Concept: Thomas Hunt Morgan
Strabismus is a common condition with misalignment between two eyes that may lead to decrease of visual acuity, lack of binocularity, and diplopia. It is caused by heterogeneous environmental and genetic risk factors. Our previous research has identified new chromosomal susceptibility loci in 4q28.3 and 7q31.2 regions for comitant strabismus in Japanese families. We conducted a verification study by linkage analysis to narrow the chromosomal loci down to a single gene.
Idiopathic scoliosis (IS) is a spine deformity that affects approximately 3% of the population. The underlying causes of IS are not well understood, although there is clear evidence that there is a genetic component to the disease. Genetic mapping studies suggest high genetic heterogeneity, but no IS disease-causing gene has yet been identified. Here, genetic linkage analyses combined with exome sequencing identified a rare missense variant (p.A446T) in the centriolar protein gene POC5 that cosegregated with the disease in a large family with multiple members affected with IS. Subsequently, the p.A446T variant was found in an additional set of families with IS and in an additional 3 cases of IS. Moreover, POC5 variant p.A455P was present and linked to IS in one family and another rare POC5 variant (p.A429V) was identified in an additional 5 cases of IS. In a zebrafish model, expression of any of the 3 human IS-associated POC5 variant mRNAs resulted in spine deformity, without affecting other skeletal structures. Together, these findings indicate that mutations in the POC5 gene contribute to the occurrence of IS.
Garland E. Allen’s 1978 biography of the Nobel Prize winning biologist Thomas Hunt Morgan provides an excellent study of the man and his science. Allen presents Morgan as an opportunistic scientist who follows where his observations take him, leading him to his foundational work in Drosophila genetics. The book was rightfully hailed as an important achievement and it introduced generations of readers to Morgan. Yet, in hindsight, Allen’s book largely misses an equally important part of Morgan’s work - his study of development and regeneration. It is worth returning to this part of Morgan, exploring what Morgan contributed and also why he has been seen by contemporaries and historians such as Allen as having set aside some of the most important developmental problems. A closer look shows how Morgan’s view of cells and development that was different from that of his most noted contemporaries led to interpretation of his important contributions in favor of genetics. This essay is part of a special issue, revisiting Garland Allen’s views on the history of life sciences in the twentieth century.
The congenital cataract has been a clinically important cause of impaired vision development, making up about 10% of the cases of childhood blindness. Mutations of more than 40 genes have been identified causing congenital cataract with Mendelian inheritance, which indicated that it has an extremely high genetic heterogeneity. In this study, we recruited a large congenital cataract family and identified a missense mutation (c.143A>G: p.E48G) within gap junction protein alpha-3 (GJA3) gene in the proband using whole exome sequencing. Subsequent Sanger sequencing of this mutation in all family members revealed that this mutation cosegregated with the phenotype in the family with full penetrance. Our study identified a mutation in GJA3 that correlated with congenital cataract phenotype, which was not reported previously, and would be of benefit to the diagnosis of this genetic disorder. This finding expands the mutation spectrum of GJA3 and provides useful information for further study of the molecular pathogenesis of congenital cataract.
Absolute pitch and synesthesia are two uncommon cognitive traits that reflect increased neuronal connectivity and have been anecdotally reported to occur together in a same individual. Here we systematically evaluate the occurrence of syesthesia in a population of 768 subjects with documented absolute pitch. Out of these 768 subjects, 151(20.1%) reported synesthesia, most commonly with color. These self-reports of synesthesia were validated in a subset of 21 study subjects using an established methodology. We further carried out combined linkage analysis of 53 multiplex families with absolute pitch and 36 multiplex families with synesthesia. We observed a peak NPL LOD=4.68 on chromosome 6q, as well as evidence of linkage on chromosome 2 using a dominant model. These data establish the close phenotypic and genetic relationship between absolute pitch and synesthesia. The chromosome 6 linkage region contains 73 genes; several leading candidate genes involved in neurodevelopment were investigated by exon resequencing. However, further studies will be required to definitively establish the identity of the causative gene(s) in the region.
