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Transfer of Mosaic Embryos
Published in Darren K. Griffin, Gary L. Harton, Preimplantation Genetic Testing, 2020
Francesco Fiorentino, Ermanno Greco, Maria Giulia Minasi, Francesca Spinella
Accurate detection of mosaicism among embryos may also reduce the risk of early miscarriages and may increase implantation rates following transfer. To date, several issues, such as how mosaic embryos may “self-correct” and if preimplantation mosaicism may result in the birth of affected children, are still unresolved. More studies are welcome to provide better insights into the developmental genetics of mosaic embryos.
Discovery and research
Published in Peter S. Harper, The Evolution of Medical Genetics, 2019
The discovery of DNA instability in Huntington's disease and other trinucleotide repeat disorders has been only one of a number of research developments to show that the genome is less ‘hard-wired’ than had been previously thought likely. These cannot be given adequate space here but must at least have a mention, in particular the numerous aspects of gene function that are not directly dependent on the DNA sequence of an individual gene or the genome as a whole, and which are broadly covered by the term ‘epigenetics’, a term first used by Conrad Hal Waddington in the 1930s. Developmental genetics as a whole has been especially involved in these wider processes, which form part of genetics just as much as do the sequences of the individual genes that underlie them. Notable examples include the role of methylation in the activation and inactivation of gene function, which is responsible for a series of human developmental abnormalities.
Cancer as a genetic disorder
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Numerous oncogene loci are well recognised and are known to represent important growth factors or receptors involved in the regulation of cell division and other cell behaviours. These loci may also be important in early development and many (e.g. the RET oncogene) are involved in developmental malformations as well as tumours, linking the two important areas of cancer and developmental genetics.
Regulatory systems that mediate the effects of temperature on the lifespan of Caenorhabditis elegans
Published in Journal of Neurogenetics, 2020
Byounghun Kim, Jongsun Lee, Younghun Kim, Seung-Jae V. Lee
Aging is a gradual functional and structural decline in biological systems, leading to decreases in reproductive capacity and increased mortality. Aging is influenced by various genetic and environmental factors. Several model organisms, such as budding yeast, Caenorhabditis elegans, Drosophila melanogaster, and mice, have been used to determine how biological factors modulate aging and lifespan. The roundworm C. elegans, a small transparent nematode with a lifespan of only 2–3 weeks, is an invaluable model organism for aging research (Son, Altintas, Kim, Kwon, & Lee, 2019). By performing EMS mutagenesis and defining cell lineages for C. elegans (Brenner, 1974; Sulston, Schierenberg, White, & Thomson, 1983), Sydney Brenner and John Sulston established C. elegans as a model organism for developmental genetics. Their contributions provide the foundation for subsequent breakthrough discoveries in the biology of aging, using C. elegans as a primary model. Various genetic factors, including those acting in insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) signaling pathways, have been extensively studied using C. elegans (DiLoreto & Murphy, 2015; Kenyon, 2010a; Lee et al., 2015). Many reports also show how C. elegans lifespan is affected by environmental factors, including temperature, diet, and various external stresses.
Marla Sokolowski: and now for someone completely different
Published in Journal of Neurogenetics, 2021
H. Sofia Pereira, Karen D. Williams, J. Steven de Belle
During the mid-1970s, Marla Berger (now Sokolowski) – a curious undergraduate then in the Department Zoology at the University of Toronto – was tasked with a laboratory research project in Ellie Rapport’s (now E. Larsen, Professor Emeritus) Developmental Genetics course. For this project, she contemplated a comparison of two genetically manipulated strains of flies with obvious differences in morphology. The physical differences were easily explainable… an enzyme here, some pigment there, an extra tuft of bristles where only a few normally sprouted. Beyond these visible phenotypes, Marla found a more compelling challenge in understanding the biological and environmental factors that influenced how the flies behaved.
Women in science: a son’s perspective
Published in Journal of Neurogenetics, 2021
My mom’s research program really began when she was an undergraduate student in 1976 doing a project for a developmental genetics course. At the time, she was inspired by animal behavior and genetics as separate entities. In her undergraduate course, she designed a project to study the behavior of Drosophila melanogaster larvae. She discovered that some larvae tended to move a lot while foraging for food, while others moved relatively little. She called these larvae ‘rovers’ and ‘sitters’ respectively, before mapping the phenomena to the second pair of autosomal chromosomes. Her efforts earned her a B + because she was trying to study behavior and not development. As it turns out, this initial discovery leads to her first paper (Sokolowski, 1980) and her life’s work. A decade later, my mom and her first Ph.D. student, Steve de Belle, used a sixteen reciprocal cross procedure to reveal that the rover/sitter larval locomotory phenotype followed a Mendelian, autosomal dominant inheritance pattern (de Belle & Sokolowski, 1987). She then needed to get creative to profile foraging because full genome sequencing techniques to localize normal individual differences in behavior were not yet available. Two years later, she and her collaborators published a novel genetic method called lethal tagging to locate foraging (de Belle, Hilliker, & Sokolowski, 1989). Their subsequent long and challenging chromosome walk resulted in cloning the first gene for normal individual differences in behavior in any organism (Osborne et al., 1997). In this paper, they discovered that foraging encodes cGMP-dependent protein kinase (PKG) and that increasing foraging cDNA could convert the behavior of a sitter into a rover (Osborne et al., 1997). In the following twenty years, the Sokolowski lab studied the pleiotropic effects of the foraging gene and their foraging null generated through homologous recombination to display dosage effects on rover/sitter differences in other patterns of locomotion, food intake, and fat levels (Allen, Anreiter, Neville, & Sokolowski, 2017; Anreiter & Sokolowski, 2019). While characterizing foraging, my mom leveraged the pleiotropy and molecular tools she built and adapted to use foraging as a model to learn more about the fundamentals of behavior, evolution, development, and molecular biology. With foraging as her anchor, my mom, her team, and her collaborators identified clear and ecologically relevant biological phenomena. Some of these discoveries include the density-dependent and negative frequency-dependent selection effects on the foraging gene (Fitzpatrick, Feder, Rowe, & Sokolowski, 2007; Sokolowski, Pereira, & Hughes, 1997), and studies of the function of the foraging gene in eusocial insects (Ben-Shahar, Robichon, Sokolowski, & Robinson, 2002; Lucas & Sokolowski, 2009). When looking inward to the function of foraging, she has mapped phenotypes to tissue-specific, promoter-specific, and isoform-specific alterations in gene expression and epigenetics.