Calico Cats Help Researchers Unlock Mystery of X Chromosome Silencing

Researchers have visualized the inactive chromosomes behind Calico cats' funky fur-color pattern.  The research is expected to better our understanding of human DNA.

The adorable three-color pattern (white, orange and black) in cats is almost exclusively seen in female felines. Other researchers have known since the 1960s that silencing or 'shutting down the activity' of genes in X chromosome is linked with splotchy fur color.

Now, researchers at California San Francisco (UCSF) have visualized the inactivated chromosomes that give rise to this anomaly.

Chromosomes are thread-like structures that carry DNA molecules and proteins. In mammals, sex is determined by two chromosomes- X and Y. Genes present on either of the two chromosomes are called sex-linked genes. Cats have genes associated with fur color on the X chromosome, which is why the splotchy color pattern is seen in females.  

Calico cats have one gene related with orange fur color on one of their X chromosomes and a black fur color gene on the other.

For the study, researchers tried to find a way to see the chromosome in its natural position in the cell.

"A cell's nucleus contains the genetic code, its DNA. But while the structure of the DNA was determined more than 50 years ago, and we're rapidly determining the position of specific genes on chromosomes, no one had visualized the DNA within an intact nucleus-an unfixed, hydrated whole cell," explained Elizabeth Smith from UCSF. "We decided to try."

To see the chromosome, researchers used a new imaging technique called soft x-ray tomography. "We obtained high-resolution, 3-dimensional views of the intact nucleus and, by using a prototype cryo fluorescence microscope along with the x-ray microscope, we were able to identify one specific chromosome, the inactive X chromosome of female cells," Smith said in a news release.

Researchers were able to see various shapes adopted by the silenced X chromosome in different cells. Previously, it was assumed that the inactive chromosomes are tightly packed, which prevents them from being translated into proteins, Livescience reported.

The study will be presented at the at the 58th Annual Biophysical Society Meeting, which takes place Feb. 15-19, 2014, in San Francisco, Calif.

The research could one day help scientists understand the mechanism of sex-linked genetic diseases, Livescience reported.

"The inactivation of one out of two X chromosomes in females is an enormously important epigenetic process," said Smith in the news release. "Uncovering how only one X chromosome is inactivated will help explain the whole process of epigenetic control, meaning the way changes in gene activity can be inherited without changing the DNA code. It can help answer other questions such as if and how traits like obesity can be passed down through generations."