In: Biology
Bushy syndrome (BuS), sometimes referred as Amsterdam dwarfism, is a rare human disease caused by a dominant loss-of-function mutation in any one of at least five different genes, all of which encode components or regulators of the cohesin protein complex. People with BuS have a wide range of morphological abnormalities, including growth retardation, mental impairment and sterility. Analysis of BuS patients shows that in addition to chromosomal mis-segregation during cell division, their abnormal phenotype may be likely due to widespread mis-regulation of gene expression during development. Cohesin may play a role in organizing the chromatin loops necessary for proper regulation of transcription. A. (4 points) In different families, BuS can show an autosomal dominant or X-linked dominant inheritance pattern. How is this possible? What is this an example of? B. (4 points) Explain how a loss-of function allele in a gene encoding the cohesin protein could be dominant to the wild-type allele. C. (4 points) BuS is usually caused by new mutation in one parent's genome. Why? D. (3 points) Explain the general function of the cohesin complex in eukaryotic chromosomes. E. (1 Bonus point) What is the role of shugosin?
A) Bushy syndrome appears when at least one of 5 genes get to loose their function. Some of these genes are located in autosomes, while some are located in the X chromosome, that's why sometimes the disease segregates X-linked and sometimes autosomal dominant.
B) This is a rare condition. This happens when the wildtype allele is not capable of giving the needed gene product, cohesin coplex regulator in this case. The lack of a second copy providing of more regulator affects the complex's effectivity, leading to loss-of function of the whole process.
C) The answer of that is the result of discussi 2 different rates: The mutation rates for this regulatory genes, and the reproduction rates for the affected BuS individuals. This could only occur if the mutation rate is higher than the reproductive rate, and that is the case.
D) Cohesin complex has a major role in sister chromatide segregation during cell division. The complex keeps cohesion between the chromatides, ties them together and stabilizes them so the spindle is able to attach to each one of them properly. Once the spindle is attach and ready to pull, the complex degrades.
E) It protects the cohesin complex from degrading too early in the process.