Saturday, February 23, 2013

Notes for Genetics and Genomics Vol.1


It was so stressed out these days because I was officially trapping in one of the “Kick My Ass” genetics and genomics course. It is my first time to realize that graduate school is going to be tough because of the course titled “ADVANCED”. Anyway, I can make it fun to learn couple of decent genetic findings, as well as many terminologies that I’ve never heard before. So I set up my mind on summarizing the things I learned about genetics for this new post.

Dosage Compensation
It refers to a hypothetical mechanism that balances the expression of X-linked genes between males and females. Dosage compensation varies in different orgasm, but it is ubiquitous in eukaryotes. In human and other mammals, males (XY) express normal level of X-linked genes while in females (XY) one of X chromosome is inactivated. This was found by Ohno S in 1959, by showing two different X-chromosomes of the mammal cells; one is like autosome and the other is condensed and heterochromatic. On the contrary, in Drosophila, it is the female who dominates the gene dosage, so the males double the expression of genes on X-chromosome. As for hermaphrodite C. elegans, both X-chromosomes are somewhat repressed. The following picture shows that Xist RNA is coating only one X-chromosome, which indicates the inactivation of another.



How the Y-chromosome is maintained in human evolution?
Y-chromosome is the most unique, funky and charismatic guy in human males’ karyotype. It stands on its own, being without a homolog to pair with. It is scared by X-chromosome, which may try hard to invade Y by homologue recombination. Y has to make its own way for spermatogenesis. During meiosis, palindrome structures in male-specific region of Y (MSY) are maintained by gene conversion. These palindromes play a big role in protecting Y-chromosome from exchanging sequence with X-chromosome and the subsequent loss of function.

Lange et al investigated the unexpected consequence by maintaining palindromes in MSY and the genetic etiology for Turner’s syndrome. Their model is based on the isodicentric (idic Y) generated during the recombination of sister chromatids of Y by crossover pathway. Idic Y would then lost during the process of spermatogenesis of father’s germline cells, giving a daughter with 45, X0 karyotype. The daughter is diagnosed as Turner syndrome.

This picture shows how idic Y is produced in their model of Turner syndrome






References
Ohno, S. (1969). Evolution of sex chromosomes in mammals. Annual Review of Genetics, 3(1), 495. doi:10.1146/annurev.ge.03.120169.002431
Lange, J. (2009). Isodicentric Y chromosomes and sex disorders as byproducts of homologous recombination that maintains palindromes. Cell, 138(5), 855. doi:10.1016/j.cell.2009.07.042

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