Introduction to Genetics

The textbook outlines the cytological foundations of heredity, the regularities of Mendelian genetics, the chromosomal theory of heredity, the basics of molecular genetics and genetic engineering, the patterns of inheritance during distant hybridization, polyplodia and mutagenesis. Special attention is paid to the heterosis and genetics of populations. A significant part of the data is presented in the form of figures, diagrams, graphs and tables that facilitate the understanding of the material presented. Meets the requirements of the federal state educational standards of higher education of the latest generation. For students of higher educational institutions studying in agronomic specialties.

Broad spectrum of CRISPR-induced edits in an embryonic lethal gene

Mendelian genetics poses practical limitations on the number of mutant genes that can be investigated simultaneously for their roles in embryonic development in the mouse. While CRISPR-based gene editing of multiple genes at once offers an attractive alternative strategy, subsequent breeding or establishment of permanent mouse lines will rapidly segregate the different mutant loci again. Direct phenotypic analysis of genomic edits in an embryonic lethal gene in F0 generation mice, or F0 mouse embryos, circumvents the need for breeding or establishment of mutant mouse lines. In the course of genotyping a large cohort of F0 CRISPants, where the embryonic lethal gene T/brachyury was targeted, we noted the presence of multiple CRISPR-induced modifications in individual embryos. Using long-read single-molecule Nanopore sequencing, we identified a wide variety of deletions, ranging up to 3 kb, that would not have been detected or scored as wildtype with commonly used genotyping methods that rely on subcloning and short-read or Sanger sequencing. Long-read sequencing results were crucial for accurate genotype–phenotype correlation in our F0 CRISPants. We thus demonstrate feasibility of screening manipulated F0 embryos for mid-gestation phenotypic consequences of CRISPR-induced mutations without requiring derivation of permanent mouse lines.

Genomic medicine in the Middle East

We discuss the current state of genomic medicine in Arab countries of the Middle East, a region with outsized contribution to Mendelian genetics due to inbreeding yet has poor representation in global variome datasets. We focus on genomic testing, clinical genetics, and genetic counseling services along with associated training and research programs. Finally, we highlight opportunities for improvement in genomic medicine services in this region.

Group size planning of breedings of gene-modified animals

Animal breeding is time-consuming, costly, and affected by stochastic events related to Mendelian genetics, fertility, and litter size. Careful planning is mandatory to ensure a successful outcome using the least number of animals, hence adhering to the 3Rs of animal welfare. We have developed an R package, accessible also through an interactive website, that optimizes breeding design and provides a comprehensive report suitable for any breeder of genetically defined traits.

The Second Allele: A Key to Understanding the Timing of Sporadic and Hereditary Colorectal Tumorigenesis

Our understanding of the molecular basis of colorectal neoplasia is derived from Mendelian genetics, with tumor suppressor genes contributing more to the deregulation of growth than oncogenes. In patients with hereditary syndromes, expression of one allele of a key tumor suppressor gene is absent at birth. The loss of the expression of the second allele precipitates tumorigenesis. However, there are multiple ways in which the expression of the second allele of a tumor suppressor gene is lost. Here, we review these ways and their possible effect on phenotype.

Group size planning of breedings of gene-modified animals

Animal breeding is time-consuming, costly, and affected by stochastic events related to Mendelian genetics, fertility, and litter size. Careful planning is mandatory to ensure a successful outcome using the least number of animals, hence adhering to the 3Rs of animal welfare. We have developed an R package, accessible also through an interactive website, that optimizes breeding design and provides a comprehensive report suitable for any breeder of genetically defined traits.

What colour are your eyes? Teaching the genetics of eye colour & colour vision. Edridge Green Lecture RCOphth Annual Congress Glasgow May 2019

Eye colour and colour perception are excellent examples to use when teaching genetics as they encompass not simply the basic Mendelian genetics of dominant, recessive and X-linked disorders, but also many of the new concepts such as non-allelic diseases, polygenic disease, phenocopies, genome-wide association study (GWAS), founder effects, gene-environment interaction, evolutionary drivers for variations, copy number variation, insertions deletions, methylation and gene inactivation. Beyond genetics, colour perception touches on concepts involving optics, physics, physiology and psychology and can capture the imagination of the population, as we saw with social media trend of “#the dress”. Television shows such as Game of Thrones focused attention on the eye colour of characters, as well as their Dire-wolves and Dragons. These themes in popular culture can be leveraged as tools to teach and engage everyone in genetics, which is now a key component in all eye diseases. As the explosion of data from genomics, big data and artificial intelligence transforms medicine, ophthalmologists need to be genetically literate. Genetics is relevant, not just for Inherited Retinal Diseases and congenital abnormalities but also for the leading causes of blindness: age-related macular degeneration, glaucoma, myopia, diabetic retinopathy and cataract. Genetics should be part of the armamentarium of every practicing ophthalmologist. We need to ask every patient about their family history. In the near future, patients will attend eye clinics with genetic results showing they are at high risk of certain eye diseases and ophthalmologists will need to know how to screen, follow and treat these patients.

From the Modern Synthesis to the Molecular Synthesis: updating how we teach and assess evolution by natural selection

Evolution by natural selection is recognized as both the most important concept in undergraduate biology and the most difficult to teach. Unfortunately, teaching and assessment of evolution have been impaired by legacy approaches that focus on Darwin's original insights and the Modern Synthesis' integration of Mendelian genetics, but ignore or downplay advances from what we term the Molecular Synthesis. To create better alignment between instructional approaches and contemporary research in the biosciences, we propose that the primary learning goal in teaching evolution should be for students to connect genotypes, phenotypes, and fitness. To support this approach, we developed and tested assessment questions and scoring rubrics called the Extended Assessing Conceptual Reasoning of Natural Selection (E-ACORNS) instrument. Initial E-ACORNS data suggest that after traditional instruction, few students recognize the molecular synthesis, prompting us to propose that introductory course sequences be re-organized with the molecular synthesis as their central theme.