Acknowledgement to Reviewers of OBM Genetics in 2021

The editors of OBM Genetics would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2021. We greatly appreciate the contribution of expert reviewers, which is crucial to the journal's editorial process. We aim to recognize reviewer contributions through several mechanisms, of which the annual publication of reviewer names is one. Reviewers receive a voucher entitling them to a discount on their next LIDSEN publication and can download a certificate of recognition directly from our submission system. Additionally, reviewers can sign up to the service Publons (https://publons.com) to receive recognition. Of course, in these initiatives we are careful not to compromise reviewer confidentiality. Many reviewers see their work as a voluntary and often unseen part of their role as researchers. We are grateful to the time reviewers donate to our journals and the contribution they make.

Anatomical Variation, Hominins, Species, and Self-Domestication

The evolution of hominins, members of the zoological tribe Hominini, has been a much-studied topic, and the construction of phylogenetic trees has been the key method in molecular evolutionary studies. How scientists determine the phylogenetic trees are governed by the assumptions they place on the construction of similarities and differences in morphological traits, the differences in the number of base pairs in the genomes, and the number of similar gene clusters that code for traits (haplotypes) or are error sequences (SNPs). Among the several methods employed for the construction of a phylogenetic tree, mathematical methods (utilized for sorting data, including fabrication of algorithms) are the most significant ones; also, the nature of population structuring plays an important role in the evolutionary process. In this paper, I will not only describe the drawbacks of current assumptions in hominin evolution during the Middle Pleistocene era (based on fossil evidence) but also the aspects of brain evolution and the self-domestication of our species. The evolution of the brain is usually associated with an increase in neurons and other types of cells associated with signal processing (connectivity) and memory. Assessing actual neuron counts in fossils is challenging; moreover, new research has shown decreased neuron numbers in the neocortex and demonstrated large counts in the cerebellum, leading to a decreased focus on brain size. The idea of increased brain size in the Pleistocene era without a substantial increase in the evidence of cognitive activity in complex behavior residues might be explained by increased myelination to provide additional insulation in Ice Age conditions and faster transition of signals due to increased competition for reduced food supplies. Other cold-adaptation features can also be noted. Such a model can provide a new approach to assess the apparent brain size reduction in the Upper Paleolithic period.

Would I have Wanted to Know? A Qualitative Exploration of Women’s Attitudes, Beliefs and Concerns about Non-Invasive Prenatal Testing for de novo Genetic Conditions after having a Child with a de novo Genetic Disorder

Non-invasive prenatal testing (NIPT) for a panel of 25 single gene disorders became available in Western Australia in 2020 and potentially may be able to test for panels of hundreds of disorders as is the case with reproductive carrier screening. How this information would be used by parents in a population screening model is unknown. We used a phenomenological approach to explore retrospectively whether mothers of children with single gene or chromosomal disorders would have wanted to know about their child’s genetic diagnosis prior to delivery. Themes were identified such as having a child with a de novo disorder and effect on pregnancy outcomes in hypothetical situations, impact on family function, the diagnostic journey and personal growth. These themes related to both the concept of expanded NIPT (ENIPT) and the situation of having a child with a de novo genetic disorder that could now hypothetically be detected through ENIPT. Opinions were divided about whether participants would have wanted to know about their affected child’s condition, indicating any expanded NIPT testing panels would need to be offered in the context of an appropriate comprehensive counselling program. How this would be provided on a population screening level and the role of genetic counselling needs further exploration.

