The BUB1B gene is associated with autosomal recessive mosaic variegated aneuploidy syndrome (MVA). Additionally, the BUB1B gene has preliminary evidence supporting a correlation with colon cancer.
More than a dozen mutations in the BUB1B gene have been found to cause mosaic variegated aneuploidy (MVA) syndrome type 1. This condition is characterized by cells with abnormal numbers of chromosomes, a situation known as aneuploidy. Affected individuals grow slowly and have an unusually small head size (microcephaly) and an increased risk of developing cancer in childhood.
MVA syndrome type 1 occurs when both copies of the BUB1B gene have mutations. These mutations reduce the amount of BUBR1 protein in cells or impair the protein's ability to function. A shortage of functioning BUBR1 protein leads to errors in the distribution of chromatids during cell division. Without BUBR1 protein, cell division can proceed, even if all the chromatids are not attached to spindle microtubules. Unattached chromatids are not positioned correctly for separation, and the resulting cells have abnormal numbers of chromosomes.
Research suggests that impairment of the process that delays cell division until the correct time underlies the increased risk of cancer in MVA syndrome, although the mechanism is not completely understood. It is also unclear how BUB1B gene mutations or aneuploidy leads to the other features of MVA syndrome. Researchers speculate that the abnormal cells undergo self-destruction (apoptosis). The signs and symptoms of MVA syndrome may be due to the loss of cells from various tissues during early development.
Normal Function of the BUB1B gene:
The BUB1B gene provides instructions for making a protein called BUBR1, which is important for proper chromosome separation during cell division. Before cells divide, they must copy all of their chromosomes. The copied DNA from each chromosome is arranged into two identical structures, called sister chromatids, which are attached to one another during the early stages of cell division. The sets of chromosomes align within the cell, with each chromatid attached to a structure called a spindle microtubule; when all chromatids are correctly attached, the spindle microtubule pulls the two halves of the chromatid pair to opposite sides of the cell. The cell then divides in two such that each new cell contains one complete set of chromosomes.
The BUBR1 protein helps ensure that each sister chromatid is attached to a spindle microtubule. If any chromatids remain unattached, the protein prevents cell division.