Question

Bushy syndrome (BuS), sometimes referred as Amsterdam dwarfism, is a 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 Mia-regulation of gene expression during development. Cohesin May play a role in organizing the chromatin loops necessary for proper regulation of transcription.
A) 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) explain how a loss of function allele in a gene encoding the cohesin protein could be dominant to the wild type allele.
C) BuS is usually caused by new mutation in one parents genome. Why?
D) explain the general function of the cohesin complex in eukaryotic chromosomes.
E) what is the role of shugosin?

Answer 1

Amsterdam dwarfism :- it is is named after Dutch pediatrician Cornelia Catharina de Lange, who described it in 1933. It is often termed Brachmann de Lange syndrome or Bushy syndrome. it may be caused by alterations in a cohesin regulatory protein, in human being total five genes are responsible for the formation of cohesin protein complex. out of five two are present on X chromosome and three are present on autosomes.

answer 1:- .Bushy syndrome shows both the pattern of inheritance.

•Bushy syndrome shows a X- Linked dominant inheritance pattern . It is responsible result from the mutation HDAC8 or SMC1A gene. We said it dominant because it is expressed in heterozygous condition [one normal X and one mutated X] in female. Obviously in male there is only one X chromosome so there is always a chance of expression of gene [may be recessive or dominant].

• in another chance, syndrome is caused by mutations in the NIPBL, RAD21, or SMC3 gene, the condition is considered to have an autosomal dominant pattern of inheritance.

2.During normal embryonic development cohesion protein complex plays an important role . It helps regulate the structure and organization of chromosomes, stabilize cells' genetic information, and repair damaged DNA. The cohesin complex also regulates the activity of certain genes that guide the development of limbs, face, and other parts of the body. All five genes [above – X linked HDAC8 , SMC1A and autosomal NIPBL, RAD21, SMC3 ]contribute to the structure or function of the cohesin complex. Mutations in the NIPBL, SMC1A, HDAC8, RAD21, and SMC3 genes cause syndrome by impairing the funrupt the proction of the cohesin complex, which disrupts gene regulation during critical stages of early development.

3.As we see that the cohesion protein is regulated by five genes , any mutational change in any of five is dirupt the production of normal cohesion protein. During gamete formation in both parent [sperm and ova], a newly form mutation in autosomal or x chromosome can inherit he disease in next generation.

4.In normal condition cohesion is a ring complex which helps to bind the sister chromatid with each other during metaphase ensuring that during mitosis (and meiosis), each sister chromatid segregates to opposite poles.

5..Shugoshin :- it is a type of protein domain which is used during mitosis . It is a check point protein which controlthe spindle formation process and attachment of spindle firbers to kinetochore during the process of cell division [metaphase].