Addressing Uncertainty: The Emergence of the CRMS/CFSPID Diagnostic Category Following Newborn Screening for Cystic Fibrosis

This article uses cystic fibrosis as a case study to examine how physicians and scientists have navigated uncertainty following newborn screening. Despite the many benefits of newborn screening, including earlier diagnosis, therapeutic intervention, and a reduced diagnostic odyssey, this public health approach also comes with challenges. For example, physicians began to document infants with indeterminate diagnoses - those with a positive screen who did not clearly fit into the cystic fibrosis or “normal” categories - by the early twenty first century. As a means of addressing this uncertainty and to facilitate long-term follow up of such infants, the U.S. Cystic Fibrosis Foundation recommended in 2009 that a new diagnostic term, CFTR-related metabolic syndrome (CRMS), be used. However, the CRMS label was not favored in Europe and a different term, cystic fibrosis screen positive, inconclusive diagnosis (CFSPID), was adopted in 2015 instead. Efforts to address the uncertainty associated with indeterminate diagnoses have been complicated, as stakeholders have held differing views about whether the screening algorithms should aim to maximize or minimize CRMS/CFSPID cases. Many who favor the identification of babies with CRMS/CFSPID note that they are at increased risk of developing symptoms and signs consistent with a cystic fibrosis diagnosis. In contrast, those who support algorithms that reduce CRMS/CFSPID cases point to iatrogenic harms associated with the medicalization of children who may remain healthy into adulthood. Furthermore, investigators have grappled with how best to ensure equity in newborn screening among different racialized groups while concomitantly attempting to minimize false positive results. These issues are applicable beyond the context of cystic fibrosis, especially as programs contemplate the incorporation or expanded use of next generation sequencing in algorithms for a wide range of diseases, and this history highlights how efforts to reduce uncertainty in one setting can lead to new and persistent sources of uncertainty in other areas.

Screening Before We Know: Radical Uncertainties in Expanded Prenatal Genetics

In this article, we discuss the radical uncertainties unleashed by expanded prenatal genetics. We show how we are now routinely screening fetuses in the absence of two essential sorts of information. At the population level, we do not have sound, unbiased data about the prevalence, penetrance, and clinical variability of most mutations. At the level of the proband, it is often too soon to discern relevant information about the fetus’ phenotype. First, we outline the longstanding ethical objections to newborn screening for poorly understood genetic anomalies and disorders, and explain how it limits our understanding of their penetrance and variability. Next, we contrast the strong restrictions and regulations around newborn screening with the more laissez-faire framework for prenatal screening, using the rollout of non-invasive prenatal testing (NIPT) as the timeliest and most illuminating example. We show how new conditions are added to NIPT kits based on technological feasibility and profit motive, leading to widespread prenatal screening for incompletely understood genetic disorders. Finally, we explore the myriad dilemmas that ‘screening before we know’ creates for counsellors, caregivers, and prospective parents in the age of non-invasive prenatal genetic screening, and argue for an approach that openly embraces the radical uncertainties we face.

Genetic Screening of Cervical Cancer

Medical genetics plays an important role in the screening and prevention of numerous diseases. Thus, it is important to develop effective screening and prevention programs and improve the assessment of the susceptibility of diseases. The development of screening and prevention programs depends on the identification of early biomarkers (including functional and behavioral) for the risk and onset of the disease, and such programs need to be designed according to internationally accepted criteria. Cervical cancer represents a very relevant disease from the health and social perspective; around 528,000 new cases are diagnosed every year globally, of which, 85% are from developing countries, representing almost 12% of all cancers in females. Substantial reductions in the incidence of and mortality from cervical cancer have been observed after the introduction of prevention campaigns with the implementation of cervical screening programs through Papanicolaou (Pap) tests and, in particular, following the introduction of organized programs which guarantee a high level of screening coverage, as well as, the quality and continuity of diagnostic-therapeutic procedures. It is estimated that Pap smear screening every 3-5 years provides 80% protection against the onset of cancer. Advances in diagnostic techniques, particularly the development of easy-to-use molecular genetic tests, are replacing the use of the established Pap smear as a screening tool. This is possible owing to the discovery in 1975 that some cellular morphological changes (koilocytosis) were related to the presence of a Human Papillomavirus (HPV) infection. The HPV test is performed on a small sample of cells taken from the cervix, similar to the Pap test; however, it is not a morphological exam but a molecular biology exam that detects the presence of HPV by identifying its deoxyribonucleic acid (DNA) or messenger ribonucleic acid (mRNA). The results of numerous experimental studies have demonstrated a greater sensitivity of this test compared to the sensitivity of the traditional Pap test. However, the HPV test has a lower specificity due to two main factors: 1) The HPV test is based on the search for the types of viruses that have a greater oncogenic potential, and 2) It does not discriminate between transient infections and persistent and productive infections. The most widely used molecular tests are based on the search for HPV sequences and genotyping using molecular biology techniques, such as direct hybridization, qualitative polymerase chain reaction (PCR), and viral nucleotide sequencing.

