Must-see new studies in genetics

Genetics just might be the single-fastest advancing field in the life sciences.

The information stored in genomes provides instructions for producing every living organism on our planet. Technologies such as CRISPR, which can be used to selectively modify the DNA of organisms, and methods such as direct-to-consumer genetic testing, where customers or patients receive genetic tests without involving a health-care-provider, have revolutionized health and science for researchers and the public alike.

Twenty years after the completion of the Human Genome Project, whole-genome sequencing is more common, fast, and affordable than ever before. Now we have massive volumes of sequencing data that can be used for biomedical research and clinical advances. Genetic science has an enormous health and economic impact on our world today.

Recently, we covered groundbreaking studies in the field of biomedicine. In this installment of our Trends in Research series, here are five new, exciting peer-reviewed papers that contribute fresh discoveries in genetics and genomics.

Source: Gao, Gerstein. The LatentDAG network. 

A new network model for gene relationships

Representing core gene expression activity relationships using the latent structure implicit in Bayesian networks  

Bioinformatics (40-8). Yale University: Jiahao Gao, Mark Gerstein.

Research question and importance

• Gene regulatory networks (GRN) play a central role in morphogenesis, the creation of body structure.
• In order to determine a GRN, scientists can use chromatin immunoprecipitation followed by sequencing (ChIP-seq), which establishes a connection between transcription factors (TFs) and their target genes.
• But such networks have been highly difficult to interpret due to false and missing network connections. Authors hypothesize that a Bayesian network structure could accurately represent the underlying relationships between genes in a GRN.

Methodology

• Authors applied the Bayesian network structure learning methods to a gene expression dataset.

Results

• The resulting network (LatentDAG) was about 400 times sparser than a co-expression network built from the same data.
• LatentDAG illuminated unique properties of genes and highlighted genes that contributed the strongest signal to gene co-expression.
• LatentDAG works better than other biological networks in tasks such as predicting gene conservation and clustering genes.

Implications

• An accurate network representing the GRN could help scientists pinpoint genetic mutations behind diseases, leading to more effective diagnosis and treatment.
• Pharmaceutical companies could use LatentDAG to speed up the drug development process by quickly identifying key genes.

The genetics of centenarians

The Druze Star.

The d3GHR carrier epigenome in Druze clan longevity  

Scientific Reports (14). University of Haifa, Tel Aviv Sourasky Medical Center, Rambam Health Care Campus: Ghadeer Falah, Alina Kurolap, Tamar Paperna, Nina Ekhilevitch, Nivin Moustafa, Nadine Damouny-Naoum, Yam Amir, LItal Sharvit, Rihan Moghrabi, Gamal Hassoun, Fuad Fares, Hagit Baris Feldman & Gil Atzmon

Research question and importance

• The Druze, a distinct ethnic group in Israel dating back to the eleventh century, have a high ratio of long-lived men carrying the “d3 growth hormone receptor” (d3GHR) isoform, which allows men to live 10 years longer on average.
• DNA methylation is a crucial epigenetic modification with a significant role in human aging. This study investigates whether the different isoforms of the GHR gene in the Druze show different DNA methylation patterns.
• Hypothesis: Individuals with homozygous deletion will have a beneficial DNA methylation pattern, allowing them to exhibit younger biological age.

Methodology

• Researchers analyzed the genotypes of 73 individuals from six unrelated families in four Druze villages, including multiple centenarians. They then conducted further analyses on the d3GHR polymorphism, DNA methylation data, differentially methylated probes, differentially methylated regions, and epigenetic clocks.

Results

• Researchers found a significant negative correlation between DNA methylation levels and age.
• The d3GHR group was over 4 years biologically younger than the other groups surveyed and male centenarians were far more likely to carry this polymorphism.

Implications

• These results contribute to the global understanding of beneficial gene variations for healthy aging, enabling clinicians to develop personalized anti-aging therapies.

Retracing the extinction of a lost species

The yellow warbler. Source: Wikipedia.