Fear/anxiety and anger/aggression greatly influence health, quality of life and social interactions. They are a huge burden to wellbeing, and personal and public economics. However, while much is known about the physiology and neuroanatomy of such emotions, little is known about their genetics - most importantly, why some individuals are more susceptible to pathology under stress.
Science standards have a long history in the United States and currently form the backbone of efforts to improve primary and secondary education in science, technology, engineering, and math (STEM). Although there has been much political controversy over the influence of standards on teacher autonomy and student performance, little light has been shed on how well standards cover science content. We assessed the coverage of genetics content in the Next Generation Science Standards (NGSS) using a consensus list of American Society of Human Genetics (ASHG) core concepts. We also compared the NGSS against state science standards. Our goals were to assess the potential of the new standards to support genetic literacy and to determine if they improve the coverage of genetics concepts relative to state standards. We found that expert reviewers cannot identify ASHG core concepts within the new standards with high reliability, suggesting that the scope of content addressed by the standards may be inconsistently interpreted. Given results that indicate that the disciplinary core ideas (DCIs) included in the NGSS documents produced by Achieve, Inc. clarify the content covered by the standards statements themselves, we recommend that the NGSS standards statements always be viewed alongside their supporting disciplinary core ideas. In addition, gaps exist in the coverage of essential genetics concepts, most worryingly concepts dealing with patterns of inheritance, both Mendelian and complex. Finally, state standards vary widely in their coverage of genetics concepts when compared with the NGSS. On average, however, the NGSS support genetic literacy better than extant state standards.
Ruffs (Aves: Philomachus pugnax) possess a genetic polymorphism for male mating behaviour resulting in three permanent alternative male reproductive morphs: (i) territorial ‘Independents’, (ii) non-territorial ‘Satellites’, and (iii) female-mimicking ‘Faeders’. Development into independent or satellite morphs has previously been shown to be due to a single-locus, two-allele autosomal Mendelian mode of inheritance at the S locus. Here, we use linkage analysis to map the chromosomal location of the F locus, which controls development into the Faeder morph, and draw further conclusions about candidate genes, assuming shared synteny with other birds.
Scientific outreach delivers science to the people. But it can also deliver people to the science. In this work, we report our experience from a large-scale public engagement project promoting genomic literacy among Danish high school students with the additional benefit of collecting data for studying the genetic makeup of the Danish population. Not only did we confirm that students have a great interest in their genetic past, but we were also gratified to see that, with the right motivation, adolescents can provide high-quality data for genetic studies.
Mutations generated by CRISPR/Cas9 in Arabidopsis are often somatic and are rarely heritable. Isolation of mutations in Cas9-free Arabidopsis plants can ensure stable transmission of the identified mutations to next generations, but the process is laborious and inefficient. Here we present a simple visual screen for Cas9-free T2 seeds, allowing us to quickly obtain Cas9-free Arabidopsis mutants at T2 generation. To demonstrate this in principle, we targeted two sites in the AUXIN BINDING PROTEIN 1 (ABP1) gene, whose function as a membrane-associated auxin receptor has been challenged recently. We obtained many T1 plants with detectable mutations near the target sites, but only a small fraction of T1 plants yielded Cas9-free abp1 mutations at T2 generation. Moreover, the mutations did not segregate in Mendelian fashion at T2 generation. However, mutations identified in the Cas9-free T2 plants were stably transmitted to T3 generation following Mendelian genetics. To further simplify the screening procedure, we simultaneously targeted two sites in ABP1 to generate large deletions, which can be easily identified by a PCR reaction. We successfully generated two abp1 alleles, which contained 1141 bp and 711 bp deletions in the ABP1 gene, respectively. All of the Cas9-free abp1 alleles we generated were stable and heritable. The method described here allows for effectively isolating Cas9-free heritable CRISPR mutants in Arabidopsis.