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PNAS Papers Describe Amish De Novo Mutation Decrease, RNA Sequencing Method, Precision Med Results

Researchers from the University of Maryland School of Medicine and elsewhere describe de novo mutation patterns in almost 1,500 parent-child trios profiled for the Trans-Omics for Precision Medicine (TOPMed) program. After uncovering 93,325 single nucleotide de novo mutations with whole-genome sequence data for 1,465 trios from diverse populations with European, African, or Latino ancestry, the team focused in on Amish individuals — a founder population with lower-than-usual de novo mutation rates compared with other European or non-European populations, perhaps due to environmental contributors. "[T]he mutational differences we found in the Amish stand in contrast to the relative homogeneity seen across the other diverse human populations we analyzed," the authors write, "and suggest that additional work is needed to better appreciate the forces shaping human mutational processes at fine scales."

Investigators at Peking University and other centers in China and the US share an RNA sequencing strategy that circumvents the typical "second strand" complementary double-stranded DNA synthesis step, done using reverse transcription. The alternative RNA-seq method — known as "Sequencing Hetero RNA-DNA hybrid," or SHERRY — relies on PCR amplification of fragments produced when a bacterial transposase enzyme called Tn5 is used to cut and incorporate adaptor sequences to RNA-DNA "heteroduplexes." Based on their results, the authors argue that SHERRY "greatly improves the robustness of low-input RNA-seq with a simplified experimental procedure," showing "superior cross-sample robustness and comparable detectability for both bulk RNA and single cells compared with other commonly used methods."

A Human Longevity-led team shares results from a years-long precision medicine program that collected elective genome sequencing, deep phenotyping and imaging insights, metabolomic profiles, clinical lab test results, and other data from 1,190 adult participants. By integrating these diverse data types for the prospective study, the investigators found that around one in six participants carried one or more pathogenic or likely pathogenic variants. Moreover, 1 in 9 adult individuals had genetic features that corresponded to their traits or conditions, ranging from heart conditions to endocrine disease, they note, while 61 heterozygous individuals with one affected version of a disease-associated gene showed related metabolic shifts. GenomeWeb has more on the study, here.