Thota Kanishka Rao, Amity University Kolkata
Meier-Gorlin syndrome, or MGS, is a genetic disorder that causes dwarfism, small ears, a small brain, missing patella and other skeletal abnormalities. In severe cases, MGS results in miscarriages and stillbirths.
Researchers tried to study this recessive, autosomal disorder in a unique way, i.e, by placing mutant human genes into fruit flies. Specifically, they looked at one of the genes involved in MGS called Orc6. In 2017, it was reported that researchers used this animal model to probe the function of one human Orc6 mutation—a Lysine 23 to Glutamic acid (K23E) substitution. In people with MGS, the K23E causes a similar disorder as the Orc6 mutation.
These two changes are intriguing to contrast, in light of the fact that position 23 is close to the front, or the N-terminal domain, of the long chain of associated amino acids that folds to frame the Orc6 protein. Position 225 is close to the end, or the C-terminal domain, of the Orc6 protein strand.
Orc6 is part of the Origin Recognition Complex, or ORC. This complex of proteins is fundamental to start DNA replication in a cell, regardless of whether yeast, natural product fly, human or some other eukaryotic organism. Without DNA division, a cell cannot divide and an organism cannot grow. Poor division will result in stunted growth as seen in MGS.
The two mutations have distinctive fundamental molecular mechanisms, the two of them cause deficient pre-replicative complex arrangement and decreased DNA replication, and they produce a similar phenotype in MGS patients.
An important part of the research was creating chimeric Orc6 genes that are part human gene and part fruit fly gene. It is necessary as putting human Orc6 genes into fruit flies is not able to replace the function of the fruit fly Orc6, due to the difference in Orc6 interactions with the core ORC in the two organisms.
This refined fly model has the unique advantage of having the option to differentially test fly, human, and chimeric Orc6 proteins to uncover rationed and dissimilar highlights of the protein and its function in the cells of metazoan living beings.
Also read: Designing Special RBCs for the delivery of Therapeutic Proteins
Source:
Maxim Balasov et al, Humanized Drosophila Model of the Meier-Gorlin Syndrome Reveals Conserved and Divergent Features of the Orc6 Protein, Genetics (2020). DOI: http://10.1534/genetics.120.303698
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