Museum genomics provide insight into the extinction of a specialist North American warbler species

Scientific Reports (14). Smithsonian’s National Zoo and Conservation Biology Institute: Paige A. Byerly, Anna M. Kearns, Andreanna Welch, Margad-Erdene Ochirbat, Peter P. Marra, Amy Wilson, Michael G. Campana & Robert Fleischer

Research question and importance

• One of the nine avian species to go extinct in North America since the 1800s was the Bachman’s warbler (Vermivora bachmanii), but specific factors behind its extinction are not well documented.
• Researchers conducted a genomic analysis using museum collections in order to investigate the hypothesis that long-term population isolation contributed to the species’ extinction.

Methodology

• Researchers used mtDNA and nuclear SNPs from museum specimens collected between 1988 and 1924, investigating population connectivity and estimating effective population size,
• Toe pad tissue samples from 55 specimens from seven institutions underwent organic DNA extraction, mitochondrial PCR analysis, and sequence analysis.

Results

• Researchers found no signals of strong population structuring. Data collected in the study suggests that the species did not experience long periods of isolation.
• Results suggest that Bachman’s warblers were naturally uncommon due to the rarity of their breeding habitat. Researchers concluded that habitat destruction rather than population isolation exacerbated the species path towards extinction.

Implications

• Researchers and policymakers can apply this study to develop better conservation strategies for endangered American bird species.
• The study also provides a use-case and methodology for collecting genome information from museum collections.

Artificial bacterial replication genes

Reconstruction of a robust bacterial replication module  

Nucleic Acids Research (52-18). Chinese Academy of Sciences and Shanghai Jiao Tong University: Tao Wang, Fan He, Ting He, Chen Lin, Xin Guan, Zhongjun Qin, Xiaoli Xue.

Research question and importance

• In synthetic biology, numerous studies have had success with functional modularization, which arranges metabolic genes into modular units in order to enhance metabolic efficiency.
• But few studies have explored functional modularization in genetic processes, such as replication and transcription.
• Researchers attempted to reconstruct a bacterial replication model for coli by artificially clustering the dispersed genes used in chromosomal replication.

Methodology

• Authors built a bacterial replication module plasmid (pRC) by clustering 23 genes involved in DNA replication and sequentially deleting these genes from their scattered chromosome locations. They grew modified coli strains and quantified the newly synthesized DNA.
• Authors performed flow cytometry, replication runout and initiation, microscopy, Western blot, RNA-sequencing, genetic stability analysis, and pulsed-field gel electrophoresis (PFGE) analyses, among others.

Results

• Integrating pRC into the chromosome successfully led to better DNA synthesis efficiency, showing robust DNA replication.
• Authors demonstrated the possibility of artificial DNA replication.

Implications

• Fully customizable genomes could be possible in the near future. That would enable scientists to create bacteria—or even other life forms—capable of tasks like producing biofuels and degrading plastics.

A comprehensive review of clay’s potential to block antibacterial resistance

Mitigation potential of antibiotic resistance genes in water and soil by clay-based adsorbents  

NPJ Materials Sustainability (26). Raj Mukhopadhyay (Carnegie Mellon University), Barbara Drigo & Binoy Sarkar (University of South Australia).

Research question and importance

• In a world where antibiotics are used extensively worldwide, and antibiotic resistance has been identified as one of the most significant challenges to human health, antibiotic residues discharged into the environment are known to influence antibiotic resistance genes (ARGs).
• Removing ARGs from contaminated water and soil is extremely challenging. Methods such as oxidation, membrane separation, and chlorination are energy-intensive, expensive, and not eco-friendly.
• Clay mineral-based adsorbents have great potential as a way to filter ARGs, but there are questions about their efficiency. Authors of the study provide insight into the opportunities and challenges of using clay-based materials.

Methodology

• Authors discuss ecological and human health risks of ARGs, the primary sources of antibiotic residues in wastewater, and the prevalence of antimicrobial resistance.
• The study then describes factors affecting ARG transfer and transformation, such as the presence of minerals and organic matter.
• Lastly, authors analyze the removal of ARGs by clay-based adsorbents.

Results

• Authors identify the primary research gaps for future studies on clay-based adsorbents. These include: A source identification of antibiotic residues; Studies that explore the adsorption capacity of various types of clay minerals; Generation of databases on ARGs for routine monitoring.

Implications

• Heightened use of clay-based adsorbents could offer a sustainable solution—both eco-friendly and affordable—for filtering ARGs, benefitting farmers, wastewater treatment plants, and global health.