagle, and GLIMPSE) on five different SNP panels (MPS- plex, FORCE, two extended kinship panels, and the Human Origins array) that are used for forensic and population genetics applications. For genome mapping and variant calling with degraded DNA, we find use of parameters and methods (such as ATLAS) developed for ancient DNA analysis provides a marked improvement over conventional standards used for next generation sequencing analysis. We find that ATLAS outperforms GATK and SAMtools, achieving over 90% genotyping accuracy for the four largest SNP panels with coverages greater than 10X. For lower coverages, decreased concordance rates are correlated with increased rates of heterozygosity. Genotype refinement and imputation improve the accuracy at lower coverages by leveraging population reference data. For all five SNP panels, we find that using a population reference panel representative of worldwide populations (e.g., the 1000 Genomes Project) results in increased genotype accuracies across genetic ancestries, compared to ancestry-matched population reference panels. Importantly, we find that the low SNP density of commonly used forensics SNP panels can impact the reliability and performance of genotype refinement and imputation. This highlights a critical trade-off between enhancing privacy by using panels with fewer SNPs and maintaining the effectiveness of genomic tools. We provide benchmarks and recommendations for analyzing degraded DNA from diverse populations with widely used genomic methods in forensic casework. HighlightsO_LIBiallelic SNP panels: >92% genotyping accuracy for 10X data with ATLAS C_LIO_LIDegraded DNA impacts accuracy under sequencing depth of 10X coverage C_LIO_LIHigher accuracies across genetic ancestries achieved with a diverse reference panel C_LIO_LILeveraging population reference data is not applicable for small SNP panels C_LIO_LITrade-off between genotype accuracy and privacy when considering SNP panel size C_LI

genetics↗

bioRxiv2023

Microsatellites used in forensics are located in regions unusually rich in trait-associated variants

The 20 short tandem repeat (STR) markers of the combined DNA index system (CODIS) are the basis of the vast majority of forensic genetics in the United States. One argument for permissive rules about the collection of CODIS genotypes is that the CODIS markers are thought to contain information relevant to identification only (such as a human fingerprint would), with little information about ancestry or traits. However, in the past 20 years, a quickly growing field has identified hundreds of thousands of genotype-trait associations. Here we conduct a survey of the landscape of such associations surrounding the CODIS loci as compared with non-CODIS STRs. We find that the regions around the CODIS markers are enriched for both known pathogenic variants (>90th percentile) and for SNPs identified as trait-associated in genome-wide association studies (GWAS) ([≥]95th percentile in 10kb and 100kb flanking regions), compared with other random sets of autosomal tetranucleotide-repeat STRs. Although it is not obvious how much phenotypic information CODIS would need to convey to strain the "DNA fingerprint" analogy, the CODIS markers, considered as a set, are in regions unusually dense with variants with known phenotypic associations.

genetics↗

bioRxiv2020

Comparative regulomics reveals pervasive selection on gene dosage following whole genome duplication

Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80-100 million years ago. We find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Although ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards pseudogenization, strong evolutionary constraints have frequently also favoured symmetric shifts in gene dosage of both copies, likely to achieve gene dose reduction while avoiding accumulation of toxic mutations. Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one source of novel binding sites driving tissue-specific gains in expression. Our results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.

evolutionary biology↗

bioRxiv2018

Illuminating women’s hidden contribution to the foundation of theoretical population genetics

Plentiful evidence shows an historic and continuing gender gap in participation and success in scientific research. However, less attention has been directed at clarifying obscured contributions of women to science. The lack of visible women role models (particularly in computational fields) contributes to a reduced sense of belonging and retention among women. We seek to counteract this cycle by illuminating the contribution of women programmers to the foundation of our own fields--population and evolutionary genetics. We consider past acknowledged programmers (APs), who developed, ran, and sometimes analyzed the results of early computer programs. Due to authorship norms at the time, these programmers were credited in the acknowledgments sections of manuscripts, rather than being recognized as authors. For example, one acknowledgement reads \"I thanks Mrs. M. Wu for help with the numerical work, and in particular for computing table I.\". We identified APs in Theoretical Population Biology articles published between 1970 and 1990. While only 7% of authors were women, 43% of APs were women. This significant difference (p = 4.0x10-10) demonstrates a substantial proportion of womens contribution to foundational computational population genetics has been unrecognized. The proportion of women APs, as well as number of APs decreased over time. These observations correspond to the masculinization of computer programming, and the shifting of programming responsibilities to individuals credited as authors (likely graduate students). Finally, we note recurrent APs who contributed to several highly-cited manuscripts. We conclude that, while previously overlooked, historically, women have made substantial contributions to computational biology.

scientific communication and education↗

bioRxiv2017

Subfunctionalization versus neofunctionalization after whole-genome duplication

The question of what is the predominant evolutionary fate of genes after duplication events has been hotly debated for decades1,2. Two recently published articles in Nature (Lien et al.3) and Nature Genetics (Braasch et al.4) investigated the regulatory fate of gene duplicates after the salmonid-specific (Ss4R) and teleost specific (Ts3R) whole genome duplication (WGD) events, respectively. Both studies relied on tissue expression atlases for estimating regulatory divergence and used closely related unduplicated sister taxa (i.e. Northern pike and the spotted gar, respectively) as proxies for the ancestral expression state. Surprisingly, the two studies reach very different conclusions about the evolutionary mechanisms impacting gene expression after WGD. Braasch et al.4 concluded that the expression divergence was consistent with partitioning of tissue regulation between duplicates (subfunctionalization), while Lien et al.3 concluded that most divergence in tissue regulation were consistent with one copy maintaining ancestral tissue regulation while the other having diverged (in line with neofunctionalization). Here we show that this striking discrepancy in the conclusions of the two studies is a consequence of the data analysis approaches used, and is not related to underlying differences in the data.

evolutionary biology↗