Prenatal Testing – What Is It Good For? A Review and Critique

The goals of prenatal testing remain controversial and reflect competing interests of public health, patient rights, disability activists, scholars, feminist critics, commercial laboratories, judiciary/legislative trends, and medical science. This paper reviews and critiques the most common justifications of prenatal testing for fetal aneuploidy that have been put forth over the half century of its existence: reducing the medical and economic burden to society of genetic disease through selective abortion, allowing parents to avoid raising a child with disabilities, preventing the suffering associated with chromosomal and genetic disorders, emotional reassurance about the health of the baby, and medical and emotional preparation for the birth of a baby with a disability. Each of these goals has problematic aspects, as do some of the criticisms of these goals. The most striking shortcoming of the justifications for prenatal testing is a dearth of research about potential medical, psychological, or adaptational benefits of prenatal testing, especially for aneuploidy, for babies and families, beyond the option of pregnancy termination.

Understanding the Regulation of Transcription in Mental Illness

Advances in clinical psychiatry have been less than hoped for relative to the achievements in neuroscience. However, developments in neuromodulation and psychedelic therapy are promising. The efficacy of such treatments and canonical pharmacotherapies benefit from genetics and personalized medicine. Moreover, recent studies on the perturbation of transcription, including chromatin remodeling, in mental illness emphasized the importance of single-cell qPCR as an investigatory method that bolstered psychiatry. This technique demonstrated chromatin remodeling as a biomarker for addiction and the underlying mechanism of depression. If personalized medicine, along with canonical and newer therapies, can mediate and regulate transcription, epidemics in depression and addiction can be mitigated. This motivates investigators to continue to use single-cell transcription measures in models of mental illness for translational medicine.

Quadruple Screening in the Age of Cell-Free DNA: What are We Losing?

Cell-free DNA has emerged as the most reliable, non-invasive prenatal screening tool for fetal aneuploidies. It has come to replace the previously widely used quadruple screen offered in the second trimester of pregnancy. This change comes with improved detection for aneuploidy but also presents potential gaps in prenatal diagnosis including detection of open fetal defects and emerging data on prediction of adverse pregnancy outcomes. This review article provides a historical summary of the quadruple marker screen and evaluates the intersection of this screen with cell-free DNA. Furthermore, it discusses points to consider as providers trend toward cell-free DNA testing alone and reviews potential options to remedy any disparities.

Plant Breeding Integrated with Genomic-Enabled Prediction

Plant breeding programs have used conventional breeding methods, such as hybridization, induced mutations, and other methods to manipulate the plant genome within the species' natural genetic boundaries to improve crop varieties. However, repeatedly using conventional breeding methods might lead to the erosion of the gene reservoir, thereby rendering crops vulnerable to environmental stresses and hampering future progress in crop production, food and nutritional security, and socio-economic benefits. Integrating innovative technologies in breeding programs to accelerate gene flow is critical for sustaining global plant production. Genomic prediction is a promising tool to assist the rapid selection of premiere genotypes and accelerate breeding gains for climate-resilient plant varieties. This review surveys the annals and principles of genomic-enabled prediction. Based on the problem that is investigated through the prediction, as well as several other factors, such as trait heritability, the relationship between the individuals to be predicted and those used to train the models for prediction, the number of markers, sample size, and the interaction between genotype and environment, different levels of accuracy have been reported. Genomic prediction might play a decisive role and facilitate gene flow from gene bank accessions to elite lines in future breeding programs.